| Type |
Details |
Score |
| Protein Domain |
| Name: |
Laminin-type EGF domain |
| Type: |
Domain |
| Description: |
This entry represents the laminin-type EGF-like domain (LE) found in Laminin subunit gamma-1 and Netrin-1 from Homo sapiens and Mus musculus. Laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation [
,
]. They are composed of distinct but related alpha, beta and gamma chains that form a cross-shaped molecule consisting of a long arm and three short globular arms. The long arm has a coiled coil structure contributed by all three chains and cross-linked by interchain disulphide bonds [,
]. Beside the different types of globular domains each subunit contains, in its first half, consecutive repeats of about 60 amino acids in length that include eight conserved cysteines []. The tertiary structure of this domain is remotely similar in its N-terminal to that of the EGF-like module [,
] (see ). The number of copies of the LE domain in the different forms of laminins is highly variable; from 3 up to 22 copies have been found.
A schematic representation of the topology of the four disulphide bonds in the LE domain is shown below.+-------------------+
+-|-----------+ | +--------+ +-----------------+| | | | | | | |
xxCxCxxxxxxxxxxxCxxxxxxxCxxCxxxxxGxxCxxCxxgaagxxxxxxxxxxxCxxsssssssssssssssssssssssssssssssssss
'C': conserved cysteine involved in a disulphide bond'a': conserved aromatic residue
'G': conserved glycine (lower case = less conserved)'s': region similar to the EGF-like domain
Long consecutive arrays of LE domains in laminins form rod-like elements of limited flexibility [
], which determine the spacing in the formation of laminin networks of basement membranes [].Netrins control guidance of the central nervous system commissural axons and peripheral motor axons [
,
,
,
]. This protein also serves as a survival factor via its association with its receptors which prevent the initiation of apoptosis, thus being involved in tumorigenesis [,
]. |
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| Protein Domain |
| Name: |
Tryptophan-tRNA ligase, archaea |
| Type: |
Family |
| Description: |
Tryptophan-tRNA ligases (also known as Tryptophanyl-tRNA synthetases) are widely distributed, being found in archaea, bacteria and eukaryotes. This entry represents an archaeal subgroup of the enzymes. The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [
].The class Ia aminoacyl-tRNA synthetases consist of the isoleucyl, methionyl, valyl, leucyl, cysteinyl, and arginyl-tRNA synthetases; the class Ib include the glutamyl and glutaminyl-tRNA synthetases, and the class Ic are the tyrosyl and tryptophanyl-tRNA synthetases [
]. |
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| Protein Domain |
| Name: |
Alanine-tRNA ligase, archaea |
| Type: |
Family |
| Description: |
Alanine-tRNA ligase (also known as alanyl-tRNA synthetase) (
) is an alpha4 tetramer that belongs to class IIc.
Alanine-tRNA ligase catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). It also edits incorrectly charged Ser-tRNA(Ala) and Gly-tRNA(Ala) via its editing domain.This family of alanine-tRNA ligases is limited to the archaea. The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric [
]. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c []. |
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| Protein Domain |
| Name: |
RNA polymerase sigma-E factor, actinobacteria |
| Type: |
Family |
| Description: |
The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors [
,
]. The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors [
].This group of similar sigma-70 factors includes the sigE factor from Streptomyces coelicolor [
]. The protein appears to include a paralogous expansion in the Streptomycetes lineage, while related Actinomycetales have at most two representatives. |
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| Protein Domain |
| Name: |
RNA polymerase sigma-G type |
| Type: |
Family |
| Description: |
The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors [,
]. The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors [
].Members of this entry comprise the Firmicutes lineage endospore formation-specific sigma factor SigG. It is also designated stage III sporulation protein G (SpoIIIG). Members of this entry are closely related to sigma-F (SpoIIAC), another sporulation sigma factor. |
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| Protein Domain |
| Name: |
Nitrophorin domain |
| Type: |
Domain |
| Description: |
Nitrophorins are haemoproteins found in saliva of blood-feeding insects [
,
]. Saliva of the blood-sucking bug Rhodnius prolixus (Triatomid bug) contains four homologous nitrophorins, designated NP1 to NP4 in order of their relative abundance in the glands []. As isolated, nitrophorins contain nitric oxide (NO) ligated to the ferric (FeIII) haem iron. Histamine, which is released
by the host in response to tissue damage, is another nitrophorin ligand. Nitrophorins transport NO to the feeding site.Dilution, binding of histamine and increase in pH (from pH ~5 in salivary gland to pH ~7.4 in the host tissue) facilitate the release of NO into the tissue where it induces vasodilatation.
The salivary nitrophorin from the hemipteran Cimex lectularius (Bed bug) has no sequence similarity to R. prolixus nitrophorins. It is suggested that the two classes of insect nitrophorins have arisen as a product of the convergent
evolution [].3-D structures of several nitrophorin complexes are known [
]. The nitrophorin structures reveal lipocalin-likeeight-stranded β-barrel, three α-helices and two disulphide bonds, with haem inserted into one end of the barrel. Members of the lipocalin family are known to bind a variety of small hydrophobic ligands, including biliverdin, in a similar fashion (see [
] for review). The haem iron is ligated to His59. The position of His59 is restrained through water-mediatedhydrogen bond to the carboxylate of Asp70. The His59-Fe bond is bent ~15 degrees out of the imidazole plane. Asp70 forms an unusual hydrogen bond with one of the haem propionates, suggesting the residue has an altered pKa. In NP1-histamine
structure, the planes of His59 and histamine imidazole rings lie in an arrangement almost identical to that found in oxidised cytochrome b5.This entry represents the nitrophorin structural domain. |
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| Protein Domain |
| Name: |
RNA polymerase sigma-70 RpoE type |
| Type: |
Family |
| Description: |
The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors [
,
]. The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors [].This entry represents the clade of sigma factors called RpoE. These proteins are variously annotated as sigma-24, sigma-E factor, sigma-H factor, fecI-like sigma factor or alternative sigma factor AlgU. |
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| Protein Domain |
| Name: |
Acetylcholinesterase, tetramerisation domain |
| Type: |
Domain |
| Description: |
Cholinesterase enzymes are members of the broader alpha/beta hydrolase family and can be dividied into two distinct groups: those that catalyse the hydrolysis of acetylcholine to choline and acetate (acetylcholinesterases
)
acetylcholine + H2O ->choline + acetate
and those that catalyse the conversion of other acylcholines to a choline and a weak acid (cholinesterases )
an acylcholine + H2O ->choline + a carboxylate
Acetylcholinesterase also acts on a variety of acetic esters and catalyses transacetylations. It is the most intensively studied of the cholinesterase enzymes due to its key physiological role in the turnover of the neurotransmitter acylcholine [
]. This enzyme is found in, or attached to, cellular or basement membranes of presynaptic cholinergic neurons and postsynaptic cholinoceptive cells within the neuromuscular junction. Signal transmission at the neuromuscular junction involves the release of acylcholine, its interaction with the acycholine receptor and hydrolysis, all occuring in a period of a few milliseconds. Rapid hydrolysis of the newly released aceytlcholine is vital in order to prevent continuous firing of the nerve impulses []. Consistent with its role in this process, acetylcholinesterase has an unusually high turnover number, ensuring that acetylcholine is broken down quickly. There is evidence to suggest that acetylcholinesterase has additional important roles including involvement in neuronal adhesion, the formation of Alzheimer fibrils, and neurite growth [,
,
]. The 3D structure of acetylcholinesterase and a cholinesterase have been determined [
,
]. These proteins share the 3-layer α-β-alpha sandwich fold common to members of the alpha/beta hydrolase family. Surprisingly, given the high turnover number of acetylcholinesterase, the active site of these enzymes is located at the bottom of a deep and narrow cleft, named the active-site gorge.The acetylcholinesterase tetramerisation domain is found at the C terminus and forms a left handed superhelix. |
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| Protein Domain |
| Name: |
Integrin beta-4 subunit |
| Type: |
Family |
| Description: |
Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton and activate many intracellular signalling pathways [
,
]. An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a vWA domain inserted within the integrin domain at the N terminus.Most integrins recognise relatively short peptide motifs, and in general require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits [
]. There are at least 18 types of alpha and 8 types of beta subunits recognised in humans []. Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule []. Each association of alpha and beta subunits has its own binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activate or inhibit another.The beta 4 subunit differs from other beta subunits in three ways: 1) the cytoplasmic domain is larger; 2) it lacks some of the conserved cysteines in the extracellular domain; and 3) it has a unique domain organisation.Integrin alpha-6/beta-4 is a receptor for laminin. It plays a critical structural role in the hemidesmosome of epithelial cells [
]. Integrin beta-4 is required for the regulation of keratinocyte polarity and motility [].For additional information please see [
,
,
,
,
,
,
,
]. |
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| Protein Domain |
| Name: |
Peptidase M20A |
| Type: |
Family |
| Description: |
This entry represents the MEROPS peptidase subfamily M20A (clan MH), which includes human N-fatty-acyl-amino acid synthase/hydrolase PM20D1, Carboxypeptidase S from Saccharomyces cerevisiae and similar eukaryotic and bacterial sequences. PM20D1 is a secreted enzyme that regulates the endogenous N-fatty acyl amino acid (NAAs) tissue and circulating levels by functioning as a bidirectional NAA synthase/hydrolase [
]. Carboxypeptidase S, which is used for certain peptides as sole nitrogen source, has a preference for releasing an amino acid attached to Gly []. The peptidases of this protein family have two catalytic zinc ions at the active site, bound by His/Asp, Asp, Glu, Asp/Glu and His. The catalysed reaction involves the release of an N-terminal amino acid, usually neutral or hydrophobic, from a polypeptide []. Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation which is usually zinc, but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophillic role.
Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site []. The HEXXH motif is relatively common, but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases []. |
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| Protein Domain |
| Name: |
DNA Ligase 4, adenylation domain |
| Type: |
Domain |
| Description: |
DNA ligase (polydeoxyribonucleotide synthase) is the enzyme that joins two DNA fragments by catalysing the formation of an internucleotide ester bond between phosphate and deoxyribose. It is active during DNA replication, DNA repair and DNA recombination. There are two forms of DNA ligase, one requires ATP (
), the other NAD (
), the latter being restricted to eubacteria. Eukaryotic, archaebacterial, viral and some eubacterial DNA ligases are ATP-dependent. The first step in the ligation reaction is the formation of a covalent enzyme-AMP complex. The co-factor ATP is cleaved to pyrophosphate and AMP, with the AMP being covalently joined to a highly conserved lysine residue in the active site of the ligase. The activated AMP residue is then transferred to the 5'phosphate of the nick, before the nick is sealed by phosphodiester-bond formation and AMP elimination [
,
].There are three classes of ATP-dependent DNA ligase in eukaryotic cells (I, III and IV). DNA ligase IV is required for DNA non-homologous end joining pathways, including recombination of the V(D)J immunoglobulin gene segments in cells of the mammalian immune system. DNA ligases have a highly modular architecture consisting of a unique arrangement of two or more discrete domains. The adenylation and C-terminal oligonucleotide/oligosaccharide binding (OB)-fold domains comprise a catalytic core unit that is common to all members of the ATP-dependent DNA ligase family. The adenylation domain binds ATP and contains many of the active-site residues [
,
].DNA ligase 4 is involved in DNA double-strand break repair [
]. In higher eukaryotes it forms a complex with XRCC4, which is responsible for the ligation step during the DNA-PK-dependent non-homologous end joining (D-NHEJ) [,
]. The Ku component of the DNA-PK (DNA-dependent protein kinase) complex contributes to the recruitment of the LIG4-XRCC4 complex at the DNA break site [].This entry represents the adenylation domain found in DNA ligase 4. |
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| Protein Domain |
| Name: |
Conotoxin, delta-type, conserved site |
| Type: |
Conserved_site |
| Description: |
Cone snail toxins, conotoxins, are small peptides with disulphide connectivity,
that target ion-channels or G-protein coupled receptors. Based on the numberand pattern of disulphide bonds and biological activities, conotoxins can be
classified into several families []. Omega and delta families of conotoxinshave a knottin or inhibitor cystine knot scaffold. The knottin scaffold is a
very special disulphide through disulphide knot, in which the III-VI disulphidebond crosses the macrocycle formed by two other disulphide bonds (I-IV and II-
V) and the interconnecting backbone segments, where I-VI indicates the sixcysteine residues starting from the N terminus.
Conotoxins represent a unique arsenal of neuropharmacologically active
peptides that have been evolutionarily tailored to afford unprecedented andexquisite selectivity for a wide variety of ion-channel subtypes. The toxins
derived from cone snails are currently being investigated for the treatment ofchronic pain, epilepsy, cardiovascular diseases, psychiatric and movement
disorders, spasticity, cancer, stroke as well as an anesthetic agent. Severalpotential analgesic and anti-inflammatory peptides from conotoxin family have
been identified and patented [], []:Conus magus (Magus cone) (Magician's cone snail) omega-conotoxin MVIIa (Ziconotide) is used for the treatment of
chronic pain.Conus catus (Cat cone) omega-conotoxin CVID is tested for treating severe morphine-
resistant pain stress.Conus geographus (Geography cone) (Nubecula geographus) omega-conotoxin GVIA may exert antagonistic effects
against beta-endorphin induced anti-nociception.The cysteine arrangement [C-C-CC-C-C] is the same for omega and deltafamilies, but omega conotoxins are calcium channel blockers whereas delta
conotoxins delay the inactivation of sodium channels. The disulphidebonding network as well as specific amino acids in inter-cysteine loops
provide specificity of conotoxin []. Two signature patterns were developedfor omega and delta conotoxin families. The patterns each include six
conserved cysteines thought to be important for the maintenance of thetertiary structure of the conotoxins. This entry represents the delta-conotoxins.
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| Protein Domain |
| Name: |
Conotoxin, omega-type, conserved site |
| Type: |
Conserved_site |
| Description: |
Cone snail toxins, conotoxins, are small neurotoxic peptides with disulphide connectivity that target ion-channels or G-protein coupled receptors. Based on the number and pattern of disulphide bonds and biological activities, conotoxins can be classified into several families [
]. Omega, delta and kappa families of conotoxins have a knottin or inhibitor cysteine knot scaffold. The knottin scaffold is a very special disulphide-through-disulphide knot, in which the III-VI disulphide bond crosses the macrocycle formed by two other disulphide bonds (I-IV and II-V) and the interconnecting backbone segments, where I-VI indicates the six cysteine residues starting from the N terminus.Conotoxins represent a unique arsenal of neuropharmacologically active peptides that have been evolutionarily tailored to afford unprecedented and
exquisite selectivity for a wide variety of ion-channel subtypes. The toxinsderived from cone snails are currently being investigated for the treatment of
chronic pain, epilepsy, cardiovascular diseases, psychiatric and movementdisorders, spasticity, cancer, and stroke, as well as an anesthetic agent. Several potential analgesic and anti-inflammatory peptides from conotoxin family have been identified and patented [
,
]:Conus magus (Magus cone) (Magician's cone snail) omega-conotoxin MVIIa (Ziconotide) is used for the treatment of chronic pain.Conus catus (Cat cone) omega-conotoxin CVID is tested for treating severe morphine-resistant pain stress.Conus geographus (Geography cone) (Nubecula geographus) omega-conotoxin GVIA may exert antagonistic effects against beta-endorphin induced anti-nociception.The cysteine arrangements [C-C-CC-C-C] are the same for the omega and delta families, even though omega conotoxins are calcium channel blockers, whereas delta conotoxins delay the inactivation of sodium channels. The disulphide bonding network as well as specific amino acids in inter-cysteine loops provide the specificity of conotoxins []. Two signature patterns were developed for the omega and delta conotoxin families. The patterns each include six conserved cysteines thought to be important for the maintenance of the tertiary structure of the conotoxins. This entry represents the omega-conotoxins. |
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| Protein Domain |
| Name: |
ATP synthase, F0 complex, subunit D superfamily, mitochondrial |
| Type: |
Homologous_superfamily |
| Description: |
F-ATPases (also known as ATP synthases, F1F0-ATPase, or H(+)-transporting two-sector ATPase) (
) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), with additional subunits in mitochondria. Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the alpha(3)beta(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis [
]. These ATPases can also work in reverse in bacteria, hydrolysing ATP to create a proton gradient.This entry represents subunit D superfamily from the F0 complex in F-ATPases found in mitochondria. The D subunit is part of the peripheral stalk that links the F1 and F0 complexes together, and which acts as a stator to prevent certain subunits from rotating with the central rotary element. The peripheral stalk differs in subunit composition between mitochondrial, chloroplast and bacterial F-ATPases. In mitochondria, the peripheral stalk is composed of one copy each of subunits OSCP (oligomycin sensitivity conferral protein), F6, B and D [
]. There is no homologue of subunit D in bacterial or chloroplast F-ATPase, whose peripheral stalks are composed of one copy of the delta subunit (homologous to OSCP), and two copies of subunit B in bacteria, or one copy each of subunits B and B' in chloroplasts and photosynthetic bacteria. |
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| Protein Domain |
| Name: |
5-Hydroxytryptamine 4 receptor |
| Type: |
Family |
| Description: |
5-hydroxytryptamine (5-HT) or serotonin, is a neurotransmitter that it is primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS). It is implicated in a vast array of physiological and pathophysiological pathways. Receptors for 5-HT mediate both excitatory and inhibitory neurotransmission, and modulate the release of many neurotransmitters including glutamate, GABA, dopamine, epinephrine/norepinephrine, and acetylcholine, as well as many hormones, including oxytocin, prolactin, vasopressin and cortisol. In the CNS, 5-HT receptors can influence various neurological processes, such as aggression, anxiety and appetite and, as a, result are the target of a variety of pharmaceutical drugs, including many antidepressants, antipsychotics and anorectics [
]. The 5-HT receptors are grouped into a number of distinct subtypes, classified according to their antagonist susceptibilities and their affinities for 5-HT. With the exception of the 5-HT3 receptor, which is a ligand-gated ion channel [
], all 5-HT receptors are members of the rhodopsin-like G protein-coupled receptor family [], and they activate an intracellular second messenger cascade to produce their responses. The 5-HT4 receptor functions in both the peripheral and central nervous system, and is involved in modulating the release of various neurotransmitters. In addition to adenylyl cyclase stimulation, direct coupling to potassium channels and voltage sensitive calcium channels have been proposed as postreceptor events [
]. The 5HT4 receptor is located in neurons in the CNS, with highest levels in colliculus [] and hippocampus [,
,
,
], it has not been found in the cerebellum []. In the CNS, the receptor enhances synaptic transmission [], and they may also play a role in learning, memory [,
,
] and appetite []. In the periphery, it is found in the alimentary tract, urinary bladder, heart and adrenal gland [,
,
,
]. |
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| Protein Domain |
| Name: |
Star-PAP, RNA recognition motif |
| Type: |
Domain |
| Description: |
This entry represents the RNA recognition motif (RRM) of Star-PAP (Speckle targeted PIPKIalpha regulated poly (A) polymerase), which is a nuclear non-canonical PAP (Poly(A) polymerase) regulated by lipid second messenger phosphatidyl-inositol-4,5-bisphosphate (PI4,5P2) [
]. As its name suggests, Star-PAP interacts and is regulated by the enzyme phosphatidyl-inositol-4-phosphate-5-kinase type I alpha (PIPKIalpha) that synthesises nuclear PI4,5P2. Star-PAP polyadenylates select subset of mRNAs in the cell involved in oxidative stress response, apoptosis and cancer[
,
,
]. Although it belongs to the well-characterised poly(A) polymerase protein superfamily, Star-PAP is highly divergent from both the poly(A) polymerase (PAP) and the terminal uridylyl transferase (TUTase), identified within the editing complexes of trypanosomes. Star-PAP contains an N-terminal C2H2-type zinc finger motif followed by an RNA recognition motif (RRM), a split PAP domain linked by a proline-rich region, a PAP catalytic and core domain, a PAP-associated domain, an RS repeat, and a nuclear localization signal (NLS).Almost all eukaryotic mRNAs acquire a poly(A) tail at the 3'-end which confers stability and is required for export and translation of the mRNA. Polyadenylation is carried out by a 3'-end processing complex in a two-step reaction: cleavage at the 3'-UTR followed by the addition of poly (A) tail to the cleaved RNA. The canonical PAP, PAPalpha, is the major nuclear PAP is responsible for the general polyadenylation of nuclear pre-mRNAs. However, several non-canonical PAPs have been identified, such as Star-PAP [
]. Interestingly, the mechanism for pre-mRNA cleavage and polyadenylation is different for PAPalpha and Star-PAP. PAPalpha is recruited to UTR RNA by the interaction with CPSF and CstF, while Star-PAP directly binds the target UTR RNA upstream of poly (A) signal (PAS) and recruits the cleavage factor CPSF-160 and CPSF-73 []. |
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| Protein Domain |
| Name: |
DNA nucleotidylexotransferase (TdT) / DNA-directed DNA/RNA polymerase mu |
| Type: |
Family |
| Description: |
DNA carries the biological information that instructs cells how to exist
in an ordered fashion: accurate replication is thus one of the mostimportant events in the cell life cycle. This function is mediated by
DNA-directed DNA-polymerases, which add nucleotide triphosphate (dNTP)residues to the 5'-end of the growing DNA chain, using a complementary
DNA as template. Small RNA molecules are generally used as primers forchain elongation, although terminal proteins may also be used. Three motifs, A, B and C [
], are seen to be conserved across all DNA-polymerases, with motifs A and C also seen in RNA- polymerases. They are centred on invariant residues, and their structural significance was implied from the Klenlow (Escherichia coli) structure: motif A contains a strictly-conserved aspartate at the junction of a β-strand and an α-helix; motif B contains an α-helix with positive charges; and motif C has a doublet of negative charges, located in a β-turn-beta secondary structure [].DNA polymerases (
) can be classified, on the basis of sequence
similarity [,
], into at least four different groups: A, B, C and X. Members of family X are small (about 40 Kd) compared with other polymerases and encompass two distinct polymerase enzymes that have similar functionality: vertebrate polymerase beta (same as Saccharomyces cerevisiae pol 4), and terminal deoxynucleotidyl-transferase (TdT) (). The former functions in DNA repair, while
the latter terminally adds single nucleotides to polydeoxynucleotide chains.Both enzymes catalyse addition of nucleotides in a distributive manner, i.e. they
dissociate from the template-primer after addition of each nucleotide.DNA-polymerases show a degree of structural similarity with RNA-polymerases.
This entry represents terminal deoxynucleotidyl-transferase (TdT) and the DNA-directed DNA/RNA polymerase mu. The latter is a gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining [
,
]. |
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| Protein Domain |
| Name: |
Cytochrome c oxidase-like, subunit I superfamily |
| Type: |
Homologous_superfamily |
| Description: |
Cytochrome c oxidase (
) is a key enzyme in aerobic metabolism. Proton pumping haem-copper oxidases represent the terminal, energy-transfer enzymes of respiratory chains in prokaryotes and eukaryotes. The CuB-haem a3 (or haem o) binuclear centre, associated with the largest subunit I of cytochrome c and ubiquinol oxidases (
), is directly involved in the coupling between dioxygen reduction and proton pumping [
,
].Some terminal oxidases generate a transmembrane proton gradient across the plasma membrane (prokaryotes) or the mitochondrial inner membrane (eukaryotes).
The enzyme complex consists of 3-4 subunits (prokaryotes) up to 13 polypeptides (mammals) of which only the catalytic subunit (equivalent to mammalian subunit I (CO I) is found in all haem-copper respiratory oxidases. The presence of a bimetallic centre (formed by a high-spin haem and copper B) as well as a low-spin haem, both ligated to six conserved histidine residues near the outer side of four transmembrane spans within CO I is common to all family members [
,
,
]. In contrast to eukaryotes the respiratory chain of prokaryotes is branched to multiple terminal oxidases. The enzyme complexes vary in haem and copper composition, substrate type and substrate affinity. The different respiratory oxidases allow the cells to customize their respiratory systems according to a variety of environmental growth conditions []. It has been shown that eubacterial quinol oxidase was derived from cytochrome c oxidase in Gram-positive bacteria and that archaebacterial quinol oxidase has an independent origin. A considerable amount of evidence suggests that proteobacteria (Purple bacteria) acquired quinol oxidase through a lateral gene transfer from Gram-positive bacteria [
].This entry represents a structural domain superfamily found in subunit I of cytochrome c oxidase as well as related proteins, including quinol oxidase. Structurally, it is composed of twelve transmembrane helices in an approximate threefold rotational symmetric arrangement. |
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| Protein Domain |
| Name: |
Acetylcholinesterase, insect |
| Type: |
Family |
| Description: |
Cholinesterase enzymes are members of the broader alpha/beta hydrolase family and can be dividied into two distinct groups: those that catalyse the hydrolysis of acetylcholine to choline and acetate (acetylcholinesterases
)
acetylcholine + H2O ->choline + acetate
and those that catalyse the conversion of other acylcholines to a choline and a weak acid (cholinesterases )
an acylcholine + H2O ->choline + a carboxylate
Acetylcholinesterase also acts on a variety of acetic esters and catalyses transacetylations. It is the most intensively studied of the cholinesterase enzymes due to its key physiological role in the turnover of the neurotransmitter acylcholine [
]. This enzyme is found in, or attached to, cellular or basement membranes of presynaptic cholinergic neurons and postsynaptic cholinoceptive cells within the neuromuscular junction. Signal transmission at the neuromuscular junction involves the release of acylcholine, its interaction with the acycholine receptor and hydrolysis, all occuring in a period of a few milliseconds. Rapid hydrolysis of the newly released aceytlcholine is vital in order to prevent continuous firing of the nerve impulses []. Consistent with its role in this process, acetylcholinesterase has an unusually high turnover number, ensuring that acetylcholine is broken down quickly. There is evidence to suggest that acetylcholinesterase has additional important roles including involvement in neuronal adhesion, the formation of Alzheimer fibrils, and neurite growth [,
,
]. The 3D structure of acetylcholinesterase and a cholinesterase have been determined [
,
]. These proteins share the 3-layer α-β-alpha sandwich fold common to members of the alpha/beta hydrolase family. Surprisingly, given the high turnover number of acetylcholinesterase, the active site of these enzymes is located at the bottom of a deep and narrow cleft, named the active-site gorge.Insect acetylcholinesterase
is often targeted by insecticides,especially in the effort to eradicate mosquitos from certain
areas of the world []. |
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| Protein Domain |
| Name: |
Alanine racemase |
| Type: |
Family |
| Description: |
Alanine racemase catalyses the pyridoxal-dependent conversion of L-alanine into D-alanine, a key
component of bacterial peptidoglycan []. In Escherichia coli and Salmonella typhimurium, there are two alanine racemase isoforms, alr is a biosynthetic form required for cell wall formation; and dadB
functions in L-alanine catabolism. By contrast with dadB and alr, both of which are monomeric enzymes, the alanine racemase of Bacillaceae are homodimers. In Pseudomonas putida, a broad-specificity
amino acid racemase is structurally and functionally related to alanine racemase. The 3D-structure of the dimeric alanine racemase from Bacillus stearothermophilus has been determined to a resolution of
1.9 A []. Each monomer comprises two domains, with an eight-stranded alpha/beta barrel at the N terminus, and a C-terminal β-strand domain. In the dimer, the mouth of the alpha/beta
barrel of one monomer faces the second domain of the other monomer. The pyridoxal 5'-phosphate (PLP) cofactor lies in and above the barrel mouth and is covalently linked via an aldimine linkage
to Lys39. Several other residues are involved in anchoring the PLP, for example, Arg219 forms a hydrogen bond with the pyridine nitrogen of the cofactor, which is assumed to influence electron
delocalisation in PLP-alanine intermediates; Arg136 donates a hydrogen bond to the phenolic oxygen of PLP, and may be involved in substrate binding and stabilisation of intermediates; and Tyr265'
is postulated to be a 2 proton donor to the carbanion intermediate [].A particular case is represented by Enterococcus VanT, which has both serine and alanine racemase activities, although it is able to racemize serine more efficiently than alanine. Unlike other alanine and serine racemases, VanT is a transmembrane protein. At least ten transmembrane helices are predicted to be present in the N-terminal domain [
] and the C-terminal domain has structural homology with the alanine racemase [] and it is matched by this entry. |
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| Protein Domain |
| Name: |
Carboxypeptidase B, carboxypeptidase domain |
| Type: |
Domain |
| Description: |
This entry represents the carboxypeptidase domain found in carboxypeptidase B-like peptidases. Carboxypeptidase B (CPB; MEROPS identifier M14.003) belongs to subfamily M14A (A/B subfamily) of the M14 family of metallocarboxypeptidases (MCPs) [
]. Carboxypeptidase B (CPB) releases the basic residues lysine or arginine []. A/B subfamily enzymes are normally synthesized as inactive precursors containing a signal peptide, followed by a globular N-terminal pro-region linked to the enzyme; these proenzymes are called procarboxypeptidases []. Procarboxypeptidase B (PCPB) is produced by the exocrine pancreas and stored as a stable zymogen in the pancreatic granules until secretion into the digestive tract occurs where it is activated by trypsin []. PCPB has been reported to be a good serum marker for the diagnosis of acute pancreatitis and graft rejection in pancreas transplant recipients [].The carboxypeptidase A family can be divided into four subfamilies: M14A
(carboxypeptidase A or digestive), M14B (carboxypeptidase H or regulatory), M14C (gamma-D-glutamyl-L-diamino acid peptidase I) and M14D (AGTPBP-1/Nna1-like proteins) [,
]. Members of subfamily M14B have longer C-termini than those of subfamily M14A [], and carboxypeptidase M (a member of the H family) is bound to the membrane by a glycosylphosphatidylinositol anchor, unlike the majority of the M14 family, which are soluble []. The zinc ligands have been determined as two histidines and a glutamate,and the catalytic residue has been identified as a C-terminal glutamate,
but these do not form the characteristic metalloprotease HEXXH motif [,
]. Members of the carboxypeptidase A family are synthesised as inactive molecules with propeptides that must be cleaved to activate the enzyme. Structural studies of carboxypeptidases A and B reveal the propeptide to exist as a globular domain, followed by an extended α-helix; this shields the catalytic site, without specifically binding to it, while the substrate-binding site is blocked by making specific contacts [,
]. |
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| Protein Domain |
| Name: |
Brain-derived neurotrophic factor |
| Type: |
Family |
| Description: |
During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells [
]. Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF), which is involved in the survival of some classes of embryonic neuron (e.g., peripheral sympathetic neurons) []. NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown []; it has also been found in several snake venoms [,
]. Proteins similar to NGF include brain-derived neurotrophic factor (BDNF) and neurotrophins 3 to 7, all of which demonstrate neuron survival and outgrowth activities. Originally purified from pig brain [
], the neurotrophin BDNF is expressed in a range of tissues and cell types in the CNS and periphery. It exerts its effects by binding to neurotrophic tyrosine kinase receptor type 2 (NTRK2; also called TrkB) and the low affinity nerve growth factor receptor, p75NTR. While the former receptor mediates the neurotrophin's prosurvival functions, activation of p75NTR by BDNF has been shown to promote apoptosis and to inhibit axonal growth []. BDNF is a key regulator of synaptic plasticity, and plays an important role in learning and memory [
]. Several lines of evidence suggest that it is also involved in the control of food intake and body weight []. A number of clinical studies have demonstrated an association between aberrant BDNF levels and disorders and disease states, such as depression, epilepsy, bipolar disorder, Parkinson's disease and Alzheimer's disease []. |
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| Protein Domain |
| Name: |
P2X5 purinoceptor |
| Type: |
Family |
| Description: |
P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional [
]. These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo- and hetero multimers in vivo [
,
]. Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation []. The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies.The P2X5 receptor (along with P2X2, P2X4 and P2X6) falls into a group of
receptors that are sensitive to ATP, but not alphabetamethyleneATP. Splicevariants of P2X5 have been detected [
]. |
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| Protein Domain |
| Name: |
P2X1 purinoceptor |
| Type: |
Family |
| Description: |
P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional [
]. These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo- and hetero multimers in vivo [
,
]. Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation []. The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies.Expression of P2X1 receptors produces receptors that are equally well activated by alphabetamethyleneATP and ATP. The properties of the currents so generated are quite comparable to those determined for native P2X receptors, such as those found to be present in smooth muscle [
]. |
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| Protein Domain |
| Name: |
P2X3 purinoceptor |
| Type: |
Family |
| Description: |
P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional [
]. These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo- and hetero multimers in vivo [
,
]. Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation []. The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies.When expressed, P2X3 receptors (like P2X1 receptors) are found to be equally well activated by alphabetamethyleneATP and ATP. P2X3 receptors desensitise rapidly, with the decay being best-fit by two exponentials, with time constants of ~50 and 300 ms [
]. |
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| Protein Domain |
| Name: |
Peroxisome proliferator-activated receptor |
| Type: |
Family |
| Description: |
Steroid or nuclear hormone receptors (NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members of the superfamily include the steroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands [
]. The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner [,
]. In addition to C-terminal ligand-binding domains, these nuclear receptors contain a highly-conserved, N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes, hormone resistance syndromes, etc. While several NRs act as ligand-inducible transcription factors, many do not yet have a defined ligand and are accordingly termed 'orphan' receptors. During the last decade, more than 300 NRs have been described, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members.Peroxisome proliferator-activated receptors (PPAR) are ligand-activated
transcription factors that belong to the nuclear hormone receptor superfamily. Three cDNAs encoding PPARs have been isolated from Xenopus laevis: xPPAR alpha, beta and gamma []. All three xPPARs appear to be activated by both synthetic peroxisome proliferators and naturally occurring fatty acids, suggesting a common mode of action for all members of this subfamily of receptors []. Furthermore, the multiplicity of the receptors suggests the existence of hitherto unknown cellular signalling pathways for xenobiotics and putative endogenous ligands []. Synonym(s): 1C nuclear receptor |
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| Protein Domain |
| Name: |
Nuclear receptor ROR |
| Type: |
Family |
| Description: |
Steroid or nuclear hormone receptors (NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members of the superfamily include the steroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands [
]. The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner [,
]. In addition to C-terminal ligand-binding domains, these nuclear receptors contain a highly-conserved, N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes, hormone resistance syndromes, etc. While several NRs act as ligand-inducible transcription factors, many do not yet have a defined ligand and are accordingly termed 'orphan' receptors. During the last decade, more than 300 NRs have been described, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members.Retinoic acid-related orphan receptors (RORs) are orphan NRs related to retinoic acid receptors and include ROR-alpha, ROR-beta and ROR-gamma, which are also referred to as RORA, RORB and RORC. ROR-alpha, ROR-beta and ROR-gamma regulate circadian rhythms with ROR-alpha playing the central role [
]. ROR-alpha has a key role in the development of the cerebellum. ROR-beta is necessary for the proliferation and differentiation of retinal cells. ROR-gamma is required for lymph-node organogenesis [
]. |
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| Protein Domain |
| Name: |
Quinohemoprotein amine dehydrogenase, alpha subunit, haem binding domain |
| Type: |
Domain |
| Description: |
Quinohemoprotein amine dehydrogenases (QHNDH)
) are enzymes produced in the periplasmic space of certain Gram-negative bacteria, such as Paracoccus denitrificans and Pseudomonas putida, in response to primary amines, including n-butylamine and benzylamine. QHNDH catalyses the oxidative deamination of a wide range of aliphatic and aromatic amines through formation of a Schiff-base intermediate involving one of the quinone O atoms [
]. Catalysis requires the presence of a novel redox cofactor, cysteine tryptophylquinone (CTQ). CTQ is derived from the post-translational modification of specific residues, which involves the oxidation of the indole ring of a tryptophan residue to form tryptophylquinone, followed by covalent cross-linking with a cysteine residue []. There is one CTQ per subunit in QHNDH. In addition to CTQ, two haem c cofactors are present in QHNDH that mediate the transfer of the substrate-derived electrons from CTQ to an external electron acceptor, cytochrome c-550 [,
].QHNDH is a heterotrimer of alpha, beta and gamma subunits. The alpha and beta subunits contain signal peptides necessary for the translocation of QHNDH to the periplasm. The alpha subunit is composed of four domains - domain 1 forming a dihaem cytochrome, and domains 2-4 forming antiparallel β-barrel structures; the beta subunit is a 7-bladed β-propeller that provides part of the active site; and the small, catalytic gamma subunit contains the novel cross-linked CTQ cofactor, in addition to additional thioester cross-links between Cys and Asp/Glu residues that encage CTQ. The gamma subunit assumes a globular secondary structure with two short α-helices having many turns and bends [
]. This entry represents the dihaem cytochrome c domain of the QHNDH alpha subunit. The domain contain two cysteine residues that are involved in thioether linkages to haem [
]. |
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| Protein Domain |
| Name: |
Chloride channel, core |
| Type: |
Homologous_superfamily |
| Description: |
Chloride channels (CLCs) constitute an evolutionarily well-conserved family of voltage-gated channels that are structurally unrelated to the other known voltage-gated channels. They are found in organisms ranging from bacteria to yeasts and plants, and also to animals. Their functions in higher animals likely include the regulation of cell volume, control of electrical excitability and trans-epithelial transport [
].The first member of the family (CLC-0) was expression-cloned from the electric organ of Torpedo marmorata [
], and subsequently nine CLC-like proteins have been cloned from mammals. They are thought to function as multimers of two or more identical or homologous subunits, and they have varying tissue distributions and functional properties. To date, CLC-0, CLC-1, CLC-2, CLC-4 and CLC-5 have been demonstrated to form functional Cl- channels; whether the remaining isoforms do so is either contested or unproven. One possible explanation for the difficulty in expressing activatable Cl- channels is that some of the isoforms may function as Cl- channels of intracellular compartments, rather than of the plasma membrane. However, they are all thought to have a similar transmembrane (TM) topology, initial hydropathy analysis suggesting 13 hydrophobic stretches long enough to form putative TM domains []. Recently, the postulated TM topology has been revised, and it now seems likely that the CLCs have 10 (or possibly 12) TM domains, with both N- and C-termini residing in the cytoplasm [].A number of human disease-causing mutations have been identified in the genes encoding CLCs. Mutations in CLCN1, the gene encoding CLC-1, the major skeletal muscle Cl- channel, lead to both recessively and dominantly-inherited forms of muscle stiffness or myotonia [
]. Similarly, mutations in CLCN5, which encodes CLC-5, a renal Cl- channel, lead to several forms of inherited kidney stone disease []. These mutations have been demonstrated to reduce or abolish CLC function.This superfamily represents the core domain of the cholide ion channel. |
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| Protein Domain |
| Name: |
Chloride channel, voltage gated |
| Type: |
Family |
| Description: |
Chloride channels (CLCs) constitute an evolutionarily well-conserved family of voltage-gated channels that are structurally unrelated to the other known voltage-gated channels. They are found in organisms ranging from bacteria to yeasts and plants, and also to animals. Their functions in higher animals likely include the regulation of cell volume, control of electrical excitability and trans-epithelial transport [
].The first member of the family (CLC-0) was expression-cloned from the electric organ of Torpedo marmorata [
], and subsequently nine CLC-like proteins have been cloned from mammals. They are thought to function as multimers of two or more identical or homologous subunits, and they have varying tissue distributions and functional properties. To date, CLC-0, CLC-1, CLC-2, CLC-4 and CLC-5 have been demonstrated to form functional Cl- channels; whether the remaining isoforms do so is either contested or unproven. One possible explanation for the difficulty in expressing activatable Cl- channels is that some of the isoforms may function as Cl- channels of intracellular compartments, rather than of the plasma membrane. However, they are all thought to have a similar transmembrane (TM) topology, initial hydropathy analysis suggesting 13 hydrophobic stretches long enough to form putative TM domains []. Recently, the postulated TM topology has been revised, and it now seems likely that the CLCs have 10 (or possibly 12) TM domains, with both N- and C-termini residing in the cytoplasm [].A number of human disease-causing mutations have been identified in the genes encoding CLCs. Mutations in CLCN1, the gene encoding CLC-1, the major skeletal muscle Cl- channel, lead to both recessively and dominantly-inherited forms of muscle stiffness or myotonia [
]. Similarly, mutations in CLCN5, which encodes CLC-5, a renal Cl- channel, lead to several forms of inherited kidney stone disease []. These mutations have been demonstrated to reduce or abolish CLC function. |
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| Protein Domain |
| Name: |
Condensin II complex subunit H2, N-terminal |
| Type: |
Domain |
| Description: |
This entry represents the N-terminal domain of the H2 subunit of the condensing II complex, found in eukaryotes but not in fungi. Eukaryotes carry at least two condensin complexes, I and II, each made up of five subunits. The functions of the two complexes are collaborative but non-overlapping. CI appears to be functional in G2 phase in the cytoplasm beginning the process of chromosomal lateral compaction while the CII is concentrated in the nucleus, possibly to counteract the activity of cohesion at this stage. In prophase, CII contributes to axial shortening of chromatids while CI continues to bring about lateral chromatid compaction, during which time the sister chromatids are joined centrally by cohesins. There appears to be just one condensin complex in fungi. CI and CII each contain SMC2 and SMC4 (structural maintenance of chromosomes) subunits, then CI has non-SMC CAP-D2 (CND1), CAP-G (CND3), and CAP-H (CND2). CII has, in addition to the two SMCs, CAP-D3, CAPG2 and CAP-H2. All four of the CAP-D and CAP-G subunits have degenerate HEAT repeats, whereas the CAP-H are kleisins or SMC-interacting proteins (ie they bind directly to the SMC subunits in the complex). The SMC molecules are each long with a small hinge-like knob at the free end of a longish strand, articulating with each other at the hinge. Each strand ends in a knob-like head that binds to one or other end of the CAP-H subunit. The HEAT-repeat containing D and G subunits bind side-by-side between the ends of the H subunit. Activity of the various parts of the complex seem to be triggered by extensive phosphorylations, eg, entry of the complex, in Sch.pombe, into the nucleus during mitosis is promoted by Cdk1 phosphorylation of SMC4/Cut3; and it has been shown that Cdk1 phosphorylates CAP-D3 at Thr1415 in He-La cells thus promoting early stage chromosomal condensation by CII [
,
]. |
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| Protein Domain |
| Name: |
DNA ligase, ATP-dependent, conserved site |
| Type: |
Conserved_site |
| Description: |
DNA ligase (polydeoxyribonucleotide synthase) is the enzyme that joins two DNA fragments by catalysing the formation of an internucleotide ester bond between phosphate and deoxyribose. It is active during DNA replication, DNA repair and DNA recombination. There are two forms of DNA ligase, one requires ATP (
), the other NAD (
), the latter being restricted to eubacteria. Eukaryotic, archaebacterial, viral and some eubacterial DNA ligases are ATP-dependent. The first step in the ligation reaction is the formation of a covalent enzyme-AMP complex. The co-factor ATP is cleaved to pyrophosphate and AMP, with the AMP being covalently joined to a highly conserved lysine residue in the active site of the ligase. The activated AMP residue is then transferred to the 5'phosphate of the nick, before the nick is sealed by phosphodiester-bond formation and AMP elimination [
,
].Vertebrate cells encode three well-characterised DNA ligases (DNA ligases I, III and IV), all of which are related in structure and sequence. With the exception of the atypically small PBCV-1 viral enzyme, two regions of primary sequence are common to all members of the family. The catalytic region comprises six conserved sequence motifs (I, III, IIIa, IV, V-VI), motif I includes the lysine residue that is adenylated in the first step of the ligation reaction. The function of the second, less well-conserved region is unknown. When folded, each protein comprises of two distinct sub-domains: a large amino-terminal sub-domain ('domain 1') and a smaller carboxy-terminal sub-domain ('domain 2'). The ATP-binding site of the enzyme lies in the cleft between the two sub-domains. Domain 1 consists of two antiparallel beta sheets flanked by alpha helices, whereas domain 2 consists of a five-stranded beta barrel and a single alpha helix, which form the oligonucleotide-binding fold [
,
]. |
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| Protein Domain |
| Name: |
DNA ligase, ATP-dependent |
| Type: |
Family |
| Description: |
DNA ligase (polydeoxyribonucleotide synthase) is the enzyme that joins two DNA fragments by catalysing the formation of an internucleotide ester bond between phosphate and deoxyribose. It is active during DNA replication, DNA repair and DNA recombination. There are two forms of DNA ligase, one requires ATP (
), the other NAD (
), the latter being restricted to eubacteria. Eukaryotic, archaebacterial, viral and some eubacterial DNA ligases are ATP-dependent. The first step in the ligation reaction is the formation of a covalent enzyme-AMP complex. The co-factor ATP is cleaved to pyrophosphate and AMP, with the AMP being covalently joined to a highly conserved lysine residue in the active site of the ligase. The activated AMP residue is then transferred to the 5'phosphate of the nick, before the nick is sealed by phosphodiester-bond formation and AMP elimination [
,
].Vertebrate cells encode three well-characterised DNA ligases (DNA ligases I, III and IV), all of which are related in structure and sequence. With the exception of the atypically small PBCV-1 viral enzyme, two regions of primary sequence are common to all members of the family. The catalytic region comprises six conserved sequence motifs (I, III, IIIa, IV, V-VI), motif I includes the lysine residue that is adenylated in the first step of the ligation reaction. The function of the second, less well-conserved region is unknown. When folded, each protein comprises of two distinct sub-domains: a large amino-terminal sub-domain ('domain 1') and a smaller carboxy-terminal sub-domain ('domain 2'). The ATP-binding site of the enzyme lies in the cleft between the two sub-domains. Domain 1 consists of two antiparallel beta sheets flanked by alpha helices, whereas domain 2 consists of a five-stranded beta barrel and a single alpha helix, which form the oligonucleotide-binding fold [
,
]. |
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| Protein Domain |
| Name: |
Isoleucine-tRNA ligase |
| Type: |
Family |
| Description: |
Isoleucine-tRNA ligase (also known as Isoleucyl-tRNA synthetase)(
) is an alpha monomer that belongs to class Ia. The enzyme, isoleucine-tRNA ligase, activates not only the cognate substrate L-isoleucine but also the minimally distinct L-valine in the first, aminoacylation step. Then, in a second, "editing"step, the ligase itself rapidly hydrolyses only the valylated products [
,
] as shown from the crystal structures. The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c []. |
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| Protein Domain |
| Name: |
Liver X receptor |
| Type: |
Family |
| Description: |
Steroid or nuclear hormone receptors (NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members of the superfamily include the steroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands [
]. The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner [,
]. In addition to C-terminal ligand-binding domains, these nuclear receptors contain a highly-conserved, N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes, hormone resistance syndromes, etc. While several NRs act as ligand-inducible transcription factors, many do not yet have a defined ligand and are accordingly termed 'orphan' receptors. During the last decade, more than 300 NRs have been described, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members.Liver X receptors (LXRs) are nuclear receptors that regulate the metabolism of several important lipids, including oxysterols [
]. There are two LXR isoforms, termed alpha and beta, which, upon activation, form heterodimers with retinoid X receptors and bind to an LXR response element found in the promoter region of their target genes. In addition to their involvement in lipid metabolism, LXRs also act as key regulators of macrophage function, and have roles in inflammation and immunity []. |
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| Protein Domain |
| Name: |
Nuclear receptor subfamily 0 group B member 1/2 |
| Type: |
Family |
| Description: |
NR0B1 (also known as DAX-1) is an orphan nuclear receptor involved in the development and maintenance of the steroid hormone pathway. It also plays a role in the development of the embryo and maintenance of pluripotent embryonic stem cells [
]. Mutations of the DAX-1 gene cause X-linked adrenal hypoplasia congenita (XL-AHC), a developmental disorder of the adrenal gland that results in profound hormonal deficiencies and is lethal if untreated [].NR0B2 lacks a conventional DNA binding domain (DBD) and represses the transcriptional activity of various nuclear receptors
[].Steroid or nuclear hormone receptors (NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members of the superfamily include the steroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands [
]. The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner [,
]. In addition to C-terminal ligand-binding domains, these nuclear receptors contain a highly-conserved, N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes, hormone resistance syndromes, etc. While several NRs act as ligand-inducible transcription factors, many do not yet have a defined ligand and are accordingly termed 'orphan' receptors. During the last decade, more than 300 NRs have been described, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members. |
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| Protein Domain |
| Name: |
Alpha-amylase, thermostable |
| Type: |
Family |
| Description: |
O-Glycosyl hydrolases (
) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [
,
]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.
Alpha-amylase is classified as family 13 of the glycosyl hydrolases and is present in archaea, bacteria, plants and animals. Alpha-amylase is an essential enzyme in alpha-glucan metabolism, acting to catalyse the hydrolysis of alpha-1,4-glucosidic bonds of glycogen, starch and related polysaccharides. Although all alpha-amylases possess the same catalytic function, they can vary with respect to sequence. In general, they are composed of three domains: a TIM barrel containing the active site residues and chloride ion-binding site (domain A), a long loop region inserted between the third beta strand and the α-helix of domain A that contains calcium-binding site(s) (domain B), and a C-terminal β-sheet domain that appears to show some variability in sequence and length between amylases (domain C) [
]. Amylases have at least one conserved calcium-binding site, as calcium is essential for the stability of the enzyme. The chloride-binding functions to activate the enzyme, which acts by a two-step mechanism involving a catalytic nucleophile base (usually an Asp) and a catalytic proton donor (usually a Glu) that are responsible for the formation of the beta-linked glycosyl-enzyme intermediate. This entry represents a subfamily of alpha-amylase proteins that are highly thermostable. Studies on amylases with different thermostabilities have revealed several structural and dynamic features that can affect thermal adaptation [
]. One of these features is the number of calcium-binding sites that the enzyme contains, with extra calcium-binding sites contributing to structural stability [,
]. |
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| Protein Domain |
| Name: |
Pancreatic hormone-like |
| Type: |
Family |
| Description: |
Pancreatic hormone (PP) [
] is a peptide synthesized in pancreatic islets of Langherhans, which acts as a regulator of pancreatic and gastrointestinal functions.The hormone is produced as a larger propeptide, which is enzymatically cleaved to yield the mature active peptide: this is 36 amino acids in length [
] and has an amidated C terminus []. The hormone has a globular structure, residues 2-8 forming a left-handed poly-proline-II-like helix, residues 9-13 a beta turn, and 14-32 an α-helix, held close to the first helix by hydrophobic interactions []. Unlike glucagon, another peptide hormone, the structure of pancreatic peptide is preserved in aqueous solution []. Both N and C termini are required for activity: receptor binding and activation functions may reside in the N and C termini respectively [].Pancreatic hormone is part of a wider family of active peptides that includes:Neuropeptide Y (NPY or melanostatin) [
], one of the most abundant peptides in the mammalian nervous system. NPY is implicated in the control of feeding and thesecretion of the gonadotropin-releasing hormone.
Peptide YY (PYY) [
]. PPY is a gut peptide that inhibits exocrine pancreatic secretion, has a vasoconstrictor action and inhibits jejunal and colonic mobility. Known as goannatyrotoxin-Vere1 in the venom of the pygmy desert monitor lizard (Varanus eremius) where it has a triphasic action: rapid biphasic hypertension followed by prolonged hypotension in prey animals [].Various NPY and PYY-like polypeptides from fish and amphibians [
,
].Neuropeptide F (NPF) from invertebrates such as worms and snail.Skin peptide Tyr-Tyr (SPYY) from the frog Phyllomedusa bicolor. SPYY shows a large spectra of antibacterial and antifungal activity.Polypeptide MY (peptide methionine-tyrosine). A regulatory peptide from the intestine of the sea lamprey (Petromyzon marinus) [
].All these peptides are 36 to 39 amino acids long. Like most active peptides, their C-terminal is amidated and they are synthesized as larger protein precursors. |
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| Protein Domain |
| Name: |
Nitrophorin |
| Type: |
Family |
| Description: |
Nitrophorins are haemoproteins found in saliva of blood-feeding insects [
,
]. Saliva of the blood-sucking bug Rhodnius prolixus (Triatomid bug) contains four homologous nitrophorins, designated NP1 to NP4 in order of their relative abundance in the glands []. As isolated, nitrophorins contain nitric oxide (NO) ligated to the ferric (FeIII) haem iron. Histamine, which is releasedby the host in response to tissue damage, is another nitrophorin ligand. Nitrophorins transport NO to the feeding site.
Dilution, binding of histamine and increase in pH (from pH ~5 in salivary gland to pH ~7.4 in the host tissue) facilitate the release of NO into the tissue where it induces vasodilatation.The salivary nitrophorin from the hemipteran Cimex lectularius (Bed bug) has no sequence similarity to R. prolixus nitrophorins. It is suggested that the two classes of insect nitrophorins have arisen as a product of the convergent
evolution [].3-D structures of several nitrophorin complexes are known [
]. The nitrophorin structures reveal lipocalin-likeeight-stranded β-barrel, three α-helices and two disulphide bonds, with haem inserted into one end of the barrel. Members of the lipocalin family are known to bind a variety of small hydrophobic ligands, including biliverdin, in a similar fashion (see [
] for review). The haem iron is ligated to His59. The position of His59 is restrained through water-mediatedhydrogen bond to the carboxylate of Asp70. The His59-Fe bond is bent ~15 degrees out of the imidazole plane. Asp70 forms an unusual hydrogen bond with one of the haem propionates, suggesting the residue has an altered pKa. In NP1-histamine
structure, the planes of His59 and histamine imidazole rings lie in an arrangement almost identical to that found in oxidised cytochrome b5.This entry represents the nitrophorin family. |
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| Protein Domain |
| Name: |
Fas receptor |
| Type: |
Family |
| Description: |
Like all apoptotic cell death, T cell receptor (TCR)-mediated death can be
divided into two phases: an inductive phase and an effector phase. The effector phase includes a sequence of steps that are common to apoptosis in
many cell types, which, if not interrupted, will lead to cell death. Theinduction phase, which often requires the expression of new genes, consists
of a set of signals that activate the effector phase. Outside the thymus,most, if not all, of the TCR-mediated apoptosis of mature T cells (sometimes
referred to as activation-induced cell death (AICD)) is induced through thesurface antigen Fas pathway: activation through the TCR induces expression
of the Fas (CD95) ligand (FasL); the expression of FasL on either aneighbouring cell, or on the Fas-bearing cell, induces trimerisation of Fas,
which then initiates a signal-transduction cascade, leading to apoptosis of the Fas-bearing cell. This commitment stage requires the activation of key
death-inducing enzymes, termed caspases, which act by cleaving proteins that are essential for cell survival and proliferation
[,
].Fas is also known to be essential in the death of hyperactivated peripheral
CD4+ cells: in the absence of Fas, mature peripheral T cells do not die, butthe activated cells continue to proliferate, producing cytokines that lead
to grossly enlarged lymph nodes and spleen. Fas belongs to the tumournecrosis factor receptor (TNFR) family of cysteine-rich type I membrane
receptors; its ligand (FasL) is expressed on activated lymphocytes, NK cells,platelets, certain immune-privileged cells and some tumour cells [
,
].Defects in the Fas-FasL system are associated with various disease syndromes.
Mice with non-functional Fas or FasL display characteristics of lympho-proliferative disorder, such as lymphadenopathy, splenomegaly, and elevated secretion of IgM and IgG. These mice also secrete anti-DNA autoantibodies
and rheumatoid factor []. |
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| Protein Domain |
| Name: |
Nitrile hydratase alpha subunit /Thiocyanate hydrolase gamma subunit |
| Type: |
Family |
| Description: |
Nitrile hydratases (
) are bacterial enzymes that catalyse the hydration of nitrile compounds to the corresponding amides. They are used as biocatalysts in acrylamide production, one of the few commercial scale bioprocesses, as well as in environmental remediation for the removal of nitriles from waste streams. Nitrile hydratases are composed of two subunits, alpha and beta, and are normally active as a tetramer, alpha(2)beta(2). Nitrile hydratases contain either a non-haem iron or a non-corrinoid cobalt centre, both types sharing a highly conserved peptide sequence in the alpha subunit (CXLCSC) that provides all the residues involved in coordinating the metal ion. Each type of nitrile hydratase specifically incorporated its metal with the help of activator proteins encoded by flanking regions of the nitrile hydratase genes that are necessary for metal insertion. The Fe-containing enzyme is photo-regulated: in the dark the enzyme is inactivated due to the association of nitric oxide (NO) to the iron, while in the light the enzyme is active by photo-dissociation of NO. The NO is held in place by a claw setting formed through specific oxygen atoms in two modified cysteines and a serine residue in the active site [
,
]. The cobalt-containing enzyme is unaffected by NO, but was shown to undergo a similar effect with carbon monoxide [,
]. Fe- and cobalt-containing enzymes also display different inhibition patterns with nitrophenols.Thiocyanate hydrolase (SCNase) is a cobalt-containing metalloenzyme with a cysteine-sulphinic acid ligand that hydrolyses thiocyanate to carbonyl sulphide and ammonia [
].The two enzymes, nitrile hydratase and SCNase, are homologous over regions corresponding to almost the entire coding regions of the genes: the beta and alpha subunits of thiocyanate hydrolase were homologous to the amino- and carboxyl-terminal halves of the beta subunit of nitrile hydratase, and the gamma subunit of thiocyanate hydrolase was homologous to the alpha subunit of nitrile hydratase [
]. |
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| Protein Domain |
| Name: |
Peptidase M11, gametolysin |
| Type: |
Domain |
| Description: |
Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation which is usually zinc, but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophillic role. Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site [
]. The HEXXH motif is relatively common, but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases [].This group of metallopeptidases belong to the MEROPS peptidase family M11 (gametolysin family, clan MA(M)). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA and the predicted active site residues for members of this family and thermolysin occur in the motif HEXXH [
].The type example is gametolysin from the unicellular biflagellated alga, Chlamydomonas reinhardtii Gametolysin is a zinc-containing metallo-protease, which is responsible for the degradation of the cell wall. Homologues of gametolysin have also been reported in the simple multicellular organism, Volvox [
,
]. |
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| Protein Domain |
| Name: |
Nuclear hormone receptor family 5 |
| Type: |
Family |
| Description: |
The nuclear hormone receptor subfamily 5 includes group A member 1 (NR5A1) or steroidogenic factor 1 (SF-1), group A member 2 (NR5A) or liver receptor homologue-1, and FTZ-F1 (group A member 3) and FTZ-F1 beta (group B member 1) from Drosophila [
,
]. SF-1 is a key regulator for steroid biosynthesis and essential for sexual differentiation and formation of the primary steroidogenic tissues [,
,
]. NR5A2 is involved in bile acid/cholesterol homeostasis and in the development of some human cancers [].Steroid or nuclear hormone receptors (NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members of the superfamily include the steroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands [
]. The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner [,
]. In addition to C-terminal ligand-binding domains, these nuclear receptors contain a highly-conserved, N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes, hormone resistance syndromes, etc. While several NRs act as ligand-inducible transcription factors, many do not yet have a defined ligand and are accordingly termed 'orphan' receptors. During the last decade, more than 300 NRs have been described, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members. |
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| Protein Domain |
| Name: |
RNA polymerase sigma-H type |
| Type: |
Family |
| Description: |
The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme [
]. RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.
With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors [
,
]. The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors [
].Members of this entry represent the RNA polymerase sigma-H factor required for sporulation in endospore-forming bacteria. These proteins are also called Sigma-30 and SigH. Related sequences exist in Listeria, but as Listeria does not form spores the role of these related sigma factors in that genus is in doubt. |
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| Protein Domain |
| Name: |
Phenylalanine-tRNA ligase, class II, N-terminal |
| Type: |
Domain |
| Description: |
Phenylalanine-tRNA ligase (also known as phenylalanyl-tRNA synthetase) from Thermus thermophilus has an alpha 2 beta 2 type quaternary structure and is one of the most complicated members of the ligase family. Identification of phenylalanine-tRNA ligase a member of class II aaRSs was based only on sequence alignment of the small alpha-subunit with other ligases [
]. This is the N-terminal domain of phenylalanine-tRNA ligase.The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c []. |
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| Protein Domain |
| Name: |
Peptidase S1A, alpha-lytic prodomain |
| Type: |
Domain |
| Description: |
Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes [
]. They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence []. Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases [].Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base [
]. The geometric orientations of the catalytic residues are similar between families, despite different protein folds []. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) [
,
].The alpha-lytic protease prodomain is associated with serine peptidases, specifically the alpha-lytic endopeptidases and streptogrisin A, B, C, D and E, which are bacterial enzymes and which belong to MEROPS peptidase subfamily S1A (
). The protease precursor in Gram-negative bacterial proteases may be a general property of extracellular bacterial proteases [
]. The proteases are encoded with a large (166 amino acid) N-terminal pro region that is required transiently both in vivoand
in vitrofor the correct folding of the protease domain [
,
]. The pro region also acts as a potent inhibitor of the mature enzyme []. |
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| Protein Domain |
| Name: |
Isochorismate synthase MenF |
| Type: |
Family |
| Description: |
Isochorismate synthase (
) catalyses the conversion of chorismate to isochorismate, the first step in the biosynthesis of both the respiratory chain component menaquinone (MK, vitamin K2) and phylloquinone (vitamin K1). In bacteria, isochorismate is a precursor of siderophores enterobactin (via the 2,3-dihydroxybenzoate (DHB) precursor) [
], amonabactins [] and salicylic acid []. Most aerobic bacteria secrete siderophores to facilitate iron acquisition []. Siderophores are iron-chelating agents which are low molecular weight compounds that specifically bind ferric iron and mediate iron uptake into the cell by recognition of specific membrane receptor proteins and transport systems. In plants, isochorismate synthase is required for defence against pathogens. Salicylic acid synthesised via the pathway using isochorismate synthase is responsible for both local and systemic acquired resistance in plants [].In Escherichia coli and Bacillus subtilis, two distinct isochorismate synthase isoenzymes, MenF [
] and EntC []/DhbC [], are known to be involved in MK and siderophore biosynthesis pathways, respectively []. MenF and EntC are differentially regulated and isochorismate synthesised by EntC is mainly channelled into enterobactin synthesis, whereas isochorismate synthesised by MenF is mainly channelled into menaquinone synthesis [].The catalytic/chorismate binding domain characteristic of members of this group is related to other chorismate binding enzymes [
]: component I of anthranilate synthase, para-aminobenzoate synthase, and aminodeoxychorismate synthase (please see ).
There is a significant heterogeneity in the length and sequence of the N-terminal region of members of this group. Partially on the basis of the N-terminal region, the group can be divided into subfamilies, with the enzymes involved in DHB (enterobactin precursor) biosynthesis (EntC/DhbC/VibC) forming a distinct subfamily, and the enzymes involved in MK biosynthesis (MenF) forming two groups (E. coli and B. subtilis types).This family represents MenF both from E. coli and B. subtilis. |
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•
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| Protein Domain |
| Name: |
Hydroxymethylglutaryl-CoA reductase, metazoan |
| Type: |
Family |
| Description: |
There are two distinct classes of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase enzymes: class I consists of eukaryotic and most archaeal enzymes (
), while class II consists of prokaryotic enzymes (
) [
,
].Class I HMG-CoA reductases catalyse the NADP-dependent synthesis of mevalonate from 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). In vertebrates, membrane-bound HMG-CoA reductase is the rate-limiting enzyme in the biosynthesis of cholesterol and other isoprenoids. In plants, mevalonate is the precursor of all isoprenoid compounds [
]. The reduction of HMG-CoA to mevalonate is regulated by feedback inhibition by sterols and non-sterol metabolites derived from mevalonate, including cholesterol. In archaea, HMG-CoA reductase is a cytoplasmic enzyme involved in the biosynthesis of the isoprenoids side chains of lipids []. Class I HMG-CoA reductases consist of an N-terminal membrane domain (lacking in archaeal enzymes), and a C-terminal catalytic region. The catalytic region can be subdivided into three domains: an N-domain (N-terminal), a large L-domain, and a small S-domain (inserted within the L-domain). The L-domain binds the substrate, while the S-domain binds NADP.Class II HMG-CoA reductases catalyse the reverse reaction of class I enzymes, namely the NAD-dependent synthesis of HMG-CoA from mevalonate and CoA [
]. Some bacteria, such as Pseudomonas mevalonii, can use mevalonate as the sole carbon source. Class II enzymes lack a membrane domain. Their catalytic region is structurally related to that of class I enzymes, but it consists of only two domains: a large L-domain and a small S-domain (inserted within the L-domain). As with class I enzymes, the L-domain binds substrate, but the S-domain binds NAD (instead of NADP in class I).This entry represents Metazoan class I HMG-CoA reductases, which are membrane-bound glycoproteins that remains in the endoplasmic reticulum after synthesis and glycosylation [
]. |
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•
|
| Protein Domain |
| Name: |
Cobalamin biosynthesis CobD/CbiB |
| Type: |
Family |
| Description: |
Cobalamin (vitamin B12) is a structurally complex cofactor, consisting of a modified tetrapyrrole with a centrally chelated cobalt. Cobalamin is usually found in one of two biologically active forms: methylcobalamin and adocobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes, whereas plants and fungi do not appear to use it. In bacteria and archaea, these include methionine synthase, ribonucleotide reductase, glutamate and methylmalonyl-CoA mutases, ethanolamine ammonia lyase, and diol dehydratase [
]. In mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase []. There are at least two distinct cobalamin biosynthetic pathways in bacteria [
]:Aerobic pathway that requires oxygen and in which cobalt is inserted late in the pathway [
]; found in Pseudomonas denitrificans and Rhodobacter capsulatus.Anaerobic pathway in which cobalt insertion is the first committed step towards cobalamin synthesis [
,
]; found in Salmonella typhimurium, Bacillus megaterium, and Propionibacterium freudenreichii subsp. shermanii. Either pathway can be divided into two parts: (1) corrin ring synthesis (differs in aerobic and anaerobic pathways) and (2) adenosylation of corrin ring, attachment of aminopropanol arm, and assembly of the nucleotide loop (common to both pathways) [
]. There are about 30 enzymes involved in either pathway, where those involved in the aerobic pathway are prefixed Cob and those of the anaerobic pathway Cbi. Several of these enzymes are pathway-specific: CbiD, CbiG, and CbiK are specific to the anaerobic route of S. typhimurium, whereas CobE, CobF, CobG, CobN, CobS, CobT, and CobW are unique to the aerobic pathway of P. denitrificans.This entry represents the CbiB protein, which is involved in cobalamin biosynthesis and porphyrin biosynthesis. It converts cobyric acid to cobinamide by the addition of aminopropanol on the F carboxylic group. It is part of the cob operon []. |
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•
|
| Protein Domain |
| Name: |
UROD/MetE-like superfamily |
| Type: |
Homologous_superfamily |
| Description: |
The crystal structure of human uroporphyrinogen decarboxylase (URO-D) shows it is comprised of a single domain containing a (beta/alpha)8-barrel with a deep active site cleft formed by loops at the C-terminal ends of the barrel strands [
]. The cobalamin-independent methionine synthase MetE consists of a duplication of a related domain. Each domain is a (beta/alpha)8-barrel with extended beta-alpha loops. The barrels are arranged face to face and the extended beta-alpha loops form the interface []. Uroporphyrinogen decarboxylase (URO-D), the fifth enzyme of the haem biosynthetic pathway, catalyses the sequential decarboxylation of the four acetyl side chains of uroporphyrinogen to yield coproporphyrinogen [
]. URO-D deficiency is responsible for the human genetic diseases familial porphyria cutanea tarda (fPCT) and hepatoerythropoietic porphyria (HEP). The sequence of URO-D has been well conserved throughout evolution. The best conserved region is located in the N-terminal section; it contains a perfectly conserved hexapeptide. There are two arginine residues in this hexapeptide which could be involved in the binding, via salt bridges, to the carboxyl groups of the propionate side chains of the substrate.Methionine synthases catalyse the the final step of methionine biosynthesis. Two apparently unrelated families of proteins catalyse this step: cobalamin-dependent methionine synthase, which catalyses the transfer of a methyl group from N5-methyltetrahydrofolate to L-homocysteine and requires cobalamin as a cofactor (MetH; 5-methyltetrahydrofolate:L-homocysteine S-methyltransferase;
) and cobalamin-independent methionine synthase, which catalyses the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine without using an intermediate methyl carrier (MetE; 5-methyltetrahydropteroyltri-L-glutamate:L-homocysteine S-methyltransferase;
). These enzymes display no detectable sequence homology between them, but both require zinc for activation and binding to L-homocysteine. Organisms that cannot obtain cobalamin (vitamin B12) encode only the cobalamin-independent enzyme. Escherichia coli and many other bacteria express both enzymes [
]. Mammals utilise only cobalamin-dependent methionine synthase, while plants and yeasts utilise only the cobalamin-independent enzyme. |
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| Protein Domain |
| Name: |
Nerve growth factor, beta subunit, mammalian |
| Type: |
Family |
| Description: |
During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells [
]. Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF), which is involved in the survival of some classes of embryonic neuron (e.g., peripheral sympathetic neurons) []. NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown []; it has also been found in several snake venoms [,
]. Proteins similar to NGF include brain-derived neurotrophic factor (BDNF) and neurotrophins 3 to 7, all of which demonstrate neuron survival and outgrowth activities. Although NGF was originally identified in snake venom, its most abundant and best studied source is the submaxillary gland of adult male mice [
]. Mouse NGF is a high molecular weight hexamer, composed of 2 subunits each of alpha, beta and gamma polypeptides. The beta subunit (NGF-beta) is responsible for the physiological activity of the complex [
]. NGF-beta induces its cell survival effects through activation of neurotrophic tyrosine kinase receptor type 1 (NTRK1; also called TrkA), and can induce cell death by binding to the low affinity nerve growth factor receptor, p75NTR [
]. The neurotophin has been shown to be involved in sympathetic axon growth and innervation of target fields []. Mammalian NGF-beta tend to be higher potency NTRK1 agonsits than their snake venom counterparts [
]. In humans, NGF-beta gene mutations can cause a loss of pain perception []. |
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•
|
| Protein Domain |
| Name: |
Restriction endonuclease type IV, Mrr |
| Type: |
Domain |
| Description: |
There are four classes of restriction endonucleases: types I, II,III and IV. All types of enzymes recognise specific short DNA sequences and carry out the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. They differ in their recognition sequence, subunit composition, cleavage position, and cofactor requirements [
,
], as summarised below:Type I enzymes (
) cleave at sites remote from recognition site; require both ATP and S-adenosyl-L-methionine to function; multifunctional protein with both restriction and methylase (
) activities.
Type II enzymes (
) cleave within or at short specific distances from recognition site; most require magnesium; single function (restriction) enzymes independent of methylase.
Type III enzymes (
) cleave at sites a short distance from recognition site; require ATP (but doesn't hydrolyse it); S-adenosyl-L-methionine stimulates reaction but is not required; exists as part of a complex with a modification methylase methylase (
).
Type IV enzymes target methylated DNA.This entry represents Mrr, a type IV restriction endonuclease involved in the acceptance of modified foreign DNA, restricting both adenine- and cytosine-methylated DNA. Plasmids carrying HincII, HpaI, and TaqI R and M genes are severely restricted in Escherichia coli strains that are Mrr+ []. Mrr appears to be the final effector of the bacterial SOS response, which is not only a vital reply to DNA damage but also constitutes an essential mechanism for the generation of genetic variability that in turn fuels adaptation and resistance development in bacterial populations []. Mrr possesses a cleavage domain that is similar to that found in type II restriction enzymes, however it has an unusual glutamine residue at the central position of the (D/E)-(D/E)XK hallmark of the active site []. |
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•
|
| Protein Domain |
| Name: |
Nitric oxide synthase, domain 3 superfamily |
| Type: |
Homologous_superfamily |
| Description: |
In eukaryotes, nitric oxide synthase (NOS) is a homodimeric enzyme with each monomer containing one C-terminal reductase domain and one N-terminal oxygenase domain. This entry represents a subdomain found in the oxygenase domain of NOS [
]. This domain can also be found in bacterial NOS that only has the oxygenase domain.Nitric oxide synthase (
) (NOS) enzymes produce nitric oxide (NO) by catalysing a five-electron oxidation of a guanidino nitrogen of L-arginine (L-Arg). Oxidation of L-Arg to L-citrulline occurs via two successive monooxygenation reactions producing N(omega)-hydroxy-L-arginine as an intermediate. 2 mol of O(2) and 1.5 mol of NADPH are consumed per mole of NO formed [
].Arginine-derived NO synthesis has been identified in mammals, fish, birds, invertebrates, plants, and bacteria [
]. Best studied are mammals, where three distinct genes encode NOS isozymes: neuronal (nNOS or NOS-1), cytokine-inducible (iNOS or NOS-2) and endothelial (eNOS or NOS-3) []. iNOS and nNOS are soluble and found predominantly in the cytosol, while eNOS is membrane associated. The enzymes exist as homodimers, each monomer consisting of two major domains: an N-terminal oxygenase domain, which belongs to the class of haem-thiolate proteins, and a C-terminal reductase domain, which is homologous to NADPH:P450 reductase (). The interdomain linker between the oxygenase and reductase domains contains a calmodulin (CaM)-binding sequence. NOSs are the only enzymes known to simultaneously require five bound cofactors animal NOS isozymes are catalytically self-sufficient. The electron flow in the NO synthase reaction is: NADPH -->FAD -->FMN -->haem -->O(2).
eNOS localisation to endothelial membranes is mediated by cotranslational N-terminal myristoylation and post-translational palmitoylation [
]. The subcellular localisation of nNOS in skeletal muscle is mediated by anchoring of nNOS to dystrophin. nNOS contains an additional N-terminal domain, the PDZ domain []. Some bacteria, like Bacillus halodurans, Bacillus subtilis or Deinococcus radiodurans, contain homologues of NOS oxygenase domain. |
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•
•
•
•
|
| Protein Domain |
| Name: |
Nitric oxide synthase, domain 1 superfamily |
| Type: |
Homologous_superfamily |
| Description: |
In eukaryotes, nitric oxide synthase (NOS) is a homodimeric enzyme with each monomer containing one C-terminal reductase domain and one N-terminal oxygenase domain. This entry represents a subdomain found in the oxygenase domain of NOS [
]. This domain can also be found in bacterial NOS that only has the oxygenase domain.Nitric oxide synthase (
) (NOS) enzymes produce nitric oxide (NO) by catalysing a five-electron oxidation of a guanidino nitrogen of L-arginine (L-Arg). Oxidation of L-Arg to L-citrulline occurs via two successive monooxygenation reactions producing N(omega)-hydroxy-L-arginine as an intermediate. 2 mol of O(2) and 1.5 mol of NADPH are consumed per mole of NO formed [
].Arginine-derived NO synthesis has been identified in mammals, fish, birds, invertebrates, plants, and bacteria [
]. Best studied are mammals, where three distinct genes encode NOS isozymes: neuronal (nNOS or NOS-1), cytokine-inducible (iNOS or NOS-2) and endothelial (eNOS or NOS-3) []. iNOS and nNOS are soluble and found predominantly in the cytosol, while eNOS is membrane associated. The enzymes exist as homodimers, each monomer consisting of two major domains: an N-terminal oxygenase domain, which belongs to the class of haem-thiolate proteins, and a C-terminal reductase domain, which is homologous to NADPH:P450 reductase (). The interdomain linker between the oxygenase and reductase domains contains a calmodulin (CaM)-binding sequence. NOSs are the only enzymes known to simultaneously require five bound cofactors animal NOS isozymes are catalytically self-sufficient. The electron flow in the NO synthase reaction is: NADPH -->FAD -->FMN -->haem -->O(2).
eNOS localisation to endothelial membranes is mediated by cotranslational N-terminal myristoylation and post-translational palmitoylation [
]. The subcellular localisation of nNOS in skeletal muscle is mediated by anchoring of nNOS to dystrophin. nNOS contains an additional N-terminal domain, the PDZ domain []. Some bacteria, like Bacillus halodurans, Bacillus subtilis or Deinococcus radiodurans, contain homologues of NOS oxygenase domain. |
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•
•
•
•
•
|
| Protein Domain |
| Name: |
Nitric oxide synthase, domain 2 superfamily |
| Type: |
Homologous_superfamily |
| Description: |
In eukaryotes, nitric oxide synthase (NOS) is a homodimeric enzyme with each monomer containing one C-terminal reductase domain and one N-terminal oxygenase domain. This entry represents a subdomain found in the oxygenase domain of NOS [
]. This domain can also be found in bacterial NOS that only has the oxygenase domain.Nitric oxide synthase (
) (NOS) enzymes produce nitric oxide (NO) by catalysing a five-electron oxidation of a guanidino nitrogen of L-arginine (L-Arg). Oxidation of L-Arg to L-citrulline occurs via two successive monooxygenation reactions producing N(omega)-hydroxy-L-arginine as an intermediate. 2 mol of O(2) and 1.5 mol of NADPH are consumed per mole of NO formed [
].Arginine-derived NO synthesis has been identified in mammals, fish, birds, invertebrates, plants, and bacteria [
]. Best studied are mammals, where three distinct genes encode NOS isozymes: neuronal (nNOS or NOS-1), cytokine-inducible (iNOS or NOS-2) and endothelial (eNOS or NOS-3) []. iNOS and nNOS are soluble and found predominantly in the cytosol, while eNOS is membrane associated. The enzymes exist as homodimers, each monomer consisting of two major domains: an N-terminal oxygenase domain, which belongs to the class of haem-thiolate proteins, and a C-terminal reductase domain, which is homologous to NADPH:P450 reductase (). The interdomain linker between the oxygenase and reductase domains contains a calmodulin (CaM)-binding sequence. NOSs are the only enzymes known to simultaneously require five bound cofactors animal NOS isozymes are catalytically self-sufficient. The electron flow in the NO synthase reaction is: NADPH -->FAD -->FMN -->haem -->O(2).
eNOS localisation to endothelial membranes is mediated by cotranslational N-terminal myristoylation and post-translational palmitoylation [
]. The subcellular localisation of nNOS in skeletal muscle is mediated by anchoring of nNOS to dystrophin. nNOS contains an additional N-terminal domain, the PDZ domain []. Some bacteria, like Bacillus halodurans, Bacillus subtilis or Deinococcus radiodurans, contain homologues of NOS oxygenase domain. |
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|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
986
|
| Description: |
psbQ-like protein 2, chloroplastic-like [Glycine max]; IPR008797 (Photosystem II PsbQ, oxygen evolving complex), IPR023222 (PsbQ-like domain); GO:0005509 (calcium ion binding), GO:0009523 (photosystem II), GO:0009654 (photosystem II oxygen evolving complex), GO:0015979 (photosynthesis), GO:0019898 (extrinsic component of membrane) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
1693
|
| Description: |
BEST Arabidopsis thaliana protein match is: Galact s in 8 species: Archae - 0; Bacteria - 0; Metazoa - 0; Fungi - 0; Plants - 30; Viruses - 0; Other Eukaryotes - 0 (source: NCBI BLink). |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
4422
|
| Description: |
ARF guanine-nucleotide exchange factor GNOM-like isoform X2 [Glycine max]; IPR000904 (Sec7 domain), IPR016024 (Armadillo-type fold), IPR023394 (Sec7 domain, alpha orthogonal bundle); GO:0005086 (ARF guanyl-nucleotide exchange factor activity), GO:0005488 (binding), GO:0032012 (regulation of ARF protein signal transduction) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
2927
|
| Description: |
subtilisin-like protease-like [Glycine max]; IPR015500 (Peptidase S8, subtilisin-related), IPR023827 (Peptidase S8, subtilisin, Asp-active site), IPR023828 (Peptidase S8, subtilisin, Ser-active site); GO:0004252 (serine-type endopeptidase activity), GO:0006508 (proteolysis), GO:0042802 (identical protein binding), GO:0043086 (negative regulation of catalytic activity) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
2104
|
| Description: |
CBL-interacting serine/threonine-protein kinase 8-like [Glycine max]; IPR011009 (Protein kinase-like domain), IPR015661 (Mitotic checkpoint serine/threonine protein kinase Bub1/Mitotic spindle checkpoint component Mad3); GO:0004672 (protein kinase activity), GO:0004674 (protein serine/threonine kinase activity), GO:0005524 (ATP binding), GO:0006468 (protein phosphorylation) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
1341
|
| Description: |
kinesin-related protein 11-like isoform X2 [Glycine max]; IPR001752 (Kinesin, motor domain), IPR027417 (P-loop containing nucleoside triphosphate hydrolase), IPR027640 (Kinesin-like protein); GO:0003777 (microtubule motor activity), GO:0005524 (ATP binding), GO:0005871 (kinesin complex), GO:0007018 (microtubule-based movement), GO:0008017 (microtubule binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
2317
|
| Description: |
coatomer subunit delta [Glycine max]; IPR011012 (Longin-like domain), IPR027059 (Coatomer delta subunit), IPR028565 (Mu homology domain); GO:0005515 (protein binding), GO:0006810 (transport), GO:0006886 (intracellular protein transport), GO:0016192 (vesicle-mediated transport), GO:0030126 (COPI vesicle coat), GO:0030131 (clathrin adaptor complex) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
2104
|
| Description: |
coatomer subunit delta [Glycine max]; IPR011012 (Longin-like domain), IPR027059 (Coatomer delta subunit), IPR028565 (Mu homology domain); GO:0005515 (protein binding), GO:0006810 (transport), GO:0006886 (intracellular protein transport), GO:0016192 (vesicle-mediated transport), GO:0030126 (COPI vesicle coat), GO:0030131 (clathrin adaptor complex) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
4596
|
| Description: |
uncharacterized protein LOC100818519 isoform X1 [Glycine max]; IPR003591 (Leucine-rich repeat, typical subtype), IPR016024 (Armadillo-type fold), IPR016035 (Acyl transferase/acyl hydrolase/lysophospholipase), IPR025875 (Leucine rich repeat 4); GO:0005488 (binding), GO:0005515 (protein binding), GO:0006629 (lipid metabolic process), GO:0008152 (metabolic process) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
10818
|
| Description: |
BEACH domain-containing protein lvsC-like isoform X5 [Glycine max]; IPR000409 (BEACH domain), IPR008985 (Concanavalin A-like lectin/glucanases superfamily), IPR013320 (Concanavalin A-like lectin/glucanase, subgroup), IPR015943 (WD40/YVTN repeat-like-containing domain), IPR016024 (Armadillo-type fold), IPR023362 (PH-BEACH domain); GO:0005488 (binding), GO:0005515 (protein binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
2041
|
| Description: |
kinesin-related protein 11-like isoform X2 [Glycine max]; IPR001752 (Kinesin, motor domain), IPR027417 (P-loop containing nucleoside triphosphate hydrolase), IPR027640 (Kinesin-like protein); GO:0003777 (microtubule motor activity), GO:0005524 (ATP binding), GO:0005871 (kinesin complex), GO:0007018 (microtubule-based movement), GO:0008017 (microtubule binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
3081
|
| Description: |
zinc finger CCCH domain-containing protein 44-like isoform X4 [Glycine max]; IPR003121 (SWIB/MDM2 domain), IPR003169 (GYF), IPR004343 (Plus-3), IPR013083 (Zinc finger, RING/FYVE/PHD-type); GO:0003677 (DNA binding), GO:0005515 (protein binding), GO:0005634 (nucleus), GO:0008270 (zinc ion binding), GO:0016570 (histone modification) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
3528
|
| Description: |
homeobox-leucine zipper protein ANTHOCYANINLESS 2-like isoform X2 [Glycine max]; IPR002913 (START domain), IPR009057 (Homeodomain-like), IPR023393 (START-like domain); GO:0003677 (DNA binding), GO:0003700 (sequence-specific DNA binding transcription factor activity), GO:0005634 (nucleus), GO:0008289 (lipid binding), GO:0043565 (sequence-specific DNA binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
3449
|
| Description: |
homeobox-leucine zipper protein ANTHOCYANINLESS 2-like isoform X2 [Glycine max]; IPR002913 (START domain), IPR009057 (Homeodomain-like), IPR023393 (START-like domain); GO:0003677 (DNA binding), GO:0003700 (sequence-specific DNA binding transcription factor activity), GO:0005634 (nucleus), GO:0008289 (lipid binding), GO:0043565 (sequence-specific DNA binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
1163
|
| Description: |
lon protease 2; IPR020568 (Ribosomal protein S5 domain 2-type fold), IPR027065 (Lon protease), IPR027417 (P-loop containing nucleoside triphosphate hydrolase); GO:0004176 (ATP-dependent peptidase activity), GO:0004252 (serine-type endopeptidase activity), GO:0005524 (ATP binding), GO:0006508 (proteolysis), GO:0030163 (protein catabolic process) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
2310
|
| Description: |
homeobox-leucine zipper protein ANTHOCYANINLESS 2-like isoform X2 [Glycine max]; IPR002913 (START domain), IPR009057 (Homeodomain-like), IPR023393 (START-like domain); GO:0003677 (DNA binding), GO:0003700 (sequence-specific DNA binding transcription factor activity), GO:0005634 (nucleus), GO:0008289 (lipid binding), GO:0043565 (sequence-specific DNA binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
2759
|
| Description: |
kinesin-related protein 11-like isoform X2 [Glycine max]; IPR001752 (Kinesin, motor domain), IPR027417 (P-loop containing nucleoside triphosphate hydrolase), IPR027640 (Kinesin-like protein); GO:0003777 (microtubule motor activity), GO:0005524 (ATP binding), GO:0005871 (kinesin complex), GO:0007018 (microtubule-based movement), GO:0008017 (microtubule binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
2839
|
| Description: |
kinesin-related protein 11-like isoform X1 [Glycine max]; IPR001752 (Kinesin, motor domain), IPR027417 (P-loop containing nucleoside triphosphate hydrolase), IPR027640 (Kinesin-like protein); GO:0003777 (microtubule motor activity), GO:0005524 (ATP binding), GO:0005871 (kinesin complex), GO:0007018 (microtubule-based movement), GO:0008017 (microtubule binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
4627
|
| Description: |
kinesin-related protein 11-like isoform X2 [Glycine max]; IPR001752 (Kinesin, motor domain), IPR027417 (P-loop containing nucleoside triphosphate hydrolase), IPR027640 (Kinesin-like protein); GO:0003777 (microtubule motor activity), GO:0005524 (ATP binding), GO:0005871 (kinesin complex), GO:0007018 (microtubule-based movement), GO:0008017 (microtubule binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
2253
|
| Description: |
homeobox-leucine zipper protein ANTHOCYANINLESS 2-like isoform X2 [Glycine max]; IPR002913 (START domain), IPR009057 (Homeodomain-like), IPR023393 (START-like domain); GO:0003677 (DNA binding), GO:0003700 (sequence-specific DNA binding transcription factor activity), GO:0005634 (nucleus), GO:0008289 (lipid binding), GO:0043565 (sequence-specific DNA binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
4578
|
| Description: |
kinesin-related protein 11-like isoform X2 [Glycine max]; IPR001752 (Kinesin, motor domain), IPR027417 (P-loop containing nucleoside triphosphate hydrolase), IPR027640 (Kinesin-like protein); GO:0003777 (microtubule motor activity), GO:0005524 (ATP binding), GO:0005871 (kinesin complex), GO:0007018 (microtubule-based movement), GO:0008017 (microtubule binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
3024
|
| Description: |
uncharacterized protein LOC100808415 isoform X4 [Glycine max]; IPR000157 (Toll/interleukin-1 receptor homology (TIR) domain), IPR002182 (NB-ARC), IPR027417 (P-loop containing nucleoside triphosphate hydrolase); GO:0000166 (nucleotide binding), GO:0005515 (protein binding), GO:0007165 (signal transduction), GO:0017111 (nucleoside-triphosphatase activity), GO:0043531 (ADP binding) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
570
|
| Description: |
psbQ-like protein 1, chloroplastic-like [Glycine max]; IPR008797 (Photosystem II PsbQ, oxygen evolving complex), IPR023222 (PsbQ-like domain); GO:0005509 (calcium ion binding), GO:0009523 (photosystem II), GO:0009654 (photosystem II oxygen evolving complex), GO:0015979 (photosynthesis), GO:0019898 (extrinsic component of membrane) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
3318
|
| Description: |
subtilisin-like protease-like [Glycine max]; IPR015500 (Peptidase S8, subtilisin-related), IPR023827 (Peptidase S8, subtilisin, Asp-active site), IPR023828 (Peptidase S8, subtilisin, Ser-active site); GO:0004252 (serine-type endopeptidase activity), GO:0006508 (proteolysis), GO:0042802 (identical protein binding), GO:0043086 (negative regulation of catalytic activity) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm3 |
| Annotation: |
ann1 |
| Length: |
443
|
| Description: |
clathrin heavy chain 2-like [Glycine max]; IPR016025 (Clathrin, heavy chain, linker/propeller domain); GO:0005198 (structural molecule activity), GO:0006886 (intracellular protein transport), GO:0016192 (vesicle-mediated transport), GO:0030130 (clathrin coat of trans-Golgi network vesicle), GO:0030132 (clathrin coat of coated pit) |
| Organism: |
Cicer arietinum |
| Strain: |
CDCFrontier |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
2553
|
| Description: |
uncharacterized protein LOC100808415 isoform X4 [Glycine max]; IPR000157 (Toll/interleukin-1 receptor homology (TIR) domain), IPR002182 (NB-ARC), IPR027417 (P-loop containing nucleoside triphosphate hydrolase); GO:0000166 (nucleotide binding), GO:0005515 (protein binding), GO:0007165 (signal transduction), GO:0017111 (nucleoside-triphosphatase activity), GO:0043531 (ADP binding) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
869
|
| Description: |
BEST Arabidopsis thaliana protein match is: Galact s in 8 species: Archae - 0; Bacteria - 0; Metazoa - 0; Fungi - 0; Plants - 30; Viruses - 0; Other Eukaryotes - 0 (source: NCBI BLink). |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
3456
|
| Description: |
homeobox-leucine zipper protein ANTHOCYANINLESS 2-like isoform X2 [Glycine max]; IPR002913 (START domain), IPR009057 (Homeodomain-like), IPR023393 (START-like domain); GO:0003677 (DNA binding), GO:0003700 (sequence-specific DNA binding transcription factor activity), GO:0005634 (nucleus), GO:0008289 (lipid binding), GO:0043565 (sequence-specific DNA binding) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
2799
|
| Description: |
zinc finger CCCH domain-containing protein 44-like isoform X1 [Glycine max]; IPR003121 (SWIB/MDM2 domain), IPR003169 (GYF), IPR004343 (Plus-3), IPR013083 (Zinc finger, RING/FYVE/PHD-type); GO:0003677 (DNA binding), GO:0005515 (protein binding), GO:0005634 (nucleus), GO:0008270 (zinc ion binding), GO:0016570 (histone modification) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
2105
|
| Description: |
coatomer subunit delta [Glycine max]; IPR011012 (Longin-like domain), IPR027059 (Coatomer delta subunit), IPR028565 (Mu homology domain); GO:0005515 (protein binding), GO:0006810 (transport), GO:0006886 (intracellular protein transport), GO:0016192 (vesicle-mediated transport), GO:0030126 (COPI vesicle coat), GO:0030131 (clathrin adaptor complex) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
2659
|
| Description: |
kinesin-related protein 11-like isoform X2 [Glycine max]; IPR001752 (Kinesin, motor domain), IPR027417 (P-loop containing nucleoside triphosphate hydrolase), IPR027640 (Kinesin-like protein); GO:0003777 (microtubule motor activity), GO:0005524 (ATP binding), GO:0005871 (kinesin complex), GO:0007018 (microtubule-based movement), GO:0008017 (microtubule binding) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
885
|
| Description: |
psbQ-like protein 1, chloroplastic-like [Glycine max]; IPR008797 (Photosystem II PsbQ, oxygen evolving complex), IPR023222 (PsbQ-like domain); GO:0005509 (calcium ion binding), GO:0009523 (photosystem II), GO:0009654 (photosystem II oxygen evolving complex), GO:0015979 (photosynthesis), GO:0019898 (extrinsic component of membrane) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
1371
|
| Description: |
chromodomain-helicase-DNA-binding protein 1-like isoform X2 [Glycine max]; IPR001650 (Helicase, C-terminal), IPR006917 (SOUL haem-binding protein), IPR011256 (Regulatory factor, effector binding domain), IPR027417 (P-loop containing nucleoside triphosphate hydrolase); GO:0003676 (nucleic acid binding), GO:0004386 (helicase activity), GO:0005524 (ATP binding) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
2629
|
| Description: |
homeobox-leucine zipper protein ANTHOCYANINLESS 2-like isoform X2 [Glycine max]; IPR002913 (START domain), IPR009057 (Homeodomain-like), IPR023393 (START-like domain); GO:0003677 (DNA binding), GO:0003700 (sequence-specific DNA binding transcription factor activity), GO:0005634 (nucleus), GO:0008289 (lipid binding), GO:0043565 (sequence-specific DNA binding) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
4623
|
| Description: |
kinesin-related protein 11-like isoform X2 [Glycine max]; IPR001752 (Kinesin, motor domain), IPR027417 (P-loop containing nucleoside triphosphate hydrolase), IPR027640 (Kinesin-like protein); GO:0003777 (microtubule motor activity), GO:0005524 (ATP binding), GO:0005871 (kinesin complex), GO:0007018 (microtubule-based movement), GO:0008017 (microtubule binding) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
2161
|
| Description: |
Protein kinase superfamily protein; IPR008985 (Concanavalin A-like lectin/glucanases superfamily), IPR011009 (Protein kinase-like domain), IPR013320 (Concanavalin A-like lectin/glucanase, subgroup); GO:0004672 (protein kinase activity), GO:0004674 (protein serine/threonine kinase activity), GO:0005524 (ATP binding), GO:0006468 (protein phosphorylation), GO:0030246 (carbohydrate binding) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
4923
|
| Description: |
DNA repair protein REV1-like isoform X2 [Glycine max]; IPR012112 (DNA repair protein, Rev1), IPR022880 (DNA polymerase IV); GO:0000287 (magnesium ion binding), GO:0003684 (damaged DNA binding), GO:0003887 (DNA-directed DNA polymerase activity), GO:0006281 (DNA repair), GO:0016779 (nucleotidyltransferase activity) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
2628
|
| Description: |
uncharacterized protein LOC100818519 isoform X1 [Glycine max]; IPR003591 (Leucine-rich repeat, typical subtype), IPR016024 (Armadillo-type fold), IPR016035 (Acyl transferase/acyl hydrolase/lysophospholipase), IPR025875 (Leucine rich repeat 4); GO:0005488 (binding), GO:0005515 (protein binding), GO:0006629 (lipid metabolic process), GO:0008152 (metabolic process) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
4675
|
| Description: |
kinesin-related protein 11-like isoform X2 [Glycine max]; IPR001752 (Kinesin, motor domain), IPR027417 (P-loop containing nucleoside triphosphate hydrolase), IPR027640 (Kinesin-like protein); GO:0003777 (microtubule motor activity), GO:0005524 (ATP binding), GO:0005871 (kinesin complex), GO:0007018 (microtubule-based movement), GO:0008017 (microtubule binding) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
807
|
| Description: |
eukaryotic translation initiation factor isoform 4G-1-like isoform 1 [Glycine max]; IPR001684 (Ribosomal protein L27), IPR003891 (Initiation factor eIF-4 gamma, MA3), IPR016024 (Armadillo-type fold); GO:0003735 (structural constituent of ribosome), GO:0005488 (binding), GO:0005622 (intracellular), GO:0005840 (ribosome), GO:0006412 (translation) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
3324
|
| Description: |
subtilisin-like protease-like [Glycine max]; IPR015500 (Peptidase S8, subtilisin-related), IPR023827 (Peptidase S8, subtilisin, Asp-active site), IPR023828 (Peptidase S8, subtilisin, Ser-active site); GO:0004252 (serine-type endopeptidase activity), GO:0006508 (proteolysis), GO:0042802 (identical protein binding), GO:0043086 (negative regulation of catalytic activity) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
4148
|
| Description: |
kinesin-related protein 11-like isoform X2 [Glycine max]; IPR001752 (Kinesin, motor domain), IPR027417 (P-loop containing nucleoside triphosphate hydrolase), IPR027640 (Kinesin-like protein); GO:0003777 (microtubule motor activity), GO:0005524 (ATP binding), GO:0005871 (kinesin complex), GO:0007018 (microtubule-based movement), GO:0008017 (microtubule binding) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
3021
|
| Description: |
uncharacterized protein LOC100808415 isoform X4 [Glycine max]; IPR000157 (Toll/interleukin-1 receptor homology (TIR) domain), IPR002182 (NB-ARC), IPR027417 (P-loop containing nucleoside triphosphate hydrolase); GO:0000166 (nucleotide binding), GO:0005515 (protein binding), GO:0007165 (signal transduction), GO:0017111 (nucleoside-triphosphatase activity), GO:0043531 (ADP binding) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
2890
|
| Description: |
kinesin-related protein 11-like isoform X2 [Glycine max]; IPR001752 (Kinesin, motor domain), IPR027417 (P-loop containing nucleoside triphosphate hydrolase), IPR027640 (Kinesin-like protein); GO:0003777 (microtubule motor activity), GO:0005524 (ATP binding), GO:0005871 (kinesin complex), GO:0007018 (microtubule-based movement), GO:0008017 (microtubule binding) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
| mRNA |
| Assembly: |
gnm1 |
| Annotation: |
ann1 |
| Length: |
2264
|
| Description: |
homeobox-leucine zipper protein ANTHOCYANINLESS 2-like isoform X2 [Glycine max]; IPR002913 (START domain), IPR009057 (Homeodomain-like), IPR023393 (START-like domain); GO:0003677 (DNA binding), GO:0003700 (sequence-specific DNA binding transcription factor activity), GO:0005634 (nucleus), GO:0008289 (lipid binding), GO:0043565 (sequence-specific DNA binding) |
| Organism: |
Cicer echinospermum |
| Strain: |
S2Drd065 |
|
•
•
•
•
•
|
