Phasins (or granule-associate proteins) are surface proteins found covering Polyhydroxyalkanoate (PHA) storage granules in bacteria. Polyhydroxyalkanoates are linear polyesters produced by bacterial fermentation of sugar or lipids for the purpose of storing carbon and energy, and are accumulated as intracellular granules by many bacteria under unfavorable conditions, enhancing their fitness and stress resistance [
]. The layer of phasins stabilises the granules and prevents coalescence of separated granules in the cytoplasm and nonspecific binding of other proteins to the hydrophobic surfaces of the granules. For example, in Ralstonia eutropha (strain ATCC 17699/H16/DSM 428/Stanier 337) (Cupriavidus necator (strain ATCC 17699 / H16 / DSM 428 / Stanier 337)), the major surface protein of polyhydroxybutyrate (PHB) granules is phasin PhaP1(Reu), which occurs along with three homologues (PhaP2, PhaP3, and PhaP4) that have the capacity to bind to PHB granules but are present at minor levels [,
]. These four phasins lack a highly conserved domain but share homologous hydrophobic regions. This entry represents a family of phasins that are part of the polyhydroxyalkanoate synthesis machinery [
]. Members of this family are related to .
D-lysine 5,6-aminomutase beta subunit KamE catalyses the 1,2-migration of the D-lysine epsilon amino group to the delta carbon with concomitant reverse migration of a hydrogen atom to produce 2,5-diaminohexanoic acid [
]. KamE contains two domains: the N-terminal dimerisation domain, which has the same fold as the Cu-binding domain of the Alzheimer's disease amyloid precursor protein, and the AdoCbl-binding Rossmann domain, which also provides the imine bond to pyridoxal 5'-phosphate. This entry represents the N-terminal dimerisation domain [
]. Proteins contain this domain also include L-beta-lysine 5,6-aminomutase beta subunit from Fusobacterium [].
This entry represents the probable protein kinase UbiB (also known as as AarF), which is required for ubiquinone biosynthesis [
,
,
]. It may function in regulating Q8 biosynthesis via its putative kinase activity [].
The members of this entry are similar to a region close to the C terminus of the HipA protein expressed by various bacterial species (for example
). This protein is known to be involved in high-frequency persistence to the lethal effects of inhibition of either DNA or peptidoglycan synthesis [
]. When expressed alone, it is toxic to bacterial cells [], but it is usually tightly associated with HipB [], and the HipA-HipB complex may be involved in autoregulation of the hip operon. The hip proteins may be involved in cell division control and may interact with cell division genes or their products []. The domain is also found in the serine/threonine-protein kinase CtkA from Helicobacter pyloriwhich is important in induction of host inflammation by inducing release of cytokines such as TNF-alpha and IL-8 by phosphorylation of NF-kappa-B [
].
AF2331-like protein is a 11kDa orphan protein from Archaeoglobus fulgidus. The structure consists of an alpha + beta fold formed by an unusual homodimer, where the two core β-sheets are interdigitated, containing strands alternating from both subunits. AF2331 contains multiple negatively charged surface clusters and is located on the same operon as the basic protein AF2330. It is suggested that AF2331 and AF2330 may form a charge-stabilised complex in vivo, though the role of the negatively charged surface clusters is not clear [
].
Ascorbate oxidase catalyzes the oxidation of ascorbic acid to dehydroascorbic acid. This multicopper oxidase (MCO) is found in cucurbitaceous plants such as pumpkin, cucumber, and melon. It can detect levels of ascorbic acid and eliminate it. The biological function of ascorbate oxidase is still not clear [
]; some studies suggest that it may play a crucial role in cell elongation and enlargement []. In pumpkin, its expression is increased during callus growth, fruit development and seedling elongation [].MCOs are capable of oxidizing a vast range of substrates, varying from aromatic compounds to inorganic compounds such as metals. Although the members of this family have diverse functions, majority of them have three cupredoxin domain repeats. The copper ions are bound in several sites: Type 1, Type 2, and/or Type 3. The ensemble of types 2 and 3 copper is called a trinuclear cluster. MCOs oxidize their substrate by accepting electrons at a mononuclear copper centre and transferring them to the active site trinuclear copper centre. The cupredoxin domain 1 of 3-domain MCOs contains part the trinuclear copper binding site, which is located at the interface of domains 1 and 3 [
].
The lipocalins are a diverse, interesting, yet poorly understood family of
proteins composed, in the main, of extracellular ligand-binding proteinsdisplaying high specificity for small hydrophobic molecules [
]. Functions of these proteins include transport of nutrients, control of cell regulation, pheromone transport, cryptic colouration, and the enzymatic synthesis of prostaglandins. The crystal structures of several lipocalins have been solved and show a novel 8-stranded anti-parallel β-barrel fold well conserved within the family. Sequence similarity within the family is at a much lower level and would seem to be restricted to conserved disulphides and 3 motifs, which form a juxtaposed cluster that may act as a common cell surface receptor site [
,
]. By contrast, at the more variable end of the fold are found an internal ligand binding site and a putative surface for the formation of macromolecular complexes []. The anti-parallel β-barrel fold is also exploited by the fatty acid-binding proteins, which function similarly by binding small hydrophobic molecules. Similarity at the sequence level, however, is less obvious, being confined to a single short N-terminal motif.A number of lipocalins act in invertebrate colouration and are represented in this entry. These include: bilin binding protein from the cabbage white butterfly (Pieris brassicae), the closely related protein insecticyanin from Manduca sexta (Tobacco hawkmoth) and the lobster protein crustacyanin. Like other members of the family, they bind small molecules, and gain their colourant properties from interaction with their ligands. Crustacyanin (meaning `shell blue') is the general name given to the
carotenoprotein complex found in the epicuticle, or calcified outer layer,of the lobster carapace. It acts as the dominant pigment of the lobster
shell, giving rise to its characteristic blue colour. In solution, crustacyanin exists as an equilibrium mixture between several distinct
forms, differing in their physical and spectral properties. The native, blue form (alpha-crustacyanin), which predominates in vivo, will, at low
ionic strength, form alpha'-crustacyanin; this in turn changes to purplebeta-crustacyanin on standing. The alpha to alpha' transition is favoured
by low ionic strength and is reversible, while conversion into beta-crustacyanin is irreversible. Native alpha-crustacyanin is an octamer of
heterodimers, totalling 16 separate polypeptide chains, each dimer binding two molecules of astaxanthin, beta-crustacyanin corresponding to the free
heterodimer.
Beta-carotene 15,15'-monooxygenase, Brp/Blh family
Type:
Family
Description:
This prokaryotic integral membrane protein family includes Brp (bacterio-opsin related protein) and Blh (Brp-like protein). Bacteriorhodopsin is a light-driven proton pump consisting of the membrane apoprotein bacterioopsin and a covalently bound retinal cofactor that appears to be derived of beta-carotene. Blh has been shown to cleave beta-carotene [
] to produce two all-trans retinal molecules. It has been suggested that Brp and Blh are similar proteins that catalyze or regulate the conversion of beta-carotene to retinal []. Mammalian enzymes with similar enzymatic function are not multiple membrane spanning proteins and are not homologous.
Uracil-DNA glycosylase inhibitors are DNA mimic proteins that prevent the DNA binding sites of UDGs (Uracil DNA glycosylase) from interacting with their DNA substrate. SSP0047 or SAUGI (for Staphylococcus aureus uracil-DNA glycosylase inhibitor) (
) acts as a uracil-DNA glycosylase inhibitor that breaks the uracil-removing activity of S. aureus uracil-DNA glycosylase (SAUDG,
) [
]. The SAUGI/SAUDG complex has been determined, and shows that SAUGI binds to the SAUDG DNA binding region via several strong interactions, by using a hydrophobic pocket to hold SAUDG's protruding residue (i.e. SAUDG Leu184, E. coli UDG Leu191 and B. subtilis UDG Phe191). By binding to SAUDG in this way, SAUGI thus prevents SAUDG from binding to its DNA substrate and performing DNA repair activity [].
PRTRC (ParB-Related, ThiF-Related Cassette) is a novel genetic system characterised by six or seven major proteins, included a ParB homologue and a ThiF homologue. It is often found on plasmids. PRTRC protein E averages about 150 amino acids in length, but the last third contains low-complexity sequence that complicates sequence comparisons. The model in this entry does not include the low-complexity region.
This entry represents a protein family which is homologous to the HlyD membrane fusion protein of type I secretion systems. The genes encoding these proteins within prokaryotic genomes are associated with genes encoding a novel class of microcin (small bacteriocin) which has a propeptide region related to nitrile hydratase. The bacteriocin has been designated as Nitrile Hydratase Propeptide Microcin, or NHPM. On this basis, therefore, proteins in this entry are designated as NHPM bacteriocin system secretion proteins. Some, but not all, NHPM-class putative microcins belong to the TOMM (thiazole/oxazole modified microcin) class as assessed by the presence of the scaffolding protein and/or cyclodehydratase in the same gene clusters.
This entry contains uncharacterised proteins with no known function, however they are predicted to be aspartic peptidases belonging to MEROPS clan AA [
] being related to family . These proteins resemble retropepsins, pepsin-like proteases of retroviruses such as HIV.
This family includes the small capsomere-interacting protein (SCP) from Gammaherpesviruses. By analogy with SCP from human herpesvirus 1, SCP forms a complex with the major capsid protein in the cytoplasm which is translocated to the nucleus. SCP decorates the outer surface of the capsid shell during capsid assembly, forming a layer between the capsid and the tegument.
Conserved hypothetical protein CHP02171, Fibrobacter succinogenes
Type:
Family
Description:
This entry represents a paralogous family of proteins found in the rumen bacterium Fibrobacter succinogenes. The proteins average over 900 amino acids in length and are of unknown function, though more than half are predicted lipoproteins.
Proteins in this entry are found in a proposed transfer region of a class of conjugative transposons found primarily in the Bacteroides lineage. PSI-BLAST reveals a distant relationship to proteins TrbF and VirB8 in proteobacterial conjugal transfer systems.
This family of proteins predominantly found in bacteria is functionally uncharacterised. Proteins in this family have two conserved sequence motifs, ExxQN and GAGLG.
These sequences represent a variant form of the serine biosynthesis enzyme phosphoserine aminotransferase, as found in a small number of distantly related species, including Caulobacter crescentus, Rhizobium loti (Mesorhizobium loti), and the archaeon Methanosarcina barkeri.
These sequences represent a putative variant form of the serine biosynthesis enzyme phosphoserine aminotransferase, as found in Mycobacterium tuberculosis and related high-GC Gram-positive bacteria.
This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000093) is described by MIBiG as an example of the following biosynthetic class, polyketide, in particular the meilingmycin biosynthetic gene cluster from Streptomyces nanchangensis [
,
]. This family appears to be predominantly found in bacteria.
This family of proteins found in bacteria and archaea is functionally uncharacterised. Proteins in this family are typically between 258 and 528 amino acids in length. There is a conserved GSC sequence motif.
This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001975) is described by MIBiG as an example of the following biosynthetic class, NRP (non-ribosomal peptide). It includes a member from the atratumycin biosynthetic gene cluster from Streptomyces atratus [
].
This family consists of RNA methyltransferases designated RlmC or RumB, formerly YbjF. Members act on 23S rRNA U747 in Escherichia coli and the equivalent position in other proteobacterial species [
].
This family consists of methyltransferases. The family member from Escherichia coli has been shown to have dual-specificity, catalysing the formation of 5-methyluridine at position 54 (m5U54) in all tRNAs, and that of position 341 (m5U341) in tmRNA (transfer-mRNA) [
,
,
]. This enzyme is inhibited by adenosylhomocysteine [].
This family consists of proteins believed to act as tRNA (uracil-5-)-methyltransferase (
). They catalyse the formation of 5-methyl-uridine at position 54 (m5U54) in tRNA and may have a role in tRNA stabilisation or maturation [
,
].Methyltransferases (EC [intenz:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule [,
,
]. All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM []. The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids [,
,
]. Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing [,
,
]. More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
tRNA (uracil(54)-C(5))-methyltransferase, metazoa type
Type:
Family
Description:
This entry represents a family of tRNA (uracil-5-)-methyltransferase homologues (
), mainly found in metazoa, including tRNA (uracil-5-)-methyltransferase homologue A (TRMT2A) and B (TRMT2B) from human. TRMT2A catalyses the formation of 5-methyl-uridine in tRNAs and some mRNAs [
,
,
]. TRMT2A/B mainly catalyse the methylation of uridine at position 54 (m5U54) in cytosolic tRNAs [,
]. This family also includes the plant homologue AtC3H24 (also known as TRNA METHYLTRANSFERASE 2B) [] and putative RNA methyltransferases R405/407 from Acanthamoeba polyphaga mimivirus.Methyltransferases (EC [intenz:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule [,
,
]. All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM []. The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids [,
,
]. Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing [,
,
]. More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria. There are two conserved sequence motifs: AMSY and DNS.
This family of proteins found in bacteria is functionally uncharacterised. Proteins in this family are typically between 298 and 349 amino acids in length. There is a conserved sequence pattern PxxxI/VxxGxxW.
This entry represents the ligand-binding domain found in ephrin type-A receptor 1 (EphA1). Alteration in EphA1 expression levels have been reported in colorectal and gastric cancers, as well as melanomas [
,
,
]. Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands [
,
]. Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling) [
].
The Eph receptors, which bind a group of cell-membrane-anchored ligands known
as ephrins, represent the largest subfamily of receptor tyrosine kinases(RTKs). The Eph receptors and their ephrin ligands control a
diverse array of cell-cell interactions in the nervous and vascular systems.On ephrin binding, the Eph kinase domain is activated, initiating 'forward'
signaling in the receptor-expressing cells. Simultaneously, signals are alsoinduced in the ligand-expressing cells a phenomenon referred to as 'reverse'
signalling. The extracellular Eph receptor region contains a conserved 180-amino-acid N-terminal ligand-binding domain (LBD) which is both necessary and
sufficient for bindings of the receptors to their ephrin ligands. An adjacentcysteine-rich region might be involved in receptor-receptor oligomerization
often observed on ligand binding, whereas the next two fibronectin type IIIrepeats have yet to be assigned a clear biological function.
The cytoplasmic Eph receptor region contains a kinase domain, a sterile alpha motif (SAM) domain, and a PDZ-binding motif. The ligand-binding domain (LBD) of Eph receptors is unique tothis family of RTKs ans shares no significant amino-acid-sequence homology
with other known proteins [,
,
].The Eph LBD domain forms a compact globular structure which folds into ajellyroll β-sandwich composed of 11 antiparallel β-strands. It has two antiparallel β-sheets, with the usual left-handed
twist, packed against each other to form a compact β-sandwich, and a short3(10) helix [
,
,
].
Ephrins and their receptors EphR play an important role in cell communication in normal physiology, as well as in disease pathogenesis [
,
]. Binding of the ephrin (Eph) ligand to EphR requires cell-cell contact, since both molecules are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling, depending on Eph kinase activity) and ephrin-expressing cells (reverse signaling) [,
,
]. Eph signaling controls cell morphology, adhesion, migration and invasion.Ephrins can be subdivided into two groups, A and B, depending on their respective receptors EphA or EphB. The nine human EphA receptors bind to five GPI-linked ephrin-A ligands [
]. Interactions are promiscuous within each class, and some Eph receptors can also bind to ephrins of the other class. All ephrin As contain a highly conserved receptor binding ectodomain described by this entry. Although ephrin As do not have a cytoplasmic tail (in contrast to ephrin Bs), they are still capable of downstream activation of Src family kinases and phosphoinositide-3-kinases, most likely involving co-receptors such as neurotrophin receptors [,
].
This entry contains proteins of unknown function, which include HutD from Pseudomonas fluorescens and Ves from Escherichia coli K12.HutD from P. fluorescens is a component of the histidine uptake and utilisation operon. HutD is operonic with the well characterised repressor protein HutC. Genetic analysis using transcriptional fusions (lacZ) and deletion mutants shows that hutD is necessary to maintain fitness in environments replete with histidine. HutD probably sets an upper bound on the level of hut operon transcription [
]. The mechanistic basis is unknown, but in silico molecular docking studies based on the crystal structure of HutD from Pseudomonas aeruginosa show that urocanate (the first breakdown product of histidine) docks with the active site of HutD.
Proteins of the Ves family have no known function. Ves is induced by various environmental stresses, including low temperature, osmotic shock and oxygen. Expression is induced more than 10 fold by reducing temperature from 37 to 25 degrees Celsius [
].
Ephrins and their receptors EphR play an important role in cell communication in normal physiology, as well as in disease pathogenesis [
,
]. Binding of the ephrin (Eph) ligand to EphR requires cell-cell contact, since both molecules are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling, depending on Eph kinase activity) and ephrin-expressing cells (reverse signaling) [,
,
]. Eph signaling controls cell morphology, adhesion, migration and invasion. Ephrins can be subdivided into two groups, A and B, depending on their respective receptors EphA or EphB. The nine human EphA receptors bind to five GPI-linked ephrin-A ligands and the five EphB receptors bind to three transmembrane ephrin-B ligands []. Interactions are promiscuous within each class, and some Eph receptors can also bind to ephrins of the other class.Ephrin Bs have several conserved tyrosine phosphorylation sites in their cytoplasmic PDZ-like domain, which are important for signal transduction [
]. All ephrin Bs contain a highly conserved receptor binding ectodomain described in this entry.
The ATP-Binding Cassette (ABC) superfamily forms one of the largest of all protein families with a diversity of physiological functions [
]. Several studies have shown that there is a correlation between the functional characterisation and the phylogenetic classification of the ABC cassette [,
]. More than 50 subfamilies have been described based on a phylogenetic and functional classification [,
,
].This family consists of several bacterial ABC transporter proteins which are homologous to the EcsB protein of Bacillus subtilis. EcsB is thought to encode a hydrophobic protein with six membrane-spanning helices in a pattern found in other hydrophobic components of ABC transporters [
].
Ascorbate oxidase catalyzes the oxidation of ascorbic acid to dehydroascorbic acid. This multicopper oxidase (MCO) is found in cucurbitaceous plants such as pumpkin, cucumber, and melon. It can detect levels of ascorbic acid and eliminate it. The biological function of ascorbate oxidase is still not clear [
]; some studies suggest that it may play a crucial role in cell elongation and enlargement []. In pumpkin, its expression is increased during callus growth, fruit development and seedling elongation [].MCOs couple oxidation of substrates with reduction of dioxygen to water. Although MCOs have diverse functions, majority of them have three cupredoxin domain repeats that include one mononuclear and one trinuclear copper centre. The copper ions are bound in several sites: Type 1, Type 2, and/or Type 3. The ensemble of types 2 and 3 copper is called a trinuclear cluster. MCOs oxidize their substrate by accepting electrons at a mononuclear copper centre and transferring them to the active site trinuclear copper centre [
]. The cupredoxin domain 2 of 3-domain MCOs has lost the ability to bind copper.
This protein family is found in bacteria, including Protein YciF from Escherichia coli. This protein is produced by bacteria in response to stress conditions. It adopts a dimeric configuration in which each monomer shows five α-helices. Its function is still unknown [
].
This family includes poorly characterised bacterial proteins, such as YciF from Escherichia coli. This protein is produced by bacteria in response to stress conditions. It adopts a dimeric configuration in which each monomer shows five α-helices. Its function is still unknown [
].
Integrating conjugative element protein PilL, PFGI-1
Type:
Domain
Description:
This entry describes the conserved N-terminal region of a variable length protein family associated with laterally transfered regions flanked by markers of conjugative plasmid integration and/or transposition. Most members of the family have the lipoprotein signal peptide motif. A member of the family from a pathogenicity island in Salmonella enterica subsp enterica serovar Dublin strain was designated PilL for nomenclature consistency with a neighbouring gene for the pilin structural protein PilS. However, the species distribution of this protein family tracks much better with markers of conjugal transfer than with markers of PilS-like pilin structure.
Proteins on this entry are usually encoded on the bacterial chromosome, in regions flanked by markers of conjugative transfer and/or transposition. In some cases, however, they are encoded on plasmids. Many are annotated as putative lipoproteins.
Members of this protein family are found sparsely, mostly in members of the genus Burkholderia. Members often occur as tandem homologous genes, such as BMA_0021 and BMA_0022 in Burkholderia mallei ATCC 23344, or else have a duplication. The genes regularly are encoded near a cyclodehydrogenase/docking protein fusion protein of TOMM (thiazole/oxazole-modified microcins) biosynthetic clusters, suggesting a role in bacteriocin biosynthesis. The role of the putative natural product is unknown, but function as a two-chain bacteriocin is suggested.
This entry describes a novel form of signal peptide that occurs as an N-terminal domain with a recognisable motif, reminiscent of the YSIRK and PEP-CTE forms of signal peptide. This domain tends to occur on long, low-complexity (usually serine-rich and heavily glycosylated) proteins of the Firmicutes, and (as with YSIRK) the majority of these proteins have the LPXTG cell wall-anchoring motif at the C terminus [
,
,
].
Integrating conjugative element protein, PFL4697-type
Type:
Family
Description:
Proteins in this entry are usually encoded on the bacterial main chromosome, in regions flanked by markers of conjugative transfer and/or transposition. Occasionally, however, they are encoded on plasmids such as the Pseudomonas putida TOL plasmid.
This entry represents an uncharacterised protein family that occurs only among the roughly 8 percent of prokaryotic species that carry homologues of the integral membrane protein exosortase (see
), a proposed protein-sorting system transpeptidase.
This entry represents Transposase for transposon Tn554 and related proteins mainly found in firmicutes and actinobacteria. This protein family is one of three encoded by transposon Tn554 and required for its transposition [
]. There is a conserved sequence GV/LSR/K and a highly conserved Tyrosine residue.
This protein family contains proteins with a median length of about 175, including a strongly conserved N-terminal region of about 55 amino acids, a conserved extreme C-terminal region of about 15 amino acids, and highly variable sequence in between the two.
This family of bacterial proteins is functionally uncharacterised. Proteins in this family are typically between 246 and 334 amino acids in length. Some members are thought to be hemagglutinin-related proteins.
Proteins in this entry form part of an accessory Sec system which is involved in the export of serine-rich glycoproteins important for virulence in a number of Gram-positive species, including Streptococcus gordonii and Staphylococcus aureus [
,
]. Asp2 directly interacts with Aps1 and Asp3 to form a complex and stabilizes it; this complex is essential for substrate export. Asp2 and Asp3 interact directly with GspB and may function in part as chaperones in the early phase of GspB transport []. Moreover, Asp2 acetylates the GlcNAc residues on GspB. Asp1/2/3 complex stimulates the ATPase activity of SecA2 and also affects the export and glycosylation of pneumococcal serine-rich repeat proteins (PrsPs) [
].
This domain is mainly found in bacterial proteins and is functionally uncharacterised. However, some proteins containing this domain are putative glycoside hydrolases and this domain has some overlaps with clan family members of CL0058. Proteins containing this domain are typically between 678 and 749 amino acids in length.
Conserved hypothetical protein CHP03806, HNE0200 family
Type:
Domain
Description:
This entry represents an uncharacterised protein which is associated with another uncharacterised protein containing β-helix repeats (
). These two proteins are usually encoded adjacently, either as separate genes or in a fusion. Sometimes two proteins in this entry occur with a single member of
. The function of these proteins is unknown.
This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000974) is described by MIBiG as an example of the following biosynthetic classes, NRP (non-ribosomal peptide) and polyketide. It includes a member from the crocacin biosynthetic gene cluster from Chondromyces crocatus [
].
This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000700) is described by MIBiG as an example of the following biosynthetic class, saccharide. It includes a member from the istamycin biosynthetic gene cluster from Streptomyces tenjimariensis [
].
This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001215) is described by MIBiG as an example of the following biosynthetic class, NRP (non-ribosomal peptide). It includes a member from the conglobatin biosynthetic gene cluster from Streptomyces conglobatus [
].
This family represents the plant homologues of C. elegans uncoordinated protein 93 (also called putative potassium channel regulatory protein unc-93), including UNC93-like protein 3 from Arabidopsis thaliana. It maintains K+ homeostasis through abscisic acid (ABA) signalling pathway, which positively regulates abiotic stress tolerance and plant growth [
].
This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001662) is described by MIBiG as an example of the following biosynthetic class, polyketide. It includes a member from the mediomycin A biosynthetic gene cluster from Kitasatospora mediocidica [
].
This family of bacterial proteins is functionally uncharacterised. Proteins in this family are typically between 39 and 59 amino acids in length. This family contains a highly conserved sequence HGKV/IKS/T.
This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001778) is described by MIBiG as an example of the following biosynthetic class, other (unspecified). It includes a member from the showdomycin biosynthetic gene cluster from Streptomyces showdoensis [
].
This is a family of transport proteins. Members of this family include a protein responsible for the secretion of the ferric chelator, enterobactin [
], and a protein involved in antibiotic resistance [].
This is a family of bacterial proteins that are likely to be part of the Na(+)-dependent bicarbonate transporter (sbt) family. Members carry 10TMS in a 5+5 duplicated structure. The loop between helices 5 and 6 in Synechocystis PCC6803 is likely to be the location for regulatory mechanisms governing the activation of the transporter [
].
MauL is one of the products from the methylamine utilization gene cluster in Methylobacterium extorquens AM1 [
]. Mutants generated by insertions in mauL were not able to grow on methylamine or any other primary amine as carbon sources. MauL belongs to the blue or type I copper protein family, which are involved in electron transfer reactions, with the Cu centre transitioning between the oxidized Cu(II) form and the reduced Cu(I) form [].
This entry represents the Spacer-1 domain found in ADAM-TS and ADAM-TS-like proteins.Proteolysis of the extracellular matrix plays a critical role in establishing tissue architecture during development and in tissue degradation in diseases such as cancer, arthritis, Alzheimer's disease and a variety of inflammatory conditions [
,
]. The proteolytic enzymes responsible for this process are members of diverse protease families, including the secreted zinc metalloproteases (MPs) []. ADAM-TS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) is closely related to the ADAM family (A Disintegrin and Metalloproteinase) and is a subfamily of the MP family, consists of at least 20 members sharing a high degree of sequence similarity and conserved domain organisation [
,
]. The defining domains of the ADAM-TS family are (from N- to C-termini) a pre-pro metalloprotease domain of the reprolysin type, a snake venom disintegrin-like domain, a thrombospondin type-I (TS) module, a cysteine-rich region, and a cysteine-free (spacer) domain []. Domain organisation following the spacer domain C terminus shows some variability in certain ADAM-TS members, principally in the number of additional TS domains. These enzymes have a wide-spectrum role in vascular biology and cardiovascular pathophysiology [].Members of the ADAM-TS family have been implicated in a range of diseases [
,
,
]. For instance, members of this family have been found to participate directly in processes in the central nervous system (CNS) such as the regulation of brain plasticity []. ADAM-TS1 is reported to be involved in inflammation and cancer cachexia [], whilst recessively inherited ADAM-TS2 mutations cause Ehlers-Danlos syndrome type VIIC, a disorder characterised clinically by severe skin fragility []. ADAM-TS4 is an aggrecanase involved in arthritic destruction of cartilage []. ADAM-TS-like proteins lack a metalloprotease domain. They resides in the ECM and have regulatory roles []. Examples of ADAM-TS-like proteins are papilin [] and punctin [].
This entry represents the ligand-binding domain found in ephrin type-B receptor 3 (EphB3). EphB3 plays a role in cell positioning in the gastrointestinal tract by being preferentially expressed in Paneth cells [
]. It also has been implicated in early colorectal cancer and early stage squamous cell lung cancer []. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands [
].Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling) [
].
Sulfocyanin is a blue copper protein with a putative membrane anchoring hydrophobic motif at the N terminus. It may substitute for cytochrome C in electron transfer reactions in archaea [
].
This entry represents the ligand-binding domain found in ephrin type-B receptor 2 (EphB2). EphB2 plays a role in cell positioning in the gastrointestinal tract by being expressed in proliferating progenitor cells [
]. It also has been implicated in colorectal cancer [,
]. A loss of EphB2, as well as EphA4, also precedes memory decline in a murine model of Alzheimers disease [].Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands [
].Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling) [
].
Ribosomal protein L13 is one of the proteins from the large ribosomal subunit [
]. In Escherichia coli, L13 is known to be one of the early assembly proteins of the 50S ribosomal subunit.Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].The structure of the L13 domain is composed of three layers (alpha/beta/alpha) with parallel β-sheet of four strands.
This entry represents the carboxypeptidase domain (CPD) found in carboxypeptidase Z. Carboxypeptidase Z (CPZ; MEROPS identifier M14.012) belongs to subfamily M14B (N/E subfamily) of the M14 family of metallocarboxypeptidases (MCPs) [
]. CPZ is a secreted Zn-dependent enzyme whose biological function is largely unknown. Unlike other members of the N/E subfamily, CPZ has a bipartite structure, which consists of an N-terminal cysteine-rich domain (CRD) whose sequence is similar to Wnt-binding proteins, and a C-terminal CP catalytic domain that removes C-terminal Arg residues from substrates. CPZ is enriched in the extracellular matrix and is widely distributed during early embryogenesis [,
]. That the CRD of CPZ can bind to Wnt4 suggests that CPZ plays a role in Wnt signaling [,
].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 [,
].
The long cytoplasmic tubular structure of the T6SS system is wrapped by a sheath structure composed of two proteins, TssB and TssC. Contraction of the sheath causes the internal tube of the T6SS with associated effectors to be propelled out of the effector cell and across the membranes of bacterial or eukaryotic target cells [
,
,
].TssB and TssC assemble into tubular structures with cogwheel patterns resembling the bacteriophage contractile sheath [
]. Several structures of T6SS sheath assemblies have been solved displaying a helical assembly [,
,
]. Interactions between TssB and TssC occur between the N-terminal region of TssC and the conserved a-helix of TssB []. The two proteins of the F. novicida T6SS outer sheath, IglA (TssB) and IglB (TssC), are interdigitated into a single fold similar to that of the phage sheath. The F. novicida T6SS outer sheath has a highly interlaced two-dimensional array architecture with augmented beta sheets that is essential to secretory function [].Three distinct T6SS subtypes exist, T6SSi, in which most proteobacterial T6SSs are found, including V. cholerae and P. aeruginosa; T6SSii for the Francisella T6SS; and T6SSiii for Bacteroidetes systems [
].TssB/TssC are also known as IglA/IglB and VipA/VipB.The type VI secretion system (T6SS) is a supra-molecular bacterial complex that resembles phage tails. It is a toxin delivery systems which fires toxins into target cells upon contraction of its TssBC sheath [
]. Thirteen essential core proteins are conserved in all T6SSs: the membrane associated complex TssJ-TssL-TssM, the baseplate proteins TssE, TssF, TssG, and TssK, the bacteriophage-related puncturing complex composed of the tube (Hcp), the tip/puncturing device VgrG, and the contractile sheath structure (TssB and TssC). Finally, the starfish-shaped dodecameric protein, TssA, limits contractile sheath polymerization at its distal part when TagA captures TssA [].
This superfamily represents the host-nuclease inhibitor protein Gam. Structurally, it consists of 4 alpha helices, 2 long and 2 short.
Within bacteriophage lambda protein Gam, one of the long helices (H4) acts as a dimerisation interface to form an antiparallel helix. The two short helices (H2 and H3) from each dimer form a 'cross-brace', while the other long helix (H1) protrudes out of the protein []. Within bacteriophage lambda, Gam is involved in inhibiting host nucleases.
This entry represents a family of Gram-negative bacterial proteins involved in the Dot/Icm type IVb transport system, including IcmS from Legionella pneumophila. Members are small acidic cytoplasmic proteins required for Dot/Icm-dependent activities [
]. IcmS is part of a subcomplex which recruits effector proteins and delivers them to the core transmembrane subcomplex [,
].
SepZ is a component of the type III secretion system use in bacteria. SepZ is a gene within the enterocyte effacement locus. SepZ mutants exhibit reduced invasion efficiency and lack of tyrosine phosphorylation of Hp90 [
].
This family of proteins is found in bacteria and viruses. Proteins in this family are approximately 130 amino acids in length. There are two conserved sequence motifs: LPS and LKR. Overproduction of ribosome recycling factor (RRF) reduces tna operon expression and increases the rate of cleavage of TnaC-tRNA(2)(Pro), relieving the growth inhibition associated with plasmid-mediated tnaC overexpression.
Suppressors of cytokine signaling (SOCS) proteins play important roles in regulating a variety of signal transduction pathways that are involved in immunity, growth and development of organisms. They share a similar domain organisation, with a central SH2 domain and a conserved C-terminal SOCS box. In contrast, the N-terminal domains vary in length and amino acid sequence. In the case of SOCS4-7, the N-terminal domain accounts for a large proportion of the protein [
].This entry represents a conserved region in the N-terminal domains of SOCS4 and 5. This domain is approximately 60 amino acids in length. It is found in association with
,
.
PHD finger protein 20 (PHF20) is a Methyllysine-binding protein, component of the MOF histone acetyltransferase protein complex. It consists of tandem Tudor domains at the N-terminal, an AT hook, a C2H2-type zinc finger, and a plant homeodomain (PHD) finger [
,
,
]. PHF20L1 binds to monomethylated lysine 142 on DNA (cytosine-5) methyltransferase 1 (DNMT1). It has been shown to antagonize DNMT1 proteasomal degradation [].This is the AT-hook domain found in PHD finger protein 20 (PHF20) and PHD finger protein 20-like (PHF20L) [
,
,
].
This family of proteins found mainly in Bacteroidetes is functionally uncharacterised. A conserved glycine residue and the conserved sequences GTF and GxF can be found at the C terminus.
This family consists of several US9 and related proteins from the Alphaherpesviruses. The function of the US9 protein is unknown although in Bovine herpesvirus 5 Us9 is essential for the anterograde spread of the virus from the olfactory mucosa to the bulb [
]. Together with the gE/gI heterodimer, US9 is involved in the sorting and transport of viral structural components toward axon tips [].
This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000700) is described by MIBiG as an example of the following biosynthetic class, saccharide. It includes a member from the istamycin biosynthetic gene cluster from Streptomyces tenjimariensis [
].
This domain is found in plants and fungi. It represents the C-terminal extracellular domain of the putative phosphate transporter, PHM7 [
]. The three N-terminal TMS are found in family RSN1_TM, ; the cytoplssmic domain is
, and the remaining 7TM region is in
.
This domain is mainly found in bacterial proteins which are functionally uncharacterised. There is a conserved Tryptophan residue at the N-terminal and a highly conserved SDLN sequence.
This domain is found in uncharacterised plant proteins, and is typically between 48 and 61 amino acids in length. There is a conserved LRF sequence motif.
Asp3 is part of an accessory SecA2/SecY2 system, which is involved in the export of serine-rich glycoproteins important for virulence in a number of Gram-positive species, including Streptococcus gordonii and Staphylococcus aureus [
]. SecA2/SecY2 system specifically required to export SraP, a serine-rich repeat cell wall protein encoded upstream in the same operon []. In Streptococcus gordonii, it may also function in part as chaperones in the early phase of GspB (a serine-rich glycoprotein adhesin) transport [].
This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000703) is described by MIBiG as an example of the following biosynthetic class, saccharide. It includes a member from the kanamycin biosynthetic gene cluster from Streptomyces kanamyceticus [
].
Proteins in this entry are encoded by a gene that is found in flagellar operons of Bacillus-related organisms. The function is unknown. A tentative assignment as a regulator has been made in some sources.
