This entry represents a conserved domain found in the Rab3 GTPase-activating protein catalytic subunit (Rab3GAP1).
Small G proteins of the Rab family are regulators of intracellular vesicle traffic. Their rate of GTP hydrolysis is enhanced by specific GTPase-activating proteins (GAPs) that switch G proteins to their inactive form [
]. Rab3GAP1 (catalytic subunit) has been shown to form a heterodimeric complex with Rab3GAP2 (the regulatory subunit), and this complex acts as a guanosine nucleotide exchange factor for Rab3 subfamily (RAB3A, RAB3B, RAB3C and RAB3D). Rab3GAP complex may participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters [,
]. It also activates Rab18 and promotes autolysosome maturation through the Vps34 Complex I [].Mutations in the Rab3GAP1/2 gene cause Warburg micro syndrome (WMS), a hereditary autosomal neuromuscular disorder [
].
This entry represents a group of plant auxin-responsive proteins, known as small auxin-up RNA (SAUR) [
]. The first SAUR gene was originally identified in soybean hypocotyls []. SAUR genes are mainly expressed in growing hypocotyls or other elongating tissues, implying that they play a role in the regulation of cell elongation []. SAUR proteins may provide a mechanistic link between auxin and plasma membrane H+-ATPases (PM H+-ATPases) in Arabidopsis thaliana [].
Glutamine amidotransferase (GATase) enzymes catalyse the removal of the ammonia group from glutamine and then transfer this group to a substrate to form a new carbon-nitrogen group [
]. The GATase domain exists either as a separate polypeptidic subunit or as part of a larger polypeptide fused in different ways to a synthase domain. Two classes of GATase domains have been identified [
,
]: class-I (also known as trpG-type or triad) and class-II (also known as purF-type or Ntn). Class-I (or type 1) GATase domains have been found in the following enzymes:The second component of anthranilate synthase (AS) [
]. AS catalyzes the biosynthesis of anthranilate from chorismate and glutamine. AS is generally a dimeric enzyme: the first component can synthesize anthranilate using ammonia rather than glutamine, whereas component II provides the GATase activity []. In some bacteria and in fungi the GATase component of AS is part of a multifunctional protein that also catalyzes other steps of the biosynthesis of tryptophan.The second component of 4-amino-4-deoxychorismate (ADC) synthase, a dimeric prokaryotic enzyme that functions in the pathway that catalyzes the biosynthesis of para-aminobenzoate (PABA) from chorismate and glutamine. The second component (gene pabA) provides the GATase activity [
].CTP synthase. CTP synthase catalyzes the final reaction in the biosynthesis of pyrimidine, the ATP-dependent formation of CTP from UTP and glutamine. CTP synthase is a single chain enzyme that contains two distinct domains; the GATase domain is in the C-terminal section [
].GMP synthase (glutamine-hydrolyzing). GMP synthase catalyzes the ATP-dependent formation of GMP from xanthosine 5'-phosphate and glutamine. GMP synthase is a single chain enzyme that contains two distinct domains; the GATase domain is in the N-terminal section [
,
].Glutamine-dependent carbamoyl-phosphate synthase (GD-CPSase); an enzyme involved in both arginine and pyrimidine biosynthesis and which catalyzes the ATP-dependent formation of carbamoyl phosphate from glutamine and carbon dioxide. In bacteria GD-CPSase is composed of two subunits: the large chain (gene carB) provides the CPSase activity, while the small chain (gene carA) provides the GATase activity. In yeast the enzyme involved in arginine biosynthesis is also composed of two subunits: CPA1 (GATase), and CPA2 (CPSase). In most eukaryotes, the first three steps of pyrimidine biosynthesis are catalyzed by a large multifunctional enzyme (called URA2 in yeast, rudimentary in Drosophila, and CAD in mammals). The GATase domain is located at the N-terminal extremity of this polyprotein [
].Phosphoribosylformylglycinamidine synthase, an enzyme that catalyzes the fourth step in the de novo biosynthesis of purines. In some species of bacteria and rchaea, FGAM synthase II is composed of two subunits: a small chain (gene purQ) which provides the GATase activity and a large chain (gene purL) which provides the aminator activity. In eukaryotes and Gram-negative bacteria a single polypeptide (large type of purL) contains a FGAM synthethase domain and the GATase as the C-terminal domain [
].Imidazole glycerol phosphate synthase subunit hisH, an enzyme that catalyzes the fifth step in the biosynthesis of histidine.A triad of conserved Cys-His-Glu forms the active site, wherein the catalytic cysteine is essential for the amidotransferase activity [
,
]. Different structures show that the active site Cys of type 1 GATase is located at the tip of a nucleophile elbow.
This entry represents the TIM β/α barrel found in aldolase and in related proteins. This TIM barrel usually covers the entire protein structure. Proteins containing this TIM barrel domain include class I aldolases, class I DAHP synthases, class II fructose-bisphosphate aldolases (FBP aldolases), and 5-aminolevulinate dehydratase (a hybrid of classes I and II aldolases) [
,
,
].
Imidazole glycerol phosphate synthetase (IGPS) is a key metabolic enzyme, which links amino acid and nucleotide biosynthesis: it catalyses the closure of the imidazole ring within histidine biosynthesis (fifth step), and provides the substrate for de novo purine biosynthesis. IGPS consists of two different subunits: HisH, a glutamine amidotransferase (glutaminase), and HisF, a synthase (cyclase). HisH functions to provide a source of nitrogen, which is required for the synthesis of histidine and purines. In the HisH glutaminase reaction, the hydrolysis of glutamine yields ammonia, which is then used by HisF in the subsequent synthase reaction. The X-ray structure of the HisH/HisF heterodimer of IGPS reveals a putative tunnel for the transfer of ammonia from HisH to HisF via a (beta-alpha)8 barrel fold within HisF that abuts HisH [
]. Ammonia tunnels connect the glutaminase and synthase active sites.HisH belongs to a large group of enzymes found in diverse and fundamental anabolic pathways. These enzymes share a common domain, referred to as the type-I glutamine amidotransferase (GATase) domain, which can occur either as single polypeptides (as with HisH) or as domains of large multifunctional proteins.
The ribulose-phosphate binding barrel consists of a parallel β-sheet barrel fold containing a phosphate-binding site. Several proteins display this fold, including histidine biosynthesis enzymes, tryptophan biosynthesis enzymes, D-ribulose-5-phosphate 3-epimerase, and decarboxylases [
].
Histidine is formed by several complex and distinct biochemical reactions catalysed by eight enzymes. Proteins involved in steps 4 and 6 of the histidine biosynthesis pathway are contained in one family. These enzymes are called His6 and His7 in eukaryotes and HisA and HisF in prokaryotes. HisA is a phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase (
), involved in the fourth step of histidine biosynthesis. The bacterial HisF protein is a cyclase which catalyses the cyclization reaction that produces D-erythro-imidazole glycerol phosphate during the sixth step of histidine biosynthesis. The yeast His7 protein is a bifunctional protein which catalyses an amido-transferase reaction that generates imidazole-glycerol phosphate and 5-aminoimidazol-4-carboxamide. The latter is the ribonucleotide used for purine biosynthesis. The enzyme also catalyses the cyclization reaction that produces D-erythro-imidazole glycerol phosphate, and is involved in the fifth and sixth steps in histidine biosynthesis.
Members of this group are eukaryotic bifunctional enzymes with glutamine amidotransferase (
) and cyclase activities (
) that catalyse the fifth and sixth steps of the histidine biosynthetic pathway. In eubacteria, these steps are catalysed by a complex formed by two subunits, namely the glutamine amidotransferase HisH (
) and the cyclase HisF which are encoded in the same operon [
].The catalytic activity has been assessed for many members, mainly by complementation assays. The Saccharomyces cerevisiae (Baker's yeast) member is able to suppress His auxotrophy of corresponding Escherichia coli hisH and hisF mutants [
]. In plants, hisHF cDNA from Emericella nidulans (Aspergillus nidulans) and Arabidopsis thaliana (Mouse-ear cress) complemented a S. cerevisiae his7Deltastrain [
,
]. In addition, A. nidulans cDNA complemented E. coli hisHand
hisFmutant strains [
].
Archaeal and eukaryotic translation elongation factor 2 contain a unique posttranslationally modified histidine residue called diphthamide, the target of the diphtheria toxin. Diphtheria toxin inhibits eukaryotic protein synthesis by ADP-ribosylating diphthamide in EF2 [
].Members of this family include 2-(3-amino-3-carboxypropyl)histidine synthase subunit 1/2 (also known as Diphtheria toxin resistance protein 1/2, DPH 1/2), which are involved in the first step of diphthamide synthesis [
,
]. Archaeal DPHs are more similar to eukaryotic DPH1 than to DPH2 [].
This family consists of several plant proteins of unknown function, including pathogen-associated molecular patterns-induced protein A70 from Arabidopsis thaliana, which is induced during Pseudomonas syringae infection by jasmonic acid and wounding [
].
This domain of unknown function is found at the N-terminal of the pathogen-associated molecular patterns-induced protein A70 from Arabidopsis thaliana and other plant proteins.
This entry includes CCR4-NOT transcription complex subunit 9 (CNOT9 or Rcd1). Mammalian CNOT9 is a component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation [
].
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.Enzymes containing this domain, such as alpha-amylase, belong to family 13 (
) of the glycosyl hydrolases. The maltogenic alpha-amylase is an enzyme which catalyses hydrolysis of (1-4)-alpha-D-glucosidic linkages in polysaccharides so as to remove successive alpha-maltose residues from the non-reducing ends of the chains in the conversion of starch to maltose. Other enzymes include neopullulanase, which hydrolyses pullulan to panose, and cyclomaltodextrinase, which hydrolyses cyclodextrins.
This entry represents the catalytic domain found in several protein members of this family. It has a structure consisting of an 8 stranded α/β barrel that contains the active site, interrupted by a ~70 amino acid calcium-binding domain protruding between β-strand 3 and α-helix 3, and a carboxyl-terminal Greek key β-barrel domain [
].
Alpha-amylase/branching enzyme, C-terminal all beta
Type:
Domain
Description:
This entry represents the all-beta C-terminal domain that is found in members of the glycosyl hydrolase 13 family, such as alpha-amylases and 1,4-alpha-glucan branching enzyme. This domain forms a Greek key β-barrel fold in these enzymes [
].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. Branching enzyme catalyses the formation of alpha-1,6 branch points in either glycogen or starch. It has an important role in the determination of the structure of starch in plants and of glycogen in animals and bacteria [
].
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.This entry represents the all-β domain superfamily that is found in several members of the glycosyl hydrolase family 13 and other glycosyl hydrolases. It is usually located C-terminal to the catalytic β/α barrel domain. The structure of this domain has been found to be a Greek key β-sheet fold [
,
,
,
].
This family is named after YEATS (Yaf9, ENL, AF9, Taf14, and Sas5), an evolutionarily conserved module present in 4 proteins (ENL, AF9, GAS41, and YEATS2) in humans and 3 proteins (Sas5, Taf14, and Yaf9) in yeast. These proteins are found in major chromatin-remodeling and histone acetyl-transferase (HAT) complexes and implicated in regulation of chromatin structure, histone acetylation and deposition, gene transcription and DNA damage response. The YEATS domain, which as previously shown is found in a number of chromatin-associated proteins, has recently been shown to have the capacity to bind histone lysine acetylation [
]. The ability of the YEATS domains of human AF9 and yeast Taf14 to recognise the histone mark H3K9ac, have shown that these proteins are members of the family of acetyllysine readers [].
Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, is an essential cofactor for nearly 60 Escherichia coli enzymes and 140 human enzymes. It is a highly reactive molecule that is toxic in its free form. The E. coli PROSC, known as yggS, binds to PLP and is involved in PLP homeostasis, supplying this cofactor to apoenzymes while minimizing any toxic side reactions [
,
]. Proteins in this entry occur in archaea, bacteria and eukaryotes. The bacterial proteins are co-transcribed with proline biosysnthesis genes, hence this group of proteins are also named the proline synthetase co-transcribed homologues (PROSC) [
].The structure of the yeast protein (
) has been determined to a resolution of 2.0 A [
]. Similar in structure to the N-terminal domains of alanine racemase and ornithine decarboxylase, it forms a TIM barrel fold which begins with a long N-terminal helix, rather than the classical beta strand found at the beginning of most other TIM barrels. Unlike alanine racemase and ornithine decarboxylase, which are two-domain dimeric proteins, the yeast protein is a single domain monomer. A pyridoxal 5'-phosphate cofactor is covalently bound towards the C-terminal end of the barrel, which is the usual active site in TIM-barrel folds. Some racemase activity was observed for this protein and it was suggested by the authors that it may function as a general racemase [].
Alanine racemase plays a role in providing the D-alanine required for cell wall biosynthesis by isomerising L-alanine to D-alanine.The molecular structure of alanine racemase from Bacillus stearothermophilus was determined by X-ray crystallography to a resolution of 1.9 A [
]. The alanine racemase monomer is composed of two domains, an eight-stranded alpha/beta barrel at the N terminus, and a C-terminal domain essentially composed of β-strands. The pyridoxal 5'-phosphate (PLP) cofactor lies in and above the mouth of the alpha/beta barrel and is covalently linked via an aldimine linkage to a lysine residue, which is at the C terminus of the first β-strand of the alpha/beta barrel.This N-terminal domain is also found in the PROSC (proline synthetase co-transcribed bacterial homologue) family of proteins, which are not known to have alanine racemase activity.
This entry represents a domain found towards the N-terminal region of mandelate racemase and muconate lactonizing enzyme. These enzymes share a bidomain structure containing a capping domain and a C-terminal barrel domain. The N-terminal domain forms part of the capping domain [
]. This domain is also found in a variety of other enzymes, including D-galactonate dehydratase and D-mannonate dehydratase.
Methyl transfer from the ubiquitous S-adenosyl-L-methionine (SAM) to either nitrogen, oxygen or carbon atoms is frequently employed in diverse organisms ranging from bacteria to plants and mammals. The reaction is catalyzed by methyltransferases (Mtases) and modifies DNA, RNA, proteins and small molecules, such as catechol for regulatory purposes. The various aspects of the role of DNA methylation in prokaryotic restriction-modification systems and in a number of cellular processes in eukaryotes including gene regulation and differentiation is well documented.This entry represents a methyltransferase domain found in a large variety of SAM-dependent methyltransferases including, but not limited to:
Arsenite methyltransferase (
) which converts arsenical compounds to their methylated forms [
]
Biotin synthesis protein bioC, which is involved in the early stages of biotin biosyntheis [
]
Arginine N-methyltransferase 1, an arginine-methylating enzyme which acts on residues present in a glycine and argine-rich domain and can methylate histones [
]
Hexaprenyldihydroxybenzoate methyltransferase (
), a mitochodrial enzyme involved in ubiquinone biosynthesis [
]
A probable cobalt-precorrin-6Y C(15)-methyltransferase thought to be involved in adenosylcobalamin biosynthesis [
]
Sterol 24-C-methyltransferase (
), shown to participate in ergosterol biosynthesis [
]
3-demethylubiquinone-9 3-methyltransferase (
) involved in ubiquinone biosynthesis [
]
Structural studies show that this domain forms the Rossman-like α-β fold typical of SAM-dependent methyltransferases [,
,
].
This representative of this family is the STIG1 cysteine rich protein. The tobacco stigma-specific gene, STIG1 is developmentally regulated and expressed specifically in the stigmatic secretory zone. Pistils of transgenic STIG1-barnase tobacco plants undergo normal development, but lack the stigmatic secretory zone and are female sterile. Pollen grains are unable to penetrate the surface of the ablated pistils. Application of stigmatic exudate from wild-type pistils to the ablated surface increases the efficiency of pollen tube germination and growth and restores the capacity of pollen tubes to penetrate the style [
]. The function of STIG1 is unknown.
The WRKY domain is a 60 amino acid region that is defined by the conserved amino acid sequence WRKYGQK at its N-terminal end, together with a novel zinc-finger-like motif. The WRKY domain is found in one or two copies in a superfamily of plant transcription factors involved in the regulation of various physiological programs that are unique to plants, including pathogen defence, senescence, trichome development and the biosynthesis of secondary metabolites. The WRKY domain binds specifically to the DNA sequence motif (T)(T)TGAC(C/T), which is known as the W box. The invariant TGAC core of the W box is essential for function and WRKY binding [
]. Some proteins known to contain a WRKY domain include Arabidopsis thaliana ZAP1 (Zinc-dependent Activator Protein-1) and AtWRKY44/TTG2, a protein involved in trichome development and anthocyanin pigmentation; and wild oat ABF1-2, two proteins involved in the gibberelic acid-induced expression of the alpha-Amy2 gene.Structural studies indicate that this domain is a four-stranded β-sheet with a zinc binding pocket, forming a novel zinc and DNA binding structure [
]. The WRKYGQK residues correspond to the most N-terminal β-strand, which enables extensive hydrophobic interactions, contributing to the structural stability of the β-sheet.
This entry includes small ubiquitin-related modifier (SUMO) proteins. SUMOs are small proteins that are covalently attached to lysines as post-translational modifications and are used to control multiple cellular process including signal transduction, nuclear transport and DNA replication and repair [
]. Unlike ubiquitin, they are not involved in protein degradation. This entry also contains the C-terminal Rad60 DNA repair protein SUMO-like domain.
The G-patch domain is an approximately 48 amino acid domain, which is found in
a single copy in several RNA-associated proteins and in type D retroviralpolyproteins. It is widespread among eukaryotes but is absent in archaea and
bacteria. The G-patch domain has been called after its most notable feature,the presence of six highly conserved glycine residues. The position following
the first conserved glycine is occupied almost invariably by an aromaticresidue, and several other positions are occupied predominantly by either
hydrophobic or small residues. Several groups of G-patch containing proteinsare conserved in animals, plants and fungi. In some of these proteins the G-
patch is the only recognisable domain but in most of them it is combined withother domains, which include well-defined RNA-binding domains, such as the
RRM, dsRBD, SURP and R3H. It has been suggested that the G-patch domain has a specific function in RNA processing and, in particular, that it might be a previously
undetected RNA-binding domain mediating a distinct type of RNA-protein interaction.Secondary structure prediction indicates that the G-patch domain probably
contains two α-helices, with four out of the six glycines located withinan intervening loop.
Proteins known to contain a G-patch domain include:Eukaryotic 45kDa splicing factor (SPF-45).Mammmalian SON protein, a DNA-binding protein.Human LUCA15, a multidomain RNA-binding protein that is the product of a gene deleted in certain lung tumors.Human DAN26/EPROT, a multidomain protein, which, in addition to the G-patch domain, contains an RNA polymerase II C-terminal repeat-binding domain seen in many proteins of the polyA-addition machinery.Arabidopsis thaliana DRT111, a protein which has been shown to partially restore recombination proficiency and DNA-damage resistance to E. coli mutants.Type D retroviral polyprotein, where the G-patch domain is found directly downstream of the protease domain.
Calcineurin-like phosphoesterase domain, ApaH type
Type:
Domain
Description:
This domain is found in a diverse range of phosphoesterases [
], including bis(5'-nucleosyl)-tetraphosphatase (apaH), nucleotidases, sphingomyelin phosphodiesterases and 2'-3' cAMP phosphodiesterases, as well as nucleases such as bacterial SbcD or archaeal/yeast Mre11. The most conserved regions in this domain centre around the metal chelating residues.
This entry includes purple acid phosphatases (EC 3.1.3.2), which are metal dependent, binding two metal ions. Metal binding ligands and residues involved in resistance to tartrate inhibition are conserved [
].Purple acid phosphatase 3, 4, 7, 8 and 17 are found in plants, bind zinc and iron, and the genes are predominantly transcribed in flowers [
]. Purple acid phosphatase 17 (PAP17) is induced in response to phosphate starvation, a condition occurring in phosphate-poor soils, and the plant hormone abscisic acid (ABA) and salt stress. Like mammalian acid phosphatase 5, PAP17 has peroxidation activity [].Acid phosphatase 5 (ACP5; EC 3.1.3.2) removes the mannose 6-phosphate recognition marker from lysosomal proteins. The exact site of dephosphorylation is not clear. Evidence suggests dephosphorylation may take place in a prelysosomal compartment as well as in the lysosome [
]. ACP5 belongs to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain with an active site consisting of two metal ions (usually manganese, iron, or zinc) co-ordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues [].
Mammalian prolyl 4-hydroxylase alpha catalyses the posttranslational formation of 4-hydroxyproline in -xaa-pro-gly-sequences in collagens and other proteins. Prokaryotic enzymes might catalyse hydroxylation of antibiotic peptides. These are 2-oxoglutarate-dependent dioxygenases, requiring 2-oxoglutarate and dioxygen as cosubstrates and ferrous iron as a cofactor [
].
A variety of isoprenoid compounds are synthesized by various organisms. For example in eukaryotes the isoprenoid biosynthetic pathway is responsible for the synthesis of a variety of end products including cholesterol, dolichol, ubiquinone or coenzyme Q. In bacteria this pathway leads to the synthesis of isopentenyl tRNA, isoprenoid quinones, and sugar carrier lipids. Among the enzymes that participate in that pathway, are a number of polyprenyl synthetase enzymes which catalyze a 1'4-condensation between 5 carbon isoprene units.It has been shown [
,
,
,
,
] that these enzymes share some regions of sequence similarity. From 3D structure analysis, it was revealed that they also share structure and reaction mechanisms, using similar strategies for substrate binding and catalysis [].
This superfamily represents a domain found in the isoprenoid synthase family [
], which is mostly all α-helical with a core bundle of anti-parallel α-helices [].
Plant cells contain proteins, called non-specific lipid-transfer proteins (nsLTPs) [
,
,
,
], which transfer phospholipids, glycolipids, fatty acids and sterols from liposomes or microsomes to mitochondria [] and are thought to be involved in plant defense. These proteins, expressed throughout the plant tissues but predominantly found in edible parts [], could play a major role in membrane biogenesis by conveying phospholipids such as waxes or cutin from their site of biosynthesis to membranes unable to form these lipids. LTPs exist in animal and plant tissues, including rat liver cytosol, potato tuber, castor bean, maize seedlings, spinach, barley and wheat. While there is no sequence similarity between animal and plant LTPs, similarity between the plant proteins is high. Plant LTPs are proteins of about 9 Kd (90 amino acids), containing eight conserved cysteine residues forming 4 disulphide bridges which allow to form a stable, compact barrel-like structure, which is essential for lipid binding []. Plant TLPs are also similar to alpha-amylase inhibitor I2 from the seeds of Indian finger millet and amylase/protease inhibitors from rice and barley.Some of the proteins in this family are allergens. Allergies are hypersensitivity reactions of the immune system to specific substances called allergens (such as pollen, stings, drugs, or food) that, in most people, result in no symptoms. A nomenclature system has been established for antigens (allergens) that cause IgE-mediated atopic allergies in humans [WHO/IUIS Allergen Nomenclature Subcommittee King T.P., Hoffmann D., Loewenstein H., Marsh D.G., Platts-Mills T.A.E., Thomas W. Bull. World Health Organ. 72:797-806(1994)]. This nomenclature system is defined by a designation that is composed of the first three letters of the genus; a space; the first letter of the species name; a space and an arabic number. In the event that two species names have identical designations, they are discriminated from one another by adding one or more letters (as necessary) to each species designation.The allergens in this family include allergens with the following designations: Par j 1 and Par j 2.
Gibberellins are plant hormones which have great impact on growth signalling. DELLA proteins are transcriptional regulators of growth related proteins that lack a DNA binding domain and exert its negative regulation of gibberellin responses through interaction with other transcription factors [
]. DELLAs are downregulated when gibberellins bind to their receptor GID1 [,
], which forms a complex with DELLA proteins and signals them towards 26S proteasome. The N-terminal of DELLA proteins contains conserved DELLA and TVHYNP motifs which are important for GID1 binding and proteolysis of the DELLA proteins [,
].
Sequence analysis of the products of the GRAS (GAI, RGA, SCR) gene family indicates that they share a variable N terminus and a highly conserved C terminus that contains five recognizable motifs [
]. Proteins in the GRAS family are major players in gibberellin (GA) signaling, which regulates various aspects of plant growth and development []. Mutation of the SCARECROW (SCR) gene results in a radial pattern defect, loss of a ground tissue layer, in the root. The PAT1 protein is involved in phytochrome A signal transduction [].A sequence, structure and evolutionary analysis showed that the GRAS family emerged in bacteria and belongs to the Rossmann-fold, AdoMET (SAM)-dependent methyltransferase superfamily [
]. All bacterial, and a subset of plant GRAS proteins, are predicted to be active and function as small-molecule methylases. Several plant GRAS proteins lack one or more AdoMet (SAM)-binding residues while preserving their substrate-binding residues. Although GRAS proteins are implicated to function as transcriptional factors, the above analysis suggests that they instead might either modify or bind small molecules [].Some proteins known to belong to the GRAS family are listed below:
Arabidopsis thaliana SCARECROW (SCR) protein. It regulates asymetric cell divisions of cortex/endodermal initial cells during root development.Arabidopsis thaliana SCARECROW-LIKE (SCL) protein.Arabidopsis thaliana GIBBERELLIN-ACID INSENSITIVE (GAI) and REPRESSOR OF
GA1 (RGA), two closely related proteins involved in gibberellin signaling.Arabidopsis thaliana SHORT ROOT (SHR) protein. It is necessary for cell
division and endodermis specification.Arabidopsis thaliana PAT1 protein. It inhibits light signaling via the
phytochrome A (phyA).LATERAL SUPPRESSOR (LS), a protein from tomato that controls the formation
of lateral branches during vegetative development.
This family of transmembrane proteins are functionally uncharacterised. This protein is found in eukaryotes. Proteins in this family are typically between 427 to 453 amino acids in length.
Zinc fingers are a ubiquitous class of protein domain with considerable variation in structure and function. The FCS-type zinc finger is a highly diverged group of C2-C2 zinc finger which is present in animals, prokaryotes and viruses, but not in plants. It is named after the conserved phenylalanine and serine residues associated with the third cysteine. The FCS-type zinc finger is a structurally diverse family which accommodate both nucleic-protein and protein-protein interaction zinc fingers. The FCS-Like Zinc finger (FLZ) domain is a plant specific domain found in all taxa except algae. FLZ domain containing proteins are bryophytic in origin and this protein family is expanded in higher plants. Although the molecular functions of the FLZ protein family members in general are not well understood, many of the members are attributed to plant growth and development, stress mitigation, sugar signaling and senescence. The FLZ-type zinc finger is likely to be involved in protein-protein interaction [
,
,
].The FLZ-type zinc finger is predicted to form an α-β-alpha secondary structure composed of an N-terminal short α-helix, a beta hairpin followed by a longer C-terminal alpha helix. Four highly conserved cysteine residues in the FLZ-type zinc finger are believed to bind zinc in a tetrahedral coordination [
,
].Some proteins known to contain a FLZ-type zinc finger are listed below [
]:Arabidopsis thaliana MEDIATOR OF ABA-REGULATED DORMANCY 1 (MARD1) or FLZ9, involved in absissic acid (ABA)-mediated seed dormancy and induced during senescence.Arabidopsis thaliana INCREASED RESISTANCE TO MYZUS PERSICAE (IRM1) or FLZ4, constitutive overexpression of IRM1 results in mechanical barriers that make it difficult for M. persicae to reach the phloem and subsequently reduces its population size.Wheat salt related hypothetical protein (TaSRHP), overexpression of TaSHRP results in enhanced resistance to salt and drought stress.
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [
,
,
,
,
]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. This entry represents a zinc finger motif found in transcription factor IIB (TFIIB). In eukaryotes the initiation of transcription of protein encoding genes by the polymerase II complexe (Pol II) is modulated by general and specific transcription factors. The general transcription factors operate through common promoters elements (such as the TATA box). At least seven different proteins associate to form the general transcription factors: TFIIA, -IIB, -IID, -IIE, -IIF, -IIG, and -IIH [
].TFIIB and TFIID are responsible for promoter recognition and interaction with pol II; together with Pol II, they form a minimal initiation complex capable of transcription under certain conditions. The TATA box of a Pol II promoter is bound in the initiation complex by the TBP subunit of TFIID, which bends the DNA around the C-terminal domain of TFIIB whereas the N-terminal zinc finger of TFIIB interacts with Pol II [
,
].The TFIIB zinc finger adopts a zinc ribbon fold characterised by two β-hairpins forming two structurally similar zinc-binding sub-sites [
]. The zinc finger contacts the rbp1 subunit of Pol II through its dock domain, a conserved region of about 70 amino acids located close to the polymerase active site []. In the Pol II complex this surface is located near the RNA exit groove. Interestingly this sequence is best conserved in the three polymerases that utilise a TFIIB-like general transcription factor (Pol II, Pol III, and archaeal RNA polymerase) but not in Pol I [].
Molecular chaperones are a diverse family of proteins that function to protect proteins in the intracellular milieu from irreversible aggregation during synthesis and in times of cellular stress. The bacterial molecular chaperone DnaK is an enzyme that couples cycles of ATP binding, hydrolysis, and ADP release by an N-terminal ATP-hydrolysing domain to cycles of sequestration and release of unfolded proteins by a C-terminal substrate binding domain. DnaK is itself a weak ATPase; ATP hydrolysis by DnaK is stimulated by its interaction with another co-chaperone, DnaJ. In prokaryotes the dimeric GrpE is the co-chaperone for DnaK, and acts as a nucleotide exchange factor, stimulating the rate of ADP release 5000-fold [
]. GrpE participates actively in response to heat shock by preventing aggregation of stress-denatured proteins: unfolded proteins initially bind to DnaJ, the J-domain ATPase-activating protein (Hsp40 family), whereupon DnaK hydrolyzes its bound ATP, resulting in a stable complex. The GrpE dimer binds to the ATPase domain of Hsp70 catalyzing the dissociation of ADP, which enables rebinding of ATP, one step in the Hsp70 reaction cycle in protein folding. Thus the co-chaperones DnaJ and GrpE are capable of tightly regulating the nucleotide-bound and substrate-bound state of DnaK in ways that are necessary for the normal housekeeping functions and stress-related functions of the DnaK molecular chaperone cycle [,
,
,
,
,
,
,
,
].In eukaryotes, only the mitochondrial Hsp70, not the cytosolic form, is GrpE dependent. Over-expression of Hsp70 molecular chaperones is important in suppressing toxicity of aberrantly folded proteins that occur in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, as well as several polyQ-diseases such as Huntington's disease and ataxias.The X-ray crystal structure of GrpE in complex with the ATPase domain of DnaK revealed that GrpE is an asymmetric homodimer, bent in a manner that favours extensive contacts with only one DnaK
ATPasemonomer [
]. GrpE does not actively compete for the atomic positions occupied by the nucleotide. GrpE and ADP mutually reduce one another's affinity for DnaK 200-fold, and ATP instantly dissociates GrpE from DnaK.
In prokaryotes, the nucleotide exchange factor GrpE and the chaperone DnaJ are required for nucleotide binding of the molecular chaperone DnaK [
]. The DnaK reaction cycle involves rapid peptide binding and release, which is dependent upon nucleotide binding. DnaJ accelerates the hydrolysis of ATP by DnaK, which enables the ADP-bound DnaK to tightly bind peptide. GrpE catalyses the release of ADP from DnaK, which is required for peptide release. In eukaryotes, GrpE is essential for mitochondrial Hsp70 function, however the cytosolic Hsp70 homologues are GrpE-independent.GrpE binds as a homodimer to the ATPase domain of DnaK, and may interact with the peptide-binding domain of DnaK. GrpE accomplishes nucleotide exchange by opening the nucleotide-binding cleft of DnaK. GrpE is comprised of two domains, the N-terminal coiled coil domain, which may facilitate peptide release, and the C-terminal head domain, which forms part of the contact surface with the ATPase domain of DnaK. This superfamily represents the N-terminal coiled-coil domain.
In prokaryotes, the nucleotide exchange factor GrpE and the chaperone DnaJ are required for nucleotide binding of the molecular chaperone DnaK [
]. The DnaK reaction cycle involves rapid peptide binding and release, which is dependent upon nucleotide binding. DnaJ accelerates the hydrolysis of ATP by DnaK, which enables the ADP-bound DnaK to tightly bind peptide. GrpE catalyses the release of ADP from DnaK, which is required for peptide release. In eukaryotes, GrpE is essential for mitochondrial Hsp70 function, however the cytosolic Hsp70 homologues are GrpE-independent.GrpE binds as a homodimer to the ATPase domain of DnaK, and may interact with the peptide-binding domain of DnaK. GrpE accomplishes nucleotide exchange by opening the nucleotide-binding cleft of DnaK. GrpE is comprised of two domains, the N-terminal coiled coil domain, which may facilitate peptide release, and the C-terminal head domain, which forms part of the contact surface with the ATPase domain of DnaK. The head domain is comprised of six short beta strands with a limited hydrophobic core.
This entry represents N-terminal acetyltransferase A (NatA) auxiliary subunit, which is a non-catalytic component of the NatA N-terminal acetyltransferase that catalyses acetylation of proteins beginning with Met-Ser, Met-Gly and Met-Ala. N-terminal acetylation plays a role in normal eukaryotic translation and processing, protecting against proteolytic degradation and protein turnover. NAT1 anchors ARD1 and NAT5 to the ribosome, and may present the N terminus of nascent polypeptides for acetylation [
,
].
Cullins are a family of hydrophobic proteins that act as scaffolds for ubiquitin ligases (E3). Cullins are found throughout eukaryotes. Humans express seven cullins (Cul1, 2, 3, 4A, 4B, 5 and 7), each forming part of a multi-subunit ubiquitin complex. Cullin-RING ubiquitin ligases (CRLs), such as Cul1 (SCF) [
], play an essential role in targeting proteins for ubiquitin-mediated destruction; as such, they are diverse in terms of composition and function, regulating many different processes from glucose sensing and DNA replication to limb patterning and circadian rhythms. The catalytic core of CRLs consists of a RING protein and a cullin family member. For Cul1, the C-terminal cullin-homology domain binds the RING protein. The RING protein appears to function as a docking site for ubiquitin-conjugating enzymes (E2s). Other proteins contain a cullin-homology domain, such as the APC2 subunit of the anaphase-promoting complex/cyclosome and the p53 cytoplasmic anchor PARC; both APC2 and PARC have ubiquitin ligase activity. The N-terminal region of cullins is more variable, and is used to interact with specific adaptor proteins [,
,
].This entry represents the N-terminal region of cullin proteins, which consists of several domains, including cullin repeat domain, a 4-helical bundle domain, an alpha+beta domain, and a winged helix-like domain.
Cullins are a family of hydrophobic proteins that act as scaffolds for ubiquitin ligases (E3). Cullins are found throughout eukaryotes. Humans express seven cullins (Cul1, 2, 3, 4A, 4B, 5 and 7), each forming part of a multi-subunit ubiquitin complex. Cullin-RING ubiquitin ligases (CRLs), such as Cul1 (SCF) [
], play an essential role in targeting proteins for ubiquitin-mediated destruction; as such, they are diverse in terms of composition and function, regulating many different processes from glucose sensing and DNA replication to limb patterning and circadian rhythms. The catalytic core of CRLs consists of a RING protein and a cullin family member. For Cul1, the C-terminal cullin-homology domain binds the RING protein. The RING protein appears to function as a docking site for ubiquitin-conjugating enzymes (E2s). Other proteins contain a cullin-homology domain, such as the APC2 subunit of the anaphase-promoting complex/cyclosome and the p53 cytoplasmic anchor PARC; both APC2 and PARC have ubiquitin ligase activity. The N-terminal region of cullins is more variable, and is used to interact with specific adaptor proteins [,
,
].This entry represents a conserved site found in various cullin proteins.
This is the neddylation site of cullin proteins, which are a family of structurally related proteins containing an evolutionarily conserved cullin domain. With the exception of APC2, each member of the cullin family is modified by Nedd8 and several cullins function in Ubiquitin-dependent proteolysis, a process in which the 26S proteasome recognises and subsequently degrades a target protein tagged with K48-linked poly-ubiquitin chains. Cullins are molecular scaffolds responsible for assembling the ROC1/Rbx1 RING-based E3 ubiquitin ligases, of which several play a direct role in tumorigenesis. Nedd8/Rub1 is a small ubiquitin-like protein, which was originally found to be conjugated to Cdc53, a cullin component of the SCF (Skp1-Cdc53/CUL1-F-box protein) E3 Ub ligase complex in Saccharomyces cerevisiae (Baker's yeast), and Nedd8 modification has now emerged as a regulatory pathway of fundamental importance for cell cycle control and for embryogenesis in metazoans. The only identified Nedd8 substrates are cullins. Neddylation results in covalent conjugation of a Nedd8 moiety onto a conserved cullin lysine residue [
].
Cullins are a family of hydrophobic proteins that act as scaffolds for ubiquitin ligases (E3). Cullins are found throughout eukaryotes. Humans express seven cullins (Cul1, 2, 3, 4A, 4B, 5 and 7), each forming part of a multi-subunit ubiquitin complex. Cullin-RING ubiquitin ligases (CRLs), such as Cul1 (SCF) [
], play an essential role in targeting proteins for ubiquitin-mediated destruction; as such, they are diverse in terms of composition and function, regulating many different processes from glucose sensing and DNA replication to limb patterning and circadian rhythms. The catalytic core of CRLs consists of a RING protein and a cullin family member. For Cul1, the C-terminal cullin-homology domain binds the RING protein. The RING protein appears to function as a docking site for ubiquitin-conjugating enzymes (E2s). Other proteins contain a cullin-homology domain, such as the APC2 subunit of the anaphase-promoting complex/cyclosome and the p53 cytoplasmic anchor PARC; both APC2 and PARC have ubiquitin ligase activity. The N-terminal region of cullins is more variable, and is used to interact with specific adaptor proteins [,
,
].
Cullins are a family of hydrophobic proteins that act as scaffolds for ubiquitin ligases (E3). Cullins are found throughout eukaryotes. Humans express seven cullins (Cul1, 2, 3, 4A, 4B, 5 and 7), each forming part of a multi-subunit ubiquitin complex. Cullin-RING ubiquitin ligases (CRLs), such as Cul1 (SCF) [
], play an essential role in targeting proteins for ubiquitin-mediated destruction; as such, they are diverse in terms of composition and function, regulating many different processes from glucose sensing and DNA replication to limb patterning and circadian rhythms. The catalytic core of CRLs consists of a RING protein and a cullin family member. For Cul1, the C-terminal cullin-homology domain binds the RING protein. The RING protein appears to function as a docking site for ubiquitin-conjugating enzymes (E2s). Other proteins contain a cullin-homology domain, such as the APC2 subunit of the anaphase-promoting complex/cyclosome and the p53 cytoplasmic anchor PARC; both APC2 and PARC have ubiquitin ligase activity. The N-terminal region of cullins is more variable, and is used to interact with specific adaptor proteins [,
,
].This superfamily represents the N-terminal cullin repeat-containing domain; these repeats form a domain with a multi-helical 2-layered alpha/alpha structure, which in turn is folded into a right-handed superhelix. A similar structural domain is found in exocyst complex components such as EXO70 and EXO84.
Carotenoids such as beta-carotene, lycopene, lutein and beta-cryptoxanthine are produced in plants and certain bacteria, algae and fungi, where they function as accessory photosynthetic pigments and as scavengers of oxygen radicals for photoprotection. They are also essential dietary nutrients in animals. Carotenoid oxygenases cleave a variety of carotenoids into a range of biologically important products, including apocarotenoids in plants that function as hormones, pigments, flavours, floral scents and defence compounds, and retinoids in animals that function as vitamins, visual pigments and signalling molecules [
]. Examples of carotenoid oxygenases include:Beta,beta-carotene 15,15'-dioxygenase (BCDO1) from animals, which cleaves beta-carotene symmetrically at the central double bond to yield two molecules of retinal [
].Carotenoid-cleaving dioxygenase, mitochondrial (BCDO2) from animals, which cleaves beta-carotene asymmetrically to apo-10'-beta-carotenal and beta-ionone, the latter being converted to retinoic acid. Lycopene is also oxidatively cleaved [
,
,
].Carotenoid 9,10(9',10')-cleavage dioxygenase (CCD) from plants, which cleaves a variety of carotenoids symmetrically at both the 9-10 and 9'-10' double bonds and catalyzes the formation of 4,9-dimethyldodeca-2,4,6,8,10-pentaene-1,12-dialdehyde from zeaxanthin [
]. 9-cis-epoxycarotenoid dioxygenase (NCED1/2) from plants, which cleaves 9-cis xanthophylls to xanthoxin, a precursor of the hormone abscisic acid [
].Apocarotenoid-15,15'-oxygenase (ACOX) from bacteria and cyanobacteria, which converts beta-apocarotenals rather than beta-carotene into retinal. This protein has a seven-bladed β-propeller structure with four hisitidines that hold the iron active centre [
].Retinoid isomerohydrolase (RPE65) from animals, which in its soluble form binds all-trans retinol, and in its membrane-bound form binds all-trans retinyl esters. RPE65 is important for the production of 11-cis retinal during visual pigment regeneration [
,
,
].
The tify domain is a 36-amino acid domain only found among Embryophyta (land plants). It has been named after the most conserved amino acid pattern (TIF[F/Y]XG) it contains, but was previously known as the Zim domain. As the use of uppercase characters (TIFY) might imply that the domain is fully conserved across proteins, a lowercase lettering has been chosen in an attempt to highlight the reality of its natural variability. Based on the domain architecture, tify domain containing proteins can be classified into two groups. Group I is formed by proteins possessing a CCT (CONSTANS, CO-like, and TOC1) domain and a GATA-type zinc finger in addition to the tify domain. Group II contains proteins characterised by the tify domain but lacking a GATA-type zinc finger. Tify domain containing proteins might be involved in developmental processes and some of them have features that are characteristic for transcription factors: a nuclear localisation and the presence of a putative DNA-binding domain [
]. Some proteins known to contain a tify domain include: Arabidopsis thaliana GATA transcription factors (Zinc-finger protein expressed in Inflorescence Meristem, ZIM), a putative transcription factor involved in inflorescence and flower development [
,
]. A. thaliana ZIM-like proteins (ZML) [
]. A. thaliana Protein TIFY 1-11 [
].
The short CCT (CO, COL, TOC1) motif is found in a number of plant proteins, including Constans (CO), Constans-like (COL) and TOC1. The CCT motif is about 45 amino acids long and contains a putative nuclear localisation signal within the second half of the CCT motif [
]. The CCT motif is found in the Arabidopsis circadian rhythm protein TOC1, an autoregulatory response regulator homologue the controls the photoperiodic flowering through its clock function [].
A number of oxidoreductases that act on alpha-hydroxy acids and which are FMN-containing flavoproteins have been shown [
,
,
] to be structurally related. These enzymes are:Lactate dehydrogenase (
), which consists of a dehydrogenase domain and a haem-binding domain called cytochrome b2 and which catalyses the conversion of lactate into pyruvate.
Glycolate oxidase (
) ((S)-2-hydroxy-acid oxidase), a peroxisomal enzyme that catalyses the conversion of glycolate and oxygen to glyoxylate and hydrogen peroxide.
Long chain alpha-hydroxy acid oxidase from rat (
), a peroxisomal enzyme.
Lactate 2-monooxygenase (
) (lactate oxidase) from Mycobacterium smegmatis, which catalyses the conversion of lactate and oxygen to acetate, carbon dioxide and water.
(S)-mandelate dehydrogenase from Pseudomonas putida (gene mdlB), which catalyses the reduction of (S)-mandelate to benzoylformate.The first step in the reaction mechanism of these enzymes is the abstraction of the proton from the α-carbon of the substrate producing a carbanion which can subsequently attach to the N5 atom of FMN. A conserved histidine has been shown [
] to be involved in the removal of the proton. The region around this active site residue is highly conserved and contains an arginine residue which is involved in substrate binding.
FMN-dependent alpha-hydroxy acid dehydrogenase, active site
Type:
Active_site
Description:
A number of oxidoreductases that act on alpha-hydroxy acids and which are FMN-containing flavoproteins have been shown [
,
,
] to be structurally related.The first step in the reaction mechanism of these enzymes is the abstraction of the proton from the α-carbon of the substrate producing a carbanion which can subsequently attach to the N5 atom of FMN. A conserved histidine has been shown [
] to be involved in the removal of the proton. The region around this active site residue is highly conserved and contains an arginine residue which is involved in substrate binding.
This group represents alpha-hydroxy acid FMN-dependent dehydrogenases, including human glycolate oxidase (GO), L-lactate oxidase (LOX) [
] and bacterial L-lactate dehydrogenase. GO catalyses the FMN-dependent oxidation of glycolate to glyoxylate and glyoxylate to oxalate. The latter is a key metabolite in kidney stone formation. 4-carboxy-5-dodecylsulphanyl-1,2,3-triazole (CDST) is an inhibitor of this enzyme. In contrast to most alpha-hydroxy acid oxidases, including spinach glycolate oxidase, a loop region, known as loop 4, is completely visible when the GO active site contains a small ligand. Since this is an unique structural feature, it has the potential to be a target for drugs to decrease glycolate and glyoxylate levels in primary hyperoxaluria type 1 patients who have the inability to convert peroxisomal glyoxylate to glycine [].This entry also includes the fungal protein FUB9 by virtue of sequence similarity to the FMN-dependent alpha-hydroxy acid dehydrogenase family. FUB9 is an oxidase that is part of the gene cluster that mediates the biosynthesis of fusaric acid [
].
The Lsm14 N-terminal domain is a type of LSM domain found in Lsm14 proteins (also known as Rap55) [
,
] and in the Saccharomyces cerevisiae homologue Scd6 []. The domain is also found in the human EDC3 protein (enhancer of mRNA-decapping protein 3) where it is fused to the the Rossmanoid YjeF-N domain []. In addition, both EDC3 and Scd6 are found fused to the FDF domain [,
].
The FDF domain, so called because of the conserved FDF at its N termini, is an entirely α-helical domain with multiple exposed hydrophilic loops [
]. It is found at the C terminus of Scd6p-like SM domains [,
]. It is also found with other divergent Sm domains and in proteins such as Dcp3p and FLJ21128, where it is found N-terminal to the YjeF-N domain, a novel Rossmann fold domain [].
Sm and Sm-like proteins of the RNA-binding Lsm (like Sm) domain family are found in all domains of life and are generally involved in important RNA-
processing tasks. Lsm13-16 homologues share a domain organisation consisting of a divergent N-terminal Lsm domain and a central or C-terminal consensus motif DFDF-x(7)-F. In few other sequences, the DFDF box is replaced by a DYDF or EFDF box [,
].The FFD box and TFG box are two other strongly conserved sequence motifs(Y-x-K-x(3)-FFD-x-[IL]-S and [RKH]-x(2,5)-E-x(0-2)-[RK]-x(3,4)-[DE]-TFG respectively) contained in Lsm13-15, but not Lsm16, homologues. They succeed the DFDF-x(7)-F motif and are also predicted to be of helical nature [
].This entry represents the TGF box.
This is a family of microtubule associated proteins, including MAP65 (MAP65-1/2/3/4/5/6/7/8/9) from Arabidopsis, Ase1 from yeast, and PRC1 from mammals.Ase1 is required for spindle elongation and stabilisation. It is cell cycle-regulated by anaphase promoting complex [
]. It is a potential Cdc28p substrate []. MAP65-1 plays a role in stabilising anti-parallel microtubules in the central spindle at anaphase to early cytokinesis. MAP65-1 is cell cycle regulated by phosphorylation [
,
,
,
,
].PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone [
]. It is a key regulator of cytokinesis that cross-links antiparallel microtubules at an average distance of 35 nM [,
]. PRC1 is also required for KIF14 (a kinesin-3 family motor protein) localisation to the central spindle and midbody [,
,
] and is required to recruit PLK1 to the spindle. It stimulates PLK1 phosphorylation of RACGAP1/HsCyk-4 to allow recruitment of ECT2 to the central spindle [].
Proteins synthesized on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. This traffic is bidirectional, to ensure that proteins required to form vesicles are recycled. Vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transfer [
]. Clathrin coats contain both clathrin and adaptor complexes that link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. The two major types of clathrin adaptor complexes are the heterotetrameric adaptor protein (AP) complexes, and the monomeric GGA (Golgi-localising, Gamma-adaptin ear domain homology, ARF-binding proteins) adaptors [
]. All AP complexes are heterotetramers composed of two large subunits (adaptins), a medium subunit (mu) and a small subunit (sigma). Each subunit has a specific function. Adaptin subunits recognise and bind to clathrin through their hinge region (clathrin box), and recruit accessory proteins that modulate AP function through their C-terminal appendage domains. By contrast, GGAs are monomers composed of four domains, which have functions similar to AP subunits: an N-terminal VHS (Vps27p/Hrs/Stam) domain, a GAT (GGA and Tom1) domain, a hinge region, and a C-terminal GAE (gamma-adaptin ear) domain. The GAE domain is similar to the AP gamma-adaptin ear domain, being responsible for the recruitment of accessory proteins that regulate clathrin-mediated endocytosis [].While clathrin mediates endocytic protein transport from ER to Golgi, coatomers (COPI, COPII) primarily mediate intra-Golgi transport, as well as the reverse Golgi to ER transport of dilysine-tagged proteins [
]. Coatomers reversibly associate with Golgi (non-clathrin-coated) vesicles to mediate protein transport and for budding from Golgi membranes []. Coatomer complexes are hetero-oligomers composed of at least an alpha, beta, beta', gamma, delta, epsilon and zeta subunits. This entry represents the N-terminal domain of various adaptins from different AP clathrin adaptor complexes (including AP1, AP2, AP3 and AP4), and from the beta and gamma subunits of various coatomer (COP) adaptors. This domain has a 2-layer alpha/alpha fold that forms a right-handed superhelix, and is a member of the ARM repeat superfamily [
]. The N-terminal region of the various AP adaptor proteins share strong sequence identity; by contrast, the C-terminal domains of different adaptins share similar structural folds, but have little sequence identity []. It has been proposed that the N-terminal domain interacts with another uniform component of the coated vesicles.
Adapter-like complex 4 (AP-4) is a heterotetramer composed of two large adaptins (epsilon-type subunit AP4E1 and beta-type subunit AP4B1), a medium adaptin (mu-type subunit AP4M1) and a small adaptin (sigma-type AP4S1). It is a subunit of a novel type of clathrin- or non-clathrin-associated protein coat involved in targeting proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system [
,
].This group represents an adaptor protein complex AP-4, epsilon subunit.
This family of plant methyltransferases contains enzymes that act on a variety of substrates including salicylic acid, jasmonic acid and 7-methylxanthine. Caffeine is synthesised through sequential three-step methylation of xanthine derivatives at positions 7-N, 3-N, and 1-N [
,
]. The protein 7-methylxanthine methyltransferase (designated as CaMXMT) catalyses the second step to produce theobromine [].
Cytochrome P450 enzymes are a superfamily of haem-containing mono-oxygenases that are found in all kingdoms of life, and which show extraordinary diversity in their reaction chemistry. In mammals, these proteins are found primarily in microsomes of hepatocytes and other cell types, where they oxidise steroids, fatty acids and xenobiotics, and are important for the detoxification and clearance of various compounds, as well as for hormone synthesis and breakdown, cholesterol synthesis and vitamin D metabolism. In plants, these proteins are important for the biosynthesis of several compounds such as hormones, defensive compounds and fatty acids. In bacteria, they are important for several metabolic processes, such as the biosynthesis of antibiotic erythromycin in Saccharopolyspora erythraea (Streptomyces erythraeus).Cytochrome P450 enzymes use haem to oxidise their substrates, using protons derived from NADH or NADPH to split the oxygen so a single atom can be added to a substrate. They also require electrons, which they receive from a variety of redox partners. In certain cases, cytochrome P450 can be fused to its redox partner to produce a bi-functional protein, such as with P450BM-3 from Bacillus megaterium [
], which has haem and flavin domains.Organisms produce many different cytochrome P450 enzymes (at least 58 in humans), which together with alternative splicing can provide a wide array of enzymes with different substrate and tissue specificities. Individual cytochrome P450 proteins follow the nomenclature: CYP, followed by a number (family), then a letter (subfamily), and another number (protein); e.g. CYP3A4 is the fourth protein in family 3, subfamily A. In general, family members should share >40% identity, while subfamily members should share >55% identity.Cytochrome P450 proteins can also be grouped by two different schemes. One scheme was based on a taxonomic split: class I (prokaryotic/mitochondrial) and class II (eukaryotic microsomes). The other scheme was based on the number of components in the system: class B (3-components) and class E (2-components). These classes merge to a certain degree. Most prokaryotes and mitochondria (and fungal CYP55) have 3-component systems (class I/class B) - a FAD-containing flavoprotein (NAD(P)H-dependent reductase), an iron-sulphur protein and P450. Most eukaryotic microsomes have 2-component systems (class II/class E) - NADPH:P450 reductase (FAD and FMN-containing flavoprotein) and P450. There are exceptions to this scheme, such as 1-component systems that resemble class E enzymes [
,
,
]. The class E enzymes can be further subdivided into five sequence clusters, groups I-V, each of which may contain more than one cytochrome P450 family (eg, CYP1 and CYP2 are both found in group I). The divergence of the cytochrome P450 superfamily into B- and E-classes, and further divergence into stable clusters within the E-class, appears to be very ancient, occurring before the appearance of eukaryotes.This entry represents a conserved site based around a highly conserved cysteine residue involved in binding haem iron in the fifth coordination site, which is found in the C-terminal regions of P450 proteins.
This entry represents the N-terminal domain found in several lipid-binding serum glycoproteins. The N- and C-terminal domains share a similar two-layer alpha/beta structure, but they show little sequence identity. Proteins containing this N-terminal domain include:Bactericidal permeability-increasing protein (BPI)Lipopolysaccharide-binding protein (LBP)Cholesteryl ester transfer protein (CETP)Phospholipid transfer protein (PLTP)Palate, lung and nasal epithelium carcinoma-associated protein (PLUNC)Bactericidal permeability-increasing protein (BPI) is a potent antimicrobial protein of 456 residues that binds to and neutralises lipopolysaccharides from the outer membrane of Gram-negative bacteria [
]. BPI contains two domains that adopt the same structural fold, even though they have little sequence similarity []. Lipopolysaccharide-binding protein (LBP) is an endotoxin-binding protein that is closely related to, and functions in a co-ordinated manner with BPI to facilitate an integrated host response to invading Gram-negative bacteria [
].Cholesteryl ester transfer protein (CETP) is a glycoprotein that facilitates the transfer of lipids (cholesteryl esters and triglycerides) between the different lipoproteins that transport them through plasma, including HDL, LDL, VLDL and chylomicrons. These lipoproteins shield the lipids from water by encapsulating them within a coating of polar lipids and proteins [
].Phospholipid transfer protein (PLTP) exchanges phospholipids between lipoproteins and remodels high-density lipoproteins (HDLs) [
].Palate, lung and nasal epithelium carcinoma-associated protein (PLUNC) is a potential host defensive protein that is secreted from the submucosal gland to the saliva and nasal lavage fluid. PLUNC appears to be a secreted product of neutrophil granules that participates in an aspect of the inflammatory response that contributes to host defence [
]. Short palate, lung and nasal epithelium clone 1 (SPLUNC1) may bind the lipopolysaccharide of Gram-negative nanobacteria, thereby playing an important role in the host defence of nasopharyngeal epithelium [].
This entry represents the C-terminal domain found in several lipid-binding serum glycoproteins. The N- and C-terminal domains share a similar two-layer alpha/beta structure, but they show little sequence identity. Proteins containing this C-terminal domain include:Bactericidal permeability-increasing protein (BPI)Lipopolysaccharide-binding protein (LBP)Cholesteryl ester transfer protein (CETP)Phospholipid transfer protein (PLTP)Palate, lung and nasal epithelium carcinoma-associated protein (PLUNC)Bactericidal permeability-increasing protein (BPI) is a potent antimicrobial protein of 456 residues that binds to and neutralises lipopolysaccharides from the outer membrane of Gram-negative bacteria [
]. BPI contains two domains that adopt the same structural fold, even though they have little sequence similarity []. Lipopolysaccharide-binding protein (LBP) is an endotoxin-binding protein that is closely related to, and functions in a co-ordinated manner with BPI to facilitate an integrated host response to invading Gram-negative bacteria [
].Cholesteryl ester transfer protein (CETP) is a glycoprotein that facilitates the transfer of lipids (cholesteryl esters and triglycerides) between the different lipoproteins that transport them through plasma, including HDL, LDL, VLDL and chylomicrons. These lipoproteins shield the lipids from water by encapsulating them within a coating of polar lipids and proteins [
].Phospholipid transfer protein (PLTP) exchanges phospholipids between lipoproteins and remodels high-density lipoproteins (HDLs) [
].Palate, lung and nasal epithelium carcinoma-associated protein (PLUNC) is a potential host defensive protein that is secreted from the submucosal gland to the saliva and nasal lavage fluid. PLUNC aapears to be a secreted product of neutrophil granules that participates in an aspect of the inflammatory response that contributes to host defence [
]. Short palate, lung and nasal epithelium clone 1 (SPLUNC1) may bind the lipopolysaccharide of Gram-negative nanobacteria, thereby playing an important role in the host defence of nasopharyngeal epithelium [].
This superfamily represents a structural domain with a core structure consisting of two layers, alpha/beta. These homologous structural domains can show little sequence identity with each other. A number of mammalian lipid-binding serum glycoproteins contain one or more such structural domains, including:Bactericidal permeability-increasing protein (BPI)Lipopolysaccharide-binding protein (LBP)Cholesteryl ester transfer protein (CETP)Phospholipid transfer protein (PLTP)Palate, lung and nasal epithelium carcinoma-associated protein (PLUNC)Bactericidal permeability-increasing protein (BPI) is a potent antimicrobial protein of 456 residues that binds to and neutralises lipopolysaccharides from the outer membrane of Gram-negative bacteria [
]. BPI contains two domains that adopt the same structural fold, even though they have little sequence similarity []. Lipopolysaccharide-binding protein (LBP) is an endotoxin-binding protein that is closely related to, and functions in a co-ordinated manner with BPI to facilitate an integrated host response to invading Gram-negative bacteria [
].Cholesteryl ester transfer protein (CETP) is a glycoprotein that facilitates the transfer of lipids (cholesteryl esters and triglycerides) between the different lipoproteins that transport them through plasma, including HDL, LDL, VLDL and chylomicrons. These lipoproteins shield the lipids from water by encapsulating them within a coating of polar lipids and proteins [
].Phospholipid transfer protein (PLTP) exchanges phospholipids between lipoproteins and remodels high-density lipoproteins (HDLs) [
].Palate, lung and nasal epithelium carcinoma-associated protein (PLUNC) is a potential host defensive protein that is secreted from the submucosal gland to the saliva and nasal lavage fluid. PLUNC appears to be a secreted product of neutrophil granules that participates in an aspect of the inflammatory response that contributes to host defence [
]. Short palate, lung and nasal epithelium clone 1 (SPLUNC1) may bind the lipopolysaccharide of Gram-negative nanobacteria, thereby playing an important role in the host defence of nasopharyngeal epithelium [].
This conserved hypothetical protein family with four predicted transmembrane regions is found in
Escherichia coli, Haemophilus influenzae, and Helicobacter pylori 26695, among completed genomes.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Sec20 is a membrane glycoprotein and a SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) involved in retrograde transport from the Golgi to the endoplasmic reticulum (ER) [
]. It is also required for N- and O-glycosylation in the Golgi [].
This is the C-terminal domain of the TAF6 subunit of the general transcription factor TFIID. The crystal structure reveals the presence of five conserved HEAT repeats. This region is necessary for the complexing together of the subunits TAF5, TAF6 and TAF9 [
,
].
TATA box binding protein associated factor (TAF), histone-like fold domain
Type:
Domain
Description:
The TATA box binding protein associated factor (TAF) is part of the transcription initiation factor TFIID multimeric protein complex. TFIID plays a central role in mediating promoter responses to various activators and repressors. It binds tightly to TAFII-250 and directly interacts with TAFII-40. TFIID is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFS). TAF proteins adopt a histone-like fold [
,
].The DNA-binding general transcription factor complex TFIID is central to the initiation of DNA-dependent RNA polymerase II transcription. TFIID is the only general transcription initiation factor that bind to the TATA box. The binding of TFIID to the TATA-box is the first step in the formation of a complex able to initiate transcription [
]. TFIID consists of the TATA binding protein (TBP) and 14 TBP-associated factors (TAFs). One copy of each TAF1, TAF2, TAF3, TAF7, TAF8, TAF11, TAF13, two copies of each TAF4, TAF5, TAF6, TAF9, TAF10, TAF12, and three copies of TAF14 [].
The glucose-methanol-choline (GMC) oxidoreductases are FAD flavoproteins oxidoreductases [
,
].These enzymes include a variety of proteins, including choline dehydrogenase (CHD), methanol oxidase (MOX) and cellobiose dehydrogenase (
) [
] which share a number of regions of sequence similarities. One of these regions, located in the N-terminal section, corresponds to the FAD ADP-binding domain. The function of the other conserved domains is not yet known.
The long-chain alcohol oxidase (FAO) acts as the second enzyme in the omega-oxidation pathway of lipid degradation in yeast [
,
]. Four homologues have been described in Arabidopsis thaliana: AtFAO1, AtFAO3, AtAFO4a, and AtFAO4b [].
The glucose-methanol-choline (GMC) oxidoreductases are FAD flavoproteins oxidoreductases [
,
]. These enzymes include a variety of proteins; choline dehydrogenase (CHD), methanol oxidase (MOX) and cellobiose dehydrogenase () [
] which share a number of regions of sequence similarities. The function of this C-terminal conserved domain is not yet known.
This entry represents a group of proteins from Streptophytes, including Protein VASCULATURE COMPLEXITY AND CONNECTIVITY (also known as DEAL1), Protein DESIGUAL 2-4 (DEAL2-4) and Protein MODIFYING WALL LIGNIN-1/2 (MWL-1/2). DEAL1 is required for embryo provasculature development and cotyledon vascular complexity and connectivity [
,
]. DEAL2 and 3 ensure bilateral symmetry development and early leaf margin patterning, probably via the regulation of auxin and CUC2 distribution []. MWL1 and 2 are involved in secondary cell wall biology, specifically lignin biosynthesis []. Proteins included in this family contain a number of conserved cysteine residues.
In bacteria, FtsZ [
,
,
,
] is an essential cell division protein involved in the initiation of this event. It assembles into a cytokinetic ring on the inner surface of the cytoplasmic membrane at the place where division will occur. The ring serves as a scaffold that is disassembled when septation is completed. FtsZ ring formation is initiated at a single site on one side of the bacterium and appears to grow bidirectionally. In Escherichia coli, MinCD , encoded by the MinB locus, form a complex which appears to block the formation of FtsZ rings at the cell poles, at the ancient mid cell division sites, whilst MinE, encoded at the same locus, specifically prevents the action of MinCD at mid cell.
FtsZ is a GTP binding protein with a GTPase activity. It undergoes GTP-dependent polymerisation into filaments (or tubules) that seem to form a cytoskeleton involved in septum synthesis. The structure and the properties of FtsZ clearly provide it with the capacity for the cytoskeletal, perhaps motor role, necessary for "contraction"along the division plane. In addition, however, the FtsZ ring structure provides the framework for the recruitment or assembly of the ten or so membrane and cytoplasmic proteins, uniquely required for cell division in E. coli or Bacillus subtilis, some of which are required for biogenesis of the new hemispherical poles of the two daughter cells. FtsZ can polymerise into various structures, for example a single linear polymer of FtsZ monomers, called a protofilament. Protofilaments can associate laterally to form pairs (sometimes called thick filaments), bundles (ill-defined linear associations of multiple protofilaments) or thick filaments, sheets (parallel or anti-parallel two-dimensional associations of thick filaments) and tubes (anti-parallel associations of thick filaments in a circular fashion to form a tubular structure). In addition, small circles of FtsZ monomers (a short protofilament bent around to join itself, apparently head to tail) have been observed and termed mini-rings. FtsZ is a protein of about 400 residues which is well conserved across bacterial species and which is also present in the chloroplast of plants [
] as well as in archaebacteria []. FtsZ is a homologue of eukaryotic tubulin with which it shows structural similarity.
In bacteria, FtsZ [
,
,
,
] is an essential cell division protein involved in the initiation of this event. It assembles into a cytokinetic ring on the inner surface of the cytoplasmic membrane at the place where division will occur. The ring serves as a scaffold that is disassembled when septation is completed. FtsZ ring formation is initiated at a single site on one side of the bacterium and appears to grow bidirectionally. In Escherichia coli, MinCD , encoded by the MinB locus, form a complex which appears to block the formation of FtsZ rings at the cell poles, at the ancient mid cell division sites, whilst MinE, encoded at the same locus, specifically prevents the action of MinCD at mid cell.
FtsZ is a GTP binding protein with a GTPase activity. It undergoes GTP-dependent polymerisation into filaments (or tubules) that seem to form a cytoskeleton involved in septum synthesis. The structure and the properties of FtsZ clearly provide it with the capacity for the cytoskeletal, perhaps motor role, necessary for "contraction"along the division plane. In addition, however, the FtsZ ring structure provides the framework for the recruitment or assembly of the ten or so membrane and cytoplasmic proteins, uniquely required for cell division in E. coli or Bacillus subtilis, some of which are required for biogenesis of the new hemispherical poles of the two daughter cells. FtsZ can polymerise into various structures, for example a single linear polymer of FtsZ monomers, called a protofilament. Protofilaments can associate laterally to form pairs (sometimes called thick filaments), bundles (ill-defined linear associations of multiple protofilaments) or thick filaments, sheets (parallel or anti-parallel two-dimensional associations of thick filaments) and tubes (anti-parallel associations of thick filaments in a circular fashion to form a tubular structure). In addition, small circles of FtsZ monomers (a short protofilament bent around to join itself, apparently head to tail) have been observed and termed mini-rings. FtsZ is a protein of about 400 residues which is well conserved across bacterial species and which is also present in the chloroplast of plants [
] as well as in archaebacteria []. FtsZ is a homologue of eukaryotic tubulin with which it shows structural similarity.
The FtsZ family of proteins are involved in polymer formation. FtsZ is the polymer-forming protein of bacterial cell division. It is part of a ring in the middle of the dividing cell that is required for constriction of cell membrane and cell envelope to yield two daughter cells. FtsZ is a GTPase, like tubulin [
]. FtsZ can polymerise into tubes, sheets, and rings in vitro and is ubiquitous in eubacteria and archaea [].This entry represents a domain of FtsZ. In most FtsZ proteins is found in the C terminus, except in some alphaproteobacteria proteins where there is an extension C-terminal domain
.
Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP. There are several different types of transmembrane ATPases, which can differ in function (ATP hydrolysis and/or synthesis), structure (e.g., F-, V- and A-ATPases, which contain rotary motors) and in the type of ions they transport [
,
]. The different types include:F-ATPases (ATP synthases, F1F0-ATPases), which are found in mitochondria, chloroplasts and bacterial plasma membranes where they are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).V-ATPases (V1V0-ATPases), which are primarily found in eukaryotes and they function as proton pumps that acidify intracellular compartments and, in some cases, transport protons across the plasma membrane [
]. They are also found in bacteria [].A-ATPases (A1A0-ATPases), which are found in Archaea and function like F-ATPases, though with respect to their structure and some inhibitor responses, A-ATPases are more closely related to the V-ATPases [
,
].P-ATPases (E1E2-ATPases), which are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.E-ATPases, which are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.V-ATPases (also known as V1V0-ATPase or vacuolar ATPase) are found in the eukaryotic endomembrane system, and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, and are involved in a variety of vital intra- and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release [
]. V-ATPases are composed of two linked complexes: the V1 complex (subunits A-H) contains the catalytic core that hydrolyses ATP, while the V0 complex (subunits a, c, c', c'', d) forms the membrane-spanning pore. V-ATPases may have an additional role in membrane fusion through binding to t-SNARE proteins [].This entry represents subunit e (or subunit M9.2) found in the V0 complex of certain V-ATPases. The V0 complex contains subunit c (proton-conducting pore), as well as accessory subunits that function in assembly, targeting or regulation of the V-ATPase complex. Subunit e is an extremely hydrophobic protein of approximately 9kDa, which may be required for assembly of vacuolar ATPases [
]. The amino terminal domain of subunit E interacts with the H subunit and is required fo V-ATPase function []. Different isoforms of this subunit exist sometimes annotated as e1 and e2 also a neuron-specific isoform, NM9.2 has been identified [].
Late embryogenesis abundant protein, LEA_2 subgroup
Type:
Domain
Description:
LEA (late embryogenesis abundant) proteins were first identified in land plants. Plant LEA proteins have been found to accumulate to high levels during the last stage of seed formation (when a natural desiccation of the seed tissues takes place) and during periods of water deficit in vegetative organs. Later, LEA homologues have also been found in various species [
,
]. They have been classified into several subgroups in Pfam and according to Bray and Dure [].This entry represents Pfam LEA_2, or LEA14 (D-95) from Dure. The structure of Arabidopsis LEA14 has been revealed [
].
50S ribosomal protein L18Ae/60S ribosomal protein L20 and L18a
Type:
Family
Description:
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 [
,
].This entry represent the 50S ribosomal protein L18Ae from archaea and 60S ribosomal protein L20/L18a from eukaryotes.
This entry includes the eukaryotic 60S ribosomal protein L18ae [
] the archaea 50S ribosomal protein LX and higher eukaryote 60S ribosomal protein L18A. Rat ribosomal protein L18 is homologous to Xenopus laevis L14 [].
This family represents a group of proteins including E3 ubiquitin-protein ligases related to BOI (Botrytis Susceptible1 Interactor), which is involved in the regulation of pathogen and abiotic stress responses [
]. This entry also includes some uncharacterised RING finger proteins.
The HEAT repeat is a tandemly repeated, 37-47 amino acid long module occurring in a number of cytoplasmic proteins, including the four name-giving proteins huntingtin, elongation factor 3 (EF3), the 65 kDa alpha regulatory subunit of protein phosphatase 2A (PP2A) and the yeast PI3-kinase TOR1 [
]. Arrays of HEAT repeats consists of 3 to 36 units forming a rod-like helical structure and appear to function as protein-protein interaction surfaces. It has been noted that many HEAT repeat-containing proteins are involved in intracellular transport processes.In the crystal structure of PP2A PR65/A [
], the HEAT repeats consist of pairs of antiparallel α-helices [].
This superfamily represents a domain with a distorted supersandwich structure consisting of 18 strands in two sheets, which probably functions to bind carbohydrates in enzymes that act on sugars. Domains with this structure occur in several protein families, including galactose mutarotase (
); domain 5 of beta-galactosidase (
); the central domain of hyaluronate lyase-like enzymes, such as chondroitinase AC (
), chrondroitin ABC lyase I, and hyaluronate lyase (
) itself [
]; and the N-terminal domain of bacterial glucoamylase () [
] and rhamnogalacturonate lyase ().
This entry represents the EndoU domain found at the C-terminal of EndoU endoribonucleases, which carries out a conserved RNA processing function. The EndoU domain cleaves RNA at uridylates and release 2',3'-cyclic phosphodiester ends. The EndoU domain is an α/β domain, that contains nine α-helices and three antiparallel β-sheets; the latter are clustered on one side of the domain, whereas the α-helices are largely on the other side [
]. It contains a conserved trio of catalytic residues, two histidines and a lysine.EndoU is a family of metal-dependent endoribonucleases that is broadly conserved among eukaryotes [
,
]. EndoU family members have RNA-binding and endoribonuclease activities and appear to be involved in many aspects of
biology, including small nucleolar RNA biogenesis, endoplasmic reticulum (ER) network formation, immune response, and neurodegeneration:Xenopus laevis endoribonuclease XendoU is responsible for processing the intron encoded U16 and U86 small nucleolar RNAs (snoRNAs) [
,
,
].Human EndoU, also known as PP11 (placental protein 11), has an endoribonuclease activity with placental tissue specificity [
,
,
].Drosophila melanogaster CG2145 and DendoU endoribonucleases [
].Caenorhabditis elegans endu-2 regulates nucleotide metabolism and germ cell proliferation in response to nucleotide imbalance and other genotoxic stress [
].
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.Family 14 (
,
) encompasses the beta-amylase enzymes.
Beta-amylases, which are found in plants and bacteria, hydrolyse 1,4-alpha-glucosidic linkages in starch-type polysaccharide substrates, removingsuccessive maltose units from the non-reducing ends of the chains. In Solanum tuberosum (potato), the enzyme has been found to work optimally at 40 degrees C,
becoming unstable above this temperature. On the basis of sequencecomparisons, plant and bacterial beta-amylases can be readily distinguished
from each other.The 3D structure of a complex of soybean beta-amylase with an inhibitor
(alpha-cyclodextrin) has been determined to 3.0A resolution by X-raydiffraction [
]. The enzyme folds into large and small domains: the largedomain has a (beta alpha)8 super-secondary structural core, while the smaller
is formed from two long loops extending from the beta-3 and beta-4 strandsof the (beta alpha)8 fold [
]. The interface of the two domains, togetherwith shorter loops from the (beta alpha)8 core, form a deep cleft, in which
the inhibitor binds []. Two maltose molecules also bind in the cleft,one sharing a binding site with alpha-cyclodextrin, and the other sitting
more deeply in the cleft [].
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.Glycoside hydrolase family 14
comprises enzymes with only one known activity; beta-amylase (). A Glu residue has been proposed as a catalytic residue, but it is not known if it is the nucleophile or the proton donor.
Beta-amylase [
,
] is an enzyme that hydrolyses 1,4-alpha-glucosidic linkages in starch-type polysaccharide substrates so as to removesuccessive maltose units from the non-reducing ends of the chains. Beta-amylase is present in certain bacteria as well as in plants.
The 3D structure of a complex of soybean beta-amylase with an inhibitor
(alpha-cyclodextrin) has been determined to 3.0A resolution by X-raydiffraction [
]. The enzyme folds into large and small domains: the largedomain has a (beta alpha)8 super-secondary structural core, while the smaller
is formed from two long loops extending from the beta-3 and beta-4 strandsof the (beta alpha)8 fold [
]. The interface of the two domains, togetherwith shorter loops from the (beta alpha)8 core, form a deep cleft, in which
the inhibitor binds []. Two maltose molecules also bind in the cleft,one sharing a binding site with alpha-cyclodextrin, and the other sitting
more deeply in the cleft [].This entry represents two highly conserved sequence regions found in all known beta-amylases. The first of these regions (BETA_AMYLASE_1) is located in the N-terminal section of the enzymes and contains an aspartate which is known [
] to be involved in the catalytic mechanism. The second (BETA_AMYLASE_2), located in a more central location, is centred around a glutamate which is also involved [] in the catalytic mechanism.
The GTD-binding domain is a plant-specific protein-protein interaction domain.
It emerged in primitive land plants and founded a multigene family that isconserved in all flowering plants. Proteins with GTD-binding domains fall into
four groups, where group 1-3 contain the GTD-binding domain at the C-terminalhalf of the protein and one (group 2) or more (group1) predicted transmembrane
domains, or an endoplasmic reticulum signal peptide (group 3) at the N-terminus, whereas group 4 contains the GTD-binding domain near the N terminus.
GTD-binding domain proteins may constitute a family of myosin receptors, whichare associated with the surface of specific plant organelles, bind to the
globular tail domain (GTD) of myosin motor proteins, and thereby promoteactin-dependent organelle motility. It seems likely that myosin binding is a
common property of the GTD-binding domain, whereas the ability of FLOURY1 tobind maize-specific zeins is a specific feature of this endoplasmic reticulum
(ER)-associated protein.The GTD-binding domain is predicted to adopt a coiled-coil structure.Some proteins known to contain a GTD-binding domain are listed below:Maize FLOURY1 (FL1), which belongs to group 1. Its GTD-binding domain
facilitates the localization of 22kDa alpha-zein [].Arabidopsis myosin binding (MyoB) proteins 1-6 and 7, which belong
respectively to group 3 and 4. They bind to myosin XI [].Tobacco RAC5 interacting subapical pollen tube protein (RISAP), which
belongs to group 3. It binds via its GTD-binding domain to the GTD domainof a pollen tube myosin XI [
].Lily LLP13, which belongs to group 3. It is likely a cytoskeleton-binding
protein that binds with intermediate filaments (IFs) that potentially existin pollen tubes [
].
NAD(P)H-quinone oxidoreductase subunit L (NdhL) is a component of the NDH-1L complex that is one of the proton-pumping NADH:ubiquinone oxidoreductases that catalyse the electron transfer from NADH to ubiquinone linked with proton translocation across the membrane. NDH-1L is essential for photoheterotrophic cell growth. NdhL appears to contain two transmembrane helices and it is necessary for the functioning of though not the correct assembly of the NDH-1 complex in Synechocystis 6803. The conservation between cyanobacteria and green plants suggests that chloroplast NDH-1 complexes contain related subunits [
].
TMEM214 is a critical mediator, in cooperation with CASP4, of endoplasmic reticulum-stress induced apoptosis. It is required or the activation of CASP4 following endoplasmic reticulum stress [
].
Poly(ADP-ribose) polymerases (PARP) are a family of enzymes
present in eukaryotes, which catalyze the poly(ADP-ribosyl)ation of a limitednumber of proteins involved in chromatin architecture, DNA repair, or in DNA
metabolism, including PARP itself. PARP, also known as poly(ADP-ribose)synthetase and poly(ADP-ribose) transferase, transfers the ADP-ribose moiety
from its substrate, nicotinamide adenine dinucleotide (NAD), to carboxylategroups of aspartic and glutamic residues. Whereas some PARPs might function in
genome protection, others appear to play different roles in the cell,including telomere replication and cellular transport. PARP-1 is a
multifunctional enzyme. The polypeptide has a highly conserved modularorganisation consisting of an N-terminal DNA-binding domain, a central
regulating segment, and a C-terminal or F region accommodating the catalyticcentre. The F region is composed of two parts: a purely α-helical N-
terminal domain (alpha-hd), and the mixed alpha/beta C-terminal catalyticdomain bearing the putative NAD binding site. Although proteins of the PARP
family are related through their PARP catalytic domain, they do not resembleeach other outside of that region, but rather, they contain unique domains
that distinguish them from each other and hint at their discrete functions.Domains with which the PARP catalytic domain is found associated include
zinc fingers, SAP, ankyrin, BRCT, Macro, SAM, WWE and UIM domains [,
,
].The alpha-hd domain is about 130 amino acids in length and consists of an up-up-down-up-down-down motif of helices. It is
thought to relay the activation signal issued on binding to damaged DNA [,
].The PARP catalytic domain is about 230 residues in length. Its core consists of a five-stranded antiparallel β-sheet and
four-stranded mixed β-sheet. The two sheets are consecutive and areconnected via a single pair of hydrogen bonds between two strands that run at
an angle of 90 degrees. These central β-sheets are surrounded by five α-helices, three 3(10)-helices, and by a three- and a two-stranded β-sheet ina 37-residue excursion between two central β-strands [
,
]. The activesite, known as the 'PARP signature' is formed by a block of 50 amino acids
that is strictly conserved among the vertebrates andhighly conserved among all species. The 'PARP signature' is characteristic of
all PARP protein family members. It is formed by a segment of conserved aminoacid residues formed by a β-sheet, an α-helix, a 3(10)-helix, a β-sheet, and an α-helix [
].
This superfamily represents a structural domain with an α-β(4)-α(3) core fold. Domains of this structure are found in:Ubiquitin conjugating enzyme E2, as well as related proteins such as ubiquitin carrier protein 4 and ubiquitin-protein ligase W [
].The UEV domain in tumour susceptibility gene 101 [
] and vacuolar protein sorting-associated protein [].RWD domain, found in RING finger and WD repeat-containing proteins, such as EIF-2 kinase 4 (GCN2-like protein) [
].UFC1-like domain found in Ufm1-conjugating enzyme 1 [
].
Ubiquitin-conjugating enzymes (UBC or E2 enzymes) (
) [
,
,
]
catalyse the covalent attachment of ubiquitin to target proteins. Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1, ), a ubiquitin-conjugating enzyme (E2), and a ubiquitin ligase (E3,
,
), which work sequentially in a cascade [
]. The E1 enzyme mediates an ATP-dependent transfer of a thioester-linked ubiquitin molecule to a cysteine residue on the E2 enzyme. The E2 enzyme then either transfers the ubiquitin moiety directly to a substrate, or to an E3 ligase, which can also ubiquitinylate a substrate.There are several different E2 enzymes (over 30 in humans), which are broadly grouped into four classes, all of which have a core catalytic domain (containing the active site cysteine), and some of which have short N- and C-terminal amino acid extensions: class I enzymes consist of just the catalytic core domain (UBC), class II possess a UBC and a C-terminal extension, class III possess a UBC and an N-terminal extension, and class IV possess a UBC and both N- and C-terminal extensions. These extensions appear to be important for some subfamily function, including E2 localisation and protein-protein interactions [
]. In addition, there are proteins with an E2-like fold that are devoid of catalytic activity (such as protein crossbronx from flies), but which appear to assist in poly-ubiquitin chain formation.
Serine palmitoyltransferase (SPT) catalyzes the first committed step in sphingolipid biosynthesis.
In mammals, two small subunits of serine palmitoyltransferase, ssSPTa and ssSPTb, substantially enhance the activity of SPT, conferring full enzyme activity upon it []. The 2 ssSPT isoforms share a conserved hydrophobic central domain, which is predicted to reside in the membrane.This entry represents the small subunits of serine palmitoyltransferase. It also includes a number of putative uncharacterised proteins from fungi and plants.
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [
,
,
,
,
]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. The RING finger is a well characterised zinc finger which coordinates two zinc atoms in a cross-braced manner (see
). According to the pattern of cysteines and histidines three different subfamilies of RING finger can be defined. The classical RING finger (RING-HC) has a histidine at the fourth coordinating position and a cysteine at the fifth. In the RING-H2 variant, both the fourth and fifth positions are occupied by histidines. The RING-CH, which is very similar to the classical RING finger, differs from both of these variants in that it has a cys residue in the fourth position and a His in the fifth. Another difference between the RING-CH and the common RING variants is a somewhat longer peptide segment between the fourth and fifth zinc-coordinating residues. The RING-CH zinc finger has thus the same arrangement of cysteine and histidine (C4HC3) as the PHD zinc finger (see
) but it contains features (spacing between the cysteines and the histidine) characteristic of the genuine RING-finger (C3HC4) [
,
]. The RING-CH-type is an E3 ligase mainly found in proteins associated to membranes [,
].The solution structure of the RING-CH-type zinc finger of the herpesvirus Mir1 protein has shown that it is an outlying relative of the cellular RING finger domain family, with its polypeptide backbone much more closely resembling that of RING domains than PHD domains [
]. The only real difference between the classic and variant RING domains, other than the alteration of zinc ligands, is theloss of the small β-sheet found in RING domains and the replacement of one strand of this sheet with a single turn of helix. Some proteins that contains a RING-CH-type zinc finger are listed below:
Yeast Doa10/SSM4 (
). An E3 ligase essential for the endoplasmic reticulum associated degradation (ERAD), an ubiquitin-proteasome system responsible for the degradation of membrane and lumenal proteins of the endoplasmic reticulum.
Mammalian membrane-associated RING-CH 1 to 9 (MARCH1 to 9) proteins.Human herpesvirus 8 (HHV-8) (Kaposi's sarcoma-associated herpesvirus) modulator of immune recognition 1 (
). An E3 ubiquitin-protein ligase which promotes ubiquitination and subsequent degradation of host MHC-I and CD1D molecules, presumably to prevent lysis of infected cells by cytotoxic T-lymphocytes.
This entry represents the C-terminal domain of the endoplasmic reticulum vesicle transporter proteins. Proteins included in this entry are conserved from plants and fungi to humans. Erv46 (ERGIC3) works in close conjunction with Erv41 (ERGIC2) and together they form a complex which cycles between the endoplasmic reticulum and Golgi complex. Erv46-41 interacts strongly with the endoplasmic reticulum glucosidase II. Mammalian glucosidase II comprises a catalytic alpha-subunit and a 58kDa beta subunit, which is required for ER localisation. All proteins identified biochemically as Erv41p-Erv46p interactors are localised to the early secretory pathway and are involved in protein maturation and processing in the ER and/or sorting into COPII vesicles for transport to the Golgi [
].Proteins containing this domain also include disulfide isomerase (PDI)-C subfamily members from Arabidopsis. They are chimeric proteins containing the thioredoxin (Trx) domain of PDIs, and the conserved N- and C-terminal domains of Erv cargo receptors [
].
The conserved oligomeric Golgi (COG) complex is an eight-subunit (Cog1-8) peripheral Golgi protein involved in membrane trafficking and glycoconjugate synthesis [
]. COG7 is required for normal Golgi morphology and trafficking. Defects in COG7 are the cause of congenital disorder of glycosylation type 2E (CDG2E). CDGs are a family of severe inherited diseases caused by a defect in protein N-glycosylation [].
This family consists of several Luc7 protein homologues that are restricted to eukaryotes. In budding yeast, Luc7 is an essential subunit of the yeast U1 snRNP, which forms the spliceosomal commitment complex with other proteins that targets pre-mRNA to the splicing pathway [
,
]. Its N-terminal zinc finger has been found to bind pre-mRNA []. This entry also contains human and mouse Luc7 like (LUC7L) proteins [].
