Class V myosins are well studied unconventional myosins, represented by three paralogues (Myo5a, b, c) in vertebrates. Their C-terminal cargo binding domains (CBDs) are important for the binding of a diverse set of cargos, including membrane vesicles, organelles, proteins and mRNA [, , ]. They interact with several adaptor proteins, in case of Myo5b-CBD, Rab11-family interacting protein 2 [].
Members of this superfamily consist of a β-sheet region followed by an α-helix and an unstructured C terminus. The β-sheet region contains a CXCX...XCXC sequence with Cys residues located in two proximal loops and pointing towards each other. This precise function of this set of bacterial proteins is, as yet, unknown [].
Anthranilate (2-aminobenzoate) is an intermediate of tryptophan (Trp) biosynthesis and degradation. Members of this family are the small subunit of anthranilate 1,2-dioxygenase, which acts in Trp degradation by converting anthranilate to catechol. Closely related paralogs typically are the benzoate 1,2-dioxygenase small subunit, among the larger set of ring-hydroxylating dioxygenases [].
This family of proteins have no known function. There are two conserved sequence motifs: PEERWWL and GWR. This family is found in a very sporadic set of bacterial species, suggesting that it may have been horizontally transferred. One protein () is annotated as occurring on a plasmid.
This entry represents a set of E3 ubiquitin-protein ligases which accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates, like SMURF1 [], Pub1 []and RSP5 []. All of them contain a HECT domain [].
This alpha helical domain is found in a set of archaeal plasmid replication proteins []. The domain is found to the C terminus of the primase/polymerase domain and is necessary for primase activity. Mutations in this domain can result in defective template binding, dinucleotide formation and conformation change prior to DNA extension.
This family contains a set of membrane proteins, typically 33 amino acids long. The family has no known function, but the protein is found in the operon CydAB in Escherichia coli. Members have a consensus motif (MWYFXW), which is rich in aromatic residues. The protein forms a single membrane-spanning helix. This family seems to be restricted to proteobacteria [].
This entry represents a group of putative plant O-Fucosyltransferases (POFTs), including O-FUCOSYLTRANSFERASE1 (AtOFT1, At3g05320) from Arabidopsis. Interestingly, oft1 mutant pollen tubes are ineffective at penetrating the stigma-style interface leading to a drastic reduction in seed set and a nearly 2000-fold reduction in pollen transmission [, ].
This family represents a set of transmembrane proteins including various interferon-induced transmembrane proteins, synapse differentiation-inducing gene protein 1, and tumor suppressor candidate 5 and homologues. Interferon-induced transmembrane protein 1 (also known as human leukocyte antigen CD225) regulates vesicular membrane fusion events and is essential for different physiological processes such as interferon induced cell growth suppression, neurotransmision and metabolism [, , ].
This family represents the phage-tail-tube protein from a set of Siphoviridae from Gammaproteobacteria. Tail tube proteins (TTPs) polymerise with the assistance of the Tail-tip complex, a tape measure protein and two chaperones. Infectivity of host is delivered through the tube [].
This domain is found in an undescribed set of proteins. It normally occurs uniquely within a sequence, but is found as a tandem repeat (). It has an interesting phylogenetic distribution with the majority of examples in bacteria and archaea, but it is also found in some fungal proteins. The hypothetical protein TT1751 from Thermus thermophilus has a beta-α-β(4)-alpha structural fold [].
This superfamily represents an ~150-amino acid ADF-H (actin-depolymerising factor homology) domain found in three phylogenetically distinct classes of eukaryotic actin-binding proteins [, , ]. This domain shares structural similarity with another set of actin binding proteins, villin and gelsolin, and the C-terminal of the Sec23/Sec24 proteins. It consists of a mixed β-sheet structure.
NCU-G1 is a set of highly conserved nuclear proteins rich in proline with a molecular weight of approximately 44kDa. Especially high levels are detected in human prostate, liver and kidney. NCU-G1 is a dual-function family capable of functioning as a transcription factor as well as a nuclear receptor co-activator by stimulating the transcriptional activity of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) [].
This entry describes a set of polysaccharide biosynthesis/export proteins. Members are variable in either containing or lacking a 78-residue insert, but appear to fall within a single clade. The genomic context of these genes also include genes that encode components of the PEP-CTERM/EpsH (exosortase) protein sorting system.
This entry represents a set of proteins that are part of the wider uracil-xanthine permease family. They are encoded in operons responsible for the import and catabolism of pyrimidines, primarily uracil, and are predicted to function as pyrimidine permeases [, ].
Aminodeoxychorismate synthase, component I (pabB) is closely related to anthranilate synthase component I (trpE). The apparent orthologs of pabB in Aquifex aeolicus and Helicobacter pylori 26695 score well below most TrpE proteins because of a different architecture, in which the less strongly conserved N-terminal domain is absent. The noise cut off is set to exclude most examples of TrpE.
Anthranilate (2-aminobenzoate) is an intermediate of tryptophan (Trp) biosynthesis and degradation. Members of this family are the large subunit of anthranilate 1,2-dioxygenase, which acts in Trp degradation by converting anthranilate to catechol. Closely related paralogs typically are the benzoate 1,2-dioxygenase large subunit, among the larger set of ring-hydroxylating dioxygenases [].
Members of this family are lipoproteins restricted (so far) to the genus Leptospira, sometimes with several paralogues clustered with each other, such as four in a row (out of six) in Leptospira interrogans str. UI 13372. The tandem set may be co-clustered with a putative structural protein that is usually the longest encoded by the leptospiral genome (and that often is an intein-containing protein).
Members of this protein family are found exclusively in genomes that contain putative set of labile selenium-dependent enzyme accessory proteins as well as homologues of a labile selenium-dependent purine hydroxylase. A mutant in this gene in Escherichia coli had improved stationary phase viability. The function of this protein is unknown.
Pre-mRNA splicing is an important step in eukaryotic gene expression. Yeasts and humans share a common set of core spliceosomal proteins that are evolutionarily conserved such as B complex proteins Snu23 (known as ZMAT2 in humans), Prp38 and MFAP1 [, ]. This entry represents Snu23. Its structure has been revealed [, ].
Members of this family consist of a β-sheet region followed by an α-helix and an unstructured C terminus. The β-sheet region contains a CXCX...XCXC sequence with Cys residues located in two proximal loops and pointing towards each other. This precise function of this set of bacterial proteins is, as yet, unknown [].
Members of this occur in gene pairs with members of . The N-terminal region contains several predicted transmembrane helix regions while the few invariant residues (G, CxxD, and W) occur in the C-terminal region. Members of this family are found in a set of prokaryotic hypothetical proteins. Their exact function has not, as yet, been defined.
Members of this family of proteins, with average length of 210, have no invariant residues but five predicted transmembrane segments. Strangely, most members occur in groups of consecutive paralogous genes. A striking example is a set of eleven encoded consecutively, head-to-tail, in Staphylococcus aureus strain COL.
Polycomb repressive complex 2 (PRC2) carries out the methylation of lysine 27 of histone H3, a hallmark of repressive chromatin. Three core subunits make up the catalytic core of PRC2; the SET domain containing EZH2, the zinc-finger containing SUZ12 and the WD40 repeat protein EED. The complex forms a compact arrangement of three lobes. This is the N-terminal domain of EZH2 [].
Like FtsW, SpoVE proteins are encoded in a peptidoglycan operon context, but found only in endospore-forming bacteria such as Bacillus, Geobacillus and Oceanobacillus. In these genera they are part of a larger set of paralogs (not just the pair FtsW and RodA) and are required specifically for sporulation, not for viability.
This domain superfamily is found in an undescribed set of proteins. It normally occurs uniquely within a sequence, but is found as a tandem repeat (). It has an interesting phylogenetic distribution with the majority of examples in bacteria and archaea, but it is also found in Drosophila melanogaster (e.g. ). The hypothetical protein TT1751 from Thermus thermophilus has a beta-α-β(4)-alpha structural fold [].
This group of sequences are a subset of pyruvate dehydrogenase complex dihydrolipoamide acetyltransferase specifically close by both phylogenetic and percent identity (UPGMA) trees. Members contain two or three copies of the lipoyl-binding domain. Escherichia coli AceF is included in this set while mitochondrial and some other bacterial forms are excluded. dihydrolipoyllysine-residue acetyltransferase E2 component of pyruvate dehydrogenase complex
Methyltransferases (EC 2.1.1.-) constitute an important class of enzymespresent in every life form. They transfer a methyl group most frequently fromS-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such asnitrogen, oxygen, sulfur or carbon leading to S-adenosyl-L-homocysteine(AdoHcy) and a methylated molecule. The substrates that are methylated bythese enzymes cover virtually every kind of biomolecules ranging from smallmolecules, to lipids, proteins and nucleic acids. Methyltransferases aretherefore involved in many essential cellular processes includingbiosynthesis, signal transduction, protein repair, chromatin regulation andgene silencing [, , ]. More than 230 different enzymatic reactions ofmethyltransferases have been described so far, of which more than 220 use SAMas the methyl donor [E1]. A review published in 2003 []divides allmethyltransferases into 5 classes based on the structure of their catalyticdomain (fold):class I: Rossmann-like alpha/beta class II: TIM beta/α-barrel alpha/beta class III: tetrapyrrole methylase alpha/betaclass IV: SPOUT alpha/beta class V: SET domainall betaA more recent paper []based on a study of the Saccharomyces cerevisiae methyltransferome argues for four more folds:class VI: transmembrane all alpha class VII: DNA/RNA-binding 3-helical bundle all alpha class VIII: SSo0622-like alpha+beta class IX: thymidylate synthetase alpha+betaThis entry represents the class V proteins, which contain the SET domain usually flanked byother domains forming the so-called pre- and post-SET regions. The enzymesbelonging to this class all N-methylate lysine in proteins. Most of them arehistone methyltransferases (EC 2.1.1.43) like the histone H3-K9methyltransferase dim-5 or the histone H3-K4methyltransferase SETD7 [, ]. Some others methylate thelarge subunit of the enzyme ribulose-bisphosphate-carboxylase/oxygenase(RuBisCO) (EC 2.1.1.127) in plants; in these enzymes the SET domain isinterrupted by a novel domain []. Cytochrome c lysine N-methyltransferases(EC 2.1.1.59) do not possess a SET domain, or at least not a SET domaindetected by any of the detection methods; however they do display a SET-likeregion and for this reason they are also assigned to this class [].
This entry includes ASH1 from flies and ASH1L from mammals. ASH1/ASH1L are the members of the Trithorax family.In Drosophila melanogaster, ASH1 (absent, small, or homeotic 1) is an epigenetic transcriptional regulator of HOX genes. Drosophila ASH1 has been shown to methylate specific lysines in histones H3 and H4. Mammalian ASH1 has been shown to methylate histone H3[, ]. ASH1L methylates Lys36 of histone H3 independently of transcriptional elongation to promote the establishment of Hox gene expression by counteracting Polycomb silencing []. It can suppress interleukin-6 (IL-6), and tumour necrosis factor (TNF) production in Toll-like receptor (TLR)-triggered macrophages, and inflammatory autoimmune diseases by inducing the ubiquitin-editing enzyme A20 []. ASH1L contains an associated with SET domain (AWS), a SET domain, a post-SET domain, a bromodomain, a bromo-adjacent homology domain (BAH), and a plant homeodomain (PHD) finger [].This entry represents the Bromodomain domain of ASH1 and ASH1L.
This entry includes ASH1 from flies and ASH1L from mammals. ASH1/ASH1L are the members of the Trithorax family.In Drosophila melanogaster, ASH1 (absent, small, or homeotic 1) is an epigenetic transcriptional regulator of HOX genes. Drosophila ASH1 has been shown to methylate specific lysines in histones H3 and H4. Mammalian ASH1 has been shown to methylate histone H3[, ]. ASH1L methylates Lys36 of histone H3 independently of transcriptional elongation to promote the establishment of Hox gene expression by counteracting Polycomb silencing []. It can suppress interleukin-6 (IL-6), and tumour necrosis factor (TNF) production in Toll-like receptor (TLR)-triggered macrophages, and inflammatory autoimmune diseases by inducing the ubiquitin-editing enzyme A20 []. ASH1L contains an associated with SET domain (AWS), a SET domain, a post-SET domain, a bromodomain, a bromo-adjacent homology domain (BAH), and a plant homeodomain (PHD) finger [].This entry represents the PHD domain of ASH1 and ASH1L.
Polycomb group (Pc-G) proteins ensure the stable inheritance of expressionpatterns through cell division and regulate the control of cell proliferation.The Enhancer of zeste (E(z))-type of Pc-G proteins includes:Drosophila melanogaster Enhancer of zeste E(z).Mammalian ENX-1 and ENX-2.Arabidopsis thaliana CURLY LEAF (CLF), a transcriptional repressor offloral homeotic gene AGAMOUS.Arabidopsis thaliana CLF-like.Arabidopsis thaliana MEDEA (MEA), a suppressor of endosperm development.Arabidopsis thaliana EZA1.These proteins contain a SET domain at the C terminus.Unique to them is the presence of a CXC domain, an ~65-residue cys-rich regionpreceding the SET domain. The spacing of 17 cyteines is conserved. The CXCdomain contains three units of C-X(6)-C-X(3)-C-X-C motif, although the most C-terminal unit is reverse-oriented. Because of its evolutionary conservation,the CXC domain is likely to be involved in an important function of E(z)-related proteins [, , ].The CXC domain shows some similarity to the CRC domain found in the tesmin/TSO1 protein family [].
This entry represents the PHD finger of A. thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like proteins ATX1, -2, and similar proteins.ATX1 and -2 are sister paralogs originating from a segmental chromosomal duplication; they are plant counterparts of the Drosophila melanogaster trithorax (TRX) and mammalian mixed-lineage leukemia (MLL1) proteins []. ATX1 is a methyltransferase that trimethylates histone H3 at lysine 4 (H3K4me3). It also acts as a histone modifier and as a positive effector of gene expression []. ATX1 regulates transcription from diverse classes of genes implicated in biotic and abiotic stress responses. It is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways []. ATX2 is involved in dimethylating histone H3 at lysine 4 (H3K4me2) []. ATX1 and ATX2 are multi-domain proteins that consist of an N-terminal PWWP domain, FYRN- and FYRC (DAST, domain associated with SET in trithorax) domains, a canonical PHD finger, a non-canonical ePHD finger, and a C-terminal SET domain [].
The enzymes that catalyse histone methylation are classified into 3 families: the PRMT (protein arginine N-methyltransferase) family, the SET-domain-containing family, and the non-SET domain proteins. Lysine 79 (K79) of H3 is methylated by a methyltransferase represented in this entry that lacks a SET domain [].H3K79 methylation occurs in a variety of organisms ranging from yeast to human. In budding yeast, K79 methylation is mediated by the silencing protein Dot1 []. Dot1 homologues can be found in a variety of eukaryotic organisms; in mammals the homologous protein is called Dot1-like protein (DOT1L) [, ]. Dot1/DOT1L catalyses the sequential mono-, di-, and tri-methylation of H3K79, while SET domain-containing methyltransferases mediate methylation in a processive manner []. K79 methylation level is regulated throughout the cell cycle and plays a critical role in the progression of G1 phase, S phase, mitosis, and meiosis [].
In pea (Pisum sativum), the protein-lysine methyltransferase (PsLSMT, also known as RBCMT) catalyses the trimethylation of Lys-14 in the large subunit (LS) of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) []. Arabidopsis homologue of RBCMT, LSMT, is a protein-lysine methyltransferase methylating chloroplastic fructose 1,6-bisphosphate aldolases []. The sequence conservation pattern and structure analysis of the SET domain provides clues regarding the possible active site residues of the domain. There are three conserved sequence motifs in most of the SET domain. The N-terminal motif (I) has characteristic glycines. The central motif (II) has a distinct pattern of polar and charged residues (Asn, His). The C-terminal conserved motif (III) has a characteristic dyad of polar residues and the hydrophobic residue tyrosine.
Enzymes in the galactarate dehydratase 2 family catalyze the dehydration of galactarate. The product of this reaction is the enantiomer of the product of the galactarate dehydratase reaction catalyzed by the L-talarate/galactarate dehydratase family in the mandelate racemase subgroup. Though the overall reaction catalyzed is the same as that of enzymes in the galactarate dehydratase 3 family, a distinct set of catalytic residues are used by enzymes in families 2 and 3 [].galactarate(2-) ->3-deoxy-D-threo-hex-2-ulosarate(2-) + H2O
A fairly deep split separates this polyprenyltransferase subfamily from the set of mitochondrial and proteobacterial 4-hydroxybenzoate polyprenyltransferases, described in . Protoheme IX farnesyltransferase (heme O synthase) () is more distantly related. Because no species appears to have both this protein and a member of , it is likely that this family of sequences represent 4-hydroxybenzoate polyprenyltransferase, a critical enzyme of ubiquinone biosynthesis, in the Archaea, Gram-positive bacteria, Aquifex aeolicus, and the Chlamydias.
The predicted protein-sorting transpeptidase that we call exosortase (see ) has distinct subclasses that associated with different types of exopolysaccharide production loci. This entry represents a distinct clade among a set of amidotransferases largely annotated (not necessarily accurately) as glutamine-hydrolysing asparagine synthases. Members of this clade are essentially restricted to the characteristic exopolysaccharide (EPS) regions that contain the exosortase 1 genome (xrtA), in genomes that also have numbers of PEP-CTERM domain () proteins.
This entry represents a set of bacterial HORMA domains found in proteins from the CBASS (cyclic oligonucleotide-based antiphage signaling system), a system that provides immunity against bacteriophage. This domain is found in CD-NTase-associated protein 7 (Cap7) from E.coli, that acts as a sensor protein of CBSS and binds to a closure peptide allowing it to activate the CD-NTase CdnC for second messenger synthesis and, therefore, it activates a diverse range of effectors [, ].
Histone-lysine N-methyltransferase 2A (KMT2A; ) is the catalytic subunit of the MLL1/MLL complex, mediating methylation of 'Lys-4' of histone H3 (H3K4me), a specific tag for epigenetic transcriptional activation []. KMT2A is processed by the threonine endopeptidase taspase, releasingproducts N320 and C180 []. KMT2A contains a CxxC (x for any residue) zinc finger domain, three plant homeodomain (PHD) fingers, a Bromodomain domain, an extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain.
SAM domains are found in a diverse set of proteins, which include scaffolding proteins, transcription regulators, translational regulators tyrosine kinases and serine/threonine kinases. Structures of SAM domains reveal a common five helical structure. The SAM domain is involved in a variety of functions. The most widespread function is in domain-domain interactions. This SAM (sterile alpha motif) domain is found in epidermal growth factor receptor kinase substrate (EPS8) and other proteins.
This entry includes a set of Actinobacterial proteins, including Rv2632c from Mycobacterium tuberculosis that is strongly implicated in the onset of non-replicating persistence, and thereby latent tuberculosis. Rv2632c contains a dsRBD-like (2 layers alpha/beta) fold (PDBe:2fgg). It shares remarkable similarity with bacterial hibernation factors, despite very low sequence similarity. Based on this structure it was predicted that Rv1738, highly up-regulated in conditions that mimic the onset of persistence, helps trigger dormancy by association with the bacterial ribosome [].
This entry represents the ePHD finger of A. thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like proteins ATX3, ATX4 and ATX5, which belong to the histone-lysine methyltransferase family. The extended plant homeodomain (ePHD) zinc finger is characterised as Cys2HisCys5HisCys2His.These proteins show distinct phylogenetic origins from the family of ATX1 and ATX2. They are multi-domain proteins that consist of an N-terminal PWWP domain, a canonical PHD finger, a non-canonical extended PHD (ePHD) finger, and a C-terminal SET domain [, ].
Cell cycle and apoptosis regulator protein 2 (CCAR2, also known as DBC-1) regulates biological processes such as transcription, heterochromatin formation, metabolism, mRNA splicing, apoptosis, and cell proliferation []. It is a core component of the DBIRD complex, which affects local transcript elongation rates and alternative splicing of a large set of exons embedded in (A + T)-rich DNA regions []. It binds to SIRT1 and is a negative regulator of SIRT1 []. DBC-1 has been implicated in tumorigenesis [].
This family consists of several related groups of proteins, one of which is the LptC family. LptC is involved in lipopolysaccharide-assembly on the outer membrane of Gram-negative organisms []. The lipopolysaccharide component of the outer bacterial membrane is transported form its source of origin to the outer membrane by a set of proteins constituting a transport machinery that is made up of LptA, LptB, LptC, LptD, LptE. LptC is located on the inner membrane side of the intermembrane space.
Class V myosins are well studied unconventional myosins, represented by three paralogs (Myo5a,b,c) in vertebrates. Their C-terminal cargo binding domains (CBDs) are important for the binding of a diverse set of cargos, including membrane vesicles, organelles, proteins and mRNA. They interact with several adaptor proteins, in case of Myo5a-CBD, melanophilin (MLPH), Rab interacting lysosomal protein-like 2 (RILPL2), and granuphilin []. Mutations in human Myo5a (many of which map to the cargo binding domain) lead to Griscelli syndrome, a severe neurological disease [].
Class V myosins are well studied unconventional myosins, represented by three paralogues (Myo5a,b,c) in vertebrates. Their C-terminal cargo binding domains (CBDs) are important for the binding of a diverse set of cargos, including membrane vesicles, organelles, proteins and mRNA. The Myo5-CBDs directly interact with several adaptor proteins [, ]. Myo5b and myo5c are primarily expressed in epithelial cells, and have been implicated as motors involved in recycling endosomes [].
This domain is found in a set of closely related proteins including the (R)-2-hydroxyglutaryl-CoA dehydratase activase of Acidaminococcus fermentans, in longer proteins from Methanocaldococcus jannaschii (Methanococcus jannaschii) and Methanobacterium thermoautotrophicum that share an additonal N-terminal domain, in a protein described as a subunit of the benzoyl-CoA reductase of Rhodopseudomonas palustris, and in two repeats of an uncharacterised protein of Aquifex aeolicus. This domain may be involved in generating or regenerating the active sites of enzymes related to (R)-2-hydroxyglutaryl-CoA dehydratase and benzoyl-CoA reductase.
The family of myotubularin (MTM) phosphoinositide phosphatases includes catalytically inactive members, or pseudophosphatases, which contain inactivating substitutions in the phosphatase domain []. Myotubularin-related protein 10 (MTMR10) is a probable pseudophosphatase.MTMR10 contains an N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an inactive PTP domain, and a SET interaction domain. It contains a Glu residue instead of a conserved Cys residue in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase. This entry represents the PH-GRAM domain of MTMR10.
This domain represents the C-terminal region of vertebrate heat shock transcription factors. Heat shock transcription factors regulate the expression of heat shock proteins - a set of proteins that protect the cell from damage caused by stress and aid the cell's recovery after the removal of stress []. This C-terminal region is found with the N-terminal , and may contain a three-stranded coiled-coil trimerisation domain and a CE2 regulatory region, the latter of which is involved in sustained heat shock response [].
This short presumed domain is about 50 amino acid residues long. It often contains two cysteines that may be functionally important. This domain is found in cation transporting ATPases, some oxygenase components of multicomponent enzymatic monooxigenases, and in a set of uncharacterised membrane proteins including . This domain is named after three of the most conserved amino acids it contains. The domain may be metal binding. This domain is duplicated in some copper transporting ATPases.
This is a highly conserved set of proteins which contains three pairs of cysteine residues within a length of 42 amino acids and is rich in proline residues towards the N terminus. It includes a membrane protein that has been found to be highly expressed in the mouse brain and consequently, several members have been assigned as brain protein i3 (Bri3) []. Their function is unknown but they appear to play a role in TNF-induced cell death [].
Members of this family are VapC proteins that consist almost entirely of a PIN (PilT N terminus) domain. This family was originally defined a set of twelve closely related paralogs found in Mycobacterium tuberculosis, but additional members are found now Synechococcus sp. WH8102, etc. This family includes ribonucleases VapC24 and Vap25 among others. They are the toxic component of a toxin-antitoxin (TA) module. They act as an RNase and all their toxic effects are neutralised by coexpression with cognate antitoxin [].
The soluble ligand-binding β-grasp domain (SLBB) contains a β-grasp fold. They are found in a diverse set of proteins that include the animal vitamin B12 uptake proteins; transcobalamin, intrinsic factor and the bacterial polysaccharide export proteins []. Some proteins may be part of a membrane complex involved in electron transport, others are probably involved in the export of the extracellular polysaccharide colanic acid from the cell to medium.
This is the helicase associated domain (HA2) found as a diverse set of RNA helicases. It has an all α-helical fold that can be divided in two subdomains, an N-terminal degenerated winged helix (WH) and a C-terminal ratchet-like domain [, , , ]. This domain collaborates with the RecA domains at the N-terminal in the formation of a RNA binding channel to allow the helicases to keep a stable grip on the RNA.
This entry represents the PHD finger of A. thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like proteins ATX3, ATX4 and ATX5, which belong to the histone-lysine methyltransferase family.These proteins show distinct phylogenetic origins from the family of ATX1 and ATX2. They are multi-domain proteins that consist of an N-terminal PWWP domain, a canonical PHD finger, a non-canonical extended PHD (ePHD) finger, and a C-terminal SET domain [, ].
Transcription of all the members of MHCII family of genes is controlled by a set of conserved transcription factors and promoter elements. One of these class II transactivators is the DNA-binding RFX complex, which consists of subunits RFX5 and its accessory proteins RFXAP and RFXANK [].This entry represents the C-terminal domain of RFX5. The C-terminal domain mediates cooperative binding between the RFX complex and NF-Y, a transcription factor binding to the Y box sequence of MHC-II promoters [].
It has been estimated that just over ten percent of all genome-sequenced prokaryotes, including most actinomycetes, use F420 as a redox coenzyme. This entry represents a set of predicted F420-binding enzymes. The Rv1155 protein from Mycobacterium tuberculosis has been crystallised and its structure shown to broadly resemble that of FMN-binding proteins, though it contains an empty cleft corresponding to, yet differing to the FMN-binding site of pyridoxine 5'-phosphate oxidase [].
Members of this protein family represent a distinct clade among the larger set of proteins that belong to . Proteins from this clade are found in genome sequence if and only if the species sequenced is one of the methanogens. All methanogens belong to the archaea; some but not all of those sequenced are hyperthermophiles. This protein family was detected by the method of partial phylogenetic profiling [].
This entry includes a set of Actinobacterial proteins, including Rv2632c from Mycobacterium tuberculosis that is strongly implicated in the onset of non-replicating persistence, and thereby latent tuberculosis. Rv2632c contains a dsRBD-like (2 layers alpha/beta) fold (PDBe:2fgg). It shares remarkable similarity with bacterial hibernation factors, despite very low sequence similarity. Based on this structure it was predicted that Rv1738, highly up-regulated in conditions that mimic the onset of persistence, helps trigger dormancy by association with the bacterial ribosome [].
Members of this entry are a set of functionally uncharacterised hypothetical bacterial proteins. They adopt a ferredoxin-like fold, with a beta-α-β-beta-α-β arrangement []. This entry contains the protein Impact, which is a translational regulator that ensures constant high levels of translation under amino acid starvation. It acts by interacting with Gcn1/Gcn1L1, thereby preventing activation of Gcn2 protein kinases (EIF2AK1 to 4) and subsequent down-regulation of protein synthesis. It is evolutionary conserved from eukaryotes to archaea [].
This entry represents WetA and related proteins mostly from fungi. BrlA, abaA and wetA are pivotal regulators of conidiophore development and conidium maturation. They act individually and together to regulate their own expression and that of numerous other sporulation-specific genes []. WetA is responsible for activating a set of genes whose products make up the final two conidial wall layers or direct their assembly and, through this activity, is responsible for acquisition of spore dormancy [, , ].
Arteriviruses are small, enveloped, animal viruses with an icosahedral core containing a positive-sense RNA genome. The arteriviruses are highly species specific, but share many biological and molecular properties, including virion morphology, a unique set of structural proteins, genome organisation and replication strategy. This is a family of minor envelope glycoproteins from Arteriviridae that corresponds to open reading frame 4 (ORF4) of the virus [, ].
This is the N-terminal domain of human co-chaperone protein HscB (hHscB). This domain is capable of binding a metal ion through its tetracysteine metal binding motif. The metal atom is coordinated by a set of four cysteine residues (Cys41, Cys44, Cys58 and Cys61) on opposed β-hairpins. Although the N-domain lacks anyrecognizable secondary structure elements, it has several distant structural homologs including C-4 zinc finger domains and rubredoxin [].
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide isomerase (), also known as Phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase or HisA, catalyses the fourth step in histidine biosynthesis. HisA from Lactococcus lactis was found to be inactive []. The putative HisA from Thermotoga maritima, is a conspicuous outlier to the set of all other HisA, including experimental HisA from the bacterium Escherichia coli and the Archaeaon Methanococcus voltae. Neighbour joining shows HisA from Thermotoga maritima to be within the HisA family (with HisF as an outgroup) but with a long branch.
Members of this protein family are similar in length and sequence (although remotely) to the WXG100 family of type VII secretion system (T7SS) targets. Phylogenetic profiling shows that members of this family are similarly restricted to species with T7SS, marking this family as a related set of T7SS effectors. Members include SACOL2603 from Staphylococcus aureus subsp. aureus COL. Oddly, members of family (DUF2580), which appears also to be related, seem not to be tied to T7SS.
This domain is localized to the central region of a set of LPS (lipopolysaccharide)-assembly protein LptD that likely represents the LptD homologue of Bacteroidetes.LptD forms a complex with LptE, which is involved in the assembly of LPS in the outer leaflet of the outer membrane. It determines N-hexane tolerance and is involved in outer membrane permeability as well as being ssential for envelope biogenesis [, , ].
These represent DnaQ, the DNA polymerase III epsilon subunit, as found in most Proteobacteria. It consists largely of an exonuclease region as described in . In Gram-positive bacteria, closely related regions are found both in the Gram-positive type DNA polymerase III alpha subunit and as an additional N-terminal domain of a DinG-family helicase. Both are not included in this set of sequences, as they are smaller proteins.
This domain is found in the Zc3h12a protein and NEDD4-binding protein 1. Zc3h12a has been shown to be a ribonuclease that controls the stability of a set of inflammatory genes []. NEDD4-binding protein 1 is a potent suppressor of cytokine production that acts as a regulator of innate immune signaling and inflammation []. This domain belongs to the PIN domain superfamily []and it has also been identified as part of the NYN domain family [].
SETD3 is a protein-histidine N-methyltransferase that specifically mediates methylation of actin at 'His-73' []. It was initially reported to have histone methyltransferase activity and methylate 'Lys-4' and 'Lys-36' of histone H3 (H3K4me and H3K36me). However, this conclusion was based on mass spectrometry data wherein mass shifts were inconsistent with a bona fide methylation event. In vitro, the protein-lysine methyltransferase activity is weak compared to the protein-histidine methyltransferase activity [].Methyltransferases (EC [intenz:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule [, , ]. All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM []. The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids [, , ]. Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing [, , ]. More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.A review published in 2003 []divides allmethyltransferases into 5 classes based on the structure of their catalyticdomain (fold):class I: Rossmann-like alpha/betaclass II: TIM beta/α-barrel alpha/betaclass III: tetrapyrrole methylase alpha/betaclass IV: SPOUT alpha/beta class V: SET domain all betaA more recent paper []based on a study of the Saccharomyces cerevisiaemethyltransferome argues for four more folds:class VI: transmembrane all alpha class VII: DNA/RNA-binding 3-helical bundle all alphaclass VIII: SSo0622-like alpha betaclass IX: thymidylate synthetase alpha betaClass V proteins contain the SET domain usually flanked byother domains forming the so-called pre- and post-SET regions. Except themembers of the STD3 family which N-methylate histidine in beta-actin (EC2.1.1.85) [, ], enzymes belonging to this class N-methylatelysine in proteins. Most of them are histone methyltransferases (EC 2.1.1.43)like the histone H3-K9 methyltransferase dim-5 or the histoneH3-K4 methyltransferase SETD7 [, ]. Some others methylatethe large subunit of the enzyme ribulose-bisphosphate-carboxylase/oxygenase(RuBisCO) (EC 2.1.1.127) in plants; in these enzymes the SET domain isinterrupted by a novel domain []. Cytochrome c lysine N-methyltransferases(EC 2.1.1.59) do not possess a SET domain, or at least not a SET domaindetected by any of the detection methods; however they do display a SET-likeregion and for this reason they are also assigned to this class [].
This group of sequences represent the acyl carrier protein (gamma subunit) of the holoenzyme citrate lyase () composed of alpha (), beta (), and acyl carrier protein subunits in a stoichiometric relationship of 6:6:6. Citrate lyase is an enzyme which converts citrate to oxaloacetate. In bacteria, this reaction is involved in citrate fermentation. The acyl carrier protein covalently binds the coenzyme of citrate lyase. The set contains an experimentally characterised member from Leuconostoc mesenteroides []. The sequences come from a wide range of Gram-positive bacteria. For Gram-negative bacteria, it appears that only sequences from the gamma proteobacteria are included.
This entry represents a set of bacterial lipoproteins belonging to a larger acid phosphatase family (), which in turn belongs to the haloacid dehalogenase (HAD) superfamily of aspartate-dependent hydrolases. Members are found on the outer membrane of Gram-negative bacteria and the cytoplasmic membrane of Gram-positive bacteria. Most members have classic lipoprotein signal sequences. A critical role of this 5'-nucleotidase in Haemophilus influenzae is the degradation of external riboside in order to allow transport into the cell. An earlier suggested role in hemin transport is no longer current. This enzyme may also have other physiologically significant roles [].
This family consists of the fungal C-8 sterol isomerase and mammalian sigma1 receptor. C-8 sterol isomerase (delta-8--delta-7 sterol isomerase), catalyses a reaction in ergosterol biosynthesis, which results in unsaturation at C-7 in the B ring of sterols []. Sigma 1 receptor is a low molecular mass mammalian protein located in the endoplasmic reticulum [], which interacts with endogenous steroid hormones, such as progesterone and testosterone []. It also binds the sigma ligands, which are a set of chemically unrelated drugs including haloperidol, pentazocine, and ditolylguanidine []. Sigma1 effectors are not well understood, but sigma1 agonists have been observed to affect NMDA receptor function, the alpha-adrenergic system and opioid analgesia.
Histone-lysine N-methyltransferase EHMT1, () mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin []. H3K9me is a specific tag for repression of epigenetic transcription, recruiting HP1 proteins to methylated histones. EHMT1 also methylates 'Lys-27' of histone H3 (H3K27me), but weakly []. EHMT1 also dimethylates other proteins, including 'Lys-373' of p53 []. EHMT1 forms a heterodimer with EHMT2 [], and is a component of the E2F6.com-1 complex in G0 phase []. EHMT1 contains eight ankyrin repeats which bind the monomethylated RELA subunit of NF-kappa-B, a SET domain which interacts with WIZ [], and a pre-SET domain that binds three zinc ions via cysteine residues [].
Histone-lysine N-methyltransferase EHMT1, () mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin []. H3K9me is a specific tag for repression of epigenetic transcription, recruiting HP1 proteins to methylated histones. EHMT1 also methylates 'Lys-27' of histone H3 (H3K27me), but weakly []. EHMT1 also dimethylates other proteins, including 'Lys-373' of p53 []. EHMT1 forms a heterodimer with EHMT2 [], and is a component of the E2F6.com-1 complex in G0 phase []. EHMT1 contains eight ankyrin repeats which bind the monomethylated RELA subunit of NF-kappa-B, a SET domain which interacts with WIZ [], and a pre-SET domain that binds three zinc ions via cysteine residues [].
This is an NSD-specific Cys-His rich region (C5HCH) domain. Proteins containing this domain include NSD (nuclear receptor SET domain-containing) proteins. This domain is located on the C-terminal of NSD1, 2 and 3 proteins. C5HCH domain lies adjacent to the fifth plant homeodomain (PHD5). The PHD5-C5HCH module of NSD3 (PHD5-C5HCHNSD3) recognises the H3 N-terminal peptide containing unmodified K4 and trimethylated K9. Moreover, it has been reported that the PHD5-C5HCH module of NSD1 (PHD5-C5HCH) was the sole region required for tight binding of the NUP98-NSD1 fusion protein to the HoxA9 gene promoter, implicating that PHD5-C5HCH might have chromatin targeting ability [].
This entry represents the phosphatase domain of the human RNA polymerase II subunit A C-terminal domain phosphatase (FCP1, []) and closely related phosphatases from eukaryotes including plants, fungi []and slime mold. This domain is a member of the haloacid dehalogenase (HAD) superfamily by virtue of a conserved set of three catalytic motifs []and a conserved fold as predicted by PSIPRED. The third motif in this family is distinctive (hhhhDDppphW). This domain is classified as a "Class III"HAD, since there is no large "cap"domain found between motifs 1 and 2 or motifs 2 and 3 []. This domain is related to domains found in the human NLI interacting factor-like phosphatases.
In prokaryotes, the incorporation of selenocysteine as the 21st amino acid, encoded by TGA, requires several elements: SelC is the tRNA itself, SelD acts as a donor of reduced selenium, SelA modifies a serine residue on SelC into selenocysteine, and SelB is a selenocysteine-specific translation elongation factor. 3-prime or 5-prime non-coding elements of mRNA have been found as probable structures for directing selenocysteine incorporation []. This family describes SelA. A close homologue of SelA is found in Helicobacter pylori, but all other required elements are missing and the protein is shorter at the N terminus than SelA from other species. The trusted cut-off is set above the score generated for Helicobacter pyloriputative SelA.
Members of this protein family are HemK, a protein once thought to be involved in heme biosynthesis but now recognised to be a protein-glutamine methyltransferase that modifies the peptide chain release factors []. All members of the seed alignment are encoded next to the release factor 1 gene (prfA) and confirmed by phylogenetic analysis. However, the family is diverse enough that even many members of the seed alignment do not score above the seed alignment, which was set high enough to exclude all instances of PrmB.
This entry represents a group of proteins based on a PfaB protein family. The protein PfaB family is part of a four-gene locus, which is similar to polyketide biosynthesis systems, responsible for omega-3 polyunsaturated fatty acid biosynthesis in several high pressure and/or cold-adapted bacteria. The fairly permissive trusted cut off set for this HMM allows detection of homologues encoded near homologues to other proteins of the locus: PfaA, PfaC, and/or PfaD. The likely role in every case is either polyunsaturated fatty acid or polyketide biosynthesis.
This entry represents a family that includes methylenetetrahydrofolate reductase.The enzyme activities methylenetetrahydrofolate reductase () and 5,10-methylenetetrahydrofolate reductase (FADH) () differ in that the former (assigned in many eukaryotes) is defined to use NADP+ as an acceptor, while the latter (assigned in many bacteria) is flexible with respect to the acceptor. Both convert 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. From a larger set of proteins assigned as one or the other, this family describes the subset of proteins found in eukaryotes, and currently designated methylenetetrahydrofolate reductase(). This protein is an FAD-containing flavoprotein.
This entry represents a family that includes bacterial 5,10-methylenetetrahydrofolate reductase (FADH).The enzyme activities methylenetetrahydrofolate reductase () and 5,10-methylenetetrahydrofolate reductase (FADH) () differ in that the former (assigned in many eukaryotes) is defined to use NADP+ as an acceptor, while the latter (assigned in many bacteria) is flexible with respect to the acceptor. Both convert 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. From a larger set of proteins assigned as one or the other, this family describes the subset of proteins found in prokaryotes, and currently designated 5,10-methylenetetrahydrofolate reductase (FADH) (). This protein is an FAD-containing flavoprotein.
Eukaryotic 4-aminobutyrate aminotransferase () is a class III pyridoxal-phosphate-dependent aminotransferase. The enzyme catalyses the conversion of 4-aminobutanoate and 2-oxoglutarate into succinate semialdehyde and L-glutamate. The degree of sequence difference between this set and known bacterial examples is greater than the distance between, in either set, the most similar enzyme with a distinct function, and so the prokaryotic and eukaryotic sets have been placed into separate families. This family describes known bacterial examples of the enzyme. The best archaeal matches arepresumed but not trusted to have the equivalent function. Escherichia coli has two isozymes. Alternate names include GABA transaminase, gamma-amino-N-butyrate transaminase, and beta-alanine--oxoglutarate aminotransferase.
Several bacteria and archaea utilize the amino group-carrier protein, LysW, for lysine biosynthesis from alpha-aminoadipate (AAA). In some cases, such as Sulfolobus, LysW is also used to protect the amino group of glutamate in arginine biosynthesis. After LysW modification, AAA and glutamate are converted to lysine and ornithine, respectively, by a single set of enzymes with dual functions [].LysK catalyzes the release of L-lysine from [LysW]-gamma-L-lysine in the lysine biosynthetic pathway and the release of L-ornithine from [LysW]-L-ornithine in the arginine biosynthetic pathway [].
Peroxisomal acyl-CoA oxidases (ACO) catalyze the first set in the peroxisomal fatty acid beta-oxidation, the alpha,beta dehydrogenation of the corresponding trans-enoyl-CoA by FAD, which becomes reduced. In a second oxidative half-reaction, the reduced FAD is reoxidized by molecular oxygen. ACO is generally a homodimer. There are several subtypes of AXO's, based on substrate specificity. Palmitoyl-CoA oxidase (ACOX1) acts on straight-chain fatty acids and prostanoids [, ]; whereas, the closely related Trihydroxycoprostanoly-CoA oxidase (ACOX2) has the greatest activity for 2-methyl branched side chains of bile precursors []. Pristanoyl-CoA oxidase (ACOX3), acts on 2-methyl branched fatty acids [, ].
Fatty acid synthesis involves a set of reactions, starting with carboxylation of acetyl-CoA to malonyl-CoA. This is an irreversible reaction, catalysed by the acetyl-CoA carboxylase complex (); a heterohexamer of biotin carboxyl carrier protein, biotin carboxylase and two non-identical carboxyl transferase subunits (alpha and beta) in a 2:2 association []. The reaction involves two steps:Biotin carrier protein + ATP + HCO3-= Carboxybiotin carrier protein + ADP + PiCarboxybiotin carrier protein + Acetyl-CoA = Malonyl-CoA + Biotin carrier proteinIn the first step, biotin carboxylase catalyses the carboxylation of the carrier protein to form an intermediate. Next, the transcarboxylase complex transfers the carboxyl group from the intermediate to acetyl-CoA forming malonyl-CoA.
PRDM2 (also known as RIZ) is a transcriptional regulator and tumour suppressor that catalyzes methylation of lysine 9 of histone H3. Its PR domain is responsible for its catalytic activity []. PRDM2 belongs to the PRDM family, whose members are characterised by the presence of an N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains []. PRDM2 interacts with another tumour suppressor, the retinoblastoma protein (Rb). A short motif, IRCDE, in the acidic region (AR) of RIZ is important for this interaction [].
The COMPASS complex (complex proteins associated with Set1p) is conserved in yeasts and in other eukaryotes up to humans. The COMPASS complex functions to methylate the fourth lysine of Histone 3 and for the silencing of genes close to the telomeres of chromosomes []. Five domains are conserved in Saccharomyces cerevisiae Set1 and other eukaryotic Set1-related proteins: an amino-terminal RNA-recognition motif (RRM), a semi-conserved central domain, an N-SET domain, the catalytic SET domain, and the C-terminal post-SET domain. This entry represents the N-SET domain, which promotes trimethylation in conjunction with the RRM domain []and is necessary for binding of the Spp1 component of COMPASS into the complex [].
This superfamily of short proteins includes DNA-damage-inducible protein I (DinI) and related proteins. The SOS response, a set of cellular phenomena exhibited by eubacteria, is initiated by various causes that include DNA damage-induced replication arrest, and is positively regulated by the co- protease activity of RecA. Escherichia coli DinI, a LexA-regulated SOS gene product, shuts off the initiation of the SOS response when overexpressed in vivo. Biochemical and genetic studies indicated that DinI physically interacts with RecA to inhibit its co-protease activity []. The structure of DinI is known [].
This family of short proteins includes DNA-damage-inducible protein I (DinI) and related proteins. The SOS response, a set of cellular phenomena exhibited by eubacteria, is initiated by various causes that include DNA damage-induced replication arrest, and is positively regulated by the co- protease activity of RecA. Escherichia coli DinI, a LexA-regulated SOS gene product, shuts off the initiation of the SOS response when overexpressed in vivo. Biochemical and genetic studies indicated that DinI physically interacts with RecA to inhibit its co-protease activity []. The structure of DinI is known [].
These enzymes are involved in the repair of UV radiation-induced DNA damage during spore germination. They can repair thymine dimer 5-thyminyl-5,6-dihydrothymine (known as spore photoproduct (SP)) by in situ monomerization of spore photoproduct to two thymines. This family of enzymes uses the SAM as a cofactor (rather than in a stoichiometric manner). This set of SPL enzymes is distinguished from the other SPL family because its fourth conserved Cys residue occurs before the CxxxCxxC motif, unlike in the other SPL family, in which is occurs after the CxxxCxxC motif [].This entry represents spore photoproduct lyases mostly from Clostridia.
Histone-lysine N-methyltransferase 2A (KMT2A; ) is the catalytic subunit of the MLL1/MLL complex, mediating methylation of 'Lys-4' of histone H3 (H3K4me), a specific tag for epigenetic transcriptional activation []. KMT2A is processed by the threonine endopeptidase taspase, releasing products N320 and C180 []. KMT2A contains a CxxC (x for any residue) zinc finger domain, three plant homeodomain (PHD) fingers, a Bromodomain domain, an extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain.This entry represents the third PHD domain of KMT2A.
EIF2B is the guanine nucleotide exchange factor for protein synthesis initiation factor 2 (eIF2). EIF2B is a complex multimeric protein consisting of five subunits named alpha, beta, gamma, delta and epsilon. The epsilon and gamma subunits are sequence similar and both are essential in yeast. Epsilon appears to be the catalytically active subunit, with gamma enhancing its activity []. The C-terminal domain of the eIF2B epsilon subunit contains bipartite motifs rich in acidic and aromatic residues. It is required for both catalytic activity and interaction with eIF2. The structure of the domain resembles that of a set of concatenated HEAT repeats [, ].
This protein family represents Taxis protein CheF1/F2 from Halobacterium salinarum and similar proteins found in archaea. CheF1/2 are archaea-specific adaptor proteins that link the bacterial-like chemotaxis signal transduction system to the archaeal motility machinery [, ].CheF1 interact with the chemotaxis proteins CheY, CheD and CheC2 as well as the flagella-accessory proteins FlaCE and FlaD, and is essential for any tactic response. This protein is conserved in almost all chemotactic archaea.CheF2 is found in a very limited set of haloarchaea and is thought to have a less important role in chemotaxis [].
The enoyl-CoA hydratase/isomerase family contains a diverse set of enzymes including: enoyl-CoA hydratase, napthoate synthase, carnitate racemase, 3-hydroxybutyryl-CoA dehydratase and dodecanoyl-CoA delta-isomerase. This entry represents a subset of the enoyl-CoA hydratase/isomerase family. Proteins in this entry includes 3-hydroxyisobutyryl-CoA hydrolases (HIBYL-CoA-H) from eukaryotes and their homologues from bacteria. Human HIBYL-CoA-H is a mitochondrial enzyme that catalyses the fifth step in the valine catabolic pathway in eukaryotes, namely the conversion of 3-hydroxyisobutyryl-CoA to free 3-hydroxyisobutyrate [, ]. It also hydrolyses 3-hydroxypropionyl-CoA, giving it a dual role in a secondary pathway of propionate metabolism []. Deficiency of this enzyme is associated with Leigh-like disease [, ].
This entry represents the PR/SET domain found in PR domain zinc finger protein 2 (PRDM2, also known as RIZ1). PRDM2 is S-adenosyl-L-methionine-dependent histone methyltransferase that specifically methylates 'Lys-9' of histone H3 [, ].The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains []. They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes [].
This entry represents the PR/SET domain found in PR domain zinc finger protein 17 (PRDM17, also known as ZNF408). Its function is not clear.The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains []. They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes [].
This entry represents the PR/SET domain found in PR domain zinc finger protein 15 (PRDM15). PRDM15 plays an essential role as a chromatin factor that modulates the transcription of upstream regulators of WNT and MAPK-ERK signaling to safeguard naive pluripotency [].The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains []. They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes [].
This entry represents the PR/SET domain found in PR domain zinc finger protein 11 (PRDM11). PRDM11 is a putative tumour suppressor that controls the expression of key oncogenes [].The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains []. They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes [].
This entry represents the PR/SET domain found in PR domain zinc finger protein 10 (PRDM10). PRDM10 may be involved in transcriptional regulation [, , ].The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains []. They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes [].
This entry represents the PR/SET domain found in PR domain zinc finger protein 4 (PRDM4). PRDM4 may function as a transcription factor that recruits protein arginine methyltransferase 5 (PRMT5) to mediate histone arginine methylation and control neural stem cell proliferation and differentiation [].The PRDM family members are characterised by the presence of a N-terminal PR (PRDI-BF1 and RIZ1 homology) domain followed by multiple zinc fingers which confer DNA binding activity. PR domains are only distantly related to the classical SET methyltransferase domains []. They are involved in epigenetic regulation of gene expression through their intrinsic histone methyltransferase activity or via interactions with other chromatin modifying enzymes [].
