This entry represents the N-terminal region of muskelin and is found in conjunction with several
repeats. Muskelin is an intracellular, kelch repeat protein that is needed in cell-spreading responses to the matrix adhesion molecule, thrombospondin-1 [
].
This family consists of a number of bacteria specific domains, which are found in haemolysin-type calcium binding proteins. This family is found in conjunction with
and is often found in multiple copies.
Myotubularin-related protein 4, protein tyrosine phosphatase domain
Type:
Domain
Description:
Myotubularin-related protein 4 (MTMR4) is a member of the myotubularin (MTM) family. It is the only family member that possesses a FYVE domain (a zinc finger domain) at its C terminus [
]. MTMR4 has dual-specificity phosphatase activity []; some studies have shown that it can dephosphorylate PI3P or PI(3,5)P2, suggesting that MTMR4 is also a lipid phosphatase []. MTMR4 has a unique distribution to endosomes [] and has been shown to function in early and recycling endosomes [,
]. MTMR4 attenuates TGF-beta signalling by dephosphorylating intracellular signalling mediator R-Smads []. Similarly, it acts as a negative modulator for the homeostasis of bone morphogenetic proteins (BMPs) signalling [].The myotubularin family constitutes a large group of conserved proteins, with 14 members in humans consisting of myotubularin (MTM1) and 13 myotubularin-related proteins (MTMR1-MTMR13). Orthologues have been found throughout the eukaryotic kingdom, but not in bacteria. MTM1 dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) to phosphatidylinositol and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] to phosphatidylinositol 5-monophosphate (PI5P) [,
]. The substrate phosphoinositides (PIs) are known to regulate traffic within the endosomal-lysosomal pathway []. MTMR1, MTMR2, MTMR3, MTMR4, and MTMR6 have also been shown to utilise PI(3)P as a substrate, suggesting that this activity is intrinsic to all active family members. On the other hand, six of the MTM family members encode for catalytically inactive phosphatases. Inactive myotubularin phosphatases contain substitutions in the Cys and Arg residues of the Cys-X5-Arg motif. MTM pseudophosphatases have been found to interact with MTM catalytic phosphatases []. The myotubularin family includes several members mutated in neuromuscular diseases or associated with metabolic syndrome, obesity, and cancer [].This entry represents the active Protein Tyrosine Phosphatase (PTP) domain of MTMR4.
Myotubularin-related protein 7, protein tyrosine phosphatase domain
Type:
Domain
Description:
Myotubularin-related protein 7 (MTMR7) is a member of the myotubularin (MTM) family. MTMR9 is a binding partner of MTMR7, and binding of MTMR9 increases the phosphatase activity of MTMR7 [
]. MTMR9 and MTMR7 may be involved in regulating T-helper (Th) cells differentiation [].The myotubularin family constitutes a large group of conserved proteins, with 14 members in humans consisting of myotubularin (MTM1) and 13 myotubularin-related proteins (MTMR1-MTMR13). Orthologues have been found throughout the eukaryotic kingdom, but not in bacteria. MTM1 dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) to phosphatidylinositol and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] to phosphatidylinositol 5-monophosphate (PI5P) [,
]. The substrate phosphoinositides (PIs) are known to regulate traffic within the endosomal-lysosomal pathway []. MTMR1, MTMR2, MTMR3, MTMR4, and MTMR6 have also been shown to utilise PI(3)P as a substrate, suggesting that this activity is intrinsic to all active family members. On the other hand, six of the MTM family members encode for catalytically inactive phosphatases. Inactive myotubularin phosphatases contain substitutions in the Cys and Arg residues of the Cys-X5-Arg motif. MTM pseudophosphatases have been found to interact with MTM catalytic phosphatases []. The myotubularin family includes several members mutated in neuromuscular diseases or associated with metabolic syndrome, obesity, and cancer [].MTMR7 contains a N-terminal PH-GRAM domain (
), a Rac-induced recruitment domain (RID) domain, an active Protein Tyrosine Phosphatase (PTP) domain (this entry), a SET-interaction domain, and a C-terminal coiled-coil region.
Myotubularin-related protein 1, protein tyrosine phosphatase domain
Type:
Domain
Description:
MTMR1 (myotubularin-related protein 1) is a lipid phosphatase that uses phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2] as substrates []. MTMR1 is abnormally expressed in myotonic dystrophy type1 (DM1) and in myotonic dystrophy type 2 (DM2), in correlation with muscle pathological features [
].The myotubularin family constitutes a large group of conserved proteins, with 14 members in humans consisting of myotubularin (MTM1) and 13 myotubularin-related proteins (MTMR1-MTMR13). Orthologues have been found throughout the eukaryotic kingdom, but not in bacteria. MTM1 dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) to phosphatidylinositol and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] to phosphatidylinositol 5-monophosphate (PI5P) [,
]. The substrate phosphoinositides (PIs) are known to regulate traffic within the endosomal-lysosomal pathway []. MTMR1, MTMR2, MTMR3, MTMR4, and MTMR6 have also been shown to utilise PI(3)P as a substrate, suggesting that this activity is intrinsic to all active family members. On the other hand, six of the MTM family members encode for catalytically inactive phosphatases. Inactive myotubularin phosphatases contain substitutions in the Cys and Arg residues of the Cys-X5-Arg motif. MTM pseudophosphatases have been found to interact with MTM catalytic phosphatases []. The myotubularin family includes several members mutated in neuromuscular diseases or associated with metabolic syndrome, obesity, and cancer [].This entry represents the active Protein Tyrosine Phosphatase (PTP) domain of MTMR1. This large domain is composed of seven β-strands and sixteen α-helices [
].
This entry consists of several fungal-specific membrane proteins, including Sur7 and Rim9. Sur7 carries four transmembrane domains and is a long-lived component of eisosomes, which are large immobile cell cortex structures associated with endocytosis [
]. It is involved in sporulation [].This entry also includes PalI which is part of a pH signal transduction cascade. Based on the similarity of PalI to the yeast Rim9 meiotic signal transduction component it has been suggested that PalI might be a membrane sensor for ambient pH [
].
This entry represents an uncharacterised domain that is found associated with PF01471, but also a range of lipase and glycosyl hydrolase enzyme domains This suggests this domain may be a regulatory domain.
This family consists of several short, hypothetical bacterial proteins of around 62 residues in length. Members of this family are found in Escherichia coli and Salmonella typhi. The function of this family is unknown.
This is a family of bacterial proteins that have a nucleotidyltransferase fold. The fold-prediction is backed up by conservation of three highly characteristic sequence motifs found in all other nucleotidyl transferases: i) pDhDhhh(h/p), where p is a polar residue and h is a hydrophobic residue; ii) upstream of the first, a GG/S; iii) a conserved D/E in a hydrophobic surround. In the classification of nucleotidyltransferases proposed in [
] this is a group XVIII NTP-transferase. Many of these sequences were classified in the COG database as COG5397. The exact function is not known.
The iron guanylylpyridinol (FeGP) cofactor biosynthesis enzymes are encoded in a cluster of at least seven conserved genes (hcgA-G). This family represents the (SAM)-dependent methyltransferase HgcC [
,
], which covalently attaches the methyl group at the 3-position of the pyridinol ring. It is predominantly found as a monomer in solution, composed of a Rossmann-like coenzyme-binding-domain consisting of six parallel and one peripheral antiparallel strand flanked by six α-helices and a smaller alpha/beta domain.
This family of proteins is functionally uncharacterised. This family of proteins is found in bacteroidetes. Proteins in this family are typically between 329 and 354 amino acids in length.
This family is predominantly composed of bacterial proteins. Their function is unknown, although one family member,
, has been suggested to have a role in maltodextrin utilisation [
].
This entry represents proteins annotated as Ycf55, which are encoded in the chloroplast genomes of algae. Other members are found in plants and in the cyanobacteria. The function is unknown, though there are two completely conserved residues (L and D) that may be functionally important. As the family is exclusively found in phototrophic organisms it may play a role in photosynthesis.
This family of proteins is functionally uncharacterised. This family of proteins is found in proteobacteria. Proteins in this family are typically between 109 and 273 amino acids in length.
Bacillithiol (BSH) functions as a general thiol reductant, analogous to glutathione, in a wide range of bacterial species. Bacilliredoxins reduce those proteins that are modified by disulfide bond formation with BSH (S-bacillithiolation) [
].This entry represents BrxC from Bacillus subtilis (formerly known as YtxJ) and similar bacterial proteins related to BSH. BrxC is a monothiol bacilliredoxin responsible for the removal of BSH from oxidized cytosolic proteins. It can also debacillithiolate the mixed disulfide form of the bacilliredoxin BrxB [
,
]. It has a similar fold to thioredoxin.The homologue in Deinococcus radiodurans, named AbxC, plays a role in the response to oxidative stress [
].
This family of small integral membrane proteins is functionally uncharacterised. This family may be distantly related to
. This family of proteins is predominantly found in proteobacteria. Proteins in this family are typically between 104 and 121 amino acids in length.
The proteins in this entry, which include YgiB, are functionally uncharacterised, however, transcription of ygiB is induced upon biofilm formation compared to planktonic growth in both exponential and stationary phase. Induction of expression was found to be dependent on the presence of the F plasmid [
]. Biofilm formation is impaired in mutants of ygiB [].
Proteins in this entry are functionally uncharacterised. This presumed domain is found in proteins from Alphaproteobacteria. Proteins in this family are typically between 161 and 194 amino acids in length. This family is related to
and is therefore part of the ferritin superfamily.
This entry represents a family of proteins predominantly found in Enterobacterales. Some members in the family are annotated as inner membrane protein YjeO and YgiZ. However no function is currently known.
This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria, archaea and eukaryotes. Proteins in this family are typically between 137 and 165 amino acids in length. Proteins in this family are related to the thiosulfate transporter, but appear to be about half the length. This suggests that this family may operate as a dimer to make a functional transporter.
This presumed domain is functionally uncharacterised. This domain family is found in Planctomycete bacteria, and is approximately 170 amino acids in length.
This family of proteins is functionally uncharacterised. This family of proteins is found in gamma proteobacteria. Proteins in this family are typically between 273 and 287 amino acids in length.
This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria. Proteins in this family are typically between 360 and 412 amino acids in length.
This presumed domain is functionally uncharacterised. This domain is found in eukaryotes. This domain is typically between 350 to 362 amino acids in length. This domain is found C-terminal to
.
This entry represents the C terminus of eukaryotic neogenin precursor proteins, which contains several potential phosphorylation sites [
]. Neogenin is a member of the N-CAM family of cell adhesion molecules (and therefore contains multiple copies of and
) and is closely related to the DCC tumour suppressor gene product - these proteins may play an integral role in regulating differentiation programmes and/or cell migration events within many adult and embryonic tissues [
].
The enzyme in this family is involved in the C2 methylation of bacterial hopanoids. Although the reaction is shown with methylcobalamin acting as the methyl donor, it is possible that SAM might be the methyl donor for the reaction (because this is another function of the SAM cofactor) [
].
Yatakemycin (YTM) is an antitumour natural product. YtkT is a radical S-adenosylmethionine (SAM) protein that when mutated fails to produce YTM. YtkT is a novel C-methyltransferase that contributes to an advanced intermediate during formation of the cyclopropane ring through a radical mechanism in the YTM biosynthetic pathway [
].
OxsB is involved in the biosynthesis of a unique four-membered oxetane ring found in the antiviral agent oxetanocin A. The biosynthetic pathway is currently unknown [
]. OxsB has been identified as a putative radical SAM enzyme.
This family consists of several insect specific haemolymph juvenile hormone binding proteins (JHBP). Juvenile hormone (JH) has a profound effect on insects. It regulates embryogenesis, maintains the status quo of larva development and stimulates reproductive maturation in the adult forms. JH is transported from the sites of its synthesis to target tissues by a haemolymph carrier called juvenile hormone-binding protein (JHBP). JHBP protects the JH molecules from hydrolysis by non-specific esterases present in the insect haemolymph [
]. The crystal structure of the JHBP from Galleria mellonella (Wax moth) shows an unusual fold consisting of a long α-helix wrapped in a much curved antiparallel β-sheet, the so-called TULIP domain []. The folding pattern for this structure closely resembles that found in some tandem-repeat mammalian lipid-binding and bactericidal permeability-increasing proteins, with a similar organisation of the major cavity and a disulphide bond linking the long helix and the β-sheet. It would appear that JHBP forms two cavities, only one of which, the one near the N- and C-termini, binds the hormone; binding induces a conformational change, of unknown significance [,
].Proteins in this entry includes protein Daywake (dyw) and Takeout (to) from fruit flies [
]. Dyw functions in neurons as a day-specific anti-siesta gene, with little effect on sleep levels during the nighttime or in the absence of light []. Protein Takeout is implicated in circadian control of feeding behaviour [,
] and affects male courtship behaviour [].
Bacillus subtilis strain 168 produces the lantibiotic sublancin 168, a broad spectrum bacteriocin. SunI has been identified as the sublancin immunity protein. It belongs to a novel class of bacteriocin antagonists with a particular topology consisting of one N-terminal transmembrane domain and the bulk of the protein facing the cytoplasm [
].
In Drosophila, single-minded (sim) is a transcription factor that acts as the master regulator of neurogenesis. Two mammalian homologues of Sim which have been identified, Sim1 and Sim2, are novel heterodimerisation partners for ARNT in vitro, and may function both as positive and negative transcriptional regulators in vivo, during embryogenesis and in the adult organism [
]. SIM2 is thought to contribute to some specific Down syndrome phenotypes []. There is a high level of homology among mammalian and Drosophila sim proteins in their amino-terminal half where the conserved bHLH, PAS () and PAC motifs are present (
). The PAC region occurs C-terminal to the PAS domains and are proposed to contribute to the PAS domain fold [
,
,
]. In contrast, the carboxy-terminal parts are only conserved in vertebrates []. The Sim1 C terminus contains a Ser-rich region, whereas the Sim2 C terminus both contain Ser/Thr-rich regions, Pro/Ser-rich regions, Pro/Ala-rich regions, and positively charged regions. Sim2s, a splice variant of Sim2, still contains the Ser/Thr- and Pro/Ser-rich regions shown to harbor repressive activities, but is missing the Pro/Ala-rich repressor region [,
,
].
Major Histocompatibility Complex (MHC) glycoproteins are heterodimeric cell surface receptors that function to present antigen peptide fragments to T cells responsible for cell-mediated immune responses. MHC molecules can be subdivided into two groups on the basis of structure and function: class I molecules present intracellular antigen peptide fragments (~10 amino acids) on the surface of the host cells to cytotoxic T cells; class II molecules present exogenously derived antigenic peptides (~15 amino acids) to helper T cells. MHC class I and II molecules are assembled and loaded with their peptide ligands via different mechanisms. However, both present peptide fragments rather than entire proteins to T cells, and are required to mount an immune response.Class I MHC glycoproteins are expressed on the surface of all somatic nucleated cells, with the exception of neurons. MHC class I receptors present peptide antigens that are synthesised in the cytoplasm, which includes self-peptides (presented for self-tolerance) as well as foreign peptides (such as viral proteins). These antigens are generated from degraded protein fragments that are transported to the endoplasmic reticulum by TAP proteins (transporter of antigenic peptides), where they can bind MHC I molecules, before being transported to the cell surface via the Golgi apparatus [
,
]. MHC class I receptors display antigens for recognition by cytotoxic T cells, which have the ability to destroy viral-infected or malignant (surfeit of self-peptides) cells.MHC class I molecules are comprised of two chains: a MHC alpha chain (heavy chain), and a beta2-microglobulin chain (light chain), where only the alpha chain spans the membrane. The alpha chain has three extracellular domains (alpha 1-3, with alpha1 being at the N terminus), a transmembrane region and a C-terminal cytoplasmic tail. The soluble extracellular beta-2 microglobulin chain associates primarily with the alpha-3 domain and is necessary for MHC stability. The alpha1 and alpha2 domains of the alpha chain are referred to as the recognition region, because the peptide antigen binds in a deep groove between these two domains. This entry represents the alpha chain C-terminal tail domain.
This entry represents the NOPS domain and the C-terminal coiled-coil region of PSF (also known as SFPQ). The C-terminal coiled-coil region functions in mediating DBHS dimerization, while some surface-exposed basic residues within the NOPS domain may be involved in nucleic acid binding [
].PSF is a member of the DBHS (Drosophila behavior human splicing) family. It participates in a wide range of gene regulatory processes and cellular response pathways. It has been shown to affect the alternative splicing of CD45 and Tau and regulate the 3' polyadenylation of mRNAs. It is often localised in the paraspeckles and may be involved in the nuclear retention of mRNAs. It is involved in translation and transcription. It can bind directly to DSBs and play a role in DNA repair. PSF can also be utilized as an essential host factor for viral RNA multiplication and replication [
,
]. In addition to the common DHBS core, which encompasses RRM1 and RRM2, the protein-protein interaction NOPS domain and the coiled-coil domain, PSF features additional domains, such as a RGG motif and a proline-rich region in its N terminus []. DBHS (Drosophila behavior human splicing) family are characterised by a core domain arrangement consisting of tandem RNA recognition motifs (RRMs), a conserved intervening sequence referred to as a NONA/ParaSpeckle (NOPS) domain, and a ~100 amino acid coiled-coil domain. Its members include p54nrb (also known as NONO), PTB-associated splicing factor/splicing factor proline-glutamine rich (PSF or SFPQ) and PSPC1 (paraspeckle protein component 1). They are found in the nucleoplasm and can be triggered by binding to local high concentrations of various nucleic acids to form microscopically visible nuclear bodies, paraspeckles or large complexes such as DNA repair foci. They may also function cytoplasmically and on the cell surface in defined cell types. All three DBHS proteins are conserved throughout vertebrate species, while flies, worms, and yeast express a single DBHS protein [
,
].
This family contains Cytidylyl-2-hydroxyethylphosphonate methyltransferase Fom3 which catalyzes the C-methylation of cytidylyl-2-hydroxyethylphosphonate (HEP-CMP) to form cytidylyl-2-hydroxypropylphosphonate (HPP-CMP) [
]. It is involved in fosfomycin biosynthesis [,
,
].
This entry represents the C-terminal of the eukaryotic secreted Golgi casein kinase protein FAM20C. FAM20C is the Golgi casein kinase that phosphorylates secretory pathway proteins within Ser-x-Glu/pSer motifs. Mutations in the FAM20C gene cause Raine syndrome, an autosomal recessive osteosclerotic bone dysplasia [
].
This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria and eukaryotes. Proteins in this family are typically between 342 and 363 amino acids in length.
This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria. Proteins in this family are typically between 102 and 118 amino acids in length.
This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria. Proteins in this family are typically between 188 and 325 amino acids in length.
This family of proteins is functionally uncharacterised. This family of proteins is found in archaea. Proteins in this family are typically between 77 and 127 amino acids in length.
This protein family includes proteins predominantly found in
Gammaproteobacteria, such as YhfG from Escherichia coli. YhfGis a FicA antitoxin homologue (also known as antitoxin EcFicA)
that interacts with EcFiT and forms a complex with it. YhfGshows a unique conformation, forming two parallel α- helices linked by a 10-residues loop. The structure of the complex shows a highly conserved extended ligand-binding
pocket [].
This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria. Proteins in this family are typically between 228 and 260 amino acids in length.
This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria and viruses. Proteins in this family are typically between 216 and 235 amino acids in length.
This family consists of several bacterial proteins of around 150 residues in length which are specific to Escherichia coli, Salmonella species and Yersinia pestis. The function of this family is unknown.
This family of proteins is functionally uncharacterised. This family of proteins is found in firmicutes. Proteins in this family are typically between 258 and 288 amino acids in length.
This family consists of several hypothetical Feline immunodeficiency virus (FIV) proteins. Members of this family are typically around 67 residues long and are often annotated as ORF3 proteins. The function of this family is unknown.
This family of proteins is functionally uncharacterised. This family of proteins is found in cyanobacteria. Proteins in this family are approximately 100 amino acids in length. There is a conserved DQQRWIE sequence motif.
This entry is represented by Bacteriophage P22, Orf80. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria. Proteins in this family are typically between 112 and 148 amino acids in length.
This domain is found at the C-terminal of bacterial regulatory ATPase RavA (Regulatory ATPase variant A)
[
,
]. RavA consists of three domains: the N-terminal domain is the AAA+ module, which is composed of two subdomains, the α-β-alpha subdomain with a Rossmann-type fold commonly found in nucleotide binding proteins and the all-alpha subdomain consisting of four antiparallel α-helices; the second domain is a discontinuous triple-helical domain which has a rigid structure stabilised by hydrophobic interactions localised at the interface between the three helices; and the third domain, named the LARA domain which forms a compact antiparallel β-barrel-like structure consisting of six β-strands and one α-helix [,
]. RavA forms an hexamer in which the triple helical domain mediates the lateral interactions between neighbouring RavA monomers []. This is the second subdomain that forms the discontinuous triple helical domain [
] and contains single completely conserved phenylalanine residue that makes hydrophobic contacts with the AAA+ module resulting in anchoring the triple-helical domain to the AAA+ module. This conserved Phe might serve to transmit the nucleotide-dependent conformational changes in the AAA+ domain to the C-terminal triple-helical and LARA domains of RavA [].
This domain is found at the N terminus of the Gp5 baseplate protein of Bacteriophage T4. The baseplate is located at the end of the phage tail. Gp5 is a lysozyme essential for localised hydrolysis of bacterial cell wall, which is necessary for viral DNA injection [
]. This domain binds to the Gp27 protein []. It has the common OB fold [].
Movement proteins (MPs) encoded by many virus genera are specialised proteins essential for plant viral genomes or virions transport within and between cells. There are some models of virus movement, such as Tobacco mosaic virus (TMV) model or the one described in several families of the icosahedral RNA viruses and pararetroviruses. Aditionally, proteins involved in replication or encapsidation are also required in cell-to-cell movement in some viruses [
].This entry represents the movement protein 6 (p6) from Beet yellows virus and related Closterovirus proteins. P6 is a small protein (6kDa) localised in the endoplasmic reticulum. It has a single-span N-terminal transmembrane domain and a C-terminal hydrophilic domain which faces the cytosol. It is involved, together with Hsp70h, CP, CPm, and P64, in cell to cell movement of the viral genome without any budding, being essential for this process. The mechanism of action of this protein is not clear. It is suggested that it also plays a role in virion formation [
].
The UpxZ family of proteins acts to inhibit transcription of heterologous capsular polysaccharide loci in Bacteroides species by interfering with the action of the UpxY family of transcription anti-terminators. As antagonists of polysaccharide locus-specific UpxY transcription anti-terminators, the UpxZ proteins exert a hierarchical level of regulation, insuring that only one of the multiple phase-variable capsular polysaccharide loci per cell characteristic of this genus is transcribed at a time [
].
This domain is found in several KorB transcriptional repressor proteins. The korB gene is a major regulatory element in the replication and maintenance of broad host-range plasmid RK2. It negatively controls the replication gene trfA, the host-lethal determinants kilA and kilB, and the korA-korB operon [
]. This family is found in conjunction with .
This entry represents a group of major facilitator transporters mostly from fungi, including Str1 from Schizosaccharomyces pombe and Tri12 from Fusarium sporotrichioides. Str1 is involved in the transport of siderophore iron and has a role in iron homeostasis [
]. Tri12 is a trichothecene efflux pump that may play a role in F. sporotrichioides self-protection against trichothecenes [].
This family consists of several Microneme protein Etmic-2 sequences from Eimeria tenella. Etmic-2 is a 50kDa acidic protein, which is found within the microneme organelles of E. tenella sporozoites and merozoites [
].
This entry consists of a number of Caenorhabditis elegans specific repeats of around 36 residues in length which are found in two hypothetical proteins.
This family consists of several bacterial proteins, at least one of which is involved in enzyme induction following nitrogen deprivation. The exact function of this family is unknown
This entry represents the RNA recognition motif 1 (RRM1) of heterogeneous nuclear ribonucleoprotein A3 (hnRNP A3).hnRNP A3 is a novel RNA trafficking response element-binding protein that interacts with the hnRNP A2 response element (A2RE) independently of hnRNP A2 and participates in the trafficking of A2RE-containing RNA. hnRNP A3 can shuttle between the nucleus and the cytoplasm [
]. It contains two RNA recognition motifs (RRMs), followed by a long glycine-rich region at the C terminus.
This entry includes a putative methyltransferase. Shares 24% sequence identity (47% similarity) with fortimycin KL1 methyltransferase (ThnK) from
Micromonospora olivasterospora[
,
].
The enzyme in this family is responsible for the vitamin B12 dependent methylation of the beta-lactam ring in the thienamycin (thn) gene cluster. It is currently not known what the methyl donor is, but in keeping with the other B12-dependent methyltransferases, it is likely to be methylcobalamin, which is regenerated by a second SAM molecule [,
].
This entry represents the C-terminal region of the African swine fever virus (ASFV) IAP-like protein p27. This domain is found in conjunction with
. It has been suggested that the domain may be incoded by the gene involved in aspects of infection in the arthropod host, ticks of the genus Ornithodoros [
].
This entry represents the RNA recognition motif 2 (RRM2) of poly [ADP-ribose] polymerase 14 (PARP-14), also termed aggressive lymphoma protein 2, a member of the B aggressive lymphoma (BAL) family of macrodomain-containing PARPs []. It is expressed in B lymphocytes and interacts with the IL-4-induced transcription factor Stat6. It plays a fundamental role in the regulation of IL-4-induced B-cell protection against apoptosis after irradiation or growth factor withdrawal. It mediates IL-4 effects on the levels of gene products that regulate cell survival, proliferation, and lymphomagenesis. PARP-14 acts as a transcriptional switch for Stat6-dependent gene activation. In the presence of IL-4, PARP-14 activates transcription by facilitating the binding of Stat6 to the promoter and release of HDACs from the promoter with an IL-4 signal. In contrast, in the absence of a signal, PARP-14 acts as a transcriptional repressor by recruiting HDACs []. Absence of PARP-14 protects against Myc-induced developmental block and lymphoma. Thus, PARP-14 may play an important role in Myc-induced oncogenesis []. Additional research indicates that PARP-14 is also a binding partner with phosphoglucose isomerase (PGI)/autocrine motility factor (AMF). It can inhibit PGI/AMF ubiquitination, thus contributing to its stabilization and secretion [].PARP-14 contains two N-terminal RNA recognition motifs (RRMs), three tandem macro domains, and C-terminal region with sequence homology to PARP catalytic domain.
This family consists of several mammalian specific BCL2/adenovirus E1B 19kDa protein-interacting protein 3 or BNIP3 sequences. BNIP3 belongs to the Bcl-2 homology 3 (BH3)-only family, a Bcl-2-related family possessing an atypical Bcl-2 homology 3 (BH3) domain, which regulates PCD from mitochondrial sites by selective Bcl-2/Bcl-XL interactions. BNIP3 family members contain a C-terminal transmembrane domain that is required for their mitochondrial localisation, homodimerisation, as well as regulation of their pro-apoptotic activities. BNIP3-mediated apoptosis has been reported to be independent of caspase activation and cytochrome c release and is characterised by early plasma membrane and mitochondrial damage, prior to the appearance of chromatin condensation or DNA fragmentation [
].
Radical SAM domain protein TunB is involved in the biosynthesis of tunicamycins. It catalyses the radical coupling reaction in which a 5'-uridyl radical undergoes radical addition at C6 of N-acetyl-galactoseamine-5,6-ene to yield an alpha-alkoxyalkyl radical. Subsequent hydrogen atom abstraction from 5'-deoxyadenosine could lead to UDP-N-acetyl-tunicamine-uracil and the regeneration of SAM [].
This family represents a conserved region within Agrobacterium tumefaciens VirE3. Agrobacterium tumefaciens (a plant pathogen) has a tumour-inducing (Ti) plasmid of which part, the transfer (T)-region, is transferred to plant cells during the infection process. Vir proteins mediate the processing of the T-region and the transfer of a single-stranded (ss) DNA copy of this region, the T-strand, into the recipient cells. VirE3 is a translocated effector protein, but its specific role has not been established [
].
Protein wntless (Wls) regulates Wnt proteins sorting and secretion in a feedback regulatory mechanism [
,
,
]. This reciprocal interaction plays a key role in the regulation of expression, subcellular location, binding and organelle-specific association of Wnt proteins. It also plays also an important role in establishment of the anterior-posterior body axis formation during development [].
This family contains a group of hypothetical bacterial proteins that contain three conserved cysteine residues towards the N-terminal. The function of these proteins is unknown.
This family consists of several bacterial phage shock protein B (PspB) sequences. The phage shock protein (psp) operon is induced in response to heat, ethanol, osmotic shock and infection by filamentous bacteriophages [
]. Expression of the operon requires the alternative sigma factor sigma54 and the transcriptional activator PspF. In addition, PspA plays a negative regulatory role, and the integral-membrane proteins PspB and PspC play a positive one [].
This domain is found in RNA-directed RNA polymerase L from Bunyavirales. This has been described as the PA-C like domain, which forms a narrow and positively charged cleft with the thumb domain, where the 3' RNA is likely bound [
].
Complex IV (CIV) is a copper-heme oxidase that couples electron transfer from cytochrome c to oxygen with proton extrusion across the inner membrane to contribute to the proton gradient required for ATP generation. This entry includes fungal mitochondrial complex IV assembly factor Cox20 [
] and its homologues (also known as (FAM36A) in metazoa [].Human CIV is formed by three catalytic core subunits (COX1/2/3). COX20 has been found to form a complex with SCO1, SCO2, and newly synthesized COX2. It may act as a chaperone in the early steps of COX2 maturation [
].
This is a family of exported virulence proteins from largely Acinetobacteria and a few Fimicutes, Gram-positive bacteria. It is exported in conjunction with EspA as an interacting pair [
,
,
].
This domain occurs C-terminal to phosphoribosyl transferase domain
, and has a highly conserved GXXE and TRSP signatures [
]. It is found in bacteria. These genes are found in the biosynthetic operon associated with the Ter stress response operon and are predicted to be involved in the biosynthesis of a ribo- nucleoside involved in stress response [].
This region is found in viruses, and is approximately 20 amino acids in length. The region is found C-terminal to
. There is a single completely conserved residue Y that may be functionally important.
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 entry includes a group of transmembrane proteins, including CmpB from bacteria and TMEM229 from animals. CmpB is a family of membrane proteins that are likely to be part of a two-component type IV ABC-transporter system. Families can transport multiple drugs including ethidium and fluoroquinolones. UniProtKB:Q83XH0 (
) is a member of TCDB family [
].
SARAF is an endoplasmic reticulum membrane resident protein that serves as a negative regulator of store-operated Ca2+ entry (SOCE) involved in protecting cells from Ca2+ overfilling. It is a single pass ER membrane protein whose systolic-facing domain is responsible for activity and whose luminary-facing domain carries out a regulatory function in conjunction with another membrane protein STIM, an ER single pass membrane protein that detects changes in ER Ca2+ levels through its EF-hand, conserved Ca2+ binding domain. STIM is the major target for SARAF regulation, and thus SARAF negatively regulates the SOCE entry of calcium into cells protecting them from overfilling [
].
