There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. However, they are found in an operon along with components of a TonB transport system (typified by Vibrio cholerae TonB2 [
], and are predicted to be localized to the periplasmic space.Caution: the low-complexity nature of these sequences produces spurious BLAST hits to chromosome segregation ATPases (which are much longer in length and contain canonical Walker motifs). Accordingly, some members are misidentified as such.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
The mercury resistance protein, MerC, is an inner membrane protein that mediates Hg
2+transport into the cytoplasm [
,
]. MerA then converts the inorganic form of mercury Hg2+ to the less toxic form Hg0, thereby conferring mercury resistance [].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Nitrogenase is a complex metalloenzyme composed of two proteins designated the Fe-protein and the MoFe-protein. Apart from
these two proteins, a number of accessory proteins are essential for the maturation and assembly of nitrogenase. Even thoughexperimental evidence suggests that these accessory proteins are required for nitrogenase activity, the exact roles played by many of
these proteins in the functions of nitrogenase are unclear []. Using yeast two-hybrid screening it has been shown that NifW caninteract with itself as well as NifZ.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. However, several members are predicted to have a membrane lipoprotein lipid attachment site. In addition, there are several stringently conserved glutamine residues.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Proteins in this entry are required for type I protein secretion and have an N-terminal ABC transporter type 1 transmembrane domain and a C-terminal P-loop containing nucleoside triphosphate hydrolase domain. The transmembrane domain forms a pore in the inner membrane and the ATP-binding domain is responsible for energy generation. Sequences are mainly from bacteria, but there are homologues from eukaryotes and archaea. Proteins in this entry include the following:
Lipid A export ATP-binding/permease protein MsbA, which is required for lipid A and possibly glycerophospholipid transport, and for biogenesis of the outer membrane in bacteria [
]
Beta-(1-->2)glucan export ATP-binding/permease protein NdvA from nitrogen-fixing bacteria, which is required for beta-(1-->2)glucan export, essential for nodule formation in legume roots [
]
Iron-sulfur clusters transporter ATM1, a yeast mitochondrial protein that exports Fe/S cluster-containing protein precursors and other mitochondrially synthesized proteins to the cytoplasm [
]. The mammalian equivalents are the ATP-binding cassette sub-family B members 6, 7, 8 and 9, which are required for the transport of heme and porphyrin from the cytoplasm to the mitochondrion []
Leukotoxin translocation ATP-binding protein LktB, required for leukotoxin export in
Mannheimia haemolyticaMultidrug resistance protein 1, which exports xenobiotics, such as cytotoxic drugs, out of cells leading to tumour cell resistance to multiple drugs [
]. The bacterial equivalents include multidrug resistance-like ATP-binding protein MdlAAlpha-hemolysin translocation ATP-binding protein HlyB from
E. coli, a component of the ABC transporter complex HlyBD required for the export of hemolysin [
]
Phosphatidylcholine translocator ABCB4, required for lipid secretion in the bile, transporting phosphatidylcholine from the inner to the outer leaflet of the canalicular membrane bilayer into the canaliculi of hepatocytes [
]
Bile salt export pump, required for the secretion of bile salts into the canaliculus of hepatocytes [
]
Antigen peptide transporter 1, which is required for the transport of antigens from the cytoplasm to the endoplasmic reticulum for association with MHC class I molecules [
]
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. However, they possess a predicted signal peptide.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
The only essential histone acetyltransferase complex in Saccharomyces cerevisiae, NuA4, acetylates the N-terminal tails of histones H4 and H2A. Experimental analyses have revealed at least two functionally distinct polypeptide groups in NuA4: Vid21/Yng2 and Eaf5/Eaf7. While the former are required for bulk histone H4 acetylation and are functionally linked to the histone H2A variant Htz1 and the Swr1 ATPase complex (SWR-C) that assembles Htz1 into chromatin, Eaf5 and Eaf7 have an, as yet, undefined role. It is thought that a NuA4/SWR-C/Htz1 pathway may regulate both transcription and centromere function in S.cerevisiae [
].
In Saccharomyces cerevisiae, daughter-specific genetic programs induce distinct fates for mother and daughter cells. Some daughter-specific gene products have been shown to contribute to cell separation by degrading the cell wall [
]. A group of these genes (including ENG1, SCW11, DSE1 and DSE2) are regulated by the transcription factor Ace2p [].More specifically, the DSE2 gene has been shown to encode a secreted protein with sequence similarity to glucanases. It is believed that this protein contributes to the degradation of the cell wall from the daughter side, causing daughter cells to separate from mother cells [
].
Bacteriophage lambda encodes two repressors: the Cro repressor that acts to turn off early gene transcription during the lytic cycle, and the lambda or cI repressor that is required to maintain lysogenic growth. Together the Cro and cI repressors form a helix-turn-helix (HTH) superfamily. The lambda Cro repressor binds to DNA as a highly flexible dimer. The crystal structure of the lambda Cro repressor [
] reveals a HTH DNA-binding protein with an alpha/beta fold that differs from other Cro family members, possibly by an evolutionary fold change []. Most Cro proteins, such as Enterobacteria phage P22 Cro and Bacteriophage 434 Cro, have an all-alpha structure that is thought to be ancestral to lambda Cro, where the fourth and fifth helices are replaced by a β-sheet, possibly as a result of secondary structure switching rather than by nonhomologous replacement []. This entry represents the lambda-type Cro repressor with an alpha/beta topology.
Members of this entry, which includes the Bacillus subtilis protein YsxE, are found only in the family Bacillaceae, part of the the endospore-forming group within the Firmicutes. As a rule, the ysxE gene is found immediately downstream of spoVID, a gene necessary for spore coat assembly. The protein has been shown to be part of the spore coat and is a homologue of CotS (
).
This entry represents a group of proteins mainly from an endospore-forming group within firmicutes, including Spore coat protein S/I (COTS/I), Endospore coat-associated protein YutH and Uncharacterized protein YsxE from Bacillus subtilis. YutH has been shown to be involved in spore coat assmebly [
].
This entry, represented by the Bacillus subtilis protein YutH, is found only in the family Bacillaceae, part of the endospore-forming group within the Firmicutes. YutH has been shown to be involved in spore coat assmebly [
]. Proteins in this entry are homologous to CotS ().
Members of this entry include the spore coat proteins CotS and YtaA from Bacillus subtilis and, from other endospore-forming bacteria, homologues that are more closely related to these two than to the spore coat proteins YutH (
) and YsxE (
). The CotS family is more broadly distributed than YutH or YsxE, but still is not universal among spore-formers.
The Rnd proteins, which form a distinct sub-group of the Rho family of small GTP-binding proteins, have been shown to regulate the organization of the actin cytoskeleton in several tissues [
]. This entry represents RhoE (also known as Rnd3 or Rho8), which is a member of the Rnd subfamily. Unlike other small G proteins, RhoE, along with two other proteins Rnd1/Rho6 and Rnd2/RhoN, does not hydrolyze GTP []. This is due to changes in key amino acids involved in catalysing GTP hydrolysis []. RhoE is known to bind the serine-threonine kinase ROCK I. Unphosphorylated RhoE associates primarily with membranes, but ROCK I-phosphorylated RhoE localizes in the cytosol [
]. Phosphorylation of RhoE correlates with its activity in disrupting RhoA-induced stress fibres and inhibiting Ras-induced fibroblast transformation []. In mammary epithelial tumor cells, RhoE regulates the assembly of the apical junction complex and tight junction formation []. In cells that lack stress fibres, such as macrophages and monocytes, RhoE induces a redistribution of actin, causing morphological changes in the cell []. In addition, RhoE has been shown to inhibit cell cycle progression in G1 phase at a point upstream of the pRb family pocket protein checkpoint []. RhoE has also been shown to inhibit Ras- and Raf-induced fibroblast transformation. RhoE is underexpressed in prostate cancer cells both in vitro and in vivo; re-expression of RhoE suppresses cell cycle progression and increases apoptosis, suggesting it may play a role in tumor suppression [].
The Rnd proteins, which form a distinct sub-group of the Rho family of small GTP-binding proteins, have been shown to regulate the organization of the actin cytoskeleton in several tissues [
]. RhoN (also known as Rnd2 or Rho7) is a member of the novel Rho subfamily Rnd, together with Rnd1/Rho6 and Rnd3/RhoE/Rho8. Unlike other small G proteins, Rnd2/RhoN, Rnd3/RhoE, and Rnd1/Rho6 and do not hydrolyze GTP []. This is due to changes in key amino acids involved in catalysing GTP hydrolysis [].Rnd2/RhoN is transiently expressed in radially migrating cells in the brain while they are within the subventricular zone of the hippocampus and cerebral cortex. These migrating cells typically develop into pyramidal neurons. Cells that exogenously expressed Rnd2/RhoN failed to migrate to upper layers of the brain, suggesting that Rnd2/RhoN plays a role in the radial migration and morphological changes of developing pyramidal neurons, and that Rnd2/RhoN degradation is necessary for proper cellular migration. The Rnd2/RhoN GEF Rapostlin is found primarily in the brain and together with Rnd2/RhoN induces dendrite branching [,
]. Unlike Rnd1/Rho6 and Rnd3/RhoE/Rho8, which are RhoA antagonists, Rnd2/RhoN binds the GEF Pragmin and significantly stimulates RhoA activity and Rho-A mediated cell contraction []. Rnd2/RhoN is also found to be expressed in spermatocytes and early spermatids, with male-germ-cell Rac GTPase-activating protein (MgcRacGAP), where it localizes to the Golgi-derived pro-acrosomal vesicle [].
The 78kDa centrosomal proteins are thought to aid the centrosome structure by helping to form microtubules, although this has yet to be been fully confirmed [
]. Their sequences are believed to contain 3 leucine-rich (LRR) repeats, and a potential coiled-coil region towards the C terminus, but the functionality conferred on the proteins by the possession of these domains is currently unknown [].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. They are closely related to the N-terminal portion of a KpnI-like type III restriction-modification system methyltransferase in Mycoplasmas (
). However, they lack the conserved catalytic motifs [
].
Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins [
,
]. On the basis of sequence similarities, the vast majority of these solute-binding proteins can be grouped [
] into eight families or clusters, which generally correlate with the nature of the solute bound. Family 5 members include:Periplasmic oligopeptide-binding proteins (oppA) of Gram-negative bacteria and homologous lipoproteins in Gram-positive bacteria (oppA, amiA or appA)Periplasmic dipeptide-binding proteins of Escherichia coli (dppA) and Bacillus subtilis (dppE)Periplasmic murein peptide-binding protein of E. coli (mppA) Periplasmic peptide-binding proteins sapA of E. coli, Salmonella typhimurium and Haemophilus influenzaePeriplasmic nickel-binding protein (nikA) of E. coliHaem-binding lipoprotein (hbpA or dppA) from H. influenzaeLipoprotein xP55 from Streptomyces lividansHypothetical proteins from H. influenzae (HI0213) and Rhizobium sp. (strain NGR234) symbiotic plasmid (y4tO and y4wM)HTH-type transcriptional regulator SgrR from E. coli. The solute-binding domain is localised in its C-terminal [
].
This family includes transport proteins such as sodium-lithium/proton antiporter from Halobacillus [
] and sporulation protein YtvI from Bacillus subtilis, a putative permease []. YtvI has extensive hydrophobic regions and is likely to be an integral membrane protein.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.This entry represents a family of proteins from bacteria whose function is unknown. Most members contain the domain
, conserved in glycoamylases.
This group represents uncharacterised conserved proteins. The domain contained within these proteins (
) is found in various proteins known to bind RNA. These include Mycoplasma pulmonis cysteinyl-tRNA synthetase (some members are misannotated as such) and FAU-1 [
] (). However, the RNA binding region does not map to this domain, and thus the function of the domain remains unclear. Interestingly, this domain is also found in an uncharacterised protein (FomD) of the fosfomycin synthesis cluster in Streptomyces wedmorensis [
].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Arl6 (Arf-like 6) forms a subfamily of the Arf family of small GTPases. Arl6 expression is limited to the brain and kidney in adult mice, but it is expressed in the neural plate and somites during embryogenesis, suggesting a possible role for Arl6 in early development [
]. Arl6 is also believed to have a role in cilia or flagella function. Several proteins have been identified that bind Arl6, including Arl6 interacting protein (Arl6i), and SEC61beta, a subunit of the heterotrimeric conducting channel SEC61 []. Based on Arl6 binding to these effectors, Arl6 is also proposed to play a role in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation []. At least three specific homozygous Arl6 mutations in humans have been found to cause Bardet-Biedl syndrome, a disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism [,
]. Older literature suggests that Arl6 is a part of the Arl4/Arl7 subfamily, but analyses based on more recent sequence data place Arl6 in its own subfamily.
Centrosomal protein of 290kDa (Cep290) is part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition. It activates ATF4-mediated transcription. It is required for the correct localisation of ciliary and phototransduction proteins in retinal photoreceptor cells and may play a role in ciliary transport processes [
,
,
].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Members of this entry are found in a subset of nitrogen-fixing bacteria and are annotated as nitrogen fixation protein NifM. NifM is homologous to peptidyl-prolyl cis-trans isomerases and appears to be an accessory protein for NifH, the Fe protein, also called component II or dinitrogenase reductase, of nitrogenase [
].
Members of this protein family are small bacterial proteins, each with an N-terminal signal sequence followed by up to 11 imperfect repeats of a pentapeptide. The pentapeptide repeat is usually of the form Met-Xaa-Lys-Asp-Xaa. Family member methionine-rich peptide X, from Dechlorosoma suillum, has been shown to serve as an oxidative stress sink, specifically for chlorite and hypochlorite [
].
This entry represents the SAM pointed domain of protein C-ets-1 (also known as ETS-1), which is an ETS transcriptional activator. The SAM pointed domain is a protein-protein interaction domain. The ETS-1 activator is regulated by phosphorylation. It contains a docking site for the ERK2 MAP (Mitogen Activated Protein) kinase, while the ERK2 phosphorylation site is located in the N-terminal disordered region upstream of the SAM Pointed domain. Mutations of the kinase docking site residues inhibit phosphorylation [
,
]. ETS-1 activators play a role in a number of different physiological processes, and they are expressed during embryonic development, including blood vessel formation, hematopoietic, lymphoid, neuronal and osteogenic differentiation []. The Ets-1 gene is a proto-oncogene involved in progression of different tumors (including breast cancer, meningioma, and prostate cancer). ETS-1 is a potential molecular target for selective cancer therapy [].
Found in the main part of the sperm flagellum, the fibrous sheath is a cytoskeletal structure comprising two longitudinal columns connected by closely spaced circumferential ribs [
]. A-kinase anchoring proteins (AKAPs) secure cyclic AMP-dependent protein kinases within specific cytoplasmic domains; most abundant in the fibrous sheath is AKAP4 []. AKAP4 has been shown to bind AKAP3 and two spermatogenic cell-specific proteins, Fibrous Sheath Interacting Proteins 1 and 2 (FSIP1, FSIP2) [].How the fibrous sheath assembles is not yet fully understood. AKAP4 is synthesised and incorporated into the nascent fibrous sheath late in spermatid development; its precursor is processed in the flagellum, and only the mature form of AKAP4 appears to bind AKAP3 [
]. It is likely, therefore, that AKAP3 is involved in organising the basic structure of the fibrous sheath, while AKAP4 helps to complete fibrous sheath assembly.The FSIP1 protein is 435 amino acids in length, and is rich in glutamine and asparagine [
]. Minimum domains for its binding to AKAP4 have been localised to amino acids 351-359 and 692-721 of AKAP4 constructs [].
This entry contains carbonic anhydrase related proteins (CARPs) X and XI, which have been implicated in various biological processes of the central nervous system. CARPs are sequence similar to carbonic anhydrases. Carbonic anhydrases are zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide in a two-step mechanism. CARPs have lost conserved histidines involved in zinc binding and consequently their catalytic activity [
]. CARP XI plays a role in the development of gastrointestinal stromal tumors []. Phylogeny shows that CARP XI emerged from CARP X [].
Carbonic anhydrase related proteins (CARPs) are sequence similar to carbonic anhydrases. Carbonic anhydrases are zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide in a two-step mechanism. CARPs have lost conserved histidines involved in zinc binding and consequently their catalytic activity [
,
]. CARP VIII may play roles in various biological processes of the central nervous system and is associated with motor coordination [,
,
]. CARP VIII has been shown to bind inositol 1,4,5-triphosphate (IP3) receptor type I (IP3RI), reducing the affinity of the receptor for IP3. IP3RI is an intracellular IP3-gated Ca2+ channel located on intracellular Ca2+ stores. IP3RI converts IP3 signaling into Ca2+ signaling thereby participating in a variety of cell functions []. CARP VIII has been linked to neurodegeneration and development of colorectal and lung cancers in humans [].Carbonic anhydrases (CA:
) are zinc metalloenzymes which catalyse the reversible hydration of carbon dioxide to bicarbonate [
,
]. CAs have essential roles in facilitating the transport of carbon dioxide and protons in the intracellular space, across biological membranes and in the layers of the extracellular space; they are also involved in many other processes, from respiration and photosynthesis in eukaryotes to cyanate degradation in prokaryotes. There are five known evolutionarily distinct CA families (alpha, beta, gamma, delta and epsilon) that have no significant sequence identity and have structurally distinct overall folds. Some CAs are membrane-bound, while others act in the cytosol; there are several related proteins that lack enzymatic activity. The active site of alpha-CAs is well described, consisting of a zinc ion coordinated through 3 histidine residues and a water molecule/hydroxide ion that acts as a potent nucleophile. The enzyme employs a two-step mechanism: in the first step, there is a nucleophilic attack of a zinc-bound hydroxide ion on carbon dioxide; in the second step, the active site is regenerated by the ionisation of the zinc-bound water molecule and the removal of a proton from the active site [
]. Beta- and gamma-CAs also employ a zinc hydroxide mechanism, although at least some beta-class enzymes do not have water directly coordinated to the metal ion. The alpha-CAs are found predominantly in animals but also in bacteria and green algae. There are at least 15 isoforms found in mammals, which can be subdivided into cytosolic CAs (CA-I, CA-II, CA-III, CA-VII and CA XIII), mitochondrial CAs (CA-VA and CA-VB), secreted CAs (CA-VI), membrane-associated (CA-IV, CA-IX, CA-XII and CA-XIV) and those without CA activity, the CA-related proteins (CA-RP VIII, X and XI).The beta-CAs are highly abundant in plants, diatoms, eubacteria and archaea [
,
]. The beta-CAs are far more diverse in sequence than other classes, and can be divided into different clades based on sequence identity, with the plant enzymes forming two clades representing dicotyledonous and monocotyledonous plants. Characterisation of these enzymes reveals sharp differences between the beta class, which forms dimers, tetramers, hexamers and octomers, and the alpha and gamma classes, which form strictly monomers and trimers. The gamma-CAs may be the most ancient form of carbonic anhydrases, having evolved long before the alpha class, to which it is more closely related than to the beta-class [
,
]. The reaction mechanism of the gamma-class is similar to that of the alpha-class, even though the overall folds are dissimilar and the active site residues differ. The delta-CAs are found in marine algae and dinoflagellates [
]. The epsilon-CAs are found in prokaryotes such as Thiobacillus neapolitanus (Halothiobacillus neapolitanus) in which it is a component of the carboxysome shell, where it could supply the active sites of RuBisCO in the carboxysome with the high concentrations of carbon dioxide necessary for optimal RuBisCO activity and efficient carbon fixation [
].
Two members of this family are found in Colwellia psychrerythraea (strain 34H / ATCC BAA-681) and one each in various other species of Colwellia and Shewanella. One member from C. psychrerythraea is of special interest because it is preceded by the same cis-regulatory site as a number of genes that have the PEP-CTERM domain described by
.
Members of this protein family, found in three different species so far, have a PEP-CTERM sequence at the carboxyl-terminus (
), but are unusual among PEP-CTERM proteins in having multiple predicted transmembrane segments. The function is unknown. It is proposed that a member of the EpsH family, to be designated exosortase (see
), recognises and cleaves PEP-CTERM proteins in a manner analogous to the cleavage of LPXTG proteins by sortase [
].
This entry includes the T6S-associated protein, TagF, a post-translational repressor of the hemolysin co-regulated secretion island I (HSI-I)-encoded type VI secretion system (H1-T6SS), found in Pseudomonas aeruginosa. The type VI secretion system (T6SS) is found broadly among the Proteobacteria and is implicated in diverse processes including host-cell interactions, biofilm formation and gene regulation. Furthermore, studies indicate that the T6SS plays a critical role in interbacterial interactions. TagF has been shown to regulate the activity of the H1-T6SS in a manner that does not require phosphorylated-Fha1, PpkA, or other Tag proteins. TagF forms a homodimer with nearly identical monomers composed of alpha and beta elements assembled as a three-layer sandwich (α-β-alpha) [
].
DMP12 is a DNA-mimic protein from Neisseria species. In its monomeric form DMP12 interacts with the Neisseria dimeric form of the bacterial histone-like protein HU. HU proteins promote the assembly of higher-order DNA-protein structures. The interaction between DMP12 and HU may be instrumental in controlling the stability of the nucleoid in Neisseria, as DMP12 prevents Neisseria HU protein from being digested by trypsin [
].
The THAP domain is a C2CH module with zinc-dependent sequence-specific DNA-binding activity [
]. Several THAP domain-containing proteins have been described. Human THAP1 is a transcription regulator that regulates endothelial cell proliferation and G1/S cell-cycle progression []. It specifically binds the 5'-[AT]NTNN[GT]GGCA[AGT]-3' core DNA sequence and acts by modulating expression of pRB-E2F cell-cycle target genes, including RRM1. It is a component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. It may also have pro-apoptopic activity by potentiating both serum-withdrawal and TNF-induced apoptosis [
,
,
]. Defects in THAP1 are the cause of dystonia type 6 (DYT6). DYT6 is a primary torsion dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Dystonia type 6 is characterised by onset in early adulthood, cranial or cervical involvement in about half of the cases, and frequent progression to involve multiple body regions [
,
,
,
]. This entry also includes THAP10, whose function is clear.
The THAP domain is a C2CH module with zinc-dependent sequence-specific DNA-binding activity [
]. Several THAP domain-containing proteins have been described. THAP7 is a chromatin-associated, histone tail-binding protein that represses transcription via recruitment of histone deacetylase 3 (HDAC3) and nuclear hormone receptor corepressors (NCoR) [].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
The proteins in this family are functionally uncharacterised. The proteins are around 450 amino acids long and includes Streptococcus pneumoniae Sp0239 (
) and similar uncharacterized proteins. Sp0239 is structurally similar to ribonucleotide reductase (RNR) and pyruvate formate lyase (PFL), which are believed to have diverged from a common ancestor. RNR and PFL possess a ten-stranded α/β barrel domain that hosts the active site, and are radical enzymes. RNRs are found in all organisms and provide the only mechanism by which nucleotides are converted to deoxynucleotides. PFL is an essential enzyme in anaerobic bacteria that catalyses the conversion of pyruvate and CoA to acteylCoA and formate.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. However, they are predicted to be integral membrane proteins, with several transmembrane segments.
ZntB is integral membrane protein consisting largely of two independent domains. The first 266 amino acids form a large, highly charged
domain within the cytoplasm, while the remaining 61 residues form a small membrane domain containing two membrane-spanning segments []. ZntB mediates efflux of zinc ions [].
In general, proteins from the MATE family are involved in exporting metabolites across the cell membrane and are often responsible for multidrug resistance (MDR) [
,
]. These proteins mediate resistance to a wide range of cationic dyes, fluroquinolones, aminoglycosides and other structurally diverse antibodies and drugs. MATE proteins are found in bacteria, archaea and eukaryotes. These proteins are predicted to have 12 α-helical transmembrane regions, some of the animal proteins may have an additional C-terminal helix []. This entry represents the multidrug resistance protein MdtK subfamily.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
The X-domain, a macrodomain, is found in riboviral non-structural protein 3 (NSP3), including the NSP3 of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and other coronaviruses (alpha-, beta-, gamma-, and deltacoronavirus), among others. The SARS-CoV X-domain may function as a module binding poly(ADP-ribose), a metabolic product of NAD+ synthesized by poly(ADP-ribose) polymerase (PARP) [
]. The X-domain of Avian infectious bronchitis virus (IBV) strain Beaudette coronavirus does not bind ADP-ribose; the triple glycine sequence found in the X-domains of SARS-CoV and human coronavirus 229E (HCoV229E), which are involved in ADP-ribose binding, is not conserved in the IBV X-domain. SARS-CoV has two other macrodomains referred to as the SUD-N (N-terminal subdomain) and SUD-M (middle SUD subdomain) of the SARS-unique domain (SUD), which also do not bind ADP-ribose; these bind G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides) [].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Formyl Peptide Receptor-Like 1 (FPRL1)-inhibitory protein (also termed FLIPr) has been shown to inhibit calcium mobilisation in neutrophils [
]. There is evidence that FLIPr binds to FPRL1 and, at higher concentrations, to FPR [], impairing the leukocyte response to FPRL1 agonists. It has revealed unknown inflammatory ligands during S.aureus infection and, as an FPRL1 antagonist, may facilitate development of therapeutic agents in FPRL1-mediated inflammatory diseases [].Chemotaxis inhibitory protein (also knows as CHIPS) is a Staphylococcus aureus-secreted virulence factor that impairs the response of neutrophils and monocytes to FPR and C5a [
]. CHIPS has been shown to reduce neutrophil recruitment toward C5a in mouse models (its activity is more potent on human than on mouse cells). As such, its properties may make it a candidate new anti-inflammatory therapeutic compound [].CHIPS also plays an key role in bacterial invasion, by inhibiting FMLP- and C5a-induced calcium moblisation [
]. By influencing 2 related receptors with very different ligand specificities (C5aR and FPR), the protein has a unique role; nevertheless, neither the manner in which it binds such structurally different molecules nor how its expression is regulated are currently unknown [].The structure of a CHIPS fragment (residues 31-121) has been solved by NMR spectroscopy [
]. This fragment has the same activity in blocking the C5aR relative to full-length CHIPS, but lacks FPR antagonism []. The protein has a compact fold comprising 2 short α-helices packed onto a 4-stranded anti-parallel β-sheet: strands-2 and -3 are joined by a loop with a well-defined conformation []. The protein shares a high degree of structural similarity with a number of proteins, including the C-terminal domain of staphylococcal superantigen-like proteins (SSLs) 5 and 7, staphyloccocal and streptococcal superantigens TSST-1 and SPE-C, and various domains of the staphylococcal extracellullar adherence protein (EAP) [].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Ribosomal protein L22e forms part of the 60S ribosomal subunit [
] found in eukaryotes. Rattus norvegicus (Rat) L22 is related to ribosomal proteins from other eukaryotes and is identical in amino acid sequence to human EAP, the EBER 1 (Epstein-Barr virus (strain GD1) (HHV-4) (Human herpesvirus 4) encoded RNA) associated protein [].
There is currently no experimental data for members of this group of proteins or their homologues, nor do they exhibit features indicative of any function. However, they are predicted to be membrane proteins.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
This family of carlavirus nucleic acid binding proteins includes a motif for a potential C-4 type zinc finger this has four highly conserved cysteine residues and is a conserved feature of the carlaviruses 3' terminal ORF [
]. These proteins may function as viral transcriptional regulators. The carlavirus family includes Garlic latent virus and Potato virus S and Potato virus M, these viruses are positive strand, ssRNA with no DNA stage.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
The THAP domain is a C2CH module with zinc-dependent sequence-specific DNA-binding activity [
]. Several THAP domain-containing proteins have been described. This entry represents THAP domain-containing protein 2 (THAP2).
The THAP domain is a C2CH module with zinc-dependent sequence-specific DNA-binding activity [
]. Several THAP domain-containing proteins have been described. THAP3 is a component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of the cell cycle-specific gene RRM1 [].
Coiled-coil domain-containing protein 8 (CCDC8) is a widely expressed protein [
]. It is phosphorylated upon DNA damage, probably by ATM or ATR [,
]. It is a core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer [
,
]. CCDC8 is also required for localization of CUL7 to the centrosome [].Defects in CCDC8 are the cause of 3M syndrome type 3 (3M3), a disorder characterised by poor postnatal growth and distinctive facial features, including triangular facies, frontal bossing, fleshy tipped nose, and fleshy lips. Other features may include skeletal anomalies and prominent heels [
].
This entry consists of antitermination proteins found in bacteriophages, such as protein Q from phage lambda, and some bacterial homologues. Protein Q positively regulates expression of the phage late gene operon by binding to the bacterial host RNA polymerase (RNAP) and modifying it. This protein binds a specific DNA Q-binding element (QBE) and interacts with RNAP. The modified RNAP can read without pausing and through transcription terminators preceding late genes [
,
]. It participates in the lysis-lysogeny decision by activating the expression of the late lytic genes []. The structure of Q from bacteriophage 21 revealed that it forms a torus, that narrows and extends the RNAP RNA-exit channel and extrudes the linked RNA, preventing the formation of pause and terminator hairpins [].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. A number of eukaryotic ribosomal proteins can be grouped on the basis of
sequence similarities. These proteins have 82 to 87 amino acids. The amino termini are all N alpha-acetylated. The N-terminal halves of the protein molecules are highly conserved in contrast to the carboxy-terminal parts [].This entry represents the ribosomal protein S21 (RpS21). It bounds to native 40S ribosomal subunits in a salt-labile association and is absent from polysomes, indicating that it acts as a translation initiation factor rather than as a core ribosomal protein [
].
Proteins in this family include T-complex protein 10 and centromere protein J (CENPJ). T-complex is involved in spermatogenesis in mice [
]. T-complex protein 10A homologue 2 (also known as TCP10L) may be involved in transcriptional regulation and has in vitro transcription inhibition activity []. It acts as a tumour suppressor in hepatocellular carcinoma (HCC) cells []. CENPJ not only inhibits microtubule nucleation from the centrosome, but also depolymerises taxol-stabilised microtubules [,
,
].
DivIB is a cell division protein from Gram-positive bacteria, probably homologous to Escherichia coli FtsQ. DivIB interacts with FtsL, DivIC and PBP-2B [
,
]. DivIB plays an essential role in division at high temperatures, maybe by protecting FtsL from degradation or by promoting formation of the FtsL-DivIC complex []. It is also required for efficient sporulation at all temperatures [].
This family represents the cell division protein FtsP that is required for growth during stress conditions. FtsP may be involved in protecting or stabilising the divisomal assembly under conditions of stress [
].
FtsQ is an essential cell division protein. It may link together the upstream cell division proteins, which are predominantly cytoplasmic, with the downstream cell division proteins, which are predominantly periplasmic [
]. FtsQ may control the correct divisome assembly [].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
A number of eukaryotic ribosomal proteins can be grouped on the basis of sequence similarities. One
of these families, the S26E family, includes mammalian S26 []; Octopus S26 [];Drosophila S26 (DS31) [
]; plant cytoplasmic S26; and fungal S26 []. S26 may be involved in the attachment of eIF3 and poly (U) []. Disruption of RPS26, the gene encoding a homologue of ribosomal protein small subunit S26 in yeast (S. cerevisiae), resulted in the formation of micro-colonies, suggesting that it is important for the normal cell growth of S. cerevisiae [].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. However, they are predicted to be integral membrane proteins (with several transmembrane segments).
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
