Members of this family are a variant form of the type II secretion system (T2SS) protein M, GspM, as found in several species of Pseudomonas. Members, including XcpZ, are short relatives to proteins in
, but are not recognised by that entry.
The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space [
]. T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK []. GspD has been shown to interact with the inner membrane component GspC []. The T2SS pseudopilus is a periplasmic filament composed of the major pseudopilin, EpsG, and four minor pseudopilins, EpsH, EpsI, EpsJ and EpsK. Pseudopilus is assembled by the polymerization of GspG (also known as PulG) subunits. Pseudopilin proteins have a conserved N-terminal hydrophobic segment followed by a more variable C-terminal periplasmic and globular domain [
].
Type II secretion system protein GspN, Leptospira-type
Type:
Family
Description:
Members of this family are the N (or GspN) protein of type II secretion systems (T2SS) [
] as found in Leptospira, Geobacter, Myxococcus, and several other genera. Sequence similarity to GspN in is extremely remote.
The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space [
]. T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK []. GspD has been shown to interact with the inner membrane component GspC []. The T2SS pseudopilus is a periplasmic filament composed of the major pseudopilin, EpsG, and four minor pseudopilins, EpsH, EpsI, EpsJ and EpsK. Pseudopilus is assembled by the polymerization of GspG (also known as PulG) subunits. Pseudopilin proteins have a conserved N-terminal hydrophobic segment followed by a more variable C-terminal periplasmic and globular domain [
].
LPS export ABC transporter, ATP-binding protein LptB
Type:
Family
Description:
Lipopolysaccharide (LPS) transport across the periplasmic space and its assembly at the Escherichia coli cell surface is carried out by a complex of seven Lpt proteins spanning the inner membrane (LptBCFG), the periplasm (LptA), and the outer membrane (LptDE). Members of this family are LptB, the ATP-binding cassette protein of the ABC transporter complex LptBFG involved in lipopolysaccharide export [
,
].
MoCo/4Fe-4S cofactor protein extended Tat translocation domain
Type:
Domain
Description:
This entry represents a forty-five residue domain in which the last six residues represent the start of a TAT (Twin-Arginine Translocation) sorting signal. TAT allows proteins already folded, with cofactor already bound, to transit the membrane and reach the periplasm with the ability to perform redox or other cofactor-dependent activities. TAT signals are not normally seen so far from a well-supported start site. Proteins containing this domain may all be mutually homologous, with both a molybdenum cofactor-binding domain and a 4Fe-4S dicluster-binding domain.
DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases [
]. DOCK proteins are required during several cellular processes, such as cell motility and phagocytosis. The N-terminal SH3 domain of the DOCK proteins functions as an inhibitor of GEF, which can be relieved upon its binding to the ELMO1-3 adaptor proteins, after their binding to active RhoG at the plasma membrane [,
]. DOCK family proteins are categorised into four subfamilies based on their sequence homology: DOCK-A subfamily (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11) []. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). DOCK4 is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. It activates small GTPases by exchanging bound GDP for free GTP. It plays a role in regulating dendritic growth and branching in hippocampal neurons, where it is highly expressed. It may also regulate spine morphology and synapse formation [
] and has been linked to autism, dyslexia, and schizophrenia [,
,
]. DOCK4 activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. DOCK4 plays a critical role in mediating TGF-beta's prometastatic effects in lung cancer [].This entry represents the DHR-2 domain of DOCK4, which contains the catalytic GEF activity for Rac and/or Cdc42.
von Willebrand factor C domain-containing protein 2-like
Type:
Family
Description:
This entry includes VWC2 (also known as Brorin) and VWC2L proteins. Brorin is a secreted BMP antagonist that promotes neurogenesis in mouse neural precursor cells [
]. VWC2L may also play roles in neural development and functions [].
This entry represents a group of plant proteins, including protein SHORT HYPOCOTYL IN WHITE LIGHT 1 (SHW1) from Arabidopsis. SHW1 is a serine-arginine-aspartate rich protein that regulates the abscisic acid (ABA) and light signaling pathways [
]. The shw1 mutants display shorter hypocotyl in the darkness. SHW1 acts as a negative regulator of photomorphogenesis []. SHW1 is a transmembrane protein with a nuclear localization signal.
Cdc13 is an essential yeast protein required for telomere length regulation and genome stability. Cdc13, like a number of single-stranded telomere binding proteins, consists of several oligonucleotide-oligosaccharide binding (OB) folds. These folds potentially arise from evolutionary gene duplication and are involved in multiple functions, including nucleic acid and protein binding and Cdc13 dimerization. This entry represents the OB2 domain, second OB-fold counting from the N terminus of Cdc13. Biochemical assays indicate OB2 is not involved in telomeric DNA or Stn1 binding. However, disruption of the OB2 dimer in full-length Cdc13 affects Cdc13-Stn1 association, leading to telomere length deregulation, increased temperature sensitivity, and Stn1 binding defects. Hence it is suggested that the dimerization of the OB2 domain of Cdc13 is required for proper Cdc13, Stn1, Ten1 (CST) assembly and productive telomere capping [
].
B-cell antigen receptor complex-associated protein alpha/beta chain
Type:
Family
Description:
The B-cell antigen receptor (BCR) consists of the membrane-bound immunoglobulin (mIg) comprising two heavy (H) and two light (L) chains and the signal-transducing Igalpha/Igbeta (CD79a/CD79b) heterodimer. This entry includes CD79a and CD79b. They contain an immunoreceptor tyrosine-based activation motif (ITAM) with two conserved tyrosines that are crucial for the development and maintenance of mature B cells [
]. Homologues are known from vertebrates.This family also includes Transmembrane and immunoglobulin domain-containing protein 2 (TMIGD2) which plays a role in cell-cell interaction, cell migration, and angiogenesis. It seems structurally related to CD79a/b based on structure prediction. Through interaction with HHLA2, costimulates T-cells in the context of TCR-mediated activation. It enhances T-cell proliferation and cytokine production via an AKT-dependent signaling cascade [
,
].
Doublecortin domain-containing protein 2, doublecortin-like domain 2
Type:
Domain
Description:
Doublecortin domain-containing protein 2 (DCDC2) interacts with the mediator of Wnt signalling dishevelled. The overexpression of DCDC2 inhibits beta-catenin-dependent Wnt signalling []. It also plays an important role in hair cell kinocilia and supporting cell primary cilia length regulation, likely via its role in microtubule formation and stabilisation []. It also affects length and signalling of primary cilia in neurons and has been associated with learning disabilities [,
]. Genetic variation in humans is associated with neonatal sclerosing cholangitis, a rare biliary disease leading to liver transplantation in childhood [].This entry represents the doublecortin-like domain 2 of DCDC2.
Type III secretion system effector protein YopE-like
Type:
Family
Description:
Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell
exterior. There have been four secretion systems described in animal enteropathogens, such as Salmonella and Yersinia, with further sequence similarities in plant pathogens like Ralstonia and Erwinia [
].The type III secretion system is of great interest, as it is used to transport virulence factors from the pathogen directly into the host cell
and is only triggered when the bacterium comes into close contact with the host. The protein subunits of the system are very similar to those of bacterial flagellar biosynthesis. However, while the latter forms a ring structure to allow secretion of flagellin and is an integral part of
the flagellum itself [], type III subunits in the outer membrane translocate secreted proteins through a channel-like structure.Exotoxins secreted by the type III system do not possess a secretion signal, and are considered unique for this reason [
]. Yersinia secrete a Rho GTPase-activating protein, YopE [,
], that disrupts the host cell actin cytoskeleton. YopE is regulated by another bacterial gene, SycE [], that enables the exotoxin to remain soluble in the bacterial cytoplasm. A similar protein, exoenzyme S from Pseudomonas aeruginosa, has both ADP-ribosylation and GTPase activity [,
]. This entry also includes ADP-ribosyltransferase toxin AexT from Aeromonas salmonicida that is directly involved in the toxicity for RTG-2 (rainbow trout gonad) fish cells [].This entry also includes Exoenzyme T (ExoT) from Pseudomonas aeruginosa. ExoT contains an N-terminal GTPase-activating protein (GAP) domain and a C-terminal ADP-ribosyltransferase (ADPRT) domain. Its ADPRT domain induces atypical anoikis by transforming an innocuous cellular protein, Crk, into a cytotoxin, which interferes with integrin survival signaling. Its GAP domain activity induces mitochondrial disruption in the target host cell by activating host caspases 3 and 9 that execute cellular death [
].
Bifunctional chloromethane dehalogenation methyltransferase corrinoid-binding protein CmuA
Type:
Family
Description:
The pathway of chloromethane utilization, which allows the microorganisms that possess it to grow with chloromethane as the sole carbon and energy source, is believed to be initiated by a corrinoid-dependent methyltransferase system involving methyltransferase I (CmuA) and methyltransferase II (CmuB), which transfer the methyl group of chloromethane onto tetrahydrofolate (H4folate) [
]. The methyl group of chloromethane is first transferred by the protein CmuA to a corrinoid protein, from where it is transferred to H4folate by CmuB, yielding methyl-H4folate [,
]. Both CmuA and CmuB display sequence similarity to methyltransferases of methanogenic archaea.CmuA is a two-domain methyltransferase/corrinoid-binding protein involved in methyl transfer from chloromethane to a corrin moiety. CmuA shows similarity to known methyltransferases as well as to their cognate corrinoid protein-binding proteins in the N-terminal and C-terminal parts of its sequence, respectively [
]. Mutation analysis shows that CmuA acts as methyltransferase I []. Mutation analysis shows that CmuA acts as methyltransferase I []. By analogy to similar methyltransferase systems, it is thought that CmuA acts as both the methyltransferase I and the corrinoid-binding protein in the dehalogenation of chloromethane []. Therefore, CmuA catalyses the first step of the chloromethane-degradation pathway, comprising the dehalogenation of chloromethane and the methylation of an associated cobalt corrin moiety.
Low affinity potassium transport system protein Kup
Type:
Family
Description:
This entry represents the low affinity potassium transport system Kup family of proteins. These proteins are involved in the uptake of K+ ions under hyper-osmotic stress at low pH [
]. Kup proteins are composed of two domains--an integral membrane domain that has 12 putative trans-membrane sections and a hydrophilic C-terminal domain.
CHD1 helical C-terminal domain containing protein 1-like
Type:
Family
Description:
This entry includes CHD1 helical C-terminal domain containing protein 1 (CHCT1, formerly known as C17orf64) and related proteins. CHCT1 may play a role in regulation of apoptosis [].
Thiolase-like protein type 1, additional C-terminal domain
Type:
Domain
Description:
This domain is found in thiolase-like protein type 1 (TLP1) present in Mycobacterium smegmatis. Thiolase enzymes are acetyl-coenzyme A acetyltransferases which convert two units of acetyl-CoA to acetoacetyl CoA in the mevalonate pathway. This domain is deemed an additional C-terminal region, much like the SPC2-thiolase present in mammals which has an additional C-terminal domain termed the sterol carrier protein-2 (SPC2). However, the additional C-terminal domain in TLP1 folds differently to the traditional SCP2-fold observed in mammalian SPC2-thiolase. The topology of the C-terminal domain of TLP1 is reminiscent of single strand nucleic acid binding proteins [
].
T6SS bacteria employ toxic effectors to inhibit rival cells and concurrently use effector cognate immunity proteins to protect their sibling cells. The effector and immunity pairs (E-I pairs) endow the bacteria with a great advantage in niche competition. This is the C-terminal domain of Tli4 (PA1509 in Pseudomonas aeruginosa). The Tle cognate immunity proteins (Tlis) can directly disable the transported Tle protein and thereby mediate the self-protection process. The Tle-Tli effector-immunity (E-I) pairs confer substantial advantage to the donor cell during interbacterial competition. Tli4 displays a two-domain conformation (domains I and II) and contains 17 β-strands and four helices. These two domains pack into a crab claw-like conformation functioning as an inhibitor of Tle4. Both domains adopt an alpha+beta architecture. Domain I features a central antiparallel β-sheet sandwiched by two helices and a short antiparallel β-sheet. This entry comprises the N-terminal domain I found in Tli4 proteins [
].
DNA mismatch repair protein HSM3, C-terminal domain
Type:
Domain
Description:
Hsm3 is a proteasome-dedicated chaperone that forms a base precursor, Hsm3-Rpt1-Rpt2-Rpn1 [
]. Hsm3 consists of 23 α-helices forming 11 repeats similar to HEAT repeats. This entry include the last 5 repeats at the C terminus.
Ribosome maturation protein Sdo1/SBDS, central domain superfamily
Type:
Homologous_superfamily
Description:
Proteins containing this domain are highly conserved in species ranging from archaea to vertebrates and plants [
], including several Shwachman-Bodian-Diamond syndrome (SBDS, OMIM 260400) proteins from both mouse and humans. Shwachman-Diamond syndrome is an autosomal recessive disorder with clinical features that include pancreatic exocrine insufficiency, haematological dysfunction and skeletal abnormalities. It is characterised by bone marrow failure and leukemia predisposition. Members of this superfamily play a role in RNA metabolism [,
]. In yeast Sdo1 is involved in the biogenesis of the 60S ribosomal subunit and translational activation of ribosomes. Together with the EF-2-like GTPase RIA1 (EfI1), it triggers the GTP-dependent release of TIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating TIF6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export. This data links defective late 60S subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition [].The SBDS protein is composed of three domains. The N-terminal (FYSH) domain is the most frequent target for disease mutations and contains a novel mixed alpha/β-fold, the central domain, represented in this entry, consists of a three-helical bundle and the C-terminal domain has a ferredoxin-like fold [
,
].
Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking [
,
]. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins, such as that from Schizosaccharomyces pombe, contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization []. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization []. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis [].This entry represents the second SH3 domain of Abp1 from fungi such as Schizosaccharomyces pombe.
Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking [
,
]. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins, such as that from Schizosaccharomyces pombe, contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization []. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization []. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis [].This entry represents the SH3 domain of fungal Abp1 and the first SH3 domain of app1 from Schizosacchormyces pombe.
SH3 domain-containing protein 19 (also known as Eve-1 or EBP) exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. Eve-1 interacts with ADAMs (A disintegrin and metalloprotease) and is required for ectodomain shedding of epidermal growth factor receptor ligands [
]. It inhibits Ras signaling [].This entry represents the first SH3 domain of Eve1.
SH3 domain-containing protein 19 (also known as Eve-1 or EBP) exists in multiple alternatively spliced isoforms. The longest isoform contains five SH3 domain in the C-terminal region and seven proline-rich motifs in the N-terminal region. Eve-1 interacts with ADAMs (A disintegrin and metalloprotease) and is required for ectodomain shedding of epidermal growth factor receptor ligands [
]. It inhibits Ras signaling [].This entry represents the third SH3 domain of Eve1.
DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases [
]. DOCK proteins are required during several cellular processes, such as cell motility and phagocytosis. The N-terminal SH3 domain of the DOCK proteins functions as an inhibitor of GEF, which can be relieved upon its binding to the ELMO1-3 adaptor proteins, after their binding to active RhoG at the plasma membrane [,
]. DOCK family proteins are categorised into four subfamilies based on their sequence homology: DOCK-A subfamily (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11) []. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). DOCK1, also called Dock180, and DOCK5 are class A DOCKs and are atypical guanine nucleotide exchange factors (GEFs) that lack the conventional Dbl homology (DH) domain. DOCK1 interacts with the scaffold protein Elmo and the resulting complex functions upstream of Rac in many biological events including phagocytosis of apoptotic cells, cell migration and invasion [
,
,
,
]. DOCK5 functions upstream of Rac1 to regulate osteoclast function []. Class A DOCKs also contain an SH3 domain at the N-terminal region and a PxxP motif at the C-terminal; they are specific GEFs for Rac. This entry represents the SH3 domain of DOCK1 and DOCK5. SH3 of DOCK1 binds to DHR-2 domain in an autoinhibitory manner; binding of Elmo to the SH3 domain of Dock1 exposes the DHR-2 domain and promotes GEF activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signalling pathway components, and mediating the formation of multiprotein complex assemblies.
Large cysteine-rich periplasmic protein OmcB-like, DUF11 domain
Type:
Domain
Description:
This group of sequences is represented by a conserved region of about 53 amino acids shared between regions, usually repeated, of proteins from a small number of phylogenetically distant prokaryotes. Examples include a 132-residue region found repeated in three of the five longest proteins of Bacillus anthracis, a 131-residue repeat in a cell wall-anchored protein of Enterococcus faecalis (Streptococcus faecalis), and a 120-residue repeat in Methanobacterium thermoautotrophicum. A similar region is found in some Chlamydia trachomatis outer membrane proteins. In C. trachomatis, three cysteine-rich proteins (also believed to be lipoproteins), MOMP, OMP6 and OMP3, make up the extracellular matrix of the outer membrane [
]. They are involved in the essential structural integrity of both the elementary body (EB) and recticulate body (RB) phase. They are thought to be involved in porin formation and, as these bacteria lack the peptidoglycan layer common to most Gram-negative microbes, such proteins are highly important in the pathogenicity of the organism.
In Methanothermobacter sp. CaT2, a DUF11-containing repeat hypothetical protein encoded by MTCT_1020 plays a key role as a membrane-bound adhesion protein in the aggregation of CaT2. DUF11-containing repeat domains are not involved in aggregation, but may be important for stabilizing the surface cell wall structures of CaT2 [
].
SLIT-ROBO Rho GTPase-activating protein 1, F-BAR domain
Type:
Domain
Description:
The SLIT-ROBO Rho GTPase-activating protein (srGAP) family consists of four members: srGAP1, -2, -3 and -4. They contain F-BAR, RhoGAP and SH3 domains. Their RhoGAP domain is involved in negative regulation of Rho GTPase activities important for cytoskeleton rearrangement [
]. The srGAP family members have an "inverse F-BAR"or IF-BAR domain that is distinct from other F-BAR domains such as FBP17. They are multifunctional adaptor proteins involved in various aspects of neuronal development [
].This entry represents the F-BAR domain of srGAP1. srGAP1, also called Rho GTPase-Activating Protein 13 (ARHGAP13), is a Cdc42- and RhoA-specific GAP and is expressed later in the development of CNS (central nervous system) tissues. It is an important downstream signaling molecule of Robo1 [
,
].
Centriolar and ciliogenesis-associated protein HYLS1, C-terminal domain
Type:
Domain
Description:
This entry represents the C-terminal domain of Centriolar and ciliogenesis-associated protein HYLS1. The HYLS1 gene shows alternative splicing and the transcript is found in multiple tissues during foetal development [
,
].
Baseplate structural protein Gp11, N-terminal domain superfamily
Type:
Homologous_superfamily
Description:
The bacteriophage baseplate controls host cell recognition, attachment, tail sheath contraction and viral DNA ejection. The baseplate is a multi-subunit assembly at the distal end of the tail, which is composed of long and short tail fibres [
]. The tail region is responsible for attachment to the host bacteria during infection: long tail fibres enable host receptor recognition, while irreversible attachment is via short tail fibres. Recognition and attachment induce a conformational transition of the baseplate from a hexagonal to a star-shaped structure. In viruses such as Bacteriophage T4, Gp11 acts as a structural protein to connect the short tail fibres to the baseplate, while Gp9 connects the baseplate with the long tail fibres. Both Gp9 and Gp11 are trimers. Each Gp11 monomer consists of three domains, which are entwined together in the trimer: the N-terminal domains of the three monomers form a central, trimeric, parallel coiled coil surrounded by the entwined middle finger domains; the C-terminal domains appear to be responsible for trimerisation [].This superfamily represents the N-terminal domain of Gp11, which has an α-helical structure that assumes an orthogonal bundle topology.
CD-NTase associated protein 4-like, DNA endonuclease domain
Type:
Domain
Description:
This entry corresponds to the N-terminal domain found in CD-NTase associated protein 4 (Cap4) from Enterobacter cloacae. This is the effector domain which has dsDNA nuclease activity, sharing structural homology with type II restriction endonucleases and it has the putative active-site conserved residues required for divalent metal coordination. It has a mixed β-sheet arrangement with α-helical bundles on the sides. This domain is inactive as a monomer; after Cap4 signal recognition through its C-terminal SAVED domain, it oligomerizes to closely locate two nuclease effector domains. This domain does not participate in ligand specificity and it has a promiscuous DNA cleavage response [
]. This domain can also be found in uncharacterised proteins from bacteria and archaea. CD-NTase-associated protein 4 (Cap4) is a member of a diverse family of bacterial receptors that specifically recognises nucleotide second messenger signals synthesised by cGAS/DncV-like nucleotidyltransferases (CD-NTases), that functions in CBASS immunity. It plays an essential role protecting bacteria from phage infections degrading dsDNA through its DNA endonuclease domain which is activated after ligand-induced oligomerization [
]. This domain is found in LmuA and AbpA proteins, which confer resistance to phage infections.
Transferrin-binding protein B, C-lobe/N-lobe beta barrel domain
Type:
Domain
Description:
Bacterial lipoproteins represent a large group of specialised membrane proteins that perform a variety of functions including maintenance and stabilization of the cell envelope, protein targeting and transit to the outer membrane, membrane biogenesis, and cell adherence [
]. Pathogenic Gram-negative bacteria within the Neisseriaceae and Pasteurellaceae families rely on a specialised uptake system, characterised by an essential surface receptor complex that acquires iron from host transferrin (Tf) and transports the iron across the outer membrane. They have an iron uptake system composed of surface exposed lipoprotein, Tf-binding protein B (TbpB), and an integral outer-membrane protein, Tf-binding protein A (TbpA), that together function to extract iron from the host iron binding glycoprotein (Tf).TbpB is a bilobed (N and C lobe) lipid-anchored protein with each lobe consisting of an eight-stranded β-barrel flanked by a 'handle' domain made up of four (N lobe) or eight (C lobe) β-strands [
]. TbpB extends from the outer membrane surface by virtue of an N-terminal peptide region that is anchored to the outer membrane by fatty acyl chains on the N-terminal cysteine and is involved in the initial capture of iron-loaded Tf []. This domain family is found in C and N lobe eight stranded β-barrel region of TbpB proteins. The eight-stranded barrel domains in N and C lobe draw comparisons to eight-stranded β-barrel outer-membrane protein W (OmpW). However, the barrel domains of TbpB have the hydrophobic residues line the inner surface of the β-barrels to create a stable hydrophobic core [].
Voltage-dependent calcium channel beta subunit-associated regulatory protein
Type:
Family
Description:
CBARP is a voltage-gated calcium channel (VGCC) beta-anchoring and -regulatory protein. It interacts via two cytosolic domains (I and II) with all Cavbeta subunit isoforms, affecting their subcellular localization and suppressing VGCC activity [
].
PHD finger protein 1 (PHF1) is a polycomb group (PcG) protein that plays a role in H3K27 methylation and Hox gene silencing [
]. The Tudor domain of human PHF1 recognises both H3K36me3 and H3tK27me3 [,
]. The interaction between PHF1 and H3K36me3 stabilises the nucleosome in a conformation in which the nucleosomal DNA is more accessible to DNA-binding regulatory proteins []. PHF1 is also involved in the response to DNA double-strand breaks [] and acts as a positive regulator of the p53 pathway [].This entry represents the second PHD finger of PHF1.
Flagellar motor switch protein FliN-like, C-terminal domain
Type:
Domain
Description:
This entry represents the C-terminal region of Flagellar motor switch proteins FliN and FliM and similar proteins mainly found in bacteria. This domain seems to play a key role in flagellation [
]. The flagellar motor switch in Escherichia coli and Salmonella typhimurium regulates the direction of
flagellar rotation and hence controls swimming behaviour. The switch is a complexapparatus that responds to signals transduced by the chemotaxis sensory signalling
system during chemotactic behaviour []. Theswitch complex comprises at least three proteins - FliG, FliM and FliN. It has been
shown that FliG interacts with FliM, FliM interacts with itself, and FliM interacts withFliN [
]. The proteinsare not particularly hydrophobic and may be peripheral to the membrane, possibly mounted
on the basal body M ring [,
].Proteins of the surface presentation of antigen (SpoA) group are involved in a secretory pathway responsible for the surface presentation of invasion plasmid antigen needed for the entry of Salmonella and other species into mammalian cells [
,
].They could play a role in preserving the translocation competence of the IPA antigens and are required for secretion of the three IPA proteins [].
This entry represents the C-terminal domain of GspG. GspG is the major pseudopilin of the type 2 secretion systems (T2SSs). The N-terminal hydrophobic helices of the GspG subunits arrange within the core of the pseudopilus, with the C-terminal domains and the Ca2+-binding sites located at the surface. The structure of GspG (also known as PulG) has been revealed [
]. The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space [
]. T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK []. GspD has been shown to interact with the inner membrane component GspC []. The T2SS pseudopilus is a periplasmic filament composed of the major pseudopilin, EpsG, and four minor pseudopilins, EpsH, EpsI, EpsJ and EpsK. Pseudopilus is assembled by the polymerization of GspG (also known as PulG) subunits. Pseudopilin proteins have a conserved N-terminal hydrophobic segment followed by a more variable C-terminal periplasmic and globular domain [
].
Mercuric transport protein periplasmic component/copper chaperone CopZ
Type:
Family
Description:
This entry includes a group of metal binding proteins, including copper chaperone CopZ [
] and mercuric transport protein periplasmic component MerP. They both contain a heavy-metal-associated (HMA) domain. CopZ is a chaperone that serves for the intracellular sequestration and transport of Cu+. It delivers Cu+ to the copper-exporting P-type ATPase A (CopA)[
].MerP is a mercury scavenger that specifically binds to one mercury ion and which passes it to the mercuric reductase (MerA) via the MerT protein. The structure of the mercuric ion-binding protein MerP from Shigella flexneri has been determined. The fold has been classed as a ferredoxin-like α-β sandwich, having a beta-alpha β-β α-β architecture, with the two α-helices overlaying a four-stranded anti-parallel β-sheet [
]. Structural differences between the reduced and mercury-bound forms of merP are localised to the metal-binding loop containing the consensus sequence GMTCXXC, the two cysteines of which are involved in bi-coordination of Hg2+[
].
RMP1, also called RNA-processing protein RMP1, or RNase MRP 23.6 kDa subunit, functions as part of ribonuclease MRP (RNase MRP), which is involved in rRNA processing in mitochondria. RNase MRP complex consists of an RNA moiety and at least 10 protein subunits including POP1, POP3, POP4, POP5, POP6, POP7, POP8, RMP1, RPP1 and SNM1, many of which are shared with the RNase P complex. RMP1 is required for proper rRNA processing. The entry represents a conserved region of RMP1, which is responsible for the RNA binding [,
,
].
Protein phosphatase 2A (PP2A) is a major intracellular protein
phosphatase that regulates multiple aspects of cell growth and metabolism.The ability of this widely distributed heterotrimeric enzyme to act on a
diverse array of substrates is largely controlled by the nature of itsregulatory B subunit. There are multiple families of B subunits, this family is called the B56 family [
].
Drought induced 19 protein type, zinc-binding domain
Type:
Domain
Description:
This zinc-binding domain is found in plant drought induced 19 (Di19) proteins, animal E3 ubiquitin-protein ligases (RNF114/KCMF1/RNF138/RNF125) and transcriptional repressors (ZEB1/ZEB2). Di19 has been found to be strongly expressed in both the roots and leaves of Arabidopsis thaliana during progressive drought [
]. KCMF1 and RNF114 are E3 ubiquitin-protein ligases [,
], while ZEB1 represses transcription by binding to the E box (5'-CANNTG-3') [].
Mg2+ transporter protein, CorA-like/Zinc transport protein ZntB
Type:
Family
Description:
This entry includes prokaryotic magnesium transport protein CorA and its related protein, zinc transport protein ZntB [
]. This entry also includes eukaryotic magnesium transporters, such as mitochondrial inner membrane magnesium transporter Mrs2 and magnesium transporter Alr1 and Alr2. These proteins are characterised by the conserved GMN motif at the end of the first of twoconserved transmembrane (TM) domains near the C terminus [
]. Thermotoga maritima CorA (TmCorA) has been reported to be an efflux system. It only has 2 TM domains,TM1 and TM2 [
,
,
]. The loop connecting TM1 and TM2 contains the conserved CorA signature motifs YGMNF and MPEL. With its N- and C-terminal ends face the cytosol and its similarity to the class II CorA (a CorA group lacking the MPEL motif and may transport divalent cations out of the cell), TmCorA is predicted to be primarily involved in ion efflux []. It forms a pentameric membrane protein channel featuring a possible ion discriminating aspartate ring at the cytoplasmic entrance of the pore and two distinct cytoplasmic metal binding sites per monomer, which could have regulatory roles [,
]. It has been suggested that eukaryotic CorA homologues have the same topology and overall structure as T. maritima CorA [
]. In budding yeasts, Mrs2 is an essential component of the major electrophoretic Mg2+ influx system in mitochondria []. Overexpression of Alr1 or Alr2 increases tolerance to Al3+ and Ga3+ ions []. Despite generally low sequence similarity, both human Mrs2 (also known as LPE10) and S. typhimurium CorA can restore Mg2+ uptake activity in Saccharomyces cerevisiae with inactive Mrs2 [].
Trafficking protein particle complex subunit 11, C-terminal
Type:
Domain
Description:
This entry represents a domain found in the C-terminal of TRAPPC11 (trafficking protein particle complex subunit 11) protein. TRAPPC11 is involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage [
].
Insulin gene enhancer protein ISL-1/2-like, LIM domain1
Type:
Domain
Description:
This entry represents the first LIM domain of ISL-1/2, which show two tandem N-terminal LIM domains and a C-terminal DNA binding homeodomain (
).
This group of proteins includes the DNA-binding transcriptional activators insulin gene enhancer proteins ISL-1/2 (also known as Islet-1/2) and its homologues from animals [,
]. ISL1 recognises and binds to the consensus octamer binding site 5'-ATAATTAA-3' in promoter of target genes [,
,
]. The early expression of ISL-1 in the developing hypothalamus determines the fate specification of melanocortinergic neurons and is essential for hypothalamic Pomc expression. It is required for melanocortin-induced satiety and normal adiposity throughout the entire lifespan []. ISL2 is a transcriptional factor that may define subclasses of motoneurons that segregate into columns in the spinal cord and select distinct axon pathways.
A-kinase anchor protein 10, PKA-binding (AKB) domain
Type:
Domain
Description:
A-kinase anchor proteins (AKAPs) coordinate the specificity of PKA signaling by facilitating the localization of the kinase to subcellular sites through their binding to regulatory (R) subunits of PKA. AKAP-10, also called PRKA10 or Dual-specific AKAP 2 (D-AKAP2), contains two regulator of G protein signaling (RGS)-like domains and a PKA-binding (AKB) domain [
]. This entry represents the AKB domain. The AKB domain of AKAP10 can bind to the dimerization/docking (D/D) domains of both RI and RII regulatory subunits of PKA. This domain also includes a C-terminal PDZ-binding motif that binds to PDZK1 and NHERF-1, allowing AKAP10 to link indirectly to membrane proteins [
]. Mutations inAKAP10 can alter its binding to R subunits, which may alter the targeting of PKA; some AKAP10 mutations are associated with abnormalities including hypertension, increased risk of severe arrhythmias during kidney transplantation, and familial breast cancer [
,
,
].
Ankyrin repeat and SAM domain-containing protein 3
Type:
Family
Description:
This group of proteins includes Ankyrin repeat and SAM domain-containing protein 3 (ANKS3), which may be involved in vasopressin signalling in the kidney [
].
PHD and RING finger domain-containing protein 1-like
Type:
Family
Description:
This entry represents a group of eukaryotic proteins, including PHD and RING finger domain-containing protein 1 from human and its orthologue from S. pombe. The function of these proteins is unknown.
Oryzines biosynthesis cluster protein J/Cupin-domain-containing oxidoreductase virC-like
Type:
Family
Description:
This family includes bacterial and fungal sequences which contain a cupin domain. This family includes oryzines biosynthesis cluster protein J (OryJ) which is part of the gene cluster that mediates the biosynthesis of oryzines, natural products with an unusual maleidride backbone [
], VirC, which is part of the gene cluster that mediates the biosynthesis of virensols and trichoxide, fungal natural products that contain or are derived from a salicylaldehyde core [].
Predicted [NiFe]-hydrogenase-3-type complex Eha, membrane protein EhaF
Type:
Family
Description:
[NiFe] hydrogenases function in H2 metabolism in a variety of microorganisms, enabling them to use H2 as a source of reducing equivalent under aerobic and anaerobic conditions [NiFe]hydrogenases consist of two subunits, hydrogenase large and hydrogenase small. The large subunit contains the binuclear [NiFe] active site, while the small subunit binds at least one [4Fe-4S]cluster [
].Energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type) form a distinct group within the [NiFe] hydrogenase family [,
,
]. Members of this subgroup include:Hydrogenase 3 and 4 (Hyc and Hyf) from Escherichia coliCO-induced hydrogenase (Coo) from Rhodospirillum rubrumMbh hydrogenase from Pyrococcus furiosusEha and Ehb hydrogenases from Methanothermobacter speciesEch hydrogenase from Methanosarcina barkeriEnergy-converting [NiFe] hydrogenases are membrane-bound enzymes with a six-subunit core: the large and small hydrogenase subunits, plus two hydrophilic proteins and two integral membrane proteins. Their large and small subunits show little sequence similarity to other [NiFe]hydrogenases, except for key conserved residues coordinating the active site and [FeS] cluster. However, they show considerable sequence similarity to the six-subunit, energy-conserving NADH:quinone oxidoreductases (complex I), which are present in cytoplasmic membranes of many bacteria and in inner mitochondrial membranes. However, the reactions they catalyse differ significantly from complex I. Energy-converting [NiFe]hydrogenases function as ion pumps.Eha and Ehb hydrogenases contain extra subunits in addition to those shared by other energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type). Eha contains a 6[4Fe-4S] polyferredoxin, a 10[4F-4S]polyferredoxin, ten other predicted integral membrane proteins (EhaA
, EhaB
, EhaC
, EhaD
, EhaE
, EhaF
, EhaG
, EhaI
, EhaK
, EhaL
and
) and four hydrophilic subunits (EhaM, EhaR, EhS, EhT) [
,
]. The ten predicted integral membrane proteins are absent from Ech, Coo, Hyc and Hyf complexes, which may have simpler membrane components than Eha. Eha and Ehb catalyse the reduction of low-potential redox carriers (e.g. ferredoxins or polyferredoxins), which then might function as electron donors to oxidoreductases.Based on sequence similarity and genome context analysis, other organisms such as Methanopyrus kandleri, Methanocaldococcus jannaschii, and Methanothermobacter marburgensis also encode Eha-like [NiFe]-hydrogenase-3-type complexes and have very similar ehaoperon structure.
This entry represents small membrane proteins that are predicted to be the EhaF transmembrane subunits of multi-subunit membrane-bound [NiFe]-hydrogenase Eha complexes.
Predicted [NiFe]-hydrogenase-3-type complex Eha, membrane protein EhaB
Type:
Family
Description:
[NiFe] hydrogenases function in H2 metabolism in a variety of microorganisms, enabling them to use H2 as a source of reducing equivalent under aerobic and anaerobic conditions [NiFe]hydrogenases consist of two subunits, hydrogenase large and hydrogenase small. The large subunit contains the binuclear [NiFe] active site, while the small subunit binds at least one [4Fe-4S]cluster [
].Energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type) form a distinct group within the [NiFe] hydrogenase family [,
,
]. Members of this subgroup include:Hydrogenase 3 and 4 (Hyc and Hyf) from Escherichia coliCO-induced hydrogenase (Coo) from Rhodospirillum rubrumMbh hydrogenase from Pyrococcus furiosusEha and Ehb hydrogenases from Methanothermobacter speciesEch hydrogenase from Methanosarcina barkeriEnergy-converting [NiFe] hydrogenases are membrane-bound enzymes with a six-subunit core: the large and small hydrogenase subunits, plus two hydrophilic proteins and two integral membrane proteins. Their large and small subunits show little sequence similarity to other [NiFe]hydrogenases, except for key conserved residues coordinating the active site and [FeS] cluster. However, they show considerable sequence similarity to the six-subunit, energy-conserving NADH:quinone oxidoreductases (complex I), which are present in cytoplasmic membranes of many bacteria and in inner mitochondrial membranes. However, the reactions they catalyse differ significantly from complex I. Energy-converting [NiFe]hydrogenases function as ion pumps.Eha and Ehb hydrogenases contain extra subunits in addition to those shared by other energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type). Eha contains a 6[4Fe-4S] polyferredoxin, a 10[4F-4S]polyferredoxin, ten other predicted integral membrane proteins (EhaA
, EhaB
, EhaC
, EhaD
, EhaE
, EhaF
, EhaG
, EhaI
, EhaK
, EhaL
and
) and four hydrophilic subunits (EhaM, EhaR, EhS, EhT) [
,
]. The ten predicted integral membrane proteins are absent from Ech, Coo, Hyc and Hyf complexes, which may have simpler membrane components than Eha. Eha and Ehb catalyse the reduction of low-potential redox carriers (e.g. ferredoxins or polyferredoxins), which then might function as electron donors to oxidoreductases.Based on sequence similarity and genome context analysis, other organisms such as Methanopyrus kandleri, Methanocaldococcus jannaschii, and Methanothermobacter marburgensis also encode Eha-like [NiFe]-hydrogenase-3-type complexes and have very similar
ehaoperon structure.
This entry represents small membrane proteins that are predicted to be the EhaB transmembrane subunits of multi-subunit membrane-bound [NiFe]-hydrogenase Eha complexes.
Predicted [NiFe]-hydrogenase-3-type complex Eha, membrane protein EhaK
Type:
Family
Description:
[NiFe] hydrogenases function in H2 metabolism in a variety of microorganisms, enabling them to use H2 as a source of reducing equivalent under aerobic and anaerobic conditions [NiFe]hydrogenases consist of two subunits, hydrogenase large and hydrogenase small. The large subunit contains the binuclear [NiFe] active site, while the small subunit binds at least one [4Fe-4S]cluster [
].Energy-converting [NiFe]hydrogenases (or [NiFe]-hydrogenase-3-type) form a distinct group within the [NiFe]hydrogenase family [
,
,
]. Members of this subgroup include:Hydrogenase 3 and 4 (Hyc and Hyf) from Escherichia coliCO-induced hydrogenase (Coo) from Rhodospirillum rubrumMbh hydrogenase from Pyrococcus furiosusEha and Ehb hydrogenases from Methanothermobacter speciesEch hydrogenase from Methanosarcina barkeriEnergy-converting [NiFe] hydrogenases are membrane-bound enzymes with a six-subunit core: the large and small hydrogenase subunits, plus two hydrophilic proteins and two integral membrane proteins. Their large and small subunits show little sequence similarity to other [NiFe]hydrogenases, except for key conserved residues coordinating the active site and [FeS] cluster. However, they show considerable sequence similarity to the six-subunit, energy-conserving NADH:quinone oxidoreductases (complex I), which are present in cytoplasmic membranes of many bacteria and in inner mitochondrial membranes. However, the reactions they catalyse differ significantly from complex I. Energy-converting [NiFe]hydrogenases function as ion pumps.Eha and Ehb hydrogenases contain extra subunits in addition to those shared by other energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type). Eha contains a 6[4Fe-4S] polyferredoxin, a 10[4F-4S]polyferredoxin, ten other predicted integral membrane proteins (EhaA
, EhaB
, EhaC
, EhaD
, EhaE
, EhaF
, EhaG
, EhaI
, EhaK
, EhaL
and
) and four hydrophilic subunits (EhaM, EhaR, EhS, EhT) [
,
]. The ten predicted integral membrane proteins are absent from Ech, Coo, Hyc and Hyf complexes, which may have simpler membrane components than Eha. Eha and Ehb catalyse the reduction of low-potential redox carriers (e.g. ferredoxins or polyferredoxins), which then might function as electron donors to oxidoreductases.Based on sequence similarity and genome context analysis, other organisms such as Methanopyrus kandleri, Methanocaldococcus jannaschii, and Methanothermobacter marburgensis also encode Eha-like [NiFe]-hydrogenase-3-type complexes and have very similar ehaoperon structure.
This entry represents small membrane proteins that are predicted to be the EhaK transmembrane subunits of multi-subunit membrane-bound [NiFe]-hydrogenase Eha complexes.
Predicted [NiFe]-hydrogenase-3-type complex Eha, membrane protein EhaE
Type:
Family
Description:
[NiFe] hydrogenases function in H2 metabolism in a variety of microorganisms, enabling them to use H2 as a source of reducing equivalent under aerobic and anaerobic conditions [NiFe]hydrogenases consist of two subunits, hydrogenase large and hydrogenase small. The large subunit contains the binuclear [NiFe] active site, while the small subunit binds at least one [4Fe-4S]cluster [
].Energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type) form a distinct group within the [NiFe] hydrogenase family [,
,
]. Members of this subgroup include:Hydrogenase 3 and 4 (Hyc and Hyf) from Escherichia coliCO-induced hydrogenase (Coo) from Rhodospirillum rubrumMbh hydrogenase from Pyrococcus furiosusEha and Ehb hydrogenases from Methanothermobacter speciesEch hydrogenase from Methanosarcina barkeriEnergy-converting [NiFe] hydrogenases are membrane-bound enzymes with a six-subunit core: the large and small hydrogenase subunits, plus two hydrophilic proteins and two integral membrane proteins. Their large and small subunits show little sequence similarity to other [NiFe]hydrogenases, except for key conserved residues coordinating the active site and [FeS] cluster. However, they show considerable sequence similarity to the six-subunit, energy-conserving NADH:quinone oxidoreductases (complex I), which are present in cytoplasmic membranes of many bacteria and in inner mitochondrial membranes. However, the reactions they catalyse differ significantly from complex I. Energy-converting [NiFe]hydrogenases function as ion pumps.Eha and Ehb hydrogenases contain extra subunits in addition to those shared by other energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type). Eha contains a 6[4Fe-4S] polyferredoxin, a 10[4F-4S]polyferredoxin, ten other predicted integral membrane proteins (EhaA
, EhaB
, EhaC
, EhaD
, EhaE
, EhaF
, EhaG
, EhaI
, EhaK
, EhaL
and
) and four hydrophilic subunits (EhaM, EhaR, EhS, EhT) [
,
]. The ten predicted integral membrane proteins are absent from Ech, Coo, Hyc and Hyf complexes, which may have simpler membrane components than Eha. Eha and Ehb catalyse the reduction of low-potential redox carriers (e.g. ferredoxins or polyferredoxins), which then might function as electron donors to oxidoreductases.Based on sequence similarity and genome context analysis, other organisms such as Methanopyrus kandleri, Methanocaldococcus jannaschii, and Methanothermobacter marburgensis also encode Eha-like [NiFe]-hydrogenase-3-type complexes and have very similar ehaoperon structure.
This entry represents small membrane proteins that are predicted to be the EhaE transmembrane subunits of multi-subunit membrane-bound [NiFe]-hydrogenase Eha complexes.
Predicted [NiFe]-hydrogenase-3-type complex Eha, membrane protein EhaI
Type:
Family
Description:
[NiFe] hydrogenases function in H2 metabolism in a variety of microorganisms, enabling them to use H2 as a source of reducing equivalent under aerobic and anaerobic conditions [NiFe]hydrogenases consist of two subunits, hydrogenase large and hydrogenase small. The large subunit contains the binuclear [NiFe] active site, while the small subunit binds at least one [4Fe-4S]cluster [
].Energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type) form a distinct group within the [NiFe] hydrogenase family [,
,
]. Members of this subgroup include:Hydrogenase 3 and 4 (Hyc and Hyf) from Escherichia coliCO-induced hydrogenase (Coo) from Rhodospirillum rubrumMbh hydrogenase from Pyrococcus furiosusEha and Ehb hydrogenases from Methanothermobacter speciesEch hydrogenase from Methanosarcina barkeriEnergy-converting [NiFe] hydrogenases are membrane-bound enzymes with a six-subunit core: the large and small hydrogenase subunits, plus two hydrophilic proteins and two integral membrane proteins. Their large and small subunits show little sequence similarity to other [NiFe]hydrogenases, except for key conserved residues coordinating the active site and [FeS] cluster. However, they show considerable sequence similarity to the six-subunit, energy-conserving NADH:quinone oxidoreductases (complex I), which are present in cytoplasmic membranes of many bacteria and in inner mitochondrial membranes. However, the reactions they catalyse differ significantly from complex I. Energy-converting [NiFe]hydrogenases function as ion pumps.Eha and Ehb hydrogenases contain extra subunits in addition to those shared by other energy-converting [NiFe] hydrogenases (or [NiFe]-hydrogenase-3-type). Eha contains a 6[4Fe-4S] polyferredoxin, a 10[4F-4S]polyferredoxin, ten other predicted integral membrane proteins (EhaA
, EhaB
, EhaC
, EhaD
, EhaE
, EhaF
, EhaG
, EhaI
, EhaK
, EhaL
and
) and four hydrophilic subunits (EhaM, EhaR, EhS, EhT) [
,
]. The ten predicted integral membrane proteins are absent from Ech, Coo, Hyc and Hyf complexes, which may have simpler membrane components than Eha. Eha and Ehb catalyse the reduction of low-potential redox carriers (e.g. ferredoxins or polyferredoxins), which then might function as electron donors to oxidoreductases.Based on sequence similarity and genome context analysis, other organisms such as Methanopyrus kandleri, Methanocaldococcus jannaschii, and Methanothermobacter marburgensis also encode Eha-like [NiFe]-hydrogenase-3-type complexes and have very similar ehaoperon structure.
This entry represents small membrane proteins that are predicted to be the EhaI transmembrane subunits of multi-subunit membrane-bound [NiFe]-hydrogenase Eha complexes.
Protein of unknown function DUF3048, C-terminal domain
Type:
Domain
Description:
This entry represents the C-terminal domain of a group of proteins with unknown function. Proteins containing this domain include the YerB protein from Bacillus subtilis. YerB interacts with PcrA helicase. The interaction is not essential for cell viability or repair of UV-induced lesions [
].
Small zinc finger protein HVO_2753-like, zinc-binding pocket
Type:
Domain
Description:
This domain is present in a group of archaeal proteins, including HVO_2753 (also known as Small CPxCG-related zinc finger protein) from Haloferax volcanii [
]. NMR 3D structure analysis revealed the content of four C(P)XCG motifs, suggesting the presence of two zinc-binding pockets (ZBPs). However, only C(P)XCG motifs 2 and 4 (comprising Cys-32 to Cys-35 and Cys-50 to Cys-53) form a ZBP and binds one zinc atom, while C(P)XCG motifs 1 and 3 (comprising Cys-12 to Cys-15 and Cys-39 to Cys-42) form a four-Cys cluster that do not bind zinc. The four C(P)XCG motifs are critical for protein stability, folding and functionality [].
Human herpes virus-8, Protein K1, cytoplasmic domain
Type:
Domain
Description:
This entry represents a domain thought to to be at the cytoplasmic region of the Protein K1 from Human herpesvirus 8. This protein promotes host cell survival pathways and may contribute to pathogenesis by preventing infected cells from undergoing apoptosis. It is a highly glycosylated cytoplasmic and membrane protein similar to the immunoglobulin receptor family that is expressed as an inducible early-lytic-cycle gene product in primary effusion lymphoma cell-lines [
,
,
,
,
].
Dispersed gene family protein 1 of Trypanosoma cruzi is likely to be highly expressed, and is expressed from the sub-telomeric region [
]. However, its function is not known. This entry represents domain 4 on this protein.
Herpes simplex virus, Tegument protein VP16, C-terminal
Type:
Domain
Description:
This domain is found in the C-terminal region of the HSV virion protein 16 (VP16 or Alpha-TIF) from Herpes Simplex virus. It appears in association with
and is about 30 amino acids in length. It is the carboxyl subdomain of the acidic transcriptional activation domain.
VP16 is a transcription promoter, an essential activator of viral immediate early (IE) promoters (alpha genes) during the lytic phase of viral infection. The protein associates with cellular transcription factors and DNA binding proteins to to enhance transcription rates. Such proteins include TATA binding protein, CBP, TBP-binding protein, etc. The C-terminal residues of the protein are responsible for transcriptional activation. Within the C-terminal region there are two activation regions that can independently and cooperatively activate transcription [
,
,
].
Nepovirus subgroup A, RNA2 polyprotein, Protein 2A
Type:
Domain
Description:
Nepoviruses are plant viruses that, together with comoviruses and picornaviruses, are classified in the picornavirus superfamily of plus strand single-stranded RNA viruses. Its genome consist of two single-stranded RNAs, both required for infection [
]. RNA2 from the subgroup A of these viruses encode the polyprotein P2, which includes Protein 2A, the cell-to-cell movement protein and the coat protein [
]. This entry includes the N-terminal region of the RNA2 polyprotein, termed Protein 2A, which is implicated in the replication RNA2 [
,
]. This domain is normally found in association with ,
and
.
Nuclear abundant poly(A) RNA-binding protein Nab2, N-terminal
Type:
Domain
Description:
Nab2 is a yeast heterogeneous nuclear ribonucleoprotein that modulates poly(A) tail length and mRNA. This is the N-terminal domain of the protein which mediates interactions with the C-terminal globular domain, Myosin-like protein 1 and the mRNA export factor, Gfd1 [
]. The N-terminal domain of Nab2 shows a structure of a helical fold. The N-terminal domain of Nab2 isthought to mediate protein:protein interactions that facilitate the nuclear export of mRNA [
]. An essential hydrophobic Phe73 patch on the N-terminal domain is thought to be an important component of the interface between Nab2 and Mlp1 [].
LysM and putative peptidoglycan-binding domain-containing protein 1-4
Type:
Family
Description:
This entry represents a group of LysM and putative peptidoglycan-binding domain-containing proteins, including LYSMD1-4 from humans. The lysin motif (LysM) of LysMDs is likely related to a previously described peptidoglycan-binding LysM found in bacteria. LysMD3 is a type II membrane protein [
].
CBY1-interacting BAR domain-containing protein 1/2, BAR domain
Type:
Domain
Description:
BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions [
]. This group is composed of CBY1-interacting BAR domain-containing protein 1/2 (also known as the family with sequence similarity 92 (FAM92)), which were originally identified by the presence of the unknown domain DUF1208. This domain shows similarity to the BAR domains of sorting nexins. Mammals contain at least two member types, CBAR1 (FAM92A) and CBAR2 (FAM92B), which may exist in many variants. These may be involved in ciliogenesis regulation during limb morphogenesis [,
]. Human CBAR1 plays an important role in the mitochondrial function and is essential for maintaining mitochondrial morphology and inner membrane ultrastructure []. The Xenopus homologue of CBAR1A (FAM92A1), xVAP019, is essential for embryo survival and cell differentiation. CBAR1A may be involved in regulating cell proliferation and apoptosis [,
,
].
Conserved hypothetical protein CHP04066, peptide maturation system
Type:
Family
Description:
Members of this protein family occur in various Clostridial genomes, always in the context of a short peptide, which is likely to be a bacteriocin, and a radical SAM protein that is predicted to modify the short peptide. Sequence analysis suggests a relationship between family members and archaeal proteins designated as subunits of an H+-transporting two-sector ATPase. Family members are candidates to act in either maturation or immunity.
Quinohemoprotein amine dehydrogenase, gamma subunit maturation protein
Type:
Family
Description:
Members of this protein family are radical SAM enzymes responsible for post-translational modifications to the gamma subunit of quinohemoprotein amine dehydrogenases. It has been suggested that this protein is responsible for intrapeptidyl thioether cross-linking rather than cysteine tryptophylquinone biogenesis in the gamma subunit [
].
Dispersed gene family protein 1 of Trypanosoma cruzi is likely to be highly expressed, and is expressed from the sub-telomeric region [
]. However, its function is not known. This entry represents domain 5 on this protein, found downstream the C-terminal domain.
Recombination, repair and ssDNA binding protein UvsY
Type:
Family
Description:
UvsY protein enhances the rate of single-stranded-DNA-dependent ATP hydrolysis by UvsX protein. The enhancement of ATP hydrolysis by UvsY protein is shown to result from the ability of UvsY protein to increase the affinity of UvsX protein for single-stranded DNA [
].
Lipoprotein-releasing system transmembrane protein LolE, gammaproteobacteria type
Type:
Family
Description:
This protein is part of an unusual ABC transporter complex that releases lipoproteins from the periplasmic side of the bacterial inner membrane, rather than transport any substrate across the inner membrane. In some species, the permease-like transmembrane protein is represented by two paralogs, LolC and LolE, both in the LolCDE complex [
].
Mitogen-activated protein (MAP) kinase kinase kinase kinase
Type:
Family
Description:
Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process.
Protein kinases fall into three broad classes, characterised with respect to substrate specificity []:Serine/threonine-protein kinasesTyrosine-protein kinasesDual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)Protein kinase function is evolutionarily conserved from Escherichia coli to human [
]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation []. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [].Eukaryotic serine-threonine mitogen-activated protein (MAP) kinases are key regulators of cellular signal transduction systems and are conserved from Saccharomyces cerevisiae (Baker's yeast) to human beings. MAPK pathways are signalling cascades differentially regulated by growth factors, mitogens, hormones and stress which mediate cell growth, differentiation and survival. MAPK activity is regulated through a (usually) three-tiered cascade composed of a MAPK, a MAPK kinase (MAPKK, MEK) and a MAPK kinase kinase (MAPKK, MEKK). Substrates for the MAPKs include other kinases and transcription factors [
]. Mammals express at least four distinctly related groups of MAPKs, extracellularly-regulated kinases (ERKs), c-jun N-terminal kinases (JNKs), p38 proteins and ERK5. Plant MAPK pathways have attracted increasing interest, resulting in the isolation of a large number of different components of MAPK cascades. MAPKs play important roles in the signalling of most plant hormones and in developmental processes [
]. In the budding yeast S. cerevisiae, four separate but structurally related mitogen-activated protein kinase (MAPK)activation pathways are known, regulating mating, cell integrity and osmosity [].Enzymes in this family are characterised by two domains separated by a deep channel where potential substrates might bind. The N-terminal domain creates a binding pocket for the adenine ring of ATP, and the C-terminal domain contains the catalytic base, magnesium binding sites and phosphorylation lip [
]. Almost all MAPKs possess a conserved TXY motif in which both the threonine andtyrosine residues are phosphorylated during activation of the enzyme by
upstream dual-specificity MAP kinase kinases (MAPKKs).This group represents a mitogen-activated protein kinase kinase kinase kinase, which may play a role in the response to environmental stress. It appears to act upstream of the JUN N-terminal pathway [
].
Cytadherence high molecular weight protein 1 N-terminal
Type:
Domain
Description:
This entry describes the N-terminal region of the Mycoplasma cytadherence protein high molecular weight protein 1 (HMW1), up to but not including the first EAGR box domain. The apparent orthologs in different Mycoplasma species differ profoundly in archictecture C-terminally to the region described by this entry. HMW1 is a component of the cytoskeleton-like structure which stabilises the shape of the wall-less Mycoplasma. This cytoskeleton-like network of accessory proteins containing HMW proteins 1 to 5 allows the proper anchoring of cytadhesin proteins in the mycoplasmal membrane at the attachment organelle [
].
Protein of unknown function DUF762, Coxiella burnetii
Type:
Family
Description:
This family consists several of several uncharacterised proteins from the bacterium Coxiella burnetii. C. burnetii is the causative agent of the Q fever disease.
Zinc finger domain-containing protein 24, zinc-binding domain
Type:
Domain
Description:
Zcchc24 encodes a protein containing two zinc finger domains from the zf-CCHC and zf-3CxxC superfamilies [
]. This entry represents the zf-3CxxC domain.
GTPase-associated protein 1, N-terminal domain type 2
Type:
Domain
Description:
GTPase-associated protein 1 (GAP1) is part of the GTPase-centric systems, a class of NTP-dependent biological conflict systems. It is comprised of three clearly distinguishable globular domains: GAP1-N, GAP1-M and GAP1-C. GAP1 occurs in two distinct subtypes that are readily distinguished by versions of the GAP1-N domain: GAP1-N1 and GAP1-N2 [
].This entry represents the N2 domain (GAP1-N2) found in GAP1. This domain is predicted to mediate effector-GAP1 interactions.
TonB-dependent outer membrane protein SusC/RagA, conserved site
Type:
Conserved_site
Description:
This entry describes a short conserved site found in the SusC/RagA family of outer membrane proteins from the Bacteriodetes. While many TonB-dependent outer membrane receptors are associated with siderophore import, this family seems to include generalized nutrient receptors that may convey fairly large oligomers of protein or carbohydrate. The family occurs in high copy numbers in the most abundant species of the human gut microbiome.
Ribosomal peptide maturation radical SAM protein 1
Type:
Family
Description:
TOMM (
) and Nif11-like leader peptide (
) describe bacteriocin precursor families to occur often in large paralogous families and are subject to various modifications, including by LanM family lantibiotic synthases and by cyclodehydratases. This entry represents a radical SAM protein family that regularly occurs in the context of these bacteriocins, and may occur where other familiar peptide modification enzymes are absent [
,
].
The sequence of this family is highly conserved and carries a nuclear export signal from residues 31-55, and RNA binding/nuclear localisation signals of RRDR at residue 76 and KRRRK at residue 159. Rev is an essential regulatory protein required for nucleocytoplasmic transport of incompletely spliced viral mRNAs that encode structural proteins. Rev has been shown to down-regulate the expression of viral late genes and alter sensitivity to Gag-specific cytotoxic-T-lymphocytes (CTL). Equine infectious anaemia virus (EIAV) exhibits a high rate of genetic variation in vivo, and results in a clinically variable disease in infected horses.
Retroviral nucleocapsid Gag protein p24, C-terminal domain
Type:
Domain
Description:
The Gag protein from retroviruses, also known as p24, forms the inner protein layer of the nucleocapsid. It is composed of two domains, the N-terminal domain (NTD), which contributes to viral core formation, and the C-terminal domain (CTD), which is required for capsid dimerisation, Gag oligomerization and viral formation [,
]. This protein performs highly complex orchestrated tasks during the assembly, budding, maturation and infection stages of the viral replication cycle. During viral assembly, the proteins form membrane associations and self-associations that ultimately result in budding of an immature virion from the infected cell. Gag precursors also function during viral assembly to selectively bind and package two plus strands of genomic RNA. ELISA tests for p24 is the most commonly used method to demonstrate virus replication both in vivoand
in vitro[
,
].This is the C-terminal domain of retroviral p24 nucleocapsid protein, which contains a highly conserved region across retroviruses, the major homology region (MHR). The MHR is essential for the stability and folding of the monomer and hence for viral assembly, maturation and infectivity. This is a globular domain, composed of four helices and an extended N-terminal strand that forms a dimer through parallel packing of helix 2. The MHR dimer is a target for the development of anti-HIV drugs [,
,
].
Bridge-like lipid transfer protein family member 1
Type:
Family
Description:
Bridge-like lipid transfer protein family member 1 (BLTP1, formerly known as Tweek/KIAA1109 in human) is a tube-forming lipid transport protein which provides phosphatidylethanolamine for glycosylphosphatidylinositol (GPI) anchor synthesis in the endoplasmic reticulum. It plays a role in endosomal trafficking and endosome recycling and it is also involved in the actin cytoskeleton and cilia structural dynamics [
,
]. BLTP1 also acts as a regulator of phagocytosis []. In humans, it has been associated with rheumatoid arthritis [,
]. Mutations of the BLTP1 gene has been associated with Alkuraya-Kucinskas syndrome (MIM 617822), a severe disorder of brain development and arthrogryposis [].Members of this entry belong to the repeating β-groove (RBG) superfamily together with VPS13, ATG2, SHIP164, BLTP2/FMP27, which are all conserved lipid transfer proteins containing long hydrophobic grooves [
]. They all share the same structure comprising multiple repeating modules consisting of five β-sheets followed by a loop.
DNA packaging protein FI, C-terminal beta-strand domain
Type:
Homologous_superfamily
Description:
DNA packaging protein FI is a two-domain protein required for efficient DNA packaging and in lambda bacteriophage head assembly. This entry represents the C-terminal domain responsible for the head binding activity [
]. It adopts a β-strand fold, presents several unstructured regions and a conserved EEE sequence motif.
ORF16 (or gp16) is a tail-phage P2-like protein that forms part of the base-plate at the tip of the phage tail. The whole base-plate complex is involved in host recognition and attachment, and consists of several proteins derived from consecutive open-reading-frames. This central domain is expressed from ORF16 in the lactococcal P2-phage and forms a trimer. ORF16 is a four domain protein that adopts a fold comparable to that of gp27 of myophage T4 [
].This superfamily represents the domains 1 and 2 of the ORF16 protein [
].
Stimulated by Retinoic Acid Gene 8 (Stra8) is required for the transition into meiosis in both female and male germ cells. In mammals, Stra8 is expressed in embryonic ovaries just before meiotic initiation, whereas its expression in testes is first detected after birth [
]. Retinoic acid signalling is required for the expression of Stra8 and thereby meiotic initiation in embryonic ovaries [,
].
Stimulator of interferon genes protein homolog, C-terminal
Type:
Domain
Description:
This entry represents the C-terminal domain of STING homologues from arthropods.STING (stimulator of interferon genes, also known as MITA, ERIS, MPYS and TMEM173) is a master regulator that mediates cytokine production in response to microbial invasion by directly sensing bacterial secondary messengers such as the cyclic dinucleotide bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) and leading to the activation of IFN regulatory factor 3 (IRF3) through TANK-binding kinase 1 (TBK1) stimulation [
,
]. STING is also a signaling adaptor in the IFN response to cytosolic DNA. This detection of foreign materials is the first step to a successful immune responses. STING is localized in the ER and comprised of an predicted N-terminal transmembrane region and a C-terminal c-di-GMP binding domain [,
,
,
,
].
Mesoderm induction early response protein 1/3, C-terminal
Type:
Domain
Description:
This domain is found at the C terminus of Mesoderm induction early response proteins 1 and 3 (MIER1/3). MIER1 is a transcriptional repressor that regulates the expression of a number of genes including SP1 target genes, recruiting histone deacetylase 1 (HDAC1) through its ELM2 domain. It has two isoforms, alpha and beta, which differ in their C-terminal domains, both of them being able to interact with HDAC1. The gene encoding MIER3 has been identified as a candidate cancer susceptibility gene [
]. MIER1 and 3 share two regions of high homology, one at the N terminus and the second at the C terminus, represented in this entry, which consists of a short region located immediately downstream of the SANT extension that is 84% identical [,
].
50S ribosomal protein L10, insertion domain superfamily
Type:
Homologous_superfamily
Description:
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].This superfamily comprises the insertion domain of the ribosomal protein L10 found in the large subunit (50S) of the ribosome. The entry contains homologues such as archaebacterial acidic ribosomal protein P0 homologue (L10E) and the eukaryotic 60S ribosomal protein P0 (L10E). The RNA-binding domain and the adjacent domain are thought to exist in archaeal L10 and eukaryotic P0 proteins only.
This domain contains three-stranded and two-stranded anti-parallel β-sheets, located at approximately right angles to each other, and two α-helices between them. It is located on the outer side of the ribosome body between the C-terminal domain of L6, the N-terminal domain of L11, and the H42-H44 region of 23S rRNA [].
The vault complex is the largest ribonucleoprotein particle found in eukaryotes [
]. Although several functions have been proposed for vaults since their discovery in 1986, including roles in multidrug resistance, cell signaling, and innate immunity, their cellular function remains unclear []. In mammals, vaults contain three proteins: the 100kDa major vault protein (MVP), the 193kDa vault poly(ADP-ribosyl)ating polymerase VPARP and the 240kDa telomerase-associated protein TEP1. Approximately 75% of the vault particle mass is due to MVP []. The MVP monomer folds to form structural repeat domains at the N terminus, a shoulder domain, a cap-helix and cap-ring domains.This superfamily represents the major vault protein repeat domain 2, found at the N terminus.
Swi5-dependent recombination DNA repair protein 1 homolog
Type:
Family
Description:
SFR is a component of the SWI5-SFR1 complex, a complex required for double-strand break repair via homologous recombination [
]. It interacts with estrogen receptor alpha and may be a transcriptional modulator for estrogen receptor alpha [].
GATOR complex protein MIO, zinc-ribbon like domain
Type:
Domain
Description:
This entry represents the zinc-ribbon like domain found in the C-terminal of the GATOR complex protein MIOS (also known as WD40 repeat containing protein mio). MIOS is a component of the GATOR2 complex, a complex which positively regulates mTORC1 signalling by acting upstream of or in parallel to GATOR1 [
]. GATOR1 complex is a major negative regulator of the amino acid sensing pathway and its loss causes mTORC1 signalling to be completely insensitive to amino acid starvation [].
Type VI secretion system, RhsGE-associated Vgr protein
Type:
Family
Description:
Type VI secretion system (T6SS) appears to be confined to Proteobacteria. It is important for bacterial pathogenesis, but it is also found in non-pathogenic bacteria, suggesting that T6SS involvement is not limited to virulence [
]. T6SS was identified in Vibrio cholerae [] and Pseudomonas aeruginosa [], and exports Hcp (Haemolysin-Coregulated Protein) and a class of proteins named Vgr (Val-Gly Repeats). In addition to Vgr and Hcp proteins, T6SS is characterised by the presence of an AAA+ Clp-like ATPase and of two additional genes icmF and dotU, encoding homologues of T4SS stabilising proteins []. This entry represent the Vgr family of proteins, associated with some classes of Rhs elements (Rhs classes G and E). Rsh (rearrangement hot-spot) elements are repetitious sequences identified in certain Escherichia coli strains [
,
].
Uncharacterised conserved protein UCP012641, putative zinc-binding metallo-peptidase
Type:
Family
Description:
This family has a highly conserved HHExxH motif with a highly conserved ED pairing downstream. HExxH is indicative of a zinc-binding metallo-peptidase.
This family of proteins includes uncharacterised protein C2orf73 and homologues. Proteins in this family are found in eukaryotes. They are typically between 135 and 289 amino acids in length, with three conserved sequence motifs: GDWWSH, RSDF and KRHG.
This family of proteins is found in eukaryotes. Proteins in this family are typically between 125 and 276 amino acids in length. The family includes OFCC1 (orofacial cleft 1 candidate gene 1 protein), a potentially causal gene for orofacial cleft in humans [
]. However, ablation of the gene had no effects in head development in mice []. Mutations in the homologous Opo gene result in eye malformation in medaka fish [].
Required for respiratory growth protein 8, mitochondrial
Type:
Family
Description:
The function of Rrg8 (required for respiratory growth protein 8) is not clear. It is required for respiratory activity and maintenance and expression of the mitochondrial genome [
]. It is also involved in the plasma membrane electron transport in S. cerevisiae [].
