Members of this family contain a regulatory ACT domain with an additional N-terminal extension of ~70 aa, and therefore may be a stand-alone regulatory protein. Some members of the family have previously been annotated as chorismate mutases, but this is erroneous [
].
There are currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Though the N-terminal half of these proteins is related to the N-terminal half of steroid delta-isomerase, the C-terminal half is predicted to be structurally unrelated. Both halves of the latter protein contain key active site residues (Tyr14, Asp99) [
] that are missing from the proteins in this group.
This entry represents a group of proteins that regularly co-occur in genomes, typically as gene pairs, with members of
, a probable FMN-dependent member of the bacterial luciferase-like monooxygenase (LLM) family. At least one member, RF|YP_001509627.1 from Frankia sp. EAN1pec, is fused to the LLM protein. The function of these gene pairs is unknown, but members in this entry are annotated as oxidoreductases and NADPH-dependent FMN reductases.
Cysteine desulphuration protein SufE participates in cysteine desulphuration mediated by SufS. Cysteine desulphuration mobilizes sulphur from L-cysteine to yield L-alanine and constitutes an essential step in sulphur metabolism for biosynthesis of a variety of sulphur-containing biomolecules. SufE functions as a sulphur acceptor for sufS, by mediating the direct transfer of the sulphur atom from the S-sulphanylcysteine of sufS, an intermediate product of cysteine desulphuration process [
,
,
].
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 [
,
].Ribosomal protein S8 is one of the proteins from the small ribosomal subunit. In Escherichia coli, S8 is known to bind
directly to 16S ribosomal RNA. It belongs to a family of ribosomal proteins which, on the basis of sequencesimilarities, groups eubacterial, algal and plant chloroplast, cyanelle, archaebacterial and
Marchantia polymorpha mitochondrial S8; mammalian and plant S15A; and yeast S22 (S24) ribosomal proteins.
This entry represents a group of plant proteins, including GEX3 from Arabidopsis. GEX3 is essential for micropylar pollen tube guidance and plays a role during early embryogenesis [
].
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 [
,
].The small subunits of bacterial and eukaryotic ribosomes have the same overall shapes (with structural elements described as head, body, platform, beak and shoulder). Ribosomal protein S6 is one of the proteins from the small ribosomal subunit. [
]. In Escherichia coli, S6 is known to bind together with S18 to 16S ribosomal RNA. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups bacterial, red algal chloroplast and cyanelle S6 ribosomal proteins.
Acyl-CoA-binding protein (ACBP) is a small (10 Kd) protein that binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters [
]. ACBP is also known as diazepam binding inhibitor (DBI) or endozepine (EP) because of its ability to displace diazepam from the benzodiazepine (BZD) recognition site located on the GABA type A receptor. It is therefore possible that this protein also acts as a neuropeptide to modulate the action of the GABA receptor [].ACBP is a highly conserved protein of about 90 residues that is found in all four eukaryotic kingdoms, Animalia, Plantae, Fungi and Protista, and in some eubacterial species [
].Although ACBP occurs as a completely independent protein, intact ACB domains have been identified in a number of large, multifunctional proteins in a variety of eukaryotic species. These include large membrane-associated proteins with N-terminal ACB domains, multifunctional enzymes with both ACB and peroxisomal enoyl-CoA Delta(3), Delta(2)-enoyl-CoA isomerase domains, and proteins with both an ACB domain and ankyrin repeats (
) [
].The ACB domain consists of four α-helices arranged in a bowl shape with a
highly exposed acyl-CoA-binding site. The ligand is boundthrough specific interactions with residues on the protein, most notably
several conserved positive charges that interact with the phosphate group onthe adenosine-3'phosphate moiety, and the acyl chain is sandwiched between the
hydrophobic surfaces of CoA and the protein [].Other proteins containing an ACB domain include:
Endozepine-like peptide (ELP) (gene DBIL5) from mouse [
]. ELP is a testis-specific ACBP homologue that may be involved in the energy metabolism of the mature sperm.MA-DBI, a transmembrane protein of unknown function which has been found in
mammals. MA-DBI contains a N-terminal ACB domain.DRS-1 [
], a human protein of unknown function that contains a N-terminal ACB domain and a C-terminal enoyl-CoA isomerase/hydratase domain.
DNA damage-binding protein 2 (DDB2) is required for DNA repair. It binds to DDB1 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair [
]. It is also involved in the initiation of nucleotide excision repair via an ubiquitin ligase complex together with DDB1 and CUL4A (cullin 4A) [].
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 [
,
].Ribosomal protein L36 is the smallest protein from the large subunit of the prokaryotic ribosome. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities can be grouped into: bacterial L36; algal and plant chloroplast L36; Cyanelle L36. L36 is a small basic and cysteine-rich protein of 37 amino-acid residues.
This entry represents ribosomal protein L19 from eukaryotes, as well as L19e from archaea [
]. L19/L19e is part of the large ribosomal subunit, whose structure has been determined in a number of eukaryotic and archaeal species [].
This rare conserved hypothetical protein of small size occurs exclusively, and perhaps universally, in the context of a pair of (uncharacterised) radical SAM proteins, HxsC (
) and HxsB (
). Many members of this family have invariant motifs LYW and LLNDYxLRE, but PSI-BLAST starting from family members well below 20% pairwise sequence identity to this group eventually brings in the entire family as modeled here. The CHP03979 family (
) represents the fourth regularly conserved member of this system [
].
CURVATURE THYLAKOID 1 (CURT1) protein family is conserved in plants and cyanobacteria. There are four Arabidopsis CURT1 proteins, CURT1A, B, C, and D. They can modify thylakoid architecture by inducing membrane curvature [
].
This domain is found in the autophagy-related proteins ATG17 and ATG11, conserved across eukaryotes [
,
]. ATG17 forms a complex with ATG29 and ATG31, critical for both PAS (preautophagosomal structure) formation and autophagy. Together with ATG13, it is required for ATG1 kinase activation [, CITE:23219485]]. ATG11 is a scaffold protein required for the cytoplasm-to-vacuole targeting (Cvt) pathway during starvation and to recruit ATG proteins to the pre-autophagosome. It is also required for ATG1 kinase activation. In many eukaryotes, ATG11 (the orthologue in mammals is RB1-inducible coiled-coil protein 1 (RB1CC1) and in S. pombe is Taz1-interacting factor 1 (taf1)) is essential for bulk autophagy, except in S.cerevisiae []. ATG17 and ATG11 are large similar proteins, both predicted to be almost entirely helical, containing conserved coiled-coil regions and lack obvious functional motifs [,
].
This entry corresponds to the capsid protein found in the Ty3 transposons of yeast as well as other transposable elements present in eukaryotes [
,
]. These long terminal repeat (LTR) retrotransposons share similarities with the envelope protein in retroviruses like HIV-1 [].
Glycosylphosphatidylinositol-anchored merozoite surface protein
Type:
Family
Description:
This family of proteins represents the core region of Bd37, a surface antigen of B.divergens which is GPI-anchored at the surface of the merozoite. The structure of the protein consists of mainly alpha folds and has three sub domains [
].
This entry represents a group of putative transport accessory proteins, including MmpS1-5 from Mycobacterium tuberculosis [
]. They are part of an export system required for biosynthesis and secretion of siderophores, and are essential for virulence of Mycobacterium tuberculosis []. MmpS4 possesses an N-terminal transmembrane (TM) helix and a C-terminal soluble domain [].
Coiled-coil-helix-coiled-coil-helix domain-containing protein 1
Type:
Family
Description:
CHCHD1, originally known as C2360, is a member of a novel protein family with a conserved coiled coil-helix-coiled coil-helix domain [
]. It is a mitochondrial ribosomal protein with a role in mitochondrial protein synthesis [].
Inner membrane-spanning protein YciB (also known as intracellular septation protein A) is a family of proteins which are essential for both normal cell division and bacterial virulence and are believed to play a role in the septation process [
,
]. These proteins play a role in cell envelope biogenesis, maintenance of cell envelope integrity and membrane homeostasis [,
,
,
].
PcG proteins form large multiprotein complexes (PcG bodies) which are involved in the stable repression of genes involved in development, signaling or cancer via chromatin-based epigenetic modifications. Mammalian PRC1 includes canonical (cPRC1) and non-canonical complexes; cPRC1, contains four core subunits including one CBX protein (CBX2, CBX4, and CBX6-CBX8) that binds H3K27me3. CBX family members have different affinity for H3K27me3, with CBX7 having the highest binding capability [
,
].This entry represents CBX7 [
]. In pluripotent cells, CBX7 is the main PRC1-associated Cbx protein and plays an important role in the maintenance of pluripotency [].
This entry includes WBP-1 and its homologous. WBP-1 is a ligand of the WW domain of Yes-associated protein. This protein has a proline-rich domain. WBP-1 does not bind to the SH3 domain [
]. This entry also includes transmembrane protein 92 (TMEM92), whose function is not clear.
This family consists of several Rhizobium FixH like proteins. It has been suggested that the four proteins FixG, FixH, FixI, and FixS may participate in a membrane-bound complex coupling the FixI cation pump with a redox process catalysed by FixG [].
Members of this family usually are small proteins (PatC, TenC, TruC) of unknown function in cyanobactin (prenylated cyclic peptide) biosynthesis clusters, where a different small protein is a known cyanobactin precursor (patellamide, anacyclamide, piricyclamide, etc). They may instead be the C-terminal domain of a longer protein that otherwise consists mostly of lectin-like or VWF type A domains, in similar context. Similar to the cyanobactin precursors, members of this family have two very strongly conserved regions separated by a hypervariable region, suggesting these proteins may undergo a similar maturation [
].
This superfamily represents the N-terminal domain of pre-hexon-linking protein IIIa.The major capsid protein of the adenovirus strain is also known as a hexon. This entry represents protein IIIa, which is a hexon-associated protein that is likely to participate in vertex stabilisation and genome packaging. It stabilises vertices by tethering the penton bases to neighbouring peripentonal hexons, and lashes peripentonal hexons to the neighbouring hexons through its interaction with hexon-linking protein. During virus assembly, it seems to play a role in packaging of viral DNA via its interaction with packaging protein 3 [
,
].
Replication gene A proteins (also known as GpA) are found in bacteriophages and in bacteria as part of a suspected prophage. These proteins function as endonucleases during DNA replication [
,
,
].
This family consists of several proteobacterial phosphonate metabolism protein (PhnI) sequences. Bacteria that use phosphonates as a phosphorus source must be able to break the stable carbon-phosphorus bond. In Escherichia coli phosphonates are broken down by a C-P lyase that has a broad substrate specificity. The genes for phosphonate uptake and degradation in E. coli are organised in an operon of 14 genes, named phnC to phnP. Three gene products (PhnC, PhnD and PhnE) comprise a binding protein-dependent phosphonate transporter, which also transports phosphate, phosphite, and certain phosphate esters such as phosphoserine; two gene products (PhnF and PhnO) may have a role in gene regulation; and nine gene products (PhnG, PhnH, PhnI, PhnJ, PhnK, PhnL, PhnM, PhnN, and PhnP) probably comprise a membrane-associated C-P lyase enzyme complex [
].
The DNA terminal protein Gp3, found in a number of Bacillus phages, is linked to the 5' ends of both strands of the genome through a phosphodiester bond between the β-hydroxyl group of a serine residue and the 5'-phosphate of the terminal deoxyadenylate. This protein is essential for DNA replication and is involved in the priming of DNA elongation [
].
DotA is essential for intracellular growth in Legionella [
]. DotA is thought to play an important role in regulating initial phagosome trafficking decisions either upon or immediately after macrophage uptake [].
This entry contains BRRF2 from Epstein-Barr virus. This protein family is restricted to the herpesviruses; it's function is not known. The protein is phosphorylated and is associated with the viral tegument [
].
Tail virion protein 7P (G7P) is a viral transmembrane protein that interacts with the packaging signal of the viral genome leading to the initiation the virion concomitant assembly-budding process in the host inner membrane [
]. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
Intraflagellar transport (IFT) is the bidirectional movement of multimeric protein particles, termed IFT particles, between the cell body and the distal tip of a flagellum. IFT particle proteins are thought to serve as scaffolds to facilitate the attachment of cargo proteins to IFT motors, mediating the transport of flagellar precursors [
]. The main constituents of IFT particles are organized into two protein complexes, A and B.IFT25 is a component of the intraflagellar transport (IFT) complex B. It directly interacts with IFT27, forming a subcomplex that may be involved in the regulation of IFT [
,
]. IFT25 is required for Hedgehog signalling in cilia [].
CEP89 is a component of the distal appendages of centrioles, and is required for ciliogenesis [
]. CEP89 has also been shown to be required for mitochondrial metabolism and neuronal and cognitive function [].
Meiosis 1 arrest protein (M1AP), also known as spermatogenesis-associated protein 37 (Spata37), is required for meiosis I progression during spermatogenesis [].
BEND3 is a transcriptional repressor that associates with the nucleolar-remodeling complex (NoRC) and is involved in ribosomal DNA (rDNA) silencing [
]. SUMOylated BEND3 stabilizes the NoRC component Tip5 via USP21 deubiquitinase []. NorC serves as a molecular platform that recruits chromatin modifiers, such as histone deacetylases and histone methyltransferases, leading to deacetylation of histone H4 and trimethylation of H3K9 and H4K20 []. NoRC also targets histone deacetylases and histone methyltransferases to rDNA to establish a heterochromatic state that inhibits transcription activation. Hence, BEND3 and NoRC seem to play a concerted role in the maintenance of heterochromatin architecture [,
].BEND3 has also been shown to mediate Polycomb recruitment in the absence of H3K9Me3 or DNA methylation at the pericentromeric regions [
]. BEND3 interacts with PICH (ERCC6L), a DNA translocase required for the maintenance of chromosome stability, and stimulates its translocase and ATPase activities. This interaction occurs via an interface between a TPR domain in PICH and a BEN domain in BEND3 [].
TA0956 is a protein from Thermoplasma acidophilum which currently has no known function however the structure has been determined. The protein has a two-layered alpha/β-sandwich topology and is a putative Elongation factor 1-alpha binding motif [].
This family consists of several eukaryotic extracellular matrix protein 1 (ECM1) sequences. ECM1 has been shown to regulate endochondral bone formation, stimulate the proliferation of endothelial cells and induce angiogenesis [
,
]. Mutations in the ECM1 gene can cause lipoid proteinosis, a disorder which causes generalised thickening of skin, mucosae and certain viscera. Classical features include beaded eyelid papules and laryngeal infiltration leading to hoarseness [].
MAP7 (also known as E-MAP-115 or Ensconsin) is a microtubule-stabilising protein that may play an important role in microtubule reorganisation during polarisation and differentiation of epithelial cells [
]. It may play a role in the formation of intercellular contacts [,
].The MAP7 family has three other members: MAP7 domain containing proteins 1 (MAP7D1), 2 (MAP7D2) and 3 (MAP7D3) [
]. MAP7D3 has been identified as a critical regulator of microtubule stability, probably through its binding to tubulin and microtubules, as well as its regulation of histone deacetylase 6 activity [,
].
Omp28 is a 28kDa outer membrane protein from Porphyromonas gingivalis. Omp28 is thought to be a surface adhesion/receptor protein. Omp28 is expressed in a wide distribution of P.gingivalis strains [
].
Copper resistance protein K (CopK) is a periplasmic dimeric protein which is strongly up-regulated in the presence of copper, leading to a high periplasmic accumulation [
,
]. CopK has two different binding sites for Cu(I), each with a different affinity for the metal. Binding of the first Cu(I) ion (CuI) induces a conformational change of CopK which involves dissociation of the dimeric apo-protein. Binding of a second Cu(I) (CuII) further increases the plasticity of the protein. The binding of CuI greatly enhances the specific affinity for CuII and, in turn, CuII binding increases the specific affinity for CuI, although to a lesser extent. This type of cooperative behaviour is unprecedented in copper binding proteins []. CopK has features that are common with functionally related proteins such as a structure consisting of an all-beta fold and a methionine-rich Cu(I) binding site [].
This family consists of archaeal GvpO proteins which are required for gas vesicle synthesis [
]. The family also contain related sequences from bacteria.
This entry represents the central region of protein UNC80 from eukaryotes, a component of the NALCN sodium channel complex. NALCN is a cation voltage-independent channel activated by substance P, neurotensin, acetylcholine and noradrenaline that controls neuronal excitability. UNC80 forms a complex with UNC79 and both are key regulators of the channel and required for the proper expression and axonal localisation of NALCN. UNC80 is required for NALCN control by GPCRs and essential for its sensitivity to extracellular calcium. This protein acts as a scaffold for Src family of tyrosine kinases (SFK) and UNC-79 to mediate interaction with NALCN [
,
,
]. Proteins containing this domain also include some uncharacterised proteins from fungi.
FlhG (also annotated FleN/YlxH) is an ATPase that regulates location and number of bacterial flagella [
,
,
,
]. FlhG acts antagonistically with FlhF/FleQ to regulate the number of polar flagella, with FlhF promoting flagellar assembly and FlhG inhibiting it. FlhG interacts with FlhF and influences its GTPase activity [,
].FlhG and FlhF are responsible for generating the single polar flagellum of Pseudomonas sps and Vibrio cholerae. In these bacteria, FlhG represses the activity or expression of a master transcriptional regulator [
], FleQ in the case of Pseudomonas [,
]. Campylobacter jejuni FlhG likely influences a flagellar biosynthetic step to control flagellar number, rather than suppressing activators of flagellar gene transcription as in Vibrio and Pseudomonas species []. On the peritrichous bacterium Bacillus subtilis, FlhF and FlhG function together to spatially organize flagella in a defined grid-like pattern around the cellular midpoint, but not at polar regions [].
The N-terminal region of the the PH1510 protein (1510-N or PH1510-N) from archaebacterium Pyrococcus horikoshii has been shown to possess serine protease activity and has a Ser-Lys catalytic dyad, preferentially cleaving hydrophobic substrates. It is structurally related to ClpP. In the genome of Pyrococcus horikoshii, PH1510 is homologous to the genes nfed (nodulation formation efficiency D) [
].PH1510 (MEROPS identifier S49.005) is thought to be a signal peptide peptidase, which degrades the membrane-bound signal peptide after it has been released from secreted proteins [
]. The peptidase domain is followed by a C-terminal NfeD domain [].
This entry represents a subset of proteins from the Bric-a-Brac/Tramtrack/Broad Complex (BTB) family predominantly found in the plant class Magnoliopsida, including POB1 from Arabidopsis. BTB proteins direct the selective ubiquitylation of proteins following their assembly into Cullin3-based ubiquitin ligases. Proteins in this family contain a BTB (broad complex/tramtrack/bric-a-brac, also known as poxvirus and zinc finger (POZ) domain and a BACK (BTB-and-C-terminal-Kelch) domain [,
].POB1 (also known as light-response BTB2, Lrb2) is predicted to be involved in ubiquitination [
,
] and to negatively regulate the ABA-mediated inhibition of germination [].
Fatty acid binding proteins (FABPs) and cellular
retinoic-acid-binding proteins (CRBPs) are part of the intracellular-lipid-binding proteins (iLBPs) family [].The primary role of all the FABP members is regulation of fatty acid uptake and intracellular transport [
]. To date, nine FABPs have been identified in mammals, each showing specific tissue distribution patterns and ligand preference. All FABP members have a similar β-barrel structure; fatty acid ligands are accommodated in the central cavity of the β-barrel, which dramatically increases their solubility in the aqueous cytoplasm, facilitating their movement to target sites [,
].Retinoic-acid-binding proteins (CRBPs) are specific for vitamin A derivatives and can be classified into the cellular retinoic acid-binding proteins (CRABP-I and II) and the cellular retinol-binding proteins (CRBP-I, II, III, and IV) [
].
Members of this family are annotated as tetratricopeptide repeat protein 38. The function is not known. Proteins containing tetratricopeptide (TPR) repeats may indicate mostly α-helical secondary structure.
UNC93B1 is a multi-transmembrane domain-containing protein that plays an essential role in signalling by the nucleotide-sensing Toll-like receptors (TLRs), including TLR3, TLR7 and TLR9 [
,
]. UNC93B1 delivers the nucleotide-sensing receptors TLR7 and TLR9 from the ER to endolysosomes []. It has been shown to recruit Syntenin-1 and dampen TLR7 signalling and prevent autoimmunity []. It also binds TLR9, and the release of TLR9 from UNC93B1 is required for TLR9 to function []. Mutations in the UNC93B1 gene that result in aberrant TLR trafficking can lead to autoimmune disease [].
This presumed domain is found in bacteria. This domain is about 180 amino acids in length, its function is unclear. This domain is found at the C-terminal of
.
This entry represents the mitochondrial dynamics protein MID49/MID51. Most members of this protein family contain a Mab-21 domain and are found in chordates.In humans, MID49 and MID51 are outer membrane proteins involved in the regulation of mitochondrial organisation and required for mitochondrial fission by promoting the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface independently of the mitochondrial fission FIS1 and MFF proteins. They also regulate DNM1L GTPase activity [
,
,
,
,
]. Deregulation of these proteins has been linked to human diseases such as pulmonary arterial hypertension [].
This domain is found in large proline-rich protein BAG6 protein. It has a conserved SDL sequence motif. Human BAG6 is an ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins [
]. It functions as part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, which maintains these client proteins in a soluble state and participates to their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation [,
,
,
].
This protein family is predominantly found in cyanobacteria and includes PII-interacting protein X (PipX) from Synechococcus elongatus. PipX modulates the expression of genes involved in nitrogen assimilation by interacting with the global nitrogen transcription factor NtcA and the signal transduction protein PII. It is involved in several regulatory pathways [
,
]. The crystal structure of this protein shows a tudor-like domain (TLD), formed by a highly bent β-sheet that mediates the interactions with both PII and NtcA, and two C-terminal helices [].
This entry represents the C-terminal domain of ribosomal protein L5. 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 [
,
].Ribosomal protein L5, ~180 amino acids in length, is one of the proteins from the large ribosomal subunit. In Escherichia coli, L5 is known to be involved in binding 5S RNA to the large ribosomal subunit. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities [
,
,
], groups:Eubacterial L5.Algal chloroplast L5.Cyanelle L5.Archaebacterial L5.Mammalian L11.Tetrahymena thermophila L21.Dictyostelium discoideum (Slime mold) L5Saccharomyces cerevisiae (Baker's yeast) L16 (39A).Plant mitochondrial L5.
Bacterial type IV pili are critical surface appendages involved in diverse biological processes including horizontal gene transfer, surface and host cell adhesion, biofilm formation, colonization, twitching and virulence. These pili extend and retract from the cell surface, requiring the action of an extension ATPase, often called PilB, and a retraction ATPase PilT, respectively [
]. PilT depolymerizes the pilus fibre and recycles pilin subunits into the inner membrane. Many type IVa pilus systems also have a homologue of the retraction ATPase PilT, called PilU, which promotes type IV pilus retraction in a PilT-dependent manner through its ATPase activity. PilT and PilU are required for twitching motility and form independent homo-hexamers, which directly interact. PilU is important for generating maximal retraction forces [,
]. Members of this family may be found in some species that do not have type IV pili but have related structures for DNA uptake and natural transformation.
This entry represents the L50 protein from the mitochondrial 39S ribosomal subunit. L50 appears to be a secondary RNA-binding protein [
]. The 39S ribosomal protein appears to be a subunit of one of the larger mitochondrial 66S or 70S units []. Under conditions of ethanol-stress in rats the larger subunit is largely dissociated into its smaller components [].
Rtt102 (Regulator of Ty1 Transposition Protein 102) is a component of both the SWI/SNF and the RSC chromatin remodelling complexes [
]. RSC complex is involved in transcription regulation and nucleosome positioning and is responsible for the transfer of a histone octamer from a nucleosome core particle to naked DNA [
]. SWI/SNF complex is an ATP-dependent chromatin-remodelling complex required for the positive and negative regulation of gene expression of a large number of genes. It changes chromatin structure by altering DNA-histone contacts within a nucleosome, leading eventually to a change in nucleosome position, thus facilitating or repressing binding of gene-specific transcription factors [,
].
This entry represents Zinc finger protein 532 and related proteins from animals. Most members of this family contain several Zinc-finger C2H2-type domains. ZN532 is thought to be involved in transcriptional regulation.
This entry represents a group of fork-head domain-containing proteins, including the transcriptional activators FOXJ2/3 from humans.In humans FOXJ2 has two isoforms, FHX.L and FHX.S. FHX. L can bind to two different type of DNA binding sites. The levels of FOXJ2 expression have been linked to a variety of cancers [
,
,
,
,
]. The expression of FOXJ3 is associated with cancers and rheumatoid arthritis [,
].In mice FOXJ2 is involved in the regulation of meiosis during spermatogenesis [
].
This entry includes DcaP which is the most abundant outer membrane channel protein in Acinetobacter baumannii. X-ray crystallography reveals a trimeric porin-like structure and suggests dicarboxylic acids as potential substrates [
].
Prokaryotic and eukaryotic organisms respond to heat shock or other environmental stress by inducing the synthesis of proteins collectively known
as heat-shock proteins (hsp) []. Amongst them is a family of proteins with an average molecular weight of 20 Kd, known as the hsp20 proteins [,
,
]. These seem to act as chaperones that can protect other proteins against heat-induced denaturation and aggregation. Hsp20 proteins seem to form large heterooligomeric aggregates.Structurally, this family is characterised by the presence of a conserved C-terminal domain of about 100 residues. This family also includes the related alpha-crystallin (alphaC) protein [
].
This family includes the tail tubular Gp11 protein from bacteriophage T7. In Podoviridae the virus tail is attached to the head through the tail adaptor protein. The location of Gp11 in the tail, together with its oligomerization change upon assembly (between monomer and dodecamer), suggests that Gp11 could act as an adaptor protein [
].
This family includes several DNA encapsidation protein sequences from the phi-29-like viruses (gene product 16, Gp16). Gp16 is the primary ATPase of the motor assembly of phi-29; it binds to the prohead RNA to form a pentameric ring to complete the assembly of the DNA packaging motor [
,
,
]. The characteristics of the protein distribution suggest prophage matches.
Oxidase ustYa is involved in the the production of ustiloxins, toxic cyclic peptides, in fungi. Ustiloxins were found to be the first example of cyclic peptidyl secondary metabolites that are ribosomally synthesized in filamentous fungi. The homologous genes ustYa and ustYb (which are found in the gene cluster for ustiloxins) have been shown to be involved in cyclization of the peptide [
,
,
].Other proteins in this entry include cyclochlorotine biosynthesis proteins O, P and R from
Talaromyces islandicuswhich are encoded within a cluster of genes required for biosynthesis of the mycotoxin cyclochlorotine. CccP is probably the phenylalanine aminomutase that provides the unusual beta-Phe amino acid, but the roles of the other proteins are unknown [
].
TnpM enhances the Tn21 transposition by activating expression of the transposase gene and decreases the resolution of the cointegrated DNA by suppressing expression of the resolvase gene [
].
This is the C-terminal domain of Chordin-like proteins 1 and 2 (CHRDL1/2). CHRDL1 antagonizes the function of BMP4 by binding to it and preventing its interaction with receptors [
]. CHRDL2 inhibit bone morphogenetic proteins (BMPs) activity by blocking their interaction with their receptor []. CHRDL2 may play a role during myoblast and osteoblast differentiation and maturation []. It's worth noting that there are different results regarding its binding partners; according to [], CHRDL2 interacts with INHBA but not BMP2, BMP4 and BMP6.
FlhB and its functionally equivalent orthologues, from among a larger superfamily of proteins involved in type III protein export systems, are involved in flagellar protein export [
]. Proteins in this entry play roles specifically related to flagellar structures [].
This entry includes XPF from animals, Rad1 from budding yeasts and Rad16 from fission yeasts. Human XPF is a catalytic component of a structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair. It is involved in homologous recombination that assists in removing interstrand cross-link [
]. Budding yeast Rad1 and Rad10 form an endonuclease that specifically degrades single-stranded DNA [].
Tsi2 is an essential protein in Pseudomonas aeruginosa, providing protection from the activity of Tse2, most likely by directly interacting with Tse2 [
]. Tse2 is a toxin transported via the type VI secretion system and is targeted towards other bacteria in the environment [].
This entry represents the Probable solute-binding protein AdeT1/2 from Acinetobacter baumannii. These proteins are involved in resistance to antibiotics by active efflux [
]. Members of this protein family are found mostly in Proteobacteria.
Interestingly, primate lineage LRTOMT has two alternative reading frames and encodes two different protein (LRTOMT1 and LRTOMT2), which exist as separate genes (Lrrc51 and Tomt) in rodents. Mutations of LRTOMT cause nonsyndromic deafness in humans [
]. This entry represents LRTOMT1 (or Lrrc51). The function of LRTOMT1 is not clear.
Glyoxalase domain-containing protein 4 (GLOD4) contains the vicinal oxygen chelate (VOC) domain. The function of GLOD4 is not clear. The C. elegans member in this entry, known as glyoxalase 1 or CeGly, has been shown to be involved in the MG modifications of mitochondrial proteins and mitochondrial ROS production [
].
Doublecortin domain-containing protein 1 (DCDC1), also known as DCDC5, is a member of doublecortin (DCX) family. It is a microtubule-associated protein (MAP) with stable double tandem DCX repeats of ubiquitin-like tertiary fold. DCDC1 is expressed during mitosis and is involved in coordinating late cytokinesis. DCDC1 interacts with cytoplasmic dynein and Rab8, as well as with the Rab8 nucleotide exchange factor Rabin8 [
].
The small Ras-like GTPase Ran plays an essential role in the transport of macromolecules in and out of the nucleus and has been implicated in spindle and nuclear envelope formation during mitosis in higher eukaryotes. The Saccharomyces cerevisiae ORF YGL164c encoding a novel RanGTP-binding protein, termed Yrb30p was identified. The protein competes with S. cerevisiae RanBP1 (Yrb1p) for binding to the GTP-bound form of S. cerevisiae Ran (Gsp1p) and is, like Yrb1p, able to form trimeric complexes with RanGTP and some of the karyopherins [
].
This family consists of several virulence-associated proteins, mainly from Corynebacterium equii (Rhodococcus equi, Rhodococcus hoagii). R. equi is an important pulmonary pathogen of foals and is increasingly isolated from pneumonic infections and other infections in Homo sapiens immunodeficiency virus-infected patients. Both virulent and avirulent strains of R. equi differ in the possession of a virulence-associated plasmid [
]. The type of virulence plasmid carried is host specific; the pVapA is the plasmid type carried by R. equi isolates infecting equine. These virulence plasmids have four common regions known as the conjugation, replication, unknown function and the virulence or pathogenicity island (PAI) regions, where the members of the vap (virulence associated protein) family reside [,
]. The virulence protein VapA has been shown to inhibit the maturation of R. equi-containing phagosomes and promote intracellular bacterial survival [].
This family consists of several different short Staphylococcal proteins known as the phenol-soluble modulin beta proteins, including SLUSH A, B and C proteins as well as haemolysin and gonococcal growth inhibitor [
]. Some strains of the coagulase-negative Staphylococcus lugdunensis produce a synergistic hemolytic activity (SLUSH), phenotypically similar to the delta-hemolysin of S. aureus [,
]. Gonococcal growth inhibitor from Staphylococcus acts on the cytoplasmic membrane of the gonococcal cell causing cytoplasmic leakage and, eventually, death [].
Synaptonemal complex protein 1 (SYCP1) is the major component of the transverse filaments of the synaptonemal complex. Synaptonemal complexes are structures that are formed between homologous chromosomes during meiotic prophase [
].
This sclerostin family consists of sclerostin and sclerostin domain-containing protein 1. Sclerostin (SOST) is thought to suppress bone formation. Mutations of the SOST gene lead to sclerosteosis, a progressive sclerosing bone dysplasia with an autosomal recessive mode of inheritance. Radiologically, it is characterised by a generalised hyperostosis and sclerosis leading to a markedly thickened and sclerotic skull, with mandible, ribs, clavicles and all long bones also being affected. Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur. Sclerosteosis is clinically and radiologically very similar to van Buchem disease, mainly differentiated by hand malformations and a large stature in sclerosteosis patients [
]. Sclerostin domain-containing protein 1, also known as USAG1, is a bone morphogenetic protein antagonist [].
Deubiquitinating protein VCPIP1, also known as VCIP135, is required for the p97/p47 and p97/p37 pathways and is involved in Golgi and ER membrane fusion. It reverses ubiquitination events that occurs during mitotic disassembly, regulating Golgi membrane dynamics during mitosis. This entry represents the N-terminal domain that interacts with WAC (the WW domain-containing adaptor with coiled coil). This interaction increases the deubiquitinating activity of VCPIP1 and is necessary for p97/p47-mediated Golgi membrane fusion [,
].
This small family of proteins is currently restricted to Methanosarcina species. Members of this family are about 200 residues in length, except for
that has two copies of this region. Although the function of this region is unknown the pattern of conservation suggests that this may be an enzyme, including multiple conserved aspartate and glutamate residues. The most conserved motif in these proteins is NEL/MEXNE/D, where X can be any amino acid, and is found at the C terminus of these proteins.
This entry includes GpX protein from Bacteriophage P2. GpX is a phage tail protein [
]. Sequence analysis suggests that they are related to which suggests a general peptidoglycan binding function.
This entry also includes uncharacterised bacterial proteins.
Developing Dictyostelium (Slime mold) cells form large aggregation streams that break up into groups of cells. Each group then becomes a fruiting body. Cells sense if there are too many cells in a stream by sensing the concentration of counting factor (CF), a protein complex secreted by the aggregating cells [
]. This entry includes counting factor-associated protein A/B/C from Slime mold.
