The Fanconi Anemia (FA) pathway is responsible for interstrand crosslink DNA repair [
]. The name originates the recessive syndrome known as Fanconi anemia, which causes developmental problems and cancer predisposition []. In this pathway, the FANCI-FANCD2 (ID) complex is ubiquitinated by the FA core complex and then travels to sites of damage to coordinate repair [,
]. FA pathway activation seems to trigger dissociation of FANCD2 from FANCI, coinciding with FANCD2 monoubiquitination which precedes monoubiquitination of FANCI []. This suggests a functional separation for FANCD2 from FANCI [].Monoubiquitinated FANCD2 functions to recruit DNA repair factors FAN1 (Fanconi-associated nuclease 1) [
] and SLX4 [], suggesting that chromatin-bound FANCD2Ub is a docking platform for certain DNA repair nucleases. FANCD2 has also a role in replication fork recovery [
].
Transducin beta-like protein 2 (TBL2), also known as WBSCR13, has been linked to Williams-Beuren syndrome [
]. It contains an N-terminal transmembrane region and the C-terminal WD40 domain []. Under endoplasmic reticulum (ER) stress, TBL2 is involved in ATF4 translation through its association with the mRNA [].
The function of Epididymal secretory protein E3-alpha (EDDM3A) and Epididymal secretory protein E3-beta (EDDM3B) is not clear. EDDM3A may function in sperm maturation [
].
ABC transporters belong to the ATP-Binding Cassette (ABC) superfamily, which uses the hydrolysis of ATP to energise diverse biological systems. ABC transporters minimally consist of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These can be found on the same protein or on two different ones. Most ABC transporters function as a dimer and therefore are constituted of four domains, two ABC modules and two TMDs.ABC transporters are involved in the export or import of a wide variety of substrates ranging from small ions to macromolecules. The major function of ABC import systems is to provide essential nutrients to bacteria. They are found only in prokaryotes and their four constitutive domains are usually encoded by independent polypeptides (two ABC proteins and two TMD proteins). Prokaryotic importers require additional extracytoplasmic binding proteins (one or more per systems) for function. In contrast, export systems are involved in the extrusion of noxious substances, the export of extracellular toxins and the targeting of membrane components. They are found in all living organisms and in general the TMD is fused to the ABC module in a variety of combinations. Some eukaryotic exporters encode the four domains on the same polypeptide chain [
].The ABC module (approximately two hundred amino acid residues) is known to bind and hydrolyse ATP, thereby coupling transport to ATP hydrolysis in a large number of biological processes. The cassette is duplicated in several subfamilies. Its primary sequence is highly conserved, displaying a typical phosphate-binding loop: Walker A, and a magnesium binding site: Walker B. Besides these two regions, three other conserved motifs are present in the ABC cassette: the switch region which contains a histidine loop, postulated to polarise the attaching water molecule for hydrolysis, the signature conserved motif (LSGGQ) specific to the ABC transporter, and the Q-motif (between Walker A and the signature), which interacts with the gamma phosphate through a water bond. The Walker A, Walker B, Q-loop and switch region form the nucleotide binding site [
,
,
].The 3D structure of a monomeric ABC module adopts a stubby L-shape with two distinct arms. ArmI (mainly β-strand) contains Walker A and Walker B. The important residues for ATP hydrolysis and/or binding are located in the P-loop. The ATP-binding pocket is located at the extremity of armI. The perpendicular armII contains mostly the alpha helical subdomain with the signature motif. It only seems to be required for structural integrity of the ABC module. ArmII is in direct contact with the TMD. The hinge between armI and armII contains both the histidine loop and the Q-loop, making contact with the gamma phosphate of the ATP molecule. ATP hydrolysis leads to a conformational change that could facilitate ADP release. In the dimer the two ABC cassettes contact each other through hydrophobic interactions at the antiparallel β-sheet of armI by a two-fold axis [
,
,
,
,
,
].The ATP-Binding Cassette (ABC) superfamily forms one of the largest of all protein families with a diversity of physiological functions [
]. Several studies have shown that there is a correlation between the functional characterisation and the phylogenetic classification of the ABC cassette [,
]. More than 50 subfamilies have been described based on a phylogenetic and functional classification [,
,
].This family consists of multi drug resistance-associated protein (MRP) in eukaryotes [
,
,
]. The multidrug resistance-associated protein is an integral membrane protein that causes multidrug resistance when overexpressed in mammalian cells. It belongs to the ABC transporter superfamily. The protein topology and function was experimentally demonstrated by epitope tagging and immunofluorescence. Insertion of tags in the critical regions associated with drug efflux reduced its function. The C-terminal domain seems to be highly conserved.
Chisel protein plays a role in the regulatory network through which muscle cells coordinate their structural and functional states during growth, adaptation, and repair. The X-linked gene Chisel (Csl/Smpx) was first found expressed selectively in human cardiac and skeletal muscle cells []. It is expressed in embryos in sub-regions of the developing heart corresponding to the future chamber myocardium and in developing skeletal muscles []. It is a potential target of the cardiac homeodomain transcription factor Nkx2-5 []. It localises to the costameric cytoskeleton of muscle cells through its association with focal adhesion proteins, where it may participate in regulating the dynamics of actin through the Rac1/p38 kinase pathway [].
This entry represents uncharacterised proteins related to TolQ and other members of the MotA/TolQ/ExbB family. TolQ and TolR have structural and functional homologies not only to ExbB and ExbD of the TonB system, but also with MotA and MotB of the flagellar motor. These three systems are thought to function as ion potential-driven molecular motors [
,
].
MRFAP1 (MORF4 family-associated protein 1) and its interaction partner MORF4L1 (or MRG15) are target proteins of the NEDD8-cullin pathway, which plays an important role in the degradation of cell cycle regulators and transcriptional control networks. It has been suggest that MRFAP1 competes with MRGBP for binding to MORF4L1, thereby regulating MORF4L1 function in chromatin modification [
].
Mutations in CLN6 (ceroid-lipofuscinosis neuronal protein 6) cause variant late-onset neuronal ceroid lipofuscinosis (vLINCL), a childhood neurodegenerative disorder (CLN6). Alterations in neurite maturation resulting from a loss of CLN6 interaction with protein CRMP2, which has been implicated in controlling axon number and outgrowth, may contribute to this neuronal pathology [
]. A link between CLN6 expression and biometal homeostasis has been suggested [].
This entry represents a group of NF-kappa-B inhibitor-interacting Ras-like proteins, known as kappaB-Ras proteins, including KBRS1 and KBRS2 from humans. They are Ras-like proteins that inhibit NF-kappaB transcriptional activity. Despite their high sequence similarity to Ras GTPases, kappaB-Ras proteins contain two Ras oncogenic mutations that drastically reduce GTP hydrolysis [
]. KBRAS1 has been shown to bind IkappaBbeta and regulates cytoplasmic retention of IkappaBbeta/NF-kappaB complexes [,
].
Members of this family include EgtB, and enzyme of the ergothioneine biosynthesis, as found in numerous Actinobacteria [
]. Characterised homologues to this family include a formylglycine-generating enzyme that serves as a maturase for an aerobic sulfatase (cf. the radical SAM enzymes that serve as anaerobic sulfatase maturases).
These small proteins are approximately 100 amino acids in length and appear to be found only in gamma proteobacteria. The function of this protein family is unknown.
This entry represents the cell division protein DamX from Enterobacteriaceae. DamX is an inner membrane protein that contributes to the cell constriction process during bacterial cytokinesis. It contains a C-terminal SPOR domain that may act as autonomous septal targeting determinant [
,
]. DamX localises to the septal ring, but it is non-essential for cell division, and it inhibits cell division when overproduced []. It has been suggested that it may contribute to cell envelope biogenesis or integrity in other ways distinct from its role in cell division [].
This entry represents the cell division protein DedD from Enterobacteriaceae. DedD is an inner membrane protein that contributes to the cell constriction process during bacterial cytokinesis. It contains a C-terminal SPOR domain that may act as autonomous septal targeting determinant [
,
,
].
This family of prion-like proteins has a neuroprotective function, similar to PrP(C)-like [
]. Shadoo is mainly expressed in the brain, and highly expressed in the hippocampus, the area of the brain which co-ordinates memory as well as spatial memory and navigation. This protein may also alter the biological actions of normal and abnormal prion protein (PrP) which lead to lethal neurodegenerative diseases []. This family of proteins is found in eukaryotes. Proteins in this family are approximately 150 amino acids in length, of which the first 90 are alanine rich.
This entry represents Fyv7 (Function required for yeast viability protein 7) from fungi. These proteins are involved in the processing of 20S pre-rRNA during the maturation of SSU-rRNA from tricistronic RNA transcripts (SSU-rRNA, 5.8S rRNA, LSU-rRNA). The SSU (small subunit) processome is required for production of the small ribosomal subunit RNA, the 18S rRNA [
]. Fyv7 may also be required for survival upon K1 Killer toxin exposure.
The expression of the TP53AIP1 (p53-regulated apoptosis-inducing protein 1) protein is induced by wild-type p53. Ectopically expressed TP53AIP1, which is localised within mitochondria, leads to apoptotic cell death through dissipation of mitochondrial A(psi)m. Phosphorylation of p53 Ser-46 regulates the transcriptional activation of TP53AIP1, thereby mediating p53-dependent apoptosis [
].
The tumour suppressor TP53 gene (encoding cellular tumour antigen p53 or p53) is the most frequently altered gene in human tumours. TP53-target gene 5 protein (also known as cellular tumour antigen p53-inducible 5) suppresses cell growth and may play a significant role in p53/TP53-mediating signalling pathway. Its intracellular location and expression change in a cell-cycle-dependent manner [
].
This entry represents the N-terminal domain of the bacterial proteins (PgbA) that bind plasminogen. This activity was identified in In Helicobacter pylori where it is thought to contribute to the virulence of this bacterium. Both PgbA and PgbB are surface-exposed proteins that mediate binding to plasminogen such that it can be converted into plasmin in the presence of a Pg activator [
].
This entry represents the coiled-coil domain-containing protein 7 (also known as BioT2), which is a testis-specific protein found abundantly in five types of murine cancer cell lines. It may play a role in testis development and tumourigenesis [
,
,
].
This entry represents Cdc42 effector protein 2 (also known as Binder of Rho GTPases 1). It is probably involved in the organisation of the actin cytoskeleton [
,
].
Structural domains which comprise this superfamily share the structure of the C-terminal domain (CTD) of the bacterial recombination protein O (RecO), which belongs to the RecF recombination repair pathway involved in replication recovery after DNA damage. It is believed that this CTD acts a a structural scaffold to keep the N-terminal and Zinc-binding domains together. However, because it forms a positively charged grooved with NTD, it is also thought to be involved in DNA binding [
].
Isd proteins are iron-regulated surface proteins found in Bacillus, Staphylococcus and Listeria species and are responsible for haem scavenging from hemoproteins [
]. The IsdB protein is only observed in Staphylococcus and consists of an N-terminal hydrophobic signal sequence, a pair of tandem NEAT (NEAr Transporter, ) domains which confers the ability to bind haem [
] and a C-terminal sortase processing signal which targets the protein to the cell wall. IsdB is believed to make a direct contact with methaemoglobin facilitating transfer of haem to IsdB []. The haem is then transferred to other cell wall-bound NEAT domain proteins such as IsdA and IsdC.
Proteins in this family are required in the final stages of the biosynthesis of secondary metabolite such as fungal alkaloids. These include agroclavine dehydrogenase (easG) from ergot (
Claviceps purpurea), which is required for the biosynthesis of the ergot alkaloid agroclavine, converting the intermediate chanoclavine-I aldehyde to agroclavine non-enzymatically [
,
]; and festuclavine synthase I (ifgF1) from Penicillium roqueforti, which reduces the intermediate 6,8-dimethyl-6,7-didehydroergoline to form festuclavine [
].
This entry represents a relatively rare but broadly distributed uncharacterised protein family, distributed in 1 to 2 percent of bacterial genomes, all of which have outer membranes. In many of these genomes, it is part of a two-gene pair.
Members of this protein family contain two full and two partial repeats of a domain found at the N terminus of Bacillus subtilis cell-division initiation protein DivIVA. The portion repeated four times in these proteins includes the motif GYxxxxVD.
Lipopolysaccharide (LPS) in the outer leaflet of the outer membrane (OM) constitutes the major amphiphilic component of the envelope of most Gram-negative bacteria. This entry represents lipopolysaccharide assembly protein A (LapA) from Gammaproteobacteria. LabA and another heat shock protein, LapB, function together in the assembly of lipopolysaccharide (LPS) [
].
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 [
,
].A number of eukaryotic and archaeal ribosomal proteins have been grouped on the basis of sequence similarities. Ribosomal protein S6 is the major substrate of protein kinases in eukaryotic ribosomes [
] and may play an important role in controlling cell growth and proliferationthrough the selective translation of particular classes of mRNA.This entry represents the archaeal S6 proteins.
RutD is encoded within the Rut operon which allows growth on pyrimidines as sole nitrogen source [
]. The function of this protein is not known, but it is necessary for growth on pyrimidines, and cells lacking RutD produce much less of the Rut pathway intermediate malonic semialdehyde than normal []. It is thought that RutD increases the rate of spontaneous hydrolysis of the toxic intermediate aminoacrylate to malonic semialdehyde.
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 [
,
].A number of eukaryotic and archaeal ribosomal proteins have been grouped
based on sequence similarities []. One of these families, S8e, consists of a number of proteins with either about 220 amino acids (in eukaryotes) or about 125 amino acids (in archaea).This entry represents the archaeal S8e proteins.
Sperm acrosome associated 7 (SPACA7) is expressed only in testis. Its release from the acrosome accelerates the dispersal of cumulus cells surrounding the oocyte and facilitates fertilisation in mice [].
Intraflagellar transport protein 43 (IFT43) is a subunit of the IFT complex A (IFT-A), which is involved in retrograde ciliary transport along microtubules from the ciliary tip to the base [
].
One of the primary rRNA binding proteins, this protein initially binds near the 5'-end of the 23S rRNA. It is important during the early stages of 50S assembly. It makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit and ribosome.
This family of proteins is found in bacteria and are typically between 114 and 143 amino acids in length. There is a conserved KNLFD sequence motif. The annotation with this family suggests that it may be the B subunit of bacterial type IIA DNA topoisomerase but there is no evidence to support this annotation.
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 S13 is one of the proteins from the small ribosomal subunit. In Escherichia coli, S13 is known to be involved in binding fMet-tRNA and, hence, in the initiation of translation. It is a basic protein of 115 to 177 amino-acid residues that contains thee helices and a β-hairpin in the core of the protein, forming a helix-two turns-helix (H2TH) motif, and a non-globular C-terminal extension. This family of ribosomal proteins is present in prokaryotes, eukaryotes and archaea [
].This entry represents archaeal ribosomal S13 proteins.
This entry represents a protein family of unknown function that contains an N-terminal DAK2 domain, so named because of its similarity to the dihydroxyacetone kinase family. Though the function of these proteins is unknown, their presence is strongly correlated with the presence of the GTP-binding protein CgtA, a bacterial GTPase associated with ribosome biogenesis, in certain lineages. This correlation implies some form of functional coupling.
The function of the proteins in this entry is not known, though Atu4866 from Agrobacterium tumefaciens has been structurally characterised. Atu4866 adopts a streptavidin-like fold and has a β-barrel/sandwich which is formed by eight antiparallel β-strands [
]. Atu4866 has a potential ligand-binding site where it has a stretch of conserved residues on the surface.
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 S11 [
] plays an essential role in selecting the correct tRNA in protein biosynthesis. It is located on the large lobe of the small ribosomal subunit. S14 is the eukaryotic homologue of S11; they constitute the uS11 family that includes bacterial, archaeal and eukaryotic proteins [].This entry represents archaeal ribosomal S11 proteins.
This entry consists of nodulation S (NodS) proteins. The products of the rhizobial nodulation genes are involved in the biosynthesis of lipochitin oligosaccharides (LCOs), which are host-specific signal molecules required for nodule formation. NodS is an S-adenosyl-L-methionine (SAM)-dependent methyltransferase involved in N methylation of LCOs. NodS uses N-deacetylated chitooligosaccharides, the products of the NodBC proteins, as its methyl acceptors [
].This entry represents Nodulation protein S found exclusively in bacteria
Senescence-associated protein AAF-like, chlorolplastic
Type:
Family
Description:
This entry represents a group of plant senescence-associated proteins, including AAF from Arabidopsis, SPA15 from Ipomoea batatas (sweet potato) and OSA15 from rice. They are involved in regulating leaf senescence [
,
].
Methyl-CpG-binding domain protein 4 (MBD4) is a mismatch-specific DNA N-glycosylase involved in DNA repair. It has thymine glycosylase activity and is specific for G:T mismatches within methylated and unmethylated CpG sites [
,
].
Methyl-CpG-binding protein 2 (Mecp2) binds specifically to methylated DNA and represses transcription through the recruitment of chromatin remodeling complexes containing histone deacetylase activities [
,
]. It is a multi-functional protein whose function depends on its protein partners and post-translational modifications []. Mecp2 is required for proper mitotic spindle organisation [] and affects proliferation and apoptosis []. Mutations in MeCP2 gene cause an X-linked neurodevelopmental disease known as Rett syndrome [].Methyl-CpG-binding domain protein 4 (MBD4) is a mismatch-specific DNA N-glycosylase involved in DNA repair. It has thymine glycosylase activity and is specific for G:T mismatches within methylated and unmethylated CpG sites [
,
].
Methyl-CpG-binding protein 2 (Mecp2) binds specifically to methylated DNA and represses transcription through the recruitment of chromatin remodeling complexes containing histone deacetylase activities [
,
]. It is a multi-functional protein whose function depends on its protein partners and post-translational modifications []. Mecp2 is required for proper mitotic spindle organisation [] and affects proliferation and apoptosis []. Mutations in MeCP2 gene cause an X-linked neurodevelopmental disease known as Rett syndrome [].
This entry represent a group of plant proteins, including AtDFO from Arabidopsis. AtDFO is a plant-specific protein involved in DNA double-strand break formation during meiosis [
].In flowering plants, gametophyte formation relies on meiosis. In meiosis I, the homologous chromosomes are separated into two daughter cells. In meiosis II, the sister chromosomes are then separated into newly formed daughter cells. During prophase I, several events occurs: sister chromatid cohesion, homologous chromosome synapsis, recombination, crossover formation and chromosome segregation. Homologous recombination is initiated from the formation of DNA double-strand breaks (DSBs). The formation of DSBs is catalyzed by Spo11 and its homologues. So far, six Arabidopsis proteins, AtSPO11-1, AtSPO11-2, AtPRD1, AtPRD2, AtPRD3 and AtDFO, have been shown to be involved in DSB formation [
].
This family consists of functionally uncharacterised proteins predominantly found in archaea, including
from Methanothermobacter thermautotrophicus, which shows an α/β structure.
This family of proteins mainly found in Chlamydiae includes a number of plasmid-encoded virulence proteins, such as Virulence plasmid protein pGP6-D from Chlamydia trachomatis, which seems to be required for growth within mammalian cells [
].
There are currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. They contain multiple conserved cysteine residues, which may indicate metal binding.
This family represents a group of proteins predominantly found in archaea, including UPF0147 protein Ta0600 from Thermoplasma acidophilum
, which shows an all-α structure. Members of this entry are functionally uncharacterised.
This protein family is restricted to the Cyanobacteria, in one or two copies, save for instances in the genus Deinococcus. This protein shows some sequence similarity, especially toward the C terminus, to lipid-A-disaccharide synthase (
or
). The function is unknown.
Chlorosomes are light-harvesting antennae found in green bacteria. This entry represents Chlorosome envelope protein C (CsmC) which is one of the proteins that exists in the chlorosome envelope and has been shown to exist as a homomultimer with CsmD in the chlorosome envelope [
]. CsmC is thought to be important in chlorosome elongation and shape [].
This family of uncharacterised proteins were first identified in the proteome of Treponema pallidum where they are assumed to be secreted proteins because of the presence of putative signal peptides. Homologues are known from other spirochaetes, Elusimicrobia and other bacteria.
This entry represents a group of membrane cofactor proteins (also known as CD46 or TLX). Human CD46 acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue [
]. Rat CD46 may be involved in the fusion of the spermatozoa with the oocyte during fertilization [].
This entry represents UBX domain-containing proteins 2 (Ubx2) and 7 (UBXN7).VCP/p97 or Cdc48 is a eukaryotic ATPase involved in membrane fusion, protein transport, and protein degradation. Ubx2 interacts with Cdc48 in fission yeast [
]. UBXN7 is a ubiquitin-binding adapter that links a subset of NEDD8-associated cullin ring ligases (CRLs) to VCP/p97 to regulate turnover of their ubiquitination substrates [].
UBAP1 (ubiquitin associated protein 1) is a ubiquitin-binding ESCRT-I subunit (endosomal sorting complexes required for transport) [
]. The C-terminal region of UBAP1 is described as a solenoid of overlapping UBAs (SOUBA) which interacts with ubiquitin []. UBAP1-containing ESCRT-I is essential for degradation of antiviral cell-surface proteins.
Beta-glucan synthesis-associated protein Skn1/Kre6/Sbg1
Type:
Family
Description:
This family consists of the beta-glucan synthesis-associated proteins SKN1, KRE6 and Sbg1. Beta1,6-Glucan is a key component of the yeast cell wall, interconnecting cell wall proteins, beta1,3-glucan, and chitin. SKN1 and KRE6 show similarities to glycoside hydrolase family 16 glycoside hydrolases, suggesting that they are glycosyl hydrolases or transglycosylases [
]. Loss of KRE6 shows reduced levels of both beta-1,3-glucan and beta-1,6-glucan synthesis, while loss of SKN1 affects sphingolipid biosynthesis [], being related with the synthesis and anchorage of cell wall proteins of glucan polymers of the yeast cell wall, although they play redundant roles []. SKN1, KRE6 and Sbg1 share the SKN1 domain, which is conserved in SKN1 and KRE6 proteins of many fungal species. Sbg1 is an integral membrane protein essential for contractile-ring constriction and septum formation during cytokinesis, which interacts with the conserved beta-glucan synthase Bgs1 and regulates its protein levels and localisation [,
].
Copper homeostasis protein CutC was originally thought to be involved in copper tolerance in Escherichia coli, as mutation in the corresponding gene lead to an increased copper sensitivity [
]. However, this phenotype has been later reported to depend on the levels of the mRNA-interfering complementary RNA regulator MicL, which is transcribed from a promoter located within the coding sequence of the cutC gene in the enterobacteria []. In the plant pathogen Xylella fastidiosa, this protein has been reported as specific for copper efflux []. The structure of this protein in the bacteria Shigella flexneri showed a monomer structure that adopts a common TIM β/α barrel with 8 β-strands surrounded by 8 α-helices [].The human homologue of this protein, which structure showed a potential copper-binding site, has an important role in intracellular copper homeostasis [
,
].
Irreversible binding of T-even bacteriophages to Escherichia coli is mediated by the short and long tail fibres, which serve as inextensible stays during DNA injection. Short tail fibres are exceptionally stable elongated trimers of gene product 12 (gp12), a 56kDa protein. The N-terminal region of gp12 is important for phage attachment, the central region forms a long shaft, while a C-terminal globular region is implicated in binding to the bacterial lipopolysaccharide core [
]. Long tail fibers consist of a phage-proximal (gp34) and a phage-distal rod, the latter containing two protein trimers (gp36 and gp37). Gp36 is present in the upper part of the distal rod, it forms a complex with gp35 and gp37, binding them through the N-terminal and C-terminal regions, respectively. The upper part of the distal rod has a β-structure [
].
ZapE is a cell division protein found in Gram-negative bacteria. The bacterial cell division process relies on the assembly, positioning, and constriction of FtsZ ring (the so-called Z-ring), a ring-like network that marks the future site of the septum of bacterial cell division. ZapE is a Z-ring associated protein required for cell division under low-oxygen conditions. It is an ATPase that appears at the constricting Z-ring late in cell division. It reduces the stability of FtsZ polymers in the presence of ATP in vitro [
].
Members of this protein family are BoxA, the A component of the BoxAB benzoyl-CoA oxygenase/reductase. This oxygen-requiring enzyme acts in an aerobic pathway of benzoate catabolism via coenzyme A ligation. BoxA is a homodimeric iron-sulphur-flavoprotein and acts as an NADPH-dependent reductase for BoxB [
,
].
Glutamine-binding periplasmic protein GlnH, type 2 periplasmic binding protein fold
Type:
Domain
Description:
GlnH belongs to the type 2 periplasmic-binding fold protein (PBP2) superfamily, whose members are involved in chemotaxis and uptake of nutrients and other small molecules from the extracellular space as a primary receptor [
]. PBP2 typically comprises of two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two receptor cytoplasmically-located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis [
,
].
Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 2, I-BAR domain
Type:
Domain
Description:
Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 2 (Baiap2l2), also known as planar intestinal and kidney specific BAR domain protein (Pinkbar), is an I-BAR (Bin/amphipysin/Rvs) domain containing protein. BAR domain forms an anti-parallel all-helical dimer, with a curved (banana-like) shape, that promotes membrane tubulation. BAR domain proteins can be classified into three types: BAR, F-BAR and I-BAR. BAR and F-BAR proteins generate positive membrane curvature, while I-BAR proteins induce negative curvature [
].In humans Baiap2l2 is specifically expressed in intestinal epithelial cells, where it localises to Rab13-positive vesicles and to the plasma membrane at intercellular junctions [
]. The BAR domain of Baiap2l2 does not induce membrane protrusions or invaginations; instead, it promotes the formation of planar membrane sheets []. This entry represents the N-terminal I-BAR domain, also known as IRSp53/MIM homology Domain (IMD), of Baiap2l2.
Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1, I-BAR domain
Type:
Domain
Description:
Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (Baiap2l1, also known as IRTKS or insulin receptor tyrosine kinase substrate) is an I-BAR (Bin/amphipysin/Rvs) domain containing protein. I-BAR domain is a type of the BAR domain, which forms an anti-parallel all-helical dimer, with a curved (banana-like) shape, that promotes membrane tubulation. The BAR domain containing proteins can be classified into three types: BAR, F-BAR and I-BAR. BAR and F-BAR proteins generate positive membrane curvature, while I-BAR proteins induce negative curvature [].Baiap2l1 binds small GTPase Rac rather than Cdc42 [
]. It serves as an adaptor of the insulin receptor (IR), modulates IR-IRS1-PI3K-AKT signalling via regulating the phosphorylation of IR []. It has been linked to the formation of actin-rich membrane protrusions, called pedestals, during the infection process of enterohemorrhagic Escherichia coli in vertebrates []. This entry represents the N-terminal I-BAR domain, also known as IRSp53/MIM homology Domain (IMD), of Baiap2l1. This domain binds and bundles actin filaments, binds membranes, and interacts with the small GTPase Rac.
Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL), catalytic domain
Type:
Domain
Description:
Biotin and lipoic acid are the covalently bound cofactors of various
multicomponent enzyme complexes that catalyse key metabolic reactions. Inthese enzymes complexes, biotin and lipoic acid are attached via amide linkage
through their carboxyl group and the ε-amino group of a specific lysineresidue of a protein module known respectively as the biotinyl and the lipoyl
domain. Covalent attachment of biotin and lipoic acid tothese enzyme complexes occurs post-translationally, and it is mediated by
biotinylating and lipoylating protein enzymes, which specifically recognisethe biotinyl and lipoyl domains, ensuring their correct post-translational
modification. Lipoylating and biotinylating enzymes are evolutionarily relatedprotein families containing a homologous catalytic module [
].Amino acid sequence conservation between the catalytic modules of biotinyl
protein ligases (BPLs) and lipoyl protein ligases (LPLs) is very low, andmainly affects residues that are important for the scaffold of the structure,
such as those contributing to the hydrophobic core. Despite the poor overallsequence similarity, a single lysine residue is strictly conserved in all LPL
and BPL sequences. This lysine residue is likely to bind specifically to thecarbonyl oxygen of the carboxyl group of biotin or at the end of the hydrogen-
carbon tail of the lipoyl moiety []. The BPL/LPL catalytic domain contains aseven-stranded mixed β-sheet on one side and four α-helices on the
other side [].
Members of this family are part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes. They bind to the proximal sequence element (PSE), a non-TATA-box basal promoter element common to these 2 types of genes. Furthermore, they also recruit TBP and BRF2 to the U6 snRNA TATA box. SNAPc consists of at least four stably associated subunits, SNAP43, SNAP45, SNAP50, and SNAP190. None of the three small subunits can bind to the PSE on their own [
].
Tyrosine-specific protein phosphatase, PTPase domain
Type:
Domain
Description:
This entry represents the PTPase domain found in several tyrosine-specific protein phosphatases (PTPases).Structurally, all known receptor PTPases, are made up of a variable length extracellular domain, followed by a transmembrane region and a C-terminal catalytic cytoplasmic domain. Some of the receptor PTPases contain fibronectin type III (FN-III) repeats, immunoglobulin-like domains, MAM domains or carbonic anhydrase-like domains in their extracellular region. The cytoplasmic region generally contains two copies of the PTPase domain. The first seems to have enzymatic activity, while the second is inactive. The inactive domains of tandem phosphatases can be divided into two classes. Those which bind phosphorylated tyrosine residues may recruit multi-phosphorylated substrates for the adjacent active domains and are more conserved, while the other class have accumulated several variable amino acid substitutions and have a complete loss of tyrosine binding capability. The second class shows a release of evolutionary constraint for the sites around the catalytic centre, which emphasises a difference in function from the first group. There is a region of higher conservation common to both classes, suggesting a new regulatory centre [
]. PTPase domains consist of about 300 amino acids. There are two conserved cysteines, the second one has been shown to be absolutely required for activity. Furthermore, a number of conserved residues in its immediate vicinity have also been shown to be important.Protein tyrosine (pTyr) phosphorylation is a common post-translational modification which can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. Consequently, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase;
) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation [
,
]. The PTP superfamily can be divided into four subfamilies []:(1) pTyr-specific phosphatases(2) dual specificity phosphatases (dTyr and dSer/dThr)(3) Cdc25 phosphatases (dTyr and/or dThr)(4) LMW (low molecular weight) phosphatasesBased on their cellular localisation, PTPases are also classified as:Receptor-like, which are transmembrane receptors that contain PTPase domains [
]
Non-receptor (intracellular) PTPases [
]
All PTPases carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and share a similar core structure made of a central parallel β-sheet with flanking α-helices containing a β-loop-α-loop that encompasses the PTP signature motif [
]. Functional diversity between PTPases is endowed by regulatory domains and subunits.
This entry represents the coiled-coil α-helical rod protein 1 (HCR) from animals. The function of HCR is unknown but it has been implicated in psoriasis in humans and is thought to affect keratinocyte proliferation [
].
This entry represents cytochrome c-type biogenesis protein CcmB (HelB) from bacteria and plants.CcmB is the product of one of a cluster of ccm genes that are necessary for cytochrome c biosynthesis in bacteria and is required for the export of haem to the periplasm [
]. Plant mitochondria have kept a cytochrome c biogenesis pathway inherited from their prokaryote ancestor and also have a CcmB homologue, but in plants the ccm genes are distributed between the nuclear and the mitochondrial genomes instead of being coded in a single operon [,
].
This entry represents a group of eukaryotic transmembrane proteins, including mannose-P-dolichol utilization defect 1 protein [
] and solute carrier family 66 member 3 (SLC66A3).
