CFAP300 is a cilia- and flagella-associated protein that is essential for assembly of dynein arms. Mutations in the CFAP300 gene (C11orf70) cause defective cilia motility and primary ciliary dyskinesia [
,
].
This entry describes a set of polysaccharide biosynthesis/export proteins. Members are variable in either containing or lacking a 78-residue insert, but appear to fall within a single clade. The genomic context of these genes also include genes that encode components of the PEP-CTERM/EpsH (exosortase) protein sorting system.
PiggyBac transposable element-derived protein 5 (PGBD5) is a DNA transposase that mediates PGBD5-induced DNA rearrangements in rhabdoid tumour cells [
]. It can induce genomic rearrangements that inactivate the HPRT1 gene [].
Prophet of Pit-1 (Prop1) is a homeodomain transcription factor involved in morphogenesis, apoptosis and proliferation in the developing pituitary, and in pituitary organogenesis including the differentiation of cell lineages [
,
].
Sequences in this family of proteins are members of the chain length determinant family (
) which includes the wzc protein from Escherichia coli. This family of proteins are homologous to the EpsF protein of the methanolan biosynthesis operon of Methylobacillus sp. 12S [
]. The distribution of this protein appears to be restricted to a subset of exopolysaccharide operons containing a syntenic grouping of genes including a variant of the EpsH exosortase protein. Exosortase has been proposed to be involved in the targeting and processing of proteins containing the PEP-CTERM domain to the exopolysaccharide layer.
Conserved hypothetical protein CHP03016, PEP-CTERM
Type:
Family
Description:
Members of this protein family are found predominantly in exopolysaccharide biosynthesis operons marked by the presence of the EpsH-family putative exosortase and presence in the genome of the PEP-CTERM protein sorting signal. Members of this family may be distantly related to the EpsL family (
).
Dual specificity/tyrosine protein phosphatase, N-terminal
Type:
Domain
Description:
The active core of the dual specificity protein phosphatase is made up of two globular domains both with the DSP-like fold. These domains are arranged in tandem, and are associated via an extensive interface to form a single globular whole. The conserved PTP signature motif (Cys-[X]5-Arg) that defines the catalytic centre of all PTP-family members is located within the C-terminal domain, DSPc (
). Although the centre of the catalytic site is formed from DSPc, two loops from the N-terminal domain, DSPn, also contribute to the catalytic site, facilitating peptide substrate specificity [
].This domain represents the N-terminal half of the core (DSPn).
DNA excision repair protein Rad28/ERCC8/Ckn1/ATCSA-1
Type:
Family
Description:
This entry represents a group of DNA excision repair proteins, including Rad28 from budding yeasts [
], Ckn1 from fission yeasts, ATCSA-1 from Arabidopsis [] and ERCC8 (also known as CSA) from animals []. Ckn1 is involved in transcription-coupled nucleotide excision repair []. Human CSA is part of a E3-ubiquitin ligase (E3-ub ligase) complex and plays an important part in transcription-coupled repair (TCR)[]. In Arabidopsis, ATCSA-1 is a critical component for initiating the repair of UV-B-induced DNA lesions [].Mutations in the CSA gene cause Cockayne syndrome A (CSA), a rare disorder characterised by cutaneous sensitivity to sunlight, abnormal and slow growth, cachectic dwarfism, progeroid appearance, progressive pigmentary retinopathy and sensorineural deafness [
].
ZapA is a cell division protein which interacts with FtsZ. FtsZ is part of a mid-cell cytokinetic structure termed the Z-ring that recruits a hierarchy of fission related proteins early in the bacterial cell cycle. The interaction of FtsZ with ZapA drives its polymerisation and promotes FtsZ filament bundling thereby contributing to the spatio-temporal tuning of the Z-ring [
].The structure of ZapA is organised into two distinct domains, with the first 49 residues forming a globular domain comprised of a two stranded antiparallel β-sheet and an α-helix, whereas the C-terminal half of the protein (residues 50-102) forms a single, 14-turn α-helix. The ZapA protomer forms a pseudosymmetric tetramer.This superfamily represents a domain found at the N terminus of the cell division protein ZapA. Its structure is composed of an α-helix which plays a role in mediating ZapA-FtsZ interactions to facilitate FtsZ filament bundling and Z-ring stability in dividing bacterial cells.
Fanconi anemia-associated protein of 100kDa (FAAP100) is component of the Fanconi anemia (FA) core complex, which plays a central role in FA-associated DNA damage response. FAAP100 is essential for the stability and function of the complex [
].Fanconi anemia (FA) is a human disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinks and other damages. The FA complex repairs the interstrand cross-linking (ICL) lesions and coordinates activities of the downstream DNA repair pathway including nucleotide excision repair, translesion synthesis, and homologous recombination. It is required for the monoubiquitylation of FANCD2 and FANCI heterodimer. The FA core complex consists of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, FANCM, FANCT (UBET2), FAAP100 and FAAP24 [
,
].
Members of this superfamily are involved in mitochondrial biogenesis and G2/M phase cell cycle progression. They form a component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins [
].
This family of proteins is found in eukaryotes. Proteins in this family are typically between 95 and 154 amino acids in length. This family includes human C15orf61.
This entry represents a predicted spore germination protein GerPD. They are required for the formation of functionally normal spores. They could be involved in the establishment of normal spore coat structure and/or permeability, which allows the access of germinants to their receptor [
].
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 [,
,
].FtsE is an ABC transporter ATP-binding protein. This protein and its permease partner FtsX, localize to the cell division
site. In a number of species, the ftsEX gene pair is located next to ftsY, which encodes the signal recognition particle-docking protein.
This family consists of multidrug resistance ATP binding cassette (ABC) transporters from fungi. This family includes PDR10 and PDR15, members of the pleiotropic drug resistance (PDR) network in Saccharomyces cerevisiae [
], and CDR transporters from Candida albicans [,
,
]. The ABC transporter family is a group of membrane proteins that use the hydrolysis of ATP to power the translocation of a wide variety of substrates across cellular membranes. ABC transporters minimally consist of two conserved regions: a highly conserved nucleotide-binding domain (NBD) and a less conserved transmembrane domain (TMD). Eukaryotic ABC proteins are usually organised either as full transporters (containing two NBDs and two TMDs), or as half transporters (containing one NBD and one TMD), that have to form homo- or heterodimers in order to constitute a functional protein [
].
C8orf37 encodes a ciliary protein known as CFAP418. In humans, mutations in C8orf37 cause two types of retinal dystrophies: cone-rod dystrophy type 16 (CORD16) and retinitis pigmentosa type 64 (RP64). CORD16 affects the cone receptors which detect red, green or blue wavelengths of light, and RP64 affects the cone receptors first and then the rod receptors. Both of these affect the photo-receptors in the eye leading to colour blindness or blindness respectively [
].
This family of proteins is found in eukaryotes. Proteins in this family are typically between 238 and 363 amino acids in length. There are two conserved sequence motifs: EYP and KCTPD.
This group represents the cyclin-dependent kinase 2-associated protein 1/2 (DOC-1/1R). DOC-1 is a specific inhibitor of the cell-cycle kinase CDK2 [
]. DOC-1R associates with CDK2 and inhibits CDK2 activation by obstructing its association with cyclin E and A [].
Members of this group are known as retinoic acid early inducible proteins (RAE-1) [
,
]. They are ligands for the activating immunoreceptor NKG2D, which is widely expressed on natural killer cells, T cells, and macrophages []. There is a considerable diversity of NKG2D ligands. In mice, the ligands include, among others, five members of the retinoic acid early inducible gene 1 (RAE-1; α-ε) [].RAE-1 proteins are distant major histocompatibility complex (MHC) class I homologues, comprising isolated alpha1-alpha2 platform domains [
].
Tfx has an N-terminal basic domain with a helix-turn-helix motif for DNA binding and a C-terminal acidic domain possibly for transcriptional activation [
]. This is the C-terminal region of Tfx-like DNA-binding proteins.
This entry represents protein MENT (methylated in normal thymocytes protein), which is involved in control of cellular proliferation. It is an onconcogenic modifier contributing to the tumour suppressor function of DNMT3B (DNA methyltransferase 3B) [
]. This entry also includes the mouse Pmis1 protein that may regulate sperm transport into the oviducts and function in modulating sperm-zona binding [].
This entry represents a group of eukaryotic proteins that are typically between 161 and 229 amino acids in length. There is a single completely conserved residue F that may be functionally important.
This entry represents a group of homeobox proteins, including Tlx1/2/3. They are transcription factors that belong to the to the Hox11 family. In general, they bind to the DNA sequence 5'-CGGTAATTGG-3' [
]. Tlx1 and Tlx3 are required for fate determination of glutamatergic and GABAergic neurons in the dorsal spinal cord [,
]. Tlx1, also known as Hox11, is required to maintain normal Wt1 mRNA levels in the developing spleen in mice []. Tlx2, also known as Ncx/Hox11L.1, is required for the adequate development of enteric neurons in mice [].
The ScdA protein was originally identified as a cell wall biosynthesis protein since mutations in the scdA gene produce cell walls with highly aberrant morphology [
]. Subsequent studies have shown that ScdA belongs to the wider Repairs of iron centres (RIC) family and is a di-iron protein that, amongst other functions, protects the cell from damage caused by exposure to nitric oxide and to hydrogen peroxide [,
].
YtfE was is also known as regulator of cell morphogenesis and NO signaling because it is involved in anaerobic NO protection [
]. It is part of a family of di-iron proteins involved in the repair of iron-sulphur clusters [,
].
This family consists of several outer membrane proteins (2a and 2b) from Brucella abortus.
B. abortus is Gram-negative, facultative intracellular bacteria that can infect many species of animalsand Homo sapiens [
].
HarA (also known as isdH) is a haem-binding NEAT-domain (NEAr Transporter,
) protein which has been shown to bind to the haptoglobin-hemoglobin complex in order to extract haem from it. HarA has also been reported to bind haemoglobin directly [
]. HarA (also known as IsdH) contains three NEAT domains as well as a sortase A C-terminal signal for localisation to the cell wall. The haem bound at the third of these NEAT domains has been shown to be transferred to the IsdA protein also localised at the cell wall, presumably through an additional specific protein-protein interaction []. Haptoglobin is a haemoglobin carrier protein involved in scavenging haemoglobin in the blood following red blood cell lysis and targetting it to the liver.
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. It has been shown that IsdA and IsdB co-localise within the Staphylococcal cell wall to discrete sites corresponding to regions of hemoglobin capture [].
This family consists of several uncharacterised Streptomyces proteins as well as one from
Mycobacterium tuberculosis. The function of these proteins isunknown.
Antitermination proteins positively regulate expression of bacteriophage early and late gene operons [
]. Bacterial host RNA polymerase is modified by these antitermination proteins to a terminator-resistant form that transcribes through termination sites that would otherwise prevent expression of the regulated genes.Enterobacteria phage lambda antitermination protein N is essential for the expression of two phage early operons which are critical for phage development. This entry represents the RNA-binding arginine-rich motif (also known as N36) which forms a complex with boxB RNA by binding tightly to the major groove of the boxB hairpin via hydrophobic and electrostatic interactions forming a bent alpha helix [
].
Members of this protein family are identified as the substrate-binding protein of a urea ABC transport system by similarity to a known urea transporter from Corynebacterium glutamicum, operon structure, proximity of its operons to urease (urea-utilization protein) operons, and by Partial Phylogenetic Profiling vs. urea utilisation.
Neuronal migration protein doublecortin (DCX; also known as Lissencephalin-X) seems to be required for the initial steps of neuronal dispersion and cortex lamination during cerebral cortex development [
]. This protein may act by competing with the putative neuronal protein kinase DCAMKL1 in binding to a target protein, and thereby participate in a signalling pathway that is crucial for neuronal interaction before and during migration, possibly as part of a calcium ion-dependent signal transduction pathway. It may also be involved with LIS-1 in an overlapping, but distinct, signalling pathways that promotes neuronal migration. Defects in neuronal migration protein doublecortin are the cause of lissencephaly X-linked type 1 (LISX1), a classic lissencephaly characterised by mental retardation and seizures that are more severe in male patients [
,
].This family represents the neuronal migration protein doublecortin found in chordates.
R1 is a gene for resistance to late blight, the most destructive disease in potato cultivation worldwide. The R1 gene belongs to the class of plant genes for pathogen resistance that have a leucine zipper motif, a putative nucleotide binding domain and a leucine-rich repeat domain [
]. Most proteins matching this entry are found associated with NB-ARC domain .
Sep1/2 is related to the chlorophyll a/b-binding gene family members. The transcripts of Sep1 and Sep2 were present under low light conditions, but their level increased 4- to 10-fold during illumination of plants with high-intensity light [
].
This entry represents a group of plant proteins, including PTAC10 from Arabidopsis. PTAC10 is a component of the PEP (plastid-encoded RNA polymerase) complex, which transcribes photosynthesis-related genes and plastid tRNAs during later developmental stages [
,
]. PTAC10 contains a single S1 RNA-binding domain. PTAC10 knock-out lines have been shown to display an albino phenotype and impaired chloroplast development. PTAC10 is essential for plastid gene expression in Arabidopsis and can be phosphorylated by cpCK2. Phosphorylation of pTAC10 could enhance its RNA-binding activity [].
This entry represents a group of eukaryotic proteins that are typically between 170 and 183 amino acids in length. In humans, the gene encoding this protein lies in the position, chromosome 15 open reading frame 52.
SUV2 (SENSITIVE TO UV 2) is a putative plant ATRIP homologue that is a component of the ATR-dependent cell checkpoint response [
]. The suv2 mutant is defective in cell-cycle arrest in response to DNA damage [].
Protein TRACHEARY ELEMENT DIFFERENTIATION-RELATED 6/7
Type:
Family
Description:
This entry represents a group of plant proteins, including Protein TRACHEARY ELEMENT DIFFERENTIATION-RELATED 6 and 7 (TED6/7) from Arabidopsis. They are involved in the secondary cell wall formation of vessel elements [
].
YjeF N-terminal domain-containing protein NAXE-like
Type:
Family
Description:
This entry represents a subgroup of the YjeF N-terminal domain-containing proteins from eukaryotes, bacteria and archaea, including NAXE and YJEFN3 from humans [
]. NAXE is an NAD(P)H-hydrate epimerase that has been shown to regulate cholesterol efflux from endothelial cells []. YJEFN3 may play a role in spermiogenesis and oogenesis [].In bacteria or archaea, YjeF N-terminal domains are often fused to a YjeF C-terminal domain [
]. It is a bifunctional enzyme that catalyses the epimerisation of the S- and R-forms of NAD(P)HX and the dehydration of the S-form of NAD(P)HX at the expense of ADP, which is converted to AMP []. However, this entry represents the subgroup that only contain the YjeF N-terminal domain. The reduced forms of NAD and NADP, two major nucleotides playing a central role in metabolism, are continuously damaged by enzymatic or heat-dependent hydration. Eukaryotic NAD(P)H-hydrate epimerase catalyses the epimerisation of the S- and R-forms of NAD(P)HX, the damaged form of NAD(P)H. This is a prerequisite for the S-specific NAD(P)H-hydrate dehydratase to allow the repair of both epimers of NAD(P)HX [
]. This family also includes yeast YNL200C, which is a NAD(P)H-hydrate epimerase that catalyses the epimerisation of the S- and R-forms of NAD(P)HX, at the expense of ATP, which is converted to ADP [
]. In Arabidopsis, AtPPOX (At5g49970) or PDX3, a fusion protein with the YjeF N-terminal domain and a C-terminal domain that functions as a pyridoxine/pyridoxamine 5'-phosphate oxidase, has been identified. AtPPOX is involved in the vitamin B6 salvage pathway [
].
Coiled-coil domain-containing protein 50, N-terminal
Type:
Domain
Description:
This entry represents the N-terminal domain of the coiled-coil domain-containing protein 50 (CCDC50). Human CCDC50 is overexpressed in mantle cell lymphoma and chronic lymphocytic leukemia. Its involvement in NFkappaB signalling pathways may have major effects on cell survival [
].
The reovirus inner capsid protein lambda-1 displays nucleoside triphosphate phosphohydrolase (NTPase), RNA-5'-triphosphatase (RTPase), and RNA helicase activity and may play a role in the transcription of the virus genome, the unwinding or reannealing of double-stranded RNA during RNA synthesis. The RTPase activity constitutes the first step in the capping of RNA, resulting in a 5'-diphosphorylated RNA plus-strand. Lambda1 is an Orthoreovirus core protein, VP3 is the homologous core protein in Aquareoviruses [
,
,
].
Speedy (Spy1, also known as RINGO A) is a cell cycle regulatory protein which binds and activates CDK1 and CDK2 [
], protein kinases that allows progression through G1/S phase and further replication events. Spy1 activates CDK2 inducing a conformational change of the CDK2 T-loop that avoids its phosphorylation []. Spy1 expression overcomes a p27-induced cell cycle arrest to allow for DNA synthesis, so cell cycle progression occurs due to an interaction between Spy1 and p27 [].
Kelch-like protein 30 (KLHL30) belongs to the KLHL family [
]. Its function is not clear.The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].
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 superfamily represents a subdomain of the ribosomal protein S8e found exclusively in eukaryotes. This domain consists of 3 helices.
The Adenoviruses nucleoprotein core consists of genomic dsDNA and six proteins. Protein V is one of the most important proteins in the core due to its involvement in core condensation. Protein V also bridges the viral DNA core with the outer capsid by interacting with protein VI. It plays an important role in capsid assembly and in the formation of infectious virions [
,
].
The bacteriophage T7 tail complex consists of a conical tail-tube surrounded by six kinked tail-fibres, which are oligomers of the viral protein gp17. The tail spike protein of bacteriophage K1F is important for the initial absorption of the phage into its host bacterium by hydrolysing the alpha-sialosyl linkages in the polysialic acid capsule [
].
Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL)
Type:
Homologous_superfamily
Description:
This superfamily represents the fold comprising the seven β-strands found in the catalytic domain of Class II of aminoacyl-tRNA synthetases (aaRS), the lipoyl protein ligase (LPL) and the biotinyl protein ligase (BPL), which structurally homologous [
]. Interestingly, Class II of aaRSs has a two-step reaction mechanism analogous to that of BPL. It first catalyses the ATP-dependent formation of an aminoacyl-AMP intermediate and then transfer the activated aminoacyl moiety to an acceptor tRNA [].The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [
,
]. These proteins differ widely in size and oligomeric state, and have limited sequence homology []. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric []. Class II aminoacyl-tRNA synthetases share an antiparallel β-sheet fold flanked by α-helices [], and are mostly dimeric or multimeric, containing at least three conserved regions [,
,
]. However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [].BPLs and LPLs are evolutionarily related protein families, with a homologous catalytic module (seven-stranded mixed β-sheet on one side and four α-helices on the other side) that must have evolved from a common ancestor [
,
]. Amino acid sequence conservation between the catalytic modules of biotinyl protein ligases (BPLs) and lipoyl protein ligases (LPLs) is very low, and mainly affects residues that are important for the scaffold of the structure, such as those contributing to the hydrophobic core. Despite the poor overall sequence similarity, a single lysine residue is strictly conserved in all LPL and BPL sequences. This lysine residue is likely to bind specifically to the carbonyl oxygen of the carboxyl group of biotin or at the end of the hydrogen-carbon tail of the lipoyl moiety [].
RNA polymerase II-associated protein 1, N-terminal
Type:
Domain
Description:
Inhibition of RNA polymerase II-associated protein 1 (RPAP1) synthesis in Saccharomyces cerevisiae (Baker's yeast) results in changes in global gene expression that are similar to those caused by the loss of the RNAPII subunit Rpb11 [
]. This entry represents the N-terminal region of RPAP-1 that is conserved from yeast to humans.
RNA polymerase II-associated protein 1, C-terminal
Type:
Domain
Description:
Inhibition of RNA polymerase II-associated protein 1 (RPAP1) synthesis in Saccharomyces cerevisiae (Baker's yeast) results in changes in global gene expression that are similar to those caused by the loss of the RNAPII subunit Rpb11 [
]. This entry represents the C-terminal region that contains the motif GLHHH. This region is conserved from yeast to humans.
Arp2/3 binds to pre-existing actin filaments and nucleates new daughter filaments, and thus becomes incorporated into the dynamic actin network at the leading edge of motile cells and other actin-based protrusive structures [
]. The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility []. In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. It promotes homologous recombination (HR) repair in response to DNA damage, leading to drive motility of double-strand breaks (DSBs) []. In order to nucleate filaments, Arp2/3 must bind to a member of the N-WASp/SCAR family protein []. Arp2 and Arp3 are thought to be brought together after activation, forming an actin-like nucleus for actin monomers to bind and create a new actin filament. In the absence of an activating protein, Arp2/3 shows very little nucleation activity. Recent research has focused on the binding and hydrolysis of ATP by Arp2 and Arp3 [], and crystal structures of the Arp2/3 complex have been solved [].The human complex consists of Arp2/3 complex composed of ARP2, ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC. This family represents the ARPC3/p21-ARC subunit.
In budding yeast, Get4 is part of the GET complex that inserts the tail-anchored (TA) proteins into the endoplasmic reticulum membrane [
,
]. In humans, Get4 is part the BAG6/BAT3 complex, maintains misfolded and hydrophobic patches-containing proteins in a soluble state and facilitates their proper delivery to the endoplasmic reticulum, or alternatively promotes their sorting to the proteasome where they undergo degradation [,
,
,
]. The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane [,
,
].
Mre11 and Rad50 are two proteins required for DNA repair and meiosis-specific double-strand break formation in Saccharomyces cerevisiae. Mre11 by itself has 3' to 5' exonuclease activity that is increased when Mre11 is in a complex with Rad50 [
]. These eukaryotic proteins contain one metallo-phosphoesterase domain followed by an Mre11 DNA-binding domain. S. cerevisiae Mre11 is required for DNA repair and meiosis-specific
double-strand break (DSB) formation [] and has both 3' to 5' exonuclease activity (whichincreases when in complex with Rad50) and endonuclease activity. The N-terminal phosphoesterase domain is
required for DSB repair, and the carboxyl-terminal dsDNA-binding domain is essential during meiosis forchromatin modification and DSB formation [
]. Schizosaccharomyces pombe rad32 is required for repair of double strand breaks and recombination [].
Cmc1 is a metallo-chaperone like protein which is known to localise to the inner mitochondrial membrane in Saccharomyces cerevisiae. It is essential for full expression of cytochrome c oxidase and respiration [
]. Cmc1 contains two Cx9C motifs and is able to bind copper(I). Cmc1 is thought to play a role in mitochondrial copper trafficking and transfer to cytochrome c oxidase.
Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product.PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane [
,
,
]. Within the core of the complex, the chlorophyll and beta-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection []. This family represents the low molecular weight phosphoprotein PsbH found in PSII. The phosphorylation site of PsbH is located in the N terminus, where reversible phosphorylation is light-dependent and redox-controlled. PsbH is necessary for the photoprotection of PSII, being required for: (1) the rapid degradation of photodamaged D1 core protein to prevent further oxidative damage to the PSII core, and (2) the insertion of newly synthesised D1 protein into the thylakoid membrane [
]. PsbH may also regulate the transfer of electrons from D2 (Qa) to D1 (Qb) in the reaction core.
ER membrane protein complex subunit 1 is a component of the ER membrane protein complex (EMC, composed of EMC1, EMC2, EMC3, EMC4, EMC5 and EMC6). In Saccharomyces cerevisiae, the EMC seems to be required for efficient folding of proteins in the endoplasmic reticulum (ER) [
].
RNA-polymerase II-associated protein 3-like, C-terminal domain
Type:
Domain
Description:
This domain is found at the C terminus of the RNA-polymerase II-associated protein 3 (RPAP3). RPAP3 binds to Monad and is involved in regulating apoptosis [
]. This domain represents the potential Monad-binding region of RPAP3. RPAP3 contains TPR-repeats towards the N terminus. This domain is also found in other proteins with TPR-repeats at the N terminus, like sperm-associated antigen 1 [], and in proteins without TPR-repeats.
Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product.PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane [
,
,
]. Within the core of the complex, the chlorophyll and beta-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection []. This family represents the intrinsic antenna protein CP43 (PsbC), which is one of two such proteins found in the reaction centre of PSII, both of which can bind to chlorophyll 'a' and beta-carotene, passing the excitation energy on to the reaction centre [
].
Uncharacterised conserved protein UCP030333, DNA/RNA-binding Alba-related
Type:
Family
Description:
There is currently no experimental data for members of this group. However, the proteins are distantly related to the archaeal DNA/RNA-binding protein Alba, also called histone-like protein (
), and its eukaryotic homologues RNase P/MRP subunits Pop7/Rpp20 (
) and Rpp25. Therefore, members of this group can be predicted to be involved in RNA and/or DNA binding.
Structural comparisons have shown that Alba (Sso10b2 from the thermoacidophilic archaeon Sulfolobus solfataricus) is topologically similar to several RNA-binding proteins (or A-DNA-binding) and includes IF3-C, YhhP, and DNase I. All of them have a similar IF3-C fold [
,
] and it has been suggested that the ancestral function of the IF3-C fold is related to RNA interaction, and that the Alba superfamily proteins originated as RNA-binding proteins that formed various ribonucleoprotein complexes, probably including RNase P, and were then recruited as a chromosomal protein within the crenarchaeal lineage []. Based on this, it has been suggested that the archaeal Alba proteins () are involved in RNA binding as well as DNA binding [
,
], a prediction that has been confirmed experimentally [].For more information about Alba, please see
.
These sequences are derived from a number of hypothetical plant proteins. The region in question is approximately 270 amino acids long. Some members of this family are annotated as yeast pheromone receptor proteins AR781 but no literature was found to support this.
This entry include human Golgi pH regulators (GPHR) and GPCR-type G proteins (GTG1 and GTG2) from Arabidopsis. GTG1 and GTG2 may function both as a new type of G protein and as a class of membrane-localized ABA receptors in Arabidopsis [
].Human Golgi pH regulator A (GPR89A) and Golgi pH regulator B (GPR89B) exhibit a voltage-dependent anion-channel activity that may function in counterion conductance [
].
This family represents U3 small nucleolar RNA-associated protein 25 (UTP25), a DEAD-box RNA helicase-like protein component of the ribosomal small subunit processome for the biogenesis of ribosomes, which functions in pre-ribosomal RNA (pre-rRNA) processing. U3 small nucleolar RNA-associated protein 25 homologue (also known as Digestive organ expansion factor (DEF)) from animals is essential for embryonic development in part through the regulation of p53 pathway and controls the expansion growth of digestive organs and liver [
,
,
]. It is though to be also involved in the sympathetic neuronal development. UTP25 mediates, with CAPN3, the proteasome-independent degradation of p53/TP53 [,
].Protein NUCLEOLAR FACTOR 1 from Arabidopsis thaliana (Nof1) is also included in this group. This protein is involved in the control of rRNA expression, embryo development and female gametogenesis [
].
Ribosomal protein S27, zinc-binding domain superfamily
Type:
Homologous_superfamily
Description:
This superfamily represents a domain found in the zinc-binding ribosomal protein S27e. It consists of a β-sandwich of two three-stranded sheets. This a novel fold due to the uniqueness of the strands arrangement [
].
Putative membrane protein insertion efficiency factor
Type:
Family
Description:
This family consists of hypothetical membrane protein insertion efficiency factor proteins. They contain three conserved
cysteine residues. They may be involved in insertion of integral membrane proteins into the membrane [].
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].This entry represents the eukaryotic 60S ribosomal protein L18a [
] and L20 [] from eukaryotes. Rat ribosomal protein L18 is homologous to Xenopus laevis L14 [].
Translation elongation factor EF1B/ribosomal protein S6
Type:
Homologous_superfamily
Description:
An alpha+beta sandwich domain with a Ferredoxin-like fold can be found in the beta chain of the translation elongation factor EF1B [
], and in the ribosomal protein S6 from the small subunit [].Elongation factor EF1B (also known as EF-Ts or EF-1beta/gamma/delta) is a nucleotide exchange factor that is required to regenerate EF1A from its inactive form (EF1A-GDP) to its active form (EF1A-GTP). EF1A is then ready to interact with a new aminoacyl-tRNA to begin the cycle again. EF1B is more complex in eukaryotes than in bacteria, and can consist of three subunits: EF1B-alpha (or EF-1beta), EF1B-gamma (or EF-1gamma) and EF1B-beta (or EF-1delta) [
].
Ribosomal protein L30, ferredoxin-like fold domain
Type:
Domain
Description:
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].Ribosomal protein L30 is one of the proteins from the large ribosomal subunit. L30 belongs to a family of ribosomal proteins which, on the basis of sequence similarities [
], groups bacteria and archaea L30, yeast mitochondrial L33, and Drosophila melanogaster, Dictyostelium discoideum (Slime mold), fungal and mammalian L7 ribosomal proteins. L30 from bacteria are small proteins of about 60 residues, those from archaea are proteins of about 150 residues, and eukaryotic L7 are proteins of about 250 to 270 residues. L30 is missing in some groups of bacteria, such as the CPR group, the PVC group, Cyanobacteria, and some symbionts, which suggests that it is non-essential [,
].This entry represents a domain with a ferredoxin-like fold, with a core structure consisting of core: beta-α-β-α-β. This domain is found in prokaryotic ribosomal protein L30 (short-chain member of the family), as well as in archaeal L30 (L30a) (long-chain member of the family), the later containing an additional C-terminal (sub)domain. It is also found in nucleolar proteins with similarity to large ribosomal subunit L7 proteins. These are constituents of 66S pre-ribosomal particles and play an essential role in processing of precursors to the large ribosomal subunit RNAs [
,
,
].
DNA replication in eukaryotes results from a highly coordinated interaction between proteins, often as part of protein complexes, and the DNA template. One of the key early steps leading to DNA replication is formation of the prereplication complex, or pre-RC. The pre-RC is formed by the sequential binding of the origin recognition complex (ORC), Cdc6 and Cdt1 proteins, and the MCM complex. Activation of the pre-RC into the initiation complex (IC) is achieved via the action of S-phase kinases, eventually leading to the loading of the replication machinery.Recently, a novel replication complex, GINS (for Go, Ichi, Nii, and San; five, one, two, and three in Japanese), has been identified [
,
]. The precise function of GINS is not known. However, genetic and two-hybrid interactions indicate that it mediates the loading of the enzymatic replication machinery at a step after the action of the S-phase kinases [
]. Furthermore, GINS may be a part of the replication machinery itself, since it is found associated with replicating DNA [,
]. Electron microscopy of GINS shows that it forms a ring-like structure [], reminiscent of the structure of PCNA [], the DNA polymerase delta replication clamp.This observation, coupled with the observed interactions for GINS, indicates that the complex may represent the replication clamp for DNA polymerase epsilon [].The GINS complex is essential for initiation of DNA replication in Xenopus egg extracts [
]. This 100kDa stable complex includes Sld5, Psf1, Psf2, and Psf3. Homologues of these components are found also in other eukaryotes. This family of proteins represents the Psf2 component.
PDCD2 is localized predominantly in the cytosol of cells situated at the opposite pole of the germinal centre from the centroblasts as well as in cells in the mantle zone. It has been shown to interact with BCL6, an evolutionarily conserved Kruppel-type zinc finger protein that functions as a strong transcriptional repressor and is required for germinal centre development. The rat homologue, Rp8, is associated with programmed cell death in thymocytes.
This entry includes TMEM85 from mammals and Emc4 from budding yeasts. They inhibit hydrogen peroxide mediated cell death in yeast [
]. Emc4 is part of the ER membrane complex (EMC) that may play a role in protein folding [].
Many members of this family have no known function and are predicted to be integral membrane proteins.One member of the family has been characterised as protein PGR (AtPGR). PGR is suggested to be a potential glucose-responsive regulator in carbohydrate metabolism in plants. This entry also includes protein VTE6, which is a Pphytyl-phosphate kinase catalyzing the conversion of phytyl-monophosphate to phytyl-diphosphate [
].
Nuclear pore localisation protein NPL4, C-terminal
Type:
Domain
Description:
The HRD4 gene is identical to NPL4, a gene previously implicated in nuclear transport. Using a diverse set of substrates and direct ubiquitination assays, analysis revealed that HRD4/NPL4 is required for a poorly characterised step in ER-associated degradation following ubiquitination of target proteins but preceding their recognition by the 26S proteasome [
]. Npl4p physically associates with Cdc48p via Ufd1p to form a Cdc48p-Ufd1p-Npl4p complex. The Cdc48-Ufd1-Npl4 complex functions in the recognition of several polyubiquitin-tagged proteins and facilitates their presentation to the 26S proteasome for processive degradation or even more specific processing [].
