Members of this protein family are probable NAD-dependent dehydrogenases related to the alanine dehydrogenase of Archaeoglobus fulgidus (see
) [
] and, more distantly, to ornithine cyclodeaminase. Members include the staphylobactin biosynthesis protein SbnB. Together with SbnA, SbnB is encoded by the staphyloferrin B biosynthetic gene cluster. SbnA uses PLP and substrates O-phospho-L-serine and L-glutamate to produce a metabolite N-(1-amino-1-carboxyl-2-ethyl)-glutamic acid (ACEGA), while SbnB uses NAD(+) to oxidatively hydrolyze ACEGA to yield alpha-ketoglutarate and L-Dap [].
This entry represents mitochondrial ribosomal protein L48. It interacts with Oxa1L, a mitochondrial inner membrane protein that facilitates the insertion of both mitochondrial- and nuclear-encoded proteins from the mitochondrial matrix into the inner membrane [
].
Ribosomal RNA-processing protein 7 (RRP7) is an essential protein in yeast that is involved in pre-rRNA processing and ribosome assembly [
]. It is speculated to be required for correct assembly of rpS27 into the pre-ribosomal particle [,
].
This entry includes Ly6/PLAUR domain-containing protein 6 and Ly6/PLAUR domain-containing protein 6B (LYPD6/6B). They are prototoxins that belong to a larger family known as Ly-6/urokinase plasminogen activator receptor (Ly6/uPAR). They have 8-10 conserved cysteine residues that allow for the formation of disulfide bonds, constraining the protein to the 3-fingered motif secondary structure [
].Ly6/PLAUR domain-containing protein 6 (LYPD6) is a higher eukaryotic protein expressed in neurons. It modulates nicotinic acetylcholine receptors by selectively increasing Ca2+-influx through this ion channel [
]. LYPD6 carries an LU protein domain - about 80 amino acids long characterised by a conserved pattern of 10 cysteine residues []. It is a positive feedback regulator of Wnt/beta-catenin signalling, e.g. for patterning of the mesoderm and neuroectoderm in zebrafish gastrulation, where Lypd6 is GPI-anchored to the plasma-membrane and interacts with the Wnt receptor Frizzled8 and the co-receptor Lrp6 [].LYPD6B has been shown to modulate heteromeric alpha3beta4-containing nicotinic acetylcholine receptors [
].
EPIDERMAL PATTERNING FACTOR (EPF) is a family of plant epidermal cell growth factors. It is a signalling peptide that determines the spacing and separation of the development of stomatal cells in the upper epidermis of plant leaf cells [
,
].
Transition nuclear proteins (TNPs), major proteins found in the chromatin of condensing spermatids, have been implicated in spermatogenesis and male fertility [
]. This entry includes TNP3 and TNP4. Ram TNP3 and boar TP4 belong to the same group and probably play similar functions in chromatin remodelling during spermiogenesis []. TNP4 stimulates the DNA-relaxing activity of topoisomerase I []. This entry also includes human uncharacterized protein CXorf51.
TRAF3-interacting protein 1 (TRAF3IP1) recruits TRAF3 (tumour necrosis factor receptor-associated factor 3) and DISC1 (Disrupted-In-Schizophrenia 1) to the microtubules and is conserved from worms to humans [
]. The N-terminal region is the microtubule binding domain and is well-conserved; the C-terminal 100 residues, also well-conserved, constitute the coiled-coil region which binds to TRAF3. The central region of the protein is rich in lysine and glutamic acid and carries KKE motifs which may also be necessary for tubulin-binding, but this region is the least well-conserved []. In humans, it plays an inhibitory role on IL13 signaling by binding to IL13RA1. It is involved in suppression of IL13-induced STAT6 phosphorylation, transcriptional activity and DNA-binding [,
].This entry represents the N-terminal domain of TRAF3-interacting protein 1.
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 40S ribosomal protein SA from vertebrates (also known as laminin receptor 1), which is homologous to S2 of bacteria [
]. While the protein is found in the ribosome [,
], it is also a membrane receptor for laminin, growth factors, prion and pathogens [].
Protein EARLY FLOWERING 4 is a component of the central CCA1/LHY-TOC1 feedback loop in the circadian clock that promotes clock accuracy and is required for sustained rhythms in the absence of daily light/dark cycles [
,
].
This family of uncharacterized proteins from plants includes protein FERTILITY RESTORER RF2 (RF2) and protein YELLOW LEAF 1 (YL1) from Oryza sativa. RF2 is a mitochondrial glycine-rich protein that can restore fertility in rice varieties with LD-type cytoplasmic male sterility (CMS) [
]. YL1 is required for photosynthetic protein complex assembly in chloroplast thylakoid membranes during leaf development [].
MPB2C proteins are involved in regulating cell-to-cell trafficking of homeodomain proteins in plants. MPB2C negatively regulates KNOTTED1 (KN1) association to plasmodesmata and, consequently, KN1 cell-to-cell transport [
]. MPB2C has also been linked to roles in organization of cortical microtubules, stomata patterning, and tobamovirus infectivity [,
].
EIF1AD (also known as haponin) is a probable RNA-binding protein that plays a role in the cellular response to oxidative stress [
] and interacts with glyceraldehyde 3-phosphate dehydrogenase (GAPDH) []. EIF1AD contains an S1-like domain, and nuclear localization signals.
This entry includes prolyl-tRNA editing protein ProX from Acetoanaerobium sticklandii and uncharacterized eukaryotic proteins known as prolyl-tRNA synthetase associated domain-containing proteins. ProX functions in trans to edit the amino acid moiety from incorrectly charged Ala-tRNA(Pro) [
].
This entry includes protein SIEVE ELEMENT OCCLUSION (SEO) 1, 2 and 3 (or A, B and C) from Arabidopsis. They are phloem filament proteins required for filament formation [
].
This entry represents a group of proteins including CCDC159 and CCDC163. The function of CCDC159/163 is not clear. Homologues are predominantly from chordates.
The CLAVATA3/ESR-related (CLE) gene family has 31 CLE members in the Arabidopsis genome [
]. CLE sequences share a short conserved region of 14 amino acids [] and are thought to function in plant morphogenesis as intercellular signaling molecules [,
].This entry includes CLE27 and CLE43. CLE27 may have redundant roles with CLE16 and CLE17 in the Arabidopsis shoot apical meristem [
].
Zinc finger protein 469 (ZNF469) is found in chordates and is uncharacterised. Mutations in the ZNF469 gene are associated with brittle cornea syndrome, an autosomal-recessive disorder characterised by a thin cornea that tends to perforate, causing progressive visual loss and blindness [
]. The protein contains several C2H2-type zinc fingers.
PDZ domain-containing protein 8 (PDZD8) is a molecular tether, connecting endoplasmic reticulum (ER) and mitochondria membranes. This tethering is required for transfer of Ca
2+ions between the ER and mitochondrion, which is particularly important in neurones [
]. PDZD8 is a membrane protein containing a single transmembrane region and contains SMP-LTD (synaptotagmin-like mitochondrial-lipid binding protein) [] and PDZ domains and a phorbol-ester/DAG-type zinc finger. Homologues are found in metazoa.
While most bacteria synthesise lysine via diaminopimelate, a few species, such as Thermus thermophilus, and some hyperthermophilic archaea, synthesise this amino acid from alpha-aminoadipate (AAA). LysW plays an essential role in this pathway by preventing unstable intermediates from undergoing intramolecular cyclisation [
]. This is accomplished by covalent binding of the reactive amino group of AAA to a glutamate residue in LysW. The covalently attached AAA is subsequently converted to lysine and then released from LysW by the action of other proteins in this pathway.
Retrotransposon Gag-like protein 9 (RTL9) is a member of the neofunctionalized Ty3/gypsy retrotransposon family. They have lost essential structural features necessary for autonomous retrotransposition before divergence between mouse and human [
].
BTB/POZ domain-containing protein 18 (BTBD18) is a pachytene nuclear protein that regulates transcription activation through RNA polymerase II elongation at a subset of genomic piRNA loci [
].
Class II bacteriocins are small are ribosomally-synthesized, non-lantibiotic peptide antibiotics produced by many bacteria [
]. This entry represents a protein encoded within a number of operons responsible for class II bacteriocin production [,
,
]. It is generally the third protein in the operon and, together with the fourth protein, is responsible for transport to the extracellular environment [].
This entry describes an uncharacterised domain found broadly in proteins of surface carbohydrate biosynthesis regions. This family shows distant homology to regions of family
, of spore coat polysaccharide biosynthesis protein SpsB from Bacillus subtilis, etc.
Growth arrest-specific protein 8 (Gas8; also known as dynein regulatory complex subunit 4, DRC4) is a microtubule-binding protein localised to regions of dynein regulation in mammalian cells. In mouse, Gas8 is predominantly a testicular protein, whose expression is developmentally regulated during puberty and spermatogenesis. In humans, it is absent in infertile males who lack the ability to generate gametes. The localisation of Gas8 in the motility apparatus of post-meiotic gametocytes and mature spermatozoa, together with the detection of Gas8 also in cilia at the apical surfaces of epithelial cells lining the pulmonary bronchi and Fallopian tubes suggests that the Gas8 protein may have a role in the functioning of motile cellular appendages [
]. Homologues are also found in apicomplexans and invertebrates. In Chlamydomonas reinhardtii, Gas8 is a component of the nexin-dynein regulatory complex, which is a regulator of ciliary/flagellar motility [].
FIP-Fve (Fungal Immunomodulatory Protein Fve) is a major fruiting body protein from Flammulina velutipes, a mushroom possessing immunomodulatory activity [
]. It stimulates lymphocyte mitogenesis, suppresses systemic anaphylaxis reactions and oedema, enhances transcription of IL-2, IFN-gamma and TNF-alpha, and haemagglutinates red blood cells. It appears to be a lectin with specificity for complex cell-surface carbohydrates. Fve adopts a tertiary structure consisting of an immunoglobulin-like β-sandwich, with seven strands arranged in two beta sheets, in a Greek-key topology. It forms a non-covalently linked homodimer containing no Cys, His or Met residues; dimerisation occurs by 3-D domain swapping of the N-terminal helices and is stabilised predominantly by hydrophobic interactions [].
Microtubule-associated protein 10 (MAP10, also known as MTR120/KIAA1383) localises to stabilised MTs during interphase and to the mitotic apparatus during mitosis. It may promote microtubule stability and ensures normal progress of cytokinesis [
].
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 [
].
This entry represents LBH domain containing proteins, including protein LBH, LBHD1 and LBHD2.LBH (limb-bud and heart) protein may act as a transcriptional activator in mitogen-activated protein kinase signalling pathway to mediate cellular functions. It has been shown to regulate cardiac gene expression by modulating the combinatorial activities of key cardiac transcription factors, as well as their individual functions in cardiogenesis in mice [
].
Heat shock protein beta-9 (HspB9) is specifically expressed in testis, notably in the spermatogenic cells from late pachytene spermatocyte stage till elongate spermatid stage [
]. Its function is not clear.
This domain is found as the extreme C-terminal region of four extracellular protein (mostly protease) precursor sequences in Chthoniobacter flavus Ellin428,
In budding yeasts, Phosphatidylinositol transfer proteins (PITPs) are defined by their ability to transfer phosphatidylinositol (PtdIns) or phosphatidylcholine (PtdCho) monomers between membrane bilayers in vitro. The major PITP is encoded by SEC14. However, four other yeast SFH (Sec Fourteen Homologue) proteins designated Sfh2, Sfh3, Sfh4, and Sfh5, have been identified [
].This entry represents Sfh5 from fungi, a non-classical PITP. It has PtdIns transfer activity in vitro and may function in regulation of post-Golgi membrane trafficking events [
,
]. It is also involved in the organization of the actin cytoskeleton []. Sfh5 is a novel heme-binding protein with an unusual heme-binding arrangement that involves co-axial tyrosine/histidine coordination strategy and a complex electronic structure which penta-coordinates high spin Fe3. It is conserved across Fungi and may play a role organic oxidant-induced stress responses, being the founding member of a new class of hemoproteins [].
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, slime mould, fungal and mammalian L7 ribosomal proteinsThis model describes archaeal 50S ribosomal protein L30. These proteins share similarity to the longer eukaryotic 60S ribosomal protein L7 and to the much shorter (~60 residue) bacterial 50S ribosomal protein L30.
This family includes zinc metalloprotein McbB, part of the maturase system for microcin B17, a thiazole/oxazole-modified microcin (TOMM). Other members of this family belong to very different gene neighbourhoods. The Cys residues that act as zinc ligands are conserved in most members, but for rare members are jointly absent [
].
Members of this family occur only in the genus Leptospira, always encoded between genes for the YajC and SecD components of the Sec preprotein translocase. Sequences have an N-terminal signal peptide and a C-terminal transmembrane segment. Between these are regions of non-globular, low-complexity sequence including Lys-rich and Ser/Thr/Asn/Glu-rich regions.
A number of bacterial and plant toxins act by inhibiting protein synthesis in eukaryotic cells. The toxins of the shiga and ricin family inactivate 60S ribosomal subunits by an N-glycosidic cleavage which releases a specific adenine base from the sugar-phosphate backbone of 28S rRNA [
,
,
]. Members of the family include shiga and shiga-like toxins, and type I (e.g. trichosanthin and luffin) and type II (e.g. ricin, agglutinin and abrin) ribosome inactivating proteins (RIPs). All these toxins are structurally related. RIPs have been of considerable interest because of their potential use, conjugated with monoclonal antibodies, as immunotoxins to treat cancers. Further, trichosanthin has been shown to have potent activity against HIV-1-infected T cells and macrophages []. Elucidation of the structure-function relationships of RIPs has therefore become a major research effort. It is now known that RIPs are structurally related. A conserved glutamic residue has been implicated in the catalytic mechanism []; this lies near a conserved arginine, which also plays a role in catalysis [].This entry represents type I and type II RIPs. It does not include shiga and shiga-like toxins.
Putative immunoglobulin-blocking virulence protein
Type:
Family
Description:
Members of this family are putative virulence proteins of Mycoplasma and Ureaplasma species. They share a region of sequence similarity (see
) with protein M, a Mycoplasma genitalium protein that binds a conserved light chain region of IgG and blocks its protective function of antigen-specific binding. Proteins in this entry contains an N-terminal signal-anchor domain and a proline-rich linker domain, and a C-terminal extension, in addition to the protein M-like domain recognised by
.
A number of bacterial and plant toxins act by inhibiting protein synthesis in eukaryotic cells. The toxins of the shiga and ricin family inactivate 60S ribosomal subunits by an N-glycosidic cleavage which releases a specific adenine base from the sugar-phosphate backbone of 28S rRNA [
,
,
]. Members of the family include shiga and shiga-like toxins, and type I (e.g. trichosanthin and luffin) and type II (e.g. ricin, agglutinin and abrin) ribosome inactivating proteins (RIPs). All these toxins are structurally related. RIPs have been of considerable interest because of their potential use, conjugated with monoclonal antibodies, as immunotoxins to treat cancers. Further, trichosanthin has been shown to have potent activity against HIV-1-infected T cells and macrophages []. Elucidation of the structure-function relationships of RIPs has therefore become a major research effort. It is now known that RIPs are structurally related. A conserved glutamic residue has been implicated in the catalytic mechanism []; this lies near a conserved arginine, which also plays a role in catalysis [].This entry represents a conserved site of the Ribosome-inactivating protein conserved site
Proteins in this family contain a highly conserved tripeptide motif LYR close to the N terminus. Human LYR motif-containing protein 1 (LYRM1) is highly expressed in omental adipose tissue of obese subjects, promotes preadipocyte proliferation, and inhibits apoptosis of preadipocytes [
].
Arabinogalactan-proteins (AGPs) are cell wall proteoglycans and are widely distributed in the plant kingdom. They have a predicted glycosylphosphatidylinositol lipid anchor and are suggested to be involved in cell-cell signaling [
]. This entry includes AGP25 and AGP26 from Arabidopsis.
Metallo-beta-lactamase domain-containing protein 1
Type:
Family
Description:
This family includes metallo-beta-lactamase domain-containing protein 1 (MBLAC1), an endoribonuclease that catalyses the hydrolysis of histone-coding pre-mRNA 3'-end. It is involved in histone pre-mRNA processing during the S-phase of the cell cycle, which is required for entering/progressing through S-phase[
].
Proteins in this entry contain WD40 repeats. Besides a number of uncharacterized proteins, the family includes the following:
WD repeat-containing protein 44 (WDR44; also known as Rabphilin-11), found in vertebrates, which binds the small G protein Rab11 and is implicated in vesicle recycling [
].2-deoxy-glucose resistant protein 2 (Dgr2) from yeast, which increases cellular tolerance to 2-deoxy-glucose [
].
This entry represents a group of plant proteins, including SCD2 from Arabidopsis. SCD2 (STOMATAL CYTOKINESIS DEFECTIVE 2) functions in clathrin-mediated membrane transport. In Arabidopsis, loss of SCD2 function disrupts cytokinesis and cell expansion and impairs fertility [
].
Sushi domain-containing protein 4 (SUSD4) contains several Sushi or complement control protein domains [
]. It functions as a complement inhibitor and a tumour suppressor [].
This entry contains proteins with a BING4-like, C-terminal domain. WD repeat-containing protein 46 (WDR46) is a component of the nuclear scaffold, which is an insoluble structure that contributes to the inner nuclear organization. WDR46 is a fundamental scaffold component of the nucleolar structure, binding nucleolin and DDX21 [
]. Also in this family is U3 small nucleolar RNA-associated protein 7 (UTP7) from baker's yeast, which is involved in nucleolar processing of pre-18S ribosomal RNA [].
This entry represents a group of animal proteins, including CCDC3 from humans. CCDC3 is a secretory protein that represses tumour necrosis factor-alpha/nuclear factor kappaB-induced endothelial inflammation [
].
Peridinin-chlorophyll-protein, a water-soluble light-harvesting complex that has a blue-green absorbing carotenoid as its main pigment, is present in most photosynthetic dinoflagellates. These proteins are composed of two similar repeated domains. These domains constitute a scaffold with pseudo-twofold symmetry surrounding a hydrophobic cavity filled by two lipid, eight peridinin, and two chlorophyll a molecules [
].
RING finger protein 207 (RNF207) is a regulator of cardiac excitation probably by effects on HERG trafficking and localization in a heat shock protein-dependent manner [
]. RNF207 contains a RING-type ring finger and an atypical B box-type ring finger.
Following the action of a flavin-dependent L-amino acid oxidase that converts L-tryptophan to indole-3-pyruvate imine, the enzymes VioB (this family; also known as 2-imino-3-(indol-3-yl)propanoate dimerase,
), RebD, and StaD can ligate two molecules, forming a coupled iminophenyl-pyruvate dimer. In the violacein biosynthesis pathway, this compound is acted on by VioE before it cyclizes spontaneously to chromopyrrolic acid. In the pathways of homologue StaD (staurosporine), chromopyrrolate is formed, and the enzyme is referred to as chromopyrrolate synthase. RebD is very similar to StaD, but acts on chlorinated Trp-derived molecules [
].
This entry represents a group of plant proteins, including protein EARLY FLOWERING 3 (ELF3) from Arabidopsis and Hd17 from rice. It may function as a modulator of light signal transduction downstream of phytochromes [
]. Hd17 (also known as OsELF3) is involved in rice photoperiodic flowering [].
Packaging protein 1 (also known as IVa2) is a component of the packaging machinery which encapsidates the viral DNA into preformed capsids and transcriptional activator of the viral major late promoter (MLP) [
]. It binds, along with packaging proteins 2 and 3, to the specific packaging sequence on the left end of viral genomic DNA and displays ATPase activity thereby providing the power stroke of the packaging machinery [,
].
This entry represents a group of plant proteins, including protein HEAT INTOLERANT 4 (HIT4) from Arabidopsis. HIT4 is a chromocentre-localized protein involved in heat-triggered reorganization of chromatin and release of transcriptional gene silencing [
,
].
This entry includes CP12, a chloroplast protein that regulates the Calvin cycle responsible for CO2 assimilation [
]. Oxidized CP12 forms a supramolecular complex with two key Calvin cycle enzymes, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and PRK (phosphoribulokinase), down-regulating their activity. It also interacts with other enzymes such as aldolase and malate dehydrogenase []. This entry also includes proteins from Cyanobacteria (blue-green algae).
Arabidopsis TIME FOR COFFEE (TIC) is a circadian regulator that coordinates developmental, metabolic, and environmental signals [
,
]. It controls root meristem size by changes in auxin accumulation [].
This entry represents a group of plant proteins, including CLAVATA3/ESR (CLE)-related protein 25/26 (CLE25/26) from Arabidopsis. They are extracellular signal peptides involved in cell-to-cell communication in concert with different receptors in a range of processes during plant development [
,
].
Proteins in this entry contain WD40 repeats, and include WD repeat-containing proteins 19 (WDR19), from mammals, and dyf-2 from nematodes. Both WDR19 and dyf-2 are components of the IFT complex A (IFT-A), which is required for retrograde ciliary transport [
,
]. Mutations in the WDR19 gene are associated with numerous diseases, including cranioectodermal dysplasia 4, short-rib thoracic dysplasia 5 with or without polydactyly, nephronophthisis 13 [], and Senior-Loken syndrome 8 [].
This entry includes coiled-coil domain-containing proteins 74A (CCDC74A), 74B (CCDC74B) and 92 (CCDC92).Coiled-coil domain-containing protein 92 (CCDC92) is an interferon-stimulated protein that plays a role in innate immunity. It strongly inhibits ebolavirus transcription and replication through the formation of a complex with viral RNA-bound nucleocapsid (NP) that prevents the transport of NP to the cell surface [
]. It has also been shown to interact with centrosomal protein CEP164 [], which is required for primary (nonmotile) cilium formation [].
Proteins in this family are mostly from animals. The only characterized protein is LisH domain-containing protein ARMC9, which is localized to the basal body of a cilium and is upregulated during ciliogenesis. Mutations in the ARMC9 gene cause Joubert Syndrome, a recessive neurodevelopmental disorder characterized by hypotonia, ataxia, abnormal eye movements, and variable cognitive impairment [
].
This entry includes tetratricopeptide repeat proteins 21A (TTC21A) and 21B (TTC21B), and other homologues with numerous tetratricopeptide repeats. TTC21B is a component of the IFT complex A (IFT-A), which is required for retrograde ciliary transport. Intraflagellar transport (IFT) is required for cilium assembly and trafficking within cilia [
]. Several diseases results from mutations in the TTC21B gene including nephronophthisis 12, short-rib thoracic dysplasia 4 with or without polydactyly, and Joubert syndrome 11 [].
This entry includes EF-hand domain-containing protein D1/2 (EFHD1/2). EFHD1 may function as a mitochondrial Ca(2+) sensor underlying Ca(2+)-dependent activation of mitoflashes [
]. EFHD2 is a Ca2+ binding adapter protein involved in various cellular functions []. In mice, EFHD2 (also known as Swiprosin-1) may regulate B-cell receptor (BCR)-induced immature and primary B-cell apoptosis [].
Autophagy-related (Atg) proteins play a role in autophagy. Atg29 forms a complex with Atg17 and Atg31. When autophagy is initiated, the Atg17-Atg31-Atg29 complex is first targeted to the phagophore assembly site (PAS) and then recruits other Atg proteins [
]. The complex is recruited to the PAS by Atg11. Atg29 contains an N-terminal functional domain, whereas the C terminus plays a regulatory role. Phosphorylation of the C-terminal domain of Atg29 is required for its interaction with Atg11 and proper PAS localization [].The tertiary structure of Atg29 (within the Atg17-Atg29-Atg31 subcomplex) has been determined in part, showing a central three-helix bundle [
].
ZNF750 is a transcription factor that controls epithelial homeostasis by inhibiting progenitor genes while inducing differentiation genes [
]. ZNF750 and related proteins contain a zinc finger domain. Human proline-rich protein 35 is related, but its function is not clear.
This serine and alanine-rich surface protein repeat, about 175 amino acids long, occurs up to nine times in surface proteins of some Lactobacillus strains. Members proteins have the N-terminal variant signal sequence described by
and C-terminal LPXTG signals for surface attachment by sortase.
Parathyroid hormone/parathyroid hormone-related protein
Type:
Family
Description:
Parathyroid hormone (PTH) is a polypeptidic hormone that elevates calcium level by dissolving the salts in bone and preventing their renal excretion. Parathyroid hormone-related protein (PTH-rP) is structurally related to PTH [
] and seems to play a physiological role in lactation, possibly as a hormone for the mobilisation and/or transfer of calcium to the milk. It also regulates chondrocytic differentiation and endochondral bone formation [].PTH and PTH-rP bind to the same G-protein coupled receptor.This entry represents parathyroid hormone and parathyroid hormone-related protein.
Mitochondrial escape protein 2 (also known as RNA12) plays a role in maintaining the mitochondrial genome and in controlling mtDNA escape [
,
]. It is also involved in the regulation of mtDNA nucleotide structure and number []. Additionally, this protein have a dispensable role in the early maturation of pre-rRNA [].
PIANP modulates gamma-secretase-mediated cleavage of E-Cadherin and therefore can affect junctional integrity and function [
]. It has been shown to interact in vitro with the immune inhibitory receptor PILR-alpha, and may be involved in immune regulation [].
Helicobacter pylori is a causative agent of gastritis and peptic ulceration in humans. As the first step towards development of a vaccine against H. pylori infection, many attempts have been made to identify protective antigens. Potential targets for vaccine development are H. pylori-specific proteins that are surface-exposed and highly antigenic.This family consists of putative outer membrane proteins, mainly from H. pylori.
This entry represents a group of plant proteins, including BG1 (BIG GRAIN 1) and BIG1L from rice and BG1A-E from Arabidopsis. BG1 over-expressing plants exhibit increased grain size with both bigger length and width. BG1 functions in auxin pathway and positively regulates biomass, grain size and yield in rice [
,
].
Methyl-CpG-binding domain-containing protein 10/11
Type:
Family
Description:
This entry represents a group of methyl-CpG-binding domain-containing proteins from plants, including MBD10/11 from Arabidopsis.Cytosine methylation at symmetrical CpG and CpNpG sequences plays a key role in the epigenetic control of plant growth and development. In animals, the methylation signal is recognized by methyl-CpG-binding domain (MBD) proteins that specifically bind methylated CpG dinucleotides. In Arabidopsis thaliana 12 putative MBD proteins have been identified. However, the presence of an MBD motif does not necessarily point to methyl-CpG-binding activity. The Arabidopsis proteins AtMBD5, AtMBD6 and AtMBD7 have been proven to bind methyl CpG in vitro and to localize to highly methylated chromocentres in vivo, but none of the other Arabidopsis MBD-containing proteins show these properties, and therefore seem to be non-functional MBDs [
,
].
This entry includes CLAVATA3/ESR (CLE)-related protein 9-13 (CLE9-13) from Arabidopsis and FON2 SPARE1 (FOS1) form from rice. FOS1, a CLE-related protein, regulates floral meristem maintenance [
].The CLE proteins share a C-terminal CLE domain with CLV3, a small secreted polypeptide that is active as a ligand and has a function in shoot apical meristem maintenance [
]. In general, the CLE-related proteins are C-terminally processed to generate an active CLE peptide []. These small secreted peptide hormones then function in a variety of developmental and physiological processes [,
]. CLV3 and other A-type CLE peptides are involved in the suppression of stem cell development in root and shoot development, in contrast to the B-type CLE peptides, CLE41 and CLE44, in the case of Arabidopsis, which are not [].
This entry includes CLAVATA3/ESR (CLE)-related proteins 1-4 (CLE1/3/4) from Arabidopsis and CLE33 from Medicago truncatula. CLE33 is a signaling peptide involved in the regulation of root colonization by arbuscular mycorrhizal (AM) fungi. It moves from root to shoot to function with the receptor kinase SUNN, in a signaling pathway that repress strigolactone biosynthetic genes and strigolactone content in the roots, and consequently reduces the promotion of further colonization by AM fungi [
].The CLE proteins share a C-terminal CLE domain with CLV3, a small secreted polypeptide that is active as a ligand and has a function in shoot apical meristem maintenance [
]. In general, the CLE-related proteins are C-terminally processed to generate an active CLE peptide []. These small secreted peptide hormones then function in a variety of developmental and physiological processes [,
]. CLV3 and other A-type CLE peptides are involved in the suppression of stem cell development in root and shoot development, in contrast to the B-type CLE peptides, CLE41 and CLE44, in the case of Arabidopsis, which are not [].
Upon vascular injury, flowing blood is exposed to cells expressing tissue factor (TF) on their surfaces and FVII/FVIIa binds to its receptor/cofactor TF and is rapidly activated to FVIIa and the activity of bound FVIIa is dramatically enhanced. The TF/FVIIa complex activates zymogens factor X (FX) and factor IX (FIX). The FXa, in the absence of activated cofactor factor Va (FVa) generates only trace amounts of thrombin. Although insufficient to initiate fibrin polymerisation alone, these small amounts of thrombin, however, back activate factors V (FV), VIII (FVIII), and XI (FXI). FVIII and FV function as membrane-bound cofactors for proteinases FIXa and FXa, respectively increasing the Vmax of the reaction complexes dramatically. Amplification of the pro-coagulant response consequently occurs through formation of the tenase complex FIXa/FVIIIa and the thrombinase complex FXa/FVa that generate sufficient amounts of thrombin to mediate sustained haemostasis.In addition to its function in cleaving soluble fibrinogen to form insoluble fibrin monomers, thrombin can also activate an anticoagulant pathway. Thrombomodulin (TM), a receptor present on the endothelial cell surface, binds thrombin and alters thrombin's substrate specificity through an allosteric mechanism. Bound to TM, thrombin can no longer efficiently proteolyse its pro-coagulant substrates FV, FVIII and fibrinogen. The thrombin-TM complex proteolytically activates its substrate protein C (PC) to activated protein C (APC). In complex with its cofactor protein S (PS), APC rapidly inactivates pro-coagulant factors FVa and FVIIIa by further proteolysis in a negative feedback loop. Activation of protein C by thrombin bound to thrombomodulin is enhanced by endothelial protein C receptor (EPCR). The EPCR is an N-glycosylated type I membrane protein and mutations in this EPCR gene have been associated with venous thromboembolism and myocardial infarction, as well as with late foetal loss during pregnancy.
This entry includes a group of VQ motif-containing proteins from plants, including VQ29 from Arabidopsis.In general, Arabidopsis VQPs interacted specifically with the C-terminal WRKY domains of group I and the sole WRKY domains of group IIc WRKY transcription factors [
,
]. Arabidopsis VQPs reported to control stress responses include the calmodulin (CaM)-binding protein CamBP25 and VQ9, which regulate osmotic and salinity tolerance, respectively, the sigma factor binding proteins SIB1 and SIB2, which act as activators of WRKY33 in plant defence, and the negative regulator of the jasmonate defence pathway [].
This entry includes a group of VQ motif-containing proteins (VQPs) from plants, including VQ4/11/13/19/31/33 from Arabidopsis. This subgroup of VQPs can be phosphorylated by the MAPKs MPK3 and MPK6, and have been named MPK3/6-targeted VQPs (MVQs). VQ4, also known as MVQ1, may act as an inhibitor of WRKY functions [
].In general, Arabidopsis VQPs interacted specifically with the C-terminal WRKY domains of group I and the sole WRKY domains of group IIc WRKY transcription factors [
,
]. Arabidopsis VQPs reported to control stress responses include the calmodulin (CaM)-binding protein CamBP25 and VQ9, which regulate osmotic and salinity tolerance, respectively, the sigma factor binding proteins SIB1 and SIB2, which act as activators of WRKY33 in plant defence, and the negative regulator of the jasmonate defence pathway [].
This entry represents a group of plant proteins, including protein PHYTOCHROME KINASE SUBSTRATES 1-4 (PKS1-4) from Arabidopsis. PKS1 is a novel phot1 signaling element during phototropism, while PKS2 is a phototropin signaling element that regulates leaf flattening and leaf positioning [
]. PKS4 modulates phytochrome-mediated control of hypocotyl growth orientation [].
This entry includes a group of VQ motif-containing proteins from plants, including MKS1 (VQ21, At3g18690) and VQ8/17/18/20/25 from Arabidopsis.In general, Arabidopsis VQPs interacted specifically with the C-terminal WRKY domains of group I and the sole WRKY domains of group IIc WRKY transcription factors [
,
]. Arabidopsis VQPs reported to control stress responses include the calmodulin (CaM)-binding protein CamBP25 and VQ9, which regulate osmotic and salinity tolerance, respectively, the sigma factor binding proteins SIB1 and SIB2, which act as activators of WRKY33 in plant defence, and the negative regulator of the jasmonate defence pathway [].
This entry includes a group of VQ motif-containing proteins from plants, including VQ1/10 from Arabidopsis.In general, Arabidopsis VQPs interacted specifically with the C-terminal WRKY domains of group I and the sole WRKY domains of group IIc WRKY transcription factors [
,
]. Arabidopsis VQPs reported to control stress responses include the calmodulin (CaM)-binding protein CamBP25 and VQ9, which regulate osmotic and salinity tolerance, respectively, the sigma factor binding proteins SIB1 and SIB2, which act as activators of WRKY33 in plant defence, and the negative regulator of the jasmonate defence pathway [].
This entry includes AT-hook motif nuclear-localized protein 1-14 (AHL1-14) from Arabidopsis. They have two conserved structural units, the AT-hook motif and the Plant and Prokaryote Conserved (PPC) domain, the latter also known as DUF296. Members of the AHL family regulate diverse aspects of growth and development in plants [
]. AHL1 is a transcription factor that specifically binds AT-rich DNA sequences related to the nuclear matrix attachment regions (MARs) [].
This entry includes a group of VQ motif-containing proteins from plants, including VQ15/22 from Arabidopsis. VQ15, also known as calmodulin-binding protein 25, can work as a negative regulator of osmotic stress tolerance [].In general, Arabidopsis VQPs interacted specifically with the C-terminal WRKY domains of group I and the sole WRKY domains of group IIc WRKY transcription factors [
,
]. Arabidopsis VQPs reported to control stress responses include the calmodulin (CaM)-binding protein CamBP25 and VQ9, which regulate osmotic and salinity tolerance, respectively, the sigma factor binding proteins SIB1 and SIB2, which act as activators of WRKY33 in plant defence, and the negative regulator of the jasmonate defence pathway [].
Members of this protein family belong to the same domain family as AMMECR1
, a mammalian protein whose deficit is involved in the association of Alport syndrome, midface hypoplasia, intellectual disability and elliptocytosis in humans [
]. Members of the present family occur as part of a three gene system with a homologue of the mammalian protein Memo (Mediator of ErbB2-driven cell MOtility), and an uncharacterised radical SAM enzyme [].
This entry includes Bfr1 and related proteins, including C458.02c from the fission yeast Schizosaccharomyces pombe. Bfr1 is implicated in secretion and nuclear segregation in Saccharomyces cerevisiae [
].
Rxt2 is a component of the Rpd3 histone deacetylase complex (HDAC). Histone deacetylation plays an important role in transcriptional regulation, cell cycle progression and developmental events [
].
Rotavirus non-structural protein 2 (NSP2) is a basic protein which possesses RNA-binding activity and is essential for genome replication [
]. It may also be important for viral RNA packaging.
This entry represents the Microviridae F protein superfamily, including capsid protein F and capsid protein VP1. Capsid protein F is the major capsid component in single-stranded DNA bacteriophages. 60 copies of this protein are present in the virion [
].
HMG box-containing protein 1 (HBP1) is a high mobility group (HMG) box transcription factor that negatively regulates the Wnt-beta-catenin pathway [
] and is involved in histone H1(0) gene expression []. It binds the transcription factor TCF4 and prevents it from binding to its target genes, including c-MYC and CYCLIN D []. It acts as a tumour suppressor and an important effector in oncogene-induced premature senescence [].
Multidrug resistance proteins are molecular pumps that participate in a low energy shock adaptive response in some bacteria. The MdtABC tripartite complex is composed of MdtA, MdtB and MdtC, and confers resistance against novobiocin and deoxycholate [
]. The mdtABC operon is transcriptionally activated by BaeR and belongs to the AcrB/AcrD/AcrF familyThis entry represents MdtC which forms a heteromultimer with MdtB.
This family of bacterial proteins includes the transcriptional regulatory proteins senN and senS, which regulate the expression of extracellular-protein genes of Bacillus subtilis [
,
].
