Alpha-tubulin N-acetyltransferase was originally known as mechanosensory abnormality protein 17 (Mec-17), as it is the protein product of one of the 18 genes required for the development and function of the touch receptor neuron for gentle touch []. Mec-17 specifically acetylates 'Lys-40' in alpha-tubulin on the lumenal side of microtubules []. It is inefficient, and its activity is enhanced when tubulin is incorporated in microtubules []. It may affect microtubule stability and regulate microtubule dynamics. It can function as an enzymatic timer for microtubule lifetimes [].
Members of this family have a conserved nucleotide-binding motif GXXGXGKT and a nucleotide-binding fold. Member protein YjeE of Haemophilus influenzae (HI0065) was shown to have ATPase activity [, ]. The protein has a nucleotide-binding fold with a four-stranded parallel β-sheet flanked by antiparallel β-strands on each side. The topology of the β-sheet is unique among P-loop proteins and has features of different families of enzymes. ADP has been shown to bind to the P-loop in the presence of Mg2+.Recently YjeE has been renamed as TsaE []. It is responsible for tRNA threonylcarbamoyl adenosine modification together with proteins TsaB, TsaC, and TsaD, and probably forms a complex with them [, ].
This entry represents the UPF0234 family of uncharacterised proteins, which includes YajQ.In Pseudomonas syringae, YajQ functions as a host protein involved in the temporal control of bacteriophage Phi6 gene transcription. It has been shown to bind to the phage's major structural core protein P1, most likely activating transcription by acting indirectly on the RNA polymerase. YajQ may remain bound to the phage particles throughout the infection period [, ]. Earlier, YajQ was characterized as a putative nucleic acid-binding protein based on the similarity of its (ferredoxin-like) three-dimensional topology with that of RNP-like RNA-binding domains [, ].
C2CD5, also known as CDP138 or KIAA0528, is a C2 domain-containing phosphoprotein. It is a substrate for protein kinase Akt2, and it may be involved in the regulation of GLUT4 vesicle-plasma membrane fusion in response to insulin. The C2 domain of C2CD5 was shown to be capable of binding Ca(2+) and lipid membranes []. Other studies indicate that C2CD5 is a CDK5- and FIBP-interacting protein, forming a complex with these proteins that is involved in cell proliferation and migration [].This entry represents the C2 domain of C2CD5.
Takeout (To) proteins are found in insects and have important roles in various aspects of their physiology and behavior. To was discovered in Drosophila melanogaster as a clock-regulated gene, acting as a molecular link between circadian rhythms and feeding behavior [, ]. In addition, To is secreted in the hemolymph of adult males and affects male courtship behavior []. To proteins have an unusual α/β-wrap fold, the so-called TULIP fold [], seen also in juvenile hormone-binding proteins (JHBPs), with which they share limited sequence similarity. This fold is thought to constitute a scaffold for the binding and/or transport of hydrophobic ligands [, ].
F420 (or 8-hydroxy-5-deazaflavin) is a coenzyme involved in redox reactions in methanogens. A Genome Properties metabolic reconstruction for F420 biosynthesis shows that slightly over 10 percent of all prokaryotes with fully sequenced genomes, including about two thirds of the Actinomycetales, make F420. This subfamily within the PPOX family occurs in at least 19 distinct species of F420 producers and is likely to bind F420 rather than FMN (flavin mononucleotide or riboflavin-5'-phosphate). The member OxyR was shown in Streptomyces rimosusto use F420 to catalyze a C5a-C11a reduction in tetracycline or oxytetracycline biosynthesis [, ], and OxyR is also known as 5a,11a-dehydrotetracycline/5a,11a-dehydrooxytetracycline reductase.
Wnt morphogens control embryonic development and homeostasis in adult tissues. In vertebrates the N-terminal WIF domain (WIF-1WD) of Wnt inhibitory factor 1 (WIF-1) binds Wnt ligands.This entry represents the WIF domain, it is found in the RYK tyrosine kinase receptors and WIF the Wnt-inhibitory-factor. The domain is extracellular and contains two conserved cysteines that may form a disulphide bridge. This domain is Wnt binding in WIF, and it has been suggested that RYK may also bind to Wnt []. The WIF domain of WIF-1 was suggested to have a function in inhibiting Wnt signalling [].
Intracellular chloride ion channel proteins (CLICs) has been shown to exist in both soluble and integral membrane forms. The CLIC family consists of six human members, and is a subgroup of the glutathione-S-transferase (GSTs) superfamily. Chloride intracellular channel protein 3 (CLIC3) was identified as a potential binding partner of a mitogen-activated protein kinase, suggesting that it may participate in cellular growth control [], but its role to date is unclear. The soluble form of CLIC3 possesses a GST-like form with a more open and polar active site than that of other CLIC proteins [].
ZMYND11 (also known as BS69) was identified as a nuclear protein that specifically binds adenoviral E1A and Epstein-Barr viral EBNA2 proteins, suppressing their transactivation functions []. ZMYND11 is a multi-domain protein, containing bromo, PHD, PWWP, and MYND domains. The tandem Bromo-PWWP domains of ZMYND11 specifically recognise histone H3.3 trimethylated at lysine 36 (H3.3K36me3), thereby linking ZMYND11 to transcriptional elongation, tumour suppression and pre-mRNA splicing [, ].This PWWP domain is also found in ZMYND8. ZMYND8 recognizes dual histone modification mark H3K4me1-H3K14ac, and can function to counteract gene expression [, ]. Both ZMYND11 and ZMYND8 function in chromatin remodelling, consistent with other PWWP-containing proteins [].
G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups []. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence []. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [, , , , ]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice []. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [].The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [, , ].Several 7TM receptors have been cloned but their endogenous ligands areunknown; these have been termed orphan receptors. GPR37 was isolated from aset of human brain frontal lobe expressed sequence tags. The GPR37 genomicsequence was subsequently mapped to chromosome 7. A putative orthologue, 83%identical to the human form in terms of predicted amino acid sequence, hassince been identified in the mouse genome and mapped to chromosome 6. Northern blot analyses revealed a highly expressed 3.8kb mRNA and a less abundant 8kb mRNA in both human and mouse brain. The 3.8kb mRNA was also less abundantly expressed in human liver and placenta, and a further 3kb mRNA was found in mouse testis [].
This entry represents the RNA recognition motif (RRM) of SR140 (also known as U2SURP) which is a putative splicing factor mainly found in higher eukaryotes. Although it was initially identified as one of the 17S U2 snRNP-associated proteins, the molecular and physiological function of SR140 remains unclear []. SR140 contains an N-terminal RNA recognition motif (RRM), a SWAP/SURP domain that is found in a number of pre-mRNA splicing factors in the middle region, and a C-terminal arginine/serine-rich domain (RS domain).Proteins containing this domain also include Arabidopsis RRC1, which is a splicing factor which is required for phytochrome B (phyB) signal transduction [].
This family consists of the DegQ (formerly sacQ) regulatory peptides. The DegQ family of peptides control the rates of synthesis of a class of both secreted and intracellular degradative enzymes in Bacillus subtilis. DegQ is 46 amino acids long and activates the synthesis of degradative enzymes. The expression of this peptide was shown to be subjected both to catabolite repression and DegS-DegU-mediated control. Thus allowing an increase in the rate of synthesis of degQ under conditions of nitrogen starvation []. DegQ also affects protease and levansucrose production [].
This family consists of the DVL family of proteins. In a gain-of-function genetic screen for genes that influence fruit development in Arabidopsis, DEVIL (DVL) gene was identified. DVL (also known as Small polypeptide ROTUNDIFOLIA) is a small protein and over expression of the protein results in pleiotropic phenotypes featured by shortened stature, rounder rosette leaves, clustered inflorescences, shortened pedicles, and siliques with pronged tips. DVL family is a novel class of small polypeptides and the overexpression phenotypes suggest that these polypeptides may have a role in plant development playing a role as negative regulators of cell proliferation [, , ].
This entry includes coiled-coil domain-containing proteins 90 (CCDC90) and related proteins. CCDC90A is a key regulator of the mitochondrial calcium uniporter (MCU) and hence was renamed MCUR1 [, , ]. A study in mammals and in yeast homologue fmp32 has reported that MCUR1 is a cytochrome c oxidase assembly factor and that it has an indirect role as a regulator of MCU [], however, subsequent publications confirmed the function of MCUR1 as a regulator of MCU [, ]. The role of CCDC90B proteins is still not known.
This domain is found at the N-terminal of adhesins and hypothetical adhesin-like proteins from Mycoplasma pneumoniae and Mycoplasma genitalium, including adhesin P1 which was first identified as the major determinant for cytoadherence and gliding motility in M. pneumoniae [, ]. P1 forms a transmembrane adhesion complex with P40/P90, called 'Nap', which mediates motility and infectivity in these organisms. It consists of a large N-terminal domain that adopts a β-propeller topology and a smaller, more conserved C-terminal domain followed by a transmembrane domain. The C-terminal domain acts as a stalk connecting the large N-terminal domain with the outer surface of the cell membranes [, ].
The annexins (or lipocortins) are a family of proteins that bind to phospholipids in a calcium-dependent manner []. The 12 annexins common to vertebrates are classified in the annexin A family and named as annexins A1-A13 (or ANXA1-ANXA13), leaving A12 unassigned in the official nomenclature. Annexins outside vertebrates are classified into families B (in invertebrates), C (in fungi and some groups of unicellular eukaryotes), D (in plants), and E (in protists) []. Annexins are absent from yeasts and prokaryotes [].Most eukaryotic species have 1-20 annexin (ANX) genes. All annexins share a core domain made up of four similar repeats, each approximately 70 amino acids long []. Each individual annexin repeat (sometimes referred to as endonexin folds) is folded into five α-helices, and in turn are wound into a right-handed super-helix; they usually contain a characteristic 'type 2' motif for binding calcium ions with the sequence 'GxGT-[38 residues]-D/E'. Animal and fungal annexins also have variable amino-terminal domains. The core domains of most vertebrate annexins have been analysed by X-ray crystallography, revealing conservation of their secondary and tertiary structures despite only 45-55% amino-acid identity among individual members. The four repeats pack into a structure that resembles a flattened disc, with a slightly convex surface on which the Ca2+ -binding loops are located and a concave surface at which the amino and carboxyl termini come into close apposition.Annexins are traditionally thought of as calcium-dependent phospholipid-binding proteins, but recent work suggests a more complex set of functions. The family has been linked with inhibition of phospholipase activity, exocytosis and endocytosis, signal transduction, organisation of the extracellular matrix, resistance to reactive oxygen species and DNA replication [].This entry represents Human annexin type VIII, it was first identified in 1989 []; the 327 amino acidprotein was designated vascular anticoagulant (VAC) beta. It was found to beexpressed in placenta, lung endothelia, skin, liver and kidney. It sharesfour internal repeats with other annexin family members, but its 5' codingDNA sequence and untranslated region are unique []. The type VIII gene was found to be selectively over-expressed in acute promyelocytic leukaemia, anddifferentially expressed by chondrocytes, suggesting a putative link with longitudinal growth of the vertebrate skeleton [].
The baculovirus, Autographa californica nuclear polyhedrosis virus (AcMNPV), telokin-like protein (Tlp20) lies in a region of the baculoviral genome that is expressed late in the viral replication cycle, however its function is unknown. Tlp20 was discovered using anti-telokin antibodies, telokin being the C-terminal domain of smooth-muscle myosin light-chain kinase []. Both Tlp20 and telokin display a seven-stranded antiparallel β-barrel structure, although the 3-dimensional structures of the β-barrels are different and there is no sequence homology between the two. Tlp20 is structurally similar to dUTPase in its fold and trimeric assembly [].
The baculovirus, Autographa californica nuclear polyhedrosis virus (AcMNPV), telokin-like protein (Tlp20) lies in a region of the baculoviral genome that is expressed late in the viral replication cycle, however its function is unknown. Tlp20 was discovered using anti-telokin antibodies, telokin being the C-terminal domain of smooth-muscle myosin light-chain kinase []. Both Tlp20 and telokin display a seven-stranded antiparallel β-barrel structure, although the 3-dimensional structures of the β-barrels are different and there is no sequence homology between the two. Tlp20 is structurally similar to dUTPase in its fold and trimeric assembly [].
The Influenza A virus belongs to the class of ssRNA negative-strand viruses. Influenza virus NS2 protein (also known as NEP) has an important role in the nucleocytoplasmic transport of the viral ribonucleoprotein. The NS2 proteins perform this function in virus-infected cells by interacting with nuclear pore complex components of the host cell []. It is also involved in important functions during influenza virus replication. Regulation of viral RNA transcription and replication by NS2 was shown to be an important factor in the adaptation of highly pathogenic avian H5N1 influenza viruses to the mammalian host [].
RanBPM is a scaffolding protein and is important in regulating cellular function in both the immune system and the nervous system. The RanBPM protein contains multiple conserved domains that provide potential protein-protein interaction sites []. This entry represents a domain at the C terminus of RanBPM containing the CT11-RanBPM (CRA) motif. The CRA motif was found to be important for the interaction of RanBPM with fragile X messenger ribonucleoprotein 1 (FMRP), but its functional significance has yet to be determined []. The region comprising this domain contains the CTLH and CRA domains annotated by SMART; however, these may be a single domain, and is referred to as a C-terminal to LisH motif [].
Picornaviruses are single-stranded RNA viruses. Processing of the viral polyprotein by picornains 3C and 2A generates capsid proteins VP0, VP1 and VP3, but VP0 undergoes an autolytic cleavage during virion assembly to generate capsid proteins VP2 and VP4 []. The autolytic cleavage was originally thought to be the action of a serine-type peptidase, but from analogy with the similar autoproteolytic cleavages that are known for capsid proteins from nodaviruses (MEROPS peptidase family N1), tetraviruses (MEROPS peptidase family N2), picobirnaviruses (MEROPS peptidase family N5) and reoviruses (MEROPS peptidase family N7), it is more likely that VP0 is an asparagine-type peptidase; autocatalytic cleavage being promoted by cyclization of a conserved asparagine. .
This domain can be found in uncharacterised proteins in viruses, archaea and bacteria, most notably it is found in YhcG protein from E.coli. This entry represents the C-terminal PDDEXK domain belonging to the PD-(D/E)XK superfamily of nucleases involved in DNA recombination and repair []. Profile HMM analysis identified a relationship between this C-terminal domain of YhcG and endonuclease NucS []. YhcG was identified in association with DNA processing enzymes, including the restriction complexes HsdMRS and McrABC, the integrases IntF and IntS, and the recombinase PinE [].
The structure of TusA (also known YhhP and SirA) consists of an alpha/beta sandwich with a beta-α-β-α-β(2) fold, comprising a mixed four-stranded β-sheet stacked against two α-helices, both of which are nearly parallel to the strands of the β-sheet []. Several uncharacterised bacterial proteins (73 to 81 amino-acid residues in length) that contain a well-conserved region in their N-terminal region show structural similarity to the TusA protein, including the E. coli protein YedF (), and other members of the UPF0033 family.NOTE: TusA was previously known as SirA, but should not be confused with the sporulation inhibitor of replication protein SirA () or with the LuxR/UhpA family response regulator , also known as SirA.
This entry describes the conserved N-terminal region of a variable length protein family associated with laterally transfered regions flanked by markers of conjugative plasmid integration and/or transposition. Most members of the family have the lipoprotein signal peptide motif. A member of the family from a pathogenicity island in Salmonella enterica subsp enterica serovar Dublin strain was designated PilL for nomenclature consistency with a neighbouring gene for the pilin structural protein PilS. However, the species distribution of this protein family tracks much better with markers of conjugal transfer than with markers of PilS-like pilin structure.
This entry represents the L12 protein of the large (50S) subunit of the archaeal ribosome. Archaeal L12 is functionally equivalent to L7/L12 in bacteria and the P1 and P2 proteins in eukaryotes. L12 is homologous to P1 and P2 but is not homologous to bacterial L7/L12. It is located in the L12 stalk, with proteins L10, L11, and 23S rRNA. In several mesophilic and thermophilic archaeal species, the binding of 23S rRNA to protein L11 and to the L10/L12p pentameric complex was found to be temperature-dependent and cooperative [].
Members of this family are similar to the protein product of ORF-3 () found on plasmid pRiA4 in the bacterium Agrobacterium rhizogenes. This plasmid is responsible for tumourigenesis at wound sites of plants infected by this bacterium, but the ORF-3 product does not seem to be involved in the pathogenetic process []. Other proteins found in this family are annotated as being putative TnpR resolvases (, ), but no further evidence was found to back this. Moreover, another member of this family is described as a probable lexA repressor () and in fact carries a LexA DNA binding domain (), but no references were found to expand on this.
This enzyme is proposed here to be a form of aspartate 1-decarboxylase, pyridoxal-dependent, that represents a non-orthologous displacement to the more widely distributed pyruvoyl-dependent form (). Aspartate 1-decarboxylase makes beta-alanine, used usually in pathothenate biosynthesis, by decarboxylation from asparatate. A number of species with the PanB and PanC enzymes, however, lack PanD. This protein family occurs in a number of Proteobacteria that lack PanD. This enzyme family appears to be a pyridoxal-dependent enzyme (see ). The family was identified by Partial Phylogenetic Profiling; members in Geobacter sulfurreducens, Geobacter metallireducens, and Pseudoalteromonas atlantica are clustered with the genes for PanB and PanC. We suggest the gene symbol panP (panthothenate biosynthesis enzyme, Pyridoxal-dependent).
This domain of unknown function is found in Focadhesin from animals and RST1 (RESURRECTION 1) from plants. Focadhesin (FOCAD) is a focal adhesion protein with potential tumour suppressor function in gliomas []. RST1 was originally identified in a genetic screen for factors involved in the biosynthesis of epicuticular waxes []. Later, RST1 and RST1 INTERACTING PROTEIN (RIPR) have been shown to act as cofactors of the cytoplasmic exosome and the Ski complex in plants []. RST1 is involved in the suppression of siRNA-mediated silencing of transgenes and certain endogenous transcripts [].
The chloroplast NADH dehydrogenase-like complex (NDH) was first discovered based on its similarity to complex I in respiratory electron transport. However, it seems to be a ferredoxin-dependent plastoquinone reductase rather than an NAD(P)H dehydrogenase. Furthermore, it also comprises a subcomplex on the stromal side of the thylakoid membrane and a lumenal subcomplex []. The chloroplast NDH complex has been divided into four categories: membrane, lumen, A, and B subcomplexes. The subcomplex A and membrane subcomplex are conserved in cyanobacteria, but the subcomplex B and lumen subcomplex are specific to chloroplasts. PNSB4/NDF6 is a subunit of subcomplex B [].
The chloroplast NADH dehydrogenase-like complex (NDH) was first discovered based on its similarity to complex I in respiratory electron transport. However, it seems to be a ferredoxin-dependent plastoquinone reductase rather than an NAD(P)H dehydrogenase. Furthermore, it also comprises a subcomplex on the stromal side of the thylakoid membrane and a lumenal subcomplex []. The chloroplast NDH complex has been divided into four categories: membrane, lumen, A, and B subcomplexes. The subcomplex A and membrane subcomplex are conserved in cyanobacteria, but the subcomplex B and lumen subcomplex are specific to chloroplasts. PNSB5/ NDH18 is a subunit of subcomplex B [, ].
SNI1 was isolated in a screen for negative regulators of NPR1, a transcriptional coactivator of plant pathogen defence gene PR1 []. SNl1 has been shown to cooperate with the transcription repressor CBNAC, which binds to cis-elements on the PR1 promoter, to suppress PR1 expression []. SNI1 also regulates DNA damage sensor proteins RAD17 and ATR, suggesting that DNA damage responses is an intrinsic component of the plant immune responses. SNI1 is a subunit of the Structural Maintenance of Chromosome (SMC) 5/6 complex involved in DNA damage responses [].
This domain can be found in several hypothetical bacterial proteins of around 250 residues in length. The function of this domain is unknown. The structure of this cytoplasmic domain was solved by the Midwest Center for Structural Genomics (MCSG). The structure has been classified as part of the Class-I Glutamine amidotransferase superfamily owing to similarity with other known structures. The monomer combines with itself to form a hexamer, and this hexamer exposes a potential catalytic surface rich in Glu, Asp, Tyr, Ser.Trp and His residues [].
Protein flightless-1 (FliI) was first identified in the Drosophila melanogaster []. It belongs to the Villin/Gelsolin family, whose members are actin-modulating proteins that sever F-actin, cap the barbed ends of actin filaments preventing monomer exchange, and promote the nucleation step of actin polymerisation [].This entry represent FliI and its homologues. FliI may serve as a nuclear receptor coactivator []and is involved in embryonic development []. In mouse fibroblasts it caps actin filaments and localises to focal adhesions, which collectively affect focal adhesion maturation [].
This entry represents proteins from various mammals known as DEPP proteins, which are decidual proteins induced by progesterone.Decidualization of the endometrial stromal cells (ESC) is thought to be stimulated by progesterone and/or cAMP and is crucial for embryo implantation and placentation. Increased expression of Depp was observed in endometria during mid- and late-secretory phases and 1st trimester deciduas. Depp increased the level of phosphorylated Erk and activated the Elk-1 transcription factor in human embryonal kidney 293 cells, suggesting that Depp modulates the effects of progesterone during decidualization and in the decidua by affecting gene expression [].
Nck-associated protein 1 is part of lamellipodial complex that controls Rac-dependent actin remodeling [, ]. It associates preferentially with the first SH3 domain of Nck and is a component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1, NCKAP1/NAP1 and WASF2/WAVE2. It is also a component of the WAVE1 complex composed of ABI2, CYFIP2, C3orf10/HSPC300, NCKAP1 and WASF1/WAVE1. CYFIP2 binds to activated RAC1 which causes the complex to dissociate, releasing activated WASF1. The complex can also be activated by NCK1. Expression of this protein was found to be markedly reduced in patients with Alzheimer's disease [].
Human Equilibrative, Nitrobenzylthioinosine (NBMPR)-sensitive Nucleoside Transporter ENT1 was the first identified member of the ENT family. ENT1 (also known as solute carrier family 29 member 1, SLC29A1) mediates both influx and efflux of nucleosides across the membrane, including adenosine and many anti-cancer nucleoside drugs [, ]. ENT1 has a topology of 11 transmembrane domains (TMDs) with a 6+5 topology in which the first 6 TM forms one bundle, termed the N-domain, and the final 5 TMs forms another bundle, the C-domain, with a hydrophilic loop between TMD6 and TMD7 [, ]. ENT1 -as ENT2- is localised in plasma membranes and is broadly expressed in tissues [, ].
This domain of approximately 100 residues is conserved from plants to humans. It is an anticodon-binding domain of a prolyl-tRNA synthetase []. It is found in Lms12 and homologues. Lsm12 is a putative RNA-binding and regulation protein that might be involved in mRNA degradation or tRNA splicing []. Recently, it was demonstrated that it binds nicotinic acid adenine dinucleotide phosphate (NAADP) that confers NAADP sensitivity to the two pore channel complex (TPCs) by acting as TPC accessory protein necessary for NAADP-evoked Ca2 release []. Therefore, further studies of the potential crosstalk between NAADP signaling and RNA regulation are required.
The S1 domain was originally identified in ribosomal protein S1 but is found in a large number of proteins involved in RNA metabolism. It belongs to the OB-fold family. The structure of the S1 RNA-binding domain from the Escherichia coli polynucleotide phosphorylase has been determined using NMR methods and consists of a five-stranded antiparallel beta barrel. Conserved residues on one face of the barrel and adjacent loops form the putative RNA-binding site [, ].The structure of the S1 domain is very similar to that of cold shock proteins. This suggests that they may both be derived from an ancient nucleic acid-binding protein [].This entry does not include translation initiation factor IF-1 S1 domains.
Proteins of this family are predominantly nucleolar. Myb-binding protein 1A (MYBBP1A) is a transcription regulator that may play an important role in the cellular stress response [, , , ]. This family also includes the fifth essential DNA polymerase (Pol5p) of Schizosaccharomyces pombe (Fission yeast) and Saccharomyces cerevisiae (Baker's yeast) (). Pol5p is localized exclusively to the nucleolus and binds near or at the enhancer region of rRNA-encoding DNA repeating units []. This protein was originally thought to be a DNA polymerase, however, later reseach indicated its involvement in ribosome assembly [, ].
CarBb is the B subunit of 2-aminophenol 1,6-dioxygenase (CarB), which catalyzes the oxidization and subsequent ring-opening of 2-aminophenyl-2,3-diol. It is a key enzyme in the carbazole degradation pathway isolated from bacterial strains with carbazole degradation ability. The enzyme is a heterotetramer composed of two A and two B subunits. CarB belongs to the class III extradiol dioxygenase family, a group of enzymes which use a non-heme Fe(II) to cleave aromaticrings between a hydroxylated carbon and an adjacent non-hydroxylated carbon. Although the enzyme was originally isolated as a meta-cleavage enzyme for 2'-aminobiphenyl-2,3-diol involved in carbazole degradation, it has also shown high specificity for 2,3-dihydroxybiphenyl [, ].
CarBa is the A subunit of 2-aminobiphenyl-2,3-diol 1,2-dioxygenase, which catalyzes the oxidization and subsequent ring-opening of 2-aminophenyl-2,3-diol. It is a key enzyme in the carbazole degradation pathway isolated from bacterial strains with carbazole degradation ability. The enzyme is a heterotetramer composed of two A and two B subunits. CarB belongs to the class III extradiol dioxygenase family, composed of enzymes which use a non-heme Fe(II) to cleave aromatic rings between a hydroxylated carbon and an adjacent non-hydroxylated carbon. Although the enzyme was originally isolated as a meta-cleavage enzyme for 2'-aminobiphenyl-2,3-diol involved in carbazole degradation, the enzyme has also shown high specificity for 2,3-dihydroxybiphenyl [].
The S1 domain was originally identified in ribosomal protein S1 but is found in a large number of RNA-associated proteins. The structure of the S1 RNA-binding domain from the Escherichia coli polynucleotide phosphorylase has been determined using NMR methods and consists of a five-stranded antiparallel beta barrel. Conserved residues on one face of the barrel and adjacent loops form the putative RNA-binding site []. The structure of the S1 domain is very similar to that of cold shock proteins. This suggests that they may both be derived from an ancient nucleic acid-binding protein [].
Clp1 function involves some degree of adenine or guanine nucleotide binding and participates in the 3' end processing of mRNAs in eukaryotes []. Both human Clp1 (hsClp1) and Saccharomyces cerevisiae Clp1 (scClp1) were identified as components of the pre-mRNA 3end-processing machinery. WhereashsClp1 was shown to also be part of the tRNA endonuclease complex, scClp1 exclusively contributes to mRNA maturation and appears to be enzymatically inactive.Clp1 contains three domains, a small N-terminal beta sandwich domain involved in DNA binding [], a C-terminal domain containing a novel alpha/β-fold and a central domain that binds ATP [, ]. This entry represents the short N-terminal domain of the pre-mRNA cleavage complex II protein Clp1.
This entry represents the Orf10 protein of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV). SARS-CoV-2 causes the disease called "coronavirus disease 2019"(COVID-19). Orf10 appears to have no homologous proteins in SARS-CoV and other coronaviruses and is uniquely expressed in SARS-CoV-2 [, , ]. Recently, it was reported that Orf10 suppresses the IFN-I signalling pathway through the interaction with mitochondrial antiviral signalling protein (MAVS), which is degraded via Orf10-induced autophagy pathway. Orf10 interacts with NIX and LC3B and induces mitophagy [].
This entry represents a small clade of dipeptidase enzymes from the Lactobacillaceae, which belong to MEROPS peptidase family M20A. The Lactococcus lactis enzyme has been shown to act on a wide range of dipeptides, but not larger peptides []. The enzyme from Lactobacillus delbrueckii was originally characterised as a Xaa-His dipeptidase, specifically a carnosinase (beta-Ala-His) by complementation of an Escherichia coli mutant. Further study, including the crystallisation of the enzyme, has shown it to also be a non-specific dipeptidase []. This group also includes enzymes from Streptococcus and Enterococcus.
The exocyst is a highly conserved complex composed of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84, which was originally identified in Saccharomyces cerevisiae []. Mammalian homologues of all eight exocyst proteins have been identified []. The exocyst is required for exocytosis; it mediates tethering of the secretory vesicle before docking and fusion with the plasma membrane [].Sec10 (also known as exocyst complex component 5) is a component of the eukaryotic exocyst complex. It modulates the synthesis and delivery of secretory and basolateral plasma membrane proteins [, ], and is necessary for primary ciliogenesis and cystogenesis [, ].
Alkaptonuria (AKU), a rare hereditary disorder, was the first disease to be interpreted as an inborn error of metabolism. The deficiency causes homogentisic aciduria, ochronosis, and arthritis. AKU patients are deficient for homogentisate 1,2 dioxygenase (HGD) (), the enzyme that mediates the conversion of homogentisate to maleylacetoacetate, a step in the catabolism of both tyrosine and phenylalanine. The structure of this protein shows that the enzyme forms a hexamer arrangement comprised of a dimer of trimers. The active site iron ion is coordinated near the interface between the trimers [, ].This group of proteins includes human HDG and homologues from eukaryotes, bacteria and some archaeal species.
This entry describes a family of small cytosolic proteins, about 80 amino acids in length, in which the eight invariant residues include three His residues and two Cys residues. Two pairs of these invariant residues occur in motifs HxH (where x is A or G) and CxH, both of which suggest metal-binding activity. This protein family was identified by searching with a phylogenetic profile based on an anaerobic sulphatase-maturase enzyme, which contains multiple 4Fe-4S clusters. The linkages by phylogenetic profiling and by iron-sulphur cluster-related motifs together suggest this protein may be an accessory protein to certain maturases in sulphatase/maturase systems.
This entry represents an conserved site found in members of a structural superfamily of Schiff base-forming aldolases that catalyse reactions indifferent biological pathways. This superfamily includes members such as dihydrodipicolinate synthase (DHDPS), N-acetylneuraminate lyase (NAL) and 2-keto-3-deoxygluconate aldolase (KDG aldolase) []. One of the Escherichia coli proteins containing this site, dapA (), was first identified as dihydrodipicolinate synthase (DHDPS) []. Later, it has been identified as 4-hydroxy-tetrahydrodipicolinate synthases () []. Among the putative DHDPS genes annotated in the A. tumefaciens genome, dapA7 gene product has been shown to possess DHDPS enzyme activity and is allosterically inhibited by lysine [].
This entry represents an active site found in members of a structural superfamily of Schiff base-forming aldolases that catalyse reactions indifferent biological pathways. This superfamily includes members such as dihydrodipicolinate synthase (DHDPS), N-acetylneuraminate lyase (NAL) and 2-keto-3-deoxygluconate aldolase (KDG aldolase) []. One of the Escherichia coli proteins containing this site, dapA (), was first identified as dihydrodipicolinate synthase (DHDPS) []. Later, it has been identified as 4-hydroxy-tetrahydrodipicolinate synthases () []. Among the putative DHDPS genes annotated in the A. tumefaciens genome, dapA7 gene product has been shown to possess DHDPS enzyme activity and is allosterically inhibited by lysine [].
The SWIRM domain is a small α-helical domain of about 85 amino acid residues found in eukaryotic chromosomal proteins. It is named after the proteins SWI3, RSC8 and MOIRA in which it was first recognised. This domain mediates protein-protein interactions in the assembly of chromatin-protein complexes [, ]. The yeast SWI3 SWIRM structure revealed that it forms a four-helix globular domain containing a helix-turn-helix motif [].The SWIRM domain can be linked to different domains, such as the ZZ-type zinc finger (), the Myb DNA-binding domain (), the HORMA domain (), the amino-oxidase domain, the chromo domain (), and the JAB1/PAD1 domain.
This entry represents the UPF0234 family of uncharacterised proteins, which includes YajQ.In Pseudomonas syringae, YajQ functions as a host protein involved in the temporal control of bacteriophage Phi6 gene transcription. It has been shown to bind to the phage's major structural core protein P1, most likely activating transcription by acting indirectly on the RNA polymerase. YajQ may remain bound to the phage particles throughout the infection period [, ]. Earlier, YajQ was characterized as a putative nucleic acid-binding protein based on the similarity of its (ferredoxin-like) three-dimensional topology with that of RNP-like RNA-binding domains [, ].
The entry represents the PDZ-binding domain of Harmonin-binding protein USHBP1 (also known as MCC2, mutated in colon cancer-2). USHBP1 has high homology to tumour suppressor MCC1 (mutated in colon cancer-1).MCC2 protein binds the first PDZ domain of AIE-75 (also known as Harmonin) with its C-terminal amino acids -DTFL. A possible role of MCC2 as a tumour suppressor has been put forward. The carboxyl terminus of the predicted protein was DTFL which matched the consensus motif X-S/T-X-phi (phi: hydrophobic amino acid residue) for binding to the PDZ domain of AIE-75 [, ].
Cpn20 is a functional homologue of the cpn10 (also known as GroES) co-chaperonin, but it consists of two cpn10-like units joined head-to-tail by a short chain of amino acids. This double protein is unique to plastids and was shown to exist in plants as well plastid-containing parasites []. Cpn20 seems to function as a co-chaperone, along with cpn60, and in certain cases is essential for the discharge of biologically active proteins from cpn60 []. It might be an iron chaperone for superoxide dismutase in activating iron superoxide dismutase (FeSOD) [].
The delineation of this family was based originally, in part, on a discussion and neighbour-joining phylogenetic study []of archaeal and other proteins homologous to the alpha, beta, and delta subunits of eukaryotic initiation factor 2B (eIF-2B), a five-subunit molecule that catalyses GTP recycling for eIF-2 []. Later, this group of archaeal proteins have been shown to function as ribulose-1,5 bisphosphate isomerases (R15Pi). Thermococcus kodakarensis R15Pi, also known as TK0185, converts d-ribose 1,5-bisphosphate into ribulose 1,5-bisphosphate, providing the substrate for archaeal ribulose-1,5-bisphosphate carboxylase/oxygenases. Its structure has been revealed [].
This superfamily represents the HTH (helix-turn-helix) central domain from the metalloprotease IrrE, a central regulator of DNA damage repair in Deinococcaceae []. It is folded in a three-helix bundle, with the second and third helices forming the HTH motif. The IrrE HTH domain shows a high level of structural similarity to HTH domains of the Lrp/AsnC transcriptional regulatory family, although it is not located as expected at either C- or N-terminal of the protein. Its central location was suggested to endow it with some specific properties [].The domain is also found at the C-terminal of the catalytic domain of the protein ImmA (MEROPS identifier M78.001), a metallopeptidase containing an HEXXH zinc-binding motif.
SurE is one of the several proteins that is expressed when bacterial cells are subjected to environmental stresses and in the stationary growth phase of bacteria [, ]. In E. coli, surE is next to pcm, an L-isoaspartyl protein repair methyltransferase that is also required for stationary phase survival. It was originally predicted to be an acid phosphatase, however, subsequent work showed this is not the case []. SurE has been shown to possess phosphatase activity and appears to be specific to nucleoside monophosphates []. In E. coli, Thermotoga maritima, and Pyrobaculum aerophilum SurE acts strictly on nucleoside 5'- and 3'-monophosphates.
This superfamily includes the F1 beta subunit of ATP synthase.F-type ATPases have 2 components, CF1 - the catalytic core - and CF0 - the membrane proton channel. CF1 has five subunits: alpha3, beta3, gamma1, delta1, epsilon1. CF0 has three main subunits: a, b and c.The NMR solution structure of the protein in SDS micelles was found to contain two helices, an N-terminal amphipathic α-helix and a C-terminal α-helix separated by a large unstructured internal domain. The N-terminal α-helix is the Tom20 receptor binding site whereas the C-terminal α-helix is located upstream of the mitochondrial processing peptidase cleavage site [].
RbsD is a component of the ribose operon. It was originally thought to be a high affinity ribose transport protein, but further analysis []shows that it is a D-ribose pyranase . It catalyzes the interconversion of beta-pyran and beta-furan forms of D-ribose. It also catalyzes the conversion between beta-allofuranose and beta-allopyranose.FucU is a component of the fucose operon and is a L-fucose mutarotase , involved in the anomeric conversion of L-fucose. It also exhibits a pyranase activity for D-ribose [].Both have been classified in the RbsD/FucU family of proteins. Members of this family are ubiquitous having been found in organisms from eubacteria to mammals.
This entry represents Tuberoinfundibular peptide of 39 residues (TIP39), which is a potent and selective agonist of the parathyroid hormone 2 receptor (PTH2R) []. In human, TIP39 expression was detected by RT-PCR in the brain, trachea, fetal liver, kidney and heart. In the brain, TIP39 is expressed in only three sites, the medial and lateral parts of the subparafascicular area in the caudal thalamus, and the medial paralemnsical nucleus in the lateral pons []. The TIP39-PTH2R system is a unique neuropeptide-receptor system that plays a role in limbic, endocrine, viscerosensory, and auditory functions [].
CD20, also known as membrane-spanning 4-domains subfamily A member 1 (MS4A1), was the first B cell differentiation antigen identified. CD20 is highly expressed by B cell lymphocytes throughout their development, but is absent on the hematopoietic stem cells []. Anti-CDC20 antibodies are commonly used for the treatment of B-cell lymphoid malignancies [].The function of CD20 remains unclear. It may be involved in calcium signalling downstream of B cell antigen receptor activation [, ]. CD20 has a been shown to play a central role in the generation of T cell-independent antibody responses [].
This entry represents mitogen-activated protein kinase kinase kinase 7 (MAP3K7, also known as TAK-1), which is a component of a protein kinase signal transduction cascade, acting as a mediator of TGF-beta signal transduction. MAP3K7 stimulates NF-kappa-B (NFKB) activation and the p38 MAPK pathway through the phosphorylation and activation of several MAP kinase kinases []. MAP3K7 binds both upstream activators and downstream substrates in multi-molecular complexes. This entry also includes the C. elegans human homologue MOM-4 [], which is part of the Wnt signaling pathway, essential for cell fate specification during embryo development.A small deletion of MAP3K7 and four other genes was found to be strongly associated with high-grade prostate cancers [].
Mutations in the LGI/EPT gene can result in a special form of epilepsy, autosomal dominant lateral temporal epilepsy. The Epitempin protein (also known as Leucine-rich glioma-inactivated protein) was seen to contain a 130 amino acid repeat in its C-terminal section, although a sub-domain of 50 amino acids has now been further defined within this. The architecture and structural features of this repeat make it a likely member 7-bladed β-propeller fold [].This protein has now been found in a number of proteins associated with neurological disorders suggesting that it may play a role in the development of epilepsy and other related conditions [].
This entry represents the odorant response abnormal protein 4 (ODR-4)-like proteins from animals and plants. In C.elegans, ODR-4 and ODR-8 are required for localising a subset of odorant GPCRs to the cilia of olfactory neurons []. Olfactory receptors (ORs) are synthesised in endoplasmic reticulum of the olfactory neurons, trafficked to the cell surface membrane and transported to the tip of the olfactory cilium, where they bind with odorants. Various accessory proteins are required for proper targetting of different ORs to the cell membrane. ODR-4 was the first accessory protein to be described. ODR-4 plays a role in nociceptive neurons to mediate avoidance of high oxygen [].
Chisel protein plays a role in the regulatory network through which muscle cells coordinate their structural and functional states during growth, adaptation, and repair. The X-linked gene Chisel (Csl/Smpx) was first found expressed selectively in human cardiac and skeletal muscle cells []. It is expressed in embryos in sub-regions of the developing heart corresponding to the future chamber myocardium and in developing skeletal muscles []. It is a potential target of the cardiac homeodomain transcription factor Nkx2-5 []. It localises to the costameric cytoskeleton of muscle cells through its association with focal adhesion proteins, where it may participate in regulating the dynamics of actin through the Rac1/p38 kinase pathway [].
This class of bacteriocins was previously described as class V. The members include gassericin A, acidocin B and butyrovibriocin AR10, all of which are hydrophobic cyclical structures []. The N-and C-termini are covalently linked, and the circular molecule is resistant to several proteases and peptidases []. The immunity protein that protects Lactobacillus gasseri from the toxic effects of its bacteriocin, gassericin A, has been identified. It is found to be a small positively-charged hydrophobic peptide of 53 amino acids containing a putative transmembrane segment []- a structure unlike that of the more common immunity proteins as found in .
F-type ATPases have 2 components, CF1 - the catalytic core - and CF0 - the membrane proton channel. CF1 has five subunits: alpha3, beta3, gamma1, delta1, epsilon1. CF0 has three main subunits: a, b and c. This entry represents the beta subunit of the F1 component.The NMR solution structure of the protein in SDS micelles was found to contain two helices, an N-terminal amphipathic α-helix and a C-terminal α-helix separated by a large unstructured internal domain. The N-terminal α-helix is the Tom20 receptor binding site whereas the C-terminal α-helix is located upstream of the mitochondrial processing peptidase cleavage site [].
This superfamily contains mainly functionally uncharacterised proteins found in bacteria, typically between 99 to 124 amino acids in length.The most representative domain was characterised in Rv0543c - a monomeric bundle of five α-helices rigidly held together by a largely conserved group of hydrophobic amino acid side chains. The fold observed for Rv0543c may be unique for Rv0543c and the other members of the DUF3349 superfamily. According to literature, the DUF3349 proteins are predicted to be good drug targets because they are predominantly in the Mycobacterium and Rhodococcus bacterial species [].
Erbin (also known as Protein LAP2), was first identified as an adaptor for the receptor ERBB2/HER2 in epithelia []. It is involved in inhibition of several intracellular signalling pathways, such as Ras-mediated activation of extracellular signal-regulated kinase (ERK), nuclear factor kappaB, and transforming growth factor beta signalling pathways [].It contains an N-terminal domain with 16 leucine-rich repeats and a C-terminal PDZ domain. Through its amino-terminal region, Erbin disrupts Ras-Raf interaction by preventing the Ras-binding protein Shoc2 from binding to Ras, and thus acting as a tumour suppressor [].
Outer membrane protein (OMP) assembly factor BamB is part of the outer membrane protein assembly Bam complex (composed of the outer membrane protein BamA, and four lipoproteins BamB, BamC, BamD and BamE), which is involved in assembly and insertion of β-barrel proteins into the outer membrane [, , , , ]. Although BamB is not essential in E. coli, it serves an important function in the BAM complex, significantly increasing the folding efficiency of some OMPs in vivo and in vitro. It was suggested that BamB serves as a scaffolding protein in the Bam complex by optimally orienting the flexible periplasmic domain of BamA for interaction with other BAM components and chaperones [].
ASZ1 (Ankyrin, SAM, leucine Zipper), also known as GASZ (Germ cell-specific Ankyrin, SAM, leucine Zipper), is a potential protein-protein interaction domain []. Proteins containing this domain are involved in the repression of transposable elements during spermatogenesis, oogenesis, and preimplantation embryogenesis. They support synthesis of PIWI-interacting RNA via association with some PIWI proteins, such as MILI and MIWI. This association is required for initiation and maintenance of retrotransposon repression during the meiosis. In mice lacking ASZ1, DNA damage and delayed germ cell maturation was observed due to retrotransposons releasing from their repressed state [, ].
Envoplakin belongs to the plakin family of cytolinker proteins, which also includes desmoplakin, plectin, periplakin and BPAG1 (bullous pemphigoid antigen) []. It was originally identified as components of the cornified envelope (CE) [, ]. It is also found in the desmosomes of keratinocytes and other epithelial cells []. Envoplakin and periplakin can form stable heterodimers that localise to desmosomes and the plasma membrane in a manner dependent on the periplakin N terminus []. The C termini of envoplakin and periplakin bind intermediate filaments, and this interaction may provide the link between the cytoskeleton and the CE that confers mechanical stability to corneocytes [, ].
Asp23 was identified as an alkaline shock protein expressed in a sigmaB-dependent manner in Staphylococcus aureus () []. Following an alkaline shock, Asp23 accumulates in the soluble protein fraction of the S. aureus cell. Asp23 is one of the most abundant proteins in the cytosolic protein fraction of stationary S. aureus cells, with a copy-number of >25000 per cell. It is linked to the staphylococcal cell membrane and anchored there by AmpA. The overall function for the family is thus a cell envelope-related one in Gram-positive bacteria. [].
The majority of proteins in this group contain a single copy of this domain, though it is also found as a repeat. A strongly conserved histidine and a aspartate suggest that the domain has an enzymatic function. This entry also covers what was previously known as the DGPF domain (COG3795), named after the most conserved motif in the alignment. Although its function is unknown it is found fused to a sigma-70 factor family domain in , suggesting that this domain may plays a role in transcription initiation.
This family represents PNPLA3 (patatin-like phospholipase domain-containing protein 3) from mammals, also known as ADPN (adiponutrin) or iPLA2-epsilon (calcium-independent phospholipase A2). PNPLA3 is a triacylglycerol lipase that mediates triacylglycerol hydrolysis in adipocytes and is an indicator of the nutritional state. Human adiponutrins are bound to the cell membrane of adipocytes and show transacylase, TG hydrolase, and PLA2 activity [, , ]. In murine models, PNPLA3 was found to be involved in the hepatic metabolism of triglycerides and in the regulation of systemic glucose homeostasis [].
This entry represents a group of E3 ubiquitin-protein ligases, including UBR1, UBR2 and UBR3. They are part of the N-end rule pathway []. They recognize and bind to proteins bearing specific N-terminal residues, leading to their ubiquitination and subsequent degradation [, ].The UBR1 protein was shown to bind specifically to proteins bearing N-terminalresidues that are destabilising according to the N-end rule, but not tootherwise identical proteins bearing stabilising N-terminal residues []. UBR1 contains an N-terminal conserved region (the UBR-type zinc finger) which is also found in various proteins implicated in N-degron recognition [].
The sequences in this entry belong to the superfamily of NAD-dependent epimerases and dehydratases which typically act on nucleotide-sugar substrates. The genes encoding proteins in this entry are generally in the same locus as genes involved in the biosynthesis and elaboration of hopene, the cyclization product of the polyisoprenoid squalene. This gene and its association with hopene biosynthesis in Zymomonas mobilis has been noted in the literature where the gene symbol hpnA was assigned []. Hopanoids are known to be components of the plasma membrane and to have polar sugar head groups in Z. mobilis and other species.
Sensor histidine kinase RcsC forms part of a phosphorelay signal transduction pathway with RcsD and RcsB. RcsC functions as a membrane-associated protein kinase that phosphorylates RcsD in response to environmental signals []. The phosphoryl group is then transferred to the response regulator RcsB. The system controls transcription of numerous genes. It was first identified by its role in the regulation of capsular polysaccharide or colanic acid synthesis [, , ]. Pathways regulated by the Rcs system include maintenance of cell wall integrity, cell division,motility, and virulence [, , ]. A novel signaling pathway that depends on RcsC, but independent of RcsD and RcsB, has also been described [].
Otoraplin, also known as MIAL (MIA-like), is specifically expressed in the cochlea and the vestibule of the inner ear and may contribute to inner ear dysfunction in humans []. It is a member of the MIA family. MIA (melanoma inhibitory activity) family members include MIA, MIAL, MIA2, and MIA3 (also called TANGO). MIA was found to be strongly expressed and secreted by malignant melanomas. It contains a domain that adopts a Src Homology 3 (SH3) domain-like fold; however, it contains an additional antiparallel beta sheet and two disulfide bonds compared to classical SH3 domains. Unlike classical SH3 domains, MIA does not bind proline-rich ligands [, ].
Transgelin belongs to the calponin family, whose members have an N-terminal calponin homology domain (CH) and a C-terminal calponin-like repeat. Transgelin (also known as SM22) is an actin binding protein localised to the cytoskeletal apparatus []. Transgelin is required in agonist-induced smooth muscle contraction and is involved in cell migration [, ]. It has tumour suppressive functions in certain cells [, ]. Closely related to transgelin is transgelin-3 (TAGLN3), also known as neuronal protein NP25 []or NP22 []. It was identified as a neuron-specific protein and may have a role in the regulation of neurite growth [].
This is the SAM pointed domain of FLI-1 (Friend Leukemia Integration) subfamily of ETS transcriptional regulators. It is a putative protein-protein interaction domain. The FLI-1 protein participates in regulation of cellular differentiation, proliferation, and survival [, ]. The Fli-1 gene was initially described in Friend virus-induced erythroleukemias as a site for virus integration. It is highly expressed in hematopoietic tissues and at lower level in lungs, heart, and ovaries. Fli-1 is a proto-oncogene implicated in Ewing's sarcoma and erythroleukemia [, ]. Members of this family are potential targets for cancer therapy [].
This entry represents the SAM (sterile alpha motif) domain of EPH-A6 (Ephrin type-A receptor 6), a receptor tyrosine kinase. It is a C-terminal potential protein-protein interaction domain located in the cytoplasmic region of EPH-A6 receptors and appears to mediate cell-cell initiated signal transduction []. Eph-A6 gene is preferentially expressed in the nervous system. EPH-A6 receptors are involved in primate retina vascular and axon guidance, and in neural circuits responsible for learning and memory []. EphA6 gene was significantly down regulated in colorectal cancer and in malignant melanomas. It is a potential molecular marker for these cancers [, ].
Secreted Ly-6/uPAR-related protein 1 (SLURP-1) belongs to the Ly-6/uPAR superfamily of receptor and secreted proteins. SLURP1 has antitumor activity. It was found to be a marker of late differentiation of the skin. SLURP1 is implicated in maintaining the physiological and structural integrity of the keratinocyte layers of the skin [, , ]. Defects in SLURP1 are a cause of Mal de Meleda (MDM); also known as keratosis palmoplantaris transgradiens of Siemens. MDM is a rare autosomal recessive skin disorder, characterised by diffuse transgressive palmoplantar keratoderma with keratotic lesions extending onto the dorsa of the hands and the feet (transgrediens) [, ].
Picornaviruses are single-stranded RNA viruses. Processing of the viral polyprotein by picornains 3C and 2A generates capsid proteins VP0, VP1 and VP3, but VP0 undergoes an autolytic cleavage during virion assembly to generate capsid proteins VP2 and VP4 []. The autolytic cleavage was originally thought to be the action of a serine-type peptidase, but from analogy with the similar autoproteolytic cleavages that are known for capsid proteins from nodaviruses (MEROPS peptidase family N1),tetraviruses (MEROPS peptidase family N2), picobirnaviruses (MEROPS peptidase family N5) and reoviruses (MEROPS peptidase family N7), it is more likely that VP0 is an asparagine-type peptidase; autocatalytic cleavage being promoted by cyclization of a conserved asparagine. .
This entry consists of ABC transporter substrate-binding proteins associated with urea transport and metabolism. This family includes UrtA from Cyanobacteria, which is encoded in an operon typically found adjacent to urease genes. It was shown in that disruption leads to the loss of high-affinity urea transport activity []. It also includes the periplasmic component (FmdD) of an active transport system for short-chain amides and urea (FmdDEF), found in Methylophilus methylotrophus []. These proteins tend to have the twin-arginine signal for Sec-independent transport across the plasma membrane.
This is the C-terminal domain found in components of the gamma-tubulin complex proteins (GCPs). Family members include spindle pole body (SBP) components such as Spc97 and Spc98 which function as the microtubule-organizing centre in yeast []. Furthermore, family members such as human GCP4 (gamma-tubulin complex component 4) have been structurally elucidated (). Structure-based sequence analysis revealed the existence of an exposed surfacearea conserved in all human GCPs and in GCP4 orthologues. This area is located in the C-terminal domain of GCP4, which was confirmed in vitro to bind directly to gamma-tubulin. Sequence alignment of human GCPs based on the GCP4 structure helped delineate conserved regions in the N- and C-terminal domains [].
This entry defines the ligand-binding and dimerisation domain of the bacterial regulatory protein AraC and other HTH-type transcriptional regulators.The crystal structure of the arabinose-binding and dimerisation domain of the Escherichia coli gene regulatory protein AraC was determined in the presence and absence of L-arabinose. The arabinose-bound molecule shows that the protein adopts an unusual fold, binding sugar within a beta barrel and completely burying the arabinose with the amino-terminal arm of the protein. Dimer contacts in the presence of arabinose are mediatedby an antiparallel coiled-coil. In the uncomplexed protein, the amino-terminal arm is disordered, uncovering the sugar-binding pocket and allowing it to serve as an oligomerization interface [].
Wnt morphogens control embryonic development and homeostasis in adult tissues. In vertebrates the N-terminal WIF domain (WIF-1WD) of Wnt inhibitory factor 1 (WIF-1) binds Wnt ligands.This entry represents the WIF domain, it is found in the RYK tyrosine kinase receptors and WIF the Wnt-inhibitory-factor. The domain is extracellular and contains two conserved cysteines that may form a disulphide bridge. This domain is Wnt binding in WIF, and it has been suggested that RYK may also bind to Wnt []. The WIF domain of WIF-1 was suggested to have a function in inhibiting Wnt signalling [].
Members of this family occur strictly in the genus Mycoplasma, average 1050 in length with little length variability, have an N-terminal signal sequence, and exhibit no detectable sequence similarity to any characterised protein. Up to four tandem copies occur in some Mycoplasma (e.g. M. putrefaciens KS1). Incorrect inclusion of a 57-amino acid stretch of one family member in , for a helix-turn-helix transcriptional regulator in several E. coli phage, has caused many members of this family to be annotated, in error, as GnsA/GnsB family proteins. The name STREFT (Secreted Thousand Residue Frequently Tandem) protein was suggested by TIGRfam as a distinctive name to spread and replace the incorrect GnsA/GnsB designation.
The 26S proteasome is a large enzymatic complex (composed of the 20S core particle (CP) and the 19S regulatory particle (RP)) that degrades ubiquitinated proteins in eukaryotic cells [].This entry represents 26S proteasome non-ATPase regulatory subunit 10 (also known as Gankyrin or p28, gene name PSMD10, or NAS6 in yeast). Gankyrin was initially thought to be a subunit of the 19S RP, however it has since been shown to associate transiently with the RP, acting as a chaperone during proteasome assembly. Specifically, it has been shown to interact with 26S proteasome regulatory subunit 6B (RPT3, PSMC4) []. Gankyrin (an ankyrin-repeat protein) is also reported as an oncoprotein involved in hepatocarcinogenesis [].
Aminobutyraldehyde dehydrogenase functions in the putrescine degradation pathway. It catalyses the oxidation of 4 aminobutyraldehyde to 4 aminobutyrate, a neurotransmitter. YdcW encodes gamma-aminobutyraldehyde dehydrogenase (ABALDH) in the wild-type Escherichia coli (strain K12). It is a tetramer and when coupled with YgjG putrescine transaminase in vitro, putrescine was converted into gamma-aminobutyric acid []. The tetramer is composed of identical subunits. YdcW can also oxidize N-alkyl medium-chain aldehydes, but with a lower catalytic efficiency []. The same enzyme from Arthrobacter sp. utilises both NAD+ and NADP+ as coenzymes. It functions optimally at pH 8.0 [].
This entry represents a domain superfamily found in GMP-PDE delta subunit and related proteins. GMP-PDE delta subunit was originally identified as a fourth subunit of rod-specific cGMP phosphodiesterase (PDE) (). The precise function of PDE delta subunit in the rod specific GMP-PDE complex is unclear. In addition, PDE delta subunit is not confined to photoreceptor cells but is widely distributed in different tissues. PDE delta subunit isthought to be a specific soluble transport factor for certain prenylated proteins and Arl2-GTP a regulator of PDE-mediated transport [].
Salmonella typhimurium contains a 90kb plasmid that is associated withvirulence. This plasmid encodes at least 6 genes needed by thebacterium for invading host macrophages during infection. These includethe 70kDa mkaA protein [], a recognised virulence factor, and more recently described, four spv genes under the control of a regulator [].Deletion studies on the virulence plasmid have shown that an open reading frame encoding a 28kDa protein was needed for successful invasion of the host. This protein, designated mkfA [], VRP4 []or VirA []by differentgroups, is utilised by the microbe upon entry into macrophages, although the exact mechanism is unclear.
This entry represents Oxidized purine nucleoside triphosphate hydrolase (8ODP, also known as 7,8-dihydro-8-oxoguanine triphosphatase and MHT1), and similar Nudix hydrolase domain-containing proteins from bacteria, eukaryots and archaea. This protein has a significant hydrolase activity toward 2-oxo-ATP, 8-oxo-dGTP and 8-oxo-dATP and catalyzes the hydrolysis of methylated purine nucleoside triphosphate preventing their integration into DNA [, , ]. It was originally considered to play an important role as sanitizer of the oxidized nucleotide pool [, ]. However, later studies indicate that NUDT1 plays a redundant role in eliminating oxidized nucleotides and that it is not essential for cancer cell proliferation and survival [, ].
Flavodoxins are electron-transfer proteins that function in various electron transport systems. Flavodoxins bind one FMN molecule, which serves as a redox-active prosthetic group []and are functionally interchangeable with ferredoxins. They have been isolated from prokaryotes, cyanobacteria, and some eukaryotic algae.This entry represents a conserved site, indicative of the N-terminal region of Flavodoxin proteins that spans an FMN-binding site [].This conserved site is also found in Protoporphyrinogen IX dehydrogenase (quinone), encoded by the gene hemG in gamma-proteobacteria. Protoporphyrinogen IX dehydrogenase (quinone) is a member of a class of the long chain flavodoxin family, and was found to show protoporphyrinogen oxidase activity [].
This domain is found in many multi-domain enzymes which synthesize peptide antibiotics. This domain catalyses a condensation reaction to form peptide bonds in non-ribosomal peptide biosynthesis. It is usually found to the carboxy side of a phosphopantetheine binding domain (pp-binding). This domain was described as a pseudo-dimer of two lobes, the N-terminal lobe (N-lobe) and the C-terminal lobe (C-lobe), each of them consisting of one large central beta sheet, flanked by predominantly α-helices. The active site motif, HHxxxDG, is located in a loop that connects the central strand of the N-lobe and one of its long α-helices. Mutations in the HHXXXDG motif abolish the domain activity [, ].
Proteins containing this domain were originally annotated as basic membrane lipoproteins []. However, several proteins containing this domain were later predicted as ABC transporter substrate-binding proteins, such as PnrA (also known as TmpC or TP0319) and RfuA (also known as Tpn38 or TP0298) from Treponema pallidum. PnrA transports purine nucleosides [], while RfuA transports riboflavin []. Proteins containing this domain also include Med from Bacillus subtilis. Med was annotated as a transcriptional activator protein that regulates comK []. This domain can also found at the N terminus of glutamate receptor-like proteins from Dictyostelium (slime mold) [].
SPE-4 peptidase (MEROPS identifier A22.012) is an intramembrane, aspartic endopeptidase characterized from Caenorhabditis elegans. Swapping the active site domain of presenilin 1 with SPE-4 resulted in a protein that could process the beta-amyloid protein precursor but not Notch, and the difference in substrate recognition was shown by site-directed mutagenesis to depend on the nature of a residue in the GxGD motif that includes the active site aspartic acid []. SPE-4 is essential for the activation of sperm cells, and in a naturally occurring mutant known as hc196, spermatocytes are defective, and spermatids are activated prematurely [].
Twist was first identified in Drosophila melanogaster as a gene crucial for proper gastrulation and mesoderm formation []. Twist is a basic helix-loop-helix transcription factor that acts in a signalling cascade that initiates mesoderm development during gastrulation when it is involved in regulating the process of epithelial-mesenchymal transition (EMT) [, ].The bHLH (basic Helix-Loop-Helix) proteins contain the bHLH domain that is approximately 60 amino acids long and consists of a DNA-binding basic region followed by two a-helices separated by a variable loop region (HLH). The HLH domain promotes dimerisation, allowing the formation of homo- or heterodimeric complexes between different family members. Many bHLH proteins have been shown to act as transcriptional regulators [].
CASTOR1 (Cytosolic arginine sensor for mTORC1 subunit 1) has been identified as the cytosolic arginine sensor for the mTORC1 pathway. In the absence of arginine, CASTOR1 binds to GATOR2 and inhibits mTORC1 signaling; whereas in the presence of arginine, CASTOR1 interacts with arginine and no longer associates with GATOR2. The arginine sits in a pocket between the N-terminal domain (NTD) and the C-terminal domain (CTD) of CASTOR1. The CASTOR1-NTD on the opposite side of the arginine-binding site was identified to mediate direct physical interaction with its downstream effector GATOR2, via GATOR2 subunit Mios [].
