This entry includes NYAP1 and NYAP2 from neuronal tyrosine-phosphorylated adaptor for the PI 3-kinase (NYAP) family (consists of NYAP1, NYAP2, NAP3/Myosin16). NYAPs activate PI3K in PI3K pathway, whichis a fundamental pathway for various cellular events in neurons. They also interact with components of the WAVE1 complex, which mediates actin cytoskeleton remodeling through Arp2/3 complex. It was suggested that NYAPs connect PI3K activation to WAVE1 signalling in neurons[].
NYAP1 belongs to the neuronal tyrosine-phosphorylated adaptor for the PI 3-kinase (NYAP) family, which consists of NYAP1, NYAP2, NAP3/Myosin16. NYAPs activate PI3K in PI3K pathway, which is a fundamental pathway for various cellular events in neurons. They also interact with components of the WAVE1 complex, which mediates actin cytoskeleton remodeling through Arp2/3 complex. It was suggested that NYAPs connect PI3K activation to WAVE1 signalling in neurons[].
Deformed epidermal autoregulatory factor-1 (DEAF-1) was first isolated in Drosophila melanogaster as a novel DNA-binding protein []. Since then, several orthologues in mammals have been identified. In Drosophila, DEAF-1 plays an important role in embryonic development, particularly in the segmentation stage following cuticle secretion. In mammals it regulates different processes, including epithelial cell proliferation and side-branching in the mammary gland []and it is required for neural tube closure and skeletal patterning [].
This superfamily consists of several invasion associated locus B (IalB) proteins and related sequences. IalB is known to be a major virulence factor in Bartonella bacilliformis where it was shown to have a direct role in human erythrocyte parasitism. IalB is up-regulated in response to environmental cues signalling vector-to-host transmission. Such environmental cues would include, but not be limited to, temperature, pH, oxidative stress, and haemin limitation. It is also thought that IalB would aide B. bacilliformis survival under stress-inducing environmental conditions [].
SRP-independent targeting protein 3 (SND3, previously known as PHO88) is localized to the endoplasmic reticulum (ER). SND3 works together with SND1 and SND2; these proteins function in parallel with the SRP and GET pathways to target a broad range of substrates to the ER. The SND proteins constitute an alternative targeting route to the ER []. SND3/PHO88 was first identified as a Saccharomyces cerevisiae protein involved in inorganic phosphate transport [].
Translins are DNA-binding proteins that specifically recognise consensus sequences at the breakpoint junctions in chromosomal translocations, mostly involving immunoglobulin (Ig)/T-cell receptor gene segments. They seem to recognise single-stranded DNA ends generated by staggered breaks occuring at recombination hot spots []. Translin folds into an α-α superhelix, consisting of two curved layers of alpha/alpha topology [, ].This entry also includes translin-associated protein X (TRAX), which was found to interact with translin [, ].
The S4 domain is a small domain consisting of 60-65 amino acid residues that was detected in the bacterial ribosomal protein S4, eukaryotic ribosomal S9, two families of pseudouridine synthases, a novel family of predicted RNA methylases, a yeast protein containing a pseudouridine synthetase and a deaminase domain, bacterial tyrosyl-tRNA synthetases, and a number of uncharacterised, small proteins that may be involved in translation regulation []. The S4 domain probably mediates binding to RNA [].
Secretion of protein products occurs by a number of different pathways in bacteria. One of these pathways known as the type V pathway was first described for the IgA1 protease []. The protein component that mediates secretion through the outer membrane is contained within the secreted protein itself, hence the proteins secreted in this way are called autotransporters [, ]. This superfamily represents the pectate Lyase C-like domain found in autotransporters. This domain can also be found in phage P22 tail spike protein.
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 [].
Translins are DNA-binding proteins that specifically recognise consensus sequences at the breakpoint junctions in chromosomal translocations, mostly involving immunoglobulin (Ig)/T-cell receptor gene segments. They seem to recognise single-stranded DNA ends generated by staggered breaks occuring at recombination hot spots []. Translin folds into an α-α superhelix, consisting of two curved layers of alpha/alpha topology [, ].This entry also includes translin-associated protein X (TRAX), which was found to interact with translin [, ].
This family consists of the pleurocidin family of antimicrobial peptides. The first member identified in this family was Pleurocidin from the skin mucous secretions of the winter flounder (Pleuronectes americanus), peptides that exhibit antimicrobial activity against Gram-positive and Gram-negative bacteria [, ]. Pleurocidin is a 25-residue with an amphipathic α-helical conformation similar to other linear antimicrobial peptides and may play a role in innate host defence [, ].
This entry represents the RNA recognition motif 1 (RRM1) of polypyrimidine tract-binding protein homologue 3 (PTBPH3), also known as AtPTB3 in Arabidopsis.PTBPH3 shows significant sequence similarity to polypyrimidine tract binding protein (PTB), which is an important negative regulator of alternative splicing in mammalian cells. However, no major alternative splicing regulatory function of AtPTB3 was found []. Like PTB, PTBPH3 contains four RNA recognition motifs (RRM).
This entry represents the RNA recognition motif 2 (RRM2) of plant polypyrimidine tract-binding protein homologue 3 (PTBPH3), also known as AtPTB3 in Arabidopsis.PTBPH3 shows significant sequence similarity to polypyrimidine tract binding protein (PTB), which is an important negative regulator of alternative splicing in mammalian cells. However, no major alternative splicing regulatory function of AtPTB3 was found []. Like PTB, PTBPH3 contains four RNA recognition motifs (RRM).
This entry represents the RNA recognition motif 3 (RRM3) of plant polypyrimidine tract-binding protein homologue 3 (PTBPH3), also known as AtPTB3 in Arabidopsis.PTBPH3 shows significant sequence similarity to polypyrimidine tract binding protein (PTB), which is an important negative regulator of alternative splicing in mammalian cells. However, no major alternative splicing regulatory function of AtPTB3 was found []. Like PTB, PTBPH3 contains four RNA recognition motifs (RRM).
This family consists of the cytochrome c oxidase polypeptide 2A family. The ba3-type cytochrome c oxidase from Thermus thermophilus is known as a two subunit enzyme. From its crystal structure, it was discovered that an additional transmembrane helix, subunit IIa, spans the membrane. This subunit consists of 34 residues forming one helix across the membrane. The presence of this subunit seems to be important for the function of cytochrome c oxidases [].
G protein-coupled receptor 12 (GPR12) was initially isolated from a rat pituitary library, and is found in discrete regions of the brain, pituitary and testis, but is absent in other tissues [, ]. Three human homologues (GPR12, GPR6 and GPR3) have also been isolated []. The 3 genes have been localised to human chromosomal regions 13q12, 6q21and 1p34.3-p36.1 respectively.This entry represents G protein-coupled receptor 12. It is an orphaned receptor, with no endogenous ligand having yet been identified.
Cas1p protein of Cryptococcus neoformans is required for the synthesis of O-acetylated glucuronoxylomannans, a consitutent of the capsule, and is critical for its virulence []. The multi TM domain of the Cas1p was unified with the 10 TM Sugar Acyltransferase superfamily []. This superfamily is comprised of members from the OatA, MdoC, OpgC, NolL and GumG families in addition to the Cas1p family []. The Cas1p protein has a N-terminal PC-esterase domain with the opposing acyl esterase activity [].
G protein-coupled receptor 12 (GPR12) was initially isolated from a rat pituitary library, and is found in discrete regions of the brain, pituitary and testis, but is absent in other tissues [, ]. Three human homologues (GPR12, GPR6 and GPR3) have also been isolated []. The 3 genes have been localised to human chromosomal regions 13q12, 6q21and 1p34.3-p36.1 respectively.This entry represents the G protein-coupled receptor 3. It is an orphaned receptor, with no endogenous ligand having yet been identified.
G protein-coupled receptor 12 (GPR12) was initially isolated from a rat pituitary library, and is found in discrete regions of the brain, pituitary and testis, but is absent in other tissues [, ]. Three human homologues (GPR12, GPR6 and GPR3) have also been isolated []. The 3 genes have been localised to human chromosomal regions 13q12, 6q21and 1p34.3-p36.1 respectively.This entry represents G protein-coupled receptor 6, which is an orphaned receptor, no endogenous ligand having yet been identified.
Neprilysin (also known as MME, NEP or CD10) is a membrane metallo-endopeptidase acting on polypeptides of up to 30 amino acids. It degrades the amyloid β-peptide (Abeta) in the central nervous system, which is associated with Alzheimer's disease []. It was identified in leukemia as a tumour-specific antigen (common acute lymphoblastic leukemia antigen) and is used in cancer diagnosis []. It plays an important role in inflammatory responses []. In mammals, it is involved in mammary gland development [].
Serine/threonine kinase HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumours, but is not necessary for c-myc-induced primary tumour formation or normal development. It is required for HER2/neu-induced tumour formation and maintenance of the cells' tumourigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas []. HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity [].
This family consists of insecticidal peptides isolated from venom of spiders of Aptostichus schlingeri (Trap-door spider) and Calisoga sp. Nine insecticidal peptides were isolated from the venom of the A. schlinger spider and seven of these toxins cause flaccid paralysis to insect larvae within 10 min of injection. However, all nine peptides were lethal within 24 hours []. The structure of Aps III was solved and shown to be an atypical knottin peptide with four disulphide bridges [].
This domain may be a potential Haspin-related leucine-zipper. A leucine zipper was proposed to be present towards the C-terminal of human Haspin, (upstream of the current family) []; however, as this domain would appear to span several helices and be largely within a loop structure [], the actual zipper might be further downstream, and be represented by this entry, which is the very C-terminal part of the Schizosaccharomyces pombe sequence.
Members of this family are encoded within bacterial typeIII secretion gene clusters. Among all species with type III secretion, those with this protein are found among those that target animal rather than plant cells. The member of this family in Yersinia was shown by mutation to be required for type III secretion of Yops effector proteins and therefore is believed to be part of the secretion machinery [].
This entry represents the C-terminal domain of trans-2-enoyl-CoA reductase that binds to FAD. The activity was characterised in Euglena where an unusual fatty acid synthesis path-way in mitochondria performs a malonyl-CoA independent synthesis of fatty acids leading to accumulation of wax esters, which serve as the sink for electrons stemming from glycolytic ATP synthesis and pyruvate oxidation []. The full enzyme catalyses the reduction of enoyl-CoA to acyl-CoA.
The S4 domain is a small domain consisting of 60-65 amino acid residues that was detected in the bacterial ribosomal protein S4, eukaryotic ribosomal S9, two families of pseudouridine synthases, a novel family of predicted RNA methylases, a yeast protein containing a pseudouridine synthetase and a deaminase domain, bacterial tyrosyl-tRNA synthetases, and a number of uncharacterised, small proteins that may be involved in translation regulation []. The S4 domain probably mediates binding to RNA [].
Kinectin is a protein that binds kinesin and has a role in organelle motility []. Different isoforms exist that may be involved in intracellular motility in different cellular processes. As an integral transmembrane protein on the endoplasmic reticulum it is involved in endoplasmic reticulum extension. A smaller isoform was found to be associated with mitochondria, and its interaction with kinesin shown to influence mitochondrial dynamics [].
This domain superfamily was determined from the crystal structure of a protein of unknown function from Rhizobium meliloti (Sinorhizobium meliloti). The domain is found in a family, which consists of several short bacterial proteins of around 100 residues in length. The function of this domain is unknown. Structurally, this domain is multihelical, it is composed of intertwined homodimer where there are four core helices in each subunits.
Bone marrow stromal antigen 2, also known as tetherin, is an antiretroviral defence protein, that blocks release of enveloped virus from the cell surface [, , ]. Bst2/tetherin contains two membrane anchors which are employed to retain some enveloped viruses, including HIV-1, tethered to the plasma membrane in the absence of virus encoded antagonists []. Its expression is induced by interferon-alpha []and was originally linked to B cell development [].
Mucin-20 (MUC20) was identifiied as a gene that is up-regulated in the renal tissues of patients with immunoglobulin A nephropathy []. It is a regulator of the Met signaling cascade. MUC20 associates with Met which is the hepatocyte growth factor (HGF) receptor, and has a role in suppressing the Grb2-Ras pathway. Production of MUC20 reduced HGF-induced matrix metalloproteinase expression and proliferation, which require the Grb2-Ras pathway [].
This family consists of several bacterial and eukaryotic Aegerolysin-like proteins. Aegerolysin and ostreolysin are expressed during formation of primordia and fruiting bodies, and these haemolysins may play an important role in initial phase of fungal fruiting. The bacterial members of this family are expressed during sporulation []. Ostreolysin was found cytolytic to various erythrocytes and tumour cells []. It forms transmembrane pores 4 nm in diameter. Its activity is inhibited by total membrane lipids, and modulated by lysophosphatides.
This domain can be found in yeast peroxisomal proteins, such as PEX28-32 family members. This domain can also be found in animal TECPR1 family members. Peroxisomes play diverse roles in the cell, compartmentalising many activities related to lipid metabolism and functioning in the decomposition of toxic hydrogen peroxide. Sequence similarity was identified between two hypothetical proteins and the peroxin integral membrane protein Pex24p [].In humans, TECPR1 is a tethering factor involved in autophagy [].
Macrophage-capping protein (CapG) belongs to the Villin/Gelsolin family, whose members are Ca(2+)-dependent, multidomain regulators of the actin cytoskeleton []. CapG was first isolated from alveolar macrophages as an actin-modulating protein that reversibly cap the barbed ends of actin filaments []. Unlike most of the Villin/Gelsolin family members, it does not sever actin filaments []. It is involved in cell invasion and metastasis in several cancers [, ].
The structure model of this domain folds into 10 β-strands arranged in two β-sheets as well as 4-5 elongated α-helices. The β-sheets distantly resemble the Collagen_bind () domain. It is annotated N-terminal to repeating stalk domains in bacterial surface proteins. This domain can be found on a E. faecalis protein encoded by the EF3314 gene, which was proposed to contribute to the interaction of E. faecalis with the host and to the bacterial virulence [].
This family represents a subfamily of a C-N bond-cleaving hydrolases (see ). Members occur as part of a cluster of genes in a probable biosynthetic cluster that contains a radical SAM protein, an N-acetyltransferase, a flavoprotein, several proteins of unknown function, and usually a glycosyltransferase. Members are closely related to a characterised aliphatic nitrilase from Rhodopseudomonas rhodochrous J1, for which an active site Cys was found at position 165. Members of this family are uncharacterised.
This family consists of several invasion associated locus B (IalB) proteins and related sequences. IalB is known to be a major virulence factor in Bartonella bacilliformis where it was shown to have a direct role in human erythrocyte parasitism. IalB is up-regulated in response to environmental cues signalling vector-to-host transmission. Such environmental cues would include, but not be limited to, temperature, pH, oxidative stress, and haemin limitation. It is also thought that IalB would aide B. bacilliformis survival under stress-inducing environmental conditions [].
This entry represents a conserved region situated towards the C-terminal end of IcmF-like proteins. IcmF was thought to be involved in Vibrio cholerae cell surface reorganisation that results in increased adherence to epithelial cells leading to an increased conjugation frequency []. IcmF as a whole interacts with DotU whereby these bind tightly and form the docking area of the T6SS within the inner membrane. The exact function of this domain is not clear [].
Stonin 2 is involved in clathrin mediated endocytosis []. It binds to Eps15 by its highly conserved NPF motif. The complex formed has been shown to directly associate with the clathrin adaptor complex AP-2, and to localize to clathrin-coated pits (CCPs) []. In addition, stonin2 was recently identified as a specific sorting adaptor for synaptotagmin, and may thus regulate synaptic vesicle recycling []. This entry represents the N-terminal domain of stonin-2. It is found in association with .
DivIC was identified as a gene required for vegetative and sporulation septum formation in Bacillus subtilis []. DivIC forms a trimeric complex with another two proteins that are essential for cell division, DivIB and FtsL. The trimeric complex localizes at the septum and is regulated during the cell cycle through controlled formation of the DivIC/FtsL heterodimer []. DivIC seems to stabilizes FtsL against RasP cleavage [].
Protein SSX1 can repress transcription, and this has been attributed to a putative Kruppel associated box (KRAB) repression domain at the N terminus. However, from the analysis of these deletion constructs further repression activity was found at the C terminus of SSX1. Which has been called the SSXRD (SSX Repression Domain). The potent repression exerted by full-length SSX1 appears to localise to this region [].
This is a family of unknown function found in Alphabaculovirus. It includes the ECORI-T site protein ETS, which was identified as a 1.7-kb transcript from the coding region within the EcoRI T fragment (29.0 to 30.1 map units) in Autographa californica nuclear polyhedrosis virus (AcMNPV) []. This protein is produced as an early stage transcript and persists throughout infection, although its function is unknown [].
Interleukins (IL) are a group of cytokines that play an important role in the immune system. They modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells. This entry represents interleukin-34 (IL-34), it was identified via functional screening of a library of secreted proteins []. This cytokine promotes the differentiation and viability of monocytes and macrophages through the colony-stimulating factor-1 receptor (CSF1R) [].
This family of archaeal and bacterial proteins is homologous to the eukaryotic translation intiation factor SUI1 involved in directing the ribosome to the proper start site of translation by functioning in concert with eIF-2 and the initiator tRNA-Met. The function of non-eukaryotic family members is unclear. Escherichia coli YciH is a non-essential protein and was reported to be able to perform some of the functions of IF3 in prokaryotic initiation [, ].
OpcA protein may play a role in the functional assembly of glucose-6-phosphate dehydrogenase []. The opcA gene is found immediately downstream of zwf, the glucose-6-phosphate dehydrogenase (G6PDH) gene, in a number of species, including Mycobacterium tuberculosis, Streptomyces coelicolor, Nostoc punctiforme (strain ATCC 29133/PCC 73102), and Synechococcus sp. (strain PCC 7942). In the latter, disruption of opcA was shown to block assembly of G6PDH into active oligomeric forms.This entry represents the C-terminal domain.
OpcA protein may play a role in the functional assembly of glucose-6-phosphate dehydrogenase []. The opcA gene is found immediately downstream of zwf, the glucose-6-phosphate dehydrogenase (G6PDH) gene, in a number of species, including Mycobacterium tuberculosis, Streptomyces coelicolor, Nostoc punctiforme (strain ATCC 29133/PCC 73102), and Synechococcus sp. (strain PCC 7942). In the latter, disruption of opcA was shown to block assembly of G6PDH into active oligomeric forms.This entry represents the N-terminal Rossmann-like domain.
This entry represents the bacterial phosphate-selective porins O and P. These are anion-specific porins, the binding sites of which has a higher affinity for phosphate than chloride ions. Porin O has a higher affinity for polyphosphates, while porin P has a higher affinity for orthophosphate []. In Pseudomonas aeruginosa, porin O was found to be expressed only under phosphate-starvation conditions during the stationary growth phase [].
The YneA protein is responsible for cell division suppression during the SOS response in Bacillus subtilis. Localization of the FtsZ protein to the cell division site was reduced in dinR-disrupted or yneA-expressing cells, further suggesting that the YneA protein suppresses cell division through the suppression of FtsZ ring formation. Interestingly, the B. subtilis YneA protein is structurally and phylogenetically unrelated to its functional counterpart in Escherichia coli, SulA [](see ).
This entry represents a group of thiol:disulfide interchange proteins, including TxlA from Cyanobacteria and HCF164 from Arabidopsis. HCF164 is a membrane-anchored thioredoxin-like protein that acts as a transducer of reducing equivalents in the thylakoid lumen. It contains a membrane-spanning sequence and a thioredoxin-like CXXC motif in the N- and C-terminal regions, respectively. The hcf164 mutant was found to be impaired in the stable assembly of the cytochrome b6 f complex within thylakoid membrane [].
Members of this family are VapC proteins that consist almost entirely of a PIN (PilT N terminus) domain. This family was originally defined a set of twelve closely related paralogs found in Mycobacterium tuberculosis, but additional members are found now Synechococcus sp. WH8102, etc. This family includes ribonucleases VapC24 and Vap25 among others. They are the toxic component of a toxin-antitoxin (TA) module. They act as an RNase and all their toxic effects are neutralised by coexpression with cognate antitoxin [].
The hD52 gene was originally identified through its elevated expression level in human breast carcinoma. Cloning of D52 homologues from other species has indicated that D52 may play roles in calcium-mediated signal transduction and cell proliferation. Two human homologues of hD52, hD53 and hD54, have also been identified, demonstrating the existence of a novel gene/protein family []. These proteins have an N-terminal coiled-coil that allows members to form homo- and heterodimers with each other [].
is a subunit of the terminal quinol oxidase present in the plasma membrane of Acidianus ambivalens, with calculated molecular mass of 20.4kDa []. Thiosulphate:quinone oxidoreductase (TQO) is one of the early steps in elemental sulphur oxidation. A novel TQO enzyme was purified from the thermo-acidophilic archaeon A. ambivalens and shown to consist of a large subunit (DoxD) and a smaller subunit (DoxA). The DoxD- and DoxA-like two subunits are fused together in a single polypeptide in .
This family of plant transcription factors includes GLABROUS1 enhancer-binding protein (GeBP) and GeBP-like proteins, and storekeeper and storekeeper-like (STKL) transcription factors.GeBP and GeBP-like proteins play a redundant role in cytokinin hormone pathway regulation []. Storekeeper was identified as a B-box motif binding factor that regulates expression of patatin, a storage protein in potato []. Storekeeper-like transcription factors STKL1 and STKL2 function as transcription factors in the glucose signaling pathway [].
This entry represents a group of plant PX domain-containing proteins, including EREX and EREL1/2 from Arabidopsis. EREX interacts with ARA7 and RHA1 (RAB5 members), whereas EREL1/2 was not shown to interact with these RAB5 members. EREX serves as an effector of canonical RAB5 GTPases and regulates membrane trafficking to protein storage vacuole. EREX and EREL1 act in the same trafficking and developmental events, while EREL2 has a partially redundant function with EREX and EREL1 [].
This repeat contains a highly conserved, characteristic sequence motif, KGG, that is recognised by plants and lower eukaryotes.Further downstream from this motif is a Walker A, nucleotide binding motif. YciG is expressed as part of a three-gene operon, yciGFE and this operon is induced by stress and is regulated by RpoS, which controls the general stress-response in E coli. YciG was shown to be important for stationary-phase resistance to thermal stress and in particular to acid stress [].
In E.coli four ABC-F proteins have been characterised: EttA, YbiT, YheS, and Uup. EttA was shown to interact with the ribosome (). YbiT, YheS, and Uup have also been shown to bind to the ribosome [].This domain is an extension of some members of and other ABC-transporter families. It is not responsible for ribosome binding, but it is used by proteins which bind to the ribosome to stabilise the interaction.
This entry represents a conserved linker between the second and the third RRM domain in human RBM39 (also known as CAPER) protein and other RNA splicing proteins. CAPER is a transcriptional coactivator of activating protein-1 (AP-1) and estrogen receptors (ERs). This linker was implicated in interactions with ERalpha and ERbeta []. Preliminary results from JCSG suggest that this is a structured domain with a well defined fold.
Following a subtractive bioinformatics analysis of cattle placenta ESTs, a number of novel transcripts were identified. Gene-expression profiles and further bioinformatics analyses have indicated that the identified genes may be of evolutionary and physiological importance, with possible roles in placental adaptation []. Revealed by this study was so-called Cattle Cerebrum and Skeletal Muscle-Specific Transcript 1 (CCSMST1) [], whose translation product is believed to contain a signal peptide and a single transmembrane (TM) domain [].
This bifunctional enzyme catalyses the condensation of formaldehyde with tetrahydromethanopterin (H4MPT) to 5,10-methylenetetrahydromethanopterin and the formation of ribulose-5-phosphate and formaldehyde from 3-hexulose-6-phosphate. Formaldehyde activating enzyme (Fae) was first discovered in methylotrophic bacteria, where it is involved in the oxidation of methanol to CO2 and in formaldehyde detoxification. The genome of Methanosarcina barkeri contains both the faeA gene as well as a second gene, faeB-hpsB, which is shown to code for a 42kDa protein with both Fae activity and hexulose-6-phosphate synthase (Hps) activity [].
Members of this family include the largely uncharacterised BrkB (Bordetella resist killing by serum B) from Bordetella pertussis. It is essential for resistance to complement-dependent killing by serum in Bordetella pertussis []. Some members have an additional C-terminal domain. Paralogs from E. coli (yhjD) and Mycobactrium tuberculosis (Rv3335c) are part of a smaller, related subfamily that form their own cluster []. This family was originally predicted to be ribonuclease BN []but this prediction has since been shown to be incorrect [].
Melanoma-associated antigen 1 (MAGE1 or MAGEA1) belongs to a family of genes that are active in various types of tumours and silent in normal tissues except in male germ-line cells [, ]. MAGEA1 can act as a transcriptional repressor by binding to the transcriptional regulator SKIP (Ski Interacting Protein). MAGEA1 was also found to actively repress transcription by binding and recruiting histone deacetylase 1 (HDAC1). It could therefore contribute to specific gene expression patterns driving tumour cell growth or spermatogenesis [].
The melanoma antigen (MAGE) protein family contains more than 25 members that share a conserved MAGE homology domain (MHD). Some MAGE antigens constitute important targets for antitumor immunotherapy. MAGED4 was originally identified as a glioma-specific antigen. It is predominantly expressed in glioma, but not in normal tissues except brain and ovary [, ]. MAGED4 contributes to proliferation, migration, and invasion of tumor cells in different types of cancer [, , ].
This entry represents the C-terminal domain of the neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 1 (NYAP1). NYAP1 belongs to the neuronal tyrosine-phosphorylated adaptor for the PI 3-kinase (NYAP) family, which consists of NYAP1, NYAP2, NAP3/Myosin16. NYAPs activate PI3K in PI3K pathway, which is a fundamental pathway for various cellular events in neurons. They also interact with components of the WAVE1 complex, which mediates actin cytoskeleton remodeling through Arp2/3 complex. It was suggested that NYAPs connect PI3K activation to WAVE1 signalling in neurons [].
This entry represents serine/threonine-protein kinases () such as Rio1. RIO kinases are atypical members of the protein kinase family that are required for ribosome biogenesis and cell cycle progression []. Rio1 is present in all organisms from archaea to mammals, and was shown to be absolutely essential in Saccharomyces cerevisiae (Baker's yeast) for the processing of 18S ribosomal RNA, as well as for proper cell cycle progression and chromosome maintenance [].
Nucling, also known as uveal autoantigen with coiled-coil domains and ankyrin repeats (UACA), is a proapoptotic protein that regulates the apoptosome and nuclear factor-kappa B (NF-kappaB) signalling pathways []. It was first identified in murine embryonal carcinoma cells []. It is associated with the apoptosome pathway by inducing translocation of Apaf-1 from the cytoplasm into the nucleus following cytotoxic stress []. It also mediates apoptosis by inhibiting expression of galectin-3 [].
The ScdA protein was originally identified as a cell wall biosynthesis protein since mutations in the scdA gene produce cell walls with highly aberrant morphology []. Subsequent studies have shown that ScdA belongs to the wider Repairs of iron centres (RIC) family and is a di-iron protein that, amongst other functions, protects the cell from damage caused by exposure to nitric oxide and to hydrogen peroxide [, ].
SAT2 (also known as spermidine/spermine-N1-acetyltransferase-2, SSAT2) was originally identified based on homology to SSAT1, a protein involved in polyamine catabolism. However, SSAT2 does not acelylate polyamines, but instead acetylates thialysine, a structural analogue of L-lysine []. The role of SSAT2 is still unclear []. It can function as a transcriptional coactivator for NF-kappaB []. It seems to be an essential component of the ubiquitin ligase complex that regulates hypoxia-inducible factor 1alpha [].
This domain was first identified in drosophila MSL1 (male-specific lethal 1) []. In drosophila it binds to the histone acetyltransferase males-absent on the first protein (MOF) and to protein male-specific lethal-3 (MSL3) [, ]. This domain can also be found in KAT8 regulatory NSL complex subunit 1 (KANSL1 or NSL1), which is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription [].
The exact function of this protein is unknown, but likely is linked to methanogenesis or a process closely connected to it. A 69-amino acid core region of this 110-amino acid domain contains eight invariant Cys residues, including two copies of a motif [WFY]CCxxKPC. These motifs could be consistent with predicted metal-binding transcription factor as was suggested for the family. Some members of this family have an additional N-terminal domain of about 250 amino acids from the nifR3 family of predicted TIM-barrel proteins.
Junctional adhesion molecule 2 (JAM2), also known as VE-JAM or JAM-B, is a type I integral membrane protein that contains two Ig-like folds and three N-linked glycosylation sites in the extracellular domain []. JAM2 was initially identified as an endothelial adhesion molecule that plays a role in the architecture of interendothelial junctions and control leukocyte migration to inflammatory sites []. JAM2 interacts with T, NK, and dendritic cells through JAM3 [].
This entry includes Rho guanine nucleotide exchange factors 10 and 17.ARHGEF10 is a Rho guanine nucleotide exchange factor that may play a role in developmental myelination of peripheral nerves []. It was found to regulate mitotic spindle formation and play a role in the regulation of the cell division cycle [].ARHGEF17 is a guanine nucleotide exchange for for RhoA GTPases; it contains a Dbl homology (DH) domain but lacks the typical pleckstrin homology domain [].
Members of this protein family represent a distinct clade among the larger set of proteins that belong to . Proteins from this clade are found in genome sequence if and only if the species sequenced is one of the methanogens. All methanogens belong to the archaea; some but not all of those sequenced are hyperthermophiles. This protein family was detected by the method of partial phylogenetic profiling [].
This entry includes a set of Actinobacterial proteins, including Rv2632c from Mycobacterium tuberculosis that is strongly implicated in the onset of non-replicating persistence, and thereby latent tuberculosis. Rv2632c contains a dsRBD-like (2 layers alpha/beta) fold (PDBe:2fgg). It shares remarkable similarity with bacterial hibernation factors, despite very low sequence similarity. Based on this structure it was predicted that Rv1738, highly up-regulated in conditions that mimic the onset of persistence, helps trigger dormancy by association with the bacterial ribosome [].
Members of this protein family are about 265 residues long and each contains an S4 RNA-binding domain of about 48 residues. The member from the Cyanobacterium, Synechocystis sp. (strain PCC 6803), was detected as a novel polypeptide in a highly purified preparation of active photosystem II []. The phylogenetic distribution, including Cyanobacteria and Arabidopsis, supports a role in photosystem II, although the high bit score cut-off for this model excludes similar sequences in non-photosynthetic organisms such as Carboxydothermus hydrogenoformans, a Gram-positive bacterium.
This entry contains proteins that have the C-terminal domain of a family of multiple membrane-spanning proteins of Gram-positive bacteria. One member was shown to be a host protein essential for phage infection, so many members of this family are called "phage infection protein". A separate model, , represents the conserved N-terminal domain. The domains are separated by regions highly variable in both length and sequence, often containing extended heptad repeats as described in .
This entry represents the N-terminal domain of a family of multiple membrane-spanning proteins from Gram-positive bacteria. One member was shown to be a host protein essential for phage infection, so many members of this family are called "phage infection protein". A separate entry, , represents the conserved C-terminal domain. The domains are separated by regions highly variable in both length and sequence, often containing extended heptad repeats as described in .
Syntenin-1 was originally identified as a syndecan-binding PDZ protein []. Later, Syntenin-1 is found to be a scaffolding protein that interacts with several membrane receptors, such as the lymphocyte receptor CD6 and the interleukin 5 (IL-5) receptor [, , ]. It has diverse cellular roles including trafficking of transmembrane proteins, neuro and immunomodulation, exosome biogenesis, and tumorigenesis [, , , ]. Its structure has been solved [, ].
This entry includes Cep85 and Cep85L from animals.Cep85 is a centrosomal protein of 85kDa []. It is a centriole duplication factor that directly interacts with STIL. It is essential for efficient centriolar targeting of STIL, PLK4 activation and faithful daughter centriole assembly [].Centrosomal protein of 85kDa-like (CEP85L) may localise to the centrosome []. It is also known as breast cancer antigen NY-BR-15 []. A chromosomal aberration involving CEP85L was found in a patient with T-lymphoblastic lymphoma and associated myeloproliferative neoplasm [].
Phosphotransferase RcsD is a component of the Rcs signaling system. RcsD is a phosphotransfer intermediate between the sensor kinase RcsC and 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 [, , ].
SE-cephalotoxin was reported in the salivary gland of the cuttlefish Sepia esculenta. Cephalopods contain toxins in their salivary glands, which may help to paralyze prey animals. This protein seems to be conserved in bonyfishes; it has been found in the swim bladder of the European Eel [].This entry also includes protein rapunzel, whose function is still not clear. Mutations of the rapunzel gene cause skeletal overgrowth in Zebrafish [].
This small protein has a very limited distribution, being found so far only among some gamma-Proteobacteria. The member from Escherichia coli was shown to bind selenium in the absence of a working SelD-dependent selenium incorporation system []. Note that while the E. coli member contains a single Cys residue, a likely selenium binding site, some other members of this protein family contain two Cys residues or none.
This family consists of the karyopherins importin-beta and transportin. Importin subunit beta-1 forms a complex with an importin alpha subunit. The importin complex is required for nuclear protein import. Importins bind to NLSs in their protein cargos to transport them through the nuclear pore into the nucleus [].Transportin-1 and -2 also function in nuclear import []. Transportin-1 was first identified as the import factor for the heterogeneous ribonucleoprotein A1 (hnRNP A1) [].
Suppressor of white apricot, also known as SWAP, is an alternative splicing regulator. SWAP was originally identified in Drosophila as a suppressor of the transposon-induced white-apricot mutation. It regulates splicing of several genes, including Swap itself []. Human SWAP has been shown to regulate alternative mRNA splicing of CD45 exon 4 and fibronectin IIICS [].This entry also includes CLK4-associating serine/arginine rich protein (CLASRP, also known as SWAP2). The function of SWAP2 is not clear.
Trichome birefringence-like (TBL) proteins are proposed to encode wall poly-saccharide specific O-acetyltransferases based on the existing data for some members of the TBL family: altered xyloglucan 4 (AXY4/TBL270) and altered xyloglucan 4-like (AXY4L/TBL22), two xyloglucan specific O-acetyltransferases in non-seed tissues and seeds, respectively [, ].This entry includes TBR (Trichome birefringence) and TBL4 from Arabidopsis. TBR is the original gene after which this family was named. The tbr-mutant exhibits a defect in cellulose crystallinity in its trichomes and shows alterations in pectin esterification [].
This entry represents a group of plant auxin-responsive proteins, known as small auxin-up RNA (SAUR) []. The first SAUR gene was originally identified in soybean hypocotyls []. SAUR genes are mainly expressed in growing hypocotyls or other elongating tissues, implying that they play a role in the regulation of cell elongation []. SAUR proteins may provide a mechanistic link between auxin and plasma membrane H+-ATPases (PM H+-ATPases) in Arabidopsis thaliana [].
The first member of the FEZ (fasciculation and elongation protein zeta) family identified was unc-76, from C. elegans. The protein is necessary for normal axon fasciculation and is required for axon-axon interactions []. Later, two human homologues, FEZ1 and FEZ2, were identified []. FEZ1 and FEZ2 interact with PKCzeta and have been shown to induce neurite extension of PC12 cells when co-expressed with a constitutively active mutant of PKCzeta [].
Diedel (die) was identified as an insect immune response protein. It is up-regulated after a septic injury and may act as a negative regulator of the JAK/STAT signalling pathway []. Its homologues can be found in Drosophila and Acyrtosiphon pisum. Interestingly, the orthologues of the die gene are present in the genome of insect DNA viruses of the Baculoviridae and Ascoviridae families. The viral homologues suppress the immune deficiency (IMD) pathway in Drosophila [].
This is a helical domain found in NLRC4, an nucleotide-binding and oligomerization domain-like receptor (NLR) protein. Structural and functional studies indicate that the helical domain HD2 repressively contacted a conserved and functionally important α-helix of the NBD (nucleotide binding domain) in NLRC4. Furthermore, the HD2 domain was shown to cap the N-terminal side of the LRR (leucine-rich repeat) domain via extensive interactions []. Other proteins carrying this domain include baculoviral IAP repeat-containing protein 1 (Birc1), also known as neuronal apoptosis inhibitory protein (Naip).
This is a family of small, highly hydrophobic proteins. Over-expression of this protein in Escherichia coli is associated with bacitracin resistance [], and the protein was originally proposed to be an undecaprenol kinase called bacA. BacA protein, however, does not show undecaprenol phosphokinase activity []. It is now known to be an undecaprenyl pyrophosphate phosphatase () and is renamed UppP. It is not the only protein associated with bacitracin resistance [, ].
L-fucose isomerase () converts the aldose L-fucose into the corresponding ketose L-fuculose during the first step in fucosemetabolism using Mn2+ as a cofactor. The enzyme is a hexamer, forming the largest structurally known ketol isomerase, and has no sequence or structural similarity with other ketol isomerases. The structure was determined by X-ray crystallography at 2.5 A resolution []. This entry represents the C-terminal domain of L-fucose isomerase.
The ODP (Oxygen-binding Di-iron Protein) domain containing proteins belong to a subfamily of the metallo-beta-lactamase superfamily recruited to various bacterial and archaeal signal transduction pathways, including chemotaxis, to function as oxygen and iron sensors. ODP was shown to act as a sensor for chemotactic responses to both iron and oxygen in the human pathogen Treponema denticola (Td). The ODP di-iron site binds oxygen at high affinity to reversibly form an unusually stable peroxo adduct [].
Structural analysis revealed that the catalytic domain of LytB consists of three structurally independent modules: SH3b, WW domain-like, and the glycoside hydrolase family 73 (GH73). This entry is the WW like domain found in endo-beta-N-acetylglucosaminidase LytB from Streptococcus pneumoniae. Functional analysis show that the deletion of both SH3b and WW modules almost completely abolished the activity of LytB. Furthermore, it was shown that the SH3b and WW modules are indispensable for LytB in cell separation [].
This entry represents the third SH3 domain, located in the middle, of SH3RF3.SH3RF3 (also known as POSH2) is a scaffold protein with E3 ubiquitin-protein ligase activity []. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating JNK mediated apoptosis in certain conditions []. It also interacts with GTP-loaded Rac1 []. SH3RF3 is highly homologous to SH3RF1; it also contains an N-terminal RING finger domain and four SH3 domains.
SASH3, also called SLY/SLY1 (SH3-domain containing protein expressed in lymphocytes), is expressed exclusively in lymhocytes and is essential in the full activation of adaptive immunity []. It is involved in the signaling of T cell receptors []. It was the first described member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) and SH3 domains [].This entry represents the SH3 domain of SASH3.
This entry contains rhamnose mutarotase from Escherichia coli, previously designated YiiL as an uncharacterised protein, and close homologues associated with rhamnose dissimilation operons in other bacterial genomes. Mutarotase is a term for an epimerase that changes optical activity. This enzyme was shown experimentally to interconvert alpha and beta stereoisomers of the pyranose form of L-rhamnose []. The crystal structure of this small (104 amino acid) protein shows a locally asymmetric dimer with active site residues of His, Tyr, and Trp [].
RACK7 (also called human protein kinase C-binding protein) was identified as a potential tumour suppressor gene. It shares domain architecture with BS69/ZMYND11; both have been implicated in the regulation of cellular proliferation []. RACK7 functions together with KDM5C as an enhancer 'brake' to ensure appropriate enhancer activity [].This entry represents the bromodomain of RACK7. Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine [].
The human protein polybromo-1 (PBRM1, also known as BAF180) is part of a SWI/SNF chromatin-remodeling complex []. It was shown that polybromo bromodomains bind to histone H3 at specific acetyl-lysine positions. Bromodomains are found in many chromatin-associated proteins and in nuclear histone acetyltransferases. They interact specifically with acetylated lysine, but not all the bromodomains in polybromo may bind to acetyl-lysine [, ]. Polybromo contains 6 bromodomains. This entry represents the fifth one (BD5). Mutations in BD5 moderately affect PBRM1 chromatin association [].
pNO40 (also known as Zinc finger CCHC domain-containing protein 17) is a nucleolar protein of unknown function with an N-terminal S1 RNA binding domain, a CCHC type zinc finger, and clusters of basic amino acids representing a potential nucleolar targeting signal. pNO40 was identified through a yeast two-hybrid interaction screen of a human kidney cDNA library using the pinin (pnn) protein as bait. pNO40 is thought to play a role in ribosome maturation and/or biogenesis [].
1-(5-phosphoribosyl)-5-[(5-phosphoribosylamino)methylideneamino]imidazole-4-carboxamide isomerase (), also known as Phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase or HisA, catalyses the fourth step in histidine biosynthesis. HisA from Lactococcus lactis was found to be inactive []. The putative HisA from Thermotoga maritima, is a conspicuous outlier to the set of all other HisA, including experimental HisA from the bacterium Escherichia coli and the Archaeaon Methanococcus voltae. Neighbour joining shows HisA from Thermotoga maritima to be within the HisA family (with HisF as an outgroup) but with a long branch.
Alanine racemase () plays a role in providing the D-alanine required for cell wall biosynthesis by isomerising L-alanine to D-alanine.The molecular structure of alanine racemase from Bacillus stearothermophilus (Geobacillus stearothermophilus) was determined by X-ray crystallography to a resolution of 1.9 A []. The alanine racemase monomer is composed of two domains, an eight-stranded alpha/beta barrel at the N terminus, and a C-terminal domain essentially composed of β-strand. This entry represents the C-terminal domain.
The NarG-like domain was originally characterised in the molybdo-bis(molybdopterin guanine dinucleotide) (Mo-bisMGD) cofactor-binding subunit NarG from nitrate reductase subunit. It is also found in homologous subunits from other oxidorectuases such as the coenzymeB--coenzymeM heterodisulphide reductase subunit E. Structurally this domain is composed of four α-β subdomains that are organised around the catalytic centre of the enzyme complex []. Subdomains II and III are organised around the Mo-bisMGD cofactor.
