This entry includes NFU1-like proteins from eukaryotes and some uncharacterised proteins from prokaryotes.Nfu functions as a scaffold protein for assembly and delivery of rudimentary Fe-S clusters to target proteins [, ]. A human Nfu homologue, HIRA-interacting protein 5 (HIRIP5), was first identified in a two-hybrid screen for proteins that interact with the transcription regulator HIRA []. It seems that two human Nfu isoforms are generated by alternative explicing, which are subsequently targeted to different subcellular compartments [].
E3 ubiquitin-protein ligase MSL2 (MSL2; [intenz:6.3.2.-]) is an E3 ubiquitin ligase that promotes monoubiquitination of histone H2B at 'Lys-35' (H2BK34Ub), but not that of H2A. It is a component of MSL complex [].The male-specific lethal (MSL) complex is a histone acetyltransferase with specificity for histone H4 'lysine-16' in chromatin. The complex consists of MOF, MSL1, MSL2, and MSL3 []. The complex was first identified in Drosophila.
Male-specific lethal 3 homolog (MSL3) is a component of the MSL complex []. MSL3 has a chromodomain by which it interacts with DNA [, ]and an MRG domain with which it interacts with MSL1 [].The male-specific lethal (MSL) complex is a histone acetyltransferase with specificity for histone H4 'lysine-16' in chromatin. The complex consists of MOF, MSL1, MSL2, and MSL3 []. The complex was first identified in Drosophila.
Nuclear distribution gene C homologue (nudC) proteins form complexes with other nud proteins and are involved in several cellular division activities. Recently it was shown that nudC regulates platelet-activating factor (PAF) acetylhydrolase with PAF being a pro-inflammatory secondary lipidic messenger []. The N terminus of nudC proteins contain a highly conserved region consisting of a predicted three helix bundle. This entry represents the N-terminal conserved domain.
This group of enzymes was suggested to be related to the MinD family of ATPases involved in regulation of cell division in bacteria and archaea []. Further sequence analysis suggests a model for the interaction of CobB and CobQ with their respective substrates []. CobB and CobQ were also found to contain unusual Triad family (class I) glutamine amidotransferase domains with conserved Cys and His residues, but lacking the Glu residue of the catalytic triad [].
This entry represents the C-terminal region of the iron-sulphur protein LdpA (Light dependent period), which is found in phototropic organisms. LdpA was originally identified in cyanobacteria where it is involved in light-dependent modulation of the circadian clock. The presence of iron-sulphur clusters on LdpA suggests that it may modulate the circadian clock as an indirect function of light intensity by sensing changes in cellular physiology [].
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 [].
Eukaryotic and prokaryotic molybdoenzymes require a molybdopterin cofactor(MoCF) for their activity. The biosynthesis of this cofactor involves acomplex multistep enzymatic pathway. One of the eukaryotic proteins involvedin this pathway is the Drosophila protein cinnamon []which is highly similar to gephyrin, a rat microtubule-associated protein which was thought to anchor the glycine receptor to subsynaptic microtubules.Cinnamon and gephyrin are evolutionary related, in their N-terminal half, to the Escherichia coli MoCF biosynthesis proteins mog/chlG and moaB/chlA2.
Thy-1 membrane glycoprotein (also known as CD90) was identified as an activation-associated cell adhesion molecule on human dermal microvascular endothelial cells. Its cellular effects vary; however, it most often seems to affect cell-cell or cell-matrix interactions and cellular adhesion and migration [, ]. Thy-1 interacts with the leukocyte integrin Mac-1 and may play an important role in the regulation of leukocyte recruitment to sites of inflammation []. It also plays an important role in normal retinal development [].
Peter Pan (PPAN) was initially identified in Drosophila melanogaster. PPAN is highly conserved and essential for maintaining growth and survival []. Human PPAN localizes to nucleoli and to mitochondria. It can shuttle between the nucleus and the cytoplasm in response to nucleolar stress and apoptosis induction []. PPAN knockdown has been linked to mitochondrial damage and stimulates autophagy []. The yeast homologues of PPAN, Ssf1 and Ssf2, are nucleolar ribosome biogenesis factors required for maturation of the large ribosomal subunit [].
This family contains lipoproteins from the Lyme disease spirochete Borrelia burgdorferi and related bacteria, including proteins from Paralogous family 54 (PFam54) and 60 (PFam60). The first crystal structure of B. burgdorferi PFam54 member BBA68 revealed a previously unseen novel fold, which, according to the CATH protein domain classification, was named the Bbcrasp-1 fold because of the common name used for the protein BBA68 [, ].
MASE4 (Membrane-Associated SEnsor) is an integral membrane sensor domain found in various GGDEF domain proteins, including a functional diguanylate cyclase DgcT (YcdT) and the enzymatically inactive CdgI (YeaI) of Escherichia coli []. In the Shiga toxin-producing enteroaggregative E. coli O104:H4, which caused the outbreak of the haemolytic uraemic syndrome in Germany in 2011, MASE4-containing diguanylate cyclase DgcX () was highly expressed, ensuring strong biofilm formation [].
EMSY was originally reported as a transcriptional repressor and breast cancer-associated protein that interacts with the BRCA2 protein []. It contains an N-terminal ENT domain which can bind BRCA2. It is involved in DNA damage repair, genomic instability, and chromatin remodeling []. EMSY can function as an integral component of an NIF-1 complex and play an important role in the regulation of nuclear receptor-mediated transcription []. It is also part of the EMSY/KDM5A/SIN3B complex that may function as a transcriptional repressor [].
This family includes SRP-independent targeting protein 2 (SND2) from yeast and transmembrane protein 208 (TMEM208) from mammals. Both are localized to the endoplasmic reticulum (ER) [, ]. SND2 works together with SND1 and SND3 in an alternative targeting route to the ER []. TMEM208 regulates both ER stress and autophagy [].SND2 was previously known as Env10 in Saccharomyces cerevisiae, and its homologue as Mug69 in Schizosaccharomyces pombe. They were identified as proteins involved in vacuolar processing and morphology []and meiosis [], respectively.
This family includes the Septation protein Etd1 from Schizosaccharomyces pombe, which activates the GTPase Spg1 to trigger signaling through the septum initiation network (SIN) pathway and onset of cytokinesis. The proper regulation of Etd1 is crucial for both activation of Spg1 in anaphase and inactivation of Spg1 when cytokinesis is complete []. It was suggested that Etd1 is the functional homologue of budding yeast Lte1 as they have the same function but a very low sequence similarity [].
This family consists of several mammalian microfibril-associated glycoprotein (MAGP) 1 and 2 proteins. MAGP1 and 2 are components of elastic fibres. MAGP-1 has been proposed to bind a C-terminal region of tropoelastin, the soluble precursor of elastin. MAGP-2 was found to interact with fibrillin-1 and -2, as well as fibulin-1, another component of elastic fibres. This suggests that MAGP-2 may be important in the assembly of microfibrils [].
Phospholipase B (PLB) catalyses the hydrolytic cleavage of both acylester bonds of glycerophospholipids. This family of PLB enzymes has been identified in mammals, flies and nematodes but not in yeast [, ]. In Drosophila this protein was named LAMA for laminin ancestor since it is expressed in the neuronal and glial precursors that surround the lamina [].This superfamily represents the domain 2 of phospholipase B. Structurally, this domain consists of 4 alpha helices.
Phospholipase B (PLB) catalyses the hydrolytic cleavage of both acylester bonds of glycerophospholipids. This family of PLB enzymes has been identified in mammals, flies and nematodes but not in yeast [, ]. In Drosophila this protein was named LAMA for laminin ancestor since it is expressed in the neuronal and glial precursors that surround the lamina [].This superfamily represents the domain 1 of phospholipase B. Structurally, this domain consists of 4 anti-parallel beta sheets and a small alpha helix.
Phospholipase B (PLB) catalyses the hydrolytic cleavage of both acylester bonds of glycerophospholipids. This family of PLB enzymes has been identified in mammals, flies and nematodes but not in yeast [, ]. In Drosophila this protein was named LAMA for laminin ancestor since it is expressed in the neuronal and glial precursors that surround the lamina [].This superfamily represents the domain 3 of phospholipase B.
This family consists of the protein beta-microseminoprotein/prostate-associated microseminoprotein from humans and some small serum protein from snakes. Prostatic secretory protein of 94 amino acids (PSP94), also called beta-microseminoprotein, is a small, nonglycosylated protein, rich in cysteine residues. It was first isolated as a major protein from Homo sapiens seminal plasma []. The exact function of this protein is unknown.The small serum proteins may serve as a self-defense protein against the toxic effects of the snake venom during accidental envenomation.
This domain is found in bacterial and viral proteins which are very similar to the Zonular occludens toxin (Zot). Zot is elaborated by bacteriophage present in toxigenic strains of Vibrio cholerae. Zot is a single polypeptide chain of 44.8kDa, with the ability to reversibly alter intestinal epithelial tight junctions, allowing the passage of macromolecules through mucosal barriers. The Zot biologically active domain was localized towards the C terminus of the protein []. This entry represents the N-terminal domain of Zot.
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 [].Exo84 is also involved in pre-mRNA splicing []and is required for epithelial polarity in Drosophila [, ].
This entry represents a family of bacterial proteins, including the outer membrane lipoprotein Flpp3 from Francisella tularensis (). This protein family was previously known as DUF3568. Flpp3, a virulence determinant of tularemia, shows a six stranded β-sheet supported with two crossing α-helices. It has a hydrophobic internal cavity that has been suggested to bind a small organic molecule. However, its specific function is still unknown [, ].
A number of different families of proteins share a conserved domain which was first characterised in some animal lectins and which seem to function as a calcium-dependent carbohydrate-recognition domain [, ]. This domain, which is known as the C-type lectin domain (CTL) or as the carbohydrate-recognition domain (CRD), consists of about 110 to 130 residues. There are four cysteines which are perfectly conserved and involved in two disulphide bonds.There are proteins with modules similar in overall structure to CRDs that serve functions other than sugar binding. Therefore, a more general term C-type lectin-like domain was introduced to refer to such domains, although both terms C-type lectin and C-type lectin-like are sometimes used interchangeably [].C-type lectins can be further divided into seven subgroups based on additional non-lectin domains and gene structure: (I) hyalectans, (II) asialoglycoprotein receptors, (III) collectins, (IV) selectins, (V) NK group transmembrane receptors, (VI) macrophage mannose receptors, and (VII) simple (single domain) lectins []. Lectins are a diverse group of proteins, both in terms of structure and activity. Carbohydrate binding ability may have evolved independently and sporadically in numerous unrelated families, where each evolved a structure that was conserved to fulfil some other activity and function. In general, animal lectins act as recognition molecules within the immune system, their functions involving defence against pathogens, cell trafficking, immune regulation and the prevention of autoimmunity [].
The dlt operon (dltA to dltD) of Lactobacillus rhamnosus 7469 encodes four proteins responsible for the esterification of lipoteichoic acid (LTA) by D-alanine. These esters play an important role in controlling the net anionic charge of the poly (GroP) moiety of LTA. DltA and DltC encode the D-alanine-D-alanyl carrier protein ligase (Dcl) and D-alanyl carrier protein (Dcp), respectively. Whereas the functions of DltA and DltC are defined, the functions of DltB and DltD are unknown. In vitroassays showed that DltD bound Dcp for ligation with D-alanine by Dcl in the presence of ATP. In contrast, the homologue of Dcp, the Escherichia coli acyl carrier protein (ACP), involved in fatty acid biosynthesis, was not bound to DltD and thus was not ligated with D-alanine. DltD also catalyzed the hydrolysis of the mischarged D-alanyl-ACP. The hydrophobic N-terminal sequence of DltD was required for anchoring the protein in the membrane. It is hypothesized that this membrane-associated DltD facilitates the binding of Dcp and Dcl for ligation of Dcp with D-alanine and that the resulting D-alanyl-Dcp is translocated to the primary site of D-alanylation [].
Activator protein-2 (AP-2) transcription factors constitute a family of closely related and evolutionarily conserved proteins that bind to the DNA consensus sequence 5'-GCCNNNGGC-3' and stimulate target gene transcription [, ]. Five different isoforms of AP-2 have been identified in mammals, termed AP-2 alpha, beta, gamma, delta and epsilon. Each family member shares a common structure, possessing a proline/glutamine-rich domain in the N-terminal region, which is responsible for transcriptional activation [], and a helix-span-helix domain in the C-terminal region, which mediates dimerisation and site-specific DNA binding [].The AP-2 family have been shown to be critical regulators of gene expression during embryogenesis. They regulate the development of facial prominence and limb buds, and are essential for cranial closure and development of the lens [, ]; they have also been implicated in tumorigenesis. AP-2 protein expression levels have been found to affect cell transformation, tumour growth and metastasis, and may predict survival in some types of cancer [, ]. Mutations in human AP-2 have been linked with bronchio-occular-facial syndrome and Char Syndrome, congenital birth defects characterised by craniofacial deformities and patent ductus arteriosus, respectively []. AP-2 gamma was originally isolated from murine carcinoma cells []. The gene was found to be expressed in several embryonic areas whose development can be affected by retinoids, such as the forebrain, face and limb buds []. A human homologue has also been identified which is involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer []. The protein was initially termed AP-2.2, but has since been reclassified as AP-2 gamma.
The B30.2 domain was first identified as a protein domain encoded by an exon (named B30-2) in the Homo sapiens class I major histocompatibility complex region [], whereas the SPRY domain was first identified in a Dictyostelium discoideum kinase splA and mammalian calcium-release channels ryanodine receptors []. B30.2 domain consists of PRY and SPRY subdomains. The SPRY domains (after SPla and the RYanodine Receptor) areshorter at the N terminus than the B30.2 domains. The ~200-residue B30.2/SPRY (for B30.2 and/or SPRY) domain is present in a large number of proteins with diverse individual functions in different biological processes. The B30.2/SPRY domain in these proteins is likely to function through protein-protein interaction [].The N-terminal ~60 residues of B30.2/SPRY domains are poorly conserved and, as a consequence, a new domain name PRY was coined for a group of similar sequence segments N-terminal to the SPRY domains []. The B30.2/SPRY domain contains three highly conserved motifs (LDP, WEVE and LDYE) []. The B30.2/SPRY domain adopts a highly distorted, compact β-sandwich fold with two additional short beta helices at the N terminus. The beta sandwich of the B30.2/SPRY domain consists of two layers of beta sheets: sheet A composed of eight strands and sheet B composed of seven strands. All the beta strands are in antiparallel arrangement []. The 5th β-strand corresponding to WEVE motif []. Both the N- and C-terminal ends of the B30.2/SPRY domains in general are close to each other [].
MSS4 (mammalian suppressor of Sec4) is an evolutionarily highly conserved protein, which is expressed in all mammalian tissues. Although it was first proposed to function as a guanine exchange factor (GEF) for Rab GTPases, it was soon described as a quite inefficient GEF and was thus suggested to function rather as a chaperone, protecting nucleotide free Rabs from degradation, than as a GEF [].The structure of MSS4 revealed a mostly beta fold stabilized by a Zn(2+) ion coordinated by cysteine residues from two CxxC motifs. The fold of the MSS4 domain consists of a central beta sheet (betaG-betaK) flanked by a beta hairpin (betaB-betaC) on one side and a small variable sheet on the other. A single Zn(2+) ion, coordinated by the thiol groups of cysteine residues from two CxxC motifs located in the betaB-betaC and betaI-betaJ loops, appears to play an important structural role by reinforcing the hydrophobic core formed by the betaB-betaC hairpin, the betaG-betaH loop, and the central beta sheet [, , ].
Cell fusion is fundamental for reproduction and organ formation. Fusion between most Caenorhabditis elegans epithelial cells is mediated by the EFF1 fusogen. AFF was first identified in EFF1 mutants. Cell fusion in all epidermal and vulval epithelia was blocked in EFF1 mutants. However, fusion between the anchor cell and the utse syncytium that establishes a continuous uterine-vulval tube proceeded normally []. AFF1 was established as necessary for this and for the fusion of heterologous cells in C. elegans [].The transmembrane forms of FF proteins, like most viral fusogens, possess an N-terminal signal sequence followed by a long extracellular portion, a predicted transmembrane domain, and a short intracellular tail. A striking conservation in the position and number of all 16 cysteines in the extracellular portion of FF proteins from different nematode species suggests that these proteins are folded in a similar 3D structure that is essential for their fusogenic activity []. C. elegans AFF1 and EFF1 proteins are essential for developmental cell-to-cell fusion and can merge insect cells. Thus FFs comprise an ancient family of cellular fusogens that can promote fusion when expressed on a viral particle [].
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Claudin-2 was initially isolated as a peptide fragment from TJ-enriched junctional cell fractions. Following sequencing and similarity searching it was cloned and expressed in cells, where it was shown to concentrate at TJs []. Human and mouse isoforms have been identified. Claudin-2 shares ~22-46% overall similarity with other claudin family members at the aminoacid level, displaying highest similarity to claudin-14.
The Factor for Inversion Stimulation (FIS) protein is a regulator ofbacterial functions, and binds specifically to weakly related DNA sequences []. It activates ribosomal RNA transcription, and is involved in upstreamactivation of rRNA promoters. Found in gamma proteobacterial microbes, theprotein has been shown to play a part in the regulation of virulence factorsin both Salmonella typhimurium and Escherichia coli []. Some of itsfunctions include inhibition of the initiation of DNA replication from theOriC site, and promotion of Hin-mediated DNA inversion [].In its C-terminal extremity, FIS encodes a helix-turn-helix (HTH) DNA-binding motif, which shares a high degree of similarity with other HTHmotifs of more primitive bacterial transcriptional regulators, such as thenitrogen assimilation regulatory proteins (NtrC) from species like Azobacter,Rhodobacter and Rhizobium. This has led to speculation that both evolvedfrom a single common ancestor []. Recently, the crystal structure of wild-type E. coli FIS was resolved, together with six mutants []- the first crystal structure wassolved in 1991. From the most recent 2.0A structure []of wild-typeFIS, the protein was observed to exist as a homodimer in the bacterialcytoplasm. By comparison with the structures of FIS mutants, it was deducedthat arginine-71 is critical for the binding of FIS to RNA polymerase, whileglycine-72 stabilises the tertiary structure.
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Claudin-8 was identified through searching expressed sequence tag (EST) databases for sequences similar to claudin-1 and -2 []. It was subsequently cloned and expressed in cells, where it was shown to concentrate at tight junctions. Human and mouse isoforms have been identified. Claudin-8 shares ~26-58% overall similarity with other claudin family members at the amino acid level, displaying highest similarity to claudin-17.Claudin-8 interacts with claudin-4 and recruits it to tight junction in the kidney. In the collecting duct, this interaction is required for the anion-selective paracellular pathway in which chloride reabsorption is coupled with sodium reabsorption [, ].
Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types [, , ]. They can also form heteropolymers with each other within and between tight junction strands []. Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 []. They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB [].Claudin-6 was identified through searching expressed sequence tag (EST)databases for sequences similar to claudin-1 and -2 []. It was subsequently cloned and expressed in cells, where it was shown to concentrate at tight junctions. Human and mouse isoforms have beenidentified. Claudin-6 shares ~25-70% overall similarity with other claudin family members at the amino acid level, displaying highest similarity to claudin-9.
The B30.2 domain was first identified as a protein domain encoded by an exon (named B30-2) in the Homo sapiens class I major histocompatibility complex region [], whereas the SPRY domain was first identified in a Dictyostelium discoideum kinasesplA and mammalian calcium-release channels ryanodine receptors []. B30.2 domain consists of PRY and SPRY subdomains. The SPRY domains (after SPla and the RYanodine Receptor) are shorter at the N terminus than the B30.2 domains. The ~200-residue B30.2/SPRY (for B30.2 and/or SPRY) domain is present in a large number of proteins with diverse individual functions in different biological processes. The B30.2/SPRY domain in these proteins is likely to function through protein-protein interaction [].The N-terminal ~60 residues of B30.2/SPRY domains are poorly conserved and, as a consequence, a new domain name PRY was coined for a group of similar sequence segments N-terminal to the SPRY domains []. The B30.2/SPRY domain contains three highly conserved motifs (LDP, WEVE and LDYE) []. The B30.2/SPRY domain adopts a highly distorted, compact β-sandwich fold with two additional short beta helices at the N terminus. The beta sandwich of the B30.2/SPRY domain consists of two layers of beta sheets: sheet A composed of eight strands and sheet B composed of seven strands. All the beta strands are in antiparallel arrangement []. The 5th β-strand corresponding to WEVE motif []. Both the N- and C-terminal ends of the B30.2/SPRY domains in general are close to each other [].This superfamily also matches diverse E3 ubiquitin-protein ligases. This protein is involved in the apoptosis process [, ].
RNA (C5-cytosine) methyltransferases (RCMTs) catalyse the transfer of a methyl group to the 5th carbon of a cytosine base in RNA sequences to produce C5-methylcytosine. RCMTs use the cofactor S-adenosyl-L-methionine (SAM) as a methyl donor []. The catalytic mechanism of RCMTs involves an attack by the thiolate of a Cys residue on position 6 of the target cytosine base to form a covalent link, thereby activating C5 for methyl-group transfer. Following the addition of the methyl group, a second Cys residue acts as a general base in the beta-elimination of the proton from the methylated cytosine ring. The free enzyme is restored and the methylated product is released [].Numerous putative RCMTs have been identified in archaea, bacteria and eukaryota [, ]; most are predicted to be nuclear or nucleolar proteins []. The Escherichia coli Ribosomal RNA Small-subunit Methyltransferase Beta (RSMB) FMU (FirMicUtes) represents the first protein identified and characterised as a cytosine-specific RNA methyltransferase. RSMB was reported to catalyse the formation of C5-methylcytosine at position 967 of 16S rRNA [, ].A classification of RCMTs has been proposed on the basis of sequence similarity []. According to this classification, RCMTs are divided into 8 distinct subfamilies []. Recently, a new RCMT subfamily, termed RCMT9, was identified []. Members of the RCMT contain a core domain, responsible for the cytosine-specific RNA methyltransferase activity. This 'catalytic' domain adopts the Rossman fold for the accommodation of the cofactor SAM []. The RCMT subfamilies are also distinguished by N-terminal and C-terminal extensions, variable both in size and sequence [].The prototypical member of the Nuclear protein 1 RCMT subfamily, the S. cerevisiae NCL1 (also known as Trm4), has been demonstrated to methylate cytosine to C5-methylcytosine at positions 34, 40, 48 and 49 in different intron- containing tRNAs and tRNA precursors []. Its human homologue, MISU/NSUN2, was found to catalyse the formation of C5-methylcytosine at position 34 of intron-containing pre-tRNAs []; it was not able to modify tRNAs at positions 48 or 49. It was also shown to be involved in Myc-mediated proliferation of cancer cells [].
Neurotransmitter transport systems are integral to the release, re-uptake and recycling of neurotransmitters at synapses. High affinity transport proteins found in the plasma membrane of presynaptic nerve terminals and glial cells are responsible for the removal from the extracellular space of released-transmitters, thereby terminating their actions []. Plasma membrane neurotransmitter transporters fall into two structurally and mechanistically distinct families. The majority of the transporters constitute an extensive family of homologous proteins that derive energy from the co-transport of Na+and Cl-, in order to transport neurotransmitter molecules into the cell against their concentration gradient. The family has a common structure of 12 presumed transmembrane helices and includes carriers for gamma-aminobutyric acid (GABA), noradrenaline/adrenaline, dopamine, serotonin, proline, glycine, choline, betaine and taurine. They are structurally distinct from the second more-restricted family of plasma membrane transporters, which are responsible for excitatory amino acid transport. The latter couple glutamate and aspartate uptake to the cotransport of Na+and the counter-transport of K+, with no apparent dependence on Cl-[]. In addition, both of these transporter families are distinct from the vesicular neurotransmitter transporters [, ].On the basis of behavioural interactions with mutations in the Shaker K+channel gene of Drosophila, mutations in a new gene, called inebriated(ine), were isolated. Considering the distinctive phenotype displayed bythese flies, it was postulated that the ine mutation might increaseneuronal excitability []. Subsequently the ine mutation was mapped, andthe gene was cloned. The ine gene encodes a protein of 658 amino acidswith a high degree of sequence similarity to members of the Na+/Cl--dependent neurotransmitter transporter superfamily. Therefore inemutations may cause increased excitability of the drosophila motor neuron,as a result of defective re-uptake of its substrate neurotransmitter,the identity of which remains to be determined []. This neurotransmitter is also important for perinerual gilial growth []and has also been shown to act as an osmolyte transporter [].
The large (alpha, GltB) subunit of bacterial glutamate synthase (GOGAT, GltS) consists of three domains. This entry represents a stand-alone version of the N-terminal amidotransferase domain that is found in archaeal GOGAT, where the large subunit is represented by three separate proteins corresponding to the three domains of the "standard"bacterial enzyme []. Similar organisation of GOGAT with stand-alone domains has been found in some bacteria (e.g., Sinorhizobium meliloti and Thermotoga maritima), but its function is not clear in those organisms where the "standard"(integrated) bacterial form is also present (e.g., Sinorhizobium meliloti).The amidotransferase domain of the bacterial GOGAT is characterised by a four layer alpha/beta/beta/alpha architecture []and contains the typical catalytic centre. The N-terminal Cys-1 catalyses the hydrolysis of L-glutamine generating ammonia and the first molecule of L-glutamate [].Originally, only the ORF encoding the central domain of GOGAT was recognised and annotated as GltB in archaea, and the rest of the large subunit was thought to be missing, which may lead to some misannotations []. This led to speculation that the archaeal form of the GOGAT large subunit was the ancestral minimal form of the enzyme. Later analysis showed, however, that in all archaea where the large subunit has been found, its entire sequence is represented by three separate ORFs [].Glutamate synthase is a complex iron-sulphur flavoprotein that catalyses the reductive synthesis of L-glutamate from 2-oxoglutarate and L-glutamine via intramolecular channeling of ammonia, a reaction in the bacterial, yeast and plant pathways for ammonia assimilation []. GOGAT is a multifunctional enzyme that functions through three distinct active centres carrying out multiple reaction steps: L-glutamine hydrolysis, conversion of 2-oxoglutarate into L-glutamate, and electron uptake from an electron donor [].
Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) []. It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals []. Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease [, ].Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important indevelopment []. Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other [].Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines []that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.The Wnt-2 gene was isolated from a human lung cDNA library in 1988 []. The protein was initially named IRP for Int-1 Related Protein and later termed Wnt-2. Northern blot analysis from a range of embryonic and adult tissues revealed that the gene was expressed almost exclusively in placenta and lung.Mutation of the mouse Wnt-2 gene leads to placental defects.
Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) []. It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals []. Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease [, ].Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important indevelopment []. Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other [].Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very littleis known about the structure of Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines []that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.The Wnt-3 gene was first identified in mouse in 1987, where it was found tobe expressed during embryogenesis and in adult brain. Insertion of proviralDNA from mouse mammary tumour virus (MMTV) occurs at the mouse Wnt-3 locus,leading to activation of the gene []. However, the human Wnt-3 gene was notfound to be amplified or rearranged in breast cancer tissues [].
This family includes the neuron-enriched endosomal proteins NSG1 (NEEP21), NSG2 (P19) and NSG3 (calcyon, Caly). They interact with distinct elements of the endosomal and synaptic scaffolding machinery []. NSG1 and NSG2 may not be resident endosomal proteins, and are also known as neuronal vesicle trafficking-associated proteins 1 and 2 respectively []. NSG1/NEEP21 plays a role in the trafficking of multiple receptors, including the cell adhesion molecule L1/NgCAM, the neurotransmitter receptor GluA2, and beta-APP []. The role of NSG2 is not known.It was originally thought that the Neuron-specific vesicular protein calcyon (previously known as D1 dopamine receptor-interacting, calcyon), interacted directly with the D1 dopamine receptor (DRD1) to modulate neocortical and hippocampal neuronal excitability as well as cAMP-dependent signalling []. However, this work was retracted, as it was shown that a direct interaction with the dopamine D1 receptor had been misinterpreted []. However, it has been shown that calcyon induces D1DR to stimulate intracellular Ca2+ release, and this suggests a possible functional interaction between calcyon and D1DR, despite there being, as yet, no direct interaction between them. A recent study suggested that calcyon-containing vesicles might transport D1DR by associating calcyon with D1DR through their assembly to clathrin []. However, as a single transmembrane protein, it is currently not clear how calcyon can regulate the internalization of D1DR from the plasma membrane to endocytic vesicles.Calcyon is a brain-specific protein, mainly localized in the intracellular endosomal vesicles of dendritic spines in dopamine expressing pyramidal cells in the prefrontal cortex and hippocampus and dorsal striatum region []. Neuron-specific vesicular protein calcyon has implicated in clathrin-mediated endocytosis. It is exclusively expressed in neurons, and localized in moving vesicles and it thought to play a role in brain plasticity []. Defective calcyon proteins have been implicated in both attention-deficit/hyperactivity disorder (ADHD) [, ]and schizophrenia [].
The B30.2 domain was first identified as a protein domain encoded by an exon (named B30-2) in the Homo sapiens class I major histocompatibility complex region [], whereas the SPRY domain was first identified in a Dictyostelium discoideum kinase splA and mammalian calcium-release channels ryanodine receptors []. B30.2 domain consists of PRY and SPRY subdomains. The SPRY domains (after SPla and the RYanodine Receptor) are shorter at the N terminus than the B30.2 domains. The ~200-residue B30.2/SPRY (for B30.2 and/or SPRY) domain is present in a large number of proteins with diverse individual functions in different biological processes. The B30.2/SPRY domain in these proteins is likely to function through protein-protein interaction [].The N-terminal ~60 residues of B30.2/SPRY domains are poorly conserved and, as a consequence, a new domain name PRY was coined for a group of similar sequence segments N-terminal to the SPRY domains []. The B30.2/SPRY domain contains three highly conserved motifs (LDP, WEVE and LDYE) []. The B30.2/SPRY domain adopts a highly distorted, compact β-sandwich fold with two additional short beta helices at the N terminus. The beta sandwich of the B30.2/SPRY domain consists of two layers of beta sheets: sheet A composed of eight strands and sheet B composed of seven strands. All the beta strands are in antiparallel arrangement []. The 5th β-strand corresponding to WEVE motif []. Both the N- and C-terminal ends of the B30.2/SPRY domains in general are close to each other [].Tripartite motif-containing proteins (TRIMs) play a variety roles in innate immunity. TRIM14 is a noncanonical TRIM that lacks an E3 ubiquitin ligase RING domain. It is involved in type I IFN signaling in innate immunity [, , ]. This entry represents the PRY/SPRY domain of TRIM14.
This is the B30.2/SPRY domain found in Ran binding proteins (RanBPs), such as RanBP M homologue (AtRanBPM) from Arabidopsis [], vacuolar import and degradation protein 30 (Vid30) from Saccharomyces cerevisiae and dual specificity protein kinase splA (SPLA) from Dictyostelium discoideum.The B30.2 domain was first identified as a protein domain encoded by an exon (named B30-2) in the Homo sapiens class I major histocompatibility complex region [], whereas the SPRY domain was first identified in a Dictyostelium discoideum kinase splA and mammalian calcium-release channels ryanodine receptors []. B30.2 domain consists of PRY and SPRY subdomains. The SPRY domains (after SPla and the RYanodine Receptor) are shorter at the N terminus than the B30.2 domains. The ~200-residue B30.2/SPRY (for B30.2 and/or SPRY) domain is present in a large number of proteins with diverse individual functions in different biological processes. The B30.2/SPRY domain in these proteins is likely to function through protein-protein interaction [].The N-terminal ~60 residues of B30.2/SPRY domains are poorly conserved and, as a consequence, a new domain name PRY was coined for a group of similar sequence segments N-terminal to the SPRY domains []. The B30.2/SPRY domain contains three highly conserved motifs (LDP, WEVE and LDYE) []. The B30.2/SPRY domain adopts a highly distorted, compact β-sandwich fold with two additional short beta helices at the N terminus. The beta sandwich of the B30.2/SPRY domain consists of two layers of beta sheets: sheet A composed of eight strands and sheet B composed of seven strands. All the beta strands are in antiparallel arrangement []. The 5th β-strand corresponding to WEVE motif []. Both the N- and C-terminal ends of the B30.2/SPRY domains in general are close to each other [].
This entry represents a group of subtilisin-like proteases mostly from plants and bacteria. Proteins in this entry include melon cucumisin, Arabidopsis thaliana Ara12, a nodule specific serine protease from Alnus glutinosa ag12, members of the tomato P69 family, and tomato LeSBT2. These proteins belong to the peptidase S8 family. Cucumisin from the juice of melon fruits is a thermostable serine peptidase, with a broad substrate specificity for oligopeptides and proteins. A. thaliana Ara12 is a thermostable, extracellular serine protease, found chiefly in silique tissue and stem tissue. Ara12 is stimulated by Ca2+ ions. A. glutinosa ag12 is expressed at high levels in the nodules, and at low levels in the shoot tips; it is implicated in both symbiotic and non-symbiotic processes in plant development. The tomato P69 protease family is comprised of various protein isoforms of approximately 69kDa. These isoforms accumulate extracellularly. Some of the P69 genes are tightly regulated in a tissue specific fashion, and by environmental and developmental signals. For example: infection with avirulent bacteria activates transcription of the genes for the P69 B and C isoforms, the P69 E transcript was detected only in roots, and the P69F transcript only in hydathodes. The Tomato LeSBT2 subtilase transcript was not detected in flowers and roots, but was present in cotyledons and leaves. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.
Amphiphysins belong to the expanding BAR (Bin-Amphiphysin-Rvsp) family proteins, all members of which share a highly conserved N-terminal BAR domain, which has predicted coiled-coil structures required for amphiphysin dimerisation and plasma membrane interaction []. Almost all members also share a conserved C-terminal Src homology 3 (SH3) domain, which mediates their interactions with the GTPase dynamin and the inositol-5'-phosphatase synaptojanin 1 in vertebrates and with actin in yeast. The central region of all these proteins is most variable. In mammals, the central region of amphiphysin I and amphiphysin IIa contains a proline-arginine-rich region for endophilin binding and a CLAP domain, for binding to clathrin and AP-2. The interactions mediated by both the central and C-terminal domains are believed to be modulated by protein phosphorylation [, ].Amphiphysins are proteins involved in clathrin-mediated endocytosis clathrin-mediated endocytosis, actin function, and signalling pathways [, ].Amphiphysin 1 was first identified in 1992 as a brain protein that was partially-associated with synaptic vesicles. Following its cloning, it was also realised to be a human auto-antigen that is detected in a rare neurological disease, Stiff-Man Syndrome, and also in certain types of cancer []. Amphiphysin 1 senses and facilitates membrane curvature to mediate synaptic vesicles invagination and fission during newly retrieved presynaptic vesicle formation and also acts as a linker protein binding with dynamin, clathrin, Amphiphysin II, and other dephosphins in the clathrin-coated complex. Amphiphysin 1 is cleaved an asparagine endopeptidase (AEP), which generates afragment that increases with aging. This fragment disrupts the normal endocytic function of Amphiphysin 1, leading to synaptic dysfunction, as it activates CDK5 inducing tau hyperphosphorylation. Therefore, Amphiphysin 1 posttranslational modification contributes to pathogenesis of Alzheimer's disease, being the AEP a therapeutic target [].
The WH2 (WASP-Homology 2, or Wiskott-Aldrich homology 2) domain is an ~18 amino acids actin-binding motif. This domain was first recognised as an essential element for the regulation of the cytoskeleton by the mammalian Actin nucleation-promoting factor WAS (also known asWiskott-Aldrich syndrome protein, WASP). WH2 proteins occur in eukaryotes from yeast to mammals, in insect viruses, and in some bacteria. The WH2 domain is found as a modular part of larger proteins; it can be associated with the WH1 or EVH1 domain and with the CRIB domain , and the WH2 domain can occur as a tandem repeat. The WH2 domain binds actin monomers and can facilitate the assembly of actin monomers into newly forming actin filaments [, ]. Some proteins known to contain a WH2 domain:Mammalian Actin nucleation-promoting factor WAS (WASP), a possible regulator of lymphocyte and platelet function. Defects in WASP are the cause of Wiskott- Aldrich syndrome (WAS), an X-linked recessive disease characterised by immune dysregulation and microthrombocytopenia. WASP proteins bind the actin nucleating protein complex Arp2/3.Mammalian N-WASP/WASL and WASF/SCAR/WAVE1-3, and yeast LAS17, which are also proteins from the WASP family that participate in the transduction of signals from the cell surface to the actin cytoskeleton.WAS protein family homologue 1 (WASH1), acts as a nucleation-promoting factor at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerisation. Baker's yeast Verprolin, a protein involved in cytoskeletal organisation and cellular growth.Human WASP interacting protein (WASPIP/WIP), a WASP-, profilin- and actin-binding protein which induces actin polymerisation and redistribution.Nuclear polyhedrosis virus (NPV) P61/78/83 capsid protein, which may be important for the persistence and survival of the virus.Fruit fly Spir(e) protein, an actin nucleation factor involved in the development of oocytes and embryos. Spir is conserved among metazoans.Mammalian metastasis suppressor 1 or Missing in Metastasis (MIM) protein, an actin-binding protein that may be related to cancer progression or tumor metastasis.
Transcriptional activation and repression is required for control of cell proliferation and differentiation during embryonic development and homeostasis in the adult organism. Perturbations of these processes can lead to the development of cancer []. The Eight-Twenty-One (ETO) gene product is able to form complexes with corepressors and deacetylases, such as nuclear receptor corepressor (N-CoR), which repress transcription when recruited by transcription factors []. The ETO gene derives its name from its association with many cases of acute myelogenous leukaemia (AML), in which a reciprocal translocation, t(8;21), brings together a large portion of the ETO gene from chromosome eight and part of the AML1 gene from chromosome 21. The human ETO gene family currently comprises three major subfamilies: ETO/myeloid transforming gene on chromosome 8 (MTG8); myeloid transforming gene related protein-1 (MTGR1) and myeloid transforming gene on chromosome 16 (MTG16). ETO proteins are composed of four evolutionarily conserved domains termed nervy homology regions (NHR) 1-4. NHR1 is thought to stabilise the formation of high molecular weight complexes, but is not directly responsible for repressor activity. NHR2 and its flanking sequence comprise the core repressor domain, which mediates 50% of the wild type repressor activity. Furthermore, there is evidence that the amphipathic helical structure of NHR2 promotes the formation of ETO/AML1 homodimers []. NHR3 and NHR4 have been shown to act in concert to bind N-CoR. NHR4 contains two zinc finger motifs, which are thought to play a role in protein interactions rather than DNA binding []. The ultrabithorax (Ubx) gene is a homeotic gene in Drosophila that determines the morphological characteristics of each segment. Ubiquitous expression of Ubx gave rise to increased expression of several mRNAs; one of these transcripts was localised to the nervous system precursor cells of the head, thoracic and abdominal segments, and was termed nervy. Analysis of nervy cDNA revealed that it shared significant sequence similarity with the human ETO gene; it was also found to contain a region of similarity to the TATA binding protein-associated factor TAF110 [].
RNA (C5-cytosine) methyltransferases (RCMTs) catalyse the transfer of a methyl group to the 5th carbon of a cytosine base in RNA sequences to produce C5-methylcytosine. RCMTs use the cofactor S-adenosyl-L-methionine (SAM) as a methyl donor []. The catalytic mechanism of RCMTs involves an attack by the thiolate of a Cys residue on position 6 of the target cytosine base to form a covalent link, thereby activating C5 for methyl-group transfer. Following the addition of the methyl group, a second Cys residue acts as a general base in the beta-elimination of the proton from the methylated cytosine ring. The free enzyme is restored and the methylated product is released [].Numerous putative RCMTs have been identified in archaea, bacteria and eukaryota [, ]; most are predicted to be nuclear or nucleolar proteins []. The Escherichia coli Ribosomal RNA Small-subunit Methyltransferase Beta (RSMB) FMU (FirMicUtes) represents the first protein identified and characterised as a cytosine-specific RNA methyltransferase. RSMB was reported to catalyse the formation of C5-methylcytosine at position 967 of 16S rRNA [, ].A classification of RCMTs has been proposed on the basis of sequence similarity []. According to this classification, RCMTs are divided into 8 distinct subfamilies []. Recently, a new RCMT subfamily, termed RCMT9, was identified []. Members of the RCMT contain a core domain, responsible for the cytosine-specific RNA methyltransferase activity. This 'catalytic' domain adopts the Rossman fold for the accommodation of the cofactor SAM []. The RCMT subfamilies are also distinguished by N-terminal and C-terminal extensions, variable both in size and sequence [].Proteins related to the RsmB subfamily of RCMTs have been detected in the genomes of Viridiplantae []. They were provisionally assigned to the RsmB subfamily [], which hitherto was considered to be restricted to Eubacteria, based solely on similarity to the prototypic member of this subfamily, the E.coli protein [, ].
Cell fusion is fundamental for reproduction and organ formation. Fusion between most Caenorhabditis elegans epithelial cells is mediated by the EFF1 fusogen. AFF was first identified in EFF1 mutants. Cell fusion in all epidermal and vulval epithelia was blocked in EFF1 mutants. However, fusion between the anchor cell and the utse syncytium that establishes a continuous uterine-vulval tube proceeded normally []. AFF1 was established as necessary for this and for the fusion of heterologous cells in C. elegans [].The transmembrane forms of FF proteins, like most viral fusogens, possess an N-terminal signal sequence followed by a long extracellular portion, a predicted transmembrane domain, and a short intracellular tail. A striking conservation in the position and number of all 16 cysteines in the extracellular portion of FF proteins from different nematode species suggests that these proteins are folded in a similar 3D structure that is essential for their fusogenic activity []. C. elegans AFF1 and EFF1 proteins are essential for developmental cell-to-cell fusion and can merge insect cells. Thus FFs comprise an ancient family of cellular fusogens that can promote fusion when expressed on a viral particle [].Cell-cell fusogen EFF/AFF is a three domain protein involved in cell fusion, a process that is essential for development. These proteins can be found either as a monomer or trimer. Crystal structures of the trimer show unambiguous structural homology to class II viral fusion proteins in their characteristic post-fusion hairpin conformation. The trimer subunits feature the three class II beta sandwich domains, termed I, II, and III, organised in the same way as in the viral proteins [].This superfamily represents the domain 3 of the cell-cell fusogen EFF/AFF protein.
SSFA2, also known as Ki-ras-induced actin-interacting protein (KRAP), interacts with inositol 1,4,5-trisphosphate receptor (IP3R, also known as ITPR) []. SSFA2 was first localised as a membrane-bound form with extracellular regions suggesting it might be involved in the regulation of filamentous actin and signals from the outside of the cells []. It has now been shown to be critical for the proper subcellular localisation and function of IP3R. Inositol 1,4,5-trisphosphate receptor functions as the Ca2+ release channel on specialised endoplasmic reticulum membranes, so the subcellular localisation of IP3R is crucial for its proper function [].
The LysM (lysin motif) domain is a small globular domain, approximately 40 amino acids long. It is a widespread protein module involved in binding peptidoglycan in bacteria and chitin in eukaryotes. The domain was originally identified in enzymes that degrade bacterial cell walls [], but proteins involved in many other biological functions also contain this domain. It has been reported that the LysM domain functions as a signal for specific plant-bacteria recognition in bacterial pathogenesis []. Many of these enzymes are modular and are composed of catalytic units linked to one or several repeats of LysM domains. LysM domains are found in bacteria and eukaryotes [].
This domain is found in MORC proteins in eukaryotes and possesses a structure similar to the second domain of ribosomal S5 proteins. Arabidopsis microrchidia (MORC) ATPase family proteins are conserved among plants and animals and are involved in transcriptional silencing. In Arabidopsis, MORC6/DMS11 was reported to function in the condensation of pericentromeric heterochromatin, thereby facilitating transcriptional silencing []. Further studies demonstrate that MORC6 and its homologs MORC1 and MORC2 form a complex which associates with SUVH9, required for Pol V occupancy in the RdDM (RNA-directed DNA methylation) pathway.
This entry represents the C-terminal domain of katanin 80kDa subunit. Katanin is a microtubule-severing protein consist of a 60kDa ATPase subunit (katanin-p60) and a 80kDa subunit (katanin-p80) []. Katanin-p80is composed of an N-terminal WD40 repeat domain, a central proline-rich domain and a C-terminal domain required for dimerisation with the catalytic katanin-p60. The katanin complex associates with a specific subregion of the mitotic spindle leading to increased microtubule disassembly and targeting of katanin-p60 to the spindle poles []. It was suggested that katanin is targeted to spindle poles through a combination of direct microtubule binding by the katanin-p60 and through interactions between the WD40 domain and an unknown protein [].
Archaeal flagella are unique motility structures, and the absence of bacterial structural motility genes in the complete genome sequencesof flagellated archaeal species has always suggested that archaeal flagellar biogenesis is likely mediated by novel components. FlaD and FlaE, are present in the cell asmembrane-associated proteins but are not major components of isolated flagellar filaments. Interestingly, flaD was found to encodetwo proteins, each translated from a separate ribosome binding site.This entry represents a domain found in the N-teminal region of flaE but towards the C-terminal region of flaD [].
JMY (junction-mediating and -regulatory protein) []and WHAMM (WASP homologue-associated protein with actin, membranes and microtubules) []are two nucleation-promoting factors (NPFs) with similar domain architecture. JMY was originally identified as a transcriptional co-factor in the p53-response to DNA damage. Aside from this nuclear function, JMY is involved in cytoskeleton remodelling and trans-Golgi transport []. WHAMM binds microtubules and is involved in ER to cis-Golgi transport []. JMY and WHAMM show similar localisation and could be involved in similar processes []. This middle domain is the coiled-coil region that putatively binds microtubules to the scaffold. This ability to interact with microtubules plays a role in membrane tubulation.
Tsg was identified in Drosophila melanogaster as being required to specify the dorsal-most structures in the embryo, for example the amnioserosa. Biochemical experiments have revealed three key properties of Tsg: it can synergistically inhibit Dpp/BMP action in both D. melanogaster and vertebrates by forming a tripartite complete between itself, SOG/chordin and a BMP ligand; Tsg seems to enhance the Tld/BMP-1-mediated cleavage rate of SOG/chordin and may change the preference of site utilisation; Tsg can promote the dissociation of chordin cysteine-rich-containing fragments from the ligand to inhibit BMP signalling [, ].
This entry represents the probable inorganic carbon transporter subunit DabA, which is part of an energy-coupled inorganic carbon pump together with DabB subunit in DAB operons (DAB1 and DAB2), found in a wide range of bacteria and archaea. DAB operon is required for CO2 concentrating mechanisms []. The substrate of this subunit may be CO2 rather than carbonate ions based on kinetic calculations and in experimental assays in which E.coli was deleted of its carbonic anhydrase genes and expression of DAB2 operon restores its growth. Structural homology modelling suggests that DabA contains a domain that is distantly homologous to a type II beta-carbonic anhydrase (CA).
Repeats found in the Mus musculus (Mouse) and Homo sapiens (Human) THEG (testicularhaploid expressed gene) proteins and several Drosophila melanogaster (Fruit fly) proteins[].This repeat is the only conserved part of the THEG proteins from vertebrate spermatids. Both human and mouse THEG are specifically expressed in the nucleus of haploid male germ cells and are involved in the regulation of nuclear functions [, ]. Although the differential gene expression of THEG in spermatid-Sertoli cell co-culture supports the relevance of germ cell-Sertoli cell interaction for gene regulation during spermatogenesis, THEG was not found to be essential for spermatogenesis in mice [].
The gamma-secretase-activating protein (GSAP) family includes the mammalian GSAPs and the insect pigeon proteins (also known as linotte proteins). GSAP is a gamma-secretase regulator. It specifically activates the production of beta-amyloid protein through interactions with both gamma-secretase and its substrate, the amyloid precursor protein carboxy-terminal fragment (APP-CTF) []. This has led to interest in the protein as potential therapeutic target for the treatment of Alzheimer's disease []. Pigeon/linotte was initially identified as a gene that functions in adult Drosophila during associative learning [].This entry represents a domain found in the C-terminal of GSAP family members.
This family of proteins describes the Nqr2 (NqrB) subunit of the bacterial 6-subunit sodium-translocating NADH-ubiquinone oxidoreductase (i.e. a respiration linked sodium pump). In Vibrio cholerae, it negatively regulates the expression of virulence factors through inhibiting (by an unknown mechanism) the transcription of the transcriptional activator ToxT [].The family also includes RnfD, which is a subunit of the Rnf complex, a ferredoxin:NAD+ oxidoreductase that appears to translocate different ions (protons or sodium) in different bacteria []. The similarity of RnfD to NADH-ubiquinone oxidoreductases was previously noted [].
This is an NSD-specific Cys-His rich region (C5HCH) domain. Proteins containing this domain include NSD (nuclear receptor SET domain-containing) proteins. This domain is located on the C-terminal of NSD1, 2 and 3 proteins. C5HCH domain lies adjacent to the fifth plant homeodomain (PHD5). The PHD5-C5HCH module of NSD3 (PHD5-C5HCHNSD3) recognises the H3 N-terminal peptide containing unmodified K4 and trimethylated K9. Moreover, it has been reported that the PHD5-C5HCH module of NSD1 (PHD5-C5HCH) was the sole region required for tight binding of the NUP98-NSD1 fusion protein to the HoxA9 gene promoter, implicating that PHD5-C5HCH might have chromatin targeting ability [].
The MKRN protein family includes the ribonucleoproteins that are characterised by a variety of zinc-finger motifs, including typical arrays of one to four C3H1-type zinc fingers and a C3HC4-type RING-HC finger. Another motif rich in Cys and His residues (CH), with so far unknown function, is also generally present in MKRN proteins. MKRN proteins may have E3 ubiquitin ligase activity [, ]. At least four makorin genes exist in vertebrates [].Makorin 3 was first identified in the Prader-Willi syndrome critical region in the human genome, but has no obvious role in the disease [].
Synaptonemal complex protein 2 (SYCP2) N-terminal region contains two separate subdomains an ARLD (armadillo-repeat-like domain) and an SLD (Spt16M-like domain). The ARLD domain belongs to the armadillo-repeat protein family. Armadillo-repeat units often form a superhelix, which typically provides a platform for many protein partners that transduce Wnt signaling, such as beta-catenin. The ARLD of mouse SYCP2 was found to associate with different protein partners, including CENP J and CENP F. ARLD structure is highly similar to that of the 'required for cell differentiation (RCD-1)' protein [].
In archaea the enzyme tetrahydromethanopterin S-methyltransferase is composed of eight subunits, MtrA-H. The enzyme is a membrane- associated enzyme complex which catalyzes an energy-conserving, sodium-ion-translocating step in methanogenesis from hydrogen and carbon dioxide []. Subunit MtrH catalyzes the methylation reaction and was shown to exhibit methyltetrahydromethanopterin:cob(I)alamin methyltransferase activity [].CH3-H4MPT + cob(I)alamin -->H4MPT + CH3-cob(III)alamin (H4MPT = tetrahydromethanopterin)Methyltransferase MtxH from the archaea Methanosarcina may be part of a complex composed of 3 subunits; MtxA, MtxH and MtxX [].This entry also includes methylcorrinoid:tetrahydrofolate methyltransferase from Desulfitobacterium hafniense, which in vitro catalyses the transfer of a methyl group from methylcobalamin to tetrahydrofolate. In vivo this may permit anaerobic methylotrophic growth using glycine betaine [].
This entry includes a group of sucrose phosphorylases, including sucrose 6(F)-phosphate phosphorylase (Tthe_1921) from Thermoanaerobacterium thermosaccharolyticum, as well as glucosylglycerate phosphorylase. Tthe_1921 catalyses the reversible phosphorolysis of sucrose 6(F)-phosphate. It also acts on sucrose, D-fructose, alpha-D-glucose 1-phosphate and D-fructose 6-phosphate []. Glucosylglycerate phosphorylase (part of subfamily 18 of glycoside hydrolase family 13 (GH13_18) in CAZy) was previously thought to also function as a sucrose phosphorylase. However, subsequent studies have shown it to be a glucosylglycerate phosphorylase, and to have no activity on sucrose [].
This is a eukaryotic/eumetazoan PIN like domain found in the C-terminal region of bilateral ZNF451 proteins such as isoform 1 of human ZNF451. ZNF451 was shown to interact with p300 by the PIN-like domain and to negatively regulate TGF-beta signalling in a p300-dependent and sumoylation-independent manner. This domain is suggested to posses a potential active nuclease due to the presence of at least four conserved Asp residues in the predicted active site. Furthermore, it contains several conserved Cys and His residues, which may suggest stabilization of the domain structure with an embedded short zinc-binding loop [].
Proteins containing this repeat include the stress response protein Ish1 from fission yeasts and meiotic sister chromatid recombination protein 1 (Msc1) from budding yeasts. Proteins containing this repeat also include some uncharacterised proteins from Acinetobacter baumannii. Ish1 has a role in maintaining cell viability during stationary phase induced by stress response. It can be activated by the spc1 MAPK pathway []. Msc1 was identified in a screen for mutants that show an increase in meiotic unequal sister-chromatid recombination (SCR) []. Its function is not clear.
The highly conserved and essential protein Ssu72 has intrinsic phosphatase activity and plays an essential role in the transcription cycle. Ssu72 was originally identified in a yeast genetic screen as enhancer of a defect caused by a mutation in the transcription initiation factor TFIIB []. It binds to TFIIB and is also involved in mRNA elongation. Ssu72 is further involved in both poly(A) dependent and independent termination. It is a subunit of the yeast cleavage and polyadenylation factor (CPF), which is part of the machinery for mRNA 3'-end formation. Ssu72 is also essential for transcription termination of snRNAs [].
L-fucose isomerase () converts the aldose L-fucose into the corresponding ketose L-fuculose during the first step in fucose metabolism 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 []. L-arabinose isomerase (AraA) () catalyses the conversion of L-arabinose to L-ribulose as the first step in the pathway of L-arabinose utilization as a carbon source [].L-arabinose isomerase adopts a protein fold most similar to fucose isomerase despite low sequence identity []. This entry represents a C-terminal structural domain common to L-fucose and L-arabinose isomerases.
This group of proteins have a conserved C-terminal region which is found in LMBR1 and in the lipocalin-1 receptor. LMBR1 was thought to play a role in preaxial polydactyly, but recent evidence now suggests this not to be the case []. Vertebrate members of this family may play a role in limb development []. Lysosomal cobalamin transport escort protein LMBD1 is a lysosomal membrane chaperone required to export cobalamin from lysosome to the cytosol, allowing its conversion to cofactors [, ]. This protein showed homology to the lipocalin membrane receptor (LIMR) [].
This family of proteins which includes Bacteriophage T4 endonuclease VII, Mycobacteriophage D29 gene 59, and other as yet uncharacterised proteins. The T4 endonuclease VII (Endo VII) recognises a broad spectrum of DNA substrates ranging from branched DNAs to single base mismatches. The structure of this enzyme has been resolved and it was found that the monomers form an elongated, intertwined molecular dimer that exibits extreme domain swapping. Two pairs of antiparallel helices which form a novel 'four-helix cross' motif are the major dimerisation elements [].
YdaS is atranscription factor found in the cryptic prophage Rac of E. coli K12 and represents a novel family within the HigA superfamily as it is distantly related to HigA antitoxins. YdaS can act as a toxin whose expression is regulated by RacR and behaves as a monomer in solution [, ]. Previously, it was thought to be an antitoxin that neutralises the toxin YdaT []. This entry also includes some bacteriophage proteins, such as cro from Pseudomonas phage D3 and gene 30 protein from Enterobacteria phage phi80.
Synonym: dark protochlorophyllide reductaseProtochlorophyllide reductase catalyzes the reductive formation of chlorophyllide from protochlorophyllide during biosynthesis of chlorophylls and bacteriochlorophylls. The light-independent (dark) form of protochlorophyllide reductase plays a key role in the ability of gymnosperms, algae, and photosynthetic bacteria to form chlorophyll in the dark. Genetic and sequence analyses have indicated that dark protochlorophyllide reductase consists of three protein subunits that exhibit significant sequence similarity to the three subunits of nitrogenase, which catalyzes the reductive formation of ammonia from dinitrogen. Dark protochlorophyllide reductase activity was shown to be dependent on the presence of all three subunits, ATP, and the reductant dithionite [].
This family consists of YgfN, whose function is not clear. YgfN was identified as a molybdenum-binding subunit of a putative molydbopterin-containing selenate reductase complex consisting of proteins YgfK, YgfM and YgfN [, ]. However, another study showed that a mutation in the gene (b2881) encoding this protein conferred sensitivity to adenine, which is associated with impaired synthesis of guanine nucleotides from adenine during purine salvage []. YgfN is also known as XdhD, as it has been suggested to be a molybdenum-containing protein of the xanthine oxidase family [].
UL16 protein (also known as cytoplasmic envelopment protein 2) plays a role in capsid maturation including DNA packaging/cleavage []. In immunofluorescence studies [], UL16 was localised to the nucleus of infected cells in areas containing high concentrations of Human herpesvirus 2 (Herpes simplex virus 2) capsid proteins. These nuclear compartments have been described previously as viral assemblons []and are distinct from compartments containing replicating DNA. Localization within assemblons argues for a role of UL16 encoded protein in capsid assembly or maturation [].UL94 is a human cytomegalovirus (HCMV) homologue that has been shown to be involved in facilitating secondary envelopment of virions [].
DNA polymerase epsilon is essential for cell viability and chromosomal DNA replication in budding yeast. In addition, DNA polymerase epsilon may be involved in DNA repair and cell-cycle checkpoint control. The enzyme consists of at least four subunits in mammalian cells as well as in yeast. The largest subunit of DNA polymerase epsilon is responsible for polymerase activity. In mouse, the DNA polymerase epsilon subunit B is the second largest subunit of the DNA polymerase. A part of the N-terminal was found to be responsible for the interaction with SAP18. Experimental evidence suggests that this subunit may recruit histone deacetylase to the replication fork to modify the chromatin structure [].
This domain is found in a group of prokaryotic proteins which includes Escherichia coli MazG, which hydrolyses all canonical nucleoside triphosphates but it also might have a 'housecleaning' function by hydrolysing noncanonical NTPs, whose incorporation into the nascent DNA leads to the increased mutagenesis and DNA damage [, , ]. Phylogenetic distribution studies of this domain revealed that it commonly appears as two domains in tandem, although there are single-domain analogs. In E. coli there are two tandem globular domains, in which the NTPase activity was observed only at the C-terminal domain [].
Formin-binding protein 1 (FNBP1, also known as formin-binding protein 17) contains a N-terminal FER-CIP4 homology (FCH) domain and a C-terminal SH3 domain. It belongs to the CIP4 (Cdc42 interacting protein-4) subfamily of the F-BAR protein family. F-BAR proteins (F for FCH, Fer-CIP4 homology domain) are proteins with an extended CIP4-Fer domain. The F-BAR proteins have been implicated in cell membrane processes such as membrane invagination, tubulation and endocytosis []. FNBP1 was originally isolated as a molecule that binds to the proline-rich region of formin []. It induces tubular membrane invaginations and participates in endocytosis []. It interacts with sorting nexin, SNX2, and is linked to acute myelogeneous leukemia [].
Members of this protein family are HemK, a protein once thought to be involved in heme biosynthesis but now recognised to be a protein-glutamine methyltransferase that modifies the peptide chain release factors []. All members of the seed alignment are encoded next to the release factor 1 gene (prfA) and confirmed by phylogenetic analysis. However, the family is diverse enough that even many members of the seed alignment do not score above the seed alignment, which was set high enough to exclude all instances of PrmB.
Cytokine-inducible SH2-containing protein (CIS) is a member of the suppressor of cytokine signaling (SOCS) family proteins. CIS is involved in the negative regulation of cytokines that signal through the JAK-STAT5 pathway such as erythropoietin, prolactin and interleukin 3 (IL3) receptor. It inhibits STAT5 trans-activation by suppressing its tyrosine phosphorylation [].Suppressor of cytokine signalling (SOCS) was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain [, ].
The solute carrier family 10 (SLC10) comprises influx transporters of bile acids, steroidal hormones, various drugs, and several other substrates. Some members of the family are orphan carriers. The name "bile acid transporter family"arose because the first two SLC10 members characterised (NTCP/SLC10A1 and ASBT/SLC10A2) were primarily bile acid transporters [, ].Solute carrier family 10 member 4 (SLC10A4) is a synaptic vesicule monoaminergic and cholinergic associated transporter important for neuromodulation [, ]. SLC10A4 is still regarded an orphan transporter, although a protease-modified variant was recently reported to transport bile acids [].
LIM domain and actin-binding protein 1 (LIMA1, also know as EPLIN) is a cytoskeleton-associated protein that regulates actin dynamics by cross-linking and stabilising filaments []. It was first identified as the product of a gene that is transcriptionally down-regulated or lost in a number of human epithelial tumor cells [, ]. In humans, there are two EPLIN isoforms, EPLIN alpha and EPLIN beta, both have a centrally located LIM domain that may mediate self-dimerisation. EPLIN inhibits Arp2/3 complex-mediated branching nucleation of actin filaments and stabilises actin filament networks []. EPLIN can be regulated through phophoryltion by extracellular signal-regulated kinase (ERK) [].
This entry represents the gamma-secretase-activating protein (GSAP) family, whose members include the mammalian GSAPs and the insect pigeon proteins (also known as linotte proteins). GSAP is a gamma-secretase regulator. It specifically activates the production of beta-amyloid protein through interactions with both gamma-secretase and its substrate, the amyloid precursor protein carboxy-terminal fragment (APP-CTF) []. This has led to interest in the protein as potential therapeutic target for the treatment of Alzheimer's disease []. Pigeon/linotte was initially identified as a gene that functions in adult Drosophila during associative learning [].
This family consists of SLAIN motif-containing proteins, including SLAIN1 and SLAIN2. SLAIN1 was named after the SLAIN amino acid stretch in its C terminus. It is expressed at the stem cell and epiblast stages of ESC differentiation and in the epiblast, nervous system, tailbud and somites of the developing embryo in mice []. SLAIN2 has been shown to bind to the plus end of microtubules and to regulate microtubule dynamics and organisation. It promotes cytoplasmic microtubule nucleation and elongation. It is required for normal structure of the microtubule cytoskeleton during interphase [].
Class III alcohol dehydrogenases (ADH3) () tend to show poor activity for ethanol among their various substrate alcohols. They catalyze the oxidation and reduction of a wide variety of substrates that include S-(hydroxymethyl)glutathione (HMGSH), S-nitrosoglutathione, and long chain primary alcohols and aldehydes []. The enzyme was previously designated as glutathione-dependent formaldehyde dehydrogenase, as it acts as a HMGSH dehydrogenase (). ADH3 oxidizes HMGSH to S-formylglutathione, which is then hydrolyzed to glutathione and formate by a hydrolase [, ]. S-(hydroxymethyl)glutathione can form spontaneously from formaldehyde and glutathione, and constitutes a cellular strategy for sequestering and metabolizing highly toxic formaldehyde [].
TRBP2 was first identified as a HIV-1 TAR RNA-binding protein []. TRBP2 is a component of the RISC loading complex (RLC), which functions in RNA-mediated gene silencing (RNAi). It is a double-stranded RNA (dsRNA)-binding protein that associates with endonuclease Dicer, which cleaves precursor RNA molecules to produce microRNAs (miRNAs) and short interfering RNAs (siRNAs) in RNAi pathway []. Together with another dsRNA-binding protein, PACT, they function as key regulators of miRNA and siRNA biogenesis by Dicer in substrate recognition, binding, processing and RISC loading [].
The tripartite ATP-independent periplasmic (TRAP) transport system is firmly established as a new type of extracytoplasmic solute receptor (ESR)-dependent uptake systems, unrelated to ABC transporters. In TRAP transport systems the driving force for solute accumulation is an electrochemical ion gradient and not ATP hydrolysis []. The first TRAP transporter to be characterised was the high-affinity C4-dicarboxylate transport (Dct) system from Rhodobacter capsulatus []. This consists of three proteins; an ESR (DctP) and small (DctQ) and large (DctM) integral membrane proteins.This entry represents a family of TRAP transporter permease proteins, including DctM, SiaM (involved in sialic acid uptake []) and YiaN (involved in the uptake of 2,3-diketo-L-gulonate [, ]).
This group of ADP-dependent acetyl-CoA synthetases (ACS) act in the direction of acetate and ATP production in the organisms in which they have been characterised [, , ]. In most species this protein is bifunctional, existing as fused α-β domains. In Pyrococcus and related species, however, the domains exist as separate polypeptides. This entry represents the alpha (N-terminal) domain. In Pyrococcus and related species there appears to have been the development of a paralogous family such that four other proteins are close relatives. One of these (along with its beta-domain partner) was characterised as ACS-II showing specificity for phenylacetyl-CoA []. This entry excludes non-ACS-I paralogs.
This entry contains Influenza virus matrix protein 2. It is an integral membrane protein that is expressed on the infected cell surface and incorporated into virions where it is a minor component. The protein spans the viral membrane with an extracellular amino-terminus and a cytoplasmic carboxy-terminus. The transmembrane domain of the M2 protein forms the channel pore. The M2 protein, which forms a homotetramer, has H ion channel which was found to be regulated by pH []and may have a pivotal role in the biology of Influenza virus infection [].
This entry represents a family of nucleoside-triphosphatases which have activity towards ATP, GTP, CTP, TTP and UTP and may hydrolyse nucleoside diphosphates with lower efficiency []. It includes proteins from bacteria to human, and the function was determined first in a hyperthermophilic bacterium to be an NTPase []. The structure of one member-sequence represents a variation of the RecA fold, and implies that the function might be that of a DNA/RNA modifying enzyme []. The sequence carries both a Walker A and Walker B motif which together are characteristic of ATPases or GTPases. The protein exhibits an increased expression profile in human liver cholangiocarcinoma when compared to normal tissue [].
Centromere protein W (CENP-W) is a component of the CENPA-NAC (nucleosome-associated) complex, which plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation []. CENP-W gene is up-regulated in various types of cancers and was first identified as a putative oncogene, CUG2 []. It can be regulated by CSN5, a component of the CSN complex involved in protein degradation via the ubiquitin-proteasome pathway []. The DNA-binding regions in CENP-T or CENP-W is essential for inducing positive supercoils into DNA and for the kinetochore targeting of the CENP-T-W-S-X complex [].
DNA polymerase epsilon is essential for cell viability and chromosomal DNA replication in budding yeast. In addition, DNA polymerase epsilon may be involved in DNA repair and cell-cycle checkpoint control. The enzyme consists of at least four subunits in mammalian cells as well as in yeast. The largest subunit of DNA polymerase epsilon is responsible for polymerase activity. In mouse, the DNA polymerase epsilon subunit B is the second largest subunit of the DNA polymerase. A part of the N-terminal was found to be responsible for the interaction with SAP18. Experimental evidence suggests that this subunit may recruit histone deacetylase to the replication fork to modify the chromatin structure [].
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. Whereas hsClp1 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, a C-terminal domain containing a novel alpha/β-fold and a central domain that binds ATP [, ]. This entry represents the N-terminal domain involved in DNA binding [].
The neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFamide) is a potent cardioactive neuropeptide in Lymnaea stagnalis []. FMRFamide (Phe-Met-Arg-Phe-NH2) was first demonstrated to be cardioactive in several molluscan species. FMRFamide is now known to be cardioexcitatory in mammals, to inhibit morphine-induced antinociception, and to block morphine-, defeat-, and deprivation-induced feeding []. Thirteen neuropeptides varying in length from 7 to 11 residues and ending C-terminally in -Phe-Met-Arg-Phe-NH2 (calliFMRFamides 1-13) and one dodecapeptide ending in -Met-Ile-Arg-Phe-NH2 (calliMIRFamide 1) have been isolated from thoracic ganglia of the blowfly Calliphora vomitoria. Results indicate that the N terminus (in addition to the C terminus as previously found for FMRFamides of other organisms) is crucial for at least some biological activities [].
This family was recently identified as belonging to the nucleotidyltransferase superfamily []. AbiEii is the cognate toxin of the type IV toxin-antitoxin 'innate immunity' bacterial abortive infection (Abi) system that protects bacteria from the spread of a phage infection. The Abi system is activated upon infection with phage to abort the cell thus preventing the spread of phage through viral replication. There are some 20 or more Abis, and they are predominantly plasmid-encoded lactococcal systems. TA, toxin-antitoxin, systems on plasmids function by killing cells that lose the plasmid upon division. AbiE phage resistance systems function as novel Type IV TAs and are widespread in bacteria and archaea. The cognate antitoxin is [].
TRBP2 was first identified as a HIV-1 TAR RNA-binding protein []. TRBP2 is a component of the RISC loading complex (RLC), which functions in RNA-mediated gene silencing (RNAi). It is a double-stranded RNA (dsRNA)-binding protein that associates with endonuclease Dicer, which cleaves precursor RNA molecules to produce microRNAs (miRNAs) and short interfering RNAs (siRNAs) in RNAi pathway []. Together with another dsRNA-binding protein, PACT, they function as key regulators of miRNA and siRNA biogenesis by Dicer in substrate recognition, binding, processing and RISC loading []. TRBP2 contains three double-stranded RNA binding motifs (DSRMs). This entry represents the first DSRM of TRBP2.
TRBP2 was first identified as a HIV-1 TAR RNA-binding protein []. TRBP2 is a component of the RISC loading complex (RLC), which functions in RNA-mediated gene silencing (RNAi). It is a double-stranded RNA (dsRNA)-binding protein that associates with endonuclease Dicer, which cleaves precursor RNA molecules to produce microRNAs (miRNAs) and short interfering RNAs (siRNAs) in RNAi pathway []. Together with another dsRNA-binding protein, PACT, they function as key regulators of miRNA and siRNA biogenesis by Dicer in substrate recognition, binding, processing and RISC loading []. TRBP2 contains three double-stranded RNA binding motifs (DSRMs). This entry represents the second DSRM of TRBP2.
TRBP2 was first identified as a HIV-1 TAR RNA-binding protein []. TRBP2 is a component of the RISC loading complex (RLC), which functions in RNA-mediated gene silencing (RNAi). It is a double-stranded RNA (dsRNA)-binding protein that associates with endonuclease Dicer, which cleaves precursor RNA molecules to produce microRNAs (miRNAs) and short interfering RNAs (siRNAs) in RNAi pathway []. Together with another dsRNA-binding protein, PACT, they function as key regulators of miRNA and siRNA biogenesis by Dicer in substrate recognition, binding, processing and RISC loading []. TRBP2 contains three double-stranded RNA binding motifs (DSRMs). This entry represents the third DSRM of TRBP2.
Hid-1 (high-temperature-induced dauer-formation protein 1) was originally identified as a Caenorhabditis elegans gene encoding a protein that regulates larval development []. HID-1 is conserved from fungi to humans. It contains up to seven potential transmembrane domains separated by regions of low complexity. It may control the correct sorting of DCV (dense core vesicle, also known as the secretory granule) cargoes in the Golgi apparatus []. Mammalian HID-1 localized to the medial- and trans- Golgi apparatus as well as the cytosol and may be involved in the intracellular trafficking within the Golgi region [].This entry also includes Ecm30 from budding yeasts. The function of Ecm30 is not clear.
This entry represents the protein strawberry notch homologue 2 (SBNO2) from vertebrates. It may be a component of the pathways that contribute to the downstream anti-inflammatory effects of IL-10 []. The genetic variations in the SBNO2 gene have been linked to susceptibility to Crohn's disease, a type of inflammatory bowel disease (IBD) that may affect any part of the gastrointestinal tract from mouth to anus [].Strawberry notch proteins carry DExD/H-box groups and helicase C-terminal domains. These proteins promote the expression of diverse targets, potentially through interactions with transcriptional activator or repressor complexes []. Strawberry notch was first identified in Drosophila where functions downstream of Notch and regulates gene expression during development [, ].
Hepatitis B X-interacting protein (HBXIP, also known as LAMTOR5) was originally recognised for its association with the X protein of hepatitis B virus (HBV) and ability to down-regulate HBV replication []. When complexed to the anti-apoptotic protein survivin, HBXIP interferes with apoptosome assembly, preventing recruitment of pro-caspase-9 to oligomerised APAF1, thereby selectively suppressing apoptosis initiated via the mitochondrial/cytochrome c pathway []. HBXIP is one of the Ragulator components that are required for mTORC1 activation by amino acids []. It is also part of the AA (amino acid) sensing machinery in human CD4+ T cells [].
