ABC transporter, urea utilisation-associated, substrate-binding protein
Type:
Family
Description:
This entry consists of ABC transporter substrate-binding proteins associated with the urea carboxylase/allophanate hydrolase pathway, an alternative to urease for urea degradation. These proteins are specific to bacteria with the urea degradation pathway and are encoded close to the urea carboxylase and allophanate hydrolase genes. The substrate for this transporter is therefore likely to be urea or a compound from which urea is easily derived.
This entry represents the PA domain found in transferrin receptor proteins 1 (TfR1) and 2 (TfR2). The function of the PA domain is not clear.The transferrin receptor 1 (TfR) is a transmembrane protein that assists iron uptake into vertebrate cells through a cycle of endo- and exocytosis of the iron transport protein transferrin (Tf). TfR binds iron-loaded (diferric) Tf at the cell surface and carries it to the endosome, where the iron dissociates from Tf. The apo-Tf remains bound to TfR until it reaches the cell surface, where apo-Tf is replaced by diferric Tf from the serum to begin the cycle again. The crystal structure of a TfR monomer reveals a 3-domain structure: a protease-like domain that closely resembles carboxy- and amino-peptidases; an apical domain consisting of a β-sandwich; and a helical dimerisation domain. The dimerisation domain consists of a 4-helical bundle that makes contact with each of the three domains in the dimer partner [
].In humans, TfR is a homodimeric type II transmembrane protein highly expressed on brain endothelial cells. It may undergo transcytosis at the blood-brain barrier (BBB) to allow entry of iron-bound Transferrin by constitutive endocytosis [
]. The TfR-facilitated transcytosis has been explored to deliver therapeutics into the brain in a noninvasive manner [,
].
The HutP protein regulates the expression of Bacillus 'hut' structural genes by an anti-termination complex, which recognises three UAG triplet units, separated by four non-conserved nucleotides on the RNA terminator region. L-Histidine and Mg2+ ions are also required. These proteins exhibit the structural elements of alpha/beta proteins, arranged in the order: α-α-beta-α-α-β-β-beta in the primary structure, and the four antiparallel β-strands form a β-sheet in the order beta1-beta2-beta3-beta4, with two α-helices each on the front (alpha1 and alpha2) and at the back (alpha3 and alpha4) of the β-sheet [
].
Mesoderm induction early response protein/metastasis-associated protein
Type:
Family
Description:
MTA (metastasis-associated) proteins, including MTA1-3, are transcriptional co-repressors that function in histone deacetylation and are involved in the NuRD complex. Nevertheless, MTA1 and MTA2 have been shown to deacetylate non-histone proteins, such as p53. The expression of MTA proteins have been linked to human cancers [
].Mesoderm induction early response proteins (MIER1-3) are ELM2-SANT domain-containing proteins. MIER1 functions as a transcriptional repressor through its ability to recruit HDAC1/2 activity[
]. The function of MIER2 and MIER3 is not clear [].
Complex I intermediate-associated protein 30, mitochondrial
Type:
Family
Description:
Mitochondrial complex I intermediate-associated protein 30 (CIA30) is present in human and mouse, and also in Schizosaccharomyces pombe (Fission yeast) which does not contain the NADH dehydrogenase component of complex I, or many of the other essential subunits. This means it is not directly involved in oxidative phosphorylation [
,
]. In Drosophila it has been shown to be a chaperone required for assembly complex I [].
This entry represents a group of plant proteins, including glycine-rich cell wall structural protein 1/2 (GRP1/2) from rice. Their function is not clear.
This superfamily represent the C-terminal domain of the MAP kinase activated protein kinases (MAPKAPKs). Proteins containing this domain include Mapkapk2 and Mapkapk3. They are mainly involved in post-transcriptional regulation of gene expression and play an role in inflammation and cancer [
].
Urease accessory protein UreH-like, transmembrane domain
Type:
Domain
Description:
Urease is a nickel containing metalloenzyme that hydrolyses urea into ammonia [
]. This entry represents a transmembrane domain found in UreH, an urease accessory protein []. In Helicobacter pylori, UreH is part of the UreG/UreF/UreH complex that may be responsible for delivery of nickel ions into the urease active site [].This entry also includes Chloroplast protein FOR GROWTH AND FERTILITY 1/2 from Arabidopsis, transmembrane proteins essential for supporting female gametogenesis and embryogenesis, probably by securing local energy supply [
].
Required for excision 1-B domain-containing protein
Type:
Family
Description:
This family of proteins includes Chlamydomonas reinhardtii REX1-B (Required for Excision 1-B) which is involved in a light-independent DNA repair pathway [
]. It also includes REX1-B domain-containing protein from mammals, whose function is not known.
Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1, PANDER-like domain
Type:
Domain
Description:
O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) participates in O-mannosyl glycosylation and may be responsible for creating GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr moieties on alpha dystroglycan and other O-mannosylated proteins [
,
]. POMGnT1 consists of a stem domain, a catalytic domain, and an extended linker region connecting the two domains. The fold of the stem domain resembles that of PANDER (pancreatic-derived factor); a protein involved in the regulation of glucose homeostasis, but whose the molecular function has not been determined [].
This entry represents the FYVE-related domain of Spire homolog 1 (Spir-1) and similar proteins from chordates. Spir-1 acts as an actin nucleation factor that remain associated with the slow-growing pointed end of the new filament [
,
]. It is involved in intracellular vesicle transport along actin fibres, providing a novel link between actin cytoskeleton dynamics and intracellular transport []. The structure of Spire has been revealed [,
]. It contains an N-terminal KIND (kinase noncatalytic C-lobe) domain and four actin-binding WH2 (WASP homology 2) domains, a Rab GTPase-interaction Spir-box, and a C-terminal FYVE zinc-binding domain (this entry) []. The mammalian genome encodes two Spir proteins, Spir-1 and Spir-2. In adult tissues, the spir-2 gene shows a rather broad expression pattern, whereas spir-1 is mainly expressed in neuronal cells of the nervous system. Spir-1 may have a role in neural function [
].
Nitrogenase MoFe cofactor biosynthesis protein NifE
Type:
Family
Description:
The enzyme responsible for nitrogen fixation, the nitrogenase, shows a high degree of conservation of structure, function, and amino acid sequence across wide phylogenetic ranges. All known Mo-nitrogenases consist of two components, component I (also called dinitrogenase, or Fe-Mo protein), an alpha2beta2 tetramer encoded by the nifD and nifK genes, and component II (dinitrogenase reductase, or Fe protein) a homodimer encoded by the nifH gene [
,
] which has an Fe4S4 cluster bound between the subunits and two ATP-binding domains. The Fe protein supplies energy by ATP hydrolysis, and transfers electrons from reduced ferredoxin or flavodoxin to component 1 for the reduction of molecular nitrogen to ammonia [,
]. Nitrogenase contains two unusual rare metal clusters; one of them is the iron molybdenum cofactor (FeMo-co), which is considered to be the site of dinitrogen reduction and whose biosynthesis requires the products of the nifNE operon and of some other nif genes []. It has been proposed that nifNE might serve as a scaffold upon which FeMo-co is built and then inserted into component I [].This entry refers to the nitrogenase MoFe cofactor biosynthesis protein encoded by the gene nifE.
Members of this family, designated S-layer assembly protein (SlaP), occur next to a Bacillus anthracis-type accessory Sec system SecA2. Members have two tandem copies of a duplicated SLAP domain (
) that may also occur in other contexts. SlaP is found both free in the cytoplasm and membrane-associated. SecA2 and SlaP appear to work together to modify Sec for efficient S-layer secretion [
].
Probable phospholipid ABC transporter-binding protein MlaD
Type:
Family
Description:
Members of this protein family are the intermembrane phospholipid transport system binding protein MlaD (maintenance of Lipid Asymmetry D) of an ABC transport system that removes phospholipid from the outer leaflet of the Gram-negative bacterial outer membrane (OM), leaving only lipopolysaccharide in the outer leaflet. The Mla locus has long been associated with toluene tolerance, consistent with the proposed role in retrograde transport of phospholipid and therefore with maintaining the integrity of the OM as a protective barrier [
]. MlaD forms extremely stable hexamers within the complex, functions in substrate binding with strong affinity for phospholipids, and modulates ATP hydrolytic activity [].
RUFY4 contains an N-terminal RUN domain and a C-terminal FYVE domain. It is a positive molecular regulator of macroautophagy in primary dendritic cells (DCs) [
].
Members of this family are core structural proteins found in the double-stranded RNA virus Phytoreovirus. They are large proteins without apparent domain division, with a number of all-alpha regions and one all beta domain near the C-terminal end [
].
Energy-coupling factor transporter ATP-binding protein EcfA1
Type:
Family
Description:
EcfA1 is an ATP-binding (A) component of a common energy-coupling factor (ECF) transport systems [
]. It shares homology with the ATP-binding cassette (ABC) protein [].ECF transporters usually contain two ATPase subunits (or a double-length fusion protein), a T component, and a substrate capture (S) component that is highly variable, and may be interchangeable in genomes with only one T component.
ECF transporters can be classified into two groups: group I includes transporters that have a dedicated AT module encoded in the same gene cluster as an S component, while group II employs a universal energy-coupling module (EcfAA'T) that is encoded by a separate gene cassette and shared by many different unlinked S components. Group II is ubiquitous in the phyla Firmicutes and Thermotogales and also occurs in some members of the Archaea [].
Energy-coupling factor transporter ATP-binding protein EcfA2
Type:
Family
Description:
EcfA2 is an ATP-binding (A) component of a common energy-coupling factor (ECF) transport systems [
]. It shares homology with the ATP-binding cassette (ABC) protein [].ECF transporters usually contain two ATPase subunits (or a double-length fusion protein), a T component, and a substrate capture (S) component that is highly variable, and may be interchangeable in genomes with only one T component.
ECF transporters can be classified into two groups: group I includes transporters that have a dedicated AT module encoded in the same gene cluster as an S component, while group II employs a universal energy-coupling module (EcfAA'T) that is encoded by a separate gene cassette and shared by many different unlinked S components. Group II is ubiquitous in the phyla Firmicutes and Thermotogales and also occurs in some members of the Archaea [].
Nonstructural protein 10, zinc-binding domain, arterivirus
Type:
Domain
Description:
Nidoviruses (Coronaviridae, Arteriviridae, and Roniviridae) feature the most complex genetic organization among plus-strand RNA viruses. Their
replicase genes encode an exceptionally large number of nonstructural protein domains which mediate the key functions required for genomic RNA synthesis (replication) and subgenomic RNA (sgRNA) synthesis (transcription). They encode a nonstructural protein, called NSP10 in arteriviruses (Av) and NSP13 in coronaviruses (CoV) [], that is comprised of a C-terminal nucleoside triphosphate-binding/helicase (Hel) motif and a N-terminal cysteine-rich zinc-binding domain (ZBD). The ZBD is critically involved in nidovirus replication and transcription, modulating the ATPase/helicase activity in cis [,
,
,
]. In SARS-CoV, it has been shown that NSP12 directly interacts with NSP13 and enhances its helicase activity [,
,
,
].The ZBD is comprised of about 80 to 100 residues, including 12 to 13 conserved Cys/His residues. It consists of a RING-like module and treble-cleft zinc finger, together coordinating three Zn atoms. The N-terminal RING-like module has a notable binuclear structure with a cross-brace topology involving 6 Cys and 2 His residues that coordinate two zinc ions. The C-terminal zinc finger of ZBD adopts a treble-cleft fold distinct from that of
the RING module. It coordinates one Zn ion with a C[H/C]C[C/H] pattern [].This entry represents the ZBD domain from NSP10 of arteriviruses.
Zinc finger MYND domain-containing protein 15 (ZMYND150 is a histone deacetylase-dependent transcriptional repressor that plays a role in spermiogenesis [
]. Mutations of the ZMYND15 gene have been linked to azoospermia [].
Proteins in this entry contain WD40 repeats. This entry includes mammalian EARP and GARP complex-interacting protein 1 (EIPR1 or TSSC1), which is a component of the endosomal retrieval machinery, binding to both the tethering complexes GARP and EARP. GARP participates in SNARE-dependent fusion of endosome-derived carriers with the trans-Golgi network, wheras EARP does the same for recycling endosomes [
]. Also included in this family is the EARP-interacting protein 1 from the nematode Caenorhabditis elegans, which trafficks cargo to the dense-core vesicle, a secretory organelle that mediates the regulated release of peptide hormones, growth factors, and biogenic amines and which originates from the trans-Golgi of neurons and neuroendocrine cells [
]. The WD repeat-containing protein DWA2 from Arabidopsis thaliana is also a member of this family. DWA2 is a component of an E3 ubiquitin-protein ligase complex that acts as negative regulator in abscisic acid signaling [].
RING finger protein 11 (RNF11) is an E3 ubiquitin-protein ligase that acts both as an adaptor and a modulator of itch-mediated control of ubiquitination events underlying membrane traffic. It is the downstream of an enzymatic cascade for the ubiquitination of specific substrates. It is also a molecular adaptor of homologous to E6-associated protein C terminus (HECT)-type ligases [
]. RNF11 has been implicated in the regulation of several signaling pathways. It enhances the transforming growth factor receptor (TGFR) signaling by both abrogating Smurf2-mediated receptor ubiquitination and by promoting the Smurf2-mediated degradation of AMSH (associated molecule with the SH3 domain of STAM), a de-ubiquitinating enzyme that enhances transforming growth factor-beta (TGF-beta) signalling and epidermal growth factor receptor (EGFR) endosomal recycling [
,
]. It also acts directly on Smad4 to enhance Smad4 function, and plays a role in prolonged TGF-beta signalling []. Moreover, RNF11 functions as a critical component of the A20 ubiquitin-editing protein complex that negatively regulates tumor necrosis factor (TNF)-mediated nuclear factor (NF)-kappaB activation []. It also interacts with Smad anchor for receptor activation (SARA) and the endosomal sorting complex required for transport (ESCRT)-0 complex, thus participating in the regulation of lysosomal degradation of EGFR []. Furthermore, RNF11 acts as a novel GGA cargo actively participating in regulating the ubiquitination of the GGA protein family []. In addition, RNF11 functions together with TAX1BP1 to target TANK-binding kinase 1 (TBK1)/IkappaB kinase IKKi, and further restricts antiviral signaling and type I interferon (IFN)-beta production []. RNF11 contains an N-terminal PPPY motif that binds WW domain-containing proteins such as AIP4/itch, Nedd4 and Smurf1/2 (SMAD-specific E3 ubiquitin-protein ligase 1/2), and a C-terminal C3H2C3-type RING-H2 finger that functions as a scaffold for the coordinated transfer of ubiquitin to substrate proteins together with the E2 enzymes UbcH527 and Ubc13.
Thiosulfate oxidation carrier complex protein SoxZ
Type:
Family
Description:
SoxZ forms a heterodimer with SoxY, the subunit that forms a covalent bond with a sulfur moiety during thiosulfate oxidation to sulfate [
]. Note that virtually all proteins that have a SoxY domain fused to a SoxZ domain are functionally distinct and not involved in thiosulfate oxidation.
Transmembrane and ubiquitin-like domain-containing protein 1/2
Type:
Family
Description:
The entry includes proteins with ubiquitin-like domains. Transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1) is involved in the sterol-regulated ubiquitination and degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase by the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway. TMUB1 and SPFH2 associate with mammalian gp78, the membrane-bound ubiquitin ligase in the ERAD pathway [
].
DENN domain-containing protein 5A/B, PLAT/LH2 domain
Type:
Domain
Description:
This entry represents the PLAT/LH2 domain of DENN domain-containing proteins 5A/B (DEN5A/B) and similar animal proteins that belong to the RAB6 interacting protein 1 (Rab6IP1) family. PLAT/LH2 domains consist of an eight stranded β-barrel. In RabIP1, this domain may participate in lipid-mediated modulation of Rab6IP1's function via its generally proposed function of mediating interaction with lipids or membrane bound proteins [
,
].This entry includes DENN domain-containing proteins 5A/B (DEN5A/B) from humans and similar animal proteins that belong to the RAB6 interacting protein 1 (Rab6IP1) family. DEN5A/B are guanine nucleotide exchange factors (GEFs) which may activate RAB6A and RAB39A and/or RAB39B. They promote the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form [
]. DEN5A is involved in the negative regulation of neurite outgrowth [].
Conjugal transfer/type IV secretion protein DotA/TraY
Type:
Family
Description:
Members of this protein family include transfer protein TraY of IncI1 plasmid R64 and DotA (defect in organelle trafficking A) of Legionella pneumophila [
,
].
The function of ZNHIT2 is not known. Homologues are known from animals, plants and fungi, and each contains a HIT-type zinc finger. The human gene (also known as C11orf5) is part of the FAUNA cluster, and is highly expressed in the testis, particularly the lumen of seminiferous tubules, suggesting it is highly expressed in germ cells of different developmental stages [
].
Endoplasmic reticulum membrane-associated RNA degradation protein
Type:
Family
Description:
ERMARD (endoplasmic reticulum membrane-associated RNA degradation) is a multi-pass membrane protein that may play a role in neuronal migration during embryonic development [
].
This is an α-helical domain that is usually N-terminal to a metallopeptidase domain. The domain is found in both in polyvalent proteins of conjugative elements and phages/prophages [
].
U11/U12 small nuclear ribonucleoprotein 25kDa protein
Type:
Family
Description:
U11 and U12 small nuclear ribonucleoprotein (snRNPs) bind U12-type pre-mRNAs as a preformed di-snRNP complex, simultaneously recognizing the 5' splice site and branchpoint sequence. SNRNP25 is a component of the U11/U12 snRNP complex [
,
]. Homologues are known from animals, plants and fungi.
Zinc finger CCCH domain-containing proteins A (ZC3H7A) and B (ZC3H7B) bind to microRNAs MIR7-1, MIR16-2 and MIR29A hairpins recognizing the 3'-ATA(A/T)-5' motif in the apical loop [
]. Homologues are known from animals.
This is a predicted enzymatic alpha and beta fold domain with a large, prominent helix with conserved glutamate residue and several additional conserved residues including the motifs HTxN and SN [
]. The domain is associated with polyvalent proteins of firmicute conjugative elements [].
Three cysteine-rich proteins (also believed to be lipoproteins) make up the
extracellular matrix of the Chlamydial outer membrane []. They are involved in the essential structural integrity of both the elementary body (EB) and
recticulate body (RB) phase. As these bacteria lack the peptidoglycan layercommon to most Gram-negative microbes, such proteins are highly important
in the pathogenicity of the organism.The largest of these is the major outer membrane protein (MOMP), and
constitutes around 60% of the total protein for the membrane []. OMP2is the second largest, with a molecular mass of 58kDa, while the OMP3
protein is ~15kDa []. MOMP is believed to elicit the strongest immune response, and has recently been linked to heart disease through its sequence
similarity to a murine heart-muscle specific alpha myosin [].The OMP3 family plays a structural role in the outer membrane during
the EB stage of the Chlamydial cell, and different biovars show a small, yet highly significant, change at peptide charge level [
]. Members of this family include Chlamydia trachomatis, Chlamydia pneumoniae, and Chlamydia psittaci.
Three cysteine-rich proteins (also believed to be lipoproteins) make up the
extracellular matrix of the Chlamydial outer membrane []. They are involved in the essential structural integrity of both the elementary body (EB) and recticulate body (RB) phase. As these bacteria lack the peptidoglycan layer common to most Gram-negative microbes, such proteins are highly important in the pathogenicity of the organism.
The largest of these is the major outer membrane protein (MOMP), and
constitutes around 60% of the total protein for the membrane []. OMP6 is the second largest, with a molecular mass of 58kDa, while the OMP3 protein is ~15kDa []. MOMP is believed to elicit the strongest immune response, and has recently been linked to heart disease through its sequence similarity to a murine heart-muscle specific alpha myosin [].The OMP6 family plays a structural role in the outer membrane during
the EB stage of the Chlamydial cell, and different biovars show a small, yet highly significant, change at peptide charge level [
]. Members of this family include Chlamydia trachomatis, Chlamydia pneumoniae and Chlamydia psittaci.
This entry represents the N-terminal domain of dynein regulatory complex protein 1/2 (DRC1/2). DRC1 is a key component of the nexin-dynein regulatory complex (N-DRC), essential for N-DRC integrity. It is required for the assembly and regulation of specific classes of inner dynein arm motors. It may also function to restrict dynein-driven microtubule sliding, thus aiding in the generation of ciliary bending [
]. Mutations of DRC1 gene cause Ciliary dyskinesia, primary, 21 (CILD21), which is a disorder characterised by abnormalities of motile cilia [
]. DRC2, also known as CCDC65, is an essential component of the nexin-dynein regulatory complex [
].
Mitochondrial distribution and morphology protein 12
Type:
Family
Description:
Mitochondrial distribution and morphology protein 12 (Mdm12) is a component of the ERMES/MDM complex (composed of MMM1, MDM10, MDM12 and MDM34), which serves as a molecular tether to connect the endoplasmic reticulum and mitochondria. Mdm12 is required for the interaction of the ER-resident membrane protein Mmm1 and the outer mitochondrial membrane-resident β-barrel protein Mdm10 [
]. The Mdm12-Mmm1 subcomplex functions in the biogenesis of all mitochondrial outer membrane β-barrel proteins, and acts in a late step after the SAM (sorting and assembly machinery) complex. The Mdm10-Mdm12-Mmm1 subcomplex further acts in the Tom40 (translocase of outer membrane 40)-specific pathway after the action of the Mdm12-Mmm1 complex. Mdm12 is essential for establishing and maintaining the structure of mitochondria and maintenance of mtDNA nucleoids [,
].
Maintenance of mitochondrial morphology protein 1 (Mmm1) is a component of the ERMES/MDM complex (composed of MMM1, MDM10, MDM12 and MDM34), which serves as a molecular tether to connect the endoplasmic reticulum and mitochondria. The MDM12-MMM1 subcomplex functions in biogenesis of all outer membrane β-barrel proteins, and acts in a late step after the SAM (sorting and assembly machinery) complex [
]. The MDM10-MDM12-MMM1 subcomplex further acts in the TOM40 (translocase of outer membrane 40)-specific pathway after the action of the MDM12-MMM1 complex [,
,
].
Mitochondrial distribution and morphology protein 34
Type:
Family
Description:
Mitochondrial distribution and morphology protein 34 (Mdm34) is a component of the ERMES/MDM complex, which serves as a molecular tether to connect the endoplasmic reticulum and mitochondria. MDM34 is required for the interaction of the ER-resident membrane protein MMM1 and the outer mitochondrial membrane-resident β-barrel protein MDM10 [
,
,
].
Mitochondrial distribution and morphology protein 10
Type:
Family
Description:
Mitochondrial distribution and morphology protein 10 (Mdm10) is a component of the ERMES/MDM complex (composed of MMM1, MDM10, MDM12 and MDM34), which serves as a molecular tether to connect the endoplasmic reticulum and mitochondria. MDM10 is involved in the late assembly steps of the general translocase of the mitochondrial outer membrane (TOM complex) [
]. It functions in the TOM40-specific route of the assembly of outer membrane β-barrel proteins, including the association of TOM40 with the receptor TOM22 and small TOM proteins [,
].
Synaptonemal complex protein 2, Spt16M-like domain
Type:
Domain
Description:
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 SLD structure is highly similar to the middle domain of the histone chaperone FACT. It consists of a twisted ten-stranded β-sheet flanked by two helices. Since the SLD domain structurally resembles Spt16M, which is known as the well-recognized histone protein H2A-H2B; it is speculated that the SLD subdomain may be involved in chromatin binding [
].
This SPRY domain is found at the N terminus of RING finger protein 123 (also known as E3 ubiquitin-protein ligase RNF123, KPC1). The ring finger domain motif is present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. RNF123 displays E3 ubiquitin ligase activity toward the cyclin-dependent kinase inhibitor p27 (Kip1) [
] and p105 and inhibits tumor growth via regulation of p50-dependent tumor suppressor genes [].Proteins containing this domain also include AtKPC1 from Arabidopsis. AtKPC1 is an E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of KRP1 and KRP2 [
,
].
This SPRY domain is found in Ran binding protein M (RanBPM, also known as RanBP9) and RanBP10. RanBPM and RanBP10 are non-canonical members of the Ran binding protein family that lack the Ran binding domain and do not associate with Ran GTPase in vivo. RanBPM is a scaffolding protein important for a variety of cellular processes [
,
]. RanBP10 has been shown to function as a cytosolic guanine exchange factor and microtubule regulator [,
]. Both of these proteins contain a SPRY domain, which has been implicated in mediating protein-protein interactions with a variety of targets, including the DEAD-box containing ATP-dependent RNA helicase (DDX-4) [,
,
].
This is a beta strand rich domain that lacks strongly conserved polar residues [
]. It is fast diverging and is found in polyvalent proteins of conjugative elements [].
CUEDC2 is a novel negative regulator of progesterone receptor (PR) and functions to promote the progesterone-induced PR degradation by the ubiquitin-proteasome pathway [
]. It also acts as the regulator of JAK1/STAT3 signaling through inhibiting cytokine-induced phosphorylation of JAK1 and STAT3 and the subsequent STAT3 transcriptional activity []. This entry represents the CUE domain found in CUEDC2.
CRISPR-associated protein Cas8a1/Csx13, Myxan subtype, C-terminal
Type:
Domain
Description:
Members of the Myxococcus xanthus subtype of the Cas8a1/Csx13 family are found among cas (CRISPR-Associated) genes close to CRISPR repeats in Leptospira interrogans (a spirochete), Myxococcus xanthus (a delta-proteobacterium), and Lyngbya sp. PCC 8106 (a cyanobacterium). They are found with other cas genes in Anabaena variabilis ATCC 29413. In Myxococcus xanthus Cas8a1 is also known as DevT (developmental protein T) where stimulates synthesis of a signal transduction protein required for fruiting body morphogenesis (formation of fruiting bodies within the rod-shaped cells under starvation conditions that differentiate into spherical spores) [
,
].This entry corresponds to the C-terminal domain of the proteins; the N-terminal domain is described by
. In Lyngbya sp., the protein is split into two tandem genes, and this entry corresponds to the downstream gene in these species.
This entry includes N-terminal EF-hand calcium binding proteins 1, 2 and 3 (NECAB1, NECAB2 and NECAB3). They are expressed in the adult mouse hippocampus and dentate gyrus [
] and in the rat/human spinal cord []. NECAB2 has been shown to bind to the adenosine A(2A) receptor [] and the mGlu(5) receptor []. NECAB3 has been shown to regulate HIF-1 (hypoxia inducible factor-1) activity via Mint3 in cancer cells [].
ER membrane protein complex subunit 2 (EMC2, also known as tetratricopeptide repeat protein 35) is a tetratricopeptide repeat-containing protein, and a component of the ER membrane protein complex (EMC), which is required for efficient folding of proteins in the endoplasmic reticulum (ER) [
]. This entry also includes TPR repeat protein Oca3 from the fission yeast Schizosaccharomyces pombe which may be involved in cell cycle regulation [].
Bacteriophage DNA replication protein Gp16.7 superfamily
Type:
Homologous_superfamily
Description:
The early-expressed gene 16.7 is conserved in bacteriophage phi-29 and related phages. It encodes a membrane protein, GP16.7, consisting of an N-terminal transmembrane domain and a C-terminal DNA-binding and dimerisation domain. GP16.7 plays an important role in organising membrane-associated bacteriophage DNA replication [
, ]. The C-terminal domain has a similar secondary structure similar to homeodomains, but forms a fundamentally different tertiary structure consisting of a six-helical dimeric fold []. Multimerisation of this dimer leads to efficient DNA binding.
This is a predicted enzymatic α-helical domain with highly conserved aspartate residues [
]. The domain is found in polyvalent proteins of phage and prophage genes and is often the immediate neighbour of a lysozyme gene [].
The connexins are a family of integral membrane proteins that oligomerise to form intercellular channels that are clustered at gap junctions. These channels are specialised sites of cell-cell contact that allow the passage of ions, intracellular metabolites and messenger molecules (with molecular weight less than 1-2kDa) from the cytoplasm of one cell to its opposing neighbours. They are found in almost all vertebrate cell types, and somewhat similar proteins have been cloned from plant species. Invertebrates utilise a different family of molecules, innexins, that share a similar predicted secondary structure to the vertebrate connexins, but have no sequence identity to them [].Vertebrate gap junction channels are thought to participate in diverse biological functions. For instance, in the heart they permit the rapid cell-cell transfer of action potentials, ensuring coordinated contraction of the cardiomyocytes. They are also responsible for neurotransmission at specialised 'electrical' synapses. In non-excitable tissues, such as the liver, they may allow metabolic cooperation between cells. In the brain, glial cells are extensively-coupled by gap junctions; this allows waves of intracellular Ca
2+to propagate through nervous tissue, and may contribute to their ability to spatially-buffer local changes in extracellular K
+concentration [
].The connexin protein family is encoded by at least 13 genes in rodents, with many homologues cloned from other species. They show overlapping tissue expression patterns, most tissues expressing more than one connexin type. Their conductances, permeability to different molecules, phosphorylation and voltage-dependence of their gating, have been found to vary. Possible communication diversity is increased further by the fact that gap junctions may be formed by the association of different connexin isoforms from apposing cells. However, in vitro studies have shown that not all possible combinations of connexins produce active channels [
,
].Hydropathy analysis predicts that all cloned connexins share a common transmembrane (TM) topology. Each connexin is thought to contain 4 TM
domains, with two extracellular and three cytoplasmic regions. This modelhas been validated for several of the family members by
in vitrobiochemical
analysis. Both N- and C-termini are thought to face the cytoplasm, and thethird TM domain has an amphipathic character, suggesting that it contributes
to the lining of the formed-channel. Amino acid sequence identity betweenthe isoforms is ~50-80%, with the TM domains being well conserved. Both
extracellular loops contain characteristically conserved cysteine residues,which likely form intramolecular disulphide bonds. By contrast, the single
putative intracellular loop (between TM domains 2 and 3) and the cytoplasmicC terminus are highly variable among the family members.
Six connexins arethought to associate to form a hemi-channel, or connexon. Two connexons then
interact (likely via the extracellular loops of their connexins) to form thecomplete gap junction channel.
NH2-*** *** *************-COOH** ** ** **
** ** ** ** Cytoplasmic---**----**-----**----**----------------
** ** ** ** Membrane** ** ** **
---**----**-----**----**----------------** ** ** ** Extracellular
** ** ** **** **
Two sets of nomenclature have been used to identify the connexins. The
first, and most commonly used, classifies the connexin molecules accordingto molecular weight, such as connexin43 (abbreviated to Cx43), indicating
a connexin of molecular weight close to 43kDa. However, studies haverevealed cases where clear functional homologues exist across species
that have quite different molecular masses; therefore, an alternativenomenclature was proposed based on evolutionary considerations, which
divides the family into two major subclasses, alpha and beta, each with anumber of members [
]. Due to their ubiquity and overlapping tissue distributions, it has proved difficult to elucidate the functions of individual connexin isoforms. To circumvent this problem, particular connexin-encoding genes have been subjected to targeted-disruption in mice, and the phenotype of the resulting animals investigated. Around half the connexin isoforms have been investigated in this manner []. Further insight into the functional roles of connexins has come from the discovery that a number of human diseases are caused by mutations in connexin genes. For instance, mutations in Cx32 give rise to a form of inherited peripheral neuropathy called X-linked dominant Charcot-Marie-Tooth disease []. Similarly, mutations in Cx26 are responsible for both autosomal recessive and dominant forms of nonsyndromic deafness, a disorder characterised by hearing loss, with no apparent effects on other organ systems.Gap junction alpha-1 protein (also called connexin43, or Cx43) is a connexin
of 381 amino acid residues (human isoform) that is widely expressed inseveral organs and cell types, and is the principal gap junction protein of
the heart. Characterisation of genetically-engineered mice that lack Cx43,and also of human patients that have spontaneously-occurring mutations in
the gene encoding it (GJA1), suggest Cx43 is essential for the developmentof normal cardiac architecture and ventricular conduction. Mice lacking Cx43
survive to term but die shortly after birth. They have cardiac malformationsthat lead to the obstruction of the pulmonary artery, leading to neonatal
cyanosis, and subsequent death. This phenotype is reminiscent of some formsof stenosis of the pulmonary artery. Human subjects with visceroatrial
heterotaxia (a heart disorder characterised by arterial defects), have beenfound to have points mutations in the Cx43-encoding gene, as a result of
which a potential phosphorylation site within the C terminus is disrupted. Consequently, although these mutant Cx43 molecules still form functional gap
junction channels, their response to protein kinase activation is impaired.This domain is found in the C-terminal region of these proteins.
This entry includes coiled-coil and C2 domain-containing protein 1A/B (CC2D1A/B, also known as Freud-1/2). CC2D1A is involved in many pathways, including nuclear factor kappaB, PDK1/Akt, cAMP/PKA, Notch and bone morphogenetic protein []. It is a calcium-regulated repressor of serotonine receptor 5-HT1A and dopamine-D2 receptor expression [,
]. CC2D1B binds to the 5-HT1A DRE and represses the human 5-HT1A receptor gene to regulate its expression in non-serotonergic cells and neurons [].CC2D1A and CC2D1B have also been shown to interact with the CHMP4 family of proteins, the major subunit of the ESCRT-III complex. They may regulate degradation and signaling of EGFR and TLR4 [
].CC2D1A and CC2D1B share conserved domains, including several DM14 domains that are specific to this protein family, a C-terminal helix-loop-helix domain, and a C2 domain. The CC2D1A C2 domain is thought to be calcium insensitive and it lacks several acidic residues that mediate calcium binding of the PKC C2 domain. In addition, it contains a poly-basic insert that is not present in calcium-dependent C2 domains and may function as a nuclear localization signal [
]. The CC2D1B C2 domain appears to be essential for its DNA binding and repressor function; it may mediate protein-protein interactions []. Mutations in the CC2D1A gene has been linked to nonsyndromic mental retardation [
,
].
Large-conductance mechanosensitive channel/anditomin synthesis protein L
Type:
Family
Description:
Mechanosensitive ion channels (MscL) play a critical role in transducing physical stresses at the cell membrane into an electrochemical response. MscL is a protein which forms a channel organised as a homopentamer, with each subunit containing two transmembrane regions [
,
,
]. Prokaryotes harbor a large-conductance mechanosensitive channel (gene mscL) that opens in response to stretch forces in the membrane lipid bilayer and participate in the regulation of osmotic pressure changes within the cell []. MscL has a conserved domain architecture which comprises an amphipathic α-helix (S1) that lies along the cytoplasmic membrane, a highly conserved first transmembrane domain (TM1) that forms the pore constriction, a periplasmic loop, a second transmembrane domain (TM2) that faces the lipid membrane, and a linker that leads to a cytoplasmic α-helical bundle [].This family also includes anditomin synthesis protein L (AndL), which is part of the gene cluster that mediates the biosynthesis of anditomin. Its role of in this pathway is not known [
].
The function of this domain is unknown, but it is found at the C terminus of bacteriophage N4 adsorption protein A (NfrA) in association with an N-terminal region of Tetratricopeptide (TPR) repeats. NfrA serves as the phage receptor [
].
Histone-like protein H-NS, C-terminal domain superfamily
Type:
Homologous_superfamily
Description:
This entry represents the C-terminal domain superfamily of the H-NS DNA binding protein. It is composed of an antiparallel β-sheet, an α-helix and a 3 (10)-helix which form a hydrophobic core, stabilising the whole structure. This domain has been found to bind to DNA [
].
RAG-2 is an essential component of the lymphoid-specific recombination activating gene RAG1/2 V(D)J recombinase mediating antigen-receptor gene assembly. It contains an acidic hinge region implicated in histone-binding, a non-canonical plant homeodomain (PHD) finger followed by a C-terminal extension of 40 amino acids that is essential for phosphoinositide (PtdIns)-binding. [
,
,
].This domain, a non-canonical plant homeodomain (PHD) finger, is found at the C terminus of the Recombination activating gene 2 (RAG2) protein. The PHD finger is a chromatin-binding module that has been shown bound to histone H3 trimethylated at lysine 4 (H3K4me3) and influences V(D)J recombination [
].
Cysteine and histidine-rich domain-containing protein 1
Type:
Family
Description:
This entry includes Cysteine and histidine-rich domain-containing protein 1 (CHRD1) which contains a CHORD (cysteine- and histidine-rich) domain. CHORDs are 60-amino acid modules that bind two zinc ions. They are usually arranged in tandem and are found in all tested eukaryotes, with the exception of yeast, where they are involved in processes ranging from pressure sensing in the heart to maintenance of diploidy in fungi, and exhibit distinct protein-protein interaction specificity. Six cysteine and two histidine residues are invariant within the CHORD domain. Three other residues are also invariant and some positions are confined to positive, negative, or aromatic amino acids [
,
]. Silencing of the Caenorhabditis elegans CHORD-containing gene results in semisterility and embryo lethality, suggesting an essential function of the wild-type gene in nematode development. The CHORD domain is sometimes found N-terminal to the CS domain,
, in metazoan proteins, but occurs separately from the CS domain in plants. This association is thought to be indicative of an functional interaction between CS and CHORD domains [
].
Conserved hypothetical protein CHP02574, addiction module
Type:
Family
Description:
This entry defines several short bacterial proteins, typically about 75 amino acids long, which are always found as part of a pair (at least) of small genes. The other protein in the pair always belongs to a family of plasmid stabilisation proteins (
). It is likely that this protein and its partner comprise some form of addiction module - a pair of genes consisting of a stable toxin and an unstable antitoxin which mediate programmed cell death [
] - although these gene pairs are usually found on the bacterial main chromosome.
Rho GTPase-activating proteins (RhoGAPs or ARHGAPs) bind to Rho proteins and enhance the hydrolysis rates of bound GTP. ARHGAP9 functions as a GAP for Rac and Cdc42, but not for RhoA [
]. It negatively regulates cell migration and adhesion []. It also acts as a docking protein for the MAP kinases Erk2 and p38alpha, and may facilitate cross-talk between the Rho GTPase and MAPK pathways to control actin remodeling []. It contains SH3, WW, Pleckstin homology (PH), and RhoGAP domains. This entry represents the SH3 domain found in ARHGAP9.
The genome polyprotein contains: caspid protein C, envelope glycoproteins E1 and E2, protein P7, nonstructural protein NS2, protease/helicase NS3, nonstructural proteins NS4A and NS4B (this family), NS5A and NS5B.
The small proteins NS2A, NS2B, NS4A and NS4B are hydrophobic, suggesting a possible membrane-related function [
].It is known that NS4B interacts with NS4A and NS3 to form a large
replicase complex to direct the viral RNA replication []. NS3 and NS5 may also play a role in the viral RNA replication.
Conserved hypothetical protein CHP02664, nitrate reductase-associated
Type:
Family
Description:
Proteins in this entry are found in the Cyanobacteria, and are mostly encoded near nitrate reductase and molybdopterin biosynthesis genes. Molybdopterin guanine dinucleotide is a cofactor for nitrate reductase. These proteins are sometimes annotated as nitrate reductase-associated proteins, though their function is unknown.
Molybdenum cofactor biosynthesis protein A, archaea
Type:
Family
Description:
This entry consists of archaeal proteins which are predicted to be functionally equivalent to MoaA (molybdenum cofactor biosynthesis protein A, cyclic pyranopterin monophosphate synthase or GTP 3',8-cyclase) from bacteria (see ).
Thioredoxin-related transmembrane protein 2, thioredoxin domain
Type:
Domain
Description:
This entry represents the thioredoxin (TRX) domain found in thioredoxin-related transmembrane protein 2 (TMX2). In TMX2, the TRX domain redox active CXXC motif is replaced with SXXC. In addition to the TRX domain, TMX2 may contain an N-terminal signal peptide, a potential transmembrane domain, an Myb DNA-binding domain repeat signature, an endoplasmic reticulum (ER) membrane retention signal (KKXX-like motif), and a dileucine motif in the tail [
,
].
Polycystic kidney diseases (PKD) are disorders characterised by large numbers of cysts distributed throughout grossly-enlarged kidneys. Cyst
development is associated with impairment of kidney function, and ultimately kidney failure and death [,
]. Most cases of autosomal dominant PKD result from mutations in the PKD1 gene that cause premature protein termination. A second gene for autosomal dominant polycystic kidney disease has been identified by positional cloning []. The predicted 968-amino acid sequence of the PKD2 gene product (polycystin-2) contains 6 transmembrane domains, with intracellular N- and C-termini. Polycystin-2 shares some similarity with the family of voltage-activated calcium (and sodium) channels, and contains a potential calcium-binding domain [].Polycystin-2 is strongly expressed in ovary, foetal and adult kidney, testis, and small intestine. Polycystin-1 requires the presence of this protein for stable expression and is believed to interact with it via its C terminus. All mutations between exons 1 and 11 result in a truncated polycystin-2 that lacks a calcium-binding EF-hand domain and the cytoplasmic domains required for the interaction of polycystin-2 with polycystin-1 [
]. PKD2, although clinically milder than PKD1, has a deleterious impact on life expectancy.
CD2 antigen cytoplasmic tail-binding protein 2/Lin1
Type:
Family
Description:
CD2BP2, also known as U5-52K or LIN1, is a component of the U5 snRNP complex and acts as a splicing factor [
,
]. It also may play a role in the immune response as CD2 receptor binding protein 2 (CD2BP2) []. Lin1 from Saccharomyces cerevisiae is a non-essential component of U5 snRNP []; it may link together proteins involved in chromosome segregation, mRNA splicing and DNA replication [].
This is a small α-helical domain with two acidic residues conserved in a predicted loop between two of its helices [
]. The domain is mainly found in polyvalent proteins of conjugative elements [].
V-set and immunoglobulin domain-containing protein 4
Type:
Family
Description:
V-set and Ig domain-containing 4 (VSIG4) is a strong negative regulator of T cell proliferation and IL-2 production [
]. It also negatively regulates macrophage activation by activating the PI3K/Akt-STAT3 pathway, leading to pyruvate dehydrogenase kinase-2 (PDK2) upregulation and subsequent phosphorylation of pyruvate dehydrogenase, which results in reduction in pyruvate/acetyl-CoA conversion, reduction in mitochondrial reactive oxygen species secretion, and macrophage inhibition [].
This entry represents the BamA (also known as YaeT) family of proteins. BamA forms part of the outer membrane protein assembly complex, which is involved in assembly and insertion of β-barrel proteins into the outer membrane in Gram-negative bacteria [
]. Contact-dependent growth inhibition (CDI) systems are widespread among Gram-negative bacteria, enabling them to bind to neighbouring bacterial cells and deliver protein toxins that inhibit cell growth. Escherichia coli EC93 CdiAEC93 recognised BamA protein as a receptor. The variations in the CdiAEC93-binding epitope (loops 6 and 7) of BamA restricts CDIEC93 target cell selection, and hence play a role in self-nonself discrimination [
].
Isocitrate dehydrogenase/Hypothetical protein TT1725, C-terminal domain
Type:
Domain
Description:
This entry represents the C-terminal domain of Isocitrate dehydrogenase [NADP] from Rickettsia typhi and similar bacterial proteins. It is also found in the hypothetical protein TT1725 from Thermus thermophilus HB8. The sequence is conserved in three predicted prokaryotic proteins with unknown functions, including Deinococcus radiodurans, Stigmatella aurantiaca, and Mycobacterium leprae. The presence of positively-charged residues in the α1 helix suggests this region binds to a protein with a negatively charged region or to nucleic acids [].
Microsomal triglyceride transfer protein large subunit
Type:
Family
Description:
Microsomal triglyceride transfer protein large subunit (MTTP) catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces, and is required for the secretion of plasma lipoproteins that contain apolipoprotein B. It is a heterodimer consisting of a large MTP alpha-subunit and a protein disulfide isomerase (PDI) beta-subunit. Mutations in microsomal triglyceride transfer protein (MTP) cause abetalipoproteinemia [
,
,
].
General secretion pathway protein D (GspD) is the secretin component of the type II secretion system. GspD is closely homologous to the type IV pilus outer membrane secretin PilQ (
) and to the type III secretion system pore YscC/HrcC (
). The N-terminal part of GspD extends into the periplasm and may interact with secreted proteins as well as T2SS partner proteins [
]. The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space [
]. T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK []. GspD has been shown to interact with the inner membrane component GspC []. The T2SS pseudopilus is a periplasmic filament composed of the major pseudopilin, EpsG, and four minor pseudopilins, EpsH, EpsI, EpsJ and EpsK. Pseudopilus is assembled by the polymerization of GspG (also known as PulG) subunits. Pseudopilin proteins have a conserved N-terminal hydrophobic segment followed by a more variable C-terminal periplasmic and globular domain [
].
This family includes Cilia- and flagella- associated protein 210 (CFAP210, also known as Coiled-coil domain-containing protein 173) which appears to be a microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating [
].
Rotaviruses consist of three concentric protein shells. The intermediate
(middle) protein layer contains VP6, the major internal structural protein. VP6 is the most abundant protein in the virion and is involved in virion assembly,
VP6 possesses the ability to interact with VP2, VP4 and VP7 [,
].
Rho-associated protein kinases (ROCKs) were originally identified as small GTPase Rho effectors. Later, ROCKs were found actively phosphorylating many actin-binding proteins and intermediate filament proteins to modulate their functions [
]. Two ROCK isoforms have been identified:ROCK1 (ROKb, p160ROCK) and ROCK2. As major downstream effectors of the small GTPase RhoA, they regulate cellular contraction, motility, morphology, polarity, cell division, and gene expression [
,
,
].This entry represents the HR1 domain found in Rho-associated protein kinase 2 (ROCK2), which is essential for the formation of stress fibres [
]. ROCK2 contains an N-terminal extension, a catalytic kinase domain, and a long C-terminal extension, which contains a Rho-binding HR1 domain and a pleckstrin homology (PH) domain. ROCK2 is auto-inhibited by HR1 and PH domains interacting with the catalytic domain. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family [].
GspE is a cytoplasmic hexameric ATPase of the type II secretion system. It contains three domains (N1E, N2E and CTE) of which the N1E domain is associated with the cytoplasmic domain of the inner membrane protein GspL [
]. The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space [
]. T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK []. GspD has been shown to interact with the inner membrane component GspC []. The T2SS pseudopilus is a periplasmic filament composed of the major pseudopilin, EpsG, and four minor pseudopilins, EpsH, EpsI, EpsJ and EpsK. Pseudopilus is assembled by the polymerization of GspG (also known as PulG) subunits. Pseudopilin proteins have a conserved N-terminal hydrophobic segment followed by a more variable C-terminal periplasmic and globular domain [
].
This entry represents the BRCT domain of TP53BP1 and its orthologues. It corresponds to the first BRCT domain of TP53BP1 and hsr-9.This entry includes TP53-binding protein 1 (TP53BP1, also known as p53BP1 or 53BP1) and its orthologues, such as DNA repair protein RAD9 from S.cerevisiae and Crb2 from S.pombe [
,
,
,
,
,
,
,
,
]. TP53BP1 is a double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis [,
]. TP53BP1 and its homologue from C.elegans hsr-9 contain two tandem BRCT domains, while the fungal orthologues contain one BRCT domain [,
]. Crb2, is a checkpoint mediator required for the cellular response to DNA damage [].
This entry represents the second BRCT domain of TP53-binding protein 1 (TP53BP1, also known as p53BP1 or 53BP1) and its homologue from C.elegans [
,
]. TP53BP1 is a double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis [
,
,
,
,
,
,
,
,
,
].
Microcystin LR degradation protein MlrC, N-terminal
Type:
Domain
Description:
Proteins in this entry are involved in degradation of the cyanobacterial heptapeptide hepatotoxin microcystin LR, and are encoded in the mlr gene cluster [
]. MlrC from Sphingomonas wittichii (strain RW1 / DSM 6014 / JCM 10273) is believed to mediate the last step of peptidolytic degradation of the tetrapeptide. It is suspected to be a metallopeptidase based on homology to known peptidases and its inhibition by metal chelators. The proteins encoded by the mlr cluster may be involved in cell wall peptidoglycan cycling and subsequently act fortuitously in hydrolysis of microcystin LR.This entry represents the N-terminal region of these proteins.
Bluetongue virus VP6 protein binds ATP and exhibits an
RNA-dependent ATPase function and a helicase activity thatcatalyses the unwinding of double-stranded RNA substrates [
]. VP6 from five United Statesprototype bluetongue virus (BTV) serotypes contain unusually high concentrations of glycine,
few aromatic amino acids, but a high concentration of charged amino acids,a characteristic of hydrophilic proteins [
].VP6 is an inner capsid protein that surrounds the genomic DS-RNA. Its
hydrophilic nature coupled with a capability to bind ss- and ds-RNA,suggests that it interacts directly with the BTV genomic RNA.
This domain is found in the major vault protein.The major vault protein is the major polypeptide component of a large cellular ribonuclear protein complex found in the cytoplasm of eukaryotic cells (known as vaults). Several roles for vaults have been proposed. Vault proteins have been associated with development of multi-drug resistance [
]. They have also being implicated in the regulation of several cellular processes including transport mechanisms, signal transmission and immune responses [,
].
Shortage in chiasmata 1 orthologue, the plant SHOC1 orthologue in animals, has been shown to act at mid-stage steps of the crossover (CO) formation process. It also interacts with TEX11, another protein important for the formation of COs. SHOC1 has associated ATPase activity, but lacks endonuclease activity, so it has been speculated that SHOC1 may protect against dissociation by anti-crossover activities instead of having a role in cleaving recombination intermediates to produce COs [
].
This protein is encoded by genes which are found in type III secretion operons, and has been shown to be essential for the invasion phenotype in Salmonella and a component of the secretion apparatus [
]. The protein is known as OrgA in Salmonella due to its oxygen-dependent expression pattern in which low-oxygen levels up-regulate the gene []. In Shigella it is called MxiK and has been shown to be essential for the proper assembly of the needle complex, which is the core component of type III secretion systems []. The putative uncharacterized protein YgeO from E. coli is also included in this entry. YgeO' is reported in ecogene as being homologous to OrgA and MxiK.
Four genes from the major Bacillus subtilis chemotaxis locus have been shown to encode proteins that are similar to the Salmonella typhimurium FlgB, FlgC, FlgG and FliF proteins; a further gene product is similar to the Escherichia coli FliE protein [
]. All of these proteins are thought to form part of the hook-basal body complex of the bacterial flagella []. The FlgB, FlgC and FlgG proteins are components of the proximal and distal rods; FliF forms the M-ring that anchors the rod assembly to the membrane; but the role of FliE has not yet been determined []. The similarity between the proteins in these two organisms suggests that the structures of the M-ring and the rod may be similar []. Nevertheless, some differences in size and amino acid composition between some of the homologues suggest the basal body proteins may be organised slightly differently within B. subtilis [].From gel electrophoresis and autoradiography of 35S-labelled S. typhimurium hook-basal body complexes and the deduced number of sulphur-containing residues in FliE, the stoichiometry of the protein in the hook-basal body complex has been estimated to be about nine subunits [
]. FliE does not undergo cleavage of a signal peptide, nor does it show any similarity to the axial components like the rod or hook proteins, which are thought to be exported by the flagellum-specific export pathway []. On this evidence, it has been suggested that FliE may be in the vicinity of the MS ring, perhaps acting as an adaptor protein between ring and rod substructures [].
Armadillo-like helical domain-containing protein 3, C-terminal
Type:
Domain
Description:
This is the C-terminal domain of Armadillo-like helical domain-containing protein 3 (ARMH3), the previously uncharacterised peripheral Golgi protein C10orf76. ARMH3 interacts with and is involved in GBF1 recruitment, Golgi maintenance and protein secretion [
,
]. C10orf76 associates with the lipid kinase PI4KB that increases phosphatidylinositol 4-phosphate (PI4P) levels at the Golgi, being essential for the viral replication of specific enteroviruses []. The function of this domain is unknown.
