GspC is part of the type 2 secretion systems (T2SSs). GspC interacts with GspD. It is an inner membrane protein consisting of a short N-terminal cytoplasmic sequence and analpha-helical transmembrane segment, followed by two periplasmic domains: a so-called homology region (HR) and a C-terminal PDZ domain [
].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 domain is found in a wide range of outer membrane proteins. This domain assumes a membrane bound β-barrel fold. It is part of a Pfam clan that includes other outer membrane protein β-barrel domains.
Flagellar motor switch protein FliG, alpha-helical
Type:
Homologous_superfamily
Description:
This superfamily represents an α-α superhelical domain found in the flagellar motor switch protein FliG. The flagellar motor switch regulates the direction of flagellar rotation and swimming behaviour in certain bacteria [
]. The switch is a complex apparatus that responds to signals transduced by the chemotaxis sensory signalling system during chemotactic behaviour. CheY, the chemotaxis response regulator, is believed to act directly on the switch to induce tumbles in the swimming pattern [].The switch complex comprises at least three proteins - FliG, FliM and FliN. It has been shown that FliG interacts with FliM, FliM interacts with itself, and FliM interacts with FliN. Several residues within the middle third of FliG appear to be strongly involved in the FliG-FliM interaction, with residues near the N- or C-termini being less important. Such clustering suggests that FliG-FliM interaction plays a central role in switching.
T-complex protein 10, C-terminal domain superfamily
Type:
Homologous_superfamily
Description:
This entry represents a C-terminal domain found in members of the T complex protein 10 family. This domain contains unusual G repeats [
]. Centromere protein J (also known as Centrosomal-P4.1-associated-protein, CPAP), a member of the TCP10 family, plays an important role in cell division and centrosome function by participating in centriole duplication [,
]. It inhibits microtubule nucleation from the centrosome and depolymerises taxol-stabilised microtubules []. It may also be involved in the control of centriolar-microtubule growth by acting as a regulator of tubulin release []. T-complex is involved in spermatogenesis in mice [].This domain, also known as TCP and G-box, is essential for the tethering of pericentriolar material (PCM), the principle site for microtubule nucleation and anchoring. It adopts an extended single-layer antiparallel β-sheet configuration [
]. Mutations in this region are associated with primary microcephaly [,
].
tRNA 5-methylaminomethyl-2-thiouridine biosynthesis bifunctional protein MnmC
Type:
Family
Description:
This entry represents the tRNA 5-methylaminomethyl-2-thiouridine biosynthesis bifunctional protein MnmC. It has FAD-dependent oxidoreductase and methytransferase activity ([intenz:1.5.-.-] and [intenz:2.1.1.-]respectively).
PknD is a mycobacterial transmembrane protein with a cytosolic kinase domain and an extracellular sensor domain that contains NHL repeats [
]. It plays a key role in the development of central nervous system tuberculosis, by mediating the invasion of host brain endothelia []. The NHL (NCL-1, HT2A and LIN-41) repeat is found in multiple tandem copies, typically as 6 instances. It is about 40 residues long and resembles the WD repeat and other β-propeller structures [].
Double-stranded DNA deaminase immunity protein DddI
Type:
Family
Description:
DddI is an immunity protein component of a toxin-immunity protein module, which functions as a cellular contact-dependent growth inhibition (CDI) system [
].
This domain is found repeated three times in the N-terminal half of the gliding motility-related SprA proteins. The role of this domain in motility is uncertain [
]. It is also found in proteins required for secretion [].
60S ribosomal subunit assembly/export protein Loc1
Type:
Family
Description:
Loc1 is required for efficient assembly and nuclear export of the 60S ribosomal subunit [
,
]. Budding yeast Loc1 recognizes double-stranded RNA structures and is required for efficient localization of ASH1 mRNA [].
The flagellar motor switch in Escherichia coli and Salmonella typhimurium regulates the
direction of flagellar rotation and hence controls swimming behaviour [].The switch is a complex apparatus that responds to signals transduced by the
chemotaxis sensory signalling system during chemotactic behaviour []. CheY,the chemotaxis response regulator, is believed to act directly on the switch
to induce tumbles in the swimming pattern, but no physical interactions of CheY and switch proteins have yet been demonstrated.
The switch complex comprises at least three proteins - FliG, FliM and FliN.
It has been shown that FliG interacts with FliM, FliM interacts with itself,and FliM interacts with FliN [
]. Several residues within the middle thirdof FliG appear to be strongly involved in the FliG-FliM interaction, with
residues near the N- or C-termini being less important []. Such clusteringsuggests that FliG-FliM interaction plays a central role in switching.
Analysis of the FliG, FliM and FliN sequences shows that none are especially
hydrophobic or appear to be integral membrane proteins []. This result isconsistent with other evidence suggesting that the proteins may be
peripheral to the membrane, possibly mounted on the basal body M ring [,
]. FliG is present in about 25 copies per flagellum.This entry represents the C-terminal domain of FliG, the structure of which is known. This domain functions specifically in motor rotation [
].
This family represents a diverse group of multifunctional proteins that regulate cellular signalling events downstream of G-protein coupled receptors (GPCRs). They belong to the R7 (Neuronal RGS) subfamily, which includes RGS6, RGS7, RGS9, and RGS11, all of which, in humans, are expressed predominantly in the nervous system [
,
]. They form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes []. In addition, R7 proteins were found to bind many other proteins outside of the G protein signalling pathways including: m-opioid receptor, beta-arrestin, alpha-actinin-2, NMDAR, polycystin, spinophilin, guanylyl cyclase, among others. They have an RGS domain, which is an essential part of the R7 protein subfamily. These proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis [].This entry also includes Egl-10, an orthologue of human RGS7 from C. elegans.
Mercuric resistence transcriptional repressor protein MerD
Type:
Family
Description:
This entry represents a transcriptional repressor protein of the MerR family whose expression is regulated by the mercury-sensitive transcriptional activator, MerR. MerD has been shown to repress the transcription of the mer operon [
].
This entry represents the BACK (BTB and C-terminal Kelch) domain of KEAP1 and similar animal proteins.Kelch-like ECH-associated protein 1 (KEAP1, also known as KLHL19) is a BTB-Kelch substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex that functions as a sensor for thiol-reactive chemopreventive compounds and oxidative stress. It targets NFE2L2/NRF2 (a transcription factor) for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression [
,
]. Another KEAP1 substrate, PGAM5, a Bcl-XL-interacting protein, has also been identified [].The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].
This entry represents the BACK (BTB and C-terminal Kelch) domain of ENC1.Ectoderm-neural cortex protein 1 (ENC1), also known as kelch-like protein 37 (KLHL37), is expressed in the central nervous system (CNS), where it interacts with actin and contributes to the organisation of the cytoskeleton during the specification of neural fate [
]. ENC1 functions as a negative regulator of transcription factor Nrf2 (a regulator of a cellular defense mechanism against environmental insults) through suppressing Nrf2 protein translation []. It plays a pivotal role in neuronal and adipocyte differentiation [].The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].
Twist-related protein 2, basic helix-loop-helix domain
Type:
Domain
Description:
This entry represents the basic helix-loop-helix (bHLH) domain found in Twist2 and related proteins from vertebrates.Twist-related protein 2 (Twist2) is a bHLH transcriptional factor that regulates the development of mesenchymal tissues and plays a critical role in embryogenesis. It binds to the E-box consensus sequence 5'-CANNTG-3' as a heterodimer and inhibits transcriptional activation by MYOD1, MYOG, MEF2A and MEF2C [
,
]. Twist2 is also involved in cancer progression and is a valuable biomarker for certain cancer types [,
,
]. Mutations in this protein are associated with other human disorders such as ectodermal dysplasias [,
].
Twist-related protein 1, basic helix-loop-helix domain
Type:
Domain
Description:
This entry represents the basic helix-loop-helix (bHLH) domain found in Twist1 and related proteins mainly from vertebrates.Twist-related protein 1 (Twist1) is a bHLH transcriptional regulator that inhibits myogenesis by sequestrating E proteins, inhibiting trans-activation by MEF2, and inhibiting DNA-binding by MYOD1 through physical interaction. It also represses expression of proinflammatory cytokines such as TNFA and IL1B [
,
] and plays an essential role in tooth morphogenesis []. In addition, Twist1 is involved in cancer development and progression [,
,
]. Mutations in this protein are associated with other genetic human diseases with symptoms related to malformations [,
].
This entry represents the hypothetical protein YqbG from Bacillus species, as well as related proteins from other bacteria. YqbG exists as a monomer, consisting of four α-helices with a right-handed twist, arranged in a left-handed superhelix [
].
Methanogenesis regulatory protein FilR1, middle domain
Type:
Domain
Description:
This archaeal domain of unknown function has been found at the middle of Methanogenesis regulatory protein FilR1 [
,
] and at the C-terminal of several transcriptional regulators of the ArsR family (see ). FilR1 is a member of the two-component regulatory system FilI/FilRs which is involved in the regulation of methanogenesis.
Glucan-binding protein C/Surface antigen I/II, V-domain
Type:
Domain
Description:
This domain is found in glucan-binding protein C (GbpC) and in the V-region of surface protein antigen; both these proteins belong to the Spa family of Streptococcal proteins [
]. This domain consists of a β-supersandwich of 18 β-strands in two sheets. There are at least four types of glucan-binding proteins (Gbp) in Streptococcus mutans, GbpA, GbpB, GbpC and GbpD. These proteins promote the adhesion of Streptococcal bacteria to teeth and are associated with dental caries [
]. GbpC is a cell-wall anchoring protein that plays an important role in sucrose-dependent adhesion by binding to soluble glucan synthesised by glucosyltransferase D (GTFD) [].Spa antigens I/II are multi-functional proteins expressed at the cell wall surface of oral Streptococci, where they function as adhesins. Antigens I/II recognise a wide range of ligands. They exert an immunomodulatory effect on human cells and are important in inflammatory disorders, such as dental caries. These proteins can be divided into seven regions: signal peptide, N-terminal, A-region (alanine-rich), V-region (variable domain), P-region (proline-rich), C-terminal domain, and a cell wall anchor motif. The V-region is the central domain and exhibits the greatest variability in sequence, and is responsible for binding monocyte receptors, its binding stimulating the release of TNF-alpha from the monocytes. The crystal structure of the V-region revealed a lectin-like fold that displays a putative preformed carbohydrate-binding site stabilised by a metal ion [
].
Immunodeficiency virus transactivating regulatory protein (Tat)
Type:
Family
Description:
Like other lentiviruses, Human immunodeficiency virus 1 (HIV-1) encodes a trans-activating regulatory protein (Tat), which is essential for efficient transcription of the viral genome [
,
]. Tat acts by binding to an RNA stem-loop structure, the trans-activating response element (TAR), found at the 5' ends of nascent HIV-1 transcripts. In binding to TAR, Tat alters the properties of the transcription complex, recruits a positive transcription elongation complex (P-TEFb) and hence increases the production of full-length viral RNA []. Tat protein also associates with RNA polymerase II complexes during early transcription elongation afterthe promoter clearance and before the synthesis of full-length TAR RNA transcript. This interaction of Tat with RNA polymerase II elongation
complexes is P-TEFb-independent. There are two Tat binding sites on each transcription elongation complex; one is located onTAR RNA and the other one on RNA polymerase II near the exit site for nascent mRNA transcripts which suggests that two Tat molecules are
involved in performing various functions during a single round of HIV-1 mRNA synthesis []. The minimum Tat sequence that can mediate specific TAR binding
in vitrohas been mapped to a basic domain of 10 amino acids, comprising mostly Arg and Lys residues. Regulatory activity, however, also requires the 47 N-terminal residues, which interact with components of the transcription complex and function as a transcriptional activation domain [
,
,
].
This cysteine rich repeat contains four cysteines. It is found in multiple copies in metazoan proteins, single copies occur in some bacterial species and is absent from the fungi.The Golgi apparatus protein 1 (GLG1), which is located in Golgi cisterns of various cell types, can bind fibroblast growth factor and E-selectin. Sixteen cysteine-rich GLG1 repeats form the core of the protein and are located in the lumen. The C-terminal part of GLG1 is composed of a transmembrane region and a short cytoplasmic tail. The Cys-rich GLG1 repeat is a ~60 amino acid module that contains 4 Cys residues, which can form intrachain disulphide bridges [
]. Homologues of the vertebrate GLG1/Golgi sialoglycoprotein MG-160 (Mg160)/E-selectin ligand 1 (ESL1)/cysteine-rich fibroblast growth factor receptor 1 (CFR1)/latent transforming growth factor-beta complex protein 1 (LTCP-1) have been found in insects and the nematode Caenorhabditis elegans [].
Nitrogen regulatory protein areA, GATA-like domain
Type:
Domain
Description:
This entry represents fungal proteins containing GATA domains, including nitrogen regulatory protein areA, a transcription activator that binds the consensus DNA element 5'-CGATAG-3' and mediates nitrogen metabolite repression [
]. The entry also contains that is thought to be a negative regulator of RAS-cAMP pathway in S. cerevisiae and the S. pombe member is a GAF1 transcription factor
.
Developmental pluripotency-associated protein 2/4, C-terminal domain
Type:
Domain
Description:
This domain has been characterised in the finding of a developmental pluripotency associated gene (Dppa) in the lower vertebrate Xenopus laevis [
]. Previous to this discovery, Dppa genes were known only in higher vertebrates.
Developmental pluripotency-associated protein 2/4, central domain
Type:
Domain
Description:
Developmental pluripotency associated genes (Dppa) in lower vertebrates have remained undetected until the discovery of a Dppa homologue in Xenopus laevis []. This entry represents a central domain of Dppa 2/4.
CpG-methylation is a frequently occurring epigenetic modification of vertebrate genomes resulting in transcriptional repression. This domain is found at the C terminus of the methyl-CpG-binding domain (MBD) containing proteins MBD2 [
] and MBD3 []. The latter was shown to not bind directly to methyl-CpG DNA but rather interact with components of the NuRD/Mi2 complex [], an abundant deacetylase complex.
The adaptor protein complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules [
]. Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3). Subunits of clathrin-associated adaptor protein complex 1 play a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or in endosomes.This group represents an adaptor protein complex AP-1, gamma subunit.
Nuclear factor related to kappa-B-binding protein, also known as INO80 complex subunit G, is a component of the metazoan INO80 complex involved in chromatin remodelling, transcription regulation, DNA replication and DNA repair [
,
].
This entry represents the C terminus of protein ENHANCED DISEASE RESISTANCE 2 (EDR2) from plants. EDR2 is a negative regulator of the salicylic acid- (SA-) mediated resistance to pathogens, including the biotrophic powdery mildew pathogens Golovinomyces cichoracearum and Blumeria graminis, and the downy mildew pathogen Hyaloperonospora parasitica, probably by limiting the initiation of cell death and the establishment of the hypersensitive response (HR) [
,
].
Mismatch repair contributes to the overall fidelity of DNA replication and is essential for combating the adverse effects of damage to the genome. It involves the correction of mismatched base pairs that have been missed by the proofreading element of the DNA polymerase complex. The post-replicative Mismatch Repair System (MMRS) of Escherichia coli involves MutS (Mutator S), MutL and MutH proteins, and acts to correct point mutations or small insertion/deletion loops produced during DNA replication [
]. MutS and MutL are involved in preventing recombination between partially homologous DNA sequences. The assembly of MMRS is initiated by MutS, which recognises and binds to mispaired nucleotides and allows further action of MutL and MutH to eliminate a portion of newly synthesized DNA strand containing the mispaired base []. MutS can also collaborate with methyltransferases in the repair of O(6)-methylguanine damage, which would otherwise pair with thymine during replication to create an O(6)mG:T mismatch []. MutS exists as a dimer, where the two monomers have different conformations and form a heterodimer at the structural level []. Only one monomer recognises the mismatch specifically and has ADP bound. Non-specific major groove DNA-binding domains from both monomers embrace the DNA in a clamp-like structure. Mismatch binding induces ATP uptake and a conformational change in the MutS protein, resulting in a clamp that translocates on DNA. MutS is a modular protein with a complex structure [
], and is composed of:N-terminal mismatch-recognition domain, which is similar in structure to tRNA endonuclease.Connector domain, which is similar in structure to Holliday junction resolvase ruvC.Core domain, which is composed of two separate subdomains that join together to form a helical bundle; from within the core domain, two helices act as levers that extend towards (but do not touch) the DNA.Clamp domain, which is inserted between the two subdomains of the core domain at the top of the lever helices; the clamp domain has a β-sheet structure.ATPase domain (connected to the core domain), which has a classical Walker A motif.HTH (helix-turn-helix) domain, which is involved in dimer contacts.The MutS family of proteins is named after the Salmonella typhimurium MutS protein involved in mismatch repair. Homologues of MutS have been found in many species including eukaryotes (MSH 1, 2, 3, 4, 5, and 6 proteins), archaea and bacteria, and together these proteins have been grouped into the MutS family. Although many of these proteins have similar activities to the E. coli MutS, there is significant diversity of function among the MutS family members. Human MSH has been implicated in non-polyposis colorectal carcinoma (HNPCC) and is a mismatch binding protein [
].This diversity is even seen within species, where many species encode multiple MutS homologues with distinct functions []. Inter-species homologues may have arisen through frequent ancient horizontal gene transfer of MutS (and MutL) from bacteria to archaea and eukaryotes via endosymbiotic ancestors of mitochondria and chloroplasts []. This entry represents the N-terminal domain of proteins in the MutS family of DNA mismatch repair proteins. The N-terminal domain of MutS is responsible for mismatch recognition and forms a 6-stranded mixed β-sheet surrounded by three α-helices, which is similar to the structure of tRNA endonuclease.
Nitrogen regulatory protein PII/ATP phosphoribosyltransferase, C-terminal
Type:
Homologous_superfamily
Description:
This entry represents a structural domain found in the nitrogen regulatory protein PII, in ATP phosphribosyltransferases (C-terminal domain), and in some bacterial hypothetical proteins. This domain consists of a ferredoxin-like alpha/beta sandwich, which forms trimeric structures with orthogonally packed β-sheets around a three-fold axis. PII is a tetrameric protein encoded by glnB that functions as a component of the adenylation cascade involved in the regulation of glutamine synthetase activity [
]. PII helps regulate the level of glutamine synthetase in response to nitrogen source availability. In nitrogen-limiting conditions, PII is uridylylated to form PII-UMP, which allows the deadenylation of glutamine synthetase, thus activating the enzyme. Conversely, in nitrogen excess, PI-UMP is deuridylated to PII, promoting the adenylation and deactivation of glutamine synthetase [].ATP phosphoribosyltransferase is the first enzyme of the histidine pathway. It is allosterically regulated, controlling the flow of intermediates through the pathway. The C-terminal domain is the regulatory region of the protein, which binds the allosteric inhibitor histidine [
].
Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase implicated
in many cellular processes, including the regulation of metabolic enzymes and proteins involved in signal transduction [
,
]. PP2A is a trimercomposed of a 36kDa catalytic subunit, a 65kDa regulatory subunit
(subunit A) and a variable third subunit (subunit B) [,
]. Subunits B can be classified into three subfamilies, the R2/B/PR55/B55, the R3/B''/PR72/PR130/PR59 and the R5/B'/B56 families. This entry represent the R2/B/PR55/B55 family, which exists in
Drosophila melanogaster and yeast, and has up to three isoforms in mammals (alpha/beta/gamma) [,
]. PR55 may act as a substrate recognition unit, or may help to target the enzyme to thecorrect subcellular location [
]. In budding yeasts, it is also known as Cdc55, which is essential for the spindle assembly checkpoint (SAC) []. In flies, it is also known as PP2A-twins, which collaborates with polo kinase for cell cycle progression and centrosome attachment to nuclei in Drosophila embryos [].
Carbon catabolite-derepressing protein kinase, ubiquitin-associated domain
Type:
Domain
Description:
This ubiquitin-associated (UBA) domain is found in yeast carbon catabolite-derepressing protein kinases (Snf1) and similar proteins from fungi. Mutations in this domain significantly alter SNF1 kinase activation and biological activity [
].Snf1, also called yeast adenosine monophosphate (AMP)-activated protein kinase (AMPK), is a global regulator of carbon metabolism in the yeast Saccharomyces cerevisiae [
,
]. Snf1 is involved in the cellular responses to nutrient stress, as well as other environmental stresses [,
,
].
Kinesin-like protein KIF11-like, kinesin motor domain
Type:
Domain
Description:
This entry represents the kinesin motor domain of KIF11 and similar eukaryotic spindle pole proteins.This entry includes a group of kinesin-like proteins, including human Eg5/KIF11, its orthologue from Drosophila Klp61F, BimC from Emericella nidulans and CIN8 from Saccharomyces cerevisiae. These are spindle pole proteins, which participate in spindle assembly and chromosome segregation during cell division, required for spindle body separation [,
].
Circadian locomoter output cycles protein kaput-like
Type:
Family
Description:
This entry represents a group of animal proteins related to core components of the circadian clock, including the human proteins circadian locomoter output cycles protein kaput (CLOCK), neuronal PAS domain-containing protein 2 (NPAS2) and the circadian clock protein PASD1.CLOCK and NPAS2 are core clock components. CLOCK is a transcriptional activator that also has an intrinsic acetyltransferase activity, which enables circadian chromatin remodelling by acetylating histones and nonhistone proteins, including its own partner BMAL1 [
,
,
]. NPAS2 mediates the diurnal variation in the expression of GABARA1 receptor in the brain and contributes to the regulation of anxiety-like behaviors and GABAergic neurotransmission in the ventral striatum [,
].PASD1 functions as a nuclear repressor of the CLOCK-BMAL1 heterodimer-mediated transcriptional activation of the core clock components, acting as a suppressor of the biological clock that drives the daily circadian rhythms of cells throughout the body [
].
This entry represents the second MBT repeat of SCMH1 and similar proteins specific to vertebrates. MTB repeats are protein modules that recognise methylated lysine residues on histones. This repeat contains a semi-aromatic cage to accommodate methylated lysine residues and show specificity towards the lower methylation states of lysines.Sex comb on midleg homologue 1 (SCMH1) is the mammal homologue of Drosophila Sex comb on midleg (Scm). It is a component of PRC1 (Polycomb repressive complex 1), which acts as an E3 ubiquitin ligase, both for histone H2A to silence transcription and for geminin to regulate its stability. SCMH1 provides the complex with an interaction domain for geminin. It contains two MBT (malignant brain tumor) repeats [
,
,
,
,
,
].
This entry represents the first MBT repeat of SCMH1 and similar proteins specific to vertebrates. MTB repeats are protein modules that recognise methylated lysine residues on histones. Unlike other MTB repeats, this repeat does not contain a semi-aromatic cage and may not bind methylated lysine residues.Sex comb on midleg homologue 1 (SCMH1) is the mammal homologue of Drosophila Sex comb on midleg (Scm). It is a component of PRC1 (Polycomb repressive complex 1), which acts as an E3 ubiquitin ligase, both for histone H2A to silence transcription and for geminin to regulate its stability. SCMH1 provides the complex with an interaction domain for geminin. It contains two MBT (malignant brain tumor) repeats [
,
,
,
,
,
].
This entry represents ZMY11 and similar proteins from animals. Zinc finger MYND domain-containing protein 11 (ZMYND11 or ZMY11, also known as protein BS69) is a ubiquitously expressed nuclear protein acting as a transcriptional co-repressor in association with various transcription factors [
]. This protein specifically recognises H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation []. It is critical for the repression of a transcriptional program that is essential for tumour cell growth. It was originally identified as an adenovirus 5 E1A-binding protein that inhibits E1A transactivation, as well as c-Myb transcription [,
, ]. It also mediates repression, at least in part, through interaction with the co-repressor N-CoR []. Moreover, it interacts with Toll-interleukin 1 receptor domain (TIR)-containing adaptor molecule-1 (TICAM-1, also named TRIF) to facilitate NF-kappaB activation and type I IFN induction. It associates with PIAS1, a SUMO E3 enzyme, and Ubc9, a SUMO E2 enzyme, and plays an inhibitory role in muscle and neuronal differentiation [].ZMY11 regulates Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1)/C-terminal activation region 2 (CTAR2)-mediated NF-kappaB activation by interfering with the complex formation between TNFR-associated death domain protein (TRADD) and LMP1/CTAR2 [
,
]. It also cooperates with tumour necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) in the regulation of EBV-derived LMP1/CTAR1-induced NF-kappaB activation []. Furthermore, ZMY11 is involved in the p53-p21Cip1-mediated senescence pathway []. ZMY11 contains a plant homeodomain (PHD) finger, a bromodomain, a proline-tryptophan-tryptophan-proline (PWWP) domain, and a MYeloid translocation protein 8, Nervy and DEAF-1 (MYND) domain [
,
].
Restriction system protein Mrr-like N-terminal domain
Type:
Domain
Description:
This domain is found N-terminal to the catalytic domain in Mrr restriction endonucleases [
,
]. It is also found in other proteins, including predicted methyltransferases and ATPases. Fold recognition analysis predicts that it is a diverged member of the winged helix variant of helix turn helix proteins. It may play a role in DNA sequence recognition [
].
Members of this family are the upstream member (A) of a pair of tandem-encoded radical SAM enzymes. Most of these radical SAM gene pairs have an additional upstream regulatory gene in the MarR family. Examples of high sequence identity (over 96 percent) from cassettes in several Treponema species of the oral cavity to those in multiple Firmicutes in the gut microbiome suggest recent lateral gene transfer, as might be expected for antibiotic resistance genes. The function is unknown.
S100/Calcium binding protein 7/8-like, conserved site
Type:
Conserved_site
Description:
The calcium-binding domain found in S100, CaBP7/8 and similar proteins mainly from animals. It is a subfamily of the EF-hand calcium-binding domain [
]. S100s are small dimeric acidic calcium and zinc-binding proteins abundant in the brain, with S100B playing an important role in modulating the proliferation and differentiation of neurons and glia cells []. S100 proteins have two different types of calcium-binding sites: a low affinity one with a special structure, and a 'normal' EF-hand type high-affinity site.Protein S100-G from humans (formerly known as Calbindin-D9k) also belong to this family of proteins, but it does not form dimers. CaBP-9k is a cytosolic protein expressed in a variety of tissues. Although its precise function is unknown, it appears to be under the control of the steroid hormones oestrogen and progesterone in the female reproductive system [
]. In the intestine, this protein may be involved in calcium absorption by mediating intracellular diffusion [].Calcium-binding protein 8 from Rattus norvegicus (Rat) regulates Golgi-to-plasma membrane trafficking by interacting with PI4KB and inhibiting its activity. It may play a role in the physiology of neurons and is potentially important in memory and learning []. A number of these proteins are known to bind calcium while others are not. This entry represents the region of the EF-hand high affinity site but makes no assumptions on the calcium-binding properties of this site.
RsbT co-antagonist protein RsbRD, N-terminal domain
Type:
Domain
Description:
This domain is found at the N terminus of a number of anti-sigma-factor antagonist proteins including Bacillus subtilis RsbRD (
). These proteins are negative regulators of the general stress transcription factor sigma(B) [
].
The bluetongue virus (BTV) is a representative of the orbivirus genus of the Reoviridae. The crystal structure of VP7 from BTV serotype 10 reveals that the central one third of the polypeptide chain (residues 121-249) is folded into a β-sandwich. The rest of the polypeptide (residues 1-120 and 250-349) is composed of nine α-helices and long extended loops [
].This superfamily represents the N-terminal domain, consisting of five α-helices.
The bluetongue virus (BTV) is a representative of the orbivirus genus of the Reoviridae. The crystal structure of VP7 from BTV serotype 10 reveals that the central one third of the polypeptide chain (residues 121-249) is folded into a β-sandwich. The rest of the polypeptide (residues 1-120 and 250-349) is composed of nine α-helices and long extended loops [
].This superfamily represents the C-terminal domain consisting of four α-helices.
Uncharacterised protein family UPF0066, conserved site
Type:
Conserved_site
Description:
This conserved site is found in proteins belonging to the uncharacterised protein family UPF0066. It is found in the central part of the tsaA-like domain (
).
Transferrin-binding protein B, C-lobe handle domain
Type:
Domain
Description:
Bacterial lipoproteins represent a large group of specialized membrane proteins that perform a variety of functions including maintenance and stabilization of the cell envelope, protein targeting and transit to the outer membrane, membrane biogenesis, and cell adherence [
]. Pathogenic Gram-negative bacteria within the Neisseriaceae and Pasteurellaceae families rely on a specialized uptake system, characterized by an essential surface receptor complex that acquires iron from host transferrin (Tf) and transports the iron across the outer membrane. They have an iron uptake system composed of surface exposed lipoprotein, Tf-binding protein B (TbpB), and an integral outer-membrane protein, Tf-binding protein A (TbpA), that together function to extract iron from the host iron binding glycoprotein (Tf). TbpB is a bilobed (N and C lobe) lipid-anchored protein with each lobe consisting of an eight-stranded beta barrel flanked by a 'handle' domain made up of four (N lobe) or eight (C lobe) beta strands []. TbpB extends from the outer membrane surface by virtue of an N-terminal peptide region that is anchored to the outer membrane by fatty acyl chains on the N-terminal cysteine and is involved in the initial capture of iron-loaded Tf []. This domain family is found in the handle domain of the C lobe (domain C) of TbpB proteins. It consists of a squashed six-stranded beta sheet flanked by two antiparallel beta strands and has no supporting alpha helix as in the N lobe [
].
The bacterial protein RecR is an important regulator in the RecFOR homologous recombination pathway during DNA repair [
,
,
,
]. It acts with RecF and RecO forming a complex that facilitates the loading of RecA onto ssDNA [,
]. RecR is a zinc metalloprotein consisting of a N-terminal helix-hairpin-helix (HhH) motif, a middle region containing a zinc finger motif and a Toprim domain, and a C-terminal domain comprising a divergent Walker B motif and a C-terminal helix [,
]. This entry represents the C4-type zinc finger domain which contains four strictly conserved cysteine residues that coordinates a zinc ion [
,
]. This domain plays an important role, maintaining the stability of the 3D structure [].
Ribosomal protein S23, mitochondrial, conserved domain
Type:
Domain
Description:
This entry represents a domain found both the mitochondrial ribosomal 23S protein. The function of this conserved region is not known.In Saccharomyces cerevisiae (Baker's yeast) the mature mitochondrial ribosomes consist of a small (37S) and a large (54S) subunit. The 37S subunit contains at least 33 different proteins and 1 molecule of RNA (15S). The 54S subunit contains at least 45 different proteins and 1 molecule of RNA (21S) [
,
].
Escherichia coli has an iron(II) transport system (feo) which may make an important contribution to the iron supply of the cell under anaerobic conditions [
]. FeoB has been identified as part of this transport system. FeoB is a large 700-800 amino acid integral membrane protein. The N terminus has been previously erroneously described as being ATP-binding []. Recent work shows that it is similar to eukaryotic G-proteins and that it is a GTPase [].
Replication protein 1a, necrotic phentoype-determining domain
Type:
Domain
Description:
Replication protein 1a is a core component of the viral replicase complex in Cucumber mosaic virus and related plant viruses. 1a protein is the major virulence factor of the cucumber mosaic virus (CMV). The Ns strain of CMV causes necrotic lesions to Nicotiana spp. while other strains cause systemic mosaic [
]. This entry represents a domain within replication protein 1a that appears to determine the necrotic phenotype of the virus. This domain is found in association with
and
. Conversion of a single arginine residue within this region (Arg461) to cysteine is sufficient to convert a non-necrotic strain to a necrotic type, and vice versa [
]. Deletion of residue 461 leads to a loss of replicase activity in the 1a protein.
The first member of the FEZ (fasciculation and elongation protein zeta) family identified was unc-76, from C. elegans. The protein is necessary for normal axon fasciculation and is required for axon-axon interactions [
]. Later, two human homologues, FEZ1 and FEZ2, were identified [
]. FEZ1 and FEZ2 interact with PKCzeta and have been shown to induce neurite extension of PC12 cells when co-expressed with a constitutively active mutant of PKCzeta [].
Dispersed gene family protein 1 of Trypanosoma cruzi is likely to be highly expressed, and is expressed from the sub-telomeric region [
]. However, its function is not known. This entry represents the C-terminal domain on this protein.
Probable Brix domain-containing ribosomal biogenesis protein
Type:
Family
Description:
This entry represents archaeal sequences containing a single Brix domain. The sequences have two unique characteristics: (1) the Brix domain charged regions are totally absent at the N terminus and are reduced in number to about 10 residues at the C terminus; and (2) the C-terminal part of the Brix domain itself is minimal. Biological data for some proteins in this family suggest a role in ribosome biogenesis and rRNA binding [
,
].
Zinc binding proteins ZnuA have been shown to function as initial receptors in the ABC uptake of Zn2+. They belong to the TroA superfamily of periplasmic metal binding proteins that share a distinct fold and ligand binding mechanism. They are comprised of two globular subdomains connected by a single helix and bind their specific ligands in the cleft between these domains. A typical TroA protein is comprised of two globular subdomains connected by a single helix and can bind the metal ion in the cleft between these domains. In addition, these proteins sometimes have a low complexity region containing a metal-binding histidine-rich motif (repetitive HDH sequence) [
,
,
,
].
ABC transporters belong to the ATP-Binding Cassette (ABC) superfamily, which uses the hydrolysis of ATP to energise diverse biological systems. ABC transporters minimally consist of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These can be found on the same protein or on two different ones. Most ABC transporters function as a dimer and therefore are constituted of four domains, two ABC modules and two TMDs.ABC transporters are involved in the export or import of a wide variety of substrates ranging from small ions to macromolecules. The major function of ABC import systems is to provide essential nutrients to bacteria. They are found only in prokaryotes and their four constitutive domains are usually encoded by independent polypeptides (two ABC proteins and two TMD proteins). Prokaryotic importers require additional extracytoplasmic binding proteins (one or more per systems) for function. In contrast, export systems are involved in the extrusion of noxious substances, the export of extracellular toxins and the targeting of membrane components. They are found in all living organisms and in general the TMD is fused to the ABC module in a variety of combinations. Some eukaryotic exporters encode the four domains on the same polypeptide chain [
].The ABC module (approximately two hundred amino acid residues) is known to bind and hydrolyse ATP, thereby coupling transport to ATP hydrolysis in a large number of biological processes. The cassette is duplicated in several subfamilies. Its primary sequence is highly conserved, displaying a typical phosphate-binding loop: Walker A, and a magnesium binding site: Walker B. Besides these two regions, three other conserved motifs are present in the ABC cassette: the switch region which contains a histidine loop, postulated to polarise the attaching water molecule for hydrolysis, the signature conserved motif (LSGGQ) specific to the ABC transporter, and the Q-motif (between Walker A and the signature), which interacts with the gamma phosphate through a water bond. The Walker A, Walker B, Q-loop and switch region form the nucleotide binding site [,
,
].The 3D structure of a monomeric ABC module adopts a stubby L-shape with two distinct arms. ArmI (mainly β-strand) contains Walker A and Walker B. The important residues for ATP hydrolysis and/or binding are located in the P-loop. The ATP-binding pocket is located at the extremity of armI. The perpendicular armII contains mostly the alpha helical subdomain with the signature motif. It only seems to be required for structural integrity of the ABC module. ArmII is in direct contact with the TMD. The hinge between armI and armII contains both the histidine loop and the Q-loop, making contact with the gamma phosphate of the ATP molecule. ATP hydrolysis leads to a conformational change that could facilitate ADP release. In the dimer the two ABC cassettes contact each other through hydrophobic interactions at the antiparallel β-sheet of armI by a two-fold axis [
,
,
,
,
,
].The ATP-Binding Cassette (ABC) superfamily forms one of the largest of all protein families with a diversity of physiological functions [
]. Several studies have shown that there is a correlation between the functional characterisation and the phylogenetic classification of the ABC cassette [,
]. More than 50 subfamilies have been described based on a phylogenetic and functional classification [,
,
].The typical operon for the high affinity inorganic phosphate ABC transporter encodes an ATP-binding protein, a phosphate-binding protein, and two permease proteins. This family describes PstC, which is homologous to PstA (
). In the Escherichia coli, this transport system is induced when the concentration of extrallular inorganic phosphate is low. A constitutive, lower affinity transporter operates otherwise.
Type III secretion systems translocate proteins, usually virulence factors, out across both inner and outer membranes of certain Gram-negative bacteria and further across the plasma membrane and into the cytoplasm of the host cell. This protein, termed YscF in Yersinia, and EscF, PscF, EprI, etc. in other systems, forms the needle of the injection apparatus [
]. The structure of PscF has been revealed [,
].
Conserved hypothetical protein CHP03960, radical SAM
Type:
Family
Description:
This entry describes a radical SAM protein, or protein region, regularly found paired with or fused to a region described by
. PSI-BLAST analysis of
suggests a relationship to the tRNA pseudouridine synthase TruA, suggesting that this system may act in RNA modification.
5,10-methenyltetrahydromethanopterin hydrogenase cofactor biosynthesis protein HmdB
Type:
Family
Description:
Members of this protein family include HmdB, a partially characterised radical SAM protein with an unusual CX5CX2C motif. The colocalization of hmdB and hmdC with hmdA (which functions in the reversible reduction of methenyl-tetrahydromethanopterin to methylene-H4MPT and H+) in the genomes of hydrogenotrophic methanogens, coupled with the similar evolutionary histories observed for deduced amino acid sequences for hmdA, hmdB, and hmdC, suggests that the genes are likely involved in a common process. This argument is bolstered by the observation that homologues of HmdB and HmdC were identified only in the genomes of hydrogenotrophic methanogens that contained hmdA. The exact function of HmdB is currently not known, although it is postulated to be involved in the biosynthesis of the HMD cofactor [
].
Protein phosphatase 1 regulatory subunit 17, also known as G-substrate, is a substrate for cGMP-dependent protein kinase (PKG) and is primarily located in cerebellar Purkinje cells [
]. G-substrate phosphorylated by PKG inhibits the catalytic subunit of both protein phosphatase-1 and -2A [,
]. G-substrate regulates cerebellum-dependent long-term memory and it acts as a neuroprotectant in the ventral tegmental area and retina [].
Dihydrolipoamide acetyltransferase/Pyruvate dehydrogenase protein X component
Type:
Family
Description:
In prokaryotes and eukaryotes, pyruvate dehydrogenase complex (PDC) contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3) [
]. PDC catalyses the overall conversion of pyruvate to acetyl-CoA and CO2. In eukaryotes, PDC is located in the mitochondrial matrix [,
]. This entry represents a group of E3-binding proteins, including dihydrolipoamide acetyltransferase (E2) and pyruvate dehydrogenase protein X component (known as Pdx1). Pdx1, found only in eukaryotes, plays a structural role in the complex by binding and positioning dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide acetyltransferase (E2) core [
]. Mutations in the Pdx1 gene has been linked to human disease [,
]. Mutations in the E2 gene cause pyruvate dehydrogenase deficiency [].
This entry includes a group of pre-mRNA 3' end processing proteins, including Pfs2 from yeasts, WDR33 form animals and FY from Arabidopsis.In Saccharomyces cerevisiae, Polyadenylation factor subunit 2 (Pfs2) is an integral and essential component of the cleavage and polyadenylation factor (CPF) complex, which plays a key role in polyadenylation-dependent pre-mRNA 3'-end formation and cooperates with cleavage factors including the CFIA complex and NAB4/CFIB [
]. In animals WDR33 is part of the pre-mRNA 3' processing complex that is essential for both cleavage and polyadenylation of pre-mRNA 3' ends [
].In Arabidopsis, FY acts as an RNA 3' end-processing factor that interacts with FCA (an nuclear RNA binding protein) to control the Arabidopsis floral transition [
].
The RadB family of archaeal proteins is involved in DNA repair and in homologous recombination [
]. The proteins contain a conserved triplet of residues (Lys-His-Arg) at their C terminus that is crucial for DNA binding []. RadB does not catalyse strand exchange and does not turn over ATP efficiently. It has been shown to inhibit Holliday junction resolution by Hjc in the absence of ATP, but has little effect when ATP is present [].
Protein Z-dependent peptidase inhibitor, serpin domain
Type:
Domain
Description:
Protein Z-dependent protease inhibitor (ZPI; MEROPS identifier I04.005) is a member of the serpin superfamily of proteinase inhibitors, corresponding to clade A10 [
,
]. ZPI inhibits coagulation factor Xa, dependent on protein Z (PZ), a vitamin K-dependent plasma protein []. ZPI also inhibits factor XIa in a process that does not require PZ []. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms [].
Trafficking protein particle complex subunit TRAPPC10/Trs130
Type:
Family
Description:
The trafficking protein particle complex TRAPP is a multi-protein complex needed in the early stages of the secretory pathway. To date, two kinds of TRAPP complexes have been studied, TRAPPI and TRAPP II. These complexes differ in subunit composition [
]. TRAPP I binds vesicles derived from the endoplasmic reticulum bringing them closer to the acceptor membrane. This entry represents the TRAPPC10/Trs130 subunit of the TRAPP II complex, which functions in late Golgi trafficking as a membrane tether. TRAPPII binds the Ypt1 GTPase and probably uses the TRAPPI catalytic core to promote guanine nucleotide exchange. TRS130 plays a role in the YPT GEF activity of TRAPP II [
,
].
ATPase family AAA domain-containing protein ATAD2-like
Type:
Family
Description:
This entry represents a group of AAA domain-containing protein, including ATAD2/ATD2B from humans, Tat-binding homolog 7 from Caenorhabditis elegans (Lex-1) and Saccharomyces cerevisiae (Yta7), and ATPase with bromodomain protein abo1/2 from S. pombe.
ATPase family AAA domain-containing protein 2, also known as ANCCA, is a transcriptional coactivator for estrogen-bound estrogen receptor (ER) alpha and androgen receptor [
,
]. It is required for coregulator occupancy and chromatin modification []. ANCCA is also required for recruiting specific E2Fs to their targets and for the assembly of the HCF-MLL hKMT complex, a complex that regulates cell cycle progression []. Overexpression of ANCCA has been linked to various cancers [,
,
].In Caenorhabditis elegans, Lex-1 affects chromatin structure and promotes expression from repetitive sequences [
].In Saccharomyces cerevisiae, Yta7 binds to histones and regulates transcription of histones and other gene [
].
Uncharacterised protein family, spore photo-product lyase-related
Type:
Family
Description:
This uncharacterised radical SAM domain protein occurs rarely and sporadically in species that include select Alphaproteobacteria and Actinobacteria, and in Deinococcus deserti VCD115. It is a distant but full-length homologue to the Bacillus subtilis spore photo-product lyase (Spl), which monomerises thymine dimers created as DNA damage by UV radiation.
Protein of unknown function DUF3792, transmembrane
Type:
Family
Description:
Members of this family of strongly hydrophobic putative transmembrane protein average about 125 amino acids in length and occur mostly, but not exclusively, in the Firmicutes. Members are quite diverse in sequence. Their function is unknown.
Collagen-binding surface protein Cna-like, B-type domain
Type:
Domain
Description:
This entry represents a repeated B region domain found in the collagen-binding surface protein Cna in Staphylococcus aureus, as well as other related domains. Cna has a non-repetitive, collagen-binding A region
, followed by instances of this B region repetitive unit. The B region has one to four 23kDa repeat units (B1-B4) each with a prealbumin-like β-sandwich fold of seven strands in two sheets with a Greek key topology [
]. Each B repeat unit has two highly similar domains (D1 and D2) placed side-by-side; both D1 and D2 are included in this entry. The domain appears to form a stalk that presents the ligand binding domain away from the bacterial cell surface. Cna is a collagen-binding MSCRAMM (Microbial Surface Component Recognizing Adhesive Matrix Molecules), and is necessary and sufficient for S. aureus cells to adhere to cartilage [,
].
This entry represents the N-terminal domain of a group of proteins with unknown function. Proteins containing this domain include the YerB protein from Bacillus subtilis. YerB interacts with PcrA helicase. The interaction is not essential for cell viability or repair of UV-induced lesions [
].
Chromosome partition protein MukF, C-terminal domain
Type:
Domain
Description:
This entry represents the C-terminal domain of MukF. MukF is involved in chromosome condensation, segregation and cell cycle progression. MukE along with MukF interact with MukB in vivo forming a complex, which is required for chromosome condensation and segregation in Escherichia coli [
]. The Muk complex appears to be similar to the SMC-ScpA-ScpB complex in other prokaryotes where MukB is the homologue of SMC []. The C-terminal domain of MukF is thought to bind to MukE and MukB [].
This entry represents the middle coiled-coil domain of MukF [
]. MukF is involved in chromosome condensation, segregation and cell cycle progression. MukE along with MukF interact with MukB in vivo forming a complex, which is required for chromosome condensation and segregation in Escherichia coli []. The Muk complex appears to be similar to the SMC-ScpA-ScpB complex in other prokaryotes where MukB is the homologue of SMC [].
Chromosome partition protein MukF, winged-helix domain
Type:
Domain
Description:
This entry represents the N-terminal winged helix-turn-helix domain of MukF [
]. MukF is involved in chromosome condensation, segregation and cell cycle progression. MukE along with MukF interact with MukB in vivo forming a complex, which is required for chromosome condensation and segregation in Escherichia coli [
]. The Muk complex appears to be similar to the SMC-ScpA-ScpB complex in other prokaryotes where MukB is the homologue of SMC [].
Tumor necrosis factor alpha-induced protein 8-like
Type:
Family
Description:
Four tumor necrosis factor alpha-induced protein 8-like proteins have been identified: TNFAIP8 (also known as TIPE), TIPE1, TIPE2 and TIPE3. Overexpressed TIPE in cells can reduce cell death in vitro and increase tumor growth in vivo [
]. By contrast, TIPE2 has been demonstrated to be an inhibitor of Ras and to have a pro-apoptotic ability. TIPE1 could upregulate the pro-apoptotic members of the B-cell leukemia/lymphoma (Bcl)-2 family of proteins [].
This domain is known as VMAP-M19.
This domain represents a highly variable central region of the vWA-MoxR associated protein (VMAP) of the classical ternary system (vWA-MoxR-VMAP) in NTP-dependent conflict systems. Using sequence similarity-based clustering it has been possible to identify 29 distinct versions named VMAP-M0-28, that may be involved in sensing of invasive entities []. It is predicted to adopt an all-α-helical secondary structure.
This domain is known as VMAP-M14.
This domain represents a highly variable central region of the vWA-MoxR associated protein (VMAP) of the classical ternary system (vWA-MoxR-VMAP) in NTP-dependent conflict systems. Using sequence similarity-based clustering it has been possible to identify 29 distinct versions named VMAP-M0-28, that may be involved in sensing of invasive entities [
]. It is predicted to adopt an all-α-helical secondary structure.
This domain is known as VMAP-M8, found in actinobacteria.
This domain represents a highly variable central region of the vWA-MoxR associated protein (VMAP) of the classical ternary system (vWA-MoxR-VMAP) in NTP-dependent conflict systems. Using sequence similarity-based clustering it has been possible to identify 29 distinct versions named VMAP-M0-28, that may be involved in sensing of invasive entities [
]. It is predicted to adopt an all-α-helical secondary structure.
This domain is known as VMAP-M9, found in cyanobacteria.
This domain represents a highly variable central region of the vWA-MoxR associated protein (VMAP) of the classical ternary system (vWA-MoxR-VMAP) in NTP-dependent conflict systems. Using sequence similarity-based clustering it has been possible to identify 29 distinct versions named VMAP-M0-28, that may be involved in sensing of invasive entities [
]. It is predicted to adopt an all-α-helical secondary structure.
This domain is known as VMAP-M5.
This domain represents a highly variable central region of the vWA-MoxR associated protein (VMAP) of the classical ternary system (vWA-MoxR-VMAP) in NTP-dependent conflict systems. Using sequence similarity-based clustering it has been possible to identify 29 distinct versions named VMAP-M0-28, that may be involved in sensing of invasive entities [
]. It is predicted to adopt an all-α-helical secondary structure.
This domain is known as VMAP-M7, found in actinobacteria.This domain represents a highly variable central region of the vWA-MoxR associated protein (VMAP) of the classical ternary system (vWA-MoxR-VMAP) in NTP-dependent conflict systems. Using sequence similarity-based clustering it has been possible to identify 29 distinct versions named VMAP-M0-28, that may be involved in sensing of invasive entities [
]. It is predicted to adopt an all-α-helical secondary structure.
This domain is known as VMAP-M4, found in alpha and betaprotobacteria.
This domain represents a highly variable central region of the vWA-MoxR associated protein (VMAP) of the classical ternary system (vWA-MoxR-VMAP) in NTP-dependent conflict systems. Using sequence similarity-based clustering it has been possible to identify 29 distinct versions named VMAP-M0-28, that may be involved in sensing of invasive entities [
]. It is predicted to adopt an all-α-helical secondary structure.
This domain is known as VMAP-M2, found in actinobacteria.
This domain represents a highly variable central region of the vWA-MoxR associated protein (VMAP) of the classical ternary system (vWA-MoxR-VMAP) in NTP-dependent conflict systems. Using sequence similarity-based clustering it has been possible to identify 29 distinct versions named VMAP-M0-28, that may be involved in sensing of invasive entities [
]. It is predicted to adopt an all-α-helical secondary structure.
This domain represents VMAP-M1, predominantly found in cyanobacteria.
This domain represents a highly variable central region of the vWA-MoxR associated protein (VMAP) of the classical ternary system (vWA-MoxR-VMAP) in NTP-dependent conflict systems. Using sequence similarity-based clustering it has been possible to identify 29 distinct versions named VMAP-M0-28, that may be involved in sensing of invasive entities [
]. It is predicted to adopt an all-α-helical secondary structure.
This family includes proteins that are about 200 amino acids in length. The proteins are all from baculoviruses. This family includes ORF107 from Orgyia pseudotsugata multicapsid polyhedrosis virus (OpMNPV) and a variety of other numbered ORF proteins, such as ORF52
, ORF140
from other baculoviruses. The function of these proteins is unknown.
Protein of unknown function DUF790, endonuclease-like
Type:
Family
Description:
This family consists of several hypothetical bacterial and archaeal proteins whose functions have not been experimentally verified. Computational analysis of sequence, predicted structure and genomic context suggests that these proteins may be endonucleases involved in either restriction-modification and/or DNA excision repair [
].
Inner membrane protein YgaP-like, transmembrane domain
Type:
Domain
Description:
This entry represents a domain found in proteins from bacteria and archaea, including Inner membrane protein YgaP from Escherichia coli, a membrane protein with a rhodanese domain (
) that may have sulfurtransferase activity. YgaP adopts a dimeric assembly. This entry represents the transmembrane domain. It consist of two slightly tilted α-helices
[].
Conserved hypothetical protein CHP04013, B12-binding/radical SAM-type
Type:
Family
Description:
Members of this family have both a B12 binding homology domain and a radical SAM domain, and occur only once per genome. Some species with members of this family have a related protein with similar domain architecture. This protein is occurs largely in archaeal methanogens but also in a few bacteria, including Thermotoga maritima and Myxococcus xanthus.
DNA sulphur modification system-associated protein 4
Type:
Family
Description:
A DNA sulphur modification system, dnd (degradation during electrophoresis), is sparsely and sporadically distributed among the bacteria. Members of this protein family are strictly limited to species with the dnd operon, and are found close to the dnd operon on the chromosomes of species such as Nostoc sp. PCC 7120, Geobacter uraniireducens Rf4, and Roseobacter denitrificans OCh 114.
A key event in the regulation of the adaptive immune response is the bindingof major histocompatibility complex (MHC)-peptide complexes to T cell
antigen receptors (TCRs). The formation of such ternary complexes inducessignificant biochemical changes within T cells of the host animal. The first
detectable response of the T cell is the rapid accumulation of numeroustyrosine-phosphorylated proteins within the cell. Increased phosphotyrosine
occurs as a consequence of the activation of several different TCR-associated, hematopoietic-specific protein kinases (PTKs), thereby perturbing
the balance between those enzymes that add, and those that remove,phosphates from key tyrosine residues. These initial phosphorylation events
are required for the subsequent activation of the small guanosinetriphosphatase (GTPase) proteins Ras and Rac, the lipid kinase P13K and PLC-
gamma1. Activation of these cytoplasmic signalling proteins ultimately leadsto activation of various transcription factors (NF-AT, NF-kB, and AP-1) and
increased transcription from genes that have an important role in initiatingT cell proliferation, such as interleukin-2 (IL-2) [
].An unresolved question in the field has been which molecules and what
sequence of events tie together the early tyrosine phosphorylation eventswith the activation of these downstream signalling molecules. A likely
candidate for linking the proximal and distal portions of the TCR signallingpathway is a 36kDa transmembrane protein termed LAT. LAT becomes
phosphorylated after TCR engagement, thereby creating binding sites for theSrc homology 2 (SH2) domains of other proteins, including PLC-gamma1, Grb2,
Gads, Grap, 3BP2 and Shb. It also indirectly binds SOS, c-Cbl, Vav, SLP-76and Itk.
LAT is expressed in peripheral blood lymphocytes, thymus and spleen, as
well as in other blood cells, including megakaryocytes, platelets, naturalkiller cells and mast cells. It is excluded from the cytosol, and is found
at the plasma membrane and in the perinuclear compartment. The cellularlocalisation of LAT seems to be extremely sensitive to alternations in the
intracellular redox balance. Reduced intracellular levels of antioxidantsresult in the membrane displacement of LAT (a consequence of a
conformational change interfering with its insertion into the membrane),abrogation of TCR-mediated signalling and, consequently, hyporesponsiveness
of T lymphocytes.The amino acid sequence of LAT contains no recognised functional domains,but, consistent with its strong tyrosine phosphorylation upon TCR
stimulation, its predicted cytoplasmic tail contains 10 tyrosines, 9 ofwhich are conserved between mouse, rat and human proteins. In addition,
LAT also has 2 cysteine residues (Cys26 and Cys29 in human) that areconserved among human, rat, mouse and bovine proteins. These residues lie
proximal to the inner face of the plasma membrane: Cys26 within the TMregion and Cys29 located juxtamembrane. These membrane-proximal residues
are thought to play a vital role in LAT function. In fact, LAT is subject topost-translational palmitoylation of these residues, which appears to be
necessary to target LAT to lipid rafts in the membrane, where it can
recruit key cytosolic signalling proteins to the aggregated rafts upon TCRstimulation. Raft membrane domains are envisaged as lateral assemblies of
sphingolipids and cholesterol that form ordered membrane phases [].
Conserved hypothetical protein CHP04069, acyl carrier-related
Type:
Family
Description:
Members of this family are often related to an acyl carrier-like domain and are found in genomic contexts associated with a small Cys-rich peptide and a radical SAM protein which probably modifies the peptide.
Contractile injection systems (CISs) are cell-puncturing nanodevices that share ancestry with contractile tail bacteriophages. This entry represents the spike tip protein from a extracellular CIS present in bacteria. This protein family includes the Pvc10 (the homologue of T4 gp5.4). This monomeric protein was part of a CryoEM structure and although not resolved at atomic resolution in the map, it was observed to form the sharp conical tip on the Pvc8 spike [
].
This domain is the first, more N-terminal, C2 domain on X-linked retinitis pigmentosa GTPase regulator-interacting proteins, or RPGR-interacting proteins [
].
