| Type |
Details |
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| Protein Domain |
| Type: |
Family |
| Description: |
Bacterial GreA and GreB promote transcription elongation by stimulating an endogenous, endonucleolytictranscript cleavage activity of the RNA polymerase, allowing RNA transcription to continue past template-encoded arresting sites. GreA and GreB are sequence homologues and have homologues inevery known bacterial genome. GreA and GreB stimulate transcriptcleavage in different ways; GreA induces cleavage of 3'-RNA fragments 2-3 nt in length and can only preventthe formation of arrested complexes, whereas GreB induces cleavage of fragments up to 18 nt in length and canrescue preexisting arrested complexes [].A 15 Angstrom resolution helical reconstruction of the Escherichia coli core RNA polymerase (RNAP)/GreB complex that allows fitting of high-resolution RNAP andGreB structures. The model of the complex reveals a remarkable binding mode for GreB; the globular C-terminal domain binds RNAP at the edge of the active site channel, while the N-terminal coiled-coil domain extends 45 Angstrom into a channel directly to theRNAP active site. The results point to a key role for conserved acidic residues at the tip of the Gre factor coiled coil in modifying the RNAP active site to catalyse the transcript cleavage reaction, and mutational studies confirm that these positions are critical for Gre factor function. Functional differences between GreA and GreB correlate with the distribution of positively charged residues on one face of the N-terminal coiledcoil. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Bacterial GreA and GreB promote transcription elongation by stimulating an endogenous, endonucleolytictranscript cleavage activity of the RNA polymerase (RNAP) [], allowing RNA transcription to continue past template-encoded arresting sites. GreA and GreB are sequence homologues and have homologues inevery known bacterial genome. GreA and GreB stimulate transcriptcleavage in different ways; GreA induces cleavage of 3'-RNA fragments 2-3 nt in length and can only preventthe formation of arrested complexes, whereas GreB induces cleavage of fragments up to 18 nt in length and canrescue pre-existing arrested complexes.The 2.2 Angstrom resolution crystal structure of Escherichia coli GreA comprises an N-terminalantiparallel α-helical coiled coil, and a C-terminal globular domain. While theC-terminal domain binds RNAP, theN-terminal coiled coil interacts with the transcript 3' end and is responsible for stimulating the transcriptcleavage reaction []. Functional differences between GreA and GreB correlate with the distribution of positively charged residues onone face of the N-terminal coiled coil.Because members of the family outside the Proteobacteria resemble GreA more closely than GreB, the GreB clade () forms a plausible outgroup and the remainder of the GreA/B family, included in this family, is designated GreA. In the Chlamydias and some spirochetes, the conserved region of these proteins is found as the C-terminal region of a much larger protein. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Stathmin [](from the Greek 'stathmos' which means relay), is a ubiquitous intracellular protein, present in a variety of phosphorylated forms. It is involved in the regulation of the microtubule (MT) filament system by destabilising microtubules. It prevents assembly and promotes disassembly of microtubules []. However, when phosphorylated, its destabilisation ability is significantly reduced []. The stathmin family also includes:Stathmin 2 (Protein SCG10); a neuron-specific, membrane-associated proteinthat accumulates in the growth cones of developing neurons. It is highlysimilar in its sequence to stathmin, but differs in that it contains anadditional N-terminal hydrophobic segment of 32 residues which is probablyresponsible for its interaction with membranes.Stathmin 3 (SCG10-like protein; SCLIP) []; a protein specificallyexpressed in neurons.Stathmin 4 (Stathmin-like protein B3); which contains an additional N-terminal hydrophobic domain [].These proteins possess a stathmin-like domain (SLD) with various N-terminal extensions. SLD is a highly conserved domain of 149 amino acid residues. Structurally, it consists of an N-terminal domain of about 45 residues followed by a 78 residue α-helical domain consisting of a heptad repeat coiled coil structure and a C-terminal domain of 25 residues [, ]. The SLD binds two tubulins arranged longitudinally, head-to-tail, in protofilament-like complexes. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
Calsequestrin contains three redox inactive TRX-fold domains [, ]. This entry represents the C-terminal TRX-fold domain.Calsequestrin is the principal calcium-binding protein present in thesarcoplasmic reticulum of cardiac and skeletal muscle []. It is a highly acidic protein that is able to bind over 40 calcium ions and acts as an internalcalcium store in muscle. Sequence analysis has suggested that calcium isnot bound in distinct pockets via EF-hand motifs, but rather via presentation of a charged protein surface. Two forms of calsequestrinhave been identified. The cardiac form is present in cardiac and slowskeletal muscle and the fast skeletal form is found in fast skeletal muscle.The release of calsequestrin-bound calcium (through a a calciumrelease channel) triggers muscle contraction.The active protein is not highly structured, more than 50% ofit adopting a random coil conformation []. When calcium binds there is a structural change wherebythe α-helical content of the protein increases from 3 to 11% [].Both forms of calsequestrin are phosphorylated by casein kinase II, butthe cardiac form is phosphorylated more rapidly and to a higher degree []. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
Calsequestrin contains three redox inactive TRX-fold domains [, ]. This entry represents the middle TRX-fold domain.Calsequestrin is the principal calcium-binding protein present in thesarcoplasmic reticulum of cardiac and skeletal muscle []. It is a highly acidic protein that is able to bind over 40 calcium ions and acts as an internalcalcium store in muscle. Sequence analysis has suggested that calcium isnot bound in distinct pockets via EF-hand motifs, but rather via presentation of a charged protein surface. Two forms of calsequestrinhave been identified. The cardiac form is present in cardiac and slowskeletal muscle and the fast skeletal form is found in fast skeletal muscle.The release of calsequestrin-bound calcium (through a a calciumrelease channel) triggers muscle contraction.The active protein is not highly structured, more than 50% ofit adopting a random coil conformation []. When calcium binds there is a structural change wherebythe α-helical content of the protein increases from 3 to 11% [].Both forms of calsequestrin are phosphorylated by casein kinase II, butthe cardiac form is phosphorylated more rapidly and to a higher degree []. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
Calsequestrin contains three redox inactive TRX-fold domains [, ]. This entry represents the N-terminal TRX-fold domain.Calsequestrin is the principal calcium-binding protein present in thesarcoplasmic reticulum of cardiac and skeletal muscle []. It is a highly acidic protein that is able to bind over 40 calcium ions and acts as an internalcalcium store in muscle. Sequence analysis has suggested that calcium isnot bound in distinct pockets via EF-hand motifs, but rather via presentation of a charged protein surface. Two forms of calsequestrinhave been identified. The cardiac form is present in cardiac and slowskeletal muscle and the fast skeletal form is found in fast skeletal muscle.The release of calsequestrin-bound calcium (through a a calciumrelease channel) triggers muscle contraction.The active protein is not highly structured, more than 50% ofit adopting a random coil conformation []. When calcium binds there is a structural change wherebythe α-helical content of the protein increases from 3 to 11% [].Both forms of calsequestrin are phosphorylated by casein kinase II, butthe cardiac form is phosphorylated more rapidly and to a higher degree []. |
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
The exact function of the Hepatitis C non-structural 5A (NS5A) protein is not known, but it is an active component of the replicase, regulates replication and modulates a range of cellular processes including innate immunity and dysregulated cell growth. NS5A is organised into three domains, labelled I, II and III. Domain I contains a zinc-binding motif and an amphipathic N-terminal helix which promotes membrane association. Mutations disrupting either the membrane anchor or zinc binding are lethal for RNA replication [, ].This entry represents the 1b domain of NS5A. It consists of two distinct anti-parallel β-sheets surrounded by extensive random coil structures []. This domain contains a disulphide bond near its C-terminal not required for the RNA replicase functions of NS5A. The presence of the cited sulphide bond suggests that it is likely responsible of the structural arrangement of domains II and III, thus playing a regulatory role in NS5A function by serving as a conformation switch to modulate functions of NS5A in and out of the replicase []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Stathmin [](from the Greek 'stathmos' which means relay), is a ubiquitous intracellular protein, present in a variety of phosphorylated forms. It is involved in the regulation of the microtubule (MT) filament system by destabilising microtubules. It prevents assembly and promotes disassembly of microtubules []. However, when phosphorylated, its destabilisation ability is significantly reduced []. Stathmin is a highly conserved protein. Structurally, it consists of an N-terminal domain of about 45 residues followed by a 78 residue α-helical domain consisting of a heptad repeat coiled coil structure and a C-terminal domain of 25 residues.The stathmin family also includes:Stathmin 2 (Protein SCG10); a neuron-specific, membrane-associated proteinthat accumulates in the growth cones of developing neurons. It is highlysimilar in its sequence to stathmin, but differs in that it contains anadditional N-terminal hydrophobic segment of 32 residues which is probablyresponsible for its interaction with membranes.Stathmin 3 (SCG10-like protein; SCLIP) []; a protein specificallyexpressed in neurons.Stathmin 4 (Stathmin-like protein B3); which contains an additional N-terminal hydrophobic domain [].This entry represents stathmin-2 (also known as SCG10). |
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| Protein Domain |
| Type: |
Family |
| Description: |
The TCR complex of T-lymphocytes consists of either a TCR alpha/beta or TCR gamma/delta heterodimer co-expressed at the cell surface with the invariant subunits of CD3 labelled gamma, delta, epsilon, zeta, and eta []. The zeta subunit forms either homodimers or heterodimers with eta [], but eta homodimers have not been observed. The structure of the zetazeta transmembrane dimer consists of a left-handed coiled coil with polar contacts. Two aspartic acids are critical for zetazeta dimerisation and assembly with TCR []. The high affinity immunoglobulin epsilon receptor (IgE Fc receptor) subunit gamma associates with a variety of FcR alpha chains to form a functional signaling complex. The gamma subunit has a critical role in allowing the IgE Fc receptor to reach the cell surface and regulates several aspects of the immune response []. It has significant structural homology to CD3 zeta and the related CD3 eta subunit and can facilitate T cell receptor expression and signaling in the absence of CD3 zeta and CD3 eta [].This family includes both CD3 zeta subunits and IgE Fc receptor gamma subunits. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
The subfamily Paramyxovirinae of the family Paramyxoviridae now contains as main genera the Rubulaviruses, avulaviruses, respiroviruses, Henipavirus-es and morbilliviruses. Protein P is the best characterised, structurally of the replicative complex of N, P and L proteins and consists of two functionally distinct moieties, an N-terminal PNT, and a C-terminal PCT []. The P protein is an essential part of the viral RNA polymerase complex formed from the P and L proteins []. P protein plays a crucial role in the enzyme by positioning L onto the N/RNA template through an interaction with the C-terminal domain of N. Without P, L is not functional.The C-terminal part of P (PCT) is only functional as an oligomer and forms with L the polymerase complex. PNT is poorly conserved and unstructured in solution while PCT contains the oligomerisation domain (PMD) that folds as a homotetrameric coiled coil containing the L binding region and a C-terminal partially folded domain, PX (residues 474 to 568), identified as the nucleocapsid binding site. Interestingly, PX is also expressed as an independent polypeptide in infected cells. PX has a C-subdomain (residues 516 to 568) that consists of three {alpha}-helices arranged in an antiparallel triple-helical bundle linked to an unfolded flexible N-subdomain (residues 474 to 515). |
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
Stathmin [](from the Greek 'stathmos' which means relay), is a ubiquitous intracellular protein, present in a variety of phosphorylated forms. It is involved in the regulation of the microtubule (MT) filament system by destabilising microtubules. It prevents assembly and promotes disassembly of microtubules []. However, when phosphorylated, its destabilisation ability is significantly reduced []. The stathmin family also includes:Stathmin 2 (Protein SCG10); a neuron-specific, membrane-associated proteinthat accumulates in the growth cones of developing neurons. It is highlysimilar in its sequence to stathmin, but differs in that it contains anadditional N-terminal hydrophobic segment of 32 residues which is probablyresponsible for its interaction with membranes.Stathmin 3 (SCG10-like protein; SCLIP) []; a protein specificallyexpressed in neurons.Stathmin 4 (Stathmin-like protein B3); which contains an additional N-terminal hydrophobic domain [].These proteins possess a stathmin-like domain (SLD) with various N-terminal extensions. SLD is a highly conserved domain of 149 amino acid residues. Structurally, it consists of an N-terminal domain of about 45 residues followed by a 78 residue α-helical domain consisting of a heptad repeat coiled coil structure and a C-terminal domain of 25 residues [, ]. The SLD binds two tubulins arranged longitudinally, head-to-tail, in protofilament-like complexes. |
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
The bacteriophage baseplate controls host cell recognition, attachment, tail sheath contraction and viral DNA ejection. The baseplate is a multi-subunit assembly at the distal end of the tail, which is composed of long and short tail fibres []. The tail region is responsible for attachment to the host bacteria during infection: long tail fibres enable host receptor recognition, while irreversible attachment is via short tail fibres. Recognition and attachment induce a conformational transition of the baseplate from a hexagonal to a star-shaped structure. In viruses such as Bacteriophage T4, Gp11 acts as a structural protein to connect the short tail fibres to the baseplate, while Gp9 connects the baseplate with the long tail fibres. Both Gp9 and Gp11 are trimers. Each Gp11 monomer consists of three domains, which are entwined together in the trimer: the N-terminal domains of the three monomers form a central, trimeric, parallel coiled coil surrounded by the entwined middle finger domains; the C-terminal domains appear to be responsible for trimerisation []. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
Ketol-acid reductoisomerase (KARI; ()), also known as acetohydroxyacid isomeroreductase (AHIR or AHAIR), catalyzes the conversion ofacetohydroxy acids into dihydroxy valerates in the second step of thebiosynthetic pathway for the essential branched-chain amino acids valine,leucine, and isoleucine. KARI catalyzes an unusual two-step reactionconsisting of an alkyl migration in which the substrate, either 2-acetolactate(AL) or 2-aceto-2-hydroxybutarate (AHB), is converted to 3-hydoxy-3-methyl-2-oxobutyrate or 3-hydoxy-3-methyl-2-pentatonate, followed by a NADPH-dependentreduction to give 2,3-dihydroxy-3-isovalerate or 2,3-dihydroxy-3-methylvalerate respectively [, , , , , ].KARI is present only in bacteria, fungi, and plants, but not in animals. KARIsare divided into two classes on the basis of sequence length andoligomerization state. Class I KARIs are ~340 amino acid residues in lengthand include all fungal KARIs, whereas class II KARIs are ~490 residues longand include all plant KARIs. Bacterial KARIs can be either class I or classII. KARIs are composed of two types of domains, an N-terminal Rossmann folddomain and one or two C-terminal knotted domains. Two intertwinned knotteddomains are required for function, and in the short-chain or class I KARIs,each polypeptide chain has one knotted domain. As a result, dimerization oftwo monomers forms two complete KARI active sites. In the long-chain or classII KARIs, a duplication of the knotted domain has occurred and, as a result,the protein does not require dimerization to complete its active site[, , , , , ].The α-helical KARI C-terminal knotted domain can be described as a six-helix core in which helices coil like cable threads around each other, thusforming a bundle [, , , , ]. |
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| Protein Domain |
| Type: |
Repeat |
| Description: |
Clathrin is a triskelion-shaped cytoplasmic protein that polymerises into a polyhedral lattice on intracellular membranes to form protein-coated membrane vesicles. Lattice formation induces the sorting of membrane proteins during endocytosis and organelle biogenesis by interacting with membrane-associated adaptor molecules. Clathrin functions as a trimer, and these trimers, or triskelions, are comprised of three legs joined by a central vertex. Each leg consists of one heavy chain and one light chain. The clathrin heavy-chain contains a 145-residue repeat that is present in seven copies [, ]. The clathrin heavy-chain repeat (CHCR) is also found in nonclathrin proteins such as Pep3, Pep5, Vam6, Vps41, and Vps8 from Saccharomyces cerevisiae and their orthologs from other eukaryotes [, , , ]. These proteins, like clathrins, are involved in vacuolar maintenance and protein sorting. The CHCR repeats in these proteins could mediate protein-protein interactions, or possibly represent clathrin-binding domains, or perform clathrin-like functions. CHCR repeats in the clathrin heavy chain, Saccharomyces cerevisiae Vamp2 and human Vamp6 have been implicated in homooligomerization, suggesting that this may be the primary function of this repeat.The CHCR repeat folds into an elongated right-handed superhelix coil of short α-helices []. Individual 'helix-turn-helix-loop' or helix hairpin units comprise the canonical repeat and stack along the superhelix axis to form a single extended domain. The canonical hairpin repeat of the clathrin superhelix resembles a tetratrico peptide repeat (TPR), but is shorter and lacks the characteristic spacing of the hydrophobic residues in TPRs. |
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
This entry represents the oligomerisation domain of the breakpoint cluster region oncoprotein Bcr, and the Bcr/Abl (Abelson-leukemia-virus) fusion protein created by a reciprocal (9;22) fusion []. Brc displays serine/threonine protein kinase activity (), acting as a GTPase-activating protein for RAC1 and CDC42. Brc promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them []. The Bcr/Abl fusion protein loses some of the regulatory function of Bcr with regards to small Rho-like GTPases with negative consequences on cell motility, in particular on the capacity to adhere to endothelial cells [].The Bcr, Bcr/Abl oncoprotein oligomerisation domain consists of a short N-terminal helix (alpha-1), a flexible loop and a long C-terminal helix (alpha-2). Together these form an N-shaped structure, with the loop allowing the two helices to assume a parallel orientation. The monomeric domains associate into a dimer through the formation of an antiparallel coiled coil between the alpha-2 helices and domain swapping of two alpha-1 helices, where one alpha-1 helix swings back and packs against the alpha-2 helix from the second monomer. Two dimers then associate into a tetramer. The oligomerisation domain is essential for the oncogenicity of the Bcr-Abl protein []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Structural maintenance of chromosomes protein 1A (SMC1A) is a homologue of the yeast Smc1 protein, which is a component of the cohesin complex required for sister chromatid cohesion []. In human, it is part of the core cohesion complex composed of SMC1A, SMC3, RAD21 and STAG proteins []. These proteins form a ring structure that encircles sister chromatids to mediate sister chromatid cohesion []. SMC1A binds to SMC3 through its hinge domain []. Besides sister chromatid cohesion function, SMC1A-SMC3 heterodimer can also found in the RC-1 complex, a mammalian protein complex that promotes repair of DNA gaps and deletions through recombination [, ]. This entry also includes Smc1 homologue from Caenorhabditis elegans, SMCL-1. Unlike canonical SMC proteins, SMCL-1 lacks hinge and coil domains, and its ATPase domain lacks conserved amino acids required for ATP hydrolysis []. Mutations in SMC1A gene cause Cornelia de Lange syndrome 2 (CDLS2), which is a form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems [, ]. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
CheR proteins are part of the chemotaxis signaling mechanism in bacteria. Flagellated bacteria swim towards favourable chemicals and away from deleterious ones. Sensing of chemoeffector gradients involves chemotaxis receptors, transmembrane (TM) proteins that detect stimuli through their periplasmic domains and transduce the signals via their cytoplasmic domains []. Signalling outputs from these receptors are influenced both by the binding of the chemoeffector ligand to their periplasmic domains and by methylation of specific glutamate residues on their cytoplasmic domains. Methylation is catalysed by CheR, an S-adenosylmethionine-dependent methyltransferase [], which reversibly methylates specific glutamate residues within a coiled coil region, to form gamma-glutamyl methyl ester residues [, ].The structure of the Salmonella typhimurium chemotaxis receptor methyltransferase CheR, bound to S-adenosylhomocysteine, has been determined to a resolution of 2.0 A []. The structure reveals CheR to be a two-domain protein, with a smaller N-terminal helical domain linked via a single polypeptide connection to a larger C-terminal alpha/beta domain. The C-terminal domain has the characteristics of a nucleotide-binding fold, with an insertion of a small anti-parallel β-sheet subdomain. The S-adenosylhomocysteine-binding site is formed mainly by the large domain, with contributions from residues within the N-terminal domain and the linker region []. |
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
Antifreeze proteins (AFPs) are a class of proteins that are able to bind to and inhibit the growth of macromolecular ice, thereby permitting an organism to survive subzero temperatures by decreasing the probability of ice nucleation in their bodies []. These proteins have been characterised from a variety of organisms, including fish, plants, bacteria, fungi and arthropods. This entry represents insect AFPs of the type found in spruce budworm, Choristoneura fumiferana.The structure of these AFPs consists of a left-handed β-helix with 15 residues per coil []. The β-helices of insect AFPs present a highly rigid array of threonine residues and bound water molecules that can effectively mimic the ice lattice. As such, β-helical AFPs provide a more effective coverage of the ice surface compared to the α-helical fish AFPs.A second insect antifreeze from Tenebrio molitor () also consists of β-helices, however in these proteins the helices form a right-handed twist; these proteins show no sequence homology to the current entry, but may act by a similar mechanism. The β-helix motif may be used as an AFP structural motif in non-homologous proteins from other (non-fish) organisms as well. |
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
Many microorganisms, such as methanogenic, acetogenic, nitrogen-fixing, photosynthetic, or sulphate-reducing bacteria, metabolise hydrogen. Hydrogen activation is mediated by a family of enzymes, termed hydrogenases, which either provide these organisms with reducing power from hydrogen oxidation, or act as electron sinks. There are two hydrogenases families that differ functionally from each other: NiFe hydrogenases tend to be more involved in hydrogen oxidation, while Iron-only FeFe (Fe only) hydrogenases in hydrogen production. Fe only hydrogenases () can either be monomeric and cytoplasmic or heterodimeric and periplasmic, being involved in either hydrogen production or uptake, respectively. This entry represents the small subunit of the heterodimeric enzyme, which is comprised of alternating random coil and alpha helical structures that encompass the large subunit in a novel protein fold [].A domain homologous to the small subunit is found at the C terminus of iron-only hydrogenase-like protein 1 (IOP1) and IOP2 (also known as nuclear prelamin A recognition factor), two orthologue proteins found in mammalian cells. IOP1 has been shown to be involved in mammalian cytosolic Fe-S protein maturation []. |
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
CheR proteins are part of the chemotaxis signaling mechanism in bacteria. Flagellated bacteria swim towards favourable chemicals and away from deleterious ones. Sensing of chemoeffector gradients involves chemotaxis receptors, transmembrane (TM) proteins that detect stimuli through their periplasmic domains and transduce the signals via their cytoplasmic domains []. Signalling outputs from these receptors are influenced both by the binding of the chemoeffector ligand to their periplasmic domains and by methylation of specific glutamate residues on their cytoplasmic domains. Methylation is catalysed by CheR, an S-adenosylmethionine-dependent methyltransferase [], which reversibly methylates specific glutamate residues within a coiled coil region, to form gamma-glutamyl methyl ester residues [, ].The structure of the Salmonella typhimurium chemotaxis receptor methyltransferase CheR, bound to S-adenosylhomocysteine, has been determined to a resolution of 2.0 A []. The structure reveals CheR to be a two-domain protein, with a smaller N-terminal helical domain linked via a single polypeptide connection to a larger C-terminal alpha/beta domain. The C-terminal domain has the characteristics of a nucleotide-binding fold, with an insertion of a small anti-parallel β-sheet subdomain. The S-adenosylhomocysteine-binding site is formed mainly by the large domain, with contributions from residues within the N-terminal domain and the linker region []. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
CheR proteins are part of the chemotaxis signaling mechanism in bacteria. Flagellated bacteria swim towards favourable chemicals and away from deleterious ones. Sensing of chemoeffector gradients involves chemotaxis receptors, transmembrane (TM) proteins that detect stimuli through their periplasmic domains and transduce the signals via their cytoplasmic domains []. Signalling outputs from these receptors are influenced both by the binding of the chemoeffector ligand to their periplasmic domains and by methylation of specific glutamate residues on their cytoplasmic domains. Methylation is catalysed by CheR, an S-adenosylmethionine-dependent methyltransferase [], which reversibly methylates specific glutamate residues within a coiled coil region, to form gamma-glutamyl methyl ester residues [, ].The structure of the Salmonella typhimurium chemotaxis receptor methyltransferase CheR, bound to S-adenosylhomocysteine, has been determined to a resolution of 2.0 A []. The structure reveals CheR to be a two-domain protein, with a smaller N-terminal helical domain linked via a single polypeptide connection to a larger C-terminal alpha/beta domain. The C-terminal domain has the characteristics of a nucleotide-binding fold, with an insertion of a small anti-parallel β-sheet subdomain. The S-adenosylhomocysteine-binding site is formed mainly by the large domain, with contributions from residues within the N-terminal domain and the linker region []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
LRP chaperone MESD (also known as mesoderm development candidate 2) represents a set of highly conserved proteins found from nematodes to humans. It is a chaperone that specifically assists with the folding of β-propeller/EGF modules within the family of low-density lipoprotein receptors (LDLRs). It also acts as a modulator of the Wnt pathway, since some LDLRs are coreceptors for the canonical Wnt pathway and is essential for specification of embryonic polarity and mesoderm induction []. The Drosophila homologue, known as boca, is an endoplasmic reticulum protein required for wingless signaling and trafficking of LDL receptor family members [].The final C-terminal residues, KEDL, are the endoplasmic reticulum retention sequence as it is an ER protein specifically required for the intracellular trafficking of members of the low-density lipoprotein family of receptors (LDLRs) []. The N- and C-terminal sequences are predicted to adopt a random coil conformation, with the exception of an isolated predicted helix within the N-terminal region, The central folded domain flanked by natively unstructured regions is the necessary structure for facilitating maturation of LRP6 (Low-Density Lipoprotein Receptor-Related Protein 6 Maturation) []. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
This is the N-terminal region of MukB. MukB is involved in the segregation and condensation of prokaryotic chromosomes. 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 []. ScpA () and ScpB () have little sequence similarity to MukE or MukF, though they are predicted to be structurally similar, being predominantly α-helical with coiled coil regions. The structure of the N-terminal domain consists of an antiparallel six-stranded beta sheet surrounded by one helix on one side and by five helices on the other side []. It contains an exposed Walker A loop in an unexpected helix-loop-helix motif. In other proteins, Walker A motifs generally adopt a P loop conformation as part of a strand-loop-helix motif embedded in a conserved topology of alternating helices and (parallel) beta strands []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2), also known as MAYP, belongs to the PCH (Pombe Cdc15 homology) family of proteins involved in the regulation of actin-related functions, including cell adhesion and motility []. In mice, it regulates F-actin bundling and enhances filopodia formation and motility in macrophages []. It may play an anti-inflammatory role in macrophages [].Pombe Cdc15 homology (PCH) family proteins were initially identified as adaptor proteins involved in the regulation of cytokinesis and actin dynamics []. They share a similar domain architecture, consisting of an N-terminal FCH domain followed by a coiled coil (CC) region and by one or two C-terminal SH3 domains. However, in some family members the SH3 domain is absent (FCHO1, FCHO2 and PSTPIP2) or there are tissue-specific alternatively spliced isoforms with and without an SH3 domain (CIP4b, CIP4c, CIP4V, Fbp17b). PCH family proteins interact with receptors, adaptors, enzymes and structural proteins to regulate their localisation and activity. Through these interactions, PCH proteins regulate cell morphology and motility, organelle integrity, protein trafficking and the organisation of the actin cytoskeleton []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
This family represents ScpB, which along with ScpA () interacts with SMC in vivo forming a complex that is required for chromosome condensation and segregation [, ]. The SMC-Scp complex appears to be similar to the MukB-MukE-Muk-F complex in Escherichia coli [], where MukB () is the homologue of SMC. ScpA and ScpB have little sequence similarity to MukE () or MukF (), they are predicted to be structurally similar, being predominantly α-helical with coiled coil regions. In general scpA and scpB form an operon in most bacterial genomes. Flanking genes are highly variable suggesting that the operon has moved throughout evolution. Bacteria containing an smc gene also contain scpA or scpB but not necessarily both. An exception is found in Deinococcus radiodurans, which contains scpB but neither smc nor scpA. In the archaea the gene order SMC-ScpA is conserved in nearly all species, as is the very short distance between the two genes, indicating co-transcription of the both in different archaeal genera and arguing that interaction of the gene products is not confined to the homologues in Bacillus subtilis. It would seem probable that, in light of all the studies, SMC, ScpA and ScpB proteins or homologues act together in chromosome condensation and segregation in all prokaryotes []. |
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
This superfamily represents a subdomain known as domain D found at the C terminus of Tip20, which is part of the Dsl1p vesicle tethering complex essential for trafficking from the Golgi apparatus to the ER. The structure of Tip20p consists entirely of α-helices and intervening loops of variable length, organised into a series of helix bundle domains []. Subunits of the vesicle tethering complex (such as Tip20 and Dsl1) share protein sequence similarity with known subunits of the exocyst complex, establishing a structural connection among several multi-subunit tethering complexes and implying that many of their subunits are derived from a common progenitor. Proteins containing this domain includes EXOC6/PINT-1 from animals, Tip20 from budding yeast, Sec15 from fission yeasts and MAIGO2 (Mag2) from plants. Sec15 (EXOC6 homologue) is an exocyst complex component that links Sec4 and downstream fusion effectors at discrete cellular locations. Its C-terminal domain mediates Rab GTPases binding which occurs in a GTP-dependent manner []. PINT-1/Tip20/MAIGO2 play a role in anterograde transport from the endoplasmic reticulum (ER) to the Golgi and/or retrograde transport from the Golgi to the ER. They share a similar domain organisation with an N-terminal leucine heptad repeat rich coiled coil and an ~500-residue C-terminal RINT1/TIP20 domain, which might be a protein-protein interaction module necessary for the formation of functional complexes. |
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
Subunits of the vesicle tethering complex (such as Tip20 and Dsl1) share protein sequence similarity with known subunits of the exocyst complex, establishing a structural connection among several multi-subunit tethering complexes and implying that many of their subunits are derived from a common progenitor. Proteins containing this domain includes EXOC6/PINT-1 from animals, Tip20 from budding yeast, Sec15 from fission yeasts and MAIGO2 (Mag2) from plants. Sec15 (EXOC6 homologue) is an exocyst complex component that links Sec4 and downstream fusion effectors at discrete cellular locations. Its C-terminal domain mediates Rab GTPases binding which occurs in a GTP-dependent manner []. PINT-1/Tip20/MAIGO2 play a role in anterograde transport from the endoplasmic reticulum (ER) to the Golgi and/or retrograde transport from the Golgi to the ER. They share a similar domain organisation with an N-terminal leucine heptad repeat rich coiled coil and an ~500-residue C-terminal RINT1/TIP20 domain, which might be a protein-protein interaction module necessary for the formation of functional complexes. This superfamily represents the domain 1 found in the C-terminal domain of the exocyst complex subunit Sec15. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Antifreeze proteins (AFPs) are a class of proteins that are able to bind to and inhibit the growth of macromolecular ice, thereby permitting an organism to survive subzero temperatures by decreasing the probability of ice nucleation in their bodies []. These proteins have been characterised from a variety of organisms, including fish, plants, bacteria, fungi and arthropods. This entry represents insect AFPs of the type found in spruce budworm, Choristoneura fumiferana.The structure of these AFPs consists of a left-handed β-helix with 15 residues per coil []. The β-helices of insect AFPs present a highly rigid array of threonine residues and bound water molecules that can effectively mimic the ice lattice. As such, β-helical AFPs provide a more effective coverage of the ice surface compared to the α-helical fish AFPs.A second insect antifreeze from Tenebrio molitor () also consists of β-helices, however in these proteins the helices form a right-handed twist; these proteins show no sequence homology to the current entry, but may act by a similar mechanism. The β-helix motif may be used as an AFP structural motif in non-homologous proteins from other (non-fish) organisms as well. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
Tripartite motif-containing protein 63 (TRIM63), also known as MURF-1 is an E3 ubiquitin-protein ligase involved in ubiquitin-mediated muscle protein turnover [, ]. It is predominantly fast (type II) fibre-associated in skeletal muscle and can bind to many myofibrillar proteins, including titin, nebulin, the nebulin-related protein NRAP, troponin-I (TnI), troponin-T (TnT), myosin light chain 2 (MLC-2), myotilin, and T-cap. The early and robust upregulation of MuRF-1 is triggered by disuse, denervation, starvation, sepsis, or steroid administration resulting in skeletal muscle atrophy. It also plays a role in maintaining titin M-line integrity []. It associates with the periphery of the M-line lattice and may be involved in the regulation of the titin kinase domain []. It also participates in muscle stress response pathways and gene expression [, ]. MuRF-1 belongs to the C-II subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain. It also harbours a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains [].This entry represents the C3HC4-type RING-HC finger found in TRIM63. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
Members of the TCP family of transcription factors have so far only been found in plants, where they are implicated in processes related to cell proliferation. It appears that TCP domain (see ) protein have been recruited during evolution to control cell division and growth in various developmental processes. The TCP proteins fall into two subfamilies, one including CYC and TB1 and the other including the PCFs. Most members of the CYC/TB1 subfamily have an R domain, predicted to form a coiled coil that may mediate protein-protein interactions [, ].The R domain is rich in polar residues (arginine, lysine and glutamic acid) and is predicted to form a hydrophilic α-helix [].Some proteins known to contain an R domain are listed below:Antirrhinum majus (Garden snapdragon) cycloidea (CYC). It is involved in the control of floral symmetry, a character that has changed many times during plant evolutionZea mays (Maize) teosinte branched 1 (TB1). It controls the developmental of apical dominance that contributed to the evolution of modern day maize from its wild ancestor teosinte Arabidopsis thaliana (Mouse-ear cress) TCP2 and TCP3, which correlate with actively dividing regions of the floral meristem |
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
This superfamily represents a structural domain which consists of three α-helices, including the arfaptin homology (AH) domain and the BAR (Bin-Amphiphysin-Rvs) domain.The arfaptin homology (AH) domain is a protein domain found in a range of proteins, including arfaptins, protein kinase C-binding protein PICK1 []and mammalian 69kDa islet cell autoantigen (ICA69) []. The AH domain of arfaptin has been shown to dimerise and to bind Arf and Rho family GTPases [, ], including ARF1, a small GTPase involved in vesicle budding at the Golgi complex and immature secretory granules. The AH domain consists of three α-helices arranged as an extended antiparallel α-helical bundle. Two arfaptin AH domains associate to form a highly elongated, crescent-shaped dimer [, ].Members of the Amphiphysin protein family are key regulators in the early steps of endocytosis, involved in the formation of clathrin-coated vesicles by promoting the assembly of a protein complex at the plasma membrane and directly assist in the induction of the high curvature of the membrane at the neck of the vesicle. Amphiphysins contain a characteristic domain, known as the BAR (Bin-Amphiphysin-Rvs) domain, which is required for their in vivofunction and their ability to tubulate membranes []. The crystal structure of these proteins suggest the domain forms a crescent-shaped dimer of a three-helix coiled coil with a characteristic set of conserved hydrophobic, aromatic and hydrophilic amino acids. Proteins containing this domain have been shown to homodimerise, heterodimerise or, in a few cases, interact with small GTPases. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
TIF1-beta, also known as Kruppel-associated Box (KRAB)-associated protein 1 (KAP-1), belongs to the C-VI subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a plant homeodomain (PHD), and a bromodomain (Bromo) positioned C-terminal to the RBCC domain. It acts as a nuclear co-repressor that plays a role in transcription and in the DNA damage response [, , ]. Upon DNA damage, the phosphorylation of KAP-1 on serine 824 by the ataxia telangiectasia-mutated (ATM) kinase enhances cell survival and facilitates chromatin relaxation and heterochromatic DNA repair []. It also regulates CHD3 nucleosome remodelling during the DNA double-strand break (DSB) response []. Meanwhile, KAP-1 can be dephosphorylated by protein phosphatase PP4C in the DNA damage response []. Moreover, KAP-1 is a co-activator of the orphan nuclear receptor NGFI-B (or Nur77) and is involved in NGFI-B-dependent transcription []. It is also a coiled-coil binding partner, substrate and activator of the c-Fes protein tyrosine kinase []. The N-terminal RBCC domains of TIF1-beta are responsible for the interaction with KRAB zinc finger proteins (KRAB-ZFPs), MDM2, MM1, C/EBPbeta, and the regulation of homo- and heterodimerization []. The C-terminal PHD/Bromo domains are involved in interacting with SETDB1, Mi-2alpha and other proteins to form complexes with histone deacetylase or methyltransferase activity [, ].This entry represents the RING-HC finger found in TIF1-beta. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
TRIM54, also known as MuRF-3, is an E3 ubiquitin-protein ligase involved in ubiquitin-mediated muscle protein turnover. It is ubiquitously detected in all fibre types, and is developmentally upregulated, associates with microtubules, the sarcomeric M-line (this report) and Z-line, and is required for microtubule stability and myogenesis. It associates with glutamylated microtubules during skeletal muscle development, and is required for skeletal myoblast differentiation and development of cellular microtubular networks. MuRF-3 controls the degradation of four-and-a-half LIM domain (FHL2) and gamma-filamin and is required for maintenance of ventricular integrity after myocardial infarction (MI) [, , ]. MuRF-3 belongs to the C-II subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain. It also harbours a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains.This entry represents the C3HC4-type RING-HC finger found in MuRF-3 (TRIM54). |
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| Protein Domain |
| Type: |
Domain |
| Description: |
Several proteins that contain RING fingers also contain a well-conserved40-residue cysteine-rich domain termed a B-box zinc finger. Often, one or two copies of the B-box are associated with a coiled coil domain in additionto the ring finger, forming a tripartite motif. The tripartite motif is found in transcription factors, ribonucleoproteins and proto-oncoproteins,but no function has yet been ascribed to the domain [].The solution structure of the B-box motif has been determined by NMR. The protein is a monomer, with 2 β-strands, 2 helical turns and 3extended loop regions packed in a novel topology []. Of 7 potential zincligands, only 4 are used, binding a single zinc atom in a C2-H2 tetrahedral arrangement. The B-box structure differs in tertiary fold from allother known zinc-binding motifs.A group of proteins that contain the B-box motif also host a well conserveddomain of unknown function. Proteins that include this domain are,e.g.: butyrophilin, the RET finger protein, the 52kDa Ro protein and theXenopus nuclear factor protein. The C-terminal portion of this region hasbeen termed the SPRY domain (after SPla and the RYanodine Receptor) []. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
This entry represents the SH3 domain of proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1).Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) belongs to the PCH family. It interacts with Wiskott-Aldrich syndrome protein (WASP) and PTPN12, which are important regulators of the cytoskeleton and cell migration, suggesting that PSTPIP1 functions in these pathways []. PSTPIP1 has been identified as a component of the leukocyte uropod that regulates endocytosis and cell migration []. It also controls extracellular matrix degradation and filopodia formation in macrophages []. It interacts with pyrin, a protein that associates with the cytoskeleton in myeloid/monocytic cells and modulates IL-1beta processing, NF-kappaB activation, and apoptosis []. Mutations in the PSTPIP1 gene have been linked to PAPA syndrome, an inflammatory disease [].Pombe Cdc15 homology (PCH) family proteins were initially identified as adaptor proteins involved in the regulation of cytokinesis and actin dynamics []. They share a similar domain architecture, consisting of an N-terminal FCH domain followed by a coiled coil (CC) region and by one or two C-terminal SH3 domains. However, in some family members the SH3 domain is absent (FCHO1, FCHO2 and PSTPIP2) or there are tissue-specific alternatively spliced isoforms with and without an SH3 domain (CIP4b, CIP4c, CIP4V, Fbp17b). PCH family proteins interact with receptors, adaptors, enzymes and structural proteins to regulate their localisation and activity. Through these interactions, PCH proteins regulate cell morphology and motility, organelle integrity, protein trafficking and the organisation of the actin cytoskeleton []. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
This entry represents the oligomerisation domain of the breakpoint cluster region oncoprotein Bcr, and the Bcr/Abl (Abelson-leukemia-virus) fusion protein created by a reciprocal (9;22) fusion []. Brc displays serine/threonine protein kinase activity (), acting as a GTPase-activating protein for RAC1 and CDC42. Brc promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them []. The Bcr/Abl fusion protein loses some of the regulatory function of Bcr with regards to small Rho-like GTPases with negative consequences on cell motility, in particular on the capacity to adhere to endothelial cells [].The Bcr, Bcr/Abl oncoprotein oligomerisation domain consists of a short N-terminal helix (alpha-1), a flexible loop and a long C-terminal helix (alpha-2). Together these form an N-shaped structure, with the loop allowing the two helices to assume a parallel orientation. The monomeric domains associate into a dimer through the formation of an antiparallel coiled coil between the alpha-2 helices and domain swapping of two alpha-1 helices, where one alpha-1 helix swings back and packs against the alpha-2 helix from the second monomer. Two dimers then associate into a tetramer. The oligomerisation domain is essential for the oncogenicity of the Bcr-Abl protein []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
AAA proteases are ATP-dependent metallopeptidases present in eubacteria as well as in organelles of bacterial origin, i.e., mitochondria and chloroplasts. The AAA proteases are also known as FtsH, referring to the Escherichia coli enzyme (Filamentous temperature sensitive H). Most bacteria have a single gene encoding FtsH, three genes are present in yeast and humans, while 12 orthologs have been found in the genome of plants [].E. coil FtsH is a membrane-anchored ATP-dependent protease that degrades misfolded or misassembled membrane proteins as well as a subset of cytoplasmic regulatory proteins. FtsH is a 647-residue protein of 70kDa, with two putative transmembrane segments towards its N terminus which anchor the protein to the membrane, giving rise to a periplasmic domain of 70 residues and a cytoplasmic segment of 520 residues containing the ATPase and protease domains [].The main function of organellar AAA/FtsH proteases is selective degradation of non-assembled, incompletely assembled and/or damaged membrane-anchored proteins. Additional functions of the AAA/FtsH proteases that are not directly connected with protein quality control are processing of pre-proteins, dislocation of membrane proteins or degradation of regulatory proteins [, , ]. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
N-terminal RING finger/B-box/coiled coil (RBCC) or tripartite motif (TRIM) proteins, which are found in metazoa, are involved in a vast array of intracellular functions. They appear to function as part of large protein complexes and possess ubiquitin-protein isopeptide ligase activity. The following RBCC proteins contain an ~60-residue COS (C-terminal subgroup one signature) domain, which is also found in a distantly related non-RBCC microtubule-binding protein, GLFND:Vertebrate MID1 and MID2, which associate with microtubules through homo- and heterodimerizationAnimal TRIM9, which plays a regulatory role in synaptic vesicle exocytosisMammalian TRIM nine-like (TNL)Mammalian TRIM36, which could play a regulatory role in exocytosis of the sperm vesicleMammalian tripartite, fibronectin type III and C-terminal B30.2/SPRY (TRIFIC)Mammalian muscle-specific RING finger (MURF) family. MURF proteins have an ability to form both homo- and heterodimers with each other and to associate with the microtubule cytoskeletonIn addition to RBCC, the COS domain is also found in association with B30.2/SPRY or fibronectin type-III (FN3) domains.The COS domain is predicted to consist of two α-helical coils []. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
The C-CAP/cofactor C-like domain is present in several cytoskeleton-related proteins, which also contain a number of additional domains [, , , ]:Eukaryotic cyclase-associated protein (CAP or SRV2), a modular actin monomer binding that directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localisation and the establishment of cell polarity.Vertebrate retinitis pigmentosa 2 (XRP2). In Homo sapiens (Human), it is the protein responsible for X-linked forms of retinitis pigmentosa, a disease characterised by severe retinal degeneration.Eukaryotic tubulin-specific chaperone cofactor C (TBCC), a GTPase- activating component of the tubulin-folding supercomplex, which directs the assembly of the alpha- and beta-tubulin heterodimer.The cyclase-associated protein C-CAP/cofactor C-like domain binds G-actin and is responsible for oligomerisation of the entire CAP molecule [], whereas the XRP2 C-CAP/cofactor C-like domain is required for binding of ADP ribosylation factor-like protein 3 (Arl3) [].The central core of the C-CAP/cofactor C-like domain is composed of six coils of right-handed parallel β-helices, termed coils 1-6, which form an elliptical barrel with a tightly packed interior. Each β-helical coil is composed of three relatively short β-strands, designated a-c, separated by sharp turns. Flanking the central β-helical core is an N-terminal β-strand, β0, that packs antiparallel to the core, and strand β7 packs antiparallel to the core near the C-terminal end of the parallel β-helix [, ]. |
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| Protein Domain |
| Type: |
Family |
| Description: |
This entry represents the microtubule-associated protein RP/EB (MAPRE) family, including MAPRE1 (EB1), MAPRE2 (RP1, also known as EB2), MAPRE3 (EBF3, also known as EB3) and their homologues from eukaryotes. Despite their high protein sequence conservation, the individual EBs exhibit different regulatory and functional properties []. For instance, EB1 and EB3, but not EB2, promote persistent microtubule growth by suppressing catastrophes [].EB1 contains an N-terminal calponin homology (CH) domain that is responsible for the interaction with microtubules (MTs), and a C-terminal coiled coil domain that extends into a four-helix bundle, required for dimer formation []. Through their C-terminal sequences, EBs interact with most other known +TIPs (plus end tracking proteins) and recruit many of them to the growing MT ends [, ]. EB1 is involved in MT anchoring at the centrosome and cell migration []. EB2 is highly expressed in pancreatic cancer cells, and seems to be involved in perineural invasion []. EB3 is specifically upregulated upon myogenic differentiation. Knockdown of EB3, but not that of EB1, prevents myoblast elongation and fusion into myotubes []. This entry also includes bZIP transcription factor hapX from the yeast Neosartorya fumigata, which is a transcription factor required for repression of genes during iron starvation []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Scavenger receptors type I and II were the first scavenger receptors purified and are products of alternative splicing of a single gene. They are now named as class A, type I and type II (SR-AI/II) or collectively SR-A member 1. They can recognise a wide variety of ligands, from bacteria and yeast to self (native proteins) and self-modified ligands and they are involved in host defense, homeostasis, antigen presentation, pathogenesis of neurodegenerative disorders and atherosclerosis [, ]. The type I and type II human scavenger receptors are similar to their bovine, rabbit and murine counterparts. They consist of 6 domains: cytoplasmic (I); membrane-spanning (II); spacer (III); α-helical coiled-coil (IV); collagen-like (V); and a type-specific C-terminal (VI) []. Immunohistochemical studies have indicated the presence of scavenger receptors in the macrophages of lipid-rich atherosclerotic lesions, suggesting the involvement of these receptors in atherogenesis [].The macrophage scavenger receptor is trimeric and has unusual ligand-binding properties []. The trimeric structure of the bovine type I scavenger receptor contains 3 extracellular C-terminal cysteine-rich domains connected to the transmembrane domain by a long fibrous stalk. The stalk structure, which consists of an α-helical coiled coil and a collagen-like triple helix, has not previously been observed in an integral membrane protein []. |
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
It is thought that NAPs act as histone chaperones, shuttling both core and linker histones from their site of synthesis in the cytoplasm to the nucleus. The proteins may be involved in regulating gene expression and therefore cellular differentiation [, ].The centrosomal protein c-Nap1, also known as Cep250, has been implicated in the cell-cycle-regulated cohesion of microtubule-organizing centres. This 281kDa protein consists mainly of domains predicted to form coiled coil structures. The C-terminal region defines a novel histone-binding domain that is responsible for targeting CNAP1, and possibly condensin, to mitotic chromosomes []. During interphase, C-Nap1 localizes to the proximal ends of both parental centrioles, but it dissociates from these structures at the onset of mitosis. Re-association with centrioles then occurs in late telophase or at the very beginning of G1 phase, when daughter cells are still connected by post-mitotic bridges. Electron microscopic studies performed on isolated centrosomes suggest that a proteinaceous linker connects parental centrioles and C-Nap1 may be part of a linker structure that assures the cohesion of duplicated centrosomes during interphase, but that is dismantled upon centrosome separation at the onset of mitosis []. The structure of NAP-1 has a long α-helix, responsible for homodimerization via a previously uncharacterized antiparallel non-coiled-coil, and an alpha/beta domain composed of four-stranded antiparallel β-sheet, implicated in protein-protein interaction []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
This family represents ScpA, which along with ScpB () interacts with SMC in vivo forming a complex that is required for chromosome condensation and segregation [, ]. The SMC-Scp complex appears to be similar to the MukB-MukE-Muk-F complex in Escherichia coli [], where MukB () is the homologue of SMC. ScpA and ScpB have little sequence similarity to MukE () or MukF (), they are predicted to be structurally similar, being predominantly α-helical with coiled coil regions. In general scpA and scpB form an operon in most bacterial genomes. Flanking genes are highly variable suggesting that the operon has moved throughout evolution. Bacteria containing an smc gene also contain scpA or scpB but not necessarily both. An exception is found in Deinococcus radiodurans, which contains scpB but neither smc nor scpA. In the archaea the gene order SMC-ScpA is conserved in nearly all species, as is the very short distance between the two genes, indicating co-transcription of the both in different archaeal genera and arguing that interaction of the gene products is not confined to the homologues in Bacillus subtilis. It would seem probable that, in light of all the studies, SMC, ScpA and ScpB proteins or homologues act together in chromosome condensation and segregation in all prokaryotes []. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
The exact function of the Hepatitis C non-structural 5A (NS5A) protein is not known, but it is an active component of the replicase, regulates replication and modulates a range of cellular processes including innate immunity and dysregulated cell growth. NS5A is organised into three domains, labelled I, II and III. Domain I contains a zinc-binding motif and an amphipathic N-terminal helix which promotes membrane association. Mutations disrupting either the membrane anchor or zinc binding are lethal for RNA replication [, ].This entry represents the 1b domain of NS5A. It consists of two distinct anti-parallel β-sheets surrounded by extensive random coil structures []. This domain contains a disulphide bond near its C-terminal not required for the RNA replicase functions of NS5A. The presence of the cited sulphide bond suggests that it is likely responsible of the structural arrangement of domains II and III, thus playing a regulatory role in NS5A function by serving as a conformation switch to modulate functions of NS5A in and out of the replicase []. |
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
The bacteriophage baseplate controls host cell recognition, attachment, tail sheath contraction and viral DNA ejection. The baseplate is a multi-subunit assembly at the distal end of the tail, which is composed of long and short tail fibres []. The tail region is responsible for attachment to the host bacteria during infection: long tail fibres enable host receptor recognition, while irreversible attachment is via short tail fibres. Recognition and attachment induce a conformational transition of the baseplate from a hexagonal to a star-shaped structure. In viruses such as Bacteriophage T4, Gp11 acts as a structural protein to connect the short tail fibres to the baseplate, while Gp9 connects the baseplate with the long tail fibres. Both Gp9 and Gp11 are trimers. Each Gp11 monomer consists of three domains, which are entwined together in the trimer: the N-terminal domains of the three monomers form a central, trimeric, parallel coiled coil surrounded by the entwined middle finger domains; the C-terminal domains appear to be responsible for trimerisation [].This superfamily includes the middle finger domain, which is a seven-stranded, antiparallel, skewed β-roll with one α-helix []. |
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
The bacteriophage baseplate controls host cell recognition, attachment, tail sheath contraction and viral DNA ejection. The baseplate is a multi-subunit assembly at the distal end of the tail, which is composed of long and short tail fibres []. The tail region is responsible for attachment to the host bacteria during infection: long tail fibres enable host receptor recognition, while irreversible attachment is via short tail fibres. Recognition and attachment induce a conformational transition of the baseplate from a hexagonal to a star-shaped structure. In viruses such as Bacteriophage T4, Gp11 acts as a structural protein to connect the short tail fibres to the baseplate, while Gp9 connects the baseplate with the long tail fibres. Both Gp9 and Gp11 are trimers. Each Gp11 monomer consists of three domains, which are entwined together in the trimer: the N-terminal domains of the three monomers form a central, trimeric, parallel coiled coil surrounded by the entwined middle finger domains; the C-terminal domains appear to be responsible for trimerisation [].This superfamily represents the N-terminal domain of Gp11, which has an α-helical structure that assumes an orthogonal bundle topology. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
HR1 was first described as a three times repeated homology region of the N-terminal non-catalytic part of protein kinase PRK1(PKN) []. The first two of these repeats were later shownto bind the small G protein rho [, ]known to activate PKN in its GTP-bound form. Similar rho-binding domains also occur in a number of other protein kinases and in the rho-binding proteins rhophilin and rhotekin. Recently, the structure of the N-terminal HR1 repeat complexed with RhoA has been determined by X-ray crystallography. This domain contains two long alpha helices forming a left-handed antiparallel coiled-coil fold termed the antiparallel coiled- coil (ACC) finger domain. The two long helices encompass the basic region and the leucine repeat region, which are identified as the Rho-binding region [, , ].This entry also includes Transducer of Cdc42-dependent actin assembly protein (TOCA) family proteins which contains a central HR1 (also known as Rho effector motif class 1, REM-1) which is closely related to Cdc42-interacting protein 4 (CIP4), effectors of the Rho family small G protein Cdc2 []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
TIF1-beta, also known as Kruppel-associated Box (KRAB)-associated protein 1 (KAP-1), belongs to the C-VI subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a plant homeodomain (PHD), and a bromodomain (Bromo) positioned C-terminal to the RBCC domain. It acts as a nuclear co-repressor that plays a role in transcription and in the DNA damage response [, , ]. Upon DNA damage, the phosphorylation of KAP-1 on serine 824 by the ataxia telangiectasia-mutated (ATM) kinase enhances cell survival and facilitates chromatin relaxation and heterochromatic DNA repair []. It also regulates CHD3 nucleosome remodelling during the DNA double-strand break (DSB) response []. Meanwhile, KAP-1 can be dephosphorylated by protein phosphatase PP4C in the DNA damage response []. Moreover, KAP-1 is a co-activator of the orphan nuclear receptor NGFI-B (or Nur77) and is involved in NGFI-B-dependent transcription []. It is also a coiled-coil binding partner, substrate and activator of the c-Fes protein tyrosine kinase []. The N-terminal RBCC domains of TIF1-beta are responsible for the interaction with KRAB zinc finger proteins (KRAB-ZFPs), MDM2, MM1, C/EBPbeta, and the regulation of homo- and heterodimerization []. The C-terminal PHD/Bromo domains are involved in interacting with SETDB1, Mi-2alpha and other proteins to form complexes with histone deacetylase or methyltransferase activity [, ]. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
Ferredoxin-NADP(+) oxydoreductase (FNR) () transfers electrons from ferredoxin (or flavodoxin) to NADP(+) to generate NADPH. In eucaryotes, the nuclear-encoded, chloroplast-targeted enzyme contains two domains: an FAD-binding domain (see ) and an NADP(+)-binding domain. With the exception of Gloeobacter violaceus PCC 7421, the predicted sequences of all cyanobacterial petH genes, encoding FNR, correspond to a protein containing three domains. Two domains at the C terminus correspond to the FAD- and NADP(+)-binding domains of higher plants FNR protein, which compose the catalytic domains of the enzyme. The N-terminal domain is similar to phycobilisome (PBS)-associated linker proteins from numerous cyanobacteria [, , ]and is associated with:- CpcD, the phycocyanin (PC)-associated, rod-capping, linker polypeptide of PBS. The similarity spans nearly the entire sequence of this linker class.- CpcC, the PC-associated rod linker polypeptide. The similarity is confined only to the C terminus of this linker class.- ApcC, the allophycocyanin (APC)-associated, core linker polypeptide. The similarity only correspond to about half of the molecule.The CpcD-like domain has an elongated shape and consists of a three-strandedβ-sheet, two α-helices, one of which has only about one turn, and theconnecting random coil segments []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
(Bovine immunodeficiency virus) (BIV), like the human immunodeficiency virus, is a lentivirus. It shows a great deal of genomic diversity, mostly in the viral envelope gene []. This property of the BIV group of viruses may play an important role in the pathobiology of the virus, particularly the conserved (C) 2, hypervariable (V) 1, V2 and C3 regions [].The surface protein (SU) attaches the virus to the host cell by binding to its receptor. This interaction triggers the refolding of the transmembrane protein (TM) and is thought to activate its fusogenic potential by unmasking its fusion peptide. Fusion occurs at the host cell plasma membrane.The transmembrane protein (TM) acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm. |
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| Protein Domain |
| Type: |
Family |
| Description: |
RPGR-interacting protein 1 (RPGRIP1) is mutated in the eye disease Leber congenital amaurosis (LCA) and its structural homologue, RPGRIP1-like (RPGRIP1L, also called NPHP8 or fantom), is mutated in many different ciliopathies [, ]. Both are multidomain proteins that are predicted to interact with retinitis pigmentosa G-protein regulator (RPGR) []. Both consist of an N-terminal coiled coil domain, two C2 domains (C2N and C2C), and a C-terminal RPGR-interacting domain (RID). RID is a C2 domain with a canonical beta sandwich structure that does not bind Ca2+ and/or phospholipids and thus constitutes a unique type of protein-protein interaction module [].Both RPGRIP1 and RPGRIP1L interact with the ciliary transition zone protein nephrocystin 4 (NPHP4) via their C2C domain [, ]. An hypothesis is that RPGRIP1 and RPGRIP1L function as cilium-specific scaffolds that recruit a Nek4 signaling network which regulates cilium stability []. The expression of RPGRIP1 seems to be limited to photoreceptors and amacrine cells in the retina [], whereas RPGRIP1L is found in other tissues as well. |
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| Protein Domain |
| Type: |
Homologous_superfamily |
| Description: |
The bacteriophage baseplate controls host cell recognition, attachment, tail sheath contraction and viral DNA ejection. The baseplate is a multi-subunit assembly at the distal end of the tail, which is composed of long and short tail fibres []. The tail region is responsible for attachment to the host bacteria during infection: long tail fibres enable host receptor recognition, while irreversible attachment is via short tail fibres. Recognition and attachment induce a conformational transition of the baseplate from a hexagonal to a star-shaped structure. In viruses such as Bacteriophage T4, Gp11 acts as a structural protein to connect the short tail fibres to the baseplate, while Gp9 connects the baseplate with the long tail fibres. Both Gp9 and Gp11 are trimers. Each Gp11 monomer consists of three domains, which are entwined together in the trimer: the N-terminal domains of the three monomers form a central, trimeric, parallel coiled coil surrounded by the entwined middle finger domains; the C-terminal domains appear to be responsible for trimerisation [].This superfamily represents the C-terminal domain of Gp11. |
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| Publication |
| First Author: |
Mascarenhas J |
| Year: |
2002 |
| Journal: |
EMBO J |
| Title: |
Cell cycle-dependent localization of two novel prokaryotic chromosome segregation and condensation proteins in Bacillus subtilis that interact with SMC protein. |
| Volume: |
21 |
| Issue: |
12 |
| Pages: |
3108-18 |
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•
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| Publication |
| First Author: |
Yamazoe M |
| Year: |
1999 |
| Journal: |
EMBO J |
| Title: |
Complex formation of MukB, MukE and MukF proteins involved in chromosome partitioning in Escherichia coli. |
| Volume: |
18 |
| Issue: |
21 |
| Pages: |
5873-84 |
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•
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| Publication |
| First Author: |
Cook MC |
| Year: |
2006 |
| Journal: |
Curr Opin Immunol |
| Title: |
ENU-mutagenesis: insight into immune function and pathology. |
| Volume: |
18 |
| Issue: |
5 |
| Pages: |
627-33 |
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•
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| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
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•
•
•
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| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein Coding Gene |
| Type: |
protein_coding_gene |
| Organism: |
mouse, laboratory |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
414
 |
| Fragment?: |
false |
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•
•
•
•
•
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| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
253
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
810
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
224
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
217
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
430
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
443
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
457
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
410
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
335
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
802
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Rambaud J |
| Year: |
2009 |
| Journal: |
J Biol Chem |
| Title: |
TIF1beta/KAP-1 is a coactivator of the orphan nuclear receptor NGFI-B/Nur77. |
| Volume: |
284 |
| Issue: |
21 |
| Pages: |
14147-56 |
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•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
639
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
375
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
224
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
132
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
483
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
137
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
335
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
401
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
321
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
194
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
731
|
| Fragment?: |
true |
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•
•
•
•
•
|
