|  Help  |  About  |  Contact Us

Search our database by keyword

- or -

Examples

  • Search this entire website. Enter identifiers, names or keywords for genes, diseases, strains, ontology terms, etc. (e.g. Pax6, Parkinson, ataxia)
  • Use OR to search for either of two terms (e.g. OR mus) or quotation marks to search for phrases (e.g. "dna binding").
  • Boolean search syntax is supported: e.g. Balb* for partial matches or mus AND NOT embryo to exclude a term

Search results 1 to 19 out of 19 for Traf6

Category restricted to ProteinDomain (x)

0.018s

Categories

Category: ProteinDomain
Type Details Score
Protein Domain
Type: Family
Description: TNF receptor-associated factor 6 (TRAF6) regulates a diverse array of processes, including adaptive immunity, innate immunity, bone metabolism and tissue development. It is a unique member of the TRAF family of adaptor proteins in that it is involved in both the TNF receptor superfamily and the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily signal transduction pathways [, , , ]. TRAF6 possesses ubiquitin ligase activity that controls the activation of IKK and NF-kappaB [, ]. TRAF6 contains a RING finger domain, five zinc finger domains, and a TRAF domain.
Protein Domain
Type: Domain
Description: This domain is the second of three zinc fingers of Homo sapiens TNF receptor associated factor 6 (TRAF6). TRAF6 mediates Lys63 (K63)-linked polyubiquitination for Necrosis Factor-kappaB activation. The first three residues and the last Cys of finger 1 form a classical type I β-turn [].
Protein Domain
Type: Family
Description: TANK-binding kinase 1 (TBK1) and inducible IkappaB-kinase (IKK) are central regulators of type-I interferon induction. TANK (TRAF family member-associated NF-kappa-B activator) is aadaptor protein that connects IKK complexes with IKK epsilon and TBK1 kinases [, ]. It negatively regulates NF-kappaB activation by DNA damage via inhibiting ubiquitination of TRAF6 []. It is also a negative regulator of osteoclastogenesis and bone formation [].
Protein Domain
Type: Domain
Description: TNF receptor-associated factor 6 (TRAF6) regulates a diverse array of processes, including adaptive immunity, innate immunity, bone metabolism and tissue development. It is a unique member of the TRAF family of adaptor proteins in that it is involved in both the TNF receptor superfamily and the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) superfamily signal transduction pathways [, , , ]. TRAF6 possesses ubiquitin ligase activity that controls the activation of IKK and NF-kappaB [, ]. TRAF6 contains a RING finger domain, five zinc finger domains, and a TRAF domain.The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded β-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors [, ].
Protein Domain
Type: Domain
Description: TAB2 (TGF-beta-activated kinase 1 and MAP3K7-binding protein 2) is an adaptor protein that regulates activation of TAK1, a MAP kinase kinase kinase (MAPKKK), through linking TAK1 to TRAF6 in the Interleukin-1 (IL-1) induced NF-kappaB activation pathway []. TAB3 is a TAB2-like TAK1-binding protein that activates NF-kappaB similar to TAB2 []. It activates TAK1 and regulates its association with TRAF2 and TRAF6. Moreover, TAB3 interacts with TRAF6 and TRAF2 in an IL-1- and a TNF-dependent manner, respectively. TAB2 and TAB3 function redundantly as mediators of TAK1 activation in IL-1 and TNF signal transduction []. Both of them contain an N-terminal CUE domain, a coiled-coil (CC) region, a TAK1-binding domain and a C-terminal Npl4 zinc finger (NZF) ubiquitin-binding domain (UBD) [].This entry represents the CUE domain found in TAB2 and TAB3.
Protein Domain
Type: Domain
Description: This is an immunoglobulin-like domain which can be found in the mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) paracaspase. Malt1 is a key component of the Carma1/Bcl10/MALT1 signalosome and is critical for NF-kB signaling in multiple contexts. The MALT1 C-terminal Ig domain is suggested to recruit key factors to promote NF-kB activation. It is also proposed to undergo Lys63-linked ubiquitylation via TRAF6 in potentially nine different lysines to recruit the IKK complex [, , ].
Protein Domain
Type: Family
Description: This family represents Protein K7 from Orthopoxvirus. K7 is Bcl-2-like protein which, through its interaction with the DEAD box RNA helicase DDX3X/DDX3, prevents TBK1/IKKepsilon-mediated IRF3 activation []. It contributes to virulence by binding to the host TRAF6 and IRAK2 and preventing host NF-kappa-B activation and affects the acute immune response to infection [, , ]. In vaccinia virus, this protein has been related to the increase in cellular histone methylation during infection [].
Protein Domain
Type: Family
Description: TRAF-interacting protein with a forkhead-associated domain (TIFA), also called T2BP, is an adapter protein which mediates the IRAK1 and TRAF6 interaction following IL-1 stimulation, resulting in the downstream activation of NF-kappa-B and c-Jun amino-terminal kinase (JNK) []. TIFA has been shown to induce the oligomerization and polyubiquitination of TRAF6, which in turn activates transforming growth factor-activated kinase (TAK1) and IkappaB kinase (IKK) []. TIFA contains a phosphothreonine and phosphoserine-binding FHA domain []and a consensus TRAF6-binding motif [].
Protein Domain
Type: Family
Description: PP4R1 is a regulatory subunit of serine/threonine-protein phosphatase 4 (PP4). The catalytic subunit of PP4 (PP4C) belongs to the PP2A family of serine/threonine protein phosphatases []. Although 65% identical to the catalytic subunit of PP2AC, PP4C does not associate with the regulatory subunit of PP2A. Instead, PP4C associates with two other regulatory subunits, PP4R1 []and PP4R2 [].PP4R1 targets TRAF2 and TRAF6 to mediate inhibition of NF-kB activation [].
Protein Domain
Type: Family
Description: Microtubule-associated serine/threonine-protein kinase 2 (MAST2, also known as MAST205) belongs to the MAST family, which is characterised by containing a serine/threonine kinase domain and a PDZ (postsynaptic density protein-95/discs large/zona occludens-1) domain []. MAST2 regulates lipopolysaccharide-induced IL-12 synthesis in macrophages by forming a complex with TRAF6, resulting in the inhibition of TRAF6 NF-kappa-B activation [, ]. It localises in the DAPC/UAPC, which is found within the postsynaptic region of the neuromuscular junction (NMJ) and central synapses []. It also functions in spermatid maturation in mammals [].
Protein Domain
Type: Family
Description: TNF receptor-associated factor 4 (TRAF4) is an adapter protein and signal transducer that links members of the tumor necrosis factor receptor (TNFR) family to different signaling pathways. TRAF4 plays a role in the activation of NF-kappa-B and JNK, and in the regulation of cell survival and apoptosis. It regulates activation of NF-kappa-B in response to signaling through Toll-like receptors. TRAF4 modulates TRAF6 functions [, , , , , ]. In mouse, it has been shown to be required for normal skeleton development, and for normal development of the respiratory tract []. TRAF4 contains a RING finger domain, seven zinc finger domains, and a TRAF domain.
Protein Domain
Type: Domain
Description: TNF receptor-associated factor 4 (TRAF4) is an adapter protein and signal transducer that links members of the tumor necrosis factor receptor (TNFR) family to different signaling pathways. TRAF4 plays a role in the activation of NF-kappa-B and JNK, and in the regulation of cell survival and apoptosis. It regulates activation of NF-kappa-B in response to signaling through Toll-like receptors. TRAF4 modulates TRAF6 functions [, , , , , ]. In mouse, it has been shown to be required for normal skeleton development, and for normal development of the respiratory tract []. TRAF4 contains a RING finger domain, seven zinc finger domains, and a TRAF domain.The TRAF domain can be divided into a more divergent N-terminal alpha helical region (TRAF-N), and a highly conserved C-terminal MATH subdomain (TRAF-C) with an eight-stranded β-sandwich structure. TRAF-N mediates trimerization while TRAF-C interacts with receptors [, ].
Protein Domain
Type: Family
Description: The tumour necrosis factor (TNF) receptor associated factors (TRAFs) are major signal transducers for the TNF receptor (TNFR) superfamily and the interleukin-1 receptor/Toll-like receptor superfamily in mammals []. TRAFs constitute a family of genetically conserved adapter proteins found in mammals (TRAF1-6) as well as in other multicellular organisms such as Drosophila [], Caenorhabditis elegans []. TRAF2 is the prototypical member of the family. Mammalian TRAF1 and TRAF2 were the first members initially identified by their association with TNFR2. The TRAF1/TRAF2 and TRAF3/TRAF5 gene pairs may have arisen from recent independent gene duplications and to share a common ancestral gene. TRAF4 and TRAF6 precursor genes may have arisen earlier during evolution, with the divergence of the TRAF6 precursor occurring earliest of all. Except TRAF1, this PIRSF has a general domain architecture containing one N-terminal RING finger, a variable number of middle region of TRAF-type zinc finger and C2H2 type of zinc finger, and one C-terminal MATH domain. TRAF1 is unique in the family in that it lacks the N-terminal RING and zinc-finger domains []. This has rendered TRAF1 unable to promote TNF receptor signalling and act as a "dominant negative"TRAF []. Also TRAF1 is a substrate for caspases activated by TNF family death receptors []. The larger C-terminal cleaved fragment can bind to and sequester TRAF2 from TNFR1 complex, therefore modulating TNF induced NFkB activation []. A wide range of biological functions, such as adaptive and innate immunity, embryonic development, stress response and bone metabolism, are mediated by TRAFs through the induction of cell survival, proliferation, differentiation and death. TRAFs are functionally divergent from a perspective of both upstream and downstream TRAF signal transduction pathways and of signalling-dependent regulation of TRAF trafficking. Each TRAF protein interacts with and mediates the signal transduction of multiple receptors, and in turn each receptor utilises multiple TRAFs for specific functions []. About 40 interaction partners of TRAF have been described thus far, including receptors, kinases, regulators and adaptor proteins.TRAF proteins can be recruited to and activated by ligand-engaged receptors in least three distinct ways []. 1) Members of the TNFR superfamily that do not contain intracellular death domains, such as TNFR2 and CD40, recruit TRAFs directly via short sequences in their intracellular tails []. 2) Those that contain an intracellular death domain, such as TNFR1, first recruit an adapter protein, TRADD, via a death-domain-death-domain interaction, which then serves as a central platform of the TNFR1 signalling complex, which assembles TRAF2 and RIP for survival signalling, and FADD and caspase-8 for the induction of apoptosis. 3) Members of the IL-1R/TLR superfamily contain a protein interaction module known as the TIR domain, which recruits, sequentially, MyD88, a TIR domain and death domain containing protein, and IRAKs, adapter Ser/Thr kinases with death domains. IRAKs in turn associate with TRAF6 to elicit signalling by IL-1 and pathogenic components such as LPS. A common mechanism for the membrane-proximal event in TRAF signalling has been revealed by the conserved trimeric association in the crystal structure of the TRAF domain of TRAF2 [].This entry represents the TNF receptor associated factors found in metazoa.
Protein Domain
Type: Family
Description: The tumour necrosis factor (TNF) receptor associated factors (TRAFs) are major signal transducers for the TNF receptor (TNFR) superfamily and the interleukin-1 receptor/Toll-like receptor superfamily in mammals []. TRAFs constitute a family of genetically conserved adapter proteinsfound in mammals (TRAF1-6) as well as in other multicellular organisms such as Drosophila [], Caenorhabditis elegans []. TRAF2 is the prototypical member of the family. Mammalian TRAF1 and TRAF2 were the first members initially identified by their association with TNFR2. The TRAF1/TRAF2 and TRAF3/TRAF5 gene pairs may have arisen from recent independent gene duplications and to share a common ancestral gene. TRAF4 and TRAF6 precursor genes may have arisen earlier during evolution, with the divergence of the TRAF6 precursor occurring earliest of all. Except TRAF1, this PIRSF has a general domain architecture containing one N-terminal RING finger, a variable number of middle region of TRAF-type zinc finger and C2H2 type of zinc finger, and one C-terminal MATH domain. TRAF1 is unique in the family in that it lacks the N-terminal RING and zinc-finger domains []. This has rendered TRAF1 unable to promote TNF receptor signalling and act as a "dominant negative"TRAF []. Also TRAF1 is a substrate for caspases activated by TNF family death receptors []. The larger C-terminal cleaved fragment can bind to and sequester TRAF2 from TNFR1 complex, therefore modulating TNF induced NFkB activation []. A wide range of biological functions, such as adaptive and innate immunity, embryonic development, stress response and bone metabolism, are mediated by TRAFs through the induction of cell survival, proliferation, differentiation and death. TRAFs are functionally divergent from a perspective of both upstream and downstream TRAF signal transduction pathways and of signalling-dependent regulation of TRAF trafficking. Each TRAF protein interacts with and mediates the signal transduction of multiple receptors, and in turn each receptor utilises multiple TRAFs for specific functions []. About 40 interaction partners of TRAF have been described thus far, including receptors, kinases, regulators and adaptor proteins.TRAF proteins can be recruited to and activated by ligand-engaged receptors in least three distinct ways []. 1) Members of the TNFR superfamily that do not contain intracellular death domains, such as TNFR2 and CD40, recruit TRAFs directly via short sequences in their intracellular tails []. 2) Those that contain an intracellular death domain, such as TNFR1, first recruit an adapter protein, TRADD, via a death-domain-death-domain interaction, which then serves as a central platform of the TNFR1 signalling complex, which assembles TRAF2 and RIP for survival signalling, and FADD and caspase-8 for the induction of apoptosis. 3) Members of the IL-1R/TLR superfamily contain a protein interaction module known as the TIR domain, which recruits, sequentially, MyD88, a TIR domain and death domain containing protein, and IRAKs, adapter Ser/Thr kinases with death domains. IRAKs in turn associate with TRAF6 to elicit signalling by IL-1 and pathogenic components such as LPS. A common mechanism for the membrane-proximal event in TRAF signalling has been revealed by the conserved trimeric association in the crystal structure of the TRAF domain of TRAF2 [].
Protein Domain
Type: Domain
Description: This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C terminus of TRIM38, which is also known as RING finger protein 15 (RNF15) or RORET. TRIM proteins are defined by the presence of the tripartite motif RING/B-box/coiled-coil region and are also known as RBCC proteins []. TRIM38 has been shown to act as a suppressor in TOLL-like receptor (TLR)-mediated interferon (IFN)-beta induction by promoting degradation of TRAF6 and NAP1 through the ubiquitin-proteasome system [, ]. Another study has shown that TRIM38 may act as a novel negative regulator for TLR3-mediated IFN-beta signaling by targeting TRIF for degradation []. TRIM38 has been identified as a critical negative regulator in TNFalpha- and IL-1beta-triggered activation of NF-kappaB and MAP Kinases (MAPKs); it causes degradation of two essential cellular components, TGFbeta-associated kinase 1 (TAK1)-associating chaperones 2 and 3 (TAB2/3) []. The degradation is promoted through a lysosomal-dependent pathway, which requires the C-terminal PRY-SPRY of TRIM38. Enterovirus 71 infection induces degradation of TRIM38, suggesting that TRIM38 may play a role in viral infections [].
Protein Domain
Type: Domain
Description: This entry represents a domain named CUPID (Cytohesin Ubiquitin Protein Inducing Domain) that is found in animal proteins. It is found towards the N-terminal end of Innate immunity activator protein (INAVA, Innate Immune Activator), a risk factor for the chronic inflammatory bowel diseases (IBD). Mice lacking the protein show defects in intestinal barrier integrity at steady state and greater susceptibility to mucosal infection. CUPID is also found towards the N-terminal end of Coiled-coil domain-containing protein 120 (CC120) and C-terminal to the FERM domain in FERM domain-containing protein 4A/B (FRM4A/B), which are implicated in neurite outgrowth, and in human cancer, Alzheimer's, celiac, and heart disease. All appear to bind the ARF-GEF (guanine nucleotide-exchange factors) cytohesin family members, such as proteins (ARF 1-4), which regulate cell membrane and F-actin dynamics. INAVA-CUPID binds cytohesin 2 (also known as ARNO), targets the molecule to lateral membranes of epithelial monolayers, and enables ARNO to affect F-actin assembly that underlies cell-cell junctions and barrier function. In the case of inflammatory signalling, ARNO can coordinate CUPID function by binding and inhibiting CUPID activity of acting as an enhancer of TRAF6 dependent polyubiquitination. In other words, ARNO acts as a negative-regulator of inflammatory responses. In summary, INAVA-CUPID exhibits dual functions, coordinated directly by ARNO, that bridge epithelial barrier function with extracellular signals and inflammation [, , ].
Protein Domain
Type: Domain
Description: This entry represents the N-terminal domain of family members such as the Matrix (Mx) and Matrix protein long (ML) proteins. They are found in Thogoto virus (THOV), a tick-transmitted orthomyxovirus with a genome consisting of six single-stranded RNA segments that encode seven structural proteins []. Matrix proteins of the family Orthomyxoviridae are major structural components of the viral capsid, located below the viral lipid membrane and provide protection for viral ribonucleoproteins (vRNPs) []. They serve as a major participant during the processes of virus invasion and budding. Furthermore, they play specific roles throughout the viral life cycle, usually by interacting with other viral components or host cellular proteins [].ML protein, an extended version of the viral M protein, is a viral IFN antagonist. ML is essential for virus growth and pathogenesis in an IFN-competent host. In the presence of ML the activation and/or action of the interferon regulatory factor-3 (IRF-3) is severely affected. This effect depends on direct interaction of ML with the transcription factor IIB (TFIIB). ML suppresses IRF-7 in a similar manner as it suppresses IRF-3. Studies have revealed that ML associates with IRF-7 and prevents IRF-7 dimerization and interaction with TRAF6 [].Structural analysis revealed that N-terminal fragment of M protein (MN) undergoes conformational changes that result in specific, pH-dependent inter-molecular interactions. Comparison of THOV MN and influenza A virus (IAV) MN region, showed low sequence identity. However, superimposition of the two structures in neutral condition showed that both matrix proteins contain nine helices connected with same topology. Since the matrix layer of IAV disassembles in acidic endosome at the beginning of infection and repacks in the neutral cytoplasm, a change of pH might be a key regulator for the capsid assembly/disassembly transition during these processes. Hence, pH-dependent conformational transition model was studied in THOV MN, where interactions such as hydrogen bonds and hydrophobic interactions are suggested to be involved in THOV matrix assembly [].
Protein Domain
Type: Domain
Description: Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [, , , , ]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. This entry represents the AN1-type zinc finger domain, which has a dimetal (zinc)-bound alpha/beta fold. This domain was first identified as a zinc finger at the C terminus of AN1 , a ubiquitin-likeprotein in Xenopus laevis []. The AN1-type zinc finger contains six conserved cysteines and two histidines that could potentially coordinate 2 zinc atoms.Certain stress-associated proteins (SAP) contain AN1 domain, often in combination with A20 zinc finger domains (SAP8) or C2H2 domains (SAP16) []. For example, the human protein Znf216 has an A20 zinc-finger at the N terminus and an AN1 zinc-finger at the C terminus, acting to negatively regulate the NFkappaB activation pathway and to interact with components of the immune response like RIP, IKKgamma and TRAF6. The interact of Znf216 with IKK-gamma and RIP is mediated by the A20 zinc-finger domain, while its interaction with TRAF6 is mediated by the AN1 zinc-finger domain; therefore, both zinc-finger domains are involved in regulating the immune response []. The AN1 zinc finger domain is also found in proteins containing a ubiquitin-like domain, which are involved in the ubiquitination pathway []. Proteins containing an AN1-type zinc finger include:Ascidian posterior end mark 6 (pem-6) protein [].Human AWP1 protein (associated with PRK1), which is expressed during early embryogenesis [].Human immunoglobulin mu binding protein 2 (SMUBP-2), mutations in which cause muscular atrophy with respiratory distress type 1 [].
Protein Domain
Type: Homologous_superfamily
Description: Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [, , , , ]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few []. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target. This entry represents the AN1-type zinc finger domain, which has a dimetal (zinc)-bound alpha/beta fold. This domain was first identified as a zinc finger at the C terminus of AN1 , a ubiquitin-likeprotein in Xenopus laevis []. The AN1-type zinc finger contains six conserved cysteines and two histidines that could potentially coordinate 2 zinc atoms.Certain stress-associated proteins (SAP) contain AN1 domain, often in combination with A20 zinc finger domains (SAP8) or C2H2 domains (SAP16) []. For example, the human protein Znf216 has an A20 zinc-finger at the N terminus and an AN1 zinc-finger at the C terminus, acting to negatively regulate the NFkappaB activation pathway and to interact with components of the immune response like RIP, IKKgamma and TRAF6. The interact of Znf216 with IKK-gamma and RIP is mediated by the A20 zinc-finger domain, while its interaction with TRAF6 is mediated by the AN1 zinc-finger domain; therefore, both zinc-finger domains are involved in regulating the immune response []. The AN1 zinc finger domain is also found in proteins containing a ubiquitin-like domain, which are involved in the ubiquitination pathway []. Proteins containing an AN1-type zinc finger include:Ascidian posterior end mark 6 (pem-6) protein [].Human AWP1 protein (associated with PRK1), which is expressed during early embryogenesis [].Human immunoglobulin mu binding protein 2 (SMUBP-2), mutations in which cause muscular atrophy with respiratory distress type 1 [].