| Predicate | Object |
|---|---|
| rdf:type | |
| biopax3:comment |
FUNCTION: E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation (By similarity). Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c- Myb-mediated transactivation, in B-lymphocytes. Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor. Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Homotrimer (By similarity). Homooligomer (By similarity). N-terminal region is dimeric while C-terminal region is trimeric; maybe providing a mode of oligomerization. Binds to TNFRSF5/CD40 and TNFRSF11A/RANK (By similarity). Associates with NGFR, TNFRSF17, IRAK1, IRAK2, IRAK3, IRAK4, PELI1, PELI2, PELI3, RIPK2, MAP3K1, MAP3K5, MAP3K14, CSK, TRAF, TRAF-interacting protein TRIP and TNF receptor associated protein TDP2. Binds UBE2V1. Interacts with MAVS/IPS1. Interacts with TAX1BP1 (By similarity). Interacts with IL17R. Interacts with SQSTM1 bridging NTRK1 and NGFR. Forms a ternary complex with SQSTM1 and PRKCZ. Interacts with IL1RL1. Interacts with AJUBA (By similarity). Interacts with TRAFD1. Interacts with TICAM1 and TICAM2. Interacts with ZFAND5. Interacts with ARRB1 and ARRB2 (By similarity). Interacts with MAP3K7 and TAB1/MAP3K7IP1; during IL-1 signaling. Interacts with UBE2N. Interacts with TGFBR1, HDAC1 and RANGAP1. Interacts with AKT1, AKT2 and AKT3. Interacts (via TRAF domains) with NUMBL (via C- terminal) (By similarity). Interacts (via TRAF domains) with WDR34 (via WD domains). Interacts with RBCK1 (By similarity). Interacts with TRAF3IP2 (By similarity). Interacts with LIMD1 (via LIM domains). SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cytoplasm, cell cortex (By similarity). Nucleus (By similarity). ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=P70196-1; Sequence=Displayed; Name=2; IsoId=P70196-2; Sequence=VSP_007404, VSP_007405; Note=No experimental confirmation available; TISSUE SPECIFICITY: Highly expressed in brain, lung, liver, skeletal muscle, and kidney; lower expression in heart, spleen, and testis. DOMAIN: The coiled coil domain mediates homo- and hetero- oligomerization. DOMAIN: The MATH/TRAF domain binds to receptor cytoplasmic domains. PTM: Sumoylated on Lys-124, Lys-142 and Lys-461 by SUMO1 (By similarity). PTM: Polyubiquitinated; after cell stimulation with IL-1-beta or TGF-beta. This ligand-induced cell stimulation leads to dimerization/oligomerization of TRAF6 molecules, followed by auto- ubiquitination which involves UBE2N and UBE2V1 and leads to TRAF6 activation. This 'Lys-63' site-specific poly-ubiquitination appears to be associated with the activation of signaling molecules. Endogenous autoubiquitination occurs only for the cytoplasmic form (By similarity). DISRUPTION PHENOTYPE: Abrogation of IL-1-induced activation of NF- kappa-B, MAPK8/JNK and MAPK14/p38. Animals appears normal at birth but becomes smaller after one week. Show runting, failure of tooth eruption and die after three weeks. Exhibit severe osteopetrosis, thymic atrophy, lymph node deficiency, splenomegaly, and have alopecia and lack sweat glands. SIMILARITY: Belongs to the TNF receptor-associated factor family. A subfamily. SIMILARITY: Contains 1 MATH domain. SIMILARITY: Contains 1 RING-type zinc finger. SIMILARITY: Contains 2 TRAF-type zinc fingers. GENE SYNONYMS:Traf6. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.,
SEQUENCE 530 AA; 60070 MW; F8389250425E4E2D CRC64;
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| biopax3:xref | |
| biopax3:displayName |
TRAF6_MOUSE
|
| biopax3:name |
6.3.2.-,
E3 ubiquitin-protein ligase TRAF6,
Traf6
|
| biopax3:organism | |
| biopax3:sequence |
MSLLNCENSCGSSQSSSDCCAAMAASCSAAVKDDSVSGSASTGNLSSSFMEEIQGYDVEFDPPLESKYECPICLMALREAVQTPCGHRFCKACIIKSIRDAGHKCPVDNEILLENQLFPDNFAKREILSLTVKCPNKGCLQKMELRHLEDHQVHCEFALVNCPQCQRPFQKCQVNTHIIEDCPRRQVSCVNCAVSMAYEEKEIHDQSCPLANIICEYCGTILIREQMPNHYDLDCPTAPIPCTFSVFGCHEKMQRNHLARHLQENTQLHMRLLAQAVHNVNLALRPCDAASPSRGCRPEDPNYEETIKQLESRLVRQDHQIRELTAKMETQSMYVGELKRTIRTLEDKVAEMEAQQCNGIYIWKIGNFGMHLKSQEEERPVVIHSPGFYTGRPGYKLCMRLHLQLPTAQRCANYISLFVHTMQGEYDSHLPWPFQGTIRLTILDQSEALIRQNHEEVMDAKPELLAFQRPTIPRNPKGFGYVTFMHLEALRQGTFIKDDTLLVRCEVSTRFDMGGLRKEGFQPRSTDAGV
|
| biopax3:standardName |
TNF receptor-associated factor 6
|