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Details on Person UniProt:Q13114 TRAF3
| Class:Id | ReferenceGeneProduct:66373 |
|---|---|
| _chainChangeLog | chain:1-568 added on Fri February 6 2015 |
| _displayName | UniProt:Q13114 TRAF3 |
| _timestamp | 2025-08-15 22:12:39 |
| chain | chain:1-568 |
| checksum | 9456E440C0A90FBF |
| comment | FUNCTION Cytoplasmic E3 ubiquitin ligase that regulates various signaling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in both immune and non-immune cell types (PubMed:33148796, PubMed:33608556). In TLR and RLR signaling pathways, acts as an E3 ubiquitin ligase promoting the synthesis of 'Lys-63'-linked polyubiquitin chains on several substrates such as ASC that lead to the activation of the type I interferon response or the inflammasome (PubMed:25847972, PubMed:27980081). Following the activation of certain TLRs such as TLR4, acts as a negative NF-kappa-B regulator, possibly to avoid unregulated inflammatory response, and its degradation via 'Lys-48'-linked polyubiquitination is required for MAPK activation and production of inflammatory cytokines. Alternatively, when TLR4 orchestrates bacterial expulsion, TRAF3 undergoes 'Lys-33'-linked polyubiquitination and subsequently binds to RALGDS, mobilizing the exocyst complex to rapidly expel intracellular bacteria back for clearance (PubMed:27438768). Also acts as a constitutive negative regulator of the alternative NF-kappa-B pathway, which controls B-cell survival and lymphoid organ development. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14.CATALYTIC ACTIVITY S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.SUBUNIT Homotrimer. Heterotrimer with TRAF2 and TRAF5. Interacts with LTBR/TNFRSF3, TNFRSF4, TNFRSF5/CD40, TNFRSF8/CD30, TNFRSF13C TNFRSF17/BCMA, TLR4 and EDAR. Interacts with MAP3K5, MAP3K14, TRAIP/TRIP, TDP2/TTRAP, TANK/ITRAF and TRAF3IP1. Interaction with TNFRSF5/CD40 is modulated by TANK/ITRAF, which competes for the same binding site. Interacts with TICAM1. Interacts with TRAFD1. Interacts with OTUB1, OTUB2 and OTUD5. Interacts with RNF216, OPTN and TBK1. Identified in a complex with TRAF2, MAP3K14 and BIRC3. Interacts with BIRC2 and BIRC3. Upon exposure to bacterial lipopolysaccharide (LPS), recruited to a transient complex containing TLR4, TRAF3, TRAF6, IKBKG, MAP3K7, MYD88, TICAM1, BIRC2, BIRC3 and UBE2N (By similarity). Interacts (via RING-type zinc finger domain) with SRC. Interacts with CARD14. Interacts (via MATH domain) with PTPN22; the interaction promotes TRAF3 polyubiquitination (PubMed:23871208). Interacts with MAVS (PubMed:19893624, PubMed:27980081). Directly interacts with DDX3X; this interaction stimulates TRAF3 'Lys-63' ubiquitination (PubMed:27980081). Interacts with IRF3 (PubMed:27980081). Interacts with IKBKE in the course of Sendai virus infection (PubMed:27980081). Interacts with TRIM35 (PubMed:32562145). Interacts with GAPDH; promoting TRAF3 ubiquitination (PubMed:27387501). Interacts with PPP3CA and PPP3CB (By similarity). Interacts with ATP1B1; promoting TRAF3 ubiquitination (PubMed:27387501). Interacts with RALGDS (PubMed:27438768). Interacts with FBXO11 (PubMed:36897010).SUBUNIT (Microbial infection) Interacts (via N-terminus) with New York hantavirus glycoprotein N (via C-terminus); this interaction inhibits the formation of TRAF3-TBK1 complexes.SUBUNIT (Microbial infection) Interacts with Andes hantavirus glycoprotein N (via C-terminus); this interaction inhibits the formation of TRAF3-TBK1 complexes.SUBUNIT (Microbial infection) Interacts with Tula hantavirus glycoprotein N (via C-terminus); this interaction inhibits the formation of TRAF3-TBK1 complexes.SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus protein LMP1.INTERACTION Undergoes endocytosis together with TLR4 upon LPS signaling (By similarity). Co-localized to mitochondria with TRIM35 (PubMed:32562145).ALTERNATIVE PRODUCTS The MATH/TRAF domain binds to receptor cytoplasmic domains.DOMAIN The Ring-type zinc finger domain is required for its function in down-regulation of NFKB2 proteolytic processing.PTM Undergoes 'Lys-48'-linked polyubiquitination, leading to its proteasomal degradation in response to signaling by TNFSF13B, TLR4 or through CD40. 'Lys-48'-linked polyubiquitinated form is deubiquitinated by OTUD7B, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B. Undergoes 'Lys-63'-linked ubiquitination during early stages of virus infection, and 'Lys-48'-linked ubiquitination during later stages. Undergoes both 'Lys-48'-linked and 'Lys-63'-linked ubiquitination in response to TLR3 and TLR4 signaling. 'Lys-63'-linked ubiquitination can be mediated by TRIM35. Deubiquitinated by OTUB1, OTUB2 and OTUD5. Undergoes 'Lys-63'-linked deubiquitination by MYSM1 to terminate the pattern-recognition receptors/PRRs pathways (By similarity). Also undergoes 'Lys-29'-linked ubiquitination on Cys-56 and Cys-124 by NEDD4L; leading to increased 'Lys-48'- and 'Lys-63'-linked ubiquitination as well as increased binding to TBK1 (PubMed:33608556). TLR4 signals emanating from bacteria containing vesicles trigger 'Lys-33'-linked polyubiquitination that promotes the assembly of the exocyst complex thereby connecting innate immune signaling to the cellular trafficking apparatus (PubMed:27438768). Deubiquitinated by USP25 during viral infection, leading to TRAF3 stabilization and type I interferon production (By similarity). Ubiquitinated at Lys-329 by the SCF(FBXL2) complex, leading to its degradation by the proteasome (By similarity). 'Lys-63'-linked ubiquitination by FBXO11 in a NEDD8-dependent manner promotes the amplification of IFN-I signaling (PubMed:36897010).PTM (Microbial infection) Cleaved by enterovirus D68 protease 2A; leading to inhibition of NF-kappa-B or IFN-beta triggered by TRAF3.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the TNF receptor-associated factor family. A subfamily. |
| description | recommendedName: fullName evidence="65"TNF receptor-associated factor 3 ecNumber evidence="34"2.3.2.27 alternativeName: fullName evidence="62"CD40 receptor-associated factor 1 shortName evidence="62"CRAF1 alternativeName: fullName evidence="61"CD40-binding protein shortName evidence="61"CD40BP alternativeName: fullName evidence="63"LMP1-associated protein 1 shortName evidence="63"LAP1 alternativeName: fullName evidence="64"RING-type E3 ubiquitin transferase TRAF3 |
| geneName | TRAF3 CAP-1 CRAF1 TRAFAMN |
| identifier | Q13114 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Apoptosis Coiled coil Cytoplasm Disease variant Endosome Host-virus interaction Immunity Isopeptide bond Metal-binding Mitochondrion Phosphoprotein Proteomics identification Reference proteome Repeat Thioester bond Transferase Ubl conjugation Ubl conjugation pathway Zinc Zinc-finger |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | TRAF3 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8992212] ENSEMBL:ENSG00000131323 TRAF3 [Homo sapiens] |
| secondaryIdentifier | TRAF3_HUMAN B7Z8C4 Q12990 Q13076 Q13947 Q6AZX1 Q9UNL1 |
| sequenceLength | 568 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:8969023] UniProt:Q13114-1 TRAF3 [Homo sapiens] [ReferenceIsoform:8969024] UniProt:Q13114-2 TRAF3 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:914241] TRAF3 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:936402] K63polyUb-TRAF3 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:936556] K48polyUb-TRAF3 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:5602321] TRAF3 R118W [cytosol] [Homo sapiens] |
| (referenceSequence) | [GroupModifiedResidue:3080575] ubiquitinylated lysine (K48polyUb [cytosol]) at unknown position [GroupModifiedResidue:3080587] ubiquitinylated lysine (K63-polyubiquitin [cytosol]) at unknown position [ReplacedResidue:5602673] L-arginine 118 replaced with L-tryptophan |
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No pathways have been reviewed or authored by UniProt:Q13114 TRAF3 (66373)
