TRAF3
entrez
7187
canonical
uniprot
Q13114
canonical
ensembl
ENSG00000131323
resolver
ensp
ENSP00000332468
resolver
ensp
ENSP00000376500
resolver
ensp
ENSP00000445998
resolver
ensp
ENSP00000454207
resolver
ensp
ENSP00000514677
resolver
ensp
ENSP00000514678
resolver
ensp
ENSP00000530973
resolver
ensp
ENSP00000530974
resolver
ensp
ENSP00000530978
resolver
ensp
ENSP00000609133
resolver
ensp
ENSP00000622396
resolver
ensp
ENSP00000622397
resolver
ensp
ENSP00000777772
resolver
enst
ENST00000351691
resolver
enst
ENST00000699893
resolver
enst
ENST00000860914
resolver
enst
ENST00000952337
resolver
enst
ENST00000952338
resolver
genesymbol
TRAF3
resolver
genesymbol_syn
CAP-1
resolver
genesymbol_syn
CRAF1
resolver
genesymbol_syn
TRAFAMN
resolver
hgnc
HGNC:12033
resolver
uniprot
A6NHG8
resolver
uniprot
B7Z8C4
resolver
uniprot
Q12990
resolver
uniprot
Q13076
resolver
uniprot
Q13947
resolver
uniprot
Q6AZX1
resolver
uniprot
Q9UNL1
resolver
uniprot_entry
A6NHG8_HUMAN
resolver
uniprot_entry
TRAF3_HUMAN
resolver
uniprot_sec
B7Z8C4
resolver
uniprot_sec
Q12990
resolver
uniprot_sec
Q13076
resolver
uniprot_sec
Q13947
resolver
uniprot_sec
Q6AZX1
resolver
uniprot_sec
Q9UNL1
resolver
amino_acid_sequence
MESSKKMDSPGALQTNPPLKLHTDRSAGTPVFVPEQGGYKEKFVKTVEDKYKCEKCHLVLCSPKQTECGHRFCESCMAALLSSSSPKCTACQESIVKDKVFKDNCCKREILALQIYCRNESRGCAEQLMLGHLLVHLKNDCHFEELPCVRPDCKEKVLRKDLRDHVEKACKYREATCSHCKSQVPMIALQKHEDTDCPCVVVSCPHKCSVQTLLRSELSAHLSECVNAPSTCSFKRYGCVFQGTNQQIKAHEASSAVQHVNLLKEWSNSLEKKVSLLQNESVEKNKSIQSLHNQICSFEIEIERQKEMLRNNESKILHLQRVIDSQAEKLKELDKEIRPFRQNWEEADSMKSSVESLQNRVTELESVDKSAGQVARNTGLLESQLSRHDQMLSVHDIRLADMDLRFQVLETASYNGVLIWKIRDYKRRKQEAVMGKTLSLYSQPFYTGYFGYKMCARVYLNGDGMGKGTHLSLFFVIMRGEYDALLPWPFKQKVTLMLMDQGSSRRHLGDAFKPDPNSSSFKKPTGEMNIASGCPVFVAQTVLENGTYIKDDTIFIKVIVDTSDLPDP
uniprot
proteins
disease_involvement
DISEASE: Immunodeficiency 132A (IMD132A) [MIM:614849]: An autosomal dominant immunologic disorder characterized by increased susceptibility to infection with certain pathogens, including Herpes simplex virus and Mycobacterium abscessus. Immunologic work-up shows impaired production of cytokines, including INFB and IL6. {ECO:0000269|PubMed:20832341, ECO:0000269|PubMed:36004314}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Immunodeficiency 132B (IMD132B) [MIM:621096]: An autosomal dominant immune disorder characterized by childhood onset of recurrent upper and lower respiratory infections, B-cell lymphoid hyperplasia, and dysregulation of T-cell subsets and function. Additional variable features include autoimmunity, autoinflammation, and hyper- or hypogammaglobulinemia. {ECO:0000269|PubMed:35960817, ECO:0000269|PubMed:39579173}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
function
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. {ECO:0000269|PubMed:15084608, ECO:0000269|PubMed:15383523, ECO:0000269|PubMed:17991829, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:20097753, ECO:0000269|PubMed:20185819, ECO:0000269|PubMed:25847972, ECO:0000269|PubMed:27980081, ECO:0000269|PubMed:32562145, ECO:0000269|PubMed:33148796, ECO:0000269|PubMed:33608556, ECO:0000269|PubMed:34011520}.
uniprot
proteins
mass_dalton
64490
uniprot
proteins
mutagenesis
MUTAGEN 56; /note="C->A: Strong increase in both 'Lys-48' and 'Lys-63'-linked ubiquitination."; /evidence="ECO:0000269|PubMed:33608556"; MUTAGEN 68..70; /note="CGH->AGA: Loss of ubiquitination activity, impaired interaction with MAVS and IRF3. No effect on interaction with IKBKE, nor with DDX3X."; /evidence="ECO:0000269|PubMed:27980081"; MUTAGEN 68; /note="C->A: Loss of ubiquitination activity on ASC; when associated with A-70."; /evidence="ECO:0000269|PubMed:25847972"; MUTAGEN 70; /note="H->A: Loss of ubiquitination activity on ASC; when associated with A-68."; /evidence="ECO:0000269|PubMed:25847972"; MUTAGEN 124; /note="C->A: Strong increase in both 'Lys-48' and 'Lys-63'-linked ubiquitination."; /evidence="ECO:0000269|PubMed:33608556"; MUTAGEN 168; /note="K->R: Abolishes interaction with RALGDS."; /evidence="ECO:0000269|PubMed:27438768"; MUTAGEN 441; /note="Y->A: Abolishes interaction with RNF216; when associated with A-443."; /evidence="ECO:0000269|PubMed:19893624"; MUTAGEN 443; /note="Q->A: Abolishes interaction with RNF216; when associated with A-441."; /evidence="ECO:0000269|PubMed:19893624"; MUTAGEN 459; /note="Y->A: Abolishes interaction with LTBR, CD40 and TANK."; /evidence="ECO:0000269|PubMed:14517219"; MUTAGEN 462; /note="G->A: Confers resistance to cleavage by enterovirus D68 protease 2A."; /evidence="ECO:0000269|PubMed:33148796"; MUTAGEN 512; /note="F->E: Abolishes interaction with LTBR, CD40 and TANK."; /evidence="ECO:0000269|PubMed:14517219"; MUTAGEN 521; /note="F->A: Abolishes interaction with LTBR, CD40 and TANK."; /evidence="ECO:0000269|PubMed:14517219
uniprot
proteins
post_translational_modification
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). {ECO:0000250|UniProtKB:Q60803, ECO:0000269|PubMed:17991829, ECO:0000269|PubMed:19893624, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:19996094, ECO:0000269|PubMed:20097753, ECO:0000269|PubMed:27438768, ECO:0000269|PubMed:27980081, ECO:0000269|PubMed:32562145, ECO:0000269|PubMed:33608556, ECO:0000269|PubMed:34011520, ECO:0000269|PubMed:36897010}.; PTM: (Microbial infection) Cleaved by enterovirus D68 protease 2A; leading to inhibition of NF-kappa-B or IFN-beta triggered by TRAF3. {ECO:0000269|PubMed:33148796}.
uniprot
proteins
protein_family
A subfamily
uniprot
proteins
protein_family
TNF receptor-associated factor family
uniprot
proteins
pubmed
10037686
uniprot
proteins
pubmed
10199393
uniprot
proteins
pubmed
10523862
uniprot
proteins
pubmed
10764746
uniprot
proteins
pubmed
10791955
uniprot
proteins
pubmed
10809768
uniprot
proteins
pubmed
10903733
uniprot
proteins
pubmed
10984535
uniprot
proteins
pubmed
11035039
uniprot
proteins
pubmed
12005438
uniprot
proteins
pubmed
12508121
uniprot
proteins
pubmed
14517219
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15084608
uniprot
proteins
pubmed
15383523
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15585864
uniprot
proteins
pubmed
16009714
uniprot
proteins
pubmed
17991829
uniprot
proteins
pubmed
18614628
uniprot
proteins
pubmed
19419966
uniprot
proteins
pubmed
19893624
uniprot
proteins
pubmed
19937093
uniprot
proteins
pubmed
19996094
uniprot
proteins
pubmed
20097753
uniprot
proteins
pubmed
20174559
uniprot
proteins
pubmed
20185819
uniprot
proteins
pubmed
20832341
uniprot
proteins
pubmed
21302310
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23871208
uniprot
proteins
pubmed
24390324
uniprot
proteins
pubmed
25847972
uniprot
proteins
pubmed
27387501
uniprot
proteins
pubmed
27438768
uniprot
proteins
pubmed
27980081
uniprot
proteins
pubmed
32562145
uniprot
proteins
pubmed
33148796
uniprot
proteins
pubmed
33608556
uniprot
proteins
pubmed
34011520
uniprot
proteins
pubmed
35960817
uniprot
proteins
pubmed
36004314
uniprot
proteins
pubmed
36897010
uniprot
proteins
pubmed
39579173
uniprot
proteins
pubmed
7527023
uniprot
proteins
pubmed
7530216
uniprot
proteins
pubmed
7533327
uniprot
proteins
pubmed
7859281
uniprot
proteins
pubmed
8663299
uniprot
proteins
pubmed
8710854
uniprot
proteins
pubmed
9162022
uniprot
proteins
pubmed
9168896
uniprot
proteins
pubmed
9275204
uniprot
proteins
pubmed
9418902
uniprot
proteins
pubmed
9488716
uniprot
proteins
pubmed
9718306
uniprot
proteins
pubmed
9774460
uniprot
proteins
pubmed
9774977
uniprot
proteins
sequence_length
568
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25847972, ECO:0000269|PubMed:34011520}. Endosome {ECO:0000250|UniProtKB:Q60803}. Mitochondrion {ECO:0000269|PubMed:32562145}. Note=Undergoes endocytosis together with TLR4 upon LPS signaling (By similarity). Co-localized to mitochondria with TRIM35 (PubMed:32562145). {ECO:0000250|UniProtKB:Q60803, ECO:0000269|PubMed:32562145}.
uniprot
proteins