Traf3
entrez
22031
canonical
uniprot
Q60803
canonical
ensembl
ENSMUSG00000021277
resolver
ensp
ENSMUSP00000021706
resolver
ensp
ENSMUSP00000058361
resolver
ensp
ENSMUSP00000112517
resolver
ensp
ENSMUSP00000236961
resolver
ensp
ENSMUSP00000236962
resolver
ensp
ENSMUSP00000236966
resolver
ensp
ENSMUSP00000339767
resolver
enst
ENSMUST00000021706
resolver
enst
ENSMUST00000060274
resolver
enst
ENSMUST00000117269
resolver
genesymbol
Traf3
resolver
genesymbol_syn
Cap-1
resolver
genesymbol_syn
Craf1
resolver
genesymbol_syn
Trafamn
resolver
uniprot
B2RPW3
resolver
uniprot
F6SVF1
resolver
uniprot
Q3UHJ1
resolver
uniprot
Q62380
resolver
uniprot_entry
F6SVF1_MOUSE
resolver
uniprot_entry
Q3UHJ1_MOUSE
resolver
uniprot_entry
TRAF3_MOUSE
resolver
uniprot_sec
B2RPW3
resolver
uniprot_sec
Q62380
resolver
amino_acid_sequence
MESSKKMDAAGTLQPNPPLKLQPDRGAGSVLVPEQGGYKEKFVKTVEDKYKCEKCRLVLCNPKQTECGHRFCESCMAALLSSSSPKCTACQESIIKDKVFKDNCCKREILALQVYCRNEGRGCAEQLTLGHLLVHLKNECQFEELPCLRADCKEKVLRKDLRDHVEKACKYREATCSHCKSQVPMIKLQKHEDTDCPCVVVSCPHKCSVQTLLRSELSAHLSECVNAPSTCSFKRYGCVFQGTNQQIKAHEASSAVQHVNLLKEWSNSLEKKVSLLQNESVEKNKSIQSLHNQICSFEIEIERQKEMLRNNESKILHLQRVIDSQAEKLKELDKEIRPFRQNWEEADSMKSSVESLQNRVTELESVDKSAGQAARNTGLLESQLSRHDQMLSVHDIRLADMDLRFQVLETASYNGVLIWKIRDYKRRKQEAVMGKTLSLYSQPFYTGYFGYKMCARVYLNGDGMGKGTHLSLFFVIMRGEYDALLPWPFKQKVTLMLMDQGSSRRHLGDAFKPDPNSSSFKKPTGEMNIASGCPVFVAQTVLENGTYIKDDTIFIKVIVDTSDLPDP
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:17015635). 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:19898473, PubMed:23150880, PubMed:23871208, PubMed:26305951). 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 (PubMed:16306937). 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. Also acts as a constitutive negative regulator of the alternative NF-kappa-B pathway, which controls B-cell survival and lymphoid organ development (PubMed:17723217). Required for normal antibody isotype switching from IgM to IgG (PubMed:19228877). Plays a role T-cell dependent immune responses (PubMed:8934568). 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:16306936, ECO:0000269|PubMed:16306937, ECO:0000269|PubMed:17015635, ECO:0000269|PubMed:17158868, ECO:0000269|PubMed:17723217, ECO:0000269|PubMed:18313334, ECO:0000269|PubMed:18997792, ECO:0000269|PubMed:18997794, ECO:0000269|PubMed:19228877, ECO:0000269|PubMed:19898473, ECO:0000269|PubMed:26305951, ECO:0000269|PubMed:26474655, ECO:0000269|PubMed:30579117, ECO:0000269|PubMed:8934568}.
uniprot
proteins
mass_dalton
64294
uniprot
proteins
mutagenesis
MUTAGEN 52; /note="C->A: Abolishes inhibition of NFKB2 processing; when associated with A-55."; /evidence="ECO:0000269|PubMed:17158868"; MUTAGEN 55; /note="C->A: Abolishes inhibition of NFKB2 processing; when associated with A-52."; /evidence="ECO:0000269|PubMed:17158868"; MUTAGEN 67; /note="C->A: Strongly reduces 'Lys-63'-linked ubiquitination; when associated with A-69. Abolishes inhibition of NFKB2 processing; when associated with A-69."; /evidence="ECO:0000269|PubMed:17158868, ECO:0000269|PubMed:19898473"; MUTAGEN 69; /note="H->A: Strongly reduces 'Lys-63'-linked ubiquitination; when associated with A-69. Abolishes inhibition of NFKB2 processing; when associated with A-67."; /evidence="ECO:0000269|PubMed:17158868, ECO:0000269|PubMed:19898473"; MUTAGEN 106; /note="K->R: Reduces 'Lys-48'-linked polyubiquitination; when associated with R-155."; /evidence="ECO:0000269|PubMed:19898473"; MUTAGEN 155; /note="K->R: Reduces 'Lys-48'-linked polyubiquitination; when associated with R-106."; /evidence="ECO:0000269|PubMed:19898473"; MUTAGEN 328; /note="K->R: Abolished ubiquitination by the SCF(FBXL2) complex."; /evidence="ECO:0000269|PubMed:23542741"; MUTAGEN 419; /note="W->A: Decreased interaction with FBXL2."; /evidence="ECO:0000269|PubMed:23542741"; MUTAGEN 440; /note="Y->F: Loss of interaction with MAVS."; /evidence="ECO:0000269|PubMed:23150880"; MUTAGEN 473; /note="F->Y: Loss of interaction with MAVS."; /evidence="ECO:0000269|PubMed:23150880
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 (PubMed:19898473). 'Lys-48'-linked polyubiquitinated form is deubiquitinated by OTUD7B, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B (PubMed:23334419). 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 (PubMed:26474655). Ubiquitinated at Lys-328 by the SCF(FBXL2) complex, leading to its degradation by the proteasome (PubMed:23542741). {ECO:0000269|PubMed:18997792, ECO:0000269|PubMed:19898473, ECO:0000269|PubMed:23334419, ECO:0000269|PubMed:23542741, ECO:0000269|PubMed:26474655}.; 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-55 and Cys-123 by NEDD4L; leading to increased 'Lys-48'- and 'Lys-63'-linked ubiquitination as well as increased binding to TBK1. 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 (By similarity). Deubiquitinated by USP25 during viral infection, leading to TRAF3 stabilization and type I interferon production (PubMed:26305951). 'Lys-63'-linked ubiquitination by FBXO11 in a NEDD8-dependent manner promotes the amplification of IFN-I signaling (By similarity). {ECO:0000250|UniProtKB:Q13114, ECO:0000269|PubMed:18997792, ECO:0000269|PubMed:19898473, ECO:0000269|PubMed:23334419, ECO:0000269|PubMed:26305951, ECO:0000269|PubMed:26474655, ECO:0000269|PubMed:30579117}.
uniprot
proteins
protein_family
A subfamily
uniprot
proteins
protein_family
TNF receptor-associated factor family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16306936
uniprot
proteins
pubmed
16306937
uniprot
proteins
pubmed
17015635
uniprot
proteins
pubmed
17158868
uniprot
proteins
pubmed
17723217
uniprot
proteins
pubmed
18313334
uniprot
proteins
pubmed
18849341
uniprot
proteins
pubmed
18997792
uniprot
proteins
pubmed
18997794
uniprot
proteins
pubmed
19228877
uniprot
proteins
pubmed
19898473
uniprot
proteins
pubmed
23150880
uniprot
proteins
pubmed
23334419
uniprot
proteins
pubmed
23542741
uniprot
proteins
pubmed
23871208
uniprot
proteins
pubmed
26029823
uniprot
proteins
pubmed
26305951
uniprot
proteins
pubmed
26474655
uniprot
proteins
pubmed
30579117
uniprot
proteins
pubmed
7533327
uniprot
proteins
pubmed
8660894
uniprot
proteins
pubmed
8934568
uniprot
proteins
sequence_length
567
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19898473}. Endosome {ECO:0000269|PubMed:19898473}. Mitochondrion {ECO:0000250|UniProtKB:Q13114}. Note=Undergoes endocytosis together with TLR4 upon LPS signaling (PubMed:19898473). Co-localized to mitochondria with TRIM35 (By similarity). {ECO:0000250|UniProtKB:Q13114, ECO:0000269|PubMed:19898473}.
uniprot
proteins