TRAF6
entrez
7189
canonical
uniprot
Q9Y4K3
canonical
ensembl
ENSG00000175104
resolver
ensp
ENSP00000337853
resolver
ensp
ENSP00000433623
resolver
enst
ENST00000348124
resolver
enst
ENST00000526995
resolver
genesymbol
TRAF6
resolver
genesymbol_syn
RNF85
resolver
hgnc
HGNC:12036
resolver
uniprot
A6NKI7
resolver
uniprot
A8KAB3
resolver
uniprot
D3DR16
resolver
uniprot
Q8NEH5
resolver
uniprot_entry
TRAF6_HUMAN
resolver
uniprot_sec
A6NKI7
resolver
uniprot_sec
A8KAB3
resolver
uniprot_sec
D3DR16
resolver
uniprot_sec
Q8NEH5
resolver
amino_acid_sequence
MSLLNCENSCGSSQSESDCCVAMASSCSAVTKDDSVGGTASTGNLSSSFMEEIQGYDVEFDPPLESKYECPICLMALREAVQTPCGHRFCKACIIKSIRDAGHKCPVDNEILLENQLFPDNFAKREILSLMVKCPNEGCLHKMELRHLEDHQAHCEFALMDCPQCQRPFQKFHINIHILKDCPRRQVSCDNCAASMAFEDKEIHDQNCPLANVICEYCNTILIREQMPNHYDLDCPTAPIPCTFSTFGCHEKMQRNHLARHLQENTQSHMRMLAQAVHSLSVIPDSGYISEVRNFQETIHQLEGRLVRQDHQIRELTAKMETQSMYVSELKRTIRTLEDKVAEIEAQQCNGIYIWKIGNFGMHLKCQEEEKPVVIHSPGFYTGKPGYKLCMRLHLQLPTAQRCANYISLFVHTMQGEYDSHLPWPFQGTIRLTILDQSEAPVRQNHEEIMDAKPELLAFQRPTIPRNPKGFGYVTFMHLEALRQRTFIKDDTLLVRCEVSTRFDMGSLRREGFQPRSTDAGV
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
function
FUNCTION: E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as ECSIT, IKBKG, IRAK1, AKT1 and AKT2 (PubMed:11057907, PubMed:18347055, PubMed:19465916, PubMed:19713527, PubMed:27746020, PubMed:31620128). Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation (PubMed:19675569). Leads to the activation of NF-kappa-B and JUN (PubMed:16378096, PubMed:17135271, PubMed:17703191, PubMed:39920527, PubMed:40973797, PubMed:41747053). Seems to also play a role in dendritic cells (DCs) maturation and/or activation (By similarity). Represses c-Myb-mediated transactivation, in B-lymphocytes (PubMed:18093978, PubMed:18758450). Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor (PubMed:12140561, PubMed:19825828, PubMed:8837778). Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation (By similarity). Together with MAP3K8, mediates CD40 signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production (By similarity). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by initiating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: TRAF6 catalyzes initial 'Lys-63'-linked-polyubiquitin chains that are then branched via 'Lys-48'-linked polyubiquitin by HUWE1 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Participates also in the TCR signaling by ubiquitinating LAT (PubMed:23514740, PubMed:25907557). {ECO:0000250|UniProtKB:P70196, ECO:0000269|PubMed:11057907, ECO:0000269|PubMed:12140561, ECO:0000269|PubMed:16378096, ECO:0000269|PubMed:17135271, ECO:0000269|PubMed:17703191, ECO:0000269|PubMed:18093978, ECO:0000269|PubMed:18347055, ECO:0000269|PubMed:18758450, ECO:0000269|PubMed:19465916, ECO:0000269|PubMed:19675569, ECO:0000269|PubMed:19713527, ECO:0000269|PubMed:19825828, ECO:0000269|PubMed:23514740, ECO:0000269|PubMed:25907557, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:31620128, ECO:0000269|PubMed:39920527, ECO:0000269|PubMed:40973797, ECO:0000269|PubMed:41747053, ECO:0000269|PubMed:8837778}.
uniprot
proteins
mass_dalton
59573
uniprot
proteins
mutagenesis
MUTAGEN 57; /note="D->K: Loss of interaction with UBE2N."; /evidence="ECO:0000269|PubMed:19465916"; MUTAGEN 70; /note="C->A: Loss of ligase activity, autoubiquitination and signaling capacity."; /evidence="ECO:0000269|PubMed:17135271, ECO:0000269|PubMed:19465916, ECO:0000269|PubMed:23514740, ECO:0000269|PubMed:27746020"; MUTAGEN 72; /note="I->D: Loss of interaction with UBE2N. Has no effect on TRAF3IP2-mediated 'Lys-63'-linked polyubiquitination."; /evidence="ECO:0000269|PubMed:19465916, ECO:0000269|PubMed:19825828"; MUTAGEN 74; /note="L->E,K: Loss of interaction with UBE2N."; /evidence="ECO:0000269|PubMed:19465916"; MUTAGEN 88; /note="R->A: Loss of TRAF6 homodimerization and impaired polyubiquitin synthesis. Loss of TRAF6 homodimerization and impaired polyubiquitin synthesis; when associated with A-122."; /evidence="ECO:0000269|PubMed:19465916"; MUTAGEN 118; /note="F->A: Loss of TRAF6 homodimerization and impaired polyubiquitin synthesis."; /evidence="ECO:0000269|PubMed:19465916"; MUTAGEN 118; /note="F->W: Partially impaired polyubiquitin synthesis."; /evidence="ECO:0000269|PubMed:19465916"; MUTAGEN 118; /note="F->Y: Partially impaired polyubiquitin synthesis."; /evidence="ECO:0000269|PubMed:19465916"; MUTAGEN 122; /note="F->A: Loss of TRAF6 homodimerization and partially impaired polyubiquitin synthesis. Loss of TRAF6 homodimerization and impaired polyubiquitin synthesis; when associated with A-88."; /evidence="ECO:0000269|PubMed:19465916"; MUTAGEN 124; /note="K->R: Loss of SUMO1-modification and c-myb-mediated transcriptional repressive activation. Loss of TRAF3IP2-mediated 'Lys-63'-linked polyubiquitination."; /evidence="ECO:0000269|PubMed:17135271, ECO:0000269|PubMed:18093978, ECO:0000269|PubMed:19465916, ECO:0000269|PubMed:19825828"; MUTAGEN 142; /note="K->R: Loss of SUMO1-modification and c-myb-mediated transcriptional repressive activation."; /evidence="ECO:0000269|PubMed:18093978"; MUTAGEN 453; /note="K->R: Loss of SUMO1-modification and c-myb-mediated transcriptional repressive activation."; /evidence="ECO:0000269|PubMed:18093978
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:23514740, ECO:0000269|PubMed:27746020}.
uniprot
proteins
post_translational_modification
PTM: Sumoylated on Lys-124, Lys-142 and Lys-453 with SUMO1 (PubMed:18093978). Sumoylated on Lys-453 by TRIM28 in the nucleus, SUMOylation regulates the nucleo-cytoplasmic shuttling of TRAF6 (PubMed:39920527). {ECO:0000269|PubMed:18093978, ECO:0000269|PubMed:39920527}.; PTM: Polyubiquitinated on Lys-124 by TRAF3IP2; after cell stimulation with IL17A (PubMed:19825828). Polyubiquitinated on Lys-124; after cell stimulation with IL1B or TGFB. 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. Deubiquitinated by USP10 in a TANK-dependent manner, leading to the negative regulation of NF-kappaB signaling upon DNA damage (PubMed:25861989). LRRC19 induces 'Lys-63' ubiquitination (PubMed:25026888). Ubiquitinated at Lys-319 by the SCF(FBXL2) complex, leading to its degradation by the proteasome (By similarity). {ECO:0000250|UniProtKB:P70196, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:17135271, ECO:0000269|PubMed:18093978, ECO:0000269|PubMed:18758450, ECO:0000269|PubMed:19465916, ECO:0000269|PubMed:19675569, ECO:0000269|PubMed:19825828, ECO:0000269|PubMed:25026888, ECO:0000269|PubMed:25861989, ECO:0000269|PubMed:31620128}.; PTM: (Microbial infection) Deubiquitinated by Epstein-Barr virus BPLF1 on both 'Lys-48' and 'Lys-63'-linked ubiquitin chains; leading to NF-kappa-B signaling inhibition. {ECO:0000269|PubMed:24586164}.
uniprot
proteins
protein_family
A subfamily
uniprot
proteins
protein_family
TNF receptor-associated factor family
uniprot
proteins
pubmed
10094049
uniprot
proteins
pubmed
10346818
uniprot
proteins
pubmed
10383454
uniprot
proteins
pubmed
10514511
uniprot
proteins
pubmed
10523862
uniprot
proteins
pubmed
10635328
uniprot
proteins
pubmed
10764746
uniprot
proteins
pubmed
10908663
uniprot
proteins
pubmed
10920205
uniprot
proteins
pubmed
11057907
uniprot
proteins
pubmed
11460167
uniprot
proteins
pubmed
11751921
uniprot
proteins
pubmed
11960013
uniprot
proteins
pubmed
12140561
uniprot
proteins
pubmed
12459498
uniprot
proteins
pubmed
12496252
uniprot
proteins
pubmed
12721283
uniprot
proteins
pubmed
12804775
uniprot
proteins
pubmed
12874243
uniprot
proteins
pubmed
14530355
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14739303
uniprot
proteins
pubmed
14754897
uniprot
proteins
pubmed
14982987
uniprot
proteins
pubmed
15121867
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15870274
uniprot
proteins
pubmed
16125763
uniprot
proteins
pubmed
16153868
uniprot
proteins
pubmed
16221674
uniprot
proteins
pubmed
16286016
uniprot
proteins
pubmed
16378096
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16951688
uniprot
proteins
pubmed
17135271
uniprot
proteins
pubmed
17327397
uniprot
proteins
pubmed
17449468
uniprot
proteins
pubmed
17703191
uniprot
proteins
pubmed
18093978
uniprot
proteins
pubmed
18347055
uniprot
proteins
pubmed
18758450
uniprot
proteins
pubmed
19465916
uniprot
proteins
pubmed
19521662
uniprot
proteins
pubmed
19675569
uniprot
proteins
pubmed
19713527
uniprot
proteins
pubmed
19825828
uniprot
proteins
pubmed
20079715
uniprot
proteins
pubmed
20628368
uniprot
proteins
pubmed
21302310
uniprot
proteins
pubmed
21813773
uniprot
proteins
pubmed
23514740
uniprot
proteins
pubmed
23524951
uniprot
proteins
pubmed
23776175
uniprot
proteins
pubmed
24586164
uniprot
proteins
pubmed
25026888
uniprot
proteins
pubmed
25736436
uniprot
proteins
pubmed
25861989
uniprot
proteins
pubmed
25907557
uniprot
proteins
pubmed
27746020
uniprot
proteins
pubmed
28087809
uniprot
proteins
pubmed
31620128
uniprot
proteins
pubmed
39920527
uniprot
proteins
pubmed
40973797
uniprot
proteins
pubmed
41747053
uniprot
proteins
pubmed
8837778
uniprot
proteins
pubmed
9020361
uniprot
proteins
pubmed
9374458
uniprot
proteins
pubmed
9432981
uniprot
proteins
pubmed
9642260
uniprot
proteins
pubmed
9774460
uniprot
proteins
pubmed
9774977
uniprot
proteins
pubmed
9915784
uniprot
proteins
sequence_length
522
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18093978, ECO:0000269|PubMed:23514740, ECO:0000269|PubMed:24586164, ECO:0000269|PubMed:39920527}. Cytoplasm, cell cortex {ECO:0000269|PubMed:18093978}. Nucleus {ECO:0000269|PubMed:18093978, ECO:0000269|PubMed:39920527}. Lipid droplet {ECO:0000250|UniProtKB:P70196}. Note=Found in the nuclei of some aggressive B-cell lymphoma cell lines as well as in the nuclei of both resting and activated T- and B-lymphocytes. Found in punctate nuclear body protein complexes. Ubiquitination may occur in the cytoplasm and sumoylation in the nucleus. RSAD2/viperin recruits it to the lipid droplet (By similarity). {ECO:0000250}.
uniprot
proteins