TRAF2
entrez
7186
canonical
uniprot
Q12933
canonical
ensembl
ENSG00000127191
resolver
ensp
ENSP00000247668
resolver
ensp
ENSP00000552612
resolver
ensp
ENSP00000552621
resolver
ensp
ENSP00000552633
resolver
genesymbol
TRAF2
resolver
genesymbol_syn
TRAP3
resolver
hgnc
HGNC:12032
resolver
uniprot
A8K107
resolver
uniprot
B4DPJ7
resolver
uniprot
Q7Z337
resolver
uniprot
Q96NT2
resolver
uniprot_entry
TRAF2_HUMAN
resolver
uniprot_sec
A8K107
resolver
uniprot_sec
B4DPJ7
resolver
uniprot_sec
Q7Z337
resolver
uniprot_sec
Q96NT2
resolver
activity_regulation
ACTIVITY REGULATION: Has very low E3 ubiquitin ligase activity in the absence of sphingosine-1-phosphate. E3 ubiquitin ligase activity is strongly activated by cytoplasmic sphingosine-1-phosphate. {ECO:0000269|PubMed:20577214}.
uniprot
proteins
amino_acid_sequence
MAAASVTPPGSLELLQPGFSKTLLGTKLEAKYLCSACRNVLRRPFQAQCGHRYCSFCLASILSSGPQNCAACVHEGIYEEGISILESSSAFPDNAARREVESLPAVCPSDGCTWKGTLKEYESCHEGRCPLMLTECPACKGLVRLGEKERHLEHECPERSLSCRHCRAPCCGADVKAHHEVCPKFPLTCDGCGKKKIPREKFQDHVKTCGKCRVPCRFHAIGCLETVEGEKQQEHEVQWLREHLAMLLSSVLEAKPLLGDQSHAGSELLQRCESLEKKTATFENIVCVLNREVERVAMTAEACSRQHRLDQDKIEALSSKVQQLERSIGLKDLAMADLEQKVLEMEASTYDGVFIWKISDFARKRQEAVAGRIPAIFSPAFYTSRYGYKMCLRIYLNGDGTGRGTHLSLFFVVMKGPNDALLRWPFNQKVTLMLLDQNNREHVIDAFRPDVTSSSFQRPVNDMNIASGCPLFCPVSKMEAKNSYVRDDAIFIKAIVDLTGL
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
function
FUNCTION: E3 ubiquitin-protein ligase that regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis (PubMed:10346818, PubMed:11784851, PubMed:12917689, PubMed:15383523, PubMed:18981220, PubMed:19150425, PubMed:19810754, PubMed:19918265, PubMed:19937093, PubMed:20047764, PubMed:20064526, PubMed:20385093, PubMed:20577214, PubMed:22212761). Catalyzes 'Lys-63'-linked ubiquitination of target proteins, such as BIRC3, IKBKE, MLST8, RIPK1 and TICAM1 (PubMed:23453969, PubMed:28489822). Is an essential constituent of several E3 ubiquitin-protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases (PubMed:15383523, PubMed:18981220). Regulates BIRC2 and BIRC3 protein levels by inhibiting their autoubiquitination and subsequent degradation; this does not depend on the TRAF2 RING-type zinc finger domain (PubMed:11907583, PubMed:19506082). Plays a role in mediating activation of NF-kappa-B by EIF2AK2/PKR (PubMed:15121867). In complex with BIRC2 or BIRC3, promotes ubiquitination of IKBKE (PubMed:23453969). Acts as a regulator of mTORC1 and mTORC2 assembly by mediating 'Lys-63'-linked ubiquitination of MLST8, thereby inhibiting formation of the mTORC2 complex, while facilitating assembly of the mTORC1 complex (PubMed:28489822). Required for normal antibody isotype switching from IgM to IgG (By similarity). {ECO:0000250|UniProtKB:P39429, ECO:0000269|PubMed:10346818, ECO:0000269|PubMed:11784851, ECO:0000269|PubMed:11907583, ECO:0000269|PubMed:12917689, ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15383523, ECO:0000269|PubMed:18981220, ECO:0000269|PubMed:19150425, ECO:0000269|PubMed:19506082, ECO:0000269|PubMed:19810754, ECO:0000269|PubMed:19918265, ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:20047764, ECO:0000269|PubMed:20064526, ECO:0000269|PubMed:20385093, ECO:0000269|PubMed:20577214, ECO:0000269|PubMed:22212761, ECO:0000269|PubMed:23453969, ECO:0000269|PubMed:28489822}.
uniprot
proteins
mass_dalton
55859
uniprot
proteins
mutagenesis
MUTAGEN 11; /note="S->A: Reduces global phosphorylation. Partial reduction of TNF-dependent activation of NF-kappa-B and activation of JNK."; /evidence="ECO:0000269|PubMed:18981220"; MUTAGEN 11; /note="S->D: Slight increase of TNF-dependent activation of NF-kappa-B and activation of JNK."; /evidence="ECO:0000269|PubMed:18981220"; MUTAGEN 31; /note="K->R: Abolishes 'Lys-63'-linked polyubiquitination."; MUTAGEN 117; /note="T->A: Loss of phosphorylation site. Abolishes activation of NF-kappa-B."; /evidence="ECO:0000269|PubMed:19150425"; MUTAGEN 285; /note="I->A: Strongly reduced interaction with BIRC3."; /evidence="ECO:0000269|PubMed:20385093"; MUTAGEN 288; /note="V->A: Strongly reduced interaction with BIRC3."; /evidence="ECO:0000269|PubMed:20385093"; MUTAGEN 292; /note="E->A: Strongly reduced interaction with BIRC3."; /evidence="ECO:0000269|PubMed:20385093
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:28489822}.
uniprot
proteins
post_translational_modification
PTM: Phosphorylated at several serine residues within the first 128 amino acid residues. Phosphorylated at Thr-117 in response to signaling via TNF and TNFRSF1A. Phosphorylation at Thr-117 is required for 'Lys-63'-linked polyubiquitination, but not for 'Lys-48'-linked polyubiquitination. Phosphorylation at Thr-117 is important for interaction with IKKA and IKKB, activation of IKK and subsequent activation of NF-kappa-B. {ECO:0000269|PubMed:19150425}.; PTM: Undergoes both 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination. Polyubiquitinated via 'Lys-63'-linked ubiquitin in response to TNF signaling; this requires prior phosphorylation at Thr-117. 'Lys-63'-linked polyubiquitination promotes TRAF2-mediated activation of NF-kappa-B. Can be polyubiquitinated at several Lys residues via 'Lys-48'-linked ubiquitin chains in response to TNF signaling, leading to proteasomal degradation. Autoubiquitinated, leading to its subsequent proteasomal degradation. Polyubiquitinated by BIRC2 and SIAH2, leading to its subsequent proteasomal degradation. Deubiquitinated by CYLD, a protease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Ubiquitination is inhibited by LRRC19; inhibits proteasomal degradation (PubMed:25026888). Ubiquitinated at Lys-320 by the SCF(FBXL2) complex, leading to its degradation by the proteasome (By similarity). Ubiquitinated by E3 ubiquitin-protein ligase complex containing FBXO7; leading to repression of NF-kappa-B signaling (PubMed:22212761). {ECO:0000250|UniProtKB:P39429, ECO:0000269|PubMed:19150425, ECO:0000269|PubMed:22212761, ECO:0000269|PubMed:25026888}.
uniprot
proteins
protein_family
A subfamily
uniprot
proteins
protein_family
TNF receptor-associated factor family
uniprot
proteins
pubmed
10037686
uniprot
proteins
pubmed
10206649
uniprot
proteins
pubmed
10346818
uniprot
proteins
pubmed
10411888
uniprot
proteins
pubmed
10463949
uniprot
proteins
pubmed
10514511
uniprot
proteins
pubmed
10521462
uniprot
proteins
pubmed
10581243
uniprot
proteins
pubmed
10764746
uniprot
proteins
pubmed
10809768
uniprot
proteins
pubmed
10880535
uniprot
proteins
pubmed
10892748
uniprot
proteins
pubmed
11035039
uniprot
proteins
pubmed
11278723
uniprot
proteins
pubmed
11784851
uniprot
proteins
pubmed
11907583
uniprot
proteins
pubmed
12411493
uniprot
proteins
pubmed
12917689
uniprot
proteins
pubmed
12917691
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15121867
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15310755
uniprot
proteins
pubmed
15383523
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15696169
uniprot
proteins
pubmed
15870263
uniprot
proteins
pubmed
16153868
uniprot
proteins
pubmed
16214042
uniprot
proteins
pubmed
17389591
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18981220
uniprot
proteins
pubmed
19150425
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19506082
uniprot
proteins
pubmed
19810754
uniprot
proteins
pubmed
19918265
uniprot
proteins
pubmed
19937093
uniprot
proteins
pubmed
19969290
uniprot
proteins
pubmed
20047764
uniprot
proteins
pubmed
20064526
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20385093
uniprot
proteins
pubmed
20447407
uniprot
proteins
pubmed
20577214
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21302310
uniprot
proteins
pubmed
21307340
uniprot
proteins
pubmed
21357251
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22095282
uniprot
proteins
pubmed
22212761
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23332158
uniprot
proteins
pubmed
23453969
uniprot
proteins
pubmed
25026888
uniprot
proteins
pubmed
25609706
uniprot
proteins
pubmed
28489822
uniprot
proteins
pubmed
29883609
uniprot
proteins
pubmed
38354704
uniprot
proteins
pubmed
7639698
uniprot
proteins
pubmed
8069916
uniprot
proteins
pubmed
8627180
uniprot
proteins
pubmed
8710854
uniprot
proteins
pubmed
9020361
uniprot
proteins
pubmed
9104814
uniprot
proteins
pubmed
9153189
uniprot
proteins
pubmed
9418902
uniprot
proteins
pubmed
9488716
uniprot
proteins
pubmed
9607925
uniprot
proteins
pubmed
9692890
uniprot
proteins
pubmed
9705938
uniprot
proteins
pubmed
9718306
uniprot
proteins
pubmed
9774460
uniprot
proteins
pubmed
9774977
uniprot
proteins
pubmed
9827693
uniprot
proteins
sequence_length
501
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15383523, ECO:0000269|PubMed:19150425}.
uniprot
proteins