UniProt:Q12933 TRAF2

  • initiator methionine:1
  • chain:2-501
checksum C508BE185B783B20
  • FUNCTION Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'-linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. 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. 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. Plays a role in mediating activation of NF-kappa-B by EIF2AK2/PKR. In complex with BIRC2 or BIRC3, promotes ubiquitination of IKBKE.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.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Homotrimer (PubMed:8069916). Heterotrimer with TRAF1 (PubMed:8069916). Heterotrimer with TRAF3 (via TRAF domain) (PubMed:15383523, PubMed:20447407). The domain containing the RING-type and the first TRAF-type zinc finger can also form homodimers (in vitro) (PubMed:19810754). Interacts with TNFRSF1B/TNFR2 (PubMed:7639698, PubMed:8069916, PubMed:10206649). Interacts with TNFRSF5/CD40 (PubMed:9718306). Interacts with TNFRSF4, TNFRSF7/CD27, TNFRSF8/CD30, TNFRSF9/CD137, TNFRSF11A/RANK, TNFRSF13B/TACI, TNFRSF14, TNFRSF16/NGFR, TNFRSF17/BCMA, TNFRSF18/AITR, TNFRSF19/TROY, TNFRSF19L/RELT and EDAR (PubMed:8627180, PubMed:9153189, PubMed:9692890, PubMed:9488716, PubMed:9774460, PubMed:9607925, PubMed:9418902, PubMed:10037686, PubMed:10514511, PubMed:10809768, PubMed:10880535, PubMed:11035039, PubMed:10411888). Stimulation of TNF-alpha receptor TNFRSF1A leads to the formation of two distinct signaling complexes. Plasma membrane-bound complex I is composed of TNFRSF1A, TRADD, RIPK1, TRAF2 and BIRC2/c-IAP1 or BIRC3 which interacts with CHUCK/IKK-alpha, IKBKB/IKK-beta and IKBKG/IKK-gamma promoting cell survival (PubMed:21307340, PubMed:18981220). Subsequently, TRADD, RIPK1 and TRAF2 dissociate from TNFRSF1A and form cytoplasmic complex II with FADD and caspase CASP8 promoting cell apoptosis (PubMed:21307340). Interacts with TRADD (PubMed:10892748). Identified in a complex with TNFRSF1A, RIPK1 and IKBKB/IKK-beta (PubMed:18981220). Interacts with RIPK2 (PubMed:9705938). Interacts with BIRC2 and BIRC3 N-terminus; a single BIRC2 or BIRC3 molecule interacts with a heterotrimer formed by TRAF1 and TRAF2, or a TRAF2 homotrimer (PubMed:11907583, PubMed:19506082, PubMed:20447407, PubMed:20385093). Identified in a complex composed of TRAF2, TRAF3, BIRC2 and BIRC3 (By similarity). Interacts with BIRC2; the interaction promotes BIRC2 stability (PubMed:19506082). Interaction with BIRC2 and/or BIRC3 is essential for ubiquitination of IKBKE, degradation of NFKBIA and activation of NF-kappa-B (By similarity). Within complex I, phosphorylated TRAF2 interacts (via 'Lys-63'-linked polyubiquitin chains) with CHUCK/IKK-alpha, IKBKB/IKK-beta, IKBKG/IKK-gamma TAB2, TAB3 and TAK1 in response to TNF-alpha stimulation (PubMed:19150425). Within complex I, interacts with UXT isoform 1 (via TPQE motif); the interaction prevents the recruitment of FADD and CASP8/caspase 8 to complex I (PubMed:21307340). Forms a complex composed of TNFRSF8/CD30 or TNFRSF1B/TNFR2, and TRAF1, TRAF2 and E3 ligase TRAIP (PubMed:9104814). Within the complex, interacts with TRAIP; the interaction inhibits TRAF2-mediated NF-kappa B activation (PubMed:9104814). Component of a complex composed of TANK and TBK1 (PubMed:10581243). Interacts with TRPC4AP (By similarity). Interacts with MAP3K1/MEKK1, MAP3K5/ASK1 and MAP3K11/MLK3 in response to TNF-alpha stimulation; the interaction leads to JNK activation (PubMed:10346818, PubMed:19918265, PubMed:9774977). Component of a complex composed of MAP3K14/NIK BIRC3 and TRAF3; the interaction leads to BIRC2/3-mediated ubiquitination of TRAF3 upon CD40 engagement in a TRAF2-dependent manner (By similarity). Interacts with MAP3K14/NIK in response to TNF-alpha stimulation; the interaction leads to NF-kappa B activation (PubMed:9020361). Interacts with PEG3; the interaction may promote TRAF2-mediated NF-kappa B activation (By similarity). Interacts with HIVEP3; the interaction may inhibit TNF-alpha-TRAF2-mediated NF-kappa B and JNK activation (By similarity). Interacts with TANK/ITRAF; the interaction prevents interaction between TNFRSF1B/TNFR2 and TRAF2 (PubMed:8710854). Interacts with deubiquitinating enzyme CYLD; the interaction results in the deubiquitination and inactivation of TRAF2 (PubMed:12917691). Interacts with SIAH2; the interaction leads to TRAF2 ubiquitination and degradation (PubMed:12411493). Interacts with E2 conjugating enzyme UBE2N/Ubc13, E3 ligase ITCH and RNF11 in response to TNF-alpha stimulation (By similarity). Interacts with ubiquitin-editing enzyme TNFAIP3/A20 in response to TNF-alpha stimulation; the interaction promotes TRAF2 dissociation from UBE2N/Ubc13, ITCH, RNF11 and TAX1BP1 and prevents prolonged TRAF-2 ubiquitination (By similarity). Interacts with TAX1BP1 in response to TNF-alpha stimulation; the interaction promotes TRAF2 dissociation from UBE2N/Ubc13 and TNFAIP3/A20, and prevents prolonged TRAF-2 ubiquitination (By similarity). Interacts (via C-terminus) with EIF2AK2/PKR (via the kinase catalytic domain) (PubMed:15121867). Interacts with deubiquitinating enzyme USP48 (PubMed:16214042). Interacts with PTPN2; probably involved in TNF-mediated signaling (PubMed:15696169). Interacts with Toll-like receptor TLR4/3 adapter TICAM1/TRIF; the interaction may promote TICAM1 ubiquitination (PubMed:20047764). Interacts with kinase/endoribonuclease ERN1/IRE1 and DAB2IP in response to ER stress; the interaction requires DAB2IP (By similarity). Interacts with ERN1/IRE1 and TAOK3 in response to ER stress; the interaction may promote TRAF2 phosphorylation (PubMed:11278723). Interacts (via zinc fingers) with DAB2IP (via C-terminus PER domain)in response to TNF-alpha stimulation (PubMed:15310755, PubMed:17389591). Interacts with CASP8AP2/FLASH (By similarity). Interacts with NFATC2IP; the interaction may repress IL-4 production in T cells (By similarity). Interacts with kinase CDK9 (PubMed:9827693). Interacts with sphingosine kinase 1 SPHK1 (PubMed:20577214). Interacts with kinase TNIK (PubMed:10521462). Interacts with TRAFD1 (By similarity). Interacts with DNA phosphodiesterase TDP2 (PubMed:10764746). Interacts with MAVS/IPS1 (PubMed:16153868). Interacts with CARD14 (PubMed:21302310). Interacts with Epstein-Barr virus LMP1/BNFL1 (PubMed:10411888). Interacts with GPS2 (By similarity). Interacts with XPNPEP3 (PubMed:25609706). Interacts with RIPK3 (PubMed:29883609). Interacts with RELL2 (PubMed:19969290). Interacts with LRRC19 (PubMed:25026888). Interacts with GAPDH; promoting TRAF2 ubiquitination (PubMed:23332158).DOMAIN The coiled coil domain mediates homo- and hetero-oligomerization.DOMAIN The MATH/TRAF domain binds to receptor cytoplasmic domains.DOMAIN The RING-type zinc finger domain is essential for E3 ubiquitin-protein ligase activity. It is not essential for the stabilization of BIRC2, or for the ubiquitination of RIPK1 in response to TNFR1 signaling.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.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. Ubiquination is inhibited by LRRC19; inhibits proteasomal degradation (PubMed:25026888).SIMILARITY Belongs to the TNF receptor-associated factor family. A subfamily.CAUTION Was reported to interact with IL15RA (PubMed:10463949). However, this work was later retracted (PubMed:21357251).
databaseName UniProt
dbId 66371
  • recommendedName: TNF receptor-associated factor 2 ecNumber2.3.2.27/ecNumber alternativeName: E3 ubiquitin-protein ligase TRAF2 alternativeName: fullName evidence="68"RING-type E3 ubiquitin transferase TRAF2 alternativeName: Tumor necrosis factor type 2 receptor-associated protein 3
displayName UniProt:Q12933 TRAF2
  • TRAF2
  • TRAP3
identifier Q12933
isSequenceChanged false
  • 3D-structure
  • Acetylation
  • Alternative splicing
  • Apoptosis
  • Coiled coil
  • Cytoplasm
  • Isopeptide bond
  • Lipid-binding
  • Metal-binding
  • Phosphoprotein
  • Reference proteome
  • Repeat
  • Transferase
  • Ubl conjugation
  • Ubl conjugation pathway
  • Zinc
  • Zinc-finger
modified [InstanceEdit:11703169] Weiser, JD, 2021-09-15
  • TRAF2
  • 0000610397
  • 0001450091
  • 11749036_a_at
  • 11754185_a_at
  • 17091444
  • 1746_s_at
  • 204413_at
  • 3194905
  • 3194916
  • 3194917
  • 3194918
  • 3194919
  • 3194920
  • 3194928
  • 3194930
  • 3194937
  • 3194943
  • 3194944
  • 3194945
  • 3194946
  • 3194950
  • 3194951
  • 3194952
  • 3194953
  • 3194954
  • 3194955
  • 33784_at
  • 7186
  • 8159476
  • A_14_P103294
  • A_23_P169331
  • A_33_P3424295
  • A_33_P3803639
  • GE82592
  • GO:0000151
  • GO:0002376
  • GO:0002637
  • GO:0002726
  • GO:0002947
  • GO:0003674
  • GO:0004842
  • GO:0005164
  • GO:0005174
  • GO:0005515
  • GO:0005575
  • GO:0005622
  • GO:0005634
  • GO:0005654
  • GO:0005737
  • GO:0005783
  • GO:0005829
  • GO:0005886
  • GO:0005938
  • GO:0006464
  • GO:0006915
  • GO:0006919
  • GO:0006950
  • GO:0007165
  • GO:0007249
  • GO:0007250
  • GO:0008150
  • GO:0008219
  • GO:0008270
  • GO:0008289
  • GO:0009056
  • GO:0009058
  • GO:0009898
  • GO:0010803
  • GO:0012506
  • GO:0016567
  • GO:0016579
  • GO:0016740
  • GO:0019899
  • GO:0019901
  • GO:0019903
  • GO:0022607
  • GO:0023019
  • GO:0030163
  • GO:0030674
  • GO:0031435
  • GO:0031625
  • GO:0031996
  • GO:0032743
  • GO:0032991
  • GO:0033209
  • GO:0034351
  • GO:0034622
  • GO:0034641
  • GO:0034655
  • GO:0034976
  • GO:0035631
  • GO:0042802
  • GO:0042981
  • GO:0043120
  • GO:0043122
  • GO:0043123
  • GO:0043167
  • GO:0043226
  • GO:0043254
  • GO:0043507
  • GO:0044877
  • GO:0045121
  • GO:0046328
  • GO:0046330
  • GO:0046625
  • GO:0046872
  • GO:0048255
  • GO:0051091
  • GO:0051092
  • GO:0051865
  • GO:0065003
  • GO:0070059
  • GO:0070534
  • GO:0071550
  • GO:0071732
  • GO:0097057
  • GO:0097300
  • GO:0097400
  • GO:1901215
  • GO:1902041
  • GO:1902042
  • GO:1903265
  • GO:1903721
  • GO:1990604
  • GO:2001238
  • HMNXSV003054154
  • ILMN_1691487
  • PH_hs_0020685
  • TC09000826.hg
  • g10863938_3p_at
referenceDatabase [ReferenceDatabase:2] UniProt
schemaClass ReferenceGeneProduct
  • A8K107
  • B4DPJ7
  • Q7Z337
  • Q96NT2
sequenceLength 501
species [Species:48887] Homo sapiens
url http://purl.uniprot.org/uniprot/Q12933


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