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Protein

TNF receptor-associated factor 2

Gene

TRAF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.17 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Enzyme regulationi

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.1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri34 – 73RING-typePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri124 – 180TRAF-type 1PROSITE-ProRule annotationAdd BLAST57
Zinc fingeri177 – 233TRAF-type 2PROSITE-ProRule annotationAdd BLAST57

GO - Molecular functioni

  • CD40 receptor binding Source: BHF-UCL
  • enzyme binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • mitogen-activated protein kinase kinase kinase binding Source: Ensembl
  • protein-containing complex binding Source: Ensembl
  • protein kinase binding Source: ParkinsonsUK-UCL
  • protein phosphatase binding Source: UniProtKB
  • sphingolipid binding Source: UniProtKB
  • thioesterase binding Source: UniProtKB
  • tumor necrosis factor receptor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: Reactome
  • activation of NF-kappaB-inducing kinase activity Source: UniProtKB
  • cellular protein-containing complex assembly Source: BHF-UCL
  • cellular response to nitric oxide Source: Ensembl
  • death-inducing signaling complex assembly Source: Reactome
  • I-kappaB kinase/NF-kappaB signaling Source: Reactome
  • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
  • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Reactome
  • negative regulation of glial cell apoptotic process Source: Ensembl
  • negative regulation of neuron death Source: ParkinsonsUK-UCL
  • positive regulation of DNA binding transcription factor activity Source: BHF-UCL
  • positive regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
  • positive regulation of I-kappaB phosphorylation Source: Ensembl
  • positive regulation of interleukin-2 production Source: UniProtKB
  • positive regulation of JUN kinase activity Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of protein homodimerization activity Source: UniProtKB
  • positive regulation of T cell cytokine production Source: UniProtKB
  • positive regulation of tumor necrosis factor-mediated signaling pathway Source: Ensembl
  • programmed necrotic cell death Source: Ensembl
  • protein autoubiquitination Source: UniProtKB
  • protein catabolic process Source: Ensembl
  • protein-containing complex assembly Source: ProtInc
  • protein deubiquitination Source: Reactome
  • protein heterooligomerization Source: Ensembl
  • protein homotrimerization Source: UniProtKB
  • protein K63-linked ubiquitination Source: UniProtKB
  • regulation of apoptotic process Source: UniProtKB
  • regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Reactome
  • regulation of immunoglobulin secretion Source: Ensembl
  • regulation of tumor necrosis factor-mediated signaling pathway Source: Reactome
  • response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
  • signal transduction Source: ProtInc
  • tumor necrosis factor-mediated signaling pathway Source: UniProtKB

Keywordsi

Molecular functionTransferase
Biological processApoptosis, Ubl conjugation pathway
LigandLipid-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-140534 Ligand-dependent caspase activation
R-HSA-3371378 Regulation by c-FLIP
R-HSA-5213460 RIPK1-mediated regulated necrosis
R-HSA-5218900 CASP8 activity is inhibited
R-HSA-5357786 TNFR1-induced proapoptotic signaling
R-HSA-5357905 Regulation of TNFR1 signaling
R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway
R-HSA-5668541 TNFR2 non-canonical NF-kB pathway
R-HSA-5675482 Regulation of necroptotic cell death
R-HSA-5676594 TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
R-HSA-5689880 Ub-specific processing proteases
R-HSA-69416 Dimerization of procaspase-8
R-HSA-75893 TNF signaling
R-HSA-933541 TRAF6 mediated IRF7 activation
R-HSA-933542 TRAF6 mediated NF-kB activation
SignaLinkiQ12933
SIGNORiQ12933
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
TNF receptor-associated factor 2 (EC:2.3.2.27)
Alternative name(s):
E3 ubiquitin-protein ligase TRAF2
RING-type E3 ubiquitin transferase TRAF2Curated
Tumor necrosis factor type 2 receptor-associated protein 3
Gene namesi
Name:TRAF2
Synonyms:TRAP3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000127191.17
HGNCiHGNC:12032 TRAF2
MIMi601895 gene
neXtProtiNX_Q12933

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi11S → A: Reduces global phosphorylation. Partial reduction of TNF-dependent activation of NF-kappa-B and activation of JNK. 1 Publication1
Mutagenesisi11S → D: Slight increase of TNF-dependent activation of NF-kappa-B and activation of JNK. 1 Publication1
Mutagenesisi31K → R: Abolishes 'Lys-63'-linked polyubiquitination. 1
Mutagenesisi117T → A: Loss of phosphorylation site. Abolishes activation of NF-kappa-B. 1 Publication1
Mutagenesisi285I → A: Strongly reduced interaction with BIRC3. 1 Publication1
Mutagenesisi288V → A: Strongly reduced interaction with BIRC3. 1 Publication1
Mutagenesisi292E → A: Strongly reduced interaction with BIRC3. 1 Publication1

Organism-specific databases

DisGeNETi7186
OpenTargetsiENSG00000127191
PharmGKBiPA164742666

Polymorphism and mutation databases

BioMutaiTRAF2
DMDMi23503103

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000563992 – 501TNF receptor-associated factor 2Add BLAST500

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei5PhosphoserineCombined sources1
Modified residuei7PhosphothreonineCombined sources1
Modified residuei11PhosphoserineCombined sources1 Publication1
Modified residuei22PhosphothreonineCombined sources1
Cross-linki31Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei117Phosphothreonine; by PKC1 Publication1

Post-translational modificationi

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.1 Publication
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.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ12933
MaxQBiQ12933
PaxDbiQ12933
PeptideAtlasiQ12933
PRIDEiQ12933
ProteomicsDBi59035
59036 [Q12933-2]
59037 [Q12933-3]
59038 [Q12933-4]

PTM databases

iPTMnetiQ12933
PhosphoSitePlusiQ12933

Expressioni

Gene expression databases

BgeeiENSG00000127191
CleanExiHS_TRAF2
ExpressionAtlasiQ12933 baseline and differential
GenevisibleiQ12933 HS

Organism-specific databases

HPAiCAB004603
HPA009972
HPA010634

Interactioni

Subunit structurei

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, EDAR and IL15RA (PubMed:8627180, PubMed:9153189, PubMed:9692890, PubMed:9488716, PubMed:9774460, PubMed:9607925, PubMed:9418902, PubMed:10463949, 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 promotes 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).By similarity52 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself7EBI-355744,EBI-355744
B2R8Y43EBI-355744,EBI-10175581
G2XKQ03EBI-355744,EBI-10175576
P889613EBI-355744,EBI-7907665From Human herpesvirus 8 type M.
AASDHPPTQ9NRN76EBI-355744,EBI-740884
AESQ081173EBI-355744,EBI-717810
AFF4Q9UHB73EBI-355744,EBI-395282
AFF4Q9UHB7-23EBI-355744,EBI-10261324
AMOTL2Q9Y2J4-43EBI-355744,EBI-10187270
ANKRD36BP1Q96IX96EBI-355744,EBI-744859
APPL1Q9UKG12EBI-355744,EBI-741243
AQP1P299723EBI-355744,EBI-745213
ARSJQ8N5N63EBI-355744,EBI-10266832
ASCC1Q8N9N23EBI-355744,EBI-10268317
ATXN1P542537EBI-355744,EBI-930964
AXIN1O151693EBI-355744,EBI-710484
BAHD1Q8TBE03EBI-355744,EBI-742750
BANPB4DE543EBI-355744,EBI-16429313
BANPQ8N9N54EBI-355744,EBI-744695
BANPQ8N9N5-73EBI-355744,EBI-16429296
BCL10O959998EBI-355744,EBI-958922
BEX2Q9BXY85EBI-355744,EBI-745073
BIRC2Q1349014EBI-355744,EBI-514538
BIRC3Q134897EBI-355744,EBI-517709
C17orf82Q86X595EBI-355744,EBI-8465536
CAPN15O758084EBI-355744,EBI-6149008
Casp12O087366EBI-355744,EBI-6140033From Mus musculus.
CATSPER1Q8NEC53EBI-355744,EBI-744545
CBX8Q9HC525EBI-355744,EBI-712912
CCDC198Q9NVL85EBI-355744,EBI-10238351
CCHCR1Q8TD31-35EBI-355744,EBI-10175300
CCNJLF6RF563EBI-355744,EBI-10177725
CD40P259429EBI-355744,EBI-525714
CDC20BQ86Y333EBI-355744,EBI-10260504
CDCA3Q996186EBI-355744,EBI-739534
CDKN1BP465275EBI-355744,EBI-519280
CEP57L1Q8IYX8-23EBI-355744,EBI-10181988
CREB5Q02930-35EBI-355744,EBI-10192698
CYB5R2Q6BCY43EBI-355744,EBI-744761
DTNBO609414EBI-355744,EBI-740402
EDARADDQ8WWZ35EBI-355744,EBI-2949647
EFEMP1A0A0S2Z3V13EBI-355744,EBI-16434097
EFEMP1Q1280511EBI-355744,EBI-536772
EFHC1Q5JVL45EBI-355744,EBI-743105
EGFRP005333EBI-355744,EBI-297353
ENKD1Q9H0I26EBI-355744,EBI-744099
ERN1O754603EBI-355744,EBI-371750
ETV6A0A0S2Z3N63EBI-355744,EBI-16434659
EWSR1Q018443EBI-355744,EBI-739737
EXOC3-AS1Q8N2X68EBI-355744,EBI-749333
FAM107AO95990-44EBI-355744,EBI-11977223
FAM120BQ96EK73EBI-355744,EBI-739883
FAM161AQ3B8204EBI-355744,EBI-719941
FAM192AQ9GZU83EBI-355744,EBI-2371956
FAM90A1Q86YD75EBI-355744,EBI-6658203
FBXO28Q9NVF75EBI-355744,EBI-740282
FDXACB1Q9BRP75EBI-355744,EBI-10297077
FNDC3BQ53EP0-33EBI-355744,EBI-10242151
GABPB1Q065476EBI-355744,EBI-618165
GORASP2Q9H8Y86EBI-355744,EBI-739467
GPKOWQ929175EBI-355744,EBI-746309
GSG1Q2KHT43EBI-355744,EBI-10239244
GSTP1P092115EBI-355744,EBI-353467
HENMT1Q5T8I93EBI-355744,EBI-9675710
Hoxa1P090223EBI-355744,EBI-3957603From Mus musculus.
IQUBQ8NA543EBI-355744,EBI-10220600
KIFC3Q9BVG83EBI-355744,EBI-2125614
KLF3P576825EBI-355744,EBI-8472267
LNX1Q8TBB15EBI-355744,EBI-739832
MAP3K1Q132332EBI-355744,EBI-49776
Map3k1Q629252EBI-355744,EBI-636664From Rattus norvegicus.
MAP3K14Q995587EBI-355744,EBI-358011
MAP3K5Q996834EBI-355744,EBI-476263
MAVSQ7Z4343EBI-355744,EBI-995373
METTL13Q8N6R04EBI-355744,EBI-1053295
MISPQ8IVT24EBI-355744,EBI-2555085
MORN3Q6PF185EBI-355744,EBI-9675802
NATD1Q8N6N63EBI-355744,EBI-8656665
NEBLO760415EBI-355744,EBI-2880203
NFIL3Q166493EBI-355744,EBI-3951858
NgfrP071743EBI-355744,EBI-1038810From Rattus norvegicus.
NMUR2Q9GZQ43EBI-355744,EBI-10303844
NRF1Q166563EBI-355744,EBI-2547810
NSP1P890553EBI-355744,EBI-9522973From Rotavirus sp..
NUDT16L1Q9BRJ75EBI-355744,EBI-2949792
PCGF5Q86SE93EBI-355744,EBI-2827999
PGBD1Q96JS36EBI-355744,EBI-10290053
PIN1Q135266EBI-355744,EBI-714158
PPLO604377EBI-355744,EBI-368321
PPP1R18Q6NYC85EBI-355744,EBI-2557469
PRKAB2O437418EBI-355744,EBI-1053424
PRKRIP1Q9H8753EBI-355744,EBI-744488
RAD23AP547256EBI-355744,EBI-746453
RASSF5Q8WWW03EBI-355744,EBI-367390
RBM41Q96IZ55EBI-355744,EBI-740773
RCOR3Q9P2K34EBI-355744,EBI-743428
RFX3P483803EBI-355744,EBI-742557
RIPK1Q135466EBI-355744,EBI-358507
RIPPLY1Q0D2K35EBI-355744,EBI-10226430
RIPPLY3P570554EBI-355744,EBI-12092053
RNF146Q9NTX73EBI-355744,EBI-722397
SH2D4AQ9H7885EBI-355744,EBI-747035
SMG9Q9H0W85EBI-355744,EBI-2872322
SNRNP25Q9BV903EBI-355744,EBI-9675976
SPG21Q9NZD86EBI-355744,EBI-742688
SYT17Q9BSW75EBI-355744,EBI-745392
TANKQ928444EBI-355744,EBI-356349
TAOK3Q9H2K82EBI-355744,EBI-1384100
TBK1Q9UHD24EBI-355744,EBI-356402
TCEA2Q155606EBI-355744,EBI-710310
TEKT3Q9BXF95EBI-355744,EBI-8644516
THAP7Q9BT498EBI-355744,EBI-741350
THOP1Q96CV83EBI-355744,EBI-6137619
TIFAQ96CG37EBI-355744,EBI-740711
TNFAIP3P215805EBI-355744,EBI-527670
TNFRSF12AQ9NP843EBI-355744,EBI-2851995
TNFRSF14Q929564EBI-355760,EBI-1056653
TNFRSF1AP194384EBI-355744,EBI-299451
TNFRSF1BP203333EBI-355744,EBI-358983
TNIKQ9UKE52EBI-355744,EBI-1051794
TRADDQ156288EBI-355744,EBI-359215
TRAF1Q130776EBI-355744,EBI-359224
Traf5P701912EBI-355744,EBI-523899From Mus musculus.
TRAF6Q9Y4K312EBI-355744,EBI-359276
TRIM42Q8IWZ53EBI-355744,EBI-5235829
TROAPQ128153EBI-355744,EBI-2349743
TSHZ3Q63HK53EBI-355744,EBI-9053916
TSSC4Q9Y5U23EBI-355744,EBI-717229
UBXN11Q5T1245EBI-355744,EBI-746004
USF1P224153EBI-355744,EBI-1054489
USP2O756046EBI-355744,EBI-743272
USP53Q70EK83EBI-355744,EBI-742050
VWA2Q5GFL63EBI-355744,EBI-10243723
YES1P079473EBI-355744,EBI-515331
ZBTB16Q055164EBI-355744,EBI-711925
ZBTB25P242784EBI-355744,EBI-739899
ZC2HC1CQ53FD03EBI-355744,EBI-740767
ZFAND6Q6FIF06EBI-355744,EBI-724630
ZMAT2Q96NC05EBI-355744,EBI-2682299
ZNF410Q86VK43EBI-355744,EBI-720304
ZNF410Q86VK4-34EBI-355744,EBI-11741890
ZNF488Q96MN93EBI-355744,EBI-948288
ZNF509Q32MK93EBI-355744,EBI-10239929
ZNF544Q6NX493EBI-355744,EBI-2841978
ZNF572Q7Z3I74EBI-355744,EBI-10172590
ZNF655Q8N7203EBI-355744,EBI-625509
ZNF662Q6ZS27-33EBI-355744,EBI-10255155
ZNF688A0A0S2Z6P03EBI-355744,EBI-16429989
ZSCAN23Q3MJ624EBI-355744,EBI-5667532
ZSCAN32I3L3J23EBI-355744,EBI-10178206

GO - Molecular functioni

  • CD40 receptor binding Source: BHF-UCL
  • enzyme binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • mitogen-activated protein kinase kinase kinase binding Source: Ensembl
  • protein kinase binding Source: ParkinsonsUK-UCL
  • protein phosphatase binding Source: UniProtKB
  • thioesterase binding Source: UniProtKB
  • tumor necrosis factor receptor binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113038, 359 interactors
CORUMiQ12933
DIPiDIP-6223N
ELMiQ12933
IntActiQ12933, 353 interactors
MINTiQ12933
STRINGi9606.ENSP00000247668

Structurei

Secondary structure

1501
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi21 – 23Combined sources3
Helixi25 – 27Combined sources3
Helixi30 – 32Combined sources3
Turni35 – 37Combined sources3
Beta strandi42 – 46Combined sources5
Beta strandi52 – 54Combined sources3
Helixi55 – 61Combined sources7
Helixi62 – 64Combined sources3
Helixi70 – 74Combined sources5
Turni80 – 83Combined sources4
Helixi87 – 89Combined sources3
Helixi94 – 101Combined sources8
Beta strandi103 – 106Combined sources4
Beta strandi115 – 117Combined sources3
Helixi118 – 124Combined sources7
Turni125 – 127Combined sources3
Helixi130 – 133Combined sources4
Helixi315 – 318Combined sources4
Helixi335 – 347Combined sources13
Beta strandi350 – 358Combined sources9
Helixi361 – 369Combined sources9
Beta strandi375 – 377Combined sources3
Beta strandi381 – 384Combined sources4
Beta strandi389 – 395Combined sources7
Helixi400 – 402Combined sources3
Turni403 – 405Combined sources3
Beta strandi406 – 414Combined sources9
Helixi419 – 421Combined sources3
Beta strandi430 – 434Combined sources5
Beta strandi443 – 447Combined sources5
Helixi454 – 456Combined sources3
Beta strandi460 – 463Combined sources4
Beta strandi467 – 474Combined sources8
Helixi476 – 480Combined sources5
Turni482 – 484Combined sources3
Beta strandi490 – 496Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CA4X-ray2.20A/B/C/D/E/F334-501[»]
1CA9X-ray2.30A/B/C/D/E/F310-501[»]
1CZYX-ray2.00A/B/C334-501[»]
1CZZX-ray2.70A/B/C315-501[»]
1D00X-ray2.00A/B/C/D/E/F/G/H334-501[»]
1D01X-ray2.00A/B/C/D/E/F334-501[»]
1D0AX-ray2.00A/B/C/D/E/F334-501[»]
1D0JX-ray2.50A/B/C/D/E/F334-501[»]
1F3VX-ray2.00B331-501[»]
1QSCX-ray2.40A/B/C311-501[»]
3KNVX-ray1.90A1-133[»]
3M06X-ray2.67A/B/C/D/E/F266-329[»]
3M0AX-ray2.61A/B/C266-329[»]
3M0DX-ray2.80A/B266-329[»]
ProteinModelPortaliQ12933
SMRiQ12933
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ12933

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini351 – 496MATHPROSITE-ProRule annotationAdd BLAST146

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni283 – 293Important for interaction with BIRC2 and BIRC3By similarityAdd BLAST11

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili299 – 3481 PublicationAdd BLAST50

Domaini

The coiled coil domain mediates homo- and hetero-oligomerization.1 Publication
The MATH/TRAF domain binds to receptor cytoplasmic domains.1 Publication
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.1 Publication

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri34 – 73RING-typePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri124 – 180TRAF-type 1PROSITE-ProRule annotationAdd BLAST57
Zinc fingeri177 – 233TRAF-type 2PROSITE-ProRule annotationAdd BLAST57

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ISDM Eukaryota
ENOG4111M70 LUCA
GeneTreeiENSGT00550000074359
HOGENOMiHOG000231558
HOVERGENiHBG058222
InParanoidiQ12933
KOiK03173
OMAiSACRNVL
OrthoDBiEOG091G0GHD
PhylomeDBiQ12933
TreeFamiTF321154

Family and domain databases

CDDicd03778 MATH_TRAF2, 1 hit
Gene3Di2.60.210.10, 1 hit
3.30.40.10, 3 hits
InterProiView protein in InterPro
IPR002083 MATH/TRAF_dom
IPR012227 TNF_rcpt--assoc_TRAF
IPR008974 TRAF-like
IPR027133 TRAF2
IPR037305 TRAF2_MATH
IPR032070 TRAF_BIRC3-bd
IPR018957 Znf_C3HC4_RING-type
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
IPR001293 Znf_TRAF
PANTHERiPTHR10131:SF21 PTHR10131:SF21, 1 hit
PfamiView protein in Pfam
PF16673 TRAF_BIRC3_bd, 1 hit
PF00097 zf-C3HC4, 1 hit
PF02176 zf-TRAF, 1 hit
PIRSFiPIRSF015614 TRAF, 1 hit
SMARTiView protein in SMART
SM00061 MATH, 1 hit
SM00184 RING, 1 hit
SUPFAMiSSF49599 SSF49599, 1 hit
PROSITEiView protein in PROSITE
PS50144 MATH, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit
PS50145 ZF_TRAF, 2 hits

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q12933-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAASVTPPG SLELLQPGFS KTLLGTKLEA KYLCSACRNV LRRPFQAQCG
60 70 80 90 100
HRYCSFCLAS ILSSGPQNCA ACVHEGIYEE GISILESSSA FPDNAARREV
110 120 130 140 150
ESLPAVCPSD GCTWKGTLKE YESCHEGRCP LMLTECPACK GLVRLGEKER
160 170 180 190 200
HLEHECPERS LSCRHCRAPC CGADVKAHHE VCPKFPLTCD GCGKKKIPRE
210 220 230 240 250
KFQDHVKTCG KCRVPCRFHA IGCLETVEGE KQQEHEVQWL REHLAMLLSS
260 270 280 290 300
VLEAKPLLGD QSHAGSELLQ RCESLEKKTA TFENIVCVLN REVERVAMTA
310 320 330 340 350
EACSRQHRLD QDKIEALSSK VQQLERSIGL KDLAMADLEQ KVLEMEASTY
360 370 380 390 400
DGVFIWKISD FARKRQEAVA GRIPAIFSPA FYTSRYGYKM CLRIYLNGDG
410 420 430 440 450
TGRGTHLSLF FVVMKGPNDA LLRWPFNQKV TLMLLDQNNR EHVIDAFRPD
460 470 480 490 500
VTSSSFQRPV NDMNIASGCP LFCPVSKMEA KNSYVRDDAI FIKAIVDLTG

L
Length:501
Mass (Da):55,859
Last modified:September 19, 2002 - v2
Checksum:iC508BE185B783B20
GO
Isoform 2 (identifier: Q12933-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     122-122: E → EVKMPACGMVTEAPAVGSRPRSPSSYDLVLHVPLTGAEACLMSVEEETELLLR

Note: No experimental confirmation available.
Show »
Length:553
Mass (Da):61,384
Checksum:iE5000CF242B2F404
GO
Isoform 3 (identifier: Q12933-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     53-63: Missing.

Note: No experimental confirmation available.
Show »
Length:490
Mass (Da):54,671
Checksum:i9CAF6DDAB0DE64DD
GO
Isoform 4 (identifier: Q12933-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     176-200: Missing.

Note: No experimental confirmation available.
Show »
Length:476
Mass (Da):53,055
Checksum:iBB290C92E8D33D79
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti205 – 310Missing in BAB70792 (PubMed:14702039).CuratedAdd BLAST106
Sequence conflicti343 – 365LEMEA…FARKR → RPFQAQCGHRYCSFCLASIL RKL in AAA87706 (PubMed:7639698).CuratedAdd BLAST23

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03968753 – 63Missing in isoform 3. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_007401122E → EVKMPACGMVTEAPAVGSRP RSPSSYDLVLHVPLTGAEAC LMSVEEETELLLR in isoform 2. 1 Publication1
Alternative sequenceiVSP_039688176 – 200Missing in isoform 4. 1 PublicationAdd BLAST25

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U12597 mRNA Translation: AAA87706.1
AK054686 mRNA Translation: BAB70792.1
AK289722 mRNA Translation: BAF82411.1
AK298370 mRNA Translation: BAG60609.1
BX538160 mRNA Translation: CAD98040.1
AY623660 Genomic DNA Translation: AAT27320.1
AL355987 Genomic DNA No translation available.
AL449425 Genomic DNA No translation available.
CH471090 Genomic DNA Translation: EAW88299.1
BC032410 mRNA Translation: AAH32410.1
BC033810 mRNA Translation: AAH33810.1
BC043492 mRNA Translation: AAH43492.1
BC064662 mRNA Translation: AAH64662.1
CCDSiCCDS7013.1 [Q12933-1]
PIRiS56163
RefSeqiNP_066961.2, NM_021138.3 [Q12933-1]
XP_011517276.1, XM_011518974.2 [Q12933-1]
XP_011517277.1, XM_011518975.2 [Q12933-1]
XP_011517278.1, XM_011518976.2 [Q12933-1]
XP_011517279.1, XM_011518977.2 [Q12933-1]
XP_011517280.1, XM_011518978.2 [Q12933-1]
XP_016870584.1, XM_017015095.1 [Q12933-1]
UniGeneiHs.522506

Genome annotation databases

EnsembliENST00000247668; ENSP00000247668; ENSG00000127191 [Q12933-1]
GeneIDi7186
KEGGihsa:7186
UCSCiuc004cjv.4 human [Q12933-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiTRAF2_HUMAN
AccessioniPrimary (citable) accession number: Q12933
Secondary accession number(s): A8K107
, B4DPJ7, Q7Z337, Q96NT2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: September 19, 2002
Last modified: June 20, 2018
This is version 220 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

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