TRAF2

TRAF2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3M0D, 1CA4, 1CA9, 1CZY, 1CZZ, 1D00, 1D01, 1D0A, 1D0J, 1F3V, 1QSC, 3KNV, 3M06, 3M0A
Identifiers
Aliases	TRAF2 , MGC:45012, TRAP, TRAP3, TNF receptor associated factor 2, RNF117
External IDs	OMIM: 601895 MGI: 101835 HomoloGene: 22520 GeneCards: TRAF2
Gene location (Human) Chr. Chromosome 9 (human) [1] Band 9q34.3 Start 136,881,912 bp [1] End 136,926,607 bp [1]
Gene location (Mouse) Chr. Chromosome 2 (mouse) [2] Band 2|2 A3 Start 25,407,994 bp [2] End 25,436,952 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in lymph node cerebellar hemisphere ganglionic eminence spleen popliteal artery left lobe of thyroid gland right lobe of thyroid gland right lobe of liver canal of the cervix minor salivary gland Top expressed in thymus spermatocyte crypt of lieberkuhn of small intestine intestinal villus spleen lip duodenum proximal tubule urethra female urethra More reference expression data BioGPS More reference expression data
Gene ontology Molecular function sphingolipid binding lipid binding CD40 receptor binding mitogen-activated protein kinase kinase kinase binding zinc ion binding signal transducer activity metal ion binding ubiquitin-protein transferase activity protein binding identical protein binding thioesterase binding enzyme binding protein phosphatase binding protein kinase binding ubiquitin protein ligase binding transferase activity tumor necrosis factor receptor binding protein-containing complex binding Cellular component TRAF2-GSTP1 complex AIP1-IRE1 complex ubiquitin ligase complex vesicle membrane cell cortex membrane raft CD40 receptor complex cytoplasmic side of plasma membrane IRE1-TRAF2-ASK1 complex nucleoplasm cytoplasm cytosol protein-containing complex Biological process regulation of apoptotic process positive regulation of tumor necrosis factor-mediated signaling pathway positive regulation of JUN kinase activity negative regulation of glial cell apoptotic process regulation of tumor necrosis factor-mediated signaling pathway protein K63-linked ubiquitination positive regulation of DNA-binding transcription factor activity tumor necrosis factor-mediated signaling pathway activation of NF-kappaB-inducing kinase activity positive regulation of protein homodimerization activity response to endoplasmic reticulum stress protein homotrimerization intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress positive regulation of I-kappaB phosphorylation regulation of JNK cascade protein catabolic process positive regulation of NF-kappaB transcription factor activity positive regulation of interleukin-2 production death-inducing signaling complex assembly positive regulation of T cell cytokine production protein ubiquitination positive regulation of I-kappaB kinase/NF-kappaB signaling positive regulation of extrinsic apoptotic signaling pathway cellular response to nitric oxide regulation of extrinsic apoptotic signaling pathway via death domain receptors I-kappaB kinase/NF-kappaB signaling activation of cysteine-type endopeptidase activity involved in apoptotic process signal transduction protein autoubiquitination negative regulation of neuron death programmed necrotic cell death apoptotic process negative regulation of extrinsic apoptotic signaling pathway via death domain receptors protein deubiquitination protein heterooligomerization protein-containing complex assembly Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7186 22030 Ensembl ENSG00000127191 ENSMUSG00000026942 UniProt Q12933 P39429 RefSeq (mRNA) NM_021138 NM_009422 NM_001290413 RefSeq (protein) NP_066961 NP_001277342 NP_033448 Location (UCSC) Chr 9: 136.88 – 136.93 Mb Chr 2: 25.41 – 25.44 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

TNF receptor-associated factor 2 is a protein that in humans is encoded by the TRAF2 gene. ^[5]

Function

The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms complexes with other TRAF proteins. TRAF2 is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-κB. The protein complex formed by TRAF2 and TRAF1 interacts with the IAP family members cIAP1 and cIAP2, and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. cIAP1 can ubiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of only one transcript has been determined. ^[6]

Signaling pathway of TNF-R1. Dashed grey lines represent multiple steps

Interactions

TRAF2 has been shown to interact with:

• ASK1, ^{[7] [8] [9]}
• BCL10, ^[10]
• BIRC2, ^{[10] [11] [12] [13] [14] [15]}
• Baculoviral IAP repeat-containing protein 3, ^{[10] [12] [13] [14]}
• CASP8AP2, ^[16]
• CD134, ^[17]
• CD137, ^{[17] [18]}
• CD27, ^{[19] [20]}
• CD40, ^{[21] [22] [23]}
• CFLAR, ^{[24] [25]}
• CHUK, ^{[26] [27] [28]}
• Caveolin 1, ^{[29] [30]}
• EDARADD, ^[31]
• HIVEP3, ^[32]
• IKK2, ^{[26] [27]}
• Low affinity nerve growth factor receptor, ^[33]
• MAP3K14, ^{[23] [34]}
• MAP3K1, ^{[35] [36]}
• MAP3K7IP2, ^{[27] [37]}
• MAP4K2, ^[38]
• MAP4K5, ^[39]
• RANK, ^{[40] [41] [42] [43]}
• RIPK1, ^{[23] [44] [45] [46]}
• SPHK1, ^[47]
• TANK, ^{[48] [49] [50] [51]}
• TANK-binding kinase 1, ^{[48] [52]}
• TNFAIP3, ^[53]
• TNFRSF13B, ^[54]
• TNFRSF14, ^{[55] [56]}
• TNFRSF1A, ^{[11] [45] [57]}
• TNFRSF1B, ^{[5] [44] [48] [49] [55] [58] [59]}
• TNFSF14, ^[60]
• TRADD, ^{[23] [44] [46] [48] [57] [61] [62]}
• TRAF interacting protein, ^[63]
• TRAF1, ^{[44] [48]} and
• UBE2N. ^[64]

Model organisms

Model organisms have been used in the study of TRAF2 function. A conditional knockout mouse line called Traf2^{tm1a(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute. ^[65] Male and female animals underwent a standardized phenotypic screen ^[66] to determine the effects of deletion. ^{[67] [68] [69] [70]} Additional screens performed: - In-depth immunological phenotyping ^[71]

Traf2 knockout mouse phenotype

Characteristic	Phenotype
All data available at. [66] [71]
Insulin	Normal
Homozygous viability at P14	Abnormal
Recessive lethal study	Abnormal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Epidermal Immune Composition	Normal
Influenza Challenge	Normal

References

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Further reading

• Wajant H, Henkler F, Scheurich P (2001). "The TNF-receptor-associated factor family: scaffold molecules for cytokine receptors, kinases and their regulators". Cell. Signal. 13 (6): 389–400. doi:10.1016/S0898-6568(01)00160-7. PMID   11384837.
• Bradley JR, Pober JS (2001). "Tumor necrosis factor receptor-associated factors (TRAFs)". Oncogene. 20 (44): 6482–91. doi: 10.1038/sj.onc.1204788 . PMID   11607847.