Protein-coding gene in humans
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, RNF117External IDs OMIM : 601895 ; MGI : 101835 ; HomoloGene : 22520 ; GeneCards : TRAF2 ; OMA :TRAF2 - orthologs Wikidata
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]
References
^ a b c GRCh38: Ensembl release 89: ENSG00000127191 – Ensembl , May 2017
^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026942 – Ensembl , May 2017
^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
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^ Yuasa T, Ohno S, Kehrl JH, Kyriakis JM (August 1998). "Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38" . J. Biol. Chem . 273 (35): 22681–92. doi :10.1074/jbc.273.35.22681 . PMID 9712898 .
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^ Hostager BS, Bishop GA (April 2002). "Role of TNF receptor-associated factor 2 in the activation of IgM secretion by CD40 and CD120b" . J. Immunol . 168 (7): 3318–22. doi :10.4049/jimmunol.168.7.3318 . PMID 11907088 .
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^ Tsao DH, McDonagh T, Telliez JB, Hsu S, Malakian K, Xu GY, Lin LL (June 2000). "Solution structure of N-TRADD and characterization of the interaction of N-TRADD and C-TRAF2, a key step in the TNFR1 signaling pathway" . Mol. Cell . 5 (6): 1051–7. doi :10.1016/S1097-2765(00)80270-1 . PMID 10911999 .
^ Lee SY, Lee SY, Choi Y (April 1997). "TRAF-interacting protein (TRIP): a novel component of the tumor necrosis factor receptor (TNFR)- and CD30-TRAF signaling complexes that inhibits TRAF2-mediated NF-kappaB activation" . J. Exp. Med . 185 (7): 1275–85. doi :10.1084/jem.185.7.1275 . PMC 2196258 . PMID 9104814 .
^ Deng L, Wang C, Spencer E, Yang L, Braun A, You J, Slaughter C, Pickart C, Chen ZJ (October 2000). "Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain" . Cell . 103 (2): 351–61. doi :10.1016/S0092-8674(00)00126-4 . PMID 11057907 . S2CID 18154645 .
Further reading
PDB gallery
1ca4 : STRUCTURE OF TNF RECEPTOR ASSOCIATED FACTOR 2 (TRAF2)
1ca9 : STRUCTURE OF TNF RECEPTOR ASSOCIATED FACTOR 2 IN COMPLEX WITH A PEPTIDE FROM TNF-R2
1czy : CRYSTAL STRUCTURE OF THE COMPLEX BETWEEN THE TRAF DOMAIN OF HUMAN TRAF2 AND AN LMP1 BINDING PEPTIDE
1czz : STRUCTURE OF TNF RECEPTOR ASSOCIATED FACTOR 2 IN COMPLEX WITH A 17-RESIDUE CD40 PEPTIDE
1d00 : STRUCTURE OF TNF RECEPTOR ASSOCIATED FACTOR 2 IN COMPLEX WITH A 5-RESIDUE CD40 PEPTIDE
1d01 : STRUCTURE OF TNF RECEPTOR ASSOCIATED FACTOR 2 IN COMPLEX WITH A HUMAN CD30 PEPTIDE
1d0a : STRUCTURE OF TNF RECEPTOR ASSOCIATED FACTOR 2 (TRAF2) IN COMPLEX WITH A HUMAN OX40 PEPTIDE
1d0j : STRUCTURE OF TNF RECEPTOR ASSOCIATED FACTOR 2 IN COMPLEX WITH A M4-1BB PEPTIDE
1f3v : CRYSTAL STRUCTURE OF THE COMPLEX BETWEEN THE N-TERMINAL DOMAIN OF TRADD AND THE TRAF DOMAIN OF TRAF2
1qsc : CRYSTAL STRUCTURE OF THE TRAF DOMAIN OF TRAF2 IN A COMPLEX WITH A PEPTIDE FROM THE CD40 RECEPTOR
Chemokine CSF
Interferon
IFNAR (α/β, I)
Agonists: Albinterferon
Interferon alpha (interferon alfa, IFN-α)
Interferon alfa (IFNA1 , IFNA2 , IFNA4 , IFNA5 , IFNA6 , IFNA7 , IFNA8 , IFNA10 , IFNA13 , IFNA14 , IFNA16 , IFNA17 , IFNA21 )
Interferon alfa 2a
Interferon alfa 2b
Interferon alfa n1
Interferon alfacon-1
Interferon alpha-n3
Interferon beta (IFN-β) (IFNB1 , IFNB3 )
Interferon beta 1a
Interferon beta 1b
Interferon kappa (IFN-ε/κ/τ/ζ, IFNK)
Interferon omega (IFN-ω, IFNW1)
Peginterferon alfa-2a
Peginterferon alfa-2b
IFNGR (γ, II) IFNLR (λ, III)
See IL-28R (IFNLR) here instead.
Interleukin TGFβ TNF Others