ID TRAF2_HUMAN Reviewed; 501 AA. AC Q12933; A8K107; B4DPJ7; Q7Z337; Q96NT2; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 19-SEP-2002, sequence version 2. DT 27-MAR-2024, entry version 256. DE RecName: Full=TNF receptor-associated factor 2; DE EC=2.3.2.27; DE AltName: Full=E3 ubiquitin-protein ligase TRAF2; DE AltName: Full=RING-type E3 ubiquitin transferase TRAF2 {ECO:0000305}; DE AltName: Full=Tumor necrosis factor type 2 receptor-associated protein 3; GN Name=TRAF2; Synonyms=TRAP3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH RP TNFRSF1B/TNFR2. RX PubMed=7639698; DOI=10.1042/bj3090825; RA Song H.Y., Donner D.B.; RT "Association of a RING finger protein with the cytoplasmic domain of the RT human type-2 tumour necrosis factor receptor."; RL Biochem. J. 309:825-829(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Brain, Cerebellum, and Kidney; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Endometrium; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG SeattleSNPs variation discovery resource; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon, Fetal brain, Kidney, Leukocyte, Stomach, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 201-501, AND INTERACTION WITH TRAF1 AND RP TNFRSF1B. RX PubMed=8069916; DOI=10.1016/0092-8674(94)90532-0; RA Rothe M., Wong S.C., Henzel W.J., Goeddel D.V.; RT "A novel family of putative signal transducers associated with the RT cytoplasmic domain of the 75 kDa tumor necrosis factor receptor."; RL Cell 78:681-692(1994). RN [9] RP INTERACTION WITH TNFRSF8. RX PubMed=8627180; DOI=10.1084/jem.183.2.669; RA Lee S.Y., Park C.G., Choi Y.; RT "T cell receptor-dependent cell death of T cell hybridomas mediated by the RT CD30 cytoplasmic domain in association with tumor necrosis factor receptor- RT associated factors."; RL J. Exp. Med. 183:669-674(1996). RN [10] RP INTERACTION WITH TANK. RX PubMed=8710854; DOI=10.1073/pnas.93.16.8241; RA Rothe M., Xiong J., Shu H.-B., Williamson K., Goddard A., Goeddel D.V.; RT "I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated RT signal transduction."; RL Proc. Natl. Acad. Sci. U.S.A. 93:8241-8246(1996). RN [11] RP INTERACTION WITH TNFRSF14. RX PubMed=9153189; DOI=10.1074/jbc.272.21.13471; RA Hsu H., Solovyev I., Colombero A., Elliott R., Kelley M., Boyle W.J.; RT "ATAR, a novel tumor necrosis factor receptor family member, signals RT through TRAF2 and TRAF5."; RL J. Biol. Chem. 272:13471-13474(1997). RN [12] RP IDENTIFICATION IN A COMPLEX WITH TNFRSF8; TNFRSF1B, TRAF1 AND TRAIP, AND RP INTERACTION WITH TRAIP. RX PubMed=9104814; DOI=10.1084/jem.185.7.1275; RA Lee S.Y., Lee S.Y., Choi Y.; RT "TRAF-interacting protein (TRIP): a novel component of the tumor necrosis RT factor receptor (TNFR)- and CD30-TRAF signaling complexes that inhibits RT TRAF2-mediated NF-kappaB activation."; RL J. Exp. Med. 185:1275-1285(1997). RN [13] RP INTERACTION WITH MAP3K14. RX PubMed=9020361; DOI=10.1038/385540a0; RA Malinin N.L., Boldin M.P., Kovalenko A.V., Wallach D.; RT "MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL- RT 1."; RL Nature 385:540-544(1997). RN [14] RP INTERACTION WITH TNFRSF5. RX PubMed=9718306; DOI=10.1021/bi981067q; RA Pullen S.S., Miller H.G., Everdeen D.S., Dang T.T., Crute J.J., Kehry M.R.; RT "CD40-tumor necrosis factor receptor-associated factor (TRAF) interactions: RT regulation of CD40 signaling through multiple TRAF binding sites and TRAF RT hetero-oligomerization."; RL Biochemistry 37:11836-11845(1998). RN [15] RP INTERACTION WITH RIPK2. RX PubMed=9705938; DOI=10.1016/s0960-9822(07)00352-1; RA Thome M., Hofmann K., Burns K., Martinon F., Bodmer J.-L., Mattmann C., RA Tschopp J.; RT "Identification of CARDIAK, a RIP-like kinase that associates with caspase- RT 1."; RL Curr. Biol. 8:885-888(1998). RN [16] RP INTERACTION WITH CD27. RX PubMed=9692890; RX DOI=10.1002/(sici)1521-4141(199807)28:07<2208::aid-immu2208>3.0.co;2-l; RA Gravestein L.A., Amsen D., Boes M., Calvo C.R., Kruisbeek A.M., Borst J.; RT "The TNF receptor family member CD27 signals to Jun N-terminal kinase via RT Traf-2."; RL Eur. J. Immunol. 28:2208-2216(1998). RN [17] RP INTERACTION WITH TNFRSF4. RX PubMed=9488716; DOI=10.1074/jbc.273.10.5808; RA Kawamata S., Hori T., Imura A., Takaori-Kondo A., Uchiyama T.; RT "Activation of OX40 signal transduction pathways leads to tumor necrosis RT factor receptor-associated factor (TRAF) 2- and TRAF5-mediated NF-kappaB RT activation."; RL J. Biol. Chem. 273:5808-5814(1998). RN [18] RP INTERACTION WITH TNFRSF11A. RX PubMed=9774460; DOI=10.1074/jbc.273.43.28355; RA Wong B.R., Josien R., Lee S.Y., Vologodskaia M., Steinman R.M., Choi Y.; RT "The TRAF family of signal transducers mediates NF-kappaB activation by the RT TRANCE receptor."; RL J. Biol. Chem. 273:28355-28359(1998). RN [19] RP INTERACTION WITH CDK9. RX PubMed=9827693; RX DOI=10.1002/(sici)1097-4644(19981215)71:4<467::aid-jcb2>3.3.co;2-7; RA MacLachlan T.K., Sang N., De Luca A., Puri P.L., Levrero M., Giordano A.; RT "Binding of CDK9 to TRAF2."; RL J. Cell. Biochem. 71:467-478(1998). RN [20] RP INTERACTION WITH TNFRSF9. RX PubMed=9607925; DOI=10.1084/jem.187.11.1849; RA Saoulli K., Lee S.Y., Cannons J.L., Yeh W.C., Santana A., Goldstein M.D., RA Bangia N., DeBenedette M.A., Mak T.W., Choi Y., Watts T.H.; RT "CD28-independent, TRAF2-dependent costimulation of resting T cells by 4- RT 1BB ligand."; RL J. Exp. Med. 187:1849-1862(1998). RN [21] RP INTERACTION WITH MAP3K5. RX PubMed=9774977; DOI=10.1016/s1097-2765(00)80283-x; RA Nishitoh H., Saitoh M., Mochida Y., Takeda K., Nakano H., Rothe M., RA Miyazono K., Ichijo H.; RT "ASK1 is essential for JNK/SAPK activation by TRAF2."; RL Mol. Cell 2:389-395(1998). RN [22] RP INTERACTION WITH TNFRSF4 AND TNFRSF9. RX PubMed=9418902; DOI=10.1128/mcb.18.1.558; RA Arch R.H., Thompson C.B.; RT "4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth RT factor receptor subfamily that bind TNF receptor-associated factors and RT activate nuclear factor kappaB."; RL Mol. Cell. Biol. 18:558-565(1998). RN [23] RP IDENTIFICATION IN A COMPLEX WITH TBK1 AND TANK. RC TISSUE=Spleen; RX PubMed=10581243; DOI=10.1093/emboj/18.23.6694; RA Pomerantz J.L., Baltimore D.; RT "NF-kB activation by a signaling complex containing TRAF2, TANK, and TBK1, RT a novel IKK-related kinase."; RL EMBO J. 18:6694-6704(1999). RN [24] RP RETRACTED PAPER. RX PubMed=10463949; DOI=10.1096/fasebj.13.12.1575; RA Bulfone-Paus S., Bulanova E., Pohl T., Budagian V., Duerkop H., RA Rueckert R., Kunzendorf U., Paus R., Krause H.; RT "Death deflected: IL-15 inhibits TNF-alpha-mediated apoptosis in RT fibroblasts by TRAF2 recruitment to the IL-15Ralpha chain."; RL FASEB J. 13:1575-1585(1999). RN [25] RP RETRACTION NOTICE OF PUBMED:10463949. RX PubMed=21357251; DOI=10.1096/fj.11-0309ret; RA Bulfone-Paus S., Bulanova E., Pohl T., Budagian V., Duerkop H., RA Rueckert R., Kunzendorf U., Paus R., Krause H.; RL FASEB J. 25:1118-1118(2011). RN [26] RP INTERACTION WITH MAP3K1, AND FUNCTION. RX PubMed=10346818; DOI=10.1101/gad.13.10.1297; RA Baud V., Liu Z.-G., Bennett B., Suzuki N., Xia Y., Karin M.; RT "Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 RT is sufficient for JNK and IKK activation and target gene induction via an RT amino-terminal effector domain."; RL Genes Dev. 13:1297-1308(1999). RN [27] RP INTERACTION WITH TNFRSF18. RC TISSUE=T-cell; RX PubMed=10037686; DOI=10.1074/jbc.274.10.6056; RA Kwon B., Yu K.-Y., Ni J., Yu G.-L., Jang I.-K., Kim Y.-J., Xing L., Liu D., RA Wang S.-X., Kwon B.S.; RT "Identification of a novel activation-inducible protein of the tumor RT necrosis factor receptor superfamily and its ligand."; RL J. Biol. Chem. 274:6056-6061(1999). RN [28] RP INTERACTION WITH TNFRSF16. RX PubMed=10514511; DOI=10.1074/jbc.274.42.30202; RA Ye X., Mehlen P., Rabizadeh S., VanArsdale T., Zhang H., Shin H., RA Wang J.J.L., Leo E., Zapata J.M., Hauser C.A., Reed J.C., Bredesen D.E.; RT "TRAF family proteins interact with the common neurotrophin receptor and RT modulate apoptosis induction."; RL J. Biol. Chem. 274:30202-30208(1999). RN [29] RP INTERACTION WITH TNIK. RX PubMed=10521462; DOI=10.1074/jbc.274.43.30729; RA Fu C.A., Shen M., Huang B.C., Lasaga J., Payan D.G., Luo Y.; RT "TNIK, a novel member of the germinal center kinase family that activates RT the c-Jun N-terminal kinase pathway and regulates the cytoskeleton."; RL J. Biol. Chem. 274:30729-30737(1999). RN [30] RP INTERACTION WITH TNFRSF19. RX PubMed=10809768; DOI=10.1074/jbc.275.20.15336; RA Eby M.T., Jasmin A., Kumar A., Sharma K., Chaudhary P.M.; RT "TAJ, a novel member of the tumor necrosis factor receptor family, RT activates the c-Jun N-terminal kinase pathway and mediates caspase- RT independent cell death."; RL J. Biol. Chem. 275:15336-15342(2000). RN [31] RP INTERACTION WITH TDP2. RX PubMed=10764746; DOI=10.1074/jbc.m000531200; RA Pype S., Declercq W., Ibrahimi A., Michiels C., Van Rietschoten J.G.I., RA Dewulf N., de Boer M., Vandenabeele P., Huylebroeck D., Remacle J.E.; RT "TTRAP, a novel protein that associates with CD40, tumor necrosis factor RT (TNF) receptor-75 and TNF receptor-associated factors (TRAFs), and that RT inhibits nuclear factor-kappa B activation."; RL J. Biol. Chem. 275:18586-18593(2000). RN [32] RP INTERACTION WITH TNFRSF13B. RX PubMed=10880535; DOI=10.1084/jem.192.1.137; RA Xia X.-Z., Treanor J., Senaldi G., Khare S.D., Boone T., Kelley M., RA Theill L.E., Colombero A., Solovyev I., Lee F., McCabe S., Elliott R., RA Miner K., Hawkins N., Guo J., Stolina M., Yu G., Wang J., Delaney J., RA Meng S.-Y., Boyle W.J., Hsu H.; RT "TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor RT family member involved in B cell regulation."; RL J. Exp. Med. 192:137-143(2000). RN [33] RP INTERACTION WITH EDAR. RX PubMed=11035039; DOI=10.1074/jbc.m008356200; RA Kumar A., Eby M.T., Sinha S., Jasmin A., Chaudhary P.M.; RT "The ectodermal dysplasia receptor activates the nuclear factor-kappaB, RT JNK, and cell death pathways and binds to ectodysplasin A."; RL J. Biol. Chem. 276:2668-2677(2001). RN [34] RP INTERACTION WITH ERN1 AND TAOK3. RX PubMed=11278723; DOI=10.1074/jbc.m010677200; RA Yoneda T., Imaizumi K., Oono K., Yui D., Gomi F., Katayama T., Tohyama M.; RT "Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, RT through tumor necrosis factor receptor-associated factor 2-dependent RT mechanism in response to the ER stress."; RL J. Biol. Chem. 276:13935-13940(2001). RN [35] RP INTERACTION WITH SIAH2, AND DEGRADATION. RX PubMed=12411493; DOI=10.1093/emboj/cdf576; RA Habelhah H., Frew I.J., Laine A., Janes P.W., Relaix F., Sassoon D., RA Bowtell D.D.L., Ronai Z.; RT "Stress-induced decrease in TRAF2 stability is mediated by Siah2."; RL EMBO J. 21:5756-5765(2002). RN [36] RP FUNCTION. RX PubMed=11784851; DOI=10.1128/mcb.22.3.737-749.2002; RA Chadee D.N., Yuasa T., Kyriakis J.M.; RT "Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 RT by the Ste20p homologue GCK and the adapter protein TRAF2."; RL Mol. Cell. Biol. 22:737-749(2002). RN [37] RP FUNCTION, INTERACTION WITH BIRC2 AND BIRC3, UBIQUITINATION BY BIRC2, AND RP DEGRADATION. RX PubMed=11907583; DOI=10.1038/416345a; RA Li X., Yang Y., Ashwell J.D.; RT "TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2."; RL Nature 416:345-347(2002). RN [38] RP FUNCTION, UBIQUITINATION, AND DEUBIQUITINATION BY CYLD. RX PubMed=12917689; DOI=10.1038/nature01803; RA Trompouki E., Hatzivassiliou E., Tsichritzis T., Farmer H., Ashworth A., RA Mosialos G.; RT "CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB RT activation by TNFR family members."; RL Nature 424:793-796(2003). RN [39] RP INTERACTION WITH CYLD, UBIQUITINATION, AND DEUBIQUITINATION BY CYLD. RX PubMed=12917691; DOI=10.1038/nature01802; RA Kovalenko A., Chable-Bessia C., Cantarella G., Israeel A., Wallach D., RA Courtois G.; RT "The tumour suppressor CYLD negatively regulates NF-kappaB signalling by RT deubiquitination."; RL Nature 424:801-805(2003). RN [40] RP INTERACTION WITH DAB2IP. RX PubMed=15310755; DOI=10.1074/jbc.m407617200; RA Zhang H., Zhang R., Luo Y., D'Alessio A., Pober J.S., Min W.; RT "AIP1/DAB2IP, a novel member of the Ras-GAP family, transduces TRAF2- RT induced ASK1-JNK activation."; RL J. Biol. Chem. 279:44955-44965(2004). RN [41] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TRAF3, AND SUBUNIT. RX PubMed=15383523; DOI=10.1074/jbc.m407284200; RA He L., Grammer A.C., Wu X., Lipsky P.E.; RT "TRAF3 forms heterotrimers with TRAF2 and modulates its ability to mediate RT NF-{kappa}B activation."; RL J. Biol. Chem. 279:55855-55865(2004). RN [42] RP FUNCTION, AND INTERACTION WITH EIF2AK2. RX PubMed=15121867; DOI=10.1128/mcb.24.10.4502-4512.2004; RA Gil J., Garcia M.A., Gomez-Puertas P., Guerra S., Rullas J., Nakano H., RA Alcami J., Esteban M.; RT "TRAF family proteins link PKR with NF-kappa B activation."; RL Mol. Cell. Biol. 24:4502-4512(2004). RN [43] RP INTERACTION WITH MAVS. RX PubMed=16153868; DOI=10.1016/j.molcel.2005.08.014; RA Xu L.-G., Wang Y.-Y., Han K.-J., Li L.-Y., Zhai Z., Shu H.-B.; RT "VISA is an adapter protein required for virus-triggered IFN-beta RT Signaling."; RL Mol. Cell 19:727-740(2005). RN [44] RP UBIQUITINATION, AND DEUBIQUITINATION BY CYLD. RX PubMed=15870263; DOI=10.1128/mcb.25.10.3886-3895.2005; RA Reiley W., Zhang M., Wu X., Granger E., Sun S.C.; RT "Regulation of the deubiquitinating enzyme CYLD by IkappaB kinase gamma- RT dependent phosphorylation."; RL Mol. Cell. Biol. 25:3886-3895(2005). RN [45] RP INTERACTION WITH PTPN2. RX PubMed=15696169; DOI=10.1038/ni1169; RA van Vliet C., Bukczynska P.E., Puryer M.A., Sadek C.M., Shields B.J., RA Tremblay M.L., Tiganis T.; RT "Selective regulation of tumor necrosis factor-induced Erk signaling by Src RT family kinases and the T cell protein tyrosine phosphatase."; RL Nat. Immunol. 6:253-260(2005). RN [46] RP INTERACTION WITH USP48. RX PubMed=16214042; DOI=10.1016/j.cellsig.2005.03.017; RA Tzimas C., Michailidou G., Arsenakis M., Kieff E., Mosialos G., RA Hatzivassiliou E.G.; RT "Human ubiquitin specific protease 31 is a deubiquitinating enzyme RT implicated in activation of nuclear factor-kappaB."; RL Cell. Signal. 18:83-92(2006). RN [47] RP INTERACTION WITH DAB2IP. RX PubMed=17389591; DOI=10.1074/jbc.m701148200; RA Zhang H., Zhang H., Lin Y., Li J., Pober J.S., Min W.; RT "RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site is critical RT for tumor necrosis factor-induced ASK1-JNK/p38 activation."; RL J. Biol. Chem. 282:14788-14796(2007). RN [48] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [49] RP FUNCTION, AND INTERACTION WITH BIRC2. RX PubMed=19506082; DOI=10.1074/jbc.m109.029983; RA Csomos R.A., Brady G.F., Duckett C.S.; RT "Enhanced cytoprotective effects of the inhibitor of apoptosis protein RT cellular IAP1 through stabilization with TRAF2."; RL J. Biol. Chem. 284:20531-20539(2009). RN [50] RP FUNCTION, INTERACTION WITH IKKA; IKKB; TAB2 AND TAB3, UBIQUITINATION AT RP LYS-31, PHOSPHORYLATION AT THR-117, MUTAGENESIS OF THR-117, UBIQUITINATION, RP AND SUBCELLULAR LOCATION. RX PubMed=19150425; DOI=10.1016/j.molcel.2008.11.023; RA Li S., Wang L., Dorf M.E.; RT "PKC phosphorylation of TRAF2 mediates IKKalpha/beta recruitment and K63- RT linked polyubiquitination."; RL Mol. Cell 33:30-42(2009). RN [51] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH TNFRSF1A; RIPK1 AND IKKB, RP MUTAGENESIS OF SER-11, AND PHOSPHORYLATION AT SER-11. RX PubMed=18981220; DOI=10.1128/mcb.00699-08; RA Blackwell K., Zhang L., Thomas G.S., Sun S., Nakano H., Habelhah H.; RT "TRAF2 phosphorylation modulates tumor necrosis factor alpha-induced gene RT expression and cell resistance to apoptosis."; RL Mol. Cell. Biol. 29:303-314(2009). RN [52] RP INTERACTION WITH RELL2. RX PubMed=19969290; DOI=10.1016/j.cellimm.2009.10.013; RA Cusick J.K., Mustian A., Goldberg K., Reyland M.E.; RT "RELT induces cellular death in HEK 293 epithelial cells."; RL Cell. Immunol. 261:1-8(2010). RN [53] RP FUNCTION, AND INTERACTION WITH MAP3K11. RX PubMed=19918265; DOI=10.1038/cr.2009.125; RA Sondarva G., Kundu C.N., Mehrotra S., Mishra R., Rangasamy V., RA Sathyanarayana P., Ray R.S., Rana B., Rana A.; RT "TRAF2-MLK3 interaction is essential for TNF-alpha-induced MLK3 RT activation."; RL Cell Res. 20:89-98(2010). RN [54] RP INTERACTION WITH BIRC2, SUBUNIT, AND HOMOTRIMERIZATION. RX PubMed=20447407; DOI=10.1016/j.jmb.2010.04.055; RA Mace P.D., Smits C., Vaux D.L., Silke J., Day C.L.; RT "Asymmetric recruitment of cIAPs by TRAF2."; RL J. Mol. Biol. 400:8-15(2010). RN [55] RP FUNCTION, AND DOMAIN. RX PubMed=20064526; DOI=10.1016/j.jmb.2010.01.008; RA Zhang L., Blackwell K., Shi Z., Habelhah H.; RT "The RING domain of TRAF2 plays an essential role in the inhibition of RT TNFalpha-induced cell death but not in the activation of NF-kappaB."; RL J. Mol. Biol. 396:528-539(2010). RN [56] RP UBIQUITINATION, AND FUNCTION. RX PubMed=19937093; DOI=10.1007/s11010-009-0315-y; RA Li S., Lu K., Wang J., An L., Yang G., Chen H., Cui Y., Yin X., Xie P., RA Xing G., He F., Zhang L.; RT "Ubiquitin ligase Smurf1 targets TRAF family proteins for ubiquitination RT and degradation."; RL Mol. Cell. Biochem. 338:11-17(2010). RN [57] RP INTERACTION WITH TICAM1, AND FUNCTION. RX PubMed=20047764; DOI=10.1016/j.molimm.2009.12.002; RA Sasai M., Tatematsu M., Oshiumi H., Funami K., Matsumoto M., Hatakeyama S., RA Seya T.; RT "Direct binding of TRAF2 and TRAF6 to TICAM-1/TRIF adaptor participates in RT activation of the Toll-like receptor 3/4 pathway."; RL Mol. Immunol. 47:1283-1291(2010). RN [58] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, UBIQUITINATION, RP INTERACTION WITH SPHK1, AND SPHINGOLIPID BINDING. RX PubMed=20577214; DOI=10.1038/nature09128; RA Alvarez S.E., Harikumar K.B., Hait N.C., Allegood J., Strub G.M., Kim E.Y., RA Maceyka M., Jiang H., Luo C., Kordula T., Milstien S., Spiegel S.; RT "Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase RT TRAF2."; RL Nature 465:1084-1088(2010). RN [59] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [60] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [61] RP IDENTIFICATION IN APOPTOTIC COMPLEX I, AND INTERACTION WITH UXT. RX PubMed=21307340; DOI=10.1091/mbc.e10-10-0827; RA Huang Y., Chen L., Zhou Y., Liu H., Yang J., Liu Z., Wang C.; RT "UXT-V1 protects cells against TNF-induced apoptosis through modulating RT complex II formation."; RL Mol. Biol. Cell 22:1389-1397(2011). RN [62] RP INTERACTION WITH CARD14. RX PubMed=21302310; DOI=10.1002/jcp.22667; RA Scudiero I., Zotti T., Ferravante A., Vessichelli M., Vito P., Stilo R.; RT "Alternative splicing of CARMA2/CARD14 transcripts generates protein RT variants with differential effect on NF-kappaB activation and endoplasmic RT reticulum stress-induced cell death."; RL J. Cell. Physiol. 226:3121-3131(2011). RN [63] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT THR-7; SER-11 AND THR-22, CLEAVAGE OF INITIATOR METHIONINE RP [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [64] RP FUNCTION, AND UBIQUITINATION BY FBXO7. RX PubMed=22212761; DOI=10.1111/j.1582-4934.2012.01524.x; RA Kuiken H.J., Egan D.A., Laman H., Bernards R., Beijersbergen R.L., RA Dirac A.M.; RT "Identification of F-box only protein 7 as a negative regulator of NF- RT kappaB signalling."; RL J. Cell. Mol. Med. 16:2140-2149(2012). RN [65] RP INTERACTION WITH MAP3K5. RX PubMed=22095282; DOI=10.1038/cdd.2011.168; RA Cho J.H., Lee M.K., Yoon K.W., Lee J., Cho S.G., Choi E.J.; RT "Arginine methylation-dependent regulation of ASK1 signaling by PRMT1."; RL Cell Death Differ. 19:859-870(2012). RN [66] RP FUNCTION IN IKBKE UBIQUITINATION. RX PubMed=23453969; DOI=10.1016/j.celrep.2013.01.031; RA Zhou A.Y., Shen R.R., Kim E., Lock Y.J., Xu M., Chen Z.J., Hahn W.C.; RT "IKKepsilon-mediated tumorigenesis requires K63-linked polyubiquitination RT by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex."; RL Cell Rep. 3:724-733(2013). RN [67] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5; THR-7 AND SER-11, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [68] RP INTERACTION WITH GAPDH. RX PubMed=23332158; DOI=10.1016/j.chom.2012.11.010; RA Gao X., Wang X., Pham T.H., Feuerbacher L.A., Lubos M.L., Huang M., RA Olsen R., Mushegian A., Slawson C., Hardwidge P.R.; RT "NleB, a bacterial effector with glycosyltransferase activity, targets RT GAPDH function to inhibit NF-kappaB activation."; RL Cell Host Microbe 13:87-99(2013). RN [69] RP UBIQUITINATION, AND INTERACTION WITH LRRC19. RX PubMed=25026888; DOI=10.1038/ncomms5434; RA Su X., Min S., Cao S., Yan H., Zhao Y., Li H., Chai L., Mei S., Yang J., RA Zhang Y., Zhang Z., Liu F., Sun W., Che Y., Yang R.; RT "LRRC19 expressed in the kidney induces TRAF2/6-mediated signals to prevent RT infection by uropathogenic bacteria."; RL Nat. Commun. 5:4434-4434(2014). RN [70] RP INTERACTION WITH XPNPEP3. RX PubMed=25609706; DOI=10.1242/jcs.149385; RA Inoue M., Kamada H., Abe Y., Higashisaka K., Nagano K., Mukai Y., RA Yoshioka Y., Tsutsumi Y., Tsunoda S.; RT "Aminopeptidase P3, a new member of the TNF-TNFR2 signaling complex, RT induces phosphorylation of JNK1 and JNK2."; RL J. Cell Sci. 128:656-669(2015). RN [71] RP INTERACTION WITH RIPK3. RX PubMed=29883609; DOI=10.1016/j.molcel.2018.05.016; RA Choi S.W., Park H.H., Kim S., Chung J.M., Noh H.J., Kim S.K., Song H.K., RA Lee C.W., Morgan M.J., Kang H.C., Kim Y.S.; RT "PELI1 selectively targets kinase-active RIP3 for ubiquitylation-dependent RT proteasomal degradation."; RL Mol. Cell 70:920-935(2018). RN [72] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 310-501 IN COMPLEX WITH TNFRSF1B. RX PubMed=10206649; DOI=10.1038/19110; RA Park Y.C., Burkitt V., Villa A.R., Tong L., Wu H.; RT "Structural basis for self-association and receptor recognition of human RT TRAF2."; RL Nature 398:533-538(1999). RN [73] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 334-501 IN COMPLEX WITH EBV BNFL1, RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 315-501 IN COMPLEX WITH TNFRSF5, RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 334-501 IN COMPLEX WITH TNFRSF4, RP AND X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 334-501 IN COMPLEX WITH RP TNFRSF9. RX PubMed=10411888; DOI=10.1073/pnas.96.15.8408; RA McWhirter S.M., Pullen S.S., Holton J.M., Crute J.J., Kehry M.R., Alber T.; RT "Crystallographic analysis of CD40 recognition and signaling by human RT TRAF2."; RL Proc. Natl. Acad. Sci. U.S.A. 96:8408-8413(1999). RN [74] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 331-501 IN COMPLEX WITH TRADD. RX PubMed=10892748; DOI=10.1016/s0092-8674(00)80889-2; RA Park Y.C., Ye H., Hsia C., Segal D., Rich R.L., Liou H.C., Myszka D.G., RA Wu H.; RT "A novel mechanism of TRAF signaling revealed by structural and functional RT analyses of the TRADD-TRAF2 interaction."; RL Cell 101:777-787(2000). RN [75] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-133, FUNCTION, AND SUBUNIT. RX PubMed=19810754; DOI=10.1021/bi901462e; RA Yin Q., Lamothe B., Darnay B.G., Wu H.; RT "Structural basis for the lack of E2 interaction in the RING domain of RT TRAF2."; RL Biochemistry 48:10558-10567(2009). RN [76] RP X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 266-330 IN COMPLEXES WITH TRAF1 RP AND BIRC3, FUNCTION, SUBUNIT, COILED-COIL DOMAIN, AND MUTAGENESIS OF RP ILE-285; VAL-288 AND GLU-292. RX PubMed=20385093; DOI=10.1016/j.molcel.2010.03.009; RA Zheng C., Kabaleeswaran V., Wang Y., Cheng G., Wu H.; RT "Crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 RT complexes: affinity, specificity, and regulation."; RL Mol. Cell 38:101-113(2010). CC -!- FUNCTION: Regulates activation of NF-kappa-B and JNK and plays a CC central role in the regulation of cell survival and apoptosis CC (PubMed:22212761). Required for normal antibody isotype switching from CC IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys- CC 63'-linked ubiquitination of target proteins, such as BIRC3, RIPK1 and CC TICAM1. Is an essential constituent of several E3 ubiquitin-protein CC ligase complexes, where it promotes the ubiquitination of target CC proteins by bringing them into contact with other E3 ubiquitin ligases. CC Regulates BIRC2 and BIRC3 protein levels by inhibiting their CC autoubiquitination and subsequent degradation; this does not depend on CC the TRAF2 RING-type zinc finger domain. Plays a role in mediating CC activation of NF-kappa-B by EIF2AK2/PKR. In complex with BIRC2 or CC BIRC3, promotes ubiquitination of IKBKE. {ECO:0000269|PubMed:10346818, CC ECO:0000269|PubMed:11784851, ECO:0000269|PubMed:11907583, CC ECO:0000269|PubMed:12917689, ECO:0000269|PubMed:15121867, CC ECO:0000269|PubMed:15383523, ECO:0000269|PubMed:18981220, CC ECO:0000269|PubMed:19150425, ECO:0000269|PubMed:19506082, CC ECO:0000269|PubMed:19810754, ECO:0000269|PubMed:19918265, CC ECO:0000269|PubMed:19937093, ECO:0000269|PubMed:20047764, CC ECO:0000269|PubMed:20064526, ECO:0000269|PubMed:20385093, CC ECO:0000269|PubMed:20577214, ECO:0000269|PubMed:22212761, CC ECO:0000269|PubMed:23453969}. CC -!- CATALYTIC ACTIVITY: CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; CC EC=2.3.2.27; CC -!- ACTIVITY REGULATION: Has very low E3 ubiquitin ligase activity in the CC absence of sphingosine-1-phosphate. E3 ubiquitin ligase activity is CC strongly activated by cytoplasmic sphingosine-1-phosphate. CC {ECO:0000269|PubMed:20577214}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Homotrimer (PubMed:8069916). Heterotrimer with TRAF1 CC (PubMed:8069916). Heterotrimer with TRAF3 (via TRAF domain) CC (PubMed:15383523, PubMed:20447407). The domain containing the RING-type CC and the first TRAF-type zinc finger can also form homodimers (in vitro) CC (PubMed:19810754). Interacts with TNFRSF1B/TNFR2 (PubMed:7639698, CC PubMed:8069916, PubMed:10206649). Interacts with TNFRSF5/CD40 CC (PubMed:9718306). Interacts with TNFRSF4, TNFRSF7/CD27, TNFRSF8/CD30, CC TNFRSF9/CD137, TNFRSF11A/RANK, TNFRSF13B/TACI, TNFRSF14, TNFRSF16/NGFR, CC TNFRSF17/BCMA, TNFRSF18/AITR, TNFRSF19/TROY, TNFRSF19L/RELT and EDAR CC (PubMed:8627180, PubMed:9153189, PubMed:9692890, PubMed:9488716, CC PubMed:9774460, PubMed:9607925, PubMed:9418902, PubMed:10037686, CC PubMed:10514511, PubMed:10809768, PubMed:10880535, PubMed:11035039, CC PubMed:10411888). Stimulation of TNF-alpha receptor TNFRSF1A leads to CC the formation of two distinct signaling complexes. Plasma membrane- CC bound complex I is composed of TNFRSF1A, TRADD, RIPK1, TRAF2 and CC BIRC2/c-IAP1 or BIRC3 which interacts with CHUCK/IKK-alpha, IKBKB/IKK- CC beta and IKBKG/IKK-gamma promoting cell survival (PubMed:21307340, CC PubMed:18981220). Subsequently, TRADD, RIPK1 and TRAF2 dissociate from CC TNFRSF1A and form cytoplasmic complex II with FADD and caspase CASP8 CC promoting cell apoptosis (PubMed:21307340). Interacts with TRADD CC (PubMed:10892748). Identified in a complex with TNFRSF1A, RIPK1 and CC IKBKB/IKK-beta (PubMed:18981220). Interacts with RIPK2 CC (PubMed:9705938). Interacts with BIRC2 and BIRC3 N-terminus; a single CC BIRC2 or BIRC3 molecule interacts with a heterotrimer formed by TRAF1 CC and TRAF2, or a TRAF2 homotrimer (PubMed:11907583, PubMed:19506082, CC PubMed:20447407, PubMed:20385093). Identified in a complex composed of CC TRAF2, TRAF3, BIRC2 and BIRC3 (By similarity). Interacts with BIRC2; CC the interaction promotes BIRC2 stability (PubMed:19506082). Interaction CC with BIRC2 and/or BIRC3 is essential for ubiquitination of IKBKE, CC degradation of NFKBIA and activation of NF-kappa-B (By similarity). CC Within complex I, phosphorylated TRAF2 interacts (via 'Lys-63'-linked CC polyubiquitin chains) with CHUCK/IKK-alpha, IKBKB/IKK-beta, IKBKG/IKK- CC gamma TAB2, TAB3 and TAK1 in response to TNF-alpha stimulation CC (PubMed:19150425). Within complex I, interacts with UXT isoform 1 (via CC TPQE motif); the interaction prevents the recruitment of FADD and CC CASP8/caspase 8 to complex I (PubMed:21307340). Forms a complex CC composed of TNFRSF8/CD30 or TNFRSF1B/TNFR2, and TRAF1, TRAF2 and E3 CC ligase TRAIP (PubMed:9104814). Within the complex, interacts with CC TRAIP; the interaction inhibits TRAF2-mediated NF-kappa B activation CC (PubMed:9104814). Component of a complex composed of TANK and TBK1 CC (PubMed:10581243). Interacts with TRPC4AP (By similarity). Interacts CC with MAP3K1/MEKK1, MAP3K5/ASK1 and MAP3K11/MLK3 in response to TNF- CC alpha stimulation; the interaction leads to JNK activation and CC interaction with MAP3K5 is inhibited by PRMT1 (PubMed:10346818, CC PubMed:19918265, PubMed:9774977, PubMed:22095282). Component of a CC complex composed of MAP3K14/NIK BIRC3 and TRAF3; the interaction leads CC to BIRC2/3-mediated ubiquitination of TRAF3 upon CD40 engagement in a CC TRAF2-dependent manner (By similarity). Interacts with MAP3K14/NIK in CC response to TNF-alpha stimulation; the interaction leads to NF-kappa B CC activation (PubMed:9020361). Interacts with PEG3; the interaction may CC promote TRAF2-mediated NF-kappa B activation (By similarity). Interacts CC with HIVEP3; the interaction may inhibit TNF-alpha-TRAF2-mediated NF- CC kappa B and JNK activation (By similarity). Interacts with TANK/ITRAF; CC the interaction prevents interaction between TNFRSF1B/TNFR2 and TRAF2 CC (PubMed:8710854). Interacts with deubiquitinating enzyme CYLD; the CC interaction results in the deubiquitination and inactivation of TRAF2 CC (PubMed:12917691). Interacts with SIAH2; the interaction leads to TRAF2 CC ubiquitination and degradation (PubMed:12411493). Interacts with E2 CC conjugating enzyme UBE2N/Ubc13, E3 ligase ITCH and RNF11 in response to CC TNF-alpha stimulation (By similarity). Interacts with ubiquitin-editing CC enzyme TNFAIP3/A20 in response to TNF-alpha stimulation; the CC interaction promotes TRAF2 dissociation from UBE2N/Ubc13, ITCH, RNF11 CC and TAX1BP1 and prevents prolonged TRAF-2 ubiquitination (By CC similarity). Interacts with TAX1BP1 in response to TNF-alpha CC stimulation; the interaction promotes TRAF2 dissociation from CC UBE2N/Ubc13 and TNFAIP3/A20, and prevents prolonged TRAF-2 CC ubiquitination (By similarity). Interacts (via C-terminus) with CC EIF2AK2/PKR (via the kinase catalytic domain) (PubMed:15121867). CC Interacts with deubiquitinating enzyme USP48 (PubMed:16214042). CC Interacts with PTPN2; probably involved in TNF-mediated signaling CC (PubMed:15696169). Interacts with Toll-like receptor TLR4/3 adapter CC TICAM1/TRIF; the interaction may promote TICAM1 ubiquitination CC (PubMed:20047764). Interacts with kinase/endoribonuclease ERN1/IRE1 and CC DAB2IP in response to ER stress; the interaction requires DAB2IP (By CC similarity). Interacts with ERN1/IRE1 and TAOK3 in response to ER CC stress; the interaction may promote TRAF2 phosphorylation CC (PubMed:11278723). Interacts (via zinc fingers) with DAB2IP (via C- CC terminus PER domain)in response to TNF-alpha stimulation CC (PubMed:15310755, PubMed:17389591). Interacts with CASP8AP2/FLASH (By CC similarity). Interacts with NFATC2IP; the interaction may repress IL-4 CC production in T cells (By similarity). Interacts with kinase CDK9 CC (PubMed:9827693). Interacts with sphingosine kinase 1 SPHK1 CC (PubMed:20577214). Interacts with kinase TNIK (PubMed:10521462). CC Interacts with TRAFD1 (By similarity). Interacts with DNA CC phosphodiesterase TDP2 (PubMed:10764746). Interacts with MAVS/IPS1 CC (PubMed:16153868). Interacts with CARD14 (PubMed:21302310). Interacts CC with Epstein-Barr virus LMP1/BNFL1 (PubMed:10411888). Interacts with CC GPS2 (By similarity). Interacts with XPNPEP3 (PubMed:25609706). CC Interacts with RIPK3 (PubMed:29883609). Interacts with RELL2 CC (PubMed:19969290). Interacts with LRRC19 (PubMed:25026888). Interacts CC with GAPDH; promoting TRAF2 ubiquitination (PubMed:23332158). CC {ECO:0000250|UniProtKB:P39429, ECO:0000269|PubMed:10037686, CC ECO:0000269|PubMed:10206649, ECO:0000269|PubMed:10346818, CC ECO:0000269|PubMed:10411888, ECO:0000269|PubMed:10514511, CC ECO:0000269|PubMed:10521462, ECO:0000269|PubMed:10581243, CC ECO:0000269|PubMed:10764746, ECO:0000269|PubMed:10809768, CC ECO:0000269|PubMed:10880535, ECO:0000269|PubMed:10892748, CC ECO:0000269|PubMed:11035039, ECO:0000269|PubMed:11278723, CC ECO:0000269|PubMed:11907583, ECO:0000269|PubMed:12411493, CC ECO:0000269|PubMed:12917691, ECO:0000269|PubMed:15121867, CC ECO:0000269|PubMed:15310755, ECO:0000269|PubMed:15383523, CC ECO:0000269|PubMed:15696169, ECO:0000269|PubMed:16153868, CC ECO:0000269|PubMed:16214042, ECO:0000269|PubMed:17389591, CC ECO:0000269|PubMed:18981220, ECO:0000269|PubMed:19150425, CC ECO:0000269|PubMed:19506082, ECO:0000269|PubMed:19810754, CC ECO:0000269|PubMed:19918265, ECO:0000269|PubMed:19969290, CC ECO:0000269|PubMed:20047764, ECO:0000269|PubMed:20385093, CC ECO:0000269|PubMed:20447407, ECO:0000269|PubMed:20577214, CC ECO:0000269|PubMed:21302310, ECO:0000269|PubMed:21307340, CC ECO:0000269|PubMed:22095282, ECO:0000269|PubMed:23332158, CC ECO:0000269|PubMed:25026888, ECO:0000269|PubMed:25609706, CC ECO:0000269|PubMed:29883609, ECO:0000269|PubMed:7639698, CC ECO:0000269|PubMed:8069916, ECO:0000269|PubMed:8627180, CC ECO:0000269|PubMed:8710854, ECO:0000269|PubMed:9020361, CC ECO:0000269|PubMed:9104814, ECO:0000269|PubMed:9153189, CC ECO:0000269|PubMed:9418902, ECO:0000269|PubMed:9488716, CC ECO:0000269|PubMed:9607925, ECO:0000269|PubMed:9692890, CC ECO:0000269|PubMed:9705938, ECO:0000269|PubMed:9718306, CC ECO:0000269|PubMed:9774460, ECO:0000269|PubMed:9774977, CC ECO:0000269|PubMed:9827693}. CC -!- INTERACTION: CC Q12933; Q9NRN7: AASDHPPT; NbExp=7; IntAct=EBI-355744, EBI-740884; CC Q12933; Q9UHB7: AFF4; NbExp=3; IntAct=EBI-355744, EBI-395282; CC Q12933; Q9UHB7-2: AFF4; NbExp=3; IntAct=EBI-355744, EBI-10261324; CC Q12933; O95994: AGR2; NbExp=3; IntAct=EBI-355744, EBI-712648; CC Q12933; C9JRZ8-2: AKR1B15; NbExp=3; IntAct=EBI-355744, EBI-17190479; CC Q12933; Q9Y2J4-4: AMOTL2; NbExp=3; IntAct=EBI-355744, EBI-10187270; CC Q12933; X5D778: ANKRD11; NbExp=4; IntAct=EBI-355744, EBI-17183751; CC Q12933; Q96IX9: ANKRD36BP1; NbExp=4; IntAct=EBI-355744, EBI-744859; CC Q12933; Q9UKG1: APPL1; NbExp=3; IntAct=EBI-355744, EBI-741243; CC Q12933; P29972: AQP1; NbExp=3; IntAct=EBI-355744, EBI-745213; CC Q12933; Q15052: ARHGEF6; NbExp=3; IntAct=EBI-355744, EBI-1642523; CC Q12933; Q8N5N6: ARSJ; NbExp=3; IntAct=EBI-355744, EBI-10266832; CC Q12933; Q8N9N2: ASCC1; NbExp=3; IntAct=EBI-355744, EBI-10268317; CC Q12933; Q8N9N2-2: ASCC1; NbExp=3; IntAct=EBI-355744, EBI-10962548; CC Q12933; Q7L5A3: ATOSB; NbExp=3; IntAct=EBI-355744, EBI-745689; CC Q12933; P54253: ATXN1; NbExp=14; IntAct=EBI-355744, EBI-930964; CC Q12933; O15169: AXIN1; NbExp=3; IntAct=EBI-355744, EBI-710484; CC Q12933; Q8TBE0: BAHD1; NbExp=4; IntAct=EBI-355744, EBI-742750; CC Q12933; B4DE54: BANP; NbExp=3; IntAct=EBI-355744, EBI-16429313; CC Q12933; Q8N9N5: BANP; NbExp=4; IntAct=EBI-355744, EBI-744695; CC Q12933; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-355744, EBI-11524452; CC Q12933; Q8N9N5-7: BANP; NbExp=3; IntAct=EBI-355744, EBI-16429296; CC Q12933; Q9UIF8: BAZ2B; NbExp=3; IntAct=EBI-355744, EBI-741542; CC Q12933; O95999: BCL10; NbExp=9; IntAct=EBI-355744, EBI-958922; CC Q12933; P41182: BCL6; NbExp=3; IntAct=EBI-355744, EBI-765407; CC Q12933; Q9BXY8: BEX2; NbExp=6; IntAct=EBI-355744, EBI-745073; CC Q12933; Q13490: BIRC2; NbExp=17; IntAct=EBI-355744, EBI-514538; CC Q12933; Q13489: BIRC3; NbExp=7; IntAct=EBI-355744, EBI-517709; CC Q12933; Q8IYS8: BOD1L2; NbExp=3; IntAct=EBI-355744, EBI-12118438; CC Q12933; Q13895: BYSL; NbExp=3; IntAct=EBI-355744, EBI-358049; CC Q12933; Q8WYQ4-2: C22orf15; NbExp=3; IntAct=EBI-355744, EBI-12030460; CC Q12933; Q53TS8: C2CD6; NbExp=3; IntAct=EBI-355744, EBI-739879; CC Q12933; O75808: CAPN15; NbExp=3; IntAct=EBI-355744, EBI-6149008; CC Q12933; Q8NEC5: CATSPER1; NbExp=3; IntAct=EBI-355744, EBI-744545; CC Q12933; Q9HC52: CBX8; NbExp=6; IntAct=EBI-355744, EBI-712912; CC Q12933; E9PSE9: CCDC198; NbExp=3; IntAct=EBI-355744, EBI-11748295; CC Q12933; Q9NVL8: CCDC198; NbExp=3; IntAct=EBI-355744, EBI-10238351; CC Q12933; Q8TD31-3: CCHCR1; NbExp=8; IntAct=EBI-355744, EBI-10175300; CC Q12933; Q8IV13: CCNJL; NbExp=3; IntAct=EBI-355744, EBI-21668062; CC Q12933; P25942: CD40; NbExp=17; IntAct=EBI-355744, EBI-525714; CC Q12933; Q86Y33: CDC20B; NbExp=3; IntAct=EBI-355744, EBI-10260504; CC Q12933; Q86Y33-5: CDC20B; NbExp=3; IntAct=EBI-355744, EBI-11983537; CC Q12933; Q16543: CDC37; NbExp=3; IntAct=EBI-355744, EBI-295634; CC Q12933; Q99618: CDCA3; NbExp=7; IntAct=EBI-355744, EBI-739534; CC Q12933; Q07002: CDK18; NbExp=3; IntAct=EBI-355744, EBI-746238; CC Q12933; P46527: CDKN1B; NbExp=6; IntAct=EBI-355744, EBI-519280; CC Q12933; Q8IYX8-2: CEP57L1; NbExp=3; IntAct=EBI-355744, EBI-10181988; CC Q12933; Q9Y6H1: CHCHD2; NbExp=3; IntAct=EBI-355744, EBI-2321769; CC Q12933; P51800-3: CLCNKA; NbExp=3; IntAct=EBI-355744, EBI-11980535; CC Q12933; Q02930-3: CREB5; NbExp=6; IntAct=EBI-355744, EBI-10192698; CC Q12933; Q49AN0: CRY2; NbExp=3; IntAct=EBI-355744, EBI-2212355; CC Q12933; P53672: CRYBA2; NbExp=3; IntAct=EBI-355744, EBI-750444; CC Q12933; P49711: CTCF; NbExp=3; IntAct=EBI-355744, EBI-932887; CC Q12933; Q2TBE0: CWF19L2; NbExp=3; IntAct=EBI-355744, EBI-5453285; CC Q12933; Q6BCY4: CYB5R2; NbExp=3; IntAct=EBI-355744, EBI-744761; CC Q12933; Q6BCY4-2: CYB5R2; NbExp=3; IntAct=EBI-355744, EBI-12102608; CC Q12933; Q8WTU0: DDI1; NbExp=3; IntAct=EBI-355744, EBI-748248; CC Q12933; P26196: DDX6; NbExp=3; IntAct=EBI-355744, EBI-351257; CC Q12933; Q08495: DMTN; NbExp=3; IntAct=EBI-355744, EBI-715275; CC Q12933; O60941: DTNB; NbExp=5; IntAct=EBI-355744, EBI-740402; CC Q12933; O60941-5: DTNB; NbExp=3; IntAct=EBI-355744, EBI-11984733; CC Q12933; Q92997: DVL3; NbExp=3; IntAct=EBI-355744, EBI-739789; CC Q12933; Q13627: DYRK1A; NbExp=3; IntAct=EBI-355744, EBI-1053596; CC Q12933; Q96JC9: EAF1; NbExp=3; IntAct=EBI-355744, EBI-769261; CC Q12933; Q9HAK2: EBF2; NbExp=3; IntAct=EBI-355744, EBI-12267154; CC Q12933; Q8WWZ3: EDARADD; NbExp=5; IntAct=EBI-355744, EBI-2949647; CC Q12933; A0A0S2Z3V1: EFEMP1; NbExp=3; IntAct=EBI-355744, EBI-16434097; CC Q12933; Q12805: EFEMP1; NbExp=12; IntAct=EBI-355744, EBI-536772; CC Q12933; Q5JVL4: EFHC1; NbExp=6; IntAct=EBI-355744, EBI-743105; CC Q12933; P00533: EGFR; NbExp=4; IntAct=EBI-355744, EBI-297353; CC Q12933; Q08426: EHHADH; NbExp=3; IntAct=EBI-355744, EBI-2339219; CC Q12933; Q9H0I2: ENKD1; NbExp=7; IntAct=EBI-355744, EBI-744099; CC Q12933; A0A0A0MR80: EP400; NbExp=3; IntAct=EBI-355744, EBI-12089140; CC Q12933; O75460: ERN1; NbExp=3; IntAct=EBI-355744, EBI-371750; CC Q12933; A0A0S2Z3N6: ETV6; NbExp=3; IntAct=EBI-355744, EBI-16434659; CC Q12933; Q01844: EWSR1; NbExp=3; IntAct=EBI-355744, EBI-739737; CC Q12933; Q8N2X6: EXOC3-AS1; NbExp=4; IntAct=EBI-355744, EBI-749333; CC Q12933; O95990-4: FAM107A; NbExp=3; IntAct=EBI-355744, EBI-11977223; CC Q12933; Q96EK7: FAM120B; NbExp=4; IntAct=EBI-355744, EBI-739883; CC Q12933; Q9H5Z6-2: FAM124B; NbExp=3; IntAct=EBI-355744, EBI-11986315; CC Q12933; Q3B820: FAM161A; NbExp=3; IntAct=EBI-355744, EBI-719941; CC Q12933; Q96MY7: FAM161B; NbExp=3; IntAct=EBI-355744, EBI-7225287; CC Q12933; Q9Y247: FAM50B; NbExp=3; IntAct=EBI-355744, EBI-742802; CC Q12933; Q86YD7: FAM90A1; NbExp=6; IntAct=EBI-355744, EBI-6658203; CC Q12933; Q8IZU1: FAM9A; NbExp=3; IntAct=EBI-355744, EBI-8468186; CC Q12933; O95363: FARS2; NbExp=3; IntAct=EBI-355744, EBI-2513774; CC Q12933; Q9NVF7: FBXO28; NbExp=7; IntAct=EBI-355744, EBI-740282; CC Q12933; Q9BRP7: FDXACB1; NbExp=6; IntAct=EBI-355744, EBI-10297077; CC Q12933; Q4VC44: FLYWCH1; NbExp=3; IntAct=EBI-355744, EBI-719415; CC Q12933; Q53EP0-3: FNDC3B; NbExp=3; IntAct=EBI-355744, EBI-10242151; CC Q12933; O15353: FOXN1; NbExp=3; IntAct=EBI-355744, EBI-11319000; CC Q12933; Q06547: GABPB1; NbExp=7; IntAct=EBI-355744, EBI-618165; CC Q12933; Q8NHY3: GAS2L2; NbExp=3; IntAct=EBI-355744, EBI-7960826; CC Q12933; O95995: GAS8; NbExp=3; IntAct=EBI-355744, EBI-1052570; CC Q12933; P28676: GCA; NbExp=3; IntAct=EBI-355744, EBI-947242; CC Q12933; P55040: GEM; NbExp=3; IntAct=EBI-355744, EBI-744104; CC Q12933; Q9H8Y8: GORASP2; NbExp=8; IntAct=EBI-355744, EBI-739467; CC Q12933; O95872: GPANK1; NbExp=3; IntAct=EBI-355744, EBI-751540; CC Q12933; Q92917: GPKOW; NbExp=7; IntAct=EBI-355744, EBI-746309; CC Q12933; Q4V328: GRIPAP1; NbExp=3; IntAct=EBI-355744, EBI-717919; CC Q12933; Q14687: GSE1; NbExp=3; IntAct=EBI-355744, EBI-372619; CC Q12933; Q2KHT4: GSG1; NbExp=3; IntAct=EBI-355744, EBI-10239244; CC Q12933; P09211: GSTP1; NbExp=5; IntAct=EBI-355744, EBI-353467; CC Q12933; O43708: GSTZ1; NbExp=3; IntAct=EBI-355744, EBI-748043; CC Q12933; Q6B0K9: HBM; NbExp=3; IntAct=EBI-355744, EBI-12805802; CC Q12933; A0A024R8L2: hCG_1987119; NbExp=3; IntAct=EBI-355744, EBI-14103818; CC Q12933; Q5T8I9: HENMT1; NbExp=3; IntAct=EBI-355744, EBI-9675710; CC Q12933; P49639: HOXA1; NbExp=3; IntAct=EBI-355744, EBI-740785; CC Q12933; P09067: HOXB5; NbExp=3; IntAct=EBI-355744, EBI-3893317; CC Q12933; Q96MM6: HSPA12B; NbExp=3; IntAct=EBI-355744, EBI-10291310; CC Q12933; P42858: HTT; NbExp=3; IntAct=EBI-355744, EBI-466029; CC Q12933; P12268: IMPDH2; NbExp=3; IntAct=EBI-355744, EBI-353389; CC Q12933; Q9C086: INO80B; NbExp=3; IntAct=EBI-355744, EBI-715611; CC Q12933; Q96PC2: IP6K3; NbExp=3; IntAct=EBI-355744, EBI-10990676; CC Q12933; Q8NA54: IQUB; NbExp=3; IntAct=EBI-355744, EBI-10220600; CC Q12933; Q6GPH6-2: ITPRIPL1; NbExp=3; IntAct=EBI-355744, EBI-12337095; CC Q12933; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-355744, EBI-2556193; CC Q12933; Q5T5P2-6: KIAA1217; NbExp=3; IntAct=EBI-355744, EBI-10188326; CC Q12933; Q9BVG8: KIFC3; NbExp=3; IntAct=EBI-355744, EBI-2125614; CC Q12933; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-355744, EBI-14069005; CC Q12933; P57682: KLF3; NbExp=6; IntAct=EBI-355744, EBI-8472267; CC Q12933; Q96BZ8: LENG1; NbExp=3; IntAct=EBI-355744, EBI-726510; CC Q12933; Q86X59: LINC02875; NbExp=3; IntAct=EBI-355744, EBI-8465536; CC Q12933; Q8IXW0: LMNTD2; NbExp=3; IntAct=EBI-355744, EBI-12028858; CC Q12933; Q8TBB1: LNX1; NbExp=5; IntAct=EBI-355744, EBI-739832; CC Q12933; Q17RB8: LONRF1; NbExp=3; IntAct=EBI-355744, EBI-2341787; CC Q12933; Q496Y0: LONRF3; NbExp=3; IntAct=EBI-355744, EBI-2690768; CC Q12933; Q96S90: LYSMD1; NbExp=3; IntAct=EBI-355744, EBI-10293291; CC Q12933; O75367: MACROH2A1; NbExp=3; IntAct=EBI-355744, EBI-2868511; CC Q12933; Q99558: MAP3K14; NbExp=9; IntAct=EBI-355744, EBI-358011; CC Q12933; Q99683: MAP3K5; NbExp=4; IntAct=EBI-355744, EBI-476263; CC Q12933; Q7Z434: MAVS; NbExp=5; IntAct=EBI-355744, EBI-995373; CC Q12933; Q8N6R0: METTL13; NbExp=3; IntAct=EBI-355744, EBI-1053295; CC Q12933; P55081: MFAP1; NbExp=3; IntAct=EBI-355744, EBI-1048159; CC Q12933; Q8IVT4: MGC50722; NbExp=3; IntAct=EBI-355744, EBI-14086479; CC Q12933; Q8IVT2: MISP; NbExp=3; IntAct=EBI-355744, EBI-2555085; CC Q12933; Q13064: MKRN3; NbExp=3; IntAct=EBI-355744, EBI-2340269; CC Q12933; Q9UBU8-2: MORF4L1; NbExp=3; IntAct=EBI-355744, EBI-10288852; CC Q12933; Q6PF18: MORN3; NbExp=6; IntAct=EBI-355744, EBI-9675802; CC Q12933; P00540: MOS; NbExp=3; IntAct=EBI-355744, EBI-1757866; CC Q12933; Q9Y3D2: MSRB2; NbExp=3; IntAct=EBI-355744, EBI-9092052; CC Q12933; Q15742: NAB2; NbExp=3; IntAct=EBI-355744, EBI-8641936; CC Q12933; Q8N6N6: NATD1; NbExp=3; IntAct=EBI-355744, EBI-8656665; CC Q12933; O76041: NEBL; NbExp=7; IntAct=EBI-355744, EBI-2880203; CC Q12933; Q14511-2: NEDD9; NbExp=3; IntAct=EBI-355744, EBI-11746523; CC Q12933; Q9HC98-4: NEK6; NbExp=3; IntAct=EBI-355744, EBI-11750983; CC Q12933; Q16649: NFIL3; NbExp=3; IntAct=EBI-355744, EBI-3951858; CC Q12933; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-355744, EBI-10271199; CC Q12933; Q5HYW2: NHSL2; NbExp=3; IntAct=EBI-355744, EBI-2859639; CC Q12933; Q9GZQ4: NMUR2; NbExp=3; IntAct=EBI-355744, EBI-10303844; CC Q12933; Q86UR1-2: NOXA1; NbExp=3; IntAct=EBI-355744, EBI-12025760; CC Q12933; Q16656: NRF1; NbExp=3; IntAct=EBI-355744, EBI-2547810; CC Q12933; Q16656-4: NRF1; NbExp=3; IntAct=EBI-355744, EBI-11742836; CC Q12933; Q6X4W1-2: NSMF; NbExp=3; IntAct=EBI-355744, EBI-12028784; CC Q12933; Q9BRJ7: NUDT16L1; NbExp=6; IntAct=EBI-355744, EBI-2949792; CC Q12933; Q8N3R9: PALS1; NbExp=3; IntAct=EBI-355744, EBI-2513978; CC Q12933; Q9HBE1-4: PATZ1; NbExp=3; IntAct=EBI-355744, EBI-11022007; CC Q12933; P35227: PCGF2; NbExp=3; IntAct=EBI-355744, EBI-2129767; CC Q12933; Q86SE9: PCGF5; NbExp=3; IntAct=EBI-355744, EBI-2827999; CC Q12933; Q17RL8: PDZD4; NbExp=3; IntAct=EBI-355744, EBI-10239064; CC Q12933; Q96JS3: PGBD1; NbExp=7; IntAct=EBI-355744, EBI-10290053; CC Q12933; O75928-2: PIAS2; NbExp=3; IntAct=EBI-355744, EBI-348567; CC Q12933; Q4G0R1: PIBF1; NbExp=3; IntAct=EBI-355744, EBI-14066006; CC Q12933; Q13526: PIN1; NbExp=7; IntAct=EBI-355744, EBI-714158; CC Q12933; Q16512: PKN1; NbExp=3; IntAct=EBI-355744, EBI-602382; CC Q12933; Q9BUI4: POLR3C; NbExp=3; IntAct=EBI-355744, EBI-5452779; CC Q12933; Q96HA1-2: POM121; NbExp=3; IntAct=EBI-355744, EBI-11956563; CC Q12933; O60437: PPL; NbExp=6; IntAct=EBI-355744, EBI-368321; CC Q12933; Q6NYC8: PPP1R18; NbExp=3; IntAct=EBI-355744, EBI-2557469; CC Q12933; Q5T8A7: PPP1R26; NbExp=3; IntAct=EBI-355744, EBI-308500; CC Q12933; O43741: PRKAB2; NbExp=8; IntAct=EBI-355744, EBI-1053424; CC Q12933; Q9H875: PRKRIP1; NbExp=3; IntAct=EBI-355744, EBI-744488; CC Q12933; Q99633: PRPF18; NbExp=3; IntAct=EBI-355744, EBI-2798416; CC Q12933; P20618: PSMB1; NbExp=5; IntAct=EBI-355744, EBI-372273; CC Q12933; O00233: PSMD9; NbExp=3; IntAct=EBI-355744, EBI-750973; CC Q12933; Q9GZU8: PSME3IP1; NbExp=3; IntAct=EBI-355744, EBI-2371956; CC Q12933; P47897: QARS1; NbExp=3; IntAct=EBI-355744, EBI-347462; CC Q12933; Q2TAL8: QRICH1; NbExp=3; IntAct=EBI-355744, EBI-2798044; CC Q12933; P54725: RAD23A; NbExp=8; IntAct=EBI-355744, EBI-746453; CC Q12933; Q9Y4B4: RAD54L2; NbExp=3; IntAct=EBI-355744, EBI-948156; CC Q12933; Q8WWW0: RASSF5; NbExp=3; IntAct=EBI-355744, EBI-367390; CC Q12933; Q96IZ5: RBM41; NbExp=6; IntAct=EBI-355744, EBI-740773; CC Q12933; Q9P2K3: RCOR3; NbExp=4; IntAct=EBI-355744, EBI-743428; CC Q12933; P48380: RFX3; NbExp=5; IntAct=EBI-355744, EBI-742557; CC Q12933; Q13671: RIN1; NbExp=3; IntAct=EBI-355744, EBI-366017; CC Q12933; Q13546: RIPK1; NbExp=8; IntAct=EBI-355744, EBI-358507; CC Q12933; O43353: RIPK2; NbExp=2; IntAct=EBI-355744, EBI-358522; CC Q12933; Q0D2K3: RIPPLY1; NbExp=6; IntAct=EBI-355744, EBI-10226430; CC Q12933; P57055: RIPPLY3; NbExp=3; IntAct=EBI-355744, EBI-12092053; CC Q12933; Q9NTX7: RNF146; NbExp=3; IntAct=EBI-355744, EBI-722397; CC Q12933; Q9NTX7-2: RNF146; NbExp=3; IntAct=EBI-355744, EBI-11750630; CC Q12933; P78317: RNF4; NbExp=3; IntAct=EBI-355744, EBI-2340927; CC Q12933; Q9UHP6: RSPH14; NbExp=3; IntAct=EBI-355744, EBI-748350; CC Q12933; Q96NU1: SAMD11; NbExp=3; IntAct=EBI-355744, EBI-14067109; CC Q12933; Q7Z5V6-2: SAXO4; NbExp=3; IntAct=EBI-355744, EBI-12000762; CC Q12933; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-355744, EBI-748391; CC Q12933; Q9H788: SH2D4A; NbExp=3; IntAct=EBI-355744, EBI-747035; CC Q12933; Q92529: SHC3; NbExp=3; IntAct=EBI-355744, EBI-79084; CC Q12933; P48751: SLC4A3; NbExp=3; IntAct=EBI-355744, EBI-20805570; CC Q12933; Q9H0W8: SMG9; NbExp=6; IntAct=EBI-355744, EBI-2872322; CC Q12933; O95863: SNAI1; NbExp=3; IntAct=EBI-355744, EBI-1045459; CC Q12933; Q9BV90: SNRNP25; NbExp=3; IntAct=EBI-355744, EBI-9675976; CC Q12933; Q9UN79: SOX13; NbExp=3; IntAct=EBI-355744, EBI-3928516; CC Q12933; P41225: SOX3; NbExp=3; IntAct=EBI-355744, EBI-9078386; CC Q12933; P35711-4: SOX5; NbExp=3; IntAct=EBI-355744, EBI-11954419; CC Q12933; Q9NZD8: SPG21; NbExp=8; IntAct=EBI-355744, EBI-742688; CC Q12933; P63165: SUMO1; NbExp=3; IntAct=EBI-355744, EBI-80140; CC Q12933; G2XKQ0: SUMO1P1; NbExp=3; IntAct=EBI-355744, EBI-10175576; CC Q12933; Q9BSW7: SYT17; NbExp=6; IntAct=EBI-355744, EBI-745392; CC Q12933; Q5T7P8-2: SYT6; NbExp=3; IntAct=EBI-355744, EBI-10246152; CC Q12933; Q92844: TANK; NbExp=8; IntAct=EBI-355744, EBI-356349; CC Q12933; Q9H2K8: TAOK3; NbExp=2; IntAct=EBI-355744, EBI-1384100; CC Q12933; Q9UHD2: TBK1; NbExp=7; IntAct=EBI-355744, EBI-356402; CC Q12933; Q9Y4C2-2: TCAF1; NbExp=3; IntAct=EBI-355744, EBI-11974855; CC Q12933; O15273: TCAP; NbExp=3; IntAct=EBI-355744, EBI-954089; CC Q12933; Q15560: TCEA2; NbExp=7; IntAct=EBI-355744, EBI-710310; CC Q12933; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-355744, EBI-11955057; CC Q12933; P56279: TCL1A; NbExp=3; IntAct=EBI-355744, EBI-749995; CC Q12933; Q9BXF9: TEKT3; NbExp=6; IntAct=EBI-355744, EBI-8644516; CC Q12933; Q9BT49: THAP7; NbExp=13; IntAct=EBI-355744, EBI-741350; CC Q12933; Q96CV8: THOP1; NbExp=3; IntAct=EBI-355744, EBI-6137619; CC Q12933; Q96CG3: TIFA; NbExp=12; IntAct=EBI-355744, EBI-740711; CC Q12933; Q8IY51: TIGD4; NbExp=3; IntAct=EBI-355744, EBI-12117432; CC Q12933; Q08117: TLE5; NbExp=3; IntAct=EBI-355744, EBI-717810; CC Q12933; P21580: TNFAIP3; NbExp=10; IntAct=EBI-355744, EBI-527670; CC Q12933; Q9Y6Q6: TNFRSF11A; NbExp=2; IntAct=EBI-355744, EBI-525675; CC Q12933; Q9Y6Q6-2: TNFRSF11A; NbExp=5; IntAct=EBI-355744, EBI-20899422; CC Q12933; Q9NP84: TNFRSF12A; NbExp=3; IntAct=EBI-355744, EBI-2851995; CC Q12933; Q92956: TNFRSF14; NbExp=2; IntAct=EBI-355744, EBI-1056653; CC Q12933; P20333: TNFRSF1B; NbExp=3; IntAct=EBI-355744, EBI-358983; CC Q12933; Q9UKE5: TNIK; NbExp=2; IntAct=EBI-355744, EBI-1051794; CC Q12933; Q15628: TRADD; NbExp=13; IntAct=EBI-355744, EBI-359215; CC Q12933; Q13077: TRAF1; NbExp=11; IntAct=EBI-355744, EBI-359224; CC Q12933; Q12933: TRAF2; NbExp=11; IntAct=EBI-355744, EBI-355744; CC Q12933; O00463: TRAF5; NbExp=5; IntAct=EBI-355744, EBI-523498; CC Q12933; Q9Y4K3: TRAF6; NbExp=9; IntAct=EBI-355744, EBI-359276; CC Q12933; Q14142: TRIM14; NbExp=3; IntAct=EBI-355744, EBI-2820256; CC Q12933; Q8IWZ5: TRIM42; NbExp=3; IntAct=EBI-355744, EBI-5235829; CC Q12933; Q86XT4: TRIM50; NbExp=3; IntAct=EBI-355744, EBI-9867283; CC Q12933; Q12815: TROAP; NbExp=5; IntAct=EBI-355744, EBI-2349743; CC Q12933; Q86TN4-2: TRPT1; NbExp=3; IntAct=EBI-355744, EBI-12403619; CC Q12933; Q3SY00: TSGA10IP; NbExp=3; IntAct=EBI-355744, EBI-10241197; CC Q12933; Q9NRE2: TSHZ2; NbExp=3; IntAct=EBI-355744, EBI-10687282; CC Q12933; Q63HK5: TSHZ3; NbExp=3; IntAct=EBI-355744, EBI-9053916; CC Q12933; Q9Y5U2: TSSC4; NbExp=3; IntAct=EBI-355744, EBI-717229; CC Q12933; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-355744, EBI-9090990; CC Q12933; P10599: TXN; NbExp=3; IntAct=EBI-355744, EBI-594644; CC Q12933; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-355744, EBI-10180829; CC Q12933; Q5T124: UBXN11; NbExp=5; IntAct=EBI-355744, EBI-746004; CC Q12933; Q5T124-6: UBXN11; NbExp=3; IntAct=EBI-355744, EBI-11524408; CC Q12933; P22415: USF1; NbExp=3; IntAct=EBI-355744, EBI-1054489; CC Q12933; O75604: USP2; NbExp=7; IntAct=EBI-355744, EBI-743272; CC Q12933; Q5TAP6: UTP14C; NbExp=3; IntAct=EBI-355744, EBI-11737646; CC Q12933; Q9BRU9: UTP23; NbExp=3; IntAct=EBI-355744, EBI-5457544; CC Q12933; Q14119: VEZF1; NbExp=3; IntAct=EBI-355744, EBI-11980193; CC Q12933; Q5GFL6: VWA2; NbExp=3; IntAct=EBI-355744, EBI-10243723; CC Q12933; Q92558: WASF1; NbExp=3; IntAct=EBI-355744, EBI-1548747; CC Q12933; P07947: YES1; NbExp=6; IntAct=EBI-355744, EBI-515331; CC Q12933; Q05516: ZBTB16; NbExp=5; IntAct=EBI-355744, EBI-711925; CC Q12933; O43167: ZBTB24; NbExp=3; IntAct=EBI-355744, EBI-744471; CC Q12933; P24278: ZBTB25; NbExp=4; IntAct=EBI-355744, EBI-739899; CC Q12933; Q6ZSB9: ZBTB49; NbExp=3; IntAct=EBI-355744, EBI-2859943; CC Q12933; Q53FD0: ZC2HC1C; NbExp=3; IntAct=EBI-355744, EBI-740767; CC Q12933; Q53FD0-2: ZC2HC1C; NbExp=3; IntAct=EBI-355744, EBI-14104088; CC Q12933; Q6FIF0: ZFAND6; NbExp=7; IntAct=EBI-355744, EBI-724630; CC Q12933; Q9BRR0: ZKSCAN3; NbExp=3; IntAct=EBI-355744, EBI-1965777; CC Q12933; Q96NC0: ZMAT2; NbExp=6; IntAct=EBI-355744, EBI-2682299; CC Q12933; Q9UJ78-2: ZMYM5; NbExp=3; IntAct=EBI-355744, EBI-17634549; CC Q12933; P15622-3: ZNF250; NbExp=3; IntAct=EBI-355744, EBI-10177272; CC Q12933; P13682: ZNF35; NbExp=3; IntAct=EBI-355744, EBI-11041653; CC Q12933; Q86VK4: ZNF410; NbExp=3; IntAct=EBI-355744, EBI-720304; CC Q12933; Q86VK4-3: ZNF410; NbExp=3; IntAct=EBI-355744, EBI-11741890; CC Q12933; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-355744, EBI-740727; CC Q12933; Q7Z4V0: ZNF438; NbExp=3; IntAct=EBI-355744, EBI-11962468; CC Q12933; Q96MN9: ZNF488; NbExp=3; IntAct=EBI-355744, EBI-948288; CC Q12933; Q32MK9: ZNF509; NbExp=3; IntAct=EBI-355744, EBI-10239929; CC Q12933; Q6NX49: ZNF544; NbExp=4; IntAct=EBI-355744, EBI-2841978; CC Q12933; Q7Z3I7: ZNF572; NbExp=3; IntAct=EBI-355744, EBI-10172590; CC Q12933; Q6ZN55-2: ZNF574; NbExp=3; IntAct=EBI-355744, EBI-17189720; CC Q12933; Q5T619: ZNF648; NbExp=3; IntAct=EBI-355744, EBI-11985915; CC Q12933; Q8N720: ZNF655; NbExp=3; IntAct=EBI-355744, EBI-625509; CC Q12933; Q6ZS27-3: ZNF662; NbExp=3; IntAct=EBI-355744, EBI-10255155; CC Q12933; A0A0S2Z6P0: ZNF688; NbExp=3; IntAct=EBI-355744, EBI-16429989; CC Q12933; Q6NX45: ZNF774; NbExp=3; IntAct=EBI-355744, EBI-10251462; CC Q12933; Q3MJ62: ZSCAN23; NbExp=6; IntAct=EBI-355744, EBI-5667532; CC Q12933; Q9NX65: ZSCAN32; NbExp=3; IntAct=EBI-355744, EBI-739949; CC Q12933; Q96MP5: ZSWIM3; NbExp=3; IntAct=EBI-355744, EBI-5235554; CC Q12933; Q8IYH5: ZZZ3; NbExp=3; IntAct=EBI-355744, EBI-2795524; CC Q12933; A0A384ME25; NbExp=3; IntAct=EBI-355744, EBI-10211777; CC Q12933; B2R8Y4; NbExp=3; IntAct=EBI-355744, EBI-10175581; CC Q12933; O08736: Casp12; Xeno; NbExp=6; IntAct=EBI-355744, EBI-6140033; CC Q12933; P09022: Hoxa1; Xeno; NbExp=3; IntAct=EBI-355744, EBI-3957603; CC Q12933; Q62925: Map3k1; Xeno; NbExp=2; IntAct=EBI-355744, EBI-636664; CC Q12933; P07174: Ngfr; Xeno; NbExp=3; IntAct=EBI-355744, EBI-1038810; CC Q12933; P89055: NSP1; Xeno; NbExp=3; IntAct=EBI-355744, EBI-9522973; CC Q12933; PRO_0000449631 [P0DTD1]: rep; Xeno; NbExp=3; IntAct=EBI-355744, EBI-25475920; CC Q12933; P20334: Tnfrsf9; Xeno; NbExp=2; IntAct=EBI-355744, EBI-520693; CC Q12933; P70191: Traf5; Xeno; NbExp=2; IntAct=EBI-355744, EBI-523899; CC Q12933; P88961; Xeno; NbExp=3; IntAct=EBI-355744, EBI-7907665; CC Q12933-2; Q92956: TNFRSF14; NbExp=4; IntAct=EBI-355760, EBI-1056653; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15383523, CC ECO:0000269|PubMed:19150425}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q12933-1; Sequence=Displayed; CC Name=2; CC IsoId=Q12933-2; Sequence=VSP_007401; CC Name=3; CC IsoId=Q12933-3; Sequence=VSP_039687; CC Name=4; CC IsoId=Q12933-4; Sequence=VSP_039688; CC -!- DOMAIN: The coiled coil domain mediates homo- and hetero- CC oligomerization. {ECO:0000269|PubMed:20064526}. CC -!- DOMAIN: The MATH/TRAF domain binds to receptor cytoplasmic domains. CC {ECO:0000269|PubMed:20064526}. CC -!- DOMAIN: The RING-type zinc finger domain is essential for E3 ubiquitin- CC protein ligase activity. It is not essential for the stabilization of CC BIRC2, or for the ubiquitination of RIPK1 in response to TNFR1 CC signaling. {ECO:0000269|PubMed:20064526}. CC -!- PTM: Phosphorylated at several serine residues within the first 128 CC amino acid residues. Phosphorylated at Thr-117 in response to signaling CC via TNF and TNFRSF1A. Phosphorylation at Thr-117 is required for 'Lys- CC 63'-linked polyubiquitination, but not for 'Lys-48'-linked CC polyubiquitination. Phosphorylation at Thr-117 is important for CC interaction with IKKA and IKKB, activation of IKK and subsequent CC activation of NF-kappa-B. {ECO:0000269|PubMed:19150425}. CC -!- PTM: Undergoes both 'Lys-48'-linked and 'Lys-63'-linked CC polyubiquitination. Polyubiquitinated via 'Lys-63'-linked ubiquitin in CC response to TNF signaling; this requires prior phosphorylation at Thr- CC 117. 'Lys-63'-linked polyubiquitination promotes TRAF2-mediated CC activation of NF-kappa-B. Can be polyubiquitinated at several Lys CC residues via 'Lys-48'-linked ubiquitin chains in response to TNF CC signaling, leading to proteasomal degradation. Autoubiquitinated, CC leading to its subsequent proteasomal degradation. Polyubiquitinated by CC BIRC2 and SIAH2, leading to its subsequent proteasomal degradation. CC Deubiquitinated by CYLD, a protease that specifically cleaves 'Lys-63'- CC linked polyubiquitin chains. Ubiquination is inhibited by LRRC19; CC inhibits proteasomal degradation (PubMed:25026888). Ubiquitinated at CC Lys-320 by the SCF(FBXL2) complex, leading to its degradation by the CC proteasome (By similarity). Ubiquitinated by E3 ubiquitin-protein CC ligase complex containing FBXO7; leading to repression of NF-kappa-B CC signaling (PubMed:22212761). {ECO:0000250|UniProtKB:P39429, CC ECO:0000269|PubMed:19150425, ECO:0000269|PubMed:22212761, CC ECO:0000269|PubMed:25026888}. CC -!- SIMILARITY: Belongs to the TNF receptor-associated factor family. A CC subfamily. {ECO:0000305}. CC -!- CAUTION: Was reported to interact with IL15RA (PubMed:10463949). CC However, this work was later retracted (PubMed:21357251). CC {ECO:0000305|PubMed:10463949, ECO:0000305|PubMed:21357251}. CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/traf2/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U12597; AAA87706.1; -; mRNA. DR EMBL; AK054686; BAB70792.1; -; mRNA. DR EMBL; AK289722; BAF82411.1; -; mRNA. DR EMBL; AK298370; BAG60609.1; -; mRNA. DR EMBL; BX538160; CAD98040.1; -; mRNA. DR EMBL; AY623660; AAT27320.1; -; Genomic_DNA. DR EMBL; AL355987; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL449425; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471090; EAW88299.1; -; Genomic_DNA. DR EMBL; BC032410; AAH32410.1; -; mRNA. DR EMBL; BC033810; AAH33810.1; -; mRNA. DR EMBL; BC043492; AAH43492.1; -; mRNA. DR EMBL; BC064662; AAH64662.1; -; mRNA. DR CCDS; CCDS7013.1; -. [Q12933-1] DR PIR; S56163; S56163. DR RefSeq; NP_066961.2; NM_021138.3. [Q12933-1] DR RefSeq; XP_011517276.1; XM_011518974.2. DR RefSeq; XP_011517277.1; XM_011518975.2. DR RefSeq; XP_011517278.1; XM_011518976.2. [Q12933-1] DR RefSeq; XP_011517279.1; XM_011518977.2. [Q12933-1] DR RefSeq; XP_011517280.1; XM_011518978.2. DR RefSeq; XP_016870584.1; XM_017015095.1. DR PDB; 1CA4; X-ray; 2.20 A; A/B/C/D/E/F=334-501. DR PDB; 1CA9; X-ray; 2.30 A; A/B/C/D/E/F=310-501. DR PDB; 1CZY; X-ray; 2.00 A; A/B/C=334-501. DR PDB; 1CZZ; X-ray; 2.70 A; A/B/C=315-501. DR PDB; 1D00; X-ray; 2.00 A; A/B/C/D/E/F/G/H=334-501. DR PDB; 1D01; X-ray; 2.00 A; A/B/C/D/E/F=334-501. DR PDB; 1D0A; X-ray; 2.00 A; A/B/C/D/E/F=334-501. DR PDB; 1D0J; X-ray; 2.50 A; A/B/C/D/E/F=334-501. DR PDB; 1F3V; X-ray; 2.00 A; B=331-501. DR PDB; 1QSC; X-ray; 2.40 A; A/B/C=311-501. DR PDB; 3KNV; X-ray; 1.90 A; A=1-133. DR PDB; 3M06; X-ray; 2.67 A; A/B/C/D/E/F=266-329. DR PDB; 3M0A; X-ray; 2.61 A; A/B/C=266-329. DR PDB; 3M0D; X-ray; 2.80 A; A/B=266-329. DR PDB; 8T5Q; X-ray; 1.90 A; A/B/C/D/E/F=315-501. DR PDBsum; 1CA4; -. DR PDBsum; 1CA9; -. DR PDBsum; 1CZY; -. DR PDBsum; 1CZZ; -. DR PDBsum; 1D00; -. DR PDBsum; 1D01; -. DR PDBsum; 1D0A; -. DR PDBsum; 1D0J; -. DR PDBsum; 1F3V; -. DR PDBsum; 1QSC; -. DR PDBsum; 3KNV; -. DR PDBsum; 3M06; -. DR PDBsum; 3M0A; -. DR PDBsum; 3M0D; -. DR PDBsum; 8T5Q; -. DR AlphaFoldDB; Q12933; -. DR SMR; Q12933; -. DR BioGRID; 113038; 608. DR CORUM; Q12933; -. DR DIP; DIP-6223N; -. DR ELM; Q12933; -. DR IntAct; Q12933; 443. DR MINT; Q12933; -. DR STRING; 9606.ENSP00000247668; -. DR GlyGen; Q12933; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q12933; -. DR MetOSite; Q12933; -. DR PhosphoSitePlus; Q12933; -. DR BioMuta; TRAF2; -. DR DMDM; 23503103; -. DR EPD; Q12933; -. DR jPOST; Q12933; -. DR MassIVE; Q12933; -. DR MaxQB; Q12933; -. DR PaxDb; 9606-ENSP00000247668; -. DR PeptideAtlas; Q12933; -. DR ProteomicsDB; 59035; -. [Q12933-1] DR ProteomicsDB; 59036; -. [Q12933-2] DR ProteomicsDB; 59037; -. [Q12933-3] DR ProteomicsDB; 59038; -. [Q12933-4] DR Pumba; Q12933; -. DR Antibodypedia; 2422; 844 antibodies from 49 providers. DR DNASU; 7186; -. DR Ensembl; ENST00000247668.7; ENSP00000247668.2; ENSG00000127191.18. [Q12933-1] DR GeneID; 7186; -. DR KEGG; hsa:7186; -. DR MANE-Select; ENST00000247668.7; ENSP00000247668.2; NM_021138.4; NP_066961.2. DR UCSC; uc004cjv.4; human. [Q12933-1] DR AGR; HGNC:12032; -. DR CTD; 7186; -. DR DisGeNET; 7186; -. DR GeneCards; TRAF2; -. DR HGNC; HGNC:12032; TRAF2. DR HPA; ENSG00000127191; Low tissue specificity. DR MIM; 601895; gene. DR neXtProt; NX_Q12933; -. DR OpenTargets; ENSG00000127191; -. DR PharmGKB; PA164742666; -. DR VEuPathDB; HostDB:ENSG00000127191; -. DR eggNOG; KOG0297; Eukaryota. DR GeneTree; ENSGT00940000156621; -. DR HOGENOM; CLU_021061_4_1_1; -. DR InParanoid; Q12933; -. DR OMA; INEGCSW; -. DR OrthoDB; 2913784at2759; -. DR PhylomeDB; Q12933; -. DR TreeFam; TF321154; -. DR PathwayCommons; Q12933; -. DR Reactome; R-HSA-140534; Caspase activation via Death Receptors in the presence of ligand. DR Reactome; R-HSA-3371378; Regulation by c-FLIP. DR Reactome; R-HSA-5213460; RIPK1-mediated regulated necrosis. DR Reactome; R-HSA-5218900; CASP8 activity is inhibited. DR Reactome; R-HSA-5357786; TNFR1-induced proapoptotic signaling. DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling. DR Reactome; R-HSA-5357956; TNFR1-induced NF-kappa-B signaling pathway. DR Reactome; R-HSA-5668541; TNFR2 non-canonical NF-kB pathway. DR Reactome; R-HSA-5675482; Regulation of necroptotic cell death. DR Reactome; R-HSA-5676594; TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR Reactome; R-HSA-69416; Dimerization of procaspase-8. DR Reactome; R-HSA-75893; TNF signaling. DR Reactome; R-HSA-933541; TRAF6 mediated IRF7 activation. DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation. DR Reactome; R-HSA-9693928; Defective RIPK1-mediated regulated necrosis. DR Reactome; R-HSA-9758274; Regulation of NF-kappa B signaling. DR SignaLink; Q12933; -. DR SIGNOR; Q12933; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 7186; 178 hits in 1204 CRISPR screens. DR ChiTaRS; TRAF2; human. DR EvolutionaryTrace; Q12933; -. DR GeneWiki; TRAF2; -. DR GenomeRNAi; 7186; -. DR Pharos; Q12933; Tbio. DR PRO; PR:Q12933; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q12933; Protein. DR Bgee; ENSG00000127191; Expressed in lower esophagus mucosa and 123 other cell types or tissues. DR ExpressionAtlas; Q12933; baseline and differential. DR GO; GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL. DR GO; GO:0005938; C:cell cortex; IEA:Ensembl. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISS:BHF-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:1990604; C:IRE1-TRAF2-ASK1 complex; IDA:ParkinsonsUK-UCL. DR GO; GO:0045121; C:membrane raft; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0097057; C:TRAF2-GSTP1 complex; IDA:UniProtKB. DR GO; GO:0002947; C:tumor necrosis factor receptor superfamily complex; IDA:UniProtKB. DR GO; GO:0000151; C:ubiquitin ligase complex; IPI:ParkinsonsUK-UCL. DR GO; GO:0012506; C:vesicle membrane; IEA:Ensembl. DR GO; GO:0005174; F:CD40 receptor binding; ISS:BHF-UCL. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IEA:Ensembl. DR GO; GO:0060090; F:molecular adaptor activity; IDA:UniProt. DR GO; GO:0019901; F:protein kinase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IPI:GO_Central. DR GO; GO:0035591; F:signaling adaptor activity; IEA:Ensembl. DR GO; GO:0046625; F:sphingolipid binding; IDA:UniProtKB. DR GO; GO:0031996; F:thioesterase binding; IPI:UniProtKB. DR GO; GO:0043120; F:tumor necrosis factor binding; IPI:UniProtKB. DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IPI:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IDA:UniProt. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0007250; P:activation of NF-kappaB-inducing kinase activity; IMP:UniProtKB. DR GO; GO:0071732; P:cellular response to nitric oxide; IEA:Ensembl. DR GO; GO:0045087; P:innate immune response; IDA:UniProt. DR GO; GO:0097400; P:interleukin-17-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; TAS:ParkinsonsUK-UCL. DR GO; GO:0048255; P:mRNA stabilization; IEA:Ensembl. DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; IEA:Ensembl. DR GO; GO:0038061; P:non-canonical NF-kappaB signal transduction; IDA:UniProt. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IBA:GO_Central. DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:BHF-UCL. DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IMP:UniProtKB. DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IDA:UniProtKB. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:0002726; P:positive regulation of T cell cytokine production; IMP:UniProtKB. DR GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0097300; P:programmed necrotic cell death; IEA:Ensembl. DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB. DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl. DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0065003; P:protein-containing complex assembly; ISS:BHF-UCL. DR GO; GO:0042981; P:regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0002637; P:regulation of immunoglobulin production; IEA:Ensembl. DR GO; GO:0046328; P:regulation of JNK cascade; IEA:Ensembl. DR GO; GO:0043254; P:regulation of protein-containing complex assembly; IMP:UniProtKB. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; NAS:ParkinsonsUK-UCL. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IEA:Ensembl. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB. DR CDD; cd03778; MATH_TRAF2; 1. DR CDD; cd16639; RING-HC_TRAF2; 1. DR Gene3D; 1.20.5.170; -; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 3. DR InterPro; IPR002083; MATH/TRAF_dom. DR InterPro; IPR012227; TNF_rcpt-assoc_TRAF_met. DR InterPro; IPR008974; TRAF-like. DR InterPro; IPR037305; TRAF2_MATH. DR InterPro; IPR027133; TRAF2_RING-HC. DR InterPro; IPR049441; TRAF2_Znf. DR InterPro; IPR032070; TRAF_BIRC3-bd. DR InterPro; IPR049342; TRAF_MEP1_MATH_dom. DR InterPro; IPR018957; Znf_C3HC4_RING-type. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR InterPro; IPR001293; Znf_TRAF. DR PANTHER; PTHR10131; TNF RECEPTOR ASSOCIATED FACTOR; 1. DR PANTHER; PTHR10131:SF21; TNF RECEPTOR-ASSOCIATED FACTOR 2; 1. DR Pfam; PF21355; TRAF-mep_MATH; 1. DR Pfam; PF21341; TRAF2_zf; 1. DR Pfam; PF16673; TRAF_BIRC3_bd; 1. DR Pfam; PF00097; zf-C3HC4; 1. DR Pfam; PF02176; zf-TRAF; 1. DR PIRSF; PIRSF015614; TRAF; 1. DR SMART; SM00061; MATH; 1. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR SUPFAM; SSF49599; TRAF domain-like; 1. DR SUPFAM; SSF57953; Trimerization domain of TRAF; 1. DR PROSITE; PS50144; MATH; 1. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. DR PROSITE; PS50145; ZF_TRAF; 2. DR Genevisible; Q12933; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; Coiled coil; KW Cytoplasm; Isopeptide bond; Lipid-binding; Metal-binding; Phosphoprotein; KW Reference proteome; Repeat; Transferase; Ubl conjugation; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692" FT CHAIN 2..501 FT /note="TNF receptor-associated factor 2" FT /id="PRO_0000056399" FT DOMAIN 351..496 FT /note="MATH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00129" FT ZN_FING 34..73 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT ZN_FING 124..180 FT /note="TRAF-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00207" FT ZN_FING 177..233 FT /note="TRAF-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00207" FT REGION 283..293 FT /note="Important for interaction with BIRC2 and BIRC3" FT /evidence="ECO:0000250" FT COILED 299..348 FT /evidence="ECO:0000269|PubMed:20385093" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692" FT MOD_RES 5 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 7 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 11 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:18981220, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 22 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 117 FT /note="Phosphothreonine; by PKC" FT /evidence="ECO:0000269|PubMed:19150425" FT CROSSLNK 31 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:19150425" FT CROSSLNK 320 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P39429" FT VAR_SEQ 53..63 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_039687" FT VAR_SEQ 122 FT /note="E -> EVKMPACGMVTEAPAVGSRPRSPSSYDLVLHVPLTGAEACLMSVEEE FT TELLLR (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_007401" FT VAR_SEQ 176..200 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_039688" FT MUTAGEN 11 FT /note="S->A: Reduces global phosphorylation. Partial FT reduction of TNF-dependent activation of NF-kappa-B and FT activation of JNK." FT /evidence="ECO:0000269|PubMed:18981220" FT MUTAGEN 11 FT /note="S->D: Slight increase of TNF-dependent activation of FT NF-kappa-B and activation of JNK." FT /evidence="ECO:0000269|PubMed:18981220" FT MUTAGEN 31 FT /note="K->R: Abolishes 'Lys-63'-linked polyubiquitination." FT MUTAGEN 117 FT /note="T->A: Loss of phosphorylation site. Abolishes FT activation of NF-kappa-B." FT /evidence="ECO:0000269|PubMed:19150425" FT MUTAGEN 285 FT /note="I->A: Strongly reduced interaction with BIRC3." FT /evidence="ECO:0000269|PubMed:20385093" FT MUTAGEN 288 FT /note="V->A: Strongly reduced interaction with BIRC3." FT /evidence="ECO:0000269|PubMed:20385093" FT MUTAGEN 292 FT /note="E->A: Strongly reduced interaction with BIRC3." FT /evidence="ECO:0000269|PubMed:20385093" FT CONFLICT 205..310 FT /note="Missing (in Ref. 2; BAB70792)" FT /evidence="ECO:0000305" FT CONFLICT 343..365 FT /note="LEMEASTYDGVFIWKISDFARKR -> RPFQAQCGHRYCSFCLASILRKL FT (in Ref. 1; AAA87706)" FT /evidence="ECO:0000305" FT HELIX 21..23 FT /evidence="ECO:0007829|PDB:3KNV" FT HELIX 25..27 FT /evidence="ECO:0007829|PDB:3KNV" FT HELIX 30..32 FT /evidence="ECO:0007829|PDB:3KNV" FT TURN 35..37 FT /evidence="ECO:0007829|PDB:3KNV" FT STRAND 42..46 FT /evidence="ECO:0007829|PDB:3KNV" FT STRAND 52..54 FT /evidence="ECO:0007829|PDB:3KNV" FT HELIX 55..61 FT /evidence="ECO:0007829|PDB:3KNV" FT HELIX 62..64 FT /evidence="ECO:0007829|PDB:3KNV" FT HELIX 70..74 FT /evidence="ECO:0007829|PDB:3KNV" FT TURN 80..83 FT /evidence="ECO:0007829|PDB:3KNV" FT HELIX 87..89 FT /evidence="ECO:0007829|PDB:3KNV" FT HELIX 94..101 FT /evidence="ECO:0007829|PDB:3KNV" FT STRAND 103..106 FT /evidence="ECO:0007829|PDB:3KNV" FT STRAND 115..117 FT /evidence="ECO:0007829|PDB:3KNV" FT HELIX 118..124 FT /evidence="ECO:0007829|PDB:3KNV" FT TURN 125..127 FT /evidence="ECO:0007829|PDB:3KNV" FT HELIX 130..133 FT /evidence="ECO:0007829|PDB:3KNV" FT HELIX 315..318 FT /evidence="ECO:0007829|PDB:1CA9" FT HELIX 335..347 FT /evidence="ECO:0007829|PDB:1CZY" FT STRAND 350..358 FT /evidence="ECO:0007829|PDB:1CZY" FT HELIX 361..369 FT /evidence="ECO:0007829|PDB:1CZY" FT STRAND 375..377 FT /evidence="ECO:0007829|PDB:1D0J" FT STRAND 381..384 FT /evidence="ECO:0007829|PDB:1CZY" FT STRAND 389..395 FT /evidence="ECO:0007829|PDB:1CZY" FT HELIX 400..402 FT /evidence="ECO:0007829|PDB:1CZY" FT TURN 403..405 FT /evidence="ECO:0007829|PDB:1CZY" FT STRAND 406..414 FT /evidence="ECO:0007829|PDB:1CZY" FT HELIX 419..421 FT /evidence="ECO:0007829|PDB:1CZY" FT STRAND 430..434 FT /evidence="ECO:0007829|PDB:1CZY" FT STRAND 443..447 FT /evidence="ECO:0007829|PDB:1CZY" FT HELIX 454..456 FT /evidence="ECO:0007829|PDB:1CZY" FT STRAND 460..463 FT /evidence="ECO:0007829|PDB:1CZY" FT STRAND 467..474 FT /evidence="ECO:0007829|PDB:1CZY" FT HELIX 476..480 FT /evidence="ECO:0007829|PDB:1CZY" FT TURN 482..484 FT /evidence="ECO:0007829|PDB:1CZY" FT STRAND 490..496 FT /evidence="ECO:0007829|PDB:1CZY" SQ SEQUENCE 501 AA; 55859 MW; C508BE185B783B20 CRC64; MAAASVTPPG SLELLQPGFS KTLLGTKLEA KYLCSACRNV LRRPFQAQCG HRYCSFCLAS ILSSGPQNCA ACVHEGIYEE GISILESSSA FPDNAARREV ESLPAVCPSD GCTWKGTLKE YESCHEGRCP LMLTECPACK GLVRLGEKER HLEHECPERS LSCRHCRAPC CGADVKAHHE VCPKFPLTCD GCGKKKIPRE KFQDHVKTCG KCRVPCRFHA IGCLETVEGE KQQEHEVQWL REHLAMLLSS VLEAKPLLGD QSHAGSELLQ RCESLEKKTA TFENIVCVLN REVERVAMTA EACSRQHRLD QDKIEALSSK VQQLERSIGL KDLAMADLEQ KVLEMEASTY DGVFIWKISD FARKRQEAVA GRIPAIFSPA FYTSRYGYKM CLRIYLNGDG TGRGTHLSLF FVVMKGPNDA LLRWPFNQKV TLMLLDQNNR EHVIDAFRPD VTSSSFQRPV NDMNIASGCP LFCPVSKMEA KNSYVRDDAI FIKAIVDLTG L //