TRAF2_HUMAN
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 03-AUG-2022, entry version 247.
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>3.0.co;2-g;
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 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 [65]
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 [66]
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 [67]
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 [68]
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 [69]
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 [70]
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 [71]
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 [72]
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 [73]
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 [74]
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 [75]
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. Required
CC for normal antibody isotype switching from IgM to IgG. Has E3
CC ubiquitin-protein ligase activity and promotes 'Lys-63'-linked
CC ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is
CC an essential constituent of several E3 ubiquitin-protein ligase
CC complexes, where it promotes the ubiquitination of target proteins by
CC bringing them into contact with other E3 ubiquitin ligases. Regulates
CC BIRC2 and BIRC3 protein levels by inhibiting their autoubiquitination
CC and subsequent degradation; this does not depend on the TRAF2 RING-type
CC zinc finger domain. Plays a role in mediating activation of NF-kappa-B
CC by EIF2AK2/PKR. In complex with BIRC2 or BIRC3, promotes ubiquitination
CC of IKBKE. {ECO:0000269|PubMed:10346818, ECO:0000269|PubMed:11784851,
CC ECO:0000269|PubMed:11907583, ECO:0000269|PubMed:12917689,
CC ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15383523,
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:19937093,
CC ECO:0000269|PubMed:20047764, ECO:0000269|PubMed:20064526,
CC ECO:0000269|PubMed:20385093, ECO:0000269|PubMed:20577214,
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; 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; A0A0A0MR97: BAZ2B; NbExp=3; IntAct=EBI-355744, EBI-11985607;
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; F6RF56: CCNJL; NbExp=3; IntAct=EBI-355744, EBI-10177725;
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; 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; Q7L5A3: FAM214B; NbExp=3; IntAct=EBI-355744, EBI-745689;
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; Q7Z5V6-2: PPP1R32; NbExp=3; IntAct=EBI-355744, EBI-12000762;
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; 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).
CC {ECO:0000269|PubMed:19150425, 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/";
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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. [Q12933-1]
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 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 AlphaFoldDB; Q12933; -.
DR SMR; Q12933; -.
DR BioGRID; 113038; 569.
DR CORUM; Q12933; -.
DR DIP; DIP-6223N; -.
DR ELM; Q12933; -.
DR IntAct; Q12933; 444.
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; Q12933; -.
DR PeptideAtlas; Q12933; -.
DR PRIDE; Q12933; -.
DR ProteomicsDB; 59035; -. [Q12933-1]
DR ProteomicsDB; 59036; -. [Q12933-2]
DR ProteomicsDB; 59037; -. [Q12933-3]
DR ProteomicsDB; 59038; -. [Q12933-4]
DR Antibodypedia; 2422; 766 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 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; RHAEQEC; -.
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 NFkappaB 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 SignaLink; Q12933; -.
DR SIGNOR; Q12933; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 7186; 164 hits in 1125 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 121 other tissues.
DR ExpressionAtlas; Q12933; baseline and differential.
DR Genevisible; Q12933; HS.
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: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: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; IPI:UniProtKB.
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: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:1901215; P:negative regulation of neuron death; TAS:ParkinsonsUK-UCL.
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:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:1903721; P:positive regulation of I-kappaB phosphorylation; IEA:Ensembl.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IMP:UniProtKB.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IBA:GO_Central.
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:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0002637; P:regulation of immunoglobulin production; 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 Gene3D; 2.60.210.10; -; 1.
DR Gene3D; 3.30.40.10; -; 3.
DR InterPro; IPR002083; MATH/TRAF_dom.
DR InterPro; IPR043211; TNF_rcpt-assoc_TRAF.
DR InterPro; IPR012227; TNF_rcpt-assoc_TRAF_met.
DR InterPro; IPR008974; TRAF-like.
DR InterPro; IPR027133; TRAF2.
DR InterPro; IPR037305; TRAF2_MATH.
DR InterPro; IPR032070; TRAF_BIRC3-bd.
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; PTHR10131; 1.
DR PANTHER; PTHR10131:SF21; PTHR10131:SF21; 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 PROSITE; PS50144; MATH; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
DR PROSITE; PS50145; ZF_TRAF; 2.
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 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
