TRAF3_HUMAN
ID TRAF3_HUMAN Reviewed; 568 AA.
AC Q13114; B7Z8C4; Q12990; Q13076; Q13947; Q6AZX1; Q9UNL1;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 235.
DE RecName: Full=TNF receptor-associated factor 3 {ECO:0000312|HGNC:HGNC:12033};
DE EC=2.3.2.27 {ECO:0000269|PubMed:25847972};
DE AltName: Full=CD40 receptor-associated factor 1 {ECO:0000303|PubMed:7533327};
DE Short=CRAF1 {ECO:0000303|PubMed:7533327};
DE AltName: Full=CD40-binding protein {ECO:0000303|PubMed:7527023};
DE Short=CD40BP {ECO:0000303|PubMed:7527023};
DE AltName: Full=LMP1-associated protein 1 {ECO:0000303|PubMed:7859281};
DE Short=LAP1 {ECO:0000303|PubMed:7859281};
DE AltName: Full=RING-type E3 ubiquitin transferase TRAF3 {ECO:0000305};
GN Name=TRAF3 {ECO:0000312|HGNC:HGNC:12033};
GN Synonyms=CAP-1 {ECO:0000312|HGNC:HGNC:12033},
GN CRAF1 {ECO:0000303|PubMed:7533327}, TRAFAMN {ECO:0000250|UniProtKB:Q60803};
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 TNFRSF5.
RX PubMed=7527023; DOI=10.1016/s0021-9258(18)43772-6;
RA Hu H.M., O'Rourke K., Boguski M.S., Dixit V.M.;
RT "A novel RING finger protein interacts with the cytoplasmic domain of
RT CD40.";
RL J. Biol. Chem. 269:30069-30072(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, AND INTERACTION
RP WITH EBV LMP1.
RC TISSUE=Lymphoma;
RX PubMed=7859281; DOI=10.1016/0092-8674(95)90489-1;
RA Mosialos G., Birkenbach M., Yalamanchili R., VanArsdale T., Ware C.,
RA Kieff E.;
RT "The Epstein-Barr virus transforming protein LMP1 engages signaling
RT proteins for the tumor necrosis factor receptor family.";
RL Cell 80:389-399(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH TNFRSF5, AND
RP VARIANT THR-129.
RC TISSUE=Fetal brain;
RX PubMed=7530216; DOI=10.1016/0014-5793(94)01406-q;
RA Sato T., Irie S., Reed J.C.;
RT "A novel member of the TRAF family of putative signal transducing proteins
RT binds to the cytosolic domain of CD40.";
RL FEBS Lett. 358:113-118(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH TNFRSF5, AND
RP VARIANT THR-129.
RX PubMed=7533327; DOI=10.1126/science.7533327;
RA Cheng G., Cleary A.M., Ye Z.S., Hong D.I., Lederman S., Baltimore D.;
RT "Involvement of CRAF1, a relative of TRAF, in CD40 signaling.";
RL Science 267:1494-1498(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Thymus;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 536-568.
RX PubMed=10199393; DOI=10.1016/s0161-5890(98)00099-6;
RA van Eyndhoven W.G., Frank D., Kalachikov S., Cleary A.M., Hong D.I.,
RA Cho E., Nasr S., Perez A.J., Mackus W.J.M., Cayanis E., Wellington S.,
RA Fischer S.G., Warburton D., Lederman S.;
RT "A single gene for human TRAF-3 at chromosome 14q32.3 encodes a variety of
RT mRNA species by alternative polyadenylation, mRNA splicing and
RT transcription initiation.";
RL Mol. Immunol. 35:1189-1206(1998).
RN [10]
RP INTERACTION WITH LTBR.
RX PubMed=8663299; DOI=10.1074/jbc.271.25.14661;
RA Nakano H., Oshima H., Chung W., Williams-Abbott L., Ware C.F., Yagita H.,
RA Okumura K.;
RT "TRAF5, an activator of NF-kappaB and putative signal transducer for the
RT lymphotoxin-beta receptor.";
RL J. Biol. Chem. 271:14661-14664(1996).
RN [11]
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 [12]
RP INTERACTION WITH TNFRSF8.
RX PubMed=9168896; DOI=10.1006/bbrc.1997.6509;
RA Boucher L.-M., Marengere L.E., Lu Y., Thukral S., Mak T.W.;
RT "Binding sites of cytoplasmic effectors TRAF1, 2, and 3 on CD30 and other
RT members of the TNF receptor superfamily.";
RL Biochem. Biophys. Res. Commun. 233:592-600(1997).
RN [13]
RP INTERACTION WITH TNFRSF14.
RX PubMed=9162022; DOI=10.1074/jbc.272.22.14029;
RA Marsters S.A., Ayres T.M., Skubatch M., Gray C.L., Rothe M., Ashkenazi A.;
RT "Herpesvirus entry mediator, a member of the tumor necrosis factor receptor
RT (TNFR) family, interacts with members of the TNFR-associated factor family
RT and activates the transcription factors NF-kappaB and AP-1.";
RL J. Biol. Chem. 272:14029-14032(1997).
RN [14]
RP INTERACTION WITH MAP3K14.
RX PubMed=9275204; DOI=10.1073/pnas.94.18.9792;
RA Song H.Y., Regnier C.H., Kirschning C.J., Goeddel D.V., Rothe M.;
RT "Tumor necrosis factor (TNF)-mediated kinase cascades: bifurcation of
RT nuclear factor-kappaB and c-jun N-terminal kinase (JNK/SAPK) pathways at
RT TNF receptor-associated factor 2.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:9792-9796(1997).
RN [15]
RP INTERACTION WITH TNFRSF5 AND TRAF5.
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
RP INTERACTION WITH MAP3K5.
RX PubMed=10523862; DOI=10.1038/sj.onc.1202975;
RA Hoeflich K.P., Yeh W.C., Yao Z., Mak T.W., Woodgett J.R.;
RT "Mediation of TNF receptor-associated factor effector functions by
RT apoptosis signal-regulating kinase-1 (ASK1).";
RL Oncogene 18:5814-5820(1999).
RN [22]
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 [23]
RP INTERACTION WITH TTRAP.
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 [24]
RP INTERACTION WITH TRAF3IP1.
RX PubMed=10791955; DOI=10.1074/jbc.m001095200;
RA Ling L., Goeddel D.V.;
RT "MIP-T3, a novel protein linking tumor necrosis factor receptor-associated
RT factor 3 to the microtubule network.";
RL J. Biol. Chem. 275:23852-23860(2000).
RN [25]
RP INTERACTION WITH TNFRSF17.
RX PubMed=10903733; DOI=10.4049/jimmunol.165.3.1322;
RA Hatzoglou A., Roussel J., Bourgeade M.-F., Rogier E., Madry C., Inoue J.,
RA Devergne O., Tsapis A.;
RT "TNF receptor family member BCMA (B cell maturation) associates with TNF
RT receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-
RT kappa B, elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein
RT kinase.";
RL J. Immunol. 165:1322-1330(2000).
RN [26]
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 [27]
RP FUNCTION, SUBCELLULAR LOCATION, 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 [28]
RP FUNCTION, PROTEASOMAL DEGRADATION, AND INTERACTION WITH MAP3K14.
RX PubMed=15084608; DOI=10.1074/jbc.m403286200;
RA Liao G., Zhang M., Harhaj E.W., Sun S.C.;
RT "Regulation of the NF-kappaB-inducing kinase by tumor necrosis factor
RT receptor-associated factor 3-induced degradation.";
RL J. Biol. Chem. 279:26243-26250(2004).
RN [29]
RP INTERACTION WITH OTUD5 AND TBK1, FUNCTION AS E3 PROTEIN-UBIQUITIN LIGASE,
RP AND UBIQUITINATION.
RX PubMed=17991829; DOI=10.1126/science.1145918;
RA Kayagaki N., Phung Q., Chan S., Chaudhari R., Quan C., O'Rourke K.M.,
RA Eby M., Pietras E., Cheng G., Bazan J.F., Zhang Z., Arnott D., Dixit V.M.;
RT "DUBA: a deubiquitinase that regulates type I interferon production.";
RL Science 318:1628-1632(2007).
RN [30]
RP INTERACTION WITH NEW YORK HANTAVIRUS GLYCOPROTEIN N (MICROBIAL INFECTION).
RX PubMed=18614628; DOI=10.1128/jvi.00290-08;
RA Alff P.J., Sen N., Gorbunova E., Gavrilovskaya I.N., Mackow E.R.;
RT "The NY-1 hantavirus Gn cytoplasmic tail coprecipitates TRAF3 and inhibits
RT cellular interferon responses by disrupting TBK1-TRAF3 complex formation.";
RL J. Virol. 82:9115-9122(2008).
RN [31]
RP INTERACTION WITH SRC.
RX PubMed=19419966; DOI=10.1074/jbc.m808233200;
RA Johnsen I.B., Nguyen T.T., Bergstroem B., Fitzgerald K.A., Anthonsen M.W.;
RT "The tyrosine kinase c-Src enhances RIG-I (retinoic acid-inducible gene I)-
RT elicited antiviral signaling.";
RL J. Biol. Chem. 284:19122-19131(2009).
RN [32]
RP UBIQUITINATION, MUTAGENESIS OF TYR-441 AND GLN-443, AND INTERACTION WITH
RP RNF216 AND MAVS.
RX PubMed=19893624; DOI=10.1371/journal.ppat.1000650;
RA Nakhaei P., Mesplede T., Solis M., Sun Q., Zhao T., Yang L., Chuang T.H.,
RA Ware C.F., Lin R., Hiscott J.;
RT "The E3 ubiquitin ligase Triad3A negatively regulates the RIG-I/MAVS
RT signaling pathway by targeting TRAF3 for degradation.";
RL PLoS Pathog. 5:E1000650-E1000650(2009).
RN [33]
RP UBIQUITINATION, AND INTERACTION WITH OTUB1 AND OTUB2.
RX PubMed=19996094; DOI=10.1074/jbc.m109.074971;
RA Li S., Zheng H., Mao A.P., Zhong B., Li Y., Liu Y., Gao Y., Ran Y.,
RA Tien P., Shu H.B.;
RT "Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated
RT deubiquitination of TRAF3 and TRAF6.";
RL J. Biol. Chem. 285:4291-4297(2010).
RN [34]
RP FUNCTION, INTERACTION WITH BIRC2 AND BIRC3, SUBCELLULAR LOCATION, AND
RP UBIQUITINATION.
RX PubMed=20097753; DOI=10.1074/jbc.m109.071043;
RA Mao A.P., Li S., Zhong B., Li Y., Yan J., Li Q., Teng C., Shu H.B.;
RT "Virus-triggered ubiquitination of TRAF3/6 by cIAP1/2 is essential for
RT induction of interferon-beta (IFN-beta) and cellular antiviral response.";
RL J. Biol. Chem. 285:9470-9476(2010).
RN [35]
RP FUNCTION.
RX PubMed=20185819; DOI=10.1074/jbc.m109.076091;
RA Bista P., Zeng W., Ryan S., Bailly V., Browning J.L., Lukashev M.E.;
RT "TRAF3 controls activation of the canonical and alternative NFkappaB by the
RT lymphotoxin beta receptor.";
RL J. Biol. Chem. 285:12971-12978(2010).
RN [36]
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 [37]
RP INTERACTION WITH OPTN AND TBK1.
RX PubMed=20174559; DOI=10.1371/journal.ppat.1000778;
RA Mankouri J., Fragkoudis R., Richards K.H., Wetherill L.F., Harris M.,
RA Kohl A., Elliott R.M., Macdonald A.;
RT "Optineurin negatively regulates the induction of IFNbeta in response to
RT RNA virus infection.";
RL PLoS Pathog. 6:E1000778-E1000778(2010).
RN [38]
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 [39]
RP INTERACTION WITH PTPN22.
RX PubMed=23871208; DOI=10.1016/j.immuni.2013.06.013;
RA Wang Y., Shaked I., Stanford S.M., Zhou W., Curtsinger J.M., Mikulski Z.,
RA Shaheen Z.R., Cheng G., Sawatzke K., Campbell A.M., Auger J.L., Bilgic H.,
RA Shoyama F.M., Schmeling D.O., Balfour H.H. Jr., Hasegawa K., Chan A.C.,
RA Corbett J.A., Binstadt B.A., Mescher M.F., Ley K., Bottini N.,
RA Peterson E.J.;
RT "The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-
RT driven, type 1 interferon-dependent immunity.";
RL Immunity 39:111-122(2013).
RN [40]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [41]
RP INTERACTION WITH NEW YORK HANTAVIRUS GLYCOPROTEIN N (MICROBIAL INFECTION),
RP INTERACTION WITH ANDES HANTAVIRUS GLYCOPROTEIN N (MICROBIAL INFECTION), AND
RP INTERACTION WITH TULA HANTAVIRUS GLYCOPROTEIN N (MICROBIAL INFECTION).
RX PubMed=24390324; DOI=10.1128/jvi.02647-13;
RA Matthys V.S., Cimica V., Dalrymple N.A., Glennon N.B., Bianco C.,
RA Mackow E.R.;
RT "Hantavirus GnT elements mediate TRAF3 binding and inhibit RIG-I/TBK1-
RT directed beta interferon transcription by blocking IRF3 phosphorylation.";
RL J. Virol. 88:2246-2259(2014).
RN [42]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP CYS-68 AND HIS-70.
RX PubMed=25847972; DOI=10.4049/jimmunol.1402851;
RA Guan K., Wei C., Zheng Z., Song T., Wu F., Zhang Y., Cao Y., Ma S.,
RA Chen W., Xu Q., Xia W., Gu J., He X., Zhong H.;
RT "MAVS Promotes Inflammasome Activation by Targeting ASC for K63-Linked
RT Ubiquitination via the E3 Ligase TRAF3.";
RL J. Immunol. 194:4880-4890(2015).
RN [43]
RP INTERACTION WITH GAPDH.
RX PubMed=27387501; DOI=10.1074/jbc.m116.738278;
RA Gao X., Pham T.H., Feuerbacher L.A., Chen K., Hays M.P., Singh G.,
RA Rueter C., Hurtado-Guerrero R., Hardwidge P.R.;
RT "Citrobacter rodentium NleB protein inhibits tumor necrosis factor (TNF)
RT receptor-associated factor 3 (TRAF3) ubiquitination to reduce host type I
RT interferon production.";
RL J. Biol. Chem. 291:18232-18238(2016).
RN [44]
RP FUNCTION, UBIQUITINATION AT LYS-168, MUTAGENESIS OF LYS-168, AND
RP INTERACTION WITH RALGDS.
RX PubMed=27438768; DOI=10.1016/j.immuni.2016.06.023;
RA Miao Y., Wu J., Abraham S.N.;
RT "Ubiquitination of Innate Immune Regulator TRAF3 Orchestrates Expulsion of
RT Intracellular Bacteria by Exocyst Complex.";
RL Immunity 45:94-105(2016).
RN [45]
RP INTERACTION WITH DDX3X; IKBKE; IRF3 AND MAVS, UBIQUITINATION, AND
RP MUTAGENESIS OF 68-CYS--HIS-70.
RX PubMed=27980081; DOI=10.1042/bcj20160956;
RA Gu L., Fullam A., McCormack N., Hoehn Y., Schroeder M.;
RT "DDX3 directly regulates TRAF3 ubiquitination and acts as a scaffold to co-
RT ordinate assembly of signalling complexes downstream from MAVS.";
RL Biochem. J. 474:571-587(2017).
RN [46]
RP FUNCTION, INTERACTION WITH TRIM35, SUBCELLULAR LOCATION, AND
RP UBIQUITINATION.
RX PubMed=32562145; DOI=10.1007/s13238-020-00734-6;
RA Sun N., Jiang L., Ye M., Wang Y., Wang G., Wan X., Zhao Y., Wen X.,
RA Liang L., Ma S., Liu L., Bu Z., Chen H., Li C.;
RT "TRIM35 mediates protection against influenza infection by activating TRAF3
RT and degrading viral PB2.";
RL Protein Cell 11:894-914(2020).
RN [47]
RP FUNCTION, CLEAVAGE BY ENTEROVIRUS D68 PROTEASE 2A (MICROBIAL INFECTION),
RP AND MUTAGENESIS OF GLY-462.
RX PubMed=33148796; DOI=10.1128/jvi.01856-20;
RA Kang J., Pang Z., Zhou Z., Li X., Liu S., Cheng J., Liu P., Tan W.,
RA Wang Z., Wang T.;
RT "Enterovirus D68 Protease 2Apro Targets TRAF3 To Subvert Host Innate Immune
RT Responses.";
RL J. Virol. 95:0-0(2021).
RN [48]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ATP1B1, AND
RP UBIQUITINATION.
RX PubMed=34011520; DOI=10.4049/jimmunol.2001262;
RA Cao W., Guo Y., Cheng Z., Xu G., Zuo Q., Nie L., Huang Y., Liu S., Zhu Y.;
RT "Inducible ATP1B1 Upregulates Antiviral Innate Immune Responses by the
RT Ubiquitination of TRAF3 and TRAF6.";
RL J. Immunol. 206:2668-2681(2021).
RN [49]
RP FUNCTION, UBIQUITINATION AT CYS-56 AND CYS-124 BY NEDD4L, AND MUTAGENESIS
RP OF CYS-56 AND CYS-124.
RX PubMed=33608556; DOI=10.1038/s41467-021-21456-1;
RA Gao P., Ma X., Yuan M., Yi Y., Liu G., Wen M., Jiang W., Ji R., Zhu L.,
RA Tang Z., Yu Q., Xu J., Yang R., Xia S., Yang M., Pan J., Yuan H., An H.;
RT "E3 ligase Nedd4l promotes antiviral innate immunity by catalyzing K29-
RT linked cysteine ubiquitination of TRAF3.";
RL Nat. Commun. 12:1194-1194(2021).
RN [50]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 341-568, AND X-RAY CRYSTALLOGRAPHY
RP (3.5 ANGSTROMS) OF 341-568 IN COMPLEX WITH TNFRSF5.
RX PubMed=10984535; DOI=10.1073/pnas.97.19.10395;
RA Ni C.Z., Welsh K., Leo E., Chiou C.K., Wu H., Reed J.C., Ely K.R.;
RT "Molecular basis for CD40 signaling mediated by TRAF3.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:10395-10399(2000).
RN [51]
RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 377-568 IN COMPLEX WITH TANK, AND
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 377-568 IN COMPLEX WITH TNFRSF5.
RX PubMed=12005438; DOI=10.1016/s0969-2126(02)00733-5;
RA Li C., Ni C.Z., Havert M.L., Cabezas E., He J., Kaiser D., Reed J.C.,
RA Satterthwait A.C., Cheng G., Ely K.R.;
RT "Downstream regulator TANK binds to the CD40 recognition site on TRAF3.";
RL Structure 10:403-411(2002).
RN [52]
RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 377-568 IN COMPLEX WITH LTBR,
RP MUTAGENESIS OF TYR-459; PHE-512 AND PHE-521, INTERACTION WITH TANK AND
RP CD40, AND SUBUNIT.
RX PubMed=14517219; DOI=10.1074/jbc.m309381200;
RA Li C., Norris P.S., Ni C.Z., Havert M.L., Chiong E.M., Tran B.R.,
RA Cabezas E., Reed J.C., Satterthwait A.C., Ware C.F., Ely K.R.;
RT "Structurally distinct recognition motifs in lymphotoxin-beta receptor and
RT CD40 for tumor necrosis factor receptor-associated factor (TRAF)-mediated
RT signaling.";
RL J. Biol. Chem. 278:50523-50529(2003).
RN [53]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 377-568 IN COMPLEX WITH TNFRSF13C
RP PEPTIDE, SUBUNIT, AND INTERACTION WITH TNFRSF13C.
RX PubMed=15585864; DOI=10.4049/jimmunol.173.12.7394;
RA Ni C.Z., Oganesyan G., Welsh K., Zhu X., Reed J.C., Satterthwait A.C.,
RA Cheng G., Ely K.R.;
RT "Key molecular contacts promote recognition of the BAFF receptor by TNF
RT receptor-associated factor 3: implications for intracellular signaling
RT regulation.";
RL J. Immunol. 173:7394-7400(2004).
RN [54]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 377-568 IN COMPLEX WITH
RP EPSTEIN-BARR VIRUS PROTEIN LMP1 (MICROBIAL INFECTION), AND SUBUNIT.
RX PubMed=16009714; DOI=10.1074/jbc.m502511200;
RA Wu S., Xie P., Welsh K., Li C., Ni C.Z., Zhu X., Reed J.C.,
RA Satterthwait A.C., Bishop G.A., Ely K.R.;
RT "LMP1 protein from the Epstein-Barr virus is a structural CD40 decoy in B
RT lymphocytes for binding to TRAF3.";
RL J. Biol. Chem. 280:33620-33626(2005).
RN [55]
RP STRUCTURE BY NMR OF 43-101.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the zinc finger, C3HC4 type (RING finger) domain of
RT TNF receptor-associated factor 3.";
RL Submitted (FEB-2008) to the PDB data bank.
RN [56]
RP VARIANT IIAE5 TRP-118.
RX PubMed=20832341; DOI=10.1016/j.immuni.2010.08.014;
RA Perez de Diego R., Sancho-Shimizu V., Lorenzo L., Puel A., Plancoulaine S.,
RA Picard C., Herman M., Cardon A., Durandy A., Bustamante J.,
RA Vallabhapurapu S., Bravo J., Warnatz K., Chaix Y., Cascarrigny F.,
RA Lebon P., Rozenberg F., Karin M., Tardieu M., Al-Muhsen S., Jouanguy E.,
RA Zhang S.Y., Abel L., Casanova J.L.;
RT "Human TRAF3 adaptor molecule deficiency leads to impaired Toll-like
RT receptor 3 response and susceptibility to herpes simplex encephalitis.";
RL Immunity 33:400-411(2010).
CC -!- FUNCTION: Cytoplasmic E3 ubiquitin ligase that regulates various
CC signaling pathways, such as the NF-kappa-B, mitogen-activated protein
CC kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus
CC controls a lot of biological processes in both immune and non-immune
CC cell types (PubMed:33148796, PubMed:33608556). In TLR and RLR signaling
CC pathways, acts as an E3 ubiquitin ligase promoting the synthesis of
CC 'Lys-63'-linked polyubiquitin chains on several substrates such as ASC
CC that lead to the activation of the type I interferon response or the
CC inflammasome (PubMed:25847972, PubMed:27980081). Following the
CC activation of certain TLRs such as TLR4, acts as a negative NF-kappa-B
CC regulator, possibly to avoid unregulated inflammatory response, and its
CC degradation via 'Lys-48'-linked polyubiquitination is required for MAPK
CC activation and production of inflammatory cytokines. Alternatively,
CC when TLR4 orchestrates bacterial expulsion, TRAF3 undergoes 'Lys-33'-
CC linked polyubiquitination and subsequently binds to RALGDS, mobilizing
CC the exocyst complex to rapidly expel intracellular bacteria back for
CC clearance (PubMed:27438768). Acts also as a constitutive negative
CC regulator of the alternative NF-kappa-B pathway, which controls B-cell
CC survival and lymphoid organ development. Required for normal antibody
CC isotype switching from IgM to IgG. Plays a role T-cell dependent immune
CC responses. Down-regulates proteolytic processing of NFKB2, and thereby
CC inhibits non-canonical activation of NF-kappa-B. Promotes
CC ubiquitination and proteasomal degradation of MAP3K14.
CC {ECO:0000269|PubMed:15084608, ECO:0000269|PubMed:15383523,
CC ECO:0000269|PubMed:17991829, ECO:0000269|PubMed:19937093,
CC ECO:0000269|PubMed:20097753, ECO:0000269|PubMed:20185819,
CC ECO:0000269|PubMed:25847972, ECO:0000269|PubMed:27980081,
CC ECO:0000269|PubMed:32562145, ECO:0000269|PubMed:33148796,
CC ECO:0000269|PubMed:33608556, ECO:0000269|PubMed:34011520}.
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; Evidence={ECO:0000269|PubMed:25847972};
CC -!- SUBUNIT: Homotrimer. Heterotrimer with TRAF2 and TRAF5. Interacts with
CC LTBR/TNFRSF3, TNFRSF4, TNFRSF5/CD40, TNFRSF8/CD30, TNFRSF13C
CC TNFRSF17/BCMA, TLR4 and EDAR. Interacts with MAP3K5, MAP3K14,
CC TRAIP/TRIP, TDP2/TTRAP, TANK/ITRAF and TRAF3IP1. Interaction with
CC TNFRSF5/CD40 is modulated by TANK/ITRAF, which competes for the same
CC binding site. Interacts with TICAM1. Interacts with TRAFD1. Interacts
CC with OTUB1, OTUB2 and OTUD5. Interacts with RNF216, OPTN and TBK1.
CC Identified in a complex with TRAF2, MAP3K14 and BIRC3. Interacts with
CC BIRC2 and BIRC3. Upon exposure to bacterial lipopolysaccharide (LPS),
CC recruited to a transient complex containing TLR4, TRAF3, TRAF6, IKBKG,
CC MAP3K7, MYD88, TICAM1, BIRC2, BIRC3 and UBE2N (By similarity).
CC Interacts (via RING-type zinc finger domain) with SRC. Interacts with
CC CARD14. Interacts (via MATH domain) with PTPN22; the interaction
CC promotes TRAF3 polyubiquitination (PubMed:23871208). Interacts with
CC MAVS (PubMed:19893624, PubMed:27980081). Directly interacts with DDX3X;
CC this interaction stimulates TRAF3 'Lys-63' ubiquitination
CC (PubMed:27980081). Interacts with IRF3 (PubMed:27980081). Interacts
CC with IKBKE in the course of Sendai virus infection (PubMed:27980081).
CC Interacts with TRIM35 (PubMed:32562145). Interacts with GAPDH;
CC promoting TRAF3 ubiquitination (PubMed:27387501). Interacts with PPP3CA
CC and PPP3CB (By similarity). Interacts with ATP1B1; promoting TRAF3
CC ubiquitination (PubMed:27387501). Interacts with RALGDS
CC (PubMed:27438768). {ECO:0000250|UniProtKB:Q60803,
CC ECO:0000269|PubMed:10037686, ECO:0000269|PubMed:10523862,
CC ECO:0000269|PubMed:10764746, ECO:0000269|PubMed:10791955,
CC ECO:0000269|PubMed:10809768, ECO:0000269|PubMed:10903733,
CC ECO:0000269|PubMed:10984535, ECO:0000269|PubMed:11035039,
CC ECO:0000269|PubMed:12005438, ECO:0000269|PubMed:14517219,
CC ECO:0000269|PubMed:15084608, ECO:0000269|PubMed:15383523,
CC ECO:0000269|PubMed:15585864, ECO:0000269|PubMed:16009714,
CC ECO:0000269|PubMed:17991829, ECO:0000269|PubMed:19419966,
CC ECO:0000269|PubMed:19893624, ECO:0000269|PubMed:19996094,
CC ECO:0000269|PubMed:20097753, ECO:0000269|PubMed:20174559,
CC ECO:0000269|PubMed:21302310, ECO:0000269|PubMed:23871208,
CC ECO:0000269|PubMed:27387501, ECO:0000269|PubMed:27438768,
CC ECO:0000269|PubMed:27980081, ECO:0000269|PubMed:32562145,
CC ECO:0000269|PubMed:7527023, ECO:0000269|PubMed:7530216,
CC ECO:0000269|PubMed:7533327, ECO:0000269|PubMed:8663299,
CC ECO:0000269|PubMed:8710854, ECO:0000269|PubMed:9162022,
CC ECO:0000269|PubMed:9168896, ECO:0000269|PubMed:9275204,
CC ECO:0000269|PubMed:9418902, ECO:0000269|PubMed:9488716,
CC ECO:0000269|PubMed:9718306, ECO:0000269|PubMed:9774460,
CC ECO:0000269|PubMed:9774977}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via N-terminus) with New York
CC hantavirus glycoprotein N (via C-terminus); this interaction inhibits
CC the formation of TRAF3-TBK1 complexes. {ECO:0000269|PubMed:18614628,
CC ECO:0000269|PubMed:24390324}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Andes hantavirus
CC glycoprotein N (via C-terminus); this interaction inhibits the
CC formation of TRAF3-TBK1 complexes. {ECO:0000269|PubMed:24390324}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Tula hantavirus
CC glycoprotein N (via C-terminus); this interaction inhibits the
CC formation of TRAF3-TBK1 complexes. {ECO:0000269|PubMed:24390324}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus
CC protein LMP1. {ECO:0000269|PubMed:7859281}.
CC -!- INTERACTION:
CC Q13114; Q8N9N2-2: ASCC1; NbExp=3; IntAct=EBI-357631, EBI-10962548;
CC Q13114; Q86UB2: BIVM; NbExp=6; IntAct=EBI-357631, EBI-12191873;
CC Q13114; P15056: BRAF; NbExp=2; IntAct=EBI-357631, EBI-365980;
CC Q13114; Q5T681: C10orf62; NbExp=3; IntAct=EBI-357631, EBI-744052;
CC Q13114; Q8IYE1: CCDC13; NbExp=3; IntAct=EBI-357631, EBI-10961312;
CC Q13114; Q52MB2: CCDC184; NbExp=3; IntAct=EBI-357631, EBI-10179526;
CC Q13114; P25942: CD40; NbExp=3; IntAct=EBI-357631, EBI-525714;
CC Q13114; Q16543: CDC37; NbExp=3; IntAct=EBI-357631, EBI-295634;
CC Q13114; Q9HAV5: EDA2R; NbExp=2; IntAct=EBI-357631, EBI-526033;
CC Q13114; Q9Y692: GMEB1; NbExp=2; IntAct=EBI-357631, EBI-2339665;
CC Q13114; Q9UKD1: GMEB2; NbExp=3; IntAct=EBI-357631, EBI-948296;
CC Q13114; Q9Y547: HSPB11; NbExp=3; IntAct=EBI-357631, EBI-747101;
CC Q13114; Q96PC2: IP6K3; NbExp=5; IntAct=EBI-357631, EBI-10990676;
CC Q13114; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-357631, EBI-739832;
CC Q13114; P36941: LTBR; NbExp=2; IntAct=EBI-357631, EBI-3509981;
CC Q13114; Q99558: MAP3K14; NbExp=8; IntAct=EBI-357631, EBI-358011;
CC Q13114; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-357631, EBI-741158;
CC Q13114; Q17RL8: PDZD4; NbExp=3; IntAct=EBI-357631, EBI-10239064;
CC Q13114; O75928-2: PIAS2; NbExp=3; IntAct=EBI-357631, EBI-348567;
CC Q13114; Q96HA1-2: POM121; NbExp=3; IntAct=EBI-357631, EBI-11956563;
CC Q13114; P28062-2: PSMB8; NbExp=3; IntAct=EBI-357631, EBI-372312;
CC Q13114; Q9Y2R2: PTPN22; NbExp=2; IntAct=EBI-357631, EBI-1211241;
CC Q13114; P54725: RAD23A; NbExp=3; IntAct=EBI-357631, EBI-746453;
CC Q13114; Q13546: RIPK1; NbExp=3; IntAct=EBI-357631, EBI-358507;
CC Q13114; O43353: RIPK2; NbExp=6; IntAct=EBI-357631, EBI-358522;
CC Q13114; Q0D2K3: RIPPLY1; NbExp=3; IntAct=EBI-357631, EBI-10226430;
CC Q13114; P78317: RNF4; NbExp=3; IntAct=EBI-357631, EBI-2340927;
CC Q13114; O95721: SNAP29; NbExp=4; IntAct=EBI-357631, EBI-490676;
CC Q13114; Q92844: TANK; NbExp=7; IntAct=EBI-357631, EBI-356349;
CC Q13114; Q9UHD2: TBK1; NbExp=4; IntAct=EBI-357631, EBI-356402;
CC Q13114; Q13114: TRAF3; NbExp=5; IntAct=EBI-357631, EBI-357631;
CC Q13114; Q8TDR0: TRAF3IP1; NbExp=8; IntAct=EBI-357631, EBI-928811;
CC Q13114; O00463: TRAF5; NbExp=4; IntAct=EBI-357631, EBI-523498;
CC Q13114; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-357631, EBI-10180829;
CC Q13114; P61964: WDR5; NbExp=2; IntAct=EBI-357631, EBI-540834;
CC Q13114; Q6ZSB9: ZBTB49; NbExp=3; IntAct=EBI-357631, EBI-2859943;
CC Q13114; Q15326: ZMYND11; NbExp=2; IntAct=EBI-357631, EBI-2623509;
CC Q13114; Q8NAM6: ZSCAN4; NbExp=3; IntAct=EBI-357631, EBI-7252920;
CC Q13114; Q9QYP6: Azi2; Xeno; NbExp=2; IntAct=EBI-357631, EBI-6115874;
CC Q13114; P15314: Irf1; Xeno; NbExp=2; IntAct=EBI-357631, EBI-6115486;
CC Q13114; A2APF7: Zbp1; Xeno; NbExp=2; IntAct=EBI-357631, EBI-6115394;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25847972,
CC ECO:0000269|PubMed:34011520}. Endosome {ECO:0000250|UniProtKB:Q60803}.
CC Mitochondrion {ECO:0000269|PubMed:32562145}. Note=Undergoes endocytosis
CC together with TLR4 upon LPS signaling (By similarity). Co-localized to
CC mitochondria with TRIM35 (PubMed:32562145).
CC {ECO:0000250|UniProtKB:Q60803, ECO:0000269|PubMed:32562145}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13114-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13114-2; Sequence=VSP_040040;
CC -!- DOMAIN: The MATH/TRAF domain binds to receptor cytoplasmic domains.
CC -!- DOMAIN: The Ring-type zinc finger domain is required for its function
CC in down-regulation of NFKB2 proteolytic processing.
CC {ECO:0000250|UniProtKB:Q60803}.
CC -!- PTM: Undergoes 'Lys-48'-linked polyubiquitination, leading to its
CC proteasomal degradation in response to signaling by TNFSF13B, TLR4 or
CC through CD40. 'Lys-48'-linked polyubiquitinated form is deubiquitinated
CC by OTUD7B, preventing TRAF3 proteolysis and over-activation of non-
CC canonical NF-kappa-B. Undergoes 'Lys-63'-linked ubiquitination during
CC early stages of virus infection, and 'Lys-48'-linked ubiquitination
CC during later stages. Undergoes both 'Lys-48'-linked and 'Lys-63'-linked
CC ubiquitination in response to TLR3 and TLR4 signaling. 'Lys-63'-linked
CC ubiquitination can be mediated by TRIM35. Deubiquitinated by OTUB1,
CC OTUB2 and OTUD5. Undergoes 'Lys-63'-linked deubiquitination by MYSM1 to
CC terminate the pattern-recognition receptors/PRRs pathways (By
CC similarity). Undergoes also 'Lys-29'-linked ubiquitination on Cys-56
CC and Cys-124 by NEDD4L; leading to increased 'Lys-48'- and 'Lys-63'-
CC linked ubiquitination as well as increased binding to TBK1
CC (PubMed:33608556). TLR4 signals emanating from bacteria containing
CC vesicles trigger 'Lys-33'-linked polyubiquitination that promotes the
CC assembly of the exocyst complex thereby connecting innate immune
CC signaling to the cellular trafficking apparatus (PubMed:27438768).
CC Deubiquitinated by USP25 during viral infection, leading to TRAF3
CC stabilization and type I interferon production (By similarity).
CC {ECO:0000250|UniProtKB:Q60803, ECO:0000269|PubMed:17991829,
CC ECO:0000269|PubMed:19893624, ECO:0000269|PubMed:19937093,
CC ECO:0000269|PubMed:19996094, ECO:0000269|PubMed:20097753,
CC ECO:0000269|PubMed:27438768, ECO:0000269|PubMed:27980081,
CC ECO:0000269|PubMed:32562145, ECO:0000269|PubMed:33608556,
CC ECO:0000269|PubMed:34011520}.
CC -!- PTM: (Microbial infection) Cleaved by enterovirus D68 protease 2A;
CC leading to inhibition of NF-kappa-B or IFN-beta triggered by TRAF3.
CC {ECO:0000269|PubMed:33148796}.
CC -!- DISEASE: Encephalopathy, acute, infection-induced, 5, herpes-specific
CC (IIAE5) [MIM:614849]: A rare complication of human herpesvirus 1 (HHV-
CC 1) infection, occurring in only a small minority of HHV-1 infected
CC individuals. It is characterized by hemorrhagic necrosis of parts of
CC the temporal and frontal lobes. Onset is over several days and involves
CC fever, headache, seizures, stupor, and often coma, frequently with a
CC fatal outcome. {ECO:0000269|PubMed:20832341}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the TNF receptor-associated factor family. A
CC subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TRAF3ID271.html";
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DR EMBL; U15637; AAA56753.1; -; mRNA.
DR EMBL; U19260; AAA65732.1; -; mRNA.
DR EMBL; L38509; AAA68195.1; -; mRNA.
DR EMBL; U21092; AAC50112.1; -; mRNA.
DR EMBL; BX247977; CAD62311.1; -; mRNA.
DR EMBL; AK303172; BAH13910.1; -; mRNA.
DR EMBL; AL117209; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC075087; AAH75087.1; -; mRNA.
DR EMBL; BC075086; AAH75086.1; -; mRNA.
DR EMBL; AF110908; AAD29276.1; -; mRNA.
DR CCDS; CCDS55946.1; -. [Q13114-2]
DR CCDS; CCDS9975.1; -. [Q13114-1]
DR PIR; A55960; A55960.
DR PIR; S68467; S68467.
DR RefSeq; NP_001186356.1; NM_001199427.1. [Q13114-2]
DR RefSeq; NP_003291.2; NM_003300.3. [Q13114-1]
DR RefSeq; NP_663777.1; NM_145725.2. [Q13114-1]
DR RefSeq; NP_663778.1; NM_145726.2.
DR RefSeq; XP_011535420.1; XM_011537118.2. [Q13114-2]
DR RefSeq; XP_016877106.1; XM_017021617.1. [Q13114-1]
DR RefSeq; XP_016877107.1; XM_017021618.1. [Q13114-1]
DR PDB; 1FLK; X-ray; 2.80 A; A/B=341-568.
DR PDB; 1FLL; X-ray; 3.50 A; A/B=341-568.
DR PDB; 1KZZ; X-ray; 3.50 A; A=377-568.
DR PDB; 1L0A; X-ray; 2.90 A; A=377-568.
DR PDB; 1RF3; X-ray; 3.50 A; A=377-568.
DR PDB; 1ZMS; X-ray; 2.80 A; A=377-568.
DR PDB; 2ECY; NMR; -; A=43-101.
DR PDB; 2GKW; X-ray; 2.70 A; A=377-568.
DR PDBsum; 1FLK; -.
DR PDBsum; 1FLL; -.
DR PDBsum; 1KZZ; -.
DR PDBsum; 1L0A; -.
DR PDBsum; 1RF3; -.
DR PDBsum; 1ZMS; -.
DR PDBsum; 2ECY; -.
DR PDBsum; 2GKW; -.
DR AlphaFoldDB; Q13114; -.
DR BMRB; Q13114; -.
DR SMR; Q13114; -.
DR BioGRID; 113039; 183.
DR ComplexPortal; CPX-6018; STING-TRAF3-TBK1 complex.
DR ComplexPortal; CPX-6037; MAVS-TRAF3 E3 ubiquitin ligase complex.
DR CORUM; Q13114; -.
DR DIP; DIP-6222N; -.
DR IntAct; Q13114; 80.
DR MINT; Q13114; -.
DR STRING; 9606.ENSP00000454207; -.
DR MoonDB; Q13114; Predicted.
DR iPTMnet; Q13114; -.
DR PhosphoSitePlus; Q13114; -.
DR BioMuta; TRAF3; -.
DR DMDM; 116242824; -.
DR EPD; Q13114; -.
DR jPOST; Q13114; -.
DR MassIVE; Q13114; -.
DR MaxQB; Q13114; -.
DR PaxDb; Q13114; -.
DR PeptideAtlas; Q13114; -.
DR PRIDE; Q13114; -.
DR ProteomicsDB; 59165; -. [Q13114-1]
DR ProteomicsDB; 59166; -. [Q13114-2]
DR Antibodypedia; 129; 540 antibodies from 44 providers.
DR CPTC; Q13114; 3 antibodies.
DR DNASU; 7187; -.
DR Ensembl; ENST00000392745.8; ENSP00000376500.3; ENSG00000131323.16. [Q13114-1]
DR Ensembl; ENST00000539721.5; ENSP00000445998.1; ENSG00000131323.16. [Q13114-2]
DR Ensembl; ENST00000560371.5; ENSP00000454207.1; ENSG00000131323.16. [Q13114-1]
DR GeneID; 7187; -.
DR KEGG; hsa:7187; -.
DR MANE-Select; ENST00000392745.8; ENSP00000376500.3; NM_145725.3; NP_663777.1.
DR UCSC; uc001ymc.3; human. [Q13114-1]
DR CTD; 7187; -.
DR DisGeNET; 7187; -.
DR GeneCards; TRAF3; -.
DR HGNC; HGNC:12033; TRAF3.
DR HPA; ENSG00000131323; Low tissue specificity.
DR MalaCards; TRAF3; -.
DR MIM; 601896; gene.
DR MIM; 614849; phenotype.
DR neXtProt; NX_Q13114; -.
DR OpenTargets; ENSG00000131323; -.
DR Orphanet; 1930; Herpes simplex virus encephalitis.
DR PharmGKB; PA36710; -.
DR VEuPathDB; HostDB:ENSG00000131323; -.
DR eggNOG; KOG0297; Eukaryota.
DR GeneTree; ENSGT00940000160538; -.
DR HOGENOM; CLU_021061_4_1_1; -.
DR InParanoid; Q13114; -.
DR OMA; ETVCPSF; -.
DR OrthoDB; 918518at2759; -.
DR PhylomeDB; Q13114; -.
DR TreeFam; TF321154; -.
DR PathwayCommons; Q13114; -.
DR Reactome; R-HSA-5602571; TRAF3 deficiency - HSE.
DR Reactome; R-HSA-5668541; TNFR2 non-canonical NF-kB pathway.
DR Reactome; R-HSA-5676594; TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases.
DR Reactome; R-HSA-9013973; TICAM1-dependent activation of IRF3/IRF7.
DR Reactome; R-HSA-918233; TRAF3-dependent IRF activation pathway.
DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling.
DR Reactome; R-HSA-936964; Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR SignaLink; Q13114; -.
DR SIGNOR; Q13114; -.
DR BioGRID-ORCS; 7187; 35 hits in 1129 CRISPR screens.
DR ChiTaRS; TRAF3; human.
DR EvolutionaryTrace; Q13114; -.
DR GeneWiki; TRAF3; -.
DR GenomeRNAi; 7187; -.
DR Pharos; Q13114; Tbio.
DR PRO; PR:Q13114; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q13114; protein.
DR Bgee; ENSG00000131323; Expressed in cartilage tissue and 174 other tissues.
DR ExpressionAtlas; Q13114; baseline and differential.
DR Genevisible; Q13114; HS.
DR GO; GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:1902554; C:serine/threonine protein kinase complex; IC:ComplexPortal.
DR GO; GO:0000151; C:ubiquitin ligase complex; IC:ComplexPortal.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR GO; GO:0031996; F:thioesterase 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; TAS:Reactome.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0051607; P:defense response to virus; IC:ComplexPortal.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IBA:GO_Central.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IBA:GO_Central.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0001817; P:regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0050688; P:regulation of defense response to virus; ISS:UniProtKB.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0032648; P:regulation of interferon-beta production; ISS:UniProtKB.
DR GO; GO:0030162; P:regulation of proteolysis; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0008063; P:Toll signaling pathway; IEA:InterPro.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0060337; P:type I interferon signaling pathway; IC:ComplexPortal.
DR CDD; cd03777; MATH_TRAF3; 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; IPR027128; TRAF3.
DR InterPro; IPR037304; TRAF3_MATH.
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:SF76; PTHR10131:SF76; 1.
DR Pfam; PF02176; zf-TRAF; 1.
DR PIRSF; PIRSF015614; TRAF; 1.
DR SMART; SM00061; MATH; 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; Alternative splicing; Apoptosis; Coiled coil; Cytoplasm;
KW Disease variant; Endosome; Host-virus interaction; Immunity;
KW Isopeptide bond; Metal-binding; Mitochondrion; Phosphoprotein;
KW Reference proteome; Repeat; Thioester bond; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..568
FT /note="TNF receptor-associated factor 3"
FT /id="PRO_0000056401"
FT DOMAIN 415..560
FT /note="MATH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00129"
FT ZN_FING 68..77
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 135..190
FT /note="TRAF-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00207"
FT ZN_FING 191..249
FT /note="TRAF-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00207"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 392..415
FT /note="(Microbial infection) Interaction with glycoprotein
FT N of Andes and New York hantaviruses"
FT /evidence="ECO:0000269|PubMed:24390324"
FT COILED 267..338
FT /evidence="ECO:0000255"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 56
FT /note="Glycyl cysteine thioester (Cys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:33608556"
FT CROSSLNK 124
FT /note="Glycyl cysteine thioester (Cys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:33608556"
FT CROSSLNK 168
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:27438768"
FT VAR_SEQ 191..273
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_040040"
FT VARIANT 118
FT /note="R -> W (in IIAE5; dbSNP:rs143813189)"
FT /evidence="ECO:0000269|PubMed:20832341"
FT /id="VAR_069081"
FT VARIANT 129
FT /note="M -> T (in dbSNP:rs1131877)"
FT /evidence="ECO:0000269|PubMed:7530216,
FT ECO:0000269|PubMed:7533327"
FT /id="VAR_052149"
FT MUTAGEN 56
FT /note="C->A: Strong increase in both 'Lys-48' and 'Lys-63'-
FT linked ubiquitination."
FT /evidence="ECO:0000269|PubMed:33608556"
FT MUTAGEN 68..70
FT /note="CGH->AGA: Loss of ubiquitination activity, impaired
FT interaction with MAVS and IRF3. No effect on interaction
FT with IKBKE, nor with DDX3X."
FT /evidence="ECO:0000269|PubMed:27980081"
FT MUTAGEN 68
FT /note="C->A: Loss of ubiquitination activity on ASC; when
FT associated with A-70."
FT /evidence="ECO:0000269|PubMed:25847972"
FT MUTAGEN 70
FT /note="H->A: Loss of ubiquitination activity on ASC; when
FT associated with A-68."
FT /evidence="ECO:0000269|PubMed:25847972"
FT MUTAGEN 124
FT /note="C->A: Strong increase in both 'Lys-48' and 'Lys-63'-
FT linked ubiquitination."
FT /evidence="ECO:0000269|PubMed:33608556"
FT MUTAGEN 168
FT /note="K->R: Abolishes interaction with RALGDS."
FT /evidence="ECO:0000269|PubMed:27438768"
FT MUTAGEN 441
FT /note="Y->A: Abolishes interaction with RNF216; when
FT associated with A-443."
FT /evidence="ECO:0000269|PubMed:19893624"
FT MUTAGEN 443
FT /note="Q->A: Abolishes interaction with RNF216; when
FT associated with A-441."
FT /evidence="ECO:0000269|PubMed:19893624"
FT MUTAGEN 459
FT /note="Y->A: Abolishes interaction with LTBR, CD40 and
FT TANK."
FT /evidence="ECO:0000269|PubMed:14517219"
FT MUTAGEN 462
FT /note="G->A: Confers resistance to cleavage by enterovirus
FT D68 protease 2A."
FT /evidence="ECO:0000269|PubMed:33148796"
FT MUTAGEN 512
FT /note="F->E: Abolishes interaction with LTBR, CD40 and
FT TANK."
FT /evidence="ECO:0000269|PubMed:14517219"
FT MUTAGEN 521
FT /note="F->A: Abolishes interaction with LTBR, CD40 and
FT TANK."
FT /evidence="ECO:0000269|PubMed:14517219"
FT CONFLICT 134
FT /note="Missing (in Ref. 4; AAA56753)"
FT /evidence="ECO:0000305"
FT CONFLICT 158
FT /note="L -> F (in Ref. 6; BAH13910)"
FT /evidence="ECO:0000305"
FT CONFLICT 218..242
FT /note="Missing (in Ref. 3; AAA68195)"
FT /evidence="ECO:0000305"
FT CONFLICT 339
FT /note="P -> S (in Ref. 3; AAA68195)"
FT /evidence="ECO:0000305"
FT CONFLICT 405
FT /note="R -> G (in Ref. 4; AAA56753)"
FT /evidence="ECO:0000305"
FT TURN 54..56
FT /evidence="ECO:0007829|PDB:2ECY"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:2ECY"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:2ECY"
FT HELIX 74..81
FT /evidence="ECO:0007829|PDB:2ECY"
FT TURN 89..91
FT /evidence="ECO:0007829|PDB:2ECY"
FT TURN 97..99
FT /evidence="ECO:0007829|PDB:2ECY"
FT TURN 365..373
FT /evidence="ECO:0007829|PDB:1FLK"
FT TURN 375..377
FT /evidence="ECO:0007829|PDB:1FLL"
FT HELIX 378..410
FT /evidence="ECO:0007829|PDB:2GKW"
FT STRAND 415..423
FT /evidence="ECO:0007829|PDB:2GKW"
FT HELIX 425..433
FT /evidence="ECO:0007829|PDB:2GKW"
FT STRAND 438..441
FT /evidence="ECO:0007829|PDB:1L0A"
FT STRAND 445..448
FT /evidence="ECO:0007829|PDB:2GKW"
FT STRAND 453..459
FT /evidence="ECO:0007829|PDB:2GKW"
FT HELIX 464..466
FT /evidence="ECO:0007829|PDB:2GKW"
FT TURN 467..469
FT /evidence="ECO:0007829|PDB:2GKW"
FT STRAND 470..478
FT /evidence="ECO:0007829|PDB:2GKW"
FT HELIX 483..485
FT /evidence="ECO:0007829|PDB:2GKW"
FT STRAND 494..498
FT /evidence="ECO:0007829|PDB:2GKW"
FT STRAND 502..504
FT /evidence="ECO:0007829|PDB:1FLK"
FT STRAND 508..512
FT /evidence="ECO:0007829|PDB:2GKW"
FT STRAND 521..523
FT /evidence="ECO:0007829|PDB:1FLK"
FT STRAND 525..528
FT /evidence="ECO:0007829|PDB:2GKW"
FT STRAND 532..539
FT /evidence="ECO:0007829|PDB:2GKW"
FT HELIX 540..545
FT /evidence="ECO:0007829|PDB:2GKW"
FT STRAND 553..560
FT /evidence="ECO:0007829|PDB:2GKW"
FT STRAND 563..565
FT /evidence="ECO:0007829|PDB:1ZMS"
SQ SEQUENCE 568 AA; 64490 MW; 9456E440C0A90FBF CRC64;
MESSKKMDSP GALQTNPPLK LHTDRSAGTP VFVPEQGGYK EKFVKTVEDK YKCEKCHLVL
CSPKQTECGH RFCESCMAAL LSSSSPKCTA CQESIVKDKV FKDNCCKREI LALQIYCRNE
SRGCAEQLML GHLLVHLKND CHFEELPCVR PDCKEKVLRK DLRDHVEKAC KYREATCSHC
KSQVPMIALQ KHEDTDCPCV VVSCPHKCSV QTLLRSELSA HLSECVNAPS TCSFKRYGCV
FQGTNQQIKA HEASSAVQHV NLLKEWSNSL EKKVSLLQNE SVEKNKSIQS LHNQICSFEI
EIERQKEMLR NNESKILHLQ RVIDSQAEKL KELDKEIRPF RQNWEEADSM KSSVESLQNR
VTELESVDKS AGQVARNTGL LESQLSRHDQ MLSVHDIRLA DMDLRFQVLE TASYNGVLIW
KIRDYKRRKQ EAVMGKTLSL YSQPFYTGYF GYKMCARVYL NGDGMGKGTH LSLFFVIMRG
EYDALLPWPF KQKVTLMLMD QGSSRRHLGD AFKPDPNSSS FKKPTGEMNI ASGCPVFVAQ
TVLENGTYIK DDTIFIKVIV DTSDLPDP
