ID TRAF3_MOUSE Reviewed; 567 AA. AC Q60803; B2RPW3; Q62380; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 27-MAR-2024, entry version 205. DE RecName: Full=TNF receptor-associated factor 3 {ECO:0000312|MGI:MGI:108041}; DE EC=2.3.2.27; DE AltName: Full=CD40 receptor-associated factor 1 {ECO:0000303|PubMed:7533327}; DE Short=CRAF1 {ECO:0000312|MGI:MGI:108041}; DE AltName: Full=CD40-binding protein {ECO:0000312|MGI:MGI:108041}; DE Short=CD40BP {ECO:0000312|MGI:MGI:108041}; DE AltName: Full=RING-type E3 ubiquitin transferase TRAF3 {ECO:0000305}; GN Name=Traf3 {ECO:0000312|MGI:MGI:108041}; GN Synonyms=Cap-1 {ECO:0000312|MGI:MGI:108041}, Craf1 GN {ECO:0000303|PubMed:7533327}, Trafamn {ECO:0000303|PubMed:8660894}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH TNFRSF5. 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 [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC STRAIN=C57BL/6J; TISSUE=Brain; RX PubMed=8660894; DOI=10.1006/dbio.1996.0162; RA Wang X., Bornslaeger E.A., Haub O., Tomihara-Newberger C., Lonberg N., RA Dinulos M.B., Disteche C.M., Copeland N.G., Gilbert D.J., Jenkins N.A., RA Lacy E.; RT "A candidate gene for the amnionless gastrulation stage mouse mutation RT encodes a TRAF-related protein."; RL Dev. Biol. 177:274-290(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [5] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=8934568; DOI=10.1016/s1074-7613(00)80497-5; RA Xu Y., Cheng G., Baltimore D.; RT "Targeted disruption of TRAF3 leads to postnatal lethality and defective T- RT dependent immune responses."; RL Immunity 5:407-415(1996). RN [6] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=17015635; DOI=10.1084/jem.20061166; RA He J.Q., Zarnegar B., Oganesyan G., Saha S.K., Yamazaki S., Doyle S.E., RA Dempsey P.W., Cheng G.; RT "Rescue of TRAF3-null mice by p100 NF-kappa B deficiency."; RL J. Exp. Med. 203:2413-2418(2006). RN [7] RP FUNCTION, INTERACTION WITH MYD88, AND IDENTIFICATION IN A COMPLEX WITH RP TRAF6. RX PubMed=16306937; DOI=10.1038/nature04369; RA Hacker H., Redecke V., Blagoev B., Kratchmarova I., Hsu L.C., Wang G.G., RA Kamps M.P., Raz E., Wagner H., Hacker G., Mann M., Karin M.; RT "Specificity in Toll-like receptor signalling through distinct effector RT functions of TRAF3 and TRAF6."; RL Nature 439:204-207(2006). RN [8] RP INTERACTION WITH TICAM1, AND FUNCTION. RX PubMed=16306936; DOI=10.1038/nature04374; RA Oganesyan G., Saha S.K., Guo B., He J.Q., Shahangian A., Zarnegar B., RA Perry A., Cheng G.; RT "Critical role of TRAF3 in the Toll-like receptor-dependent and RT -independent antiviral response."; RL Nature 439:208-211(2006). RN [9] RP FUNCTION, DOMAIN, INTERACTION WITH MAP3K14, AND MUTAGENESIS OF CYS-52; RP CYS-55; CYS-67 AND HIS-69. RX PubMed=17158868; DOI=10.1074/jbc.m610271200; RA He J.Q., Saha S.K., Kang J.R., Zarnegar B., Cheng G.; RT "Specificity of TRAF3 in its negative regulation of the noncanonical NF- RT kappa B pathway."; RL J. Biol. Chem. 282:3688-3694(2007). RN [10] RP FUNCTION. RX PubMed=17723217; DOI=10.1016/j.immuni.2007.07.012; RA Xie P., Stunz L.L., Larison K.D., Yang B., Bishop G.A.; RT "Tumor necrosis factor receptor-associated factor 3 is a critical regulator RT of B cell homeostasis in secondary lymphoid organs."; RL Immunity 27:253-267(2007). RN [11] RP FUNCTION. RX PubMed=18313334; DOI=10.1016/j.immuni.2008.01.009; RA Gardam S., Sierro F., Basten A., Mackay F., Brink R.; RT "TRAF2 and TRAF3 signal adapters act cooperatively to control the RT maturation and survival signals delivered to B cells by the BAFF RT receptor."; RL Immunity 28:391-401(2008). RN [12] RP INTERACTION WITH TRAFD1. RX PubMed=18849341; DOI=10.1074/jbc.m806923200; RA Sanada T., Takaesu G., Mashima R., Yoshida R., Kobayashi T., Yoshimura A.; RT "FLN29 deficiency reveals its negative regulatory role in the Toll-like RT receptor (TLR) and retinoic acid-inducible gene I (RIG-I)-like helicase RT signaling pathway."; RL J. Biol. Chem. 283:33858-33864(2008). RN [13] RP FUNCTION, DISRUPTION PHENOTYPE, IDENTIFICATION IN A COMPLEX WITH TRAF2; RP BIRC3 AND MAP3K14, UBIQUITINATION, AND TISSUE SPECIFICITY. RX PubMed=18997792; DOI=10.1038/ni.1678; RA Vallabhapurapu S., Matsuzawa A., Zhang W., Tseng P.H., Keats J.J., Wang H., RA Vignali D.A., Bergsagel P.L., Karin M.; RT "Nonredundant and complementary functions of TRAF2 and TRAF3 in a RT ubiquitination cascade that activates NIK-dependent alternative NF-kappaB RT signaling."; RL Nat. Immunol. 9:1364-1370(2008). RN [14] RP FUNCTION, AND INTERACTION WITH MAP3K14. RX PubMed=18997794; DOI=10.1038/ni.1676; RA Zarnegar B.J., Wang Y., Mahoney D.J., Dempsey P.W., Cheung H.H., He J., RA Shiba T., Yang X., Yeh W.C., Mak T.W., Korneluk R.G., Cheng G.; RT "Noncanonical NF-kappaB activation requires coordinated assembly of a RT regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the RT kinase NIK."; RL Nat. Immunol. 9:1371-1378(2008). RN [15] RP FUNCTION. RX PubMed=19228877; DOI=10.1093/intimm/dxp013; RA Jabara H.H., Weng Y., Sannikova T., Geha R.S.; RT "TRAF2 and TRAF3 independently mediate Ig class switching driven by CD40."; RL Int. Immunol. 21:477-488(2009). RN [16] RP FUNCTION, E3 PROTEIN-UBIQUITIN LIGASE ACTIVITY, SUBUNIT, IDENTIFICATION IN RP A COMPLEX WITH TLR4; TRAF6; MAP3K7; MYD88; IKBKG; TICAM1; BIRC2; BIRC3 AND RP UBE2N, INTERACTION WITH TLR4, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RP UBIQUITINATION, AND MUTAGENESIS OF CYS-67; HIS-69; LYS-106 AND LYS-155. RX PubMed=19898473; DOI=10.1038/ni.1819; RA Tseng P.H., Matsuzawa A., Zhang W., Mino T., Vignali D.A., Karin M.; RT "Different modes of ubiquitination of the adaptor TRAF3 selectively RT activate the expression of type I interferons and proinflammatory RT cytokines."; RL Nat. Immunol. 11:70-75(2010). RN [17] 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 [18] RP UBIQUITINATION, AND DEUBIQUITINATION BY OTUD7B. RX PubMed=23334419; DOI=10.1038/nature11831; RA Hu H., Brittain G.C., Chang J.H., Puebla-Osorio N., Jin J., Zal A., RA Xiao Y., Cheng X., Chang M., Fu Y.X., Zal T., Zhu C., Sun S.C.; RT "OTUD7B controls non-canonical NF-kappaB activation through RT deubiquitination of TRAF3."; RL Nature 494:371-374(2013). RN [19] RP UBIQUITINATION AT LYS-328, AND MUTAGENESIS OF LYS-328 AND TRP-419. RX PubMed=23542741; DOI=10.1038/ni.2565; RA Chen B.B., Coon T.A., Glasser J.R., McVerry B.J., Zhao J., Zhao Y., Zou C., RA Ellis B., Sciurba F.C., Zhang Y., Mallampalli R.K.; RT "A combinatorial F box protein directed pathway controls TRAF adaptor RT stability to regulate inflammation."; RL Nat. Immunol. 14:470-479(2013). RN [20] RP FUNCTION, AND DEUBIQUITINATION BY MYSM1. RX PubMed=26474655; DOI=10.1016/j.immuni.2015.09.010; RA Panda S., Nilsson J.A., Gekara N.O.; RT "Deubiquitinase MYSM1 Regulates Innate Immunity through Inactivation of RT TRAF3 and TRAF6 Complexes."; RL Immunity 43:647-659(2015). RN [21] RP INTERACTION WITH PPP3CA AND PPP3CB. RX PubMed=26029823; DOI=10.1038/srep10758; RA Shinzawa M., Konno H., Qin J., Akiyama N., Miyauchi M., Ohashi H., RA Miyamoto-Sato E., Yanagawa H., Akiyama T., Inoue J.; RT "Catalytic subunits of the phosphatase calcineurin interact with NF-kappaB- RT inducing kinase (NIK) and attenuate NIK-dependent gene expression."; RL Sci. Rep. 5:10758-10758(2015). RN [22] RP FUNCTION, AND DEUBIQUITINATION BY USP25. RX PubMed=26305951; DOI=10.1073/pnas.1509968112; RA Lin D., Zhang M., Zhang M.X., Ren Y., Jin J., Zhao Q., Pan Z., Wu M., RA Shu H.B., Dong C., Zhong B.; RT "Induction of USP25 by viral infection promotes innate antiviral responses RT by mediating the stabilization of TRAF3 and TRAF6."; RL Proc. Natl. Acad. Sci. U.S.A. 112:11324-11329(2015). RN [23] RP FUNCTION, AND DEUBIQUITINATION BY USP25. RX PubMed=30579117; DOI=10.1016/j.molimm.2018.12.017; RA Wen J., Bai H., Chen N., Zhang W., Zhu X., Li P., Gong J.; RT "USP25 promotes endotoxin tolerance via suppressing K48-linked RT ubiquitination and degradation of TRAF3 in Kupffer cells."; RL Mol. Immunol. 106:53-62(2019). RN [24] {ECO:0007744|PDB:4GHU} RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 376-567, FUNCTION, INTERACTION RP WITH MAVS, AND MUTAGENESIS OF TYR-440 AND PHE-473. RX PubMed=23150880; DOI=10.1126/scisignal.2003152; RA Zhang P., Reichardt A., Liang H., Aliyari R., Cheng D., Wang Y., Xu F., RA Cheng G., Liu Y.; RT "Single amino acid substitutions confer the antiviral activity of the TRAF3 RT adaptor protein onto TRAF5."; RL Sci. Signal. 5:81-81(2012). 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:17015635). In TLR and RLR signaling pathways, acts CC as an E3 ubiquitin ligase promoting the synthesis of 'Lys-63'-linked CC polyubiquitin chains on several substrates such as ASC that lead to the CC activation of the type I interferon response or the inflammasome CC (PubMed:19898473, PubMed:23871208, PubMed:26305951, PubMed:23150880). CC Following the activation of certain TLRs such as TLR4, acts as a CC negative NF-kappa-B regulator, possibly to avoid unregulated CC inflammatory response, and its degradation via 'Lys-48'-linked CC polyubiquitination is required for MAPK activation and production of CC inflammatory cytokines (PubMed:16306937). Alternatively, when TLR4 CC orchestrates bacterial expulsion, TRAF3 undergoes 'Lys-33'-linked CC polyubiquitination and subsequently binds to RALGDS, mobilizing the CC exocyst complex to rapidly expel intracellular bacteria back for CC clearance. Acts also as a constitutive negative regulator of the CC alternative NF-kappa-B pathway, which controls B-cell survival and CC lymphoid organ development (PubMed:17723217). Required for normal CC antibody isotype switching from IgM to IgG (PubMed:19228877). Plays a CC role T-cell dependent immune responses (PubMed:8934568). Down-regulates CC proteolytic processing of NFKB2, and thereby inhibits non-canonical CC activation of NF-kappa-B. Promotes ubiquitination and proteasomal CC degradation of MAP3K14. {ECO:0000269|PubMed:16306936, CC ECO:0000269|PubMed:16306937, ECO:0000269|PubMed:17015635, CC ECO:0000269|PubMed:17158868, ECO:0000269|PubMed:17723217, CC ECO:0000269|PubMed:18313334, ECO:0000269|PubMed:18997792, CC ECO:0000269|PubMed:18997794, ECO:0000269|PubMed:19228877, CC ECO:0000269|PubMed:19898473, ECO:0000269|PubMed:26305951, CC ECO:0000269|PubMed:26474655, ECO:0000269|PubMed:30579117, CC ECO:0000269|PubMed:8934568}. 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 -!- 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 (By CC similarity). Identified in a complex with TRAF2, MAP3K14 and BIRC3. CC Upon exposure to bacterial lipopolysaccharide (LPS), recruited to a CC transient complex containing TLR4, TRAF3, TRAF6, IKBKG, MAP3K7, MYD88, CC TICAM1, BIRC2, BIRC3 and UBE2N. Interacts (via RING-type zinc finger CC domain) with SRC. Interacts with CARD14 (By similarity). Interacts (via CC MATH domain) with PTPN22; the interaction promotes TRAF3 CC polyubiquitination (PubMed:23871208). Interacts with MAVS CC (PubMed:23150880). Directly interacts with DDX3X; this interaction CC stimulates TRAF3 'Lys-63' ubiquitination (By similarity). Interacts CC with IRF3 (By similarity). Interacts with IKBKE in the course of viral CC infection (By similarity). Interacts with TRIM35 (By similarity). CC Interacts with GAPDH; promoting TRAF3 ubiquitination (By similarity). CC Interacts with PPP3CA and PPP3CB (PubMed:26029823). Interacts with CC RALGDS (By similarity). Interacts with FBXO11 (By similarity). CC {ECO:0000250|UniProtKB:Q13114, ECO:0000269|PubMed:23150880, CC ECO:0000269|PubMed:23871208, ECO:0000269|PubMed:26029823}. CC -!- INTERACTION: CC Q60803; Q8VCF0: Mavs; NbExp=4; IntAct=EBI-520135, EBI-3862816; CC Q60803; P22366: Myd88; NbExp=5; IntAct=EBI-520135, EBI-525108; CC Q60803; Q80UF7: Ticam1; NbExp=2; IntAct=EBI-520135, EBI-3649271; CC Q60803; O35305: Tnfrsf11a; NbExp=3; IntAct=EBI-520135, EBI-647362; CC Q60803; P39429: Traf2; NbExp=2; IntAct=EBI-520135, EBI-520016; CC Q60803; P62991: Ubc; NbExp=2; IntAct=EBI-520135, EBI-413074; CC Q60803; Q9Y2R2: PTPN22; Xeno; NbExp=5; IntAct=EBI-520135, EBI-1211241; CC Q60803; Q9UHD2: TBK1; Xeno; NbExp=2; IntAct=EBI-520135, EBI-356402; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19898473}. Endosome CC {ECO:0000269|PubMed:19898473}. Mitochondrion CC {ECO:0000250|UniProtKB:Q13114}. Note=Undergoes endocytosis together CC with TLR4 upon LPS signaling (PubMed:19898473). Co-localized to CC mitochondria with TRIM35 (By similarity). CC {ECO:0000250|UniProtKB:Q13114, ECO:0000269|PubMed:19898473}. CC -!- TISSUE SPECIFICITY: Detected in bone marrow macrophages and spleen B- CC cells (at protein level). In adult, highest in brain. Also found in CC kidney, heart, thymus, spleen, lung, muscle, testis and ovary. Not CC found in liver. {ECO:0000269|PubMed:18997792, CC ECO:0000269|PubMed:19898473, ECO:0000269|PubMed:8660894}. CC -!- DEVELOPMENTAL STAGE: In the embryo, expressed from 6.5 dpc with highest CC levels found between 11.5 dpc and 13.5 dpc. At late stages of CC gestation, from 14.5 dpc, only low levels are detected. CC -!- DOMAIN: The MATH/TRAF domain binds to receptor cytoplasmic domains. CC {ECO:0000269|PubMed:17158868}. CC -!- DOMAIN: The Ring-type zinc finger domain is required for its function CC in down-regulation of NFKB2 proteolytic processing. CC {ECO:0000269|PubMed:17158868}. CC -!- PTM: Undergoes 'Lys-48'-linked polyubiquitination, leading to its CC proteasomal degradation in response to signaling by TNFSF13B, TLR4 or CC through CD40 (PubMed:19898473). 'Lys-48'-linked polyubiquitinated form CC is deubiquitinated by OTUD7B, preventing TRAF3 proteolysis and over- CC activation of non-canonical NF-kappa-B (PubMed:23334419). Undergoes CC 'Lys-63'-linked ubiquitination during early stages of virus infection, CC and 'Lys-48'-linked ubiquitination during later stages. Undergoes both CC 'Lys-48'-linked and 'Lys-63'-linked ubiquitination in response to TLR3 CC and TLR4 signaling. 'Lys-63'-linked ubiquitination can be mediated by CC TRIM35. Deubiquitinated by OTUB1, OTUB2 and OTUD5. Undergoes 'Lys-63'- CC linked deubiquitination by MYSM1 to terminate the pattern-recognition CC receptors/PRRs pathways (PubMed:26474655). Ubiquitinated at Lys-328 by CC the SCF(FBXL2) complex, leading to its degradation by the proteasome CC (PubMed:23542741). {ECO:0000269|PubMed:18997792, CC ECO:0000269|PubMed:19898473, ECO:0000269|PubMed:23334419, CC ECO:0000269|PubMed:23542741, ECO:0000269|PubMed:26474655}. 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-55 CC and Cys-123 by NEDD4L; leading to increased 'Lys-48'- and 'Lys-63'- CC linked ubiquitination as well as increased binding to TBK1. TLR4 CC signals emanating from bacteria containing vesicles trigger 'Lys-33'- CC linked polyubiquitination that promotes the assembly of the exocyst CC complex thereby connecting innate immune signaling to the cellular CC trafficking apparatus (By similarity). Deubiquitinated by USP25 during CC viral infection, leading to TRAF3 stabilization and type I interferon CC production (PubMed:26305951). 'Lys-63'-linked ubiquitination by FBXO11 CC in a NEDD8-dependent manner promotes the amplification of IFN-I CC signaling (By similarity). {ECO:0000250|UniProtKB:Q13114, CC ECO:0000269|PubMed:18997792, ECO:0000269|PubMed:19898473, CC ECO:0000269|PubMed:23334419, ECO:0000269|PubMed:26305951, CC ECO:0000269|PubMed:26474655, ECO:0000269|PubMed:30579117}. CC -!- DISRUPTION PHENOTYPE: Newborns appear normal, but do not thrive. Their CC blood glucose levels and leukocyte levels decrease steadily, the spleen CC size is dramatically reduced, and they become progressively runted. CC They die about ten days after birth. Mice exhibit abnormally high CC MAP3K14 protein levels and constitutive proteolytic processing of CC NFKB2/p100, leading to constitutive activation of NF-kappa-B. CC {ECO:0000269|PubMed:17015635, ECO:0000269|PubMed:18997792, CC ECO:0000269|PubMed:8934568}. CC -!- SIMILARITY: Belongs to the TNF receptor-associated factor family. A CC subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U21050; AAC52175.1; -; mRNA. DR EMBL; U33840; AAC52710.1; -; mRNA. DR EMBL; CH466549; EDL18642.1; -; Genomic_DNA. DR EMBL; BC137634; AAI37635.1; -; mRNA. DR EMBL; BC137635; AAI37636.1; -; mRNA. DR CCDS; CCDS26175.1; -. DR PIR; I49272; I49272. DR RefSeq; NP_035762.2; NM_011632.3. DR RefSeq; XP_006515861.1; XM_006515798.2. DR RefSeq; XP_006515862.1; XM_006515799.1. DR RefSeq; XP_006515863.1; XM_006515800.2. DR RefSeq; XP_006515864.1; XM_006515801.2. DR PDB; 4GHU; X-ray; 2.20 A; A=376-567. DR PDBsum; 4GHU; -. DR AlphaFoldDB; Q60803; -. DR SMR; Q60803; -. DR BioGRID; 204304; 96. DR DIP; DIP-34050N; -. DR IntAct; Q60803; 34. DR MINT; Q60803; -. DR STRING; 10090.ENSMUSP00000021706; -. DR iPTMnet; Q60803; -. DR PhosphoSitePlus; Q60803; -. DR SwissPalm; Q60803; -. DR EPD; Q60803; -. DR MaxQB; Q60803; -. DR PaxDb; 10090-ENSMUSP00000021706; -. DR PeptideAtlas; Q60803; -. DR ProteomicsDB; 258961; -. DR Pumba; Q60803; -. DR Antibodypedia; 129; 599 antibodies from 44 providers. DR DNASU; 22031; -. DR Ensembl; ENSMUST00000021706.11; ENSMUSP00000021706.5; ENSMUSG00000021277.17. DR GeneID; 22031; -. DR KEGG; mmu:22031; -. DR UCSC; uc007pcl.2; mouse. DR AGR; MGI:108041; -. DR CTD; 7187; -. DR MGI; MGI:108041; Traf3. DR VEuPathDB; HostDB:ENSMUSG00000021277; -. DR eggNOG; KOG0297; Eukaryota. DR GeneTree; ENSGT00940000160538; -. DR InParanoid; Q60803; -. DR OMA; ETVCPSF; -. DR OrthoDB; 2913784at2759; -. DR PhylomeDB; Q60803; -. DR TreeFam; TF321154; -. DR Reactome; R-MMU-5668541; TNFR2 non-canonical NF-kB pathway. DR Reactome; R-MMU-5676594; TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway. DR Reactome; R-MMU-5689896; Ovarian tumor domain proteases. DR Reactome; R-MMU-936964; Activation of IRF3, IRF7 mediated by TBK1, IKBKE. DR BioGRID-ORCS; 22031; 22 hits in 86 CRISPR screens. DR ChiTaRS; Traf3; mouse. DR PRO; PR:Q60803; -. DR Proteomes; UP000000589; Chromosome 12. DR RNAct; Q60803; Protein. DR Bgee; ENSMUSG00000021277; Expressed in CA3 field of hippocampus and 255 other cell types or tissues. DR ExpressionAtlas; Q60803; baseline and differential. DR GO; GO:0035631; C:CD40 receptor complex; IDA:BHF-UCL. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:BHF-UCL. DR GO; GO:0005768; C:endosome; ISO:MGI. DR GO; GO:0010008; C:endosome membrane; IEA:Ensembl. DR GO; GO:0005739; C:mitochondrion; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI. DR GO; GO:0031996; F:thioesterase binding; ISO:MGI. DR GO; GO:0005164; F:tumor necrosis factor receptor binding; ISO:MGI. DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISO:MGI. DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:MGI. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0045087; P:innate immune response; IEA:InterPro. DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:UniProtKB. DR GO; GO:0032481; P:positive regulation of type I interferon production; ISO:MGI. 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:0043122; P:regulation of canonical NF-kappaB signal transduction; IBA:GO_Central. DR GO; GO:0001817; P:regulation of cytokine production; IMP:UniProtKB. DR GO; GO:0050688; P:regulation of defense response to virus; IMP:UniProtKB. DR GO; GO:0032648; P:regulation of interferon-beta production; IMP:UniProtKB. DR GO; GO:0030162; P:regulation of proteolysis; IDA:UniProtKB. DR GO; GO:0008063; P:Toll signaling pathway; IEA:InterPro. DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IEA:Ensembl. DR GO; GO:0002224; P:toll-like receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB. DR CDD; cd03777; MATH_TRAF3; 1. DR CDD; cd16640; RING-HC_TRAF3; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 3. DR InterPro; IPR002083; MATH/TRAF_dom. DR InterPro; IPR012227; TNF_rcpt-assoc_TRAF_met. DR InterPro; IPR008974; TRAF-like. DR InterPro; IPR049440; TRAF3/5_RING. DR InterPro; IPR037304; TRAF3_MATH. DR InterPro; IPR027128; TRAF3_RING-HC. DR InterPro; IPR049342; TRAF_MEP1_MATH_dom. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR InterPro; IPR001293; Znf_TRAF. DR PANTHER; PTHR10131; TNF RECEPTOR ASSOCIATED FACTOR; 1. DR PANTHER; PTHR10131:SF76; TNF RECEPTOR-ASSOCIATED FACTOR 3; 1. DR Pfam; PF21355; TRAF-mep_MATH; 1. DR Pfam; PF21363; TRAF3_RING; 1. DR Pfam; PF02176; zf-TRAF; 1. DR PIRSF; PIRSF015614; TRAF; 1. DR SMART; SM00061; MATH; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR SUPFAM; SSF49599; TRAF domain-like; 3. DR SUPFAM; SSF57953; Trimerization domain of TRAF; 1. DR PROSITE; PS50144; MATH; 1. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. DR PROSITE; PS50145; ZF_TRAF; 2. DR Genevisible; Q60803; MM. PE 1: Evidence at protein level; KW 3D-structure; Apoptosis; Coiled coil; Cytoplasm; Endosome; Immunity; KW Isopeptide bond; Metal-binding; Mitochondrion; Reference proteome; Repeat; KW Thioester bond; Transferase; Ubl conjugation; Ubl conjugation pathway; KW Zinc; Zinc-finger. FT CHAIN 1..567 FT /note="TNF receptor-associated factor 3" FT /id="PRO_0000056402" FT DOMAIN 414..559 FT /note="MATH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00129" FT ZN_FING 67..76 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT ZN_FING 134..189 FT /note="TRAF-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00207" FT ZN_FING 190..248 FT /note="TRAF-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00207" FT REGION 1..26 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 266..337 FT /evidence="ECO:0000255" FT CROSSLNK 55 FT /note="Glycyl cysteine thioester (Cys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q13114" FT CROSSLNK 106 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000305" FT CROSSLNK 123 FT /note="Glycyl cysteine thioester (Cys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q13114" FT CROSSLNK 155 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000305" FT CROSSLNK 167 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q13114" FT CROSSLNK 328 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:23542741" FT MUTAGEN 52 FT /note="C->A: Abolishes inhibition of NFKB2 processing; when FT associated with A-55." FT /evidence="ECO:0000269|PubMed:17158868" FT MUTAGEN 55 FT /note="C->A: Abolishes inhibition of NFKB2 processing; when FT associated with A-52." FT /evidence="ECO:0000269|PubMed:17158868" FT MUTAGEN 67 FT /note="C->A: Strongly reduces 'Lys-63'-linked FT ubiquitination; when associated with A-69. Abolishes FT inhibition of NFKB2 processing; when associated with A-69." FT /evidence="ECO:0000269|PubMed:17158868, FT ECO:0000269|PubMed:19898473" FT MUTAGEN 69 FT /note="H->A: Strongly reduces 'Lys-63'-linked FT ubiquitination; when associated with A-69. Abolishes FT inhibition of NFKB2 processing; when associated with A-67." FT /evidence="ECO:0000269|PubMed:17158868, FT ECO:0000269|PubMed:19898473" FT MUTAGEN 106 FT /note="K->R: Reduces 'Lys-48'-linked polyubiquitination; FT when associated with R-155." FT /evidence="ECO:0000269|PubMed:19898473" FT MUTAGEN 155 FT /note="K->R: Reduces 'Lys-48'-linked polyubiquitination; FT when associated with R-106." FT /evidence="ECO:0000269|PubMed:19898473" FT MUTAGEN 328 FT /note="K->R: Abolished ubiquitination by the SCF(FBXL2) FT complex." FT /evidence="ECO:0000269|PubMed:23542741" FT MUTAGEN 419 FT /note="W->A: Decreased interaction with FBXL2." FT /evidence="ECO:0000269|PubMed:23542741" FT MUTAGEN 440 FT /note="Y->F: Loss of interaction with MAVS." FT /evidence="ECO:0000269|PubMed:23150880" FT MUTAGEN 473 FT /note="F->Y: Loss of interaction with MAVS." FT /evidence="ECO:0000269|PubMed:23150880" FT CONFLICT 72..73 FT /note="CE -> WQ (in Ref. 2; AAC52710)" FT /evidence="ECO:0000305" FT CONFLICT 390 FT /note="M -> T (in Ref. 1; AAC52175)" FT /evidence="ECO:0000305" FT HELIX 377..409 FT /evidence="ECO:0007829|PDB:4GHU" FT STRAND 413..421 FT /evidence="ECO:0007829|PDB:4GHU" FT HELIX 424..432 FT /evidence="ECO:0007829|PDB:4GHU" FT STRAND 444..447 FT /evidence="ECO:0007829|PDB:4GHU" FT STRAND 452..458 FT /evidence="ECO:0007829|PDB:4GHU" FT HELIX 463..465 FT /evidence="ECO:0007829|PDB:4GHU" FT TURN 466..468 FT /evidence="ECO:0007829|PDB:4GHU" FT STRAND 469..477 FT /evidence="ECO:0007829|PDB:4GHU" FT HELIX 482..484 FT /evidence="ECO:0007829|PDB:4GHU" FT STRAND 493..497 FT /evidence="ECO:0007829|PDB:4GHU" FT STRAND 507..511 FT /evidence="ECO:0007829|PDB:4GHU" FT HELIX 518..520 FT /evidence="ECO:0007829|PDB:4GHU" FT STRAND 524..527 FT /evidence="ECO:0007829|PDB:4GHU" FT STRAND 531..538 FT /evidence="ECO:0007829|PDB:4GHU" FT HELIX 539..544 FT /evidence="ECO:0007829|PDB:4GHU" FT STRAND 552..559 FT /evidence="ECO:0007829|PDB:4GHU" SQ SEQUENCE 567 AA; 64294 MW; EC282EFFF84E5A3F CRC64; MESSKKMDAA GTLQPNPPLK LQPDRGAGSV LVPEQGGYKE KFVKTVEDKY KCEKCRLVLC NPKQTECGHR FCESCMAALL SSSSPKCTAC QESIIKDKVF KDNCCKREIL ALQVYCRNEG RGCAEQLTLG HLLVHLKNEC QFEELPCLRA DCKEKVLRKD LRDHVEKACK YREATCSHCK SQVPMIKLQK HEDTDCPCVV VSCPHKCSVQ TLLRSELSAH LSECVNAPST CSFKRYGCVF QGTNQQIKAH EASSAVQHVN LLKEWSNSLE KKVSLLQNES VEKNKSIQSL HNQICSFEIE IERQKEMLRN NESKILHLQR VIDSQAEKLK ELDKEIRPFR QNWEEADSMK SSVESLQNRV TELESVDKSA GQAARNTGLL ESQLSRHDQM LSVHDIRLAD MDLRFQVLET ASYNGVLIWK IRDYKRRKQE AVMGKTLSLY SQPFYTGYFG YKMCARVYLN GDGMGKGTHL SLFFVIMRGE YDALLPWPFK QKVTLMLMDQ GSSRRHLGDA FKPDPNSSSF KKPTGEMNIA SGCPVFVAQT VLENGTYIKD DTIFIKVIVD TSDLPDP //