TRAF3_MOUSE
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 03-AUG-2022, entry version 196.
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},
GN Craf1 {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 FUNCTION, AND DEUBUQUITINATION 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 [20]
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 [21]
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 [22]
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 [23] {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). {ECO:0000250|UniProtKB:Q13114,
CC ECO:0000269|PubMed:23150880, ECO:0000269|PubMed:23871208,
CC 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. '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.
CC {ECO:0000269|PubMed:18997792, ECO:0000269|PubMed:19898473,
CC ECO:0000269|PubMed:23334419, 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). {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}.
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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; 38.
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; Q60803; -.
DR PeptideAtlas; Q60803; -.
DR PRIDE; Q60803; -.
DR ProteomicsDB; 258961; -.
DR Antibodypedia; 129; 540 antibodies from 44 providers.
DR DNASU; 22031; -.
DR Ensembl; ENSMUST00000021706; ENSMUSP00000021706; ENSMUSG00000021277.
DR GeneID; 22031; -.
DR KEGG; mmu:22031; -.
DR UCSC; uc007pcl.2; mouse.
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; 918518at2759; -.
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/IKK epsilon.
DR BioGRID-ORCS; 22031; 22 hits in 81 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 252 other tissues.
DR ExpressionAtlas; Q60803; baseline and differential.
DR Genevisible; Q60803; MM.
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; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
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:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; 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: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; IMP:UniProtKB.
DR GO; GO:0050688; P:regulation of defense response to virus; IMP: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; 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: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 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; 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 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 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
