T3JAM_MOUSE
ID T3JAM_MOUSE Reviewed; 513 AA.
AC Q8C0G2; Q8BY50; Q8K1Y9;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 2.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=TRAF3-interacting JNK-activating modulator;
DE AltName: Full=TRAF3-interacting protein 3;
GN Name=Traf3ip3; Synonyms=T3jam;
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], TISSUE SPECIFICITY, AND INTERACTION WITH TRAF3.
RC STRAIN=C57BL/6J;
RX PubMed=14572659; DOI=10.1016/s0014-5793(03)01072-x;
RA Dadgostar H., Doyle S.E., Shahangian A., Garcia D.E., Cheng G.;
RT "T3JAM, a novel protein that specifically interacts with TRAF3 and promotes
RT the activation of JNK.";
RL FEBS Lett. 553:403-407(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Testis, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=26195727; DOI=10.1084/jem.20150110;
RA Zou Q., Jin J., Xiao Y., Hu H., Zhou X., Jie Z., Xie X., Li J.Y., Cheng X.,
RA Sun S.C.;
RT "T cell development involves TRAF3IP3-mediated ERK signaling in the
RT Golgi.";
RL J. Exp. Med. 212:1323-1336(2015).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP PPP2CA.
RX PubMed=30115741; DOI=10.1084/jem.20180397;
RA Yu X., Teng X.L., Wang F., Zheng Y., Qu G., Zhou Y., Hu Z., Wu Z.,
RA Chang Y., Chen L., Li H.B., Su B., Lu L., Liu Z., Sun S.C., Zou Q.;
RT "Metabolic control of regulatory T cell stability and function by TRAF3IP3
RT at the lysosome.";
RL J. Exp. Med. 215:2463-2476(2018).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=31390091; DOI=10.15252/embj.2019102075;
RA Zhu W., Li J., Zhang R., Cai Y., Wang C., Qi S., Chen S., Liang X., Qi N.,
RA Hou F.;
RT "TRAF3IP3 mediates the recruitment of TRAF3 to MAVS for antiviral innate
RT immunity.";
RL EMBO J. 38:e102075-e102075(2019).
CC -!- FUNCTION: Adapter protein that plays essential roles in both innate and
CC adaptive immunity. Plays a crucial role in the regulation of thymocyte
CC development (PubMed:26195727). Mechanistically, mediates TCR-stimulated
CC activation through recruiting MAP2K1/MEK1 to the Golgi and, thereby,
CC facilitating the interaction of MAP2K1/MEK1 with its activator BRAF
CC (PubMed:26195727). Also plays an essential role in regulatory T-cell
CC stability and function by recruiting the serine-threonine phosphatase
CC catalytic subunit (PPP2CA) to the lysosome, thereby facilitating the
CC interaction of PP2Ac with the mTORC1 component RPTOR and restricting
CC glycolytic metabolism (PubMed:30115741). Positively regulates TLR4
CC signaling activity in macrophage-mediated inflammation by acting as a
CC molecular clamp to facilitate LPS-induced translocation of TLR4 to
CC lipid rafts (PubMed:30115741). In response to viral infection,
CC facilitates the recruitment of TRAF3 to MAVS within mitochondria
CC leading to IRF3 activation and interferon production (PubMed:30115741).
CC However, participates in the maintenance of immune homeostasis and the
CC prevention of overzealous innate immunity by promoting 'Lys-48'-
CC dependent ubiquitination of TBK1 (By similarity).
CC {ECO:0000250|UniProtKB:Q9Y228, ECO:0000269|PubMed:26195727,
CC ECO:0000269|PubMed:30115741}.
CC -!- SUBUNIT: Interacts (via its coiled-coil domain) with TRAF3 (via
CC isoleucine zipper). Interacts with MAP2K1 (By similarity). Interacts
CC with PPP2CA; this interaction targets PPP2CA to the lysosomes (By
CC similarity). Interacts with MAVS (By similarity). Interacts with TBK1
CC (By similarity). {ECO:0000250|UniProtKB:Q9Y228}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9Y228}.
CC Golgi apparatus membrane {ECO:0000269|PubMed:26195727}; Single-pass
CC type IV membrane protein {ECO:0000305}. Lysosome membrane
CC {ECO:0000269|PubMed:30115741}. Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q9Y228}. Note=Accumulates on the mitochondria
CC after virus infection. {ECO:0000250|UniProtKB:Q9Y228}.
CC -!- TISSUE SPECIFICITY: Expressed in bone marrow, spleen and thymus. Not
CC detected in heart, kidney and liver. {ECO:0000269|PubMed:14572659}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice have considerably lower frequencies
CC of CD4(+) and CD8(+) single positive thymocytes, and concomitantly
CC higher frequencies of double positive thymocytes (PubMed:26195727).
CC TRAF3IP3 deletion also affects regulatory T-cell transcriptional
CC programs and stability (PubMed:30115741). In addition, mice show a
CC severely compromised potential to induce interferon production and are
CC vulnerable to RNA virus infection (PubMed:31390091).
CC {ECO:0000269|PubMed:26195727, ECO:0000269|PubMed:30115741,
CC ECO:0000269|PubMed:31390091}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ84304.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAQ84304.1; Type=Miscellaneous discrepancy; Note=Sequencing errors.; Evidence={ECO:0000305};
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DR EMBL; AY383616; AAQ84304.1; ALT_SEQ; mRNA.
DR EMBL; AK031400; BAC27388.1; -; mRNA.
DR EMBL; AK041994; BAC31127.2; -; mRNA.
DR EMBL; BC036561; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS15634.1; -.
DR RefSeq; NP_694777.3; NM_153137.4.
DR AlphaFoldDB; Q8C0G2; -.
DR SMR; Q8C0G2; -.
DR BioGRID; 229607; 4.
DR STRING; 10090.ENSMUSP00000040977; -.
DR MEROPS; S01.372; -.
DR iPTMnet; Q8C0G2; -.
DR PhosphoSitePlus; Q8C0G2; -.
DR EPD; Q8C0G2; -.
DR MaxQB; Q8C0G2; -.
DR PaxDb; Q8C0G2; -.
DR PRIDE; Q8C0G2; -.
DR ProteomicsDB; 254640; -.
DR DNASU; 215243; -.
DR GeneID; 215243; -.
DR KEGG; mmu:215243; -.
DR CTD; 80342; -.
DR MGI; MGI:2441706; Traf3ip3.
DR eggNOG; ENOG502RG0V; Eukaryota.
DR InParanoid; Q8C0G2; -.
DR OrthoDB; 484467at2759; -.
DR PhylomeDB; Q8C0G2; -.
DR BioGRID-ORCS; 215243; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Traf3ip3; mouse.
DR PRO; PR:Q8C0G2; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8C0G2; protein.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
PE 1: Evidence at protein level;
KW Cell membrane; Coiled coil; Golgi apparatus; Lysosome; Membrane;
KW Mitochondrion; Mitochondrion outer membrane; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..513
FT /note="TRAF3-interacting JNK-activating modulator"
FT /id="PRO_0000072404"
FT TOPO_DOM 1..485
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 486..506
FT /note="Helical; Anchor for type IV membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 507..513
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 1..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 130..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 381..402
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 266..488
FT /evidence="ECO:0000255"
FT COMPBIAS 18..82
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 150..167
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 381..396
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 185
FT /note="N -> K (in Ref. 2; BAC27388/BAC31127)"
FT /evidence="ECO:0000305"
FT CONFLICT 355
FT /note="D -> G (in Ref. 2; BAC27388)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 513 AA; 58564 MW; 6FF754048DB64353 CRC64;
MISSDSRSSP GLARWAESYE AKCERRQETR ENRRRRRNET TCRQPGKVLR TQHKERLQGA
RQLQFLKRRN LEEEKKGQAR EQGPSSKTDG GTGQVSILKE SLPGANKASF PGQQETGISS
EVFPALHHSS SGIQRDLGGH HASHGRAFPP QDSDIKKPHR QHRGTQTKAE EALPTIKNDA
SQQTNCGVAV LDKDIIQLSE YLKEALHREL ILKKKMVILQ DLLPALIRAS DSSWKGQLNE
DKLKGKLRSL ENQLYTCLQK HSPWGMKKVL LEMEDQRSSY EQKAKASLQK VLEEKMCAEQ
QLQRAQLSLA LAEQKCQEWK SQYEALKEDW RTLGDQHREL ESQLHVLQSK LQGADSRDSQ
MSQALQLLEN EHQELQTKLE SLQGDGEQQS SETQDLQDQL KKSEEEKQAL VSKVQQLQSL
LQNQSLQLQE QEKLLKKDQG LPVWNPKLSL DEVKPEGTRK EKEEELRDQL QKETFQLQVK
ENELQCGQWL PVLMVVIATA LAVFLANKGN LVI
