CIKS_MOUSE
ID CIKS_MOUSE Reviewed; 555 AA.
AC Q8N7N6; Q8BH33;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=E3 ubiquitin ligase TRAF3IP2;
DE EC=2.3.2.27 {ECO:0000269|PubMed:19825828};
DE AltName: Full=Adapter protein CIKS;
DE AltName: Full=Connection to IKK and SAPK/JNK;
DE AltName: Full=E3 ubiquitin-protein ligase CIKS;
DE AltName: Full=Nuclear factor NF-kappa-B activator 1;
DE Short=ACT1;
DE AltName: Full=TRAF3-interacting protein 2;
GN Name=Traf3ip2 {ECO:0000312|MGI:MGI:2143599};
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].
RC STRAIN=C57BL/6J; TISSUE=Heart, and Thymus;
RX PubMed=12466851; DOI=10.1038/nature01266;
RA Okazaki Y., Furuno M., Kasukawa T., Adachi J., Bono H., Kondo S.,
RA Nikaido I., Osato N., Saito R., Suzuki H., Yamanaka I., Kiyosawa H.,
RA Yagi K., Tomaru Y., Hasegawa Y., Nogami A., Schonbach C., Gojobori T.,
RA Baldarelli R., Hill D.P., Bult C., Hume D.A., Quackenbush J., Schriml L.M.,
RA Kanapin A., Matsuda H., Batalov S., Beisel K.W., Blake J.A., Bradt D.,
RA Brusic V., Chothia C., Corbani L.E., Cousins S., Dalla E., Dragani T.A.,
RA Fletcher C.F., Forrest A., Frazer K.S., Gaasterland T., Gariboldi M.,
RA Gissi C., Godzik A., Gough J., Grimmond S., Gustincich S., Hirokawa N.,
RA Jackson I.J., Jarvis E.D., Kanai A., Kawaji H., Kawasawa Y.,
RA Kedzierski R.M., King B.L., Konagaya A., Kurochkin I.V., Lee Y.,
RA Lenhard B., Lyons P.A., Maglott D.R., Maltais L., Marchionni L.,
RA McKenzie L., Miki H., Nagashima T., Numata K., Okido T., Pavan W.J.,
RA Pertea G., Pesole G., Petrovsky N., Pillai R., Pontius J.U., Qi D.,
RA Ramachandran S., Ravasi T., Reed J.C., Reed D.J., Reid J., Ring B.Z.,
RA Ringwald M., Sandelin A., Schneider C., Semple C.A., Setou M., Shimada K.,
RA Sultana R., Takenaka Y., Taylor M.S., Teasdale R.D., Tomita M., Verardo R.,
RA Wagner L., Wahlestedt C., Wang Y., Watanabe Y., Wells C., Wilming L.G.,
RA Wynshaw-Boris A., Yanagisawa M., Yang I., Yang L., Yuan Z., Zavolan M.,
RA Zhu Y., Zimmer A., Carninci P., Hayatsu N., Hirozane-Kishikawa T.,
RA Konno H., Nakamura M., Sakazume N., Sato K., Shiraki T., Waki K., Kawai J.,
RA Aizawa K., Arakawa T., Fukuda S., Hara A., Hashizume W., Imotani K.,
RA Ishii Y., Itoh M., Kagawa I., Miyazaki A., Sakai K., Sasaki D., Shibata K.,
RA Shinagawa A., Yasunishi A., Yoshino M., Waterston R., Lander E.S.,
RA Rogers J., Birney E., Hayashizaki Y.;
RT "Analysis of the mouse transcriptome based on functional annotation of
RT 60,770 full-length cDNAs.";
RL Nature 420:563-573(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Oshima A., Takahashi-Fujii A., Tanase T., Imose N., Takeuchi K., Arita M.,
RA Musashino K., Yuuki H., Hara H., Sugiyama T., Irie R., Otsuki T., Sato H.,
RA Ota T., Wakamatsu A., Ishii S., Yamamoto J., Isono Y., Kawai-Hio Y.,
RA Saito K., Nishikawa T., Kimura K., Yamashita H., Matsuo K., Nakamura Y.,
RA Sekine M., Kikuchi H., Kanda K., Wagatsuma M., Murakawa K., Kanehori K.,
RA Sugiyama A., Kawakami B., Suzuki Y., Sugano S., Nagahari K., Masuho Y.,
RA Nagai K., Isogai T.;
RT "NEDO cDNA sequencing project.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Yoshida T., Chandrasekar B.;
RT "Heart and Vascular Institute, Tulane University School of Medicine, 1430
RT Tulane Ave. SL-48, New Orleans, LA 70112, USA.";
RL Submitted (SEP-2012) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Worley K.C.;
RT "Human Genome Sequencing Center, Baylor College of Medicine, One Baylor
RT Plaza, Houston, TX 77030, USA.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12477932; DOI=10.1073/pnas.242603899;
RG Mammalian Gene Collection Program Team;
RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., Klausner R.D.,
RA Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., Altschul S.F.,
RA Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., Hopkins R.F., Jordan H.,
RA Moore T., Max S.I., Wang J., Hsieh F., Diatchenko L., Marusina K.,
RA Farmer A.A., Rubin G.M., Hong L., Stapleton M., Soares M.B., Bonaldo M.F.,
RA Casavant T.L., Scheetz T.E., Brownstein M.J., Usdin T.B., Toshiyuki S.,
RA Carninci P., Prange C., Raha S.S., Loquellano N.A., Peters G.J.,
RA Abramson R.D., Mullahy S.J., Bosak S.A., McEwan P.J., McKernan K.J.,
RA Malek J.A., Gunaratne P.H., Richards S., Worley K.C., Hale S., Garcia A.M.,
RA Gay L.J., Hulyk S.W., Villalon D.K., Muzny D.M., Sodergren E.J., Lu X.,
RA Gibbs R.A., Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S.,
RA Sanchez A., Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., Rodriguez A.C.,
RA Grimwood J., Schmutz J., Myers R.M., Butterfield Y.S., Krzywinski M.I.,
RA Skalska U., Smailus D.E., Schnerch A., Schein J.E., Jones S.J., Marra M.A.;
RT "Generation and initial analysis of more than 15,000 full-length human and
RT mouse cDNA sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF LEU-286.
RX PubMed=19825828; DOI=10.1126/scisignal.2000382;
RA Liu C., Qian W., Qian Y., Giltiay N.V., Lu Y., Swaidani S., Misra S.,
RA Deng L., Chen Z.J., Li X.;
RT "Act1, a U-box E3 ubiquitin ligase for IL-17 signaling.";
RL Sci. Signal. 2:ra63-ra63(2009).
RN [7]
RP INTERACTION WITH IL17RA AND TRAF6, AND FUNCTION.
RX PubMed=33723527; DOI=10.1016/j.isci.2021.102293;
RA Lin X., Fu B., Yin S., Li Z., Liu H., Zhang H., Xing N., Wang Y., Xue W.,
RA Xiong Y., Zhang S., Zhao Q., Xu S., Zhang J., Wang P., Nian W., Wang X.,
RA Wu H.;
RT "Title: ORF8 contributes to cytokine storm during SARS-CoV-2 infection by
RT activating IL-17 pathway.";
RL IScience 1:102293-102293(2021).
CC -!- FUNCTION: E3 ubiquitin ligase that catalyzes 'Lys63'-linked
CC polyubiquitination of target protein, enhancing protein-protein
CC interaction and cell signaling (By similarity). Transfers ubiquitin
CC from E2 ubiquitin-conjugating enzyme UBE2V1-UBE2N to substrate protein
CC (By similarity). Essential adapter molecule in IL17A-mediated signaling
CC (PubMed:19825828). Upon IL17A stimulation, interacts with IL17RA and
CC IL17RC receptor chains through SEFIR domains and catalyzes 'Lys63'-
CC linked polyubiquitination of TRAF6, leading to TRAF6-mediated
CC activation of NF-kappa-B and MAPkinase pathways (PubMed:19825828).
CC {ECO:0000250|UniProtKB:O43734, ECO:0000269|PubMed:19825828,
CC ECO:0000269|PubMed:33723527}.
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:19825828};
CC -!- SUBUNIT: Interacts with IKBKG/NF-kappa B essential modulator, with
CC CHUK/IKK-alpha and with IKBKB/IKK-beta (By similarity). Interacts with
CC TRAF6; this interaction is direct (PubMed:19825828). Interacts with
CC IL17RA and IL17RC (PubMed:19825828, PubMed:33723527). Interacts with
CC IL17RB (By similarity). {ECO:0000250|UniProtKB:O43734,
CC ECO:0000269|PubMed:19825828, ECO:0000269|PubMed:33723527}.
CC -!- INTERACTION:
CC Q8N7N6; Q9R0T8: Ikbke; NbExp=3; IntAct=EBI-646165, EBI-6664658;
CC Q8N7N6; P70191: Traf5; NbExp=3; IntAct=EBI-646165, EBI-523899;
CC Q8N7N6; P70196: Traf6; NbExp=4; IntAct=EBI-646165, EBI-448028;
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DR EMBL; AK037407; BAC29801.1; -; mRNA.
DR EMBL; AK052190; BAC34875.1; -; mRNA.
DR EMBL; AK098107; BAC05236.1; -; mRNA.
DR EMBL; JX869941; AFY98903.1; -; mRNA.
DR EMBL; AC160403; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096483; AAH96483.1; -; mRNA.
DR EMBL; BC138234; AAI38235.1; -; mRNA.
DR EMBL; BC138235; AAI38236.1; -; mRNA.
DR CCDS; CCDS23789.1; -.
DR RefSeq; NP_598761.2; NM_134000.3.
DR AlphaFoldDB; Q8N7N6; -.
DR IntAct; Q8N7N6; 8.
DR STRING; 10090.ENSMUSP00000019987; -.
DR PhosphoSitePlus; Q8N7N6; -.
DR EPD; Q8N7N6; -.
DR MaxQB; Q8N7N6; -.
DR PaxDb; Q8N7N6; -.
DR PRIDE; Q8N7N6; -.
DR ProteomicsDB; 332614; -.
DR Antibodypedia; 19327; 436 antibodies from 39 providers.
DR DNASU; 103213; -.
DR Ensembl; ENSMUST00000019987; ENSMUSP00000019987; ENSMUSG00000019842.
DR GeneID; 103213; -.
DR KEGG; mmu:103213; -.
DR UCSC; uc007ewa.1; mouse.
DR CTD; 10758; -.
DR MGI; MGI:2143599; Traf3ip2.
DR VEuPathDB; HostDB:ENSMUSG00000019842; -.
DR eggNOG; ENOG502QTXH; Eukaryota.
DR GeneTree; ENSGT00940000161944; -.
DR HOGENOM; CLU_036721_1_0_1; -.
DR InParanoid; Q8N7N6; -.
DR OMA; CMRVIRP; -.
DR PhylomeDB; Q8N7N6; -.
DR TreeFam; TF329063; -.
DR BioGRID-ORCS; 103213; 6 hits in 72 CRISPR screens.
DR ChiTaRS; Traf3ip2; mouse.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8N7N6; protein.
DR Bgee; ENSMUSG00000019842; Expressed in prostate gland ventral lobe and 193 other tissues.
DR GO; GO:0031410; C:cytoplasmic vesicle; IPI:MGI.
DR GO; GO:0005634; C:nucleus; IPI:MGI.
DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0002344; P:B cell affinity maturation; IMP:MGI.
DR GO; GO:0001783; P:B cell apoptotic process; IMP:MGI.
DR GO; GO:0001782; P:B cell homeostasis; IMP:MGI.
DR GO; GO:0019724; P:B cell mediated immunity; IGI:MGI.
DR GO; GO:0023035; P:CD40 signaling pathway; IGI:MGI.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IMP:MGI.
DR GO; GO:0097398; P:cellular response to interleukin-17; IDA:MGI.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IMP:MGI.
DR GO; GO:1990959; P:eosinophil homeostasis; IMP:MGI.
DR GO; GO:0002447; P:eosinophil mediated immunity; IMP:MGI.
DR GO; GO:0001768; P:establishment of T cell polarity; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IDA:MGI.
DR GO; GO:0007507; P:heart development; IDA:MGI.
DR GO; GO:0006959; P:humoral immune response; IMP:MGI.
DR GO; GO:0006955; P:immune response; IMP:MGI.
DR GO; GO:0006954; P:inflammatory response; IDA:MGI.
DR GO; GO:0097400; P:interleukin-17-mediated signaling pathway; IDA:MGI.
DR GO; GO:0038173; P:interleukin-17A-mediated signaling pathway; IDA:MGI.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0002269; P:leukocyte activation involved in inflammatory response; IMP:MGI.
DR GO; GO:0048535; P:lymph node development; IMP:MGI.
DR GO; GO:0048255; P:mRNA stabilization; IDA:MGI.
DR GO; GO:0070254; P:mucus secretion; IMP:MGI.
DR GO; GO:0042119; P:neutrophil activation; IMP:MGI.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; ISO:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0006606; P:protein import into nucleus; IDA:MGI.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISO:MGI.
DR GO; GO:0034504; P:protein localization to nucleus; IDA:MGI.
DR GO; GO:0110012; P:protein localization to P-body; IDA:MGI.
DR GO; GO:0000209; P:protein polyubiquitination; IMP:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IMP:MGI.
DR GO; GO:0034097; P:response to cytokine; IMP:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:MGI.
DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IDA:MGI.
DR GO; GO:0043588; P:skin development; IMP:MGI.
DR GO; GO:0048536; P:spleen development; IMP:MGI.
DR GO; GO:0042110; P:T cell activation; IMP:MGI.
DR GO; GO:0030217; P:T cell differentiation; IMP:MGI.
DR GO; GO:0072538; P:T-helper 17 type immune response; IDA:MGI.
DR GO; GO:0002334; P:transitional two stage B cell differentiation; IMP:MGI.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IGI:MGI.
DR GO; GO:0042092; P:type 2 immune response; IMP:MGI.
DR InterPro; IPR013568; SEFIR_dom.
DR Pfam; PF08357; SEFIR; 1.
DR PROSITE; PS51534; SEFIR; 1.
PE 1: Evidence at protein level;
KW Inflammatory response; Reference proteome; Transferase;
KW Ubl conjugation pathway.
FT CHAIN 1..555
FT /note="E3 ubiquitin ligase TRAF3IP2"
FT /id="PRO_0000450859"
FT DOMAIN 390..531
FT /note="SEFIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00867"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 82..189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 308..380
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 122..137
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 286
FT /note="L->G: Impairs IL17A-mediated signaling."
FT /evidence="ECO:0000269|PubMed:19825828"
SQ SEQUENCE 555 AA; 62440 MW; 54B40C8D81C3D827 CRC64;
MNRSIPVEVD ESEPFPSQLL KPIPEYSPEE ELEPPAPNTR NMAPSSLSVL QCPPLKLANH
QPVSQQVTCL RAKVLEEGEA SFFRRHPELG KDISSCSSGA SEPESELGAL PPEHRFTLTE
KRNRWLGSQL SAASPDTGHE SDKSDPSLPN ALADSFSGGQ EMMPRPRPRP GPHRHRAAPD
VPTIDTGYDS QPQDVLGIRQ LERPLPLTSS CYLQDLPGPL RSRELPPQFE LERYPMNAQL
LPPHPSPQAP WNCQYYCPGG PYHHQVPHGH GYPPAAAYQQ VLQPALPGQV LPGARARGPR
PVQKVILNDS SPQDQEERPA QRDFSFPRLP RDQLYRPPSN GVEAPEESLD LPAELRPHGP
QAPSLAAVPR PPSNPLARGT LRTSNLPEEL RKVFITYSMD TAMEVVKFVN FLLVNGFQTA
IDIFEDRIRG IDIIKWMERY LRDKTVMIIV AISPKYKQDV EGAESQLDED EHGLHTKYIH
RMMQIEFISQ GSMNFRFIPV LFPNAKKEHV PTWLQNTHVY SWPKNKKNIL LRLLREEEYV
APPRGPLPTL QVVPL
