CIKS_HUMAN
ID CIKS_HUMAN Reviewed; 574 AA.
AC O43734; B2RAY9; E1P555; Q5R3A3; Q7Z6Q1; Q7Z6Q2; Q7Z6Q3; Q9H5W2; Q9H6Y3;
AC Q9NS14; Q9UG72;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=E3 ubiquitin ligase TRAF3IP2 {ECO:0000303|PubMed:19825828};
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|HGNC:HGNC:1343};
GN Synonyms=C6orf2, C6orf4, C6orf5, C6orf6;
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] (ISOFORMS 1 AND 2).
RX PubMed=10903453; DOI=10.1016/s0378-1119(00)00231-6;
RA Morelli C., Magnanini C., Mungall A.J., Negrini M., Barbanti-Brodano G.;
RT "Cloning and characterization of two overlapping genes in a subregion at
RT 6q21 involved in replicative senescence and schizophrenia.";
RL Gene 252:217-225(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLN-332.
RC TISSUE=Embryonic kidney;
RX PubMed=10962024; DOI=10.1073/pnas.160265197;
RA Li X., Commane M., Nie H., Hua X., Chatterjee-Kishore M., Wald D., Haag M.,
RA Stark G.R.;
RT "Act1, an NF-kappa B-activating protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:10489-10493(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=10962033; DOI=10.1073/pnas.190245697;
RA Leonardi A., Chariot A., Claudio E., Cunningham K., Siebenlist U.;
RT "CIKS, a connection to Ikappa B kinase and stress-activated protein
RT kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:10494-10499(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 5), AND VARIANT
RP GLN-332.
RC TISSUE=Colon, and Kidney;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLN-332.
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLN-332.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4), AND VARIANT
RP GLN-332.
RC TISSUE=Lymph;
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 INTERACTION WITH TRAF6.
RX PubMed=12459498; DOI=10.1016/s0014-5793(02)03688-8;
RA Kanamori M., Kai C., Hayashizaki Y., Suzuki H.;
RT "NF-kappaB activator Act1 associates with IL-1/Toll pathway adapter
RT molecule TRAF6.";
RL FEBS Lett. 532:241-246(2002).
RN [10]
RP FUNCTION, MUTAGENESIS OF LEU-303; PRO-318; VAL-319 AND LEU-324, INTERACTION
RP WITH IL17RA AND TRAF6, AND CATALYTIC ACTIVITY.
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 [11]
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).
RN [12]
RP INVOLVEMENT IN SUSCEPTIBILITY TO PSORS13, VARIANT ASN-19, AND
RP CHARACTERIZATION OF VARIANT ASN-19.
RX PubMed=20953186; DOI=10.1038/ng.688;
RA Huffmeier U., Uebe S., Ekici A.B., Bowes J., Giardina E., Korendowych E.,
RA Juneblad K., Apel M., McManus R., Ho P., Bruce I.N., Ryan A.W., Behrens F.,
RA Lascorz J., Bohm B., Traupe H., Lohmann J., Gieger C., Wichmann H.E.,
RA Herold C., Steffens M., Klareskog L., Wienker T.F., Fitzgerald O.,
RA Alenius G.M., McHugh N.J., Novelli G., Burkhardt H., Barton A., Reis A.;
RT "Common variants at TRAF3IP2 are associated with susceptibility to
RT psoriatic arthritis and psoriasis.";
RL Nat. Genet. 42:996-999(2010).
RN [13]
RP VARIANT PSORS13 ASN-19.
RX PubMed=20953188; DOI=10.1038/ng.689;
RA Ellinghaus E., Ellinghaus D., Stuart P.E., Nair R.P., Debrus S.,
RA Raelson J.V., Belouchi M., Fournier H., Reinhard C., Ding J., Li Y.,
RA Tejasvi T., Gudjonsson J., Stoll S.W., Voorhees J.J., Lambert S.,
RA Weidinger S., Eberlein B., Kunz M., Rahman P., Gladman D.D., Gieger C.,
RA Wichmann H.E., Karlsen T.H., Mayr G., Albrecht M., Kabelitz D.,
RA Mrowietz U., Abecasis G.R., Elder J.T., Schreiber S., Weichenthal M.,
RA Franke A.;
RT "Genome-wide association study identifies a psoriasis susceptibility locus
RT at TRAF3IP2.";
RL Nat. Genet. 42:991-995(2010).
RN [14]
RP VARIANT CANDF8 ILE-536, CHARACTERIZATION OF VARIANT CANDF8 ILE-536,
RP FUNCTION, AND INTERACTION WITH IL17RA; IL17RB AND IL17RC.
RX PubMed=24120361; DOI=10.1016/j.immuni.2013.09.002;
RA Boisson B., Wang C., Pedergnana V., Wu L., Cypowyj S., Rybojad M.,
RA Belkadi A., Picard C., Abel L., Fieschi C., Puel A., Li X., Casanova J.L.;
RT "An ACT1 mutation selectively abolishes interleukin-17 responses in humans
RT with chronic mucocutaneous candidiasis.";
RL Immunity 39:676-686(2013).
CC -!- FUNCTION: E3 ubiquitin ligase that catalyzes 'Lys-63'-linked
CC polyubiquitination of target protein, enhancing protein-protein
CC interaction and cell signaling (PubMed:19825828). Transfers ubiquitin
CC from E2 ubiquitin-conjugating enzyme UBE2V1-UBE2N to substrate protein
CC (PubMed:19825828). Essential adapter molecule in IL17A-mediated
CC signaling (PubMed:19825828, PubMed:24120361). Upon IL17A stimulation,
CC interacts with IL17RA and IL17RC receptor chains through SEFIR domains
CC and catalyzes 'Lys-63'-linked polyubiquitination of TRAF6, leading to
CC TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways
CC (PubMed:19825828). {ECO:0000269|PubMed:19825828,
CC ECO:0000269|PubMed:24120361, 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 (PubMed:12459498). Interacts
CC with TRAF6; this interaction is direct (PubMed:12459498,
CC PubMed:19825828). Interacts with IL17RA and IL17RC (PubMed:19825828,
CC PubMed:24120361, PubMed:33723527). Interacts with IL17RB
CC (PubMed:24120361). {ECO:0000269|PubMed:12459498,
CC ECO:0000269|PubMed:19825828, ECO:0000269|PubMed:24120361,
CC ECO:0000269|PubMed:33723527}.
CC -!- INTERACTION:
CC O43734; Q96C98: FHL3; NbExp=3; IntAct=EBI-744798, EBI-10229248;
CC O43734; Q13084: MRPL28; NbExp=3; IntAct=EBI-744798, EBI-723426;
CC O43734; Q9UFD9: RIMBP3; NbExp=3; IntAct=EBI-744798, EBI-10182375;
CC O43734; O75716: STK16; NbExp=3; IntAct=EBI-744798, EBI-749295;
CC O43734; Q9Y4K3: TRAF6; NbExp=4; IntAct=EBI-744798, EBI-359276;
CC O43734; Q15654: TRIP6; NbExp=3; IntAct=EBI-744798, EBI-742327;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=C6ORF4;
CC IsoId=O43734-1; Sequence=Displayed;
CC Name=2; Synonyms=C6ORF5, C6ORF6;
CC IsoId=O43734-2; Sequence=VSP_004163;
CC Name=3;
CC IsoId=O43734-3; Sequence=VSP_035733;
CC Name=4;
CC IsoId=O43734-4; Sequence=VSP_040374;
CC Name=5;
CC IsoId=O43734-5; Sequence=VSP_004163, VSP_047098;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DISEASE: Psoriasis 13 (PSORS13) [MIM:614070]: A common, chronic
CC inflammatory disease of the skin with multifactorial etiology. It is
CC characterized by red, scaly plaques usually found on the scalp, elbows
CC and knees. These lesions are caused by abnormal keratinocyte
CC proliferation and infiltration of inflammatory cells into the dermis
CC and epidermis. {ECO:0000269|PubMed:20953186,
CC ECO:0000269|PubMed:20953188}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Candidiasis, familial, 8 (CANDF8) [MIM:615527]: A primary
CC immunodeficiency disorder with altered immune responses and impaired
CC clearance of fungal infections, selective against Candida. It is
CC characterized by persistent and/or recurrent infections of the skin,
CC nails and mucous membranes caused by organisms of the genus Candida,
CC mainly Candida albicans. {ECO:0000269|PubMed:24120361}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- CAUTION: The presence of U-box domain is not predicted by SMART and
CC SWISS-MODEL tools. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15507.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF136405; AAF67445.1; -; mRNA.
DR EMBL; AF136406; AAF67446.1; -; mRNA.
DR EMBL; AF136407; AAF67447.1; -; mRNA.
DR EMBL; AF274303; AAG15367.1; -; mRNA.
DR EMBL; AF272151; AAG15407.1; -; mRNA.
DR EMBL; AK025351; BAB15117.1; -; mRNA.
DR EMBL; AK026602; BAB15507.1; ALT_INIT; mRNA.
DR EMBL; AK314415; BAG37036.1; -; mRNA.
DR EMBL; AL050289; CAB43390.1; -; mRNA.
DR EMBL; AL008730; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z97989; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48285.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW48287.1; -; Genomic_DNA.
DR EMBL; BC002823; AAH02823.1; -; mRNA.
DR EMBL; BI856094; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS5092.1; -. [O43734-1]
DR CCDS; CCDS5093.1; -. [O43734-2]
DR CCDS; CCDS55049.1; -. [O43734-4]
DR CCDS; CCDS55050.1; -. [O43734-5]
DR PIR; T08794; T08794.
DR RefSeq; NP_001157753.1; NM_001164281.2. [O43734-5]
DR RefSeq; NP_001157755.1; NM_001164283.2. [O43734-4]
DR RefSeq; NP_671733.2; NM_147200.2. [O43734-1]
DR RefSeq; NP_679211.2; NM_147686.3. [O43734-2]
DR RefSeq; XP_006715382.1; XM_006715319.3.
DR RefSeq; XP_011533688.1; XM_011535386.1.
DR AlphaFoldDB; O43734; -.
DR SMR; O43734; -.
DR BioGRID; 115979; 50.
DR IntAct; O43734; 18.
DR MINT; O43734; -.
DR STRING; 9606.ENSP00000357750; -.
DR ChEMBL; CHEMBL4523586; -.
DR GlyConnect; 2015; 3 N-Linked glycans (1 site).
DR GlyGen; O43734; 1 site, 6 N-linked glycans (1 site).
DR iPTMnet; O43734; -.
DR PhosphoSitePlus; O43734; -.
DR BioMuta; TRAF3IP2; -.
DR EPD; O43734; -.
DR jPOST; O43734; -.
DR MassIVE; O43734; -.
DR MaxQB; O43734; -.
DR PaxDb; O43734; -.
DR PeptideAtlas; O43734; -.
DR PRIDE; O43734; -.
DR ProteomicsDB; 49136; -. [O43734-1]
DR ProteomicsDB; 49137; -. [O43734-2]
DR ProteomicsDB; 49138; -. [O43734-3]
DR ProteomicsDB; 49139; -. [O43734-4]
DR ProteomicsDB; 69454; -.
DR Antibodypedia; 19327; 436 antibodies from 39 providers.
DR DNASU; 10758; -.
DR Ensembl; ENST00000340026.10; ENSP00000345984.6; ENSG00000056972.20. [O43734-1]
DR Ensembl; ENST00000359831.8; ENSP00000352889.4; ENSG00000056972.20. [O43734-5]
DR Ensembl; ENST00000368730.5; ENSP00000498323.1; ENSG00000056972.20. [O43734-4]
DR Ensembl; ENST00000368734.5; ENSP00000498345.1; ENSG00000056972.20. [O43734-4]
DR Ensembl; ENST00000368735.1; ENSP00000357724.1; ENSG00000056972.20. [O43734-4]
DR Ensembl; ENST00000368761.11; ENSP00000357750.5; ENSG00000056972.20. [O43734-2]
DR Ensembl; ENST00000392556.8; ENSP00000376339.5; ENSG00000056972.20. [O43734-1]
DR GeneID; 10758; -.
DR KEGG; hsa:10758; -.
DR MANE-Select; ENST00000368761.11; ENSP00000357750.5; NM_147686.4; NP_679211.2. [O43734-2]
DR UCSC; uc003pvf.5; human. [O43734-1]
DR CTD; 10758; -.
DR DisGeNET; 10758; -.
DR GeneCards; TRAF3IP2; -.
DR HGNC; HGNC:1343; TRAF3IP2.
DR HPA; ENSG00000056972; Low tissue specificity.
DR MalaCards; TRAF3IP2; -.
DR MIM; 607043; gene.
DR MIM; 614070; phenotype.
DR MIM; 615527; phenotype.
DR neXtProt; NX_O43734; -.
DR OpenTargets; ENSG00000056972; -.
DR Orphanet; 1334; Chronic mucocutaneous candidiasis.
DR PharmGKB; PA25938; -.
DR VEuPathDB; HostDB:ENSG00000056972; -.
DR eggNOG; ENOG502QTXH; Eukaryota.
DR GeneTree; ENSGT00940000161944; -.
DR HOGENOM; CLU_036721_1_0_1; -.
DR InParanoid; O43734; -.
DR OMA; CMRVIRP; -.
DR OrthoDB; 1353706at2759; -.
DR PhylomeDB; O43734; -.
DR TreeFam; TF329063; -.
DR PathwayCommons; O43734; -.
DR SignaLink; O43734; -.
DR SIGNOR; O43734; -.
DR BioGRID-ORCS; 10758; 11 hits in 1071 CRISPR screens.
DR ChiTaRS; TRAF3IP2; human.
DR GeneWiki; TRAF3IP2; -.
DR GenomeRNAi; 10758; -.
DR Pharos; O43734; Tbio.
DR PRO; PR:O43734; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O43734; protein.
DR Bgee; ENSG00000056972; Expressed in cartilage tissue and 176 other tissues.
DR ExpressionAtlas; O43734; baseline and differential.
DR Genevisible; O43734; HS.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005102; F:signaling receptor binding; IEA:Ensembl.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0002344; P:B cell affinity maturation; IEA:Ensembl.
DR GO; GO:0001783; P:B cell apoptotic process; IEA:Ensembl.
DR GO; GO:0001782; P:B cell homeostasis; IEA:Ensembl.
DR GO; GO:0023035; P:CD40 signaling pathway; IEA:Ensembl.
DR GO; GO:1990959; P:eosinophil homeostasis; IEA:Ensembl.
DR GO; GO:0002447; P:eosinophil mediated immunity; IEA:Ensembl.
DR GO; GO:0001768; P:establishment of T cell polarity; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0006959; P:humoral immune response; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IDA:MGI.
DR GO; GO:0097400; P:interleukin-17-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0038173; P:interleukin-17A-mediated signaling pathway; IDA:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; NAS:UniProtKB.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0002269; P:leukocyte activation involved in inflammatory response; IEA:Ensembl.
DR GO; GO:0048535; P:lymph node development; IEA:Ensembl.
DR GO; GO:0048255; P:mRNA stabilization; IEA:Ensembl.
DR GO; GO:0070254; P:mucus secretion; IEA:Ensembl.
DR GO; GO:0042119; P:neutrophil activation; IEA:Ensembl.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IDA:CACAO.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEP:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0110012; P:protein localization to P-body; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IEA:Ensembl.
DR GO; GO:0043588; P:skin development; IEA:Ensembl.
DR GO; GO:0048536; P:spleen development; IEA:Ensembl.
DR GO; GO:0030217; P:T cell differentiation; IEA:Ensembl.
DR GO; GO:0072538; P:T-helper 17 type immune response; IEA:Ensembl.
DR GO; GO:0002334; P:transitional two stage B cell differentiation; IEA:Ensembl.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0042092; P:type 2 immune response; IEA:Ensembl.
DR InterPro; IPR013568; SEFIR_dom.
DR Pfam; PF08357; SEFIR; 1.
DR PROSITE; PS51534; SEFIR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Inflammatory response;
KW Reference proteome; Transferase; Ubl conjugation pathway.
FT CHAIN 1..574
FT /note="E3 ubiquitin ligase TRAF3IP2"
FT /id="PRO_0000089751"
FT DOMAIN 409..550
FT /note="SEFIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00867"
FT REGION 1..256
FT /note="Mediates interaction with TRAF6"
FT /evidence="ECO:0000269|PubMed:12459498"
FT REGION 1..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 155..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 327..403
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..67
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 168..190
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 375..395
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..465
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040374"
FT VAR_SEQ 1..421
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_035733"
FT VAR_SEQ 1..9
FT /note="Missing (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:10903453,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_004163"
FT VAR_SEQ 463
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047098"
FT VARIANT 19
FT /note="D -> N (in PSORS13; there is a reducing binding of
FT this variant to TRAF6; dbSNP:rs33980500)"
FT /evidence="ECO:0000269|PubMed:20953186,
FT ECO:0000269|PubMed:20953188"
FT /id="VAR_047349"
FT VARIANT 83
FT /note="R -> W (in dbSNP:rs13190932)"
FT /id="VAR_031227"
FT VARIANT 332
FT /note="H -> Q (in dbSNP:rs1043730)"
FT /evidence="ECO:0000269|PubMed:10962024,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005, ECO:0000269|Ref.7"
FT /id="VAR_024307"
FT VARIANT 536
FT /note="T -> I (in CANDF8; abolishes homotypic interactions
FT with the SEFIR domain of IL17RA, IL17RB and IL17RC; does
FT not affect homodimerization; does not affect SEFIR-
FT independent interactions with other proteins;
FT dbSNP:rs397518485)"
FT /evidence="ECO:0000269|PubMed:24120361"
FT /id="VAR_070904"
FT MUTAGEN 303
FT /note="L->G: Loss of E3 ubiquitin ligase activity."
FT /evidence="ECO:0000269|PubMed:19825828"
FT MUTAGEN 318
FT /note="P->G: Decreases E3 ubiquitin ligase activity."
FT /evidence="ECO:0000269|PubMed:19825828"
FT MUTAGEN 319
FT /note="V->R: Loss of E3 ubiquitin ligase activity."
FT /evidence="ECO:0000269|PubMed:19825828"
FT MUTAGEN 324
FT /note="L->R: Decreases E3 ubiquitin ligase activity."
FT /evidence="ECO:0000269|PubMed:19825828"
FT CONFLICT 334
FT /note="E -> D (in Ref. 3; AAG15407)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="P -> S (in Ref. 1; AAF67447)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 574 AA; 64666 MW; 4985795466D71422 CRC64;
MPPQLQETRM NRSIPVEVDE SEPYPSQLLK PIPEYSPEEE SEPPAPNIRN MAPNSLSAPT
MLHNSSGDFS QAHSTLKLAN HQRPVSRQVT CLRTQVLEDS EDSFCRRHPG LGKAFPSGCS
AVSEPASESV VGALPAEHQF SFMEKRNQWL VSQLSAASPD TGHDSDKSDQ SLPNASADSL
GGSQEMVQRP QPHRNRAGLD LPTIDTGYDS QPQDVLGIRQ LERPLPLTSV CYPQDLPRPL
RSREFPQFEP QRYPACAQML PPNLSPHAPW NYHYHCPGSP DHQVPYGHDY PRAAYQQVIQ
PALPGQPLPG ASVRGLHPVQ KVILNYPSPW DHEERPAQRD CSFPGLPRHQ DQPHHQPPNR
AGAPGESLEC PAELRPQVPQ PPSPAAVPRP PSNPPARGTL KTSNLPEELR KVFITYSMDT
AMEVVKFVNF LLVNGFQTAI DIFEDRIRGI DIIKWMERYL RDKTVMIIVA ISPKYKQDVE
GAESQLDEDE HGLHTKYIHR MMQIEFIKQG SMNFRFIPVL FPNAKKEHVP TWLQNTHVYS
WPKNKKNILL RLLREEEYVA PPRGPLPTLQ VVPL
