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 27-MAR-2024, entry version 197. 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 INVOLVEMENT IN SUSCEPTIBILITY TO PSORS13, AND VARIANT 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}; 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; 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; 52. DR IntAct; O43734; 18. DR MINT; O43734; -. DR STRING; 9606.ENSP00000345984; -. DR ChEMBL; CHEMBL4523586; -. DR GlyConnect; 2015; 3 N-Linked glycans (1 site). DR GlyCosmos; O43734; 1 site, 6 glycans. 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; 9606-ENSP00000357750; -. DR PeptideAtlas; 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; 467 antibodies from 39 providers. DR DNASU; 10758; -. DR Ensembl; ENST00000340026.10; ENSP00000345984.6; ENSG00000056972.21. [O43734-1] DR Ensembl; ENST00000359831.8; ENSP00000352889.4; ENSG00000056972.21. [O43734-5] DR Ensembl; ENST00000368730.5; ENSP00000498323.1; ENSG00000056972.21. [O43734-4] DR Ensembl; ENST00000368734.5; ENSP00000498345.1; ENSG00000056972.21. [O43734-4] DR Ensembl; ENST00000368735.1; ENSP00000357724.1; ENSG00000056972.21. [O43734-4] DR Ensembl; ENST00000368761.11; ENSP00000357750.5; ENSG00000056972.21. [O43734-2] DR Ensembl; ENST00000651547.2; ENSP00000514681.1; ENSG00000056972.21. [O43734-2] 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 AGR; HGNC:1343; -. 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; QRYPVCA; -. DR OrthoDB; 2950388at2759; -. DR PhylomeDB; O43734; -. DR TreeFam; TF329063; -. DR PathwayCommons; O43734; -. DR SignaLink; O43734; -. DR SIGNOR; O43734; -. DR BioGRID-ORCS; 10758; 17 hits in 1157 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 178 other cell types or tissues. DR ExpressionAtlas; O43734; baseline and differential. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl. DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IC:UniProt. 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:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IEP:UniProtKB. DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IDA:CACAO. 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 Gene3D; 3.40.50.11530; -; 1. DR InterPro; IPR013568; SEFIR_dom. DR PANTHER; PTHR34257; ADAPTER PROTEIN CIKS; 1. DR PANTHER; PTHR34257:SF2; E3 UBIQUITIN LIGASE TRAF3IP2; 1. DR Pfam; PF08357; SEFIR; 1. DR PROSITE; PS51534; SEFIR; 1. DR Genevisible; O43734; HS. 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 (likely risk factor for PSORS13; there is a FT reducing binding of this variant to TRAF6; FT 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 FT SEFIR-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 //