Full text data of TRAF3IP2
TRAF3IP2
(C6orf2, C6orf4, C6orf5, C6orf6)
[Confidence: low (only semi-automatic identification from reviews)]
Adapter protein CIKS (Connection to IKK and SAPK/JNK; Nuclear factor NF-kappa-B activator 1; ACT1; TRAF3-interacting protein 2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Adapter protein CIKS (Connection to IKK and SAPK/JNK; Nuclear factor NF-kappa-B activator 1; ACT1; TRAF3-interacting protein 2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O43734
ID CIKS_HUMAN Reviewed; 574 AA.
AC O43734; B2RAY9; E1P555; Q5R3A3; Q7Z6Q1; Q7Z6Q2; Q7Z6Q3; Q9H5W2;
read moreAC Q9H6Y3; Q9NS14; Q9UG72;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 22-JAN-2014, entry version 123.
DE RecName: Full=Adapter protein CIKS;
DE AltName: Full=Connection to IKK and SAPK/JNK;
DE AltName: Full=Nuclear factor NF-kappa-B activator 1;
DE Short=ACT1;
DE AltName: Full=TRAF3-interacting protein 2;
GN Name=TRAF3IP2; Synonyms=C6orf2, C6orf4, C6orf5, C6orf6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Barbanti-Brodano G.;
RT "Cloning and characterization of two overlapping genes in a subregion
RT at 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.,
RA Haag M., 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
RP VARIANT 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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
RP 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA 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.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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 adaptor
RT molecule TRAF6.";
RL FEBS Lett. 532:241-246(2002).
RN [10]
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.,
RA Korendowych E., Juneblad K., Apel M., McManus R., Ho P., Bruce I.N.,
RA Ryan A.W., Behrens F., Lascorz J., Bohm B., Traupe H., Lohmann J.,
RA Gieger C., Wichmann H.E., Herold C., Steffens M., Klareskog L.,
RA Wienker T.F., Fitzgerald O., Alenius G.M., McHugh N.J., Novelli G.,
RA 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 [11]
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.,
RA Gieger C., Wichmann H.E., Karlsen T.H., Mayr G., Albrecht M.,
RA Kabelitz D., Mrowietz U., Abecasis G.R., Elder J.T., Schreiber S.,
RA Weichenthal M., Franke A.;
RT "Genome-wide association study identifies a psoriasis susceptibility
RT locus at TRAF3IP2.";
RL Nat. Genet. 42:991-995(2010).
CC -!- FUNCTION: Could be involved in the activation of both NF-kappa-B
CC via a NF-kappa-B inhibitor kinase (IKK)-dependent mechanism and
CC stress-activated protein kinase (SAPK)/JNK.
CC -!- SUBUNIT: Interacts with IKBKG/NF-kappa B essential modulator, with
CC CHUK/IKK-alpha and with IKBKB/IKK-beta. Interacts with TRAF6.
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 Note=No experimental confirmation available;
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
CC is characterized by red, scaly plaques usually found on the scalp,
CC elbows and knees. These lesions are caused by abnormal
CC keratinocyte proliferation and infiltration of inflammatory cells
CC into the dermis and epidermis. Note=Disease susceptibility is
CC associated with variations affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Contains 1 SEFIR domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15507.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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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; CAA15506.1; -; Genomic_DNA.
DR EMBL; AL008730; CAA15507.1; -; Genomic_DNA.
DR EMBL; AL008730; CAD92596.1; -; Genomic_DNA.
DR EMBL; AL008730; CAD92597.1; -; Genomic_DNA.
DR EMBL; Z97989; CAD92597.1; JOINED; Genomic_DNA.
DR EMBL; Z97989; CAI22298.1; -; Genomic_DNA.
DR EMBL; AL008730; CAI22298.1; JOINED; Genomic_DNA.
DR EMBL; Z97989; CAI22297.1; -; Genomic_DNA.
DR EMBL; AL008730; CAI22297.1; JOINED; 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 PIR; T08794; T08794.
DR RefSeq; NP_001157753.1; NM_001164281.2.
DR RefSeq; NP_001157755.1; NM_001164283.2.
DR RefSeq; NP_679211.2; NM_147686.3.
DR UniGene; Hs.561514; -.
DR UniGene; Hs.740602; -.
DR ProteinModelPortal; O43734; -.
DR IntAct; O43734; 7.
DR MINT; MINT-143208; -.
DR STRING; 9606.ENSP00000345984; -.
DR PhosphoSite; O43734; -.
DR PaxDb; O43734; -.
DR PRIDE; O43734; -.
DR DNASU; 10758; -.
DR Ensembl; ENST00000340026; ENSP00000345984; ENSG00000056972.
DR Ensembl; ENST00000359831; ENSP00000352889; ENSG00000056972.
DR Ensembl; ENST00000368735; ENSP00000357724; ENSG00000056972.
DR Ensembl; ENST00000368761; ENSP00000357750; ENSG00000056972.
DR Ensembl; ENST00000392556; ENSP00000376339; ENSG00000056972.
DR GeneID; 10758; -.
DR KEGG; hsa:10758; -.
DR UCSC; uc003pvf.4; human.
DR CTD; 10758; -.
DR GeneCards; GC06M111877; -.
DR HGNC; HGNC:1343; TRAF3IP2.
DR HPA; HPA036352; -.
DR MIM; 607043; gene.
DR MIM; 614070; phenotype.
DR neXtProt; NX_O43734; -.
DR PharmGKB; PA25938; -.
DR eggNOG; NOG43147; -.
DR HOVERGEN; HBG002060; -.
DR InParanoid; O43734; -.
DR OMA; NYPSPWD; -.
DR OrthoDB; EOG7DVD9N; -.
DR PhylomeDB; O43734; -.
DR SignaLink; O43734; -.
DR GeneWiki; TRAF3IP2; -.
DR GenomeRNAi; 10758; -.
DR NextBio; 40857; -.
DR PRO; PR:O43734; -.
DR ArrayExpress; O43734; -.
DR Bgee; O43734; -.
DR CleanEx; HS_TRAF3IP2; -.
DR Genevestigator; O43734; -.
DR GO; GO:0001783; P:B cell apoptotic process; IEA:Ensembl.
DR GO; GO:0006959; P:humoral immune response; IEA:Ensembl.
DR GO; GO:0048305; P:immunoglobulin secretion; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; NAS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IEP:UniProtKB.
DR InterPro; IPR013568; SEFIR.
DR Pfam; PF08357; SEFIR; 1.
DR PROSITE; PS51534; SEFIR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Polymorphism;
KW Reference proteome.
FT CHAIN 1 574 Adapter protein CIKS.
FT /FTId=PRO_0000089751.
FT DOMAIN 409 550 SEFIR.
FT REGION 1 256 Mediates interaction with TRAF6.
FT VAR_SEQ 1 465 Missing (in isoform 4).
FT /FTId=VSP_040374.
FT VAR_SEQ 1 421 Missing (in isoform 3).
FT /FTId=VSP_035733.
FT VAR_SEQ 1 9 Missing (in isoform 2 and isoform 5).
FT /FTId=VSP_004163.
FT VAR_SEQ 463 463 Missing (in isoform 5).
FT /FTId=VSP_047098.
FT VARIANT 19 19 D -> N (in PSORS13; there is a reducing
FT binding of this variant to TRAF6;
FT dbSNP:rs33980500).
FT /FTId=VAR_047349.
FT VARIANT 83 83 R -> W (in dbSNP:rs13190932).
FT /FTId=VAR_031227.
FT VARIANT 332 332 H -> Q (in dbSNP:rs1043730).
FT /FTId=VAR_024307.
FT CONFLICT 334 334 E -> D (in Ref. 3; AAG15407).
FT CONFLICT 347 347 P -> S (in Ref. 1; AAF67447).
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
//
ID CIKS_HUMAN Reviewed; 574 AA.
AC O43734; B2RAY9; E1P555; Q5R3A3; Q7Z6Q1; Q7Z6Q2; Q7Z6Q3; Q9H5W2;
read moreAC Q9H6Y3; Q9NS14; Q9UG72;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 22-JAN-2014, entry version 123.
DE RecName: Full=Adapter protein CIKS;
DE AltName: Full=Connection to IKK and SAPK/JNK;
DE AltName: Full=Nuclear factor NF-kappa-B activator 1;
DE Short=ACT1;
DE AltName: Full=TRAF3-interacting protein 2;
GN Name=TRAF3IP2; Synonyms=C6orf2, C6orf4, C6orf5, C6orf6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Barbanti-Brodano G.;
RT "Cloning and characterization of two overlapping genes in a subregion
RT at 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.,
RA Haag M., 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
RP VARIANT 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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
RP 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA 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.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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 adaptor
RT molecule TRAF6.";
RL FEBS Lett. 532:241-246(2002).
RN [10]
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.,
RA Korendowych E., Juneblad K., Apel M., McManus R., Ho P., Bruce I.N.,
RA Ryan A.W., Behrens F., Lascorz J., Bohm B., Traupe H., Lohmann J.,
RA Gieger C., Wichmann H.E., Herold C., Steffens M., Klareskog L.,
RA Wienker T.F., Fitzgerald O., Alenius G.M., McHugh N.J., Novelli G.,
RA 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 [11]
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.,
RA Gieger C., Wichmann H.E., Karlsen T.H., Mayr G., Albrecht M.,
RA Kabelitz D., Mrowietz U., Abecasis G.R., Elder J.T., Schreiber S.,
RA Weichenthal M., Franke A.;
RT "Genome-wide association study identifies a psoriasis susceptibility
RT locus at TRAF3IP2.";
RL Nat. Genet. 42:991-995(2010).
CC -!- FUNCTION: Could be involved in the activation of both NF-kappa-B
CC via a NF-kappa-B inhibitor kinase (IKK)-dependent mechanism and
CC stress-activated protein kinase (SAPK)/JNK.
CC -!- SUBUNIT: Interacts with IKBKG/NF-kappa B essential modulator, with
CC CHUK/IKK-alpha and with IKBKB/IKK-beta. Interacts with TRAF6.
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 Note=No experimental confirmation available;
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
CC is characterized by red, scaly plaques usually found on the scalp,
CC elbows and knees. These lesions are caused by abnormal
CC keratinocyte proliferation and infiltration of inflammatory cells
CC into the dermis and epidermis. Note=Disease susceptibility is
CC associated with variations affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Contains 1 SEFIR domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15507.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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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; CAA15506.1; -; Genomic_DNA.
DR EMBL; AL008730; CAA15507.1; -; Genomic_DNA.
DR EMBL; AL008730; CAD92596.1; -; Genomic_DNA.
DR EMBL; AL008730; CAD92597.1; -; Genomic_DNA.
DR EMBL; Z97989; CAD92597.1; JOINED; Genomic_DNA.
DR EMBL; Z97989; CAI22298.1; -; Genomic_DNA.
DR EMBL; AL008730; CAI22298.1; JOINED; Genomic_DNA.
DR EMBL; Z97989; CAI22297.1; -; Genomic_DNA.
DR EMBL; AL008730; CAI22297.1; JOINED; 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 PIR; T08794; T08794.
DR RefSeq; NP_001157753.1; NM_001164281.2.
DR RefSeq; NP_001157755.1; NM_001164283.2.
DR RefSeq; NP_679211.2; NM_147686.3.
DR UniGene; Hs.561514; -.
DR UniGene; Hs.740602; -.
DR ProteinModelPortal; O43734; -.
DR IntAct; O43734; 7.
DR MINT; MINT-143208; -.
DR STRING; 9606.ENSP00000345984; -.
DR PhosphoSite; O43734; -.
DR PaxDb; O43734; -.
DR PRIDE; O43734; -.
DR DNASU; 10758; -.
DR Ensembl; ENST00000340026; ENSP00000345984; ENSG00000056972.
DR Ensembl; ENST00000359831; ENSP00000352889; ENSG00000056972.
DR Ensembl; ENST00000368735; ENSP00000357724; ENSG00000056972.
DR Ensembl; ENST00000368761; ENSP00000357750; ENSG00000056972.
DR Ensembl; ENST00000392556; ENSP00000376339; ENSG00000056972.
DR GeneID; 10758; -.
DR KEGG; hsa:10758; -.
DR UCSC; uc003pvf.4; human.
DR CTD; 10758; -.
DR GeneCards; GC06M111877; -.
DR HGNC; HGNC:1343; TRAF3IP2.
DR HPA; HPA036352; -.
DR MIM; 607043; gene.
DR MIM; 614070; phenotype.
DR neXtProt; NX_O43734; -.
DR PharmGKB; PA25938; -.
DR eggNOG; NOG43147; -.
DR HOVERGEN; HBG002060; -.
DR InParanoid; O43734; -.
DR OMA; NYPSPWD; -.
DR OrthoDB; EOG7DVD9N; -.
DR PhylomeDB; O43734; -.
DR SignaLink; O43734; -.
DR GeneWiki; TRAF3IP2; -.
DR GenomeRNAi; 10758; -.
DR NextBio; 40857; -.
DR PRO; PR:O43734; -.
DR ArrayExpress; O43734; -.
DR Bgee; O43734; -.
DR CleanEx; HS_TRAF3IP2; -.
DR Genevestigator; O43734; -.
DR GO; GO:0001783; P:B cell apoptotic process; IEA:Ensembl.
DR GO; GO:0006959; P:humoral immune response; IEA:Ensembl.
DR GO; GO:0048305; P:immunoglobulin secretion; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; NAS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IEP:UniProtKB.
DR InterPro; IPR013568; SEFIR.
DR Pfam; PF08357; SEFIR; 1.
DR PROSITE; PS51534; SEFIR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Polymorphism;
KW Reference proteome.
FT CHAIN 1 574 Adapter protein CIKS.
FT /FTId=PRO_0000089751.
FT DOMAIN 409 550 SEFIR.
FT REGION 1 256 Mediates interaction with TRAF6.
FT VAR_SEQ 1 465 Missing (in isoform 4).
FT /FTId=VSP_040374.
FT VAR_SEQ 1 421 Missing (in isoform 3).
FT /FTId=VSP_035733.
FT VAR_SEQ 1 9 Missing (in isoform 2 and isoform 5).
FT /FTId=VSP_004163.
FT VAR_SEQ 463 463 Missing (in isoform 5).
FT /FTId=VSP_047098.
FT VARIANT 19 19 D -> N (in PSORS13; there is a reducing
FT binding of this variant to TRAF6;
FT dbSNP:rs33980500).
FT /FTId=VAR_047349.
FT VARIANT 83 83 R -> W (in dbSNP:rs13190932).
FT /FTId=VAR_031227.
FT VARIANT 332 332 H -> Q (in dbSNP:rs1043730).
FT /FTId=VAR_024307.
FT CONFLICT 334 334 E -> D (in Ref. 3; AAG15407).
FT CONFLICT 347 347 P -> S (in Ref. 1; AAF67447).
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
//
MIM
607043
*RECORD*
*FIELD* NO
607043
*FIELD* TI
*607043 TRAF3-INTERACTING PROTEIN 2; TRAF3IP2
;;CHROMOSOME 6 OPEN READING FRAME 5; C6ORF5;;
read moreNUCLEAR FACTOR KAPPA-B ACTIVATOR 1; ACT1;;
CONNECTION TO I-KAPPA-B KINASE AND STRESS-ACTIVATED PROTEIN KINASE;
CIKS;;
CHROMOSOME 6 OPEN READING FRAME 4; C6ORF4;;
CHROMOSOME 6 OPEN READING FRAME 6; C6ORF6
*FIELD* TX
CLONING
Using mouse Nemo/Ikk-gamma (IKBKG; 300248) as bait in a yeast 2-hybrid
screen, Leonardi et al. (2000) cloned CIKS from a human liver cDNA
library. The deduced 574-amino acid protein contains a C-terminal
leucine zipper. Northern blot analysis of multiple human tissues
indicated ubiquitous expression of a 2.5-kb transcript.
Li et al. (2000) cloned a cDNA encoding ACT1 from a cDNA library
constructed from embryonic kidney cells induced to display constitutive
activation of nuclear factor kappa-B (NFKB; see 164011). The deduced
574-amino acid protein has a calculated molecular mass of 60 kD and
contains a helix-loop-helix domain and a C-terminal coiled-coil domain.
The helix-loop-helix domain shares 35% identity with the
helix-loop-helix domain of upstream stimulatory factor-1 (USF1; 191523).
Northern blot analysis detected highest expression in thymus, kidney,
and placenta, moderate expression in heart, skeletal muscle, colon,
liver, lung, and small intestine, and low expression in brain, spleen,
and peripheral blood leukocytes.
By screening thymus, skeletal muscle, and fetal liver cDNA libraries,
Morelli et al. (2000) identified 3 isoforms of ACT1 that they designated
C6ORF4, C6ORF5, and C6ORF6. C6ORF4 encodes a deduced 575-amino acid
protein. C6ORF5 and C6ORF6 result from the skipping of exon 2 and are
differentiated by use of alternate polyadenylation signals, yielding
identical proteins of 566 amino acids. Northern blot analysis detected
5.0- and 2.5-kb transcripts in all tissues examined, with a weak 3.8-kb
transcript in heart, skeletal muscle, and pancreas.
GENE FUNCTION
Leonardi et al. (2000) verified the interaction between CIKS and
IKK-gamma by in vitro binding assays using recombinant proteins and by
coimmunoprecipitation of lysates of transfected HeLa cells or
untransfected Jurkat T-leukemic cells. IKK-alpha (CHUK; 600664) and
IKK-beta (IKBKB; 603258) also coimmunoprecipitated with CIKS. Using
truncation mutants, the authors localized the binding domain to the N
terminus of CIKS. HeLa cells transfected with increasing amounts of CIKS
showed dose-dependent activation of an Ig kappa-B luciferase reporter
plasmid, and the activation could be blocked by cotransfection with
IKK-gamma. Cotransfection of CIKS with kinase-deficient mutants of NIK
(MAP3K14; 604655), MEKK1 (MAP3K1: 600982), IKK-alpha, and IKK-beta
indicated that CIKS activates NFKB exclusively through an IKK-dependent
mechanism. Overexpressed CIKS also potently activated SAPK/JNK (MAPK8;
601158). Analysis of the binding activity of truncation mutants showed
that the C terminus of CIK is involved in SAPK/JNK activation, whereas
the N terminus is necessary and sufficient for kappa-B reporter
activation.
Using gel shift assays, Li et al. (2000) confirmed constitutive
activation of NFKB with transfection of ACT1 into human embryonic kidney
cells. They also found constitutive activation of JNK and IKK.
Disruption of the N-terminal helix-loop-helix domain of ACT1 completely
abolished the interaction between ACT1 and the IKK complex as well as
the activation of NFKB.
By mutation analysis, Pacifico et al. (2003) identified a sequence in
the 5-prime flanking region of human CIKS that was essential for basal
promoter activity in a canine kidney cell line. RT-PCR, Northern, and
Western blot analyses showed that various proinflammatory cytokines
upregulated CIKS expression in HeLa cells.
Using immunoprecipitation analysis, Qian et al. (2007) found that IL17
(603149) induced association of ACT1 with IL17RA (605461) in various
cell types. The ACT1-IL17RA interaction required the SEFIR domain of
IL17RA. Expression of Il17-dependent inflammation-related genes was
abolished in Act1-deficient mouse cells. Mice lacking Act1 had delayed
onset and lower severity of experimental allergic encephalomyelitis, as
well as limited colitis. Qian et al. (2007) concluded that ACT1 is
essential for IL17-dependent signaling in autoimmune and inflammatory
disease.
GENE STRUCTURE
Morelli et al. (2000) determined that the ACT1 gene contains 10 exons
and spans more than 50 kb. They also identified C6UAS, which overlaps
exon 2 and is transcribed in the antisense orientation from the
complementary strand of C6ORF4. C6UAS has no apparent open reading
frame, but Morelli et al. (2000) provided experimental evidence that it
has a regulatory function and can behave as an antisense RNA in the
control of C6ORF4 translation.
Pacifico et al. (2003) mapped the CIKS transcription start site and
found that the 5-prime flanking region was TATA-less, but it had
initiator, GC, and CAAT boxes.
BIOCHEMICAL FEATURES
Zhang et al. (2013) reported the structure of the IL17RB SEFIR (for
'similar expression to FGFR and IL17R;' see 136350) domain at
1.8-angstrom resolution. SEFIR displays a 5-stranded parallel beta-sheet
that is wrapped by 6 helices. Site-directed mutagenesis analysis
identified helix alphaC as being critical for interaction with ACT1
(TRAF3IP2; 607043) and IL17E (IL25; 605658) signaling. This helix is
also critical for ACT1 function and is conserved in IL17RA (605461) and
IL17RC (610925). Helix alphaB, on the other hand, is important for ACT1
homodimerization, suggesting that distinct motifs participate in binding
with different ligands. Zhang et al. (2013) proposed that the structure
helps to explain IL17R intracellular signaling and the mechanism for the
specificity of SEFIR versus the TIR (see TLR2, 603028) domain in their
respective signaling pathways.
MAPPING
Morelli et al. (2000) identified ACT1 within an EST clone that maps to
chromosome 6q21.
MOLECULAR GENETICS
- Psoriasis Susceptibility 13
Ellinghaus et al. (2010) and Huffmeier et al. (2010) independently
identified association of a coding single-nucleotide polymorphism (SNP),
dbSNP rs33980500 (607043.0001), in the TRAF3IP2 gene with psoriasis
susceptibility (PSORS13; 614070).
- Familial Candidiasis 8
In an affected brother and sister from a consanguineous Algerian family
with chronic mucocutaneous candidiasis (CANDF8; 615527), Boisson et al.
(2013) identified homozygosity for a missense mutation in the TRAF3IP2
gene (T536I; 607043.0002). Neither patient displayed psoriasis.
*FIELD* AV
.0001
PSORIASIS SUSCEPTIBILITY 13
TRAF3IP2, ASP19ASN (dbSNP rs33980500)
In a case-control genomewide association study of psoriasis
susceptibility (PSORS13; 614070), Ellinghaus et al. (2010) identified a
coding SNP, dbSNP rs33980500, in exon 2 of the TRAF3IP2 gene. A C-to-T
transition results in substitution of asn for asp at codon 19 (D19N).
This SNP was significantly associated with risk for psoriasis vulgaris
(P = 1.24 x 10(-16)) and psoriatic arthritis (P = 4.57 x 10(-12)).
In an independent case-control genomewide association study, Huffmeier
et al. (2010) found significant association of dbSNP rs33980500 with
psoriatic arthritis in a subset of cases and controls (P = 1.13 x
10(-20), OR = 1.95). Functional assays showed reducing binding of this
TRAF3IP2 variant to TRAF6 (602355), suggesting altered modulation of
immunoregulatory signals through altered TRAF interactions as a novel
and shared pathway for psoriatic arthritis and psoriasis vulgaris.
Huffmeier et al. (2010) referred to the amino acid change correlated
with this SNP as ASP10ASN.
Using fibroblasts from a healthy individual who was homozygous for the
D10N variant in TRAF3IP2, Boisson et al. (2013) observed a weak response
to stimulation with IL17A (603149) and low but detectable GRO-alpha
(155730) and IL6 (147620) induction. In addition, costimulation with
IL17A and TNFA (191160) was synergistic in this individual's cells.
Boisson et al. (2013) concluded that D10N is a hypomorphic, but not
null, allele for cellular responses to IL17A, alone or in combination
with TNFA.
.0002
CANDIDIASIS, FAMILIAL, 8 (1 family)
TRAF3IP2, THR536ILE
In an affected brother and sister from a consanguineous Algerian family
with chronic mucocutaneous candidiasis (CANDF8; 615527), Boisson et al.
(2013) identified homozygosity for a c.1607C-T transition in the
TRAF3IP2 gene, resulting in a thr536-to-ile (T536I) substitution at a
highly conserved residue in the C-terminal part of the SEFIR domain. The
mutation segregated with disease in the family and was not found in more
than 10,000 chromosomes or in the 1000 Genomes Project or dbSNP (build
135) databases. Neither of the affected sibs displayed psoriasis.
Functional analysis using patient fibroblasts and EBV-B cells
demonstrated that the T536I mutant abolishes homotypic interactions with
the SEFIR domain of IL17RA (605461), IL17RB (605458), and IL17RC
(610925), but does not affect homodimerization or SEFIR-independent ACT1
interactions with other proteins. Patient fibroblasts did not produce
IL6 (147620) in response to IL17A (603149) or IL17F (606496).
Stimulation of patient peripheral blood mononuclear cells with IL2
(147680) and/or IL17E (605658) resulted in production of IL5 (147850)
only in response to IL2, and there was no synergistic response to
costimulation. Flow cytometric analysis indicated that the patients had
higher proportions of IL17- and IL22 (605330)-producing cells but normal
levels of IFNG (147570)-producing cells, suggesting that responsiveness
to IL17 rather than production of the cytokine is critical for
protection from chronic mucocutaneous candidiasis.
*FIELD* RF
1. Boisson, B.; Wang, C.; Pedergnana, V.; Wu, L.; Cypowyj, S.; Rybojad,
M.; Belkadi, A.; Picard, C.; Abel, L.; Fieschi, C.; Puel, A.; Li,
X.; Casanova, J.-L.: An ACT1 mutation selectively abolishes interleukin-17
responses in humans with chronic mucocutaneous candidiasis. Immunity 39:
676-686, 2013.
2. Ellinghaus, E.; Ellinghaus, D.; Stuart, P. E.; Nair, R. P.; Debrus,
S.; Raelson, J. V.; Belouchi, M.; Fournier, H.; Reinhard, C.; Ding,
J.; Li, Y.; Tejasvi, T.; and 21 others: Genome-wide association
study identifies a psoriasis susceptibility locus at TRAF3IP2. Nature
Genet. 42: 991-995, 2010.
3. Huffmeier, U.; Uebe, S.; Ekici, A. B.; Bowes, J.; Giardina, E.;
Korendowych, E.; Juneblad, K.; Apel, M.; McManus, R.; Ho, P.; Bruce,
I. N.; Ryan, A. W.; and 18 others: Common variants at TRAF3IP2
are associated with susceptibility to psoriatic arthritis and psoriasis. Nature
Genet. 42: 996-999, 2010.
4. Leonardi, A.; Chariot, A.; Claudio, E.; Cunningham, K.; Siebenlist,
U.: CIKS, a connection to I-kappa-B kinase and stress-activated protein
kinase. Proc. Nat. Acad. Sci. 97: 10494-10499, 2000.
5. Li, X.; Commane, M.; Nie, H.; Hua, X.; Chatterjee-Kishore, M.;
Wald, D.; Haag, M.; Stark, G. R.: Act1, an NF-kappa-B-activating
protein. Proc. Nat. Acad. Sci. 97: 10489-10493, 2000.
6. Morelli, C.; Magnanini, C.; Mungall, A. J.; Negrini, M.; Barbanti-Brodano,
G.: Cloning and characterization of two overlapping genes in a subregion
at 6q21 involved in replicative senescence and schizophrenia. Gene 252:
217-225, 2000.
7. Pacifico, F.; Barone, C.; Mellone, S.; Di Jeso, B.; Consiglio,
E.; Formisano, S.; Vito, P.; Leonardi, A.: Promoter identification
of CIKS, a novel NF-kappa-B activating gene, and regulation of its
expression. Gene 307: 99-109, 2003.
8. Qian, Y.; Liu, C.; Hartupee, J.; Altuntas, C. Z.; Gulen, M. F.;
Jane-wit, D.; Xiao, J.; Lu, Y.; Giltiay, N.; Liu, J.; Kordula, T.;
Zhang, Q.-W.; Vallance, B.; Swaidani, S.; Aronica, M.; Tuohy, V. K.;
Hamilton, T.; Li, X.: The adaptor Act1 is required for interleukin
17-dependent signaling associated with autoimmune and inflammatory
disease. Nature Immun. 8: 247-256, 2007.
9. Zhang, B.; Liu, C.; Qian, W.; Han, Y.; Li, X.; Deng, J.: Crystal
structure of IL-17 receptor B SEFIR domain. J. Immun. 190: 2320-2326,
2013.
*FIELD* CN
Marla J. F. O'Neill - updated: 11/14/2013
Ada Hamosh - updated: 6/24/2011
Paul J. Converse - updated: 11/12/2007
*FIELD* CD
Patricia A. Hartz: 6/18/2002
*FIELD* ED
alopez: 11/15/2013
mcolton: 11/14/2013
alopez: 6/30/2011
terry: 6/24/2011
alopez: 12/19/2007
mgross: 11/12/2007
alopez: 8/7/2007
mgross: 6/19/2002
mgross: 6/18/2002
*RECORD*
*FIELD* NO
607043
*FIELD* TI
*607043 TRAF3-INTERACTING PROTEIN 2; TRAF3IP2
;;CHROMOSOME 6 OPEN READING FRAME 5; C6ORF5;;
read moreNUCLEAR FACTOR KAPPA-B ACTIVATOR 1; ACT1;;
CONNECTION TO I-KAPPA-B KINASE AND STRESS-ACTIVATED PROTEIN KINASE;
CIKS;;
CHROMOSOME 6 OPEN READING FRAME 4; C6ORF4;;
CHROMOSOME 6 OPEN READING FRAME 6; C6ORF6
*FIELD* TX
CLONING
Using mouse Nemo/Ikk-gamma (IKBKG; 300248) as bait in a yeast 2-hybrid
screen, Leonardi et al. (2000) cloned CIKS from a human liver cDNA
library. The deduced 574-amino acid protein contains a C-terminal
leucine zipper. Northern blot analysis of multiple human tissues
indicated ubiquitous expression of a 2.5-kb transcript.
Li et al. (2000) cloned a cDNA encoding ACT1 from a cDNA library
constructed from embryonic kidney cells induced to display constitutive
activation of nuclear factor kappa-B (NFKB; see 164011). The deduced
574-amino acid protein has a calculated molecular mass of 60 kD and
contains a helix-loop-helix domain and a C-terminal coiled-coil domain.
The helix-loop-helix domain shares 35% identity with the
helix-loop-helix domain of upstream stimulatory factor-1 (USF1; 191523).
Northern blot analysis detected highest expression in thymus, kidney,
and placenta, moderate expression in heart, skeletal muscle, colon,
liver, lung, and small intestine, and low expression in brain, spleen,
and peripheral blood leukocytes.
By screening thymus, skeletal muscle, and fetal liver cDNA libraries,
Morelli et al. (2000) identified 3 isoforms of ACT1 that they designated
C6ORF4, C6ORF5, and C6ORF6. C6ORF4 encodes a deduced 575-amino acid
protein. C6ORF5 and C6ORF6 result from the skipping of exon 2 and are
differentiated by use of alternate polyadenylation signals, yielding
identical proteins of 566 amino acids. Northern blot analysis detected
5.0- and 2.5-kb transcripts in all tissues examined, with a weak 3.8-kb
transcript in heart, skeletal muscle, and pancreas.
GENE FUNCTION
Leonardi et al. (2000) verified the interaction between CIKS and
IKK-gamma by in vitro binding assays using recombinant proteins and by
coimmunoprecipitation of lysates of transfected HeLa cells or
untransfected Jurkat T-leukemic cells. IKK-alpha (CHUK; 600664) and
IKK-beta (IKBKB; 603258) also coimmunoprecipitated with CIKS. Using
truncation mutants, the authors localized the binding domain to the N
terminus of CIKS. HeLa cells transfected with increasing amounts of CIKS
showed dose-dependent activation of an Ig kappa-B luciferase reporter
plasmid, and the activation could be blocked by cotransfection with
IKK-gamma. Cotransfection of CIKS with kinase-deficient mutants of NIK
(MAP3K14; 604655), MEKK1 (MAP3K1: 600982), IKK-alpha, and IKK-beta
indicated that CIKS activates NFKB exclusively through an IKK-dependent
mechanism. Overexpressed CIKS also potently activated SAPK/JNK (MAPK8;
601158). Analysis of the binding activity of truncation mutants showed
that the C terminus of CIK is involved in SAPK/JNK activation, whereas
the N terminus is necessary and sufficient for kappa-B reporter
activation.
Using gel shift assays, Li et al. (2000) confirmed constitutive
activation of NFKB with transfection of ACT1 into human embryonic kidney
cells. They also found constitutive activation of JNK and IKK.
Disruption of the N-terminal helix-loop-helix domain of ACT1 completely
abolished the interaction between ACT1 and the IKK complex as well as
the activation of NFKB.
By mutation analysis, Pacifico et al. (2003) identified a sequence in
the 5-prime flanking region of human CIKS that was essential for basal
promoter activity in a canine kidney cell line. RT-PCR, Northern, and
Western blot analyses showed that various proinflammatory cytokines
upregulated CIKS expression in HeLa cells.
Using immunoprecipitation analysis, Qian et al. (2007) found that IL17
(603149) induced association of ACT1 with IL17RA (605461) in various
cell types. The ACT1-IL17RA interaction required the SEFIR domain of
IL17RA. Expression of Il17-dependent inflammation-related genes was
abolished in Act1-deficient mouse cells. Mice lacking Act1 had delayed
onset and lower severity of experimental allergic encephalomyelitis, as
well as limited colitis. Qian et al. (2007) concluded that ACT1 is
essential for IL17-dependent signaling in autoimmune and inflammatory
disease.
GENE STRUCTURE
Morelli et al. (2000) determined that the ACT1 gene contains 10 exons
and spans more than 50 kb. They also identified C6UAS, which overlaps
exon 2 and is transcribed in the antisense orientation from the
complementary strand of C6ORF4. C6UAS has no apparent open reading
frame, but Morelli et al. (2000) provided experimental evidence that it
has a regulatory function and can behave as an antisense RNA in the
control of C6ORF4 translation.
Pacifico et al. (2003) mapped the CIKS transcription start site and
found that the 5-prime flanking region was TATA-less, but it had
initiator, GC, and CAAT boxes.
BIOCHEMICAL FEATURES
Zhang et al. (2013) reported the structure of the IL17RB SEFIR (for
'similar expression to FGFR and IL17R;' see 136350) domain at
1.8-angstrom resolution. SEFIR displays a 5-stranded parallel beta-sheet
that is wrapped by 6 helices. Site-directed mutagenesis analysis
identified helix alphaC as being critical for interaction with ACT1
(TRAF3IP2; 607043) and IL17E (IL25; 605658) signaling. This helix is
also critical for ACT1 function and is conserved in IL17RA (605461) and
IL17RC (610925). Helix alphaB, on the other hand, is important for ACT1
homodimerization, suggesting that distinct motifs participate in binding
with different ligands. Zhang et al. (2013) proposed that the structure
helps to explain IL17R intracellular signaling and the mechanism for the
specificity of SEFIR versus the TIR (see TLR2, 603028) domain in their
respective signaling pathways.
MAPPING
Morelli et al. (2000) identified ACT1 within an EST clone that maps to
chromosome 6q21.
MOLECULAR GENETICS
- Psoriasis Susceptibility 13
Ellinghaus et al. (2010) and Huffmeier et al. (2010) independently
identified association of a coding single-nucleotide polymorphism (SNP),
dbSNP rs33980500 (607043.0001), in the TRAF3IP2 gene with psoriasis
susceptibility (PSORS13; 614070).
- Familial Candidiasis 8
In an affected brother and sister from a consanguineous Algerian family
with chronic mucocutaneous candidiasis (CANDF8; 615527), Boisson et al.
(2013) identified homozygosity for a missense mutation in the TRAF3IP2
gene (T536I; 607043.0002). Neither patient displayed psoriasis.
*FIELD* AV
.0001
PSORIASIS SUSCEPTIBILITY 13
TRAF3IP2, ASP19ASN (dbSNP rs33980500)
In a case-control genomewide association study of psoriasis
susceptibility (PSORS13; 614070), Ellinghaus et al. (2010) identified a
coding SNP, dbSNP rs33980500, in exon 2 of the TRAF3IP2 gene. A C-to-T
transition results in substitution of asn for asp at codon 19 (D19N).
This SNP was significantly associated with risk for psoriasis vulgaris
(P = 1.24 x 10(-16)) and psoriatic arthritis (P = 4.57 x 10(-12)).
In an independent case-control genomewide association study, Huffmeier
et al. (2010) found significant association of dbSNP rs33980500 with
psoriatic arthritis in a subset of cases and controls (P = 1.13 x
10(-20), OR = 1.95). Functional assays showed reducing binding of this
TRAF3IP2 variant to TRAF6 (602355), suggesting altered modulation of
immunoregulatory signals through altered TRAF interactions as a novel
and shared pathway for psoriatic arthritis and psoriasis vulgaris.
Huffmeier et al. (2010) referred to the amino acid change correlated
with this SNP as ASP10ASN.
Using fibroblasts from a healthy individual who was homozygous for the
D10N variant in TRAF3IP2, Boisson et al. (2013) observed a weak response
to stimulation with IL17A (603149) and low but detectable GRO-alpha
(155730) and IL6 (147620) induction. In addition, costimulation with
IL17A and TNFA (191160) was synergistic in this individual's cells.
Boisson et al. (2013) concluded that D10N is a hypomorphic, but not
null, allele for cellular responses to IL17A, alone or in combination
with TNFA.
.0002
CANDIDIASIS, FAMILIAL, 8 (1 family)
TRAF3IP2, THR536ILE
In an affected brother and sister from a consanguineous Algerian family
with chronic mucocutaneous candidiasis (CANDF8; 615527), Boisson et al.
(2013) identified homozygosity for a c.1607C-T transition in the
TRAF3IP2 gene, resulting in a thr536-to-ile (T536I) substitution at a
highly conserved residue in the C-terminal part of the SEFIR domain. The
mutation segregated with disease in the family and was not found in more
than 10,000 chromosomes or in the 1000 Genomes Project or dbSNP (build
135) databases. Neither of the affected sibs displayed psoriasis.
Functional analysis using patient fibroblasts and EBV-B cells
demonstrated that the T536I mutant abolishes homotypic interactions with
the SEFIR domain of IL17RA (605461), IL17RB (605458), and IL17RC
(610925), but does not affect homodimerization or SEFIR-independent ACT1
interactions with other proteins. Patient fibroblasts did not produce
IL6 (147620) in response to IL17A (603149) or IL17F (606496).
Stimulation of patient peripheral blood mononuclear cells with IL2
(147680) and/or IL17E (605658) resulted in production of IL5 (147850)
only in response to IL2, and there was no synergistic response to
costimulation. Flow cytometric analysis indicated that the patients had
higher proportions of IL17- and IL22 (605330)-producing cells but normal
levels of IFNG (147570)-producing cells, suggesting that responsiveness
to IL17 rather than production of the cytokine is critical for
protection from chronic mucocutaneous candidiasis.
*FIELD* RF
1. Boisson, B.; Wang, C.; Pedergnana, V.; Wu, L.; Cypowyj, S.; Rybojad,
M.; Belkadi, A.; Picard, C.; Abel, L.; Fieschi, C.; Puel, A.; Li,
X.; Casanova, J.-L.: An ACT1 mutation selectively abolishes interleukin-17
responses in humans with chronic mucocutaneous candidiasis. Immunity 39:
676-686, 2013.
2. Ellinghaus, E.; Ellinghaus, D.; Stuart, P. E.; Nair, R. P.; Debrus,
S.; Raelson, J. V.; Belouchi, M.; Fournier, H.; Reinhard, C.; Ding,
J.; Li, Y.; Tejasvi, T.; and 21 others: Genome-wide association
study identifies a psoriasis susceptibility locus at TRAF3IP2. Nature
Genet. 42: 991-995, 2010.
3. Huffmeier, U.; Uebe, S.; Ekici, A. B.; Bowes, J.; Giardina, E.;
Korendowych, E.; Juneblad, K.; Apel, M.; McManus, R.; Ho, P.; Bruce,
I. N.; Ryan, A. W.; and 18 others: Common variants at TRAF3IP2
are associated with susceptibility to psoriatic arthritis and psoriasis. Nature
Genet. 42: 996-999, 2010.
4. Leonardi, A.; Chariot, A.; Claudio, E.; Cunningham, K.; Siebenlist,
U.: CIKS, a connection to I-kappa-B kinase and stress-activated protein
kinase. Proc. Nat. Acad. Sci. 97: 10494-10499, 2000.
5. Li, X.; Commane, M.; Nie, H.; Hua, X.; Chatterjee-Kishore, M.;
Wald, D.; Haag, M.; Stark, G. R.: Act1, an NF-kappa-B-activating
protein. Proc. Nat. Acad. Sci. 97: 10489-10493, 2000.
6. Morelli, C.; Magnanini, C.; Mungall, A. J.; Negrini, M.; Barbanti-Brodano,
G.: Cloning and characterization of two overlapping genes in a subregion
at 6q21 involved in replicative senescence and schizophrenia. Gene 252:
217-225, 2000.
7. Pacifico, F.; Barone, C.; Mellone, S.; Di Jeso, B.; Consiglio,
E.; Formisano, S.; Vito, P.; Leonardi, A.: Promoter identification
of CIKS, a novel NF-kappa-B activating gene, and regulation of its
expression. Gene 307: 99-109, 2003.
8. Qian, Y.; Liu, C.; Hartupee, J.; Altuntas, C. Z.; Gulen, M. F.;
Jane-wit, D.; Xiao, J.; Lu, Y.; Giltiay, N.; Liu, J.; Kordula, T.;
Zhang, Q.-W.; Vallance, B.; Swaidani, S.; Aronica, M.; Tuohy, V. K.;
Hamilton, T.; Li, X.: The adaptor Act1 is required for interleukin
17-dependent signaling associated with autoimmune and inflammatory
disease. Nature Immun. 8: 247-256, 2007.
9. Zhang, B.; Liu, C.; Qian, W.; Han, Y.; Li, X.; Deng, J.: Crystal
structure of IL-17 receptor B SEFIR domain. J. Immun. 190: 2320-2326,
2013.
*FIELD* CN
Marla J. F. O'Neill - updated: 11/14/2013
Ada Hamosh - updated: 6/24/2011
Paul J. Converse - updated: 11/12/2007
*FIELD* CD
Patricia A. Hartz: 6/18/2002
*FIELD* ED
alopez: 11/15/2013
mcolton: 11/14/2013
alopez: 6/30/2011
terry: 6/24/2011
alopez: 12/19/2007
mgross: 11/12/2007
alopez: 8/7/2007
mgross: 6/19/2002
mgross: 6/18/2002
MIM
614070
*RECORD*
*FIELD* NO
614070
*FIELD* TI
#614070 PSORIASIS SUSCEPTIBILITY 13; PSORS13
*FIELD* TX
A number sign (#) is used with this entry because psoriasis
read moresusceptibility-13 is associated with variation in the TRAF3IP2 gene on
chromosome 6q21 (607043).
For phenotypic information on psoriasis and general information on other
psoriasis susceptibility loci, see PSORS1 (177900).
MAPPING
Ellinghaus et al. (2010) performed a genomewide association analysis of
over 2 million single-nucleotide polymorphisms (SNPs) in 472 psoriasis
vulgaris cases and 1,146 controls from Germany, with follow-up of the
147 most significant SNPs in 2,746 psoriasis vulgaris cases and 4,140
controls from 3 independent replication panels. Ellinghaus et al. (2010)
identified an association at TRAF3IP2 on 6q21 and genotyped 2 SNPs at
this locus in 2 additional replication panels (the combined discovery
and replication panels consisted of 6,487 cases and 8,037 controls;
combined P = 2.36 x 10(-10) for dbSNP rs13210247 and combined P = 1.24 x
10(-16) for dbSNP rs33980500). About 15% of psoriasis cases develop
psoriatic arthritis. A stratified analysis of their datasets including
only psoriatic arthritis cases (1,922 cases compared to 8,037 controls,
P = 4.57 x 10(-12) for dbSNP rs33980500) suggested that TRAF3IP2
represents a shared susceptibility for psoriasis vulgaris and psoriatic
arthritis. TRAF3IP2 encodes a protein involved in IL17 (603149)
signaling and interacts with members of the Rel/NF-kappa-B transcription
factor family (see 164014). Ellinghaus et al. (2010) tested for the
presence of statistical interaction between dbSNP rs33980500 (asp19 to
asn) genotypes and HLA-Cw6 (see 142840.0001) carriership in a subset of
993 cases and 2,277 controls for whom HLA-Cw6 status was available, and
found no statistical support for interaction (P = 0.77).
Huffmeier et al. (2010) conducted a genomewide association study in 609
German individuals with psoriatic arthritis and 990 controls with
replication in 6 European cohorts including a total of 5,488
individuals. Huffmeier et al. (2010) replicated psoriatic arthritis
associations at HLA-C (177900) and IL12B (612599) and identified a new
association at TRAF3IP2 (dbSNP rs13190932, P = 8.56 x 10(-17)). TRAF3IP2
was also associated with psoriasis vulgaris in a German cohort including
2,040 individuals (dbSNP rs13190932, P = 1.95 x 10(-3)). Sequencing of
the exons of TRAF3IP2 identified a coding variant, dbSNP rs33980500,
(asp10 to asn) as the most significantly associated SNP (P = 1.13 x
10(-20), odds ratio = 1.95). Functional assays showed reduced binding of
this TRAF3IP2 variant to TRAF6 (602355), suggesting altered modulation
of immunoregulatory signals through altered TRAF interactions as a novel
and shared pathway for psoriatic arthritis and psoriasis vulgaris.
*FIELD* RF
1. Ellinghaus, E.; Ellinghaus, D.; Stuart, P. E.; Nair, R. P.; Debrus,
S.; Raelson, J. V.; Belouchi, M.; Fournier, H.; Reinhard, C.; Ding,
J.; Li, Y.; Tejasvi, T.; and 21 others: Genome-wide association
study identifies a psoriasis susceptibility locus at TRAF3IP2. Nature
Genet. 42: 991-995, 2010.
2. Huffmeier, U.; Uebe, S.; Ekici, A. B.; Bowes, J.; Giardina, E.;
Korendowych, E.; Juneblad, K.; Apel, M.; McManus, R.; Ho, P.; Bruce,
I. N.; Ryan, A. W.; and 18 others: Common variants at TRAF3IP2
are associated with susceptibility to psoriatic arthritis and psoriasis. Nature
Genet. 42: 996-999, 2010.
*FIELD* CD
Ada Hamosh: 6/30/2011
*FIELD* ED
alopez: 06/30/2011
*RECORD*
*FIELD* NO
614070
*FIELD* TI
#614070 PSORIASIS SUSCEPTIBILITY 13; PSORS13
*FIELD* TX
A number sign (#) is used with this entry because psoriasis
read moresusceptibility-13 is associated with variation in the TRAF3IP2 gene on
chromosome 6q21 (607043).
For phenotypic information on psoriasis and general information on other
psoriasis susceptibility loci, see PSORS1 (177900).
MAPPING
Ellinghaus et al. (2010) performed a genomewide association analysis of
over 2 million single-nucleotide polymorphisms (SNPs) in 472 psoriasis
vulgaris cases and 1,146 controls from Germany, with follow-up of the
147 most significant SNPs in 2,746 psoriasis vulgaris cases and 4,140
controls from 3 independent replication panels. Ellinghaus et al. (2010)
identified an association at TRAF3IP2 on 6q21 and genotyped 2 SNPs at
this locus in 2 additional replication panels (the combined discovery
and replication panels consisted of 6,487 cases and 8,037 controls;
combined P = 2.36 x 10(-10) for dbSNP rs13210247 and combined P = 1.24 x
10(-16) for dbSNP rs33980500). About 15% of psoriasis cases develop
psoriatic arthritis. A stratified analysis of their datasets including
only psoriatic arthritis cases (1,922 cases compared to 8,037 controls,
P = 4.57 x 10(-12) for dbSNP rs33980500) suggested that TRAF3IP2
represents a shared susceptibility for psoriasis vulgaris and psoriatic
arthritis. TRAF3IP2 encodes a protein involved in IL17 (603149)
signaling and interacts with members of the Rel/NF-kappa-B transcription
factor family (see 164014). Ellinghaus et al. (2010) tested for the
presence of statistical interaction between dbSNP rs33980500 (asp19 to
asn) genotypes and HLA-Cw6 (see 142840.0001) carriership in a subset of
993 cases and 2,277 controls for whom HLA-Cw6 status was available, and
found no statistical support for interaction (P = 0.77).
Huffmeier et al. (2010) conducted a genomewide association study in 609
German individuals with psoriatic arthritis and 990 controls with
replication in 6 European cohorts including a total of 5,488
individuals. Huffmeier et al. (2010) replicated psoriatic arthritis
associations at HLA-C (177900) and IL12B (612599) and identified a new
association at TRAF3IP2 (dbSNP rs13190932, P = 8.56 x 10(-17)). TRAF3IP2
was also associated with psoriasis vulgaris in a German cohort including
2,040 individuals (dbSNP rs13190932, P = 1.95 x 10(-3)). Sequencing of
the exons of TRAF3IP2 identified a coding variant, dbSNP rs33980500,
(asp10 to asn) as the most significantly associated SNP (P = 1.13 x
10(-20), odds ratio = 1.95). Functional assays showed reduced binding of
this TRAF3IP2 variant to TRAF6 (602355), suggesting altered modulation
of immunoregulatory signals through altered TRAF interactions as a novel
and shared pathway for psoriatic arthritis and psoriasis vulgaris.
*FIELD* RF
1. Ellinghaus, E.; Ellinghaus, D.; Stuart, P. E.; Nair, R. P.; Debrus,
S.; Raelson, J. V.; Belouchi, M.; Fournier, H.; Reinhard, C.; Ding,
J.; Li, Y.; Tejasvi, T.; and 21 others: Genome-wide association
study identifies a psoriasis susceptibility locus at TRAF3IP2. Nature
Genet. 42: 991-995, 2010.
2. Huffmeier, U.; Uebe, S.; Ekici, A. B.; Bowes, J.; Giardina, E.;
Korendowych, E.; Juneblad, K.; Apel, M.; McManus, R.; Ho, P.; Bruce,
I. N.; Ryan, A. W.; and 18 others: Common variants at TRAF3IP2
are associated with susceptibility to psoriatic arthritis and psoriasis. Nature
Genet. 42: 996-999, 2010.
*FIELD* CD
Ada Hamosh: 6/30/2011
*FIELD* ED
alopez: 06/30/2011