ID IRF6_HUMAN Reviewed; 467 AA. AC O14896; B4DLE2; D3DT90; F5GWX8; G0ZTL0; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 11-NOV-2015, entry version 152. DE RecName: Full=Interferon regulatory factor 6; DE Short=IRF-6; GN Name=IRF6; 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] (ISOFORM 1). RA Grossman A., Mittrucker H.W., Antonio L., Ozato K., Mak T.W.; RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ILE-274. RA Wang H., Wu W., Hua L., Li F., Chen Y., Cui Y.; RT "Homo sapiens interferon regulatory factor 6 (IRF6) gene sequence from RT Hakka population in Guangdong Province, South China."; RL Submitted (FEB-2011) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT RP ILE-274. RC TISSUE=Tongue; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; 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 [7] RP INTERACTION WITH SERPINB5, PHOSPHORYLATION, TISSUE SPECIFICITY, AND RP SUBCELLULAR LOCATION. RX PubMed=16049006; DOI=10.1074/jbc.M503523200; RA Bailey C.M., Khalkhali-Ellis Z., Kondo S., Margaryan N.V., RA Seftor R.E.B., Wheaton W.W., Amir S., Pins M.R., Schutte B.C., RA Hendrix M.J.C.; RT "Mammary serine protease inhibitor (Maspin) binds directly to RT interferon regulatory factor 6: identification of a novel serpin RT partnership."; RL J. Biol. Chem. 280:34210-34217(2005). RN [8] RP SUBCELLULAR LOCATION, UBIQUITINATION, AND PHOSPHORYLATION. RX PubMed=18212048; DOI=10.1128/MCB.01866-07; RA Bailey C.M., Abbott D.E., Margaryan N.V., Khalkhali-Ellis Z., RA Hendrix M.J.C.; RT "Interferon regulatory factor 6 promotes cell cycle arrest and is RT regulated by the proteasome in a cell cycle-dependent manner."; RL Mol. Cell. Biol. 28:2235-2243(2008). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [10] RP VARIANTS VWS1 VAL-2; ALA-18; MET-18; ALA-39; GLY-61; ARG-70; SER-76; RP HIS-88; GLY-90; HIS-98; GLN-250; ARG-273; 290-PHE--ASP-296 DELINS LEU; RP PRO-294; ILE-297; GLU-320; MET-321; GLU-325; PRO-345; PHE-347; RP SER-369; TRP-374 AND GLU-388, VARIANTS PPS GLY-60; THR-66; LYS-82; RP CYS-84; HIS-84; GLU-89 AND ASN-430, AND VARIANT ILE-274. RX PubMed=12219090; DOI=10.1038/ng985; RA Kondo S., Schutte B.C., Richardson R.J., Bjork B.C., Knight A.S., RA Watanabe Y., Howard E., de Lima R.L.L., Daack-Hirsch S., Sander A., RA McDonald-McGinn D.M., Zackai E.H., Lammer E.J., Aylsworth A.S., RA Ardinger H.H., Lidral A.C., Pober B.R., Moreno L., Arcos-Burgos M., RA Valencia C., Houdayer C., Bahuau M., Moretti-Ferreira D., RA Richieri-Costa A., Dixon M.J., Murray J.C.; RT "Mutations in IRF6 cause Van der Woude and popliteal pterygium RT syndromes."; RL Nat. Genet. 32:285-289(2002). RN [11] RP VARIANTS VWS1 VAL-2; CYS-6 AND TRP-400. RX PubMed=12920575; DOI=10.1007/s00439-003-0989-2; RA Wang X., Liu J., Zhang H., Xiao M., Li J., Yang C., Lin X., Wu Z., RA Hu L., Kong X.; RT "Novel mutations in the IRF6 gene for Van der Woude syndrome."; RL Hum. Genet. 113:382-386(2003). RN [12] RP VARIANTS VWS1 VAL-16; ILE-64; ALA-100 AND PRO-251, AND VARIANT RP VWS1/PPS PRO-22. RX PubMed=14640121; RA Ghassibe M., Revencu N., Bayet B., Gillerot Y., Vanwijck R., RA Verellen-Dumoulin C., Vikkula M.; RT "Gene symbol IRF6. Disease: Van der Woude syndrome and popliteal RT pterygium."; RL Hum. Genet. 113:558-558(2003). RN [13] RP VARIANTS VWS1 GLN-45 AND SER-396. RX PubMed=14618417; DOI=10.1007/s10038-003-0089-0; RA Kayano S., Kure S., Suzuki Y., Kanno K., Aoki Y., Kondo S., RA Schutte B.C., Murray J.C., Yamada A., Matsubara Y.; RT "Novel IRF6 mutations in Japanese patients with Van der Woude RT syndrome: two missense mutations (R45Q and P396S) and a 17-kb RT deletion."; RL J. Hum. Genet. 48:622-628(2003). RN [14] RP VARIANT VWS1 GLY-84. RX PubMed=15300989; RA Item C.B., Turhani D., Thurnher D., Sinko K., Yerit K., Galev K., RA Wittwer G., Lanre Adeyemo W., Klemens F., Ewers R., Watzinger F.; RT "Gene symbol: IRF6. Disease: Van der Woude syndrome."; RL Hum. Genet. 115:175-175(2004). RN [15] RP ASSOCIATION OF VARIANT ILE-274 WITH OFC6. RX PubMed=15317890; DOI=10.1056/NEJMoa032909; RA Zucchero T.M., Cooper M.E., Maher B.S., Daack-Hirsch S., RA Nepomuceno B., Ribeiro L., Caprau D., Christensen K., Suzuki Y., RA Machida J., Natsume N., Yoshiura K., Vieira A.R., Orioli I.M., RA Castilla E.E., Moreno L., Arcos-Burgos M., Lidral A.C., Field L.L., RA Liu Y.-E., Ray A., Goldstein T.H., Schultz R.E., Shi M., Johnson M.K., RA Kondo S., Schutte B.C., Marazita M.L., Murray J.C.; RT "Interferon regulatory factor 6 (IRF6) gene variants and the risk of RT isolated cleft lip or palate."; RL N. Engl. J. Med. 351:769-780(2004). RN [16] RP VARIANT VWS1 VAL-349. RX PubMed=17122170; DOI=10.1177/154405910608501215; RA Matsuzawa N., Shimozato K., Natsume N., Niikawa N., Yoshiura K.; RT "A novel missense mutation in Van der Woude syndrome: usefulness of RT fingernail DNA for genetic analysis."; RL J. Dent. Res. 85:1143-1146(2006). RN [17] RP VARIANT VWS1 ILE-339. RX PubMed=18478600; DOI=10.1002/ajmg.a.32257; RA de Medeiros F., Hansen L., Mawlad E., Eiberg H., Asklund C., RA Tommerup N., Jakobsen L.P.; RT "A novel mutation in IRF6 resulting in VWS-PPS spectrum disorder with RT renal aplasia."; RL Am. J. Med. Genet. A 146:1605-1608(2008). RN [18] RP CHARACTERIZATION OF VARIANTS VWS1/PPS ALA-18; MET-18; PRO-22; GLY-60; RP ARG-70; SER-76; CYS-84; GLY-84; HIS-84; GLU-89 AND HIS-98. RX PubMed=19036739; DOI=10.1093/hmg/ddn381; RA Little H.J., Rorick N.K., Su L.-I., Baldock C., Malhotra S., RA Jowitt T., Gakhar L., Subramanian R., Schutte B.C., Dixon M.J., RA Shore P.; RT "Missense mutations that cause Van der Woude syndrome and popliteal RT pterygium syndrome affect the DNA-binding and transcriptional RT activation functions of IRF6."; RL Hum. Mol. Genet. 18:535-545(2009). RN [19] RP VARIANTS PPS LEU-84 AND LEU-424, AND CHARACTERIZATION OF VARIANT PPS RP LEU-424. RX PubMed=20803643; DOI=10.1002/ajmg.a.33338; RA Matsuzawa N., Kondo S., Shimozato K., Nagao T., Nakano M., Tsuda M., RA Hirano A., Niikawa N., Yoshiura K.; RT "Two missense mutations of the IRF6 gene in two Japanese families with RT popliteal pterygium syndrome."; RL Am. J. Med. Genet. A 152:2262-2267(2010). RN [20] RP VARIANT OFC6 SER-369. RX PubMed=21082654; DOI=10.1002/ajmg.a.33053; RA Rutledge K.D., Barger C., Grant J.H., Robin N.H.; RT "IRF6 mutations in mixed isolated familial clefting."; RL Am. J. Med. Genet. A 152:3107-3109(2010). CC -!- FUNCTION: Probable DNA-binding transcriptional activator. Key CC determinant of the keratinocyte proliferation-differentiation CC switch involved in appropriate epidermal development (By CC similarity). Plays a role in regulating mammary epithelial cell CC proliferation (By similarity). May regulate WDR65 transcription CC (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Interacts with SERPINB5. {ECO:0000269|PubMed:16049006}. CC -!- INTERACTION: CC Q02556:IRF8; NbExp=3; IntAct=EBI-6115643, EBI-2866563; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. Cytoplasm CC {ECO:0000269|PubMed:16049006, ECO:0000269|PubMed:18212048}. CC Note=Translocates to nucleus in response to an activating signal. CC {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O14896-1; Sequence=Displayed; CC Name=2; CC IsoId=O14896-2; Sequence=VSP_046435; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed in normal mammary epithelial cells. CC Expression is reduced or absent in breast carcinomas. CC {ECO:0000269|PubMed:16049006}. CC -!- PTM: Phosphorylated. Phosphorylation status depends on the cell CC cycle and is a signal for ubiquitination and proteasome-mediated CC degradation. {ECO:0000269|PubMed:16049006, CC ECO:0000269|PubMed:18212048}. CC -!- DISEASE: Van der Woude syndrome 1 (VWS1) [MIM:119300]: An CC autosomal dominant developmental disorder characterized by lower CC lip pits, cleft lip and/or cleft palate. CC {ECO:0000269|PubMed:12219090, ECO:0000269|PubMed:12920575, CC ECO:0000269|PubMed:14618417, ECO:0000269|PubMed:14640121, CC ECO:0000269|PubMed:15300989, ECO:0000269|PubMed:17122170, CC ECO:0000269|PubMed:18478600}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Popliteal pterygium syndrome (PPS) [MIM:119500]: An CC autosomal dominant disorder characterized by oro-facial, skin and CC genital anomalies. Expressivity is variable. Clinical features CC include cleft lip/palate, lower lip cysts, syngnathia, congenital CC ankyloblepharon filiforme in some cases, bifid scrotum, CC hypoplastic scrotum, hypoplastic uterus, talipes equinovarus. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- DISEASE: Non-syndromic orofacial cleft 6 (OFC6) [MIM:608864]: A CC birth defect consisting of cleft lips with or without cleft CC palate. Cleft lips are associated with cleft palate in two-third CC of cases. A cleft lip can occur on one or both sides and range in CC severity from a simple notch in the upper lip to a complete CC opening in the lip extending into the floor of the nostril and CC involving the upper gum. {ECO:0000269|PubMed:15317890, CC ECO:0000269|PubMed:21082654}. Note=Disease susceptibility is CC associated with variations affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the IRF family. {ECO:0000255|PROSITE- CC ProRule:PRU00840}. CC -!- SIMILARITY: Contains 1 IRF tryptophan pentad repeat DNA-binding CC domain. {ECO:0000255|PROSITE-ProRule:PRU00840}. 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; AF027292; AAB84111.1; -; mRNA. DR EMBL; JF346417; AEL89176.1; -; Genomic_DNA. DR EMBL; AK296960; BAG59504.1; -; mRNA. DR EMBL; AL022398; CAA18545.1; -; Genomic_DNA. DR EMBL; CH471100; EAW93438.1; -; Genomic_DNA. DR EMBL; CH471100; EAW93439.1; -; Genomic_DNA. DR EMBL; BC014852; AAH14852.1; -; mRNA. DR CCDS; CCDS1492.1; -. [O14896-1] DR CCDS; CCDS55681.1; -. [O14896-2] DR RefSeq; NP_001193625.1; NM_001206696.1. [O14896-2] DR RefSeq; NP_006138.1; NM_006147.3. [O14896-1] DR UniGene; Hs.591415; -. DR ProteinModelPortal; O14896; -. DR SMR; O14896; 12-112, 214-445. DR BioGrid; 109872; 8. DR IntAct; O14896; 3. DR STRING; 9606.ENSP00000355988; -. DR PhosphoSite; O14896; -. DR BioMuta; IRF6; -. DR MaxQB; O14896; -. DR PaxDb; O14896; -. DR PeptideAtlas; O14896; -. DR PRIDE; O14896; -. DR Ensembl; ENST00000367021; ENSP00000355988; ENSG00000117595. [O14896-1] DR Ensembl; ENST00000542854; ENSP00000440532; ENSG00000117595. [O14896-2] DR GeneID; 3664; -. DR KEGG; hsa:3664; -. DR UCSC; uc001hhq.2; human. [O14896-1] DR CTD; 3664; -. DR GeneCards; IRF6; -. DR GeneReviews; IRF6; -. DR HGNC; HGNC:6121; IRF6. DR MIM; 119300; phenotype. DR MIM; 119500; phenotype. DR MIM; 607199; gene. DR MIM; 608864; phenotype. DR neXtProt; NX_O14896; -. DR Orphanet; 1300; Autosomal dominant popliteal pterygium syndrome. DR Orphanet; 1991; Cleft lip with or without cleft palate. DR Orphanet; 2227; Hypodontia. DR Orphanet; 99798; Oligodontia. DR Orphanet; 888; Van der Woude syndrome. DR PharmGKB; PA29920; -. DR eggNOG; ENOG410IFCV; Eukaryota. DR eggNOG; ENOG410XRXT; LUCA. DR GeneTree; ENSGT00760000119093; -. DR HOGENOM; HOG000037433; -. DR HOVERGEN; HBG105715; -. DR InParanoid; O14896; -. DR KO; K10154; -. DR OMA; WQPMQPA; -. DR OrthoDB; EOG7CCBR1; -. DR PhylomeDB; O14896; -. DR TreeFam; TF328512; -. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR Reactome; R-HSA-909733; Interferon alpha/beta signaling. DR ChiTaRS; IRF6; human. DR GeneWiki; IRF6; -. DR GenomeRNAi; 3664; -. DR NextBio; 14343; -. DR PRO; PR:O14896; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; O14896; -. DR CleanEx; HS_IRF6; -. DR ExpressionAtlas; O14896; baseline and differential. DR Genevisible; O14896; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB. DR GO; GO:0000975; F:regulatory region DNA binding; IEA:InterPro. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; ISS:UniProtKB. DR GO; GO:0007050; P:cell cycle arrest; IDA:UniProtKB. DR GO; GO:0048468; P:cell development; IEA:Ensembl. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome. DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome. DR GO; GO:0030216; P:keratinocyte differentiation; IEA:Ensembl. DR GO; GO:0043616; P:keratinocyte proliferation; IEA:Ensembl. DR GO; GO:0060644; P:mammary gland epithelial cell differentiation; ISS:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell proliferation; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0060337; P:type I interferon signaling pathway; TAS:Reactome. DR Gene3D; 1.10.10.10; -; 1. DR Gene3D; 2.60.200.10; -; 1. DR InterPro; IPR019817; Interferon_reg_fac_CS. DR InterPro; IPR001346; Interferon_reg_fact_DNA-bd_dom. DR InterPro; IPR019471; Interferon_reg_factor-3. DR InterPro; IPR017855; SMAD_dom-like. DR InterPro; IPR008984; SMAD_FHA_domain. DR InterPro; IPR011991; WHTH_DNA-bd_dom. DR Pfam; PF00605; IRF; 1. DR Pfam; PF10401; IRF-3; 1. DR PRINTS; PR00267; INTFRNREGFCT. DR SMART; SM00348; IRF; 1. DR SUPFAM; SSF49879; SSF49879; 1. DR PROSITE; PS00601; IRF_1; 1. DR PROSITE; PS51507; IRF_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; Cytoplasm; Differentiation; KW Disease mutation; DNA-binding; Nucleus; Polymorphism; KW Reference proteome; Transcription; Transcription regulation; KW Ubl conjugation. FT CHAIN 1 467 Interferon regulatory factor 6. FT /FTId=PRO_0000154560. FT DNA_BIND 7 115 IRF tryptophan pentad repeat. FT {ECO:0000255|PROSITE-ProRule:PRU00840}. FT VAR_SEQ 1 95 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_046435. FT VARIANT 2 2 A -> V (in VWS1; dbSNP:rs28942093). FT {ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:12920575}. FT /FTId=VAR_014961. FT VARIANT 6 6 R -> C (in VWS1; dbSNP:rs28942094). FT {ECO:0000269|PubMed:12920575}. FT /FTId=VAR_030046. FT VARIANT 16 16 A -> V (in VWS1). FT {ECO:0000269|PubMed:14640121}. FT /FTId=VAR_030047. FT VARIANT 18 18 V -> A (in VWS1; abrogates DNA binding). FT {ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739}. FT /FTId=VAR_014962. FT VARIANT 18 18 V -> M (in VWS1; abrogates DNA binding). FT {ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739}. FT /FTId=VAR_014963. FT VARIANT 22 22 L -> P (in VWS1 and PPS; abrogates DNA FT binding). {ECO:0000269|PubMed:14640121, FT ECO:0000269|PubMed:19036739}. FT /FTId=VAR_030048. FT VARIANT 39 39 P -> A (in VWS1). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014964. FT VARIANT 45 45 R -> Q (in VWS1; dbSNP:rs121434229). FT {ECO:0000269|PubMed:14618417}. FT /FTId=VAR_030049. FT VARIANT 60 60 W -> G (in PPS; abrogates DNA binding). FT {ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739}. FT /FTId=VAR_014965. FT VARIANT 61 61 A -> G (in VWS1). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014966. FT VARIANT 64 64 T -> I (in VWS1). FT {ECO:0000269|PubMed:14640121}. FT /FTId=VAR_030050. FT VARIANT 66 66 K -> T (in PPS). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014967. FT VARIANT 70 70 G -> R (in VWS1; does not affect DNA FT binding). {ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739}. FT /FTId=VAR_014968. FT VARIANT 76 76 P -> S (in VWS1; abrogates DNA binding). FT {ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739}. FT /FTId=VAR_014969. FT VARIANT 82 82 Q -> K (in PPS). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014970. FT VARIANT 84 84 R -> C (in PPS; abrogates DNA binding). FT {ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739}. FT /FTId=VAR_014971. FT VARIANT 84 84 R -> G (in VWS1; abrogates DNA binding). FT {ECO:0000269|PubMed:15300989, FT ECO:0000269|PubMed:19036739}. FT /FTId=VAR_030051. FT VARIANT 84 84 R -> H (in PPS; abrogates DNA binding). FT {ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739}. FT /FTId=VAR_014972. FT VARIANT 84 84 R -> L (in PPS). FT {ECO:0000269|PubMed:20803643}. FT /FTId=VAR_064475. FT VARIANT 88 88 N -> H (in VWS1). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014973. FT VARIANT 89 89 K -> E (in PPS; abrogates DNA binding). FT {ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739}. FT /FTId=VAR_014974. FT VARIANT 90 90 S -> G (in VWS1). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014975. FT VARIANT 98 98 D -> H (in VWS1; abrogates DNA binding). FT {ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739}. FT /FTId=VAR_014976. FT VARIANT 100 100 T -> A (in VWS1). FT {ECO:0000269|PubMed:14640121}. FT /FTId=VAR_030052. FT VARIANT 250 250 R -> Q (in VWS1). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014977. FT VARIANT 251 251 L -> P (in VWS1). FT {ECO:0000269|PubMed:14640121}. FT /FTId=VAR_030053. FT VARIANT 273 273 Q -> R (in VWS1). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014978. FT VARIANT 274 274 V -> I (common polymorphism; 3% in FT European-descended and 22% in Asian FT populations; responsible for 12% of the FT genetic contribution to cleft lip or FT palate; tripled the risk of recurrence in FT families that already had 1 affected FT child; dbSNP:rs2235371). FT {ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:14702039, FT ECO:0000269|Ref.2}. FT /FTId=VAR_014979. FT VARIANT 290 296 FTSKLLD -> L (in VWS1). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014980. FT VARIANT 294 294 L -> P (in VWS1). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014981. FT VARIANT 297 297 V -> I (in VWS1). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014982. FT VARIANT 320 320 K -> E (in VWS1). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014983. FT VARIANT 321 321 V -> M (in VWS1). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014984. FT VARIANT 325 325 G -> E (in VWS1). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014985. FT VARIANT 339 339 R -> I (in VWS1). FT {ECO:0000269|PubMed:18478600}. FT /FTId=VAR_059080. FT VARIANT 345 345 L -> P (in VWS1). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014986. FT VARIANT 347 347 C -> F (in VWS1). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014987. FT VARIANT 349 349 E -> V (in VWS1). FT {ECO:0000269|PubMed:17122170}. FT /FTId=VAR_030054. FT VARIANT 369 369 F -> S (in VWS1 and OFC6). FT {ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:21082654}. FT /FTId=VAR_014988. FT VARIANT 374 374 C -> W (in VWS1). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014989. FT VARIANT 388 388 K -> E (in VWS1). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014990. FT VARIANT 396 396 P -> S (in VWS1). FT {ECO:0000269|PubMed:14618417}. FT /FTId=VAR_030055. FT VARIANT 400 400 R -> W (in VWS1; dbSNP:rs28942095). FT {ECO:0000269|PubMed:12920575}. FT /FTId=VAR_030056. FT VARIANT 424 424 S -> L (in PPS; significant decrease of FT transcriptional activity). FT {ECO:0000269|PubMed:20803643}. FT /FTId=VAR_064476. FT VARIANT 430 430 D -> N (in PPS). FT {ECO:0000269|PubMed:12219090}. FT /FTId=VAR_014991. SQ SEQUENCE 467 AA; 53130 MW; 7E28F5E0F5BA4053 CRC64; MALHPRRVRL KPWLVAQVDS GLYPGLIWLH RDSKRFQIPW KHATRHSPQQ EEENTIFKAW AVETGKYQEG VDDPDPAKWK AQLRCALNKS REFNLMYDGT KEVPMNPVKI YQVCDIPQPQ GSIINPGSTG SAPWDEKDND VDEEDEEDEL DQSQHHVPIQ DTFPFLNING SPMAPASVGN CSVGNCSPEA VWPKTEPLEM EVPQAPIQPF YSSPELWISS LPMTDLDIKF QYRGKEYGQT MTVSNPQGCR LFYGDLGPMP DQEELFGPVS LEQVKFPGPE HITNEKQKLF TSKLLDVMDR GLILEVSGHA IYAIRLCQCK VYWSGPCAPS LVAPNLIERQ KKVKLFCLET FLSDLIAHQK GQIEKQPPFE IYLCFGEEWP DGKPLERKLI LVQVIPVVAR MIYEMFSGDF TRSFDSGSVR LQISTPDIKD NIVAQLKQLY RILQTQESWQ PMQPTPSMQL PPALPPQ //