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 27-MAR-2024, entry version 209. 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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 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., 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 [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., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., 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., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., 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., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., 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., 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 [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 project: RT 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., Seftor R.E.B., RA Wheaton W.W., Amir S., Pins M.R., Schutte B.C., Hendrix M.J.C.; RT "Mammary serine protease inhibitor (Maspin) binds directly to interferon RT regulatory factor 6: identification of a novel serpin 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 regulated RT 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., Buerckstuemmer T., RA 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; SER-369; RP TRP-374 AND GLU-388, VARIANTS PPS GLY-60; THR-66; LYS-82; CYS-84; HIS-84; RP 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 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., Hu L., RA 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 VWS1/PPS RP 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., Schutte B.C., RA Murray J.C., Yamada A., Matsubara Y.; RT "Novel IRF6 mutations in Japanese patients with Van der Woude syndrome: two RT missense mutations (R45Q and P396S) and a 17-kb 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., Nepomuceno B., RA Ribeiro L., Caprau D., Christensen K., Suzuki Y., Machida J., Natsume N., RA Yoshiura K., Vieira A.R., Orioli I.M., Castilla E.E., Moreno L., RA Arcos-Burgos M., Lidral A.C., Field L.L., Liu Y.-E., Ray A., RA Goldstein T.H., Schultz R.E., Shi M., Johnson M.K., Kondo S., Schutte B.C., RA 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., Tommerup N., RA Jakobsen L.P.; RT "A novel mutation in IRF6 resulting in VWS-PPS spectrum disorder with renal RT 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., Jowitt T., RA Gakhar L., Subramanian R., Schutte B.C., Dixon M.J., Shore P.; RT "Missense mutations that cause Van der Woude syndrome and popliteal RT pterygium syndrome affect the DNA-binding and transcriptional activation RT 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). RN [21] RP VARIANT PPS PRO-439. RX PubMed=25691407; DOI=10.1002/ajmg.a.36896; RA Leslie E.J., O'Sullivan J., Cunningham M.L., Singh A., Goudy S.L., RA Ababneh F., Alsubaie L., Ch'ng G.S., van der Laar I.M., Hoogeboom A.J., RA Dunnwald M., Kapoor S., Jiramongkolchai P., Standley J., Manak J.R., RA Murray J.C., Dixon M.J.; RT "Expanding the genetic and phenotypic spectrum of popliteal pterygium RT disorders."; RL Am. J. Med. Genet. A 167A:545-552(2015). CC -!- FUNCTION: Probable DNA-binding transcriptional activator. Key CC determinant of the keratinocyte proliferation-differentiation switch CC involved in appropriate epidermal development (By similarity). Plays a CC role in regulating mammary epithelial cell proliferation (By CC similarity). May regulate WDR65 transcription (By similarity). CC {ECO:0000250}. CC -!- SUBUNIT: Interacts with SERPINB5. {ECO:0000269|PubMed:16049006}. CC -!- INTERACTION: CC O14896; 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 -!- 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 cycle CC and is a signal for ubiquitination and proteasome-mediated degradation. CC {ECO:0000269|PubMed:16049006, ECO:0000269|PubMed:18212048}. CC -!- DISEASE: Van der Woude syndrome 1 (VWS1) [MIM:119300]: An autosomal CC dominant developmental disorder characterized by lower lip pits, cleft CC lip and/or cleft palate. {ECO:0000269|PubMed:12219090, CC ECO:0000269|PubMed:12920575, ECO:0000269|PubMed:14618417, CC ECO:0000269|PubMed:14640121, ECO:0000269|PubMed:15300989, CC ECO:0000269|PubMed:17122170, ECO:0000269|PubMed:18478600, CC ECO:0000269|PubMed:19036739}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Popliteal pterygium syndrome (PPS) [MIM:119500]: An autosomal CC dominant disorder characterized by oro-facial, skin and genital CC anomalies. Expressivity is variable. Clinical features include cleft CC lip/palate, lower lip cysts, syngnathia, congenital ankyloblepharon CC filiforme in some cases, bifid scrotum, hypoplastic scrotum, CC hypoplastic uterus, talipes equinovarus. {ECO:0000269|PubMed:12219090, CC ECO:0000269|PubMed:14640121, ECO:0000269|PubMed:19036739, CC ECO:0000269|PubMed:20803643, ECO:0000269|PubMed:25691407}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Non-syndromic orofacial cleft 6 (OFC6) [MIM:608864]: A birth CC defect consisting of cleft lips with or without cleft palate. Cleft CC lips are associated with cleft palate in two-third of cases. A cleft CC lip can occur on one or both sides and range in severity from a simple CC notch in the upper lip to a complete opening in the lip extending into CC the floor of the nostril and involving the upper gum. CC {ECO:0000269|PubMed:15317890, ECO:0000269|PubMed:21082654}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. CC -!- SIMILARITY: Belongs to the IRF family. {ECO:0000255|PROSITE- CC 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; -; NOT_ANNOTATED_CDS; 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 AlphaFoldDB; O14896; -. DR SMR; O14896; -. DR BioGRID; 109872; 16. DR IntAct; O14896; 14. DR MINT; O14896; -. DR STRING; 9606.ENSP00000355988; -. DR iPTMnet; O14896; -. DR PhosphoSitePlus; O14896; -. DR BioMuta; IRF6; -. DR EPD; O14896; -. DR jPOST; O14896; -. DR MassIVE; O14896; -. DR MaxQB; O14896; -. DR PaxDb; 9606-ENSP00000355988; -. DR PeptideAtlas; O14896; -. DR ProteomicsDB; 24251; -. DR ProteomicsDB; 48286; -. [O14896-1] DR Pumba; O14896; -. DR TopDownProteomics; O14896-1; -. [O14896-1] DR Antibodypedia; 20702; 498 antibodies from 40 providers. DR DNASU; 3664; -. DR Ensembl; ENST00000367021.8; ENSP00000355988.3; ENSG00000117595.13. [O14896-1] DR Ensembl; ENST00000542854.5; ENSP00000440532.1; ENSG00000117595.13. [O14896-2] DR GeneID; 3664; -. DR KEGG; hsa:3664; -. DR MANE-Select; ENST00000367021.8; ENSP00000355988.3; NM_006147.4; NP_006138.1. DR UCSC; uc001hhq.3; human. [O14896-1] DR AGR; HGNC:6121; -. DR CTD; 3664; -. DR DisGeNET; 3664; -. DR GeneCards; IRF6; -. DR GeneReviews; IRF6; -. DR HGNC; HGNC:6121; IRF6. DR HPA; ENSG00000117595; Tissue enhanced (esophagus, skin). DR MalaCards; IRF6; -. DR MIM; 119300; phenotype. DR MIM; 119500; phenotype. DR MIM; 607199; gene. DR MIM; 608864; phenotype. DR neXtProt; NX_O14896; -. DR OpenTargets; ENSG00000117595; -. DR Orphanet; 1300; Autosomal dominant popliteal pterygium syndrome. DR Orphanet; 141291; Cleft lip and alveolus. DR Orphanet; 199306; Cleft lip/palate. DR Orphanet; 199302; Isolated cleft lip. DR Orphanet; 2227; NON RARE IN EUROPE: Hypodontia. DR Orphanet; 99798; Oligodontia. DR Orphanet; 888; Van der Woude syndrome. DR PharmGKB; PA29920; -. DR VEuPathDB; HostDB:ENSG00000117595; -. DR eggNOG; ENOG502QRNT; Eukaryota. DR GeneTree; ENSGT00940000157451; -. DR InParanoid; O14896; -. DR OMA; NEAWPKE; -. DR OrthoDB; 3740806at2759; -. DR PhylomeDB; O14896; -. DR TreeFam; TF328512; -. DR PathwayCommons; O14896; -. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR Reactome; R-HSA-909733; Interferon alpha/beta signaling. DR SignaLink; O14896; -. DR BioGRID-ORCS; 3664; 6 hits in 1175 CRISPR screens. DR ChiTaRS; IRF6; human. DR GeneWiki; IRF6; -. DR GenomeRNAi; 3664; -. DR Pharos; O14896; Tbio. DR PRO; PR:O14896; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; O14896; Protein. DR Bgee; ENSG00000117595; Expressed in secondary oocyte and 151 other cell types or tissues. DR ExpressionAtlas; O14896; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl. DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0048468; P:cell development; IEA:Ensembl. DR GO; GO:1904888; P:cranial skeletal system development; IEA:Ensembl. DR GO; GO:0002376; P:immune system process; IBA:GO_Central. DR GO; GO:0030216; P:keratinocyte differentiation; IEA:Ensembl. DR GO; GO:0043616; P:keratinocyte proliferation; IEA:Ensembl. DR GO; GO:0060173; P:limb development; IEA:Ensembl. DR GO; GO:0060644; P:mammary gland epithelial cell differentiation; ISS:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0010839; P:negative regulation of keratinocyte proliferation; IEA:Ensembl. DR GO; GO:2000647; P:negative regulation of stem cell proliferation; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0060021; P:roof of mouth development; IEA:Ensembl. DR GO; GO:0072089; P:stem cell proliferation; IEA:Ensembl. DR CDD; cd00103; IRF; 1. DR Gene3D; 2.60.200.10; -; 1. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 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-like_dom_sf. DR InterPro; IPR008984; SMAD_FHA_dom_sf. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR InterPro; IPR036390; WH_DNA-bd_sf. DR PANTHER; PTHR11949; INTERFERON REGULATORY FACTOR; 1. DR PANTHER; PTHR11949:SF9; INTERFERON REGULATORY FACTOR 6; 1. DR Pfam; PF00605; IRF; 1. DR Pfam; PF10401; IRF-3; 1. DR PRINTS; PR00267; INTFRNREGFCT. DR SMART; SM00348; IRF; 1. DR SMART; SM01243; IRF-3; 1. DR SUPFAM; SSF49879; SMAD/FHA domain; 1. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. DR PROSITE; PS00601; IRF_1; 1. DR PROSITE; PS51507; IRF_2; 1. DR Genevisible; O14896; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cytoplasm; Differentiation; Disease variant; KW DNA-binding; Nucleus; Reference proteome; Transcription; KW Transcription regulation; Ubl conjugation. FT CHAIN 1..467 FT /note="Interferon regulatory factor 6" FT /id="PRO_0000154560" FT DNA_BIND 7..115 FT /note="IRF tryptophan pentad repeat" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00840" FT REGION 121..156 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 1..95 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046435" FT VARIANT 2 FT /note="A -> V (in VWS1; dbSNP:rs28942093)" FT /evidence="ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:12920575" FT /id="VAR_014961" FT VARIANT 6 FT /note="R -> C (in VWS1; dbSNP:rs28942094)" FT /evidence="ECO:0000269|PubMed:12920575" FT /id="VAR_030046" FT VARIANT 16 FT /note="A -> V (in VWS1)" FT /evidence="ECO:0000269|PubMed:14640121" FT /id="VAR_030047" FT VARIANT 18 FT /note="V -> A (in VWS1; abrogates DNA binding)" FT /evidence="ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739" FT /id="VAR_014962" FT VARIANT 18 FT /note="V -> M (in VWS1; abrogates DNA binding; FT dbSNP:rs2077940645)" FT /evidence="ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739" FT /id="VAR_014963" FT VARIANT 22 FT /note="L -> P (in VWS1 and PPS; abrogates DNA binding; FT dbSNP:rs387906967)" FT /evidence="ECO:0000269|PubMed:14640121, FT ECO:0000269|PubMed:19036739" FT /id="VAR_030048" FT VARIANT 39 FT /note="P -> A (in VWS1)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014964" FT VARIANT 45 FT /note="R -> Q (in VWS1; dbSNP:rs121434229)" FT /evidence="ECO:0000269|PubMed:14618417" FT /id="VAR_030049" FT VARIANT 60 FT /note="W -> G (in PPS; abrogates DNA binding)" FT /evidence="ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739" FT /id="VAR_014965" FT VARIANT 61 FT /note="A -> G (in VWS1)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014966" FT VARIANT 64 FT /note="T -> I (in VWS1)" FT /evidence="ECO:0000269|PubMed:14640121" FT /id="VAR_030050" FT VARIANT 66 FT /note="K -> T (in PPS)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014967" FT VARIANT 70 FT /note="G -> R (in VWS1; does not affect DNA binding; FT dbSNP:rs776236749)" FT /evidence="ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739" FT /id="VAR_014968" FT VARIANT 76 FT /note="P -> S (in VWS1; abrogates DNA binding; FT dbSNP:rs886039388)" FT /evidence="ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739" FT /id="VAR_014969" FT VARIANT 82 FT /note="Q -> K (in PPS)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014970" FT VARIANT 84 FT /note="R -> C (in PPS; abrogates DNA binding; FT dbSNP:rs121434226)" FT /evidence="ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739" FT /id="VAR_014971" FT VARIANT 84 FT /note="R -> G (in VWS1; abrogates DNA binding)" FT /evidence="ECO:0000269|PubMed:15300989, FT ECO:0000269|PubMed:19036739" FT /id="VAR_030051" FT VARIANT 84 FT /note="R -> H (in PPS; abrogates DNA binding; FT dbSNP:rs121434227)" FT /evidence="ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739" FT /id="VAR_014972" FT VARIANT 84 FT /note="R -> L (in PPS; dbSNP:rs121434227)" FT /evidence="ECO:0000269|PubMed:20803643" FT /id="VAR_064475" FT VARIANT 88 FT /note="N -> H (in VWS1)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014973" FT VARIANT 89 FT /note="K -> E (in PPS; abrogates DNA binding)" FT /evidence="ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739" FT /id="VAR_014974" FT VARIANT 90 FT /note="S -> G (in VWS1)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014975" FT VARIANT 98 FT /note="D -> H (in VWS1; abrogates DNA binding; FT dbSNP:rs1571983348)" FT /evidence="ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:19036739" FT /id="VAR_014976" FT VARIANT 100 FT /note="T -> A (in VWS1)" FT /evidence="ECO:0000269|PubMed:14640121" FT /id="VAR_030052" FT VARIANT 250 FT /note="R -> Q (in VWS1; dbSNP:rs1553247774)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014977" FT VARIANT 251 FT /note="L -> P (in VWS1)" FT /evidence="ECO:0000269|PubMed:14640121" FT /id="VAR_030053" FT VARIANT 273 FT /note="Q -> R (in VWS1)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014978" FT VARIANT 274 FT /note="V -> I (3% in European-descended and 22% in Asian FT populations; responsible for 12% of the genetic FT contribution to cleft lip or palate; tripled the risk of FT recurrence in families that already had 1 affected child; FT dbSNP:rs2235371)" FT /evidence="ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:14702039, ECO:0000269|Ref.2" FT /id="VAR_014979" FT VARIANT 290..296 FT /note="FTSKLLD -> L (in VWS1)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014980" FT VARIANT 294 FT /note="L -> P (in VWS1)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014981" FT VARIANT 297 FT /note="V -> I (in VWS1; dbSNP:rs779827384)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014982" FT VARIANT 320 FT /note="K -> E (in VWS1)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014983" FT VARIANT 321 FT /note="V -> M (in VWS1)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014984" FT VARIANT 325 FT /note="G -> E (in VWS1)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014985" FT VARIANT 339 FT /note="R -> I (in VWS1; dbSNP:rs121434231)" FT /evidence="ECO:0000269|PubMed:18478600" FT /id="VAR_059080" FT VARIANT 345 FT /note="L -> P (in VWS1)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014986" FT VARIANT 347 FT /note="C -> F (in VWS1)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014987" FT VARIANT 349 FT /note="E -> V (in VWS1)" FT /evidence="ECO:0000269|PubMed:17122170" FT /id="VAR_030054" FT VARIANT 369 FT /note="F -> S (in VWS1 and OFC6; dbSNP:rs1185412313)" FT /evidence="ECO:0000269|PubMed:12219090, FT ECO:0000269|PubMed:21082654" FT /id="VAR_014988" FT VARIANT 374 FT /note="C -> W (in VWS1)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014989" FT VARIANT 388 FT /note="K -> E (in VWS1)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014990" FT VARIANT 396 FT /note="P -> S (in VWS1; dbSNP:rs121434230)" FT /evidence="ECO:0000269|PubMed:14618417" FT /id="VAR_030055" FT VARIANT 400 FT /note="R -> W (in VWS1; dbSNP:rs28942095)" FT /evidence="ECO:0000269|PubMed:12920575" FT /id="VAR_030056" FT VARIANT 424 FT /note="S -> L (in PPS; significant decrease of FT transcriptional activity; dbSNP:rs387906968)" FT /evidence="ECO:0000269|PubMed:20803643" FT /id="VAR_064476" FT VARIANT 430 FT /note="D -> N (in PPS)" FT /evidence="ECO:0000269|PubMed:12219090" FT /id="VAR_014991" FT VARIANT 439 FT /note="L -> P (in PPS; uncertain significance; FT dbSNP:rs886038202)" FT /evidence="ECO:0000269|PubMed:25691407" FT /id="VAR_085700" 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 //