IRF6_HUMAN
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 03-AUG-2022, entry version 200.
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}.
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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; 10.
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; O14896; -.
DR PeptideAtlas; O14896; -.
DR PRIDE; O14896; -.
DR ProteomicsDB; 24251; -.
DR ProteomicsDB; 48286; -. [O14896-1]
DR TopDownProteomics; O14896-1; -. [O14896-1]
DR Antibodypedia; 20702; 434 antibodies from 40 providers.
DR DNASU; 3664; -.
DR Ensembl; ENST00000367021.8; ENSP00000355988.3; ENSG00000117595.12. [O14896-1]
DR Ensembl; ENST00000542854.5; ENSP00000440532.1; ENSG00000117595.12. [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 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; DEVKLWP; -.
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; 5 hits in 1097 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 149 other tissues.
DR ExpressionAtlas; O14896; baseline and differential.
DR Genevisible; O14896; HS.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
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; 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-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 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; SSF46785; SSF46785; 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; 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 /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; unknown pathological 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
