ID   IRF6_MOUSE              Reviewed;         467 AA.
AC   P97431; Q91VD0;
DT   13-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   27-MAR-2024, entry version 169.
DE   RecName: Full=Interferon regulatory factor 6;
DE            Short=IRF-6;
GN   Name=Irf6;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ; TISSUE=Colon;
RA   Grossman A., Mittrucker H.W., Antonio L., Mak T.W.;
RL   Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Kidney, and Oviduct;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary tumor;
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   [6]
RP   TISSUE SPECIFICITY.
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   [7]
RP   FUNCTION, AND MUTAGENESIS OF ARG-84.
RX   PubMed=17041603; DOI=10.1038/ng1894;
RA   Richardson R.J., Dixon J., Malhotra S., Hardman M.J., Knowles L.,
RA   Boot-Handford R.P., Shore P., Whitmarsh A., Dixon M.J.;
RT   "Irf6 is a key determinant of the keratinocyte proliferation-
RT   differentiation switch.";
RL   Nat. Genet. 38:1329-1334(2006).
RN   [8]
RP   FUNCTION.
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   FUNCTION, DNA-BINDING, SUBUNIT, AND SUBCELLULAR LOCATION.
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   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Pancreas;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [11]
RP   FUNCTION.
RX   PubMed=21574244; DOI=10.1002/ajmg.a.33980;
RA   Rorick N.K., Kinoshita A., Weirather J.L., Peyrard-Janvid M., de Lima R.L.,
RA   Dunnwald M., Shanske A.L., Moretti-Ferreira D., Koillinen H., Kere J.,
RA   Mansilla M.A., Murray J.C., Goudy S.L., Schutte B.C.;
RT   "Genomic strategy identifies a missense mutation in WD-repeat domain 65
RT   (WDR65) in an individual with Van der Woude syndrome.";
RL   Am. J. Med. Genet. A 155:1314-1321(2011).
CC   -!- FUNCTION: Probable DNA-binding transcriptional activator. Key
CC       determinant of the keratinocyte proliferation-differentiation switch
CC       involved in appropriate epidermal development. Plays a role in
CC       regulating mammary epithelial cell proliferation. May regulate WDR65
CC       transcription. {ECO:0000269|PubMed:17041603,
CC       ECO:0000269|PubMed:18212048, ECO:0000269|PubMed:19036739,
CC       ECO:0000269|PubMed:21574244}.
CC   -!- SUBUNIT: Interacts with SERPINB5. {ECO:0000250}.
CC   -!- INTERACTION:
CC       P97431; P37238: Pparg; NbExp=2; IntAct=EBI-21183505, EBI-5260705;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. Cytoplasm
CC       {ECO:0000269|PubMed:19036739}. Note=Translocates to nucleus in response
CC       to an activating signal. {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: High levels of expression along the medial edge of
CC       the fusing palate, tooth buds, hair follicles, genitalia and skin.
CC       {ECO:0000269|PubMed:12219090}.
CC   -!- PTM: Phosphorylated. Phosphorylation status depends on the cell cycle
CC       and is a signal for ubiquitination and proteasome-mediated degradation.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the IRF family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00840}.
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DR   EMBL; U73029; AAB36714.1; -; mRNA.
DR   EMBL; AK143299; BAE25338.1; -; mRNA.
DR   EMBL; AK143954; BAE25628.1; -; mRNA.
DR   EMBL; AL365322; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH466555; EDL12956.1; -; Genomic_DNA.
DR   EMBL; BC008515; AAH08515.1; -; mRNA.
DR   CCDS; CCDS15632.1; -.
DR   RefSeq; NP_058547.2; NM_016851.2.
DR   RefSeq; XP_006497325.1; XM_006497262.3.
DR   RefSeq; XP_006497326.1; XM_006497263.3.
DR   AlphaFoldDB; P97431; -.
DR   SMR; P97431; -.
DR   IntAct; P97431; 1.
DR   STRING; 10090.ENSMUSP00000075839; -.
DR   iPTMnet; P97431; -.
DR   PhosphoSitePlus; P97431; -.
DR   EPD; P97431; -.
DR   MaxQB; P97431; -.
DR   PaxDb; 10090-ENSMUSP00000075839; -.
DR   PeptideAtlas; P97431; -.
DR   ProteomicsDB; 267153; -.
DR   Antibodypedia; 20702; 498 antibodies from 40 providers.
DR   DNASU; 54139; -.
DR   Ensembl; ENSMUST00000076521.7; ENSMUSP00000075839.6; ENSMUSG00000026638.16.
DR   GeneID; 54139; -.
DR   KEGG; mmu:54139; -.
DR   UCSC; uc007edy.1; mouse.
DR   AGR; MGI:1859211; -.
DR   CTD; 3664; -.
DR   MGI; MGI:1859211; Irf6.
DR   VEuPathDB; HostDB:ENSMUSG00000026638; -.
DR   eggNOG; ENOG502QRNT; Eukaryota.
DR   GeneTree; ENSGT00940000157451; -.
DR   HOGENOM; CLU_031544_0_1_1; -.
DR   InParanoid; P97431; -.
DR   OMA; NEAWPKE; -.
DR   OrthoDB; 3740806at2759; -.
DR   PhylomeDB; P97431; -.
DR   TreeFam; TF328512; -.
DR   BioGRID-ORCS; 54139; 2 hits in 79 CRISPR screens.
DR   PRO; PR:P97431; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; P97431; Protein.
DR   Bgee; ENSMUSG00000026638; Expressed in substantia propria of cornea and 206 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IMP:MGI.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
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; ISO:MGI.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0048468; P:cell development; IMP:MGI.
DR   GO; GO:0008283; P:cell population proliferation; IGI:MGI.
DR   GO; GO:1904888; P:cranial skeletal system development; IMP:MGI.
DR   GO; GO:0002376; P:immune system process; IBA:GO_Central.
DR   GO; GO:0030216; P:keratinocyte differentiation; IMP:MGI.
DR   GO; GO:0043616; P:keratinocyte proliferation; IMP:MGI.
DR   GO; GO:0060173; P:limb development; IMP:MGI.
DR   GO; GO:0060644; P:mammary gland epithelial cell differentiation; IEP:UniProtKB.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR   GO; GO:0010839; P:negative regulation of keratinocyte proliferation; IGI:MGI.
DR   GO; GO:2000647; P:negative regulation of stem cell proliferation; IGI:MGI.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0060021; P:roof of mouth development; IMP:MGI.
DR   GO; GO:0043588; P:skin development; IMP:MGI.
DR   GO; GO:0072089; P:stem cell proliferation; IGI:MGI.
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; P97431; MM.
PE   1: Evidence at protein level;
KW   Cytoplasm; Differentiation; DNA-binding; Nucleus; Reference proteome;
KW   Transcription; Transcription regulation; Ubl conjugation.
FT   CHAIN           1..467
FT                   /note="Interferon regulatory factor 6"
FT                   /id="PRO_0000154561"
FT   DNA_BIND        7..115
FT                   /note="IRF tryptophan pentad repeat"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00840"
FT   REGION          121..155
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MUTAGEN         84
FT                   /note="R->C: Mice show an atypical limb development, are
FT                   covered by an abnormal smooth skin and die shortly after
FT                   birth. The esophageal lumen is obliterated by adhesion of
FT                   the stratified, squamous epithelium lining this structure.
FT                   The hindlimbs, tail and body are fused together by a
FT                   thickened epidermis. Epidermis is hyperproliferative but
FT                   does not undergo a normal differentiation program."
FT                   /evidence="ECO:0000269|PubMed:17041603"
FT   CONFLICT        119
FT                   /note="T -> P (in Ref. 1; AAB36714)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   467 AA;  53111 MW;  1C564BC8D79C5259 CRC64;
     MALHPRRVRL KPWLVAQVDS GLYPGLIWLH RDSKRFQIPW KHATRHSPQQ EEENTIFKAW
     AVETGKYQEG VDDPDPAKWK AQLRCALNKS REFNLMYDGT KEVPMNPVKI YQVCDIPQTQ
     GSVINPGSTG SAPWDEKDND VDEDEEEDEL EQSQHHVPIQ DTFPFLNING SPMAPASVGN
     CSVGNCSPES VWPKTEPLEM EVPQAPIQPF YSSPELWISS LPMTDLDIKF QYRGKEYGQT
     MTVSNPQGCR LFYGDLGPMP DQEELFGPVS LEQVKFPGPE HITNEKQKLF TSKLLDVMDR
     GLILEVSGHA IYAIRLCQCK VYWSGPCAPS LAAPNLIERQ KKVKLFCLET FLSELIAHQK
     GQIEKQPPFE IYLCFGEEWP DGKPLERKLI LVQVIPVVAR MIYEMFSGDF TRSFDSGSVR
     LQISTPDIKD NIVAQLKQLY RILQTQESWQ PMQPAPSMQL PQALPAQ
//