ID   PAX4_MOUSE              Reviewed;         349 AA.
AC   P32115; B7ZNC7; P97341; Q9QUR1; Q9R091;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2000, sequence version 2.
DT   24-JAN-2024, entry version 185.
DE   RecName: Full=Paired box protein Pax-4;
GN   Name=Pax4; Synonyms=Pax-4;
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] (ISOFORMS 1; 2 AND 3).
RC   TISSUE=Insulinoma;
RX   PubMed=9480859; DOI=10.1006/bbrc.1998.8144;
RA   Inoue H., Nomiyama J., Nakai K., Matsutani A., Tanizawa Y., Oka Y.;
RT   "Isolation of full-length cDNA of mouse PAX4 gene and identification of its
RT   human homologue.";
RL   Biochem. Biophys. Res. Commun. 243:628-633(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Insulinoma;
RX   PubMed=9439631; DOI=10.1006/bbrc.1997.7935;
RA   Matsushita T., Yamaoka T., Otsuka S., Moritani M., Matsumoto T.,
RA   Itakura M.;
RT   "Molecular cloning of mouse paired-box-containing gene (Pax-4) from an
RT   islet beta cell line and deduced sequence of human Pax-4.";
RL   Biochem. Biophys. Res. Commun. 242:176-180(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND MUTAGENESIS OF
RP   272-GLU-PRO-273.
RX   PubMed=10364449; DOI=10.1006/bbrc.1999.0809;
RA   Kalousova A., Benes V., Paces J., Paces V., Kozmik Z.;
RT   "DNA binding and transactivating properties of the paired and homeobox
RT   protein Pax4.";
RL   Biochem. Biophys. Res. Commun. 259:510-518(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Insulinoma;
RX   PubMed=10567553; DOI=10.1128/mcb.19.12.8281;
RA   Fujitani Y., Kajimoto Y., Yasuda T., Matsuoka T.-A., Kaneto H.,
RA   Umayahara Y., Fujita N., Watada H., Miyazaki J., Yamasaki Y.;
RT   "Identification of a portable repression domain and an E1A-responsive
RT   activation domain in Pax4: a possible role of Pax4 as a transcriptional
RT   repressor in the pancreas.";
RL   Mol. Cell. Biol. 19:8281-8291(1999).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Insulinoma;
RX   PubMed=10567552; DOI=10.1128/mcb.19.12.8272;
RA   Smith S.B., Ee H.C., Conners J.R., German M.S.;
RT   "Paired-homeodomain transcription factor PAX4 acts as a transcriptional
RT   repressor in early pancreatic development.";
RL   Mol. Cell. Biol. 19:8272-8280(1999).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Brain;
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   NUCLEOTIDE SEQUENCE OF 6-132.
RX   PubMed=1685142; DOI=10.1016/0888-7543(91)90151-4;
RA   Walther C., Guenet J.-L., Simon D., Deutsch U., Jostes B., Goulding M.D.,
RA   Plachov D., Balling R., Gruss P.;
RT   "Pax: a murine multigene family of paired box-containing genes.";
RL   Genomics 11:424-434(1991).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 34-237.
RC   STRAIN=NMRI; TISSUE=Embryo;
RX   PubMed=9121556; DOI=10.1038/386399a0;
RA   Sosa-Pineda B., Chowdhury K., Torres M., Oliver G., Gruss P.;
RT   "The Pax4 gene is essential for differentiation of insulin-producing beta
RT   cells in the mammalian pancreas.";
RL   Nature 386:399-402(1997).
CC   -!- FUNCTION: Plays an important role in the differentiation and
CC       development of pancreatic islet beta cells. Transcriptional repressor
CC       that competes with PAX6 in binding to a common element in the glucagon,
CC       insulin and somatostatin promoters.
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P32115-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P32115-2; Sequence=VSP_002361;
CC       Name=3;
CC         IsoId=P32115-3; Sequence=VSP_002362;
CC   -!- TISSUE SPECIFICITY: Expressed in early pancreas. Later restricted to
CC       beta cells. Undetectable in adult islets.
CC   -!- SIMILARITY: Belongs to the paired homeobox family. {ECO:0000305}.
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DR   EMBL; AF031150; AAC40046.1; -; mRNA.
DR   EMBL; AB008912; BAA24505.1; -; mRNA.
DR   EMBL; AB010557; BAA24516.1; -; mRNA.
DR   EMBL; AB010558; BAA24517.1; -; mRNA.
DR   EMBL; AF145233; AAF03533.1; -; mRNA.
DR   EMBL; AF142321; AAF03530.1; -; Genomic_DNA.
DR   EMBL; BC145168; AAI45169.1; -; mRNA.
DR   EMBL; AF104231; AAF14073.1; -; mRNA.
DR   EMBL; Y09584; CAA70772.1; -; mRNA.
DR   CCDS; CCDS39447.1; -. [P32115-1]
DR   CCDS; CCDS51732.1; -. [P32115-2]
DR   PIR; A41061; A41061.
DR   PIR; JC5827; JC5827.
DR   PIR; JC5961; JC5961.
DR   PIR; JC5962; JC5962.
DR   RefSeq; NP_001153397.1; NM_001159925.1. [P32115-2]
DR   RefSeq; NP_001153398.1; NM_001159926.1.
DR   RefSeq; NP_035168.1; NM_011038.2. [P32115-1]
DR   RefSeq; XP_017176939.1; XM_017321450.1.
DR   AlphaFoldDB; P32115; -.
DR   SMR; P32115; -.
DR   STRING; 10090.ENSMUSP00000031718; -.
DR   PhosphoSitePlus; P32115; -.
DR   PaxDb; 10090-ENSMUSP00000031718; -.
DR   Antibodypedia; 1766; 367 antibodies from 36 providers.
DR   DNASU; 18506; -.
DR   Ensembl; ENSMUST00000031718.14; ENSMUSP00000031718.8; ENSMUSG00000029706.16. [P32115-1]
DR   Ensembl; ENSMUST00000164519.9; ENSMUSP00000131301.2; ENSMUSG00000029706.16. [P32115-2]
DR   GeneID; 18506; -.
DR   KEGG; mmu:18506; -.
DR   UCSC; uc009bcs.2; mouse. [P32115-1]
DR   UCSC; uc012eit.1; mouse. [P32115-2]
DR   AGR; MGI:97488; -.
DR   CTD; 5078; -.
DR   MGI; MGI:97488; Pax4.
DR   VEuPathDB; HostDB:ENSMUSG00000029706; -.
DR   eggNOG; KOG0849; Eukaryota.
DR   GeneTree; ENSGT00940000161709; -.
DR   HOGENOM; CLU_019281_1_2_1; -.
DR   InParanoid; P32115; -.
DR   OMA; RYYRTGI; -.
DR   OrthoDB; 5398393at2759; -.
DR   PhylomeDB; P32115; -.
DR   TreeFam; TF320146; -.
DR   BioGRID-ORCS; 18506; 2 hits in 76 CRISPR screens.
DR   PRO; PR:P32115; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   RNAct; P32115; Protein.
DR   Bgee; ENSMUSG00000029706; Expressed in entorhinal cortex and 30 other cell types or tissues.
DR   ExpressionAtlas; P32115; baseline and differential.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005667; C:transcription regulator complex; TAS:MGI.
DR   GO; GO:0003677; F:DNA binding; IDA:MGI.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:MGI.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR   GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR   GO; GO:0009887; P:animal organ morphogenesis; TAS:MGI.
DR   GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR   GO; GO:0030858; P:positive regulation of epithelial cell differentiation; IMP:MGI.
DR   GO; GO:0045595; P:regulation of cell differentiation; IMP:MGI.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; TAS:MGI.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR   GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl.
DR   GO; GO:0003309; P:type B pancreatic cell differentiation; IMP:MGI.
DR   CDD; cd00086; homeodomain; 1.
DR   Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR   Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 2.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR043182; PAIRED_DNA-bd_dom.
DR   InterPro; IPR001523; Paired_dom.
DR   InterPro; IPR043565; PAX_fam.
DR   InterPro; IPR036388; WH-like_DNA-bd_sf.
DR   PANTHER; PTHR45636:SF8; PAIRED BOX PROTEIN PAX-4; 1.
DR   PANTHER; PTHR45636; PAIRED BOX PROTEIN PAX-6-RELATED-RELATED; 1.
DR   Pfam; PF00046; Homeodomain; 1.
DR   Pfam; PF00292; PAX; 1.
DR   PRINTS; PR00027; PAIREDBOX.
DR   SMART; SM00389; HOX; 1.
DR   SMART; SM00351; PAX; 1.
DR   SUPFAM; SSF46689; Homeodomain-like; 2.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   PROSITE; PS00034; PAIRED_1; 1.
DR   PROSITE; PS51057; PAIRED_2; 1.
DR   Genevisible; P32115; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Developmental protein; Differentiation; DNA-binding;
KW   Homeobox; Nucleus; Paired box; Reference proteome; Repressor;
KW   Transcription; Transcription regulation.
FT   CHAIN           1..349
FT                   /note="Paired box protein Pax-4"
FT                   /id="PRO_0000050181"
FT   DNA_BIND        5..131
FT                   /note="Paired"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00381"
FT   DNA_BIND        170..229
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          8..64
FT                   /note="PAI subdomain"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00381"
FT   REGION          83..131
FT                   /note="RED subdomain"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00381"
FT   REGION          278..349
FT                   /note="Transcription repression"
FT   VAR_SEQ         239..251
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:9480859"
FT                   /id="VSP_002361"
FT   VAR_SEQ         278..314
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:9480859"
FT                   /id="VSP_002362"
FT   MUTAGEN         272..273
FT                   /note="EP->DL: Loss of transactivation function."
FT                   /evidence="ECO:0000269|PubMed:10364449"
FT   CONFLICT        175
FT                   /note="T -> A (in Ref. 8; CAA70772)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        277
FT                   /note="S -> P (in Ref. 5; AAF14073)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   349 AA;  38008 MW;  215E0469F46DF49B CRC64;
     MQQDGLSSVN QLGGLFVNGR PLPLDTRQQI VQLAIRGMRP CDISRSLKVS NGCVSKILGR
     YYRTGVLEPK CIGGSKPRLA TPAVVARIAQ LKDEYPALFA WEIQHQLCTE GLCTQDKAPS
     VSSINRVLRA LQEDQSLHWT QLRSPAVLAP VLPSPHSNCG APRGPHPGTS HRNRTIFSPG
     QAEALEKEFQ RGQYPDSVAR GKLAAATSLP EDTVRVWFSN RRAKWRRQEK LKWEAQLPGA
     SQDLTVPKNS PGIISAQQSP GSVPSAALPV LEPLSPSFCQ LCCGTAPGRC SSDTSSQAYL
     QPYWDCQSLL PVASSSYVEF AWPCLTTHPV HHLIGGPGQV PSTHCSNWP
//