PAX4_MOUSE
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 03-AUG-2022, entry version 178.
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; P32115; -.
DR PRIDE; P32115; -.
DR Antibodypedia; 1766; 337 antibodies from 36 providers.
DR DNASU; 18506; -.
DR Ensembl; ENSMUST00000031718; ENSMUSP00000031718; ENSMUSG00000029706. [P32115-1]
DR Ensembl; ENSMUST00000164519; ENSMUSP00000131301; ENSMUSG00000029706. [P32115-2]
DR GeneID; 18506; -.
DR KEGG; mmu:18506; -.
DR UCSC; uc009bcs.2; mouse. [P32115-1]
DR UCSC; uc012eit.1; mouse. [P32115-2]
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 PhylomeDB; P32115; -.
DR TreeFam; TF320146; -.
DR BioGRID-ORCS; 18506; 2 hits in 71 CRISPR screens.
DR PRO; PR:P32115; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P32115; protein.
DR Bgee; ENSMUSG00000029706; Expressed in entorhinal cortex and 28 other tissues.
DR ExpressionAtlas; P32115; baseline and differential.
DR Genevisible; P32115; MM.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
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:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
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:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:MGI.
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; 1.10.10.10; -; 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; IPR033559; Pax-4.
DR InterPro; IPR043565; PAX_fam.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR PANTHER; PTHR45636; PTHR45636; 1.
DR PANTHER; PTHR45636:SF8; PTHR45636:SF8; 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; SSF46689; 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.
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
