PDX1_MOUSE
ID PDX1_MOUSE Reviewed; 284 AA.
AC P52946; Q3ZB03;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Pancreas/duodenum homeobox protein 1;
DE AltName: Full=Insulin promoter factor 1;
DE Short=IPF-1;
DE AltName: Full=Islet/duodenum homeobox 1;
DE Short=IDX-1;
DE AltName: Full=Somatostatin-transactivating factor 1;
DE Short=STF-1;
GN Name=Pdx1; Synonyms=Ipf1;
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].
RX PubMed=7901001; DOI=10.1002/j.1460-2075.1993.tb06109.x;
RA Ohlsson H., Karlsson K., Edlund T.;
RT "IPF1, a homeodomain-containing transactivator of the insulin gene.";
RL EMBO J. 12:4251-4259(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cecum;
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 MRNA].
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 [4]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH MEIS2 AND PBX1.
RX PubMed=9710595; DOI=10.1128/mcb.18.9.5109;
RA Swift G.H., Liu Y., Rose S.D., Bischof L.J., Steelman S., Buchberg A.M.,
RA Wright C.V., MacDonald R.J.;
RT "An endocrine-exocrine switch in the activity of the pancreatic homeodomain
RT protein PDX1 through formation of a trimeric complex with PBX1b and MRG1
RT (MEIS2).";
RL Mol. Cell. Biol. 18:5109-5120(1998).
RN [5]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH MEIS2 AND PBX1.
RX PubMed=11279116; DOI=10.1074/jbc.m100678200;
RA Liu Y., MacDonald R.J., Swift G.H.;
RT "DNA binding and transcriptional activation by a PDX1.PBX1b.MEIS2b trimer
RT and cooperation with a pancreas-specific basic helix-loop-helix complex.";
RL J. Biol. Chem. 276:17985-17993(2001).
RN [6]
RP INTERACTION WITH SPOP.
RC STRAIN=BALB/cJ; TISSUE=Pancreas;
RX PubMed=15121856; DOI=10.1128/mcb.24.10.4372-4383.2004;
RA Liu A., Desai B.M., Stoffers D.A.;
RT "Identification of PCIF1, a POZ domain protein that inhibits PDX-1 (MODY4)
RT transcriptional activity.";
RL Mol. Cell. Biol. 24:4372-4383(2004).
RN [7]
RP FUNCTION, AND INDUCTION.
RX PubMed=12219087; DOI=10.1038/ng890;
RA Nakae J., Biggs W.H. III, Kitamura T., Cavenee W.K., Wright C.V.,
RA Arden K.C., Accili D.;
RT "Regulation of insulin action and pancreatic beta-cell function by mutated
RT alleles of the gene encoding forkhead transcription factor Foxo1.";
RL Nat. Genet. 32:245-253(2002).
RN [8]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-152, AND MUTAGENESIS OF
RP THR-152.
RX PubMed=17052199; DOI=10.1042/bst0340791;
RA An R., da Silva Xavier G., Hao H.X., Semplici F., Rutter J., Rutter G.A.;
RT "Regulation by Per-Arnt-Sim (PAS) kinase of pancreatic duodenal homeobox-1
RT nuclear import in pancreatic beta-cells.";
RL Biochem. Soc. Trans. 34:791-793(2006).
RN [9]
RP PHOSPHORYLATION AT SER-269 BY HIPK2, AND MUTAGENESIS OF SER-269.
RX PubMed=20637728; DOI=10.1016/j.bbrc.2010.07.035;
RA An R., da Silva Xavier G., Semplici F., Vakhshouri S., Hao H.X., Rutter J.,
RA Pagano M.A., Meggio F., Pinna L.A., Rutter G.A.;
RT "Pancreatic and duodenal homeobox 1 (PDX1) phosphorylation at serine-269 is
RT HIPK2-dependent and affects PDX1 subnuclear localization.";
RL Biochem. Biophys. Res. Commun. 399:155-161(2010).
CC -!- FUNCTION: Activates insulin and somatostatin gene transcription. Key
CC regulator of islet peptide hormone expression but also responsible for
CC the development of the pancreas, most probably by determining
CC maturation and differentiation of common pancreatic precursor cells in
CC the developing gut. As part of a PDX1:PBX1b:MEIS2b complex in
CC pancreatic acinar cells is involved in the transcriptional activation
CC of the ELA1 enhancer; the complex binds to the enhancer B element and
CC cooperates with the transcription factor 1 complex (PTF1) bound to the
CC enhancer A element. Binds the DNA sequence 5'-CC[CT]TAATGGG-3'.
CC {ECO:0000269|PubMed:11279116, ECO:0000269|PubMed:12219087,
CC ECO:0000269|PubMed:9710595}.
CC -!- SUBUNIT: Interacts with the basic helix-loop-helix domains of TCF3(E47)
CC and NEUROD1 and with HMG-I(Y). Interacts with the methyltransferase
CC SETD7 (By similarity). Interacts with SPOP. Part of a PDX1:PBX1b:MEIS2b
CC complex. {ECO:0000250, ECO:0000269|PubMed:11279116,
CC ECO:0000269|PubMed:15121856, ECO:0000269|PubMed:9710595}.
CC -!- INTERACTION:
CC P52946; P13405: Rb1; NbExp=2; IntAct=EBI-7128945, EBI-971782;
CC P52946; Q6ZWS8: Spop; NbExp=5; IntAct=EBI-7128945, EBI-7128920;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000269|PubMed:17052199}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:17052199}.
CC -!- TISSUE SPECIFICITY: Duodenum and pancreas (Langerhans islet beta cells
CC and small subsets of endocrine non-beta-cells, at low levels in acinar
CC cells).
CC -!- DEVELOPMENTAL STAGE: At 8.5 dpc, detected in the gut epithelium from
CC which the pancreatic buds are formed. Transient expression in
CC pancreatic ducts, endocrine and acinar cells. Down-regulated around
CC 10.5 dpc when expression becomes restricted to differentiated beta-
CC cells.
CC -!- INDUCTION: Expression is repressed by FOXO1 in pancreatic beta-cells.
CC {ECO:0000269|PubMed:12219087}.
CC -!- DOMAIN: The Antp-type hexapeptide mediates heterodimerization with PBX
CC on a regulatory element of the somatostatin promoter. {ECO:0000250}.
CC -!- DOMAIN: The homeodomain, which contains the nuclear localization
CC signal, not only mediates DNA-binding, but also acts as a protein-
CC protein interaction domain for TCF3(E47), NEUROD1 and HMG-I(Y).
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated by the SAPK2 pathway at high intracellular glucose
CC concentration. Phosphorylated by HIPK2 on Ser-269 upon glucose
CC accumulation. This phosphorylation mediates subnuclear localization
CC shifting. Phosphorylation by PASK may lead to translocation into the
CC cytosol. {ECO:0000269|PubMed:17052199, ECO:0000269|PubMed:20637728}.
CC -!- SIMILARITY: Belongs to the Antp homeobox family. IPF1/XlHbox-8
CC subfamily. {ECO:0000305}.
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DR EMBL; X74342; CAA52389.1; -; mRNA.
DR EMBL; AK020261; BAB32045.1; -; mRNA.
DR EMBL; BC103572; AAI03573.1; -; mRNA.
DR EMBL; BC103581; AAI03582.1; -; mRNA.
DR EMBL; BC103582; AAI03583.1; -; mRNA.
DR EMBL; BC105642; AAI05643.1; -; mRNA.
DR CCDS; CCDS39398.1; -.
DR PIR; S39581; S39581.
DR RefSeq; NP_032840.1; NM_008814.3.
DR AlphaFoldDB; P52946; -.
DR SMR; P52946; -.
DR BioGRID; 202101; 5.
DR CORUM; P52946; -.
DR IntAct; P52946; 2.
DR MINT; P52946; -.
DR STRING; 10090.ENSMUSP00000082729; -.
DR iPTMnet; P52946; -.
DR PhosphoSitePlus; P52946; -.
DR PaxDb; P52946; -.
DR PeptideAtlas; P52946; -.
DR PRIDE; P52946; -.
DR ProteomicsDB; 287995; -.
DR Antibodypedia; 22687; 901 antibodies from 39 providers.
DR DNASU; 18609; -.
DR Ensembl; ENSMUST00000085591; ENSMUSP00000082729; ENSMUSG00000029644.
DR GeneID; 18609; -.
DR KEGG; mmu:18609; -.
DR UCSC; uc009any.2; mouse.
DR CTD; 3651; -.
DR MGI; MGI:102851; Pdx1.
DR VEuPathDB; HostDB:ENSMUSG00000029644; -.
DR eggNOG; KOG0489; Eukaryota.
DR GeneTree; ENSGT00940000162542; -.
DR HOGENOM; CLU_087401_0_0_1; -.
DR InParanoid; P52946; -.
DR OMA; HTWKGQW; -.
DR OrthoDB; 1102286at2759; -.
DR PhylomeDB; P52946; -.
DR TreeFam; TF326223; -.
DR BioGRID-ORCS; 18609; 4 hits in 74 CRISPR screens.
DR PRO; PR:P52946; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P52946; protein.
DR Bgee; ENSMUSG00000029644; Expressed in pancreas primordium and 47 other tissues.
DR Genevisible; P52946; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016607; C:nuclear speck; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IC:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; ISO:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0007417; P:central nervous system development; IEA:Ensembl.
DR GO; GO:0051594; P:detection of glucose; ISO:MGI.
DR GO; GO:0048565; P:digestive tract development; IMP:MGI.
DR GO; GO:0031018; P:endocrine pancreas development; IMP:MGI.
DR GO; GO:0035883; P:enteroendocrine cell differentiation; IMP:MGI.
DR GO; GO:0050673; P:epithelial cell proliferation; IMP:MGI.
DR GO; GO:0031017; P:exocrine pancreas development; IMP:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
DR GO; GO:0006006; P:glucose metabolic process; IDA:MGI.
DR GO; GO:0030073; P:insulin secretion; ISO:MGI.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IMP:MGI.
DR GO; GO:0001889; P:liver development; IMP:MGI.
DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; IMP:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:MGI.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:2000675; P:negative regulation of type B pancreatic cell apoptotic process; IMP:MGI.
DR GO; GO:0007263; P:nitric oxide mediated signal transduction; ISO:MGI.
DR GO; GO:0031016; P:pancreas development; IMP:MGI.
DR GO; GO:0010942; P:positive regulation of cell death; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0043388; P:positive regulation of DNA binding; ISO:MGI.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IDA:UniProtKB.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:MGI.
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; IDA:MGI.
DR GO; GO:1904692; P:positive regulation of type B pancreatic cell proliferation; IMP:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IDA:MGI.
DR GO; GO:0010468; P:regulation of gene expression; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0043279; P:response to alkaloid; IEA:Ensembl.
DR GO; GO:0010157; P:response to chlorate; IEA:Ensembl.
DR GO; GO:0034097; P:response to cytokine; IEA:Ensembl.
DR GO; GO:0070542; P:response to fatty acid; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose; ISO:MGI.
DR GO; GO:0010040; P:response to iron(II) ion; IEA:Ensembl.
DR GO; GO:0043201; P:response to leucine; IEA:Ensembl.
DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl.
DR GO; GO:0033273; P:response to vitamin; IEA:Ensembl.
DR GO; GO:0009611; P:response to wounding; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; ISO:MGI.
DR GO; GO:0048863; P:stem cell differentiation; ISO:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0006351; P:transcription, DNA-templated; ISO:MGI.
DR GO; GO:0060290; P:transdifferentiation; IEA:Ensembl.
DR GO; GO:0097050; P:type B pancreatic cell apoptotic process; IMP:MGI.
DR GO; GO:0003309; P:type B pancreatic cell differentiation; IMP:MGI.
DR GO; GO:0044342; P:type B pancreatic cell proliferation; IMP:MGI.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017995; Homeobox_antennapedia.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR020479; Homeobox_metazoa.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00025; ANTENNAPEDIA.
DR PRINTS; PR00024; HOMEOBOX.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Activator; Cytoplasm; Developmental protein; Diabetes mellitus;
KW DNA-binding; Homeobox; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..284
FT /note="Pancreas/duodenum homeobox protein 1"
FT /id="PRO_0000049149"
FT DNA_BIND 147..206
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 13..73
FT /note="Transactivation domain"
FT /evidence="ECO:0000250"
FT REGION 30..116
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 202..284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 119..124
FT /note="Antp-type hexapeptide"
FT MOTIF 198..204
FT /note="Nuclear localization signal"
FT COMPBIAS 37..51
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 152
FT /note="Phosphothreonine; by PASK"
FT /evidence="ECO:0000269|PubMed:17052199"
FT MOD_RES 269
FT /note="Phosphoserine; by HIPK2"
FT /evidence="ECO:0000269|PubMed:20637728"
FT MUTAGEN 152
FT /note="T->D,E: Displays a more cytosolic distribution."
FT /evidence="ECO:0000269|PubMed:17052199"
FT MUTAGEN 269
FT /note="S->A: Reduced phosphorylation by HIPK2."
FT /evidence="ECO:0000269|PubMed:20637728"
FT MUTAGEN 269
FT /note="S->E: Abnormal subnuclear localization upon glucose
FT accumulation."
FT /evidence="ECO:0000269|PubMed:20637728"
SQ SEQUENCE 284 AA; 30999 MW; A57D04569D14E3C4 CRC64;
MNSEEQYYAA TQLYKDPCAF QRGPVPEFSA NPPACLYMGR QPPPPPPPQF TSSLGSLEQG
SPPDISPYEV PPLASDDPAG AHLHHHLPAQ LGLAHPPPGP FPNGTEPGGL EEPNRVQLPF
PWMKSTKAHA WKGQWAGGAY TAEPEENKRT RTAYTRAQLL ELEKEFLFNK YISRPRRVEL
AVMLNLTERH IKIWFQNRRM KWKKEEDKKR SSGTPSGGGG GEEPEQDCAV TSGEELLAVP
PLPPPGGAVP PGVPAAVREG LLPSGLSVSP QPSSIAPLRP QEPR
