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Pancreas/duodenum homeobox protein 1 (Insulin promoter factor 1) (IPF-1) (Islet/duodenum homeobox 1) (IDX-1) (Somatostatin-transactivating factor 1) (STF-1)

 PDX1_MOUSE              Reviewed;         284 AA.
P52946; Q3ZB03;
01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
01-OCT-1996, sequence version 1.
05-DEC-2018, entry version 167.
RecName: Full=Pancreas/duodenum homeobox protein 1;
AltName: Full=Insulin promoter factor 1;
Short=IPF-1;
AltName: Full=Islet/duodenum homeobox 1;
Short=IDX-1;
AltName: Full=Somatostatin-transactivating factor 1;
Short=STF-1;
Name=Pdx1; Synonyms=Ipf1;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=7901001;
Ohlsson H., Karlsson K., Edlund T.;
"IPF1, a homeodomain-containing transactivator of the insulin gene.";
EMBO J. 12:4251-4259(1993).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=C57BL/6J; TISSUE=Cecum;
PubMed=16141072; DOI=10.1126/science.1112014;
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
Hayashizaki Y.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH MEIS2 AND PBX1.
PubMed=9710595; DOI=10.1128/MCB.18.9.5109;
Swift G.H., Liu Y., Rose S.D., Bischof L.J., Steelman S.,
Buchberg A.M., Wright C.V., MacDonald R.J.;
"An endocrine-exocrine switch in the activity of the pancreatic
homeodomain protein PDX1 through formation of a trimeric complex with
PBX1b and MRG1 (MEIS2).";
Mol. Cell. Biol. 18:5109-5120(1998).
[5]
FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH MEIS2 AND PBX1.
PubMed=11279116; DOI=10.1074/jbc.M100678200;
Liu Y., MacDonald R.J., Swift G.H.;
"DNA binding and transcriptional activation by a PDX1.PBX1b.MEIS2b
trimer and cooperation with a pancreas-specific basic helix-loop-helix
complex.";
J. Biol. Chem. 276:17985-17993(2001).
[6]
INTERACTION WITH SPOP.
STRAIN=BALB/cJ; TISSUE=Pancreas;
PubMed=15121856; DOI=10.1128/MCB.24.10.4372-4383.2004;
Liu A., Desai B.M., Stoffers D.A.;
"Identification of PCIF1, a POZ domain protein that inhibits PDX-1
(MODY4) transcriptional activity.";
Mol. Cell. Biol. 24:4372-4383(2004).
[7]
SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-152, AND MUTAGENESIS OF
THR-152.
PubMed=17052199; DOI=10.1042/BST0340791;
An R., da Silva Xavier G., Hao H.X., Semplici F., Rutter J.,
Rutter G.A.;
"Regulation by Per-Arnt-Sim (PAS) kinase of pancreatic duodenal
homeobox-1 nuclear import in pancreatic beta-cells.";
Biochem. Soc. Trans. 34:791-793(2006).
[8]
PHOSPHORYLATION AT SER-269 BY HIPK2, AND MUTAGENESIS OF SER-269.
PubMed=20637728; DOI=10.1016/j.bbrc.2010.07.035;
An R., da Silva Xavier G., Semplici F., Vakhshouri S., Hao H.X.,
Rutter J., Pagano M.A., Meggio F., Pinna L.A., Rutter G.A.;
"Pancreatic and duodenal homeobox 1 (PDX1) phosphorylation at serine-
269 is HIPK2-dependent and affects PDX1 subnuclear localization.";
Biochem. Biophys. Res. Commun. 399:155-161(2010).
-!- FUNCTION: Activates insulin and somatostatin gene transcription.
Key regulator of islet peptide hormone expression but also
responsible for the development of the pancreas, most probably by
determining maturation and differentiation of common pancreatic
precursor cells in the developing gut. As part of a
PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells is involved
in the transcriptional activation of the ELA1 enhancer; the
complex binds to the enhancer B element and cooperates with the
transcription factor 1 complex (PTF1) bound to the enhancer A
element. Binds the DNA sequence 5'-CC[CT]TAATGGG-3'.
{ECO:0000269|PubMed:11279116, ECO:0000269|PubMed:9710595}.
-!- SUBUNIT: Interacts with the basic helix-loop-helix domains of
TCF3(E47) and NEUROD1 and with HMG-I(Y). Interacts with the
methyltransferase SETD7 (By similarity). Interacts with SPOP. Part
of a PDX1:PBX1b:MEIS2b complex. {ECO:0000250,
ECO:0000269|PubMed:11279116, ECO:0000269|PubMed:15121856,
ECO:0000269|PubMed:9710595}.
-!- INTERACTION:
P13405:Rb1; NbExp=2; IntAct=EBI-7128945, EBI-971782;
Q6ZWS8:Spop; NbExp=5; IntAct=EBI-7128945, EBI-7128920;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00108, ECO:0000269|PubMed:17052199}. Cytoplasm, cytosol
{ECO:0000269|PubMed:17052199}.
-!- TISSUE SPECIFICITY: Duodenum and pancreas (Langerhans islet beta
cells and small subsets of endocrine non-beta-cells, at low levels
in acinar cells).
-!- DEVELOPMENTAL STAGE: At 8.5 dpc, detected in the gut epithelium
from which the pancreatic buds are formed. Transient expression in
pancreatic ducts, endocrine and acinar cells. Down-regulated
around 10.5 dpc when expression becomes restricted to
differentiated beta-cells.
-!- DOMAIN: The Antp-type hexapeptide mediates heterodimerization with
PBX on a regulatory element of the somatostatin promoter.
{ECO:0000250}.
-!- DOMAIN: The homeodomain, which contains the nuclear localization
signal, not only mediates DNA-binding, but also acts as a protein-
protein interaction domain for TCF3(E47), NEUROD1 and HMG-I(Y).
{ECO:0000250}.
-!- PTM: Phosphorylated by the SAPK2 pathway at high intracellular
glucose concentration. Phosphorylated by HIPK2 on Ser-269 upon
glucose accumulation. This phosphorylation mediates subnuclear
localization shifting. Phosphorylation by PASK may lead to
translocation into the cytosol. {ECO:0000269|PubMed:17052199,
ECO:0000269|PubMed:20637728}.
-!- SIMILARITY: Belongs to the Antp homeobox family. IPF1/XlHbox-8
subfamily. {ECO:0000305}.
-----------------------------------------------------------------------
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-----------------------------------------------------------------------
EMBL; X74342; CAA52389.1; -; mRNA.
EMBL; AK020261; BAB32045.1; -; mRNA.
EMBL; BC103572; AAI03573.1; -; mRNA.
EMBL; BC103581; AAI03582.1; -; mRNA.
EMBL; BC103582; AAI03583.1; -; mRNA.
EMBL; BC105642; AAI05643.1; -; mRNA.
CCDS; CCDS39398.1; -.
PIR; S39581; S39581.
RefSeq; NP_032840.1; NM_008814.3.
UniGene; Mm.389714; -.
ProteinModelPortal; P52946; -.
SMR; P52946; -.
BioGrid; 202101; 5.
CORUM; P52946; -.
IntAct; P52946; 2.
MINT; P52946; -.
STRING; 10090.ENSMUSP00000082729; -.
iPTMnet; P52946; -.
PhosphoSitePlus; P52946; -.
PaxDb; P52946; -.
PeptideAtlas; P52946; -.
PRIDE; P52946; -.
Ensembl; ENSMUST00000085591; ENSMUSP00000082729; ENSMUSG00000029644.
GeneID; 18609; -.
KEGG; mmu:18609; -.
UCSC; uc009any.2; mouse.
CTD; 3651; -.
MGI; MGI:102851; Pdx1.
eggNOG; KOG0489; Eukaryota.
eggNOG; ENOG410ZTBY; LUCA.
GeneTree; ENSGT00940000162542; -.
HOGENOM; HOG000115484; -.
HOVERGEN; HBG004525; -.
InParanoid; P52946; -.
KO; K07594; -.
OMA; PPPCLYM; -.
OrthoDB; EOG091G0GVH; -.
PhylomeDB; P52946; -.
TreeFam; TF326223; -.
PRO; PR:P52946; -.
Proteomes; UP000000589; Chromosome 5.
Bgee; ENSMUSG00000029644; Expressed in 76 organ(s), highest expression level in islet of Langerhans.
CleanEx; MM_PDX1; -.
Genevisible; P52946; MM.
GO; GO:0005737; C:cytoplasm; ISO:MGI.
GO; GO:0005829; C:cytosol; TAS:Reactome.
GO; GO:0016607; C:nuclear speck; IDA:MGI.
GO; GO:0005654; C:nucleoplasm; ISO:MGI.
GO; GO:0005634; C:nucleus; IDA:MGI.
GO; GO:0003682; F:chromatin binding; IDA:MGI.
GO; GO:0003677; F:DNA binding; IDA:MGI.
GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
GO; GO:1990841; F:promoter-specific chromatin binding; ISO:MGI.
GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
GO; GO:0001077; F:proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific; IC:NTNU_SB.
GO; GO:0000978; F:RNA polymerase II proximal promoter sequence-specific DNA binding; IDA:NTNU_SB.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
GO; GO:0003705; F:transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; IEA:Ensembl.
GO; GO:0008134; F:transcription factor binding; ISO:MGI.
GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
GO; GO:0010260; P:animal organ senescence; IEA:Ensembl.
GO; GO:0030154; P:cell differentiation; IMP:MGI.
GO; GO:0007417; P:central nervous system development; IEA:Ensembl.
GO; GO:0051594; P:detection of glucose; ISO:MGI.
GO; GO:0048565; P:digestive tract development; IMP:MGI.
GO; GO:0031018; P:endocrine pancreas development; IMP:MGI.
GO; GO:0031017; P:exocrine pancreas development; IMP:MGI.
GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
GO; GO:0006006; P:glucose metabolic process; IDA:MGI.
GO; GO:0030073; P:insulin secretion; ISO:MGI.
GO; GO:0001889; P:liver development; IMP:MGI.
GO; GO:0016331; P:morphogenesis of embryonic epithelium; IMP:MGI.
GO; GO:0008285; P:negative regulation of cell proliferation; IMP:MGI.
GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IMP:MGI.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
GO; GO:2000675; P:negative regulation of type B pancreatic cell apoptotic process; IMP:MGI.
GO; GO:0007263; P:nitric oxide mediated signal transduction; ISO:MGI.
GO; GO:0031016; P:pancreas development; IMP:MGI.
GO; GO:0010942; P:positive regulation of cell death; ISO:MGI.
GO; GO:0008284; P:positive regulation of cell proliferation; IMP:MGI.
GO; GO:0043388; P:positive regulation of DNA binding; ISO:MGI.
GO; GO:0032024; P:positive regulation of insulin secretion; ISO:MGI.
GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:MGI.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
GO; GO:0042127; P:regulation of cell proliferation; IDA:MGI.
GO; GO:0010468; P:regulation of gene expression; ISO:MGI.
GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
GO; GO:0043279; P:response to alkaloid; IEA:Ensembl.
GO; GO:0010157; P:response to chlorate; IEA:Ensembl.
GO; GO:0034097; P:response to cytokine; IEA:Ensembl.
GO; GO:0070542; P:response to fatty acid; IEA:Ensembl.
GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
GO; GO:0009749; P:response to glucose; ISO:MGI.
GO; GO:0010040; P:response to iron(II) ion; IEA:Ensembl.
GO; GO:0043201; P:response to leucine; IEA:Ensembl.
GO; GO:0035094; P:response to nicotine; IEA:Ensembl.
GO; GO:0033273; P:response to vitamin; IEA:Ensembl.
GO; GO:0009611; P:response to wounding; IEA:Ensembl.
GO; GO:0007224; P:smoothened signaling pathway; ISO:MGI.
GO; GO:0048863; P:stem cell differentiation; ISO:MGI.
GO; GO:0006366; P:transcription by RNA polymerase II; ISO:MGI.
GO; GO:0006351; P:transcription, DNA-templated; ISO:MGI.
GO; GO:0060290; P:transdifferentiation; IEA:Ensembl.
GO; GO:0003309; P:type B pancreatic cell differentiation; ISO:MGI.
CDD; cd00086; homeodomain; 1.
InterPro; IPR009057; Homeobox-like_sf.
InterPro; IPR017995; Homeobox_antennapedia.
InterPro; IPR017970; Homeobox_CS.
InterPro; IPR001356; Homeobox_dom.
InterPro; IPR020479; Homeobox_metazoa.
Pfam; PF00046; Homeodomain; 1.
PRINTS; PR00025; ANTENNAPEDIA.
PRINTS; PR00024; HOMEOBOX.
SMART; SM00389; HOX; 1.
SUPFAM; SSF46689; SSF46689; 1.
PROSITE; PS00027; HOMEOBOX_1; 1.
PROSITE; PS50071; HOMEOBOX_2; 1.
1: Evidence at protein level;
Activator; Complete proteome; Cytoplasm; Developmental protein;
Diabetes mellitus; DNA-binding; Homeobox; Nucleus; Phosphoprotein;
Reference proteome; Transcription; Transcription regulation.
CHAIN 1 284 Pancreas/duodenum homeobox protein 1.
/FTId=PRO_0000049149.
DNA_BIND 147 206 Homeobox. {ECO:0000255|PROSITE-
ProRule:PRU00108}.
REGION 13 73 Transactivation domain. {ECO:0000250}.
MOTIF 119 124 Antp-type hexapeptide.
MOTIF 198 204 Nuclear localization signal.
COMPBIAS 42 48 Poly-Pro.
COMPBIAS 217 221 Poly-Gly.
MOD_RES 152 152 Phosphothreonine; by PASK.
{ECO:0000269|PubMed:17052199}.
MOD_RES 269 269 Phosphoserine; by HIPK2.
{ECO:0000269|PubMed:20637728}.
MUTAGEN 152 152 T->D,E: Displays a more cytosolic
distribution.
{ECO:0000269|PubMed:17052199}.
MUTAGEN 269 269 S->A: Reduced phosphorylation by HIPK2.
{ECO:0000269|PubMed:20637728}.
MUTAGEN 269 269 S->E: Abnormal subnuclear localization
upon glucose accumulation.
{ECO:0000269|PubMed:20637728}.
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


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