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Pancreas/duodenum homeobox protein 1 (PDX-1) (Glucose-sensitive factor) (GSF) (Insulin promoter factor 1) (IPF-1) (Insulin upstream factor 1) (IUF-1) (Islet/duodenum homeobox-1) (IDX-1) (Somatostatin-transactivating factor 1) (STF-1)

 PDX1_HUMAN              Reviewed;         283 AA.
P52945; O60594; Q5VYW2;
01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
01-OCT-1996, sequence version 1.
22-NOV-2017, entry version 175.
RecName: Full=Pancreas/duodenum homeobox protein 1;
Short=PDX-1;
AltName: Full=Glucose-sensitive factor;
Short=GSF;
AltName: Full=Insulin promoter factor 1;
Short=IPF-1;
AltName: Full=Insulin upstream factor 1;
Short=IUF-1;
AltName: Full=Islet/duodenum homeobox-1;
Short=IDX-1;
AltName: Full=Somatostatin-transactivating factor 1;
Short=STF-1;
Name=PDX1; Synonyms=IPF1, STF1;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=7590740; DOI=10.1006/geno.1995.1120;
Stoffel M., Stein R., Wright C.V., Espinosa R. III, le Beau M.M.,
Bell G.I.;
"Localization of human homeodomain transcription factor insulin
promoter factor 1 (IPF1) to chromosome band 13q12.1.";
Genomics 28:125-126(1995).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
TISSUE=Pancreatic islet;
PubMed=8635654; DOI=10.2337/diab.45.6.789;
Inoue H., Riggs A.C., Tanizawa Y., Ueda K., Kuwano A., Liu L.,
Donis-Keller H., Permutt M.A.;
"Isolation, characterization, and chromosomal mapping of the human
insulin promoter factor 1 (IPF-1) gene.";
Diabetes 45:789-794(1996).
[3]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Pancreatic islet;
Hiroshi I.;
Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Pancreatic islet;
Marshak S., Totary H., Cerasi E., Melloul D.;
Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Hara M., Lindner T.H., Paz V.P., Wang X., Iwasaki N., Bell G.I.;
Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Pancreatic islet;
PubMed=9252422; DOI=10.1074/jbc.272.33.20936;
Macfarlane W.M., Smith S.B., James R.F., Clifton A.D., Doza Y.N.,
Cohen P., Docherty K.;
"The p38/reactivating kinase mitogen-activated protein kinase cascade
mediates the activation of the transcription factor insulin upstream
factor 1 and insulin gene transcription by high glucose in pancreatic
beta-cells.";
J. Biol. Chem. 272:20936-20944(1997).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15057823; DOI=10.1038/nature02379;
Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E.,
Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E.,
Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.,
Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R.,
Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S.,
Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M.,
Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J.,
Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E.,
Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L.,
Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J.,
Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S.,
Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J.,
Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M.,
King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A.,
Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S.,
Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I.,
Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S.,
Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A.,
Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B.,
Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L.,
Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M.,
Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.;
"The DNA sequence and analysis of human chromosome 13.";
Nature 428:522-528(2004).
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[9]
INVOLVEMENT IN PAGEN1.
PubMed=8988180; DOI=10.1038/ng0197-106;
Stoffers D.A., Zinkin N.T., Stanojevic V., Clarke W.L., Habener J.F.;
"Pancreatic agenesis attributable to a single nucleotide deletion in
the human IPF1 gene coding sequence.";
Nat. Genet. 15:106-110(1997).
[10]
INTERACTION WITH SETD7.
PubMed=16141209; DOI=10.1074/jbc.M505741200;
Francis J., Chakrabarti S.K., Garmey J.C., Mirmira R.G.;
"Pdx-1 links histone H3-Lys-4 methylation to RNA polymerase II
elongation during activation of insulin transcription.";
J. Biol. Chem. 280:36244-36253(2005).
[11]
PHOSPHORYLATION AT SER-268 BY HIPK2.
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).
[12]
VARIANTS MODY4 ARG-18; ASN-76 AND HIS-197.
PubMed=10545530; DOI=10.1172/JCI7449;
Macfarlane W.M., Frayling T.M., Ellard S., Evans J.C., Allen L.I.,
Bulman M.P., Ayres S., Shepherd M., Clark P., Millward A., Demaine A.,
Wilkin T., Docherty K., Hattersley A.T.;
"Missense mutations in the insulin promoter factor-1 gene predispose
to type 2 diabetes.";
J. Clin. Invest. 104:R33-R39(1999).
[13]
VARIANTS MODY4 LEU-59; ASN-76 AND PRO-243 INS.
PubMed=10545531; DOI=10.1172/JCI7469;
Hani E.H., Stoffers D.A., Chevre J.-C., Durand E., Stanojevic V.,
Dina C., Habener J.F., Froguel P.;
"Defective mutations in the insulin promoter factor-1 (IPF-1) gene in
late-onset type 2 diabetes mellitus.";
J. Clin. Invest. 104:R41-R48(1999).
-!- FUNCTION: Activates insulin, somatostatin, glucokinase, islet
amyloid polypeptide and glucose transporter type 2 gene
transcription. Particularly involved in glucose-dependent
regulation of insulin gene transcription. 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 preferentially the DNA motif 5'-[CT]TAAT[TG]-3'.
During development, specifies the early pancreatic epithelium,
permitting its proliferation, branching and subsequent
differentiation. At adult stage, required for maintaining the
hormone-producing phenotype of the beta-cell.
-!- SUBUNIT: Interacts with the basic helix-loop-helix domains of
TCF3(E47) and NEUROD1 and with HMG-I(Y). Interacts with SPOP (By
similarity). Interacts with the methyltransferase SETD7. Part of a
PDX1:PBX1b:MEIS2b complex. {ECO:0000250,
ECO:0000269|PubMed:16141209}.
-!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytosol {ECO:0000250}.
-!- TISSUE SPECIFICITY: Duodenum and pancreas (Langerhans islet beta
cells and small subsets of endocrine non-beta-cells, at low levels
in acinar 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-268 upon
glucose accumulation. This phosphorylation mediates subnuclear
localization shifting. Phosphorylation by PASK may lead to
translocation into the cytosol (By similarity). {ECO:0000250}.
-!- DISEASE: Pancreatic agenesis 1 (PAGEN1) [MIM:260370]: A disease
characterized by isolated hypoplasia or agenesis of the pancreas,
pancreatic beta-cell failure resulting in neonatal insulin-
dependent diabetes mellitus, and exocrine pancreatic
insufficiency. {ECO:0000269|PubMed:8988180}. Note=The disease is
caused by mutations affecting the gene represented in this entry.
-!- DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM)
[MIM:125853]: A multifactorial disorder of glucose homeostasis
caused by a lack of sensitivity to the body's own insulin.
Affected individuals usually have an obese body habitus and
manifestations of a metabolic syndrome characterized by diabetes,
insulin resistance, hypertension and hypertriglyceridemia. The
disease results in long-term complications that affect the eyes,
kidneys, nerves, and blood vessels. Note=Disease susceptibility is
associated with variations affecting the gene represented in this
entry.
-!- DISEASE: Maturity-onset diabetes of the young 4 (MODY4)
[MIM:606392]: A form of diabetes that is characterized by an
autosomal dominant mode of inheritance, onset in childhood or
early adulthood (usually before 25 years of age), a primary defect
in insulin secretion and frequent insulin-independence at the
beginning of the disease. {ECO:0000269|PubMed:10545530,
ECO:0000269|PubMed:10545531}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- MISCELLANEOUS: According to PubMed:16141209, it may be methylated
by SETD7 in vitro. However, the relevance of methylation is unsure
in vivo.
-!- SIMILARITY: Belongs to the Antp homeobox family. IPF1/XlHbox-8
subfamily. {ECO:0000305}.
-!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
and Haematology;
URL="http://atlasgeneticsoncology.org/Genes/PDX1ID43921ch13q12.html";
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EMBL; U35632; AAA88820.1; -; mRNA.
EMBL; S82178; AAB47101.1; -; Genomic_DNA.
EMBL; S82168; AAB47101.1; JOINED; Genomic_DNA.
EMBL; U30329; AAA74012.1; -; mRNA.
EMBL; X99894; CAA68169.1; -; mRNA.
EMBL; AF035260; AAB88463.1; -; Genomic_DNA.
EMBL; AF035259; AAB88463.1; JOINED; Genomic_DNA.
EMBL; AF049893; AAC05157.1; -; mRNA.
EMBL; AL353195; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471075; EAX08420.1; -; Genomic_DNA.
CCDS; CCDS9327.1; -.
PIR; G01926; G01926.
RefSeq; NP_000200.1; NM_000209.3.
UniGene; Hs.32938; -.
ProteinModelPortal; P52945; -.
SMR; P52945; -.
BioGrid; 109860; 9.
ELM; P52945; -.
IntAct; P52945; 2.
MINT; MINT-1894661; -.
STRING; 9606.ENSP00000370421; -.
iPTMnet; P52945; -.
PhosphoSitePlus; P52945; -.
BioMuta; PDX1; -.
DMDM; 1708540; -.
PaxDb; P52945; -.
PeptideAtlas; P52945; -.
PRIDE; P52945; -.
DNASU; 3651; -.
Ensembl; ENST00000381033; ENSP00000370421; ENSG00000139515.
GeneID; 3651; -.
KEGG; hsa:3651; -.
UCSC; uc001urt.3; human.
CTD; 3651; -.
DisGeNET; 3651; -.
EuPathDB; HostDB:ENSG00000139515.5; -.
GeneCards; PDX1; -.
GeneReviews; PDX1; -.
HGNC; HGNC:6107; PDX1.
HPA; CAB025873; -.
HPA; HPA059146; -.
MalaCards; PDX1; -.
MIM; 125853; phenotype.
MIM; 260370; phenotype.
MIM; 600733; gene.
MIM; 606392; phenotype.
neXtProt; NX_P52945; -.
OpenTargets; ENSG00000139515; -.
Orphanet; 552; MODY.
Orphanet; 2805; Partial pancreatic agenesis.
Orphanet; 99885; Permanent neonatal diabetes mellitus.
PharmGKB; PA162399173; -.
eggNOG; KOG0489; Eukaryota.
eggNOG; ENOG410ZTBY; LUCA.
GeneTree; ENSGT00900000140772; -.
HOGENOM; HOG000115484; -.
HOVERGEN; HBG004525; -.
InParanoid; P52945; -.
KO; K07594; -.
OMA; PPPCLYM; -.
OrthoDB; EOG091G0GVH; -.
PhylomeDB; P52945; -.
TreeFam; TF326223; -.
Reactome; R-HSA-210745; Regulation of gene expression in beta cells.
Reactome; R-HSA-210747; Regulation of gene expression in early pancreatic precursor cells.
SignaLink; P52945; -.
SIGNOR; P52945; -.
GeneWiki; PDX1; -.
GenomeRNAi; 3651; -.
PRO; PR:P52945; -.
Proteomes; UP000005640; Chromosome 13.
Bgee; ENSG00000139515; -.
CleanEx; HS_PDX1; -.
Genevisible; P52945; HS.
GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
GO; GO:0016607; C:nuclear speck; IEA:Ensembl.
GO; GO:0005654; C:nucleoplasm; IDA:HPA.
GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
GO; GO:0001046; F:core promoter sequence-specific DNA binding; IEA:Ensembl.
GO; GO:0032403; F:protein complex binding; IEA:Ensembl.
GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IEA:Ensembl.
GO; GO:0003705; F:transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; IEA:Ensembl.
GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:BHF-UCL.
GO; GO:0008134; F:transcription factor binding; IEA:Ensembl.
GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc.
GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
GO; GO:0010260; P:animal organ senescence; IEA:Ensembl.
GO; GO:0007417; P:central nervous system development; IEA:Ensembl.
GO; GO:0051594; P:detection of glucose; ISS:BHF-UCL.
GO; GO:0048565; P:digestive tract development; IEA:Ensembl.
GO; GO:0031017; P:exocrine pancreas development; IEA:Ensembl.
GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc.
GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl.
GO; GO:0030073; P:insulin secretion; IDA:BHF-UCL.
GO; GO:0001889; P:liver development; IEA:Ensembl.
GO; GO:0016331; P:morphogenesis of embryonic epithelium; IEA:Ensembl.
GO; GO:0008285; P:negative regulation of cell proliferation; IEA:Ensembl.
GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IEA:Ensembl.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
GO; GO:2000675; P:negative regulation of type B pancreatic cell apoptotic process; IEA:Ensembl.
GO; GO:0007263; P:nitric oxide mediated signal transduction; IDA:BHF-UCL.
GO; GO:0010942; P:positive regulation of cell death; IEA:Ensembl.
GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl.
GO; GO:0043388; P:positive regulation of DNA binding; IEA:Ensembl.
GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:BHF-UCL.
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:0042493; P:response to drug; IEA:Ensembl.
GO; GO:0070542; P:response to fatty acid; IEA:Ensembl.
GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
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; IEA:Ensembl.
GO; GO:0048863; P:stem cell differentiation; IEA:Ensembl.
GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc.
GO; GO:0060290; P:transdifferentiation; IEA:Ensembl.
GO; GO:0003309; P:type B pancreatic cell differentiation; IDA:BHF-UCL.
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; Homeobox; 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; Disease mutation; DNA-binding; Homeobox; Nucleus;
Phosphoprotein; Polymorphism; Reference proteome; Transcription;
Transcription regulation.
CHAIN 1 283 Pancreas/duodenum homeobox protein 1.
/FTId=PRO_0000049147.
DNA_BIND 146 205 Homeobox. {ECO:0000255|PROSITE-
ProRule:PRU00108}.
REGION 13 73 Transactivation domain. {ECO:0000250}.
MOTIF 118 123 Antp-type hexapeptide.
MOTIF 197 203 Nuclear localization signal.
{ECO:0000250}.
COMPBIAS 42 51 Poly-Pro.
COMPBIAS 216 219 Poly-Gly.
COMPBIAS 239 244 Poly-Pro.
MOD_RES 151 151 Phosphothreonine; by PASK.
{ECO:0000250|UniProtKB:P52946}.
MOD_RES 268 268 Phosphoserine; by HIPK2.
{ECO:0000269|PubMed:20637728}.
VARIANT 18 18 C -> R (in MODY4; dbSNP:rs137852785).
{ECO:0000269|PubMed:10545530}.
/FTId=VAR_009309.
VARIANT 59 59 Q -> L (in MODY4; dbSNP:rs137852784).
{ECO:0000269|PubMed:10545531}.
/FTId=VAR_009310.
VARIANT 76 76 D -> N (in MODY4; unknown pathological
significance; dbSNP:rs137852783).
{ECO:0000269|PubMed:10545530,
ECO:0000269|PubMed:10545531}.
/FTId=VAR_009311.
VARIANT 197 197 R -> H (in MODY4; dbSNP:rs137852786).
{ECO:0000269|PubMed:10545530}.
/FTId=VAR_009312.
VARIANT 243 243 P -> PP (in MODY4).
{ECO:0000269|PubMed:10545531}.
/FTId=VAR_009313.
CONFLICT 56 56 A -> S (in Ref. 6; AAC05157).
{ECO:0000305}.
CONFLICT 116 116 Q -> H (in Ref. 6; AAC05157).
{ECO:0000305}.
CONFLICT 210 211 GG -> SS (in Ref. 6; AAC05157).
{ECO:0000305}.
SEQUENCE 283 AA; 30771 MW; 5D48EC8D3289F72B CRC64;
MNGEEQYYAA TQLYKDPCAF QRGPAPEFSA SPPACLYMGR QPPPPPPHPF PGALGALEQG
SPPDISPYEV PPLADDPAVA HLHHHLPAQL ALPHPPAGPF PEGAEPGVLE EPNRVQLPFP
WMKSTKAHAW KGQWAGGAYA AEPEENKRTR TAYTRAQLLE LEKEFLFNKY ISRPRRVELA
VMLNLTERHI KIWFQNRRMK WKKEEDKKRG GGTAVGGGGV AEPEQDCAVT SGEELLALPP
PPPPGGAVPP AAPVAAREGR LPPGLSASPQ PSSVAPRRPQ EPR


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15-288-22325F Homeobox protein TGIF2 - TGFB-induced factor 2; 5'-TG-3'-interacting factor 2; TGF(beta)-induced transcription factor 2 Polyclonal 0.05 mg


 

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