P52945 (PDX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pancreas/duodenum homeobox protein 1
Short name=PDX-1

Alternative name(s):
Glucose-sensitive factor
Short name=GSF
Insulin promoter factor 1
Short name=IPF-1
Insulin upstream factor 1
Short name=IUF-1
Islet/duodenum homeobox-1
Short name=IDX-1
Somatostatin-transactivating factor 1
Short name=STF-1

Gene names

Name:	PDX1
Synonyms:	IPF1, STF1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	283 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 structure	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. Ref.10
Subcellular location	Nucleus. Cytoplasm › cytosol By similarity.
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 By similarity. 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) By similarity.
Post-translational modification	Phosphorylated by the SAPK2 pathway at high intracellular glucose concentration. Phosphorylated by HIPK2 on Ser-268 upon glucose accumulation. This phoyphorylation mediates subnuclear localization shifting. Phosphorylation by PASK may lead to translocation into the cytosol By similarity. Ref.11
Involvement in disease	Pancreatic agenesis, congenital (PAGEN) [MIM:260370]: Autosomal recessive disorder is characterized by absence or hypoplasia of pancreas, leading to early-onset insulin-dependent diabetes mellitus. This was found in a frameshift mutation that produces a truncated protein and results in a second initiation that produces a second protein that act as a dominant negative mutant. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 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. 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.13
Miscellaneous	According to Ref.10, it may be methylated by SETD7 in vitro. However, the relevance of methylation is unsure in vivo.
Sequence similarities	Belongs to the Antp homeobox family. IPF1/XlHbox-8 subfamily. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Diabetes mellitus Disease mutation
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Activator Developmental protein
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	central nervous system development Inferred from electronic annotation. Source: Compara detection of glucose Inferred from sequence or structural similarity. Source: BHF-UCL digestive tract development Inferred from electronic annotation. Source: Compara exocrine pancreas development Inferred from electronic annotation. Source: Compara generation of precursor metabolites and energy Traceable author statement PubMed 8954967. Source: ProtInc glucose homeostasis Inferred from electronic annotation. Source: Compara glucose metabolic process Inferred from electronic annotation. Source: Compara insulin secretion Inferred from direct assay PubMed 17941991. Source: BHF-UCL liver development Inferred from electronic annotation. Source: Compara morphogenesis of embryonic epithelium Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara nitric oxide mediated signal transduction Inferred from direct assay PubMed 17941991. Source: BHF-UCL organ morphogenesis Traceable author statement Ref.9. Source: ProtInc organ regeneration Inferred from electronic annotation. Source: Compara organ senescence Inferred from electronic annotation. Source: Compara positive regulation of DNA binding Inferred from electronic annotation. Source: Compara positive regulation of cell death Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of insulin secretion Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: BHF-UCL response to chlorate Inferred from electronic annotation. Source: Compara response to cytokine stimulus Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to fatty acid Inferred from electronic annotation. Source: Compara response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara response to leucine Inferred from electronic annotation. Source: Compara response to nicotine Inferred from electronic annotation. Source: Compara response to vitamin Inferred from electronic annotation. Source: Compara response to wounding Inferred from electronic annotation. Source: Compara smoothened signaling pathway Inferred from electronic annotation. Source: Compara stem cell differentiation Inferred from electronic annotation. Source: Compara transcription from RNA polymerase II promoter Traceable author statement PubMed 8954967. Source: ProtInc transdifferentiation Inferred from electronic annotation. Source: Compara type B pancreatic cell differentiation Inferred from direct assay PubMed 12124776. Source: BHF-UCL
Cellular_component	cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	chromatin binding Inferred from electronic annotation. Source: Compara core promoter sequence-specific DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding transcription factor activity Traceable author statement PubMed 17941991. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 283	283	Pancreas/duodenum homeobox protein 1		PRO_0000049147
Regions
	DNA binding	146 – 205	60	Homeobox
	Region	13 – 73	61	Transactivation domain By similarity
	Motif	118 – 123	6	Antp-type hexapeptide
	Motif	197 – 203	7	Nuclear localization signal By similarity
	Compositional bias	42 – 51	10	Poly-Pro
	Compositional bias	216 – 219	4	Poly-Gly
	Compositional bias	239 – 244	6	Poly-Pro
Amino acid modifications
	Modified residue	151	1	Phosphothreonine; by PASK By similarity
	Modified residue	268	1	Phosphoserine; by HIPK2 Ref.11
Natural variations
	Natural variant	18	1	C → R in MODY4. Ref.12		VAR_009309
	Natural variant	59	1	Q → L in MODY4. Ref.13		VAR_009310
	Natural variant	76	1	D → N in MODY4; unknown pathological significance. Ref.12 Ref.13		VAR_009311
	Natural variant	197	1	R → H in MODY4. Ref.12		VAR_009312
	Natural variant	243	1	P → PP in MODY4. Ref.13		VAR_009313
Experimental info
	Sequence conflict	56	1	A → S in AAC05157. Ref.6
	Sequence conflict	116	1	Q → H in AAC05157. Ref.6
	Sequence conflict	210 – 211	2	GG → SS in AAC05157. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	P52945 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 5D48EC8D3289F72B	FASTA	283	30,771
	10 20 30 40 50 60 MNGEEQYYAA TQLYKDPCAF QRGPAPEFSA SPPACLYMGR QPPPPPPHPF PGALGALEQG 70 80 90 100 110 120 SPPDISPYEV PPLADDPAVA HLHHHLPAQL ALPHPPAGPF PEGAEPGVLE EPNRVQLPFP 130 140 150 160 170 180 WMKSTKAHAW KGQWAGGAYA AEPEENKRTR TAYTRAQLLE LEKEFLFNKY ISRPRRVELA 190 200 210 220 230 240 VMLNLTERHI KIWFQNRRMK WKKEEDKKRG GGTAVGGGGV AEPEQDCAVT SGEELLALPP 250 260 270 280 PPPPGGAVPP AAPVAAREGR LPPGLSASPQ PSSVAPRRPQ EPR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Localization of human homeodomain transcription factor insulin promoter factor 1 (IPF1) to chromosome band 13q12.1." Stoffel M., Stein R., Wright C.V., Espinosa R. III, le Beau M.M., Bell G.I. Genomics 28:125-126(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Isolation, characterization, and chromosomal mapping of the human insulin promoter factor 1 (IPF-1) gene." Inoue H., Riggs A.C., Tanizawa Y., Ueda K., Kuwano A., Liu L., Donis-Keller H., Permutt M.A. Diabetes 45:789-794(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Pancreatic islet.
[3]	Hiroshi I. Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Pancreatic islet.
[4]	Marshak S., Totary H., Cerasi E., Melloul D. Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Pancreatic islet.
[5]	Hara M., Lindner T.H., Paz V.P., Wang X., Iwasaki N., Bell G.I. Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"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." Macfarlane W.M., Smith S.B., James R.F., Clifton A.D., Doza Y.N., Cohen P., Docherty K. J. Biol. Chem. 272:20936-20944(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Pancreatic islet.
[7]	"The DNA sequence and analysis of human chromosome 13." 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. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	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 Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence." Stoffers D.A., Zinkin N.T., Stanojevic V., Clarke W.L., Habener J.F. Nat. Genet. 15:106-110(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PAGEN.
[10]	"Pdx-1 links histone H3-Lys-4 methylation to RNA polymerase II elongation during activation of insulin transcription." Francis J., Chakrabarti S.K., Garmey J.C., Mirmira R.G. J. Biol. Chem. 280:36244-36253(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SETD7.
[11]	"Pancreatic and duodenal homeobox 1 (PDX1) phosphorylation at serine-269 is HIPK2-dependent and affects PDX1 subnuclear localization." 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. Biochem. Biophys. Res. Commun. 399:155-161(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-268 BY HIPK2.
[12]	"Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetes." 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. J. Clin. Invest. 104:R33-R39(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MODY4 ARG-18; ASN-76 AND HIS-197.
[13]	"Defective mutations in the insulin promoter factor-1 (IPF-1) gene in late-onset type 2 diabetes mellitus." Hani E.H., Stoffers D.A., Chevre J.-C., Durand E., Stanojevic V., Dina C., Habener J.F., Froguel P. J. Clin. Invest. 104:R41-R48(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MODY4 LEU-59; ASN-76 AND PRO-243 INS.
+	Additional computationally mapped references.

Web resources

GeneReviews

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	U35632 mRNA. Translation: AAA88820.1. S82178, S82168 Genomic DNA. Translation: AAB47101.1. U30329 mRNA. Translation: AAA74012.1. X99894 mRNA. Translation: CAA68169.1. AF035260, AF035259 Genomic DNA. Translation: AAB88463.1. AF049893 mRNA. Translation: AAC05157.1. AL353195 Genomic DNA. Translation: CAH72544.1. CH471075 Genomic DNA. Translation: EAX08420.1.
IPI	IPI00006036.
PIR	G01926.
RefSeq	NP_000200.1. NM_000209.3.
UniGene	Hs.32938.
3D structure databases
ProteinModelPortal	P52945.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1894661.
STRING	9606.ENSP00000370421.
PTM databases
PhosphoSite	P52945.
Polymorphism databases
DMDM	1708540.
Proteomic databases
PaxDb	P52945.
PRIDE	P52945.
Protocols and materials databases
DNASU	3651.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000381033; ENSP00000370421; ENSG00000139515.
GeneID	3651.
KEGG	hsa:3651.
UCSC	uc001urt.2. human.
Organism-specific databases
CTD	3651.
GeneCards	GC13P028494.
HGNC	HGNC:6107. PDX1.
HPA	CAB025873.
MIM	125853. phenotype. 260370. phenotype. 600733. gene. 606392. phenotype.
neXtProt	NX_P52945.
Orphanet	552. MODY syndrome. 2805. Partial pancreatic agenesis. 99885. Permanent neonatal diabetes mellitus.
PharmGKB	PA162399173.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG271681.
HOGENOM	HOG000115484.
HOVERGEN	HBG004525.
InParanoid	P52945.
KO	K07594.
OMA	PYEVPPI.
OrthoDB	EOG4M0F2P.
PhylomeDB	P52945.
Enzyme and pathway databases
Pathway_Interaction_DB	hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.
Reactome	REACT_111045. Developmental Biology.
SignaLink	P52945.
Gene expression databases
Bgee	P52945.
CleanEx	HS_PDX1.
Genevestigator	P52945.
GermOnline	ENSG00000139515. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.60. 1 hit.
InterPro	IPR017995. Homeobox_antennapedia. IPR017970. Homeobox_CS. IPR020479. Homeobox_metazoa. IPR001356. Homeodomain. IPR009057. Homeodomain-like. [Graphical view]
Pfam	PF00046. Homeobox. 1 hit. [Graphical view]
PRINTS	PR00025. ANTENNAPEDIA. PR00024. HOMEOBOX.
SMART	SM00389. HOX. 1 hit. [Graphical view]
SUPFAM	SSF46689. Homeodomain_like. 1 hit.
PROSITE	PS00032. ANTENNAPEDIA. False negative. PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	3651.
NextBio	14279.
SOURCE	Search...

Entry information

Entry name

PDX1_HUMAN

Accession

Primary (citable) accession number: P52945
Secondary accession number(s): O60594, Q5VYW2

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 29, 2013
This is version 135 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.