Reviewed, UniProtKB/Swiss-Prot P52945 (PDX1_HUMAN)

Names and origin

Protein names

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

Gene names

Name:	PDX1
Synonyms:	IPF1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	283 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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. 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.
Subcellular location	Nucleus.
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.
Involvement in disease	Defects in PDX1 are a cause of pancreatic agenesis [MIM:260370]. This 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. Defects in PDX1 are the cause of maturity onset diabetes noninsulin-dependent diabetes mellitus (NIDDM) [MIM:125853]; also known as diabetes mellitus type II. Defects in PDX1 are the cause of maturity onset diabetes of the young type 4 (MODY4) [MIM:606392]; also symbolized MODY-4. MODY [MIM:606391] is a form of diabetes mellitus characterized by an autosomal dominant mode of inheritance, age of onset of 25 years or younger and a primary defect in insulin secretion.
Miscellaneous	According to Ref.7, 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	Nucleus
Coding sequence diversity	Polymorphism
Disease	Diabetes mellitus Disease mutation
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Activator Developmental protein
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	generation of precursor metabolites and energy Traceable author statement. Source: ProtInc insulin secretion Inferred from direct assay. Source: UniProtKB nitric oxide mediated signal transduction Inferred from direct assay. Source: UniProtKB organ morphogenesis Traceable author statement. Source: ProtInc
Cellular component	nucleus Inferred from electronic annotation. Source: InterPro
Molecular function	sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro specific RNA polymerase II transcription factor activity Traceable author statement. Source: ProtInc transcription factor activity Inferred from electronic annotation. Source: InterPro
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
Natural variations
	Natural variant	18	1	C → R in MODY4.		VAR_009309
	Natural variant	59	1	Q → L in MODY4.		VAR_009310
	Natural variant	76	1	D → N in MODY4; could be a polymorphism.		VAR_009311
	Natural variant	197	1	R → H in MODY4.		VAR_009312
	Natural variant	243	1	P → PP in MODY4.		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)
	P52945-1 [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

[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: 7590740] [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: 8635654] [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. 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. 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.
[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: 9252422] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Pancreatic islet.
[7]	"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: 16141209] [Abstract] Cited for: INTERACTION WITH SETD7.
[8]	"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: 10545530] [Abstract] Cited for: VARIANTS MODY4 ARG-18; ASN-76 AND HIS-197.
[9]	"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: 10545531] [Abstract] Cited for: VARIANTS MODY4 LEU-59; ASN-76 AND PRO-243 INS.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
PIR	G01926.
RefSeq	NP_000200.1.
UniGene	Hs.32938
3D structure databases
HSSP	HSSP built from PDB template 9ANT based on UniProtKB P02833.
SMR	P52945. Positions 148-205.
ModBase	Search...
PTM databases
PhosphoSite	P52945.
Genome annotation databases
Ensembl	ENSG00000139515. Homo sapiens. [Contig view]
GeneID	3651.
KEGG	hsa:3651.
Organism-specific databases
H-InvDB	HIX0037361.
HGNC	HGNC:6107. PDX1.
MIM	125853. phenotype. 260370. phenotype. 600733. gene. 606392. phenotype.
Orphanet	224. Diabetes mellitus, neonatal. 552. MODY syndrome. 2805. Pancreas agenesis.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	P52945.
Gene expression databases
ArrayExpress	P52945.
CleanEx	HS_PDX1.
GermOnline	ENSG00000139515. Homo sapiens.
Family and domain databases
InterPro	IPR001827. Antennapedia. IPR001356. Homeobox. IPR012287. Homeodomain-rel. IPR000047. HTH_lambrepressr. [Graphical view]
Gene3D	G3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
Pfam	PF00046. Homeobox. 1 hit. [Graphical view]
PRINTS	PR00025. ANTENNAPEDIA. PR00024. HOMEOBOX. PR00031. HTHREPRESSR.
ProDom	PD000010. Homeobox. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00389. HOX. 1 hit. [Graphical view]
PROSITE	PS00032. ANTENNAPEDIA. False negative. PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	14279.
SOURCE	Search...

Entry information

Entry name

PDX1_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 25, 2008
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)