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pancreas/duodenum homeobox protein 1; PDX-1; insulin promoter factor 1; IPF-1; Islet/duodenum homeobox-1; IDX-1; somatostatin-transactivating factor 1; STF-1; insulin upstream factor 1; IUF-1; glucose-sensitive factor; GSF (PDX1, IPF1)
Function:
- activates insulin, somatostatin, glucokinase, islet amyloid polypeptide & glucose transporter type 2 gene transcription
- especially involved in glucose-dependent regulation of insulin gene transcription
- binds preferentially the DNA motif 5'-[CT]TAAT[TG]-3'
- during development, specifies early pancreatic epithelium, permitting its proliferation, branching & subsequent differentiation
- at adult stage, required for maintaining the hormone- producing phenotype of the beta-cell
- phosphorylated by the SAPK2 pathway at high intracellular glucose concentration
- interacts with the basic helix-loop-helix domains of TCF3(E47) & NEUROD1 & with HMG-I(Y)
- interacts with SPOP
- interacts with the methyltransferase SETD7
Structure:
- the antp-type hexapeptide mediates heterodimerization with PBX on a regulatory element of the somatostatin promoter
- the homeodomain contains the nuclear localization signal
a) mediates DNA-binding
b) acts as a protein-protein interaction domain for TCF3(E47), NEUROD1 & HMG-I(Y)
- belongs to the antp homeobox family, IPF1/XlHbox-8 subfamily
- contains 1 homeobox DNA-binding domain
Compartment: nucleus
Expression:
- expressed in duodenum & pancreas (Langerhans islet beta cells & small subsets of endocrine non-beta-cells, at low levels in acinar cells)
Pathology:
- defects in PDX1 are a cause of
a) pancreatic agenesis
b) diabetes mellitus type-2
- defects in PDX1 are the cause of maturity-onset diabetes of the young type 4 (MODY4)
Related
insulin for injection (Novolin, Humulin, Lente, Semilente, Ultralente, Iletin, NPH (isophane), PZI, INS)
General
homeobox protein
Properties
SIZE: entity length = 283 aa
MW = 31 kD
COMPARTMENT: cell nucleus
MOTIF: transcriptional activation domain
SITE: 13-73
MOTIF: proline-rich region
SITE: 42-51
MOTIF: proline residue (SEVERAL)
Antp-type hexapeptide {118-123}
homeodomain
SITE: 146-205
MOTIF: nuclear translocation signal {197-203}
glycine-rich region {216-219}
proline-rich region
SITE: 239-244
MOTIF: proline residue (SEVERAL)
Database Correlations
OMIM correlations
MORBIDMAP 600733
UniProt P52945
Pfam PF00046
Entrez Gene 3651
Kegg hsa:3651
References
- UniProt :accession P52945
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/PDX1