Reviewed,
UniProtKB/Swiss-Prot P52945 (PDX1_HUMAN)
Last modified
November 25, 2008.
Version 82.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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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 |
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| 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 | |
| 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 secretionInferred from direct assay. Source: UniProtKB nitric oxide mediated signal transductionInferred from direct assay. Source: UniProtKB organ morphogenesisTraceable 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 activityTraceable author statement. Source: ProtInc transcription factor activityInferred 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
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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. |
Cross-references
Sequence databases | |
|---|---|
| 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 |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 13 Human chromosome 13: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


