UniProtKB - P52945 (PDX1_HUMAN)
Protein
Pancreas/duodenum homeobox protein 1
Gene
PDX1
Organism
Homo sapiens (Human)
Status
Functioni
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.
Miscellaneous
According to PubMed:16141209, it may be methylated by SETD7 in vitro. However, the relevance of methylation is unsure in vivo.
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 146 – 205 | HomeoboxPROSITE-ProRule annotationAdd BLAST | 60 |
GO - Molecular functioni
- DNA-binding transcription factor activity Source: GO_Central
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- promoter-specific chromatin binding Source: Ensembl
- protein-containing complex binding Source: Ensembl
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: GO_Central
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
- transcription factor binding Source: Ensembl
GO - Biological processi
- animal organ morphogenesis Source: ProtInc
- animal organ regeneration Source: Ensembl
- animal organ senescence Source: Ensembl
- central nervous system development Source: Ensembl
- detection of glucose Source: BHF-UCL
- digestive tract development Source: Ensembl
- endocrine pancreas development Source: GO_Central
- exocrine pancreas development Source: Ensembl
- generation of precursor metabolites and energy Source: ProtInc
- glucose homeostasis Source: Ensembl
- glucose metabolic process Source: Ensembl
- insulin secretion Source: BHF-UCL
- liver development Source: Ensembl
- morphogenesis of embryonic epithelium Source: Ensembl
- negative regulation of cell population proliferation Source: Ensembl
- negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: Ensembl
- negative regulation of transcription by RNA polymerase II Source: Ensembl
- negative regulation of type B pancreatic cell apoptotic process Source: Ensembl
- nitric oxide mediated signal transduction Source: BHF-UCL
- positive regulation of cell death Source: Ensembl
- positive regulation of cell population proliferation Source: Ensembl
- positive regulation of DNA binding Source: Ensembl
- positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: Ensembl
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- response to alkaloid Source: Ensembl
- response to chlorate Source: Ensembl
- response to cytokine Source: Ensembl
- response to drug Source: Ensembl
- response to fatty acid Source: Ensembl
- response to glucocorticoid Source: Ensembl
- response to iron(II) ion Source: Ensembl
- response to leucine Source: Ensembl
- response to nicotine Source: Ensembl
- response to vitamin Source: Ensembl
- response to wounding Source: Ensembl
- smoothened signaling pathway Source: Ensembl
- stem cell differentiation Source: Ensembl
- transcription by RNA polymerase II Source: ProtInc
- transdifferentiation Source: Ensembl
- type B pancreatic cell differentiation Source: BHF-UCL
Keywordsi
Molecular function | Activator, Developmental protein, DNA-binding |
Biological process | Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | P52945 |
Reactomei | R-HSA-210745, Regulation of gene expression in beta cells R-HSA-210747, Regulation of gene expression in early pancreatic precursor cells |
SignaLinki | P52945 |
SIGNORi | P52945 |
Names & Taxonomyi
Protein namesi | Recommended name: Pancreas/duodenum homeobox protein 1Short 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 namesi | Name:PDX1 Synonyms:IPF1, STF1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000139515.5 |
HGNCi | HGNC:6107, PDX1 |
MIMi | 600733, gene |
neXtProti | NX_P52945 |
Subcellular locationi
Cytosol
- cytosol Source: UniProtKB-SubCell
Nucleus
- nuclear chromatin Source: NTNU_SB
- nuclear speck Source: Ensembl
- nucleoplasm Source: HPA
- nucleus Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
Pancreatic agenesis 1 (PAGEN1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIMDiabetes mellitus, non-insulin-dependent (NIDDM)
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIMMaturity-onset diabetes of the young 4 (MODY4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIMKeywords - Diseasei
Diabetes mellitus, Disease mutationOrganism-specific databases
DisGeNETi | 3651 |
GeneReviewsi | PDX1 |
MalaCardsi | PDX1 |
MIMi | 125853, phenotype 260370, phenotype 606392, phenotype |
OpenTargetsi | ENSG00000139515 |
Orphaneti | 552, MODY 2805, Partial pancreatic agenesis 99885, Permanent neonatal diabetes mellitus |
PharmGKBi | PA162399173 |
Miscellaneous databases
Pharosi | P52945, Tbio |
Polymorphism and mutation databases
BioMutai | PDX1 |
DMDMi | 1708540 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000049147 | 1 – 283 | Pancreas/duodenum homeobox protein 1Add BLAST | 283 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 151 | Phosphothreonine; by PASKBy similarity | 1 | |
Modified residuei | 268 | Phosphoserine; by HIPK21 Publication | 1 |
Post-translational modificationi
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).By similarity
Keywords - PTMi
PhosphoproteinProteomic databases
jPOSTi | P52945 |
MassIVEi | P52945 |
PaxDbi | P52945 |
PeptideAtlasi | P52945 |
PRIDEi | P52945 |
ProteomicsDBi | 56554 |
PTM databases
iPTMneti | P52945 |
PhosphoSitePlusi | P52945 |
Expressioni
Tissue specificityi
Duodenum and pancreas (Langerhans islet beta cells and small subsets of endocrine non-beta-cells, at low levels in acinar cells).
Gene expression databases
Bgeei | ENSG00000139515, Expressed in duodenum and 27 other tissues |
Genevisiblei | P52945, HS |
Organism-specific databases
HPAi | ENSG00000139515, Group enriched (gallbladder, intestine, pancreas) |
Interactioni
Subunit structurei
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.
By similarity1 PublicationGO - Molecular functioni
- transcription factor binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 109860, 10 interactors |
ELMi | P52945 |
IntActi | P52945, 2 interactors |
MINTi | P52945 |
STRINGi | 9606.ENSP00000370421 |
Miscellaneous databases
RNActi | P52945, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 13 – 73 | Transactivation domainBy similarityAdd BLAST | 61 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 118 – 123 | Antp-type hexapeptide | 6 | |
Motifi | 197 – 203 | Nuclear localization signalBy similarity | 7 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 42 – 51 | Poly-Pro | 10 | |
Compositional biasi | 216 – 219 | Poly-Gly | 4 | |
Compositional biasi | 239 – 244 | Poly-Pro | 6 |
Domaini
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
Sequence similaritiesi
Keywords - Domaini
HomeoboxPhylogenomic databases
eggNOGi | KOG0489, Eukaryota |
GeneTreei | ENSGT00940000162542 |
HOGENOMi | CLU_087401_0_0_1 |
InParanoidi | P52945 |
OMAi | HTWKGQW |
OrthoDBi | 1102286at2759 |
PhylomeDBi | P52945 |
TreeFami | TF326223 |
Family and domain databases
CDDi | cd00086, homeodomain, 1 hit |
DisProti | DP01597 |
InterProi | View protein in InterPro IPR009057, Homeobox-like_sf IPR017995, Homeobox_antennapedia IPR017970, Homeobox_CS IPR001356, Homeobox_dom IPR020479, Homeobox_metazoa |
Pfami | View protein in Pfam PF00046, Homeodomain, 1 hit |
PRINTSi | PR00025, ANTENNAPEDIA PR00024, HOMEOBOX |
SMARTi | View protein in SMART SM00389, HOX, 1 hit |
SUPFAMi | SSF46689, SSF46689, 1 hit |
PROSITEi | View protein in PROSITE PS00027, HOMEOBOX_1, 1 hit PS50071, HOMEOBOX_2, 1 hit |
i Sequence
Sequence statusi: Complete.
P52945-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MNGEEQYYAA TQLYKDPCAF QRGPAPEFSA SPPACLYMGR QPPPPPPHPF
60 70 80 90 100
PGALGALEQG SPPDISPYEV PPLADDPAVA HLHHHLPAQL ALPHPPAGPF
110 120 130 140 150
PEGAEPGVLE EPNRVQLPFP WMKSTKAHAW KGQWAGGAYA AEPEENKRTR
160 170 180 190 200
TAYTRAQLLE LEKEFLFNKY ISRPRRVELA VMLNLTERHI KIWFQNRRMK
210 220 230 240 250
WKKEEDKKRG GGTAVGGGGV AEPEQDCAVT SGEELLALPP PPPPGGAVPP
260 270 280
AAPVAAREGR LPPGLSASPQ PSSVAPRRPQ EPR
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 56 | A → S in AAC05157 (PubMed:9252422).Curated | 1 | |
Sequence conflicti | 116 | Q → H in AAC05157 (PubMed:9252422).Curated | 1 | |
Sequence conflicti | 210 – 211 | GG → SS in AAC05157 (PubMed:9252422).Curated | 2 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_009309 | 18 | C → R Rare polymorphism; risk factor for type 2 diabetes. 1 PublicationCorresponds to variant dbSNP:rs137852785EnsemblClinVar. | 1 | |
Natural variantiVAR_009310 | 59 | Q → L Polymorphism; risk factor for type 2 diabetes. 1 PublicationCorresponds to variant dbSNP:rs137852784EnsemblClinVar. | 1 | |
Natural variantiVAR_009311 | 76 | D → N Polymorphism; risk factor for type 2 diabetes. 2 PublicationsCorresponds to variant dbSNP:rs137852783EnsemblClinVar. | 1 | |
Natural variantiVAR_009312 | 197 | R → H Polymorphism; risk factor for type 2 diabetes. 1 PublicationCorresponds to variant dbSNP:rs137852786EnsemblClinVar. | 1 | |
Natural variantiVAR_009313 | 243 | P → PP Polymorphism; risk factor for type 2 diabetes. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 No translation available. CH471075 Genomic DNA Translation: EAX08420.1 |
CCDSi | CCDS9327.1 |
PIRi | G01926 |
RefSeqi | NP_000200.1, NM_000209.3 |
Genome annotation databases
Ensembli | ENST00000381033; ENSP00000370421; ENSG00000139515 |
GeneIDi | 3651 |
KEGGi | hsa:3651 |
UCSCi | uc001urt.3, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 No translation available. CH471075 Genomic DNA Translation: EAX08420.1 |
CCDSi | CCDS9327.1 |
PIRi | G01926 |
RefSeqi | NP_000200.1, NM_000209.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6F8F | X-ray | 2.00 | G | 223-233 | [»] | |
BMRBi | P52945 | |||||
SMRi | P52945 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 109860, 10 interactors |
ELMi | P52945 |
IntActi | P52945, 2 interactors |
MINTi | P52945 |
STRINGi | 9606.ENSP00000370421 |
PTM databases
iPTMneti | P52945 |
PhosphoSitePlusi | P52945 |
Polymorphism and mutation databases
BioMutai | PDX1 |
DMDMi | 1708540 |
Proteomic databases
jPOSTi | P52945 |
MassIVEi | P52945 |
PaxDbi | P52945 |
PeptideAtlasi | P52945 |
PRIDEi | P52945 |
ProteomicsDBi | 56554 |
Protocols and materials databases
Antibodypediai | 22687, 849 antibodies |
DNASUi | 3651 |
Genome annotation databases
Ensembli | ENST00000381033; ENSP00000370421; ENSG00000139515 |
GeneIDi | 3651 |
KEGGi | hsa:3651 |
UCSCi | uc001urt.3, human |
Organism-specific databases
CTDi | 3651 |
DisGeNETi | 3651 |
EuPathDBi | HostDB:ENSG00000139515.5 |
GeneCardsi | PDX1 |
GeneReviewsi | PDX1 |
HGNCi | HGNC:6107, PDX1 |
HPAi | ENSG00000139515, Group enriched (gallbladder, intestine, pancreas) |
MalaCardsi | PDX1 |
MIMi | 125853, phenotype 260370, phenotype 600733, gene 606392, phenotype |
neXtProti | NX_P52945 |
OpenTargetsi | ENSG00000139515 |
Orphaneti | 552, MODY 2805, Partial pancreatic agenesis 99885, Permanent neonatal diabetes mellitus |
PharmGKBi | PA162399173 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0489, Eukaryota |
GeneTreei | ENSGT00940000162542 |
HOGENOMi | CLU_087401_0_0_1 |
InParanoidi | P52945 |
OMAi | HTWKGQW |
OrthoDBi | 1102286at2759 |
PhylomeDBi | P52945 |
TreeFami | TF326223 |
Enzyme and pathway databases
PathwayCommonsi | P52945 |
Reactomei | R-HSA-210745, Regulation of gene expression in beta cells R-HSA-210747, Regulation of gene expression in early pancreatic precursor cells |
SignaLinki | P52945 |
SIGNORi | P52945 |
Miscellaneous databases
BioGRID-ORCSi | 3651, 4 hits in 863 CRISPR screens |
ChiTaRSi | PDX1, human |
GeneWikii | PDX1 |
GenomeRNAii | 3651 |
Pharosi | P52945, Tbio |
PROi | PR:P52945 |
RNActi | P52945, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000139515, Expressed in duodenum and 27 other tissues |
Genevisiblei | P52945, HS |
Family and domain databases
CDDi | cd00086, homeodomain, 1 hit |
DisProti | DP01597 |
InterProi | View protein in InterPro IPR009057, Homeobox-like_sf IPR017995, Homeobox_antennapedia IPR017970, Homeobox_CS IPR001356, Homeobox_dom IPR020479, Homeobox_metazoa |
Pfami | View protein in Pfam PF00046, Homeodomain, 1 hit |
PRINTSi | PR00025, ANTENNAPEDIA PR00024, HOMEOBOX |
SMARTi | View protein in SMART SM00389, HOX, 1 hit |
SUPFAMi | SSF46689, SSF46689, 1 hit |
PROSITEi | View protein in PROSITE PS00027, HOMEOBOX_1, 1 hit PS50071, HOMEOBOX_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PDX1_HUMAN | |
Accessioni | P52945Primary (citable) accession number: P52945 Secondary accession number(s): O60594, Q5VYW2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | October 1, 1996 | |
Last modified: | December 2, 2020 | |
This is version 197 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- 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 - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - 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