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Protein

Pancreas/duodenum homeobox protein 1

Gene

PDX1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi146 – 205HomeoboxPROSITE-ProRule annotationAdd BLAST60

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000139515-MONOMER.
ReactomeiR-HSA-210745. Regulation of gene expression in beta cells.
R-HSA-210747. Regulation of gene expression in early pancreatic precursor cells.
SignaLinkiP52945.
SIGNORiP52945.

Names & Taxonomyi

Protein namesi
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 namesi
Name:PDX1
Synonyms:IPF1, STF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:6107. PDX1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & 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.
See also OMIM:260370
Diabetes 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.
See also OMIM:125853
Maturity-onset diabetes of the young 4 (MODY4)2 Publications
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.
See also OMIM:606392
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00930918C → R in MODY4. 1 PublicationCorresponds to variant rs137852785dbSNPEnsembl.1
Natural variantiVAR_00931059Q → L in MODY4. 1 PublicationCorresponds to variant rs137852784dbSNPEnsembl.1
Natural variantiVAR_00931176D → N in MODY4; unknown pathological significance. 2 PublicationsCorresponds to variant rs137852783dbSNPEnsembl.1
Natural variantiVAR_009312197R → H in MODY4. 1 PublicationCorresponds to variant rs137852786dbSNPEnsembl.1
Natural variantiVAR_009313243P → PP in MODY4. 1 Publication1

Keywords - Diseasei

Diabetes mellitus, Disease mutation

Organism-specific databases

DisGeNETi3651.
MalaCardsiPDX1.
MIMi125853. phenotype.
260370. phenotype.
606392. phenotype.
OpenTargetsiENSG00000139515.
Orphaneti552. MODY.
2805. Partial pancreatic agenesis.
99885. Permanent neonatal diabetes mellitus.
PharmGKBiPA162399173.

Polymorphism and mutation databases

BioMutaiPDX1.
DMDMi1708540.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000491471 – 283Pancreas/duodenum homeobox protein 1Add BLAST283

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei151Phosphothreonine; by PASKBy similarity1
Modified residuei268Phosphoserine; by HIPK21 Publication1

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

Phosphoprotein

Proteomic databases

PaxDbiP52945.
PeptideAtlasiP52945.
PRIDEiP52945.

PTM databases

iPTMnetiP52945.
PhosphoSitePlusiP52945.

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

BgeeiENSG00000139515.
CleanExiHS_PDX1.
GenevisibleiP52945. HS.

Organism-specific databases

HPAiCAB025873.
HPA059146.

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 Publication

Protein-protein interaction databases

BioGridi109860. 10 interactors.
IntActiP52945. 2 interactors.
MINTiMINT-1894661.
STRINGi9606.ENSP00000370421.

Structurei

3D structure databases

ProteinModelPortaliP52945.
SMRiP52945.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni13 – 73Transactivation domainBy similarityAdd BLAST61

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi118 – 123Antp-type hexapeptide6
Motifi197 – 203Nuclear localization signalBy similarity7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi42 – 51Poly-Pro10
Compositional biasi216 – 219Poly-Gly4
Compositional biasi239 – 244Poly-Pro6

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

Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG0489. Eukaryota.
ENOG410ZTBY. LUCA.
GeneTreeiENSGT00760000118940.
HOGENOMiHOG000115484.
HOVERGENiHBG004525.
InParanoidiP52945.
KOiK07594.
OMAiPPPCLYM.
OrthoDBiEOG091G0GVH.
PhylomeDBiP52945.
TreeFamiTF326223.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017995. Homeobox_antennapedia.
IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSiPR00025. ANTENNAPEDIA.
PR00024. HOMEOBOX.
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P52945-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:283
Mass (Da):30,771
Last modified:October 1, 1996 - v1
Checksum:i5D48EC8D3289F72B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti56A → S in AAC05157 (PubMed:9252422).Curated1
Sequence conflicti116Q → H in AAC05157 (PubMed:9252422).Curated1
Sequence conflicti210 – 211GG → SS in AAC05157 (PubMed:9252422).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00930918C → R in MODY4. 1 PublicationCorresponds to variant rs137852785dbSNPEnsembl.1
Natural variantiVAR_00931059Q → L in MODY4. 1 PublicationCorresponds to variant rs137852784dbSNPEnsembl.1
Natural variantiVAR_00931176D → N in MODY4; unknown pathological significance. 2 PublicationsCorresponds to variant rs137852783dbSNPEnsembl.1
Natural variantiVAR_009312197R → H in MODY4. 1 PublicationCorresponds to variant rs137852786dbSNPEnsembl.1
Natural variantiVAR_009313243P → PP in MODY4. 1 Publication1

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. Translation: CAH72544.1.
CH471075 Genomic DNA. Translation: EAX08420.1.
CCDSiCCDS9327.1.
PIRiG01926.
RefSeqiNP_000200.1. NM_000209.3.
UniGeneiHs.32938.

Genome annotation databases

EnsembliENST00000381033; ENSP00000370421; ENSG00000139515.
GeneIDi3651.
KEGGihsa:3651.
UCSCiuc001urt.3. human.

Keywords - Coding sequence diversityi

Polymorphism

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. Translation: CAH72544.1.
CH471075 Genomic DNA. Translation: EAX08420.1.
CCDSiCCDS9327.1.
PIRiG01926.
RefSeqiNP_000200.1. NM_000209.3.
UniGeneiHs.32938.

3D structure databases

ProteinModelPortaliP52945.
SMRiP52945.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109860. 10 interactors.
IntActiP52945. 2 interactors.
MINTiMINT-1894661.
STRINGi9606.ENSP00000370421.

PTM databases

iPTMnetiP52945.
PhosphoSitePlusiP52945.

Polymorphism and mutation databases

BioMutaiPDX1.
DMDMi1708540.

Proteomic databases

PaxDbiP52945.
PeptideAtlasiP52945.
PRIDEiP52945.

Protocols and materials databases

DNASUi3651.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000381033; ENSP00000370421; ENSG00000139515.
GeneIDi3651.
KEGGihsa:3651.
UCSCiuc001urt.3. human.

Organism-specific databases

CTDi3651.
DisGeNETi3651.
GeneCardsiPDX1.
GeneReviewsiPDX1.
HGNCiHGNC:6107. PDX1.
HPAiCAB025873.
HPA059146.
MalaCardsiPDX1.
MIMi125853. phenotype.
260370. phenotype.
600733. gene.
606392. phenotype.
neXtProtiNX_P52945.
OpenTargetsiENSG00000139515.
Orphaneti552. MODY.
2805. Partial pancreatic agenesis.
99885. Permanent neonatal diabetes mellitus.
PharmGKBiPA162399173.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0489. Eukaryota.
ENOG410ZTBY. LUCA.
GeneTreeiENSGT00760000118940.
HOGENOMiHOG000115484.
HOVERGENiHBG004525.
InParanoidiP52945.
KOiK07594.
OMAiPPPCLYM.
OrthoDBiEOG091G0GVH.
PhylomeDBiP52945.
TreeFamiTF326223.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000139515-MONOMER.
ReactomeiR-HSA-210745. Regulation of gene expression in beta cells.
R-HSA-210747. Regulation of gene expression in early pancreatic precursor cells.
SignaLinkiP52945.
SIGNORiP52945.

Miscellaneous databases

GeneWikiiPDX1.
GenomeRNAii3651.
PROiP52945.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000139515.
CleanExiHS_PDX1.
GenevisibleiP52945. HS.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017995. Homeobox_antennapedia.
IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSiPR00025. ANTENNAPEDIA.
PR00024. HOMEOBOX.
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPDX1_HUMAN
AccessioniPrimary (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: November 2, 2016
This is version 166 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Miscellaneous

According to PubMed:16141209, it may be methylated by SETD7 in vitro. However, the relevance of methylation is unsure in vivo.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.