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Protein

Pancreas/duodenum homeobox protein 1

Gene

PDX1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.

Miscellaneous

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

Regions

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000139515.5
HGNCiHGNC:6107 PDX1
MIMi600733 gene
neXtProtiNX_P52945

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)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.
See also OMIM:606392

Keywords - Diseasei

Diabetes mellitus, Disease mutation

Organism-specific databases

DisGeNETi3651
GeneReviewsiPDX1
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, 9 interactors
ELMiP52945
IntActiP52945, 2 interactors
MINTiP52945
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

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG0489 Eukaryota
ENOG410ZTBY LUCA
GeneTreeiENSGT00910000144005
HOGENOMiHOG000115484
HOVERGENiHBG004525
InParanoidiP52945
KOiK07594
OMAiPPPCLYM
OrthoDBiEOG091G0GVH
PhylomeDBiP52945
TreeFamiTF326223

Family and domain databases

CDDicd00086 homeodomain, 1 hit
InterProiView protein in InterPro
IPR009057 Homeobox-like_sf
IPR017995 Homeobox_antennapedia
IPR017970 Homeobox_CS
IPR001356 Homeobox_dom
IPR020479 Homeobox_metazoa
PfamiView protein in Pfam
PF00046 Homeobox, 1 hit
PRINTSiPR00025 ANTENNAPEDIA
PR00024 HOMEOBOX
SMARTiView protein in SMART
SM00389 HOX, 1 hit
SUPFAMiSSF46689 SSF46689, 1 hit
PROSITEiView protein in PROSITE
PS00027 HOMEOBOX_1, 1 hit
PS50071 HOMEOBOX_2, 1 hit

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 Rare polymorphism; risk factor for type 2 diabetes. 1 PublicationCorresponds to variant dbSNP:rs137852785EnsemblClinVar.1
Natural variantiVAR_00931059Q → L Polymorphism; risk factor for type 2 diabetes. 1 PublicationCorresponds to variant dbSNP:rs137852784EnsemblClinVar.1
Natural variantiVAR_00931176D → N Polymorphism; risk factor for type 2 diabetes. 2 PublicationsCorresponds to variant dbSNP:rs137852783EnsemblClinVar.1
Natural variantiVAR_009312197R → H Polymorphism; risk factor for type 2 diabetes. 1 PublicationCorresponds to variant dbSNP:rs137852786EnsemblClinVar.1
Natural variantiVAR_009313243P → PP Polymorphism; risk factor for type 2 diabetes. 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 No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiPDX1_HUMAN
AccessioniPrimary (citable) accession number: P52945
Secondary accession number(s): O60594, Q5VYW2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: May 23, 2018
This is version 179 of the entry and version 1 of the sequence. See 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

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

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