PDX1

Protein identityUniProt · HPA

UniProt accession

P52945

Gene

PDX1

Ensembl

ENSG00000139515

Chromosome

13

Canonical length

283 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm

OverviewNCBI Gene

The protein encoded by this gene is a transcriptional activator of several genes, including insulin, somatostatin, glucokinase, islet amyloid polypeptide, and glucose transporter type 2. The encoded nuclear protein is involved in the early development of the pancreas and plays a major role in glucose-dependent regulation of insulin gene expression. Defects in this gene are a cause of pancreatic agenesis, which can lead to early-onset insulin-dependent diabetes mellitus (IDDM), as well as maturity onset diabetes of the young type 4 (MODY4). [provided by RefSeq, Aug 2017]

Canonical amino-acid sequenceUniProt

283 residues, UniProt reviewed canonical sequence.

>P52945|PDX1
     1  MNGEEQYYAA TQLYKDPCAF QRGPAPEFSA SPPACLYMGR QPPPPPPHPF PGALGALEQG
    61  SPPDISPYEV PPLADDPAVA HLHHHLPAQL ALPHPPAGPF PEGAEPGVLE EPNRVQLPFP
   121  WMKSTKAHAW KGQWAGGAYA AEPEENKRTR TAYTRAQLLE LEKEFLFNKY ISRPRRVELA
   181  VMLNLTERHI KIWFQNRRMK WKKEEDKKRG GGTAVGGGGV AEPEQDCAVT SGEELLALPP
   241  PPPPGGAVPP AAPVAAREGR LPPGLSASPQ PSSVAPRRPQ EPR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PDX1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.65

Highest tissue expression

39 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PDX1.

Disease | AllUniProt

Conditions PDX1 is implicated in, by any mechanism.

• Pancreatic agenesis 1 (PAGEN1) MIM:260370
• Type 2 diabetes mellitus (T2D) MIM:125853
• Maturity-onset diabetes of the young 4 (MODY4) MIM:606392

Disease | GeneticClinVar

15 pathogenic / likely-pathogenic of 265 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pancreatic agenesis 1
• Maturity-onset diabetes of the young type 4
• PDX1-related disorder
• Diabetes mellitus type 2, susceptibility to
• Permanent neonatal diabetes mellitus

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.05

gnomAD pLI

0.02

gnomAD missense Z

-0.27

DepMap mean gene effect

0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• animal organ morphogenesis
• animal organ regeneration
• digestive tract development
• exocrine pancreas development
• generation of precursor metabolites and energy
• glucose mediated signaling pathway
• glucose metabolic process
• insulin secretion
• intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
• liver development
• morphogenesis of embryonic epithelium
• negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
• negative regulation of epithelial cell proliferation
• negative regulation of transcription by RNA polymerase II
• negative regulation of type B pancreatic cell apoptotic process
• positive regulation of insulin secretion
• positive regulation of insulin secretion involved in cellular response to glucose stimulus
• positive regulation of transcription by RNA polymerase II
• positive regulation of type B pancreatic cell proliferation
• regulation of transcription by RNA polymerase II
• response to alkaloid
• response to chlorate
• response to cytokine
• response to fatty acid
• response to glucocorticoid
• response to iron(II) ion
• response to L-leucine
• response to nicotine
• response to vitamin
• response to xenobiotic stimulus
• smoothened signaling pathway
• stem cell differentiation
• transcription by RNA polymerase II
• transdifferentiation
• type B pancreatic cell apoptotic process
• type B pancreatic cell differentiation
• type B pancreatic cell proliferation
• cellular response to acadesine

Molecular functions

• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity
• DNA-binding transcription factor activity, RNA polymerase II-specific
• promoter-specific chromatin binding
• protein-containing complex binding
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• RNA polymerase II-specific DNA-binding transcription factor binding
• sequence-specific double-stranded DNA binding

Cellular components

• chromatin
• cytosol
• nuclear speck
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Homeodomain
• Homedomain-like superfamily
• Homeobox, conserved site
• Homeobox protein, antennapedia type
• Homeodomain, metazoa
• Homeodomain

KeywordsUniProt

• Activator
• Cytoplasm
• Developmental protein
• Diabetes mellitus
• DNA-binding
• Homeobox
• Nucleus
• Phosphoprotein
• Transcription
• Transcription regulation

InteractionsUniProt · HPA

Protein binding partners of PDX1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SPOP
• MAFA