PGK1

Protein identityUniProt · HPA

UniProt accession

P00558

Gene

PGK1

Ensembl

ENSG00000102144

Chromosome

X

Canonical length

417 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mid piece,Principal piece,End piece

OverviewNCBI Gene

The protein encoded by this gene is a glycolytic enzyme that catalyzes the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate. The encoded protein may also act as a cofactor for polymerase alpha. Additionally, this protein is secreted by tumor cells where it participates in angiogenesis by functioning to reduce disulfide bonds in the serine protease, plasmin, which consequently leads to the release of the tumor blood vessel inhibitor angiostatin. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Deficiency of the enzyme is associated with a wide range of clinical phenotypes hemolytic anemia and neurological impairment. Pseudogenes of this gene have been defined on chromosomes 19, 21 and the X chromosome. [provided by RefSeq, Jan 2014]

Canonical amino-acid sequenceUniProt

417 residues, UniProt reviewed canonical sequence.

>P00558|PGK1
     1  MSLSNKLTLD KLDVKGKRVV MRVDFNVPMK NNQITNNQRI KAAVPSIKFC LDNGAKSVVL
    61  MSHLGRPDGV PMPDKYSLEP VAVELKSLLG KDVLFLKDCV GPEVEKACAN PAAGSVILLE
   121  NLRFHVEEEG KGKDASGNKV KAEPAKIEAF RASLSKLGDV YVNDAFGTAH RAHSSMVGVN
   181  LPQKAGGFLM KKELNYFAKA LESPERPFLA ILGGAKVADK IQLINNMLDK VNEMIIGGGM
   241  AFTFLKVLNN MEIGTSLFDE EGAKIVKDLM SKAEKNGVKI TLPVDFVTAD KFDENAKTGQ
   301  ATVASGIPAG WMGLDCGPES SKKYAEAVTR AKQIVWNGPV GVFEWEAFAR GTKALMDEVV
   361  KATSRGCITI IGGGDTATCC AKWNTEDKVS HVSTGGGASL ELLEGKVLPG VDALSNI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PGK1 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)

0.23

Highest tissue expression

424 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PGK1.

Disease | AllUniProt

Conditions PGK1 is implicated in, by any mechanism.

• Phosphoglycerate kinase 1 deficiency (PGK1D) MIM:300653

Disease | GeneticClinVar

17 pathogenic / likely-pathogenic of 370 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Glycogen storage disease due to phosphoglycerate kinase 1 deficiency
• Inborn genetic diseases
• Male infertility due to obstructive azoospermia

Disease | ImmuneIEDB

Conditions an epitope on PGK1 was assayed in.

• melanoma T cell
• skin melanoma T cell

ReferencesPubMed · IEDB

Publications for PGK1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.47

gnomAD pLI

0.77

gnomAD missense Z

0.34

DepMap mean gene effect

-0.73

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• canonical glycolysis
• cellular response to hypoxia
• epithelial cell differentiation
• gluconeogenesis
• glycolytic process
• negative regulation of angiogenesis
• negative regulation of pyruvate decarboxylation to acetyl-CoA
• plasminogen activation

Molecular functions

• ADP binding
• ATP binding
• metal ion binding
• phosphoglycerate kinase activity
• protein serine kinase activity
• protein serine/threonine kinase activity
• protein-disulfide reductase [NAD(P)H] activity
• transmembrane transporter binding

Cellular components

• cytosol
• extracellular exosome
• extracellular space
• membrane
• membrane raft
• mitochondrial matrix

Protein domainsUniProt · Pfam · InterPro

• Phosphoglycerate kinase
• Phosphoglycerate kinase, N-terminal
• Phosphoglycerate kinase, conserved site
• Phosphoglycerate kinase superfamily
• Phosphoglycerate kinase

KeywordsUniProt

• Acetylation
• ATP-binding
• Cytoplasm
• Glycolysis
• Hereditary hemolytic anemia
• Hydroxylation
• Kinase
• Magnesium
• Metal-binding
• Mitochondrion
• Nucleotide-binding
• Phosphoprotein
• Transferase

InteractionsUniProt · HPA

Protein binding partners of PGK1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PIN1
• GAPDH
• LMNA
• PCNA
• PGK2