PKM

Protein identityUniProt · HPA

UniProt accession

P14618

Gene

PKM

Ensembl

ENSG00000067225

Chromosome

15

Canonical length

531 aa

Protein class

Cancer-related genes, Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Vesicles,Cytosol,Principal piece

Quaternary structure

Homotetramer

OverviewNCBI Gene

This gene encodes a protein involved in glycolysis. The encoded protein is a pyruvate kinase that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate to ADP, generating ATP and pyruvate. This protein has been shown to interact with thyroid hormone and may mediate cellular metabolic effects induced by thyroid hormones. This protein has been found to bind Opa protein, a bacterial outer membrane protein involved in gonococcal adherence to and invasion of human cells, suggesting a role of this protein in bacterial pathogenesis. Several alternatively spliced transcript variants encoding a few distinct isoforms have been reported. [provided by RefSeq, May 2011]

Canonical amino-acid sequenceUniProt

531 residues, UniProt reviewed canonical sequence.

>P14618|PKM
     1  MSKPHSEAGT AFIQTQQLHA AMADTFLEHM CRLDIDSPPI TARNTGIICT IGPASRSVET
    61  LKEMIKSGMN VARLNFSHGT HEYHAETIKN VRTATESFAS DPILYRPVAV ALDTKGPEIR
   121  TGLIKGSGTA EVELKKGATL KITLDNAYME KCDENILWLD YKNICKVVEV GSKIYVDDGL
   181  ISLQVKQKGA DFLVTEVENG GSLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV
   241  FASFIRKASD VHEVRKVLGE KGKNIKIISK IENHEGVRRF DEILEASDGI MVARGDLGIE
   301  IPAEKVFLAQ KMMIGRCNRA GKPVICATQM LESMIKKPRP TRAEGSDVAN AVLDGADCIM
   361  LSGETAKGDY PLEAVRMQHL IAREAEAAIY HLQLFEELRR LAPITSDPTE ATAVGAVEAS
   421  FKCCSGAIIV LTKSGRSAHQ VARYRPRAPI IAVTRNPQTA RQAHLYRGIF PVLCKDPVQE
   481  AWAEDVDLRV NFAMNVGKAR GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PKM 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

3,778 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PKM.

Disease | ImmuneIEDB

Conditions an epitope on PKM was assayed in.

• multiple sclerosis B cell
• allergic disease T cell

ReferencesPubMed · IEDB

Publications for PKM 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)

0.38

gnomAD pLI

0.85

gnomAD missense Z

2.09

DepMap mean gene effect

-0.75

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 insulin stimulus
• glycolytic process
• positive regulation of cytoplasmic translation
• positive regulation of sprouting angiogenesis
• positive regulation of transcription by RNA polymerase II
• programmed cell death

Molecular functions

• ATP binding
• cadherin binding
• histone H3T11 kinase activity
• magnesium ion binding
• MHC class II protein complex binding
• mRNA binding
• non-membrane spanning protein tyrosine kinase activity
• potassium ion binding
• protein homodimerization activity
• protein serine/threonine kinase activity
• protein tyrosine kinase activity
• pyruvate kinase activity
• RNA binding
• transcription coactivator activity

Cellular components

• cytoplasm
• cytosol
• extracellular exosome
• extracellular region
• extracellular vesicle
• ficolin-1-rich granule lumen
• mitochondrion
• nucleoplasm
• nucleus
• rough endoplasmic reticulum
• secretory granule lumen
• sperm principal piece
• vesicle

Protein domainsUniProt · Pfam · InterPro

• Pyruvate kinase
• Pyruvate kinase-like, insert domain superfamily
• Pyruvate kinase, barrel
• Pyruvate kinase, C-terminal
• Pyruvate kinase, insert domain superfamily
• Pyruvate/Phosphoenolpyruvate kinase-like domain superfamily
• Pyruvate kinase, active site
• Pyruvate kinase, C-terminal domain superfamily
• Pyruvate kinase-like domain superfamily
• Pyruvate kinase, barrel domain
• Pyruvate kinase, alpha/beta domain

KeywordsUniProt

• Acetylation
• Allosteric enzyme
• ATP-binding
• Cytoplasm
• Glycolysis
• Hydroxylation
• Isopeptide bond
• Kinase
• Magnesium
• Metal-binding
• Methylation
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Potassium
• Pyruvate
• S-nitrosylation
• Transferase
• Translation regulation
• Ubl conjugation

InteractionsUniProt · HPA

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

• EGLN3
• HERC1
• HIF1A
• JMJD8
• PML
• POU5F1
• TRAF4
• TRIM35
• TSC22D2
• PANK4
• ARRB1
• ARRB2
• CTNNB1