PKLR

Protein identityUniProt · HPA

UniProt accession

P30613

Gene

PKLR

Ensembl

ENSG00000143627

Chromosome

1

Canonical length

574 aa

Protein class

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

Subcellular location

Cytosol

Quaternary structure

Homotetramer

OverviewNCBI Gene

The protein encoded by this gene is a pyruvate kinase that catalyzes the transphosphorylation of phohsphoenolpyruvate into pyruvate and ATP, which is the rate-limiting step of glycolysis. Defects in this enzyme, due to gene mutations or genetic variations, are the common cause of chronic hereditary nonspherocytic hemolytic anemia (CNSHA or HNSHA). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

574 residues, UniProt reviewed canonical sequence.

>P30613|PKLR
     1  MSIQENISSL QLRSWVSKSQ RDLAKSILIG APGGPAGYLR RASVAQLTQE LGTAFFQQQQ
    61  LPAAMADTFL EHLCLLDIDS EPVAARSTSI IATIGPASRS VERLKEMIKA GMNIARLNFS
   121  HGSHEYHAES IANVREAVES FAGSPLSYRP VAIALDTKGP EIRTGILQGG PESEVELVKG
   181  SQVLVTVDPA FRTRGNANTV WVDYPNIVRV VPVGGRIYID DGLISLVVQK IGPEGLVTQV
   241  ENGGVLGSRK GVNLPGAQVD LPGLSEQDVR DLRFGVEHGV DIVFASFVRK ASDVAAVRAA
   301  LGPEGHGIKI ISKIENHEGV KRFDEILEVS DGIMVARGDL GIEIPAEKVF LAQKMMIGRC
   361  NLAGKPVVCA TQMLESMITK PRPTRAETSD VANAVLDGAD CIMLSGETAK GNFPVEAVKM
   421  QHAIAREAEA AVYHRQLFEE LRRAAPLSRD PTEVTAIGAV EAAFKCCAAA IIVLTTTGRS
   481  AQLLSRYRPR AAVIAVTRSA QAARQVHLCR GVFPLLYREP PEAIWADDVD RRVQFGIESG
   541  KLRGFLRVGD LVIVVTGWRP GSGYTNIMRV LSIS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PKLR 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)

0.26

Highest tissue expression

87 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PKLR.

Disease | AllUniProt

Conditions PKLR is implicated in, by any mechanism.

• Pyruvate kinase hyperactivity (PKHYP) MIM:102900
• Anemia, congenital, non-spherocytic hemolytic, 2 (CNSHA2) MIM:266200

Disease | GeneticClinVar

115 pathogenic / likely-pathogenic of 461 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pyruvate kinase deficiency of red cells
• PKLR-related disorder
• Pyruvate kinase hyperactivity
• Congenital anemia
• Inborn genetic diseases

Disease | ImmuneIEDB

Conditions an epitope on PKLR was assayed in.

• multiple sclerosis B cell

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)

0.92

gnomAD pLI

0

gnomAD missense Z

0.98

DepMap mean gene effect

-0.2

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to epinephrine stimulus
• cellular response to insulin stimulus
• glycolytic process
• pyruvate biosynthetic process
• response to ATP
• response to cAMP
• response to glucose
• response to hypoxia
• response to metal ion
• response to nutrient

Molecular functions

• ATP binding
• kinase activity
• magnesium ion binding
• monosaccharide binding
• potassium ion binding
• pyruvate kinase activity

Cellular components

• cytoplasm
• cytosol
• extracellular exosome
• pyruvate kinase complex

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

• Allosteric enzyme
• ATP-binding
• Glycolysis
• Hereditary hemolytic anemia
• Kinase
• Magnesium
• Manganese
• Metal-binding
• Nucleotide-binding
• Phosphoprotein
• Potassium
• Pyruvate
• Transferase