PKLR pyruvate kinase, liver and RBC [Homo sapiens (human)] - Gene

Summary

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Official Symbol: PKLRprovided by HGNC
Official Full Name: pyruvate kinase, liver and RBCprovided by HGNC
Primary source: HGNC:9020
See related: Ensembl:ENSG00000143627; HPRD:11841; MIM:609712; Vega:OTTHUMG00000035875
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PK1; PKL; PKR; RPK; PKRL
Summary: 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]

Genomic context

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Location :: 1q21

Sequence :: Chromosome: 1; NC_000001.10 (155259084..155271225, complement)

See PKLR in Epigenomics, MapViewer

Chromosome 1 - NC_000001.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

A global geographical co-distribution between malaria and high frequency of PK deficiency seems to occur suggesting that malaria may be a selective force raising the frequency of this 277Lys variant.
Title: Pyruvate kinase deficiency in sub-Saharan Africa: identification of a highly frequent missense mutation (G829A;Glu277Lys) and association with malaria.
investigation of structure-function relationship of the N-terminus of liver pyruvate kinase and its regulation by oxidation/oxidative coupling and post-translational phosphorylation
Title: Energetic coupling between an oxidizable cysteine and the phosphorylatable N-terminus of human liver pyruvate kinase.
Rich genetic diversity was detected in PKLR, including 59 single-nucleotide polymorphisms and several loss-of-function variants (frequency 1.5%).
Title: Genetic diversity in human erythrocyte pyruvate kinase.
These results suggest that SARS coronavirus could reduce pyruvate kinase activity via its nucleocapsid protein, and this may in turn cause disease.
Title: SARS-CoV nucleocapsid protein interacts with cellular pyruvate kinase protein and inhibits its activity.
We identified the pyruvate kinase liver/red cell enzyme gene mutation of 8 children previously diagnosed with pyruvate kinase deficiency who were living in a remote town in the western United States
Title: Six children with pyruvate kinase deficiency from one small town: molecular characterization of the PK-LR gene.
The results reveal an acetylation regulation of pyruvate kinase and the link between lysine acetylation and chaperone-mediated autophagy.
Title: Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth.
Studies indicate that switching from pyruvate kinase spliced isoform PKM1 to PKM2 promotes aerobic glycolysis and provides a selective advantage for tumor formation, and the alternative splicing is controlled by hnRNP family members.
Title: Turning on a fuel switch of cancer: hnRNP proteins regulate alternative splicing of pyruvate kinase mRNA.
Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program.
Expression of pAkt, GLUT1 and TKTL1 were higher in breast cancer and DCIS than in normal tissue. Surprisingly, M2PK expression was highest in normal breast tissue.
Title: Glycolytic phenotype in breast cancer: activation of Akt, up-regulation of GLUT1, TKTL1 and down-regulation of M2PK.
These data suggest that reduced erythrocyte ATP levels may contribute to the malaria protection displayed by pyruvate kinase deficient erythrocytes in vitro.
Title: Adenosine triphosphate depletion of erythrocytes simulates the phenotype associated with pyruvate kinase deficiency and confers protection against Plasmodium falciparum in vitro.

Submit: New GeneRIF Correction See all (35)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Adenosine triphosphate, elevated, of erythrocytes

MIM: 102900

Genetic Testing Registry

NHGRI GWAS Catalog

Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P30613	Q99972	MYOC	HPRD	PubMed
BioGRID:111330	BioGRID:114847	ARHGEF6	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111330	BioGRID:130876	CLEC4G	BioGRID	PubMed	Two-hybrid
BioGRID:111330	BioGRID:108403	ESR1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111330	BioGRID:115114	KIAA0101	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111330	BioGRID:114873	KIF23	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111330	BioGRID:120738	OTUD5	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111330	BioGRID:111095	PAK1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111330	BioGRID:111142	PCNA	BioGRID	PubMed	Reconstituted Complex
BioGRID:111330	BioGRID:111787	PXN	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111330	BioGRID:132223	SUMO4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111330	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111330	BioGRID:115285	USP3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111330	BioGRID:115503	USPL1	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Adenine ribonucleotide biosynthesis, IMP => ADP,ATP, organism-specific biosystem (from KEGG)
Adenine ribonucleotide biosynthesis, IMP => ADP,ATP, organism-specific biosystemPathway module; Nucleotide and amino acid metabolism; Purine metabolism
Adenine ribonucleotide biosynthesis, IMP => ADP,ATP, conserved biosystem (from KEGG)
Adenine ribonucleotide biosynthesis, IMP => ADP,ATP, conserved biosystemPathway module; Nucleotide and amino acid metabolism; Purine metabolism
Biosynthesis of amino acids, organism-specific biosystem (from KEGG)
Biosynthesis of amino acids, organism-specific biosystem
Biosynthesis of amino acids
Biosynthesis of amino acids, conserved biosystem (from KEGG)
Biosynthesis of amino acids, conserved biosystem
Biosynthesis of amino acids
ChREBP activates metabolic gene expression, organism-specific biosystem (from REACTOME)
ChREBP activates metabolic gene expression, organism-specific biosystemChREBP (Carbohydrate Response Element Binding Protein) is a large multidomain protein containing a nuclear localization signal near its amino terminus, polyproline domains, a basic helix-loop-helix-l...
Developmental Biology, organism-specific biosystem (from REACTOME)
Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
FOXA2 and FOXA3 transcription factor networks, organism-specific biosystem (from Pathway Interaction Database)
FOXA2 and FOXA3 transcription factor networks, organism-specific biosystem
FOXA2 and FOXA3 transcription factor networks
Glucose metabolism, organism-specific biosystem (from REACTOME)
Glucose metabolism, organism-specific biosystemGlucose is the major form in which dietary sugars are made available to cells of the human body. Its breakdown is a major source of energy for all cells, and is essential for the brain and red blood ...
Glycolysis, organism-specific biosystem (from REACTOME)
Glycolysis, organism-specific biosystemThe reactions of glycolysis (e.g., van Wijk and van Solinge 2005) convert glucose 6-phosphate to pyruvate. The entire process is cytosolic. Glucose 6-phosphate is reversibly isomerized to form fructo...
Glycolysis (Embden-Meyerhof pathway), glucose => pyruvate, organism-specific biosystem (from KEGG)
Glycolysis (Embden-Meyerhof pathway), glucose => pyruvate, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Central carbohydrate metabolism
Glycolysis (Embden-Meyerhof pathway), glucose => pyruvate, conserved biosystem (from KEGG)
Glycolysis (Embden-Meyerhof pathway), glucose => pyruvate, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Central carbohydrate metabolism
Glycolysis / Gluconeogenesis, organism-specific biosystem (from KEGG)
Glycolysis / Gluconeogenesis, organism-specific biosystemGlycolysis is the process of converting glucose into pyruvate and generating small amounts of ATP (energy) and NADH (reducing power). It is a central pathway that produces important precursor metabol...
Glycolysis / Gluconeogenesis, conserved biosystem (from KEGG)
Glycolysis / Gluconeogenesis, conserved biosystemGlycolysis is the process of converting glucose into pyruvate and generating small amounts of ATP (energy) and NADH (reducing power). It is a central pathway that produces important precursor metabol...
Glycolysis and Gluconeogenesis, organism-specific biosystem (from WikiPathways)
Glycolysis and Gluconeogenesis, organism-specific biosystem
Glycolysis and Gluconeogenesis
Glycolysis, core module involving three-carbon compounds, organism-specific biosystem (from KEGG)
Glycolysis, core module involving three-carbon compounds, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Central carbohydrate metabolism
Glycolysis, core module involving three-carbon compounds, conserved biosystem (from KEGG)
Glycolysis, core module involving three-carbon compounds, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Central carbohydrate metabolism
Guanine ribonucleotide biosynthesis IMP => GDP,GTP, organism-specific biosystem (from KEGG)
Guanine ribonucleotide biosynthesis IMP => GDP,GTP, organism-specific biosystemPathway module; Nucleotide and amino acid metabolism; Purine metabolism
Guanine ribonucleotide biosynthesis IMP => GDP,GTP, conserved biosystem (from KEGG)
Guanine ribonucleotide biosynthesis IMP => GDP,GTP, conserved biosystemPathway module; Nucleotide and amino acid metabolism; Purine metabolism
Insulin signaling pathway, organism-specific biosystem (from KEGG)
Insulin signaling pathway, organism-specific biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
Insulin signaling pathway, conserved biosystem (from KEGG)
Insulin signaling pathway, conserved biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
Integration of energy metabolism, organism-specific biosystem (from REACTOME)
Integration of energy metabolism, organism-specific biosystemMany hormones that affect individual physiological processes including the regulation of appetite, absorption, transport, and oxidation of foodstuffs influence energy metabolism pathways. While insul...
Maturity onset diabetes of the young, organism-specific biosystem (from KEGG)
Maturity onset diabetes of the young, organism-specific biosystemAbout 2-5% of type II diabetic patients suffer from a monogenic disease with autosomal dominant inheritance. This monogenic form of type II diabetes is called maturity onset diabetes of the young (MO...
Maturity onset diabetes of the young, conserved biosystem (from KEGG)
Maturity onset diabetes of the young, conserved biosystemAbout 2-5% of type II diabetic patients suffer from a monogenic disease with autosomal dominant inheritance. This monogenic form of type II diabetes is called maturity onset diabetes of the young (MO...
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of carbohydrates, organism-specific biosystem (from REACTOME)
Metabolism of carbohydrates, organism-specific biosystemThese pathways together are responsible for: 1) the extraction of energy and carbon skeletons for biosyntheses from dietary sugars and related molecules; 2) the short-term storage of glucose in the b...
Purine metabolism, organism-specific biosystem (from KEGG)
Purine metabolism, organism-specific biosystem
Purine metabolism
Purine metabolism, conserved biosystem (from KEGG)
Purine metabolism, conserved biosystem
Purine metabolism
Pyruvate metabolism, organism-specific biosystem (from KEGG)
Pyruvate metabolism, organism-specific biosystem
Pyruvate metabolism
Pyruvate metabolism, conserved biosystem (from KEGG)
Pyruvate metabolism, conserved biosystem
Pyruvate metabolism
Regulation of beta-cell development, organism-specific biosystem (from REACTOME)
Regulation of beta-cell development, organism-specific biosystemThe normal development of the pancreas during gestation has been intensively investigated over the past decade especially in the mouse (Servitja and Ferrer 2004; Chakrabarti and Mirmira 2003). Studie...
Regulation of gene expression in beta cells, organism-specific biosystem (from REACTOME)
Regulation of gene expression in beta cells, organism-specific biosystemTwo transcription factors, PDX1 and HNF1A, play key roles in maintaining the gene expression pattern characteristic of mature beta cells in the endocrine pancreas. Targets of these regulatory molecul...
Type II diabetes mellitus, organism-specific biosystem (from KEGG)
Type II diabetes mellitus, organism-specific biosystemInsulin resistance is strongly associated with type II diabetes. "Diabetogenic" factors including FFA, TNFalpha and cellular stress induce insulin resistance through inhibition of IRS1 functions. Ser...
Type II diabetes mellitus, conserved biosystem (from KEGG)
Type II diabetes mellitus, conserved biosystemInsulin resistance is strongly associated with type II diabetes. "Diabetogenic" factors including FFA, TNFalpha and cellular stress induce insulin resistance through inhibition of IRS1 functions. Ser...
glycolysis, organism-specific biosystem (from BIOCYC)
glycolysis, organism-specific biosystem
glycolysis

General gene information

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Markers

RH16325 (e-PCR)
- UniSTS:31774

D1S1153 (e-PCR)
- UniSTS:149041

GDB:366638 (e-PCR)
- UniSTS:156817

D1S3522 (e-PCR)
- UniSTS:70038

RH10977 (e-PCR)
- UniSTS:7630

PKLR__7008 (e-PCR)
- UniSTS:466399

Genotypes

See PKLR SNP Geneview Report
See PKLR SNP Genotype Report
See PKLR SNP Variation Viewer Report

Homology

Homologs of the PKLR gene: The PKLR gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, zebrafish, S.cerevisiae, and A.thaliana.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
magnesium ion binding	IEA Inferred from Electronic Annotation more info
potassium ion binding	IEA Inferred from Electronic Annotation more info
pyruvate kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
ATP biosynthetic process	IEA Inferred from Electronic Annotation more info
carbohydrate metabolic process	TAS Traceable Author Statement more info
cellular response to insulin stimulus	IEA Inferred from Electronic Annotation more info
endocrine pancreas development	TAS Traceable Author Statement more info
energy reserve metabolic process	TAS Traceable Author Statement more info
glucose metabolic process	TAS Traceable Author Statement more info
glycolysis	IEA Inferred from Electronic Annotation more info
glycolysis	TAS Traceable Author Statement more info
positive regulation of cellular metabolic process	TAS Traceable Author Statement more info
pyruvate biosynthetic process	IEA Inferred from Electronic Annotation more info
response to ATP	IEA Inferred from Electronic Annotation more info
response to cAMP	IEA Inferred from Electronic Annotation more info
response to glucose stimulus	IEA Inferred from Electronic Annotation more info
response to heat	IEA Inferred from Electronic Annotation more info
response to hypoxia	IEA Inferred from Electronic Annotation more info
response to lithium ion	IEA Inferred from Electronic Annotation more info
response to nutrient	IEA Inferred from Electronic Annotation more info
response to other organism	IEA Inferred from Electronic Annotation more info
small molecule metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cytosol	TAS Traceable Author Statement more info

General protein information

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Preferred Names: pyruvate kinase isozymes R/L

Names: pyruvate kinase isozymes R/L; pyruvate kinase 1; pyruvate kinase type L; pyruvate kinase isozyme R/L; R-type/L-type pyruvate kinase; red cell/liver pyruvate kinase; pyruvate kinase, liver and blood cell

NP_000289.1

EC 2.7.1.40

NP_870986.1

EC 2.7.1.40

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011677.1 RefSeqGene

Range

5001..17142

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000298.5 → NP_000289.1 pyruvate kinase isozymes R/L isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1). Isoform 1 is also known as type R.

Source sequence(s)

AB015983, AL713999, BC025737, BF110802

Consensus CDS

CCDS1109.1

UniProtKB/Swiss-Prot

P30613

Conserved Domains (2) summary

cd00288
Location:85 – 573
Blast Score: 1797

Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...

TIGR01064
Location:86 – 570
Blast Score: 1661

pyruv_kin; pyruvate kinase
NM_181871.3 → NP_870986.1 pyruvate kinase isozymes R/L isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate 5' exon, as compared to variant 1. The resulting isoform (2) has a distinct and shorter N-terminus, as compared to isoform 1. Isoform 2 is also known as type L.

Source sequence(s)

AK225947, AL713999, BF110802, M15465

Consensus CDS

CCDS44240.1

UniProtKB/Swiss-Prot

P30613

Related

ENSP00000376214, OTTHUMP00000034069, ENST00000392414, OTTHUMT00000087408

Conserved Domains (2) summary

cd00288
Location:54 – 542
Blast Score: 1791

Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...

TIGR01064
Location:55 – 539
Blast Score: 1657

pyruv_kin; pyruvate kinase

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 PATCHES

Genomic

NW_003315906.1 Reference GRCh37.p10 PATCHES

Range

94316..106457, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000001.10 Reference GRCh37.p10 Primary Assembly

Range

155259084..155271225, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000133.1 Alternate HuRef

Range

126621396..126633527, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018912.1 Alternate CHM1_1.0

Range

161759991..161772135, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01016711.1 (28174..40305)	None
genomic	AL353760.34	None
genomic	AL713999.28 (117572..129713)	None
genomic	AMYH01001427.1 (54546..66690)	None
genomic	AY316591.1	AAP69527.1
genomic	CH471121.2	EAW53079.1
		EAW53080.1
genomic	D13243.2	BAA02515.1
genomic	S59798.1	None
genomic	S59799.1	None
genomic	S59800.1	None
genomic	S59801.1	None
genomic	S59803.1	None
genomic	S59804.1	None
genomic	S59806.1	None
genomic	S59807.1	None
genomic	S59809.1	None
genomic	S59810.1	None
genomic	S59811.1	None
genomic	S59812.1	None
genomic	S59813.1	None
genomic	S59814.1	None
genomic	S59815.1	None
genomic	S59817.1	None
genomic	S59819.1	None
genomic	S59820.1	None
genomic	S59821.1	None
genomic	S59822.1	None
genomic	S59823.1	None
genomic	S59829.1	None
genomic	S59832.1	None
genomic	U47654.1	AAA92535.1
		AAA92536.1
genomic	Z18922.1	None
mRNA	AB015983.1	BAA31706.1
mRNA	AK225947.1	None
mRNA	AK298399.1	BAG60632.1
mRNA	BC025737.1	AAH25737.1
mRNA	BF110802.1	None
mRNA	M15465.1	AAA60104.1
mRNA	S60712.1	AAB26262.1
other-genetic	EU176228.1	ABW03679.1