Human Gene PKLR (ENST00000392414.7) Description and Page Index
  Description: Homo sapiens pyruvate kinase L/R (PKLR), transcript variant 2, mRNA. (from RefSeq NM_181871)
RefSeq Summary (NM_181871): 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].
Gencode Transcript: ENST00000392414.7
Gencode Gene: ENSG00000143627.19
Transcript (Including UTRs)
   Position: hg38 chr1:155,289,839-155,301,001 Size: 11,163 Total Exon Count: 11 Strand: -
Coding Region
   Position: hg38 chr1:155,290,572-155,300,887 Size: 10,316 Coding Exon Count: 11 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:155,289,839-155,301,001)mRNA (may differ from genome)Protein (543 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGIneXtProtOMIMPubMed
ReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: KPYR_HUMAN
DESCRIPTION: RecName: Full=Pyruvate kinase isozymes R/L; EC=2.7.1.40; AltName: Full=Pyruvate kinase 1; AltName: Full=R-type/L-type pyruvate kinase; AltName: Full=Red cell/liver pyruvate kinase;
FUNCTION: Plays a key role in glycolysis (By similarity).
CATALYTIC ACTIVITY: ATP + pyruvate = ADP + phosphoenolpyruvate.
COFACTOR: Magnesium.
COFACTOR: Potassium.
ENZYME REGULATION: Allosterically activated by fructose 1,6- bisphosphate.
PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D- glyceraldehyde 3-phosphate: step 5/5.
SUBUNIT: Homotetramer.
DISEASE: Defects in PKLR are the cause of pyruvate kinase hyperactivity (PKHYP) [MIM:102900]; also known as high red cell ATP syndrome. This autosomal dominant phenotype is characterized by increase of red blood cell ATP.
DISEASE: Defects in PKLR are the cause of pyruvate kinase deficiency of red cells (PKRD) [MIM:266200]. A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia.
MISCELLANEOUS: There are 4 isozymes of pyruvate kinase in mammals: L, R, M1 and M2. L type is major isozyme in the liver, R is found in red cells, M1 is the main form in muscle, heart and brain, and M2 is found in early fetal tissues.
SIMILARITY: Belongs to the pyruvate kinase family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PKLR";
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/pklr/";
WEB RESOURCE: Name=Wikipedia; Note=Pyruvate kinase entry; URL="http://en.wikipedia.org/wiki/Pyruvate_kinase";
WEB RESOURCE: Name=PKLR Mutation Database; URL="http://www.pklrmutationdatabase.com/";

-  MalaCards Disease Associations
  MalaCards Gene Search: PKLR
Diseases sorted by gene-association score: pyruvate kinase deficiency* (1705), adenosine triphosphate, elevated, of erythrocytes* (1300), hemolytic anemia (30), congenital nonspherocytic hemolytic anemia (21), gaucher's disease (14), congenital hemolytic anemia (9), neonatal jaundice (9), anhidrosis (8), maturity-onset diabetes of the young (6), hereditary spherocytosis (6), dowling-degos disease (5), dyschromatosis symmetrica hereditaria (5), malaria (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 14.55 RPKM in Liver
Total median expression: 25.43 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -36.10114-0.317 Picture PostScript Text
3' UTR -221.40733-0.302 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001697 - Pyr_Knase
IPR015813 - Pyrv/PenolPyrv_Kinase
IPR011037 - Pyrv_Knase-like_insert_dom
IPR015794 - Pyrv_Knase_a/b
IPR018209 - Pyrv_Knase_AS
IPR015793 - Pyrv_Knase_brl
IPR015795 - Pyrv_Knase_C
IPR015806 - Pyrv_Knase_insert_dom

Pfam Domains:
PF00224 - Pyruvate kinase, barrel domain
PF02887 - Pyruvate kinase, alpha/beta domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

2VGB
- X-ray MuPIT

2VGF
- X-ray MuPIT

2VGG
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
2VGI - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P30613
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0000287 magnesium ion binding
GO:0003824 catalytic activity
GO:0004743 pyruvate kinase activity
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0030955 potassium ion binding
GO:0046872 metal ion binding

Biological Process:
GO:0001666 response to hypoxia
GO:0005975 carbohydrate metabolic process
GO:0006096 glycolytic process
GO:0006754 ATP biosynthetic process
GO:0007584 response to nutrient
GO:0008152 metabolic process
GO:0009408 response to heat
GO:0009749 response to glucose
GO:0010038 response to metal ion
GO:0010226 response to lithium ion
GO:0016310 phosphorylation
GO:0032869 cellular response to insulin stimulus
GO:0033198 response to ATP
GO:0042866 pyruvate biosynthetic process
GO:0051591 response to cAMP
GO:0061621 canonical glycolysis
GO:0071872 cellular response to epinephrine stimulus

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  M15465 - Human pyruvate kinase type L mRNA, complete cds.
BC025737 - Homo sapiens pyruvate kinase, liver and RBC, mRNA (cDNA clone MGC:34243 IMAGE:5221697), complete cds.
AK225947 - Homo sapiens mRNA for pyruvate kinase, liver and RBC isoform 2 variant, clone: FCC115E04.
AB015983 - Homo sapiens mRNA for pyruvate kinase L, complete cds.
JD154712 - Sequence 135736 from Patent EP1572962.
JD259174 - Sequence 240198 from Patent EP1572962.
AK298399 - Homo sapiens cDNA FLJ51264 complete cds, highly similar to Pyruvate kinase isozymes R/L (EC 2.7.1.40).
JD121293 - Sequence 102317 from Patent EP1572962.
JD097564 - Sequence 78588 from Patent EP1572962.
JD411781 - Sequence 392805 from Patent EP1572962.
JD165824 - Sequence 146848 from Patent EP1572962.
JD403482 - Sequence 384506 from Patent EP1572962.
KJ897337 - Synthetic construct Homo sapiens clone ccsbBroadEn_06731 PKLR gene, encodes complete protein.
KJ905270 - Synthetic construct Homo sapiens clone ccsbBroadEn_14767 PKLR gene, encodes complete protein.
KR710654 - Synthetic construct Homo sapiens clone CCSBHm_00015279 PKLR (PKLR) mRNA, encodes complete protein.
KR710655 - Synthetic construct Homo sapiens clone CCSBHm_00015293 PKLR (PKLR) mRNA, encodes complete protein.
KR710656 - Synthetic construct Homo sapiens clone CCSBHm_00015374 PKLR (PKLR) mRNA, encodes complete protein.
KR710657 - Synthetic construct Homo sapiens clone CCSBHm_00015400 PKLR (PKLR) mRNA, encodes complete protein.
EU176228 - Synthetic construct Homo sapiens clone IMAGE:100006610; FLH264008.01X; RZPDo839F11245D pyruvate kinase, liver and RBC (PKLR) gene, encodes complete protein.
AB590420 - Synthetic construct DNA, clone: pFN21AE1326, Homo sapiens PKLR gene for pyruvate kinase, liver and RBC, without stop codon, in Flexi system.
JD024092 - Sequence 5116 from Patent EP1572962.
JD030063 - Sequence 11087 from Patent EP1572962.
S60712 - R-type pyruvate kinase [human, mRNA Partial Mutant, 201 nt].
CU693044 - Synthetic construct Homo sapiens gateway clone IMAGE:100023273 5' read PKLR mRNA.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00010 - Glycolysis / Gluconeogenesis
hsa00230 - Purine metabolism
hsa00620 - Pyruvate metabolism
hsa01100 - Metabolic pathways
hsa04910 - Insulin signaling pathway
hsa04930 - Type II diabetes mellitus
hsa04950 - Maturity onset diabetes of the young

BioCyc Knowledge Library
PWY66-400 - glycolysis
PWY66-407 - superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle

Reactome (by CSHL, EBI, and GO)

Protein P30613 (Reactome details) participates in the following event(s):

R-HSA-71670 phosphoenolpyruvate + ADP => pyruvate + ATP
R-HSA-163765 ChREBP activates metabolic gene expression
R-HSA-163685 Energy Metabolism
R-HSA-1430728 Metabolism
R-HSA-70171 Glycolysis
R-HSA-70326 Glucose metabolism
R-HSA-71387 Metabolism of carbohydrates
R-HSA-71670 phosphoenolpyruvate + ADP => pyruvate + ATP
R-HSA-210745 Regulation of gene expression in beta cells
R-HSA-186712 Regulation of beta-cell development
R-HSA-1266738 Developmental Biology
R-HSA-70171 Glycolysis
R-HSA-70326 Glucose metabolism
R-HSA-71387 Metabolism of carbohydrates
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: KPYR_HUMAN, NM_181871, P11973, P30613, PK1, PKL, uc001fka.1, uc001fka.2, uc001fka.3, uc001fka.4, uc001fka.5
UCSC ID: uc001fka.5
RefSeq Accession: NM_181871
Protein: P30613 (aka KPYR_HUMAN)
CCDS: CCDS44240.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.