Human Gene PKM (ENST00000319622.10) from GENCODE V44
  Description: Homo sapiens pyruvate kinase M1/2 (PKM), transcript variant 3, mRNA. (from RefSeq NM_182471)
RefSeq Summary (NM_182470): 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].
Gencode Transcript: ENST00000319622.10
Gencode Gene: ENSG00000067225.21
Transcript (Including UTRs)
   Position: hg38 chr15:72,199,029-72,231,386 Size: 32,358 Total Exon Count: 11 Strand: -
Coding Region
   Position: hg38 chr15:72,199,650-72,219,097 Size: 19,448 Coding Exon Count: 10 

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RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr15:72,199,029-72,231,386)mRNA (may differ from genome)Protein (531 aa)
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-  Comments and Description Text from UniProtKB
  ID: KPYM_HUMAN
DESCRIPTION: RecName: Full=Pyruvate kinase isozymes M1/M2; EC=2.7.1.40; AltName: Full=Cytosolic thyroid hormone-binding protein; Short=CTHBP; AltName: Full=Opa-interacting protein 3; Short=OIP-3; AltName: Full=Pyruvate kinase 2/3; AltName: Full=Pyruvate kinase muscle isozyme; AltName: Full=Thyroid hormone-binding protein 1; Short=THBP1; AltName: Full=Tumor M2-PK; AltName: Full=p58;
FUNCTION: Glycolytic enzyme that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. Stimulates POU5F1-mediated transcriptional activation. Plays a general role in caspase independent cell death of tumor cells. The ratio betwween the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production. The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival.
CATALYTIC ACTIVITY: ATP + pyruvate = ADP + phosphoenolpyruvate.
COFACTOR: Magnesium.
COFACTOR: Potassium.
ENZYME REGULATION: Isoform M2 is allosterically activated by D- fructose 1,6-bisphosphate (FBP). Inhibited by oxalate and 3,3',5- triiodo-L-thyronine (T3). The activity of the tetrameric form is inhibited by PML. Selective binding to tyrosine-phosphorylated peptides releases the allosteric activator FBP, leading to inhibition of PKM enzymatic activity, this diverts glucose metabolites from energy production to anabolic processes when cells are stimulated by certain growth factors.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=2.7 mM for phosphoenolpyruvate (at 32 degrees Celsius, pH 8.0); KM=0.17 mM for phosphoenolpyruvate (in the presence of 2mM FBP, at 32 degrees Celsius, pH 8.0); KM=0.34 mM for ADP (at 32 degrees Celsius, pH 8.0); KM=0.24 mM for ADP (in the presence of 2mM FBP, at 32 degrees Celsius, pH 8.0); KM=0.13 mM for phosphoenolpyruvate (in the presence of 2mM FBP, at 25 degrees Celsius); KM=0.63 mM for ADP (in the presence of 2mM FBP, at 25 degrees Celsius); pH dependence: Optimum pH for T3 binding is 6.0-6.5. Increase in pH causes T3 binding to drop, does not bind T3 above pH 9.0 or below pH 5.0;
PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D- glyceraldehyde 3-phosphate: step 5/5.
SUBUNIT: Monomer and homotetramer. Exists as a monomer in the absence of FBP, and reversibly associates to form a homotetramer in the presence of FBP. The monomeric form binds T3. Tetramer formation induces pyruvate kinase activity. The tetrameric form has high affinity for the substrate and is associated within the glycolytic enzyme complex. Exists in a nearly inactive dimeric form in tumor cells and the dimeric form has less affinity for the substrate. Binding to certain oncoproteins such as HPV-16 E7 oncoprotein can trigger dimerization. FBP stimulates the formation of tetramers from dimers. Interacts with HERC1, POU5F1 and PML. Interacts (isoform M2) with EGLN3; the interaction hydroxylates PKM under hypoxia and enhances binding to HIF1A. Interacts (isoform M2) with HIF1A; the interaction is enhanced by binding of EGLN3, promoting enhanced transcription activity under hypoxia.
INTERACTION: P49407:ARRB1; NbExp=3; IntAct=EBI-353408, EBI-743313; P32121:ARRB2; NbExp=4; IntAct=EBI-353408, EBI-714559; Q9H6Z9:EGLN3; NbExp=2; IntAct=EBI-4304679, EBI-1175354; Q16665:HIF1A; NbExp=7; IntAct=EBI-4304679, EBI-447269; P04049:RAF1; NbExp=3; IntAct=EBI-353408, EBI-365996;
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocates to the nucleus in response to different apoptotic stimuli. Nuclear translocation is sufficient to induce cell death that is caspase independent, isoform-specific and independent of its enzymatic activity.
TISSUE SPECIFICITY: Specifically expressed in proliferating cells, such as embryonic stem cells, embryonic carcinoma cells, as well as cancer cells.
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
PTM: ISGylated.
PTM: Under hypoxia, hydroxylated by EGLN3.
MISCELLANEOUS: There are 4 isozymes of pyruvate kinase in mammals (L, R, M1, M2) encoded by 2 different genes: PKLR and PKM. The L and R isozymes are generated from the PKLR by differential splicing of RNA; the M1 and M2 forms are produced from the PKM gene by differential splicing. 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 as well as in most cancer cells.
SIMILARITY: Belongs to the pyruvate kinase family.
SEQUENCE CAUTION: Sequence=BAG57589.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PKM2ID41728ch15q22.html";
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/pkm2/";
WEB RESOURCE: Name=Wikipedia; Note=Pyruvate kinase entry; URL="http://en.wikipedia.org/wiki/Pyruvate_kinase";

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: PKM
Diseases sorted by gene-association score: pyruvate kinase deficiency (15), acute diarrhea (8), pigmentation disease (7), atrichia with papular lesions (7), linitis plastica (7), gastric diffuse adenocarcinoma (6), kernicterus (6), li-fraumeni syndrome (5), bilirubin metabolic disorder (4), colorectal cancer (1)

-  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: 664.82 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 8863.57 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 -249.20500-0.498 Picture PostScript Text
3' UTR -199.90621-0.322 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
1T5A - X-ray MuPIT 1ZJH - X-ray MuPIT 3BJF - X-ray 3BJT - X-ray 3G2G - X-ray MuPIT 3GQY - X-ray MuPIT 3GR4 - X-ray MuPIT 3H6O - X-ray MuPIT 3ME3 - X-ray MuPIT 3SRD - X-ray MuPIT 3SRF - X-ray MuPIT 3SRH - X-ray MuPIT 3U2Z - X-ray MuPIT 4B2D - X-ray MuPIT 4G1N - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P14618
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-  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:0003723 RNA binding
GO:0003824 catalytic activity
GO:0004743 pyruvate kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0023026 MHC class II protein complex binding
GO:0030955 potassium ion binding
GO:0042802 identical protein binding
GO:0043531 ADP binding
GO:0045296 cadherin binding
GO:0046872 metal ion binding
GO:0070324 thyroid hormone binding

Biological Process:
GO:0001666 response to hypoxia
GO:0001889 liver development
GO:0006006 glucose metabolic process
GO:0006096 glycolytic process
GO:0006754 ATP biosynthetic process
GO:0007584 response to nutrient
GO:0008152 metabolic process
GO:0009629 response to gravity
GO:0010033 response to organic substance
GO:0012501 programmed cell death
GO:0014870 response to muscle inactivity
GO:0016310 phosphorylation
GO:0031100 animal organ regeneration
GO:0032868 response to insulin
GO:0032869 cellular response to insulin stimulus
GO:0042866 pyruvate biosynthetic process
GO:0043312 neutrophil degranulation
GO:0043403 skeletal muscle tissue regeneration
GO:0051289 protein homotetramerization
GO:0061621 canonical glycolysis

Cellular Component:
GO:0001917 photoreceptor inner segment
GO:0005576 extracellular region
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005829 cytosol
GO:0005929 cilium
GO:0031012 extracellular matrix
GO:0031982 vesicle
GO:0034774 secretory granule lumen
GO:0043209 myelin sheath
GO:0070062 extracellular exosome
GO:1902912 pyruvate kinase complex
GO:1903561 extracellular vesicle
GO:1904813 ficolin-1-rich granule lumen


-  Descriptions from all associated GenBank mRNAs
  BC035198 - Homo sapiens pyruvate kinase, muscle, mRNA (cDNA clone MGC:9369 IMAGE:3859987), complete cds.
M26252 - Human TCB gene encoding cytosolic thyroid hormone-binding protein, complete cds.
EU794631 - Homo sapiens epididymis secretory protein Li 30 (HEL-S-30) mRNA, complete cds.
HZ489613 - JP 2016020328-A/13: ANTICANCER AGENT.
LX088621 - JP 2017075124-A/1: DRUG SENSITIVITY ENHANCING AGENT FOR CANCER CELL, METHOD FOR PREDICTING DRUG SENSITIVITY, AND DRUG SENSITIVITY BIOMARKER.
BC023592 - Homo sapiens pyruvate kinase, muscle, mRNA (cDNA clone IMAGE:4646848).
BC096823 - Homo sapiens pyruvate kinase, muscle, mRNA (cDNA clone IMAGE:30558692).
BC007640 - Homo sapiens pyruvate kinase, muscle, mRNA (cDNA clone MGC:15908 IMAGE:3533876), complete cds.
BC012811 - Homo sapiens pyruvate kinase, muscle, mRNA (cDNA clone MGC:3932 IMAGE:2958817), complete cds.
BC000481 - Homo sapiens pyruvate kinase, muscle, mRNA (cDNA clone MGC:8698 IMAGE:2964687), complete cds.
BC094767 - Homo sapiens pyruvate kinase, muscle, mRNA (cDNA clone MGC:104654 IMAGE:5296639), complete cds.
AK092369 - Homo sapiens cDNA FLJ35050 fis, clone OCBBF2018167, highly similar to Pyruvate kinase isozyme M1 (EC 2.7.1.40).
AK299413 - Homo sapiens cDNA FLJ53645 complete cds, highly similar to Pyruvate kinase isozyme M1 (EC 2.7.1.40).
BC007952 - Homo sapiens pyruvate kinase, muscle, mRNA (cDNA clone MGC:14360 IMAGE:4299213), complete cds.
AK297951 - Homo sapiens cDNA FLJ53368 complete cds, highly similar to Pyruvate kinase isozymes M1/M2 (EC 2.7.1.40).
M23725 - Human M2-type pyruvate kinase mRNA, complete cds.
AK222927 - Homo sapiens mRNA for pyruvate kinase 3 isoform 1 variant, clone: HRC08174.
AK300800 - Homo sapiens cDNA FLJ54554 complete cds, highly similar to Pyruvate kinase isozymes M1/M2 (EC 2.7.1.40).
AK307855 - Homo sapiens cDNA, FLJ97803.
AK294315 - Homo sapiens cDNA FLJ56065 complete cds, highly similar to Pyruvate kinase isozyme M1 (EC 2.7.1.40).
AK309781 - Homo sapiens cDNA, FLJ99822.
AK312253 - Homo sapiens cDNA, FLJ92548, highly similar to Homo sapiens pyruvate kinase, muscle (PKM2), mRNA.
AK308264 - Homo sapiens cDNA, FLJ98212.
Z36831 - H.sapiens (xs25) mRNA, 443bp.
BC035487 - Homo sapiens pyruvate kinase, muscle, mRNA (cDNA clone IMAGE:4779421), with apparent retained intron.
BC051346 - Homo sapiens cDNA clone IMAGE:6461886, **** WARNING: chimeric clone ****.
AF025439 - Homo sapiens Opa-interacting protein OIP3 mRNA, partial cds.
BC019265 - Homo sapiens pyruvate kinase, muscle, mRNA (cDNA clone IMAGE:3503708), partial cds.
BC023328 - Homo sapiens pyruvate kinase, muscle, mRNA (cDNA clone IMAGE:4510296).
BX648597 - Homo sapiens mRNA; cDNA DKFZp686G12209 (from clone DKFZp686G12209).
JD253237 - Sequence 234261 from Patent EP1572962.
JD554754 - Sequence 535778 from Patent EP1572962.
JD120305 - Sequence 101329 from Patent EP1572962.
JD360415 - Sequence 341439 from Patent EP1572962.
JD067018 - Sequence 48042 from Patent EP1572962.
JD186650 - Sequence 167674 from Patent EP1572962.
JD227184 - Sequence 208208 from Patent EP1572962.
JD323231 - Sequence 304255 from Patent EP1572962.
JD385499 - Sequence 366523 from Patent EP1572962.
JD174331 - Sequence 155355 from Patent EP1572962.
JD024294 - Sequence 5318 from Patent EP1572962.
JD030195 - Sequence 11219 from Patent EP1572962.
JD026312 - Sequence 7336 from Patent EP1572962.
JD403809 - Sequence 384833 from Patent EP1572962.
JD021887 - Sequence 2911 from Patent EP1572962.
JD029525 - Sequence 10549 from Patent EP1572962.
JD391000 - Sequence 372024 from Patent EP1572962.
JD540550 - Sequence 521574 from Patent EP1572962.
JD540025 - Sequence 521049 from Patent EP1572962.
JD042742 - Sequence 23766 from Patent EP1572962.
JD047097 - Sequence 28121 from Patent EP1572962.
JD326238 - Sequence 307262 from Patent EP1572962.
JD131573 - Sequence 112597 from Patent EP1572962.
JD369818 - Sequence 350842 from Patent EP1572962.
JD561983 - Sequence 543007 from Patent EP1572962.
JD144965 - Sequence 125989 from Patent EP1572962.
EU832358 - Synthetic construct Homo sapiens clone HAIB:100067387; DKFZo008H1227 pyruvate kinase, muscle protein (PKM2) gene, encodes complete protein.
KJ891817 - Synthetic construct Homo sapiens clone ccsbBroadEn_01211 PKM2 gene, encodes complete protein.
KJ905271 - Synthetic construct Homo sapiens clone ccsbBroadEn_14768 PKM2 gene, encodes complete protein.
KR710112 - Synthetic construct Homo sapiens clone CCSBHm_00009784 PKM (PKM) mRNA, encodes complete protein.
KR710113 - Synthetic construct Homo sapiens clone CCSBHm_00009785 PKM (PKM) mRNA, encodes complete protein.
EU832443 - Synthetic construct Homo sapiens clone HAIB:100067472; DKFZo004H1228 pyruvate kinase, muscle protein (PKM2) gene, encodes complete protein.
DQ892739 - Synthetic construct clone IMAGE:100005369; FLH189257.01X; RZPDo839D0374D pyruvate kinase, muscle (PKM2) gene, encodes complete protein.
EU176742 - Synthetic construct Homo sapiens clone IMAGE:100011510; FLH189256.01L; RZPDo839G10255D pyruvate kinase, muscle (PKM2) gene, encodes complete protein.
AB528306 - Synthetic construct DNA, clone: pF1KB9947, Homo sapiens PKM2 gene for pyruvate kinase, muscle, without stop codon, in Flexi system.
HZ473969 - WO 2016002844-A/83: ANTI-INVASIVE/ANTI-METASTATIC DRUG FOR PANCREATIC CANCER CELL.
JD019461 - Sequence 485 from Patent EP1572962.
JD035609 - Sequence 16633 from Patent EP1572962.
Z36786 - H.sapiens (xs130) mRNA, 260bp.
HZ473968 - WO 2016002844-A/82: ANTI-INVASIVE/ANTI-METASTATIC DRUG FOR PANCREATIC CANCER CELL.
JD024738 - Sequence 5762 from Patent EP1572962.
JD033454 - Sequence 14478 from Patent EP1572962.
JD027287 - Sequence 8311 from Patent EP1572962.
JD031777 - Sequence 12801 from Patent EP1572962.
HZ473970 - WO 2016002844-A/84: ANTI-INVASIVE/ANTI-METASTATIC DRUG FOR PANCREATIC CANCER CELL.
HZ473967 - WO 2016002844-A/81: ANTI-INVASIVE/ANTI-METASTATIC DRUG FOR PANCREATIC CANCER CELL.
JD027499 - Sequence 8523 from Patent EP1572962.
JD031362 - Sequence 12386 from Patent EP1572962.
LF208528 - JP 2014500723-A/16031: Polycomb-Associated Non-Coding RNAs.
MA444105 - JP 2018138019-A/16031: Polycomb-Associated Non-Coding RNAs.
LF377353 - JP 2014500723-A/184856: Polycomb-Associated Non-Coding RNAs.
MA612930 - JP 2018138019-A/184856: Polycomb-Associated Non-Coding RNAs.
LF377352 - JP 2014500723-A/184855: Polycomb-Associated Non-Coding RNAs.
MA612929 - JP 2018138019-A/184855: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00010 - Glycolysis / Gluconeogenesis
hsa00230 - Purine metabolism
hsa00620 - Pyruvate metabolism
hsa01100 - Metabolic pathways
hsa04930 - Type II diabetes mellitus

Reactome (by CSHL, EBI, and GO)

Protein P14618 (Reactome details) participates in the following event(s):

R-HSA-6800434 Exocytosis of ficolin-rich granule lumen proteins
R-HSA-6798748 Exocytosis of secretory granule lumen proteins
R-HSA-6798695 Neutrophil degranulation
R-HSA-168249 Innate Immune System
R-HSA-168256 Immune System
R-HSA-71670 phosphoenolpyruvate + ADP => pyruvate + ATP
R-HSA-70171 Glycolysis
R-HSA-70326 Glucose metabolism
R-HSA-71387 Metabolism of carbohydrates
R-HSA-1430728 Metabolism
R-HSA-71670 phosphoenolpyruvate + ADP => pyruvate + ATP
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: A6NFK3, B2R5N8, B3KRY0, B4DFX8, B4DUU6, ENST00000319622.1, ENST00000319622.2, ENST00000319622.3, ENST00000319622.4, ENST00000319622.5, ENST00000319622.6, ENST00000319622.7, ENST00000319622.8, ENST00000319622.9, KPYM_HUMAN, NM_182471, OIP3, P14618, P14786, PK2, PK3, PKM2, Q53GK4, Q96E76, Q9BWB5, Q9UCV6, Q9UPF2, uc002atw.1, uc002atw.2
UCSC ID: ENST00000319622.10
RefSeq Accession: NM_182470
Protein: P14618 (aka KPYM_HUMAN)
CCDS: CCDS32285.1

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