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
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";
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.
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.