P52480
SS
Gene name |
Pkm (Pk3, Pkm2, Pykm) |
Protein name |
Pyruvate kinase PKM |
Names |
EC 2.7.1.40 , Pyruvate kinase muscle isozyme , Threonine-protein kinase PKM2 , EC 2.7.11.1 , Tyrosine-protein kinase PKM2 , EC 2.7.10.2 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:18746 |
EC number |
2.7.1.40: Phosphotransferases with an alcohol group as acceptor |
Protein Class |
|
Descriptions
Pyruvate kinase M2 (PKM2) plays a vital role in glycolysis, and it catalyzes the conversion of phosphoenolpyruvate to pyruvate with the production of ATP in the final reaction of glycolysis. PKM2 provides an in vivo growth advantage in cancer cells. Pyruvate Kinase isozymes type PKM1, PKL, and PKR exist in unstable and high-activity tetramer forms, whereas PKM2 is found in both a highly active tetramer form and a low-activity dimer form. The switch between dimer and tetramer is allosterically modulated by the binding of ligands such as amino acids and metabolic intermediates to the regulatory C-terminal domain. Post-translational modifications at specific residues relieve this inhibition, allowing metabolic flux.
Autoinhibitory domains (AIDs)
Target domain |
43-375 (Pyruvate kinase) |
Relief mechanism |
PTM, Partner binding |
Assay |
|
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
1 structures for P52480
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P52480-F1 | Predicted | AlphaFoldDB |
27 variants for P52480
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3389056965 | 2 | P>Q | No | EVA | |
| rs13466668 | 29 | H>L | No | EVA | |
| rs3389030033 | 48 | I>F | No | EVA | |
| rs13466669 | 51 | I>V | No | EVA | |
| rs3389050321 | 55 | S>A | No | EVA | |
| rs13466678 | 60 | M>I | No | EVA | |
| rs587319478 | 60 | M>T | No | EVA | |
| rs3400217599 | 85 | A>P | No | EVA | |
| rs3389038744 | 86 | E>* | No | EVA | |
| rs3400215938 | 88 | I>N | No | EVA | |
| rs3400198605 | 89 | K>R | No | EVA | |
| rs3389052438 | 102 | P>L | No | EVA | |
| rs3389057830 | 110 | V>E | No | EVA | |
| rs13466676 | 142 | I>T | No | EVA | |
| rs3389018927 | 190 | A>G | No | EVA | |
| rs1132053671 | 218 | L>P | No | EVA | |
| rs3389025909 | 246 | R>S | No | EVA | |
| rs3389053209 | 260 | E>* | No | EVA | |
| rs3389052631 | 378 | Q>* | No | EVA | |
| rs3389054432 | 411 | A>D | No | EVA | |
| rs3389052460 | 464 | H>Q | No | EVA | |
| rs3389047837 | 492 | L>M | No | EVA | |
| rs3547362256 | 508 | V>L | No | EVA | |
| rs3389025856 | 525 | M>K | No | EVA | |
| rs3547268644 | 526 | R>C | No | EVA | |
| rs3547272837 | 529 | P>T | No | EVA | |
| rs3389052463 | 531 | P>H | No | EVA |
No associated diseases with P52480
7 regional properties for P52480
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Protein kinase domain | 284 - 537 | IPR000719 |
| domain | SH2 domain | 160 - 259 | IPR000980 |
| domain | Serine-threonine/tyrosine-protein kinase, catalytic domain | 284 - 533 | IPR001245 |
| domain | SH3 domain | 95 - 156 | IPR001452 |
| active_site | Tyrosine-protein kinase, active site | 400 - 412 | IPR008266 |
| binding_site | Protein kinase, ATP binding site | 290 - 312 | IPR017441 |
| domain | Tyrosine-protein kinase, catalytic domain | 284 - 536 | IPR020635 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.1.40 | Phosphotransferases with an alcohol group as acceptor |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
9 GO annotations of cellular component
| Name | Definition |
|---|---|
| cilium | A specialized eukaryotic organelle that consists of a filiform extrusion of the cell surface and of some cytoplasmic parts. Each cilium is largely bounded by an extrusion of the cytoplasmic (plasma) membrane, and contains a regular longitudinal array of microtubules, anchored to a basal body. |
| collagen-containing extracellular matrix | An extracellular matrix consisting mainly of proteins (especially collagen) and glycosaminoglycans (mostly as proteoglycans) that provides not only essential physical scaffolding for the cellular constituents but can also initiate crucial biochemical and biomechanical cues required for tissue morphogenesis, differentiation and homeostasis. The components are secreted by cells in the vicinity and form a sheet underlying or overlying cells such as endothelial and epithelial cells. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| mitochondrion | A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration. |
| myelin sheath | An electrically insulating fatty layer that surrounds the axons of many neurons. It is an outgrowth of glial cells |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| pyruvate kinase complex | A protein complex which is capable of pyruvate kinase activity. |
| rough endoplasmic reticulum | The rough (or granular) endoplasmic reticulum (ER) has ribosomes adhering to the outer surface; the ribosomes are the site of translation of the mRNA for those proteins which are either to be retained within the cisternae (ER-resident proteins), the proteins of the lysosomes, or the proteins destined for export from the cell. Glycoproteins undergo their initial glycosylation within the cisternae. |
13 GO annotations of molecular function
| Name | Definition |
|---|---|
| ADP binding | Binding to ADP, adenosine 5'-diphosphate. |
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| histone H3T11 kinase activity | Catalysis of the reaction |
| identical protein binding | Binding to an identical protein or proteins. |
| magnesium ion binding | Binding to a magnesium (Mg) ion. |
| mRNA binding | Binding to messenger RNA (mRNA), an intermediate molecule between DNA and protein. mRNA includes UTR and coding sequences, but does not contain introns. |
| potassium ion binding | Binding to a potassium ion (K+). |
| protein dimerization activity | The formation of a protein dimer, a macromolecular structure consists of two noncovalently associated identical or nonidentical subunits. |
| protein homodimerization activity | Binding to an identical protein to form a homodimer. |
| protein tyrosine kinase activity | Catalysis of the reaction |
| pyruvate kinase activity | Catalysis of the reaction |
| thyroid hormone binding | Binding to thyroxine (T4) or triiodothyronine (T3), tyrosine-based hormones produced by the thyroid gland. |
| transcription coactivator activity | A transcription coregulator activity that activates or increases the transcription of specific gene sets via binding to a DNA-bound DNA-binding transcription factor, either on its own or as part of a complex. Coactivators often act by altering chromatin structure and modifications. For example, one class of transcription coactivators modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-bound DNA-binding transcription factors with other transcription coregulators. A fourth class of coactivator activity is the bridging of a DNA-binding transcription factor to the general (basal) transcription machinery. The Mediator complex, which bridges sequence-specific DNA binding transcription factors and RNA polymerase, is also a transcription coactivator. |
16 GO annotations of biological process
| Name | Definition |
|---|---|
| animal organ regeneration | The regrowth of a lost or destroyed animal organ. |
| canonical glycolysis | The glycolytic process that begins with the conversion of glucose to glucose-6-phosphate by glucokinase activity. Glycolytic processes are the chemical reactions and pathways resulting in the breakdown of a carbohydrate into pyruvate, with the concomitant production of a small amount of ATP. |
| cellular response to insulin stimulus | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an insulin stimulus. Insulin is a polypeptide hormone produced by the islets of Langerhans of the pancreas in mammals, and by the homologous organs of other organisms. |
| glucose metabolic process | The chemical reactions and pathways involving glucose, the aldohexose gluco-hexose. D-glucose is dextrorotatory and is sometimes known as dextrose; it is an important source of energy for living organisms and is found free as well as combined in homo- and hetero-oligosaccharides and polysaccharides. |
| glycolytic process | The chemical reactions and pathways resulting in the breakdown of a carbohydrate into pyruvate, with the concomitant production of a small amount of ATP and the reduction of NAD(P) to NAD(P)H. Glycolysis begins with the metabolism of a carbohydrate to generate products that can enter the pathway and ends with the production of pyruvate. Pyruvate may be converted to acetyl-coenzyme A, ethanol, lactate, or other small molecules. |
| liver development | The process whose specific outcome is the progression of the liver over time, from its formation to the mature structure. The liver is an exocrine gland which secretes bile and functions in metabolism of protein and carbohydrate and fat, synthesizes substances involved in the clotting of the blood, synthesizes vitamin A, detoxifies poisonous substances, stores glycogen, and breaks down worn-out erythrocytes. |
| phosphorylation | The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide. |
| positive regulation of cytoplasmic translation | Any process that activates or increases the frequency, rate or extent of cytoplasmic translation. |
| positive regulation of sprouting angiogenesis | Any process that activates or increases the frequency, rate or extent of sprouting angiogenesis. |
| positive regulation of transcription by RNA polymerase II | Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. |
| programmed cell death | A process which begins when a cell receives an internal or external signal and activates a series of biochemical events (signaling pathway). The process ends with the death of the cell. |
| protein homotetramerization | The formation of a protein homotetramer, a macromolecular structure consisting of four noncovalently associated identical subunits. |
| protein tetramerization | The formation of a protein tetramer, a macromolecular structure consisting of four noncovalently associated identical or nonidentical subunits. |
| pyruvate biosynthetic process | The chemical reactions and pathways resulting in the formation of pyruvate, 2-oxopropanoate. |
| pyruvate metabolic process | The chemical reactions and pathways involving pyruvate, 2-oxopropanoate. |
| skeletal muscle tissue regeneration | The regrowth of skeletal muscle tissue to repair injured or damaged muscle fibers in the postnatal stage. |
12 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P52489 | PYK2 | Pyruvate kinase 2 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | SS |
| P00549 | CDC19 | Pyruvate kinase 1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | SS |
| P11979 | PKM | Pyruvate kinase PKM | Felis catus (Cat) (Felis silvestris catus) | SS |
| P00548 | PKM | Pyruvate kinase PKM | Gallus gallus (Chicken) | SS |
| Q29536 | PKLR | Pyruvate kinase PKLR | Canis lupus familiaris (Dog) (Canis familiaris) | SS |
| O62619 | PyK | Pyruvate kinase | Drosophila melanogaster (Fruit fly) | SS |
| P30613 | PKLR | Pyruvate kinase PKLR | Homo sapiens (Human) | SS |
| P14618 | PKM | Pyruvate kinase PKM | Homo sapiens (Human) | EV |
| P53657 | Pklr | Pyruvate kinase PKLR | Mus musculus (Mouse) | SS |
| P11980 | Pkm | Pyruvate kinase PKM | Rattus norvegicus (Rat) | SS |
| P12928 | Pklr | Pyruvate kinase PKLR | Rattus norvegicus (Rat) | SS |
| Q9LIK0 | PKP1 | Plastidial pyruvate kinase 1, chloroplastic | Arabidopsis thaliana (Mouse-ear cress) | PR |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MPKPHSEAGT | AFIQTQQLHA | AMADTFLEHM | CRLDIDSAPI | TARNTGIICT | IGPASRSVEM |
| 70 | 80 | 90 | 100 | 110 | 120 |
| LKEMIKSGMN | VARLNFSHGT | HEYHAETIKN | VREATESFAS | DPILYRPVAV | ALDTKGPEIR |
| 130 | 140 | 150 | 160 | 170 | 180 |
| TGLIKGSGTA | EVELKKGATL | KITLDNAYME | KCDENILWLD | YKNICKVVEV | GSKIYVDDGL |
| 190 | 200 | 210 | 220 | 230 | 240 |
| ISLQVKEKGA | DFLVTEVENG | GSLGSKKGVN | LPGAAVDLPA | VSEKDIQDLK | FGVEQDVDMV |
| 250 | 260 | 270 | 280 | 290 | 300 |
| FASFIRKAAD | VHEVRKVLGE | KGKNIKIISK | IENHEGVRRF | DEILEASDGI | MVARGDLGIE |
| 310 | 320 | 330 | 340 | 350 | 360 |
| IPAEKVFLAQ | KMMIGRCNRA | GKPVICATQM | LESMIKKPRP | TRAEGSDVAN | AVLDGADCIM |
| 370 | 380 | 390 | 400 | 410 | 420 |
| LSGETAKGDY | PLEAVRMQHL | IAREAEAAIY | HLQLFEELRR | LAPITSDPTE | AAAVGAVEAS |
| 430 | 440 | 450 | 460 | 470 | 480 |
| FKCCSGAIIV | LTKSGRSAHQ | VARYRPRAPI | IAVTRNPQTA | RQAHLYRGIF | PVLCKDAVLN |
| 490 | 500 | 510 | 520 | 530 | |
| AWAEDVDLRV | NLAMDVGKAR | GFFKKGDVVI | VLTGWRPGSG | FTNTMRVVPV | P |