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 P11980

Entry ID Method Resolution Chain Position Source
AF-P11980-F1 Predicted AlphaFoldDB

No variants for P11980

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for P11980

No associated diseases with P11980

3 regional properties for P11980

Type Name Position InterPro Accession
domain Pyruvate kinase, barrel 43 - 375 IPR015793
domain Pyruvate kinase, C-terminal 410 - 528 IPR015795
active_site Pyruvate kinase, active site 265 - 277 IPR018209

Functions

Description
EC Number 2.7.1.40 Phosphotransferases with an alcohol group as acceptor
Subcellular Localization
  • [Isoform M2]: Cytoplasm
  • Nucleus
  • Translocates to the nucleus in response to various signals, such as EGF receptor activation or apoptotic stimuli
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

6 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.
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.
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.

10 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.
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 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.

21 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.
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.
response to gravity Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a gravitational stimulus.
response to hypoxia Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level.
response to insulin Any process that results in a change in state or activity of a cell or an organism (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.
response to muscle inactivity Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a muscle inactivity stimulus.
response to nutrient Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a nutrient stimulus.
response to organic substance Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organic substance stimulus.
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
P14618 PKM Pyruvate kinase PKM Homo sapiens (Human) EV
P30613 PKLR Pyruvate kinase PKLR Homo sapiens (Human) SS
P53657 Pklr Pyruvate kinase PKLR Mus musculus (Mouse) SS
P52480 Pkm Pyruvate kinase PKM Mus musculus (Mouse) 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
MPKPDSEAGT AFIQTQQLHA AMADTFLEHM CRLDIDSAPI TARNTGIICT IGPASRSVEM
70 80 90 100 110 120
LKEMIKSGMN VARLNFSHGT HEYHAETIKN VRAATESFAS DPILYRPVAV ALDTKGPEIR
130 140 150 160 170 180
TGLIKGSGTA EVELKKGATL KITLDNAYME KCDENILWLD YKNICKVVEV GSKIYVDDGL
190 200 210 220 230 240
ISLQVKEKGA DYLVTEVENG 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 IAREAEAAVF HRLLFEELAR ASSQSTDPLE AMAMGSVEAS
430 440 450 460 470 480
YKCLAAALIV LTESGRSAHQ VARYRPRAPI IAVTRNPQTA RQAHLYRGIF PVLCKDAVLD
490 500 510 520 530
AWAEDVDLRV NLAMNVGKAR GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P