AiPD: Autoinhibited Protein Database

O62619

Gene name	PyK (CG7070)
Protein name	Pyruvate kinase
Names	PK , EC 2.7.1.40
Species	Drosophila melanogaster (Fruit fly)
KEGG Pathway	dme:Dmel_CG7070
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)

392-533 (C-terminal domain) SS

Target domain	46-378 (Pyruvate kinase)
Relief mechanism	PTM, Partner binding
Assay

AID

392-533 (C-terminal domain)

Target domain

46-378 (Pyruvate kinase)

Relief mechanism

PTM (de-glycosylation of residues in the regulatory domain facilitates tetramer formation. Other diverse modifications are involved in the activity regulation), Partner binding (Mucin-1 to the C-terminal domain increases PKM2 activity, while JMJD5 and HSP40 reduce the activity.),

Assay

Accessory elements

No accessory elements

References

Zhang Z et al. (2019) "PKM2, function and expression and regulation", Cell & bioscience, 9, 52

Zahra K et al. (2020) "Pyruvate Kinase M2 and Cancer: The Role of PKM2 in Promoting Tumorigenesis", Frontiers in oncology, 10, 159

Autoinhibited structure

Activated structure

1 structures for O62619

Entry ID	Method	Resolution	Chain	Position	Source
AF-O62619-F1	Predicted				AlphaFoldDB

No variants for O62619

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
No variants for O62619

No associated diseases with O62619

3 regional properties for O62619

Type	Name	Position	InterPro Accession
domain	Cyclic nucleotide-binding domain	427 - 540	IPR000595
domain	Ion transport domain	93 - 355	IPR005821
domain	Ion transport N-terminal	49 - 91	IPR013621

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

3 GO annotations of cellular component

Name	Definition
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.
P granule	A small cytoplasmic, non-membranous RNA/protein complex aggregate in the primordial germ cells of many higher eukaryotes.

5 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
kinase activity	Catalysis of the transfer of a phosphate group, usually from ATP, to a substrate molecule.
magnesium ion binding	Binding to a magnesium (Mg) ion.
potassium ion binding	Binding to a potassium ion (K+).
pyruvate kinase activity	Catalysis of the reaction

8 GO annotations of biological process

Name	Definition
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 homeostasis	Any process involved in the maintenance of an internal steady state of glucose within an organism or cell.
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.
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.
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 sucrose	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 sucrose stimulus.

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
P30613	PKLR	Pyruvate kinase PKLR	Homo sapiens (Human)	SS
P14618	PKM	Pyruvate kinase PKM	Homo sapiens (Human)	EV
P52480	Pkm	Pyruvate kinase PKM	Mus musculus (Mouse)	SS
P53657	Pklr	Pyruvate kinase PKLR	Mus musculus (Mouse)	SS
P12928	Pklr	Pyruvate kinase PKLR	Rattus norvegicus (Rat)	SS
P11980	Pkm	Pyruvate kinase PKM	Rattus norvegicus (Rat)	SS
Q9LIK0	PKP1	Plastidial pyruvate kinase 1, chloroplastic	Arabidopsis thaliana (Mouse-ear cress)	PR

10	20	30	40	50	60
MVNVTIYDEA	PQLKPNEVPQ	NMAAGADTQL	EHMCRLQFDS	PVPHVRLSGI	VCTIGPASSS
70	80	90	100	110	120
VEMLEKMMAT	GMNIARMNFS	HGSHEYHAAT	VANVRQAVKN	YSAKLGYEHP	VAIALDTKGP
130	140	150	160	170	180
EIRTGLIGGS	GTAEIELKKG	EKIKLTTNKE	FLEKGSLEIV	YVDYENIVNV	VKPGNRVFVD
190	200	210	220	230	240
DGLISLIVRE	VGKDSLTCEV	ENGGSLGSRK	GVNLPGVPVD	LPAVSEKDKS	DLLFGVEQEV
250	260	270	280	290	300
DMIFASFIRN	AAALTEIRKV	LGEKGKNIKI	ISKIENQQGM	HNLDEIIEAG	DGIMVARGDL
310	320	330	340	350	360
GIEIPAEKVF	LAQKAMIARC	NKAGKPVICA	TQMLESMVKK	PRPTRAEISD	VANAVLDGAD
370	380	390	400	410	420
CVMLSGETAK	GEYPLECVLT	MAKTCKEAEA	ALWHQNLFND	LVRGAGTIDA	SHAAAIAAVE
430	440	450	460	470	480
AATKAKASAI	VVITTSGKSA	FQVSKYRPRC	PIIAVTRFAQ	TARQAHLYRG	LVPLIYKEPG
490	500	510	520	530
LGDWLKDVDV	RVQFGLQVGK	KNGFIKTGDS	VVVVTGWKQG	SGFTNTIRIV	TVE