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Protein

Pyruvate kinase PKM

Gene

Pkm

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Glycolytic enzyme that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. Stimulates POU5F1-mediated transcriptional activation (By similarity).By similarity

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.

Catalytic activityi

ATP + pyruvate = ADP + phosphoenolpyruvate.

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

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. Glycolytic flux are highly dependent on de novo biosynthesis of serine and glycine, and serine is a natural ligand and allosteric activator (By similarity).By similarity

Pathwayi: glycolysis

This protein is involved in step 5 of the subpathway that synthesizes pyruvate from D-glyceraldehyde 3-phosphate.
Proteins known to be involved in the 5 steps of the subpathway in this organism are:
  1. Glyceraldehyde-3-phosphate dehydrogenase (Gapdh), Glyceraldehyde-3-phosphate dehydrogenase (Gapdh), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Glyceraldehyde-3-phosphate dehydrogenase (Gapdh), Glyceraldehyde-3-phosphate dehydrogenase (Gapdhs), Glyceraldehyde-3-phosphate dehydrogenase (Gm10358), Glyceraldehyde-3-phosphate dehydrogenase, testis-specific (Gapdhs), Glyceraldehyde-3-phosphate dehydrogenase (Gapdhs), Glyceraldehyde-3-phosphate dehydrogenase (Gm3839)
  2. Phosphoglycerate kinase (Pgk1), Phosphoglycerate kinase 2 (Pgk2), Phosphoglycerate kinase 1 (Pgk1), Phosphoglycerate kinase (Pgk1)
  3. no protein annotated in this organism
  4. Gamma-enolase (Eno2), Beta-enolase (Eno3), Alpha-enolase (Eno1), Enolase 4 (Eno4)
  5. Pyruvate kinase (Pklr), Pyruvate kinase (Pklr), Pyruvate kinase PKLR (Pklr), Pyruvate kinase (Pklr), Pyruvate kinase (Pklr), Pyruvate kinase (Pklr), Pyruvate kinase PKM (Pkm)
This subpathway is part of the pathway glycolysis, which is itself part of Carbohydrate degradation.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes pyruvate from D-glyceraldehyde 3-phosphate, the pathway glycolysis and in Carbohydrate degradation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei70SerineBy similarity1
Binding sitei73SubstrateBy similarity1
Metal bindingi75PotassiumBy similarity1
Metal bindingi77PotassiumBy similarity1
Binding sitei106SerineBy similarity1
Metal bindingi113PotassiumBy similarity1
Metal bindingi114Potassium; via carbonyl oxygenBy similarity1
Sitei270Transition state stabilizerBy similarity1
Metal bindingi272MagnesiumBy similarity1
Binding sitei295Substrate; via amide nitrogenBy similarity1
Metal bindingi296MagnesiumBy similarity1
Binding sitei296Substrate; via amide nitrogenBy similarity1
Binding sitei328SubstrateBy similarity1
Sitei433Crucial for phosphotyrosine bindingBy similarity1
Binding sitei464SerineBy similarity1
Binding sitei482D-fructose 1,6-bisphosphate; part of allosteric siteBy similarity1
Binding sitei489D-fructose 1,6-bisphosphate; part of allosteric siteBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionAllosteric enzyme, Kinase, Transferase
Biological processGlycolysis
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Potassium, Pyruvate

Enzyme and pathway databases

ReactomeiR-MMU-6798695 Neutrophil degranulation
R-MMU-70171 Glycolysis
SABIO-RKiP52480
UniPathwayiUPA00109; UER00188

Names & Taxonomyi

Protein namesi
Recommended name:
Pyruvate kinase PKM (EC:2.7.1.40)
Alternative name(s):
Pyruvate kinase muscle isozyme
Gene namesi
Name:Pkm
Synonyms:Pk3, Pkm2, Pykm
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:97591 Pkm

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001120891 – 531Pyruvate kinase PKMAdd BLAST531

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3N6,N6,N6-trimethyllysineBy similarity1
Modified residuei37PhosphoserineBy similarity1
Modified residuei41PhosphothreonineBy similarity1
Modified residuei62N6-acetyllysineCombined sources1
Modified residuei66N6-succinyllysineCombined sources1
Modified residuei89N6-acetyllysineBy similarity1
Modified residuei97PhosphoserineBy similarity1
Modified residuei100PhosphoserineBy similarity1
Modified residuei105PhosphotyrosineCombined sources1
Cross-linki115Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei127PhosphoserineBy similarity1
Modified residuei148PhosphotyrosineCombined sources1
Modified residuei166N6-acetyllysine; alternateCombined sources1
Modified residuei166N6-succinyllysine; alternateCombined sources1
Cross-linki166Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateBy similarity
Modified residuei175PhosphotyrosineBy similarity1
Modified residuei195PhosphothreonineBy similarity1
Modified residuei266N6-acetyllysine; alternateBy similarity1
Cross-linki266Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei270N6-acetyllysine; alternateCombined sources1
Cross-linki270Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei305N6-acetyllysineBy similarity1
Modified residuei322N6-acetyllysine; alternateCombined sources1
Modified residuei322N6-succinyllysine; alternateCombined sources1
Modified residuei4034-hydroxyprolineBy similarity1
Modified residuei4084-hydroxyprolineBy similarity1
Modified residuei433N6-acetyllysineBy similarity1
Modified residuei475N6-acetyllysineCombined sources1
Modified residuei498N6-succinyllysineCombined sources1

Post-translational modificationi

ISGylated.1 Publication
Under hypoxia, hydroxylated by EGLN3.By similarity
Acetylation at Lys-305 is stimulated by high glucose concentration, it decreases enzyme activity and promotes its lysosomal-dependent degradation via chaperone-mediated autophagy.By similarity

Keywords - PTMi

Acetylation, Hydroxylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP52480
MaxQBiP52480
PaxDbiP52480
PeptideAtlasiP52480
PRIDEiP52480

2D gel databases

REPRODUCTION-2DPAGEiIPI00407130
P52480
SWISS-2DPAGEiP52480

PTM databases

iPTMnetiP52480
PhosphoSitePlusiP52480
SwissPalmiP52480

Expressioni

Tissue specificityi

Embryonic stem cells and embryonal carcinoma cells.1 Publication

Gene expression databases

BgeeiENSMUSG00000032294
CleanExiMM_PKM2
ExpressionAtlasiP52480 baseline and differential
GenevisibleiP52480 MM

Interactioni

Subunit structurei

Monomer and homotetramer. Exists as a monomer in the absence of fructose 1,6 bi-phosphate (FBP), and reversibly associates to form a homotetramer in the presence of FBP. The monomeric form binds T3. Tetramer formation induces pyruvate kinase activity. 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 (By similarity). Interacts (isoform M2, but not isoform M1) with TRIM35; this interaction prevents FGFR1-dependent tyrosine phosphorylation (By similarity).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202191, 18 interactors
ComplexPortaliCPX-3059 PKM2 pyruvate kinase complex (tetramer) [P52480-1]
CPX-3060 PKM2 protein kinase complex (dimer) [P52480-1]
CPX-3096 PKM1 pyruvate kinase complex [P52480-2]
DIPiDIP-40536N
IntActiP52480, 30 interactors
MINTiP52480
STRINGi10090.ENSMUSP00000034834

Structurei

3D structure databases

ProteinModelPortaliP52480
SMRiP52480
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni307 – 531Interaction with POU5F1By similarityAdd BLAST225
Regioni389 – 433Intersubunit contactAdd BLAST45
Regioni432 – 437D-fructose 1,6-bisphosphate binding; part of allosteric siteBy similarity6
Regioni514 – 521D-fructose 1,6-bisphosphate binding; part of allosteric siteBy similarity8

Sequence similaritiesi

Belongs to the pyruvate kinase family.Curated

Phylogenomic databases

eggNOGiKOG2323 Eukaryota
COG0469 LUCA
GeneTreeiENSGT00390000008859
HOVERGENiHBG000941
InParanoidiP52480
KOiK00873
OMAiKHEAIEQ
OrthoDBiEOG091G0597
PhylomeDBiP52480
TreeFamiTF300390

Family and domain databases

CDDicd00288 Pyruvate_Kinase, 1 hit
Gene3Di2.40.33.10, 1 hit
3.40.1380.20, 2 hits
InterProiView protein in InterPro
IPR001697 Pyr_Knase
IPR015813 Pyrv/PenolPyrv_Kinase-like_dom
IPR011037 Pyrv_Knase-like_insert_dom_sf
IPR018209 Pyrv_Knase_AS
IPR015793 Pyrv_Knase_brl
IPR015795 Pyrv_Knase_C
IPR036918 Pyrv_Knase_C_sf
IPR015806 Pyrv_Knase_insert_dom_sf
PANTHERiPTHR11817 PTHR11817, 1 hit
PfamiView protein in Pfam
PF00224 PK, 1 hit
PF02887 PK_C, 1 hit
PRINTSiPR01050 PYRUVTKNASE
SUPFAMiSSF50800 SSF50800, 1 hit
SSF51621 SSF51621, 2 hits
SSF52935 SSF52935, 1 hit
TIGRFAMsiTIGR01064 pyruv_kin, 1 hit
PROSITEiView protein in PROSITE
PS00110 PYRUVATE_KINASE, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform M2 (identifier: P52480-1) [UniParc]FASTAAdd to basket
Also known as: PKM2

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPKPHSEAGT AFIQTQQLHA AMADTFLEHM CRLDIDSAPI TARNTGIICT
60 70 80 90 100
IGPASRSVEM LKEMIKSGMN VARLNFSHGT HEYHAETIKN VREATESFAS
110 120 130 140 150
DPILYRPVAV ALDTKGPEIR TGLIKGSGTA EVELKKGATL KITLDNAYME
160 170 180 190 200
KCDENILWLD YKNICKVVEV GSKIYVDDGL ISLQVKEKGA DFLVTEVENG
210 220 230 240 250
GSLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV FASFIRKAAD
260 270 280 290 300
VHEVRKVLGE KGKNIKIISK IENHEGVRRF DEILEASDGI MVARGDLGIE
310 320 330 340 350
IPAEKVFLAQ KMMIGRCNRA GKPVICATQM LESMIKKPRP TRAEGSDVAN
360 370 380 390 400
AVLDGADCIM LSGETAKGDY PLEAVRMQHL IAREAEAAIY HLQLFEELRR
410 420 430 440 450
LAPITSDPTE AAAVGAVEAS FKCCSGAIIV LTKSGRSAHQ VARYRPRAPI
460 470 480 490 500
IAVTRNPQTA RQAHLYRGIF PVLCKDAVLN AWAEDVDLRV NLAMDVGKAR
510 520 530
GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P
Length:531
Mass (Da):57,845
Last modified:May 1, 2007 - v4
Checksum:i34CBBC01BC0C047D
GO
Isoform M1 (identifier: P52480-2) [UniParc]FASTAAdd to basket
Also known as: PKM1

The sequence of this isoform differs from the canonical sequence as follows:
     389-433: IYHLQLFEEL...CSGAIIVLTK → MFHRLLFEEL...LAAALIVLTE

Show »
Length:531
Mass (Da):57,985
Checksum:iD0D163786CC6D4A6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti8A → V in CAA65761 (PubMed:9545585).Curated1
Sequence conflicti121T → A in BAE30642 (PubMed:16141072).Curated1
Sequence conflicti121T → A in BAE32031 (PubMed:16141072).Curated1
Sequence conflicti158W → R in BAA07457 (PubMed:7612666).Curated1
Sequence conflicti166K → E in BAE42098 (PubMed:16141072).Curated1
Sequence conflicti170V → L in BAE30642 (PubMed:16141072).Curated1
Sequence conflicti170V → L in BAE32031 (PubMed:16141072).Curated1
Sequence conflicti177D → G in BAE42199 (PubMed:16141072).Curated1
Sequence conflicti230K → R in BAE30642 (PubMed:16141072).Curated1
Sequence conflicti230K → R in BAE32031 (PubMed:16141072).Curated1
Sequence conflicti299I → T in BAA07457 (PubMed:7612666).Curated1
Sequence conflicti309A → S in BAA07457 (PubMed:7612666).Curated1
Sequence conflicti327A → S in BAA07457 (PubMed:7612666).Curated1
Sequence conflicti327A → S in CAA65761 (PubMed:9545585).Curated1
Sequence conflicti333S → I in BAA07457 (PubMed:7612666).Curated1
Sequence conflicti333S → I in CAA65761 (PubMed:9545585).Curated1
Sequence conflicti485D → N in BAE33055 (PubMed:16141072).Curated1
Sequence conflicti485D → N in BAE42192 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_025057389 – 433IYHLQ…IVLTK → MFHRLLFEELVRASSHSTDL MEAMAMGSVEASYKCLAAAL IVLTE in isoform M1. 1 PublicationAdd BLAST45

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D38379 mRNA Translation: BAA07457.1
X97047 mRNA Translation: CAA65761.1
AK002341 mRNA Translation: BAB22025.1
AK135397 mRNA Translation: BAE22519.1
AK151724 mRNA Translation: BAE30642.1
AK153483 mRNA Translation: BAE32031.1
AK155110 mRNA Translation: BAE33055.1
AK155655 mRNA Translation: BAE33370.1
AK170892 mRNA Translation: BAE42098.1
AK168943 mRNA Translation: BAE40751.1
AK171023 mRNA Translation: BAE42192.1
AK171033 mRNA Translation: BAE42199.1
AC160637 Genomic DNA No translation available.
BC016619 mRNA Translation: AAH16619.1
BC094663 mRNA Translation: AAH94663.1
CCDSiCCDS40659.1 [P52480-1]
CCDS57681.1 [P52480-2]
PIRiS55921
RefSeqiNP_001240812.1, NM_001253883.1 [P52480-2]
NP_035229.2, NM_011099.3 [P52480-1]
XP_006510918.1, XM_006510855.1 [P52480-1]
XP_011240975.1, XM_011242673.1 [P52480-2]
UniGeneiMm.326167
Mm.488724

Genome annotation databases

EnsembliENSMUST00000034834; ENSMUSP00000034834; ENSMUSG00000032294 [P52480-1]
ENSMUST00000163694; ENSMUSP00000128770; ENSMUSG00000032294 [P52480-2]
GeneIDi18746
KEGGimmu:18746
UCSCiuc009pyf.2 mouse [P52480-1]
uc009pyh.2 mouse [P52480-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKPYM_MOUSE
AccessioniPrimary (citable) accession number: P52480
Secondary accession number(s): Q3TBV8
, Q3TBW5, Q3TC59, Q3U1X3, Q3U5P6, Q4VC20, Q64484, Q91YI8, Q9CWB1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 1, 2007
Last modified: June 20, 2018
This is version 189 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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