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Protein

Pyruvate kinase PKM

Gene

PKM

Organism
Felis catus (Cat) (Felis silvestris catus)
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:

Activity 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 (GAPDHS), Glyceraldehyde-3-phosphate dehydrogenase (GAPDHS), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
  2. Phosphoglycerate kinase, Phosphoglycerate kinase (PGK2), Phosphoglycerate kinase (PGK1), Phosphoglycerate kinase (PGK1), Phosphoglycerate kinase (PGK1)
  3. no protein annotated in this organism
  4. no protein annotated in this organism
  5. Pyruvate kinase PKM (PKM), Pyruvate kinase (LOC101081229), Pyruvate kinase, Pyruvate kinase (PKLR), Pyruvate kinase, Pyruvate kinase, Pyruvate kinase (PKLR), Pyruvate kinase, Pyruvate kinase (pklr), Pyruvate kinase
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
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

  • ATP binding Source: UniProtKB-KW
  • kinase activity Source: UniProtKB-KW
  • magnesium ion binding Source: InterPro
  • potassium ion binding Source: InterPro
  • pyruvate kinase activity Source: GO_Central

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

UniPathwayi
UPA00109;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:PKM2
OrganismiFelis catus (Cat) (Felis silvestris catus)
Taxonomic identifieri9685 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraFeliformiaFelidaeFelinaeFelis
Proteomesi
  • UP000011712 Componenti: Unplaced

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
Initiator methionineiRemoved1 Publication
ChainiPRO_00001120872 – 531Pyruvate kinase PKMAdd BLAST530

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserine1 Publication1
Modified residuei3N6,N6,N6-trimethyllysineBy similarity1
Modified residuei37PhosphoserineBy similarity1
Modified residuei41PhosphothreonineBy similarity1
Modified residuei62N6-acetyllysineBy similarity1
Modified residuei66N6-succinyllysineBy similarity1
Modified residuei89N6-acetyllysineBy similarity1
Modified residuei97PhosphoserineBy similarity1
Modified residuei100PhosphoserineBy similarity1
Modified residuei105PhosphotyrosineBy similarity1
Cross-linki115Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei127PhosphoserineBy similarity1
Modified residuei148PhosphotyrosineBy similarity1
Modified residuei166N6-acetyllysine; alternateBy similarity1
Modified residuei166N6-succinyllysine; alternateBy similarity1
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; alternateBy similarity1
Cross-linki270Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei305N6-acetyllysineBy similarity1
Modified residuei322N6-acetyllysine; alternateBy similarity1
Modified residuei322N6-succinyllysine; alternateBy similarity1
Modified residuei475N6-acetyllysineBy similarity1
Modified residuei498N6-succinyllysineBy similarity1

Post-translational modificationi

ISGylated.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, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiP11979

PTM databases

iPTMnetiP11979

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). Interacts with JMJD8 (By similarity).By similarity

Protein-protein interaction databases

STRINGi9685.ENSFCAP00000000606

Structurei

Secondary structure

1531
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP11979
SMRiP11979
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11979

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni307 – 531Interaction with POU5F1By similarityAdd BLAST225
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
HOGENOMiHOG000021559
HOVERGENiHBG000941
InParanoidiP11979
TreeFamiTF300390

Family and domain databases

CDDicd00288 Pyruvate_Kinase, 1 hit
Gene3Di2.40.33.10, 1 hit
3.40.1380.20, 1 hit
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, 1 hit
SSF52935 SSF52935, 1 hit
TIGRFAMsiTIGR01064 pyruv_kin, 1 hit
PROSITEiView protein in PROSITE
PS00110 PYRUVATE_KINASE, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform M1 (identifier: P11979-1) [UniParc]FASTAAdd to basket
Also known as: PKM1

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
MSKPHSDVGT AFIQTQQLHA AMADTFLEHM CRLDIDSPPI TARNTGIICT
60 70 80 90 100
IGPASRSVEI LKEMIKSGMN VARLNFSHGT HEYHAETIKN VRAATESFAS
110 120 130 140 150
DPIRYRPVAV ALDTKGPEIR TGLIKGSGTA EVELKKGATL KITLDNAYME
160 170 180 190 200
KCDENVLWLD YKNICKVVEV GSKVYVDDGL ISLLVKEKGA DFLVTEVENG
210 220 230 240 250
GSLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV FASFIRKASD
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 IAREAEAAMF HRKLFEELVR
410 420 430 440 450
GSSHSTDLME AMAMGSVEAS YKCLAAALIV LTESGRSAHQ VARYRPRAPI
460 470 480 490 500
IAVTRNHQTA RQAHLYRGIF PVVCKDPVQE AWAEDVDLRV NLAMNVGKAR
510 520 530
GFFKHGDVVI VLTGWRPGSG FTNTMRVVPV P
Length:531
Mass (Da):58,046
Last modified:January 23, 2007 - v2
Checksum:i302475E32D6109A8
GO
Isoform M2 (identifier: P11979-2)
Also known as: PKM2
Sequence is not available
Length:
Mass (Da):

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti209V → A AA sequence (Ref. 2) Curated1
Sequence conflicti226 – 227IQ → FE AA sequence (Ref. 2) Curated2
Sequence conflicti232G → Q AA sequence (Ref. 2) Curated1
Sequence conflicti235Q → R AA sequence (Ref. 2) Curated1

Sequence databases

PIRiA25091

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

PIRiA25091

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1PKMX-ray2.60A2-531[»]
ProteinModelPortaliP11979
SMRiP11979
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9685.ENSFCAP00000000606

PTM databases

iPTMnetiP11979

Proteomic databases

PRIDEiP11979

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiKOG2323 Eukaryota
COG0469 LUCA
HOGENOMiHOG000021559
HOVERGENiHBG000941
InParanoidiP11979
TreeFamiTF300390

Enzyme and pathway databases

UniPathwayi
UPA00109;UER00188

Miscellaneous databases

EvolutionaryTraceiP11979

Family and domain databases

CDDicd00288 Pyruvate_Kinase, 1 hit
Gene3Di2.40.33.10, 1 hit
3.40.1380.20, 1 hit
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, 1 hit
SSF52935 SSF52935, 1 hit
TIGRFAMsiTIGR01064 pyruv_kin, 1 hit
PROSITEiView protein in PROSITE
PS00110 PYRUVATE_KINASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiKPYM_FELCA
AccessioniPrimary (citable) accession number: P11979
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 160 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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