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Protein

Pyruvate kinase PKM

Gene

Pkm

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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, Glyceraldehyde-3-phosphate dehydrogenase, Glyceraldehyde-3-phosphate dehydrogenase, testis-specific (Gapdhs), Glyceraldehyde-3-phosphate dehydrogenase, Glyceraldehyde-3-phosphate dehydrogenase, Glyceraldehyde-3-phosphate dehydrogenase (LOC108351137), Glyceraldehyde-3-phosphate dehydrogenase (Gapdh-ps2), Glyceraldehyde-3-phosphate dehydrogenase (Gapdhs), Glyceraldehyde-3-phosphate dehydrogenase (RGD1562758)
  2. Phosphoglycerate kinase 1 (Pgk1)
  3. no protein annotated in this organism
  4. Alpha-enolase (Eno1), Beta-enolase (Eno3), Gamma-enolase (Eno2)
  5. Pyruvate kinase PKLR (Pklr), Pyruvate kinase PKM (Pkm), Pyruvate kinase (Pklr), Pyruvate kinase (LOC100362738), Pyruvate kinase (Pkm), Pyruvate kinase (Pklr), Pyruvate kinase (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
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

  • ADP binding Source: RGD
  • ATP binding Source: UniProtKB-KW
  • kinase activity Source: UniProtKB-KW
  • magnesium ion binding Source: InterPro
  • poly(A) RNA binding Source: Ensembl
  • potassium ion binding Source: InterPro
  • pyruvate kinase activity Source: RGD

GO - Biological processi

  • animal organ regeneration Source: RGD
  • ATP biosynthetic process Source: RGD
  • glucose metabolic process Source: RGD
  • glycolytic process Source: RGD
  • liver development Source: RGD
  • programmed cell death Source: Ensembl
  • pyruvate biosynthetic process Source: RGD
  • response to gravity Source: RGD
  • response to hypoxia Source: RGD
  • response to insulin Source: RGD
  • response to muscle inactivity Source: RGD
  • response to nutrient Source: RGD
  • response to organic substance Source: RGD
  • skeletal muscle tissue regeneration Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Glycolysis

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Potassium, Pyruvate

Enzyme and pathway databases

ReactomeiR-RNO-6798695. Neutrophil degranulation.
R-RNO-70171. Glycolysis.
SABIO-RKP11980.
UniPathwayiUPA00109; UER00188.

Protein family/group databases

MoonProtiP11980.

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, Pykm
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi3337. Pkm.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: Translocates to the nucleus in response to different apoptotic stimuli. Nuclear translocation is sufficient to induce cell death that is caspase independent, isoform-specific and independent of its enzymatic activity.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL4994.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001120922 – 531Pyruvate kinase PKMAdd BLAST530

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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 residuei97PhosphoserineCombined sources1
Modified residuei100PhosphoserineCombined sources1
Modified residuei105PhosphotyrosineBy similarity1
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-acetyllysineBy similarity1
Modified residuei270N6-acetyllysineBy similarity1
Modified residuei305N6-acetyllysineBy similarity1
Modified residuei322N6-acetyllysine; alternateBy similarity1
Modified residuei322N6-succinyllysine; alternateBy similarity1
Modified residuei4084-hydroxyprolineBy similarity1
Modified residuei475N6-acetyllysineBy similarity1
Modified residuei498N6-succinyllysineBy similarity1

Post-translational modificationi

ISGylated.By similarity
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

PaxDbiP11980.
PRIDEiP11980.

2D gel databases

World-2DPAGE0004:P11980.

PTM databases

iPTMnetiP11980.
PhosphoSitePlusiP11980.

Expressioni

Gene expression databases

BgeeiENSRNOG00000011329.
ExpressionAtlasiP11980. baseline and differential.
GenevisibleiP11980. RN.

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

Protein-protein interaction databases

BioGridi247659. 3 interactors.
IntActiP11980. 2 interactors.
STRINGi10116.ENSRNOP00000015331.

Chemistry databases

BindingDBiP11980.

Structurei

3D structure databases

ProteinModelPortaliP11980.
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.
HOGENOMiHOG000021559.
HOVERGENiHBG000941.
InParanoidiP11980.
KOiK00873.
OMAiTTFLEIN.
OrthoDBiEOG091G0597.
PhylomeDBiP11980.
TreeFamiTF300390.

Family and domain databases

Gene3Di2.40.33.10. 1 hit.
3.20.20.60. 2 hits.
3.40.1380.20. 1 hit.
InterProiIPR001697. Pyr_Knase.
IPR015813. Pyrv/PenolPyrv_Kinase-like_dom.
IPR011037. Pyrv_Knase-like_insert_dom.
IPR015794. Pyrv_Knase_a/b.
IPR018209. Pyrv_Knase_AS.
IPR015793. Pyrv_Knase_brl.
IPR015795. Pyrv_Knase_C.
IPR015806. Pyrv_Knase_insert_dom.
[Graphical view]
PANTHERiPTHR11817. PTHR11817. 1 hit.
PfamiPF00224. PK. 1 hit.
PF02887. PK_C. 1 hit.
[Graphical view]
PRINTSiPR01050. PYRUVTKNASE.
SUPFAMiSSF50800. SSF50800. 1 hit.
SSF51621. SSF51621. 2 hits.
SSF52935. SSF52935. 1 hit.
TIGRFAMsiTIGR01064. pyruv_kin. 1 hit.
PROSITEiPS00110. PYRUVATE_KINASE. 1 hit.
[Graphical view]

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: P11980-1) [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
MPKPDSEAGT AFIQTQQLHA AMADTFLEHM CRLDIDSAPI TARNTGIICT
60 70 80 90 100
IGPASRSVEM LKEMIKSGMN VARLNFSHGT HEYHAETIKN VRAATESFAS
110 120 130 140 150
DPILYRPVAV ALDTKGPEIR TGLIKGSGTA EVELKKGATL KITLDNAYME
160 170 180 190 200
KCDENILWLD YKNICKVVEV GSKIYVDDGL ISLQVKEKGA DYLVTEVENG
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 IAREAEAAVF HRLLFEELAR
410 420 430 440 450
ASSQSTDPLE AMAMGSVEAS YKCLAAALIV LTESGRSAHQ VARYRPRAPI
460 470 480 490 500
IAVTRNPQTA RQAHLYRGIF PVLCKDAVLD AWAEDVDLRV NLAMNVGKAR
510 520 530
GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P
Length:531
Mass (Da):57,818
Last modified:January 23, 2007 - v3
Checksum:iF0B133FDDD5991A9
GO
Isoform M2 (identifier: P11980-2) [UniParc] [UniParc]FASTAAdd to basket
Also known as: PKM2

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

Show »
Length:531
Mass (Da):57,781
Checksum:i321D9EB3500272DA
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011107389 – 433VFHRL…IVLTE → IYHLQLFEELRRLAPITSDP TEAAAVGAVEASFKCCSGAI IVLTK in isoform M2. CuratedAdd BLAST45

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M24359 Genomic DNA. Translation: AAB93666.1.
M24359 Genomic DNA. Translation: AAB93667.1.
M14377 Genomic DNA. No translation available.
X15800 mRNA. Translation: CAA33799.1.
PIRiA26186.
B26186.
RefSeqiNP_445749.1. NM_053297.2. [P11980-1]
XP_006243250.2. XM_006243188.3. [P11980-2]
UniGeneiRn.1556.

Genome annotation databases

EnsembliENSRNOT00000015332; ENSRNOP00000015331; ENSRNOG00000011329. [P11980-1]
GeneIDi25630.
KEGGirno:25630.
UCSCiRGD:3337. rat. [P11980-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M24359 Genomic DNA. Translation: AAB93666.1.
M24359 Genomic DNA. Translation: AAB93667.1.
M14377 Genomic DNA. No translation available.
X15800 mRNA. Translation: CAA33799.1.
PIRiA26186.
B26186.
RefSeqiNP_445749.1. NM_053297.2. [P11980-1]
XP_006243250.2. XM_006243188.3. [P11980-2]
UniGeneiRn.1556.

3D structure databases

ProteinModelPortaliP11980.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247659. 3 interactors.
IntActiP11980. 2 interactors.
STRINGi10116.ENSRNOP00000015331.

Chemistry databases

BindingDBiP11980.
ChEMBLiCHEMBL4994.

Protein family/group databases

MoonProtiP11980.

PTM databases

iPTMnetiP11980.
PhosphoSitePlusiP11980.

2D gel databases

World-2DPAGE0004:P11980.

Proteomic databases

PaxDbiP11980.
PRIDEiP11980.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000015332; ENSRNOP00000015331; ENSRNOG00000011329. [P11980-1]
GeneIDi25630.
KEGGirno:25630.
UCSCiRGD:3337. rat. [P11980-1]

Organism-specific databases

CTDi5315.
RGDi3337. Pkm.

Phylogenomic databases

eggNOGiKOG2323. Eukaryota.
COG0469. LUCA.
GeneTreeiENSGT00390000008859.
HOGENOMiHOG000021559.
HOVERGENiHBG000941.
InParanoidiP11980.
KOiK00873.
OMAiTTFLEIN.
OrthoDBiEOG091G0597.
PhylomeDBiP11980.
TreeFamiTF300390.

Enzyme and pathway databases

UniPathwayiUPA00109; UER00188.
ReactomeiR-RNO-6798695. Neutrophil degranulation.
R-RNO-70171. Glycolysis.
SABIO-RKP11980.

Miscellaneous databases

PROiP11980.

Gene expression databases

BgeeiENSRNOG00000011329.
ExpressionAtlasiP11980. baseline and differential.
GenevisibleiP11980. RN.

Family and domain databases

Gene3Di2.40.33.10. 1 hit.
3.20.20.60. 2 hits.
3.40.1380.20. 1 hit.
InterProiIPR001697. Pyr_Knase.
IPR015813. Pyrv/PenolPyrv_Kinase-like_dom.
IPR011037. Pyrv_Knase-like_insert_dom.
IPR015794. Pyrv_Knase_a/b.
IPR018209. Pyrv_Knase_AS.
IPR015793. Pyrv_Knase_brl.
IPR015795. Pyrv_Knase_C.
IPR015806. Pyrv_Knase_insert_dom.
[Graphical view]
PANTHERiPTHR11817. PTHR11817. 1 hit.
PfamiPF00224. PK. 1 hit.
PF02887. PK_C. 1 hit.
[Graphical view]
PRINTSiPR01050. PYRUVTKNASE.
SUPFAMiSSF50800. SSF50800. 1 hit.
SSF51621. SSF51621. 2 hits.
SSF52935. SSF52935. 1 hit.
TIGRFAMsiTIGR01064. pyruv_kin. 1 hit.
PROSITEiPS00110. PYRUVATE_KINASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKPYM_RAT
AccessioniPrimary (citable) accession number: P11980
Secondary accession number(s): P11981
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 160 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.