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P11980 (KPYM_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pyruvate kinase PKM

EC=2.7.1.40
Alternative name(s):
Pyruvate kinase muscle isozyme
Gene names
Name:Pkm
Synonyms:Pkm2, Pykm
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length531 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

ATP + pyruvate = ADP + phosphoenolpyruvate.

Cofactor

Magnesium.

Potassium.

Enzyme regulation

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.

Pathway

Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 5/5.

Subunit structure

Monomer and homotetramer. Exists as a monomer in the absence of FBP, and reversibly associates to form a homotetramer in the presence of FBP. The monomeric form binds T3. Tetramer formation induces pyruvate kinase activity. Interacts with HERC1 formation induces pyruvate kinase activity. Interacts with HERC1, POU5F1 and PML. Interacts 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.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity.

Post-translational modification

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.

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.

Sequence similarities

Belongs to the pyruvate kinase family.

Ontologies

Keywords
   Biological processGlycolysis
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
Potassium
Pyruvate
   Molecular functionKinase
Transferase
   PTMAcetylation
Hydroxylation
Phosphoprotein
Ubl conjugation
   Technical termAllosteric enzyme
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processATP biosynthetic process

Inferred from direct assay PubMed 4273555. Source: RGD

glucose metabolic process

Inferred from direct assay PubMed 7929251. Source: RGD

glycolytic process

Inferred from direct assay PubMed 4273555PubMed 8255543. Source: RGD

liver development

Inferred from direct assay PubMed 7327170. Source: RGD

organ regeneration

Inferred from direct assay PubMed 4005043. Source: RGD

pyruvate biosynthetic process

Inferred from direct assay PubMed 4273555. Source: RGD

response to gravity

Inferred from expression pattern PubMed 12165359. Source: RGD

response to hypoxia

Inferred from expression pattern PubMed 3696161. Source: RGD

response to insulin

Inferred from expression pattern PubMed 7929251. Source: RGD

response to muscle inactivity

Inferred from expression pattern PubMed 6331066. Source: RGD

response to nutrient

Inferred from expression pattern PubMed 7929251. Source: RGD

response to organic substance

Inferred from expression pattern PubMed 6537126. Source: RGD

skeletal muscle tissue regeneration

Inferred from direct assay PubMed 145474. Source: RGD

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionADP binding

Inferred from direct assay PubMed 7040662. Source: RGD

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

magnesium ion binding

Inferred from electronic annotation. Source: InterPro

potassium ion binding

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction PubMed 17877381. Source: RGD

pyruvate kinase activity

Inferred from direct assay PubMed 4273555PubMed 8255543. Source: RGD

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform M1 (identifier: P11980-1)

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.
Isoform M2 (identifier: P11980-2)

Also known as: PKM2;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 531530Pyruvate kinase PKM
PRO_0000112092

Regions

Region307 – 531225Interaction with POU5F1 By similarity
Region389 – 43345Intersubunit contact
Region432 – 4376D-fructose 1,6-bisphosphate binding; part of allosteric site By similarity
Region514 – 5218D-fructose 1,6-bisphosphate binding; part of allosteric site By similarity

Sites

Metal binding751Potassium By similarity
Metal binding771Potassium By similarity
Metal binding1131Potassium By similarity
Metal binding1141Potassium; via carbonyl oxygen By similarity
Metal binding2721Magnesium By similarity
Metal binding2961Magnesium By similarity
Binding site701Serine By similarity
Binding site731Substrate By similarity
Binding site1061Serine By similarity
Binding site2951Substrate; via amide nitrogen By similarity
Binding site2961Substrate; via amide nitrogen By similarity
Binding site3281Substrate By similarity
Binding site4641Serine By similarity
Binding site4821D-fructose 1,6-bisphosphate; part of allosteric site By similarity
Binding site4891D-fructose 1,6-bisphosphate; part of allosteric site By similarity
Site2701Transition state stabilizer By similarity

Amino acid modifications

Modified residue371Phosphoserine By similarity
Modified residue621N6-acetyllysine By similarity
Modified residue661N6-succinyllysine By similarity
Modified residue891N6-acetyllysine By similarity
Modified residue1051Phosphotyrosine By similarity
Modified residue1481Phosphotyrosine By similarity
Modified residue1661N6-acetyllysine; alternate By similarity
Modified residue1661N6-succinyllysine; alternate By similarity
Modified residue1751Phosphotyrosine By similarity
Modified residue1951Phosphothreonine By similarity
Modified residue2661N6-acetyllysine By similarity
Modified residue2701N6-acetyllysine By similarity
Modified residue3051N6-acetyllysine By similarity
Modified residue3221N6-acetyllysine; alternate By similarity
Modified residue3221N6-succinyllysine; alternate By similarity
Modified residue40814-hydroxyproline By similarity
Modified residue4751N6-acetyllysine By similarity
Modified residue4981N6-succinyllysine By similarity

Natural variations

Alternative sequence389 – 43345VFHRL…IVLTE → IYHLQLFEELRRLAPITSDP TEAAAVGAVEASFKCCSGAI IVLTK in isoform M2.
VSP_011107

Sequences

Sequence LengthMass (Da)Tools
Isoform M1 (PKM1) [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: F0B133FDDD5991A9

FASTA53157,818
        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 

« Hide

Isoform M2 (PKM2) [UniParc] [UniParc].

Checksum: 321D9EB3500272DA
Show »

FASTA53157,781

References

[1]"The M1- and M2-type isozymes of rat pyruvate kinase are produced from the same gene by alternative RNA splicing."
Noguchi T., Inoue H., Tanaka T.
J. Biol. Chem. 261:13807-13812(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS M1 AND M2).
[2]"Rat pyruvate kinase M gene: its complete structure and characterization of the 5'-flanking region."
Takenaka M., Noguchi T., Inoue H., Yamada K., Matsuda T., Tanaka T.
J. Biol. Chem. 264:2363-2367(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS M1 AND M2), SEQUENCE REVISION.
[3]"The nucleotide sequence of a full length cDNA encoding rat pituitary pyruvate kinase."
Parkinson C., Kato H., Cheng S.
Nucleic Acids Res. 17:7106-7106(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M1).
Tissue: Pituitary.
[4]Lubec G., Afjehi-Sadat L., Chen W.-Q., Kang S.U.
Submitted (JUL-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 33-56; 74-89; 93-115; 174-186; 208-246; 279-294; 343-376; 393-400; 423-436; 476-498 AND 505-526, PROTEIN SEQUENCE OF 384-399 (ISOFORM M2), IDENTIFICATION BY MASS SPECTROMETRY.
Strain: Sprague-Dawley.
Tissue: Brain, Hippocampus and Spinal cord.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M24359 Genomic DNA. Translation: AAB93666.1.
M24359 Genomic DNA. Translation: AAB93667.1.
M14377 Genomic DNA. No translation available.
X15800 mRNA. Translation: CAA33799.1.
PIRA26186.
B26186.
RefSeqNP_445749.1. NM_053297.2. [P11980-1]
UniGeneRn.1556.

3D structure databases

ProteinModelPortalP11980.
SMRP11980. Positions 11-531.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid247659. 3 interactions.
IntActP11980. 2 interactions.

Chemistry

BindingDBP11980.
ChEMBLCHEMBL4994.

PTM databases

PhosphoSiteP11980.

2D gel databases

World-2DPAGE0004:P11980.

Proteomic databases

PaxDbP11980.
PRIDEP11980.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000015332; ENSRNOP00000015331; ENSRNOG00000011329. [P11980-2]
GeneID25630.
KEGGrno:25630.
UCSCRGD:3337. rat. [P11980-1]

Organism-specific databases

CTD5315.
RGD3337. Pkm.

Phylogenomic databases

eggNOGCOG0469.
GeneTreeENSGT00390000008859.
HOGENOMHOG000021559.
HOVERGENHBG000941.
InParanoidP11980.
KOK00873.
OMAYAAPGDQ.
OrthoDBEOG78M01Q.
PhylomeDBP11980.
TreeFamTF300390.

Enzyme and pathway databases

SABIO-RKP11980.
UniPathwayUPA00109; UER00188.

Gene expression databases

GenevestigatorP11980.

Family and domain databases

Gene3D2.40.33.10. 1 hit.
3.20.20.60. 2 hits.
3.40.1380.20. 1 hit.
InterProIPR001697. 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]
PANTHERPTHR11817. PTHR11817. 1 hit.
PfamPF00224. PK. 1 hit.
PF02887. PK_C. 1 hit.
[Graphical view]
PRINTSPR01050. PYRUVTKNASE.
SUPFAMSSF50800. SSF50800. 1 hit.
SSF51621. SSF51621. 2 hits.
SSF52935. SSF52935. 1 hit.
TIGRFAMsTIGR01064. pyruv_kin. 1 hit.
PROSITEPS00110. PYRUVATE_KINASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio607431.

Entry information

Entry nameKPYM_RAT
AccessionPrimary (citable) accession number: P11980
Secondary accession number(s): P11981
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: June 11, 2014
This is version 139 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways