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P11979 (KPYM_FELCA) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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
OrganismFelis catus (Cat) (Felis silvestris catus) [Reference proteome]
Taxonomic identifier9685 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraFeliformiaFelidaeFelinaeFelis

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 POU5F1 and PML By similarity.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity.

Post-translational modification

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. Ref.1

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.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Select]
Isoform M1 (identifier: P11979-1)

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: P11979-2)

Also known as: PKM2;

The sequence of this isoform is not available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.1
Chain2 – 531530Pyruvate kinase PKM
PRO_0000112087

Regions

Region307 – 531225Interaction with POU5F1 By similarity
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 residue21N-acetylserine Ref.1
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 residue4751N6-acetyllysine By similarity
Modified residue4981N6-succinyllysine By similarity

Experimental info

Sequence conflict2091V → A AA sequence Ref.2
Sequence conflict226 – 2272IQ → FE AA sequence Ref.2
Sequence conflict2321G → Q AA sequence Ref.2
Sequence conflict2351Q → R AA sequence Ref.2

Secondary structure

....................................................................................... 531
Helix Strand Turn

Details...

Sequences

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

Last modified January 23, 2007. Version 2.
Checksum: 302475E32D6109A8

FASTA53158,046
        10         20         30         40         50         60 
MSKPHSDVGT AFIQTQQLHA AMADTFLEHM CRLDIDSPPI TARNTGIICT IGPASRSVEI 

        70         80         90        100        110        120 
LKEMIKSGMN VARLNFSHGT HEYHAETIKN VRAATESFAS DPIRYRPVAV ALDTKGPEIR 

       130        140        150        160        170        180 
TGLIKGSGTA EVELKKGATL KITLDNAYME KCDENVLWLD YKNICKVVEV GSKVYVDDGL 

       190        200        210        220        230        240 
ISLLVKEKGA DFLVTEVENG GSLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV 

       250        260        270        280        290        300 
FASFIRKASD 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 IAREAEAAMF HRKLFEELVR GSSHSTDLME AMAMGSVEAS 

       430        440        450        460        470        480 
YKCLAAALIV LTESGRSAHQ VARYRPRAPI IAVTRNHQTA RQAHLYRGIF PVVCKDPVQE 

       490        500        510        520        530 
AWAEDVDLRV NLAMNVGKAR GFFKHGDVVI VLTGWRPGSG FTNTMRVVPV P 

« Hide

Isoform M2 (PKM2) (Sequence not available).

References

[1]"The structure of cat muscle pyruvate kinase."
Muirhead H., Clayden D.A., Barford D., Lorimer C.G., Fothergill-Gilmore L.A., Schiltz E., Schmitt W.
EMBO J. 5:475-481(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-531, ACETYLATION AT SER-2.
[2]"Hydroxylamine cleavage of cat skeletal-muscle pyruvate kinase: separation of the fragments and N-terminal sequence analysis."
McAleese S.M., Hoar C.G., Dunbar B., Fothergill-Gilmore L.A.
Biochem. Soc. Trans. 10:444-445(1982)
Cited for: PROTEIN SEQUENCE OF 200-236.
[3]"A comparison of the structure and activity of cat and trout muscle pyruvate kinases."
Harkins R.N., Nocton J.C., Russell M.P., Fothergill-Gilmore L.A., Muirhead H.
Eur. J. Biochem. 136:341-346(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 314-330.
[4]"Crystal structure of cat muscle pyruvate kinase at a resolution of 2.6 A."
Stuart D.I., Levine M., Muirhead H., Stammers D.K.
J. Mol. Biol. 134:109-142(1979) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
[5]"Three-dimensional structure of cat muscle pyruvate kinase at 3.1-A resolution."
Stammers D.K., Muirhead H.
J. Mol. Biol. 112:309-316(1977) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS).
[6]"Three-dimensional structure of cat muscle pyruvate kinase at 6-A resolution."
Stammers D.K., Muirhead H.
J. Mol. Biol. 95:213-225(1975) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (6.0 ANGSTROMS).
[7]"Refined three-dimensional structure of cat-muscle (M1) pyruvate kinase at a resolution of 2.6 A."
Allen S.C., Muirhead H.
Acta Crystallogr. D 52:499-504(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).

Cross-references

Sequence databases

PIRA25091.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1PKMX-ray2.60A2-531[»]
ProteinModelPortalP11979.
SMRP11979. Positions 13-531.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9685.ENSFCAP00000000606.

Proteomic databases

PRIDEP11979.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

eggNOGCOG0469.
HOGENOMHOG000021559.
HOVERGENHBG000941.
OrthoDBEOG78M01Q.
TreeFamTF300390.

Enzyme and pathway databases

UniPathwayUPA00109; UER00188.

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

EvolutionaryTraceP11979.

Entry information

Entry nameKPYM_FELCA
AccessionPrimary (citable) accession number: P11979
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: March 19, 2014
This is version 136 of the entry and version 2 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways