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P11974 (KPYM_RABIT) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 137. 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·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·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
OrganismOryctolagus cuniculus (Rabbit) [Reference proteome]
Taxonomic identifier9986 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus

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

Isoform M2 is 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 of isoform M2 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, EGLN3 (isoform M2) HF1A, 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.

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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CKMP005632EBI-7133357,EBI-2750756

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform M1 (identifier: P11974-1)

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: P11974-2)

Also known as: PKM2;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 531530Pyruvate kinase PKM
PRO_0000112091

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 By similarity
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

Natural variations

Alternative sequence389 – 43345MFHRK…IVLTE → IYHLQLFEELRRLAPITSDP TEAAAVGAVEASFKCCSGAI IVLTK in isoform M2.
VSP_011106

Experimental info

Sequence conflict4011S → A in AAC48536. Ref.3

Secondary structure

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

Details...

Sequences

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

Last modified January 23, 2007. Version 4.
Checksum: AC0AFB579FC505E6

FASTA53158,048
        10         20         30         40         50         60 
MSKSHSEAGS AFIQTQQLHA AMADTFLEHM CRLDIDSAPI TARNTGIICT IGPASRSVET 

        70         80         90        100        110        120 
LKEMIKSGMN VARMNFSHGT HEYHAETIKN VRTATESFAS DPILYRPVAV ALDTKGPEIR 

       130        140        150        160        170        180 
TGLIKGSGTA EVELKKGATL KITLDNAYME KCDENILWLD YKNICKVVDV GSKVYVDDGL 

       190        200        210        220        230        240 
ISLQVKQKGP DFLVTEVENG GFLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV 

       250        260        270        280        290        300 
FASFIRKAAD VHEVRKILGE KGKNIKIISK IENHEGVRRF DEILEASDGI MVARGDLGIE 

       310        320        330        340        350        360 
IPAEKVFLAQ KMIIGRCNRA GKPVICATQM LESMIKKPRP TRAEGSDVAN AVLDGADCIM 

       370        380        390        400        410        420 
LSGETAKGDY PLEAVRMQHL IAREAEAAMF HRKLFEELAR SSSHSTDLME AMAMGSVEAS 

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

       490        500        510        520        530 
AWAEDVDLRV NLAMNVGKAR GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P 

« Hide

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

Checksum: 5BCA6BC40C2FCA2D
Show »

FASTA53157,905

References

[1]"Structure of rabbit muscle pyruvate kinase complexed with Mn2+, K+, and pyruvate."
Larsen T.M., Laughlin L.T., Holden H.M., Rayment I., Reed G.H.
Biochemistry 33:6301-6309(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M1), X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH MANGANESE AND PAOTASSIUM IONS AND PYRUVATE.
Tissue: Skeletal muscle.
[2]Laughlin L.T.
Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 234-235.
[3]"Effects of conserved residues on the regulation of rabbit muscle pyruvate kinase."
Cheng X., Friesen R.H.E., Lee J.C.
J. Biol. Chem. 271:6313-6321(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M1).
[4]"Interfacial communications in recombinant rabbit kidney pyruvate kinase."
Friesen R.H.E., Chin A.J., Ledman D.W., Lee J.C.
Biochemistry 37:2949-2960(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M2).
Tissue: Kidney.
[5]"Isolation and sequence determination of an active site peptide of rabbit muscle pyruvate kinase."
Bezares G., Eyzaguirre J., Hinrichs M.V., Heinrikson R.L., Reardon I., Kemp R.G., Latshaw S.P., Bazaes S.
Arch. Biochem. Biophys. 253:133-137(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 343-376.
[6]"Ligand-induced domain movement in pyruvate kinase: structure of the enzyme from rabbit muscle with Mg2+, K+, and L-phospholactate at 2.7-A resolution."
Larsen T.M., Benning M.M., Wesenberg G.E., Rayment I., Reed G.H.
Arch. Biochem. Biophys. 345:199-206(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH L-PHOSPHOLACTATE, MAGNESIUM AND POTASSIUM IONS.
Tissue: Skeletal muscle.
[7]"Structure of the bis(Mg2+)-ATP-oxalate complex of the rabbit muscle pyruvate kinase at 2.1 A resolution: ATP binding over a barrel."
Larsen T.M., Benning M.M., Rayment I., Reed G.H.
Biochemistry 37:6247-6255(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) IN COMPLEX WITH OXYLATE AND MAGNESIUM IONS.
Tissue: Skeletal muscle.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U09028 mRNA. Translation: AAB61963.1.
U44751 mRNA. Translation: AAC48536.1.
AF032389 mRNA. Translation: AAB86587.1.
PIRA28506.
A54113.
RefSeqNP_001182573.1. NM_001195644.1.
NP_001182574.1. NM_001195645.1.
UniGeneOcu.2156.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1A49X-ray2.10A/B/C/D/E/F/G/H2-531[»]
1A5UX-ray2.35A/B/C/D/E/F/G/H2-531[»]
1AQFX-ray2.70A/B/C/D/E/F/G/H2-531[»]
1F3WX-ray3.00A/B/C/D/E/F/G/H2-530[»]
1F3XX-ray2.80A/B/C/D/E/F/G/H2-530[»]
1PKNX-ray2.90A2-531[»]
2G50X-ray1.65A/B/C/D/E/F/G/H2-530[»]
3N25X-ray2.41A/B/C/D/E/F/G/H1-531[»]
ProteinModelPortalP11974.
SMRP11974. Positions 13-531.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-47514N.
IntActP11974. 1 interaction.
MINTMINT-6824949.

Chemistry

ChEMBLCHEMBL5637.

Proteomic databases

PRIDEP11974.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100008676.

Organism-specific databases

CTD5315.

Phylogenomic databases

eggNOGCOG0469.
HOGENOMHOG000021559.
HOVERGENHBG000941.

Enzyme and pathway databases

SABIO-RKP11974.
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

EvolutionaryTraceP11974.

Entry information

Entry nameKPYM_RABIT
AccessionPrimary (citable) accession number: P11974
Secondary accession number(s): O18919, Q29501
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: March 19, 2014
This is version 137 of the entry and version 4 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