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Q5NVN0 (KPYM_PONAB) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 72. 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·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
OrganismPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii) [Reference proteome]
Taxonomic identifier9601 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo

Protein attributes

Sequence length531 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript 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 By similarity.

Potassium By similarity.

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.

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 531530Pyruvate kinase PKM
PRO_0000112090

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 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

Experimental info

Sequence conflict1531D → G in CAH93166. Ref.1
Sequence conflict3291Q → R in CAH93166. Ref.1
Sequence conflict3471G → D in CAH93166. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q5NVN0 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 86BDD4AEF68B5510

FASTA53158,018
        10         20         30         40         50         60 
MSKPHSEAGT AFIQTQQLHA AMADTFLEHM CRLDIDSPPI TARNTGIICT IGPASRSVET 

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

       130        140        150        160        170        180 
TGLIKGSGTA EVELKKGATL KITLDNAYME KCDENILWLD YKNICKVVEV GSKIYVDDGL 

       190        200        210        220        230        240 
ISLQVKQKGA DFLLTEVENG 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 TRAEGSGVAN AVLDGADCIM 

       370        380        390        400        410        420 
LSGETAKGDY PLEAVRMQHL IAREAEAAMF HRKLFEELVR ASSHSTDLME AMAMGSVEAS 

       430        440        450        460        470        480 
YKCLAAALIV LTESGRSAHQ VARYRPRAPI IAVTRNPQTA RQAHLYRGIF PVLCKDPVQE 

       490        500        510        520        530 
AWAEDVDLRV NFAMNVGKAR GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P 

« Hide

References

[1]The German cDNA consortium
Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain cortex.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
CR861086 mRNA. Translation: CAH93166.1.
CR925988 mRNA. Translation: CAI29633.1.
RefSeqNP_001127083.1. NM_001133611.1.

3D structure databases

ProteinModelPortalQ5NVN0.
SMRQ5NVN0. Positions 13-531.
ModBaseSearch...
MobiDBSearch...

Proteomic databases

PRIDEQ5NVN0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100174114.
KEGGpon:100174114.

Organism-specific databases

CTD396456.

Phylogenomic databases

HOVERGENHBG000941.
KOK00873.

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...

Entry information

Entry nameKPYM_PONAB
AccessionPrimary (citable) accession number: Q5NVN0
Secondary accession number(s): Q5R500
Entry history
Integrated into UniProtKB/Swiss-Prot: January 24, 2006
Last sequence update: January 23, 2007
Last modified: March 19, 2014
This is version 72 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