Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P52480 (KPYM_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 148. 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·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:Pk3, Pkm2, Pykm
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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 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. 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.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity.

Tissue specificity

Embryonic stem cells and embryonal carcinoma cells. Ref.8

Post-translational modification

ISGylated. Ref.7

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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

P266633EBI-647785,EBI-6857429From a different organism.
Pou5f1P202636EBI-647785,EBI-1606219

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform M2 (identifier: P52480-1)

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 M1 (identifier: P52480-2)

Also known as: PKM2;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 531530Pyruvate kinase PKM
PRO_0000112089

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
Site4331Crucial for phosphotyrosine binding By similarity

Amino acid modifications

Modified residue371Phosphoserine By similarity
Modified residue621N6-acetyllysine Ref.10
Modified residue661N6-succinyllysine Ref.10
Modified residue891N6-acetyllysine By similarity
Modified residue1051Phosphotyrosine Ref.9
Modified residue1481Phosphotyrosine Ref.9
Modified residue1661N6-acetyllysine; alternate Ref.10
Modified residue1661N6-succinyllysine; alternate Ref.10
Modified residue1751Phosphotyrosine By similarity
Modified residue1951Phosphothreonine By similarity
Modified residue2661N6-acetyllysine By similarity
Modified residue2701N6-acetyllysine Ref.10
Modified residue3051N6-acetyllysine By similarity
Modified residue3221N6-acetyllysine; alternate Ref.10
Modified residue3221N6-succinyllysine; alternate Ref.10
Modified residue40314-hydroxyproline By similarity
Modified residue40814-hydroxyproline By similarity
Modified residue4331N6-acetyllysine By similarity
Modified residue4751N6-acetyllysine Ref.10
Modified residue4981N6-succinyllysine Ref.10

Natural variations

Alternative sequence389 – 43345IYHLQ…IVLTK → MFHRLLFEELVRASSHSTDL MEAMAMGSVEASYKCLAAAL IVLTE in isoform M1.
VSP_025057

Experimental info

Sequence conflict81A → V in CAA65761. Ref.2
Sequence conflict1211T → A in BAE30642. Ref.3
Sequence conflict1211T → A in BAE32031. Ref.3
Sequence conflict1581W → R in BAA07457. Ref.1
Sequence conflict1661K → E in BAE42098. Ref.3
Sequence conflict1701V → L in BAE30642. Ref.3
Sequence conflict1701V → L in BAE32031. Ref.3
Sequence conflict1771D → G in BAE42199. Ref.3
Sequence conflict2301K → R in BAE30642. Ref.3
Sequence conflict2301K → R in BAE32031. Ref.3
Sequence conflict2991I → T in BAA07457. Ref.1
Sequence conflict3091A → S in BAA07457. Ref.1
Sequence conflict3271A → S in BAA07457. Ref.1
Sequence conflict3271A → S in CAA65761. Ref.2
Sequence conflict3331S → I in BAA07457. Ref.1
Sequence conflict3331S → I in CAA65761. Ref.2
Sequence conflict4851D → N in BAE33055. Ref.3
Sequence conflict4851D → N in BAE42192. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform M2 (PKM1) [UniParc].

Last modified May 1, 2007. Version 4.
Checksum: 34CBBC01BC0C047D

FASTA53157,845
        10         20         30         40         50         60 
MPKPHSEAGT AFIQTQQLHA AMADTFLEHM CRLDIDSAPI TARNTGIICT IGPASRSVEM 

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

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

       190        200        210        220        230        240 
ISLQVKEKGA DFLVTEVENG 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 IAREAEAAIY HLQLFEELRR LAPITSDPTE AAAVGAVEAS 

       430        440        450        460        470        480 
FKCCSGAIIV LTKSGRSAHQ VARYRPRAPI IAVTRNPQTA RQAHLYRGIF PVLCKDAVLN 

       490        500        510        520        530 
AWAEDVDLRV NLAMDVGKAR GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P 

« Hide

Isoform M1 (PKM2) [UniParc].

Checksum: D0D163786CC6D4A6
Show »

FASTA53157,985

References

« Hide 'large scale' references
[1]"Molecular cloning of the complementary DNA for the mouse pyruvate kinase M-2 gene whose expression is dependent upon cell differentiation."
Izumi S., Manabe A., Tomoyasu A., Kihara-Negishi F., Ariga H.
Biochim. Biophys. Acta 1267:135-138(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M2).
[2]"Gene expression of mouse M1 and M2 pyruvate kinase isoenzymes correlates with differential poly(A) tract extension of their mRNAs during the development of spermatogenesis."
de Luis O., del Mazo J.
Biochim. Biophys. Acta 1396:294-305(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M2).
Strain: Swiss.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM M2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-395 (ISOFORM M1).
Strain: C57BL/6J and NOD.
Tissue: Bone marrow, Kidney and Muellerian duct.
[4]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM M2).
Strain: C57BL/6 and FVB/N.
Tissue: Brain and Mammary tumor.
[6]Lubec G., Kang S.U., Klug S., Yang J.W., Zigmond M., Sunyer B., Chen W.-Q.
Submitted (JAN-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 33-56; 67-89; 93-115; 126-136; 142-162; 167-224; 231-246; 248-255; 279-305; 320-336; 343-399; 401-433; 468-498 AND 506-526, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: C57BL/6 and OF1.
Tissue: Brain and Hippocampus.
[7]"Proteomic identification of proteins conjugated to ISG15 in mouse and human cells."
Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J., Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.
Biochem. Biophys. Res. Commun. 336:496-506(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: ISGYLATION.
[8]"Pyruvate kinase isozyme type M2 (PKM2) interacts and cooperates with Oct-4 in regulating transcription."
Lee J., Kim H.K., Han Y.-M., Kim J.
Int. J. Biochem. Cell Biol. 40:1043-1054(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[9]"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain."
Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.
J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105 AND TYR-148, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Brain.
[10]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-62; LYS-166; LYS-270; LYS-322 AND LYS-475, SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-66; LYS-166; LYS-322 AND LYS-498, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D38379 mRNA. Translation: BAA07457.1.
X97047 mRNA. Translation: CAA65761.1.
AK002341 mRNA. Translation: BAB22025.1.
AK135397 mRNA. Translation: BAE22519.1.
AK151724 mRNA. Translation: BAE30642.1.
AK153483 mRNA. Translation: BAE32031.1.
AK155110 mRNA. Translation: BAE33055.1.
AK155655 mRNA. Translation: BAE33370.1.
AK170892 mRNA. Translation: BAE42098.1.
AK168943 mRNA. Translation: BAE40751.1.
AK171023 mRNA. Translation: BAE42192.1.
AK171033 mRNA. Translation: BAE42199.1.
AC160637 Genomic DNA. No translation available.
BC016619 mRNA. Translation: AAH16619.1.
BC094663 mRNA. Translation: AAH94663.1.
PIRS55921.
RefSeqNP_001240812.1. NM_001253883.1.
NP_035229.2. NM_011099.3.
XP_006510918.1. XM_006510855.1.
UniGeneMm.326167.
Mm.488724.

3D structure databases

ProteinModelPortalP52480.
SMRP52480. Positions 13-531.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202191. 14 interactions.
IntActP52480. 16 interactions.
MINTMINT-1850796.

PTM databases

PhosphoSiteP52480.

2D gel databases

REPRODUCTION-2DPAGEIPI00407130.
P52480.
SWISS-2DPAGEP52480.

Proteomic databases

PaxDbP52480.
PRIDEP52480.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000034834; ENSMUSP00000034834; ENSMUSG00000032294. [P52480-1]
ENSMUST00000163694; ENSMUSP00000128770; ENSMUSG00000032294. [P52480-2]
GeneID18746.
KEGGmmu:18746.
UCSCuc009pyf.2. mouse. [P52480-1]
uc009pyh.2. mouse. [P52480-2]

Organism-specific databases

CTD5315.
MGIMGI:97591. Pkm.

Phylogenomic databases

eggNOGCOG0469.
GeneTreeENSGT00390000008859.
HOVERGENHBG000941.
InParanoidP52480.
KOK00873.
OMAHGTRIAN.
OrthoDBEOG78M01Q.
PhylomeDBP52480.
TreeFamTF300390.

Enzyme and pathway databases

SABIO-RKP52480.
UniPathwayUPA00109; UER00188.

Gene expression databases

BgeeP52480.
CleanExMM_PKM2.
GenevestigatorP52480.

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

ChiTaRSPKM2. mouse.
NextBio294905.
PROP52480.
SOURCESearch...

Entry information

Entry nameKPYM_MOUSE
AccessionPrimary (citable) accession number: P52480
Secondary accession number(s): Q3TBV8 expand/collapse secondary AC list , Q3TBW5, Q3TC59, Q3U1X3, Q3U5P6, Q4VC20, Q64484, Q91YI8, Q9CWB1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 1, 2007
Last modified: April 16, 2014
This is version 148 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

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot