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Reviewed, UniProtKB/Swiss-Prot P52480 (KPYM_MOUSE)

Last modified November 3, 2009. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Pyruvate kinase isozymes M1/M2
    EC=2.7.1.40
Alternative name(s):
    Pyruvate kinase muscle isozyme
Gene names
Name: Pkm2
Synonyms: Pk3, Pykm
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

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

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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-biphosphate (FBP). Inhibited by oxalate and 3,3',5-triiodo-L-thyronine (T3) 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 By similarity.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity.

Tissue specificity

Embryonic stem cells and embryonal carcinoma cells. Ref.7

Post-translational modification

Phosphorylated upon DNA damage, probably by ATM or ATR By similarity.

Miscellaneous

There are 4 isozymes of pyruvate kinase in mammals: L, R, M1 and M2. 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.

Sequence similarities

Belongs to the pyruvate kinase family.

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

Pou5f1P202634EBI-647785,EBI-1606219

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Alternative products

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

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)

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

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 531530Pyruvate kinase isozymes M1/M2
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

Active site2701 By similarity
Metal binding1131Potassium By similarity
Metal binding1141Potassium By similarity
Metal binding2721Magnesium By similarity
Metal binding2961Magnesium 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

Amino acid modifications

Modified residue371Phosphoserine By similarity
Modified residue451Phosphothreonine By similarity
Modified residue621N6-acetyllysine By similarity
Modified residue831Phosphotyrosine By similarity
Modified residue891N6-acetyllysine By similarity
Modified residue1051Phosphotyrosine Ref.8
Modified residue1481Phosphotyrosine Ref.8
Modified residue1661N6-acetyllysine By similarity
Modified residue2661N6-acetyllysine By similarity
Modified residue3281Phosphothreonine By similarity
Modified residue3901Phosphotyrosine By similarity
Modified residue4331N6-acetyllysine By similarity

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

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Sequences

Sequence LengthMass (Da)Tools
Isoform M2 [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.

Checksum: D0D163786CC6D4A6
Show »

FASTA53157,985

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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: 7612666] [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: 9545585] [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: 16141072] [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: 19468303] [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: 15489334] [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, MASS SPECTROMETRY.
Strain: C57BL/6 and OF1.
Tissue: Brain and Hippocampus.
[7]"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: 18191611] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"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: 18034455] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105 AND TYR-148, MASS SPECTROMETRY.
Tissue: Brain.
+Additional computationally mapped references.

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Cross-references

Sequence databases

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.
IPIIPI00407130.
IPI00845840.
PIRS55921.
RefSeqNP_035229.2.
UniGeneMm.326167

3D structure databases

HSSPHSSP built from PDB template 1PKN based on UniProtKB P11974.
SMRP52480. Positions 11-531.
ModBaseSearch...

Protein-protein interaction databases

IntActP52480. 4 interactions.
STRINGP52480.

PTM databases

PhosphoSiteP52480.

2-D gel databases

SWISS-2DPAGEP52480.
PMMA-2DPAGEP52480.
REPRODUCTION-2DPAGEP52480.

Proteomic databases

PRIDEP52480.

Genome annotation databases

EnsemblENSMUST00000034834; ENSMUSP00000034834; ENSMUSG00000032294; Mus musculus. [Genome view]
GeneID18746.
KEGGmmu:18746.
UCSCuc009pyf.1. mouse.
uc009pyi.1. mouse.

Organism-specific databases

CTD18746.
MGIMGI:97591. Pkm2.

Phylogenomic databases

HOVERGENP52480.
OMATMENAVE.

Enzyme and pathway databases

BRENDA2.7.1.40. 244.

Gene expression databases

ArrayExpressP52480.
BgeeP52480.
CleanExMM_PKM2.
GenevestigatorP52480.
GermOnlineENSMUSG00000032294. Mus musculus.

Family and domain databases

InterProIPR001697. Pyr_Knase.
IPR015813. Pyrv/PenolPyrv_Kinase_cat.
IPR015794. Pyrv_Knase_a/b.
IPR018209. Pyrv_Knase_AS.
IPR015793. Pyrv_Knase_brl.
[Graphical view]
Gene3DG3DSA:3.20.20.60. Pyrv/PenolPyrv_Kinase_cat. 1 hit.
G3DSA:3.40.1380.20. Pyrv_Knase_a/b. 1 hit.
PANTHERPTHR11817. Pyruvate_kinase. 1 hit.
PfamPF00224. PK. 1 hit.
PF02887. PK_C. 1 hit.
[Graphical view]
PRINTSPR01050. PYRUVTKNASE.
ProDomPD001009. Pyruvate_kinase. 2 hits.
[Graphical view] [Entries sharing at least one domain]
TIGRFAMsTIGR01064. pyruv_kin. 1 hit.
PROSITEPS00110. PYRUVATE_KINASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio294905.
SOURCESearch...

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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: November 3, 2009
This is version 104 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

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

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents