Pyruvate kinase isozymes M1/M2 - Homo sapiens (Human)

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

Alternative products

Sequence annotation (Features)

Sequences

References

Web resources

Cross-references

Entry information

Relevant documents

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

Alternative products

Sequence annotation (Features)

Sequences

References

Web resources

Cross-references

Entry information

Relevant documents

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequence databases

3D structure databases

Protein-protein interaction databases

2-D gel databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

With

Entry

#Exp.

IntAct

Notes

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequence databases

3D structure databases

Protein-protein interaction databases

2-D gel databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Protein names

Recommended name:
    Pyruvate kinase isozymes M1/M2
    EC=2.7.1.40
Alternative name(s):
    Pyruvate kinase muscle isozyme
    Pyruvate kinase 2/3
    Cytosolic thyroid hormone-binding protein
      Short name=CTHBP
    THBP1
    p58
    Tumor M2-PK

Gene names

Name:	PKM2
Synonyms:	PK2, PK3, PKM

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Sequence length	531 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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Function	Glycolytic enzyme that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. Stimulates POU5F1-mediated transcriptional activation. Plays a general role in caspase independent cell death of tumor cells. The ratio betwween the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production. The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival. Ref.20 Ref.25
Catalytic activity	ATP + pyruvate = ADP + phosphoenolpyruvate. Ref.12
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). The activity of the tetrameric form is inhibited by PML. Ref.12 Ref.2 Ref.24 Ref.34
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. The tetrameric form has high affinity for the substrate and is associated within the glycolytic enzyme complex. Exists in a nearly inactive dimeric form in tumor cells and the dimeric form has less affinity for the substrate. Binding to certain oncoproteins such as HPV-16 E7 oncoprotein can trigger dimerization. FBP stimulates the formation of tetramers from dimers. Interacts with HERC1, POU5F1 and PML. Ref.25 Ref.12 Ref.2 Ref.24 Ref.16
Subcellular location	Cytoplasm. Nucleus. Note: Translocates to the nucleus in response to different apoptotic stimuli. Nuclear translocation is sufficient to induce cell death that is caspase independent, isoform-specific and independent of its enzymatic actvity. Ref.20 Ref.25 Ref.24
Tissue specificity	Specifically expressed in proliferating cells, such as embryonic stem cells, embryonic carcinoma cells, as well as cancer cells. Ref.25
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.17 Ref.18 Ref.19 Ref.21 Ref.22 Ref.23 Ref.26 Ref.27 Ref.28 Ref.30 Ref.31 Ref.32
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 as well as in most cancer cells.
Sequence similarities	Belongs to the pyruvate kinase family.
Biophysicochemical properties	Kinetic parameters: K_M=2.7 mM for phosphoenolpyruvate (at 32 degrees Celsius, pH 8.0) K_M=0.17 mM for phosphoenolpyruvate (in the presence of 2mM FBP, at 32 degrees Celsius, pH 8.0) K_M=0.34 mM for ADP (at 32 degrees Celsius, pH 8.0) K_M=0.24 mM for ADP (in the presence of 2mM FBP, at 32 degrees Celsius, pH 8.0) K_M=0.13 mM for phosphoenolpyruvate (in the presence of 2mM FBP, at 25 degrees Celsius) K_M=0.63 mM for ADP (in the presence of 2mM FBP, at 25 degrees Celsius) pH dependence: Optimum pH for T3 binding is 6.0-6.5. Increase in pH causes T3 binding to drop, does not bind T3 above pH 9.0 or below pH 5.0.

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Keywords
Biological process	Glycolysis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Potassium Pyruvate
Molecular function	Kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Allosteric enzyme Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	glycolysis Non-traceable author statement. Source: UniProtKB programmed cell death Ref.20 Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Ref.2 Ref.4 Non-traceable author statement. Source: UniProtKB nucleus Ref.20 Ref.25 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW potassium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.24 Ref.25 Inferred from physical interaction. Source: UniProtKB pyruvate kinase activity Ref.1 Ref.2 Ref.4 Traceable author statement. Source: UniProtKB
Complete GO annotation...

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With	Entry	#Exp.	IntAct
ARRB1	P49407	1	EBI-353408,EBI-743313
ARRB2	P32121	1	EBI-353408,EBI-714559
EXOSC5	Q9NQT4	1	EBI-353408,EBI-371876
NDRG1	Q92597	1	EBI-353408,EBI-716486
RAF1	P04049	3	EBI-353408,EBI-365996

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Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Initiator methionine

1

Removed Ref.12 Ref.11 Ref.13

Chain

2 – 531

530

Pyruvate kinase isozymes M1/M2

PRO_0000112088

Region

307 – 531

225

Interaction with POU5F1

Region

389 – 433

45

Intersubunit contact

Region

432 – 437

6

D-fructose 1,6-bisphosphate binding; part of allosteric site

Region

514 – 521

8

D-fructose 1,6-bisphosphate binding; part of allosteric site

Metal binding

75

1

Potassium By similarity

Metal binding

77

1

Potassium By similarity

Metal binding

113

1

Potassium

Metal binding

114

1

Potassium

Metal binding

272

1

Magnesium

Metal binding

296

1

Magnesium

Binding site

73

1

Substrate By similarity

Binding site

295

1

Substrate; via amide nitrogen By similarity

Binding site

296

1

Substrate; via amide nitrogen By similarity

Binding site

328

1

Substrate By similarity

Binding site

482

1

D-fructose 1,6-bisphosphate; part of allosteric site

Binding site

489

1

D-fructose 1,6-bisphosphate; part of allosteric site

Site

270

1

Transition state stabilizer

Modified residue

2

1

N-acetylserine Ref.11

Modified residue

37

1

Phosphoserine Ref.18 Ref.19 Ref.21 Ref.23 Ref.26 Ref.27 Ref.28 Ref.30 Ref.32

Modified residue

45

1

Phosphothreonine Ref.21

Modified residue

62

1

N6-acetyllysine Ref.33

Modified residue

83

1

Phosphotyrosine Ref.17

Modified residue

89

1

N6-acetyllysine Ref.33

Modified residue

105

1

Phosphotyrosine Ref.17 Ref.31

Modified residue

148

1

Phosphotyrosine Ref.32

Modified residue

166

1

N6-acetyllysine Ref.33

Modified residue

175

1

Phosphotyrosine Ref.32

Modified residue

195

1

Phosphothreonine Ref.32

Modified residue

266

1

N6-acetyllysine Ref.33

Modified residue

328

1

Phosphothreonine Ref.22

Modified residue

390

1

Phosphotyrosine Ref.17

Modified residue

433

1

N6-acetyllysine Ref.33

Alternative sequence

389 – 433

45

IYHLQ…IVLTK → MFHRKLFEELVRASSHSTDL MEAMAMGSVEASYKCLAAAL IVLTE in isoform M1.

VSP_011101

Natural variant

204

1

G → V: dbSNP rs17853396. Ref.10

VAR_033067

Sequence conflict

7

1

E → Q in AAH12811. Ref.10

Sequence conflict

54

1

A → T in BAG52542. Ref.5

Sequence conflict

103

1

I → Y in AAA36672. Ref.2

Sequence conflict

132

1

V → L in AAA36672. Ref.2

Sequence conflict

187

1

Q → R in BAD96647. Ref.6

Sequence conflict

252

1

H → R in BAD96647. Ref.6

Sequence conflict

339

1

R → P in CAA39849. Ref.4

Sequence conflict

349

1

A → V in BAG52542. Ref.5

Sequence conflict

379

1

H → N in AAA36449. Ref.1

Sequence conflict

507

1

D → H in AAH12811. Ref.10

1

.

531

Helix Strand Turn

Details...

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Sequence		Length	Mass (Da)
Isoform M2 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: AA94D7818ED6BBAD Show »	FASTA	531	57,937
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 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 IAREAEAAIY HLQLFEELRR LAPITSDPTE ATAVGAVEAS 430 440 450 460 470 480 FKCCSGAIIV LTKSGRSAHQ VARYRPRAPI IAVTRNPQTA RQAHLYRGIF PVLCKDPVQE 490 500 510 520 530 AWAEDVDLRV NFAMNVGKAR GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P « Hide
Isoform M1 [UniParc] [UniParc]. Checksum: AB9B5B2308D26B79 Show »	FASTA	531	58,062
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 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 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

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	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human M2-type pyruvate kinase: cDNA cloning, chromosomal assignment and expression in hepatoma." Tani K., Yoshida M.C., Satoh H., Mitamura K., Noguchi T., Tanaka T., Fujii H., Miwa S. Gene 73:509-516(1988) [PubMed: 2854097] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M2). Tissue: Liver.
[2]	"Cytosolic thyroid hormone-binding protein is a monomer of pyruvate kinase." Kato H., Fukuda T., Parkison C., McPhie P., Cheng S.-Y. Proc. Natl. Acad. Sci. U.S.A. 86:7861-7865(1989) [PubMed: 2813362] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M2), PROTEIN SEQUENCE OF 70-98, SUBUNIT, ENZYME REGULATION.
[3]	Erratum Kato H., Fukuda T., Parkison C., McPhie P., Cheng S.-Y. Proc. Natl. Acad. Sci. U.S.A. 87:1625-1625(1990)
[4]	"Isolation and characterization of the human pyruvate kinase M gene." Takenaka M., Noguchi T., Sadahiro S., Hirai H., Yamada K., Matsuda T., Imai E., Tanaka T. Eur. J. Biochem. 198:101-106(1991) [PubMed: 2040271] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM M1). Tissue: Astrocyte and Fetal brain.
[6]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM M2). Tissue: Kidney.
[7]	NIEHS SNPs program Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. Nusbaum C. Nature 440:671-675(2006) [PubMed: 16572171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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), VARIANT VAL-204. Tissue: Kidney, Lung carcinoma, Ovary, Retina and Rhabdomyosarcoma.
[11]	Bienvenut W.V. Unpublished observations (JUL-2005) Cited for: PROTEIN SEQUENCE OF 2-43; 57-73; 93-115; 126-135; 167-186; 231-246; 271-311; 401-422; 448-455 AND 490-498, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[12]	"An in vitro novel mechanism of regulating the activity of pyruvate kinase M2 by thyroid hormone and fructose 1, 6-bisphosphate." Ashizawa K., McPhie P., Lin K.-H., Cheng S.-Y. Biochemistry 30:7105-7111(1991) [PubMed: 1854723] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-18, CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, INTERACTION WITH THYROID HORMONE.
[13]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-32. Tissue: Platelet.
[14]	Lubec G., Vishwanath V. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 74-89, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[15]	"Using the yeast two-hybrid system to identify human epithelial cell proteins that bind gonococcal Opa proteins: intracellular gonococci bind pyruvate kinase via their Opa proteins and require host pyruvate for growth." Williams J.M., Chen G.-C., Zhu L., Rest R.F. Mol. Microbiol. 27:171-186(1998) [PubMed: 9466265] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 368-531 (ISOFORM M2).
[16]	"Interaction between HERC1 and M2-type pyruvate kinase." Garcia-Gonzalo F.R., Cruz C., Munoz P., Mazurek S., Eigenbrodt E., Ventura F., Bartrons R., Rosa J.L. FEBS Lett. 539:78-84(2003) [PubMed: 12650930] [Abstract] Cited for: INTERACTION WITH HERC1.
[17]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-83; TYR-105 AND TYR-390, MASS SPECTROMETRY.
[18]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, MASS SPECTROMETRY. Tissue: Epithelium.
[19]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, MASS SPECTROMETRY. Tissue: Epithelium.
[20]	"Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death." Stetak A., Veress R., Ovadi J., Csermely P., Keri G., Ullrich A. Cancer Res. 67:1602-1608(2007) [PubMed: 17308100] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[21]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37 AND THR-45, MASS SPECTROMETRY.
[22]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-328, MASS SPECTROMETRY.
[23]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, MASS SPECTROMETRY.
[24]	"Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML tumor suppressor protein." Shimada N., Shinagawa T., Ishii S. Genes Cells 13:245-254(2008) [PubMed: 18298799] [Abstract] Cited for: INTERACTION WITH PML, ENZYME REGULATION, SUBUNIT, SUBCELLULAR LOCATION.
[25]	"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: INTERACTION WITH POU5F1, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[26]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, MASS SPECTROMETRY. Tissue: Platelet.
[27]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, MASS SPECTROMETRY.
[28]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, MASS SPECTROMETRY.
[29]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[30]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, MASS SPECTROMETRY.
[31]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[32]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37; TYR-148; TYR-175 AND THR-195, MASS SPECTROMETRY. Tissue: T-cell.
[33]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-62; LYS-89; LYS-166; LYS-266 AND LYS-433, MASS SPECTROMETRY.
[34]	"Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis." Dombrauckas J.D., Santarsiero B.D., Mesecar A.D. Biochemistry 44:9417-9429(2005) [PubMed: 15996096] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.82 ANGSTROMS) OF ISOFORM M2 IN COMPLEX WITH OXALATE AND FBP, ACTIVE SITE, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
[35]	"Structure of human muscle pyruvate kinase (pkm2)." Structural genomics consortium (SGC) Submitted (MAY-2005) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
+	Additional computationally mapped references.

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Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Wikipedia

Pyruvate kinase entry

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EMBL
GenBank
DDBJ

M23725 mRNA. Translation: AAA36449.1.
M26252 mRNA. Translation: AAA36672.1.
X56494 Genomic DNA. Translation: CAA39849.1.
AK092369 mRNA. Translation: BAG52542.1.
AK222927 mRNA. Translation: BAD96647.1.
AK294315 mRNA. Translation: BAG57589.1. Different initiation.
AK312253 mRNA. Translation: BAG35185.1.
AY352517 Genomic DNA. Translation: AAQ15274.1.
AC020779 Genomic DNA. No translation available.
CH471082 Genomic DNA. Translation: EAW77884.1.
CH471082 Genomic DNA. Translation: EAW77888.1.
BC000481 mRNA. Translation: AAH00481.3.
BC007640 mRNA. Translation: AAH07640.1.
BC007952 mRNA. Translation: AAH07952.3.
BC012811 mRNA. Translation: AAH12811.3.
BC035198 mRNA. Translation: AAH35198.1.
AF025439 mRNA. Translation: AAC39559.1.

IPI

IPI00220644.
IPI00479186.

PIR

S30038.
S64635.

RefSeq

NP_002645.3.
NP_872270.1.
NP_872271.1.

UniGene

Hs.534770

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1T5A	X-ray	2.80	A/B/C/D	1-531	[»]
1ZJH	X-ray	2.20	A	3-530	[»]
3BJF	X-ray	2.03	A/B/C/D	14-531	[»]
3BJT	X-ray	2.50	A/B/C/D	2-531	[»]
3G2G	X-ray	2.00	A/B/C/D	1-531	[»]
3GQY	X-ray	1.85	A/B/C/D	1-531	[»]
3GR4	X-ray	1.60	A/B/C/D	1-531	[»]
3H6O	X-ray	2.00	A/B/C/D	1-531	[»]

ModBase

Search...

IntAct

P14618. 10 interactions.

STRING

P14618.

Aarhus/Ghent-2DPAGE

3509. NEPHGE.

DOSAC-COBS-2DPAGE

P14618.

OGP

P14618.

REPRODUCTION-2DPAGE

IPI00220644.
IPI00479186.

PRIDE

P14618.

Ensembl

ENST00000335181; ENSP00000334983; ENSG00000067225; Homo sapiens. [Genome view]

GeneID

5315.

KEGG

hsa:5315.

UCSC

uc002atv.1. human.
uc002aty.1. human.

CTD

5315.

GeneCards

GC15M070278.
GC15M070279.

H-InvDB

HIX0012404.
HIX0077639.
HIX0079720.

HGNC

HGNC:9021. PKM2.

HPA

CAB019421.

MIM

179050. gene.

PharmGKB

PA33353.

GenAtlas

Search...

eggNOG

prNOG12218.

HOVERGEN

P14618.

InParanoid

P14618.

OMA

TMENAVE.

PhylomeDB

P14618.

BRENDA

2.7.1.40. 247.

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.

Reactome

REACT_1505. Integration of energy metabolism.
REACT_15380. Diabetes pathways.
REACT_474. Metabolism of carbohydrates.

ArrayExpress

P14618.

Bgee

P14618.

CleanEx

HS_PKM2.

Genevestigator

P14618.

GermOnline

ENSG00000067225. Homo sapiens.

InterPro

IPR001697. Pyr_Knase.
IPR015813. Pyrv/PenolPyrv_Kinase_cat.
IPR015794. Pyrv_Knase_a/b.
IPR018209. Pyrv_Knase_AS.
IPR011037. Pyrv_Knase_b-brl-like.
IPR015793. Pyrv_Knase_brl.
IPR015795. Pyrv_Knase_C-like.
[Graphical view]

Gene3D

G3DSA:3.20.20.60. Pyrv/PenolPyrv_Kinase_cat. 1 hit.
G3DSA:3.40.1380.20. Pyrv_Knase_a/b. 1 hit.

PANTHER

PTHR11817. Pyruvate_kinase. 1 hit.

Pfam

PF00224. PK. 1 hit.
PF02887. PK_C. 1 hit.
[Graphical view]

PRINTS

PR01050. PYRUVTKNASE.

TIGRFAMs

TIGR01064. pyruv_kin. 1 hit.

PROSITE

PS00110. PYRUVATE_KINASE. 1 hit.
[Graphical view]

ProtoNet

Search...

DrugBank

DB00119. Pyruvic acid.

NextBio

20554.

SOURCE

Search...

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Entry name

KPYM_HUMAN

Accession

Primary (citable) accession number: P14618
Secondary accession number(s): A6NFK3

Q9UPF2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 144 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform M2 (identifier: P14618-1)

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: P14618-2)

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