Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Pyruvate kinase isozymes M1/M2  

UniProtKB / Swiss-Prot ID :  KPYM_HUMAN

Gene Name (Synonyms) : 
PKM2, OIP3, PK2, PK3, PKM  

Species :  Homo sapiens (Human). 

Subcellular Localization :  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. 

Protein 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. 

Protein Sequence MSKPHSEAGTAFIQTQQLHAAMADTFLEHMCRLDIDSPPITARNTGIICTIGPASRSVETLKEMIKSGMN...
Predicted Secondary Structure CCCCCCHHCCEEEEECCHHHCCHHHHHHHHHCCCCCCCCCCCCCCEEEEEECCCCCCHHHHHHHHHCCCC...
Protein Variant
LocationDescription
204G -> V (in dbSNP:rs17853396). VAR_033067
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
2N-acetylserine---MSKPHS
---CCCCCC
55.69HPRD
Link-
2N-acetylserine.---MSKPHS
---CCCCCC
55.69UniProtKB
Link-
37PhosphoserineLDIDSPPIT
CCCCCCCCC
32.67HPRD
Link
37PhosphoserineLDIDSPPIT
CCCCCCCCC
32.67PhosphoELM
Link
37PhosphoserineLDIDSPPIT
CCCCCCCCC
32.67Phosphositeplus
Link
37PhosphoserineLDIDSPPIT
CCCCCCCCC
32.67SysPTM
Link
37PhosphoserineLDIDSPPIT
CCCCCCCCC
32.67SysPTM
Link
37Phosphoserine.LDIDSPPIT
CCCCCCCCC
32.67UniProtKB
Link
45PhosphothreonineTARNTGIIC
CCCCCEEEE
24.97HPRD
Link
45PhosphothreonineTARNTGIIC
CCCCCEEEE
24.97PhosphoELM
Link
45PhosphothreonineTARNTGIIC
CCCCCEEEE
24.97Phosphositeplus
Link
45PhosphothreonineTARNTGIIC
CCCCCEEEE
24.97SysPTM
Link
45Phosphothreonine.TARNTGIIC
CCCCCEEEE
24.97UniProtKB
Link
49S-nitrosocysteineTGIICTIGP
CEEEEEECC
1.83HPRD
Link
57PhosphoserinePASRSVETL
CCCCCHHHH
23.08HPRD
Link
57PhosphoserinePASRSVETL
CCCCCHHHH
23.08Phosphositeplus
Link
62Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)VETLKEMIK
HHHHHHHHH
53.29Phosphositeplus
Link
62N6-acetyllysineVETLKEMIK
HHHHHHHHH
53.29HPRD
Link
62N6-acetyllysineVETLKEMIK
HHHHHHHHH
53.29Phosphositeplus
Link
62N6-acetyllysine.VETLKEMIK
HHHHHHHHH
53.29UniProtKB
Link
66Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)KEMIKSGMN
HHHHHCCCC
39.38Phosphositeplus
Link
83PhosphotyrosineGTHEYHAET
CCHHHHHHH
9.95PhosphoELM
Link
83PhosphotyrosineGTHEYHAET
CCHHHHHHH
9.95Phosphositeplus
Link
83Phosphotyrosine.GTHEYHAET
CCHHHHHHH
9.95UniProtKB
Link
89Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)AETIKNVRT
HHHHHHHHH
57.73Phosphositeplus
Link
89N6-acetyllysineAETIKNVRT
HHHHHHHHH
57.73HPRD
Link
89N6-acetyllysineAETIKNVRT
HHHHHHHHH
57.73Phosphositeplus
Link
89N6-acetyllysine.AETIKNVRT
HHHHHHHHH
57.73UniProtKB
Link
105PhosphotyrosineDPILYRPVA
CCCCCCCEE
17.37HPRD
Link
105PhosphotyrosineDPILYRPVA
CCCCCCCEE
17.37PhosphoELM
Link
105PhosphotyrosineDPILYRPVA
CCCCCCCEE
17.37Phosphositeplus
Link
105Phosphotyrosine.DPILYRPVA
CCCCCCCEE
17.37UniProtKB
Link
115Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)ALDTKGPEI
EEECCCCEE
72.62Phosphositeplus
Link
125Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)TGLIKGSGT
EEEECCCCC
52.66Phosphositeplus
Link
129PhosphothreonineKGSGTAEVE
CCCCCCEEE
22.72HPRD
Link
135Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)EVELKKGAT
EEEECCCCE
35.34Phosphositeplus
Link
135N6-acetyllysineEVELKKGAT
EEEECCCCE
35.34HPRD
Link
135N6-acetyllysineEVELKKGAT
EEEECCCCE
35.34Phosphositeplus
Link
148PhosphotyrosineLDNAYMEKC
ECHHHCCCC
16.44Phosphositeplus
Link
148Phosphotyrosine.LDNAYMEKC
ECHHHCCCC
16.44UniProtKB
Link
151Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)AYMEKCDEN
HHCCCCCCC
30.38Phosphositeplus
Link
152S-nitrosocysteineYMEKCDENI
HCCCCCCCE
5.17dbSNO
Link
162Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)WLDYKNICK
EECCCCHHH
39.23Phosphositeplus
Link
166Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)KNICKVVEV
CCHHHHCCC
45.58Phosphositeplus
Link
166N6-acetyllysineKNICKVVEV
CCHHHHCCC
45.58HPRD
Link
166N6-acetyllysineKNICKVVEV
CCHHHHCCC
45.58Phosphositeplus
Link
166N6-acetyllysine.KNICKVVEV
CCHHHHCCC
45.58UniProtKB
Link
172PhosphoserineVEVGSKIYV
CCCCCEEEE
22.51HPRD
Link
172PhosphoserineVEVGSKIYV
CCCCCEEEE
22.51Phosphositeplus
Link
175PhosphotyrosineGSKIYVDDG
CCEEEEECC
11.10Phosphositeplus
Link
175Phosphotyrosine.GSKIYVDDG
CCEEEEECC
11.10UniProtKB
Link
186Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)SLQVKQKGA
EEEEEEEEC
33.07Phosphositeplus
Link
188Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)QVKQKGADF
EEEEEECCE
50.80Phosphositeplus
Link
195PhosphothreonineDFLVTEVEN
CEEEEEEEE
36.14Phosphositeplus
Link
195Phosphothreonine.DFLVTEVEN
CEEEEEEEE
36.14UniProtKB
Link
206Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)SLGSKKGVN
EECCCCCEE
52.31Phosphositeplus
Link
207Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)LGSKKGVNL
ECCCCCEEC
70.55Phosphositeplus
Link
224Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)AVSEKDIQD
CCCHHHHHH
53.26Phosphositeplus
Link
249PhosphoserineIRKASDVHE
CCCHHHHHH
43.11Phosphositeplus
Link
261Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)VLGEKGKNI
HHHHHCCCC
73.68Phosphositeplus
Link
266Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)GKNIKIISK
CCCCEEEEE
43.30Phosphositeplus
Link
266N6-acetyllysineGKNIKIISK
CCCCEEEEE
43.30HPRD
Link
266N6-acetyllysineGKNIKIISK
CCCCEEEEE
43.30Phosphositeplus
Link
266N6-acetyllysine.GKNIKIISK
CCCCEEEEE
43.30UniProtKB
Link
270Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)KIISKIENH
EEEEEECCH
43.56Phosphositeplus
Link
287PhosphoserineILEASDGIM
HHHHHCCEE
27.30HPRD
Link
287PhosphoserineILEASDGIM
HHHHHCCEE
27.30Phosphositeplus
Link
305Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)IPAEKVFLA
CCHHHHHHH
40.15Phosphositeplus
Link
305N6-acetyllysineIPAEKVFLA
CCHHHHHHH
40.15HPRD
Link
305N6-acetyllysineIPAEKVFLA
CCHHHHHHH
40.15Phosphositeplus
Link
311Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)FLAQKMMIG
HHHHHHHHH
25.48Phosphositeplus
Link
322Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)NRAGKPVIC
HHHCCCEEE
34.82Phosphositeplus
Link
328PhosphothreonineVICATQMLE
EEEEEHHHH
15.31HPRD
Link
328PhosphothreonineVICATQMLE
EEEEEHHHH
15.31PhosphoELM
Link
328PhosphothreonineVICATQMLE
EEEEEHHHH
15.31Phosphositeplus
Link
328Phosphothreonine.VICATQMLE
EEEEEHHHH
15.31UniProtKB
Link
370PhosphotyrosineAKGDYPLEA
CCCCCHHHH
20.56Phosphositeplus
Link
390PhosphotyrosineEAAIYHLQL
HHCCCHHHH
7.55HPRD
Link
390PhosphotyrosineEAAIYHLQL
HHCCCHHHH
7.55PhosphoELM
Link
390PhosphotyrosineEAAIYHLQL
HHCCCHHHH
7.55Phosphositeplus
Link
390Phosphotyrosine.EAAIYHLQL
HHCCCHHHH
7.55UniProtKB
Link
4034-hydroxyproline.RRLAPITSD
HCCCCCCCC
34.67UniProtKB
Link
405PhosphothreonineLAPITSDPT
CCCCCCCHH
26.47HPRD
Link
406PhosphoserineAPITSDPTE
CCCCCCHHH
42.17HPRD
Link
4084-hydroxyproline.ITSDPTEAT
CCCCHHHHH
31.72UniProtKB
Link
423S-nitrosocysteineASFKCCSGA
HHHHCCCCE
1.79dbSNO
Link
424S-nitrosocysteineSFKCCSGAI
HHHCCCCEE
4.30dbSNO
Link
433Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)IVLTKSGRS
EEEECCCCH
46.91Phosphositeplus
Link
433N6-acetyllysineIVLTKSGRS
EEEECCCCH
46.91HPRD
Link
433N6-acetyllysineIVLTKSGRS
EEEECCCCH
46.91Phosphositeplus
Link
433N6-acetyllysine.IVLTKSGRS
EEEECCCCH
46.91UniProtKB
Link
466PhosphotyrosineQAHLYRGIF
HHCEEECEE
9.27Phosphositeplus
Link
474S-nitrosocysteineFPVLCKDPV
EEEEECCCC
4.84dbSNO
Link
475Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)PVLCKDPVQ
EEEECCCCC
61.99Phosphositeplus
Link
498Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)MNVGKARGF
HHHHHHCCC
30.54Phosphositeplus
Link
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
NOE2_HUMANphysical interactionMINT-63322MINT16169070
RAF1_HUMANphysical interactionMINT-19324MINT12620389
HS90B_HUMANphysical interactionMINT-72647MINT16263121
NDRG1_HUMANphysical interactionEBI-1190869
intact17220478
RAF1_HUMANyeast 2-hybridHPRD:01529HPRD12620389
KPYM_HUMANin vitro
in vivo
HPRD:01529HPRD11960989
2813362
SHBG_HUMANyeast 2-hybridHPRD:01529HPRD15862967
NOE2_HUMANyeast 2-hybridHPRD:01529HPRD16169070
MRP_HUMANin vitroHPRD:01529HPRD8132675
DLDH_HUMANENSP00000334983STRING
DLDH_HUMANENSP00000334983STRING
EXOS5_HUMANENSP00000334983STRING
EXOS5_HUMANENSP00000334983STRING
ODPX_HUMANENSP00000334983STRING
ODPX_HUMANENSP00000334983STRING
TPIS_HUMANENSP00000334983STRING
TPIS_HUMANENSP00000334983STRING
ENOG_HUMANENSP00000334983STRING
ENOG_HUMANENSP00000334983STRING
RIR2B_HUMANENSP00000334983STRING
RIR2B_HUMANENSP00000334983STRING
PNPT1_HUMANENSP00000334983STRING
PNPT1_HUMANENSP00000334983STRING
KAD7_HUMANENSP00000334983STRING
KAD7_HUMANENSP00000334983STRING
ODP2_HUMANENSP00000334983STRING
ODP2_HUMANENSP00000334983STRING
ODPAT_HUMANENSP00000334983STRING
ODPAT_HUMANENSP00000334983STRING
ODPAT_HUMANENSP00000334983STRING
ODPAT_HUMANENSP00000334983STRING
ODPAT_HUMANENSP00000334983STRING
ODPAT_HUMANENSP00000334983STRING
LDHD_HUMANENSP00000334983STRING
LDHD_HUMANENSP00000334983STRING
RIR1_HUMANENSP00000334983STRING
RIR1_HUMANENSP00000334983STRING
ENTP3_HUMANENSP00000334983STRING
ENTP3_HUMANENSP00000334983STRING
RIR2_HUMANENSP00000334983STRING
RIR2_HUMANENSP00000334983STRING
ODPB_HUMANENSP00000334983STRING
ODPB_HUMANENSP00000334983STRING
CANT1_HUMANENSP00000334983STRING
CANT1_HUMANENSP00000334983STRING
KGUA_HUMANENSP00000334983STRING
KGUA_HUMANENSP00000334983STRING
PPCKC_HUMANENSP00000334983STRING
PPCKC_HUMANENSP00000334983STRING
MAOM_HUMANENSP00000334983STRING
MAOM_HUMANENSP00000334983STRING
ENOB_HUMANENSP00000334983STRING
ENOB_HUMANENSP00000334983STRING
ENTP5_HUMANENSP00000334983STRING
ENTP5_HUMANENSP00000334983STRING
ENTP8_HUMANENSP00000334983STRING
ENTP8_HUMANENSP00000334983STRING
ENTP8_HUMANENSP00000334983STRING
ENTP8_HUMANENSP00000334983STRING
AP4A_HUMANENSP00000334983STRING
AP4A_HUMANENSP00000334983STRING
ALAT2_HUMANENSP00000334983STRING
ALAT2_HUMANENSP00000334983STRING
KAD5_HUMANENSP00000334983STRING
KAD5_HUMANENSP00000334983STRING
ENTP4_HUMANENSP00000334983STRING
ENTP4_HUMANENSP00000334983STRING
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Disease Reference
Kegg disease
There are no disease associations of PTM sites.
Drug Reference
DrugBank
DB00119Pyruvic acid
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Related Literatures of Post-Translational Modification
Acetylation
ReferencePubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions.";
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.;
Science 325:834-840(2009).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-62; LYS-89; LYS-166; LYS-266AND LYS-433, AND MASS SPECTROMETRY.
Hydroxylation
ReferencePubMed
"Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1.";
Luo W., Hu H., Chang R., Zhong J., Knabel M., O'Meally R., Cole R.N.,Pandey A., Semenza G.L.;
Cell 145:732-744(2011).
Cited for: INTERACTION WITH EGLN3 AND HIF1A, SUBCELLULAR LOCATION, INDUCTION,FUNCTION, MASS SPECTROMETRY, HYDROXYLATION AT PRO-403 AND PRO-408, ANDMUTAGENESIS OF PRO-403 AND PRO-408.
Phosphorylation
ReferencePubMed
"Immunoaffinity profiling of tyrosine phosphorylation in cancercells.";
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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-83; TYR-105 AND TYR-390,AND MASS SPECTROMETRY.
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks.";
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.;
Cell 127:635-648(2006).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND MASSSPECTROMETRY.
"A probability-based approach for high-throughput proteinphosphorylation analysis and site localization.";
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
Nat. Biotechnol. 24:1285-1292(2006).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND MASSSPECTROMETRY.
"Global proteomic profiling of phosphopeptides using electron transferdissociation 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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37 AND THR-45, AND MASSSPECTROMETRY.
"ATM and ATR substrate analysis reveals extensive protein networksresponsive 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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-328, AND MASSSPECTROMETRY.
"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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND MASSSPECTROMETRY.
"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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND MASSSPECTROMETRY.
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe 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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND MASSSPECTROMETRY.
"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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND MASSSPECTROMETRY.
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach.";
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.;
Anal. Chem. 81:4493-4501(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND MASSSPECTROMETRY.
"An extensive survey of tyrosine phosphorylation revealing new sitesin 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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105, AND MASSSPECTROMETRY.
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals 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).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37; TYR-148; TYR-175 ANDTHR-195, AND MASS SPECTROMETRY.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures