UniProt Accession

 KPYM_HUMAN; P14618; A6NFK3; B2R5N8; B3KRY0; B4DFX8; B4DUU6; P14786; Q53GK4; Q96E76; Q9BWB5; Q9UCV6; Q9UPF2 

Genbank Protein ID

 M23725; M26252; X56494; AK092369; AK222927; AK294315; AK300800; AK312253; AY352517; AC020779; CH471082; CH471082; BC000481; BC007640; BC007952; BC012811; BC035198; AF025439 

Genbank Nucleotide ID

 AAA36449.1; AAA36672.1; CAA39849.1; BAG52542.1; BAD96647.1; BAG57589.1; BAG62458.1; BAG35185.1; AAQ15274.1; EAW77884.1; EAW77888.1; AAH00481.3; AAH07640.1; AAH07952.3; AAH12811.3; AAH35198.1; AAC39559.1 

Protein Name

 Pyruvate kinase PKM 

Protein Synonyms/Alias

 Cytosolic thyroid hormone-binding protein; CTHBP; Opa-interacting protein 3; OIP-3; Pyruvate kinase 2/3; Pyruvate kinase muscle isozyme; Thyroid hormone-binding protein 1; THBP1; Tumor M2-PK; p58 

Gene Name

 PKM 

Gene Synonyms/Alias

 OIP3; PK2; PK3; PKM2 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
3	*****MSKPHSEAGT	ubiquitination	[1]
62	SRSVETLKEMIKSGM	acetylation	[2, 3]
62	SRSVETLKEMIKSGM	ubiquitination	[1, 4, 5, 6, 7]
66	ETLKEMIKSGMNVAR	ubiquitination	[1, 4, 5, 6, 7]
89	EYHAETIKNVRTATE	acetylation	[2]
89	EYHAETIKNVRTATE	ubiquitination	[1, 4, 5, 6, 7]
115	VAVALDTKGPEIRTG	ubiquitination	[1, 5, 7, 8, 9]
125	EIRTGLIKGSGTAEV	ubiquitination	[1, 5, 6]
135	GTAEVELKKGATLKI	acetylation	[2]
135	GTAEVELKKGATLKI	ubiquitination	[1, 5]
136	TAEVELKKGATLKIT	ubiquitination	[1]
141	LKKGATLKITLDNAY	ubiquitination	[1]
151	LDNAYMEKCDENILW	ubiquitination	[1, 5]
162	NILWLDYKNICKVVE	ubiquitination	[1, 5]
166	LDYKNICKVVEVGSK	acetylation	[2]
166	LDYKNICKVVEVGSK	ubiquitination	[1, 5, 6]
186	GLISLQVKQKGADFL	ubiquitination	[1, 5]
188	ISLQVKQKGADFLVT	ubiquitination	[1, 5]
206	NGGSLGSKKGVNLPG	ubiquitination	[1, 4, 5, 7, 9]
207	GGSLGSKKGVNLPGA	ubiquitination	[1, 5, 6]
224	DLPAVSEKDIQDLKF	ubiquitination	[1, 5]
261	VRKVLGEKGKNIKII	ubiquitination	[5]
266	GEKGKNIKIISKIEN	acetylation	[2]
266	GEKGKNIKIISKIEN	ubiquitination	[1, 5]
270	KNIKIISKIENHEGV	ubiquitination	[1, 4, 5, 6, 7]
305	GIEIPAEKVFLAQKM	acetylation	[2, 3, 10]
305	GIEIPAEKVFLAQKM	ubiquitination	[1, 5, 6, 7, 11]
311	EKVFLAQKMMIGRCN	ubiquitination	[1, 5, 6, 7]
322	GRCNRAGKPVICATQ	ubiquitination	[1, 5, 6]
367	MLSGETAKGDYPLEA	ubiquitination	[1]
433	GAIIVLTKSGRSAHQ	acetylation	[2, 12]
433	GAIIVLTKSGRSAHQ	ubiquitination	[1, 5, 13, 14, 15]
475	GIFPVLCKDPVQEAW	acetylation	[16]
475	GIFPVLCKDPVQEAW	ubiquitination	[1, 5, 13, 14, 15, 17]
498	NFAMNVGKARGFFKK	ubiquitination	[1, 4, 5, 6, 7, 13, 15, 18]
505	KARGFFKKGDVVIVL	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [3] Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth.
 Lv L, Li D, Zhao D, Lin R, Chu Y, Zhang H, Zha Z, Liu Y, Li Z, Xu Y, Wang G, Huang Y, Xiong Y, Guan KL, Lei QY.
 Mol Cell. 2011 Jun 24;42(6):719-30. [PMID: 21700219]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [6] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [7] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [8] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [9] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [10] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [11] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [12] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [13] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [14] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [15] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [16] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [17] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [18] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661] 

Functional Description

 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. 

Sequence Annotation

 REGION 307 531 Interaction with POU5F1.
 REGION 389 433 Intersubunit contact.
 REGION 432 437 D-fructose 1,6-bisphosphate binding; part
 REGION 514 521 D-fructose 1,6-bisphosphate binding; part
 METAL 75 75 Potassium (By similarity).
 METAL 77 77 Potassium (By similarity).
 METAL 113 113 Potassium.
 METAL 114 114 Potassium; via carbonyl oxygen (By
 METAL 272 272 Magnesium.
 METAL 296 296 Magnesium.
 BINDING 70 70 Serine.
 BINDING 73 73 Substrate (By similarity).
 BINDING 106 106 Serine.
 BINDING 295 295 Substrate; via amide nitrogen (By
 BINDING 296 296 Substrate; via amide nitrogen (By
 BINDING 328 328 Substrate (By similarity).
 BINDING 464 464 Serine.
 BINDING 482 482 D-fructose 1,6-bisphosphate; part of
 BINDING 489 489 D-fructose 1,6-bisphosphate; part of
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 37 37 Phosphoserine.
 MOD_RES 62 62 N6-acetyllysine.
 MOD_RES 89 89 N6-acetyllysine.
 MOD_RES 105 105 Phosphotyrosine.
 MOD_RES 148 148 Phosphotyrosine (By similarity).
 MOD_RES 166 166 N6-acetyllysine.
 MOD_RES 175 175 Phosphotyrosine.
 MOD_RES 195 195 Phosphothreonine.
 MOD_RES 266 266 N6-acetyllysine.
 MOD_RES 305 305 N6-acetyllysine.
 MOD_RES 403 403 4-hydroxyproline.
 MOD_RES 408 408 4-hydroxyproline.
 MOD_RES 433 433 N6-acetyllysine.  

Keyword

 3D-structure; Acetylation; Allosteric enzyme; Alternative splicing; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; Glycolysis; Hydroxylation; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Potassium; Pyruvate; Reference proteome; Transferase; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 531 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; NAS:UniProtKB.
 GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
 GO:0005739; C:mitochondrion; IEA:Compara.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0005886; C:plasma membrane; IDA:HPA.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0000287; F:magnesium ion binding; IEA:InterPro.
 GO:0030955; F:potassium ion binding; IEA:InterPro.
 GO:0004743; F:pyruvate kinase activity; TAS:UniProtKB.
 GO:0006096; P:glycolysis; NAS:UniProtKB.
 GO:0012501; P:programmed cell death; IDA:UniProtKB.
 GO:0044281; P:small molecule metabolic process; TAS:Reactome. 

Interpro

 IPR001697; 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. 

Pfam

 PF00224; PK
 PF02887; PK_C 

SMART

  

PROSITE

 PS00110; PYRUVATE_KINASE 

PRINTS

 PR01050; PYRUVTKNASE.