ID KPYM_HUMAN Reviewed; 531 AA. AC P14618; A6NFK3; B2R5N8; B3KRY0; B4DFX8; B4DUU6; P14786; Q53GK4; Q96E76; AC Q9BWB5; Q9UCV6; Q9UPF2; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 4. DT 02-SEP-2026, entry version 283. DE RecName: Full=Pyruvate kinase PKM; DE EC=2.7.1.40 {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:20847263}; DE AltName: Full=Cytosolic thyroid hormone-binding protein {ECO:0000303|PubMed:2813362}; DE Short=CTHBP {ECO:0000303|PubMed:2813362}; DE AltName: Full=Opa-interacting protein 3 {ECO:0000303|PubMed:9466265}; DE Short=OIP-3 {ECO:0000303|PubMed:9466265}; DE AltName: Full=Pyruvate kinase 2/3; DE AltName: Full=Pyruvate kinase muscle isozyme; DE AltName: Full=Threonine-protein kinase PKM2 {ECO:0000305}; DE EC=2.7.11.1 {ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661}; DE AltName: Full=Thyroid hormone-binding protein 1; DE Short=THBP1; DE AltName: Full=Tumor M2-PK; DE AltName: Full=Tyrosine-protein kinase PKM2 {ECO:0000305}; DE EC=2.7.10.2 {ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:24120661}; DE AltName: Full=p58; GN Name=PKM; Synonyms=OIP3 {ECO:0000303|PubMed:9466265}, PK2, PK3, PKM2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M2). RC TISSUE=Liver; RX PubMed=2854097; DOI=10.1016/0378-1119(88)90515-x; RA Tani K., Yoshida M.C., Satoh H., Mitamura K., Noguchi T., Tanaka T., RA Fujii H., Miwa S.; RT "Human M2-type pyruvate kinase: cDNA cloning, chromosomal assignment and RT expression in hepatoma."; RL Gene 73:509-516(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M2), PROTEIN SEQUENCE OF 70-98, RP SUBUNIT, AND ACTIVITY REGULATION. RX PubMed=2813362; DOI=10.1073/pnas.86.20.7861; RA Kato H., Fukuda T., Parkison C., McPhie P., Cheng S.-Y.; RT "Cytosolic thyroid hormone-binding protein is a monomer of pyruvate RT kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 86:7861-7865(1989). RN [3] RP ERRATUM OF PUBMED:2813362. RA Kato H., Fukuda T., Parkison C., McPhie P., Cheng S.-Y.; RL Proc. Natl. Acad. Sci. U.S.A. 87:1625-1625(1990). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING. RX PubMed=2040271; DOI=10.1111/j.1432-1033.1991.tb15991.x; RA Takenaka M., Noguchi T., Sadahiro S., Hirai H., Yamada K., Matsuda T., RA Imai E., Tanaka T.; RT "Isolation and characterization of the human pyruvate kinase M gene."; RL Eur. J. Biochem. 198:101-106(1991). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS M1 AND 3). RC TISSUE=Astrocyte, and Fetal brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM M2). RC TISSUE=Kidney; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM M2), AND VARIANT VAL-204. RC TISSUE=Kidney, Lung carcinoma, Ovary, Retina, and Rhabdomyosarcoma; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP PROTEIN SEQUENCE OF 2-43; 57-73; 93-115; 126-135; 167-186; 231-246; RP 271-311; 401-422; 448-455 AND 490-498, CLEAVAGE OF INITIATOR METHIONINE, RP ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=B-cell lymphoma; RA Bienvenut W.V.; RL Submitted (JUL-2005) to UniProtKB. RN [12] RP PROTEIN SEQUENCE OF 2-18, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND INTERACTION WITH RP THYROID HORMONE. RX PubMed=1854723; DOI=10.1021/bi00243a010; RA Ashizawa K., McPhie P., Lin K.-H., Cheng S.-Y.; RT "An in vitro novel mechanism of regulating the activity of pyruvate kinase RT M2 by thyroid hormone and fructose 1, 6-bisphosphate."; RL Biochemistry 30:7105-7111(1991). RN [13] RP PROTEIN SEQUENCE OF 2-32. RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [14] RP PROTEIN SEQUENCE OF 74-89, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Brain, and Cajal-Retzius cell; RA Lubec G., Vishwanath V.; RL Submitted (MAR-2007) to UniProtKB. RN [15] RP PROTEIN SEQUENCE OF 174-186; 295-305 AND 401-422 (ISOFORMS M2/3), RP INTERACTION WITH TRIM35 (ISOFORM M2), SUBCELLULAR LOCATION, AND MASS RP SPECTROMETRY. RX PubMed=25263439; DOI=10.1038/onc.2014.325; RA Chen Z., Wang Z., Guo W., Zhang Z., Zhao F., Zhao Y., Jia D., Ding J., RA Wang H., Yao M., He X.; RT "TRIM35 Interacts with pyruvate kinase isoform M2 to suppress the Warburg RT effect and tumorigenicity in hepatocellular carcinoma."; RL Oncogene 34:3946-3956(2015). RN [16] RP NUCLEOTIDE SEQUENCE [MRNA] OF 368-531 (ISOFORM M2). RX PubMed=9466265; DOI=10.1046/j.1365-2958.1998.00670.x; RA Williams J.M., Chen G.-C., Zhu L., Rest R.F.; RT "Using the yeast two-hybrid system to identify human epithelial cell RT proteins that bind gonococcal Opa proteins: intracellular gonococci bind RT pyruvate kinase via their Opa proteins and require host pyruvate for RT growth."; RL Mol. Microbiol. 27:171-186(1998). RN [17] RP INTERACTION WITH HERC1. RX PubMed=12650930; DOI=10.1016/s0014-5793(03)00205-9; RA Garcia-Gonzalo F.R., Cruz C., Munoz P., Mazurek S., Eigenbrodt E., RA Ventura F., Bartrons R., Rosa J.L.; RT "Interaction between HERC1 and M2-type pyruvate kinase."; RL FEBS Lett. 539:78-84(2003). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Lymphoblast; RX PubMed=14654843; DOI=10.1038/nature02166; RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.; RT "Proteomic characterization of the human centrosome by protein correlation RT profiling."; RL Nature 426:570-574(2003). RN [19] RP ISGYLATION. RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132; RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J., RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.; RT "Proteomic identification of proteins conjugated to ISG15 in mouse and RT human cells."; RL Biochem. Biophys. Res. Commun. 336:496-506(2005). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [23] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=17308100; DOI=10.1158/0008-5472.can-06-2870; RA Stetak A., Veress R., Ovadi J., Csermely P., Keri G., Ullrich A.; RT "Nuclear translocation of the tumor marker pyruvate kinase M2 induces RT programmed cell death."; RL Cancer Res. 67:1602-1608(2007). RN [24] RP INTERACTION WITH PML, ACTIVITY REGULATION, SUBUNIT, AND SUBCELLULAR RP LOCATION. RX PubMed=18298799; DOI=10.1111/j.1365-2443.2008.01165.x; RA Shimada N., Shinagawa T., Ishii S.; RT "Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML RT tumor suppressor protein."; RL Genes Cells 13:245-254(2008). RN [25] RP INTERACTION WITH POU5F1, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=18191611; DOI=10.1016/j.biocel.2007.11.009; RA Lee J., Kim H.K., Han Y.-M., Kim J.; RT "Pyruvate kinase isozyme type M2 (PKM2) interacts and cooperates with Oct-4 RT in regulating transcription."; RL Int. J. Biochem. Cell Biol. 40:1043-1054(2008). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [28] RP FUNCTION (ISOFORMS M1 AND M2), TISSUE SPECIFICITY (ISOFORMS M1 AND M2), AND RP DEVELOPMENTAL STAGE (ISOFORMS M1 AND M2). RX PubMed=18337823; DOI=10.1038/nature06734; RA Christofk H.R., Vander Heiden M.G., Harris M.H., Ramanathan A., RA Gerszten R.E., Wei R., Fleming M.D., Schreiber S.L., Cantley L.C.; RT "The M2 splice isoform of pyruvate kinase is important for cancer RT metabolism and tumour growth."; RL Nature 452:230-233(2008). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [30] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37; TYR-175 AND THR-195, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [32] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-62; LYS-89; LYS-166; LYS-266 AND RP LYS-433, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [33] RP FUNCTION (ISOFORMS M1 AND M2), AND CATALYTIC ACTIVITY (ISOFORMS M1 AND M2). RX PubMed=20847263; DOI=10.1126/science.1188015; RA Vander Heiden M.G., Locasale J.W., Swanson K.D., Sharfi H., Heffron G.J., RA Amador-Noguez D., Christofk H.R., Wagner G., Rabinowitz J.D., Asara J.M., RA Cantley L.C.; RT "Evidence for an alternative glycolytic pathway in rapidly proliferating RT cells."; RL Science 329:1492-1499(2010). RN [34] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [35] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [36] RP INTERACTION WITH EGLN3 AND HIF1A, SUBCELLULAR LOCATION, INDUCTION, RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, HYDROXYLATION AT PRO-403 AND RP PRO-408, AND MUTAGENESIS OF PRO-403 AND PRO-408. RX PubMed=21620138; DOI=10.1016/j.cell.2011.03.054; RA Luo W., Hu H., Chang R., Zhong J., Knabel M., O'Meally R., Cole R.N., RA Pandey A., Semenza G.L.; RT "Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible RT factor 1."; RL Cell 145:732-744(2011). RN [37] RP INTERACTION WITH EGLN3. RX PubMed=21483450; DOI=10.1038/cr.2011.66; RA Chen N., Rinner O., Czernik D., Nytko K.J., Zheng D., Stiehl D.P., RA Zamboni N., Gstaiger M., Frei C.; RT "The oxygen sensor PHD3 limits glycolysis under hypoxia via direct binding RT to pyruvate kinase."; RL Cell Res. 21:983-986(2011). RN [38] RP ACETYLATION AT LYS-305. RX PubMed=21700219; DOI=10.1016/j.molcel.2011.04.025; RA Lv L., Li D., Zhao D., Lin R., Chu Y., Zhang H., Zha Z., Liu Y., Li Z., RA Xu Y., Wang G., Huang Y., Xiong Y., Guan K.L., Lei Q.Y.; RT "Acetylation targets the M2 isoform of pyruvate kinase for degradation RT through chaperone-mediated autophagy and promotes tumor growth."; RL Mol. Cell 42:719-730(2011). RN [39] RP FUNCTION (ISOFORM M2), SUBCELLULAR LOCATION (ISOFORM M2), INTERACTION WITH RP CTNNB1 (ISOFORM M2), AND MUTAGENESIS OF LYS-367 AND LYS-433. RX PubMed=22056988; DOI=10.1038/nature10598; RA Yang W., Xia Y., Ji H., Zheng Y., Liang J., Huang W., Gao X., Aldape K., RA Lu Z.; RT "Nuclear PKM2 regulates beta-catenin transactivation upon EGFR RT activation."; RL Nature 480:118-122(2011). RN [40] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [41] RP FUNCTION (ISOFORM M2), CATALYTIC ACTIVITY (ISOFORM M2), SUBCELLULAR RP LOCATION (ISOFORM M2), AND MUTAGENESIS OF LYS-367 AND LYS-433. RX PubMed=22901803; DOI=10.1016/j.cell.2012.07.018; RA Yang W., Xia Y., Hawke D., Li X., Liang J., Xing D., Aldape K., Hunter T., RA Alfred Yung W.K., Lu Z.; RT "PKM2 phosphorylates histone H3 and promotes gene transcription and RT tumorigenesis."; RL Cell 150:685-696(2012). RN [42] RP FUNCTION (ISOFORM M2), CATALYTIC ACTIVITY (ISOFORM M2), SUBCELLULAR RP LOCATION (ISOFORM M2), SUBUNIT (ISOFORM M2), AND MUTAGENESIS OF ARG-399. RX PubMed=22306293; DOI=10.1016/j.molcel.2012.01.001; RA Gao X., Wang H., Yang J.J., Liu X., Liu Z.R.; RT "Pyruvate kinase M2 regulates gene transcription by acting as a protein RT kinase."; RL Mol. Cell 45:598-609(2012). RN [43] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37; THR-41; TYR-105 AND RP SER-127, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [44] RP FUNCTION (ISOFORM M2), CATALYTIC ACTIVITY (ISOFORM M2), ACTIVITY REGULATION RP (ISOFORM M2), SUBCELLULAR LOCATION (ISOFORM M2), SUBUNIT (ISOFORM M2), RP ACETYLATION AT LYS-433 (ISOFORM M2), AND MUTAGENESIS OF LYS-433. RX PubMed=24120661; DOI=10.1016/j.molcel.2013.09.004; RA Lv L., Xu Y.P., Zhao D., Li F.L., Wang W., Sasaki N., Jiang Y., Zhou X., RA Li T.T., Guan K.L., Lei Q.Y., Xiong Y.; RT "Mitogenic and oncogenic stimulation of K433 acetylation promotes PKM2 RT protein kinase activity and nuclear localization."; RL Mol. Cell 52:340-352(2013). RN [45] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [46] RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-3, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Colon carcinoma; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [47] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-166, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25114211; DOI=10.1073/pnas.1413825111; RA Impens F., Radoshevich L., Cossart P., Ribet D.; RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by RT external stimuli."; RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014). RN [48] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [49] RP INTERACTION WITH JMJD8. RX PubMed=27199445; DOI=10.1161/atvbaha.116.307695; RA Boeckel J.N., Derlet A., Glaser S.F., Luczak A., Lucas T., Heumueller A.W., RA Krueger M., Zehendner C.M., Kaluza D., Doddaballapur A., Ohtani K., RA Treguer K., Dimmeler S.; RT "JMJD8 Regulates Angiogenic Sprouting and Cellular Metabolism by RT Interacting With Pyruvate Kinase M2 in Endothelial Cells."; RL Arterioscler. Thromb. Vasc. Biol. 36:1425-1433(2016). RN [50] RP INTERACTION WITH TSC22D2, AND SUBCELLULAR LOCATION. RX PubMed=27573352; DOI=10.3892/ijo.2016.3599; RA Liang F., Li Q., Li X., Li Z., Gong Z., Deng H., Xiang B., Zhou M., Li X., RA Li G., Zeng Z., Xiong W.; RT "TSC22D2 interacts with PKM2 and inhibits cell growth in colorectal RT cancer."; RL Int. J. Oncol. 49:1046-1056(2016). RN [51] RP FUNCTION (ISOFORM M2), SUBCELLULAR LOCATION (ISOFORM M2), ACETYLATION AT RP LYS-433 (ISOFORM M2), DEACETYLATION BY SIRT6 (ISOFORM M2), AND MUTAGENESIS RP OF LYS-433. RX PubMed=26787900; DOI=10.1073/pnas.1520045113; RA Bhardwaj A., Das S.; RT "SIRT6 deacetylates PKM2 to suppress its nuclear localization and oncogenic RT functions."; RL Proc. Natl. Acad. Sci. U.S.A. 113:E538-E547(2016). RN [52] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-115; LYS-266 AND LYS-270, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [53] RP S-NITROSYLATION AT CYS-423 AND CYS-424 (ISOFORM M2), AND MUTAGENESIS OF RP 423-CYS-CYS-424. RX PubMed=30487609; DOI=10.1038/s41586-018-0749-z; RA Zhou H.L., Zhang R., Anand P., Stomberski C.T., Qian Z., Hausladen A., RA Wang L., Rhee E.P., Parikh S.M., Karumanchi S.A., Stamler J.S.; RT "Metabolic reprogramming by the S-nitroso-CoA reductase system protects RT against kidney injury."; RL Nature 565:96-100(2019). RN [54] RP INTERACTION WITH TRAF4, AND SUBCELLULAR LOCATION. RX PubMed=32268273; DOI=10.1016/j.ebiom.2020.102722; RA Cen S., Li J., Cai Z., Pan Y., Sun Z., Li Z., Ye G., Zheng G., Li M., RA Liu W., Yu W., Wang S., Xie Z., Wang P., Shen H.; RT "TRAF4 acts as a fate checkpoint to regulate the adipogenic differentiation RT of MSCs by activating PKM2."; RL EBioMedicine 54:102722-102722(2020). RN [55] RP FUNCTION (ISOFORM M2), AND INTERACTION WITH FOXM1 (ISOFORM M2). RX PubMed=33314660; DOI=10.1002/1878-0261.12879; RA Zhang W., Zhang X., Huang S., Chen J., Ding P., Wang Q., Li L., Lv X., RA Li L., Zhang P., Zhou D., Wen W., Wang Y., Lei Q.Y., Wu J., Hu W.; RT "FOXM1D potentiates PKM2-mediated tumor glycolysis and angiogenesis."; RL Mol. Oncol. 15:1466-1485(2021). RN [56] RP X-RAY CRYSTALLOGRAPHY (2.82 ANGSTROMS) OF ISOFORM M2 IN COMPLEX WITH RP OXALATE AND FBP, CATALYTIC ACTIVITY, SUBUNIT, ENZYME MECHANISM, ACTIVITY RP REGULATION, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=15996096; DOI=10.1021/bi0474923; RA Dombrauckas J.D., Santarsiero B.D., Mesecar A.D.; RT "Structural basis for tumor pyruvate kinase M2 allosteric regulation and RT catalysis."; RL Biochemistry 44:9417-9429(2005). RN [57] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS). RG Structural genomics consortium (SGC); RT "Structure of human muscle pyruvate kinase (PKM2)."; RL Submitted (MAY-2005) to the PDB data bank. RN [58] RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 14-531 ALONE AND IN COMPLEX WITH RP FBP, FUNCTION, AND ACTIVITY REGULATION. RX PubMed=18337815; DOI=10.1038/nature06667; RA Christofk H.R., Vander Heiden M.G., Wu N., Asara J.M., Cantley L.C.; RT "Pyruvate kinase M2 is a phosphotyrosine-binding protein."; RL Nature 452:181-186(2008). RN [59] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 2-531, ACTIVITY REGULATION BY RP SERINE, MAGNESIUM-BINDING SITES, SUBUNIT, AND MUTAGENESIS OF SER-437 AND RP HIS-464. RX PubMed=23064226; DOI=10.1038/nature11540; RA Chaneton B., Hillmann P., Zheng L., Martin A.C., Maddocks O.D., RA Chokkathukalam A., Coyle J.E., Jankevics A., Holding F.P., Vousden K.H., RA Frezza C., O'Reilly M., Gottlieb E.; RT "Serine is a natural ligand and allosteric activator of pyruvate kinase RT M2."; RL Nature 491:458-462(2012). RN [60] RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) IN COMPLEX WITH ATP; RP FRUCTOSE-1-6-DIPHOSPHATE; MAGNESIUM IONS AND POTASSIUM IONS. RX PubMed=23530218; DOI=10.1073/pnas.1217157110; RA Morgan H.P., O'Reilly F.J., Wear M.A., O'Neill J.R., RA Fothergill-Gilmore L.A., Hupp T., Walkinshaw M.D.; RT "M2 pyruvate kinase provides a mechanism for nutrient sensing and RT regulation of cell proliferation."; RL Proc. Natl. Acad. Sci. U.S.A. 110:5881-5886(2013). CC -!- FUNCTION: Catalyzes the final rate-limiting step of glycolysis by CC mediating the transfer of a phosphoryl group from phosphoenolpyruvate CC (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, CC PubMed:20847263). The ratio between the highly active tetrameric form CC and nearly inactive dimeric form determines whether glucose carbons are CC channeled to biosynthetic processes or used for glycolytic ATP CC production (PubMed:15996096, PubMed:1854723, PubMed:20847263). The CC transition between the 2 forms contributes to the control of glycolysis CC and is important for tumor cell proliferation and survival CC (PubMed:15996096, PubMed:1854723, PubMed:20847263). CC {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723, CC ECO:0000269|PubMed:20847263}. CC -!- FUNCTION: [Isoform M2]: Isoform specifically expressed during CC embryogenesis that has low pyruvate kinase activity by itself and CC requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for CC pyruvate kinase activity (PubMed:18337823, PubMed:20847263). In CC addition to its pyruvate kinase activity in the cytoplasm, also acts as CC a regulator of transcription in the nucleus by acting as a protein CC kinase (PubMed:18191611, PubMed:21620138, PubMed:22056988, CC PubMed:22306293, PubMed:22901803, PubMed:24120661). Translocates into CC the nucleus in response to various signals, such as EGF receptor CC activation, and homodimerizes, leading to its conversion into a protein CC threonine- and tyrosine-protein kinase (PubMed:22056988, CC PubMed:22306293, PubMed:22901803, PubMed:24120661, PubMed:26787900). CC Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr- CC 11' (H3T11ph), leading to activate transcription (PubMed:22306293, CC PubMed:22901803, PubMed:24120661). Promotes transcription of VEGFA CC following translocation to the nucleus along with the NFKB1/p50 and CC RELA/p65 subunits of the NF-kappa-B transcription factor complex which CC is triggered by interaction with FOXM1 isoform 5 (FOXM1D) and leads to CC increased angiogenesis (PubMed:33314660). Its ability to activate CC transcription plays a role in cancer cells by promoting cell CC proliferation and promote tumorigenesis (PubMed:18337823, CC PubMed:22901803, PubMed:26787900). Promotes the expression of the CC immune checkpoint protein CD274 in BMAL1-deficient macrophages (By CC similarity). May also act as a translation regulator for a subset of CC mRNAs, independently of its pyruvate kinase activity: associates with CC subpools of endoplasmic reticulum-associated ribosomes, binds directly CC to the mRNAs translated at the endoplasmic reticulum and promotes CC translation of these endoplasmic reticulum-destined mRNAs (By CC similarity). Plays a role in caspase independent cell death of tumor CC cells (PubMed:17308100). {ECO:0000250|UniProtKB:P52480, CC ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, CC ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263, CC ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22056988, CC ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:22901803, CC ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900, CC ECO:0000269|PubMed:33314660}. CC -!- FUNCTION: [Isoform M1]: Pyruvate kinase isoform expressed in adult CC tissues, which replaces isoform M2 after birth (PubMed:18337823). In CC contrast to isoform M2, has high pyruvate kinase activity by itself and CC does not require allosteric activation by D-fructose 1,6-bisphosphate CC (FBP) for activity (PubMed:20847263). {ECO:0000269|PubMed:18337823, CC ECO:0000269|PubMed:20847263}. CC -!- CATALYTIC ACTIVITY: [Isoform M2]: CC Reaction=pyruvate + ATP = phosphoenolpyruvate + ADP + H(+); CC Xref=Rhea:RHEA:18157, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58702, ChEBI:CHEBI:456216; CC EC=2.7.1.40; Evidence={ECO:0000269|PubMed:15996096, CC ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:20847263}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18159; CC Evidence={ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723, CC ECO:0000269|PubMed:20847263}; CC -!- CATALYTIC ACTIVITY: [Isoform M2]: CC Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:61978, ChEBI:CHEBI:456216; EC=2.7.10.2; CC Evidence={ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:24120661}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10597; CC Evidence={ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:24120661}; CC -!- CATALYTIC ACTIVITY: [Isoform M2]: CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609; CC Evidence={ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661}; CC -!- CATALYTIC ACTIVITY: [Isoform M1]: CC Reaction=pyruvate + ATP = phosphoenolpyruvate + ADP + H(+); CC Xref=Rhea:RHEA:18157, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58702, ChEBI:CHEBI:456216; CC EC=2.7.1.40; Evidence={ECO:0000269|PubMed:20847263}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000305|PubMed:23530218}; CC -!- COFACTOR: CC Name=K(+); Xref=ChEBI:CHEBI:29103; CC Evidence={ECO:0000305|PubMed:23530218}; CC -!- ACTIVITY REGULATION: [Isoform M2]: Isoform M2 is allosterically CC activated by D-fructose 1,6-bisphosphate (FBP) (PubMed:15996096, CC PubMed:18337815, PubMed:1854723, PubMed:2813362). Inhibited by oxalate CC and 3,3',5-triiodo-L-thyronine (T3) (PubMed:15996096). The activity of CC the tetrameric form is inhibited by PML (PubMed:18298799). Selective CC binding to tyrosine-phosphorylated peptides releases the allosteric CC activator FBP, leading to inhibition of PKM enzymatic activity, this CC diverts glucose metabolites from energy production to anabolic CC processes when cells are stimulated by certain growth factors CC (PubMed:18337815). Glycolytic flux are highly dependent on de novo CC biosynthesis of serine and glycine, and serine is a natural ligand and CC allosteric activator of isoform M2 (PubMed:23064226). Acetylation at CC Lys-433 promotes its translocation into the nucleus and CC homodimerization, promoting the protein kinase activity CC (PubMed:24120661). {ECO:0000269|PubMed:15996096, CC ECO:0000269|PubMed:18298799, ECO:0000269|PubMed:18337815, CC ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:23064226, CC ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:2813362}. CC -!- ACTIVITY REGULATION: [Isoform M1]: Has high pyruvate kinase activity by CC itself and does not require allosteric activation by D-fructose 1,6- CC bisphosphate (FBP) for activity. {ECO:0000269|PubMed:20847263}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=2.7 mM for phosphoenolpyruvate (at 32 degrees Celsius, pH 8.0) CC {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723}; CC KM=0.17 mM for phosphoenolpyruvate (in the presence of 2 mM CC D-fructose 1,6-bisphosphate (FBP), at 32 degrees Celsius, pH 8.0) CC {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723}; CC KM=0.34 mM for ADP (at 32 degrees Celsius, pH 8.0) CC {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723}; CC KM=0.24 mM for ADP (in the presence of 2 mM FBP, at 32 degrees CC Celsius, pH 8.0) {ECO:0000269|PubMed:15996096, CC ECO:0000269|PubMed:1854723}; CC KM=0.13 mM for phosphoenolpyruvate (in the presence of 2 mM FBP, at CC 25 degrees Celsius) {ECO:0000269|PubMed:15996096, CC ECO:0000269|PubMed:1854723}; CC KM=0.63 mM for ADP (in the presence of 2 mM FBP, at 25 degrees CC Celsius) {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723}; CC pH dependence: CC Optimum pH for T3 binding is 6.0-6.5. Increase in pH causes T3 CC binding to drop, does not bind T3 above pH 9.0 or below pH 5.0. CC {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723}; CC -!- PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D- CC glyceraldehyde 3-phosphate: step 5/5. {ECO:0000269|PubMed:15996096, CC ECO:0000269|PubMed:1854723}. CC -!- SUBUNIT: [Isoform M2]: Monomer and homotetramer; exists as a monomer in CC the absence of D-fructose 1,6-bisphosphate (FBP), and reversibly CC associates to form a homotetramer in the presence of FBP CC (PubMed:15996096, PubMed:18298799, PubMed:18337815, PubMed:1854723, CC PubMed:23064226, PubMed:2813362). The monomeric form binds 3,3',5- CC triiodo-L-thyronine (T3) (PubMed:15996096). Tetramer formation induces CC pyruvate kinase activity (PubMed:15996096, PubMed:18298799, CC PubMed:18337815, PubMed:1854723, PubMed:23064226, PubMed:2813362). The CC tetrameric form has high affinity for the substrate and is associated CC within the glycolytic enzyme complex (PubMed:15996096, PubMed:18298799, CC PubMed:18337815, PubMed:1854723, PubMed:23064226, PubMed:2813362). FBP CC stimulates the formation of tetramers from dimers (PubMed:15996096, CC PubMed:18298799, PubMed:18337815, PubMed:1854723, PubMed:23064226, CC PubMed:2813362). Homodimer; exists in a dimeric form in tumor cells and CC the dimeric form has less affinity for the phosphoenolpyruvate CC substrate (PubMed:22306293, PubMed:24120661). The homodimer converts CC into a protein kinase (PubMed:22306293, PubMed:24120661). Interacts CC with HERC1, POU5F1 and PML (PubMed:12650930, PubMed:18191611). CC Interacts with EGLN3; the interaction hydroxylates PKM under hypoxia CC and enhances binding to HIF1A (PubMed:21483450, PubMed:21620138). CC Interacts with HIF1A; the interaction is enhanced by binding of EGLN3, CC promoting enhanced transcription activity under hypoxia CC (PubMed:21620138). Interacts with TRIM35; this interaction prevents CC FGFR1-dependent tyrosine phosphorylation (PubMed:25263439). Interacts CC with JMJD8 (PubMed:27199445). Interacts with TRAF4 (PubMed:32268273). CC Interacts with (phosphorylated) CTNNB1; leading to activate CC transcription (PubMed:22056988). Interacts with TSC22D2; the CC interaction results in reduced nuclear levels of PKM isoform M2, CC leading to repression of cyclin CCND1 transcription and reduced cell CC growth (PubMed:27573352). Interacts with FOXM1 isoform 5 (FOXM1D); CC FOXM1D binds to the PKM2 homotetramer to form a heterooctamer, CC consisting of the PKM2 homotetramer with 4 copies of FOXM1, which CC reduces PKM2 activity, leading to promotion of glycolysis CC (PubMed:33314660). Interaction with FOXM1D also promotes nuclear CC translocation of PKM2 along with the NFKB1/p50 and RELA/p65 subunits of CC the NF-kappa-B transcription factor complex, leading to increased VEGFA CC transcription and angiogenesis (PubMed:33314660). CC {ECO:0000269|PubMed:12650930, ECO:0000269|PubMed:15996096, CC ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:18298799, CC ECO:0000269|PubMed:18337815, ECO:0000269|PubMed:1854723, CC ECO:0000269|PubMed:21483450, ECO:0000269|PubMed:21620138, CC ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22306293, CC ECO:0000269|PubMed:23064226, ECO:0000269|PubMed:24120661, CC ECO:0000269|PubMed:25263439, ECO:0000269|PubMed:27199445, CC ECO:0000269|PubMed:27573352, ECO:0000269|PubMed:2813362, CC ECO:0000269|PubMed:32268273, ECO:0000269|PubMed:33314660}. CC -!- SUBUNIT: (Microbial infection) Binding to certain oncoproteins such as CC HPV-16 E7 oncoprotein promotes homodimerization. CC {ECO:0000269|PubMed:24120661}. CC -!- INTERACTION: CC P14618; P49407: ARRB1; NbExp=3; IntAct=EBI-353408, EBI-743313; CC P14618; P32121: ARRB2; NbExp=4; IntAct=EBI-353408, EBI-714559; CC P14618; Q96IK1-2: BOD1; NbExp=3; IntAct=EBI-353408, EBI-18924329; CC P14618; P35222: CTNNB1; NbExp=4; IntAct=EBI-353408, EBI-491549; CC P14618; P53355: DAPK1; NbExp=3; IntAct=EBI-353408, EBI-358616; CC P14618; P22607: FGFR3; NbExp=3; IntAct=EBI-353408, EBI-348399; CC P14618; P42858: HTT; NbExp=9; IntAct=EBI-353408, EBI-466029; CC P14618; P04049: RAF1; NbExp=3; IntAct=EBI-353408, EBI-365996; CC P14618; Q8N488: RYBP; NbExp=3; IntAct=EBI-353408, EBI-752324; CC P14618; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-353408, EBI-5235340; CC P14618; Q9BSI4: TINF2; NbExp=2; IntAct=EBI-353408, EBI-717399; CC P14618; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-353408, EBI-741480; CC P14618; Q9Y649; NbExp=3; IntAct=EBI-353408, EBI-25900580; CC P14618; Q9WMX2; Xeno; NbExp=4; IntAct=EBI-353408, EBI-710918; CC P14618-1; P35222: CTNNB1; NbExp=3; IntAct=EBI-4304679, EBI-491549; CC P14618-1; P53355: DAPK1; NbExp=2; IntAct=EBI-4304679, EBI-358616; CC P14618-1; Q9H6Z9: EGLN3; NbExp=2; IntAct=EBI-4304679, EBI-1175354; CC P14618-1; P68431: H3C12; NbExp=3; IntAct=EBI-4304679, EBI-79722; CC P14618-1; Q16665: HIF1A; NbExp=7; IntAct=EBI-4304679, EBI-447269; CC P14618-1; P27361: MAPK3; NbExp=3; IntAct=EBI-4304679, EBI-73995; CC -!- SUBCELLULAR LOCATION: [Isoform M2]: Cytoplasm CC {ECO:0000269|PubMed:25263439, ECO:0000269|PubMed:26787900, CC ECO:0000269|PubMed:27573352, ECO:0000269|PubMed:32268273}. Nucleus CC {ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, CC ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22901803, CC ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900, CC ECO:0000269|PubMed:27573352, ECO:0000269|PubMed:32268273}. CC Note=Translocates to the nucleus in response to various signals, such CC as EGF receptor activation or apoptotic stimuli (PubMed:17308100, CC PubMed:22056988, PubMed:24120661). Nuclear translocation is promoted by CC acetylation by EP300 (PubMed:24120661). Deacetylation by SIRT6 promotes CC its nuclear export in a process dependent of XPO4, thereby suppressing CC its ability to activate transcription and promote tumorigenesis CC (PubMed:26787900). {ECO:0000269|PubMed:17308100, CC ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:24120661, CC ECO:0000269|PubMed:26787900}. CC -!- SUBCELLULAR LOCATION: [Isoform M1]: Cytoplasm {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=M2 {ECO:0000303|PubMed:2854097}; Synonyms=M2-PK, PKM2; CC IsoId=P14618-1; Sequence=Displayed; CC Name=M1 {ECO:0000303|PubMed:2854097}; Synonyms=M1-PK, PKM1; CC IsoId=P14618-2, P14786-1; Sequence=VSP_011101; CC Name=3; CC IsoId=P14618-3; Sequence=VSP_043370; CC -!- TISSUE SPECIFICITY: [Isoform M2]: Specifically expressed in CC proliferating cells, such as embryonic stem cells, embryonic carcinoma CC cells, as well as cancer cells. {ECO:0000269|PubMed:18191611, CC ECO:0000269|PubMed:18337823}. CC -!- TISSUE SPECIFICITY: [Isoform M1]: Expressed in adult tissues CC (PubMed:18337823). Not expressed in tumor cells (PubMed:18337823). CC {ECO:0000269|PubMed:18337823}. CC -!- DEVELOPMENTAL STAGE: [Isoform M2]: Specifically expressed during CC embryonic development. {ECO:0000269|PubMed:18337823}. CC -!- DEVELOPMENTAL STAGE: [Isoform M1]: Specifically expressed in adult CC tissues. {ECO:0000269|PubMed:18337823}. CC -!- PTM: ISGylated. {ECO:0000269|PubMed:16139798}. CC -!- PTM: Under hypoxia, hydroxylated by EGLN3. CC {ECO:0000269|PubMed:21620138}. CC -!- PTM: Acetylation at Lys-305 is stimulated by high glucose CC concentration, it decreases enzyme activity and promotes its lysosomal- CC dependent degradation via chaperone-mediated autophagy. CC {ECO:0000269|PubMed:21700219, ECO:0000269|Ref.11}. CC -!- PTM: [Isoform M2]: Acetylated at Lys-433 by EP300, leading to impair CC phosphoenolpyruvate substrate-binding and promote its homodimerization CC and subsequent translocation to the nucleus (PubMed:24120661). CC Deacetylation at Lys-433 by SIRT6 promotes its nuclear export into the CC cytoplasm, leading to suppress its nuclear localization and oncogenic CC function (PubMed:26787900). {ECO:0000269|PubMed:24120661, CC ECO:0000269|PubMed:26787900}. CC -!- PTM: [Isoform M2]: S-nitrosylation at Cys-423 and Cys-424 inhibits CC homotetramerization and pyruvate kinase activity (PubMed:30487609). S- CC nitrosylation is indirectly inhibited by AKR1A1 which degrades S- CC nitroso-CoA, a cofactor required to S-nitrosylate proteins CC (PubMed:30487609). {ECO:0000269|PubMed:30487609}. CC -!- PTM: FGFR1-dependent tyrosine phosphorylation is reduced by interaction CC with TRIM35. {ECO:0000269|PubMed:25263439}. CC -!- MISCELLANEOUS: There are 4 isozymes of pyruvate kinase in mammals (L, CC R, M1, M2) encoded by 2 different genes: PKLR and PKM. The L and R CC isozymes are generated from the PKLR by differential splicing of RNA; CC the M1 and M2 forms are produced from the PKM gene by differential CC splicing. L type is major isozyme in the liver, R is found in red CC cells, M1 is the main form in muscle, heart and brain, and M2 is found CC in early fetal tissues as well as in most cancer cells. CC -!- SIMILARITY: Belongs to the pyruvate kinase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAG57589.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Pyruvate kinase entry; CC URL="https://en.wikipedia.org/wiki/Pyruvate_kinase"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41728/PKM2"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M23725; AAA36449.1; -; mRNA. DR EMBL; M26252; AAA36672.1; -; mRNA. DR EMBL; X56494; CAA39849.1; -; Genomic_DNA. DR EMBL; AK092369; BAG52542.1; -; mRNA. DR EMBL; AK222927; BAD96647.1; -; mRNA. DR EMBL; AK294315; BAG57589.1; ALT_INIT; mRNA. DR EMBL; AK300800; BAG62458.1; -; mRNA. DR EMBL; AK312253; BAG35185.1; -; mRNA. DR EMBL; AY352517; AAQ15274.1; -; Genomic_DNA. DR EMBL; AC020779; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471082; EAW77884.1; -; Genomic_DNA. DR EMBL; CH471082; EAW77888.1; -; Genomic_DNA. DR EMBL; BC000481; AAH00481.3; -; mRNA. DR EMBL; BC007640; AAH07640.1; -; mRNA. DR EMBL; BC007952; AAH07952.3; -; mRNA. DR EMBL; BC012811; AAH12811.3; -; mRNA. DR EMBL; BC035198; AAH35198.1; -; mRNA. DR EMBL; AF025439; AAC39559.1; -; mRNA. DR CCDS; CCDS32284.1; -. [P14618-1] DR CCDS; CCDS32285.1; -. [P14618-2] DR PIR; S30038; S30038. DR PIR; S64635; S64635. DR RefSeq; NP_001193725.1; NM_001206796.3. DR RefSeq; NP_001193726.1; NM_001206797.3. DR RefSeq; NP_001193727.1; NM_001206798.3. [P14618-3] DR RefSeq; NP_001193728.1; NM_001206799.2. DR RefSeq; NP_001303247.1; NM_001316318.2. DR RefSeq; NP_002645.3; NM_002654.6. [P14618-1] DR RefSeq; NP_872270.1; NM_182470.4. [P14618-2] DR RefSeq; NP_872271.1; NM_182471.4. [P14618-2] DR RefSeq; XP_005254502.1; XM_005254445.6. [P14618-1] DR RefSeq; XP_047288622.1; XM_047432666.1. [P14618-1] DR PDB; 1T5A; X-ray; 2.80 A; A/B/C/D=1-531. DR PDB; 1ZJH; X-ray; 2.20 A; A=3-531. DR PDB; 3BJF; X-ray; 2.03 A; A/B/C/D=14-531. DR PDB; 3BJT; X-ray; 2.50 A; A/B/C/D=2-531. DR PDB; 3G2G; X-ray; 2.00 A; A/B/C/D=1-531. DR PDB; 3GQY; X-ray; 1.85 A; A/B/C/D=1-531. DR PDB; 3GR4; X-ray; 1.60 A; A/B/C/D=1-531. DR PDB; 3H6O; X-ray; 2.00 A; A/B/C/D=1-531. DR PDB; 3ME3; X-ray; 1.95 A; A/B/C/D=1-531. DR PDB; 3SRD; X-ray; 2.90 A; A/B/C/D=1-531. DR PDB; 3SRF; X-ray; 2.84 A; A/B/C/D/E/F/G/H=1-531. DR PDB; 3SRH; X-ray; 2.60 A; A/B/C/D=1-531. DR PDB; 3U2Z; X-ray; 2.10 A; A/B/C/D=1-531. DR PDB; 4B2D; X-ray; 2.30 A; A/B/C/D=2-531. DR PDB; 4FXF; X-ray; 2.55 A; A/B/C/D=1-531. DR PDB; 4FXJ; X-ray; 2.90 A; A/B/C/D=1-531. DR PDB; 4G1N; X-ray; 2.30 A; A/B/C/D=14-531. DR PDB; 4JPG; X-ray; 2.33 A; A/B/C/D=1-531. DR PDB; 4QG6; X-ray; 3.21 A; A/B/C/D=1-531. DR PDB; 4QG8; X-ray; 2.30 A; A/B/C/D=1-531. DR PDB; 4QG9; X-ray; 2.38 A; A/B/C/D=1-531. DR PDB; 4QGC; X-ray; 2.30 A; A/B/C/D=1-531. DR PDB; 4RPP; X-ray; 2.58 A; A/B/C/D=1-531. DR PDB; 4WJ8; X-ray; 2.87 A; A/B/C/D=1-531. DR PDB; 4YJ5; X-ray; 2.41 A; A/B/C/D=14-531. DR PDB; 5X0I; X-ray; 2.64 A; A/B/C/D=1-531. DR PDB; 5X1V; X-ray; 2.10 A; A/B/C/D=1-531. DR PDB; 5X1W; X-ray; 3.00 A; A/B/C/D=1-531. DR PDB; 6B6U; X-ray; 1.35 A; A/B=7-531. DR PDB; 6GG3; X-ray; 3.72 A; A/B/C/D/E/F/G/H/I/J/K/L=1-531. DR PDB; 6GG4; X-ray; 2.46 A; A/B/C/D=1-531. DR PDB; 6GG5; X-ray; 3.20 A; A/B/C/D=1-531. DR PDB; 6GG6; X-ray; 2.96 A; A/B/C/D/E/F/G/H=1-531. DR PDB; 6JFB; X-ray; 2.12 A; A/B/C/D=1-531. DR PDB; 6NU1; X-ray; 2.25 A; A/B/C/D=1-531. DR PDB; 6NU5; X-ray; 1.60 A; A/B=1-531. DR PDB; 6NUB; X-ray; 1.70 A; A/B=1-531. DR PDB; 6TTF; EM; 3.20 A; A/B/C/D=2-531. DR PDB; 6TTH; EM; 2.60 A; A/B/C/D=2-531. DR PDB; 6TTI; EM; 2.50 A; A/B/C/D=2-531. DR PDB; 6TTQ; EM; 2.70 A; A/B/C/D=2-531. DR PDB; 6V74; X-ray; 2.32 A; A/B/C/D=1-531. DR PDB; 6V75; X-ray; 2.85 A; A/B/C/D=1-531. DR PDB; 6V76; X-ray; 2.75 A; A/B/C/D=1-531. DR PDB; 6WP3; X-ray; 1.84 A; A/B=1-531. DR PDB; 6WP4; X-ray; 1.90 A; A/B/C/D=1-531. DR PDB; 6WP5; X-ray; 2.17 A; A/B/C/D=1-531. DR PDB; 6WP6; X-ray; 2.45 A; A/C=1-531. DR PDB; 7L21; X-ray; 2.29 A; A/B/C/D=1-531. DR PDB; 8G2E; X-ray; 1.84 A; A=1-531. DR PDB; 8HGF; X-ray; 3.10 A; A/B/C/D=1-531. DR PDB; 8HMQ; X-ray; 2.50 A; A/B/C/D=1-531. DR PDB; 8HMR; X-ray; 2.60 A; A/B/C/D=1-531. DR PDB; 8HMS; X-ray; 2.10 A; A/B/C/D=1-531. DR PDB; 8HMU; X-ray; 2.50 A; A/B/C/D=1-531. DR PDB; 8X4R; X-ray; 2.18 A; A/B/C/D=1-531. DR PDB; 9HIA; X-ray; 2.02 A; A/B/C/D=1-531. DR PDB; 9HIB; X-ray; 2.17 A; A/B/C/D=1-531. DR PDB; 9HIC; X-ray; 2.90 A; A/B/C/D=1-531. DR PDB; 9IQQ; X-ray; 2.70 A; A/B/C/D=1-531. DR PDB; 9O3B; X-ray; 2.42 A; A/B/C/D/E/F/G/H=1-531. DR AlphaFoldDB; P14618; -. DR EMDB; EMD-10575; -. DR EMDB; EMD-10576; -. DR EMDB; EMD-10577; -. DR EMDB; EMD-10584; -. DR MDposit; P14618; -. DR MDRepo; P14618; -. DR SMR; P14618; -. DR BioGRID; 111332; 548. DR ComplexPortal; CPX-3057; PKM2 pyruvate kinase complex (dimer). [P14618-1] DR ComplexPortal; CPX-3058; PKM2 pyruvate kinase complex (tetramer). [P14618-1] DR ComplexPortal; CPX-3093; PKM1 pyruvate kinase complex. [P14618-2] DR CORUM; P14618; -. DR DIP; DIP-31273N; -. DR FunCoup; P14618; 1373. DR IntAct; P14618; 337. DR MINT; P14618; -. DR NDEx; IQUERY-CP-PKM; 9 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000320171; -. DR BindingDB; P14618; -. DR ChEMBL; CHEMBL1075189; -. DR DrugBank; DB07697; 1-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)-4-[(4-methoxyphenyl)sulfonyl]piperazine. DR DrugBank; DB07692; 1-[(2,6-difluorophenyl)sulfonyl]-4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl)piperazine. DR DrugBank; DB02726; 2-Phosphoglycolic Acid. DR DrugBank; DB07628; 6-(2-fluorobenzyl)-2,4-dimethyl-4,6-dihydro-5H-thieno[2',3':4,5]pyrrolo[2,3-d]pyridazin-5-one. DR DrugBank; DB00787; Acyclovir. DR DrugBank; DB11638; Artenimol. DR DrugBank; DB09130; Copper. DR DrugBank; DB08951; Indoprofen. DR DrugBank; DB01733; L-Phospholactate. DR DrugBank; DB11263; Polydatin. DR DrugBank; DB00119; Pyruvic acid. DR DrugBank; DB12088; TT-232. DR DrugCentral; P14618; -. DR GuidetoPHARMACOLOGY; 3006; -. DR MoonDB; P14618; Curated. DR MoonProt; P14618; -. DR TCDB; 8.A.261.1.1; the pkm2 pyruvate kinase regulator ({pkm2) family. DR GlyCosmos; P14618; 3 sites, 1 glycan. DR GlyGen; P14618; 7 sites, 1 O-linked glycan (7 sites). DR iPTMnet; P14618; -. DR MetOSite; P14618; -. DR PhosphoSitePlus; P14618; -. DR SwissPalm; P14618; -. DR BioMuta; PKM; -. DR DMDM; 20178296; -. DR OGP; P14618; -. DR REPRODUCTION-2DPAGE; IPI00220644; -. DR REPRODUCTION-2DPAGE; IPI00479186; -. DR CPTAC; CPTAC-2745; -. DR jPOST; P14618; -. DR MassIVE; P14618; -. DR PaxDb; 9606-ENSP00000320171; -. DR PeptideAtlas; P14618; -. DR PRIDE; P14618; -. DR ProteomicsDB; 53065; -. [P14618-3] DR Pumba; P14618; -. DR TopDownProteomics; P14618-1; -. [P14618-1] DR TopDownProteomics; P14618-2; -. [P14618-2] DR Antibodypedia; 14162; 1252 antibodies from 48 providers. DR CPTC; P14618; 1 antibody. DR DNASU; 5315; -. DR Ensembl; ENST00000319622.10; ENSP00000320171.6; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000335181.10; ENSP00000334983.5; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000568459.5; ENSP00000456970.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000891959.1; ENSP00000562018.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000891960.1; ENSP00000562019.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000891961.1; ENSP00000562020.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000891962.1; ENSP00000562021.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000891963.1; ENSP00000562022.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000891964.1; ENSP00000562023.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000891965.1; ENSP00000562024.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000891966.1; ENSP00000562025.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000891967.1; ENSP00000562026.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000891968.1; ENSP00000562027.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000891969.1; ENSP00000562028.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000891970.1; ENSP00000562029.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000891971.1; ENSP00000562030.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000891973.1; ENSP00000562032.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000891974.1; ENSP00000562033.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000891976.1; ENSP00000562035.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000891977.1; ENSP00000562036.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000891979.1; ENSP00000562038.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000891980.1; ENSP00000562039.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000891981.1; ENSP00000562040.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000891982.1; ENSP00000562041.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000891983.1; ENSP00000562042.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000891984.1; ENSP00000562043.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000933438.1; ENSP00000603497.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000933442.1; ENSP00000603501.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000933444.1; ENSP00000603503.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000933446.1; ENSP00000603505.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000969834.1; ENSP00000639893.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000969835.1; ENSP00000639894.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000969836.1; ENSP00000639895.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000969837.1; ENSP00000639896.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000969838.1; ENSP00000639897.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000969839.1; ENSP00000639898.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000969841.1; ENSP00000639900.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000969842.1; ENSP00000639901.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000969843.1; ENSP00000639902.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000969845.1; ENSP00000639904.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000969846.1; ENSP00000639905.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000969847.1; ENSP00000639906.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000969848.1; ENSP00000639907.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000969852.1; ENSP00000639911.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000969853.1; ENSP00000639912.1; ENSG00000067225.22. [P14618-2] DR Ensembl; ENST00000969854.1; ENSP00000639913.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000969855.1; ENSP00000639914.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000969856.1; ENSP00000639915.1; ENSG00000067225.22. [P14618-1] DR Ensembl; ENST00000969857.1; ENSP00000639916.1; ENSG00000067225.22. [P14618-2] DR GeneID; 5315; -. DR KEGG; hsa:5315; -. DR MANE-Select; ENST00000335181.10; ENSP00000334983.5; NM_002654.6; NP_002645.3. DR UCSC; uc002atw.2; human. [P14618-1] DR AGR; HGNC:9021; -. DR ClinPGx; PA33353; -. DR CTD; 5315; -. DR DisGeNET; 5315; -. DR GeneCards; PKM; -. DR HGNC; HGNC:9021; PKM. DR HPA; ENSG00000067225; Tissue enhanced (skeletal muscle, tongue). DR MalaCards; PKM; -. DR MIM; 179050; gene. DR OpenTargets; ENSG00000067225; -. DR VEuPathDB; HostDB:ENSG00000067225; -. DR eggNOG; KOG2323; Eukaryota. DR GeneTree; ENSGT00390000008859; -. DR HOGENOM; CLU_015439_0_1_1; -. DR InParanoid; P14618; -. DR OMA; RVHHIGE; -. DR OrthoDB; 108365at2759; -. DR PAN-GO; P14618; 4 GO annotations based on evolutionary models. DR PhylomeDB; P14618; -. DR BioCyc; MetaCyc:HS00906-MONOMER; -. DR BRENDA; 2.7.1.40; 2681. DR PathwayCommons; P14618; -. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-70171; Glycolysis. DR Reactome; R-HSA-70268; Pyruvate metabolism. DR Reactome; R-HSA-9764725; Negative Regulation of CDH1 Gene Transcription. DR Reactome; R-HSA-9861718; Regulation of pyruvate metabolism. [P14618-1] DR SABIO-RK; P14618; -. DR SignaLink; P14618; -. DR SIGNOR; P14618; -. DR UniPathway; UPA00109; UER00188. DR Agora; ENSG00000067225; -. DR BioGRID-ORCS; 5315; 628 hits in 1182 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; PKM; human. DR EvolutionaryTrace; P14618; -. DR GeneWiki; PKM2; -. DR GenomeRNAi; 5315; -. DR Pharos; P14618; Tchem. DR PRO; PR:P14618; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; P14618; protein. DR Bgee; ENSG00000067225; Expressed in right hemisphere of cerebellum and 208 other cell types or tissues. DR ExpressionAtlas; P14618; baseline and differential. DR GO; GO:0005929; C:cilium; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB. DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005791; C:rough endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome. DR GO; GO:0031982; C:vesicle; HDA:UniProtKB. DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL. DR GO; GO:0035402; F:histone H3T11 kinase activity; IDA:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro. DR GO; GO:0023026; F:MHC class II protein complex binding; HDA:UniProtKB. DR GO; GO:0003729; F:mRNA binding; ISS:UniProtKB. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC. DR GO; GO:0030955; F:potassium ion binding; IEA:InterPro. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-EC. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0004743; F:pyruvate kinase activity; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0061621; P:canonical glycolysis; TAS:Reactome. DR GO; GO:0032869; P:cellular response to insulin stimulus; IBA:GO_Central. DR GO; GO:0006096; P:glycolytic process; IDA:UniProt. DR GO; GO:2000767; P:positive regulation of cytoplasmic translation; ISS:UniProtKB. DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0012501; P:programmed cell death; IDA:UniProtKB. DR GO; GO:0042866; P:pyruvate biosynthetic process; TAS:Reactome. DR CDD; cd00288; Pyruvate_Kinase; 1. DR FunFam; 3.20.20.60:FF:000025; Pyruvate kinase; 1. DR FunFam; 3.40.1380.20:FF:000001; Pyruvate kinase; 1. DR FunFam; 3.40.1380.20:FF:000002; Pyruvate kinase; 1. DR FunFam; 2.40.33.10:FF:000023; Pyruvate kinase PKM; 1. DR Gene3D; 3.20.20.60; Phosphoenolpyruvate-binding domains; 1. DR Gene3D; 2.40.33.10; PK beta-barrel domain-like; 1. DR Gene3D; 3.40.1380.20; Pyruvate kinase, C-terminal domain; 2. DR InterPro; IPR001697; Pyr_Knase. DR InterPro; IPR015813; Pyrv/PenolPyrv_kinase-like_dom. DR InterPro; IPR040442; Pyrv_kinase-like_dom_sf. DR InterPro; IPR011037; Pyrv_Knase-like_insert_dom_sf. DR InterPro; IPR018209; Pyrv_Knase_AS. DR InterPro; IPR015793; Pyrv_Knase_brl. DR InterPro; IPR015795; Pyrv_Knase_C. DR InterPro; IPR036918; Pyrv_Knase_C_sf. DR InterPro; IPR015806; Pyrv_Knase_insert_dom_sf. DR NCBIfam; NF004491; PRK05826.1; 1. DR NCBIfam; NF004978; PRK06354.1; 1. DR NCBIfam; TIGR01064; pyruv_kin; 1. DR PANTHER; PTHR11817; PYRUVATE KINASE; 1. DR Pfam; PF00224; PK; 1. DR Pfam; PF02887; PK_C; 1. DR PRINTS; PR01050; PYRUVTKNASE. DR SUPFAM; SSF51621; Phosphoenolpyruvate/pyruvate domain; 1. DR SUPFAM; SSF50800; PK beta-barrel domain-like; 1. DR SUPFAM; SSF52935; PK C-terminal domain-like; 1. DR PROSITE; PS00110; PYRUVATE_KINASE; 1. DR PDBsum; 1T5A; -. DR PDBsum; 1ZJH; -. DR PDBsum; 3BJF; -. DR PDBsum; 3BJT; -. DR PDBsum; 3G2G; -. DR PDBsum; 3GQY; -. DR PDBsum; 3GR4; -. DR PDBsum; 3H6O; -. DR PDBsum; 3ME3; -. DR PDBsum; 3SRD; -. DR PDBsum; 3SRF; -. DR PDBsum; 3SRH; -. DR PDBsum; 3U2Z; -. DR PDBsum; 4B2D; -. DR PDBsum; 4FXF; -. DR PDBsum; 4FXJ; -. DR PDBsum; 4G1N; -. DR PDBsum; 4JPG; -. DR PDBsum; 4QG6; -. DR PDBsum; 4QG8; -. DR PDBsum; 4QG9; -. DR PDBsum; 4QGC; -. DR PDBsum; 4RPP; -. DR PDBsum; 4WJ8; -. DR PDBsum; 4YJ5; -. DR PDBsum; 5X0I; -. DR PDBsum; 5X1V; -. DR PDBsum; 5X1W; -. DR PDBsum; 6B6U; -. DR PDBsum; 6GG3; -. DR PDBsum; 6GG4; -. DR PDBsum; 6GG5; -. DR PDBsum; 6GG6; -. DR PDBsum; 6JFB; -. DR PDBsum; 6NU1; -. DR PDBsum; 6NU5; -. DR PDBsum; 6NUB; -. DR PDBsum; 6TTF; -. DR PDBsum; 6TTH; -. DR PDBsum; 6TTI; -. DR PDBsum; 6TTQ; -. DR PDBsum; 6V74; -. DR PDBsum; 6V75; -. DR PDBsum; 6V76; -. DR PDBsum; 6WP3; -. DR PDBsum; 6WP4; -. DR PDBsum; 6WP5; -. DR PDBsum; 6WP6; -. DR PDBsum; 7L21; -. DR PDBsum; 8G2E; -. DR PDBsum; 8HGF; -. DR PDBsum; 8HMQ; -. DR PDBsum; 8HMR; -. DR PDBsum; 8HMS; -. DR PDBsum; 8HMU; -. DR PDBsum; 8X4R; -. DR PDBsum; 9HIA; -. DR PDBsum; 9HIB; -. DR PDBsum; 9HIC; -. DR PDBsum; 9IQQ; -. DR PDBsum; 9O3B; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Allosteric enzyme; Alternative splicing; KW ATP-binding; Cytoplasm; Direct protein sequencing; Glycolysis; KW Hydroxylation; Isopeptide bond; Kinase; Magnesium; Metal-binding; KW Methylation; Nucleotide-binding; Nucleus; Phosphoprotein; Potassium; KW Proteomics identification; Pyruvate; Reference proteome; S-nitrosylation; KW Transferase; Translation regulation; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:12665801, FT ECO:0000269|PubMed:1854723, ECO:0000269|Ref.11, FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:25944712" FT CHAIN 2..531 FT /note="Pyruvate kinase PKM" FT /id="PRO_0000112088" FT REGION 307..531 FT /note="Interaction with POU5F1" FT /evidence="ECO:0000269|PubMed:18191611" FT REGION 389..433 FT /note="Intersubunit contact" FT BINDING 70 FT /ligand="L-serine" FT /ligand_id="ChEBI:CHEBI:33384" FT /evidence="ECO:0000269|PubMed:23064226" FT BINDING 73 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P30613" FT BINDING 75..78 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:23530218, FT ECO:0007744|PDB:4FXF" FT BINDING 75 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000269|PubMed:23530218, FT ECO:0007744|PDB:4FXF" FT BINDING 77 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000269|PubMed:23530218, FT ECO:0007744|PDB:4FXF" FT BINDING 106 FT /ligand="L-serine" FT /ligand_id="ChEBI:CHEBI:33384" FT /evidence="ECO:0000269|PubMed:23064226" FT BINDING 113 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000269|PubMed:23530218, FT ECO:0007744|PDB:4FXF" FT BINDING 114 FT /ligand="K(+)" FT /ligand_id="ChEBI:CHEBI:29103" FT /evidence="ECO:0000269|PubMed:23530218, FT ECO:0007744|PDB:4FXF" FT BINDING 120 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:23530218, FT ECO:0007744|PDB:4FXF" FT BINDING 207 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:23530218, FT ECO:0007744|PDB:4FXF" FT BINDING 270 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P30613" FT BINDING 272 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:23530218, FT ECO:0007744|PDB:4FXF" FT BINDING 295 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P30613" FT BINDING 296 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:23530218, FT ECO:0007744|PDB:4FXF" FT BINDING 296 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P30613" FT BINDING 328 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P30613" FT BINDING 432..437 FT /ligand="beta-D-fructose 1,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:32966" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000269|PubMed:15996096, FT ECO:0000269|PubMed:23530218, ECO:0007744|PDB:1T5A, FT ECO:0007744|PDB:4FXF" FT BINDING 464 FT /ligand="L-serine" FT /ligand_id="ChEBI:CHEBI:33384" FT /evidence="ECO:0000269|PubMed:23064226" FT BINDING 482 FT /ligand="beta-D-fructose 1,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:32966" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000269|PubMed:15996096, FT ECO:0000269|PubMed:23530218, ECO:0007744|PDB:1T5A, FT ECO:0007744|PDB:4FXF" FT BINDING 489 FT /ligand="beta-D-fructose 1,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:32966" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000269|PubMed:15996096, FT ECO:0000269|PubMed:23530218, ECO:0007744|PDB:1T5A, FT ECO:0007744|PDB:4FXF" FT BINDING 516..521 FT /ligand="beta-D-fructose 1,6-bisphosphate" FT /ligand_id="ChEBI:CHEBI:32966" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000269|PubMed:15996096, FT ECO:0000269|PubMed:23530218, ECO:0007744|PDB:1T5A, FT ECO:0007744|PDB:4FXF" FT SITE 270 FT /note="Transition state stabilizer" FT /evidence="ECO:0000250|UniProtKB:P00549" FT SITE 433 FT /note="Crucial for phosphotyrosine binding" FT /evidence="ECO:0000269|PubMed:27199445" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000269|Ref.11, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:25944712" FT MOD_RES 3 FT /note="N6,N6,N6-trimethyllysine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 37 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18088087, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 41 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 62 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 66 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P52480" FT MOD_RES 89 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 97 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P11980" FT MOD_RES 100 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P11980" FT MOD_RES 105 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:15592455, FT ECO:0007744|PubMed:23186163" FT MOD_RES 127 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 148 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P52480" FT MOD_RES 166 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 166 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P52480" FT MOD_RES 175 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 195 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 266 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 270 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P52480" FT MOD_RES 305 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:21700219" FT MOD_RES 322 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P52480" FT MOD_RES 322 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P52480" FT MOD_RES 403 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:21620138" FT MOD_RES 408 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:21620138" FT MOD_RES 423 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:30487609" FT MOD_RES 424 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:30487609" FT MOD_RES 433 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:24120661, FT ECO:0000269|PubMed:26787900, ECO:0007744|PubMed:19608861" FT MOD_RES 475 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P52480" FT MOD_RES 498 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P52480" FT CROSSLNK 115 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 166 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 266 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 270 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..82 FT /note="MSKPHSEAGTAFIQTQQLHAAMADTFLEHMCRLDIDSPPITARNTGIICTIG FT PASRSVETLKEMIKSGMNVARLNFSHGTHE -> MSPEAQPQRTKGPQQPCRSPIVKPG FT LPSFRPSSCTQPWLTHSWSTCAAWTLIHHPSQPGTLASSVPL (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043370" FT VAR_SEQ 389..433 FT /note="IYHLQLFEELRRLAPITSDPTEATAVGAVEASFKCCSGAIIVLTK -> MFH FT RKLFEELVRASSHSTDLMEAMAMGSVEASYKCLAAALIVLTE (in isoform M1)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_011101" FT VARIANT 204 FT /note="G -> V (in dbSNP:rs17853396)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_033067" FT MUTAGEN 367 FT /note="K->M: Abolishes both pyruvate kinase and protein FT kinase activities." FT /evidence="ECO:0000269|PubMed:22056988, FT ECO:0000269|PubMed:22901803" FT MUTAGEN 399 FT /note="R->E: Impaired homotetramerization, leading to FT homodimerization and subsequent activation of the protein FT kinase activity." FT /evidence="ECO:0000269|PubMed:22306293" FT MUTAGEN 403 FT /note="P->A: Significant reduction in hydroxylation and in FT PKM-mediated transcriptional activity of HIF1A; when FT associated with A-408." FT /evidence="ECO:0000269|PubMed:21620138" FT MUTAGEN 408 FT /note="P->A: Significant reduction in hydroxylation and in FT PKM-mediated transcriptional activity of HIF1A; when FT associated with A-403." FT /evidence="ECO:0000269|PubMed:21620138" FT MUTAGEN 423..424 FT /note="CC->AA: Abolished S-nitrosylation, leading to FT increased pyruvate kinase activity." FT /evidence="ECO:0000269|PubMed:30487609" FT MUTAGEN 433 FT /note="K->E: Abolished interaction with phosphorylated FT CTNNB1. Impaired phosphorylation of histone H3." FT /evidence="ECO:0000269|PubMed:22056988, FT ECO:0000269|PubMed:22901803" FT MUTAGEN 433 FT /note="K->Q: Mimics acetylation, promoting homodimerization FT and activation of the protein kinase activity." FT /evidence="ECO:0000269|PubMed:24120661, FT ECO:0000269|PubMed:26787900" FT MUTAGEN 433 FT /note="K->R: Abolished acetylation by EP300. Abolished FT deacetylation by SIRT6." FT /evidence="ECO:0000269|PubMed:24120661, FT ECO:0000269|PubMed:26787900" FT MUTAGEN 437 FT /note="S->Y: Unable to bind FBP but still activated by FT serine." FT /evidence="ECO:0000269|PubMed:23064226" FT MUTAGEN 464 FT /note="H->A: Abolishes serine binding and allosteric FT activation." FT /evidence="ECO:0000269|PubMed:23064226" FT CONFLICT 7 FT /note="E -> Q (in Ref. 10; AAH12811)" FT /evidence="ECO:0000305" FT CONFLICT 54 FT /note="A -> T (in Ref. 5; BAG52542)" FT /evidence="ECO:0000305" FT CONFLICT 103 FT /note="I -> Y (in Ref. 2; AAA36672)" FT /evidence="ECO:0000305" FT CONFLICT 132 FT /note="V -> L (in Ref. 2; AAA36672)" FT /evidence="ECO:0000305" FT CONFLICT 187 FT /note="Q -> R (in Ref. 6; BAD96647)" FT /evidence="ECO:0000305" FT CONFLICT 252 FT /note="H -> R (in Ref. 6; BAD96647)" FT /evidence="ECO:0000305" FT CONFLICT 339 FT /note="R -> P (in Ref. 4; CAA39849)" FT /evidence="ECO:0000305" FT CONFLICT 349 FT /note="A -> V (in Ref. 5; BAG52542)" FT /evidence="ECO:0000305" FT CONFLICT 379 FT /note="H -> N (in Ref. 1; AAA36449)" FT /evidence="ECO:0000305" FT CONFLICT 507 FT /note="D -> H (in Ref. 10; AAH12811)" FT /evidence="ECO:0000305" FT HELIX 9..11 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 12..14 FT /evidence="ECO:0007829|PDB:6B6U" FT TURN 15..17 FT /evidence="ECO:0007829|PDB:6V74" FT HELIX 18..21 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 23..25 FT /evidence="ECO:0007829|PDB:6WP4" FT HELIX 26..31 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 35..37 FT /evidence="ECO:0007829|PDB:4QGC" FT HELIX 38..40 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 45..50 FT /evidence="ECO:0007829|PDB:6B6U" FT TURN 53..55 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 58..67 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 71..75 FT /evidence="ECO:0007829|PDB:6B6U" FT TURN 76..78 FT /evidence="ECO:0007829|PDB:6GG6" FT HELIX 81..96 FT /evidence="ECO:0007829|PDB:6B6U" FT TURN 97..100 FT /evidence="ECO:0007829|PDB:6B6U" FT TURN 102..104 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 105..107 FT /evidence="ECO:0007829|PDB:4B2D" FT STRAND 109..113 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 119..121 FT /evidence="ECO:0007829|PDB:6B6U" FT TURN 125..127 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 128..130 FT /evidence="ECO:0007829|PDB:4WJ8" FT STRAND 132..134 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 139..143 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 146..148 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 154..160 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 164..167 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 173..176 FT /evidence="ECO:0007829|PDB:6B6U" FT TURN 177..180 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 181..188 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 190..199 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 201..203 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 204..206 FT /evidence="ECO:0007829|PDB:4B2D" FT STRAND 208..210 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 212..214 FT /evidence="ECO:0007829|PDB:5X1V" FT HELIX 223..234 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 238..242 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 248..257 FT /evidence="ECO:0007829|PDB:6B6U" FT TURN 258..264 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 265..271 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 274..278 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 280..286 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 287..293 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 294..300 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 303..305 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 306..320 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 324..329 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 332..335 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 337..339 FT /evidence="ECO:0007829|PDB:6NU5" FT HELIX 342..354 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 357..362 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 363..366 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 367..369 FT /evidence="ECO:0007829|PDB:1ZJH" FT HELIX 371..388 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 391..400 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 402..404 FT /evidence="ECO:0007829|PDB:6WP6" FT HELIX 408..423 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 428..431 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 433..435 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 436..442 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 450..455 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 457..462 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 463..465 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 469..473 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 477..479 FT /evidence="ECO:0007829|PDB:6B6U" FT HELIX 482..499 FT /evidence="ECO:0007829|PDB:6B6U" FT STRAND 508..512 FT /evidence="ECO:0007829|PDB:6B6U" FT TURN 517..519 FT /evidence="ECO:0007829|PDB:3G2G" FT STRAND 525..529 FT /evidence="ECO:0007829|PDB:6B6U" SQ SEQUENCE 531 AA; 57937 MW; AA94D7818ED6BBAD CRC64; MSKPHSEAGT AFIQTQQLHA AMADTFLEHM CRLDIDSPPI TARNTGIICT IGPASRSVET LKEMIKSGMN VARLNFSHGT HEYHAETIKN VRTATESFAS DPILYRPVAV ALDTKGPEIR TGLIKGSGTA EVELKKGATL KITLDNAYME KCDENILWLD YKNICKVVEV GSKIYVDDGL ISLQVKQKGA DFLVTEVENG GSLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV FASFIRKASD VHEVRKVLGE KGKNIKIISK IENHEGVRRF DEILEASDGI MVARGDLGIE IPAEKVFLAQ KMMIGRCNRA GKPVICATQM LESMIKKPRP TRAEGSDVAN AVLDGADCIM LSGETAKGDY PLEAVRMQHL IAREAEAAIY HLQLFEELRR LAPITSDPTE ATAVGAVEAS FKCCSGAIIV LTKSGRSAHQ VARYRPRAPI IAVTRNPQTA RQAHLYRGIF PVLCKDPVQE AWAEDVDLRV NFAMNVGKAR GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P //