ID KPYM_HUMAN Reviewed; 531 AA. AC P14618; A6NFK3; B2R5N8; B3KRY0; B4DFX8; B4DUU6; P14786; Q53GK4; AC Q96E76; Q9BWB5; Q9UCV6; Q9UPF2; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 4. DT 09-DEC-2015, entry version 209. DE RecName: Full=Pyruvate kinase PKM; DE EC=2.7.1.40; DE AltName: Full=Cytosolic thyroid hormone-binding protein; DE Short=CTHBP; DE AltName: Full=Opa-interacting protein 3; DE Short=OIP-3; DE AltName: Full=Pyruvate kinase 2/3; DE AltName: Full=Pyruvate kinase muscle isozyme; DE AltName: Full=Thyroid hormone-binding protein 1; DE Short=THBP1; DE AltName: Full=Tumor M2-PK; DE AltName: Full=p58; GN Name=PKM; Synonyms=OIP3, PK2, PK3, PKM2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT and 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 ENZYME 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. 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., RA Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human RT chromosome 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RP 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 RT project: 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 RP METHIONINE, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=B-cell lymphoma; RA Bienvenut W.V.; RL Submitted (JUL-2005) to UniProtKB. RN [12] RP PROTEIN SEQUENCE OF 2-18, CATALYTIC ACTIVITY, ENZYME REGULATION, RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND INTERACTION WITH THYROID RP 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 RT kinase 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., RA Thomas G.R., Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass RT spectrometric 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 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 RT bind pyruvate kinase via their Opa proteins and require host pyruvate RT for growth."; RL Mol. Microbiol. 27:171-186(1998). RN [16] 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 [17] 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 [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105, AND IDENTIFICATION RP BY 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 RT cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION RP BY 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., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION RP BY 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 RT phosphorylation analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [21] 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 [22] RP INTERACTION WITH PML, ENZYME 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 [23] RP INTERACTION WITH POU5F1, IDENTIFICATION BY MASS SPECTROMETRY, RP FUNCTION, 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 RT Oct-4 in regulating transcription."; RL Int. J. Biochem. Cell Biol. 40:1043-1054(2008). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION RP BY 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 [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION RP BY 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 RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION RP BY 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 [27] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37; TYR-175 AND THR-195, RP AND 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 [29] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-62; LYS-89; LYS-166; LYS-266 RP AND LYS-433, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., 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 [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION RP BY 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., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [31] 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., RA Buerckstuemmer T., 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 [32] RP INTERACTION WITH EGLN3 AND HIF1A, SUBCELLULAR LOCATION, INDUCTION, RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, HYDROXYLATION AT RP PRO-403 AND 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- RT inducible factor 1."; RL Cell 145:732-744(2011). RN [33] 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 RT binding to pyruvate kinase."; RL Cell Res. 21:983-986(2011). RN [34] 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., RA Li Z., 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 [35] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [36] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION RP BY 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [37] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., 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 [38] RP X-RAY CRYSTALLOGRAPHY (2.82 ANGSTROMS) OF ISOFORM M2 IN COMPLEX WITH RP OXALATE AND FBP, CATALYTIC ACTIVITY, SUBUNIT, ENZYME MECHANISM, ENZYME RP REGULATION, 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 RT and catalysis."; RL Biochemistry 44:9417-9429(2005). RN [39] 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 [40] RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 14-531 ALONE AND IN COMPLEX RP WITH FBP, AND ENZYME 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 [41] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 2-531, ENZYME REGULATION BY RP SERINE, MAGNESIUM-BINDING SITES, SUBUNIT, AND MUTAGENESIS OF SER-437 RP AND 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., RA Vousden K.H., Frezza C., O'Reilly M., Gottlieb E.; RT "Serine is a natural ligand and allosteric activator of pyruvate RT kinase M2."; RL Nature 491:458-462(2012). RN [42] 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: Glycolytic enzyme that catalyzes the transfer of a CC phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating CC ATP. Stimulates POU5F1-mediated transcriptional activation. Plays CC a general role in caspase independent cell death of tumor cells. CC The ratio betwween the highly active tetrameric form and nearly CC inactive dimeric form determines whether glucose carbons are CC channeled to biosynthetic processes or used for glycolytic ATP CC production. The transition between the 2 forms contributes to the CC control of glycolysis and is important for tumor cell CC proliferation and survival. {ECO:0000269|PubMed:17308100, CC ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:21620138}. CC -!- CATALYTIC ACTIVITY: ATP + pyruvate = ADP + phosphoenolpyruvate. CC {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723}. 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 -!- ENZYME REGULATION: Isoform M2 is allosterically activated by D- CC fructose 1,6-bisphosphate (FBP). Inhibited by oxalate and 3,3',5- CC triiodo-L-thyronine (T3). The activity of the tetrameric form is CC inhibited by PML. Selective binding to tyrosine-phosphorylated CC peptides releases the allosteric activator FBP, leading to CC inhibition of PKM enzymatic activity, this diverts glucose CC metabolites from energy production to anabolic processes when CC cells are stimulated by certain growth factors. Glycolytic flux CC are highly dependent on de novo biosynthesis of serine and CC glycine, and serine is a natural ligand and allosteric activator CC of isoform M2. {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:2813362}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=2.7 mM for phosphoenolpyruvate (at 32 degrees Celsius, pH CC 8.0) {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723}; CC KM=0.17 mM for phosphoenolpyruvate (in the presence of 2 mM FBP, CC at 32 degrees Celsius, pH 8.0) {ECO:0000269|PubMed:15996096, CC 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, CC at 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, CC 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. CC -!- SUBUNIT: Monomer and homotetramer. Exists as a monomer in the CC absence of FBP, and reversibly associates to form a homotetramer CC in the presence of FBP. The monomeric form binds T3. Tetramer CC formation induces pyruvate kinase activity. The tetrameric form CC has high affinity for the substrate and is associated within the CC glycolytic enzyme complex. Exists in a nearly inactive dimeric CC form in tumor cells and the dimeric form has less affinity for the CC substrate. Binding to certain oncoproteins such as HPV-16 E7 CC oncoprotein can trigger dimerization. FBP stimulates the formation CC of tetramers from dimers. Interacts with HERC1, POU5F1 and PML. CC Interacts (isoform M2) with EGLN3; the interaction hydroxylates CC PKM under hypoxia and enhances binding to HIF1A. Interacts CC (isoform M2) with HIF1A; the interaction is enhanced by binding of CC EGLN3, promoting enhanced transcription activity under hypoxia. 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:23064226, ECO:0000269|PubMed:2813362}. CC -!- INTERACTION: CC Q9WMX2:- (xeno); NbExp=4; IntAct=EBI-353408, EBI-710918; CC P10398:ARAF; NbExp=2; IntAct=EBI-353408, EBI-365961; CC P49407:ARRB1; NbExp=3; IntAct=EBI-353408, EBI-743313; CC P32121:ARRB2; NbExp=4; IntAct=EBI-353408, EBI-714559; CC P53355:DAPK1; NbExp=3; IntAct=EBI-353408, EBI-358616; CC Q9H6Z9:EGLN3; NbExp=2; IntAct=EBI-4304679, EBI-1175354; CC Q16665:HIF1A; NbExp=7; IntAct=EBI-4304679, EBI-447269; CC P68431:HIST1H3J; NbExp=3; IntAct=EBI-4304679, EBI-79722; CC P42858:HTT; NbExp=3; IntAct=EBI-353408, EBI-466029; CC P27361:MAPK3; NbExp=3; IntAct=EBI-4304679, EBI-73995; CC P04049:RAF1; NbExp=3; IntAct=EBI-353408, EBI-365996; CC Q9BSI4:TINF2; NbExp=2; IntAct=EBI-353408, EBI-717399; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocates to the CC nucleus in response to different apoptotic stimuli. Nuclear CC translocation is sufficient to induce cell death that is caspase CC independent, isoform-specific and independent of its enzymatic CC activity. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=M2; Synonyms=M2-PK, PKM2; CC IsoId=P14618-1; Sequence=Displayed; CC Name=M1; Synonyms=M1-PK, PKM1; CC IsoId=P14618-2, P14786-1; CC Sequence=VSP_011101; CC Name=3; CC IsoId=P14618-3; Sequence=VSP_043370; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Specifically expressed in proliferating cells, CC such as embryonic stem cells, embryonic carcinoma cells, as well CC as cancer cells. {ECO:0000269|PubMed:18191611}. 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 CC lysosomal-dependent degradation via chaperone-mediated autophagy. CC {ECO:0000269|PubMed:21700219, ECO:0000269|Ref.11}. CC -!- MISCELLANEOUS: There are 4 isozymes of pyruvate kinase in mammals CC (L, R, M1, M2) encoded by 2 different genes: PKLR and PKM. The L CC and R isozymes are generated from the PKLR by differential CC splicing of RNA; the M1 and M2 forms are produced from the PKM CC gene by differential splicing. L type is major isozyme in the CC liver, R is found in red cells, M1 is the main form in muscle, CC heart and brain, and M2 is found in early fetal tissues as well as CC 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=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/pkm2/"; 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 CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/PKM2ID41728ch15q22.html"; 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 CCDS; CCDS55972.1; -. [P14618-3] DR PIR; S30038; S30038. DR PIR; S64635; S64635. DR RefSeq; NP_001193725.1; NM_001206796.2. DR RefSeq; NP_001193727.1; NM_001206798.2. [P14618-3] DR RefSeq; NP_001193728.1; NM_001206799.1. DR RefSeq; NP_002645.3; NM_002654.5. [P14618-1] DR RefSeq; NP_872270.1; NM_182470.3. [P14618-2] DR RefSeq; NP_872271.1; NM_182471.3. [P14618-2] DR RefSeq; XP_005254502.1; XM_005254445.3. [P14618-1] DR UniGene; Hs.534770; -. DR UniGene; Hs.704299; -. 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 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 ProteinModelPortal; P14618; -. DR SMR; P14618; 13-531. DR BioGrid; 111332; 160. DR DIP; DIP-31273N; -. DR IntAct; P14618; 236. DR MINT; MINT-4998892; -. DR STRING; 9606.ENSP00000320171; -. DR BindingDB; P14618; -. DR ChEMBL; CHEMBL1075189; -. DR DrugBank; DB00119; Pyruvic acid. DR PhosphoSite; P14618; -. DR BioMuta; PKM; -. DR DMDM; 20178296; -. DR DOSAC-COBS-2DPAGE; P14618; -. DR OGP; P14618; -. DR REPRODUCTION-2DPAGE; IPI00220644; -. DR REPRODUCTION-2DPAGE; IPI00479186; -. DR UCD-2DPAGE; P14618; -. DR MaxQB; P14618; -. DR PaxDb; P14618; -. DR PRIDE; P14618; -. DR DNASU; 5315; -. DR Ensembl; ENST00000319622; ENSP00000320171; ENSG00000067225. [P14618-2] DR Ensembl; ENST00000335181; ENSP00000334983; ENSG00000067225. [P14618-1] DR Ensembl; ENST00000449901; ENSP00000403365; ENSG00000067225. [P14618-3] DR Ensembl; ENST00000565154; ENSP00000455901; ENSG00000067225. [P14618-2] DR Ensembl; ENST00000565184; ENSP00000455736; ENSG00000067225. [P14618-2] DR Ensembl; ENST00000568459; ENSP00000456970; ENSG00000067225. [P14618-2] DR GeneID; 5315; -. DR KEGG; hsa:5315; -. DR UCSC; uc002atv.2; human. [P14618-2] DR UCSC; uc002aty.2; human. [P14618-1] DR UCSC; uc010ukj.2; human. [P14618-3] DR CTD; 5315; -. DR GeneCards; PKM; -. DR HGNC; HGNC:9021; PKM. DR HPA; CAB019421; -. DR HPA; HPA029501; -. DR MIM; 179050; gene. DR neXtProt; NX_P14618; -. DR PharmGKB; PA33353; -. DR eggNOG; KOG2323; Eukaryota. DR eggNOG; COG0469; LUCA. DR GeneTree; ENSGT00390000008859; -. DR HOGENOM; HOG000021559; -. DR HOVERGEN; HBG000941; -. DR InParanoid; P14618; -. DR KO; K00873; -. DR OMA; DMQDARQ; -. DR OrthoDB; EOG78M01Q; -. DR PhylomeDB; P14618; -. DR TreeFam; TF300390; -. DR BioCyc; MetaCyc:HS00906-MONOMER; -. DR BRENDA; 2.7.1.40; 2681. DR Reactome; R-HSA-70171; Glycolysis. DR SABIO-RK; P14618; -. DR UniPathway; UPA00109; UER00188. DR EvolutionaryTrace; P14618; -. DR GeneWiki; PKM2; -. DR GenomeRNAi; 5315; -. DR NextBio; 20554; -. DR PRO; PR:P14618; -. DR Proteomes; UP000005640; Chromosome 15. DR Bgee; P14618; -. DR CleanEx; HS_PKM2; -. DR ExpressionAtlas; P14618; baseline and differential. DR Genevisible; P14618; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; NAS:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB. DR GO; GO:1903561; C:extracellular vesicle; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0031982; C:vesicle; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW. DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro. DR GO; GO:0023026; F:MHC class II protein complex binding; IDA:UniProtKB. DR GO; GO:0044822; F:poly(A) RNA binding; IDA:UniProtKB. DR GO; GO:0030955; F:potassium ion binding; IEA:InterPro. DR GO; GO:0004743; F:pyruvate kinase activity; TAS:UniProtKB. DR GO; GO:0061621; P:canonical glycolysis; TAS:Reactome. DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:Reactome. DR GO; GO:0006006; P:glucose metabolic process; TAS:Reactome. DR GO; GO:0012501; P:programmed cell death; IDA:UniProtKB. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR Gene3D; 2.40.33.10; -; 1. DR Gene3D; 3.20.20.60; -; 2. DR Gene3D; 3.40.1380.20; -; 1. DR InterPro; IPR001697; Pyr_Knase. DR InterPro; IPR015813; Pyrv/PenolPyrv_Kinase-like_dom. DR InterPro; IPR011037; Pyrv_Knase-like_insert_dom. DR InterPro; IPR015794; Pyrv_Knase_a/b. DR InterPro; IPR018209; Pyrv_Knase_AS. DR InterPro; IPR015793; Pyrv_Knase_brl. DR InterPro; IPR015795; Pyrv_Knase_C. DR InterPro; IPR015806; Pyrv_Knase_insert_dom. DR PANTHER; PTHR11817; PTHR11817; 1. DR Pfam; PF00224; PK; 1. DR Pfam; PF02887; PK_C; 1. DR PRINTS; PR01050; PYRUVTKNASE. DR SUPFAM; SSF50800; SSF50800; 1. DR SUPFAM; SSF51621; SSF51621; 2. DR SUPFAM; SSF52935; SSF52935; 1. DR TIGRFAMs; TIGR01064; pyruv_kin; 1. DR PROSITE; PS00110; PYRUVATE_KINASE; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Allosteric enzyme; Alternative splicing; KW ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; KW Glycolysis; Hydroxylation; Kinase; Magnesium; Metal-binding; KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Potassium; KW Pyruvate; Reference proteome; Transferase; Ubl conjugation. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:25944712, FT ECO:0000269|PubMed:12665801, FT ECO:0000269|PubMed:1854723, FT ECO:0000269|Ref.11}. FT CHAIN 2 531 Pyruvate kinase PKM. FT /FTId=PRO_0000112088. FT NP_BIND 75 78 ATP. {ECO:0000244|PDB:4FXF, FT ECO:0000269|PubMed:23530218}. FT REGION 307 531 Interaction with POU5F1. FT REGION 389 433 Intersubunit contact. FT REGION 432 437 D-fructose 1,6-bisphosphate binding; part FT of allosteric site. FT {ECO:0000244|PDB:1T5A, FT ECO:0000244|PDB:4FXF, FT ECO:0000269|PubMed:15996096, FT ECO:0000269|PubMed:23530218}. FT REGION 516 521 D-fructose 1,6-bisphosphate binding; part FT of allosteric site. FT {ECO:0000244|PDB:1T5A, FT ECO:0000244|PDB:4FXF, FT ECO:0000269|PubMed:15996096, FT ECO:0000269|PubMed:23530218}. FT METAL 75 75 Potassium. {ECO:0000244|PDB:4FXF, FT ECO:0000269|PubMed:23530218}. FT METAL 77 77 Potassium. {ECO:0000244|PDB:4FXF, FT ECO:0000269|PubMed:23530218}. FT METAL 113 113 Potassium. {ECO:0000244|PDB:4FXF, FT ECO:0000269|PubMed:23530218}. FT METAL 114 114 Potassium; via carbonyl oxygen. FT {ECO:0000244|PDB:4FXF, FT ECO:0000269|PubMed:23530218}. FT METAL 272 272 Magnesium. {ECO:0000244|PDB:4FXF, FT ECO:0000269|PubMed:23530218}. FT METAL 296 296 Magnesium. {ECO:0000244|PDB:4FXF, FT ECO:0000269|PubMed:23530218}. FT BINDING 70 70 Serine. FT BINDING 73 73 Substrate. FT {ECO:0000250|UniProtKB:P30613}. FT BINDING 106 106 Serine. FT BINDING 120 120 ATP. {ECO:0000244|PDB:4FXF, FT ECO:0000269|PubMed:23530218}. FT BINDING 207 207 ATP. {ECO:0000244|PDB:4FXF, FT ECO:0000269|PubMed:23530218}. FT BINDING 270 270 Substrate; via amide nitrogen. FT {ECO:0000250|UniProtKB:P30613}. FT BINDING 295 295 Substrate; via amide nitrogen. FT {ECO:0000250|UniProtKB:P30613}. FT BINDING 296 296 Substrate; via amide nitrogen. FT {ECO:0000250|UniProtKB:P30613}. FT BINDING 328 328 Substrate. FT {ECO:0000250|UniProtKB:P30613}. FT BINDING 464 464 Serine. FT BINDING 482 482 D-fructose 1,6-bisphosphate; part of FT allosteric site. {ECO:0000244|PDB:1T5A, FT ECO:0000244|PDB:4FXF, FT ECO:0000269|PubMed:15996096, FT ECO:0000269|PubMed:23530218}. FT BINDING 489 489 D-fructose 1,6-bisphosphate; part of FT allosteric site. {ECO:0000244|PDB:1T5A, FT ECO:0000244|PDB:4FXF, FT ECO:0000269|PubMed:15996096, FT ECO:0000269|PubMed:23530218}. FT SITE 270 270 Transition state stabilizer. FT {ECO:0000250|UniProtKB:P00549}. FT SITE 433 433 Crucial for phosphotyrosine binding. FT MOD_RES 2 2 N-acetylserine. FT {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:25944712, FT ECO:0000269|Ref.11}. FT MOD_RES 37 37 Phosphoserine. FT {ECO:0000244|PubMed:16964243, FT ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:18088087, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 62 62 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 66 66 N6-succinyllysine. FT {ECO:0000250|UniProtKB:P52480}. FT MOD_RES 89 89 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 97 97 Phosphoserine. FT {ECO:0000250|UniProtKB:P11980}. FT MOD_RES 100 100 Phosphoserine. FT {ECO:0000250|UniProtKB:P11980}. FT MOD_RES 105 105 Phosphotyrosine. FT {ECO:0000244|PubMed:15592455}. FT MOD_RES 148 148 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P52480}. FT MOD_RES 166 166 N6-acetyllysine; alternate. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 166 166 N6-succinyllysine; alternate. FT {ECO:0000250|UniProtKB:P52480}. FT MOD_RES 175 175 Phosphotyrosine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 195 195 Phosphothreonine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 249 249 Phosphoserine. FT {ECO:0000250|UniProtKB:P30613}. FT MOD_RES 266 266 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 270 270 N6-acetyllysine. FT {ECO:0000250|UniProtKB:P52480}. FT MOD_RES 305 305 N6-acetyllysine. FT {ECO:0000269|PubMed:21700219}. FT MOD_RES 322 322 N6-acetyllysine; alternate. FT {ECO:0000250|UniProtKB:P52480}. FT MOD_RES 322 322 N6-succinyllysine; alternate. FT {ECO:0000250|UniProtKB:P52480}. FT MOD_RES 403 403 4-hydroxyproline. FT {ECO:0000269|PubMed:21620138}. FT MOD_RES 408 408 4-hydroxyproline. FT {ECO:0000269|PubMed:21620138}. FT MOD_RES 433 433 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 475 475 N6-acetyllysine. FT {ECO:0000250|UniProtKB:P52480}. FT MOD_RES 498 498 N6-succinyllysine. FT {ECO:0000250|UniProtKB:P52480}. FT VAR_SEQ 1 82 MSKPHSEAGTAFIQTQQLHAAMADTFLEHMCRLDIDSPPIT FT ARNTGIICTIGPASRSVETLKEMIKSGMNVARLNFSHGTHE FT -> MSPEAQPQRTKGPQQPCRSPIVKPGLPSFRPSSCTQPW FT LTHSWSTCAAWTLIHHPSQPGTLASSVPL (in isoform FT 3). {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_043370. FT VAR_SEQ 389 433 IYHLQLFEELRRLAPITSDPTEATAVGAVEASFKCCSGAII FT VLTK -> MFHRKLFEELVRASSHSTDLMEAMAMGSVEASY FT KCLAAALIVLTE (in isoform M1). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_011101. FT VARIANT 204 204 G -> V (in dbSNP:rs17853396). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_033067. FT MUTAGEN 403 403 P->A: Significant reduction in FT hydroxylation and in PKM-mediated FT transcriptional activity of HIF1A; when FT associated with A-408. FT {ECO:0000269|PubMed:21620138}. FT MUTAGEN 408 408 P->A: Significant reduction in FT hydroxylation and in PKM-mediated FT transcriptional activity of HIF1A; when FT associated with A-403. FT {ECO:0000269|PubMed:21620138}. FT MUTAGEN 437 437 S->Y: Unable to bind FBP but still FT activated by serine. FT {ECO:0000269|PubMed:23064226}. FT MUTAGEN 464 464 H->A: Abolishes serine binding and FT allosteric activation. FT {ECO:0000269|PubMed:23064226}. FT CONFLICT 7 7 E -> Q (in Ref. 10; AAH12811). FT {ECO:0000305}. FT CONFLICT 54 54 A -> T (in Ref. 5; BAG52542). FT {ECO:0000305}. FT CONFLICT 103 103 I -> Y (in Ref. 2; AAA36672). FT {ECO:0000305}. FT CONFLICT 132 132 V -> L (in Ref. 2; AAA36672). FT {ECO:0000305}. FT CONFLICT 187 187 Q -> R (in Ref. 6; BAD96647). FT {ECO:0000305}. FT CONFLICT 252 252 H -> R (in Ref. 6; BAD96647). FT {ECO:0000305}. FT CONFLICT 339 339 R -> P (in Ref. 4; CAA39849). FT {ECO:0000305}. FT CONFLICT 349 349 A -> V (in Ref. 5; BAG52542). FT {ECO:0000305}. FT CONFLICT 379 379 H -> N (in Ref. 1; AAA36449). FT {ECO:0000305}. FT CONFLICT 507 507 D -> H (in Ref. 10; AAH12811). FT {ECO:0000305}. FT HELIX 15 17 {ECO:0000244|PDB:3SRD}. FT HELIX 18 21 {ECO:0000244|PDB:3GR4}. FT HELIX 26 31 {ECO:0000244|PDB:3GR4}. FT STRAND 35 37 {ECO:0000244|PDB:4QGC}. FT STRAND 45 50 {ECO:0000244|PDB:3GR4}. FT TURN 53 55 {ECO:0000244|PDB:3GR4}. FT HELIX 58 67 {ECO:0000244|PDB:3GR4}. FT STRAND 71 75 {ECO:0000244|PDB:3GR4}. FT HELIX 76 78 {ECO:0000244|PDB:4QG6}. FT HELIX 81 96 {ECO:0000244|PDB:3GR4}. FT TURN 97 100 {ECO:0000244|PDB:3GR4}. FT TURN 102 104 {ECO:0000244|PDB:3GR4}. FT STRAND 109 113 {ECO:0000244|PDB:3GR4}. FT STRAND 119 121 {ECO:0000244|PDB:3ME3}. FT STRAND 127 129 {ECO:0000244|PDB:3GQY}. FT STRAND 132 134 {ECO:0000244|PDB:3GR4}. FT STRAND 139 143 {ECO:0000244|PDB:3GR4}. FT HELIX 146 148 {ECO:0000244|PDB:3GR4}. FT STRAND 154 160 {ECO:0000244|PDB:3GR4}. FT HELIX 164 167 {ECO:0000244|PDB:3GR4}. FT STRAND 173 176 {ECO:0000244|PDB:3GR4}. FT TURN 177 180 {ECO:0000244|PDB:3GR4}. FT STRAND 181 188 {ECO:0000244|PDB:3GR4}. FT STRAND 190 199 {ECO:0000244|PDB:3GR4}. FT STRAND 201 203 {ECO:0000244|PDB:3GR4}. FT STRAND 204 206 {ECO:0000244|PDB:4B2D}. FT STRAND 208 210 {ECO:0000244|PDB:3GR4}. FT STRAND 212 214 {ECO:0000244|PDB:4JPG}. FT HELIX 223 234 {ECO:0000244|PDB:3GR4}. FT STRAND 238 242 {ECO:0000244|PDB:3GR4}. FT HELIX 248 258 {ECO:0000244|PDB:3GR4}. FT TURN 259 264 {ECO:0000244|PDB:3GR4}. FT STRAND 265 271 {ECO:0000244|PDB:3GR4}. FT HELIX 274 278 {ECO:0000244|PDB:3GR4}. FT HELIX 280 286 {ECO:0000244|PDB:3GR4}. FT STRAND 287 293 {ECO:0000244|PDB:3GR4}. FT HELIX 294 300 {ECO:0000244|PDB:3GR4}. FT HELIX 303 305 {ECO:0000244|PDB:3GR4}. FT HELIX 306 320 {ECO:0000244|PDB:3GR4}. FT STRAND 324 329 {ECO:0000244|PDB:3GR4}. FT HELIX 332 335 {ECO:0000244|PDB:3GR4}. FT STRAND 337 339 {ECO:0000244|PDB:3BJT}. FT HELIX 342 354 {ECO:0000244|PDB:3GR4}. FT STRAND 357 362 {ECO:0000244|PDB:3GR4}. FT HELIX 363 366 {ECO:0000244|PDB:3GR4}. FT STRAND 367 369 {ECO:0000244|PDB:1ZJH}. FT HELIX 371 387 {ECO:0000244|PDB:3GR4}. FT HELIX 391 401 {ECO:0000244|PDB:3GR4}. FT TURN 402 404 {ECO:0000244|PDB:3SRF}. FT HELIX 408 422 {ECO:0000244|PDB:3GR4}. FT STRAND 428 431 {ECO:0000244|PDB:3GR4}. FT STRAND 433 435 {ECO:0000244|PDB:3GR4}. FT HELIX 436 442 {ECO:0000244|PDB:3GR4}. FT STRAND 450 455 {ECO:0000244|PDB:3GR4}. FT HELIX 457 462 {ECO:0000244|PDB:3GR4}. FT HELIX 463 465 {ECO:0000244|PDB:3GR4}. FT STRAND 469 473 {ECO:0000244|PDB:3GR4}. FT HELIX 482 499 {ECO:0000244|PDB:3GR4}. FT STRAND 508 518 {ECO:0000244|PDB:3GR4}. FT STRAND 522 529 {ECO:0000244|PDB:3GR4}. 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 //