KPYM_HUMAN
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 03-AUG-2022, entry version 264.
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 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 [51]
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 [52]
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 [53]
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 [54]
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 [55]
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 [56]
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 [57]
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:20847263, PubMed:15996096,
CC PubMed:1854723). 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:20847263, PubMed:15996096, PubMed:1854723). 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:20847263, PubMed:15996096, PubMed:1854723).
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). 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 ARNTL/BMAL1-deficient macrophages
CC (By similarity). May also act as a translation regulator for a subset
CC of mRNAs, independently of its pyruvate kinase activity: associates
CC with subpools of endoplasmic reticulum-associated ribosomes, binds
CC directly to the mRNAs translated at the endoplasmic reticulum and
CC promotes 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 -!- 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=ATP + pyruvate = ADP + H(+) + phosphoenolpyruvate;
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=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, 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=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:22901803,
CC 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=ATP + pyruvate = ADP + H(+) + phosphoenolpyruvate;
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:2813362,
CC PubMed:15996096, PubMed:1854723, PubMed:18337815). 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 D-
CC 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:21620138, PubMed:21483450).
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). {ECO:0000269|PubMed:12650930,
CC ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:18191611,
CC ECO:0000269|PubMed:18298799, ECO:0000269|PubMed:18337815,
CC ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:21483450,
CC ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22056988,
CC ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:23064226,
CC ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:25263439,
CC ECO:0000269|PubMed:27199445, ECO:0000269|PubMed:2813362,
CC ECO:0000269|PubMed:32268273}.
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:32268273}. Nucleus {ECO:0000269|PubMed:17308100,
CC ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:22056988,
CC ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661,
CC ECO:0000269|PubMed:26787900, 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;
CC 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: 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=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 and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PKM2ID41728ch15q22.html";
CC ---------------------------------------------------------------------------
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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_001193726.1; NM_001206797.2.
DR RefSeq; NP_001193727.1; NM_001206798.2. [P14618-3]
DR RefSeq; NP_001193728.1; NM_001206799.1.
DR RefSeq; NP_001303247.1; NM_001316318.1.
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_005254445.4. [P14618-1]
DR RefSeq; XP_016877802.1; XM_017022313.1. [P14618-2]
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 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 AlphaFoldDB; P14618; -.
DR SMR; P14618; -.
DR BioGRID; 111332; 371.
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 IntAct; P14618; 295.
DR MINT; P14618; -.
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; DB01733; L-Phospholactate.
DR DrugBank; DB00119; Pyruvic acid.
DR GuidetoPHARMACOLOGY; 3006; -.
DR MoonDB; P14618; Curated.
DR MoonProt; P14618; -.
DR GlyGen; P14618; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; P14618; -.
DR MetOSite; P14618; -.
DR PhosphoSitePlus; P14618; -.
DR SwissPalm; 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 EPD; P14618; -.
DR jPOST; P14618; -.
DR MassIVE; P14618; -.
DR MaxQB; P14618; -.
DR PaxDb; P14618; -.
DR PeptideAtlas; P14618; -.
DR PRIDE; P14618; -.
DR TopDownProteomics; P14618-1; -. [P14618-1]
DR TopDownProteomics; P14618-2; -. [P14618-2]
DR Antibodypedia; 14162; 1257 antibodies from 44 providers.
DR CPTC; P14618; 1 antibody.
DR DNASU; 5315; -.
DR Ensembl; ENST00000319622.10; ENSP00000320171.6; ENSG00000067225.20. [P14618-2]
DR Ensembl; ENST00000335181.10; ENSP00000334983.5; ENSG00000067225.20. [P14618-1]
DR Ensembl; ENST00000568459.5; ENSP00000456970.1; ENSG00000067225.20. [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 CTD; 5315; -.
DR DisGeNET; 5315; -.
DR GeneCards; PKM; -.
DR HGNC; HGNC:9021; PKM.
DR HPA; ENSG00000067225; Tissue enhanced (skeletal muscle, tongue).
DR MIM; 179050; gene.
DR neXtProt; NX_P14618; -.
DR OpenTargets; ENSG00000067225; -.
DR PharmGKB; PA33353; -.
DR VEuPathDB; HostDB:ENSG00000067225; -.
DR eggNOG; KOG2323; Eukaryota.
DR GeneTree; ENSGT00390000008859; -.
DR HOGENOM; CLU_015439_0_1_1; -.
DR InParanoid; P14618; -.
DR OMA; QVPIVQK; -.
DR OrthoDB; 933620at2759; -.
DR PhylomeDB; P14618; -.
DR TreeFam; TF300390; -.
DR BioCyc; MetaCyc:HS00906-MON; -.
DR BRENDA; 2.7.1.40; 2681.
DR PathwayCommons; P14618; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-70171; Glycolysis.
DR SABIO-RK; P14618; -.
DR SignaLink; P14618; -.
DR SIGNOR; P14618; -.
DR UniPathway; UPA00109; UER00188.
DR BioGRID-ORCS; 5315; 605 hits in 1101 CRISPR screens.
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 206 other tissues.
DR ExpressionAtlas; P14618; baseline and differential.
DR Genevisible; P14618; HS.
DR GO; GO:0005929; C:cilium; IEA:Ensembl.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:UniProtKB.
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: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:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0035402; F:histone kinase activity (H3-T11 specific); 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:0030955; F:potassium ion binding; IEA:InterPro.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
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; IEA:Ensembl.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IBA:GO_Central.
DR GO; GO:0006096; P:glycolytic process; IBA:GO_Central.
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 CDD; cd00288; Pyruvate_Kinase; 1.
DR Gene3D; 2.40.33.10; -; 1.
DR Gene3D; 3.20.20.60; -; 1.
DR Gene3D; 3.40.1380.20; -; 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 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; 1.
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; Cytoplasm; Direct protein sequencing; Glycolysis;
KW Hydroxylation; Isopeptide bond; Kinase; Magnesium; Metal-binding;
KW Methylation; Nucleotide-binding; Nucleus; Phosphoprotein; Potassium;
KW Pyruvate; Reference proteome; Transferase; Translation regulation;
KW 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 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 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 ativation 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 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 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 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 TURN 402..404
FT /evidence="ECO:0007829|PDB:3SRF"
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 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
