KPYM_MOUSE
ID KPYM_MOUSE Reviewed; 531 AA.
AC P52480; Q3TBV8; Q3TBW5; Q3TC59; Q3U1X3; Q3U5P6; Q4VC20; Q64484; Q91YI8;
AC Q9CWB1;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 4.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Pyruvate kinase PKM;
DE EC=2.7.1.40 {ECO:0000250|UniProtKB:P14618};
DE AltName: Full=Pyruvate kinase muscle isozyme;
DE AltName: Full=Threonine-protein kinase PKM2 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P14618};
DE AltName: Full=Tyrosine-protein kinase PKM2 {ECO:0000305};
DE EC=2.7.10.2 {ECO:0000250|UniProtKB:P14618};
GN Name=Pkm; Synonyms=Pk3, Pkm2, Pykm;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M2).
RX PubMed=7612666; DOI=10.1016/0167-4889(95)00071-y;
RA Izumi S., Manabe A., Tomoyasu A., Kihara-Negishi F., Ariga H.;
RT "Molecular cloning of the complementary DNA for the mouse pyruvate kinase
RT M-2 gene whose expression is dependent upon cell differentiation.";
RL Biochim. Biophys. Acta 1267:135-138(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM M2).
RC STRAIN=SWR/J;
RX PubMed=9545585; DOI=10.1016/s0167-4781(97)00195-4;
RA de Luis O., del Mazo J.;
RT "Gene expression of mouse M1 and M2 pyruvate kinase isoenzymes correlates
RT with differential poly(A) tract extension of their mRNAs during the
RT development of spermatogenesis.";
RL Biochim. Biophys. Acta 1396:294-305(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM M2), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1-395 (ISOFORM M1).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow, Kidney, and Muellerian duct;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM M2).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Mammary tumor;
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 [6]
RP PROTEIN SEQUENCE OF 33-56; 67-89; 93-115; 126-136; 142-162; 167-224;
RP 231-246; 248-255; 279-305; 320-336; 343-399; 401-433; 468-498 AND 506-526,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J, and OF1; TISSUE=Brain, and Hippocampus;
RA Lubec G., Kang S.U., Klug S., Yang J.W., Zigmond M., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [7]
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 [8]
RP 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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-105 AND TYR-148, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-62; LYS-166; LYS-270; LYS-322 AND
RP LYS-475, SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-66; LYS-166; LYS-322
RP AND LYS-498, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [12]
RP FUNCTION, AND MUTAGENESIS OF LYS-367 AND HIS-464.
RX PubMed=28575669; DOI=10.1016/j.cell.2017.05.022;
RA Simsek D., Tiu G.C., Flynn R.A., Byeon G.W., Leppek K., Xu A.F.,
RA Chang H.Y., Barna M.;
RT "The mammalian ribo-interactome reveals ribosome functional diversity and
RT heterogeneity.";
RL Cell 169:1051-1065(2017).
RN [13]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29996098; DOI=10.1016/j.celrep.2018.06.026;
RA Deng W., Zhu S., Zeng L., Liu J., Kang R., Yang M., Cao L., Wang H.,
RA Billiar T.R., Jiang J., Xie M., Tang D.;
RT "The circadian clock controls immune checkpoint pathway in sepsis.";
RL Cell Rep. 24:366-378(2018).
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. The ratio between the highly active
CC tetrameric form and nearly inactive dimeric form determines whether
CC glucose carbons are channeled to biosynthetic processes or used for
CC glycolytic ATP production. The transition between the 2 forms
CC contributes to the control of glycolysis and is important for tumor
CC cell proliferation and survival. {ECO:0000250|UniProtKB:P14618}.
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 (By similarity). In addition to its pyruvate
CC kinase activity in the cytoplasm, also acts as a regulator of
CC transcription in the nucleus by acting as a protein kinase (By
CC similarity). Translocates into the nucleus in response to various
CC signals, such as EGF receptor activation, and homodimerizes, leading to
CC its conversion into a protein threonine- and tyrosine-protein kinase
CC (By similarity). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and
CC histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (By
CC similarity). Its ability to activate transcription plays a role in
CC cancer cells by promoting cell proliferation and promote tumorigenesis
CC (By similarity). Promotes the expression of the immune checkpoint
CC protein CD274 in ARNTL/BMAL1-deficient macrophages (PubMed:29996098).
CC May also act as a translation regulator for a subset of mRNAs,
CC independently of its pyruvate kinase activity: associates with subpools
CC of endoplasmic reticulum-associated ribosomes, binds directly to the
CC mRNAs translated at the endoplasmic reticulum and promotes translation
CC of these endoplasmic reticulum-destined mRNAs (PubMed:28575669). Plays
CC a role in caspase independent cell death of tumor cells (By
CC similarity). {ECO:0000250|UniProtKB:P14618,
CC ECO:0000269|PubMed:28575669, ECO:0000269|PubMed:29996098}.
CC -!- FUNCTION: [Isoform M1]: Pyruvate kinase isoform expressed in adult
CC tissues, which replaces isoform M2 after birth. In contrast to isoform
CC M2, has high pyruvate kinase activity by itself and does not require
CC allosteric activation by D-fructose 1,6-bisphosphate (FBP) for
CC activity. {ECO:0000250|UniProtKB:P14618}.
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:0000250|UniProtKB:P14618};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18159;
CC Evidence={ECO:0000250|UniProtKB:P14618};
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:0000250|UniProtKB:P14618};
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:0000250|UniProtKB:P14618};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10597;
CC Evidence={ECO:0000250|UniProtKB:P14618};
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:0000250|UniProtKB:P14618};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000250|UniProtKB:P14618};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P14618};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
CC Evidence={ECO:0000250|UniProtKB:P14618};
CC -!- ACTIVITY REGULATION: [Isoform M2]: Isoform M2 is allosterically
CC activated by D-fructose 1,6-bisphosphate (FBP). Inhibited by oxalate
CC and 3,3',5-triiodo-L-thyronine (T3). The activity of the tetrameric
CC form is inhibited by PML. Selective binding to tyrosine-phosphorylated
CC peptides releases the allosteric activator FBP, leading to inhibition
CC of PKM enzymatic activity, this diverts glucose metabolites from energy
CC production to anabolic processes when cells are stimulated by certain
CC growth factors. 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. Acetylation at Lys-433 promotes its
CC translocation into the nucleus and homodimerization, promoting the
CC protein kinase activity. {ECO:0000250|UniProtKB:P14618}.
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:0000250|UniProtKB:P14618}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-
CC glyceraldehyde 3-phosphate: step 5/5. {ECO:0000250|UniProtKB:P14618}.
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. The monomeric
CC form binds 3,3',5-triiodo-L-thyronine (T3). Tetramer formation induces
CC pyruvate kinase activity. The tetrameric form has high affinity for the
CC substrate and is associated within the glycolytic enzyme complex. FBP
CC stimulates the formation of tetramers from dimers. Homodimer; exists in
CC a dimeric form in tumor cells and the dimeric form has less affinity
CC for the phosphoenolpyruvate substrate. The homodimer converts into a
CC protein kinase. Interacts with HERC1, POU5F1 and PML. Interacts with
CC EGLN3; the interaction hydroxylates PKM under hypoxia and enhances
CC binding to HIF1A. Interacts with HIF1A; the interaction is enhanced by
CC binding of EGLN3, promoting enhanced transcription activity under
CC hypoxia. Interacts with TRIM35; this interaction prevents FGFR1-
CC dependent tyrosine phosphorylation. Interacts with JMJD8. Interacts
CC with TRAF4. Interacts with (phosphorylated) CTNNB1; leading to activate
CC transcription. {ECO:0000250|UniProtKB:P14618}.
CC -!- INTERACTION:
CC P52480; P20263: Pou5f1; NbExp=6; IntAct=EBI-647785, EBI-1606219;
CC P52480; PRO_0000025675 [P04156]: PRNP; Xeno; NbExp=5; IntAct=EBI-647785, EBI-8830282;
CC P52480; P26663; Xeno; NbExp=3; IntAct=EBI-647785, EBI-6857429;
CC -!- SUBCELLULAR LOCATION: [Isoform M2]: Cytoplasm
CC {ECO:0000250|UniProtKB:P14618}. Nucleus {ECO:0000250|UniProtKB:P14618}.
CC Note=Translocates to the nucleus in response to various signals, such
CC as EGF receptor activation or apoptotic stimuli. Nuclear translocation
CC is promoted by acetylation by EP300. 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 {ECO:0000250|UniProtKB:P14618}.
CC -!- SUBCELLULAR LOCATION: [Isoform M1]: Cytoplasm
CC {ECO:0000250|UniProtKB:P14618}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=M2 {ECO:0000303|PubMed:28575669}; Synonyms=PKM2
CC {ECO:0000303|PubMed:28575669};
CC IsoId=P52480-1; Sequence=Displayed;
CC Name=M1 {ECO:0000303|PubMed:28575669}; Synonyms=PKM1
CC {ECO:0000303|PubMed:28575669};
CC IsoId=P52480-2; Sequence=VSP_025057;
CC -!- TISSUE SPECIFICITY: Embryonic stem cells and embryonal carcinoma cells.
CC {ECO:0000269|PubMed:18191611}.
CC -!- PTM: ISGylated. {ECO:0000269|PubMed:16139798}.
CC -!- PTM: Under hypoxia, hydroxylated by EGLN3.
CC {ECO:0000250|UniProtKB:P14618}.
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:0000250|UniProtKB:P14618}.
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. Deacetylation at Lys-433
CC by SIRT6 promotes its nuclear export into the cytoplasm, leading to
CC suppress its nuclear localization and oncogenic function.
CC {ECO:0000250|UniProtKB:P14618}.
CC -!- PTM: FGFR1-dependent tyrosine phosphorylation is reduced by interaction
CC with TRIM35. {ECO:0000250|UniProtKB:P14618}.
CC -!- DISRUPTION PHENOTYPE: Myeloid-cell-specific ARNTL/BMAL1 and PKM2 double
CC knockout reduces the risk of sepsis lethality which is associated with
CC reduced serum lactate levels and reduced CD274 expression in
CC macrophages. {ECO:0000269|PubMed:29996098}.
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 {ECO:0000250|UniProtKB:P14618}.
CC -!- SIMILARITY: Belongs to the pyruvate kinase family. {ECO:0000305}.
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DR EMBL; D38379; BAA07457.1; -; mRNA.
DR EMBL; X97047; CAA65761.1; -; mRNA.
DR EMBL; AK002341; BAB22025.1; -; mRNA.
DR EMBL; AK135397; BAE22519.1; -; mRNA.
DR EMBL; AK151724; BAE30642.1; -; mRNA.
DR EMBL; AK153483; BAE32031.1; -; mRNA.
DR EMBL; AK155110; BAE33055.1; -; mRNA.
DR EMBL; AK155655; BAE33370.1; -; mRNA.
DR EMBL; AK170892; BAE42098.1; -; mRNA.
DR EMBL; AK168943; BAE40751.1; -; mRNA.
DR EMBL; AK171023; BAE42192.1; -; mRNA.
DR EMBL; AK171033; BAE42199.1; -; mRNA.
DR EMBL; AC160637; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016619; AAH16619.1; -; mRNA.
DR EMBL; BC094663; AAH94663.1; -; mRNA.
DR CCDS; CCDS40659.1; -. [P52480-1]
DR CCDS; CCDS57681.1; -. [P52480-2]
DR PIR; S55921; S55921.
DR RefSeq; NP_001240812.1; NM_001253883.1. [P52480-2]
DR RefSeq; NP_035229.2; NM_011099.3. [P52480-1]
DR RefSeq; XP_006510918.1; XM_006510855.1. [P52480-1]
DR RefSeq; XP_011240975.1; XM_011242673.1.
DR AlphaFoldDB; P52480; -.
DR SMR; P52480; -.
DR BioGRID; 202191; 59.
DR ComplexPortal; CPX-3059; PKM2 pyruvate kinase complex (tetramer). [P52480-1]
DR ComplexPortal; CPX-3060; PKM2 pyruvate kinase complex (dimer). [P52480-1]
DR ComplexPortal; CPX-3096; PKM1 pyruvate kinase complex. [P52480-2]
DR DIP; DIP-40536N; -.
DR IntAct; P52480; 32.
DR MINT; P52480; -.
DR STRING; 10090.ENSMUSP00000034834; -.
DR iPTMnet; P52480; -.
DR PhosphoSitePlus; P52480; -.
DR SwissPalm; P52480; -.
DR REPRODUCTION-2DPAGE; IPI00407130; -.
DR REPRODUCTION-2DPAGE; P52480; -.
DR SWISS-2DPAGE; P52480; -.
DR CPTAC; non-CPTAC-3588; -.
DR CPTAC; non-CPTAC-3654; -.
DR EPD; P52480; -.
DR jPOST; P52480; -.
DR MaxQB; P52480; -.
DR PaxDb; P52480; -.
DR PeptideAtlas; P52480; -.
DR PRIDE; P52480; -.
DR ProteomicsDB; 263452; -. [P52480-1]
DR ProteomicsDB; 263453; -. [P52480-2]
DR Antibodypedia; 14162; 1257 antibodies from 44 providers.
DR DNASU; 18746; -.
DR Ensembl; ENSMUST00000034834; ENSMUSP00000034834; ENSMUSG00000032294. [P52480-1]
DR Ensembl; ENSMUST00000163694; ENSMUSP00000128770; ENSMUSG00000032294. [P52480-2]
DR GeneID; 18746; -.
DR KEGG; mmu:18746; -.
DR UCSC; uc009pyf.2; mouse. [P52480-1]
DR UCSC; uc009pyh.2; mouse. [P52480-2]
DR CTD; 5315; -.
DR MGI; MGI:97591; Pkm.
DR VEuPathDB; HostDB:ENSMUSG00000032294; -.
DR eggNOG; KOG2323; Eukaryota.
DR GeneTree; ENSGT00390000008859; -.
DR HOGENOM; CLU_015439_0_1_1; -.
DR InParanoid; P52480; -.
DR OMA; QVPIVQK; -.
DR OrthoDB; 933620at2759; -.
DR PhylomeDB; P52480; -.
DR TreeFam; TF300390; -.
DR BRENDA; 2.7.1.40; 3474.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-70171; Glycolysis.
DR SABIO-RK; P52480; -.
DR UniPathway; UPA00109; UER00188.
DR BioGRID-ORCS; 18746; 27 hits in 74 CRISPR screens.
DR ChiTaRS; Pkm; mouse.
DR PRO; PR:P52480; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P52480; protein.
DR Bgee; ENSMUSG00000032294; Expressed in retinal neural layer and 262 other tissues.
DR ExpressionAtlas; P52480; baseline and differential.
DR Genevisible; P52480; MM.
DR GO; GO:0005929; C:cilium; IDA:MGI.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:1902912; C:pyruvate kinase complex; ISO:MGI.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0043531; F:ADP binding; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0035402; F:histone kinase activity (H3-T11 specific); ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0030955; F:potassium ion binding; IEA:InterPro.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0004743; F:pyruvate kinase activity; IDA:MGI.
DR GO; GO:0070324; F:thyroid hormone binding; ISO:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0031100; P:animal organ regeneration; ISO:MGI.
DR GO; GO:0006754; P:ATP biosynthetic process; ISO:MGI.
DR GO; GO:0061621; P:canonical glycolysis; IDA:MGI.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IBA:GO_Central.
DR GO; GO:0006006; P:glucose metabolic process; ISO:MGI.
DR GO; GO:0006096; P:glycolytic process; IDA:MGI.
DR GO; GO:0001889; P:liver development; ISO:MGI.
DR GO; GO:2000767; P:positive regulation of cytoplasmic translation; IDA:UniProtKB.
DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0012501; P:programmed cell death; ISO:MGI.
DR GO; GO:0042866; P:pyruvate biosynthetic process; ISO:MGI.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; ISO:MGI.
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 Acetylation; Allosteric enzyme; Alternative splicing; ATP-binding;
KW Cytoplasm; Direct protein sequencing; Glycolysis; Hydroxylation;
KW Isopeptide bond; Kinase; Magnesium; Metal-binding; Methylation;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Potassium; Pyruvate;
KW Reference proteome; Transferase; Translation regulation; Ubl conjugation.
FT CHAIN 1..531
FT /note="Pyruvate kinase PKM"
FT /id="PRO_0000112089"
FT REGION 307..531
FT /note="Interaction with POU5F1"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT REGION 389..433
FT /note="Intersubunit contact"
FT BINDING 70
FT /ligand="L-serine"
FT /ligand_id="ChEBI:CHEBI:33384"
FT /evidence="ECO:0000250|UniProtKB:P14618"
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:0000250|UniProtKB:P14618"
FT BINDING 75
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT BINDING 77
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT BINDING 106
FT /ligand="L-serine"
FT /ligand_id="ChEBI:CHEBI:33384"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT BINDING 113
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT BINDING 114
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT BINDING 120
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT BINDING 207
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P14618"
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:0000250|UniProtKB:P14618"
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:0000250|UniProtKB:P14618"
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:0000250|UniProtKB:P14618"
FT BINDING 464
FT /ligand="L-serine"
FT /ligand_id="ChEBI:CHEBI:33384"
FT /evidence="ECO:0000250|UniProtKB:P14618"
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:0000250|UniProtKB:P14618"
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:0000250|UniProtKB:P14618"
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:0000250|UniProtKB:P14618"
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:0000250|UniProtKB:P14618"
FT MOD_RES 3
FT /note="N6,N6,N6-trimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT MOD_RES 37
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT MOD_RES 41
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT MOD_RES 62
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 66
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 89
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P14618"
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:18034455"
FT MOD_RES 127
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT MOD_RES 148
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT MOD_RES 166
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 166
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 175
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT MOD_RES 195
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT MOD_RES 266
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT MOD_RES 270
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 305
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT MOD_RES 322
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 322
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 403
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT MOD_RES 408
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT MOD_RES 433
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT MOD_RES 475
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 498
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CROSSLNK 115
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT CROSSLNK 166
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT CROSSLNK 266
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT CROSSLNK 270
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P14618"
FT VAR_SEQ 389..433
FT /note="IYHLQLFEELRRLAPITSDPTEAAAVGAVEASFKCCSGAIIVLTK -> MFH
FT RLLFEELVRASSHSTDLMEAMAMGSVEASYKCLAAALIVLTE (in isoform M1)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_025057"
FT MUTAGEN 367
FT /note="K->M: Abolishes pyruvate kinase activity without
FT affecting interaction with the ribosome."
FT /evidence="ECO:0000269|PubMed:28575669"
FT MUTAGEN 464
FT /note="H->A: Abolishes amino-acid binding without affecting
FT interaction with the translating ribosome."
FT /evidence="ECO:0000269|PubMed:28575669"
FT CONFLICT 8
FT /note="A -> V (in Ref. 2; CAA65761)"
FT /evidence="ECO:0000305"
FT CONFLICT 121
FT /note="T -> A (in Ref. 3; BAE30642/BAE32031)"
FT /evidence="ECO:0000305"
FT CONFLICT 158
FT /note="W -> R (in Ref. 1; BAA07457)"
FT /evidence="ECO:0000305"
FT CONFLICT 166
FT /note="K -> E (in Ref. 3; BAE42098)"
FT /evidence="ECO:0000305"
FT CONFLICT 170
FT /note="V -> L (in Ref. 3; BAE30642/BAE32031)"
FT /evidence="ECO:0000305"
FT CONFLICT 177
FT /note="D -> G (in Ref. 3; BAE42199)"
FT /evidence="ECO:0000305"
FT CONFLICT 230
FT /note="K -> R (in Ref. 3; BAE30642/BAE32031)"
FT /evidence="ECO:0000305"
FT CONFLICT 299
FT /note="I -> T (in Ref. 1; BAA07457)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="A -> S (in Ref. 1; BAA07457)"
FT /evidence="ECO:0000305"
FT CONFLICT 327
FT /note="A -> S (in Ref. 1; BAA07457 and 2; CAA65761)"
FT /evidence="ECO:0000305"
FT CONFLICT 333
FT /note="S -> I (in Ref. 1; BAA07457 and 2; CAA65761)"
FT /evidence="ECO:0000305"
FT CONFLICT 485
FT /note="D -> N (in Ref. 3; BAE33055/BAE42192)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 531 AA; 57845 MW; 34CBBC01BC0C047D CRC64;
MPKPHSEAGT AFIQTQQLHA AMADTFLEHM CRLDIDSAPI TARNTGIICT IGPASRSVEM
LKEMIKSGMN VARLNFSHGT HEYHAETIKN VREATESFAS DPILYRPVAV ALDTKGPEIR
TGLIKGSGTA EVELKKGATL KITLDNAYME KCDENILWLD YKNICKVVEV GSKIYVDDGL
ISLQVKEKGA DFLVTEVENG GSLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV
FASFIRKAAD VHEVRKVLGE KGKNIKIISK IENHEGVRRF DEILEASDGI MVARGDLGIE
IPAEKVFLAQ KMMIGRCNRA GKPVICATQM LESMIKKPRP TRAEGSDVAN AVLDGADCIM
LSGETAKGDY PLEAVRMQHL IAREAEAAIY HLQLFEELRR LAPITSDPTE AAAVGAVEAS
FKCCSGAIIV LTKSGRSAHQ VARYRPRAPI IAVTRNPQTA RQAHLYRGIF PVLCKDAVLN
AWAEDVDLRV NLAMDVGKAR GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P
