ID   KPYM_PONAB              Reviewed;         531 AA.
AC   Q5NVN0; Q5R500;
DT   24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   13-SEP-2023, entry version 112.
DE   RecName: Full=Pyruvate kinase PKM;
DE            EC=2.7.1.40 {ECO:0000250|UniProtKB:P14618};
DE   AltName: Full=Pyruvate kinase muscle isozyme;
GN   Name=PKM; Synonyms=PKM2;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain cortex;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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   -!- CATALYTIC ACTIVITY:
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   -!- 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: Has high pyruvate kinase activity by itself and
CC       does not require allosteric activation by D-fructose 1,6-bisphosphate
CC       (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   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P14618}.
CC   -!- PTM: ISGylated. {ECO:0000250|UniProtKB:P14618}.
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: FGFR1-dependent tyrosine phosphorylation is reduced by interaction
CC       with TRIM35. {ECO:0000250|UniProtKB:P14618}.
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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; CR861086; CAH93166.1; -; mRNA.
DR   EMBL; CR925988; CAI29633.1; -; mRNA.
DR   RefSeq; NP_001127083.1; NM_001133611.1.
DR   AlphaFoldDB; Q5NVN0; -.
DR   SMR; Q5NVN0; -.
DR   STRING; 9601.ENSPPYP00000007498; -.
DR   GeneID; 100174114; -.
DR   KEGG; pon:100174114; -.
DR   CTD; 5315; -.
DR   eggNOG; KOG2323; Eukaryota.
DR   InParanoid; Q5NVN0; -.
DR   OrthoDB; 312683at2759; -.
DR   UniPathway; UPA00109; UER00188.
DR   Proteomes; UP000001595; Unplaced.
DR   GO; GO:0005791; C:rough endoplasmic reticulum; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR   GO; GO:0003729; F:mRNA binding; ISS:UniProtKB.
DR   GO; GO:0030955; F:potassium ion binding; IEA:InterPro.
DR   GO; GO:0004743; F:pyruvate kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:2000767; P:positive regulation of cytoplasmic translation; ISS:UniProtKB.
DR   GO; GO:1903672; P:positive regulation of sprouting angiogenesis; ISS:UniProtKB.
DR   CDD; cd00288; Pyruvate_Kinase; 1.
DR   Gene3D; 3.20.20.60; Phosphoenolpyruvate-binding domains; 1.
DR   Gene3D; 2.40.33.10; PK beta-barrel domain-like; 1.
DR   Gene3D; 3.40.1380.20; Pyruvate kinase, C-terminal domain; 2.
DR   InterPro; IPR001697; Pyr_Knase.
DR   InterPro; IPR015813; Pyrv/PenolPyrv_Kinase-like_dom.
DR   InterPro; IPR040442; Pyrv_Kinase-like_dom_sf.
DR   InterPro; IPR011037; Pyrv_Knase-like_insert_dom_sf.
DR   InterPro; IPR018209; Pyrv_Knase_AS.
DR   InterPro; IPR015793; Pyrv_Knase_brl.
DR   InterPro; IPR015795; Pyrv_Knase_C.
DR   InterPro; IPR036918; Pyrv_Knase_C_sf.
DR   InterPro; IPR015806; Pyrv_Knase_insert_dom_sf.
DR   NCBIfam; TIGR01064; pyruv_kin; 1.
DR   PANTHER; PTHR11817; PYRUVATE KINASE; 1.
DR   PANTHER; PTHR11817:SF101; PYRUVATE KINASE PKM; 1.
DR   Pfam; PF00224; PK; 1.
DR   Pfam; PF02887; PK_C; 1.
DR   PRINTS; PR01050; PYRUVTKNASE.
DR   SUPFAM; SSF51621; Phosphoenolpyruvate/pyruvate domain; 1.
DR   SUPFAM; SSF50800; PK beta-barrel domain-like; 1.
DR   SUPFAM; SSF52935; PK C-terminal domain-like; 1.
DR   PROSITE; PS00110; PYRUVATE_KINASE; 1.
PE   2: Evidence at transcript level;
KW   Acetylation; Allosteric enzyme; ATP-binding; Cytoplasm; Glycolysis;
KW   Isopeptide bond; Kinase; Magnesium; Metal-binding; Methylation;
KW   Nucleotide-binding; Phosphoprotein; Potassium; Pyruvate;
KW   Reference proteome; Transferase; Translation regulation; Ubl conjugation.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P11979"
FT   CHAIN           2..531
FT                   /note="Pyruvate kinase PKM"
FT                   /id="PRO_0000112090"
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   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000250|UniProtKB:P11979"
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:0000250|UniProtKB:P14618"
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: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:0000250|UniProtKB:P14618"
FT   MOD_RES         127
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P14618"
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:0000250|UniProtKB:P14618"
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: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:0000250|UniProtKB:P52480"
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:0000250|UniProtKB:P52480"
FT   MOD_RES         322
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P52480"
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: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   CONFLICT        153
FT                   /note="D -> G (in Ref. 1; CAH93166)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        329
FT                   /note="Q -> R (in Ref. 1; CAH93166)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        347
FT                   /note="G -> D (in Ref. 1; CAH93166)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   531 AA;  58018 MW;  86BDD4AEF68B5510 CRC64;
     MSKPHSEAGT AFIQTQQLHA AMADTFLEHM CRLDIDSPPI TARNTGIICT IGPASRSVET
     LKEMIKSGMN VARLNFSHGT HEYHAETIKN VRTATESFAS DPILYRPVAV ALDTKGPEIR
     TGLIKGSGTA EVELKKGATL KITLDNAYME KCDENILWLD YKNICKVVEV GSKIYVDDGL
     ISLQVKQKGA DFLLTEVENG GSLGSKKGVN LPGAAVDLPA VSEKDIQDLK FGVEQDVDMV
     FASFIRKASD VHEVRKVLGE KGKNIKIISK IENHEGVRRF DEILEASDGI MVARGDLGIE
     IPAEKVFLAQ KMMIGRCNRA GKPVICATQM LESMIKKPRP TRAEGSGVAN AVLDGADCIM
     LSGETAKGDY PLEAVRMQHL IAREAEAAMF HRKLFEELVR ASSHSTDLME AMAMGSVEAS
     YKCLAAALIV LTESGRSAHQ VARYRPRAPI IAVTRNPQTA RQAHLYRGIF PVLCKDPVQE
     AWAEDVDLRV NFAMNVGKAR GFFKKGDVVI VLTGWRPGSG FTNTMRVVPV P
//