KPYM_PONAB
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 03-AUG-2022, entry version 107.
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}.
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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 PRIDE; Q5NVN0; -.
DR GeneID; 100174114; -.
DR KEGG; pon:100174114; -.
DR CTD; 5315; -.
DR eggNOG; KOG2323; Eukaryota.
DR InParanoid; Q5NVN0; -.
DR OrthoDB; 933620at2759; -.
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: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; 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 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
