ID   KPYR_CANLF              Reviewed;         574 AA.
AC   Q29536; F1P923; F1PXP8; F1PY57;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   21-MAR-2012, sequence version 2.
DT   27-MAR-2024, entry version 152.
DE   RecName: Full=Pyruvate kinase PKLR;
DE            EC=2.7.1.40 {ECO:0000250|UniProtKB:P30613};
DE   AltName: Full=Pyruvate kinase isozymes L/R;
GN   Name=PKLR;
OS   Canis lupus familiaris (Dog) (Canis familiaris).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX   NCBI_TaxID=9615;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Boxer;
RX   PubMed=16341006; DOI=10.1038/nature04338;
RA   Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B.,
RA   Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., Mauceli E.,
RA   Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F.,
RA   Smith D.R., deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W.,
RA   Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S.,
RA   Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A.,
RA   Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P.,
RA   Searle S.M.J., Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A.,
RA   Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P.,
RA   Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., Bachantsang P.,
RA   Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B.,
RA   Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A.,
RA   Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M.,
RA   Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S.,
RA   Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L.,
RA   Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S.,
RA   Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C.,
RA   Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G.,
RA   Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N.,
RA   Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A.,
RA   Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A.,
RA   Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M.,
RA   Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L.,
RA   LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A.,
RA   Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S.,
RA   Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T.,
RA   Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A.,
RA   Naylor J., Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N.,
RA   Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., Osman S.,
RA   Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M.,
RA   Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F.,
RA   Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T.,
RA   Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C.,
RA   Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C.,
RA   Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D.,
RA   Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H.,
RA   Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J.,
RA   Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J.,
RA   Zembek L., Zimmer A., Lander E.S.;
RT   "Genome sequence, comparative analysis and haplotype structure of the
RT   domestic dog.";
RL   Nature 438:803-819(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 56-574.
RC   TISSUE=Reticulocyte;
RX   PubMed=7520391;
RA   Whitney K.M., Goodman S.A., Bailey E.M., Lothrop C.D. Jr.;
RT   "The molecular basis of canine pyruvate kinase deficiency.";
RL   Exp. Hematol. 22:866-874(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-134 (ISOFORM L-TYPE).
RC   TISSUE=Liver;
RA   Staten N.R.;
RL   Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Pyruvate kinase that catalyzes the conversion of
CC       phosphoenolpyruvate to pyruvate with the synthesis of ATP, and which
CC       plays a key role in glycolysis. {ECO:0000250|UniProtKB:P30613}.
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:P30613};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18159;
CC         Evidence={ECO:0000250|UniProtKB:P30613};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:P30613};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000250|UniProtKB:P30613};
CC   -!- COFACTOR:
CC       Name=K(+); Xref=ChEBI:CHEBI:29103;
CC         Evidence={ECO:0000250|UniProtKB:P30613};
CC   -!- ACTIVITY REGULATION: Allosterically activated by fructose 1,6-
CC       bisphosphate. {ECO:0000250|UniProtKB:P30613}.
CC   -!- PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-
CC       glyceraldehyde 3-phosphate: step 5/5. {ECO:0000250|UniProtKB:P30613}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P30613}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=R-type; Synonyms=PKR;
CC         IsoId=Q29536-1; Sequence=Displayed;
CC       Name=L-type; Synonyms=PKL;
CC         IsoId=Q29536-2; Sequence=VSP_042444;
CC   -!- DISEASE: Note=Defects in PKLR are a cause of inherited hemolytic
CC       anemia, an autosomal recessive disease of the Basenji dog that closely
CC       resembles human pyruvate kinase deficiency.
CC       {ECO:0000269|PubMed:7520391}.
CC   -!- MISCELLANEOUS: There are 4 isozymes of pyruvate kinase in mammals: L,
CC       R, M1 and M2. 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. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the pyruvate kinase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=DN338485; Type=Miscellaneous discrepancy; Note=Derived from EST data.; Evidence={ECO:0000305};
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DR   EMBL; AAEX03005338; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AH004600; AAB31627.2; -; mRNA.
DR   EMBL; DN338485; -; NOT_ANNOTATED_CDS; mRNA.
DR   RefSeq; NP_001242947.1; NM_001256018.1.
DR   RefSeq; NP_001243191.1; NM_001256262.1. [Q29536-1]
DR   AlphaFoldDB; Q29536; -.
DR   SMR; Q29536; -.
DR   STRING; 9615.ENSCAFP00000061352; -.
DR   PaxDb; 9612-ENSCAFP00000024956; -.
DR   Ensembl; ENSCAFT00000026853.5; ENSCAFP00000024956.4; ENSCAFG00000016959.6. [Q29536-2]
DR   Ensembl; ENSCAFT00000035475.4; ENSCAFP00000030738.4; ENSCAFG00000016959.6. [Q29536-1]
DR   Ensembl; ENSCAFT00030047792.1; ENSCAFP00030041802.1; ENSCAFG00030025851.1. [Q29536-1]
DR   Ensembl; ENSCAFT00030047805.1; ENSCAFP00030041815.1; ENSCAFG00030025851.1. [Q29536-2]
DR   Ensembl; ENSCAFT00040001436.1; ENSCAFP00040001228.1; ENSCAFG00040000772.1. [Q29536-1]
DR   Ensembl; ENSCAFT00040001457.1; ENSCAFP00040001246.1; ENSCAFG00040000772.1. [Q29536-2]
DR   Ensembl; ENSCAFT00805006609; ENSCAFP00805005114; ENSCAFG00805003554. [Q29536-1]
DR   Ensembl; ENSCAFT00845021649.1; ENSCAFP00845017017.1; ENSCAFG00845012059.1. [Q29536-1]
DR   Ensembl; ENSCAFT00845021714.1; ENSCAFP00845017074.1; ENSCAFG00845012059.1. [Q29536-2]
DR   GeneID; 490425; -.
DR   KEGG; cfa:490425; -.
DR   CTD; 5313; -.
DR   VEuPathDB; HostDB:ENSCAFG00845012059; -.
DR   eggNOG; KOG2323; Eukaryota.
DR   GeneTree; ENSGT00390000008859; -.
DR   InParanoid; Q29536; -.
DR   OrthoDB; 312683at2759; -.
DR   Reactome; R-CFA-70171; Glycolysis.
DR   UniPathway; UPA00109; UER00188.
DR   Proteomes; UP000002254; Chromosome 7.
DR   Proteomes; UP000694429; Chromosome 7.
DR   Proteomes; UP000694542; Chromosome 7.
DR   Proteomes; UP000805418; Chromosome 7.
DR   Bgee; ENSCAFG00000016959; Expressed in liver and 31 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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:0030955; F:potassium ion binding; IEA:InterPro.
DR   GO; GO:0004743; F:pyruvate kinase activity; IBA:GO_Central.
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:0016310; P:phosphorylation; IEA:UniProtKB-KW.
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; 1.
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:SF31; PYRUVATE KINASE PKLR; 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   Allosteric enzyme; Alternative splicing; ATP-binding; Glycolysis; Kinase;
KW   Magnesium; Manganese; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW   Potassium; Pyruvate; Reference proteome; Transferase.
FT   CHAIN           1..574
FT                   /note="Pyruvate kinase PKLR"
FT                   /id="PRO_0000112093"
FT   BINDING         116
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   BINDING         118..121
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P14618"
FT   BINDING         118
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   BINDING         120
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   BINDING         156
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   BINDING         157
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   BINDING         163
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P14618"
FT   BINDING         250
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P14618"
FT   BINDING         313
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   BINDING         315
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   BINDING         338
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   BINDING         339
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   BINDING         339
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   BINDING         371
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   BINDING         475..480
FT                   /ligand="beta-D-fructose 1,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:32966"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   BINDING         525
FT                   /ligand="beta-D-fructose 1,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:32966"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   BINDING         532
FT                   /ligand="beta-D-fructose 1,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:32966"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   BINDING         559..564
FT                   /ligand="beta-D-fructose 1,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:32966"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   SITE            313
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250|UniProtKB:P00549"
FT   MOD_RES         2
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   MOD_RES         19
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   MOD_RES         26
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   MOD_RES         43
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   MOD_RES         292
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P30613"
FT   VAR_SEQ         1..33
FT                   /note="MSSQENIQPQELWSRISKSQRDLAKSILIGAPG -> ME (in isoform
FT                   L-type)"
FT                   /evidence="ECO:0000303|Ref.3"
FT                   /id="VSP_042444"
FT   CONFLICT        423
FT                   /note="A -> R (in Ref. 2; AAB31627)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        458..459
FT                   /note="GA -> AT (in Ref. 2; AAB31627)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   574 AA;  62048 MW;  F18E28450B1C7F30 CRC64;
     MSSQENIQPQ ELWSRISKSQ RDLAKSILIG APGGPAGYLR RASVAQLTLE LGTAFFQQQQ
     LSAAMADTFL EHLCLLDIDS EPVAARSTSI IATIGPASHS VERLKEMIKA GMNIARLNFS
     HGSHEYHAQS IANIREAVES FATSPLGYRP VAIALDTKGP EIRTGVLKGG PETEVELVKG
     SWVLVTVDPA FRTLGDAHTV WVDYPNIVKV VPVGGRIFID DGLISLQVKK IDRKGLETQV
     ENGGLLGSRK GVNLPGAEVD LPGLSEQDAQ DLRFGVEHNV DIVFASFVRK ASDVAAIRAA
     LGPEGRTIKI ISKIENHEGV KKFDEILEVS DGIMVARGDL GIEIPAEKVF LAQKMMIGRC
     NLAGKPVVCA TQMLESMITK PRPTRAETSD VANAVLDGAD CIMLSGETAK GKFPVEAVKM
     QHAIAREAEA AVYHRQLFEE LRRAAPLSRD PTEVTAIGAV EAAFKCCAAA IIVLTKTGRS
     AQLLSRYRPR AAVIAVTRSA QAARQAHLCR GVFPLLYSEP PEAIWADDVD RRVQFGIESG
     KLRGFLRVGD LVIVVTGWRP GSGYTNIMRV LSIS
//