Pyruvate kinase PKLR

NamePyruvate kinase PKLR
Synonyms
  • 2.7.1.40
  • PK1
  • PKL
  • Pyruvate kinase 1
  • Pyruvate kinase isozymes L/R
  • R-type/L-type pyruvate kinase
  • Red cell/liver pyruvate kinase
Gene NamePKLR
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000092|Pyruvate kinase PKLR
MSIQENISSLQLRSWVSKSQRDLAKSILIGAPGGPAGYLRRASVAQLTQELGTAFFQQQQ
LPAAMADTFLEHLCLLDIDSEPVAARSTSIIATIGPASRSVERLKEMIKAGMNIARLNFS
HGSHEYHAESIANVREAVESFAGSPLSYRPVAIALDTKGPEIRTGILQGGPESEVELVKG
SQVLVTVDPAFRTRGNANTVWVDYPNIVRVVPVGGRIYIDDGLISLVVQKIGPEGLVTQV
ENGGVLGSRKGVNLPGAQVDLPGLSEQDVRDLRFGVEHGVDIVFASFVRKASDVAAVRAA
LGPEGHGIKIISKIENHEGVKRFDEILEVSDGIMVARGDLGIEIPAEKVFLAQKMMIGRC
NLAGKPVVCATQMLESMITKPRPTRAETSDVANAVLDGADCIMLSGETAKGNFPVEAVKM
QHAIAREAEAAVYHRQLFEELRRAAPLSRDPTEVTAIGAVEAAFKCCAAAIIVLTTTGRS
AQLLSRYRPRAAVIAVTRSAQAARQVHLCRGVFPLLYREPPEAIWADDVDRRVQFGIESG
KLRGFLRVGDLVIVVTGWRPGSGYTNIMRVLSIS
Number of residues574
Molecular Weight61829.575
Theoretical pI7.83
GO Classification
Functions
  • ATP binding
  • potassium ion binding
  • kinase activity
  • pyruvate kinase activity
  • magnesium ion binding
Processes
  • response to hypoxia
  • energy reserve metabolic process
  • cellular response to insulin stimulus
  • ATP biosynthetic process
  • response to nutrient
  • pyruvate biosynthetic process
  • canonical glycolysis
  • endocrine pancreas development
  • positive regulation of cellular metabolic process
  • response to ATP
  • small molecule metabolic process
  • response to glucose
  • response to heat
  • response to lithium ion
  • carbohydrate metabolic process
  • response to other organism
  • glucose metabolic process
  • response to cAMP
Components
  • cytosol
  • extracellular exosome
General FunctionPyruvate kinase activity
Specific FunctionPlays a key role in glycolysis.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID3327365
UniProtKB IDP30613
UniProtKB Entry NameKPYR_HUMAN
Cellular LocationNot Available
Gene sequence
>lcl|BSEQ0010140|Pyruvate kinase PKLR (PKLR)
ATGTCGATCCAGGAGAACATATCATCCCTGCAGCTTCGGTCATGGGTCTCTAAGTCCCAA
AGAGACTTAGCAAAGTCCATCCTGATTGGGGCTCCAGGAGGGCCAGCGGGGTATCTGCGG
CGGGCCAGTGTGGCCCAACTGACCCAGGAGCTGGGCACTGCCTTCTTCCAGCAGCAGCAG
CTGCCAGCTGCTATGGCAGACACCTTCCTGGAACACCTCTGCCTACTGGACATTGACTCC
GAGCCCGTGGCTGCTCGCAGTACCAGCATCATTGCCACCATCGGGCCAGCATCTCGCTCC
GTGGAGCGCCTCAAGGAGATGATCAAGGCCGGGATGAACATTGCGCGACTCAACTTCTCC
CACGGCTCCCACGAGTACCATGCTGAGTCCATCGCCAACGTCCGGGAGGCGGTGGAGAGC
TTTGCAGGTTCCCCACTCAGCTACCGGCCCGTGGCCATCGCCCTGGACACCAAGGGACCG
GAGATCCGCACTGGGATCCTGCAGGGGGGTCCAGAGTCGGAAGTGGAGCTGGTGAAGGGC
TCCCAGGTGCTGGTGACTGTGGACCCCGCGTTCCGGACGCGGGGGAACGCGAACACCGTG
TGGGTGGACTACCCCAATATTGTCCGGGTCGTGCCGGTGGGGGGCCGCATCTACATTGAC
GACGGGCTCATCTCCCTAGTGGTCCAGAAAATCGGCCCAGAGGGACTGGTGACCCAAGTG
GAGAACGGCGGCGTCCTGGGCAGCCGGAAGGGCGTGAACTTGCCAGGGGCCCAGGTGGAC
TTGCCCGGGCTGTCCGAGCAGGACGTCCGAGACCTGCGCTTCGGGGTGGAGCATGGGGTG
GACATCGTCTTTGCCTCCTTTGTGCGGAAAGCCAGCGACGTGGCTGCCGTCAGGGCTGCT
CTGGGTCCGGAAGGACACGGCATCAAGATCATCAGCAAAATTGAGAACCACGAAGGCGTG
AAGAGGTTTGATGAAATCCTGGAGGTGAGCGACGGCATCATGGTGGCACGGGGGGACCTA
GGCATCGAGATCCCAGCAGAGAAGGTTTTCCTGGCTCAGAAGATGATGATTGGGCGCTGC
AACTTGGCGGGCAAGCCTGTTGTCTGTGCCACACAGATGCTGGAGAGCATGATTACCAAG
CCCCGGCCAACGAGGGCAGAGACAAGCGATGTCGCCAATGCTGTGCTGGATGGGGCTGAC
TGCATCATGCTGTCAGGGGAGACTGCCAAGGGCAACTTCCCTGTGGAAGCGGTGAAGATG
CAGCATGCGATTGCCCGGGAGGCAGAGGCCGCAGTGTACCACCGGCAGCTGTTTGAGGAG
CTACGTCGGGCAGCGCCACTAAGCCGTGATCCCACTGAGGTCACCGCCATTGGTGCTGTG
GAGGCTGCCTTCAAGTGCTGTGCTGCTGCCATCATTGTGCTGACCACAACTGGCCGCTCA
GCCCAGCTTCTGTCTCGGTACCGACCTCGGGCAGCAGTCATTGCTGTCACCCGCTCTGCC
CAGGCTGCCCGCCAGGTCCACTTATGCCGAGGAGTCTTCCCCTTGCTTTACCGTGAACCT
CCAGAAGCCATCTGGGCAGATGATGTAGATCGCCGGGTGCAATTTGGCATTGAAAGTGGA
AAGCTCCGTGGCTTCCTCCGTGTTGGAGACCTGGTGATTGTGGTGACAGGCTGGCGACCT
GGCTCCGGCTACACCAACATCATGCGGGTGCTAAGCATATCCTGA
GenBank Gene IDAB015983
GeneCard IDNot Available
GenAtlas IDPKLR
HGNC IDHGNC:9020
Chromosome Location1
Locus1q21
References
  1. Kanno H, Fujii H, Hirono A, Miwa S: cDNA cloning of human R-type pyruvate kinase and identification of a single amino acid substitution (Thr384----Met) affecting enzymatic stability in a pyruvate kinase variant (PK Tokyo) associated with hereditary hemolytic anemia. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8218-21. 1896471
  2. Tani K, Fujii H, Nagata S, Miwa S: Human liver type pyruvate kinase: complete amino acid sequence and the expression in mammalian cells. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1792-5. 3126495
  3. Kanno H, Fujii H, Miwa S: Structural analysis of human pyruvate kinase L-gene and identification of the promoter activity in erythroid cells. Biochem Biophys Res Commun. 1992 Oct 30;188(2):516-23. 1445295
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  5. Tani K, Fujii H, Tsutsumi H, Sukegawa J, Toyoshima K, Yoshida MC, Noguchi T, Tanaka T, Miwa S: Human liver type pyruvate kinase: cDNA cloning and chromosomal assignment. Biochem Biophys Res Commun. 1987 Mar 13;143(2):431-8. 3566732
  6. Kanno H, Fujii H, Tsujino G, Miwa S: Molecular basis of impaired pyruvate kinase isozyme conversion in erythroid cells: a single amino acid substitution near the active site and decreased mRNA content of the R-type PK. Biochem Biophys Res Commun. 1993 Apr 15;192(1):46-52. 8476433
  7. Beutler E, Baronciani L: Mutations in pyruvate kinase. Hum Mutat. 1996;7(1):1-6. 8664896
  8. Baronciani L, Bianchi P, Zanella A: Hematologically important mutations: red cell pyruvate kinase. Blood Cells Mol Dis. 1996;22(1):85-9. 8807089
  9. Baronciani L, Bianchi P, Zanella A: Hematologically important mutations: red cell pyruvate kinase (1st update). Blood Cells Mol Dis. 1996;22(3):259-64. 9075576
  10. Baronciani L, Bianchi P, Zanella A: Hematologically important mutations: red cell pyruvate kinase (2nd update). Blood Cells Mol Dis. 1998 Sep;24(3):273-9. 10087985
  11. Bianchi P, Zanella A: Hematologically important mutations: red cell pyruvate kinase (Third update). Blood Cells Mol Dis. 2000 Feb;26(1):47-53. 10772876
  12. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  13. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  14. Valentini G, Chiarelli LR, Fortin R, Dolzan M, Galizzi A, Abraham DJ, Wang C, Bianchi P, Zanella A, Mattevi A: Structure and function of human erythrocyte pyruvate kinase. Molecular basis of nonspherocytic hemolytic anemia. J Biol Chem. 2002 Jun 28;277(26):23807-14. Epub 2002 Apr 17. 11960989
  15. Neubauer B, Lakomek M, Winkler H, Parke M, Hofferbert S, Schroter W: Point mutations in the L-type pyruvate kinase gene of two children with hemolytic anemia caused by pyruvate kinase deficiency. Blood. 1991 May 1;77(9):1871-5. 2018831
  16. Kanno H, Fujii H, Hirono A, Omine M, Miwa S: Identical point mutations of the R-type pyruvate kinase (PK) cDNA found in unrelated PK variants associated with hereditary hemolytic anemia. Blood. 1992 Mar 1;79(5):1347-50. 1536957
  17. Kanno H, Fujii H, Miwa S: Low substrate affinity of pyruvate kinase variant (PK Sapporo) caused by a single amino acid substitution (426 Arg-->Gln) associated with hereditary hemolytic anemia. Blood. 1993 May 1;81(9):2439-41. 8481523
  18. Baronciani L, Beutler E: Analysis of pyruvate kinase-deficiency mutations that produce nonspherocytic hemolytic anemia. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4324-7. 8483951
  19. Kanno H, Ballas SK, Miwa S, Fujii H, Bowman HS: Molecular abnormality of erythrocyte pyruvate kinase deficiency in the Amish. Blood. 1994 Apr 15;83(8):2311-6. 8161798
  20. Lenzner C, Nurnberg P, Thiele BJ, Reis A, Brabec V, Sakalova A, Jacobasch G: Mutations in the pyruvate kinase L gene in patients with hereditary hemolytic anemia. Blood. 1994 May 15;83(10):2817-22. 8180378
  21. Baronciani L, Beutler E: Molecular study of pyruvate kinase deficient patients with hereditary nonspherocytic hemolytic anemia. J Clin Invest. 1995 Apr;95(4):1702-9. 7706479
  22. Beutler E, Westwood B, van Zwieten R, Roos D: G-->T transition at cDNA nt 110 (K37Q) in the PKLR (pyruvate kinase) gene is the molecular basis of a case of hereditary increase of red blood cell ATP. Hum Mutat. 1997;9(3):282-5. 9090535
  23. Zarza R, Alvarez R, Pujades A, Nomdedeu B, Carrera A, Estella J, Remacha A, Sanchez JM, Morey M, Cortes T, Perez Lungmus G, Bureo E, Vives Corrons JL: Molecular characterization of the PK-LR gene in pyruvate kinase deficient Spanish patients. Red Cell Pathology Group of the Spanish Society of Haematology (AEHH). Br J Haematol. 1998 Nov;103(2):377-82. 9827908
  24. Cohen-Solal M, Prehu C, Wajcman H, Poyart C, Bardakdjian-Michau J, Kister J, Prome D, Valentin C, Bachir D, Galacteros F: A new sickle cell disease phenotype associating Hb S trait, severe pyruvate kinase deficiency (PK Conakry), and an alpha2 globin gene variant (Hb Conakry). Br J Haematol. 1998 Dec;103(4):950-6. 9886305
  25. Pastore L, Della Morte R, Frisso G, Alfinito F, Vitale D, Calise RM, Ferraro F, Zagari A, Rotoli B, Salvatore F: Novel mutations and structural implications in R-type pyruvate kinase-deficient patients from Southern Italy. Hum Mutat. 1998;11(2):127-34. 9482576
  26. Zanella A, Bianchi P, Fermo E, Iurlo A, Zappa M, Vercellati C, Boschetti C, Baronciani L, Cotton F: Molecular characterization of the PK-LR gene in sixteen pyruvate kinase-deficient patients. Br J Haematol. 2001 Apr;113(1):43-8. 11328279
  27. van Wijk R, Huizinga EG, van Wesel AC, van Oirschot BA, Hadders MA, van Solinge WW: Fifteen novel mutations in PKLR associated with pyruvate kinase (PK) deficiency: structural implications of amino acid substitutions in PK. Hum Mutat. 2009 Mar;30(3):446-53. doi: 10.1002/humu.20915. 19085939
  28. Lyon GJ, Jiang T, Van Wijk R, Wang W, Bodily PM, Xing J, Tian L, Robison RJ, Clement M, Lin Y, Zhang P, Liu Y, Moore B, Glessner JT, Elia J, Reimherr F, van Solinge WW, Yandell M, Hakonarson H, Wang J, Johnson WE, Wei Z, Wang K: Exome sequencing and unrelated findings in the context of complex disease research: ethical and clinical implications. Discov Med. 2011 Jul;12(62):41-55. 21794208