title: The murine pantothenate kinase (Pank1) gene encodes two differentially regulated pantothenate kinase isozymes.
abstract: Pantothenate kinase (PanK) is a rate-determining enzyme in coenzyme A (CoA) biosynthesis. The mouse murine pantothenate kinase (Pank1) gene consists of seven introns and eight exons and is located on chromosome 19 (19C2-3). Two biochemically distinct PanK1 protein isoforms, PanK1 alpha and PanK1 beta, are encoded by the Pank1 gene. Both proteins have the same 363 amino acid catalytic domain encoded by exons 2 through 7. The PanK1 beta transcript begins with exon 1 beta and translates into a ten-residue amino terminus plus the catalytic domain. The PanK1 alpha transcript initiates at an alternate upstream site at exon 1 alpha which is spliced with exon 2, excluding exon 1 beta. Exon 1 alpha encodes a 184-residue regulatory domain at the amino terminus of the PanK1 alpha protein that confers feedback inhibition by free CoA and long-chain acyl-CoA, and increases the regulation of PanK enzyme activity by acetyl-CoA and malonyl-CoA. Differential expression of the PanK1 alpha and PanK1 beta transcripts would alter the amount of CoA produced in cells as a function of the ratio of free CoA to acetyl-CoA, a reflection of the metabolic status of the tissue.
authors.affiliation: Protein Science Division, Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105-2794, USA.
authors.forename: Charles O
authors.initials: CO
authors.lastname: Rock
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Karim
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Zhang
authors.forename: Suzanne
authors.initials: S
authors.lastname: Jackowski
mesh_terms: D000105:Acetyl Coenzyme A / Q000494:pharmacology; D017398:Alternative Splicing; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003065:Coenzyme A / Q000494:pharmacology; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005091:Exons; D015971:Gene Expression Regulation, Enzymologic; D005796:Genes / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010171:Palmitoyl Coenzyme A; D000105:Acetyl Coenzyme A; D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase; D003065:Coenzyme A