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小鼠泛酸激酶(Pank1)基因编码两种受不同调控的泛酸激酶同工酶。

The murine pantothenate kinase (Pank1) gene encodes two differentially regulated pantothenate kinase isozymes.

作者信息

Rock Charles O, Karim Mohammad A, Zhang Yong-Mei, Jackowski Suzanne

机构信息

Protein Science Division, Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105-2794, USA.

出版信息

Gene. 2002 May 29;291(1-2):35-43. doi: 10.1016/s0378-1119(02)00564-4.

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.

摘要

泛酸激酶(PanK)是辅酶A(CoA)生物合成中的一种限速酶。小鼠泛酸激酶(Pank1)基因由7个内含子和8个外显子组成,位于19号染色体(19C2 - 3)上。Pank1基因编码两种生化性质不同的PanK1蛋白异构体,即PanK1α和PanK1β。两种蛋白质都具有由外显子2至7编码的相同的363个氨基酸催化结构域。PanK1β转录本从外显子1β开始,翻译为一个十肽的氨基末端加上催化结构域。PanK1α转录本在位于外显子1α的一个交替上游位点起始,该位点与外显子2拼接,不包括外显子1β。外显子1α在PanK1α蛋白的氨基末端编码一个184个氨基酸的调节结构域,该结构域赋予游离CoA和长链酰基辅酶A反馈抑制作用,并增加乙酰辅酶A和丙二酰辅酶A对泛酸激酶酶活性的调节。PanK1α和PanK1β转录本的差异表达会根据游离CoA与乙酰辅酶A的比例改变细胞中产生的CoA量,这反映了组织的代谢状态。

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