Prkag1基因编码哺乳动物AMP-activated protein kinase (AMPK)的γ1亚基,AMPK是一种异源三聚体蛋白激酶,由α、β和γ亚基组成。α亚基是催化亚基,β和γ亚基是非催化亚基,它们与α亚基共同构成活性激酶复合物。Prkag1在哺乳动物中具有广泛的表达,其基因在啮齿类动物、大鼠和人类中高度保守,蛋白水平上同源性高达96%[1]。Prkag1基因含有12个外显子,具有短的插入序列,在染色体15的远端区域定位[1]。Prkag1的突变与结肠癌的发生有关[2]。Prkag1的表达与年龄相关,随着年龄的增长而下降,与多病共存和多维度衰弱风险相关[4]。Prkag1的变异与复杂区域疼痛综合征1型(CRPS-1)的发生相关,男性比女性更易表达这些罕见等位基因[5]。Prkag1基因的SNP与Holstein奶牛的血清酮体和牛奶产量相关[6]。Prkag1的表达和活性在细胞能量代谢和自噬过程中发挥重要作用。PRKDC/DNA-PKcs作为DNA损伤反应的效应分子,通过磷酸化PRKAG1/AMPKγ1,调节AMPK复合物在溶酶体的定位和活性,从而影响自噬和细胞代谢[3]。Prkag1的表达和活性对健康和长寿至关重要,维持其活性可以预防代谢静止并保持健康的衰老过程[4]。
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2. Choi, Mi Ryoung, An, Chang Hyeok, Yoo, Nam Jin, Lee, Sug Hyung. . Frameshift mutations of PRKAG1 gene encoding an AMPK gamma subunit in colorectal cancers. In Journal of gastrointestinal and liver diseases : JGLD, 23, 343-5. doi:. https://pubmed.ncbi.nlm.nih.gov/25267969/
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5. Shaikh, Samiha S, Goebel, Andreas, Lee, Michael C, Menon, David K, Woods, C Geoffrey. 2024. Evidence of a genetic background predisposing to complex regional pain syndrome type 1. In Journal of medical genetics, 61, 163-170. doi:10.1136/jmg-2023-109236. https://pubmed.ncbi.nlm.nih.gov/37816627/
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