Human ULK1, a novel serine/threonine kinase related to UNC-51 kinase of Caenorhabditis elegans:: CDNA cloning, expression, and chromosomal assignment
Human ULK1, a novel serine/threonine kinase related to UNC-51 kinase of Caenorhabditis elegans:: CDNA cloning, expression, and chromosomal assignment
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DOI：
10.1006/geno.1998.5340
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发表时间：
1998-07-01
期刊：
影响因子：
4.4
通讯作者：
Shirasawa, T
中科院分区：
文献类型：
--
作者：
Kuroyanagi, H;Yan, J;Shirasawa, T
unc-51基因从秀丽隐杆线虫轴突延伸和生长异常的突变体中分离，编码一种新的丝氨酸/苏氨酸激酶（K. Ogura, et at, 1994, 8: 2389-2400）。在这里，我们报道了UNC-51（秀丽隐杆线虫）样激酶1的UNC-51人类同源物ULK1的分子克隆和特性。对人ULK1 cDNA的序列分析表明，该开放阅读框由1050个氨基酸组成，分子量为112.6 kDa， pi为8.80。同源性搜索分析显示，ULK1与酿酒酵母UNC-51的总体相似性为41%，与酿酒酵母Apg1p的相似性为29%。ULK1、UNC-51和Apg1p的系统发育分析表明，它们构成了一个新的丝氨酸/苏氨酸激酶亚家族。Southern blot分析表明，ULK1基因在人类基因组中全长30- 40kb，为单拷贝基因。Zoo blot分析表明，ULK1激酶在包括哺乳动物、鸟类、爬行动物、两栖动物和鱼类在内的脊椎动物中是保守的。Northern blot分析显示，ULK1在成人组织如骨骼肌、心脏、胰腺、脑、胎盘、肝脏、肾脏和肺中普遍表达，而UNC-51在秀丽隐杆线虫的神经系统中特异性检测到。FISH和RH图谱均证实了ULK1在人类12q24.3染色体上的区域定位。(C) 1998学术出版社。
The unc-51 gene, isolated from mutants of Caenorhabditis elegans exhibiting abnormal axonal extension and growth, encodes a novel serine/threonine kinase (K. Ogura, et at, 1994, Genes Dev. 8: 2389-2400). Here we report the molecular cloning and characterization of the human homologue of UNC-51, designated ULK1, for UNC-51 (C. elegans)-like kinase 1. Sequence analysis of the human ULK1 cDNA showed that an open reading frame is composed of 1050 amino acids with a calculated MW of 112.6 kDa and a pi of 8.80. Homology search analysis showed that ULK1 has 41% overall similarity to UNC-51 and 29% similarity to Apg1p of Saccharomyces cerevisiae. Phylogenetic analysis of ULK1, UNC-51, and Apg1p suggested that they constitute a novel subfamily of serine/threonine kinases. Southern blot analyses suggested that the ULK1 gene spans 30-40 kb in the human genome as a single-copy gene. Zoo blot analysis indicated that ULK1 kinase is conserved among vertebrates including mammals, birds, reptiles, amphibians, and fish. Northern blot analysis revealed that ULK1 is ubiquitously expressed in adult human tissues such as skeletal muscle, heart, pancreas, brain, placenta, liver, kidney, and lung, whereas UNC-51 is specifically detected in the nervous system of C. elegans. Both FISH and RH mapping confirmed the regional localization of ULK1 to human chromosome 12q24.3. (C) 1998 Academic Press.