Abstract
Theunc-51gene, isolated from mutants ofCaenorhabditis elegansexhibiting abnormal axonal extension and growth, encodes a novel serine/threonine kinase (K. Ogura,et al.,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 pIof 8.80. Homology search analysis showed that ULK1 has 41% overall similarity to UNC-51 and 29% similarity to Apg1p ofSaccharomyces cerevisiae.Phylogenetic analysis of ULK1, UNC-51, and Apglp suggested that they constitute a novel subfamily of serine/threonine kinases. Southern blot analyses suggested that theULK1gene 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 ofC. elegans.Both FISH and RH mapping confirmed the regional localization ofULK1to human chromosome 12q24.3.
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