Cloning of a human cDNA encoding a novel enzyme involved in the elongationof long-chain polyunsaturated fatty acids

The Saccharomyces cerevisiae protein ELO2p is involved in the elongation of saturated and monounsaturated fatty acids. Among several sequences with li mited identity with the S. cerevisiae ELO2 gene, a consensus cDNA sequence was identified from the LifeSeq(R) database of Incyte Pharmaceuticals, Inc. Human liver cDNA was amplified by PCR using oligonucleotides complementary to the 5' and 3' ends of the putative human cDNA sequence. The resulting f ull-length sequence, termed HELO1, consisted of 897 bp, which encoded 299 a mino acids. However, in contrast with the ELO2 gene, expression of this ope n reading frame in S. cerevisiae demonstrated that the encoded protein was involved in the elongation of long-chain polyunsaturated fatty acids, as de termined by the conversion of gamma-linolenic acid (C-18:3,C-n-6) into diho mo-gamma-linolenic acid (C-20:3,C-n-6), arachidonic acid (C-20:4,C-n-6) int o adrenic acid (C-22:4,C-n-6), stearidonic acid (C-18:4,C-n-3) into eicosat etraenoic acid (C-20:4,C-n-3), eicosapentaenoic acid (C-20:5,C-n-3) into om ega 3-docosapentaenoic acid (C-22:5,C-n-3) and alpha-linolenic acid (C-18:3 ,C-n-3) into omega 3-eicosatrienoic acid (C-20:3,C-n-3). The predicted amin o acid sequence of the open reading frame had only 29 % identity with the y east ELO2 sequence, contained a single histidine-rich domain and had six tr ansmembrane-spanning regions, as suggested by hydropathy analysis. The tiss ue expression profile revealed that the HELO1 gene is highly expressed in t he adrenal gland and testis. Furthermore, the HELO1 gene is located on chro mosome 6, best known for encoding the major histocompatibility complex, whi ch is essential to the human immune response.