Identification and characterization of a novel human DEXH motif containing gene : Helicase LIke protein (HLP)

Abstract

A novel human gene is cloned by using a monoclonal antibody, 17 0A1, which recognizes a nucleolar peptide of molecular weight 90 kDa. The gene is ubiquitously expressed in various cell lines tested so far. The composite nucleotide sequence consists of 3,910 nucleotides. It contains a single open reading frame encoding a polypeptide of 1,245 amino acids with a calculated molecular weight of 137 kDa. The deduced amino acid sequence shows seven well conserved helicase domains. It belongs to the member of the DEXH protein family which is composed of DNA and RNA helicases; thus, it is named as Helicase Like Protein ( HLP). The HLP gene contains a leucine zipper motif between helicase domains Ia and II, and a putative nucleolar localization sequence. Homology search of HLP shows two highly significant matches at the amino acid sequence level: yeast SKI2 gene (GenBank L13469) and a partial human ORF2 from human male myeloblast KB-1 cell line (GenBank D29641). The SKI2 gene of Saccharomyces cerevisiae is known to be involved in antiviral activities through inhibition of translation of cap or poly (A) deficient mRNAs. Pairwise alignments of HLP and SKI2, or human ORF2 show overall 38% sequence identities and 65% sequence similarities when conservative amino acid changes are included. By sequencing analysis of the HLP genomic clone, the gene has been localized to the 11 kb intergenic space between RD and RP1 in the MHC class III region on chromosome 6p21. The RD gene is present in head-to-head configuration 65 bp away from the first methionine codon of the HLP gene. RP1 is present 351 bp downstream of the stop codon in head-to-tail configuration.