Cloning and characterization of a novel gene, SHPRH, encoding a conserved putative protein with SNF2/helicase and PHD-finger domains from the 6q24 region Raman Sood, a, * Izabela Makalowska, b Michal Galdzicki, a Ping Hu, a Erica Eddings, a Christiane M. Robbins, a Tracy Moses, a Jin Namkoong, c Suzie Chen, c and Jeffrey M. Trent a,1 a Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA b Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA c Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ 08854, USA Received 21 November 2002; accepted 8 April 2003 Abstract Here we report the identification of a novel transcript containing SNF2, PHD-finger, RING-finger, helicase, and linker histone domains mapping to the q24 band region of human chromosome 6. These domains are characteristic of several DNA repair proteins, transcription factors, and helicases. We have cloned both human and mouse homologs of this novel gene using interexon PCR and RACE technologies. The human cDNA, termed SHPRH, is 6018 bp and codes for a putative protein of 1683 amino acids. The mouse cDNA, termed Shprh, is 7225 bp and codes for a putative protein of 1616 amino acids. The deduced amino acid sequences of the two proteins share 86% identity. Both genes are expressed ubiquitously, with a transcript size of 7.5 kb. Mapping of this gene to 6q24, a region reported to contain a tumor suppressor locus, prompted us to evaluate SHPRH by mutation analysis in tumor cell lines. We have identified one truncating and three missense mutations, thus suggesting SHPRH as a possible candidate for the tumor suppressor gene. © 2003 Elsevier Science (USA). All rights reserved. Keywords: SHPRH; 6q24; Tumor suppressor; SNF2 domain; PHD-finger domain; RING-finger domain; Linker histone domain; DNA/RNA helicases Several studies have shown that the long arm of human chromosome 6 harbors a tumor suppressor gene involved in melanoma [1], ovarian cancer [2], breast cancer [3], pan- creatic cancer [4], prostate cancer [5], cervical cancer [6], childhood endodermal sinus tumors [7], and hepatocellular carcinoma [8]. Allelic loss or deletions of the chromosomal band region 6q24 – q27 seem to be most prevalent in these cancers [9 –13]. Despite the availability of Human Genome Project resources, including ESTs, full-length cDNA clones, and predicted genes, the identity of the tumor sup- pressor gene(s) from the 6q24 – q27 region affecting so many different types of cancer remains elusive. Here we report the cloning and characterization of a novel gene with domains characteristic of DNA repair proteins and tran- scription factors. This gene, referred to as SHPRH, was identified during our efforts to characterize the region en- compassing the transgene integration site of a mouse model displaying a hereditary melanoma phenotype [14,15]. Here we present data on cloning and characterization of both the murine and the human homologs of this gene, including the complete coding sequence, alternative splice variants, ex- pression pattern in various tissues, and genomic organiza- tion. Analysis of the putative protein for homologies and functional motifs to gain insight into its function shows the  Sequence data from this article have been deposited with the Gen- Bank Data Library under Accession Nos. AY161136, AY162264, AY162265, and AY162266. * Corresponding author: NHGRI, NIH, Building 50, Room 5343, 9000 Rockville Pike, Bethesda, MD 20892, USA. Fax: +1-301-594-0023. E-mail address: rsood@nhgri.nih.gov (R. Sood). 1 Current address: Translational Genomics Research Institute, 400 North Fifth Street, Suite 1600, Phoenix, AZ 85004, USA. R Available online at www.sciencedirect.com Genomics 82 (2003) 153–161 www.elsevier.com/locate/ygeno 0888-7543/03/$ – see front matter © 2003 Elsevier Science (USA). All rights reserved. doi:10.1016/S0888-7543(03)00121-6