HGNC Approved Gene Symbol: USP17L9P
Cytogenetic location: 4p16.1 Genomic coordinates (GRCh38) : 4:9,358,382-9,359,974 (from NCBI)
Repetitive DNA sequences are major components of most eukaryotic genomes. The head-to-tail tandem repetitive sequences, such as microsatellite, minisatellite (variable number of tandem repeats), macrosatellite, and megasatellite DNA, are highly polymorphic, repetitive DNA sequences postulated as making a substantial contribution to genomic instability because of their high mutation rates. The 4.7-kb rs447 megasatellite DNA is a highly polymorphic conserved tandem repetitive sequence (Gondo et al., 1998). By sequence analysis of rs447, followed by zoo blot analysis, Saitoh et al. (2000) identified a conserved open reading frame (ORF) encoding USP17. Northern blot analysis revealed expression of a 2.4-kb transcript in heart, brain, liver, and skeletal muscle. The deduced 530-amino acid protein, which is 48% identical to mouse Dub2, contains conserved cys and his domains thought to form the active site of deubiquitinating enzymes. Western blot analysis showed expression of a 60-kD deubiquitinating enzyme. Antisense RNAs for the USP17 mRNA were also transcribed from the rs447 alleles, consistent with the existence of an antisense-transcript-mediated gene expression control for USP17.
Saitoh et al. (2000) determined by 5-prime and 3-prime RACE and RT-PCR analysis that the ORF on rs447, USP17, is a single-exon gene. Promoter analysis identified an inverted CAAT box but no TATA sequence.
Using high-resolution FISH, Okada et al. (2002) mapped the major rs447 locus, which contains the USP17 gene, to chromosome 4p16.1.
To characterize the hypervariability seen in rs447, Okada et al. (2002) conducted a pedigree analysis of rs447 transmission and identified 44 distinct alleles in 74 unrelated chromosomes containing 20 to 103 copies of the 4.7-kb rs447 unit, which contains USP17. Five of 60 parent-to-offspring transmissions clearly showed changes in copy number, indicating a high frequency of meiotic instability. Evidence for somatic mosaicism was also observed.
Gondo, Y., Okada, T., Matsuyama, N., Saitoh, Y., Yanagisawa, Y., Ikeda, J.-E. Human megasatellite DNA RS447: copy-number polymorphisms and interspecies conservation. Genomics 54: 39-49, 1998. [PubMed: 9806828] [Full Text: https://doi.org/10.1006/geno.1998.5545]
Okada, T., Gondo, Y., Goto, J., Kanazawa, I., Hadano, S., Ikeda, J.-E. Unstable transmission of the RS447 human megasatellite tandem repetitive sequence that contains the USP17 deubiquitinating enzyme gene. Hum. Genet. 110: 302-313, 2002. [PubMed: 11941478] [Full Text: https://doi.org/10.1007/s00439-002-0698-2]
Saitoh, Y., Miyamoto, N., Okada, T., Gondo, Y., Showguchi-Miyata, J., Hadano, S., Ikeda, J.-E. The RS447 human megasatellite tandem repetitive sequence encodes a novel deubiquitinating enzyme with a functional promoter. Genomics 67: 291-300, 2000. [PubMed: 10936051] [Full Text: https://doi.org/10.1006/geno.2000.6261]