Alternative titles; symbols
HGNC Approved Gene Symbol: VCY
Cytogenetic location: Yq11.221 Genomic coordinates (GRCh38) : Y:13,985,772-13,986,473 (from NCBI)
Members of the variably charged X/Y (VCX/Y) gene family, such as VCY, are expressed exclusively in male germ cells and are located on the X and Y chromosomes (Lahn and Page, 2000).
Ninety-five percent of the length of the human Y chromosome is composed of the nonrecombining portion, or NRY. To identify genes located in the NRY, Lahn and Page (1997) isolated testis cDNAs that hybridized specifically to Y-chromosomal DNA. The authors identified 7 novel genes, BPY1, BPY2 (400013), CDY (400016), PRY (400019), TTY1, TTY2, and XKRY (400015), that appeared to exist in multiple copies on the Y chromosome and were expressed specifically in testis. Transcripts from the TTY1 (testis transcript on Y, gene 1) and TTY2 genes did not contain a significant open reading frame. Lahn and Page (1997) speculated that the selective advantage conferred by the NRY's retention and amplification of male fertility factors accounts for the multitude of testis-specific gene families there. The predicted BPY1 (basic protein on Y, gene 1) protein contains 125 amino acids and has a calculated pI of 9.4. Southern blot analysis indicated that a BPY1 homolog exists on the X chromosome; however, these authors did not isolate a cDNA corresponding to the X-linked gene.
By screening a human testis cDNA library with a VCY cDNA probe, Lahn and Page (2000) obtained several VCY-homologous sequences. Further analysis revealed 2 identical copies of VCY on the Y chromosome, VCY and VCY1B (400050), and multiple related copies on the X chromosome. VCY and VCY1B contain a 30-bp sequence that encodes a 10-amino acid motif rich in glutamic acid that is predicted to be highly negatively charged. Elsewhere in the 125-amino acid predicted VCY/VCY1B protein, an abundance of arg and lys residues creates a positive charge. Both VCY and VCX proteins resemble chromatin-associated proteins and contain putative N-terminal nuclear localization signals. Database analysis identified related sequences in primates, but not other animals. RT-PCR analysis suggested that VCY and VCX expression is restricted to male germ cells.
By immunohistochemical analysis of human testis, Zou et al. (2003) found that VCY localized to nuclei of germ cells of seminiferous epithelium. Fluorescence-tagged VCX8R (VCX3A; 300533) and VCY colocalized in nucleoli in transfected COS-7 cells.
Lahn and Page (2000) stated that approximately 12 X-Y homologous gene pairs were known to be located in the nonrecombining portions of the human sex chromosomes. These X-Y gene pairs fall into 2 categories. In the first category, both X and Y homologs are ubiquitously expressed. In the second category, the X homolog is ubiquitously expressed, whereas the Y homolog is expressed exclusively in the testis. Lahn and Page (2000) described a family of X-Y genes that cannot be assigned to either category. Designated VCX/Y, this gene family has multiple members on both X and Y, and all appear to be expressed exclusively in male germ cells. Members of the VCX/Y family share a high degree of sequence identity, with the exception that a 30-bp unit is tandemly repeated in X-linked members but is present only once in Y-linked members.
Using yeast 2-hybrid analysis, Zou et al. (2003) found that VCY interacted with acidic ribosomal protein P0 (RPLP0; 180510).
Lahn and Page (2000) determined that the VCY gene contains 2 exons.
By analysis of a panel of partial Y chromosomes, Lahn and Page (1997) mapped the BPY1 gene to region 5G on the long arm of the human Y chromosome.
By analysis of BAC clones, Lahn and Page (2000) determined that the VCY and VCY1B genes are separated by no more than 140 kb on the Y chromosome.
Hartz (2016) mapped the VCY gene to chromosome Yq11.22 based on an alignment of the VCY sequence (GenBank AF000979) with the genomic sequence (GRCh38).
Large inverted palindromic repeats that characterize the Y chromosome undergo high rates of structural variation. Shi et al. (2019) studied 1 such palindrome containing 2 copies of the VCY gene and found that healthy males can have 1 to 4 copies of VCY due to such complex structural variation.
Hartz, P. A. Personal Communication. Baltimore, Md. 8/25/2016.
Lahn, B. T., Page, D. C. Functional coherence of the human Y chromosome. Science 278: 675-680, 1997. [PubMed: 9381176] [Full Text: https://doi.org/10.1126/science.278.5338.675]
Lahn, B. T., Page, D. C. A human sex-chromosomal gene family expressed in male germ cells and encoding variably charged proteins. Hum. Molec. Genet. 9: 311-319, 2000. [PubMed: 10607842] [Full Text: https://doi.org/10.1093/hmg/9.2.311]
Shi, W., Massaia, A., Louzada, S., Handsaker, J., Chow, W., McCarthy, S., Collins, J., Hallast, P., Howe, K., Church, D. M., Yang, F., Xue, Y., Tyler-Smith, C. Birth, expansion, and death of VCY-containing palindromes on the human Y chromosome. Genome Biol. 20: 207, 2019. [PubMed: 31610793] [Full Text: https://doi.org/10.1186/s13059-019-1816-y]
Zou, S. W., Zhang, J. C., Zhang, X. D., Miao, S. Y., Zong, S. D., Sheng, Q., Wang, L. F. Expression and localization of VCX/Y proteins and their possible involvement in regulation of ribosome assembly during spermatogenesis. Cell Res. 13: 171-177, 2003. [PubMed: 12862317] [Full Text: https://doi.org/10.1038/sj.cr.7290161]