Alternative titles; symbols
HGNC Approved Gene Symbol: HHLA1
Cytogenetic location: 8q24.22 Genomic coordinates (GRCh38) : 8:132,061,480-132,111,157 (from NCBI)
Human endogenous retroviruses (HERVs) are repetitive elements, derived from ancient germline retroviral infections, that have increased in copy number by further rounds of infection, retrotransposition, and/or duplication. The HERV-H family has been shown to play a role in the expression of a variety of adjacent genes. For example, Feuchter-Murthy et al. (1993) isolated a teratocarcinoma cell line transcript, PLA2L (phospholipase A2-like), which initiates in the long terminal repeat (LTR) of an HERV-H element present in an intron and splices into downstream exons. They found that the teratocarcinoma cells contained additional, alternatively spliced PLA2L mRNAs, designated AF6 through -8, which lack the coding regions for the phospholipase A2 (PLA2)-like domains. Kowalski et al. (1999) determined that PLA2L is a tripartite fusion transcript expressed from the HERV-H element's promoter and containing exons from a novel gene, HHLA1, and from OC90 (601658), a gene encoding an inner ear protein with PLA2 domains. The coding regions of the AF6, -7, and -8 mRNAs are derived only from the HHLA1 gene and encode a predicted 305-amino acid protein. The authors hypothesized that the human HHLA1 and OC90 genes are normally expressed independently from different promoters, and that the intergenic splicing event that generates PLA2L is specific to teratocarcinoma cells. The HERV-H element is located within an intron of HHLA1 and the OC90 gene is located less than 10 kb downstream of HHLA1.
Kowalski et al. (1997) determined that the HERV-H element at this locus integrated 15 to 20 million years ago since it is present in chimpanzee and gorilla but absent in orangutan and lower primates. They mapped the HHLA1 locus to 8q24.
Feuchter-Murthy, A. E., Freeman, J. D., Mager, D. L. Splicing of a human endogenous retrovirus to a novel phospholipase A2 related gene. Nucleic Acids Res. 21: 135-143, 1993. [PubMed: 8382789] [Full Text: https://doi.org/10.1093/nar/21.1.135]
Kowalski, P. E., Freeman, J. D., Mager, D. L. Intergenic splicing between a HERV-H endogenous retrovirus and two adjacent human genes. Genomics 57: 371-379, 1999. [PubMed: 10329003] [Full Text: https://doi.org/10.1006/geno.1999.5787]
Kowalski, P. E., Freeman, J. D., Nelson, D. T., Mager, D. L. Genomic structure and evolution of a novel gene (PLA2L) with duplicated phospholipase A2-like domains. Genomics 39: 38-46, 1997. [PubMed: 9027484] [Full Text: https://doi.org/10.1006/geno.1996.4471]