Alternative titles; symbols
HGNC Approved Gene Symbol: SERPINA2
Cytogenetic location: 14q32.1 Genomic coordinates (GRCh38): 14:89,300,001-95,800,000
SERPINA2P is part of a cluster of structurally related serine protease inhibitor (SERPIN) genes on chromosome 14. However, SERPINA2P appears to be a pseudogene (Rollini and Fournier, 1997).
Kelsey et al. (1988) identified, 10 kb downstream of the authentic alpha-1-antitrypsin gene (AAT or PI; 107400), a genomic sequence with considerable homology to the AAT gene. They designated this sequence the alpha-1-antitrypsin-related gene (ATR). They introduced the AAT and ATR genes separately into L-cells by transfection in order to establish a method for distinguishing between expression of the 2 genes. RNA probes from the cloned ATR region were then used in a ribonuclease protection assay against RNA from a range of human adult and fetal tissues. No evidence of expression of ATR was found, indicating that this gene is probably a pseudogene.
Bao et al. (1988) cloned a 7.7-kb EcoRI genomic DNA fragment highly homologous to the human AAT gene. The nucleotide sequence of the ATR gene showed extensive homology with the authentic AAT gene in the introns as well as exons. The conservation of all RNA splice sites and lack of internal termination codons in the exons suggested that it may not be a classic pseudogene. If expressed, it would result in a protein of 420 amino acid residues, exhibiting a 70% overall homology with AAT. The signal peptide sequence was well conserved, but the active site of protease inhibition (met-ser) in AAT had been changed to trp-ser. The findings suggested that the putative protein is a secretory serine protease inhibitor with an altered substrate specificity. Since even the introns showed 65% nucleotide sequence homology with the authentic AAT gene, ATR appears to have been derived from a recent duplication of the AAT gene. It presumably represents a new member of the serine protease inhibitor superfamily.
Kelsey et al. (1988) determined that the ATR pseudogene spans about 5 kb.
Kelsey et al. (1988) mapped the SERPINA2P pseudogene about 10 kb downstream of the SERPINA1 gene.
Bao et al. (1988) determined that the SERPINA2P pseudogene is located about 8 kb downstream of the SERPINA1 gene.
Kalsheker and Watkins (1988) and others before them demonstrated RFLPs in the ATR sequence.
Rollini and Fournier (1997) presented a detailed restriction map of a 110-kb region of genomic DNA that includes the genes PI, PIL, and CDG (122500). They found that the 3 genes were in this order from telomere to centromere and that all 3 genes lie in a distal-to-proximal orientation. The PIL gene is approximately 12 kb downstream of the PI gene, which maps to 14q32.1, and CBG is approximately 57 kb downstream of PI. Earlier work on the mapping of these loci includes that of Sefton et al. (1990), Billingsley et al. (1993), and Byth et al. (1994). Rollini and Fournier (1997) stated that PIL is generally thought to be a pseudogene because it seems to lack promoter sequences and exon I, but that this issue was not clearly resolved.
Bao, J., Reed-Fourquet, L., Sifers, R. N., Kidd, V. J., Woo, S. L. C. Molecular structure and sequence homology of a gene related to alpha-1-antitrypsin in the human genome. Genomics 2: 165-173, 1988. [PubMed: 2842251] [Full Text: https://doi.org/10.1016/0888-7543(88)90099-7]
Billingsley, G. D., Walter, M. A., Hammond, G. L., Cox, D. W. Physical mapping of four serpin genes: alpha-1-antitrypsin, alpha-1-antichymotrypsin, corticosteroid-binding globulin, and protein C inhibitor, within a 280-kb region on chromosome 14q32.1. Am. J. Hum. Genet. 52: 343-353, 1993. [PubMed: 8381582]
Byth, B. C., Billingsley, G. D., Cox, D. W. Physical and genetic mapping of the serpin gene cluster at 14q32.1: allelic association and a unique haplotype associated with alpha-1-antitrypsin deficiency. Am. J. Hum. Genet. 55: 126-133, 1994. [PubMed: 7912884]
Kalsheker, N. A., Watkins, G. L. Heterozygosity and localisation of normal allelic fragments for an alpha-1-antitrypsin homologous sequence. Hum. Genet. 80: 108-109, 1988. [PubMed: 2901394] [Full Text: https://doi.org/10.1007/BF00451471]
Kelsey, G. D., Parkar, M., Povey, S. The human alpha-1-antitrypsin-related sequence gene: isolation and investigation of its expression. Ann. Hum. Genet. 52: 151-160, 1988. [PubMed: 2470331] [Full Text: https://doi.org/10.1111/j.1469-1809.1988.tb01091.x]
Lai, E. C., Kao, F.-T., Law, M. L., Woo, S. L. C. Assignment of the alpha-1-antitrypsin gene and a sequence-related gene to human chromosome 14 by molecular hybridization. Am. J. Hum. Genet. 35: 385-392, 1983. [PubMed: 6602546]
Rollini, P., Fournier, R. E. K. Molecular linkage of the human alpha-1-antitrypsin and corticosteroid-binding globulin genes on chromosome 14q32.1. Mammalian Genome 8: 913-916, 1997. [PubMed: 9383284] [Full Text: https://doi.org/10.1007/s003359900610]
Sefton, L., Kelsey, G., Kearney, P., Povey, S., Wolfe, J. A physical map of the human PI and AACT genes. Genomics 7: 382-388, 1990. [PubMed: 1973140] [Full Text: https://doi.org/10.1016/0888-7543(90)90172-q]