HGNC Approved Gene Symbol: PAM
Cytogenetic location: 5q21.1 Genomic coordinates (GRCh38): 5:102,754,783-103,031,105 (from NCBI)
Peptidylglycine alpha-amidating monooxygenase (EC 1.14.17.3) is a multifunctional protein containing 2 enzymes, peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL), that act sequentially to catalyze the alpha-amidation of neuroendocrine peptides (Ouafik et al., 1993).
Glauder et al. (1990) showed that alternative splicing generates 2 forms of PAM mRNA in humans.
By screening rat atrium and pituitary cDNA libraries, Eipper et al. (1992) identified 7 Pam splice variants. Five of the variants encode bifunctional Pam proteins, including 3 variants encoding Pam proteins with a transmembrane domain and 2 encoding soluble bifunctional proteins. The other 2 variants encode a soluble form of Phm and an inactive, truncated Phm protein. Further analysis showed that both alternative splicing and posttranslational processing contribute to tissue-specific production of proteins derived from Pam in rat.
Ouafik et al. (1993) used Southern blot analysis of human placental DNA to demonstrate that PAM is encoded by a single gene. By somatic cell hybridization, Ouafik et al. (1992) mapped the human PAM gene to the long arm of chromosome 5. By in situ hybridization, Ouafik et al. (1993) regionalized the assignment to 5q14-q21. They noted that the NEC1 gene (PCSK1; 162150), which encodes another enzyme important in posttranslational processing of neuroendocrine precursors, prohormone convertase 1 (PC1), is located in the same region (5q15-q21).
Gross (2021) mapped the PAM gene to chromosome 5q21.1 based on an alignment of the PAM sequence (GenBank AF010472) with the genomic sequence (GRCh38).
Using RFLPs, Lossie et al. (1994) mapped the Pam gene to mouse chromosome 1 in 3 individual backcrosses.
Eipper, B. A., Green, C. B.-R., Campbell, T. A., Stoffers, D. A., Keutmann, H. T., Mains, R. E., Ouafik, L.'H. Alternative splicing and endoproteolytic processing generate tissue-specific forms of pituitary peptidylglycine alpha-amidating monooxygenase (PAM). J. Biol. Chem. 267: 4008-4015, 1992. [PubMed: 1740449]
Glauder, J., Ragg, H., Rauch, J., Engels, J. W. Human peptidylglycine alpha-amidating monooxygenase: cDNA, cloning and functional expression of a truncated form in COS cells. Biochem. Biophys. Res. Commun. 169: 551-558, 1990. [PubMed: 2357221] [Full Text: https://doi.org/10.1016/0006-291x(90)90366-u]
Gross, M. B. Personal Communication. Baltimore, Md. 5/17/2021.
Lossie, A. C., Eipper, B. A., Hand, T. A., Camper, S. A. Localization of the peptidylglycine alpha-amidating monooxygenase gene (Pam) introduces a region of homology between human chromosome 5q and mouse chromosome 1. Mammalian Genome 5: 738-739, 1994. [PubMed: 7873888] [Full Text: https://doi.org/10.1007/BF00426085]
Ouafik, L'H., Mattei, M. G., Giraud, P., Oliver, C., Eipper, B. A., Mains, R. E. Localization of the gene encoding peptidylglycine alpha-amidating monooxygenase (PAM) to human chromosome 5q14-5q21. Genomics 18: 319-321, 1993. [PubMed: 8288234] [Full Text: https://doi.org/10.1006/geno.1993.1471]
Ouafik, L'H., Stoffers, D. A., Campbell, T. A., Johnson, R. C., Bloomquist, B. T., Mains, R. E., Eipper, B. A. The multifunctional peptidylglycine alpha-amidating monooxygenase gene: exon/intron organization of catalytic, processing, and routing domains. Molec. Endocr. 6: 1571-1584, 1992. [PubMed: 1448112] [Full Text: https://doi.org/10.1210/mend.6.10.1448112]