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Gene Review

Pam  -  peptidylglycine alpha-amidating monooxygenase

Mus musculus

Synonyms: PAM, PHM, Peptidyl-glycine alpha-amidating monooxygenase
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Disease relevance of Pam


High impact information on Pam


Chemical compound and disease context of Pam


Biological context of Pam

  • Localization of the peptidylglycine alpha-amidating monooxygenase gene (Pam) introduces a region of homology between human chromosome 5q and mouse chromosome 1 [13].
  • No peptide amidation activity was detected in PAM mutant embryos, and there was no moderation of the AM-like phenotype that could be expected if any alternative peptide amidation mechanism exists in the mouse [14].
  • To determine the function of PAM during mouse embryogenesis, we produced a null mutant of the PAM gene [14].
  • In 12-day-old (P12) mouse pups derived from dams that began Cu deficiency on day 7 of gestation, there was a parallel reduction in brain PAM activity and protein of 40-50% [15].
  • The exon following the PAL domain encodes the trans-membrane domain of PAM; alternative splicing at this site produces integral membrane or soluble PAM proteins [16].

Anatomical context of Pam

  • These defects include thinning of the aorta and carotid arteries and are very similar to those of the recently characterized adrenomedullin (AM) gene KO despite the presence of elevated immunoreactive AM in PAM KO embryos [14].
  • In adult mouse lung, immunostaining for PAM was located in Clara cells, which constitute most of the epithelial cells of the mouse bronchial/bronchiolar tree [17].
  • Smooth muscle of airways and blood vessels, and some parenchymal cells, probably macrophages, also showed PAM immunoreactivity [17].
  • No reduction in Cu- rat midbrain PAM protein was detected although PAM activity was reduced 40% [15].
  • Short-term DETC lines were 35S-labeled and tested for migration toward Pam 212 keratinocyte culture supernatants using a modified Boyden chamber method; cell movement from upper chambers toward test samples in lower chambers was traced by counting radioactivity [18].

Associations of Pam with chemical compounds

  • Chemotactic activities were 1) produced by Pam 212 cells even in the absence of serum; 2) greater than 12 kD in size; 3) heat and pH labile; 4) trypsin sensitive; and 5) precipitated by 60-100% ammonium sulfate [18].
  • Preincubation of the PAM 212 cells with cycloheximide prevented attachment [1].
  • The bifunctional PAM protein contains an NH2-terminal monooxygenase (PHM) domain followed by a lyase (PAL) domain and a transmembrane domain [19].
  • It was equally effective in inhibiting the growth of the murine L1210 line and of a subline (L1210/PAM) resistant to nitrogen mustards, whereas distamycin A was virtually inactive [20].
  • Peptidylglycine alpha-amidating monooxygenase is a copper- and ascorbate-dependent enzyme that converts peptides with COOH-terminal glycine residues into the corresponding alpha-amidated product peptides [21].

Other interactions of Pam


Analytical, diagnostic and therapeutic context of Pam


  1. Role of laminin in the attachment of PAM 212 (epithelial) cells to basement membrane collagen. Terranova, V.P., Rohrbach, D.H., Martin, G.R. Cell (1980) [Pubmed]
  2. Effect of psoralen plus ultraviolet A radiation on in vivo growth of melanoma cells. Aubin, F., Donawho, C.K., Kripke, M.L. Cancer Res. (1991) [Pubmed]
  3. Growth regulated oncogene-alpha expression by murine squamous cell carcinoma promotes tumor growth, metastasis, leukocyte infiltration and angiogenesis by a host CXC receptor-2 dependent mechanism. Loukinova, E., Dong, G., Enamorado-Ayalya, I., Thomas, G.R., Chen, Z., Schreiber, H., Van Waes, C. Oncogene (2000) [Pubmed]
  4. PAM cell assay as a tests for multiple-sclerosis associated agent. Gravell, M., Hamilton, R.S., Kiefer, R.H., Madden, D.L., Sever, J.L., Tourtellotte, W.W. Neurology (1978) [Pubmed]
  5. Scrapie in vitro: agent replication and reduced cell yield. Carp, R.I., Merz, G.S., Licursi, P.C. Infect. Immun. (1976) [Pubmed]
  6. Synthesis of leukotriene C and other arachidonic acid metabolites by mouse pulmonary macrophages. Rouzer, C.A., Scott, W.A., Hamill, A.L., Cohn, Z.A. J. Exp. Med. (1982) [Pubmed]
  7. Expression and modulation of nerve growth factor in murine keratinocytes (PAM 212). Tron, V.A., Coughlin, M.D., Jang, D.E., Stanisz, J., Sauder, D.N. J. Clin. Invest. (1990) [Pubmed]
  8. Ascorbate transport by AtT20 mouse pituitary corticotropic tumor cells: uptake and secretion studies. Shields, P.P., Gibson, T.R., Glembotski, C.C. Endocrinology (1986) [Pubmed]
  9. Oleic acid derived metabolites in mouse neuroblastoma N18TG2 cells. Merkler, D.J., Chew, G.H., Gee, A.J., Merkler, K.A., Sorondo, J.P., Johnson, M.E. Biochemistry (2004) [Pubmed]
  10. Central activity of acetylcholinesterase oxime reactivators. Clement, J.G. Toxicol. Appl. Pharmacol. (1992) [Pubmed]
  11. Effects of the novel alphav integrin antagonist SM256 and cis-platinum on growth of murine squamous cell carcinoma PAM LY8. Van Waes, C., Enamorado-Ayala, I., Hecht, D., Sulica, L., Chen, Z., Batt, D.G., Mousa, S. Int. J. Oncol. (2000) [Pubmed]
  12. Lethal photosensitization by endogenous porphyrins of PAM cells--modification by desferrioxamine. Ortel, B., Tanew, A., Hönigsmann, H. J. Photochem. Photobiol. B, Biol. (1993) [Pubmed]
  13. Localization of the peptidylglycine alpha-amidating monooxygenase gene (Pam) introduces a region of homology between human chromosome 5q and mouse chromosome 1. Lossie, A.C., Eipper, B.A., Hand, T.A., Camper, S.A. Mamm. Genome (1994) [Pubmed]
  14. Deletion of peptide amidation enzymatic activity leads to edema and embryonic lethality in the mouse. Czyzyk, T.A., Ning, Y., Hsu, M.S., Peng, B., Mains, R.E., Eipper, B.A., Pintar, J.E. Dev. Biol. (2005) [Pubmed]
  15. Peptidylglycine-alpha-amidating monooxygenase activity and protein are lower in copper-deficient rats and suckling copper-deficient mice. Prohaska, J.R., Gybina, A.A., Broderius, M., Brokate, B. Arch. Biochem. Biophys. (2005) [Pubmed]
  16. The multifunctional peptidylglycine alpha-amidating monooxygenase gene: exon/intron organization of catalytic, processing, and routing domains. Ouafik, L.H., Stoffers, D.A., Campbell, T.A., Johnson, R.C., Bloomquist, B.T., Mains, R.E., Eipper, B.A. Mol. Endocrinol. (1992) [Pubmed]
  17. Immunocytochemical mapping of the amidating enzyme PAM in the developing and adult mouse lung. Guembe, L., Villaro, A.C., Treston, A.M. J. Histochem. Cytochem. (1999) [Pubmed]
  18. Mouse dendritic epidermal T cells exhibit chemotactic migration toward PAM 212 keratinocyte culture supernatants. Chung, B.S., Bergstresser, P.R., Takashima, A. J. Invest. Dermatol. (1993) [Pubmed]
  19. Induction of integral membrane PAM expression in AtT-20 cells alters the storage and trafficking of POMC and PC1. Ciccotosto, G.D., Schiller, M.R., Eipper, B.A., Mains, R.E. J. Cell Biol. (1999) [Pubmed]
  20. Selective DNA interaction of the novel distamycin derivative FCE 24517. Broggini, M., Erba, E., Ponti, M., Ballinari, D., Geroni, C., Spreafico, F., D'Incalci, M. Cancer Res. (1991) [Pubmed]
  21. Inhibition of peptide amidation by disulfiram and diethyldithiocarbamate. Mains, R.E., Park, L.P., Eipper, B.A. J. Biol. Chem. (1986) [Pubmed]
  22. Menkes protein contributes to the function of peptidylglycine alpha-amidating monooxygenase. Steveson, T.C., Ciccotosto, G.D., Ma, X.M., Mueller, G.P., Mains, R.E., Eipper, B.A. Endocrinology (2003) [Pubmed]
  23. Differential effects of temperature blockade on the proteolytic processing of three secretory granule-associated proteins. Milgram, S.L., Mains, R.E. J. Cell. Sci. (1994) [Pubmed]
  24. Plasma peptidylglycine alpha-amidating monooxygenase (PAM) and ceruloplasmin are affected by age and copper status in rats and mice. Prohaska, J.R., Broderius, M. Comp. Biochem. Physiol. B, Biochem. Mol. Biol. (2006) [Pubmed]
  25. Expression of individual forms of peptidylglycine alpha-amidating monooxygenase in AtT-20 cells: endoproteolytic processing and routing to secretory granules. Milgram, S.L., Johnson, R.C., Mains, R.E. J. Cell Biol. (1992) [Pubmed]
  26. Differential trafficking of soluble and integral membrane secretory granule-associated proteins. Milgram, S.L., Eipper, B.A., Mains, R.E. J. Cell Biol. (1994) [Pubmed]
  27. Macrophage colony-stimulating factor production by murine and human keratinocytes. Enhancement by bacterial lipopolysaccharide. Chodakewitz, J.A., Lacy, J., Edwards, S.E., Birchall, N., Coleman, D.L. J. Immunol. (1990) [Pubmed]
  28. In vivo cutaneous interferon-gamma gene delivery using novel dicationic (gemini) surfactant-plasmid complexes. Badea, I., Verrall, R., Baca-Estrada, M., Tikoo, S., Rosenberg, A., Kumar, P., Foldvari, M. The journal of gene medicine. (2005) [Pubmed]
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