Gene Symbol: Pam
Description: peptidylglycine alpha-amidating monooxygenase
Alias: PHM, peptidyl-glycine alpha-amidating monooxygenase, PEPTIDYL-GLYCINE ALPHA-AMIDATING MONOOXYGENASE PRECURSOR (PAM)
Species: mouse
Products:     Pam

Top Publications

  1. Lossie A, Eipper B, Hand T, Camper S. Localization of the peptidylglycine alpha-amidating monooxygenase gene (Pam) introduces a region of homology between human chromosome 5q and mouse chromosome 1. Mamm Genome. 1994;5:738-9 pubmed
  2. Burmeister M, Ren Q, Makris G, Samson D, Bennett V. Genes for the neuronal immunoglobulin domain cell adhesion molecules neurofascin and Nr-CAM map to mouse chromosomes 1 and 12 and homologous human chromosomes. Mamm Genome. 1996;7:558-9 pubmed
  3. Ouafik L, Stoffers D, Campbell T, Johnson R, Bloomquist B, Mains R, et al. The multifunctional peptidylglycine alpha-amidating monooxygenase gene: exon/intron organization of catalytic, processing, and routing domains. Mol Endocrinol. 1992;6:1571-84 pubmed
    Peptidylglycine alpha-amidating monooxygenase (PAM; EC is a multifunctional protein containing two enzymes that act sequentially to catalyze the alpha-amidation of neuroendocrine peptides...
  4. Francone V, Ifrim M, Rajagopal C, Leddy C, Wang Y, Carson J, et al. Signaling from the secretory granule to the nucleus: Uhmk1 and PAM. Mol Endocrinol. 2010;24:1543-58 pubmed publisher
    ..Studies of peptidylglycine alpha-amidating monooxygenase (PAM), an essential secretory granule membrane enzyme, revealed a pathway that can relay information from secretory ..
  5. Bousquet Moore D, Prohaska J, Nillni E, Czyzyk T, Wetsel W, Mains R, et al. Interactions of peptide amidation and copper: novel biomarkers and mechanisms of neural dysfunction. Neurobiol Dis. 2010;37:130-40 pubmed publisher
    ..Using mice heterozygous for peptidylglycine alpha-amidating monooxygenase (PAM), a cuproenzyme essential for the synthesis of many neuropeptides, we identified alterations in anxiety-like ..
  6. Prohaska J, Gybina A, Broderius M, Brokate B. Peptidylglycine-alpha-amidating monooxygenase activity and protein are lower in copper-deficient rats and suckling copper-deficient mice. Arch Biochem Biophys. 2005;434:212-20 pubmed
    Peptidylglycine-alpha-amidating monooxygenase (PAM) is a copper-dependent enzyme involved in peptide posttranslational activation...
  7. Czyzyk T, Ning Y, Hsu M, Peng B, Mains R, Eipper B, et al. Deletion of peptide amidation enzymatic activity leads to edema and embryonic lethality in the mouse. Dev Biol. 2005;287:301-13 pubmed
    Peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the COOH-terminal amidation of peptide hormones. We previously had found high expression of PAM in several regions of the developing rodent...
  8. Prigge S, Mains R, Eipper B, Amzel L. New insights into copper monooxygenases and peptide amidation: structure, mechanism and function. Cell Mol Life Sci. 2000;57:1236-59 pubmed
    ..Peptidylglycine alpha-hydroxylating monooxygenase (PHM; EC 1.14.17...
  9. Guembe L, Villaro A, Treston A. Immunocytochemical mapping of the amidating enzyme PAM in the developing and adult mouse lung. J Histochem Cytochem. 1999;47:623-36 pubmed
    The enzyme PAM is required for activation of many peptide hormones. 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...

More Information


  1. Gaier E, Miller M, Ralle M, Aryal D, Wetsel W, Mains R, et al. Peptidylglycine ?-amidating monooxygenase heterozygosity alters brain copper handling with region specificity. J Neurochem. 2013;127:605-19 pubmed publisher
    ..the major intracellular Cu transporter in the brain, and its relation to peptidylglycine ?-amidating monooxygenase (PAM), an essential cuproenzyme and regulator of Cu homeostasis in neuroendocrine cells...
  2. Gaier E, Eipper B, Mains R. Pam heterozygous mice reveal essential role for Cu in amygdalar behavioral and synaptic function. Ann N Y Acad Sci. 2014;1314:15-23 pubmed publisher
    ..Mice deficient in the cuproenzyme peptidylglycine ?-amidating monooxygenase (Pam(+/-) mice) were initially generated to study neuropeptide amidation...
  3. Driscoll W, Hill D, Smalstig A, Mueller G. Murine atrial HL-1 cells express highly active peptidylglycine alpha-amidating enzyme. Peptides. 2006;27:1547-53 pubmed
    Peptidylglycine-alpha-hydroxylating monooxygenase (PHM; EC catalyzes the rate limiting step in peptide alpha-amidation, a posttranslational modification that is essential for receptor recognition and signal transduction...
  4. de Ledesma A, Desai A, Bolivar V, Symula D, Flaherty L. Two new behavioral QTLs, Emo4 and Reb1, map to mouse Chromosome 1: Congenic strains and candidate gene identification studies. Mamm Genome. 2006;17:111-8 pubmed
  5. Sobota J, Ferraro F, Bäck N, Eipper B, Mains R. Not all secretory granules are created equal: Partitioning of soluble content proteins. Mol Biol Cell. 2006;17:5038-52 pubmed
    ..We fused the soluble secretory protein peptidylglycine alpha-hydroxylating monooxygenase (PHM) to green fluorescent protein (GFP) to study granule formation...
  6. Bonnemaison M, Bäck N, Duffy M, Ralle M, Mains R, Eipper B. Adaptor Protein-1 Complex Affects the Endocytic Trafficking and Function of Peptidylglycine α-Amidating Monooxygenase, a Luminal Cuproenzyme. J Biol Chem. 2015;290:21264-79 pubmed publisher the trafficking of Atp7a, a copper-transporting P-type ATPase, and peptidylglycine α-amidating monooxygenase (PAM), a copper-dependent membrane enzyme...
  7. Nunes A, Liz M, Franquinho F, Teixeira L, Sousa V, Chenu C, et al. Neuropeptide Y expression and function during osteoblast differentiation--insights from transthyretin knockout mice. FEBS J. 2010;277:263-75 pubmed publisher
  8. Simpson P, Eipper B, Katz M, Gandara L, Wappner P, Fischer R, et al. Striking Oxygen Sensitivity of the Peptidylglycine α-Amidating Monooxygenase (PAM) in Neuroendocrine Cells. J Biol Chem. 2015;290:24891-901 pubmed publisher
    ..Peptidylglycine α-amidating monooxygenase (PAM) catalyzes a two-step reaction resulting in the C-terminal amidation of peptides, a process important for their ..
  9. Bousquet Moore D, Mains R, Eipper B. Peptidylgycine ?-amidating monooxygenase and copper: a gene-nutrient interaction critical to nervous system function. J Neurosci Res. 2010;88:2535-45 pubmed publisher
    Peptidylgycine alpha-amidating monooxygenase (PAM), a highly conserved copper-dependent enzyme, is essential for the synthesis of all amidated neuropeptides...
  10. Ayoub A, Oh S, Xie Y, Leng J, Cotney J, Dominguez M, et al. Transcriptional programs in transient embryonic zones of the cerebral cortex defined by high-resolution mRNA sequencing. Proc Natl Acad Sci U S A. 2011;108:14950-5 pubmed publisher
    ..Additionally, we found intergenic transcriptionally active regions that possibly encode unique zone-specific transcripts. Finally, we present a high-resolution transcriptome map of transient zones in the embryonic mouse forebrain. ..
  11. Kumar D, Strenkert D, Patel King R, Leonard M, Merchant S, Mains R, et al. A bioactive peptide amidating enzyme is required for ciliogenesis. elife. 2017;6: pubmed publisher
    ..We recently identified peptidylglycine α-amidating monooxygenase (PAM), an enzyme required for generating amidated bioactive signaling peptides, in Chlamydomonas and mammalian ..
  12. Yin P, Bousquet Moore D, Annangudi S, Southey B, Mains R, Eipper B, et al. Probing the production of amidated peptides following genetic and dietary copper manipulations. PLoS ONE. 2011;6:e28679 pubmed publisher
    ..hydroxyglycine-extended peptide) by the copper-dependent peptidylglycine-?-hydroxylating monooxygenase (PHM) domain of PAM...
  13. Gaier E, Rodriguiz R, Ma X, Sivaramakrishnan S, Bousquet Moore D, Wetsel W, et al. Haploinsufficiency in peptidylglycine alpha-amidating monooxygenase leads to altered synaptic transmission in the amygdala and impaired emotional responses. J Neurosci. 2010;30:13656-69 pubmed publisher
    ..Many neuropeptides require amidation for full activation by peptidylglycine ?-amidating monooxygenase (PAM), a transmembrane vesicular cuproenzyme and regulator of the secretory pathway...
  14. Yin L, Joshi S, Wu N, Tong X, Lazar M. E3 ligases Arf-bp1 and Pam mediate lithium-stimulated degradation of the circadian heme receptor Rev-erb alpha. Proc Natl Acad Sci U S A. 2010;107:11614-9 pubmed publisher
    ..Here we report that two E3 ligases, Arf-bp1 and Pam (Myc-bp2), are copurified with Rev-erb alpha and required for its ubiquitination...
  15. Wang G, Zhang J, Moskophidis D, Mivechi N. Targeted disruption of the heat shock transcription factor (hsf)-2 gene results in increased embryonic lethality, neuronal defects, and reduced spermatogenesis. Genesis. 2003;36:48-61 pubmed
    ..These findings suggest that hsf2 has a major function in controlling expression of genes important for embryonic development and maintenance of sperm production. ..
  16. Shirozu M, Tada H, Tashiro K, Nakamura T, Lopez N, Nazarea M, et al. Characterization of novel secreted and membrane proteins isolated by the signal sequence trap method. Genomics. 1996;37:273-80 pubmed
    ..These results indicate that the SST method is effective and useful for the isolation of secreted and membrane proteins without knowledge of their functions. ..
  17. Alam M, Caldwell B, Johnson R, Darlington D, Mains R, Eipper B. Novel proteins that interact with the COOH-terminal cytosolic routing determinants of an integral membrane peptide-processing enzyme. J Biol Chem. 1996;271:28636-40 pubmed
    The steady state distribution of membrane forms of peptidylglycine alpha-amidating monooxygenase (PAM) in the secretory pathway of neurons and endocrine cells depends on signals in its cytosolic COOH-terminal domain (CD)...