Peptidylglycine alpha-amidating monooxygenase

PAM

Identifiers

PAM, PAL, PHM, Peptidylglycine alpha-amidating monooxygenase

External IDs

MGI: 97475 HomoloGene: 37369 GeneCards: PAM

Gene ontology
Molecular function	• metal ion binding • calcium ion binding • copper ion binding • lyase activity • protein kinase binding • monooxygenase activity • catalytic activity • oxidoreductase activity • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced ascorbate as one donor, and incorporation of one atom of oxygen • L-ascorbic acid binding • protein binding • zinc ion binding • peptidylglycine monooxygenase activity • peptidylamidoglycolate lyase activity
Cellular component	• extracellular exosome • extracellular region • integral component of membrane • trans-Golgi network • extracellular fluid • neuron projection • cell surface • neuronal cell body • perinuclear region of cytoplasm • plasma membrane • secretory granule membrane • secretory granule • perikaryon • membrane
Biological process	• response to hypoxia • limb development • ovulation cycle process • odontogenesis • regulation of protein secretion • response to estradiol • regulation of actin cytoskeleton organization • maternal process involved in female pregnancy • regulation of transcription from RNA polymerase II promoter • metabolic process • protein homooligomerization • response to copper ion • heart development • central nervous system development • toxin metabolic process • response to pH • response to glucocorticoid • protein amidation • protein metabolic process • oxidation-reduction process • long-chain fatty acid metabolic process • peptide metabolic process • response to drug • lactation • peptide amidation
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

Entrez


5066


18484

Ensembl


ENSG00000145730


ENSMUSG00000026335

UniProt


P19021


P97467

RefSeq (mRNA)

NM_000919 NM_001177306 NM_138766 NM_138821 NM_138822
NM_001319943


NM_013626

RefSeq (protein)

NP_000910.2 NP_001170777.1 NP_620121.1 NP_620176.1 NP_620177.1
NP_001306872.1


NP_038654.2

Location (UCSC)

Chr 5: 102.75 – 103.03 Mb

Chr 1: 97.8 – 98.1 Mb

PubMed search

^[1]

^[2]

Wikidata

View/Edit Human

View/Edit Mouse

Peptidyl-glycine alpha-amidating monooxygenase is an enzyme that, in humans, is encoded by the PAM gene.^[3]^[4]

Function

This gene encodes a multifunctional protein. It has two enzymatically active domains with catalytic activities - peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL). These catalytic domains work sequentially to catalyze neuroendocrine peptides to active alpha-amidated products. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene, but some of their full-length sequences are not yet known.^[4]

References

↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ Glauder J, Ragg H, Rauch J, Engels JW (Jul 1990). "Human peptidylglycine alpha-amidating monooxygenase: cDNA, cloning and functional expression of a truncated form in COS cells". Biochem Biophys Res Commun. 169 (2): 551–8. doi:10.1016/0006-291X(90)90366-U. PMID 2357221.
1 2 "Entrez Gene: PAM peptidylglycine alpha-amidating monooxygenase".

Pittner RA, Albrandt K, Beaumont K, Gaeta LS, Koda JE, Moore CX, Rittenhouse J, Rink TJ (1994). "Molecular physiology of amylin.". J. Cell. Biochem. 55 Suppl (S1994A): 19–28. doi:10.1002/jcb.240550004. PMID 7929615.
Eipper BA, Milgram SL, Husten EJ, Yun HY, Mains RE (1993). "Peptidylglycine alpha-amidating monooxygenase: a multifunctional protein with catalytic, processing, and routing domains.". Protein Sci. 2 (4): 489–97. doi:10.1002/pro.5560020401. PMC 2142366. PMID 8518727.
Ouafik LH, Stoffers DA, Campbell TA, Johnson RC, Bloomquist BT, Mains RE, Eipper BA (1992). "The multifunctional peptidylglycine alpha-amidating monooxygenase gene: exon/intron organization of catalytic, processing, and routing domains.". Mol. Endocrinol. 6 (10): 1571–84. doi:10.1210/me.6.10.1571. PMID 1448112.
Maltese JY, Eipper BA (1993). "Developmental expression of peptidylglycine alpha-amidating monooxygenase (PAM) in primary cultures of neonatal rat cardiocytes: a model for studying regulation of PAM expression in the rat heart.". Mol. Endocrinol. 6 (12): 1998–2008. doi:10.1210/me.6.12.1998. PMID 1491686.
Braas KM, Harakall SA, Ouafik L, Eipper BA, May V (1992). "Expression of peptidylglycine alpha-amidating monooxygenase: an in situ hybridization and immunocytochemical study.". Endocrinology. 130 (5): 2778–88. doi:10.1210/en.130.5.2778. PMID 1572293.
Roberts AN, Leighton B, Todd JA, Cockburn D, Schofield PN, Sutton R, Holt S, Boyd Y, Day AJ, Foot EA (1990). "Molecular and functional characterization of amylin, a peptide associated with type 2 diabetes mellitus.". Proc. Natl. Acad. Sci. U.S.A. 86 (24): 9662–6. doi:10.1073/pnas.86.24.9662. PMC 298561. PMID 2690069.
Vos MD, Jones JE, Treston AM (1995). "Human peptidylglycine alpha-amidating monooxygenase transcripts derived by alternative mRNA splicing of an unreported exon.". Gene. 163 (2): 307–11. doi:10.1016/0378-1119(95)00364-C. PMID 7590286.
Tsukamoto T, Noguchi M, Kayama H, Watanabe T, Asoh T, Yamamoto T (1995). "Increased peptidylglycine alpha-amidating monooxygenase activity in cerebrospinal fluid of patients with multiple sclerosis.". Intern. Med. 34 (4): 229–32. doi:10.2169/internalmedicine.34.229. PMID 7606087.
Yun HY, Johnson RC, Mains RE, Eipper BA (1993). "Topological switching of the COOH-terminal domain of peptidylglycine alpha-amidating monooxygenase by alternative RNA splicing.". Arch. Biochem. Biophys. 301 (1): 77–84. doi:10.1006/abbi.1993.1117. PMID 7680192.
Mains RE, Milgram SL, Keutmann HT, Eipper BA (1995). "The NH2-terminal proregion of peptidylglycine alpha-amidating monooxygenase facilitates the secretion of soluble proteins.". Mol. Endocrinol. 9 (1): 3–13. doi:10.1210/me.9.1.3. PMID 7760848.
Tateishi K, Arakawa F, Misumi Y, Treston AM, Vos M, Matsuoka Y (1995). "Isolation and functional expression of human pancreatic peptidylglycine alpha-amidating monooxygenase.". Biochem. Biophys. Res. Commun. 205 (1): 282–90. doi:10.1006/bbrc.1994.2662. PMID 7999037.
Martínez A, Montuenga LM, Springall DR, Treston A, Cuttitta F, Polak JM (1993). "Immunocytochemical localization of peptidylglycine alpha-amidating monooxygenase enzymes (PAM) in human endocrine pancreas.". J. Histochem. Cytochem. 41 (3): 375–80. doi:10.1177/41.3.8094086. PMID 8094086.
Kapuscinski M, Green M, Sinha SN, Shepherd JJ, Shulkes A (1993). "Peptide alpha-amidation activity in human plasma: relationship to gastrin processing.". Clin. Endocrinol. (Oxf). 39 (1): 51–8. doi:10.1111/j.1365-2265.1993.tb01750.x. PMID 8102327.
Yun HY, Keutmann HT, Eipper BA (1994). "Alternative splicing governs sulfation of tyrosine or oligosaccharide on peptidylglycine alpha-amidating monooxygenase.". J. Biol. Chem. 269 (14): 10946–55. PMID 8144680.
Ouafik LH, Mattei MG, Giraud P, Oliver C, Eipper BA, Mains RE (1994). "Localization of the gene encoding peptidylglycine alpha-amidating monooxygenase (PAM) to human chromosome 5q14-5q21.". Genomics. 18 (2): 319–21. doi:10.1006/geno.1993.1471. PMID 8288234.
Husten EJ, Tausk FA, Keutmann HT, Eipper BA (1993). "Use of endoproteases to identify catalytic domains, linker regions, and functional interactions in soluble peptidylglycine alpha-amidating monooxygenase.". J. Biol. Chem. 268 (13): 9709–17. PMID 8486658.
Yun HY, Milgram SL, Keutmann HT, Eipper BA (1996). "Phosphorylation of the cytosolic domain of peptidylglycine alpha-amidating monooxygenase.". J. Biol. Chem. 270 (50): 30075–83. doi:10.1074/jbc.270.50.30075. PMID 8530412.
Morris KM, Cao F, Onagi H, Altamore TM, Gamble AB, Easton CJ (1 December 2012). "Prohormone-substrate peptide sequence recognition by peptidylglycine α-amidating monooxygenase and its reflection in increased glycolate inhibitor potency". Bioorganic & Medicinal Chemistry Letters. 22 (23): 7015–7018. doi:10.1016/j.bmcl.2012.10.004. PMID 23084901.
McIntyre NR, Lowe EW, Belof JL, Ivkovic M, Shafer J, Space B, Merkler DJ (2 November 2010). "Evidence for substrate preorganization in the peptidylglycine α-amidating monooxygenase reaction describing the contribution of ground state structure to hydrogen tunneling". Journal of the American Chemical Society. 132 (46): 16393–16402. doi:10.1021/ja1019194. PMC 2988104. PMID 21043511.

PDB gallery

1opm: OXIDIZED (CU2+) PEPTIDYLGLYCINE ALPHA-HYDROXYLATING MONOOXYGENASE (PHM) WITH BOUND SUBSTRATE

1phm: PEPTIDYLGLYCINE ALPHA-HYDROXYLATING MONOOXYGENASE (PHM) FROM RAT

1sdw: Reduced (Cu+) peptidylglycine alpha-hydroxylating monooxygenase with bound peptide and dioxygen

1yi9: Crystal Structure Analysis of the oxidized form of the M314I mutant of Peptidylglycine alpha-Hydroxylating Monooxygenase

1yip: Oxidized Peptidylglycine Alpha-Hydroxylating Monooxygenase (PHM) in a New Crystal Form

1yjk: Reduced Peptidylglycine Alpha-Hydroxylating Monooxygenase (PHM) in a New Crystal Form

1yjl: Reduced Peptidylglycine alpha-Hydroxylating Monooxygenase in a new crystal form

3phm: REDUCED (CU+) PEPTIDYLGLYCINE ALPHA-HYDROXYLATING MONOOXYGENASE (PHM)

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Peptidylglycine alpha-amidating monooxygenase

Function

References

Further reading