Pathway Component Details
| Name: | Amidating Enzyme |
| Definition: | About half of the known bioactive peptides are α-amidated, and α-amidation is generally crucial to biological potency. The peptidyl-Gly and peptide-COOH forms are usually inactive at physiological concentrations. The first step of the α-amidation reaction is performed by peptidylglycine α-hydroxylating mono-oxygenase (PHM), which is the NH2-terminal portion of the bifunctional PAM protein. PHM binds two Cu2+ atoms that participate in catalysis by undergoing cycles of reduction and oxidation. PHM uses ascorbic acid as the reductant, with one atom of oxygen from O2 incorporated into the peptide during the hydroxylation step. Thus, PHM is enzymatically very similar to dopamine β-mono-oxygenase (DBM), which converts dopamine to norepinephrine (see Chap. 12). The second step of the α-amidation reaction is performed by a second enzymatic domain of PAM, peptidyl-α-hydroxyglycine α-amidating lyase (PAL). The PAL domain constitutes a novel, divalent metal ion-dependent enzyme. Neurons primarily express an integral membrane form of the bifunctional PAM protein (Fig. 18-5), while an additional mRNA-splicing event enables some endocrine cells to express soluble versions of the protein, lacking the transmembrane domain. In the integral membrane forms of PAM, the short COOH-terminal domain extends into the cytoplasm and participates in the routing of PAM between LDCVs and the cell surface. The supply of reduced ascorbate in LDCVs is maintained by cytochrome B561, a protein that has five transmembrane domains and shuttles electrons from cytosolic ascorbate to ascorbate in the lumen of the LDCVs [16]. Cytochrome B561 is also found in catecholamine-containing vesicles, where it performs a similar function for DBM (see Chap. 12). Nervous and endocrine tissues maintain concentrations of reduced ascorbate about 100-fold above the blood concentration of ascorbate, while most other tissues do not concentrate ascorbate. |
| Category ID: | P04599 |
| Synonyms: | |
| Upstream: | |
| Downstream: |
Pro2-Vasopressin
Vasopressin |
| Number Families/Subfamilies: | 4 |
| Number of Associated Sequences: | 15 |
| GO Molecular Function: |
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| GO Biological Process: |
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| GO Cellular Component: |
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| PANTHER protein class: |
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| References: | http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid |
Sequence Association
| Panther Subfamily | Associated Sequence | Definition | Confidence Code | Evidence |
| PTHR10680:SF14 | F1MZB4 | Peptidylglycine alpha-amidating monooxygenase | IC | PubMed:3153462 |
| H2R5G8 | Peptidylglycine alpha-amidating monooxygenase | ISS | PubMed:3153462 | |
| I0FS58 | Peptidyl-glycine alpha-amidating monooxygenase isoform a preproprotein | ISS | PubMed:3153462 | |
| O01404 | Peptidylglycine alpha-hydroxylating monooxygenase | IC | PubMed:3153462 | |
| P14925 | Peptidylglycine alpha-amidating monooxygenase | IC | PubMed:3153462 | |
| P19021 | Peptidyl-glycine alpha-amidating monooxygenase | IC | PubMed:3153462 | |
| P83388 | Probable peptidyl-glycine alpha-amidating monooxygenase pamn-1 | IC | PubMed:3153462 | |
| P97467 | Peptidyl-glycine alpha-amidating monooxygenase | IC | PubMed:3153462 | |
| PTHR10680:SF36 | P91268 | Probable peptidyl-alpha-hydroxyglycine alpha-amidating lyase pgal-1 | IC | PubMed:3153462 |
| Q9V5E1 | Peptidyl-alpha-hydroxyglycine alpha-amidating lyase 1 | IC | PubMed:3153462 | |
| PTHR10680:SF37 | Q9W1L5 | Peptidyl-alpha-hydroxyglycine alpha-amidating lyase 2 | IC | PubMed:3153462 |
| PTHR24104:SF31 | H2Q7G1 | NHL repeat containing 3 | ISS | |
| Q5JS37 | NHL repeat-containing protein 3 | IC |
