NLN (gene)
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| NLN | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | NLN, AGTBP, EP24.16, MEP, MOP, neurolysin | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 611530; MGI: 1923055; HomoloGene: 69315; GeneCards: NLN; OMA:NLN - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Neurolysin, mitochondrial is a protein that in humans is encoded by the NLN gene.[5][6] It is a 78-kDa enzyme, widely distributed in mammalian tissues and found in various subcellular locations that vary with cell type.[7] Neurolysin exemplifies the ability of neuropeptidases to target various cleavage site sequences by hydrolyzing them in vitro,[8][9] and metabolism of neurotensin is the most important role of neurolysin in vivo.[10] Neurolysin has also been implicated in pain control,[11][12][13] blood pressure regulation,[14][15] sepsis,[16] reproduction,[17][18] cancer biology[19] pathogenesis of stroke,[20] and glucose metabolism.[21]
Gene
The NLN gene lies on the chromosome location of 5q12.3 and consists of 14 exons.
Protein
Neurolysin, with 704 amino acid residues, is a zinc metalloendopeptidase with a conserved HEXXH motif. It has an overall prolate ellipsoid shape, with a deep narrow channel dividing it into two roughly equal domains.[22] The catalytic site is contained within a thermolysin-like region found in many metallopeptidases and located in the domain near the floor of the channel.[10][23]
Function
Neurolysin hydrolyzes only peptides containing 5-17 amino acids by cleaving at a limited set of sites.[22][24][25] The specificity of neurolysin for small bioactive peptides is due to the presence of large structural elements erected over its active site region that allow substrates access only through a deep narrow channel.[26] In vitro, neurolysin exemplifies the ability of some neuropeptidases to target diverse cleavage site sequences.[8][9] In vivo, their most established role is cleaving neurotensin between its 10th and 11th residues to produce inactive fragments and it has been recently identified as a non-AT1-non-AT2 angiotensin-binding site, with function pertaining to the rennin-angiotensin system.[10][27][28] Neurotensin is involved in many processes including mast cell degranulation and regulation of central nervous system dopaminergic and cholinergic circuits.[29][30][31] A lower level of neurotensin is associated with schizophrenia,[32] and it is implicated in cardiovascular disorders, addiction, Huntington disease and Parkinson disease.[30][33][34][35] Neurotensin is also one of the most potent blockers of pain perception.[36]
Clinical significance
Metabolism of neurotensin is the most important role of neurolysin in vivo and has been identified as a non-AT1-non-AT2 angiotensin-binding site.[10][27][28] Neurotensin is involved in many processes including mast cell degranullation and regulation of central nervous system dopaminergic and cholinergic circuits.[29][30][31] Neurolysin has also been implicated in pain control,[11][12][13] blood pressure regulation,[14][15] sepsis,[16] reproduction,[17][18] cancer biology,[19] pathogenesis of stroke,[20] and glucose metabolism.[21] Inhibition of neurolysin has been shown to produce neurotensin-induced analgesia in mice,[37] and control of neurotensin levels by neurolysin may serve as a potential target for antipsychotic therapies.
