NLN (gene)

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Template:Cs1 config Template:Short description Template:Infobox gene Neurolysin, mitochondrial is a protein that in humans is encoded by the NLN gene.[1][2] It is a 78-kDa enzyme, widely distributed in mammalian tissues and found in various subcellular locations that vary with cell type.[3] Neurolysin exemplifies the ability of neuropeptidases to target various cleavage site sequences by hydrolyzing them in vitro,[4][5] and metabolism of neurotensin is the most important role of neurolysin in vivo.[6] Neurolysin has also been implicated in pain control,[7][8][9] blood pressure regulation,[10][11] sepsis,[12] reproduction,[13][14] cancer biology[15] pathogenesis of stroke,[16] and glucose metabolism.[17]

Structure

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.[18] 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.[6][19]

Function

Neurolysin hydrolyzes only peptides containing 5-17 amino acids by cleaving at a limited set of sites.[18][20][21] 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.[22] In vitro, neurolysin exemplifies the ability of some neuropeptidases to target diverse cleavage site sequences.[4][5] 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.[6][23][24] Neurotensin is involved in many processes including mast cell degranulation and regulation of central nervous system dopaminergic and cholinergic circuits.[25][26][27] A lower level of neurotensin is associated with schizophrenia,[28] and it is implicated in cardiovascular disorders, addiction, Huntington disease and Parkinson disease.[26][29][30][31] Neurotensin is also one of the most potent blockers of pain perception.[32]

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.[6][23][24] Neurotensin is involved in many processes including mast cell degranullation and regulation of central nervous system dopaminergic and cholinergic circuits.[25][26][27] Neurolysin has also been implicated in pain control,[7][8][9] blood pressure regulation,[10][11] sepsis,[12] reproduction,[13][14] cancer biology,[15] pathogenesis of stroke,[16] and glucose metabolism.[17] Inhibition of neurolysin has been shown to produce neurotensin-induced analgesia in mice,[33] and control of neurotensin levels by neurolysin may serve as a potential target for antipsychotic therapies.

Interactions

This protein is known to interact with:

References

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Further reading

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