NLN (gene)

NLN
Identifiers
Aliases	NLN, AGTBP, EP24.16, MEP, MOP, neurolysin
External IDs	OMIM: 611530; MGI: 1923055; HomoloGene: 69315; GeneCards: NLN; OMA:NLN - orthologs
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q12.3 Start 65,722,205 bp[1] End 65,871,725 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13|13 D1 Start 104,159,565 bp[2] End 104,246,122 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in endothelial cell secondary oocyte tibialis anterior muscle mucosa of ileum pancreatic ductal cell stromal cell of endometrium monocyte gastrocnemius muscle deltoid muscle ganglionic eminence Top expressed in tail of embryo genital tubercle superior cervical ganglion Rostral migratory stream spermatocyte blastocyst secondary oocyte cumulus cell left lobe of liver fossa More reference expression data BioGPS n/a
Gene ontology Molecular function peptide binding peptidase activity hydrolase activity metallopeptidase activity metal ion binding metalloendopeptidase activity Cellular component cytoplasm mitochondrial intermembrane space plasma membrane mitochondrion extracellular region Biological process regulation of gluconeogenesis regulation of skeletal muscle fiber differentiation proteolysis peptide metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 57486 75805 Ensembl ENSG00000123213 ENSMUSG00000021710 UniProt Q9BYT8 Q91YP2 RefSeq (mRNA) NM_020726 NM_029447 RefSeq (protein) NP_065777 NP_083723 Location (UCSC) Chr 5: 65.72 – 65.87 Mb Chr 13: 104.16 – 104.25 Mb PubMed search [3] [4]
Wikidata
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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]

The NLN gene lies on the chromosome location of 5q12.3 and consists of 14 exons.

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]

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]

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.

This protein is known to interact with:

• Neurotensin^[10][16]
• HIV-1^[38]