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    NLN neurolysin [ Homo sapiens (human) ]

    Gene ID: 57486, updated on 28-Oct-2024

    Summary

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    Official Symbol
    NLNprovided by HGNC
    Official Full Name
    neurolysinprovided by HGNC
    Primary source
    HGNC:HGNC:16058
    See related
    Ensembl:ENSG00000123213 MIM:611530; AllianceGenome:HGNC:16058
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MEP; MOP; AGTBP; EP24.16
    Summary
    This gene encodes a member of the metallopeptidase M3 protein family that cleaves neurotensin at the Pro10-Tyr11 bond, leading to the formation of neurotensin(1-10) and neurotensin(11-13). The encoded protein is likely involved in the termination of the neurotensinergic signal in the central nervous system and in the gastrointestinal tract.[provided by RefSeq, Jun 2010]
    Expression
    Ubiquitous expression in liver (RPKM 3.9), brain (RPKM 3.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NLN in Genome Data Viewer
    Location:
    5q12.3
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (65722205..65829283)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (66543992..66651091)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (65018032..65125111)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22607 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22608 Neighboring gene RNA, U6 small nuclear 540, pseudogene Neighboring gene tripartite motif containing 23 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:64934876-64935323 Neighboring gene trafficking protein particle complex subunit 13 Neighboring gene shieldin complex subunit 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22609 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:65015266-65015462 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16058 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16057 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16056 Neighboring gene small glutamine rich tetratricopeptide repeat co-chaperone beta Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:65018623-65019444 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16059 Neighboring gene PRAME family member 17 pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16060 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:65220503-65221127 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:65221752-65222376 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22612 Neighboring gene LSM3 homolog, U6 small nuclear RNA associated (S. cerevisiae) pseudogene Neighboring gene small nucleolar RNA SNORA76 Neighboring gene erbb2 interacting protein

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Structural basis of divergent substrate recognition and inhibition of human neurolysin. Shi K, et al. Sci Rep, 2024 Aug 8. PMID 39117724, Free PMC Article
    2. Confocal microscopy reveals thimet oligopeptidase (EC 3.4.24.15) and neurolysin (EC 3.4.24.16) in the classical secretory pathway. Garrido PA, et al. DNA Cell Biol, 1999 Apr. PMID 10235115
    3. Mechanism of Peptide Binding and Cleavage by the Human Mitochondrial Peptidase Neurolysin. Teixeira PF, et al. J Mol Biol, 2018 Feb 2. PMID 29183787
    4. Neuropeptide specificity and inhibition of recombinant isoforms of the endopeptidase 3.4.24.16 family: comparison with the related recombinant endopeptidase 3.4.24.15. Rioli V, et al. Biochem Biophys Res Commun, 1998 Sep 8. PMID 9735321
    5. The mitochondrial peptidase, neurolysin, regulates respiratory chain supercomplex formation and is necessary for AML viability. Mirali S, et al. Sci Transl Med, 2020 Apr 8. PMID 32269163

    See all (41) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Structural basis of divergent substrate recognition and inhibition of human neurolysin.
      Title: Structural basis of divergent substrate recognition and inhibition of human neurolysin.
    2. The mitochondrial peptidase, neurolysin, regulates respiratory chain supercomplex formation and is necessary for AML viability.
      Title: The mitochondrial peptidase, neurolysin, regulates respiratory chain supercomplex formation and is necessary for AML viability.
    3. The crystal structure of human neurolysin(E475Q) in complex with the products of neurotensin cleavage at 2.7A revealed a closed conformation with an internal cavity that restricts substrate length and highlighted the mechanism of enzyme opening/closing that is necessary for substrate binding and catalytic activity.
      Title: Mechanism of Peptide Binding and Cleavage by the Human Mitochondrial Peptidase Neurolysin.
    4. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
    5. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    6. Mutations at only two residues (Arg-470 and Arg-498) are required to swap specificity with thimet oligopeptidase, a result that is confirmed by testing the two-mutant constructs.
      Title: Swapping the substrate specificities of the neuropeptidases neurolysin and thimet oligopeptidase.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope transmembrane glycoprotein gp41 env A synthetic peptide corresponding to the immunosuppressive domain (amino acids 574-592) of HIV-1 gp41 downregulates the expression of neurolysin (NLN) in peptide-treated PBMCs PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ23002, KIAA1226, DKFZp564F123

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metalloendopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables metalloendopeptidase activity TAS
    Traceable Author Statement
    more info
    		  
    enables peptide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in G protein-coupled receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    involved_in peptide metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in proteolysis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of gluconeogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of skeletal muscle fiber differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in mitochondrial intermembrane space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion HTP PubMed 
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    neurolysin, mitochondrial
    Names
    angiotensin binding protein
    endopeptidase 24.16
    microsomal endopeptidase
    mitochondrial oligopeptidase M
    neurolysin (metallopeptidase M3 family)
    neurotensin endopeptidase
    NP_065777.1
    XP_005248616.1
    XP_047273399.1
    XP_047273400.1
    XP_047273401.1
    XP_054208976.1
    XP_054208977.1
    XP_054208978.1
    XP_054208979.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_020726.5 → NP_065777.1  neurolysin, mitochondrial

      See identical proteins and their annotated locations for NP_065777.1

      Status: REVIEWED

      Source sequence(s)
      AC016643, AJ300837, CA441264, CB992921
      Consensus CDS
      CCDS3989.1
      UniProtKB/Swiss-Prot
      Q9BYT8, Q9ULJ4
      UniProtKB/TrEMBL
      A8K9T8
      Related
      ENSP00000370372.5, ENST00000380985.10
      Conserved Domains (2) summary
      cd06455
      Location:58 → 699
      M3A_TOP; Peptidase M3 Thimet oligopeptidase (TOP) also includes neurolysin
      COG0339
      Location:54 → 701
      Dcp; Zn-dependent oligopeptidase [Posttranslational modification, protein turnover, chaperones]

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      65722205..65829283
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005248559.4 → XP_005248616.1  neurolysin, mitochondrial isoform X1

      See identical proteins and their annotated locations for XP_005248616.1

      UniProtKB/TrEMBL
      A8K9T8
      Conserved Domains (2) summary
      cd06455
      Location:58 → 681
      M3A_TOP; Peptidase M3 Thimet oligopeptidase (TOP) also includes neurolysin
      COG0339
      Location:54 → 683
      Dcp; Zn-dependent oligopeptidase [Posttranslational modification, protein turnover, chaperones]

    2. XM_047417445.1 → XP_047273401.1  neurolysin, mitochondrial isoform X3

    3. XM_047417444.1 → XP_047273400.1  neurolysin, mitochondrial isoform X2

    4. XM_047417443.1 → XP_047273399.1  neurolysin, mitochondrial isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      66543992..66651091
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054353001.1 → XP_054208976.1  neurolysin, mitochondrial isoform X1

    2. XM_054353004.1 → XP_054208979.1  neurolysin, mitochondrial isoform X3

    3. XM_054353003.1 → XP_054208978.1  neurolysin, mitochondrial isoform X2

    4. XM_054353002.1 → XP_054208977.1  neurolysin, mitochondrial isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9BYT8.1 GenPept UniProtKB/Swiss-Prot:Q9BYT8

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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