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    Nep4 Neprilysin 4 [ Drosophila melanogaster (fruit fly) ]

    Gene ID: 42449, updated on 9-Dec-2024

    Summary

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    Official Symbol
    Nep4provided by FlyBase
    Official Full Name
    Neprilysin 4provided by FlyBase
    Primary source
    FLYBASE:FBgn0038818
    Locus tag
    Dmel_CG4058
    See related
    AllianceGenome:FB:FBgn0038818
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Drosophila melanogaster
    Lineage
    Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora
    Also known as
    CG4058; Dmel\CG4058; DmeNEP4; dNEP4; nep4; NEP4; Nep4A; nep4B
    Summary
    Enables endopeptidase activity. Involved in proteolysis. Located in extracellular space and sarcoplasmic reticulum. Is expressed in several structures, including brain; glial cell; male germline cell; somatic muscle cell; and visceral mesoderm derivative. Used to study heart conduction disease. Human ortholog(s) of this gene implicated in Charcot-Marie-Tooth disease axonal type 2T; X-linked dominant hypophosphatemic rickets; cerebral amyloid angiopathy; membranous glomerulonephritis; and neurodegenerative disease (multiple). Orthologous to several human genes including MME (membrane metalloendopeptidase) and MMEL1 (membrane metalloendopeptidase like 1). [provided by Alliance of Genome Resources, Dec 2024]
    Orthologs
    all
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    Genomic context

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    See Nep4 in Genome Data Viewer
    Location:
    92F4-92F5; 3-69 cM
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    Release 6.54 current Release 6 plus ISO1 MT (GCF_000001215.4) 3R NT_033777.3 (20652567..20659904, complement)
    Release 5.57 previous assembly Release 5 (GCF_000001215.2) 3R NT_033777.2 (16478289..16485626, complement)

    Chromosome 3R - NT_033777.3Genomic Context describing neighboring genes Neighboring gene Leucine-rich repeat kinase Neighboring gene Glutamate receptor IIE Neighboring gene Glutamate receptor IID Neighboring gene Cuticular protein 92F Neighboring gene antisense RNA:CR45024 Neighboring gene uncharacterized protein

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Neprilysin 4: an essential peptidase with multifaceted physiological relevance. Buhr A, et al. Biol Chem, 2023 Apr 25. PMID 36653344
    2. Neprilysins regulate muscle contraction and heart function via cleavage of SERCA-inhibitory micropeptides. Schiemann R, et al. Nat Commun, 2022 Jul 29. PMID 35906206, Free PMC Article
    3. Drosophila Neprilysins Are Involved in Middle-Term and Long-Term Memory. Turrel O, et al. J Neurosci, 2016 Sep 14. PMID 27629706, Free PMC Article
    4. The neprilysin (NEP) family of zinc metalloendopeptidases: genomics and function. Turner AJ, et al. Bioessays, 2001 Mar. PMID 11223883
    5. Toxicities of amyloid-beta and tau protein are reciprocally enhanced in the Drosophila model. Sun ZD, et al. Neural Regen Res, 2022 Oct. PMID 35259851, Free PMC Article

    See all (46) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Neprilysin 4: an essential peptidase with multifaceted physiological relevance.
      Title: Neprilysin 4: an essential peptidase with multifaceted physiological relevance.
    2. The Drosophila Neprilysin 4 gene is essential for sperm function following sperm transfer to females.
      Title: The Drosophila Neprilysin 4 gene is essential for sperm function following sperm transfer to females.
    3. Herein, the authors show that in Drosophila expression of insulin-like peptides is regulated by neprilysin 4 activity.
      Title: Drosophila neprilysins control insulin signaling and food intake via cleavage of regulatory peptides.
    4. The NEP4 involved in middle-term memory (MTM) and long-term memory (LTM) and that their expression is required in the mushroom bodies and also in a single pair of closely connected neurons.
      Title: Drosophila Neprilysins Are Involved in Middle-Term and Long-Term Memory.
    5. Overexpression of Nep4 leads to a severe muscle degeneration.
      Title: A novel role for the non-catalytic intracellular domain of Neprilysins in muscle physiology.
    6. Results report the identification and first characterization of neprilysin 4 (NEP4) from Drosophila melanogaster.
      Title: Neprilysin 4, a novel endopeptidase from Drosophila melanogaster, displays distinct substrate specificities and exceptional solubility states.
    Submit: New GeneRIF Correction

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Homology

    Gene Ontology Provided by FlyBase

    Function Evidence Code Pubs
    enables endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables metalloendopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables metalloendopeptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metallopeptidase activity ISM
    Inferred from Sequence Model
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in protein processing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in proteolysis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in proteolysis ISM
    Inferred from Sequence Model
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane ISM
    Inferred from Sequence Model
    more info
    		 PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in sarcoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    neprilysin 4
    Names
    CG4058-PA
    CG4058-PB
    CG4058-PC
    Nep4-PA
    Nep4-PB
    Nep4-PC
    neprilysin4
    NP_001262773.1
    NP_650904.3
    NP_732540.2

    NCBI Reference Sequences (RefSeq)

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    Genome Annotation

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

    Reference assembly

    Genomic

    1. NT_033777.3 Reference assembly

      Range
      20652567..20659904 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001275844.1 → NP_001262773.1  neprilysin 4, isoform C [Drosophila melanogaster]

      See identical proteins and their annotated locations for NP_001262773.1

      Status: REVIEWED

      UniProtKB/Swiss-Prot
      Q8T062
      Conserved Domains (2) summary
      cd08662
      Location:212 → 976
      M13; Peptidase family M13 includes neprilysin, endothelin-converting enzyme I
      COG3590
      Location:207 → 978
      PepO; Predicted metalloendopeptidase [Posttranslational modification, protein turnover, chaperones]

    2. NM_169912.1 → NP_732540.2  neprilysin 4, isoform B [Drosophila melanogaster]

      See identical proteins and their annotated locations for NP_732540.2

      Status: REVIEWED

      UniProtKB/Swiss-Prot
      Q8T062
      Related
      FBpp0083344, FBtr0083936
      Conserved Domains (2) summary
      cd08662
      Location:212 → 976
      M13; Peptidase family M13 includes neprilysin, endothelin-converting enzyme I
      COG3590
      Location:207 → 978
      PepO; Predicted metalloendopeptidase [Posttranslational modification, protein turnover, chaperones]

    3. NM_142647.3 → NP_650904.3  neprilysin 4, isoform A [Drosophila melanogaster]

      See identical proteins and their annotated locations for NP_650904.3

      Status: REVIEWED

      UniProtKB/Swiss-Prot
      Q8T062, Q9I7I4
      Related
      FBpp0083345
      Conserved Domains (1) summary
      cd08662
      Location:274 → 1038
      M13; Peptidase family M13 includes neprilysin, endothelin-converting enzyme I
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8T062.1 Q8T062

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