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Nep4 Neprilysin 4 [ Drosophila melanogaster (fruit fly) ]

Gene ID: 42449, updated on 3-Jun-2026
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; pericardial cell; and somatic muscle cell. Used to study heart conduction disease. Human ortholog(s) of this gene implicated in Charcot-Marie-Tooth disease axonal type 2T; X-linked 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, Jul 2025]
Orthologs
all
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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

Go to nucleotide: Graphics FASTA GenBank

Related articles in PubMed

  1. Neprilysin 4 controls acrosome structure and male fertility in Drosophila melanogaster. Buhr A, et al. Commun Biol, 2025 Nov 22. PMID 41274942, Free PMC Article
  2. Neprilysin 4: an essential peptidase with multifaceted physiological relevance. Buhr A, et al. Biol Chem, 2023 Apr 25. PMID 36653344
  3. 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
  4. 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
  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 (47) 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
Products Interactant Other Gene Complex Source Pubs Description

Homology

Gene Ontology Provided by FlyBase

Function Evidence Code Pubs
enables endopeptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables metalloendopeptidase activity EXP
Inferred from Experiment
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 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 cytoplasm EXP
Inferred from Experiment
more info
 PubMed 
located_in cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in extracellular region IDA
Inferred from Direct Assay
more info
 PubMed 
located_in membrane ISM
Inferred from Sequence Model
more info
 PubMed 
located_in plasma membrane EXP
Inferred from Experiment
more info
 PubMed 
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in sarcoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
located_in sarcoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
  
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

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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

    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

    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

    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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