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    HtrA2 HTRA2-related serine protease [ Drosophila melanogaster (fruit fly) ]

    Gene ID: 41756, updated on 27-Dec-2024

    Summary

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    Official Symbol
    HtrA2provided by FlyBase
    Official Full Name
    HTRA2-related serine proteaseprovided by FlyBase
    Primary source
    FLYBASE:FBgn0038233
    Locus tag
    Dmel_CG8464
    See related
    AllianceGenome:FB:FBgn0038233
    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
    CG8464; Dmel\CG8464; Dmel_CG8464; DmHtrA2; domi; dOmi; htrA2; HTRA2; htrA2/omi; HtrA2/Omi; omi; Omi; Omi/HtrA2
    Summary
    Enables serine-type endopeptidase activity. Involved in several processes, including ectopic germ cell programmed cell death; mitochondrion organization; and spermatogenesis. Located in Nebenkern; cytosol; and mitochondrial intermembrane space. Is expressed in adult head and organism. Used to study Parkinson's disease. Human ortholog(s) of this gene implicated in several diseases, including 3-methylglutaconic aciduria type 8; CADASIL (multiple); gastrointestinal system cancer (multiple); macular degeneration (multiple); and neurodegenerative disease (multiple). Orthologous to several human genes including HTRA2 (HtrA serine peptidase 2). [provided by Alliance of Genome Resources, Dec 2024]
    Orthologs
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    Genomic context

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    See HtrA2 in Genome Data Viewer
    Location:
    88C3-88C3; 3-55 cM
    Exon count:
    3
    Annotation release Status Assembly Chr Location
    Release 6.54 current Release 6 plus ISO1 MT (GCF_000001215.4) 3R NT_033777.3 (14509049..14511712, complement)
    Release 5.57 previous assembly Release 5 (GCF_000001215.2) 3R NT_033777.2 (10334771..10337434, complement)

    Chromosome 3R - NT_033777.3Genomic Context describing neighboring genes Neighboring gene crossveinless c Neighboring gene antisense RNA:CR44176 Neighboring gene natalisin Neighboring gene long non-coding RNA:CR44177 Neighboring gene mitochondrial ribosomal protein L11 Neighboring gene uncharacterized protein Neighboring gene uncharacterized protein Neighboring gene Phosphodiesterase 6

    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. Neuroprotective function of Omi to α-synuclein-induced neurotoxicity. Chung HJ, et al. Neurobiol Dis, 2020 Mar. PMID 31837423
    2. The HtrA2 Drosophila model of Parkinson's disease is suppressed by the pro-survival Bcl-2 Buffy. M'Angale PG, et al. Genome, 2017 Jan. PMID 27848260
    3. A conserved function for pericentromeric satellite DNA. Jagannathan M, et al. Elife, 2018 Mar 26. PMID 29578410, Free PMC Article
    4. Evolution of mitochondrial cell death pathway: Proapoptotic role of HtrA2/Omi in Drosophila. Igaki T, et al. Biochem Biophys Res Commun, 2007 May 18. PMID 17397804
    5. Rhomboid-7 and HtrA2/Omi act in a common pathway with the Parkinson's disease factors Pink1 and Parkin. Whitworth AJ, et al. Dis Model Mech, 2008 Sep-Oct. PMID 19048081, Free PMC Article

    See all (72) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Neuroprotective function of Omi to alpha-synuclein-induced neurotoxicity.
      Title: Neuroprotective function of Omi to α-synuclein-induced neurotoxicity.
    2. Mitochondrial serine protease HtrA2/Omi is an important mediator of germ cell death.
      Title: Alternative germ cell death pathway in Drosophila involves HtrA2/Omi, lysosomes, and a caspase-9 counterpart.
    3. Data show the presence of apoptosis at the cellular level in both ade2 and Prat mutants, and the upregulated gene HtrA2, which encodes an apoptosis effector and is thus a candidate for initiating apoptosis in response to purine depletion.
      Title: A link between impaired purine nucleotide synthesis and apoptosis in Drosophila melanogaster.
    4. HtrA2 was shown to be phosphorylated in a PINK1-dependent manner, suggesting it might act in the PINK1 pathway.
      Title: Drosophila HtrA2 is dispensable for apoptosis but acts downstream of PINK1 independently from Parkin.
    5. found that Rhomboid-7, a mitochondrial protease not previously implicated in PD, acts as an upstream component of this pathway, and showed that it is required to cleave the precursor forms of both Pink1 and Omi
      Title: Rhomboid-7 and HtrA2/Omi act in a common pathway with the Parkinson's disease factors Pink1 and Parkin.
    6. The binding of DIAP1 to dOmi resulted in DIAP1-mediated polyubiquitination of dOmi, suggesting that DIAP1 could target dOmi for proteasomal degradation.
      Title: The interaction of DIAP1 with dOmi/HtrA2 regulates cell death in Drosophila.
    7. Drosophila Omi (dOmi), a fly homologue of the serine protease Omi/HtrA2, alleviates th/DIAP1 inhibition of all caspases by proteolytically degrading th/DIAP1 and induces apoptosis both in cultured cells and in the developing fly eye.
      Title: Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease.
    Submit: New GeneRIF Correction

    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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    Homology

    Gene Ontology Provided by FlyBase

    Function Evidence Code Pubs
    enables peptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables serine hydrolase activity HDA PubMed 
    enables serine-type endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables serine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables serine-type endopeptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables serine-type endopeptidase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in ectopic germ cell programmed cell death IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitochondrion organization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of apoptotic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in programmed cell death IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in proteolysis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in spermatogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in Nebenkern IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial intermembrane space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    HTRA2-related serine protease
    Names
    CG8464-PA
    CG8464-PB
    HtrA2-PA
    HtrA2-PB
    high temperature requirement A2
    serine protease HTRA2
    NP_001262565.1
    NP_650366.1

    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
      14509049..14511712 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001275636.1 → NP_001262565.1  HTRA2-related serine protease, isoform B [Drosophila melanogaster]

      See identical proteins and their annotated locations for NP_001262565.1

      Status: REVIEWED

      UniProtKB/Swiss-Prot
      Q9VFJ3
      UniProtKB/TrEMBL
      A0A0B4KG52
      Conserved Domains (3) summary
      COG0265
      Location:67 → 422
      DegQ; Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones]
      cd00987
      Location:323 → 417
      PDZ_serine_protease; PDZ domain of trypsin-like serine proteases, such as DegP/HtrA, which are oligomeric proteins involved in heat-shock response, chaperone function, and apoptosis. May be responsible for substrate recognition and/or binding, as most PDZ domains bind ...
      pfam13365
      Location:141 → 280
      Trypsin_2; Trypsin-like peptidase domain

    2. NM_142109.2 → NP_650366.1  HTRA2-related serine protease, isoform A [Drosophila melanogaster]

      See identical proteins and their annotated locations for NP_650366.1

      Status: REVIEWED

      UniProtKB/Swiss-Prot
      Q9VFJ3
      UniProtKB/TrEMBL
      A0A0B4KG52
      Related
      FBpp0082446
      Conserved Domains (3) summary
      COG0265
      Location:67 → 422
      DegQ; Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones]
      cd00987
      Location:323 → 417
      PDZ_serine_protease; PDZ domain of trypsin-like serine proteases, such as DegP/HtrA, which are oligomeric proteins involved in heat-shock response, chaperone function, and apoptosis. May be responsible for substrate recognition and/or binding, as most PDZ domains bind ...
      pfam13365
      Location:141 → 280
      Trypsin_2; Trypsin-like peptidase domain
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    A0A0B4KG52 A0A0B4KG52
    Q9VFJ3.1 Q9VFJ3

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