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

Summary

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; positive regulation of apoptotic process; 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: all
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Genomic context

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_033777.3 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Neuroprotective function of Omi to alpha-synuclein-induced neurotoxicity.
Title: Neuroprotective function of Omi to α-synuclein-induced neurotoxicity.
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.
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.
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.
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.
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.
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.

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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

NCBI Orthologs

Orthologs from OrthoDB

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 more info	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

EC 3.4.-.-

EC 3.4.21.-

EC 3.4.24.-

NP_650366.1

EC 3.4.-.-

EC 3.4.21.-

EC 3.4.24.-

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

NT_033777.3 Reference assembly

Range

14509049..14511712 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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