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Protein / target

Serine protease HTRA2, mitochondrial

Encoded byHTRA2O43464Homo sapiensSwiss-Prot
UniProt: O43464Ensembl: ENSG00000115317HGNC: HGNC:14348NCBI Gene: 27429
Antibody-tractable
Druggability
UniProt SigP or TMHMM
1
Research papers

Protein at a glance

Biological role

Protein serine/threonine kinase inhibitor

Strongest disease association

Neutropenia

Via encoding gene HTRA2 · Genetic literature evidence · score 0.76

Research activity

Emerging research

1 papers · latest 2025

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Serine protease that shows proteolytic activity against a non-specific substrate beta-casein.

View complete UniProt function annotation

Serine protease that shows proteolytic activity against a non-specific substrate beta-casein (PubMed:10873535). Promotes apoptosis by either relieving the inhibition of BIRC proteins on caspases, leading to an increase in caspase activity; or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism (PubMed:15200957). Cleaves BIRC6 and relieves its inhibition on CASP3, CASP7 and CASP9, but it is also prone to inhibition by BIRC6 (PubMed:36758104, PubMed:36758105). Cleaves THAP5 and promotes its degradation during apoptosis (PubMed:19502560)

Subcellular location

Mitochondrion intermembrane spaceMitochondrion membraneEndoplasmic reticulum
Domains and Gene Ontology detail (46)

Domains & features

PDZ

Gene Ontology

  • CCD40 receptor complex
  • Cchromatin
  • Ccytoplasmic side of plasma membrane
  • Ccytoskeleton
  • Ccytosol
  • Cendoplasmic reticulum
  • Cendoplasmic reticulum membrane
  • Cmembrane
  • Cmitochondrial intermembrane space
  • Cmitochondrial membrane
  • Cmitochondrion
  • Cnucleus

458 aa · 49 kDa · 4 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

ProteolysisUniProt · GOApoptosis & cell deathUniProt · GO
View supporting evidence

Proteolysis

  • ·Serine protease that shows proteolytic activity against a non-specific substrate beta-ca…
  • ·peptidase activity
  • ·serine-type endopeptidase activity
  • ·serine-type peptidase activity

Apoptosis & cell death

  • ·Serine protease that shows proteolytic activity against a non-specific substrate beta-ca…
  • ·negative regulation of neuron apoptotic process
  • ·neuron apoptotic process
  • ·positive regulation of apoptotic process

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene HTRA2

Gene-level evidence surfaced through the gene HTRA2 that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Neutropenia
0.61Moderately supported

Genetic literature evidence dominant · Open Targets 0.46

Genetic Diseases, Inborn
0.32Limited support

Genetic evidence dominant · Open Targets 0.19

Parkinson's Disease
0.29Preliminary

Animal model evidence dominant · Open Targets 0.12 · no direct causal or clinical evidence

Autistic Disorder
0.28Limited support

Genetic evidence dominant · Open Targets 0.12

Carcinoma, Ductal, Breast
0.12Preliminary

Somatic mutation evidence dominant · Open Targets 0.11

View evidence synthesis (5)
NeutropeniaModerately supported
0.61
agreement 0.46–0.76
Genetic literature98%Literature2%

Open Targets aggregate 0.46 · 2 independent evidence families

Genetic Diseases, InbornLimited support
0.32
agreement 0.18–0.46
Genetic99%Literature1%

Open Targets aggregate 0.19 · 2 independent evidence families

Parkinson's DiseasePreliminary
0.29
agreement 0.11–0.47
Animal model59%Literature41%

Open Targets aggregate 0.12 · 2 independent evidence families · no direct causal or clinical evidence

Autistic DisorderLimited support
0.28
agreement 0.16–0.41
Genetic59%Animal model41%

Open Targets aggregate 0.12 · 2 independent evidence families

Carcinoma, Ductal, BreastPreliminary
0.12
agreement 0.00–0.30
Somatic mutation100%

Open Targets aggregate 0.11 · 1 independent evidence family

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Neutropenia0.46
Genetic Diseases, Inborn0.19
Autistic Disorder0.12
Parkinson's Disease0.12
Carcinoma, Ductal, Breast0.11

Tractability

Antibodies — Emerging

Feasibility evidence (uniprot sigp or tmhmm) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (5)
AB · UniProt SigP or TMHMMPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2025

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Electrophysiology-based screening identifies neuronal HtrA serine peptidase 2 (HTRA2) as a synaptic plasticity regulator participating in tauopathy.7 cites

Zheng N · Translational psychiatry · 2025

Recent

Electrophysiology-based screening identifies neuronal HtrA serine peptidase 2 (HTRA2) as a synaptic plasticity regulator participating in tauopathy.

Zheng N · Translational psychiatry · 2025

Europe PMC papers linked directly to this protein.