Seroatlas · Human Serome Atlas

HTRA2

Serine protease HTRA2, mitochondrial

Also known as: HTRA2_HUMAN, OMI, PARK13, PRSS25

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
O43464
Gene
HTRA2
Ensembl
ENSG00000115317
Chromosome
2
Canonical length
458 aa
Protein class
Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted membrane proteins
Subcellular location
Mitochondria
Quaternary structure
Homotrimer

OverviewNCBI Gene

This gene encodes a serine protease. The protein has been localized in the endoplasmic reticulum and interacts with an alternatively spliced form of mitogen-activated protein kinase 14. The protein has also been localized to the mitochondria with release to the cytosol following apoptotic stimulus. The protein is thought to induce apoptosis by binding the apoptosis inhibitory protein baculoviral IAP repeat-containing 4. Nuclear localization of this protein has also been observed. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

Canonical amino-acid sequenceUniProt

458 residues, UniProt reviewed canonical sequence.

>O43464|HTRA2
     1  MAAPRAGRGA GWSLRAWRAL GGIRWGRRPR LTPDLRALLT SGTSDPRARV TYGTPSLWAR
    61  LSVGVTEPRA CLTSGTPGPR AQLTAVTPDT RTREASENSG TRSRAWLAVA LGAGGAVLLL
   121  LWGGGRGPPA VLAAVPSPPP ASPRSQYNFI ADVVEKTAPA VVYIEILDRH PFLGREVPIS
   181  NGSGFVVAAD GLIVTNAHVV ADRRRVRVRL LSGDTYEAVV TAVDPVADIA TLRIQTKEPL
   241  PTLPLGRSAD VRQGEFVVAM GSPFALQNTI TSGIVSSAQR PARDLGLPQT NVEYIQTDAA
   301  IDFGNSGGPL VNLDGEVIGV NTMKVTAGIS FAIPSDRLRE FLHRGEKKNS SSGISGSQRR
   361  YIGVMMLTLS PSILAELQLR EPSFPDVQHG VLIHKVILGS PAHRAGLRPG DVILAIGEQM
   421  VQNAEDVYEA VRTQSQLAVQ IRRGRETLTL YVTPEVTE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HTRA2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Other membrane
Secreted
No
Transmembrane segments
1
Mean surface accessibility (rSASA)
0.41
Highest tissue expression
15 nTPM

Expression across tissuesHPA

Tissue

  • ovary: 15 nTPM
  • spleen: 14 nTPM
  • skeletal muscle: 14 nTPM
  • blood vessel: 14 nTPM
  • adipose tissue: 13 nTPM
  • bone marrow: 12 nTPM

Single-cell type

  • megakaryocytes: 111 nCPM
  • early primary spermatocytes: 69 nCPM
  • late spermatids: 68 nCPM
  • erythrocyte progenitors: 65 nCPM
  • megakaryocyte progenitors: 57 nCPM
  • platelets: 51 nCPM

Immune cell

  • memory B-cell: 10 nTPM
  • naive B-cell: 9.5 nTPM
  • myeloid DC: 8.6 nTPM
  • classical monocyte: 7.3 nTPM
  • basophil: 5.7 nTPM
  • intermediate monocyte: 5.7 nTPM

Brain region

  • thalamus: 17 nTPM
  • cerebellum: 16 nTPM
  • white matter: 15 nTPM
  • basal ganglia: 14 nTPM
  • medulla oblongata: 14 nTPM
  • midbrain: 14 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HTRA2.

Disease | AllUniProt

Conditions HTRA2 is implicated in, by any mechanism.

Disease | GeneticClinVar

17 pathogenic / likely-pathogenic of 365 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • 3-methylglutaconic aciduria type 8
  • HTRA2-Related Disorders
  • Parkinson disease 13, autosomal dominant, susceptibility to

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.76
gnomAD pLI
0
gnomAD missense Z
1.7
DepMap mean gene effect
-0.07
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of HTRA2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads HTRA2 as an antibody target. Whether an autoantibody or antibody against HTRA2 could matter depends on whether native HTRA2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

HTRA2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label HTRA2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/HTRA2. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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