HTRA2 HtrA serine peptidase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HTRA2provided by HGNC
Official Full Name: HtrA serine peptidase 2provided by HGNC
Primary source: HGNC:HGNC:14348
See related: Ensembl:ENSG00000115317 MIM:606441; AllianceGenome:HGNC:14348
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: OMI; MGCA8; PARK13; PRSS25
Summary: 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]
Expression: Ubiquitous expression in spleen (RPKM 12.3), bone marrow (RPKM 11.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2p13.1

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (74529405..74533556)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (74537971..74542122)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (74756532..74760683)

Chromosome 2 - NC_000002.12 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

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Cytosolic retention of HtrA2 during mitochondrial protein import stress triggers the DELE1-HRI pathway.
Title: Cytosolic retention of HtrA2 during mitochondrial protein import stress triggers the DELE1-HRI pathway.
HTRA2/OMI-Mediated Mitochondrial Quality Control Alters Macrophage Polarization Affecting Systemic Chronic Inflammation.
Title: HTRA2/OMI-Mediated Mitochondrial Quality Control Alters Macrophage Polarization Affecting Systemic Chronic Inflammation.
Role of high-temperature requirement serine protease A 2 in rheumatoid inflammation.
Title: Role of high-temperature requirement serine protease A 2 in rheumatoid inflammation.
HtrA2 regulates alpha-Synuclein-mediated mitochondrial reactive oxygen species production in the mitochondria of microglia.
Title: HtrA2 regulates α-Synuclein-mediated mitochondrial reactive oxygen species production in the mitochondria of microglia.
A new function for the serine protease HtrA2 in controlling radiation-induced senescence in cancer cells.
Title: A new function for the serine protease HtrA2 in controlling radiation-induced senescence in cancer cells.
Role of conserved regulatory loop residues in allosteric propagation of serine protease HtrA2.
Title: Role of conserved regulatory loop residues in allosteric propagation of serine protease HtrA2.
Loss of high-temperature requirement protein A2 protease activity induces mitonuclear imbalance via differential regulation of mitochondrial biogenesis in sarcopenia.
Title: Loss of high-temperature requirement protein A2 protease activity induces mitonuclear imbalance via differential regulation of mitochondrial biogenesis in sarcopenia.
Association study of DNAJC13, UCHL1, HTRA2, GIGYF2, and EIF4G1 with Parkinson's disease.
Title: Association study of DNAJC13, UCHL1, HTRA2, GIGYF2, and EIF4G1 with Parkinson's disease.
Expression of HTRA Genes and Its Association with Microsatellite Instability and Survival of Patients with Colorectal Cancer.
Title: Expression of HTRA Genes and Its Association with Microsatellite Instability and Survival of Patients with Colorectal Cancer.
Intrafamilial ""DOA-plus"" phenotype variability related to different OMI/HTRA2 expression.
Title: Intrafamilial "DOA-plus" phenotype variability related to different OMI/HTRA2 expression.

Submit: New GeneRIF Correction See all GeneRIFs (111)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
3-methylglutaconic aciduria type 8 MedGen: C4310650 OMIM: 617248 GeneReviews: Not available	Compare labs
Parkinson disease 13, autosomal dominant, susceptibility to MedGen: C1853202 OMIM: 610297 GeneReviews: Parkinson Disease Overview	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

MARC_5801-5802:991939731:1 (e-PCR)
- UniSTS:231172

MARC_5801-5802:997299306:1 (e-PCR)
- UniSTS:231172

BCD2341 (e-PCR)
- UniSTS:82012

RH15974 (e-PCR)
- UniSTS:3969

A006U29 (e-PCR)
- UniSTS:16002

D2S1958E (e-PCR)
- UniSTS:153730

D2S1577E (e-PCR)
- UniSTS:150661

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables peptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction 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	IMP Inferred from Mutant Phenotype more info	PubMed
enables serine-type endopeptidase activity	TAS Traceable Author Statement more info	PubMed
enables serine-type peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables serine-type peptidase activity	TAS Traceable Author Statement more info	PubMed
enables unfolded protein binding	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in adult walking behavior	IEA Inferred from Electronic Annotation more info
involved_in cellular response to growth factor stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to heat	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to interferon-beta	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to oxidative stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to oxidative stress	NAS Non-traceable Author Statement more info	PubMed
involved_in cellular response to retinoic acid	IDA Inferred from Direct Assay more info	PubMed
involved_in ceramide metabolic process	IEA Inferred from Electronic Annotation more info
involved_in execution phase of apoptosis	TAS Traceable Author Statement more info	PubMed
involved_in forebrain development	IEA Inferred from Electronic Annotation more info
involved_in intrinsic apoptotic signaling pathway in response to DNA damage	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrial protein catabolic process	TAS Traceable Author Statement more info
involved_in negative regulation of cell cycle	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of mitophagy in response to mitochondrial depolarization	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of neuron apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in neuron development	IEA Inferred from Electronic Annotation more info
involved_in pentacyclic triterpenoid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of execution phase of apoptosis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein targeting to mitochondrion	HMP more info	PubMed
involved_in programmed cell death	IBA Inferred from Biological aspect of Ancestor more info
involved_in programmed cell death	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autoprocessing	TAS Traceable Author Statement more info	PubMed
involved_in protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteolysis	TAS Traceable Author Statement more info	PubMed
involved_in regulation of autophagy of mitochondrion	TAS Traceable Author Statement more info	PubMed
involved_in regulation of multicellular organism growth	IEA Inferred from Electronic Annotation more info
involved_in response to herbicide	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of CD40 receptor complex	ISS Inferred from Sequence or Structural Similarity more info
part_of chromatin	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic side of plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	NAS Non-traceable Author Statement more info	PubMed
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info	PubMed
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial intermembrane space	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial intermembrane space	TAS Traceable Author Statement more info
located_in mitochondrial membrane	IEA Inferred from Electronic Annotation more info
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	IMP Inferred from Mutant Phenotype more info	PubMed
located_in mitochondrion	TAS Traceable Author Statement more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of serine-type endopeptidase complex	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: serine protease HTRA2, mitochondrial

Names: HtrA-like serine protease; Omi stress-regulated endoprotease; epididymis secretory sperm binding protein; high temperature requirement protein A2; protease, serine, 25; serine protease 25; serine proteinase OMI

NP_001308656.1

EC 3.4.21.108

NP_001308657.1

EC 3.4.21.108

NP_037379.1

EC 3.4.21.108

NP_659540.1

EC 3.4.21.108

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012163.1 RefSeqGene

Range

5529..8915

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001321727.1 → NP_001308656.1 serine protease HTRA2, mitochondrial isoform 3 preproprotein

Status: REVIEWED

Source sequence(s)

AC005041

Consensus CDS

CCDS92785.1

UniProtKB/TrEMBL

A0A0C4DG44

Related

ENSP00000399166.2, ENST00000437202.2

Conserved Domains (2) summary

cd00989
Location:382 → 432

PDZ_metalloprotease; PDZ domain of bacterial and plant zinc metalloprotases, presumably membrane-associated or integral membrane proteases, which may be involved in signalling and regulatory mechanisms. May be responsible for substrate recognition and/or binding, as most PDZ ...

pfam13365
Location:182 → 330

Trypsin_2; Trypsin-like peptidase domain
NM_001321728.1 → NP_001308657.1 serine protease HTRA2, mitochondrial isoform 4 preproprotein

Status: REVIEWED

Source sequence(s)

AC005041

Consensus CDS

CCDS92786.1

UniProtKB/TrEMBL

A0A0C4DG44, A0A8Q3SIX7

Related

ENSP00000512836.1, ENST00000696727.1

Conserved Domains (2) summary

cd00989
Location:372 → 422

PDZ_metalloprotease; PDZ domain of bacterial and plant zinc metalloprotases, presumably membrane-associated or integral membrane proteases, which may be involved in signalling and regulatory mechanisms. May be responsible for substrate recognition and/or binding, as most PDZ ...

pfam13365
Location:182 → 320

Trypsin_2; Trypsin-like peptidase domain
NM_013247.5 → NP_037379.1 serine protease HTRA2, mitochondrial isoform 1 preproprotein

See identical proteins and their annotated locations for NP_037379.1

Status: REVIEWED

Source sequence(s)

AF141305, BF939362

Consensus CDS

CCDS1951.1

UniProtKB/Swiss-Prot

O43464, Q9HBZ4, Q9P0Y3, Q9P0Y4

UniProtKB/TrEMBL

A0A384MDW9, A8K7G2

Related

ENSP00000258080.3, ENST00000258080.8

Conserved Domains (1) summary

cl28339
Location:150 → 453

DegQ; Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones]
NM_145074.2 → NP_659540.1 serine protease HTRA2, mitochondrial isoform 2 preproprotein

See identical proteins and their annotated locations for NP_659540.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks two in-frame exons in the coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1 and has a modified PDZ domain. Isoform 2 has no detectable protease activity.

Source sequence(s)

AF141305, AF184911, BF939362

Consensus CDS

CCDS1952.1

UniProtKB/TrEMBL

A0A0C4DG44

Related

ENSP00000312893.3, ENST00000352222.7

Conserved Domains (2) summary

cd00989
Location:307 → 357

PDZ_metalloprotease; PDZ domain of bacterial and plant zinc metalloprotases, presumably membrane-associated or integral membrane proteases, which may be involved in signalling and regulatory mechanisms. May be responsible for substrate recognition and/or binding, as most PDZ ...

pfam13365
Location:182 → 255

Trypsin_2; Trypsin-like peptidase domain