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HTRA3 HtrA serine peptidase 3 [ Homo sapiens (human) ]

Gene ID: 94031, updated on 2-Nov-2024

Summary

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Official Symbol
HTRA3provided by HGNC
Official Full Name
HtrA serine peptidase 3provided by HGNC
Primary source
HGNC:HGNC:30406
See related
Ensembl:ENSG00000170801 MIM:608785; AllianceGenome:HGNC:30406
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
Prsp; Tasp
Summary
Enables endopeptidase activity; identical protein binding activity; and serine-type peptidase activity. Involved in proteolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Nov 2024]
Expression
Broad expression in ovary (RPKM 19.8), gall bladder (RPKM 16.9) and 19 other tissues See more
Orthologs
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Genomic context

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See HTRA3 in Genome Data Viewer
Location:
4p16.1
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (8269754..8307098)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (8248531..8287062)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (8271481..8308825)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8175771-8176270 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8177753-8178598 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8189546-8190072 Neighboring gene guanine monophosphate synthase pseudogene 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8191649-8192174 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:8193227-8193751 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21281 Neighboring gene SH3 domain and tetratricopeptide repeats 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21282 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21283 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15258 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21284 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21286 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21285 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21287 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21288 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8207619-8208120 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8208121-8208620 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8210744-8211508 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8217127-8217691 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8217692-8218255 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8228681-8229350 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21291 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8230692-8231362 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8239598-8240458 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8240459-8241317 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8243787-8244348 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8246371-8246872 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8253953-8254459 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8254460-8254965 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8261245-8261746 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15262 Neighboring gene uncharacterized LOC105374373 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8293385-8293884 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:8296956-8297199 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8297405-8297904 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8316207-8317036 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:8317037-8317864 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:8325636-8326136 Neighboring gene long intergenic non-protein coding RNA 2517 Neighboring gene uncharacterized LOC124900658

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues 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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Related articles in PubMed

  1. Hypoxia is involved in the reduction of HtrA3 in patients with endometrial hyperplasia and cancer. Lv Q, et al. Biochem Biophys Res Commun, 2018 Sep 18. PMID 30139517
  2. HtrA3 as an early marker for preeclampsia: specific monoclonal antibodies and sensitive high-throughput assays for serum screening. Dynon K, et al. PLoS One, 2012. PMID 23049902, Free PMC Article
  3. HTRA3 is reduced in ovarian cancers regardless of stage. Zhao M, et al. Cancer Invest, 2014 Nov. PMID 25274382
  4. The high-temperature requirement factor A3 (HtrA3) is associated with acquisition of the invasive phenotype in oral squamous cell carcinoma cells. Moriya Y, et al. Oral Oncol, 2015 Jan. PMID 25456008
  5. HtrA3: a promising prognostic biomarker and therapeutic target for head and neck squamous cell carcinoma. Chen Y, et al. PeerJ, 2023. PMID 37842043, Free PMC Article

See all (57) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. HtrA3: a promising prognostic biomarker and therapeutic target for head and neck squamous cell carcinoma.
    Title: HtrA3: a promising prognostic biomarker and therapeutic target for head and neck squamous cell carcinoma.
  2. A Pan-Cancer Analysis to Provide Insight into the Immunological Role and Prognostic Value of HTRA3.
    Title: A Pan-Cancer Analysis to Provide Insight into the Immunological Role and Prognostic Value of HTRA3.
  3. mmu-lncRNA 121686/hsa-lncRNA 520657 induced by METTL3 drive the progression of AKI by targeting miR-328-5p/HtrA3 signaling axis.
    Title: mmu-lncRNA 121686/hsa-lncRNA 520657 induced by METTL3 drive the progression of AKI by targeting miR-328-5p/HtrA3 signaling axis.
  4. Study on the Correlation between the Levels of HtrA3 and TGF-beta2 in Late Pregnancy and Preeclampsia.
    Title: Study on the Correlation between the Levels of HtrA3 and TGF-β2 in Late Pregnancy and Preeclampsia.
  5. Hsa-miR-494-3p attenuates gene HtrA3 transcription to increase inflammatory response in hypoxia/reoxygenation HK2 Cells.
    Title: Hsa-miR-494-3p attenuates gene HtrA3 transcription to increase inflammatory response in hypoxia/reoxygenation HK2 Cells.
  6. 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.
  7. Our study also reports an intricate ligand-induced allosteric switch, which redefines the existing hypothesis of HtrA3 activation besides opening up avenues for modulating protease activity favorably through suitable effector molecules.
    Title: A distinct concerted mechanism of structural dynamism defines activity of human serine protease HtrA3.
  8. HtrA3 isoforms stimulate drug-induced apoptotic death of lung cancer cells via XIAP cleavage.
    Title: The HtrA3 protease promotes drug-induced death of lung cancer cells by cleavage of the X-linked inhibitor of apoptosis protein (XIAP).
  9. This study reports allosteric modulation of Human HtrA3 (High temperature requirement protease A3) enzyme activity for the first time. A novel non-classical allosteric ligand binding pocket mediates allostery in HtrA3.
    Title: Identification of a distal allosteric ligand binding pocket in HtrA3.
  10. Low expression of HtrA3 at 15 weeks is associated with, and may be useful for, the early detection of late-onset preeclampsia development and small for gestational age birth.
    Title: Low Serum Levels of HtrA3 at 15 Weeks of Gestation Are Associated with Late-Onset Preeclampsia Development and Small for Gestational Age Birth.
Submit: New GeneRIF Correction See all GeneRIFs (43)

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

Variation

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See Variation Viewer (GRCh37.p13)

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables endopeptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
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 peptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in negative regulation of BMP signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of transforming growth factor beta receptor signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in proteolysis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in extracellular region IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
serine protease HTRA3
Names
high-temperature requirement factor A3
pregnancy-related serine protease
probable serine protease HTRA3

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.

mRNA and Protein(s)

  1. NM_001297559.3 → NP_001284488.1  serine protease HTRA3 isoform 2 precursor

    See identical proteins and their annotated locations for NP_001284488.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) lacks several exons, and contains an alternate 3'-terminal exon, compared to variant 1. The encoded isoform (2) has a shorter and distinct C-terminus.
    Source sequence(s)
    AC113611, AW072765, AY280666, DN996853
    Consensus CDS
    CCDS75105.1
    UniProtKB/Swiss-Prot
    P83110
    Related
    ENSP00000371952.3, ENST00000382512.3
    Conserved Domains (3) summary
    pfam00219
    Location:25 → 76
    IGFBP; Insulin-like growth factor binding protein
    pfam07648
    Location:81 → 126
    Kazal_2; Kazal-type serine protease inhibitor domain
    pfam13365
    Location:175 → 319
    Trypsin_2; Trypsin-like peptidase domain

  2. NM_053044.5 → NP_444272.1  serine protease HTRA3 isoform 1 precursor

    See identical proteins and their annotated locations for NP_444272.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC113611, BC035717
    Consensus CDS
    CCDS3400.1
    UniProtKB/Swiss-Prot
    P83110, Q7Z7A2
    Related
    ENSP00000303766.2, ENST00000307358.7
    Conserved Domains (4) summary
    cd00987
    Location:355 → 440
    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 ...
    pfam00219
    Location:25 → 76
    IGFBP; Insulin-like growth factor binding protein
    pfam07648
    Location:81 → 126
    Kazal_2; Kazal-type serine protease inhibitor domain
    pfam13365
    Location:175 → 319
    Trypsin_2; Trypsin-like peptidase domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

    Range
    8269754..8307098
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011513596.4 → XP_011511898.1  serine protease HTRA3 isoform X1

    Conserved Domains (3) summary
    pfam00219
    Location:25 → 76
    IGFBP; Insulin-like growth factor binding protein
    pfam07648
    Location:81 → 126
    Kazal_2; Kazal-type serine protease inhibitor domain
    pfam13365
    Location:175 → 319
    Trypsin_2; Trypsin-like peptidase domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    8248531..8287062
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054351282.1 → XP_054207257.1  serine protease HTRA3 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P83110.2 GenPept UniProtKB/Swiss-Prot:P83110

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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