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HTRA4 HtrA serine peptidase 4 [ Homo sapiens (human) ]

Gene ID: 203100, updated on 2-Nov-2024

Summary

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Official Symbol
HTRA4provided by HGNC
Official Full Name
HtrA serine peptidase 4provided by HGNC
Primary source
HGNC:HGNC:26909
See related
Ensembl:ENSG00000169495 MIM:610700; AllianceGenome:HGNC:26909
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
Summary
This gene encodes a member of the HtrA family of proteases. The encoded protein contains a putative signal peptide, an insulin growth factor binding domain, a Kazal protease inhibitor domain, a conserved trypsin domain and a PDZ domain. Based on studies on other related family members, this enzyme may function as a secreted oligomeric chaperone protease to degrade misfolded secretory proteins. Other human HtrA proteins have been implicated in arthritis, tumor suppression, unfolded stress response, apoptosis, and aging. [provided by RefSeq, Oct 2008]
Expression
Biased expression in placenta (RPKM 16.9) and bone marrow (RPKM 1.2) See more
Orthologs
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Genomic context

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See HTRA4 in Genome Data Viewer
Location:
8p11.22
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (38974228..38988663)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (39251369..39265805)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (38831747..38846182)

Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:38591927-38592426 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:38593007-38593506 Neighboring gene Sharpr-MPRA regulatory region 10821 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19133 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19134 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19135 Neighboring gene transforming acidic coiled-coil containing protein 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27257 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27258 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19136 Neighboring gene Sharpr-MPRA regulatory region 13542 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr8:38654374-38654912 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27259 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27260 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27261 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27262 Neighboring gene ReSE screen-validated silencer GRCh37_chr8:38664233-38664424 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:38692400-38693183 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27263 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:38718798-38719298 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:38719299-38719799 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:38721554-38722054 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:38722055-38722555 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr8:38724712-38725911 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27266 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27265 Neighboring gene uncharacterized LOC124901937 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19137 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19138 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27267 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:38771665-38772346 Neighboring gene pleckstrin homology domain containing A2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:38793869-38794549 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:38794550-38795229 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27269 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27270 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19139 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27271 Neighboring gene Sharpr-MPRA regulatory region 15086 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:38853156-38853678 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:38853679-38854200 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27274 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27275 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19140 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27276 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27277 Neighboring gene TM2 domain containing 2 Neighboring gene ADAM metallopeptidase domain 9 Neighboring gene small nucleolar RNA, C/D box 38D

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. HtrA4 is required for human trophoblast stem cell differentiation into syncytiotrophoblast. Thach B, et al. Placenta, 2024 Mar 6. PMID 38325051
  2. Human HtrA4 Expression Is Restricted to the Placenta, Is Significantly Up-Regulated in Early-Onset Preeclampsia, and High Levels of HtrA4 Cause Endothelial Dysfunction. Singh H, et al. J Clin Endocrinol Metab, 2015 Jul. PMID 25946029
  3. HtrA4 may play a major role in inhibiting endothelial repair in pregnancy complication preeclampsia. Wang Y, et al. Sci Rep, 2019 Feb 25. PMID 30804477, Free PMC Article
  4. HtrA4 Protease Promotes Chemotherapeutic-Dependent Cancer Cell Death. Wenta T, et al. Cells, 2019 Sep 20. PMID 31546993, Free PMC Article
  5. Elevated circulating HtrA4 in preeclampsia may alter endothelial expression of senescence genes. Wang Y, et al. Placenta, 2020 Jan 15. PMID 32056555

See all (29) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Identification of HTRA4 as a Transcriptional Target of p63 in Trophoblast.
    Title: Identification of HTRA4 as a Transcriptional Target of p63 in Trophoblast.
  2. HtrA4 is required for human trophoblast stem cell differentiation into syncytiotrophoblast.
    Title: HtrA4 is required for human trophoblast stem cell differentiation into syncytiotrophoblast.
  3. Deficiency of HtrA4 in BeWo cells downregulates angiogenesis through IL-6/JAK/STAT3 signaling.
    Title: Deficiency of HtrA4 in BeWo cells downregulates angiogenesis through IL-6/JAK/STAT3 signaling.
  4. Cellular Functions of High-Temperature Requirement Factor A4 in Placenta.
    Title: Cellular Functions of High-Temperature Requirement Factor A4 in Placenta.
  5. HtrA4 is up-regulated during trophoblast syncytialization and BeWo cells fail to syncytialize without HtrA4.
    Title: HtrA4 is up-regulated during trophoblast syncytialization and BeWo cells fail to syncytialize without HtrA4.
  6. Elevated circulating HtrA4 in preeclampsia may alter endothelial expression of senescence genes.
    Title: Elevated circulating HtrA4 in preeclampsia may alter endothelial expression of senescence genes.
  7. HtrA4 may play a major role in inhibiting endothelial repair in pregnancy complication preeclampsia.
    Title: HtrA4 may play a major role in inhibiting endothelial repair in pregnancy complication preeclampsia.
  8. New insight into the mechanism of the HtrA4 protease function in cell death and oncogenesis; they may help to develop new anti-cancer therapeutic strategies.
    Title: HtrA4 Protease Promotes Chemotherapeutic-Dependent Cancer Cell Death.
  9. concentrations found in preeclampsia cleaved VE-cadherin in HUVECs as an endothelial model, disrupted cell-cell connections and induced intercellular gaps
    Title: Elevated protease HtrA4 in the maternal circulation of preeclampsia may contribute to endothelial barrier disruption by cleaving key junctional protein VE-cadherin.
  10. Discerning the mechanism of action of HtrA4: a serine protease implicated in the cell death pathway.
    Title: Discerning the mechanism of action of HtrA4: a serine protease implicated in the cell death pathway.
Submit: New GeneRIF Correction See all GeneRIFs (18)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

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

Homology

Clone Names

  • FLJ90724

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
  
Process Evidence Code Pubs
involved_in negative regulation of transforming growth factor beta receptor signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
  
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 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 HTRA4
Names
high-temperature requirement factor A4
probable serine protease HTRA4

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_153692.4 → NP_710159.1  serine protease HTRA4 precursor

    See identical proteins and their annotated locations for NP_710159.1

    Status: REVIEWED

    Source sequence(s)
    AC108863, AK075205, AY188774
    Consensus CDS
    CCDS6110.1
    UniProtKB/Swiss-Prot
    P83105, Q542Z4, Q6PF13
    UniProtKB/TrEMBL
    B4DTF7
    Related
    ENSP00000305919.4, ENST00000302495.5
    Conserved Domains (5) summary
    COG0265
    Location:156 → 470
    DegQ; Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones]
    cd00987
    Location:380 → 470
    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:40 → 94
    IGFBP; Insulin-like growth factor binding protein
    pfam07648
    Location:108 → 152
    Kazal_2; Kazal-type serine protease inhibitor domain
    pfam13365
    Location:202 → 340
    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_000008.11 Reference GRCh38.p14 Primary Assembly

    Range
    38974228..38988663
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011544431.3 → XP_011542733.1  serine protease HTRA4 isoform X1

    Conserved Domains (3) summary
    pfam00219
    Location:40 → 94
    IGFBP; Insulin-like growth factor binding protein
    pfam07648
    Location:108 → 152
    Kazal_2; Kazal-type serine protease inhibitor domain
    pfam13365
    Location:202 → 340
    Trypsin_2; Trypsin-like peptidase domain

  2. XM_011544432.2 → XP_011542734.1  serine protease HTRA4 isoform X2

    Conserved Domains (3) summary
    pfam00219
    Location:40 → 94
    IGFBP; Insulin-like growth factor binding protein
    pfam07648
    Location:108 → 152
    Kazal_2; Kazal-type serine protease inhibitor domain
    pfam13365
    Location:202 → 332
    Trypsin_2; Trypsin-like peptidase domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060932.1 Alternate T2T-CHM13v2.0

    Range
    39251369..39265805
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054359997.1 → XP_054215972.1  serine protease HTRA4 isoform X1

  2. XM_054359998.1 → XP_054215973.1  serine protease HTRA4 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P83105.1 GenPept UniProtKB/Swiss-Prot:P83105

Gene LinkOut

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