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

Summary

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: mouse all
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Genomic context

Location:: 8p11.22

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (38974228..38988663)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (39251369..39265805)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (38831747..38846182)

Chromosome 8 - NC_000008.11 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?

HtrA4 is required for human trophoblast stem cell differentiation into syncytiotrophoblast.
Title: HtrA4 is required for human trophoblast stem cell differentiation into syncytiotrophoblast.
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.
Cellular Functions of High-Temperature Requirement Factor A4 in Placenta.
Title: Cellular Functions of High-Temperature Requirement Factor A4 in Placenta.
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.
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.
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.
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.
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.
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.
The HtrA1-PDZ and HtrA4-PDZ as well as HtrA2-PDZ and HtrA3-PDZ respond similarly to different halogen substitutions of peptide; -Br substitution at R2-position and -I substitution at R4-position are most effective in improving peptide selectivity for HtrA1-PDZ/HtrA4-PDZ and HtrA2-PDZ/HtrA3-PDZ, respectively; -F substitution would not address substantial effect on peptide selectivity for all the 4 domains
Title: Peptide selectivity between the PDZ domains of human pregnancy-related serine proteases (HtrA1, HtrA2, HtrA3, and HtrA4) can be reshaped by different halogen probes.

Submit: New GeneRIF Correction See all GeneRIFs (17)

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 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

RH36052 (e-PCR)
- UniSTS:14644

STS-H42485 (e-PCR)
- UniSTS:14153

NoName (e-PCR)
- UniSTS:481616

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)

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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

38974228..38988663

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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