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

    Gene ID: 203100, updated on 10-Dec-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
    mouse all
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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: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 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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    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

    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

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

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