Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol HTRA1 contributors: mct/shn/pgu - updated : 26-06-2017
HGNC name HtrA serine peptidase 1
HGNC id 9476
Corresponding disease
ARMD7 age-related macular degeneration, 7
CARASIL CARASIL syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leucoencephalopathy
Location 10q26.13      Physical location : 124.221.040 - 124.274.424
Synonym name
  • protease, serine, 11 (IGF binding)
  • IGFBP5-protease
  • serine protease HTRA1 (high-temperature requirement A1)
  • high-temperature requirement factor A1
    • Synonym symbol(s) PRSS11, HtrA, L56, ORF480, ARMD7, CADASIL2, CARASIL
    EC.number 3.4.21.-
    DNA
    TYPE functioning gene
    STRUCTURE 53.38 kb     9 Exon(s)
    MAPPING cloned Y linked N status provisional
    Map cen - D10S1679 - D10S1483 - HTRA1 - D10S587 - D10S1213 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 2138 - 480 - 2003 12513693
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
    Digestiveliver   highly
    Endocrinepancreas   lowly
    Nervousbrain   highly
    Reproductivefemale systemplacenta  predominantly Homo sapiens
    Respiratorylung   lowly
    Urinarykidney   moderately
    Visualeyeretina   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal lowly
    cell lineage
    cell lines tumor cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text skeletal elements
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a signal peptide
  • a Kazal-like domain
  • a serine protease domain
  • a signal sequence for secretion,
  • a partial insulin-like growth factor-binding protein-7 domain, serine protease domain resembling classic serine proteases such as trypsin
  • one C-terminal PDZ domain
    • HOMOLOGY
    interspecies ortholog to Htra1, Mus musculus
    ortholog to Htra1, Rattus norvegicus
    ortholog to HTRA1, Pan troglodytes
    Homologene
    FAMILY
  • HtrA serine protease family
  • peptidase S1B family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus
    text
  • secreted protein
  • intracellular HTRA1 was localized to microtubules and to the nucleus
    • basic FUNCTION
  • an antagonist of Tgfbeta family proteins
  • a candidate tumor suppressor involved in promoting serine-protease-mediated cell death
  • potential role as a predictive factor of clinical response to chemotherapy
  • a putative role in extracellular matrix homeostasis
  • decreases TGFB signaling through its protease activity and might play a pivotal role in human cerebral small-vessel disease
  • might likely function as a MAPT protease
  • plays a detrimental role in the pathogenesis of intervertebral disc (IVD) degeneration
  • promotes IVD degeneration through the proteolytic cleavage of fibronectin and subsequent activation of resident disc cells
  • likely a central role for HTRA1 in joint degeneration through its proteolytic actions on ECM components
  • HTRA1 and FGF8 may function coordinately in the common FGF signaling pathway
  • antagonizes TGFB1 signaling, and plays a key role in the regulation of bone formation
  • is produced as a secreted protein during osteoclastogenesis, and negatively regulates osteoblast differentiation
  • may likely mediate the fine tuning of paracrine and autocrine regulations during bone remodeling processes
  • HTRA1 and HTRA3 are crucial for trophoblast-decidual cell interaction in the control of trophoblast invasion
  • play a modulatory role in metastasis of hepatocellular carcinoma (HCC), and its expression was closely related to EMT, which might be a potential mechanism underlying metastasis of HCC
  • HTRA1, HTRA2, HTRA3, HTRA4 function as important modulators of many physiological processes, including maintenance of mitochondrial homeostasis, cell signaling and apoptosis
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • Bmp4, Gdf5, Tgfbeta 2, Tgfbeta 1 and activin
  • decreases TGFB-1 signaling via interaction with proTGF-B1 in the intracellular space (binds to and cleaves the pro-domain of proTGF-beta1 in the ER, resulting in a decreased amount of secreted mature TGF-beta)
  • degrades MAPT aggregates and is induced by its substrates
  • HTRA1 directly cleaves FGF8 in the extracellular region, and this cleavage results in decreased activation of FGF signaling, which is essential for many physiological processes
  • HTRA1 is a novel LRP1 ligand
  • decidua-secreted HTRA1 and HTRA3 antagonize HTRA4-mediated trophoblast invasion
    • cell & other
    REGULATION
    Other downregulated in ovarian cancer
    ASSOCIATED DISORDERS
    corresponding disease(s) ARMD7 , CARASIL
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    in tumor cell lines
    constitutional     --over  
    mRNA levels are elevated approximately 7-fold in cartilage from individuals with osteoarthritis compared with nonarthritic controls
    constitutional     --over  
    in dilated cardiomyopathy
    constitutional     --over  
    in osteoarthritic patients and as having the potential to regulate matrix metalloproteinase (MMP) expression in synovial fibroblasts through the generation of fibronectin fragments
    constitutional     --over  
    placental HTRA1 is significantly up-regulated in preeclampsia (PE) (significantly increased in early-onset PE, but significantly reduced in late-onset PE)
    Susceptibility to age-macular dgeneration (AMD)
    Variant & Polymorphism SNP , other
  • in the promoter region is a major genetic risk factor for wet AMD
  • polymorphism, rs11200638, is a strong candidate with a functional consequence that predisposes Japanese to develop neovascular AMD
  • HTRA1 expression is enhanced by AMD specific indel mutation in the promoter region of HTRA1 gene, and this enhanced HTRA1 may be concerned with induce retinal neovascularization , and AMD-associated silent polymorphisms in HTRA1 impair its ability to antagonize IGF1
    • Candidate gene
    Marker
  • significant increase of serum HTRA1 in early-onset PE suggests that it may be a potential biomarker for the diagnosis of early-onset preeclampsia (PE) at disease presentation
    • Therapy target
    SystemTypeDisorderPubmed
    osteoarticularbone 
    may represent a novel therapeutic target for the treatment of spinal disc degeneration
    ANIMAL & CELL MODELS