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FLASH GENE
Symbol HTRA1 contributors: mct/shn/pgu - updated : 26-06-2017
HGNC name HtrA serine peptidase 1
HGNC id 9476
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