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FLASH GENE
Symbol ADAMTS1 contributors: npt/SGE - updated : 25-09-2018
HGNC name ADAM metallopeptidase with thrombospondin type 1 motif, 1
HGNC id 217
Location 21q21.3      Physical location : 28.208.607 - 28.217.728
Synonym name
  • adamylysin
  • a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 1
  • Synonym symbol(s) METH1, KIAA1346, C3-C5, ADAM-TS1
    EC.number 3.4.24.-
    DNA
    TYPE functioning gene
    STRUCTURE 9.12 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • hypoxia-inducible factor binding sites, transcription mediated by HIF1 (Hatipoglu 2009)
  • 3'-UTR may regulate the expression of ADAMTS1 mRNA (Hatipoglu 2009)
  • MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 4670 105 967 - Lu (2009)
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Endocrineadrenal gland   moderately
     parathyroid   moderately
    Hearing/Equilibriumearinnercochlea highly
    Nervousnervecranial nerveoptic nerve moderately
    Reproductivefemale systemuterus  highly
     male systemprostate  highly
    Visualeyeuveachoroid moderately
     eyelens  moderately
     eyeretina  moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Epithelialbarrier liningretinal pigment epithelium (RPE) moderately
    Epithelialsecretoryglandularendocrinemoderately
    cell lineage
    cell lines retinal pigment epithelium cell line ARPE-19
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text placenta, kidney
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a signal peptide (5,1 kDa)
  • a propeptide domain
  • a reprolysin-type catalytic domain
  • two disintegrin loops, a disintegrin-like domain showed no structural homology to the disintegrin domains of other metalloproteinases such as ADAM10 but is instead very similar in structure to the cysteine-rich domains of other metalloproteinases (Gerhardt 2007)
  • a thrombospondin type 1 (TSP1) module
  • a cysteine rich domain, a spacer domain without cysteine residues, stacking against the active site, suggesting a possible regulatory role (Gerhardt 2007)
  • three C-terminal TSP-like modules, TSP type I motifs and the spacer region responsible for its experimental metastasis-inhibitory activity
  • conjugated MetalloP
    isoforms Precursor a 715 amino acids mature peptide (78.6 kDa)
    HOMOLOGY
    interspecies homolog to rattus Adamts1 (83.12 pc)
    homolog to murine Adamts1 (83.12 pc)
    Homologene
    FAMILY
  • ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    basic FUNCTION
  • cell surface adhesion protein, involved in mineralised nodule and bone formation
  • inflammation-induced gene inhibiting endothelial cell proliferation
  • may be implicated in cell migration in retina and in inflammatory eye diseases
  • blocking KDR phosphorylation with consequent suppression of endothelial cell proliferation
  • having anti-angiogenic activity
  • playing an important role for follicular development and involved in the organization of the medullary vascular network
  • capable of binding to and degrading extracellular matrix components (Lu 2009)
  • promotes tumor development through the induction of a stromal reaction (Rocks 2008)
  • involved in tissue remodelling, wound healing and angiogenesis (Gerhardt 2007)
  • inducing the cleavage of SEMA3C and promoting the migration of breast cancer cells, thus contributing to the metastatic program (Esselens 2010)
  • CELLULAR PROCESS cell life, proliferation/growth
    protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • cleaving aggrecan (ACAN) and pro-collagens
  • interacting with, cleaving, and modifying the extracellular location of THPI2
  • integrin
  • interacting with MMP1 (functional role of MMP1 and ADAMTS1 in promoting osteolytic bone metastasis) (Lu 2009)
  • FBLN1 regulates VCAN-dependent events in ventricular morphogenesis by promoting ADAMTS1 cleavage of VCAN leading to suppression of trabecular cardiomyocyte proliferation mediated by the ERBB2-Map kinase pathway
  • cell & other
  • heparin
  • REGULATION
    induced by hypoxia in endothelial cells (Hatipoglu 2009)
    Other up-regulated by TNF-alpha, IL1-bÍta and VEGF
    post-translationally processed by MMP2
    down-regulated by TGFB1
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    associated with various inflammatory processes as well as development of cancer cachexia
    constitutional     --over  
    in brain of patients with neurodegenerative disease leading to or reflecting pathological lesions in Down syndrome
    tumoral       loss of function
    ADAMTS1 gene inactivated through promoter hypermethylation in colorectal tumor development
          --over  
    strongly expressed in myocardial infarction (Hatipoglu 2009)
    tumoral     --over  
    promotes pulmonary metastasis of TA3 mammary carcinoma (Lu 2009)
    tumoral     --low  
    by aberrant methylation of ADAMTS1 in non-small cell lung cancer (Choi 2008)
    constitutional     --low  
    in the maternal and cord blood were lower in the preeclampsia group than in the control group
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • may be used as marker protein for neurodegeneration
  • molecular targeting of MMP1 and ADAMTS1, combined with inhibition of EGFR, may potentially reduce the risk of bone metastasis for a significant number of breast cancer patients (Lu 2009)
  • Marker
    Therapy target
    ANIMAL & CELL MODELS