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FLASH GENE
Symbol ADAMTS1 contributors: mct - updated : 25-09-2018
HGNC name ADAM metallopeptidase with thrombospondin type 1 motif, 1
HGNC id 217
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-bêta 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
  • methylation status of ADAMTS1 and BNC1 in cfDNA shows promise for detecting pancreatic cancer during the early stages when curative resection of the tumor is still possible
  • Therapy target
    ANIMAL & CELL MODELS