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FLASH GENE
Symbol ADAMTS4 contributors: mct - updated : 18-09-2015
HGNC name ADAM metallopeptidase with thrombospondin type 1 motif, 4
HGNC id 220
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a signal sequence
  • a propeptide domain
  • a reprolysin-type catalytic domain
  • a zinc catalytic domain
  • non-catalytic ancillary domains, including a disintegrin domain (Dis)
  • a thrombospondin domain
  • a cysteine-rich domain (Cysr)
  • a spacer domain (Sp) without cysteine residues
  • a C- terminal TSP-like module implicated in aggrecanolytic activity, and governing the specificity of the enzymes by modulating substrate binding, and affect the structure around the active site, favouring interaction with TIMP3
  • conjugated MetalloP
    isoforms Precursor pro-form of ADAMTS-4 is not catalytically active and only a limited number of mechanisms mediate its N-terminal activation
    HOMOLOGY
    interspecies homolog to murine secretory protein
    Homologene
    FAMILY
  • ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family
  • CATEGORY adhesion , enzyme
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • degrading the chondroitine sulfate proteoglycan (brevican)
  • playing a pivotal role in inflammatory joint disease, and in cartilage aggrecan degradation
  • epigenetically regulated and plays a role in aggrecan degradation in osteoarthritis
  • ADAMTS4 and ADAMTS5 not only play roles in the breakdown of cartilage extracellular matrix in osteoarthritis, but also mediate processing of matrilins in the secretory pathway
  • proteinase thought to be involved in processes ranging from cartilage metabolism to ovarian follicle development
  • ADAMTS1 and ADAMTS4 play redundant and essential roles in perinatal kidney development
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, cofactor,
  • Zn2+
  • protein
  • aggrecan (binding by TPS1motif) for cleavage of aggrecan
  • interacting with adaptor proteins and RAS, that synergistically regulate IL1-induced ADAMTS4 expression in chondrocytes (
  • ADAMTS4 cleaves RELN in an isoform-specific manner
  • cell & other
    REGULATION
    induced by interleukin 1
    inhibited by TIMP3
    alpha(2)-macroglobulin in a concentration-dependent manner,
    Other its expression was found to be regulated by EWS-FLI1 fusion gene-dependent manner
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    required to inhibit aggrecan degradation in human OA cartilage
    tumoral     --over  
    in Ewing sarcoma
    constitutional     --over  
    in acute coronary syndrome
    constitutional     --low  
    in the maternal and cord blood were lower in the preeclampsia group than in the control group
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • is potentially a novel tumor marker for Ewing sarcoma
  • its expression may be a valuable marker for predicting the severity of acute coronary syndrome
  • Therapy target
    ANIMAL & CELL MODELS