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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
DNA
TYPE functioning gene
STRUCTURE 9.31 kb     9 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Binding site   silencer
text structure
  • 1 SP1 and 3AP2 sites (binding site)
  • 1 silencer element
  • MAPPING cloned Y linked N status provisional
    Map cen - D1S2844 - ADAMTS4 - D1S196 - qter
    Authors GeneMap (98)
    Physical map
    SLAMF7 1q23.1-q24.1 SLAM family member 7 LY9 1q21.3-q22 lymphocyte antigen 9 CD244 1q23.1 CD244 natural killer cell receptor 2B4 ITLN1 1q21.3 intelectin 1 (galactofuranose binding) LOC284679 1q23.1 similar to spermine synthase; spermidine aminopropyltransferase ITLN2 1q22-q23.5 intelectin 2 F11R 1q21.2-q21.3 F11 receptor USF1 1q22-q23 upstream transcription factor 1 LOC388708 1 similar to KAT protein LOC257106 1q23.1 hypothetical protein LOC257106 LNIR MGC33338 1q23.1 hypothetical protein MGC33338 PFDN2 1q23.1 prefoldin 2 NIT1 1q21-q22 nitrilase 1 DEDD 1q21.3 death effector domain containing HSPC155 1q23.1 hypothetical protein HSPC155 USP21 1q22 ubiquitin specific protease 21 PPOX 1q22 protoporphyrinogen oxidase B4GALT3 1q21-q23 UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 3 ADAMTS4 1q23 a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 4 NDUFS2 1q23 NADH dehydrogenase (ubiquinone) Fe-S protein 2, 49kDa (NADH-coenzyme Q reductase) FCER1G 1q23 Fc fragment of IgE, high affinity I, receptor for; gamma polypeptide APOA2 1q21-q23 apolipoprotein A-II FLJ12770 1q23.1 hypothetical protein FLJ12770 NR1I3 1q23.1 nuclear receptor subfamily 1, group I, member 3 MPZ 1q22 myelin protein zero (Charcot-Marie-Tooth neuropathy 1B) SDHC 1q21 succinate dehydrogenase complex, subunit C, integral membrane protein, 15kDa LOC257177 1q23.1 similar to hypothetical protein MGC20470 LOC148430 1q23.1 similar to ribosomal protein S2; 40S ribosomal protein S2 LOC388709 1 LOC388709 LOC388710 1 LOC388710
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 4410 98 837 - 2010 2066492
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain    
     nervecranial nerve   
    Respiratoryrespiratory tracttrachea   
    Urinarykidney   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
     chondrocyte
    cell lineage
    cell lines osteoarthritic cartilage
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    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