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FLASH GENE
Symbol ADAMTS5 contributors: mct - updated : 25-08-2014
HGNC name ADAM metallopeptidase with thrombospondin type 1 motif, 5
HGNC id 221
Location 21q21.3      Physical location : 28.290.231 - 28.339.439
Genatlas name Adamalysin-like metalloproteinase with thrombospondin motifs 5
Synonym name
  • aggrecanase 2
  • a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 5 (aggrecanase-2)
  • Synonym symbol(s) ADAMTS11, ADMP2, ATS5, FLJ36738
    EC.number 3.4.24.-
    DNA
    TYPE functioning gene
    STRUCTURE 49.21 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • a regulatory region associated with the gene ADAMTS5 that encompasses the entirety of the essential coding exon 2
  • MAPPING cloned Y linked N status provisional
    Physical map
    LOC284821 21q21.2 similar to ribosomal protein L13a; 60S ribosomal protein L13a; 23 kD highly basic protein C21orf42 21q21.3 chromosome 21 open reading frame 42 BIC 21q21 chromosome 21 open reading frame 42 MRPL39 21q11.2-q21 mitochondrial ribosomal protein L39 JAM2 21q21.2 junctional adhesion molecule 2 FDXP2 21q21.3 ferredoxin pseudogene 2 ATP5J 21q21.1 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit F6 GABPA 21q21.2-q21.3 GA binding protein transcription factor, alpha subunit 60kDa APP 21q21.2 amyloid beta (A4) precursor protein (protease nexin-II, Alzheimer disease) CYYR1 21q21.2 cysteine and tyrosine-rich 1 ADAMTS1 21q22.1-q22 a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 1 ADAMTS5 21q22.1-q22 a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 5 (aggrecanase-2) GPXP2 21q21.3 glutathione peroxidase pseudogene 2 EIF4A1P 21q21.2 eukaryotic translation initiation factor 4A, isoform 1, pseudogene RPL10P1 21q21.3 ribosomal protein L10 pseudogene 1 C21orf94 21q21.3 chromosome 21 open reading frame 94 C21orf100 21q22.1 chromosome 21 open reading frame 100 C21orf127 21q21.3 chromosome 21 open reading frame 127 HSPDP7 21q22.11 heat shock 60kDa protein 1 (chaperonin) pseudogene 7 LOC391276 21 similar to hypothetical protein ZNF294 21q22-q22.1 zinc finger protein 294 RPL23P2 21q22.11 ribosomal protein L23 pseudogene 2 C21orf6 21q22.1 chromosome 21 open reading frame 6 USP16 21q21 ubiquitin specific protease 16
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 9663 101.7 930 - 2008 18478108
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    digestiveesophagus    
    Nervousbrain    
    Reproductivefemale systemuteruscervix  
    Urinarybladder    
    Visualeyeretina   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivecartilage   
    Membrane    
    skeletonsynovium   
    cell lineage chondroblastoma
    cell lines osteoarthritis cartilage
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text peri-implantation period in mouse embryo, 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
  • a disintegrin domain (Dis)
  • a thrombospondin domain
  • a cysteine-rich domain (Cysr)
  • a spacer domain (Sp)
  • a second thrombospondin domain follows the spacer domain
  • one C terminal TSP-like module, that govern the specificity of the enzymes by modulating substrate binding
  • CysR and Sp domains greatly increased its aggrecanolytic activity
  • C-terminal domains affect the structure around the active site, favouring interaction with TIMP3
  • conjugated MetalloP
    isoforms Precursor
    HOMOLOGY
    interspecies homolog to murine Adamts5
    Homologene
    FAMILY
  • ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • cell surface adhesion protein cleaving the cartilage proteoglycan aggrecan, involved in the destruction of aggrecan in arthritic disease
  • may play a role in glioma cell invasion through the cleavage of brevican
  • major aggrecanase in cartilage metabolism and pathology
  • (aggrecanolytic activity of ADAMTS5 was much greater than ADAMTS4)
  • 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
  • in the growth plate ADAMTS5, and not ADAMTS4, has a physiological function in the intracellular processing of matrilins and potentially of other extracellular matrix proteins
  • role of ADAMTS5 in tendon is to remove pericellular and interfibrillar aggrecan to maintain the molecular architecture responsible for normal tissue function
  • a function of ADAMTS5 in dermal fibroblasts is potentially to maintain optimal versican content and pericellular matrix volume by continually trimming versican in hyaluronan-versican aggregates
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS locomotion
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • interaction with Syndecan-4 (controls the activation of ADAMTS5 through direct interaction with the protease and through regulating mitogen-activated protein kinase (MAPK)-dependent synthesis of MMP3)
  • LRP1 dictates physiological and pathological catabolism of aggrecan in cartilage and is a key modulator of the extracellular activity of ADAMTS5
  • RELA is a potent transcriptional activator of ADAMTS5 in chondrocytes during osteoarthritis development
  • role for SDC4 in mediating matrix degradation in both intervertebral discs and cartilage by controlling ADAMTS5 function and MMP3 expression
  • cell & other
    REGULATION
    induced by alpha(2)-macroglobulin in a concentration-dependent manner
    inhibited by TIMP3
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in glioblastoma cells
    constitutional     --low  
    required to inhibit aggrecan degradation in osteoarthritis cartilage
    constitutional     --low  
    during chondrogenesis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • adult Adamts5(-/-) mice are viable, they do not recover from developmental valve anomalies, but have myxomatous cardiac valves