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FLASH GENE
Symbol HSPG2 contributors: mct/npt - updated : 20-08-2009
HGNC name heparan sulfate proteoglycan 2
HGNC id 5273
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • four domains homologous to the LDL receptor
  • the N terminal region of laminin A and B short arms
  • NCAM globular C terminus of the laminin A chain
  • 22 Ig-like domain
  • three laminin G like domains
  • glycosaminoglycan-bearing perlecan domain I that supports early chondrogenesis and growth factor delivery (Farach-Carson 2008)
  • peptide sequence (TWSKVGGHLRPGIVQSG) from an immunoglobulin (Ig) repeat in domain IV supported rapid cell adhesion, spreading and focal adhesion kinase (FAK) activation (Farach-Carson 2008)
  • four EGF-like domains
  • one SEA domain
  • four EGF-like domains
  • HOMOLOGY
    interspecies homolog to murine Plc
    Homologene
    FAMILY
  • syndecan family
  • CATEGORY secretory , structural protein
    SUBCELLULAR LOCALIZATION extracellular
    text
  • basement membrane
  • protein of extracellular matrix of cartilage
  • strong pericellular localization pattern in postnatal (2-7 month) and mature (55-64 year) femoral cartilages (Melrose 2006)
  • basic FUNCTION
  • linking the cytoskeleton to interstitial matrix
  • required to inhibit thrombosis after deep vascular injury, contributing to endothelial cell mediated inhibition of intimal hyperplasia
  • chains presumably participate in the selective permeability of basement membranes and, additionally, the core protein may be involved in a number of biological functions such as cell binding, LDL-metabolism, basement membrane assembly, calcium binding, and growth- and neurite-promoting activities (Kallunki 1992)
  • maintaining cartilage integrity and also regulating muscle excitability
  • playing an important role in chondrogenesis and skeletal development, as well as harboring pro- and anti-angiogenic activities
  • may be involved in cartilage collagen matrix assembly, and in extracellular matrix assembly
  • negatively regulates angiogenesis counter to its proangiogenic parental molecule
  • requires both the ITGA2 integrin and KDR for its angiostatic activity
  • novel antiangiogenic modality that could supplement established therapies in clinical use or in preclinical stages
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
  • major component of basement membranes
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with nidogen (NID,NID2), fibulin 2 (FBLN2), fibronectin (FN1, FN2), FGF7 (activation of its receptor)
  • with ECM1
  • bind directly and with high affinity to both KDR and FLT1, in a region that differs from VEGFA-binding site
  • cell & other
    REGULATION
    inhibited by TGF beta
    ASSOCIATED DISORDERS
    corresponding disease(s) DDSH , SJS1 , DDRD
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    Perlecan knock-in mice were developed to model Schwartz-Jampel syndrome (SJS), a skeletal disease resulting from decreased perlecan (Rodgers 2007)