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FLASH GENE
Symbol PRG4 contributors: mct/npt - updated : 21-12-2016
HGNC name proteoglycan 4
HGNC id 9364
Corresponding disease
CACP camptodactyly- arthropathy-coxa varapericarditis syndrome
Location 1q31.1      Physical location : 186.265.404 - 186.283.686
Synonym name
  • lubricin
  • megakaryocyte stimulating factor
  • proteoglycan 4, (megakaryocyte stimulating factor, articular superficial zone protein, camptodactyly, arthropathy, coxa vara, pericarditis syndrome)
  • bG174L6.2 (MSF: megakaryocyte stimulating factor)
  • articular superficial zone protein
  • superficial zone proteoglycan
  • Synonym symbol(s) MSF, SZP, HAPO, JCAP, bG174L6.2, FLJ32635, CACP
    DNA
    TYPE functioning gene
    STRUCTURE 18.28 kb     13 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 5059 - 1404 - 2013 23599181
    exon 1-6
    12 splicing 4936 - 1363 same as PRG4A 2013 23599181
    skipping exon 2
    11 splicing 4780 - 1311 same as A + catilage 2013 23599181
    skipping exon 4 and 5
    10 splicing 4657 - 1270 predominantly in cartilage 2013 23599181
    skipping exon 2, 4, 5
    13 - 4921 - 1361 - 2013 23599181
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver    
    Endocrinepancreas    
    Lymphoid/Immunespleen    
     thymus   highly
    Reproductivefemale systemuteruscervix highly
     male systemprostate  highly
    Respiratorylung    
    Skeletonappendicularjoint    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Connectivecartilagefibrocartilage   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    not specificsynoviocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text placenta, spleen
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal somatomedin B-like domain
  • heparin binding site
  • chondroitin sulfate attachment site
  • oloigosaccharide attachment sites
  • mucin-like repeat in the central region
  • a C terminal T rich region
  • conjugated GlycoP
    HOMOLOGY
    Homologene
    FAMILY plasticity-related gene family
    CATEGORY regulatory , secretory
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    basic FUNCTION
  • regulator of ossification
  • regulator of intimal cell growth
  • mucin-like proteoglycan that is a major lubricant in articulating joints
  • superficial zone protein (SZP), an important joint lubricant produced by superficial zone, that are more responsive to stimulation by catabolic cytokines such as IL1 (Taniguchi 2009)
  • synovial glycoprotein that has been shown to be a boundary lubricant (Gleghorn 2009)
  • brain-specific integral membrane protein implicated in neuronal plasticity, such as filopodia formation and axon growth after brain lesion (Broggini 2010)
  • having lubricating and protective actions in joints
  • critical protective factor in articular joints, is implicated in hematopoietic progenitor cell expansion and megakaryopoiesis
  • may have a role in normal disc posterior attachment physiology through the prevention of cellular adhesion as well as providing lubrication during normal bilaminar zone function
  • is likely able to bind to polymorphonuclear granulocytes (PMN) via an L-selectin-dependent and -independent manner and may play a role in PMN-mediated inflammation
  • PRG4 presence significantly reduces friction between the cornea and conjunctiva and its deficiency may play a role in promoting corneal damage
  • important role of PRG4 in mediating interactions at the cartilage surface is to attach to the cartilage surface
  • PRG4 (lubricin) is a novel putative ligand for CD44 and may control synoviocyte overgrowth in inflammatory arthropathies via a CD44-mediated mechanism
  • mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes, that has a homeostatic multifaceted role in the joint
  • plays an important role in regulating the inflammatory environment under both homeostatic and tissue injury states
  • serves as a lubricant in joints, tendons and visceral cavities (pleural cavity, pericardium) and inhibits synovial proliferation
  • plays a role in controlling inflammation and pain as well as being a mechanical lubricant
  • adult talar cartilage increases both the PRG4 release and biosynthetic activity as an immediate cellular response to injury
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    text ossification
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PRG4 is a PTH-responsive gene in bone and liver
  • is a dynamic regulator of skeletogenesis and PTH skeletal anabolism
  • is a novel PTH-responsive factor regulating immune cells and PTH actions on marrow hematopoietic progenitor cells
  • PRG4 binds to TLR2 and TLR4 and this binding mediates a novel anti-inflammatory role for PRG4
  • may play a role in modulating inflammatory responses through interaction with CD44
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) CACP
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in synovial fluid associated with an increase in levels of inflammatory cytokines (Elsaid 2008)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • association of PRG4 concentration in synovial fluid and clinical status of osteoarthritic knee
  • Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmunearticular
    supplementation of synovial fluid with PRG4 may be an effective treatment to prevent cartilage deterioration in patients with genetic or acquired deficiency of PRG4
    ANIMAL & CELL MODELS
  • adult Prg4 mutant mice had decreased trabecular and cortical bone, and blunted PTH-mediated increases in bone mass