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FLASH GENE
Symbol VCAN contributors: shn - updated : 04-03-2019
HGNC name versican
HGNC id 2464
DNA
TYPE functioning gene
STRUCTURE 110.63 kb     15 Exon(s)
regulatory sequence Promoter (TATA box)
Binding site   transcription factor
text structure
  • a typical TATA box located approximately 16 base pairs upstream of the transcription start site and binding sites for a number of transcription factors involved in regulated gene expression
  • several transcriptional regulatory elements were identified in the proximal promoter, including AP-1, Sp1, AP-2, and two TCF-4 site (Domenzain-Reyna 2009)
  • AP-1 and TCF-4 binding sites are the main regulatory regions directing versican production provide new insights into versican promoter regulation during melanoma progression (Domenzain-Reyna 2009)
    • MAPPING cloned Y linked N status confirmed
    Map cen - D5S2094 - D5S1959 - VCAN - D5S1948 - D5S459 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 splicing 12416 372 3396 localized in most smooth muscle tissues, fibrous and elastic cartilage, central and peripheral nervous system, basal layer of the epidermis, luminal surface of some glandular epithelia, in all three wall layers of veins and elastic arteries 2006 8601689
    also known as PG-M(V0)
    14 splicing 9455 - 2409 localized in most smooth muscle tissues, fibrous and elastic cartilage, central and peripheral nervous system, basal layer of the epidermis, luminal surface of some glandular epithelia, in all three wall layers of veins and elastic arteries 2006 8601689
  • also known as PG-M(V1)
  • lacking the CS alpha domain
  • promoted a "switch" in cadherin expression from N- to E-cadherin, resulting in epithelial specific adhesion junctions.
  • reduced vimentin levels and induced expression of occludin, an epithelial-specific marker
    • 14 splicing 7154 - 1642 major variant of the brain, highly expressed in the mature brain 2006 16452631
  • also known as PG-M(V2)
  • lacking the CS beta domain
  • cleaved by ADAMTS4 at Glu405-Gln406 to generate glial hyaluronate binding protein
  • fibronectin was up-regulated by V2 and mediated V2 function
  • could be a potential target for intervention of brain tumor angiogenesis (PMID: 23201264)
    • 13 - 4193 - 655 - 2006 16452631
  • lacking both the CS alpha and beta domains
  • also known as PG-M(V3)
    		•
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
     vesselsaorta  highly
    Digestiveliver   lowly
    Hearing/Equilibriumearinnercochlea moderately
    Nervousbrain   highly
     nerve   moderately
    Reproductivefemale systemplacenta  moderately
     male systemprostate  lowly
    Respiratoryrespiratory tractlarynx  highly
    Skin/Tegumentskin appendageshairfollicle lowly
    Visualeye   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connective   moderately
    Epithelialsensorygustatory  
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
     digestive
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text disappearance after the cartilage development
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal globular domain with two putative GAG, hyaluronic acid-binding domains,
  • a lectin-like sequence
  • middle region of the versican core protein is encoded by two large exons that encode for the GAG attachment regions (subdomains GAG- alpha and GAG-beta
  • a G1 domain, which contains two Link modules that bind to hyaluronan (HA), may be central to role in impacting proliferation, adhesion, pericellular matrix composition, and elastogenesis
  • a complement regulatory-like domain (sushi structure), in the C terminal region
    • isoforms Precursor a 3376 amino acids mature peptide (370,5 kDa)
    HOMOLOGY
    interspecies ortholog to VCAN, Pan troglodytes
    homolog to Vcan, Rattus norvegicus
    ortholog to Vcan, Mus musculus
    Homologene
    FAMILY
  • aggrecan/versican proteoglycan family
  • lectican family
    • CATEGORY adhesion , protooncogene
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,lysosome
    basic FUNCTION
  • a modular proteoglycan involved in the control of cellular growth and differentiation
  • chondroitin sulfate proteoglycan, likely playing an essential role both in mesenchymal condensation and in hair induction
  • intercellular signaling and connecting cells with the extracellular matrix
  • large chondroitin sulfate proteoglycan, which, in vitreous, binds to hyaluronan and link protein and forms large aggregates that are important for maintaining structural integrity
  • amy be playing a role in regulating aqueous humor outflow and intraocular pressure via the trabecular meshwork (HTM) of the eye
  • mediates mesenchymal-epithelial transition
  • connects microfibrils to the hyaluronan-rich matrix for viscoelasticity
  • large chondroitin sulfate proteoglycan of the extracellular matrix that is involved in a variety of cellular processes
  • plays a role in cell adhesion, migration, proliferation, epithelial-mesenchymal transition, differentiation, invasiveness, angiogenesis, and apoptosis
  • facilitates chondrogenesis and joint morphogenesis, by localizing TGF-beta in the extracellular matrix and regulating its signaling
  • DSPP, MEPE, VCAN, OGN play complementary roles during odontogenesis
  • regulates the development of peritoneal metastasis originating from cells and spheroids
  • potential intracellular function for VCAN in vascular cells where it appears to play a role in mitotic spindle organization during cell division
  • possible role of VCAN in modulating hepatic fibrogenesis
  • possible role of VCAN in ovulatory dysfunction and in the pathogenesis of PCOS (polycystic ovary syndrome)
  • macrophage-derived VCAN is likely an immunomodulatory molecule with anti-inflammatory properties in acute pulmonary inflammation
  • is a key regulator in human colon cancer development and progression involved in cell adhesion, proliferation, migration and angiogenesis and plays a central role in tissue morphogenesis and maintenance
    • CELLULAR PROCESS cell life
    cell communication
    PHYSIOLOGICAL PROCESS development
    text control of cell proliferation and differentiation
    PATHWAY
    metabolism
    signaling
    a component
  • extracellular matrix compoment
  • major hyaluronan-binding component in the dermis
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • fibulin 1, FBLN1
  • fibulin 2, FBLN2
  • L-selectin, P-selectin, and CD44
  • CXC chemokines gamma interferon-inducible protein 10 (IP-10), platelet factor 4, and SDF-1beta, the C chemokine lymphotactin, and the CC chemokines MCP-1, MCP-2, RANTES, liver and activation-regulated chemokine (LARC), and SLC
  • fibrillin 1, FBN1
  • integrin beta 1, ITGB1
  • hyaluronan, HA and link protein, LP
  • P-selectin glycoprotein ligand-1, PSGL-1
  • FBLN1 regulates VCAN-dependent events in ventricular morphogenesis by promoting ADAMTS1 cleavage of VCAN leading to suppression of trabecular cardiomyocyte proliferation mediated by the ERBB2-Map kinase pathway
  • enhanced PAPSS2/VCAN sulfation axis is essential for SNAI1-mediated breast cancer cell migration and metastasis
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) WGN1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    overexpressed in medulloblastomas, gliomas, schwannomas, neurofibromas mennigiomas
    constitutional somatic mutation      
    Wagner disease and erosive vitreoretinopathy (ERVR) are caused by mRNA isoform balance shifts. Representing a novel disease mechanism.
    constitutional       loss of function
    loss of the Hyaluronan (HA)-binding ability of versican followed by HA exclusion may be responsible for the pathological and phenotypical changes observed in solar elastosis
    tumoral     --over  
    overexpressed in cutaneous melanomas as well as in premalignant lesions, contributes to melanoma progression, favoring the detachment of cells and the metastatic dissemination
    tumoral     --over  
    in cervical carcinoma (expression can serve as an indicator of poor prognosis in patients with cervical cancer)
    tumoral     --over  
    in colon cancer and increased expression of VCAN was associated with the progression of colon cancer
    constitutional     --low  
    in patients with PCOS (polycystic ovary syndrome)
    tumoral     --over  
    in leiomyosarcoma
    Susceptibility to intracranial aneurysms
    Variant & Polymorphism SNP increasing the risk of intracranial aneurysms
    Candidate gene
    Marker
  • may be as biomarker for identification of the pathological grade of colon cancer
  • has biomarker potential for renal cell cancer
    • Therapy target
    SystemTypeDisorderPubmed
    cancerurinary 
    has therapeutic potential for renal cell cancer
    cancermuscle 
    role for using VCAN as a point of control in the management and treatment of leiomyosarcoma
    ANIMAL & CELL MODELS