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FLASH GENE
Symbol ACAN contributors: mct/npt - updated : 16-12-2019
HGNC name aggrecan
HGNC id 319
Corresponding disease
FOD osteochondritis dissecans familial
SEDMA spondyloepiphyseal dysplasia, Kimberley type
SEMDAG spondyloepimetaphyseal dysplasia, aggrecan type
Location 15q26.1      Physical location : 89.346.673 - 89.418.585
Synonym name
  • chondroitin sulfate proteoglycan 1
  • large aggregating proteoglycan
  • aggrecan 1 (chondroitin sulfate proteoglycan 1, large aggregating proteoglycan, antigen identified by monoclonal antibody A0122)
  • cartilage-specific proteoglycan core protein
  • Synonym symbol(s) CSPG1, CSPGCP, MSK16, AGC1, SEDK, AGCAN, CSPCP, AGN, SSOAOD
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    text component of a cluster of paralogous genes on chromosomes 15 and 19
    STRUCTURE 71.92 kb     16 Exon(s)
    MAPPING cloned Y linked N status confirmed
    Map see TM6SF1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 splicing 8543 250.4 2431 moderately in skin and connective tissues, lowly in colon 2014 19298220
  • lacking two different segments in the C-terminus compared to variant 2
  • lacking the EGF-like and CRP-like domains
  • being the most predominant transcript
  • a 19 aa signal peptide of 2.1 kda
  • a 2298 aa mature peptide of 237.3 kda
  • 18 splicing 8840 261.3 2530 predominantly in connective tissues, highly in bone and moderately in trachea 2014 19298220
  • a 19 aa signal peptide of 2.1 kda
  • a 2397 aa mature peptide if 248.3 kda
  • containing the EGF-like and CRP-like domains in the C terminus
  • 19 - 8960 - 2568 - 2014 19298220
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Skeletonaxial skeletonvertebral columnvertebrae   Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivecartilage  highly Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    Text highly in developing cartilage, in the pre-hypertrophic zone of the growth plate (Aoyama 2009)
    PROTEIN
    PHYSICAL PROPERTIES Hydrophobic
    STRUCTURE
    motifs/domains
  • six calpain cleavage sites: one in the IGD
  • (interglobular domain), one in the KS (keratan sulfate) region, two
    in the CS1 and two in the CS2 region
  • a 19 aa signal peptide
  • an Ig-like V-type (immunoglobulin-like) domain
  • four Link domains
  • an EGF-like domain
  • a C-type lectin domain
  • a complement regulatory-like Sushi (CCP/SCR) domain
  • three globular domains (G1, G2 and G3) and a GAG-attachment domain to which multiple chondroitin sulfate and keratan sulfate chains are attached (Aoyama 2009)
  • a hydrophobic transmembrane segment (TM)
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine Agc1
    homolog to C.elegans f40f4.6
    intraspecies paralog to CSPG3
    Homologene
    FAMILY
  • aggrecan/Versican proteoglycan family
  • CATEGORY adhesion , structural protein
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,lysosome
    text
  • being a major component of extracellular matrix of cartilagenous tissues
  • is initially expressed within the growth plate but is lost during the course of calcification
  • is a major proteoglycan in the intervertebral disc and end plate
  • basic FUNCTION
  • playing a role in the resistance to the compression in cartilage
  • major proteoglycan of the extracellular matrix in cartilage (Aoyama 2009)
  • playing a critical role in regulating matrix assembly (Stattin 2010)
  • plays an important role in the organization of the neural extracellular space by binding and organizing hyaluronan to the cell surface through interactions with link protein and tenascins forming a large aggregated quaternary complex
  • critical role for perineuronal nets and aggrecan in regulating developmental neural plasticity and in the recover from injury
  • chondroitin sulfate proteoglycan core protein aggrecan is the major protein constituent of cartilage aside from collagen, and is largely responsible for its distinctive mechanical properties
  • required both for proper cartilage formation in development and maintenance of mature cartilage
  • ACAN, link protein and tenascin-R are essential components of the perineuronal net to protect neurons against iron-induced oxidative stress
  • a major component of cartilage extracellular matrix
  • has a major role in regulating the expression of key growth factors and signaling molecules during development of cartilaginous tissue and is essential for proper chondrocyte organization, morphology, and survival during embryonic limb development
  • is required for outflow tract (OFT) development and when its expression is reduced this is associated with bicuspid aortic valves (BAV)
  • ACAN and FBLN1 have likely critical roles in determining the biomechanics of the aorta and their modification with age could underpin age-related aortic stiffening
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text
  • skeletal development
  • PATHWAY
    metabolism
    signaling
    a component
  • prominent component of the extracellular matrix in growth plate cartilage
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with FBLN1
  • interacting with CTGF (may contribute to the physiological distribution of CCN2/CTGF in the growth plate of cartilage) (Aoyama 2009)
  • several enhancers contain potential binding sites for SOX9, consistent with its described role as an upstream regulator of ACAN expression
  • IL6 mediates suppression of ACAN and induction of MMP13 expression by NOTCH1 in chondrocytes
  • SHOX2 activates ACAN via its cooperation with SOX5, SOX6, SOX9 4)
  • deacetylation promotes SOX9 nuclear translocation and hence its ability to activate ACAN
  • cell & other
  • binding avidly to hyaluronic acid via an N-terminal globular region
  • binding to sugar
  • REGULATION
    activated by SOX9
    Other regulated by the cooperation of SHOX with the SOX trio (SOX5, SOX6 and SOX9) via the protein interaction between SOX5/SOX6 and SHOX
    ASSOCIATED DISORDERS
    corresponding disease(s) SEDMA , FOD , SEMDAG
    Susceptibility
  • to multiple disc degeneration in the subjects below the age of 40 years
  • to non-syndromic short stature
  • Variant & Polymorphism repeat
  • carrying a copy of the allele with 21 repeats might increase the risk of multiple disc degeneration in the subjects below the age of 40 years
  • truncating variants at the 5' end of ACAN gene co-segregate with severe short stature phenotype
  • Candidate gene
    Marker
  • potential novel biomarker which might be used for prediction of lumbar degenerative disc disease (LDDD) risk
  • Therapy target
    ANIMAL & CELL MODELS
    Cmd (cartilage matrix deficiency) homologpus mice