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FLASH GENE
Symbol SPARC contributors: mct - updated : 02-07-2015
HGNC name secreted protein, acidic, cysteine-rich (osteonectin)
HGNC id 11219
Corresponding disease
OIXVII Osteogenesis imperfecta, type XVII
Location 5q33.1      Physical location : 151.041.018 - 151.066.517
Synonym name
  • osteonectin
  • cysteine-rich protein
  • basement-membrane protein 40
  • Synonym symbol(s) BM-40, BM40, OSN, ON
    DNA
    TYPE functioning gene
    STRUCTURE 25.96 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Map see CSF1R
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 3178 43 303 - 2007 16044147
    10 - 3601 - 302 - 2007 16044147
    - - 3602 - 341 - 2007 16044147
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas   highly Homo sapiens
    Hearing/Equilibriumear   highly
    Nervousbrain     Mus musculus
    Reproductivefemale systemuterus    Mus musculus
     female systemovary    Mus musculus
     male systemprostate    Rattus norvegicusFetal
    Skin/Tegumentskin   highly
    Urinarykidneynephron   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Connectivebone  highly
    Membranebasement   
    Muscularsmoothvessel  
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrine  Homo sapiens
    Nervousastrocyte Homo sapiens
    Nervousglia Homo sapiens
    Skeletonosteoblast Homo sapiens
    Urinaryepithelial cell
    Urinarytubular cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text mineralized tissues, cochlea, kidney
    PROTEIN
    PHYSICAL PROPERTIES acid
    STRUCTURE
    motifs/domains
  • a follistatin-like N terminal domain
  • Kazal type serine protease inhibitor domain
  • a C-terminal extracellular EF-hand calcium-binding (EC) domain, cysteine rich containing an EF-hand calcium binding motif and an acidic region
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine Sparc (92.7pc)
    homolog to rattus Sparc (93.0pc)
    Homologene
    FAMILY
  • matricellular protein family
  • CATEGORY chaperone/stress , regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,granule
    text
  • basement membrane
  • preferentially secreted by limbal fibroblasts
  • basic FUNCTION
  • extracellular calcium-binding protein, regulator of cell growth (osteonectin/BM40) and activator of MMP2 at the cell surface
  • contributing to the proteolytic pathway associated with tumor invasion
  • functioning as an endogenous inhibitor of cell proliferation, regulating angiogenesis, cell adhesion to extracellular matrix, binding cytokines such as platelet derived growth factor and stimulating transforming growth factor-beta (TGF-beta) production
  • invoved in the regulation of tumor growth, with THBS1 and FN1
  • may modulate intercellular adhesion of basal limbal epithelial cells
  • potentiated apoptosis by increasing caspase-8 signaling
  • functions, in part, to promote tumor progression by enabling tumor cells to survive under stressful conditions
  • matricellular glycoprotein, mediating interactions between cells and their extracellular matrix, and playing a role in in extracellular matrix organization
  • involved in collagen fibrillogenesis
  • protects cells from stress-induced apoptosis via an interaction with integrin beta 1 heterodimers that enhances ILK activation and pro-survival activity
  • function as a tumor suppressor in ovarian cancer, pancreatic cancer and acute myeloid leukemia
  • molecular chaperone that guides the folding of basement membrane proteins
  • impairs the proliferation of different cell types and modulates tumor cell aggressive features
  • matricellular protein that is highly expressed during development, tissue remodeling, and repair
  • suppresses apoptosis of idiopathic pulmonary fibrosis fibroblasts throug hconstitutive activation of beta catenin
  • secreted protein that binds to collagen type I in the extracellular space, it might also play a role as an intracellular chaperone of collagen type I
  • potentially important contributor to adipocyte differentiation and fat metabolism
  • involved in PRKAA1-regulation of glucose metabolism
  • strong inducer of autophagy as well as apoptosis
  • its expression induces autophagy, which results in the elevation of cathepsin B (CTSB) and subsequent mitochondria-mediated apoptosis
  • matrix cellular protein, which governs diverse cellular functions and has a pivotal role in regulating cell-matrix interactions, cellular proliferation and migration
  • promotes cellular deadhesion and motility in wound healing
  • participates in the regulation of morphogenesis and cellular differentiation through its modulation of cell-matrix interactions
  • induces potentially expression of neuronal markers in medulloblastoma cells through its inhibitory effect on IL6-regulated suppression of Notch pathway-mediated STAT3 signaling
  • SPARC functions through activation of AKT1 and MDM2 to limit TP53 levels
  • promotes pericyte migration by diminishing TGFB1 activity and identify a novel function for endoglin in controlling pericyte behavior
  • SPARC targets STAT3 signaling network induce growth arrest
  • secreted extracellular matrix glycoprotein with counter-adhesive properties, functioning to promote breast cancer invasion
  • matricellular protein with important roles in cell-extracellualr matrix interactions
  • regulator of microglial proliferation and structure, and may play an important role in differently regulating the gray and white matter microglial responses to CNS lesion--and modulating behavioral recovery--after injury
  • has a pathogenic role in the alteration of the extracellular matrix of intracranial arteries during aneurysm formation
  • may play an important role in the regulation of normal placentation by promoting the invasion of trophoblast cells into the uterine decidua
  • plays a crucial role in the regulation of early B lymphopoiesis
  • matricellular protein that is important for the regulation of cell growth and adhesion
  • stromal-derived matricellular protein SPARC is a novel regulator of islet survival and beta cell growth
  • CELLULAR PROCESS cell life, differentiation
    PHYSIOLOGICAL PROCESS
    text myogenesis, critical role in the morphological change of myoblasts
    PATHWAY
    metabolism
    signaling
    a component
  • component of the extracellular matrix
  • component of the ECM, impairing the proliferation of different cell types and modulatingtumor cell aggressive features
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • thrombospondin binding
  • binding to collagen (may include the regulation of collagen assembly, but sequestration or complexing with collagen may also modulate the many biological activities reported for SPARC)
  • interacting with PRKAA1 (SPARC may be involved in regulating glucose metabolism via PRKAA1 activation)
  • BID is putative cathepsin B target in SPARC-induced apoptosis
  • interacting with STAB1 (binding site on SPARC for STAB1)
  • interacting with TP53INP1 (decreases pancreatic cancer cell migration by regulating SPARC expression)
  • having a cell-autonomous survival activity, which requires AKT1-dependent regulation of TP53
  • SPARC induced G2/M cell cycle arrest was mediated through inhibition of the CCNB1-regulated signaling pathway involving CDKN1A and CDC2 expression
  • STAT3 plays a key role in SPARC induced G2/M arrest in medulloblastoma cells
  • is an effector of ITGB4-mediated invasion
  • STAB1, having the potential in inhibiting tumor growth by binding and internalizing secreted protein acidic and rich in cysteine (SPARC)
  • cell & other
  • modulating cell growth, attachment and migration of glioma cells in brain ECM
  • binds to several integral components of the ECM and exhibits an anti-adhesive function that includes abrogation of focal adhesions and disruption of cell spreading and motility
  • REGULATION
    activated by by insulin and leptin
    Other regulating dentin sialophosphoprotein in developing teeth
    ASSOCIATED DISORDERS
    corresponding disease(s) OIXVII
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    higher expression significantly associated with lymph node metastasis, lymphatic invasion and perineural invasion
    tumoral     --over  
    in hepatocellular carcinoma, and in in many advanced cancers, including malignant gliomas
    tumoral     --over  
    in osteosarcoma, and correlated with the worst event and relapse free survival
    tumoral     --over  
    is able to inhibit cell proliferation in medulloblastoma cell lines
    tumoral     --other  
    aberrant expression of SPARC associated with an invasive tumor cell phenotype and poor outcome in human melanomas
    constitutional       gain of function
    SPARC, MMP2 and MM9 were significantly up-regulated in intracranial aneurysms relative to the expression levels in the normal Circle of Willis arteries
    tumoral     --over  
    in endometrial cancer stem-like cells
    constitutional     --over  
    during skeletal muscle regeneration and inhibits myoblast differentiation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • prognostic marker for gastric cancer
  • Marker
    Therapy target
    SystemTypeDisorderPubmed
    respiratorylung 
    may represent a novel therapeutic target in idiopathic pulmonary fibrosis
    diabete  
    could be a convergence point for insulin and PRKAA1 signaling, making it an attractive molecule for prospective pharmacological or genetic manipulation
    cancerbrain 
    therapeutic candidate for medulloblastoma treatment
    cancerhemopathy 
    is a potential therapeutic target for AML
    ANIMAL & CELL MODELS
  • Sparc-null mice exhibit significantly more fat accumulation than wild-type mice
  • Sparc-null mice develop progressive osteoporosis, due to a defect in bone formation
  • Sparc-null mice have lower intraocular pressure (IOP)
  • Sparc-null mice had increased synaptic connections in the superior colliculus