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FLASH GENE
Symbol SPARC contributors: mct - updated : 02-07-2017
HGNC name secreted protein, acidic, cysteine-rich (osteonectin)
HGNC id 11219
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)
  • SPARC promoted glucose-stimulated insulin secretion (GSIS) by inhibiting RGS4 in pancreatic beta cells
  • 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