Browse SPARC

Summary
SymbolSPARC
Namesecreted protein, acidic, cysteine-rich (osteonectin)
Aliases cysteine-rich protein; osteonectin; ON; BM-40; basement-membrane protein 40; Secreted protein acidic and ric ......
Chromosomal Location5q31-q33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Secreted, extracellular space, extracellular matrix, basement membrane Note=In or around the basement membrane.
Domain PF09289 Follistatin/Osteonectin-like EGF domain
PF00050 Kazal-type serine protease inhibitor domain
PF10591 Secreted protein acidic and rich in cysteine Ca binding region
Function

Appears to regulate cell growth through interactions with the extracellular matrix and cytokines. Binds calcium and copper, several types of collagen, albumin, thrombospondin, PDGF and cell membranes. There are two calcium binding sites; an acidic domain that binds 5 to 8 Ca(2+) with a low affinity and an EF-hand loop that binds a Ca(2+) ion with a high affinity.

> Gene Ontology
 
Biological Process GO:0001101 response to acid chemical
GO:0001501 skeletal system development
GO:0001503 ossification
GO:0001525 angiogenesis
GO:0001667 ameboidal-type cell migration
GO:0001935 endothelial cell proliferation
GO:0001936 regulation of endothelial cell proliferation
GO:0001937 negative regulation of endothelial cell proliferation
GO:0002237 response to molecule of bacterial origin
GO:0002576 platelet degranulation
GO:0006887 exocytosis
GO:0006898 receptor-mediated endocytosis
GO:0007423 sensory organ development
GO:0007507 heart development
GO:0007584 response to nutrient
GO:0009629 response to gravity
GO:0009743 response to carbohydrate
GO:0009991 response to extracellular stimulus
GO:0010035 response to inorganic substance
GO:0010038 response to metal ion
GO:0010288 response to lead ion
GO:0010594 regulation of endothelial cell migration
GO:0010595 positive regulation of endothelial cell migration
GO:0010631 epithelial cell migration
GO:0010632 regulation of epithelial cell migration
GO:0010634 positive regulation of epithelial cell migration
GO:0014074 response to purine-containing compound
GO:0016525 negative regulation of angiogenesis
GO:0022604 regulation of cell morphogenesis
GO:0030198 extracellular matrix organization
GO:0030323 respiratory tube development
GO:0030324 lung development
GO:0030335 positive regulation of cell migration
GO:0031667 response to nutrient levels
GO:0031960 response to corticosteroid
GO:0032496 response to lipopolysaccharide
GO:0033273 response to vitamin
GO:0033591 response to L-ascorbic acid
GO:0034284 response to monosaccharide
GO:0040017 positive regulation of locomotion
GO:0043062 extracellular structure organization
GO:0043434 response to peptide hormone
GO:0043542 endothelial cell migration
GO:0043583 ear development
GO:0045055 regulated exocytosis
GO:0045471 response to ethanol
GO:0045765 regulation of angiogenesis
GO:0046683 response to organophosphorus
GO:0046686 response to cadmium ion
GO:0048514 blood vessel morphogenesis
GO:0048545 response to steroid hormone
GO:0048839 inner ear development
GO:0050673 epithelial cell proliferation
GO:0050678 regulation of epithelial cell proliferation
GO:0050680 negative regulation of epithelial cell proliferation
GO:0051272 positive regulation of cellular component movement
GO:0051384 response to glucocorticoid
GO:0051591 response to cAMP
GO:0051592 response to calcium ion
GO:0060348 bone development
GO:0060541 respiratory system development
GO:0090130 tissue migration
GO:0090132 epithelium migration
GO:0097305 response to alcohol
GO:1901342 regulation of vasculature development
GO:1901343 negative regulation of vasculature development
GO:1901652 response to peptide
GO:2000147 positive regulation of cell motility
GO:2000181 negative regulation of blood vessel morphogenesis
Molecular Function GO:0005518 collagen binding
GO:0050840 extracellular matrix binding
Cellular Component GO:0005578 proteinaceous extracellular matrix
GO:0005604 basement membrane
GO:0016363 nuclear matrix
GO:0030139 endocytic vesicle
GO:0030141 secretory granule
GO:0030659 cytoplasmic vesicle membrane
GO:0030667 secretory granule membrane
GO:0031091 platelet alpha granule
GO:0031092 platelet alpha granule membrane
GO:0031093 platelet alpha granule lumen
GO:0031983 vesicle lumen
GO:0034399 nuclear periphery
GO:0034774 secretory granule lumen
GO:0044420 extracellular matrix component
GO:0060205 cytoplasmic membrane-bounded vesicle lumen
GO:0071682 endocytic vesicle lumen
GO:0099503 secretory vesicle
> KEGG and Reactome Pathway
 
KEGG -
Reactome R-HSA-2173782: Binding and Uptake of Ligands by Scavenger Receptors
R-HSA-3000178: ECM proteoglycans
R-HSA-1474244: Extracellular matrix organization
R-HSA-109582: Hemostasis
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-114608: Platelet degranulation
R-HSA-76005: Response to elevated platelet cytosolic Ca2+
R-HSA-3000497: Scavenging by Class H Receptors
R-HSA-5653656: Vesicle-mediated transport
Summary
SymbolSPARC
Namesecreted protein, acidic, cysteine-rich (osteonectin)
Aliases cysteine-rich protein; osteonectin; ON; BM-40; basement-membrane protein 40; Secreted protein acidic and ric ......
Chromosomal Location5q31-q33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between SPARC and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between SPARC and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
20063317Gastric Carcinoma; Pancreatic Carcinoma; Colorectal CarcinomaInhibit immunityIdentification of SPARC as a candidate target antigen for immunotherapy of various cancers. A genome-wide cDNA microarray analysis identified that secreted protein acidic and rich in cysteine (SPARC) gene is overexpressed in the gastric, pancreatic and colorectal cancer tissues but not in their noncancerous counterparts. The SPARC-A24-1(143-151) (DYIGPCKYI) and SPARC-A24-4(225-234) (MYIFPVHWQF) peptides-reactive CTLs were successfully induced from peripheral blood mononuclear cells by in vitro stimulation with these two peptides in HLA-A24 (A*2402) positive healthy donors and cancer patients, and these CTLs exhibited cytotoxicity specific to cancer cells expressing both SPARC and HLA-A24 (A*2402).
15958556MelanomaInhibit immunityIn the present study, we show that SPARC produced by melanoma cells modulates the antitumor activity of polymorphonuclear leukocytes (PMN). In addition, SPARC-sup cells stimulated the in vitro migration and triggered the antimelanoma cytotoxic capacity of human PMN, an effect that was reverted in the presence of SPARC purified from melanoma cells or by reexpressing SPARC in SPARC-sup cells.
18974151Breast CarcinomaInhibit immunityGene expression profiles associate SPARC to malignant progression. Using reciprocal bone marrow chimeras between SPARC knockout and wild-type mice, we show that SPARC produced by inflammatory cells is necessary for spontaneous, but not experimental, i.v. metastasis. Macrophage-derived SPARC induces cancer cell migration and enhances their migration to other ECM proteins at least through alpha(v)beta(5) integrin.
Summary
SymbolSPARC
Namesecreted protein, acidic, cysteine-rich (osteonectin)
Aliases cysteine-rich protein; osteonectin; ON; BM-40; basement-membrane protein 40; Secreted protein acidic and ric ......
Chromosomal Location5q31-q33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of SPARC in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolSPARC
Namesecreted protein, acidic, cysteine-rich (osteonectin)
Aliases cysteine-rich protein; osteonectin; ON; BM-40; basement-membrane protein 40; Secreted protein acidic and ric ......
Chromosomal Location5q31-q33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of SPARC in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.7430.0636
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.9360.827
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.5930.843
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.7660.149
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-1.1170.701
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.3150.936
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.1070.884
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.6470.824
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.4540.89
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.4550.661
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 283.2340.505
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.2450.162
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of SPARC in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolSPARC
Namesecreted protein, acidic, cysteine-rich (osteonectin)
Aliases cysteine-rich protein; osteonectin; ON; BM-40; basement-membrane protein 40; Secreted protein acidic and ric ......
Chromosomal Location5q31-q33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SPARC. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolSPARC
Namesecreted protein, acidic, cysteine-rich (osteonectin)
Aliases cysteine-rich protein; osteonectin; ON; BM-40; basement-membrane protein 40; Secreted protein acidic and ric ......
Chromosomal Location5q31-q33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SPARC. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SPARC.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolSPARC
Namesecreted protein, acidic, cysteine-rich (osteonectin)
Aliases cysteine-rich protein; osteonectin; ON; BM-40; basement-membrane protein 40; Secreted protein acidic and ric ......
Chromosomal Location5q31-q33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SPARC. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolSPARC
Namesecreted protein, acidic, cysteine-rich (osteonectin)
Aliases cysteine-rich protein; osteonectin; ON; BM-40; basement-membrane protein 40; Secreted protein acidic and ric ......
Chromosomal Location5q31-q33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of SPARC expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolSPARC
Namesecreted protein, acidic, cysteine-rich (osteonectin)
Aliases cysteine-rich protein; osteonectin; ON; BM-40; basement-membrane protein 40; Secreted protein acidic and ric ......
Chromosomal Location5q31-q33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between SPARC and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolSPARC
Namesecreted protein, acidic, cysteine-rich (osteonectin)
Aliases cysteine-rich protein; osteonectin; ON; BM-40; basement-membrane protein 40; Secreted protein acidic and ric ......
Chromosomal Location5q31-q33
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting SPARC collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting SPARC.
ID Name Drug Type Targets #Targets
DB11093Calcium CitrateSmall MoleculeCADPS, CADPS2, CALB2, CALR, CALR3, CANX, CAPS, CASQ1, CASQ2, CASR, ......29
DB11348Calcium PhosphateSmall MoleculeCADPS, CADPS2, CALB2, CALR, CALR3, CANX, CAPS, CASQ1, CASQ2, CASR, ......29