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    SPARC secreted protein acidic and cysteine rich [ Homo sapiens (human) ]

    Gene ID: 6678, updated on 10-Dec-2024

    Summary

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    Official Symbol
    SPARCprovided by HGNC
    Official Full Name
    secreted protein acidic and cysteine richprovided by HGNC
    Primary source
    HGNC:HGNC:11219
    See related
    Ensembl:ENSG00000113140 MIM:182120; AllianceGenome:HGNC:11219
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ON; ONT; OI17; BM-40
    Summary
    This gene encodes a cysteine-rich acidic matrix-associated protein. The encoded protein is required for the collagen in bone to become calcified but is also involved in extracellular matrix synthesis and promotion of changes to cell shape. The gene product has been associated with tumor suppression but has also been correlated with metastasis based on changes to cell shape which can promote tumor cell invasion. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2015]
    Expression
    Broad expression in fat (RPKM 883.5), placenta (RPKM 823.4) and 20 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SPARC in Genome Data Viewer
    Location:
    5q33.1
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (151661096..151686915, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (152200073..152225896, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (151040657..151066476, complement)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene solute carrier family 36 member 1 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_82555 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_82563 Neighboring gene FAT atypical cadherin 2 Neighboring gene microRNA 6499 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23458 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:150950930-150951442 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:150974668-150975189 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:150998970-150999648 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:150999649-151000325 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr5:151003759-151004958 Neighboring gene uncharacterized LOC105378231 Neighboring gene uncharacterized LOC124901116 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23459 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23460 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr5:151042798-151043997 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr5:151063929-151064758 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:151065587-151066416 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:151066417-151067244 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:151079020-151079841 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16525 Neighboring gene colorectal liver metastasis associated transcript 3 Neighboring gene MPRA-validated peak5542 silencer Neighboring gene Sharpr-MPRA regulatory region 9564 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16526 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23461 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23462 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23463 Neighboring gene MPRA-validated peak5544 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23464 Neighboring gene MPRA-validated peak5543 silencer Neighboring gene RN7SK pseudogene 232 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr5:151109002-151109538 Neighboring gene Sharpr-MPRA regulatory region 608 Neighboring gene Sharpr-MPRA regulatory regions 4972 and 759 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr5:151124409-151125608 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23466 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23467 Neighboring gene ATOX1 antisense RNA 1 Neighboring gene antioxidant 1 copper chaperone

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. In vitro analyses of the anti-fibrotic effect of SPARC silencing in human Tenon's fibroblasts: comparisons with mitomycin C. Seet LF, et al. J Cell Mol Med, 2012 Jun. PMID 21801304, Free PMC Article
    2. Relationship and prognostic significance of SPARC and VEGF protein expression in colon cancer. Liang JF, et al. J Exp Clin Cancer Res, 2010 Jun 16. PMID 20565704, Free PMC Article
    3. Human retinal pigment epithelial SPARC expression and age: an immunohistochemical study. Howard C, et al. Histol Histopathol, 2010 Sep. PMID 20607658
    4. Evaluation of SPARC as a candidate gene of juvenile-onset primary open-angle glaucoma by mutation and copy number analyses. Chen LJ, et al. Mol Vis, 2010 Oct 8. PMID 21042566, Free PMC Article
    5. The stromal cell marker SPARC predicts for survival in patients with diffuse large B-cell lymphoma treated with rituximab. Meyer PN, et al. Am J Clin Pathol, 2011 Jan. PMID 21173124

    See all (388) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Downregulation of SPARC Expression Enhances the Fusion of BeWo Choriocarcinoma Cells.
      Title: Downregulation of SPARC Expression Enhances the Fusion of BeWo Choriocarcinoma Cells.
    2. Citric acid promotes SPARC release in pancreatic cancer cells and inhibits the progression of pancreatic tumors in mice on a high-fat diet.
      Title: Citric acid promotes SPARC release in pancreatic cancer cells and inhibits the progression of pancreatic tumors in mice on a high-fat diet.
    3. The role of SPARC (secreted protein acidic and rich in cysteine) in the pathogenesis of obesity, type 2 diabetes, and non-alcoholic fatty liver disease.
      Title: The role of SPARC (secreted protein acidic and rich in cysteine) in the pathogenesis of obesity, type 2 diabetes, and non-alcoholic fatty liver disease.
    4. Osteonectin (SPARC) prognostic value in prostate cancer.
      Title: Osteonectin (SPARC) prognostic value in prostate cancer.
    5. Immunohistochemical expression of SPARC in odontogenic keratocysts: a comparative study with other odontogenic cysts.
      Title: Immunohistochemical expression of SPARC in odontogenic keratocysts: a comparative study with other odontogenic cysts.
    6. The association of SPARC with hypertension and its function in endothelial-dependent relaxation.
      Title: The association of SPARC with hypertension and its function in endothelial-dependent relaxation.
    7. Peritumoral SPARC expression induced by exosomes from nasopharyngeal carcinoma infected Epstein-Barr virus: A poor prognostic marker.
      Title: Peritumoral SPARC expression induced by exosomes from nasopharyngeal carcinoma infected Epstein-Barr virus: A poor prognostic marker.
    8. Serum CRP interacts with SPARC and regulate immune response in severe cases of COVID-19 infection.
      Title: Serum CRP interacts with SPARC and regulate immune response in severe cases of COVID-19 infection.
    9. Novel pathogenic variants in SPARC as cause of osteogenesis imperfecta: Two case reports.
      Title: Novel pathogenic variants in SPARC as cause of osteogenesis imperfecta: Two case reports.
    10. Hepatic SPARC Expression Is Associated with Inflammasome Activation during the Progression of Non-Alcoholic Fatty Liver Disease in Both Mice and Morbidly Obese Patients.
      Title: Hepatic SPARC Expression Is Associated with Inflammasome Activation during the Progression of Non-Alcoholic Fatty Liver Disease in Both Mice and Morbidly Obese Patients.
    Submit: New GeneRIF Correction See all GeneRIFs (308)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Osteogenesis imperfecta type 17
    MedGen: C4225301 OMIM: 616507 GeneReviews: Not available
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calcium ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables calcium ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables collagen binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables collagen binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables extracellular matrix binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables extracellular matrix structural constituent RCA
    inferred from Reviewed Computational Analysis
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in negative regulation of angiogenesis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of endothelial cell proliferation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of endothelial cell migration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of cell morphogenesis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of synapse organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in semicircular canal morphogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in basement membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in collagen-containing extracellular matrix HDA PubMed 
    NOT located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endocytic vesicle lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular region HDA PubMed 
    located_in extracellular region NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    NOT located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nuclear matrix IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    NOT located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in platelet alpha granule IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in platelet alpha granule lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in platelet alpha granule membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    SPARC
    Names
    basement-membrane protein 40
    secreted protein, acidic, cysteine-rich (osteonectin)

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_042174.1 RefSeqGene

      Range
      5140..30959
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001309443.2 → NP_001296372.1  SPARC isoform 2 precursor

      See identical proteins and their annotated locations for NP_001296372.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice junction at the 5' end of an exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is 1 aa shorter compared to isoform 1.
      Source sequence(s)
      AL541830, BC072457, BI602719, BQ018477
      UniProtKB/TrEMBL
      B2RDL6
      Conserved Domains (2) summary
      cd01328
      Location:70 → 151
      FSL_SPARC; Follistatin-like SPARC (secreted protein, acidic, and rich in cysteines) domain; SPARC/BM-40/osteonectin is a multifunctional glycoprotein which modulates cellular interaction with the extracellular matrix by its binding to structural matrix proteins ...
      cd16231
      Location:154 → 293
      EFh_SPARC_like; EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich in cysteine (SPARC) and similar proteins

    2. NM_001309444.2 → NP_001296373.1  SPARC isoform 3 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate splice junction at the 5' end of the last exon compared to variant 1, that causes a frameshift. The resulting isoform (3) has a longer and distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC011374, AL540785, BC072457, BI602719, BQ018477
      UniProtKB/TrEMBL
      B2RDL6
      Conserved Domains (3) summary
      cd00252
      Location:154 → 290
      SPARC_EC; SPARC_EC; extracellular Ca2+ binding domain (containing 2 EF-hand motifs) of SPARC and related proteins (QR1, SC1/hevin, testican and tsc-36/FRP). SPARC (BM-40) is a multifunctional glycoprotein, a matricellular protein, that functions to regulate ...
      cd01328
      Location:71 → 152
      FSL_SPARC; Follistatin-like SPARC (secreted protein, acidic, and rich in cysteines) domain; SPARC/BM-40/osteonectin is a multifunctional glycoprotein which modulates cellular interaction with the extracellular matrix by its binding to structural matrix proteins ...
      pfam10591
      Location:153 → 287
      SPARC_Ca_bdg; Secreted protein acidic and rich in cysteine Ca binding region

    3. NM_003118.4 → NP_003109.1  SPARC isoform 1 precursor

      See identical proteins and their annotated locations for NP_003109.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the predominant isoform (1).
      Source sequence(s)
      BC072457, BQ018477
      Consensus CDS
      CCDS4318.1
      UniProtKB/Swiss-Prot
      D3DQH9, P09486, Q6IBK4
      UniProtKB/TrEMBL
      B2RDL6
      Related
      ENSP00000231061.4, ENST00000231061.9
      Conserved Domains (2) summary
      cd01328
      Location:71 → 152
      FSL_SPARC; Follistatin-like SPARC (secreted protein, acidic, and rich in cysteines) domain; SPARC/BM-40/osteonectin is a multifunctional glycoprotein which modulates cellular interaction with the extracellular matrix by its binding to structural matrix proteins ...
      cd16231
      Location:155 → 294
      EFh_SPARC_like; EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich in cysteine (SPARC) and similar proteins

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      151661096..151686915 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      152200073..152225896 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P09486.1 GenPept UniProtKB/Swiss-Prot:P09486

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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