SPARC
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSPARC, BM-40, ON, OI17, secreted protein acidic and cysteine rich, ONT
External IDsOMIM: 182120 MGI: 98373 HomoloGene: 31132 GeneCards: SPARC
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003118
NM_001309443
NM_001309444

NM_009242
NM_001290817

RefSeq (protein)

NP_001296372
NP_001296373
NP_003109

NP_001277746
NP_033268

Location (UCSC)Chr 5: 151.66 – 151.69 MbChr 11: 55.29 – 55.31 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Osteonectin (ON) also known as secreted protein acidic and rich in cysteine (SPARC) or basement-membrane protein 40 (BM-40) is a protein that in humans is encoded by the SPARC gene.

Osteonectin is a glycoprotein in the bone that binds calcium. It is secreted by osteoblasts during bone formation, initiating mineralization and promoting mineral crystal formation. Osteonectin also shows affinity for collagen in addition to bone mineral calcium. A correlation between osteonectin over-expression and ampullary cancers and chronic pancreatitis has been found.

Gene

The human SPARC gene is 26.5 kb long, and contains 10 exons and 9 introns and is located on chromosome 5q31-q33.

Structure

Osteonectin is a 40 kDa acidic and cysteine-rich glycoprotein consisting of a single polypeptide chain that can be broken into 4 domains: 1) a Ca2+ binding domain near the glutamic acid-rich region at the amino terminus (domain I), 2) a cysteine-rich domain (II), 3) a hydrophilic region (domain III), and 4) an EF hand motif at the carboxy terminus region (domain IV).[5]

Function

Osteonectin is an acidic extracellular matrix glycoprotein that plays a vital role in bone mineralization, cell-matrix interactions, and collagen binding. Osteonectin also increases the production and activity of matrix metalloproteinases, a function important to invading cancer cells within bone. Additional functions of osteonectin beneficial to tumor cells include angiogenesis, proliferation and migration. Overexpression of osteonectin is reported in many human cancers such as breast, prostate, colon and pancreatic.[6]

This molecule has been implicated in several biological functions, including mineralization of bone and cartilage, inhibiting mineralization, modulation of cell proliferation, facilitation of acquisition of differentiated phenotype and promotion of cell attachment and spreading.

A number of phosphoproteins and glycoproteins are found in bone. The phosphate is bound to the protein backbone through phosphorylated serine or threonine amino acid residues. The best characterized of these bone proteins is osteonectin. It binds collagen and hydroxyapatite in separate domains, is found in relatively large amounts in immature bone, and promotes mineralization of collagen.

Tissue distribution

Fibroblasts, including periodontal fibroblasts, synthesize osteonectin.[7] This protein is synthesized by macrophages at sites of wound repair and platelet degranulation, so it may play an important role in wound healing. SPARC does not support cell attachment, and like tenascin, is anti-adhesive and an inhibitor of cell spreading. It disrupts focal adhesions in fibroblasts. It also regulates the proliferation of some cells, especially endothelial cells, mediated by its ability to bind to cytokines and growth factors.[8] Osteonectin has also been found to decrease DNA synthesis in cultured bone.[9]

High levels of immunodetectable osteonectin are found in active osteoblasts and marrow progenitor cells, odontoblasts, periodontal ligament and gingival cells, and some chondrocytes and hypertrophic chondrocytes. Osteonectin is also detectable in osteoid, bone matrix proper, and dentin. Osteonectin has been localized in a variety of tissues, but is found in greatest abundance in osseous tissue, tissues characterized by high turnover (such as intestinal epithelium), basement membranes, and certain neoplasms. Osteonectin is expressed by a wide variety of cells, including chondrocytes, fibroblasts, platelets, endothelial cells, epithelial cells, Leydig cells, Sertoli cells, luteal cells, adrenal cortical cells, and numerous neoplastic cell lines (such as SaOS-2 cells from human osteosarcoma).

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000113140Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000018593Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Villarreal XC, Mann KG, Long GL (Jul 1989). "Structure of human osteonectin based upon analysis of cDNA and genomic sequences". Biochemistry. 28 (15): 6483–91. doi:10.1021/bi00441a049. PMID 2790009.
  6. ^ Guweidhi A, Kleeff J, Adwan H, Giese NA, Wente MN, Giese T, Büchler MW, Berger MR, Friess H (Aug 2005). "Osteonectin influences growth and invasion of pancreatic cancer cells". Annals of Surgery. 242 (2): 224–34. doi:10.1097/01.sla.0000171866.45848.68. PMC 1357728. PMID 16041213.
  7. ^ Wasi S, Otsuka K, Yao KL, Tung PS, Aubin JE, Sodek J, Termine JD (Jun 1984). "An osteonectinlike protein in porcine periodontal ligament and its synthesis by periodontal ligament fibroblasts". Canadian Journal of Biochemistry and Cell Biology. 62 (6): 470–8. doi:10.1139/o84-064. PMID 6380686.
  8. ^ Young MF, Kerr JM, Ibaraki K, Heegaard AM, Robey PG (Aug 1992). "Structure, expression, and regulation of the major noncollagenous matrix proteins of bone". Clinical Orthopaedics and Related Research. 281 (281): 275–94. doi:10.1097/00003086-199208000-00042. PMID 1499220.
  9. ^ Lane TF, Sage EH (Feb 1994). "The biology of SPARC, a protein that modulates cell-matrix interactions". FASEB Journal. 8 (2): 163–73. doi:10.1096/fasebj.8.2.8119487. PMID 8119487. S2CID 32958146.

Further reading