Osteonectin

SPARC
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1BMO, 1NUB, 1SRA, 2V53
Identifiers
Aliases	SPARC, BM-40, ON, OI17, secreted protein acidic and cysteine rich, ONT
External IDs	OMIM: 182120 MGI: 98373 HomoloGene: 31132 GeneCards: SPARC
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q33.1 Start 151,661,096 bp[1] End 151,686,975 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 B1.3|11 33.04 cM Start 55,285,326 bp[2] End 55,314,009 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tibia stromal cell of endometrium periodontal fiber gallbladder trigeminal ganglion olfactory bulb spinal ganglia visceral pleura smooth muscle tissue ascending aorta Top expressed in calvaria body of femur ascending aorta aortic valve belly cord carotid body molar vas deferens skin of abdomen skin of back More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium ion binding metal ion binding protein binding extracellular matrix binding collagen binding extracellular matrix structural constituent Cellular component cytoplasm platelet alpha granule endocytic vesicle lumen nuclear matrix plasma membrane intracellular anatomical structure basement membrane cell surface platelet alpha granule membrane mitochondrion platelet alpha granule lumen nucleus extracellular space vesicle extracellular region extracellular matrix synapse collagen-containing extracellular matrix glutamatergic synapse Biological process response to cytokine response to cadmium ion ossification lung development cellular response to growth factor stimulus response to peptide hormone platelet degranulation extracellular matrix organization response to L-ascorbic acid response to glucocorticoid wound healing receptor-mediated endocytosis negative regulation of endothelial cell proliferation positive regulation of endothelial cell migration response to calcium ion response to gravity heart development response to lipopolysaccharide response to lead ion regulation of cell population proliferation negative regulation of angiogenesis inner ear development regulation of cell morphogenesis response to cAMP response to ethanol bone development signal transduction pigmentation regulation of synapse organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6678 20692 Ensembl ENSG00000113140 ENSMUSG00000018593 UniProt P09486 P07214 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 Mb Chr 11: 55.29 – 55.31 Mb PubMed search [3] [4]
Wikidata
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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

Further reading

External links

• Osteonectin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)