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{{Infobox_gene}}
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{{Distinguish|Osteocalcin|Osteopontin}}
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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]].
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
Osteonectin is a [[glycoprotein]] in the [[bone]] that binds calcium. It is secreted by [[osteoblast]]s 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 [[Ampulla of Vater|ampullary]] cancers and chronic [[pancreatitis]] has been found.
{{GNF_Protein_box
| image = PBB_Protein_SPARC_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1bmo.
| PDB = {{PDB2|1bmo}}, {{PDB2|1nub}}, {{PDB2|1sra}}
| Name = Secreted protein, acidic, cysteine-rich (osteonectin)
| HGNCid = 11219
| Symbol = SPARC
| AltSymbols =; ON
| OMIM = 182120
| ECnumber = 
| Homologene = 31132
| MGIid = 98373
| GeneAtlas_image1 = PBB_GE_SPARC_200665_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_SPARC_212667_at_tn.png
| Function = {{GNF_GO|id=GO:0005507 |text = copper ion binding}} {{GNF_GO|id=GO:0005509 |text = calcium ion binding}} {{GNF_GO|id=GO:0005518 |text = collagen binding}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005604 |text = basement membrane}}
| Process = {{GNF_GO|id=GO:0001503 |text = ossification}} {{GNF_GO|id=GO:0007169 |text = transmembrane receptor protein tyrosine kinase signaling pathway}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 6678
    | Hs_Ensembl = ENSG00000113140
    | Hs_RefseqProtein = NP_003109
    | Hs_RefseqmRNA = NM_003118
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 5
    | Hs_GenLoc_start = 151021212
    | Hs_GenLoc_end = 151046710
    | Hs_Uniprot = P09486
    | Mm_EntrezGene = 20692
    | Mm_Ensembl = ENSMUSG00000018593
    | Mm_RefseqmRNA = XM_990025
    | Mm_RefseqProtein = XP_995119
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 55237924
    | Mm_GenLoc_end = 55263289
    | Mm_Uniprot = Q3TXI6
  }}
}}
'''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.  Some current research shows a correlation between osteonectin over expression and [[ampullary]] cancers and chronic pancreatitis.


==External links==
== Gene ==
* {{MeshName|Osteonectin}}
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 kD acidic and cysteine-rich glycoprotein consisting of a single polypeptide chain that can be broken into 4 domains: 1) a Ca<sup>++</sup> 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).<ref name="pmid2790009">{{cite journal | vauthors = Villarreal XC, Mann KG, Long GL | title = Structure of human osteonectin based upon analysis of cDNA and genomic sequences | journal = Biochemistry | volume = 28 | issue = 15 | pages = 6483–91 | date = Jul 1989 | pmid = 2790009 | doi = 10.1021/bi00441a049 }}</ref>
 
== Function ==
Osteonectin is an acidic [[extracellular matrix]] glycoprotein that plays a vital role in bone mineralization, [[Cell junction|cell-matrix]] interactions, and collagen binding. Osteonectin also increases the production and activity of [[matrix metalloproteinase]]s, a function important to invading cancer cells within bone. Additional functions of osteonectin beneficial to tumor cells include [[angiogenesis]], [[cell growth|proliferation]] and [[cell migration|migration]]. Overexpression of osteonectin is reported in many human cancers such as breast, prostate and colon.<ref name="pmid16041213">{{cite journal | vauthors = Guweidhi A, Kleeff J, Adwan H, Giese NA, Wente MN, Giese T, Büchler MW, Berger MR, Friess H | title = Osteonectin influences growth and invasion of pancreatic cancer cells | journal = Annals of Surgery | volume = 242 | issue = 2 | pages = 224–34 | date = Aug 2005 | pmid = 16041213 | pmc = 1357728 | doi = 10.1097/01.sla.0000171866.45848.68 }}</ref>
 
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.<ref name="pmid6380686">{{cite journal | vauthors = Wasi S, Otsuka K, Yao KL, Tung PS, Aubin JE, Sodek J, Termine JD | title = An osteonectinlike protein in porcine periodontal ligament and its synthesis by periodontal ligament fibroblasts | journal = Canadian Journal of Biochemistry and Cell Biology | volume = 62 | issue = 6 | pages = 470–8 | date = Jun 1984 | pmid = 6380686 | doi = 10.1139/o84-064 }}</ref> 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 thrombospondin and 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.<ref name="pmid1499220">{{cite journal | vauthors = Young MF, Kerr JM, Ibaraki K, Heegaard AM, Robey PG | title = Structure, expression, and regulation of the major noncollagenous matrix proteins of bone | journal = Clinical Orthopaedics and Related Research | volume =  | issue = 281 | pages = 275–94 | date = Aug 1992 | pmid = 1499220 | doi =  10.1097/00003086-199208000-00042}}</ref> Osteonectin has also been found to decrease DNA synthesis in cultured bone.<ref name="pmid8119487">{{cite journal | vauthors = Lane TF, Sage EH | title = The biology of SPARC, a protein that modulates cell-matrix interactions | journal = FASEB Journal | volume = 8 | issue = 2 | pages = 163–73 | date = Feb 1994 | pmid = 8119487 | doi =  }}</ref>
 
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).
 
==Model organisms==
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: right;" |
|+ ''Sparc'' knockout mouse phenotype
|-
! Characteristic!! Phenotype
|-
| [[Homozygote]] viability || bgcolor="#488ED3"|Normal
|-
| Homozygous Fertility || bgcolor="#488ED3"|Normal
|-
| Body weight || bgcolor="#488ED3"|Normal
|-
| [[Open Field (animal test)|Anxiety]] || bgcolor="#488ED3"|Normal
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
|-
| Grip strength || bgcolor="#488ED3"|Normal
|-
| [[Hot plate test|Hot plate]] || bgcolor="#488ED3"|Normal
|-
| [[Dysmorphology]] || bgcolor="#C40000"|Abnormal<ref name="Dysmorphology">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBAU/dysmorphology/ |title=Dysmorphology data for Sparc |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#C40000"|Abnormal<ref name="DEXA">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBAU/body-composition-dexa/ |title=DEXA data for Sparc |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Radiography]] || bgcolor="#C40000"|Abnormal<ref name="Radiography">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBAU/x-ray-imaging/ |title=Radiography data for Sparc |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| Body temperature || bgcolor="#488ED3"|Normal
|-
| Eye morphology || bgcolor="#C40000"|Abnormal<ref name="Eye morphology">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBAU/eye-morphology/ |title=Eye morphology data for Sparc |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
|-
| [[Blood plasma|Plasma]] [[immunoglobulin]]s || bgcolor="#488ED3"|Normal
|-
| [[Haematology]] || bgcolor="#488ED3"|Normal
|-
| [[Peripheral blood lymphocyte]]s || bgcolor="#488ED3"|Normal
|-
| [[Micronucleus test]] || bgcolor="#488ED3"|Normal
|-
| Heart weight || bgcolor="#488ED3"|Normal
|-
| Brain histopathology || bgcolor="#488ED3"|Normal
|-
| Eye Histopathology || bgcolor="#C40000"|Abnormal
|-
| MicroCT & Quantitative Faxitron || bgcolor="#C40000"|Abnormal
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Salmonella'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBAU/salmonella-challenge/ |title=''Salmonella'' infection data for Sparc |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| ''[[Citrobacter]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Citrobacter'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MBAU/citrobacter-challenge/ |title=''Citrobacter'' infection data for Sparc |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| colspan=2; style="text-align: center;" | All tests and analysis from<ref name="mgp_reference">{{cite journal | doi = 10.1111/j.1755-3768.2010.4142.x | title = The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice | year = 2010 | author = Gerdin AK | journal = Acta Ophthalmologica | volume = 88 | pages =  925–7 }}</ref><ref>[http://www.sanger.ac.uk/mouseportal/ Mouse Resources Portal], Wellcome Trust Sanger Institute.</ref>
|}
[[Model organism]]s have been used in the study of SPARC function. A conditional [[knockout mouse]] line, called ''Sparc<sup>tm1a(EUCOMM)Wtsi</sup>''<ref name="allele_ref">{{cite web |url=http://www.knockoutmouse.org/martsearch/search?query=Sparc |title=International Knockout Mouse Consortium}}</ref><ref name="mgi_allele_ref">{{cite web |url=http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4432869 |title=Mouse Genome Informatics}}</ref> was generated as part of the [[International Knockout Mouse Consortium]] program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.<ref name="pmid21677750">{{cite journal | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = Jun 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = Jun 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = Jan 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref>
 
Male and female animals underwent a standardized [[phenotypic screen]] to determine the effects of deletion.<ref name="mgp_reference" /><ref name="pmid21722353">{{cite journal | vauthors = van der Weyden L, White JK, Adams DJ, Logan DW | title = The mouse genetics toolkit: revealing function and mechanism | journal = Genome Biology | volume = 12 | issue = 6 | pages = 224 | year = 2011 | pmid = 21722353 | pmc = 3218837 | doi = 10.1186/gb-2011-12-6-224 }}</ref> Twenty six tests were carried out on [[mutant]] mice and six significant abnormalities were observed.<ref name="mgp_reference" /> Homozygous mutant animals had unusually white [[incisors]], decreased [[bone mineral]] density, abnormal [[lens (anatomy)|lens]] morphology, [[cataracts]] and a decreased length of long bones.<ref name="mgp_reference" />
 
== References ==
{{reflist|33em}}


==References==
== Further reading ==
{{reflist|2}}
{{refbegin|33em}}
==Further reading==
* {{cite journal | vauthors = Yan Q, Sage EH | title = SPARC, a matricellular glycoprotein with important biological functions | journal = The Journal of Histochemistry and Cytochemistry | volume = 47 | issue = 12 | pages = 1495–506 | date = Dec 1999 | pmid = 10567433 | doi = 10.1177/002215549904701201 }}
{{refbegin | 2}}
* {{cite journal | vauthors = Altura BM | title = Pharmacological effects of alpha-methyldopa, alpha-methylnorepinephrine, and octopamine on rat arteriolar, arterial, and terminal vascular smooth | journal = Circulation Research | volume = 36 | issue = 6 Suppl 1 | pages = 233–40 | date = Jun 1975 | pmid = 1093755 | doi = 10.1161/01.res.36.6.233 }}
{{PBB_Further_reading
* {{cite journal | vauthors = Raines EW, Lane TF, Iruela-Arispe ML, Ross R, Sage EH | title = The extracellular glycoprotein SPARC interacts with platelet-derived growth factor (PDGF)-AB and -BB and inhibits the binding of PDGF to its receptors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 4 | pages = 1281–5 | date = Feb 1992 | pmid = 1311092 | pmc = 48433 | doi = 10.1073/pnas.89.4.1281 }}
| citations =
* {{cite journal | vauthors = Mundlos S, Schwahn B, Reichert T, Zabel B | title = Distribution of osteonectin mRNA and protein during human embryonic and fetal development | journal = The Journal of Histochemistry and Cytochemistry | volume = 40 | issue = 2 | pages = 283–91 | date = Feb 1992 | pmid = 1552170 | doi = 10.1177/40.2.1552170 }}
*{{cite journal | author=Yan Q, Sage EH |title=SPARC, a matricellular glycoprotein with important biological functions. |journal=J. Histochem. Cytochem. |volume=47 |issue= 12 |pages= 1495-506 |year= 1999 |pmid= 10567433 |doi= }}
* {{cite journal | vauthors = Kelm RJ, Mann KG | title = Human platelet osteonectin: release, surface expression, and partial characterization | journal = Blood | volume = 75 | issue = 5 | pages = 1105–13 | date = Mar 1990 | pmid = 2306517 | doi =  }}
*{{cite journal | author=Altura BM |title=Pharmacological effects of alpha-methyldopa, alpha-methylnorepinephrine, and octopamine on rat arteriolar, arterial, and terminal vascular smooth. |journal=Circ. Res. |volume=36 |issue= 6 Suppl 1 |pages= 233-40 |year= 1975 |pmid= 1093755 |doi= }}
* {{cite journal | vauthors = Young MF, Day AA, Dominquez P, McQuillan CI, Fisher LW, Termine JD | title = Structure and expression of osteonectin mRNA in human tissue | journal = Connective Tissue Research | volume = 24 | issue = 1 | pages = 17–28 | year = 1990 | pmid = 2338025 | doi = 10.3109/03008209009152419 }}
*{{cite journal | author=Raines EW, Lane TF, Iruela-Arispe ML, ''et al.'' |title=The extracellular glycoprotein SPARC interacts with platelet-derived growth factor (PDGF)-AB and -BB and inhibits the binding of PDGF to its receptors. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue= 4 |pages= 1281-5 |year= 1992 |pmid= 1311092 |doi= }}
* {{cite journal | vauthors = Metsäranta M, Young MF, Sandberg M, Termine J, Vuorio E | title = Localization of osteonectin expression in human fetal skeletal tissues by in situ hybridization | journal = Calcified Tissue International | volume = 45 | issue = 3 | pages = 146–52 | date = Sep 1989 | pmid = 2505905 | doi = 10.1007/BF02556057 }}
*{{cite journal | author=Mundlos S, Schwahn B, Reichert T, Zabel B |title=Distribution of osteonectin mRNA and protein during human embryonic and fetal development. |journal=J. Histochem. Cytochem. |volume=40 |issue= 2 |pages= 283-91 |year= 1992 |pmid= 1552170 |doi= }}
* {{cite journal | vauthors = Sage H, Vernon RB, Funk SE, Everitt EA, Angello J | title = SPARC, a secreted protein associated with cellular proliferation, inhibits cell spreading in vitro and exhibits Ca+2-dependent binding to the extracellular matrix | journal = The Journal of Cell Biology | volume = 109 | issue = 1 | pages = 341–56 | date = Jul 1989 | pmid = 2745554 | pmc = 2115491 | doi = 10.1083/jcb.109.1.341 }}
*{{cite journal | author=Kelm RJ, Mann KG |title=Human platelet osteonectin: release, surface expression, and partial characterization. |journal=Blood |volume=75 |issue= 5 |pages= 1105-13 |year= 1990 |pmid= 2306517 |doi=  }}
* {{cite journal | vauthors = Swaroop A, Hogan BL, Francke U | title = Molecular analysis of the cDNA for human SPARC/osteonectin/BM-40: sequence, expression, and localization of the gene to chromosome 5q31-q33 | journal = Genomics | volume = 2 | issue = 1 | pages = 37–47 | date = Jan 1988 | pmid = 2838412 | doi = 10.1016/0888-7543(88)90107-3 }}
*{{cite journal | author=Young MF, Day AA, Dominquez P, ''et al.'' |title=Structure and expression of osteonectin mRNA in human tissue. |journal=Connect. Tissue Res. |volume=24 |issue= 1 |pages= 17-28 |year= 1990 |pmid= 2338025 |doi= }}
* {{cite journal | vauthors = Wewer UM, Albrechtsen R, Fisher LW, Young MF, Termine JD | title = Osteonectin/SPARC/BM-40 in human decidua and carcinoma, tissues characterized by de novo formation of basement membrane | journal = The American Journal of Pathology | volume = 132 | issue = 2 | pages = 345–55 | date = Aug 1988 | pmid = 3400777 | pmc = 1880722 | doi =  }}
*{{cite journal | author=Metsäranta M, Young MF, Sandberg M, ''et al.'' |title=Localization of osteonectin expression in human fetal skeletal tissues by in situ hybridization. |journal=Calcif. Tissue Int. |volume=45 |issue= 3 |pages= 146-52 |year= 1989 |pmid= 2505905 |doi= }}
* {{cite journal | vauthors = Clezardin P, Malaval L, Ehrensperger AS, Delmas PD, Dechavanne M, McGregor JL | title = Complex formation of human thrombospondin with osteonectin | journal = European Journal of Biochemistry / FEBS | volume = 175 | issue = 2 | pages = 275–84 | date = Aug 1988 | pmid = 3402455 | doi = 10.1111/j.1432-1033.1988.tb14194.x }}
*{{cite journal | author=Sage H, Vernon RB, Funk SE, ''et al.'' |title=SPARC, a secreted protein associated with cellular proliferation, inhibits cell spreading in vitro and exhibits Ca+2-dependent binding to the extracellular matrix. |journal=J. Cell Biol. |volume=109 |issue= 1 |pages= 341-56 |year= 1989 |pmid= 2745554 |doi= }}
* {{cite journal | vauthors = Lankat-Buttgereit B, Mann K, Deutzmann R, Timpl R, Krieg T | title = Cloning and complete amino acid sequences of human and murine basement membrane protein BM-40 (SPARC, osteonectin) | journal = FEBS Letters | volume = 236 | issue = 2 | pages = 352–6 | date = Aug 1988 | pmid = 3410046 | doi = 10.1016/0014-5793(88)80054-1 }}
*{{cite journal | author=Villarreal XC, Mann KG, Long GL |title=Structure of human osteonectin based upon analysis of cDNA and genomic sequences. |journal=Biochemistry |volume=28 |issue= 15 |pages= 6483-91 |year= 1989 |pmid= 2790009 |doi= }}
* {{cite journal | vauthors = Stenner DD, Tracy RP, Riggs BL, Mann KG | title = Human platelets contain and secrete osteonectin, a major protein of mineralized bone | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 83 | issue = 18 | pages = 6892–6 | date = Sep 1986 | pmid = 3489235 | pmc = 386616 | doi = 10.1073/pnas.83.18.6892 }}
*{{cite journal | author=Swaroop A, Hogan BL, Francke U |title=Molecular analysis of the cDNA for human SPARC/osteonectin/BM-40: sequence, expression, and localization of the gene to chromosome 5q31-q33. |journal=Genomics |volume=2 |issue= 1 |pages= 37-47 |year= 1988 |pmid= 2838412 |doi=  }}
* {{cite journal | vauthors = Jundt G, Berghäuser KH, Termine JD, Schulz A | title = Osteonectin--a differentiation marker of bone cells | journal = Cell and Tissue Research | volume = 248 | issue = 2 | pages = 409–15 | date = May 1987 | pmid = 3581152 | doi = 10.1007/bf00218209 }}
*{{cite journal | author=Wewer UM, Albrechtsen R, Fisher LW, ''et al.'' |title=Osteonectin/SPARC/BM-40 in human decidua and carcinoma, tissues characterized by de novo formation of basement membrane. |journal=Am. J. Pathol. |volume=132 |issue= 2 |pages= 345-55 |year= 1988 |pmid= 3400777 |doi= }}
* {{cite journal | vauthors = Fisher LW, Hawkins GR, Tuross N, Termine JD | title = Purification and partial characterization of small proteoglycans I and II, bone sialoproteins I and II, and osteonectin from the mineral compartment of developing human bone | journal = The Journal of Biological Chemistry | volume = 262 | issue = 20 | pages = 9702–8 | date = Jul 1987 | pmid = 3597437 | doi =  }}
*{{cite journal | author=Clezardin P, Malaval L, Ehrensperger AS, ''et al.'' |title=Complex formation of human thrombospondin with osteonectin. |journal=Eur. J. Biochem. |volume=175 |issue= 2 |pages= 275-84 |year= 1988 |pmid= 3402455 |doi= }}
* {{cite journal | vauthors = Sage H, Johnson C, Bornstein P | title = Characterization of a novel serum albumin-binding glycoprotein secreted by endothelial cells in culture | journal = The Journal of Biological Chemistry | volume = 259 | issue = 6 | pages = 3993–4007 | date = Mar 1984 | pmid = 6368555 | doi =  }}
*{{cite journal | author=Lankat-Buttgereit B, Mann K, Deutzmann R, ''et al.'' |title=Cloning and complete amino acid sequences of human and murine basement membrane protein BM-40 (SPARC, osteonectin). |journal=FEBS Lett. |volume=236 |issue= 2 |pages= 352-6 |year= 1988 |pmid= 3410046 |doi= }}
* {{cite journal | vauthors = Termine JD, Kleinman HK, Whitson SW, Conn KM, McGarvey ML, Martin GR | title = Osteonectin, a bone-specific protein linking mineral to collagen | journal = Cell | volume = 26 | issue = 1 Pt 1 | pages = 99–105 | date = Oct 1981 | pmid = 7034958 | doi = 10.1016/0092-8674(81)90037-4 }}
*{{cite journal | author=Stenner DD, Tracy RP, Riggs BL, Mann KG |title=Human platelets contain and secrete osteonectin, a major protein of mineralized bone. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=83 |issue= 18 |pages= 6892-6 |year= 1986 |pmid= 3489235 |doi= }}
* {{cite journal | vauthors = Xie RL, Long GL | title = Role of N-linked glycosylation in human osteonectin. Effect of carbohydrate removal by N-glycanase and site-directed mutagenesis on structure and binding of type V collagen | journal = The Journal of Biological Chemistry | volume = 270 | issue = 39 | pages = 23212–7 | date = Sep 1995 | pmid = 7559469 | doi = 10.1074/jbc.270.39.23212 }}
*{{cite journal | author=Jundt G, Berghäuser KH, Termine JD, Schulz A |title=Osteonectin--a differentiation marker of bone cells. |journal=Cell Tissue Res. |volume=248 |issue= 2 |pages= 409-15 |year= 1987 |pmid= 3581152 |doi=  }}
* {{cite journal | vauthors = Maurer P, Hohenadl C, Hohenester E, Göhring W, Timpl R, Engel J | title = The C-terminal portion of BM-40 (SPARC/osteonectin) is an autonomously folding and crystallisable domain that binds calcium and collagen IV | journal = Journal of Molecular Biology | volume = 253 | issue = 2 | pages = 347–57 | date = Oct 1995 | pmid = 7563094 | doi = 10.1006/jmbi.1995.0557 }}
*{{cite journal | author=Fisher LW, Hawkins GR, Tuross N, Termine JD |title=Purification and partial characterization of small proteoglycans I and II, bone sialoproteins I and II, and osteonectin from the mineral compartment of developing human bone. |journal=J. Biol. Chem. |volume=262 |issue= 20 |pages= 9702-8 |year= 1987 |pmid= 3597437 |doi=  }}
*{{cite journal | author=Sage H, Johnson C, Bornstein P |title=Characterization of a novel serum albumin-binding glycoprotein secreted by endothelial cells in culture. |journal=J. Biol. Chem. |volume=259 |issue= 6 |pages= 3993-4007 |year= 1984 |pmid= 6368555 |doi= }}
*{{cite journal | author=Termine JD, Kleinman HK, Whitson SW, ''et al.'' |title=Osteonectin, a bone-specific protein linking mineral to collagen. |journal=Cell |volume=26 |issue= 1 Pt 1 |pages= 99-105 |year= 1982 |pmid= 7034958 |doi= }}
*{{cite journal | author=Xie RL, Long GL |title=Role of N-linked glycosylation in human osteonectin. Effect of carbohydrate removal by N-glycanase and site-directed mutagenesis on structure and binding of type V collagen. |journal=J. Biol. Chem. |volume=270 |issue= 39 |pages= 23212-7 |year= 1995 |pmid= 7559469 |doi=  }}
*{{cite journal  | author=Maurer P, Hohenadl C, Hohenester E, ''et al.'' |title=The C-terminal portion of BM-40 (SPARC/osteonectin) is an autonomously folding and crystallisable domain that binds calcium and collagen IV. |journal=J. Mol. Biol. |volume=253 |issue= 2 |pages= 347-57 |year= 1995 |pmid= 7563094 |doi= 10.1006/jmbi.1995.0557 }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
== External links ==
* {{MeshName|Osteonectin}}
{{Antiangiogenics}}
{{PDB Gallery|geneid=6678}}
{{Calcium-binding proteins}}
{{Calcium-binding proteins}}
{{Glycoproteins}}
{{Glycoproteins}}
[[category:Glycoproteins]]
 
[[category:carbohydrates]]
[[Category:Glycoproteins]]
{{WikiDoc Sources}}
[[Category:Extracellular matrix proteins]]
[[Category:Matricellular proteins]]
[[Category:Genes mutated in mice]]

Latest revision as of 12:31, 4 November 2018

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SpeciesHumanMouse
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Not to be confused with Osteocalcin or Osteopontin.

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 kD acidic and cysteine-rich glycoprotein consisting of a single polypeptide chain that can be broken into 4 domains: 1) a Ca++ 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).[1]

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 and colon.[2]

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.[3] 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 thrombospondin and 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.[4] Osteonectin has also been found to decrease DNA synthesis in cultured bone.[5]

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).

Model organisms

Model organisms have been used in the study of SPARC function. A conditional knockout mouse line, called Sparctm1a(EUCOMM)Wtsi[14][15] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty six tests were carried out on mutant mice and six significant abnormalities were observed.[12] Homozygous mutant animals had unusually white incisors, decreased bone mineral density, abnormal lens morphology, cataracts and a decreased length of long bones.[12]

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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): 275–94. doi:10.1097/00003086-199208000-00042. PMID 1499220.
  5. ↑ Lane TF, Sage EH (Feb 1994). "The biology of SPARC, a protein that modulates cell-matrix interactions". FASEB Journal. 8 (2): 163–73. PMID 8119487.
  6. ↑ "Dysmorphology data for Sparc". Wellcome Trust Sanger Institute.
  7. ↑ "DEXA data for Sparc". Wellcome Trust Sanger Institute.
  8. ↑ "Radiography data for Sparc". Wellcome Trust Sanger Institute.
  9. ↑ "Eye morphology data for Sparc". Wellcome Trust Sanger Institute.
  10. ↑ "Salmonella infection data for Sparc". Wellcome Trust Sanger Institute.
  11. ↑ "Citrobacter infection data for Sparc". Wellcome Trust Sanger Institute.
  12. ↑ 12.0 12.1 12.2 12.3 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  13. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  14. ↑ "International Knockout Mouse Consortium".
  15. ↑ "Mouse Genome Informatics".
  16. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  17. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  18. ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  19. ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

External links

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