Bone sialoprotein

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Integrin-binding sialoprotein
Bone Sialoprotein Model.png
Model of human bone sialoprotein. The protein backbone is shown in orange; most of the protein is in the form of a random globule, with a surface layer of glycans (shown in red). The globule is thought to nucleate crystallization of hydroxyapatite, which is the mineral part of bone. A negatively charged region of the globule attracts calcium ions (shown as green spheres), beginning the crystallization process. The unwound protein strand on the right of the picture is thought to anchor the protein to the cell surface, before it is transferred to the collagen fibrils that provide the main organic component of bone[1].
External IDs OMIM147563 MGI96389 HomoloGene3644 GeneCards: IBSP Gene
Species Human Mouse
Entrez 3381 15891
Ensembl ENSG00000029559 ENSMUSG00000029306
UniProt P21815 Q61711
RefSeq (mRNA) NM_004967 NM_008318
RefSeq (protein) NP_004958 NP_032344
Location (UCSC) Chr 4:
88.72 – 88.73 Mb
Chr 5:
104.3 – 104.31 Mb
PubMed search [1] [2]

Bone sialoprotein (BSP) is a component of mineralized tissues such as bone, dentin, cementum and calcified cartilage. BSP is a significant component of the bone extracellular matrix and has been suggested to constitute approximately 8% of all non-collagenous proteins found in bone and cementum.[2] BSP, a SIBLING protein, was originally isolated from bovine cortical bone as a 23-kDa glycopeptide with high sialic acid content.[3][4]

The human variant of BSP is called bone sialoprotein 2 also known as cell-binding sialoprotein or integrin-binding sialoprotein and is encoded by the IBSP gene.[5]


Native BSP has an apparent molecular weight of 60-80 kDa based on SDS-PAGE, which is a considerable deviation from the predicted weight (based on cDNA sequence) of approximately 33 kDa.[6] The mammalian BSP cDNAs encode for proteins averaging 327 amino acids, which includes the 16-residue preprotein secretory signal peptide. Among the mammalian cDNAs currently characterized, there is an approximate 45% conservation of sequence identity and a further 10-23% conservative substitution. The protein is highly acidic (pKa of ~ 3.9)[7] and contains a large amount of Glu residues, constituting ~22% of the total amino acid.

Secondary structure prediction and hydrophobicity analyses suggest that the primary sequence of BSP has an open, flexible structure with the potential to form regions of α-helix and some β-sheet.[8] However, the majority of studies have demonstrated that BSP has no α-helical or β-sheet structure by 1D NMR[7][9] and circular dichroism.[10] Analysis of native protein by electron microscopy confirm that the protein has an extended structure approximately 40 nm in length.[11] This flexible conformation suggests that the protein has few structural domains, however it has been suggested that there may be several spatially segmented functional domains including a hydrophobic collagen-binding domain (rattus norvegicus residues 36-57),[12] a hydroxyapatite-nucleating region of contiguous glutamic acid residues (rattus norvegicus residues 78-85, 155-164)[10] and a classical integrin-binding motif (RGD) near the C-terminal (rattus norvegicus residues 288-291).

BSP has been demonstrated to be extensively post-translationally modified, with carbohydrates and other modifications comprising approximately 50% of the molecular weight of the native protein.[13][14] These modifications, which include N- and O-linked glycosylation, tyrosine sulfation and serine and threonine phosphorylation, make the protein highly heterogeneous.


The amount of BSP in bone and dentin is roughly equal,[15] however the function of BSP in these mineralized tissues is not known. One possibility is that BSP acts as a nucleus for the formation of the first apatite crystals.[16] As the apatite forms along the collagen fibres within the extracellular matrix, BSP could then help direct, redirect or inhibit the crystal growth.

Additional roles of BSP are MMP-2 activation, angiogenesis, and protection from complement-mediated cell lysis. Regulation of the BSP gene is important to bone matrix mineralization and tumor growth in bone.[17]


  1. ^ Vincent, K.; Durrant, M.C. (2013). "A structural and functional model for human bone sialoprotein". Journal of Molecular Graphics and Modelling 39: 108–117. doi:10.1016/j.jmgm.2012.10.007. 
  2. ^ Fisher LW, McBride OW, Termine JD, Young MF (February 1990). "Human bone sialoprotein. Deduced protein sequence and chromosomal localization". J. Biol. Chem. 265 (4): 2347–51. PMID 2404984. 
  3. ^ Williams PA, Peacocke AR (November 1965). "The physical properties of a glycoprotein from bovine cortical bone (bone sialoprotein)". Biochim. Biophys. Acta 101 (3): 327–35. doi:10.1016/0926-6534(65)90011-4. PMID 5862222. 
  4. ^ Herring GM (February 1964). "Comparison of bovine bone sialoprotein and serum orosomucoid". Nature 201 (4920): 709. doi:10.1038/201709a0. PMID 14139700. 
  5. ^ Kerr JM, Fisher LW, Termine JD, Wang MG, McBride OW, Young MF (August 1993). "The human bone sialoprotein gene (IBSP): genomic localization and characterization". Genomics 17 (2): 408–15. doi:10.1006/geno.1993.1340. PMID 8406493. 
  6. ^ Fisher LW, Whitson SW, Avioli LV, Termine JD (October 1983). "Matrix sialoprotein of developing bone". J. Biol. Chem. 258 (20): 12723–7. PMID 6355090. 
  7. ^ a b Stubbs JT, Mintz KP, Eanes ED, Torchia DA, Fisher LW (August 1997). "Characterization of native and recombinant bone sialoprotein: delineation of the mineral-binding and cell adhesion domains and structural analysis of the RGD domain". J. Bone Miner. Res. 12 (8): 1210–22. doi:10.1359/jbmr.1997.12.8.1210. PMID 9258751. 
  8. ^ Shapiro HS, Chen J, Wrana JL, Zhang Q, Blum M, Sodek J (November 1993). "Characterization of porcine bone sialoprotein: primary structure and cellular expression". Matrix 13 (6): 431–40. doi:10.1016/s0934-8832(11)80109-5. PMID 8309422. 
  9. ^ Fisher LW, Torchia DA, Fohr B, Young MF, Fedarko NS (January 2001). "Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin". Biochem. Biophys. Res. Commun. 280 (2): 460–5. doi:10.1006/bbrc.2000.4146. PMID 11162539. 
  10. ^ a b Tye CE, Rattray KR, Warner KJ, Gordon JA, Sodek J, Hunter GK, Goldberg HA (March 2003). "Delineation of the hydroxyapatite-nucleating domains of bone sialoprotein". J. Biol. Chem. 278 (10): 7949–55. doi:10.1074/jbc.M211915200. PMID 12493752. 
  11. ^ Oldberg A, Franzén A, Heinegård D (December 1988). "The primary structure of a cell-binding bone sialoprotein". J. Biol. Chem. 263 (36): 19430–2. PMID 3198635. 
  12. ^ Tye CE, Hunter GK, Goldberg HA (April 2005). "Identification of the type I collagen-binding domain of bone sialoprotein and characterization of the mechanism of interaction". J. Biol. Chem. 280 (14): 13487–92. doi:10.1074/jbc.M408923200. PMID 15703183. 
  13. ^ Kinne RW, Fisher LW (July 1987). "Keratan sulfate proteoglycan in rabbit compact bone is bone sialoprotein II". J. Biol. Chem. 262 (21): 10206–11. PMID 2956253. 
  14. ^ Ganss B, Kim RH, Sodek J (1999). "Bone sialoprotein". Crit. Rev. Oral Biol. Med. 10 (1): 79–98. doi:10.1177/10454411990100010401. PMID 10759428. 
  15. ^ Qin C, Brunn JC, Jones J, George A, Ramachandran A, Gorski JP, Butler WT (April 2001). "A comparative study of sialic acid-rich proteins in rat bone and dentin". Eur. J. Oral Sci. 109 (2): 133–41. doi:10.1034/j.1600-0722.2001.00001.x. PMID 11347657. 
  16. ^ Hunter GK, Goldberg HA (August 1994). "Modulation of crystal formation by bone phosphoproteins: role of glutamic acid-rich sequences in the nucleation of hydroxyapatite by bone sialoprotein". Biochem. J. 302 ( Pt 1) (Pt 1): 175–9. PMC 1137206. PMID 7915111. 
  17. ^ Ogata Y (April 2008). "Bone sialoprotein and its transcriptional regulatory mechanism". J. Periodont. Res. 43 (2): 127–35. doi:10.1111/j.1600-0765.2007.01014.x. PMID 18302613. 

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