IBSP

Official Full Name

integrin binding sialoprotein

Organism

Homo sapiens

GeneID

3381

Background

The protein encoded by this gene is a major structural protein of the bone matrix. It constitutes approximately 12% of the noncollagenous proteins in human bone and is synthesized by skeletal-associated cell types, including hypertrophic chondrocytes, osteoblasts, osteocytes, and osteoclasts. The only extraskeletal site of its synthesis is the trophoblast. This protein binds to calcium and hydroxyapatite via its acidic amino acid clusters, and mediates cell attachment through an RGD sequence that recognizes the vitronectin receptor. [provided by RefSeq, Jul 2008]

Synonyms

BSP; BNSP; SP-II; BSP-II;

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Detailed Information

Overview

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. Bone sialoprotein (BSP) is a component of mineralized tissues such as bone, dentin, cementum, and calcified cartilage. BSP, a SIBLING protein, was originally isolated from bovine cortical bone as a 23-kDa glycopeptide with high sialic acid content. 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. It constitutes approximately 12% of the non-collagenous proteins in human bone and is synthesized by skeletal-associated cell types, including hypertrophic chondrocytes, osteoblasts, osteocytes, and osteoclasts. The only extraskeletal site of its synthesis is the trophoblast. This protein binds to calcium and hydroxyapatite via its acidic amino acid clusters, and mediates cell attachment through an RGD sequence that recognizes the vitronectin receptor.

IBSP Figure 1. The 3D structure of P2RX2.
(https://en. wikipedia. org/wiki/File:Bone_Sialoprotein_Model. png)

Structure:

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. The mammalian BSP cDNAs encode for proteins averaging 317 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) and contains a large amount of Glu residues, constituting ~22% of the total amino acid.

Secondary structure prediction and hydrophobic analysis indicated that the main sequence of BSP has an open, flexible and potential structure-forming region of as-helix and some isome-sheet. However, most studies have proved that BSP does not have the 1-helical or application-sheet structure 1 d NMR and circular dichroism. Analysis of natural protein by electron microscopy confirmed that this protein has an extended structure of about 40nm.

BSP has been shown to be an extensive post-translational modification, with carbohydrates and other modifications accounting for about 50% of the molecular weight of natural proteins. These modifications, including N- and O-linked glycosylation, tyrosine sulfonation, serine and threonine phosphorylation, making the protein highly heterogeneous. A three-dimensional model of human bone saliva protein was established using molecular modeling techniques, as shown in the figure. The model suggests that the protein provides a flexible template for the rapid self-assembly of calcium and phosphate ions, thus enabling the growth and nucleation of hydroxyapatite crystals.

Functions:

BSP content in bone and dentin is approximately equal, but the role of BSP in these mineralized tissues is not clear. One possibility is that BSP formed as the first apatite crystal. When apatite forms along collagen fibers in the extracellular matrix, BSP can help guide, redirect, or inhibit crystal growth. Other roles of BSP are angiogenesis and prevention of complementary-mediated cell lysis.

Role in disease:

Bone sialoprotein (BSP) has been involved in a variety of physiological and pathological events, including tumor cell invasion, bone reposition, adhesion, and matrix degradation. In order to explore the potential role of BSP in human breast cancer cell invasion and metastasis, anti-retroviral mediated RNAi was used to deplete the BSP level in breast cancer cell line mda-mb-231bo (231bo-bsp27), and cell clones of 231bo-bsp27 and 231bo-bsp81 were established. The proliferation of these cells, colony formation, and the ability to invade the matrix were all reduced by the clonal delection of BSP. Both 231bo-bsp27 cells and 231bo-bsp81 cells showed a significant decrease in intracardiac injection of bone metastatic potential (15. 4% and 28. 6%, respectively) after X-ray detection. In addition, the expression of the integrin-3 protein and the inactivated 3 decreased BSP-silenced cells, while the expression of heterotopic BSP increased the levels of the integrin-3 and inactivated-3. Together, these results showed that BSP silencing reduced the levels of the integrin-3 and inactivated-3, thereby inhibiting cell migration and invasion and reducing the ability of cells to migrate to bone.

References:

Kerr JM, Fisher LW, Termine JD, Wang MG, McBride OW, Young MF (1993). "The human bone sialoprotein gene (IBSP): genomic localization and characterization." Genomics. 17 (2): 408-15.
Herring GM (1964). "Comparison of bovine bone sialoprotein and serum orosomucoid." Nature. 201 (4920): 709.
Fisher LW, McBride OW, Termine JD, Young MF (1990). "Human bone sialoprotein. Deduced protein sequence and chromosomal localization." J. Biol. Chem. 265 (4): 2347-51.
Fisher LW, Whitson SW, Avioli LV, Termine JD (1983). "Matrix sialoprotein of developing bone." J. Biol. Chem. 258 (20): 12723-7.
Stubbs JT, Mintz KP, Eanes ED, Torchia DA, Fisher LW (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.
Shapiro HS, Chen J, Wrana JL, Zhang Q, Blum M, Sodek J (1993). "Characterization of porcine bone sialoprotein: primary structure and cellular expression." Matrix. 13 (6): 431-40.
Fisher LW, Torchia DA, Fohr B, Young MF, Fedarko NS (2001). "Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin." Biochem. Biophys. Res. Commun. 280 (2): 460-5.
Tye CE, Rattray KR, Warner KJ, Gordon JA, Sodek J, Hunter GK, Goldberg HA (2003). "Delineation of the hydroxyapatite-nucleating domains of bone sialoprotein." J. Biol. Chem. 278 (10): 7949-55.
Oldberg A, Franzén A, Heinegård D (1988). "The primary structure of a cell-binding bone sialoprotein." J. Biol. Chem. 263 (36): 19430-2.
Tye CE, Hunter GK, Goldberg HA (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.
Vincent K, Durrant MC (2013). "A structural and functional model for human bone sialoprotein." J. Mol. Graph. Model. 39: 108-117.
Wang J, Wang L, Xia B, Yang C, Lai H, Chen X. (2013) “BSP gene silencing inhibits migration, invasion, and bone metastasis of MDA-MB-231BO human breast cancer cells.” PMC. 8(5):e62936.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry