Bone sialoprotein
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Integrin-binding sialoprotein | |||||||||||||
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Identifiers | |||||||||||||
Symbols | IBSP ; BNSP; BSP; BSP-II; SP-II | ||||||||||||
External IDs | OMIM: 147563 MGI: 96389 HomoloGene: 3644 GeneCards: IBSP Gene | ||||||||||||
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Orthologs | |||||||||||||
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: 87.8 – 87.81 Mb |
Chr 5: 104.3 – 104.31 Mb |
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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]
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.[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.
Function
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]
References
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Further reading
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