Alternative titles; symbols
HGNC Approved Gene Symbol: SPP2
Cytogenetic location: 2q37.1 Genomic coordinates (GRCh38) : 2:234,050,702-234,077,134 (from NCBI)
Hu et al. (1995) cloned bovine Spp2, which they called Spp24. Spp24 encodes a 24-kD secreted phosphoprotein that shares sequence homology with members of the cystatin family of thiol protease inhibitors and is expressed in bone, as is cystatin. Thiol proteases are known to be involved in bone turnover, and Spp24 may function as an inhibitor.
By searching databases for sequences similar to bovine Spp2, followed by screening a liver cDNA library, Bennett et al. (2004) cloned human SPP2. The deduced 211-amino acid protein contains a 29-amino acid signal peptide, followed by a cystatin-like domain, a region of phosphorylated serines, and an arginine-rich C-terminal domain. mRNA dot blot analysis detected highest SPP2 expression in adult and fetal liver, with much weaker expression in adult kidney. The array used for the expression study did not contain bone mRNA. Bennett et al. (2004) identified protein sequences similar to SPP2 in several mammalian species and in chicken, salmon, and trout.
The fetuin-mineral complex is a high molecular mass complex of calcium, phosphate, fetuin (AHSG; 138680), and MGP (154870) that inhibits calcification of arteries and other soft tissues. Price et al. (2003) determined that Spp24 is also a component of the rat fetuin-mineral complex, suggesting that Spp24 may have a role in inhibiting calcification.
Bennett et al. (2004) determined that the SPP2 gene contains 8 exons and spans about 27 kb. Exon 1 contains the ATG start codon, and exon 7 contains the TAA stop codon. The promoter region has binding sites for NFAT (see 600490), CLOX (CUTL1; 116896), and CEBP (see 116897), but it has no CAAT or TATA boxes.
Using fluorescence in situ hybridization, Swallow et al. (1997) mapped the SPP2 gene to chromosome 2q37-qter. By genomic sequence analysis, Bennett et al. (2004) mapped the SPP2 gene to chromosome 2q37.1.
Bennett, C. S., Khorram Khorshid, H. R., Kitchen, J. A., Arteta, D., Dalgleish, R. Characterization of the human secreted phosphoprotein 24 gene (SPP2) and comparison of the protein sequence in nine species. Matrix Biol. 22: 641-651, 2004. [PubMed: 15062857] [Full Text: https://doi.org/10.1016/j.matbio.2003.12.001]
Hu, B., Coulson, L., Moyer, B., Price, P. A. Isolation and molecular cloning of a novel bone phosphoprotein related in sequence to the cystatin family of thiol protease inhibitors. J. Biol. Chem. 270: 431-436, 1995. Note: Erratum: J. Biol. Chem. 270: 10359 only, 1995. [PubMed: 7814406] [Full Text: https://doi.org/10.1074/jbc.270.1.431]
Price, P. A., Nguyen, T. M. T., Williamson, M. K. Biochemical characterization of the serum fetuin-mineral complex. J. Biol. Chem. 278: 22153-22160, 2003. [PubMed: 12676928] [Full Text: https://doi.org/10.1074/jbc.M300739200]
Swallow, J. E., Merrison, W. K., Gill, P. K., Harris, S., Dalgleish, R. Assignment of secreted phosphoprotein 24 (SPP2) to human chromosome band 2q37-qter by in situ hybridization. Cytogenet. Cell Genet. 79: 142 only, 1997. [PubMed: 9533032] [Full Text: https://doi.org/10.1159/000134702]