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Molecular SIBLINGs in Health and Disease

The SIBLING gene family

A family of secreted proteins, termed SIBLINGs (for SmallIntegrin-Binding LIgand, N-linked Glycoproteins), contains the integrin-binding tripeptide, Arg-Gly-Asp (RGD), as well as several conserved phosphorylation and N-glycosylation sites [1]. All of the genes cluster on human chromosome 4 and are normally restricted in expression to skeletal tissue. There are currently six known members of the SIBLING family: bone sialoprotein (BSP), osteopontin (OPN), dentin matrix protein (DMP1), dentin sialophosphoprotein (DSPP), matrix extracellular phosphoglycoprotein (MEPE), and enamelin (ENAM) Fig. 1 [2].  

Figure 1. The SIBLING family cluster and structure. (A) Genes encoding bone-specific sialoproteins I and II (OPN and BSP), dentin-specific proteins (DMP1 and DSPP), enamelin-specific protein (ENAM) and a skeletal protein (MEPE) have been localized to the same region of chromosome 4q21 – 25. (B) Characteristics of this family include 1) an integrin-binding tripeptide, RGD; 2) a large percentage of the amino acids are acidic; 3) several casein kinase II type phosphorylation sites (SSEE); 4) proline-rich regions (PPPP); and 5) very similar intron-exon structures (e.g. - type 0 introns with exon 1 being noncoding, while exon 2 contains leader sequence + first two amino acids of the mature protein). Heavily lined boxes indicate known splice variants