SPARC (also known as BM-40 or osteonectin) is a matricellular protein essential for embryo development in invertebrates and highly expressed in bone []. It participates in normal tissue remodeling as it regulates the deposition of extracellular matrix, as well as in neoplastic transformation []. It is involved in extracellular matrix (ECM) assembly and fibrosis through binding both fibrillar collagen and basal lamina collagen IV []. It regulates the activity of matrix metalloproteinases (MMPs), as well as the growth factor signaling mediated by cell surface receptors including vascular endothelial growth factor (VEGF) receptor, basic fibroblast growth factor (bFGF), and transforming growth factor (TGF) beta1. Overexpression of SPARC has been linked to cancers []. SPARC is also a bone-associated protein that has a major role in bone development and mineralisation. It is involved in the initiation and progression of vascular calcification and upregulated by adiponectin []. Furthermore, SPARC may be one of the molecules that govern the uptake and delivery of proteins from blood to the cerebrospinal fluid (CSF) during brain development [].SPARC contains an N-terminal acidic 52-residue segment followed by a follistatin-like (FS) domain, and an α-helical EC domain with 2 unusual calcium-binding EF-hands and the collagen-binding site []. Platelet-derived growth factor (PDGF) interacts with its EC domain, but in a calcium-independent manner, whereas collagen binding is calcium-dependent [, , ].
This group represents a SPARC-like (Secreted Protein Acidic and Rich in Cysteine) protein 1 (SPARCL1; also known as Hevin). SPARCL1 is a secreted glycoprotein, belonging to SPARC family of matricellular proteins []. SPARCL1 is downregulated in various tumours and may have a tumor-suppressor function [, ].
This entry represents the calcium-binding domain found in SPARC (Secreted Protein Acidic and Rich in Cysteine) and Testican (also known as SPOCK; or SParc/Osteonectin, Cwcv and Kazal-like domains) proteins. SPARC proteins are down-regulated in various tumours and may have a tumour-suppressor function [, ]. Testican-3 appears to be a novel regulator that reduces the activity of matrix metalloproteinase (MMP) in adult T-cell leukemia (ATL) [].This cysteine-rich domain is responsible for the anti-spreading activity of human urothelial cells. This extracellular calcium-binding domain is rich in α-helices and contains two EF-hands that each coordinates one Ca2+ ion, forming a helix-loop-helix structure that not only drives the conformation of the protein but is also necessary for biological activity. The anti-spreading activity was dependent on the coordination of Ca2+ by a Glu residue at the Z position of EF-hand 2 [].
