EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding protein 1 (SMOC-1)
SMOC-1, also termed SPARC-related modular calcium-binding protein 1, or smooth muscle-associated protein 1 (SMAP-1), is an Arf6 GTPase-activating protein (GAP) that directly interacts with clathrin and regulates the clathrin-dependent endocytosis of transferrin receptors from the plasma membrane. It is predominantly localized in basement membranes. SMOC-1 acts as a regulator of osteoblast differentiation and is involved in inhibition of transforming growth factor-beta (TGF-beta) signaling through production of nitric oxide. It also plays an essential role in ocular and limb development and functions as a regulator of bone morphogenic protein (BMP) signaling. It interacts with a matricellular protein, tenascin C in addition to the serum proteins, fibulin-1 and C-reactive protein, but not collagens. Two point mutations in the SMOC1 gene may cause Waardenburg Anophtalmia Syndrome. Moreover, SMOC-1 is involved in direct or indirect modulation of growth factor signaling pathways and plays a role in physiological processes involving extensive tissue remodeling. SMOC-1 contains a follistatin-like (FS) domain, two thyroglobulin-like (TY) domains, a novel domain, which is found only in the homologous SMOC-2, and an extracellular calcium-binding (EC) domain with two EF-hand calcium-binding motifs.