SMOC-1: Proteins and Enzymes

SMOC-1 (secreted, or SPARC-related, modular calcium-binding protein 1) is a 70-90 kDa secreted glycoprotein that is a member of the SPARC family of matricellular molecules. Mature mouse SMOC-1 is 427 amino acids (aa) in length. It contains one Kazal-like domain (aa 42-86), two thyroglobulin type-1 segments (aa 91-157 and 223-291) and two functional EF-hand sequences (aa 358-393 and 395-430). Two splice variants contain an insertion of eleven aa after Lys174, with one of these also including an alternate start site at Met65. Mature mouse SMOC-1 shares 99% aa identity with rat SMOC-1 and 92% aa identity with human, canine and bovine SMOC-1. The principal difference between rodents and other mammals is an additional 19 aa near the C-terminus of rodent SMOC-1. Like other matricellular proteins, SMOC-1 is primarily expressed in basement membranes, although it has also been found in other extracellular matrices and the oocyte zona pellucida. It is present early in mouse embryogenesis, and is produced by cells deriving from all three germ layers. Recombinant bacterially produced human SMOC-1 and SMOC-2 were both shown to bind the acute phase protein, C-reactive protein, and the adhesion proteins, fibulin and vitronectin. A signaling role for SMOC-1 was shown in rat mesangial cells: induction of nitric oxide in response to inflammatory cytokines downregulates SMOC-1 which, in turn, downregulates expression of TGF-beta and TGF-beta-regulated genes. This mechanism is proposed to limit the profibrotic effects of TGF-beta, for example in the glomerulus. In Xenopus, the SMOC paralog has been shown to antagonize BMP activity.