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Beschreibung

Gremlin-1 (UniProt: O60565, also known as Cell proliferation-inducing gene 2 protein, Cysteine knot superfamily 1, BMP antagonist 1, DAN domain family member 2, Down-regulated in Mos-transformed cells protein, Increased in high glucose protein 2, IHG-2) is encoded by the GREM1 (also known as CKTSF1B1, DAND2, DRM, PIG2) gene (Gene ID: 26585 ) in human. Gremlin-1 is a homodimeric cytokine that plays an important role during carcinogenesis and metanephric kidney organogenesis. Two isoforms of Gremlin-1 have been described that are produced by alternative splicing. Gremlin-1 acts as an antagonist of BMP2 and inhibits BMP2-mediated differentiation of osteoblasts. It also down-regulates the BMP4 signaling in a dose-dependent manner. Gremlin-1 is synthesized with a signal peptide (aa 1-24), which is subsequently cleaved off. Gremlin-1 is highly expressed in small intestine where its expression is restricted to intestinal subepithelial myofibroblasts (ISEMFs) at the crypt base. It is also expressed in fetal brain and colon and weak expression is observed in adult brain ovary, prostate, pancreas, and skeletal muscle. Its levels are down-regulated in tumor cell lines. Mutations in GREM1 gene are known to cause Polyposis syndrome, mixed hereditary 1 (HMPS1) that is characterized by apparent autosomal dominant inheritance of multiple types of colorectal polyp, with colorectal carcinoma occurring in a high proportion of affected individuals.