GREM1 Lysate – Tissue Lysate

This gene encodes a member of the BMP (bone morphogenic protein) antagonist family. Like BMPs, BMP antagonists contain cystine knots and typically form homo- and heterodimers. The CAN (cerberus and dan) subfamily of BMP antagonists, to which this gene belongs, is characterized by a C-terminal cystine knot with an eight-membered ring. The antagonistic effect of the secreted glycosylated protein encoded by this gene is likely due to its direct binding to BMP proteins. As an antagonist of BMP, this gene may play a role in regulating organogenesis, body patterning, and tissue differentiation. In mouse, this protein has been shown to relay the sonic hedgehog (SHH) signal from the polarizing region to the apical ectodermal ridge during limb bud outgrowth. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

GREM1: Cytokine that may play an important role during carcinogenesis and metanephric kidney organogenesis, as a BMP antagonist required for early limb outgrowth and patterning in maintaining the FGF4-SHH feedback loop. Down-regulates the BMP4 signaling in a dose-dependent manner. Acts as inhibitor of monocyte chemotaxis. Interacts with SLIT1 and SLIT2 in a glycosylation- dependent manner. By high glucose through TGFB1-mediated pathways in mesangial cell. Down-regulated in tumor cell lines. Highly expressed in small intestine, fetal brain and colon. Weakly expressed in brain, ovary, prostate, pancreas and skeletal muscle. In brain found in the region localized around the internal capsule in the large subcortical nuclei, including caudate, putamen, substantia nigra, thalamus and subthalamus. Predominantly expressed in normal cells including neurons, astrocytes and fibroblasts. Belongs to the DAN family. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: Secreted; Secreted, signal peptide

Chromosomal Location of Human Ortholog: 15q13.3

Cellular Component: extracellular space; cell surface

Molecular Function: morphogen activity; protein binding; transmembrane receptor protein tyrosine kinase activator activity; vascular endothelial growth factor receptor 2 binding; cytokine activity; receptor agonist activity

Biological Process: limb development; transmembrane receptor protein tyrosine kinase activation (dimerization); collagen fibril organization; apoptosis; negative regulation of chondrocyte differentiation; positive regulation of receptor internalization; cell morphogenesis; positive regulation of NF-kappaB import into nucleus; signal transduction; activation of NF-kappaB transcription factor; negative regulation of BMP signaling pathway; negative regulation of bone mineralization; cell-cell signaling; positive regulation of cell proliferation; proximal/distal pattern formation; embryonic limb morphogenesis; determination of dorsal identity; positive regulation of telomerase activity; regulation of stress-activated MAPK cascade; positive regulation of angiogenesis; cell migration during sprouting angiogenesis; ureteric bud branching; negative regulation of bone remodeling; regulation of focal adhesion formation; positive regulation of transcription from RNA polymerase II promoter; negative regulation of osteoblast proliferation; negative regulation of cell growth; negative regulation of transcription, DNA-dependent; negative regulation of apoptosis