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: 2 E4|2 57.43 cM
Cellular Component: cell surface; extracellular space
Molecular Function: heparan sulfate proteoglycan binding; protein homodimerization activity; receptor agonist activity; transmembrane receptor protein tyrosine kinase activator activity; vascular endothelial growth factor receptor 2 binding
Biological Process: activation of NF-kappaB transcription factor; angiogenesis; cell migration during sprouting angiogenesis; cell morphogenesis; cell-cell signaling; collagen fibril organization; determination of dorsal identity; embryonic limb morphogenesis; endothelial cell migration; limb development; negative regulation of apoptosis; negative regulation of BMP signaling pathway; negative regulation of bone mineralization; negative regulation of bone remodeling; negative regulation of cell growth; negative regulation of chondrocyte differentiation; negative regulation of leukocyte chemotaxis; negative regulation of osteoblast differentiation; negative regulation of osteoblast proliferation; negative regulation of transcription, DNA-dependent; organ morphogenesis; positive regulation of angiogenesis; positive regulation of cell proliferation; positive regulation of NF-kappaB import into nucleus; positive regulation of receptor internalization; positive regulation of telomerase activity; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; proximal/distal pattern formation; regulation of focal adhesion formation; regulation of stress-activated MAPK cascade; signal transduction; ureteric bud branching
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