Gremlin-1 (GREM1) Active Protein

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, signal peptide; Secreted

Cellular Component: extracellular space; cell surface; extracellular region

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

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