From UniProt: Polyposis syndrome, mixed hereditary 1 (HMPS1): A disease characterized by apparent autosomal dominant inheritance of multiple types of colorectal polyp, with colorectal carcinoma occurring in a high proportion of affected individuals. Patients can develop polyps of multiple and mixed morphologies, including serrated lesions, Peutz-Jeghers polyps, juvenile polyps, conventional adenomas and colorectal carcinoma in the absence of any identifiable extra-colonic features. [MIM:601228]

     From NCBI Gene: 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] From UniProt: 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.

The following transcription factors affect gene expression:

• GR
• GR-alpha
• GR-beta
• RORalpha1
• RORalpha2
• STAT3
• AP-2gamma

Tissue specificity:

Highly expressed in small intestine, fetal brain and colon. Expression is restricted to intestinal subepithelial myofibroblasts (ISEMFs) at the crypt base. In subjects with HMPS1, by contrast, GREM1 is expressed, not only in basal ISEMFs, but also at very high levels in epithelial cells (predominantly colonocytes), with expression extending most of the way up the sides of the crypt. 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.

Induction:

By high glucose through TGFB1-mediated pathways in mesangial cell. Down-regulated in tumor cell lines.

Molecular Function:

• Morphogen Activity
• Transmembrane Receptor Protein Tyrosine Kinase Activator Activity
• Bmp Binding
• Vascular Endothelial Growth Factor Receptor 2 Binding
• Receptor Agonist Activity

Biological Processes:

• Cell Morphogenesis
• Branching Involved In Ureteric Bud Morphogenesis
• Cell Migration Involved In Sprouting Angiogenesis
• Positive Regulation Of Receptor Internalization
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter Involved In Myocardial Precursor Cell Differentiation
• Mesenchymal To Epithelial Transition Involved In Metanephros Morphogenesis
• Apoptotic Process
• Signal Transduction
• Cell-Cell Signaling
• Positive Regulation Of Cell Proliferation
• Proximal/Distal Pattern Formation
• Regulation Of Epithelial To Mesenchymal Transition
• Collagen Fibril Organization
• Negative Regulation Of Cell Growth
• Embryonic Limb Morphogenesis
• Negative Regulation Of Bone Mineralization
• Negative Regulation Of Bmp Signaling Pathway
• Negative Regulation Of Chondrocyte Differentiation
• Negative Regulation Of Osteoblast Proliferation
• Positive Regulation Of Nf-Kappab Import Into Nucleus
• Negative Regulation Of Apoptotic Process
• Positive Regulation Of Angiogenesis
• Negative Regulation Of Transcription, Dna-Templated
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
• Negative Regulation Of Bone Remodeling
• Determination Of Dorsal Identity
• Positive Regulation Of Nf-Kappab Transcription Factor Activity
• Regulation Of Focal Adhesion Assembly
• Positive Regulation Of Telomerase Activity
• Limb Development
• Negative Regulation Of Pathway-Restricted Smad Protein Phosphorylation
• Ureteric Bud Formation
• Negative Regulation Of Monocyte Chemotaxis
• Negative Regulation Of Canonical Wnt Signaling Pathway
• Positive Regulation Of Branching Involved In Ureteric Bud Morphogenesis
• Negative Regulation Of Branching Involved In Ureteric Bud Morphogenesis
• Negative Regulation Of Osteoclast Proliferation
• Positive Regulation Of Peptidyl-Tyrosine Autophosphorylation
• Negative Regulation Of Bone Trabecula Formation
• Negative Regulation Of Bone Mineralization Involved In Bone Maturation
• Positive Regulation Of Receptor Activity
• Positive Regulation Of Cardiac Muscle Cell Differentiation