InnateDB Protein
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IDBP-595574.3
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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GREM1
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Protein Name
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gremlin 1
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Synonyms
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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000453141
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InnateDB Gene
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IDBG-5193 (GREM1)
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Protein Structure
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Function |
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 (By similarity). {ECO:0000250}.
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Subcellular Localization |
Secreted {ECO:0000305}.
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Disease Associations |
Polyposis syndrome, mixed hereditary 1 (HMPS1) [MIM:601228]: 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. {ECO:0000269PubMed:22561515}. Note=The disease is caused by mutations affecting the gene represented in this entry. HMPS1 is caused by a duplication spanning the 3' end of the SCG5 gene and a region upstream of the GREM1 locus. This duplication is associated with increased allele-specific GREM1 expression that may cause reduced bone morphogenetic protein (BMP) pathway activity. This mechanism also underlies tumorigenesis in juvenile polyposis of the large bowel (PubMed:22561515). {ECO:0000269PubMed:22561515}.
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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. {ECO:0000269PubMed:10894942, ECO:0000269PubMed:22561515}.
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 4 experimentally validated interaction(s) in this database.
Experimentally validated |
Total |
4
[view]
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Protein-Protein |
4
[view]
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Protein-DNA |
0
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Molecular Function |
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Biological Process |
GO:0000902
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cell morphogenesis
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GO:0002042
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cell migration involved in sprouting angiogenesis
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GO:0002092
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positive regulation of receptor internalization
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GO:0003257
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positive regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation
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GO:0007165
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signal transduction
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GO:0007171
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activation of transmembrane receptor protein tyrosine kinase activity
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GO:0008284
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positive regulation of cell proliferation
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GO:0010717
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regulation of epithelial to mesenchymal transition
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GO:0030199
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collagen fibril organization
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GO:0030502
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negative regulation of bone mineralization
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GO:0030514
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negative regulation of BMP signaling pathway
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GO:0033689
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negative regulation of osteoblast proliferation
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GO:0045944
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positive regulation of transcription from RNA polymerase II promoter
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GO:0046851
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negative regulation of bone remodeling
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GO:0048263
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determination of dorsal identity
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GO:0051973
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positive regulation of telomerase activity
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GO:0060394
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negative regulation of pathway-restricted SMAD protein phosphorylation
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GO:0090027
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negative regulation of monocyte chemotaxis
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GO:0090090
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negative regulation of canonical Wnt signaling pathway
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GO:0090291
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negative regulation of osteoclast proliferation
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GO:1900086
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positive regulation of peptidyl-tyrosine autophosphorylation
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GO:1900155
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negative regulation of bone trabecula formation
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GO:1900158
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negative regulation of bone mineralization involved in bone maturation
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GO:2000273
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positive regulation of receptor activity
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GO:2000727
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positive regulation of cardiac muscle cell differentiation
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Cellular Component |
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PDB ID |
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InterPro |
IPR004133
DAN
IPR006207
Cystine knot, C-terminal
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PFAM |
PF03045
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PRINTS |
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PIRSF |
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SMART |
SM00041
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TIGRFAMs |
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Modification |
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SwissProt |
O60565
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PhosphoSite |
PhosphoSite-O60565
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TrEMBL |
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UniProt Splice Variant |
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Entrez Gene |
26585
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UniGene |
Hs.607314
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RefSeq |
NP_001178252
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HUGO |
HGNC:2001
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OMIM |
603054
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CCDS |
CCDS53927
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HPRD |
07048
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IMGT |
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EMBL |
AB032372
AF045800
AF110137
AF154054
AK095890
AY232290
BC069525
BC093778
BC101611
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GenPept |
AAC39725
AAF06677
AAG23891
AAH69525
AAH93778
AAI01612
AAP69985
BAA84462
BAC04643
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