InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: GREM1

Summary

InnateDB Protein

IDBP-595574.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

GREM1

Protein Name

gremlin 1

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000453141

InnateDB Gene

IDBG-5193 (GREM1)

Protein Structure

UniProt Annotation

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}.

Subcellular Localization

Secreted {ECO:0000305}.

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}.

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}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 4 experimentally validated interaction(s) in this database.

Experimentally validated
Total	4 [view]
Protein-Protein	4 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005125	cytokine activity
GO:0005515	protein binding
GO:0016015	morphogen activity
GO:0030297	transmembrane receptor protein tyrosine kinase activator activity
GO:0036122	BMP binding
GO:0043184	vascular endothelial growth factor receptor 2 binding
GO:0048018	receptor agonist activity

Biological Process

GO:0000902	cell morphogenesis
GO:0002042	cell migration involved in sprouting angiogenesis
GO:0002092	positive regulation of receptor internalization
GO:0003257	positive regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation
GO:0007165	signal transduction
GO:0007171	activation of transmembrane receptor protein tyrosine kinase activity
GO:0008284	positive regulation of cell proliferation
GO:0010717	regulation of epithelial to mesenchymal transition
GO:0030199	collagen fibril organization
GO:0030502	negative regulation of bone mineralization
GO:0030514	negative regulation of BMP signaling pathway
GO:0033689	negative regulation of osteoblast proliferation
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046851	negative regulation of bone remodeling
GO:0048263	determination of dorsal identity
GO:0051973	positive regulation of telomerase activity
GO:0060394	negative regulation of pathway-restricted SMAD protein phosphorylation
GO:0090027	negative regulation of monocyte chemotaxis
GO:0090090	negative regulation of canonical Wnt signaling pathway
GO:0090291	negative regulation of osteoclast proliferation
GO:1900086	positive regulation of peptidyl-tyrosine autophosphorylation
GO:1900155	negative regulation of bone trabecula formation
GO:1900158	negative regulation of bone mineralization involved in bone maturation
GO:2000273	positive regulation of receptor activity
GO:2000727	positive regulation of cardiac muscle cell differentiation