Gremlin-1 Recombinant Protein | GREM1 recombinant protein

Human Gremlin-1

Cat. Num. AAA691636

• Gene Names: GREM1; DRM; HMPS; PIG2; CRAC1; DAND2; IHG-2; GREMLIN; CKTSF1B1
• Reactivity: Human
• Purity: > 95% by SDS-PAGE & silver stain
• Synonyms: Gremlin-1; Human Gremlin-1; Recombinant Human Gremlin-1; Cell proliferation-inducing gene 2 protein; BMP antagonist 1; GREM1 recombinant protein

• Host: E Coli
• Reactivity: Human
• Purity/Purification: > 95% by SDS-PAGE & silver stain
• Form/Format: Lyophilized
• Sequence: MKKKGSQGAIPPPDKAQHNDSEQTQSPQQPGSRNRGRGQGRGTAMPGEEV LESSQEALHVTERKYLKRDWCKTQPLKQTIHEEGCNSRTIINRFCYGQCN SFYIPRHIRKEEGSFQSCSFCKPKKFTTMMVTLNCPELQPPTKKKRVTRV KQCRCISIDLD
• Sequence Length: 161

• N Terminal Sequence: MKKKGSQGAI
• Buffer: 50 mM acetic acid
• Reconstitution: Human Grem-1 should be reconstituted in 50 mM acetid acid or water to a concentration of 0.1 mg/mL. This solution can be diluted in water or other buffer solutions or stored at -20°C.
• Preparation and Storage: The lyophilized human Grem1, though stable at room temperature, is best stored desiccated below 0 degree C. Avoid repeated freeze-thaw cycles.

Testing Data

Related Product Information for GREM1 recombinant protein

Gremlin, also known as "Increased in High Glucose protein 2" (IHG2) and "Down regulated in Mos-transformed cells protein" (Drm), is a 28 kDa member of the Dan family of secreted glycoproteins. Native human Gremlin consist of 160 amino acids. The mature region contains one potential site for N-linked glycosylation (Asn42), a cysteine-rich region, and a cysteine-knot motif (aa94-184) whose structure is shared by members of the TGFbeta superfamily. Posttranslational modifications include glycosylation and phosphorylation (1-3). Human Gremlin exists in both secreted and membrane-associated forms and there exist 2 isoforms. The aa sequence identity of human Gremlin with mouse and chicken Gremlin is 99% and 86%, respectively. Northern blot analysis shows that Gremlin mRNA is highly expressed in the small intestine, fetal brain and colon, and weakly expressed in adult brain, ovary, prostate, pancreas and skeletal muscle. Gremlin functions as a bone morphogenetic protein (BMP) antagonist. It acts by binding to, and forming heterodimers with, BMP2, BMP4, and BMP7, thus preventing them from interacting with their cell surface receptors. This mechanism is thought to be responsible for the pattern-inducing activity of Gremlin during embryonic development and to play a role in human diseases, such as diabetic nephropathy). However, intracellular BMP-independent mechanisms of action may mediate the ability of Gremlin to suppress transformation and tumor genesis under certain experimental conditions. Gremlin also interacts with Slit proteins and acts as an inhibitor of monocyte chemotaxis. In addition, Gremlin has been found to be a proangiogenic factor expressed by endothelium. Furthermore Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2.

Product Categories/Family for GREM1 recombinant protein

Cytokines & Growth Factors

References

Mitola S et al, Blood (2010); Wordinger RJ et al, Exp Eye Res (2008); Stabile H et al, Blood (2007); Chen B et al, J Immunol (2004); Khokha MK et al, Nat. Genet (2003)

NCBI and Uniprot Product Information

• NCBI GI #: 300797328
• NCBI GeneID: 26585
• NCBI Accession #: NP_037504.1
• NCBI GenBank Nucleotide #: NM_013372.6
• UniProt Accession #: O60565; Q52LV3; Q8N914; Q8N936
• Molecular Weight: 18.4 kDa
• NCBI Official Full Name: gremlin-1 isoform 2
• NCBI Official Synonym Full Names: gremlin 1, DAN family BMP antagonist
• NCBI Official Symbol: GREM1
• NCBI Official Synonym Symbols: DRM; HMPS; PIG2; CRAC1; DAND2; IHG-2; GREMLIN; CKTSF1B1
• NCBI Protein Information: gremlin-1; gremlin 1-like protein; DAN domain family member 2; increased in high glucose-2; colorectal adenoma and carcinoma 1; cell proliferation-inducing gene 2 protein; cysteine knot superfamily 1, BMP antagonist 1; gremlin 1, cysteine knot superfamily, homolog; down-regulated in Mos-transformed cells protein
• UniProt Protein Name: Gremlin-1
• Protein Family: Gremlin
• UniProt Gene Name: GREM1
• UniProt Synonym Gene Names: CKTSF1B1; DAND2; DRM; IHG-2
• UniProt Entry Name: GREM1_HUMAN

NCBI Description

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]

Uniprot Description

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. Ref.3

Subunit structure: Interacts with SLIT1 and SLIT2 in a glycosylation-dependent manner

By similarity.

Subcellular location: Secreted

Probable.

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. Ref.3 Ref.9

Induction: By high glucose through TGFB1-mediated pathways in mesangial cell. Down-regulated in tumor cell lines. Ref.2 Ref.3

Involvement in disease: 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.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 (Ref.9). Ref.9

Sequence similarities: Belongs to the DAN family.Contains 1 CTCK (C-terminal cystine knot-like) domain.