Introduction of ADGRF5
ADGRF5, also known as G-protein coupled receptor 116 (GPR116), is a protein encoded by the human GPR116 gene. It is a member of the adhesion class of GPCRs (AdGPCRs), which share extracellular domains containing highly conserved GPCR autoproteolysis-inducing (GAIN) domains. During synthesis of ADGRF5, intracellular autoproteolytic processing of nascent ADGRF5 proteins within the GAIN domain generates a mature protein, consisting of an N-terminal fragment (NTF) that is noncovalently linked to the C-terminal fragment (CTF), consisting of a 7 transmembrane (7TM) domain and a cytoplasmic domain.
|Basic Information of ADGRF5|
|Protein Name||Adhesion G-protein coupled receptor F5|
|Aliases||G-protein coupled receptor 116|
|Organism||Homo sapiens (Human)|
Function of ADGRF5 Membrane Protein
ADGRF5 is a member of the adhesion sub-type of GPCRs family, which is composed of 33 members in humans with a variety of distribution in embryonic cells, reproductive tract cells, leukocytes, neurons, and tumor cells. Studies have suggested that the expression of ADGRF5 is mainly restricted in the alveolar wall of the human lung. AND the expression of ADGRF5 is also found in early mouse embryos. It has been reported that ADGRF5 plays a key role in lung surfactant homeostasis, and lack of GPR116 could lead to progressive accumulation of surfactant lipids and proteins in the alveolar space of mice. More recently, loss of Gpr116 has also been reported to result in a subtle vascular phenotype including a leakiness of the blood-brain-barrier and a reduced pathological response in a model of oxygen-induced retinopathy. What’s more, GPR116 may also be strongly correlated with breast cancer stage, metastasis, and progression through the Gaq-p63RhoGEF-Rho GTPase signaling pathway.
Fig.1 Model of GPR116 protein structure.
Application of ADGRF5 Membrane Protein in Literature
1. Lu S., et.al. Developmental vascular remodeling defects and postnatal kidney failure in mice lacking Gpr116 (Adgrf5) and Eltd1 (Adgrl4). PloS one. 2017, e0183166. PubMed ID: 28806758
This article proves that the loss of GPR116 and ELTD1 specifically in endothelial cells or neural crest-derived cells don’t recapitulate any of the phenotypes observed in GPR116-ELTD1 double-deficient mice, which indicates that loss of GPR116 and ELTD1 expressed by other cells accounts for the observed cardiovascular and renal defects.
2. Yang L., et.al. High expression of GPR116 indicates poor survival outcome and promotes tumor progression in colorectal carcinoma. Oncotarget. 2017, 8(29): 47943. PubMed ID: 28624786
This article suggests that the ability of proliferation and invasion of CRC cell lines HCT116 and LOVO was markedly reduced after transfected with siRNA-GPR116. What’s more, GPR116 may drive EMT in CRC cells through AKT/EKR signaling pathway, resulting in metastasis. It indicates that GPR116 may be a novel reliable prognostic indicator and a risk factor in CRC progression.
3. Brown K., et.al. Epithelial Gpr116 regulates pulmonary alveolar homeostasis via Gq/11 signaling. JCI insight. 2017, 2(11). PubMed ID: 28570277
This article shows that human and mouse GPR116 control surfactant secretion and reuptake in alveolar type II (AT2) cells by regulating guanine nucleotide-binding domain α q and 11 (Gq/11) signaling. It indicates that GPR116 is a plausible therapeutic target to modulate endogenous alveolar surfactant pools to treat pulmonary diseases associated with surfactant dysfunction.
4. Niaudet C., et.al. Gpr116 receptor regulates distinctive functions in pneumocytes and vascular endothelium. PloS one. 2015, 10(9): e0137949. PubMed ID: 26394398
This article shows that endothelial-specific deletion of Gpr116 results in a significant increase of the brain vascular leakage, which indicates that Gpr116 has a new role in the central nervous system vasculature for it has the ability to modulate endothelial properties.
5. Tang X., et.al. GPR116, an Adhesion G-Protein-Coupled Receptor, Promotes Breast Cancer Metastasis via the Gαq-p63RhoGEF-Rho GTPase Pathway. Cancer research. 2013, 73(20): 6206-18. PubMed ID: 24008316
This article suggests that GPR116 is crucial for the metastasis of breast cancer and support GPR116 as a potential prognostic marker and drug target against metastatic human breast cancer.
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