Introduction of GPR135
GPR135 is the translation product of gene GPR135. It belongs to the G-protein-coupled receptor (GPCR) family which comprises the largest family of receptors detecting signal molecules, such as neurotransmitters, chemokines, hormones or odorants. GPRs play central roles in the neuronal control of body functions, neuronal differentiation, neuronal growth and the formation of synaptic contacts. GPR135 is a seven-pass membrane protein, consisted of 494 amino acids. The protein sequence is highly homologous between different species, such as human, mice, and rats.
|Basic Information of GPR135|
|Protein Name||G-protein coupled receptor 135|
|Organism||Homo sapiens (Human)|
Function of GPR135 Membrane Protein
GPR135 is widely expressed in brain and some other tissues including pancreatic beta-cells, which can secrete insulin to maintain glucostasis. As a possible regulatory factor in energy metabolism, GPR135 has the capacity to activate intracellular signaling pathways in a spontaneous and melatonin-dependent manner. Belonging to the melatonin receptor subfamily, GPR135 shows extensive spontaneous melatonin-unbound activities on the cAMP, inositol phosphate and ß-arrestin recruitment. Simultaneously, GPR135 performs a reciprocal regulatory interaction with the melatonin receptor MTNR1B most likely through receptor heteromerization. In an epigenetic study, GPR135 was identified as one of the methylated placental genes associated with maternal cigarette smoking during pregnancy, a condition known to increase the risk for miscarriage, low birth weight, preterm birth, and obesity.
Fig.1 The reciprocal interaction between MT2 receptors and GPR61, GPR62 and GPR135. (Oishi A, 2017)
Application of GPR135 Membrane Protein in Literature
This article shows that GPR61, GPR62 and GPR135 are unable to bind melatonin to trigger the signaling pathway. Meanwhile, the three receptors showed widely spontaneous ligand-independent activities on the cAMP, inositol phosphate and ß-arrestin pathways. They also have a reciprocal regulatory interaction with MT2 receptors.
Aided by RNA-Seq, the authors discover GPR18, GPR137 and GPR135 are most highly expressed in human spermatozoa when compared with other GPCRs. Stimulation of GPR18 can induce the phosphorylation of 12 protein kinases to involve in the acrosome reaction.
The article highlights that GPR135 is significantly hypermethylated in lung cancer by statistical analysis and the high methylation is significantly associated with asbestos exposure. So it is consistent that the methylation changes in tumors may be specific for risk factors, such as asbestos exposure.
This article shows that GPR135 is a target for hypermethylation in ovarian cancer genesis after TGF-β stimulation, and the methylation changes will sustaine until the cytokine removal. Pathway analysis showed that the high methylation may impact on the cancer progression, including cellular movement, cell cycle, organ morphology, cellular development, and cell death and survival.
GPR135 Preparation Options
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