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GPR158 Membrane Protein Introduction

Introduction of GPR158

GPR158 is encoded by the GPR158 gene which is located at 10p12.31, and the mass of GPR158 is 135,489 Da. It belongs to the G-protein-coupled receptor (GPCR) family which is implicated in many physiological and disease processes, making them important therapeutic drug targets. Newly synthesized GPR158 will traffic to the plasma membrane for the first time, it rapidly undergoes endocytosis and translocation to the nucleus. Generally, GPR158 is expressed at highest levels in the brain, but also in a variety of other cell types.

Basic Information of GPR158
Protein Name Probable G-protein coupled receptor 158
Gene Name GPR158
Aliases KIAA1136
Organism Homo sapiens (Human)
UniProt ID Q5T848
Transmembrane Times 7
Length (aa) 1,215
Sequence GAMAYPLLLCLLLAQLGLGAVGASRDPQGRPDSPRERTPKGKPHAQQPGRASASDSSAPWSRSTDGTILAQKLAEEVPMDVASYLYTGDSHQLKRANCSGRYELAGLPGKWPALASAHPSLHRALDTLTHATNFLNVMLQSNKSREQNLQDDLDWYQALVWSLLEGEPSISRAAITFSTDSLSAPAPQVFLQATREESRILLQDLSSSAPHLANATLETEWFHGLRRKWRPHLHRRGPNQGPRGLGHSWRRKDGLGGDKSHFKWSPPYLECENGSYKPGWLVTLSSAIYGLQPNLVPEFRGVMKVDINLQKVDIDQCSSDGWFSGTHKCHLNNSECMPIKGLGFVLGAYECICKAGFYHPGVLPVNNFRRRGPDQHISGSTKDVSEEAYVCLPCREGCPFCADDSPCFVQEDKYLRLAIISFQALCMLLDFVSMLVVYHFRKAKSIRASGLILLETILFGSLLLYFPVVILYFEPSTFRCILLRWARLLGFATVYGTVTLKLHRVLKVFLSRTAQRIPYMTGGRVMRMLAVILLVVFWFLIGWTSSVCQNLEKQISLIGQGKTSDHLIFNMCLIDRWDYMTAVAEFLFLLWGVYLCYAVRTVPSAFHEPRYMAVAVHNELIISAIFHTIRFVLASRLQSDWMLMLYFAHTHLTVTVTIGLLLIPKFSHSSNNPRDDIATEAYEDELDMGRSGSYLNSSINSAWSEHSLDPEDIRDELKKLYAQLEIYKRKKMITNNPHLQKKRCSKKGLGRSIMRRITEIPETVSRQCSKEDKEGADHGTAKGTALIRKNPPESSGNTGKSKEETLKNRVFSLKKSHSTYDHVRDQTEESSSLPTESQEEETTENSTLESLSGKKLTQKLKEDSEAESTESVPLVCKSASAHNLSSEKKTGHPRTSMLQKSLSVIASAKEKTLGLAGKTQTAGVEERTKSQKPLPKDKETNRNHSNSDNTETKDPAPQNSNPAEEPRKPQKSGIMKQQRVNPTTANSDLNPGTTQMKDNFDIGEVCPWEVYDLTPGPVPSESKVQKHVSIVASEMEKNPTFSLKEKSHHKPKAAEVCQQSNQKRIDKAEVCLWESQGQSILEDEKLLISKTPVLPERAKEENGGQPRAANVCAGQSEELPPKAVASKTENENLNQIGHQEKKTSSSEENVRGSYNSSNNFQQPLTSRAEVCPWEFETPAQPNAGRSVALPASSALSANKIAGPRKEEIWDSFKV

Function of GPR158 Membrane Protein

The activity of GPR158 is mediated by G proteins. On the one hand, GPR158 expression is associated with a neuroendocrine (NE) differentiation phenotype and promotes anchorage-independent colony formation which implies a role for GPR158 in therapeutic progression and tumor formation. On the other hand, GPR158 can promote prostate cancer cell proliferation without androgen receptor (AR) which means GPR158 acting by mechanisms different from other GPCRs. In term of structure, GPR158 has 8 helices at the proximal end of its C-terminal cytoplasmic tail (AA 711-731), a signal peptide (AA 1-23), Ca2+-binding EGF-like domain (AA 314-359) and a leucine zipper domain (AA 108-136) within the N-terminal extracellular domain, and a signature motif characteristic of the metabotropic glutamate receptor family (AA 444-466) at the start of the 7th helix. Beyond that, it has been reported that GPR158 is glucocorticoid-inducible through transcriptional mechanisms in TBM cells derived from the eye’s aqueous outflow pathway.

 The schematic representation of two-dimensional structure of GPR158 Fig.1 The schematic representation of two-dimensional structure of GPR158 (Patel, 2013).

Application of GPR158 Membrane Protein in Literature

  1. Orlandi C., et al. Orphan Receptor GPR158 Is an Allosteric Modulator of RGS7 Catalytic Activity with an Essential Role in Dictating Its Expression and Localization in the Brain. Journal of Biological Chemistry. 2015, 290(22):13622. PubMed ID: 25792749

    The results of this research establish GPR158 as an essential regulator of RGS7 in the native nervous system with a critical role in controlling its expression, membrane localization, and catalytic activity.

  2. Orlandi C., et al. GPR158/179 regulate G protein signaling by controlling localization and activity of the RGS7 complexes. Journal of Cell Biology. 2012, 197(6):711. PubMed ID: 22689652

    This article reveals that GPR158 and GPR179 regulate G protein signaling by controlling localization and activity of the RGS7 complexes, these findings for the first time describe the role of the orphan GPCRs GPR158 in the regulation of G protein signaling.

  3. Patel N., et al. GPR158, an Orphan Member of G Protein-Coupled Receptor Family C: Glucocorticoid-Stimulated Expression and Novel Nuclear Role. Plos One. 2013, 8(2): e57843. PubMed ID: 23451275

    This article performs a study to suggest a functional relationship between glucocorticoid (GC)-induced ocular hypertension and GPR158, one of three orphan members of the GPCR Family C.

  4. Patel N., et al. Expression and Functional Role of Orphan Receptor GPR158 in Prostate Cancer Growth and Progression. Plos One. 2015, 10(2): e0117758. PubMed ID: 25693195

    The findings in this article provide intriguing evidence of a role for the newly characterized glutamate family member GPR158 in PCa growth and progression.

  5. Sutton L. P., et al. Orphan receptor GPR158 controls stress-induced depression. Elife. 2018, 7. PubMed ID: 29419376

    This article identifies a previously unknown role of orphan receptor GPR158 in stress-induced depression leading to better understanding of molecular changes in the disease and providing a promising lead for pharmacological intervention.

GPR158 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-GPR158 antibody development services.


As a forward-looking research institute as well as a leading customer service provider in the field of membrane protein, Creative Biolabs has won good reputation among our worldwide customers for successfully accomplishing numerous challenging projects including generation of many functional membrane proteins. Please feel free to contact us for more information.

Reference

  1. Patel N, et al. (2013). Gpr158, an orphan member of g protein-coupled receptor family c: glucocorticoid-stimulated expression and novel nuclear role. Plos One. 8(2), e57843.

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