Evidence map›Paper›PMID 32157140›Full record

ArticleScientific reports2020

Identification and functional characterisation of N-linked glycosylation of the orphan G protein-coupled receptor Gpr176.

Tianyu Wang, Shumpei Nakagawa, Takahito Miyake, Genzui Setsu, Sumihiro Kunisue, Kaoru Goto, Akira Hirasawa, Hitoshi Okamura, Yoshiaki Yamaguchi, Masao Doi

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.8field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 36 citations in OpenAlex.

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  11. Oncogenic roles of GPR176 in breast cancer: a potential marker of aggressiveness and a potential target of gene therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
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  15. Exploring the Correlation BetweenPharmacogenomics and personalized medicine · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Tianyu WangDepartment of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto, 606-8501, Japan.
Shumpei NakagawaDepartment of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto, 606-8501, Japan.
Takahito MiyakeDepartment of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto, 606-8501, Japan.
Genzui SetsuDepartment of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto, 606-8501, Japan.
Sumihiro KunisueDepartment of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto, 606-8501, Japan.
Kaoru GotoDepartment of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto, 606-8501, Japan.
Akira HirasawaDepartment of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto, 606-8501, Japan.
Hitoshi OkamuraDepartment of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto, 606-8501, Japan.
Yoshiaki YamaguchiDepartment of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto, 606-8501, Japan.
Masao DoiDepartment of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto, 606-8501, Japan. doimasao@pharm.kyoto-u.ac.jp.
Kyoto University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

G-protein-coupled receptors (GPCRs) are important drug targets with diverse therapeutic applications. However, there are still more than a hundred orphan GPCRs, whose protein functions and biochemical features remain unidentified. Gpr176 encodes a class-A orphan GPCR that has a role in circadian clock regulation in mouse hypothalamus and is also implicated in human breast cancer transcriptional response. Here we show that Gpr176 is N-glycosylated. Peptide-N-glycosidase treatment of mouse hypothalamus extracts revealed that endogenous Gpr176 undergoes N-glycosylation. Using a heterologous expression system, we show that N-glycosylation occurs at four conserved asparagine residues in the N-terminal region of Gpr176. Deficient N-glycosylation due to mutation of these residues reduced the protein expression of Gpr176. At the molecular function level, Gpr176 has constitutive, agonist-independent activity that leads to reduced cAMP synthesis. Although deficient N-glycosylation did not compromise this intrinsic activity, the resultant reduction in protein expression was accompanied by attenuation of cAMP-repressive activity in the cells. We also demonstrate that human GPR176 is N-glycosylated. Importantly, missense variations in the conserved N-glycosylation sites of human GPR176 (rs1473415441; rs761894953) affected N-glycosylation and thereby attenuated protein expression and cAMP-repressive activity in the cells. We show that N-glycosylation is a prerequisite for the efficient protein expression of functional Gpr176/GPR176.

Indexed as

Amino Acid SequenceAnimalsCyclic AMPGlycoside HydrolasesGlycosylationMaleMiceMice, Inbred C57BLMice, KnockoutProtein Processing, Post-TranslationalReceptors, G-Protein-CoupledSequence HomologySignal TransductionCyclic AMPGlycoside HydrolasesGpr176 protein, mouseReceptors, G-Protein-Coupled

Identifiers

PMID32157140
PMCPMC7064540
OpenAlexW3010996038

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.