http://purl.uniprot.org/citations/32636482 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/32636482 | http://www.w3.org/2000/01/rdf-schema#comment | "GPRC6A is proposed to regulate energy metabolism in mice, but in humans a KGKY polymorphism in the third intracellular loop (ICL3) is proposed to result in intracellular retention and loss-of-function. To test physiological importance of this human polymorphism in vivo, we performed targeted genomic humanization of mice by using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated protein 9) system to replace the RKLP sequence in the ICL3 of the GPRC6A mouse gene with the uniquely human KGKY sequence to create Gprc6a-KGKY-knockin mice. Knock-in of a human KGKY sequence resulted in a reduction in basal blood glucose levels and increased circulating serum insulin and FGF-21 concentrations. Gprc6a-KGKY-knockin mice demonstrated improved glucose tolerance, despite impaired insulin sensitivity and enhanced pyruvate-mediated gluconeogenesis. Liver transcriptome analysis of Gprc6a-KGKY-knockin mice identified alterations in glucose, glycogen and fat metabolism pathways. Thus, the uniquely human GPRC6A-KGKY variant appears to be a gain-of-function polymorphism that positively regulates energy metabolism in mice."xsd:string |
http://purl.uniprot.org/citations/32636482 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41598-020-68113-z"xsd:string |
http://purl.uniprot.org/citations/32636482 | http://purl.uniprot.org/core/author | "Lu L."xsd:string |
http://purl.uniprot.org/citations/32636482 | http://purl.uniprot.org/core/author | "Pi M."xsd:string |
http://purl.uniprot.org/citations/32636482 | http://purl.uniprot.org/core/author | "Williams R.W."xsd:string |
http://purl.uniprot.org/citations/32636482 | http://purl.uniprot.org/core/author | "Ye R."xsd:string |
http://purl.uniprot.org/citations/32636482 | http://purl.uniprot.org/core/author | "Xu F."xsd:string |
http://purl.uniprot.org/citations/32636482 | http://purl.uniprot.org/core/author | "Kesterson R.A."xsd:string |
http://purl.uniprot.org/citations/32636482 | http://purl.uniprot.org/core/author | "Quarles L.D."xsd:string |
http://purl.uniprot.org/citations/32636482 | http://purl.uniprot.org/core/author | "Nishimoto S.K."xsd:string |
http://purl.uniprot.org/citations/32636482 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
http://purl.uniprot.org/citations/32636482 | http://purl.uniprot.org/core/name | "Sci Rep"xsd:string |
http://purl.uniprot.org/citations/32636482 | http://purl.uniprot.org/core/pages | "11143"xsd:string |
http://purl.uniprot.org/citations/32636482 | http://purl.uniprot.org/core/title | "Humanized GPRC6AKGKY is a gain-of-function polymorphism in mice."xsd:string |
http://purl.uniprot.org/citations/32636482 | http://purl.uniprot.org/core/volume | "10"xsd:string |
http://purl.uniprot.org/citations/32636482 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32636482 |
http://purl.uniprot.org/citations/32636482 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/32636482 |
http://purl.uniprot.org/uniprot/#_Q5T6X5-mappedCitation-32636482 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32636482 |
http://purl.uniprot.org/uniprot/#_Q8K4Z6-mappedCitation-32636482 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32636482 |
http://purl.uniprot.org/uniprot/Q5T6X5 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/32636482 |
http://purl.uniprot.org/uniprot/Q8K4Z6 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/32636482 |