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Identification of novel splice variants of Adhesion G protein-coupled receptors
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. (Farmakologi 3)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. (Farmakologi 3)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. (Farmakologi 3)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. (Farmakologi 3)
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2007 (English)In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 387, no 1-2, 38-48 p.Article in journal (Refereed) Published
Abstract [en]

Alternative splicing is an important mechanism to generate proteome diversity in higher eukaryotic organisms. We searched for splice variants of the human Adhesion family of G protein-coupled receptors (GPCRs) using mRNA sequences and expressed sequence tags. The results presented here describe 53 human splice variants among the 33 Adhesion GPCRs. Many of these variants appear to be coding for “functional” proteins (29) while the others are seemingly “non-functional” (24). Novel functional splice variants were found for: CD97, CELR3, EMR2, EMR3, GPR56, GPR110, GPR112–GPR114, GPR116, GPR123–GPR126, GPR133, HE6, and LEC1–LEC3. Splice variants for GPR116, GPR125, GPR126, and HE6 were found conserved in other species. Several of the functional splice variants lack one or more of the functional domains that are found in the N-termini of these receptors. These functional domains are likely to affect ligand binding or interaction with other proteins and these novel splice variants may have important roles for the specificity of interactions between these receptors and extracellular molecules. Another type of splice variants found here lacks a GPCR proteolytic site (GPS). The GPS domain has been shown to be essential for the proteolytic cleavage of the receptors N-termini and for cellular surface expression. We suggest that these alternative splice variants may be crucial for the function of the receptors while the seemingly non-functional splice variants may be a part of a regulative mechanism.

Place, publisher, year, edition, pages
2007. Vol. 387, no 1-2, 38-48 p.
Keyword [en]
GPCR; Clan B2, EGF-7TM, Splice variants, N-termini, Functional domains
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-94121DOI: 10.1016/j.gene.2006.07.039ISI: 000243761300006OAI: oai:DiVA.org:uu-94121DiVA: diva2:167867
Available from: 2006-03-22 Created: 2006-03-22 Last updated: 2017-12-14Bibliographically approved
In thesis
1. The Gene Repertoire of G protein-coupled Receptors: New Genes, Phylogeny, and Evolution
Open this publication in new window or tab >>The Gene Repertoire of G protein-coupled Receptors: New Genes, Phylogeny, and Evolution
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The superfamily of G protein-coupled receptors (GPCRs) is one of the largest protein families of mammalian genomes and can be divided into five main families; Glutamate, Rhodopsin, Adhesion, Frizzled, and Secretin. GPCRs participate in most major physiological functions, contributing to the fact that they are important targets in drug discovery. In paper I we mined the human and mouse genomes for new Adhesion GPCR genes. We found two new human genes (GPR133 and GPR144) and 17 mouse Adhesion genes, bringing the number up to 33 human and 31 mouse genes. In paper II we describe 53 new splice variants for human Adhesion receptors supported by expressed sequence tags (EST) data. 29 of these variants seem to code for functional proteins, several of which lack one or more functional domains in the N-termini. Lack of certain domains is likely to affect ligand binding or interaction with other proteins. Paper III describes the Glutamate GPCR in human, mouse, Fugu, and zebrafish. We gathered a total of 22 human, 79 mouse, 30 Fugu, and 32 zebrafish sequences and grouped these into eight clans using phylogenetic methods. The report provides an overview of the expansion or deletions among the different branches of the Glutamate receptor family. Paper IV focuses on the trace amine (TA) clan of Rhodopsin GPCRs. We identified 18 new rodent genes, 57 zebrafish genes, and eight Fugu genes belonging to the clan. Chromosomal mapping together with phylogenetic relationships suggests that the family arose through several mechanisms involving tetraploidisation, block duplications, and local duplication events. Paper V provides a comprehensive dataset of the GPCR superfamily of human and mouse containing 495 mouse and 400 human non-olfactory GPCRs. Phylogenetic analyses showed that 329 of the receptors are found in one-to-one orthologous pairs, whereas other receptors may have originated from species-specific expansions.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 65 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 121
Keyword
Pharmacology, Bioinformatics, Evolution, GPCR, Phylogeny, Farmakologi
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-6627 (URN)91-554-6489-0 (ISBN)
Public defence
2006-04-12, Room B21, BMC, Husargatan 3, Uppsala, 09:15
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Supervisors
Available from: 2006-03-22 Created: 2006-03-22 Last updated: 2018-01-13Bibliographically approved

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