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G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. They are coupled with G proteins. They pass through the cell membrane seven times in the form of six loops of amino acid residues, which is why they are sometimes referred to as seven-transmembrane receptors. Ligands can bind either to the extracellular N-terminus and loops or to the binding site within transmembrane helices. They are all activated by agonists, although a spontaneous auto-activation of an empty receptor has also been observed.
Brain-specific angiogenesis inhibitor 3 is a protein that in humans is encoded by the BAI3 gene.
G protein-coupled receptor 64 also known as HE6 is a protein encoded by the ADGRG2 gene. GPR64 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.
Latrophilin 1 is a protein that in humans is encoded by the ADGRL1 gene. It is a member of the adhesion-GPCR family of receptors. Family members are characterized by an extended extracellular region with a variable number of protein domains coupled to a TM7 domain via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.
Latrophilin 3 is a protein that in humans is encoded by the ADGRL3 gene.
Probable G-protein coupled receptor 123 is a protein that in humans is encoded by the GPR123 gene. It is a member of the adhesion-GPCR family of receptors. Family members are normally characterized by an extended extracellular region with a variable number of protein domains coupled to a TM7 domain via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.
G protein-coupled receptor 128 is a protein encoded by the ADGRG7 gene. GPR128 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.
G protein-coupled receptor 112 is a protein encoded by the ADGRG4 gene. GPR112 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.
Adhesion G-protein coupled receptor A3 (ADGRA3), also known as GPR125, is an adhesion GPCR that in humans is encoded by the Adgra3 gene.
G protein-coupled receptor 114 is a protein encoded by the ADGRG5 gene. GPR114 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.
Probable G-protein coupled receptor 116 is a protein that in humans is encoded by the GPR116 gene. GPR116 has now been shown to play an essential role in the regulation of lung surfactant homeostasis.
Probable G-protein coupled receptor 111 is a protein that in humans is encoded by the GPR111 gene.
Probable G-protein coupled receptor 110 is a protein that in humans is encoded by the GPR110 gene. This gene encodes a member of the adhesion-GPCR receptor family. Family members are characterized by an extended extracellular region with a variable number of N-terminal protein modules coupled to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.
Probable G-protein coupled receptor 133 is a protein that in humans is encoded by the GPR133 gene.
Relaxin/insulin-like family peptide receptor 4, also known as RXFP4, is a human G-protein coupled receptor.
Probable G-protein coupled receptor 144 is a protein that in humans is encoded by the GPR144 gene. This gene encodes a member of the adhesion-GPCR family of receptors. Family members are characterised by an extended extracellular region with a variable number of protein domains coupled to a TM7 domain via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.
G protein-coupled receptor 148, also known as GPR148, is a human orphan receptor from GPCR superfamily. It is expressed primarily in nervous system and testis. Is may be implicated in prostate cancer.
Secretin receptor family consists of secretin receptors regulated by peptide hormones from the glucagon hormone family. The family is different from adhesion G protein-coupled receptors.
Latrophilin 2 is a protein that in humans is encoded by the ADGRL2 gene.
Adhesion G protein-coupled receptors are a class of 33 human protein receptors with a broad distribution in embryonic and larval cells, cells of the reproductive tract, neurons, leukocytes, and a variety of tumours. Adhesion GPCRs are found throughout metazoans and are also found in single-celled colony forming choanoflagellates such as Monosiga brevicollis and unicellular organisms such as Filasterea. The defining feature of adhesion GPCRs that distinguishes them from other GPCRs is their hybrid molecular structure. The extracellular region of adhesion GPCRs can be exceptionally long and contain a variety of structural domains that are known for the ability to facilitate cell and matrix interactions. Their extracellular region contains the membrane proximal GAIN domain. Crystallographic and experimental data has shown this structurally conserved domain to mediate autocatalytic processing at a GPCR-proteolytic site (GPS) proximal to the first transmembrane helix. Autocatalytic processing gives rise to an extracellular (α) and a membrane-spanning (β) subunit, which are associated non-covalently, resulting in expression of a heterodimeric receptor at the cell surface. Ligand profiles and in vitro studies have indicated a role for adhesion GPCRs in cell adhesion and migration. Work utilizing genetic models confined this concept by demonstrating that the primary function of adhesion GPCRs may relate to the proper positioning of cells in a variety of organ systems. Moreover, growing evidence implies a role of adhesion GPCRs in tumour cell metastasis. Formal G protein-coupled signalling has been demonstrated for a number for adhesion GPCRs, however, the orphan receptor status of many of the receptors still hampers full characterisation of potential signal transduction pathways. In 2011, the adhesion GPCR consortium was established to facilitate research of the physiological and pathological functions of adhesion GPCRs.
References
- ↑ Lander, ES; Linton, LM; Birren; International Human Genome Sequencing, Consortium; et al. (Feb 15, 2001). "Initial sequencing and analysis of the human genome" (PDF). Nature. 409 (6822): 860–921. Bibcode:2001Natur.409..860L. doi: 10.1038/35057062 . PMID 11237011.
- ↑ Fredriksson, R; Lagerström, MC; Lundin, LG; Schiöth, HB (June 2003). "The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints". Molecular Pharmacology. 63 (6): 1256–72. doi:10.1124/mol.63.6.1256. PMID 12761335.
- ↑ Krishnan, A; Almén, MS; Fredriksson, R; Schiöth, HB (2012). "The origin of GPCRs: identification of mammalian like Rhodopsin, Adhesion, Glutamate and Frizzled GPCRs in fungi". PLOS ONE. 7 (1): e29817. Bibcode:2012PLoSO...729817K. doi: 10.1371/journal.pone.0029817 . PMC 3251606 . PMID 22238661.
- ↑ Nordström KJ, Sällman Almén M, Edstam MM, Fredriksson R, Schiöth HB (September 2011). "Independent HHsearch, Needleman—Wunsch-based, and motif analyses reveal the overall hierarchy for most of the G protein-coupled receptor families". Molecular Biology and Evolution. 28 (9): 2471–80. doi: 10.1093/molbev/msr061 . PMID 21402729.
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