GRAFS

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The GPCR superfamily is the largest gene family in the human genome containing approximately 800 genes. [1] As the vertebrate superfamily can be phylogenetically grouped into five main families the GRAFS classification system has been proposed.

GRAFS stands for Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, Secretin. [2] They correspond to classical classes C (class C, glutamate), A (rhodopsin-like), B2 (Secretin receptor family, long N-terminal), F (Frizzled/Smoothened), and B1+3 (other secretin). [3] Taste2 has more recently considered to be closer to Rhodopsin-like receptors. [4]

See also

Related Research Articles

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Latrophilin 3 is a protein that in humans is encoded by the ADGRL3 gene.

<span class="mw-page-title-main">GPR123</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">GPR112</span> Protein-coding gene in humans

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<span class="mw-page-title-main">GPR125</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">GPR148</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Latrophilin 2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Adhesion G protein-coupled receptor</span> Class of 33 human protein receptors

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

  1. 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.
  2. 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.
  3. 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.
  4. 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.