AGRL2-4 , GAIN subdomain A
IPR032471
Definition
This entry describes the GAIN subdomain A primarily found in adhesion G protein-coupled receptors L2-4 (AGRL2-4). It is also found in Latrophilin/CIRL, CELR1, AGRB1-3 and related G-protein-coupled receptors (GPCR). The GAIN domain consist of a stalk (consisting of subdomains A and B) and a GPS motif [interpro:IPR000203], followed by a C-terminal transmembrane region [interpro:IPR000832] PMID:22333914. The N-terminal subdomain A of the GAIN domain is composed of a variable number of α-helices (6, 5 or 3). The ~320-residue GAIN domain is an ancient domain that exists in primitive ancestor organisms, and is conserved in all aGPCRs and all PKD1-related proteins. Functionally, the GAIN domain is both necessary and sufficient for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment. In contrast to most other autoproteolytic domains that cause the release of the cleaved mature protein, autoproteolysis of the GAIN domain does not lead to the dissociation of the cleaved extracellular sequences containing the GAIN domain from the membrane-embedded regions of the protein. The GAIN domain forms a tightly associated heterodimer upon proteolysis. Cleavage at the GAIN domain is not a feature that all GAIN domain-containing receptors possess and the GAIN domain likely has other functions (such as interacting with ligands or transmembrane helices) in addition to the autoproteolysis function.
10 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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