| Primary Identifier | IPR044732 | Type | Domain |
| Short Name | ArfGAP_SMAP1-like |
| description | This entry represents the ArfGAP domain found in stromal membrane-associated protein 1 (SMAP1) and related proteins. SMAP1 binds to clathrin heavy chain molecules and is involved in the trafficking of clathrin-coated vesicles and preferentially exhibits GAP toward Arf6. SMAP1 is involved in Arf6-dependent vesicle trafficking, but not Arf6-mediated actin cytoskeleton reorganization, and regulates clathrin-dependent endocytosis of the transferrin receptors and E-cadherin []. This entry also includes the uncharacterised protein C824.09c from Schizosaccharomyces pombe, a predicted GTPase activating protein.Proteins containing this domain include ARF1-directed GTPase-activating protein, the cycle control GTPase activating protein (GAP) GCS1 which is important for the regulation of the ADP ribosylation factor ARF, a member of the Ras superfamily of GTP-binding proteins []. The GTP-bound form of ARF is essential for the maintenance of normal Golgi morphology, it participates in recruitment of coat proteins which are required for budding and fission of membranes. Before the fusion with an acceptor compartment the membrane must be uncoated. This step required the hydrolysis of GTP associated to ARF. These proteins contain a characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) which displays some similarity to the C4-type GATA zinc finger. The ARFGAP domain display no obvious similarity to other GAP proteins.The 3D structure of the ARFGAP domain of the PYK2-associated protein beta has been solved []. It consists of a three-stranded β-sheet surrounded by 5 alpha helices. The domain is organised around a central zinc atom which is coordinated by 4 cysteines. The ARFGAP domain is clearly unrelated to the other GAP proteins structures which are exclusively helical. Classical GAP proteins accelerate GTPase activity by supplying an arginine finger to the active site. The crystal structure of ARFGAP bound to ARF revealed that the ARFGAP domain does not supply an arginine to the active site which suggests a more indirect role of the ARFGAP domain in the GTPase hydrolysis []. |
