Domain organization of human ArfGAP subfamilies and structure of the ArfGAP domain. (A) Representative domain structures of each human ArfGAP subfamily are depicted and are drawn to scale. Abbreviations are: ALPS, ArfGAP1 lipid-packing sensor; ArfGAP, ArfGAP domain; ANK, ankyrin repeat; BAR, Bin/Amphiphysin/Rvs; CALM, CALM binding domain; CB, clathrin-box; CC, coiled-coil; FG repeats, multiple copies of the XXFG motif; GLD, GTP-binding protein-like domain; PBS, Paxillin binding site; PH, pleckstrin homology domain; Pro(PxxP)3, cluster of three Proline-rich (PxxP) motifs; Pro(D/ELPPKP)8, eight tandem Proline-rich (D/ELPPKP) motifs; RA, Ras association motif; RhoGAP, RhoGAP domain; SAM, sterile α-motif; SH3, Src homology 3 domain; SHD, Spa-homology domain. Notes: (1) SMAP2 has CALM BD, but SMAP1 does not. (2) ASAP1 contains the indicated Pro-rich domains; ASAP2 and ASAP3 lack the Pro (D/ELPPKP) repeat and ASAP3 does not have an SH3 domain. (3) AGAP2 has a splice variant with three N-terminal PxxP motifs, called PIKE-L. (B) The structure of the isolated ArfGAP domain of human ArfGAP1 (residues 6–120) is displayed with the backbone shown in green with secondary structures indicated. The side chains of only the conserved arginine (Arg50, on the right) and the four zinc finger cysteines (center; Cys22, 25, 42, and 45) are displayed along with the coordinated Zn2+ (gray sphere). This image was generated using PyMol.