ArfGAPs: Not Only for the Termination - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 250

Fig. 11.1 Phylogenetic tree of ArfGAP proteins in the human genome. Thirty-one human genes
have been identified that encode proteins bearing the GAP domain for Arf-GTPases

structure and function of ArfGAP-family members (see Fig. 11.1 ), and discuss
possible revised models of the functions of some ArfGAPs.

11.2 ArfGAP1 Subfamily

In the budding yeast Saccharomyces cerevisiae , six proteins possess the conserved
ArfGAP domain, and four of these family members have proven ArfGAP functions
(Poon et al. 1996 , 1999 ; Zhang et al. 2003 ). The Gcs1 and Glo3 members of the
yeast ArfGAP family are the most extensively characterized. These ArfGAP pro-
teins have partially overlapping functions in retrograde transport from the Golgi to
the endoplasmic reticulum (ER) (Poon et al. 1999 ).
ArfGAP1 is the mammalian ortholog of yeast Gsc1p (Cukierman et al. 1995 ).
ArfGAP1 functions at the Golgi by promoting the hydrolysis of GTP bound to Arf1
(Liu et al. 2005 ). ArfGAP has a zinc-finger structure that is required for GAP
activity, near its N-terminus (Ireland et al. 1994 ). A region C-terminal to the
ArfGAP domain contains two ArfGAP1 Lipid Packing Sensor (ALPS) motifs.
This motif forms an amphipathic -helix that differs from the classical one and

contains abundant serine and threonine residues on its polar surface, and thereby
appears to be able to act as a sensor that recognizes degree of the membrane
curvatures in order to determine the timing of hydrolysis of GTP-Arf1 on budding

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