ArfGAPs: Not Only for the Termination - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 255

11.7 AGFG Subfamily

The ArfGAP domain and FG repeat-containing proteins (AGFG) subfamily con-
sists of AGFG1 and AGFG2. AGFG1 was originally identified using yeast
two-hybrid screens with the HIV Rev protein (Bogerd et al. 1995 ; Fritz
et al. 1995 ), and is therefore called HIV Rev-binding protein (Hrb), Rev/Rex
activation domain-binding protein (Rab), or Rev-interacting protein (RIP).
AGFGs have an ArfGAP domain at the N-terminus, and phenylalanine-glycine
(FG) repeats at the C-terminus. The GAP domain of AGFG possesses homology
with nucleoporins and is thought to be involved in the RNA transport function of
HIV-1 Rev, possibly together with the nuclear export receptor CRM1 (Fritz
et al. 1995 ; Farjot et al. 1999 ). However, the ArfGAP activity of AGFG has not
yet been reported. The FG repeats of AGFG possess homology with that of
nucleoporins, which mediate nucleocytoplasmic transport. AGFG1 was shown to
be an essential cofactor for the Rev protein, which enhances the release of incom-
pletely spliced HIV-1 RNAs from the perinuclear region (S ´ nchez-Velar
et al. 2004 ), and also an adaptor protein that seems to be involved in some types
of clathrin-mediated membrane trafficking, via interacting with Eps15 (Salcini
et al. 1997 ), AP-2 (Schmid et al. 2006 ), or VAMP-7 (Chaineau et al. 2008 ; Pryor
et al. 2008 ).

11.8 ASAP Subfamily

This subfamily of ArfGAPs has been called by many different names, and unifica-
tion of the nomenclature was proposed more than once (Kahn 2003 ; Kahn
et al. 2008 ). ASAP1 was also called KIAA1249, DEF1, DDEF1, centaurin 4,

and PAG2 and once proposed to be unified as AMAP1 (Kahn 2003 ). ASAP2 was
called PAG3, and PAP

β

, and once proposed to be unified as AMAP2 (Kahn 2003 ).
ASAP3 was called ACAP4 and DDEFL1. ASAP1 was originally named when it
was purified from bovine brain as a PI(4,5)P 2 -dependent GAP against Arf1 (Brown
et al. 1998 ). PAP

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was originally named as a protein that exhibits PI(4,5)P 2 -
dependent GAP activity toward Arf1 in vitro (Andreev et al. 1999 ). The specific
activity of ASAP1 toward Arf1 was also demonstrated in vivo, in which
overexpressed ASAP1 was shown to reduce cellular GTP-Arf1, but not GTP-Arf6
(Furman et al. 2002 ).
The ASAPs contain the Bin/Amphiphysin/RVS (BAR) domain, the PH domain,
the GAP domain, the ANK repeat domain, a proline-rich region (PRR), and the Src
homology 3 (SH3) domain (Brown et al. 1998 ).
The PH domain is essential for the PI(4,5)P 2 -dependent GAP activity (Kam
et al. 2000 ). GAP activity toward Arf1 or Arf5 was detectable using a truncated
recombinant protein of ASAP1, which was composed of the PH domain, the GAP

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