PROSITE documentation PDOC52057GTP-binding protein-like domain (GLD) profile
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PURL: https://purl.expasy.org/prosite/documentation/PDOC52057
The ADP-ribosylation factor (Arf) family of small GTPases, which belong to the larger Ras superfamily (see <PDOC51417>), are involved in many cellular events such as membrane trafficking, actin cytoskeleton dynamics and neurite outgrowth, as well as cell adhesion and cell migration. The function of Arfs depends on the cycle of GTP binding and hydrolysis, which are driven by guanine nucleotide-exchange factors (Arf GEFs) and Arf GTPase-activating proteins (Arf GAPs) (see<PDOC50115>), respectively.
The AGAPs (for Arf GAP with GTP-binding protein-like, ANK repeat and PH domains) are Arf GAPs characterized by their chimeric protein domain architecture consisting of a pleckstrin homology (PH) domain (see <PDOC50003>), an Arf-GAP (with a zinc-binding motif) domain (see <PDOC50115>), Ankyrin (Ank) repeats (see <PDOC50088>) as well as a GTP-binding protein-like (GLD) domain. Owing to the sequence similarity of the GLD to the classical GTPase family and the presence of an Arf-GAP domain, it has been assumed that GLDs are functionally GTPases. However, the efficient hydrolysis of GTP, ATP, UTP and CTP shows that GLD should be classified not as a GTPase but as an NTPase [1,2,3].
The overall structure of the GLD resembles that of small GTPases. The domain adopts a classical nucleotide-binding fold consisting of a six-stranded β-sheet surrounded by five α-helices (see <PDB:2BMJ>. The five α-helices (H1-H5) and six β-strands (B1-B6) connect with a B1-H1-B2-B3-H2-B4-H3-B5-H4-B6-H5 topology. The GLD shares moderate sequence identity with the Ras and Rab subfamily members of small GTPases, thus rendering the classification of the GLD unclear [1,2,3].
The profile we developed covers the entire GLD.
Last update:February 2025 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Nie Z. Stanley K.T. Stauffer S. Jacques K.M. Hirsch D.S. Takei J. Randazzo P.A. |
| Title | AGAP1, an endosome-associated, phosphoinositide-dependent ADP-ribosylation factor GTPase-activating protein that affects actin cytoskeleton. | |
| Source | J. Biol. Chem. 277:48965-48975(2002). | |
| PubMed ID | 12388557 | |
| DOI | 10.1074/jbc.M202969200 |
| 2 | Authors | Soundararajan M. Yang X. Elkins J.M. Sobott F. Doyle D.A. |
| Title | The centaurin gamma-1 GTPase-like domain functions as an NTPase. | |
| Source | Biochem. J. 401:679-688(2007). | |
| PubMed ID | 17037982 | |
| DOI | 10.1042/BJ20060555 |
| 3 | Authors | Cheng N. Zhang H. Zhang S. Ma X. Meng G. |
| Title | Crystal structure of the GTP-binding protein-like domain of AGAP1. | |
| Source | Acta Crystallogr. F. Struct. Biol. Commun. 77:105-112(2021). | |
| PubMed ID | 33830075 | |
| DOI | 10.1107/S2053230X21003150 |
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