PROSITE documentation PDOC51716
IRG-type guanine nucleotide-binding (G) domain profile


The P-loop (see <PDOC00017>) guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides.

The p47 or immunity-related GTPases (IRG) are at least as old as the vertebrates. The IRG proteins are an essential resistance system in the mouse for immunity against pathogens that enter the cell via a vacuole. Despite its importance for the mouse, the IRG resistance system is absent from humans because it has been lost during the divergent evolution of the primates. The IRG proteins appear to be accompanied phylogenetically by homologous proteins, named 'quasi IRG' (IRGQ) proteins, that probably lack nucleotide binding or hydrolysis function, and that may form regulatory heterodimers with functional IRG proteins. The region of lowest similarity is in the G domain, and conserved GTP-binding motifs are lacking [1,2,3].

The profile we developed covers the entire IRG-type G domain.

Last update:

April 2014 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

G_IRG, PS51716; IRG-type guanine nucleotide-binding (G) domain profile  (MATRIX)


1AuthorsLeipe D.D. Wolf Y.I. Koonin E.V. Aravind L.
TitleClassification and evolution of P-loop GTPases and related ATPases.
SourceJ. Mol. Biol. 317:41-72(2002).
PubMed ID11916378

2AuthorsBoehm U. Guethlein L. Klamp T. Ozbek K. Schaub A. Fuetterer A. Pfeffer K. Howard J.C.
TitleTwo families of GTPases dominate the complex cellular response to IFN-gamma.
SourceJ. Immunol. 161:6715-6723(1998).
PubMed ID9862701

3AuthorsBekpen C. Hunn J.P. Rohde C. Parvanova I. Guethlein L. Dunn D.M. Glowalla E. Leptin M. Howard J.C.
TitleThe interferon-inducible p47 (IRG) GTPases in vertebrates: loss of the cell autonomous resistance mechanism in the human lineage.
SourceGenome Biol. 6:R92-R92(2005).
PubMed ID16277747

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