Monoubiquitination of N-myristoyl GAG (P12493) protein

Stable Identifier
R-HSA-1169307
Type
Reaction [omitted]
Species
Homo sapiens
Related Species
Human immunodeficiency virus 1
Compartment
cytosol
ReviewStatus
5/5
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Monoubiquitination of N-myristoyl GAG (P12493) protein
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Over expression of ISG15 inhibits the release of HIV-1 virions. ISG15 inhibits the ubiquitination of viral GAG and host Tsg101 proteins and disrupts their interaction, thereby preventing assembly and release of virions. Cytosolic N-myristoyl Gag polyprotein is conjugated with a single molecule of ubiquitin. Conjugation is typically to one of two lysine residues in the p6 domain of Gag but can be to lysine residues in the MA, CA, NC, and SP2 domains of the protein. The specific host cell E2 and E3 proteins that mediate Gag ubiquitination have not been identified. The same studies that first identified the p6 ubiquitination sites in Gag also called the biological significance of Gag ubiquitination into question by demonstrating that Gag proteins in which the p6 ubiquitination sites had been removed by mutagenesis could still assemble efficiently into infectious viral particles (Ott et al. 1998, 2000). Later work, however, identified additional ubiquitination sites throughout the C-terminal region of the Gag polyprotein, and when all of these sites are removed by mutagenesis, both viral assembly involving the mutant Gag polyprotein and infectivity of the resulting viral particles are sharply reduced (Gottwein et al. 2006).
Literature References
PubMed ID Title Journal Year
9525617 Ubiquitin is covalently attached to the p6Gag proteins of human immunodeficiency virus type 1 and simian immunodeficiency virus and to the p12Gag protein of Moloney murine leukemia virus

Ott, DE, Coren, LV, Oroszlan, S, Yoshinaka, Y, Henderson, LE, Johnson, DG, Arthur, LO, Sowder RC, 2nd, Kane, BP, Copeland, TD

J Virol 1998
16775314 Cumulative mutations of ubiquitin acceptor sites in human immunodeficiency virus type 1 gag cause a late budding defect

Habermann, A, Jager, S, Gottwein, E, Krausslich, HG

J Virol 2006
11112487 Ubiquitination of HIV-1 and MuLV Gag

Ott, DE, Coren, LV, Gagliardi, TD, Chertova, EN, Schubert, U

Virology 2000
Participants
Input
Output
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as an event of
This event is regulated
Negatively by
Regulator
ISG15 [cytosol] (Homo sapiens)
Authored
Garapati, P V  (2011-01-18)
Reviewed
Zhang, DE  (2011-02-11)
Created
Garapati, P V  (2011-01-18)
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