Target Information
Target General Information | Top | |||||
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Target ID |
T00420
(Former ID: TTDI02157)
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Target Name |
Human immunodeficiency virus Rev protein (HIV rev)
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Synonyms |
rev; Regulator of expression of viral proteins; Anti-repression transactivator; ART/TRS
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Gene Name |
HIV rev
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Human immunodeficiency virus disease [ICD-11: 1C60-1C62] | |||||
Function |
Escorts unspliced or incompletely spliced viral pre- mRNAs (late transcripts) out of the nucleus of infected cells. These pre-mRNAs carry a recognition sequence called Rev responsive element (RRE) located in the env gene, that is not present in fully spliced viral mRNAs (early transcripts). This function is essential since most viral proteins are translated from unspliced or partially spliced pre-mRNAs which cannot exit the nucleus by the pathway used by fully processed cellular mRNAs. Rev itself is translated from a fully spliced mRNA that readily exits the nucleus. Rev's nuclear localization signal (NLS) bindsdirectly to KPNB1/Importin beta-1 without previous binding to KPNA1/Importin alpha-1. KPNB1 binds to the GDP bound form of RAN (Ran-GDP) and targets Rev to the nucleus. In the nucleus, the conversionfrom Ran-GDP to Ran-GTP dissociates Rev from KPNB1 and allows Rev's binding to the RRE in viral pre-mRNAs. Rev multimerization on the RRE via cooperative assembly exposes its nuclear export signal (NES) to the surface. Rev can then form a complex with XPO1/CRM1 and Ran-GTP, leading to nuclear export of the complex. Conversion from Ran-GTP to Ran-GDP mediates dissociation of the Rev/RRE/XPO1/RAN complex, so that Rev can return to the nucleus for a subsequent round of export. Beside KPNB1, also seems to interact with TNPO1/Transportin-1, RANBP5/IPO5 and IPO7/RANBP7 for nuclear import. The nucleoporin-like HRB/RIP is an essential cofactor that probably indirectly interacts with Rev to release HIV RNAs from the perinuclear region to the cytoplasm. Interacts with DDX1; the interaction is necessary for proper subcellular localization of this protein.
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UniProt ID | ||||||
Sequence |
MAGRSGDSDEELIRTVRLIKLLYQSNPPPNPEGTRQARRNRRRRWRERQRQIHSISERIL
GTYLGRSAEPVPLQLPPLERLTLDCNEDCGTSGTQGVGSPQILVESPTVLESGTKE Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
1 | Ad35-GRIN/ENV | Drug Info | Phase 1 | Human immunodeficiency virus infection | [2] | |
2 | ATI-0917 | Drug Info | Phase 1 | Human immunodeficiency virus infection | [1] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 1 Inhibitor drugs | + | ||||
1 | ATI-0917 | Drug Info | [1] |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
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There is no similarity protein (E value < 0.005) for this target
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Chemical Structure based Activity Landscape of Target | Top |
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Target Affiliated Biological Pathways | Top | |||||
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Reactome | [+] 13 Reactome Pathways | + | ||||
1 | Uncoating of the HIV Virion | |||||
2 | Budding and maturation of HIV virion | |||||
3 | Integration of provirus | |||||
4 | Early Phase of HIV Life Cycle | |||||
5 | Minus-strand DNA synthesis | |||||
6 | Plus-strand DNA synthesis | |||||
7 | 2-LTR circle formation | |||||
8 | Binding and entry of HIV virion | |||||
9 | Assembly Of The HIV Virion | |||||
10 | Integration of viral DNA into host genomic DNA | |||||
11 | Autointegration results in viral DNA circles | |||||
12 | APOBEC3G mediated resistance to HIV-1 infection | |||||
13 | Vpr-mediated nuclear import of PICs | |||||
WikiPathways | [+] 2 WikiPathways | + | ||||
1 | Host Interactions of HIV factors | |||||
2 | HIV Life Cycle |
References | Top | |||||
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REF 1 | Antiretroviral drugs in development. A report from HIV DART 2008: Frontiers in Drug Development for Antiretroviral Therapies, 9-12 December 2008, Rio Grande, Puerto Rico. Expert Opin Investig Drugs. 2009 Apr;18(4):549-53. | |||||
REF 2 | ClinicalTrials.gov (NCT01496989) Safety and Immunogenicity Study of HIV-MAG Vaccine +/- IL-12 and Ad35-GRIN/ENV in HIV-uninfected Volunteers. U.S. National Institutes of Health. | |||||
REF 3 | A phase I double blind, placebo-controlled, randomized study of a multigenic HIV-1 adenovirus subtype 35 vector vaccine in healthy uninfected adults. PLoS One. 2012;7(8):e41936. |
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