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Protein Rev



Human immunodeficiency virus type 1 group M subtype B (isolate CDC-451) (HIV-1)
Reviewed-Annotation score: -Protein inferred from homologyi


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) binds directly 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 conversion from 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.UniRule annotation


HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).UniRule annotation

GO - Molecular functioni

GO - Biological processi


Molecular functionRNA-binding
Biological processHost-virus interaction, mRNA transport, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Protein RevUniRule annotation
Alternative name(s):
ART/TRSUniRule annotation
Anti-repression transactivatorUniRule annotation
Regulator of expression of viral proteinsUniRule annotation
Gene namesi
Name:revUniRule annotation
OrganismiHuman immunodeficiency virus type 1 group M subtype B (isolate CDC-451) (HIV-1)
Taxonomic identifieri11687 [NCBI]
Taxonomic lineageiVirusesOrterviralesRetroviridaeOrthoretrovirinaeLentivirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

Pathology & Biotechi

Keywords - Diseasei


PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000852611 – 116Protein RevAdd BLAST116

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei5Phosphoserine; by host CK2UniRule annotation1
Modified residuei8Phosphoserine; by host CK2UniRule annotation1
Modified residuei92Phosphoserine; by hostUniRule annotation1
Modified residuei99Phosphoserine; by hostUniRule annotation1

Post-translational modificationi

Asymmetrically arginine dimethylated at one site by host PRMT6. Methylation impairs the RNA-binding activity and export of viral RNA from the nucleus to the cytoplasm.UniRule annotation
Phosphorylated by protein kinase CK2. Presence of, and maybe binding to the N-terminus of the regulatory beta subunit of CK2 is necessary for CK2-mediated Rev's phosphorylation.UniRule annotation

Keywords - PTMi

Methylation, Phosphoprotein


Subunit structurei

Homomultimer; when bound to the RRE. Multimeric assembly is essential for activity and may involve XPO1. Binds to human KPNB1, XPO1, TNPO1, RANBP5 and IPO7. Interacts with the viral Integrase. Interacts with human KHDRBS1. Interacts with human NAP1; this interaction decreases Rev multimerization and stimulates its activity. Interacts with human DEAD-box helicases DDX3 and DDX24; these interactions may serve for viral RNA export to the cytoplasm and packaging, respectively. Interacts with human PSIP1; this interaction may inhibit HIV-1 DNA integration by promoting dissociation of the Integrase-LEDGF/p75 complex.UniRule annotation

Protein-protein interaction databases



3D structure databases


Family & Domainsi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni18 – 26HomomultimerizationUniRule annotation9


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi34 – 50Nuclear localization signal and RNA-binding (RRE)UniRule annotationAdd BLAST17
Motifi73 – 84Nuclear export signal and binding to XPO1UniRule annotationAdd BLAST12

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi38 – 50Poly-ArgAdd BLAST13


The RNA-binding motif binds to the RRE, a 240 bp stem-and-loop structure present in incompletely spliced viral pre-mRNAs. This region also contains the NLS which mediates nuclear localization via KPNB1 binding and, when the N-terminal sequence is present, nucleolar targeting. These overlapping functions prevent Rev bound to RRE from undesirable return to the nucleus. When Rev binds the RRE, the NLS becomes masked while the NES remains accessible. The leucine-rich NES mediates binding to human XPO1.UniRule annotation

Sequence similaritiesi

Belongs to the HIV-1 REV protein family.UniRule annotation

Family and domain databases

HAMAPiMF_04077 REV_HIV1, 1 hit
InterProiView protein in InterPro
IPR000625 REV_protein
PfamiView protein in Pfam
PF00424 REV, 1 hit


Sequence statusi: Complete.

P05865-1 [UniParc]FASTAAdd to basket
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Mass (Da):12,998
Last modified:November 1, 1988 - v1

Sequence databases

Select the link destinations:
Links Updated
M13137 Genomic RNA Translation: AAA44310.1

Similar proteinsi


Sequence databases

Select the link destinations:
Links Updated
M13137 Genomic RNA Translation: AAA44310.1

3D structure databases


Protein-protein interaction databases


Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

HAMAPiMF_04077 REV_HIV1, 1 hit
InterProiView protein in InterPro
IPR000625 REV_protein
PfamiView protein in Pfam
PF00424 REV, 1 hit

Entry informationi

Entry nameiREV_HV1C4
AccessioniPrimary (citable) accession number: P05865
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: September 12, 2018
This is version 91 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program



  1. SIMILARITY comments
    Index of protein domains and families
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Main funding by: National Institutes of Health

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