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Protein

Protein Rev

Gene

rev

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate PCV12) (HIV-1)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Host-virus interaction, mRNA transport, Transport

Keywords - Ligandi

RNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Protein Rev
Alternative name(s):
ART/TRS
Anti-repression transactivator
Regulator of expression of viral proteins
Gene namesi
Name:rev
OrganismiHuman immunodeficiency virus type 1 group M subtype B (isolate PCV12) (HIV-1)
Taxonomic identifieri11679 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

Pathology & Biotechi

Keywords - Diseasei

AIDS

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 116116Protein RevPRO_0000085252Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei5 – 51Phosphoserine; by host CK2By similarity
Modified residuei8 – 81Phosphoserine; by host CK2By similarity
Modified residuei92 – 921Phosphoserine; by hostBy similarity
Modified residuei99 – 991Phosphoserine; by hostBy similarity

Post-translational modificationi

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 (By similarity).By similarity
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 (By similarity).By similarity

Keywords - PTMi

Methylation, Phosphoprotein

Interactioni

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 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
UBCP0CG482EBI-7061954,EBI-3390054From a different organism.

Protein-protein interaction databases

IntActiP04325. 1 interaction.
MINTiMINT-3973985.

Structurei

3D structure databases

DisProtiDP00424.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni18 – 269HomomultimerizationBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi34 – 5017Nuclear localization signal and RNA-binding (RRE)By similarityAdd
BLAST
Motifi73 – 8412Nuclear export signal and binding to XPO1By similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi38 – 5013Poly-ArgAdd
BLAST

Domaini

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 (By similarity).By similarity

Sequence similaritiesi

Belongs to the HIV-1 REV protein family.Curated

Family and domain databases

InterProiIPR000625. REV_protein.
[Graphical view]
PfamiPF00424. REV. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P04325-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGRSGDSDE ELLKAVRLIK FLYQSNPPPN PEGTRQARRN RRRRWRERQR
60 70 80 90 100
QIHSISERIL STYLGRSAEP VPLQLPPLER LTLDCNEDCG TSGTQGVGSP
110
QILVESPTIL ESGAKE
Length:116
Mass (Da):13,065
Last modified:August 13, 1987 - v1
Checksum:iEFAB7E6EA247EF8F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M11840 Genomic RNA. Translation: AAA45000.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M11840 Genomic RNA. Translation: AAA45000.1.

3D structure databases

DisProtiDP00424.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP04325. 1 interaction.
MINTiMINT-3973985.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

InterProiIPR000625. REV_protein.
[Graphical view]
PfamiPF00424. REV. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Three novel genes of human T-lymphotropic virus type III: immune reactivity of their products with sera from acquired immune deficiency syndrome patients."
    Arya S.K., Gallo R.C.
    Proc. Natl. Acad. Sci. U.S.A. 83:2209-2213(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "A second post-transcriptional trans-activator gene required for HTLV-III replication."
    Sodroski J., Goh W.C., Rosen C., Dayton A., Terwilliger E., Haseltine W.A.
    Nature 321:412-417(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  3. Cited for: REVIEW.

Entry informationi

Entry nameiREV_HV112
AccessioniPrimary (citable) accession number: P04325
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: August 13, 1987
Last modified: October 14, 2015
This is version 90 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

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).

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.