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Protein

Protein Rev

Gene

rev

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate HXB3) (HIV-1)
Status
Reviewed-Annotation score: Annotation score: 5 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.3 Publications

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 HXB3) (HIV-1)
Taxonomic identifieri11707 [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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi4 – 5RS → DL: Partial loss of expression of unspliced viral transcripts. No effect on phosphorylation. 1 Publication2
Mutagenesisi8 – 9SD → DL: No effect on expression of unspliced viral transcripts. Decreased phosphorylation. No effect on subcellular location. 1 Publication2
Mutagenesisi17R → D: No effect on expression of unspliced viral transcripts. No effect on phosphorylation. Expressed in nucleus and slightly in cytoplasm. 1 Publication1
Mutagenesisi23 – 26YQSN → DQDL: Complete loss of expression of unspliced viral transcripts. No effect on phosphorylation. Expressed in nucleus and slightly in cytoplasm. 1 Publication4
Mutagenesisi38 – 39RR → DL: Complete loss of expression of unspliced viral transcripts. Decreased phosphorylation. Expressed in cytoplasm and slightly in nucleus. 1 Publication2
Mutagenesisi41 – 44RRRR → DL: Complete loss of expression of unspliced viral transcripts. Complete loss of phosphorylation. Expressed in cytoplasm and slightly in nucleus. 1 Publication4
Mutagenesisi54 – 56SIS → I: Complete loss of expression of unspliced viral transcripts. No effect on phosphorylation. Expressed in nucleus and slightly in cytoplasm. 1 Publication3
Mutagenesisi61 – 62ST → DL: No effect on expression of unspliced viral transcripts. No effect on phosphorylation. Expressed in nucleus and slightly in cytoplasm. 1 Publication2
Mutagenesisi67 – 68SA → DL: No effect on expression of unspliced viral transcripts. No effect on phosphorylation. No effect on subcellular location. 1 Publication2
Mutagenesisi78 – 79LE → DL: Complete loss of expression of unspliced viral transcripts. No effect on phosphorylation. No effect on subcellular location. 1 Publication2
Mutagenesisi91 – 92TS → DL: No effect on expression of unspliced viral transcripts. No effect on phosphorylation. No effect on subcellular location. 1 Publication2
Mutagenesisi92S → R: Decreased phosphorylation. 1 Publication1
Mutagenesisi99 – 100SP → DL: No effect on expression of unspliced viral transcripts. Decreased phosphorylation. No effect on subcellular location. 1 Publication2
Mutagenesisi99S → I: Decreased phosphorylation. 1 Publication1
Mutagenesisi106 – 109SPTI → DLTV: No effect on expression of unspliced viral transcripts. No effect on phosphorylation. No effect on subcellular location. 1 Publication4
Mutagenesisi106S → F: Almost no effect on phosphorylation. 1 Publication1
Mutagenesisi112 – 113SG → DL: No effect on expression of unspliced viral transcripts. No effect on phosphorylation. No effect on subcellular location. 1 Publication2
Mutagenesisi112S → L: Almost no effect on phosphorylation. 1 Publication1

Keywords - Diseasei

AIDS

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000852621 – 116Protein RevAdd BLAST116

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei5Phosphoserine; by host CK2By similarity1
Modified residuei8Phosphoserine; by host CK2By similarity1
Modified residuei92Phosphoserine; by host1 Publication1
Modified residuei99Phosphoserine; by host1 Publication1

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

PTM databases

iPTMnetiP69718.

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.12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
gag-polP045858EBI-8540156,EBI-3989067From a different organism.

Protein-protein interaction databases

DIPiDIP-61764N.
IntActiP69718. 1 interactor.
MINTiMINT-8053053.

Structurei

Secondary structure

1116
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi11 – 24Combined sources14
Helixi35 – 63Combined sources29
Helixi65 – 67Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3LPHX-ray2.50A/B/C/D1-70[»]
4PMIX-ray3.20B/C1-70[»]
SMRiP69718.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni18 – 26Homomultimerization9

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi34 – 50Nuclear localization signal and RNA-binding (RRE)3 PublicationsAdd BLAST17
Motifi73 – 84Nuclear export signal and binding to XPO1Add BLAST12

Compositional bias

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

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.

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.

P69718-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGRSGDSDE DLLKAVRLIK FLYQSNPPPN PEGTRQARRN RRRRWRERQR
60 70 80 90 100
QIHSISERIL STYLGRSAEP VPLQLPPLER LTLDCNEDCG TSGTQGVGSP
110
QILVESPTIL ESGAKE
Length:116
Mass (Da):13,051
Last modified:August 13, 1987 - v1
Checksum:iF3DA2E7AF302FBDF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14100 Genomic RNA. Translation: AAA44677.1.
PIRiS33983.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14100 Genomic RNA. Translation: AAA44677.1.
PIRiS33983.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3LPHX-ray2.50A/B/C/D1-70[»]
4PMIX-ray3.20B/C1-70[»]
SMRiP69718.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-61764N.
IntActiP69718. 1 interactor.
MINTiMINT-8053053.

PTM databases

iPTMnetiP69718.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

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

Entry informationi

Entry nameiREV_HV1H3
AccessioniPrimary (citable) accession number: P69718
Secondary accession number(s): P04617
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: November 2, 2016
This is version 65 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).

Keywords - Technical termi

3D-structure

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.