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Protein

Protein Rev

Gene

rev

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
Status
Reviewed-Annotation score: -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.UniRule annotation

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).UniRule annotation

GO - Molecular functioni

  • DNA-binding transcription factor activity Source: InterPro
  • identical protein binding Source: IntAct
  • RNA binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-162585 Uncoating of the HIV Virion
R-HSA-162588 Budding and maturation of HIV virion
R-HSA-162592 Integration of provirus
R-HSA-162594 Early Phase of HIV Life Cycle
R-HSA-164516 Minus-strand DNA synthesis
R-HSA-164525 Plus-strand DNA synthesis
R-HSA-164843 2-LTR circle formation
R-HSA-165054 Rev-mediated nuclear export of HIV RNA
R-HSA-173107 Binding and entry of HIV virion
R-HSA-175474 Assembly Of The HIV Virion
R-HSA-175567 Integration of viral DNA into host genomic DNA
R-HSA-177539 Autointegration results in viral DNA circles
R-HSA-180689 APOBEC3G mediated resistance to HIV-1 infection
R-HSA-180746 Nuclear import of Rev protein
R-HSA-180910 Vpr-mediated nuclear import of PICs

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 HXB2) (HIV-1)
Taxonomic identifieri11706 [NCBI]
Taxonomic lineageiVirusesOrterviralesRetroviridaeOrthoretrovirinaeLentivirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000002241 Componenti: Genome

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

Pathology & Biotechi

Keywords - Diseasei

AIDS

Chemistry databases

ChEMBLiCHEMBL1293282

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000852791 – 116Protein RevAdd BLAST116

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei5Phosphoserine; by host CK2UniRule annotation1 Publication1
Modified residuei8Phosphoserine; by host CK2UniRule annotation1 Publication1
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 annotation3 Publications

Keywords - PTMi

Methylation, Phosphoprotein

PTM databases

iPTMnetiP04618

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.UniRule annotation

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi1205542, 225 interactors
DIPiDIP-61717N
IntActiP04618, 25 interactors

Structurei

3D structure databases

ProteinModelPortaliP04618
SMRiP04618
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

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

Motif

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

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.UniRule annotation

Sequence similaritiesi

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

Phylogenomic databases

OrthoDBiVOG090001FN

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

Sequencei

Sequence statusi: Complete.

P04618-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAGRSGDSDE ELIRTVRLIK LLYQSNPPPN PEGTRQARRN RRRRWRERQR
60 70 80 90 100
QIHSISERIL GTYLGRSAEP VPLQLPPLER LTLDCNEDCG TSGTQGVGSP
110
QILVESPTVL ESGTKE
Length:116
Mass (Da):13,075
Last modified:August 13, 1987 - v1
Checksum:i4BCF5059C9A7F3B2
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K03455 Genomic RNA Translation: AAB50257.1
PIRiJC4968
RefSeqiNP_057854.1, NC_001802.1

Genome annotation databases

GeneIDi155908
KEGGivg:155908

Similar proteinsi

Cross-referencesi

Web resourcesi

BioAfrica HIV proteomics resource

Rev entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K03455 Genomic RNA Translation: AAB50257.1
PIRiJC4968
RefSeqiNP_057854.1, NC_001802.1

3D structure databases

ProteinModelPortaliP04618
SMRiP04618
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi1205542, 225 interactors
DIPiDIP-61717N
IntActiP04618, 25 interactors

Chemistry databases

ChEMBLiCHEMBL1293282

PTM databases

iPTMnetiP04618

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi155908
KEGGivg:155908

Phylogenomic databases

OrthoDBiVOG090001FN

Enzyme and pathway databases

ReactomeiR-HSA-162585 Uncoating of the HIV Virion
R-HSA-162588 Budding and maturation of HIV virion
R-HSA-162592 Integration of provirus
R-HSA-162594 Early Phase of HIV Life Cycle
R-HSA-164516 Minus-strand DNA synthesis
R-HSA-164525 Plus-strand DNA synthesis
R-HSA-164843 2-LTR circle formation
R-HSA-165054 Rev-mediated nuclear export of HIV RNA
R-HSA-173107 Binding and entry of HIV virion
R-HSA-175474 Assembly Of The HIV Virion
R-HSA-175567 Integration of viral DNA into host genomic DNA
R-HSA-177539 Autointegration results in viral DNA circles
R-HSA-180689 APOBEC3G mediated resistance to HIV-1 infection
R-HSA-180746 Nuclear import of Rev protein
R-HSA-180910 Vpr-mediated nuclear import of PICs

Miscellaneous databases

PROiPR:P04618

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
ProtoNetiSearch...

Entry informationi

Entry nameiREV_HV1H2
AccessioniPrimary (citable) accession number: P04618
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: October 10, 2018
This is version 124 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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