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P04618 (REV_HV1H2) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein Rev
Alternative name(s):
ART/TRS
Anti-repression transactivator
Regulator of expression of viral proteins
Gene names
Name:rev
OrganismHuman immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1) [Reference proteome]
Taxonomic identifier11706 [NCBI]
Taxonomic lineageVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length116 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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) 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. Interacts with DDX1; the interaction is necessary for proper subcellular localization of this protein.

Subunit structure

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. Ref.5

Subcellular location

Host nucleushost nucleolus. Host cytoplasm. Note: The presence of both nuclear import and nuclear export signals leads to continuous shuttling between the nucleus and cytoplasm By similarity.

Domain

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.

Post-translational modification

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. Ref.2 Ref.3 Ref.4

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.

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).

Sequence similarities

Belongs to the HIV-1 REV protein family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CHCHD1Q96BP23EBI-6164309,EBI-5454898From a different organism.
IKQ131233EBI-6164309,EBI-713456From a different organism.
MITD1Q8WV922EBI-6164309,EBI-2691489From a different organism.
MRPS9P829332EBI-6164309,EBI-721385From a different organism.
SSBP1Q048373EBI-6164309,EBI-353460From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 116116Protein Rev
PRO_0000085279

Regions

Region18 – 269Homomultimerization By similarity
Motif34 – 5017Nuclear localization signal and RNA-binding (RRE) By similarity
Motif73 – 8412Nuclear export signal and binding to XPO1 By similarity
Compositional bias38 – 5013Poly-Arg

Amino acid modifications

Modified residue51Phosphoserine; by host CK2 Ref.2
Modified residue81Phosphoserine; by host CK2 Ref.2
Modified residue921Phosphoserine; by host By similarity
Modified residue991Phosphoserine; by host By similarity

Sequences

Sequence LengthMass (Da)Tools
P04618 [UniParc].

Last modified August 13, 1987. Version 1.
Checksum: 4BCF5059C9A7F3B2

FASTA11613,075
        10         20         30         40         50         60 
MAGRSGDSDE ELIRTVRLIK LLYQSNPPPN PEGTRQARRN RRRRWRERQR QIHSISERIL 

        70         80         90        100        110 
GTYLGRSAEP VPLQLPPLER LTLDCNEDCG TSGTQGVGSP QILVESPTVL ESGTKE 

« Hide

References

[1]"Complete nucleotide sequences of functional clones of the AIDS virus."
Ratner L., Fisher A., Jagodzinski L.L., Mitsuya H., Liou R.-S., Gallo R.C., Wong-Staal F.
AIDS Res. Hum. Retroviruses 3:57-69(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"Phosphorylation of HIV-1 Rev protein: implication of protein kinase CK2 and pro-directed kinases."
Meggio F., D'Agostino D.M., Ciminale V., Chieco-Bianchi L., Pinna L.A.
Biochem. Biophys. Res. Commun. 226:547-554(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-5 AND SER-8 BY CK2.
[3]"Unique features of HIV-1 Rev protein phosphorylation by protein kinase CK2 ('casein kinase-2')."
Marin O., Sarno S., Boschetti M., Pagano M.A., Meggio F., Ciminale V., D'Agostino D.M., Pinna L.A.
FEBS Lett. 481:63-67(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY CK2.
[4]"HIV-1 Rev transactivator: a beta-subunit directed substrate and effector of protein kinase CK2."
Meggio F., Marin O., Boschetti M., Sarno S., Pinna L.A.
Mol. Cell. Biochem. 227:145-151(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY CK2.
[5]"A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev."
Fang J., Kubota S., Yang B., Zhou N., Zhang H., Godbout R., Pomerantz R.J.
Virology 330:471-480(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDX1.
[6]"The ins and outs of HIV Rev."
Hope T.J.
Arch. Biochem. Biophys. 365:186-191(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
K03455 Genomic RNA. Translation: AAB50257.1.
PIRJC4968.
RefSeqNP_057854.1. NC_001802.1.

3D structure databases

ProteinModelPortalP04618.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid1205542. 226 interactions.
IntActP04618. 18 interactions.

Chemistry

BindingDBP04618.
ChEMBLCHEMBL1293282.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID155908.

Enzyme and pathway databases

ReactomeREACT_116125. Disease.

Family and domain databases

InterProIPR000625. REV_protein.
[Graphical view]
PfamPF00424. REV. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameREV_HV1H2
AccessionPrimary (citable) accession number: P04618
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: April 16, 2014
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families