REV - ART/TRS Anti-repression transactivator protein

HIV REV upregulates expression of Gag, Pol and Env, while downregulating itself and Tat.




PDB-1ETF: HIV-1 (isolate UNKNOWN) Rev Response Element RNA (Chain A) and HIV-1 Rev peptide (Chain B) - produced using SwissModel/SPDBV/POVray

Key web links:
ViralZone: HIV-1, HIV replication cycle, HIV resource
PDB: 1ETF (HIV-1 REV)
UniProt: P04618 (HIV-1 HXB2 REV)
Chime Tutorial: not available
HIV-1/Human Protein Interaction DB: HIV-1 Rev
Los Alamos HIV structure DB: not available
EMBL: K03455 [EMBL/GenBank/DDBJ]


Isoforms:

  • p19 (116 amino acids)

Function:

  • Binds to the Rev Response Element (RRE) to facilitate the export of unspliced or incompletely spliced viral RNAs out of the nucleus and to the cytoplasm .
  • Upregulates the expression of HIV structural genes (gag, pol, env).
  • Downregulates the expression of HIV regulatory genes (rev, tat).
  • Sequence-specific RNA-binding protein .
  • Transports genomic transcripts from the nucleus to cytoplasm.
  • Induces the transition from early to late phase of HIV gene expression .

Localization:

  • Cell nucleolus/nucleus
  • Cell cytoplasm [shuttling between nucleolus and cytoplasm]

Additional Information:

  • Early timing of expression.
  • Rev is produced from fully-spliced mRNA.
  • Rev binds to a 240-base region of RNA secondary structure, the RRE .
  • The RRE is located within the second intron of HIV .
  • The RRE is a "bubble" within a double-stranded RNA helix containing non-Watson/Crick G-G base-pairing .
  • Rev high affinity binding site is located on Stem Loop 2 of RRE .
  • Normally, RNA that contains introns (unspliced or incompletely spliced RNA) is retained in the nucleus.
  • Rev-mediated export of viral RNA is through a pathway used by small nuclear RNA (snRNA) and ribosomal 5s RNA rather than the pathway normally used by cellular mRNA.
  • Rev export is mediated through interactions with the NES receptor CRM1.
  • The ability of Rev to decrease the rate of viral RNA splicing generates a negative feedback loop, regulating its own expression .
  • Rev may exist as a homo-tetramer in solution .
  • Rev is required for HIV-1 replication; infected cells that lack Rev activity contain transcriptionally active viral genomes, but do not express viral late phase genes that are necessary for viral particle formation.

Rev Function & Host-Virus Protein Interactions:[TOP]




Interactions highlighted in the image:


Potential interactions (not in the image):



Genomic Location & Protein Sequence: [TOP]

HIV-1 (HXB2):

          10         20         30         40         50         60         70         80         90        100
| | | | | | | | | |
MAGRSGDSDE ELIRTVRLIK LLYQSNPPPN PEGTRQARRN RRRRWRERQR QIHSISERIL GTYLGRSAEP VPLQLPPLER LTLDCNEDCG TSGTQGVGSP
110
|
QILVESPTVL ESGTKE
[download in fasta format]

Length: 116 amino acids
Molecular Weight: 13075 Da
Theoretical pI: 9.29
Gene Description: Rev is encoded by two exons.


Protein Domains/Folds/Motifs: [TOP]

InterPro signature for Anti-repression trans-activator protein, REV protein - IPR000625

  • Rev contains at least THREE functional domains .
  • An arginine-rich RNA binding-domain mediates interactions with RRE.
  • A multimerization domain is required for Rev to function .
  • Rev has an effector domain, which is a specific Nuclear Export Signal (NES) .

Secondary Structure prediction:

Low Complexity Regions - seg:


Antigenic Sites - EMBOSS:

Predicted Motifs: Printer-friendly version

N-glycosylation:
N-myristoylation:
Amidation:
Protein kinase C:
Casein kinase II:
Tyrosine kinase:
cAMP / cGMP kinase:
Cell attachment motif:
Asp Protease motif:
Asp Prot Retro motif:
Arginine-rich Region:
Cysteine-rich Region:
Tryptophan-rich Region:
Zinc-finger CCHC motif:
Leucine Zipper motif:

Primary and Secondary Database Entries: [TOP]

Identifiers:



ViralZone: HIV-1, HIV replication cycle, HIV resource
PDB/MMDB: Search for HIV-1 & REV

UniProt: P04618 (HIV-1 HXB2 REV)
EMBL: K03455; AAB50257.1 [EMBL/GenBank/DDBJ]

InterPro: IPR000625
Pfam: PF00424
Prints: none
SCOP: SSF48726 Immunoglobin
BLOCKS: P04618
Prosite: P04618
ProtoNet: P04618
Database of Interacting Proteins: P04618
ModBase: P04618
HIV-1/Human Protein Interaction DB: HIV-1 Rev
HIV-1 Sequence Database Los Alamos HIV Sequence Database

PDB:




Reviews and References: [TOP]


Cite the resource by citing the following paper:
Doherty R et al. BioAfrica's HIV-1 Proteomics Resource: Combining protein data with bioinformatics tools. Retrovirology (2005), 9;2(1):18.

1 - HIV Sequence Compendium 2000
Kuiken CL, Foley B, Hahn B, Korber B, Marx PA, McCutchan F, Mellors JW, Mullins JI, Sodroski J, Wolinksy S.
Theoretical Biol. & Biophys. Group, Los Alamos Nat Lab, LA-UR 01-3860 [Read it online: Compendium]
2 - Retroviruses
Coffin JM, Hughes SH, Varmus HE.
CD-ROM ed. (2002) Cold Spring Harbor Laboratory Press [Read it online: NCBI Bookshelf]
3 - Sequence-specific RNA binding by the HIV-1 Rev protein.
Zapp ML, Green MR, Szostak JW.
Nature 342: 714-716 (1989) [pubmed: 2556643]
4 - Temporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection:
Evidence for differential gene expression.
Kim SY, Byrn R, Groopman J.
J Virol 63: 3708-3713 (1989) [pubmed: 2760980]
5 - The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear
export of unspliced viral mRNA.
Malim MH, Hauber J, Le SY.
Nature 338(6212): 254-257 (1989) [pubmed: 2784194]
6 - HIV-1 Rev regulation involves recognition of non-Watson-Crick base pairs in viral RNA.
Bartel DP, Zapp ML, Green MR.
Cell 67: 529-536 (1991) [pubmed: 1934059]
7 - Feedback regulation of human immunodeficiency virus type 1 expression by the Rev protein.
Felber BK, Drysdale CM, Pavlakis GN.
J Virol 64: 3734-3741 (1990) [pubmed: 2196381]
8 - Functional dissection of the HIV-1 Rev trans-activator: derivation of a trans-dominant
repressor of Rev function.
Malim MH, Bohnlein S, Hauber J.
Cell 58: 205-214 (1989) [pubmed: 2752419]
9 - Mutational analysis of the human immunodeficiency virus type 1 Rev transactivator:
Essential residues near the amino terminus.
Hope TJ, McDonald D, Huang XJ.
J Virol 64: 5360-5366 (1990) [pubmed: 2120472]
10 - Oligomerization and RNA binding domains of the type 1 human immunodeficiency virus Rev protein:
A dual function for an arginine-rich binding motif.
Zapp ML, Hope TJ, Parslow TG.
Proc Natl Acad Sci USA 88: 7734-7738 (1991) [pubmed: 1715576]
11 - Identification of a signal for rapid export of proteins from the nucleus.
Wen W, Meinkoth JL, Tsien RY, Taylor SS.
Cell 82: 463-473 (1995) [pubmed: 7634336]
12 - The HIV-1 Rev activation domain is a nuclear export signal that accesses an export pathway
used by specific cellular RNAs.
Fischer U, Huber J, Boelens WC.
Cell 82: 475-483 (1995) [pubmed: 7543368]
13 - The ins and outs of HIV Rev.
Hope TJ.
Arch Biochem Biophys. 15;365(2):186-91 (1999) [pubmed: 10328811]
14 - Life of psi: how full-length HIV-1 RNAs become packaged genomes in the viral particles.
Kuzembayeva M, Dilley K, Sardo L, Hu WS.
Virology 454-455:362-70 (2014) [pubmed: 24530126]
15 - The specificity of the CRM1-Rev nuclear export signal interaction is mediated by RanGTP.
Askjaer P, Jensen TH, Nilsson J, Englmeier L, Kjems J.
J Biol Chem. 273(50):33414-22 (1998) [pubmed: 9837918]
16 - Interactions between HIV Rev and nuclear import and export factors: the Rev nuclear localisation signal mediates specific binding to human importin-beta.
Henderson BR, Percipalle P.
J Mol Biol. 274(5):693-707 (1997) [pubmed: 9405152]
17 - Specific complex of human immunodeficiency virus type 1 rev and nucleolar B23 proteins: dissociation by the Rev response element.
Fankhauser C, Izaurralde E, Adachi Y, Wingfield P, Laemmli UK.
Mol Cell Biol. 11(5):2567-75 (1991) [pubmed: 2017166]
18 - Distinct DDX DEAD-box RNA helicases cooperate to modulate the HIV-1 Rev function.
Yasuda-Inoue M, Kuroki M, Ariumi Y.
Biochem Biophys Res Commun. 434(4):803-8 (2013) [pubmed: 23608157]
19 - Sam68 is absolutely required for Rev function and HIV-1 production.
Modem S, Badri KR, Holland TC, Reddy TR.
Nucleic Acids Res. 33(3):873-9 (2005) [pubmed: 15701759]
20 - 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 RJ.
Virology 330(2):471-80 (2004) [pubmed: 15567440]
21 - DDX5 facilitates HIV-1 replication as a cellular co-factor of Rev.
Zhou X, Luo J, Mills L, Wu S, Pan T, Geng G, Zhang J, Luo H, Liu C, Zhang H.
PLoS One 8(5):e65040 (2013) [pubmed: 23741449]
22 - The requirement of the DEAD-box protein DDX24 for the packaging of human immunodeficiency virus type 1 RNA.
Ma J, Rong L, Zhou Y, Roy BB, Lu J, Abrahamyan L, Mouland AJ, Pan Q, Liang C.
Virology 375(1):253-64 (2008) [pubmed: 18289627]



Thanks to ViralZone at the Swiss Institute of Bioinformatics (SIB) for allowing the use of their images on bioafrica.net.
Page last updated by Megan Druce, Paula Sommer and Tulio de Oliveira (UKZN/Africa Centre) & Philippe Le Mercier, Chantal Hulo and Patrick Masson (SIB/ViralZone).