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
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]


  • p19 (116 amino acids)


  • 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 .


  • 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):

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[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

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]


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


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]

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