REV - ART/TRS Anti-repression transactivator protein
upregulates expression of Gag, Pol and Env, while downregulating itself and Tat.
Early timing of expression.
is produced from fully-spliced mRNA. Rev
binds to a 240-base
region of RNA secondary structure, the Rev RRE
RRE is located within the second intron of HIV
RRE is a "bubble" within a double-stranded RNA helix containing
non-Watson/Crick G-G base-pairing
is located on Stem Loop 2 of high affinity binding site Rev RRE
. Normally, RNA that contains
introns (unspliced or incompletely spliced RNA)
is retained in the nucleus.
-mediated export of
viral RNA is through a pathway used by Rev small nuclear RNA (snRNA) and ribosomal 5s
RNA rather than the pathway normally used by cellular mRNA.
export is mediated
through interactions with the Rev NES receptor . CRM1 The ability of
to decrease the rate of viral RNA splicing generates a negative feedback loop,
regulating its own expression
may exist as a Rev homo-tetramer
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
Rev Function & Host-Virus Protein Interactions: [ TOP]
Interactions highlighted in the image:
Potential interactions (not in the image):
Genomic Location & Protein Sequence: [ TOP]
(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]
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 -
Rev contains at least THREE functional domains
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:
3 potential sites
GTrqAR (33 - 38)
GTylGR (61 - 66)
GTsgTQ (90 - 95)
Protein kinase C:
2 potential sites
TvR (15 - 17)
SeR (56 - 58)
Casein kinase II:
3 potential sites
SdeE (8 - 11)
SisE (54 - 57)
TvlE (108 - 111)
cAMP / cGMP kinase:
Cell attachment motif:
Asp Protease motif:
Asp Prot Retro motif:
1 potential site
(35 - 50)
Zinc-finger CCHC motif:
Leucine Zipper motif:
Primary and Secondary Database Entries: [ TOP]
Reviews and References: [ TOP]
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: