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
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ViralZone:HIV-1
PDB: 1ETF (HIV-1 REV)
SwissProt: P04618 (HIV-1 HXB2 REV)
Chime Tutorial: not available
Los Alamos HIV structure DB: not available
EMBL: K03455 [EMBL/GenBank/DDBJ]
BioAfrica: Rev Protein Data Mining Tool


Isoforms:

  • p19 (116 amino acids)


Localization:

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


Function:

  • Binds to RRE, which facilitates export of unspliced and incompletely spliced viral RNA from nucleus to cytoplasm (Ref. #13)
  • upregulates expression of structural genes (gag, pol, env)
  • downregulates expression of regulatory genes (rev, tat)
  • sequence-specific RNA-binding protein (Ref. #3)
  • transports genomic transcripts from nucleus to cytoplasm
  • induces the transition from early to late phase of HIV gene expression (Ref. #4)

Additional Information:

  • Rev functions early in viral infection
  • Rev is produced from fully-spliced mRNA
  • Rev binds to a 240-base region of RNA secondary structure (Rev Responsive Element) (Ref. #5)
  • The Rev Responsive Element (RRE) is located within the second intron of HIV (Ref. #5)
  • The RRE is a "bubble" within a double-stranded RNA helix containing non-Watson/Crick G-G base-pairing (Ref. #6)
  • Rev high affinity binding site is located on Stem Loop 2 of RRE (Ref. #6)
  • 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 (Ref. #7)
  • Rev may exist as a homo-tetramer in solution (Ref. #10)
  • 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

Genomic Location: [TOP]

Reference Sequences:

HIV-1 (HXB2):

          10         20         30         40         50         60         70 
| | | | | | |
MAGRSGDSDE ELIRTVRLIK LLYQSNPPPN PEGTRQARRN RRRRWRERQR QIHSISERIL GTYLGRSAEP
80 90 100 110
| | | |
VPLQLPPLER LTLDCNEDCG TSGTQGVGSP 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 (Ref. #8)
  • An arginine-rich RNA binding-domain mediates interactions with RRE
  • A multimerization domain is required for Rev to function (Ref. #7)
  • Rev has an effector domain, which is a specific Nuclear Export Signal (NES) (Ref. #11 & #12)

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:

Protein-Protein Interactions: [TOP]

  • Serine kinase phosphorylation
  • Serine kinase is present in the nucleus
  • Rev export is mediated through interactions with CRM1, host cell nuclear export factor
  • Rev interacts with RRE RNA - stem loop 2
  • Rev is imported (re-imported) to the nucleus through interactions with Importin-β


Primary and Secondary Database Entries: [TOP]

Identifiers:

ViralZone: HIV-1
PDB/MMDB: Search for HIV-1 & REV

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

PIR: JC4968
HIV: K03455; REV$HXB2
InterPro: IPR000625
Pfam: PF00424
Prints: none
ProDom: PD000783 (residues 1 - 34) / PD387720 (residues 9 - 100) / PD687271 (residues 52 - 101)
PD000769 (residues 57 - 88) / PD604717 (residues 89 - 116)
SCOP: SSF48726 Immunoglobin
BLOCKS: P04618
Prosite: P04618
ProtoNet: P04618
ProtoMap: P04618
PRESAGE: P04618
Database of Interacting Proteins: P04618
ModBase: P04618
Swiss-2DPAGE: 2D gel

BioAfrica Tools:
- Rev Protein Data Mining Tool provides real-time analysis of HIV-1 Rev isolates
- HIV Structure BLAST searches for similar HIV sequences that have known structures
- HIV Proteomics Resource contains protein sequence and structure analysis tools

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]



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