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

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.

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)

• 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

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

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]