REV - ART/TRS Anti-repression transactivator protein
HIV REV
upregulates expression of Gag, Pol and Env, while downregulating itself and Tat.
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[animated gif: 320x240 ]
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Isoforms:
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Localization:
- nucleolus/nucleus
- cytoplasm [shuttling between nucleolus and cytoplasm]
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Function:
- regulatory protein
- 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)
- binds to RRE, which facilitates export of unspliced and incompletely spliced viral RNA from nucleus to cytoplasm
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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
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Genomic Location: [TOP]
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Reference
Sequences: HIV-1
(HXB2):
10 20 30 40 50 60 70
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MAGRSGDSDE ELIRTVRLIK LLYQSNPPPN PEGTRQARRN RRRRWRERQR QIHSISERIL GTYLGRSAEP
80 90 100 110
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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.
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Protein Domains/Folds/Motifs: [TOP]
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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)
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Secondary Structure prediction:
Low Complexity Regions - seg:
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N-glycosylation:
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N-myristoylation:
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Amidation:
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Protein kinase C:
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Casein kinase II:
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Tyrosine kinase:
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cAMP / cGMP kinase:
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Cell attachment motif:
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Asp Protease motif:
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Asp Prot Retro motif:
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Arginine-rich Region:
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Cysteine-rich Region:
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Tryptophan-rich Region:
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Zinc-finger CCHC motif:
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Leucine Zipper motif:
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Protein-Protein Interactions: [TOP]
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- 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
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Primary and Secondary Database Entries: [TOP]
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Identifiers:
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
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Reviews and References: [TOP]
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- 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]
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