DP00424: Protein RevFASTA viewXML view

General information
Name:Protein Rev
Regulator of expression of viral proteins
Anti-repression transactivator
First appeared in release:Release 3.0 (02/17/2006)
SwissProt: REV_HV112
NCBI (GI): 132414
Source organism:Human immunodeficiency virus type 1 (HIV-1)
Sequence length:116
Percent disordered:47%

Native sequence

        10         20         30         40         50         60
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Functional narrative    

The Rev protein of human immunodeficiency virus type 1 (HIV-1) is a 116-amino-acid phosphoprotein that is essential for expression of the incompletely spliced mRNAs encoding the structural viral proteins. Direct interaction of Rev with a stem-loop structure termed the Rev-responsive element (RRE) located in this subset of mRNAs protects them from splicing and degradation, facilitates their nuclear-cytoplasmic transport, and promotes their utilization in the cytoplasm. Although Rev is detected primarily in the nuclei and nucleoli of human cells under steady-state conditions, it is known to shuttle between the nucleus and the cytoplasm, thereby supporting the efficient expression of the late viral enzymatic and structural proteins encoded by these mRNAs. In addition to accumulating in nucleoli, Rev has been demonstrated to partially colocalize with the splicing factor SC35 in nuclear speckles or in the vicinity of nuclear speckles. Escorts unspliced or incompletely spliced viral pre-mRNAs (late transcripts) out of the nucleus of infected cells. These pre-mRNAs carry a recognition sequence called Rev responsive element (RRE) located in the env gene, that is not present in fully spliced viral mRNAs (early transcripts). This function is essential since most viral proteins are translated from unspliced or partially spliced pre-mRNAs which cannot exit the nucleus by the pathway used by fully processed cellular mRNAs. Rev itself is translated from a fully spliced mRNA that readily exits the nucleus. Rev's nuclear localization signal (NLS) binds directly to KPNB1/Importin beta-1 without previous binding to KPNA1/Importin alpha-1. KPNB1 binds to the GDP bound form of RAN (Ran-GDP) and targets Rev to the nucleus. In the nucleus, the conversion from Ran-GDP to Ran-GTP dissociates Rev from KPNB1 and allows Rev's binding to the RRE in viral pre-mRNAs. Rev multimerization on the RRE via cooperative assembly exposes its nuclear export signal (NES) to the surface. Rev can then form a complex with XPO1/CRM1 and Ran-GTP, leading to nuclear export of the complex. Conversion from Ran-GTP to Ran-GDP mediates dissociation of the Rev/RRE/XPO1/RAN complex, so that Rev can return to the nucleus for a subsequent round of export. Beside KPNB1, also seems to interact with TNPO1/Transportin-1, RANBP5/IPO5 and IPO7/RANBP7 for nuclear import. The nucleoporin-like HRB/RIP is an essential cofactor that probably indirectly interacts with Rev to release HIV RNAs from the perinuclear region to the cytoplasm.

Region 1: 62-116

Map of ordered and disordered regions

Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.

Region 1
Name:C-terminal region
Location:62 - 116
Region sequence:


Modification type: Fragment
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular assembly
Functional subclasses: Nuclear localization
Transactivation (transcriptional activation)
Protein-protein binding
Detection methods:
  1. Circular dichroism (CD) spectroscopy, far-UV (283 K; pH: 6.5; MES 20 mM)

  2. Circular dichroism (CD) spectroscopy, far-UV (278 K; pH: 3; potassium phosphate 20 mM)

  1. Auer M, Gremlich HU, Seifert JM, Daly TJ, Parslow TG, Casari G, Gstach H. "Helix-loop-helix motif in HIV-1 Rev." Biochemistry. 1994; 33(10): 2988-96. PubMed: 7510518

  2. Daly TJ, Rusche JR, Maione TE, Frankel AD. "Circular dichroism studies of the HIV-1 Rev protein and its specific RNA binding site." Biochemistry. 1990; 29(42): 9791-5. PubMed: 2125482



  1. Hakata Y, Yamada M, Mabuchi N, Shida H. "The carboxy-terminal region of the human immunodeficiency virus type 1 protein Rev has multiple roles in mediating CRM1-related Rev functions." J Virol. 2002; 76(16): 8079-89. PubMed: 12134013

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