REV_HV1W2
ID REV_HV1W2 Reviewed; 90 AA.
AC P05866;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 23-FEB-2022, entry version 111.
DE RecName: Full=Protein Rev;
DE AltName: Full=ART/TRS;
DE AltName: Full=Anti-repression transactivator;
DE AltName: Full=Regulator of expression of viral proteins;
DE Flags: Fragment;
GN Name=rev;
OS Human immunodeficiency virus type 1 group M subtype B (isolate WMJ22)
OS (HIV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11705;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=3012778; DOI=10.1126/science.3012778;
RA Hahn B.H., Shaw G.M., Taylor M.E., Redfield R.R., Markham P.D.,
RA Salahuddin S.Z., Wong-Staal F., Gallo R.C., Parks E.S., Parks W.P.;
RT "Genetic variation in HTLV-III/LAV over time in patients with AIDS or at
RT risk for AIDS.";
RL Science 232:1548-1553(1986).
RN [2]
RP REVIEW.
RX PubMed=10328811; DOI=10.1006/abbi.1999.1207;
RA Hope T.J.;
RT "The ins and outs of HIV Rev.";
RL Arch. Biochem. Biophys. 365:186-191(1999).
RN [3]
RP STRUCTURE BY NMR OF 8-24 IN COMPLEX WITH RRE-RNA.
RX PubMed=8703216; DOI=10.1126/science.273.5281.1547;
RA Battiste J.L., Mao H., Rao N.S., Tan R., Muhandiram D.R., Kay L.E.,
RA Frankel A.D., Williamson J.R.;
RT "Alpha helix-RNA major groove recognition in an HIV-1 rev peptide-RRE RNA
RT complex.";
RL Science 273:1547-1551(1996).
CC -!- FUNCTION: Escorts unspliced or incompletely spliced viral pre-mRNAs
CC (late transcripts) out of the nucleus of infected cells. These pre-
CC mRNAs carry a recognition sequence called Rev responsive element (RRE)
CC located in the env gene, that is not present in fully spliced viral
CC mRNAs (early transcripts). This function is essential since most viral
CC proteins are translated from unspliced or partially spliced pre-mRNAs
CC which cannot exit the nucleus by the pathway used by fully processed
CC cellular mRNAs. Rev itself is translated from a fully spliced mRNA that
CC readily exits the nucleus. Rev's nuclear localization signal (NLS)
CC binds directly to KPNB1/Importin beta-1 without previous binding to
CC KPNA1/Importin alpha-1. KPNB1 binds to the GDP bound form of RAN (Ran-
CC GDP) and targets Rev to the nucleus. In the nucleus, the conversion
CC from Ran-GDP to Ran-GTP dissociates Rev from KPNB1 and allows Rev's
CC binding to the RRE in viral pre-mRNAs. Rev multimerization on the RRE
CC via cooperative assembly exposes its nuclear export signal (NES) to the
CC surface. Rev can then form a complex with XPO1/CRM1 and Ran-GTP,
CC leading to nuclear export of the complex. Conversion from Ran-GTP to
CC Ran-GDP mediates dissociation of the Rev/RRE/XPO1/RAN complex, so that
CC Rev can return to the nucleus for a subsequent round of export. Beside
CC KPNB1, also seems to interact with TNPO1/Transportin-1, RANBP5/IPO5 and
CC IPO7/RANBP7 for nuclear import. The nucleoporin-like HRB/RIP is an
CC essential cofactor that probably indirectly interacts with Rev to
CC release HIV RNAs from the perinuclear region to the cytoplasm (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homomultimer; when bound to the RRE. Multimeric assembly is
CC essential for activity and may involve XPO1. Binds to human KPNB1,
CC XPO1, TNPO1, RANBP5 and IPO7 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Host nucleus, host nucleolus. Host cytoplasm.
CC Note=The presence of both nuclear import and nuclear export signals
CC leads to continuous shuttling between the nucleus and cytoplasm.
CC {ECO:0000250}.
CC -!- DOMAIN: The RNA-binding motif binds to the RRE, a 240 bp stem-and-loop
CC structure present in incompletely spliced viral pre-mRNAs. This region
CC also contains the NLS which mediates nuclear localization via KPNB1
CC binding and, when the N-terminal sequence is present, nucleolar
CC targeting. These overlapping functions prevent Rev bound to RRE from
CC undesirable return to the nucleus. When Rev binds the RRE, the NLS
CC becomes masked while the NES remains accessible. The leucine-rich NES
CC mediates binding to human XPO1 (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated by protein kinase CK2. Presence of, and maybe
CC binding to the N-terminus of the regulatory beta subunit of CK2 is
CC necessary for CK2-mediated Rev's phosphorylation (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Asymmetrically arginine dimethylated at one site by host PRMT6.
CC Methylation impairs the RNA-binding activity and export of viral RNA
CC from the nucleus to the cytoplasm (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: Isolates WMJ1, WMJ2, and WMJ3 were obtained from blood
CC samples sequentially taken from a two-year old Haitian who was
CC perinatally infected by her mother.
CC -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC majority of strains found worldwide belong to the group M. Group O
CC seems to be endemic to and largely confined to Cameroon and neighboring
CC countries in West Central Africa, where these viruses represent a small
CC minority of HIV-1 strains. The group N is represented by a limited
CC number of isolates from Cameroonian persons. The group M is further
CC subdivided in 9 clades or subtypes (A to D, F to H, J and K).
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DR EMBL; M12507; AAB12992.1; -; Genomic_RNA.
DR PDB; 1ETF; NMR; -; B=8-31.
DR PDB; 1ETG; NMR; -; B=8-31.
DR PDB; 1ULL; NMR; -; B=8-24.
DR PDBsum; 1ETF; -.
DR PDBsum; 1ETG; -.
DR PDBsum; 1ULL; -.
DR SMR; P05866; -.
DR ChEMBL; CHEMBL1293283; -.
DR EvolutionaryTrace; P05866; -.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0044196; C:host cell nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR InterPro; IPR000625; REV_protein.
DR Pfam; PF00424; REV; 1.
PE 1: Evidence at protein level;
KW 3D-structure; AIDS; Host cytoplasm; Host nucleus; Host-virus interaction;
KW Methylation; mRNA transport; Phosphoprotein; RNA-binding; Transport.
FT CHAIN <1..90
FT /note="Protein Rev"
FT /id="PRO_0000085278"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 8..24
FT /note="Nuclear localization signal and RNA-binding (RRE)"
FT /evidence="ECO:0000250"
FT MOTIF 47..58
FT /note="Nuclear export signal and binding to XPO1"
FT /evidence="ECO:0000250"
FT MOD_RES 66
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 73
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250"
FT NON_TER 1
FT HELIX 9..28
FT /evidence="ECO:0007829|PDB:1ETF"
SQ SEQUENCE 90 AA; 10130 MW; DFF0FD284E91E2A1 CRC64;
PPPNPEGTRQ ARRNRRRRWR ERQRQIRSIG AWILSTYLGR SAEPVPLQLP PLERLTLDCE
EDCGTSGTQG VGSPQVLVES PAVLEQGTKE
