AC   MF_04077;
DC   Protein; auto
TR   HAMAP; MF_04077; -; 1; level=0
XX
Names: REV_HIV1
XX
ID   REV
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;
GN   Name=rev;
XX
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.
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. Interacts with the viral Integrase.
CC       Interacts with human KHDRBS1. Interacts with human NAP1; this
CC       interaction decreases Rev multimerization and stimulates its activity.
CC       Interacts with human DEAD-box helicases DDX3 and DDX24; these
CC       interactions may serve for viral RNA export to the cytoplasm and
CC       packaging, respectively. Interacts with human PSIP1; this interaction
CC       may inhibit HIV-1 DNA integration by promoting dissociation of the
CC       Integrase-LEDGF/p75 complex.
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   -!- 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.
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.
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.
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).
CC   -!- SIMILARITY: Belongs to the HIV-1 REV protein family.
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DR   Pfam; PF00424; REV; 1; trigger=no
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KW   Host cytoplasm
KW   Host nucleus
KW   Host-virus interaction
KW   Methylation
KW   mRNA transport
KW   Phosphoprotein
KW   RNA-binding
KW   Transport
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GO   GO:0030430; C:host cell cytoplasm
GO   GO:0044196; C:host cell nucleolus
GO   GO:0003723; F:RNA binding
GO   GO:0003700; F:DNA-binding transcription factor activity
GO   GO:0051028; P:mRNA transport
GO   GO:0016032; P:viral process
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FT   From: REV_HV1H2 (P04618)
FT   REGION          18..26
FT                   /note="Homomultimerization"
FT   MOTIF           34..50
FT                   /note="Nuclear localization signal and RNA-binding (RRE)"
FT   MOTIF           73..84
FT                   /note="Nuclear export signal and binding to XPO1"
FT   MOD_RES         5
FT                   /note="Phosphoserine; by host CK2"
FT   Condition: S
FT   MOD_RES         8
FT                   /note="Phosphoserine; by host CK2"
FT   Condition: S
FT   MOD_RES         92
FT                   /note="Phosphoserine; by host"
FT   Condition: S
FT   MOD_RES         99
FT                   /note="Phosphoserine; by host"
FT   Condition: S
XX
Size: 102-123;
Related: None;
Template: P04618;
Scope:
 Viruses; Lentivirus
Fusion:
 Nter: None
 Cter: None
Duplicate: None
Plasmid: None
Comments: None
XX
# Revision 1.7 2019/11/20
//