ID REV_HV1H2 Reviewed; 116 AA. AC P04618; DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot. DT 13-AUG-1987, sequence version 1. DT 24-JAN-2024, entry version 144. DE RecName: Full=Protein Rev {ECO:0000255|HAMAP-Rule:MF_04077}; DE AltName: Full=ART/TRS {ECO:0000255|HAMAP-Rule:MF_04077}; DE AltName: Full=Anti-repression transactivator {ECO:0000255|HAMAP-Rule:MF_04077}; DE AltName: Full=Regulator of expression of viral proteins {ECO:0000255|HAMAP-Rule:MF_04077}; GN Name=rev {ECO:0000255|HAMAP-Rule:MF_04077}; OS Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) OS (HIV-1). OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes; OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus; OC Human immunodeficiency virus 1. OX NCBI_TaxID=11706; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=3040055; DOI=10.1089/aid.1987.3.57; RA Ratner L., Fisher A., Jagodzinski L.L., Mitsuya H., Liou R.-S., Gallo R.C., RA Wong-Staal F.; RT "Complete nucleotide sequences of functional clones of the AIDS virus."; RL AIDS Res. Hum. Retroviruses 3:57-69(1987). RN [2] RP PHOSPHORYLATION AT SER-5 AND SER-8 BY CK2. RX PubMed=8806671; DOI=10.1006/bbrc.1996.1392; RA Meggio F., D'Agostino D.M., Ciminale V., Chieco-Bianchi L., Pinna L.A.; RT "Phosphorylation of HIV-1 Rev protein: implication of protein kinase CK2 RT and pro-directed kinases."; RL Biochem. Biophys. Res. Commun. 226:547-554(1996). RN [3] RP PHOSPHORYLATION BY CK2. RX PubMed=10984616; DOI=10.1016/s0014-5793(00)01971-2; RA Marin O., Sarno S., Boschetti M., Pagano M.A., Meggio F., Ciminale V., RA D'Agostino D.M., Pinna L.A.; RT "Unique features of HIV-1 Rev protein phosphorylation by protein kinase CK2 RT ('casein kinase-2')."; RL FEBS Lett. 481:63-67(2000). RN [4] RP PHOSPHORYLATION BY CK2. RX PubMed=11827166; DOI=10.1023/a:1013177326481; RA Meggio F., Marin O., Boschetti M., Sarno S., Pinna L.A.; RT "HIV-1 Rev transactivator: a beta-subunit directed substrate and effector RT of protein kinase CK2."; RL Mol. Cell. Biochem. 227:145-151(2001). RN [5] RP INTERACTION WITH DDX1. RX PubMed=15567440; DOI=10.1016/j.virol.2004.09.039; RA Fang J., Kubota S., Yang B., Zhou N., Zhang H., Godbout R., Pomerantz R.J.; RT "A DEAD box protein facilitates HIV-1 replication as a cellular co-factor RT of Rev."; RL Virology 330:471-480(2004). RN [6] 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). 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 {ECO:0000255|HAMAP-Rule:MF_04077}. 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. {ECO:0000255|HAMAP-Rule:MF_04077}. CC -!- INTERACTION: CC P04618; P04618: rev; NbExp=3; IntAct=EBI-6164309, EBI-6164309; CC P04618; Q96BP2: CHCHD1; Xeno; NbExp=3; IntAct=EBI-6164309, EBI-5454898; CC P04618; Q92499-1: DDX1; Xeno; NbExp=6; IntAct=EBI-6164309, EBI-15532186; CC P04618; P17844: DDX5; Xeno; NbExp=2; IntAct=EBI-6164309, EBI-351962; CC P04618; Q13123: IK; Xeno; NbExp=3; IntAct=EBI-6164309, EBI-713456; CC P04618; Q8WV92: MITD1; Xeno; NbExp=2; IntAct=EBI-6164309, EBI-2691489; CC P04618; P82933: MRPS9; Xeno; NbExp=2; IntAct=EBI-6164309, EBI-721385; CC P04618; Q92621: NUP205; Xeno; NbExp=2; IntAct=EBI-6164309, EBI-1045046; CC P04618; Q04837: SSBP1; Xeno; NbExp=3; IntAct=EBI-6164309, EBI-353460; CC P04618; O14980: XPO1; Xeno; NbExp=2; IntAct=EBI-6164309, EBI-355867; CC -!- SUBCELLULAR LOCATION: Host nucleus, host nucleolus {ECO:0000255|HAMAP- CC Rule:MF_04077}. Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04077}. CC Note=The presence of both nuclear import and nuclear export signals CC leads to continuous shuttling between the nucleus and cytoplasm. CC {ECO:0000255|HAMAP-Rule:MF_04077}. 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. {ECO:0000255|HAMAP-Rule:MF_04077}. 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. {ECO:0000255|HAMAP-Rule:MF_04077}. 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. {ECO:0000255|HAMAP- CC Rule:MF_04077, ECO:0000269|PubMed:10984616, CC ECO:0000269|PubMed:11827166, ECO:0000269|PubMed:8806671}. 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 {ECO:0000255|HAMAP-Rule:MF_04077}. CC -!- SIMILARITY: Belongs to the HIV-1 REV protein family. CC {ECO:0000255|HAMAP-Rule:MF_04077}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; K03455; AAB50257.1; -; Genomic_RNA. DR PIR; JC4968; JC4968. DR RefSeq; NP_057854.1; NC_001802.1. DR PDB; 6HIP; X-ray; 1.20 A; C=41-49. DR PDB; 7JYA; X-ray; 2.46 A; D/E/F=40-50. DR PDBsum; 6HIP; -. DR PDBsum; 7JYA; -. DR EMDB; EMD-6231; -. DR SMR; P04618; -. DR BioGRID; 1205542; 228. DR DIP; DIP-61717N; -. DR IntAct; P04618; 25. DR BindingDB; P04618; -. DR ChEMBL; CHEMBL1293282; -. DR iPTMnet; P04618; -. DR ABCD; P04618; 1 sequenced antibody. DR GeneID; 155908; -. DR KEGG; vg:155908; -. DR Reactome; R-HSA-162585; Uncoating of the HIV Virion. DR Reactome; R-HSA-162588; Budding and maturation of HIV virion. DR Reactome; R-HSA-162592; Integration of provirus. DR Reactome; R-HSA-162594; Early Phase of HIV Life Cycle. DR Reactome; R-HSA-164516; Minus-strand DNA synthesis. DR Reactome; R-HSA-164525; Plus-strand DNA synthesis. DR Reactome; R-HSA-164843; 2-LTR circle formation. DR Reactome; R-HSA-165054; Rev-mediated nuclear export of HIV RNA. DR Reactome; R-HSA-173107; Binding and entry of HIV virion. DR Reactome; R-HSA-175474; Assembly Of The HIV Virion. DR Reactome; R-HSA-175567; Integration of viral DNA into host genomic DNA. DR Reactome; R-HSA-177539; Autointegration results in viral DNA circles. DR Reactome; R-HSA-180689; APOBEC3G mediated resistance to HIV-1 infection. DR Reactome; R-HSA-180746; Nuclear import of Rev protein. DR Reactome; R-HSA-180910; Vpr-mediated nuclear import of PICs. DR PRO; PR:P04618; -. DR Proteomes; UP000002241; Segment. 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:UniProtKB-UniRule. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-UniRule. DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-UniRule. DR GO; GO:0016032; P:viral process; IEA:UniProtKB-UniRule. DR Gene3D; 6.10.140.630; -; 1. DR HAMAP; MF_04077; REV_HIV1; 1. 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; Reference proteome; KW RNA-binding; Transport. FT CHAIN 1..116 FT /note="Protein Rev" FT /id="PRO_0000085279" FT REGION 18..26 FT /note="Homomultimerization" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04077" FT REGION 21..49 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 92..116 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 34..50 FT /note="Nuclear localization signal and RNA-binding (RRE)" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04077" FT MOTIF 73..84 FT /note="Nuclear export signal and binding to XPO1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04077" FT MOD_RES 5 FT /note="Phosphoserine; by host CK2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04077, FT ECO:0000269|PubMed:8806671" FT MOD_RES 8 FT /note="Phosphoserine; by host CK2" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04077, FT ECO:0000269|PubMed:8806671" FT MOD_RES 92 FT /note="Phosphoserine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04077" FT MOD_RES 99 FT /note="Phosphoserine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04077" FT TURN 45..48 FT /evidence="ECO:0007829|PDB:7JYA" SQ SEQUENCE 116 AA; 13075 MW; 4BCF5059C9A7F3B2 CRC64; MAGRSGDSDE ELIRTVRLIK LLYQSNPPPN PEGTRQARRN RRRRWRERQR QIHSISERIL GTYLGRSAEP VPLQLPPLER LTLDCNEDCG TSGTQGVGSP QILVESPTVL ESGTKE //