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P04618

- REV_HV1H2

UniProt

P04618 - REV_HV1H2

Protein

Protein Rev

Gene

rev

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    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 By similarity. Interacts with DDX1; the interaction is necessary for proper subcellular localization of this protein.By similarity

    GO - Molecular functioni

    1. protein binding Source: IntAct
    2. RNA binding Source: UniProtKB-KW
    3. sequence-specific DNA binding transcription factor activity Source: InterPro

    GO - Biological processi

    1. entry into host cell Source: Reactome
    2. establishment of integrated proviral latency Source: Reactome
    3. mRNA transport Source: UniProtKB-KW
    4. RNA-dependent DNA replication Source: Reactome
    5. uncoating of virus Source: Reactome
    6. viral life cycle Source: Reactome
    7. viral process Source: Reactome
    8. virion assembly Source: Reactome

    Keywords - Biological processi

    Host-virus interaction, mRNA transport, Transport

    Keywords - Ligandi

    RNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_6190. Rev-mediated nuclear export of HIV RNA.
    REACT_6266. Early Phase of HIV Life Cycle.
    REACT_6359. Budding and maturation of HIV virion.
    REACT_6818. Assembly Of The HIV Virion.
    REACT_6866. Autointegration results in viral DNA circles.
    REACT_6903. Binding and entry of HIV virion.
    REACT_6918. Integration of provirus.
    REACT_6965. Uncoating of the HIV Virion.
    REACT_7991. Vpr-mediated nuclear import of PICs.
    REACT_8990. Integration of viral DNA into host genomic DNA.
    REACT_9037. Plus-strand DNA synthesis.
    REACT_9055. Minus-strand DNA synthesis.
    REACT_9058. 2-LTR circle formation.
    REACT_9395. Nuclear import of Rev protein.
    REACT_9406. APOBEC3G mediated resistance to HIV-1 infection.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein Rev
    Alternative name(s):
    ART/TRS
    Anti-repression transactivator
    Regulator of expression of viral proteins
    Gene namesi
    Name:rev
    OrganismiHuman immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
    Taxonomic identifieri11706 [NCBI]
    Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
    Virus hostiHomo sapiens (Human) [TaxID: 9606]
    ProteomesiUP000002241: Genome

    Subcellular locationi

    Host nucleushost nucleolus. Host cytoplasm
    Note: The presence of both nuclear import and nuclear export signals leads to continuous shuttling between the nucleus and cytoplasm.By similarity

    GO - Cellular componenti

    1. host cell cytoplasm Source: UniProtKB-SubCell
    2. host cell nucleolus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Host cytoplasm, Host nucleus

    Pathology & Biotechi

    Keywords - Diseasei

    AIDS

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 116116Protein RevPRO_0000085279Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei5 – 51Phosphoserine; by host CK21 Publication
    Modified residuei8 – 81Phosphoserine; by host CK21 Publication
    Modified residuei92 – 921Phosphoserine; by hostBy similarity
    Modified residuei99 – 991Phosphoserine; by hostBy similarity

    Post-translational modificationi

    Phosphorylated by protein kinase CK2. Presence of, and maybe binding to the N-terminus of the regulatory beta subunit of CK2 is necessary for CK2-mediated Rev's phosphorylation.3 Publications
    Asymmetrically arginine dimethylated at one site by host PRMT6. Methylation impairs the RNA-binding activity and export of viral RNA from the nucleus to the cytoplasm By similarity.By similarity

    Keywords - PTMi

    Methylation, Phosphoprotein

    Interactioni

    Subunit structurei

    Homomultimer; when bound to the RRE. Multimeric assembly is essential for activity and may involve XPO1. Binds to human KPNB1, XPO1, TNPO1, RANBP5 and IPO7. Interacts with the viral Integrase. Interacts with human KHDRBS1. Interacts with human NAP1; this interaction decreases Rev multimerization and stimulates its activity. Interacts with human DEAD-box helicases DDX3 and DDX24; these interactions may serve for viral RNA export to the cytoplasm and packaging, respectively. Interacts with human PSIP1; this interaction may inhibit HIV-1 DNA integration by promoting dissociation of the Integrase-LEDGF/p75 complex By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CHCHD1Q96BP23EBI-6164309,EBI-5454898From a different organism.
    IKQ131233EBI-6164309,EBI-713456From a different organism.
    MITD1Q8WV922EBI-6164309,EBI-2691489From a different organism.
    MRPS9P829332EBI-6164309,EBI-721385From a different organism.
    SSBP1Q048373EBI-6164309,EBI-353460From a different organism.

    Protein-protein interaction databases

    BioGridi1205542. 226 interactions.
    IntActiP04618. 18 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliP04618.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni18 – 269HomomultimerizationBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi34 – 5017Nuclear localization signal and RNA-binding (RRE)By similarityAdd
    BLAST
    Motifi73 – 8412Nuclear export signal and binding to XPO1By similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi38 – 5013Poly-ArgAdd
    BLAST

    Domaini

    The RNA-binding motif binds to the RRE, a 240 bp stem-and-loop structure present in incompletely spliced viral pre-mRNAs. This region also contains the NLS which mediates nuclear localization via KPNB1 binding and, when the N-terminal sequence is present, nucleolar targeting. These overlapping functions prevent Rev bound to RRE from undesirable return to the nucleus. When Rev binds the RRE, the NLS becomes masked while the NES remains accessible. The leucine-rich NES mediates binding to human XPO1 By similarity.By similarity

    Sequence similaritiesi

    Belongs to the HIV-1 REV protein family.Curated

    Family and domain databases

    InterProiIPR000625. REV_protein.
    [Graphical view]
    PfamiPF00424. REV. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P04618-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAGRSGDSDE ELIRTVRLIK LLYQSNPPPN PEGTRQARRN RRRRWRERQR    50
    QIHSISERIL GTYLGRSAEP VPLQLPPLER LTLDCNEDCG TSGTQGVGSP 100
    QILVESPTVL ESGTKE 116
    Length:116
    Mass (Da):13,075
    Last modified:August 13, 1987 - v1
    Checksum:i4BCF5059C9A7F3B2
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K03455 Genomic RNA. Translation: AAB50257.1.
    PIRiJC4968.
    RefSeqiNP_057854.1. NC_001802.1.

    Genome annotation databases

    GeneIDi155908.

    Cross-referencesi

    Web resourcesi

    BioAfrica HIV proteomics resource

    Rev entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K03455 Genomic RNA. Translation: AAB50257.1 .
    PIRi JC4968.
    RefSeqi NP_057854.1. NC_001802.1.

    3D structure databases

    ProteinModelPortali P04618.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 1205542. 226 interactions.
    IntActi P04618. 18 interactions.

    Chemistry

    BindingDBi P04618.
    ChEMBLi CHEMBL1293282.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 155908.

    Enzyme and pathway databases

    Reactomei REACT_6190. Rev-mediated nuclear export of HIV RNA.
    REACT_6266. Early Phase of HIV Life Cycle.
    REACT_6359. Budding and maturation of HIV virion.
    REACT_6818. Assembly Of The HIV Virion.
    REACT_6866. Autointegration results in viral DNA circles.
    REACT_6903. Binding and entry of HIV virion.
    REACT_6918. Integration of provirus.
    REACT_6965. Uncoating of the HIV Virion.
    REACT_7991. Vpr-mediated nuclear import of PICs.
    REACT_8990. Integration of viral DNA into host genomic DNA.
    REACT_9037. Plus-strand DNA synthesis.
    REACT_9055. Minus-strand DNA synthesis.
    REACT_9058. 2-LTR circle formation.
    REACT_9395. Nuclear import of Rev protein.
    REACT_9406. APOBEC3G mediated resistance to HIV-1 infection.

    Family and domain databases

    InterProi IPR000625. REV_protein.
    [Graphical view ]
    Pfami PF00424. REV. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. "Phosphorylation of HIV-1 Rev protein: implication of protein kinase CK2 and pro-directed kinases."
      Meggio F., D'Agostino D.M., Ciminale V., Chieco-Bianchi L., Pinna L.A.
      Biochem. Biophys. Res. Commun. 226:547-554(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-5 AND SER-8 BY CK2.
    3. "Unique features of HIV-1 Rev protein phosphorylation by protein kinase CK2 ('casein kinase-2')."
      Marin O., Sarno S., Boschetti M., Pagano M.A., Meggio F., Ciminale V., D'Agostino D.M., Pinna L.A.
      FEBS Lett. 481:63-67(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY CK2.
    4. "HIV-1 Rev transactivator: a beta-subunit directed substrate and effector of protein kinase CK2."
      Meggio F., Marin O., Boschetti M., Sarno S., Pinna L.A.
      Mol. Cell. Biochem. 227:145-151(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY CK2.
    5. "A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev."
      Fang J., Kubota S., Yang B., Zhou N., Zhang H., Godbout R., Pomerantz R.J.
      Virology 330:471-480(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DDX1.
    6. Cited for: REVIEW.

    Entry informationi

    Entry nameiREV_HV1H2
    AccessioniPrimary (citable) accession number: P04618
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 13, 1987
    Last sequence update: August 13, 1987
    Last modified: October 1, 2014
    This is version 100 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3