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P69721

- VIF_HV1BR

UniProt

P69721 - VIF_HV1BR

Protein

Virion infectivity factor

Gene

vif

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI) (HIV-1)
Status
Reviewed - Annotation score: 3 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 63 (01 Oct 2014)
      Sequence version 1 (13 Aug 1987)
      Previous versions | rss
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    Functioni

    Counteracts the innate antiviral activity of human APOBEC3F and APOBEC3G. Forms a complex with host APOBEC3F and APOBEC3G thus preventing the entry of these lethally hypermutating enzymes into progeny virions. Recruits an active E3 ubiquitin ligase complex composed of elongin BC, CUL5, and RBX2 to induce polyubiquitination of APOBEC3G and APOBEC3F. In turn, they are directed to the 26S proteasome for degradation. Vif interaction with APOBEC3G also blocks its cytidine deaminase activity in a proteasome-independent manner, suggesting a dual inhibitory mechanism. May interact directly with APOBEC3G mRNA in order to inhibit its translation. Seems to play a role in viral morphology by affecting the stability of the viral nucleoprotein core. Finally, Vif also contributes to the G2 cell cycle arrest observed in HIV infected cells By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei150 – 1512Cleavage in virion (by viral protease)By similarity

    GO - Molecular functioni

    1. RNA binding Source: UniProtKB-KW

    GO - Biological processi

    1. viral life cycle Source: InterPro

    Keywords - Biological processi

    Host-virus interaction, Ubl conjugation pathway

    Keywords - Ligandi

    RNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Virion infectivity factor
    Short name:
    Vif
    Alternative name(s):
    SOR protein
    Cleaved into the following 2 chains:
    Gene namesi
    Name:vif
    OrganismiHuman immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI) (HIV-1)
    Taxonomic identifieri11686 [NCBI]
    Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
    Virus hostiHomo sapiens (Human) [TaxID: 9606]
    ProteomesiUP000007692: Genome

    Subcellular locationi

    Host cytoplasm By similarity. Host cell membrane By similarity; Peripheral membrane protein By similarity; Cytoplasmic side By similarity. Virion By similarity
    Note: In the cytoplasm, seems to colocalize with intermediate filament vimentin. A fraction is associated with the cytoplasmic side of cellular membranes, presumably via the interaction with Pr55Gag precursor. Incorporated in virions at a ratio of approximately 7 to 20 molecules per virion By similarity.By similarity

    GO - Cellular componenti

    1. host cell cytoplasm Source: UniProtKB-SubCell
    2. host cell plasma membrane Source: UniProtKB-SubCell
    3. membrane Source: UniProtKB-KW
    4. virion Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Host cell membrane, Host cytoplasm, Host membrane, Membrane, Virion

    Pathology & Biotechi

    Keywords - Diseasei

    AIDS

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 192192Virion infectivity factorBy similarityPRO_0000043029Add
    BLAST
    Chaini1 – 150150p17By similarityPRO_0000043030Add
    BLAST
    Chaini151 – 19242p7By similarityPRO_0000043031Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei96 – 961Phosphothreonine; by host MAP4K1By similarity
    Modified residuei144 – 1441Phosphoserine; by hostBy similarity
    Modified residuei165 – 1651Phosphoserine; by host MAP4K1By similarity
    Modified residuei188 – 1881Phosphothreonine; by hostBy similarity

    Post-translational modificationi

    Processed in virion by the viral protease.By similarity
    Highly phosphorylated on serines and threonines residues. Thr-96 and Ser-165 are phosphorylated by the mitogen activated kinase MAP4K1. As the HIV-1 replication can be activated by stress and mitogens, these phosphorylations could be involved in this process. Ser-144 phosphorylation may inhibit elongin BC complex binding By similarity.By similarity
    Polyubiquitinated and degraded by the proteasome in the presence of APOBEC3G.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Expressioni

    Inductioni

    Expressed late during infection in a Rev-dependent manner.

    Interactioni

    Subunit structurei

    Homomultimer; in vitro and presumably in vivo. Interacts with viral RNA and Pr55Gag precursor; these interactions mediate Vif incorporation into the virion. Interacts with the viral reverse transcriptase. Interacts with human APOBEC3F and APOBEC3G. Interacts with host UBCE7IP1 isoform 3/ZIN and possibly with SAT. Interacts with host tyrosine kinases HCK and FYN; these interactions may decrease level of phosphorylated APOBEC3G incorporation into virions. Interacts with host ABCE1; this interaction may play a role in protecting viral RNA from damage during viral assembly. Forms an E3 ligase complex by interacting with human CUL5 and elongin BC complex (TCEB1 and TCEB2). Interacts with host MDM2; this interaction targets Vif for degradation by the proteasome By similarity.By similarity

    Protein-protein interaction databases

    BioGridi1205539. 56 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliP69721.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni14 – 174Interaction with host APOBEC3F; F1-boxBy similarity
    Regioni40 – 445Interaction with host APOBEC3G; G-boxBy similarity
    Regioni54 – 7219Interaction with host APOBEC3F and APOBEC3G; FG-boxBy similarityAdd
    BLAST
    Regioni74 – 796Interaction with host APOBEC3F; F2-boxBy similarity
    Regioni75 – 11440RNA-bindingSequence AnalysisAdd
    BLAST
    Regioni151 – 16414MultimerizationBy similarityAdd
    BLAST
    Regioni171 – 1722Membrane associationBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi108 – 13932HCCH motifBy similarityAdd
    BLAST
    Motifi144 – 15310BC-box-like motif

    Domaini

    The BC-like-box motif mediates the interaction with elongin BC complex.By similarity
    The HCCH motif (H-x(5)-C-x(18)-C-x(5)-H) mediates the interaction with CUL5.By similarity

    Sequence similaritiesi

    Family and domain databases

    InterProiIPR000475. Viral_infect.
    [Graphical view]
    PfamiPF00559. Vif. 1 hit.
    [Graphical view]
    PRINTSiPR00349. VIRIONINFFCT.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P69721-1 [UniParc]FASTAAdd to Basket

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    MENRWQVMIV WQVDRMRIRT WKSLVKHHMY VSGKARGWFY RHHYESPHPR    50
    ISSEVHIPLG DARLVITTYW GLHTGERDWH LGQGVSIEWR KKRYSTQVDP 100
    ELADQLIHLY YFDCFSDSAI RKALLGHIVS PRCEYQAGHN KVGSLQYLAL 150
    AALITPKKIK PPLPSVTKLT EDRWNKPQKT KGHRGSHTMN GH 192
    Length:192
    Mass (Da):22,513
    Last modified:August 13, 1987 - v1
    Checksum:iD22589F3955CBE40
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K02013 Genomic RNA. Translation: AAB59748.1.
    A04321 Unassigned RNA. Translation: CAA00351.1.
    RefSeqiNP_057851.1. NC_001802.1.

    Genome annotation databases

    GeneIDi155459.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K02013 Genomic RNA. Translation: AAB59748.1 .
    A04321 Unassigned RNA. Translation: CAA00351.1 .
    RefSeqi NP_057851.1. NC_001802.1.

    3D structure databases

    ProteinModelPortali P69721.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 1205539. 56 interactions.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 155459.

    Family and domain databases

    InterProi IPR000475. Viral_infect.
    [Graphical view ]
    Pfami PF00559. Vif. 1 hit.
    [Graphical view ]
    PRINTSi PR00349. VIRIONINFFCT.
    ProtoNeti Search...

    Publicationsi

    1. "Nucleotide sequence of the AIDS virus, LAV."
      Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M.
      Cell 40:9-17(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. "Identification of a host protein essential for assembly of immature HIV-1 capsids."
      Zimmerman C., Klein K.C., Kiser P.K., Singh A.R., Firestein B.L., Riba S.C., Lingappa J.R.
      Nature 415:88-92(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN ABCE1.
    3. "The viral infectivity factor (Vif) of HIV-1 unveiled."
      Rose K.M., Marin M., Kozak S.L., Kabat D.
      Trends Mol. Med. 10:291-297(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.

    Entry informationi

    Entry nameiVIF_HV1BR
    AccessioniPrimary (citable) accession number: P69721
    Secondary accession number(s): P03401
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: August 13, 1987
    Last modified: October 1, 2014
    This is version 63 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Required for replication in 'nonpermissive' cells, including primary T-cells, macrophages and certain T-cell lines, but is dispensable for replication in 'permissive' cell lines, such as 293T cells. In nonpermissive cells, Vif-defective viruses can produce virions, but they fail to complete reverse transcription and cannot successfully infect new cells.
    Vif-defective viruses show catastrophic failure in reverse transcription due to APOBEC-induced mutations that initiate a DNA base repair pathway and compromise the structural integrity of the ssDNA. In the absence of Vif, the virion is morphologically abnormal.
    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

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3