P69723 (VIF_HV1H2) Reviewed, UniProtKB/Swiss-Prot
Last modified June 11, 2014. Version 68. History...
Names and origin
|Protein names||Recommended name:|
Virion infectivity factor
|Organism||Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1) [Reference proteome]|
|Taxonomic identifier||11706 [NCBI]|
|Taxonomic lineage||Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Lentivirus › Primate lentivirus group ›|
|Virus host||Homo sapiens (Human) [TaxID: 9606]|
|Sequence length||192 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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. Ref.6 Ref.10 Ref.11 Ref.15 Ref.19
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/ZINand 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. Ref.8 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18
Host cytoplasm By similarity. Host cell membrane; Peripheral membrane protein; 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. Ref.2 Ref.4
Expressed late during infection in a Rev-dependent manner.
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.
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. Ref.5 Ref.9
Polyubiquitinated and degraded by the proteasome in the presence of APOBEC3G By similarity.
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).
Belongs to the primate lentivirus group Vif protein family.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 192||192||Virion infectivity factor By similarity||PRO_0000042759|
|Chain||1 – 150||150||p17 By similarity||PRO_0000042760|
|Chain||151 – 192||42||p7 By similarity||PRO_0000042761|
|Region||14 – 17||4||Interaction with host APOBEC3F; F1-box|
|Region||40 – 44||5||Interaction with host APOBEC3G; G-box|
|Region||54 – 72||19||Interaction with host APOBEC3F and APOBEC3G; FG-box|
|Region||74 – 79||6||Interaction with host APOBEC3F; F2-box|
|Region||75 – 114||40||RNA-binding Potential|
|Region||151 – 164||14||Multimerization By similarity|
|Region||171 – 172||2||Membrane association By similarity|
|Motif||108 – 139||32||HCCH motif By similarity|
|Motif||144 – 153||10||BC-box-like motif|
|Site||150 – 151||2||Cleavage in virion (by viral protease) By similarity|
Amino acid modifications
|Modified residue||96||1||Phosphothreonine; by host MAP4K1 Probable|
|Modified residue||144||1||Phosphoserine; by host|
|Modified residue||155||1||Phosphothreonine; by host|
|Modified residue||165||1||Phosphoserine; by host MAP4K1 Probable|
|Modified residue||188||1||Phosphothreonine; by host|
|Mutagenesis||96||1||T → A: 90% loss of reverse transcriptase activity in virions; no effect on the ability to decrease APOBEC3G level. Ref.9|
|Mutagenesis||96||1||T → E: Complete loss of viral infectivity in non permissive cells; no effect on the ability to decrease APOBEC3G level. Ref.9|
|Mutagenesis||114||1||C → S: Reduces the ability to decrease APOBEC3G level; when associated with S-133. Ref.11|
|Mutagenesis||133||1||C → S: Reduces the ability to decrease APOBEC3G level; when associated with S-114. Ref.11|
|Mutagenesis||144||1||S → A: 90% loss of viral infectivity in non permissive cells; no effect on the ability to decrease APOBEC3G level. Ref.5|
|Mutagenesis||157 – 160||4||KKIK → AAIA: 75% loss of membrane binding; decrease Pr55Gag binding. Ref.3|
|Mutagenesis||173 – 179||7||RWNKPQK → AWNAPQA: 40% loss of membrane binding; decrease Pr55Gag binding.|
|Mutagenesis||179 – 184||6||KTKGHR → ATAGHA: 25% loss of membrane binding; decrease Pr55Gag binding.|
|Mutagenesis||188||1||T → A: No effect on the ability to decrease APOBEC3G level. Ref.11|
|||"Complete nucleotide sequences of functional clones of the AIDS virus."|
Ratner L., Fisher A., Jagodzinski L.L., Mitsuya H., Liou R.-S., Gallo R.C., Wong-Staal F.
AIDS Res. Hum. Retroviruses 3:57-69(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"Subcellular localization of the Vif protein of human immunodeficiency virus type 1."|
Goncalves J., Jallepalli P., Gabuzda D.H.
J. Virol. 68:704-712(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
|||"Biological activity of human immunodeficiency virus type 1 Vif requires membrane targeting by C-terminal basic domains."|
Goncalves J., Shi B., Yang X., Gabuzda D.
J. Virol. 69:7196-7204(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF 157-LYS--LYS-160 AND 173-ARG--ARG-184.
|||"Cytoskeleton association and virion incorporation of the human immunodeficiency virus type 1 Vif protein."|
Karczewski M.K., Strebel K.
J. Virol. 70:494-507(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
|||"Phosphorylation of Vif and its role in HIV-1 replication."|
Yang X., Goncalves J., Gabuzda D.
J. Biol. Chem. 271:10121-10129(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, MUTAGENESIS OF SER-144.
|||"Role of Vif in human immunodeficiency virus type 1 reverse transcription."|
Goncalves J., Korin Y., Zack J., Gabuzda D.
J. Virol. 70:8701-8709(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"Characterization of human immunodeficiency virus type 1 Vif particle incorporation."|
Camaur D., Trono D.
J. Virol. 70:6106-6111(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INCORPORATION IN THE VIRION.
|||"Human immunodeficiency virus type 1 Vif protein binds to the Pr55Gag precursor."|
Bouyac M., Courcoul M., Bertoia G., Baudat Y., Gabuzda D., Blanc D., Chazal N., Boulanger P., Sire J., Vigne R., Spire B.
J. Virol. 71:9358-9365(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PR55GAG.
|||"Mitogen-activated protein kinase phosphorylates and regulates the HIV-1 Vif protein."|
Yang X., Gabuzda D.
J. Biol. Chem. 273:29879-29887(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY MAP4K1, PROTEIN SEQUENCE OF 159-164 AND 94-98, MUTAGENESIS OF THR-96.
|||"Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex."|
Yu X., Yu Y., Liu B., Luo K., Kong W., Mao P., Yu X.F.
Science 302:1056-1060(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"Vif overcomes the innate antiviral activity of APOBEC3G by promoting its degradation in the ubiquitin-proteasome pathway."|
Mehle A., Strack B., Ancuta P., Zhang C., McPike M., Gabuzda D.
J. Biol. Chem. 279:7792-7798(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF CYS-114; CYS-133 AND THR-188.
|||"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.
|||"The tyrosine kinases Fyn and Hck favor the recruitment of tyrosine-phosphorylated APOBEC3G into vif-defective HIV-1 particles."|
Douaisi M., Dussart S., Courcoul M., Bessou G., Lerner E.C., Decroly E., Vigne R.
Biochem. Biophys. Res. Commun. 329:917-924(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HOST HCK AND FYN.
|||"Identification of two distinct human immunodeficiency virus type 1 Vif determinants critical for interactions with human APOBEC3G and APOBEC3F."|
Russell R.A., Pathak V.K.
J. Virol. 81:8201-8210(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HOST APOBEC3F AND APOBEC3G.
|||"The Vif accessory protein alters the cell cycle of human immunodeficiency virus type 1 infected cells."|
Wang J., Shackelford J.M., Casella C.R., Shivers D.K., Rapaport E.L., Liu B., Yu X.F., Finkel T.H.
Virology 359:243-252(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL CYCLE ARREST.
|||"Characterization of conserved motifs in HIV-1 Vif required for APOBEC3G and APOBEC3F interaction."|
He Z., Zhang W., Chen G., Xu R., Yu X.F.
J. Mol. Biol. 381:1000-1011(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HOST APOBEC3F AND APOBEC3G.
|||"MDM2 is a novel E3 ligase for HIV-1 Vif."|
Izumi T., Takaori-Kondo A., Shirakawa K., Higashitsuji H., Itoh K., Io K., Matsui M., Iwai K., Kondoh H., Sato T., Tomonaga M., Ikeda S., Akari H., Koyanagi Y., Fujita J., Uchiyama T.
Retrovirology 6:1-1(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HOST MDM2.
|||"Mutational analysis of the HIV-1 auxiliary protein Vif identifies independent domains important for the physical and functional interaction with HIV-1 reverse transcriptase."|
Kataropoulou A., Bovolenta C., Belfiore A., Trabatti S., Garbelli A., Porcellini S., Lupo R., Maga G.
Nucleic Acids Res. 37:3660-3669(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH THE REVERSE TRANSCRIPTASE.
|||"HIV-1 Vif binds to APOBEC3G mRNA and inhibits its translation."|
Mercenne G., Bernacchi S., Richer D., Bec G., Henriet S., Paillart J.C., Marquet R.
Nucleic Acids Res. 38:633-646(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|+||Additional computationally mapped references.|
|BioAfrica HIV proteomics resource |
|K03455 Genomic RNA. Translation: AAB50260.1.|
|RefSeq||NP_057851.1. NC_001802.1. |
3D structure databases
Protein-protein interaction databases
|BioGrid||1205539. 56 interactions.|
Protocols and materials databases
Genome annotation databases
Enzyme and pathway databases
|Reactome||REACT_116125. Disease. |
Family and domain databases
|InterPro||IPR000475. Viral_infect. |
|Pfam||PF00559. Vif. 1 hit. |
|PRINTS||PR00349. VIRIONINFFCT. |
|Accession||Primary (citable) accession number: P69723|
Secondary accession number(s): P03401
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|
Index of protein domains and families