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P69723

- VIF_HV1H2

UniProt

P69723 - VIF_HV1H2

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Protein

Virion infectivity factor

Gene
vif
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

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.5 Publications

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. entry into host cell Source: Reactome
  2. establishment of integrated proviral latency Source: Reactome
  3. RNA-dependent DNA replication Source: Reactome
  4. uncoating of virus Source: Reactome
  5. viral life cycle Source: Reactome
  6. viral process Source: Reactome
  7. virion assembly Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Host-virus interaction, Ubl conjugation pathway

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

ReactomeiREACT_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_9406. APOBEC3G mediated resistance to HIV-1 infection.
REACT_9453. Vif-mediated degradation of APOBEC3G.

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 HXB2) (HIV-1)
Taxonomic identifieri11706 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000002241: Genome

Subcellular locationi

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.2 Publications

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
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi96 – 961T → A: 90% loss of reverse transcriptase activity in virions; no effect on the ability to decrease APOBEC3G level. 1 Publication
Mutagenesisi96 – 961T → E: Complete loss of viral infectivity in non permissive cells; no effect on the ability to decrease APOBEC3G level. 1 Publication
Mutagenesisi114 – 1141C → S: Reduces the ability to decrease APOBEC3G level; when associated with S-133. 1 Publication
Mutagenesisi133 – 1331C → S: Reduces the ability to decrease APOBEC3G level; when associated with S-114. 1 Publication
Mutagenesisi144 – 1441S → A: 90% loss of viral infectivity in non permissive cells; no effect on the ability to decrease APOBEC3G level. 1 Publication
Mutagenesisi157 – 1604KKIK → AAIA: 75% loss of membrane binding; decrease Pr55Gag binding. 1 Publication
Mutagenesisi173 – 1797RWNKPQK → AWNAPQA: 40% loss of membrane binding; decrease Pr55Gag binding.
Mutagenesisi179 – 1846KTKGHR → ATAGHA: 25% loss of membrane binding; decrease Pr55Gag binding.
Mutagenesisi188 – 1881T → A: No effect on the ability to decrease APOBEC3G level. 1 Publication

Keywords - Diseasei

AIDS

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 192192Virion infectivity factor By similarityPRO_0000042759Add
BLAST
Chaini1 – 150150p17 By similarityPRO_0000042760Add
BLAST
Chaini151 – 19242p7 By similarityPRO_0000042761Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei96 – 961Phosphothreonine; by host MAP4K1 Inferred
Modified residuei144 – 1441Phosphoserine; by host
Modified residuei155 – 1551Phosphothreonine; by host
Modified residuei165 – 1651Phosphoserine; by host MAP4K1 Inferred
Modified residuei188 – 1881Phosphothreonine; by host

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.2 Publications
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.6 Publications

Protein-protein interaction databases

BioGridi1205539. 56 interactions.

Structurei

3D structure databases

ProteinModelPortaliP69723.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni14 – 174Interaction with host APOBEC3F; F1-box
Regioni40 – 445Interaction with host APOBEC3G; G-box
Regioni54 – 7219Interaction with host APOBEC3F and APOBEC3G; FG-boxAdd
BLAST
Regioni74 – 796Interaction with host APOBEC3F; F2-box
Regioni75 – 11440RNA-binding Reviewed predictionAdd
BLAST
Regioni151 – 16414Multimerization By similarityAdd
BLAST
Regioni171 – 1722Membrane association By similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi108 – 13932HCCH motif By 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.

P69723-1 [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
K03455 Genomic RNA. Translation: AAB50260.1.
RefSeqiNP_057851.1. NC_001802.1.

Genome annotation databases

GeneIDi155459.

Cross-referencesi

Web resourcesi

BioAfrica HIV proteomics resource

Vif entry

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
K03455 Genomic RNA. Translation: AAB50260.1 .
RefSeqi NP_057851.1. NC_001802.1.

3D structure databases

ProteinModelPortali P69723.
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.

Enzyme and pathway databases

Reactomei 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_9406. APOBEC3G mediated resistance to HIV-1 infection.
REACT_9453. Vif-mediated degradation of APOBEC3G.

Family and domain databases

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

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "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.
  3. "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.
  4. "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.
  5. "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.
  6. "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.
  7. "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.
  8. "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.
  9. "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.
  10. "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.
  11. "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.
  12. "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.
  13. "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.
  14. "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.
  15. "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.
  16. "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.
  17. Cited for: INTERACTION WITH HOST MDM2.
  18. "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.
  19. Cited for: FUNCTION.

Entry informationi

Entry nameiVIF_HV1H2
AccessioniPrimary (citable) accession number: P69723
Secondary accession number(s): P03401
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: August 13, 1987
Last modified: September 3, 2014
This is version 69 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, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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