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P69723 (VIF_HV1H2) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 68. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Virion infectivity factor

Short name=Vif
Alternative name(s):
SOR protein

Cleaved into the following 2 chains:

  1. p17
  2. p7
Gene names
Name:vif
OrganismHuman immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1) [Reference proteome]
Taxonomic identifier11706 [NCBI]
Taxonomic lineageVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length192 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Subunit structure

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

Subcellular location

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

Induction

Expressed late during infection in a Rev-dependent manner.

Domain

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.

Post-translational modification

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.

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).

Sequence similarities

Belongs to the primate lentivirus group Vif protein family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 192192Virion infectivity factor By similarity
PRO_0000042759
Chain1 – 150150p17 By similarity
PRO_0000042760
Chain151 – 19242p7 By similarity
PRO_0000042761

Regions

Region14 – 174Interaction with host APOBEC3F; F1-box
Region40 – 445Interaction with host APOBEC3G; G-box
Region54 – 7219Interaction with host APOBEC3F and APOBEC3G; FG-box
Region74 – 796Interaction with host APOBEC3F; F2-box
Region75 – 11440RNA-binding Potential
Region151 – 16414Multimerization By similarity
Region171 – 1722Membrane association By similarity
Motif108 – 13932HCCH motif By similarity
Motif144 – 15310BC-box-like motif

Sites

Site150 – 1512Cleavage in virion (by viral protease) By similarity

Amino acid modifications

Modified residue961Phosphothreonine; by host MAP4K1 Probable
Modified residue1441Phosphoserine; by host
Modified residue1551Phosphothreonine; by host
Modified residue1651Phosphoserine; by host MAP4K1 Probable
Modified residue1881Phosphothreonine; by host

Experimental info

Mutagenesis961T → A: 90% loss of reverse transcriptase activity in virions; no effect on the ability to decrease APOBEC3G level. Ref.9
Mutagenesis961T → E: Complete loss of viral infectivity in non permissive cells; no effect on the ability to decrease APOBEC3G level. Ref.9
Mutagenesis1141C → S: Reduces the ability to decrease APOBEC3G level; when associated with S-133. Ref.11
Mutagenesis1331C → S: Reduces the ability to decrease APOBEC3G level; when associated with S-114. Ref.11
Mutagenesis1441S → A: 90% loss of viral infectivity in non permissive cells; no effect on the ability to decrease APOBEC3G level. Ref.5
Mutagenesis157 – 1604KKIK → AAIA: 75% loss of membrane binding; decrease Pr55Gag binding. Ref.3
Mutagenesis173 – 1797RWNKPQK → AWNAPQA: 40% loss of membrane binding; decrease Pr55Gag binding.
Mutagenesis179 – 1846KTKGHR → ATAGHA: 25% loss of membrane binding; decrease Pr55Gag binding.
Mutagenesis1881T → A: No effect on the ability to decrease APOBEC3G level. Ref.11

Sequences

Sequence LengthMass (Da)Tools
P69723 [UniParc].

Last modified August 13, 1987. Version 1.
Checksum: D22589F3955CBE40

FASTA19222,513
        10         20         30         40         50         60 
MENRWQVMIV WQVDRMRIRT WKSLVKHHMY VSGKARGWFY RHHYESPHPR ISSEVHIPLG 

        70         80         90        100        110        120 
DARLVITTYW GLHTGERDWH LGQGVSIEWR KKRYSTQVDP ELADQLIHLY YFDCFSDSAI 

       130        140        150        160        170        180 
RKALLGHIVS PRCEYQAGHN KVGSLQYLAL AALITPKKIK PPLPSVTKLT EDRWNKPQKT 

       190 
KGHRGSHTMN GH 

« Hide

References

[1]"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].
[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]"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.
[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]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
K03455 Genomic RNA. Translation: AAB50260.1.
RefSeqNP_057851.1. NC_001802.1.

3D structure databases

ProteinModelPortalP69723.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid1205539. 56 interactions.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID155459.

Enzyme and pathway databases

ReactomeREACT_116125. Disease.

Family and domain databases

InterProIPR000475. Viral_infect.
[Graphical view]
PfamPF00559. Vif. 1 hit.
[Graphical view]
PRINTSPR00349. VIRIONINFFCT.
ProtoNetSearch...

Entry information

Entry nameVIF_HV1H2
AccessionPrimary (citable) accession number: P69723
Secondary accession number(s): P03401
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: August 13, 1987
Last modified: June 11, 2014
This is version 68 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families