P12504 (VIF_HV1N5) Reviewed, UniProtKB/Swiss-Prot
Last modified May 1, 2013. Version 86. History...
Names and origin
|Protein names||Recommended name:|
Virion infectivity factor
|Organism||Human immunodeficiency virus type 1 group M subtype B (isolate NY5) (HIV-1)|
|Taxonomic identifier||11698 [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 By similarity. Ref.4 Ref.10
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. Ref.6 Ref.7 Ref.8 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16
Host cytoplasm. Host cell membrane; Peripheral membrane protein; Cytoplasmic side. Virion. Note: 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.
Expressed late during infection in a Rev-dependent manner. Ref.3
The BC-like-box motif mediates the interaction with elongin BC complex.
The HCCH motif (H-x(5)-C-x(18)-C-x(5)-H) mediates the interaction with CUL5.
Processed in virion by the viral protease.
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.
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.
The infectious clone pNL4-3 is a chimeric provirus that consists of DNA from HIV isolates NY5 (5' half) and BRU (3' half).
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.
|AMBRA1||Q9C0C7||5||EBI-779991,EBI-2512975||From a different organism.|
|CBFB||Q13951||5||EBI-779991,EBI-718750||From a different organism.|
|CUL2||Q13617||5||EBI-779991,EBI-456179||From a different organism.|
|CUL5||Q93034||5||EBI-779991,EBI-1057139||From a different organism.|
|DCAF11||Q8TEB1||3||EBI-779991,EBI-2213388||From a different organism.|
|DNAJC7||Q99615||3||EBI-779991,EBI-357552||From a different organism.|
|GPS2||Q13227||2||EBI-779991,EBI-713355||From a different organism.|
|HCK||P08631||3||EBI-779991,EBI-346340||From a different organism.|
|HDAC3||O15379||2||EBI-779991,EBI-607682||From a different organism.|
|MAPK6||Q16659||2||EBI-779991,EBI-1384105||From a different organism.|
|PSME3||P61289||2||EBI-779991,EBI-355546||From a different organism.|
|RNF216||Q9NWF9-3||4||EBI-779991,EBI-723337||From a different organism.|
|RNF7||Q9UBF6||4||EBI-779991,EBI-398632||From a different organism.|
|SQSTM1||Q13501||2||EBI-779991,EBI-307104||From a different organism.|
|STUB1||Q9UNE7||2||EBI-779991,EBI-357085||From a different organism.|
|TCEB1||Q15369||5||EBI-779991,EBI-301231||From a different organism.|
|TCEB2||Q15370||5||EBI-779991,EBI-301238||From a different organism.|
|UBL4A||P11441||2||EBI-779991,EBI-356983||From a different organism.|
|UBR2||Q8IWV8||3||EBI-779991,EBI-1237260||From a different organism.|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 192||192||Virion infectivity factor||PRO_0000042762|
|Chain||1 – 150||150||Virion infectivity factor p17||PRO_0000042763|
|Chain||151 – 192||42||Virion infectivity factor p7||PRO_0000042764|
|Region||14 – 17||4||Interaction with host APOBEC3F; F1-box By similarity|
|Region||40 – 44||5||Interaction with host APOBEC3G; G-box By similarity|
|Region||54 – 72||19||Interaction with host APOBEC3F and APOBEC3G; FG-box By similarity|
|Region||74 – 79||6||Interaction with host APOBEC3F; F2-box By similarity|
|Region||75 – 114||40||RNA-binding Potential|
|Region||151 – 164||14||Multimerization|
|Region||171 – 172||2||Membrane association|
|Motif||108 – 139||32||HCCH motif|
|Motif||144 – 153||10||BC-box-like motif|
|Site||150 – 151||2||Cleavage in virion (by viral protease)|
Amino acid modifications
|Modified residue||96||1||Phosphothreonine; by host MAP4K1 By similarity|
|Modified residue||144||1||Phosphoserine; by host By similarity|
|Modified residue||165||1||Phosphoserine; by host MAP4K1 By similarity|
|Modified residue||188||1||Phosphothreonine; by host By similarity|
|Natural variant||90 – 93||4||RKKR → KKRK in strain: Clinical isolate; from an asymptomatic patient; Vif is mislocalized to the nucleus and non functional. |
|Mutagenesis||5 – 6||2||WQ → AA: 44% loss of viral infectivity.|
|Mutagenesis||12 – 13||2||QV → AA: No effect on viral infectivity.|
|Mutagenesis||16 – 18||3||MRI → AAA: 29% loss of viral infectivity. Ref.5|
|Mutagenesis||23 – 24||2||RL → AA: 14% loss of viral infectivity.|
|Mutagenesis||29 – 31||3||MYI → AAV: 59% loss of viral infectivity. Ref.5|
|Mutagenesis||33 – 34||2||RK → AA: 35% loss of viral infectivity.|
|Mutagenesis||38 – 40||3||WFY → AAA: 94% loss of viral infectivity. Ref.5|
|Mutagenesis||43 – 44||2||HY → AA: 95% loss of viral infectivity.|
|Mutagenesis||53 – 54||2||SE → AA: 39% loss of viral infectivity.|
|Mutagenesis||58 – 59||2||PL → AA: 45% loss of viral infectivity.|
|Mutagenesis||69 – 70||2||YW → AA: 97% loss of viral infectivity.|
|Mutagenesis||73 – 74||2||HT → AA: No effect onviral infectivity.|
|Mutagenesis||80 – 81||2||HL → AA: 19% loss of viral infectivity.|
|Mutagenesis||86 – 87||2||SI → AA: 42% loss of viral infectivity.|
|Mutagenesis||90 – 92||3||RKK → AAA: No effect on viral infectivity. Ref.5|
|Mutagenesis||97 – 98||2||QV → AA: 27% loss of viral infectivity.|
|Mutagenesis||105 – 107||3||QLI → AAV: 98% loss of viral infectivity. Ref.5|
|Mutagenesis||108||1||H → L: Complete loss of interaction with CUL5. Ref.16|
|Mutagenesis||111 – 112||2||YF → AA: 93% loss of viral infectivity.|
|Mutagenesis||114||1||C → S: 98% loss of viral infectivity. Complete loss of interaction with CUL5. Ref.5 Ref.14 Ref.16|
|Mutagenesis||121 – 123||3||RNT → AAA: 35% increase of viral infectivity. Ref.5|
|Mutagenesis||127 – 128||2||RI → AA: 10% loss of viral infectivity.|
|Mutagenesis||133||1||C → S: 95% loss of viral infectivity. Complete loss of interaction with CUL5. Ref.5 Ref.14 Ref.16|
|Mutagenesis||135 – 136||2||YQ → AA: 73% loss of viral infectivity.|
|Mutagenesis||139||1||H → L: Complete loss of interaction with CUL5. Ref.16|
|Mutagenesis||140 – 141||2||NK → AA: 68% loss of viral infectivity.|
|Mutagenesis||144 – 146||3||SLQ → AAA: 93% loss of viral infectivity. Ref.5 Ref.13|
|Mutagenesis||144||1||S → A: 25% loss of interaction with CUL5y. Ref.13|
|Mutagenesis||145||1||L → A: Complete loss of interaction with CUL5. Ref.13|
|Mutagenesis||146||1||Q → A: 90% loss of interaction with CUL5. Ref.13|
|Mutagenesis||147 – 148||2||YL → AA: 40% loss of viral infectivity. Ref.13|
|Mutagenesis||147||1||Y → A: 40% loss of interaction with CUL5. Ref.13|
|Mutagenesis||148||1||L → A: 35% loss of interaction with CUL5. Ref.13|
|Mutagenesis||149 – 151||3||ALA → RKS: Complete loss of processing between p17 and p7. Complete loss of replication. Ref.9 Ref.13|
|Mutagenesis||149||1||A → G: 75% loss of CUL5 binding activity. Ref.13|
|Mutagenesis||150||1||L → A: 90% loss of CUL5 binding activity. Ref.13|
|Mutagenesis||151||1||A → E: No effect on processing between p17 and p7.|
|Mutagenesis||151||1||A → N: Slightly increased processing between p17 and p7.|
|Mutagenesis||151||1||A → P: Increased processing between p17 and p7.|
|Mutagenesis||151||1||A → Y: Partial loss of processing between p17 and p7.|
|Mutagenesis||156 – 158||3||PKQ → AAA: No effect on viral infectivity. Ref.5|
|Mutagenesis||157||1||K → A: No effect viral infectivity. Ref.5|
|Mutagenesis||158 – 160||3||QIK → AAA: 9% loss of viral infectivity. Ref.5|
|Mutagenesis||160||1||K → A: 33% loss of viral infectivity.|
|Mutagenesis||161 – 164||4||PPLP → APLA: 88% loss of viral infectivity. Ref.5|
|Mutagenesis||161 – 163||3||PPL → AAA: 97% loss of viral infectivity.|
|Mutagenesis||161||1||P → A: 27% loss of viral infectivity.|
|Mutagenesis||162||1||P → A: No effect viral infectivity.|
|Mutagenesis||163||1||L → A: 26% loss of viral infectivity.|
|Mutagenesis||164||1||P → A: 63% loss of viral infectivity.|
|Mutagenesis||165||1||S → A: 67% loss of viral infectivity. Ref.5|
|Mutagenesis||166||1||V → A: 20% loss of viral infectivity. Ref.5|
|Mutagenesis||169 – 170||2||LT → AA: 42% loss of viral infectivity.|
|Mutagenesis||180 – 181||2||TK → AA: 5% loss of viral infectivity.|
|Mutagenesis||189 – 190||2||MN → AA: 4% loss of viral infectivity.|
Helix Strand Turn
|Helix||145 – 154||10|
|||Buckler C.E., Buckler-White A.J., Willey R.L., McCoy J.|
Submitted (JUN-1988) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Strain: Clone pNL4-3.
|||Theodore T., Buckler-White A.J.|
Submitted (OCT-1992) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"Expression of human immunodeficiency virus type 1 vif and vpr mRNAs is Rev-dependent and regulated by splicing."|
Schwartz S., Felber B.K., Pavlakis G.N.
Virology 183:677-686(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
|||"Role of vif during packing of the core of HIV-1."|
Hoglund S., Ohagen A., Lawrence K., Gabuzda D.
Virology 201:349-355(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: ROLE IN VIRION MORPHOLOGY.
|||"Mutational analysis of the human immunodeficiency virus type 1 Vif protein."|
Simon J.H., Sheehy A.M., Carpenter E.A., Fouchier R.A., Malim M.H.
J. Virol. 73:2675-2681(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF 5-TRP-GLN-6; 12-GLN-VAL-13; 16-MET--ILE-18; 23-ARG-LEU-24; 29-MET--ILE-31; 33-ARG-LYS-34; 38-TRP--TYR-40; 43-HIS-TYR-44; 53-SER-GLU-54; 58-PRO-LEU-59; 69-TYR-TRP-70; 73-HIS-THR-74; 80-HIS-LEU-81; 86-SER-ILE-87; 90-ARG--LYS-92; 97-GLN-VAL-98; 105-GLN--ILE-107; 111-TYR-PHE-112; CYS-114; 121-ARG--THR-123; 127-ARG-ILE-128; CYS-133; 135-TYR-GLN-136; 140-ASN-LYS-141; 144-SER--GLN-146; 147-TYR-LEU-148; 156-PRO--GLN-158; LYS-157; 158-GLN--LYS-160; 161-PRO--LEU-164; SER-165; VAL-166; 169-LEU-THR-170; 180-THR-LYS-181 AND 189-MET-ASN-190.
|||"The multimerization of human immunodeficiency virus type I Vif protein: a requirement for Vif function in the viral life cycle."|
Yang S., Sun Y., Zhang H.
J. Biol. Chem. 276:4889-4893(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: MULTIMERIZATION.
|||"Human immunodeficiency virus type 1 Vif protein is packaged into the nucleoprotein complex through an interaction with viral genomic RNA."|
Khan M.A., Aberham C., Kao S., Akari H., Gorelick R., Bour S., Strebel K.
J. Virol. 75:7252-7265(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NUCLEOPROTEIN.
|||"The tyrosine kinase Hck is an inhibitor of HIV-1 replication counteracted by the viral vif protein."|
Hassaine G., Courcoul M., Bessou G., Barthalay Y., Picard C., Olive D., Collette Y., Vigne R., Decroly E.
J. Biol. Chem. 276:16885-16893(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN HCK.
|||"Intravirion processing of the human immunodeficiency virus type 1 Vif protein by the viral protease may be correlated with Vif function."|
Khan M.A., Akari H., Kao S., Aberham C., Davis D., Buckler-White A., Strebel K.
J. Virol. 76:9112-9123(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-9 AND 151-162, CLEAVAGE BY VIRAL PROTEASE, MUTAGENESIS OF 149-ALA--ALA-151.
|||"The human immunodeficiency virus type 1 Vif protein reduces intracellular expression and inhibits packaging of APOBEC3G (CEM15), a cellular inhibitor of virus infectivity."|
Kao S., Khan M.A., Miyagi E., Plishka R., Buckler-White A., Strebel K.
J. Virol. 77:11398-11407(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"The role of Vif during HIV-1 infection: interaction with novel host cellular factors."|
Lake J.A., Carr J., Feng F., Mundy L., Burrell C., Li P.
J. Clin. Virol. 26:143-152(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN SAT.
|||"HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation."|
Marin M., Rose K.M., Kozak S.L., Kabat D.
Nat. Med. 9:1398-1403(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN APOBEC3G.
|||"Phosphorylation of a novel SOCS-box regulates assembly of the HIV-1 Vif-Cul5 complex that promotes APOBEC3G degradation."|
Mehle A., Goncalves J., Santa-Marta M., McPike M., Gabuzda D.
Genes Dev. 18:2861-2866(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN CUL5 AND ELONGIN BC COMPLEX, MUTAGENESIS OF SER-144; LEU-145; GLN-146; TYR-147; LEU-148; ALA-149 AND LEU-150.
|||"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: INTERACTION WITH HUMAN APOBEC3G, MUTAGENESIS OF CYS-114 AND CYS-133.
|||"Ring finger protein ZIN interacts with human immunodeficiency virus type 1 Vif."|
Feng F., Davis A., Lake J.A., Carr J., Xia W., Burrell C., Li P.
J. Virol. 78:10574-10581(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN UBCE7IP1.
|||"Primate lentiviral virion infectivity factors are substrate receptors that assemble with cullin 5-E3 ligase through a HCCH motif to suppress APOBEC3G."|
Luo K., Xiao Z., Ehrlich E., Yu Y., Liu B., Zheng S., Yu X.-F.
Proc. Natl. Acad. Sci. U.S.A. 102:11444-11449(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN CUL5, MUTAGENESIS OF HIS-108; CYS-114; CYS-133 AND HIS-139.
|||"Nuclear localization of HIV type 1 Vif isolated from a long-term asymptomatic individual and potential role in virus attenuation."|
Farrow M.A., Somasundaran M., Zhang C., Gabuzda D., Sullivan J.L., Greenough T.C.
AIDS Res. Hum. Retroviruses 21:565-574(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT 90-LYS--LYS-93.
Strain: Clinical Isolate.
|||"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.
|+||Additional computationally mapped references.|
|M19921 Genomic RNA. Translation: AAA44989.1.|
M38431 Genomic RNA. Translation: AAB04038.1.
3D structure databases
Protein-protein interaction databases
|IntAct||P12504. 29 interactions.|
Protocols and materials 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: P12504|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|