P69720 (VIF_HV1B1) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 55. History...
Names and origin
|Protein names||Recommended name:|
Virion infectivity factor
|Organism||Human immunodeficiency virus type 1 group M subtype B (isolate BH10) (HIV-1) [Complete proteome]|
|Taxonomic identifier||11678 [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 transcript 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.
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.
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.
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 By similarity.
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||PRO_0000085312|
|Chain||1 – 150||150||p17||PRO_0000244708|
|Chain||151 – 192||42||p7||PRO_0000244709|
|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 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 By similarity|
|Modified residue||144||1||Phosphoserine; by host By similarity|
|Modified residue||155||1||Phosphothreonine; by host By similarity|
|Modified residue||165||1||Phosphoserine; by host MAP4K1 By similarity|
|Modified residue||188||1||Phosphothreonine; by host By similarity|
|||"Complete nucleotide sequence of the AIDS virus, HTLV-III."|
Ratner L., Haseltine W.A., Patarca R., Livak K.J., Starcich B.R., Josephs S.F., Doran E.R., Rafalski J.A., Whitehorn E.A., Baumeister K., Ivanoff L., Petteway S.R. Jr., Pearson M.L., Lautenberger J.A., Papas T.S., Ghrayeb J., Chang N.T., Gallo R.C., Wong-Staal F.
Nature 313:277-284(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus."|
Muesing M.A., Smith D.H., Cabradilla C.D., Benton C.V., Lasky L.A., Capon D.J.
Nature 313:450-458(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: Isolate PV22.
|+||Additional computationally mapped references.|
|M15654 Genomic RNA. Translation: AAA44202.1.|
K02083 Genomic DNA. Translation: AAB59868.1.
X01762 Genomic RNA. No translation available.
|RefSeq||NP_057851.1. NC_001802.1. |
3D structure databases
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: P69720|
Secondary accession number(s): P03401, P69724
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|
Index of protein domains and families