P31820 · VIF_HV1NA
- ProteinVirion infectivity factor
- Genevif
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids192 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score4/5
Function
function
Counteracts the innate antiviral activity of host APOBEC3F and APOBEC3G by promoting their ubiquitination and degradation. Acts as a substrate recognition component of an E3 ubiquitin-protein ligase complex: mechanistically, Vif hijacks a host cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) and the transcription coactivator CBFB/CBF-beta to form an active E3 ubiquitin-protein ligase complex that targets APOBEC3G and APOBEC3F for polyubiquitination, leading to their degradation by the proteasome. 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. Association with CBFB/CBF-beta also inhibits the transcription coactivator activity of CBFB/CBF-beta. 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.
Miscellaneous
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).
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.
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Binding site | 108 | Zn2+ (UniProtKB | ChEBI) | |||
Binding site | 114 | Zn2+ (UniProtKB | ChEBI) | |||
Binding site | 133 | Zn2+ (UniProtKB | ChEBI) | |||
Binding site | 139 | Zn2+ (UniProtKB | ChEBI) | |||
Site | 150-151 | Cleavage in virion (by viral protease) | |||
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | host cell cytoplasm | |
Cellular Component | host cell plasma membrane | |
Cellular Component | membrane | |
Cellular Component | virion component | |
Molecular Function | metal ion binding | |
Molecular Function | RNA binding | |
Biological Process | viral life cycle |
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameVirion infectivity factor
- Short namesVif
- Alternative names
- Cleaved into 2 chains
Gene names
Organism names
- Taxonomic lineageViruses > Riboviria > Pararnavirae > Artverviricota > Revtraviricetes > Ortervirales > Retroviridae > Orthoretrovirinae > Lentivirus > Human immunodeficiency virus type 1
- Virus hosts
Accessions
- Primary accessionP31820
Subcellular Location
UniProt Annotation
GO Annotation
Host cell membrane ; Peripheral membrane protein
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.
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Mutagenesis | 114 | Complete loss of viral infectivity in non-permissive cells. | |||
Mutagenesis | 133 | Complete loss of viral infectivity in non-permissive cells. | |||
Keywords
- Disease
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000043033 | 1-150 | p17 | ||
Chain | PRO_0000043032 | 1-192 | Virion infectivity factor | ||
Modified residue | 96 | Phosphothreonine; by host MAP4K1 | |||
Modified residue | 144 | Phosphoserine; by host | |||
Chain | PRO_0000043034 | 151-192 | p7 | ||
Modified residue | 155 | Phosphothreonine; by host | |||
Modified residue | 165 | Phosphoserine; by host MAP4K1 | |||
Modified residue | 188 | Phosphothreonine; by host | |||
Post-translational modification
Processed in virion by the viral protease.
Highly phosphorylated on serine and threonine residues.
Polyubiquitinated and degraded by the proteasome in the presence of APOBEC3G.
Keywords
- PTM
Expression
Induction
Expressed late during infection in a Rev-dependent manner.
Interaction
Subunit
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. Forms cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) by interacting with host CUL5, RBX2, elongin BC complex (ELOB and ELOC) and CBFB/CBF-beta. Within the ECS complex, Vif interacts directly with host CUL5, ELOC and APOBEC (APOBEC3F and APOBEC3G) substrates. The ECS complex also contains some single-stranded RNA (ssRNA) that acts as a glue that bridges Vif with APOBEC (APOBEC3F and APOBEC3G) substrates. 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. Interacts with host MDM2; this interaction targets Vif for degradation by the proteasome.
Family & Domains
Features
Showing features for region, motif.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Region | 14-17 | Interaction with host APOBEC3F; F1-box | |||
Region | 40-44 | Interaction with host APOBEC3G; G-box | |||
Region | 54-72 | Interaction with host APOBEC3F and APOBEC3G; FG-box | |||
Region | 74-79 | Interaction with host APOBEC3F; F2-box | |||
Region | 75-114 | RNA-binding | |||
Motif | 108-139 | HCCH motif | |||
Motif | 144-153 | BC-box-like motif | |||
Region | 151-164 | Multimerization | |||
Region | 151-180 | SOCS box-like | |||
Region | 164-192 | Disordered | |||
Region | 171-172 | Membrane association | |||
Domain
The BC-like-box motif mediates the interaction with elongin BC complex.
The HCCH motif (H-x5-C-x18-C-x5-H) mediates the interaction with CUL5.
Sequence similarities
Belongs to the primate lentivirus group Vif protein family.
Family and domain databases
Sequence
- Sequence statusComplete
- Length192
- Mass (Da)22,611
- Last updated1993-07-01 v1
- MD5 ChecksumDD4EE8F378779B4389E053826C294DA6