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Protein

Virion infectivity factor

Gene

vif

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate NY5) (HIV-1)
Status
Reviewed-Annotation score: 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 (By similarity).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Host-virus interaction, Ubl conjugation pathway

Keywords - Ligandi

RNA-binding

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 NY5) (HIV-1)
Taxonomic identifieri11698 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi5 – 6WQ → AA: 44% loss of viral infectivity. 1 Publication2
Mutagenesisi12 – 13QV → AA: No effect on viral infectivity. 1 Publication2
Mutagenesisi16 – 18MRI → AAA: 29% loss of viral infectivity. 1 Publication3
Mutagenesisi23 – 24RL → AA: 14% loss of viral infectivity. 1 Publication2
Mutagenesisi29 – 31MYI → AAV: 59% loss of viral infectivity. 1 Publication3
Mutagenesisi33 – 34RK → AA: 35% loss of viral infectivity. 1 Publication2
Mutagenesisi38 – 40WFY → AAA: 94% loss of viral infectivity. 1 Publication3
Mutagenesisi43 – 44HY → AA: 95% loss of viral infectivity. 1 Publication2
Mutagenesisi53 – 54SE → AA: 39% loss of viral infectivity. 1 Publication2
Mutagenesisi58 – 59PL → AA: 45% loss of viral infectivity. 1 Publication2
Mutagenesisi69 – 70YW → AA: 97% loss of viral infectivity. 1 Publication2
Mutagenesisi73 – 74HT → AA: No effect onviral infectivity. 1 Publication2
Mutagenesisi80 – 81HL → AA: 19% loss of viral infectivity. 1 Publication2
Mutagenesisi86 – 87SI → AA: 42% loss of viral infectivity. 1 Publication2
Mutagenesisi90 – 92RKK → AAA: No effect on viral infectivity. 1 Publication3
Mutagenesisi97 – 98QV → AA: 27% loss of viral infectivity. 1 Publication2
Mutagenesisi105 – 107QLI → AAV: 98% loss of viral infectivity. 1 Publication3
Mutagenesisi108H → L: Complete loss of interaction with CUL5. 1 Publication1
Mutagenesisi111 – 112YF → AA: 93% loss of viral infectivity. 1 Publication2
Mutagenesisi114C → S: 98% loss of viral infectivity. Complete loss of interaction with CUL5. 3 Publications1
Mutagenesisi121 – 123RNT → AAA: 35% increase of viral infectivity. 1 Publication3
Mutagenesisi127 – 128RI → AA: 10% loss of viral infectivity. 1 Publication2
Mutagenesisi133C → S: 95% loss of viral infectivity. Complete loss of interaction with CUL5. 3 Publications1
Mutagenesisi135 – 136YQ → AA: 73% loss of viral infectivity. 1 Publication2
Mutagenesisi139H → L: Complete loss of interaction with CUL5. 1 Publication1
Mutagenesisi140 – 141NK → AA: 68% loss of viral infectivity. 1 Publication2
Mutagenesisi144 – 146SLQ → AAA: 93% loss of viral infectivity. 1 Publication3
Mutagenesisi144S → A: 25% loss of interaction with CUL5y. 1 Publication1
Mutagenesisi145L → A: Complete loss of interaction with CUL5. 1 Publication1
Mutagenesisi146Q → A: 90% loss of interaction with CUL5. 1 Publication1
Mutagenesisi147 – 148YL → AA: 40% loss of viral infectivity. 1 Publication2
Mutagenesisi147Y → A: 40% loss of interaction with CUL5. 1 Publication1
Mutagenesisi148L → A: 35% loss of interaction with CUL5. 1 Publication1
Mutagenesisi149 – 151ALA → RKS: Complete loss of processing between p17 and p7. Complete loss of replication. 1 Publication3
Mutagenesisi149A → G: 75% loss of CUL5 binding activity. 1 Publication1
Mutagenesisi150L → A: 90% loss of CUL5 binding activity. 1 Publication1
Mutagenesisi151A → E: No effect on processing between p17 and p7. 1
Mutagenesisi151A → N: Slightly increased processing between p17 and p7. 1
Mutagenesisi151A → P: Increased processing between p17 and p7. 1
Mutagenesisi151A → Y: Partial loss of processing between p17 and p7. 1
Mutagenesisi156 – 158PKQ → AAA: No effect on viral infectivity. 1 Publication3
Mutagenesisi157K → A: No effect viral infectivity. 1 Publication1
Mutagenesisi158 – 160QIK → AAA: 9% loss of viral infectivity. 1 Publication3
Mutagenesisi160K → A: 33% loss of viral infectivity. 1
Mutagenesisi161 – 164PPLP → APLA: 88% loss of viral infectivity. 1 Publication4
Mutagenesisi161 – 163PPL → AAA: 97% loss of viral infectivity. 3
Mutagenesisi161P → A: 27% loss of viral infectivity. 1
Mutagenesisi162P → A: No effect viral infectivity. 1
Mutagenesisi163L → A: 26% loss of viral infectivity. 1
Mutagenesisi164P → A: 63% loss of viral infectivity. 1
Mutagenesisi165S → A: 67% loss of viral infectivity. 1 Publication1
Mutagenesisi166V → A: 20% loss of viral infectivity. 1 Publication1
Mutagenesisi169 – 170LT → AA: 42% loss of viral infectivity. 1 Publication2
Mutagenesisi180 – 181TK → AA: 5% loss of viral infectivity. 1 Publication2
Mutagenesisi189 – 190MN → AA: 4% loss of viral infectivity. 1 Publication2

Keywords - Diseasei

AIDS

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000427621 – 192Virion infectivity factorAdd BLAST192
ChainiPRO_00000427631 – 150Virion infectivity factor p17Add BLAST150
ChainiPRO_0000042764151 – 192Virion infectivity factor p7Add BLAST42

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei96Phosphothreonine; by host MAP4K1By similarity1
Modified residuei144Phosphoserine; by hostBy similarity1
Modified residuei165Phosphoserine; by host MAP4K1By similarity1
Modified residuei188Phosphothreonine; by hostBy similarity1

Post-translational modificationi

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.1 Publication
Polyubiquitinated and degraded by the proteasome in the presence of APOBEC3G.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei150 – 151Cleavage in virion (by viral protease)2

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Expressioni

Inductioni

Expressed late during infection in a Rev-dependent manner.1 Publication

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 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
AMBRA1Q9C0C75EBI-779991,EBI-2512975From a different organism.
CBFBQ139515EBI-779991,EBI-718750From a different organism.
CUL2Q136175EBI-779991,EBI-456179From a different organism.
CUL5Q930345EBI-779991,EBI-1057139From a different organism.
DCAF11Q8TEB13EBI-779991,EBI-2213388From a different organism.
DNAJC7Q996153EBI-779991,EBI-357552From a different organism.
GPS2Q132272EBI-779991,EBI-713355From a different organism.
HCKP086313EBI-779991,EBI-346340From a different organism.
HDAC3O153792EBI-779991,EBI-607682From a different organism.
MAPK6Q166592EBI-779991,EBI-1384105From a different organism.
PSME3P612892EBI-779991,EBI-355546From a different organism.
RNF216Q9NWF9-34EBI-779991,EBI-723337From a different organism.
RNF7Q9UBF64EBI-779991,EBI-398632From a different organism.
SQSTM1Q135012EBI-779991,EBI-307104From a different organism.
STUB1Q9UNE72EBI-779991,EBI-357085From a different organism.
TCEB1Q153695EBI-779991,EBI-301231From a different organism.
TCEB2Q153705EBI-779991,EBI-301238From a different organism.
UBL4AP114412EBI-779991,EBI-356983From a different organism.
UBR2Q8IWV83EBI-779991,EBI-1237260From a different organism.

Protein-protein interaction databases

DIPiDIP-36069N.
IntActiP12504. 29 interactors.

Structurei

Secondary structure

1192
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 13Combined sources9
Helixi15 – 30Combined sources16
Turni34 – 37Combined sources4
Beta strandi39 – 41Combined sources3
Turni43 – 45Combined sources3
Beta strandi51 – 59Combined sources9
Beta strandi62 – 69Combined sources8
Beta strandi73 – 75Combined sources3
Beta strandi83 – 91Combined sources9
Beta strandi94 – 97Combined sources4
Helixi100 – 109Combined sources10
Helixi119 – 125Combined sources7
Helixi136 – 138Combined sources3
Helixi145 – 154Combined sources10
Helixi166 – 169Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MA9NMR-A139-174[»]
3DCGX-ray2.40E/F139-176[»]
4N9FX-ray3.301/2/7/G/M/S/b/d/j/p/q/v1-176[»]
ProteinModelPortaliP12504.
SMRiP12504.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP12504.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni14 – 17Interaction with host APOBEC3F; F1-boxBy similarity4
Regioni40 – 44Interaction with host APOBEC3G; G-boxBy similarity5
Regioni54 – 72Interaction with host APOBEC3F and APOBEC3G; FG-boxBy similarityAdd BLAST19
Regioni74 – 79Interaction with host APOBEC3F; F2-boxBy similarity6
Regioni75 – 114RNA-bindingSequence analysisAdd BLAST40
Regioni151 – 164MultimerizationAdd BLAST14
Regioni171 – 172Membrane association2

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi108 – 139HCCH motifAdd BLAST32
Motifi144 – 153BC-box-like motif10

Domaini

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.

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.

P12504-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MENRWQVMIV WQVDRMRINT WKRLVKHHMY ISRKAKDWFY RHHYESTNPK
60 70 80 90 100
ISSEVHIPLG DAKLVITTYW GLHTGERDWH LGQGVSIEWR KKRYSTQVDP
110 120 130 140 150
DLADQLIHLH YFDCFSESAI RNTILGRIVS PRCEYQAGHN KVGSLQYLAL
160 170 180 190
AALIKPKQIK PPLPSVRKLT EDRWNKPQKT KGHRGSHTMN GH
Length:192
Mass (Da):22,699
Last modified:October 1, 1989 - v1
Checksum:i2830B3233E8ECD16
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti90 – 93RKKR → KKRK in strain: Clinical isolate; from an asymptomatic patient; Vif is mislocalized to the nucleus and non functional. 4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M19921 Genomic RNA. Translation: AAA44989.1.
M38431 Genomic RNA. Translation: AAB04038.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M19921 Genomic RNA. Translation: AAA44989.1.
M38431 Genomic RNA. Translation: AAB04038.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MA9NMR-A139-174[»]
3DCGX-ray2.40E/F139-176[»]
4N9FX-ray3.301/2/7/G/M/S/b/d/j/p/q/v1-176[»]
ProteinModelPortaliP12504.
SMRiP12504.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-36069N.
IntActiP12504. 29 interactors.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP12504.

Family and domain databases

InterProiIPR000475. Viral_infect.
[Graphical view]
PfamiPF00559. Vif. 1 hit.
[Graphical view]
PRINTSiPR00349. VIRIONINFFCT.
ProtoNetiSearch...

Entry informationi

Entry nameiVIF_HV1N5
AccessioniPrimary (citable) accession number: P12504
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: November 2, 2016
This is version 102 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.
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).

Keywords - Technical termi

3D-structure, Direct protein sequencing

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.