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P12504 (VIF_HV1N5) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 95. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Virion infectivity factor

Short name=Vif
Alternative name(s):
SOR protein
Gene names
Name:vif
OrganismHuman immunodeficiency virus type 1 group M subtype B (isolate NY5) (HIV-1)
Taxonomic identifier11698 [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 By similarity. Ref.4 Ref.10

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 By similarity. Ref.6 Ref.7 Ref.8 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16

Subcellular location

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.

Induction

Expressed late during infection in a Rev-dependent manner. Ref.3

Domain

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.

Post-translational modification

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.

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).

Sequence similarities

Belongs to the primate lentivirus group Vif protein family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 192192Virion infectivity factor
PRO_0000042762
Chain1 – 150150Virion infectivity factor p17
PRO_0000042763
Chain151 – 19242Virion infectivity factor p7
PRO_0000042764

Regions

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

Sites

Site150 – 1512Cleavage in virion (by viral protease)

Amino acid modifications

Modified residue961Phosphothreonine; by host MAP4K1 By similarity
Modified residue1441Phosphoserine; by host By similarity
Modified residue1651Phosphoserine; by host MAP4K1 By similarity
Modified residue1881Phosphothreonine; by host By similarity

Natural variations

Natural variant90 – 934RKKR → KKRK in strain: Clinical isolate; from an asymptomatic patient; Vif is mislocalized to the nucleus and non functional.

Experimental info

Mutagenesis5 – 62WQ → AA: 44% loss of viral infectivity.
Mutagenesis12 – 132QV → AA: No effect on viral infectivity.
Mutagenesis16 – 183MRI → AAA: 29% loss of viral infectivity. Ref.5
Mutagenesis23 – 242RL → AA: 14% loss of viral infectivity.
Mutagenesis29 – 313MYI → AAV: 59% loss of viral infectivity. Ref.5
Mutagenesis33 – 342RK → AA: 35% loss of viral infectivity.
Mutagenesis38 – 403WFY → AAA: 94% loss of viral infectivity. Ref.5
Mutagenesis43 – 442HY → AA: 95% loss of viral infectivity.
Mutagenesis53 – 542SE → AA: 39% loss of viral infectivity.
Mutagenesis58 – 592PL → AA: 45% loss of viral infectivity.
Mutagenesis69 – 702YW → AA: 97% loss of viral infectivity.
Mutagenesis73 – 742HT → AA: No effect onviral infectivity.
Mutagenesis80 – 812HL → AA: 19% loss of viral infectivity.
Mutagenesis86 – 872SI → AA: 42% loss of viral infectivity.
Mutagenesis90 – 923RKK → AAA: No effect on viral infectivity. Ref.5
Mutagenesis97 – 982QV → AA: 27% loss of viral infectivity.
Mutagenesis105 – 1073QLI → AAV: 98% loss of viral infectivity. Ref.5
Mutagenesis1081H → L: Complete loss of interaction with CUL5. Ref.16
Mutagenesis111 – 1122YF → AA: 93% loss of viral infectivity.
Mutagenesis1141C → S: 98% loss of viral infectivity. Complete loss of interaction with CUL5. Ref.5 Ref.14 Ref.16
Mutagenesis121 – 1233RNT → AAA: 35% increase of viral infectivity. Ref.5
Mutagenesis127 – 1282RI → AA: 10% loss of viral infectivity.
Mutagenesis1331C → S: 95% loss of viral infectivity. Complete loss of interaction with CUL5. Ref.5 Ref.14 Ref.16
Mutagenesis135 – 1362YQ → AA: 73% loss of viral infectivity.
Mutagenesis1391H → L: Complete loss of interaction with CUL5. Ref.16
Mutagenesis140 – 1412NK → AA: 68% loss of viral infectivity.
Mutagenesis144 – 1463SLQ → AAA: 93% loss of viral infectivity. Ref.5 Ref.13
Mutagenesis1441S → A: 25% loss of interaction with CUL5y. Ref.13
Mutagenesis1451L → A: Complete loss of interaction with CUL5. Ref.13
Mutagenesis1461Q → A: 90% loss of interaction with CUL5. Ref.13
Mutagenesis147 – 1482YL → AA: 40% loss of viral infectivity. Ref.13
Mutagenesis1471Y → A: 40% loss of interaction with CUL5. Ref.13
Mutagenesis1481L → A: 35% loss of interaction with CUL5. Ref.13
Mutagenesis149 – 1513ALA → RKS: Complete loss of processing between p17 and p7. Complete loss of replication. Ref.9 Ref.13
Mutagenesis1491A → G: 75% loss of CUL5 binding activity. Ref.13
Mutagenesis1501L → A: 90% loss of CUL5 binding activity. Ref.13
Mutagenesis1511A → E: No effect on processing between p17 and p7.
Mutagenesis1511A → N: Slightly increased processing between p17 and p7.
Mutagenesis1511A → P: Increased processing between p17 and p7.
Mutagenesis1511A → Y: Partial loss of processing between p17 and p7.
Mutagenesis156 – 1583PKQ → AAA: No effect on viral infectivity. Ref.5
Mutagenesis1571K → A: No effect viral infectivity. Ref.5
Mutagenesis158 – 1603QIK → AAA: 9% loss of viral infectivity. Ref.5
Mutagenesis1601K → A: 33% loss of viral infectivity.
Mutagenesis161 – 1644PPLP → APLA: 88% loss of viral infectivity. Ref.5
Mutagenesis161 – 1633PPL → AAA: 97% loss of viral infectivity.
Mutagenesis1611P → A: 27% loss of viral infectivity.
Mutagenesis1621P → A: No effect viral infectivity.
Mutagenesis1631L → A: 26% loss of viral infectivity.
Mutagenesis1641P → A: 63% loss of viral infectivity.
Mutagenesis1651S → A: 67% loss of viral infectivity. Ref.5
Mutagenesis1661V → A: 20% loss of viral infectivity. Ref.5
Mutagenesis169 – 1702LT → AA: 42% loss of viral infectivity.
Mutagenesis180 – 1812TK → AA: 5% loss of viral infectivity.
Mutagenesis189 – 1902MN → AA: 4% loss of viral infectivity.

Secondary structure

............................... 192
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P12504 [UniParc].

Last modified October 1, 1989. Version 1.
Checksum: 2830B3233E8ECD16

FASTA19222,699
        10         20         30         40         50         60 
MENRWQVMIV WQVDRMRINT WKRLVKHHMY ISRKAKDWFY RHHYESTNPK ISSEVHIPLG 

        70         80         90        100        110        120 
DAKLVITTYW GLHTGERDWH LGQGVSIEWR KKRYSTQVDP DLADQLIHLH YFDCFSESAI 

       130        140        150        160        170        180 
RNTILGRIVS PRCEYQAGHN KVGSLQYLAL AALIKPKQIK PPLPSVRKLT EDRWNKPQKT 

       190 
KGHRGSHTMN GH 

« Hide

References

[1]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.
[2]Theodore T., Buckler-White A.J.
Submitted (OCT-1992) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]"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.
[4]"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.
[5]"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.
[6]"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.
[7]"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.
[8]"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.
[9]"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.
[10]"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.
[11]"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.
[12]"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.
[13]"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.
[14]"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.
[15]"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.
[16]"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.
[17]"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.
[18]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M19921 Genomic RNA. Translation: AAA44989.1.
M38431 Genomic RNA. Translation: AAB04038.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2MA9NMR-A143-174[»]
3DCGX-ray2.40E/F139-176[»]
4N9FX-ray3.301/2/7/G/M/S/b/d/j/p/q/v1-176[»]
ProteinModelPortalP12504.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-36069N.
IntActP12504. 29 interactions.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

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

Other

EvolutionaryTraceP12504.

Entry information

Entry nameVIF_HV1N5
AccessionPrimary (citable) accession number: P12504
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: July 9, 2014
This is version 95 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references