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Reviewed, UniProtKB/Swiss-Prot P12504 (VIF_HV1N5)

Last modified November 25, 2008. Version 57. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Virion infectivity factor
      Short name=Vif
Alternative name(s):
    SOR protein
Cleaved into the following 2 chains:
    1- Recommended name:
            Virion infectivity factor p17
    2- Recommended name:
            Virion infectivity factor p7
Gene names
Name: vif
OrganismHuman immunodeficiency virus type 1 (isolate NY5 group M subtype B) (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 not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Counteracts the innate antiviral activity of APOBEC3G. Forms a complex with host APOBEC3G thus preventing the entry of this lethally hypermutating enzyme into progeny virions. Functions as an adapter molecule, recruiting APOBEC3G to the ubiquitin-proteasome machinery. Targets APOBEC3G for degradation through the assembly with elongin BC complex, CUL5 and RBX1. Binds viral RNA and affects the stability of viral nucleoprotein core. May play a role in viral morphology. Interacts with host ABCE1, which seems to be involved in lentiviruses capsid formation and displays RNase L inhibitor activity. This interaction may play a role in protecting viral RNA from damage during viral assembly. May interact with host SAT, which is a regulator of polyamine cell level. This interaction may be relevant since polyamines affect viral RNA properties.

Subunit structure

Homomultimer; in vitro and presumably in vivo. Interacts with viral Pr55Gag precursor, human APOBEC3G, UBCE7IP1 isoform 3/ZIN, ABCE1 and possibly with SAT. Binds human HCK in vitro, but since this protein does not seem to be expressed in CD4+ cells, the significance of this interaction remains unclear. The interaction between Vif and APOBEC3G is species-specific, which may play a role in restricting the replication of HIV to humans. Forms an E3 ligase complex by interacting with human CUL5 and elongin BC complex (TCEB1 and TCEB2).

Subcellular location

Cytoplasm. 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.

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

APOBEC3GQ9HC161EBI-779991,EBI-717839From a different organism.
HCKP086313EBI-779991,EBI-346340From a different organism.
RNF216Q9NWF9-32EBI-779991,EBI-723337From 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

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 MAP4K1 By similarity
Modified residue1441Phosphoserine By similarity
Modified residue1651Phosphoserine; by MAP4K1 By similarity
Modified residue1881Phosphothreonine 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
Mutagenesis23 – 242RL → AA: 14% loss of viral infectivity
Mutagenesis29 – 313MYI → AAV: 59% loss of viral infectivity
Mutagenesis33 – 342RK → AA: 35% loss of viral infectivity
Mutagenesis38 – 403WFY → AAA: 94% loss of viral infectivity
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
Mutagenesis97 – 982QV → AA: 27% loss of viral infectivity
Mutagenesis105 – 1073QLI → AAV: 98% loss of viral infectivity
Mutagenesis1081H → L: Complete loss of interaction with CUL5
Mutagenesis111 – 1122YF → AA: 93% loss of viral infectivity
Mutagenesis1141C → S: 98% loss of viral infectivity. Complete loss of interaction with CUL5
Mutagenesis121 – 1233RNT → AAA: 35% increase of viral infectivity
Mutagenesis127 – 1282RI → AA: 10% loss of viral infectivity
Mutagenesis1331C → S: 95% loss of viral infectivity. Complete loss of interaction with CUL5
Mutagenesis135 – 1362YQ → AA: 73% loss of viral infectivity
Mutagenesis1391H → L: Complete loss of interaction with CUL5
Mutagenesis140 – 1412NK → AA: 68% loss of viral infectivity
Mutagenesis144 – 1463SLQ → AAA: 93% loss of viral infectivity
Mutagenesis1441S → A: 25% loss of interaction with CUL5y
Mutagenesis1451L → A: Complete loss of interaction with CUL5
Mutagenesis1461Q → A: 90% loss of interaction with CUL5
Mutagenesis147 – 1482YL → AA: 40% loss of viral infectivity
Mutagenesis1471Y → A: 40% loss of interaction with CUL5
Mutagenesis1481L → A: 35% loss of interaction with CUL5
Mutagenesis149 – 1513ALA → RKS: Complete loss of processing between p17 and p7. Complete loss of replication
Mutagenesis1491A → G: 75% loss of CUL5 binding activity
Mutagenesis1501L → A: 90% loss of CUL5 binding activity
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
Mutagenesis1571K → A: No effect viral infectivity
Mutagenesis158 – 1603QIK → AAA: 9% loss of viral infectivity
Mutagenesis1601K → A: 33% loss of viral infectivity
Mutagenesis161 – 1644PPLP → APLA: 88% loss of viral infectivity
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
Mutagenesis1661V → A: 20% loss of viral infectivity
Mutagenesis169 – 1702LT → AA: 42% loss of viral infectivity
Mutagenesis180 – 1812TK → AA: 5% loss of viral infectivity
Mutagenesis189 – 1902MN → AA: 4% loss of viral infectivity

Sequences

Sequence LengthMass (Da)Tools
P12504-1 [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: 1830183] [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: 8184544] [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: 10074113] [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: 11071884] [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: 11461998] [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: 11278465] [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: 12186895] [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: 14557625] [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: 12600646] [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: 14528301] [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: 15574592] [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: 14672928] [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: 15367624] [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: 16076960] [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: 15989462] [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: 15177194] [Abstract]
Cited for: REVIEW.
+Additional computationally mapped references.

Cross-references

Sequence databases

M19921 Genomic RNA. Translation: AAA44989.1.
M38431 Genomic RNA. Translation: AAB04038.1.

3D structure databases