[1]	NUCLEOTIDE SEQUENCE [GENOMIC RNA]. STRAIN=Clone pNL4-3; Buckler C.E., Buckler-White A.J., Willey R.L., McCoy J.; Submitted (JUN-1988) to the EMBL/GenBank/DDBJ databases.
[2]	NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Theodore T., Buckler-White A.J.; Submitted (OCT-1992) to the EMBL/GenBank/DDBJ databases.
[3]	INDUCTION. DOI=10.1016/0042-6822(91)90996-O; PubMed=1830183 [NCBI, ExPASy, EBI, Israel, Japan] Schwartz S., Felber B.K., Pavlakis G.N.; "Expression of human immunodeficiency virus type 1 vif and vpr mRNAs is Rev-dependent and regulated by splicing."; Virology 183:677-686(1991).
[4]	ROLE IN VIRION MORPHOLOGY. DOI=10.1006/viro.1994.1300; PubMed=8184544 [NCBI, ExPASy, EBI, Israel, Japan] Hoglund S., Ohagen A., Lawrence K., Gabuzda D.; "Role of vif during packing of the core of HIV-1."; Virology 201:349-355(1994).
[5]	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. PubMed=10074113 [NCBI, ExPASy, EBI, Israel, Japan] Simon J.H., Sheehy A.M., Carpenter E.A., Fouchier R.A., Malim M.H.; "Mutational analysis of the human immunodeficiency virus type 1 Vif protein."; J. Virol. 73:2675-2681(1999).
[6]	MULTIMERIZATION. DOI=10.1074/jbc.M004895200; PubMed=11071884 [NCBI, ExPASy, EBI, Israel, Japan] Yang S., Sun Y., Zhang H.; "The multimerization of human immunodeficiency virus type I Vif protein: a requirement for Vif function in the viral life cycle."; J. Biol. Chem. 276:4889-4893(2001).
[7]	INTERACTION WITH NUCLEOPROTEIN. DOI=10.1128/JVI.75.16.7252-7265.2001; PubMed=11461998 [NCBI, ExPASy, EBI, Israel, Japan] Khan M.A., Aberham C., Kao S., Akari H., Gorelick R., Bour S., Strebel K.; "Human immunodeficiency virus type 1 Vif protein is packaged into the nucleoprotein complex through an interaction with viral genomic RNA."; J. Virol. 75:7252-7265(2001).
[8]	INTERACTION WITH HUMAN HCK. DOI=10.1074/jbc.M009076200; PubMed=11278465 [NCBI, ExPASy, EBI, Israel, Japan] Hassaine G., Courcoul M., Bessou G., Barthalay Y., Picard C., Olive D., Collette Y., Vigne R., Decroly E.; "The tyrosine kinase Hck is an inhibitor of HIV-1 replication counteracted by the viral vif protein."; J. Biol. Chem. 276:16885-16893(2001).
[9]	PROTEIN SEQUENCE OF 2-9 AND 151-162, CLEAVAGE BY VIRAL PROTEASE, AND MUTAGENESIS OF 149-ALA--ALA-151. DOI=10.1128/JVI.76.18.9112-9123.2002; PubMed=12186895 [NCBI, ExPASy, EBI, Israel, Japan] Khan M.A., Akari H., Kao S., Aberham C., Davis D., Buckler-White A., Strebel K.; "Intravirion processing of the human immunodeficiency virus type 1 Vif protein by the viral protease may be correlated with Vif function."; J. Virol. 76:9112-9123(2002).
[10]	FUNCTION. DOI=10.1128/JVI.77.21.11398-11407.2003; PubMed=14557625 [NCBI, ExPASy, EBI, Israel, Japan] Kao S., Khan M.A., Miyagi E., Plishka R., Buckler-White A., Strebel K.; "The human immunodeficiency virus type 1 Vif protein reduces intracellular expression and inhibits packaging of APOBEC3G (CEM15), a cellular inhibitor of virus infectivity."; J. Virol. 77:11398-11407(2003).
[11]	INTERACTION WITH HUMAN SAT. DOI=10.1016/S1386-6532(02)00113-0; PubMed=12600646 [NCBI, ExPASy, EBI, Israel, Japan] Lake J.A., Carr J., Feng F., Mundy L., Burrell C., Li P.; "The role of Vif during HIV-1 infection: interaction with novel host cellular factors."; J. Clin. Virol. 26:143-152(2003).
[12]	INTERACTION WITH HUMAN APOBEC3G. DOI=10.1038/nm946; PubMed=14528301 [NCBI, ExPASy, EBI, Israel, Japan] Marin M., Rose K.M., Kozak S.L., Kabat D.; "HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation."; Nat. Med. 9:1398-1403(2003).
[13]	INTERACTION WITH HUMAN CUL5 AND ELONGIN BC COMPLEX, AND MUTAGENESIS OF SER-144; LEU-145; GLN-146; TYR-147; LEU-148; ALA-149 AND LEU-150. DOI=10.1101/gad.1249904; PubMed=15574592 [NCBI, ExPASy, EBI, Israel, Japan] Mehle A., Goncalves J., Santa-Marta M., McPike M., Gabuzda D.; "Phosphorylation of a novel SOCS-box regulates assembly of the HIV-1 Vif-Cul5 complex that promotes APOBEC3G degradation."; Genes Dev. 18:2861-2866(2004).
[14]	INTERACTION WITH HUMAN APOBEC3G, AND MUTAGENESIS OF CYS-114 AND CYS-133. DOI=10.1074/jbc.M313093200; PubMed=14672928 [NCBI, ExPASy, EBI, Israel, Japan] Mehle A., Strack B., Ancuta P., Zhang C., McPike M., Gabuzda D.; "Vif overcomes the innate antiviral activity of APOBEC3G by promoting its degradation in the ubiquitin-proteasome pathway."; J. Biol. Chem. 279:7792-7798(2004).
[15]	INTERACTION WITH HUMAN UBCE7IP1. DOI=10.1128/JVI.78.19.10574-10581.2004; PubMed=15367624 [NCBI, ExPASy, EBI, Israel, Japan] Feng F., Davis A., Lake J.A., Carr J., Xia W., Burrell C., Li P.; "Ring finger protein ZIN interacts with human immunodeficiency virus type 1 Vif."; J. Virol. 78:10574-10581(2004).
[16]	INTERACTION WITH HUMAN CUL5, AND MUTAGENESIS OF HIS-108; CYS-114; CYS-133 AND HIS-139. DOI=10.1073/pnas.0502440102; PubMed=16076960 [NCBI, ExPASy, EBI, Israel, Japan] Luo K., Xiao Z., Ehrlich E., Yu Y., Liu B., Zheng S., Yu X.-F.; "Primate lentiviral virion infectivity factors are substrate receptors that assemble with cullin 5-E3 ligase through a HCCH motif to suppress APOBEC3G."; Proc. Natl. Acad. Sci. U.S.A. 102:11444-11449(2005).
[17]	VARIANT 90-LYS--LYS-93. STRAIN=Clinical Isolate; DOI=10.1089/aid.2005.21.565; PubMed=15989462 [NCBI, ExPASy, EBI, Israel, Japan] Farrow M.A., Somasundaran M., Zhang C., Gabuzda D., Sullivan J.L., Greenough T.C.; "Nuclear localization of HIV type 1 Vif isolated from a long-term asymptomatic individual and potential role in virus attenuation."; AIDS Res. Hum. Retroviruses 21:565-574(2005).
[18]	REVIEW. DOI=10.1016/j.molmed.2004.04.008; PubMed=15177194 [NCBI, ExPASy, EBI, Israel, Japan] Rose K.M., Marin M., Kozak S.L., Kabat D.; "The viral infectivity factor (Vif) of HIV-1 unveiled."; Trends Mol. Med. 10:291-297(2004).

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: 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).
INTERACTION:
Q9HC16:APOBEC3G (xeno); NbExp=1; IntAct=EBI-779991, EBI-717839;
P08631:HCK (xeno); NbExp=3; IntAct=EBI-779991, EBI-346340;
Q9NWF9-3:UBCE7IP1 (xeno); NbExp=2; IntAct=EBI-779991, EBI-723337;
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.
DOMAIN: The HCCH motif (H-x(5)-C-x(18)-C-x(5)-H) mediates the interaction with CUL5.
PTM: Processed in virion by the viral protease.
PTM: 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.
PTM: 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.
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.
MISCELLANEOUS: The infectious clone pNL4-3 is a chimeric provirus that consists of DNA from HIV isolates NY5 (5' half) and BRU (3' half).
MISCELLANEOUS: 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).
SIMILARITY: Belongs to the primate lentivirus group Vif protein family.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M19921; AAA44989.1; -; Genomic_RNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M38431; AAB04038.1; -; Genomic_RNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

3D structure databases

ModBase

P12504.

Protein-protein interaction databases

IntAct

P12504; -.

Enzyme and pathway databases

Reactome

REACT_6185; HIV Infection.

Ontologies

GO:0005829;	Cellular component: cytosol (inferred from experiment from Reactome).
GO:0005515;	Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0019059;	Biological process: initiation of viral infection (inferred from experiment from Reactome).
GO:0019047;	Biological process: provirus integration (inferred from experiment from Reactome).
QuickGo view.

Family and domain databases

InterPro

IPR000475; Viral_infect.
Graphical view of domain structure.

Pfam

PF00559; Vif; 1.
Pfam graphical view of domain structure.

PRINTS

PR00349; VIRIONINFFCT.

ProDom

PD000063; Viral_infect; 1.
[Domain structure / List of seq. sharing at least 1 domain]

Other

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

AIDS; Cell membrane; Cytoplasm; Direct protein sequencing; Host-virus interaction; Membrane; Phosphoprotein; RNA-binding; Ubl conjugation; Ubl conjugation pathway; Virion.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 192`	`192`	`Virion infectivity factor.`	`PRO_0000042762`
`CHAIN`	`1 150`	`150`	`Virion infectivity factor p17.`	`PRO_0000042763`
`CHAIN`	`151 192`	`42`	`Virion infectivity factor p7.`	`PRO_0000042764`
`REGION`	`75 114`	`40`	`RNA-binding (Potential).`
`REGION`	`151 164`	`14`	`Multimerization.`
`REGION`	`171 172`	`2`	`Membrane association.`
`MOTIF`	`108 139`	`32`	`HCCH motif.`
`MOTIF`	`144 153`	`10`	`BC-box-like motif.`
`SITE`	`150 151`	`2`	`Cleavage in virion (by viral protease).`
`MOD_RES`	`96 96`		`Phosphothreonine; by MAP4K1 (By similarity).`
`MOD_RES`	`144 144`		`Phosphoserine (By similarity).`
`MOD_RES`	`165 165`		`Phosphoserine; by MAP4K1 (By similarity).`
`MOD_RES`	`188 188`		`Phosphothreonine (By similarity).`
`VARIANT`	`90 93`	`4`	`RKKR -> KKRK (in strain: Clinical isolate; from an asymptomatic patient; Vif is mislocalized to the nucleus and non functional).`
`MUTAGEN`	`5 6`		`WQ->AA: 44% loss of viral infectivity.`
`MUTAGEN`	`12 13`		`QV->AA: No effect on viral infectivity.`
`MUTAGEN`	`16 18`		`MRI->AAA: 29% loss of viral infectivity.`
`MUTAGEN`	`23 24`		`RL->AA: 14% loss of viral infectivity.`
`MUTAGEN`	`29 31`		`MYI->AAV: 59% loss of viral infectivity.`
`MUTAGEN`	`33 34`		`RK->AA: 35% loss of viral infectivity.`
`MUTAGEN`	`38 40`		`WFY->AAA: 94% loss of viral infectivity.`
`MUTAGEN`	`43 44`		`HY->AA: 95% loss of viral infectivity.`
`MUTAGEN`	`53 54`		`SE->AA: 39% loss of viral infectivity.`
`MUTAGEN`	`58 59`		`PL->AA: 45% loss of viral infectivity.`
`MUTAGEN`	`69 70`		`YW->AA: 97% loss of viral infectivity.`
`MUTAGEN`	`73 74`		`HT->AA: No effect onviral infectivity.`
`MUTAGEN`	`80 81`		`HL->AA: 19% loss of viral infectivity.`
`MUTAGEN`	`86 87`		`SI->AA: 42% loss of viral infectivity.`
`MUTAGEN`	`90 92`		`RKK->AAA: No effect on viral infectivity.`
`MUTAGEN`	`97 98`		`QV->AA: 27% loss of viral infectivity.`
`MUTAGEN`	`105 107`		`QLI->AAV: 98% loss of viral infectivity.`
`MUTAGEN`	`108 108`		`H->L: Complete loss of interaction with CUL5.`
`MUTAGEN`	`111 112`		`YF->AA: 93% loss of viral infectivity.`
`MUTAGEN`	`114 114`		`C->S: 98% loss of viral infectivity. Complete loss of interaction with CUL5.`
`MUTAGEN`	`121 123`		`RNT->AAA: 35% increase of viral infectivity.`
`MUTAGEN`	`127 128`		`RI->AA: 10% loss of viral infectivity.`
`MUTAGEN`	`133 133`		`C->S: 95% loss of viral infectivity. Complete loss of interaction with CUL5.`
`MUTAGEN`	`135 136`		`YQ->AA: 73% loss of viral infectivity.`
`MUTAGEN`	`139 139`		`H->L: Complete loss of interaction with CUL5.`
`MUTAGEN`	`140 141`		`NK->AA: 68% loss of viral infectivity.`
`MUTAGEN`	`144 146`		`SLQ->AAA: 93% loss of viral infectivity.`
`MUTAGEN`	`144 144`		`S->A: 25% loss of interaction with CUL5y.`
`MUTAGEN`	`145 145`		`L->A: Complete loss of interaction with CUL5.`
`MUTAGEN`	`146 146`		`Q->A: 90% loss of interaction with CUL5.`
`MUTAGEN`	`147 148`		`YL->AA: 40% loss of viral infectivity.`
`MUTAGEN`	`147 147`		`Y->A: 40% loss of interaction with CUL5.`
`MUTAGEN`	`148 148`		`L->A: 35% loss of interaction with CUL5.`
`MUTAGEN`	`149 151`		`ALA->RKS: Complete loss of processing between p17 and p7. Complete loss of replication.`
`MUTAGEN`	`149 149`		`A->G: 75% loss of CUL5 binding activity.`
`MUTAGEN`	`150 150`		`L->A: 90% loss of CUL5 binding activity.`
`MUTAGEN`	`151 151`		`A->E: No effect on processing between p17 and p7.`
`MUTAGEN`	`151 151`		`A->N: Slightly increased processing between p17 and p7.`
`MUTAGEN`	`151 151`		`A->P: Increased processing between p17 and p7.`
`MUTAGEN`	`151 151`		`A->Y: Partial loss of processing between p17 and p7.`
`MUTAGEN`	`156 158`		`PKQ->AAA: No effect on viral infectivity.`
`MUTAGEN`	`157 157`		`K->A: No effect viral infectivity.`
`MUTAGEN`	`158 160`		`QIK->AAA: 9% loss of viral infectivity.`
`MUTAGEN`	`160 160`		`K->A: 33% loss of viral infectivity.`
`MUTAGEN`	`161 164`		`PPLP->APLA: 88% loss of viral infectivity.`
`MUTAGEN`	`161 163`		`PPL->AAA: 97% loss of viral infectivity.`
`MUTAGEN`	`161 161`		`P->A: 27% loss of viral infectivity.`
`MUTAGEN`	`162 162`		`P->A: No effect viral infectivity.`
`MUTAGEN`	`163 163`		`L->A: 26% loss of viral infectivity.`
`MUTAGEN`	`164 164`		`P->A: 63% loss of viral infectivity.`
`MUTAGEN`	`165 165`		`S->A: 67% loss of viral infectivity.`
`MUTAGEN`	`166 166`		`V->A: 20% loss of viral infectivity.`
`MUTAGEN`	`169 170`		`LT->AA: 42% loss of viral infectivity.`
`MUTAGEN`	`180 181`		`TK->AA: 5% loss of viral infectivity.`
`MUTAGEN`	`189 190`		`MN->AA: 4% loss of viral infectivity.`

Sequence information

Length: 192 AA [This is the length of the unprocessed precursor]

Molecular weight: 22699 Da [This is the MW of the unprocessed precursor]

CRC64: 2830B3233E8ECD16 [This is a checksum on the sequence]

        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

P12504 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools