Virion infectivity factor - Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)

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P69723 (VIF_HV1H2) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 62. History...

Clusters with 100%, 90%, 50% identity |

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Virion infectivity factor
Short name=Vif

Alternative name(s):
SOR protein

Cleaved into the following 2 chains:

Gene names

Name:

vif

Organism

Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1) [Reference proteome]

Taxonomic identifier

11706 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Lentivirus › Primate lentivirus group ›

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	192 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. Ref.6 Ref.10 Ref.11 Ref.15 Ref.19
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/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. Ref.8 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18
Subcellular location	Host cytoplasm By similarity. Host cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Virion By similarity. 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 By similarity. Ref.2 Ref.4
Induction	Expressed late during infection in a Rev-dependent manner.
Domain	The BC-like-box motif mediates the interaction with elongin BC complex By similarity. The HCCH motif (H-x(5)-C-x(18)-C-x(5)-H) mediates the interaction with CUL5 By similarity.
Post-translational modification	Processed in virion by the viral protease By similarity. 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. Ref.5 Ref.9 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. 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.

Ontologies

Keywords
Biological process	Host-virus interaction Ubl conjugation pathway
Cellular component	Host cell membrane Host cytoplasm Host membrane Membrane Virion
Disease	AIDS
Ligand	RNA-binding
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	RNA-dependent DNA replication Traceable author statement. Source: Reactome entry into host cell Traceable author statement. Source: Reactome uncoating of virus Traceable author statement. Source: Reactome viral infectious cycle Inferred from electronic annotation. Source: InterPro virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleoplasm Traceable author statement. Source: Reactome virion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 192

192

Virion infectivity factor By similarity

PRO_0000042759

Chain

1 – 150

150

p17 By similarity

PRO_0000042760

Chain

151 – 192

p7 By similarity

PRO_0000042761

Regions

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 Potential

Region

151 – 164

Multimerization By similarity

Region

171 – 172

Membrane association By similarity

Motif

108 – 139

HCCH motif By similarity

Motif

144 – 153

BC-box-like motif

Sites

Site

150 – 151

Cleavage in virion (by viral protease) By similarity

Amino acid modifications

Modified residue

Phosphothreonine; by host MAP4K1 Probable

Modified residue

144

Phosphoserine; by host

Modified residue

155

Phosphothreonine; by host

Modified residue

165

Phosphoserine; by host MAP4K1 Probable

Modified residue

188

Phosphothreonine; by host

Experimental info

Mutagenesis

T → A: 90% loss of reverse transcriptase activity in virions; no effect on the ability to decrease APOBEC3G level. Ref.9

Mutagenesis

T → E: Complete loss of viral infectivity in non permissive cells; no effect on the ability to decrease APOBEC3G level. Ref.9

Mutagenesis

114

C → S: Reduces the ability to decrease APOBEC3G level; when associated with S-133. Ref.11

Mutagenesis

133

C → S: Reduces the ability to decrease APOBEC3G level; when associated with S-114. Ref.11

Mutagenesis

144

S → A: 90% loss of viral infectivity in non permissive cells; no effect on the ability to decrease APOBEC3G level. Ref.5

Mutagenesis

157 – 160

KKIK → AAIA: 75% loss of membrane binding; decrease Pr55Gag binding. Ref.3

Mutagenesis

173 – 179

RWNKPQK → AWNAPQA: 40% loss of membrane binding; decrease Pr55Gag binding.

Mutagenesis

179 – 184

KTKGHR → ATAGHA: 25% loss of membrane binding; decrease Pr55Gag binding.

Mutagenesis

188

T → A: No effect on the ability to decrease APOBEC3G level. Ref.11

Sequences

Sequence

Length

Mass (Da)

Tools

P69723 [UniParc].

Last modified August 13, 1987. Version 1.
Checksum: D22589F3955CBE40
Show »

FASTA

192

22,513

        10         20         30         40         50         60 
MENRWQVMIV WQVDRMRIRT WKSLVKHHMY VSGKARGWFY RHHYESPHPR ISSEVHIPLG 

        70         80         90        100        110        120 
DARLVITTYW GLHTGERDWH LGQGVSIEWR KKRYSTQVDP ELADQLIHLY YFDCFSDSAI 

       130        140        150        160        170        180 
RKALLGHIVS PRCEYQAGHN KVGSLQYLAL AALITPKKIK PPLPSVTKLT EDRWNKPQKT 

       190 
KGHRGSHTMN GH

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References

[1]	"Complete nucleotide sequences of functional clones of the AIDS virus." Ratner L., Fisher A., Jagodzinski L.L., Mitsuya H., Liou R.-S., Gallo R.C., Wong-Staal F. AIDS Res. Hum. Retroviruses 3:57-69(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Subcellular localization of the Vif protein of human immunodeficiency virus type 1." Goncalves J., Jallepalli P., Gabuzda D.H. J. Virol. 68:704-712(1994) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[3]	"Biological activity of human immunodeficiency virus type 1 Vif requires membrane targeting by C-terminal basic domains." Goncalves J., Shi B., Yang X., Gabuzda D. J. Virol. 69:7196-7204(1995) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF 157-LYS--LYS-160 AND 173-ARG--ARG-184.
[4]	"Cytoskeleton association and virion incorporation of the human immunodeficiency virus type 1 Vif protein." Karczewski M.K., Strebel K. J. Virol. 70:494-507(1996) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[5]	"Phosphorylation of Vif and its role in HIV-1 replication." Yang X., Goncalves J., Gabuzda D. J. Biol. Chem. 271:10121-10129(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, MUTAGENESIS OF SER-144.
[6]	"Role of Vif in human immunodeficiency virus type 1 reverse transcription." Goncalves J., Korin Y., Zack J., Gabuzda D. J. Virol. 70:8701-8709(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Characterization of human immunodeficiency virus type 1 Vif particle incorporation." Camaur D., Trono D. J. Virol. 70:6106-6111(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INCORPORATION IN THE VIRION.
[8]	"Human immunodeficiency virus type 1 Vif protein binds to the Pr55Gag precursor." Bouyac M., Courcoul M., Bertoia G., Baudat Y., Gabuzda D., Blanc D., Chazal N., Boulanger P., Sire J., Vigne R., Spire B. J. Virol. 71:9358-9365(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PR55GAG.
[9]	"Mitogen-activated protein kinase phosphorylates and regulates the HIV-1 Vif protein." Yang X., Gabuzda D. J. Biol. Chem. 273:29879-29887(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY MAP4K1, PROTEIN SEQUENCE OF 159-164 AND 94-98, MUTAGENESIS OF THR-96.
[10]	"Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex." Yu X., Yu Y., Liu B., Luo K., Kong W., Mao P., Yu X.F. Science 302:1056-1060(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"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: FUNCTION, MUTAGENESIS OF CYS-114; CYS-133 AND THR-188.
[12]	"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.
[13]	"The tyrosine kinases Fyn and Hck favor the recruitment of tyrosine-phosphorylated APOBEC3G into vif-defective HIV-1 particles." Douaisi M., Dussart S., Courcoul M., Bessou G., Lerner E.C., Decroly E., Vigne R. Biochem. Biophys. Res. Commun. 329:917-924(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HOST HCK AND FYN.
[14]	"Identification of two distinct human immunodeficiency virus type 1 Vif determinants critical for interactions with human APOBEC3G and APOBEC3F." Russell R.A., Pathak V.K. J. Virol. 81:8201-8210(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HOST APOBEC3F AND APOBEC3G.
[15]	"The Vif accessory protein alters the cell cycle of human immunodeficiency virus type 1 infected cells." Wang J., Shackelford J.M., Casella C.R., Shivers D.K., Rapaport E.L., Liu B., Yu X.F., Finkel T.H. Virology 359:243-252(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL CYCLE ARREST.
[16]	"Characterization of conserved motifs in HIV-1 Vif required for APOBEC3G and APOBEC3F interaction." He Z., Zhang W., Chen G., Xu R., Yu X.F. J. Mol. Biol. 381:1000-1011(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HOST APOBEC3F AND APOBEC3G.
[17]	"MDM2 is a novel E3 ligase for HIV-1 Vif." Izumi T., Takaori-Kondo A., Shirakawa K., Higashitsuji H., Itoh K., Io K., Matsui M., Iwai K., Kondoh H., Sato T., Tomonaga M., Ikeda S., Akari H., Koyanagi Y., Fujita J., Uchiyama T. Retrovirology 6:1-1(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HOST MDM2.
[18]	"Mutational analysis of the HIV-1 auxiliary protein Vif identifies independent domains important for the physical and functional interaction with HIV-1 reverse transcriptase." Kataropoulou A., Bovolenta C., Belfiore A., Trabatti S., Garbelli A., Porcellini S., Lupo R., Maga G. Nucleic Acids Res. 37:3660-3669(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH THE REVERSE TRANSCRIPTASE.
[19]	"HIV-1 Vif binds to APOBEC3G mRNA and inhibits its translation." Mercenne G., Bernacchi S., Richer D., Bec G., Henriet S., Paillart J.C., Marquet R. Nucleic Acids Res. 38:633-646(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Web resources

BioAfrica HIV proteomics resource

Vif entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	K03455 Genomic RNA. Translation: AAB50260.1.
RefSeq	NP_057851.1. NC_001802.1.
3D structure databases
ProteinModelPortal	P69723.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	155459.
Enzyme and pathway databases
Reactome	REACT_116125. Disease.
Family and domain databases
InterPro	IPR000475. Viral_infect. [Graphical view]
Pfam	PF00559. Vif. 1 hit. [Graphical view]
PRINTS	PR00349. VIRIONINFFCT.
ProtoNet	Search...

Entry information

Entry name

VIF_HV1H2

Accession

Primary (citable) accession number: P69723
Secondary accession number(s): P03401

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	August 13, 1987
Last modified:	April 3, 2013
This is version 62 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Cleaved into the following 2 chains:

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protocols and materials databases

Genome annotation databases

Enzyme and pathway databases

Family and domain databases

Entry information

Relevant documents