VIF_HV1H2
ID VIF_HV1H2 Reviewed; 192 AA.
AC P69723; P03401;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Virion infectivity factor {ECO:0000255|HAMAP-Rule:MF_04081};
DE Short=Vif {ECO:0000255|HAMAP-Rule:MF_04081};
DE AltName: Full=SOR protein {ECO:0000255|HAMAP-Rule:MF_04081};
DE Contains:
DE RecName: Full=p17 {ECO:0000255|HAMAP-Rule:MF_04081};
DE Contains:
DE RecName: Full=p7 {ECO:0000255|HAMAP-Rule:MF_04081};
GN Name=vif {ECO:0000255|HAMAP-Rule:MF_04081};
OS Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)
OS (HIV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11706;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=3040055; DOI=10.1089/aid.1987.3.57;
RA Ratner L., Fisher A., Jagodzinski L.L., Mitsuya H., Liou R.-S., Gallo R.C.,
RA Wong-Staal F.;
RT "Complete nucleotide sequences of functional clones of the AIDS virus.";
RL AIDS Res. Hum. Retroviruses 3:57-69(1987).
RN [2]
RP SUBCELLULAR LOCATION.
RX PubMed=8289374; DOI=10.1128/jvi.68.2.704-712.1994;
RA Goncalves J., Jallepalli P., Gabuzda D.H.;
RT "Subcellular localization of the Vif protein of human immunodeficiency
RT virus type 1.";
RL J. Virol. 68:704-712(1994).
RN [3]
RP MUTAGENESIS OF 157-LYS--LYS-160 AND 173-ARG--ARG-184.
RX PubMed=7474141; DOI=10.1128/jvi.69.11.7196-7204.1995;
RA Goncalves J., Shi B., Yang X., Gabuzda D.;
RT "Biological activity of human immunodeficiency virus type 1 Vif requires
RT membrane targeting by C-terminal basic domains.";
RL J. Virol. 69:7196-7204(1995).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=8523563; DOI=10.1128/jvi.70.1.494-507.1996;
RA Karczewski M.K., Strebel K.;
RT "Cytoskeleton association and virion incorporation of the human
RT immunodeficiency virus type 1 Vif protein.";
RL J. Virol. 70:494-507(1996).
RN [5]
RP PHOSPHORYLATION AT SER-144; THR-155 AND THR-188, AND MUTAGENESIS OF
RP SER-144.
RX PubMed=8626571; DOI=10.1074/jbc.271.17.10121;
RA Yang X., Goncalves J., Gabuzda D.;
RT "Phosphorylation of Vif and its role in HIV-1 replication.";
RL J. Biol. Chem. 271:10121-10129(1996).
RN [6]
RP FUNCTION.
RX PubMed=8970997; DOI=10.1128/jvi.70.12.8701-8709.1996;
RA Goncalves J., Korin Y., Zack J., Gabuzda D.;
RT "Role of Vif in human immunodeficiency virus type 1 reverse
RT transcription.";
RL J. Virol. 70:8701-8709(1996).
RN [7]
RP INCORPORATION IN THE VIRION.
RX PubMed=8709234; DOI=10.1128/jvi.70.9.6106-6111.1996;
RA Camaur D., Trono D.;
RT "Characterization of human immunodeficiency virus type 1 Vif particle
RT incorporation.";
RL J. Virol. 70:6106-6111(1996).
RN [8]
RP INTERACTION WITH PR55GAG.
RX PubMed=9371595; DOI=10.1128/jvi.71.12.9358-9365.1997;
RA Bouyac M., Courcoul M., Bertoia G., Baudat Y., Gabuzda D., Blanc D.,
RA Chazal N., Boulanger P., Sire J., Vigne R., Spire B.;
RT "Human immunodeficiency virus type 1 Vif protein binds to the Pr55Gag
RT precursor.";
RL J. Virol. 71:9358-9365(1997).
RN [9]
RP PHOSPHORYLATION AT THR-96 AND SER-165 BY MAP4K1, PROTEIN SEQUENCE OF
RP 159-164 AND 94-98, AND MUTAGENESIS OF THR-96.
RX PubMed=9792705; DOI=10.1074/jbc.273.45.29879;
RA Yang X., Gabuzda D.;
RT "Mitogen-activated protein kinase phosphorylates and regulates the HIV-1
RT Vif protein.";
RL J. Biol. Chem. 273:29879-29887(1998).
RN [10]
RP FUNCTION.
RX PubMed=14564014; DOI=10.1126/science.1089591;
RA Yu X., Yu Y., Liu B., Luo K., Kong W., Mao P., Yu X.F.;
RT "Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-
RT SCF complex.";
RL Science 302:1056-1060(2003).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF CYS-114; CYS-133 AND THR-188.
RX PubMed=14672928; DOI=10.1074/jbc.m313093200;
RA Mehle A., Strack B., Ancuta P., Zhang C., McPike M., Gabuzda D.;
RT "Vif overcomes the innate antiviral activity of APOBEC3G by promoting its
RT degradation in the ubiquitin-proteasome pathway.";
RL J. Biol. Chem. 279:7792-7798(2004).
RN [12]
RP REVIEW.
RX PubMed=15177194; DOI=10.1016/j.molmed.2004.04.008;
RA Rose K.M., Marin M., Kozak S.L., Kabat D.;
RT "The viral infectivity factor (Vif) of HIV-1 unveiled.";
RL Trends Mol. Med. 10:291-297(2004).
RN [13]
RP INTERACTION WITH HOST HCK AND FYN.
RX PubMed=15752743; DOI=10.1016/j.bbrc.2005.02.057;
RA Douaisi M., Dussart S., Courcoul M., Bessou G., Lerner E.C., Decroly E.,
RA Vigne R.;
RT "The tyrosine kinases Fyn and Hck favor the recruitment of tyrosine-
RT phosphorylated APOBEC3G into vif-defective HIV-1 particles.";
RL Biochem. Biophys. Res. Commun. 329:917-924(2005).
RN [14]
RP INTERACTION WITH HOST APOBEC3F AND APOBEC3G.
RX PubMed=17522216; DOI=10.1128/jvi.00395-07;
RA Russell R.A., Pathak V.K.;
RT "Identification of two distinct human immunodeficiency virus type 1 Vif
RT determinants critical for interactions with human APOBEC3G and APOBEC3F.";
RL J. Virol. 81:8201-8210(2007).
RN [15]
RP FUNCTION IN CELL CYCLE ARREST.
RX PubMed=17056089; DOI=10.1016/j.virol.2006.09.026;
RA Wang J., Shackelford J.M., Casella C.R., Shivers D.K., Rapaport E.L.,
RA Liu B., Yu X.F., Finkel T.H.;
RT "The Vif accessory protein alters the cell cycle of human immunodeficiency
RT virus type 1 infected cells.";
RL Virology 359:243-252(2007).
RN [16]
RP INTERACTION WITH HOST APOBEC3F AND APOBEC3G.
RX PubMed=18619467; DOI=10.1016/j.jmb.2008.06.061;
RA He Z., Zhang W., Chen G., Xu R., Yu X.F.;
RT "Characterization of conserved motifs in HIV-1 Vif required for APOBEC3G
RT and APOBEC3F interaction.";
RL J. Mol. Biol. 381:1000-1011(2008).
RN [17]
RP INTERACTION WITH HOST MDM2.
RX PubMed=19128510; DOI=10.1186/1742-4690-6-1;
RA Izumi T., Takaori-Kondo A., Shirakawa K., Higashitsuji H., Itoh K., Io K.,
RA Matsui M., Iwai K., Kondoh H., Sato T., Tomonaga M., Ikeda S., Akari H.,
RA Koyanagi Y., Fujita J., Uchiyama T.;
RT "MDM2 is a novel E3 ligase for HIV-1 Vif.";
RL Retrovirology 6:1-1(2009).
RN [18]
RP INTERACTION WITH THE REVERSE TRANSCRIPTASE.
RX PubMed=19369217; DOI=10.1093/nar/gkp226;
RA Kataropoulou A., Bovolenta C., Belfiore A., Trabatti S., Garbelli A.,
RA Porcellini S., Lupo R., Maga G.;
RT "Mutational analysis of the HIV-1 auxiliary protein Vif identifies
RT independent domains important for the physical and functional interaction
RT with HIV-1 reverse transcriptase.";
RL Nucleic Acids Res. 37:3660-3669(2009).
RN [19]
RP FUNCTION.
RX PubMed=19910370; DOI=10.1093/nar/gkp1009;
RA Mercenne G., Bernacchi S., Richer D., Bec G., Henriet S., Paillart J.C.,
RA Marquet R.;
RT "HIV-1 Vif binds to APOBEC3G mRNA and inhibits its translation.";
RL Nucleic Acids Res. 38:633-646(2010).
CC -!- FUNCTION: Counteracts the innate antiviral activity of host APOBEC3F
CC and APOBEC3G. Forms a complex with host APOBEC3F and APOBEC3G thus
CC preventing the entry of these lethally hypermutating enzymes into
CC progeny virions. Recruits an active E3 ubiquitin ligase complex
CC composed of elongin BC, CUL5, and RBX2 to induce polyubiquitination of
CC APOBEC3G and APOBEC3F. In turn, they are directed to the 26S proteasome
CC for degradation. Vif interaction with APOBEC3G also blocks its cytidine
CC deaminase activity in a proteasome-independent manner, suggesting a
CC dual inhibitory mechanism. May interact directly with APOBEC3G mRNA in
CC order to inhibit its translation. Seems to play a role in viral
CC morphology by affecting the stability of the viral nucleoprotein core.
CC Finally, Vif also contributes to the G2 cell cycle arrest observed in
CC HIV infected cells. {ECO:0000255|HAMAP-Rule:MF_04081,
CC ECO:0000269|PubMed:14564014, ECO:0000269|PubMed:14672928,
CC ECO:0000269|PubMed:17056089, ECO:0000269|PubMed:19910370,
CC ECO:0000269|PubMed:8970997}.
CC -!- SUBUNIT: Homomultimer; in vitro and presumably in vivo. Interacts with
CC viral RNA and Pr55Gag precursor; these interactions mediate Vif
CC incorporation into the virion. Interacts with the viral reverse
CC transcriptase. Interacts with human APOBEC3F and APOBEC3G. Interacts
CC with host UBCE7IP1 isoform 3/ZIN and possibly with SAT. Interacts with
CC host tyrosine kinases HCK and FYN; these interactions may decrease
CC level of phosphorylated APOBEC3G incorporation into virions. Interacts
CC with host ABCE1; this interaction may play a role in protecting viral
CC RNA from damage during viral assembly. Forms an E3 ligase complex by
CC interacting with host CUL5 and elongin BC complex (ELOB and ELOC).
CC Interacts with host MDM2; this interaction targets Vif for degradation
CC by the proteasome. {ECO:0000255|HAMAP-Rule:MF_04081,
CC ECO:0000269|PubMed:15752743, ECO:0000269|PubMed:17522216,
CC ECO:0000269|PubMed:18619467, ECO:0000269|PubMed:19128510,
CC ECO:0000269|PubMed:19369217, ECO:0000269|PubMed:9371595}.
CC -!- INTERACTION:
CC P69723; P69723: vif; NbExp=4; IntAct=EBI-15528966, EBI-15528966;
CC P69723; Q9HC16: APOBEC3G; Xeno; NbExp=3; IntAct=EBI-15528966, EBI-717839;
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04081}.
CC Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04081}; Peripheral
CC membrane protein {ECO:0000255|HAMAP-Rule:MF_04081}; Cytoplasmic side
CC {ECO:0000255|HAMAP-Rule:MF_04081}. Virion {ECO:0000255|HAMAP-
CC Rule:MF_04081}. Note=In the cytoplasm, seems to colocalize with
CC intermediate filament vimentin. A fraction is associated with the
CC cytoplasmic side of cellular membranes, presumably via the interaction
CC with Pr55Gag precursor. Incorporated in virions at a ratio of
CC approximately 7 to 20 molecules per virion. {ECO:0000255|HAMAP-
CC Rule:MF_04081}.
CC -!- INDUCTION: Expressed late during infection in a Rev-dependent manner.
CC {ECO:0000255|HAMAP-Rule:MF_04081}.
CC -!- DOMAIN: The BC-like-box motif mediates the interaction with elongin BC
CC complex. {ECO:0000255|HAMAP-Rule:MF_04081}.
CC -!- DOMAIN: The HCCH motif (H-x(5)-C-x(18)-C-x(5)-H) mediates the
CC interaction with CUL5. {ECO:0000255|HAMAP-Rule:MF_04081}.
CC -!- PTM: Highly phosphorylated on serine and threonine residues (By
CC similarity). Thr-96 and Ser-165 are phosphorylated by the mitogen
CC activated kinase MAP4K1. As the HIV-1 replication can be activated by
CC stress and mitogens, these phosphorylations could be involved in this
CC process. Ser-144 phosphorylation may inhibit elongin BC complex
CC binding. {ECO:0000255|HAMAP-Rule:MF_04081, ECO:0000269|PubMed:8626571,
CC ECO:0000269|PubMed:9792705}.
CC -!- PTM: Processed in virion by the viral protease. {ECO:0000255|HAMAP-
CC Rule:MF_04081}.
CC -!- PTM: Polyubiquitinated and degraded by the proteasome in the presence
CC of APOBEC3G. {ECO:0000255|HAMAP-Rule:MF_04081}.
CC -!- MISCELLANEOUS: Vif-defective viruses show catastrophic failure in
CC reverse transcription due to APOBEC-induced mutations that initiate a
CC DNA base repair pathway and compromise the structural integrity of the
CC ssDNA. In the absence of Vif, the virion is morphologically abnormal.
CC {ECO:0000255|HAMAP-Rule:MF_04081}.
CC -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC majority of strains found worldwide belong to the group M. Group O
CC seems to be endemic to and largely confined to Cameroon and neighboring
CC countries in West Central Africa, where these viruses represent a small
CC minority of HIV-1 strains. The group N is represented by a limited
CC number of isolates from Cameroonian persons. The group M is further
CC subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC {ECO:0000255|HAMAP-Rule:MF_04081}.
CC -!- MISCELLANEOUS: Required for replication in 'nonpermissive' cells,
CC including primary T-cells, macrophages and certain T-cell lines, but is
CC dispensable for replication in 'permissive' cell lines, such as 293T
CC cells. In nonpermissive cells, Vif-defective viruses can produce
CC virions, but they fail to complete reverse transcription and cannot
CC successfully infect new cells. {ECO:0000255|HAMAP-Rule:MF_04081}.
CC -!- SIMILARITY: Belongs to the primate lentivirus group Vif protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04081, ECO:0000305}.
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DR EMBL; K03455; AAB50260.1; -; Genomic_RNA.
DR RefSeq; NP_057851.1; NC_001802.1.
DR SMR; P69723; -.
DR BioGRID; 1205539; 63.
DR DIP; DIP-61318N; -.
DR IntAct; P69723; 5.
DR iPTMnet; P69723; -.
DR GeneID; 155459; -.
DR KEGG; vg:155459; -.
DR Reactome; R-HSA-162585; Uncoating of the HIV Virion.
DR Reactome; R-HSA-162588; Budding and maturation of HIV virion.
DR Reactome; R-HSA-162592; Integration of provirus.
DR Reactome; R-HSA-162594; Early Phase of HIV Life Cycle.
DR Reactome; R-HSA-164516; Minus-strand DNA synthesis.
DR Reactome; R-HSA-164525; Plus-strand DNA synthesis.
DR Reactome; R-HSA-164843; 2-LTR circle formation.
DR Reactome; R-HSA-173107; Binding and entry of HIV virion.
DR Reactome; R-HSA-175474; Assembly Of The HIV Virion.
DR Reactome; R-HSA-175567; Integration of viral DNA into host genomic DNA.
DR Reactome; R-HSA-177539; Autointegration results in viral DNA circles.
DR Reactome; R-HSA-180585; Vif-mediated degradation of APOBEC3G.
DR Reactome; R-HSA-180689; APOBEC3G mediated resistance to HIV-1 infection.
DR Reactome; R-HSA-180910; Vpr-mediated nuclear import of PICs.
DR PRO; PR:P69723; -.
DR Proteomes; UP000002241; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0044423; C:virion component; IEA:UniProtKB-UniRule.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0019058; P:viral life cycle; IEA:InterPro.
DR DisProt; DP00875; -.
DR HAMAP; MF_04081; HIV_VIF; 1.
DR InterPro; IPR000475; Vif.
DR Pfam; PF00559; Vif; 1.
DR PRINTS; PR00349; VIRIONINFFCT.
PE 1: Evidence at protein level;
KW AIDS; Direct protein sequencing; Host cell membrane; Host cytoplasm;
KW Host membrane; Host-virus interaction; Membrane; Phosphoprotein;
KW Reference proteome; RNA-binding; Ubl conjugation; Ubl conjugation pathway;
KW Virion.
FT CHAIN 1..192
FT /note="Virion infectivity factor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081"
FT /id="PRO_0000042759"
FT CHAIN 1..150
FT /note="p17"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081"
FT /id="PRO_0000042760"
FT CHAIN 151..192
FT /note="p7"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081"
FT /id="PRO_0000042761"
FT REGION 14..17
FT /note="Interaction with host APOBEC3F; F1-box"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081"
FT REGION 40..44
FT /note="Interaction with host APOBEC3G; G-box"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081"
FT REGION 54..72
FT /note="Interaction with host APOBEC3F and APOBEC3G; FG-box"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081"
FT REGION 74..79
FT /note="Interaction with host APOBEC3F; F2-box"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081"
FT REGION 75..114
FT /note="RNA-binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081"
FT REGION 151..164
FT /note="Multimerization"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081"
FT REGION 164..192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 171..172
FT /note="Membrane association"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081"
FT MOTIF 108..139
FT /note="HCCH motif"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081"
FT MOTIF 144..153
FT /note="BC-box-like motif"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081"
FT SITE 150..151
FT /note="Cleavage in virion (by viral protease)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081"
FT MOD_RES 96
FT /note="Phosphothreonine; by host MAP4K1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081,
FT ECO:0000269|PubMed:9792705"
FT MOD_RES 144
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081,
FT ECO:0000269|PubMed:8626571"
FT MOD_RES 155
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081,
FT ECO:0000269|PubMed:8626571"
FT MOD_RES 165
FT /note="Phosphoserine; by host MAP4K1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081,
FT ECO:0000269|PubMed:9792705"
FT MOD_RES 188
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04081,
FT ECO:0000269|PubMed:8626571"
FT MUTAGEN 96
FT /note="T->A: 90% loss of reverse transcriptase activity in
FT virions; no effect on the ability to decrease APOBEC3G
FT level."
FT /evidence="ECO:0000269|PubMed:9792705"
FT MUTAGEN 96
FT /note="T->E: Complete loss of viral infectivity in non
FT permissive cells; no effect on the ability to decrease
FT APOBEC3G level."
FT /evidence="ECO:0000269|PubMed:9792705"
FT MUTAGEN 114
FT /note="C->S: Reduces the ability to decrease APOBEC3G
FT level; when associated with S-133."
FT /evidence="ECO:0000269|PubMed:14672928"
FT MUTAGEN 133
FT /note="C->S: Reduces the ability to decrease APOBEC3G
FT level; when associated with S-114."
FT /evidence="ECO:0000269|PubMed:14672928"
FT MUTAGEN 144
FT /note="S->A: 90% loss of viral infectivity in non
FT permissive cells; no effect on the ability to decrease
FT APOBEC3G level."
FT /evidence="ECO:0000269|PubMed:8626571"
FT MUTAGEN 157..160
FT /note="KKIK->AAIA: 75% loss of membrane binding; decrease
FT Pr55Gag binding."
FT /evidence="ECO:0000269|PubMed:7474141"
FT MUTAGEN 173..179
FT /note="RWNKPQK->AWNAPQA: 40% loss of membrane binding;
FT decrease Pr55Gag binding."
FT MUTAGEN 179..184
FT /note="KTKGHR->ATAGHA: 25% loss of membrane binding;
FT decrease Pr55Gag binding."
FT MUTAGEN 188
FT /note="T->A: No effect on the ability to decrease APOBEC3G
FT level."
FT /evidence="ECO:0000269|PubMed:14672928"
SQ SEQUENCE 192 AA; 22513 MW; D22589F3955CBE40 CRC64;
MENRWQVMIV WQVDRMRIRT WKSLVKHHMY VSGKARGWFY RHHYESPHPR ISSEVHIPLG
DARLVITTYW GLHTGERDWH LGQGVSIEWR KKRYSTQVDP ELADQLIHLY YFDCFSDSAI
RKALLGHIVS PRCEYQAGHN KVGSLQYLAL AALITPKKIK PPLPSVTKLT EDRWNKPQKT
KGHRGSHTMN GH
