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 13-FEB-2019, entry version 97. 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; 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., RA Gallo R.C., Wong-Staal F.; RT "Complete nucleotide sequences of functional clones of the AIDS RT virus."; RL AIDS Res. Hum. Retroviruses 3:57-69(1987). RN [2] RP SUBCELLULAR LOCATION. RX PubMed=8289374; 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; RA Goncalves J., Shi B., Yang X., Gabuzda D.; RT "Biological activity of human immunodeficiency virus type 1 Vif RT requires membrane targeting by C-terminal basic domains."; RL J. Virol. 69:7196-7204(1995). RN [4] RP SUBCELLULAR LOCATION. RX PubMed=8523563; 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; 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; 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; 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 RT HIV-1 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- RT Cul5-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 RT its 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., RA Decroly E., 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 RT Vif determinants critical for interactions with human APOBEC3G and RT 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 RT immunodeficiency 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 RT APOBEC3G 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., RA Io K., Matsui M., Iwai K., Kondoh H., Sato T., Tomonaga M., Ikeda S., RA Akari H., 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 RT interaction 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., RA Paillart J.C., 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 CC APOBEC3F and APOBEC3G. Forms a complex with host APOBEC3F and CC APOBEC3G thus preventing the entry of these lethally hypermutating CC enzymes into progeny virions. Recruits an active E3 ubiquitin CC ligase complex composed of elongin BC, CUL5, and RBX2 to induce CC polyubiquitination of APOBEC3G and APOBEC3F. In turn, they are CC directed to the 26S proteasome for degradation. Vif interaction CC with APOBEC3G also blocks its cytidine deaminase activity in a CC proteasome-independent manner, suggesting a dual inhibitory CC mechanism. May interact directly with APOBEC3G mRNA in order to CC inhibit its translation. Seems to play a role in viral morphology CC by affecting the stability of the viral nucleoprotein core. CC Finally, Vif also contributes to the G2 cell cycle arrest observed CC in 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 CC with viral RNA and Pr55Gag precursor; these interactions mediate CC Vif incorporation into the virion. Interacts with the viral CC reverse transcriptase. Interacts with human APOBEC3F and APOBEC3G. CC Interacts with host UBCE7IP1 isoform 3/ZIN and possibly with SAT. CC Interacts with host tyrosine kinases HCK and FYN; these CC interactions may decrease level of phosphorylated APOBEC3G CC incorporation into virions. Interacts with host ABCE1; this CC interaction may play a role in protecting viral RNA from damage CC during viral assembly. Forms an E3 ligase complex by interacting CC with host CUL5 and elongin BC complex (ELOB and ELOC). Interacts CC with host MDM2; this interaction targets Vif for degradation by CC 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 Self; NbExp=4; IntAct=EBI-15528966, EBI-15528966; CC Q9HC16:APOBEC3G (xeno); NbExp=3; IntAct=EBI-15528966, EBI-717839; CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000255|HAMAP- CC Rule:MF_04081}. Host cell membrane {ECO:0000255|HAMAP- CC Rule:MF_04081}; Peripheral membrane protein {ECO:0000255|HAMAP- CC Rule:MF_04081}; Cytoplasmic side {ECO:0000255|HAMAP- CC Rule:MF_04081}. Virion {ECO:0000255|HAMAP-Rule:MF_04081}. Note=In CC the cytoplasm, seems to colocalize with intermediate filament CC vimentin. A fraction is associated with the cytoplasmic side of CC cellular membranes, presumably via the interaction with Pr55Gag CC precursor. Incorporated in virions at a ratio of approximately 7 CC to 20 molecules per virion. {ECO:0000255|HAMAP-Rule:MF_04081}. CC -!- INDUCTION: Expressed late during infection in a Rev-dependent CC manner. {ECO:0000255|HAMAP-Rule:MF_04081}. CC -!- DOMAIN: The BC-like-box motif mediates the interaction with CC elongin BC 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 CC by stress and mitogens, these phosphorylations could be involved CC in this process. Ser-144 phosphorylation may inhibit elongin BC CC complex binding. {ECO:0000255|HAMAP-Rule:MF_04081, CC ECO:0000269|PubMed:8626571, ECO:0000269|PubMed:9792705}. CC -!- PTM: Processed in virion by the viral protease. CC {ECO:0000255|HAMAP-Rule:MF_04081}. CC -!- PTM: Polyubiquitinated and degraded by the proteasome in the CC presence 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 CC initiate a DNA base repair pathway and compromise the structural CC integrity of the ssDNA. In the absence of Vif, the virion is CC morphologically abnormal. {ECO:0000255|HAMAP-Rule:MF_04081}. CC -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M CC (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). CC The vast majority of strains found worldwide belong to the group CC M. Group O seems to be endemic to and largely confined to Cameroon CC and neighboring countries in West Central Africa, where these CC viruses represent a small minority of HIV-1 strains. The group N CC is represented by a limited number of isolates from Cameroonian CC persons. The group M is further subdivided in 9 clades or subtypes CC (A to D, F to H, J and K). {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, CC but is dispensable for replication in 'permissive' cell lines, CC such as 293T cells. In nonpermissive cells, Vif-defective viruses CC can produce virions, but they fail to complete reverse CC transcription and cannot successfully infect new cells. CC {ECO:0000255|HAMAP-Rule:MF_04081}. CC -!- SIMILARITY: Belongs to the primate lentivirus group Vif protein CC family. {ECO:0000255|HAMAP-Rule:MF_04081, ECO:0000305}. CC -!- WEB RESOURCE: Name=BioAfrica HIV proteomics resource; Note=Vif CC entry; CC URL="http://www.bioafrica.net/proteomics/VIFprot.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; K03455; AAB50260.1; -; Genomic_RNA. DR RefSeq; NP_057851.1; NC_001802.1. DR DisProt; DP00875; -. DR ProteinModelPortal; P69723; -. DR SMR; P69723; -. DR BioGrid; 1205539; 62. DR DIP; DIP-61318N; -. DR IntAct; P69723; 5. DR iPTMnet; P69723; -. DR PRIDE; P69723; -. DR GeneID; 155459; -. DR KEGG; vg:155459; -. DR KO; K22892; -. 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:0019012; C:virion; IEA:UniProtKB-SubCell. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-UniRule. DR GO; GO:0030260; P:entry into host cell; TAS:Reactome. DR GO; GO:0075713; P:establishment of integrated proviral latency; TAS:Reactome. DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; TAS:Reactome. DR GO; GO:0051169; P:nuclear transport; TAS:Reactome. DR GO; GO:0006278; P:RNA-dependent DNA biosynthetic process; TAS:Reactome. DR GO; GO:0019061; P:uncoating of virus; TAS:Reactome. DR GO; GO:0019058; P:viral life cycle; TAS:Reactome. DR GO; GO:0019068; P:virion assembly; TAS:Reactome. DR HAMAP; MF_04081; HIV_VIF; 1. DR InterPro; IPR000475; Viral_infect. DR Pfam; PF00559; Vif; 1. DR PRINTS; PR00349; VIRIONINFFCT. PE 1: Evidence at protein level; KW AIDS; Complete proteome; Direct protein sequencing; KW Host cell membrane; Host cytoplasm; Host membrane; KW Host-virus interaction; Membrane; Phosphoprotein; Reference proteome; KW RNA-binding; Ubl conjugation; Ubl conjugation pathway; Virion. FT CHAIN 1 192 Virion infectivity factor. FT {ECO:0000255|HAMAP-Rule:MF_04081}. FT /FTId=PRO_0000042759. FT CHAIN 1 150 p17. {ECO:0000255|HAMAP-Rule:MF_04081}. FT /FTId=PRO_0000042760. FT CHAIN 151 192 p7. {ECO:0000255|HAMAP-Rule:MF_04081}. FT /FTId=PRO_0000042761. FT REGION 14 17 Interaction with host APOBEC3F; F1-box. FT {ECO:0000255|HAMAP-Rule:MF_04081}. FT REGION 40 44 Interaction with host APOBEC3G; G-box. FT {ECO:0000255|HAMAP-Rule:MF_04081}. FT REGION 54 72 Interaction with host APOBEC3F and FT APOBEC3G; FG-box. {ECO:0000255|HAMAP- FT Rule:MF_04081}. FT REGION 74 79 Interaction with host APOBEC3F; F2-box. FT {ECO:0000255|HAMAP-Rule:MF_04081}. FT REGION 75 114 RNA-binding. {ECO:0000255|HAMAP- FT Rule:MF_04081}. FT REGION 151 164 Multimerization. {ECO:0000255|HAMAP- FT Rule:MF_04081}. FT REGION 171 172 Membrane association. {ECO:0000255|HAMAP- FT Rule:MF_04081}. FT MOTIF 108 139 HCCH motif. {ECO:0000255|HAMAP- FT Rule:MF_04081}. FT MOTIF 144 153 BC-box-like motif. {ECO:0000255|HAMAP- FT Rule:MF_04081}. FT SITE 150 151 Cleavage in virion (by viral protease). FT {ECO:0000255|HAMAP-Rule:MF_04081}. FT MOD_RES 96 96 Phosphothreonine; by host MAP4K1. FT {ECO:0000255|HAMAP-Rule:MF_04081, FT ECO:0000269|PubMed:9792705}. FT MOD_RES 144 144 Phosphoserine; by host. FT {ECO:0000255|HAMAP-Rule:MF_04081, FT ECO:0000269|PubMed:8626571}. FT MOD_RES 155 155 Phosphothreonine; by host. FT {ECO:0000255|HAMAP-Rule:MF_04081, FT ECO:0000269|PubMed:8626571}. FT MOD_RES 165 165 Phosphoserine; by host MAP4K1. FT {ECO:0000255|HAMAP-Rule:MF_04081, FT ECO:0000269|PubMed:9792705}. FT MOD_RES 188 188 Phosphothreonine; by host. FT {ECO:0000255|HAMAP-Rule:MF_04081, FT ECO:0000269|PubMed:8626571}. FT MUTAGEN 96 96 T->A: 90% loss of reverse transcriptase FT activity in virions; no effect on the FT ability to decrease APOBEC3G level. FT {ECO:0000269|PubMed:9792705}. FT MUTAGEN 96 96 T->E: Complete loss of viral infectivity FT in non permissive cells; no effect on the FT ability to decrease APOBEC3G level. FT {ECO:0000269|PubMed:9792705}. FT MUTAGEN 114 114 C->S: Reduces the ability to decrease FT APOBEC3G level; when associated with S- FT 133. {ECO:0000269|PubMed:14672928}. FT MUTAGEN 133 133 C->S: Reduces the ability to decrease FT APOBEC3G level; when associated with S- FT 114. {ECO:0000269|PubMed:14672928}. FT MUTAGEN 144 144 S->A: 90% loss of viral infectivity in FT non permissive cells; no effect on the FT ability to decrease APOBEC3G level. FT {ECO:0000269|PubMed:8626571}. FT MUTAGEN 157 160 KKIK->AAIA: 75% loss of membrane binding; FT decrease Pr55Gag binding. FT {ECO:0000269|PubMed:7474141}. FT MUTAGEN 173 179 RWNKPQK->AWNAPQA: 40% loss of membrane FT binding; decrease Pr55Gag binding. FT MUTAGEN 179 184 KTKGHR->ATAGHA: 25% loss of membrane FT binding; decrease Pr55Gag binding. FT MUTAGEN 188 188 T->A: No effect on the ability to FT decrease APOBEC3G level. FT {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 //