VPR_HV1BR
ID VPR_HV1BR Reviewed; 96 AA.
AC P05928;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Protein Vpr {ECO:0000255|HAMAP-Rule:MF_04080};
DE AltName: Full=R ORF protein {ECO:0000255|HAMAP-Rule:MF_04080};
DE AltName: Full=Viral protein R {ECO:0000255|HAMAP-Rule:MF_04080};
GN Name=vpr {ECO:0000255|HAMAP-Rule:MF_04080};
OS Human immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI)
OS (HIV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11686;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2981635; DOI=10.1016/0092-8674(85)90303-4;
RA Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M.;
RT "Nucleotide sequence of the AIDS virus, LAV.";
RL Cell 40:9-17(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Clone pNL4-3;
RA Buckler C.E., Buckler-White A.J., Willey R.L., McCoy J.;
RL Submitted (JUN-1988) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
RX PubMed=2136707;
RA Cohen E.A., Terwilliger E.F., Jalinoos Y., Proulx J., Sodroski J.G.,
RA Haseltine W.A.;
RT "Identification of HIV-1 vpr product and function.";
RL J. Acquir. Immune Defic. Syndr. 3:11-18(1990).
RN [4]
RP FUNCTION.
RX PubMed=2139896; DOI=10.1128/jvi.64.6.3097-3099.1990;
RA Cohen E.A., Dehni G., Sodroski J.G., Haseltine W.A.;
RT "Human immunodeficiency virus vpr product is a virion-associated regulatory
RT protein.";
RL J. Virol. 64:3097-3099(1990).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=8411357; DOI=10.1128/jvi.67.11.6542-6550.1993;
RA Lu Y.L., Spearman P., Ratner L.;
RT "Human immunodeficiency virus type 1 viral protein R localization in
RT infected cells and virions.";
RL J. Virol. 67:6542-6550(1993).
RN [6]
RP MUTAGENESIS OF ARG-32; ARG-62 AND CYS-76.
RX PubMed=8230445; DOI=10.1128/jvi.67.12.7229-7237.1993;
RA Paxton W., Connor R.I., Landau N.R.;
RT "Incorporation of Vpr into human immunodeficiency virus type 1 virions:
RT requirement for the p6 region of gag and mutational analysis.";
RL J. Virol. 67:7229-7237(1993).
RN [7]
RP FUNCTION.
RX PubMed=8041786; DOI=10.1073/pnas.91.15.7311;
RA Heinzinger N.K., Bukinsky M.I., Haggerty S.A., Ragland A.M.,
RA Kewalramani V., Lee M.A., Gendelman H.E., Ratner L., Stevenson M.,
RA Emerman M.;
RT "The Vpr protein of human immunodeficiency virus type 1 influences nuclear
RT localization of viral nucleic acids in nondividing host cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:7311-7315(1994).
RN [8]
RP INTERACTION WITH HUMAN SP1.
RX PubMed=7592727; DOI=10.1074/jbc.270.43.25564;
RA Wang L., Mukherjee S., Jia F., Narayan O., Zhao L.J.;
RT "Interaction of virion protein Vpr of human immunodeficiency virus type 1
RT with cellular transcription factor Sp1 and trans-activation of viral long
RT terminal repeat.";
RL J. Biol. Chem. 270:25564-25569(1995).
RN [9]
RP FUNCTION.
RX PubMed=7724608; DOI=10.1073/pnas.92.8.3621;
RA Refaeli Y., Levy D.N., Weiner D.B.;
RT "The glucocorticoid receptor type II complex is a target of the HIV-1 vpr
RT gene product.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:3621-3625(1995).
RN [10]
RP INTERACTION WITH P6-GAG.
RX PubMed=7474102; DOI=10.1128/jvi.69.11.6873-6879.1995;
RA Lu Y.L., Bennett R.P., Wills J.W., Gorelick R., Ratner L.;
RT "A leucine triplet repeat sequence (LXX)4 in p6gag is important for Vpr
RT incorporation into human immunodeficiency virus type 1 particles.";
RL J. Virol. 69:6873-6879(1995).
RN [11]
RP FUNCTION.
RX PubMed=7474100; DOI=10.1128/jvi.69.11.6859-6864.1995;
RA Re F., Braaten D., Franke E.K., Luban J.;
RT "Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by
RT inhibiting the activation of p34cdc2-cyclin B.";
RL J. Virol. 69:6859-6864(1995).
RN [12]
RP FUNCTION.
RX PubMed=7666531; DOI=10.1128/jvi.69.10.6304-6313.1995;
RA Jowett J.B., Planelles V., Poon B., Shah N.P., Chen M.L., Chen I.S.;
RT "The human immunodeficiency virus type 1 vpr gene arrests infected T cells
RT in the G2 + M phase of the cell cycle.";
RL J. Virol. 69:6304-6313(1995).
RN [13]
RP INTERACTION WITH HUMAN UNG.
RX PubMed=8551605; DOI=10.1128/jvi.70.2.697-704.1996;
RA Bouhamdan M., Benichou S., Rey F., Navarro J.-M., Agostini I., Spire B.,
RA Camonis J., Slupphaug G., Vigne R., Benarous R., Sire J.;
RT "Human immunodeficiency virus type 1 Vpr protein binds to the uracil DNA
RT glycosylase DNA repair enzyme.";
RL J. Virol. 70:697-704(1996).
RN [14]
RP INTERACTION WITH HUMAN TFIIB.
RX PubMed=8800208; DOI=10.1006/jmbi.1996.0485;
RA Agostini I., Navarro J.-M., Rey F., Bouhamdan M., Spire B., Vigne R.,
RA Sire J.;
RT "The human immunodeficiency virus type 1 Vpr transactivator: cooperation
RT with promoter-bound activator domains and binding to TFIIB.";
RL J. Mol. Biol. 261:599-606(1996).
RN [15]
RP MUTAGENESIS OF 80-ARG--ARG-90.
RX PubMed=9514978; DOI=10.1006/viro.1998.9028;
RA Zhou Y., Lu Y., Ratner L.;
RT "Arginine residues in the C-terminus of HIV-1 Vpr are important for nuclear
RT localization and cell cycle arrest.";
RL Virology 242:414-424(1998).
RN [16]
RP FUNCTION.
RX PubMed=9657723; DOI=10.1126/science.281.5374.266;
RA Poon B., Grovit-Ferbas K., Stewart S.A., Chen I.S.;
RT "Cell cycle arrest by Vpr in HIV-1 virions and insensitivity to
RT antiretroviral agents.";
RL Science 281:266-269(1998).
RN [17]
RP SUBCELLULAR LOCATION.
RX PubMed=9817747; DOI=10.1083/jcb.143.4.875;
RA Jenkins Y., McEntee M., Weis K., Greene W.C.;
RT "Characterization of HIV-1 vpr nuclear import: analysis of signals and
RT pathways.";
RL J. Cell Biol. 143:875-885(1998).
RN [18]
RP INTERACTION WITH HUMAN RAD23A.
RX PubMed=9371639; DOI=10.1128/jvi.71.12.9732-9742.1997;
RA Withers-Ward E.S., Jowett J.B., Stewart S.A., Xie Y.M., Garfinkel A.,
RA Shibagaki Y., Chow S.A., Shah N., Hanaoka F., Sawitz D.G., Armstrong R.W.,
RA Souza L.M., Chen I.S.;
RT "Human immunodeficiency virus type 1 Vpr interacts with HHR23A, a cellular
RT protein implicated in nucleotide excision DNA repair.";
RL J. Virol. 71:9732-9742(1997).
RN [19]
RP INTERACTION WITH HUMAN COPS6, AND MUTAGENESIS OF ALA-30; 20-LEU--LEU-26;
RP ALA-59; LEU-67; HIS-71; GLY-75 AND CYS-76.
RX PubMed=9520381; DOI=10.1073/pnas.95.7.3419;
RA Mahalingam S., Ayyavoo V., Patel M., Kieber-Emmons T., Kao G.D.,
RA Muschel R.J., Weiner D.B.;
RT "HIV-1 Vpr interacts with a human 34-kDa mov34 homologue, a cellular factor
RT linked to the G2/M phase transition of the mammalian cell cycle.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:3419-3424(1998).
RN [20]
RP INTERACTION WITH HUMAN KPNA1 AND KPNA2.
RX PubMed=9463369; DOI=10.1093/emboj/17.4.909;
RA Popov S., Rexach M., Zybarth G., Reiling N., Lee M.A., Ratner L.,
RA Lane C.M., Moore M.S., Blobel G., Bukrinsky M.;
RT "Viral protein R regulates nuclear import of the HIV-1 pre-integration
RT complex.";
RL EMBO J. 17:909-917(1998).
RN [21]
RP INTERACTION WITH HUMAN SP1.
RX PubMed=9685344; DOI=10.1074/jbc.273.32.20052;
RA Sawaya B.E., Khalili K., Mercer W.E., Denisova L., Amini S.;
RT "Cooperative actions of HIV-1 Vpr and p53 modulate viral gene
RT transcription.";
RL J. Biol. Chem. 273:20052-20057(1998).
RN [22]
RP MUTAGENESIS OF LEU-23; GLU-25; ALA-30; VAL-57; ARG-62; ILE-63;
RP 68-LEU--ILE-70 AND ARG-80.
RX PubMed=9837715; DOI=10.1006/jmbi.1998.2206;
RA Forget J., Yao X.J., Mercier J., Cohen E.A.;
RT "Human immunodeficiency virus type 1 vpr protein transactivation function:
RT mechanism and identification of domains involved.";
RL J. Mol. Biol. 284:915-923(1998).
RN [23]
RP FUNCTION.
RX PubMed=9539783; DOI=10.1073/pnas.95.8.4595;
RA Piller S.C., Jans P., Gage P.W., Jans D.A.;
RT "Extracellular HIV-1 virus protein R causes a large inward current and cell
RT death in cultured hippocampal neurons: implications for AIDS pathology.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:4595-4600(1998).
RN [24]
RP FUNCTION.
RX PubMed=9525900; DOI=10.1074/jbc.273.14.8009;
RA Bouhamdan M., Xue Y., Baudat Y., Hu B., Sire J., Pomerantz R.J., Duan L.X.;
RT "Diversity of HIV-1 Vpr interactions involves usage of the WXXF motif of
RT host cell proteins.";
RL J. Biol. Chem. 273:8009-8016(1998).
RN [25]
RP INTERACTION WITH HUMAN TFIIB.
RX PubMed=9874563; DOI=10.1084/jem.189.1.51;
RA Kino T., Gragerov A., Kopp J.B., Stauber R.H., Pavlakis G.N.,
RA Chrousos G.P.;
RT "The HIV-1 virion-associated protein vpr is a coactivator of the human
RT glucocorticoid receptor.";
RL J. Exp. Med. 189:51-62(1999).
RN [26]
RP MUTAGENESIS OF GLU-17; TRP-18; GLU-24; GLU-25; HIS-33; PHE-34; TRP-54;
RP HIS-71; HIS-78; SER-79; ARG-88; ALA-89 AND ARG-90.
RX PubMed=10074177; DOI=10.1128/jvi.73.4.3236-3245.1999;
RA Chen M., Elder R.T., Yu M., O'Gorman M.G., Selig L., Benarous R.,
RA Yamamoto A., Zhao Y.;
RT "Mutational analysis of Vpr-induced G2 arrest, nuclear localization, and
RT cell death in fission yeast.";
RL J. Virol. 73:3236-3245(1999).
RN [27]
RP MUTAGENESIS OF GLU-25; ALA-30; VAL-57 AND ARG-80.
RX PubMed=10359081; DOI=10.1016/s0014-5793(99)00501-3;
RA Agostini I., Navarro J.M., Bouhamdan M., Willetts K., Rey F., Spire B.,
RA Vigne R., Pomerantz R., Sire J.;
RT "The HIV-1 Vpr co-activator induces a conformational change in TFIIB.";
RL FEBS Lett. 450:235-239(1999).
RN [28]
RP FUNCTION.
RX PubMed=10518572; DOI=10.1073/pnas.96.21.12039;
RA Stewart S.A., Poon B., Jowett J.B., Xie Y., Chen I.S.;
RT "Lentiviral delivery of HIV-1 Vpr protein induces apoptosis in transformed
RT cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:12039-12043(1999).
RN [29]
RP MUTAGENESIS OF GLU-21; GLU-24; GLU-58 AND ARG-95.
RX PubMed=10196319; DOI=10.1128/jvi.73.5.4230-4238.1999;
RA Piller S.C., Ewart G.D., Jans D.A., Gage P.W., Cox G.B.;
RT "The amino-terminal region of Vpr from human immunodeficiency virus type 1
RT forms ion channels and kills neurons.";
RL J. Virol. 73:4230-4238(1999).
RN [30]
RP MUTAGENESIS OF ARG-73.
RX PubMed=10775627; DOI=10.1128/jvi.74.10.4877-4881.2000;
RA Sawaya B.E., Khalili K., Gordon J., Srinivasan A., Richardson M.,
RA Rappaport J., Amini S.;
RT "Transdominant activity of human immunodeficiency virus type 1 Vpr with a
RT mutation at residue R73.";
RL J. Virol. 74:4877-4881(2000).
RN [31]
RP FUNCTION.
RX PubMed=10620603; DOI=10.1084/jem.191.1.33;
RA Jacotot E., Ravagnan L., Loeffler M., Ferri K.F., Vieira H.L.A.,
RA Zamzami N., Costantini P., Druillennec S., Hoebeke J., Briand J.-P.,
RA Irinopoulou T., Daugas E., Susin S.A., Cointe D., Xie Z.H., Reed J.C.,
RA Roques B.P., Kroemer G.;
RT "The HIV-1 viral protein R induces apoptosis via a direct effect on the
RT mitochondrial permeability transition pore.";
RL J. Exp. Med. 191:33-46(2000).
RN [32]
RP PHOSPHORYLATION AT SER-79; SER-94 AND SER-96, AND MUTAGENESIS OF SER-79;
RP SER-94 AND SER-96.
RC STRAIN=Clone pNL4-3;
RX PubMed=10864665; DOI=10.1128/jvi.74.14.6520-6527.2000;
RA Zhou Y., Ratner L.;
RT "Phosphorylation of human immunodeficiency virus type 1 Vpr regulates cell
RT cycle arrest.";
RL J. Virol. 74:6520-6527(2000).
RN [33]
RP FUNCTION.
RX PubMed=10708425; DOI=10.1128/jvi.74.7.3105-3111.2000;
RA Stewart S.A., Poon B., Song J.Y., Chen I.S.;
RT "Human immunodeficiency virus type 1 vpr induces apoptosis through caspase
RT activation.";
RL J. Virol. 74:3105-3111(2000).
RN [34]
RP PHOSPHORYLATION AT SER-79.
RX PubMed=11860675; DOI=10.1089/088922202753472856;
RA Agostini I., Popov S., Hao T., Li J.H., Dubrovsky L., Chaika O., Chaika N.,
RA Lewis R., Bukrinsky M.;
RT "Phosphorylation of Vpr regulates HIV type 1 nuclear import and macrophage
RT infection.";
RL AIDS Res. Hum. Retroviruses 18:283-288(2002).
RN [35]
RP FUNCTION.
RX PubMed=12573582; DOI=10.1006/viro.2002.1777;
RA Chowdhury I.H., Wang X.F., Landau N.R., Robb M.L., Polonis V.R., Birx D.L.,
RA Kim J.H.;
RT "HIV-1 Vpr activates cell cycle inhibitor p21/Waf1/Cip1: a potential
RT mechanism of G2/M cell cycle arrest.";
RL Virology 305:371-377(2003).
RN [36]
RP FUNCTION.
RX PubMed=12634356; DOI=10.1128/jvi.77.7.3962-3972.2003;
RA Poon B., Chen I.S.;
RT "Human immunodeficiency virus type 1 (HIV-1) Vpr enhances expression from
RT unintegrated HIV-1 DNA.";
RL J. Virol. 77:3962-3972(2003).
RN [37]
RP INTERACTION WITH HUMAN CDC25C.
RX PubMed=14972559; DOI=10.1016/j.virol.2003.10.007;
RA Goh W.C., Manel N., Emerman M.;
RT "The human immunodeficiency virus Vpr protein binds Cdc25C: implications
RT for G2 arrest.";
RL Virology 318:337-349(2004).
RN [38]
RP INTERACTION WITH HUMAN SLC25A4; SLC25A5 AND SLC25A6.
RX PubMed=16120388; DOI=10.1016/j.mito.2004.06.012;
RA Deniaud A., Brenner C., Kroemer G.;
RT "Mitochondrial membrane permeabilization by HIV-1 Vpr.";
RL Mitochondrion 4:223-233(2004).
RN [39]
RP INTERACTION WITH ANKHD1.
RX PubMed=16098192; DOI=10.1111/j.1742-4658.2005.04821.x;
RA Miles M.C., Janket M.L., Wheeler E.D., Chattopadhyay A., Majumder B.,
RA Dericco J., Schafer E.A., Ayyavoo V.;
RT "Molecular and functional characterization of a novel splice variant of
RT ANKHD1 that lacks the KH domain and its role in cell survival and
RT apoptosis.";
RL FEBS J. 272:4091-4102(2005).
RN [40]
RP REVIEW.
RX PubMed=16511342;
RA Moon H.S., Yang J.S.;
RT "Role of HIV Vpr as a regulator of apoptosis and an effector on bystander
RT cells.";
RL Mol. Cells 21:7-20(2006).
RN [41]
RP INTERACTION WITH HUMAN SF3B2.
RX PubMed=16923959; DOI=10.1128/mcb.01170-06;
RA Terada Y., Yasuda Y.;
RT "Human immunodeficiency virus type 1 Vpr induces G2 checkpoint activation
RT by interacting with the splicing factor SAP145.";
RL Mol. Cell. Biol. 26:8149-8158(2006).
RN [42]
RP FUNCTION.
RX PubMed=17314515; DOI=10.4161/cc.6.2.3732;
RA Le Rouzic E., Belaiedouni N., Estrabaud E., Morel M., Rain J.-C.,
RA Transy C., Margottin-Goguet F.;
RT "HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor of
RT the Cul4-DDB1 ubiquitin ligase.";
RL Cell Cycle 6:182-188(2007).
RN [43]
RP FUNCTION.
RX PubMed=17630831; DOI=10.1371/journal.ppat.0030085;
RA Belzile J.P., Duisit G., Rougeau N., Mercier J., Finzi A., Cohen E.A.;
RT "HIV-1 Vpr-mediated G2 arrest involves the DDB1-CUL4A[VPRBP] E3 ubiquitin
RT ligase.";
RL PLoS Pathog. 3:E85-E85(2007).
RN [44]
RP INTERACTION WITH HOST DCAF1.
RX PubMed=23612978; DOI=10.1074/jbc.m112.416735;
RA Wang X., Singh S., Jung H.Y., Yang G., Jun S., Sastry K.J., Park J.I.;
RT "HIV-1 Vpr protein inhibits telomerase activity via the EDD-DDB1-VPRBP E3
RT ligase complex.";
RL J. Biol. Chem. 288:15474-15480(2013).
RN [45]
RP INTERACTION WITH HOST DCAF1.
RX PubMed=24116224; DOI=10.1371/journal.pone.0077320;
RA Maudet C., Sourisce A., Dragin L., Lahouassa H., Rain J.C., Bouaziz S.,
RA Ramirez B.C., Margottin-Goguet F.;
RT "HIV-1 Vpr Induces the Degradation of ZIP and sZIP, Adaptors of the NuRD
RT Chromatin Remodeling Complex, by Hijacking DCAF1/VprBP.";
RL PLoS ONE 8:E77320-E77320(2013).
CC -!- FUNCTION: During virus entry, plays a role in the transport of the
CC viral pre-integration (PIC) complex to the host nucleus. This function
CC is crucial for viral infection of non-dividing macrophages. May act
CC directly at the nuclear pore complex, by binding nucleoporins
CC phenylalanine-glycine (FG)-repeat regions. {ECO:0000255|HAMAP-
CC Rule:MF_04080, ECO:0000269|PubMed:10518572,
CC ECO:0000269|PubMed:10620603, ECO:0000269|PubMed:10708425,
CC ECO:0000269|PubMed:12573582, ECO:0000269|PubMed:12634356,
CC ECO:0000269|PubMed:17314515, ECO:0000269|PubMed:17630831,
CC ECO:0000269|PubMed:2136707, ECO:0000269|PubMed:2139896,
CC ECO:0000269|PubMed:7474100, ECO:0000269|PubMed:7666531,
CC ECO:0000269|PubMed:7724608, ECO:0000269|PubMed:8041786,
CC ECO:0000269|PubMed:9525900, ECO:0000269|PubMed:9539783,
CC ECO:0000269|PubMed:9657723}.
CC -!- FUNCTION: During virus replication, may deplete host UNG protein, and
CC incude G2-M cell cycle arrest. Acts by targeting specific host proteins
CC for degradation by the 26S proteasome, through association with the
CC cellular CUL4A-DDB1 E3 ligase complex by direct interaction with host
CC VPRPB/DCAF-1. Cell cycle arrest reportedly occurs within hours of
CC infection and is not blocked by antiviral agents, suggesting that it is
CC initiated by the VPR carried into the virion. Additionally, VPR induces
CC apoptosis in a cell cycle dependent manner suggesting that these two
CC effects are mechanistically linked. Detected in the serum and
CC cerebrospinal fluid of AIDS patient, VPR may also induce cell death to
CC bystander cells. {ECO:0000255|HAMAP-Rule:MF_04080}.
CC -!- SUBUNIT: Homooligomer, may form homodimer. Interacts with p6-gag region
CC of the Pr55 Gag precursor protein through a (Leu-X-X)4 motif near the
CC C-terminus of the P6gag protein. Interacts with host UNG. May interact
CC with host RAD23A/HHR23A. Interacts with host VPRBP/DCAF1, leading to
CC hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex, mediating
CC ubiquitination of host proteins such as TERT and ZGPAT and arrest of
CC the cell cycle in G2 phase. {ECO:0000255|HAMAP-Rule:MF_04080,
CC ECO:0000269|PubMed:14972559, ECO:0000269|PubMed:16098192,
CC ECO:0000269|PubMed:16120388, ECO:0000269|PubMed:16923959,
CC ECO:0000269|PubMed:23612978, ECO:0000269|PubMed:24116224,
CC ECO:0000269|PubMed:7474102, ECO:0000269|PubMed:7592727,
CC ECO:0000269|PubMed:8551605, ECO:0000269|PubMed:8800208,
CC ECO:0000269|PubMed:9371639, ECO:0000269|PubMed:9463369,
CC ECO:0000269|PubMed:9520381, ECO:0000269|PubMed:9685344,
CC ECO:0000269|PubMed:9874563}.
CC -!- INTERACTION:
CC P05928; Q9Y4B6-3: DCAF1; Xeno; NbExp=2; IntAct=EBI-9210238, EBI-9915372;
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000255|HAMAP-Rule:MF_04080}. Host
CC nucleus {ECO:0000255|HAMAP-Rule:MF_04080}. Host extracellular space
CC {ECO:0000255|HAMAP-Rule:MF_04080}. Note=Incorporation into virion is
CC dependent on p6 GAG sequences. Lacks a canonical nuclear localization
CC signal, thus import into nucleus may function independently of the
CC human importin pathway. Detected in high quantity in the serum and
CC cerebrospinal fluid of AIDS patient. {ECO:0000255|HAMAP-Rule:MF_04080}.
CC -!- PTM: Phosphorylated on several residues by host. These phosphorylations
CC regulate VPR activity for the nuclear import of the HIV-1 pre-
CC integration complex. {ECO:0000255|HAMAP-Rule:MF_04080,
CC ECO:0000269|PubMed:10864665, ECO:0000269|PubMed:11860675}.
CC -!- MISCELLANEOUS: The infectious clone pNL4-3 is a chimeric provirus that
CC consists of DNA from HIV isolates NY5 (5' half) and BRU (3' half).
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_04080}.
CC -!- SIMILARITY: Belongs to the HIV-1 VPR protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04080}.
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DR EMBL; K02013; AAB59749.1; -; Genomic_RNA.
DR BMRB; P05928; -.
DR SMR; P05928; -.
DR IntAct; P05928; 13.
DR iPTMnet; P05928; -.
DR Proteomes; UP000007692; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0043655; C:host extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0044423; C:virion component; IEA:UniProtKB-UniRule.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0019051; P:induction by virus of host apoptotic process; IEA:UniProtKB-UniRule.
DR GO; GO:0006811; P:ion transport; IEA:UniProtKB-UniRule.
DR GO; GO:0051260; P:protein homooligomerization; IEA:UniProtKB-UniRule.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-UniRule.
DR GO; GO:0039592; P:suppression by virus of G2/M transition of host mitotic cell cycle; IEA:UniProtKB-UniRule.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-UniRule.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0075732; P:viral penetration into host nucleus; IEA:UniProtKB-UniRule.
DR HAMAP; MF_04080; HIV_VPR; 1.
DR InterPro; IPR000012; RetroV_VpR/X.
DR Pfam; PF00522; VPR; 1.
DR PRINTS; PR00444; HIVVPRVPX.
PE 1: Evidence at protein level;
KW Activator; AIDS; Apoptosis; Cell cycle;
KW Host G2/M cell cycle arrest by virus; Host nucleus; Host-virus interaction;
KW Ion channel; Ion transport; Modulation of host cell cycle by virus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Transport; Viral penetration into host nucleus;
KW Virion; Virus entry into host cell.
FT CHAIN 1..96
FT /note="Protein Vpr"
FT /id="PRO_0000085439"
FT REGION 1..42
FT /note="Homooligomerization"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04080"
FT MOD_RES 79
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04080,
FT ECO:0000269|PubMed:10864665, ECO:0000269|PubMed:11860675"
FT MOD_RES 94
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04080,
FT ECO:0000269|PubMed:10864665"
FT MOD_RES 96
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04080,
FT ECO:0000269|PubMed:10864665"
FT VARIANT 15
FT /note="H -> Y (in strain: Clone pNL4-3)"
FT VARIANT 28
FT /note="N -> S (in strain: Clone pNL4-3)"
FT VARIANT 41
FT /note="G -> N (in strain: Clone pNL4-3)"
FT VARIANT 85
FT /note="Q -> R (in strain: Clone pNL4-3)"
FT MUTAGEN 17
FT /note="E->D: No effect."
FT /evidence="ECO:0000269|PubMed:10074177"
FT MUTAGEN 18
FT /note="W->R: Partial loss of cell killing."
FT /evidence="ECO:0000269|PubMed:10074177"
FT MUTAGEN 20..26
FT /note="LELLEEL->AEAAEEA: Partial loss of nuclear
FT localization."
FT /evidence="ECO:0000269|PubMed:9520381"
FT MUTAGEN 21
FT /note="E->Q: Partial loss of Na(+) permeability for ion
FT channel function."
FT /evidence="ECO:0000269|PubMed:10196319"
FT MUTAGEN 23
FT /note="L->F: 80% loss incorporation into virion. 10% loss
FT of LTR transactivation."
FT /evidence="ECO:0000269|PubMed:9837715"
FT MUTAGEN 24
FT /note="E->G: Partial loss of cell killing."
FT /evidence="ECO:0000269|PubMed:10074177,
FT ECO:0000269|PubMed:10196319"
FT MUTAGEN 24
FT /note="E->Q: Partial loss of Na(+) permeability for ion
FT channel function."
FT /evidence="ECO:0000269|PubMed:10074177,
FT ECO:0000269|PubMed:10196319"
FT MUTAGEN 25
FT /note="E->K: 75% loss incorporation into virion.
FT Perinuclear localization. Partial loss of cell killing. No
FT effect on human TFIIB binding."
FT /evidence="ECO:0000269|PubMed:10074177,
FT ECO:0000269|PubMed:10359081, ECO:0000269|PubMed:9837715"
FT MUTAGEN 30
FT /note="A->F: 80% loss incorporation into virion.
FT Perinuclear localization. 56% loss of LTR transactivation.
FT No effect on human TFIIB binding."
FT /evidence="ECO:0000269|PubMed:10359081,
FT ECO:0000269|PubMed:9520381, ECO:0000269|PubMed:9837715"
FT MUTAGEN 30
FT /note="A->L: Complete loss of G2/M cell cycle arrest."
FT /evidence="ECO:0000269|PubMed:10359081,
FT ECO:0000269|PubMed:9520381, ECO:0000269|PubMed:9837715"
FT MUTAGEN 32
FT /note="R->A: No effect on incorporation in virion."
FT /evidence="ECO:0000269|PubMed:8230445"
FT MUTAGEN 33
FT /note="H->R: Partial loss of nuclear localization, cell
FT killing and G2/M cell cycle arrest."
FT /evidence="ECO:0000269|PubMed:10074177"
FT MUTAGEN 34
FT /note="F->I: Partial loss of cell killing and nuclear
FT localization."
FT /evidence="ECO:0000269|PubMed:10074177"
FT MUTAGEN 54
FT /note="W->R: Partial loss of cell killing."
FT /evidence="ECO:0000269|PubMed:10074177"
FT MUTAGEN 57
FT /note="V->L: 25% loss incorporation into virion.
FT Perinuclear localization. No effect on human TFIIB
FT binding."
FT /evidence="ECO:0000269|PubMed:10359081,
FT ECO:0000269|PubMed:9837715"
FT MUTAGEN 58
FT /note="E->Q: No effect on ion channel activity."
FT /evidence="ECO:0000269|PubMed:10196319"
FT MUTAGEN 59
FT /note="A->P: Complete loss of G2/M cell cycle arrest."
FT /evidence="ECO:0000269|PubMed:9520381"
FT MUTAGEN 62
FT /note="R->A: No effect on incorporation in virion."
FT /evidence="ECO:0000269|PubMed:8230445,
FT ECO:0000269|PubMed:9837715"
FT MUTAGEN 62
FT /note="R->P: 30% loss incorporation into virion.
FT Perinuclear localization. 8% loss of LTR transactivation."
FT /evidence="ECO:0000269|PubMed:8230445,
FT ECO:0000269|PubMed:9837715"
FT MUTAGEN 63
FT /note="I->F: 10% loss incorporation into virion.
FT Perinuclear localization. 31% loss of LTR transactivation."
FT /evidence="ECO:0000269|PubMed:9837715"
FT MUTAGEN 63
FT /note="I->K: 35% loss incorporation into virion.
FT Perinuclear localization. 22% loss of LTR transactivation."
FT /evidence="ECO:0000269|PubMed:9837715"
FT MUTAGEN 67
FT /note="L->S: Partial loss of nuclear localization. Complete
FT loss of G2/M cell cycle arrest."
FT /evidence="ECO:0000269|PubMed:9520381"
FT MUTAGEN 68..70
FT /note="LFI->KFR: Complete loss of G2/M cell cycle arrest.
FT Perinuclear localization. 66% loss of LTR transactivation."
FT /evidence="ECO:0000269|PubMed:9837715"
FT MUTAGEN 71
FT /note="H->C: Complete loss of G2/M cell cycle arrest."
FT /evidence="ECO:0000269|PubMed:10074177,
FT ECO:0000269|PubMed:9520381"
FT MUTAGEN 71
FT /note="H->R: Partial loss of nuclear localization, cell
FT killing and G2/M cell cycle arrest."
FT /evidence="ECO:0000269|PubMed:10074177,
FT ECO:0000269|PubMed:9520381"
FT MUTAGEN 73
FT /note="R->A,S: Complete loss of LTR transactivation and of
FT G2/M cell cycle arrest. Transdominant mutation."
FT /evidence="ECO:0000269|PubMed:10775627"
FT MUTAGEN 75
FT /note="G->A: Complete loss of G2/M cell cycle arrest."
FT /evidence="ECO:0000269|PubMed:9520381"
FT MUTAGEN 76
FT /note="C->A: Complete loss of incorporation in virion."
FT /evidence="ECO:0000269|PubMed:8230445,
FT ECO:0000269|PubMed:9520381"
FT MUTAGEN 76
FT /note="C->S: Complete loss of G2/M cell cycle arrest."
FT /evidence="ECO:0000269|PubMed:8230445,
FT ECO:0000269|PubMed:9520381"
FT MUTAGEN 78
FT /note="H->R: Partial loss of G2/M cell cycle arrest."
FT /evidence="ECO:0000269|PubMed:10074177"
FT MUTAGEN 79
FT /note="S->A: Complete loss of cell cycle arrest."
FT /evidence="ECO:0000269|PubMed:10074177,
FT ECO:0000269|PubMed:10864665"
FT MUTAGEN 80..90
FT /note="RIGVTQQRRAR->NIGVTNQNNAN: Partial loss of nuclear
FT localization."
FT /evidence="ECO:0000269|PubMed:9514978"
FT MUTAGEN 80
FT /note="R->A: Complete loss of G2/M cell cycle arrest. 66%
FT loss of LTR transactivation. Complete loss of human TFIIB
FT binding."
FT /evidence="ECO:0000269|PubMed:10359081,
FT ECO:0000269|PubMed:9837715"
FT MUTAGEN 88
FT /note="R->K: Partial loss of G2/M cell cycle arrest."
FT /evidence="ECO:0000269|PubMed:10074177"
FT MUTAGEN 89
FT /note="A->T: No effect."
FT /evidence="ECO:0000269|PubMed:10074177"
FT MUTAGEN 90
FT /note="R->K: Partial loss of cell killing and G2/M cell
FT cycle arrest."
FT /evidence="ECO:0000269|PubMed:10074177"
FT MUTAGEN 94
FT /note="S->G: Partial loss of cell cycle arrest."
FT /evidence="ECO:0000269|PubMed:10864665"
FT MUTAGEN 95
FT /note="R->Q: No effect on ion channel activity."
FT /evidence="ECO:0000269|PubMed:10196319"
FT MUTAGEN 96
FT /note="S->P: No effect on cell cycle arrest."
FT /evidence="ECO:0000269|PubMed:10864665"
SQ SEQUENCE 96 AA; 11295 MW; 42892A4186E83D3E CRC64;
MEQAPEDQGP QREPHNEWTL ELLEELKNEA VRHFPRIWLH GLGQHIYETY GDTWAGVEAI
IRILQQLLFI HFRIGCRHSR IGVTQQRRAR NGASRS
