VPR_HV1H2
ID VPR_HV1H2 Reviewed; 96 AA.
AC P69726; P05926; Q85577;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 04-FEB-2015, sequence version 2.
DT 03-AUG-2022, entry version 108.
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 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 FUNCTION.
RC STRAIN=isolate BRU/LAI;
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 [3]
RP SUBCELLULAR LOCATION.
RC STRAIN=isolate BRU/LAI;
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 [4]
RP SUBCELLULAR LOCATION.
RC STRAIN=isolate BRU/LAI;
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 [5]
RP HOMOOLIGOMERIZATION.
RX PubMed=7798208; DOI=10.1016/s0021-9258(18)31610-7;
RA Zhao L.J., Wang L., Mukherjee S., Narayan O.;
RT "Biochemical mechanism of HIV-1 Vpr function. Oligomerization mediated by
RT the N-terminal domain.";
RL J. Biol. Chem. 269:32131-32137(1994).
RN [6]
RP INTERACTION WITH P6-GAG.
RC STRAIN=isolate BRU/LAI;
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 [7]
RP FUNCTION.
RC STRAIN=isolate BRU/LAI;
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 [8]
RP FUNCTION.
RC STRAIN=isolate BRU/LAI;
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 [9]
RP INTERACTION WITH HUMAN UNG.
RC STRAIN=isolate BRU/LAI;
RX PubMed=9151883; DOI=10.1128/jvi.71.6.4842-4846.1997;
RA Selig L., Benichou S., Rogel M.E., Wu L.I., Vodicka M.A., Sire J.,
RA Benarous R., Emerman M.;
RT "Uracil DNA glycosylase specifically interacts with Vpr of both human
RT immunodeficiency virus type 1 and simian immunodeficiency virus of sooty
RT mangabeys, but binding does not correlate with cell cycle arrest.";
RL J. Virol. 71:4842-4846(1997).
RN [10]
RP INTERACTION WITH HUMAN RAD23A.
RC STRAIN=isolate BRU/LAI;
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 [11]
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 [12]
RP FUNCTION.
RX PubMed=11000244; DOI=10.1128/jvi.74.20.9717-9726.2000;
RA Patel C.A., Mukhtar M., Pomerantz R.J.;
RT "Human immunodeficiency virus type 1 Vpr induces apoptosis in human
RT neuronal cells.";
RL J. Virol. 74:9717-9726(2000).
RN [13]
RP PHOSPHORYLATION AT SER-79; 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 [14]
RP FUNCTION.
RC STRAIN=isolate BRU/LAI;
RX PubMed=12417576; DOI=10.1083/jcb.200203150;
RA McDonald D., Vodicka M.A., Lucero G., Svitkina T.M., Borisy G.G.,
RA Emerman M., Hope T.J.;
RT "Visualization of the intracellular behavior of HIV in living cells.";
RL J. Cell Biol. 159:441-452(2002).
RN [15]
RP PHOSPHORYLATION AT SER-79.
RC STRAIN=isolate BRU/LAI;
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 [16]
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 [17]
RP FUNCTION, AND SUBUNIT.
RC STRAIN=isolate BRU/LAI;
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 [18]
RP FUNCTION, AND SUBUNIT.
RC STRAIN=isolate BRU/LAI;
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 [19]
RP FUNCTION, AND INTERACTION WITH HOST DCAF1.
RC STRAIN=isolate BRU/LAI;
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 [20]
RP FUNCTION, AND INTERACTION WITH HOST DCAF1.
RC STRAIN=isolate BRU/LAI;
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).
RN [21]
RP REVIEW.
RX PubMed=24744753; DOI=10.3389/fmicb.2014.00127;
RA Guenzel C.A., Herate C., Benichou S.;
RT "HIV-1 Vpr-a still 'enigmatic multitasker'.";
RL Front. Microbiol. 5:1-13(2014).
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:12417576, ECO:0000269|PubMed:2136707}.
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 ECO:0000269|PubMed:11000244, ECO:0000269|PubMed:12417576,
CC ECO:0000269|PubMed:17314515, ECO:0000269|PubMed:17630831,
CC ECO:0000269|PubMed:23612978, ECO:0000269|PubMed:24116224,
CC ECO:0000269|PubMed:7474100, ECO:0000269|PubMed:7666531}.
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:17314515, ECO:0000269|PubMed:23612978,
CC ECO:0000269|PubMed:24116224, ECO:0000269|PubMed:7474102,
CC ECO:0000269|PubMed:7798208, ECO:0000269|PubMed:9151883,
CC ECO:0000269|PubMed:9371639}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000255|HAMAP-Rule:MF_04080,
CC ECO:0000269|PubMed:2139896, ECO:0000269|PubMed:8411357}. Host nucleus
CC {ECO:0000255|HAMAP-Rule:MF_04080, ECO:0000269|PubMed:8411357}. Host
CC extracellular space {ECO:0000255|HAMAP-Rule:MF_04080}.
CC Note=Incorporation into virion is dependent on p6 GAG sequences. Lacks
CC a canonical nuclear localization signal, thus import into nucleus may
CC function independently of the human importin pathway. Detected in high
CC quantity in the serum and cerebrospinal fluid of AIDS patient.
CC {ECO:0000255|HAMAP-Rule:MF_04080, ECO:0000269|PubMed:3040055}.
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: 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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB50261.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; K03455; AAB50261.1; ALT_FRAME; Genomic_RNA.
DR PDB; 4U1S; X-ray; 1.76 A; C=34-42.
DR PDBsum; 4U1S; -.
DR SMR; P69726; -.
DR IntAct; P69726; 4.
DR iPTMnet; P69726; -.
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-180689; APOBEC3G mediated resistance to HIV-1 infection.
DR Reactome; R-HSA-180897; Vpr-mediated induction of apoptosis by mitochondrial outer membrane permeabilization.
DR Reactome; R-HSA-180910; Vpr-mediated nuclear import of PICs.
DR Proteomes; UP000002241; Genome.
DR GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
DR GO; GO:0043655; C:host extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0044423; C:virion component; IEA:UniProtKB-UniRule.
DR GO; GO:0051701; P:biological process involved in interaction with host; IPI:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0019051; P:induction by virus of host apoptotic process; IDA:UniProtKB.
DR GO; GO:0006811; P:ion transport; IEA:UniProtKB-UniRule.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
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; IDA:UniProtKB.
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 3D-structure; 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_0000085451"
FT REGION 1..42
FT /note="Homooligomerization"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04080,
FT ECO:0000269|PubMed:7798208"
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"
SQ SEQUENCE 96 AA; 11323 MW; 42892A4249E83D3E CRC64;
MEQAPEDQGP QREPHNEWTL ELLEELKNEA VRHFPRIWLH GLGQHIYETY GDTWAGVEAI
IRILQQLLFI HFRIGCRHSR IGVTRQRRAR NGASRS
