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VPR_HV1MN
ID   VPR_HV1MN               Reviewed;          96 AA.
AC   P05950;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1988, sequence version 1.
DT   03-AUG-2022, entry version 126.
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 MN) (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX   NCBI_TaxID=11696;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=3369091; DOI=10.1016/0042-6822(88)90568-5;
RA   Gurgo C., Guo H.-G., Franchini G., Aldovini A., Collalti E., Farrell K.,
RA   Wong-Staal F., Gallo R.C., Reitz M.S. Jr.;
RT   "Envelope sequences of two new United States HIV-1 isolates.";
RL   Virology 164:531-536(1988).
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   -!- 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}.
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   -!- 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   -!- 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; M17449; AAA44855.1; -; Genomic_RNA.
DR   BMRB; P05950; -.
DR   SMR; P05950; -.
DR   Proteomes; UP000007697; 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   3: Inferred from homology;
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_0000085444"
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   MOD_RES         94
FT                   /note="Phosphoserine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04080"
FT   MOD_RES         96
FT                   /note="Phosphoserine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04080"
SQ   SEQUENCE   96 AA;  11344 MW;  2995312E2579935E CRC64;
     MEQAPEDQGP QREPYNQWAL ELLEELKNEA VRHFPRIWLH GLGQHIYETY GDTWAGVEAI
     IRILQQLLFI HFRIGCRHSR IGIIRQRRAR NGASRS
 
 
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