VPR_HV1C4
ID VPR_HV1C4 Reviewed; 16 AA.
AC P05953;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 29-SEP-2021, entry version 87.
DE RecName: Full=Protein Vpr;
DE AltName: Full=R ORF protein;
DE AltName: Full=Viral protein R;
DE Flags: Fragment;
GN Name=vpr;
OS Human immunodeficiency virus type 1 group M subtype B (isolate CDC-451)
OS (HIV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11687;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=3490666; DOI=10.1073/pnas.83.21.8380;
RA Desai S.M., Kalyanaraman V.S., Casey J.M., Srinivasan A., Andersen P.R.,
RA Devare S.G.;
RT "Molecular cloning and primary nucleotide sequence analysis of a distinct
RT human immunodeficiency virus isolate reveal significant divergence in its
RT genomic sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:8380-8384(1986).
CC -!- FUNCTION: Involved in the transport of the viral pre-integration (PIC)
CC complex to the nucleus during the early stages of the infection. This
CC function is crucial for viral infection of non-dividing macrophages.
CC May interact with karyopherin alpha/KPNA1 and KPNA2 to increase their
CC affinity for proteins containing basic-type nuclear localization
CC signal, including the viral matrix protein MA, thus facilitating the
CC translocation of the viral genome into the nucleus. May also act
CC directly at the nuclear pore complex, by binding nucleoporins
CC phenylalanine-glycine (FG)-repeat regions. Has an anti-apoptotic
CC effect, whereas high level of expression induces apoptosis. Interacts
CC with mitochondrial permeability transition pore complex (PTPC),
CC presumably through the binding of ANT proteins. This induces a rapid
CC dissipation of the mitochondrial transmembrane potential, and
CC mitochondrial release of apoptogenic proteins such as cytochrome C or
CC apoptosis inducing factors. Prevents infected cells from undergoing
CC mitosis and proliferating, by inducing arrest or delay in the G2 phase
CC of the cell cycle. The arrest in G2 is characterized by low levels of
CC CCNB1-CDC2 complex and corresponding inhibitory phosphorylation of
CC CDC2. Cell cycle arrest creates a favorable environment for maximizing
CC viral expression and production. This may be mediated by interacting
CC with and inhibiting human CDC25C, which normally activates the CCNB1-
CC CDC2 complex, or by binding SF3B2/SAP145. This function is independent
CC of nuclear localization. Cell cycle arrest reportedly occurs within
CC hours of infection and is not blocked by antiviral agents, suggesting
CC that it is initiated by the Vpr carried into the virion. Stimulates
CC gene expression driven by the HIV-1 LTR by interacting with human SP1,
CC TFIIB and TFIID. Moreover, the G2/M cell cycle arrest creates a
CC cellular environment where the HIV-1 LTR is transcriptionally more
CC active. Essential for unintegrated viral DNA expression. Detected in
CC the serum and cerebrospinal fluid of AIDS patient, where it may induce
CC cell death to bystander cells. This necrotic or apoptotic effect might
CC function by entering target cell plasma membrane to form ion channel
CC (By similarity). {ECO:0000250}.
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 C
CC terminus of the P6gag protein. Interacts with host SLC25A4/ANT1,
CC SLC25A5/ANT2, SLC25A6/ANT3, SP1, CDC25C, RAD23A/HHR23A, COPS6/HVIP,
CC TFIIB, UNG, SF3B2/SAP145, KPNA1 and KPNA2. Interacts with host
CC VPRBP/DCAF1, leading to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex,
CC mediate ubiquitination of host proteins such as TERT and ZGPAT and
CC arrest the cell cycle in G2 phase. Interacts with ANKHD1 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Virion. Host nucleus. Host extracellular space.
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 (By
CC similarity). {ECO:0000250}.
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).
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DR EMBL; M13137; AAA44308.1; -; Genomic_RNA.
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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006811; P:ion transport; IEA:UniProtKB-KW.
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-KW.
PE 3: Inferred from homology;
KW Activator; AIDS; Apoptosis; Cell cycle; Host nucleus;
KW Host-virus interaction; Ion channel; Ion transport; Transcription;
KW Transcription regulation; Transport; Viral penetration into host nucleus;
KW Virion; Virus entry into host cell.
FT CHAIN <1..16
FT /note="Protein Vpr"
FT /id="PRO_0000085440"
FT NON_TER 1
SQ SEQUENCE 16 AA; 1747 MW; 105A7C963EE29A56 CRC64;
NSATTAVYSF QDWVSA
