REX_HTL1A
ID REX_HTL1A Reviewed; 189 AA.
AC P0C205;
DT 14-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2006, sequence version 1.
DT 25-MAY-2022, entry version 54.
DE RecName: Full=Protein Rex;
DE AltName: Full=Rev homolog;
DE AltName: Full=Rex-1;
DE AltName: Full=p27Rex;
OS Human T-cell leukemia virus 1 (strain Japan ATK-1 subtype A) (HTLV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Deltaretrovirus.
OX NCBI_TaxID=11926;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6304725; DOI=10.1073/pnas.80.12.3618;
RA Seiki M., Hattori S., Hirayama Y., Yoshida M.C.;
RT "Human adult T-cell leukemia virus: complete nucleotide sequence of the
RT provirus genome integrated in leukemia cell DNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:3618-3622(1983).
RN [2]
RP RNA-BINDING.
RX PubMed=1942257; DOI=10.1128/jvi.65.12.7051-7055.1991;
RA Boehnlein E., Berger J., Hauber J.;
RT "Functional mapping of the human immunodeficiency virus type 1 Rev RNA
RT binding domain: new insights into the domain structure of Rev and Rex.";
RL J. Virol. 65:7051-7055(1991).
RN [3]
RP PHOSPHORYLATION AT SER-70; SER-177 AND THR-174.
RX PubMed=1400509; DOI=10.1016/s0021-9258(19)36709-2;
RA Adachi Y., Copeland T.D., Takahashi C., Nosaka T., Ahmed A., Oroszlan S.,
RA Hatanaka M.;
RT "Phosphorylation of the Rex protein of human T-cell leukemia virus type
RT I.";
RL J. Biol. Chem. 267:21977-21981(1992).
RN [4]
RP SUBUNIT.
RX PubMed=1602559; DOI=10.1128/jvi.66.7.4540-4545.1992;
RA Weichselbraun I., Berger J., Dobrovnik M., Bogerd H., Grassmann R.,
RA Greene W.C., Hauber J., Boehnlein E.;
RT "Dominant-negative mutants are clustered in a domain of the human T-cell
RT leukemia virus type I Rex protein: implications for trans dominance.";
RL J. Virol. 66:4540-4545(1992).
RN [5]
RP ALTERNATIVE SPLICING (ISOFORMS REX AND P21REX).
RC STRAIN=Isolate LAF;
RX PubMed=1528897; DOI=10.1073/pnas.89.18.8813;
RA Koralnik I.J., Gessain A., Klotman M.E., Lo Monico A., Berneman Z.N.,
RA Franchini G.;
RT "Protein isoforms encoded by the pX region of human T-cell
RT leukemia/lymphotropic virus type I.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:8813-8817(1992).
RN [6]
RP INTERACTION WITH HUMAN NPM1.
RX PubMed=8314759; DOI=10.1016/s0021-9258(19)85191-8;
RA Adachi Y., Copeland T.D., Hatanaka M., Oroszlan S.;
RT "Nucleolar targeting signal of Rex protein of human T-cell leukemia virus
RT type I specifically binds to nucleolar shuttle protein B-23.";
RL J. Biol. Chem. 268:13930-13934(1993).
RN [7]
RP SUBUNIT.
RX PubMed=8474155; DOI=10.1128/jvi.67.5.2496-2502.1993;
RA Bogerd H., Greene W.C.;
RT "Dominant negative mutants of human T-cell leukemia virus type I Rex and
RT human immunodeficiency virus type 1 Rev fail to multimerize in vivo.";
RL J. Virol. 67:2496-2502(1993).
RN [8]
RP NUCLEAR EXPORT SIGNAL, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLN-85;
RP LEU-86; LEU-90 AND SER-91.
RX PubMed=8709278; DOI=10.1128/jvi.70.9.6442-6445.1996;
RA Palmeri D., Malim M.H.;
RT "The human T-cell leukemia virus type 1 posttranscriptional trans-activator
RT Rex contains a nuclear export signal.";
RL J. Virol. 70:6442-6445(1996).
RN [9]
RP NUCLEAR EXPORT SIGNAL.
RX PubMed=10339570; DOI=10.1073/pnas.96.11.6229;
RA Elfgang C., Rosorius O., Hofer L., Jaksche H., Hauber J., Bevec D.;
RT "Evidence for specific nucleocytoplasmic transport pathways used by
RT leucine-rich nuclear export signals.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:6229-6234(1999).
RN [10]
RP INTERACTION WITH HUMAN KPNB1.
RX PubMed=9891056; DOI=10.1128/mcb.19.2.1218;
RA Palmeri D., Malim M.H.;
RT "Importin beta can mediate the nuclear import of an arginine-rich nuclear
RT localization signal in the absence of importin alpha.";
RL Mol. Cell. Biol. 19:1218-1225(1999).
RN [11]
RP INTERACTION WITH HUMAN XPO1, IDENTIFICATION IN A COMPLEX WITH HUMAN XPO1;
RP RANBP3 AND RAN, AND SUBUNIT.
RX PubMed=14612415; DOI=10.1128/mcb.23.23.8751-8761.2003;
RA Hakata Y., Yamada M., Shida H.;
RT "A multifunctional domain in human CRM1 (exportin 1) mediates RanBP3
RT binding and multimerization of human T-cell leukemia virus type 1 Rex
RT protein.";
RL Mol. Cell. Biol. 23:8751-8761(2003).
RN [12]
RP DOWN-REGULATION BY P30II.
RX PubMed=14730358; DOI=10.1038/nm984;
RA Nicot C., Dundr M., Johnson J.M., Fullen J.R., Alonzo N., Fukumoto R.,
RA Princler G.L., Derse D., Misteli T., Franchini G.;
RT "HTLV-1-encoded p30II is a post-transcriptional negative regulator of viral
RT replication.";
RL Nat. Med. 10:197-201(2004).
RN [13]
RP REVIEW.
RX PubMed=15574380; DOI=10.2741/1539;
RA Younis I., Green P.L.;
RT "The human T-cell leukemia virus Rex protein.";
RL Front. Biosci. 10:431-445(2005).
RN [14]
RP REVIEW.
RX PubMed=16155601; DOI=10.1038/sj.onc.1208973;
RA Kashanchi F., Brady J.N.;
RT "Transcriptional and post-transcriptional gene regulation of HTLV-1.";
RL Oncogene 24:5938-5951(2005).
CC -!- FUNCTION: Rex escorts unspliced gag-pro-pol and singly spliced env
CC mRNAs out of the nucleus of infected cells. These mRNAs carry a
CC recognition sequence called Rex responsive element (RxRE or XRE)
CC located at the 3' region of the long terminal repeat (LTR). This
CC function is essential since most HTLV proteins are translated from
CC unspliced or partially spliced pre-mRNAs that cannot exit the nucleus
CC by the pathway used by fully processed cellular mRNAs. Rex itself is
CC translated from a fully spliced mRNA that probably readily exits the
CC nucleus. Rex's nuclear localization signal (NLS) binds directly to
CC KPNB1/importin beta-1 without previous binding to KPNA1/importin alpha-
CC 1. KPNB1 binds to the GDP bound form of RAN (Ran-GDP) and targets Rex
CC to the nucleus. In the nucleus, the conversion from Ran-GDP to Ran-GTP
CC dissociates Rex from KPNB1 and allows Rex's binding to the RRE in viral
CC pre-mRNAs. Rex multimerizes on the RRE via cooperative assembly. This
CC multimerization is critical for its full biological activity, since it
CC may shield the viral RNA from being spliced or down-regulated, and
CC probably exposes Rex's nuclear export signal (NES) to the surface. Rex
CC can then form a complex with XPO1/CRM1, RANBP3 and Ran-GTP, leading to
CC nuclear export of the complex. Conversion from Ran-GTP to Ran-GDP
CC mediates dissociation of the Rex/RRE/XPO1/RANBP3/RAN complex, so that
CC Rex can return to the nucleus for a subsequent round of export
CC (Probable). {ECO:0000305}.
CC -!- SUBUNIT: Homomultimer. Multimeric assembly is essential for activity
CC and involves XPO1. Binds to human XPO1 and KPNB1. Interacts (via N-
CC terminal nuclear localization signal) with human NPM1.
CC {ECO:0000269|PubMed:14612415, ECO:0000269|PubMed:1602559,
CC ECO:0000269|PubMed:8314759, ECO:0000269|PubMed:8474155,
CC ECO:0000269|PubMed:9891056}.
CC -!- INTERACTION:
CC P0C205; Q9UPY3: DICER1; Xeno; NbExp=7; IntAct=EBI-8332963, EBI-395506;
CC -!- SUBCELLULAR LOCATION: [Isoform Rex]: Host nucleus, host nucleolus. Host
CC cytoplasm. Note=The presence of both nuclear import and nuclear export
CC signals leads to continuous shuttling between the nucleus and
CC cytoplasm.
CC -!- SUBCELLULAR LOCATION: [Isoform p21Rex]: Host cytoplasm {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Rex; Synonyms=p27Rex;
CC IsoId=P0C205-1; Sequence=Displayed;
CC Name=p21Rex; Synonyms=p21;
CC IsoId=P0C205-2; Sequence=VSP_021539;
CC -!- INDUCTION: Down-regulated by P30II.
CC -!- DOMAIN: The RNA-binding motif of Rex binds to the RxRE, a complex
CC secondary structure consisting of four stem loops and a long stretch of
CC stem structure, present in incompletely spliced viral pre-mRNAs. This
CC region also contains the NLS which mediates nuclear localization. These
CC overlapping functions prevent Rex bound to RxRE from undesirable return
CC to the nucleus. When Rex binds the RxRE, the NLS becomes masked while
CC the NES remains accessible. The leucine-rich NES mediates binding to
CC human XPO1 (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: HTLV-1 lineages are divided in four clades, A
CC (Cosmopolitan), B (Central African group), C (Melanesian group) and D
CC (New Central African group).
CC -!- SIMILARITY: Belongs to the deltaretrovirus Rex protein family.
CC {ECO:0000305}.
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DR EMBL; J02029; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR ELM; P0C205; -.
DR IntAct; P0C205; 1.
DR MINT; P0C205; -.
DR iPTMnet; P0C205; -.
DR Proteomes; UP000007683; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0044196; C:host cell nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW Alternative splicing; Host cytoplasm; Host nucleus; Host-virus interaction;
KW mRNA transport; Phosphoprotein; Reference proteome; RNA-binding; Transport.
FT CHAIN 1..189
FT /note="Protein Rex"
FT /id="PRO_0000259782"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 56..70
FT /note="Homomultimerization"
FT /evidence="ECO:0000250"
FT REGION 73..189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 123..131
FT /note="Homomultimerization"
FT /evidence="ECO:0000250"
FT MOTIF 2..18
FT /note="Nuclear localization signal, and RNA-binding (RxRE)"
FT MOTIF 82..93
FT /note="Nuclear export signal"
FT COMPBIAS 73..94
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 130..161
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 70
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:1400509"
FT MOD_RES 174
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000269|PubMed:1400509"
FT MOD_RES 177
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000269|PubMed:1400509"
FT VAR_SEQ 1..78
FT /note="Missing (in isoform p21Rex)"
FT /evidence="ECO:0000305"
FT /id="VSP_021539"
FT MUTAGEN 85
FT /note="Q->A: No effect on mRNA export."
FT /evidence="ECO:0000269|PubMed:8709278"
FT MUTAGEN 85
FT /note="Q->P: Complete loss of mRNA export."
FT /evidence="ECO:0000269|PubMed:8709278"
FT MUTAGEN 86
FT /note="L->A: Complete loss of mRNA export; when associated
FT with A-90."
FT /evidence="ECO:0000269|PubMed:8709278"
FT MUTAGEN 90
FT /note="L->A: Complete loss of mRNA export; when associated
FT with A-86."
FT /evidence="ECO:0000269|PubMed:8709278"
FT MUTAGEN 91
FT /note="S->P: Complete loss of mRNA export."
FT /evidence="ECO:0000269|PubMed:8709278"
SQ SEQUENCE 189 AA; 20499 MW; 3DA522C115C6E233 CRC64;
MPKTRRRPRR SQRKRPPTPW PTSQGLDRVF FSDTQSTCLE TVYKATGAPS LGDYVRPAYI
VTPYWPPVQS IRSPGTPSMD ALSAQLYSSL SLDSPPSPPR EPLRPSRSLP RQSLIQPPTF
HPPSSRPCAN TPPSEMDTWN PPLGSTSQPC LFQTPDSGPK TCTPSGEAPL SACTSTSFPP
PSPGPSCPT
