ID   REX_HTL1F               Reviewed;         189 AA.
AC   P0C207;
DT   14-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT   14-NOV-2006, sequence version 1.
DT   25-MAY-2022, entry version 43.
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 (isolate Zaire EL subtype B) (HTLV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Deltaretrovirus.
OX   NCBI_TaxID=39015;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2024459; DOI=10.1016/0042-6822(91)90654-t;
RA   Paine E., Garcia J., Philpott T.C., Shaw G., Ratner L.;
RT   "Limited sequence variation in human T-lymphotropic virus type 1 isolates
RT   from North American and African patients.";
RL   Virology 182:111-123(1991).
RN   [2]
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   [3]
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   [4]
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 (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Homomultimer. Multimeric assembly is essential for activity
CC       and involves XPO1. Binds to human XPO1 and KPNB1 (By similarity).
CC       Interacts (via N-terminal nuclear localization signal) with human NPM1.
CC       {ECO:0000250, ECO:0000269|PubMed:8314759}.
CC   -!- SUBCELLULAR LOCATION: [Isoform Rex]: Host nucleus, host nucleolus
CC       {ECO:0000250}. Host cytoplasm {ECO:0000250}. Note=The presence of both
CC       nuclear import and nuclear export signals leads to continuous shuttling
CC       between the nucleus and cytoplasm. {ECO:0000250}.
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=P0C207-1; Sequence=Displayed;
CC       Name=p21Rex; Synonyms=p21;
CC         IsoId=P0C207-2; Sequence=VSP_021541;
CC   -!- INDUCTION: Down-regulated by P30II.
CC   -!- DOMAIN: The RNA-binding motif binds to the RxRE, a complex secondary
CC       structure consisting of four stem loops and a long stretch of stem
CC       structure, present in incompletely spliced viral pre-mRNAs. This region
CC       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   -!- PTM: Phosphorylated. {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; M67514; -; NOT_ANNOTATED_CDS; Genomic_RNA.
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; RNA-binding; Transport.
FT   CHAIN           1..189
FT                   /note="Protein Rex"
FT                   /id="PRO_0000259784"
FT   REGION          1..28
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          56..70
FT                   /note="Homomultimerization"
FT                   /evidence="ECO:0000250"
FT   REGION          84..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                   /evidence="ECO:0000250"
FT   MOTIF           82..93
FT                   /note="Nuclear export signal"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        95..129
FT                   /note="Pro 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:0000250"
FT   MOD_RES         174
FT                   /note="Phosphothreonine; by host"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         177
FT                   /note="Phosphoserine; by host"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         1..78
FT                   /note="Missing (in isoform p21Rex)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_021541"
SQ   SEQUENCE   189 AA;  20503 MW;  99F8E55C3D99772C CRC64;
     MPKTRRRPRR SQRKRPPTPW PTSQGLDRVF FSDTQSTCLE TVYRATGAPS LGDYVRPVYI
     VTPYWPPVQS IRSPGTPSMD ALSAQLYSSL SLDSPPSPPR EPLRPSRSLP RRPPIQPPTF
     HPPSSRPCAN TPPSETDTWN PPLGSTSQPC LFQTPASGPK TCTPSGEAPL SACTSTSFPP
     PSPGPSCPT