REX_HTL1C
ID REX_HTL1C Reviewed; 189 AA.
AC P0C206; O56230;
DT 14-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2006, sequence version 1.
DT 03-AUG-2022, entry version 65.
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 Caribbea HS-35 subtype A) (HTLV-1).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Deltaretrovirus.
OX NCBI_TaxID=11927;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2899128; DOI=10.1099/0022-1317-69-7-1695;
RA Malik K.T.A., Even J., Karpas A.;
RT "Molecular cloning and complete nucleotide sequence of an adult T cell
RT leukaemia virus/human T cell leukaemia virus type I (ATLV/HTLV-I) isolate
RT of Caribbean origin: relationship to other members of the ATLV/HTLV-I
RT subgroup.";
RL J. Gen. Virol. 69:1695-1710(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Chappey C.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
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 [5]
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 -!- INTERACTION:
CC P0C206; O14503: BHLHE40; Xeno; NbExp=3; IntAct=EBI-9675596, EBI-711810;
CC P0C206; Q96FJ2: DYNLL2; Xeno; NbExp=4; IntAct=EBI-9675596, EBI-742371;
CC P0C206; Q8N448: LNX2; Xeno; NbExp=4; IntAct=EBI-9675596, EBI-2340947;
CC P0C206; Q9BRK4: LZTS2; Xeno; NbExp=4; IntAct=EBI-9675596, EBI-741037;
CC P0C206; Q6PF05: TTC23L; Xeno; NbExp=3; IntAct=EBI-9675596, EBI-8656864;
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=P0C206-1; Sequence=Displayed;
CC Name=p21Rex; Synonyms=p21;
CC IsoId=P0C206-2; Sequence=VSP_021540;
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC82584.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; D13784; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF033817; AAC82584.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; NP_057863.1; NC_001436.1.
DR PDB; 1EXY; NMR; -; B=1-16.
DR PDBsum; 1EXY; -.
DR SMR; P0C206; -.
DR IntAct; P0C206; 18.
DR MINT; P0C206; -.
DR iPTMnet; P0C206; -.
DR GeneID; 1491937; -.
DR KEGG; vg:1491937; -.
DR Proteomes; UP000001061; Genome.
DR Proteomes; UP000110593; 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 3D-structure; Alternative splicing; Host cytoplasm; Host nucleus;
KW Host-virus interaction; mRNA transport; Phosphoprotein; Reference proteome;
KW RNA-binding; Transport.
FT CHAIN 1..189
FT /note="Protein Rex"
FT /id="PRO_0000259783"
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 87..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 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_021540"
FT HELIX 10..12
FT /evidence="ECO:0007829|PDB:1EXY"
SQ SEQUENCE 189 AA; 20555 MW; D47A22D76F7A2449 CRC64;
MPKTRRRPRR SQRKRPPTPW PTSQGLDRVF FSDTQSTCLE TVYKATGAPS LGDYVRPAYI
VTPYWPPVQS IRSPGTPSMD ALSAQLYSSL SLDSPPSPPR EPLRPLRSLP RQSLIQPPTF
HPPSSRPCAN TPPSEMDTWN PPLGSTSQPC LFQTPDSGPK TCTPSGEAPL SACTSTSFPP
PSPGPSCPM
