P0C205 (REX_HTL1A) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Protein Rex Alternative name(s): Rev homolog Rex-1 p27Rex
Organism	Human T-cell leukemia virus 1 (strain Japan ATK-1 subtype A) (HTLV-1) [Complete proteome]
Taxonomic identifier	11926 [NCBI]
Taxonomic lineage	Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Deltaretrovirus › Primate T-lymphotropic virus 1 › Human T-lymphotropic virus 1 › HTLV-1 subtype A
Virus host	Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	189 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Rex escorts unspliced gag-pro-pol and singly spliced env mRNAs out of the nucleus of infected cells. These mRNAs carry a recognition sequence called Rex responsive element (RxRE or XRE) located at the 3' region of the long terminal repeat (LTR). This function is essential since most HTLV proteins are translated from unspliced or partially spliced pre-mRNAs that cannot exit the nucleus by the pathway used by fully processed cellular mRNAs. Rex itself is translated from a fully spliced mRNA that probably readily exits the nucleus. Rex's nuclear localization signal (NLS) binds directly to KPNB1/importin beta-1 without previous binding to KPNA1/importin alpha-1. KPNB1 binds to the GDP bound form of RAN (Ran-GDP) and targets Rex to the nucleus. In the nucleus, the conversion from Ran-GDP to Ran-GTP dissociates Rex from KPNB1 and allows Rex's binding to the RRE in viral pre-mRNAs. Rex multimerizes on the RRE via cooperative assembly. This multimerization is critical for its full biological activity, since it may shield the viral RNA from being spliced or down-regulated, and probably exposes Rex's nuclear export signal (NES) to the surface. Rex can then form a complex with XPO1/CRM1, RANBP3 and Ran-GTP, leading to nuclear export of the complex. Conversion from Ran-GTP to Ran-GDP mediates dissociation of the Rex/RRE/XPO1/RANBP3/RAN complex, so that Rex can return to the nucleus for a subsequent round of export Probable.
Subunit structure	Homomultimer. Multimeric assembly is essential for activity and involves XPO1. Binds to human XPO1 and KPNB1. Interacts (via N-terminal nuclear localization signal) with human NPM1. Ref.4 Ref.6 Ref.7 Ref.10 Ref.11
Subcellular location	Isoform Rex: Host nucleus › host nucleolus. Host cytoplasm. Note: The presence of both nuclear import and nuclear export signals leads to continuous shuttling between the nucleus and cytoplasm. Ref.8 Isoform p21Rex: Host cytoplasm Potential Ref.8.
Induction	Down-regulated by P30II. Ref.12
Domain	The RNA-binding motif of Rex binds to the RxRE, a complex secondary structure consisting of four stem loops and a long stretch of stem structure, present in incompletely spliced viral pre-mRNAs. This region also contains the NLS which mediates nuclear localization. These overlapping functions prevent Rex bound to RxRE from undesirable return to the nucleus. When Rex binds the RxRE, the NLS becomes masked while the NES remains accessible. The leucine-rich NES mediates binding to human XPO1 By similarity.
Miscellaneous	HTLV-1 lineages are divided in four clades, A (Cosmopolitan), B (Central African group), C (Melanesian group) and D (New Central African group).
Sequence similarities	Belongs to the deltaretrovirus Rex protein family.

Ontologies

Keywords
Biological process	Host-virus interaction Transport mRNA transport
Cellular component	Host cytoplasm Host nucleus
Coding sequence diversity	Alternative splicing
Ligand	RNA-binding
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological_process	mRNA transport Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell host cell nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Rex (identifier: P0C205-1)

Also known as: p27Rex;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform p21Rex (identifier: P0C205-2)

Also known as: p21;

The sequence of this isoform differs from the canonical sequence as follows:
     1-78: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 189	189	Protein Rex		PRO_0000259782
Regions
	Region	56 – 70	15	Homomultimerization By similarity
	Region	123 – 131	9	Homomultimerization By similarity
	Motif	2 – 18	17	Nuclear localization signal, and RNA-binding (RxRE)
	Motif	82 – 93	12	Nuclear export signal
	Compositional bias	95 – 188	94	Pro-rich
Amino acid modifications
	Modified residue	70	1	Phosphoserine; by host Ref.3
	Modified residue	174	1	Phosphothreonine; by host Ref.3
	Modified residue	177	1	Phosphoserine; by host Ref.3
Natural variations
	Alternative sequence	1 – 78	78	Missing in isoform p21Rex.		VSP_021539
Experimental info
	Mutagenesis	85	1	Q → A: No effect on mRNA export. Ref.8
	Mutagenesis	85	1	Q → P: Complete loss of mRNA export. Ref.8
	Mutagenesis	86	1	L → A: Complete loss of mRNA export; when associated with A-90. Ref.8
	Mutagenesis	90	1	L → A: Complete loss of mRNA export; when associated with A-86. Ref.8
	Mutagenesis	91	1	S → P: Complete loss of mRNA export. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform Rex (p27Rex) [UniParc]. Last modified November 14, 2006. Version 1. Checksum: 3DA522C115C6E233	FASTA	189	20,499
	10 20 30 40 50 60 MPKTRRRPRR SQRKRPPTPW PTSQGLDRVF FSDTQSTCLE TVYKATGAPS LGDYVRPAYI 70 80 90 100 110 120 VTPYWPPVQS IRSPGTPSMD ALSAQLYSSL SLDSPPSPPR EPLRPSRSLP RQSLIQPPTF 130 140 150 160 170 180 HPPSSRPCAN TPPSEMDTWN PPLGSTSQPC LFQTPDSGPK TCTPSGEAPL SACTSTSFPP PSPGPSCPT
	Isoform p21Rex (p21) [UniParc]. Checksum: F57B724A8D618093	FASTA	111	11,640
	10 20 30 40 50 60 MDALSAQLYS SLSLDSPPSP PREPLRPSRS LPRQSLIQPP TFHPPSSRPC ANTPPSEMDT 70 80 90 100 110 WNPPLGSTSQ PCLFQTPDSG PKTCTPSGEA PLSACTSTSF PPPSPGPSCP T

References

[1]	"Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA." Seiki M., Hattori S., Hirayama Y., Yoshida M.C. Proc. Natl. Acad. Sci. U.S.A. 80:3618-3622(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Functional mapping of the human immunodeficiency virus type 1 Rev RNA binding domain: new insights into the domain structure of Rev and Rex." Boehnlein E., Berger J., Hauber J. J. Virol. 65:7051-7055(1991) [PubMed] [Europe PMC] [Abstract] Cited for: RNA-BINDING.
[3]	"Phosphorylation of the Rex protein of human T-cell leukemia virus type I." Adachi Y., Copeland T.D., Takahashi C., Nosaka T., Ahmed A., Oroszlan S., Hatanaka M. J. Biol. Chem. 267:21977-21981(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-70; SER-177 AND THR-174.
[4]	"Dominant-negative mutants are clustered in a domain of the human T-cell leukemia virus type I Rex protein: implications for trans dominance." Weichselbraun I., Berger J., Dobrovnik M., Bogerd H., Grassmann R., Greene W.C., Hauber J., Boehnlein E. J. Virol. 66:4540-4545(1992) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[5]	"Protein isoforms encoded by the pX region of human T-cell leukemia/lymphotropic virus type I." Koralnik I.J., Gessain A., Klotman M.E., Lo Monico A., Berneman Z.N., Franchini G. Proc. Natl. Acad. Sci. U.S.A. 89:8813-8817(1992) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORMS REX AND P21REX). Strain: Isolate LAF.
[6]	"Nucleolar targeting signal of Rex protein of human T-cell leukemia virus type I specifically binds to nucleolar shuttle protein B-23." Adachi Y., Copeland T.D., Hatanaka M., Oroszlan S. J. Biol. Chem. 268:13930-13934(1993) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUMAN NPM1.
[7]	"Dominant negative mutants of human T-cell leukemia virus type I Rex and human immunodeficiency virus type 1 Rev fail to multimerize in vivo." Bogerd H., Greene W.C. J. Virol. 67:2496-2502(1993) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[8]	"The human T-cell leukemia virus type 1 posttranscriptional trans-activator Rex contains a nuclear export signal." Palmeri D., Malim M.H. J. Virol. 70:6442-6445(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEAR EXPORT SIGNAL, SUBCELLULAR LOCATION, MUTAGENESIS OF GLN-85; LEU-86; LEU-90 AND SER-91.
[9]	"Evidence for specific nucleocytoplasmic transport pathways used by leucine-rich nuclear export signals." Elfgang C., Rosorius O., Hofer L., Jaksche H., Hauber J., Bevec D. Proc. Natl. Acad. Sci. U.S.A. 96:6229-6234(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEAR EXPORT SIGNAL.
[10]	"Importin beta can mediate the nuclear import of an arginine-rich nuclear localization signal in the absence of importin alpha." Palmeri D., Malim M.H. Mol. Cell. Biol. 19:1218-1225(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUMAN KPNB1.
[11]	"A multifunctional domain in human CRM1 (exportin 1) mediates RanBP3 binding and multimerization of human T-cell leukemia virus type 1 Rex protein." Hakata Y., Yamada M., Shida H. Mol. Cell. Biol. 23:8751-8761(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUMAN XPO1, IDENTIFICATION IN A COMPLEX WITH HUMAN XPO1; RANBP3 AND RAN, SUBUNIT.
[12]	"HTLV-1-encoded p30II is a post-transcriptional negative regulator of viral replication." Nicot C., Dundr M., Johnson J.M., Fullen J.R., Alonzo N., Fukumoto R., Princler G.L., Derse D., Misteli T., Franchini G. Nat. Med. 10:197-201(2004) [PubMed] [Europe PMC] [Abstract] Cited for: DOWN-REGULATION BY P30II.
[13]	"The human T-cell leukemia virus Rex protein." Younis I., Green P.L. Front. Biosci. 10:431-445(2005) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[14]	"Transcriptional and post-transcriptional gene regulation of HTLV-1." Kashanchi F., Brady J.N. Oncogene 24:5938-5951(2005) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J02029 Genomic DNA. No translation available.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-7996809.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR004120. Tax. [Graphical view]
Pfam	PF02959. Tax. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

REX_HTL1A

Accession

Primary (citable) accession number: P0C205

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 14, 2006
Last sequence update:	November 14, 2006
Last modified:	May 29, 2013
This is version 27 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program