ID   XPOT_HUMAN              Reviewed;         962 AA.
AC   O43592; A6NLH1; O43784; Q8WUG2; Q9BVS7;
DT   02-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2006, sequence version 2.
DT   27-MAR-2024, entry version 189.
DE   RecName: Full=Exportin-T;
DE   AltName: Full=Exportin(tRNA);
DE   AltName: Full=tRNA exportin;
GN   Name=XPOT;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 431-440 AND 739-752,
RP   FUNCTION IN TRNA EXPORT, IDENTIFICATION IN A COMPLEX WITH RAN AND TRNA,
RP   TRNA-BINDING, AND SUBCELLULAR LOCATION.
RC   TISSUE=Cervix carcinoma;
RX   PubMed=9660920; DOI=10.1016/s1097-2765(00)80036-2;
RA   Kutay U., Lipowsky G., Izaurralde E., Bischoff F.R., Schwarzmaier P.,
RA   Hartmann E., Goerlich D.;
RT   "Identification of a tRNA-specific nuclear export receptor.";
RL   Mol. Biol. Cell 1:359-369(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN TRNA EXPORT, IDENTIFICATION IN A
RP   COMPLEX WITH RAN AND TRNA, TRNA-BINDING, AND SUBCELLULAR LOCATION.
RC   TISSUE=Cervix carcinoma;
RX   PubMed=9512417; DOI=10.1016/s0960-9822(98)70130-7;
RA   Arts G.-J., Fornerod M., Mattaj I.W.;
RT   "Identification of a nuclear export receptor for tRNA.";
RL   Curr. Biol. 8:305-314(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16541075; DOI=10.1038/nature04569;
RA   Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA   Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA   Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA   Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA   Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA   Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA   Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA   Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA   Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA   Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA   Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA   Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA   Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA   Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA   Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA   Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA   Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA   David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA   D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA   Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA   Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA   Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA   LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA   Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA   Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA   Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA   Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA   Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA   Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA   Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA   Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA   Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA   Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA   Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA   Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA   Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA   Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA   Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA   Gibbs R.A.;
RT   "The finished DNA sequence of human chromosome 12.";
RL   Nature 440:346-351(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-526.
RC   TISSUE=Lymph, and Placenta;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   PROTEIN SEQUENCE OF 21-29; 54-65; 317-328; 360-369 AND 825-851, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=B-cell lymphoma;
RA   Bienvenut W.V.;
RL   Submitted (JUN-2005) to UniProtKB.
RN   [6]
RP   TRNA-BINDING.
RX   PubMed=9857198; DOI=10.1093/emboj/17.24.7430;
RA   Arts G.-J., Kuersten S., Romby P., Ehresmann B., Mattaj I.W.;
RT   "The role of exportin-t in selective nuclear export of mature tRNAs.";
RL   EMBO J. 17:7430-7441(1998).
RN   [7]
RP   FUNCTION IN TRNA EXPORT, MUTAGENESIS OF 405-ARG--LYS-409; 539-LYS--ARG-543;
RP   547-LEU--PHE-551; 548-PHE--VAL-552 AND 550-ARG--LYS-557, IDENTIFICATION IN
RP   COMPLEX WITH RAN AND TRNA, IDENTIFICATION IN COMPLEX WITH EXPORTINS,
RP   TRNA-BINDING, AND SUBCELLULAR LOCATION.
RX   PubMed=12138183; DOI=10.1128/mcb.22.16.5708-5720.2002;
RA   Kuersten S., Arts G.-J., Walther T.C., Englmeier L., Mattaj I.W.;
RT   "Steady-state nuclear localization of exportin-t involves RanGTP binding
RT   and two distinct nuclear pore complex interaction domains.";
RL   Mol. Cell. Biol. 22:5708-5720(2002).
RN   [8]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [9]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-634, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA   Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [11]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA   Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA   Giglione C.;
RT   "Comparative large-scale characterisation of plant vs. mammal proteins
RT   reveals similar and idiosyncratic N-alpha acetylation features.";
RL   Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN   [12]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC   -!- FUNCTION: Mediates the nuclear export of aminoacylated tRNAs. In the
CC       nucleus binds to tRNA and to the GTPase Ran in its active GTP-bound
CC       form. Docking of this trimeric complex to the nuclear pore complex
CC       (NPC) is mediated through binding to nucleoporins. Upon transit of a
CC       nuclear export complex into the cytoplasm, disassembling of the complex
CC       and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1,
CC       respectively) cause release of the tRNA from the export receptor. XPOT
CC       then return to the nuclear compartment and mediate another round of
CC       transport. The directionality of nuclear export is thought to be
CC       conferred by an asymmetric distribution of the GTP- and GDP-bound forms
CC       of Ran between the cytoplasm and nucleus. {ECO:0000269|PubMed:12138183,
CC       ECO:0000269|PubMed:9512417, ECO:0000269|PubMed:9660920}.
CC   -!- SUBUNIT: Found in a complex with XPOT, Ran and tRNA. Probably found in
CC       a complex with nucleoporins. Interacts with Ran and tRNA in a GTP-
CC       dependent manner. {ECO:0000269|PubMed:12138183,
CC       ECO:0000269|PubMed:9512417, ECO:0000269|PubMed:9660920}.
CC   -!- INTERACTION:
CC       O43592; O95678: KRT75; NbExp=3; IntAct=EBI-286683, EBI-2949715;
CC       O43592; P78424: POU6F2; NbExp=3; IntAct=EBI-286683, EBI-12029004;
CC       O43592; P62826: RAN; NbExp=3; IntAct=EBI-286683, EBI-286642;
CC       O43592; Q13595: TRA2A; NbExp=3; IntAct=EBI-286683, EBI-2685506;
CC   -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Nuclear, once bound to
CC       tRNA and Ran the complex translocates to the cytoplasm. Shuttles
CC       between the nucleus and the cytoplasm.
CC   -!- SIMILARITY: Belongs to the exportin family. {ECO:0000305}.
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DR   EMBL; AF039022; AAC39793.1; -; mRNA.
DR   EMBL; Y16414; CAA76202.1; -; mRNA.
DR   EMBL; AC135279; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC000950; AAH00950.1; -; mRNA.
DR   EMBL; BC020569; AAH20569.1; -; mRNA.
DR   CCDS; CCDS31852.1; -.
DR   RefSeq; NP_009166.2; NM_007235.4.
DR   RefSeq; XP_016874237.1; XM_017018748.1.
DR   AlphaFoldDB; O43592; -.
DR   SMR; O43592; -.
DR   BioGRID; 116420; 250.
DR   IntAct; O43592; 72.
DR   MINT; O43592; -.
DR   STRING; 9606.ENSP00000327821; -.
DR   ChEMBL; CHEMBL4105803; -.
DR   TCDB; 1.I.1.1.3; the nuclear pore complex (npc) family.
DR   GlyGen; O43592; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; O43592; -.
DR   MetOSite; O43592; -.
DR   PhosphoSitePlus; O43592; -.
DR   SwissPalm; O43592; -.
DR   BioMuta; XPOT; -.
DR   EPD; O43592; -.
DR   jPOST; O43592; -.
DR   MassIVE; O43592; -.
DR   MaxQB; O43592; -.
DR   PaxDb; 9606-ENSP00000327821; -.
DR   PeptideAtlas; O43592; -.
DR   ProteomicsDB; 49066; -.
DR   Pumba; O43592; -.
DR   Antibodypedia; 16571; 154 antibodies from 25 providers.
DR   DNASU; 11260; -.
DR   Ensembl; ENST00000332707.10; ENSP00000327821.5; ENSG00000184575.12.
DR   GeneID; 11260; -.
DR   KEGG; hsa:11260; -.
DR   MANE-Select; ENST00000332707.10; ENSP00000327821.5; NM_007235.6; NP_009166.2.
DR   UCSC; uc001ssb.4; human.
DR   AGR; HGNC:12826; -.
DR   CTD; 11260; -.
DR   DisGeNET; 11260; -.
DR   GeneCards; XPOT; -.
DR   HGNC; HGNC:12826; XPOT.
DR   HPA; ENSG00000184575; Low tissue specificity.
DR   MIM; 603180; gene.
DR   neXtProt; NX_O43592; -.
DR   OpenTargets; ENSG00000184575; -.
DR   PharmGKB; PA37419; -.
DR   VEuPathDB; HostDB:ENSG00000184575; -.
DR   eggNOG; KOG2021; Eukaryota.
DR   GeneTree; ENSGT00390000007890; -.
DR   HOGENOM; CLU_004414_1_0_1; -.
DR   InParanoid; O43592; -.
DR   OMA; HEMFLFG; -.
DR   OrthoDB; 2546268at2759; -.
DR   PhylomeDB; O43592; -.
DR   TreeFam; TF314001; -.
DR   PathwayCommons; O43592; -.
DR   Reactome; R-HSA-6784531; tRNA processing in the nucleus.
DR   SignaLink; O43592; -.
DR   SIGNOR; O43592; -.
DR   BioGRID-ORCS; 11260; 145 hits in 1167 CRISPR screens.
DR   ChiTaRS; XPOT; human.
DR   GeneWiki; XPOT; -.
DR   GenomeRNAi; 11260; -.
DR   Pharos; O43592; Tbio.
DR   PRO; PR:O43592; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; O43592; Protein.
DR   Bgee; ENSG00000184575; Expressed in stromal cell of endometrium and 179 other cell types or tissues.
DR   ExpressionAtlas; O43592; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0016363; C:nuclear matrix; IBA:GO_Central.
DR   GO; GO:0005643; C:nuclear pore; IBA:GO_Central.
DR   GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR   GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR   GO; GO:0000049; F:tRNA binding; IDA:UniProtKB.
DR   GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR   GO; GO:0006409; P:tRNA export from nucleus; IDA:UniProtKB.
DR   GO; GO:0071528; P:tRNA re-export from nucleus; IBA:GO_Central.
DR   Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 1.
DR   InterPro; IPR011989; ARM-like.
DR   InterPro; IPR016024; ARM-type_fold.
DR   InterPro; IPR013598; Exportin-1/Importin-b-like.
DR   InterPro; IPR045546; Exportin-T_C.
DR   InterPro; IPR001494; Importin-beta_N.
DR   InterPro; IPR040017; XPOT.
DR   PANTHER; PTHR15952:SF11; EXPORTIN-T; 1.
DR   PANTHER; PTHR15952; EXPORTIN-T/LOS1; 1.
DR   Pfam; PF19282; Exportin-T; 1.
DR   Pfam; PF03810; IBN_N; 1.
DR   Pfam; PF08389; Xpo1; 1.
DR   SMART; SM00913; IBN_N; 1.
DR   SUPFAM; SSF48371; ARM repeat; 1.
DR   Genevisible; O43592; HS.
PE   1: Evidence at protein level;
KW   Acetylation; Cytoplasm; Direct protein sequencing; Nucleus;
KW   Reference proteome; RNA-binding; Transport; tRNA-binding.
FT   CHAIN           1..962
FT                   /note="Exportin-T"
FT                   /id="PRO_0000204716"
FT   REGION          1..385
FT                   /note="Necessary for interaction with Ran, nuclear
FT                   localization and nuclear import"
FT   REGION          443..962
FT                   /note="Necessary for tRNA-binding, cytoplasmic localization
FT                   and nuclear export"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0007744|PubMed:19413330,
FT                   ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT   MOD_RES         634
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   VARIANT         526
FT                   /note="A -> V (in dbSNP:rs17851795)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_026528"
FT   VARIANT         716
FT                   /note="E -> D (in dbSNP:rs1051396)"
FT                   /id="VAR_048962"
FT   MUTAGEN         405..409
FT                   /note="RKQLK->AAQLA: Abolishes binding to tRNA. Does not
FT                   abolish shuttling behavior."
FT                   /evidence="ECO:0000269|PubMed:12138183"
FT   MUTAGEN         539..543
FT                   /note="KVRSR->AVRSA: Does not abolish binding to tRNA. Does
FT                   not abolish shuttling behavior."
FT                   /evidence="ECO:0000269|PubMed:12138183"
FT   MUTAGEN         547..551
FT                   /note="LFSRF->AFSRA: Does not abolish binding to tRNA. Does
FT                   not abolish shuttling behavior."
FT                   /evidence="ECO:0000269|PubMed:12138183"
FT   MUTAGEN         548..552
FT                   /note="FSRFV->ASRFA: Does not abolish binding to tRNA. Does
FT                   not abolish shuttling behavior."
FT                   /evidence="ECO:0000269|PubMed:12138183"
FT   MUTAGEN         550..557
FT                   /note="RFVKSLNK->AFVASLNA: Abolishes binding to tRNA. Does
FT                   not abolish shuttling behavior."
FT                   /evidence="ECO:0000269|PubMed:12138183"
FT   CONFLICT        360
FT                   /note="Q -> R (in Ref. 1; AAC39793)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   962 AA;  109964 MW;  2F407EEDEC7C2996 CRC64;
     MDEQALLGLN PNADSDFRQR ALAYFEQLKI SPDAWQVCAE ALAQRTYSDD HVKFFCFQVL
     EHQVKYKYSE LTTVQQQLIR ETLISWLQAQ MLNPQPEKTF IRNKAAQVFA LLFVTEYLTK
     WPKFFFDILS VVDLNPRGVD LYLRILMAID SELVDRDVVH TSEEARRNTL IKDTMREQCI
     PNLVESWYQI LQNYQFTNSE VTCQCLEVVG AYVSWIDLSL IANDRFINML LGHMSIEVLR
     EEACDCLFEV VNKGMDPVDK MKLVESLCQV LQSAGFFSID QEEDVDFLAR FSKLVNGMGQ
     SLIVSWSKLI KNGDIKNAQE ALQAIETKVA LMLQLLIHED DDISSNIIGF CYDYLHILKQ
     LTVLSDQQKA NVEAIMLAVM KKLTYDEEYN FENEGEDEAM FVEYRKQLKL LLDRLAQVSP
     ELLLASVRRV FSSTLQNWQT TRFMEVEVAI RLLYMLAEAL PVSHGAHFSG DVSKASALQD
     MMRTLVTSGV SSYQHTSVTL EFFETVVRYE KFFTVEPQHI PCVLMAFLDH RGLRHSSAKV
     RSRTAYLFSR FVKSLNKQMN PFIEDILNRI QDLLELSPPE NGHQSLLSSD DQLFIYETAG
     VLIVNSEYPA ERKQALMRNL LTPLMEKFKI LLEKLMLAQD EERQASLADC LNHAVGFASR
     TSKAFSNKQT VKQCGCSEVY LDCLQTFLPA LSCPLQKDIL RSGVRTFLHR MIICLEEEVL
     PFIPSASEHM LKDCEAKDLQ EFIPLINQIT AKFKIQVSPF LQQMFMPLLH AIFEVLLRPA
     EENDQSAALE KQMLRRSYFA FLQTVTGSGM SEVIANQGAE NVERVLVTVI QGAVEYPDPI
     AQKTCFIILS KLVELWGGKD GPVGFADFVY KHIVPACFLA PLKQTFDLAD AQTVLALSEC
     AVTLKTIHLK RGPECVQYLQ QEYLPSLQVA PEIIQEFCQA LQQPDAKVFK NYLKVFFQRA
     KP
//