Full text data of XPO1
XPO1
(CRM1)
[Confidence: low (only semi-automatic identification from reviews)]
Exportin-1; Exp1 (Chromosome region maintenance 1 protein homolog)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Exportin-1; Exp1 (Chromosome region maintenance 1 protein homolog)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O14980
ID XPO1_HUMAN Reviewed; 1071 AA.
AC O14980; A6NL14; A8K1K5; D6W5E2; Q63HP8; Q68CP3; Q99433;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1998, sequence version 1.
DT 22-JAN-2014, entry version 134.
DE RecName: Full=Exportin-1;
DE Short=Exp1;
DE AltName: Full=Chromosome region maintenance 1 protein homolog;
GN Name=XPO1; Synonyms=CRM1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 757-765, INTERACTION
RP WITH NUP88 AND NUP214, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=9049309; DOI=10.1093/emboj/16.4.807;
RA Fornerod M., van Deursen J.M., van Baal S., Reynolds A., Davis D.,
RA Murti K.G., Fransen J., Grosveld G.;
RT "The human homologue of yeast CRM1 is in a dynamic subcomplex with
RT CAN/Nup214 and the novel nuclear pore component Nup88.";
RL EMBO J. 16:807-816(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Chronic myeloid leukemia cell;
RX PubMed=9368044; DOI=10.1074/jbc.272.47.29742;
RA Kudo N., Kohchbin S., Nishi K., Kitano K., Yanagida M., Yoshida M.,
RA Horinouchi S.;
RT "Molecular cloning and cell cycle-dependent expression of mammalian
RT CRM1, a protein involved in nuclear export of proteins.";
RL J. Biol. Chem. 272:29742-29751(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 45-54; 63-88; 105-112; 130-139; 159-190; 246-253;
RP 296-305; 407-415; 424-442; 459-474; 480-492; 516-531; 538-553;
RP 675-686; 701-722; 797-810; 873-883; 996-1012 AND 1017-1038, AND MASS
RP SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [9]
RP FUNCTION IN PROTEIN NUCLEAR EXPORT, AND IDENTIFICATION IN A NUCLEAR
RP EXPORT COMPLEX WITH RAN.
RX PubMed=9323133; DOI=10.1016/S0092-8674(00)80371-2;
RA Fornerod M., Ohno M., Yoshida M., Mattaj I.W.;
RT "CRM1 is an export receptor for leucine-rich nuclear export signals.";
RL Cell 90:1051-1060(1997).
RN [10]
RP FUNCTION IN PROTEIN NUCLEAR EXPORT.
RX PubMed=9311922; DOI=10.1126/science.278.5335.141;
RA Ossareh-Nazari B., Bachelerie F., Dargemont C.;
RT "Evidence for a role of CRM1 in signal-mediated nuclear protein
RT export.";
RL Science 278:141-144(1997).
RN [11]
RP FUNCTION IN HIV-1 REV EXPORT, IDENTIFICATION IN A COMPLEX WITH HIV-1
RP REV; HIV-1 REV RESPONSE ELEMENT AND RAN, AND INTERACTION WITH HIV-1
RP REV.
RX PubMed=9837918; DOI=10.1074/jbc.273.50.33414;
RA Askjaer P., Jensen T.H., Nilsson J., Englmeier L., Kjems J.;
RT "The specificity of the CRM1-Rev nuclear export signal interaction is
RT mediated by RanGTP.";
RL J. Biol. Chem. 273:33414-33422(1998).
RN [12]
RP IDENTIFICATION IN A NUCLEAR EXPORT RECEPTOR COMPLEX, INTERACTION WITH
RP IPO7; KPNB1 AND SNUPN, AND IDENTIFICATION IN A TRIMERIC EXPORT COMPLEX
RP WITH RAN AND SNUPN.
RX PubMed=10209022; DOI=10.1083/jcb.145.2.255;
RA Paraskeva E., Izaurralde E., Bischoff F.R., Huber J., Kutay U.,
RA Hartmann E., Luehrmann R., Goerlich D.;
RT "CRM1-mediated recycling of snurportin 1 to the cytoplasm.";
RL J. Cell Biol. 145:255-264(1999).
RN [13]
RP INTERACTION WITH EBV BMLF1.
RX PubMed=10400785;
RA Boyle S.M., Ruvolo V., Gupta A.K., Swaminathan S.;
RT "Association with the cellular export receptor CRM 1 mediates function
RT and intracellular localization of Epstein-Barr virus SM protein, a
RT regulator of gene expression.";
RL J. Virol. 73:6872-6881(1999).
RN [14]
RP INACTIVATION BY LMB.
RX PubMed=10430904; DOI=10.1073/pnas.96.16.9112;
RA Kudo N., Matsumori N., Taoka H., Fujiwara D., Schreiner E.P.,
RA Wolff B., Yoshida M., Horinouchi S.;
RT "Leptomycin B inactivates CRM1/exportin 1 by covalent modification at
RT a cysteine residue in the central conserved region.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:9112-9117(1999).
RN [15]
RP INTERACTION WITH NUPL2.
RX PubMed=10358091; DOI=10.1074/jbc.274.24.17309;
RA Farjot G., Sergeant A., Mikaelian I.;
RT "A new nucleoporin-like protein interacts with both HIV-1 Rev nuclear
RT export signal and CRM-1.";
RL J. Biol. Chem. 274:17309-17317(1999).
RN [16]
RP IDENTIFICATION IN A NUCLEAR EXPORT COMPLEX WITH RANBP3 AND RAN, AND
RP INTERACTION WITH RANBP3.
RX PubMed=11571268; DOI=10.1093/embo-reports/kve200;
RA Englmeier L., Fornerod M., Bischoff F.R., Petosa C., Mattaj I.W.,
RA Kutay U.;
RT "RanBP3 influences interactions between CRM1 and its nuclear protein
RT export substrates.";
RL EMBO Rep. 2:926-932(2001).
RN [17]
RP INTERACTION WITH INFLUENZA A NUCLEOPROTEIN.
RX PubMed=11119609; DOI=10.1128/JVI.75.1.408-419.2001;
RA Elton D., Simpson-Holley M., Archer K., Medcalf L., Hallam R.,
RA McCauley J., Digard P.;
RT "Interaction of the influenza virus nucleoprotein with the cellular
RT CRM1-mediated nuclear export pathway.";
RL J. Virol. 75:408-419(2001).
RN [18]
RP IDENTIFICATION IN A NUCLEAR EXPORT COMPLEX WITH RANBP3 AND RAN, AND
RP INTERACTION WITH RANBP3.
RX PubMed=11425870; DOI=10.1083/jcb.153.7.1391;
RA Lindsay M.E., Holaska J.M., Welch K., Paschal B.M., Macara I.G.;
RT "Ran-binding protein 3 is a cofactor for Crm1-mediated nuclear protein
RT export.";
RL J. Cell Biol. 153:1391-1402(2001).
RN [19]
RP INTERACTION WITH RANBP3.
RX PubMed=11932251; DOI=10.1074/jbc.C100620200;
RA Nemergut M.E., Lindsay M.E., Brownawell A.M., Macara I.G.;
RT "Ran-binding protein 3 links Crm1 to the Ran guanine nucleotide
RT exchange factor.";
RL J. Biol. Chem. 277:17385-17388(2002).
RN [20]
RP INTERACTION WITH HIV-1 REV.
RX PubMed=12134013; DOI=10.1128/JVI.76.16.8079-8089.2002;
RA Hakata Y., Yamada M., Mabuchi N., Shida H.;
RT "The carboxy-terminal region of the human immunodeficiency virus type
RT 1 protein Rev has multiple roles in mediating CRM1-related Rev
RT functions.";
RL J. Virol. 76:8079-8089(2002).
RN [21]
RP IDENTIFICATION IN A 60S RIBOSOMAL SUBUNIT COMPLEX WITH RAN AND NMD3,
RP AND INTERACTION WITH NMD3.
RX PubMed=12724356; DOI=10.1242/jcs.00464;
RA Thomas F., Kutay U.;
RT "Biogenesis and nuclear export of ribosomal subunits in higher
RT eukaryotes depend on the CRM1 export pathway.";
RL J. Cell Sci. 116:2409-2419(2003).
RN [22]
RP INTERACTION WITH TERT.
RX PubMed=12808100; DOI=10.1128/MCB.23.13.4598-4610.2003;
RA Haendeler J., Hoffmann J., Brandes R.P., Zeiher A.M., Dimmeler S.;
RT "Hydrogen peroxide triggers nuclear export of telomerase reverse
RT transcriptase via Src kinase family-dependent phosphorylation of
RT tyrosine 707.";
RL Mol. Cell. Biol. 23:4598-4610(2003).
RN [23]
RP FUNCTION IN HTLV-1 REX EXPORT, IDENTIFICATION IN A COMPLEX WITH HTLV-1
RP REX; RANBP3 AND RAN, INTERACTION WITH HTLV-1 REX AND RANBP3, AND
RP MUTAGENESIS OF SER-191; VAL-284; ASP-334; ILE-337; THR-346; VAL-402;
RP PRO-411; MET-412; PHE-414; ARG-474 AND HIS-481.
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 [24]
RP INTERACTION WITH DDX3X.
RX PubMed=15507209; DOI=10.1016/j.cell.2004.09.029;
RA Yedavalli V.S., Neuveut C., Chi Y.-H., Kleiman L., Jeang K.-T.;
RT "Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export
RT function.";
RL Cell 119:381-392(2004).
RN [25]
RP FUNCTION IN U3 SNORNA TRANSPORT, SUBCELLULAR LOCATION, AND
RP RNA-BINDING.
RX PubMed=15574332; DOI=10.1016/j.molcel.2004.11.013;
RA Boulon S., Verheggen C., Jady B.E., Girard C., Pescia C., Paul C.,
RA Ospina J.K., Kiss T., Matera A.G., Bordonne R., Bertrand E.;
RT "PHAX and CRM1 are required sequentially to transport U3 snoRNA to
RT nucleoli.";
RL Mol. Cell 16:777-787(2004).
RN [26]
RP INTERACTION WITH HIV-1 REV, AND SUBCELLULAR LOCATION.
RX PubMed=15632073; DOI=10.1128/MCB.25.2.728-739.2005;
RA Daelemans D., Costes S.V., Lockett S., Pavlakis G.N.;
RT "Kinetic and molecular analysis of nuclear export factor CRM1
RT association with its cargo in vivo.";
RL Mol. Cell. Biol. 25:728-739(2005).
RN [27]
RP INTERACTION WITH NEMF.
RX PubMed=16103875; DOI=10.1038/sj.onc.1208962;
RA Bi X., Jones T., Abbasi F., Lee H., Stultz B., Hursh D.A.,
RA Mortin M.A.;
RT "Drosophila caliban, a nuclear export mediator, can function as a
RT tumor suppressor in human lung cancer cells.";
RL Oncogene 24:8229-8239(2005).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [29]
RP INTERACTION WITH SERTAD2.
RX PubMed=18316374; DOI=10.1074/jbc.M708365200;
RA Cheong J.K., Gunaratnam L., Hsu S.I.;
RT "CRM1-mediated nuclear export is required for 26 S proteasome-
RT dependent degradation of the TRIP-Br2 proto-oncoprotein.";
RL J. Biol. Chem. 283:11661-11676(2008).
RN [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [32]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-446 AND LYS-693, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [33]
RP INTERACTION WITH BIRC5/SURVIVIN.
RX PubMed=20826784; DOI=10.1074/jbc.M110.152777;
RA Wang H., Holloway M.P., Ma L., Cooper Z.A., Riolo M., Samkari A.,
RA Elenitoba-Johnson K.S., Chin Y.E., Altura R.A.;
RT "Acetylation directs survivin nuclear localization to repress STAT3
RT oncogenic activity.";
RL J. Biol. Chem. 285:36129-36137(2010).
RN [34]
RP INTERACTION WITH DTNBP1, AND FUNCTION.
RX PubMed=20921223; DOI=10.1074/jbc.M110.107912;
RA Fei E., Ma X., Zhu C., Xue T., Yan J., Xu Y., Zhou J., Wang G.;
RT "Nucleocytoplasmic shuttling of dysbindin-1, a schizophrenia-related
RT protein, regulates synapsin I expression.";
RL J. Biol. Chem. 285:38630-38640(2010).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-391, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [36]
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.,
RA Buerckstuemmer T., 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 [37]
RP INTERACTION WITH ATF2.
RX PubMed=22275354; DOI=10.1074/jbc.M111.294272;
RA Hsu C.C., Hu C.D.;
RT "Critical role of N-terminal end-localized nuclear export signal in
RT regulation of activating transcription factor 2 (ATF2) subcellular
RT localization and transcriptional activity.";
RL J. Biol. Chem. 287:8621-8632(2012).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 707-1027, ELECTRON MICROSCOPY
RP (22 ANGSTROMS), IDENTIFICATION IN A NUCLEAR EXPORT COMPLEX WITH RAN,
RP AND MUTAGENESIS OF 428-GLU--ASP-447; 430-VAL--LYS-446;
RP 430-VAL--VAL-433; TYR-454; GLU-513; LEU-525; GLN-550; ARG-553;
RP PHE-554; PHE-561; LYS-568; PHE-572; MET-583 AND LYS-590.
RX PubMed=15574331; DOI=10.1016/j.molcel.2004.11.018;
RA Petosa C., Schoehn G., Askjaer P., Bauer U., Moulin M., Steuerwald U.,
RA Soler-Lopez M., Baudin F., Mattaj I.W., Mueller C.W.;
RT "Architecture of CRM1/Exportin1 suggests how cooperativity is achieved
RT during formation of a nuclear export complex.";
RL Mol. Cell 16:761-775(2004).
CC -!- FUNCTION: Mediates the nuclear export of cellular proteins
CC (cargos) bearing a leucine-rich nuclear export signal (NES) and of
CC RNAs. In the nucleus, in association with RANBP3, binds
CC cooperatively to the NES on its target protein and to the GTPase
CC RAN in its active GTP-bound form (Ran-GTP). Docking of this
CC complex to the nuclear pore complex (NPC) is mediated through
CC binding to nucleoporins. Upon transit of a nuclear export complex
CC into the cytoplasm, disassembling of the complex and hydrolysis of
CC Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively)
CC cause release of the cargo from the export receptor. The
CC directionality of nuclear export is thought to be conferred by an
CC asymmetric distribution of the GTP- and GDP-bound forms of Ran
CC between the cytoplasm and nucleus. Involved in U3 snoRNA transport
CC from Cajal bodies to nucleoli. Binds to late precursor U3 snoRNA
CC bearing a TMG cap. Several viruses, among them HIV-1, HTLV-1 and
CC influenza A use it to export their unspliced or incompletely
CC spliced RNAs out of the nucleus. Interacts with, and mediates the
CC nuclear export of HIV-1 Rev and HTLV-1 Rex proteins. Involved in
CC HTLV-1 Rex multimerization.
CC -!- SUBUNIT: Found in a U snRNA export complex with RNUXA/PHAX, NCBP1,
CC NCBP2, RAN, XPO1 and m7G-capped RNA (By similarity). Component of
CC a nuclear export receptor complex composed of KPNB1, RAN, SNUPN
CC and XPO1. Found in a trimeric export complex with SNUPN, RAN and
CC XPO1. Found in a nuclear export complex with RANBP3 and RAN. Found
CC in a 60S ribosomal subunit export complex with NMD3, RAN, XPO1.
CC Interacts with DDX3X, NMD3, NUPL2, NUP88, NUP214, RANBP3 and TERT.
CC Also found in complex with several viral proteins involved in
CC RNAs' nuclear export like HIV-1 Rev and HTLV-1 Rex. Interacts
CC presumably with influenza A nucleoprotein. Interacts with Epstein-
CC Barr virus BMLF1. Interacts with NEMF (via its N-terminus).
CC Interacts with the monomeric form of BIRC5/survivin deacetylated
CC at 'Lys-129'. Interacts with DTNBP1 and SERTAD2; the interactions
CC translocate DTNBP1 and SERTAD2 out of the nucleus. Interacts with
CC ATF2.
CC -!- INTERACTION:
CC O15392:BIRC5; NbExp=2; IntAct=EBI-355867, EBI-518823;
CC P04626:ERBB2; NbExp=2; IntAct=EBI-355867, EBI-641062;
CC P35232:PHB; NbExp=2; IntAct=EBI-355867, EBI-354213;
CC P61925:PKIA; NbExp=2; IntAct=EBI-355867, EBI-2682139;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleoplasm. Nucleus,
CC Cajal body. Nucleus, nucleolus. Note=Located in the nucleoplasm,
CC Cajal bodies and nucleoli. Shuttles between the nucleus/nucleolus
CC and the cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, placenta, lung,
CC liver, skeletal muscle, pancreas, spleen, thymus, prostate,
CC testis, ovary, small intestine, colon and peripheral blood
CC leukocytes. Not expressed in the kidney.
CC -!- MISCELLANEOUS: Cellular target of leptomycin B (LMB), a XPO1/CRM1
CC nuclear export inhibitor.
CC -!- SIMILARITY: Belongs to the exportin family.
CC -!- SIMILARITY: Contains 10 HEAT repeats.
CC -!- SIMILARITY: Contains 1 importin N-terminal domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/XPO1ID44168ch2p15.html";
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DR EMBL; Y08614; CAA69905.2; -; mRNA.
DR EMBL; D89729; BAA23415.1; -; mRNA.
DR EMBL; AK289920; BAF82609.1; -; mRNA.
DR EMBL; BX647758; CAH56174.1; -; mRNA.
DR EMBL; CR749840; CAH18695.1; -; mRNA.
DR EMBL; AC016727; AAY14949.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99993.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99994.1; -; Genomic_DNA.
DR EMBL; BC032847; AAH32847.1; -; mRNA.
DR RefSeq; NP_003391.1; NM_003400.3.
DR UniGene; Hs.370770; -.
DR PDB; 1W9C; X-ray; 2.30 A; A/B=707-1027.
DR PDB; 2L1L; NMR; -; B=504-630.
DR PDB; 3GB8; X-ray; 2.90 A; A=1-1071.
DR PDB; 4BSM; X-ray; 4.50 A; A=1-1032.
DR PDB; 4BSN; X-ray; 4.10 A; A=1-1032.
DR PDBsum; 1W9C; -.
DR PDBsum; 2L1L; -.
DR PDBsum; 3GB8; -.
DR PDBsum; 4BSM; -.
DR PDBsum; 4BSN; -.
DR ProteinModelPortal; O14980; -.
DR SMR; O14980; 53-1061.
DR DIP; DIP-33678N; -.
DR IntAct; O14980; 34.
DR MINT; MINT-5002192; -.
DR STRING; 9606.ENSP00000195419; -.
DR BindingDB; O14980; -.
DR ChEMBL; CHEMBL5661; -.
DR PhosphoSite; O14980; -.
DR PaxDb; O14980; -.
DR PRIDE; O14980; -.
DR DNASU; 7514; -.
DR Ensembl; ENST00000401558; ENSP00000384863; ENSG00000082898.
DR Ensembl; ENST00000404992; ENSP00000385942; ENSG00000082898.
DR Ensembl; ENST00000406957; ENSP00000385559; ENSG00000082898.
DR GeneID; 7514; -.
DR KEGG; hsa:7514; -.
DR UCSC; uc002sbh.3; human.
DR CTD; 7514; -.
DR GeneCards; GC02M061704; -.
DR HGNC; HGNC:12825; XPO1.
DR HPA; CAB010184; -.
DR MIM; 602559; gene.
DR neXtProt; NX_O14980; -.
DR PharmGKB; PA37418; -.
DR eggNOG; COG5101; -.
DR HOVERGEN; HBG052817; -.
DR InParanoid; O14980; -.
DR KO; K14290; -.
DR OMA; PQIGRIY; -.
DR OrthoDB; EOG7CZK4S; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR Reactome; REACT_71; Gene Expression.
DR SignaLink; O14980; -.
DR ChiTaRS; XPO1; human.
DR EvolutionaryTrace; O14980; -.
DR GeneWiki; XPO1; -.
DR GenomeRNAi; 7514; -.
DR NextBio; 29403; -.
DR PRO; PR:O14980; -.
DR ArrayExpress; O14980; -.
DR Bgee; O14980; -.
DR CleanEx; HS_XPO1; -.
DR Genevestigator; O14980; -.
DR GO; GO:0005642; C:annulate lamellae; IDA:UniProtKB.
DR GO; GO:0015030; C:Cajal body; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; TAS:ProtInc.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0030529; C:ribonucleoprotein complex; IDA:MGI.
DR GO; GO:0008565; F:protein transporter activity; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0005215; F:transporter activity; TAS:Reactome.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0075733; P:intracellular transport of virus; TAS:Reactome.
DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0016071; P:mRNA metabolic process; TAS:Reactome.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:Reactome.
DR GO; GO:0006611; P:protein export from nucleus; IEA:Ensembl.
DR GO; GO:0034504; P:protein localization to nucleus; IEA:Ensembl.
DR GO; GO:0010824; P:regulation of centrosome duplication; IEA:Ensembl.
DR GO; GO:0042176; P:regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0046825; P:regulation of protein export from nucleus; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome.
DR Gene3D; 1.25.10.10; -; 3.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR014877; CRM1_C_dom.
DR InterPro; IPR013598; Exportin-1/Importin-b-like.
DR InterPro; IPR001494; Importin-beta_N.
DR Pfam; PF08767; CRM1_C; 1.
DR Pfam; PF03810; IBN_N; 1.
DR Pfam; PF08389; Xpo1; 1.
DR SMART; SM01102; CRM1_C; 1.
DR SMART; SM00913; IBN_N; 1.
DR SUPFAM; SSF48371; SSF48371; 4.
DR PROSITE; PS50077; HEAT_REPEAT; FALSE_NEG.
DR PROSITE; PS50166; IMPORTIN_B_NT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Host-virus interaction; mRNA transport;
KW Nucleus; Phosphoprotein; Protein transport; Reference proteome;
KW Repeat; RNA-binding; Transport.
FT CHAIN 1 1071 Exportin-1.
FT /FTId=PRO_0000204705.
FT DOMAIN 46 112 Importin N-terminal.
FT REPEAT 217 240 HEAT 1.
FT REPEAT 241 277 HEAT 2.
FT REPEAT 354 472 HEAT 3.
FT REPEAT 515 553 HEAT 4.
FT REPEAT 560 597 HEAT 5.
FT REPEAT 602 639 HEAT 6.
FT REPEAT 775 813 HEAT 7.
FT REPEAT 885 916 HEAT 8.
FT REPEAT 917 954 HEAT 9.
FT REPEAT 1002 1039 HEAT 10.
FT REGION 1 679 Necessary for HTLV-1 Rex-mediated mRNA
FT export.
FT REGION 327 450 Interaction with Ran and nuclear export
FT complex formation.
FT REGION 411 481 Interaction with RANBP3.
FT REGION 411 414 Necessary for HTLV-1 Rex multimerization.
FT REGION 800 820 Interaction with HIV-1 Rev.
FT MOD_RES 391 391 Phosphoserine.
FT MOD_RES 446 446 N6-acetyllysine.
FT MOD_RES 448 448 Phosphothreonine (By similarity).
FT MOD_RES 450 450 Phosphoserine (By similarity).
FT MOD_RES 454 454 Phosphotyrosine (By similarity).
FT MOD_RES 693 693 N6-acetyllysine.
FT MUTAGEN 191 191 S->A: Does not abolish Rex-mediated mRNA
FT export.
FT MUTAGEN 284 284 V->E: Does not abolish Rex-mediated mRNA
FT export.
FT MUTAGEN 334 334 D->G: Does not abolish Rex-mediated mRNA
FT export.
FT MUTAGEN 337 337 I->L: Does not abolish Rex-mediated mRNA
FT export.
FT MUTAGEN 346 346 T->A: Does not abolish Rex-mediated mRNA
FT export.
FT MUTAGEN 402 402 V->I: Does not abolish Rex-mediated mRNA
FT export.
FT MUTAGEN 411 411 P->T: Strongly abolishes interaction with
FT Rex and RANBP3, abolishes Rex-mediated
FT mRNA export. Does not abolish interaction
FT with RANBP3; when associated with S-414.
FT Abolishes Rex multimerization; when
FT associated with S-414.
FT MUTAGEN 412 412 M->V: Does not abolish interaction with
FT Rex and RANBP3, and Rex-mediated mRNA
FT export.
FT MUTAGEN 414 414 F->S: Strongly abolishes interaction with
FT Rex and RANBP3, abolishes Rex-mediated
FT mRNA export. Does not abolish interaction
FT with RANBP3; when associated with T-411.
FT Abolishes Rex multimerization; when
FT associated with T-411.
FT MUTAGEN 428 447 EEVLVVENDQGEVVREFMKD->QQVLVVQNNQGQVVRQFMK
FT N: Abolishes Ran binding activity in
FT absence of cargo and abolishes partially
FT Ran binding activity in presence of
FT cargo.
FT MUTAGEN 430 446 VLVVENDQGEVVREFMK->DEDEENDQGEDEEEDDD:
FT Partially restores Ran binding activity
FT in presence of cargo.
FT MUTAGEN 430 433 VLVV->DEDE: Abolishes Ran binding
FT activity both in absence or presence of
FT cargo.
FT MUTAGEN 454 454 Y->A: Does not abolish Ran binding
FT activity and nuclear export complex
FT formation.
FT MUTAGEN 474 474 R->I: Strongly abolishes interaction with
FT Rex and RANBP3, abolishes Rex-mediated
FT mRNA export.
FT MUTAGEN 481 481 H->Q: Strongly abolishes interaction with
FT Rex and RANBP3, abolishes Rex-mediated
FT mRNA export.
FT MUTAGEN 513 513 E->A: Abolishes Ran binding activity and
FT nuclear export complex formation.
FT Abolishes Ran binding activity and
FT nuclear export complex formation; when
FT associated with A-553 and A-554.
FT MUTAGEN 525 525 L->A: Enhances Ran binding activity and
FT does not abolish nuclear export complex
FT formation. Does not abolish Ran binding
FT activity and partially abolish nuclear
FT export complex formation; when associated
FT with A-561. Does not abolish Ran binding
FT activity and partially abolish nuclear
FT export complex formation; when associated
FT with A-568 and A-572.
FT MUTAGEN 550 550 Q->A: Enhances Ran binding activity and
FT does not abolish nuclear export complex
FT formation; when associated with A-553 and
FT A-590.
FT MUTAGEN 553 553 R->A: Enhances Ran binding activity and
FT does not abolish nuclear export complex
FT formation; when associated with A-550 and
FT A-590. Abolishes Ran binding activity and
FT nuclear export complex formation; when
FT associated with A-513 and A-554.
FT MUTAGEN 554 554 F->A: Partially abolishes Ran binding
FT activity and does not abolish nuclear
FT export complex formation. Abolishes Ran
FT binding activity and nuclear export
FT complex formation; when associated with
FT A-561. Abolishes Ran binding activity and
FT nuclear export complex formation; when
FT associated with A-553 and A-513.
FT MUTAGEN 561 561 F->A: Abolishes Ran binding activity and
FT nuclear export complex formation.
FT Abolishes Ran binding activity and
FT nuclear export complex formation; when
FT associated with A-554. Does not abolish
FT Ran binding activity and partially
FT abolish nuclear export complex formation;
FT when associated with A-525.
FT MUTAGEN 568 568 K->A: Does not abolish Ran binding
FT activity and partially abolish nuclear
FT export complex formation; when associated
FT with A-525 and A-572.
FT MUTAGEN 572 572 F->A: Does not abolish Ran binding
FT activity and partially abolish nuclear
FT export complex formation; when associated
FT with A-525 and A-568.
FT MUTAGEN 583 583 M->A: Enhances Ran binding activity; when
FT associated with A-590.
FT MUTAGEN 590 590 K->A: Enhances Ran binding activity and
FT does not abolish nuclear export complex
FT formation. Enhances Ran binding activity
FT and does not abolish nuclear export
FT complex formation; when associated with
FT A-583. Enhances Ran binding activity and
FT does not abolish nuclear export complex
FT formation; when associated with A-550 and
FT A-553.
FT CONFLICT 406 406 R -> G (in Ref. 4; CAH56174).
FT CONFLICT 953 953 V -> G (in Ref. 4; CAH18695).
FT CONFLICT 989 989 L -> I (in Ref. 4; CAH56174).
FT HELIX 63 68
FT HELIX 76 89
FT HELIX 97 113
FT HELIX 124 141
FT TURN 142 145
FT HELIX 149 157
FT HELIX 161 175
FT HELIX 188 197
FT HELIX 199 215
FT HELIX 219 232
FT TURN 233 235
FT HELIX 238 242
FT STRAND 243 245
FT HELIX 246 253
FT TURN 254 256
FT HELIX 258 260
FT HELIX 261 273
FT HELIX 280 297
FT HELIX 304 310
FT HELIX 313 339
FT HELIX 341 343
FT HELIX 344 358
FT HELIX 363 383
FT HELIX 404 423
FT HELIX 448 467
FT HELIX 469 484
FT STRAND 485 488
FT HELIX 491 503
FT TURN 504 506
FT HELIX 510 530
FT HELIX 534 550
FT HELIX 552 557
FT HELIX 559 572
FT HELIX 580 595
FT HELIX 596 598
FT STRAND 605 608
FT HELIX 610 615
FT HELIX 618 622
FT HELIX 627 642
FT HELIX 647 674
FT HELIX 676 680
FT HELIX 682 702
FT HELIX 704 706
FT HELIX 711 713
FT HELIX 714 735
FT HELIX 738 741
FT HELIX 743 764
FT HELIX 769 775
FT HELIX 777 789
FT HELIX 793 795
FT HELIX 799 811
FT HELIX 812 818
FT HELIX 819 834
FT TURN 837 839
FT HELIX 842 858
FT HELIX 862 865
FT HELIX 868 881
FT STRAND 884 886
FT HELIX 887 906
FT HELIX 908 931
FT STRAND 932 934
FT HELIX 939 954
FT STRAND 964 966
FT HELIX 970 985
FT HELIX 991 1003
FT TURN 1004 1006
FT HELIX 1008 1023
FT TURN 1024 1026
FT TURN 1028 1030
FT HELIX 1031 1052
FT HELIX 1053 1055
SQ SEQUENCE 1071 AA; 123386 MW; FDB00C065DA2FB1D CRC64;
MPAIMTMLAD HAARQLLDFS QKLDINLLDN VVNCLYHGEG AQQRMAQEVL THLKEHPDAW
TRVDTILEFS QNMNTKYYGL QILENVIKTR WKILPRNQCE GIKKYVVGLI IKTSSDPTCV
EKEKVYIGKL NMILVQILKQ EWPKHWPTFI SDIVGASRTS ESLCQNNMVI LKLLSEEVFD
FSSGQITQVK SKHLKDSMCN EFSQIFQLCQ FVMENSQNAP LVHATLETLL RFLNWIPLGY
IFETKLISTL IYKFLNVPMF RNVSLKCLTE IAGVSVSQYE EQFVTLFTLT MMQLKQMLPL
NTNIRLAYSN GKDDEQNFIQ NLSLFLCTFL KEHDQLIEKR LNLRETLMEA LHYMLLVSEV
EETEIFKICL EYWNHLAAEL YRESPFSTSA SPLLSGSQHF DVPPRRQLYL PMLFKVRLLM
VSRMAKPEEV LVVENDQGEV VREFMKDTDS INLYKNMRET LVYLTHLDYV DTERIMTEKL
HNQVNGTEWS WKNLNTLCWA IGSISGAMHE EDEKRFLVTV IKDLLGLCEQ KRGKDNKAII
ASNIMYIVGQ YPRFLRAHWK FLKTVVNKLF EFMHETHDGV QDMACDTFIK IAQKCRRHFV
QVQVGEVMPF IDEILNNINT IICDLQPQQV HTFYEAVGYM IGAQTDQTVQ EHLIEKYMLL
PNQVWDSIIQ QATKNVDILK DPETVKQLGS ILKTNVRACK AVGHPFVIQL GRIYLDMLNV
YKCLSENISA AIQANGEMVT KQPLIRSMRT VKRETLKLIS GWVSRSNDPQ MVAENFVPPL
LDAVLIDYQR NVPAAREPEV LSTMAIIVNK LGGHITAEIP QIFDAVFECT LNMINKDFEE
YPEHRTNFFL LLQAVNSHCF PAFLAIPPTQ FKLVLDSIIW AFKHTMRNVA DTGLQILFTL
LQNVAQEEAA AQSFYQTYFC DILQHIFSVV TDTSHTAGLT MHASILAYMF NLVEEGKIST
SLNPGNPVNN QIFLQEYVAN LLKSAFPHLQ DAQVKLFVTG LFSLNQDIPA FKEHLRDFLV
QIKEFAGEDT SDLFLEEREI ALRQADEEKH KRQMSVPGIF NPHEIPEEMC D
//
ID XPO1_HUMAN Reviewed; 1071 AA.
AC O14980; A6NL14; A8K1K5; D6W5E2; Q63HP8; Q68CP3; Q99433;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1998, sequence version 1.
DT 22-JAN-2014, entry version 134.
DE RecName: Full=Exportin-1;
DE Short=Exp1;
DE AltName: Full=Chromosome region maintenance 1 protein homolog;
GN Name=XPO1; Synonyms=CRM1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 757-765, INTERACTION
RP WITH NUP88 AND NUP214, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=9049309; DOI=10.1093/emboj/16.4.807;
RA Fornerod M., van Deursen J.M., van Baal S., Reynolds A., Davis D.,
RA Murti K.G., Fransen J., Grosveld G.;
RT "The human homologue of yeast CRM1 is in a dynamic subcomplex with
RT CAN/Nup214 and the novel nuclear pore component Nup88.";
RL EMBO J. 16:807-816(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Chronic myeloid leukemia cell;
RX PubMed=9368044; DOI=10.1074/jbc.272.47.29742;
RA Kudo N., Kohchbin S., Nishi K., Kitano K., Yanagida M., Yoshida M.,
RA Horinouchi S.;
RT "Molecular cloning and cell cycle-dependent expression of mammalian
RT CRM1, a protein involved in nuclear export of proteins.";
RL J. Biol. Chem. 272:29742-29751(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 45-54; 63-88; 105-112; 130-139; 159-190; 246-253;
RP 296-305; 407-415; 424-442; 459-474; 480-492; 516-531; 538-553;
RP 675-686; 701-722; 797-810; 873-883; 996-1012 AND 1017-1038, AND MASS
RP SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [9]
RP FUNCTION IN PROTEIN NUCLEAR EXPORT, AND IDENTIFICATION IN A NUCLEAR
RP EXPORT COMPLEX WITH RAN.
RX PubMed=9323133; DOI=10.1016/S0092-8674(00)80371-2;
RA Fornerod M., Ohno M., Yoshida M., Mattaj I.W.;
RT "CRM1 is an export receptor for leucine-rich nuclear export signals.";
RL Cell 90:1051-1060(1997).
RN [10]
RP FUNCTION IN PROTEIN NUCLEAR EXPORT.
RX PubMed=9311922; DOI=10.1126/science.278.5335.141;
RA Ossareh-Nazari B., Bachelerie F., Dargemont C.;
RT "Evidence for a role of CRM1 in signal-mediated nuclear protein
RT export.";
RL Science 278:141-144(1997).
RN [11]
RP FUNCTION IN HIV-1 REV EXPORT, IDENTIFICATION IN A COMPLEX WITH HIV-1
RP REV; HIV-1 REV RESPONSE ELEMENT AND RAN, AND INTERACTION WITH HIV-1
RP REV.
RX PubMed=9837918; DOI=10.1074/jbc.273.50.33414;
RA Askjaer P., Jensen T.H., Nilsson J., Englmeier L., Kjems J.;
RT "The specificity of the CRM1-Rev nuclear export signal interaction is
RT mediated by RanGTP.";
RL J. Biol. Chem. 273:33414-33422(1998).
RN [12]
RP IDENTIFICATION IN A NUCLEAR EXPORT RECEPTOR COMPLEX, INTERACTION WITH
RP IPO7; KPNB1 AND SNUPN, AND IDENTIFICATION IN A TRIMERIC EXPORT COMPLEX
RP WITH RAN AND SNUPN.
RX PubMed=10209022; DOI=10.1083/jcb.145.2.255;
RA Paraskeva E., Izaurralde E., Bischoff F.R., Huber J., Kutay U.,
RA Hartmann E., Luehrmann R., Goerlich D.;
RT "CRM1-mediated recycling of snurportin 1 to the cytoplasm.";
RL J. Cell Biol. 145:255-264(1999).
RN [13]
RP INTERACTION WITH EBV BMLF1.
RX PubMed=10400785;
RA Boyle S.M., Ruvolo V., Gupta A.K., Swaminathan S.;
RT "Association with the cellular export receptor CRM 1 mediates function
RT and intracellular localization of Epstein-Barr virus SM protein, a
RT regulator of gene expression.";
RL J. Virol. 73:6872-6881(1999).
RN [14]
RP INACTIVATION BY LMB.
RX PubMed=10430904; DOI=10.1073/pnas.96.16.9112;
RA Kudo N., Matsumori N., Taoka H., Fujiwara D., Schreiner E.P.,
RA Wolff B., Yoshida M., Horinouchi S.;
RT "Leptomycin B inactivates CRM1/exportin 1 by covalent modification at
RT a cysteine residue in the central conserved region.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:9112-9117(1999).
RN [15]
RP INTERACTION WITH NUPL2.
RX PubMed=10358091; DOI=10.1074/jbc.274.24.17309;
RA Farjot G., Sergeant A., Mikaelian I.;
RT "A new nucleoporin-like protein interacts with both HIV-1 Rev nuclear
RT export signal and CRM-1.";
RL J. Biol. Chem. 274:17309-17317(1999).
RN [16]
RP IDENTIFICATION IN A NUCLEAR EXPORT COMPLEX WITH RANBP3 AND RAN, AND
RP INTERACTION WITH RANBP3.
RX PubMed=11571268; DOI=10.1093/embo-reports/kve200;
RA Englmeier L., Fornerod M., Bischoff F.R., Petosa C., Mattaj I.W.,
RA Kutay U.;
RT "RanBP3 influences interactions between CRM1 and its nuclear protein
RT export substrates.";
RL EMBO Rep. 2:926-932(2001).
RN [17]
RP INTERACTION WITH INFLUENZA A NUCLEOPROTEIN.
RX PubMed=11119609; DOI=10.1128/JVI.75.1.408-419.2001;
RA Elton D., Simpson-Holley M., Archer K., Medcalf L., Hallam R.,
RA McCauley J., Digard P.;
RT "Interaction of the influenza virus nucleoprotein with the cellular
RT CRM1-mediated nuclear export pathway.";
RL J. Virol. 75:408-419(2001).
RN [18]
RP IDENTIFICATION IN A NUCLEAR EXPORT COMPLEX WITH RANBP3 AND RAN, AND
RP INTERACTION WITH RANBP3.
RX PubMed=11425870; DOI=10.1083/jcb.153.7.1391;
RA Lindsay M.E., Holaska J.M., Welch K., Paschal B.M., Macara I.G.;
RT "Ran-binding protein 3 is a cofactor for Crm1-mediated nuclear protein
RT export.";
RL J. Cell Biol. 153:1391-1402(2001).
RN [19]
RP INTERACTION WITH RANBP3.
RX PubMed=11932251; DOI=10.1074/jbc.C100620200;
RA Nemergut M.E., Lindsay M.E., Brownawell A.M., Macara I.G.;
RT "Ran-binding protein 3 links Crm1 to the Ran guanine nucleotide
RT exchange factor.";
RL J. Biol. Chem. 277:17385-17388(2002).
RN [20]
RP INTERACTION WITH HIV-1 REV.
RX PubMed=12134013; DOI=10.1128/JVI.76.16.8079-8089.2002;
RA Hakata Y., Yamada M., Mabuchi N., Shida H.;
RT "The carboxy-terminal region of the human immunodeficiency virus type
RT 1 protein Rev has multiple roles in mediating CRM1-related Rev
RT functions.";
RL J. Virol. 76:8079-8089(2002).
RN [21]
RP IDENTIFICATION IN A 60S RIBOSOMAL SUBUNIT COMPLEX WITH RAN AND NMD3,
RP AND INTERACTION WITH NMD3.
RX PubMed=12724356; DOI=10.1242/jcs.00464;
RA Thomas F., Kutay U.;
RT "Biogenesis and nuclear export of ribosomal subunits in higher
RT eukaryotes depend on the CRM1 export pathway.";
RL J. Cell Sci. 116:2409-2419(2003).
RN [22]
RP INTERACTION WITH TERT.
RX PubMed=12808100; DOI=10.1128/MCB.23.13.4598-4610.2003;
RA Haendeler J., Hoffmann J., Brandes R.P., Zeiher A.M., Dimmeler S.;
RT "Hydrogen peroxide triggers nuclear export of telomerase reverse
RT transcriptase via Src kinase family-dependent phosphorylation of
RT tyrosine 707.";
RL Mol. Cell. Biol. 23:4598-4610(2003).
RN [23]
RP FUNCTION IN HTLV-1 REX EXPORT, IDENTIFICATION IN A COMPLEX WITH HTLV-1
RP REX; RANBP3 AND RAN, INTERACTION WITH HTLV-1 REX AND RANBP3, AND
RP MUTAGENESIS OF SER-191; VAL-284; ASP-334; ILE-337; THR-346; VAL-402;
RP PRO-411; MET-412; PHE-414; ARG-474 AND HIS-481.
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 [24]
RP INTERACTION WITH DDX3X.
RX PubMed=15507209; DOI=10.1016/j.cell.2004.09.029;
RA Yedavalli V.S., Neuveut C., Chi Y.-H., Kleiman L., Jeang K.-T.;
RT "Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export
RT function.";
RL Cell 119:381-392(2004).
RN [25]
RP FUNCTION IN U3 SNORNA TRANSPORT, SUBCELLULAR LOCATION, AND
RP RNA-BINDING.
RX PubMed=15574332; DOI=10.1016/j.molcel.2004.11.013;
RA Boulon S., Verheggen C., Jady B.E., Girard C., Pescia C., Paul C.,
RA Ospina J.K., Kiss T., Matera A.G., Bordonne R., Bertrand E.;
RT "PHAX and CRM1 are required sequentially to transport U3 snoRNA to
RT nucleoli.";
RL Mol. Cell 16:777-787(2004).
RN [26]
RP INTERACTION WITH HIV-1 REV, AND SUBCELLULAR LOCATION.
RX PubMed=15632073; DOI=10.1128/MCB.25.2.728-739.2005;
RA Daelemans D., Costes S.V., Lockett S., Pavlakis G.N.;
RT "Kinetic and molecular analysis of nuclear export factor CRM1
RT association with its cargo in vivo.";
RL Mol. Cell. Biol. 25:728-739(2005).
RN [27]
RP INTERACTION WITH NEMF.
RX PubMed=16103875; DOI=10.1038/sj.onc.1208962;
RA Bi X., Jones T., Abbasi F., Lee H., Stultz B., Hursh D.A.,
RA Mortin M.A.;
RT "Drosophila caliban, a nuclear export mediator, can function as a
RT tumor suppressor in human lung cancer cells.";
RL Oncogene 24:8229-8239(2005).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [29]
RP INTERACTION WITH SERTAD2.
RX PubMed=18316374; DOI=10.1074/jbc.M708365200;
RA Cheong J.K., Gunaratnam L., Hsu S.I.;
RT "CRM1-mediated nuclear export is required for 26 S proteasome-
RT dependent degradation of the TRIP-Br2 proto-oncoprotein.";
RL J. Biol. Chem. 283:11661-11676(2008).
RN [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [32]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-446 AND LYS-693, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [33]
RP INTERACTION WITH BIRC5/SURVIVIN.
RX PubMed=20826784; DOI=10.1074/jbc.M110.152777;
RA Wang H., Holloway M.P., Ma L., Cooper Z.A., Riolo M., Samkari A.,
RA Elenitoba-Johnson K.S., Chin Y.E., Altura R.A.;
RT "Acetylation directs survivin nuclear localization to repress STAT3
RT oncogenic activity.";
RL J. Biol. Chem. 285:36129-36137(2010).
RN [34]
RP INTERACTION WITH DTNBP1, AND FUNCTION.
RX PubMed=20921223; DOI=10.1074/jbc.M110.107912;
RA Fei E., Ma X., Zhu C., Xue T., Yan J., Xu Y., Zhou J., Wang G.;
RT "Nucleocytoplasmic shuttling of dysbindin-1, a schizophrenia-related
RT protein, regulates synapsin I expression.";
RL J. Biol. Chem. 285:38630-38640(2010).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-391, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [36]
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.,
RA Buerckstuemmer T., 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 [37]
RP INTERACTION WITH ATF2.
RX PubMed=22275354; DOI=10.1074/jbc.M111.294272;
RA Hsu C.C., Hu C.D.;
RT "Critical role of N-terminal end-localized nuclear export signal in
RT regulation of activating transcription factor 2 (ATF2) subcellular
RT localization and transcriptional activity.";
RL J. Biol. Chem. 287:8621-8632(2012).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 707-1027, ELECTRON MICROSCOPY
RP (22 ANGSTROMS), IDENTIFICATION IN A NUCLEAR EXPORT COMPLEX WITH RAN,
RP AND MUTAGENESIS OF 428-GLU--ASP-447; 430-VAL--LYS-446;
RP 430-VAL--VAL-433; TYR-454; GLU-513; LEU-525; GLN-550; ARG-553;
RP PHE-554; PHE-561; LYS-568; PHE-572; MET-583 AND LYS-590.
RX PubMed=15574331; DOI=10.1016/j.molcel.2004.11.018;
RA Petosa C., Schoehn G., Askjaer P., Bauer U., Moulin M., Steuerwald U.,
RA Soler-Lopez M., Baudin F., Mattaj I.W., Mueller C.W.;
RT "Architecture of CRM1/Exportin1 suggests how cooperativity is achieved
RT during formation of a nuclear export complex.";
RL Mol. Cell 16:761-775(2004).
CC -!- FUNCTION: Mediates the nuclear export of cellular proteins
CC (cargos) bearing a leucine-rich nuclear export signal (NES) and of
CC RNAs. In the nucleus, in association with RANBP3, binds
CC cooperatively to the NES on its target protein and to the GTPase
CC RAN in its active GTP-bound form (Ran-GTP). Docking of this
CC complex to the nuclear pore complex (NPC) is mediated through
CC binding to nucleoporins. Upon transit of a nuclear export complex
CC into the cytoplasm, disassembling of the complex and hydrolysis of
CC Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively)
CC cause release of the cargo from the export receptor. The
CC directionality of nuclear export is thought to be conferred by an
CC asymmetric distribution of the GTP- and GDP-bound forms of Ran
CC between the cytoplasm and nucleus. Involved in U3 snoRNA transport
CC from Cajal bodies to nucleoli. Binds to late precursor U3 snoRNA
CC bearing a TMG cap. Several viruses, among them HIV-1, HTLV-1 and
CC influenza A use it to export their unspliced or incompletely
CC spliced RNAs out of the nucleus. Interacts with, and mediates the
CC nuclear export of HIV-1 Rev and HTLV-1 Rex proteins. Involved in
CC HTLV-1 Rex multimerization.
CC -!- SUBUNIT: Found in a U snRNA export complex with RNUXA/PHAX, NCBP1,
CC NCBP2, RAN, XPO1 and m7G-capped RNA (By similarity). Component of
CC a nuclear export receptor complex composed of KPNB1, RAN, SNUPN
CC and XPO1. Found in a trimeric export complex with SNUPN, RAN and
CC XPO1. Found in a nuclear export complex with RANBP3 and RAN. Found
CC in a 60S ribosomal subunit export complex with NMD3, RAN, XPO1.
CC Interacts with DDX3X, NMD3, NUPL2, NUP88, NUP214, RANBP3 and TERT.
CC Also found in complex with several viral proteins involved in
CC RNAs' nuclear export like HIV-1 Rev and HTLV-1 Rex. Interacts
CC presumably with influenza A nucleoprotein. Interacts with Epstein-
CC Barr virus BMLF1. Interacts with NEMF (via its N-terminus).
CC Interacts with the monomeric form of BIRC5/survivin deacetylated
CC at 'Lys-129'. Interacts with DTNBP1 and SERTAD2; the interactions
CC translocate DTNBP1 and SERTAD2 out of the nucleus. Interacts with
CC ATF2.
CC -!- INTERACTION:
CC O15392:BIRC5; NbExp=2; IntAct=EBI-355867, EBI-518823;
CC P04626:ERBB2; NbExp=2; IntAct=EBI-355867, EBI-641062;
CC P35232:PHB; NbExp=2; IntAct=EBI-355867, EBI-354213;
CC P61925:PKIA; NbExp=2; IntAct=EBI-355867, EBI-2682139;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleoplasm. Nucleus,
CC Cajal body. Nucleus, nucleolus. Note=Located in the nucleoplasm,
CC Cajal bodies and nucleoli. Shuttles between the nucleus/nucleolus
CC and the cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, placenta, lung,
CC liver, skeletal muscle, pancreas, spleen, thymus, prostate,
CC testis, ovary, small intestine, colon and peripheral blood
CC leukocytes. Not expressed in the kidney.
CC -!- MISCELLANEOUS: Cellular target of leptomycin B (LMB), a XPO1/CRM1
CC nuclear export inhibitor.
CC -!- SIMILARITY: Belongs to the exportin family.
CC -!- SIMILARITY: Contains 10 HEAT repeats.
CC -!- SIMILARITY: Contains 1 importin N-terminal domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/XPO1ID44168ch2p15.html";
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DR EMBL; Y08614; CAA69905.2; -; mRNA.
DR EMBL; D89729; BAA23415.1; -; mRNA.
DR EMBL; AK289920; BAF82609.1; -; mRNA.
DR EMBL; BX647758; CAH56174.1; -; mRNA.
DR EMBL; CR749840; CAH18695.1; -; mRNA.
DR EMBL; AC016727; AAY14949.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99993.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99994.1; -; Genomic_DNA.
DR EMBL; BC032847; AAH32847.1; -; mRNA.
DR RefSeq; NP_003391.1; NM_003400.3.
DR UniGene; Hs.370770; -.
DR PDB; 1W9C; X-ray; 2.30 A; A/B=707-1027.
DR PDB; 2L1L; NMR; -; B=504-630.
DR PDB; 3GB8; X-ray; 2.90 A; A=1-1071.
DR PDB; 4BSM; X-ray; 4.50 A; A=1-1032.
DR PDB; 4BSN; X-ray; 4.10 A; A=1-1032.
DR PDBsum; 1W9C; -.
DR PDBsum; 2L1L; -.
DR PDBsum; 3GB8; -.
DR PDBsum; 4BSM; -.
DR PDBsum; 4BSN; -.
DR ProteinModelPortal; O14980; -.
DR SMR; O14980; 53-1061.
DR DIP; DIP-33678N; -.
DR IntAct; O14980; 34.
DR MINT; MINT-5002192; -.
DR STRING; 9606.ENSP00000195419; -.
DR BindingDB; O14980; -.
DR ChEMBL; CHEMBL5661; -.
DR PhosphoSite; O14980; -.
DR PaxDb; O14980; -.
DR PRIDE; O14980; -.
DR DNASU; 7514; -.
DR Ensembl; ENST00000401558; ENSP00000384863; ENSG00000082898.
DR Ensembl; ENST00000404992; ENSP00000385942; ENSG00000082898.
DR Ensembl; ENST00000406957; ENSP00000385559; ENSG00000082898.
DR GeneID; 7514; -.
DR KEGG; hsa:7514; -.
DR UCSC; uc002sbh.3; human.
DR CTD; 7514; -.
DR GeneCards; GC02M061704; -.
DR HGNC; HGNC:12825; XPO1.
DR HPA; CAB010184; -.
DR MIM; 602559; gene.
DR neXtProt; NX_O14980; -.
DR PharmGKB; PA37418; -.
DR eggNOG; COG5101; -.
DR HOVERGEN; HBG052817; -.
DR InParanoid; O14980; -.
DR KO; K14290; -.
DR OMA; PQIGRIY; -.
DR OrthoDB; EOG7CZK4S; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR Reactome; REACT_71; Gene Expression.
DR SignaLink; O14980; -.
DR ChiTaRS; XPO1; human.
DR EvolutionaryTrace; O14980; -.
DR GeneWiki; XPO1; -.
DR GenomeRNAi; 7514; -.
DR NextBio; 29403; -.
DR PRO; PR:O14980; -.
DR ArrayExpress; O14980; -.
DR Bgee; O14980; -.
DR CleanEx; HS_XPO1; -.
DR Genevestigator; O14980; -.
DR GO; GO:0005642; C:annulate lamellae; IDA:UniProtKB.
DR GO; GO:0015030; C:Cajal body; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; TAS:ProtInc.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0030529; C:ribonucleoprotein complex; IDA:MGI.
DR GO; GO:0008565; F:protein transporter activity; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0005215; F:transporter activity; TAS:Reactome.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0075733; P:intracellular transport of virus; TAS:Reactome.
DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0016071; P:mRNA metabolic process; TAS:Reactome.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:Reactome.
DR GO; GO:0006611; P:protein export from nucleus; IEA:Ensembl.
DR GO; GO:0034504; P:protein localization to nucleus; IEA:Ensembl.
DR GO; GO:0010824; P:regulation of centrosome duplication; IEA:Ensembl.
DR GO; GO:0042176; P:regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0046825; P:regulation of protein export from nucleus; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome.
DR Gene3D; 1.25.10.10; -; 3.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR014877; CRM1_C_dom.
DR InterPro; IPR013598; Exportin-1/Importin-b-like.
DR InterPro; IPR001494; Importin-beta_N.
DR Pfam; PF08767; CRM1_C; 1.
DR Pfam; PF03810; IBN_N; 1.
DR Pfam; PF08389; Xpo1; 1.
DR SMART; SM01102; CRM1_C; 1.
DR SMART; SM00913; IBN_N; 1.
DR SUPFAM; SSF48371; SSF48371; 4.
DR PROSITE; PS50077; HEAT_REPEAT; FALSE_NEG.
DR PROSITE; PS50166; IMPORTIN_B_NT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Host-virus interaction; mRNA transport;
KW Nucleus; Phosphoprotein; Protein transport; Reference proteome;
KW Repeat; RNA-binding; Transport.
FT CHAIN 1 1071 Exportin-1.
FT /FTId=PRO_0000204705.
FT DOMAIN 46 112 Importin N-terminal.
FT REPEAT 217 240 HEAT 1.
FT REPEAT 241 277 HEAT 2.
FT REPEAT 354 472 HEAT 3.
FT REPEAT 515 553 HEAT 4.
FT REPEAT 560 597 HEAT 5.
FT REPEAT 602 639 HEAT 6.
FT REPEAT 775 813 HEAT 7.
FT REPEAT 885 916 HEAT 8.
FT REPEAT 917 954 HEAT 9.
FT REPEAT 1002 1039 HEAT 10.
FT REGION 1 679 Necessary for HTLV-1 Rex-mediated mRNA
FT export.
FT REGION 327 450 Interaction with Ran and nuclear export
FT complex formation.
FT REGION 411 481 Interaction with RANBP3.
FT REGION 411 414 Necessary for HTLV-1 Rex multimerization.
FT REGION 800 820 Interaction with HIV-1 Rev.
FT MOD_RES 391 391 Phosphoserine.
FT MOD_RES 446 446 N6-acetyllysine.
FT MOD_RES 448 448 Phosphothreonine (By similarity).
FT MOD_RES 450 450 Phosphoserine (By similarity).
FT MOD_RES 454 454 Phosphotyrosine (By similarity).
FT MOD_RES 693 693 N6-acetyllysine.
FT MUTAGEN 191 191 S->A: Does not abolish Rex-mediated mRNA
FT export.
FT MUTAGEN 284 284 V->E: Does not abolish Rex-mediated mRNA
FT export.
FT MUTAGEN 334 334 D->G: Does not abolish Rex-mediated mRNA
FT export.
FT MUTAGEN 337 337 I->L: Does not abolish Rex-mediated mRNA
FT export.
FT MUTAGEN 346 346 T->A: Does not abolish Rex-mediated mRNA
FT export.
FT MUTAGEN 402 402 V->I: Does not abolish Rex-mediated mRNA
FT export.
FT MUTAGEN 411 411 P->T: Strongly abolishes interaction with
FT Rex and RANBP3, abolishes Rex-mediated
FT mRNA export. Does not abolish interaction
FT with RANBP3; when associated with S-414.
FT Abolishes Rex multimerization; when
FT associated with S-414.
FT MUTAGEN 412 412 M->V: Does not abolish interaction with
FT Rex and RANBP3, and Rex-mediated mRNA
FT export.
FT MUTAGEN 414 414 F->S: Strongly abolishes interaction with
FT Rex and RANBP3, abolishes Rex-mediated
FT mRNA export. Does not abolish interaction
FT with RANBP3; when associated with T-411.
FT Abolishes Rex multimerization; when
FT associated with T-411.
FT MUTAGEN 428 447 EEVLVVENDQGEVVREFMKD->QQVLVVQNNQGQVVRQFMK
FT N: Abolishes Ran binding activity in
FT absence of cargo and abolishes partially
FT Ran binding activity in presence of
FT cargo.
FT MUTAGEN 430 446 VLVVENDQGEVVREFMK->DEDEENDQGEDEEEDDD:
FT Partially restores Ran binding activity
FT in presence of cargo.
FT MUTAGEN 430 433 VLVV->DEDE: Abolishes Ran binding
FT activity both in absence or presence of
FT cargo.
FT MUTAGEN 454 454 Y->A: Does not abolish Ran binding
FT activity and nuclear export complex
FT formation.
FT MUTAGEN 474 474 R->I: Strongly abolishes interaction with
FT Rex and RANBP3, abolishes Rex-mediated
FT mRNA export.
FT MUTAGEN 481 481 H->Q: Strongly abolishes interaction with
FT Rex and RANBP3, abolishes Rex-mediated
FT mRNA export.
FT MUTAGEN 513 513 E->A: Abolishes Ran binding activity and
FT nuclear export complex formation.
FT Abolishes Ran binding activity and
FT nuclear export complex formation; when
FT associated with A-553 and A-554.
FT MUTAGEN 525 525 L->A: Enhances Ran binding activity and
FT does not abolish nuclear export complex
FT formation. Does not abolish Ran binding
FT activity and partially abolish nuclear
FT export complex formation; when associated
FT with A-561. Does not abolish Ran binding
FT activity and partially abolish nuclear
FT export complex formation; when associated
FT with A-568 and A-572.
FT MUTAGEN 550 550 Q->A: Enhances Ran binding activity and
FT does not abolish nuclear export complex
FT formation; when associated with A-553 and
FT A-590.
FT MUTAGEN 553 553 R->A: Enhances Ran binding activity and
FT does not abolish nuclear export complex
FT formation; when associated with A-550 and
FT A-590. Abolishes Ran binding activity and
FT nuclear export complex formation; when
FT associated with A-513 and A-554.
FT MUTAGEN 554 554 F->A: Partially abolishes Ran binding
FT activity and does not abolish nuclear
FT export complex formation. Abolishes Ran
FT binding activity and nuclear export
FT complex formation; when associated with
FT A-561. Abolishes Ran binding activity and
FT nuclear export complex formation; when
FT associated with A-553 and A-513.
FT MUTAGEN 561 561 F->A: Abolishes Ran binding activity and
FT nuclear export complex formation.
FT Abolishes Ran binding activity and
FT nuclear export complex formation; when
FT associated with A-554. Does not abolish
FT Ran binding activity and partially
FT abolish nuclear export complex formation;
FT when associated with A-525.
FT MUTAGEN 568 568 K->A: Does not abolish Ran binding
FT activity and partially abolish nuclear
FT export complex formation; when associated
FT with A-525 and A-572.
FT MUTAGEN 572 572 F->A: Does not abolish Ran binding
FT activity and partially abolish nuclear
FT export complex formation; when associated
FT with A-525 and A-568.
FT MUTAGEN 583 583 M->A: Enhances Ran binding activity; when
FT associated with A-590.
FT MUTAGEN 590 590 K->A: Enhances Ran binding activity and
FT does not abolish nuclear export complex
FT formation. Enhances Ran binding activity
FT and does not abolish nuclear export
FT complex formation; when associated with
FT A-583. Enhances Ran binding activity and
FT does not abolish nuclear export complex
FT formation; when associated with A-550 and
FT A-553.
FT CONFLICT 406 406 R -> G (in Ref. 4; CAH56174).
FT CONFLICT 953 953 V -> G (in Ref. 4; CAH18695).
FT CONFLICT 989 989 L -> I (in Ref. 4; CAH56174).
FT HELIX 63 68
FT HELIX 76 89
FT HELIX 97 113
FT HELIX 124 141
FT TURN 142 145
FT HELIX 149 157
FT HELIX 161 175
FT HELIX 188 197
FT HELIX 199 215
FT HELIX 219 232
FT TURN 233 235
FT HELIX 238 242
FT STRAND 243 245
FT HELIX 246 253
FT TURN 254 256
FT HELIX 258 260
FT HELIX 261 273
FT HELIX 280 297
FT HELIX 304 310
FT HELIX 313 339
FT HELIX 341 343
FT HELIX 344 358
FT HELIX 363 383
FT HELIX 404 423
FT HELIX 448 467
FT HELIX 469 484
FT STRAND 485 488
FT HELIX 491 503
FT TURN 504 506
FT HELIX 510 530
FT HELIX 534 550
FT HELIX 552 557
FT HELIX 559 572
FT HELIX 580 595
FT HELIX 596 598
FT STRAND 605 608
FT HELIX 610 615
FT HELIX 618 622
FT HELIX 627 642
FT HELIX 647 674
FT HELIX 676 680
FT HELIX 682 702
FT HELIX 704 706
FT HELIX 711 713
FT HELIX 714 735
FT HELIX 738 741
FT HELIX 743 764
FT HELIX 769 775
FT HELIX 777 789
FT HELIX 793 795
FT HELIX 799 811
FT HELIX 812 818
FT HELIX 819 834
FT TURN 837 839
FT HELIX 842 858
FT HELIX 862 865
FT HELIX 868 881
FT STRAND 884 886
FT HELIX 887 906
FT HELIX 908 931
FT STRAND 932 934
FT HELIX 939 954
FT STRAND 964 966
FT HELIX 970 985
FT HELIX 991 1003
FT TURN 1004 1006
FT HELIX 1008 1023
FT TURN 1024 1026
FT TURN 1028 1030
FT HELIX 1031 1052
FT HELIX 1053 1055
SQ SEQUENCE 1071 AA; 123386 MW; FDB00C065DA2FB1D CRC64;
MPAIMTMLAD HAARQLLDFS QKLDINLLDN VVNCLYHGEG AQQRMAQEVL THLKEHPDAW
TRVDTILEFS QNMNTKYYGL QILENVIKTR WKILPRNQCE GIKKYVVGLI IKTSSDPTCV
EKEKVYIGKL NMILVQILKQ EWPKHWPTFI SDIVGASRTS ESLCQNNMVI LKLLSEEVFD
FSSGQITQVK SKHLKDSMCN EFSQIFQLCQ FVMENSQNAP LVHATLETLL RFLNWIPLGY
IFETKLISTL IYKFLNVPMF RNVSLKCLTE IAGVSVSQYE EQFVTLFTLT MMQLKQMLPL
NTNIRLAYSN GKDDEQNFIQ NLSLFLCTFL KEHDQLIEKR LNLRETLMEA LHYMLLVSEV
EETEIFKICL EYWNHLAAEL YRESPFSTSA SPLLSGSQHF DVPPRRQLYL PMLFKVRLLM
VSRMAKPEEV LVVENDQGEV VREFMKDTDS INLYKNMRET LVYLTHLDYV DTERIMTEKL
HNQVNGTEWS WKNLNTLCWA IGSISGAMHE EDEKRFLVTV IKDLLGLCEQ KRGKDNKAII
ASNIMYIVGQ YPRFLRAHWK FLKTVVNKLF EFMHETHDGV QDMACDTFIK IAQKCRRHFV
QVQVGEVMPF IDEILNNINT IICDLQPQQV HTFYEAVGYM IGAQTDQTVQ EHLIEKYMLL
PNQVWDSIIQ QATKNVDILK DPETVKQLGS ILKTNVRACK AVGHPFVIQL GRIYLDMLNV
YKCLSENISA AIQANGEMVT KQPLIRSMRT VKRETLKLIS GWVSRSNDPQ MVAENFVPPL
LDAVLIDYQR NVPAAREPEV LSTMAIIVNK LGGHITAEIP QIFDAVFECT LNMINKDFEE
YPEHRTNFFL LLQAVNSHCF PAFLAIPPTQ FKLVLDSIIW AFKHTMRNVA DTGLQILFTL
LQNVAQEEAA AQSFYQTYFC DILQHIFSVV TDTSHTAGLT MHASILAYMF NLVEEGKIST
SLNPGNPVNN QIFLQEYVAN LLKSAFPHLQ DAQVKLFVTG LFSLNQDIPA FKEHLRDFLV
QIKEFAGEDT SDLFLEEREI ALRQADEEKH KRQMSVPGIF NPHEIPEEMC D
//
MIM
602559
*RECORD*
*FIELD* NO
602559
*FIELD* TI
*602559 EXPORTIN 1; XPO1
;;REQUIRED FOR CHROMOSOME REGION MAINTENANCE; CRM1
*FIELD* TX
read more
CLONING
Human CRM1, or XPO1, is the homolog of yeast crm1 (named for 'required
for chromosome region maintenance'), a nuclear protein essential for
proliferation and chromosome region maintenance. Fornerod et al. (1997)
used the oncogenic nucleoporin CAN (114350) to coprecipitate human CRM1.
The complete cDNA encodes a predicted protein of 1,071 amino acids with
a predicted molecular mass of 123 kD. The CRM1 protein migrates at 112
kD. Human CRM1 has 47% identity with S. cerevisiae crm1 and 52% identity
with S. pombe crm1+. The N terminus of human CRM1 shares significant
homology with the N terminus of importin-beta. Fornerod et al. (1997)
identified a group of largely uncharacterized yeast and vertebrate
proteins of similar size (110 to 120 kD) that share this homology
domain, which they proposed to call the CRIME domain (for 'CRM1,
importin-beta, etc.').
Kudo et al. (1997) cloned human CRM1 cDNA using sequence information
from EST databases and a PCR-based strategy based on the sequence of S.
pombe crm1+. Northern blot analysis using the C-terminal region of human
CRM1 cDNA as a probe revealed a major transcript of 5.6 kb expressed in
all tissues tested except kidney.
GENE FUNCTION
Kudo et al. (1997) found that Human CRM1 weakly complemented the
cold-sensitive mutation of S. pombe crm1-809. Overproduction of human
CRM1 suppressed cell proliferation in wildtype S. pombe in an expression
level-dependent manner. Overexpression of native S. pombe crm1+ had the
same effect. Northern blot analysis with RNAs isolated from synchronized
mammalian cells showed that the expression of mammalian CRM1 was
initiated in the late G1 phase and reached a peak at G2/M, although the
protein level did not change during the cell cycle. Human CRM1 fused to
green fluorescent protein (GFP) and transiently expressed in NIH 3T3
cells showed that human CRM1 was localized preferentially in the nuclear
envelope, but was also detectable in the nucleoplasm and the cytoplasm.
A crm1 mutation of S. pombe caused nuclear import of a GFP fusion
protein containing a nuclear export signal (NES) but no change in the
distribution of a GFP fusion protein containing a nuclear localization
signal (NLS). These data suggested to Kudo et al. (1997) that CRM1 is a
novel cell cycle-regulated gene that is essential for the NES-dependent
nuclear export of proteins.
CRM1 protein binds CAN and NUP88 (602552), and its association with the
nuclear pore is dynamic (Fornerod et al., 1997). To test whether CRM1
could be a nuclear export receptor, Fornerod et al. (1997) used Xenopus
oocytes incubated in leptomycin B, a cytotoxin which blocks Rev export
and Rev-mediated RNA export in tissue culture cells. Leptomycin B
interacted directly with CRM1, as shown by gel shift assays, and blocked
export of Rev and U snRNAs from Xenopus oocyte nucleus. Overexpression
of CRM1 stimulated Rev and U snRNA export from the nucleus. Fornerod et
al. (1997) found that an NES/CRM1/Ran complex forms in the presence of
RanGTP. Leptomycin B blocks formation of this complex. Fornerod et al.
(1997) concluded that CRM1 is an export receptor for leucine-rich NESs.
Noting that CRM1 is a member of a family of proteins related to
importin-beta, Fornerod et al. (1997) suggested the descriptive name
'exportins' for those family members involved in nuclear export.
Stade et al. (1997) characterized CRM1 as an essential nuclear export
factor in S. cerevisiae and proposed that CRM1 be renamed 'exportin-1,'
symbolized XPO1. XPO1 protein is localized in the nucleus at steady
state but is capable of shuttling between the nucleus and cytoplasm.
Stade et al. (1997) constructed an NES-GFP-NLS substrate which shuttled
continuously between the nucleus and cytoplasm, but appeared largely
cytoplasmic, presumably due to a higher rate of export. In yeast
containing a temperature-sensitive mutation in CRM1, the substrate
became nuclear within 5 minutes at high temperature, indicating that the
mutation blocks NES export. High temperature also blocked mRNA export in
yeast. A 2-hybrid analysis showed an interaction between NES and CRM1
and between Ran and CRM1.
The cyclin-dependent kinase inhibitor p27(KIP1) (CDKN1B; 600778) is
degraded during the cell cycle by the ubiquitin-proteasome pathway.
Using NIH-3T3 mouse fibroblasts and mouse embryonic fibroblasts, Kamura
et al. (2004) found that a complex made up of Kpc1 (RNF123; 614472) and
Kpc2 (UBAC1; 608129) ubiquitinated cytoplasmic p27(KIP1) at G1 phase and
that cytoplasmic degradation of p27(KIP1) required p27(KIP1) nuclear
export by Crm1.
A single transcript in its unspliced and spliced forms directs synthesis
of all human immunodeficiency virus (HIV)-1 proteins. Although nuclear
export of intron-containing cellular transcripts is restricted in
mammalian cells, HIV-1 has evolved the viral Rev protein to overcome
this restriction for viral transcripts. CRM1 is a cellular cofactor for
Rev-dependent export of intron-containing HIV-1 RNA. Yedavalli et al.
(2004) presented evidence that Rev/CRM1 activity uses the ATP-dependent
RNA helicase DDX3 (300160). They showed that DDX3 is a nucleocytoplasmic
shuttling protein that binds CRM1 and localizes to nuclear membrane
pores. Knockdown of DDX3 using either antisense vector or
dominant-negative mutants suppressed Rev-RRE (Rev response element)
function in the export of incompletely spliced HIV-1 RNAs. Yedavalli et
al. (2004) concluded that DDX3 is the human RNA helicase that functions
in the CRM1 RNA export pathway analogously to the postulated role for
Dbp5 (605812) in yeast mRNA export.
For a review of nuclear export receptors, see Ullman et al. (1997).
BIOCHEMICAL FEATURES
- Crystal Structure
Dong et al. (2009) presented a 2.9-angstrom resolution crystal structure
of CRM1 bound to snurportin (SNUPN1; 607902). Snurportin-1 binds CRM1 in
a bipartite manner by means of an N-terminal leucine-rich nuclear export
signal (LR-NES) and its nucleotide-binding domain. The LR-NES is a
combined alpha-helical-extended structure that occupies a hydrophobic
groove between 2 CRM1 outer helices. The LR-NES interface explains the
consensus hydrophobic pattern, preference for intervening
electronegative residues, and inhibition by leptomycin B. The second
nuclear export signal epitope is a basic surface on the snurportin-1
nucleotide-binding domain, which binds an acidic patch on CRM1 adjacent
to the LR-NES site. Multipartite recognition of individually weak
nuclear export signal epitopes may be common to CRM1 substrates,
enhancing CRM1 binding beyond the generally low affinity LR-NES. Similar
energetic construction is also used in multipartite nuclear localization
signals to provide broad substrate specificity and rapid evolution in
nuclear transport.
Monecke et al. (2009) presented the crystal structure of the
SPN1-CRM1-RanGTP (see 601179) export complex at 2.5-angstrom resolution.
SPN1 is a nuclear import adapter for cytoplasmically assembled, m3G
(5-prime-2,2,7-terminal trimethylguanosine)-capped spliceosomal U
snRNPs. The structure showed how CRM1 can specifically return the
cargo-free form of SPN1 to the cytoplasm. The extensive contact area
includes 5 hydrophobic residues at the SPN1 amino terminus that dock
into a hydrophobic cleft of CRM1, as well as numerous hydrophilic
contacts of CRM1 to m3G cap-binding domain and carboxyl-terminal
residues of SPN1. Monecke et al. (2009) concluded that RanGTP promotes
cargo binding to CRM1 solely through long-range conformational changes
in the exportin.
MAPPING
The CRM1 gene maps to human chromosome 2p16 by fluorescence in situ
hybridization (Fornerod et al., 1997).
*FIELD* RF
1. Dong, X.; Biswas, A.; Suel, K. E.; Jackson, L. K.; Martinez, R.;
Gu, H.; Chook, Y. M.: Structural basis for leucine-rich nuclear export
signal recognition by CRM1. Nature 458: 1136-1141, 2009. Note: Erratum:
Nature 461: 550 only, 2009.
2. Fornerod, M.; Ohno, M.; Yoshida, M.; Mattaj, I. W.: CRM1 is an
export receptor for leucine-rich nuclear export signals. Cell 90:
1051-1060, 1997.
3. Fornerod, M.; van Baal, S.; Valentine, V.; Shapiro, D. N.; Grosveld,
G.: Chromosomal localization of genes encoding CAN/Nup214-interacting
proteins--human CRM1 localizes to 2p16, whereas Nup88 localizes to
17p13 and is physically linked to SF2p32. Genomics 42: 538-540,
1997.
4. Fornerod, M.; van Duersen, J.; van Baal, S.; Reynolds, A.; Davis,
D.; Murti, K. G.; Fransen, J.; Grosveld, G.: The human homologue
of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel
nuclear pore component Nup88. EMBO J. 16: 807-816, 1997.
5. Kamura, T.; Hara, T.; Matsumoto, M.; Ishida, N.; Okumura, F.; Hatakeyama,
S.; Yoshida, M.; Nakayama, K.; Nakayama, K. I.: Cytoplasmic ubiquitin
ligase KPC regulates proteolysis of p27(Kip1) at G1 phase. Nature
Cell Biol. 6: 1229-1235, 2004.
6. Kudo, N.; Khochbin, S.; Nishi, K.; Kitano, K.; Yanagida, M.; Yoshida,
M.; Horinouchi, S.: Molecular cloning and cell cycle-dependent expression
of mammalian CRM1, a protein involved in nuclear export of proteins. J.
Biol. Chem. 272: 29742-29751, 1997.
7. Monecke, T.; Guttler, T.; Neumann, P.; Dickmanns, A.; Gorlich,
D.; Ficner, R.: Crystal structure of the nuclear export receptor
CRM1 in complex with snurportin 1 and RanGTP. Science 324: 1087-1091,
2009.
8. Stade, K.; Ford, C. S.; Guthrie, C.; Weis, K.: Exportin 1 (Crm1p)
is an essential nuclear export factor. Cell 90: 1041-1050, 1997.
9. Ullman, K. S.; Powers, M. A.; Forbes, D. J.: Nuclear export receptors:
from importin to exportin. Cell 90: 967-970, 1997.
10. Yedavalli, V. S. R. K.; Neuveut, C.; Chi, Y.; Kleiman, L.; Jeang,
K.-T.: Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE
export function. Cell 119: 381-392, 2004.
*FIELD* CN
Patricia A. Hartz - updated: 10/24/2011
Ada Hamosh - updated: 10/19/2009
Ada Hamosh - updated: 6/17/2009
Ada Hamosh - updated: 5/12/2009
Stylianos E. Antonarakis - updated: 1/19/2005
*FIELD* CD
Ada Hamosh: 4/24/1998
*FIELD* ED
mgross: 02/06/2012
terry: 10/24/2011
terry: 10/19/2009
alopez: 6/23/2009
terry: 6/17/2009
alopez: 5/12/2009
terry: 5/12/2009
wwang: 6/3/2008
terry: 5/30/2008
mgross: 1/19/2005
alopez: 5/11/1998
alopez: 4/24/1998
*RECORD*
*FIELD* NO
602559
*FIELD* TI
*602559 EXPORTIN 1; XPO1
;;REQUIRED FOR CHROMOSOME REGION MAINTENANCE; CRM1
*FIELD* TX
read more
CLONING
Human CRM1, or XPO1, is the homolog of yeast crm1 (named for 'required
for chromosome region maintenance'), a nuclear protein essential for
proliferation and chromosome region maintenance. Fornerod et al. (1997)
used the oncogenic nucleoporin CAN (114350) to coprecipitate human CRM1.
The complete cDNA encodes a predicted protein of 1,071 amino acids with
a predicted molecular mass of 123 kD. The CRM1 protein migrates at 112
kD. Human CRM1 has 47% identity with S. cerevisiae crm1 and 52% identity
with S. pombe crm1+. The N terminus of human CRM1 shares significant
homology with the N terminus of importin-beta. Fornerod et al. (1997)
identified a group of largely uncharacterized yeast and vertebrate
proteins of similar size (110 to 120 kD) that share this homology
domain, which they proposed to call the CRIME domain (for 'CRM1,
importin-beta, etc.').
Kudo et al. (1997) cloned human CRM1 cDNA using sequence information
from EST databases and a PCR-based strategy based on the sequence of S.
pombe crm1+. Northern blot analysis using the C-terminal region of human
CRM1 cDNA as a probe revealed a major transcript of 5.6 kb expressed in
all tissues tested except kidney.
GENE FUNCTION
Kudo et al. (1997) found that Human CRM1 weakly complemented the
cold-sensitive mutation of S. pombe crm1-809. Overproduction of human
CRM1 suppressed cell proliferation in wildtype S. pombe in an expression
level-dependent manner. Overexpression of native S. pombe crm1+ had the
same effect. Northern blot analysis with RNAs isolated from synchronized
mammalian cells showed that the expression of mammalian CRM1 was
initiated in the late G1 phase and reached a peak at G2/M, although the
protein level did not change during the cell cycle. Human CRM1 fused to
green fluorescent protein (GFP) and transiently expressed in NIH 3T3
cells showed that human CRM1 was localized preferentially in the nuclear
envelope, but was also detectable in the nucleoplasm and the cytoplasm.
A crm1 mutation of S. pombe caused nuclear import of a GFP fusion
protein containing a nuclear export signal (NES) but no change in the
distribution of a GFP fusion protein containing a nuclear localization
signal (NLS). These data suggested to Kudo et al. (1997) that CRM1 is a
novel cell cycle-regulated gene that is essential for the NES-dependent
nuclear export of proteins.
CRM1 protein binds CAN and NUP88 (602552), and its association with the
nuclear pore is dynamic (Fornerod et al., 1997). To test whether CRM1
could be a nuclear export receptor, Fornerod et al. (1997) used Xenopus
oocytes incubated in leptomycin B, a cytotoxin which blocks Rev export
and Rev-mediated RNA export in tissue culture cells. Leptomycin B
interacted directly with CRM1, as shown by gel shift assays, and blocked
export of Rev and U snRNAs from Xenopus oocyte nucleus. Overexpression
of CRM1 stimulated Rev and U snRNA export from the nucleus. Fornerod et
al. (1997) found that an NES/CRM1/Ran complex forms in the presence of
RanGTP. Leptomycin B blocks formation of this complex. Fornerod et al.
(1997) concluded that CRM1 is an export receptor for leucine-rich NESs.
Noting that CRM1 is a member of a family of proteins related to
importin-beta, Fornerod et al. (1997) suggested the descriptive name
'exportins' for those family members involved in nuclear export.
Stade et al. (1997) characterized CRM1 as an essential nuclear export
factor in S. cerevisiae and proposed that CRM1 be renamed 'exportin-1,'
symbolized XPO1. XPO1 protein is localized in the nucleus at steady
state but is capable of shuttling between the nucleus and cytoplasm.
Stade et al. (1997) constructed an NES-GFP-NLS substrate which shuttled
continuously between the nucleus and cytoplasm, but appeared largely
cytoplasmic, presumably due to a higher rate of export. In yeast
containing a temperature-sensitive mutation in CRM1, the substrate
became nuclear within 5 minutes at high temperature, indicating that the
mutation blocks NES export. High temperature also blocked mRNA export in
yeast. A 2-hybrid analysis showed an interaction between NES and CRM1
and between Ran and CRM1.
The cyclin-dependent kinase inhibitor p27(KIP1) (CDKN1B; 600778) is
degraded during the cell cycle by the ubiquitin-proteasome pathway.
Using NIH-3T3 mouse fibroblasts and mouse embryonic fibroblasts, Kamura
et al. (2004) found that a complex made up of Kpc1 (RNF123; 614472) and
Kpc2 (UBAC1; 608129) ubiquitinated cytoplasmic p27(KIP1) at G1 phase and
that cytoplasmic degradation of p27(KIP1) required p27(KIP1) nuclear
export by Crm1.
A single transcript in its unspliced and spliced forms directs synthesis
of all human immunodeficiency virus (HIV)-1 proteins. Although nuclear
export of intron-containing cellular transcripts is restricted in
mammalian cells, HIV-1 has evolved the viral Rev protein to overcome
this restriction for viral transcripts. CRM1 is a cellular cofactor for
Rev-dependent export of intron-containing HIV-1 RNA. Yedavalli et al.
(2004) presented evidence that Rev/CRM1 activity uses the ATP-dependent
RNA helicase DDX3 (300160). They showed that DDX3 is a nucleocytoplasmic
shuttling protein that binds CRM1 and localizes to nuclear membrane
pores. Knockdown of DDX3 using either antisense vector or
dominant-negative mutants suppressed Rev-RRE (Rev response element)
function in the export of incompletely spliced HIV-1 RNAs. Yedavalli et
al. (2004) concluded that DDX3 is the human RNA helicase that functions
in the CRM1 RNA export pathway analogously to the postulated role for
Dbp5 (605812) in yeast mRNA export.
For a review of nuclear export receptors, see Ullman et al. (1997).
BIOCHEMICAL FEATURES
- Crystal Structure
Dong et al. (2009) presented a 2.9-angstrom resolution crystal structure
of CRM1 bound to snurportin (SNUPN1; 607902). Snurportin-1 binds CRM1 in
a bipartite manner by means of an N-terminal leucine-rich nuclear export
signal (LR-NES) and its nucleotide-binding domain. The LR-NES is a
combined alpha-helical-extended structure that occupies a hydrophobic
groove between 2 CRM1 outer helices. The LR-NES interface explains the
consensus hydrophobic pattern, preference for intervening
electronegative residues, and inhibition by leptomycin B. The second
nuclear export signal epitope is a basic surface on the snurportin-1
nucleotide-binding domain, which binds an acidic patch on CRM1 adjacent
to the LR-NES site. Multipartite recognition of individually weak
nuclear export signal epitopes may be common to CRM1 substrates,
enhancing CRM1 binding beyond the generally low affinity LR-NES. Similar
energetic construction is also used in multipartite nuclear localization
signals to provide broad substrate specificity and rapid evolution in
nuclear transport.
Monecke et al. (2009) presented the crystal structure of the
SPN1-CRM1-RanGTP (see 601179) export complex at 2.5-angstrom resolution.
SPN1 is a nuclear import adapter for cytoplasmically assembled, m3G
(5-prime-2,2,7-terminal trimethylguanosine)-capped spliceosomal U
snRNPs. The structure showed how CRM1 can specifically return the
cargo-free form of SPN1 to the cytoplasm. The extensive contact area
includes 5 hydrophobic residues at the SPN1 amino terminus that dock
into a hydrophobic cleft of CRM1, as well as numerous hydrophilic
contacts of CRM1 to m3G cap-binding domain and carboxyl-terminal
residues of SPN1. Monecke et al. (2009) concluded that RanGTP promotes
cargo binding to CRM1 solely through long-range conformational changes
in the exportin.
MAPPING
The CRM1 gene maps to human chromosome 2p16 by fluorescence in situ
hybridization (Fornerod et al., 1997).
*FIELD* RF
1. Dong, X.; Biswas, A.; Suel, K. E.; Jackson, L. K.; Martinez, R.;
Gu, H.; Chook, Y. M.: Structural basis for leucine-rich nuclear export
signal recognition by CRM1. Nature 458: 1136-1141, 2009. Note: Erratum:
Nature 461: 550 only, 2009.
2. Fornerod, M.; Ohno, M.; Yoshida, M.; Mattaj, I. W.: CRM1 is an
export receptor for leucine-rich nuclear export signals. Cell 90:
1051-1060, 1997.
3. Fornerod, M.; van Baal, S.; Valentine, V.; Shapiro, D. N.; Grosveld,
G.: Chromosomal localization of genes encoding CAN/Nup214-interacting
proteins--human CRM1 localizes to 2p16, whereas Nup88 localizes to
17p13 and is physically linked to SF2p32. Genomics 42: 538-540,
1997.
4. Fornerod, M.; van Duersen, J.; van Baal, S.; Reynolds, A.; Davis,
D.; Murti, K. G.; Fransen, J.; Grosveld, G.: The human homologue
of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel
nuclear pore component Nup88. EMBO J. 16: 807-816, 1997.
5. Kamura, T.; Hara, T.; Matsumoto, M.; Ishida, N.; Okumura, F.; Hatakeyama,
S.; Yoshida, M.; Nakayama, K.; Nakayama, K. I.: Cytoplasmic ubiquitin
ligase KPC regulates proteolysis of p27(Kip1) at G1 phase. Nature
Cell Biol. 6: 1229-1235, 2004.
6. Kudo, N.; Khochbin, S.; Nishi, K.; Kitano, K.; Yanagida, M.; Yoshida,
M.; Horinouchi, S.: Molecular cloning and cell cycle-dependent expression
of mammalian CRM1, a protein involved in nuclear export of proteins. J.
Biol. Chem. 272: 29742-29751, 1997.
7. Monecke, T.; Guttler, T.; Neumann, P.; Dickmanns, A.; Gorlich,
D.; Ficner, R.: Crystal structure of the nuclear export receptor
CRM1 in complex with snurportin 1 and RanGTP. Science 324: 1087-1091,
2009.
8. Stade, K.; Ford, C. S.; Guthrie, C.; Weis, K.: Exportin 1 (Crm1p)
is an essential nuclear export factor. Cell 90: 1041-1050, 1997.
9. Ullman, K. S.; Powers, M. A.; Forbes, D. J.: Nuclear export receptors:
from importin to exportin. Cell 90: 967-970, 1997.
10. Yedavalli, V. S. R. K.; Neuveut, C.; Chi, Y.; Kleiman, L.; Jeang,
K.-T.: Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE
export function. Cell 119: 381-392, 2004.
*FIELD* CN
Patricia A. Hartz - updated: 10/24/2011
Ada Hamosh - updated: 10/19/2009
Ada Hamosh - updated: 6/17/2009
Ada Hamosh - updated: 5/12/2009
Stylianos E. Antonarakis - updated: 1/19/2005
*FIELD* CD
Ada Hamosh: 4/24/1998
*FIELD* ED
mgross: 02/06/2012
terry: 10/24/2011
terry: 10/19/2009
alopez: 6/23/2009
terry: 6/17/2009
alopez: 5/12/2009
terry: 5/12/2009
wwang: 6/3/2008
terry: 5/30/2008
mgross: 1/19/2005
alopez: 5/11/1998
alopez: 4/24/1998