XPO1_DROME
ID XPO1_DROME Reviewed; 1063 AA.
AC Q9TVM2; Q9I7N7; Q9U699;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Exportin-1;
DE AltName: Full=Chromosome region maintenance 1 protein;
DE AltName: Full=Protein embargoed;
GN Name=emb {ECO:0000312|FlyBase:FBgn0020497};
GN Synonyms=Crm1 {ECO:0000312|EMBL:CAB53566.1}; ORFNames=CG13387;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAD55778.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, INTERACTION WITH ACTIN,
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=Oregon-R {ECO:0000269|PubMed:10924475};
RC TISSUE=Embryo {ECO:0000269|PubMed:10924475};
RX PubMed=10924475; DOI=10.1093/genetics/155.4.1799;
RA Collier S., Chan H.Y.E., Toda T., McKimmie C., Johnson G., Adler P.N.,
RA O'Kane C., Ashburner M.;
RT "The Drosophila embargoed gene is required for larval progression and
RT encodes the functional homolog of Schizosaccharomyces Crm1.";
RL Genetics 155:1799-1807(2000).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAF01341.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10636888; DOI=10.1074/jbc.275.3.1878;
RA Fasken M.B., Saunders R., Rosenberg M., Brighty D.W.;
RT "A leptomycin B-sensitive homologue of human CRM1 promotes nuclear export
RT of nuclear export sequence-containing proteins in Drosophila cells.";
RL J. Biol. Chem. 275:1878-1886(2000).
RN [3] {ECO:0000312|EMBL:CAB53566.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hovemann B.T., Heiermann R., Malz J., Richardt A., Stoertkuhl K.F.,
RA Sehlmeyer F.;
RT "Delineation of a modular structered enhancer that gives rise to olfactory
RT organ specific expression of Drosophila1-acylglycerol-3-phosphate O-
RT acyltransferase.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000312|EMBL:AAG22423.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAG22423.2}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [6] {ECO:0000312|EMBL:AAL90296.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL90296.1};
RC TISSUE=Embryo {ECO:0000269|PubMed:12537569};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [7] {ECO:0000305}
RP FUNCTION, ASSOCIATION WITH NUCLEAR PORE COMPLEX, INTERACTION WITH MBO,
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF MET-412 AND
RP 487-ASN--GLU-1063.
RX PubMed=14638854; DOI=10.1083/jcb.200304046;
RA Roth P., Xylourgidis N., Sabri N., Uv A.E., Fornerod M., Samakovlis C.;
RT "The Drosophila nucleoporin DNup88 localizes DNup214 and CRM1 on the
RT nuclear envelope and attenuates NES-mediated nuclear export.";
RL J. Cell Biol. 163:701-706(2003).
RN [8]
RP FUNCTION, AND INTERACTION WITH CLBN.
RX PubMed=16103875; DOI=10.1038/sj.onc.1208962;
RA Bi X., Jones T., Abbasi F., Lee H., Stultz B., Hursh D.A., Mortin M.A.;
RT "Drosophila caliban, a nuclear export mediator, can function as a tumor
RT suppressor in human lung cancer cells.";
RL Oncogene 24:8229-8239(2005).
RN [9]
RP FUNCTION, ASSOCIATION WITH NUCLEAR PORE COMPLEX, INTERACTION WITH NUP214
RP AND MBO, SUBCELLULAR LOCATION, AND MUTAGENESIS OF MET-412 AND
RP 487-ASN--GLU-1063.
RX PubMed=17032737; DOI=10.1242/jcs.03201;
RA Xylourgidis N., Roth P., Sabri N., Tsarouhas V., Samakovlis C.;
RT "The nucleoporin Nup214 sequesters CRM1 at the nuclear rim and modulates
RT NFkappaB activation in Drosophila.";
RL J. Cell Sci. 119:4409-4419(2006).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25858587; DOI=10.1074/jbc.m114.607036;
RA Kim W., Kim H.D., Jung Y., Kim J., Chung J.;
RT "Drosophila Low Temperature Viability Protein 1 (LTV1) Is Required for
RT Ribosome Biogenesis and Cell Growth Downstream of Drosophila Myc (dMyc).";
RL J. Biol. Chem. 290:13591-13604(2015).
RN [11]
RP FUNCTION.
RX PubMed=31626769; DOI=10.1016/j.cell.2019.09.022;
RA Hampoelz B., Schwarz A., Ronchi P., Bragulat-Teixidor H., Tischer C.,
RA Gaspar I., Ephrussi A., Schwab Y., Beck M.;
RT "Nuclear Pores Assemble from Nucleoporin Condensates During Oogenesis.";
RL Cell 179:671-686.E17(2019).
CC -!- FUNCTION: Receptor for the leucine-rich nuclear export signal (NES)
CC (PubMed:10636888, PubMed:14638854, PubMed:16103875). Binds
CC cooperatively to the NES on its target protein and to the small GTPase
CC Ran in its active GTP-bound form (PubMed:10636888, PubMed:14638854).
CC Involved in the export of dl, RpS2 and the pre-40S ribosome from the
CC nucleus to the cytoplasm (PubMed:14638854, PubMed:25858587,
CC PubMed:17032737). Plays an important role in nuclear pore assembly by
CC mediating nucleoporin condensation and biogenesis of annulate lamellae
CC (PubMed:31626769). Required for the function or maintenance of certain
CC tissues such as brain and gut (PubMed:10924475).
CC {ECO:0000269|PubMed:10636888, ECO:0000269|PubMed:10924475,
CC ECO:0000269|PubMed:14638854, ECO:0000269|PubMed:17032737,
CC ECO:0000269|PubMed:25858587, ECO:0000269|PubMed:31626769}.
CC -!- SUBUNIT: Interacts with Clbn (via its N-terminus) (PubMed:16103875).
CC Associates with the nuclear pore complex via interaction with mbo and
CC Nup214 (PubMed:14638854, PubMed:17032737). Interacts with target
CC proteins containing NES sequences such as actin and dl
CC (PubMed:10924475, PubMed:14638854, PubMed:17032737).
CC {ECO:0000269|PubMed:10924475, ECO:0000269|PubMed:14638854,
CC ECO:0000269|PubMed:16103875, ECO:0000269|PubMed:17032737}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17032737}. Nucleus
CC membrane {ECO:0000269|PubMed:17032737}; Peripheral membrane protein;
CC Nucleoplasmic side. Note=Localization to the nuclear pore complex is
CC promoted by Nup214. {ECO:0000269|PubMed:17032737}.
CC -!- TISSUE SPECIFICITY: High expression observed in the developing
CC embryonic brain, hind gut and posterior spiracles shortly before dorsal
CC closure; and in the ventral nerve cord, midgut and somatic musculature
CC shortly after dorsal closure. Expression increases when the tissue is
CC well developed. {ECO:0000269|PubMed:10924475}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the larva (at protein level)
CC (PubMed:14638854). Highly expressed both maternally and zygotically
CC (PubMed:10924475). {ECO:0000269|PubMed:10924475,
CC ECO:0000269|PubMed:14638854}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in defects in
CC nuclear export resulting in accumulation of RpS2 and pre-40S ribosome
CC in the nucleus (PubMed:25858587). During oogenesis, mislocalizes
CC Nup358-containing granules to nurse cells and abolishes the formation
CC of annulate lamellae (PubMed:31626769). {ECO:0000269|PubMed:25858587,
CC ECO:0000269|PubMed:31626769}.
CC -!- MISCELLANEOUS: Activity inhibited by leptomycin B, which disrupts
CC interaction with the NES and RanGTP. {ECO:0000269|PubMed:10636888}.
CC -!- SIMILARITY: Belongs to the exportin family. {ECO:0000255}.
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DR EMBL; AF179360; AAD55778.1; -; mRNA.
DR EMBL; AF179361; AAD55780.1; -; Genomic_DNA.
DR EMBL; AF190557; AAF01341.1; -; mRNA.
DR EMBL; AJ249178; CAB53566.1; -; mRNA.
DR EMBL; AE014134; AAG22423.2; -; Genomic_DNA.
DR EMBL; AY089558; AAL90296.1; -; mRNA.
DR RefSeq; NP_001303316.1; NM_001316387.1.
DR RefSeq; NP_723391.2; NM_164818.2.
DR AlphaFoldDB; Q9TVM2; -.
DR SMR; Q9TVM2; -.
DR BioGRID; 60290; 17.
DR DIP; DIP-21235N; -.
DR IntAct; Q9TVM2; 12.
DR MINT; Q9TVM2; -.
DR STRING; 7227.FBpp0079278; -.
DR PaxDb; Q9TVM2; -.
DR PRIDE; Q9TVM2; -.
DR DNASU; 34167; -.
DR EnsemblMetazoa; FBtr0079663; FBpp0079278; FBgn0020497.
DR EnsemblMetazoa; FBtr0346708; FBpp0312321; FBgn0020497.
DR GeneID; 34167; -.
DR KEGG; dme:Dmel_CG13387; -.
DR CTD; 133418; -.
DR FlyBase; FBgn0020497; emb.
DR VEuPathDB; VectorBase:FBgn0020497; -.
DR eggNOG; KOG2020; Eukaryota.
DR GeneTree; ENSGT00940000153408; -.
DR HOGENOM; CLU_011906_0_0_1; -.
DR InParanoid; Q9TVM2; -.
DR OMA; HNINTLC; -.
DR OrthoDB; 132850at2759; -.
DR PhylomeDB; Q9TVM2; -.
DR Reactome; R-DME-3769402; Deactivation of the beta-catenin transactivating complex.
DR Reactome; R-DME-450520; HuR (ELAVL1) binds and stabilizes mRNA.
DR Reactome; R-DME-69273; Cyclin A/B1/B2 associated events during G2/M transition.
DR Reactome; R-DME-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR Reactome; R-DME-9707616; Heme signaling.
DR SignaLink; Q9TVM2; -.
DR BioGRID-ORCS; 34167; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 34167; -.
DR PRO; PR:Q9TVM2; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0020497; Expressed in wing disc and 42 other tissues.
DR ExpressionAtlas; Q9TVM2; baseline and differential.
DR Genevisible; Q9TVM2; DM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031965; C:nuclear membrane; IDA:FlyBase.
DR GO; GO:0005643; C:nuclear pore; IMP:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0005049; F:nuclear export signal receptor activity; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR GO; GO:0007099; P:centriole replication; IMP:FlyBase.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0051168; P:nuclear export; IDA:FlyBase.
DR GO; GO:0051292; P:nuclear pore complex assembly; IMP:UniProtKB.
DR GO; GO:0006611; P:protein export from nucleus; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IDA:UniProtKB.
DR GO; GO:1900037; P:regulation of cellular response to hypoxia; IMP:FlyBase.
DR GO; GO:0000055; P:ribosomal large subunit export from nucleus; IBA:GO_Central.
DR GO; GO:0000056; P:ribosomal small subunit export from nucleus; IMP:FlyBase.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR041123; CRM1_repeat.
DR InterPro; IPR041235; Exp1_repeat_2.
DR InterPro; IPR013598; Exportin-1/Importin-b-like.
DR InterPro; IPR001494; Importin-beta_N.
DR InterPro; IPR045065; XPO1/5.
DR InterPro; IPR014877; XPO1_C_dom.
DR InterPro; IPR040485; XPO1_repeat_3.
DR PANTHER; PTHR11223; PTHR11223; 1.
DR Pfam; PF08767; CRM1_C; 1.
DR Pfam; PF18777; CRM1_repeat; 1.
DR Pfam; PF18784; CRM1_repeat_2; 1.
DR Pfam; PF18787; CRM1_repeat_3; 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; 1.
DR PROSITE; PS50166; IMPORTIN_B_NT; 1.
PE 1: Evidence at protein level;
KW Membrane; mRNA transport; Nucleus; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1..1063
FT /note="Exportin-1"
FT /id="PRO_0000204708"
FT DOMAIN 43..109
FT /note="Importin N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00115"
FT REGION 1034..1063
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 412
FT /note="M->R: Results in lethality at larval stage. This is
FT reversed by removal of one chromosome copy of Nup214. Fails
FT to export proteins containing leucine-rich nuclear export
FT signal (NES) from the nucleus."
FT /evidence="ECO:0000269|PubMed:14638854,
FT ECO:0000269|PubMed:17032737"
FT MUTAGEN 487..1063
FT /note="Missing: Fails to export proteins containing
FT leucine-rich nuclear export signal (NES) from the nucleus."
FT /evidence="ECO:0000269|PubMed:14638854,
FT ECO:0000269|PubMed:17032737"
FT CONFLICT 1017
FT /note="T -> A (in Ref. 2; AAF01341)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1063 AA; 122799 MW; BBE2FF53859BD1FE CRC64;
MATMLTSDEA GKLLDFSQKL DINLLDKIVE VVYTAQGEQL RLAQSILTTL KEHPEAWTRV
DSILEYSQNQ RTKFYALQIL EEVIKTRWKV LPRNQCEGIK KYVVSLIIKT SSDPIVMEQN
KVYLNKLNMI LVHILKREWP RNWETFISDI VGASKTNESL CMNNMVILKN LSEEVFDFSQ
GQITQTKAKH LKDTMCSEFS QIFTLCSFVL ENSMNAALIH VTLETLLRFL NWIPLGYIFE
TQQIETLIFK FLSVPMFRNV TLKCLSEIAG LTAANYDENF ATLFKDTMVQ LEQIVGQNMN
MNHVFKHGSD TEQELVLNLA MFLCTFLKEH GKLVEDAKYV DYLNQALMYL VMISEVEDVE
VFKICLEYWN SLVEDLYNSE FFHPTLESTK RQQVYPRRRF YAPILSKVRF IMISRMAKPE
EVLVVENENG EVVREFMKDT NSINLYKNMR ETLVFLTHLD SVDTDRIMTL KLLNQVNGSE
FSWKNLNTLC WAIGSISGAF CEEDEKRFLV TVIKDLLGLC EQKKGKDNKA IIASNIMYVV
GQYPRFLRAH WKFLKTVVNK LFEFMHETHD GVQDMACDTF IKIAIKCRRY FVTIQPNEAC
TFIDEILTTM SSIICDLQPQ QVHTFYEAVG YMISAQVDQV QQDVLIERYM QLPNQVWDDI
ISRASKNVDF LKNMTAVKQL GSILKTNVAA CKALGHAYVI QLGRIYLDML NVYKITSENI
IQAIEVNGVN VNNQPLIKTM HVVKKETLNL ISEWVSRSND NQLVMDNFIP PLLDAILLDY
QRCKVPSARE PKVLSAMAII VHKLRQHITN EVPKIFDAVF ECTLDMINKN FEDFPQHRLS
FYELLQAVNA HCFKAFLNIP PAQFKLVFDS VVWAFKHTMR NVADMGLNIL FKMLQNLDQH
PGAAQSFYQT YFTDILMQIF SVVTDTSHTA GLPNHAIILA YMFSLVENRK ITVNLGPIPD
NMIFIQEYVA SLLKSAFTHL SDNQVKVFVT GLFNLDENVQ AFKEHLRDFL IQIREATGED
DSDLYLEERE AALAEEQSNK HQMQRNIPGM LNPHELPEDM QDE
