XPO4_MOUSE
ID XPO4_MOUSE Reviewed; 1151 AA.
AC Q9ESJ0; E9QLH3; Q6ZPJ4;
DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Exportin-4 {ECO:0000303|PubMed:10944119};
DE Short=Exp4 {ECO:0000303|PubMed:10944119};
GN Name=Xpo4 {ECO:0000303|PubMed:27306458, ECO:0000312|MGI:MGI:1888526};
GN Synonyms=Kiaa1721 {ECO:0000303|PubMed:14621295};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10944119; DOI=10.1093/emboj/19.16.4362;
RA Lipowsky G., Bischoff F.R., Schwarzmaier P., Kraft R., Kostka S.,
RA Hartmann E., Kutay U., Goerlich D.;
RT "Exportin 4: a mediator of a novel nuclear export pathway in higher
RT eukaryotes.";
RL EMBO J. 19:4362-4371(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-1151.
RC TISSUE=Embryonic tail;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [4]
RP FUNCTION.
RX PubMed=19349578; DOI=10.1083/jcb.200810106;
RA Gontan C., Guettler T., Engelen E., Demmers J., Fornerod M., Grosveld F.G.,
RA Tibboel D., Goerlich D., Poot R.A., Rottier R.J.;
RT "Exportin 4 mediates a novel nuclear import pathway for Sox family
RT transcription factors.";
RL J. Cell Biol. 185:27-34(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-464 AND SER-521, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6] {ECO:0007744|PDB:5DLQ}
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) IN COMPLEX WITH EIF5A AND RAN, AND
RP MUTAGENESIS OF GLU-462; GLU-465; ASP-470; GLU-537; SER-631 AND SER-695.
RX PubMed=27306458; DOI=10.1038/ncomms11952;
RA Aksu M., Trakhanov S., Goerlich D.;
RT "Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-
RT containing translation factor eIF5A.";
RL Nat. Commun. 7:11952-11952(2016).
CC -!- FUNCTION: Mediates the nuclear export of proteins (cargos), such as
CC EIF5A, SMAD3 and isoform M2 of PKM (PKM2) (By similarity). In the
CC nucleus binds cooperatively to its cargo and to the GTPase Ran in its
CC active GTP-bound form (By similarity). Docking of this trimeric complex
CC to the nuclear pore complex (NPC) is mediated through binding to
CC nucleoporins (By similarity). Upon transit of a nuclear export complex
CC into the cytoplasm, disassembling of the complex and hydrolysis of Ran-
CC GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause
CC release of the cargo from the export receptor (By similarity). XPO4
CC then return to the nuclear compartment and mediate another round of
CC transport (By similarity). The directionality of nuclear export is
CC thought to be conferred by an asymmetric distribution of the GTP- and
CC GDP-bound forms of Ran between the cytoplasm and nucleus (By
CC similarity). Catalyzes the nuclear export of hypusinated EIF5A; a small
CC cytoplasmic protein that enters nucleus and accumulates within
CC nucleolus if not exported back by XPO4 (PubMed:27306458). Specifically
CC mediates nuclear export of isoform M2 of PKM (PKM2) following PKM2
CC deacetylation by SIRT6 (By similarity). Also mediates the nuclear
CC import of SOX transcription factors SRY and SOX2 (PubMed:19349578).
CC {ECO:0000250|UniProtKB:Q9C0E2, ECO:0000269|PubMed:19349578,
CC ECO:0000269|PubMed:27306458}.
CC -!- SUBUNIT: Interacts with Ran and cargo proteins in a GTP-dependent
CC manner. {ECO:0000269|PubMed:27306458}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9C0E2}. Nucleus
CC {ECO:0000250|UniProtKB:Q9C0E2}. Note=Shuttles between the nucleus and
CC the cytoplasm. {ECO:0000250|UniProtKB:Q9C0E2}.
CC -!- SIMILARITY: Belongs to the exportin family. {ECO:0000305}.
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DR EMBL; AF145021; AAG09133.1; -; mRNA.
DR EMBL; AC154504; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC154675; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK129430; BAC98240.1; -; mRNA.
DR CCDS; CCDS56961.1; -.
DR RefSeq; NP_065252.1; NM_020506.1.
DR PDB; 5DLQ; X-ray; 3.20 A; A/B=1-1151.
DR PDBsum; 5DLQ; -.
DR AlphaFoldDB; Q9ESJ0; -.
DR SMR; Q9ESJ0; -.
DR BioGRID; 208228; 4.
DR IntAct; Q9ESJ0; 2.
DR STRING; 10090.ENSMUSP00000133280; -.
DR iPTMnet; Q9ESJ0; -.
DR PhosphoSitePlus; Q9ESJ0; -.
DR EPD; Q9ESJ0; -.
DR jPOST; Q9ESJ0; -.
DR MaxQB; Q9ESJ0; -.
DR PaxDb; Q9ESJ0; -.
DR PeptideAtlas; Q9ESJ0; -.
DR PRIDE; Q9ESJ0; -.
DR ProteomicsDB; 299716; -.
DR Antibodypedia; 41969; 50 antibodies from 20 providers.
DR DNASU; 57258; -.
DR Ensembl; ENSMUST00000089482; ENSMUSP00000086909; ENSMUSG00000021952.
DR GeneID; 57258; -.
DR KEGG; mmu:57258; -.
DR UCSC; uc007udf.1; mouse.
DR CTD; 64328; -.
DR MGI; MGI:1888526; Xpo4.
DR VEuPathDB; HostDB:ENSMUSG00000021952; -.
DR eggNOG; KOG4541; Eukaryota.
DR GeneTree; ENSGT00940000153139; -.
DR InParanoid; Q9ESJ0; -.
DR OrthoDB; 106880at2759; -.
DR TreeFam; TF312991; -.
DR BioGRID-ORCS; 57258; 10 hits in 73 CRISPR screens.
DR ChiTaRS; Xpo4; mouse.
DR PRO; PR:Q9ESJ0; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q9ESJ0; protein.
DR Bgee; ENSMUSG00000021952; Expressed in primitive streak and 231 other tissues.
DR ExpressionAtlas; Q9ESJ0; baseline and differential.
DR Genevisible; Q9ESJ0; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005643; C:nuclear pore; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005049; F:nuclear export signal receptor activity; ISS:UniProtKB.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; ISO:MGI.
DR GO; GO:0006611; P:protein export from nucleus; IBA:GO_Central.
DR DisProt; DP02593; -.
DR Gene3D; 1.25.10.10; -; 2.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR044189; XPO4/7-like.
DR PANTHER; PTHR12596; PTHR12596; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Nucleus; Phosphoprotein; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..1151
FT /note="Exportin-4"
FT /id="PRO_0000204712"
FT MOD_RES 464
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 521
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 462
FT /note="E->R: Abolished binding to hypusinated EIF5A."
FT /evidence="ECO:0000269|PubMed:27306458"
FT MUTAGEN 465
FT /note="E->R: Abolished binding to hypusinated EIF5A."
FT /evidence="ECO:0000269|PubMed:27306458"
FT MUTAGEN 470
FT /note="D->N,R: Abolished binding to and nuclear export of
FT hypusinated EIF5A."
FT /evidence="ECO:0000269|PubMed:27306458"
FT MUTAGEN 537
FT /note="E->Q,R: Abolished binding to and nuclear export of
FT hypusinated EIF5A."
FT /evidence="ECO:0000269|PubMed:27306458"
FT MUTAGEN 631
FT /note="S->A,R: Abolished binding to and nuclear export of
FT hypusinated EIF5A."
FT /evidence="ECO:0000269|PubMed:27306458"
FT MUTAGEN 695
FT /note="S->R: Abolished binding to hypusinated EIF5A."
FT /evidence="ECO:0000269|PubMed:27306458"
FT CONFLICT 242
FT /note="K -> N (in Ref. 1; AAG09133 and 3; BAC98240)"
FT /evidence="ECO:0000305"
FT HELIX 9..22
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 26..28
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 31..45
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 51..60
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 64..80
FT /evidence="ECO:0007829|PDB:5DLQ"
FT TURN 81..84
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 87..103
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 109..128
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 134..146
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 150..166
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 186..192
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 194..211
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 217..234
FT /evidence="ECO:0007829|PDB:5DLQ"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 263..269
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 272..284
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 286..288
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 291..303
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 314..332
FT /evidence="ECO:0007829|PDB:5DLQ"
FT TURN 337..340
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 341..354
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 357..360
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 365..392
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 399..414
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 426..439
FT /evidence="ECO:0007829|PDB:5DLQ"
FT TURN 443..445
FT /evidence="ECO:0007829|PDB:5DLQ"
FT STRAND 451..453
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 470..473
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 475..487
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 489..513
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 529..550
FT /evidence="ECO:0007829|PDB:5DLQ"
FT STRAND 555..557
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 563..571
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 573..575
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 578..586
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 598..600
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 603..623
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 626..629
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 632..646
FT /evidence="ECO:0007829|PDB:5DLQ"
FT STRAND 649..651
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 654..656
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 662..668
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 673..692
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 697..711
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 714..720
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 724..734
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 738..741
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 745..758
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 765..775
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 777..786
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 794..797
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 799..817
FT /evidence="ECO:0007829|PDB:5DLQ"
FT TURN 821..826
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 827..844
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 849..866
FT /evidence="ECO:0007829|PDB:5DLQ"
FT TURN 867..869
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 872..893
FT /evidence="ECO:0007829|PDB:5DLQ"
FT STRAND 894..898
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 903..923
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 953..962
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 963..965
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 970..972
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 974..989
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 1000..1015
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 1019..1029
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 1030..1032
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 1047..1061
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 1072..1084
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 1086..1098
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 1103..1120
FT /evidence="ECO:0007829|PDB:5DLQ"
FT HELIX 1128..1144
FT /evidence="ECO:0007829|PDB:5DLQ"
SQ SEQUENCE 1151 AA; 129979 MW; 91428FC24FB54628 CRC64;
MMAAALGPPE VIAQLENAAK VLMAPPSMVS NEQRQHAEHI FLSFRKSKSP FAVCRHILET
SKVDYVLFQA ATAIMEAVVR EWVLLEKGSI ESLRTFLLTY VLQRPNLQKY VREQILLAVA
VIVKRGSLDK SIDCKSIFHE VSQLISSGNP TVQTLACSIL TALLSEFSSS SKTSNIGLSM
EFHGNCKRVF QEEDLRQIFM LTVGVLQEFS RRENLSAQMS SVFQRYLALA NQVLSWNFLP
PKLGRHYIAM FESSQNVLLK PTESWREALL DSRVMELFFT VHRKIREDSD MAQDSLQCLA
QLASLHGPIF PDEGSQVDYL AHFIEGLLNT INGIEIEDSE AVGISSIISN LITVFPRNVL
TAIPSELFSS FVNCLTHLTC SFGRSAALEE VLDKDDMVYM EAYDKLLESW LTLVRDDKHF
HKGFFTQHAV QVFNSYIQCH LAAPDGTRNL TANGVASREE EEISELQEDD RDQFSDQLAS
VGMLGRIAAE HCMPLLTSLL EERVTRLHGQ LQRHQQQFLA SPGSSTIDNK MLDDLYEDIH
WLILVTGYLL ADDTQGETPL IPPEIMEYSI KHSSEVDINT TLQILGSPGE KASSIPGYSR
TDSVIRLLSA VLRVSEVESR AIRADLTHLL SPQMGKDIVW FLKRWAKTYL LVDEKLYDQI
SLPLSTAFGA DTEGSQWIIG YLLQKVISNL SVWSSEQDLA NDTVQLLVTL VERRERANLV
IQCENWWNLA KQFASRSPPL NFLSSPVQRT LMKALVLGGF AHMDTETKQQ YWTEVLQPLQ
QRFLRVINQE NFQQMCQQEE VKQEITATLE ALCGIAEATQ IDNVAILFNF LMDFLNNCIG
LMEVYKNTPE TVNLIIEVFV EVAHKQICYL GESKAMHLYE ACLTLLQVYS KNNLGRQRID
VTAEEEQYQD LLLIMELLTN LLSKEFIDFS DTDEVFRGHE PGQAAGRSVS AADVVLYGVN
LILPLMSQDL LKFPTLCNQY YKLITFICEI FPEKIPQLPE DLFKSLMYSL ELGMTSMSSE
VCQLCLEALT PLAEQCAKAQ ETDSPLFLAT RHFLKLVFDM LVLQKHNTEM TTAAGEAFYT
LVCLHQAEYS ELVETLLSSQ QDPVIYQRLA DAFNKLTASS TPPALDRKQK MAFLKSLEEF
MANVGGLLCV K
