ID   IPO8_DANRE              Reviewed;        1024 AA.
AC   A5WW24;
DT   03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT   10-JUL-2007, sequence version 1.
DT   03-AUG-2022, entry version 91.
DE   RecName: Full=Importin-8;
DE            Short=Imp8;
GN   Name=ipo8;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen;
RX   PubMed=23594743; DOI=10.1038/nature12111;
RA   Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA   Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA   Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA   White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA   Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA   Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA   Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA   Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA   Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA   Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA   Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA   Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA   Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA   Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA   Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA   McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA   Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA   Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA   Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA   Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA   Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA   Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA   Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA   Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA   Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA   Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA   Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA   Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA   de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA   Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT   "The zebrafish reference genome sequence and its relationship to the human
RT   genome.";
RL   Nature 496:498-503(2013).
RN   [2]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=34010604; DOI=10.1016/j.ajhg.2021.04.020;
RA   Ziegler A., Duclaux-Loras R., Revenu C., Charbit-Henrion F., Begue B.,
RA   Duroure K., Grimaud L., Guihot A.L., Desquiret-Dumas V., Zarhrate M.,
RA   Cagnard N., Mas E., Breton A., Edouard T., Billon C., Frank M., Colin E.,
RA   Lenaers G., Henrion D., Lyonnet S., Faivre L., Alembik Y., Philippe A.,
RA   Moulin B., Reinstein E., Tzur S., Attali R., McGillivray G., White S.M.,
RA   Gallacher L., Kutsche K., Schneeberger P., Girisha K.M., Nayak S.S.,
RA   Pais L., Maroofian R., Rad A., Vona B., Karimiani E.G., Lekszas C.,
RA   Haaf T., Martin L., Ruemmele F., Bonneau D., Cerf-Bensussan N.,
RA   Del Bene F., Parlato M.;
RT   "Bi-allelic variants in IPO8 cause a connective tissue disorder associated
RT   with cardiovascular defects, skeletal abnormalities, and immune
RT   dysregulation.";
RL   Am. J. Hum. Genet. 108:1126-1137(2021).
CC   -!- FUNCTION: Involved in nuclear protein import, either by acting as
CC       autonomous nuclear transport receptor or as an adapter-like protein in
CC       association with the importin-beta subunit KPNB1. Acting autonomously,
CC       may serve as receptor for nuclear localization signals (NLS) and
CC       promote translocation of import substrates through the nuclear pore
CC       complex (NPC) by an energy requiring, Ran-dependent mechanism. At the
CC       nucleoplasmic side of the NPC, Ran binds to importin, the
CC       importin/substrate complex dissociates and importin is re-exported from
CC       the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The
CC       directionality of nuclear import is thought to be conferred by an
CC       asymmetric distribution of the GTP- and GDP-bound forms of Ran between
CC       the cytoplasm and nucleus. In vitro mediates the nuclear import of the
CC       signal recognition particle protein SRP19 (By similarity). May also be
CC       involved in cytoplasm-to-nucleus shuttling of a broad spectrum of other
CC       cargos, including Argonaute-microRNAs complexes, the JUN protein,
CC       RELA/NF-kappa-B p65 subunit, the translation initiation factor EIF4E
CC       and a set of receptor-activated mothers against decapentaplegic homolog
CC       (SMAD) transcription factors that play a critical role downstream of
CC       the large family of transforming growth factor beta and bone
CC       morphogenetic protein (BMP) cytokines (Probable).
CC       {ECO:0000250|UniProtKB:O15397, ECO:0000305|PubMed:34010604}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Knockout animals present mild to severe dorso-
CC       ventral patterning defects during early embryonic development and
CC       display severe cardiovascular and skeletal defects.
CC       {ECO:0000269|PubMed:34010604}.
CC   -!- SIMILARITY: Belongs to the importin beta family. {ECO:0000305}.
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DR   EMBL; CT573126; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   SMR; A5WW24; -.
DR   STRING; 7955.ENSDARP00000110587; -.
DR   PaxDb; A5WW24; -.
DR   PeptideAtlas; A5WW24; -.
DR   Ensembl; ENSDART00000128937.4; ENSDARP00000110587.2; ENSDARG00000058159.8.
DR   ZFIN; ZDB-GENE-060503-3; ipo8.
DR   eggNOG; KOG1991; Eukaryota.
DR   GeneTree; ENSGT00940000158848; -.
DR   HOGENOM; CLU_004196_1_1_1; -.
DR   InParanoid; A5WW24; -.
DR   PhylomeDB; A5WW24; -.
DR   TreeFam; TF300634; -.
DR   Reactome; R-DRE-5578749; Transcriptional regulation by small RNAs.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 4.
DR   Bgee; ENSDARG00000058159; Expressed in zone of skin and 27 other tissues.
DR   ExpressionAtlas; A5WW24; baseline.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005635; C:nuclear envelope; IBA:GO_Central.
DR   GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR   GO; GO:0006606; P:protein import into nucleus; IBA:GO_Central.
DR   Gene3D; 1.25.10.10; -; 1.
DR   InterPro; IPR011989; ARM-like.
DR   InterPro; IPR016024; ARM-type_fold.
DR   InterPro; IPR001494; Importin-beta_N.
DR   Pfam; PF03810; IBN_N; 1.
DR   SMART; SM00913; IBN_N; 1.
DR   SUPFAM; SSF48371; SSF48371; 1.
DR   PROSITE; PS50166; IMPORTIN_B_NT; 1.
PE   3: Inferred from homology;
KW   Cytoplasm; Nucleus; Protein transport; Reference proteome; Transport.
FT   CHAIN           1..1024
FT                   /note="Importin-8"
FT                   /id="PRO_0000455801"
FT   DOMAIN          22..102
FT                   /note="Importin N-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00115"
SQ   SEQUENCE   1024 AA;  118053 MW;  28D2C0E16C8E43BE CRC64;
     MDPNRIIQAL KGTIDPNLRL AAENELNQSY KIINFAPTLL QIIVSEQVEF PVRQAAAIYL
     KNMVSQYWQD REPTLGEVVF PFNIHENDRG QIRENMVEAI IRCPESIRAQ LTVCLRAIIK
     HDFPGRWTGV VDKINLYLQS QNSGSWYGSL LALYQLVKNY EFKKAEERDP LLAAMQIFLP
     RLQQLITQLL SDATFISVLI QKQILKIFHA LVQLINNTVM THWMEILRTV VDRDVPAIWF
     SECLRGGFQE TLEADEDDRP ELIWWKCKKW ALHILTRIFE RYGSPGNVTK EYVEFADFFL
     KTYALGIQQV LLKVMEQHRQ RQYVSPRVLQ QTLSFMTQGV SHSLTWRQMK PHMQTITHEL
     VFPLMCYKDE DERLWQEDPY EYIRMKFNVY DDHVSPATAA QTLLCTAARK RKEVLPQMME
     FCHQILVDPS ADPRRTDGAL HVIGTLAQPL LKKRVYRDQM ELMLQNYVFP LLNSNLAYLR
     ARSCWVLHSF SPLKFHNELV LRNAVELVKH NLVEDKEMPV KVEAAIALQT LVRNQEQAKV
     YIRPFIRPVM QELLHIIKET ENDDLTGVIQ KMICEYSEEV TVIAVDMTQN LAEIFSKILQ
     SEEYEESEDK TVMALGILST IDTILTVMGD RKEISQQLEG ICLQVIGLVL QKPIIGMAEF
     YEEILSLAFG LTCYCISPQM WQLLGVLYDV FQHDCFDYFT DMMPLLHNYV TVDTNMLLSD
     PKYLEVIYTM CKKVLTSDAG EDPECHAAKL LEVIILQCRG RGIDQCIPLF VEAVLERLTR
     GVKSSELRTM CLQVVIAALY YNPTLLIHTL ENIRFPHSPE PITAQFINQW MNDTEFFLGL
     HDRKMCVIGL SILMELPSRP AVLEEVVGQI VPSVLLLFLG LKHIYASRVL NKPEQFGRAQ
     GSEEEENEEI PSDEDEVGEK GVALQPSVAP TGNDNEDDDD EDDDEYWDDE GLEGTPLEEY
     STPLDCDNGE DEYQFFTASL LRVQSSDAGW YQSLTSPLNE DQRKQLQEIY NLAQQRRSTG
     VKGL