IPO8_MOUSE
ID IPO8_MOUSE Reviewed; 1010 AA.
AC Q7TMY7; B2KGD8; Q811I3; Q8C8A9; Q8R2P6; Q8R3V7;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Importin-8;
DE Short=Imp8;
DE AltName: Full=Ran-binding protein 8;
DE Short=RanBP8;
GN Name=Ipo8;
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-406 AND 654-1010 (ISOFORMS 1 AND 2).
RC STRAIN=FVB/N, and FVB/N-3; TISSUE=Brain, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 71-401 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 407-653.
RG The MGC Project Team;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP RECONSTRUCTION FROM ESTS, AND CONCEPTUAL TRANSLATION OF 407-653.
RA Argoud-Puy G.;
RL Unpublished observations (JAN-2004).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, Lung, 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 [9]
RP DISRUPTION PHENOTYPE.
RX PubMed=34010605; DOI=10.1016/j.ajhg.2021.04.019;
RG Genomics England Research Consortium;
RA Van Gucht I., Meester J.A.N., Bento J.R., Bastiaansen M., Bastianen J.,
RA Luyckx I., Van Den Heuvel L., Neutel C.H.G., Guns P.J., Vermont M.,
RA Fransen E., Perik M.H.A.M., Velchev J.D., Alaerts M., Schepers D.,
RA Peeters S., Pintelon I., Almesned A., Ferla M.P., Taylor J.C.,
RA Dallosso A.R., Williams M., Evans J., Rosenfeld J.A., Sluysmans T.,
RA Rodrigues D., Chikermane A., Bharmappanavara G., Vijayakumar K.,
RA Mottaghi Moghaddam Shahri H., Hashemi N., Torbati P.N., Toosi M.B.,
RA Al-Hassnan Z.N., Vogt J., Revencu N., Maystadt I., Miller E.M.,
RA Weaver K.N., Begtrup A., Houlden H., Murphy D., Maroofian R.,
RA Pagnamenta A.T., Van Laer L., Loeys B.L., Verstraeten A.;
RT "A human importin-beta-related disorder: Syndromic thoracic aortic aneurysm
RT caused by bi-allelic loss-of-function variants in IPO8.";
RL Am. J. Hum. Genet. 108:1115-1125(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. May also be involved in
CC cytoplasm-to-nucleus shuttling of a broad spectrum of other cargos,
CC including Argonaute-microRNAs complexes, the JUN protein, RELA/NF-
CC kappa-B p65 subunit, the translation initiation factor EIF4E and a set
CC of receptor-activated mothers against decapentaplegic homolog (SMAD)
CC transcription factors that play a critical role downstream of the large
CC family of transforming growth factor beta and bone morphogenetic
CC protein (BMP) cytokines. {ECO:0000250|UniProtKB:O15397}.
CC -!- SUBUNIT: Forms a heterodimer with KPNB1. Interacts with SRP19.
CC Interacts with RPL23A. Binds directly to nuclear pore complexes.
CC {ECO:0000250|UniProtKB:O15397}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7TMY7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7TMY7-2; Sequence=VSP_009656;
CC -!- DISRUPTION PHENOTYPE: Knockout animals present with reduced grip
CC strength and diminished vertical activity. Progressive dilatation can
CC be observed in the aortic root at the level of the sinuses of Valsalva
CC and distal ascending aorta, and aneurysms of the distal ascending aorta
CC are becoming visible at the age of 8-12 weeks. Generally, males are
CC more severely affected, exhibiting larger aortas and experiencing
CC dissection and/or rupture more frequently than females.
CC {ECO:0000269|PubMed:34010605}.
CC -!- SIMILARITY: Belongs to the importin beta family. {ECO:0000305}.
CC -!- CAUTION: The regions from 407 to 653 were deduced from the genomic
CC sequence and ESTs by similarity to the human sequence. {ECO:0000305}.
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DR EMBL; CU302294; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466572; EDL10748.1; -; Genomic_DNA.
DR EMBL; BC024474; AAH24474.1; -; mRNA.
DR EMBL; BC027360; AAH27360.1; -; mRNA.
DR EMBL; BC044819; AAH44819.1; -; mRNA.
DR EMBL; BC054373; AAH54373.1; -; mRNA.
DR EMBL; BC151036; AAI51037.1; -; mRNA.
DR EMBL; BC151052; AAI51053.1; -; mRNA.
DR EMBL; AK047854; BAC33175.1; -; mRNA.
DR EMBL; CD350256; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BQ770006; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS39719.1; -. [Q7TMY7-1]
DR RefSeq; NP_001074582.1; NM_001081113.1. [Q7TMY7-1]
DR AlphaFoldDB; Q7TMY7; -.
DR SMR; Q7TMY7; -.
DR BioGRID; 236248; 3.
DR IntAct; Q7TMY7; 2.
DR STRING; 10090.ENSMUSP00000046759; -.
DR iPTMnet; Q7TMY7; -.
DR PhosphoSitePlus; Q7TMY7; -.
DR EPD; Q7TMY7; -.
DR jPOST; Q7TMY7; -.
DR MaxQB; Q7TMY7; -.
DR PaxDb; Q7TMY7; -.
DR PeptideAtlas; Q7TMY7; -.
DR PRIDE; Q7TMY7; -.
DR ProteomicsDB; 269084; -. [Q7TMY7-1]
DR ProteomicsDB; 269085; -. [Q7TMY7-2]
DR Antibodypedia; 12794; 145 antibodies from 30 providers.
DR Ensembl; ENSMUST00000048418; ENSMUSP00000046759; ENSMUSG00000040029. [Q7TMY7-1]
DR GeneID; 320727; -.
DR KEGG; mmu:320727; -.
DR UCSC; uc009etl.1; mouse. [Q7TMY7-1]
DR UCSC; uc009etn.2; mouse. [Q7TMY7-2]
DR CTD; 10526; -.
DR MGI; MGI:2444611; Ipo8.
DR VEuPathDB; HostDB:ENSMUSG00000040029; -.
DR eggNOG; KOG1991; Eukaryota.
DR GeneTree; ENSGT00940000158848; -.
DR HOGENOM; CLU_004196_1_1_1; -.
DR InParanoid; Q7TMY7; -.
DR OMA; VVAWMNI; -.
DR OrthoDB; 159062at2759; -.
DR PhylomeDB; Q7TMY7; -.
DR TreeFam; TF300634; -.
DR Reactome; R-MMU-5578749; Transcriptional regulation by small RNAs.
DR BioGRID-ORCS; 320727; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Ipo8; mouse.
DR PRO; PR:Q7TMY7; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q7TMY7; protein.
DR Bgee; ENSMUSG00000040029; Expressed in secondary oocyte and 252 other tissues.
DR ExpressionAtlas; Q7TMY7; baseline and differential.
DR Genevisible; Q7TMY7; MM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; ISA:MGI.
DR GO; GO:0005635; C:nuclear envelope; IBA:GO_Central.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; ISA:MGI.
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 InterPro; IPR013713; XPO2_central.
DR Pfam; PF08506; Cse1; 1.
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 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Nucleus; Phosphoprotein;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..1010
FT /note="Importin-8"
FT /id="PRO_0000120753"
FT DOMAIN 22..102
FT /note="Importin N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00115"
FT REGION 886..932
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 902
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15397"
FT MOD_RES 903
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15397"
FT VAR_SEQ 304..347
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009656"
FT CONFLICT 405
FT /note="R -> K (in Ref. 3; AAH44819/AAH54373)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1010 AA; 117078 MW; 56BFECF32695BD7A CRC64;
MDLNRIIQAL KGTIDPKLRI AAETELNQSY KIINFAPSLL RIIVSDHVEF PVRQAAAIYL
KNMVTQYWPD REPPPGEVIF PFNIHENDRQ QIRDNIVEGI IRSPDLVRVQ LTMCLRVIIR
HDFPGHWPAV VDKIDYYLQS PNSGSWLGSL LCLYQLVKTY EYKKAEEREP LLAAMQIFLP
RIQQQILQLL PDASHYSVLL QKQILKIFYA LVQYALPLQL VNHQTMTTWM EIFRTIIDRT
VPPETLQIDE DDRPELVWWK CKKWALHIVA RLFERYGSPG NVTKEYFEFS EFFLKTYAVG
IQQVLLKILD QYRQKEYIAP RVLQQAFNYL NQGVVHAVTW KQMKPHIQNI SEDVIFSVMC
YKDEDEELWQ EDPYEYIRMK FDIFEDYASP TTAAQTLLYT AAKKRKEVLP KMMAFCYQIL
TDPNFDPRKK DGALHVIGSL AEILLKKSLF KDQIELFLQN HVFPLLMSNL GYLRARSCWV
LHAFSSLKFH NELNLRNAVE LAKKSLIEDE EMPVKVEAAL ALQSLISNQA QAKEHMKPYV
RFIMQELLHI VRETENDDVT NVIQKLICEY SQDVASIAVD TTQHLAEIFG KVLQSDEYEE
IEDKTVMAMG ILHTIDTILT VVEDHPEIIQ QLENICLRII DLVLQKHVIE FYEEILSLAY
NLTCHTISPQ MWQLLGILYE VFQQDCFEYF TDMMPLLHNY VTVDTNALLS NPKHLEVLFT
MCRKVLCGEA GEDAECYAAK LLEVIILQCK GRGIDQCIPL FIQLVLERLT RGVKTSELRT
MCLQVAIAAL YYSPELLFHT LEQVQLPHNP GPVTSQFINQ WMNDTDYFLG HHDRKMCIIG
LSVLLELQNR PPAVDAVAAQ ILPSILFLFL GLKQVCATRQ TVNRENHSKA EKVDIEENEE
ISSEEEEETS VSAQAMQSQI GRSEEEDDDD WDEEVLEETA LEGFSTPLDL DNSVDEYQFF
TQALLTVQNR DAAWYQLLVA PLSEDQKRKL QEVYTLAEHR RTLAAGQFHI
