IPO8_HUMAN
ID IPO8_HUMAN Reviewed; 1037 AA.
AC O15397; B7Z7M3;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Importin-8;
DE Short=Imp8;
DE AltName: Full=Ran-binding protein 8;
DE Short=RanBP8;
GN Name=IPO8; Synonyms=RANBP8;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH KPNB1,
RP AND VARIANT PHE-6.
RX PubMed=9214382; DOI=10.1083/jcb.138.1.65;
RA Goerlich D., Dabrowski M., Bischoff F.R., Kutay U., Bork P., Hartmann E.,
RA Prehn S., Izaurralde E.;
RT "A novel class of RanGTP binding proteins.";
RL J. Cell Biol. 138:65-80(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP FUNCTION, AND INTERACTION WITH RPL23A AND SRP19.
RX PubMed=11682607; DOI=10.1242/jcs.114.19.3479;
RA Dean K.A., von Ahsen O., Goerlich D., Fried H.M.;
RT "Signal recognition particle protein 19 is imported into the nucleus by
RT importin 8 (RanBP8) and transportin.";
RL J. Cell Sci. 114:3479-3485(2001).
RN [5]
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 the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-902 AND SER-903, AND
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-902 AND SER-903, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [8]
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., Buerckstuemmer T.,
RA 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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-902 AND SER-903, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP INVOLVEMENT IN VISS, VARIANTS VISS 259-TRP--ASN-1037 DEL AND
RP 474-ARG--ASN-1037 DEL, AND CHARACTERIZATION OF VARIANT VISS
RP 474-ARG--ASN-1037 DEL.
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).
RN [11]
RP INVOLVEMENT IN VISS, VARIANTS VISS 28-GLN--ASN-1037 DEL; ASN-88;
RP 710-SER--ASN-1037 DEL; ARG-749; 803-ARG--ASN-1037 DEL AND TRP-834, AND
RP CHARACTERIZATION OF VARIANTS VISS 28-GLN--ASN-1037 DEL; ASN-88; ARG-749 AND
RP TRP-834.
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).
RN [12]
RP INVOLVEMENT IN VISS, AND VARIANTS VISS 234-ARG--ASN-1037 DEL;
RP 259-TRP--ASN-1037 DEL; CYS-317 AND 645-GLN--ASN-1037 DEL.
RX PubMed=33875846; DOI=10.1038/s41436-021-01159-0;
RA Bertoli-Avella A.M., Kandaswamy K.K., Khan S., Ordonez-Herrera N.,
RA Tripolszki K., Beetz C., Rocha M.E., Urzi A., Hotakainen R., Leubauer A.,
RA Al-Ali R., Karageorgou V., Moldovan O., Dias P., Alhashem A., Tabarki B.,
RA Albalwi M.A., Alswaid A.F., Al-Hassnan Z.N., Alghamdi M.A., Hadipour Z.,
RA Hadipour F., Al Hashmi N., Al-Gazali L., Cheema H., Zaki M.S., Huening I.,
RA Alfares A., Eyaid W., Al Mutairi F., Alfadhel M., Alkuraya F.S.,
RA Al-Sannaa N.A., AlShamsi A.M., Ameziane N., Rolfs A., Bauer P.;
RT "Combining exome/genome sequencing with data repository analysis reveals
RT novel gene-disease associations for a wide range of genetic disorders.";
RL Genet. Med. 23:1551-1568(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 (PubMed:9214382). In vitro mediates the
CC nuclear import of the signal recognition particle protein SRP19
CC (PubMed:11682607). May also be involved in cytoplasm-to-nucleus
CC shuttling of a broad spectrum of other cargos, including Argonaute-
CC microRNAs complexes, the JUN protein, RELA/NF-kappa-B p65 subunit, the
CC translation initiation factor EIF4E and a set of receptor-activated
CC mothers against decapentaplegic homolog (SMAD) transcription factors
CC that play a critical role downstream of the large family of
CC transforming growth factor beta and bone morphogenetic protein (BMP)
CC cytokines (Probable). {ECO:0000269|PubMed:11682607,
CC ECO:0000269|PubMed:9214382, ECO:0000305|PubMed:34010604}.
CC -!- SUBUNIT: Forms a heterodimer with KPNB1 (PubMed:9214382). Interacts
CC with SRP19 (PubMed:11682607). Interacts with RPL23A (PubMed:11682607).
CC Binds directly to nuclear pore complexes. {ECO:0000269|PubMed:11682607,
CC ECO:0000269|PubMed:9214382}.
CC -!- INTERACTION:
CC O15397; Q9UL18: AGO1; NbExp=2; IntAct=EBI-358808, EBI-527363;
CC O15397; Q9UKV8: AGO2; NbExp=4; IntAct=EBI-358808, EBI-528269;
CC O15397; Q9H9G7: AGO3; NbExp=5; IntAct=EBI-358808, EBI-2267883;
CC O15397; Q9HCK5: AGO4; NbExp=3; IntAct=EBI-358808, EBI-2269696;
CC O15397; Q15797: SMAD1; NbExp=2; IntAct=EBI-358808, EBI-1567153;
CC O15397; P84022: SMAD3; NbExp=2; IntAct=EBI-358808, EBI-347161;
CC O15397; P19532: TFE3; NbExp=2; IntAct=EBI-358808, EBI-1048957;
CC O15397; P19544-6: WT1; NbExp=3; IntAct=EBI-358808, EBI-11745701;
CC O15397; Q6ZN57: ZFP2; NbExp=3; IntAct=EBI-358808, EBI-7236323;
CC O15397; O43296: ZNF264; NbExp=3; IntAct=EBI-358808, EBI-4395808;
CC O15397; Q6NX45: ZNF774; NbExp=3; IntAct=EBI-358808, EBI-10251462;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O15397-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O15397-2; Sequence=VSP_042574;
CC -!- DISEASE: VISS syndrome (VISS) [MIM:619472]: An autosomal recessive
CC disease characterized by early-onset thoracic aortic aneurysm, aneurysm
CC and tortuosity of other arteries, motor developmental delay, connective
CC tissue findings such as joint hypermobility, skin laxity and hernias,
CC and craniofacial dysmorphic features. Immune dysregulation has been
CC reported in some patients. {ECO:0000269|PubMed:33875846,
CC ECO:0000269|PubMed:34010604, ECO:0000269|PubMed:34010605}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the importin beta family. {ECO:0000305}.
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DR EMBL; U77494; AAB67052.1; -; mRNA.
DR EMBL; AK302260; BAH13659.1; -; mRNA.
DR EMBL; AC012673; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC023426; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS53773.1; -. [O15397-2]
DR CCDS; CCDS8719.1; -. [O15397-1]
DR RefSeq; NP_001177924.1; NM_001190995.1. [O15397-2]
DR RefSeq; NP_006381.2; NM_006390.3. [O15397-1]
DR AlphaFoldDB; O15397; -.
DR SMR; O15397; -.
DR BioGRID; 115781; 191.
DR DIP; DIP-44186N; -.
DR IntAct; O15397; 67.
DR MINT; O15397; -.
DR STRING; 9606.ENSP00000256079; -.
DR TCDB; 1.I.1.1.3; the nuclear pore complex (npc) family.
DR iPTMnet; O15397; -.
DR PhosphoSitePlus; O15397; -.
DR BioMuta; IPO8; -.
DR EPD; O15397; -.
DR jPOST; O15397; -.
DR MassIVE; O15397; -.
DR MaxQB; O15397; -.
DR PaxDb; O15397; -.
DR PeptideAtlas; O15397; -.
DR PRIDE; O15397; -.
DR ProteomicsDB; 48636; -. [O15397-1]
DR ProteomicsDB; 48637; -. [O15397-2]
DR Antibodypedia; 12794; 145 antibodies from 30 providers.
DR DNASU; 10526; -.
DR Ensembl; ENST00000256079.9; ENSP00000256079.4; ENSG00000133704.10. [O15397-1]
DR Ensembl; ENST00000544829.5; ENSP00000444520.1; ENSG00000133704.10. [O15397-2]
DR GeneID; 10526; -.
DR KEGG; hsa:10526; -.
DR MANE-Select; ENST00000256079.9; ENSP00000256079.4; NM_006390.4; NP_006381.2.
DR UCSC; uc001rjd.4; human. [O15397-1]
DR CTD; 10526; -.
DR DisGeNET; 10526; -.
DR GeneCards; IPO8; -.
DR HGNC; HGNC:9853; IPO8.
DR HPA; ENSG00000133704; Low tissue specificity.
DR MIM; 605600; gene.
DR MIM; 619472; phenotype.
DR neXtProt; NX_O15397; -.
DR OpenTargets; ENSG00000133704; -.
DR PharmGKB; PA34214; -.
DR VEuPathDB; HostDB:ENSG00000133704; -.
DR eggNOG; KOG1991; Eukaryota.
DR GeneTree; ENSGT00940000158848; -.
DR HOGENOM; CLU_004196_1_1_1; -.
DR InParanoid; O15397; -.
DR OMA; VVAWMNI; -.
DR OrthoDB; 159062at2759; -.
DR PhylomeDB; O15397; -.
DR TreeFam; TF300634; -.
DR PathwayCommons; O15397; -.
DR Reactome; R-HSA-5578749; Transcriptional regulation by small RNAs.
DR SignaLink; O15397; -.
DR BioGRID-ORCS; 10526; 16 hits in 1082 CRISPR screens.
DR ChiTaRS; IPO8; human.
DR GenomeRNAi; 10526; -.
DR Pharos; O15397; Tbio.
DR PRO; PR:O15397; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; O15397; protein.
DR Bgee; ENSG00000133704; Expressed in secondary oocyte and 186 other tissues.
DR ExpressionAtlas; O15397; baseline and differential.
DR Genevisible; O15397; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005635; C:nuclear envelope; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0031267; F:small GTPase binding; TAS:ProtInc.
DR GO; GO:0006606; P:protein import into nucleus; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
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; Aortic aneurysm; Cytoplasm; Disease variant; Nucleus;
KW Phosphoprotein; Protein transport; Reference proteome; Transport.
FT CHAIN 1..1037
FT /note="Importin-8"
FT /id="PRO_0000120752"
FT DOMAIN 22..102
FT /note="Importin N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00115"
FT REGION 886..934
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 902
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692"
FT MOD_RES 903
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692"
FT VAR_SEQ 1..213
FT /note="MDLNRIIQALKGTIDPKLRIAAENELNQSYKIINFAPSLLRIIVSDHVEFPV
FT RQAAAIYLKNMVTQYWPDREPPPGEAIFPFNIHENDRQQIRDNIVEGIIRSPDLVRVQL
FT TMCLRAIIKHDFPGHWPGVVDKIDYYLQSQSSASWLGSLLCLYQLVKTYEYKKAEEREP
FT LIIAMQIFLPRIQQQIVQLLPDSSYYSVLLQKQILKIFYALVQ -> MESLTLKG (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042574"
FT VARIANT 6
FT /note="I -> F (in dbSNP:rs1054423)"
FT /evidence="ECO:0000269|PubMed:9214382"
FT /id="VAR_055118"
FT VARIANT 28..1037
FT /note="Missing (in VISS; undetectable protein levels in
FT either patient's fibroblasts or patient's Epstein-Barr
FT virus-immortalized B cell lines)"
FT /evidence="ECO:0000269|PubMed:34010604"
FT /id="VAR_086233"
FT VARIANT 88
FT /note="D -> N (in VISS; very low protein expression levels,
FT if any, in either patient's fibroblasts or patient's
FT Epstein-Barr virus-immortalized B cell lines)"
FT /evidence="ECO:0000269|PubMed:34010604"
FT /id="VAR_086234"
FT VARIANT 234..1037
FT /note="Missing (in VISS)"
FT /evidence="ECO:0000269|PubMed:33875846"
FT /id="VAR_086235"
FT VARIANT 259..1037
FT /note="Missing (in VISS)"
FT /evidence="ECO:0000269|PubMed:33875846,
FT ECO:0000269|PubMed:34010605"
FT /id="VAR_086236"
FT VARIANT 317
FT /note="Y -> C (in VISS; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:33875846"
FT /id="VAR_086237"
FT VARIANT 474..1037
FT /note="Missing (in VISS; undetectable protein levels in
FT patient's fibroblasts, although mRNA levels seem
FT unaffected)"
FT /evidence="ECO:0000269|PubMed:34010605"
FT /id="VAR_086238"
FT VARIANT 640
FT /note="I -> V (in dbSNP:rs34119940)"
FT /id="VAR_055119"
FT VARIANT 645..1037
FT /note="Missing (in VISS)"
FT /evidence="ECO:0000269|PubMed:33875846"
FT /id="VAR_086239"
FT VARIANT 710..1037
FT /note="Missing (in VISS)"
FT /evidence="ECO:0000269|PubMed:34010604"
FT /id="VAR_086240"
FT VARIANT 749
FT /note="C -> R (in VISS; undetectable protein expression
FT levels in either patient's fibroblasts or patient's
FT Epstein-Barr virus-immortalized B cell lines)"
FT /evidence="ECO:0000269|PubMed:34010604"
FT /id="VAR_086241"
FT VARIANT 803..1037
FT /note="Missing (in VISS)"
FT /evidence="ECO:0000269|PubMed:34010604"
FT /id="VAR_086242"
FT VARIANT 834
FT /note="R -> W (in VISS; very low protein expression levels,
FT if any, in either patient's fibroblasts or patient's
FT Epstein-Barr virus-immortalized B cell lines)"
FT /evidence="ECO:0000269|PubMed:34010604"
FT /id="VAR_086243"
FT CONFLICT 91
FT /note="Q -> R (in Ref. 1; AAB67052)"
FT /evidence="ECO:0000305"
FT CONFLICT 279
FT /note="P -> A (in Ref. 1; AAB67052)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1037 AA; 119938 MW; 3D7195FD57D7D9AF CRC64;
MDLNRIIQAL KGTIDPKLRI AAENELNQSY KIINFAPSLL RIIVSDHVEF PVRQAAAIYL
KNMVTQYWPD REPPPGEAIF PFNIHENDRQ QIRDNIVEGI IRSPDLVRVQ LTMCLRAIIK
HDFPGHWPGV VDKIDYYLQS QSSASWLGSL LCLYQLVKTY EYKKAEEREP LIIAMQIFLP
RIQQQIVQLL PDSSYYSVLL QKQILKIFYA LVQYALPLQL VNNQTMTTWM EIFRTIIDRT
VPPETLHIDE DDRPELVWWK CKKWALHIVA RLFERYGSPG NVTKEYFEFS EFFLKTYAVG
IQQVLLKILD QYRQKEYVAP RVLQQAFNYL NQGVVHSITW KQMKPHIQNI SEDVIFSVMC
YKDEDEELWQ EDPYEYIRMK FDIFEDYASP TTAAQTLLYT AAKKRKEVLP KMMAFCYQIL
TDPNFDPRKK DGALHVIGSL AEILLKKSLF KDQMELFLQN HVFPLLLSNL GYLRARSCWV
LHAFSSLKFH NELNLRNAVE LAKKSLIEDK EMPVKVEAAL ALQSLISNQI QAKEYMKPHV
RPIMQELLHI VRETENDDVT NVIQKMICEY SQEVASIAVD MTQHLAEIFG KVLQSDEYEE
VEDKTVMAMG ILHTIDTILT VVEDHKEITQ QLENICLRII DLVLQKHVIE FYEEILSLAY
SLTCHSISPQ MWQLLGILYE VFQQDCFEYF TDMMPLLHNY VTIDTDTLLS NAKHLEILFT
MCRKVLCGDA GEDAECHAAK LLEVIILQCK GRGIDQCIPL FVQLVLERLT RGVKTSELRT
MCLQVAIAAL YYNPDLLLHT LERIQLPHNP GPITVQFINQ WMNDTDCFLG HHDRKMCIIG
LSILLELQNR PPAVDAVVGQ IVPSILFLFL GLKQVCATRQ LVNREDRSKA EKADMEENEE
ISSDEEETNV TAQAMQSNNG RGEDEEEEDD DWDEEVLEET ALEGFSTPLD LDNSVDEYQF
FTQALITVQS RDAAWYQLLM APLSEDQRTA LQEVYTLAEH RRTVAEAKKK IEQQGGFTFE
NKGVLSAFNF GTVPSNN
