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 27-MAR-2024, entry version 189. 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 INTERACTION WITH LRPPRC. RX PubMed=28325843; DOI=10.1261/rna.060137.116; RA Volpon L., Culjkovic-Kraljacic B., Sohn H.S., Blanchet-Cohen A., RA Osborne M.J., Borden K.L.B.; RT "A biochemical framework for eIF4E-dependent mRNA export and nuclear RT recycling of the export machinery."; RL RNA 23:927-937(2017). RN [11] 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 [12] 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 [13] 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. Interacts with LRPPRC; the CC interaction occurs when LRPPRC is in its RNA-free form and promotes CC import of LRPPRC to the nucleus to allow for EIF4E-mediated export of CC mRNAS from the nucleus to the cytoplasm (PubMed:28325843). CC {ECO:0000269|PubMed:11682607, ECO:0000269|PubMed:28325843, 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 214. DR DIP; DIP-44186N; -. DR IntAct; O15397; 68. DR MINT; O15397; -. DR STRING; 9606.ENSP00000256079; -. DR TCDB; 1.I.1.1.3; the nuclear pore complex (npc) family. DR GlyGen; O15397; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O15397; -. DR PhosphoSitePlus; O15397; -. DR BioMuta; IPO8; -. DR EPD; O15397; -. DR jPOST; O15397; -. DR MassIVE; O15397; -. DR MaxQB; O15397; -. DR PaxDb; 9606-ENSP00000256079; -. DR PeptideAtlas; O15397; -. DR ProteomicsDB; 48636; -. [O15397-1] DR ProteomicsDB; 48637; -. [O15397-2] DR Pumba; O15397; -. DR Antibodypedia; 12794; 168 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 AGR; HGNC:9853; -. DR CTD; 10526; -. DR DisGeNET; 10526; -. DR GeneCards; IPO8; -. DR HGNC; HGNC:9853; IPO8. DR HPA; ENSG00000133704; Low tissue specificity. DR MalaCards; IPO8; -. DR MIM; 605600; gene. DR MIM; 619472; phenotype. DR neXtProt; NX_O15397; -. DR OpenTargets; ENSG00000133704; -. DR Orphanet; 60030; Loeys-Dietz syndrome. 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; KNFEYRS; -. DR OrthoDB; 168511at2759; -. 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; 17 hits in 1160 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 188 other cell types or tissues. DR ExpressionAtlas; O15397; baseline and differential. 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; Leucine-rich Repeat Variant; 1. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR001494; Importin-beta_N. DR InterPro; IPR013713; XPO2_central. DR PANTHER; PTHR10997; IMPORTIN-7, 8, 11; 1. DR PANTHER; PTHR10997:SF26; IMPORTIN-8; 1. DR Pfam; PF08506; Cse1; 1. DR Pfam; PF03810; IBN_N; 1. DR SMART; SM00913; IBN_N; 1. DR SUPFAM; SSF48371; ARM repeat; 1. DR PROSITE; PS50166; IMPORTIN_B_NT; 1. DR Genevisible; O15397; HS. 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 dbSNP:rs1234764565)" 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; uncertain 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 dbSNP:rs1425433912)" 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 //