IMA4_HUMAN
ID IMA4_HUMAN Reviewed; 521 AA.
AC O00505; O00191; O43195; Q5JVM9; Q8IYQ9; Q96AA7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Importin subunit alpha-4;
DE AltName: Full=Importin alpha Q2;
DE Short=Qip2;
DE AltName: Full=Karyopherin subunit alpha-3;
DE AltName: Full=SRP1-gamma;
GN Name=KPNA3; Synonyms=QIP2;
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].
RC TISSUE=Fetal brain;
RX PubMed=9154134; DOI=10.1159/000134521;
RA Takeda S., Fujiwara T., Shimizu F., Kawai A., Shinomiya K., Okuno S.,
RA Ozaki K., Katagiri T., Shimada Y., Nagata M., Watanabe T., Takaichi A.,
RA Kuga Y., Suzuki M., Hishigaki H., Takahashi E., Shin S., Nakamura Y.,
RA Hirai Y.;
RT "Isolation and mapping of karyopherin alpha 3 (KPNA3), a human gene that is
RT highly homologous to genes encoding Xenopus importin, yeast SRP1 and human
RT RCH1.";
RL Cytogenet. Cell Genet. 76:87-93(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=9395085; DOI=10.1016/s0014-5793(97)01265-9;
RA Koehler M., Ansieau S., Prehn S., Leutz A., Haller H., Hartmann E.;
RT "Cloning of two novel human importin-alpha subunits and analysis of the
RT expression pattern of the importin-alpha protein family.";
RL FEBS Lett. 417:104-108(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9435235; DOI=10.1073/pnas.95.2.582;
RA Nachury M.V., Ryder U.W., Lamond A.I., Weis K.;
RT "Cloning and characterization of hSRP1 gamma, a tissue-specific nuclear
RT transport factor.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:582-587(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Fischer R.;
RT "Importin alpha-3, a novel variant of the small importin subunit
RT evolutionarily conserved from hydrozoa to man.";
RL Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Muscle;
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 [9]
RP INTERACTION WITH INFLUENZA VIRUS NP (MICROBIAL INFECTION).
RX PubMed=12740372; DOI=10.1074/jbc.m303571200;
RA Melen K., Fagerlund R., Franke J., Koehler M., Kinnunen L., Julkunen I.;
RT "Importin alpha nuclear localization signal binding sites for STAT1, STAT2,
RT and influenza A virus nucleoprotein.";
RL J. Biol. Chem. 278:28193-28200(2003).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56 AND SER-60, 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 [15]
RP INTERACTION WITH HIV-1 INTEGRASE (MICROBIAL INFECTION).
RX PubMed=20554775; DOI=10.1128/jvi.00508-10;
RA Ao Z., Danappa Jayappa K., Wang B., Zheng Y., Kung S., Rassart E.,
RA Depping R., Kohler M., Cohen E.A., Yao X.;
RT "Importin alpha3 interacts with HIV-1 integrase and contributes to HIV-1
RT nuclear import and replication.";
RL J. Virol. 84:8650-8663(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56 AND SER-60, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND IDENTIFICATION BY
RP 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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56 AND SER-60, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56; SER-60 AND TYR-484, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP INTERACTION WITH NCBP2 AND NCBP3.
RX PubMed=26382858; DOI=10.1038/ncomms9192;
RA Gebhardt A., Habjan M., Benda C., Meiler A., Haas D.A., Hein M.Y., Mann A.,
RA Mann M., Habermann B., Pichlmair A.;
RT "mRNA export through an additional cap-binding complex consisting of NCBP1
RT and NCBP3.";
RL Nat. Commun. 6:8192-8192(2015).
CC -!- FUNCTION: Functions in nuclear protein import as an adapter protein for
CC nuclear receptor KPNB1. Binds specifically and directly to substrates
CC containing either a simple or bipartite NLS motif. Docking of the
CC importin/substrate complex to the nuclear pore complex (NPC) is
CC mediated by KPNB1 through binding to nucleoporin FxFG repeats and the
CC complex is subsequently translocated through the pore by an energy
CC requiring, Ran-dependent mechanism. At the nucleoplasmic side of the
CC NPC, Ran binds to importin-beta and the three components separate and
CC importin-alpha and -beta are re-exported from the nucleus to the
CC cytoplasm where GTP hydrolysis releases Ran from importin. 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
CC human cytomegalovirus UL84 by recognizing a non-classical NLS.
CC Recognizes NLSs of influenza A virus nucleoprotein probably through ARM
CC repeats 7-9.
CC -!- SUBUNIT: Forms a complex with importin subunit beta-1. Interacts with
CC NCBP2/CBP20 and NCBP3 (PubMed:26382858). {ECO:0000269|PubMed:26382858}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 integrase; this
CC interaction might play a role in nuclear import of HIV pre-integration
CC complex. {ECO:0000269|PubMed:20554775}.
CC -!- SUBUNIT: (Microbial infection) Interacts with influenza virus
CC nucleoprotein; this interaction might play a role in nuclear import of
CC viral genome. {ECO:0000269|PubMed:12740372}.
CC -!- INTERACTION:
CC O00505; Q9GZX7: AICDA; NbExp=2; IntAct=EBI-358297, EBI-3834328;
CC O00505; X5D778: ANKRD11; NbExp=3; IntAct=EBI-358297, EBI-17183751;
CC O00505; B3KTP4: ApoL6; NbExp=3; IntAct=EBI-358297, EBI-10175904;
CC O00505; Q8TBE0: BAHD1; NbExp=3; IntAct=EBI-358297, EBI-742750;
CC O00505; Q15059-2: BRD3; NbExp=3; IntAct=EBI-358297, EBI-13468085;
CC O00505; Q68D86: CCDC102B; NbExp=3; IntAct=EBI-358297, EBI-10171570;
CC O00505; P46527: CDKN1B; NbExp=4; IntAct=EBI-358297, EBI-519280;
CC O00505; Q6ZMK1-3: CYHR1; NbExp=3; IntAct=EBI-358297, EBI-11997340;
CC O00505; Q9NR30: DDX21; NbExp=3; IntAct=EBI-358297, EBI-357942;
CC O00505; P19447: ERCC3; NbExp=4; IntAct=EBI-358297, EBI-1183307;
CC O00505; Q92731-3: ESR2; NbExp=3; IntAct=EBI-358297, EBI-12259414;
CC O00505; Q7L5A3: FAM214B; NbExp=3; IntAct=EBI-358297, EBI-745689;
CC O00505; Q86YD7: FAM90A1; NbExp=4; IntAct=EBI-358297, EBI-6658203;
CC O00505; P02792: FTL; NbExp=3; IntAct=EBI-358297, EBI-713279;
CC O00505; Q13322-4: GRB10; NbExp=3; IntAct=EBI-358297, EBI-12353035;
CC O00505; Q96MH2: HEXIM2; NbExp=3; IntAct=EBI-358297, EBI-5460660;
CC O00505; P07910: HNRNPC; NbExp=5; IntAct=EBI-358297, EBI-357966;
CC O00505; P42858: HTT; NbExp=11; IntAct=EBI-358297, EBI-466029;
CC O00505; Q92993: KAT5; NbExp=3; IntAct=EBI-358297, EBI-399080;
CC O00505; Q14974: KPNB1; NbExp=3; IntAct=EBI-358297, EBI-286758;
CC O00505; Q8NA19-2: L3MBTL4; NbExp=3; IntAct=EBI-358297, EBI-12778187;
CC O00505; P45984: MAPK9; NbExp=3; IntAct=EBI-358297, EBI-713568;
CC O00505; Q9NZL9: MAT2B; NbExp=6; IntAct=EBI-358297, EBI-10317491;
CC O00505; Q13330: MTA1; NbExp=3; IntAct=EBI-358297, EBI-714236;
CC O00505; Q9HAN9: NMNAT1; NbExp=3; IntAct=EBI-358297, EBI-3917542;
CC O00505; Q9UKX7: NUP50; NbExp=6; IntAct=EBI-358297, EBI-2371082;
CC O00505; Q9BUI4: POLR3C; NbExp=3; IntAct=EBI-358297, EBI-5452779;
CC O00505; P43351: RAD52; NbExp=3; IntAct=EBI-358297, EBI-706448;
CC O00505; Q96P16: RPRD1A; NbExp=3; IntAct=EBI-358297, EBI-1053506;
CC O00505; Q8WWX8: SLC5A11; NbExp=3; IntAct=EBI-358297, EBI-10277669;
CC O00505; Q8WWX8-3: SLC5A11; NbExp=3; IntAct=EBI-358297, EBI-12697471;
CC O00505; Q96LM6: TEX37; NbExp=3; IntAct=EBI-358297, EBI-743976;
CC O00505; Q96KP6: TNIP3; NbExp=3; IntAct=EBI-358297, EBI-2509913;
CC O00505; Q9Y5U2: TSSC4; NbExp=4; IntAct=EBI-358297, EBI-717229;
CC O00505; Q2YD98: UVSSA; NbExp=3; IntAct=EBI-358297, EBI-11153331;
CC O00505; O43167: ZBTB24; NbExp=3; IntAct=EBI-358297, EBI-744471;
CC O00505; Q8TBK6: ZCCHC10; NbExp=3; IntAct=EBI-358297, EBI-597063;
CC O00505; Q6PEW1: ZCCHC12; NbExp=3; IntAct=EBI-358297, EBI-748373;
CC O00505; P36508: ZNF76; NbExp=3; IntAct=EBI-358297, EBI-7254550;
CC O00505; Q96H86: ZNF764; NbExp=3; IntAct=EBI-358297, EBI-745775;
CC O00505; Q9BRL8; NbExp=3; IntAct=EBI-358297, EBI-10297046;
CC O00505; K9N643: ORF4b; Xeno; NbExp=4; IntAct=EBI-358297, EBI-25641007;
CC O00505; P03427: PB2; Xeno; NbExp=3; IntAct=EBI-358297, EBI-8430745;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest levels in heart and skeletal
CC muscle.
CC -!- DOMAIN: Consists of an N-terminal hydrophilic region, a hydrophobic
CC central region composed of 10 repeats, and a short hydrophilic C-
CC terminus. The N-terminal hydrophilic region contains the importin beta
CC binding domain (IBB domain), which is sufficient for binding importin
CC beta and essential for nuclear protein import.
CC -!- DOMAIN: The IBB domain is thought to act as an intrasteric
CC autoregulatory sequence by interacting with the internal autoinhibitory
CC NLS. Binding of KPNB1 probably overlaps the internal NLS and
CC contributes to a high affinity for cytoplasmic NLS-containing cargo
CC substrates. After dissociation of the importin/substrate complex in the
CC nucleus the internal autohibitory NLS contributes to a low affinity for
CC nuclear NLS-containing proteins (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The major and minor NLS binding sites are mainly involved in
CC recognition of simple or bipartite NLS motifs. Structurally located
CC within in a helical surface groove they contain several conserved Trp
CC and Asn residues of the corresponding third helices (H3) of ARM repeats
CC which mainly contribute to binding (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the importin alpha family. {ECO:0000305}.
CC -!- CAUTION: Was termed importin alpha-4. {ECO:0000305|PubMed:9395085}.
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DR EMBL; D89618; BAA20378.1; -; mRNA.
DR EMBL; Y12394; CAA73026.1; -; mRNA.
DR EMBL; AF034756; AAB87693.1; -; mRNA.
DR EMBL; AF005263; AAQ13404.1; -; mRNA.
DR EMBL; AK290528; BAF83217.1; -; mRNA.
DR EMBL; AK291000; BAF83689.1; -; mRNA.
DR EMBL; AL136301; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL135901; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471075; EAX08837.1; -; Genomic_DNA.
DR EMBL; BC017355; AAH17355.1; -; mRNA.
DR EMBL; BC024202; AAH24202.1; -; mRNA.
DR EMBL; BC035090; AAH35090.1; -; mRNA.
DR CCDS; CCDS9421.1; -.
DR RefSeq; NP_002258.2; NM_002267.3.
DR AlphaFoldDB; O00505; -.
DR SMR; O00505; -.
DR BioGRID; 110037; 162.
DR ComplexPortal; CPX-1057; Importin complex, KPNA3 variant.
DR CORUM; O00505; -.
DR DIP; DIP-27586N; -.
DR IntAct; O00505; 108.
DR MINT; O00505; -.
DR STRING; 9606.ENSP00000261667; -.
DR ChEMBL; CHEMBL4523119; -.
DR TCDB; 1.I.1.1.3; the nuclear pore complex (npc) family.
DR GlyGen; O00505; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O00505; -.
DR PhosphoSitePlus; O00505; -.
DR SwissPalm; O00505; -.
DR BioMuta; KPNA3; -.
DR EPD; O00505; -.
DR jPOST; O00505; -.
DR MassIVE; O00505; -.
DR MaxQB; O00505; -.
DR PaxDb; O00505; -.
DR PeptideAtlas; O00505; -.
DR PRIDE; O00505; -.
DR ProteomicsDB; 47946; -.
DR Antibodypedia; 23966; 203 antibodies from 33 providers.
DR DNASU; 3839; -.
DR Ensembl; ENST00000261667.8; ENSP00000261667.3; ENSG00000102753.10.
DR GeneID; 3839; -.
DR KEGG; hsa:3839; -.
DR MANE-Select; ENST00000261667.8; ENSP00000261667.3; NM_002267.4; NP_002258.2.
DR UCSC; uc001vdj.2; human.
DR CTD; 3839; -.
DR DisGeNET; 3839; -.
DR GeneCards; KPNA3; -.
DR HGNC; HGNC:6396; KPNA3.
DR HPA; ENSG00000102753; Tissue enhanced (skeletal muscle, tongue).
DR MIM; 601892; gene.
DR neXtProt; NX_O00505; -.
DR OpenTargets; ENSG00000102753; -.
DR Orphanet; 171612; Autosomal dominant spastic paraplegia type 37.
DR PharmGKB; PA30187; -.
DR VEuPathDB; HostDB:ENSG00000102753; -.
DR eggNOG; KOG0166; Eukaryota.
DR GeneTree; ENSGT01050000244891; -.
DR HOGENOM; CLU_018084_6_1_1; -.
DR InParanoid; O00505; -.
DR OMA; XEAVWFL; -.
DR OrthoDB; 1111872at2759; -.
DR PhylomeDB; O00505; -.
DR TreeFam; TF101178; -.
DR PathwayCommons; O00505; -.
DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism.
DR Reactome; R-HSA-168276; NS1 Mediated Effects on Host Pathways.
DR SignaLink; O00505; -.
DR SIGNOR; O00505; -.
DR BioGRID-ORCS; 3839; 11 hits in 1082 CRISPR screens.
DR ChiTaRS; KPNA3; human.
DR GeneWiki; KPNA3; -.
DR GenomeRNAi; 3839; -.
DR Pharos; O00505; Tbio.
DR PRO; PR:O00505; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; O00505; protein.
DR Bgee; ENSG00000102753; Expressed in biceps brachii and 210 other tissues.
DR ExpressionAtlas; O00505; baseline and differential.
DR Genevisible; O00505; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043657; C:host cell; IEA:GOC.
DR GO; GO:0042564; C:NLS-dependent protein nuclear import complex; IPI:ComplexPortal.
DR GO; GO:0005643; C:nuclear pore; TAS:ProtInc.
DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0061608; F:nuclear import signal receptor activity; IBA:GO_Central.
DR GO; GO:0008139; F:nuclear localization sequence binding; IBA:GO_Central.
DR GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl.
DR GO; GO:0006607; P:NLS-bearing protein import into nucleus; IBA:GO_Central.
DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0075732; P:viral penetration into host nucleus; IEA:UniProtKB-KW.
DR Gene3D; 1.20.5.690; -; 1.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR032413; Arm_3.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR002652; Importin-a_IBB.
DR InterPro; IPR036975; Importin-a_IBB_sf.
DR InterPro; IPR024931; Importin_alpha.
DR Pfam; PF00514; Arm; 8.
DR Pfam; PF16186; Arm_3; 1.
DR Pfam; PF01749; IBB; 1.
DR PIRSF; PIRSF005673; Importin_alpha; 1.
DR SMART; SM00185; ARM; 8.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50176; ARM_REPEAT; 3.
DR PROSITE; PS51214; IBB; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Host-virus interaction; Nucleus; Phosphoprotein;
KW Protein transport; Reference proteome; Repeat; Transport;
KW Viral penetration into host nucleus; Virus entry into host cell.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..521
FT /note="Importin subunit alpha-4"
FT /id="PRO_0000120724"
FT DOMAIN 2..58
FT /note="IBB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00561"
FT REPEAT 66..106
FT /note="ARM 1; truncated"
FT REPEAT 107..149
FT /note="ARM 2"
FT REPEAT 150..194
FT /note="ARM 3"
FT REPEAT 195..233
FT /note="ARM 4"
FT REPEAT 234..278
FT /note="ARM 5"
FT REPEAT 279..318
FT /note="ARM 6"
FT REPEAT 319..360
FT /note="ARM 7"
FT REPEAT 361..400
FT /note="ARM 8"
FT REPEAT 401..443
FT /note="ARM 9"
FT REPEAT 447..485
FT /note="ARM 10; atypical"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 137..229
FT /note="NLS binding site (major)"
FT /evidence="ECO:0000250"
FT REGION 306..394
FT /note="NLS binding site (minor)"
FT /evidence="ECO:0000250"
FT MOTIF 43..52
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 9..29
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 56
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 484
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 291
FT /note="P -> S (in dbSNP:rs1043015)"
FT /id="VAR_014454"
FT CONFLICT 34
FT /note="V -> M (in Ref. 2; CAA73026)"
FT /evidence="ECO:0000305"
FT CONFLICT 103
FT /note="R -> Q (in Ref. 1; BAA20378)"
FT /evidence="ECO:0000305"
FT CONFLICT 152..153
FT /note="AV -> DI (in Ref. 8; AAH35090)"
FT /evidence="ECO:0000305"
FT CONFLICT 154
FT /note="V -> G (in Ref. 3; AAB87693)"
FT /evidence="ECO:0000305"
FT CONFLICT 236
FT /note="P -> T (in Ref. 3; AAB87693)"
FT /evidence="ECO:0000305"
FT CONFLICT 237
FT /note="M -> L (in Ref. 2; CAA73026)"
FT /evidence="ECO:0000305"
FT CONFLICT 256
FT /note="I -> V (in Ref. 2; CAA73026)"
FT /evidence="ECO:0000305"
FT CONFLICT 259
FT /note="L -> V (in Ref. 2; CAA73026)"
FT /evidence="ECO:0000305"
FT CONFLICT 332
FT /note="P -> Q (in Ref. 8; AAH35090)"
FT /evidence="ECO:0000305"
FT CONFLICT 411
FT /note="N -> D (in Ref. 8; AAH35090)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 521 AA; 57811 MW; C4FF132C3F346B7F CRC64;
MAENPSLENH RIKSFKNKGR DVETMRRHRN EVTVELRKNK RDEHLLKKRN VPQEESLEDS
DVDADFKAQN VTLEAILQNA TSDNPVVQLS AVQAARKLLS SDRNPPIDDL IKSGILPILV
KCLERDDNPS LQFEAAWALT NIASGTSAQT QAVVQSNAVP LFLRLLRSPH QNVCEQAVWA
LGNIIGDGPQ CRDYVISLGV VKPLLSFISP SIPITFLRNV TWVIVNLCRN KDPPPPMETV
QEILPALCVL IYHTDINILV DTVWALSYLT DGGNEQIQMV IDSGVVPFLV PLLSHQEVKV
QTAALRAVGN IVTGTDEQTQ VVLNCDVLSH FPNLLSHPKE KINKEAVWFL SNITAGNQQQ
VQAVIDAGLI PMIIHQLAKG DFGTQKEAAW AISNLTISGR KDQVEYLVQQ NVIPPFCNLL
SVKDSQVVQV VLDGLKNILI MAGDEASTIA EIIEECGGLE KIEVLQQHEN EDIYKLAFEI
IDQYFSGDDI DEDPCLIPEA TQGGTYNFDP TANLQTKEFN F
