ID   IMA1_HUMAN              Reviewed;         529 AA.
AC   P52292; B9EJD6; Q53YE3; Q6NVW7; Q9BRU5;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   12-AUG-2020, entry version 233.
DE   RecName: Full=Importin subunit alpha-1 {ECO:0000305};
DE   AltName: Full=Karyopherin subunit alpha-2;
DE   AltName: Full=RAG cohort protein 1;
DE   AltName: Full=SRP1-alpha;
GN   Name=KPNA2 {ECO:0000312|HGNC:HGNC:6395}; Synonyms=RCH1, SRP1;
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].
RX   PubMed=7754385; DOI=10.1126/science.7754385;
RA   Weis K., Mattaj I.W., Lamond A.I.;
RT   "Identification of hSRP1 alpha as a functional receptor for nuclear
RT   localization sequences.";
RL   Science 268:1049-1053(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-165.
RX   PubMed=11735022; DOI=10.1007/s004390100605;
RA   Doerr S., Schlicker M., Hansmann I.;
RT   "Genomic structure of karyopherin alpha2 (KPNA2) within a low-copy repeat
RT   on chromosome 17q23-q24 and mutation analysis in patients with Russell-
RT   Silver syndrome.";
RL   Hum. Genet. 109:479-486(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-157 AND ASN-453.
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-157; ARG-165 AND
RP   ASN-453.
RC   TISSUE=Bone marrow, and Testis;
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   [6]
RP   PROTEIN SEQUENCE OF 2-13; 69-101; 107-117; 239-258; 292-315; 354-388 AND
RP   487-494, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Hepatoma;
RA   Bienvenut W.V., Boldt K., von Kriegsheim A.F., Kolch W.;
RL   Submitted (JUL-2007) to UniProtKB.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 33-529.
RC   TISSUE=Cervix carcinoma;
RX   PubMed=8016130; DOI=10.1073/pnas.91.13.6156;
RA   Cuomo C.A., Kirch S.A., Gyuris J., Brent R., Oettinger M.A.;
RT   "Rch1, a protein that specifically interacts with the RAG-1 recombination-
RT   activating protein.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:6156-6160(1994).
RN   [8]
RP   SUBUNIT, AND SUBCELLULAR LOCATION.
RX   PubMed=7604027; DOI=10.1073/pnas.92.14.6532;
RA   Moroianu J., Hijikata M., Blobel G., Radu A.;
RT   "Mammalian karyopherin alpha 1 beta and alpha 2 beta heterodimers: alpha 1
RT   or alpha 2 subunit binds nuclear localization signal and beta subunit
RT   interacts with peptide repeat-containing nucleoporins.";
RL   Proc. Natl. Acad. Sci. U.S.A. 92:6532-6536(1995).
RN   [9]
RP   DOMAIN IBB.
RX   PubMed=8617227; DOI=10.1002/j.1460-2075.1996.tb00531.x;
RA   Weis K., Ryder U., Lamond A.I.;
RT   "The conserved amino-terminal domain of hSRP1 alpha is essential for
RT   nuclear protein import.";
RL   EMBO J. 15:1818-1825(1996).
RN   [10]
RP   IDENTIFICATION IN A COMPLEX WITH RAN AND CSE1L.
RX   PubMed=9323134; DOI=10.1016/s0092-8674(00)80372-4;
RA   Kutay U., Bischoff F.R., Kostka S., Kraft R., Goerlich D.;
RT   "Export of importin-alpha from the nucleus is mediated by a specific
RT   nuclear transport factor.";
RL   Cell 90:1061-1071(1997).
RN   [11]
RP   INTERACTION WITH HIV-1 VPR (MICROBIAL INFECTION).
RX   PubMed=9463369; DOI=10.1093/emboj/17.4.909;
RA   Popov S., Rexach M., Zybarth G., Reiling N., Lee M.A., Ratner L.,
RA   Lane C.M., Moore M.S., Blobel G., Bukrinsky M.;
RT   "Viral protein R regulates nuclear import of the HIV-1 pre-integration
RT   complex.";
RL   EMBO J. 17:909-917(1998).
RN   [12]
RP   INTERACTION WITH XPO2/CSE1L.
RX   PubMed=9786944; DOI=10.1083/jcb.143.2.309;
RA   Herold A., Truant R., Wiegand H., Cullen B.R.;
RT   "Determination of the functional domain organization of the importin alpha
RT   nuclear import factor.";
RL   J. Cell Biol. 143:309-318(1998).
RN   [13]
RP   INTERACTION WITH ARL4A.
RX   PubMed=10980193; DOI=10.1074/jbc.m002470200;
RA   Lin C.Y., Huang P.H., Liao W.L., Cheng H.J., Huang C.F., Kuo J.C.,
RA   Patton W.A., Massenburg D., Moss J., Lee F.J.;
RT   "ARL4, an ARF-like protein that is developmentally regulated and localized
RT   to nuclei and nucleoli.";
RL   J. Biol. Chem. 275:37815-37823(2000).
RN   [14]
RP   INTERACTION WITH PLAG1.
RX   PubMed=11882654; DOI=10.1074/jbc.m112112200;
RA   Braem C.V., Kas K., Meyen E., Debiec-Rychter M., Van De Ven W.J.M.,
RA   Voz M.L.;
RT   "Identification of a karyopherin alpha 2 recognition site in PLAG1, which
RT   functions as a nuclear localization signal.";
RL   J. Biol. Chem. 277:19673-19678(2002).
RN   [15]
RP   MASS SPECTROMETRY.
RC   TISSUE=Mammary cancer;
RX   PubMed=11840567;
RX   DOI=10.1002/1615-9861(200202)2:2<212::aid-prot212>3.0.co;2-h;
RA   Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A.,
RA   Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J.,
RA   Zvelebil M.J.;
RT   "Cluster analysis of an extensive human breast cancer cell line protein
RT   expression map database.";
RL   Proteomics 2:212-223(2002).
RN   [16]
RP   INTERACTION WITH NBN.
RX   PubMed=16188882; DOI=10.1074/jbc.m508425200;
RA   Tseng S.-F., Chang C.-Y., Wu K.-J., Teng S.-C.;
RT   "Importin KPNA2 is required for proper nuclear localization and multiple
RT   functions of NBS1.";
RL   J. Biol. Chem. 280:39594-39600(2005).
RN   [17]
RP   INTERACTION WITH APEX1.
RX   PubMed=15942031; DOI=10.1093/nar/gki641;
RA   Jackson E.B., Theriot C.A., Chattopadhyay R., Mitra S., Izumi T.;
RT   "Analysis of nuclear transport signals in the human apurinic/apyrimidinic
RT   endonuclease (APE1/Ref1).";
RL   Nucleic Acids Res. 33:3303-3312(2005).
RN   [18]
RP   IDENTIFICATION BY 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   [19]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=16964243; DOI=10.1038/nbt1240;
RA   Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT   "A probability-based approach for high-throughput protein phosphorylation
RT   analysis and site localization.";
RL   Nat. Biotechnol. 24:1285-1292(2006).
RN   [20]
RP   INTERACTION WITH SARS VIRUS ORF6 PROTEIN (MICROBIAL INFECTION), SUBCELLULAR
RP   LOCATION (MICROBIAL INFECTION), MUTAGENESIS OF 2-SER--ASP-80, AND
RP   INTERACTION WITH KPNB1.
RX   PubMed=17596301; DOI=10.1128/jvi.01012-07;
RA   Frieman M., Yount B., Heise M., Kopecky-Bromberg S.A., Palese P.,
RA   Baric R.S.;
RT   "Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1
RT   function by sequestering nuclear import factors on the rough endoplasmic
RT   reticulum/Golgi membrane.";
RL   J. Virol. 81:9812-9824(2007).
RN   [21]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18220336; DOI=10.1021/pr0705441;
RA   Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT   "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT   phosphoproteomic analysis.";
RL   J. Proteome Res. 7:1346-1351(2008).
RN   [22]
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   [23]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-490, 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   [24]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT SER-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   [25]
RP   INTERACTION WITH SNAI1 AND SNAI2.
RX   PubMed=19386897; DOI=10.1242/jcs.041749;
RA   Mingot J.M., Vega S., Maestro B., Sanz J.M., Nieto M.A.;
RT   "Characterization of Snail nuclear import pathways as representatives of
RT   C2H2 zinc finger transcription factors.";
RL   J. Cell Sci. 122:1452-1460(2009).
RN   [26]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, AND IDENTIFICATION BY
RP   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   [27]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-490, 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   [28]
RP   IDENTIFICATION IN COMPLEX WITH CRM1 AND VENEZUELAN EQUINE ENCEPHALITIS
RP   VIRUS CAPSID PROTEIN (MICROBIAL INFECTION).
RX   PubMed=20147401; DOI=10.1128/jvi.02554-09;
RA   Atasheva S., Fish A., Fornerod M., Frolova E.I.;
RT   "Venezuelan equine encephalitis virus capsid protein forms a tetrameric
RT   complex with CRM1 and importin alpha/beta that obstructs nuclear pore
RT   complex function.";
RL   J. Virol. 84:4158-4171(2010).
RN   [29]
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   [30]
RP   INTERACTION WITH SNAI1.
RX   PubMed=21454664; DOI=10.1074/jbc.m110.213579;
RA   Sekimoto T., Miyamoto Y., Arai S., Yoneda Y.;
RT   "Importin alpha protein acts as a negative regulator for Snail protein
RT   nuclear import.";
RL   J. Biol. Chem. 286:15126-15131(2011).
RN   [31]
RP   INTERACTION WITH CTNNBL1.
RX   PubMed=21385873; DOI=10.1074/jbc.m110.208769;
RA   Ganesh K., Adam S., Taylor B., Simpson P., Rada C., Neuberger M.;
RT   "CTNNBL1 is a novel nuclear localization sequence-binding protein that
RT   recognizes RNA-splicing factors CDC5L and Prp31.";
RL   J. Biol. Chem. 286:17091-17102(2011).
RN   [32]
RP   INTERACTION WITH FRG1.
RX   PubMed=21699900; DOI=10.1016/j.jmb.2011.06.014;
RA   Sun C.Y., van Koningsbruggen S., Long S.W., Straasheijm K., Klooster R.,
RA   Jones T.I., Bellini M., Levesque L., Brieher W.M., van der Maarel S.M.,
RA   Jones P.L.;
RT   "Facioscapulohumeral muscular dystrophy region gene 1 is a dynamic RNA-
RT   associated and actin-bundling protein.";
RL   J. Mol. Biol. 411:397-416(2011).
RN   [33]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP   ANALYSIS] AT SER-62, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE
RP   ANALYSIS], AND 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   [34]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [35]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-490, 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   [36]
RP   INTERACTION WITH BAG6.
RX   PubMed=29042515; DOI=10.1073/pnas.1702940114;
RA   Mock J.Y., Xu Y., Ye Y., Clemons W.M. Jr.;
RT   "Structural basis for regulation of the nucleo-cytoplasmic distribution of
RT   Bag6 by TRC35.";
RL   Proc. Natl. Acad. Sci. U.S.A. 114:11679-11684(2017).
RN   [37]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 11-54.
RX   PubMed=10353244; DOI=10.1038/20367;
RA   Cingolani G., Petosa C., Weis K., Muller C.W.;
RT   "Structure of importin-beta bound to the IBB domain of importin-alpha.";
RL   Nature 399:221-229(1999).
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.
CC   -!- SUBUNIT: Heterodimer; with KPNB1 (PubMed:17596301). Interacts with
CC       ANP32E (By similarity). Component of a complex containing CSE1L, RAN
CC       and KPNA2. Interacts directly with CSE1L. Interacts with PLAG1.
CC       Interacts with APEX1 (via N-terminus). Interacts with FRG1 (via N-
CC       terminus). Interacts with ARL4A, CTNNBL1 and NBN. Interacts with SNAI1
CC       (via zinc fingers) and SNAI2 (via zinc fingers). Interacts with BAG6
CC       (PubMed:29042515). Interacts with AIFM2; this interaction likely
CC       mediates the translocation of AIFM2 into the nucleus upon oxidative
CC       stress. {ECO:0000250, ECO:0000250|UniProtKB:P52293,
CC       ECO:0000269|PubMed:10980193, ECO:0000269|PubMed:11882654,
CC       ECO:0000269|PubMed:15942031, ECO:0000269|PubMed:16188882,
CC       ECO:0000269|PubMed:17596301, ECO:0000269|PubMed:19386897,
CC       ECO:0000269|PubMed:21385873, ECO:0000269|PubMed:21454664,
CC       ECO:0000269|PubMed:21699900, ECO:0000269|PubMed:29042515,
CC       ECO:0000269|PubMed:7604027, ECO:0000269|PubMed:9323134,
CC       ECO:0000269|PubMed:9786944}.
CC   -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 Vpr.
CC       {ECO:0000269|PubMed:9463369}.
CC   -!- SUBUNIT: (Microbial infection) Part of a tetrameric complex composed of
CC       CRM1, importin alpha/beta dimer and the Venezuelan equine encephalitis
CC       virus (VEEV) capsid; this complex blocks the receptor-mediated
CC       transport through the nuclear pore. {ECO:0000269|PubMed:20147401}.
CC   -!- SUBUNIT: (Microbial infection) Interacts with SARS-COV virus ORF6
CC       protein; this interaction blocks the receptor-mediated transport
CC       through the nuclear pore. {ECO:0000269|PubMed:17596301}.
CC   -!- INTERACTION:
CC       P52292; P63010: AP2B1; NbExp=3; IntAct=EBI-349938, EBI-432924;
CC       P52292; P38398: BRCA1; NbExp=3; IntAct=EBI-349938, EBI-349905;
CC       P52292; Q96C86: DCPS; NbExp=3; IntAct=EBI-349938, EBI-3917181;
CC       P52292; Q53SE7: FLJ13057; NbExp=3; IntAct=EBI-349938, EBI-10172181;
CC       P52292; Q9NP66: HMG20A; NbExp=3; IntAct=EBI-349938, EBI-740641;
CC       P52292; P07910: HNRNPC; NbExp=4; IntAct=EBI-349938, EBI-357966;
CC       P52292; Q8IX15-3: HOMEZ; NbExp=3; IntAct=EBI-349938, EBI-10172004;
CC       P52292; Q8NBZ0: INO80E; NbExp=3; IntAct=EBI-349938, EBI-769401;
CC       P52292; P05412: JUN; NbExp=4; IntAct=EBI-349938, EBI-852823;
CC       P52292; Q14974: KPNB1; NbExp=10; IntAct=EBI-349938, EBI-286758;
CC       P52292; Q14974-1: KPNB1; NbExp=4; IntAct=EBI-349938, EBI-15488647;
CC       P52292; Q6A162: KRT40; NbExp=3; IntAct=EBI-349938, EBI-10171697;
CC       P52292; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-349938, EBI-741037;
CC       P52292; Q9Y5V3: MAGED1; NbExp=4; IntAct=EBI-349938, EBI-716006;
CC       P52292; Q99750: MDFI; NbExp=3; IntAct=EBI-349938, EBI-724076;
CC       P52292; P40692: MLH1; NbExp=9; IntAct=EBI-349938, EBI-744248;
CC       P52292; Q9UBU8-2: MORF4L1; NbExp=3; IntAct=EBI-349938, EBI-10288852;
CC       P52292; Q7Z6G3-2: NECAB2; NbExp=3; IntAct=EBI-349938, EBI-10172876;
CC       P52292; Q9HAN9: NMNAT1; NbExp=8; IntAct=EBI-349938, EBI-3917542;
CC       P52292; Q9UKX7: NUP50; NbExp=9; IntAct=EBI-349938, EBI-2371082;
CC       P52292; P37198: NUP62; NbExp=3; IntAct=EBI-349938, EBI-347978;
CC       P52292; Q86Y26: NUTM1; NbExp=3; IntAct=EBI-349938, EBI-10178410;
CC       P52292; Q96PV4: PNMA5; NbExp=3; IntAct=EBI-349938, EBI-10171633;
CC       P52292; Q93062: RBPMS; NbExp=3; IntAct=EBI-349938, EBI-740322;
CC       P52292; P46063: RECQL; NbExp=2; IntAct=EBI-349938, EBI-2823728;
CC       P52292; O43148: RNMT; NbExp=3; IntAct=EBI-349938, EBI-877832;
CC       P52292; P29034: S100A2; NbExp=5; IntAct=EBI-349938, EBI-752230;
CC       P52292; P06703: S100A6; NbExp=3; IntAct=EBI-349938, EBI-352877;
CC       P52292; Q9UJW9: SERTAD3; NbExp=4; IntAct=EBI-349938, EBI-748621;
CC       P52292; Q15637: SF1; NbExp=5; IntAct=EBI-349938, EBI-744603;
CC       P52292; Q9UH99: SUN2; NbExp=3; IntAct=EBI-349938, EBI-1044964;
CC       P52292; O75478: TADA2A; NbExp=3; IntAct=EBI-349938, EBI-742268;
CC       P52292; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-349938, EBI-2130429;
CC       P52292; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-349938, EBI-739895;
CC       P52292; P03101: L1; Xeno; NbExp=3; IntAct=EBI-349938, EBI-7362698;
CC       P52292; P03107: L2; Xeno; NbExp=3; IntAct=EBI-349938, EBI-7362531;
CC       P52292; Q6GQG6: npm2; Xeno; NbExp=2; IntAct=EBI-349938, EBI-8469111;
CC       P52292; P04620: rev; Xeno; NbExp=2; IntAct=EBI-349938, EBI-10687101;
CC       P52292; A0A3G5BIZ0; Xeno; NbExp=6; IntAct=EBI-349938, EBI-25564606;
CC       P52292; P03070; Xeno; NbExp=2; IntAct=EBI-349938, EBI-617698;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7604027}. Nucleus
CC       {ECO:0000269|PubMed:7604027}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane. Golgi apparatus
CC       membrane {ECO:0000269|PubMed:17596301}. Note=(Microbial infection)
CC       Retained in ER/Golgi membranes upon interaction with SARS-COV virus
CC       ORF6 protein. {ECO:0000269|PubMed:17596301}.
CC   -!- TISSUE SPECIFICITY: Expressed ubiquitously.
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       {ECO:0000269|PubMed:8617227}.
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   -!- MASS SPECTROMETRY: Mass=57861.92; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:11840567};
CC   -!- SIMILARITY: Belongs to the importin alpha family. {ECO:0000305}.
DR   EMBL; U28386; AAA69957.1; -; mRNA.
DR   EMBL; AJ303086; CAC83080.1; -; Genomic_DNA.
DR   EMBL; BT006665; AAP35311.1; -; mRNA.
DR   EMBL; CH471099; EAW89041.1; -; Genomic_DNA.
DR   EMBL; BC005978; AAH05978.1; -; mRNA.
DR   EMBL; BC067848; AAH67848.1; -; mRNA.
DR   EMBL; BC146905; AAI46906.1; -; mRNA.
DR   EMBL; U09559; AAA65700.1; -; mRNA.
DR   CCDS; CCDS32713.1; -.
DR   PIR; A56516; A56516.
DR   RefSeq; NP_001307540.1; NM_001320611.1.
DR   RefSeq; NP_002257.1; NM_002266.3.
DR   PDB; 1EFX; X-ray; 3.00 A; C=204-212.
DR   PDB; 1QGK; X-ray; 2.50 A; B=11-54.
DR   PDB; 1QGR; X-ray; 2.30 A; B=28-54.
DR   PDB; 3FEX; X-ray; 3.55 A; C=70-529.
DR   PDB; 3FEY; X-ray; 2.20 A; C=70-529.
DR   PDB; 3WPT; X-ray; 2.63 A; A/B=75-497.
DR   PDB; 4E4V; X-ray; 2.53 A; A/B=70-529.
DR   PDB; 4WV6; X-ray; 1.75 A; A=60-529.
DR   PDB; 5H43; X-ray; 2.30 A; A=70-497.
DR   PDBsum; 1EFX; -.
DR   PDBsum; 1QGK; -.
DR   PDBsum; 1QGR; -.
DR   PDBsum; 3FEX; -.
DR   PDBsum; 3FEY; -.
DR   PDBsum; 3WPT; -.
DR   PDBsum; 4E4V; -.
DR   PDBsum; 4WV6; -.
DR   PDBsum; 5H43; -.
DR   SMR; P52292; -.
DR   BioGRID; 110036; 252.
DR   ComplexPortal; CPX-1027; Importin complex, KPNA2 variant.
DR   CORUM; P52292; -.
DR   DIP; DIP-6205N; -.
DR   IntAct; P52292; 160.
DR   MINT; P52292; -.
DR   STRING; 9606.ENSP00000438483; -.
DR   BindingDB; P52292; -.
DR   ChEMBL; CHEMBL1741187; -.
DR   TCDB; 1.I.1.1.3; the nuclear pore complex (npc) family.
DR   iPTMnet; P52292; -.
DR   PhosphoSitePlus; P52292; -.
DR   SwissPalm; P52292; -.
DR   BioMuta; KPNA2; -.
DR   DMDM; 1708480; -.
DR   SWISS-2DPAGE; P52292; -.
DR   CPTAC; CPTAC-232; -.
DR   CPTAC; CPTAC-233; -.
DR   EPD; P52292; -.
DR   jPOST; P52292; -.
DR   MassIVE; P52292; -.
DR   MaxQB; P52292; -.
DR   PaxDb; P52292; -.
DR   PeptideAtlas; P52292; -.
DR   PRIDE; P52292; -.
DR   ProteomicsDB; 56475; -.
DR   Antibodypedia; 4226; 415 antibodies.
DR   DNASU; 3838; -.
DR   Ensembl; ENST00000330459; ENSP00000332455; ENSG00000182481.
DR   Ensembl; ENST00000537025; ENSP00000438483; ENSG00000182481.
DR   GeneID; 3838; -.
DR   KEGG; hsa:3838; -.
DR   UCSC; uc002jgk.4; human.
DR   CTD; 3838; -.
DR   DisGeNET; 3838; -.
DR   EuPathDB; HostDB:ENSG00000182481.8; -.
DR   GeneCards; KPNA2; -.
DR   HGNC; HGNC:6395; KPNA2.
DR   HPA; ENSG00000182481; Tissue enhanced (testis).
DR   MIM; 600685; gene.
DR   neXtProt; NX_P52292; -.
DR   OpenTargets; ENSG00000182481; -.
DR   PharmGKB; PA30186; -.
DR   eggNOG; KOG0166; Eukaryota.
DR   GeneTree; ENSGT01000000214531; -.
DR   HOGENOM; CLU_018084_6_1_1; -.
DR   InParanoid; P52292; -.
DR   KO; K15043; -.
DR   OMA; IVPICIR; -.
DR   OrthoDB; 1111872at2759; -.
DR   PhylomeDB; P52292; -.
DR   TreeFam; TF101178; -.
DR   PathwayCommons; P52292; -.
DR   Reactome; R-HSA-111932; CaMK IV-mediated phosphorylation of CREB.
DR   Reactome; R-HSA-1169408; ISG15 antiviral mechanism.
DR   Reactome; R-HSA-168276; NS1 Mediated Effects on Host Pathways.
DR   Reactome; R-HSA-442729; CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde.
DR   Reactome; R-HSA-5693548; Sensing of DNA Double Strand Breaks.
DR   Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR   SignaLink; P52292; -.
DR   SIGNOR; P52292; -.
DR   BioGRID-ORCS; 3838; 73 hits in 880 CRISPR screens.
DR   ChiTaRS; KPNA2; human.
DR   EvolutionaryTrace; P52292; -.
DR   GeneWiki; Karyopherin_alpha_2; -.
DR   GenomeRNAi; 3838; -.
DR   Pharos; P52292; Tbio.
DR   PRO; PR:P52292; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; P52292; protein.
DR   Bgee; ENSG00000182481; Expressed in testis and 114 other tissues.
DR   ExpressionAtlas; P52292; baseline and differential.
DR   Genevisible; P52292; HS.
DR   GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0098892; C:extrinsic component of postsynaptic specialization membrane; IDA:SynGO.
DR   GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:0042025; C:host cell nucleus; IEA:InterPro.
DR   GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0042826; F:histone deacetylase binding; IPI:BHF-UCL.
DR   GO; GO:0061608; F:nuclear import signal receptor activity; IBA:GO_Central.
DR   GO; GO:0008139; F:nuclear localization sequence binding; IDA:UniProtKB.
DR   GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR   GO; GO:0006259; P:DNA metabolic process; TAS:ProtInc.
DR   GO; GO:0075506; P:entry of viral genome into host nucleus through nuclear pore complex via importin; IMP:MGI.
DR   GO; GO:0019054; P:modulation by virus of host cellular process; TAS:Reactome.
DR   GO; GO:0006607; P:NLS-bearing protein import into nucleus; IDA:UniProtKB.
DR   GO; GO:1903902; P:positive regulation of viral life cycle; IMP:MGI.
DR   GO; GO:0099527; P:postsynapse to nucleus signaling pathway; IDA:SynGO.
DR   GO; GO:0000018; P:regulation of DNA recombination; TAS:ProtInc.
DR   Gene3D; 1.20.5.690; -; 1.
DR   Gene3D; 1.25.10.10; -; 1.
DR   IDEAL; IID00153; -.
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; Importing_su_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; 5.
DR   PROSITE; PS51214; IBB; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Cytoplasm; Direct protein sequencing;
KW   Endoplasmic reticulum; Golgi apparatus; Host-virus interaction; Membrane;
KW   Nucleus; Phosphoprotein; Polymorphism; Protein transport;
KW   Reference proteome; Repeat; Transport.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000244|PubMed:19413330,
FT                   ECO:0000244|PubMed:21406692, ECO:0000244|PubMed:22814378,
FT                   ECO:0000269|Ref.6"
FT   CHAIN           2..529
FT                   /note="Importin subunit alpha-1"
FT                   /id="PRO_0000120722"
FT   DOMAIN          2..60
FT                   /note="IBB"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00561"
FT   REPEAT          71..111
FT                   /note="ARM 1; truncated"
FT   REPEAT          112..151
FT                   /note="ARM 2"
FT   REPEAT          152..193
FT                   /note="ARM 3"
FT   REPEAT          200..244
FT                   /note="ARM 4"
FT   REPEAT          246..282
FT                   /note="ARM 5"
FT   REPEAT          283..322
FT                   /note="ARM 6"
FT   REPEAT          325..364
FT                   /note="ARM 7"
FT   REPEAT          367..409
FT                   /note="ARM 8"
FT   REPEAT          410..456
FT                   /note="ARM 9"
FT   REPEAT          457..496
FT                   /note="ARM 10; atypical"
FT   REGION          142..238
FT                   /note="NLS binding site (major)"
FT                   /evidence="ECO:0000250"
FT   REGION          315..403
FT                   /note="NLS binding site (minor)"
FT                   /evidence="ECO:0000250"
FT   MOTIF           45..54
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        28..31
FT                   /note="Poly-Arg"
FT   COMPBIAS        499..502
FT                   /note="Poly-Glu"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000244|PubMed:19413330,
FT                   ECO:0000244|PubMed:21406692, ECO:0000244|PubMed:22814378,
FT                   ECO:0000269|Ref.6"
FT   MOD_RES         62
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:16964243,
FT                   ECO:0000244|PubMed:18669648, ECO:0000244|PubMed:19690332,
FT                   ECO:0000244|PubMed:20068231, ECO:0000244|PubMed:21406692,
FT                   ECO:0000244|PubMed:23186163"
FT   MOD_RES         490
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:18669648,
FT                   ECO:0000244|PubMed:20068231, ECO:0000244|PubMed:23186163"
FT   VARIANT         157
FT                   /note="A -> V (in dbSNP:rs17850032)"
FT                   /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3"
FT                   /id="VAR_067625"
FT   VARIANT         165
FT                   /note="P -> R (in dbSNP:rs11545989)"
FT                   /evidence="ECO:0000269|PubMed:11735022,
FT                   ECO:0000269|PubMed:15489334"
FT                   /id="VAR_013137"
FT   VARIANT         365
FT                   /note="G -> S (in dbSNP:rs1059558)"
FT                   /id="VAR_067626"
FT   VARIANT         453
FT                   /note="K -> N (in dbSNP:rs17850031)"
FT                   /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3"
FT                   /id="VAR_067627"
FT   MUTAGEN         2..80
FT                   /note="Missing: Complete loss of binding to KPNB1."
FT                   /evidence="ECO:0000269|PubMed:17596301"
FT   CONFLICT        182
FT                   /note="A -> D (in Ref. 5; AAH67848)"
FT                   /evidence="ECO:0000305"
FT   HELIX           14..16
FT                   /evidence="ECO:0000244|PDB:1QGK"
FT   TURN            18..21
FT                   /evidence="ECO:0000244|PDB:1QGK"
FT   HELIX           30..48
FT                   /evidence="ECO:0000244|PDB:1QGR"
FT   HELIX           74..85
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           90..104
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   STRAND          106..108
FT                   /evidence="ECO:0000244|PDB:3FEY"
FT   HELIX           112..117
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           121..128
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           134..148
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           152..160
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           163..170
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           176..190
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           194..202
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           206..213
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   STRAND          214..216
FT                   /evidence="ECO:0000244|PDB:5H43"
FT   HELIX           218..220
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           223..236
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           246..259
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           265..278
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           283..290
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   TURN            291..293
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           295..302
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           307..320
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           325..333
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           336..339
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           340..344
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           349..362
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           367..375
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           379..388
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           391..407
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           410..418
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           422..427
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           428..430
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           434..454
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           457..466
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           469..475
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           476..478
FT                   /evidence="ECO:0000244|PDB:4WV6"
FT   HELIX           479..481
FT                   /evidence="ECO:0000244|PDB:3WPT"
FT   HELIX           482..495
FT                   /evidence="ECO:0000244|PDB:4WV6"
SQ   SEQUENCE   529 AA;  57862 MW;  B0F94A0475B80EED CRC64;
     MSTNENANTP AARLHRFKNK GKDSTEMRRR RIEVNVELRK AKKDDQMLKR RNVSSFPDDA
     TSPLQENRNN QGTVNWSVDD IVKGINSSNV ENQLQATQAA RKLLSREKQP PIDNIIRAGL
     IPKFVSFLGR TDCSPIQFES AWALTNIASG TSEQTKAVVD GGAIPAFISL LASPHAHISE
     QAVWALGNIA GDGSVFRDLV IKYGAVDPLL ALLAVPDMSS LACGYLRNLT WTLSNLCRNK
     NPAPPIDAVE QILPTLVRLL HHDDPEVLAD TCWAISYLTD GPNERIGMVV KTGVVPQLVK
     LLGASELPIV TPALRAIGNI VTGTDEQTQV VIDAGALAVF PSLLTNPKTN IQKEATWTMS
     NITAGRQDQI QQVVNHGLVP FLVSVLSKAD FKTQKEAVWA VTNYTSGGTV EQIVYLVHCG
     IIEPLMNLLT AKDTKIILVI LDAISNIFQA AEKLGETEKL SIMIEECGGL DKIEALQNHE
     NESVYKASLS LIEKYFSVEE EEDQNVVPET TSEGYTFQVQ DGAPGTFNF
//