IMA1_HUMAN
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 03-AUG-2022, entry version 242.
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 INTERACTION WITH ZIKA VIRUS RNA-DIRECTED RNA POLYMERASE NS5 (MICROBIAL
RP INFECTION).
RX PubMed=30848123; DOI=10.1021/acsinfecdis.8b00373;
RA Ng I.H.W., Chan K.W., Tan M.J.A., Gwee C.P., Smith K.M., Jeffress S.J.,
RA Saw W.G., Swarbrick C.M.D., Watanabe S., Jans D.A., Grueber G.,
RA Forwood J.K., Vasudevan S.G.;
RT "Zika Virus NS5 Forms Supramolecular Nuclear Bodies That Sequester
RT Importin-alpha and Modulate the Host Immune and Pro-Inflammatory Response
RT in Neuronal Cells.";
RL ACS Infect. Dis. 5:932-948(2019).
RN [38]
RP INTERACTION WITH SARS-COV-2 ORF6 PROTEIN (MICROBIAL INFECTION).
RX PubMed=32979938; DOI=10.1016/j.celrep.2020.108234;
RA Xia H., Cao Z., Xie X., Zhang X., Chen J.Y., Wang H., Menachery V.D.,
RA Rajsbaum R., Shi P.Y.;
RT "Evasion of Type I Interferon by SARS-CoV-2.";
RL Cell Rep. 33:108234-108234(2020).
RN [39]
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 -!- SUBUNIT: (Microbial infection) Interacts with Zika virus RNA-directed
CC RNA polymerase NS5. {ECO:0000269|PubMed:30848123}.
CC -!- SUBUNIT: (Microbial infection) Interacts with SARS-CoV-2 ORF6 protein;
CC this interaction may inhibit IFN-beta production by blocking IRF3
CC nuclear translocation. {ECO:0000269|PubMed:32979938}.
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; Q14653: IRF3; NbExp=2; IntAct=EBI-349938, EBI-2650369;
CC P52292; P05412: JUN; NbExp=4; IntAct=EBI-349938, EBI-852823;
CC P52292; Q14974: KPNB1; NbExp=11; 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; Q16236: NFE2L2; NbExp=4; IntAct=EBI-349938, EBI-2007911;
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; P0DTC6: 6; Xeno; NbExp=2; IntAct=EBI-349938, EBI-25475897;
CC P52292; P03126: E6; Xeno; NbExp=2; IntAct=EBI-349938, EBI-1177242;
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.L; Xeno; NbExp=2; IntAct=EBI-349938, EBI-8469111;
CC P52292; K9N643: ORF4b; Xeno; NbExp=2; IntAct=EBI-349938, EBI-25641007;
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}.
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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 PDB; 7CRU; X-ray; 2.80 A; A/C=73-529.
DR PDB; 7N8J; X-ray; 3.20 A; A=76-529.
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 PDBsum; 7CRU; -.
DR PDBsum; 7N8J; -.
DR AlphaFoldDB; P52292; -.
DR SASBDB; P52292; -.
DR SMR; P52292; -.
DR BioGRID; 110036; 368.
DR ComplexPortal; CPX-1027; Importin complex, KPNA2 variant.
DR CORUM; P52292; -.
DR DIP; DIP-6205N; -.
DR IntAct; P52292; 181.
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 GlyGen; P52292; 1 site, 1 O-linked glycan (1 site).
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; 442 antibodies from 45 providers.
DR DNASU; 3838; -.
DR Ensembl; ENST00000330459.8; ENSP00000332455.3; ENSG00000182481.10.
DR Ensembl; ENST00000537025.6; ENSP00000438483.2; ENSG00000182481.10.
DR Ensembl; ENST00000579754.2; ENSP00000462331.2; ENSG00000182481.10.
DR Ensembl; ENST00000584026.6; ENSP00000463602.2; ENSG00000182481.10.
DR Ensembl; ENST00000677086.1; ENSP00000504655.1; ENSG00000182481.10.
DR Ensembl; ENST00000679078.1; ENSP00000504685.1; ENSG00000182481.10.
DR GeneID; 3838; -.
DR KEGG; hsa:3838; -.
DR MANE-Select; ENST00000330459.8; ENSP00000332455.3; NM_002266.4; NP_002257.1.
DR UCSC; uc002jgk.4; human.
DR CTD; 3838; -.
DR DisGeNET; 3838; -.
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 VEuPathDB; HostDB:ENSG00000182481; -.
DR eggNOG; KOG0166; Eukaryota.
DR GeneTree; ENSGT01050000244891; -.
DR HOGENOM; CLU_018084_6_1_1; -.
DR InParanoid; P52292; -.
DR OMA; CSELPIM; -.
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 Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR SignaLink; P52292; -.
DR SIGNOR; P52292; -.
DR BioGRID-ORCS; 3838; 91 hits in 1085 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 ventricular zone and 96 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:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043657; C:host cell; IEA:GOC.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0042564; C:NLS-dependent protein nuclear import complex; IPI:ComplexPortal.
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: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; 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; 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; Protein transport; Reference proteome; Repeat;
KW Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:22814378"
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 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 43..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 55..72
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:22814378"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|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:0007829|PDB:1QGK"
FT TURN 18..21
FT /evidence="ECO:0007829|PDB:1QGK"
FT HELIX 30..48
FT /evidence="ECO:0007829|PDB:1QGR"
FT HELIX 74..85
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 90..104
FT /evidence="ECO:0007829|PDB:4WV6"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:3FEY"
FT HELIX 112..117
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 121..128
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 134..148
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 152..160
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 163..170
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 176..190
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 194..202
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 206..213
FT /evidence="ECO:0007829|PDB:4WV6"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:5H43"
FT HELIX 218..220
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 223..236
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 246..259
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 265..278
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 283..290
FT /evidence="ECO:0007829|PDB:4WV6"
FT TURN 291..293
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 295..302
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 307..320
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 325..333
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 336..339
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 340..344
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 349..362
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 367..375
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 379..388
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 391..407
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 410..418
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 422..427
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 428..430
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 434..454
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 457..466
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 469..475
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 476..478
FT /evidence="ECO:0007829|PDB:4WV6"
FT HELIX 479..481
FT /evidence="ECO:0007829|PDB:3WPT"
FT HELIX 482..495
FT /evidence="ECO:0007829|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
