Full text data of KPNB1
KPNB1
(NTF97)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Importin subunit beta-1 (Importin-90; Karyopherin subunit beta-1; Nuclear factor p97; Pore targeting complex 97 kDa subunit; PTAC97)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Importin subunit beta-1 (Importin-90; Karyopherin subunit beta-1; Nuclear factor p97; Pore targeting complex 97 kDa subunit; PTAC97)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00001639
IPI00001639 Importin beta-1 subunit Zinc binding, nucelar pore, traslocation soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a expected molecular weight found in band found in band around 55 kDa
IPI00001639 Importin beta-1 subunit Zinc binding, nucelar pore, traslocation soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a expected molecular weight found in band found in band around 55 kDa
UniProt
Q14974
ID IMB1_HUMAN Reviewed; 876 AA.
AC Q14974; D3DTT3; Q14637; Q53XN2; Q96J27;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-MAY-2002, sequence version 2.
DT 22-JAN-2014, entry version 154.
DE RecName: Full=Importin subunit beta-1;
DE AltName: Full=Importin-90;
DE AltName: Full=Karyopherin subunit beta-1;
DE AltName: Full=Nuclear factor p97;
DE AltName: Full=Pore targeting complex 97 kDa subunit;
DE Short=PTAC97;
GN Name=KPNB1; Synonyms=NTF97;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHARACTERIZATION.
RC TISSUE=Brain;
RX PubMed=7615630; DOI=10.1083/jcb.130.2.265;
RA Chi N.C., Adam E.J.H., Adam S.A.;
RT "Sequence and characterization of cytoplasmic nuclear protein import
RT factor p97.";
RL J. Cell Biol. 130:265-274(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7627554; DOI=10.1016/S0960-9822(95)00079-0;
RA Goerlich D., Kostka S., Kraft R., Dingwall C., Laskey R.A.,
RA Hartmann E., Prehn S.;
RT "Two different subunits of importin cooperate to recognize nuclear
RT localization signals and bind them to the nuclear envelope.";
RL Curr. Biol. 5:383-392(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT vector.";
RL Submitted (AUG-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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Eye;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PARTIAL PROTEIN SEQUENCE, AND INTERACTION WITH AN IMPORTIN ALPHA
RP SUBUNIT.
RX PubMed=8617227;
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 [7]
RP PROTEIN SEQUENCE OF 1-9; 55-62 AND 192-206, ACETYLATION AT MET-1, AND
RP MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (MAY-2005) to UniProtKB.
RN [8]
RP RAN-GTP AND ALPHA SUBUNIT BINDING SITES.
RX PubMed=8692944; DOI=10.1073/pnas.93.14.7059;
RA Moroianu J., Blobel G., Radu A.;
RT "Nuclear protein import: Ran-GTP dissociates the karyopherin alphabeta
RT heterodimer by displacing alpha from an overlapping binding site on
RT beta.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:7059-7062(1996).
RN [9]
RP INTERACTION WITH HIV-1 REV AND TAT.
RX PubMed=9405152; DOI=10.1006/jmbi.1997.1420;
RA Henderson B.R., Percipalle P.;
RT "Interactions between HIV Rev and nuclear import and export factors:
RT the Rev nuclear localisation signal mediates specific binding to human
RT importin-beta.";
RL J. Mol. Biol. 274:693-707(1997).
RN [10]
RP INTERACTION WITH SNUPN.
RX PubMed=9670026; DOI=10.1093/emboj/17.14.4114;
RA Huber J., Cronshagen U., Kadokura M., Marshallsay C., Wada T.,
RA Sekine M., Luehrmann R.;
RT "Snurportin1, an m3G-cap-specific nuclear import receptor with a novel
RT domain structure.";
RL EMBO J. 17:4114-4126(1998).
RN [11]
RP FUNCTION, AND INTERACTION WITH RPL23A; RPS7; RPL5 AND IPO7.
RX PubMed=9687515; DOI=10.1093/emboj/17.15.4491;
RA Jaekel S., Goerlich D.;
RT "Importin beta, transportin, RanBP5 and RanBP7 mediate nuclear import
RT of ribosomal proteins in mammalian cells.";
RL EMBO J. 17:4491-4502(1998).
RN [12]
RP FUNCTION, AND INTERACTION WITH H1 HISTONE AND IPO7.
RX PubMed=10228156; DOI=10.1093/emboj/18.9.2411;
RA Jaekel S., Albig W., Kutay U., Bischoff F.R., Schwamborn K.,
RA Doenecke D., Goerlich D.;
RT "The importin beta/importin 7 heterodimer is a functional nuclear
RT import receptor for histone H1.";
RL EMBO J. 18:2411-2423(1999).
RN [13]
RP IDENTIFICATION IN AN EXPORT RECEPTOR COMPLEX, AND INTERACTION WITH
RP IPO7; SNUPN AND XPO1.
RX PubMed=10209022; DOI=10.1083/jcb.145.2.255;
RA Paraskeva E., Izaurralde E., Bischoff F.R., Huber J., Kutay U.,
RA Hartmann E., Luehrmann R., Goerlich D.;
RT "CRM1-mediated recycling of snurportin 1 to the cytoplasm.";
RL J. Cell Biol. 145:255-264(1999).
RN [14]
RP INTERACTION WITH HIV-1 REV.
RX PubMed=9891055;
RA Truant R., Cullen B.R.;
RT "The arginine-rich domains present in human immunodeficiency virus
RT type 1 Tat and Rev function as direct importin beta-dependent nuclear
RT localization signals.";
RL Mol. Cell. Biol. 19:1210-1217(1999).
RN [15]
RP INTERACTION WITH HTLV-1 REX.
RX PubMed=9891056;
RA Palmeri D., Malim M.H.;
RT "Importin beta can mediate the nuclear import of an arginine-rich
RT nuclear localization signal in the absence of importin alpha.";
RL Mol. Cell. Biol. 19:1218-1225(1999).
RN [16]
RP IDENTIFICATION IN AN IMPORT SNRNP COMPLEX.
RX PubMed=12095920; DOI=10.1093/hmg/11.15.1785;
RA Narayanan U., Ospina J.K., Frey M.R., Hebert M.D., Matera A.G.;
RT "SMN, the spinal muscular atrophy protein, forms a pre-import snRNP
RT complex with snurportin1 and importin beta.";
RL Hum. Mol. Genet. 11:1785-1795(2002).
RN [17]
RP INTERACTION WITH PRKCI, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11891849; DOI=10.1002/jcb.10101.abs;
RA White W.O., Seibenhener M.L., Wooten M.W.;
RT "Phosphorylation of tyrosine 256 facilitates nuclear import of
RT atypical protein kinase C.";
RL J. Cell. Biochem. 85:42-53(2002).
RN [18]
RP INTERACTION WITH SRY.
RX PubMed=12764225; DOI=10.1073/pnas.1137864100;
RA Harley V.R., Layfield S., Mitchell C.L., Forwood J.K., John A.P.,
RA Briggs L.J., McDowall S.G., Jans D.A.;
RT "Defective importin beta recognition and nuclear import of the sex-
RT determining factor SRY are associated with XY sex-reversing
RT mutations.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:7045-7050(2003).
RN [19]
RP INTERACTION WITH SRY.
RX PubMed=15297880; DOI=10.1038/sj.emboj.7600352;
RA Thevenet L., Mejean C., Moniot B., Bonneaud N., Galeotti N.,
RA Aldrian-Herrada G., Poulat F., Berta P., Benkirane M.,
RA Boizet-Bonhoure B.;
RT "Regulation of human SRY subcellular distribution by its
RT acetylation/deacetylation.";
RL EMBO J. 23:3336-3345(2004).
RN [20]
RP INTERACTION WITH HRSV PROTEIN M.
RX PubMed=16171404; DOI=10.1021/bi050701e;
RA Ghildyal R., Ho A., Wagstaff K.M., Dias M.M., Barton C.L., Jans P.,
RA Bardin P.G., Jans D.A.;
RT "Nuclear import of the respiratory syncytial virus matrix protein is
RT mediated by importin beta1 independent of importin alpha.";
RL Biochemistry 44:12887-12895(2005).
RN [21]
RP INTERACTION WITH SNAI1.
RX PubMed=15836774; DOI=10.1111/j.1365-2443.2005.00850.x;
RA Yamasaki H., Sekimoto T., Ohkubo T., Douchi T., Nagata Y., Ozawa M.,
RA Yoneda Y.;
RT "Zinc finger domain of Snail functions as a nuclear localization
RT signal for importin beta-mediated nuclear import pathway.";
RL Genes Cells 10:455-464(2005).
RN [22]
RP INTERACTION WITH HRSV PROTEIN M2-1.
RX PubMed=15629770; DOI=10.1016/j.virol.2004.10.031;
RA Reimers K., Buchholz K., Werchau H.;
RT "Respiratory syncytial virus M2-1 protein induces the activation of
RT nuclear factor kappa B.";
RL Virology 331:260-268(2005).
RN [23]
RP INTERACTION WITH HIV-1 REV.
RX PubMed=16704975; DOI=10.1074/jbc.M602189200;
RA Arnold M., Nath A., Hauber J., Kehlenbach R.H.;
RT "Multiple importins function as nuclear transport receptors for the
RT Rev protein of human immunodeficiency virus type 1.";
RL J. Biol. Chem. 281:20883-20890(2006).
RN [24]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-206 AND LYS-211, AND MASS
RP SPECTROMETRY.
RC TISSUE=Mammary cancer;
RX PubMed=17370265; DOI=10.1002/pmic.200600410;
RA Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.;
RT "Tryptic digestion of ubiquitin standards reveals an improved strategy
RT for identifying ubiquitinated proteins by mass spectrometry.";
RL Proteomics 7:868-874(2007).
RN [25]
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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12, AND MASS
RP SPECTROMETRY.
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 [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [28]
RP FUNCTION, AND 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
RT of C2H2 zinc finger transcription factors.";
RL J. Cell Sci. 122:1452-1460(2009).
RN [29]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-211; LYS-835 AND LYS-867,
RP AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [30]
RP INTERACTION WITH KPNA7.
RX PubMed=20701745; DOI=10.1186/1471-2121-11-63;
RA Kelley J.B., Talley A.M., Spencer A., Gioeli D., Paschal B.M.;
RT "Karyopherin alpha7 (KPNA7), a divergent member of the importin alpha
RT family of nuclear import receptors.";
RL BMC Cell Biol. 11:63-63(2010).
RN [31]
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.,
RA Buerckstuemmer T., 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 [32]
RP ADP-RIBOSYLATION, AND INTERACTION WITH PARP16.
RX PubMed=22701565; DOI=10.1371/journal.pone.0037352;
RA Di Paola S., Micaroni M., Di Tullio G., Buccione R., Di Girolamo M.;
RT "PARP16/ARTD15 is a novel endoplasmic-reticulum-associated mono-ADP-
RT ribosyltransferase that interacts with, and modifies karyopherin-
RT beta1.";
RL PLoS ONE 7:E37352-E37352(2012).
RN [33]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 2-459.
RX PubMed=10367892; DOI=10.1016/S0092-8674(00)80774-6;
RA Vetter I.R., Arndt A., Kutay U., Goerlich D., Wittinghofer A.;
RT "Structural view of the Ran-Importin beta interaction at 2.3 A
RT resolution.";
RL Cell 97:635-646(1999).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 3-442, AND MUTAGENESIS OF
RP ILE-178.
RX PubMed=10929717; DOI=10.1016/S0092-8674(00)00014-3;
RA Bayliss R., Littlewood T., Stewart M.;
RT "Structural basis for the interaction between FxFG nucleoporin repeats
RT and importin-beta in nuclear trafficking.";
RL Cell 102:99-108(2000).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 1-485.
RX PubMed=12504010; DOI=10.1016/S1097-2765(02)00727-X;
RA Cingolani G., Bednenko J., Gillespie M.T., Gerace L.;
RT "Molecular basis for the recognition of a nonclassical nuclear
RT localization signal by importin beta.";
RL Mol. Cell 10:1345-1353(2002).
CC -!- FUNCTION: Functions in nuclear protein import, either in
CC association with an adapter protein, like an importin-alpha
CC subunit, which binds to nuclear localization signals (NLS) in
CC cargo substrates, or by acting as autonomous nuclear transport
CC receptor. Acting autonomously, serves itself as NLS receptor.
CC Docking of the importin/substrate complex to the nuclear pore
CC complex (NPC) is mediated by KPNB1 through binding to nucleoporin
CC FxFG repeats and the complex is subsequently translocated through
CC the pore by an energy requiring, Ran-dependent mechanism. At the
CC nucleoplasmic side of the NPC, Ran binds to importin-beta and the
CC three components separate and importin-alpha and -beta are re-
CC exported from the nucleus to the cytoplasm where GTP hydrolysis
CC releases Ran from importin. The directionality of nuclear import
CC is thought to be conferred by an asymmetric distribution of the
CC GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.
CC Mediates autonomously the nuclear import of ribosomal proteins
CC RPL23A, RPS7 and RPL5. Binds to a beta-like import receptor
CC binding (BIB) domain of RPL23A. In association with IPO7 mediates
CC the nuclear import of H1 histone. In vitro, mediates nuclear
CC import of H2A, H2B, H3 and H4 histones. In case of HIV-1
CC infection, binds and mediates the nuclear import of HIV-1 Rev.
CC Imports SNAI1 and PRKCI into the nucleus.
CC -!- SUBUNIT: Forms a complex with an importin alpha subunit. Forms a
CC heterodimer with IPO7. Interacts with IPO7, SNUPN, RPL23A and
CC XPO1. The KPNB1/IPO7 heterodimer interacts with H1 histone.
CC Interacts with H2A, H2B, H3 and H4 histones (By similarity).
CC Component of an import snRNP complex composed of KPNB1, SNUPN,
CC SMN1 and ZNF259. Component of a nuclear export receptor complex
CC composed of KPNB1, Ran, SNUPN and XPO1. Binds to HIV-1 Rev and
CC Tat. Interacts with HTLV-1 Rex. Interacts with SRY. Interacts with
CC PRKCI/atypical protein kinase C iota. Interacts with human
CC respiratory syncytial virus (HRSV) protein M. Interacts with
CC KPNA7. Interacts with SNAI1 (via zinc fingers) and SNAI2 (via zinc
CC fingers).
CC -!- INTERACTION:
CC P04626:ERBB2; NbExp=14; IntAct=EBI-286758, EBI-641062;
CC P03101:L1 (xeno); NbExp=2; IntAct=EBI-286758, EBI-7362698;
CC P03107:L2 (xeno); NbExp=2; IntAct=EBI-286758, EBI-7362531;
CC Q8K4J6:Mkl1 (xeno); NbExp=5; IntAct=EBI-286758, EBI-8291665;
CC P14907:NSP1 (xeno); NbExp=2; IntAct=EBI-286758, EBI-12265;
CC Q16637-3:SMN2; NbExp=5; IntAct=EBI-286758, EBI-395447;
CC O75940:SMNDC1; NbExp=2; IntAct=EBI-286758, EBI-1052641;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus envelope.
CC -!- PTM: Mono-ADP-ribosylated by PARP16.
CC -!- SIMILARITY: Belongs to the importin beta family.
CC -!- SIMILARITY: Contains 8 HEAT repeats.
CC -!- SIMILARITY: Contains 1 importin N-terminal domain.
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DR EMBL; L39793; AAA82869.1; -; Genomic_DNA.
DR EMBL; L38951; AAC41763.1; -; mRNA.
DR EMBL; BT009797; AAP88799.1; -; mRNA.
DR EMBL; CH471109; EAW94807.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94808.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94810.1; -; Genomic_DNA.
DR EMBL; BC003572; AAH03572.1; -; mRNA.
DR EMBL; BC024045; AAH24045.1; -; mRNA.
DR EMBL; BC036703; AAH36703.1; -; mRNA.
DR PIR; I52907; I52907.
DR RefSeq; NP_001263382.1; NM_001276453.1.
DR RefSeq; NP_002256.2; NM_002265.5.
DR RefSeq; XP_005257398.1; XM_005257341.1.
DR UniGene; Hs.532793; -.
DR PDB; 1F59; X-ray; 2.80 A; A/B=1-442.
DR PDB; 1IBR; X-ray; 2.30 A; B/D=1-462.
DR PDB; 1M5N; X-ray; 2.90 A; S=1-485.
DR PDB; 1O6O; X-ray; 2.80 A; A/B/C=1-442.
DR PDB; 1O6P; X-ray; 2.80 A; A/B=1-442.
DR PDB; 1QGK; X-ray; 2.50 A; A=1-876.
DR PDB; 1QGR; X-ray; 2.30 A; A=1-876.
DR PDB; 2P8Q; X-ray; 2.35 A; A=1-876.
DR PDB; 2Q5D; X-ray; 3.20 A; A/B=1-876.
DR PDB; 2QNA; X-ray; 2.84 A; A=127-875.
DR PDB; 3LWW; X-ray; 3.15 A; A/C=1-876.
DR PDBsum; 1F59; -.
DR PDBsum; 1IBR; -.
DR PDBsum; 1M5N; -.
DR PDBsum; 1O6O; -.
DR PDBsum; 1O6P; -.
DR PDBsum; 1QGK; -.
DR PDBsum; 1QGR; -.
DR PDBsum; 2P8Q; -.
DR PDBsum; 2Q5D; -.
DR PDBsum; 2QNA; -.
DR PDBsum; 3LWW; -.
DR ProteinModelPortal; Q14974; -.
DR SMR; Q14974; 1-873.
DR DIP; DIP-6204N; -.
DR IntAct; Q14974; 53.
DR MINT; MINT-94095; -.
DR STRING; 9606.ENSP00000290158; -.
DR PhosphoSite; Q14974; -.
DR DMDM; 20981701; -.
DR PaxDb; Q14974; -.
DR PeptideAtlas; Q14974; -.
DR PRIDE; Q14974; -.
DR DNASU; 3837; -.
DR Ensembl; ENST00000290158; ENSP00000290158; ENSG00000108424.
DR GeneID; 3837; -.
DR KEGG; hsa:3837; -.
DR UCSC; uc002ilt.2; human.
DR CTD; 3837; -.
DR GeneCards; GC17P045727; -.
DR HGNC; HGNC:6400; KPNB1.
DR HPA; CAB034449; -.
DR HPA; HPA029878; -.
DR MIM; 602738; gene.
DR neXtProt; NX_Q14974; -.
DR PharmGKB; PA30191; -.
DR eggNOG; COG5215; -.
DR HOGENOM; HOG000204108; -.
DR HOVERGEN; HBG002369; -.
DR InParanoid; Q14974; -.
DR KO; K14293; -.
DR OMA; HQKQASL; -.
DR OrthoDB; EOG7GN2KZ; -.
DR PhylomeDB; Q14974; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q14974; -.
DR ChiTaRS; KPNB1; human.
DR EvolutionaryTrace; Q14974; -.
DR GeneWiki; KPNB1; -.
DR GenomeRNAi; 3837; -.
DR NextBio; 15083; -.
DR PRO; PR:Q14974; -.
DR ArrayExpress; Q14974; -.
DR Bgee; Q14974; -.
DR CleanEx; HS_KPNB1; -.
DR Genevestigator; Q14974; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005643; C:nuclear pore; TAS:ProtInc.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0008139; F:nuclear localization sequence binding; TAS:ProtInc.
DR GO; GO:0008565; F:protein transporter activity; IEA:Ensembl.
DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; TAS:Reactome.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0075733; P:intracellular transport of virus; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0006607; P:NLS-bearing protein import into nucleus; TAS:ProtInc.
DR GO; GO:0000060; P:protein import into nucleus, translocation; TAS:ProtInc.
DR GO; GO:0006610; P:ribosomal protein import into nucleus; IDA:UniProtKB.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR021133; HEAT_type_2.
DR InterPro; IPR001494; Importin-beta_N.
DR InterPro; IPR027140; KPNB1.
DR PANTHER; PTHR10527:SF8; PTHR10527:SF8; 1.
DR Pfam; PF00514; Arm; 1.
DR Pfam; PF03810; IBN_N; 1.
DR SMART; SM00913; IBN_N; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50077; HEAT_REPEAT; 1.
DR PROSITE; PS50166; IMPORTIN_B_NT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ADP-ribosylation; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Host-virus interaction;
KW Isopeptide bond; Nucleus; Phosphoprotein; Protein transport;
KW Reference proteome; Repeat; Transport; Ubl conjugation.
FT CHAIN 1 876 Importin subunit beta-1.
FT /FTId=PRO_0000120745.
FT DOMAIN 21 101 Importin N-terminal.
FT REPEAT 124 163 HEAT 1.
FT REPEAT 168 207 HEAT 2.
FT REPEAT 213 250 HEAT 3.
FT REPEAT 317 357 HEAT 4.
FT REPEAT 362 399 HEAT 5.
FT REPEAT 404 441 HEAT 6.
FT REPEAT 602 641 HEAT 7.
FT REPEAT 687 726 HEAT 8.
FT REGION 329 342 IAB-binding.
FT REGION 334 419 Ran-GTP binding.
FT COMPBIAS 337 341 Poly-Asp.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 12 12 Phosphoserine.
FT MOD_RES 211 211 N6-acetyllysine; alternate.
FT MOD_RES 835 835 N6-acetyllysine.
FT MOD_RES 867 867 N6-acetyllysine.
FT CROSSLNK 206 206 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT CROSSLNK 211 211 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate.
FT MUTAGEN 178 178 I->A: Largely reduced binding to FxFG
FT repeats and reduced nuclear import.
FT MUTAGEN 178 178 I->F,D: Loss of binding to FxFG repeats
FT and reduced nuclear import.
FT CONFLICT 97 97 Q -> H (in Ref. 1; AAA82869).
FT CONFLICT 200 200 N -> NA (in Ref. 6; AA sequence).
FT CONFLICT 863 863 T -> R (in Ref. 1; AAA82869).
FT HELIX 3 9
FT HELIX 15 45
FT HELIX 51 65
FT HELIX 70 81
FT HELIX 85 98
FT TURN 99 101
FT STRAND 104 106
FT HELIX 109 120
FT HELIX 121 123
FT HELIX 129 138
FT HELIX 144 160
FT HELIX 163 165
FT HELIX 167 169
FT HELIX 170 181
FT HELIX 188 201
FT TURN 202 205
FT HELIX 206 209
FT HELIX 212 225
FT STRAND 228 230
FT HELIX 231 247
FT HELIX 249 251
FT TURN 253 259
FT HELIX 260 269
FT HELIX 273 297
FT STRAND 303 305
FT HELIX 314 329
FT HELIX 330 332
FT STRAND 335 337
FT HELIX 344 358
FT TURN 359 362
FT HELIX 363 374
FT HELIX 380 392
FT STRAND 394 397
FT TURN 399 402
FT TURN 404 408
FT HELIX 409 415
FT HELIX 416 418
FT HELIX 422 438
FT HELIX 439 442
FT TURN 446 448
FT HELIX 449 457
FT HELIX 464 483
FT STRAND 487 493
FT TURN 500 502
FT HELIX 503 513
FT TURN 517 520
FT HELIX 521 523
FT HELIX 524 537
FT HELIX 541 543
FT HELIX 544 562
FT TURN 563 566
FT HELIX 573 592
FT STRAND 593 595
FT HELIX 597 601
FT HELIX 604 614
FT STRAND 619 622
FT HELIX 623 639
FT HELIX 640 646
FT HELIX 647 660
FT HELIX 664 681
FT HELIX 682 685
FT HELIX 686 700
FT STRAND 703 705
FT HELIX 707 709
FT HELIX 710 724
FT HELIX 725 731
FT HELIX 732 743
FT HELIX 752 777
FT STRAND 779 782
FT HELIX 785 789
FT HELIX 791 793
FT HELIX 794 805
FT HELIX 812 829
FT HELIX 832 838
FT HELIX 841 852
FT HELIX 856 873
SQ SEQUENCE 876 AA; 97170 MW; F3BB8B73E7E51639 CRC64;
MELITILEKT VSPDRLELEA AQKFLERAAV ENLPTFLVEL SRVLANPGNS QVARVAAGLQ
IKNSLTSKDP DIKAQYQQRW LAIDANARRE VKNYVLQTLG TETYRPSSAS QCVAGIACAE
IPVNQWPELI PQLVANVTNP NSTEHMKEST LEAIGYICQD IDPEQLQDKS NEILTAIIQG
MRKEEPSNNV KLAATNALLN SLEFTKANFD KESERHFIMQ VVCEATQCPD TRVRVAALQN
LVKIMSLYYQ YMETYMGPAL FAITIEAMKS DIDEVALQGI EFWSNVCDEE MDLAIEASEA
AEQGRPPEHT SKFYAKGALQ YLVPILTQTL TKQDENDDDD DWNPCKAAGV CLMLLATCCE
DDIVPHVLPF IKEHIKNPDW RYRDAAVMAF GCILEGPEPS QLKPLVIQAM PTLIELMKDP
SVVVRDTAAW TVGRICELLP EAAINDVYLA PLLQCLIEGL SAEPRVASNV CWAFSSLAEA
AYEAADVADD QEEPATYCLS SSFELIVQKL LETTDRPDGH QNNLRSSAYE SLMEIVKNSA
KDCYPAVQKT TLVIMERLQQ VLQMESHIQS TSDRIQFNDL QSLLCATLQN VLRKVQHQDA
LQISDVVMAS LLRMFQSTAG SGGVQEDALM AVSTLVEVLG GEFLKYMEAF KPFLGIGLKN
YAEYQVCLAA VGLVGDLCRA LQSNIIPFCD EVMQLLLENL GNENVHRSVK PQILSVFGDI
ALAIGGEFKK YLEVVLNTLQ QASQAQVDKS DYDMVDYLNE LRESCLEAYT GIVQGLKGDQ
ENVHPDVMLV QPRVEFILSF IDHIAGDEDH TDGVVACAAG LIGDLCTAFG KDVLKLVEAR
PMIHELLTEG RRSKTNKAKT LATWATKELR KLKNQA
//
ID IMB1_HUMAN Reviewed; 876 AA.
AC Q14974; D3DTT3; Q14637; Q53XN2; Q96J27;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-MAY-2002, sequence version 2.
DT 22-JAN-2014, entry version 154.
DE RecName: Full=Importin subunit beta-1;
DE AltName: Full=Importin-90;
DE AltName: Full=Karyopherin subunit beta-1;
DE AltName: Full=Nuclear factor p97;
DE AltName: Full=Pore targeting complex 97 kDa subunit;
DE Short=PTAC97;
GN Name=KPNB1; Synonyms=NTF97;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHARACTERIZATION.
RC TISSUE=Brain;
RX PubMed=7615630; DOI=10.1083/jcb.130.2.265;
RA Chi N.C., Adam E.J.H., Adam S.A.;
RT "Sequence and characterization of cytoplasmic nuclear protein import
RT factor p97.";
RL J. Cell Biol. 130:265-274(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7627554; DOI=10.1016/S0960-9822(95)00079-0;
RA Goerlich D., Kostka S., Kraft R., Dingwall C., Laskey R.A.,
RA Hartmann E., Prehn S.;
RT "Two different subunits of importin cooperate to recognize nuclear
RT localization signals and bind them to the nuclear envelope.";
RL Curr. Biol. 5:383-392(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT vector.";
RL Submitted (AUG-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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Eye;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PARTIAL PROTEIN SEQUENCE, AND INTERACTION WITH AN IMPORTIN ALPHA
RP SUBUNIT.
RX PubMed=8617227;
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 [7]
RP PROTEIN SEQUENCE OF 1-9; 55-62 AND 192-206, ACETYLATION AT MET-1, AND
RP MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (MAY-2005) to UniProtKB.
RN [8]
RP RAN-GTP AND ALPHA SUBUNIT BINDING SITES.
RX PubMed=8692944; DOI=10.1073/pnas.93.14.7059;
RA Moroianu J., Blobel G., Radu A.;
RT "Nuclear protein import: Ran-GTP dissociates the karyopherin alphabeta
RT heterodimer by displacing alpha from an overlapping binding site on
RT beta.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:7059-7062(1996).
RN [9]
RP INTERACTION WITH HIV-1 REV AND TAT.
RX PubMed=9405152; DOI=10.1006/jmbi.1997.1420;
RA Henderson B.R., Percipalle P.;
RT "Interactions between HIV Rev and nuclear import and export factors:
RT the Rev nuclear localisation signal mediates specific binding to human
RT importin-beta.";
RL J. Mol. Biol. 274:693-707(1997).
RN [10]
RP INTERACTION WITH SNUPN.
RX PubMed=9670026; DOI=10.1093/emboj/17.14.4114;
RA Huber J., Cronshagen U., Kadokura M., Marshallsay C., Wada T.,
RA Sekine M., Luehrmann R.;
RT "Snurportin1, an m3G-cap-specific nuclear import receptor with a novel
RT domain structure.";
RL EMBO J. 17:4114-4126(1998).
RN [11]
RP FUNCTION, AND INTERACTION WITH RPL23A; RPS7; RPL5 AND IPO7.
RX PubMed=9687515; DOI=10.1093/emboj/17.15.4491;
RA Jaekel S., Goerlich D.;
RT "Importin beta, transportin, RanBP5 and RanBP7 mediate nuclear import
RT of ribosomal proteins in mammalian cells.";
RL EMBO J. 17:4491-4502(1998).
RN [12]
RP FUNCTION, AND INTERACTION WITH H1 HISTONE AND IPO7.
RX PubMed=10228156; DOI=10.1093/emboj/18.9.2411;
RA Jaekel S., Albig W., Kutay U., Bischoff F.R., Schwamborn K.,
RA Doenecke D., Goerlich D.;
RT "The importin beta/importin 7 heterodimer is a functional nuclear
RT import receptor for histone H1.";
RL EMBO J. 18:2411-2423(1999).
RN [13]
RP IDENTIFICATION IN AN EXPORT RECEPTOR COMPLEX, AND INTERACTION WITH
RP IPO7; SNUPN AND XPO1.
RX PubMed=10209022; DOI=10.1083/jcb.145.2.255;
RA Paraskeva E., Izaurralde E., Bischoff F.R., Huber J., Kutay U.,
RA Hartmann E., Luehrmann R., Goerlich D.;
RT "CRM1-mediated recycling of snurportin 1 to the cytoplasm.";
RL J. Cell Biol. 145:255-264(1999).
RN [14]
RP INTERACTION WITH HIV-1 REV.
RX PubMed=9891055;
RA Truant R., Cullen B.R.;
RT "The arginine-rich domains present in human immunodeficiency virus
RT type 1 Tat and Rev function as direct importin beta-dependent nuclear
RT localization signals.";
RL Mol. Cell. Biol. 19:1210-1217(1999).
RN [15]
RP INTERACTION WITH HTLV-1 REX.
RX PubMed=9891056;
RA Palmeri D., Malim M.H.;
RT "Importin beta can mediate the nuclear import of an arginine-rich
RT nuclear localization signal in the absence of importin alpha.";
RL Mol. Cell. Biol. 19:1218-1225(1999).
RN [16]
RP IDENTIFICATION IN AN IMPORT SNRNP COMPLEX.
RX PubMed=12095920; DOI=10.1093/hmg/11.15.1785;
RA Narayanan U., Ospina J.K., Frey M.R., Hebert M.D., Matera A.G.;
RT "SMN, the spinal muscular atrophy protein, forms a pre-import snRNP
RT complex with snurportin1 and importin beta.";
RL Hum. Mol. Genet. 11:1785-1795(2002).
RN [17]
RP INTERACTION WITH PRKCI, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11891849; DOI=10.1002/jcb.10101.abs;
RA White W.O., Seibenhener M.L., Wooten M.W.;
RT "Phosphorylation of tyrosine 256 facilitates nuclear import of
RT atypical protein kinase C.";
RL J. Cell. Biochem. 85:42-53(2002).
RN [18]
RP INTERACTION WITH SRY.
RX PubMed=12764225; DOI=10.1073/pnas.1137864100;
RA Harley V.R., Layfield S., Mitchell C.L., Forwood J.K., John A.P.,
RA Briggs L.J., McDowall S.G., Jans D.A.;
RT "Defective importin beta recognition and nuclear import of the sex-
RT determining factor SRY are associated with XY sex-reversing
RT mutations.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:7045-7050(2003).
RN [19]
RP INTERACTION WITH SRY.
RX PubMed=15297880; DOI=10.1038/sj.emboj.7600352;
RA Thevenet L., Mejean C., Moniot B., Bonneaud N., Galeotti N.,
RA Aldrian-Herrada G., Poulat F., Berta P., Benkirane M.,
RA Boizet-Bonhoure B.;
RT "Regulation of human SRY subcellular distribution by its
RT acetylation/deacetylation.";
RL EMBO J. 23:3336-3345(2004).
RN [20]
RP INTERACTION WITH HRSV PROTEIN M.
RX PubMed=16171404; DOI=10.1021/bi050701e;
RA Ghildyal R., Ho A., Wagstaff K.M., Dias M.M., Barton C.L., Jans P.,
RA Bardin P.G., Jans D.A.;
RT "Nuclear import of the respiratory syncytial virus matrix protein is
RT mediated by importin beta1 independent of importin alpha.";
RL Biochemistry 44:12887-12895(2005).
RN [21]
RP INTERACTION WITH SNAI1.
RX PubMed=15836774; DOI=10.1111/j.1365-2443.2005.00850.x;
RA Yamasaki H., Sekimoto T., Ohkubo T., Douchi T., Nagata Y., Ozawa M.,
RA Yoneda Y.;
RT "Zinc finger domain of Snail functions as a nuclear localization
RT signal for importin beta-mediated nuclear import pathway.";
RL Genes Cells 10:455-464(2005).
RN [22]
RP INTERACTION WITH HRSV PROTEIN M2-1.
RX PubMed=15629770; DOI=10.1016/j.virol.2004.10.031;
RA Reimers K., Buchholz K., Werchau H.;
RT "Respiratory syncytial virus M2-1 protein induces the activation of
RT nuclear factor kappa B.";
RL Virology 331:260-268(2005).
RN [23]
RP INTERACTION WITH HIV-1 REV.
RX PubMed=16704975; DOI=10.1074/jbc.M602189200;
RA Arnold M., Nath A., Hauber J., Kehlenbach R.H.;
RT "Multiple importins function as nuclear transport receptors for the
RT Rev protein of human immunodeficiency virus type 1.";
RL J. Biol. Chem. 281:20883-20890(2006).
RN [24]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-206 AND LYS-211, AND MASS
RP SPECTROMETRY.
RC TISSUE=Mammary cancer;
RX PubMed=17370265; DOI=10.1002/pmic.200600410;
RA Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.;
RT "Tryptic digestion of ubiquitin standards reveals an improved strategy
RT for identifying ubiquitinated proteins by mass spectrometry.";
RL Proteomics 7:868-874(2007).
RN [25]
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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12, AND MASS
RP SPECTROMETRY.
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 [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [28]
RP FUNCTION, AND 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
RT of C2H2 zinc finger transcription factors.";
RL J. Cell Sci. 122:1452-1460(2009).
RN [29]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-211; LYS-835 AND LYS-867,
RP AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [30]
RP INTERACTION WITH KPNA7.
RX PubMed=20701745; DOI=10.1186/1471-2121-11-63;
RA Kelley J.B., Talley A.M., Spencer A., Gioeli D., Paschal B.M.;
RT "Karyopherin alpha7 (KPNA7), a divergent member of the importin alpha
RT family of nuclear import receptors.";
RL BMC Cell Biol. 11:63-63(2010).
RN [31]
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.,
RA Buerckstuemmer T., 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 [32]
RP ADP-RIBOSYLATION, AND INTERACTION WITH PARP16.
RX PubMed=22701565; DOI=10.1371/journal.pone.0037352;
RA Di Paola S., Micaroni M., Di Tullio G., Buccione R., Di Girolamo M.;
RT "PARP16/ARTD15 is a novel endoplasmic-reticulum-associated mono-ADP-
RT ribosyltransferase that interacts with, and modifies karyopherin-
RT beta1.";
RL PLoS ONE 7:E37352-E37352(2012).
RN [33]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 2-459.
RX PubMed=10367892; DOI=10.1016/S0092-8674(00)80774-6;
RA Vetter I.R., Arndt A., Kutay U., Goerlich D., Wittinghofer A.;
RT "Structural view of the Ran-Importin beta interaction at 2.3 A
RT resolution.";
RL Cell 97:635-646(1999).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 3-442, AND MUTAGENESIS OF
RP ILE-178.
RX PubMed=10929717; DOI=10.1016/S0092-8674(00)00014-3;
RA Bayliss R., Littlewood T., Stewart M.;
RT "Structural basis for the interaction between FxFG nucleoporin repeats
RT and importin-beta in nuclear trafficking.";
RL Cell 102:99-108(2000).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 1-485.
RX PubMed=12504010; DOI=10.1016/S1097-2765(02)00727-X;
RA Cingolani G., Bednenko J., Gillespie M.T., Gerace L.;
RT "Molecular basis for the recognition of a nonclassical nuclear
RT localization signal by importin beta.";
RL Mol. Cell 10:1345-1353(2002).
CC -!- FUNCTION: Functions in nuclear protein import, either in
CC association with an adapter protein, like an importin-alpha
CC subunit, which binds to nuclear localization signals (NLS) in
CC cargo substrates, or by acting as autonomous nuclear transport
CC receptor. Acting autonomously, serves itself as NLS receptor.
CC Docking of the importin/substrate complex to the nuclear pore
CC complex (NPC) is mediated by KPNB1 through binding to nucleoporin
CC FxFG repeats and the complex is subsequently translocated through
CC the pore by an energy requiring, Ran-dependent mechanism. At the
CC nucleoplasmic side of the NPC, Ran binds to importin-beta and the
CC three components separate and importin-alpha and -beta are re-
CC exported from the nucleus to the cytoplasm where GTP hydrolysis
CC releases Ran from importin. The directionality of nuclear import
CC is thought to be conferred by an asymmetric distribution of the
CC GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.
CC Mediates autonomously the nuclear import of ribosomal proteins
CC RPL23A, RPS7 and RPL5. Binds to a beta-like import receptor
CC binding (BIB) domain of RPL23A. In association with IPO7 mediates
CC the nuclear import of H1 histone. In vitro, mediates nuclear
CC import of H2A, H2B, H3 and H4 histones. In case of HIV-1
CC infection, binds and mediates the nuclear import of HIV-1 Rev.
CC Imports SNAI1 and PRKCI into the nucleus.
CC -!- SUBUNIT: Forms a complex with an importin alpha subunit. Forms a
CC heterodimer with IPO7. Interacts with IPO7, SNUPN, RPL23A and
CC XPO1. The KPNB1/IPO7 heterodimer interacts with H1 histone.
CC Interacts with H2A, H2B, H3 and H4 histones (By similarity).
CC Component of an import snRNP complex composed of KPNB1, SNUPN,
CC SMN1 and ZNF259. Component of a nuclear export receptor complex
CC composed of KPNB1, Ran, SNUPN and XPO1. Binds to HIV-1 Rev and
CC Tat. Interacts with HTLV-1 Rex. Interacts with SRY. Interacts with
CC PRKCI/atypical protein kinase C iota. Interacts with human
CC respiratory syncytial virus (HRSV) protein M. Interacts with
CC KPNA7. Interacts with SNAI1 (via zinc fingers) and SNAI2 (via zinc
CC fingers).
CC -!- INTERACTION:
CC P04626:ERBB2; NbExp=14; IntAct=EBI-286758, EBI-641062;
CC P03101:L1 (xeno); NbExp=2; IntAct=EBI-286758, EBI-7362698;
CC P03107:L2 (xeno); NbExp=2; IntAct=EBI-286758, EBI-7362531;
CC Q8K4J6:Mkl1 (xeno); NbExp=5; IntAct=EBI-286758, EBI-8291665;
CC P14907:NSP1 (xeno); NbExp=2; IntAct=EBI-286758, EBI-12265;
CC Q16637-3:SMN2; NbExp=5; IntAct=EBI-286758, EBI-395447;
CC O75940:SMNDC1; NbExp=2; IntAct=EBI-286758, EBI-1052641;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus envelope.
CC -!- PTM: Mono-ADP-ribosylated by PARP16.
CC -!- SIMILARITY: Belongs to the importin beta family.
CC -!- SIMILARITY: Contains 8 HEAT repeats.
CC -!- SIMILARITY: Contains 1 importin N-terminal domain.
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DR EMBL; L39793; AAA82869.1; -; Genomic_DNA.
DR EMBL; L38951; AAC41763.1; -; mRNA.
DR EMBL; BT009797; AAP88799.1; -; mRNA.
DR EMBL; CH471109; EAW94807.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94808.1; -; Genomic_DNA.
DR EMBL; CH471109; EAW94810.1; -; Genomic_DNA.
DR EMBL; BC003572; AAH03572.1; -; mRNA.
DR EMBL; BC024045; AAH24045.1; -; mRNA.
DR EMBL; BC036703; AAH36703.1; -; mRNA.
DR PIR; I52907; I52907.
DR RefSeq; NP_001263382.1; NM_001276453.1.
DR RefSeq; NP_002256.2; NM_002265.5.
DR RefSeq; XP_005257398.1; XM_005257341.1.
DR UniGene; Hs.532793; -.
DR PDB; 1F59; X-ray; 2.80 A; A/B=1-442.
DR PDB; 1IBR; X-ray; 2.30 A; B/D=1-462.
DR PDB; 1M5N; X-ray; 2.90 A; S=1-485.
DR PDB; 1O6O; X-ray; 2.80 A; A/B/C=1-442.
DR PDB; 1O6P; X-ray; 2.80 A; A/B=1-442.
DR PDB; 1QGK; X-ray; 2.50 A; A=1-876.
DR PDB; 1QGR; X-ray; 2.30 A; A=1-876.
DR PDB; 2P8Q; X-ray; 2.35 A; A=1-876.
DR PDB; 2Q5D; X-ray; 3.20 A; A/B=1-876.
DR PDB; 2QNA; X-ray; 2.84 A; A=127-875.
DR PDB; 3LWW; X-ray; 3.15 A; A/C=1-876.
DR PDBsum; 1F59; -.
DR PDBsum; 1IBR; -.
DR PDBsum; 1M5N; -.
DR PDBsum; 1O6O; -.
DR PDBsum; 1O6P; -.
DR PDBsum; 1QGK; -.
DR PDBsum; 1QGR; -.
DR PDBsum; 2P8Q; -.
DR PDBsum; 2Q5D; -.
DR PDBsum; 2QNA; -.
DR PDBsum; 3LWW; -.
DR ProteinModelPortal; Q14974; -.
DR SMR; Q14974; 1-873.
DR DIP; DIP-6204N; -.
DR IntAct; Q14974; 53.
DR MINT; MINT-94095; -.
DR STRING; 9606.ENSP00000290158; -.
DR PhosphoSite; Q14974; -.
DR DMDM; 20981701; -.
DR PaxDb; Q14974; -.
DR PeptideAtlas; Q14974; -.
DR PRIDE; Q14974; -.
DR DNASU; 3837; -.
DR Ensembl; ENST00000290158; ENSP00000290158; ENSG00000108424.
DR GeneID; 3837; -.
DR KEGG; hsa:3837; -.
DR UCSC; uc002ilt.2; human.
DR CTD; 3837; -.
DR GeneCards; GC17P045727; -.
DR HGNC; HGNC:6400; KPNB1.
DR HPA; CAB034449; -.
DR HPA; HPA029878; -.
DR MIM; 602738; gene.
DR neXtProt; NX_Q14974; -.
DR PharmGKB; PA30191; -.
DR eggNOG; COG5215; -.
DR HOGENOM; HOG000204108; -.
DR HOVERGEN; HBG002369; -.
DR InParanoid; Q14974; -.
DR KO; K14293; -.
DR OMA; HQKQASL; -.
DR OrthoDB; EOG7GN2KZ; -.
DR PhylomeDB; Q14974; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q14974; -.
DR ChiTaRS; KPNB1; human.
DR EvolutionaryTrace; Q14974; -.
DR GeneWiki; KPNB1; -.
DR GenomeRNAi; 3837; -.
DR NextBio; 15083; -.
DR PRO; PR:Q14974; -.
DR ArrayExpress; Q14974; -.
DR Bgee; Q14974; -.
DR CleanEx; HS_KPNB1; -.
DR Genevestigator; Q14974; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005643; C:nuclear pore; TAS:ProtInc.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0008139; F:nuclear localization sequence binding; TAS:ProtInc.
DR GO; GO:0008565; F:protein transporter activity; IEA:Ensembl.
DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; TAS:Reactome.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0075733; P:intracellular transport of virus; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0006607; P:NLS-bearing protein import into nucleus; TAS:ProtInc.
DR GO; GO:0000060; P:protein import into nucleus, translocation; TAS:ProtInc.
DR GO; GO:0006610; P:ribosomal protein import into nucleus; IDA:UniProtKB.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR021133; HEAT_type_2.
DR InterPro; IPR001494; Importin-beta_N.
DR InterPro; IPR027140; KPNB1.
DR PANTHER; PTHR10527:SF8; PTHR10527:SF8; 1.
DR Pfam; PF00514; Arm; 1.
DR Pfam; PF03810; IBN_N; 1.
DR SMART; SM00913; IBN_N; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50077; HEAT_REPEAT; 1.
DR PROSITE; PS50166; IMPORTIN_B_NT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ADP-ribosylation; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Host-virus interaction;
KW Isopeptide bond; Nucleus; Phosphoprotein; Protein transport;
KW Reference proteome; Repeat; Transport; Ubl conjugation.
FT CHAIN 1 876 Importin subunit beta-1.
FT /FTId=PRO_0000120745.
FT DOMAIN 21 101 Importin N-terminal.
FT REPEAT 124 163 HEAT 1.
FT REPEAT 168 207 HEAT 2.
FT REPEAT 213 250 HEAT 3.
FT REPEAT 317 357 HEAT 4.
FT REPEAT 362 399 HEAT 5.
FT REPEAT 404 441 HEAT 6.
FT REPEAT 602 641 HEAT 7.
FT REPEAT 687 726 HEAT 8.
FT REGION 329 342 IAB-binding.
FT REGION 334 419 Ran-GTP binding.
FT COMPBIAS 337 341 Poly-Asp.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 12 12 Phosphoserine.
FT MOD_RES 211 211 N6-acetyllysine; alternate.
FT MOD_RES 835 835 N6-acetyllysine.
FT MOD_RES 867 867 N6-acetyllysine.
FT CROSSLNK 206 206 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT CROSSLNK 211 211 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate.
FT MUTAGEN 178 178 I->A: Largely reduced binding to FxFG
FT repeats and reduced nuclear import.
FT MUTAGEN 178 178 I->F,D: Loss of binding to FxFG repeats
FT and reduced nuclear import.
FT CONFLICT 97 97 Q -> H (in Ref. 1; AAA82869).
FT CONFLICT 200 200 N -> NA (in Ref. 6; AA sequence).
FT CONFLICT 863 863 T -> R (in Ref. 1; AAA82869).
FT HELIX 3 9
FT HELIX 15 45
FT HELIX 51 65
FT HELIX 70 81
FT HELIX 85 98
FT TURN 99 101
FT STRAND 104 106
FT HELIX 109 120
FT HELIX 121 123
FT HELIX 129 138
FT HELIX 144 160
FT HELIX 163 165
FT HELIX 167 169
FT HELIX 170 181
FT HELIX 188 201
FT TURN 202 205
FT HELIX 206 209
FT HELIX 212 225
FT STRAND 228 230
FT HELIX 231 247
FT HELIX 249 251
FT TURN 253 259
FT HELIX 260 269
FT HELIX 273 297
FT STRAND 303 305
FT HELIX 314 329
FT HELIX 330 332
FT STRAND 335 337
FT HELIX 344 358
FT TURN 359 362
FT HELIX 363 374
FT HELIX 380 392
FT STRAND 394 397
FT TURN 399 402
FT TURN 404 408
FT HELIX 409 415
FT HELIX 416 418
FT HELIX 422 438
FT HELIX 439 442
FT TURN 446 448
FT HELIX 449 457
FT HELIX 464 483
FT STRAND 487 493
FT TURN 500 502
FT HELIX 503 513
FT TURN 517 520
FT HELIX 521 523
FT HELIX 524 537
FT HELIX 541 543
FT HELIX 544 562
FT TURN 563 566
FT HELIX 573 592
FT STRAND 593 595
FT HELIX 597 601
FT HELIX 604 614
FT STRAND 619 622
FT HELIX 623 639
FT HELIX 640 646
FT HELIX 647 660
FT HELIX 664 681
FT HELIX 682 685
FT HELIX 686 700
FT STRAND 703 705
FT HELIX 707 709
FT HELIX 710 724
FT HELIX 725 731
FT HELIX 732 743
FT HELIX 752 777
FT STRAND 779 782
FT HELIX 785 789
FT HELIX 791 793
FT HELIX 794 805
FT HELIX 812 829
FT HELIX 832 838
FT HELIX 841 852
FT HELIX 856 873
SQ SEQUENCE 876 AA; 97170 MW; F3BB8B73E7E51639 CRC64;
MELITILEKT VSPDRLELEA AQKFLERAAV ENLPTFLVEL SRVLANPGNS QVARVAAGLQ
IKNSLTSKDP DIKAQYQQRW LAIDANARRE VKNYVLQTLG TETYRPSSAS QCVAGIACAE
IPVNQWPELI PQLVANVTNP NSTEHMKEST LEAIGYICQD IDPEQLQDKS NEILTAIIQG
MRKEEPSNNV KLAATNALLN SLEFTKANFD KESERHFIMQ VVCEATQCPD TRVRVAALQN
LVKIMSLYYQ YMETYMGPAL FAITIEAMKS DIDEVALQGI EFWSNVCDEE MDLAIEASEA
AEQGRPPEHT SKFYAKGALQ YLVPILTQTL TKQDENDDDD DWNPCKAAGV CLMLLATCCE
DDIVPHVLPF IKEHIKNPDW RYRDAAVMAF GCILEGPEPS QLKPLVIQAM PTLIELMKDP
SVVVRDTAAW TVGRICELLP EAAINDVYLA PLLQCLIEGL SAEPRVASNV CWAFSSLAEA
AYEAADVADD QEEPATYCLS SSFELIVQKL LETTDRPDGH QNNLRSSAYE SLMEIVKNSA
KDCYPAVQKT TLVIMERLQQ VLQMESHIQS TSDRIQFNDL QSLLCATLQN VLRKVQHQDA
LQISDVVMAS LLRMFQSTAG SGGVQEDALM AVSTLVEVLG GEFLKYMEAF KPFLGIGLKN
YAEYQVCLAA VGLVGDLCRA LQSNIIPFCD EVMQLLLENL GNENVHRSVK PQILSVFGDI
ALAIGGEFKK YLEVVLNTLQ QASQAQVDKS DYDMVDYLNE LRESCLEAYT GIVQGLKGDQ
ENVHPDVMLV QPRVEFILSF IDHIAGDEDH TDGVVACAAG LIGDLCTAFG KDVLKLVEAR
PMIHELLTEG RRSKTNKAKT LATWATKELR KLKNQA
//
MIM
602738
*RECORD*
*FIELD* NO
602738
*FIELD* TI
*602738 KARYOPHERIN BETA-1; KPNB1
;;IMPORTIN BETA-1
*FIELD* TX
The import of proteins into the nucleus proceeds through the nuclear
read morepore complex. Cytoplasmic proteins with a nuclear localization signal
(NLS) bind to an importin-alpha (see 600685)/importin-beta heterodimer.
The trimeric complex docks to the cytoplasmic periphery of the nuclear
pore complex and is subsequently translocated through as a single
entity. The import reaction is terminated by the direct binding of RAN
(601179) to KPNB, which dissociates the importin heterodimer.
CLONING
Gorlich et al. (1995) purified a 90-kD subunit of importin (importin-90)
from Xenopus egg extracts and obtained a 188-amino acid partial protein
sequence from internal peptides. Using the partial amino acid sequence,
they isolated cDNAs encoding human importin-90, or KPNB1, from a HeLa
cell cDNA library. The sequence of the predicted 876-amino acid human
KPNB1 protein is 93% identical to the 188-amino acid partial sequence of
Xenopus importin-90. Gorlich et al. (1995) showed that Xenopus
importin-60 and importin-90 cooperate to form an import receptor that
distinguishes functional NLSs from nonfunctional ones and selectively
binds import substrates to the nuclear envelope. Independently, Chi et
al. (1995) identified cDNAs encoding human KPNB1. Based on the 97-kD
product of in vitro translation, they designated the protein p97. Using
a monoclonal antibody against bovine p97, Chi et al. (1995) localized
p97 to the cytoplasm and nuclear envelope of bovine kidney cells. These
authors found that recombinant human p97 binds zinc and that a bound
metal ion is required for nuclear envelope-binding activity. Kutay et
al. (1997) identified the regions of KPNB1 that interact with RAN,
importin-alpha, and the nuclear pore complex.
GENE FUNCTION
The guanosine triphosphatase Ran (601179) stimulates assembly of
microtubule asters and spindles in mitotic Xenopus egg extracts. A
carboxy-terminal region of the nuclear mitotic apparatus protein (NUMA;
164009), a nuclear protein required for organizing mitotic spindle
poles, mimics Ran's ability to induce asters. This NUMA fragment also
specifically interacted with importin-beta. Wiese et al. (2001) showed
that importin-beta is an inhibitor of microtubule aster assembly in
Xenopus egg extracts and that Ran regulates the interaction between
importin-beta and NUMA. Importin-beta therefore links NUMA to regulation
by Ran. Wiese et al. (2001) concluded that this suggests that similar
mechanisms regulate nuclear import during interphase and spindle
assembly during mitosis.
The survival of motor neuron (SMN1; 600354) protein is mutated in
patients with spinal muscular atrophy. SMN is part of a multiprotein
complex required for biogenesis of the Sm class of small nuclear
ribonucleoproteins (snRNPs). Following assembly of the Sm core domain,
snRNPs are transported to the nucleus via importin-beta. Sm snRNPs
contain a nuclear localization signal (NLS) consisting of a
2,2,7-trimethylguanosine (TMG) cap and the Sm core. Snurportin-1
(607902) is the adaptor protein that recognizes both the TMG cap and
importin-beta. Narayanan et al. (2002) reported that a mutant snurportin
construct lacking the importin-beta-binding (IBB) domain, but containing
an intact TMG cap-binding domain, localized primarily to the nucleus,
whereas full-length snurportin localized to the cytoplasm. Snurportin
interacted with SMN, Gemin3 (606168), Sm snRNPs, and importin-beta. In
the presence of ribonucleases, the interactions with SMN and Sm proteins
were abolished, suggesting that snRNAs may mediate this interplay. Cell
fractionation studies showed that snurportin bound preferentially to
cytoplasmic SMN complexes. Additionally, SMN directly interacted with
importin-beta in a GST-pull-down assay, suggesting that the SMN complex
may represent the Sm core NLS receptor predicted by previous studies.
The authors concluded that, following Sm protein assembly, the SMN
complex may persist until the final stages of cytoplasmic snRNP
maturation, and may provide somatic cell RNPs with an alternative NLS.
Using a library of endoribonuclease-prepared short interfering RNAs
(esiRNAs), Kittler et al. (2004) identified 37 genes required for cell
division, one of which was KPNB1. These 37 genes included several
splicing factors for which knockdown generates mitotic spindle defects.
In addition, a putative nuclear-export terminator was found to speed up
cell proliferation and mitotic progression after knockdown.
Caudron et al. (2005) reported that the spatial cues necessary for
microtubules to reproducibly self-organize during cell division are
provided by chromosome-mediated interaction gradients between the small
guanosine triphosphatase (GTPase) Ran and importin-beta. This produces
activity gradients that determine the spatial distribution of
microtubule nucleation and stabilization around chromosomes and that are
essential for the self-organization of microtubules into a bipolar
spindle.
Kalab et al. (2006) examined the Ran-importin-beta system in cells by
conventional and fluorescence lifetime microscopy using a biosensor,
termed Rango, that increases its fluorescence resonance energy transfer
signal when released from importin-beta by RanGTP. Rango is
predominantly free in mitotic cells, but is further liberated around
mitotic chromatin. In vitro experiments and modeling showed that this
localized increase of free cargoes corresponds to changes in RanGTP
concentration sufficient to stabilize microtubules in extracts. In
cells, the Ran-importin-beta-cargo gradient kinetically promotes spindle
formation but is largely dispensable once the spindle has been
established. Kalab et al. (2006) observed that the Ran system also
affects spindle pole formation and chromosome congression in vivo. Kalab
et al. (2006) concluded that conserved Ran-regulated pathways are
involved in multiple, parallel processes required for spindle function,
but that their relative contribution differs in chromatin- versus
centrosome/kinetochore-driven spindle assembly systems.
BIOCHEMICAL FEATURES
- Crystal Structure
Bayliss et al. (2000) described the crystal structure of a complex
between KPNB1 residues 1 to 442 and 5 tandem FxFG nucleoporin repeats
from yeast Nsp1.
Lee et al. (2003) showed the crystal structure of importin-beta
complexed with the active form of SREBP2 (600481). Importin-beta uses
characteristic long helices like a pair of chopsticks to interact with
an SREBP2 dimer. Importin-beta changes its conformation to reveal a
pseudo-2-fold symmetry on its surface structure so that it can
accommodate a symmetric dimer molecule.
To provide a basis for understanding the crucial cargo-release step of
nuclear import, Lee et al. (2005) presented the crystal structure of
full-length yeast importin-beta (Kap95) complexed with RanGTP (see
602362). Lee et al. (2005) identified a key interaction site where the
RanGTP switch I loop binds to the carboxy-terminal arch of Kap95. This
interaction produced a change in helicoidal pitch that locks Kap95 in a
conformation that cannot bind importin-alpha (see 600685) or cargo. Lee
et al. (2005) suggested an allosteric mechanism for nuclear import
complex disassembly by RanGTP.
MAPPING
By fluorescence in situ hybridization, Ayala-Madrigal et al. (2000)
mapped the KPNB1 gene to chromosome 17q21. By FISH, Matsuda et al.
(1996) mapped the mouse Kpnb1 gene to the proximal end of chromosome
11D.
*FIELD* RF
1. Ayala-Madrigal, M. L.; Doerr, S.; Ramirez-Duenas, M. L.; Hansmann,
I.: Assignment of KPNA4 and KPNB1 encoding karyopherin alpha 4 and
beta 1 to human chromosome bands 11q22 and 17q21 respectively, by
in situ hybridization. Cytogenet. Cell Genet. 89: 258-259, 2000.
2. Bayliss, R.; Littlewood, T.; Stewart, M.: Structural basis for
the interaction between FxFG nucleoporin repeats and importin-beta
in nuclear trafficking. Cell 102: 99-108, 2000.
3. Caudron, M.; Bunt, G.; Bastiaens, P.; Karsenti, E.: Spatial coordination
of spindle assembly by chromosome-mediated signaling gradients. Science 309:
1373-1376, 2005.
4. Chi, N. C.; Adam, E. J. H.; Adam, S. A.: Sequence and characterization
of cytoplasmic nuclear protein import factor p97. J. Cell Biol. 130:
265-274, 1995.
5. Gorlich, D.; Kostka, S.; Kraft, R.; Dingwall, C.; Laskey, R. A.;
Hartmann, E.; Prehn, S.: Two different subunits of importin cooperate
to recognize nuclear localization signals and bind them to the nuclear
envelope. Curr. Biol. 5: 383-392, 1995.
6. Kalab, P.; Pralle, A.; Isacoff, E. Y.; Heald, R.; Weis, K.: Analysis
of a RanGTP-regulated gradient in mitotic somatic cells. Nature 440:
697-701, 2006.
7. Kittler, R.; Putz, G.; Pelletier, L.; Poser, I.; Heninger, A.-K.;
Drechsel, D.; Fischer, S.; Konstantinova, I.; Habermann, B.; Grabner,
H.; Yaspo, M.-L.; Himmelbauer, H.; Korn, B.; Neugebauer, K.; Pisabarro,
M. T.; Buchholz, F.: An endoribonuclease-prepared siRNA screen in
human cells identifies genes essential for cell division. Nature 432:
1036-1040, 2004.
8. Kutay, U.; Izaurralde, E.; Bischoff, F. R.; Mattaj, I. W.; Gorlich,
D.: Dominant-negative mutants of importin-beta block multiple pathways
of import and export through the nuclear pore complex. EMBO J. 16:
1153-1163, 1997.
9. Lee, S. J.; Matsuura, Y.; Liu, S. M.; Stewart, M.: Structural
basis for nuclear import complex dissociation by RanGTP. (Letter) Nature 435:
693-696, 2005.
10. Lee, S. J.; Sekimoto, T.; Yamashita, E.; Nagoshi, E.; Nakagawa,
A.; Imamoto, N.; Yoshimura, M.; Sakai, H.; Chong, K. T.; Tsukihara,
T.; Yoneda, Y.: The structure of importin-beta bound to SREBP-2:
nuclear import of a transcription factor. Science 302: 1571-1575,
2003.
11. Matsuda, Y.; Hamatani, K.; Itoh, M.; Takahashi, E.; Araki, R.;
Abe, M.: Localization of the importin-beta gene to mouse chromosome
11D and rat chromosome 10q32.1. Genomics 36: 213-215, 1996.
12. Narayanan, U.; Ospina, J. K.; Frey, M. R.; Hebert, M. D.; Matera,
A. G.: SMN, the spinal muscular atrophy protein, forms a pre-import
snRNP complex with snurportin1 and importin beta. Hum. Molec. Genet. 11:
1785-1795, 2002.
13. Wiese, C.; Wilde, A.; Moore, M. S.; Adam, S. A.; Merdes, A.; Zheng,
Y.: Role of importin-beta in coupling Ran to downstream targets in
microtubule assembly. Science 291: 653-656, 2001.
*FIELD* CN
Ada Hamosh - updated: 5/26/2006
Ada Hamosh - updated: 10/10/2005
Ada Hamosh - updated: 6/15/2005
Ada Hamosh - updated: 3/8/2005
Ada Hamosh - updated: 12/3/2003
George E. Tiller - updated: 6/20/2003
Ada Hamosh - updated: 4/5/2001
Carol A. Bocchini - updated: 1/16/2001
Stylianos E. Antonarakis - updated: 8/4/2000
*FIELD* CD
Rebekah S. Rasooly: 6/22/1998
*FIELD* ED
alopez: 06/06/2006
terry: 5/26/2006
terry: 2/3/2006
alopez: 10/12/2005
terry: 10/10/2005
alopez: 6/16/2005
terry: 6/15/2005
alopez: 3/8/2005
alopez: 12/8/2003
terry: 12/3/2003
cwells: 6/20/2003
alopez: 4/6/2001
terry: 4/5/2001
mcapotos: 1/17/2001
carol: 1/16/2001
mgross: 8/4/2000
psherman: 6/22/1998
*RECORD*
*FIELD* NO
602738
*FIELD* TI
*602738 KARYOPHERIN BETA-1; KPNB1
;;IMPORTIN BETA-1
*FIELD* TX
The import of proteins into the nucleus proceeds through the nuclear
read morepore complex. Cytoplasmic proteins with a nuclear localization signal
(NLS) bind to an importin-alpha (see 600685)/importin-beta heterodimer.
The trimeric complex docks to the cytoplasmic periphery of the nuclear
pore complex and is subsequently translocated through as a single
entity. The import reaction is terminated by the direct binding of RAN
(601179) to KPNB, which dissociates the importin heterodimer.
CLONING
Gorlich et al. (1995) purified a 90-kD subunit of importin (importin-90)
from Xenopus egg extracts and obtained a 188-amino acid partial protein
sequence from internal peptides. Using the partial amino acid sequence,
they isolated cDNAs encoding human importin-90, or KPNB1, from a HeLa
cell cDNA library. The sequence of the predicted 876-amino acid human
KPNB1 protein is 93% identical to the 188-amino acid partial sequence of
Xenopus importin-90. Gorlich et al. (1995) showed that Xenopus
importin-60 and importin-90 cooperate to form an import receptor that
distinguishes functional NLSs from nonfunctional ones and selectively
binds import substrates to the nuclear envelope. Independently, Chi et
al. (1995) identified cDNAs encoding human KPNB1. Based on the 97-kD
product of in vitro translation, they designated the protein p97. Using
a monoclonal antibody against bovine p97, Chi et al. (1995) localized
p97 to the cytoplasm and nuclear envelope of bovine kidney cells. These
authors found that recombinant human p97 binds zinc and that a bound
metal ion is required for nuclear envelope-binding activity. Kutay et
al. (1997) identified the regions of KPNB1 that interact with RAN,
importin-alpha, and the nuclear pore complex.
GENE FUNCTION
The guanosine triphosphatase Ran (601179) stimulates assembly of
microtubule asters and spindles in mitotic Xenopus egg extracts. A
carboxy-terminal region of the nuclear mitotic apparatus protein (NUMA;
164009), a nuclear protein required for organizing mitotic spindle
poles, mimics Ran's ability to induce asters. This NUMA fragment also
specifically interacted with importin-beta. Wiese et al. (2001) showed
that importin-beta is an inhibitor of microtubule aster assembly in
Xenopus egg extracts and that Ran regulates the interaction between
importin-beta and NUMA. Importin-beta therefore links NUMA to regulation
by Ran. Wiese et al. (2001) concluded that this suggests that similar
mechanisms regulate nuclear import during interphase and spindle
assembly during mitosis.
The survival of motor neuron (SMN1; 600354) protein is mutated in
patients with spinal muscular atrophy. SMN is part of a multiprotein
complex required for biogenesis of the Sm class of small nuclear
ribonucleoproteins (snRNPs). Following assembly of the Sm core domain,
snRNPs are transported to the nucleus via importin-beta. Sm snRNPs
contain a nuclear localization signal (NLS) consisting of a
2,2,7-trimethylguanosine (TMG) cap and the Sm core. Snurportin-1
(607902) is the adaptor protein that recognizes both the TMG cap and
importin-beta. Narayanan et al. (2002) reported that a mutant snurportin
construct lacking the importin-beta-binding (IBB) domain, but containing
an intact TMG cap-binding domain, localized primarily to the nucleus,
whereas full-length snurportin localized to the cytoplasm. Snurportin
interacted with SMN, Gemin3 (606168), Sm snRNPs, and importin-beta. In
the presence of ribonucleases, the interactions with SMN and Sm proteins
were abolished, suggesting that snRNAs may mediate this interplay. Cell
fractionation studies showed that snurportin bound preferentially to
cytoplasmic SMN complexes. Additionally, SMN directly interacted with
importin-beta in a GST-pull-down assay, suggesting that the SMN complex
may represent the Sm core NLS receptor predicted by previous studies.
The authors concluded that, following Sm protein assembly, the SMN
complex may persist until the final stages of cytoplasmic snRNP
maturation, and may provide somatic cell RNPs with an alternative NLS.
Using a library of endoribonuclease-prepared short interfering RNAs
(esiRNAs), Kittler et al. (2004) identified 37 genes required for cell
division, one of which was KPNB1. These 37 genes included several
splicing factors for which knockdown generates mitotic spindle defects.
In addition, a putative nuclear-export terminator was found to speed up
cell proliferation and mitotic progression after knockdown.
Caudron et al. (2005) reported that the spatial cues necessary for
microtubules to reproducibly self-organize during cell division are
provided by chromosome-mediated interaction gradients between the small
guanosine triphosphatase (GTPase) Ran and importin-beta. This produces
activity gradients that determine the spatial distribution of
microtubule nucleation and stabilization around chromosomes and that are
essential for the self-organization of microtubules into a bipolar
spindle.
Kalab et al. (2006) examined the Ran-importin-beta system in cells by
conventional and fluorescence lifetime microscopy using a biosensor,
termed Rango, that increases its fluorescence resonance energy transfer
signal when released from importin-beta by RanGTP. Rango is
predominantly free in mitotic cells, but is further liberated around
mitotic chromatin. In vitro experiments and modeling showed that this
localized increase of free cargoes corresponds to changes in RanGTP
concentration sufficient to stabilize microtubules in extracts. In
cells, the Ran-importin-beta-cargo gradient kinetically promotes spindle
formation but is largely dispensable once the spindle has been
established. Kalab et al. (2006) observed that the Ran system also
affects spindle pole formation and chromosome congression in vivo. Kalab
et al. (2006) concluded that conserved Ran-regulated pathways are
involved in multiple, parallel processes required for spindle function,
but that their relative contribution differs in chromatin- versus
centrosome/kinetochore-driven spindle assembly systems.
BIOCHEMICAL FEATURES
- Crystal Structure
Bayliss et al. (2000) described the crystal structure of a complex
between KPNB1 residues 1 to 442 and 5 tandem FxFG nucleoporin repeats
from yeast Nsp1.
Lee et al. (2003) showed the crystal structure of importin-beta
complexed with the active form of SREBP2 (600481). Importin-beta uses
characteristic long helices like a pair of chopsticks to interact with
an SREBP2 dimer. Importin-beta changes its conformation to reveal a
pseudo-2-fold symmetry on its surface structure so that it can
accommodate a symmetric dimer molecule.
To provide a basis for understanding the crucial cargo-release step of
nuclear import, Lee et al. (2005) presented the crystal structure of
full-length yeast importin-beta (Kap95) complexed with RanGTP (see
602362). Lee et al. (2005) identified a key interaction site where the
RanGTP switch I loop binds to the carboxy-terminal arch of Kap95. This
interaction produced a change in helicoidal pitch that locks Kap95 in a
conformation that cannot bind importin-alpha (see 600685) or cargo. Lee
et al. (2005) suggested an allosteric mechanism for nuclear import
complex disassembly by RanGTP.
MAPPING
By fluorescence in situ hybridization, Ayala-Madrigal et al. (2000)
mapped the KPNB1 gene to chromosome 17q21. By FISH, Matsuda et al.
(1996) mapped the mouse Kpnb1 gene to the proximal end of chromosome
11D.
*FIELD* RF
1. Ayala-Madrigal, M. L.; Doerr, S.; Ramirez-Duenas, M. L.; Hansmann,
I.: Assignment of KPNA4 and KPNB1 encoding karyopherin alpha 4 and
beta 1 to human chromosome bands 11q22 and 17q21 respectively, by
in situ hybridization. Cytogenet. Cell Genet. 89: 258-259, 2000.
2. Bayliss, R.; Littlewood, T.; Stewart, M.: Structural basis for
the interaction between FxFG nucleoporin repeats and importin-beta
in nuclear trafficking. Cell 102: 99-108, 2000.
3. Caudron, M.; Bunt, G.; Bastiaens, P.; Karsenti, E.: Spatial coordination
of spindle assembly by chromosome-mediated signaling gradients. Science 309:
1373-1376, 2005.
4. Chi, N. C.; Adam, E. J. H.; Adam, S. A.: Sequence and characterization
of cytoplasmic nuclear protein import factor p97. J. Cell Biol. 130:
265-274, 1995.
5. Gorlich, D.; Kostka, S.; Kraft, R.; Dingwall, C.; Laskey, R. A.;
Hartmann, E.; Prehn, S.: Two different subunits of importin cooperate
to recognize nuclear localization signals and bind them to the nuclear
envelope. Curr. Biol. 5: 383-392, 1995.
6. Kalab, P.; Pralle, A.; Isacoff, E. Y.; Heald, R.; Weis, K.: Analysis
of a RanGTP-regulated gradient in mitotic somatic cells. Nature 440:
697-701, 2006.
7. Kittler, R.; Putz, G.; Pelletier, L.; Poser, I.; Heninger, A.-K.;
Drechsel, D.; Fischer, S.; Konstantinova, I.; Habermann, B.; Grabner,
H.; Yaspo, M.-L.; Himmelbauer, H.; Korn, B.; Neugebauer, K.; Pisabarro,
M. T.; Buchholz, F.: An endoribonuclease-prepared siRNA screen in
human cells identifies genes essential for cell division. Nature 432:
1036-1040, 2004.
8. Kutay, U.; Izaurralde, E.; Bischoff, F. R.; Mattaj, I. W.; Gorlich,
D.: Dominant-negative mutants of importin-beta block multiple pathways
of import and export through the nuclear pore complex. EMBO J. 16:
1153-1163, 1997.
9. Lee, S. J.; Matsuura, Y.; Liu, S. M.; Stewart, M.: Structural
basis for nuclear import complex dissociation by RanGTP. (Letter) Nature 435:
693-696, 2005.
10. Lee, S. J.; Sekimoto, T.; Yamashita, E.; Nagoshi, E.; Nakagawa,
A.; Imamoto, N.; Yoshimura, M.; Sakai, H.; Chong, K. T.; Tsukihara,
T.; Yoneda, Y.: The structure of importin-beta bound to SREBP-2:
nuclear import of a transcription factor. Science 302: 1571-1575,
2003.
11. Matsuda, Y.; Hamatani, K.; Itoh, M.; Takahashi, E.; Araki, R.;
Abe, M.: Localization of the importin-beta gene to mouse chromosome
11D and rat chromosome 10q32.1. Genomics 36: 213-215, 1996.
12. Narayanan, U.; Ospina, J. K.; Frey, M. R.; Hebert, M. D.; Matera,
A. G.: SMN, the spinal muscular atrophy protein, forms a pre-import
snRNP complex with snurportin1 and importin beta. Hum. Molec. Genet. 11:
1785-1795, 2002.
13. Wiese, C.; Wilde, A.; Moore, M. S.; Adam, S. A.; Merdes, A.; Zheng,
Y.: Role of importin-beta in coupling Ran to downstream targets in
microtubule assembly. Science 291: 653-656, 2001.
*FIELD* CN
Ada Hamosh - updated: 5/26/2006
Ada Hamosh - updated: 10/10/2005
Ada Hamosh - updated: 6/15/2005
Ada Hamosh - updated: 3/8/2005
Ada Hamosh - updated: 12/3/2003
George E. Tiller - updated: 6/20/2003
Ada Hamosh - updated: 4/5/2001
Carol A. Bocchini - updated: 1/16/2001
Stylianos E. Antonarakis - updated: 8/4/2000
*FIELD* CD
Rebekah S. Rasooly: 6/22/1998
*FIELD* ED
alopez: 06/06/2006
terry: 5/26/2006
terry: 2/3/2006
alopez: 10/12/2005
terry: 10/10/2005
alopez: 6/16/2005
terry: 6/15/2005
alopez: 3/8/2005
alopez: 12/8/2003
terry: 12/3/2003
cwells: 6/20/2003
alopez: 4/6/2001
terry: 4/5/2001
mcapotos: 1/17/2001
carol: 1/16/2001
mgross: 8/4/2000
psherman: 6/22/1998