Full text data of KPNA2
KPNA2
(RCH1, SRP1)
[Confidence: low (only semi-automatic identification from reviews)]
Importin subunit alpha-1 (Karyopherin subunit alpha-2; RAG cohort protein 1; SRP1-alpha)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Importin subunit alpha-1 (Karyopherin subunit alpha-2; RAG cohort protein 1; SRP1-alpha)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P52292
ID IMA1_HUMAN Reviewed; 529 AA.
AC P52292; B9EJD6; Q53YE3; Q9BRU5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 1.
DT 22-JAN-2014, entry version 165.
DE RecName: Full=Importin subunit alpha-1;
DE AltName: Full=Karyopherin subunit alpha-2;
DE AltName: Full=RAG cohort protein 1;
DE AltName: Full=SRP1-alpha;
GN Name=KPNA2; Synonyms=RCH1, SRP1;
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 [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
RT repeat on chromosome 17q23-q24 and mutation analysis in patients with
RT Russell-Silver syndrome.";
RL Hum. Genet. 109:479-486(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-157 AND
RP 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
RT 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.,
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-157 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
RT project: 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
RP AND 487-494, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2,
RP AND 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
RT recombination-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:
RT alpha 1 or alpha 2 subunit binds nuclear localization signal and beta
RT subunit 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;
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.
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
RT alpha 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
RT localized 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,
RT which 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
RT protein 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
RT multiple 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
RT apurinic/apyrimidinic 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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, AND MASS
RP SPECTROMETRY.
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
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [20]
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.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [21]
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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-490, 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 [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, 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 [24]
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
RT of C2H2 zinc finger transcription factors.";
RL J. Cell Sci. 122:1452-1460(2009).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, AND MASS
RP SPECTROMETRY.
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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-490, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [27]
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 [28]
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 [29]
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 [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-62, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, 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 [32]
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-
RT alpha.";
RL Nature 399:221-229(1999).
CC -!- FUNCTION: Functions in nuclear protein import as an adapter
CC protein for nuclear receptor KPNB1. Binds specifically and
CC directly to substrates containing either a simple or bipartite NLS
CC motif. Docking of the importin/substrate complex to the nuclear
CC pore complex (NPC) is mediated by KPNB1 through binding to
CC nucleoporin FxFG repeats and the complex is subsequently
CC translocated through the pore by an energy requiring, Ran-
CC dependent mechanism. At the nucleoplasmic side of the NPC, Ran
CC 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
CC between the cytoplasm and nucleus.
CC -!- SUBUNIT: Heterodimer; with KPNB1. Interacts with ANP32E (By
CC similarity). Component of a complex containing CSE1L, RAN and
CC KPNA2. Interacts directly with CSE1L. Interacts with HIV-1 Vpr and
CC PLAG1. Interacts with APEX1 (via N-terminus). Interacts with
CC ARL4A, CTNNBL1 and NBN. Interacts with SNAI1 (via zinc fingers)
CC and SNAI2 (via zinc fingers).
CC -!- INTERACTION:
CC P38398:BRCA1; NbExp=3; IntAct=EBI-349938, EBI-349905;
CC O96017:CHEK2; NbExp=3; IntAct=EBI-349938, EBI-1180783;
CC P05412:JUN; NbExp=2; IntAct=EBI-349938, EBI-852823;
CC P03101:L1 (xeno); NbExp=3; IntAct=EBI-349938, EBI-7362698;
CC P03107:L2 (xeno); NbExp=3; IntAct=EBI-349938, EBI-7362531;
CC Q6GQG6:npm2 (xeno); NbExp=2; IntAct=EBI-349938, EBI-8469111;
CC P46063:RECQL; NbExp=2; IntAct=EBI-349938, EBI-2823728;
CC P29034:S100A2; NbExp=5; IntAct=EBI-349938, EBI-752230;
CC P06703:S100A6; NbExp=3; IntAct=EBI-349938, EBI-352877;
CC Q9UH99:SUN2; NbExp=3; IntAct=EBI-349938, EBI-1044964;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously.
CC -!- DOMAIN: Consists of an N-terminal hydrophilic region, a
CC hydrophobic central region composed of 10 repeats, and a short
CC hydrophilic C-terminus. The N-terminal hydrophilic region contains
CC the importin beta binding domain (IBB domain), which is sufficient
CC for binding importin beta and essential for nuclear protein
CC import.
CC -!- DOMAIN: The IBB domain is thought to act as an intrasteric
CC autoregulatory sequence by interacting with the internal
CC autoinhibitory NLS. Binding of KPNB1 probably overlaps the
CC internal NLS and contributes to a high affinity for cytoplasmic
CC NLS-containing cargo substrates. After dissociation of the
CC importin/substrate complex in the nucleus the internal
CC autohibitory NLS contributes to a low affinity for nuclear NLS-
CC containing proteins (By similarity).
CC -!- DOMAIN: The major and minor NLS binding sites are mainly involved
CC in recognition of simple or bipartite NLS motifs. Structurally
CC located within in a helical surface groove they contain several
CC conserved Trp and Asn residues of the corresponding third helices
CC (H3) of ARM repeats which mainly contribute to binding (By
CC similarity).
CC -!- MASS SPECTROMETRY: Mass=57861.92; Method=MALDI; Range=1-529;
CC Source=PubMed:11840567;
CC -!- SIMILARITY: Belongs to the importin alpha family.
CC -!- SIMILARITY: Contains 10 ARM repeats.
CC -!- SIMILARITY: Contains 1 IBB domain.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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; BC146905; AAI46906.1; -; mRNA.
DR EMBL; U09559; AAA65700.1; -; mRNA.
DR PIR; A56516; A56516.
DR RefSeq; NP_002257.1; NM_002266.2.
DR RefSeq; XP_005257399.1; XM_005257342.1.
DR RefSeq; XP_005277833.1; XM_005277776.1.
DR UniGene; Hs.594238; -.
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; 4E4V; X-ray; 2.53 A; A/B=70-529.
DR PDBsum; 1EFX; -.
DR PDBsum; 1QGK; -.
DR PDBsum; 1QGR; -.
DR PDBsum; 3FEX; -.
DR PDBsum; 3FEY; -.
DR PDBsum; 4E4V; -.
DR ProteinModelPortal; P52292; -.
DR SMR; P52292; 11-499.
DR DIP; DIP-6205N; -.
DR IntAct; P52292; 73.
DR MINT; MINT-94121; -.
DR STRING; 9606.ENSP00000332455; -.
DR BindingDB; P52292; -.
DR ChEMBL; CHEMBL1741187; -.
DR PhosphoSite; P52292; -.
DR DMDM; 1708480; -.
DR SWISS-2DPAGE; P52292; -.
DR PaxDb; P52292; -.
DR PeptideAtlas; P52292; -.
DR PRIDE; P52292; -.
DR DNASU; 3838; -.
DR Ensembl; ENST00000330459; ENSP00000332455; ENSG00000182481.
DR Ensembl; ENST00000537025; ENSP00000438483; ENSG00000182481.
DR Ensembl; ENST00000571293; ENSP00000460119; ENSG00000262472.
DR Ensembl; ENST00000574083; ENSP00000460025; ENSG00000262472.
DR GeneID; 3838; -.
DR KEGG; hsa:3838; -.
DR UCSC; uc002jgk.3; human.
DR CTD; 3838; -.
DR GeneCards; GC17P066031; -.
DR HGNC; HGNC:6395; KPNA2.
DR HPA; CAB015460; -.
DR MIM; 600685; gene.
DR neXtProt; NX_P52292; -.
DR PharmGKB; PA30186; -.
DR eggNOG; COG5064; -.
DR HOGENOM; HOG000167616; -.
DR HOVERGEN; HBG001846; -.
DR InParanoid; P52292; -.
DR KO; K15043; -.
DR OMA; NETEKLC; -.
DR PhylomeDB; P52292; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P52292; -.
DR ChiTaRS; KPNA2; human.
DR EvolutionaryTrace; P52292; -.
DR GeneWiki; Karyopherin_alpha_2; -.
DR GenomeRNAi; 3838; -.
DR NextBio; 15087; -.
DR PRO; PR:P52292; -.
DR ArrayExpress; P52292; -.
DR Bgee; P52292; -.
DR CleanEx; HS_KPNA2; -.
DR Genevestigator; P52292; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0008139; F:nuclear localization sequence binding; IDA:UniProtKB.
DR GO; GO:0008565; F:protein transporter activity; IEA:InterPro.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0006259; P:DNA metabolic process; TAS:ProtInc.
DR GO; GO:0000085; P:mitotic G2 phase; TAS:ProtInc.
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; IDA:UniProtKB.
DR GO; GO:0000018; P:regulation of DNA recombination; TAS:ProtInc.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR002652; Importin-a_IBB.
DR InterPro; IPR024931; Importing_su_alpha.
DR Pfam; PF00514; Arm; 8.
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; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Host-virus interaction; Nucleus;
KW Phosphoprotein; Polymorphism; Protein transport; Reference proteome;
KW Repeat; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 529 Importin subunit alpha-1.
FT /FTId=PRO_0000120722.
FT DOMAIN 2 60 IBB.
FT REPEAT 71 111 ARM 1; truncated.
FT REPEAT 112 151 ARM 2.
FT REPEAT 152 193 ARM 3.
FT REPEAT 200 244 ARM 4.
FT REPEAT 246 282 ARM 5.
FT REPEAT 283 322 ARM 6.
FT REPEAT 325 364 ARM 7.
FT REPEAT 367 409 ARM 8.
FT REPEAT 410 456 ARM 9.
FT REPEAT 457 496 ARM 10; atypical.
FT REGION 142 238 NLS binding site (major) (By similarity).
FT REGION 315 403 NLS binding site (minor) (By similarity).
FT MOTIF 45 54 Nuclear localization signal (By
FT similarity).
FT COMPBIAS 28 31 Poly-Arg.
FT COMPBIAS 499 502 Poly-Glu.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 62 62 Phosphoserine.
FT MOD_RES 490 490 Phosphoserine.
FT VARIANT 157 157 A -> V (in dbSNP:rs17850032).
FT /FTId=VAR_067625.
FT VARIANT 165 165 P -> R (in dbSNP:rs11545989).
FT /FTId=VAR_013137.
FT VARIANT 365 365 G -> S (in dbSNP:rs1059558).
FT /FTId=VAR_067626.
FT VARIANT 430 430 T -> P (in dbSNP:rs1059538).
FT /FTId=VAR_014453.
FT VARIANT 453 453 K -> N (in dbSNP:rs17850031).
FT /FTId=VAR_067627.
FT HELIX 14 16
FT TURN 18 21
FT HELIX 30 48
FT HELIX 78 85
FT HELIX 90 104
FT STRAND 106 108
FT HELIX 112 117
FT HELIX 120 129
FT HELIX 134 147
FT HELIX 152 160
FT HELIX 163 170
FT HELIX 176 190
FT HELIX 194 202
FT HELIX 206 211
FT HELIX 218 220
FT HELIX 223 236
FT HELIX 246 259
FT HELIX 265 279
FT HELIX 283 291
FT HELIX 295 301
FT HELIX 307 320
FT HELIX 325 333
FT HELIX 336 344
FT HELIX 349 362
FT HELIX 367 375
FT HELIX 379 388
FT HELIX 391 407
FT HELIX 410 418
FT HELIX 422 427
FT HELIX 428 430
FT HELIX 434 453
FT HELIX 457 466
FT HELIX 469 475
FT HELIX 476 478
FT HELIX 482 495
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
//
ID IMA1_HUMAN Reviewed; 529 AA.
AC P52292; B9EJD6; Q53YE3; Q9BRU5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 1.
DT 22-JAN-2014, entry version 165.
DE RecName: Full=Importin subunit alpha-1;
DE AltName: Full=Karyopherin subunit alpha-2;
DE AltName: Full=RAG cohort protein 1;
DE AltName: Full=SRP1-alpha;
GN Name=KPNA2; Synonyms=RCH1, SRP1;
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 [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
RT repeat on chromosome 17q23-q24 and mutation analysis in patients with
RT Russell-Silver syndrome.";
RL Hum. Genet. 109:479-486(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-157 AND
RP 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
RT 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.,
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-157 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
RT project: 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
RP AND 487-494, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2,
RP AND 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
RT recombination-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:
RT alpha 1 or alpha 2 subunit binds nuclear localization signal and beta
RT subunit 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;
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.
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
RT alpha 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
RT localized 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,
RT which 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
RT protein 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
RT multiple 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
RT apurinic/apyrimidinic 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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, AND MASS
RP SPECTROMETRY.
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
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [20]
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.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [21]
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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-490, 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 [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, 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 [24]
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
RT of C2H2 zinc finger transcription factors.";
RL J. Cell Sci. 122:1452-1460(2009).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, AND MASS
RP SPECTROMETRY.
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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-490, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [27]
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 [28]
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 [29]
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 [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-62, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, 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 [32]
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-
RT alpha.";
RL Nature 399:221-229(1999).
CC -!- FUNCTION: Functions in nuclear protein import as an adapter
CC protein for nuclear receptor KPNB1. Binds specifically and
CC directly to substrates containing either a simple or bipartite NLS
CC motif. Docking of the importin/substrate complex to the nuclear
CC pore complex (NPC) is mediated by KPNB1 through binding to
CC nucleoporin FxFG repeats and the complex is subsequently
CC translocated through the pore by an energy requiring, Ran-
CC dependent mechanism. At the nucleoplasmic side of the NPC, Ran
CC 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
CC between the cytoplasm and nucleus.
CC -!- SUBUNIT: Heterodimer; with KPNB1. Interacts with ANP32E (By
CC similarity). Component of a complex containing CSE1L, RAN and
CC KPNA2. Interacts directly with CSE1L. Interacts with HIV-1 Vpr and
CC PLAG1. Interacts with APEX1 (via N-terminus). Interacts with
CC ARL4A, CTNNBL1 and NBN. Interacts with SNAI1 (via zinc fingers)
CC and SNAI2 (via zinc fingers).
CC -!- INTERACTION:
CC P38398:BRCA1; NbExp=3; IntAct=EBI-349938, EBI-349905;
CC O96017:CHEK2; NbExp=3; IntAct=EBI-349938, EBI-1180783;
CC P05412:JUN; NbExp=2; IntAct=EBI-349938, EBI-852823;
CC P03101:L1 (xeno); NbExp=3; IntAct=EBI-349938, EBI-7362698;
CC P03107:L2 (xeno); NbExp=3; IntAct=EBI-349938, EBI-7362531;
CC Q6GQG6:npm2 (xeno); NbExp=2; IntAct=EBI-349938, EBI-8469111;
CC P46063:RECQL; NbExp=2; IntAct=EBI-349938, EBI-2823728;
CC P29034:S100A2; NbExp=5; IntAct=EBI-349938, EBI-752230;
CC P06703:S100A6; NbExp=3; IntAct=EBI-349938, EBI-352877;
CC Q9UH99:SUN2; NbExp=3; IntAct=EBI-349938, EBI-1044964;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously.
CC -!- DOMAIN: Consists of an N-terminal hydrophilic region, a
CC hydrophobic central region composed of 10 repeats, and a short
CC hydrophilic C-terminus. The N-terminal hydrophilic region contains
CC the importin beta binding domain (IBB domain), which is sufficient
CC for binding importin beta and essential for nuclear protein
CC import.
CC -!- DOMAIN: The IBB domain is thought to act as an intrasteric
CC autoregulatory sequence by interacting with the internal
CC autoinhibitory NLS. Binding of KPNB1 probably overlaps the
CC internal NLS and contributes to a high affinity for cytoplasmic
CC NLS-containing cargo substrates. After dissociation of the
CC importin/substrate complex in the nucleus the internal
CC autohibitory NLS contributes to a low affinity for nuclear NLS-
CC containing proteins (By similarity).
CC -!- DOMAIN: The major and minor NLS binding sites are mainly involved
CC in recognition of simple or bipartite NLS motifs. Structurally
CC located within in a helical surface groove they contain several
CC conserved Trp and Asn residues of the corresponding third helices
CC (H3) of ARM repeats which mainly contribute to binding (By
CC similarity).
CC -!- MASS SPECTROMETRY: Mass=57861.92; Method=MALDI; Range=1-529;
CC Source=PubMed:11840567;
CC -!- SIMILARITY: Belongs to the importin alpha family.
CC -!- SIMILARITY: Contains 10 ARM repeats.
CC -!- SIMILARITY: Contains 1 IBB domain.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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; BC146905; AAI46906.1; -; mRNA.
DR EMBL; U09559; AAA65700.1; -; mRNA.
DR PIR; A56516; A56516.
DR RefSeq; NP_002257.1; NM_002266.2.
DR RefSeq; XP_005257399.1; XM_005257342.1.
DR RefSeq; XP_005277833.1; XM_005277776.1.
DR UniGene; Hs.594238; -.
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; 4E4V; X-ray; 2.53 A; A/B=70-529.
DR PDBsum; 1EFX; -.
DR PDBsum; 1QGK; -.
DR PDBsum; 1QGR; -.
DR PDBsum; 3FEX; -.
DR PDBsum; 3FEY; -.
DR PDBsum; 4E4V; -.
DR ProteinModelPortal; P52292; -.
DR SMR; P52292; 11-499.
DR DIP; DIP-6205N; -.
DR IntAct; P52292; 73.
DR MINT; MINT-94121; -.
DR STRING; 9606.ENSP00000332455; -.
DR BindingDB; P52292; -.
DR ChEMBL; CHEMBL1741187; -.
DR PhosphoSite; P52292; -.
DR DMDM; 1708480; -.
DR SWISS-2DPAGE; P52292; -.
DR PaxDb; P52292; -.
DR PeptideAtlas; P52292; -.
DR PRIDE; P52292; -.
DR DNASU; 3838; -.
DR Ensembl; ENST00000330459; ENSP00000332455; ENSG00000182481.
DR Ensembl; ENST00000537025; ENSP00000438483; ENSG00000182481.
DR Ensembl; ENST00000571293; ENSP00000460119; ENSG00000262472.
DR Ensembl; ENST00000574083; ENSP00000460025; ENSG00000262472.
DR GeneID; 3838; -.
DR KEGG; hsa:3838; -.
DR UCSC; uc002jgk.3; human.
DR CTD; 3838; -.
DR GeneCards; GC17P066031; -.
DR HGNC; HGNC:6395; KPNA2.
DR HPA; CAB015460; -.
DR MIM; 600685; gene.
DR neXtProt; NX_P52292; -.
DR PharmGKB; PA30186; -.
DR eggNOG; COG5064; -.
DR HOGENOM; HOG000167616; -.
DR HOVERGEN; HBG001846; -.
DR InParanoid; P52292; -.
DR KO; K15043; -.
DR OMA; NETEKLC; -.
DR PhylomeDB; P52292; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P52292; -.
DR ChiTaRS; KPNA2; human.
DR EvolutionaryTrace; P52292; -.
DR GeneWiki; Karyopherin_alpha_2; -.
DR GenomeRNAi; 3838; -.
DR NextBio; 15087; -.
DR PRO; PR:P52292; -.
DR ArrayExpress; P52292; -.
DR Bgee; P52292; -.
DR CleanEx; HS_KPNA2; -.
DR Genevestigator; P52292; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0008139; F:nuclear localization sequence binding; IDA:UniProtKB.
DR GO; GO:0008565; F:protein transporter activity; IEA:InterPro.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0006259; P:DNA metabolic process; TAS:ProtInc.
DR GO; GO:0000085; P:mitotic G2 phase; TAS:ProtInc.
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; IDA:UniProtKB.
DR GO; GO:0000018; P:regulation of DNA recombination; TAS:ProtInc.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR002652; Importin-a_IBB.
DR InterPro; IPR024931; Importing_su_alpha.
DR Pfam; PF00514; Arm; 8.
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; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Host-virus interaction; Nucleus;
KW Phosphoprotein; Polymorphism; Protein transport; Reference proteome;
KW Repeat; Transport.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 529 Importin subunit alpha-1.
FT /FTId=PRO_0000120722.
FT DOMAIN 2 60 IBB.
FT REPEAT 71 111 ARM 1; truncated.
FT REPEAT 112 151 ARM 2.
FT REPEAT 152 193 ARM 3.
FT REPEAT 200 244 ARM 4.
FT REPEAT 246 282 ARM 5.
FT REPEAT 283 322 ARM 6.
FT REPEAT 325 364 ARM 7.
FT REPEAT 367 409 ARM 8.
FT REPEAT 410 456 ARM 9.
FT REPEAT 457 496 ARM 10; atypical.
FT REGION 142 238 NLS binding site (major) (By similarity).
FT REGION 315 403 NLS binding site (minor) (By similarity).
FT MOTIF 45 54 Nuclear localization signal (By
FT similarity).
FT COMPBIAS 28 31 Poly-Arg.
FT COMPBIAS 499 502 Poly-Glu.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 62 62 Phosphoserine.
FT MOD_RES 490 490 Phosphoserine.
FT VARIANT 157 157 A -> V (in dbSNP:rs17850032).
FT /FTId=VAR_067625.
FT VARIANT 165 165 P -> R (in dbSNP:rs11545989).
FT /FTId=VAR_013137.
FT VARIANT 365 365 G -> S (in dbSNP:rs1059558).
FT /FTId=VAR_067626.
FT VARIANT 430 430 T -> P (in dbSNP:rs1059538).
FT /FTId=VAR_014453.
FT VARIANT 453 453 K -> N (in dbSNP:rs17850031).
FT /FTId=VAR_067627.
FT HELIX 14 16
FT TURN 18 21
FT HELIX 30 48
FT HELIX 78 85
FT HELIX 90 104
FT STRAND 106 108
FT HELIX 112 117
FT HELIX 120 129
FT HELIX 134 147
FT HELIX 152 160
FT HELIX 163 170
FT HELIX 176 190
FT HELIX 194 202
FT HELIX 206 211
FT HELIX 218 220
FT HELIX 223 236
FT HELIX 246 259
FT HELIX 265 279
FT HELIX 283 291
FT HELIX 295 301
FT HELIX 307 320
FT HELIX 325 333
FT HELIX 336 344
FT HELIX 349 362
FT HELIX 367 375
FT HELIX 379 388
FT HELIX 391 407
FT HELIX 410 418
FT HELIX 422 427
FT HELIX 428 430
FT HELIX 434 453
FT HELIX 457 466
FT HELIX 469 475
FT HELIX 476 478
FT HELIX 482 495
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
//
MIM
600685
*RECORD*
*FIELD* NO
600685
*FIELD* TI
*600685 KARYOPHERIN ALPHA-2; KPNA2
;;RECOMBINATION-ACTIVATING GENE COHORT 1; RCH1;;
read moreSRP1-ALPHA;;
IMPORTIN ALPHA-1;;
QIP2
*FIELD* TX
CLONING
The import of proteins into the nucleus is a process that involves at
least 2 steps. The first is an energy-independent docking of the protein
to the nuclear envelope and the second is an energy-dependent
translocation through the nuclear pore complex. Imported proteins
require a nuclear localization sequence (NLS) which generally consists
of a short region of basic amino acids or 2 such regions spaced about 10
amino acids apart. Proteins involved in the first step of nuclear import
have been identified in different systems. These include the Xenopus
protein importin and its yeast homolog, SRP1 (a suppressor of certain
temperature-sensitive mutations of RNA polymerase I in Saccharomyces
cerevisiae; see 600686), which bind to the NLS. To find proteins that
interact with the recombination-activating protein RAG1 (179615), Cuomo
et al. (1994) used a 2-hybrid assay and cloned a cDNA, which they
referred to as Rch1 for 'Rag cohort-1' and which was later shown to be
SRP1-alpha. They found that Rch1, along with RAG2 (179616), induced
V(D)J recombinase activity in a variety of nonlymphoid cell types.
The SRP1-like proteins share large blocks of evolutionarily conserved
sequence and belong to a multigene family, the members of which may be
involved in the nuclear transport of a variety of proteins. Using a
yeast 2-hybrid system with a known nuclear protein as bait, Weis et al.
(1995) captured a cDNA from HeLa cells which encodes an NLS receptor.
The full-length cDNA encodes a putative 529-amino acid protein and was
termed SRP1-alpha based on its high homology to the yeast SRP1 gene.
Human SRP1-alpha was shown to bind to the NLS and to mediate the docking
step. When both SRP1-alpha and Ran (601179), another protein implicated
in the transport mechanism, were used in an in vitro assay system, Weis
et al. (1995) were able to reconstitute the nuclear transport machinery
in vitro. This gene is also symbolized KPNA2 for karyopherin alpha-2.
GENE FUNCTION
Epstein-Barr virus (EBV) is implicated in the induction of several
malignancies. Fischer et al. (1997) used a yeast 2-hybrid system to show
that karyopherin alpha-2 forms a complex with the EBV nuclear antigen-1
(EBNA1). Nuclear transport of EBNA1 was impaired by expression of
N-terminally truncated KPNA2.
Seki et al. (1997) demonstrated that KPNA2, which they called QIP2,
interacted with the NLSs of DNA helicase Q1 (RECQL; 600537) and SV40 T
antigen. QIP2 contains 'armadillo' repeats, which are 42-amino acid
motifs implicated in protein-protein interactions. The human QIP2
protein is 63%, 50%, 45%, and 44% identical to the Xenopus
importin-alpha, human QIP1 (602970), S. cerevisiae SRP1, and human KPNA1
(600686) proteins, respectively.
Using an in vitro import assay based on permeabilized HeLa cells to
study the import substrate specificity of all ubiquitously expressed
importins, including KPNA2, Kohler et al. (1999) found that all
importins tested were able to transport HNRNPK (600712) and PCAF
(602303), in addition to the standard test substrates, but only KPNA4
(601892) showed a strong preference for the import of GDP/GTP exchange
factor RCC1 (179710), which is exclusively located inside the nucleus.
When HNRNPK, PCAF, and RCC1 were offered with a competing substrate
nucleoplasmin (164040), they found that substrate binding was diminished
or abolished in some importins and retained in others.
GENE STRUCTURE
Dorr et al. (2001) presented the genomic organization of the KPNA2 gene
with 11 exons spanning approximately 10 kb.
MAPPING
Dorr et al. (2001) localized KPNA2 in close proximity to a translocation
breakpoint on chromosome 17q23-q24.
MOLECULAR GENETICS
KPNA2 is considered a positional candidate gene for Russell-Silver
syndrome (RSS; 180860) (Dorr et al., 2001). However, in a genomic screen
for mutations within all exons and adjacent intronic sequences of KPNA2
from 31 unrelated RSS patients, Dorr et al. (2001) identified several
single-nucleotide polymorphisms (SNPs) but no disease-related mutation.
BIOCHEMICAL FEATURES
- Crystal Structure
Matsuura and Stewart (2004) presented the 2.0-angstrom crystal structure
of the nuclear export complex formed by exportin Cse1p (see 601342)
complexed with its cargo Kap60p (importin-alpha) and RanGTP (see
602362), thereby providing a structural framework for understanding
nuclear protein export and the different functions of RanGTP in export
and import. In the complex, Cse1p coils around both RanGTP and Kap60p,
stabilizing the RanGTP-state and clamping the Kap60p importin-beta (see
602738)-binding domain, ensuring that only cargo-free Kap60p is
exported. By mutagenesis, Matsuura and Stewart (2004) showed that
conformational changes in exportins couple cargo binding to high
affinity for RanGTP, generating a spring-loaded molecule to facilitate
disassembly of the export complex following GTP hydrolysis in the
cytoplasm.
*FIELD* RF
1. Cuomo, C. A.; Kirch, S. A.; Gyuris, J.; Brent, R.; Oettinger, M.
A.: Rch1, a protein that specifically interacts with the RAG-1 recombination-activating
protein. Proc. Nat. Acad. Sci. 91: 6156-6160, 1994.
2. Dorr, S.; Midro, A. T.; Farber, C.; Giannakudis, J.; Hansmann,
I.: Construction of a detailed physical and transcript map of the
candidate region for Russell-Silver syndrome on chromosome 17q23-q24. Genomics 71:
174-181, 2001.
3. Dorr, S.; Schlicker, M.; Hansmann, I.: Genomic structure of karyopherin
alpha-2 (KPNA2) within a low-copy repeat on chromosome 17q23-q24 and
mutation analysis in patients with Russell-Silver syndrome. Hum.
Genet. 109: 479-486, 2001.
4. Fischer, N.; Kremmer, E.; Lautscham, G.; Mueller-Lantzsch, N.;
Grasser, F. A.: Epstein-Barr virus nuclear antigen 1 forms a complex
with the nuclear transporter karyopherin alpha-2. J. Biol. Chem. 272:
3999-4005, 1997.
5. Kohler, M.; Speck, C.; Christiansen, M.; Bischoff, F. R.; Prehn,
S.; Haller, H.; Gorlich, D.; Hartmann, E.: Evidence for distinct
substrate specificities of importin alpha family members in nuclear
protein import. Molec. Cell. Biol. 19: 7782-7791, 1999.
6. Matsuura, Y.; Stewart, M.: Structural basis for the assembly of
a nuclear export complex. Nature 432: 872-877, 2004.
7. Seki, T.; Tada, S.; Katada, T.; Enomoto, T.: Cloning of a cDNA
encoding a novel importin-alpha homologue, Qip1: discrimination of
Qip1 and Rch1 from hSrp1 by their ability to interact with DNA helicase
Q1/RecQL. Biochem. Biophys. Res. Commun. 234: 48-53, 1997.
8. Weis, K.; Mattaj, I. W.; Lamond, A. I.: Identification of hSRP1-alpha
as a functional receptor for nuclear localization sequences. Science 268:
1049-1052, 1995.
*FIELD* CN
Patricia A. Hartz - updated: 11/14/2006
Ada Hamosh - updated: 12/29/2004
Victor A. McKusick - updated: 12/6/2001
Patti M. Sherman - updated: 8/17/1998
Mark H. Paalman - updated: 4/7/1997
Alan F. Scott - updated: 11/3/1995
*FIELD* CD
Alan F. Scott: 7/26/1995
*FIELD* ED
carol: 02/03/2009
wwang: 11/14/2006
alopez: 1/3/2005
alopez: 12/30/2004
terry: 12/29/2004
carol: 12/7/2001
terry: 12/6/2001
alopez: 8/25/1998
psherman: 8/17/1998
carol: 8/4/1998
carol: 5/1/1998
mark: 4/7/1997
mark: 4/7/1996
mark: 7/26/1995
*RECORD*
*FIELD* NO
600685
*FIELD* TI
*600685 KARYOPHERIN ALPHA-2; KPNA2
;;RECOMBINATION-ACTIVATING GENE COHORT 1; RCH1;;
read moreSRP1-ALPHA;;
IMPORTIN ALPHA-1;;
QIP2
*FIELD* TX
CLONING
The import of proteins into the nucleus is a process that involves at
least 2 steps. The first is an energy-independent docking of the protein
to the nuclear envelope and the second is an energy-dependent
translocation through the nuclear pore complex. Imported proteins
require a nuclear localization sequence (NLS) which generally consists
of a short region of basic amino acids or 2 such regions spaced about 10
amino acids apart. Proteins involved in the first step of nuclear import
have been identified in different systems. These include the Xenopus
protein importin and its yeast homolog, SRP1 (a suppressor of certain
temperature-sensitive mutations of RNA polymerase I in Saccharomyces
cerevisiae; see 600686), which bind to the NLS. To find proteins that
interact with the recombination-activating protein RAG1 (179615), Cuomo
et al. (1994) used a 2-hybrid assay and cloned a cDNA, which they
referred to as Rch1 for 'Rag cohort-1' and which was later shown to be
SRP1-alpha. They found that Rch1, along with RAG2 (179616), induced
V(D)J recombinase activity in a variety of nonlymphoid cell types.
The SRP1-like proteins share large blocks of evolutionarily conserved
sequence and belong to a multigene family, the members of which may be
involved in the nuclear transport of a variety of proteins. Using a
yeast 2-hybrid system with a known nuclear protein as bait, Weis et al.
(1995) captured a cDNA from HeLa cells which encodes an NLS receptor.
The full-length cDNA encodes a putative 529-amino acid protein and was
termed SRP1-alpha based on its high homology to the yeast SRP1 gene.
Human SRP1-alpha was shown to bind to the NLS and to mediate the docking
step. When both SRP1-alpha and Ran (601179), another protein implicated
in the transport mechanism, were used in an in vitro assay system, Weis
et al. (1995) were able to reconstitute the nuclear transport machinery
in vitro. This gene is also symbolized KPNA2 for karyopherin alpha-2.
GENE FUNCTION
Epstein-Barr virus (EBV) is implicated in the induction of several
malignancies. Fischer et al. (1997) used a yeast 2-hybrid system to show
that karyopherin alpha-2 forms a complex with the EBV nuclear antigen-1
(EBNA1). Nuclear transport of EBNA1 was impaired by expression of
N-terminally truncated KPNA2.
Seki et al. (1997) demonstrated that KPNA2, which they called QIP2,
interacted with the NLSs of DNA helicase Q1 (RECQL; 600537) and SV40 T
antigen. QIP2 contains 'armadillo' repeats, which are 42-amino acid
motifs implicated in protein-protein interactions. The human QIP2
protein is 63%, 50%, 45%, and 44% identical to the Xenopus
importin-alpha, human QIP1 (602970), S. cerevisiae SRP1, and human KPNA1
(600686) proteins, respectively.
Using an in vitro import assay based on permeabilized HeLa cells to
study the import substrate specificity of all ubiquitously expressed
importins, including KPNA2, Kohler et al. (1999) found that all
importins tested were able to transport HNRNPK (600712) and PCAF
(602303), in addition to the standard test substrates, but only KPNA4
(601892) showed a strong preference for the import of GDP/GTP exchange
factor RCC1 (179710), which is exclusively located inside the nucleus.
When HNRNPK, PCAF, and RCC1 were offered with a competing substrate
nucleoplasmin (164040), they found that substrate binding was diminished
or abolished in some importins and retained in others.
GENE STRUCTURE
Dorr et al. (2001) presented the genomic organization of the KPNA2 gene
with 11 exons spanning approximately 10 kb.
MAPPING
Dorr et al. (2001) localized KPNA2 in close proximity to a translocation
breakpoint on chromosome 17q23-q24.
MOLECULAR GENETICS
KPNA2 is considered a positional candidate gene for Russell-Silver
syndrome (RSS; 180860) (Dorr et al., 2001). However, in a genomic screen
for mutations within all exons and adjacent intronic sequences of KPNA2
from 31 unrelated RSS patients, Dorr et al. (2001) identified several
single-nucleotide polymorphisms (SNPs) but no disease-related mutation.
BIOCHEMICAL FEATURES
- Crystal Structure
Matsuura and Stewart (2004) presented the 2.0-angstrom crystal structure
of the nuclear export complex formed by exportin Cse1p (see 601342)
complexed with its cargo Kap60p (importin-alpha) and RanGTP (see
602362), thereby providing a structural framework for understanding
nuclear protein export and the different functions of RanGTP in export
and import. In the complex, Cse1p coils around both RanGTP and Kap60p,
stabilizing the RanGTP-state and clamping the Kap60p importin-beta (see
602738)-binding domain, ensuring that only cargo-free Kap60p is
exported. By mutagenesis, Matsuura and Stewart (2004) showed that
conformational changes in exportins couple cargo binding to high
affinity for RanGTP, generating a spring-loaded molecule to facilitate
disassembly of the export complex following GTP hydrolysis in the
cytoplasm.
*FIELD* RF
1. Cuomo, C. A.; Kirch, S. A.; Gyuris, J.; Brent, R.; Oettinger, M.
A.: Rch1, a protein that specifically interacts with the RAG-1 recombination-activating
protein. Proc. Nat. Acad. Sci. 91: 6156-6160, 1994.
2. Dorr, S.; Midro, A. T.; Farber, C.; Giannakudis, J.; Hansmann,
I.: Construction of a detailed physical and transcript map of the
candidate region for Russell-Silver syndrome on chromosome 17q23-q24. Genomics 71:
174-181, 2001.
3. Dorr, S.; Schlicker, M.; Hansmann, I.: Genomic structure of karyopherin
alpha-2 (KPNA2) within a low-copy repeat on chromosome 17q23-q24 and
mutation analysis in patients with Russell-Silver syndrome. Hum.
Genet. 109: 479-486, 2001.
4. Fischer, N.; Kremmer, E.; Lautscham, G.; Mueller-Lantzsch, N.;
Grasser, F. A.: Epstein-Barr virus nuclear antigen 1 forms a complex
with the nuclear transporter karyopherin alpha-2. J. Biol. Chem. 272:
3999-4005, 1997.
5. Kohler, M.; Speck, C.; Christiansen, M.; Bischoff, F. R.; Prehn,
S.; Haller, H.; Gorlich, D.; Hartmann, E.: Evidence for distinct
substrate specificities of importin alpha family members in nuclear
protein import. Molec. Cell. Biol. 19: 7782-7791, 1999.
6. Matsuura, Y.; Stewart, M.: Structural basis for the assembly of
a nuclear export complex. Nature 432: 872-877, 2004.
7. Seki, T.; Tada, S.; Katada, T.; Enomoto, T.: Cloning of a cDNA
encoding a novel importin-alpha homologue, Qip1: discrimination of
Qip1 and Rch1 from hSrp1 by their ability to interact with DNA helicase
Q1/RecQL. Biochem. Biophys. Res. Commun. 234: 48-53, 1997.
8. Weis, K.; Mattaj, I. W.; Lamond, A. I.: Identification of hSRP1-alpha
as a functional receptor for nuclear localization sequences. Science 268:
1049-1052, 1995.
*FIELD* CN
Patricia A. Hartz - updated: 11/14/2006
Ada Hamosh - updated: 12/29/2004
Victor A. McKusick - updated: 12/6/2001
Patti M. Sherman - updated: 8/17/1998
Mark H. Paalman - updated: 4/7/1997
Alan F. Scott - updated: 11/3/1995
*FIELD* CD
Alan F. Scott: 7/26/1995
*FIELD* ED
carol: 02/03/2009
wwang: 11/14/2006
alopez: 1/3/2005
alopez: 12/30/2004
terry: 12/29/2004
carol: 12/7/2001
terry: 12/6/2001
alopez: 8/25/1998
psherman: 8/17/1998
carol: 8/4/1998
carol: 5/1/1998
mark: 4/7/1997
mark: 4/7/1996
mark: 7/26/1995