Full text data of KPNA1
KPNA1
(RCH2)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Importin subunit alpha-5 (Karyopherin subunit alpha-1; Nucleoprotein interactor 1; NPI-1; RAG cohort protein 2; SRP1-beta; Importin subunit alpha-5, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Importin subunit alpha-5 (Karyopherin subunit alpha-1; Nucleoprotein interactor 1; NPI-1; RAG cohort protein 2; SRP1-beta; Importin subunit alpha-5, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P52294
ID IMA5_HUMAN Reviewed; 538 AA.
AC P52294; D3DN93; Q6IBQ9; Q9BQ56;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 18-MAY-2010, sequence version 3.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=Importin subunit alpha-5;
DE AltName: Full=Karyopherin subunit alpha-1;
DE AltName: Full=Nucleoprotein interactor 1;
DE Short=NPI-1;
DE AltName: Full=RAG cohort protein 2;
DE AltName: Full=SRP1-beta;
DE Contains:
DE RecName: Full=Importin subunit alpha-5, N-terminally processed;
GN Name=KPNA1; Synonyms=RCH2;
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=7831767; DOI=10.1016/S0042-6822(95)80026-3;
RA O'Neill R.E., Palese P.;
RT "NPI-1, the human homolog of SRP-1, interacts with influenza virus
RT nucleoprotein.";
RL Virology 206:116-125(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-73.
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 (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-73.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASN-73.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-73.
RC TISSUE=Lung;
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 [7]
RP INTERACTION WITH RAG1.
RX PubMed=8052633; DOI=10.1073/pnas.91.16.7633;
RA Cortes P., Ye Z.-S., Baltimore D.;
RT "RAG-1 interacts with the repeated amino acid motif of the human
RT homologue of the yeast protein SRP1.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:7633-7637(1994).
RN [8]
RP CHARACTERIZATION.
RX PubMed=7892216; DOI=10.1073/pnas.92.6.2008;
RA Moroianu J., Blobel G., Radu A.;
RT "Previously identified protein of uncertain function is karyopherin
RT alpha and together with karyopherin beta docks import substrate at
RT nuclear pore complexes.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:2008-2011(1995).
RN [9]
RP PROTEIN SEQUENCE OF 481-495, AND DOMAINS IBB.
RX PubMed=8692858; DOI=10.1073/pnas.93.13.6572;
RA Moroianu J., Blobel G., Radu A.;
RT "The binding site of karyopherin alpha for karyopherin beta overlaps
RT with a nuclear localization sequence.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:6572-6576(1996).
RN [10]
RP SUBCELLULAR LOCATION, AND SUBUNIT.
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 [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 HCMV UL84.
RX PubMed=12610148; DOI=10.1128/JVI.77.6.3734-3748.2003;
RA Lischka P., Sorg G., Kann M., Winkler M., Stamminger T.;
RT "A nonconventional nuclear localization signal within the UL84 protein
RT of human cytomegalovirus mediates nuclear import via the importin
RT alpha/beta pathway.";
RL J. Virol. 77:3734-3748(2003).
RN [13]
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 [14]
RP INTERACTION WITH EBOLAVIRUS VP24.
RX PubMed=16698996; DOI=10.1128/JVI.02349-05;
RA Reid S.P., Leung L.W., Hartman A.L., Martinez O., Shaw M.L.,
RA Carbonnelle C., Volchkov V.E., Nichol S.T., Basler C.F.;
RT "Ebola virus VP24 binds karyopherin alpha-1 and blocks STAT1 nuclear
RT accumulation.";
RL J. Virol. 80:5156-5167(2006).
RN [15]
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 [16]
RP UBIQUITINATION.
RX PubMed=19118899; DOI=10.1016/j.molimm.2008.11.009;
RA Simkus C., Makiya M., Jones J.M.;
RT "Karyopherin alpha 1 is a putative substrate of the RAG1 ubiquitin
RT ligase.";
RL Mol. Immunol. 46:1319-1325(2009).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
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 [18]
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 [19]
RP INTERACTION WITH CTNNBL1 AND AICDA.
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 [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND THR-2, MASS
RP SPECTROMETRY, AND CLEAVAGE OF INITIATOR METHIONINE.
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).
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. In vitro, mediates the nuclear
CC import of human cytomegalovirus UL84 by recognizing a non-
CC classical NLS.
CC -!- SUBUNIT: Heterodimer; with KPNB1. Interacts with ANP32E. Interacts
CC with ZIC3 (By similarity). Interacts with NSMF; the interaction
CC occurs in a calcium-independent manner after synaptic NMDA
CC receptor stimulation and is required for nuclear import of NSMF
CC but is competed by CABP1 (By similarity). Interacts with the
CC nucleoprotein of influenza A viruses. Binds to HCMV (human
CC cytomegalovirus) UL84, HIV-1 Vpr and to ebolavirus VP24. Interacts
CC with APEX1 and RAG1. Interacts with CTNNBL1 (via its N-terminal).
CC Interacts with AICDA (via its NLS). Interacts with SNAI1 (via zinc
CC fingers).
CC -!- INTERACTION:
CC Q5TAQ9:DCAF8; NbExp=2; IntAct=EBI-358383, EBI-740686;
CC Q13255:GRM1; NbExp=2; IntAct=EBI-358383, EBI-8527352;
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 -!- PTM: Polyubiquitinated in the presence of RAG1 (in vitro).
CC -!- SIMILARITY: Belongs to the importin alpha family.
CC -!- SIMILARITY: Contains 10 ARM repeats.
CC -!- SIMILARITY: Contains 1 IBB domain.
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DR EMBL; S75295; AAC60648.1; -; mRNA.
DR EMBL; BT006959; AAP35605.1; -; mRNA.
DR EMBL; CR456743; CAG33024.1; -; mRNA.
DR EMBL; AC083798; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC096861; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW79482.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79483.1; -; Genomic_DNA.
DR EMBL; BC002374; AAH02374.1; -; mRNA.
DR EMBL; BC003009; AAH03009.1; -; mRNA.
DR PIR; I59931; I59931.
DR RefSeq; NP_002255.3; NM_002264.3.
DR RefSeq; XP_005247494.1; XM_005247437.1.
DR UniGene; Hs.161008; -.
DR PDB; 2JDQ; X-ray; 2.20 A; A/B=66-512.
DR PDB; 3TJ3; X-ray; 2.70 A; A/B=66-512.
DR PDB; 4B18; X-ray; 2.52 A; A=66-512.
DR PDBsum; 2JDQ; -.
DR PDBsum; 3TJ3; -.
DR PDBsum; 4B18; -.
DR ProteinModelPortal; P52294; -.
DR SMR; P52294; 10-509.
DR DIP; DIP-29296N; -.
DR IntAct; P52294; 33.
DR MINT; MINT-240027; -.
DR STRING; 9606.ENSP00000343701; -.
DR PhosphoSite; P52294; -.
DR DMDM; 296439328; -.
DR PaxDb; P52294; -.
DR PRIDE; P52294; -.
DR DNASU; 3836; -.
DR Ensembl; ENST00000344337; ENSP00000343701; ENSG00000114030.
DR GeneID; 3836; -.
DR KEGG; hsa:3836; -.
DR UCSC; uc003efb.1; human.
DR CTD; 3836; -.
DR GeneCards; GC03M122140; -.
DR HGNC; HGNC:6394; KPNA1.
DR HPA; HPA053627; -.
DR MIM; 600686; gene.
DR neXtProt; NX_P52294; -.
DR PharmGKB; PA30185; -.
DR eggNOG; COG5064; -.
DR HOGENOM; HOG000167616; -.
DR HOVERGEN; HBG001846; -.
DR InParanoid; P52294; -.
DR KO; K15042; -.
DR OMA; VIDAHIF; -.
DR OrthoDB; EOG7VHSWV; -.
DR PhylomeDB; P52294; -.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P52294; -.
DR EvolutionaryTrace; P52294; -.
DR GeneWiki; Karyopherin_alpha_1; -.
DR GenomeRNAi; 3836; -.
DR NextBio; 15079; -.
DR PMAP-CutDB; P52294; -.
DR PRO; PR:P52294; -.
DR ArrayExpress; P52294; -.
DR Bgee; P52294; -.
DR CleanEx; HS_KPNA1; -.
DR Genevestigator; P52294; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
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:InterPro.
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:0042307; P:positive regulation of protein import into nucleus; ISS: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; 4.
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 Polymorphism; Protein transport; Reference proteome; Repeat;
KW Transport; Ubl conjugation.
FT CHAIN 1 538 Importin subunit alpha-5.
FT /FTId=PRO_0000120719.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 538 Importin subunit alpha-5, N-terminally
FT processed.
FT /FTId=PRO_0000424491.
FT DOMAIN 1 57 IBB.
FT REPEAT 77 117 ARM 1; truncated.
FT REPEAT 118 161 ARM 2.
FT REPEAT 162 206 ARM 3.
FT REPEAT 207 245 ARM 4.
FT REPEAT 246 290 ARM 5.
FT REPEAT 291 330 ARM 6.
FT REPEAT 331 372 ARM 7.
FT REPEAT 373 412 ARM 8.
FT REPEAT 413 457 ARM 9.
FT REPEAT 460 504 ARM 10; atypical.
FT REGION 149 241 NLS binding site (major) (By similarity).
FT REGION 245 437 Binding to RAG1.
FT REGION 318 406 NLS binding site (minor) (By similarity).
FT MOTIF 42 51 Nuclear localization signal (By
FT similarity).
FT COMPBIAS 25 28 Poly-Arg.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylthreonine; in Importin subunit
FT alpha-5, N-terminally processed.
FT VARIANT 73 73 S -> N (in dbSNP:rs4678193).
FT /FTId=VAR_050002.
FT CONFLICT 142 142 T -> S (in Ref. 1; AAC60648).
FT CONFLICT 169 169 G -> R (in Ref. 1; AAC60648).
FT HELIX 85 92
FT HELIX 96 111
FT STRAND 112 115
FT HELIX 118 122
FT HELIX 127 135
FT HELIX 141 155
FT HELIX 159 167
FT HELIX 170 177
FT HELIX 183 197
FT HELIX 201 209
FT HELIX 213 219
FT HELIX 226 240
FT STRAND 243 245
FT HELIX 249 251
FT HELIX 253 255
FT HELIX 256 262
FT HELIX 268 281
FT STRAND 283 285
FT HELIX 286 294
FT TURN 295 297
FT HELIX 298 304
FT HELIX 310 323
FT HELIX 328 335
FT TURN 336 338
FT HELIX 339 346
FT HELIX 352 365
FT HELIX 370 378
FT HELIX 381 391
FT HELIX 394 410
FT HELIX 413 422
FT HELIX 425 430
FT HELIX 431 433
FT HELIX 437 460
FT STRAND 461 463
FT HELIX 468 476
FT HELIX 478 485
FT HELIX 487 504
SQ SEQUENCE 538 AA; 60222 MW; E8407A3352D6051C CRC64;
MTTPGKENFR LKSYKNKSLN PDEMRRRREE EGLQLRKQKR EEQLFKRRNV ATAEEETEEE
VMSDGGFHEA QISNMEMAPG GVITSDMIEM IFSKSPEQQL SATQKFRKLL SKEPNPPIDE
VISTPGVVAR FVEFLKRKEN CTLQFESAWV LTNIASGNSL QTRIVIQAGA VPIFIELLSS
EFEDVQEQAV WALGNIAGDS TMCRDYVLDC NILPPLLQLF SKQNRLTMTR NAVWALSNLC
RGKSPPPEFA KVSPCLNVLS WLLFVSDTDV LADACWALSY LSDGPNDKIQ AVIDAGVCRR
LVELLMHNDY KVVSPALRAV GNIVTGDDIQ TQVILNCSAL QSLLHLLSSP KESIKKEACW
TISNITAGNR AQIQTVIDAN IFPALISILQ TAEFRTRKEA AWAITNATSG GSAEQIKYLV
ELGCIKPLCD LLTVMDSKIV QVALNGLENI LRLGEQEAKR NGTGINPYCA LIEEAYGLDK
IEFLQSHENQ EIYQKAFDLI EHYFGTEDED SSIAPQVDLN QQQYIFQQCE APMEGFQL
//
ID IMA5_HUMAN Reviewed; 538 AA.
AC P52294; D3DN93; Q6IBQ9; Q9BQ56;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 18-MAY-2010, sequence version 3.
DT 22-JAN-2014, entry version 148.
DE RecName: Full=Importin subunit alpha-5;
DE AltName: Full=Karyopherin subunit alpha-1;
DE AltName: Full=Nucleoprotein interactor 1;
DE Short=NPI-1;
DE AltName: Full=RAG cohort protein 2;
DE AltName: Full=SRP1-beta;
DE Contains:
DE RecName: Full=Importin subunit alpha-5, N-terminally processed;
GN Name=KPNA1; Synonyms=RCH2;
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=7831767; DOI=10.1016/S0042-6822(95)80026-3;
RA O'Neill R.E., Palese P.;
RT "NPI-1, the human homolog of SRP-1, interacts with influenza virus
RT nucleoprotein.";
RL Virology 206:116-125(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-73.
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 (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-73.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASN-73.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-73.
RC TISSUE=Lung;
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 [7]
RP INTERACTION WITH RAG1.
RX PubMed=8052633; DOI=10.1073/pnas.91.16.7633;
RA Cortes P., Ye Z.-S., Baltimore D.;
RT "RAG-1 interacts with the repeated amino acid motif of the human
RT homologue of the yeast protein SRP1.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:7633-7637(1994).
RN [8]
RP CHARACTERIZATION.
RX PubMed=7892216; DOI=10.1073/pnas.92.6.2008;
RA Moroianu J., Blobel G., Radu A.;
RT "Previously identified protein of uncertain function is karyopherin
RT alpha and together with karyopherin beta docks import substrate at
RT nuclear pore complexes.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:2008-2011(1995).
RN [9]
RP PROTEIN SEQUENCE OF 481-495, AND DOMAINS IBB.
RX PubMed=8692858; DOI=10.1073/pnas.93.13.6572;
RA Moroianu J., Blobel G., Radu A.;
RT "The binding site of karyopherin alpha for karyopherin beta overlaps
RT with a nuclear localization sequence.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:6572-6576(1996).
RN [10]
RP SUBCELLULAR LOCATION, AND SUBUNIT.
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 [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 HCMV UL84.
RX PubMed=12610148; DOI=10.1128/JVI.77.6.3734-3748.2003;
RA Lischka P., Sorg G., Kann M., Winkler M., Stamminger T.;
RT "A nonconventional nuclear localization signal within the UL84 protein
RT of human cytomegalovirus mediates nuclear import via the importin
RT alpha/beta pathway.";
RL J. Virol. 77:3734-3748(2003).
RN [13]
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 [14]
RP INTERACTION WITH EBOLAVIRUS VP24.
RX PubMed=16698996; DOI=10.1128/JVI.02349-05;
RA Reid S.P., Leung L.W., Hartman A.L., Martinez O., Shaw M.L.,
RA Carbonnelle C., Volchkov V.E., Nichol S.T., Basler C.F.;
RT "Ebola virus VP24 binds karyopherin alpha-1 and blocks STAT1 nuclear
RT accumulation.";
RL J. Virol. 80:5156-5167(2006).
RN [15]
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 [16]
RP UBIQUITINATION.
RX PubMed=19118899; DOI=10.1016/j.molimm.2008.11.009;
RA Simkus C., Makiya M., Jones J.M.;
RT "Karyopherin alpha 1 is a putative substrate of the RAG1 ubiquitin
RT ligase.";
RL Mol. Immunol. 46:1319-1325(2009).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
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 [18]
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 [19]
RP INTERACTION WITH CTNNBL1 AND AICDA.
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 [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND THR-2, MASS
RP SPECTROMETRY, AND CLEAVAGE OF INITIATOR METHIONINE.
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).
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. In vitro, mediates the nuclear
CC import of human cytomegalovirus UL84 by recognizing a non-
CC classical NLS.
CC -!- SUBUNIT: Heterodimer; with KPNB1. Interacts with ANP32E. Interacts
CC with ZIC3 (By similarity). Interacts with NSMF; the interaction
CC occurs in a calcium-independent manner after synaptic NMDA
CC receptor stimulation and is required for nuclear import of NSMF
CC but is competed by CABP1 (By similarity). Interacts with the
CC nucleoprotein of influenza A viruses. Binds to HCMV (human
CC cytomegalovirus) UL84, HIV-1 Vpr and to ebolavirus VP24. Interacts
CC with APEX1 and RAG1. Interacts with CTNNBL1 (via its N-terminal).
CC Interacts with AICDA (via its NLS). Interacts with SNAI1 (via zinc
CC fingers).
CC -!- INTERACTION:
CC Q5TAQ9:DCAF8; NbExp=2; IntAct=EBI-358383, EBI-740686;
CC Q13255:GRM1; NbExp=2; IntAct=EBI-358383, EBI-8527352;
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 -!- PTM: Polyubiquitinated in the presence of RAG1 (in vitro).
CC -!- SIMILARITY: Belongs to the importin alpha family.
CC -!- SIMILARITY: Contains 10 ARM repeats.
CC -!- SIMILARITY: Contains 1 IBB domain.
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DR EMBL; S75295; AAC60648.1; -; mRNA.
DR EMBL; BT006959; AAP35605.1; -; mRNA.
DR EMBL; CR456743; CAG33024.1; -; mRNA.
DR EMBL; AC083798; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC096861; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW79482.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79483.1; -; Genomic_DNA.
DR EMBL; BC002374; AAH02374.1; -; mRNA.
DR EMBL; BC003009; AAH03009.1; -; mRNA.
DR PIR; I59931; I59931.
DR RefSeq; NP_002255.3; NM_002264.3.
DR RefSeq; XP_005247494.1; XM_005247437.1.
DR UniGene; Hs.161008; -.
DR PDB; 2JDQ; X-ray; 2.20 A; A/B=66-512.
DR PDB; 3TJ3; X-ray; 2.70 A; A/B=66-512.
DR PDB; 4B18; X-ray; 2.52 A; A=66-512.
DR PDBsum; 2JDQ; -.
DR PDBsum; 3TJ3; -.
DR PDBsum; 4B18; -.
DR ProteinModelPortal; P52294; -.
DR SMR; P52294; 10-509.
DR DIP; DIP-29296N; -.
DR IntAct; P52294; 33.
DR MINT; MINT-240027; -.
DR STRING; 9606.ENSP00000343701; -.
DR PhosphoSite; P52294; -.
DR DMDM; 296439328; -.
DR PaxDb; P52294; -.
DR PRIDE; P52294; -.
DR DNASU; 3836; -.
DR Ensembl; ENST00000344337; ENSP00000343701; ENSG00000114030.
DR GeneID; 3836; -.
DR KEGG; hsa:3836; -.
DR UCSC; uc003efb.1; human.
DR CTD; 3836; -.
DR GeneCards; GC03M122140; -.
DR HGNC; HGNC:6394; KPNA1.
DR HPA; HPA053627; -.
DR MIM; 600686; gene.
DR neXtProt; NX_P52294; -.
DR PharmGKB; PA30185; -.
DR eggNOG; COG5064; -.
DR HOGENOM; HOG000167616; -.
DR HOVERGEN; HBG001846; -.
DR InParanoid; P52294; -.
DR KO; K15042; -.
DR OMA; VIDAHIF; -.
DR OrthoDB; EOG7VHSWV; -.
DR PhylomeDB; P52294; -.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P52294; -.
DR EvolutionaryTrace; P52294; -.
DR GeneWiki; Karyopherin_alpha_1; -.
DR GenomeRNAi; 3836; -.
DR NextBio; 15079; -.
DR PMAP-CutDB; P52294; -.
DR PRO; PR:P52294; -.
DR ArrayExpress; P52294; -.
DR Bgee; P52294; -.
DR CleanEx; HS_KPNA1; -.
DR Genevestigator; P52294; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
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:InterPro.
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:0042307; P:positive regulation of protein import into nucleus; ISS: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; 4.
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 Polymorphism; Protein transport; Reference proteome; Repeat;
KW Transport; Ubl conjugation.
FT CHAIN 1 538 Importin subunit alpha-5.
FT /FTId=PRO_0000120719.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 538 Importin subunit alpha-5, N-terminally
FT processed.
FT /FTId=PRO_0000424491.
FT DOMAIN 1 57 IBB.
FT REPEAT 77 117 ARM 1; truncated.
FT REPEAT 118 161 ARM 2.
FT REPEAT 162 206 ARM 3.
FT REPEAT 207 245 ARM 4.
FT REPEAT 246 290 ARM 5.
FT REPEAT 291 330 ARM 6.
FT REPEAT 331 372 ARM 7.
FT REPEAT 373 412 ARM 8.
FT REPEAT 413 457 ARM 9.
FT REPEAT 460 504 ARM 10; atypical.
FT REGION 149 241 NLS binding site (major) (By similarity).
FT REGION 245 437 Binding to RAG1.
FT REGION 318 406 NLS binding site (minor) (By similarity).
FT MOTIF 42 51 Nuclear localization signal (By
FT similarity).
FT COMPBIAS 25 28 Poly-Arg.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylthreonine; in Importin subunit
FT alpha-5, N-terminally processed.
FT VARIANT 73 73 S -> N (in dbSNP:rs4678193).
FT /FTId=VAR_050002.
FT CONFLICT 142 142 T -> S (in Ref. 1; AAC60648).
FT CONFLICT 169 169 G -> R (in Ref. 1; AAC60648).
FT HELIX 85 92
FT HELIX 96 111
FT STRAND 112 115
FT HELIX 118 122
FT HELIX 127 135
FT HELIX 141 155
FT HELIX 159 167
FT HELIX 170 177
FT HELIX 183 197
FT HELIX 201 209
FT HELIX 213 219
FT HELIX 226 240
FT STRAND 243 245
FT HELIX 249 251
FT HELIX 253 255
FT HELIX 256 262
FT HELIX 268 281
FT STRAND 283 285
FT HELIX 286 294
FT TURN 295 297
FT HELIX 298 304
FT HELIX 310 323
FT HELIX 328 335
FT TURN 336 338
FT HELIX 339 346
FT HELIX 352 365
FT HELIX 370 378
FT HELIX 381 391
FT HELIX 394 410
FT HELIX 413 422
FT HELIX 425 430
FT HELIX 431 433
FT HELIX 437 460
FT STRAND 461 463
FT HELIX 468 476
FT HELIX 478 485
FT HELIX 487 504
SQ SEQUENCE 538 AA; 60222 MW; E8407A3352D6051C CRC64;
MTTPGKENFR LKSYKNKSLN PDEMRRRREE EGLQLRKQKR EEQLFKRRNV ATAEEETEEE
VMSDGGFHEA QISNMEMAPG GVITSDMIEM IFSKSPEQQL SATQKFRKLL SKEPNPPIDE
VISTPGVVAR FVEFLKRKEN CTLQFESAWV LTNIASGNSL QTRIVIQAGA VPIFIELLSS
EFEDVQEQAV WALGNIAGDS TMCRDYVLDC NILPPLLQLF SKQNRLTMTR NAVWALSNLC
RGKSPPPEFA KVSPCLNVLS WLLFVSDTDV LADACWALSY LSDGPNDKIQ AVIDAGVCRR
LVELLMHNDY KVVSPALRAV GNIVTGDDIQ TQVILNCSAL QSLLHLLSSP KESIKKEACW
TISNITAGNR AQIQTVIDAN IFPALISILQ TAEFRTRKEA AWAITNATSG GSAEQIKYLV
ELGCIKPLCD LLTVMDSKIV QVALNGLENI LRLGEQEAKR NGTGINPYCA LIEEAYGLDK
IEFLQSHENQ EIYQKAFDLI EHYFGTEDED SSIAPQVDLN QQQYIFQQCE APMEGFQL
//
MIM
600686
*RECORD*
*FIELD* NO
600686
*FIELD* TI
*600686 KARYOPHERIN ALPHA-1; KPNA1
;;SUPPRESSOR OF RNA POLYMERASE I MUTATION, S. CEREVISIAE, HOMOLOG OF;
read moreSRP1;;
RECOMBINATION ACTIVATING GENE COHORT 2; RCH2;;
IMPORTIN ALPHA-5
*FIELD* TX
CLONING
Cortes et al. (1994) used the 2-hybrid protein interaction systems to
isolate a protein that specifically interacts with RAG1 (179615). The
genes RAG1 and RAG2 (179616) are able to activate V(D)J recombination
when transfected into fibroblasts. Further, knockout mice for these 2
loci lack B and T cells. Several other ubiquitously expressed proteins
are thought to be recruited in the recombination process. Among these
are the genes affected in severe combined immune deficiency (e.g.,
600899) and genes involved in ds-DNA break repair. The human cDNA
identified by Cortes et al. (1994) encodes a 489-amino acid polypeptide
that shows striking similarity to the yeast SRP1 protein, a mutant
allele which can suppress a mutation of RNA polymerase I. The authors
obtained human and mouse cDNA sequences which are 98% identical as
proteins. When RAG1 and human SRP1 were cotransfected into 293T cells a
stable complex of the 2 was observed. The authors speculated that
because SRP1 appears to be bound to the nuclear envelope, the
interaction with RAG1 may serve to localize that protein to the envelope
as well.
GENE FUNCTION
Using an in vitro import assay based on permeabilized HeLa cells to
study the import substrate specificity of all ubiquitously expressed
importins, including KPNA1, 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.
By Western blot analysis and in vitro binding assays, Ma and Cao (2006)
found that nuclear translocation of STAT3 (102582) and STAT1 (600555) is
mediated by binding of human KPNA1 and KPNA6.
King et al. (2006) showed that integral inner nuclear membrane proteins
possess basic sequence motifs that resemble classical nuclear
localization signals. These sequences can mediate direct binding to
karyopherin-alpha and are essential for the passage of integral membrane
proteins to the inner nuclear membrane. Furthermore, karyopherin-alpha,
karyopherin-beta-1 (602738), and the Ran GTPase cycle are required for
inner nuclear membrane targeting, underscoring parallels between
mechanisms governing the targeting of integral inner nuclear membrane
proteins and soluble nuclear transport. King et al. (2006) also provided
evidence that specific nuclear pore complex proteins contribute to this
process, suggesting a role for signal-mediated alterations in the
nuclear pore complex to allow for passage of inner nuclear membrane
proteins along the pore membrane.
MAPPING
By fluorescence in situ hybridization, Ayala-Madrigal et al. (2000)
mapped the human KPNA1 gene to chromosome 3q21.
BIOCHEMICAL FEATURES
Conti et al. (1998) reported the crystal structure of a 50-kD fragment
of the 60-kD yeast karyopherin alpha, in the absence and presence of a
monopartite nuclear localization signal (NLS) peptide at 2.2-angstrom
and 2.8-angstrom resolution, respectively. The structure showed a tandem
array of 10 armadillo repeats, organized in a right-handed superhelix of
helices. Binding of the NLS peptide occurred at 2 sites within a helical
surface groove. The structure reveals the determinants of NLS
specificity and suggested a model for the recognition of bipartite NLSs.
*FIELD* RF
1. Ayala-Madrigal, M. L.; Doerr, S.; Ramirez-Duenas, M. L.; Hansmann,
I.: Assignment of karyopherin alpha 1 (KPNA1) to human chromosome
band 3q21 by in situ hybridization. Cytogenet. Cell Genet. 90: 58-59,
2000.
2. Conti, E.; Uy, M.; Leighton, L.; Blobel, G.; Kuriyan, J.: Crystallographic
analysis of the recognition of a nuclear localization signal by the
nuclear import factor karyopherin alpha. Cell 94: 193-204, 1998.
3. Cortes, P.; Ye, Z.-S.; Baltimore, D.: RAG-1 interacts with the
repeated amino acid motif of the human homologue of the yeast protein
SRP1. Proc. Nat. Acad. Sci. 91: 7633-7637, 1994.
4. King, M. C.; Lusk, C. P.; Blobel, G.: Karyopherin-mediated import
of integral inner nuclear membrane proteins. Nature 442: 1003-1007,
2006.
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. Ma, J.; Cao, X.: Regulation of Stat3 nuclear import by importin
alpha-5 and importin alpha-7 via two different functional sequence
elements. Cell. Signal. 18: 1117-1126, 2006.
*FIELD* CN
Patricia A. Hartz - updated: 11/14/2006
Ada Hamosh - updated: 10/24/2006
Carol A. Bocchini - updated: 2/12/2001
Stylianos E. Antonarakis - updated: 8/3/1998
Alan F. Scott - updated: 11/3/1995
*FIELD* CD
Alan F. Scott: 7/26/1995
*FIELD* ED
wwang: 11/14/2006
alopez: 11/1/2006
terry: 10/24/2006
ckniffin: 10/28/2004
carol: 2/12/2001
terry: 11/13/1998
alopez: 8/25/1998
carol: 8/4/1998
terry: 8/3/1998
carol: 5/1/1998
mark: 4/7/1997
mark: 4/7/1996
mark: 7/26/1995
*RECORD*
*FIELD* NO
600686
*FIELD* TI
*600686 KARYOPHERIN ALPHA-1; KPNA1
;;SUPPRESSOR OF RNA POLYMERASE I MUTATION, S. CEREVISIAE, HOMOLOG OF;
read moreSRP1;;
RECOMBINATION ACTIVATING GENE COHORT 2; RCH2;;
IMPORTIN ALPHA-5
*FIELD* TX
CLONING
Cortes et al. (1994) used the 2-hybrid protein interaction systems to
isolate a protein that specifically interacts with RAG1 (179615). The
genes RAG1 and RAG2 (179616) are able to activate V(D)J recombination
when transfected into fibroblasts. Further, knockout mice for these 2
loci lack B and T cells. Several other ubiquitously expressed proteins
are thought to be recruited in the recombination process. Among these
are the genes affected in severe combined immune deficiency (e.g.,
600899) and genes involved in ds-DNA break repair. The human cDNA
identified by Cortes et al. (1994) encodes a 489-amino acid polypeptide
that shows striking similarity to the yeast SRP1 protein, a mutant
allele which can suppress a mutation of RNA polymerase I. The authors
obtained human and mouse cDNA sequences which are 98% identical as
proteins. When RAG1 and human SRP1 were cotransfected into 293T cells a
stable complex of the 2 was observed. The authors speculated that
because SRP1 appears to be bound to the nuclear envelope, the
interaction with RAG1 may serve to localize that protein to the envelope
as well.
GENE FUNCTION
Using an in vitro import assay based on permeabilized HeLa cells to
study the import substrate specificity of all ubiquitously expressed
importins, including KPNA1, 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.
By Western blot analysis and in vitro binding assays, Ma and Cao (2006)
found that nuclear translocation of STAT3 (102582) and STAT1 (600555) is
mediated by binding of human KPNA1 and KPNA6.
King et al. (2006) showed that integral inner nuclear membrane proteins
possess basic sequence motifs that resemble classical nuclear
localization signals. These sequences can mediate direct binding to
karyopherin-alpha and are essential for the passage of integral membrane
proteins to the inner nuclear membrane. Furthermore, karyopherin-alpha,
karyopherin-beta-1 (602738), and the Ran GTPase cycle are required for
inner nuclear membrane targeting, underscoring parallels between
mechanisms governing the targeting of integral inner nuclear membrane
proteins and soluble nuclear transport. King et al. (2006) also provided
evidence that specific nuclear pore complex proteins contribute to this
process, suggesting a role for signal-mediated alterations in the
nuclear pore complex to allow for passage of inner nuclear membrane
proteins along the pore membrane.
MAPPING
By fluorescence in situ hybridization, Ayala-Madrigal et al. (2000)
mapped the human KPNA1 gene to chromosome 3q21.
BIOCHEMICAL FEATURES
Conti et al. (1998) reported the crystal structure of a 50-kD fragment
of the 60-kD yeast karyopherin alpha, in the absence and presence of a
monopartite nuclear localization signal (NLS) peptide at 2.2-angstrom
and 2.8-angstrom resolution, respectively. The structure showed a tandem
array of 10 armadillo repeats, organized in a right-handed superhelix of
helices. Binding of the NLS peptide occurred at 2 sites within a helical
surface groove. The structure reveals the determinants of NLS
specificity and suggested a model for the recognition of bipartite NLSs.
*FIELD* RF
1. Ayala-Madrigal, M. L.; Doerr, S.; Ramirez-Duenas, M. L.; Hansmann,
I.: Assignment of karyopherin alpha 1 (KPNA1) to human chromosome
band 3q21 by in situ hybridization. Cytogenet. Cell Genet. 90: 58-59,
2000.
2. Conti, E.; Uy, M.; Leighton, L.; Blobel, G.; Kuriyan, J.: Crystallographic
analysis of the recognition of a nuclear localization signal by the
nuclear import factor karyopherin alpha. Cell 94: 193-204, 1998.
3. Cortes, P.; Ye, Z.-S.; Baltimore, D.: RAG-1 interacts with the
repeated amino acid motif of the human homologue of the yeast protein
SRP1. Proc. Nat. Acad. Sci. 91: 7633-7637, 1994.
4. King, M. C.; Lusk, C. P.; Blobel, G.: Karyopherin-mediated import
of integral inner nuclear membrane proteins. Nature 442: 1003-1007,
2006.
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. Ma, J.; Cao, X.: Regulation of Stat3 nuclear import by importin
alpha-5 and importin alpha-7 via two different functional sequence
elements. Cell. Signal. 18: 1117-1126, 2006.
*FIELD* CN
Patricia A. Hartz - updated: 11/14/2006
Ada Hamosh - updated: 10/24/2006
Carol A. Bocchini - updated: 2/12/2001
Stylianos E. Antonarakis - updated: 8/3/1998
Alan F. Scott - updated: 11/3/1995
*FIELD* CD
Alan F. Scott: 7/26/1995
*FIELD* ED
wwang: 11/14/2006
alopez: 11/1/2006
terry: 10/24/2006
ckniffin: 10/28/2004
carol: 2/12/2001
terry: 11/13/1998
alopez: 8/25/1998
carol: 8/4/1998
terry: 8/3/1998
carol: 5/1/1998
mark: 4/7/1997
mark: 4/7/1996
mark: 7/26/1995