ID IMA2_HUMAN Reviewed; 529 AA. AC P52292; Q9BRU5; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 13-OCT-2009, entry version 119. DE RecName: Full=Importin subunit alpha-2; DE AltName: Full=Karyopherin subunit alpha-2; DE AltName: Full=SRP1-alpha; DE AltName: Full=RAG cohort protein 1; 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 MEDLINE=95273975; 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 MEDLINE=21592389; 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]. RC TISSUE=Bone marrow; 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 [4] 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 [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 33-529. RC TISSUE=Cervix carcinoma; RX MEDLINE=94286596; 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 [6] RP FUNCTIONAL SUBSTITUTION OF ALPHA-1 BY ALPHA-2 SUBUNIT. RX MEDLINE=95327681; 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 [7] RP IDENTIFICATION OF IBB DOMAIN. RX MEDLINE=96203102; 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 [8] RP IDENTIFICATION IN A COMPLEX WITH RAN AND CSE1L. RX MEDLINE=97462907; 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 [9] 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 [10] 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 [11] 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 [12] RP MASS SPECTROMETRY. RC TISSUE=Mammary cancer; RX MEDLINE=21829512; 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 [13] 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 [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, AND MASS RP SPECTROMETRY. RC TISSUE=Epithelium; 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-490, AND MASS RP SPECTROMETRY. RC TISSUE=Epithelium; 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, AND MASS RP SPECTROMETRY. RC TISSUE=Epithelium; RX PubMed=16565220; DOI=10.1073/pnas.0507066103; RA Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R.; RT "Phosphoproteome analysis of the human mitotic spindle."; RL Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, AND MASS RP SPECTROMETRY. RC TISSUE=Epithelium; RX PubMed=17924679; DOI=10.1021/pr070152u; RA Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.; RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa RT cells and high confident phosphopeptide identification by cross- RT validation of MS/MS and MS/MS/MS spectra."; RL J. Proteome Res. 6:4150-4162(2007). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-61 AND SER-62, AND MASS RP SPECTROMETRY. RX PubMed=19007248; DOI=10.1021/ac801708p; RA Wang B., Malik R., Nigg E.A., Korner R.; RT "Evaluation of the low-specificity protease elastase for large-scale RT phosphoproteome analysis."; RL Anal. Chem. 80:9526-9533(2008). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, AND MASS RP SPECTROMETRY. 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 [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-490, AND MASS RP SPECTROMETRY. 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 [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-490, AND MASS RP SPECTROMETRY. 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 [22] RP IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. RA Colinge J., Superti-Furga G., Bennett K.L.; RL Submitted (OCT-2008) to UniProtKB. RN [23] 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: Forms a complex with importin subunit beta-1. Found in a CC complex with CSE1L/XPO2, Ran and KPNA2. Interacts with CSE1L/XPO2 CC and NBN. Interacts with ANP32E (By similarity). Interacts with CC HIV-1 Vpr and PLAG1. CC -!- INTERACTION: CC P38398:BRCA1; NbExp=1; IntAct=EBI-349938, EBI-349905; 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 https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U28386; AAA69957.1; -; mRNA. DR EMBL; AJ303086; CAC83080.1; -; Genomic_DNA. DR EMBL; BC005978; AAH05978.1; -; mRNA. DR EMBL; U09559; AAA65700.1; -; mRNA. DR IPI; IPI00002214; -. DR PIR; A56516; A56516. DR RefSeq; NP_002257.1; -. DR UniGene; Hs.594238; -. DR UniGene; Hs.632749; -. 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 PDBsum; 1EFX; -. DR PDBsum; 1QGK; -. DR PDBsum; 1QGR; -. DR PDBsum; 3FEX; -. DR PDBsum; 3FEY; -. DR SMR; P52292; 75-498. DR DIP; DIP:6205N; -. DR IntAct; P52292; 10. DR STRING; P52292; -. DR PhosphoSite; P52292; -. DR SWISS-2DPAGE; P52292; -. DR PeptideAtlas; P52292; -. DR PRIDE; P52292; -. DR Ensembl; ENST00000330459; ENSP00000332455; ENSG00000182481; Homo sapiens. DR GeneID; 3838; -. DR KEGG; hsa:3838; -. DR UCSC; uc002jgk.1; human. DR CTD; 3838; -. DR GeneCards; GC17M8C0097; -. DR GeneCards; GC17P063463; -. DR H-InvDB; HIX0021306; -. DR H-InvDB; HIX0023282; -. DR HGNC; HGNC:6395; KPNA2. DR HPA; CAB015460; -. DR MIM; 600685; gene. DR PharmGKB; PA30186; -. DR HOGENOM; P52292; -. DR HOVERGEN; P52292; -. DR OMA; P52292; CRNKNPP. DR Pathway_Interaction_DB; smad2_3pathway; Regulation of cytoplasmic and nuclear SMAD2/3 signaling. DR Pathway_Interaction_DB; nfat_3pathway; Role of Calcineurin-dependent NFAT signaling in lymphocytes. DR NextBio; 15087; -. DR Bgee; P52292; -. DR CleanEx; HS_KPNA2; -. DR Genevestigator; P52292; -. DR GermOnline; ENSG00000182481; Homo sapiens. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0005643; C:nuclear pore; IEA:InterPro. DR GO; GO:0005654; C:nucleoplasm; TAS:ProtInc. DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB. DR GO; GO:0008139; F:nuclear localization sequence binding; TAS:ProtInc. DR GO; GO:0008565; F:protein transporter activity; IEA:InterPro. DR GO; GO:0006259; P:DNA metabolic process; TAS:ProtInc. DR GO; GO:0000085; P:G2 phase of mitotic cell cycle; TAS:ProtInc. DR GO; GO:0044419; P:interspecies interaction between organisms; IEA:UniProtKB-KW. DR GO; GO:0000072; P:M phase specific microtubule process; TAS:ProtInc. DR GO; GO:0006607; P:NLS-bearing substrate import into nucleus; TAS:ProtInc. DR GO; GO:0000018; P:regulation of DNA recombination; TAS:ProtInc. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR000225; Armadillo. DR InterPro; IPR002652; Importin-a-like_IBB-bd. DR Gene3D; G3DSA:1.25.10.10; ARM-like; 1. DR Gene3D; G3DSA:1.20.5.690; Importin-a-like_IBB-bd; 1. DR Pfam; PF00514; Arm; 8. DR Pfam; PF01749; IBB; 1. DR SMART; SM00185; ARM; 8. 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; Repeat; Transport. FT INIT_MET 1 1 Removed. FT CHAIN 2 529 Importin subunit alpha-2. 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 24 24 Phosphoserine. FT MOD_RES 61 61 Phosphothreonine. FT MOD_RES 62 62 Phosphoserine. FT MOD_RES 490 490 Phosphoserine. FT VARIANT 165 165 P -> R (in dbSNP:rs11545989). FT /FTId=VAR_013137. FT VARIANT 430 430 T -> P (in dbSNP:rs1059538). FT /FTId=VAR_014453. FT CONFLICT 157 157 A -> V (in Ref. 3; AAH05978). FT CONFLICT 453 453 K -> N (in Ref. 3; AAH05978). FT HELIX 14 16 FT TURN 18 21 FT HELIX 24 27 FT HELIX 30 48 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 //