You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP08457
Secondary Accession Numbers
  • 14169
Name Importin subunit alpha-2
Synonyms
  1. Karyopherin subunit alpha-2
  2. RAG cohort protein 1
  3. SRP1-alpha
Gene Name KPNA2
Protein Type Unknown
Biological Properties
General Function Involved in binding
Specific Function Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran- dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
intracellular part
cytoplasm
organelle
membrane-bounded organelle
intracellular membrane-bounded organelle
nucleus
nuclear pore
organelle part
intracellular organelle part
nuclear part
Function
binding
protein transporter activity
transporter activity
substrate-specific transporter activity
Process
establishment of localization
transport
protein transport
protein import into nucleus
intracellular protein transport
protein targeting
Cellular Location
  1. Nucleus
  2. Cytoplasm
Gene Properties
Chromosome Location Chromosome:1
Locus 17q24.2
SNPs KPNA2
Gene Sequence
>1590 bp
ATGTCCACCAACGAGAATGCTAATACACCAGCTGCCCGTCTTCACAGATTCAAGAACAAG
GGAAAAGACAGTACAGAAATGAGGCGTCGCAGAATAGAGGTCAATGTGGAGCTGAGGAAA
GCTAAGAAGGATGACCAGATGCTGAAGAGGAGAAATGTAAGCTCATTTCCTGATGATGCT
ACTTCTCCGCTGCAGGAAAACCGCAACAACCAGGGCACTGTAAATTGGTCTGTTGATGAC
ATTGTCAAAGGCATAAATAGCAGCAATGTGGAAAATCAGCTCCAAGCTACTCAAGCTGCC
AGGAAACTACTTTCCAGAGAAAAACAGCCCCCCATAGACAACATAATCCGGGCTGGTTTG
ATTCCGAAATTTGTGTCCTTCTTGGGCAGAACTGATTGTAGTCCCATTCAGTTTGAATCT
GCTTGGGCACTCACTAACATTGCTTCTGGGACATCAGAACAAACCAAGGCTGTGGTAGAT
GGAGGTGCCATCCCAGCATTCATTTCTCTGTTGGCATCTCCCCATGCTCACATCAGTGAA
CAAGCTGTCTGGGCTCTAGGAAACATTGCAGGTGATGGCTCAGTGTTCCGAGACTTGGTT
ATTAAGTACGGTGCAGTTGACCCACTGTTGGCTCTCCTTGCAGTTCCTGATATGTCATCT
TTAGCATGTGGCTACTTACGTAATCTTACCTGGACACTTTCTAATCTTTGCCGCAACAAG
AATCCTGCACCCCCGATAGATGCTGTTGAGCAGATTCTTCCTACCTTAGTTCGGCTCCTG
CATCATGATGATCCAGAAGTGTTAGCAGATACCTGCTGGGCTATTTCCTACCTTACTGAT
GGTCCAAATGAACGAATTGGCATGGTGGTGAAAACAGGAGTTGTGCCCCAACTTGTGAAG
CTTCTAGGAGCTTCTGAATTGCCAATTGTGACTCCTGCCCTAAGAGCCATAGGGAATATT
GTCACTGGTACAGATGAACAGACTCAGGTTGTGATTGATGCAGGAGCACTCGCCGTCTTT
CCCAGCCTGCTCACCAACCCCAAAACTAACATTCAGAAGGAAGCTACGTGGACAATGTCA
AACATCACAGCCGGCCGCCAGGACCAGATACAGCAAGTTGTGAATCATGGATTAGTCCCA
TTCCTTGTCAGTGTTCTCTCTAAGGCAGATTTTAAGACACAAAAGGAAGCTGTGTGGGCC
GTGACCAACTATACCAGTGGTGGAACAGTTGAACAGATTGTGTACCTTGTTCACTGTGGC
ATAATAGAACCGTTGATGAACCTCTTAACTGCAAAAGATACCAAGATTATTCTGGTTATC
CTGGATGCCATTTCAAATATCTTTCAGGCTGCTGAGAAACTAGGTGAAACTGAGAAACTT
AGTATAATGATTGAAGAATGTGGAGGCTTAGACAAAATTGAAGCTCTACAAAACCATGAA
AATGAGTCTGTGTATAAGGCTTCGTTAAGCTTAATTGAGAAGTATTTCTCTGTAGAGGAA
GAGGAAGATCAAAACGTTGTACCAGAAACTACCTCTGAAGGCTACACTTTCCAAGTTCAG
GATGGGGCTCCTGGGACCTTTAACTTTTAG
Protein Properties
Number of Residues 529
Molecular Weight 57861.4
Theoretical pI 5.05
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Importin subunit alpha-2
MSTNENANTPAARLHRFKNKGKDSTEMRRRRIEVNVELRKAKKDDQMLKRRNVSSFPDDA
TSPLQENRNNQGTVNWSVDDIVKGINSSNVENQLQATQAARKLLSREKQPPIDNIIRAGL
IPKFVSFLGRTDCSPIQFESAWALTNIASGTSEQTKAVVDGGAIPAFISLLASPHAHISE
QAVWALGNIAGDGSVFRDLVIKYGAVDPLLALLAVPDMSSLACGYLRNLTWTLSNLCRNK
NPAPPIDAVEQILPTLVRLLHHDDPEVLADTCWAISYLTDGPNERIGMVVKTGVVPQLVK
LLGASELPIVTPALRAIGNIVTGTDEQTQVVIDAGALAVFPSLLTNPKTNIQKEATWTMS
NITAGRQDQIQQVVNHGLVPFLVSVLSKADFKTQKEAVWAVTNYTSGGTVEQIVYLVHCG
IIEPLMNLLTAKDTKIILVILDAISNIFQAAEKLGETEKLSIMIEECGGLDKIEALQNHE
NESVYKASLSLIEKYFSVEEEEDQNVVPETTSEGYTFQVQDGAPGTFNF
GenBank ID Protein 15865453
UniProtKB/Swiss-Prot ID P52292
UniProtKB/Swiss-Prot Entry Name IMA2_HUMAN
PDB IDs
GenBank Gene ID AJ303086
GeneCard ID KPNA2
GenAtlas ID KPNA2
HGNC ID HGNC:6395
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  3. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  4. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976 ]
  5. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  6. Yu LR, Zhu Z, Chan KC, Issaq HJ, Dimitrov DS, Veenstra TD: Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra. J Proteome Res. 2007 Nov;6(11):4150-62. Epub 2007 Oct 9. [PubMed:17924679 ]
  7. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  8. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. [PubMed:16964243 ]
  9. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. [PubMed:18220336 ]
  10. Wang B, Malik R, Nigg EA, Korner R: Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis. Anal Chem. 2008 Dec 15;80(24):9526-33. doi: 10.1021/ac801708p. [PubMed:19007248 ]
  11. Harris RA, Yang A, Stein RC, Lucy K, Brusten L, Herath A, Parekh R, Waterfield MD, O'Hare MJ, Neville MA, Page MJ, Zvelebil MJ: Cluster analysis of an extensive human breast cancer cell line protein expression map database. Proteomics. 2002 Feb;2(2):212-23. [PubMed:11840567 ]
  12. Nousiainen M, Sillje HH, Sauer G, Nigg EA, Korner R: Phosphoproteome analysis of the human mitotic spindle. Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5391-6. Epub 2006 Mar 24. [PubMed:16565220 ]
  13. Moroianu J, Hijikata M, Blobel G, Radu A: Mammalian karyopherin alpha 1 beta and alpha 2 beta heterodimers: alpha 1 or alpha 2 subunit binds nuclear localization signal and beta subunit interacts with peptide repeat-containing nucleoporins. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6532-6. [PubMed:7604027 ]
  14. Popov S, Rexach M, Zybarth G, Reiling N, Lee MA, Ratner L, Lane CM, Moore MS, Blobel G, Bukrinsky M: Viral protein R regulates nuclear import of the HIV-1 pre-integration complex. EMBO J. 1998 Feb 16;17(4):909-17. [PubMed:9463369 ]
  15. Weis K, Mattaj IW, Lamond AI: Identification of hSRP1 alpha as a functional receptor for nuclear localization sequences. Science. 1995 May 19;268(5213):1049-53. [PubMed:7754385 ]
  16. Dorr SN, Schlicker MN, Hansmann IN: Genomic structure of karyopherin alpha2 ( KPNA2) within a low-copy repeat on chromosome 17q23-q24 and mutation analysis in patients with Russell-Silver syndrome. Hum Genet. 2001 Nov;109(5):479-86. Epub 2001 Oct 3. [PubMed:11735022 ]
  17. Cuomo CA, Kirch SA, Gyuris J, Brent R, Oettinger MA: Rch1, a protein that specifically interacts with the RAG-1 recombination-activating protein. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6156-60. [PubMed:8016130 ]
  18. Weis K, Ryder U, Lamond AI: The conserved amino-terminal domain of hSRP1 alpha is essential for nuclear protein import. EMBO J. 1996 Apr 15;15(8):1818-25. [PubMed:8617227 ]
  19. Kutay U, Bischoff FR, Kostka S, Kraft R, Gorlich D: Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor. Cell. 1997 Sep 19;90(6):1061-71. [PubMed:9323134 ]
  20. Herold A, Truant R, Wiegand H, Cullen BR: Determination of the functional domain organization of the importin alpha nuclear import factor. J Cell Biol. 1998 Oct 19;143(2):309-18. [PubMed:9786944 ]
  21. Braem CV, Kas K, Meyen E, Debiec-Rychter M, Van De Ven WJ, Voz ML: Identification of a karyopherin alpha 2 recognition site in PLAG1, which functions as a nuclear localization signal. J Biol Chem. 2002 May 31;277(22):19673-8. Epub 2002 Mar 6. [PubMed:11882654 ]
  22. Tseng SF, Chang CY, Wu KJ, Teng SC: Importin KPNA2 is required for proper nuclear localization and multiple functions of NBS1. J Biol Chem. 2005 Nov 25;280(47):39594-600. Epub 2005 Sep 27. [PubMed:16188882 ]
  23. Cingolani G, Petosa C, Weis K, Muller CW: Structure of importin-beta bound to the IBB domain of importin-alpha. Nature. 1999 May 20;399(6733):221-9. [PubMed:10353244 ]