Importin subunit alpha-1 explained

Importin subunit alpha-1 is a protein that in humans is encoded by the KPNA2 gene.^{[1] [2]}

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 are members of the alpha importin family of karyopherins such as importin subunit alpha-1. 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), which bind to the NLS. KPNA2 protein interacts with the NLSs of DNA helicase Q1 and SV40 T antigen and may be involved in the nuclear transport of proteins. KPNA2 also may play a role in V(D)J recombination^[3]

Interactions

Karyopherin alpha 2 has been shown to interact with:

• ARL4A^[4]
• ITK,^[5]
• KPNB1,^{[6] [7] [8]}
• PLAG1,^[9]
• RECQL,^[10] and
• SGK.^[11]

Further reading

• Bukrinsky MI, Haffar OK . HIV-1 nuclear import: in search of a leader . Frontiers in Bioscience . 2 . 4. d578-87 . Dec 1997 . 9366553 . 10.2741/A213 . free .
• Bukrinsky MI, Haffar OK . HIV-1 nuclear import: matrix protein is back on center stage, this time together with Vpr . Molecular Medicine . 4 . 3 . 138–43 . Mar 1998 . 9562972 . 2230352 . 10.1007/BF03401911.
• Kino T, Pavlakis GN . Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1 . DNA and Cell Biology . 23 . 4 . 193–205 . Apr 2004 . 15142377 . 10.1089/104454904773819789 .
• Teng SC, Wu KJ, Tseng SF, Wong CW, Kao L . Importin KPNA2, NBS1, DNA repair and tumorigenesis . Journal of Molecular Histology . 37 . 5–7 . 293–9 . Sep 2006 . 16752129 . 10.1007/s10735-006-9032-y . 7281949 .
• Bukrinsky MI, Sharova N, Dempsey MP, Stanwick TL, Bukrinskaya AG, Haggerty S, Stevenson M . Active nuclear import of human immunodeficiency virus type 1 preintegration complexes . Proceedings of the National Academy of Sciences of the United States of America . 89 . 14 . 6580–4 . Jul 1992 . 1631159 . 49545 . 10.1073/pnas.89.14.6580 . 1992PNAS...89.6580B . free .
• Sharova N, Bukrinskaya A . p17 and p17-containing gag precursors of input human immunodeficiency virus are transported into the nuclei of infected cells . AIDS Research and Human Retroviruses . 7 . 3 . 303–6 . Mar 1991 . 2064827 . 10.1089/aid.1991.7.303 .
• Di Marzio P, Choe S, Ebright M, Knoblauch R, Landau NR . Mutational analysis of cell cycle arrest, nuclear localization and virion packaging of human immunodeficiency virus type 1 Vpr . Journal of Virology . 69 . 12 . 7909–16 . Dec 1995 . 7494303 . 189735 . 10.1128/JVI.69.12.7909-7916.1995.
• Küssel P, Frasch M . Yeast Srp1, a nuclear protein related to Drosophila and mouse pendulin, is required for normal migration, division, and integrity of nuclei during mitosis . Molecular & General Genetics . 248 . 3 . 351–63 . Aug 1995 . 7565597 . 10.1007/BF02191602 . 24877825 .
• Gallay P, Swingler S, Song J, Bushman F, Trono D . HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix to the core domain of integrase . Cell . 83 . 4 . 569–76 . Nov 1995 . 7585960 . 10.1016/0092-8674(95)90097-7 . 15536328 . free .
• 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 . Proceedings of the National Academy of Sciences of the United States of America . 92 . 14 . 6532–6 . Jul 1995 . 7604027 . 41552 . 10.1073/pnas.92.14.6532 . 1995PNAS...92.6532M . free .
• Freed EO, Englund G, Martin MA . Role of the basic domain of human immunodeficiency virus type 1 matrix in macrophage infection . Journal of Virology . 69 . 6 . 3949–54 . Jun 1995 . 7745752 . 189124 . 10.1128/JVI.69.6.3949-3954.1995.
• Gallay P, Swingler S, Aiken C, Trono D . HIV-1 infection of nondividing cells: C-terminal tyrosine phosphorylation of the viral matrix protein is a key regulator . Cell . 80 . 3 . 379–88 . Feb 1995 . 7859280 . 10.1016/0092-8674(95)90488-3 . 15064293 . free .
• von Schwedler U, Kornbluth RS, Trono D . The nuclear localization signal of the matrix protein of human immunodeficiency virus type 1 allows the establishment of infection in macrophages and quiescent T lymphocytes . Proceedings of the National Academy of Sciences of the United States of America . 91 . 15 . 6992–6 . Jul 1994 . 8041734 . 44324 . 10.1073/pnas.91.15.6992 . 1994PNAS...91.6992V . free .
• Howard E. Gendelman . Heinzinger NK, Bukrinsky MI, Haggerty SA, Ragland AM, Kewalramani V, Lee MA, Gendelman HE, Ratner L, Stevenson M, Emerman M . The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells . Proceedings of the National Academy of Sciences of the United States of America . 91 . 15 . 7311–5 . Jul 1994 . 8041786 . 44389 . 10.1073/pnas.91.15.7311 . 1994PNAS...91.7311H . free .
• Bukrinsky MI, Haggerty S, Dempsey MP, Sharova N, Adzhubel A, Spitz L, Lewis P, Goldfarb D, Emerman M, Stevenson M . A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells . Nature . 365 . 6447 . 666–9 . Oct 1993 . 8105392 . 10.1038/365666a0 . 9524217 . 1993Natur.365..666B . 25678 .
• Dubrovsky L, Ulrich P, Nuovo GJ, Manogue KR, Cerami A, Bukrinsky M . Nuclear localization signal of HIV-1 as a novel target for therapeutic intervention . Molecular Medicine . 1 . 2 . 217–30 . Jan 1995 . 8529100 . 2229944 . 10.1007/BF03401569.
• Gallay P, Stitt V, Mundy C, Oettinger M, Trono D . Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import . Journal of Virology . 70 . 2 . 1027–32 . Feb 1996 . 8551560 . 189908 . 10.1128/JVI.70.2.1027-1032.1996.
• Bukrinskaya AG, Ghorpade A, Heinzinger NK, Smithgall TE, Lewis RE, Stevenson M . Phosphorylation-dependent human immunodeficiency virus type 1 infection and nuclear targeting of viral DNA . Proceedings of the National Academy of Sciences of the United States of America . 93 . 1 . 367–71 . Jan 1996 . 8552640 . 40239 . 10.1073/pnas.93.1.367 . 1996PNAS...93..367B . free .

Notes and References

1. Cuomo CA, Kirch SA, Gyuris J, Brent R, Oettinger MA . Rch1, a protein that specifically interacts with the RAG-1 recombination-activating protein . Proceedings of the National Academy of Sciences of the United States of America . 91 . 13 . 6156–60 . Jun 1994 . 8016130 . 44157 . 10.1073/pnas.91.13.6156 . 1994PNAS...91.6156C . free .
2. Weis K, Mattaj IW, Lamond AI . Identification of hSRP1 alpha as a functional receptor for nuclear localization sequences . Science . 268 . 5213 . 1049–53 . May 1995 . 7754385 . 10.1126/science.7754385 . 1995Sci...268.1049W .
3. Web site: Entrez Gene: KPNA2 karyopherin alpha 2 (RAG cohort 1, importin alpha 1).
4. Lin CY, Huang PH, Liao WL, Cheng HJ, Huang CF, Kuo JC, Patton WA, Massenburg D, Moss J, Lee FJ . ARL4, an ARF-like protein that is developmentally regulated and localized to nuclei and nucleoli . The Journal of Biological Chemistry . 275 . 48 . 37815–23 . Dec 2000 . 10980193 . 10.1074/jbc.M002470200 . free.
5. Perez-Villar JJ, O'Day K, Hewgill DH, Nadler SG, Kanner SB . Nuclear localization of the tyrosine kinase Itk and interaction of its SH3 domain with karyopherin alpha (Rch1alpha) . . 13 . 10 . 1265–74 . Oct 2001 . 11581171 . 10.1093/intimm/13.10.1265. free .
6. Nagoshi E, Yoneda Y . Dimerization of sterol regulatory element-binding protein 2 via the helix-loop-helix-leucine zipper domain is a prerequisite for its nuclear localization mediated by importin beta . Molecular and Cellular Biology . 21 . 8 . 2779–89 . Apr 2001 . 11283257 . 86908 . 10.1128/MCB.21.8.2779-2789.2001 .
7. Köhler M, Speck C, Christiansen M, Bischoff FR, Prehn S, Haller H, Görlich D, Hartmann E . Evidence for distinct substrate specificities of importin alpha family members in nuclear protein import . Molecular and Cellular Biology . 19 . 11 . 7782–91 . Nov 1999 . 10523667 . 84838 . 10.1128/mcb.19.11.7782.
8. Kutay U, Bischoff FR, Kostka S, Kraft R, Görlich D . Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor . Cell . 90 . 6 . 1061–71 . Sep 1997 . 9323134 . 10.1016/s0092-8674(00)80372-4. 16092404 . free .
9. 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 . The Journal of Biological Chemistry . 277 . 22 . 19673–8 . May 2002 . 11882654 . 10.1074/jbc.M112112200 . free .
10. 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 . Biochemical and Biophysical Research Communications . 234 . 1 . 48–53 . May 1997 . 9168958 . 10.1006/bbrc.1997.6535 .
11. Maiyar AC, Leong ML, Firestone GL . Importin-alpha mediates the regulated nuclear targeting of serum- and glucocorticoid-inducible protein kinase (Sgk) by recognition of a nuclear localization signal in the kinase central domain . Molecular Biology of the Cell . 14 . 3 . 1221–39 . Mar 2003 . 12631736 . 151592 . 10.1091/mbc.E02-03-0170 .