Karyopherin alpha 2
Importin subunit alpha-2 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-2. 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 SGK,[4] PLAG1,[5] KPNB1,[6][7][8] RECQL,[9] ARL4A[10] and ITK.[11]
References
- ↑ Cuomo CA, Kirch SA, Gyuris J, Brent R, Oettinger MA (July 1994). "Rch1, a protein that specifically interacts with the RAG-1 recombination-activating protein". Proc Natl Acad Sci U S A 91 (13): 6156–60. doi:10.1073/pnas.91.13.6156. PMC 44157. PMID 8016130.
- ↑ Weis K, Mattaj IW, Lamond AI (June 1995). "Identification of hSRP1 alpha as a functional receptor for nuclear localization sequences". Science 268 (5213): 1049–53. doi:10.1126/science.7754385. PMID 7754385.
- ↑ "Entrez Gene: KPNA2 karyopherin alpha 2 (RAG cohort 1, importin alpha 1)".
- ↑ Maiyar, Anita C; Leong Meredith L L; Firestone Gary L (March 2003). "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". Mol. Biol. Cell (United States) 14 (3): 1221–39. doi:10.1091/mbc.E02-03-0170. ISSN 1059-1524. PMC 151592. PMID 12631736.
- ↑ Braem, Caroline V; Kas Koen, Meyen Eva, Debiec-Rychter Maria, Van De Ven Wim J M, Voz Marianne L (May 2002). "Identification of a karyopherin alpha 2 recognition site in PLAG1, which functions as a nuclear localization signal". J. Biol. Chem. (United States) 277 (22): 19673–8. doi:10.1074/jbc.M112112200. ISSN 0021-9258. PMID 11882654.
- ↑ Nagoshi, E; Yoneda Y (April 2001). "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". Mol. Cell. Biol. (United States) 21 (8): 2779–89. doi:10.1128/MCB.21.8.2779-2789.2001. ISSN 0270-7306. PMC 86908. PMID 11283257.
- ↑ Köhler, M; Speck C; Christiansen M; Bischoff F R; Prehn S; Haller H; Görlich D; Hartmann E (November 1999). "Evidence for distinct substrate specificities of importin alpha family members in nuclear protein import". Mol. Cell. Biol. (UNITED STATES) 19 (11): 7782–91. ISSN 0270-7306. PMC 84838. PMID 10523667.
- ↑ Kutay, U; Bischoff F R; Kostka S; Kraft R; Görlich D (September 1997). "Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor". Cell (UNITED STATES) 90 (6): 1061–71. doi:10.1016/S0092-8674(00)80372-4. ISSN 0092-8674. PMID 9323134.
- ↑ Seki, T; Tada S; Katada T; Enomoto T (May 1997). "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. (UNITED STATES) 234 (1): 48–53. doi:10.1006/bbrc.1997.6535. ISSN 0006-291X. PMID 9168958.
- ↑ Lin, C Y; Huang P H; Liao W L; Cheng H J; Huang C F; Kuo J C; Patton W A; Massenburg D; Moss J; Lee F J (December 2000). "ARL4, an ARF-like protein that is developmentally regulated and localized to nuclei and nucleoli". J. Biol. Chem. (UNITED STATES) 275 (48): 37815–23. doi:10.1074/jbc.M002470200. ISSN 0021-9258. PMID 10980193.
- ↑ Perez-Villar, J J; O'Day K; Hewgill D H; Nadler S G; Kanner S B (October 2001). "Nuclear localization of the tyrosine kinase Itk and interaction of its SH3 domain with karyopherin alpha (Rch1alpha)". Int. Immunol. (England) 13 (10): 1265–74. doi:10.1093/intimm/13.10.1265. ISSN 0953-8178. PMID 11581171.
Further reading
- Bukrinsky MI, Haffar OK (2004). "HIV-1 nuclear import: in search of a leader.". Front. Biosci. 2: d578–87. PMID 9366553.
- Bukrinsky MI, Haffar OK (1998). "HIV-1 nuclear import: matrix protein is back on center stage, this time together with Vpr.". Mol. Med. 4 (3): 138–43. PMC 2230352. PMID 9562972.
- Kino T, Pavlakis GN (2004). "Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1.". DNA Cell Biol. 23 (4): 193–205. doi:10.1089/104454904773819789. PMID 15142377.
- Teng SC, Wu KJ, Tseng SF et al. (2007). "Importin KPNA2, NBS1, DNA repair and tumorigenesis.". J. Mol. Histol. 37 (5-7): 293–9. doi:10.1007/s10735-006-9032-y. PMID 16752129.
- Bukrinsky MI, Sharova N, Dempsey MP et al. (1992). "Active nuclear import of human immunodeficiency virus type 1 preintegration complexes.". Proc. Natl. Acad. Sci. U.S.A. 89 (14): 6580–4. doi:10.1073/pnas.89.14.6580. PMC 49545. PMID 1631159.
- Sharova N, Bukrinskaya A (1991). "p17 and p17-containing gag precursors of input human immunodeficiency virus are transported into the nuclei of infected cells.". AIDS Res. Hum. Retroviruses 7 (3): 303–6. doi:10.1089/aid.1991.7.303. PMID 2064827.
- Di Marzio P, Choe S, Ebright M et al. (1996). "Mutational analysis of cell cycle arrest, nuclear localization and virion packaging of human immunodeficiency virus type 1 Vpr.". J. Virol. 69 (12): 7909–16. PMC 189735. PMID 7494303.
- Küssel P, Frasch M (1995). "Yeast Srp1, a nuclear protein related to Drosophila and mouse pendulin, is required for normal migration, division, and integrity of nuclei during mitosis.". Mol. Gen. Genet. 248 (3): 351–63. doi:10.1007/BF02191602. PMID 7565597.
- Gallay P, Swingler S, Song J et al. (1995). "HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix to the core domain of integrase.". Cell 83 (4): 569–76. doi:10.1016/0092-8674(95)90097-7. PMID 7585960.
- Moroianu J, Hijikata M, Blobel G, Radu A (1995). "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. 92 (14): 6532–6. doi:10.1073/pnas.92.14.6532. PMC 41552. PMID 7604027.
- Freed EO, Englund G, Martin MA (1995). "Role of the basic domain of human immunodeficiency virus type 1 matrix in macrophage infection.". J. Virol. 69 (6): 3949–54. PMC 189124. PMID 7745752.
- Gallay P, Swingler S, Aiken C, Trono D (1995). "HIV-1 infection of nondividing cells: C-terminal tyrosine phosphorylation of the viral matrix protein is a key regulator.". Cell 80 (3): 379–88. doi:10.1016/0092-8674(95)90488-3. PMID 7859280.
- von Schwedler U, Kornbluth RS, Trono D (1994). "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.". Proc. Natl. Acad. Sci. U.S.A. 91 (15): 6992–6. doi:10.1073/pnas.91.15.6992. PMC 44324. PMID 8041734.
- Heinzinger NK, Bukinsky MI, Haggerty SA et al. (1994). "The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells.". Proc. Natl. Acad. Sci. U.S.A. 91 (15): 7311–5. doi:10.1073/pnas.91.15.7311. PMC 44389. PMID 8041786.
- Bukrinsky MI, Haggerty S, Dempsey MP et al. (1993). "A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells.". Nature 365 (6447): 666–9. doi:10.1038/365666a0. PMID 8105392.
- Dubrovsky L, Ulrich P, Nuovo GJ et al. (1996). "Nuclear localization signal of HIV-1 as a novel target for therapeutic intervention.". Mol. Med. 1 (2): 217–30. PMC 2229944. PMID 8529100.
- Gallay P, Stitt V, Mundy C et al. (1996). "Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear import.". J. Virol. 70 (2): 1027–32. PMC 189908. PMID 8551560.
- Bukrinskaya AG, Ghorpade A, Heinzinger NK et al. (1996). "Phosphorylation-dependent human immunodeficiency virus type 1 infection and nuclear targeting of viral DNA.". Proc. Natl. Acad. Sci. U.S.A. 93 (1): 367–71. doi:10.1073/pnas.93.1.367. PMC 40239. PMID 8552640.
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