Transportin-3

Definition:

Importin, which transports target proteins into the nucleus. Specifically mediates the nuclear import of splicing factor serine/arginine (SR) proteins, such as RBM4, SFRS1 and SFRS2, by recognizing phosphorylated SR domains. Also mediates the nuclear import of serine/arginine (SR) protein CPSF6, independently of CPSF6 phosphorylation. The nuclear import process is regulated by the small GTPase Ran that partitions between cytoplasm and nucleus in the predominantly GDP- and GTP-bound form, respectively. Importin associates with target cargo proteins in the cytoplasm, and the competitive binding of GTP-bound Ran induces the release of cargos in the nucleus.; (Microbial infection) Involved in immunodeficiency virus (HIV-1) infection by importing the pre-integration complex (PIC) into the nucleus. Required for a nuclear maturation step of HIV-1 prior to integration.

References:

[1]. Frauke Christ, et al. Transportin-SR2 imports HIV into the nucleus. Curr Biol. 2008 Aug 26;18(16):1192-202. [Content Brief]

[2]. N Kataoka, et al. Transportin-SR, a nuclear import receptor for SR proteins. J Cell Biol. 1999 Jun 14;145(6):1145-52. [Content Brief]

[3]. Ming-Chih Lai, et al. A novel splicing regulator shares a nuclear import pathway with SR proteins. EMBO J. 2003 Mar 17;22(6):1359-69. [Content Brief]

[4]. M C Lai, et al. Transportin-SR2 mediates nuclear import of phosphorylated SR proteins. Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10154-9. [Content Brief]

[5]. Jonas Demeulemeester, et al. Inhibitors of the integrase-transportin-SR2 interaction block HIV nuclear import. Retrovirology. 2018 Jan 12;15(1):5. [Content Brief]

[6]. Lihong Zhou, et al. Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. PLoS Pathog. 2011 Aug;7(8):e1002194. [Content Brief]

[7]. Oliver Taltynov, et al. Interaction of transportin-SR2 with Ras-related nuclear protein (Ran) GTPase. J Biol Chem. 2013 Aug 30;288(35):25603-25613. [Content Brief]

[8]. Goedele N Maertens, et al. Structural basis for nuclear import of splicing factors by human Transportin 3. Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2728-33. [Content Brief]

[9]. M C Lai, et al. A human importin-beta family protein, transportin-SR2, interacts with the phosphorylated RS domain of SR proteins. J Biol Chem. 2000 Mar 17;275(11):7950-7. [Content Brief]

[10]. Jose Carlos Valle-Casuso, et al. TNPO3 is required for HIV-1 replication after nuclear import but prior to integration and binds the HIV-1 core. J Virol. 2012 May;86(10):5931-6. [Content Brief]

[11]. Sooin Jang, et al. Differential role for phosphorylation in alternative polyadenylation function versus nuclear import of SR-like protein CPSF6. Nucleic Acids Res. 2019 May 21;47(9):4663-4683. [Content Brief]

[12]. Sara Rodríguez-Mora, et al. The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection. PLoS Pathog. 2019 Aug 29;15(8):e1007958. [Content Brief]

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