Transportin 1
| Transportin 1 | |||||||||||||
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 PDB rendering based on 1qbk. | |||||||||||||
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| Identifiers | |||||||||||||
| Symbols | TNPO1 ; IPO2; KPNB2; MIP; MIP1; TRN | ||||||||||||
| External IDs | OMIM: 602901 MGI: 2681523 HomoloGene: 5358 GeneCards: TNPO1 Gene | ||||||||||||
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| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 3842 | 238799 | |||||||||||
| Ensembl | ENSG00000083312 | ENSMUSG00000009470 | |||||||||||
| UniProt | Q92973 | Q8BFY9 | |||||||||||
| RefSeq (mRNA) | NM_002270 | NM_001048267 | |||||||||||
| RefSeq (protein) | NP_002261 | NP_001041732 | |||||||||||
| Location (UCSC) | Chr 5: 72.11 – 72.21 Mb | Chr 13: 98.84 – 98.93 Mb | |||||||||||
| PubMed search | |||||||||||||
Transportin-1 is a protein that in humans is encoded by the TNPO1 gene.[1][2][3]
Function
This gene encodes the beta subunit of the karyopherin receptor complex which interacts with nuclear localization signals to target nuclear proteins to the nucleus. The karyopherin receptor complex is a heterodimer of an alpha subunit which recognizes the nuclear localization signal and a beta subunit which docks the complex at nucleoporins. Alternate splicing of this gene results in two transcript variants encoding different proteins.[3]
Targets
Transportin 1 (TRN1) is part of the non-classical nuclear import pathway. In conjunction with the RanGTP hydroysis cascade TRN1 acts to import a selection of proteins into the nucleus of cells. These targets typically contain a PY-motif otherwise known as a M9 nuclear localisation signal. Well described examples include hnRNP A1.[4]
Clinical Significance
TRN1 has been implicated in the pathogenesis of two neurodegenerative diseases namely Amyotrophic lateral sclerosis and frontotemporal dementia.[5]
Interactions
Transportin 1 has been shown to interact with:
References
- ↑ Pollard VW, Michael WM, Nakielny S, Siomi MC, Wang F, Dreyfuss G (Dec 1996). "A novel receptor-mediated nuclear protein import pathway". Cell 86 (6): 985–94. doi:10.1016/S0092-8674(00)80173-7. PMID 8808633.
- ↑ Bonifaci N, Moroianu J, Radu A, Blobel G (Jun 1997). "Karyopherin beta2 mediates nuclear import of a mRNA binding protein". Proc. Natl. Acad. Sci. U.S.A. 94 (10): 5055–60. doi:10.1073/pnas.94.10.5055. PMC 24630. PMID 9144189.
- ↑ 3.0 3.1 "Entrez Gene: TNPO1 transportin 1".
- ↑ Dormann D, Rodde R, Edbauer D, Bentmann E, Fischer I, Hruscha A et al. (August 2010). "ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import". EMBO J. 29 (16): 2841–57. doi:10.1038/emboj.2010.143. PMC 2924641. PMID 20606625.
- ↑ Brelstaff J, Lashley T, Holton JL, Lees AJ, Rossor MN, Bandopadhyay R et al. (November 2011). "Transportin1: a marker of FTLD-FUS". Acta Neuropathol. 122 (5): 591–600. doi:10.1007/s00401-011-0863-6. PMID 21847626.
- ↑ Cai Y, Miao SY, Wang LF (October 2001). "[Determination of the binding site of testis-specific nucleoporin BS-63 to transportin (karopherin beta 2) and the proof of their combination in vitro]". Zhongguo Yi Xue Ke Xue Yuan Xue Bao (in Chinese) 23 (5): 462–6. PMID 12905863.
- ↑ Chook YM, Blobel G (May 1999). "Structure of the nuclear transport complex karyopherin-beta2-Ran x GppNHp". Nature 399 (6733): 230–7. doi:10.1038/20375. PMID 10353245.
- ↑ Shamsher MK, Ploski J, Radu A (October 2002). "Karyopherin beta 2B participates in mRNA export from the nucleus". Proc. Natl. Acad. Sci. U.S.A. 99 (22): 14195–9. doi:10.1073/pnas.212518199. PMC 137860. PMID 12384575.
Further reading
- Bukrinsky MI, Haffar OK (1997). "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.
- Bukrinsky MI, Sharova N, Dempsey MP, Stanwick TL, Bukrinskaya AG, Haggerty S 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.
- 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.
- Bukrinsky MI, Haggerty S, Dempsey MP, Sharova N, Adzhubel A, Spitz L 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.
- Michael WM, Choi M, Dreyfuss G (1995). "A nuclear export signal in hnRNP A1: a signal-mediated, temperature-dependent nuclear protein export pathway". Cell 83 (3): 415–22. doi:10.1016/0092-8674(95)90119-1. PMID 8521471.
- Nakielny S, Siomi MC, Siomi H, Michael WM, Pollard V, Dreyfuss G (1996). "Transportin: nuclear transport receptor of a novel nuclear protein import pathway". Exp. Cell Res. 229 (2): 261–6. doi:10.1006/excr.1996.0369. PMID 8986607.
- Fridell RA, Truant R, Thorne L, Benson RE, Cullen BR (1997). "Nuclear import of hnRNP A1 is mediated by a novel cellular cofactor related to karyopherin-beta". J. Cell. Sci. 110 ( Pt 11) (11): 1325–31. PMID 9202393.
- Gallay P, Hope T, Chin D, Trono D (1997). "HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway". Proc. Natl. Acad. Sci. U.S.A. 94 (18): 9825–30. doi:10.1073/pnas.94.18.9825. PMC 23276. PMID 9275210.
- Siomi MC, Eder PS, Kataoka N, Wan L, Liu Q, Dreyfuss G (1997). "Transportin-mediated nuclear import of heterogeneous nuclear RNP proteins". J. Cell Biol. 138 (6): 1181–92. doi:10.1083/jcb.138.6.1181. PMC 2132560. PMID 9298975.
- Henderson BR, Percipalle P (1997). "Interactions between HIV Rev and nuclear import and export factors: the Rev nuclear localisation signal mediates specific binding to human importin-beta". J. Mol. Biol. 274 (5): 693–707. doi:10.1006/jmbi.1997.1420. PMID 9405152.
- Efthymiadis A, Briggs LJ, Jans DA (1998). "The HIV-1 Tat nuclear localization sequence confers novel nuclear import properties". J. Biol. Chem. 273 (3): 1623–8. doi:10.1074/jbc.273.3.1623. PMID 9430704.
- Vodicka MA, Koepp DM, Silver PA, Emerman M (1998). "HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection". Genes Dev. 12 (2): 175–85. doi:10.1101/gad.12.2.175. PMC 316441. PMID 9436978.
- Popov S, Rexach M, Zybarth G, Reiling N, Lee MA, Ratner L et al. (1998). "Viral protein R regulates nuclear import of the HIV-1 pre-integration complex". EMBO J. 17 (4): 909–17. doi:10.1093/emboj/17.4.909. PMC 1170440. PMID 9463369.
- Popov S, Rexach M, Ratner L, Blobel G, Bukrinsky M (1998). "Viral protein R regulates docking of the HIV-1 preintegration complex to the nuclear pore complex". J. Biol. Chem. 273 (21): 13347–52. doi:10.1074/jbc.273.21.13347. PMID 9582382.
- Fouchier RA, Meyer BE, Simon JH, Fischer U, Albright AV, González-Scarano F et al. (1998). "Interaction of the human immunodeficiency virus type 1 Vpr protein with the nuclear pore complex". J. Virol. 72 (7): 6004–13. PMC 110405. PMID 9621063. Vancouver style error (help)
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