Transportin 1

{{cs1 config|name-list-style=vanc}} {{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} '''Transportin-1''' (or '''Importin-β''' '''2''') is a protein that in humans is encoded by the ''TNPO1'' gene.<ref name="pmid8808633">{{cite journal | vauthors = Pollard VW, Michael WM, Nakielny S, Siomi MC, Wang F, Dreyfuss G | title = A novel receptor-mediated nuclear protein import pathway | journal = Cell | volume = 86 | issue = 6 | pages = 985–94 | date = Dec 1996 | pmid = 8808633 | doi = 10.1016/S0092-8674(00)80173-7 | s2cid = 15666255 | doi-access = free }}</ref><ref name="pmid9144189">{{cite journal | vauthors = Bonifaci N, Moroianu J, Radu A, Blobel G | title = Karyopherin beta2 mediates nuclear import of a mRNA binding protein | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 10 | pages = 5055–60 | date = Jun 1997 | pmid = 9144189 | pmc = 24630 | doi = 10.1073/pnas.94.10.5055 | bibcode = 1997PNAS...94.5055B | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TNPO1 transportin 1| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=3842}}</ref>

== Function == This protein is a karyopherin which interacts with nuclear localization sequence to target nuclear proteins to the nucleus. The classical karyopherin receptor complex, such as the complex that uses Importin-β1 (encoded by gene KPNB1), is a heterodimer of an alpha subunit which recognizes the nuclear localization signal and a beta subunit which docks the complex at nucleoporins. However, Transportin-1 can directly bind to the cargo proteins and may not need importin alpha subunit to do it.<ref>R.A. Fridell (1997). ''Nuclear import of hnRNP A1 is mediated by a novel cellular cofactor related to karyopherin-beta''. Journal of Cell Science 1997 110: 1325-1331;</ref>

Transportin-1 is thought to use the same principal mechanism to carry out nuclear transport as other Importins. It mediates docking to the nuclear pore complex through binding to nucleoporin and is subsequently translocated through the pore by an energy requiring mechanism. Then, in the nucleus Ran binds to Transportin-1, it dissociates from cargo, and Transportin-1 is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. Then Transportin-1 is free to bind new cargo.

In addition, Transportin-1 is implicated in helping protein transport into primary cilium.<ref>Toby W. Hurd (2011). ''Localization of retinitis pigmentosa 2 to cilia is regulated by Importin β2''. J Cell Sci 2011 124: 718-726; doi: 10.1242/jcs.070839</ref> The function of Transportin-1 in this case is thought to be similar to carrying proteins into the nucleus through a nuclear pore. Transportin-1 binds cargo and then is helping this cargo to pass through a pore at the base of the cilium. Ran and nucleoporins are also implicated in this mechanism.<ref>Kee HL (2012). ''A size-exclusion permeability barrier and nucleoporins characterize a ciliary pore complex that regulates transport into cilia.''. Nat. Cell Biol. 2012 Mar 4;14(4):431-7. doi: 10.1038/ncb2450.</ref>

Alternate splicing of this gene results in two transcript variants encoding different proteins.<ref name="entrez" />

== Targets == Transportin 1 (TRN1) is part of the non-classical nuclear import pathway. In conjunction with the RanGTP hydrolysis 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.<ref name="pmid20606625">{{cite journal | vauthors = Dormann D, Rodde R, Edbauer D, Bentmann E, Fischer I, Hruscha A, Than ME, Mackenzie IR, Capell A, Schmid B, Neumann M, Haass C | title = ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import | journal = EMBO J. | volume = 29 | issue = 16 | pages = 2841–57 | date = August 2010 | pmid = 20606625 | pmc = 2924641 | doi = 10.1038/emboj.2010.143 }}</ref>

The type of cargo proteins that Transportin 1 can carry into the nucleus include RNA-binding proteins (such as hnRNP A1 and hnRNP F) and also ribosomal proteins.<ref>Anne-Christine Ström (2001). ''Importin-beta-like nuclear transport receptors''. Genome Biol. 2001; 2(6): reviews3008.1–reviews3008.9.</ref>

== Clinical significance == TRN1 has been implicated in the pathogenesis of two neurodegenerative diseases namely amyotrophic lateral sclerosis and frontotemporal dementia.<ref name="pmid21847626">{{cite journal|author5-link=Martin Rossor| vauthors = Brelstaff J, Lashley T, Holton JL, Lees AJ, Rossor MN, Bandopadhyay R, Revesz T | title = Transportin1: a marker of FTLD-FUS | journal = Acta Neuropathol. | volume = 122 | issue = 5 | pages = 591–600 | date = November 2011 | pmid = 21847626 | doi = 10.1007/s00401-011-0863-6 | s2cid = 5913873 }}</ref>

== Interactions == Transportin 1 has been shown to interact with: * RGPD5<ref name="pmid12905863">{{cite journal | vauthors = Cai Y, Miao SY, Wang LF | title = [Determination of the binding site of testis-specific nucleoporin BS-63 to transportin (karopherin beta 2) and the proof of their combination in vitro] | language = zh | journal = Zhongguo Yi Xue Ke Xue Yuan Xue Bao | volume = 23 | issue = 5 | pages = 462–6 | date = October 2001 | pmid = 12905863 }}</ref> and * Ran (biology).<ref name="pmid10353245">{{cite journal | vauthors = Chook YM, Blobel G | title = Structure of the nuclear transport complex karyopherin-beta2-Ran x GppNHp | journal = Nature | volume = 399 | issue = 6733 | pages = 230–7 | date = May 1999 | pmid = 10353245 | doi = 10.1038/20375 | bibcode = 1999Natur.399..230C | s2cid = 4413233 }}</ref><ref name="pmid12384575">{{cite journal | vauthors = Shamsher MK, Ploski J, Radu A | title = Karyopherin beta 2B participates in mRNA export from the nucleus | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 22 | pages = 14195–9 | date = October 2002 | pmid = 12384575 | pmc = 137860 | doi = 10.1073/pnas.212518199 | bibcode = 2002PNAS...9914195S | doi-access = free }}</ref>

== References == {{reflist}}

== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Bukrinsky MI, Haffar OK | title = HIV-1 nuclear import: in search of a leader | journal = Front. Biosci. | volume = 2 | issue = 4| pages = d578-87 | year = 1997 | pmid = 9366553 | doi = 10.2741/A213| doi-access = free }} * {{cite journal | vauthors = Bukrinsky MI, Haffar OK | title = HIV-1 nuclear import: matrix protein is back on center stage, this time together with Vpr | journal = Mol. Med. | volume = 4 | issue = 3 | pages = 138–43 | year = 1998 | pmid = 9562972 | pmc = 2230352 | doi = 10.1007/BF03401911}} * {{cite journal | vauthors = Bukrinsky MI, Sharova N, Dempsey MP, Stanwick TL, Bukrinskaya AG, Haggerty S, Stevenson M | title = Active nuclear import of human immunodeficiency virus type 1 preintegration complexes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 89 | issue = 14 | pages = 6580–4 | year = 1992 | pmid = 1631159 | pmc = 49545 | doi = 10.1073/pnas.89.14.6580 | bibcode = 1992PNAS...89.6580B | doi-access = free }} * {{cite journal | vauthors = Moroianu J, Hijikata M, Blobel G, Radu A | title = 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 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 92 | issue = 14 | pages = 6532–6 | year = 1995 | pmid = 7604027 | pmc = 41552 | doi = 10.1073/pnas.92.14.6532 | bibcode = 1995PNAS...92.6532M | doi-access = free }} * {{cite journal | vauthors = Bukrinsky MI, Haggerty S, Dempsey MP, Sharova N, Adzhubel A, Spitz L, Lewis P, Goldfarb D, Emerman M, Stevenson M | title = A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells | journal = Nature | volume = 365 | issue = 6447 | pages = 666–9 | year = 1993 | pmid = 8105392 | doi = 10.1038/365666a0 | pmc = 9524217 | bibcode = 1993Natur.365..666B | s2cid = 25678 }} * {{cite journal | vauthors = Michael WM, Choi M, Dreyfuss G | title = A nuclear export signal in hnRNP A1: a signal-mediated, temperature-dependent nuclear protein export pathway | journal = Cell | volume = 83 | issue = 3 | pages = 415–22 | year = 1995 | pmid = 8521471 | doi = 10.1016/0092-8674(95)90119-1 | s2cid = 615927 | doi-access = free }} * {{cite journal | vauthors = Nakielny S, Siomi MC, Siomi H, Michael WM, Pollard V, Dreyfuss G | title = Transportin: nuclear transport receptor of a novel nuclear protein import pathway | journal = Exp. Cell Res. | volume = 229 | issue = 2 | pages = 261–6 | year = 1996 | pmid = 8986607 | doi = 10.1006/excr.1996.0369 | doi-access = free }} * {{cite journal | vauthors = Fridell RA, Truant R, Thorne L, Benson RE, Cullen BR | title = Nuclear import of hnRNP A1 is mediated by a novel cellular cofactor related to karyopherin-beta | journal = J. Cell Sci. | volume = 110 | issue = 11 | pages = 1325–31 | year = 1997 | doi = 10.1242/jcs.110.11.1325 | pmid = 9202393 }} * {{cite journal | vauthors = Gallay P, Hope T, Chin D, Trono D | title = HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 18 | pages = 9825–30 | year = 1997 | pmid = 9275210 | pmc = 23276 | doi = 10.1073/pnas.94.18.9825 | bibcode = 1997PNAS...94.9825G | doi-access = free }} * {{cite journal | vauthors = Siomi MC, Eder PS, Kataoka N, Wan L, Liu Q, Dreyfuss G | title = Transportin-mediated nuclear import of heterogeneous nuclear RNP proteins | journal = J. Cell Biol. | volume = 138 | issue = 6 | pages = 1181–92 | year = 1997 | pmid = 9298975 | pmc = 2132560 | doi = 10.1083/jcb.138.6.1181 }} * {{cite journal | vauthors = Henderson BR, Percipalle P | title = Interactions between HIV Rev and nuclear import and export factors: the Rev nuclear localisation signal mediates specific binding to human importin-beta | journal = J. Mol. Biol. | volume = 274 | issue = 5 | pages = 693–707 | year = 1997 | pmid = 9405152 | doi = 10.1006/jmbi.1997.1420 }} * {{cite journal | vauthors = Efthymiadis A, Briggs LJ, Jans DA | title = The HIV-1 Tat nuclear localization sequence confers novel nuclear import properties | journal = J. Biol. Chem. | volume = 273 | issue = 3 | pages = 1623–8 | year = 1998 | pmid = 9430704 | doi = 10.1074/jbc.273.3.1623 | doi-access = free }} * {{cite journal | vauthors = Vodicka MA, Koepp DM, Silver PA, Emerman M | title = HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection | journal = Genes Dev. | volume = 12 | issue = 2 | pages = 175–85 | year = 1998 | pmid = 9436978 | pmc = 316441 | doi = 10.1101/gad.12.2.175 }} * {{cite journal | vauthors = Popov S, Rexach M, Zybarth G, Reiling N, Lee MA, Ratner L, Lane CM, Moore MS, Blobel G, Bukrinsky M | title = Viral protein R regulates nuclear import of the HIV-1 pre-integration complex | journal = EMBO J. | volume = 17 | issue = 4 | pages = 909–17 | year = 1998 | pmid = 9463369 | pmc = 1170440 | doi = 10.1093/emboj/17.4.909 }} * {{cite journal | vauthors = Popov S, Rexach M, Ratner L, Blobel G, Bukrinsky M | title = Viral protein R regulates docking of the HIV-1 preintegration complex to the nuclear pore complex | journal = J. Biol. Chem. | volume = 273 | issue = 21 | pages = 13347–52 | year = 1998 | pmid = 9582382 | doi = 10.1074/jbc.273.21.13347 | doi-access = free }} * {{cite journal | vauthors = Fouchier RA, Meyer BE, Simon JH, Fischer U, Albright AV, González-Scarano F, Malim MH | title = Interaction of the human immunodeficiency virus type 1 Vpr protein with the nuclear pore complex | journal = J. Virol. | volume = 72 | issue = 7 | pages = 6004–13 | year = 1998 | pmid = 9621063 | pmc = 110405 | doi = 10.1128/JVI.72.7.6004-6013.1998}} {{refend}}