Transportin 1: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''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 | pmc =  | doi = 10.1016/S0092-8674(00)80173-7 }}</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 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TNPO1 transportin 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3842| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
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>
| image = PBB_Protein_TNPO1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1qbk.
| PDB = {{PDB2|1qbk}}, {{PDB2|2h4m}}, {{PDB2|2ot8}}
| Name = Transportin 1
| HGNCid = 6401
| Symbol = TNPO1
| AltSymbols =; IPO2; KPNB2; MIP; MIP1; TRN
| OMIM = 602901
| ECnumber = 
| Homologene = 5358
| MGIid = 2681523
| GeneAtlas_image1 = PBB_GE_TNPO1_221829_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_TNPO1_207657_x_at_tn.png
| GeneAtlas_image3 = PBB_GE_TNPO1_209225_x_at_tn.png
| Function = {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0008139 |text = nuclear localization sequence binding}} {{GNF_GO|id=GO:0008565 |text = protein transporter activity}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005643 |text = nuclear pore}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}}
| Process = {{GNF_GO|id=GO:0000059 |text = protein import into nucleus, docking}} {{GNF_GO|id=GO:0000060 |text = protein import into nucleus, translocation}} {{GNF_GO|id=GO:0006886 |text = intracellular protein transport}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 3842
    | Hs_Ensembl = ENSG00000083312
    | Hs_RefseqProtein = NP_002261
    | Hs_RefseqmRNA = NM_002270
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 5
    | Hs_GenLoc_start = 72148171
    | Hs_GenLoc_end = 72248316
    | Hs_Uniprot = Q92973
    | Mm_EntrezGene = 238799
    | Mm_Ensembl = ENSMUSG00000009470
    | Mm_RefseqmRNA = NM_001048267
    | Mm_RefseqProtein = NP_001041732
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 13
    | Mm_GenLoc_start = 99942895
    | Mm_GenLoc_end = 100026541
    | Mm_Uniprot = Q3TKD0
  }}
}}
'''Transportin 1''', also known as '''TNPO1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: TNPO1 transportin 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3842| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
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.
{{PBB_Summary
| section_title =
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: TNPO1 transportin 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3842| accessdate = }}</ref>
}}


==References==
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>
{{reflist|2}}
 
==Further reading==
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]] 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]].<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 | 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 }}</ref>
 
== Interactions ==
Transportin 1 has been shown to [[Protein-protein interaction|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 = Chinese | journal = Zhongguo Yi Xue Ke Xue Yuan Xue Bao | volume = 23 | issue = 5 | pages = 462–6  | date = October 2001 | pmid = 12905863 | doi =  }}</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 }}</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 }}</ref>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Bukrinsky MI, Haffar OK | title = HIV-1 nuclear import: in search of a leader | journal = Front. Biosci. | volume = 2 | issue =  | pages = d578-87 | year = 1997 | pmid = 9366553 | doi =  10.2741/A213}}
| citations =
* {{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 =  }}
*{{cite journal | author=Bukrinsky MI, Haffar OK |title=HIV-1 nuclear import: in search of a leader. |journal=Front. Biosci. |volume=2 |issue=  |pages= d578-87 |year= 2004 |pmid= 9366553 |doi=  }}
* {{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 }}
*{{cite journal | author=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 |doi=  }}
* {{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 }}
*{{cite journal | author=Bukrinsky MI, Sharova N, Dempsey MP, ''et al.'' |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 |doi= }}
* {{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 }}
*{{cite journal | author=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 |doi= }}
* {{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 }}
*{{cite journal | author=Bukrinsky MI, Haggerty S, Dempsey MP, ''et al.'' |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 }}
* {{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 }}
*{{cite journal | author=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= 1996 |pmid= 8521471 |doi= }}
* {{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 | pmid = 9202393 | doi =  }}
*{{cite journal  | author=Pollard VW, Michael WM, Nakielny S, ''et al.'' |title=A novel receptor-mediated nuclear protein import pathway. |journal=Cell |volume=86 |issue= 6 |pages= 985-94 |year= 1996 |pmid= 8808633 |doi=  }}
* {{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 }}
*{{cite journal | author=Nakielny S, Siomi MC, Siomi H, ''et al.'' |title=Transportin: nuclear transport receptor of a novel nuclear protein import pathway. |journal=Exp. Cell Res. |volume=229 |issue= 2 |pages= 261-6 |year= 1997 |pmid= 8986607 |doi= 10.1006/excr.1996.0369 }}
* {{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 | author=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 |year= 1997 |pmid= 9144189 |doi=  }}
* {{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  | author=Fridell RA, Truant R, Thorne L, ''et al.'' |title=Nuclear import of hnRNP A1 is mediated by a novel cellular cofactor related to karyopherin-beta. |journal=J. Cell. Sci. |volume=110 ( Pt 11) |issue= |pages= 1325-31 |year= 1997 |pmid= 9202393 |doi=  }}
* {{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 }}
*{{cite journal | author=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 |doi= }}
* {{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 | author=Siomi MC, Eder PS, Kataoka N, ''et al.'' |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 |doi= }}
* {{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 | author=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= 1998 |pmid= 9405152 |doi= 10.1006/jmbi.1997.1420 }}
* {{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 }}
*{{cite journal | author=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= }}
* {{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 =  }}
*{{cite journal | author=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 |doi= }}
*{{cite journal | author=Popov S, Rexach M, Zybarth G, ''et al.'' |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 |doi= 10.1093/emboj/17.4.909 }}
*{{cite journal | author=Popov S, Rexach M, Ratner L, ''et al.'' |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= }}
*{{cite journal | author=Fouchier RA, Meyer BE, Simon JH, ''et al.'' |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 |doi=  }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
{{PDB Gallery|geneid=3842}}

Latest revision as of 02:30, 11 November 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
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View/Edit Human

Transportin-1 (or Importin-β 2) is a protein that in humans is encoded by the TNPO1 gene.[1][2][3]

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.[4]

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.[5] 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.[6]

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.[7]

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.[8]

Clinical Significance

TRN1 has been implicated in the pathogenesis of two neurodegenerative diseases namely Amyotrophic lateral sclerosis and frontotemporal dementia.[9]

Interactions

Transportin 1 has been shown to interact with:

References

  1. ↑ 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.
  2. ↑ 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. ↑ 3.0 3.1 "Entrez Gene: TNPO1 transportin 1".
  4. ↑ 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;
  5. ↑ 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
  6. ↑ 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.
  7. ↑ Dormann D, Rodde R, Edbauer D, Bentmann E, Fischer I, Hruscha A, Than ME, Mackenzie IR, Capell A, Schmid B, Neumann M, Haass C (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.
  8. ↑ Anne-Christine Ström (2001). Importin-beta-like nuclear transport receptors. Genome Biol. 2001; 2(6): reviews3008.1–reviews3008.9.
  9. ↑ Brelstaff J, Lashley T, Holton JL, Lees AJ, Rossor MN, Bandopadhyay R, Revesz T (November 2011). "Transportin1: a marker of FTLD-FUS". Acta Neuropathol. 122 (5): 591–600. doi:10.1007/s00401-011-0863-6. PMID 21847626.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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

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