Transportin 1

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TNPO1
Protein TNPO1 PDB 1qbk.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TNPO1, IPO2, KPNB2, MIP, MIP1, TRN, Transportin 1
External IDs MGI: 2681523 HomoloGene: 5358 GeneCards: TNPO1
RNA expression pattern
PBB GE TNPO1 207657 x at fs.png

PBB GE TNPO1 221829 s at fs.png

PBB GE TNPO1 209225 x at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002270
NM_153188

NM_001048267
NM_178716

RefSeq (protein)

NP_002261
NP_694858

NP_001041732.1
NP_848831.2
NP_001041732
NP_848831

Location (UCSC) Chr 5: 72.82 – 72.92 Mb Chr 13: 98.84 – 98.93 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Transportin-1 (or Importin-β 2) is a protein that in humans is encoded by the TNPO1 gene.[3][4][5]

Function[edit]

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.[6]

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.[7] 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.[8]

Alternate splicing of this gene results in two transcript variants encoding different proteins.[5]

Targets[edit]

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.[9]

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.[10]

Clinical Significance[edit]

TRN1 has been implicated in the pathogenesis of two neurodegenerative diseases namely Amyotrophic lateral sclerosis and frontotemporal dementia.[11]

Interactions[edit]

Transportin 1 has been shown to interact with:

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ 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. 
  4. ^ 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 24630Freely accessible. PMID 9144189. 
  5. ^ a b "Entrez Gene: TNPO1 transportin 1". 
  6. ^ 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;
  7. ^ 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
  8. ^ 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.
  9. ^ 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 2924641Freely accessible. PMID 20606625. 
  10. ^ Anne-Christine Ström (2001). Importin-beta-like nuclear transport receptors. Genome Biol. 2001; 2(6): reviews3008.1–reviews3008.9.
  11. ^ 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. 
  12. ^ 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. 
  13. ^ 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. 
  14. ^ 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 137860Freely accessible. PMID 12384575. 

Further reading[edit]