Transportin 1

TNPO1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1QBK, 2H4M, 2OT8, 2QMR, 2Z5J, 2Z5K, 2Z5M, 2Z5N, 2Z5O, 4FDD, 4FQ3, 4JLQ, 4OO6 Contents Function ; Targets ; Clinical significance ; Interactions ; References ; Further reading ;
Identifiers
Aliases	TNPO1 , IPO2, KPNB2, MIP, MIP1, TRN, Transportin 1
External IDs	OMIM: 602901 MGI: 2681523 HomoloGene: 5358 GeneCards: TNPO1
Gene location (Human)
Chr.	Chromosome 5 (human)
End	72,916,733 bp
Gene location (Mouse)
Chr.	Chromosome 13 (mouse)
End	99,062,892 bp
RNA expression pattern
	Top expressed in
	corpus epididymis; ; caput epididymis; ; pylorus; ; secondary oocyte; ; optic nerve; ; cardia; ; renal medulla; ; pericardium; ; nipple; ; visceral pleura;
	Top expressed in
	pineal gland; ; secondary oocyte; ; cumulus cell; ; abdominal wall; ; retina; ; primitive streak; ; left lung lobe; ; maxillary prominence; ; spermatid; ; atrium;
	More reference expression data
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	protein binding ; nuclear localization sequence binding ; RNA binding ;
Cellular component	cytoplasm ; cytosol ; nuclear membrane ; nuclear periphery ; extracellular exosome ; nucleus ; cilium ;
Biological process	ribosomal protein import into nucleus ; regulation of mRNA stability ; protein transport ; viral process ; intracellular protein transport ; NLS-bearing protein import into nucleus ; intraciliary transport involved in cilium assembly ; transport ; protein import into nucleus ;
	Sources:Amigo / QuickGO
Orthologs
	3842
	238799
	ENSG00000083312
	ENSMUSG00000009470
	Q92973
	Q8BFY9
	NM_002270 ; NM_153188
	NM_001048267 ; NM_178716
NP_002261 ; NP_694858 ; NP_001351221 ; NP_001351222 ; NP_001351223 ;
	NP_001351224 ; NP_001351225
	NP_001041732 ; NP_848831
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated December 24, 2023

Transportin-1 (or Importin-β2) is a protein that in humans is encoded by the TNPO1 gene.^[5]^[6]^[7]

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.^[8]

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.^[9] 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.^[10]

Alternate splicing of this gene results in two transcript variants encoding different proteins.^[7]

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.^[11]

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.^[12]

Clinical significance

TRN1 has been implicated in the pathogenesis of two neurodegenerative diseases namely amyotrophic lateral sclerosis and frontotemporal dementia.^[13]

Interactions

Transportin 1 has been shown to interact with:

RGPD5 ^[14] and
Ran (biology).^[15]^[16]

Related Research Articles

A nuclear pore is a channel as part of the nuclear pore complex (NPC), a large protein complex found in the nuclear envelope in eukaryotic cells, enveloping the cell nucleus containing DNA, which facilitates the selective membrane transport of various molecules across the membrane.

A nuclear localization signalorsequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines or arginines exposed on the protein surface. Different nuclear localized proteins may share the same NLS. An NLS has the opposite function of a nuclear export signal (NES), which targets proteins out of the nucleus.

Importin is a type of karyopherin that transports protein molecules from the cell's cytoplasm to the nucleus. It does so by binding to specific recognition sequences, called nuclear localization sequences (NLS).

Ran also known as GTP-binding nuclear protein Ran is a protein that in humans is encoded by the RAN gene. Ran is a small 25 kDa protein that is involved in transport into and out of the cell nucleus during interphase and also involved in mitosis. It is a member of the Ras superfamily.

Nuclear pore glycoprotein p62 is a protein complex associated with the nuclear envelope. The p62 protein remains associated with the nuclear pore complex-lamina fraction. p62 is synthesized as a soluble cytoplasmic precursor of 61 kDa followed by modification that involve addition of N-acetylglucosamine residues, followed by association with other complex proteins. In humans it is encoded by the NUP62 gene.

Nucleoporins are a family of proteins which are the constituent building blocks of the nuclear pore complex (NPC). The nuclear pore complex is a massive structure embedded in the nuclear envelope at sites where the inner and outer nuclear membranes fuse, forming a gateway that regulates the flow of macromolecules between the cell nucleus and the cytoplasm. Nuclear pores enable the passive and facilitated transport of molecules across the nuclear envelope. Nucleoporins, a family of around 30 proteins, are the main components of the nuclear pore complex in eukaryotic cells. Nucleoporin 62 is the most abundant member of this family. Nucleoporins are able to transport molecules across the nuclear envelope at a very high rate. A single NPC is able to transport 60,000 protein molecules across the nuclear envelope every minute.

Importin subunit alpha-1 is a protein that in humans is encoded by the KPNA2 gene.

Importin subunit beta-1 is a protein that in humans is encoded by the KPNB1 gene.

Importin subunit alpha-5 is a protein that in humans is encoded by the KPNA1 gene.

Heterogeneous nuclear ribonucleoprotein A1 is a protein that in humans is encoded by the HNRNPA1 gene. Mutations in hnRNP A1 are causative of amyotrophic lateral sclerosis and the syndrome multisystem proteinopathy.

Nuclear pore complex protein Nup98-Nup96 is a protein that in humans is encoded by the NUP98 gene.

Importin subunit alpha-4 also known as karyopherin subunit alpha-3 is a protein that in humans is encoded by the KPNA3 gene.

Importin subunit alpha-7 is a protein that in humans is encoded by the KPNA6 gene.

Importin subunit alpha-3, also known as karyopherin subunit alpha-4, is a protein that in humans is encoded by the KPNA4 gene.

<span class="mw-page-title-main">IPO5</span> Protein-coding gene in the species Homo sapiens

Importin-5 is a protein that in humans is encoded by the IPO5 gene. The protein encoded by this gene is a member of the importin beta family. Structurally, the protein adopts the shape of a right hand solenoid and is composed of 24 HEAT repeats.

Importin subunit alpha-6 is a protein that in humans is encoded by the KPNA5 gene.

Nucleoporin 153 (Nup153) is a protein which in humans is encoded by the NUP153 gene. It is an essential component of the basket of nuclear pore complexes (NPCs) in vertebrates, and required for the anchoring of NPCs. It also acts as the docking site of an importing karyopherin. On the cytoplasmic side of the NPC, Nup358 fulfills an analogous role.

Nucleoporin 50 (Nup50) is a protein that in humans is encoded by the NUP50 gene.

Importin-7 is a protein that in humans is encoded by the IPO7 gene.

Transportin-2 is a protein that in humans is encoded by the TNPO2 gene.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000083312 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000009470 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ 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. S2CID 15666255.
↑ 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. Bibcode:1997PNAS...94.5055B. doi: 10.1073/pnas.94.10.5055 . PMC 24630 . PMID 9144189.
1 2 "Entrez Gene: TNPO1 transportin 1".
↑ 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;
↑ 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
↑ 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.
↑ 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.
↑ Anne-Christine Ström (2001). Importin-beta-like nuclear transport receptors. Genome Biol. 2001; 2(6): reviews3008.1–reviews3008.9.
↑ 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. S2CID 5913873.
↑ 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. Bibcode:1999Natur.399..230C. doi:10.1038/20375. PMID 10353245. S2CID 4413233.
↑ 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. Bibcode:2002PNAS...9914195S. doi: 10.1073/pnas.212518199 . PMC 137860 . PMID 12384575.

Bukrinsky MI, Haffar OK (1997). "HIV-1 nuclear import: in search of a leader". Front. Biosci. 2 (4): d578-87. doi: 10.2741/A213 . 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. doi:10.1007/BF03401911. PMC 2230352 . PMID 9562972.
Bukrinsky MI, Sharova N, Dempsey MP, Stanwick TL, Bukrinskaya AG, Haggerty S, Stevenson M (1992). "Active nuclear import of human immunodeficiency virus type 1 preintegration complexes". Proc. Natl. Acad. Sci. U.S.A. 89 (14): 6580–4. Bibcode:1992PNAS...89.6580B. 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. Bibcode:1995PNAS...92.6532M. doi: 10.1073/pnas.92.14.6532 . PMC 41552 . PMID 7604027.
Bukrinsky MI, Haggerty S, Dempsey MP, Sharova N, Adzhubel A, Spitz L, Lewis P, Goldfarb D, Emerman M, Stevenson M (1993). "A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells". Nature. 365 (6447): 666–9. Bibcode:1993Natur.365..666B. doi:10.1038/365666a0. PMC 9524217 . PMID 8105392. S2CID 25678.
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. S2CID 615927.
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 (11): 1325–31. doi:10.1242/jcs.110.11.1325. 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. Bibcode:1997PNAS...94.9825G. 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, Lane CM, Moore MS, Blobel G, Bukrinsky M (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, Malim MH (1998). "Interaction of the human immunodeficiency virus type 1 Vpr protein with the nuclear pore complex". J. Virol. 72 (7): 6004–13. doi:10.1128/JVI.72.7.6004-6013.1998. PMC 110405 . PMID 9621063.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000083312 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000009470 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8808633-5] 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. S2CID 15666255.

[pmid9144189-6] 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. Bibcode:1997PNAS...94.5055B. doi: 10.1073/pnas.94.10.5055 . PMC 24630 . PMID 9144189.

[entrez-7] 1 2 "Entrez Gene: TNPO1 transportin 1".

[8] 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;

[9] 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

[10] 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.

[pmid20606625-11] 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.

[12] Anne-Christine Ström (2001). Importin-beta-like nuclear transport receptors. Genome Biol. 2001; 2(6): reviews3008.1–reviews3008.9.

[pmid21847626-13] 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. S2CID 5913873.

[pmid12905863-14] 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.

[pmid10353245-15] Chook YM, Blobel G (May 1999). "Structure of the nuclear transport complex karyopherin-beta2-Ran x GppNHp". Nature. 399 (6733): 230–7. Bibcode:1999Natur.399..230C. doi:10.1038/20375. PMID 10353245. S2CID 4413233.

[pmid12384575-16] 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. Bibcode:2002PNAS...9914195S. doi: 10.1073/pnas.212518199 . PMC 137860 . PMID 12384575.

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