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Gene Review

TNPO1  -  transportin 1

Homo sapiens

Synonyms: IPO2, Importin beta-2, KPNB2, Karyopherin beta-2, M9 region interaction protein, ...
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Disease relevance of TNPO1

  • Surprisingly, nuclear export of several substrates including importin-alpha and -beta, transportin, HIV Rev and tRNA appears to require nuclear RanGTP but may not require GTP hydrolysis by Ran, suggesting that the energy for their nuclear export is supplied by another source [1].
  • We have identified a major gamma-herpesvirus-divergent locus (DL-B) in HHV-8 DNA encoding several HHV-8 unique open reading frames (ORFs), including a homologue of interleukin-6 (IL-6) and two homologues of macrophage inflammatory protein MIP-1 [2].
  • Of interest, IFN-DCs exhibited a marked chemotactic response to MIP-3beta in vitro and strong migratory behavior in severe combined immunodeficient (SCID) mice [3].
  • A monoclonal antibody to a cell surface glycoprotein on human colorectal carcinomas was raised using the undifferentiated colon carcinoma cell line MIP 101 as the immunogen [4].
  • Thus, in addition to MIP-1 and -2 other not yet defined chemotactic factors are of importance for recruitment of leukocytes in bacterial meningitis [5].

Psychiatry related information on TNPO1

  • We devised a method that permits accurate measurement of MIP, with near maximal values, and does not require patient cooperation [6].
  • Although both groups scored high on the Mania Rating Scale, MIP patients had significantly more often been diagnosed as schizophrenic, or anxiety disorders, with long delays to first diagnosis as bipolar disorder [7].

High impact information on TNPO1

  • SIN1/MIP1 Maintains rictor-mTOR Complex Integrity and Regulates Akt Phosphorylation and Substrate Specificity [8].
  • Transportin is a 90 kDa protein, distantly related to importin beta, and we show that it mediates the nuclear import of M9-containing proteins [9].
  • Ran x GppNHp in the complex shows extensive structural rearrangement, compared to Ran GDP, in regions contacting karyopherin-beta2 [10].
  • MIP-1 proteins may enhance these effects through the chemotactic recruitment of endogenous cytokine-producing cells into affected tissues and could potentially influence HIV disease progression in coinfected individuals through interactions with the HIV co-receptor CCR-5 [2].
  • However, in contrast to these two endogenous pyrogens, the fever induced by MIP-1 was not inhibited by the cyclooxygenase inhibitor ibuprofen [11].

Chemical compound and disease context of TNPO1


Biological context of TNPO1


Anatomical context of TNPO1

  • RanBP7 binds directly to nuclear pore complexes where it competes for binding sites with importin-beta, transportin, and apparently also with the mediators of mRNA and U snRNA export [22].
  • Furthermore, c-Fos mutants that interact with transportin but not with importin beta were efficiently imported in the presence of cytosol [23].
  • Induction depended on productive viral infection: not only did the kinetics of MIP-1 peptide induction closely follow those of viral replication, but monocyte cultures inoculated with heat-inactivated virus or infected in the presence of AZT failed to produce these chemokine beta peptides [24].
  • The suppressive effects of natural MIP-1 and rMIP-1 alpha were also apparent on a population of BFU-E, CFU-GEMM, and CFU-GM present in cell-sorted fractions of human bone marrow (CD34 HLA-DR+) highly enriched for progenitors with cloning efficiencies of 42% to 75% [25].
  • In particular, the non-invasive SNP is more sensitive than VC and MIP, suggesting that it could usefully be included in tests of respiratory muscle strength in ALS and will be helpful in assessing the risk of ventilatory failure [26].

Associations of TNPO1 with chemical compounds

  • Thus, MIP-1 may participate in the febrile response that is not mediated through prostaglandin synthesis and clinically cannot be ablated by cyclooxygenase inhibitors [11].
  • However, progressive increase of immunogenicity occurred in leukemic cells in the course of in vitro treatments with DTIC plus MIP, but not with MLP alone, as evidenced by comparative studies on transplantation immunity elicited in BALB/c x DBA/2 F1 mice by graded inocula of L1210D or L1210N leukemia cells [27].
  • With the objective of optimizing a polymer imprinted with the local anaesthetic Bupivacaine for use in pure aqueous systems, a polymer library was prepared by varying the original poly(MAA-co-EDMA) MIP composition [28].
  • As hypothesized, inositol reduction resulted from decreased MIP synthase activity: .21-.28 mmol/LVPA reduced the activity by 50% [29].
  • CONCLUSIONS: The rate-limiting step of inositol biosynthesis, catalyzed by MIP synthase, is inhibited by VPA; inositol depletion is a first event shown to be common to lithium and VPA [29].

Physical interactions of TNPO1


Other interactions of TNPO1

  • The nucleoporin Nup98 is a site for GDP/GTP exchange on ran and termination of karyopherin beta 2-mediated nuclear import [30].
  • Signal recognition particle protein 19 is imported into the nucleus by importin 8 (RanBP8) and transportin [31].
  • Although transportin is known to import a variety of proteins, SRP19 import is the first function assigned to importin 8 [31].
  • Here we have investigated the subfamily of transportins that consists of Trn1 (or Kap beta2A) and two alternatively spliced Trn2 isoforms (Trn2a and Trn2b), also called Trn2 and Kap beta2B [32].
  • Consistent with the solution binding results, karyopherin beta2 inhibited karyopherin alpha/beta1-mediated import of a classical NLS containing substrate and, vice versa, beta1 inhibited beta2-mediated import of A1 substrate, suggesting that the two import pathways merge at the level of docking of beta1 and beta2 to repeat nucleoporins [17].

Analytical, diagnostic and therapeutic context of TNPO1

  • Cytoplasmic microinjection of a truncated form of MIP that retains the M9 binding site blocked the in vivo nuclear import of a substrate containing the M9 NLS yet failed to affect the import of a similar substrate bearing a basic NLS [33].
  • Using ST immunohistochemistry, MIP-1 alpha+ cells from RA compared with normal were predominantly m phi s and lining cells (P < 0.05) [34].
  • Sensitized cells were also examined for their ability to respond to purified protein derivative (PPD) by blastogenesis, migration inhibitory factor release (MIP), and lymphotoxin (LT) production, both before and after treatment with HTLA and complement [35].
  • Using a biotinylated chemokine binding assay with confocal microscopy and three-dimensional image reconstruction, spatially resolved binding sites for MCP-1 and MIP-alpha around human brain microvessels were revealed for the first time [36].
  • Is the tolerance to MIP chemotherapy different between English and other European populations [37]?


  1. The asymmetric distribution of the constituents of the Ran system is essential for transport into and out of the nucleus. Izaurralde, E., Kutay, U., von Kobbe, C., Mattaj, I.W., Görlich, D. EMBO J. (1997) [Pubmed]
  2. Kaposi's sarcoma-associated human herpesvirus-8 encodes homologues of macrophage inflammatory protein-1 and interleukin-6. Nicholas, J., Ruvolo, V.R., Burns, W.H., Sandford, G., Wan, X., Ciufo, D., Hendrickson, S.B., Guo, H.G., Hayward, G.S., Reitz, M.S. Nat. Med. (1997) [Pubmed]
  3. Expression of CCR-7, MIP-3beta, and Th-1 chemokines in type I IFN-induced monocyte-derived dendritic cells: importance for the rapid acquisition of potent migratory and functional activities. Parlato, S., Santini, S.M., Lapenta, C., Di Pucchio, T., Logozzi, M., Spada, M., Giammarioli, A.M., Malorni, W., Fais, S., Belardelli, F. Blood (2001) [Pubmed]
  4. A cell surface glycoprotein expressed by colorectal carcinomas including poorly differentiated, noncarcinoembryonic antigen-producing colorectal tumors. Salem, R.R., Wolf, B.C., Sears, H.F., Thomas, P., Bollinger, B., Zamcheck, N., Saravis, C.A., Chen, L.B., Steele, G. Cancer Res. (1988) [Pubmed]
  5. Experimental Listeria meningoencephalitis. Macrophage inflammatory protein-1 alpha and -2 are produced intrathecally and mediate chemotactic activity in cerebrospinal fluid of infected mice. Seebach, J., Bartholdi, D., Frei, K., Spanaus, K.S., Ferrero, E., Widmer, U., Isenmann, S., Strieter, R.M., Schwab, M., Pfister, H., Fontana, A. J. Immunol. (1995) [Pubmed]
  6. Validation of a technique to assess maximal inspiratory pressure in poorly cooperative patients. Truwit, J.D., Marini, J.J. Chest (1992) [Pubmed]
  7. The mood-instability hypothesis in the origin of mood-congruent versus mood-incongruent psychotic distinction in mania: validation in a French National Study of 1090 patients. Azorin, J.M., Akiskal, H., Hantouche, E. Journal of affective disorders (2006) [Pubmed]
  8. SIN1/MIP1 Maintains rictor-mTOR Complex Integrity and Regulates Akt Phosphorylation and Substrate Specificity. Jacinto, E., Facchinetti, V., Liu, D., Soto, N., Wei, S., Jung, S.Y., Huang, Q., Qin, J., Su, B. Cell (2006) [Pubmed]
  9. A novel receptor-mediated nuclear protein import pathway. Pollard, V.W., Michael, W.M., Nakielny, S., Siomi, M.C., Wang, F., Dreyfuss, G. Cell (1996) [Pubmed]
  10. Structure of the nuclear transport complex karyopherin-beta2-Ran x GppNHp. Chook, Y.M., Blobel, G. Nature (1999) [Pubmed]
  11. Macrophage inflammatory protein-1: a prostaglandin-independent endogenous pyrogen. Davatelis, G., Wolpe, S.D., Sherry, B., Dayer, J.M., Chicheportiche, R., Cerami, A. Science (1989) [Pubmed]
  12. Efficacy and toxicity of mitomycin, ifosfamide, and cisplatin (MIP) in patients with inoperable non-small cell lung cancer. Urban, T., Bedin, A., Baud, M., Chouaid, C., Febvre, M., Lebeau, B. Lung Cancer (1996) [Pubmed]
  13. Ventilatory muscle strength and endurance in myasthenia gravis. Keenan, S.P., Alexander, D., Road, J.D., Ryan, C.F., Oger, J., Wilcox, P.G. Eur. Respir. J. (1995) [Pubmed]
  14. Quality of life (QOL) assessment of MIP (mitomycin, ifosfamide and cisplatin) chemotherapy in advanced non-small cell lung cancers (NSCLC). Han, J.Y., Kim, H.K., Choi, B.G., Moon, H., Hong, Y.S., Lee, K.S. Jpn. J. Clin. Oncol. (1998) [Pubmed]
  15. Efficiency of CT-angiography in the diagnosis of intracranial aneurysms. Sasiadek, M., Kowalewski, K., Turek, T., Hendrich, B., Podkowa, J., Maksymowicz, H. Med. Sci. Monit. (2002) [Pubmed]
  16. Prognostic factors in multiple myeloma treated with prednisolone and sequential melphalan and ifosfamide: MIP combination chemotherapy. Adachi, T., Asano, K., Sezaki, T., Takahashi, I., Kimura, I. Acta Med. Okayama (1982) [Pubmed]
  17. Karyopherin beta2 mediates nuclear import of a mRNA binding protein. Bonifaci, N., Moroianu, J., Radu, A., Blobel, G. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  18. Importin beta, transportin, RanBP5 and RanBP7 mediate nuclear import of ribosomal proteins in mammalian cells. Jäkel, S., Görlich, D. EMBO J. (1998) [Pubmed]
  19. Transportin-mediated nuclear import of heterogeneous nuclear RNP proteins. Siomi, M.C., Eder, P.S., Kataoka, N., Wan, L., Liu, Q., Dreyfuss, G. J. Cell Biol. (1997) [Pubmed]
  20. Definition of a consensus transportin-specific nucleocytoplasmic transport signal. Bogerd, H.P., Benson, R.E., Truant, R., Herold, A., Phingbodhipakkiya, M., Cullen, B.R. J. Biol. Chem. (1999) [Pubmed]
  21. Myelopoietic enhancing effects of murine macrophage inflammatory proteins 1 and 2 on colony formation in vitro by murine and human bone marrow granulocyte/macrophage progenitor cells. Broxmeyer, H.E., Sherry, B., Lu, L., Cooper, S., Carow, C., Wolpe, S.D., Cerami, A. J. Exp. Med. (1989) [Pubmed]
  22. A novel class of RanGTP binding proteins. Görlich, D., Dabrowski, M., Bischoff, F.R., Kutay, U., Bork, P., Hartmann, E., Prehn, S., Izaurralde, E. J. Cell Biol. (1997) [Pubmed]
  23. Transportin is a major nuclear import receptor for c-Fos: a novel mode of cargo interaction. Arnold, M., Nath, A., Wohlwend, D., Kehlenbach, R.H. J. Biol. Chem. (2006) [Pubmed]
  24. Human immunodeficiency virus type 1 infection alters chemokine beta peptide expression in human monocytes: implications for recruitment of leukocytes into brain and lymph nodes. Schmidtmayerova, H., Nottet, H.S., Nuovo, G., Raabe, T., Flanagan, C.R., Dubrovsky, L., Gendelman, H.E., Cerami, A., Bukrinsky, M., Sherry, B. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  25. Enhancing and suppressing effects of recombinant murine macrophage inflammatory proteins on colony formation in vitro by bone marrow myeloid progenitor cells. Broxmeyer, H.E., Sherry, B., Lu, L., Cooper, S., Oh, K.O., Tekamp-Olson, P., Kwon, B.S., Cerami, A. Blood (1990) [Pubmed]
  26. Respiratory muscle strength and ventilatory failure in amyotrophic lateral sclerosis. Lyall, R.A., Donaldson, N., Polkey, M.I., Leigh, P.N., Moxham, J. Brain (2001) [Pubmed]
  27. In vitro generation of a highly immunogenic subline of L1210 leukemia following exposure to 5-(3,3'-dimethyl-1-triazeno)imidazole-4-carboxamide. Contessa, A.R., Bonmassar, A., Giampietri, A., Circolo, A., Goldin, A., Fioretti, M.C. Cancer Res. (1981) [Pubmed]
  28. Water-compatible molecularly imprinted polymers obtained via high-throughput synthesis and experimental design. Dirion, B., Cobb, Z., Schillinger, E., Andersson, L.I., Sellergren, B. J. Am. Chem. Soc. (2003) [Pubmed]
  29. Valproate decreases inositol biosynthesis. Shaltiel, G., Shamir, A., Shapiro, J., Ding, D., Dalton, E., Bialer, M., Harwood, A.J., Belmaker, R.H., Greenberg, M.L., Agam, G. Biol. Psychiatry (2004) [Pubmed]
  30. The nucleoporin Nup98 is a site for GDP/GTP exchange on ran and termination of karyopherin beta 2-mediated nuclear import. Fontoura, B.M., Blobel, G., Yaseen, N.R. J. Biol. Chem. (2000) [Pubmed]
  31. Signal recognition particle protein 19 is imported into the nucleus by importin 8 (RanBP8) and transportin. Dean, K.A., von Ahsen, O., Görlich, D., Fried, H.M. J. Cell. Sci. (2001) [Pubmed]
  32. Transportins 1 and 2 are redundant nuclear import factors for hnRNP A1 and HuR. Rebane, A., Aab, A., Steitz, J.A. RNA (2004) [Pubmed]
  33. Nuclear import of hnRNP A1 is mediated by a novel cellular cofactor related to karyopherin-beta. Fridell, R.A., Truant, R., Thorne, L., Benson, R.E., Cullen, B.R. J. Cell. Sci. (1997) [Pubmed]
  34. Macrophage inflammatory protein-1 alpha. A novel chemotactic cytokine for macrophages in rheumatoid arthritis. Koch, A.E., Kunkel, S.L., Harlow, L.A., Mazarakis, D.D., Haines, G.K., Burdick, M.D., Pope, R.M., Strieter, R.M. J. Clin. Invest. (1994) [Pubmed]
  35. Human T-cell heterogeneity as delineated with a specific human thymus lymphocyte antiserum. In vitro effects on mitogen response mixed leukocyte culture, cell-mediated lymphocytotoxicity, and lymphokine production. Woody, J.N., Ahmed, A., Knudsen, R.C., Strong, D.M., Sell, K.W. J. Clin. Invest. (1975) [Pubmed]
  36. Visualization of chemokine binding sites on human brain microvessels. Andjelkovic, A.V., Spencer, D.D., Pachter, J.S. J. Cell Biol. (1999) [Pubmed]
  37. Is the tolerance to MIP chemotherapy different between English and other European populations? Berghmans, T., Sculier, J.P. J. Clin. Oncol. (2005) [Pubmed]
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