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Gene Review

LMO2  -  LIM domain only 2 (rhombotin-like 1)

Homo sapiens

Synonyms: Cysteine-rich protein TTG-2, LIM domain only protein 2, LMO-2, RBTN2, RBTNL1, ...
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Disease relevance of LMO2


High impact information on LMO2

  • The LIM domain protein rbtn2 is associated with T cell acute leukemias [5].
  • The homozygous rbtn2 null mutation leads to failure of yolk sac erythropoiesis and embryonic lethality around E10 [5].
  • Cooperation between the stem cell leukemia (SCL) transcription factor and its nuclear partners LMO1 or LMO2 induces aggressive T cell acute lymphoblastic leukemia when inappropriately expressed in T cells [6].
  • Most importantly, we show that the t(11;14)(p13;q32) translocation involving LMO2 is present at strikingly high frequency in normal human thymus, and that the recombinogenic potential conferred by the LMO2 cryptic site is directly predictive of the in vivo level of translocation at that locus [7].
  • LMO2 and LMO4 are members of a small family of nuclear transcriptional regulators that are important for both normal development and disease processes [8].

Chemical compound and disease context of LMO2


Biological context of LMO2


Anatomical context of LMO2


Associations of LMO2 with chemical compounds

  • The use of yeast assays with RBTN2 shows that RBTN2 forms homodimers and that the NH2-terminal 27 amino acids are sufficient to facilitate transcriptional transactivation [17].
  • Addition of LiCl to ATRA treatment restored the capacity of both Scl- and Rbtn2-expressing cells to respond to the retinoid in a synergistic manner [9].

Physical interactions of LMO2


Regulatory relationships of LMO2

  • We have also shown that hBex2 can enhance the transcriptional activity of LMO2 in vivo [21].
  • LMO2 has been shown to cause tumours when aberrantly expressed and to be able to heterodimerise with TAL1 to facilitate tumour development [22].

Other interactions of LMO2

  • RBTN1 and RBTN2 encode highly related proteins that possess cysteine-rich LIM motifs [23].
  • The oncogenic functions of LMO1 and LMO2 are thought to be mediated by interaction with LDB1 since they form a multimeric protein complex(es) [10].
  • The interleukin-2 receptor gamma chain (IL2Rgamma), which is mutated in SCID-X1, has been proposed as a cooperating oncogene to LMO2 [3].
  • Instead, restoration of normal IL7-receptor signaling may allow progression of T-cell development to stages where ectopic LMO2 expression causes aberrant thymocyte growth.Leukemia (2007) 21, 754-763. doi:10.1038/sj.leu.2404563; published online 1 February 2007 [3].
  • Using electrophoretic mobility shift assay, we have demonstrated the physical interaction of hBex2 and LMO2 as part of a DNA-binding protein complex [21].

Analytical, diagnostic and therapeutic context of LMO2


  1. Protein dimerization between Lmo2 (Rbtn2) and Tal1 alters thymocyte development and potentiates T cell tumorigenesis in transgenic mice. Larson, R.C., Lavenir, I., Larson, T.A., Baer, R., Warren, A.J., Wadman, I., Nottage, K., Rabbitts, T.H. EMBO J. (1996) [Pubmed]
  2. Identification of the Key LMO2-binding Determinants on Ldb1. Ryan, D.P., Sunde, M., Kwan, A.H., Marianayagam, N.J., Nancarrow, A.L., Vanden Hoven, R.N., Thompson, L.S., Baca, M., Mackay, J.P., Visvader, J.E., Matthews, J.M. J. Mol. Biol. (2006) [Pubmed]
  3. Ectopic retroviral expression of LMO2, but not IL2Rgamma, blocks human T-cell development from CD34+ cells: implications for leukemogenesis in gene therapy. Pike-Overzet, K., de Ridder, D., Weerkamp, F., Baert, M.R., Verstegen, M.M., Brugman, M.H., Howe, S.J., Reinders, M.J., Thrasher, A.J., Wagemaker, G., van Dongen, J.J., Staal, F.J. Leukemia (2007) [Pubmed]
  4. Different chromosomal breakpoints impact the level of LMO2 expression in T-ALL. Dik, W.A., Nadel, B., Przybylski, G.K., Asnafi, V., Grabarczyk, P., Navarro, J.M., Verhaaf, B., Schmidt, C.A., Macintyre, E.A., van Dongen, J.J., Langerak, A.W. Blood (2007) [Pubmed]
  5. The oncogenic cysteine-rich LIM domain protein rbtn2 is essential for erythroid development. Warren, A.J., Colledge, W.H., Carlton, M.B., Evans, M.J., Smith, A.J., Rabbitts, T.H. Cell (1994) [Pubmed]
  6. SCL and LMO1 alter thymocyte differentiation: inhibition of E2A-HEB function and pre-T alpha chain expression. Herblot, S., Steff, A.M., Hugo, P., Aplan, P.D., Hoang, T. Nat. Immunol. (2000) [Pubmed]
  7. V(D)J-mediated translocations in lymphoid neoplasms: a functional assessment of genomic instability by cryptic sites. Marculescu, R., Le, T., Simon, P., Jaeger, U., Nadel, B. J. Exp. Med. (2002) [Pubmed]
  8. Structural basis for the recognition of ldb1 by the N-terminal LIM domains of LMO2 and LMO4. Deane, J.E., Mackay, J.P., Kwan, A.H., Sum, E.Y., Visvader, J.E., Matthews, J.M. EMBO J. (2003) [Pubmed]
  9. Combination of all-trans retinoic acid and lithium chloride surmounts a retinoid differentiation block induced by expression of Scl and Rbtn2 transcription factors in myeloid leukemia cells. Rice, A.M., Li, J., Sartorelli, A.C. Leuk. Res. (2004) [Pubmed]
  10. Characterization of the Lmo4 gene encoding a LIM-only protein: genomic organization and comparative chromosomal mapping. Tse, E., Grutz, G., Garner, A.A., Ramsey, Y., Carter, N.P., Copeland, N., Gilbert, D.J., Jenkins, N.A., Agulnick, A., Forster, A., Rabbitts, T.H. Mamm. Genome (1999) [Pubmed]
  11. T-cell oncogene rhombotin-2 interacts with retinoblastoma-binding protein 2. Mao, S., Neale, G.A., Goorha, R.M. Oncogene (1997) [Pubmed]
  12. The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation. Visvader, J.E., Mao, X., Fujiwara, Y., Hahm, K., Orkin, S.H. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  13. Recurrent retroviral vector integration at the Mds1/Evi1 locus in nonhuman primate hematopoietic cells. Calmels, B., Ferguson, C., Laukkanen, M.O., Adler, R., Faulhaber, M., Kim, H.J., Sellers, S., Hematti, P., Schmidt, M., von Kalle, C., Akagi, K., Donahue, R.E., Dunbar, C.E. Blood (2005) [Pubmed]
  14. Mutational analysis of the LMO4 gene, encoding a BRCA1-interacting protein, in breast carcinomas. Sutherland, K.D., Visvader, J.E., Choong, D.Y., Sum, E.Y., Lindeman, G.J., Campbell, I.G. Int. J. Cancer (2003) [Pubmed]
  15. Identification and characterization of LMO4, an LMO gene with a novel pattern of expression during embryogenesis. Kenny, D.A., Jurata, L.W., Saga, Y., Gill, G.N. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  16. The LIM domain-only protein LMO4 is required for neural tube closure. Lee, S.K., Jurata, L.W., Nowak, R., Lettieri, K., Kenny, D.A., Pfaff, S.L., Gill, G.N. Mol. Cell. Neurosci. (2005) [Pubmed]
  17. Functional diversity of LIM proteins: amino-terminal activation domains in the oncogenic proteins RBTN1 and RBTN2. Sánchez-García, I., Axelson, H., Rabbitts, T.H. Oncogene (1995) [Pubmed]
  18. The LIM-only protein LMO4 modulates the transcriptional activity of HEN1. Manetopoulos, C., Hansson, A., Karlsson, J., Jönsson, J.I., Axelson, H. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  19. LIM-only protein Lmo2 forms a protein complex with erythroid transcription factor GATA-1. Osada, H., Grutz, G.G., Axelson, H., Forster, A., Rabbitts, T.H. Leukemia (1997) [Pubmed]
  20. The LIM domain protein Lmo2 binds to AF6, a translocation partner of the MLL oncogene. Bégay-Müller, V., Ansieau, S., Leutz, A. FEBS Lett. (2002) [Pubmed]
  21. Human Bex2 interacts with LMO2 and regulates the transcriptional activity of a novel DNA-binding complex. Han, C., Liu, H., Liu, J., Yin, K., Xie, Y., Shen, X., Wang, Y., Yuan, J., Qiang, B., Liu, Y.J., Peng, X. Nucleic Acids Res. (2005) [Pubmed]
  22. Chromosomal translocations and leukaemia: a role for LMO2 in T cell acute leukaemia, in transcription and in erythropoiesis. Rabbitts, T.H., Axelson, H., Forster, A., Grutz, G., Lavenir, I., Larson, R., Osada, H., Valge-Archer, V., Wadman, I., Warren, A. Leukemia (1997) [Pubmed]
  23. Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. Wadman, I., Li, J., Bash, R.O., Forster, A., Osada, H., Rabbitts, T.H., Baer, R. EMBO J. (1994) [Pubmed]
  24. The significance of LMO2 expression in the progression of prostate cancer. Ma, S., Guan, X., Beh, P., Wong, K., Chan, Y., Yuen, H., Vielkind, J., Chan, K. J. Pathol. (2007) [Pubmed]
  25. A single ancestral gene of the human LIM domain oncogene family LMO in Drosophila: characterization of the Drosophila Dlmo gene. Zhu, T.H., Bodem, J., Keppel, E., Paro, R., Royer-Pokora, B. Oncogene (1995) [Pubmed]
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