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Gene Review

LMO3  -  LIM domain only 3 (rhombotin-like 2)

Homo sapiens

Synonyms: DAT1, LIM domain only protein 3, LMO-3, Neuronal-specific transcription factor DAT1, RBTN3, ...
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Disease relevance of LMO3

  • Human neuroblastoma SH-SY5Y cells stably overexpressing LMO3 showed a marked increase in cell growth, a promotion of colony formation in soft agar medium, and a rapid tumor growth in nude mice compared with the control transfectants [1].
  • In this context, collagens (COL7, 17) and cytokeratins (CK6, 15, 17) are preferentially induced in squamous cell carcinoma, whereas several transcription factors (TTF1, DAT1, TF-2) are exclusively elevated in adenocarcinomas [2].

Psychiatry related information on LMO3

  • BACKGROUND: The present study tests the hypothesis that the 9-repeat allele of the dopamine transporter gene (DAT1; SLC6A3) is more frequent in alcohol-dependent probands--and in particular those with severe withdrawal symptoms (seizures and/or delirium)--compared to nonalcoholics [3].
  • Objectives: To determine the degree of association of five single nucleotide polymorphisms at the 5'-untranslated region (5'-UTR) of the human dopamine transporter gene (hSLC6A3; hDAT1) in bipolar affective disorder [4].

High impact information on LMO3

  • Immunoprecipitation and immunostaining experiments showed that LMO3 was associated with HEN2 in mammalian cell nucleus [1].
  • In the present study, we have identified LMO3 and HEN2, which encodes a neuronal basic helix-loop-helix protein, as genes whose expression levels were higher in unfavorable neuroblastomas compared with those of favorable tumors [1].
  • The remarkable similarity between rbtn-1 and rbtn-3 proteins is parallelled in their expression patterns in mouse development, since both genes show high expression in restricted areas of the brain, but little lymphoid expression. rbtn-2 expression, however, is more ubiquitous [5].
  • Here we show that inhibition of phosphatidylinositol (PI) 3-kinase with LY294002 induces internalization of the human DAT (hDAT), thereby reducing transport capacity [6].
  • In addition, LY294002 caused a significant redistribution of the hDAT from the plasma membrane to the cytosol [6].

Biological context of LMO3

  • We have attempted to identify regions involved in the transcriptional regulation of the DAT1 (HUGO approved symbol SLC6A3) gene that may harbor functional variants predisposing to several neuropsychiatric disorders by examining haplotypes of various 5' and intronic regions for their effect on expression in a dopaminergic cell line [7].
  • Probes for the D13S25 marker on chromosome 13 band q14 and for the RBTN3 gene on chromosome 12 band p12-13, were used [8].

Anatomical context of LMO3

  • Acute treatment with LY294002 reduced the maximal rate of [(3) H]DA uptake in rat striatal synaptosomes and in human embryonic kidney (HEK) 293 cells stably expressing the hDAT (hDAT cells) [6].

Associations of LMO3 with chemical compounds

  • The dopamine transporter, the molecule responsible for presynaptic reuptake of dopamine and a major site of action of psychostimulant drugs, including cocaine, is encoded by locus SLC6A3 (alias DAT1) [9].

Analytical, diagnostic and therapeutic context of LMO3

  • The patch-clamp technique in the whole-cell configuration was used on Na(+) and DA-preloaded human embryonic kidney 293 cells stably transfected with the human DAT (hDAT cells) [10].


  1. LMO3 interacts with neuronal transcription factor, HEN2, and acts as an oncogene in neuroblastoma. Aoyama, M., Ozaki, T., Inuzuka, H., Tomotsune, D., Hirato, J., Okamoto, Y., Tokita, H., Ohira, M., Nakagawara, A. Cancer Res. (2005) [Pubmed]
  2. Identification and classification of differentially expressed genes in non-small cell lung cancer by expression profiling on a global human 59.620-element oligonucleotide array. Hofmann, H.S., Bartling, B., Simm, A., Murray, R., Aziz, N., Hansen, G., Silber, R.E., Burdach, S. Oncol. Rep. (2006) [Pubmed]
  3. DAT1 gene polymorphism in alcoholism: a family-based association study. Franke, P., Schwab, S.G., Knapp, M., Gänsicke, M., Delmo, C., Zill, P., Trixler, M., Lichtermann, D., Hallmayer, J., Wildenauer, D.B., Maier, W. Biol. Psychiatry (1999) [Pubmed]
  4. Association study of 5'-UTR polymorphisms of the human dopamine transporter gene with manic depression. St??ber, G., Sprandel, J., Schmidt, F., Faul, T., Jabs, B., Knapp, M. Bipolar disorders. (2006) [Pubmed]
  5. The rhombotin gene family encode related LIM-domain proteins whose differing expression suggests multiple roles in mouse development. Foroni, L., Boehm, T., White, L., Forster, A., Sherrington, P., Liao, X.B., Brannan, C.I., Jenkins, N.A., Copeland, N.G., Rabbitts, T.H. J. Mol. Biol. (1992) [Pubmed]
  6. PI 3-kinase regulation of dopamine uptake. Carvelli, L., Morón, J.A., Kahlig, K.M., Ferrer, J.V., Sen, N., Lechleiter, J.D., Leeb-Lundberg, L.M., Merrill, G., Lafer, E.M., Ballou, L.M., Shippenberg, T.S., Javitch, J.A., Lin, R.Z., Galli, A. J. Neurochem. (2002) [Pubmed]
  7. Promoter and intronic variants affect the transcriptional regulation of the human dopamine transporter gene. Greenwood, T.A., Kelsoe, J.R. Genomics (2003) [Pubmed]
  8. Deletion of chromosome 13 (band q14) but not trisomy 12 is a clonal event in B-chronic lymphocytic leukaemia (CLL). Jabbar, S.A., Ganeshaguru, K., Wickremasinghe, R.G., Hoffbrand, A.V., Foroni, L. Br. J. Haematol. (1995) [Pubmed]
  9. The dopamine transporter protein gene (SLC6A3): primary linkage mapping and linkage studies in Tourette syndrome. Gelernter, J., Vandenbergh, D., Kruger, S.D., Pauls, D.L., Kurlan, R., Pakstis, A.J., Kidd, K.K., Uhl, G. Genomics (1995) [Pubmed]
  10. Intracellular Ca2+ regulates amphetamine-induced dopamine efflux and currents mediated by the human dopamine transporter. Gnegy, M.E., Khoshbouei, H., Berg, K.A., Javitch, J.A., Clarke, W.P., Zhang, M., Galli, A. Mol. Pharmacol. (2004) [Pubmed]
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