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Gene Review

Pdlim5  -  PDZ and LIM domain 5

Mus musculus

Synonyms: 1110001A05Rik, AI987914, C87059, Enh, Enh1, ...
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Disease relevance of Pdlim5


High impact information on Pdlim5

  • LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein-protein interactions [5].
  • Using in vivo function and protein interaction assays, we found that Lhx3 binds directly to the LIM cofactor NLI to trigger V2 interneuron differentiation [5].
  • LIM homeodomain codes regulate the development of many cell types, though it is poorly understood how these factors control gene expression in a cell-specific manner [5].
  • LIM domains are required for both inhibitory effects on LIM homeodomain transcription factors and synergistic transcriptional activation events [6].
  • Neurons induced in explants derived from both diencephalic and telencephalic levels of the neural plate express the LIM homeodomain protein Isl-1, and these neurons possess distinct identities that match those of the ventral neurons generated in these two subdivisions of the forebrain in vivo [7].

Biological context of Pdlim5

  • Point mutation of either the PDZ or LIM domain was sufficient to reverse suppression of colony formation, but mutation of the PDZ domain alone was sufficient to abolish enhanced adhesion [8].
  • The phenotype could be rescued by a cypher form, which contains the PDZ domain and the ZM motif, but lacks all three LIM domains [9].
  • Motor neuron subtypes express unique combinations of LIM-type homeodomain factors that may act as intrinsic genetic regulators of the cytoskeletal events that mediate cell migration, axon navigation or both [10].
  • The LIM homeodomain (LIM-HD) proteins, which contain two tandem LIM domains followed by a homeodomain, are critical transcriptional regulators of embryonic development [11].
  • The LIM homeodomain protein ISL1 is expressed in all classes of islet cells in the adult and its expression in the embryo is initiated soon after the islet cells have left the cell cycle [12].

Anatomical context of Pdlim5

  • We identified Enigma, a PDZ and LIM domain-containing protein that was previously shown to be associated with the actin cytoskeleton [13].
  • Enigma localizes to actin filaments in fibroblasts via its PDZ domain, and actin-associated LIM protein binds to and colocalizes with the actin-binding protein alpha-actinin-2 at Z lines in skeletal muscle [14].
  • Thus, LIM homeodomain proteins act within motor neurons and cells that guide motor axons to establish the fidelity of a binary choice in axonal trajectory [15].
  • Towards cracking the code: LIM protein complexes in the spinal cord [16].
  • A major determinant in the cascades is an LIM homeodomain-containing gene, Lmx1b, which is required for the development of all 5-HT neurons in the central nervous system [17].

Associations of Pdlim5 with chemical compounds

  • Cypher is a member of a recently emerging family of proteins containing a PDZ domain at their NH(2) terminus and one or three LIM domains at their COOH terminus [18].
  • Specificity of LIM domain interactions with receptor tyrosine kinases [19].
  • LIM domains, Cys-rich motifs containing approximately 50 amino acids found in a variety of proteins, are proposed to direct protein*protein interactions [19].
  • To identify structural targets recognized by LIM domains, we have utilized random peptide library selection, the yeast two-hybrid system, and glutathione S-transferase fusions [19].
  • PINCH is a five LIM domain protein involved in the regulation of integrin-mediated cell adhesion [20].

Other interactions of Pdlim5

  • This interaction required the NPTY motif of APS and the LIM domains of Enigma [13].
  • Mitogenic signaling by Ret/ptc2 requires association with enigma via a LIM domain [21].
  • Together, our data suggest that Cypher1 may function as an adaptor in striated muscle to couple protein kinase C-mediated signaling, via its LIM domains, to the cytoskeleton (alpha-actinin-2) through its PDZ domain [22].

Analytical, diagnostic and therapeutic context of Pdlim5

  • Reciprocal substitution of the Enh2 domains in the two LTRs by site-directed mutagenesis shows that the rc-mos variant confers a 3-fold increment in in vivo promotor activity [23].
  • Molecular cloning, structure, and chromosomal localization of the mouse LIM/homeobox gene Lhx5 [24].
  • We report the cloning, sequence analysis, and developmental expression pattern of lim1, a member of the LIM class homeobox gene family in the mouse. lim1 cDNA encodes a predicted 406 amino acid protein that is 93% identical with the product of the Xenopus LIM class homeobox gene Xlim1 [25].
  • Reverse transcriptase-polymerase chain reactions (RT-PCR) performed on mouse pituitary mRNA using degenerate oligonucleotides based on the conserved LIM-domain sequences, allowed the extension of the 5' end of the sequence [26].
  • NMR titration experiments and site-directed mutagenesis indicate that this result is not dependent on specific interactions that require surface exposed residues on the RIL LIM domain, suggesting a stabilizing role in the association with PTP-BL [27].


  1. The LIM-only protein FHL2 interacts with beta-catenin and promotes differentiation of mouse myoblasts. Martin, B., Schneider, R., Janetzky, S., Waibler, Z., Pandur, P., Kühl, M., Behrens, J., von der Mark, K., Starzinski-Powitz, A., Wixler, V. J. Cell Biol. (2002) [Pubmed]
  2. The T cell leukemia LIM protein Lmo2 is necessary for adult mouse hematopoiesis. Yamada, Y., Warren, A.J., Dobson, C., Forster, A., Pannell, R., Rabbitts, T.H. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  3. Loss of the LIM domain protein Lmo4 in the mammary gland during pregnancy impedes lobuloalveolar development. Sum, E.Y., Shackleton, M., Hahm, K., Thomas, R.M., O'Reilly, L.A., Wagner, K.U., Lindeman, G.J., Visvader, J.E. Oncogene (2005) [Pubmed]
  4. Capture of a cellular transcriptional unit by a retrovirus: mode of provirus activation in embryonal carcinoma cells. Bonnerot, C., Legouy, E., Choulika, A., Nicolas, J.F. J. Virol. (1992) [Pubmed]
  5. LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein-protein interactions. Thaler, J.P., Lee, S.K., Jurata, L.W., Gill, G.N., Pfaff, S.L. Cell (2002) [Pubmed]
  6. RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex. Bach, I., Rodriguez-Esteban, C., Carrière, C., Bhushan, A., Krones, A., Rose, D.W., Glass, C.K., Andersen, B., Izpisúa Belmonte, J.C., Rosenfeld, M.G. Nat. Genet. (1999) [Pubmed]
  7. Sonic hedgehog induces the differentiation of ventral forebrain neurons: a common signal for ventral patterning within the neural tube. Ericson, J., Muhr, J., Placzek, M., Lints, T., Jessell, T.M., Edlund, T. Cell (1995) [Pubmed]
  8. Mystique is a new insulin-like growth factor-I-regulated PDZ-LIM domain protein that promotes cell attachment and migration and suppresses Anchorage-independent growth. Loughran, G., Healy, N.C., Kiely, P.A., Huigsloot, M., Kedersha, N.L., O'Connor, R. Mol. Biol. Cell (2005) [Pubmed]
  9. Zebrafish cypher is important for somite formation and heart development. van der Meer, D.L., Marques, I.J., Leito, J.T., Besser, J., Bakkers, J., Schoonheere, E., Bagowski, C.P. Dev. Biol. (2006) [Pubmed]
  10. Genetic and epigenetic mechanisms contribute to motor neuron pathfinding. Sharma, K., Leonard, A.E., Lettieri, K., Pfaff, S.L. Nature (2000) [Pubmed]
  11. Interactions of the LIM-domain-binding factor Ldb1 with LIM homeodomain proteins. Agulnick, A.D., Taira, M., Breen, J.J., Tanaka, T., Dawid, I.B., Westphal, H. Nature (1996) [Pubmed]
  12. Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. Ahlgren, U., Pfaff, S.L., Jessell, T.M., Edlund, T., Edlund, H. Nature (1997) [Pubmed]
  13. The interaction between the adaptor protein APS and Enigma is involved in actin organisation. Barrès, R., Gonzalez, T., Le Marchand-Brustel, Y., Tanti, J.F. Exp. Cell Res. (2005) [Pubmed]
  14. The PDZ domain of the LIM protein enigma binds to beta-tropomyosin. Guy, P.M., Kenny, D.A., Gill, G.N. Mol. Biol. Cell (1999) [Pubmed]
  15. Coordinate roles for LIM homeobox genes in directing the dorsoventral trajectory of motor axons in the vertebrate limb. Kania, A., Johnson, R.L., Jessell, T.M. Cell (2000) [Pubmed]
  16. Towards cracking the code: LIM protein complexes in the spinal cord. Sockanathan, S. Trends Neurosci. (2003) [Pubmed]
  17. Lmx1b is essential for the development of serotonergic neurons. Ding, Y.Q., Marklund, U., Yuan, W., Yin, J., Wegman, L., Ericson, J., Deneris, E., Johnson, R.L., Chen, Z.F. Nat. Neurosci. (2003) [Pubmed]
  18. Ablation of Cypher, a PDZ-LIM domain Z-line protein, causes a severe form of congenital myopathy. Zhou, Q., Chu, P.H., Huang, C., Cheng, C.F., Martone, M.E., Knoll, G., Shelton, G.D., Evans, S., Chen, J. J. Cell Biol. (2001) [Pubmed]
  19. Specificity of LIM domain interactions with receptor tyrosine kinases. Wu, R., Durick, K., Songyang, Z., Cantley, L.C., Taylor, S.S., Gill, G.N. J. Biol. Chem. (1996) [Pubmed]
  20. PINCH2 is a new five LIM domain protein, homologous to PINCHand localized to focal adhesions. Braun, A., Bordoy, R., Stanchi, F., Moser, M., Kostka G, G., Ehler, E., Brandau, O., Fässler, R. Exp. Cell Res. (2003) [Pubmed]
  21. Mitogenic signaling by Ret/ptc2 requires association with enigma via a LIM domain. Durick, K., Wu, R.Y., Gill, G.N., Taylor, S.S. J. Biol. Chem. (1996) [Pubmed]
  22. Cypher, a striated muscle-restricted PDZ and LIM domain-containing protein, binds to alpha-actinin-2 and protein kinase C. Zhou, Q., Ruiz-Lozano, P., Martone, M.E., Chen, J. J. Biol. Chem. (1999) [Pubmed]
  23. A variant binding sequence for transcription factor EBP-80 confers increased promoter activity on a retroviral long terminal repeat. Falzon, M., Kuff, E.L. J. Biol. Chem. (1990) [Pubmed]
  24. Molecular cloning, structure, and chromosomal localization of the mouse LIM/homeobox gene Lhx5. Bertuzzi, S., Sheng, H.Z., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Taira, M., Dawid, I.B., Westphal, H. Genomics (1996) [Pubmed]
  25. Expression patterns of the murine LIM class homeobox gene lim1 in the developing brain and excretory system. Fujii, T., Pichel, J.G., Taira, M., Toyama, R., Dawid, I.B., Westphal, H. Dev. Dyn. (1994) [Pubmed]
  26. The mouse homeoprotein mLIM-3 is expressed early in cells derived from the neuroepithelium and persists in adult pituitary. Seidah, N.G., Barale, J.C., Marcinkiewicz, M., Mattei, M.G., Day, R., Chrétien, M. DNA Cell Biol. (1994) [Pubmed]
  27. The interaction of PTP-BL PDZ domains with RIL: an enigmatic role for the RIL LIM domain. van den Berk, L.C., van Ham, M.A., te Lindert, M.M., Walma, T., Aelen, J., Vuister, G.W., Hendriks, W.J. Mol. Biol. Rep. (2004) [Pubmed]
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