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Gene Review

PDLIM5  -  PDZ and LIM domain 5

Homo sapiens

Synonyms: ENH, ENH1, Enh, Enigma homolog, Enigma-like PDZ and LIM domains protein, ...
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Disease relevance of PDLIM5

  • ENH is up-regulated during neural differentiation, and its ectopic expression in neuroblastoma cells leads to translocation of Id2 from the nucleus to the cytoplasm, with consequent inactivation of transcriptional and cell-cycle-promoting functions of Id2 [1].
  • Finally, the differentiated neural crest-derived tumor ganglioneuroblastoma coexpresses Id2 and ENH in the cytoplasm of ganglionic cells [1].
  • Nail patella syndrome (NPS) is caused by mutations in LMX1B, encoding a LIM homeodomain transcription factor [2].
  • Chimeric transcripts were isolated from two lipomas in which HMGI-C DNA-binding domains (AT hook motifs) are fused to either a LIM or an acidic transactivation domain [3].
  • The LIM domain protein rbtn2 is associated with T cell acute leukemias [4].

Psychiatry related information on PDLIM5

  • Gene expression and association analyses of LIM (PDLIM5) in bipolar disorder and schizophrenia [5].
  • They also suggest that ENH is a restraining factor of the oncogenic activity of Id proteins in neural tumors [1].
  • Recently, the LIM mRNA expression in postmortem brains and immortalized lymphoblastoid cells from mood disorder patients was reported to be changed and seems to be involved in its pathophysiology [6].

High impact information on PDLIM5


Chemical compound and disease context of PDLIM5

  • Conversely, silencing of ENH by RNA interference prevents cytoplasmic relocation of Id2 in neuroblastoma cells differentiated with retinoic acid [1].
  • Here we describe the use of commercially available precast 2-DE gels for performing nonreducing/non-urea 2-DE of proteins extracted from the human colon cancer cell line LIM 1215 with 0.3% Triton X-100 that permit the identification of antigens with conformational determinants by immunoblot analysis [12].
  • We report that, when 5-FU at 0.125 and 0.25 micrograms/ml was combined with SMS 201.995 at 10(-12) x 2 to 10(-8) x 2M, an enhanced inhibition of in-vitro growth of two human colorectal cancer cell lines (C170 and LIM 1215) was achieved [13].

Biological context of PDLIM5

  • A novel human gene cDNA was successfully cloned from the human fetal brain cDNA library constructed by our lab, and this gene was termed PDLIM5 after acquiring the agreement of HUGO [14].
  • CONCLUSIONS: These results suggest that PDLIM5 might play a role in genetic susceptibility to schizophrenia [15].
  • Due to very restricted knowledge on cytoskeletal changes in trophoblast, we analyzed the protein expression of an actin stress fiber-associated protein, the carboxy-terminal LIM domain protein (CLP36) [16].
  • LIM (PDLIM5) is a small protein that interacts with protein kinase C-epsilon and the N-type calcium channel alpha-1B subunit and modulates neuronal calcium signaling [6].
  • The LIM domain comprising two zinc-finger motifs is found in a variety of proteins and has been proposed to direct protein-protein interactions [17].

Anatomical context of PDLIM5


Associations of PDLIM5 with chemical compounds

  • Deletion analysis demonstrated that any single LIM domain of ENH associates with the NH2-terminal region of PKC [17].
  • Other regulatory mechanisms in animal cells include binding of phosphoinositides, phosphorylation by LIM kinases on a single serine, and changes in pH [20].
  • The protein encoded by lmx-1 also contains two amino-terminal cysteine/histidine-rich "LIM" domains [21].
  • PINCH, which contains an array of five LIM domains, has been implicated as a platform for multiple protein-protein interactions that mediate integrin signaling within focal adhesions [22].
  • Conserved cysteine and histidine residues in the LIM domains suggest a metal-binding role [23].

Other interactions of PDLIM5


Analytical, diagnostic and therapeutic context of PDLIM5

  • Western blot studies of muscle tissues using a non-isoform-specific anti-ENH antibody revealed that ENH4 is present only in skeletal muscle and that there is a specific distribution of ENH members between skeletal and cardiac muscles, which is different in human and mouse [26].
  • BACKGROUND: Results of recent DNA microarray analyses of postmortem brains of patients with schizophrenia revealed that expression of the PDZ and LIM domain 5 gene (PDLIM5) is increased [15].
  • Northern blot analysis revealed that 1.9 kb of the hENH messenger RNA was predominantly expressed in heart and skeletal muscle, while 5.6 kb of the hENH messenger RNA was ubiquitously expressed in various human tissues [27].
  • An emerging theme is that LIM proteins might function as biosensors that mediate communication between the cytosolic and the nuclear compartments [28].
  • Transfection analyses of sequential carboxyl-terminal truncations of the four individual LIM motifs and site-directed mutagenesis of LIM domains 1, 2, and 3, as well as deletion mutagenesis, revealed that the principal mechanism of targeting paxillin to focal adhesions is through LIM3 [29].


  1. The protein ENH is a cytoplasmic sequestration factor for Id2 in normal and tumor cells from the nervous system. Lasorella, A., Iavarone, A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  2. Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome. Morello, R., Zhou, G., Dreyer, S.D., Harvey, S.J., Ninomiya, Y., Thorner, P.S., Miner, J.H., Cole, W., Winterpacht, A., Zabel, B., Oberg, K.C., Lee, B. Nat. Genet. (2001) [Pubmed]
  3. Disruption of the architectural factor HMGI-C: DNA-binding AT hook motifs fused in lipomas to distinct transcriptional regulatory domains. Ashar, H.R., Fejzo, M.S., Tkachenko, A., Zhou, X., Fletcher, J.A., Weremowicz, S., Morton, C.C., Chada, K. Cell (1995) [Pubmed]
  4. 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]
  5. Gene expression and association analyses of LIM (PDLIM5) in bipolar disorder and schizophrenia. Kato, T., Iwayama, Y., Kakiuchi, C., Iwamoto, K., Yamada, K., Minabe, Y., Nakamura, K., Mori, N., Fujii, K., Nanko, S., Yoshikawa, T. Mol. Psychiatry (2005) [Pubmed]
  6. Gene expression and association analysis of LIM (PDLIM5) in major depression. Iga, J., Ueno, S., Yamauchi, K., Numata, S., Motoki, I., Tayoshi, S., Kinouchi, S., Ohta, K., Song, H., Morita, K., Rokutan, K., Tanabe, H., Sano, A., Ohmori, T. Neurosci. Lett. (2006) [Pubmed]
  7. Chromosomal translocations in lymphoid malignancies reveal novel proto-oncogenes. Korsmeyer, S.J. Annu. Rev. Immunol. (1992) [Pubmed]
  8. Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells. Hirota, T., Kunitoku, N., Sasayama, T., Marumoto, T., Zhang, D., Nitta, M., Hatakeyama, K., Saya, H. Cell (2003) [Pubmed]
  9. Migfilin and Mig-2 link focal adhesions to filamin and the actin cytoskeleton and function in cell shape modulation. Tu, Y., Wu, S., Shi, X., Chen, K., Wu, C. Cell (2003) [Pubmed]
  10. Crystal structure of a phosphatidylinositol 3-phosphate-specific membrane-targeting motif, the FYVE domain of Vps27p. Misra, S., Hurley, J.H. Cell (1999) [Pubmed]
  11. Induction of the LIM homeobox gene Lmx1 by WNT7a establishes dorsoventral pattern in the vertebrate limb. Riddle, R.D., Ensini, M., Nelson, C., Tsuchida, T., Jessell, T.M., Tabin, C. Cell (1995) [Pubmed]
  12. Nonreducing two-dimensional polyacrylamide gel electrophoretic analysis of human colonic proteins. Reid, G.E., Ji, H., Eddes, J.S., Moritz, R.L., Simpson, R.J. Electrophoresis (1995) [Pubmed]
  13. SMS 201.995 (Sandostatin) enhances in-vitro effects of 5-fluorouracil in colorectal cancer. Romani, R., Morris, D.L. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. (1995) [Pubmed]
  14. Cloning and identification of a novel human gene PDLIM5, a homolog of AD-associated neuronal thread protein (AD7c-NTP). Wu, M., Li, Y., Ji, C., Xu, J., Zheng, H., Zou, X., Gu, S., Lou, Y., Xie, Y., Mao, Y. DNA Seq. (2004) [Pubmed]
  15. A polymorphism in the PDLIM5 gene associated with gene expression and schizophrenia. Horiuchi, Y., Arai, M., Niizato, K., Iritani, S., Noguchi, E., Ohtsuki, T., Koga, M., Kato, T., Itokawa, M., Arinami, T. Biol. Psychiatry (2006) [Pubmed]
  16. Expression of the actin stress fiber-associated protein CLP36 in the human placenta. Miehe, U., Kadyrov, M., Neumaier-Wagner, P., Bartz, C., Rath, W., Huppertz, B. Histochem. Cell Biol. (2006) [Pubmed]
  17. Protein-protein interaction of zinc finger LIM domains with protein kinase C. Kuroda, S., Tokunaga, C., Kiyohara, Y., Higuchi, O., Konishi, H., Mizuno, K., Gill, G.N., Kikkawa, U. J. Biol. Chem. (1996) [Pubmed]
  18. Clik1: a novel kinase targeted to actin stress fibers by the CLP-36 PDZ-LIM protein. Vallenius, T., Mäkelä, T.P. J. Cell. Sci. (2002) [Pubmed]
  19. Expression of HSPF1 and LIM in the lymphoblastoid cells derived from patients with bipolar disorder and schizophrenia. Iwamoto, K., Bundo, M., Washizuka, S., Kakiuchi, C., Kato, T. J. Hum. Genet. (2004) [Pubmed]
  20. Proteins of the ADF/cofilin family: essential regulators of actin dynamics. Bamburg, J.R. Annu. Rev. Cell Dev. Biol. (1999) [Pubmed]
  21. Synergistic activation of the insulin gene by a LIM-homeo domain protein and a basic helix-loop-helix protein: building a functional insulin minienhancer complex. German, M.S., Wang, J., Chadwick, R.B., Rutter, W.J. Genes Dev. (1992) [Pubmed]
  22. Structural and functional insights into PINCH LIM4 domain-mediated integrin signaling. Velyvis, A., Vaynberg, J., Yang, Y., Vinogradova, O., Zhang, Y., Wu, C., Qin, J. Nat. Struct. Biol. (2003) [Pubmed]
  23. Cysteine-rich LIM domains of LIM-homeodomain and LIM-only proteins contain zinc but not iron. Archer, V.E., Breton, J., Sanchez-Garcia, I., Osada, H., Forster, A., Thomson, A.J., Rabbitts, T.H. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  24. Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders. Iwamoto, K., Kakiuchi, C., Bundo, M., Ikeda, K., Kato, T. Mol. Psychiatry (2004) [Pubmed]
  25. Molecular genetics of bipolar disorder and depression. Kato, T. Psychiatry Clin. Neurosci. (2007) [Pubmed]
  26. Characterization of a new human isoform of the enigma homolog family specifically expressed in skeletal muscle. Niederländer, N., Fayein, N.A., Auffray, C., Pomiès, P. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  27. Isolation, tissue expression, and chromosomal assignment of a human LIM protein gene, showing homology to rat enigma homologue (ENH). Ueki, N., Seki, N., Yano, K., Masuho, Y., Saito, T., Muramatsu, M. J. Hum. Genet. (1999) [Pubmed]
  28. The LIM domain: from the cytoskeleton to the nucleus. Kadrmas, J.L., Beckerle, M.C. Nat. Rev. Mol. Cell Biol. (2004) [Pubmed]
  29. Identification of LIM3 as the principal determinant of paxillin focal adhesion localization and characterization of a novel motif on paxillin directing vinculin and focal adhesion kinase binding. Brown, M.C., Perrotta, J.A., Turner, C.E. J. Cell Biol. (1996) [Pubmed]
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