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Gene Review

CSRP3  -  cysteine and glycine-rich protein 3...

Homo sapiens

Synonyms: CLP, CMD1M, CMH12, CRP3, Cardiac LIM protein, ...
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Disease relevance of CSRP3


Psychiatry related information on CSRP3

  • Further, gray matter volume of the STP was inversely correlated with IQ and language test scores in CLP subjects [5].

High impact information on CSRP3

  • LMO2 and LMO4 are members of a small family of nuclear transcriptional regulators that are important for both normal development and disease processes [6].
  • LMO4 is developmentally regulated in the mammary gland and has been implicated in breast oncogenesis [6].
  • We have shown previously that the major late promoter of Ad12 DNA (Ad12 MLP; nucleotides -228 to +435 relative to nucleotide +1 as the site of transcriptional initiation) does not function in uninfected or in Ad12-infected hamster BHK21 cells [7].
  • The localization of this cap site in the nucleotide sequence of the Ad12 MLP indicates the similarity to the comparable start site in the MLP of Ad2 DNA.(ABSTRACT TRUNCATED AT 250 WORDS)[7]
  • It is also demonstrated that in the nucleotide -228 to +248 MLP construct, transcription is initiated at the authentic Ad12 MLP cap site after the transfection of both hamster and human cells [7].

Chemical compound and disease context of CSRP3

  • During MLP, uterine bleeding occurred in all subjects within 36-72 h of the first dose of RU 486, but no histological changes were discernible on endometrial biopsy taken 12-24 h before bleeding [8].
  • METHODS: Male NMRI-mice were subjected to sham operation or to sepsis (caecal ligation and puncture, CLP) following administration of either the non-selective beta-adrenergic antagonist propranolol (0.5mg/kg s.c. every 12h in 1ml vehicle) or saline 0.9% (1ml s.c. every 12h) [9].
  • Monoclonal antibody COC166-9 against ovarian carcinoma was conjugated with adriamycin or cisplatinum entraped in liposomes as immunochemical liposomes MLA and MLP respectively [10].

Biological context of CSRP3


Anatomical context of CSRP3

  • Confocal microscopy studies also reveal that MLP co-localizes with beta-spectrin at the sarcolemma overlying the Z- and M-lines of myofibrils in both cardiac and skeletal muscle tissue [11].
  • LMO4 can interact with Smad proteins and modulate transforming growth factor-beta signaling in epithelial cells [1].
  • Therefore, MLP dowregulation occurring during gene reprogramming may critically contribute to mechanical failure of the myocardium [2].
  • Activity measurements of these constructs in BHK21 and in HeLa cells have located the presumptive mitigator element to the Ad12 sequence between nucleotides +320 and +352 of the MLP [7].
  • We conclude that both UEFh and UEFy activate transcription from the Ad2 MLP upon binding to the upstream element, whatever is the in vitro cell-free system (yeast or HeLa) [14].

Associations of CSRP3 with chemical compounds

  • Two different in vitro qualitative assays-yeast two-hybrid and glutathion S-transferase pull-down competition-were performed in order to investigate functional changes in Tcap's interaction with MLP, titin, and calsarcin-1 caused by the identified mutations and a reported DCM-associated mutation, R87Q [15].
  • Short-term or long-term treatment with Ro-31-8220 in a mouse model of heart failure due to deletion of the muscle lim protein gene significantly augmented cardiac contractility and restored pump function [16].
  • Cn H99 and Cn MLP stimulated PMN to produce similar amounts of O2- and H2O2 [17].
  • We used a mannitol low-producing Cn mutant (Cn MLP) and its wild-type parent (Cn H99) to examine the role of ROIs distal to H2O2 in PMN killing and to determine whether mannitol produced by Cn protects the fungus against ROIs [17].
  • Finally, H2O2 alone killed similar numbers of Cn H99 and Cn MLP cells, but oxidants generated by FeSO4 (1 microM), H2O2 (10 microM), and iodide (1 to 3 microM) killed significantly more Cn MLP than Cn H99 cells in 1 h (p less than 0.05) [17].

Physical interactions of CSRP3

  • The Z-disc plays a role in establishing the mechanical coupling of sarcomeric contraction and stretching, with the titin/Tcap/MLP complex serving as a mechanical stretch sensor [15].
  • Our data also show that, in comparison to wild-type MLP, the capacity of the mutated MLP protein to bind both N-RAP and alpha-actinin is significantly decreased [3].

Regulatory relationships of CSRP3


Other interactions of CSRP3


Analytical, diagnostic and therapeutic context of CSRP3

  • We describe here the molecular cloning and characterization of a developmentally regulated smooth muscle LIM protein, SmLIM, that is expressed preferentially in the rat aorta [22].
  • The authors previously reported that early, moderate-dose IL-12 therapy in a mouse model of burn injury restored resistance to a later infectious challenge (cecal ligation and puncture, CLP) [23].
  • Perfusions with adenoviral vectors bearing a weaker promoter (MLP promoter) driving the rIL-3 beta gene did not result in antitumor responses, suggesting that the rIL-3 beta-mediated antitumor effect depends on the amount of rIL-3 beta protein expressed by the infected cells [24].
  • We analyzed the CRP 3' untranslated variant with a mutagenic separated PCR assay [25].
  • Using the techniques of biochemical subcellular fractionation and immunocytochemistry, we found MLP exhibits oligomerization in the membrane and cytoskeleton of cultured cardiac rat neonatal myocytes [26].


  1. LMO4 can interact with Smad proteins and modulate transforming growth factor-beta signaling in epithelial cells. Lu, Z., Lam, K.S., Wang, N., Xu, X., Cortes, M., Andersen, B. Oncogene (2006) [Pubmed]
  2. Downregulation and nuclear relocation of MLP during the progression of right ventricular hypertrophy induced by chronic pressure overload. Ecarnot-Laubriet, A., De Luca, K., Vandroux, D., Moisant, M., Bernard, C., Assem, M., Rochette, L., Teyssier, J.R. J. Mol. Cell. Cardiol. (2000) [Pubmed]
  3. Decreased interactions of mutant muscle LIM protein (MLP) with N-RAP and alpha-actinin and their implication for hypertrophic cardiomyopathy. Gehmlich, K., Geier, C., Osterziel, K.J., Van der Ven, P.F., Fürst, D.O. Cell Tissue Res. (2004) [Pubmed]
  4. A CCAAT box sequence in the adenovirus major late promoter functions as part of an RNA polymerase II termination signal. Connelly, S., Manley, J.L. Cell (1989) [Pubmed]
  5. Structure and function of the superior temporal plane in adult males with cleft lip and palate: pathologic enlargement with no relationship to childhood hearing deficits. Shriver, A.S., Canady, J., Richman, L., Andreasen, N.C., Nopoulos, P. Journal of child psychology and psychiatry, and allied disciplines. (2006) [Pubmed]
  6. 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]
  7. A mitigator sequence in the downstream region of the major late promoter of adenovirus type 12 DNA. Zock, C., Doerfler, W. EMBO J. (1990) [Pubmed]
  8. Luteal contraception. Yen, S., Garzo, G., Liu, J. Contraception. (1987) [Pubmed]
  9. beta-Adrenergic blockade during systemic inflammation: Impact on cellular immune functions and survival in a murine model of sepsis. Schmitz, D., Wilsenack, K., Lendemanns, S., Schedlowski, M., Oberbeck, R. Resuscitation (2007) [Pubmed]
  10. Target therapy of ovarian carcinoma by monoclonal antibodies bearing chemical drugs entrapped in liposomes. Qian, H.N., Li, W.J. Chin. Med. J. (1993) [Pubmed]
  11. The muscle regulatory and structural protein MLP is a cytoskeletal binding partner of betaI-spectrin. Flick, M.J., Konieczny, S.F. J. Cell. Sci. (2000) [Pubmed]
  12. Characterization of a human cardiac gene which encodes for a LIM domain protein and is developmentally expressed in myocardial development. Fung, Y.W., Wang, R., Liew, C.C. J. Mol. Cell. Cardiol. (1996) [Pubmed]
  13. Mapping of a human LIM protein (CLP) to human chromosome 11p15.1 by fluorescence in situ hybridization. Fung, Y.W., Wang, R.X., Heng, H.H., Liew, C.C. Genomics (1995) [Pubmed]
  14. A yeast homolog of the human UEF stimulates transcription from the adenovirus 2 major late promoter in yeast and in mammalian cell-free systems. Moncollin, V., Stalder, R., Verdier, J.M., Sentenac, A., Egly, J.M. Nucleic Acids Res. (1990) [Pubmed]
  15. Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy. Hayashi, T., Arimura, T., Itoh-Satoh, M., Ueda, K., Hohda, S., Inagaki, N., Takahashi, M., Hori, H., Yasunami, M., Nishi, H., Koga, Y., Nakamura, H., Matsuzaki, M., Choi, B.Y., Bae, S.W., You, C.W., Han, K.H., Park, J.E., Knöll, R., Hoshijima, M., Chien, K.R., Kimura, A. J. Am. Coll. Cardiol. (2004) [Pubmed]
  16. Pharmacological- and gene therapy-based inhibition of protein kinase Calpha/beta enhances cardiac contractility and attenuates heart failure. Hambleton, M., Hahn, H., Pleger, S.T., Kuhn, M.C., Klevitsky, R., Carr, A.N., Kimball, T.F., Hewett, T.E., Dorn, G.W., Koch, W.J., Molkentin, J.D. Circulation (2006) [Pubmed]
  17. Oxidative killing of Cryptococcus neoformans by human neutrophils. Evidence that fungal mannitol protects by scavenging reactive oxygen intermediates. Chaturvedi, V., Wong, B., Newman, S.L. J. Immunol. (1996) [Pubmed]
  18. Genotype-phenotype relationships involving hypertrophic cardiomyopathy-associated mutations in titin, muscle LIM protein, and telethonin. Bos, J.M., Poley, R.N., Ny, M., Tester, D.J., Xu, X., Vatta, M., Towbin, J.A., Gersh, B.J., Ommen, S.R., Ackerman, M.J. Mol. Genet. Metab. (2006) [Pubmed]
  19. W4R variant in CSRP3 encoding muscle LIM protein in a patient with hypertrophic cardiomyopathy. Newman, B., Cescon, D., Woo, A., Rakowski, H., Erikkson, M.J., Sole, M., Wigle, E.D., Siminovitch, K.A. Mol. Genet. Metab. (2005) [Pubmed]
  20. The role of the cytoskeleton in heart failure. Hein, S., Kostin, S., Heling, A., Maeno, Y., Schaper, J. Cardiovasc. Res. (2000) [Pubmed]
  21. Controlled intermittent shortening contractions of a muscle-tendon complex: muscle fibre damage and effects on force transmission from a single head of rat EDL. Maas, H., Lehti, T.M., Tiihonen, V., Komulainen, J., Huijing, P.A. J. Muscle Res. Cell. Motil. (2005) [Pubmed]
  22. Molecular cloning and characterization of SmLIM, a developmentally regulated LIM protein preferentially expressed in aortic smooth muscle cells. Jain, M.K., Fujita, K.P., Hsieh, C.M., Endege, W.O., Sibinga, N.E., Yet, S.F., Kashiki, S., Lee, W.S., Perrella, M.A., Haber, E., Lee, M.E. J. Biol. Chem. (1996) [Pubmed]
  23. Injury induces deficient interleukin-12 production, but interleukin-12 therapy after injury restores resistance to infection. Göebel, A., Kavanagh, E., Lyons, A., Saporoschetz, I.B., Soberg, C., Lederer, J.A., Mannick, J.A., Rodrick, M.L. Ann. Surg. (2000) [Pubmed]
  24. Adenovirus-mediated interleukin 3 beta gene transfer by isolated limb perfusion inhibits growth of limb sarcoma in rats. de Wilt, J.H., Bout, A., Eggermont, A.M., van Tiel, S.T., de Vries, M.W., ten Hagen, T.L., de Roos, W.K., Valerio, D., van der Kaaden, M.E. Hum. Gene Ther. (2001) [Pubmed]
  25. The C-Reactive Protein +1444C/T Alteration Modulates the Inflammation and Coagulation Response in Human Endotoxemia. Marsik, C., Sunder-Plassmann, R., Jilma, B., Kovar, F.M., Mannhalter, C., Wagner, O., Rumpold, H., Endler, G. Clin. Chem. (2006) [Pubmed]
  26. Cardiac dysfunction and heart failure are associated with abnormalities in the subcellular distribution and amounts of oligomeric muscle LIM protein. Boateng, S.Y., Belin, R.J., Geenen, D.L., Margulies, K.B., Martin, J.L., Hoshijima, M., de Tombe, P.P., Russell, B. Am. J. Physiol. Heart Circ. Physiol. (2007) [Pubmed]
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