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Gene Review

Fhl1  -  four and a half LIM domains 1

Mus musculus

Synonyms: FHL-1, Four and a half LIM domains protein 1, KyoT, KyoT1, KyoT2, ...
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Disease relevance of Fhl1

  • When expressed in F9 embryonal carcinoma cells, KyoT1 and KyoT2 were localized in the cytoplasm and the nucleus, respectively [1].
  • Taken together, these data indicate the potential importance of this FHL family in the development and maintenance of the cardiovascular system and striated muscle, and suggest that FHL1 may play a role in the development of heart disease [2].
  • It has been demonstrated that Borrelia hermsii, a causative agent of relapsing fever, produces a factor H (FH) and FH-like protein 1 (FHL-1) binding protein [3].
  • BetaAR blockade treatment reversed the cardiomyopathy and suppressed the increased expression of UCP2 and FHL1 in mice overexpressing Gsalpha [4].

High impact information on Fhl1

  • Thus, Rho signaling exerts an unexpectedly complex role in keratinocyte differentiation, which is coupled with induction of KyoT1/2, a LIM domain protein gene with a potentially important role in control of cell self renewal [5].
  • Strong expression of KyoT mRNAs was detected in skeletal muscle and lung, with a predominance of KyoT1 mRNA [1].
  • Collectively, these analyses indicate that FH/FHL-1 binding is a widespread virulence mechanism for B. hermsii and provide insight into the genetic and antigenic structure of FhbA [3].
  • Disruption of the actin cytoskeleton by cytochalasin D did not inhibit nuclear localization of SLIM1 in integrin-activated cells [6].
  • Overexpression of SLIM1 in Sol8 myoblasts inhibited cell adhesion and promoted cell spreading and migration [6].

Biological context of Fhl1


Anatomical context of Fhl1


Associations of Fhl1 with chemical compounds


Other interactions of Fhl1

  • Here, we describe the cloning and expression patterns of three members of the four and a half LIM domain-only protein family, FHL1, 2, and 3, from mouse [2].
  • Six genes were up-regulated in comparison to those in unfractured bones and these included three genes previously identified but never shown to be present in fractures, periostin, calumenin, and FHL-1 [12].

Analytical, diagnostic and therapeutic context of Fhl1

  • Sequence analysis indicated that FHL1C is the human homolog of murine KyoT2 [10].
  • The interaction between FHL1 and myosin-binding protein C was confirmed using co-immunoprecipitation of recombinant and endogenous proteins [13].
  • The Northern blot and RT-PCR results revealed that FHL1 is widely expressed in human tissues, including skeletal muscle and heart at a high level, albeit as a relatively low abundance transcript in brain, placenta, lung, liver, kidney, pancreas, and testis [10].
  • Western blot analysis using specific affinity-purified anti-SLIM1 antipeptide antibodies demonstrated a 32 kDa polypeptide in the aorta and atria of rabbit heart, but not in vena cava, interventricular septum or ventricular muscle [14].


  1. LIM protein KyoT2 negatively regulates transcription by association with the RBP-J DNA-binding protein. Taniguchi, Y., Furukawa, T., Tun, T., Han, H., Honjo, T. Mol. Cell. Biol. (1998) [Pubmed]
  2. Expression patterns of FHL/SLIM family members suggest important functional roles in skeletal muscle and cardiovascular system. Chu, P.H., Ruiz-Lozano, P., Zhou, Q., Cai, C., Chen, J. Mech. Dev. (2000) [Pubmed]
  3. Immunological and molecular analyses of the Borrelia hermsii factor H and factor H-like protein 1 binding protein, FhbA: demonstration of its utility as a diagnostic marker and epidemiological tool for tick-borne relapsing fever. Hovis, K.M., Schriefer, M.E., Bahlani, S., Marconi, R.T. Infect. Immun. (2006) [Pubmed]
  4. Common genomic response in different mouse models of beta-adrenergic-induced cardiomyopathy. Gaussin, V., Tomlinson, J.E., Depre, C., Engelhardt, S., Antos, C.L., Takagi, G., Hein, L., Topper, J.N., Liggett, S.B., Olson, E.N., Lohse, M.J., Vatner, S.F., Vatner, D.E. Circulation (2003) [Pubmed]
  5. Negative control of keratinocyte differentiation by Rho/CRIK signaling coupled with up-regulation of KyoT1/2 (FHL1) expression. Grossi, M., Hiou-Feige, A., Tommasi Di Vignano, A., Calautti, E., Ostano, P., Lee, S., Chiorino, G., Dotto, G.P. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  6. Skeletal muscle LIM protein 1 regulates integrin-mediated myoblast adhesion, spreading, and migration. Robinson, P.A., Brown, S., McGrath, M.J., Coghill, I.D., Gurung, R., Mitchell, C.A. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  7. Isolation and characterization of a new FHL1 variant (FHL1C) from porcine skeletal muscle. Krempler, A., Kollers, S., Fries, R., Brenig, B. Cytogenet. Cell Genet. (2000) [Pubmed]
  8. The LIM proteins FHL1 and FHL3 are expressed differently in skeletal muscle. Morgan, M.J., Madgwick, A.J. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  9. Transcriptional response to persistent beta2-adrenergic receptor signaling reveals regulation of phospholamban, which alters airway contractility. McGraw, D.W., Fogel, K.M., Kong, S., Litonjua, A.A., Kranias, E.G., Aronow, B.J., Liggett, S.B. Physiol. Genomics (2006) [Pubmed]
  10. Characterization of tissue-specific LIM domain protein (FHL1C) which is an alternatively spliced isoform of a human LIM-only protein (FHL1). Ng, E.K., Lee, S.M., Li, H.Y., Ngai, S.M., Tsui, S.K., Waye, M.M., Lee, C.Y., Fung, K.P. J. Cell. Biochem. (2001) [Pubmed]
  11. Influence of folic acid-fortified foods on folate status in a folate depletion-repletion rat model. O'Leary, K., Sheehy, P.J. Br. J. Nutr. (2001) [Pubmed]
  12. Gene expression of periostin in the early stage of fracture healing detected by cDNA microarray analysis. Nakazawa, T., Nakajima, A., Seki, N., Okawa, A., Kato, M., Moriya, H., Amizuka, N., Einhorn, T.A., Yamazaki, M. J. Orthop. Res. (2004) [Pubmed]
  13. Four and a half LIM protein 1 binds myosin-binding protein C and regulates myosin filament formation and sarcomere assembly. McGrath, M.J., Cottle, D.L., Nguyen, M.A., Dyson, J.M., Coghill, I.D., Robinson, P.A., Holdsworth, M., Cowling, B.S., Hardeman, E.C., Mitchell, C.A., Brown, S. J. Biol. Chem. (2006) [Pubmed]
  14. The cardiac expression of striated muscle LIM protein 1 (SLIM1) is restricted to the outflow tract of the developing heart. Brown, S., Biben, C., Ooms, L.M., Maimone, M., McGrath, M.J., Gurung, R., Harvey, R.P., Mitchell, C.A. J. Mol. Cell. Cardiol. (1999) [Pubmed]
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