Gene Symbol: Fhl1
Description: four and a half LIM domains 1
Alias: FHL-1, KyoT, RAM14-1, SLIM, SLIM-1, four and a half LIM domains protein 1, RBP-associated molecule 14-1, skeletal muscle LIM-protein 1
Species: mouse
Products:     Fhl1

Top Publications

  1. Sheikh F, Raskin A, Chu P, Lange S, Domenighetti A, Zheng M, et al. An FHL1-containing complex within the cardiomyocyte sarcomere mediates hypertrophic biomechanical stress responses in mice. J Clin Invest. 2008;118:3870-80 pubmed publisher
    ..Here, we found that four-and-a-half LIM domains 1 (FHL1) is part of a complex within the cardiomyocyte sarcomere that senses the biomechanical stress-induced responses ..
  2. Morgan M, Madgwick A. The LIM proteins FHL1 and FHL3 are expressed differently in skeletal muscle. Biochem Biophys Res Commun. 1999;255:245-50 pubmed
    ..The distribution of FHL mRNA expression within a variety of murine tissues is complex. Both FHL1 and FHL3 were expressed in a number of skeletal muscles while FHL2 was expressed at high levels in cardiac muscle...
  3. McGrath M, Cottle D, Nguyen M, Dyson J, Coghill I, Robinson P, et al. Four and a half LIM protein 1 binds myosin-binding protein C and regulates myosin filament formation and sarcomere assembly. J Biol Chem. 2006;281:7666-83 pubmed
    Four and a half LIM protein 1 (FHL1/SLIM1) is highly expressed in skeletal and cardiac muscle; however, the function of FHL1 remains unknown...
  4. Fimia G, De Cesare D, Sassone Corsi P. A family of LIM-only transcriptional coactivators: tissue-specific expression and selective activation of CREB and CREM. Mol Cell Biol. 2000;20:8613-22 pubmed
    ..The future identification of additional partners of FHL proteins is likely to reveal unappreciated aspects of tissue-specific transcriptional regulation. ..
  5. Wu S, Shih L, Lee J, Shen Y, Lee H. Estrogen enhances activity of Wnt signaling during osteogenesis by inducing Fhl1 expression. J Cell Biochem. 2015;116:1419-30 pubmed publisher
    ..In this study, we show that the Wnt agonist, LiCl, induced Fhl1 gene expression, which substantially enhanced osteoblast differentiation...
  6. Veith C, Marsh L, Wygrecka M, Rutschmann K, Seeger W, Weissmann N, et al. Paxillin regulates pulmonary arterial smooth muscle cell function in pulmonary hypertension. Am J Pathol. 2012;181:1621-33 pubmed publisher
    ..In addition, adhesion of PASMC to the extracellular matrix protein fibronectin was critically dependent on paxillin expression. To summarize, we identified paxillin as a new regulator protein of PASMC growth. ..
  7. Raskin A, Lange S, Banares K, Lyon R, Zieseniss A, Lee L, et al. A novel mechanism involving four-and-a-half LIM domain protein-1 and extracellular signal-regulated kinase-2 regulates titin phosphorylation and mechanics. J Biol Chem. 2012;287:29273-84 pubmed publisher
    ..complex at the cardiac-specific N2B region of titin that includes four-and-a-half LIM domain protein-1 (Fhl1) and components of the mitogen-activated protein signaling cascade, which impacted muscle compliance in Fhl1 knock-..
  8. Robinson P, Brown S, McGrath M, Coghill I, Gurung R, Mitchell C. Skeletal muscle LIM protein 1 regulates integrin-mediated myoblast adhesion, spreading, and migration. Am J Physiol Cell Physiol. 2003;284:C681-95 pubmed
    The skeletal muscle LIM protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. However, the function of SLIM1 is unknown...
  9. Greene W, Bahn S, Masson N, Rabbitts T. The T-cell oncogenic protein HOX11 activates Aldh1 expression in NIH 3T3 cells but represses its expression in mouse spleen development. Mol Cell Biol. 1998;18:7030-7 pubmed
    ..This result suggests that expression of Aldh1 protein is negatively regulated by Hox11 and that abnormal expression of Aldh1 in Hox11 null mice may cause loss of splenic precursor cells by aberrant retinoic acid metabolism. ..

Scientific Experts

More Information


  1. Friedrich F, Wilding B, Reischmann S, Crocini C, Lang P, Charron P, et al. Evidence for FHL1 as a novel disease gene for isolated hypertrophic cardiomyopathy. Hum Mol Genet. 2012;21:3237-54 pubmed publisher
    ..We hypothesized that FHL1, encoding four-and-a-half-LIM domains 1, could be another disease gene since it has been shown to cause distinct ..
  2. Cowling B, McGrath M, Nguyen M, Cottle D, Kee A, Brown S, et al. Identification of FHL1 as a regulator of skeletal muscle mass: implications for human myopathy. J Cell Biol. 2008;183:1033-48 pubmed publisher
    ..Four-and-a-half LIM protein 1 (FHL1) is mutated in several human myopathies, including reducing-body myopathy (RBM)...
  3. Stathopoulou K, Cuello F, Candasamy A, Kemp E, Ehler E, Haworth R, et al. Four-and-a-half LIM domains proteins are novel regulators of the protein kinase D pathway in cardiac myocytes. Biochem J. 2014;457:451-61 pubmed publisher
    ..In the present study we identify FHL1 (four-and-a-half LIM domains protein 1) and FHL2 as novel binding partners for PKD in cardiac myocytes...
  4. Williams T, Williams M, Kuick R, Misek D, McDonagh K, Hanash S, et al. Candidate downstream regulated genes of HOX group 13 transcription factors with and without monomeric DNA binding capability. Dev Biol. 2005;279:462-80 pubmed
    ..enzyme known to modulate tumor and normal cell motility and which is expressed in precartilaginous condensations; Fhl1, a transcription factor implicated in muscle cell differentiation and development; and M32486, a putative integral ..
  5. Ritie L, Spenlé C, Lacroute J, Bolcato Bellemin A, Lefebvre O, Bole Feysot C, et al. Abnormal Wnt and PI3Kinase signaling in the malformed intestine of lama5 deficient mice. PLoS ONE. 2012;7:e37710 pubmed publisher
    ..Thus deregulated adhesion to laminin-511 may be instrumental in diseases such as human pathologies of the gut where laminin-511 is abnormally expressed as it is shown here. ..
  6. Domenighetti A, Chu P, Wu T, Sheikh F, Gokhin D, Guo L, et al. Loss of FHL1 induces an age-dependent skeletal muscle myopathy associated with myofibrillar and intermyofibrillar disorganization in mice. Hum Mol Genet. 2014;23:209-25 pubmed publisher
    ..have provided evidences that sporadic or inherited missense mutations in four-and-a-half LIM domain protein 1 (FHL1), resulting in alterations in FHL1 protein expression, are associated with rare congenital myopathies, including ..
  7. Liang L, Zhang H, Liang J, Niu X, Zhang S, Feng L, et al. KyoT3, an isoform of murine FHL1, associates with the transcription factor RBP-J and represses the RBP-J-mediated transactivation. Biochim Biophys Acta. 2008;1779:805-10 pubmed publisher
    Previously, we have shown that KyoT2, an isoform of the four and a half LIM domain protein 1 (FHL1), modulates Notch signaling via repressing RBP-J-mediated transactivation...
  8. Christodoulou D, Wakimoto H, Onoue K, Eminaga S, Gorham J, DePalma S, et al. 5'RNA-Seq identifies Fhl1 as a genetic modifier in cardiomyopathy. J Clin Invest. 2014;124:1364-70 pubmed publisher
    ..92 genes had altered start-site usage in a mouse model of HCM, including four-and-a-half LIM domains protein 1 (Fhl1)...
  9. Bang M. Animal Models of Congenital Cardiomyopathies Associated With Mutations in Z-Line Proteins. J Cell Physiol. 2017;232:38-52 pubmed publisher
    ..Pros and cons of mouse models will be discussed and a future outlook will be given. J. Cell. Physiol. 232: 38-52, 2017. © 2016 Wiley Periodicals, Inc. ..
  10. Zhang S, Xu X, Liu M, Zhao H, Soares M, Barnstable C, et al. A biphasic pattern of gene expression during mouse retina development. BMC Dev Biol. 2006;6:48 pubmed
    ..We propose that large-scale changes in gene regulation during development are necessary for the final maturation and function of the retina. ..
  11. Chu P, Ruiz Lozano P, Zhou Q, Cai C, Chen J. Expression patterns of FHL/SLIM family members suggest important functional roles in skeletal muscle and cardiovascular system. Mech Dev. 2000;95:259-65 pubmed
    ..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...
  12. Collins K, Yuan Z, Kovall R. Structure and function of the CSL-KyoT2 corepressor complex: a negative regulator of Notch signaling. Structure. 2014;22:70-81 pubmed publisher
    ..These studies are important for understanding how CSL functions as both an activator and a repressor of transcription of Notch target genes. ..
  13. Kudo L, Karsten S, Chen J, Levitt P, Geschwind D. Genetic analysis of anterior posterior expression gradients in the developing mammalian forebrain. Cereb Cortex. 2007;17:2108-22 pubmed
    ..Two related transcription factors, previously not implicated in CNS development, Fhl1 and Fhl2, were observed to be enriched in posterior and anterior telencephalon, respectively...
  14. Isumi Y, Hirata T, Saitoh H, Miyakawa T, Murakami K, Kudoh G, et al. Transgenic overexpression of USP15 in the heart induces cardiac remodeling in mice. Biochem Biophys Res Commun. 2011;405:216-21 pubmed publisher
    We found a novel protein-protein interaction between ubiquitin-specific protease 15 (USP15) and skeletal muscle LIM protein 1 (SLIM1): USP15 and SLIM1 directly bound under cell-free conditions and co-immunoprecipitated from the lysates ..
  15. Lee J, Chien I, Lin W, Wu S, Wei B, Lee Y, et al. Fhl1 as a downstream target of Wnt signaling to promote myogenesis of C2C12 cells. Mol Cell Biochem. 2012;365:251-62 pubmed publisher
    ..This study reports that the murine four-and-a-half LIM domain 1 (Fhl1) could be stimulated by ?-catenin or LiCl treatment to induce myogenesis...
  16. Taniguchi Y, Furukawa T, Tun T, Han H, Honjo T. LIM protein KyoT2 negatively regulates transcription by association with the RBP-J DNA-binding protein. Mol Cell Biol. 1998;18:644-54 pubmed
    ..Using the yeast two-hybrid system, we isolated a LIM-only protein, KyoT, which physically interacts with RBP-J...
  17. Cottle D, McGrath M, Wilding B, Cowling B, Kane J, D Arcy C, et al. SLIMMER (FHL1B/KyoT3) interacts with the proapoptotic protein Siva-1 (CD27BP) and delays skeletal myoblast apoptosis. J Biol Chem. 2009;284:26964-77 pubmed publisher
    The fhl1 gene encoding four-and-a-half LIM protein-1 (FHL1) and its spliced isoform, SLIMMER, is mutated in reducing body myopathy, X-linked myopathy with postural muscle atrophy, scapuloperoneal myopathy, and rigid spine syndrome...
  18. Kwapiszewska G, Wygrecka M, Marsh L, Schmitt S, Trösser R, Wilhelm J, et al. Fhl-1, a new key protein in pulmonary hypertension. Circulation. 2008;118:1183-94 pubmed publisher
    ..Coimmunoprecipitation experiments identified Talin1 as a new interacting partner of Fhl-1. Protein screening identified Fhl-1 as a novel protein regulated in various forms of PH, including idiopathic pulmonary arterial hypertension. ..
  19. Wang J, Qin H, Liang J, Zhu Y, Liang L, Zheng M, et al. The transcriptional repression activity of KyoT2 on the Notch/RBP-J pathway is regulated by PIAS1-catalyzed SUMOylation. J Mol Biol. 2007;370:27-38 pubmed
    ..These results suggest that KyoT2 is a substrate of SUMO modification catalyzed by PIAS1, and that SUMOylation may modulate the transcriptional repression effect of KyoT2 on the Notch/RBP-J signaling pathway. ..
  20. Xu X, Fan Z, Liang C, Li L, Wang L, Liang Y, et al. A signature motif in LIM proteins mediates binding to checkpoint proteins and increases tumour radiosensitivity. Nat Commun. 2017;8:14059 pubmed publisher
    ..Here, we show that LIM domain-containing proteins, such as FHL1, increase inhibitory CDC25 phosphorylation by forming a complex with CHK2 and CDC25, and sequester CDC25 in the ..
  21. Emmanuele V, Kubota A, García Diaz B, Garone C, Akman H, Sánchez Gutiérrez D, et al. Fhl1 W122S causes loss of protein function and late-onset mild myopathy. Hum Mol Genet. 2015;24:714-26 pubmed publisher
    A member of the four-and-a-half-LIM (FHL) domain protein family, FHL1, is highly expressed in human adult skeletal and cardiac muscle...
  22. Ding L, Wang Z, Yan J, Yang X, Liu A, Qiu W, et al. Human four-and-a-half LIM family members suppress tumor cell growth through a TGF-beta-like signaling pathway. J Clin Invest. 2009;119:349-61 pubmed publisher
    ..The exact functions of each FHL protein in cancer development and progression remain unknown. Here we report that FHL1, FHL2, and FHL3 physically and functionally interact with Smad2, Smad3, and Smad4, important regulators of cancer ..
  23. Qin H, Du D, Zhu Y, Li J, Feng L, Liang Y, et al. The PcG protein HPC2 inhibits RBP-J-mediated transcription by interacting with LIM protein KyoT2. FEBS Lett. 2005;579:1220-6 pubmed
    ..Taken together, our results suggested that KyoT2 might inhibit the RBP-J-mediated transactivation through NIC by recruiting co-suppressors such as HPC2. ..
  24. Hu M, Ou Yang H, Han X, Ti X, Wu C. KyoT2 downregulates airway remodeling in asthma. Int J Clin Exp Pathol. 2015;8:14171-9 pubmed
    ..It is reasonable to assume that KyoT2 downregulates airway remodeling and resistance in asthmatic mice through a Hes1-dependent mechanism. Therefore, KyoT2 is a potential clinical treatment strategy for asthma. ..