Biology:FHL1

Short description: Mammalian protein found in humans

Generic protein structure example

Four and a half LIM domains protein 1 is a protein that in humans is encoded by the FHL1 gene.

Structure

LIM proteins, named for 'LIN11, ISL1, and MEC3,' are defined by the possession of a highly conserved double zinc finger motif called the LIM domain.

Role in muscle disorders

FHL1 has been shown to be heavily expressed in skeletal and cardiac muscles. In 2008 this was borne out by the discovery that defects in the FHL1 gene are responsible for a number of Muscular dystrophy-like muscle disorders, ranging from severe, childhood onset diseases through to adult-onset disorders similar to Limb girdle muscular dystrophy. At least 15 disease-causing mutations in this gene have been discovered. At present different research groups are using different terminology for these disorders, which include:

X-linked myopathy with postural muscle atrophy (XMPMA)

An adult-onset muscle disorder known to affect families in Austria and the UK.

Reducing body myopathy (RBM)

A rare disorder causing progressive muscular weakness characterized by aggresome-like inclusions in the myofibrils. The effects of the disorder can be either severe, with onset of weakness at approximately five years, or adult onset, with weakness occurring in the late 20s, early 30s.

Scapuloperoneal myopathy (SPM)

Another adult-onset muscle disorder, especially affecting the shoulder girdle and legs.

Further reading

• "The developmental regulation of a novel muscle LIM-protein". Biochemical and Biophysical Research Communications 212 (3): 840–6. Jul 1995. doi:10.1006/bbrc.1995.2045. PMID 7626119. 
• "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. Jan 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. Oct 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
• "Chromosomal mapping of two RBP-J-related genes: Kyo-T and RBP-L". Journal of Human Genetics 44 (1): 73–5. 1999. doi:10.1007/s100380050112. PMID 9929984. 
• "The LIM proteins FHL1 and FHL3 are expressed differently in skeletal muscle". Biochemical and Biophysical Research Communications 255 (2): 245–50. Feb 1999. doi:10.1006/bbrc.1999.0179. PMID 10049693. 
• "Genomic structure, tissue expression and chromosomal location of the LIM-only gene, SLIM1". Gene 232 (2): 203–7. May 1999. doi:10.1016/S0378-1119(99)00125-0. PMID 10352231. 
• "Characterization of two isoforms of the skeletal muscle LIM protein 1, SLIM1. Localization of SLIM1 at focal adhesions and the isoform slimmer in the nucleus of myoblasts and cytoplasm of myotubes suggests distinct roles in the cytoskeleton and in nuclear-cytoplasmic communication". The Journal of Biological Chemistry 274 (38): 27083–91. Sep 1999. doi:10.1074/jbc.274.38.27083. PMID 10480922. 
• "Characterization of a brain-specific nuclear LIM domain protein (FHL1B) which is an alternatively spliced variant of FHL1". Gene 237 (1): 253–63. Sep 1999. doi:10.1016/S0378-1119(99)00251-6. PMID 10524257. 
• "Characterization of tissue-specific LIM domain protein (FHL1C) which is an alternatively spliced isoform of a human LIM-only protein (FHL1)". Journal of Cellular Biochemistry 82 (1): 1–10. 2001. doi:10.1002/jcb.1110. PMID 11400158. 
• "Subcellular targeting of metabolic enzymes to titin in heart muscle may be mediated by DRAL/FHL-2". Journal of Cell Science 115 (Pt 24): 4925–36. Dec 2002. doi:10.1242/jcs.00181. PMID 12432079. 
• "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nature Biotechnology 21 (5): 566–9. May 2003. doi:10.1038/nbt810. PMID 12665801. 
• "Skeletal muscle LIM protein 1 (SLIM1/FHL1) induces alpha 5 beta 1-integrin-dependent myocyte elongation". American Journal of Physiology. Cell Physiology 285 (6): C1513–26. Dec 2003. doi:10.1152/ajpcell.00207.2003. PMID 12917103. 
• "RING1 inhibits transactivation of RBP-J by Notch through interaction with LIM protein KyoT2". Nucleic Acids Research 32 (4): 1492–501. 2004. doi:10.1093/nar/gkh295. PMID 14999091. 
• "The SRF target gene Fhl2 antagonizes RhoA/MAL-dependent activation of SRF". Molecular Cell 16 (6): 867–80. Dec 2004. doi:10.1016/j.molcel.2004.11.039. PMID 15610731. 
• "The PcG protein HPC2 inhibits RBP-J-mediated transcription by interacting with LIM protein KyoT2". FEBS Letters 579 (5): 1220–6. Feb 2005. doi:10.1016/j.febslet.2005.01.022. PMID 15710417. 

External links

• GeneReviews/NCBI/NIH/UW entry on Emery–Dreifuss muscular dystrophy
• FHL1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.