FHL1 explained

Four and a half LIM domains protein 1 is a protein that in humans is encoded by the FHL1 gene.^{[1] [2] [3]}

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.^[3]

Role in muscle disorders

FHL1 has been shown to be heavily expressed in skeletal and cardiac muscles.^[4] 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.^[5] 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.^[6]

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.^[7]

Scapuloperoneal myopathy (SPM): Another adult-onset muscle disorder, especially affecting the shoulder girdle and legs.^[8]

References

Further reading

• Morgan MJ, Madgwick AJ, Charleston B, Pell JM, Loughna PT . The developmental regulation of a novel muscle LIM-protein . Biochemical and Biophysical Research Communications . 212 . 3 . 840–6 . Jul 1995 . 7626119 . 10.1006/bbrc.1995.2045 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Tani S, Taniwaki M, Taniguchi Y, Minoguchi S, Kuroda K, Han H, Aoki T, Miyatake S, Hashimoto N, Honjo T . Chromosomal mapping of two RBP-J-related genes: Kyo-T and RBP-L . Journal of Human Genetics . 44 . 1 . 73–5 . 1999 . 9929984 . 10.1007/s100380050112 . free .
• Morgan MJ, Madgwick AJ . The LIM proteins FHL1 and FHL3 are expressed differently in skeletal muscle . Biochemical and Biophysical Research Communications . 255 . 2 . 245–50 . Feb 1999 . 10049693 . 10.1006/bbrc.1999.0179 .
• Greene WK, Baker E, Rabbitts TH, Kees UR . Genomic structure, tissue expression and chromosomal location of the LIM-only gene, SLIM1 . Gene . 232 . 2 . 203–7 . May 1999 . 10352231 . 10.1016/S0378-1119(99)00125-0 .
• Brown S, McGrath MJ, Ooms LM, Gurung R, Maimone MM, Mitchell CA . 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 . 10480922 . 10.1074/jbc.274.38.27083 . free .
• Lee SM, Li HY, Ng EK, Or SM, Chan KK, Kotaka M, Chim SS, Tsui SK, Waye MM, Fung KP, Lee CY . 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 . 10524257 . 10.1016/S0378-1119(99)00251-6 .
• Ng EK, Lee SM, Li HY, Ngai SM, Tsui SK, Waye MM, Lee CY, Fung KP . 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 . 11400158 . 10.1002/jcb.1110 . 25900444 .
• Lange S, Auerbach D, McLoughlin P, Perriard E, Schäfer BW, Perriard JC, Ehler E . 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 . 12432079 . 10.1242/jcs.00181 . free .
• Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J . Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides . Nature Biotechnology . 21 . 5 . 566–9 . May 2003 . 12665801 . 10.1038/nbt810 . 23783563 .
• McGrath MJ, Mitchell CA, Coghill ID, Robinson PA, Brown S . 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 . 12917103 . 10.1152/ajpcell.00207.2003 .
• Qin H, Wang J, Liang Y, Taniguchi Y, Tanigaki K, Han H . RING1 inhibits transactivation of RBP-J by Notch through interaction with LIM protein KyoT2 . Nucleic Acids Research . 32 . 4 . 1492–501 . 2004 . 14999091 . 390284 . 10.1093/nar/gkh295 .
• Philippar U, Schratt G, Dieterich C, Müller JM, Galgóczy P, Engel FB, Keating MT, Gertler F, Schüle R, Vingron M, Nordheim A . The SRF target gene Fhl2 antagonizes RhoA/MAL-dependent activation of SRF . Molecular Cell . 16 . 6 . 867–80 . Dec 2004 . 15610731 . 10.1016/j.molcel.2004.11.039 . 1721.1/83480 . free .
• Qin H, Du D, Zhu Y, Li J, Feng L, Liang Y, Han H . The PcG protein HPC2 inhibits RBP-J-mediated transcription by interacting with LIM protein KyoT2 . FEBS Letters . 579 . 5 . 1220–6 . Feb 2005 . 15710417 . 10.1016/j.febslet.2005.01.022 . 8214807 . free . 2005FEBSL.579.1220Q .

External links

• GeneReviews/NCBI/NIH/UW entry on Emery–Dreifuss muscular dystrophy

Notes and References

1. Morgan MJ, Madgwick AJ . Slim defines a novel family of LIM-proteins expressed in skeletal muscle . Biochemical and Biophysical Research Communications . 225 . 2 . 632–8 . Aug 1996 . 8753811 . 10.1006/bbrc.1996.1222 .
2. Lee SM, Tsui SK, Chan KK, Garcia-Barcelo M, Waye MM, Fung KP, Liew CC, Lee CY . Chromosomal mapping, tissue distribution and cDNA sequence of four-and-a-half LIM domain protein 1 (FHL1) . Gene . 216 . 1 . 163–70 . Aug 1998 . 9714789 . 10.1016/S0378-1119(98)00302-3 .
3. Web site: Entrez Gene: FHL1 four and a half LIM domains 1.
4. Lee SM, Tsui SK, Chan KK, Garcia-Barcelo M, Waye MM, Fung KP, Liew CC, Lee CY . Chromosomal mapping, tissue distribution and cDNA sequence of four-and-a-half LIM domain protein 1 (FHL1) . Gene . 216 . 1 . 163–70 . Aug 1998 . 9714789 . 10.1016/S0378-1119(98)00302-3 .
5. Šimčíková D, Heneberg P . Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases . Scientific Reports . 9 . 1 . 18577 . December 2019 . 31819097 . 6901466 . 10.1038/s41598-019-54976-4. 2019NatSR...918577S .
6. Windpassinger C, Schoser B, Straub V, Hochmeister S, Noor A, Lohberger B, Farra N, Petek E, Schwarzbraun T, Ofner L, Löscher WN, Wagner K, Lochmüller H, Vincent JB, Quasthoff S . An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1 . American Journal of Human Genetics . 82 . 1 . 88–99 . Jan 2008 . 18179888 . 2253986 . 10.1016/j.ajhg.2007.09.004 .
7. Schessl J, Zou Y, McGrath MJ, Cowling BS, Maiti B, Chin SS, Sewry C, Battini R, Hu Y, Cottle DL, Rosenblatt M, Spruce L, Ganguly A, Kirschner J, Judkins AR, Golden JA, Goebel HH, Muntoni F, Flanigan KM, Mitchell CA, Bönnemann CG . Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy . The Journal of Clinical Investigation . 118 . 3 . 904–12 . Mar 2008 . 18274675 . 2242623 . 10.1172/JCI34450 .
8. Quinzii CM, Vu TH, Min KC, Tanji K, Barral S, Grewal RP, Kattah A, Camaño P, Otaegui D, Kunimatsu T, Blake DM, Wilhelmsen KC, Rowland LP, Hays AP, Bonilla E, Hirano M . X-linked dominant scapuloperoneal myopathy is due to a mutation in the gene encoding four-and-a-half-LIM protein 1 . American Journal of Human Genetics . 82 . 1 . 208–13 . Jan 2008 . 18179901 . 2253963 . 10.1016/j.ajhg.2007.09.013 .