FHL1
FHL1（four and a half LIM domains 1）は、ヒトではFHL1遺伝子にコードされるタンパク質である[5][6][7]。
構造
[編集]FHL1はfour-and-a-half-LIM-onlyファミリーに属する。LIMドメインは、タンデムに並んだ、2つの高度に保存されたジンクフィンガーから構成され、各フィンガーは高度に保存された4つのシステイン残基によって1つの亜鉛原子を結合している。FHL1はこのLIMドメイン4個半から構成されている[7][8]。
筋疾患における役割
[編集]FHL1は骨格筋や心筋において高度に発現している[9]。2008年には、後述するいくつかの筋ジストロフィー様疾患において、FHL1遺伝子の欠陥が原因となっていることが発見された。少なくとも25種類の疾患原因変異がこの遺伝子に発見されている[10]。現時点では、FHL1遺伝子変異が原因となる筋疾患の臨床病型は次のように分類されているが、十分な検討がなされているわけではない[10][11]。
- X連鎖性姿勢筋萎縮症（X-linked myopathy with postural muscle atrophy、XMPMA） - オーストリアとイギリスの家系で報告されている成人発症型筋疾患[12]
- 還元小体ミオパチー（reducing body myopathy、RBM） - 筋線維中のアグリソーム様封入体によって特徴づけられる、進行性の筋低下が引き起こされる希少疾患。この疾患は、5歳ごろに筋力低下が始まる重篤なものである場合や、もしくは20代後半から30代前半にかけて筋力低下が始める成人発症型である場合もある[13]。
- 肩甲腓骨ミオパチー（scapuloperoneal myopathy、SPM） - 特に肩甲帯と脚に影響が生じる成人発症型筋疾患[14]
- エメリー・ドレイフス型筋ジストロフィー（EDMD）[15]
- 強直性脊椎症候群（RSS）[16]
出典
[編集]- ^ a b c GRCh38: Ensembl release 89: ENSG00000022267 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000023092 - Ensembl, May 2017
- ^ Human PubMed Reference:
- ^ Mouse PubMed Reference:
- ^ “Slim defines a novel family of LIM-proteins expressed in skeletal muscle”. Biochemical and Biophysical Research Communications 225 (2): 632–8. (Aug 1996). doi:10.1006/bbrc.1996.1222. PMID 8753811.
- ^ “Chromosomal mapping, tissue distribution and cDNA sequence of four-and-a-half LIM domain protein 1 (FHL1)”. Gene 216 (1): 163–70. (Aug 1998). doi:10.1016/S0378-1119(98)00302-3. PMID 9714789.
- ^ a b “Entrez Gene: FHL1 four and a half LIM domains 1”. 2024年8月17日閲覧。
- ^ Wei, Xiaofan; Zhang, Hongquan (2020-05-15). “Four and a half LIM domains protein 1 can be as a double-edged sword in cancer progression”. Cancer Biology & Medicine 17 (2): 270–281. doi:10.20892/j.issn.2095-3941.2019.0420. ISSN 2095-3941. PMC 7309467. PMID 32587768.
- ^ “Chromosomal mapping, tissue distribution and cDNA sequence of four-and-a-half LIM domain protein 1 (FHL1)”. Gene 216 (1): 163–70. (Aug 1998). doi:10.1016/S0378-1119(98)00302-3. PMID 9714789.
- ^ a b Cowling, Belinda S.; Cottle, Denny L.; Wilding, Brendan R.; D'Arcy, Colleen E.; Mitchell, Christina A.; McGrath, Meagan J. (2011-04). “Four and a half LIM protein 1 gene mutations cause four distinct human myopathies: a comprehensive review of the clinical, histological and pathological features”. Neuromuscular disorders: NMD 21 (4): 237–251. doi:10.1016/j.nmd.2011.01.001. ISSN 1873-2364. PMID 21310615.
- ^ Aohara, Kenta; Kimura, Hiroko; Takeda, Akitoshi; Izumiya, Yasuhiro; Nishino, Ichizo; Itoh, Yoshiaki (2022-09-28). “[Sibling cases of four and a half LIM domains 1 (FHL1) myopathy who developed respiratory failure without apparent limb weakness”]. Rinsho Shinkeigaku = Clinical Neurology 62 (9): 726–731. doi:10.5692/clinicalneurol.cn-001761. ISSN 1882-0654. PMID 36031379.
- ^ “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). doi:10.1016/j.ajhg.2007.09.004. PMC 2253986. PMID 18179888.
- ^ “Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy”. The Journal of Clinical Investigation 118 (3): 904–12. (Mar 2008). doi:10.1172/JCI34450. PMC 2242623. PMID 18274675.
- ^ “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). doi:10.1016/j.ajhg.2007.09.013. PMC 2253963. PMID 18179901.
- ^ Gueneau, Lucie; Bertrand, Anne T.; Jais, Jean-Philippe; Salih, Mustafa A.; Stojkovic, Tanya; Wehnert, Manfred; Hoeltzenbein, Maria; Spuler, Simone et al. (2009-09). “Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy”. American Journal of Human Genetics 85 (3): 338–353. doi:10.1016/j.ajhg.2009.07.015. ISSN 1537-6605. PMC 2771595. PMID 19716112.
- ^ Shalaby, Sherine; Hayashi, Yukiko K.; Goto, Kanako; Ogawa, Megumu; Nonaka, Ikuya; Noguchi, Satoru; Nishino, Ichizo (2008-12). “Rigid spine syndrome caused by a novel mutation in four-and-a-half LIM domain 1 gene (FHL1)”. Neuromuscular disorders: NMD 18 (12): 959–961. doi:10.1016/j.nmd.2008.09.012. ISSN 0960-8966. PMID 18952429.
関連文献
[編集]- “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. PMC 390284. 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. hdl:1721.1/83480. 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). Bibcode: 2005FEBSL.579.1220Q. doi:10.1016/j.febslet.2005.01.022. PMID 15710417.