LMNA：修订间差异

核纤层蛋白 A/C; Lamin A/C
	PDB rendering based on 1ifr.
有效结构
PDB	直系同源检索：PDBe, RCSB
PDB查询代码列表
	1IFR, 1IVT, 1X8Y, 2XV5, 2YPT, 3GEF, 3V4Q, 3V4W, 3V5B
标识
代号	LMNA; CDCD1; CDDC; CMD1A; CMT2B1; EMD2; FPL; FPLD; FPLD2; HGPS; IDC; LDP1; LFP; LGMD1B; LMN1; LMNC; LMNL1; PRO1
扩展标识	遗传学：150330 鼠基因：96794 同源基因：41321 ChEMBL: 1293235 GeneCards: LMNA Gene
基因本体论描述
分子功能	· structural molecule activity; · protein binding;
细胞成分	· nucleus; · nuclear envelope; · lamin filament; · nuclear lamina; · nucleoplasm; · cytoplasm; · cytosol; · intermediate filament; · perinuclear region of cytoplasm;
生物过程	· M phase of mitotic cell cycle; · mitotic prophase; · mitotic anaphase; · mitotic cell cycle; · apoptotic process; · cellular component disassembly involved in execution phase of apoptosis; · activation of signaling protein activity involved in unfolded protein response; · mitotic nuclear envelope disassembly; · mitotic nuclear envelope reassembly; · muscle organ development; · regulation of cell migration; · establishment or maintenance of microtubule cytoskeleton polarity; · endoplasmic reticulum unfolded protein response; · protein localization to nucleus; · sterol regulatory element binding protein import into nucleus; · regulation of apoptotic process; · cellular protein metabolic process; · ventricular cardiac muscle cell development; · cellular response to hypoxia; · positive regulation of cell aging;
	Sources: Amigo / QuickGO
RNA表达模式
	更多表达数据
直系同源体
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2014年6月20日 (五) 12:16的版本

核纤层蛋白 A/C（英語：Lamin A/C）是由人类基因LMNA 编码的蛋白质^[1]^[2]，属于核纤层蛋白家族。

功能

核纖層 consist of a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Through alternate splicing, this gene encodes three type A lamin isoforms.^[4]

Early in mitosis, MPF phosphorylates specific serine residues in all three nuclear lamins, causing depolymerization of the lamin intermediate filaments. The phosphorylated lamin B dimers remain associated with the nuclear membrane via their isoprenyl anchor. Lamin A is targeted to the nuclear membrane by an isoprenyl group but it is cleaved shortly after arriving at the membrane. It stays associated with the membrane through protein-protein interactions of itself and other membrane associated proteins, such as LAP1. Depolymerization of the nuclear lamins leads to disintegration of the nuclear envelope. Transfection experiments demonstrate that phosphorylation of human lamin A is required for lamin depolymerization, and thus for disassembly of the nuclear envelope, which normally occurs early in mitosis.

临床意义

Mutations in the LMNA gene are associated with several diseases, including Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, Restrictive dermopathy and Hutchinson-Gilford progeria syndrome. A truncated version of lamin A, commonly known as progerin, causes Hutchinson-Gilford progeria syndrome.^[5]^[6]

相互作用

LMNA has been shown to interact with:

参考文献

^ Kamat AK, Rocchi M, Smith DI, Miller OJ. Lamin A/C gene and a related sequence map to human chromosomes 1q12.1-q23 and 10. Somat. Cell Mol. Genet. March 1993, 19 (2): 203–8. PMID 8511676. doi:10.1007/BF01233534.
^ Wydner KL, McNeil JA, Lin F, Worman HJ, Lawrence JB. Chromosomal assignment of human nuclear envelope protein genes LMNA, LMNB1, and LBR by fluorescence in situ hybridization. Genomics. March 1996, 32 (3): 474–8. PMID 8838815. doi:10.1006/geno.1996.0146.
^ Coutinho HD, Falcão-Silva VS, Gonçalves GF, da Nóbrega RB. Molecular ageing in progeroid syndromes: Hutchinson-Gilford progeria syndrome as a model. Immun Ageing. 2009, 6: 4. PMC 2674425 . PMID 19379495. doi:10.1186/1742-4933-6-4.
^ Entrez Gene: LMNA lamin A/C.
^ Capell BC, Collins FS. Human laminopathies: nuclei gone genetically awry. Nat. Rev. Genet. December 2006, 7 (12): 940–52. PMID 17139325. doi:10.1038/nrg1906.
^ Rankin J, Ellard S. The laminopathies: a clinical review. Clin. Genet. October 2006, 70 (4): 261–74. PMID 16965317. doi:10.1111/j.1399-0004.2006.00677.x.
^ Tang K, Finley RL, Nie D, Honn KV. Identification of 12-lipoxygenase interaction with cellular proteins by yeast two-hybrid screening. Biochemistry. March 2000, 39 (12): 3185–91. PMID 10727209. doi:10.1021/bi992664v.
^ Wilkinson FL, Holaska JM, Zhang Z, Sharma A, Manilal S, Holt I, Stamm S, Wilson KL, Morris GE. Emerin interacts in vitro with the splicing-associated factor, YT521-B. Eur. J. Biochem. June 2003, 270 (11): 2459–66. PMID 12755701. doi:10.1046/j.1432-1033.2003.03617.x.
^ Lattanzi G, Cenni V, Marmiroli S, Capanni C, Mattioli E, Merlini L, Squarzoni S, Maraldi NM. Association of emerin with nuclear and cytoplasmic actin is regulated in differentiating myoblasts. Biochem. Biophys. Res. Commun. April 2003, 303 (3): 764–70. PMID 12670476. doi:10.1016/S0006-291X(03)00415-7.
^ Sakaki M, Koike H, Takahashi N, Sasagawa N, Tomioka S, Arahata K, Ishiura S. Interaction between emerin and nuclear lamins. J. Biochem. February 2001, 129 (2): 321–7. PMID 11173535. doi:10.1093/oxfordjournals.jbchem.a002860.
^ Clements L, Manilal S, Love DR, Morris GE. Direct interaction between emerin and lamin A. Biochem. Biophys. Res. Commun. January 2000, 267 (3): 709–14. PMID 10673356. doi:10.1006/bbrc.1999.2023.
^ Barton RM, Worman HJ. Prenylated prelamin A interacts with Narf, a novel nuclear protein. J. Biol. Chem. October 1999, 274 (42): 30008–18. PMID 10514485. doi:10.1074/jbc.274.42.30008.
^ Lloyd DJ, Trembath RC, Shackleton S. A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies. Hum. Mol. Genet. April 2002, 11 (7): 769–77. PMID 11929849. doi:10.1093/hmg/11.7.769.
^ Markiewicz E, Dechat T, Foisner R, Quinlan RA, Hutchison CJ. Lamin A/C binding protein LAP2alpha is required for nuclear anchorage of retinoblastoma protein. Mol. Biol. Cell. December 2002, 13 (12): 4401–13. PMC 138642 . PMID 12475961. doi:10.1091/mbc.E02-07-0450.
^ Dechat T, Korbei B, Vaughan OA, Vlcek S, Hutchison CJ, Foisner R. Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins. J. Cell. Sci. October 2000, 113 (19): 3473–84. PMID 10984438.
^ Dreuillet C, Tillit J, Kress M, Ernoult-Lange M. In vivo and in vitro interaction between human transcription factor MOK2 and nuclear lamin A/C. Nucleic Acids Res. November 2002, 30 (21): 4634–42. PMC 135794 . PMID 12409453. doi:10.1093/nar/gkf587.
^ PMID 23217256（PMID 23217256）
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延伸阅读

Gruenbaum Y, Wilson KL, Harel A; et al. Review: nuclear lamins--structural proteins with fundamental functions.. J. Struct. Biol. 2000, 129 (2–3): 313–23. PMID 10806082. doi:10.1006/jsbi.2000.4216.
Worman HJ, Courvalin JC. The inner nuclear membrane. J. Membr. Biol. 2000, 177 (1): 1–11. PMID 10960149. doi:10.1007/s002320001096.
Burke B, Mounkes LC, Stewart CL. The nuclear envelope in muscular dystrophy and cardiovascular diseases. Traffic. 2002, 2 (10): 675–83. PMID 11576443. doi:10.1034/j.1600-0854.2001.21001.x.
Mounkes LC, Burke B, Stewart CL. The A-type lamins: nuclear structural proteins as a focus for muscular dystrophy and cardiovascular diseases. Trends Cardiovasc. Med. 2001, 11 (7): 280–5. PMID 11709282. doi:10.1016/S1050-1738(01)00126-8.
Vigouroux C, Magré J, Desbois-Mouthon C; et al. [Major insulin resistance syndromes: clinical and physiopathological aspects]. J. Soc. Biol. 2002, 195 (3): 249–57. PMID 11833462.
Helbling-Leclerc A, Bonne G, Schwartz K. Emery-Dreifuss muscular dystrophy. Eur. J. Hum. Genet. 2002, 10 (3): 157–61. PMID 11973618. doi:10.1038/sj.ejhg.5200744.
Burke B, Stewart CL. Life at the edge: the nuclear envelope and human disease. Nat. Rev. Mol. Cell Biol. 2002, 3 (8): 575–85. PMID 12154369. doi:10.1038/nrm879.
Novelli G, D'Apice MR. The strange case of the "lumper" lamin A/C gene and human premature ageing. Trends in molecular medicine. 2004, 9 (9): 370–5. PMID 13129702. doi:10.1016/S1471-4914(03)00162-X.
Pasotti M, Repetto A, Pisani A, Arbustini E. [Diseases associated with lamin A/C gene defects: what the clinical cardiologist ought to know]. Italian heart journal. Supplement : official journal of the Italian Federation of Cardiology. 2004, 5 (2): 98–111. PMID 15080529.
Al-Shali KZ, Hegele RA. Laminopathies and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2005, 24 (9): 1591–5. PMID 15205220. doi:10.1161/01.ATV.0000136392.59656.8b.
Garg A, Cogulu O, Ozkinay F; et al. A novel homozygous Ala529Val LMNA mutation in Turkish patients with mandibuloacral dysplasia. J. Clin. Endocrinol. Metab. 2005, 90 (9): 5259–64. PMID 15998779. doi:10.1210/jc.2004-2560.
Lees-Miller SP. Dysfunction of lamin A triggers a DNA damage response and cellular senescence. DNA Repair (Amst.). 2006, 5 (2): 286–9. PMID 16344005. doi:10.1016/j.dnarep.2005.10.007.
Donadille B, Lascols O, Capeau J, Vigouroux C. Etiological investigations in apparent type 2 diabetes: when to search for lamin A/C mutations?. Diabetes Metab. 2006, 31 (6): 527–32. PMID 16357800. doi:10.1016/S1262-3636(07)70227-6.
Young SG, Meta M, Yang SH, Fong LG. Prelamin A farnesylation and progeroid syndromes. J. Biol. Chem. 2007, 281 (52): 39741–5. PMID 17090536. doi:10.1074/jbc.R600033200.
Halaschek-Wiener J, Brooks-Wilson A. Progeria of stem cells: stem cell exhaustion in Hutchinson-Gilford progeria syndrome. J. Gerontol. A Biol. Sci. Med. Sci. 2007, 62 (1): 3–8. PMID 17301031. doi:10.1093/gerona/62.1.3.
Mazereeuw-Hautier J, Wilson LC, Mohammed S; et al. Hutchinson-Gilford progeria syndrome: clinical findings in three patients carrying the G608G mutation in LMNA and review of the literature. Br. J. Dermatol. 2007, 156 (6): 1308–14. PMID 17459035. doi:10.1111/j.1365-2133.2007.07897.x.
Sliwińska MA. [The role of lamins and mutations of LMNA gene in physiological and premature aging]. Postepy Biochem. 2007, 53 (1): 46–52. PMID 17718387.
Genschel J, Schmidt HH. Mutations in the LMNA gene encoding lamin A/C. Hum. Mutat. December 2000, 16 (6): 451–9. PMID 11102973. doi:10.1002/1098-1004(200012)16:6<451::AID-HUMU1>3.0.CO;2-9.
Scaffidi P, Misteli T. Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat Med. April 2005, 11 (4): 440–5. PMC 1351119 . PMID 15750600. doi:10.1038/nm1204.

外部链接

Bird, Thomas D. Charcot-Marie-Tooth Neuropathy Type 2. 30 January 2014. PMID 20301462. NBK1285. In Pagon RA, Bird TD, Dolan CR; et al (编). GeneReviews™ [Internet]. Seattle WA: University of Washington, Seattle. 1993–. 请检查|date=中的日期值 (帮助)
Sparks, Susan; Quijano-Roy, Susana; Harper, Amy; Rutkowski, Anne; Gordon, Erynn; Hoffman, Eric P; Pegoraro, Elena. Congenital Muscular Dystrophy Overview. 23 August 2012. PMID 20301468. NBK1291. In GeneReviews
Hershberger, Ray E; Morales, Ana. LMNA-Related Dilated Cardiomyopathy. 19 September 2013. PMID 20301717. NBK1674. In GeneReviews
- OMIM Cardiomyopathy, Dilated, 1A; CMD1A -115200
- OMIM LAMIN A/C; LMNA -150330
Pegoraro, Elena; Hoffman, Eric P. Limb-Girdle Muscular Dystrophy Overview. 30 August 2012. PMID 20301582. NBK1408. In GeneReviews GeneReviews/NCBI/NIH/UW entry on
Bonne, Gisèle; Leturcq, France; Yaou, Rabah Ben. Emery-Dreifuss Muscular Dystrophy. 17 January 2013. PMID 20301609. NBK1436. In GeneReviews
Gordon, Leslie B; Brown, W Ted; Collins, Francis S. Hutchinson-Gilford Progeria Syndrome. 6 January 2011. PMID 20301300. NBK1121. In GeneReviews
Corchado, Johnny Cruz; Smith, Richard JH. Dense Deposit Disease/Membranoproliferative Glomerulonephritis Type II. 19 May 2011. PMID 20301598. NBK1425. In GeneReviews

醫學主題詞表（MeSH）：LMNA+protein,+human
LOVD mutation database: LMNA

[pmid8511676-1] Kamat AK, Rocchi M, Smith DI, Miller OJ. Lamin A/C gene and a related sequence map to human chromosomes 1q12.1-q23 and 10. Somat. Cell Mol. Genet. March 1993, 19 (2): 203–8. PMID 8511676. doi:10.1007/BF01233534.

[pmid8838815-2] Wydner KL, McNeil JA, Lin F, Worman HJ, Lawrence JB. Chromosomal assignment of human nuclear envelope protein genes LMNA, LMNB1, and LBR by fluorescence in situ hybridization. Genomics. March 1996, 32 (3): 474–8. PMID 8838815. doi:10.1006/geno.1996.0146.

[pmid19379495-3] Coutinho HD, Falcão-Silva VS, Gonçalves GF, da Nóbrega RB. Molecular ageing in progeroid syndromes: Hutchinson-Gilford progeria syndrome as a model. Immun Ageing. 2009, 6: 4. PMC 2674425 . PMID 19379495. doi:10.1186/1742-4933-6-4.

[4] Entrez Gene: LMNA lamin A/C.

[pmid17139325-5] Capell BC, Collins FS. Human laminopathies: nuclei gone genetically awry. Nat. Rev. Genet. December 2006, 7 (12): 940–52. PMID 17139325. doi:10.1038/nrg1906.

[pmid16965317-6] Rankin J, Ellard S. The laminopathies: a clinical review. Clin. Genet. October 2006, 70 (4): 261–74. PMID 16965317. doi:10.1111/j.1399-0004.2006.00677.x.

[pmid10727209-7] Tang K, Finley RL, Nie D, Honn KV. Identification of 12-lipoxygenase interaction with cellular proteins by yeast two-hybrid screening. Biochemistry. March 2000, 39 (12): 3185–91. PMID 10727209. doi:10.1021/bi992664v.

[pmid12755701-8] Wilkinson FL, Holaska JM, Zhang Z, Sharma A, Manilal S, Holt I, Stamm S, Wilson KL, Morris GE. Emerin interacts in vitro with the splicing-associated factor, YT521-B. Eur. J. Biochem. June 2003, 270 (11): 2459–66. PMID 12755701. doi:10.1046/j.1432-1033.2003.03617.x.

[pmid12670476-9] Lattanzi G, Cenni V, Marmiroli S, Capanni C, Mattioli E, Merlini L, Squarzoni S, Maraldi NM. Association of emerin with nuclear and cytoplasmic actin is regulated in differentiating myoblasts. Biochem. Biophys. Res. Commun. April 2003, 303 (3): 764–70. PMID 12670476. doi:10.1016/S0006-291X(03)00415-7.

[pmid11173535-10] Sakaki M, Koike H, Takahashi N, Sasagawa N, Tomioka S, Arahata K, Ishiura S. Interaction between emerin and nuclear lamins. J. Biochem. February 2001, 129 (2): 321–7. PMID 11173535. doi:10.1093/oxfordjournals.jbchem.a002860.

[pmid10673356-11] Clements L, Manilal S, Love DR, Morris GE. Direct interaction between emerin and lamin A. Biochem. Biophys. Res. Commun. January 2000, 267 (3): 709–14. PMID 10673356. doi:10.1006/bbrc.1999.2023.

[pmid10514485-12] Barton RM, Worman HJ. Prenylated prelamin A interacts with Narf, a novel nuclear protein. J. Biol. Chem. October 1999, 274 (42): 30008–18. PMID 10514485. doi:10.1074/jbc.274.42.30008.

[pmid11929849-13] Lloyd DJ, Trembath RC, Shackleton S. A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies. Hum. Mol. Genet. April 2002, 11 (7): 769–77. PMID 11929849. doi:10.1093/hmg/11.7.769.

[pmid12475961-14] Markiewicz E, Dechat T, Foisner R, Quinlan RA, Hutchison CJ. Lamin A/C binding protein LAP2alpha is required for nuclear anchorage of retinoblastoma protein. Mol. Biol. Cell. December 2002, 13 (12): 4401–13. PMC 138642 . PMID 12475961. doi:10.1091/mbc.E02-07-0450.

[pmid10984438-15] Dechat T, Korbei B, Vaughan OA, Vlcek S, Hutchison CJ, Foisner R. Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins. J. Cell. Sci. October 2000, 113 (19): 3473–84. PMID 10984438.

[pmid12409453-16] Dreuillet C, Tillit J, Kress M, Ernoult-Lange M. In vivo and in vitro interaction between human transcription factor MOK2 and nuclear lamin A/C. Nucleic Acids Res. November 2002, 30 (21): 4634–42. PMC 135794 . PMID 12409453. doi:10.1093/nar/gkf587.

[pmid23217256-17] PMID 23217256（PMID 23217256）
本引用來源將由机器人自動扩充。您可以检查英文对应模板或手動擴充

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