LMNA

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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
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英语ChEMBL: 1293235 GeneCards: LMNA Gene
RNA表达模式
PBB GE LMNA 203411 s at tn.png
PBB GE LMNA 212086 x at tn.png
PBB GE LMNA 214213 x at tn.png
更多表达数据
直系同源体
物种 人类 小鼠
Entrez 4000 16905
Ensembl ENSG00000160789 ENSMUSG00000028063
UniProt P02545 P48678
mRNA序列 NM_001257374 NM_001002011
蛋白序列 NP_001244303 NP_001002011
基因位置 Chr 1:
156.05 – 156.11 Mb
Chr 3:
88.48 – 88.51 Mb
PubMed查询 [1] [2]

核纤层蛋白 A/C英语: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[编辑]

Biogenesis of lamin A in normal cells and the failure to generate mature lamin A in HGPS. In the setting of ZMPSTE24 deficiency, the final step of lamin processing does not occur, resulting in an accumulation of farnesyl-prelamin A. In HGPS, a 50-amino acid deletion in prelamin A (amino acids 607–656) removes the site for the second endoproteolytic cleavage. Consequently, no mature lamin A is formed, and a farnesylated mutant prelamin A (progerin) accumulates in cells. Coutinho et al. Immunity & Ageing 2009.[3]

核纖層是真核生物细胞核中附于内核膜英语inner nuclear membrane内侧的网络片层结构。其核纤层蛋白家族在进化中高度保守。在有絲分裂过程中,核纤层蛋白磷酸化,核纖層解聚(这一过程是可逆的)。Lamin蛋白質被認為與細胞核的穩定性、染色質的結構與基因的表達有關. 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[编辑]

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[编辑]

LMNA has been shown to interact with:


参考文献[编辑]

  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  17. ^ PMID 23217256PubMed
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