LMNA

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。

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
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]
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功能

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]

核纤层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。在有丝分裂过程中，核纤层蛋白磷酸化，核纤层解聚（这一过程是可逆的）。Lamin蛋白质被认为与细胞核的稳定性、染色质的结构与基因的表达有关. 脊椎动物的核纤层蛋白包含A和B两种形式。人类Lamin A/C基因透过选择性剪接可以产生出三种A型异构体。^[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]

与其他蛋白或基因的交互作用

LMNA has been shown to interact with:

• ALOX12^[7]
• EMD^{[8][9][10][11]}
• NARF^[12]
• SREBF1^[13]
• TMPO^[14][15]
• ZNF239^[16]
• SIRT1^[17]