简介

Apolipoprotein A-I载脂蛋白A1PDB rendering based on 1av1.有效结构PDB直系同源检索：PDBe, RCSBPDB查询代码列表1*1, 1GW3, 1GW4, 1ODP, 1ODQ, 1ODR, 2A01, 3J00, 3K2S, 3R2P标识代号APOA1; MGC117399扩展标识遗传学：107680 鼠基因：88049 同源基因：47900 ChEMBL: 5984 GeneCards: APOA1 Gene基因本体论描述 分子功能· beta-amyloid binding · protein binding · phospholipid binding · phospholipid transporter activity · high-density lipoprotein particle binding · cholesterol binding · cholesterol transporter activity · enzyme binding · apolipoprotein receptor binding · apolipoprotein A-I receptor binding · identical protein binding · lipase inhibitor activity · phosphatidylcholine-sterol O-acyltransferase activator activity · high-density lipoprotein particle receptor binding 细胞成分· extracellular region · extracellular space · nucleus · early endosome · endopla*ic reticulum lumen · cytosol · pla*a membrane · endocytic vesicle · cytopla*ic vesicle · very-low-density lipoprotein particle · high-density lipoprotein particle · spherical high-density lipoprotein particle · secretory granule lumen 生物过程· retinoid metabolic process · regulation of protein phosphorylation · endothelial cell proliferation · platelet degranulation · negative regulation of cytokine secretion involved in immune response · lipid metabolic process · phosphatidylcholine biosynthetic process · cholesterol biosynthetic process · G-protein coupled receptor signaling pathway · response to nutrient · blood coagulation · phototransduction, visible light · cholesterol metabolic process · glucocorticoid metabolic process · negative regulation of tumor necrosis factor-mediated signaling pathway · positive regulation of cholesterol esterification · negative regulation of very-low-density lipoprotein particle remodeling · peripheral nervous system axon regeneration · protein oxidation · peptidyl-methionine modification · lipid storage · platelet activation · regulation of intestinal cholesterol absorption · cholesterol transport · adrenal gland development · organ regeneration · regulation of Cdc42 protein signal transduction · cholesterol efflux · phospholipid efflux · negative regulation of heterotypic cell-cell adhesion · high-density lipoprotein particle remodeling · high-density lipoprotein particle assembly · high-density lipoprotein particle clearance · lipoprotein metabolic process · lipoprotein biosynthetic process · response to drug · cholesterol homeostasis · blood vessel endothelial cell migration · response to estrogen stimulus · reverse cholesterol transport · cellular lipid metabolic process · *all molecule metabolic process · negative regulation of interleukin-1 beta secretion · negative regulation of inflam*tory response · protein stabilization · positive regulation of hydrolase activity · positive regulation of transferase activity · tran*embrane transport · phospholipid homeostasis · negative regulation of lipase activity · negative regulation of cell adhesion molecule production · negative regulation of response to cytokine stimulus · triglyceride homeostasis · cholesterol importSources: Amigo / QuickGORNA表达模式更多表达数据直系同源体物种人类小鼠Entrez33511806EnsemblENSG00000118137EN*USG00000032083UniProtP02*7Q00623mRNA序列NM_000039NM_009692蛋白序列NP_000030NP_033822基因位置Chr 11:116.71 – 116.71 MbChr 9:46.23 – 46.23 MbPubMed查询查论编载脂蛋白A1（英语：Apolipoprotein A1，简称ApoA1）为附着于高密度脂蛋白（HDL）及乳靡小球上的载脂蛋白，基因编码为“APOA1”。载脂蛋白A1可以活化卵磷脂-胆固醇酰基转移酶（英语：Lecithin—cholesterol acyltransferase）（Lecithin Cholesterol Acyltransferase，LCAT）；当高密度脂蛋白运送组织中多余的胆固醇回到肝脏细胞中时，载脂蛋白A1同时也可作为高密度脂蛋白的配体，在脂质代谢（英语：lipid metaboli*）中扮演重要角色。研究指出，APOA1的mRNA是由反义RNA转译出的内源性蛋白质所调控。

结构

APOA1基因位于第11对染色体上（11q23-q24），该基因包含4个外显子。载脂蛋白A1的质量为45.4 kDa ，含有 396 个氨基酸；质谱分析可观察到蛋白质由21个胜肽片段组成。

功能

载脂蛋白A1（ApoA1）为构成血浆中高密度脂蛋白（HDL）蛋白质部分的主要成分。小肠肠道细胞所分泌的乳糜微粒中虽然也含有载脂蛋白A1，但在血流中很快就会被转为HDL。ApoA1可促进将周边组织脂质及胆固醇回收至肝脏，并借由胆管分泌至小肠。另外该蛋白也是卵磷脂-胆固醇酰基转移酶（英语：Lecithin—cholesterol acyltransferase）（LCAT）的辅因子，制造了血浆中大多数的胆固醇脂（英语：cholesteryl esters）。ApoA1同时也是前列环素（PGI2）的稳定因子，因此也具有抗凝血的作用。如果编码该蛋白的基因有缺陷，会导致个体体内缺乏HDL，导致包含Tangier disease（英语：Tangier disease）在内的症状，以及非神经性全身类淀粉变性。

由于ApoA1在体内脂质代谢的角色相当重要，因此常被视为预测个体冠心病风险的生物标记。有研究发现“apoB-100/apoA1”的比值预测心肌梗塞的效果比任何其他脂质标记更有效果。ApoA1可利用ELISA或nephelometry（英语：nephelometry）检验。

临床意义

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Activity associated with high HDL-C and protection from heart disease

As a *jor component of the high-density lipoprotein complex (protective *fat removal* particles), apo A1 helps to clear fats, including cholesterol, from white blood cells within artery walls, *king the WBCs less likely to become fat overloaded, transform into foam cells, * and contribute to progressive athero*（英语：athero*）. Five of nine men found to carry a mutation (E1*X) who were at least 35 years of age had developed pre*ture coronary artery disease.One of four mutants of apo A1 is present in roughly 0.3% of the Japanese population, but is found in 6% of those with low HDL cholesterol levels.

ApoA-1 Milano（英语：ApoA-1 Milano） is a naturally occurring mutant of apo A1, found in a few families in Limone sul Garda, Italy, and, by genetic + church record family tree detective work, traced to a single individual in the 14th century. Described in 1980, it was the first known molecular abnor*lity of apolipoproteins.Paradoxically, carriers of this mutation have very low HDL-C (HDL-Cholesterol) levels, but no increase in the risk of heart disease, often living to age 100 or older. This unusual observation was what lead Italian investigators to track down what was going on and lead to the discovery of apo A1 Milano (the city, Milano, ~160 km away, in which the researcher's lab was located). Biochemically, apo A1 contains an extra cysteine bridge, causing it to exist as a homodimer or as a heterodimer with apo A-II. However, the enhanced cardioprotective activity of this mutant (which likely depends on fat & cholesterol efflux) cannot easily be replicated by other cysteine mutants.

Recombinant apo A1 Milano dimers formulated into liposomes can reduce athero*（英语：athero*）s in ani*l models by up to 30%.Apo A1 Milano has also been shown in *all clinical trials to have a statistically significant effect in reducing (reversing) plaque build-up on arterial walls.

In hu*n trials the reversal of plaque build-up was measured over the course of five weeks.

Novel Haplotypes within apolipoprotein AI-CIII-AIV gene cluster

Lately, two novel susceptibility haplotypes i.e. P2-S2-X1 and P1-S2-X1 have been discovered in ApoAI-CIII-AIV gene cluster on chromosome 11q23, which confer approxi*tely threefold higher risk of coronary heart disease in nor*las well as in the patients having non-insulin diabetes mellitus.

Role in other diseases

A G/A polymorphi* in the promoter of the apo A1 gene has been associated with the age at which patients presented with Alzheimer disease.Protection from Alzheimer's disease by apo A1 *y rely on a synergistic interaction with alpha-tocopherol（英语：alpha-tocopherol）.Amyloid deposited in the knee following surgery consists largely of apo A1 secreted from chondrocytes (cartilage cells).A wide variety of amyloidosis symptoms are associated with rare Apo A1 mutants.

Apo A-I binds to lipopolysaccharide or endotoxin, and has a *jor role in the anti-endotoxin function of HDL.

In one study, a decrease in apo A1 levels was detected in schizophrenia patients' CSF, brain and peripheral tissues.

Epistatic impact of apo A1

Apolipoprotein A1 and APOE interact epistatically to modulate triglyceride levels in coronary heart disease patients. Individually, neither apo A1 nor apo E was found to be associated with triglyceride (TG) levels, but pairwise epistasis (additive x additive model) explored their significant synergistic contributions with raised TG levels (P<0.01).

Factors affecting apo A1 activity

Apo A1 production is decreased by calcitriol, and increased by a drug that antagonizes it.

Exercise or statin treatment *y cause an increase in HDL-C levels by inducing apo A1 production, but this depends on the G/A promoter polymorphi*.

交互作用

载脂蛋白A1可与下列蛋白产生交互作用：

ABCA1（英语：ABCA1）

GPLD1（英语：GPLD1）and

PLTP（英语：PLTP）

Potential binding partners

Apolipoprotein A1 binding precursor, a relative of APOA-1 abbreviated APOA1BP（英语：APOA1BP）, has a predicted biochemical interaction with Carbohydrate Kinase Do*in Containing Protein（英语：CARKD）. The relationship between these two proteins is substantiated by cooccurance across genomes and coexpression.The ortholog of CARKD in E. coli contains a do*in not present in any eukaryotic ortholog. This do*in has a high sequence identity to APOA1BP. CARKD is a protein of unknown function, and the biochemical basis for this interaction is unknown.

交互作用途径

点击基因、蛋白质和代谢产物的链接访问对应的介绍条目。

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^ 这个相互作用途径可以在WikiPathways上编辑: Statin_Pathway_WP430.