MRP3, a new ATP-binding cassette protein localized to the canalicular domain of the hepatocyte.
MRP3, a new ATP-binding cassette protein localized to the canalicular domain of the hepatocyte.
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MRP3，一种定位于肝细胞小管结构域的新 ATP 结合盒蛋白。
DOI：
10.1152/ajpgi.1999.276.6.g1493
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Arias,IM
中科院分区：
文献类型：
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作者：
Ortiz,DF;Li,S;Iyer,R;Zhang,X;Novikoff,P;Arias,IM
肝脏的胆汁分泌在很大程度上是由atp结合盒（ABC）型蛋白驱动的，这些蛋白位于管膜上，影响胆汁酸、磷脂和非胆汁酸有机阴离子的atp依赖性运输。基于膜拓扑结构和序列一致性，管状abc型蛋白可以分为两个亚家族：MDR1、MDR3和SPGP类似于多药耐药（MDR） p -糖蛋白，而MRP2在结构和序列上与多药耐药蛋白MRP1相似，并且运输类似的底物。我们现在报道了从大鼠肝脏中分离到的rMRP3基因，该基因编码一个长度为1522个氨基酸的蛋白质，与MRP1和MRP2具有广泛的序列相似性。Northern blot分析显示，Sprague-Dawley大鼠的肺和肠以及卫塞高胆红素血症大鼠和TR -突变大鼠的肝脏中均有rMRP3表达，而MRP2表达缺失。rMRP3的表达在出生后不久和梗阻性胆汁淤积时也会短暂地在肝脏中被诱导。MRP3抗体识别190-200 kDa的多肽，经内糖苷酶处理后，其大小减少到155-165 kDa。免疫印迹分析和免疫共聚焦显微镜显示rMRP3存在于小管膜中，提示其可能在胆汁形成中起作用。
Bile secretion in liver is driven in large part by ATP-binding cassette (ABC)-type proteins that reside in the canalicular membrane and effect ATP-dependent transport of bile acids, phospholipids, and non-bile acid organic anions. Canalicular ABC-type proteins can be classified into two subfamilies based on membrane topology and sequence identity: MDR1, MDR3, and SPGP resemble the multidrug resistance (MDR) P-glycoprotein, whereas MRP2 is similar in structure and sequence to the multidrug resistance protein MRP1 and transports similar substrates. We now report the isolation of the rMRP3 gene from rat liver, which codes for a protein 1522 amino acids in length that exhibits extensive sequence similarity with MRP1 and MRP2. Northern blot analyses indicate that rMRP3 is expressed in lung and intestine of Sprague-Dawley rats as well as in liver of Eisai hyperbilirubinemic rats and TR−mutant rats, which are deficient in MRP2 expression. rMRP3 expression is also transiently induced in liver shortly after birth and during obstructive cholestasis. Antibodies raised against MRP3 recognize a polypeptide of 190–200 kDa, which is reduced in size to 155–165 kDa after treatment with endoglycosidases. Immunoblot analysis and immunoconfocal microscopy indicate that rMRP3 is present in the canalicular membrane, suggesting that it may play a role in bile formation.