Molecular cloning, functional expression and chromosomal localization of a cDNA encoding a human Na+/nucleoside cotransporter (hCNT2) selective for purine nucleosides and uridine.
Molecular cloning, functional expression and chromosomal localization of a cDNA encoding a human Na+/nucleoside cotransporter (hCNT2) selective for purine nucleosides and uridine.
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编码对嘌呤核苷和尿苷具有选择性的人钠/核苷协同转运蛋白 (hCNT2) 的 cDNA 的分子克隆、功能表达和染色体定位。
作者：
M. Ritzel;S. Yao;A. Ng;J. Mackey;C. Cass;J. Young
在哺乳动物细胞中，两种涉及腺苷和尿苷转运的Na（+）依赖性核苷转运蛋白在功能上基于底物特异性而区分：CNT 1选择性地转运嘧啶核苷，但也转运腺苷; CNT 2（也称为SPNT）选择性地转运嘌呤核苷，但也转运尿苷。这两种蛋白都属于一个基因家族，该家族包括大肠杆菌的NupC质子/核苷同向转运体。杆菌编码CNT家族成员的cDNA已从大鼠组织（空肠、脑、肝脏; rCNT 1和rCNT 2/SPNT）以及最近的人肾脏（hCNT 1和hSPNT 1）中分离出来。在这里，CNT 2/SPNT型转运蛋白从人类小肠的分子克隆和功能特性的描述。编码的658个残基的蛋白质（hCNT 2的命名）具有相同的预测的氨基酸序列作为人类肾脏hSPNT 1，除了在残基75（Arg取代丝氨酸）的多态性，并分别为83%和72%相同的rCNT 2和hCNT 1。hCNT 2和rCNT 2之间的序列差异在N-末端最大。在非洲爪蟾卵母细胞中，重组hCNT 2表现出Na（+）依赖性核苷转运蛋白的功能特征，对腺苷、其他嘌呤核苷和尿苷具有选择性（腺苷和尿苷K（m）app值分别为8和40 μ M）。在肾脏和小肠中发现hCNT 2转录物，但与rCNT 2不同，在肝脏中未检测到hCNT 2转录物。脱氧腺苷在人体中经历肾净分泌，比腺苷更不易转运。hCNT 2还介导小但显著的抗病毒嘌呤核苷类似物2 '，3'-二脱氧肌苷的通量。因此，hCNT 2可能参与嘌呤核苷（包括腺苷）、尿苷和嘌呤核苷药物的肠吸收和肾处理。编码hCNT 2的基因定位于染色体15 q15。
Two Na(+)-dependent nucleoside transporters implicated in adenosine and uridine transport in mammalian cells are distinguished functionally on the basis of substrate specificity: CNT1 is selective for pyrimidine nucleosides but also transports adenosine; CNT2 (also termed SPNT) is selective for purine nucleosides but also transports uridine. Both proteins belong to a gene family that includes the NupC proton/nucleoside symporter of E. coli. cDNAs encoding members of the CNT family have been isolated from rat tissues (jejunum, brain, liver; rCNT1 and rCNT2/SPNT) and, most recently, human kidney (hCNT1 and hSPNT1). Here, the molecular cloning and functional characterization of a CNT2/SPNT-type transporter from human small intestine are described. The encoded 658-residue protein (hCNT2 in the nomenclature) had the same predicted amino acid sequence as human kidney hSPNT1, except for a polymorphism at residue 75 (Arg substituted by Ser), and was 83 and 72% identical to rCNT2 and hCNT1, respectively. Sequence differences between hCNT2 and rCNT2 were greatest at the N-terminus. In Xenopus oocytes, recombinant hCNT2 exhibited the functional characteristics of a Na(+)-dependent nucleoside transporter with selectivity for adenosine, other purine nucleosides and uridine (adenosine and uridine K(m) app values 8 and 40 microM, respectively). hCNT2 transcripts were found in kidney and small intestine but, unlike rCNT2, were not detected in liver. Deoxyadenosine, which undergoes net renal secretion in humans, was less readily transported than adenosine. hCNT2 also mediated small, but significant, fluxes of the antiviral purine nucleoside analogue 2',3'-dideoxyinosine. hCNT2 is, therefore potentially involved in both the intestinal absorption and renal handling of purine nucleosides (including adenosine), uridine and purine nucleoside drugs. The gene encoding hCNT2 was mapped to chromosome 15q15.
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DOI：
10.1152/ajprenal.1997.273.6.f1058
发表时间：
1997-12-01
影响因子：
4.2
作者：
Wang, J;Su, SF;Giacomini, KM
通讯作者：
Giacomini, KM
核苷转运蛋白在功能上与大鼠肝小管膜中的核酸外切酶相关。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Che,M;Nishida,T;Gatmaitan,Z;Arias,IM
通讯作者：
Arias,IM
L1210 鼠白血病细胞中的核苷转运。
DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Crawford,CR;Ng,CY;Noel,LD;Belt,JA
通讯作者：
Belt,JA
人肠刷状缘膜中钠依赖性核苷转运。
DOI：
10.1152/ajpgi.1997.272.6.g1314
发表时间：
1997
期刊：
The American journal of physiology
影响因子：
--
作者：
Patil,SD;Unadkat,JD
通讯作者：
Unadkat,JD
人肾钠核苷协同转运蛋白在非洲爪蟾卵母细胞中的表达。
影响因子：
5.8
作者：
Gutierrez,MM;Giacomini,KM
通讯作者：
Giacomini,KM