SLC46A1 Q96NT5

质子偶联叶酸转运蛋白 (HsPCFT) (hPCFT) (血红素载体蛋白 1) (PCFT/HCP1) (溶质载体家族46成员1)

功能描述

质子偶联叶酸同向转运蛋白，利用H(+)梯度作为驱动力介导叶酸吸收 (PubMed:17129779, PubMed:17446347, PubMed:17475902, PubMed:19389703, PubMed:19762432, PubMed:25504888, PubMed:29344585, PubMed:30858177, PubMed:31494288, PubMed:31792273, PubMed:32893190, PubMed:34619546)。参与近端空肠刷状缘膜处的叶酸肠道吸收，以及跨越脉络丛从血液到脑脊液的转运 (PubMed:17129779, PubMed:17446347, PubMed:17475902, PubMed:19389703, PubMed:25504888, PubMed:29344585, PubMed:30858177, PubMed:31494288, PubMed:32893190)。通过交替的外向开放和内向开放构象状态在酸性pH下发挥功能 (PubMed:32893190, PubMed:34040256)。外向开放状态下残基的质子化使蛋白准备好进行转运 (PubMed:34040256)。叶酸的结合促进盐桥网络断裂及随后的胞外门关闭，导致内向开放状态并释放质子和叶酸 (PubMed:34040256)。也能够转运抗叶酸药物，如甲氨蝶呤和培美曲塞，这些是治疗癌症和自身免疫性疾病的成熟药物 (PubMed:18524888, PubMed:19762432, PubMed:22345511, PubMed:25608532, PubMed:28802835, PubMed:29326243, PubMed:34040256, PubMed:34619546)。作为酸化内体中叶酸的输出途径，参与FOLR1介导的内吞作用 (PubMed:19074442)。也作为低亲和力、不依赖pH的血红素载体蛋白，构成肠道中血红素的主要输入者 (PubMed:17156779)。在视网膜和视网膜色素上皮、海马神经元、肝细胞和肾上皮细胞中输入血红素 (PubMed:32621820)。因此，参与血红素的运输并增加细胞内铁含量 (PubMed:32621820)。 {ECO:0000269|PubMed:17129779, ECO:0000269|PubMed:17156779, ECO:0000269|PubMed:17446347, ECO:0000269|PubMed:17475902, ECO:0000269|PubMed:18524888, ECO:0000269|PubMed:19074442, ECO:0000269|PubMed:19389703, ECO:0000269|PubMed:19762432, ECO:0000269|PubMed:22345511, ECO:0000269|PubMed:25504888, ECO:0000269|PubMed:25608532, ECO:0000269|PubMed:28802835, ECO:0000269|PubMed:29326243, ECO:0000269|PubMed:29344585, ECO:0000269|PubMed:30858177, ECO:0000269|PubMed:31494288, ECO:0000269|PubMed:31792273, ECO:0000269|PubMed:32621820, ECO:0000269|PubMed:32893190, ECO:0000269|PubMed:34040256, ECO:0000269|PubMed:34619546}.; FUNCTION: [Isoform 2]: 无活性异构体，无法介导质子偶联的叶酸转运。 {ECO:0000269|PubMed:17129779}.

组织特异性

Expressed at highest level in the upper half of the small intestine (duodenum and jejunum), expression decreases downwardly in the subsequent quarter and is undetectable in the last quarter (the lowest ileum) (PubMed:17129779, PubMed:19762432). Also expressed in kidney, liver, placenta, spleen, retina and retinal pigment epithelium (PubMed:17129779, PubMed:17335806). Lower levels found in testis (PubMed:17129779). Very low levels in brain, lung, stomach, heart and muscle (PubMed:17129779).

亚细胞定位

Cell membrane