SLC15A4 Q8N697

溶质载体家族15成员4 (肽转运蛋白4) (肽/组氨酸转运蛋白1) (hPHT1)

功能描述

质子偶联氨基酸转运蛋白，介导L-组氨酸和部分二肽及三肽从溶酶体内部跨膜转运至细胞质，并在先天免疫反应中发挥关键作用 (PubMed:16289537, PubMed:25238095, PubMed:29224352, PubMed:39719710)。优先结合第一位为碱性残基且第二位为疏水残基的短肽 (PubMed:39719710)。能够转运多种二肽和三肽，包括肌肽和部分肽聚糖 (PubMed:29224352, PubMed:31073693)。转运活性依赖于pH值，并在酸性溶酶体环境中达到最大活性 (By similarity)。参与通过toll样受体 (TLRs) 和NOD样受体 (NLRs) 检测微生物病原体，可能通过介导细菌肽聚糖跨内溶酶体膜转运实现：催化特定细菌肽聚糖的转运，例如NOD2配体胞壁酰二肽 (MDP) 和NOD1配体L-丙氨酰-γ-D-谷氨酰-内消旋-2,6-二氨基庚二酸 (tri-DAP) (PubMed:25238095, PubMed:29224352)。浆细胞样树突状细胞 (pDCs) 中TLR7、TLR8和TLR9介导的I型干扰素 (IFN-I) 产生所必需的 (PubMed:25238095)。独立于其转运活性，还促进先天免疫接头蛋白TASL在TLR7、TLR8和TLR9下游募集至内溶酶体：TASL募集导致IRF5的特异性募集和激活 (PubMed:32433612, PubMed:39719710)。响应TLR9刺激的同种型类别转换为IgG2c同种型所必需的 (By similarity)。通过限制肥大细胞功能和炎症反应，维持肥大细胞分泌颗粒稳态所必需的 (By similarity)。 {ECO:0000250|UniProtKB:O09014, ECO:0000250|UniProtKB:Q91W98, ECO:0000269|PubMed:16289537, ECO:0000269|PubMed:25238095, ECO:0000269|PubMed:29224352, ECO:0000269|PubMed:31073693, ECO:0000269|PubMed:32433612, ECO:0000269|PubMed:39719710}。

组织特异性

Highly expressed in skeletal muscle. Moderately expressed in kidney, liver, and heart. Weakly expressed in colon and brain. Expressed in low levels throughout the gastrointestinal tract and in Caco-2 cells. Expressed in retinal fragment epithelium (RPE) and neural retina. Expressed in small intestine, stomach, duodenum, jejunum, ileum and colon.

亚细胞定位

Lysosome membrane