ACKR2 O00590

非典型趋化因子受体2 (C-C趋化因子受体D6) (趋化因子受体CCR-10) (趋化因子受体CCR-9) (趋化因子结合蛋白2) (趋化因子结合蛋白D6)

功能描述

非典型趋化因子受体，通过高亲和力趋化因子结合控制趋化因子的水平和定位，该结合与经典的配体驱动信号转导级联反应解偶联，从而导致趋化因子隔离、降解或跨细胞转运 (PubMed:18201974, PubMed:20373092, PubMed:23479571)。也被称为内吞受体（内化受体）或趋化因子清除受体或趋化因子诱饵受体 (PubMed:18201974, PubMed:20373092, PubMed:23479571)。作为趋化因子的受体，包括 CCL2, CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL22, CCL23, CCL24, SCYA2/MCP-1, SCY3/MIP-1-alpha, SCYA5/RANTES 和 SCYA7/MCP-3 (PubMed:18201974, PubMed:20373092, PubMed:23479571)。在活性配体刺激下，激活 beta-arrestin 1 (ARRB1) 依赖性、G 蛋白非依赖性信号通路，通过 RAC1-PAK1-LIMK1 信号通路导致肌动蛋白结合蛋白 cofilin (CFL1) 磷酸化 (PubMed:23633677)。该通路的激活导致 ACKR2 从核内体区室上调至细胞膜，提高其在趋化因子摄取和降解方面的效率 (PubMed:23633677)。通过清除组织、淋巴管表面和胎盘中的趋化因子，在炎症反应的消退（终止）和适应性免疫反应的调节中发挥重要作用 (PubMed:23479571)。在炎症消退过程中，对巨噬细胞的免疫沉默起主要作用 (By similarity)。作为炎性白细胞与淋巴管内皮细胞 (LECs) 相互作用的调节因子，并且是 LECs 区分未成熟/成熟树突状细胞所必需的 (PubMed:23479571)。 {ECO:0000250|UniProtKB:O08707, ECO:0000269|PubMed:18201974, ECO:0000269|PubMed:23479571, ECO:0000269|PubMed:23633677, ECO:0000303|PubMed:20373092}。

组织特异性

Found in endothelial cells lining afferent lymphatics in dermis and lymph nodes. Also found in lymph nodes subcapsular and medullary sinuses, tonsillar lymphatic sinuses and lymphatics in mucosa and submucosa of small and large intestine and appendix. Also found in some malignant vascular tumors. Expressed at high levels in Kaposi sarcoma-related pathologies. Expressed on apoptotic neutrophils (at protein level). Expressed primarily in placenta and fetal liver, and found at very low levels in the lung and lymph node.

亚细胞定位

Early endosome