NLRP3 Q96P20

含NACHT、LRR和PYD结构域蛋白3 (EC 3.6.4.-) (血管紧张素/加压素受体AII/AVP样) (Caterpiller蛋白1.1) (CLR1.1) (冷诱导自身炎症综合征1蛋白) (Cryopyrin) (含PYRIN的APAF1样蛋白1)

功能描述

NLRP3炎症小体的传感器组分，介导炎症小体响应膜完整性缺陷时的激活，导致炎症细胞因子IL1B和IL18的分泌以及细胞焦亡 (PubMed:16407889, PubMed:18403674, PubMed:18604214, PubMed:23582325, PubMed:25686105, PubMed:27929086, PubMed:28656979, PubMed:28847925, PubMed:30487600, PubMed:30612879, PubMed:31086327, PubMed:31086329, PubMed:31189953, PubMed:33231615, PubMed:34133077, PubMed:34341353, PubMed:34512673, PubMed:36442502, PubMed:40450990)。响应影响膜完整性的病原体和其他损伤相关信号，启动由NLRP3、CASP1和PYCARD/ASC组成的炎症小体聚合复合物的形成 (PubMed:16407889, PubMed:18403674, PubMed:27432880, PubMed:28847925, PubMed:31189953, PubMed:33231615, PubMed:34133077, PubMed:34341353, PubMed:36142182, PubMed:36442502)。前体caspase-1 (proCASP1) 募集到NLRP3炎症小体促进caspase-1 (CASP1) 激活，随后切割并激活炎症细胞因子IL1B和IL18以及gasdermin-D (GSDMD)，促进细胞因子分泌和细胞焦亡 (PubMed:23582325, PubMed:28847925, PubMed:31189953, PubMed:33231615, PubMed:34133077, PubMed:34341353)。NLRP3炎症小体的激活也是HMGB1分泌所必需的；刺激炎症反应 (PubMed:22801494)。参与组织损伤后的稳态伤口愈合反应，这是一个指导中性粒细胞迁移到坏死部位同时避免健康组织附带损伤的多步骤级联反应。坏死细胞释放的ATP通过P2RX7信号传导触发NLRP3炎症小体激活，导致中性粒细胞粘附于损伤部位附近的血管内皮 (By similarity)。在静息条件下，结合ADP的NLRP3处于自抑制状态 (PubMed:35114687)。NLRP3激活刺激包括细胞外ATP、尼日利亚菌素、活性氧、单尿酸钠或胆固醇晶体、淀粉样蛋白β纤维、环境或工业颗粒及纳米颗粒（如石棉、二氧化硅、铝盐）、胞质dsRNA等 (PubMed:16407889, PubMed:18403674, PubMed:18604214, PubMed:19414800, PubMed:23871209)。几乎所有刺激都触发细胞内K(+)外流 (By similarity)。这些刺激导致膜扰动和NLRP3激活 (By similarity)。激活后，NLRP3被转运至微管组织中心 (MTOC)，在那里被NEK7解锁，导致其重定位至分散的高尔基体网络 (dTGN) 囊泡膜并形成活性炎症小体复合物 (PubMed:36442502, PubMed:39173637)。通过结合磷酸肌醇-4-磷酸 (PtdIns4P) 与dTGN囊泡膜结合 (PubMed:30487600, PubMed:34554188)。显示ATP酶活性 (PubMed:17483456)。 {ECO:0000250|UniProtKB:Q8R4B8, ECO:0000269|PubMed:16407889, ECO:0000269|PubMed:17483456, ECO:0000269|PubMed:18403674, ECO:0000269|PubMed:18604214, ECO:0000269|PubMed:19414800, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:23582325, ECO:0000269|PubMed:23871209, ECO:0000269|PubMed:25686105, ECO:0000269|PubMed:27432880, ECO:0000269|PubMed:27929086, ECO:0000269|PubMed:28656979, ECO:0000269|PubMed:28847925, ECO:0000269|PubMed:30487600, ECO:0000269|PubMed:30612879, ECO:0000269|PubMed:31086327, ECO:0000269|PubMed:31086329, ECO:0000269|PubMed:31189953, ECO:0000269|PubMed:33231615, ECO:0000269|PubMed:34133077, ECO:0000269|PubMed:34341353, ECO:0000269|PubMed:34554188, ECO:0000269|PubMed:35114687, ECO:0000269|PubMed:36142182, ECO:0000269|PubMed:36442502, ECO:0000269|PubMed:39173637, ECO:0000269|PubMed:40450990}.; FUNCTION: 独立于炎症小体激活，调节T辅助细胞2 (Th2) 的分化，并在Th2细胞依赖性哮喘和肿瘤生长中发挥作用 (By similarity)。在Th2分化过程中，是IRF4最佳结合IL4启动子以及IRF4依赖性IL4转录所必需的 (By similarity)。结合共有DNA序列 5'-GRRGGNRGAG-3' (By similarity)。可能也参与IL5、IL13、GATA3、CCR3、CCR4和MAF的转录 (By similarity)。 {ECO:0000250|UniProtKB:Q8R4B8}.

组织特异性

Predominantly expressed in macrophages (PubMed:33231615, PubMed:34133077). Also expressed in dendritic cells, B- and T-cells (at protein level) (PubMed:11786556, PubMed:17164409). Expressed in LPS-treated granulocytes, but not in resting cells (at protein level) (PubMed:17164409). Expression in monocytes is very weak (at protein level) (PubMed:17164409). Expressed in stratified non-keratinizing squamous epithelium, including oral, esophageal and ectocervical mucosa and in the Hassall's corpuscles in the thymus. Also, detected in the stratified epithelium covering the bladder and ureter (transitional mucosa) (at protein level) (PubMed:17164409). Expressed in lung epithelial cells (at protein level) (PubMed:23229815). Expressed in chondrocytes (PubMed:12032915). Expressed at low levels in resting osteoblasts (PubMed:17907925).

亚细胞定位

Cytoplasm, cytosol