NLRP1 Q9C000

含NACHT、LRR和PYD结构域蛋白1 (EC 3.4.-.-) (EC 3.6.4.-) (含半胱天冬酶招募结构域蛋白7) (死亡效应因子细丝形成ced-4样凋亡蛋白) (核苷酸结合结构域和半胱天冬酶招募结构域) [裂解为：含NACHT、LRR和PYD结构域蛋白1，C端 (NLRP1-CT)；含NACHT、LRR和PYD结构域蛋白1，N端 (NLRP1-NT)]

功能描述

作为NLRP1炎症小体的传感器组分，响应各种病原体相关信号介导炎症小体激活，导致随后的细胞焦亡 (PubMed:12191486, PubMed:17349957, PubMed:22665479, PubMed:27662089, PubMed:31484767, PubMed:33093214, PubMed:33410748, PubMed:33731929, PubMed:33731932, PubMed:35857590)。炎症小体是在细胞质中响应病原体和其他损伤相关信号组装的超分子复合物，在先天免疫和炎症中发挥关键作用 (PubMed:12191486, PubMed:17349957, PubMed:22665479)。作为识别受体 (PRR)：识别特定病原体和其他损伤相关信号，例如被某些人类肠道病毒和鼻病毒切割、双链RNA、UV-B照射或Val-boroPro抑制剂，并介导由NLRP1、CASP1和PYCARD/ASC组成的炎症小体聚合复合物的形成 (PubMed:12191486, PubMed:17349957, PubMed:22665479, PubMed:25562666, PubMed:30096351, PubMed:30291141, PubMed:33093214, PubMed:33243852, PubMed:33410748, PubMed:35857590)。响应病原体相关信号，NLRP1的N端部分被蛋白酶体降解，释放蛋白切割后的C端部分 (NACHT, LRR and PYD domains-containing protein 1, C-terminus)，该部分聚合并与PYCARD/ASC结合启动炎症小体复合物的形成：NLRP1炎症小体招募pro-caspase-1 (proCASP1) 并促进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)，导致细胞焦亡 (PubMed:12191486, PubMed:17349957, PubMed:22665479, PubMed:32051255, PubMed:33093214)。在缺乏GSDMD表达的情况下，NLRP1炎症小体能够招募并激活CASP8，导致gasdermin-E (GSDME) 的激活 (PubMed:33852854, PubMed:35594856)。NLRP1炎症小体的激活也是HMGB1分泌所必需的；活化的细胞因子和HMGB1刺激炎症反应 (PubMed:22801494)。结合ATP并显示ATP酶活性 (PubMed:11113115, PubMed:15212762, PubMed:33243852)。在人类气道上皮细胞的抗病毒免疫和炎症中发挥重要作用 (PubMed:33093214)。特异性识别多种病原体相关信号：在感染人鼻病毒14和16 (HRV-14和HRV-16) 后，NLRP1被切割并激活，触发依赖NLRP1的炎症小体激活和IL18分泌 (PubMed:33093214)。正链RNA病毒，如塞姆利基森林病毒和长链dsRNA激活NLRP1炎症小体，以依赖NLRP1的方式触发IL1B释放 (PubMed:33243852)。作为长链dsRNA并因此作为RNA病毒感染的直接传感器 (PubMed:33243852)。也可能被细菌肽聚糖片段胞壁酰二肽 (MDP) 以依赖NOD2的方式激活 (PubMed:18511561)。NLRP1炎症小体也响应导致核糖体碰撞的UV-B照射而被激活：核糖体碰撞以依赖MAP3K20的方式引起NLRP1的磷酸化和激活，导致细胞焦亡 (PubMed:35857590)。 {ECO:0000269|PubMed:11113115, ECO:0000269|PubMed:12191486, ECO:0000269|PubMed:15212762, ECO:0000269|PubMed:17349957, ECO:0000269|PubMed:18511561, ECO:0000269|PubMed:22665479, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:25562666, ECO:0000269|PubMed:27662089, ECO:0000269|PubMed:30096351, ECO:0000269|PubMed:30291141, ECO:0000269|PubMed:31484767, ECO:0000269|PubMed:32051255, ECO:0000269|PubMed:33093214, ECO:0000269|PubMed:33243852, ECO:0000269|PubMed:33410748, ECO:0000269|PubMed:33731929, ECO:0000269|PubMed:33731932, ECO:0000269|PubMed:33852854, ECO:0000269|PubMed:35594856, ECO:0000269|PubMed:35857590}.; FUNCTION: [NACHT, LRR and PYD domains-containing protein 1]: 构成NLRP1炎症小体的前体，其在FIIND结构域内介导自蛋白水解加工，生成N端和C端部分，在缺乏病原体和其他损伤相关信号时，这两部分非共价结合。 {ECO:0000269|PubMed:22087307}.; FUNCTION: [NACHT, LRR and PYD domains-containing protein 1, N-terminus]: 阻止NLRP1炎症小体形成的调节部分：在缺乏病原体和其他损伤相关信号时，与NLRP1的C端部分 (NACHT, LRR and PYD domains-containing protein 1, C-terminus) 相互作用，阻止NLRP1炎症小体的激活 (PubMed:33093214)。响应病原体相关信号，该部分被泛素化并被蛋白酶体降解，释放蛋白切割后的C端部分，该部分聚合并形成NLRP1炎症小体 (PubMed:33093214)。 {ECO:0000269|PubMed:33093214}.; FUNCTION: [NACHT, LRR and PYD domains-containing protein 1, C-terminus]: 构成NLRP1炎症小体的活性部分 (PubMed:33093214, PubMed:33731929, PubMed:33731932)。在缺乏病原体和其他损伤相关信号时，与NLRP1的N端部分 (NACHT, LRR and PYD domains-containing protein 1, N-terminus) 相互作用，阻止NLRP1炎症小体的激活 (PubMed:33093214)。响应病原体相关信号，NLRP1的N端部分被蛋白酶体降解，释放该形式，其聚合并与PYCARD/ASC结合形成NLRP1炎症小体复合物：NLRP1炎症小体复合物随后直接招募pro-caspase-1 (proCASP1) 并促进caspase-1 (CASP1) 激活，导致gasdermin-D (GSDMD) 切割及随后的细胞焦亡 (PubMed:33093214)。 {ECO:0000269|PubMed:33093214, ECO:0000269|PubMed:33731929, ECO:0000269|PubMed:33731932}.; FUNCTION: [Isoform 2]: 尚不清楚是否参与炎症小体形成。它不在FIIND结构域内被切割，不组装成斑点，也不促进IL1B释放 (PubMed:22665479)。然而，在体外无细胞系统中，已显示其可被MDP激活 (PubMed:17349957)。 {ECO:0000269|PubMed:17349957, ECO:0000269|PubMed:22665479}.

组织特异性

Widely expressed (PubMed:11113115, PubMed:17164409). Abundantly expressed in primary immune cells (isoform 1 and isoform 2), including in neutrophils, monocytes/macrophages, dendritic cells (mostly Langerhans cells), and B- and T-lymphocytes (at protein level) (PubMed:15285719, PubMed:17164409). Strongly expressed in epithelial cells lining the glandular epithelium, such as that of the gastrointestinal tract (stomach, small intestine, colon), the respiratory tract (trachea and bronchi), and the endometrial and endocervical glands, gallbladder, prostate, and breast (at protein level). In testis, expressed in spermatogonia and primary spermatocytes, but not in Sertoli cells (at protein level). In the brain, expressed in neurons, in particular in pyramidal ones and in oligodendrocytes, but not detected in microglia (at protein level) (PubMed:17164409). Expressed in adult and fetal ocular tissues, including in adult and 24-week old fetal choroid, sclera, cornea, and optic nerve, as well as in adult retina and fetal retina/retinal pigment epithelium (PubMed:23349227). Highly expressed in the skin throughout the epidermis and in dermal fibroblasts, in both glabrous skin and plantar skin. It is detected in keratinocytes, but not in melanocytes. Expressed in epidermal appendages such as hair follicles (PubMed:27662089).

亚细胞定位

Cytoplasm, cytosol