S100A9 P06702

蛋白质 S100-A9 (钙粒蛋白-B) (钙卫蛋白 L1H 亚基) (白细胞 L1 复合物重链) (迁移抑制因子相关蛋白 14) (MRP-14) (p14) (S100 钙结合蛋白 A9)

功能描述

S100A9是一种钙和锌结合蛋白，在炎症过程和免疫反应的调节中发挥重要作用 (PubMed:12626582, PubMed:15331440, PubMed:16258195, PubMed:19122197, PubMed:20103766, PubMed:21325622, PubMed:8423249)。它能诱导中性粒细胞趋化、粘附，能通过激活SYK、PI3K/AKT和ERK1/2促进吞噬作用从而增加中性粒细胞的杀菌活性，并能通过MAPK依赖机制诱导中性粒细胞脱颗粒 (PubMed:12626582, PubMed:15331440, PubMed:20103766)。主要以钙卫蛋白（calprotectin，S100A8/A9）的形式存在，具有广泛的细胞内和细胞外功能 (PubMed:16258195, PubMed:19122197, PubMed:8423249)。细胞内功能包括：促进白细胞花生四烯酸的转运和代谢，调节吞噬细胞迁移过程中微管蛋白依赖性细胞骨架，以及激活中性粒细胞NADPH-氧化酶 (PubMed:15331440, PubMed:21325622)。还与CD69一起参与调节性T细胞的分化 (PubMed:26296369)。通过促进细胞膜上的酶复合物组装来激活NADPH-氧化酶，将必需辅助因子花生四烯酸转移给酶复合物，S100A8则通过直接结合NCF2/P67PHOX参与酶的组装 (PubMed:15642721, PubMed:22808130)。细胞外功能涉及促炎、抗菌、清除氧化剂和诱导细胞凋亡活性 (PubMed:19534726, PubMed:8423249)。其促炎活性包括白细胞募集，促进细胞因子和趋化因子的产生，以及调节白细胞粘附和迁移 (PubMed:15598812, PubMed:21487906)。作为警报素或损伤相关分子模式（DAMP）分子发挥作用，通过结合模式识别受体如Toll样受体4（TLR4）和晚期糖基化终产物受体（AGER）刺激先天免疫细胞 (PubMed:19402754)。与TLR4和AGER结合激活MAP-激酶和NF-kappa-B信号通路，导致促炎级联反应放大 (PubMed:19402754, PubMed:22804476)。对细菌和真菌具有抗菌活性，其抗菌活性可能通过螯合微生物生长必需的Zn(2+)来实现 (PubMed:19087201)。能通过自噬和凋亡诱导细胞死亡，这是通过活性氧（ROS）介导的线粒体和溶酶体相互作用发生的，该过程涉及BNIP3 (PubMed:19935772)。能通过抗凋亡效应调节中性粒细胞数量和凋亡；通过ITGAM/ITGB和TLR4以及涉及MEK-ERK的信号机制调节细胞存活 (PubMed:22363402)。其作为氧化剂清除剂的作用具有保护作用，通过清除氧化剂防止组织过度损伤 (PubMed:21912088, PubMed:22489132)。在自身免疫以及癌症发展和肿瘤扩散中可作为炎症的有效放大器 (PubMed:16258195)。具有转亚硝基化酶活性；在氧化修饰的低密度脂蛋白（LDL(ox)）诱导的GAPDH 'Cys-247' S-亚硝基化中，提议将其自身的S-亚硝基化Cys-3上的NO基团从NOS2/iNOS转移给GAPDH (PubMed:25417112)。提议iNOS-S100A8/A9转亚硝基化酶复合物通过识别[IL]-x-C-x-x-[DE]基序，指导多种靶点如ANXA5、EZR、MSN和VIM的选择性炎症刺激依赖性S-亚硝基化 (PubMed:25417112)。 {ECO:0000269|PubMed:12626582, ECO:0000269|PubMed:15331440, ECO:0000269|PubMed:15598812, ECO:0000269|PubMed:15642721, ECO:0000269|PubMed:16258195, ECO:0000269|PubMed:19087201, ECO:0000269|PubMed:19122197, ECO:0000269|PubMed:19402754, ECO:0000269|PubMed:19534726, ECO:0000269|PubMed:19935772, ECO:0000269|PubMed:20103766, ECO:0000269|PubMed:21325622, ECO:0000269|PubMed:21487906, ECO:0000269|PubMed:22363402, ECO:0000269|PubMed:22804476, ECO:0000269|PubMed:22808130, ECO:0000269|PubMed:25417112, ECO:0000269|PubMed:26296369, ECO:0000269|PubMed:8423249, ECO:0000303|PubMed:21912088, ECO:0000303|PubMed:22489132}.

组织特异性

Calprotectin (S100A8/9) is predominantly expressed in myeloid cells. Except for inflammatory conditions, the expression is restricted to a specific stage of myeloid differentiation since both proteins are expressed in circulating neutrophils and monocytes but are absent in normal tissue macrophages and lymphocytes. Under chronic inflammatory conditions, such as psoriasis and malignant disorders, also expressed in the epidermis. Found in high concentrations at local sites of inflammation or in the serum of patients with inflammatory diseases such as rheumatoid, cystic fibrosis, inflammatory bowel disease, Crohn's disease, giant cell arteritis, cystic fibrosis, Sjogren's syndrome, systemic lupus erythematosus, and progressive systemic sclerosis. Involved in the formation and deposition of amyloids in the aging prostate known as corpora amylacea inclusions. Strongly up-regulated in many tumors, including gastric, esophageal, colon, pancreatic, bladder, ovarian, thyroid, breast and skin cancers.

亚细胞定位

Secreted. Cytoplasm