S100A8 P05109

蛋白S100-A8 (Calgranulin-A) (钙卫蛋白 L1L 亚基) (囊性纤维化抗原) (CFAG) (白细胞 L1 复合物轻链) (迁移抑制因子相关蛋白 8) (MRP-8) (p8) (S100 钙结合蛋白 A8) (尿路结石蛋白条带 A)

功能描述

S100A8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。它能诱导中性粒细胞趋化和粘附。主要以钙卫蛋白（S100A8/A9）的形式存在，具有广泛的细胞内和细胞外功能。细胞内功能包括：促进白细胞花生四烯酸转运和代谢，调节吞噬细胞迁移过程中微管依赖性细胞骨架，以及激活中性粒细胞NADPH-氧化酶。还与CD69一起参与调节性T细胞分化（PubMed:26296369）。通过促进细胞膜上的酶复合物组装，将必需辅因子花生四烯酸转移到酶复合物，以及S100A8通过直接结合NCF2/P67PHOX促进酶组装，从而激活NADPH-氧化酶。细胞外功能涉及促炎、抗菌、清除氧化剂和诱导凋亡活性。其促炎活性包括募集白细胞，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。作为警报素或损伤相关分子模式（DAMP）分子，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。与TLR4和AGER结合激活MAP-kinase和NF-kappa-B信号通路，导致促炎级联反应的放大。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。可以通过自噬和凋亡诱导细胞死亡，该过程通过活性氧（ROS）介导的线粒体和溶酶体相互作用发生，并涉及BNIP3。可以通过抗凋亡作用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。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。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。iNOS-S100A8/A9转亚硝基化复合物通过识别[IL]-x-C-x-x-[DE]基序，指导GAPDH的选择性炎症刺激依赖性S-亚硝基化，可能还包括ANXA5、EZR、MSN和VIM等多个靶点；S100A8似乎有助于S-亚硝基化位点的选择性。{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:19935772, ECO:0000269|PubMed:21487906, ECO:0000269|PubMed:22363402, ECO:0000269|PubMed:22808130, ECO:0000269|PubMed:25417112, ECO:0000269|PubMed:26296369}.; FUNCTION: (Microbial infection) 在感染人冠状病毒SARS-CoV-2后，可能以依赖TLR4的方式诱导异常未成熟中性粒细胞的扩增。{ECO:0000305|PubMed:33388094}.

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. Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein. Note=Predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level, translocated from the cytoplasm to the cytoskeleton and the cell membrane. Upon neutrophil activation or endothelial adhesion of monocytes, is secreted via a microtubule-mediated, alternative pathway.