TLR9

Toll样受体9（英语：Toll-like receptor 9）是由人类基因 TLR9 编码的蛋白质^[1]，也被称为CD289（分化簇289，cluster of differentiation 289），是Toll样受体（TLR）家族的成员。

Toll-like receptor 9
标识
代号	TLR9; CD289
扩展标识	遗传学：605474 鼠基因：1932389 同源基因：68126 ChEMBL: 5804 GeneCards: TLR9 Gene
基因本体论描述 分子功能 · transmembrane signaling receptor activity · interleukin-1 receptor binding · siRNA binding 细胞成分 · Golgi membrane · extracellular region · cytoplasm · lysosome · endosome · endoplasmic reticulum · endoplasmic reticulum membrane · plasma membrane · endosome membrane · integral component of membrane · basolateral plasma membrane · apical plasma membrane · early phagosome · endolysosome membrane 生物过程 · toll-like receptor signaling pathway · response to molecule of bacterial origin · MyD88-dependent toll-like receptor signaling pathway · inflammatory response · I-kappaB phosphorylation · insulin receptor signaling pathway · positive regulation of gene expression · maintenance of gastrointestinal epithelium · negative regulation of NF-kappaB transcription factor activity · tumor necrosis factor production · negative regulation of interleukin-6 production · negative regulation of interleukin-8 production · positive regulation of chemokine production · positive regulation of granulocyte macrophage colony-stimulating factor production · positive regulation of interferon-beta production · positive regulation of interleukin-10 production · positive regulation of interleukin-12 production · positive regulation of interleukin-18 production · positive regulation of interleukin-6 production · positive regulation of interleukin-8 production · positive regulation of tumor necrosis factor production · negative regulation of toll-like receptor signaling pathway · positive regulation of toll-like receptor signaling pathway · toll-like receptor 9 signaling pathway · positive regulation of NF-kappaB import into nucleus · defense response to bacterium · positive regulation of I-kappaB kinase/NF-kappaB signaling · positive regulation of JUN kinase activity · positive regulation of interferon-gamma biosynthetic process · innate immune response · positive regulation of interferon-alpha biosynthetic process · positive regulation of interferon-beta biosynthetic process · positive regulation of transcription from RNA polymerase II promoter · positive regulation of JNK cascade · regulation of cytokine secretion · positive regulation of inflammatory response · defense response to Gram-negative bacterium · positive regulation of NF-kappaB transcription factor activity · positive regulation of nitric-oxide synthase biosynthetic process · negative regulation of calcium-transporting ATPase activity Sources: Amigo / QuickGO
直系同源体
物种	人类	小鼠
Entrez	54106	81897
Ensembl	ENSG00000239732	ENSMUSG00000045322
UniProt	Q9NR96	Q9EQU3
mRNA序列	NM_017442	NM_031178
蛋白序列	NP_059138	NP_112455
基因位置	Chr 3: 52.22 – 52.23 Mb	Chr 9: 106.22 – 106.23 Mb
PubMed查询	[1]	[2]
查 论 编

功能

TLR家族的受体在病原识别与先天免疫的激活中起着基础作用。TLRs are named for the high degree of conservation in structure and function seen between mammalian TLRs and the Drosophila transmembrane protein Toll. TLRs是呈现在细胞表面和胞内间室的跨膜蛋白，用以识别病原体呈现的病原相关分子模式（Pathogen-associated molecular patterns，PAMPs），然后启动制造先天和获得性免疫所需的细胞因子的信号。 The various TLRs exhibit different patterns of expression. 这一基因通常表达于富含免疫细胞的组织，比如脾、淋巴结、骨髓等。研究指出，在小鼠和人中的TLR9受体可响应细菌DNA中的未甲基化的CpG寡脱氧核苷酸序列来激活先天免疫应答^[2]。

TLR9可以识别DNA分子中的未甲基化的CpG序列，CpG位点在脊椎动物非常稀少（~1%），但在细菌或病毒基因组中很丰富。TLR9在免疫系统的多种细胞中有表达，如B淋巴细胞、单核细胞、自然杀伤细胞（NK）和浆细胞样树突状细胞。TLR9表达于细胞内，是核内体的组分之一，其功能为当细菌或病毒感染时结合其DNA上的富CpG基序来改变免疫系统的状态。TLR9的信号会导致细胞启动炎症反应，并分泌相关细胞因子，如I型干扰素和IL-12等。

临床意义

There are new immunomodulatory treatments undergoing testing which involve the administration of artificial DNA oligonucleotides containing the CpG motif. CpG DNA has applications in treating allergies such as asthma,^[3] immunostimulation against cancer,^[4] immunostimulation against pathogens, and as adjuvants in vaccines.^[5]

蛋白质相互作用

• TLR9 可以与RNF216交互作用发生^[6]。
• 它可以被CpG寡脱氧核苷酸激活，如阿托莫德（英语：Agatolimod）。

参考文献

1. Du X, Poltorak A, Wei Y, Beutler B. Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur Cytokine Netw. Dec 2000, 11 (3): 362–71. PMID 11022119.
2. Entrez Gene: TLR9 toll-like receptor 9.
3. Kline JN. Eat dirt: CpG DNA and immunomodulation of asthma. Proc Am Thorac Soc. July 2007, 4 (3): 283–8. PMC 2647631 . PMID 17607014. doi:10.1513/pats.200701-019AW.
4. Thompson JA, Kuzel T, Bukowski R, Masciari F, Schmalbach T. Phase Ib trial of a targeted TLR9 CpG immunomodulator (CPG 7909) in advanced renal cell carcinoma (RCC). Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). July 2004, 22 (14S) [2016-01-14]. （原始内容存档于2012-03-08）.
5. Klinman DM. Adjuvant activity of CpG oligodeoxynucleotides. Int. Rev. Immunol. 2006, 25 (3-4): 135–54. PMID 16818369. doi:10.1080/08830180600743057.
6. Chuang TH, Ulevitch RJ. Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors. Nat. Immunol. May 2004, 5 (5): 495–502. PMID 15107846. doi:10.1038/ni1066.

延伸阅读

• Lien E, Ingalls RR. Toll-like receptors.. Crit. Care Med. 2002, 30 (1 Suppl): S1–11. PMID 11782555. doi:10.1097/00003246-200201001-00001.
• Kaisho T, Akira S. Toll-like receptors as adjuvant receptors.. Biochim. Biophys. Acta. 2002, 1589 (1): 1–13. PMID 11909637. doi:10.1016/S0167-4889(01)00182-3.

外部链接

• 医学主题词表（MeSH）：TLR9+protein,+human

TLR9引用了美国国家医学图书馆提供的资料，这些资料属于公共领域。