CD22

CD22
識別號
别名	CD22；, SIGLEC-2, SIGLEC2, CD22 molecule
外部ID	OMIM：107266 MGI：88322 HomoloGene：31052 GeneCards：CD22
基因位置（小鼠）
染色体	小鼠7号染色体
终止	30,579,767 bp
RNA表达模式
	; ; ; ;
	查阅更多表达数据
基因本體
分子功能	• 血浆蛋白结合; • carbohydrate binding; • IgM binding; • signaling receptor binding; • protein phosphatase binding; • sialic acid binding; • CD4 receptor binding;
細胞組分	• integral component of membrane; • 细胞膜; • 外排體; • 膜; • 細胞質; • 早期内吞体; • cell surface; • neuronal cell body membrane; • recycling endosome;
生物學過程	• 細胞粘附; • regulation of endocytosis; • regulation of B cell proliferation; • B cell activation; • regulation of immune response; • negative regulation of calcium-mediated signaling; • negative regulation of B cell receptor signaling pathway;
	Sources:Amigo / QuickGO
直系同源
	933
	12483
	无数据
	ENSMUSG00000030577
	P20273
	P35329
NM_024916; NM_001185099; NM_001185100; NM_001185101; NM_001278417;
	NM_001771
	NM_001043317; NM_009845
	NP_001172028; NP_001172029; NP_001172030; NP_001265346; NP_001762
	NP_001036782; NP_033975
	維基數據
檢視/編輯人類	檢視/編輯小鼠

CD22，名为分化簇-22（英語：cluster of differentiation-22），是成熟B细胞表面的一種跨膜受体，属于SIGLEC家族。^[4]

功能

CD22表現於成熟B细胞的表面，也表現於少量未成熟B细胞的表面，其主要功能是避免免疫系统过度激活，可降低罹患自體免疫性疾病的风险。^[5]

CD22是一种可高度特异性识别糖基化蛋白（如CD45）的跨膜蛋白，可通过N端的一个免疫球蛋白（Ig）结构域（英语：immunoglobulin domain）與唾液酸結合。因擁有Ig结构域，CD22也属于免疫球蛋白超家族（英语：immunoglobulin superfamily）。人类体内，CD22主要功能为抑制B細胞表面受體的活化。另外，小鼠實驗的結果發現B细胞運輸至派亞氏淋巴叢的過程亦有CD22的參與。^[6]

機制

CD22是B细胞受体的一個輔助受體（英语：co-receptor），其與連結在抗原B细胞受体表面的抗原連接後，自己會被磷酸化，進而活化一些磷酸酶以抑制免疫反應^[7]。

蛋白質交互作用

CD22经过实验证明会与以下蛋白質产生交互作用：Grb2（英语：Grb2）^[8]^[9]、PTPN6（英语：PTPN6）^[9]^[10]^[11]^[12]^[13]、LYN（英语：LYN）^[8]^[11]、SHC1（英语：SHC1）^[8]和INPP5D（英语：INPP5D）^[8]。

應用

CD22也可能作為抗癌藥物的標的，美国國立衛生研究院正在测试一种名为BL22（英语：Anti-CD22_immunotoxin）的免疫毒素（英语：immunotoxin），BL22是一種抗CD22的單株抗體，與CD22結合後可以進入細胞中，達到殺死細胞的效果，可能有助於治療某些種類的白血病^[14]。另外一種針對CD22的單株抗體藥物Epratuzumab（英语：Epratuzumab）也正在測試中，可能有助於治療白血病與全身性紅斑狼瘡^[15]。

参考文献

^ ^1.0 ^1.1 ^1.2 GRCm38: Ensembl release 89: ENSMUSG00000030577 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Crocker PR, et al. Siglecs: a family of sialic-acid binding lectins. Glycobiology. February 1998, 8 (2): v. PMID 9498912. doi:10.1093/glycob/8.2.0.
^ Hatta; et al. Identification of the gene variations in human CD22. Immunogenetics. 1999, 49 (4): 280–286 [2018-08-15]. doi:10.1007/s002510050494. （原始内容存档于2019-09-24）.
^ Lee M, Kiefel H, LaJevic MD, Macauley MS, Kawashima H, O'Hara E, Pan J, Paulson JC, Butcher EC. Transcriptional programs of lymphoid tissue capillary and high endothelium reveal control mechanisms for lymphocyte homing. Nature Immunology. October 2014, 15 (10): 982–95. PMC 4222088 . PMID 25173345. doi:10.1038/ni.2983.
^ Dörner T, Shock A, Smith KG. CD22 and Autoimmune Disease 31 (5). International Reviews of Immunology. 2012. doi:10.3109/08830185.2012.709890.
^ ^8.0 ^8.1 ^8.2 ^8.3 Poe JC, Fujimoto M, Jansen PJ, Miller AS, Tedder TF. CD22 forms a quaternary complex with SHIP, Grb2, and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux. The Journal of Biological Chemistry. June 2000, 275 (23): 17420–7. PMID 10748054. doi:10.1074/jbc.M001892200.
^ ^9.0 ^9.1 Otipoby KL, Draves KE, Clark EA. CD22 regulates B cell receptor-mediated signals via two domains that independently recruit Grb2 and SHP-1. The Journal of Biological Chemistry. November 2001, 276 (47): 44315–22. PMID 11551923. doi:10.1074/jbc.M105446200.
^ Blasioli J, Paust S, Thomas ML. Definition of the sites of interaction between the protein tyrosine phosphatase SHP-1 and CD22. The Journal of Biological Chemistry. January 1999, 274 (4): 2303–7. PMID 9890995. doi:10.1074/jbc.274.4.2303.
^ ^11.0 ^11.1 Greer SF, Justement LB. CD45 regulates tyrosine phosphorylation of CD22 and its association with the protein tyrosine phosphatase SHP-1. Journal of Immunology. May 1999, 162 (9): 5278–86. PMID 10228003.
^ Law CL, Sidorenko SP, Chandran KA, Zhao Z, Shen SH, Fischer EH, Clark EA. CD22 associates with protein tyrosine phosphatase 1C, Syk, and phospholipase C-gamma(1) upon B cell activation. The Journal of Experimental Medicine. February 1996, 183 (2): 547–60. PMC 2192439 . PMID 8627166. doi:10.1084/jem.183.2.547.
^ Adachi T, Wienands J, Wakabayashi C, Yakura H, Reth M, Tsubata T. SHP-1 requires inhibitory co-receptors to down-modulate B cell antigen receptor-mediated phosphorylation of cellular substrates. The Journal of Biological Chemistry. July 2001, 276 (28): 26648–55. PMID 11356834. doi:10.1074/jbc.M100997200.
^ BL22 Immunotoxin in Treating Patients Previously Treated With Cladribine for Hairy Cell Leukemia. ClinicalTrials.gov - U.S. National Institutes of Health. [2018-08-14]. （原始内容存档于2007-10-07）.
^ Epratuzumab. DrugBank. Canadian Institutes of Health Research. [2018-08-16]. （原始内容存档于2016-03-04）.

外部链接

醫學主題詞表（MeSH）：CD22+Antigen

[refGRCm38Ensembl-1] 1.0 ^1.1 ^1.2 GRCm38: Ensembl release 89: ENSMUSG00000030577 - Ensembl, May 2017

[2] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9498912-4] Crocker PR, et al. Siglecs: a family of sialic-acid binding lectins. Glycobiology. February 1998, 8 (2): v. PMID 9498912. doi:10.1093/glycob/8.2.0.

[Hatta1999-5] Hatta; et al. Identification of the gene variations in human CD22. Immunogenetics. 1999, 49 (4): 280–286 [2018-08-15]. doi:10.1007/s002510050494. （原始内容存档于2019-09-24）.

[6] Lee M, Kiefel H, LaJevic MD, Macauley MS, Kawashima H, O'Hara E, Pan J, Paulson JC, Butcher EC. Transcriptional programs of lymphoid tissue capillary and high endothelium reveal control mechanisms for lymphocyte homing. Nature Immunology. October 2014, 15 (10): 982–95. PMC 4222088 . PMID 25173345. doi:10.1038/ni.2983.

[7] Dörner T, Shock A, Smith KG. CD22 and Autoimmune Disease 31 (5). International Reviews of Immunology. 2012. doi:10.3109/08830185.2012.709890.

[pmid10748054-8] 8.0 ^8.1 ^8.2 ^8.3 Poe JC, Fujimoto M, Jansen PJ, Miller AS, Tedder TF. CD22 forms a quaternary complex with SHIP, Grb2, and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux. The Journal of Biological Chemistry. June 2000, 275 (23): 17420–7. PMID 10748054. doi:10.1074/jbc.M001892200.

[pmid11551923-9] 9.0 ^9.1 Otipoby KL, Draves KE, Clark EA. CD22 regulates B cell receptor-mediated signals via two domains that independently recruit Grb2 and SHP-1. The Journal of Biological Chemistry. November 2001, 276 (47): 44315–22. PMID 11551923. doi:10.1074/jbc.M105446200.

[pmid9890995-10] Blasioli J, Paust S, Thomas ML. Definition of the sites of interaction between the protein tyrosine phosphatase SHP-1 and CD22. The Journal of Biological Chemistry. January 1999, 274 (4): 2303–7. PMID 9890995. doi:10.1074/jbc.274.4.2303.

[pmid10228003-11] 11.0 ^11.1 Greer SF, Justement LB. CD45 regulates tyrosine phosphorylation of CD22 and its association with the protein tyrosine phosphatase SHP-1. Journal of Immunology. May 1999, 162 (9): 5278–86. PMID 10228003.

[pmid8627166-12] Law CL, Sidorenko SP, Chandran KA, Zhao Z, Shen SH, Fischer EH, Clark EA. CD22 associates with protein tyrosine phosphatase 1C, Syk, and phospholipase C-gamma(1) upon B cell activation. The Journal of Experimental Medicine. February 1996, 183 (2): 547–60. PMC 2192439 . PMID 8627166. doi:10.1084/jem.183.2.547.

[pmid11356834-13] Adachi T, Wienands J, Wakabayashi C, Yakura H, Reth M, Tsubata T. SHP-1 requires inhibitory co-receptors to down-modulate B cell antigen receptor-mediated phosphorylation of cellular substrates. The Journal of Biological Chemistry. July 2001, 276 (28): 26648–55. PMID 11356834. doi:10.1074/jbc.M100997200.

[titleBL22_Immunotoxin_in_Treating_Patients_Previously_Treated_With_Cladribine_for_Hairy_Cell_Leukemia_-_Full_Text_View_-_ClinicalTrials.gov-14] BL22 Immunotoxin in Treating Patients Previously Treated With Cladribine for Hairy Cell Leukemia. ClinicalTrials.gov - U.S. National Institutes of Health. [2018-08-14]. （原始内容存档于2007-10-07）.

[15] Epratuzumab. DrugBank. Canadian Institutes of Health Research. [2018-08-16]. （原始内容存档于2016-03-04）.

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