CD22

CD22
识别号
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
基因本体
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;
细胞组分	• integral component of membrane; • 细胞膜; • 外排体; • 膜; • 细胞质; • 早期内吞体; • cell surface; • neuronal cell body membrane; • recycling endosome;
生物学过程	• 细胞粘附; • 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
	维基数据
查看/编辑人类	查看/编辑小鼠

CD22，名为分化簇-22（英语：cluster of differentiation-22），是成熟B细胞表面的一种跨膜受体，属于SIGLEC家族。^[4]

功能

CD22表现于成熟B细胞的表面，也表现于少量未成熟B细胞的表面，其主要功能是避免免疫系统过度激活，可降低罹患自体免疫性疾病的风险。^[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）与唾液酸结合。因拥有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细胞表面受体的活化。另外，小鼠实验的结果发现B细胞运输至派亚氏淋巴丛的过程亦有CD22的参与。^[6]

机制

CD22是B细胞受体的一个辅助受体（英语：co-receptor），其与连结在抗原B细胞受体表面的抗原连接后，自己会被磷酸化，进而活化一些磷酸酶以抑制免疫反应^[7]。

蛋白质交互作用

CD22经过实验证明会与以下蛋白质产生交互作用：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]。

应用

CD22也可能作为抗癌药物的标的，美国国立卫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是一种抗CD22的单株抗体，与CD22结合后可以进入细胞中，达到杀死细胞的效果，可能有助于治疗某些种类的白血病^[14]。另外一种针对CD22的单株抗体药物Epratuzumab（英语：Epratuzumab）也正在测试中，可能有助于治疗白血病与全身性红斑狼疮^[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

医学主题词表（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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