激活诱导性胞苷脱氨酶

激活诱导胞苷脱氨酶
已知的结构
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	5JJ4
识别号
别名	AICDA；, AID, ARP2, CDA2, HEL-S-284, HIGM2, activation-induced cytidine deaminase, activation induced cytidine deaminase
外部ID	OMIM：605257 MGI：1342279 HomoloGene：7623 GeneCards：AICDA
相关疾病
	第二型高免疫球蛋白M综合征
基因位置（人类）
染色体	12号染色体
终止	8,613,242 bp
基因位置（小鼠）
染色体	小鼠6号染色体
终止	122,541,139 bp
RNA表达模式
	查阅更多表达数据
基因本体
分子功能	• hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines; • 锌离子结合; • 血浆蛋白结合; • 催化活性; • 水解酶活性; • 泛素蛋白连接酶结合; • 金属离子结合; • cytidine deaminase activity; • 相同蛋白质结合; • RNA binding;
细胞组分	• 外切体复合物; • 细胞核; • 细胞质; • 处理小体; • 大分子复合体;
生物学过程	• somatic hypermutation of immunoglobulin genes; • DNA去甲基化; • mRNA processing; • B cell differentiation; • somatic diversification of immunoglobulins; • negative regulation of DNA methylation-dependent heterochromatin assembly; • cytidine deamination; • cellular response to lipopolysaccharide; • 免疫球蛋白类型转换; • defense response to bacterium; • regulation of DNA stability; • negative regulation of transposition; • cytidine to uridine editing; • regulation of nuclear cell cycle DNA replication; • negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; • defense response to virus; • DNA cytosine deamination;
	Sources:Amigo / QuickGO
直系同源
	57379
	11628
	ENSG00000111732
	ENSMUSG00000040627
	Q9GZX7
	Q9WVE0
	NM_020661; NM_001330343
	NM_009645
	NP_001317272; NP_065712
	NP_033775
	维基数据
查看/编辑人类	查看/编辑小鼠

激活诱导性胞苷脱氨酶（Activation-induced cytidine deaminase，简称AID）是一种胞苷脱氨酶（英语：Cytidine deaminase），属APOBEC（英语：APOBEC）脱氨酶家族，在人类基因组中由12号染色体上的AICDA基因编码，大小约为24kDa^[6]，可催化胞苷（C）脱氨转为尿苷（U）的反应，即将DNA上的C:G配对转为U:G误配，且因DNA复制时会将U视为T，最终会导致U:G转为T:A的转换突变^[7]^[8]。U:G误配也可能被细胞中的碱基切除修复（BER）或错误配对修复（MMR）机制修补，BER途径中此误配可被尿嘧啶DNA糖基酶（英语：Uracil-DNA glycosylase）（UDG）识别而切除，形成AP位点，接着可能由DNA聚合酶η（英语：DNA polymerase eta）等易误（error-prone）的聚合酶随机补上碱基而完成修补（短补丁修复），或将下游数个碱基由内切酶切除后再合成新的核苷酸以完成修补（长补丁修复）^[9]；MMR途径中，U:G误配则会被MutSα复合体识别而被切除，再由易误的聚合酶随机补上碱基，两种修复机制皆可能造成突变^[10]。DNA转录时暂时呈单股的状态有利于激活诱导性胞苷脱氨酶的催化反应^[11]^[12]。

激活诱导性胞苷脱氨酶最早于1999年由日本免疫学家本庶佑发现^[13]，此酵素在免疫系统中有重要功能，B细胞在淋巴结的生发中心进行亲和力成熟（英语：affinity maturation）的过程中，催化C脱氨转为U的反应以造成DNA断裂，促进体细胞高频突变、免疫球蛋白类型转换和基因转换等增加抗体多样性的重要机制^[14]。较新的研究显示除B细胞外还有其他组织有表现激活诱导性胞苷脱氨酶，且除催化C-U转换之外，激活诱导性胞苷脱氨酶还可催化5-甲基胞嘧啶脱氨转为胸腺嘧啶（T），因而有去甲基酶（英语：Demethylase）的功能，可能参与基因的表观遗传学调控^[15]^[16]。

B细胞中有数种调控激活诱导性胞苷脱氨酶活性的机制，例如此蛋白上有许多可能调控其活性的磷酸化位点^[14]。此蛋白的表现异常与数种疾病有关，此基因的缺乏会导致第二型高免疫球蛋白M综合征（英语：Hyper-IgM syndrome type 2）^[17]，其过度表现则可能与数种B细胞淋巴瘤有关^[14]^[18]。

参考文献

^ 與活化誘導胞苷脫氨酶相關的疾病；在維基數據上查看/編輯參考.
^ ^2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000111732 - Ensembl, May 2017
^ ^3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000040627 - 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.
^ Entrez Gene: AICDA activation-induced cytidine deaminase.
^ Petersen-Mahrt, Svend K.; Harris, Reuben S.; Neuberger, Michael S. AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature. 2002-07-04, 418 (6893): 99–103 [2021-04-29]. ISSN 0028-0836. PMID 12097915. doi:10.1038/nature00862. （原始内容存档于2021-02-05）.
^ Q9GZX7 (AICDA_HUMAN). [26 January 2013]. （原始内容存档于2021-06-04）.
^ Pilzecker B, Jacobs H. Mutating for Good: DNA Damage Responses During Somatic Hypermutation.. Front Immunol. 2019, 10: 438. PMC 6423074  . PMID 30915081. doi:10.3389/fimmu.2019.00438.
^ Maul RW, Gearhart PJ. AID and somatic hypermutation.. Adv Immunol. 2010, 105: 159–91. PMC 2954419  . PMID 20510733. doi:10.1016/S0065-2776(10)05006-6.
^ Senavirathne G, Bertram JG, Jaszczur M, Chaurasiya KR, Pham P, Mak CH; et al. Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution.. Nat Commun. 2015, 6: 10209. PMC 4703863  . PMID 26681117. doi:10.1038/ncomms10209.
^ Ramiro AR, Stavropoulos P, Jankovic M, Nussenzweig MC. Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand.. Nat Immunol. 2003, 4 (5): 452–6. PMID 12692548. doi:10.1038/ni920.
^ Muramatsu M, Sankaranand VS, Anant S, Sugai M, Kinoshita K, Davidson NO; et al. Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells.. J Biol Chem. 1999, 274 (26): 18470–6. PMID 10373455. doi:10.1074/jbc.274.26.18470.
^ ^14.0 ^14.1 ^14.2 Robbiani DF, Nussenzweig MC. Chromosome translocation, B cell lymphoma, and activation-induced cytidine deaminase.. Annu Rev Pathol. 2013, 8: 79–103. PMID 22974238. doi:10.1146/annurev-pathol-020712-164004.
^ Morgan HD, Dean W, Coker HA, Reik W, Petersen-Mahrt SK. Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming.. J Biol Chem. 2004, 279 (50): 52353–60. PMID 15448152. doi:10.1074/jbc.M407695200.
^ Dominguez PM, Shaknovich R. Epigenetic function of activation-induced cytidine deaminase and its link to lymphomagenesis.. Front Immunol. 2014, 5: 642. PMC 4270259  . PMID 25566255. doi:10.3389/fimmu.2014.00642.
^ Luo Z, Ronai D, Scharff MD. The role of activation-induced cytidine deaminase in antibody diversification, immunodeficiency, and B-cell malignancies. J. Allergy Clin. Immunol. 2004, 114 (4): 726–35; quiz 736. PMID 15480307. doi:10.1016/j.jaci.2004.07.049.
^ Lenz G, Staudt LM. Aggressive Lymphomas. N Engl J Med. 2010, 362 (15): 1417–29. PMC 7316377  . PMID 20393178. doi:10.1056/NEJMra0807082.

[1] 與活化誘導胞苷脫氨酶相關的疾病；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-2] 2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000111732 - Ensembl, May 2017

[refGRCm38Ensembl-3] 3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000040627 - Ensembl, May 2017

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

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

[entrez-6] Entrez Gene: AICDA activation-induced cytidine deaminase.

[7] Petersen-Mahrt, Svend K.; Harris, Reuben S.; Neuberger, Michael S. AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature. 2002-07-04, 418 (6893): 99–103 [2021-04-29]. ISSN 0028-0836. PMID 12097915. doi:10.1038/nature00862. （原始内容存档于2021-02-05）.

[8] Q9GZX7 (AICDA_HUMAN). [26 January 2013]. （原始内容存档于2021-06-04）.

[pmid30915081-9] Pilzecker B, Jacobs H. Mutating for Good: DNA Damage Responses During Somatic Hypermutation.. Front Immunol. 2019, 10: 438. PMC 6423074  . PMID 30915081. doi:10.3389/fimmu.2019.00438.

[pmid20510733-10] Maul RW, Gearhart PJ. AID and somatic hypermutation.. Adv Immunol. 2010, 105: 159–91. PMC 2954419  . PMID 20510733. doi:10.1016/S0065-2776(10)05006-6.

[pmid26681117-11] Senavirathne G, Bertram JG, Jaszczur M, Chaurasiya KR, Pham P, Mak CH; et al. Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution.. Nat Commun. 2015, 6: 10209. PMC 4703863  . PMID 26681117. doi:10.1038/ncomms10209.

[pmid12692548-12] Ramiro AR, Stavropoulos P, Jankovic M, Nussenzweig MC. Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand.. Nat Immunol. 2003, 4 (5): 452–6. PMID 12692548. doi:10.1038/ni920.

[pmid10373455-13] Muramatsu M, Sankaranand VS, Anant S, Sugai M, Kinoshita K, Davidson NO; et al. Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells.. J Biol Chem. 1999, 274 (26): 18470–6. PMID 10373455. doi:10.1074/jbc.274.26.18470.

[pmid22974238-14] 14.0 ^14.1 ^14.2 Robbiani DF, Nussenzweig MC. Chromosome translocation, B cell lymphoma, and activation-induced cytidine deaminase.. Annu Rev Pathol. 2013, 8: 79–103. PMID 22974238. doi:10.1146/annurev-pathol-020712-164004.

[pmid15448152-15] Morgan HD, Dean W, Coker HA, Reik W, Petersen-Mahrt SK. Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming.. J Biol Chem. 2004, 279 (50): 52353–60. PMID 15448152. doi:10.1074/jbc.M407695200.

[pmid25566255-16] Dominguez PM, Shaknovich R. Epigenetic function of activation-induced cytidine deaminase and its link to lymphomagenesis.. Front Immunol. 2014, 5: 642. PMC 4270259  . PMID 25566255. doi:10.3389/fimmu.2014.00642.

[pmid15480307-17] Luo Z, Ronai D, Scharff MD. The role of activation-induced cytidine deaminase in antibody diversification, immunodeficiency, and B-cell malignancies. J. Allergy Clin. Immunol. 2004, 114 (4): 726–35; quiz 736. PMID 15480307. doi:10.1016/j.jaci.2004.07.049.

[18] Lenz G, Staudt LM. Aggressive Lymphomas. N Engl J Med. 2010, 362 (15): 1417–29. PMC 7316377  . PMID 20393178. doi:10.1056/NEJMra0807082.

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