活化诱导性胞苷脱氨酶

活化诱导性胞苷脱氨酶(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,接著可能由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活化诱导性胞苷脱氨酶的催化反应[11][12]

活化诱导胞苷脱氨酶
已知的结构
PDB直系同源搜索: PDBe RCSB
识别号
别名AICDA;, AID, ARP2, CDA2, HEL-S-284, HIGM2, activation-induced cytidine deaminase, activation induced cytidine deaminase
外部IDOMIM605257 MGI1342279 HomoloGene7623 GeneCardsAICDA
相关疾病
第二型高免疫球蛋白M症候群[1]
基因位置(人类
12号染色体
染色体12号染色体[2]
12号染色体
活化诱导胞苷脱氨酶的基因位置
活化诱导胞苷脱氨酶的基因位置
基因座12p13.31起始8,602,155 bp[2]
终止8,613,242 bp[2]
RNA表达模式
查阅更多表达数据
直系同源
物种人类小鼠
Entrez
Ensembl
UniProt
mRNA​序列

​NM_020661
​NM_001330343

NM_009645

蛋白序列

NP_001317272
​NP_065712

NP_033775

基因位置​(UCSC)Chr 12: 8.6 – 8.61 MbChr 6: 122.53 – 122.54 Mb
PubMed​查找[4][5]
维基数据
查看/编辑人类查看/编辑小鼠

活化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细胞淋巴结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,促进体细胞超突变免疫球蛋白类型转换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活化诱导性胞苷脱氨酶,且除催化C-U转换之外,活化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细胞中有数种调控活化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症候群英语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

编辑
  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. 
  2. ^ 2.0 2.1 2.2 GRCh38: Ensembl release 89: ENSG00000111732 - Ensembl, May 2017
  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. 
  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). 
  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  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.