活化誘導性胞苷脫氨酶

活化誘導胞苷脫氨酶
已知的結構
PDB	直系同源搜尋: PDBe RCSB
PDBID列表
	5JJ4
識別號
別名	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
相關疾病
	第二型高免疫球蛋白M綜合症
基因位置（人類）
染色體	12號染色體
終止	8,613,242 bp
基因位置（小鼠）
染色體	小鼠6號染色體
終止	122,541,139 bp
RNA表達模式
	查閱更多表達數據
基因本體
分子功能	• hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines; • 鋅離子結合; • 血漿蛋白結合; • 催化活性; • 水解酶活性; • 泛素蛋白連接酶結合; • 金屬離子結合; • cytidine deaminase activity; • 相同蛋白質結合; • RNA binding;
細胞組分	• 外切體複合物; • 細胞核; • 細胞質; • 處理小體; • 大分子複合體;
生物學過程	• 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; • 免疫球蛋白類型轉換; • 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
	維基數據
檢視/編輯人類	檢視/編輯小鼠

活化誘導性胞苷脫氨酶（Activation-induced cytidine deaminase，簡稱AID）是一種胞苷脫氨酶（英語：Cytidine deaminase），屬APOBEC（英語：APOBEC）脫氨酶家族，在人類基因組中由12號染色體上的AICDA基因編碼，大小約為24kDa^[6]，可催化胞苷（C）脫氨轉為尿苷（U）的反應，即將DNA上的C:G配對轉為U:G誤配，且因DNA複製時會將U視為T，最終會導致U:G轉為T:A的轉換突變^[7]^[8]。U:G誤配也可能被細胞中的鹼基切除修復（BER）或錯誤配對修復（MMR）機制修補，BER途徑中此誤配可被尿嘧啶DNA糖基酶（英語：Uracil-DNA glycosylase）（UDG）識別而切除，形成AP位點，接着可能由DNA聚合酶η（英語：DNA polymerase eta）等易誤（error-prone）的聚合酶隨機補上鹼基而完成修補（短補丁修復），或將下游數個鹼基由內切酶切除後再合成新的核苷酸以完成修補（長補丁修復）^[9]；MMR途徑中，U:G誤配則會被MutSα複合體識別而被切除，再由易誤的聚合酶隨機補上鹼基，兩種修復機制皆可能造成突變^[10]。DNA轉錄時暫時呈單股的狀態有利於活化誘導性胞苷脫氨酶的催化反應^[11]^[12]。

活化誘導性胞苷脫氨酶最早於1999年由日本免疫學家本庶佑發現^[13]，此酵素在免疫系統中有重要功能，B細胞在淋巴結的生發中心進行親和力成熟（英語：affinity maturation）的過程中，催化C脫氨轉為U的反應以造成DNA斷裂，促進體細胞超突變、免疫球蛋白類型轉換和基因轉換等增加抗體多樣性的重要機制^[14]。較新的研究顯示除B細胞外還有其他組織有表現活化誘導性胞苷脫氨酶，且除催化C-U轉換之外，活化誘導性胞苷脫氨酶還可催化5-甲基胞嘧啶脫氨轉為胸腺嘧啶（T），因而有去甲基酶（英語：Demethylase）的功能，可能參與基因的表觀遺傳學調控^[15]^[16]。

B細胞中有數種調控活化誘導性胞苷脫氨酶活性的機制，例如此蛋白上有許多可能調控其活性的磷酸化位點^[14]。此蛋白的表現異常與數種疾病有關，此基因的缺乏會導致第二型高免疫球蛋白M綜合症（英語：Hyper-IgM syndrome type 2）^[17]，其過度表現則可能與數種B細胞淋巴瘤有關^[14]^[18]。

參考文獻

^ 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. （原始內容存檔於2021-02-05）.
^ Q9GZX7 (AICDA_HUMAN). [26 January 2013]. （原始內容存檔於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. （原始內容存檔於2021-02-05）.

[8] Q9GZX7 (AICDA_HUMAN). [26 January 2013]. （原始內容存檔於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.

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[1]

[2]

[3]

[4]

[5]

[13]

[14]

[15]

[16]

[17]

[18]