ID AICDA_HUMAN Reviewed; 198 AA. AC Q9GZX7; Q6QJ81; Q8NFC1; DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 24-JAN-2024, entry version 186. DE RecName: Full=Single-stranded DNA cytosine deaminase; DE EC=3.5.4.38 {ECO:0000269|PubMed:18722174}; DE AltName: Full=Activation-induced cytidine deaminase; DE Short=AID; DE AltName: Full=Cytidine aminohydrolase; GN Name=AICDA; Synonyms=AID; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). RX PubMed=10950930; DOI=10.1006/geno.2000.6268; RA Muto T., Muramatsu M., Taniwaki M., Kinoshita K., Honjo T.; RT "Isolation, tissue distribution, and chromosomal localization of the human RT activation-induced cytidine deaminase (hAID) gene."; RL Genomics 68:85-88(2000). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND VARIANTS HIGM2 RP TRP-24; ARG-80; PRO-106; VAL-139 AND SER-151. RX PubMed=11007475; DOI=10.1016/s0092-8674(00)00079-9; RA Revy P., Muto T., Levy Y., Geissmann F., Plebani A., Sanal O., Catalan N., RA Forveille M., Dufourcq-Lagelouse R., Gennery A., Tezcan I., Ersoy F., RA Kayserili H., Ugazio A.G., Brousse N., Muramatsu M., Notarangelo L.D., RA Kinoshita K., Honjo T., Fischer A., Durandy A.; RT "Activation-induced cytidine deaminase (AID) deficiency causes the RT autosomal recessive form of the Hyper-IgM syndrome (HIGM2)."; RL Cell 102:565-575(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=12202747; DOI=10.1073/pnas.192442899; RA Martin A., Scharff M.D.; RT "Somatic hypermutation of the AID transgene in B and non-B cells."; RL Proc. Natl. Acad. Sci. U.S.A. 99:12304-12308(2002). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Roa S., Gonzalez-Sarmiento R.; RT "Intracellular localization of AID isoforms."; RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=B-cell; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP SUBCELLULAR LOCATION. RX PubMed=14769937; DOI=10.1073/pnas.0307335101; RA Ito S., Nagaoka H., Shinkura R., Begum N., Muramatsu M., Nakata M., RA Honjo T.; RT "Activation-induced cytidine deaminase shuttles between nucleus and RT cytoplasm like apolipoprotein B mRNA editing catalytic polypeptide 1."; RL Proc. Natl. Acad. Sci. U.S.A. 101:1975-1980(2004). RN [9] RP PHOSPHORYLATION AT THR-27 AND SER-38, INTERACTION WITH PRKACA AND PRKAR1A, RP AND MUTAGENESIS OF THR-27 AND SER-38. RX PubMed=16387847; DOI=10.1073/pnas.0509969103; RA Pasqualucci L., Kitaura Y., Gu H., Dalla-Favera R.; RT "PKA-mediated phosphorylation regulates the function of activation-induced RT deaminase (AID) in B cells."; RL Proc. Natl. Acad. Sci. U.S.A. 103:395-400(2006). RN [10] RP INTERACTION WITH CTNNBL1, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR RP LOCATION, PHOSPHORYLATION AT SER-38, IDENTIFICATION BY MASS SPECTROMETRY, RP AND MUTAGENESIS OF 39-ALA--PHE-42 AND SER-38. RX PubMed=18722174; DOI=10.1016/j.molcel.2008.07.009; RA Conticello S.G., Ganesh K., Xue K., Lu M., Rada C., Neuberger M.S.; RT "Interaction between antibody-diversification enzyme AID and spliceosome- RT associated factor CTNNBL1."; RL Mol. Cell 31:474-484(2008). RN [11] RP INTERACTION WITH MCM3AP. RX PubMed=20507984; DOI=10.1074/jbc.m110.131441; RA Maeda K., Singh S.K., Eda K., Kitabatake M., Pham P., Goodman M.F., RA Sakaguchi N.; RT "GANP-mediated recruitment of activation-induced cytidine deaminase to cell RT nuclei and to immunoglobulin variable region DNA."; RL J. Biol. Chem. 285:23945-23953(2010). RN [12] RP FUNCTION IN DNA DEMETHYLATION. RX PubMed=21496894; DOI=10.1016/j.cell.2011.03.022; RA Guo J.U., Su Y., Zhong C., Ming G.L., Song H.; RT "Hydroxylation of 5-methylcytosine by TET1 promotes active DNA RT demethylation in the adult brain."; RL Cell 145:423-434(2011). RN [13] RP INTERACTION WITH CTNNBL1, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF RP LYS-10; VAL-18; ARG-19; TRP-20; ARG-50; ARG-112 AND PHE-193, AND RP CHARACTERIZATION OF VARIANT TRP-24. RX PubMed=21385873; DOI=10.1074/jbc.m110.208769; RA Ganesh K., Adam S., Taylor B., Simpson P., Rada C., Neuberger M.; RT "CTNNBL1 is a novel nuclear localization sequence-binding protein that RT recognizes RNA-splicing factors CDC5L and Prp31."; RL J. Biol. Chem. 286:17091-17102(2011). RN [14] RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF THR-27. RX PubMed=21659520; DOI=10.1074/jbc.m111.235721; RA Demorest Z.L., Li M., Harris R.S.; RT "Phosphorylation directly regulates the intrinsic DNA cytidine deaminase RT activity of activation-induced deaminase and APOBEC3G protein."; RL J. Biol. Chem. 286:26568-26575(2011). RN [15] RP FUNCTION, AND INTERACTION WITH SUPT6H. RX PubMed=21518874; DOI=10.1073/pnas.1104423108; RA Okazaki I.M., Okawa K., Kobayashi M., Yoshikawa K., Kawamoto S., RA Nagaoka H., Shinkura R., Kitawaki Y., Taniguchi H., Natsume T., Iemura S., RA Honjo T.; RT "Histone chaperone Spt6 is required for class switch recombination but not RT somatic hypermutation."; RL Proc. Natl. Acad. Sci. U.S.A. 108:7920-7925(2011). RN [16] RP INDUCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=23166356; DOI=10.1084/jem.20121387; RA Basso K., Schneider C., Shen Q., Holmes A.B., Setty M., Leslie C., RA Dalla-Favera R.; RT "BCL6 positively regulates AID and germinal center gene expression via RT repression of miR-155."; RL J. Exp. Med. 209:2455-2465(2012). RN [17] RP INTERACTION WITH RNF126, AND UBIQUITINATION BY RNF126. RX PubMed=23277564; DOI=10.1073/pnas.1214538110; RA Delker R.K., Zhou Y., Strikoudis A., Stebbins C.E., Papavasiliou F.N.; RT "Solubility-based genetic screen identifies RING finger protein 126 as an RT E3 ligase for activation-induced cytidine deaminase."; RL Proc. Natl. Acad. Sci. U.S.A. 110:1029-1034(2013). RN [18] RP INTERACTION WITH CTNNBL1, AND SUBCELLULAR LOCATION. RX PubMed=32484799; DOI=10.1172/jci131297; RA Kuhny M., Forbes L.R., Cakan E., Vega-Loza A., Kostiuk V., Dinesh R.K., RA Glauzy S., Stray-Pedersen A., Pezzi A.E., Hanson I.C., Vargas-Hernandez A., RA Xu M.L., Coban-Akdemir Z.H., Jhangiani S.N., Muzny D.M., Gibbs R.A., RA Lupski J.R., Chinn I.K., Schatz D.G., Orange J.S., Meffre E.; RT "Disease-associated CTNNBL1 mutation impairs somatic hypermutation by RT decreasing nuclear AID."; RL J. Clin. Invest. 130:4411-4422(2020). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) OF 23-183 IN COMPLEX WITH ZINC. RX PubMed=27258794; DOI=10.1016/j.dnarep.2016.05.029; RA Pham P., Afif S.A., Shimoda M., Maeda K., Sakaguchi N., Pedersen L.C., RA Goodman M.F.; RT "Structural analysis of the activation-induced deoxycytidine deaminase RT required in immunoglobulin diversification."; RL DNA Repair 43:48-56(2016). RN [20] RP VARIANT CYS-25. RX PubMed=11544457; DOI=10.1067/mai.2001.117456; RA Noguchi E., Shibasaki M., Inudou M., Kamioka M., Yokouchi Y., RA Yamakawa-Kobayashi K., Hamaguchi H., Matsui A., Arinami T.; RT "Association between a new polymorphism in the activation-induced cytidine RT deaminase gene and atopic asthma and the regulation of total serum IgE RT levels."; RL J. Allergy Clin. Immunol. 108:382-386(2001). RN [21] RP VARIANTS HIGM2 TRP-24; TYR-56; ARG-80; ARG-87; PRO-106; VAL-139; SER-151 RP AND SER-174. RX PubMed=14962793; DOI=10.1016/j.clim.2003.10.007; RA Quartier P., Bustamante J., Sanal O., Plebani A., Debre M., Deville A., RA Litzman J., Levy J., Fermand J.P., Lane P., Horneff G., Aksu G., Yalcin I., RA Davies G., Tezcan I., Ersoy F., Catalan N., Imai K., Fischer A., RA Durandy A.; RT "Clinical, immunologic and genetic analysis of 29 patients with autosomal RT recessive hyper-IgM syndrome due to activation-induced cytidine deaminase RT deficiency."; RL Clin. Immunol. 110:22-29(2004). RN [22] RP VARIANT HIGM2 LEU-15. RX PubMed=23803409; DOI=10.1016/j.clim.2013.05.017; RA Caratao N., Cortesao C.S., Reis P.H., Freitas R.F., Jacob C.M., RA Pastorino A.C., Carneiro-Sampaio M., Barreto V.M.; RT "A novel activation-induced cytidine deaminase (AID) mutation in Brazilian RT patients with hyper-IgM type 2 syndrome."; RL Clin. Immunol. 148:279-286(2013). RN [23] RP VARIANTS HIGM2 HIS-31 AND PRO-130. RX PubMed=26545377; DOI=10.1007/s00251-015-0878-6; RA Ouadani H., Ben-Mustapha I., Ben-ali M., Ben-khemis L., Largueche B., RA Boussoffara R., Maalej S., Fetni I., Hassayoun S., Mahfoudh A., RA Mellouli F., Yalaoui S., Masmoudi H., Bejaoui M., Barbouche M.R.; RT "Novel and recurrent AID mutations underlie prevalent autosomal recessive RT form of HIGM in consanguineous patients."; RL Immunogenetics 68:19-28(2016). RN [24] RP CHARACTERIZATION OF VARIANTS HIGM2 TYR-56 AND PRO-130, AND FUNCTION. RX PubMed=27716525; DOI=10.1016/j.molimm.2016.09.025; RA Ouadani H., Ben-Mustapha I., Ben-Ali M., Largueche B., Jovanic T., RA Garcia S., Arcangioli B., Elloumi-Zghal H., Fathallah D., Hachicha M., RA Masmoudi H., Rougeon F., Barbouche M.R.; RT "Activation induced cytidine deaminase mutant (AID-His130Pro) from Hyper RT IgM 2 patient retained mutagenic activity on SHM artificial substrate."; RL Mol. Immunol. 79:77-82(2016). CC -!- FUNCTION: Single-stranded DNA-specific cytidine deaminase. Involved in CC somatic hypermutation (SHM), gene conversion, and class-switch CC recombination (CSR) in B-lymphocytes by deaminating C to U during CC transcription of Ig-variable (V) and Ig-switch (S) region DNA. Required CC for several crucial steps of B-cell terminal differentiation necessary CC for efficient antibody responses (PubMed:18722174, PubMed:21385873, CC PubMed:21518874, PubMed:27716525). May also play a role in the CC epigenetic regulation of gene expression by participating in DNA CC demethylation (PubMed:21496894). {ECO:0000269|PubMed:18722174, CC ECO:0000269|PubMed:21385873, ECO:0000269|PubMed:21496894, CC ECO:0000269|PubMed:21518874, ECO:0000269|PubMed:27716525}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 2'-deoxycytidine in single-stranded DNA + H(+) + H2O = a 2'- CC deoxyuridine in single-stranded DNA + NH4(+); Xref=Rhea:RHEA:50948, CC Rhea:RHEA-COMP:12846, Rhea:RHEA-COMP:12847, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:85452, CC ChEBI:CHEBI:133902; EC=3.5.4.38; CC Evidence={ECO:0000269|PubMed:18722174}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:27258794}; CC -!- SUBUNIT: Interacts with CTNNBL1; the interaction is important for the CC immunoglobulin switch activity of AICDA (PubMed:18722174, CC PubMed:21385873, PubMed:32484799). Interacts (via its NLS) with KPNA1. CC Interacts with PKA/PRKACA and PRKAR1A/PKR1 (PubMed:16387847). Interacts CC with TRIM28 and NCL (By similarity). Interacts with SUPT6H CC (PubMed:21518874). Interacts with RNF126 (PubMed:23277564). Directly CC interacts with MCM3AP; this interaction may favor AICDA recruitment to CC immunoglobulin variable region genes, hence promoting somatic CC hypermutations (PubMed:20507984). {ECO:0000250|UniProtKB:Q9WVE0, CC ECO:0000269|PubMed:16387847, ECO:0000269|PubMed:18722174, CC ECO:0000269|PubMed:20507984, ECO:0000269|PubMed:21385873, CC ECO:0000269|PubMed:21518874, ECO:0000269|PubMed:23277564, CC ECO:0000269|PubMed:32484799}. CC -!- INTERACTION: CC Q9GZX7; Q9GZX7: AICDA; NbExp=2; IntAct=EBI-3834328, EBI-3834328; CC Q9GZX7; P31689: DNAJA1; NbExp=6; IntAct=EBI-3834328, EBI-347834; CC Q9GZX7; O60884: DNAJA2; NbExp=3; IntAct=EBI-3834328, EBI-352957; CC Q9GZX7; P24522: GADD45A; NbExp=5; IntAct=EBI-3834328, EBI-448167; CC Q9GZX7; P11142: HSPA8; NbExp=2; IntAct=EBI-3834328, EBI-351896; CC Q9GZX7; P52294: KPNA1; NbExp=2; IntAct=EBI-3834328, EBI-358383; CC Q9GZX7; O00505: KPNA3; NbExp=2; IntAct=EBI-3834328, EBI-358297; CC Q9GZX7; O15131: KPNA5; NbExp=2; IntAct=EBI-3834328, EBI-540602; CC Q9GZX7; P17612: PRKACA; NbExp=3; IntAct=EBI-3834328, EBI-476586; CC Q9GZX7; P10644: PRKAR1A; NbExp=5; IntAct=EBI-3834328, EBI-476431; CC Q9GZX7; Q13569: TDG; NbExp=5; IntAct=EBI-3834328, EBI-348333; CC Q9GZX7; Q784Z8: C; Xeno; NbExp=2; IntAct=EBI-3834328, EBI-11666471; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21385873, CC ECO:0000269|PubMed:32484799}. Cytoplasm, cytosol CC {ECO:0000269|PubMed:18722174, ECO:0000269|PubMed:21385873, CC ECO:0000269|PubMed:23166356, ECO:0000269|PubMed:32484799}. CC Note=Predominantly cytosolic (PubMed:21385873). In the presence of CC MCM3AP/GANP, relocalizes to the nucleus (By similarity). CC {ECO:0000250|UniProtKB:Q9WVE0, ECO:0000269|PubMed:21385873}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9GZX7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9GZX7-2; Sequence=VSP_047803; CC -!- TISSUE SPECIFICITY: Strongly expressed in lymph nodes and tonsils. CC {ECO:0000269|PubMed:23166356}. CC -!- INDUCTION: Negatively regulated by microRNA-155 (miR-155). CC {ECO:0000269|PubMed:23166356}. CC -!- PTM: Ser-38 is the major site whereas Thr-27 is the minor site of CC phosphorylation. Phosphorylation regulates its class-switch CC recombination activity. {ECO:0000269|PubMed:16387847, CC ECO:0000269|PubMed:18722174}. CC -!- PTM: Probably monoubiquitinated on several residues by RNF126. CC {ECO:0000269|PubMed:23277564}. CC -!- DISEASE: Immunodeficiency with hyper-IgM 2 (HIGM2) [MIM:605258]: A rare CC immunodeficiency syndrome characterized by normal or elevated serum IgM CC levels with absence of IgG, IgA, and IgE. It results in a profound CC susceptibility to bacterial infections. {ECO:0000269|PubMed:11007475, CC ECO:0000269|PubMed:14962793, ECO:0000269|PubMed:23803409, CC ECO:0000269|PubMed:26545377, ECO:0000269|PubMed:27716525}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the cytidine and deoxycytidylate deaminase CC family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=AICDAbase; Note=AICDA mutation db; CC URL="http://structure.bmc.lu.se/idbase/AICDAbase/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB040431; BAB12721.1; -; mRNA. DR EMBL; AB040430; BAB12720.1; -; Genomic_DNA. DR EMBL; AF529819; AAM95406.1; -; mRNA. DR EMBL; AY536516; AAS92920.1; -; mRNA. DR EMBL; BT007402; AAP36066.1; -; mRNA. DR EMBL; AC092184; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC006296; AAH06296.1; -; mRNA. DR CCDS; CCDS41747.1; -. [Q9GZX7-1] DR CCDS; CCDS81662.1; -. [Q9GZX7-2] DR RefSeq; NP_001317272.1; NM_001330343.1. [Q9GZX7-2] DR RefSeq; NP_065712.1; NM_020661.3. [Q9GZX7-1] DR PDB; 5JJ4; X-ray; 2.81 A; A/B/C=23-183. DR PDB; 5W0R; X-ray; 2.40 A; A/B=13-181. DR PDB; 5W0U; X-ray; 2.90 A; A/B=13-181. DR PDB; 5W0Z; X-ray; 3.61 A; A/B=13-181. DR PDB; 5W1C; X-ray; 3.18 A; A/B=5-181. DR PDBsum; 5JJ4; -. DR PDBsum; 5W0R; -. DR PDBsum; 5W0U; -. DR PDBsum; 5W0Z; -. DR PDBsum; 5W1C; -. DR AlphaFoldDB; Q9GZX7; -. DR SMR; Q9GZX7; -. DR BioGRID; 121497; 71. DR DIP; DIP-48519N; -. DR ELM; Q9GZX7; -. DR IntAct; Q9GZX7; 31. DR MINT; Q9GZX7; -. DR STRING; 9606.ENSP00000229335; -. DR iPTMnet; Q9GZX7; -. DR PhosphoSitePlus; Q9GZX7; -. DR BioMuta; AICDA; -. DR DMDM; 23813666; -. DR MassIVE; Q9GZX7; -. DR MaxQB; Q9GZX7; -. DR PaxDb; 9606-ENSP00000229335; -. DR PeptideAtlas; Q9GZX7; -. DR ProteomicsDB; 67301; -. DR ProteomicsDB; 80168; -. [Q9GZX7-1] DR Antibodypedia; 6178; 481 antibodies from 43 providers. DR DNASU; 57379; -. DR Ensembl; ENST00000229335.11; ENSP00000229335.6; ENSG00000111732.12. [Q9GZX7-1] DR Ensembl; ENST00000537228.6; ENSP00000445691.1; ENSG00000111732.12. [Q9GZX7-2] DR GeneID; 57379; -. DR KEGG; hsa:57379; -. DR MANE-Select; ENST00000229335.11; ENSP00000229335.6; NM_020661.4; NP_065712.1. DR UCSC; uc001qur.3; human. [Q9GZX7-1] DR AGR; HGNC:13203; -. DR CTD; 57379; -. DR DisGeNET; 57379; -. DR GeneCards; AICDA; -. DR HGNC; HGNC:13203; AICDA. DR HPA; ENSG00000111732; Tissue enriched (lymphoid). DR MalaCards; AICDA; -. DR MIM; 605257; gene. DR MIM; 605258; phenotype. DR neXtProt; NX_Q9GZX7; -. DR OpenTargets; ENSG00000111732; -. DR Orphanet; 101089; Hyper-IgM syndrome type 2. DR PharmGKB; PA24644; -. DR VEuPathDB; HostDB:ENSG00000111732; -. DR eggNOG; KOG4075; Eukaryota. DR GeneTree; ENSGT00940000158731; -. DR InParanoid; Q9GZX7; -. DR OMA; HCYRITW; -. DR OrthoDB; 5355962at2759; -. DR PhylomeDB; Q9GZX7; -. DR TreeFam; TF331356; -. DR BRENDA; 3.5.4.38; 2681. DR PathwayCommons; Q9GZX7; -. DR Reactome; R-HSA-9821002; Chromatin modifications during the maternal to zygotic transition (MZT). DR SignaLink; Q9GZX7; -. DR SIGNOR; Q9GZX7; -. DR BioGRID-ORCS; 57379; 8 hits in 1141 CRISPR screens. DR ChiTaRS; AICDA; human. DR GeneWiki; AICDA; -. DR GenomeRNAi; 57379; -. DR Pharos; Q9GZX7; Tbio. DR PRO; PR:Q9GZX7; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q9GZX7; Protein. DR Bgee; ENSG00000111732; Expressed in buccal mucosa cell and 93 other cell types or tissues. DR ExpressionAtlas; Q9GZX7; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0000932; C:P-body; IBA:GO_Central. DR GO; GO:0032991; C:protein-containing complex; IPI:GO_Central. DR GO; GO:0004126; F:cytidine deaminase activity; IDA:UniProtKB. DR GO; GO:0047844; F:deoxycytidine deaminase activity; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0003723; F:RNA binding; IBA:GO_Central. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0030183; P:B cell differentiation; NAS:UniProtKB. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0016554; P:cytidine to uridine editing; IBA:GO_Central. DR GO; GO:0042742; P:defense response to bacterium; IEA:Ensembl. DR GO; GO:0051607; P:defense response to virus; IBA:GO_Central. DR GO; GO:0070383; P:DNA cytosine deamination; IBA:GO_Central. DR GO; GO:0080111; P:DNA demethylation; IDA:UniProtKB. DR GO; GO:0045190; P:isotype switching; IEA:Ensembl. DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW. DR GO; GO:0090310; P:negative regulation of DNA methylation-dependent heterochromatin formation; IDA:UniProtKB. DR GO; GO:0045869; P:negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; IBA:GO_Central. DR GO; GO:0033262; P:regulation of nuclear cell cycle DNA replication; IMP:UniProtKB. DR GO; GO:0016445; P:somatic diversification of immunoglobulins; IDA:UniProtKB. DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; IMP:UniProtKB. DR CDD; cd01283; cytidine_deaminase; 1. DR Gene3D; 3.40.140.10; Cytidine Deaminase, domain 2; 1. DR InterPro; IPR016192; APOBEC/CMP_deaminase_Zn-bd. DR InterPro; IPR013158; APOBEC_N. DR InterPro; IPR002125; CMP_dCMP_dom. DR InterPro; IPR016193; Cytidine_deaminase-like. DR PANTHER; PTHR13857; MRNA EDITING ENZYME; 1. DR PANTHER; PTHR13857:SF10; SINGLE-STRANDED DNA CYTOSINE DEAMINASE; 1. DR Pfam; PF08210; APOBEC_N; 1. DR SUPFAM; SSF53927; Cytidine deaminase-like; 1. DR PROSITE; PS00903; CYT_DCMP_DEAMINASES_1; 1. DR PROSITE; PS51747; CYT_DCMP_DEAMINASES_2; 1. DR Genevisible; Q9GZX7; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant; Hydrolase; KW Metal-binding; mRNA processing; Nucleus; Phosphoprotein; KW Reference proteome; Ubl conjugation; Zinc. FT CHAIN 1..198 FT /note="Single-stranded DNA cytosine deaminase" FT /id="PRO_0000171687" FT DOMAIN 23..129 FT /note="CMP/dCMP-type deaminase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083" FT REGION 2..26 FT /note="Interaction with SUPT6H" FT /evidence="ECO:0000269|PubMed:21518874" FT REGION 39..42 FT /note="Important for interaction with CTNNBL1" FT /evidence="ECO:0000269|PubMed:18722174" FT REGION 88..116 FT /note="Required for interaction with RNF126" FT /evidence="ECO:0000269|PubMed:23277564" FT MOTIF 1..30 FT /note="Bipartite nuclear localization signal" FT /evidence="ECO:0000269|PubMed:14769937" FT MOTIF 183..198 FT /note="Nuclear export signal" FT /evidence="ECO:0000269|PubMed:14769937" FT ACT_SITE 58 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:P0ABF6" FT BINDING 56 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:27258794" FT BINDING 87 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:27258794" FT BINDING 90 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:27258794" FT MOD_RES 27 FT /note="Phosphothreonine; by PKA" FT /evidence="ECO:0000269|PubMed:16387847" FT MOD_RES 38 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:16387847, FT ECO:0000269|PubMed:18722174" FT VAR_SEQ 143..152 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_047803" FT VARIANT 15 FT /note="F -> L (in HIGM2)" FT /evidence="ECO:0000269|PubMed:23803409" FT /id="VAR_077563" FT VARIANT 24 FT /note="R -> W (in HIGM2; completely abolishes nuclear FT import and interaction with CTNNBL1, diminishes interaction FT with KPNA1 and abolishes immunoglobulin class switching; FT dbSNP:rs104894324)" FT /evidence="ECO:0000269|PubMed:11007475, FT ECO:0000269|PubMed:14962793, ECO:0000269|PubMed:21385873" FT /id="VAR_013774" FT VARIANT 25 FT /note="R -> C (in dbSNP:rs1404944797)" FT /evidence="ECO:0000269|PubMed:11544457" FT /id="VAR_014091" FT VARIANT 31 FT /note="Y -> H (in HIGM2)" FT /evidence="ECO:0000269|PubMed:26545377" FT /id="VAR_077564" FT VARIANT 56 FT /note="H -> Y (in HIGM2; uncertain significance; loss of FT mutagenic activity)" FT /evidence="ECO:0000269|PubMed:14962793, FT ECO:0000269|PubMed:27716525" FT /id="VAR_077565" FT VARIANT 80 FT /note="W -> R (in HIGM2; dbSNP:rs104894320)" FT /evidence="ECO:0000269|PubMed:11007475, FT ECO:0000269|PubMed:14962793" FT /id="VAR_013775" FT VARIANT 87 FT /note="C -> R (in HIGM2; uncertain significance; FT dbSNP:rs762590894)" FT /evidence="ECO:0000269|PubMed:14962793" FT /id="VAR_077566" FT VARIANT 106 FT /note="L -> P (in HIGM2; dbSNP:rs104894321)" FT /evidence="ECO:0000269|PubMed:11007475, FT ECO:0000269|PubMed:14962793" FT /id="VAR_013776" FT VARIANT 130 FT /note="H -> P (in HIGM2; slightly decreased mutagenic FT activity)" FT /evidence="ECO:0000269|PubMed:26545377, FT ECO:0000269|PubMed:27716525" FT /id="VAR_077567" FT VARIANT 139 FT /note="M -> V (in HIGM2; dbSNP:rs104894322)" FT /evidence="ECO:0000269|PubMed:11007475, FT ECO:0000269|PubMed:14962793" FT /id="VAR_013777" FT VARIANT 151 FT /note="F -> S (in HIGM2; dbSNP:rs104894327)" FT /evidence="ECO:0000269|PubMed:11007475, FT ECO:0000269|PubMed:14962793" FT /id="VAR_013778" FT VARIANT 174 FT /note="R -> S (in HIGM2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:14962793" FT /id="VAR_077568" FT MUTAGEN 10 FT /note="K->A: Little effect on nuclear import; when FT associated with A-193. No effect on CTNNBL1 binding." FT /evidence="ECO:0000269|PubMed:21385873" FT MUTAGEN 18 FT /note="V->S: Greatly impaired nuclear import; when FT associated with V-19 and A-193. Reduced interaction with FT both CTNNBL1 and KPNA1, and abolishes immunoglobulin class FT switching; when associated with V-19." FT /evidence="ECO:0000269|PubMed:21385873" FT MUTAGEN 19 FT /note="R->V: Greatly impaired nuclear import; when FT associated with S-18 and A-193. Reduced interaction with FT both CTNNBL1 and KPNA1, and abolishes immunoglobulin class FT switching; when associated with S-18." FT /evidence="ECO:0000269|PubMed:21385873" FT MUTAGEN 20 FT /note="W->K: Impaired nuclear import; when associated with FT A-193. No effect on CTNNBL1 binding." FT /evidence="ECO:0000269|PubMed:21385873" FT MUTAGEN 27 FT /note="T->A: Loss of phosphorylation. No effect on cytidine FT deaminase activity. Impaired class-switch recombination FT activity." FT /evidence="ECO:0000269|PubMed:16387847, FT ECO:0000269|PubMed:21659520" FT MUTAGEN 27 FT /note="T->E: Phosphomimetic mutant which shows loss of FT cytidine deaminase activity and impaired class-switch FT recombination activity." FT /evidence="ECO:0000269|PubMed:16387847, FT ECO:0000269|PubMed:21659520" FT MUTAGEN 38 FT /note="S->A: Loss of phosphorylation. Impaired class-switch FT recombination activity. No effect on interaction with FT CTNNBL1." FT /evidence="ECO:0000269|PubMed:16387847, FT ECO:0000269|PubMed:18722174" FT MUTAGEN 38 FT /note="S->D: No effect on interaction with CTNNBL1." FT /evidence="ECO:0000269|PubMed:16387847, FT ECO:0000269|PubMed:18722174" FT MUTAGEN 39..42 FT /note="ATSF->GGQV: Greatly reduced interaction with CTNNBL1 FT but no effect on subcellular location, enzyme activity, FT ability to oligomerize nor on phosphorylation at Ser-38. FT Diminished antibody diversification." FT /evidence="ECO:0000269|PubMed:18722174" FT MUTAGEN 50 FT /note="R->G: Some reduced nuclear import; when associated FT with A-193." FT /evidence="ECO:0000269|PubMed:21385873" FT MUTAGEN 112 FT /note="R->D: Greatly reduced nuclear import; when FT associated with A-193." FT /evidence="ECO:0000269|PubMed:21385873" FT MUTAGEN 193 FT /note="F->A: Completely abolishes nuclear import; when FT associated with W-24 or D-112. Little affect on nuclear FT import; when associated with A-10. Greatly impaired nuclear FT import; when associated with K-20 or G-50. Almost FT completely abolishes nuclear import; when associated with FT S-18 and V-19." FT /evidence="ECO:0000269|PubMed:21385873" FT CONFLICT 119 FT /note="R -> H (in Ref. 3; AAM95406)" FT /evidence="ECO:0000305" FT HELIX 8..15 FT /evidence="ECO:0007829|PDB:5W1C" FT STRAND 18..20 FT /evidence="ECO:0007829|PDB:5W0U" FT STRAND 28..34 FT /evidence="ECO:0007829|PDB:5W0R" FT STRAND 36..40 FT /evidence="ECO:0007829|PDB:5W0R" FT STRAND 43..50 FT /evidence="ECO:0007829|PDB:5W0R" FT HELIX 57..66 FT /evidence="ECO:0007829|PDB:5W0R" FT STRAND 72..74 FT /evidence="ECO:0007829|PDB:5W0R" FT STRAND 76..84 FT /evidence="ECO:0007829|PDB:5W0R" FT HELIX 88..100 FT /evidence="ECO:0007829|PDB:5W0R" FT STRAND 104..112 FT /evidence="ECO:0007829|PDB:5W0R" FT TURN 117..119 FT /evidence="ECO:0007829|PDB:5W0R" FT HELIX 122..132 FT /evidence="ECO:0007829|PDB:5W0R" FT STRAND 135..138 FT /evidence="ECO:0007829|PDB:5W0R" FT HELIX 141..148 FT /evidence="ECO:0007829|PDB:5W0R" FT HELIX 165..179 FT /evidence="ECO:0007829|PDB:5W0R" SQ SEQUENCE 198 AA; 23954 MW; 3C27BB143DB184A9 CRC64; MDSLLMNRRK FLYQFKNVRW AKGRRETYLC YVVKRRDSAT SFSLDFGYLR NKNGCHVELL FLRYISDWDL DPGRCYRVTW FTSWSPCYDC ARHVADFLRG NPNLSLRIFT ARLYFCEDRK AEPEGLRRLH RAGVQIAIMT FKDYFYCWNT FVENHERTFK AWEGLHENSV RLSRQLRRIL LPLYEVDDLR DAFRTLGL //