AICDA_HUMAN
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 03-AUG-2022, entry version 178.
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 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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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). Interacts (via its NLS) with KPNA1. Interacts with
CC PKA/PRKACA and PRKAR1A/PKR1 (PubMed:16387847). Interacts with TRIM28
CC and NCL (By similarity). Interacts with SUPT6H (PubMed:21518874).
CC Interacts with RNF126 (PubMed:23277564). Directly interacts with
CC MCM3AP; this interaction may favor AICDA recruitment to immunoglobulin
CC variable region genes, hence promoting somatic hypermutations
CC (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 -!- 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}. Cytoplasm
CC {ECO:0000269|PubMed:18722174, ECO:0000269|PubMed:21385873,
CC ECO:0000269|PubMed:23166356}. Note=Predominantly cytoplasmic
CC (PubMed:21385873). In the presence of MCM3AP/GANP, relocalizes to the
CC nucleus (By similarity). {ECO:0000250|UniProtKB:Q9WVE0,
CC 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/";
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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; 56.
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; Q9GZX7; -.
DR PeptideAtlas; Q9GZX7; -.
DR PRIDE; Q9GZX7; -.
DR ProteomicsDB; 67301; -.
DR ProteomicsDB; 80168; -. [Q9GZX7-1]
DR Antibodypedia; 6178; 440 antibodies from 43 providers.
DR DNASU; 57379; -.
DR Ensembl; ENST00000229335.11; ENSP00000229335.6; ENSG00000111732.11. [Q9GZX7-1]
DR Ensembl; ENST00000537228.5; ENSP00000445691.1; ENSG00000111732.11. [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 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; AARLYFC; -.
DR PhylomeDB; Q9GZX7; -.
DR TreeFam; TF331356; -.
DR BRENDA; 3.5.4.38; 2681.
DR PathwayCommons; Q9GZX7; -.
DR SignaLink; Q9GZX7; -.
DR SIGNOR; Q9GZX7; -.
DR BioGRID-ORCS; 57379; 7 hits in 1063 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 92 other tissues.
DR ExpressionAtlas; Q9GZX7; baseline and differential.
DR Genevisible; Q9GZX7; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
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 assembly; 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:0010529; P:negative regulation of transposition; 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 InterPro; IPR016192; APOBEC/CMP_deaminase_Zn-bd.
DR InterPro; IPR002125; CMP_dCMP_dom.
DR InterPro; IPR016193; Cytidine_deaminase-like.
DR SUPFAM; SSF53927; SSF53927; 1.
DR PROSITE; PS00903; CYT_DCMP_DEAMINASES_1; 1.
DR PROSITE; PS51747; CYT_DCMP_DEAMINASES_2; 1.
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; unknown pathological significance;
FT loss of 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; unknown pathological 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; unknown pathological
FT 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
