ID AICDA_MOUSE Reviewed; 198 AA.
AC Q9WVE0;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 27-MAR-2024, entry version 155.
DE RecName: Full=Single-stranded DNA cytosine deaminase;
DE EC=3.5.4.38 {ECO:0000269|PubMed:12692563, ECO:0000269|PubMed:23803409};
DE AltName: Full=Activation-induced cytidine deaminase;
DE Short=AID;
DE AltName: Full=Cytidine aminohydrolase;
GN Name=Aicda; Synonyms=Aid;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10373455; DOI=10.1074/jbc.274.26.18470;
RA Muramatsu M., Sankaranand V.S., Anant S., Sugai M., Kinoshita K.,
RA Davidson N.O., Honjo T.;
RT "Specific expression of activation-induced cytidine deaminase (AID), a
RT novel member of the RNA-editing deaminase family in germinal center B
RT cells.";
RL J. Biol. Chem. 274:18470-18476(1999).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-56 AND GLU-58.
RX PubMed=12692563; DOI=10.1038/nature01574;
RA Chaudhuri J., Tian M., Khuong C., Chua K., Pinaud E., Alt F.W.;
RT "Transcription-targeted DNA deamination by the AID antibody diversification
RT enzyme.";
RL Nature 422:726-730(2003).
RN [3]
RP INTERACTION WITH MCM3AP, MUTAGENESIS OF ASP-143, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
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 [4]
RP INTERACTION WITH SUPT6H; TRIM28 AND NCL.
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP PHE-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).
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. May also play a role in the
CC epigenetic regulation of gene expression by participating in DNA
CC demethylation. {ECO:0000269|PubMed:12692563,
CC ECO:0000269|PubMed:23803409}.
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:12692563, ECO:0000269|PubMed:23803409};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9GZX7};
CC -!- SUBUNIT: Interacts with CTNNBL1; the interaction is important for the
CC immunoglobulin switch activity of AICDA. Interacts (via its NLS) with
CC KPNA1. Interacts with PKA/PRKACA and PRKAR1A/PKR1 (By similarity).
CC Interacts with SUPT6H, TRIM28 and NCL. Directly interacts with
CC MCM3AP/GANP; this interaction may favor AICDA recruitment to
CC immunoglobulin variable region genes, hence promoting somatic
CC hypermutations (PubMed:20507984). {ECO:0000250|UniProtKB:Q9GZX7,
CC ECO:0000269|PubMed:20507984, ECO:0000269|PubMed:21518874}.
CC -!- INTERACTION:
CC Q9WVE0; Q91Z31: Ptbp2; NbExp=4; IntAct=EBI-3835567, EBI-647632;
CC Q9WVE0; Q64511: Top2b; NbExp=3; IntAct=EBI-3835567, EBI-2325586;
CC Q9WVE0; P24522: GADD45A; Xeno; NbExp=3; IntAct=EBI-3835567, EBI-448167;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20507984}. Cytoplasm
CC {ECO:0000269|PubMed:20507984, ECO:0000269|PubMed:23803409}.
CC Note=Predominantly cytoplasmic. In the presence of MCM3AP/GANP,
CC relocalizes to the nucleus. {ECO:0000269|PubMed:20507984}.
CC -!- TISSUE SPECIFICITY: Expressed in germinal center B-cells (at protein
CC level). {ECO:0000269|PubMed:20507984}.
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 (By similarity). {ECO:0000250}.
CC -!- PTM: Probably monoubiquitinated on several residues by RNF126.
CC {ECO:0000250|UniProtKB:Q9GZX7}.
CC -!- SIMILARITY: Belongs to the cytidine and deoxycytidylate deaminase
CC family. {ECO:0000305}.
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; AF132979; AAD41793.1; -; mRNA.
DR CCDS; CCDS20497.1; -.
DR RefSeq; NP_033775.1; NM_009645.2.
DR AlphaFoldDB; Q9WVE0; -.
DR SMR; Q9WVE0; -.
DR BioGRID; 198040; 5.
DR DIP; DIP-48714N; -.
DR IntAct; Q9WVE0; 54.
DR MINT; Q9WVE0; -.
DR STRING; 10090.ENSMUSP00000040524; -.
DR iPTMnet; Q9WVE0; -.
DR PhosphoSitePlus; Q9WVE0; -.
DR PaxDb; 10090-ENSMUSP00000040524; -.
DR Antibodypedia; 6178; 481 antibodies from 43 providers.
DR DNASU; 11628; -.
DR Ensembl; ENSMUST00000043301.14; ENSMUSP00000040524.8; ENSMUSG00000040627.15.
DR GeneID; 11628; -.
DR KEGG; mmu:11628; -.
DR UCSC; uc009dpj.1; mouse.
DR AGR; MGI:1342279; -.
DR CTD; 57379; -.
DR MGI; MGI:1342279; Aicda.
DR VEuPathDB; HostDB:ENSMUSG00000040627; -.
DR eggNOG; KOG4075; Eukaryota.
DR GeneTree; ENSGT00940000158731; -.
DR HOGENOM; CLU_080056_4_0_1; -.
DR InParanoid; Q9WVE0; -.
DR OMA; HCYRITW; -.
DR OrthoDB; 5355962at2759; -.
DR PhylomeDB; Q9WVE0; -.
DR TreeFam; TF331356; -.
DR BRENDA; 3.5.4.38; 3474.
DR BioGRID-ORCS; 11628; 1 hit in 115 CRISPR screens.
DR PRO; PR:Q9WVE0; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9WVE0; Protein.
DR Bgee; ENSMUSG00000040627; Expressed in cumulus cell and 39 other cell types or tissues.
DR ExpressionAtlas; Q9WVE0; baseline and differential.
DR Genevisible; Q9WVE0; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000932; C:P-body; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0004126; F:cytidine deaminase activity; IDA:MGI.
DR GO; GO:0047844; F:deoxycytidine deaminase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:MGI.
DR GO; GO:0009972; P:cytidine deamination; IMP:UniProtKB.
DR GO; GO:0016554; P:cytidine to uridine editing; IBA:GO_Central.
DR GO; GO:0042742; P:defense response to bacterium; IMP:MGI.
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; ISS:UniProtKB.
DR GO; GO:0045190; P:isotype switching; IMP:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0090310; P:negative regulation of DNA methylation-dependent heterochromatin formation; ISS: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; ISO:MGI.
DR GO; GO:0016445; P:somatic diversification of immunoglobulins; ISO:MGI.
DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; ISS: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.
PE 1: Evidence at protein level;
KW Cytoplasm; Hydrolase; Metal-binding; mRNA processing; Nucleus;
KW Phosphoprotein; Reference proteome; Ubl conjugation; Zinc.
FT CHAIN 1..198
FT /note="Single-stranded DNA cytosine deaminase"
FT /id="PRO_0000171688"
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:0000250|UniProtKB:Q9GZX7"
FT REGION 39..42
FT /note="Important for interaction with CTNNBL1"
FT /evidence="ECO:0000250|UniProtKB:Q9GZX7"
FT REGION 88..116
FT /note="Required for interaction with RNF126"
FT /evidence="ECO:0000250|UniProtKB:Q9GZX7"
FT MOTIF 1..30
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9GZX7"
FT MOTIF 183..198
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:Q9GZX7"
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:0000250|UniProtKB:Q9GZX7"
FT BINDING 87
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9GZX7"
FT BINDING 90
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9GZX7"
FT MOD_RES 27
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q9GZX7"
FT MOD_RES 38
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q9GZX7"
FT MUTAGEN 15
FT /note="F->L: Severely decreased cytidine deaminase
FT activity. Loss of mutagenic activity."
FT /evidence="ECO:0000269|PubMed:23803409"
FT MUTAGEN 56
FT /note="H->R: Loss of the cytidine deaminase activity; when
FT associated with Q-58."
FT /evidence="ECO:0000269|PubMed:12692563"
FT MUTAGEN 58
FT /note="E->Q: Loss of the cytidine deaminase activity; when
FT associated with R-56."
FT /evidence="ECO:0000269|PubMed:12692563"
FT MUTAGEN 143
FT /note="D->A: 10-fold decrease in MCM3AP-binding affinity,
FT loss of relocalization to the nucleus in the presence of
FT MCM3AP, decreased deamination activity to about 33% of the
FT wild-type protein."
FT /evidence="ECO:0000269|PubMed:20507984"
SQ SEQUENCE 198 AA; 24031 MW; 18A3BA10CA54BEB2 CRC64;
MDSLLMKQKK FLYHFKNVRW AKGRHETYLC YVVKRRDSAT SCSLDFGHLR NKSGCHVELL
FLRYISDWDL DPGRCYRVTW FTSWSPCYDC ARHVAEFLRW NPNLSLRIFT ARLYFCEDRK
AEPEGLRRLH RAGVQIGIMT FKDYFYCWNT FVENRERTFK AWEGLHENSV RLTRQLRRIL
LPLYEVDDLR DAFRMLGF
//
