ID AICDA_BOVIN Reviewed; 199 AA. AC Q2PT36; DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot. DT 24-JAN-2006, sequence version 1. DT 24-JAN-2024, entry version 84. DE RecName: Full=Single-stranded DNA cytosine deaminase; DE EC=3.5.4.38 {ECO:0000250|UniProtKB:Q9WVE0}; DE AltName: Full=Activation-induced cytidine deaminase; DE Short=AID; DE AltName: Full=Cytidine aminohydrolase; GN Name=AICDA; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Spleen; RX PubMed=19766322; DOI=10.1016/j.vetimm.2009.08.016; RA Verma S., Goldammer T., Aitken R.; RT "Cloning and expression of activation induced cytidine deaminase from Bos RT taurus."; RL Vet. Immunol. Immunopathol. 134:151-159(2010). 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:0000250|UniProtKB:Q9GZX7}. 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:0000250|UniProtKB:Q9WVE0}; 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. Interacts with CC SUPT6H, TRIM28 and NCL. Directly interacts with MCM3AP; this CC interaction may favor AICDA recruitment to immunoglobulin variable CC region genes, hence promoting somatic hypermutations (By similarity). CC {ECO:0000250|UniProtKB:Q9GZX7, ECO:0000250|UniProtKB:Q9WVE0}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9GZX7}. Cytoplasm CC {ECO:0000250|UniProtKB:Q9GZX7}. Note=Predominantly cytoplasmic. In the CC presence of MCM3AP/GANP, relocalizes to the nucleus. CC {ECO:0000250|UniProtKB:Q9WVE0}. CC -!- TISSUE SPECIFICITY: Expressed in lymph nodes, spleen and thymus. CC {ECO:0000269|PubMed:19766322}. 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; DQ303466; ABC46408.1; -; mRNA. DR RefSeq; NP_001033771.1; NM_001038682.1. DR AlphaFoldDB; Q2PT36; -. DR SMR; Q2PT36; -. DR STRING; 9913.ENSBTAP00000025096; -. DR PaxDb; 9913-ENSBTAP00000025096; -. DR GeneID; 539888; -. DR KEGG; bta:539888; -. DR CTD; 57379; -. DR eggNOG; KOG4075; Eukaryota. DR InParanoid; Q2PT36; -. DR OrthoDB; 5355962at2759; -. DR BRENDA; 3.5.4.38; 908. DR Proteomes; UP000009136; Unplaced. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0000932; C:P-body; IBA:GO_Central. DR GO; GO:0004126; F:cytidine deaminase activity; ISS:UniProtKB. DR GO; GO:0047844; F:deoxycytidine deaminase activity; IBA:GO_Central. DR GO; GO:0003723; F:RNA binding; IBA:GO_Central. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0009972; P:cytidine deamination; ISS:UniProtKB. DR GO; GO:0016554; P:cytidine to uridine editing; IBA:GO_Central. 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: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: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 2: Evidence at transcript level; KW Cytoplasm; Hydrolase; Metal-binding; mRNA processing; Nucleus; KW Phosphoprotein; Reference proteome; Ubl conjugation; Zinc. FT CHAIN 1..199 FT /note="Single-stranded DNA cytosine deaminase" FT /id="PRO_0000232719" FT DOMAIN 23..130 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 184..199 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" SQ SEQUENCE 199 AA; 24052 MW; 448413C29E2A98D2 CRC64; MDSLLKKQRQ FLYQFKNVRW AKGRHETYLC YVVKRRDSPT SFSLDFGHLR NKAGCHVELL FLRYISDWDL DPGRCYRVTW FTSWSPCYDC ARHVADFLRG YPNLSLRIFT ARLYFCDKER KAEPEGLRRL HRAGVQIAIM TFKDYFYCWN TFVENHERTF KAWEGLHENS VRLSRQLRRI LLPLYEVDDL RDAFRTLGL //