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}.
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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
//
