AICDA_CANLF
ID AICDA_CANLF Reviewed; 198 AA.
AC Q75W64;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=Single-stranded DNA cytosine deaminase;
DE EC=3.5.4.38 {ECO:0000250|UniProtKB:Q9GZX7};
DE AltName: Full=Activation-induced cytidine deaminase;
DE Short=AID;
DE AltName: Full=Cytidine aminohydrolase;
GN Name=AICDA; Synonyms=AID;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Lymph node;
RX PubMed=15240955; DOI=10.1292/jvms.66.739;
RA Ohmori K., Maeda S., Okayama T., Masuda K., Ohno K., Tsujimoto H.;
RT "Molecular cloning of canine activation-induced cytidine deaminase (AID)
RT cDNA and its expression in normal tissues.";
RL J. Vet. Med. Sci. 66:739-741(2004).
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:Q9GZX7};
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 thymus, lung, spleen, kidney, small
CC intestine, lymph node and tonsil. {ECO:0000269|PubMed:15240955}.
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; AB122019; BAD15112.1; -; mRNA.
DR RefSeq; NP_001003380.1; NM_001003380.1.
DR AlphaFoldDB; Q75W64; -.
DR SMR; Q75W64; -.
DR STRING; 9615.ENSCAFP00000056099; -.
DR PaxDb; Q75W64; -.
DR GeneID; 442983; -.
DR KEGG; cfa:442983; -.
DR CTD; 57379; -.
DR eggNOG; KOG4075; Eukaryota.
DR InParanoid; Q75W64; -.
DR OrthoDB; 1237707at2759; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0004126; F:cytidine deaminase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0009972; P:cytidine deamination; ISS:UniProtKB.
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 assembly; ISS:UniProtKB.
DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; ISS: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 2: Evidence at transcript 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_0000171686"
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"
SQ SEQUENCE 198 AA; 23887 MW; 4BE00D9B9D1550D2 CRC64;
MDSLLMKQRK FLYHFKNVRW AKGRHETYLC YVVKRRDSAT SFSLDFGHLR NKSGCHVELL
FLRYISDWDL DPGRCYRVTW FTSWSPCYDC ARHVADFLRG YPNLSLRIFA ARLYFCEDRK
AEPEGLRRLH RAGVQIAIMT FKDYFYCWNT FVENREKTFK AWEGLHENSV RLSRQLRRIL
LPLYEVDDLR DAFRTLGL
