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AICDA_MOUSE
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   03-AUG-2022, entry version 146.
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}.
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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; Q9WVE0; -.
DR   PRIDE; Q9WVE0; -.
DR   Antibodypedia; 6178; 440 antibodies from 43 providers.
DR   DNASU; 11628; -.
DR   Ensembl; ENSMUST00000043301; ENSMUSP00000040524; ENSMUSG00000040627.
DR   GeneID; 11628; -.
DR   KEGG; mmu:11628; -.
DR   UCSC; uc009dpj.1; mouse.
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; AARLYFC; -.
DR   OrthoDB; 1237707at2759; -.
DR   PhylomeDB; Q9WVE0; -.
DR   TreeFam; TF331356; -.
DR   BRENDA; 3.5.4.38; 3474.
DR   BioGRID-ORCS; 11628; 1 hit in 109 CRISPR screens.
DR   PRO; PR:Q9WVE0; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   RNAct; Q9WVE0; protein.
DR   Bgee; ENSMUSG00000040627; Expressed in cumulus cell and 38 other tissues.
DR   ExpressionAtlas; Q9WVE0; baseline and differential.
DR   Genevisible; Q9WVE0; MM.
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: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 assembly; 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:0010529; P:negative regulation of transposition; 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   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   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
 
 
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