ID AICDA_HUMAN Reviewed; 198 AA. AC Q9GZX7; DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 25-JAN-2012, entry version 96. DE RecName: Full=Activation-induced cytidine deaminase; DE EC=3.5.4.5; DE AltName: Full=Cytidine aminohydrolase; GN Name=AICDA; Synonyms=AID; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RX MEDLINE=20408890; PubMed=10950930; DOI=10.1006/geno.2000.6268; RA Muto T., Muramatsu M., Taniwaki M., Kinoshita K., Honjo T.; RT "Isolation, tissue distribution, and chromosomal localization of the RT human activation-induced cytidine deaminase (hAID) gene."; RL Genomics 68:85-88(2000). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANTS HIGM2 TRP-24; RP ARG-80; PRO-106; VAL-139 AND SER-151. RX MEDLINE=20460541; PubMed=11007475; DOI=10.1016/S0092-8674(00)00079-9; RA Revy P., Muto T., Levy Y., Geissmann F., Plebani A., Sanal O., RA Catalan N., Forveille M., Dufourcq-Lagelouse R., Gennery A., RA Tezcan I., Ersoy F., Kayserili H., Ugazio A.G., Brousse N., RA Muramatsu M., Notarangelo L.D., Kinoshita K., Honjo T., Fischer A., RA Durandy A.; RT "Activation-induced cytidine deaminase (AID) deficiency causes the RT autosomal recessive form of the Hyper-IgM syndrome (HIGM2)."; RL Cell 102:565-575(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=B-cell; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION IN DNA DEMETHYLATION. RX PubMed=21496894; DOI=10.1016/j.cell.2011.03.022; RA Guo J.U., Su Y., Zhong C., Ming G.L., Song H.; RT "Hydroxylation of 5-methylcytosine by TET1 promotes active DNA RT demethylation in the adult brain."; RL Cell 145:423-434(2011). RN [6] RP VARIANT CYS-25. RX MEDLINE=21429198; PubMed=11544457; DOI=10.1067/mai.2001.117456; RA Noguchi E., Shibasaki M., Inudou M., Kamioka M., Yokouchi Y., RA Yamakawa-Kobayashi K., Hamaguchi H., Matsui A., Arinami T.; RT "Association between a new polymorphism in the activation-induced RT cytidine deaminase gene and atopic asthma and the regulation of total RT serum IgE levels."; RL J. Allergy Clin. Immunol. 108:382-386(2001). CC -!- FUNCTION: Single-stranded DNA-specific cytidine deaminase. CC Involved in somatic hypermutation, gene conversion, and class- CC switch recombination in B-lymphocytes. Required for several CC crucial steps of B-cell terminal differentiation necessary for CC efficient antibody responses. May also play a role in the CC epigenetic regulation of gene expression by participating in DNA CC demethylation. CC -!- CATALYTIC ACTIVITY: Cytidine + H(2)O = uridine + NH(3). CC -!- COFACTOR: Zinc (By similarity). CC -!- INTERACTION: CC P24522:GADD45A; NbExp=5; IntAct=EBI-3834328, EBI-448167; CC Q13569:TDG; NbExp=5; IntAct=EBI-3834328, EBI-348333; CC -!- TISSUE SPECIFICITY: Strongly expressed in lymph nodes and tonsils. CC -!- DISEASE: Defects in AICDA are the cause of immunodeficiency with CC hyper-IgM type 2 (HIGM2) [MIM:605258]. A rare immunodeficiency CC syndrome characterized by normal or elevated serum IgM levels with CC absence of IgG, IgA, and IgE. It results in a profound CC susceptibility to bacterial infections. CC -!- SIMILARITY: Belongs to the cytidine and deoxycytidylate deaminase CC family. CC -!- WEB RESOURCE: Name=AICDAbase; Note=AICDA mutation db; CC URL="http://bioinf.uta.fi/AICDAbase/"; CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/AICDA"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AB040431; BAB12721.1; -; mRNA. DR EMBL; AB040430; BAB12720.1; -; Genomic_DNA. DR EMBL; BT007402; AAP36066.1; -; mRNA. DR EMBL; BC006296; AAH06296.1; -; mRNA. DR IPI; IPI00010186; -. DR RefSeq; NP_065712.1; NM_020661.2. DR UniGene; Hs.149342; -. DR ProteinModelPortal; Q9GZX7; -. DR SMR; Q9GZX7; 3-182. DR DIP; DIP-48519N; -. DR IntAct; Q9GZX7; 10. DR STRING; Q9GZX7; -. DR PhosphoSite; Q9GZX7; -. DR DMDM; 23813666; -. DR PRIDE; Q9GZX7; -. DR Ensembl; ENST00000229335; ENSP00000229335; ENSG00000111732. DR GeneID; 57379; -. DR KEGG; hsa:57379; -. DR UCSC; uc001qur.1; human. DR CTD; 57379; -. DR GeneCards; GC12M008754; -. DR H-InvDB; HIX0010409; -. DR HGNC; HGNC:13203; AICDA. DR MIM; 605257; gene. DR MIM; 605258; phenotype. DR neXtProt; NX_Q9GZX7; -. DR Orphanet; 101089; Hyper-IgM syndrome type 2. DR GeneTree; ENSGT00530000062933; -. DR HOGENOM; HBG716052; -. DR HOVERGEN; HBG050434; -. DR InParanoid; Q9GZX7; -. DR OMA; CWNTFVE; -. DR OrthoDB; EOG4GQQ5W; -. DR Pathway_Interaction_DB; il4_2pathway; IL4-mediated signaling events. DR NextBio; 63478; -. DR ArrayExpress; Q9GZX7; -. DR Bgee; Q9GZX7; -. DR CleanEx; HS_AICDA; -. DR Genevestigator; Q9GZX7; -. DR GermOnline; ENSG00000111732; Homo sapiens. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0004126; F:cytidine deaminase activity; IDA:UniProtKB. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0030183; P:B cell differentiation; NAS:UniProtKB. DR GO; GO:0080111; P:DNA demethylation; IDA:UniProtKB. DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW. DR GO; GO:0090310; P:negative regulation of methylation-dependent chromatin silencing; IDA:UniProtKB. DR InterPro; IPR016192; APOBEC/CMP_deaminase_Zn-bd. DR InterPro; IPR007904; APOBEC_C. DR InterPro; IPR013158; APOBEC_N. DR InterPro; IPR016193; Cytidine_deaminase-like. DR KO; K10989; -. DR Pfam; PF05240; APOBEC_C; 1. DR Pfam; PF08210; APOBEC_N; 1. DR SUPFAM; SSF53927; Cytidine_deaminase-like; 1. DR PROSITE; PS00903; CYT_DCMP_DEAMINASES; 1. PE 1: Evidence at protein level; KW Complete proteome; Disease mutation; Hydrolase; Metal-binding; KW mRNA processing; Polymorphism; Reference proteome; Zinc. FT CHAIN 1 198 Activation-induced cytidine deaminase. FT /FTId=PRO_0000171687. FT ACT_SITE 58 58 Proton donor (By similarity). FT METAL 56 56 Zinc; catalytic (By similarity). FT METAL 87 87 Zinc; catalytic (By similarity). FT METAL 90 90 Zinc; catalytic (By similarity). FT VARIANT 24 24 R -> W (in HIGM2). FT /FTId=VAR_013774. FT VARIANT 25 25 R -> C. FT /FTId=VAR_014091. FT VARIANT 80 80 W -> R (in HIGM2). FT /FTId=VAR_013775. FT VARIANT 106 106 L -> P (in HIGM2). FT /FTId=VAR_013776. FT VARIANT 139 139 M -> V (in HIGM2). FT /FTId=VAR_013777. FT VARIANT 151 151 F -> S (in HIGM2). FT /FTId=VAR_013778. SQ SEQUENCE 198 AA; 23954 MW; 3C27BB143DB184A9 CRC64; MDSLLMNRRK FLYQFKNVRW AKGRRETYLC YVVKRRDSAT SFSLDFGYLR NKNGCHVELL FLRYISDWDL DPGRCYRVTW FTSWSPCYDC ARHVADFLRG NPNLSLRIFT ARLYFCEDRK AEPEGLRRLH RAGVQIAIMT FKDYFYCWNT FVENHERTFK AWEGLHENSV RLSRQLRRIL LPLYEVDDLR DAFRTLGL //