Q9GZX7 (AICDA_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 29, 2013.
Version 111.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Activation-induced cytidine deaminase EC=3.5.4.5 Alternative name(s): Cytidine aminohydrolase | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 198 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Single-stranded DNA-specific cytidine deaminase. Involved in somatic hypermutation, gene conversion, and class-switch recombination in B-lymphocytes. Required for several crucial steps of B-cell terminal differentiation necessary for efficient antibody responses. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Ref.7 Ref.8 Ref.9 |
| Catalytic activity | Cytidine + H2O = uridine + NH3. |
| Cofactor | Zinc By similarity. |
| Subunit structure | Interacts with CTNNBL1; the interaction is important for the immunoglobulin switch activity of AICDA. Interacts (via its NLS) with KPNA1. Interacts with PKA/PRKACA and PRKAR1A/PKR1. Ref.6 Ref.7 Ref.9 |
| Subcellular location | Nucleus. Cytoplasm. Note: Predominantly cytoplasmic but shuttles between the nucleus and the cytoplasm. Ref.5 Ref.7 Ref.9 Ref.10 |
| Tissue specificity | Strongly expressed in lymph nodes and tonsils. |
| Post-translational modification | Ser-38 is the major site whereas Thr-27 is the minor site of phosphorylation. Phosphorylation regulates its class-switch recombination activity. |
| Involvement in disease | Immunodeficiency with hyper-IgM 2 (HIGM2) [MIM:605258]: A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections. |
| Sequence similarities | Belongs to the cytidine and deoxycytidylate deaminase family. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| GADD45A | P24522 | 5 | EBI-3834328,EBI-448167 | |
| TDG | Q13569 | 5 | EBI-3834328,EBI-348333 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 198 | 198 | Activation-induced cytidine deaminase | PRO_0000171687 | |||||
Regions | |||||||||
| Region | 1 – 30 | 30 | Nuclear localization signal | ||||||
| Region | 39 – 42 | 4 | Important for interaction with CTNNBL1 | ||||||
| Region | 183 – 198 | 16 | Nuclear export signal | ||||||
Sites | |||||||||
| Active site | 58 | 1 | Proton donor By similarity | ||||||
| Metal binding | 56 | 1 | Zinc; catalytic By similarity | ||||||
| Metal binding | 87 | 1 | Zinc; catalytic By similarity | ||||||
| Metal binding | 90 | 1 | Zinc; catalytic By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 27 | 1 | Phosphothreonine; by PKA Ref.6 | ||||||
| Modified residue | 38 | 1 | Phosphoserine; by PKA Ref.6 Ref.7 | ||||||
Natural variations | |||||||||
| Natural variant | 24 | 1 | R → W in HIGM2; Completely abolishes nuclear import and interaction with CTNNBL1, diminishes interaction with KPNA1 and abolishes immunoglobulin class switching. Ref.2 Ref.9 | VAR_013774 | |||||
| Natural variant | 25 | 1 | R → C. Ref.11 | VAR_014091 | |||||
| Natural variant | 80 | 1 | W → R in HIGM2. Ref.2 | VAR_013775 | |||||
| Natural variant | 106 | 1 | L → P in HIGM2. Ref.2 | VAR_013776 | |||||
| Natural variant | 139 | 1 | M → V in HIGM2. Ref.2 | VAR_013777 | |||||
| Natural variant | 151 | 1 | F → S in HIGM2. Ref.2 | VAR_013778 | |||||
Experimental info | |||||||||
| Mutagenesis | 10 | 1 | K → A: Little effect on nuclear import; when associated with A-193. No effect on CTNNBL1 binding. Ref.9 | ||||||
| Mutagenesis | 18 | 1 | V → S: Greatly impaired nuclear import; when associated with V-19 and A-193. Reduced interaction with both CTNNBL1 and KPNA1, and abolishes immunoglobulin class switching; when associated with V-19. Ref.9 | ||||||
| Mutagenesis | 19 | 1 | R → V: Greatly impaired nuclear import; when associated with S-18 and A-193. Reduced interaction with both CTNNBL1 and KPNA1, and abolishes immunoglobulin class switching; when associated with S-18. Ref.9 | ||||||
| Mutagenesis | 20 | 1 | W → K: Impaired nuclear import; when associated with A-193. No effect on CTNNBL1 binding. Ref.9 | ||||||
| Mutagenesis | 27 | 1 | T → A: Loss of phosphorylation. No effect on cytidine deaminase activity. Impaired class-switch recombination activity. Ref.6 Ref.10 | ||||||
| Mutagenesis | 27 | 1 | T → E: Phosphomimetic mutant which shows loss of cytidine deaminase activity and impaired class-switch recombination activity. Ref.6 Ref.10 | ||||||
| Mutagenesis | 38 | 1 | S → A: Loss of phosphorylation. Impaired class-switch recombination activity. No effect on interaction with CTNNBL1. Ref.6 Ref.7 | ||||||
| Mutagenesis | 38 | 1 | S → D: No effect on interaction with CTNNBL1. Ref.6 Ref.7 | ||||||
| Mutagenesis | 39 – 42 | 4 | ATSF → GGQV: Greatly reduced interaction with CTNNBL1 but no effect on subcellular location, enzyme activity, ability to oligomerize nor on phosphorylation at Ser-38. Diminished antibody diversification. Ref.7 | ||||||
| Mutagenesis | 50 | 1 | R → G: Some reduced nuclear import; when associated with A-193. Ref.9 | ||||||
| Mutagenesis | 112 | 1 | R → D: Greatly reduced nuclear import; when associated with A-193. Ref.9 | ||||||
| Mutagenesis | 193 | 1 | F → A: Completely abolishes nuclear import; when associated with W-24 or D-112. Little affect on nuclear import; when associated with A-10. Greatly impaired nuclear import; when associated with K-20 or G-50. Almost completely abolishes nuclear import; when associated with S-18 and V-19. Ref.9 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Isolation, tissue distribution, and chromosomal localization of the human activation-induced cytidine deaminase (hAID) gene." Muto T., Muramatsu M., Taniwaki M., Kinoshita K., Honjo T. Genomics 68:85-88(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. |
| [2] | "Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2)." Revy P., Muto T., Levy Y., Geissmann F., Plebani A., Sanal O., Catalan N., Forveille M., Dufourcq-Lagelouse R., Gennery A., Tezcan I., Ersoy F., Kayserili H., Ugazio A.G., Brousse N., Muramatsu M., Notarangelo L.D., Kinoshita K. Durandy A.Cell 102:565-575(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANTS HIGM2 TRP-24; ARG-80; PRO-106; VAL-139 AND SER-151. |
| [3] | "Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [4] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: B-cell. |
| [5] | "Activation-induced cytidine deaminase shuttles between nucleus and cytoplasm like apolipoprotein B mRNA editing catalytic polypeptide 1." Ito S., Nagaoka H., Shinkura R., Begum N., Muramatsu M., Nakata M., Honjo T. Proc. Natl. Acad. Sci. U.S.A. 101:1975-1980(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION. |
| [6] | "PKA-mediated phosphorylation regulates the function of activation-induced deaminase (AID) in B cells." Pasqualucci L., Kitaura Y., Gu H., Dalla-Favera R. Proc. Natl. Acad. Sci. U.S.A. 103:395-400(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-27 AND SER-38, INTERACTION WITH PRKACA AND PRKAR1A, MUTAGENESIS OF THR-27 AND SER-38. |
| [7] | "Interaction between antibody-diversification enzyme AID and spliceosome-associated factor CTNNBL1." Conticello S.G., Ganesh K., Xue K., Lu M., Rada C., Neuberger M.S. Mol. Cell 31:474-484(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CTNNBL1, FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-38, MASS SPECTROMETRY, MUTAGENESIS OF 39-ALA--PHE-42 AND SER-38. |
| [8] | "Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain." Guo J.U., Su Y., Zhong C., Ming G.L., Song H. Cell 145:423-434(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DNA DEMETHYLATION. |
| [9] | "CTNNBL1 is a novel nuclear localization sequence-binding protein that recognizes RNA-splicing factors CDC5L and Prp31." Ganesh K., Adam S., Taylor B., Simpson P., Rada C., Neuberger M. J. Biol. Chem. 286:17091-17102(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CTNNBL1, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-10; VAL-18; ARG-19; TRP-20; ARG-50; ARG-112 AND PHE-193, CHARACTERIZATION OF VARIANT TRP-24. |
| [10] | "Phosphorylation directly regulates the intrinsic DNA cytidine deaminase activity of activation-induced deaminase and APOBEC3G protein." Demorest Z.L., Li M., Harris R.S. J. Biol. Chem. 286:26568-26575(2011) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF THR-27. |
| [11] | "Association between a new polymorphism in the activation-induced cytidine deaminase gene and atopic asthma and the regulation of total serum IgE levels." Noguchi E., Shibasaki M., Inudou M., Kamioka M., Yokouchi Y., Yamakawa-Kobayashi K., Hamaguchi H., Matsui A., Arinami T. J. Allergy Clin. Immunol. 108:382-386(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CYS-25. |
| + | Additional computationally mapped references. |
Web resources
| AICDAbase AICDA mutation db |
| GeneReviews |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AB040431 mRNA. Translation: BAB12721.1. AB040430 Genomic DNA. Translation: BAB12720.1. BT007402 mRNA. Translation: AAP36066.1. BC006296 mRNA. Translation: AAH06296.1. |
| IPI | IPI00010186. |
| RefSeq | NP_065712.1. NM_020661.2. |
| UniGene | Hs.149342. |
3D structure databases | |
| ProteinModelPortal | Q9GZX7. |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP-48519N. |
| IntAct | Q9GZX7. 10 interactions. |
| MINT | MINT-4717382. |
| STRING | 9606.ENSP00000229335. |
PTM databases | |
| PhosphoSite | Q9GZX7. |
Polymorphism databases | |
| DMDM | 23813666. |
Proteomic databases | |
| PaxDb | Q9GZX7. |
| PRIDE | Q9GZX7. |
Protocols and materials databases | |
| DNASU | 57379. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000229335; ENSP00000229335; ENSG00000111732. |
| GeneID | 57379. |
| KEGG | hsa:57379. |
| UCSC | uc001qur.2. human. |
Organism-specific databases | |
| CTD | 57379. |
| GeneCards | GC12M008754. |
| HGNC | HGNC:13203. AICDA. |
| MIM | 605257. gene. 605258. phenotype. |
| neXtProt | NX_Q9GZX7. |
| Orphanet | 101089. Hyper-IgM syndrome type 2. |
| PharmGKB | PA24644. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | NOG39659. |
| HOGENOM | HOG000033754. |
| HOVERGEN | HBG050434. |
| InParanoid | Q9GZX7. |
| KO | K10989. |
| OMA | IMTFKDY. |
| OrthoDB | EOG4GQQ5W. |
Enzyme and pathway databases | |
| Pathway_Interaction_DB | il4_2pathway. IL4-mediated signaling events. |
Gene expression databases | |
| ArrayExpress | Q9GZX7. |
| Bgee | Q9GZX7. |
| CleanEx | HS_AICDA. |
| Genevestigator | Q9GZX7. |
| GermOnline | ENSG00000111732. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR016192. APOBEC/CMP_deaminase_Zn-bd. IPR013158. APOBEC_N. IPR016193. Cytidine_deaminase-like. [Graphical view] |
| Pfam | PF08210. APOBEC_N. 1 hit. [Graphical view] |
| SUPFAM | SSF53927. Cytidine_deaminase-like. 1 hit. |
| PROSITE | PS00903. CYT_DCMP_DEAMINASES. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| GenomeRNAi | 57379. |
| NextBio | 63478. |
| SOURCE | Search... |
Entry information
| Entry name | AICDA_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9GZX7 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 12 Human chromosome 12: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
