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Q9GZX7 (AICDA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Single-stranded DNA cytosine deaminase

EC=3.5.4.38
Alternative name(s):
Activation-induced cytidine deaminase
Cytidine aminohydrolase
Gene names
Name:AICDA
Synonyms:AID
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length198 AA.
Sequence statusComplete.
Protein existenceEvidence 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.10 Ref.11 Ref.12 Ref.14

Catalytic activity

Cytosine in single-stranded DNA + H2O = uracil in single-stranded DNA + 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. Interacts with TRIM28 and NCL By similarity. Interacts with SUPT6H. Ref.9 Ref.10 Ref.12 Ref.14

Subcellular location

Nucleus. Cytoplasm. Note: Predominantly cytoplasmic but shuttles between the nucleus and the cytoplasm. Ref.8 Ref.10 Ref.12 Ref.13 Ref.15

Tissue specificity

Strongly expressed in lymph nodes and tonsils. Ref.15

Induction

Negatively regulated by microRNA-155 (miR-155). Ref.15

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2

Sequence similarities

Belongs to the cytidine and deoxycytidylate deaminase family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9GZX7-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9GZX7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     143-152: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 198198Single-stranded DNA cytosine deaminase
PRO_0000171687

Regions

Region1 – 3030Nuclear localization signal
Region2 – 2625Interaction with SUPT6H
Region39 – 424Important for interaction with CTNNBL1
Region183 – 19816Nuclear export signal

Sites

Active site581Proton donor By similarity
Metal binding561Zinc; catalytic By similarity
Metal binding871Zinc; catalytic By similarity
Metal binding901Zinc; catalytic By similarity

Amino acid modifications

Modified residue271Phosphothreonine; by PKA Ref.9
Modified residue381Phosphoserine; by PKA Ref.9 Ref.10

Natural variations

Alternative sequence143 – 15210Missing in isoform 2.
VSP_047803
Natural variant241R → W in HIGM2; Completely abolishes nuclear import and interaction with CTNNBL1, diminishes interaction with KPNA1 and abolishes immunoglobulin class switching. Ref.2 Ref.12
VAR_013774
Natural variant251R → C. Ref.16
VAR_014091
Natural variant801W → R in HIGM2. Ref.2
VAR_013775
Natural variant1061L → P in HIGM2. Ref.2
VAR_013776
Natural variant1391M → V in HIGM2. Ref.2
VAR_013777
Natural variant1511F → S in HIGM2. Ref.2
VAR_013778

Experimental info

Mutagenesis101K → A: Little effect on nuclear import; when associated with A-193. No effect on CTNNBL1 binding. Ref.12
Mutagenesis181V → 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.12
Mutagenesis191R → 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.12
Mutagenesis201W → K: Impaired nuclear import; when associated with A-193. No effect on CTNNBL1 binding. Ref.12
Mutagenesis271T → A: Loss of phosphorylation. No effect on cytidine deaminase activity. Impaired class-switch recombination activity. Ref.9 Ref.13
Mutagenesis271T → E: Phosphomimetic mutant which shows loss of cytidine deaminase activity and impaired class-switch recombination activity. Ref.9 Ref.13
Mutagenesis381S → A: Loss of phosphorylation. Impaired class-switch recombination activity. No effect on interaction with CTNNBL1. Ref.9 Ref.10
Mutagenesis381S → D: No effect on interaction with CTNNBL1. Ref.9 Ref.10
Mutagenesis39 – 424ATSF → 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.10
Mutagenesis501R → G: Some reduced nuclear import; when associated with A-193. Ref.12
Mutagenesis1121R → D: Greatly reduced nuclear import; when associated with A-193. Ref.12
Mutagenesis1931F → 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.12
Sequence conflict1191R → H in AAM95406. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 3C27BB143DB184A9

FASTA19823,954
        10         20         30         40         50         60 
MDSLLMNRRK FLYQFKNVRW AKGRRETYLC YVVKRRDSAT SFSLDFGYLR NKNGCHVELL 

        70         80         90        100        110        120 
FLRYISDWDL DPGRCYRVTW FTSWSPCYDC ARHVADFLRG NPNLSLRIFT ARLYFCEDRK 

       130        140        150        160        170        180 
AEPEGLRRLH RAGVQIAIMT FKDYFYCWNT FVENHERTFK AWEGLHENSV RLSRQLRRIL 

       190 
LPLYEVDDLR DAFRTLGL 

« Hide

Isoform 2 [UniParc].

Checksum: 02C20DFDA47793E3
Show »

FASTA18822,614

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] (ISOFORM 1).
[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. expand/collapse author list , Honjo T., Fischer A., Durandy A.
Cell 102:565-575(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANTS HIGM2 TRP-24; ARG-80; PRO-106; VAL-139 AND SER-151.
[3]"Somatic hypermutation of the AID transgene in B and non-B cells."
Martin A., Scharff M.D.
Proc. Natl. Acad. Sci. U.S.A. 99:12304-12308(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Intracellular localization of AID isoforms."
Roa S., Gonzalez-Sarmiento R.
Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]"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] (ISOFORM 1).
[6]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] (ISOFORM 1).
Tissue: B-cell.
[8]"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.
[9]"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.
[10]"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, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF 39-ALA--PHE-42 AND SER-38.
[11]"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.
[12]"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.
[13]"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.
[14]"Histone chaperone Spt6 is required for class switch recombination but not somatic hypermutation."
Okazaki I.M., Okawa K., Kobayashi M., Yoshikawa K., Kawamoto S., Nagaoka H., Shinkura R., Kitawaki Y., Taniguchi H., Natsume T., Iemura S., Honjo T.
Proc. Natl. Acad. Sci. U.S.A. 108:7920-7925(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SUPT6H.
[15]"BCL6 positively regulates AID and germinal center gene expression via repression of miR-155."
Basso K., Schneider C., Shen Q., Holmes A.B., Setty M., Leslie C., Dalla-Favera R.
J. Exp. Med. 209:2455-2465(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[16]"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.
AF529819 mRNA. Translation: AAM95406.1.
AY536516 mRNA. Translation: AAS92920.1.
BT007402 mRNA. Translation: AAP36066.1.
AC092184 Genomic DNA. No translation available.
BC006296 mRNA. Translation: AAH06296.1.
RefSeqNP_065712.1. NM_020661.2.
UniGeneHs.149342.

3D structure databases

ProteinModelPortalQ9GZX7.
SMRQ9GZX7. Positions 6-180.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121497. 55 interactions.
DIPDIP-48519N.
IntActQ9GZX7. 23 interactions.
MINTMINT-4717382.
STRING9606.ENSP00000229335.

PTM databases

PhosphoSiteQ9GZX7.

Polymorphism databases

DMDM23813666.

Proteomic databases

PaxDbQ9GZX7.
PRIDEQ9GZX7.

Protocols and materials databases

DNASU57379.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000229335; ENSP00000229335; ENSG00000111732. [Q9GZX7-1]
ENST00000537228; ENSP00000445691; ENSG00000111732. [Q9GZX7-2]
GeneID57379.
KEGGhsa:57379.
UCSCuc001qur.2. human. [Q9GZX7-1]

Organism-specific databases

CTD57379.
GeneCardsGC12M008754.
HGNCHGNC:13203. AICDA.
MIM605257. gene.
605258. phenotype.
neXtProtNX_Q9GZX7.
Orphanet101089. Hyper-IgM syndrome type 2.
PharmGKBPA24644.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39659.
HOGENOMHOG000033754.
HOVERGENHBG050434.
InParanoidQ9GZX7.
KOK10989.
OMAIMTFKDY.
OrthoDBEOG708W0R.
PhylomeDBQ9GZX7.
TreeFamTF331356.

Gene expression databases

ArrayExpressQ9GZX7.
BgeeQ9GZX7.
CleanExHS_AICDA.
GenevestigatorQ9GZX7.

Family and domain databases

InterProIPR016192. APOBEC/CMP_deaminase_Zn-bd.
IPR013158. APOBEC_N.
IPR016193. Cytidine_deaminase-like.
[Graphical view]
PfamPF08210. APOBEC_N. 1 hit.
[Graphical view]
SUPFAMSSF53927. SSF53927. 1 hit.
PROSITEPS00903. CYT_DCMP_DEAMINASES. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiAICDA.
GenomeRNAi57379.
NextBio63478.
PROQ9GZX7.
SOURCESearch...

Entry information

Entry nameAICDA_HUMAN
AccessionPrimary (citable) accession number: Q9GZX7
Secondary accession number(s): Q6QJ81, Q8NFC1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 10, 2002
Last sequence update: March 1, 2001
Last modified: April 16, 2014
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM