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Protein

Single-stranded DNA cytosine deaminase

Gene

AICDA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Single-stranded DNA-specific cytidine deaminase. Involved in somatic hypermutation (SHM), gene conversion, and class-switch recombination (CSR) in B-lymphocytes by deaminating C to U during transcription of Ig-variable (V) and Ig-switch (S) region DNA. Required for several crucial steps of B-cell terminal differentiation necessary for efficient antibody responses (PubMed:18722174, PubMed:21385873, PubMed:21518874, PubMed:27716525). May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation (PubMed:21496894).5 Publications

Catalytic activityi

Cytosine in single-stranded DNA + H2O = uracil in single-stranded DNA + NH3.1 Publication

Cofactori

Zn2+1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi56Zinc; catalytic1 Publication1
Active sitei58Proton donorBy similarity1
Metal bindingi87Zinc; catalytic1 Publication1
Metal bindingi90Zinc; catalytic1 Publication1

GO - Molecular functioni

  • cytidine deaminase activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • B cell differentiation Source: UniProtKB
  • cellular response to lipopolysaccharide Source: Ensembl
  • defense response to bacterium Source: Ensembl
  • DNA demethylation Source: UniProtKB
  • isotype switching Source: Ensembl
  • mRNA processing Source: UniProtKB-KW
  • negative regulation of methylation-dependent chromatin silencing Source: UniProtKB
  • somatic diversification of immunoglobulins Source: UniProtKB
  • somatic hypermutation of immunoglobulin genes Source: UniProtKB

Keywordsi

Molecular functionHydrolase
Biological processmRNA processing
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.5.4.38. 2681.
SIGNORiQ9GZX7.

Names & Taxonomyi

Protein namesi
Recommended name:
Single-stranded DNA cytosine deaminase (EC:3.5.4.381 Publication)
Alternative name(s):
Activation-induced cytidine deaminase
Short name:
AID
Cytidine aminohydrolase
Gene namesi
Name:AICDA
Synonyms:AID
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:13203. AICDA.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: UniProtKB

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency with hyper-IgM 2 (HIGM2)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:605258
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07756315F → L in HIGM2. 1 Publication1
Natural variantiVAR_01377424R → W in HIGM2; completely abolishes nuclear import and interaction with CTNNBL1, diminishes interaction with KPNA1 and abolishes immunoglobulin class switching. 3 PublicationsCorresponds to variant dbSNP:rs104894324Ensembl.1
Natural variantiVAR_07756431Y → H in HIGM2. 1 Publication1
Natural variantiVAR_07756556H → Y in HIGM2; unknown pathological significance; loss of mutagenic activity. 2 Publications1
Natural variantiVAR_01377580W → R in HIGM2. 2 PublicationsCorresponds to variant dbSNP:rs104894320Ensembl.1
Natural variantiVAR_07756687C → R in HIGM2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs762590894Ensembl.1
Natural variantiVAR_013776106L → P in HIGM2. 2 PublicationsCorresponds to variant dbSNP:rs104894321Ensembl.1
Natural variantiVAR_077567130H → P in HIGM2; slightly decreased mutagenic activity. 2 Publications1
Natural variantiVAR_013777139M → V in HIGM2. 2 PublicationsCorresponds to variant dbSNP:rs104894322Ensembl.1
Natural variantiVAR_013778151F → S in HIGM2. 2 PublicationsCorresponds to variant dbSNP:rs104894327Ensembl.1
Natural variantiVAR_077568174R → S in HIGM2; unknown pathological significance. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi10K → A: Little effect on nuclear import; when associated with A-193. No effect on CTNNBL1 binding. 1 Publication1
Mutagenesisi18V → 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. 1 Publication1
Mutagenesisi19R → 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. 1 Publication1
Mutagenesisi20W → K: Impaired nuclear import; when associated with A-193. No effect on CTNNBL1 binding. 1 Publication1
Mutagenesisi27T → A: Loss of phosphorylation. No effect on cytidine deaminase activity. Impaired class-switch recombination activity. 2 Publications1
Mutagenesisi27T → E: Phosphomimetic mutant which shows loss of cytidine deaminase activity and impaired class-switch recombination activity. 2 Publications1
Mutagenesisi38S → A: Loss of phosphorylation. Impaired class-switch recombination activity. No effect on interaction with CTNNBL1. 2 Publications1
Mutagenesisi38S → D: No effect on interaction with CTNNBL1. 2 Publications1
Mutagenesisi39 – 42ATSF → 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. 1 Publication4
Mutagenesisi50R → G: Some reduced nuclear import; when associated with A-193. 1 Publication1
Mutagenesisi112R → D: Greatly reduced nuclear import; when associated with A-193. 1 Publication1
Mutagenesisi193F → 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. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi57379.
MalaCardsiAICDA.
MIMi605258. phenotype.
OpenTargetsiENSG00000111732.
Orphaneti101089. Hyper-IgM syndrome type 2.
PharmGKBiPA24644.

Polymorphism and mutation databases

BioMutaiAICDA.
DMDMi23813666.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001716871 – 198Single-stranded DNA cytosine deaminaseAdd BLAST198

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei27Phosphothreonine; by PKA1 Publication1
Modified residuei38Phosphoserine; by PKA2 Publications1

Post-translational modificationi

Ser-38 is the major site whereas Thr-27 is the minor site of phosphorylation. Phosphorylation regulates its class-switch recombination activity.2 Publications
Probably monoubiquitinated on several residues by RNF126.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9GZX7.
PaxDbiQ9GZX7.
PeptideAtlasiQ9GZX7.
PRIDEiQ9GZX7.

PTM databases

iPTMnetiQ9GZX7.
PhosphoSitePlusiQ9GZX7.

Expressioni

Tissue specificityi

Strongly expressed in lymph nodes and tonsils.1 Publication

Inductioni

Negatively regulated by microRNA-155 (miR-155).1 Publication

Gene expression databases

BgeeiENSG00000111732.
CleanExiHS_AICDA.
ExpressionAtlasiQ9GZX7. baseline and differential.
GenevisibleiQ9GZX7. HS.

Interactioni

Subunit structurei

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. Interacts with RNF126.By similarity5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi121497. 54 interactors.
DIPiDIP-48519N.
IntActiQ9GZX7. 24 interactors.
MINTiMINT-4717382.
STRINGi9606.ENSP00000229335.

Structurei

Secondary structure

1198
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi28 – 36Combined sources9
Beta strandi42 – 50Combined sources9
Helixi57 – 68Combined sources12
Beta strandi74 – 84Combined sources11
Helixi88 – 99Combined sources12
Beta strandi104 – 112Combined sources9
Helixi122 – 131Combined sources10
Beta strandi135 – 138Combined sources4
Helixi141 – 150Combined sources10
Helixi165 – 179Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5JJ4X-ray2.81A/B/C23-183[»]
ProteinModelPortaliQ9GZX7.
SMRiQ9GZX7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini23 – 129CMP/dCMP-type deaminasePROSITE-ProRule annotationAdd BLAST107

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 26Interaction with SUPT6H1 PublicationAdd BLAST25
Regioni39 – 42Important for interaction with CTNNBL11 Publication4
Regioni88 – 116Required for interaction with RNF1261 PublicationAdd BLAST29

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1 – 30Bipartite nuclear localization signal1 PublicationAdd BLAST30
Motifi183 – 198Nuclear export signal1 PublicationAdd BLAST16

Sequence similaritiesi

Phylogenomic databases

eggNOGiENOG410IFHW. Eukaryota.
ENOG4111HYQ. LUCA.
GeneTreeiENSGT00530000062933.
HOGENOMiHOG000033754.
HOVERGENiHBG050434.
InParanoidiQ9GZX7.
KOiK10989.
OMAiRNKNGCH.
OrthoDBiEOG091G0J2L.
PhylomeDBiQ9GZX7.
TreeFamiTF331356.

Family and domain databases

InterProiView protein in InterPro
IPR016192. APOBEC/CMP_deaminase_Zn-bd.
IPR013158. APOBEC_N.
IPR002125. CMP_dCMP_dom.
IPR016193. Cytidine_deaminase-like.
PfamiView protein in Pfam
PF08210. APOBEC_N. 1 hit.
SUPFAMiSSF53927. SSF53927. 1 hit.
PROSITEiView protein in PROSITE
PS00903. CYT_DCMP_DEAMINASES_1. 1 hit.
PS51747. CYT_DCMP_DEAMINASES_2. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9GZX7-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDSLLMNRRK FLYQFKNVRW AKGRRETYLC YVVKRRDSAT SFSLDFGYLR
60 70 80 90 100
NKNGCHVELL FLRYISDWDL DPGRCYRVTW FTSWSPCYDC ARHVADFLRG
110 120 130 140 150
NPNLSLRIFT ARLYFCEDRK AEPEGLRRLH RAGVQIAIMT FKDYFYCWNT
160 170 180 190
FVENHERTFK AWEGLHENSV RLSRQLRRIL LPLYEVDDLR DAFRTLGL
Length:198
Mass (Da):23,954
Last modified:March 1, 2001 - v1
Checksum:i3C27BB143DB184A9
GO
Isoform 2 (identifier: Q9GZX7-2) [UniParc]FASTAAdd to basket

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

Show »
Length:188
Mass (Da):22,614
Checksum:i02C20DFDA47793E3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti119R → H in AAM95406 (PubMed:12202747).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07756315F → L in HIGM2. 1 Publication1
Natural variantiVAR_01377424R → W in HIGM2; completely abolishes nuclear import and interaction with CTNNBL1, diminishes interaction with KPNA1 and abolishes immunoglobulin class switching. 3 PublicationsCorresponds to variant dbSNP:rs104894324Ensembl.1
Natural variantiVAR_01409125R → C1 Publication1
Natural variantiVAR_07756431Y → H in HIGM2. 1 Publication1
Natural variantiVAR_07756556H → Y in HIGM2; unknown pathological significance; loss of mutagenic activity. 2 Publications1
Natural variantiVAR_01377580W → R in HIGM2. 2 PublicationsCorresponds to variant dbSNP:rs104894320Ensembl.1
Natural variantiVAR_07756687C → R in HIGM2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs762590894Ensembl.1
Natural variantiVAR_013776106L → P in HIGM2. 2 PublicationsCorresponds to variant dbSNP:rs104894321Ensembl.1
Natural variantiVAR_077567130H → P in HIGM2; slightly decreased mutagenic activity. 2 Publications1
Natural variantiVAR_013777139M → V in HIGM2. 2 PublicationsCorresponds to variant dbSNP:rs104894322Ensembl.1
Natural variantiVAR_013778151F → S in HIGM2. 2 PublicationsCorresponds to variant dbSNP:rs104894327Ensembl.1
Natural variantiVAR_077568174R → S in HIGM2; unknown pathological significance. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_047803143 – 152Missing in isoform 2. 1 Publication10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS41747.1. [Q9GZX7-1]
CCDS81662.1. [Q9GZX7-2]
RefSeqiNP_001317272.1. NM_001330343.1. [Q9GZX7-2]
NP_065712.1. NM_020661.3. [Q9GZX7-1]
UniGeneiHs.149342.

Genome annotation databases

EnsembliENST00000229335; ENSP00000229335; ENSG00000111732. [Q9GZX7-1]
ENST00000537228; ENSP00000445691; ENSG00000111732. [Q9GZX7-2]
GeneIDi57379.
KEGGihsa:57379.
UCSCiuc001qur.3. human. [Q9GZX7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiAICDA_HUMAN
AccessioniPrimary (citable) accession number: Q9GZX7
Secondary accession number(s): Q6QJ81, Q8NFC1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 10, 2002
Last sequence update: March 1, 2001
Last modified: June 7, 2017
This is version 147 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families