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Protein

Single-stranded DNA cytosine deaminase

Gene

AICDA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • identical protein binding Source: IntAct
  • RNA binding Source: GO_Central
  • ubiquitin protein ligase binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

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

EuPathDBiHostDB:ENSG00000111732.10
HGNCiHGNC:13203 AICDA
MIMi605257 gene
neXtProtiNX_Q9GZX7

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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:rs104894324EnsemblClinVar.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:rs104894320EnsemblClinVar.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:rs104894321EnsemblClinVar.1
Natural variantiVAR_077567130H → P in HIGM2; slightly decreased mutagenic activity. 2 Publications1
Natural variantiVAR_013777139M → V in HIGM2. 2 PublicationsCorresponds to variant dbSNP:rs104894322EnsemblClinVar.1
Natural variantiVAR_013778151F → S in HIGM2. 2 PublicationsCorresponds to variant dbSNP:rs104894327EnsemblClinVar.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
ProteomicsDBi80168

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 Expressed in 68 organ(s), highest expression level in chorionic villus
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi121497, 54 interactors
DIPiDIP-48519N
ELMiQ9GZX7
IntActiQ9GZX7, 30 interactors
MINTiQ9GZX7
STRINGi9606.ENSP00000229335

Structurei

Secondary structure

1198
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiGYPNLSL
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

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YGF6H0YGF6_HUMAN
Single-stranded DNA cytosine deamin...
AICDA
197Annotation score:
H0YFL3H0YFL3_HUMAN
Single-stranded DNA cytosine deamin...
AICDA
144Annotation score:
H0YFP1H0YFP1_HUMAN
Single-stranded DNA cytosine deamin...
AICDA
68Annotation score:

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:rs104894324EnsemblClinVar.1
Natural variantiVAR_01409125R → C1 PublicationCorresponds to variant dbSNP:rs1404944797Ensembl.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:rs104894320EnsemblClinVar.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:rs104894321EnsemblClinVar.1
Natural variantiVAR_077567130H → P in HIGM2; slightly decreased mutagenic activity. 2 Publications1
Natural variantiVAR_013777139M → V in HIGM2. 2 PublicationsCorresponds to variant dbSNP:rs104894322EnsemblClinVar.1
Natural variantiVAR_013778151F → S in HIGM2. 2 PublicationsCorresponds to variant dbSNP:rs104894327EnsemblClinVar.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

Cross-referencesi

Web resourcesi

AICDAbase

AICDA mutation db

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5JJ4X-ray2.81A/B/C23-183[»]
5W0RX-ray2.40A/B13-181[»]
5W0UX-ray2.90A/B13-181[»]
5W0ZX-ray3.61A/B13-181[»]
5W1CX-ray3.18A/B5-181[»]
ProteinModelPortaliQ9GZX7
SMRiQ9GZX7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121497, 54 interactors
DIPiDIP-48519N
ELMiQ9GZX7
IntActiQ9GZX7, 30 interactors
MINTiQ9GZX7
STRINGi9606.ENSP00000229335

PTM databases

iPTMnetiQ9GZX7
PhosphoSitePlusiQ9GZX7

Polymorphism and mutation databases

BioMutaiAICDA
DMDMi23813666

Proteomic databases

MaxQBiQ9GZX7
PaxDbiQ9GZX7
PeptideAtlasiQ9GZX7
PRIDEiQ9GZX7
ProteomicsDBi80168

Protocols and materials databases

DNASUi57379
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi57379
DisGeNETi57379
EuPathDBiHostDB:ENSG00000111732.10
GeneCardsiAICDA
HGNCiHGNC:13203 AICDA
MalaCardsiAICDA
MIMi605257 gene
605258 phenotype
neXtProtiNX_Q9GZX7
OpenTargetsiENSG00000111732
Orphaneti101089 Hyper-IgM syndrome type 2
PharmGKBiPA24644
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BRENDAi3.5.4.38 2681
SIGNORiQ9GZX7

Miscellaneous databases

GeneWikiiAICDA
GenomeRNAii57379
PROiPR:Q9GZX7
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000111732 Expressed in 68 organ(s), highest expression level in chorionic villus
CleanExiHS_AICDA
ExpressionAtlasiQ9GZX7 baseline and differential
GenevisibleiQ9GZX7 HS

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
ProtoNetiSearch...

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: November 7, 2018
This is version 157 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
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