Q9GZX7 · AICDA_HUMAN
- ProteinSingle-stranded DNA cytosine deaminase
- GeneAICDA
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids198 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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).
May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation (PubMed:21496894).
Catalytic activity
- a 2'-deoxycytidine in single-stranded DNA + H+ + H2O = a 2'-deoxyuridine in single-stranded DNA + NH4+
Cofactor
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSingle-stranded DNA cytosine deaminase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9GZX7
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Predominantly cytosolic (PubMed:21385873).
In the presence of MCM3AP/GANP, relocalizes to the nucleus (By similarity).
In the presence of MCM3AP/GANP, relocalizes to the nucleus (By similarity).
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Immunodeficiency with hyper-IgM 2 (HIGM2)
- Note
- 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 alsoMIM:605258
Natural variants in HIGM2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_077563 | 15 | F>L | in HIGM2; dbSNP:rs2136433362 and dbSNP:rs2136433359 | |
VAR_013774 | 24 | R>W | in HIGM2; completely abolishes nuclear import and interaction with CTNNBL1, diminishes interaction with KPNA1 and abolishes immunoglobulin class switching; dbSNP:rs104894324 | |
VAR_077564 | 31 | Y>H | in HIGM2 | |
VAR_077565 | 56 | H>Y | in HIGM2; uncertain significance; loss of mutagenic activity | |
VAR_013775 | 80 | W>R | in HIGM2; dbSNP:rs104894320 | |
VAR_077566 | 87 | C>R | in HIGM2; uncertain significance; dbSNP:rs762590894 | |
VAR_013776 | 106 | L>P | in HIGM2; dbSNP:rs104894321 | |
VAR_077567 | 130 | H>P | in HIGM2; slightly decreased mutagenic activity | |
VAR_013777 | 139 | M>V | in HIGM2; dbSNP:rs104894322 | |
VAR_013778 | 151 | F>S | in HIGM2; dbSNP:rs104894327 | |
VAR_077568 | 174 | R>S | in HIGM2; uncertain significance |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 10 | Little effect on nuclear import; when associated with A-193. No effect on CTNNBL1 binding. | ||||
Sequence: K → A | ||||||
Natural variant | VAR_077563 | 15 | in HIGM2; dbSNP:rs2136433362 and dbSNP:rs2136433359 | |||
Sequence: F → L | ||||||
Mutagenesis | 18 | 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. | ||||
Sequence: V → S | ||||||
Mutagenesis | 19 | 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. | ||||
Sequence: R → V | ||||||
Mutagenesis | 20 | Impaired nuclear import; when associated with A-193. No effect on CTNNBL1 binding. | ||||
Sequence: W → K | ||||||
Natural variant | VAR_013774 | 24 | in HIGM2; completely abolishes nuclear import and interaction with CTNNBL1, diminishes interaction with KPNA1 and abolishes immunoglobulin class switching; dbSNP:rs104894324 | |||
Sequence: R → W | ||||||
Natural variant | VAR_014091 | 25 | in dbSNP:rs1404944797 | |||
Sequence: R → C | ||||||
Mutagenesis | 27 | Loss of phosphorylation. No effect on cytidine deaminase activity. Impaired class-switch recombination activity. | ||||
Sequence: T → A | ||||||
Mutagenesis | 27 | Phosphomimetic mutant which shows loss of cytidine deaminase activity and impaired class-switch recombination activity. | ||||
Sequence: T → E | ||||||
Natural variant | VAR_077564 | 31 | in HIGM2 | |||
Sequence: Y → H | ||||||
Mutagenesis | 38 | Loss of phosphorylation. Impaired class-switch recombination activity. No effect on interaction with CTNNBL1. | ||||
Sequence: S → A | ||||||
Mutagenesis | 38 | No effect on interaction with CTNNBL1. | ||||
Sequence: S → D | ||||||
Mutagenesis | 39-42 | 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. | ||||
Sequence: ATSF → GGQV | ||||||
Mutagenesis | 50 | Some reduced nuclear import; when associated with A-193. | ||||
Sequence: R → G | ||||||
Natural variant | VAR_077565 | 56 | in HIGM2; uncertain significance; loss of mutagenic activity | |||
Sequence: H → Y | ||||||
Natural variant | VAR_013775 | 80 | in HIGM2; dbSNP:rs104894320 | |||
Sequence: W → R | ||||||
Natural variant | VAR_077566 | 87 | in HIGM2; uncertain significance; dbSNP:rs762590894 | |||
Sequence: C → R | ||||||
Natural variant | VAR_013776 | 106 | in HIGM2; dbSNP:rs104894321 | |||
Sequence: L → P | ||||||
Mutagenesis | 112 | Greatly reduced nuclear import; when associated with A-193. | ||||
Sequence: R → D | ||||||
Natural variant | VAR_077567 | 130 | in HIGM2; slightly decreased mutagenic activity | |||
Sequence: H → P | ||||||
Natural variant | VAR_013777 | 139 | in HIGM2; dbSNP:rs104894322 | |||
Sequence: M → V | ||||||
Natural variant | VAR_013778 | 151 | in HIGM2; dbSNP:rs104894327 | |||
Sequence: F → S | ||||||
Natural variant | VAR_077568 | 174 | in HIGM2; uncertain significance | |||
Sequence: R → S | ||||||
Mutagenesis | 193 | 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. | ||||
Sequence: F → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 266 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000171687 | 1-198 | Single-stranded DNA cytosine deaminase | |||
Sequence: MDSLLMNRRKFLYQFKNVRWAKGRRETYLCYVVKRRDSATSFSLDFGYLRNKNGCHVELLFLRYISDWDLDPGRCYRVTWFTSWSPCYDCARHVADFLRGNPNLSLRIFTARLYFCEDRKAEPEGLRRLHRAGVQIAIMTFKDYFYCWNTFVENHERTFKAWEGLHENSVRLSRQLRRILLPLYEVDDLRDAFRTLGL | ||||||
Modified residue | 27 | Phosphothreonine; by PKA | ||||
Sequence: T | ||||||
Modified residue | 38 | Phosphoserine; by PKA | ||||
Sequence: S |
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.
Probably monoubiquitinated on several residues by RNF126.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Strongly expressed in lymph nodes and tonsils.
Induction
Negatively regulated by microRNA-155 (miR-155).
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with CTNNBL1; the interaction is important for the immunoglobulin switch activity of AICDA (PubMed:18722174, PubMed:21385873, PubMed:32484799).
Interacts (via its NLS) with KPNA1. Interacts with PKA/PRKACA and PRKAR1A/PKR1 (PubMed:16387847).
Interacts with TRIM28 and NCL (By similarity).
Interacts with SUPT6H (PubMed:21518874).
Interacts with RNF126 (PubMed:23277564).
Directly interacts with MCM3AP; this interaction may favor AICDA recruitment to immunoglobulin variable region genes, hence promoting somatic hypermutations (PubMed:20507984).
Interacts (via its NLS) with KPNA1. Interacts with PKA/PRKACA and PRKAR1A/PKR1 (PubMed:16387847).
Interacts with TRIM28 and NCL (By similarity).
Interacts with SUPT6H (PubMed:21518874).
Interacts with RNF126 (PubMed:23277564).
Directly interacts with MCM3AP; this interaction may favor AICDA recruitment to immunoglobulin variable region genes, hence promoting somatic hypermutations (PubMed:20507984).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9GZX7 | AICDA Q9GZX7 | 2 | EBI-3834328, EBI-3834328 | |
XENO | Q9GZX7 | C Q784Z8 | 2 | EBI-3834328, EBI-11666471 | |
BINARY | Q9GZX7 | DNAJA1 P31689 | 6 | EBI-3834328, EBI-347834 | |
BINARY | Q9GZX7 | DNAJA2 O60884 | 3 | EBI-3834328, EBI-352957 | |
BINARY | Q9GZX7 | GADD45A P24522 | 5 | EBI-3834328, EBI-448167 | |
BINARY | Q9GZX7 | HSPA8 P11142 | 2 | EBI-3834328, EBI-351896 | |
BINARY | Q9GZX7 | KPNA1 P52294 | 2 | EBI-3834328, EBI-358383 | |
BINARY | Q9GZX7 | KPNA3 O00505 | 2 | EBI-3834328, EBI-358297 | |
BINARY | Q9GZX7 | KPNA5 O15131 | 2 | EBI-3834328, EBI-540602 | |
BINARY | Q9GZX7 | PRKACA P17612 | 3 | EBI-3834328, EBI-476586 | |
BINARY | Q9GZX7 | PRKAR1A P10644 | 5 | EBI-3834328, EBI-476431 | |
BINARY | Q9GZX7 | TDG Q13569 | 5 | EBI-3834328, EBI-348333 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif, region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 1-30 | Bipartite nuclear localization signal | ||||
Sequence: MDSLLMNRRKFLYQFKNVRWAKGRRETYLC | ||||||
Region | 2-26 | Interaction with SUPT6H | ||||
Sequence: DSLLMNRRKFLYQFKNVRWAKGRRE | ||||||
Domain | 23-129 | CMP/dCMP-type deaminase | ||||
Sequence: GRRETYLCYVVKRRDSATSFSLDFGYLRNKNGCHVELLFLRYISDWDLDPGRCYRVTWFTSWSPCYDCARHVADFLRGNPNLSLRIFTARLYFCEDRKAEPEGLRRL | ||||||
Region | 39-42 | Important for interaction with CTNNBL1 | ||||
Sequence: ATSF | ||||||
Region | 88-116 | Required for interaction with RNF126 | ||||
Sequence: YDCARHVADFLRGNPNLSLRIFTARLYFC | ||||||
Motif | 183-198 | Nuclear export signal | ||||
Sequence: LYEVDDLRDAFRTLGL |
Sequence similarities
Belongs to the cytidine and deoxycytidylate deaminase family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
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.
- Name1
- Length198
- Mass (Da)23,954
- Last updated2001-03-01 v1
- Checksum3C27BB143DB184A9
Q9GZX7-2
- Name2
- Differences from canonical
- 143-152: Missing
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8Q3WL45 | A0A8Q3WL45_HUMAN | AICDA | 183 | ||
A0A8Q3SIK8 | A0A8Q3SIK8_HUMAN | AICDA | 209 | ||
A0A8Q3SII6 | A0A8Q3SII6_HUMAN | AICDA | 193 | ||
Q6QJ80 | Q6QJ80_HUMAN | AICDA | 145 | ||
Q6QLN7 | Q6QLN7_HUMAN | AICDA | 69 |
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 119 | in Ref. 3; AAM95406 | ||||
Sequence: R → H | ||||||
Alternative sequence | VSP_047803 | 143-152 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB040431 EMBL· GenBank· DDBJ | BAB12721.1 EMBL· GenBank· DDBJ | mRNA | ||
AB040430 EMBL· GenBank· DDBJ | BAB12720.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF529819 EMBL· GenBank· DDBJ | AAM95406.1 EMBL· GenBank· DDBJ | mRNA | ||
AY536516 EMBL· GenBank· DDBJ | AAS92920.1 EMBL· GenBank· DDBJ | mRNA | ||
BT007402 EMBL· GenBank· DDBJ | AAP36066.1 EMBL· GenBank· DDBJ | mRNA | ||
AC092184 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC006296 EMBL· GenBank· DDBJ | AAH06296.1 EMBL· GenBank· DDBJ | mRNA |