Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9GZX7: Variant p.Arg24Trp

Single-stranded DNA cytosine deaminase
Gene: AICDA
Feedback?
Variant information Variant position: help 24 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Arginine (R) to Tryptophan (W) at position 24 (R24W, p.Arg24Trp). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Change from large size and basic (R) to large size and aromatic (W) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -3 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page
Variant description: help In HIGM2; completely abolishes nuclear import and interaction with CTNNBL1, diminishes interaction with KPNA1 and abolishes immunoglobulin class switching. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 24 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 198 The length of the canonical sequence.
Location on the sequence: help LLMNRRKFLYQFKNVRWAKG R RETYLCYVVKRRDSATSFSL The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         LLMNRRKFLYQFKNVRWAKGRRETYLCYVVKRRDSATSFSL

                              LLMKQRKFLYHFKNVRWAKGRHETYLCYVVKRRDSATSFSL

Mouse                         LLMKQKKFLYHFKNVRWAKGRHETYLCYVVKRRDSATSCSL

Bovine                        LLKKQRQFLYQFKNVRWAKGRHETYLCYVVKRRDSPTSFSL
Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 1 – 198 Single-stranded DNA cytosine deaminase
Domain 23 – 129 CMP/dCMP-type deaminase
Region 2 – 26 Interaction with SUPT6H
Motif 1 – 30 Bipartite nuclear localization signal
Modified residue 27 – 27 Phosphothreonine; by PKA
Modified residue 38 – 38 Phosphoserine; by PKA
Mutagenesis 10 – 10 K -> A. Little effect on nuclear import; when associated with A-193. No effect on CTNNBL1 binding.
Mutagenesis 18 – 18 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.
Mutagenesis 19 – 19 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.
Mutagenesis 20 – 20 W -> K. Impaired nuclear import; when associated with A-193. No effect on CTNNBL1 binding.
Mutagenesis 27 – 27 T -> A. Loss of phosphorylation. No effect on cytidine deaminase activity. Impaired class-switch recombination activity.
Mutagenesis 27 – 27 T -> E. Phosphomimetic mutant which shows loss of cytidine deaminase activity and impaired class-switch recombination activity.
Mutagenesis 38 – 38 S -> A. Loss of phosphorylation. Impaired class-switch recombination activity. No effect on interaction with CTNNBL1.
Mutagenesis 38 – 38 S -> D. No effect on interaction with CTNNBL1.



Literature citations
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.; Honjo T.; Fischer A.; Durandy A.;
Cell 102:565-575(2000)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1); VARIANTS HIGM2 TRP-24; ARG-80; PRO-106; VAL-139 AND SER-151; 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)
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; Clinical, immunologic and genetic analysis of 29 patients with autosomal recessive hyper-IgM syndrome due to activation-induced cytidine deaminase deficiency.
Quartier P.; Bustamante J.; Sanal O.; Plebani A.; Debre M.; Deville A.; Litzman J.; Levy J.; Fermand J.P.; Lane P.; Horneff G.; Aksu G.; Yalcin I.; Davies G.; Tezcan I.; Ersoy F.; Catalan N.; Imai K.; Fischer A.; Durandy A.;
Clin. Immunol. 110:22-29(2004)
Cited for: VARIANTS HIGM2 TRP-24; TYR-56; ARG-80; ARG-87; PRO-106; VAL-139; SER-151 AND SER-174;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.