UniProtKB/SwissProt variant VAR

Variant information

Variant position:

31

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:

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:

From Tyrosine (Y) to Histidine (H) at position 31 (Y31H, p.Tyr31His).

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:

Change from large size and aromatic (Y) to medium size and polar (H)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

2

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:

In HIGM2.

Any additional useful information about the variant.

Sequence information

Variant position:

31

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

198

The length of the canonical sequence.

Location on the sequence:

FLYQFKNVRWAKGRRETYLC Y VVKRRDSATSFSLDFGYLRN

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:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         FLYQFKNVRWAKGRRETYLCYVVKRRDSATSFSLDFGYLRN

                              FLYHFKNVRWAKGRHETYLCYVVKRRDSATSFSLDFGHLRN

Mouse                         FLYHFKNVRWAKGRHETYLCYVVKRRDSATSCSLDFGHLRN

Bovine                        FLYQFKNVRWAKGRHETYLCYVVKRRDSPTSFSLDFGHLRN

Sequence annotation in neighborhood:

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.

Type	Positions	Description
Chain	1 – 198	Single-stranded DNA cytosine deaminase
Domain	23 – 129	CMP/dCMP-type deaminase
Modified residue	27 – 27	Phosphothreonine; by PKA
Modified residue	38 – 38	Phosphoserine; by PKA
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.
Mutagenesis	50 – 50	R -> G. Some reduced nuclear import; when associated with A-193.
Beta strand	28 – 34

Literature citations

Novel and recurrent AID mutations underlie prevalent autosomal recessive form of HIGM in consanguineous patients.
Ouadani H.; Ben-Mustapha I.; Ben-ali M.; Ben-khemis L.; Largueche B.; Boussoffara R.; Maalej S.; Fetni I.; Hassayoun S.; Mahfoudh A.; Mellouli F.; Yalaoui S.; Masmoudi H.; Bejaoui M.; Barbouche M.R.;
Immunogenetics 68:19-28(2016)
Cited for: VARIANTS HIGM2 HIS-31 AND PRO-130;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9GZX7: Variant p.Tyr31His