UniProtKB/Swiss-Prot Q86U44: Variant p.Tyr406Cys

N6-adenosine-methyltransferase catalytic subunit
Gene: METTL3
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Variant information Variant position:

406 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Cysteine (C) at position 406 (Y406C, p.Tyr406Cys). 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 (C) 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:

Found in patients with large intestine cancer; uncertain significance; does not affect interaction with METTL14; abolished RNA methyltransferase activity in vitro. Any additional useful information about the variant.

Sequence information Variant position:

406 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

580 The length of the canonical sequence.
Location on the sequence:

LGKFAVVMADPPWDIHMELP Y GTLTDDEMRRLNIPVLQDDG 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                         LGKFAVVMADPPWDIHMELPYGTLTDDEMRRLNIPVLQDDG

Mouse                         LGKFAVVMADPPWDIHMELPYGTLTDDEMRRLNIPVLQDDG

Zebrafish                     LGKFAVVMADPPWDIHMELPYGTLTDDEMRKLNIPILQDDG

Drosophila                    LGKFAVVMADPPWDIHMELPYGTMSDDEMRALGVPALQDDG

Baker's yeast                 LGKFSVVIADPAWNIHMNLPYGTCNDIELLGLPLHELQDEG

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	2 – 580	N6-adenosine-methyltransferase catalytic subunit
Region	396 – 410	Gate loop 1
Binding site	395 – 395
Mutagenesis	395 – 395	D -> A. Abolishes methyltransferase activity.
Mutagenesis	406 – 406	Y -> A. Strong reduction in methyltransferase activity.
Turn	405 – 407

Literature citations
Structural basis for cooperative function of Mettl3 and Mettl14 methyltransferases.
Wang P.; Doxtader K.A.; Nam Y.;
Mol. Cell 63:306-317(2016)
Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 357-580 IN COMPLEX WITH METTL14 AND S-ADENOSYL-L-METHIONINE; FUNCTION; CATALYTIC ACTIVITY; SUBUNIT; MUTAGENESIS OF CYS-294; CYS-326; ASP-395; TRP-475 AND ASN-477; VARIANT CYS-406; CHARACTERIZATION OF VARIANT CYS-406;

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.