UniProtKB/Swiss-Prot Q15910: Variant p.Ala677Gly

Histone-lysine N-methyltransferase EZH2
Gene: EZH2
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Variant information Variant position:

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

LB/B 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 Alanine (A) to Glycine (G) at position 677 (A677G, p.Ala677Gly). 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 small size and hydrophobic (A) to glycine (G) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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 a patient with B-cell lymphoma; increased hypertrimethylation of H3K27; changed substrate preferences; confers biochemical activity independent of H3K27 methylation state. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1057519833 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

VYDKYMCSFLFNLNNDFVVD A TRKGNKIRFANHSVNPNCYA 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                         VYDKYMCSFLFNLNNDFVVDATRKGNKIRFANHSVNPNCYA

Mouse                         VYDKYMCSFLFNLNNDFVVDATRKGNKIRFANHSVNPNCYA

Xenopus tropicalis            VYDKYMCSFLFNLNNDFVVDATRKGNKIRFANHSVNPNCYA

Zebrafish                     VYDKYMCSFLFNLNNDFVVDATRKGNKIRFANHSVNPNCYA

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 – 746	Histone-lysine N-methyltransferase EZH2
Domain	612 – 727	SET
Mutagenesis	667 – 667	F -> I. Strongly decreases histone methyltransferase activity.
Mutagenesis	689 – 689	H -> A. Abrogates methyltransferase activity.

Literature citations
Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27).
McCabe M.T.; Graves A.P.; Ganji G.; Diaz E.; Halsey W.S.; Jiang Y.; Smitheman K.N.; Ott H.M.; Pappalardi M.B.; Allen K.E.; Chen S.B.; Della Pietra A. III; Dul E.; Hughes A.M.; Gilbert S.A.; Thrall S.H.; Tummino P.J.; Kruger R.G.; Brandt M.; Schwartz B.; Creasy C.L.;
Proc. Natl. Acad. Sci. U.S.A. 109:2989-2994(2012)
Cited for: VARIANT GLY-677; CHARACTERIZATION OF VARIANTS ASN-641; CYS-641; HIS-641; PHE-641 AND GLY-677; FUNCTION; CATALYTIC ACTIVITY;

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.