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UniProtKB/Swiss-Prot P84243: Variant p.Lys28Met

Histone H3.3
Gene: H3-3B
Variant information

Variant position:  28
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 Lysine (K) to Methionine (M) at position 28 (K28M, p.Lys28Met).
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 basic (K) to medium size and hydrophobic (M)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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 GLM; glioblastoma multiforme samples and diffuse intrinsic pontine glioma; somatic mutation; more prevalent in pediatric than adult malignancies; results in reduced allosteric activation of PRC2 causing a global decrease of H3K27me3 levels; has no effect on H3K4me3 or H3K36me3 levels.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  28
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  136
The length of the canonical sequence.

Location on the sequence:   ARKSTGGKAPRKQLATKAAR  K SAPSTGGVKKPHRYRPGTVA
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.

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.

TypePositionsDescription
Chain 2 – 136 Histone H3.3
Site 32 – 32 Interaction with ZMYND11
Modified residue 9 – 9 Citrulline; alternate
Modified residue 9 – 9 Symmetric dimethylarginine; by PRMT5; alternate
Modified residue 10 – 10 N6,N6,N6-trimethyllysine; alternate
Modified residue 10 – 10 N6,N6-dimethyllysine; alternate
Modified residue 10 – 10 N6-(2-hydroxyisobutyryl)lysine; alternate
Modified residue 10 – 10 N6-(beta-hydroxybutyryl)lysine; alternate
Modified residue 10 – 10 N6-acetyllysine; alternate
Modified residue 10 – 10 N6-butyryllysine; alternate
Modified residue 10 – 10 N6-crotonyllysine; alternate
Modified residue 10 – 10 N6-lactoyllysine; alternate
Modified residue 10 – 10 N6-methyllysine; alternate
Modified residue 11 – 11 ADP-ribosylserine; alternate
Modified residue 11 – 11 Phosphoserine; alternate; by AURKB, AURKC, RPS6KA3, RPS6KA4 and RPS6KA5
Modified residue 12 – 12 Phosphothreonine; by PKC
Modified residue 15 – 15 N6-(2-hydroxyisobutyryl)lysine; alternate
Modified residue 15 – 15 N6-(beta-hydroxybutyryl)lysine; alternate
Modified residue 15 – 15 N6-acetyllysine; alternate
Modified residue 15 – 15 N6-glutaryllysine; alternate
Modified residue 15 – 15 N6-lactoyllysine; alternate
Modified residue 15 – 15 N6-succinyllysine; alternate
Modified residue 18 – 18 Asymmetric dimethylarginine; by CARM1; alternate
Modified residue 18 – 18 Citrulline; alternate
Modified residue 19 – 19 N6-(2-hydroxyisobutyryl)lysine; alternate
Modified residue 19 – 19 N6-(beta-hydroxybutyryl)lysine; alternate
Modified residue 19 – 19 N6-acetyllysine; alternate
Modified residue 19 – 19 N6-butyryllysine; alternate
Modified residue 19 – 19 N6-crotonyllysine; alternate
Modified residue 19 – 19 N6-glutaryllysine; alternate
Modified residue 19 – 19 N6-lactoyllysine; alternate
Modified residue 19 – 19 N6-methyllysine; alternate
Modified residue 24 – 24 N6-(2-hydroxyisobutyryl)lysine; alternate
Modified residue 24 – 24 N6-(beta-hydroxybutyryl)lysine; alternate
Modified residue 24 – 24 N6-acetyllysine; alternate
Modified residue 24 – 24 N6-butyryllysine; alternate
Modified residue 24 – 24 N6-crotonyllysine; alternate
Modified residue 24 – 24 N6-glutaryllysine; alternate
Modified residue 24 – 24 N6-lactoyllysine; alternate
Modified residue 24 – 24 N6-methyllysine; alternate
Modified residue 27 – 27 Citrulline
Modified residue 28 – 28 N6,N6,N6-trimethyllysine; alternate
Modified residue 28 – 28 N6,N6-dimethyllysine; alternate
Modified residue 28 – 28 N6-(2-hydroxyisobutyryl)lysine; alternate
Modified residue 28 – 28 N6-(beta-hydroxybutyryl)lysine; alternate
Modified residue 28 – 28 N6-acetyllysine; alternate
Modified residue 28 – 28 N6-crotonyllysine; alternate
Modified residue 28 – 28 N6-glutaryllysine; alternate
Modified residue 28 – 28 N6-lactoyllysine; alternate
Modified residue 28 – 28 N6-methyllysine; alternate
Modified residue 29 – 29 ADP-ribosylserine; alternate
Modified residue 29 – 29 Phosphoserine; alternate; by AURKB, AURKC and RPS6KA5
Modified residue 32 – 32 Phosphoserine
Modified residue 37 – 37 N6,N6,N6-trimethyllysine; alternate
Modified residue 37 – 37 N6,N6-dimethyllysine; alternate
Modified residue 37 – 37 N6-(2-hydroxyisobutyryl)lysine; alternate
Modified residue 37 – 37 N6-acetyllysine; alternate
Modified residue 37 – 37 N6-methyllysine; alternate
Modified residue 38 – 38 N6-methyllysine
Modified residue 42 – 42 Phosphotyrosine
Mutagenesis 43 – 43 R -> K. Reduced binding of histone H1 to histone H3.3-containing nucleosomes.


Literature citations

Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas.
Wu G.; Broniscer A.; McEachron T.A.; Lu C.; Paugh B.S.; Becksfort J.; Qu C.; Ding L.; Huether R.; Parker M.; Zhang J.; Gajjar A.; Dyer M.A.; Mullighan C.G.; Gilbertson R.J.; Mardis E.R.; Wilson R.K.; Downing J.R.; Ellison D.W.; Zhang J.; Baker S.J.;
Nat. Genet. 44:251-253(2012)
Cited for: INVOLVEMENT IN GLM; VARIANT GLM MET-28;

Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma.
Schwartzentruber J.; Korshunov A.; Liu X.Y.; Jones D.T.; Pfaff E.; Jacob K.; Sturm D.; Fontebasso A.M.; Quang D.A.; Toenjes M.; Hovestadt V.; Albrecht S.; Kool M.; Nantel A.; Konermann C.; Lindroth A.; Jaeger N.; Rausch T.; Ryzhova M.; Korbel J.O.; Hielscher T.; Hauser P.; Garami M.; Klekner A.; Bognar L.; Ebinger M.; Schuhmann M.U.; Scheurlen W.; Pekrun A.; Fruehwald M.C.; Roggendorf W.; Kramm C.; Duerken M.; Atkinson J.; Lepage P.; Montpetit A.; Zakrzewska M.; Zakrzewski K.; Liberski P.P.; Dong Z.; Siegel P.; Kulozik A.E.; Zapatka M.; Guha A.; Malkin D.; Felsberg J.; Reifenberger G.; von Deimling A.; Ichimura K.; Collins V.P.; Witt H.; Milde T.; Witt O.; Zhang C.; Castelo-Branco P.; Lichter P.; Faury D.; Tabori U.; Plass C.; Majewski J.; Pfister S.M.; Jabado N.;
Nature 482:226-231(2012)
Cited for: INVOLVEMENT IN GLM; VARIANTS GLM MET-28; ARG-35 AND VAL-35;

The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression.
Chan K.M.; Fang D.; Gan H.; Hashizume R.; Yu C.; Schroeder M.; Gupta N.; Mueller S.; James C.D.; Jenkins R.; Sarkaria J.; Zhang Z.;
Genes Dev. 27:985-990(2013)
Cited for: CHARACTERIZATION OF VARIANT GLM MET-28;

Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma.
Lewis P.W.; Mueller M.M.; Koletsky M.S.; Cordero F.; Lin S.; Banaszynski L.A.; Garcia B.A.; Muir T.W.; Becher O.J.; Allis C.D.;
Science 340:857-861(2013)
Cited for: CHARACTERIZATION OF VARIANTS GLM MET-28; ARG-35 AND VAL-35;

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.