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UniProtKB/Swiss-Prot P68431: Variant p.Lys28Met

Histone H3.1
Gene: H3C12
Variant information

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

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

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

Involvement in disease:  Glioma (GLM) [MIM:137800]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. {ECO:0000269|PubMed:22286216}. Note=The gene represented in this entry is involved in disease pathogenesis. HIST1H3B mutations affecting residue Lys-28 involved in post-translational modifications of histone H3.1 are recurrent in malignant, aggressive gliomas including pediatric non-brain stem glioblastoma and diffuse intrinsic pontine glioma (DIPG) (PubMed:22286216). The mechanism through which mutations lead to tumorigenesis involves altered histone methylation, impaired regulation of Polycomb repressive complex 2 (PRC2) activity, and aberrant epigenetic regulation of gene expression (PubMed:23603901). {ECO:0000269|PubMed:22286216, ECO:0000269|PubMed:23603901}.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In GLM; non-brain stem pediatric glioblastoma and diffuse intrinsic pontine glioma; somatic mutation; results in a global decrease of H3K27me3 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.

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.

Chain 2 – 136 Histone H3.1
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-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 and CHEK1
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-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-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-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-methyllysine; alternate
Modified residue 29 – 29 ADP-ribosylserine; alternate
Modified residue 29 – 29 Phosphoserine; alternate; by AURKB, AURKC and RPS6KA5
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

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)

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)

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.