UniProtKB/Swiss-Prot P84243: Variant p.Gly35Arg

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 35 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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 Glycine (G) to Arginine (R) at position 35 (G35R, p.Gly35Arg). 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 glycine (G) to large size and basic (R) 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 GLM; glioblastoma multiforme samples; somatic mutation; also found in osteosarcoma samples; results in global decrease of H3K36me2 and H3K36me3 levels; has no effect on H3K27me3 levels. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs1553260624 [ dbSNP | Ensembl ]

Sequence information

Variant position: 35 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: KAPRKQLATKAARKSAPSTG G VKKPHRYRPGTVALREIRRY 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.

Type	Positions	Description
Chain	2 – 136	Histone H3.3
Region	1 – 43	Disordered
Site	32 – 32	Interaction with ZMYND11
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
Lipidation	19 – 19	N6-decanoyllysine
Mutagenesis	43 – 43	R -> K. Reduced binding of histone H1 to histone H3.3-containing nucleosomes.
Beta strand	35 – 37

Literature citations

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: VARIANTS GLM MET-28; ARG-35 AND VAL-35; INVOLVEMENT IN GLM; 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;