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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q86UE8: Variant p.Ser617Leu

Serine/threonine-protein kinase tousled-like 2
Gene: TLK2
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Variant information Variant position: help 617 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Serine (S) to Leucine (L) at position 617 (S617L, p.Ser617Leu). 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: help Change from small size and polar (S) to medium size and hydrophobic (L) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In MRD57; exhibits abnormal perinuclear localization instead of diffuse nuclear localization; impairs kinase activity; reduced phosphorylation of ASF1A. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 617 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 772 The length of the canonical sequence.
Location on the sequence: help NILLVNGTACGEIKITDFGL S KIMDDDSYNSVDGMELTSQG 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         NILLVNGTACGEIKITDFGLSKIMDDDSYNSVDGMELTSQG

Mouse                         NILLVNGTACGEIKITDFGLSKIMDDDSYNSVDGMELTSQG

Xenopus tropicalis            NILLVNGTACGEIKITDFGLSKIMDDDSYNSVDGMELTSQG

Zebrafish                     NILLVNGTACGEIKITDFGLSKIMDDDNY-GVDGMELTSQG
Sequence annotation in neighborhood: help 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 1 – 772 Serine/threonine-protein kinase tousled-like 2
Domain 462 – 741 Protein kinase
Mutagenesis 613 – 613 D -> A. Loss of kinase activity.
Mutagenesis 617 – 617 S -> A. Increase in autophosphorylation.
Mutagenesis 617 – 617 S -> D. Loss of kinase activity.



Literature citations
Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.
O'Roak B.J.; Deriziotis P.; Lee C.; Vives L.; Schwartz J.J.; Girirajan S.; Karakoc E.; Mackenzie A.P.; Ng S.B.; Baker C.; Rieder M.J.; Nickerson D.A.; Bernier R.; Fisher S.E.; Shendure J.; Eichler E.E.;
Nat. Genet. 43:585-589(2011)
Cited for: VARIANT MRD57 LEU-617; Functional analysis of TLK2 variants and their proximal interactomes implicates impaired kinase activity and chromatin maintenance defects in their pathogenesis.
Pavinato L.; Villamor-Paya M.; Sanchiz-Calvo M.; Andreoli C.; Gay M.; Vilaseca M.; Arauz-Garofalo G.; Ciolfi A.; Bruselles A.; Pippucci T.; Prota V.; Carli D.; Giorgio E.; Radio F.C.; Antona V.; Giuffre M.; Ranguin K.; Colson C.; De Rubeis S.; Dimartino P.; Buxbaum J.D.; Ferrero G.B.; Tartaglia M.; Martinelli S.; Stracker T.H.; Brusco A.;
J. Med. Genet. 59:170-179(2022)
Cited for: VARIANTS MRD57 475-GLU--ASN-772 DEL AND GLY-551; CHARACTERIZATION OF VARIANTS MRD57 GLY-551 AND LEU-617; FUNCTION; SUBCELLULAR LOCATION; INTERACTION WITH TLK1; CHD7; CHD8 AND DYNLL1/LC8; MUTAGENESIS OF ASP-592;
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.