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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9UHD2: Variant p.Glu696Lys

Serine/threonine-protein kinase TBK1
Gene: TBK1
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Variant information Variant position: help 696 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 Glutamate (E) to Lysine (K) at position 696 (E696K, p.Glu696Lys). 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 medium size and acidic (E) to large size and basic (K) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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: help In FTDALS4; loss of kinase activity; impairs binding to OPTN. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 696 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 729 The length of the canonical sequence.
Location on the sequence: help IYPSSNTLVEMTLGMKKLKE E MEGVVKELAENNHILERFGS 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                         IYPSSNTLVEMTLGMKKLKEEMEGVVKELAENNHILERFGS

Mouse                         IYPSSNTLVEMTLGMKKLKEEMEGVVKELAENNHILERFGS

Xenopus laevis                IYSSPNTLVEMTLGMRKLKEDMEGVVKELEENNHILERFGA
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 – 729 Serine/threonine-protein kinase TBK1
Region 621 – 729 Interaction with AZI2, TANK and TBKBP1
Coiled coil 658 – 713
Modified residue 716 – 716 Phosphoserine
Mutagenesis 690 – 690 M -> A. Decreases interaction with TANK.
Mutagenesis 693 – 693 L -> A. Almost abolishes interaction with TANK.
Mutagenesis 694 – 694 K -> E. Strongly decreases interaction with TANK and TBKBP1. No effect on phosphorylation.
Mutagenesis 704 – 704 L -> A. Strongly decreases interaction with AZI2, TANK and TBKBP1. No effect on phosphorylation.
Mutagenesis 708 – 708 N -> A. Decreases interaction with TANK.
Mutagenesis 711 – 711 L -> A. Almost abolishes interaction with TANK.
Helix 680 – 714



Literature citations
Whole-genome sequencing reveals important role for TBK1 and OPTN mutations in frontotemporal lobar degeneration without motor neuron disease.
Pottier C.; Bieniek K.F.; Finch N.; van de Vorst M.; Baker M.; Perkersen R.; Brown P.; Ravenscroft T.; van Blitterswijk M.; Nicholson A.M.; DeTure M.; Knopman D.S.; Josephs K.A.; Parisi J.E.; Petersen R.C.; Boylan K.B.; Boeve B.F.; Graff-Radford N.R.; Veltman J.A.; Gilissen C.; Murray M.E.; Dickson D.W.; Rademakers R.;
Acta Neuropathol. 130:77-92(2015)
Cited for: INVOLVEMENT IN FTDALS4; VARIANTS FTDALS4 ILE-306; GLU-401 AND LYS-696; Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia.
Freischmidt A.; Wieland T.; Richter B.; Ruf W.; Schaeffer V.; Mueller K.; Marroquin N.; Nordin F.; Huebers A.; Weydt P.; Pinto S.; Press R.; Millecamps S.; Molko N.; Bernard E.; Desnuelle C.; Soriani M.H.; Dorst J.; Graf E.; Nordstroem U.; Feiler M.S.; Putz S.; Boeckers T.M.; Meyer T.; Winkler A.S.; Winkelman J.; de Carvalho M.; Thal D.R.; Otto M.; Braennstroem T.; Volk A.E.; Kursula P.; Danzer K.M.; Lichtner P.; Dikic I.; Meitinger T.; Ludolph A.C.; Strom T.M.; Andersen P.M.; Weishaupt J.H.;
Nat. Neurosci. 18:631-636(2015)
Cited for: INVOLVEMENT IN FTDALS4; VARIANTS FTDALS4 HIS-47; CYS-105; THR-305; GLN-308; GLN-357; ARG-559; VAL-571; VAL-598; GLU-643 DEL AND LYS-696; CHARACTERIZATION OF VARIANTS FTDALS4 HIS-47; GLN-308; GLN-357; ARG-559 AND LYS-696;
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.