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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13501: Variant p.Gly411Ser

Sequestosome-1
Gene: SQSTM1
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Variant information Variant position: help 411 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 Glycine (G) to Serine (S) at position 411 (G411S, p.Gly411Ser). 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 glycine (G) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 0 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 PDB3 and FTDALS3; no effect on polyubiquitin-binding; decreased ability to undergo liquid-liquid phase separation and formation of p62 body. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 411 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 440 The length of the canonical sequence.
Location on the sequence: help DPRLIESLSQMLSMGFSDEG G WLTRLLQTKNYDIGAALDTI 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                         DPRLIESLSQMLSMGFSDEGGWLTRLLQTKNYDIGAALDTI

Mouse                         DPRLIESLSQMLSMGFSDEGGWLTRLLQTKNYDIGAALDTI

Rat                           DPRLIESLSQMLSMGFSDEGGWLTRLLQTKNYDIGAALDTI
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 2 – 440 Sequestosome-1
Domain 389 – 434 UBA
Region 269 – 440 Interaction with NTRK1
Modified residue 403 – 403 Phosphoserine; by CK2, ULK1 and TBK1
Modified residue 407 – 407 Phosphoserine; by ULK1
Modified residue 420 – 420 N6-acetyllysine; alternate
Cross 420 – 420 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Mutagenesis 398 – 398 L -> V. No effect on polyubiquitin-binding.
Mutagenesis 403 – 403 S -> A. Abolished phosphorylation by CK2, leading to decreased affinity for ubiquitinated proteins. Abolished ability to promote relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes.
Mutagenesis 403 – 403 S -> E. Mimmics phosphorylation; increased affinity for ubiquitinated proteins, leading to increased p62 body formation and autophagic degradation.
Mutagenesis 406 – 406 F -> V. Loss of polyubiquitin-binding.
Mutagenesis 409 – 409 E -> K. Decreased activation of NF-kappa-B.
Mutagenesis 410 – 410 G -> K. Decreased activation of NF-kappa-B.
Mutagenesis 413 – 413 L -> V. No effect on polyubiquitin-binding.
Mutagenesis 417 – 417 L -> V. Loss of polyubiquitin-binding.
Mutagenesis 420 – 420 K -> Q. Mimics acetylation; leading to increased ability to bind ubiquitinated proteins; when associated with Q-435.
Mutagenesis 420 – 420 K -> R. Decreased ubiquitination by the BCR(KEAP1) complex, leading to decreased sequestering activity. Strongly reduced acetylation; when associated with R-435.
Mutagenesis 431 – 431 I -> V. Partial loss of polyubiquitin-binding. Loss of localization to cytoplasmic inclusion bodies.
Beta strand 409 – 411



Literature citations
SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis.
Fecto F.; Yan J.; Vemula S.P.; Liu E.; Yang Y.; Chen W.; Zheng J.G.; Shi Y.; Siddique N.; Arrat H.; Donkervoort S.; Ajroud-Driss S.; Sufit R.L.; Heller S.L.; Deng H.X.; Siddique T.;
Arch. Neurol. 68:1440-1446(2011)
Cited for: INVOLVEMENT IN FTDALS3; VARIANTS FTDALS3 VAL-33; ILE-153; LEU-228; LYS-238 DEL; PRO-318; CYS-321; PRO-370; LEU-392; SER-411 AND ARG-425; Polyubiquitin chain-induced p62 phase separation drives autophagic cargo segregation.
Sun D.; Wu R.; Zheng J.; Li P.; Yu L.;
Cell Res. 28:405-415(2018)
Cited for: FUNCTION; SUBCELLULAR LOCATION; PHOSPHORYLATION AT SER-403; MUTAGENESIS OF SER-403; CHARACTERIZATION OF VARIANTS PDB3 THR-404 AND SER-411; Novel UBA domain mutations of SQSTM1 in Paget's disease of bone: genotype phenotype correlation, functional analysis, and structural consequences.
Hocking L.J.; Lucas G.J.A.; Daroszewska A.; Cundy T.; Nicholson G.C.; Donath J.; Walsh J.P.; Finlayson C.; Cavey J.R.; Ciani B.; Sheppard P.W.; Searle M.S.; Layfield R.; Ralston S.H.;
J. Bone Miner. Res. 19:1122-1127(2004)
Cited for: VARIANTS PDB3 VAL-404; SER-411 AND ARG-425; CHARACTERIZATION OF VARIANTS VAL-404; SER-411 AND ARG-425;
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.