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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13501: Variant p.Pro387Leu

Sequestosome-1
Gene: SQSTM1
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Variant information Variant position: help 387 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 Proline (P) to Leucine (L) at position 387 (P387L, p.Pro387Leu). 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 Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -3 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. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 387 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 LDPSQEGPTGLKEAALYPHL P PEADPRLIESLSQMLSMGFS 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                         LDPSQEGPTGLKEAALYPHLPPEADPRLIESLSQMLSMGFS

Mouse                         LDPSQEGPTGLKEAALYPHLPPEADPRLIESLSQMLSMGFS

Rat                           LDPSQEGPTGLKEAALYPHLPPEADPRLIESLSQMLSMGFS
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
Region 264 – 390 Disordered
Region 269 – 440 Interaction with NTRK1
Modified residue 403 – 403 Phosphoserine; by CK2, ULK1 and TBK1
Modified residue 407 – 407 Phosphoserine; by ULK1
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.



Literature citations
SQSTM1 mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis.
Le Ber I.; Camuzat A.; Guerreiro R.; Bouya-Ahmed K.; Bras J.; Nicolas G.; Gabelle A.; Didic M.; De Septenville A.; Millecamps S.; Lenglet T.; Latouche M.; Kabashi E.; Campion D.; Hannequin D.; Hardy J.; Brice A.;
JAMA Neurol. 70:1403-1410(2013)
Cited for: INVOLVEMENT IN FTDALS3; VARIANTS FTDALS3 VAL-33; VAL-381; LEU-387 AND LEU-392; Three novel mutations in SQSTM1 identified in familial Paget's disease of bone.
Johnson-Pais T.L.; Wisdom J.H.; Weldon K.S.; Cody J.D.; Hansen M.F.; Singer F.R.; Leach R.J.;
J. Bone Miner. Res. 18:1748-1753(2003)
Cited for: VARIANT PDB3 LEU-387; Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration.
van der Zee J.; Van Langenhove T.; Kovacs G.G.; Dillen L.; Deschamps W.; Engelborghs S.; Matej R.; Vandenbulcke M.; Sieben A.; Dermaut B.; Smets K.; Van Damme P.; Merlin C.; Laureys A.; Van Den Broeck M.; Mattheijssens M.; Peeters K.; Benussi L.; Binetti G.; Ghidoni R.; Borroni B.; Padovani A.; Archetti S.; Pastor P.; Razquin C.; Ortega-Cubero S.; Hernandez I.; Boada M.; Ruiz A.; de Mendonca A.; Miltenberger-Miltenyi G.; do Couto F.S.; Sorbi S.; Nacmias B.; Bagnoli S.; Graff C.; Chiang H.H.; Thonberg H.; Perneczky R.; Diehl-Schmid J.; Alexopoulos P.; Frisoni G.B.; Bonvicini C.; Synofzik M.; Maetzler W.; vom Hagen J.M.; Schoels L.; Haack T.B.; Strom T.M.; Prokisch H.; Dols-Icardo O.; Clarimon J.; Lleo A.; Santana I.; Almeida M.R.; Santiago B.; Heneka M.T.; Jessen F.; Ramirez A.; Sanchez-Valle R.; Llado A.; Gelpi E.; Sarafov S.; Tournev I.; Jordanova A.; Parobkova E.; Fabrizi G.M.; Testi S.; Salmon E.; Stroebel T.; Santens P.; Robberecht W.; De Jonghe P.; Martin J.J.; Cras P.; Vandenberghe R.; De Deyn P.P.; Cruts M.; Sleegers K.; Van Broeckhoven C.;
Acta Neuropathol. 128:397-410(2014)
Cited for: INVOLVEMENT IN FTDALS3; VARIANTS FTDALS3 VAL-16; VAL-33; GLU-80; MET-90; TRP-107; ASN-129; CYS-212; VAL-219; PRO-226; LEU-228; THR-232; LYS-238 DEL; ASN-258; CYS-321; GLY-329; LEU-348; LEU-387; LEU-392 AND PRO-430; VARIANTS VAL-17; ARG-103; GLN-107; TYR-108; HIS-110; VAL-117; SER-118; GLY-119; SER-125; CYS-139; ILE-153; LEU-180; HIS-217; GLU-238; 265-SER-ARG-266 DELINS SER-ARG; ASP-274; ILE-278; VAL-308; LYS-319; GLY-334 DEL; THR-349 AND LEU-439;
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.