UniProtKB/Swiss-Prot Q13501: Variant p.Pro387Leu

Gene: SQSTM1
Chromosomal location: 5q35
Variant information

Variant position:  387
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  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:  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:  -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

Involvement in disease:  Paget disease of bone (PDB) [MIM:602080]: Metabolic bone disease affecting the axial skeleton and characterized by focal areas of increased and disorganized bone turn-over due to activated osteoclasts. Manifestations of the disease include bone pain, deformity, pathological fractures, deafness, neurological complications and increased risk of osteosarcoma. PDB is a chronic disease affecting 2 to 3% of the population above the age of 40 years. {ECO:0000269|PubMed:11992264, ECO:0000269|PubMed:12374763, ECO:0000269|PubMed:14584883, ECO:0000269|PubMed:15125799, ECO:0000269|PubMed:15146436, ECO:0000269|PubMed:15176995, ECO:0000269|PubMed:15207768}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In PDB.
Any additional useful information about the variant.

Sequence information

Variant position:  387
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  440
The length of the canonical sequence.

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: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.




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.

Chain 2 – 440 Sequestosome-1
Region 269 – 440 Interaction with NTRK1
Mutagenesis 398 – 398 L -> V. No effect on polyubiquitin-binding.
Mutagenesis 406 – 406 F -> V. Loss of polyubiquitin-binding.

Literature citations

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 PDB LEU-387;

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.