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UniProtKB/Swiss-Prot P09936: Variant p.Ala216Asp

Ubiquitin carboxyl-terminal hydrolase isozyme L1
Gene: UCHL1
Variant information

Variant position:  216
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Alanine (A) to Aspartate (D) at position 216 (A216D, p.Ala216Asp).
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:  Change from small size and hydrophobic (A) to medium size and acidic (D)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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

Involvement in disease:  Spastic paraplegia 79, autosomal recessive (SPG79) [MIM:615491]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG79 is characterized by childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfunction, and spasticity with upper motor neuron dysfunction. {ECO:0000269|PubMed:23359680, ECO:0000269|PubMed:28007905}. 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 SPG79; decreased protein abundance.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  216
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  223
The length of the canonical sequence.

Location on the sequence:   DAAKVCREFTEREQGEVRFS  A VALCKAA
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.

Human                         DAAKVCREFTEREQGEVRFSAVALCKAA

Mouse                         DAAKVCREFTEREQGEVRFSAVALCKAA

Rat                           DAAKVCREFTEREQGEVRFSAVALCKAA

Pig                           DAAKVCREFTEREQGEVRFSAVALCKAA

Bovine                        DAAKVCREFTEREQGEVRFSAVALCKAA

Horse                         DAAKVCREFTEREQGEVRFSAVALCKAA

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.

TypePositionsDescription
Chain 1 – 220 Ubiquitin carboxyl-terminal hydrolase isozyme L1
Region 211 – 216 Interaction with ubiquitin
Site 220 – 220 Susceptible to oxidation
Lipidation 220 – 220 S-farnesyl cysteine
Mutagenesis 204 – 204 F -> A. Almost complete loss of activity.
Beta strand 215 – 221


Literature citations

Novel UCHL1 mutations reveal new insights into ubiquitin processing.
Rydning S.L.; Backe P.H.; Sousa M.M.; Iqbal Z.; Oeye A.M.; Sheng Y.; Yang M.; Lin X.; Slupphaug G.; Nordenmark T.H.; Vigeland M.D.; Bjoeraas M.; Tallaksen C.M.; Selmer K.K.;
Hum. Mol. Genet. 26:1031-1040(2017)
Cited for: VARIANTS SPG79 GLN-178 AND ASP-216; CHARACTERIZATION OF VARIANTS SPG79 GLN-178 AND ASP-216;

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.