UniProtKB/Swiss-Prot P45381: Variant p.Glu285Ala

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 285 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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: From Glutamate (E) to Alanine (A) at position 285 (E285A, p.Glu285Ala). 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 medium size and acidic (E) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: -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: In CAND; predominant mutation in Ashkenazi Jewish population; 99% loss of activity. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs28940279 [ dbSNP | Ensembl ]

Sequence information

Variant position: 285 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 313 The length of the canonical sequence.
Location on the sequence: LDGKTIPLGGDCTVYPVFVN E AAYYEKKEAFAKTTKLTLNA 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.
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.

Type	Positions	Description
Chain	1 – 313	Aspartoacylase
Binding site	288 – 288
Mutagenesis	285 – 285	E -> D. 5-fold decrease in activity.
Mutagenesis	288 – 288	Y -> F. Reduces activity by 99%.

Literature citations

Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease.
Kaul R.; Gao G.P.; Balamurugan K.; Matalon R.;
Nat. Genet. 5:118-123(1993)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; FUNCTION; CATALYTIC ACTIVITY; TISSUE SPECIFICITY; VARIANT CAND ALA-285; Purification and preliminary characterization of brain aspartoacylase.
Moore R.A.; Le Coq J.; Faehnle C.R.; Viola R.E.;
Arch. Biochem. Biophys. 413:1-8(2003)
Cited for: CATALYTIC ACTIVITY; CHARACTERIZATION; CHARACTERIZATION OF VARIANT CAND ALA-285; MUTAGENESIS OF GLU-285; Canavan disease: mutations among Jewish and non-Jewish patients.
Kaul R.; Gao G.P.; Aloya M.; Balamurugan K.; Petrosky A.; Michals K.; Matalon R.;
Am. J. Hum. Genet. 55:34-41(1994)
Cited for: VARIANTS CAND ALA-285 AND GLU-305; Identification and expression of eight novel mutations among non-Jewish patients with Canavan disease.
Kaul R.; Gao G.P.; Matalon R.; Aloya M.; Su Q.; Jin M.; Johnson A.B.; Schutgens R.B.H.; Clarke J.T.R.;
Am. J. Hum. Genet. 59:95-102(1996)
Cited for: VARIANTS CAND THR-16; ARG-27; GLU-114; GLU-123; TYR-152; CYS-168; ALA-285 AND GLU-305; VARIANT GLY-310; CHARACTERIZATION OF VARIANTS CAND THR-16; ARG-27; GLU-114; GLU-123; TYR-152 AND CYS-168; Clinically distinct phenotypes of Canavan disease correlate with residual aspartoacylase enzyme activity.
Mendes M.I.; Smith D.E.; Pop A.; Lennertz P.; Fernandez Ojeda M.R.; Kanhai W.A.; van Dooren S.J.; Anikster Y.; Baric I.; Boelen C.; Campistol J.; de Boer L.; Kariminejad A.; Kayserili H.; Roubertie A.; Verbruggen K.T.; Vianey-Saban C.; Williams M.; Salomons G.S.;
Hum. Mutat. 38:524-531(2017)
Cited for: VARIANTS CAND LYS-24; PRO-30; VAL-57; THR-63; ARG-69; VAL-101; LYS-129; THR-170; VAL-180; HIS-204; ARG-248 AND ASP-286; CHARACTERIZATION OF VARIANTS CAND LYS-24; PRO-30; VAL-57; THR-63; ARG-69; VAL-101; LYS-129; THR-170; VAL-180; HIS-204; ARG-248; ALA-285 AND ASP-286; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES;