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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9NUN7: Variant p.Glu33Gly

Alkaline ceramidase 3
Gene: ACER3
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Variant information Variant position: help 33 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 Glutamate (E) to Glycine (G) at position 33 (E33G, p.Glu33Gly). 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 medium size and acidic (E) to glycine (G) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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

Variant description: help In PLDECO; impaired protein stability; strongly decreased enzyme activity; decreased ceramide catabolic process; in fibroblasts of patients homozygous for the mutation. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 33 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 267 The length of the canonical sequence.
Location on the sequence: help PTTSTLDWCEENYSVTWYIA E FWNTVSNLIMIIPPMFGAVQ 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                         PTTSTLDWCEENYSVTWYIAEFWNTVSNLIMIIPPMFGAVQ

Mouse                         PTTSTLDWCEENYVVTLFVAEFWNTVSNLIMIIPPIFGAIQ

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 1 – 267 Alkaline ceramidase 3
Topological domain 1 – 33 Cytoplasmic
Binding site 19 – 19
Binding site 20 – 20
Binding site 22 – 22
Binding site 24 – 24
Binding site 33 – 33
Alternative sequence 1 – 133 Missing. In isoform 2.
Mutagenesis 19 – 19 D -> G. Mildly decreased enzyme activity.
Mutagenesis 22 – 22 E -> G. Strongly decreased enzyme activity.
Mutagenesis 24 – 24 N -> G. Strongly decreased enzyme activity.
Beta strand 32 – 34



Literature citations
Deficiency of the alkaline ceramidase ACER3 manifests in early childhood by progressive leukodystrophy.
Edvardson S.; Yi J.K.; Jalas C.; Xu R.; Webb B.D.; Snider J.; Fedick A.; Kleinman E.; Treff N.R.; Mao C.; Elpeleg O.;
J. Med. Genet. 53:389-396(2016)
Cited for: FUNCTION; CATALYTIC ACTIVITY; INVOLVEMENT IN PLDECO; VARIANT PLDECO GLY-33; CHARACTERIZATION OF VARIANT PLDECO GLY-33; Structure of a human intramembrane ceramidase explains enzymatic dysfunction found in leukodystrophy.
Vasiliauskaite-Brooks I.; Healey R.D.; Rochaix P.; Saint-Paul J.; Sounier R.; Grison C.; Waltrich-Augusto T.; Fortier M.; Hoh F.; Saied E.M.; Arenz C.; Basu S.; Leyrat C.; Granier S.;
Nat. Commun. 9:5437-5437(2018)
Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 2-244 IN COMPLEX WITH CALCIUM AND ZINC IONS; FUNCTION; CATALYTIC ACTIVITY; COFACTOR; PATHWAY; CHARACTERIZATION OF VARIANT PLDECO GLY-33; SUBCELLULAR LOCATION; TOPOLOGY; MUTAGENESIS OF ASP-19; GLU-22; ASN-24; SER-99; TYR-149 AND SER-228;
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.