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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q06136: Variant p.Tyr186Phe

3-ketodihydrosphingosine reductase
Gene: KDSR
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Variant information Variant position: help 186 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 Tyrosine (Y) to Phenylalanine (F) at position 186 (Y186F, p.Tyr186Phe). 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 large size and aromatic. 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 EKVP4; impairs enzyme activity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 186 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 332 The length of the canonical sequence.
Location on the sequence: help GRIVFVSSQAGQLGLFGFTA Y SASKFAIRGLAEALQMEVKP 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                         GRIVFVSSQAGQLGLFGFTAYSASKFAIRGLAEALQMEVKP

Mouse                         GRIVFVSSQAGQLGLFGFTAYSSSKFAIRGLAEALQMEVKP

Bovine                        GRVVFVSSQAGQLGLFGYTAYSSSKFALRGLAEALQMEVKP

Zebrafish                     GRIMFVSSQAGQIGLFGYTAYSPSKFALRGLAEALQMEMKP

Slime mold                    GHIVFVSSTCGLVGVPGYSTYCPSKFALRGLAETLRSELKP

Baker's yeast                 HHLIIFSSATALYPFVGYSQYAPAKAAIKSLVAILRQELTN
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 26 – 332 3-ketodihydrosphingosine reductase
Topological domain 26 – 270 Cytoplasmic
Active site 172 – 172 Proton donor
Active site 186 – 186 Proton acceptor
Active site 190 – 190 Lowers pKa of active site Tyr
Binding site 186 – 186
Binding site 190 – 190
Alternative sequence 139 – 202 Missing. In isoform 2.
Mutagenesis 173 – 173 S -> A. Impairs activity.
Mutagenesis 175 – 175 A -> TV. Impairs activity.
Mutagenesis 186 – 186 Y -> Q. Impairs activity.
Mutagenesis 190 – 190 K -> RI. Impairs activity.



Literature citations
Mutations in KDSR cause recessive progressive symmetric erythrokeratoderma.
Boyden L.M.; Vincent N.G.; Zhou J.; Hu R.; Craiglow B.G.; Bayliss S.J.; Rosman I.S.; Lucky A.W.; Diaz L.A.; Goldsmith L.A.; Paller A.S.; Lifton R.P.; Baserga S.J.; Choate K.A.;
Am. J. Hum. Genet. 100:978-984(2017)
Cited for: VARIANTS EKVP4 55-GLN-GLY-56 DELINS ARG; 86-VAL--GLN-107 DEL; PHE-186 AND 260-GLN--GLN-293 DEL; CHARACTERIZATION OF VARIANTS EKVP4 55-GLN-GLY-56 DELINS ARG; 86-VAL--GLN-107 DEL AND 260-GLN--GLN-293 DEL; FUNCTION; Tsc10p and FVT1: topologically distinct short-chain reductases required for long-chain base synthesis in yeast and mammals.
Gupta S.D.; Gable K.; Han G.; Borovitskaya A.; Selby L.; Dunn T.M.; Harmon J.M.;
J. Lipid Res. 50:1630-1640(2009)
Cited for: CHARACTERIZATION OF VARIANT EKVP4 PHE-186; FUNCTION; CATALYTIC ACTIVITY; SUBUNIT; SUBCELLULAR LOCATION; TOPOLOGY; MUTAGENESIS OF SER-173; ALA-175; TYR-186 AND LYS-190;
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.