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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P02649: Variant p.Arg154Ser

Apolipoprotein E
Gene: APOE
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Variant information Variant position: help 154 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 Arginine (R) to Serine (S) at position 154 (R154S, p.Arg154Ser). 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 large size and basic (R) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In HLPP3; ApoE2 Christchurch; decreased binding to LDL receptor. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 154 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 317 The length of the canonical sequence.
Location on the sequence: help VQYRGEVQAMLGQSTEELRV R LASHLRKLRKRLLRDADDLQ 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                         VQYRGEVQAMLGQSTEELRVRLASHLRKLRKRLLRDADDLQ

Gorilla                       AQYRGEVQAMLGQSTEELRARLASHLRKLRKRLLRDADDLQ

                              TQYRGELQAMLGQSSEELRARFASHMRKLRKRVLRDAEDLQ

Rhesus macaque                VQYRSEVQAMLGQSTEELRARLASHLRKLRKRLLRDADDLQ

Chimpanzee                    VQYRGEVQAMLGQSTEELRARLASHLRKLRKRLLRDADDLQ

Mouse                         GQYRNEVHTMLGQSTEEIRARLSTHLRKMRKRLMRDAEDLQ

Rat                           GQYRNEVNTMLGQSTEELRSRLSTHLRKMRKRLMRDADDLQ

Pig                           VLYRSEVHNMLGQTTEELRSRLASHLRNVRKRLVRDTEDLQ

Bovine                        AQYRSEVQAMLGQSTEELRARMASHLRKLPKRLLRDADDLK

Rabbit                        AQYRGEAQAMLGQSTEELARAFSSHLRKLRKRLLRDAEDLQ

Sheep                         AQYRSEVQAMLGQSTEELRARMASHLRKLRKRLLRDADDLK
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 19 – 317 Apolipoprotein E
Repeat 146 – 167 4
Region 80 – 255 8 X 22 AA approximate tandem repeats
Modified residue 143 – 143 Methionine sulfoxide
Modified residue 147 – 147 Phosphoserine; by FAM20C
Mutagenesis 157 – 157 S -> R. Increased binding to LDL receptor; when associated with A-167.
Mutagenesis 158 – 158 H -> A. Decreased binding to LDL receptor.
Mutagenesis 161 – 161 K -> A. Decreased binding to LDL receptor.
Mutagenesis 162 – 162 L -> P. Decreased binding to LDL receptor.
Mutagenesis 167 – 167 L -> A. Increased binding to LDL receptor; when associated with R-157.
Mutagenesis 168 – 168 R -> A. Decreased binding to LDL receptor.
Mutagenesis 172 – 172 D -> A. Restores the LDL receptor binding activity of ApoE2.
Helix 149 – 180



Literature citations
Site-specific mutagenesis of human apolipoprotein E. Receptor binding activity of variants with single amino acid substitutions.
Lalazar A.; Weisgraber K.H.; Rall S.C. Jr.; Giladi H.; Innerarity T.L.; Levanon A.Z.; Boyles J.K.; Amit B.; Gorecki M.; Mahley R.W.;
J. Biol. Chem. 263:3542-3545(1988)
Cited for: CHARACTERIZATION OF VARIANTS SER-154 AND PRO-170; MUTAGENESIS OF SER-157; HIS-158; LYS-161; LEU-162; LEU-167 AND ARG-168; Common and rare genotypes of human apolipoprotein E determined by specific restriction profiles of polymerase chain reaction-amplified DNA.
Richard P.; Thomas G.; de Zulueta M.P.; de Gennes J.-L.; Thomas M.; Cassaigne A.; Bereziat G.; Iron A.;
Clin. Chem. 40:24-29(1994)
Cited for: VARIANTS HLPP3 ARG-130; SER-154; CYS-160 AND CYS-176; VARIANT ASP-145; Apolipoprotein E gene mutations in subjects with mixed hyperlipidemia and a clinical diagnosis of familial combined hyperlipidemia.
Solanas-Barca M.; de Castro-Oros I.; Mateo-Gallego R.; Cofan M.; Plana N.; Puzo J.; Burillo E.; Martin-Fuentes P.; Ros E.; Masana L.; Pocovi M.; Civeira F.; Cenarro A.;
Atherosclerosis 222:449-455(2012)
Cited for: VARIANT HLPP3 SER-154; VARIANT SBHD LEU-167 DEL;
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.