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UniProtKB/Swiss-Prot P02649: Variant p.Arg163Pro

Apolipoprotein E
Gene: APOE
Chromosomal location: 19q13.2
Variant information

Variant position:  163
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 Arginine (R) to Proline (P) at position 163 (R163P, p.Arg163Pro).
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 large size and basic (R) to medium size and hydrophobic (P)
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:  Lipoprotein glomerulopathy (LPG) [MIM:611771]: Uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries. {ECO:0000269|PubMed:10432380, ECO:0000269|PubMed:10903326, ECO:0000269|PubMed:18077821, ECO:0000269|PubMed:9176854}. 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 LPG; ApoE2 Sendai; decreased binding to LDL receptor; induces intraglomerular deposition of ApoE-containing lipoproteins.
Any additional useful information about the variant.

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

Sequence information

Variant position:  163
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  317
The length of the canonical sequence.

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.











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.

Chain 19 – 317 Apolipoprotein E
Repeat 146 – 167 4
Region 80 – 255 8 X 22 AA approximate tandem repeats
Region 158 – 168 LDL and other lipoprotein receptors binding
Region 162 – 165 Heparin-binding
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 – 179

Literature citations

Apolipoprotein E Sendai (arginine 145-->proline): a new variant associated with lipoprotein glomerulopathy.
Oikawa S.; Matsunaga A.; Saito T.; Sato H.; Seki T.; Hoshi K.; Hayasaka K.; Kotake H.; Midorikawa H.; Sekikawa A.; Hara S.; Abe K.; Toyota T.; Jingami H.; Nakamura H.; Sasaki J.;
J. Am. Soc. Nephrol. 8:820-823(1997)
Cited for: VARIANT LPG PRO-163;

Virus-mediated transduction of apolipoprotein E (ApoE)-sendai develops lipoprotein glomerulopathy in ApoE-deficient mice.
Ishigaki Y.; Oikawa S.; Suzuki T.; Usui S.; Magoori K.; Kim D.H.; Suzuki H.; Sasaki J.; Sasano H.; Okazaki M.; Toyota T.; Saito T.; Yamamoto T.T.;
J. Biol. Chem. 275:31269-31273(2000)

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.