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UniProtKB/Swiss-Prot P01130: Variant p.Tyr828Cys

Low-density lipoprotein receptor
Gene: LDLR
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Variant information Variant position: help 828 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 Cysteine (C) at position 828 (Y828C, p.Tyr828Cys). 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 aromatic (Y) to medium size and polar (C) 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 FHCL1; J.D.Bari/Syria; 2-fold decreased affinity for LDLRAP1. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 828 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 860 The length of the canonical sequence.
Location on the sequence: help LLWKNWRLKNINSINFDNPV Y QKTTEDEVHICHNQDGYSYP 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                         LLWKNWRLKNINSINFDNPVYQKTTEDEVHICHNQDGYSYP

Mouse                         LLWRNWRLKNINSINFDNPVYQKTTEDELHICRSQDGYTYP

Rat                           LLWRNWRLRNINSINFDNPVYQKTTEDEIHICRSQDGYTYP

Bovine                        LLWKNWRLKSINSINFDNPVYQKTTEDEVHICRSQDGYTYP
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 22 – 860 Low-density lipoprotein receptor
Topological domain 811 – 860 Cytoplasmic
Region 811 – 860 Required for MYLIP-triggered down-regulation of LDLR
Motif 823 – 828 NPXY motif
Mutagenesis 811 – 811 K -> R. No change. No change; when associated with R-816 and R-830. Insensitive to MYLIP-triggered degradation; when associated with R-816; R-830 and A-839.
Mutagenesis 816 – 816 K -> R. No change. No change; when associated with R-830. No change; when associated with R-811 and R-830. Insensitive to MYLIP-triggered degradation; when associated with R-830 and A-839. Insensitive to MYLIP-triggered degradation; when associated with R-811; R-830 and A-839.
Mutagenesis 821 – 821 I -> A. 3-fold decreased affinity for LDLRAP1.
Mutagenesis 821 – 821 I -> R. 10-fold decreased affinity for LDLRAP1.
Mutagenesis 828 – 828 Y -> A. Abolishes interaction with ARRB2.
Mutagenesis 829 – 829 Q -> A. Decreased affinity for LDLRAP1.
Mutagenesis 830 – 830 K -> R. No change. No change; when associated with R-816. No change; when associated with R-811 and R-816. Insensitive to MYLIP-triggered degradation; when associated with A-839. Insensitive to MYLIP-triggered degradation; when associated with R-816 and A-839. Insensitive to MYLIP-triggered degradation; when associated with R-811; R-816 and A-839.
Mutagenesis 839 – 839 C -> A. No change. Insensitive to MYLIP-triggered degradation; when associated with R-830. Insensitive to MYLIP-triggered degradation; when associated with R-816 and R-830. Insensitive to MYLIP-triggered degradation; when associated with R-811; R-816 and R-830.
Turn 826 – 829



Literature citations
Atomic structure of the autosomal recessive hypercholesterolemia phosphotyrosine-binding domain in complex with the LDL-receptor tail.
Dvir H.; Shah M.; Girardi E.; Guo L.; Farquhar M.G.; Zajonc D.M.;
Proc. Natl. Acad. Sci. U.S.A. 109:6916-6921(2012)
Cited for: X-RAY CRYSTALLOGRAPHY (1.37 ANGSTROMS) OF 819-832 IN COMPLEX WITH LDLRAP1; INTERACTION WITH LDLRAP1; CHARACTERIZATION OF VARIANT FHCL1 CYS-828; MUTAGENESIS OF ILE-821 AND GLN-829; TOPOLOGY; MOTIF; The J.D. mutation in familial hypercholesterolemia: amino acid substitution in cytoplasmic domain impedes internalization of LDL receptors.
Davis C.G.; Lehrman M.A.; Russell D.W.; Anderson R.G.W.; Brown M.S.; Goldstein J.L.;
Cell 45:15-24(1986)
Cited for: VARIANT FHCL1 CYS-828;
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.