Sequence information
Variant position: 828 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 860 The length of the canonical sequence.
Location on the sequence: 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: The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human LLWKNWRLKNINSINFDNPVY QKTTEDEVHICHNQDGYSYP
Mouse LLWRNWRLKNINSINFDNPVY QKTTEDELHICRSQDGYTYP
Rat LLWRNWRLRNINSINFDNPVY QKTTEDEIHICRSQDGYTYP
Bovine LLWKNWRLKSINSINFDNPVY QKTTEDEVHICRSQDGYTYP
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.
Type Positions Description
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 FH 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 FH 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.