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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q8NBP7: Variant p.Arg218Ser

Proprotein convertase subtilisin/kexin type 9
Gene: PCSK9
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Variant information Variant position: help 218 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 218 (R218S, p.Arg218Ser). 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 FHCL3; complete loss of cleavage by furin and PCSK5; reduces glycosylation levels; no effect on protein sulfation and phosphorylation; no effect on protein sulfation but inhibits phosphorylation when associated with Y-374; highly reduces LDL uptake when associated with Y-374. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 218 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 692 The length of the canonical sequence.
Location on the sequence: help GRVMVTDFENVPEEDGTRFH R QASKCDSHGTHLAGVVSGRD 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                         GRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRD

Gorilla                       GRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRD

Rhesus macaque                GRVMVTDFESVPEEDGTRFHRQASKCDSHGTHLAGVVSGRD

Chimpanzee                    GRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRD

Mouse                         GRVTITDFNSVPEEDGTRFHRQASKCDSHGTHLAGVVSGRD

Rat                           GRVTITDFNSVPEEDGTRFHRQASKCDSHGTHLAGVVSGRD
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 153 – 692 Proprotein convertase subtilisin/kexin type 9
Domain 155 – 461 Peptidase S8
Active site 226 – 226 Charge relay system
Site 218 – 219 Cleavage; by furin and PCSK5
Mutagenesis 226 – 226 H -> A. Remains in the endoplasmic reticulum and is not secreted.
Turn 218 – 220



Literature citations
Annexin A2 reduces PCSK9 protein levels via a translational mechanism and interacts with the M1 and M2 domains of PCSK9.
Ly K.; Saavedra Y.G.; Canuel M.; Routhier S.; Desjardins R.; Hamelin J.; Mayne J.; Lazure C.; Seidah N.G.; Day R.;
J. Biol. Chem. 289:17732-17746(2014)
Cited for: FUNCTION; INTERACTION WITH ANXA2; VARIANT GLN-482; CHARACTERIZATION OF VARIANT GLN-482; VARIANTS FHCL3 SER-218 AND TYR-374; CHARACTERIZATION OF VARIANTS FHCL3 SER-218 AND TYR-374; SULFATION; PHOSPHORYLATION; GLYCOSYLATION; SUBUNIT;
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.