UniProtKB/Swiss-Prot P07225: Variant p.Ser501Pro

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 501 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LB/B 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: From Serine (S) to Proline (P) at position 501 (S501P, p.Ser501Pro). 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 small size and polar (S) to medium size and hydrophobic (P) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: -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: Variant Heerlen. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs121918472 [ dbSNP | Ensembl ]

Sequence information

Variant position: 501 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 676 The length of the canonical sequence.
Location on the sequence: KGSYYPGSGIAQFHIDYNNV S SAEGWHVNVTLNIRPSTGTG 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.
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	42 – 676	Vitamin K-dependent protein S
Domain	484 – 666	Laminin G-like 2
Site	499 – 499	Not glycosylated; in variant Heerlen
Glycosylation	499 – 499	N-linked (GlcNAc...) asparagine
Glycosylation	509 – 509	N-linked (GlcNAc...) asparagine
Mutagenesis	515 – 515	R -> AE. Markedly reduced secretion of the mutant.
Mutagenesis	515 – 515	R -> K. No change in secretion of the mutant.

Literature citations

Heerlen polymorphism of protein S, an immunologic polymorphism due to dimorphism of residue 460.
Bertina R.M.; Ploos van Amstel H.K.; van Wijngaarden A.; Coenen J.; Leemhuis M.P.; Deutz-Terlouw P.P.; van der Linden I.K.; Reitsma P.H.;
Blood 76:538-548(1990)
Cited for: VARIANT PRO-501; Identification of 19 protein S gene mutations in patients with phenotypic protein S deficiency and thrombosis.
Simmonds R.E.; Ireland H.; Kunz G.; Lane D.A.;
Blood 88:4195-4204(1996)
Cited for: VARIANTS THPH5 GLU-50; ALA-67; GLU-95; TYR-186; SER-241; PRO-324; ASP-381; SER-449 AND ARG-666; VARIANT PRO-501; Molecular basis for protein S hereditary deficiency: genetic defects observed in 118 patients with type I and type IIa deficiencies.
Borgel D.; Duchemin J.; Alhenc-Gelas M.; Matheron C.; Aiach M.; Gandrille S.;
J. Lab. Clin. Med. 128:218-227(1996)
Cited for: VARIANTS THPH5 SER-111; GLY-157; GLY-161; GLU-364; PRO-446; ARG-475; ALA-501; MET-508; CYS-515; PRO-525; ALA-532; TYR-568; ARG-575 AND ARG-666; VARIANT PRO-501; Protein S gene analysis reveals the presence of a cosegregating mutation in most pedigrees with type I but not type III PS deficiency.
Espinosa-Parrilla Y.; Morell M.; Souto J.C.; Tirado I.; Fontcuberta J.; Estivill X.; Sala N.;
Hum. Mutat. 14:30-39(1999)
Cited for: VARIANTS THPH5 CYS-482; CYS-485 AND GLY-561; VARIANTS PRO-501 AND MET-559; Molecular diversity and thrombotic risk in protein S deficiency: the PROSIT study.
Biguzzi E.; Razzari C.; Lane D.A.; Castaman G.; Cappellari A.; Bucciarelli P.; Fontana G.; Margaglione M.; D'Andrea G.; Simmonds R.E.; Rezende S.M.; Preston R.; Prisco D.; Faioni E.M.;
Hum. Mutat. 25:259-269(2005)
Cited for: VARIANTS THPH5 ALA-67; TYR-88; GLY-129; ASN-144; PHE-175; GLY-204; CYS-266; SER-267; ASP-336; ARG-357; PRO-446; PRO-515; ASP-521; LYS-611; ASP-638 AND TYR-639; VARIANTS LEU-76; PRO-501; MET-559; LEU-562 AND HIS-583; CHARACTERIZATION OF VARIANTS PROS1 DEFICIENCY ALA-67; TYR-88; GLY-129; PHE-175; GLY-204; CYS-266; SER-267; ASP-336; ARG-357; PRO-446; PRO-515; ASP-521; LYS-611; ASP-638 AND TYR-639; CHARACTERIZATION OF VARIANTS LEU-76; LEU-562 AND HIS-583;