UniProtKB/SwissProt variant VAR

Variant information

Variant position:

495

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

Type of variant:

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:

From Proline (P) to Serine (S) at position 495 (P495S, p.Pro495Ser).

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 medium size and hydrophobic (P) to small size and polar (S)

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:

In AHUS6; cells transfected with the mutant are less effective in converting C3b to iC3b on the cell surface after complement activation.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1800578 [ dbSNP | Ensembl ]

Sequence information

Variant position:

495

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

Protein sequence length:

575

The length of the canonical sequence.

Location on the sequence:

HIGTDCDSGKVDGGDSGSGE P PPSPTPGSTLTPPAVGLVHS

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                         HIGTDCDSGKVD---GGDSGSGEPPPSPTPGSTLTPPAVGLVHS

                              QVATDCGRIISDPDGDSDSGSGEPPVTPTPGVTPSPSPVGP

Mouse                         QISKDCDPIPVREDTKEEEGSGEPPVSPTPGSPTGPPSARP

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	19 – 575	Thrombomodulin
Topological domain	19 – 515	Extracellular
Region	481 – 515	Involved in alpha-L/beta-2 and alpha-M/beta-2 integrin binding
Region	484 – 506	Disordered
Glycosylation	490 – 490	O-linked (Xyl...) (chondroitin sulfate) serine
Glycosylation	492 – 492	O-linked (Xyl...) (chondroitin sulfate) serine

Literature citations

Thrombomodulin gene variations and thromboembolic disease.
Oehlin A.-K.; Norlund L.; Marlar R.A.;
Thromb. Haemost. 78:396-400(1997)
Cited for: VARIANT THPH12 TYR-486; VARIANTS THR-43; ALA-79; SER-495 AND LEU-501;

Thrombomodulin mutations in atypical hemolytic-uremic syndrome.
Delvaeye M.; Noris M.; De Vriese A.; Esmon C.T.; Esmon N.L.; Ferrell G.; Del-Favero J.; Plaisance S.; Claes B.; Lambrechts D.; Zoja C.; Remuzzi G.; Conway E.M.;
N. Engl. J. Med. 361:345-357(2009)
Cited for: VARIANTS AHUS6 THR-43; GLY-53; LEU-81; TYR-486; SER-495 AND LEU-501; CHARACTERIZATION OF VARIANTS AHUS6 THR-43; GLY-53; LEU-81; TYR-486; SER-495 AND LEU-501; VARIANT VAL-473;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P07204: Variant p.Pro495Ser