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UniProtKB/Swiss-Prot P07204: Variant p.Asp486Tyr

Thrombomodulin
Gene: THBD
Variant information

Variant position:  486
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 Aspartate (D) to Tyrosine (Y) at position 486 (D486Y, p.Asp486Tyr).
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 acidic (D) to large size and aromatic (Y)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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 THPH12 and 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.



Sequence information

Variant position:  486
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:   CGPDSALARHIGTDCDSGKV  D GGDSGSGEPPPSPTPGSTLT
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                         CGPDSALARHIGTDCDSGKVD---GGDSGSGEPPPSPTPGSTLT

                              CGPDSPLAGQVATDCGRIISDPDGDSDSGSGEPPVTPTPGV

Mouse                         CGPDTALAGQISKDCDPIPVREDTKEEEGSGEPPVSPTPGS

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.

TypePositionsDescription
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

The first mutation identified in the thrombomodulin gene in a 45-year-old man presenting with thromboembolic disease.
Oehlin A.-K.; Marlar R.A.;
Blood 85:330-336(1995)
Cited for: VARIANT THPH12 TYR-486;

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;

Mutations in the thrombomodulin gene are rare in patients with severe thrombophilia.
Faioni E.M.; Franchi F.; Castaman G.; Biguzzi E.; Rodeghiero F.;
Br. J. Haematol. 118:595-599(2002)
Cited for: VARIANT THPH12 TYR-486; VARIANT VAL-473;

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;

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.