Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P57727: Variant p.Cys194Phe

Transmembrane protease serine 3
Gene: TMPRSS3
Feedback?
Variant information Variant position: help 194 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 Cysteine (C) to Phenylalanine (F) at position 194 (C194F, p.Cys194Phe). 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 medium size and polar (C) to large size and aromatic (F) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 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 DFNB8; fails to undergo proteolytic cleavage and is unable to activate ENaC. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 194 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 454 The length of the canonical sequence.
Location on the sequence: help HLLPDDKVTALHHSVYVREG C ASGHVVTLQCTACGHRRGYS 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                         HLLPDDKVTALHHSVYVREGCASGHVVTLQCTACGHRRGYS

Mouse                         HLLSDDKVTALHHSVYMREGCTSGHVVTLKCSACGTRTGYS
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 1 – 454 Transmembrane protease serine 3
Topological domain 70 – 454 Extracellular
Domain 109 – 205 SRCR
Disulfide bond 129 – 194
Disulfide bond 142 – 204



Literature citations
The transmembrane serine protease (TMPRSS3) mutated in deafness DFNB8/10 activates the epithelial sodium channel (ENaC) in vitro.
Guipponi M.; Vuagniaux G.; Wattenhofer M.; Shibuya K.; Vazquez M.; Dougherty L.; Scamuffa N.; Guida E.; Okui M.; Rossier C.; Hancock M.; Buchet K.; Reymond A.; Hummler E.; Marzella P.L.; Kudoh J.; Shimizu N.; Scott H.S.; Antonarakis S.E.; Rossier B.C.;
Hum. Mol. Genet. 11:2829-2836(2002)
Cited for: SUBCELLULAR LOCATION; AUTOCATALYTIC CLEAVAGE; MUTAGENESIS OF SER-401; CHARACTERIZATION OF VARIANTS DFNB8 GLY-103; TRP-109; PHE-194; CYS-251; LEU-404 AND ARG-407; FUNCTION IN ENAC CLEAVAGE; Novel mutations of TMPRSS3 in four DFNB8/B10 families segregating congenital autosomal recessive deafness.
Ben-Yosef T.; Wattenhofer M.; Riazuddin S.; Ahmed Z.M.; Scott H.S.; Kudoh J.; Shibuya K.; Antonarakis S.E.; Bonne-Tamir B.; Radhakrishna U.; Naz S.; Ahmed Z.; Riazuddin S.; Pandya A.; Nance W.E.; Wilcox E.R.; Friedman T.B.; Morell R.J.;
J. Med. Genet. 38:396-400(2001)
Cited for: VARIANTS DFNB8 TRP-109; PHE-194 AND ARG-407; VARIANTS ILE-53; SER-111 AND VAL-253;
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.