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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q5JRX3: Variant p.Arg183Gln

Presequence protease, mitochondrial
Gene: PITRM1
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Variant information Variant position: help 183 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 Glutamine (Q) at position 183 (R183Q, p.Arg183Gln). 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 medium size and polar (Q) 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 SCAR30; decreased function in degradation of amyloid-beta protein 40; decreased metalloendopeptidase activity towards different substrates including an amyloid-beta peptide derivative; decreased protein levels in patient tissues; no effect on mitochondrial localization. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 183 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1037 The length of the canonical sequence.
Location on the sequence: help YLDATFFPCLRELDFWQEGW R LEHENPSDPQTPLVFKGVVF 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                         YLDATFFPCLRELDFWQEGWRLEHENPSDPQTPLVFKGVVF

Mouse                         YLDATFFPCLRELDFWQEGWRLEHENPRDPQTPLIFKGVVF

Xenopus laevis                YLDAVFFPCLRELDFWQEGWRLEHENPEDPNSPLIFKGIVF

Xenopus tropicalis            YLDAVFFPCLRELDFWQEGWRLEHENPEDPNSPLIFKGIVF

Zebrafish                     YLDAVFFPCLRELDFWQEGWRLEHENPTDPSSPLVFKGVVF

Drosophila                    YLDAVFRPNLAYFDFLQEGWRLENKDIFDKQSKLVIKGVVY

Baker's yeast                 YLDSTLNPLLKQEDFDQEGWRLEHKNITDPESNIVFKGVVY

Fission yeast                 YLDATLFPKLRKLDFLQEGWRFEHADVNDKKSPIIFNGVVY
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 29 – 1037 Presequence protease, mitochondrial
Active site 180 – 180
Disulfide bond 119 – 556
Mutagenesis 182 – 199 Missing. Loss of metalloendopeptidase activity towards an amyloid-beta peptide derivative.
Mutagenesis 183 – 183 R -> AKN. Decreased metalloendopeptidase activity towards an amyloid-beta peptide derivative.
Mutagenesis 183 – 183 R -> DE. Loss of metalloendopeptidase activity towards an amyloid-beta peptide derivative.
Mutagenesis 185 – 185 E -> A. Loss of metalloendopeptidase activity towards an amyloid-beta peptide derivative.
Mutagenesis 185 – 185 E -> DQ. No effect on metalloendopeptidase activity towards an amyloid-beta peptide derivative.
Mutagenesis 185 – 185 E -> RKN. Decreased metalloendopeptidase activity towards an amyloid-beta peptide derivative.
Mutagenesis 199 – 199 K -> ADEQ. Decreased metalloendopeptidase activity towards an amyloid-beta peptide derivative.
Mutagenesis 199 – 199 K -> NR. No effect on metalloendopeptidase activity towards an amyloid-beta peptide derivative.
Beta strand 183 – 188



Literature citations
Defective PITRM1 mitochondrial peptidase is associated with Abeta amyloidotic neurodegeneration.
Brunetti D.; Torsvik J.; Dallabona C.; Teixeira P.; Sztromwasser P.; Fernandez-Vizarra E.; Cerutti R.; Reyes A.; Preziuso C.; D'Amati G.; Baruffini E.; Goffrini P.; Viscomi C.; Ferrero I.; Boman H.; Telstad W.; Johansson S.; Glaser E.; Knappskog P.M.; Zeviani M.; Bindoff L.A.;
EMBO Mol. Med. 8:176-190(2016)
Cited for: VARIANT SCAR30 GLN-183; INVOLVEMENT IN SCAR30; CHARACTERIZATION OF VARIANT SCAR30 GLN-183; FUNCTION; SUBCELLULAR LOCATION;
Functional requirement for human pitrilysin metallopeptidase 1 arginine 183, mutated in amyloidogenic neuropathy.
Smith-Carpenter J.E.; Alper B.J.;
Protein Sci. 27:861-873(2018)
Cited for: VARIANT SCAR30 GLN-183; CHARACTERIZATION OF VARIANT SCAR30 GLN-183; MUTAGENESIS OF GLU-107; 182-TRP--LYS-199; ARG-183; GLU-185 AND LYS-199; FUNCTION;
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.