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UniProtKB/Swiss-Prot P08473: Variant p.Ala422Asp

Neprilysin
Gene: MME
Variant information

Variant position:  422
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 Alanine (A) to Aspartate (D) at position 422 (A422D, p.Ala422Asp).
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 hydrophobic (A) to medium size and acidic (D)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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:  In CMT2T; late-onset form; results in reduction of neprilysin activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  422
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  750
The length of the canonical sequence.

Location on the sequence:   TSETATWRRCANYVNGNMEN  A VGRLYVEAAFAGESKHVVED
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                         TSETATWRRCANYVNGNMENAVGRLYVEAAFAGESKHVVED

Mouse                         TSETATWRRCANYVNGNMENAVGRLYVEAAFAGESKHVVED

Rat                           TSETATWRRCANYVNGNMENAVGRLYVEAAFAGESKHVVED

Rabbit                        TSESATWRRCANYVNGNMENAVGRLYVEAAFAGESKHVVED

Drosophila                    QSERTRWSQCVEWTNKKLGVAVGALFIRDNFNQESKEVALE

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 2 – 750 Neprilysin
Topological domain 52 – 750 Extracellular
Domain 56 – 750 Peptidase M13
Disulfide bond 80 – 735
Disulfide bond 88 – 695
Helix 420 – 431


Literature citations

Rare variants in MME, encoding metalloprotease neprilysin, are linked to late-onset autosomal-dominant axonal polyneuropathies.
Auer-Grumbach M.; Toegel S.; Schabhuettl M.; Weinmann D.; Chiari C.; Bennett D.L.; Beetz C.; Klein D.; Andersen P.M.; Boehme I.; Fink-Puches R.; Gonzalez M.; Harms M.B.; Motley W.; Reilly M.M.; Renner W.; Rudnik-Schoeneborn S.; Schlotter-Weigel B.; Themistocleous A.C.; Weishaupt J.H.; Ludolph A.C.; Wieland T.; Tao F.; Abreu L.; Windhager R.; Zitzelsberger M.; Strom T.M.; Walther T.; Scherer S.S.; Zuechner S.; Martini R.; Senderek J.;
Am. J. Hum. Genet. 99:607-623(2016)
Cited for: FUNCTION; CATALYTIC ACTIVITY; INVOLVEMENT IN CMT2T; VARIANTS CMT2T ALA-12; CYS-347; PRO-348 AND ASP-422; CHARACTERIZATION OF VARIANTS CMT2T CYS-347 AND ASP-422;

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.