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UniProtKB/Swiss-Prot O14773: Variant p.Asn286Ser

Tripeptidyl-peptidase 1
Gene: TPP1
Variant information

Variant position:  286
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 Asparagine (N) to Serine (S) at position 286 (N286S, p.Asn286Ser).
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 polar (N) 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 CLN2; enzymatically inactive; lacks one oligosaccharide chain resulting in enzymatic inactivation and possibly prelysosomal protein degradation; altered intracellular trafficking.
Any additional useful information about the variant.

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



Sequence information

Variant position:  286
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  563
The length of the canonical sequence.

Location on the sequence:   RGRAGIEASLDVQYLMSAGA  N ISTWVYSSPGRHEGQEPFLQ
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                         RGRAGIEASLDVQYLMSAGANISTW-----VYSSPGRHEGQEPFLQ

                              RGRAGIEASLDVEYLMSAGANISTW-----VYSSPGRHESQ

Chimpanzee                    RGRAGIEASLDVQYLMSAGANISTW-----VYSSPGRHEGQ

Mouse                         RGRAGIEASLDVEYLMSAGANISTW-----VYSSPGRHEAQ

Rat                           RGRAGIEASLDVEYLMSAGANISTW-----VYSSPGRHEAQ

Bovine                        RGRAGIEASLDVEYLMSAGANISTW-----VYSSPGRHESQ

Zebrafish                     GGKAGIEASLDVEYIMSSGANISTW-----VFTNPGRHESQ

Slime mold                    NLNPGIETALDIQYIMAMAPDVPTW-----IVSTGGLHEGQ

Baker's yeast                 RGET---------------LSHRLW-----LYAAPKRP---

Fission yeast                 FGTDDYTPVHHVEEQLEPADYFALLTRADALFINSIREGVS

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 196 – 563 Tripeptidyl-peptidase 1
Domain 199 – 563 Peptidase S53
Active site 272 – 272 Charge relay system
Active site 276 – 276 Charge relay system
Glycosylation 286 – 286 N-linked (GlcNAc...) asparagine
Turn 284 – 286


Literature citations

Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations.
Steinfeld R.; Heim P.; von Gregory H.; Meyer K.; Ullrich K.; Goebel H.H.; Kohlschutter A.;
Am. J. Med. Genet. 112:347-354(2002)
Cited for: VARIANTS CLN2 GLN-127; SER-286 AND PRO-353;

Mutation of the glycosylated asparagine residue 286 in human CLN2 protein results in loss of enzymatic activity.
Tsiakas K.; Steinfeld R.; Storch S.; Ezaki J.; Lukacs Z.; Kominami E.; Kohlschuetter A.; Ullrich K.; Braulke T.;
Glycobiology 14:1C-5C(2004)
Cited for: CHARACTERIZATION OF VARIANT CLN2 SER-286;

Functional consequences and rescue potential of pathogenic missense mutations in tripeptidyl peptidase I.
Walus M.; Kida E.; Golabek A.A.;
Hum. Mutat. 31:710-721(2010)
Cited for: VARIANT CLN2 SER-544; CHARACTERIZATION OF VARIANTS CLN2 ARG-77; GLN-127; LEU-202; CYS-206; MET-277; VAL-284; SER-286; ASN-287; LYS-343; ARG-365; HIS-422; HIS-447; LEU-475 AND SER-544;

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.