UniProtKB/Swiss-Prot O14773: Variant p.Trp548Arg

Tripeptidyl-peptidase 1
Gene: TPP1
Chromosomal location: 11p15
Variant information

Variant position:  548
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Tryptophan (W) to Arginine (R) at position 548 (W548R, p.Trp548Arg).
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 large size and aromatic (W) to large size and basic (R)
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

Involvement in disease:  Ceroid lipofuscinosis, neuronal, 2 (CLN2) [MIM:204500]: A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment pattern seen most often in CLN2 consists of curvilinear profiles. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In CLN2.
Any additional useful information about the variant.



Sequence information

Variant position:  548
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:   DEEVEGQGFCSGPGWDPVTG  W GTPNFPALLKTLLNP
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                         DEEVEGQGFCSGPGWDPVTGWGTPNFPALLKTLLNP-----

Chimpanzee                    DEEVEGQGFCSGPGWDPVTGWGTPNFPALLKTLLNP

Mouse                         NEEVEGQGFCSGPGWDPVTGWGTPNFPALLKTLLNP

Rat                           NEEVEGQGFCSGPGWDPVTGWGTPNFPALLKTLLNP

Bovine                        NEEVEGQGFCSGPGWDPVTGWGTPNFPALLKTLMNP

Dog                           NEEVQGQGFCSGPGWDPVTGWGTPNFPALLKALIKP

Slime mold                    N------GFKSKSGWDPVTGLGLPNFDELVKYCLE-

Baker's yeast                 ------------------------------------

Fission yeast                 NKETSFAVTIGSDKKLSIADWCIADPANVIDILADL

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
Metal binding 539 – 539 Calcium; via carbonyl oxygen
Metal binding 541 – 541 Calcium; via carbonyl oxygen
Metal binding 543 – 543 Calcium


Literature citations

Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses.
Kousi M.; Lehesjoki A.E.; Mole S.E.;
Hum. Mutat. 33:42-63(2012)
Cited for: VARIANTS CLN2 THR-62; HIS-209; GLN-266; GLN-339; ARG-382; VAL-448; CYS-501; TYR-504 AND ARG-548;

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.