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UniProtKB/Swiss-Prot O14773: Variant p.Cys365Arg

Tripeptidyl-peptidase 1
Gene: TPP1
Variant information

Variant position:  365
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 Cysteine (C) to Arginine (R) at position 365 (C365R, p.Cys365Arg).
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 (C) 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

Variant description:  In CLN2; displays no residual enzyme activity; altered intracellular trafficking.
Any additional useful information about the variant.

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



Sequence information

Variant position:  365
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:   MKAAARGLTLLFASGDSGAG  C WSVSGRHQFRPTFPASSPYV
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                         MKAA-----------------ARGLTLLFASGDSGAGCWSVSGRHQ-FRPTFPASSPYV

                              MKAA-----------------ARGLTLLFASGDSGAGCWSV

Chimpanzee                    MKAA-----------------ARGLTLLFASGDSGAGCWSV

Mouse                         MKAA-----------------ARGLTLLFASGDTGAGCWSV

Rat                           MKAA-----------------ARGLTLLFASGDTGAGCWSV

Bovine                        MKAA-----------------ARGLTLLFASGDSGAGCWSV

Zebrafish                     MKAG-----------------LRGISMLFASGDSGAGCRHL

Slime mold                    KKYA-----------------AMGRTIVFSSGDFGVGC---

Baker's yeast                 VRKP-----------------MTGMVEFFKR----------

Fission yeast                 IERESYKQVTTHTMQSWTSSLIRSLANKLAATKTDQRIPTL

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
Disulfide bond 365 – 526
Mutagenesis 360 – 360 D -> A. Inactive. Impaired processing.


Literature citations

Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis.
Sleat D.E.; Donnelly R.J.; Lackland H.; Liu C.-G.; Sohar I.; Pullarkat R.K.; Lobel P.;
Science 277:1802-1805(1997)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); PARTIAL PROTEIN SEQUENCE; VARIANTS CLN2 ARG-365 AND TYR-365; VARIANT HIS-175;

Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder.
Sleat D.E.; Gin R.M.; Sohar I.; Wisniewski K.; Sklower-Brooks S.; Pullarkat R.K.; Palmer D.N.; Lerner T.J.; Boustany R.-M.N.; Uldall P.; Siakotos A.N.; Donnelly R.J.; Lobel P.;
Am. J. Hum. Genet. 64:1511-1523(1999)
Cited for: VARIANTS CLN2 ARG-77; ASN-287; LYS-343; ARG-365; TYR-365; ASP-385; GLU-389; HIS-422; HIS-447; GLU-454 AND LEU-475; VARIANT ARG-100;

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.