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UniProtKB/Swiss-Prot O14773: Variant p.Arg447His

Tripeptidyl-peptidase 1
Gene: TPP1
Variant information

Variant position:  447
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 Arginine (R) to Histidine (H) at position 447 (R447H, p.Arg447His).
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 basic (R) to medium size and polar (H)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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 very low residual enzyme activity; altered intracellular trafficking; demonstrates enhanced processing in response to folding improvement treatment; shows a five fold increase under permissive temperature conditions.
Any additional useful information about the variant.

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



Sequence information

Variant position:  447
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:   TKFLSSSPHLPPSSYFNASG  R AYPDVAALSDGYWVVSNRVP
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                         TKFLSSSPHLPPSS---YF--NASGRAYPDVAALSDGYWVVSNRVP

                              VQFLSSSPHLPPSS---YF--NASGRAYPDVAALSDGYWVV

Chimpanzee                    TKFLSSSPHLPPSS---YF--NASGRAYPDVAALSDGYWVV

Mouse                         AQFLKSSSHLPPSS---YF--NASGRAYPDVAALSDGYWVV

Rat                           AQFLKSSSHLPPSS---YF--NASGRAYPDVAALSDGYWVV

Bovine                        TRYLSSSPHLPPSS---YF--NASGRAYPDVAALSDGYWVV

Zebrafish                     RAYLKSVQSLPPQT---YF--NTTGRAYPDLAALSDNYWVV

Slime mold                    SSYIEWLNG-SLSS---FY--NQSGRGFPDISSFSENVVIL

Baker's yeast                 -----------------YYCGDAAGRK----KDFSDSDIKF

Fission yeast                 RNWMDDIKGLGLSAEHGSFVRKPHSTTWINLAELLDMSWKK

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
Glycosylation 443 – 443 N-linked (GlcNAc...) asparagine
Disulfide bond 365 – 526
Beta strand 446 – 449


Literature citations

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;

Expression and analysis of CLN2 variants in CHO cells: Q100R represents a polymorphism, and G389E and R447H represent loss-of-function mutations.
Lin L.; Lobel P.;
Hum. Mutat. 18:165-165(2001)
Cited for: CHARACTERIZATION OF VARIANTS ARG-100; GLU-389 AND HIS-447;

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.