ID:TPP1_HUMAN DESCRIPTION: RecName: Full=Tripeptidyl-peptidase 1; Short=TPP-1; EC=3.4.14.9; AltName: Full=Cell growth-inhibiting gene 1 protein; AltName: Full=Lysosomal pepstatin-insensitive protease; Short=LPIC; AltName: Full=Tripeptidyl aminopeptidase; AltName: Full=Tripeptidyl-peptidase I; Short=TPP-I; Flags: Precursor; FUNCTION: Lysosomal serine protease with tripeptidyl-peptidase I activity. May act as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases. Requires substrates with an unsubstituted N-terminus (By similarity). CATALYTIC ACTIVITY: Release of an N-terminal tripeptide from a polypeptide, but also has endopeptidase activity. COFACTOR: Binds 1 calcium ion per subunit. SUBUNIT: Monomer. SUBCELLULAR LOCATION: Lysosome. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. TISSUE SPECIFICITY: Detected in all tissues examined with highest levels in heart and placenta and relatively similar levels in other tissues. PTM: Activated by autocatalytic proteolytical processing upon acidification. N-glycosylation is required for processing and activity. DISEASE: Defects in TPP1 are the cause of neuronal ceroid lipofuscinosis type 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. SIMILARITY: Belongs to the peptidase S53 family. SEQUENCE CAUTION: Sequence=AAM08412.1; Type=Miscellaneous discrepancy; Note=Incorrectly indicated as originating from bovine; Sequence=AAQ88866.1; Type=Frameshift; Positions=551; WEB RESOURCE: Name=NCL CLN2; Note=Neural Ceroid Lipofuscinoses mutation db; URL="http://www.ucl.ac.uk/ncl/cln2.shtml"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TPP1"; WEB RESOURCE: Name=Mendelian genes trieptidyl peptidase I (TPP1); Note=Leiden Open Variation Database (LOVD); URL="http://www.lovd.nl/TPP1";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O14773
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006508 proteolysis GO:0006629 lipid metabolic process GO:0007040 lysosome organization GO:0007399 nervous system development GO:0007417 central nervous system development GO:0030163 protein catabolic process GO:0030855 epithelial cell differentiation GO:0036498 IRE1-mediated unfolded protein response GO:0043171 peptide catabolic process GO:0045453 bone resorption GO:0050885 neuromuscular process controlling balance