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tripeptidyl-peptidase 1; TPP-1; cell growth-inhibiting gene 1 protein; lysosomal pepstatin-insensitive protease; LPIC; tripeptidyl aminopeptidase; tripeptidyl-peptidase I; TPP-I (TPP1, GIG1, UNQ267/PRO304)
Function:
- lysosomal serine protease with tripeptidyl-peptidase 1 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 (putative)
- release of an N-terminal tripeptide from a polypeptide, but also has endopeptidase activity
- activated by autocatalytic proteolytical processing upon acidification
Cofactor: binds 1 Ca+2 per subunit
Structure:
- monomer
- N-glycosylation
- N-glycosylation is required for processing & activity
- belongs to the peptidase S53 family
Compartment:
- lysosome, melanosome
Alternative splicing: named isoforms=2
Expression:
- detected in all tissues examined
- highest levels in heart & placenta
- lower & relatively similar levels in other tissues
Pathology:
- defects in TPP1 are the cause of neuronal ceroid lipofuscinosis type 2
Laboratory:
- tripeptidyl peptidase 1 in dried blood spot
- tripeptidyl peptidase 1 in fibroblasts
- tripeptidyl peptidase 1 in leukocytes
General
aminopeptidase
Ca+2 binding protein
glycoprotein
Properties
SIZE: entity length = 563 aa
MW = 61 kD
COMPARTMENT: lysosome
MOTIF: signal sequence {1-19}
cysteine residue {C111}
MODIFICATION: cysteine residue {C122}
cysteine residue {C122}
MODIFICATION: cysteine residue {C111}
N-glycosylation site {N210}
N-glycosylation site {N222}
glutamate residue {E272}
aspartate residue {D276}
N-glycosylation site {N286}
N-glycosylation site {N313}
cysteine residue {C365}
MODIFICATION: cysteine residue {C526}
N-glycosylation site {N443}
serine residue {S475}
Ca+2-binding site
SITE: 517-517
Ca+2-binding site
SITE: 518-518
cysteine residue {C522}
MODIFICATION: cysteine residue {C537}
cysteine residue {C526}
MODIFICATION: cysteine residue {C365}
cysteine residue {C537}
MODIFICATION: cysteine residue {C522}
Ca+2-binding site
SITE: 539-539
Ca+2-binding site
SITE: 541-541
Ca+2-binding site
SITE: 543-543
Database Correlations
OMIM correlations
MORBIDMAP 607998
UniProt O14773
PFAM correlations
Entrez Gene 1200
Kegg hsa:1200
ENZYME 3.4.14.9
References
- UniProt :accession O14773
- NCL CLN2; Neural ceroid lipofuscinoses mutation db
http://www.ucl.ac.uk/ncl/cln2.shtml
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/TPP1