ID   TPP1_CANLF              Reviewed;         563 AA.
AC   Q9XSB8; Q45VT9;
DT   31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   27-MAR-2024, entry version 119.
DE   RecName: Full=Tripeptidyl-peptidase 1;
DE            Short=TPP-1;
DE            EC=3.4.14.9;
DE   AltName: Full=Lysosomal pepstatin-insensitive protease;
DE            Short=LPIC;
DE   AltName: Full=Tripeptidyl aminopeptidase;
DE   AltName: Full=Tripeptidyl-peptidase I;
DE            Short=TPP-I;
DE   Flags: Precursor;
GN   Name=TPP1; Synonyms=CLN2;
OS   Canis lupus familiaris (Dog) (Canis familiaris).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX   NCBI_TaxID=9615;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Liu P.-C., Katz M.L., Siakotos A.N., Grob S.E., Johnson G.S.;
RT   "Coding sequence and exon/intron organization of the canine CLN2 gene and
RT   its exclusion as the locus for ceroid lipofuscinosis in English setter
RT   dogs.";
RL   Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-427.
RC   STRAIN=Tibetan terrier;
RX   PubMed=15771740; DOI=10.1111/j.1365-2052.2005.01254.x;
RA   Droegemueller C., Woehlke A., Distl O.;
RT   "Evaluation of the canine TPP1 gene as a candidate for neuronal ceroid
RT   lipofuscinosis in Tibetan terrier and Polish Owczarek Nizinny dogs.";
RL   Anim. Genet. 36:178-179(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-427.
RC   STRAIN=Tibetan terrier;
RA   Sanders D.N., Katz M.L., Johnson G.S.;
RT   "Coding sequence and exon/intron organization of the canine TTP-1 gene and
RT   exclusion of TPP-1 mutations as the cause of hereditary ceroid
RT   lipofuscinosis in English Setter and Tibetan Terrier dogs.";
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Lysosomal serine protease with tripeptidyl-peptidase I
CC       activity. May act as a non-specific lysosomal peptidase which generates
CC       tripeptides from the breakdown products produced by lysosomal
CC       proteinases. Requires substrates with an unsubstituted N-terminus (By
CC       similarity). {ECO:0000250|UniProtKB:Q9EQV6}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Release of an N-terminal tripeptide from a polypeptide, but
CC         also has endopeptidase activity.; EC=3.4.14.9;
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000250|UniProtKB:O14773};
CC       Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000250|UniProtKB:O14773};
CC   -!- SUBUNIT: Monomer. Interacts with CLN5. Interacts with CLN3 (By
CC       similarity). {ECO:0000250|UniProtKB:O14773}.
CC   -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:O14773}.
CC       Melanosome {ECO:0000250|UniProtKB:O14773}.
CC   -!- PTM: Activated by autocatalytic proteolytical processing upon
CC       acidification. N-glycosylation is required for processing and activity
CC       (By similarity). {ECO:0000250|UniProtKB:O14773}.
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DR   EMBL; AF114167; AAD25043.1; -; Genomic_DNA.
DR   EMBL; DQ100344; AAZ38727.1; -; Genomic_DNA.
DR   RefSeq; NP_001013869.1; NM_001013847.1.
DR   AlphaFoldDB; Q9XSB8; -.
DR   SMR; Q9XSB8; -.
DR   STRING; 9615.ENSCAFP00000009732; -.
DR   MEROPS; S53.003; -.
DR   GlyCosmos; Q9XSB8; 5 sites, No reported glycans.
DR   PaxDb; 9612-ENSCAFP00000009732; -.
DR   GeneID; 485337; -.
DR   KEGG; cfa:485337; -.
DR   CTD; 1200; -.
DR   eggNOG; ENOG502QR6D; Eukaryota.
DR   InParanoid; Q9XSB8; -.
DR   OrthoDB; 1405251at2759; -.
DR   Proteomes; UP000002254; Unplaced.
DR   Proteomes; UP000694429; Unplaced.
DR   Proteomes; UP000694542; Unplaced.
DR   Proteomes; UP000805418; Unplaced.
DR   GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR   GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR   GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR   GO; GO:0055037; C:recycling endosome; ISS:UniProtKB.
DR   GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0035727; F:lysophosphatidic acid binding; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0008233; F:peptidase activity; ISS:UniProtKB.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0008236; F:serine-type peptidase activity; ISS:UniProtKB.
DR   GO; GO:0120146; F:sulfatide binding; ISS:UniProtKB.
DR   GO; GO:0008240; F:tripeptidyl-peptidase activity; ISS:UniProtKB.
DR   GO; GO:0045453; P:bone resorption; ISS:UniProtKB.
DR   GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR   GO; GO:0007399; P:nervous system development; ISS:UniProtKB.
DR   GO; GO:0043171; P:peptide catabolic process; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR   CDD; cd04056; Peptidases_S53; 1.
DR   CDD; cd11377; Pro-peptidase_S53; 1.
DR   Gene3D; 3.40.50.200; Peptidase S8/S53 domain; 1.
DR   InterPro; IPR000209; Peptidase_S8/S53_dom.
DR   InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR   InterPro; IPR015366; S53_propep.
DR   InterPro; IPR030400; Sedolisin_dom.
DR   PANTHER; PTHR14218; PROTEASE S8 TRIPEPTIDYL PEPTIDASE I CLN2; 1.
DR   PANTHER; PTHR14218:SF15; TRIPEPTIDYL-PEPTIDASE 1; 1.
DR   Pfam; PF00082; Peptidase_S8; 1.
DR   Pfam; PF09286; Pro-kuma_activ; 1.
DR   SMART; SM00944; Pro-kuma_activ; 1.
DR   SUPFAM; SSF54897; Protease propeptides/inhibitors; 1.
DR   SUPFAM; SSF52743; Subtilisin-like; 1.
DR   PROSITE; PS51695; SEDOLISIN; 1.
PE   3: Inferred from homology;
KW   Autocatalytic cleavage; Calcium; Disulfide bond; Glycoprotein; Hydrolase;
KW   Lysosome; Metal-binding; Protease; Reference proteome; Serine protease;
KW   Signal; Zymogen.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000250|UniProtKB:O14773"
FT   PROPEP          20..195
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000250|UniProtKB:O14773"
FT                   /id="PRO_0000027372"
FT   CHAIN           196..563
FT                   /note="Tripeptidyl-peptidase 1"
FT                   /id="PRO_0000027373"
FT   DOMAIN          199..563
FT                   /note="Peptidase S53"
FT   ACT_SITE        272
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250|UniProtKB:O14773"
FT   ACT_SITE        276
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250|UniProtKB:O14773"
FT   ACT_SITE        475
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250|UniProtKB:O14773"
FT   BINDING         517
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:O14773"
FT   BINDING         518
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:O14773"
FT   BINDING         539
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:O14773"
FT   BINDING         541
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:O14773"
FT   BINDING         543
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:O14773"
FT   CARBOHYD        210
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        222
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        286
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        313
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        443
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        111..122
FT                   /evidence="ECO:0000250|UniProtKB:O14773"
FT   DISULFID        365..526
FT                   /evidence="ECO:0000250|UniProtKB:O14773"
FT   DISULFID        522..537
FT                   /evidence="ECO:0000250|UniProtKB:O14773"
FT   VARIANT         427
FT                   /note="V -> A"
FT                   /evidence="ECO:0000269|PubMed:15771740, ECO:0000269|Ref.3"
SQ   SEQUENCE   563 AA;  61362 MW;  21465A44C34934F4 CRC64;
     MRLRTCLLGL LALCVASKCS YSPEPDQQRT LPPGWVSLGR VDSEEELSLT FALRQQNVER
     LSKLVQAVSD PGSPHYGKYL TLEDVAELVR PSPLTFRTVQ KWLSAAGARN CHSVTTQDFL
     TCWLSVRQAE LLLSGAEFHR YVGGPTEIHV IRSLRPYQLP KALAPHVDFV GGLHRFPPTS
     SLRQRPEPQV SGTVGLHLGV TPSVIRQRYN LTAQDVGSGT TNNSQACAQF LEQYFHASDL
     AEFMRLFGGN FAHQASVARV VGQQGRGRAG IEASLDVEYL MSAGANISTW VYSSPGRHES
     QEPFLQWLLL LSNESALPHV HTVSYGDDED SLSSAYIQRV NTEFMKAAAR GLTLLFASGD
     SGAGCWSVSR RHQFRPSFPA SSPYVTTVGG TSFQNPFRVT TEIVDYISGG GFSNVFPQPS
     YQEEAVVQFL SSSPHLPPSS YFNASGRAYP DVAALSDGYW VVSNSVPIPW VSGTSASTPV
     FGGILSLINE HRLLSGLPPL GFLNPRLYQQ RGAGLFDVTR GCHESCLNEE VQGQGFCSGP
     GWDPVTGWGT PNFPALLKAL IKP
//