ID   TPP1_RAT                Reviewed;         563 AA.
AC   Q9EQV6;
DT   31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   08-NOV-2023, entry version 129.
DE   RecName: Full=Tripeptidyl-peptidase 1;
DE            Short=TPP-1;
DE            EC=3.4.14.9;
DE   AltName: Full=Tripeptidyl aminopeptidase;
DE   AltName: Full=Tripeptidyl-peptidase I;
DE            Short=TPP-I;
DE   Flags: Precursor;
GN   Name=Tpp1; Synonyms=Cln2;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Liver;
RA   Du P., Kato S., Li Y., Maeda T., Yamane T., Yamamoto S., Fujiwara M.,
RA   Yamamoto Y., Nishi K., Ohkubo I.;
RT   "Rat tripeptidyl peptidase I: its purification and molecular cloning.";
RL   Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   PROTEIN SEQUENCE OF 196-217; 374-392 AND 395-429, FUNCTION, AND
RP   BIOPHYSICOCHEMICAL PROPERTIES.
RC   TISSUE=Spleen;
RX   PubMed=9659384; DOI=10.1016/s0167-4838(98)00012-0;
RA   Vines D.J., Warburton M.J.;
RT   "Purification and characterisation of a tripeptidyl aminopeptidase I from
RT   rat spleen.";
RL   Biochim. Biophys. Acta 1384:233-242(1998).
RN   [3]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-222, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=24090084; DOI=10.1021/pr400783j;
RA   Parker B.L., Thaysen-Andersen M., Solis N., Scott N.E., Larsen M.R.,
RA   Graham M.E., Packer N.H., Cordwell S.J.;
RT   "Site-specific glycan-peptide analysis for determination of N-glycoproteome
RT   heterogeneity.";
RL   J. Proteome Res. 12:5791-5800(2013).
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.
CC       {ECO:0000269|PubMed:9659384}.
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   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 4. Unstable above pH 7. {ECO:0000269|PubMed:9659384};
CC   -!- SUBUNIT: Monomer. Interacts with CLN5 (By similarity). Interacts with
CC       CLN3 (By 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; AB043870; BAB18570.1; -; mRNA.
DR   RefSeq; NP_112647.1; NM_031357.1.
DR   AlphaFoldDB; Q9EQV6; -.
DR   SMR; Q9EQV6; -.
DR   IntAct; Q9EQV6; 1.
DR   STRING; 10116.ENSRNOP00000026280; -.
DR   MEROPS; S53.003; -.
DR   GlyCosmos; Q9EQV6; 5 sites, 7 glycans.
DR   GlyGen; Q9EQV6; 5 sites, 7 N-linked glycans (3 sites).
DR   iPTMnet; Q9EQV6; -.
DR   PhosphoSitePlus; Q9EQV6; -.
DR   jPOST; Q9EQV6; -.
DR   PaxDb; 10116-ENSRNOP00000026280; -.
DR   GeneID; 83534; -.
DR   KEGG; rno:83534; -.
DR   UCSC; RGD:621296; rat.
DR   AGR; RGD:621296; -.
DR   CTD; 1200; -.
DR   RGD; 621296; Tpp1.
DR   eggNOG; ENOG502QR6D; Eukaryota.
DR   InParanoid; Q9EQV6; -.
DR   OrthoDB; 1405251at2759; -.
DR   PhylomeDB; Q9EQV6; -.
DR   BRENDA; 3.4.14.9; 5301.
DR   PRO; PR:Q9EQV6; -.
DR   Proteomes; UP000002494; 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; IDA:RGD.
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:0042277; F:peptide binding; IDA:RGD.
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; IDA:RGD.
DR   GO; GO:0045453; P:bone resorption; ISS:UniProtKB.
DR   GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR   GO; GO:0030855; P:epithelial cell differentiation; ISO:RGD.
DR   GO; GO:1905146; P:lysosomal protein catabolic process; ISO:RGD.
DR   GO; GO:0007040; P:lysosome organization; ISO:RGD.
DR   GO; GO:0007399; P:nervous system development; ISS:UniProtKB.
DR   GO; GO:0050885; P:neuromuscular process controlling balance; ISO:RGD.
DR   GO; GO:0043171; P:peptide catabolic process; ISS:UniProtKB.
DR   GO; GO:0030163; P:protein catabolic process; IDA:RGD.
DR   GO; GO:0070198; P:protein localization to chromosome, telomeric region; ISO:RGD.
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   1: Evidence at protein level;
KW   Autocatalytic cleavage; Calcium; Direct protein sequencing; Disulfide bond;
KW   Glycoprotein; Hydrolase; Lysosome; Metal-binding; Protease;
KW   Reference proteome; Serine protease; 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:0000269|PubMed:9659384"
FT                   /id="PRO_0000027384"
FT   CHAIN           196..563
FT                   /note="Tripeptidyl-peptidase 1"
FT                   /id="PRO_0000027385"
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:0007744|PubMed:24090084"
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   CONFLICT        210
FT                   /note="N -> A (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        216..217
FT                   /note="VG -> SQ (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        389..391
FT                   /note="GGT -> SPP (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   563 AA;  61332 MW;  B54F3C86205DFEC1 CRC64;
     MGLQARFLGL LALVIAGKCT HSPEPDQRWM LPPGWVSLGR VDPEEELSLT FALKQQNLDR
     LSELVQAVSD PSSPRYGKYL TLEDVAELVQ PSPLTLRTVQ KWLLAAGARD CHSVTTQDFL
     TCWLSVRQAE LLLPGAEFHR YVGGPAKTHI IRSPHPYQLP QALAPHVDLV AGLHRFPPLS
     SPRQRPEPQG VGPVGLHLGV TPSVLRQRYN LTARDVGSGT TNNSQACAQF LEQYFHNSDL
     TEFMRLFGSS FAHQASVARV VGKQGRGRAG IEASLDVEYL MSAGANISTW VYSSPGRHEA
     QEPFLQWLLL LSNESSLPHV HTVSYGDDED SLSSVYIQRV NTEFMKAAAR GLTLLFASGD
     TGAGCWSVSG RHKFRPSFPA SSPYVTTVGG TSFKNPFLVT NEVVDYISGG GFSNVFPQPS
     YQEEAVAQFL KSSSHLPPSS YFNASGRAYP DVAALSDGYW VVSNMVPIPW VSGTSASTPV
     FGGILSLINE HRLLNGRPPL GFLNPRLYQQ HGAGLFDVTH GCHESCLNEE VEGQGFCSGP
     GWDPVTGWGT PNFPALLKTL LNP
//