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
//
