TPP1_PANTR
ID TPP1_PANTR Reviewed; 563 AA.
AC Q5IS74;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 111.
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 Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15620360; DOI=10.1016/j.cell.2004.11.040;
RA Dorus S., Vallender E.J., Evans P.D., Anderson J.R., Gilbert S.L.,
RA Mahowald M., Wyckoff G.J., Malcom C.M., Lahn B.T.;
RT "Accelerated evolution of nervous system genes in the origin of Homo
RT sapiens.";
RL Cell 119:1027-1040(2004).
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; AY665254; AAV74292.1; -; mRNA.
DR RefSeq; NP_001013025.1; NM_001013007.1.
DR AlphaFoldDB; Q5IS74; -.
DR SMR; Q5IS74; -.
DR STRING; 9598.ENSPTRP00000005774; -.
DR MEROPS; S53.003; -.
DR PaxDb; Q5IS74; -.
DR Ensembl; ENSPTRT00000006261; ENSPTRP00000005774; ENSPTRG00000003299.
DR GeneID; 450999; -.
DR KEGG; ptr:450999; -.
DR CTD; 1200; -.
DR VGNC; VGNC:10187; TPP1.
DR eggNOG; ENOG502QR6D; Eukaryota.
DR GeneTree; ENSGT00390000008684; -.
DR HOGENOM; CLU_013783_5_1_1; -.
DR InParanoid; Q5IS74; -.
DR OMA; HDEMKRM; -.
DR OrthoDB; 1294880at2759; -.
DR TreeFam; TF333497; -.
DR Proteomes; UP000002277; Chromosome 11.
DR Bgee; ENSPTRG00000003299; Expressed in cortex of kidney and 21 other tissues.
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; IBA:GO_Central.
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; IBA:GO_Central.
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; IEA:Ensembl.
DR GO; GO:1905146; P:lysosomal protein catabolic process; IEA:Ensembl.
DR GO; GO:0007040; P:lysosome organization; IEA:Ensembl.
DR GO; GO:0007399; P:nervous system development; ISS:UniProtKB.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl.
DR GO; GO:0043171; P:peptide catabolic process; ISS:UniProtKB.
DR GO; GO:0070198; P:protein localization to chromosome, telomeric region; IEA:Ensembl.
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; -; 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 Pfam; PF00082; Peptidase_S8; 1.
DR Pfam; PF09286; Pro-kuma_activ; 1.
DR SMART; SM00944; Pro-kuma_activ; 1.
DR SUPFAM; SSF52743; SSF52743; 1.
DR PROSITE; PS51695; SEDOLISIN; 1.
PE 2: Evidence at transcript level;
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_0000027380"
FT CHAIN 196..563
FT /note="Tripeptidyl-peptidase 1"
FT /id="PRO_0000027381"
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"
SQ SEQUENCE 563 AA; 61295 MW; F8B1991276E8F361 CRC64;
MGLQACLLGL FALILSGKCS YSPEPDQRRT LPPGWVSLGR ADPEEELSLT FALRQQNVER
LSELVQAVSD PSSPQYGKYL TLENVADLVR PSPLTLRTVQ KWLLAAGARK CHSVITQDFL
TCWLSIRQAE LLLPGAEFHH YVGGPTETHV VRSPHPYQLP QALAPHVDFV GGLHRFPPTS
SLRQRPEPQV TGTVGLHLGV TPSVIRKRYN LTSQDVGSGT SNNSQACAQF LEQYFHDSDL
AQFMRLFGGN FAHQASVARV VGQQGRGRAG IEASLDVQYL MSAGANISTW VYSSPGRHEG
QEPFLQWLML LSNESALPHV HTVSYGDDED SLSSAYIQRV NTELMKAAAR GLTLLFASGD
SGAGCWSVSG RHQFRPTFPA SSPYVTTVGG TSFQEPFLIT NEIVDYISGG GFSNVFPRPS
YQEEAVTKFL SSSPHLPPSS YFNASGRAYP DVAALSDGYW VVSNRVPIPW VSGTSASTPV
FGGILSLINE HRILSGRPPL GFLNPRLYQQ HGAGLFDVTR GCHESCLDEE VEGQGFCSGP
GWDPVTGWGT PNFPALLKTL LNP
