TPP1_MACFA
ID TPP1_MACFA Reviewed; 563 AA.
AC Q60HH1; Q8HXY1;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 85.
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; ORFNames=QccE-12010, QtrA-16970;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex, and Temporal cortex;
RA Kusuda J., Osada N., Tanuma R., Hirata M., Sugano S., Hashimoto K.;
RT "Isolation and characterization of cDNA for macaque neurological disease
RT genes.";
RL Submitted (OCT-2003) 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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD51944.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB083308; BAC20587.1; -; mRNA.
DR EMBL; AB125156; BAD51944.1; ALT_INIT; mRNA.
DR AlphaFoldDB; Q60HH1; -.
DR SMR; Q60HH1; -.
DR STRING; 9541.XP_005578832.1; -.
DR MEROPS; S53.003; -.
DR PRIDE; Q60HH1; -.
DR VEuPathDB; HostDB:ENSMFAG00000033375; -.
DR eggNOG; ENOG502QR6D; Eukaryota.
DR OMA; HDEMKRM; -.
DR Proteomes; UP000233100; Chromosome 14.
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: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; -; 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_0000027376"
FT CHAIN 196..563
FT /note="Tripeptidyl-peptidase 1"
FT /id="PRO_0000027377"
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 CONFLICT 425
FT /note="A -> V (in Ref. 1; BAC20587)"
FT /evidence="ECO:0000305"
FT CONFLICT 463
FT /note="S -> N (in Ref. 1; BAC20587)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 563 AA; 61245 MW; FCB1014BB43CABA2 CRC64;
MGLQACLLGL FALILSGKCS YSPEPDQRRT LPPGWVSLGR ADPEEELSLT FALRQQNLER
LSELVQAVSD PNSPQYGKYL TLENVADLVR PSPLTLHMVQ KWLLAAGAQK CHSVITQDFL
TCWLSIRQAE LLLPGAEFHH YVGGPTETHV VRSPRPYQLP QALAPHVDFV GGLHRFPPTS
SLRQRPEPQV TGTVGLHLGV TPSVIRKRYN LTSQDVGSGT SNNSQACAQF LEQYFHDSDL
AQFMRLFGGN FAHQASVTRV VGQQGRGRAG IEASLDVQYL MSAGANISTW VYSSPGRHEG
QEPFLQWLML LSNESALPHV HTVSYGDEED SLSSAYIQRV NTELMKAAAR GLTLLFASGD
SGAGCWSVSG RHQFRPTFPA SSPYVTTVGG TSFQEPFLIT NEIVDYISGG GFSNVFPRPS
YQEEAVAKFL SSSPHLPPSG YFNASGRAYP DVAALSDGYW VVSNRVPIPW VSGTSASTPV
FGGLLSLINE HRILSGRPPL GFLNPRLYQQ HGAGLFDVTH GCHASCLDEE VEGQGFCSGP
GWDPVTGWGT PNFPALLKTL LNP
