TPP1_DANRE
ID TPP1_DANRE Reviewed; 557 AA.
AC F8W2M8; B3DIE8;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 10-APR-2019, sequence version 2.
DT 03-AUG-2022, entry version 56.
DE RecName: Full=Tripeptidyl-peptidase 1 {ECO:0000303|PubMed:23587805};
DE Short=TPP-1 {ECO:0000303|PubMed:23587805};
DE EC=3.4.14.9 {ECO:0000269|PubMed:23587805};
DE AltName: Full=Tripeptidyl aminopeptidase;
DE AltName: Full=Tripeptidyl-peptidase I;
DE Short=TPP-I;
DE Flags: Precursor;
GN Name=tpp1 {ECO:0000303|PubMed:23587805};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|Proteomes:UP000000437};
RN [1] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000312|Proteomes:UP000000437};
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2] {ECO:0000312|EMBL:AAI63102.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF 40-LEU--ASP-557 AND 444-TYR--ASP-557.
RX PubMed=23587805; DOI=10.1093/brain/awt043;
RA Mahmood F., Fu S., Cooke J., Wilson S.W., Cooper J.D., Russell C.;
RT "A zebrafish model of CLN2 disease is deficient in tripeptidyl peptidase 1
RT and displays progressive neurodegeneration accompanied by a reduction in
RT proliferation.";
RL Brain 136:1488-1507(2013).
CC -!- FUNCTION: Lysosomal serine protease with tripeptidyl-peptidase I
CC activity (PubMed:23587805). May act as a non-specific lysosomal
CC peptidase which generates tripeptides from the breakdown products
CC produced by lysosomal proteinases (By similarity). Requires substrates
CC with an unsubstituted N-terminus (By similarity).
CC {ECO:0000250|UniProtKB:O14773, ECO:0000269|PubMed:23587805}.
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 Evidence={ECO:0000269|PubMed:23587805};
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 -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:O14773}.
CC -!- DEVELOPMENTAL STAGE: Expressed in retina at 48 hours post-fertilization
CC (at protein level). Detected in all retinal cell layers but has
CC particularly strong expression in the outer nuclear layer and ganglion
CC cell layer (at protein level). {ECO:0000269|PubMed:23587805}.
CC -!- PTM: Activated by autocatalytic proteolytical processing.
CC {ECO:0000250|UniProtKB:O14773}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein in embryos
CC results in developmental defects from 48 hours post-fertilization
CC onwards, including reduced eye and head size, a curved body, small jaw,
CC and loss of the swim bladder. {ECO:0000269|PubMed:23587805}.
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DR EMBL; BX546455; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC163102; AAI63102.1; -; mRNA.
DR RefSeq; NP_001122270.1; NM_001128798.1.
DR AlphaFoldDB; F8W2M8; -.
DR SMR; F8W2M8; -.
DR STRING; 7955.ENSDARP00000124672; -.
DR MEROPS; S53.008; -.
DR PaxDb; F8W2M8; -.
DR GeneID; 798347; -.
DR KEGG; dre:798347; -.
DR CTD; 1200; -.
DR ZFIN; ZDB-GENE-030131-6654; tpp1.
DR eggNOG; ENOG502QR6D; Eukaryota.
DR HOGENOM; CLU_013783_5_1_1; -.
DR InParanoid; F8W2M8; -.
DR OrthoDB; 1294880at2759; -.
DR PhylomeDB; F8W2M8; -.
DR TreeFam; TF333497; -.
DR PRO; PR:F8W2M8; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0004175; F:endopeptidase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0008240; F:tripeptidyl-peptidase activity; ISS:ZFIN.
DR GO; GO:0007417; P:central nervous system development; IMP:ZFIN.
DR GO; GO:0007626; P:locomotory behavior; IMP:ZFIN.
DR GO; GO:0022008; P:neurogenesis; IMP:ZFIN.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
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 1: Evidence at protein level;
KW Autocatalytic cleavage; Calcium; Disulfide bond; Glycoprotein; Hydrolase;
KW Lysosome; Metal-binding; Protease; Reference proteome; Serine protease;
KW Signal; Zymogen.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT PROPEP 17..190
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT /id="PRO_0000446640"
FT CHAIN 191..557
FT /note="Tripeptidyl-peptidase 1"
FT /evidence="ECO:0000255"
FT /id="PRO_0000446641"
FT DOMAIN 194..557
FT /note="Peptidase S53"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01032"
FT ACT_SITE 266
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01032"
FT ACT_SITE 270
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01032"
FT ACT_SITE 470
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01032"
FT BINDING 512
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT BINDING 513
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT BINDING 538
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 216
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 280
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 307
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 438
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 107..118
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT DISULFID 359..521
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT DISULFID 517..532
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT MUTAGEN 40..557
FT /note="Missing: In sa0011; Lethality occurs from 4 days
FT post-fertilization (dpf) onwards with no survival beyond 7
FT dpf. Severe developmental abnormalities are apparent from
FT 48 hours post-fertilization (hpf) onwards including curved
FT body, small head and a progressive reduction in eye size.
FT At later stages there are signs of pericardial edema and
FT the swim bladder is absent. Neurodegeneration is present in
FT the retina, optic tectum and cerebellum, associated with
FT increased apoptosis and reduced cell proliferation.
FT Locomotor behavior is abnormal with increased movement,
FT aberrant swimming patterns and a twitching phenotype.
FT Significantly reduced peptidase activity and accumulation
FT of the tpp1 substrate, subunit c of mitochondrial ATP
FT synthase."
FT /evidence="ECO:0000269|PubMed:23587805"
FT MUTAGEN 444..557
FT /note="Missing: In hu3587; Viable, with most animal
FT surviving to 3 months of age."
FT /evidence="ECO:0000269|PubMed:23587805"
SQ SEQUENCE 557 AA; 61539 MW; DA04BD8D73DEB1A0 CRC64;
MRVAVFVLSF IWLVNGELLE ADQDAVVPGD WTFLGRVGPL EEVELTFALK QQNVSKMEEL
LKLVSDPDSH QYGKYLSLDE VAALSRPSPL TEKVVENWLR SHGVMDCHTI ITRDFLQCVM
TVEVAEALLP GSKFHRFSKN TKTLLRSTSQ YSVHEDVHQH LDFVGGVHRF PQKRKIVSKG
WEGARQAILG YHLGVTPAVI RNRYNLTAKD VGTAANNSQA VAQFLEQYYH PADLAEFMSL
FGGGFTHMST VERVVGTQGG GKAGIEASLD VEYIMSSGAN ISTWVFTNPG RHESQEPFLQ
WMLLLSNMSA VPWVHTISYG DDEDSLSEAY MNRINIEFMK AGLRGISMLF ASGDSGAGCR
HLTKERNTFR PSFPASSPYV TTVGGTSFQN PFKLSYEVTD YISGGGFSNV FPMPDYQVDA
VRAYLKSVQS LPPQTYFNTT GRAYPDLAAL SDNYWVVSNR VPIPWVSGTS ASTPVVGGIL
SLINDQRFLK GLPALGFINP RLYKMQGKGL YDVTVGCHLS CLDDKVEGKG FCASPSWDPV
TGWGTPNYPV FLASLMD
