TPP1_MOUSE
ID TPP1_MOUSE Reviewed; 562 AA.
AC O89023; Q543Q8; Q9QUS7;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Tripeptidyl-peptidase 1;
DE Short=TPP-1;
DE EC=3.4.14.9 {ECO:0000269|PubMed:28464005};
DE AltName: Full=Lysosomal pepstatin-insensitive protease;
DE Short=LPIC;
DE AltName: Full=Tripeptidyl aminopeptidase;
DE AltName: Full=Tripeptidyl-peptidase I;
DE Short=TPP-I;
DE Flags: Precursor;
GN Name=Tpp1; Synonyms=Cln2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9989590; DOI=10.1016/s0014-5793(98)01683-4;
RA Vines D.J., Warburton M.J.;
RT "Classical late infantile neuronal ceroid lipofuscinosis fibroblasts are
RT deficient in lysosomal tripeptidyl peptidase I.";
RL FEBS Lett. 443:131-135(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10556422; DOI=10.1007/s003359901160;
RA Katz M.L., Liu P.-C., Grob-Nunn S.E., Shibuya H., Johnson G.S.;
RT "Characterization and chromosomal mapping of a mouse ortholog of the late-
RT infantile ceroid-lipofuscinosis gene CLN2.";
RL Mamm. Genome 10:1050-1053(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE.
RA Sleat D.E., Lobel P.;
RT "Murine homologue of the lysosomal pepstatin insensitive protease which is
RT deficient in human classical late infantile neuronal ceroid
RT lipofuscinosis.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Head, and Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Retina;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-221.
RC TISSUE=Epidermis;
RX PubMed=16170054; DOI=10.1074/mcp.m500203-mcp200;
RA Uematsu R., Furukawa J., Nakagawa H., Shinohara Y., Deguchi K., Monde K.,
RA Nishimura S.;
RT "High throughput quantitative glycomics and glycoform-focused proteomics of
RT murine dermis and epidermis.";
RL Mol. Cell. Proteomics 4:1977-1989(2005).
RN [7]
RP INTERACTION WITH CLN5, AND SUBCELLULAR LOCATION.
RX PubMed=19941651; DOI=10.1186/1471-2121-10-83;
RA Lyly A., von Schantz C., Heine C., Schmiedt M.L., Sipilae T., Jalanko A.,
RA Kyttaelae A.;
RT "Novel interactions of CLN5 support molecular networking between neuronal
RT ceroid lipofuscinosis proteins.";
RL BMC Cell Biol. 10:83-83(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 207-ARG--PRO-562.
RX PubMed=28464005; DOI=10.1371/journal.pone.0176526;
RA Geraets R.D., Langin L.M., Cain J.T., Parker C.M., Beraldi R., Kovacs A.D.,
RA Weimer J.M., Pearce D.A.;
RT "A tailored mouse model of CLN2 disease: A nonsense mutant for testing
RT personalized therapies.";
RL PLoS ONE 12:E0176526-E0176526(2017).
CC -!- FUNCTION: Lysosomal serine protease with tripeptidyl-peptidase I
CC activity (PubMed:28464005). 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:28464005}.
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:28464005};
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 (By similarity). Interacts with CLN5
CC (PubMed:19941651). Interacts with CLN3 (By similarity).
CC {ECO:0000250|UniProtKB:O14773, ECO:0000269|PubMed:19941651}.
CC -!- INTERACTION:
CC O89023; Q91WC1: Pot1; NbExp=2; IntAct=EBI-7051084, EBI-7051001;
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:19941651}.
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=CAA09863.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AJ011912; CAA09863.1; ALT_INIT; mRNA.
DR EMBL; AF124599; AAD32573.1; -; Genomic_DNA.
DR EMBL; AF111172; AAD03083.1; -; mRNA.
DR EMBL; AK002418; BAB22085.1; -; mRNA.
DR EMBL; AK048279; BAC33293.1; -; mRNA.
DR EMBL; AK170781; BAE42026.1; -; mRNA.
DR EMBL; BC024820; AAH24820.1; -; mRNA.
DR CCDS; CCDS21661.1; -.
DR RefSeq; NP_034036.1; NM_009906.6.
DR AlphaFoldDB; O89023; -.
DR SMR; O89023; -.
DR BioGRID; 198754; 5.
DR IntAct; O89023; 1.
DR MINT; O89023; -.
DR STRING; 10090.ENSMUSP00000033184; -.
DR MEROPS; S53.003; -.
DR GlyConnect; 2800; 9 N-Linked glycans (3 sites).
DR GlyGen; O89023; 5 sites, 9 N-linked glycans (3 sites).
DR iPTMnet; O89023; -.
DR PhosphoSitePlus; O89023; -.
DR EPD; O89023; -.
DR jPOST; O89023; -.
DR MaxQB; O89023; -.
DR PaxDb; O89023; -.
DR PeptideAtlas; O89023; -.
DR PRIDE; O89023; -.
DR ProteomicsDB; 259169; -.
DR Antibodypedia; 23932; 437 antibodies from 39 providers.
DR DNASU; 12751; -.
DR Ensembl; ENSMUST00000033184; ENSMUSP00000033184; ENSMUSG00000030894.
DR GeneID; 12751; -.
DR KEGG; mmu:12751; -.
DR UCSC; uc009izg.1; mouse.
DR CTD; 1200; -.
DR MGI; MGI:1336194; Tpp1.
DR VEuPathDB; HostDB:ENSMUSG00000030894; -.
DR eggNOG; ENOG502QR6D; Eukaryota.
DR GeneTree; ENSGT00390000008684; -.
DR HOGENOM; CLU_013783_5_1_1; -.
DR InParanoid; O89023; -.
DR OMA; HDEMKRM; -.
DR OrthoDB; 1294880at2759; -.
DR PhylomeDB; O89023; -.
DR TreeFam; TF333497; -.
DR BRENDA; 3.4.14.9; 3474.
DR BioGRID-ORCS; 12751; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Tpp1; mouse.
DR PRO; PR:O89023; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; O89023; protein.
DR Bgee; ENSMUSG00000030894; Expressed in choroid plexus of fourth ventricle and 257 other tissues.
DR ExpressionAtlas; O89023; baseline and differential.
DR Genevisible; O89023; MM.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
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:0042277; F:peptide binding; ISO:MGI.
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:MGI.
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; IMP:MGI.
DR GO; GO:0007040; P:lysosome organization; IMP:MGI.
DR GO; GO:0007399; P:nervous system development; ISS:UniProtKB.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IMP:MGI.
DR GO; GO:0043171; P:peptide catabolic process; ISS:UniProtKB.
DR GO; GO:0030163; P:protein catabolic process; ISO:MGI.
DR GO; GO:0070198; P:protein localization to chromosome, telomeric region; ISO:MGI.
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; IPR036852; Peptidase_S8/S53_dom_sf.
DR InterPro; IPR015366; S53_propep.
DR InterPro; IPR030400; Sedolisin_dom.
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..19
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT PROPEP 20..194
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT /id="PRO_0000027378"
FT CHAIN 195..562
FT /note="Tripeptidyl-peptidase 1"
FT /id="PRO_0000027379"
FT DOMAIN 198..562
FT /note="Peptidase S53"
FT ACT_SITE 271
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT ACT_SITE 275
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT ACT_SITE 474
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT BINDING 516
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
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 538
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT BINDING 540
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT BINDING 542
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT CARBOHYD 209
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 221
FT /note="N-linked (GlcNAc...) (high mannose) asparagine"
FT /evidence="ECO:0000269|PubMed:16170054"
FT CARBOHYD 285
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 442
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 111..122
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT DISULFID 364..525
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT DISULFID 521..536
FT /evidence="ECO:0000250|UniProtKB:O14773"
FT MUTAGEN 207..562
FT /note="Missing: Premature lethality from 3 months of age,
FT with no survival beyond 6 months. Progressive defects in
FT motor coordination and balance from age 3 months,
FT accompanied by a twitching phenotype. Marked degeneration
FT of astrocytes in the cerebrum. Significant loss of
FT peptidase activity, leading to accumulation of the TPP1
FT substrate ATP5MC1 in lysosomes."
FT /evidence="ECO:0000269|PubMed:28464005"
FT CONFLICT 1
FT /note="M -> V (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 562
FT /note="P -> LDPFVP (in Ref. 1)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 562 AA; 61342 MW; 0AF8163EA1A66396 CRC64;
MGLQARLLGL LALVIAGKCT YNPEPDQRWM LPPGWVSLGR VDPEEELSLT FALKQRNLER
LSELVQAVSD PSSPQYGKYL TLEDVAELVQ PSPLTLLTVQ KWLSAAGARN CDSVTTQDFL
TCWLSVRQAE LLLPGAEFHR YVGGPTKTHV IRSPHPYQLP QALAPHVDFV GGLHRFPPSS
PRQRPEPQQV GTVSLHLGVT PSVLRQRYNL TAKDVGSGTT NNSQACAQFL EQYFHNSDLT
EFMRLFGGSF THQASVAKVV GKQGRGRAGI EASLDVEYLM SAGANISTWV YSSPGRHEAQ
EPFLQWLLLL SNESSLPHVH TVSYGDDEDS LSSIYIQRVN TEFMKAAARG LTLLFASGDT
GAGCWSVSGR HKFRPSFPAS SPYVTTVGGT SFKNPFLITD EVVDYISGGG FSNVFPRPPY
QEEAVAQFLK SSSHLPPSSY FNASGRAYPD VAALSDGYWV VSNMVPIPWV SGTSASTPVF
GGILSLINEH RILNGRPPLG FLNPRLYQQH GTGLFDVTHG CHESCLNEEV EGQGFCSGPG
WDPVTGWGTP NFPALLKTLL NP
