UniProtKB - O89023 (TPP1_MOUSE)
Tripeptidyl-peptidase 1
Tpp1
Functioni
Lysosomal serine protease with tripeptidyl-peptidase I activity (PubMed:28464005).
May act as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases (By similarity).
Requires substrates with an unsubstituted N-terminus (By similarity).
By similarity1 PublicationCatalytic activityi
- Release of an N-terminal tripeptide from a polypeptide, but also has endopeptidase activity.1 Publication EC:3.4.14.9
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 271 | Charge relay systemBy similarity | 1 | |
Active sitei | 275 | Charge relay systemBy similarity | 1 | |
Active sitei | 474 | Charge relay systemBy similarity | 1 | |
Metal bindingi | 516 | CalciumBy similarity | 1 | |
Metal bindingi | 517 | Calcium; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 538 | Calcium; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 540 | Calcium; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 542 | CalciumBy similarity | 1 |
GO - Molecular functioni
- endopeptidase activity Source: UniProtKB
- lysophosphatidic acid binding Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- peptidase activity Source: UniProtKB
- peptide binding Source: MGI
- serine-type endopeptidase activity Source: InterPro
- serine-type peptidase activity Source: UniProtKB
- sulfatide binding Source: UniProtKB
- tripeptidyl-peptidase activity Source: MGI
GO - Biological processi
- bone resorption Source: UniProtKB
- central nervous system development Source: GO_Central
- epithelial cell differentiation Source: Ensembl
- lysosomal protein catabolic process Source: MGI
- lysosome organization Source: MGI
- nervous system development Source: UniProtKB
- neuromuscular process controlling balance Source: MGI
- peptide catabolic process Source: UniProtKB
- protein localization to chromosome, telomeric region Source: MGI
- proteolysis Source: UniProtKB
Keywordsi
Molecular function | Hydrolase, Protease, Serine protease |
Ligand | Calcium, Metal-binding |
Enzyme and pathway databases
BRENDAi | 3.4.14.9, 3474 |
Protein family/group databases
MEROPSi | S53.003 |
Names & Taxonomyi
Protein namesi | Recommended name: Tripeptidyl-peptidase 1 (EC:3.4.14.91 Publication)Short name: TPP-1 Alternative name(s): Lysosomal pepstatin-insensitive protease Short name: LPIC Tripeptidyl aminopeptidase Tripeptidyl-peptidase I Short name: TPP-I |
Gene namesi | Name:Tpp1 Synonyms:Cln2 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1336194, Tpp1 |
VEuPathDBi | HostDB:ENSMUSG00000030894 |
Subcellular locationi
Lysosome
- Lysosome 1 Publication
Other locations
- Melanosome By similarity
Endosome
- recycling endosome Source: UniProtKB
Golgi apparatus
- Golgi apparatus Source: UniProtKB
Lysosome
- lysosome Source: UniProtKB
Mitochondrion
- mitochondrion Source: MGI
Other locations
- melanosome Source: UniProtKB-SubCell
- membrane raft Source: UniProtKB
Keywords - Cellular componenti
LysosomePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 207 – 562 | Missing : Premature lethality from 3 months of age, with no survival beyond 6 months. Progressive defects in motor coordination and balance from age 3 months, accompanied by a twitching phenotype. Marked degeneration of astrocytes in the cerebrum. Significant loss of peptidase activity, leading to accumulation of the TPP1 substrate ATP5MC1 in lysosomes. 1 PublicationAdd BLAST | 356 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 19 | By similarityAdd BLAST | 19 | |
PropeptideiPRO_0000027378 | 20 – 194 | Removed in mature formBy similarityAdd BLAST | 175 | |
ChainiPRO_0000027379 | 195 – 562 | Tripeptidyl-peptidase 1Add BLAST | 368 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 111 ↔ 122 | By similarity | ||
Glycosylationi | 209 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 221 | N-linked (GlcNAc...) (high mannose) asparagine1 Publication | 1 | |
Glycosylationi | 285 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 312 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 364 ↔ 525 | By similarity | ||
Glycosylationi | 442 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 521 ↔ 536 | By similarity |
Post-translational modificationi
Keywords - PTMi
Autocatalytic cleavage, Disulfide bond, Glycoprotein, ZymogenProteomic databases
EPDi | O89023 |
jPOSTi | O89023 |
MaxQBi | O89023 |
PaxDbi | O89023 |
PeptideAtlasi | O89023 |
PRIDEi | O89023 |
ProteomicsDBi | 259169 |
PTM databases
GlyConnecti | 2800, 9 N-Linked glycans (3 sites) |
GlyGeni | O89023, 5 sites, 9 N-linked glycans (3 sites) |
iPTMneti | O89023 |
PhosphoSitePlusi | O89023 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000030894, Expressed in ileum and 313 other tissues |
Genevisiblei | O89023, MM |
Interactioni
Subunit structurei
Monomer (By similarity).
Interacts with CLN5 (PubMed:19941651).
Interacts with CLN3 (By similarity).
By similarity1 PublicationBinary interactionsi
O89023
With | #Exp. | IntAct |
---|---|---|
Pot1 [Q91WC1] | 2 | EBI-7051084,EBI-7051001 |
Protein-protein interaction databases
BioGRIDi | 198754, 5 interactors |
IntActi | O89023, 1 interactor |
MINTi | O89023 |
STRINGi | 10090.ENSMUSP00000033184 |
Miscellaneous databases
RNActi | O89023, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 198 – 562 | Peptidase S53Add BLAST | 365 |
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502QR6D, Eukaryota |
GeneTreei | ENSGT00390000008684 |
HOGENOMi | CLU_013783_5_1_1 |
InParanoidi | O89023 |
OMAi | HDEMKRM |
OrthoDBi | 1294880at2759 |
PhylomeDBi | O89023 |
TreeFami | TF333497 |
Family and domain databases
CDDi | cd04056, Peptidases_S53, 1 hit cd11377, Pro-peptidase_S53, 1 hit |
Gene3Di | 3.40.50.200, 1 hit |
InterProi | View protein in InterPro IPR036852, Peptidase_S8/S53_dom_sf IPR015366, S53_propep IPR030400, Sedolisin_dom |
Pfami | View protein in Pfam PF09286, Pro-kuma_activ, 1 hit |
SMARTi | View protein in SMART SM00944, Pro-kuma_activ, 1 hit |
SUPFAMi | SSF52743, SSF52743, 1 hit |
PROSITEi | View protein in PROSITE PS51695, SEDOLISIN, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MGLQARLLGL LALVIAGKCT YNPEPDQRWM LPPGWVSLGR VDPEEELSLT
60 70 80 90 100
FALKQRNLER LSELVQAVSD PSSPQYGKYL TLEDVAELVQ PSPLTLLTVQ
110 120 130 140 150
KWLSAAGARN CDSVTTQDFL TCWLSVRQAE LLLPGAEFHR YVGGPTKTHV
160 170 180 190 200
IRSPHPYQLP QALAPHVDFV GGLHRFPPSS PRQRPEPQQV GTVSLHLGVT
210 220 230 240 250
PSVLRQRYNL TAKDVGSGTT NNSQACAQFL EQYFHNSDLT EFMRLFGGSF
260 270 280 290 300
THQASVAKVV GKQGRGRAGI EASLDVEYLM SAGANISTWV YSSPGRHEAQ
310 320 330 340 350
EPFLQWLLLL SNESSLPHVH TVSYGDDEDS LSSIYIQRVN TEFMKAAARG
360 370 380 390 400
LTLLFASGDT GAGCWSVSGR HKFRPSFPAS SPYVTTVGGT SFKNPFLITD
410 420 430 440 450
EVVDYISGGG FSNVFPRPPY QEEAVAQFLK SSSHLPPSSY FNASGRAYPD
460 470 480 490 500
VAALSDGYWV VSNMVPIPWV SGTSASTPVF GGILSLINEH RILNGRPPLG
510 520 530 540 550
FLNPRLYQQH GTGLFDVTHG CHESCLNEEV EGQGFCSGPG WDPVTGWGTP
560
NFPALLKTLL NP
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A1B0GRZ6 | A0A1B0GRZ6_MOUSE | Tripeptidyl-peptidase 1 | Tpp1 | 39 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 1 | M → V (PubMed:9989590).Curated | 1 | |
Sequence conflicti | 562 | P → LDPFVP (PubMed:9989590).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ011912 mRNA Translation: CAA09863.1 Different initiation. AF124599 Genomic DNA Translation: AAD32573.1 AF111172 mRNA Translation: AAD03083.1 AK002418 mRNA Translation: BAB22085.1 AK048279 mRNA Translation: BAC33293.1 AK170781 mRNA Translation: BAE42026.1 BC024820 mRNA Translation: AAH24820.1 |
CCDSi | CCDS21661.1 |
RefSeqi | NP_034036.1, NM_009906.6 |
Genome annotation databases
Ensembli | ENSMUST00000033184; ENSMUSP00000033184; ENSMUSG00000030894 |
GeneIDi | 12751 |
KEGGi | mmu:12751 |
UCSCi | uc009izg.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ011912 mRNA Translation: CAA09863.1 Different initiation. AF124599 Genomic DNA Translation: AAD32573.1 AF111172 mRNA Translation: AAD03083.1 AK002418 mRNA Translation: BAB22085.1 AK048279 mRNA Translation: BAC33293.1 AK170781 mRNA Translation: BAE42026.1 BC024820 mRNA Translation: AAH24820.1 |
CCDSi | CCDS21661.1 |
RefSeqi | NP_034036.1, NM_009906.6 |
3D structure databases
AlphaFoldDBi | O89023 |
SMRi | O89023 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 198754, 5 interactors |
IntActi | O89023, 1 interactor |
MINTi | O89023 |
STRINGi | 10090.ENSMUSP00000033184 |
Protein family/group databases
MEROPSi | S53.003 |
PTM databases
GlyConnecti | 2800, 9 N-Linked glycans (3 sites) |
GlyGeni | O89023, 5 sites, 9 N-linked glycans (3 sites) |
iPTMneti | O89023 |
PhosphoSitePlusi | O89023 |
Proteomic databases
EPDi | O89023 |
jPOSTi | O89023 |
MaxQBi | O89023 |
PaxDbi | O89023 |
PeptideAtlasi | O89023 |
PRIDEi | O89023 |
ProteomicsDBi | 259169 |
Protocols and materials databases
Antibodypediai | 23932, 430 antibodies from 39 providers |
DNASUi | 12751 |
Genome annotation databases
Ensembli | ENSMUST00000033184; ENSMUSP00000033184; ENSMUSG00000030894 |
GeneIDi | 12751 |
KEGGi | mmu:12751 |
UCSCi | uc009izg.1, mouse |
Organism-specific databases
CTDi | 1200 |
MGIi | MGI:1336194, Tpp1 |
VEuPathDBi | HostDB:ENSMUSG00000030894 |
Phylogenomic databases
eggNOGi | ENOG502QR6D, Eukaryota |
GeneTreei | ENSGT00390000008684 |
HOGENOMi | CLU_013783_5_1_1 |
InParanoidi | O89023 |
OMAi | HDEMKRM |
OrthoDBi | 1294880at2759 |
PhylomeDBi | O89023 |
TreeFami | TF333497 |
Enzyme and pathway databases
BRENDAi | 3.4.14.9, 3474 |
Miscellaneous databases
BioGRID-ORCSi | 12751, 2 hits in 74 CRISPR screens |
ChiTaRSi | Tpp1, mouse |
PROi | PR:O89023 |
RNActi | O89023, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000030894, Expressed in ileum and 313 other tissues |
Genevisiblei | O89023, MM |
Family and domain databases
CDDi | cd04056, Peptidases_S53, 1 hit cd11377, Pro-peptidase_S53, 1 hit |
Gene3Di | 3.40.50.200, 1 hit |
InterProi | View protein in InterPro IPR036852, Peptidase_S8/S53_dom_sf IPR015366, S53_propep IPR030400, Sedolisin_dom |
Pfami | View protein in Pfam PF09286, Pro-kuma_activ, 1 hit |
SMARTi | View protein in SMART SM00944, Pro-kuma_activ, 1 hit |
SUPFAMi | SSF52743, SSF52743, 1 hit |
PROSITEi | View protein in PROSITE PS51695, SEDOLISIN, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TPP1_MOUSE | |
Accessioni | O89023Primary (citable) accession number: O89023 Secondary accession number(s): Q543Q8, Q9QUS7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 15, 1998 |
Last sequence update: | December 1, 2000 | |
Last modified: | May 25, 2022 | |
This is version 166 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot