Tpp1 tripeptidyl peptidase I [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Tpp1provided by MGI
Official Full Name: tripeptidyl peptidase Iprovided by MGI
Primary source: MGI:MGI:1336194
See related: Ensembl:ENSMUSG00000030894 AllianceGenome:MGI:1336194
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Cln2; LPIC; TPP-1; TPP-I
Summary: This gene encodes a lysosomal serine protease that cleaves N-terminal tripeptides from protein substrates. The encoded preproprotein undergoes autocatalytic processing to generate a mature enzyme. Mice lacking the encoded protein exhibit a progressive neurodegeneration and a greatly shortened lifespan. At the cellular level, mice lacking the encoded protein exhibit accumulation of autofluorescent lipopigments. Mutations in the human ortholog of this gene cause classical late-infantile neuronal ceroid lipofuscinosis. [provided by RefSeq, Nov 2015]
Expression: Ubiquitous expression in kidney adult (RPKM 66.4), subcutaneous fat pad adult (RPKM 41.2) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 7 E3; 7 55.97 cM

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	7	NC_000073.7 (105394018..105401489, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	7	NC_000073.6 (105744811..105752282, complement)

Chromosome 7 - NC_000073.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A mouse mutant deficient in both neuronal ceroid lipofuscinosis-associated proteins CLN3 and TPP1.
Title: A mouse mutant deficient in both neuronal ceroid lipofuscinosis-associated proteins CLN3 and TPP1.
Rssults suggested that CLN2, CLN3 and CLN5 genes may play an important role in early embryonal neurogenesis.
Title: Neuronal ceroid lipofuscinosis genes, CLN2, CLN3 and CLN5 are spatially and temporally co-expressed in a developing mouse brain.
Gemfibrozil and fenofibrate, Food and Drug Administration-approved lipid-lowering drugs, up-regulate tripeptidyl-peptidase 1 in brain cells via peroxisome proliferator-activated receptor alpha and may have implications in late infantile Batten disease therapy
Title: Gemfibrozil and fenofibrate, Food and Drug Administration-approved lipid-lowering drugs, up-regulate tripeptidyl-peptidase 1 in brain cells via peroxisome proliferator-activated receptor α: implications for late infantile Batten disease therapy.
TPPI activity becomes crucial for the neuronal functions later in development.
Title: Developmental study of tripeptidyl peptidase I activity in the mouse central nervous system and peripheral organs.
Results indicate that the loss of TPPI cannot be functionally compensated for by DPPI.
Title: Dipeptidyl-peptidase I does not functionally compensate for the loss of tripeptidyl-peptidase I in the neurodegenerative disease late-infantile neuronal ceroid lipofuscinosis.
While all treatment groups show a marked increase in total TPP-I activity over wild-type mice, neonatally treated mice displayed high levels of TPP-I activity in the CNS 1 yr after administration which was spread throughout the brain.
Title: Survival advantage of neonatal CNS gene transfer for late infantile neuronal ceroid lipofuscinosis.
Expression of 6% of normal TPPI activity increased lifespan to that of unaffected mice.
Title: Residual levels of tripeptidyl-peptidase I activity dramatically ameliorate disease in late-infantile neuronal ceroid lipofuscinosis.
TPP-I is the predominant proteolytic enzyme responsible for the intracellular degradation of neuromedin B
Title: The lysosomal degradation of neuromedin B is dependent on tripeptidyl peptidase-I: evidence for the impairment of neuropeptide degradation in late-infantile neuronal ceroid lipofuscinosis.
The CLN2-targeted mouse recapitulates much of the pathology and clinical features of classical late-infantile neuronal ceroid lipofuscinosis
Title: A mouse model of classical late-infantile neuronal ceroid lipofuscinosis based on targeted disruption of the CLN2 gene results in a loss of tripeptidyl-peptidase I activity and progressive neurodegeneration.
Lysosomal degradation of cholecystokinin-(29-33)-amide in mouse brain is dependent on this enzyme: implications for the degradation and storage of peptides in classical late-infantile neuronal ceroid lipofuscinosis (tripeptidyl peptidase-I)
Title: Lysosomal degradation of cholecystokinin-(29-33)-amide in mouse brain is dependent on tripeptidyl peptidase-I: implications for the degradation and storage of peptides in classical late-infantile neuronal ceroid lipofuscinosis.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (1)
Endonuclease-mediated (3)
Targeted (4) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D7Mit95 (e-PCR), detects polymorphism
- UniSTS:116736

Cln2 (e-PCR), detects polymorphism
- UniSTS:141353

AI414982 (e-PCR)
- UniSTS:208169

AW107731 (e-PCR)
- UniSTS:208175

PCDH16_1801 (e-PCR)
- UniSTS:280891

fl05f06.x1 (e-PCR)
- UniSTS:201902

UniSTS:496054 (e-PCR)
- UniSTS:496054

Tpp1 (e-PCR), detects polymorphism
- UniSTS:496054

D1Bda72 (e-PCR)
- UniSTS:239823

fk56e12.x1 (e-PCR)
- UniSTS:201209

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables endopeptidase activity	ISO Inferred from Sequence Orthology more info
enables endopeptidase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables lysophosphatidic acid binding	ISO Inferred from Sequence Orthology more info
enables lysophosphatidic acid binding	ISS Inferred from Sequence or Structural Similarity more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables peptidase activity	ISO Inferred from Sequence Orthology more info
enables peptidase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables peptide binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase activity	IEA Inferred from Electronic Annotation more info
enables serine-type peptidase activity	ISO Inferred from Sequence Orthology more info
enables serine-type peptidase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables sulfatide binding	ISO Inferred from Sequence Orthology more info
enables sulfatide binding	ISS Inferred from Sequence or Structural Similarity more info
enables tripeptidyl-peptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables tripeptidyl-peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables tripeptidyl-peptidase activity	ISO Inferred from Sequence Orthology more info
enables tripeptidyl-peptidase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed

Process	Evidence Code	Pubs
involved_in bone resorption	ISO Inferred from Sequence Orthology more info
involved_in bone resorption	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in central nervous system development	IBA Inferred from Biological aspect of Ancestor more info
involved_in epithelial cell differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within lysosomal protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within lysosome organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nervous system development	ISO Inferred from Sequence Orthology more info
involved_in nervous system development	ISS Inferred from Sequence or Structural Similarity more info	PubMed
acts_upstream_of_or_within neuromuscular process controlling balance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptide catabolic process	ISO Inferred from Sequence Orthology more info
involved_in peptide catabolic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in protein localization to chromosome, telomeric region	IEA Inferred from Electronic Annotation more info
involved_in protein localization to chromosome, telomeric region	ISO Inferred from Sequence Orthology more info
involved_in proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis	ISO Inferred from Sequence Orthology more info
involved_in proteolysis	ISS Inferred from Sequence or Structural Similarity more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in Golgi apparatus	ISS Inferred from Sequence or Structural Similarity more info
located_in lysosome	IDA Inferred from Direct Assay more info	PubMed
located_in lysosome	ISO Inferred from Sequence Orthology more info
located_in lysosome	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in melanosome	IEA Inferred from Electronic Annotation more info
located_in membrane raft	ISO Inferred from Sequence Orthology more info
located_in membrane raft	ISS Inferred from Sequence or Structural Similarity more info
located_in mitochondrion	HDA more info	PubMed
located_in recycling endosome	ISO Inferred from Sequence Orthology more info
located_in recycling endosome	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: tripeptidyl-peptidase 1

Names: ceroid-lipofuscinosis, neuronal 2; lysosomal pepstatin-insensitive protease; tripeptidyl aminopeptidase

NP_034036.1

EC 3.4.14.9

XP_011239970.1

EC 3.4.14.9

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_009906.6 → NP_034036.1 tripeptidyl-peptidase 1 preproprotein

See identical proteins and their annotated locations for NP_034036.1

Status: REVIEWED

Source sequence(s)

AA499658, AC121823, AK002418, AK048279

Consensus CDS

CCDS21661.1

UniProtKB/Swiss-Prot

O89023, Q543Q8, Q9QUS7

UniProtKB/TrEMBL

Q3TDY6, Q3U2Z6

Related

ENSMUSP00000033184.5, ENSMUST00000033184.6

Conserved Domains (2) summary

cd04056
Location:198 → 556

Peptidases_S53; Peptidase domain in the S53 family

cd11377
Location:34 → 173

Pro-peptidase_S53; Activation domain of S53 peptidases

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000073.7 Reference GRCm39 C57BL/6J

Range

105394018..105401489 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011241668.4 → XP_011239970.1 tripeptidyl-peptidase 1 isoform X1

See identical proteins and their annotated locations for XP_011239970.1

UniProtKB/TrEMBL

Q3TDY6, Q3U2Z6

Conserved Domains (2) summary

cd04056
Location:198 → 474

Peptidases_S53; Peptidase domain in the S53 family

cd11377
Location:34 → 173

Pro-peptidase_S53; Activation domain of S53 peptidases