Tpp2 tripeptidyl peptidase II [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Tpp2provided by MGI
Official Full Name: tripeptidyl peptidase IIprovided by MGI
Primary source: MGI:MGI:102724
See related: Ensembl:ENSMUSG00000041763 AllianceGenome:MGI:102724
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: TPP-2; TppII
Summary: Predicted to enable exopeptidase activity; identical protein binding activity; and peptide binding activity. Predicted to be involved in intracellular amino acid homeostasis and protein catabolic process. Predicted to be located in nuclear body. Predicted to be active in cytosol. Human ortholog(s) of this gene implicated in primary immunodeficiency disease. Orthologous to human TPP2 (tripeptidyl peptidase 2). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Ubiquitous expression in testis adult (RPKM 13.0), placenta adult (RPKM 12.4) and 27 other tissues See more
Orthologs: human all
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Genomic context

Location:: 1 C1.1; 1 23.5 cM

Exon count:: 30

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (43973130..44042160)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (43933970..44003000)

Chromosome 1 - NC_000067.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

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?

Tripeptidyl peptidase II coordinates the homeostasis of calcium and lipids in the central nervous system and its depletion causes presenile dementia in female mice through calcium/lipid dyshomeostasis-induced autophagic degradation of CYP19A1.
Title: Tripeptidyl peptidase II coordinates the homeostasis of calcium and lipids in the central nervous system and its depletion causes presenile dementia in female mice through calcium/lipid dyshomeostasis-induced autophagic degradation of CYP19A1.
Data indicate that TPPII can regulate sperm maturation by modulating intracellular Ca(2+) stores via the type 3 RyR.
Title: Tripeptidyl peptidase II regulates sperm function by modulating intracellular Ca(2+) stores via the ryanodine receptor.
Previously unknown differences between TPP II orthologues and subtilisin as well as features that might be conserved within the entire family of subtilisin-like serine peptidases.
Title: Exploring the active site of tripeptidyl-peptidase II through studies of pH dependence of reaction kinetics.
These data indicate that while TPPII contributes to the trimming of peptides with very long N-terminal extensions, TPPII is not essential for generating most MHC class I-presented peptides or for stimulating CTL responses to several Ags in vivo.
Title: Analysis of the role of tripeptidyl peptidase II in MHC class I antigen presentation in vivo.
These results do not support a generally important role of TPPII for viability and proliferation of transformed cells or their p53-mediated DNA damage response.
Title: Viability and DNA damage responses of TPPII-deficient Myc- and Ras-transformed fibroblasts.
Data show that mice that were homozygous for an insertion in the Tpp2 locus were embryonic lethal and Tpp2 heterozygous mutants were lean compared with wild-type littermates, although food intake was normal.
Title: Tripeptidyl peptidase II promotes fat formation in a conserved fashion.
TPPII is important for maintaining normal cellular and systemic physiology, which may be relevant for potential therapeutic applications of TPPII inhibitors
Title: Activation of cellular death programs associated with immunosenescence-like phenotype in TPPII knockout mice.
The data suggest a moderate, predominantly destructive role of TPPII in class I Ag processing.
Title: Analysis of direct and cross-presentation of antigens in TPPII knockout mice.
Tripeptidyl peptidase II is crucial for nucleoprotein epitope generation during major histocompatibility complex class I complex viral antigen processing both in the presence and absence of lactacystin-sensitive proteasome action.
Title: Need for tripeptidyl-peptidase II in major histocompatibility complex class I viral antigen processing when proteasomes are detrimental.
TPPII is not generally required for the production of major histocompatibility class I-restricted peptides, but presentation of some peptides can be negatively affected by TPPII.
Title: No essential role for tripeptidyl peptidase II for the processing of LCMV-derived T cell epitopes.

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Variation

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Alleles

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

Endonuclease-mediated (4)
Gene trapped (2)
Targeted (2) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D10Mit157.2 (e-PCR), detects polymorphism
- UniSTS:126061

X81323 (e-PCR)
- UniSTS:125865

X81323 (e-PCR)
- UniSTS:163248

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables aminopeptidase activity	ISO Inferred from Sequence Orthology more info
enables aminopeptidase activity	ISS Inferred from Sequence or Structural Similarity more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables peptide binding	ISO Inferred from Sequence Orthology more info
enables serine-type endopeptidase activity	IEA Inferred from Electronic Annotation more info
enables tripeptidyl-peptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables tripeptidyl-peptidase activity	IEA Inferred from Electronic Annotation more info
enables tripeptidyl-peptidase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in intracellular amino acid homeostasis	ISO Inferred from Sequence Orthology more info
involved_in protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in nuclear body	IEA Inferred from Electronic Annotation more info
located_in nuclear body	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: tripeptidyl-peptidase 2

Names: TPP-II; tripeptidyl aminopeptidase

NP_001297469.1

EC 3.4.14.10

NP_033444.1

EC 3.4.14.10

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_001310540.1 → NP_001297469.1 tripeptidyl-peptidase 2 isoform 2

See identical proteins and their annotated locations for NP_001297469.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

BC060627, BY147762

Consensus CDS

CCDS78577.1

UniProtKB/TrEMBL

Q3TW28

Related

ENSMUSP00000139918.2, ENSMUST00000188313.7

Conserved Domains (3) summary

cd04857
Location:14 → 489

Peptidases_S8_Tripeptidyl_Aminopeptidase_II; Peptidase S8 family domain in Tripeptidyl aminopeptidases_II

pfam00082
Location:236 → 500

Peptidase_S8; Subtilase family

pfam12580
Location:777 → 960

TPPII; Tripeptidyl peptidase II
NM_009418.3 → NP_033444.1 tripeptidyl-peptidase 2 isoform 1

See identical proteins and their annotated locations for NP_033444.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

BB725588, BC060627, BY147762

Consensus CDS

CCDS14926.1

UniProtKB/Swiss-Prot

Q5D072, Q64514

UniProtKB/TrEMBL

Q3TW28

Related

ENSMUSP00000085244.4, ENSMUST00000087933.10

Conserved Domains (3) summary

cd04857
Location:14 → 489

Peptidases_S8_Tripeptidyl_Aminopeptidase_II; Peptidase S8 family domain in Tripeptidyl aminopeptidases_II

pfam00082
Location:236 → 500

Peptidase_S8; Subtilase family

pfam12580
Location:777 → 960

TPPII; Tripeptidyl peptidase II