TPP2 (Tripeptidyl Peptidase 2)
A serine exopeptidase involved in protein degradation, antigen processing, and linked to neurodevelopmental disorders and cancer.
Gene Information Card
| Symbol | TPP2 |
|---|---|
| Full Name | Tripeptidyl Peptidase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 13q32.3 |
| NCBI Gene ID | 7157 ncbi.nlm.nih.gov/gene/7157 |
| Ensembl ID | ENSG00000134900 |
| UniProt ID | P29144 |
| OMIM ID | 190470 |
| HGNC ID | 12016 |
| Aliases | TPP-II, TPP-2, TPPII |
Description
TPP2 encodes tripeptidyl peptidase 2, a cytosolic serine exopeptidase that cleaves N-terminal tripeptides from longer peptides. It plays a key role in intracellular protein degradation downstream of the proteasome and in antigen processing for MHC class I presentation. Mutations in TPP2 are associated with autosomal recessive neurodevelopmental disorders and altered immune function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with microcephaly and spasticity (NEDMIS) | Loss-of-function mutations impair peptide processing, leading to neuronal dysfunction. | OMIM #617113; PMID: 26063658 |
| Autoimmune lymphoproliferative syndrome (ALPS-like) | Defective TPP2 disrupts T-cell homeostasis and apoptosis. | PMID: 25666262 |
| Colorectal cancer | Overexpression of TPP2 promotes tumor growth and immune evasion. | COSMIC; PMID: 23966116 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Lymph node | 22.8 | High |
| Liver | 10.5 | Medium |
| Testis | 8.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.4 | Embryonic kidney |
| K562 | 25.1 | Leukemia |
| HepG2 | 12.7 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1303C>T (p.Arg435*) | Nonsense | Rare | Loss of function |
| c.1685G>A (p.Arg562Gln) | Missense | Rare | Reduced enzymatic activity |
| c.2242C>T (p.Arg748Trp) | Missense | Rare | Dominant-negative effect suspected |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated protein or nonsense-mediated decay.
Gain of Function (GOF)
Not well documented; overexpression in some cancers may confer gain-of-function.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg748Trp) that disrupt oligomerization and reduce wild-type activity.
View complete mutation data：
Gene Ontology (GO)
| • serine-type exopeptidase activity | • tripeptidyl-peptidase activity |
| • proteolysis | • antigen processing and presentation of endogenous peptide antigen via MHC class I |
| • cytosol | • cytoplasm |
Pathways
• Antigen processing and presentation (KEGG hsa04612)
• Proteasome degradation (Reactome R-HSA-983168)
Protein Summary
TPP2 is a 1249-amino-acid serine protease that forms large homo-oligomeric complexes. It removes tripeptides from the N-terminus of peptides generated by the proteasome, contributing to final protein breakdown and generation of antigenic peptides. Its activity is regulated by substrate availability and cellular stress.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TPP2 Knockout HEK293 Cell Line | EDJ-KQ2743 | Human | 7174 | Details Get a Quote |
| TPP2 Knockout HCT 116 Cell Line | EDJ-KQ22252 | Human | 7174 | Details Get a Quote |
| TPP2 Knockout A-549 Cell Line | EDJ-KQ23623 | Human | 7174 | Details Get a Quote |
| TPP2 Knockout HeLa Cell Line | EDJ-KQ23624 | Human | 7174 | Details Get a Quote |
