Tripeptidyl peptidase II

TPP2
Identifiers
Aliases	TPP2 , TPP-2, TPPII, Tripeptidyl peptidase II, tripeptidyl peptidase 2, TPP-II, IMD78
External IDs	OMIM: 190470; MGI: 102724; HomoloGene: 2471; GeneCards: TPP2; OMA:TPP2 - orthologs
Gene location (Human) Chr. Chromosome 13 (human) [1] Band 13q33.1 Start 102,596,986 bp [1] End 102,679,958 bp [1]
Gene location (Mouse) Chr. Chromosome 1 (mouse) [2] Band 1 C1.1|1 23.5 cM Start 43,972,807 bp [2] End 44,042,160 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in left testis right testis sperm Achilles tendon epithelium of colon monocyte rectum testicle muscle of thigh right uterine tube Top expressed in spermatid spermatocyte seminiferous tubule tail of embryo esophagus mandibular prominence maxillary prominence atrioventricular valve gastrula Gonadal ridge More reference expression data BioGPS More reference expression data
Gene ontology Molecular function tripeptidyl-peptidase activity peptidase activity endopeptidase activity serine-type peptidase activity protein binding hydrolase activity aminopeptidase activity serine-type endopeptidase activity identical protein binding Cellular component nucleus nucleoplasm cytoplasm cytosol nuclear body Biological process protein polyubiquitination proteolysis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7174 22019 Ensembl ENSG00000134900 ENSMUSG00000041763 UniProt P29144 Q64514 RefSeq (mRNA) NM_003291 NM_001330588 NM_001367947 NM_009418 NM_001310540 RefSeq (protein) NP_001317517 NP_003282 NP_001354876 NP_001297469 NP_033444 Location (UCSC) Chr 13: 102.6 – 102.68 Mb Chr 1: 43.97 – 44.04 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Tripeptidyl-peptidase 2 is an enzyme that in humans is encoded by the TPP2 gene. ^{[5] [6]} Among other things it is heavily implicated in MHC (HLA) class-I processing, as it has both endopeptidase and exopeptidase activity. ^[7]

Clinical significance and genetic deficiency

Biallelic deleterious variants in the TPP2 gene may result in a recessive disorder with immune deficiency, autoimmune disease and intellectual disability. ^{[8] [9]} Some genetic variants may result in a milder disease with sterile brain inflammation mimicking multiple sclerosis. ^[10] These observations underline the fundamental role of TPP2 in cells of the immune system.

References

1. GRCh38: Ensembl release 89: ENSG00000134900 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000041763 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Tomkinson B, Jonsson AK (January 1991). "Characterization of cDNA for human tripeptidyl peptidase II: the N-terminal part of the enzyme is similar to subtilisin". Biochemistry. 30 (1): 168–174. doi:10.1021/bi00215a025. PMID   1670990.
6. "Entrez Gene: TPP2 tripeptidyl peptidase II".
7. Reits E, Neijssen J, Herberts C, Benckhuijsen W, Janssen L, Drijfhout JW, Neefjes J (April 2004). "A major role for TPPII in trimming proteasomal degradation products for MHC class I antigen presentation". Immunity. 20 (4): 495–506. doi: 10.1016/S1074-7613(04)00074-3 . PMID   15084277.
8. Lu W, Zhang Y, McDonald DO, Jing H, Carroll B, Robertson N, et al. (December 2014). "Dual proteolytic pathways govern glycolysis and immune competence". Cell. 159 (7): 1578–1590. doi:10.1016/j.cell.2014.12.001. PMC   4297473 . PMID   25525876.
9. Atallah I, Quinodoz M, Campos-Xavier B, Peter VG, Fouriki A, Bonvin C, et al. (June 2021). "Immune deficiency, autoimmune disease and intellectual disability: A pleiotropic disorder caused by biallelic variants in the TPP2 gene". Clinical Genetics. 99 (6): 780–788. doi:10.1111/cge.13942. PMID   33586135. S2CID   231926886.
10. Reinthaler EM, Graf E, Zrzavy T, Wieland T, Hotzy C, Kopecky C, et al. (December 2018). "TPP2 mutation associated with sterile brain inflammation mimicking MS". Neurology. Genetics. 4 (6): e285. doi:10.1212/NXG.0000000000000285. PMC   6244017 . PMID   30533531.

External links

• The MEROPS online database for peptidases and their inhibitors: S08.090

Further reading

• Tomkinson B, Zetterqvist O (April 1990). "Immunological cross-reactivity between human tripeptidyl peptidase II and fibronectin". The Biochemical Journal. 267 (1): 149–154. doi:10.1042/bj2670149. PMC   1131257 . PMID   1691635.
• Tomkinson B (1992). "Nucleotide sequence of cDNA covering the N-terminus of human tripeptidyl peptidase II". Biomedica Biochimica Acta. 50 (4–6): 727–729. PMID   1840501.
• Tomkinson B, Wernstedt C, Hellman U, Zetterqvist O (November 1987). "Active site of tripeptidyl peptidase II from human erythrocytes is of the subtilisin type". Proceedings of the National Academy of Sciences of the United States of America. 84 (21): 7508–7512. Bibcode:1987PNAS...84.7508T. doi: 10.1073/pnas.84.21.7508 . PMC   299325 . PMID   3313395.
• Wilson C, Gibson AM, McDermott JR (July 1993). "Purification and characterization of tripeptidylpeptidase-II from post-mortem human brain". Neurochemical Research. 18 (7): 743–749. doi:10.1007/BF00966768. PMID   8396212. S2CID   21957759.
• Martinsson T, Vujic M, Tomkinson B (August 1993). "Localization of the human tripeptidyl peptidase II gene (TPP2) to 13q32-q33 by nonradioactive in situ hybridization and somatic cell hybrids". Genomics. 17 (2): 493–495. doi:10.1006/geno.1993.1353. PMID   8406500.
• Rose C, Vargas F, Facchinetti P, Bourgeat P, Bambal RB, Bishop PB, et al. (April 1996). "Characterization and inhibition of a cholecystokinin-inactivating serine peptidase". Nature. 380 (6573): 403–409. Bibcode:1996Natur.380..403R. doi:10.1038/380403a0. PMID   8602240. S2CID   4269327.
• Geier E, Pfeifer G, Wilm M, Lucchiari-Hartz M, Baumeister W, Eichmann K, Niedermann G (February 1999). "A giant protease with potential to substitute for some functions of the proteasome". Science. 283 (5404): 978–981. doi:10.1126/science.283.5404.978. PMID   9974389.
• Ganellin CR, Bishop PB, Bambal RB, Chan SM, Law JK, Marabout B, et al. (February 2000). "Inhibitors of tripeptidyl peptidase II. 2. Generation of the first novel lead inhibitor of cholecystokinin-8-inactivating peptidase: a strategy for the design of peptidase inhibitors". Journal of Medicinal Chemistry. 43 (4): 664–674. doi:10.1021/jm990226g. PMID   10691692.
• Lévy F, Burri L, Morel S, Peitrequin AL, Lévy N, Bachi A, et al. (October 2002). "The final N-terminal trimming of a subaminoterminal proline-containing HLA class I-restricted antigenic peptide in the cytosol is mediated by two peptidases". Journal of Immunology. 169 (8): 4161–4171. doi: 10.4049/jimmunol.169.8.4161 . PMID   12370345.
• Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–16903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Lindås AC, Tomkinson B (January 2005). "Identification and characterization of the promoter for the gene encoding human tripeptidyl-peptidase II". Gene. 345 (2): 249–257. doi:10.1016/j.gene.2004.11.042. PMID   15716107.
• Stavropoulou V, Vasquez V, Cereser B, Freda E, Masucci MG (July 2006). "TPPII promotes genetic instability by allowing the escape from apoptosis of cells with activated mitotic checkpoints". Biochemical and Biophysical Research Communications. 346 (2): 415–425. doi:10.1016/j.bbrc.2006.05.141. PMID   16762321.
• York IA, Bhutani N, Zendzian S, Goldberg AL, Rock KL (August 2006). "Tripeptidyl peptidase II is the major peptidase needed to trim long antigenic precursors, but is not required for most MHC class I antigen presentation". Journal of Immunology. 177 (3): 1434–1443. doi: 10.4049/jimmunol.177.3.1434 . PMID   16849449.
• Lindås AC, Tomkinson B (May 2007). "Characterization of the promoter of the gene encoding human tripeptidyl-peptidase II and identification of upstream silencer elements". Gene. 393 (1–2): 62–69. doi:10.1016/j.gene.2007.01.015. PMID   17343995.