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)
End	102,679,958 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	44,042,160 bp
RNA expression pattern
	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
	; ;
	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
	7174
	22019
	ENSG00000134900
	ENSMUSG00000041763
	P29144
	Q64514
	NM_003291; NM_001330588; NM_001367947
	NM_009418; NM_001310540
	NP_001317517; NP_003282; NP_001354876
	NP_001297469; NP_033444
	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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000134900 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000041763 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ "Entrez Gene: TPP2 tripeptidyl peptidase II".
^ 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.
^ 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.
^ 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.
^ 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

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.

This article on a gene on human chromosome 13 is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000134900 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid1670990-5] 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.

[entrez-6] "Entrez Gene: TPP2 tripeptidyl peptidase II".

[pmid15084277-7] 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.

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v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

Clinical significance and genetic deficiency

References

External links

Further reading