Biology:Tripeptidyl peptidase II
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Tripeptidyl-peptidase 2 is an enzyme that in humans is encoded by the TPP2 gene.[1][2] Among other things it is heavily implicated in MHC (HLA) class-I processing, as it has both endopeptidase and exopeptidase activity.[3]
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.[4][5] Some genetic variants may result in a milder disease with sterile brain inflammation mimicking multiple sclerosis.[6] These observations underline the fundamental role of TPP2 in cells of the immune system.
References
- ↑ "Characterization of cDNA for human tripeptidyl peptidase II: the N-terminal part of the enzyme is similar to subtilisin". Biochemistry 30 (1): 168–174. January 1991. doi:10.1021/bi00215a025. PMID 1670990.
- ↑ "Entrez Gene: TPP2 tripeptidyl peptidase II". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7174.
- ↑ "A major role for TPPII in trimming proteasomal degradation products for MHC class I antigen presentation". Immunity 20 (4): 495–506. April 2004. doi:10.1016/S1074-7613(04)00074-3. PMID 15084277.
- ↑ "Dual proteolytic pathways govern glycolysis and immune competence". Cell 159 (7): 1578–1590. December 2014. doi:10.1016/j.cell.2014.12.001. PMID 25525876.
- ↑ "Immune deficiency, autoimmune disease and intellectual disability: A pleiotropic disorder caused by biallelic variants in the TPP2 gene". Clinical Genetics 99 (6): 780–788. June 2021. doi:10.1111/cge.13942. PMID 33586135.
- ↑ "TPP2 mutation associated with sterile brain inflammation mimicking MS". Neurology. Genetics 4 (6): e285. December 2018. doi:10.1212/NXG.0000000000000285. PMID 30533531.
External links
Further reading
- "Immunological cross-reactivity between human tripeptidyl peptidase II and fibronectin". The Biochemical Journal 267 (1): 149–154. April 1990. doi:10.1042/bj2670149. PMID 1691635.
- "Nucleotide sequence of cDNA covering the N-terminus of human tripeptidyl peptidase II". Biomedica Biochimica Acta 50 (4–6): 727–729. 1992. PMID 1840501.
- "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. November 1987. doi:10.1073/pnas.84.21.7508. PMID 3313395. Bibcode: 1987PNAS...84.7508T.
- "Purification and characterization of tripeptidylpeptidase-II from post-mortem human brain". Neurochemical Research 18 (7): 743–749. July 1993. doi:10.1007/BF00966768. PMID 8396212.
- "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. August 1993. doi:10.1006/geno.1993.1353. PMID 8406500.
- "Characterization and inhibition of a cholecystokinin-inactivating serine peptidase". Nature 380 (6573): 403–409. April 1996. doi:10.1038/380403a0. PMID 8602240. Bibcode: 1996Natur.380..403R.
- "A giant protease with potential to substitute for some functions of the proteasome". Science 283 (5404): 978–981. February 1999. doi:10.1126/science.283.5404.978. PMID 9974389.
- "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. February 2000. doi:10.1021/jm990226g. PMID 10691692.
- "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. October 2002. doi:10.4049/jimmunol.169.8.4161. PMID 12370345.
- "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. December 2002. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Identification and characterization of the promoter for the gene encoding human tripeptidyl-peptidase II". Gene 345 (2): 249–257. January 2005. doi:10.1016/j.gene.2004.11.042. PMID 15716107.
- "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. July 2006. doi:10.1016/j.bbrc.2006.05.141. PMID 16762321.
- "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. August 2006. doi:10.4049/jimmunol.177.3.1434. PMID 16849449.
- "Characterization of the promoter of the gene encoding human tripeptidyl-peptidase II and identification of upstream silencer elements". Gene 393 (1–2): 62–69. May 2007. doi:10.1016/j.gene.2007.01.015. PMID 17343995.
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