Biology:ERAP2
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Endoplasmic reticulum aminopeptidase 2 is an aminopeptidase in humans involved in antigen presentation. It is encoded by the ERAP2 gene.
Function
ERAP1 and ERAP2 are Aminopeptidases, able to trim precursors to antigenic peptides in the endoplasmic reticulum. They hydrolyze N-terminal amino acids of proteins or peptide substrates so the Major histocompatibility complex (MHC) class I can present them to CD8+ T cells.[1]
ERAP2 plays a central role in antigen presentation and impacts the response of at least 4 cytokines: It is positively correlated with CCL3, which is involved in the recruitment of neutrophils upon infection, whereas it is inversely correlated with granulocyte colony-stimulating factor , interleukin-1β and IL-10.[2]
Genetics
Mutations in the ERAP2 gene[3] were found in DNA extracts derived from the skeletons of people who died shortly before, during or soon after the Black Death 1348 in three London cemeteries, including East Smithfield plague cemetery and from Denmark. Per this study, carrying two protective versions of ERAP2 made people 40 percent likelier to survive a Yersinia pestis infection.[2] However this version of the gene also increases the risk of Crohn’s disease.[4]
There is evidence that the Black Death shaped genetic diversity in Europe, in that people who had protective variant of the ERAP2 gene were much more likely to survive Yersinia pestis infection, the causitive agent of Black Death.[5]
See also
References
- ↑ "Human leukocyte-derived arginine aminopeptidase. The third member of the oxytocinase subfamily of aminopeptidases". The Journal of Biological Chemistry 278 (34): 32275–32283. August 2003. doi:10.1074/jbc.M305076200. PMID 12799365.
- ↑ 2.0 2.1 "Evolution of immune genes is associated with the Black Death". Nature 611 (7935): 312–319. October 2022. doi:10.1038/s41586-022-05349-x. PMID 36261521. Bibcode: 2022Natur.611..312K.
- ↑ "Entrez Gene: Endoplasmic reticulum amino peptidase 2". https://www.ncbi.nlm.nih.gov/gene/64167.
- ↑ "How the 'Black Death' Left Its Genetic Mark on Future Generations" (in en-US). The New York Times. 2022-10-19. ISSN 0362-4331. https://www.nytimes.com/2022/10/19/science/bubonic-plague-black-death-genetic-protection.html.
- ↑ "Evolution of immune genes is associated with the Black Death". Nature 611 (7935): 312–319. November 2022. doi:10.1038/s41586-022-05349-x. PMID 36261521. Bibcode: 2022Natur.611..312K.
Further reading
- "Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver". Proceedings of the National Academy of Sciences of the United States of America 98 (26): 15089–15094. December 2001. doi:10.1073/pnas.241522398. PMID 11752456. Bibcode: 2001PNAS...9815089X.
- "Fetal ERAP2 variation is associated with preeclampsia in African Americans in a case-control study". BMC Medical Genetics 12: 64. May 2011. doi:10.1186/1471-2350-12-64. PMID 21569342.
- "Crystallization and preliminary X-ray diffraction analysis of human endoplasmic reticulum aminopeptidase 2". Acta Crystallographica. Section F, Structural Biology and Crystallization Communications 68 (Pt 4): 468–471. April 2012. doi:10.1107/S1744309112006963. PMID 22505422.
- "Distinct molecular mechanisms leading to deficient expression of ER-resident aminopeptidases in melanoma". Cancer Immunology, Immunotherapy 59 (8): 1273–1284. August 2010. doi:10.1007/s00262-010-0856-7. PMID 20419298.
- "Antigenic peptide trimming by ER aminopeptidases--insights from structural studies". Molecular Immunology 55 (3–4): 212–219. October 2013. doi:10.1016/j.molimm.2013.03.002. PMID 23545452.
- "SNP-specific array-based allele-specific expression analysis". Genome Research 18 (5): 771–779. May 2008. doi:10.1101/gr.073254.107. PMID 18369178.
- "Bimodal distribution of RNA expression levels in human skeletal muscle tissue". BMC Genomics 12: 98. February 2011. doi:10.1186/1471-2164-12-98. PMID 21299892.
- "Serum cytokine receptors in ankylosing spondylitis: relationship to inflammatory markers and endoplasmic reticulum aminopeptidase polymorphisms". The Journal of Rheumatology 37 (9): 1907–1910. September 2010. doi:10.3899/jrheum.100019. PMID 20595269.
- "No association of type 1 diabetes with a functional polymorphism of the LRAP gene". Molecular Immunology 44 (8): 2135–2138. March 2007. doi:10.1016/j.molimm.2006.10.015. PMID 17129607.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
![]() | Original source: https://en.wikipedia.org/wiki/ERAP2.
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