ERAP2

ERAP2
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 3SE6, 4E36, 4JBS, 5CU5, 5AB2, 5AB0
Identifiers
Aliases	ERAP2, L-RAP, LRAP, endoplasmic reticulum aminopeptidase 2
External IDs	OMIM: 609497; HomoloGene: 75183; GeneCards: ERAP2; OMA:ERAP2 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q15 Start 96,875,986 bp End 96,919,703 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell granulocyte lymph node superficial temporal artery visceral pleura epithelium of nasopharynx monocyte epithelium of colon appendix Achilles tendon n/a More reference expression data BioGPS n/a
Gene ontology Molecular function aminopeptidase activity metallopeptidase activity peptidase activity hydrolase activity zinc ion binding metal ion binding peptide binding metalloaminopeptidase activity endopeptidase activity Cellular component integral component of membrane endoplasmic reticulum lumen endoplasmic reticulum membrane membrane endoplasmic reticulum plasma membrane cytoplasm Biological process immune system process adaptive immune response proteolysis regulation of blood pressure antigen processing and presentation of peptide antigen via MHC class I peptide catabolic process antigen processing and presentation of endogenous peptide antigen via MHC class I signal transduction cell-cell signaling Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 64167 n/a Ensembl ENSG00000164308 n/a UniProt Q6P179 n/a RefSeq (mRNA) NM_001130140 NM_022350 NM_001329229 NM_001329233 n/a RefSeq (protein) NP_001123612 NP_001316158 NP_001316162 NP_071745 n/a Location (UCSC) Chr 5: 96.88 – 96.92 Mb n/a PubMed search n/a
Wikidata
View/Edit Human

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.

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.

Genetics

Mutations in the ERAP2 gene 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. However this version of the gene also increases the risk of Crohn’s disease.

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.

See also

• Major histocompatibility complex (MHC)
• Tripeptidyl peptidase

Further reading

• Xu XR, Huang J, Xu ZG, Qian BZ, Zhu ZD, Yan Q, et al. (December 2001). "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. Bibcode:2001PNAS...9815089X. doi:10.1073/pnas.241522398. PMC 64988. PMID 11752456.
• Hill LD, Hilliard DD, York TP, Srinivas S, Kusanovic JP, Gomez R, et al. (May 2011). "Fetal ERAP2 variation is associated with preeclampsia in African Americans in a case-control study". BMC Medical Genetics. 12: 64. doi:10.1186/1471-2350-12-64. PMC 3103419. PMID 21569342.
• Ascher DB, Polekhina G, Parker MW (April 2012). "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. doi:10.1107/S1744309112006963. PMC 3325822. PMID 22505422.
• Kamphausen E, Kellert C, Abbas T, Akkad N, Tenzer S, Pawelec G, et al. (August 2010). "Distinct molecular mechanisms leading to deficient expression of ER-resident aminopeptidases in melanoma". Cancer Immunology, Immunotherapy. 59 (8): 1273–1284. doi:10.1007/s00262-010-0856-7. PMC 11030553. PMID 20419298. S2CID 24302488.
• Stratikos E, Stern LJ (October 2013). "Antigenic peptide trimming by ER aminopeptidases--insights from structural studies". Molecular Immunology. 55 (3–4): 212–219. doi:10.1016/j.molimm.2013.03.002. PMC 3657621. PMID 23545452.
• Bjornsson HT, Albert TJ, Ladd-Acosta CM, Green RD, Rongione MA, Middle CM, et al. (May 2008). "SNP-specific array-based allele-specific expression analysis". Genome Research. 18 (5): 771–779. doi:10.1101/gr.073254.107. PMC 2336807. PMID 18369178.
• Mason CC, Hanson RL, Ossowski V, Bian L, Baier LJ, Krakoff J, Bogardus C (February 2011). "Bimodal distribution of RNA expression levels in human skeletal muscle tissue". BMC Genomics. 12: 98. doi:10.1186/1471-2164-12-98. PMC 3044673. PMID 21299892.
• Haroon N, Tsui FW, Chiu B, Tsui HW, Inman RD (September 2010). "Serum cytokine receptors in ankylosing spondylitis: relationship to inflammatory markers and endoplasmic reticulum aminopeptidase polymorphisms". The Journal of Rheumatology. 37 (9): 1907–1910. doi:10.3899/jrheum.100019. PMID 20595269. S2CID 27707315.
• Qu HQ, Marchand L, Fréchette R, Bacot F, Lu Y, Polychronakos C (March 2007). "No association of type 1 diabetes with a functional polymorphism of the LRAP gene". Molecular Immunology. 44 (8): 2135–2138. 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.