ERAP2

Protein-coding gene in the species Homo sapiens
ERAP2
Available structures
PDBHuman UniProt search: PDBe RCSB
List of PDB id codes

3SE6, 4E36, 4JBS, 5CU5, 5AB2, 5AB0

Identifiers
AliasesERAP2, L-RAP, LRAP, endoplasmic reticulum aminopeptidase 2
External IDsOMIM: 609497; HomoloGene: 75183; GeneCards: ERAP2; OMA:ERAP2 - orthologs
Gene location (Human)
Chromosome 5 (human)
Chr.Chromosome 5 (human)[1]
Chromosome 5 (human)
Genomic location for ERAP2
Genomic location for ERAP2
Band5q15Start96,875,986 bp[1]
End96,919,703 bp[1]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • lymph node

  • superficial temporal artery

  • visceral pleura

  • monocyte

  • appendix

  • Achilles tendon

  • spleen

  • blood

  • jejunal mucosa

  • palpebral conjunctiva
    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
SpeciesHumanMouse
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 Mbn/a
PubMed search[2]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.[3]

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.[4]

Genetics

Mutations in the ERAP2 gene[5] 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.[4] However this version of the gene also increases the risk of Crohn’s disease.[6]

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.[7]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000164308 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ Tanioka T, Hattori A, Masuda S, Nomura Y, Nakayama H, Mizutani S, Tsujimoto M (August 2003). "Human leukocyte-derived arginine aminopeptidase. The third member of the oxytocinase subfamily of aminopeptidases". The Journal of Biological Chemistry. 278 (34): 32275–32283. doi:10.1074/jbc.M305076200. PMID 12799365.
  4. ^ a b Klunk J, Vilgalys TP, Demeure CE, Cheng X, Shiratori M, Madej J, et al. (October 2022). "Evolution of immune genes is associated with the Black Death". Nature. 611 (7935): 312–319. Bibcode:2022Natur.611..312K. doi:10.1038/s41586-022-05349-x. PMC 9580435. PMID 36261521.
  5. ^ "Entrez Gene: Endoplasmic reticulum amino peptidase 2".
  6. ^ Zimmer C (2022-10-19). "How the 'Black Death' Left Its Genetic Mark on Future Generations". The New York Times. ISSN 0362-4331. Retrieved 2022-10-24.
  7. ^ Klunk J, Vilgalys TP, Demeure CE, Cheng X, Shiratori M, Madej J, et al. (November 2022). "Evolution of immune genes is associated with the Black Death". Nature. 611 (7935): 312–319. Bibcode:2022Natur.611..312K. doi:10.1038/s41586-022-05349-x. PMC 9580435. PMID 36261521.

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.

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