ERAP1

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ERAP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesERAP1, A-LAP, ALAP, APPILS, ARTS-1, ARTS1, ERAAP, ERAAP1, PILS-AP, PILSAP, endoplasmic reticulum aminopeptidase 1
External IDsOMIM: 606832 MGI: 1933403 HomoloGene: 140581 GeneCards: ERAP1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001040458
NM_001198541
NM_016442
NM_001349244

NM_030711

RefSeq (protein)

NP_001035548
NP_001185470
NP_057526
NP_001336173

NP_109636

Location (UCSC)Chr 5: 96.76 – 96.81 MbChr 13: 74.79 – 74.84 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator, also known as endoplasmic reticulum aminopeptidase 1 (ARTS-1), is a protein which in humans is encoded by the ARTS-1 gene.[5]

Endoplasmic reticulum amino peptidase 1 is active in the endoplasmic reticulum, which is involved in protein processing and transport. This protein is an aminopeptidase, which is an enzyme that cleaves peptides at the N-terminal into smaller fragments called amino acids.

Nomenclature

ARTS1 is also known as:

  • ER aminopeptidase 1 (ERAP1) the name accepted by the Hugo Gene Nomenclature Committee[6]
  • ER aminopeptidase associated with antigen processing (ERAAP) in mice [7]
  • Adipocyte-derived leucine aminopeptidase (ALAP)
  • Puromycin-insensitive leucine aminopeptidase (PILS-AP)

Function

ERAP1 has two major functions in the immune system:

  • First, ERAP1 cleaves several proteins called cytokine receptors on the surface of cells. Cleaving these receptors reduces their ability to transmit chemical signals into the cell, which affects the process of inflammation.
  • Second, ERAP1 trims peptides within the endoplasmic reticulum so that they can be loaded onto major histocompatibility complex (MHC) class I. These peptides are attached to MHC class I in the endoplasmic reticulum and exported to the cell surface, where they are displayed to the immune system. If the immune system recognizes the peptides as foreign (such as viral or bacterial peptides), it responds by triggering the infected cell to self-destruct.[8]

ARTS-1 is a member of the M1 family of zinc metallopeptidases which acts as an aminopeptidase that degrades oligopeptides by cleavage starting at the amino terminus. One of the functions of aminopeptidases is to degrade potentially toxic peptides in the cytosol.[5]

ARTS-1 is a transmembrane protein[citation needed] that is localized to the endoplasmic reticulum. It has been implicated in the following functions:

Clinical significance

Aminopeptidases play a role in the metabolism of several peptides that may be involved in blood pressure and the pathogenesis of essential hypertension.[5] Mutations in the ARTS-1 have been linked to an increased risk of ankylosing spondylitis but only in HLA-B27 positive patients.[10]

The protein encoded by this gene is an aminopeptidase involved in trimming HLA class I-binding precursors so that they can be presented on MHC class I molecules. The encoded protein acts as a monomer or as a heterodimer with ERAP2. This protein may also be involved in blood pressure regulation by inactivation of angiotensin II. Three transcript variants encoding two different isoforms have been found for this gene.[5]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000164307 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021583 - 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.
  5. ^ a b c d EntrezGene 51752
  6. ^ "HGNC". HGNC. Archived from the original on 11 April 2015. Retrieved 27 March 2014.
  7. ^ Serwold T, Gonzalez F, Kim J, Jacob R, Shastri N (2002). "ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum". Nature. 419 (6906): 480–3. doi:10.1038/nature01074. PMID 12368856. S2CID 4379291.
  8. ^ "ERAP1 - endoplasmic reticulum aminopeptidase 1 - Genetics Home Reference".
  9. ^ Goto Y, Ogawa K, Hattori A, Tsujimoto M (June 2011). "Secretion of endoplasmic reticulum aminopeptidase 1 is involved in the activation of macrophages induced by lipopolysaccharide and interferon-gamma". The Journal of Biological Chemistry. 286 (24): 21906–14. doi:10.1074/jbc.M111.239111. PMC 3122245. PMID 21531727.
  10. ^ Brionez TF, Reveille JD (2008). "The contribution of genes outside the major histocompatibility complex to susceptibility to ankylosing spondylitis". Current Opinion in Rheumatology. 20 (4): 384–91. doi:10.1097/BOR.0b013e32830460fe. PMID 18525349. S2CID 205485848.

External links

Further reading