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Search results 1 to 3 out of 3 for Erap1

Category restricted to ProteinDomain (x)

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Category: ProteinDomain
Type Details Score
Protein Domain
Type: Family
Description: Endoplasmic reticulum aminopeptidase 1 (ERAP1 or PILS; MEROPS identifier M01.018) is an aminopeptidase with a preference to release Leu or Met from the N terminus of a peptide, but can hydrolyze Phe, Tyr, Ile or Cys bonds but poorly [, ]. The aminopeptidase is insensitive to inhibition by puromycin (which inhibits cytosol alanyl aminopeptidase and dipeptidyl-peptidases II and IV) and is also known as puromycin-insensitive leucyl-specific aminopeptidase or PILS-AP [, ]. In humans, ERAP1 associates with another aminopeptidase, ERAP2, in the endoplasmic reticulum and both participate in the processing of MHC-presented peptides []. Peptides generated by degradation of proteins by the proteasome bind to a transporter associated with antigen presentation (TAP) and are exported across the plasma membrane from the cytoplasm to the endoplasmic reticulum where they are trimmed by the ERAP aminopeptidases and cystinyl aminopeptidase to be 8-11 amino acids in length which then associate with the MHC complex and beta2-microglobulin []. ERAP1 is most active with peptides 9-16 residues long, but activity drops once a peptide optimal for antigen presentation is achieved. This molecular ruler effect is achieved by binding the C terminus of the substrate peptide close to the active site []. ERAP1 may also function in blood pressure regulation because it cleaves angiotensin II to the tripeptide His-Pro-Phe via angiotensin II and IV intermediates, and converts kallidin to bradykinin []. ERAP1 has been associated with several human diseases, including ankylosing spondylitis [], psoriasis [], type 1 diabetes []and osteoporsis [].
Protein Domain
Type: Family
Description: The ERAP2 aminopeptidase (endoplasmic reticulum aminopeptidase 2; MEROPS identifier M01.024) releases an amino acid from the N terminus of a peptide or protein but is unable to cleave Xaa-Pro and Pro-Xaa bonds. Preferentially, arginyl bonds are hydrolysed most efficiantly, followed by lysyl bonds []. ERAP2 is localized to the endoplasmic reticulum of B lymphocytes []and epithelial components of non-lymphoid tissue.Human ERAP1 and 2 co-localize in breast, endometrium, epididymus and ovary, whereas ERAP2 only is found in kidney, gall bladder and urinary bladder []. ERAP2 is important for antigen presentation on the cell surface by the major histocompatabiity complex (MHC). The proteasome degrades cytoplasmic proteins and generates peptides. Some of these peptides are transported to the lumen of the endoplasmic reticulum by a transport associated with antigen presntation (TAP). Trimming at the amino terminus by the aminopeptidases ERAP1 and ERAP2 generates a peptide of the correct length which can then associate with the MHC [, ]. Polymorphisms of ERAP2 have been implicated in ankylosing spondylitis [], Crohn's disease []and pre-eclampsia [].
Protein Domain
Type: Family
Description: This M1 peptidase family includes eukaryotic and bacterial members: aminopeptidase N (APN; MEROPS identifier M01.001), aminopeptidase Q (APQ, laeverin; MEROPS identifier M01.026) [, ], endoplasmic reticulum aminopeptidase 1 (ERAP1; MEROPS identifier M01.018) []as well as tricorn interacting factor F3 (MEROPS identifier M01.021).Aminopeptidase N (APN; CD13; Alanyl aminopeptidase; ), a type II integral membrane protease, consists of a small N-terminal cytoplasmic domain, a single transmembrane domain, and a large extracellular ectodomain that contains the active site. It preferentially cleaves neutral amino acids from the N terminus of oligopeptides and is present in a variety of human tissues and cell types (leukocyte, fibroblast, endothelial and epithelial cells). APN expression is dysregulated in inflammatory diseases such as chronic pain, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, polymyositis/dermatomyosytis and pulmonary sarcoidosis, and is enhanced in tumor cells such as melanoma, renal, prostate, pancreas, colon, gastric and thyroid cancers. It is considered a marker of differentiation since it is predominantly expressed on stem cells and on cells of the granulocytic and monocytic lineages at distinct stages of differentiation. Thus, APN inhibition may lead to the development of anti-cancer and anti-inflammatory drugs [, ].ERAP1 also known as endoplasmic reticulum aminopeptidase associated with antigen processing (ERAAP), adipocyte derived leucine aminopeptidase (A-LAP) or aminopeptidase regulating tumor necrosis factor receptor I (THFRI) shedding (ARTS-1), associates with the closely related ER aminopeptidase ERAP2 (MEROPS identifier M01.024), for the final trimming of peptides within the ER for presentation by MHC class I molecules. ERAP1 is associated with ankylosing spondylitis (AS), an inflammatory arthritis that predominantly affects the spine. ERAP1 also aids in the shedding of membrane-bound cytokine receptors [].The tricorn interacting factor F3, together with factors F1 and F2, degrades the tricorn protease products, producing free amino acids, thus completing the proteasomal degradation pathway. F3 is homologous to F2, but not F1, and shows a strong preference for glutamate in the P1' position [].APQ, also known as laeverin, is specifically expressed in human embryo-derived extravillous trophoblasts (EVTs) that invade the uterus during early placentation []. It cleaves the N-terminal amino acid of various peptides such as angiotensin III, endokinin C, and kisspeptin-10, all expressed in the placenta in large quantities.APN is a receptor for coronaviruses, although the virus receptor interaction site seems to be distinct from the enzymatic site and aminopeptidase activity is not necessary for viral infection []. Insect APNs (MEROPS identifiers M01.013 and M01.030) are also putative Cry toxin receptors. Cry1 proteins are pore-forming toxins that bind to the midgut epithelial cell membrane of susceptible insect larvae, causing extensive damage. Several different toxins, including Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba, Cry1Ca and Cry1Fa, have been shown to bind to APNs; however, a direct role of APN in cytotoxicity has been yet to be firmly established [].