High impact information on LRAP

• We show here that one of these, ERAP1, was unable to remove several N-terminal amino acids that were trimmed efficiently by the second enzyme, ERAP2 [1].
• Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum [1].
• A peptide-trimming assay in microsomes revealed additional enzymatic activities, presumably contributed by other unidentified aminopeptidases sharing substrate specificity with ERAP2 [2].
• Human leukocyte-derived arginine aminopeptidase. The third member of the oxytocinase subfamily of aminopeptidases [3].
• In addition to natural hormones such as angiotensin III and kallidin, L-RAP cleaved various N-terminal extended precursors to major histocompatibility complex class I-presented antigenic peptides [3].

Biological context of LRAP

• Like other proteins involved in antigen presentation, L-RAP is induced by interferon-gamma [3].
• Among various synthetic substrates tested, L-RAP revealed a preference for arginine, establishing that the enzyme is a novel arginine aminopeptidase with restricted substrate specificity [3].
• However, this dramatic genetic effect on LRAP expression justifies further investigation of association with other phenotypes, especially autoimmune and related to host defense to specific pathogens [4].
• This study was designed to confirm that LRAP expression in B-cell derived lines is controlled by a haplotype marked by rs2762 and to see whether this would be the basis of an association with type 1 diabetes (T1D) [4].
• Thus, low and/or imbalanced expression of ERAP1 and probably ERAP2 may cause improper Ag processing and favor tumor escape from the immune surveillance [2].

Anatomical context of LRAP

• Immunocytochemical analysis indicates that L-RAP is located in the lumenal side of the endoplasmic reticulum [3].
• ERAP1 and ERAP2 expression was detectable in all of the EBV-B and tumor cell lines, but in the latter it was extremely variable, sometimes barely detectable, and not coordinated [2].
• In humans, at least two ER resident aminopeptidases, ERAP1 and ERAP2, contribute to trimming of human leukocyte antigen class I ligands [5].

Other interactions of LRAP

• Proliferation of papilla cells was enhanced by recombinant human amelogenin rH72 (LRAP+ exon 4), while pulp cells responded to both rH72 and rH58 (LRAP), with no effect by rH174 [6].

References