LGMN
LGMN (legumain) is a lysosomal cysteine protease with strict specificity for hydrolysing asparaginyl bonds. Also known as LGMN1 and PRSC1, it contributes to antigen processing for MHC presentation and to the degradation of internalised EGFR. Browse Assay Genie's current range of LGMN research reagents below, or read on for the biology behind the target.
LGMN is a cysteine endopeptidase with a strict specificity for hydrolysis of asparaginyl bonds. It can also cleave aspartyl bonds slowly, especially under acidic conditions. In the lysosomal and endosomal system it is involved in processing proteins for MHC class II antigen presentation, and NCBI Gene notes a possible role in handling bacterial peptides as well as endogenous proteins. In cross-presenting dendritic cells it also supports MHC class I presentation by cleaving and maturing Perforin-2 (MPEG1), which promotes antigen translocation into the cytosol.
Beyond immunity, the LGMN protein is required for normal lysosomal protein degradation in renal proximal tubules and for normal degradation of internalised EGFR. Through its role in EGFR degradation, it takes part in the regulation of cell proliferation. Enzyme activation is triggered by acidic pH and appears to be autocatalytic. Expression occurs after monocytes differentiate into dendritic cells, and a fully mature, active enzyme is produced after lipopolysaccharide exposure in mature dendritic cells.
The LGMN gene belongs to the HGNC group of cysteine endopeptidases, and the protein belongs to the peptidase C13 family. It was previously named protease, cysteine, 1 (legumain), hence the PRSC1 symbol. The gene has a pseudogene on chromosome 13. Several alternatively spliced transcript variants have been described, but only two have a determined biological validity, and these encode the same isoform. Overexpression of LGMN may be associated with the majority of solid tumour types, which makes it of interest in cancer biology. Mouse and rat both have an orthologous Lgmn gene.
LGMN processes proteins for MHC class II presentation and matures Perforin-2 for MHC class I cross-presentation in dendritic cells.
The enzyme is required for normal lysosomal protein degradation in renal proximal tubules, linking it to lysosomal and kidney biology.
LGMN is needed for normal degradation of internalised EGFR, and so helps regulate cell proliferation.
Overexpression of LGMN may be associated with the majority of solid tumour types, prompting study of its role in cancer.
LGMN is a lysosomal cysteine protease that strictly hydrolyses asparaginyl bonds. It processes proteins for MHC class II antigen presentation, supports MHC class I cross-presentation by maturing Perforin-2, and is required for normal degradation of internalised EGFR.
LGMN is also known as legumain, LGMN1 and PRSC1. Its earlier HGNC name was protease, cysteine, 1 (legumain). Several transcript variants have been described, but only two have determined biological validity, and both encode the same isoform.
Activation is triggered by acidic pH and appears to be autocatalytic. NCBI Gene reports that overexpression of LGMN may be associated with the majority of solid tumour types. Mouse and rat Lgmn orthologues exist; check the datasheet of any product for its validated reactivity.
Substrates and pathway partners of legumain in antigen presentation and EGFR degradation.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q99538; product specifications from Assay Genie datasheets.