Alternative titles; symbols
HGNC Approved Gene Symbol: LGMN
Cytogenetic location: 14q32.12 Genomic coordinates (GRCh38): 14:92,703,809-92,748,627 (from NCBI)
LGMN, or AEP, is a lysosomal cysteine protease that cleaves after asparagine residues. It contributes to the processing of antigenic peptides and to the processing of cathepsins B (CTSB; 116810), H (CTSH; 116820), and L (CTSL1; 116880) from single-chain forms into active 2-chain forms (Liu et al., 2008).
As part of a random cDNA sequencing project, Tanaka et al. (1996) identified a novel human cysteine protease, which they designated PRSC1, with 40% amino acid identity to hemoglobinase of the schistosome parasite and 36% identity to a vacuolar processing enzyme of the soybean. The predicted protein contains 433 amino acids with a calculated mass of 49 kD. Northern blotting showed expression in most human tissues, with highest levels in kidney, heart, and placenta.
Chen et al. (1997) purified and cloned the PRSC1 gene, which they termed legumain. The observed size of the protein is approximately 34 kD. They showed that the enzyme is glycosylated and acts as a cysteine peptidase with specificity for asparaginyl bonds.
Ischemia and seizure cause excessive neuronal excitation that is associated with brain acidosis and neuronal cell death. Liu et al. (2008) found that the neurotoxin kainic acid activated Aep in mouse brain and triggered degradation of Set (600960), a DNase inhibitor, followed by DNA nicking and neuronal cell death. Pike-L (CENTG1; 605476) strongly bound Set in the nucleus and protected Set from proteolytic cleavage by Aep in vitro and in vivo, thereby diminishing DNA damage and neuronal cell death. Kainic acid or stroke failed to provoke DNA nicking and neuronal cell death in Aep-deficient mice.
Using fluorescence in situ hybridization, Tanaka et al. (1996) mapped the LGMN gene to chromosome 14q32.1.
Chen, J.-M., Dando, P. M., Rawlings, N. D., Brown, M. A., Young, N. E., Stevens, R. A., Hewitt, E., Watts, C., Barrett, A. J. Cloning, isolation, and characterization of mammalian legumain, an asparaginyl endopeptidase. J. Biol. Chem. 272: 8090-8098, 1997. [PubMed: 9065484] [Full Text: https://doi.org/10.1074/jbc.272.12.8090]
Liu, Z., Jang, S.-W., Liu, X., Cheng, D., Peng, J., Yepes, M., Li, X., Matthews, S., Watts, C., Asano, M., Hara-Nishimura, I., Luo, H. R., Ye, K. Neuroprotective actions of PIKE-L by inhibition of SET proteolytic degradation by asparagine endopeptidase. Molec. Cell 29: 665-678, 2008. [PubMed: 18374643] [Full Text: https://doi.org/10.1016/j.molcel.2008.02.017]
Tanaka, T., Inazawa, J., Nakamura, Y. Molecular cloning of a human cDNA encoding putative cysteine protease (PRSC1) and it chromosome assignment to 14q32.1 Cytogenet. Cell. Genet. 74: 120-123, 1996. [PubMed: 8893817] [Full Text: https://doi.org/10.1159/000134397]