Disease relevance of LGMN

• CONCLUSIONS: The legumain expression may be involved in colorectal cancer development and have a prognostic value in the patients [1].
• RESULTS: Legumain expression was increased in primary tumors compared with distant or adjacent normal mucosa (P < 0.05), but there was no significant change between primary tumors and metastases (P > 0.05) [1].
• Using the tetanus toxin C fragment protein as a test case, we show that spontaneous deamidation of asparagine residues interferes with processing by the enzyme asparagine endopeptidase (AEP) and contributes to diminished antigen presentation [2].
• Identification of human asparaginyl endopeptidase (legumain) as an inhibitor of osteoclast formation and bone resorption [3].
• C. elegans cystatins lacked a domain involved in inhibition of legumain-like proteases that was present in O. volvulus cystatin [4].

Psychiatry related information on LGMN

• This study used visual and auditory evoked potentials (VEP and AEP) to study low-level sensory processing in a group of 15 unmedicated subjects with obsessive-compulsive disorder (OCD) and 30 age-matched, gender-matched, and handedness-matched normal controls [5].
• It was concluded that later SEP amplitude correlates of psychopathology are little influenced by AP and TR drugs, but that VEP and AEP results are modified [6].
• Sociopaths and controls did not differ in reaction time, vertex and occipital AEP amplitude or latency, and power spectral density of the EEG [7].
• Scalp-recorded sensory evoked potentials (EPs) elicited by left and right median nerve stimulation (LSEP and RSEP), checkerboard pattern flash (VEP) and acoustic click (AEP) were obtained in 22 individuals 'at risk' (AR) for Huntington's disease and 22 hospitalized neurotic patients matched for age, gender and intelligence [8].
• Latencies of the P2 and N2 components of the AEP were noticeably shorter in the Tourette's syndrome patient than in the control group [9].

High impact information on LGMN

• We also show that N-glycosylation of asparagine residues blocks AEP action in vitro [10].
• In vivo, these inhibitors slow TTCF presentation to T cells, whereas preprocessing of TTCF with AEP accelerates its presentation, indicating that this enzyme performs a key step in TTCF processing [10].
• We designed competitive peptide inhibitors of B-cell asparaginyl endopeptidase (AEP) that specifically block its proteolytic activity and inhibit processing of TTCF in vitro [10].
• 11S seed storage proteins are synthesized as precursors that are cleaved post-translationally in storage vacuoles by an asparaginyl endopeptidase [11].
• Both CSF-induced macrophages expressed similar sets of genes except for several genes such as monocyte-derived chemokine (MDC), legumain, prostaglandin D synthetase, and lysosomal sialoglycoprotein [12].

Chemical compound and disease context of LGMN

• OBJECTIVES: The present study examined the effects of a single intranasal administration of CCK-8 on auditory brain potential (AEP) signs of cognitive processing and on motor performance in patients with Parkinson's disease (PD), known to originate from degeneration of DA neurons primarily in the nigrostriatal DA system [13].
• We investigated the effect of isoproterenol and terbutaline sulfate on the development of acute edematous (AEP) and acute hemorrhagic (AHP) pancreatitis in a feline model of biliary pancreatitis [14].
• Silencing of cystatin M in metastatic oral cancer cell line MDA-686Ln by siRNA increases cysteine proteinases and legumain activities, cell proliferation and in vitro invasion [15].

Biological context of LGMN

• Cystatin M/E is a high affinity inhibitor of cathepsin V and cathepsin L by a reactive site that is distinct from the legumain-binding site. A novel clue for the role of cystatin M/E in epidermal cornification [16].
• Legumain is a cysteine endopeptidase that shows strict specificity for hydrolysis of asparaginyl bonds [17].
• This encoded a protein with a predicted Mr of 49 kDa, the amino acid sequence of which showed good homology (34-40% identity) to legumains from Schistosoma mansoni, human and rat and contained a legumain-like active site [18].
• RT-PCR indicated that the legumain transcript was expressed from the L4 life-cycle stage onwards [18].
• Asparaginyl endopeptidase (AEP), also known as legumain, is a cysteine protease that has been ascribed roles in antigen presentation yet its exact role in human biology remains poorly understood [19].

Anatomical context of LGMN

• Moreover, we show that human monocyte-derived dendritic cells harbor inactive proforms of AEP that become activated upon maturation of dendritic cells with lipopolysaccharide [20].
• Whereas CTSL and AEP were broadly expressed in epithelial cells of the skin, we found a specific colocalization of cystatin M/E and CTSV in the stratum granulosum and in the root sheets of the hair follicle, using immunofluorescence microscopy [21].
• In addition, it is demonstrated that the early components of the middle latency AEP (No and Na) largely reside within the time domain between the termination of the BAEP components and the PCAEP which would be consistent with their being far field reflections of midbrain and subcortical auditory activity [22].
• Somatosensory (SEP) to left and right median nerve stimuli, visual (VEP), and auditory (AEP) EPs were recorded from one eye and 14 scalp leads [6].
• In contrast to monocytes, LPS priming provoked an increase of legumain expression in B cells [23].

Associations of LGMN with chemical compounds

• We conclude that legumain and papain-like cysteine proteases are inhibited by two distinct non-overlapping sites [16].
• However they were also effective labels of the clan CD protease legumain and showed unexpected crossreactivity with the clan CA protease cathepsin B. Interestingly, related aza peptides containing an acyloxymethyl ketone reactive group were relatively weak but highly selective labels of caspases [24].
• Mammalian legumain is a cysteine endopeptidase, inhibited by iodoacetamide and maleimides, but unaffected by compound E64 (trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane) [17].
• Pig legumain is a glycoprotein of about 34 kDa, decreasing to 31 kDa on deglycosylation [17].
• We report here, the use of a positional scanning combinatorial library of peptide AOMKs containing a P1 aspartic acid to probe the P2, P3, and P4 subsite specificity of endogenous legumain [19].

Regulatory relationships of LGMN

• More 62 kDa gelatinase A was detected in cultures of C13 cells that over-expressed legumain than in those of the control HEK293 cells [25].
• Legumain also activated progelatinase A when it was in complex with TIMP-2 [25].

Other interactions of LGMN

• Eighteen of these genes have not been associated previously with plaque instability, including the metalloproteinase, ADAMDEC1 (approximately 37-fold), retinoic acid receptor responder-1 (approximately 5-fold), and cysteine protease legumain (approximately 3-fold) [26].
• Identification and characterization of an asparaginyl proteinase (legumain) from the parasitic nematode, Haemonchus contortus [18].
• The structures reveal differences in the peptidase-interacting regions when compared with other cystatins, providing plausible explanations for the restricted inhibitory specificity of cystatin D for some papain-like peptidases and its lack of reactivity toward legumain-related enzymes [27].
• Identification, cDNA cloning and possible roles of seed-specific rice asparaginyl endopeptidase, REP-2 [28].
• The present study shows that REP-2 is an asparaginyl endopeptidase that acts as an activator of REP-1, and we separated it into two forms, REP-2alpha (39 kDa) and REP-2beta (40 kDa), using ion-exchange chromatography and gel filtration chromatography [28].

Analytical, diagnostic and therapeutic context of LGMN

• EXPERIMENTAL DESIGN: We investigated legumain expression in 164 primary colorectal cancers, 34 corresponding distant normal mucosa samples, 89 adjacent normal mucosa samples, and 33 lymph node metastases using immunohistochemistry [1].
• Molecular cloning of a human cDNA encoding putative cysteine protease (PRSC1) and its chromosome assignment to 14q32.1 [29].
• A ternary complex between legumain, cystatin C, and papain was demonstrated by gel filtration supported by immunoblotting [30].
• Asparaginyl endopeptidase of jack bean seeds. Purification, characterization, and high utility in protein sequence analysis [31].
• Sequence alignments and molecular modeling led to the suggestion that a loop located on the opposite side to the papain-binding surface, between the alpha-helix and the first strand of the main beta-pleated sheet of the cystatin structure, could be involved in legumain binding [30].

References