Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.3.13 (lysyl oxidase)
 1,248 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A BLASTN search using the mouse lor-2 cDNA identified three overlapping ESTs (AI752772, AA852888, and R55706) in the GenBank database. These expressed sequence tags were assembled into a contig of 3121 nucleotides with an open reading frame of 2262 bp. The encoded putative polypeptide of 754 amino acids presented all structural characteristics of the lysyl oxidase (LOX) enzyme family, a copper-binding site with four histidyl residues, the lysyl and tyrosyl residues known to be involved in LOX enzyme in the formation of the quinone cofactor and surrounding sequences, and the cytokine receptor-like domain. In addition, four scavenger receptor cysteine-rich (SRCR) domains were found in the N-terminal region of the protein. The gene encoding this new cDNA, which we have referred to as human lysyl oxidase-like 3 (humanLOXL3), has been mapped to chromosome 2p13.3, overlapping at its 3' end the HtrA2 serine protease gene. The structure of the humanLOXL3 gene was deduced from the BAC clone bac91a19 sequence and contained 14 exons. The expression pattern of this new member of the LOX gene family appears to be different from that of the LOX and LOX-like genes, as the central nervous system, neurons, and also leukocytes expressed humanLOXL3. A BLASTN search of the human EST database indicated the presence of ESTs, corresponding to alternative splice variants of LOXL3, that lacked exon 5 and exon 8. The putative resulting protein retained the region encoding the structural and functional elements of the amine oxidase but the second and fourth SRCR domains were truncated and the potential BMP-1 cleavage site was not present. The presence of domains unrelated to the traditional amine oxidase activity is a strong indication that humanLOXL3 might fulfill other functions in addition to intrinsic enzyme activity.
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PMID:Central nervous system, uterus, heart, and leukocyte expression of the LOXL3 gene, encoding a novel lysyl oxidase-like protein. 1138 57

Fibroblast activation protein-alpha (FAP) is a cell-surface transmembrane-anchored dimeric protease. This unique, constitutively active serine protease has both dipeptidyl aminopeptidase and endopeptidase activities and can hydrolyze the post-proline bond. FAP expression is very low in adult organs but is upregulated by activated fibroblasts in sites of tissue remodeling, including fibrosis, atherosclerosis, arthritis and tumors. To identify the endogenous substrates of FAP, we immortalized primary mouse embryonic fibroblasts (MEFs) from FAP gene knockout embryos and then stably transduced them to express either enzymatically active or inactive FAP. The MEF secretomes were then analyzed using degradomic and proteomic techniques. Terminal amine isotopic labeling of substrates (TAILS)-based degradomics identified cleavage sites in collagens, many other extracellular matrix (ECM) and associated proteins, and lysyl oxidase-like-1, CXCL-5, CSF-1, and C1qT6, that were confirmed in vitro In addition, differential metabolic labeling coupled with quantitative proteomic analysis also implicated FAP in ECM-cell interactions, as well as with coagulation, metabolism and wound healing associated proteins. Plasma from FAP-deficient mice exhibited slower than wild-type clotting times. This study provides a significant expansion of the substrate repertoire of FAP and provides insight into the physiological and potential pathological roles of this enigmatic protease.
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PMID:Identification of Novel Natural Substrates of Fibroblast Activation Protein-alpha by Differential Degradomics and Proteomics. 3025 79