Central nervous system, uterus, heart, and leukocyte expression of the LOXL3 gene, encoding a novel lysyl oxidase-like protein.
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.
Jourdan-Le Saux
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Pacific Biomedical Research Center, University of Hawaii, 1993 East-West Road, Honolulu, Hawaii, 96822
Tomsche
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Ujfalusi
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Jia
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Csiszar
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D017398:Alternative Splicing; D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D002490:Central Nervous System / Q000378:metabolism*; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000378:metabolism; D016208:Databases, Factual; D005091:Exons; D020224:Expressed Sequence Tags; D005260:Female; D006801:Humans; D007438:Introns; D007962:Leukocytes / Q000378:metabolism*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D008249:Protein-Lysine 6-Oxidase / Q000096:biosynthesis* / Q000235:genetics*; D014018:Tissue Distribution; D014599:Uterus / Q000378:metabolism*
D018076:DNA, Complementary; D000594:Amino Acid Oxidoreductases; C435668:LOXL3 protein, human; D008249:Protein-Lysine 6-Oxidase