A tissue-specific variant of the human lysyl oxidase-like protein 3 (LOXL3) functions as an amine oxidase with substrate specificity.
The human lysyl oxidase-like 3 (LOXL3) encodes a member of the emerging family of lysyl oxidase (LOX) that functions as a copper-dependent amine oxidase. The LOXL3 protein contains four scavenger receptor cysteine-rich domains in the N terminus in addition to the C-terminal characteristic domains of the LOX family, such as a copper binding domain, a cytokine receptor-like domain and residues for the lysyl-tyrosyl quinone cofactor. Using BLASTN searches, we identified a LOXL3 variant LOXL3-sv1 that lacked the sequences corresponding to exons 1, 2, 3, and 5 of LOXL3. LOXL3-sv1 showed an exon-intron structure distinct from LOXL3, additionally containing an 80-bp sequence corresponding to intron 3 of LOXL3 in the 5'-UTR and a 561-bp sequence corresponding to the 3'-flanking genomic region of exon 14 in the 3'-UTR. LOXL3-sv1 was predicted to encode a polypeptide of 392 amino acids that contains the C-terminal domains required for amine oxidase activity but lacks the N-terminal SRCR domains 1, 2, and 3. The recombinant LOXL3-sv1 protein showed a beta-aminopropionitrile-inhibitable amine oxidase activity toward elastin and collagen with substrate specificity. In RT-PCR assays with various human tissues, LOXL3-sv1 and LOXL3 showed distinct expression patterns. Further, luciferase reporter assays revealed a strong promoter element in intron 3 that probably functions as a regulatory region for the expression of LOXL3-sv1. These findings strongly indicate that LOXL3 encodes two variants, LOXL3 and LOXL3-sv1, both of which function as amine oxidases with distinct tissue and substrate specificities from one another.
Lee
Jae-Eun
JE
Department of Biological Science, Sookmyung Women's University, Chungpa-Dong, Yongsan-Gu, Seoul, 140-742, South Korea.
Kim
Youngho
Y
D000594:Amino Acid Oxidoreductases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D005260:Female; D014644:Genetic Variation; D006801:Humans; D066298:In Vitro Techniques; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism
D018076:DNA, Complementary; D012333:RNA, Messenger; D014157:Transcription Factors; D000594:Amino Acid Oxidoreductases; C435668:LOXL3 protein, human