The complete derived amino acid sequence of human lysyl oxidase and assignment of the gene to chromosome 5 (extensive sequence homology with the murine ras recision gene).
Lysyl oxidase catalyzes the oxidation of lysine residues to alpha-aminoadipic-delta-semialdehyde. This is the first step in the covalent cross-linking of collagen and tropoelastin and results in the formation of insoluble collagen and elastic fibers in the extracellular matrix. We have characterized the complete nucleotide sequence of human lysyl oxidase (EC 1.4.3.13) and compared the derived amino acid sequence (417-amino acids) to rat lysyl oxidase and the mouse ras recision gene (rrg). 88% of amino acids and 83% of nucleotides were conserved between human and rat lysyl oxidase. The mouse ras recision gene demonstrated 89% conservation of amino acids with human lysyl oxidase. The sequence conservation was not evenly distributed along the molecule. The carboxy terminus of the protein, which contains the putative copper binding sites and is likely to be the catalytically active domain, was more highly conserved than the amino terminus. The 89% amino acid sequence similarity between the murine ras recision gene and human lysyl oxidase suggests that they are the same gene product. Therefore, in addition to cross linking of extracellular matrix proteins, lysyl oxidase may have a direct role in tumor suppression. Northern blot analysis of poly A+RNA from cultured skin fibroblasts revealed at least three-distinct transcripts, sized 4.8 kb, 3.8 kb and 2.0 kb. In addition, using a panel of human mouse cell hybrids, the lysyl oxidase gene was assigned to human chromosome 5.
Dept. of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903.
T J
TJ
Mariani
P C
PC
Trackman
H M
HM
Kagan
R L
RL
Eddy
T B
TB
Shows
C D
CD
Boyd
S B
SB
Deak
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D015179:Colorectal Neoplasms / Q000235:genetics; D004247:DNA / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005796:Genes; D011905:Genes, ras; D020022:Genetic Predisposition to Disease; D006801:Humans; D006822:Hybrid Cells; D051379:Mice / Q000235:genetics; D008969:Molecular Sequence Data; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics* / Q000502:physiology; D051381:Rats / Q000235:genetics; D017385:Sequence Homology; D013045:Species Specificity
D016326:Extracellular Matrix Proteins; C077112:Lox protein, mouse; D004247:DNA; D008249:Protein-Lysine 6-Oxidase