Alternative titles; symbolsLOXCHGNC Approved Gene Symbol: LOXL4Cytogenetic location: 10q24.2 Genomic coordinates (GRCh38): 10:98,247,689-98,268,220 (from NCB...
Alternative titles; symbols
HGNC Approved Gene Symbol: LOXL4
Cytogenetic location: 10q24.2 Genomic coordinates (GRCh38): 10:98,247,689-98,268,220 (from NCBI)
LOXL4 is a member of the lysyl oxidase (LOX; 153455) family of amine oxidases that catalyze the final enzymatic step required for the lysine-derived crosslinks essential for the formation of collagen fibrils and insoluble elastic fibers within the extracellular matrix. These enzymes may also contribute to developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis (summary by Asuncion et al., 2001).
▼ Cloning and Expression
Using the conserved copper-binding domain of LOXL2 (606663) as the query in a database search, followed by PCR of placenta RNA, Asuncion et al. (2001) cloned LOXL4. The deduced 756-amino acid protein contains an N-terminal signal sequence, 4 scavenger receptor cysteine-rich (SRCR) domains, lysyl and tyrosyl residues that form the carbonyl cofactor within the catalytic site, and a cytokine receptor (see 300357)-like domain at the C terminus. LOXL4 shares 51% and 54% amino acid identity with LOXL2 and LOXL3 (607163), respectively. The second SRCR domain of LOXL4 is the most divergent, containing an additional 13 amino acids encoded by a short exon not found within LOXL2 or LOXL3. Northern blot analysis revealed near ubiquitous expression of a 3.5-kb transcript. Highest levels were detected in pancreas and testis, with intermediate levels in placenta, lung, liver, skeletal muscle, spleen, prostate, ovary, and small intestine, low levels in heart, brain, thymus, and colon, and no expression in leukocytes. LOXL4 mRNA was expressed in fibroblasts, smooth muscle cells, and osteosarcoma cells, but not in cancer cell lines originating from colon, prostate, and breast carcinoma.
Maki et al. (2001) identified LOXL4 by database searching and cloned the full-length cDNA by PCR of kidney and fetal cDNA libraries. They identified 10 cysteine residues highly conserved in all human LOX isoforms, and several O- and N-linked glycosylation sites. Northern blot analysis confirmed the results of Asuncion et al. (2001), with highest levels of an approximately 4-kb transcript detected in skeletal muscle, testis, and pancreas, with no expression detected in blood leukocytes. Western blot analysis of LOXL4 expressed by transfected fibrosarcoma cells revealed secretion of a glycosylated protein with an apparent mass greater than the predicted 84.5 kD.
Ito et al. (2001) cloned mouse Loxl4, which they designated Loxc, by subtractive hybridization between differentiated and calcified mouse chondrocytes. The predicted protein contains 757 amino acids. Northern blot analysis detected a 5.4-kb transcript in osteoblastic cells and in an embryonic fibroblast line, but not in NIH 3T3 fibroblasts and mouse myoblastic cells. Western blot analysis revealed a protein with an apparent molecular mass of 82 kD.
▼ Gene Function
Ito et al. (2001) found that the levels of mouse Loxl4 increased in a chondrogenic mouse cell line following differentiation. Immunolocalization of Loxl4 in adult mouse sections showed expression localized to hypertrophic and calcified chondrocytes of growth plates. Mouse Loxl4 expressed by transfected COS-7 cells was secreted to the medium and showed LOX activity in both type I and type II chick embryo collagens, and the activity was inhibited by a specific inhibitor of LOX.
▼ Gene Structure
Asuncion et al. (2001) determined that the LOXL4 gene contains 14 exons.
By genomic sequence analysis, Asuncion et al. (2001) mapped the LOXL4 gene to chromosome 10q24.