Genomic Organization and Characterization of the Human Type XXI Collagen ( COL21A1 ) Gene

We cloned a 4.1-kb full-length cDNA based on a reported human genomic clone containing a partial open reading frame (ORF) coding for a novel collagen-like protein. Sequence analysis indicated that the ORF codes for the α1-chain of type XXI collagen. Assembly of the genomic data reveals a complete sequence of the human gene COL21A1. COL21A1 is localized to chromosome 6p11.2–12.3, spanning 337 kb in size. The gene contains 31 exons, in which the 5′-untranslated exons 1 and 1a are alternatively spliced. The exon/domain organization of COL21A1 resembles that of the reported FACIT collagen genes, including COL9A1, COL9A2, COL9A3, and COL19A1, suggesting that these genes may have derived from the same ancestor FACIT gene by duplication. The expression of COL21A1 in human tissues is developmentally regulated, with a higher level at fetal stages. Type XXI collagen is an extracellular matrix component of the blood vessel walls, secreted by smooth-muscle cells. Platelet-derived growth factor (PDGF) has a pronounced effect on the stimulation of COL21A1 expression in cultured aortic smooth-muscle cells, suggesting that α1(XXI) collagen may contribute to the extracellular matrix assembly of the vascular network during blood vessel formation.