The human type II procollagen gene: identification of an additional protein-coding domain and location of potential regulatory sequences in the promoter and first intron.

The complete DNA sequence (6 kb) of the 5' portion of the human type II procollagen gene (COL2A1) was determined from the promoter through the third exon including intron sequences and 690 bp of 5' flanking sequence. Three regions between -501 and -649 in the human promoter share high sequence homology to the rat type II procollagen gene and suggest that the functional sequences within the promoter may extend to at least 649 bp upstream from the start site of transcription. The first intron of the human gene contains elements known to play a role in transcription of other genes: three GC boxes, an inverted repeat with homology to a serum responsive element, a viral core enhancer motif, a high-affinity recognition sequence for nuclear factor-1, and an alternating purine/pyrimidine stretch composed of GT repeats. Both the promoter and a portion of the first intron have a high percentage of G + C residues and a high frequency of CpG dinucleotides. In addition, a protein domain that has been identified in the human COL2A1 gene is present in pro-alpha 1(I) and pro-alpha 1(III) collagen but was not previously described for pro-alpha 1(II) collagen. On the basis of this new information we present a modified gene structure for the exons encoding the pro-alpha 1(II) collagen NH2-propeptide.