The human alpha 2(XI) collagen gene (COL11A2): completion of coding information, identification of the promoter sequence, and precise localization within the major histocompatibility complex reveal overlap with the KE5 gene.

Type XI collagen, a fibril-forming collagen, is important for the integrity and development of the skeleton because mutations in the genes encoding its consituent alpha chains have been found in some osteochondrodysplasias. We provide data that complete information for the coding sequence of human alpha 2(XI) procollagen, with details of the promoter region and intron-exon organization at the 5' and 3' ends of the gene (COL11A2), including the transcription start and polyadenylation sites. COL11A2 is 30.5 kb with a minimum of 62 exons, differing from other reported fibrillar collagen genes because the amino propeptide is encoded by 14 not 5 to 8 exons. But exon numbers for the carboxy propeptide and 3'-untranslated region are conserved. The promoter region of COL11A2 lacks a TATA box but is GC-rich with two potential SP1 binding sites. Mouse alpha 2(XI) collagen mRNAs undergo complex alternative splicing involving three amino-terminal propeptide exons but only one of these has been reported for COL11A2. We have located these missing human exons and have identified splice signals that point to additional splice variants. We have precisely mapped COL11A2 within the major histocompatibility complex on chromosome 6. The retinoid X receptor beta (RXR beta) gene is located 1.1 kb upstream of COL11A2. KE5, previously thought to be a distinct transcribed gene sequence, was mapped within COL11A2 in the alternatively spliced region, raising the question whether KE5 and COL11A2 are separate genes.