The human COL11A2 gene was analyzed from two overlapping cosmid clones that were previously isolated in the course of searching the human major histocompatibility region (Janatipour, M., Naumov, Y., Ando, A., Sugimura, K., Okamoto, N., Tsuji, K., Abe, K., and Inoko, H. (1992) Immunogenetics 35, 272-278). Nucleotide sequencing defined over 28,000 base pairs of the gene. It was shown to contain 66 exons. As with most genes for fibrillar collagens, the first intron was among the largest, and the introns at the 5-end of the gene were in general larger than the introns at the 3-end. Analysis of the exons coding for the major triple helical domain indicated that the gene structure had not evolved with the genes for the major fibrillar collagens in that there were marked differences in the number of exons, the exon sizes, and codon usage. The gene was located close to the gene for the retinoic X receptor  in a head-to-tail arrangement similar to that previously seen with the two mouse genes (P. Vandenberg and D. J. Prockop, submitted for publication). Also, there was marked interspecies homology in the intergenic sequences. The amino acid sequences and the pattern of charged amino acids in the major triple helix of the ␣2(XI) chain suggested that the chain can be incorporated into the same molecule as ␣1(XI) and ␣1(V) chains but not into the same molecule as the ␣3(XI)/␣1(II) chain. The structure of the carboxyl-terminal propeptide was similar to the carboxyl-terminal propeptides of the pro␣1(XI) chain and pro␣ chains of other fibrillar collagens, but it was shorter because of internal deletions of about 30 amino acids.Over 19 types of collagens are known, each with an apparently unique biological function (1-3). A major subclass is the fibrillar collagens that form ordered extracellular fibrils and that include type I, type II, type III, type V, and type XI collagens. Type I and type III collagens are found in most non-cartilaginous tissues. Type II is found primarily in cartilage where it is the most abundant protein, but it is also present in the vitreous humor and several other tissues in early embryonic development. Type XI collagen was originally recognized as a minor fibrillar collagen in cartilage that was similar to type II collagen. The protein was considered to consist of three ␣ chains referred to as ␣1(XI), ␣2(XI), and ␣3(XI) (4 -6). The ␣3(XI) chain was subsequently shown to be derived from the same gene as the ␣1(II) chain of type II collagen that, by an unknown mechanism, was assembled with the ␣1(XI) and ␣2(XI) chain to form a unique procollagen molecule (4 -9). In further analyses, type XI collagen was found to be closely related in structure to type V collagen, and both type V and type XI collagens were found in small amounts in a variety of cartilaginous and non-cartilaginous connective tissues (10, 11). Amino acid sequencing of fragments of collagen fibrils from mammalian vitreous humor demonstrated that fibrils were assembled from molecules containing ␣1(XI) and ␣2(V) chains (12). Also, during th...