PRIMARY STRUCTURE OF HUMAN LUMICAN (KERATAN SULFATE PROTEOGLYCAN) ANDLOCALIZATION OF THE GENE (LUM) TO CHROMOSOME 12Q21.3-Q22

A human corneal fibroblast cDNA library was screened with a bovine lum ican cDNA probe to obtain three clones. Sequencing of the longest clon e (1.75 kb) yielded an open reading frame of 1014 bp coding for a 338- amino-acid core protein. Amino acid sequencing of a tryptic peptide re sulted in a g-amino-acid match with the derived primary structure, con firming the identity of these clones. Human lumican displays all of th e features of small interstitial proteoglycans: Nand C-terminal domain s with highly conserved cysteines and a central domain containing nine repeats of slight variations of the leucine motif LXXLXLXXNXL. Like b ovine lumican, the human core protein contains four possible N-glycosy lation sites in the central domains, all or some of which are substitu ted with keratan sulfate side chains. At the amino acid level, it is 9 0% identical with bovine and 72% identical with the chicken core prote in. The gene (LUM) was localized to human chromosome 12 by hybridizing a cDNA probe to a Southern blot containing a human/hamster monochromo somal mapping panel DNA. Further sublocalization to 12q21.3-q22 was pe rformed by the fluorescence in situ hybridization technique using a lu mican P1 genomic clone. By immunohistochemical staining, we show lumic an's presence, not only in the corneal stroma as shown previously, but also in the dermal area of the skin, indicating a wider distribution of this proteoglycan. (C) 1995 Academic Press, Inc.