Primary structure of human lumican (keratan sulfate proteoglycan) and localization of the gene (LUM) to chromosome 12q21.3-q22.
A human corneal fibroblast cDNA library was screened with a bovine lumican cDNA probe to obtain three clones. Sequencing of the longest clone (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 resulted in a 9-amino-acid match with the derived primary structure, confirming the identity of these clones. Human lumican displays all of the features of small interstitial proteoglycans: N- and C-terminal domains with highly conserved cysteines and a central domain containing nine repeats of slight variations of the leucine motif LXXLXLXXNXL. Like bovine lumican, the human core protein contains four possible N-glycosylation sites in the central domains, all or some of which are substituted with keratan sulfate side chains. At the amino acid level, it is 90% identical with bovine and 72% identical with the chicken core protein. The gene (LUM) was localized to human chromosome 12 by hybridizing a cDNA probe to a Southern blot containing a human/hamster monochromosomal mapping panel DNA. Further sublocalization to 12q21.3-q22 was performed by the fluorescence in situ hybridization technique using a lumican P1 genomic clone. By immunohistochemical staining, we show lumican'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.
Chakravarti
S
S
Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pennsylvania 15213, USA.
Stallings
R L
RL
SundarRaj
N
N
Cornuet
P K
PK
Hassell
J R
JR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002645:Chickens; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D003315:Cornea / Q000378:metabolism; D006224:Cricetinae; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007632:Keratan Sulfate / Q000235:genetics* / Q000378:metabolism; D000071234:Lumican; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000378:metabolism; D013045:Species Specificity
D011508:Chondroitin Sulfate Proteoglycans; D017931:DNA Primers; D018076:DNA, Complementary; C000604306:LUM protein, human; D000071234:Lumican; D007632:Keratan Sulfate