Mimecan, the 25-kDa corneal keratan sulfate proteoglycan, is a product of the gene producing osteoglycin.
Bovine cornea contains three unique keratan sulfate proteoglycans (KSPGs), of which two (lumican and keratocan) have been characterized using molecular cloning. The gene for the third protein (KSPG25) has not been identified. This study examined the relationship between the KSPG25 protein and the gene for osteoglycin, a 12-kDa bone glycoprotein. The N-terminal amino acid sequence of KSPG25 occurs in osteoglycin cDNA cloned from bovine cornea. The osteoglycin amino acid sequence makes up the C-terminal 47% of the deduced sequence of the KSPG25 protein. Antibodies to osteoglycin reacted with intact corneal KSPG, with KSPG25 protein, and with a 36-kDa protein, distinct from lumican and keratocan. KSPG25-related proteins, not modified with keratan sulfate, were also detected in several connective tissues. Northern blot analysis showed mRNA transcripts of 2.4, 2.5, and 2.6 kilobases in numerous tissues with the 2.4-kilobase transcript enriched in ocular tissues. Ribonuclease protection analysis detected several protected KSPG25 mRNA fragments, suggesting alternate splicing of KSPG25 transcripts. We conclude that the full-length translation product of the gene producing osteoglycin is a corneal keratan sulfate proteoglycan, also present in many non-corneal tissues without keratan sulfate chains. The multiple size protein products of this gene appear to result from in situ proteolytic processing and/or alternative splicing of mRNA. The name mimecan is proposed for this gene and its products.
Funderburgh
J L
JL
Division of Biology, Kansas State University, Manhattan, Kansas 66506-4901, USA.
Corpuz
L M
LM
Roth
M R
MR
Funderburgh
M L
ML
Tasheva
E S
ES
Conrad
G W
GW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics*; D003001:Cloning, Molecular; D003315:Cornea / Q000378:metabolism*; D018076:DNA, Complementary; D006023:Glycoproteins / Q000235:genetics*; D007632:Keratan Sulfate / Q000235:genetics*; D000071234:Lumican; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics
D011508:Chondroitin Sulfate Proteoglycans; D018076:DNA, Complementary; D006023:Glycoproteins; D000071234:Lumican; D012333:RNA, Messenger; D007632:Keratan Sulfate