The Human Lumican Gene

Abstract

A human lumican cDNA sequence was derived by polymerase chain reaction techniques from RNA obtained from intestine, placenta, and articular cartilage. A contiguous sequence of 1729 bases was obtained corresponding to an observed message size of 1.8 kilobases (kb). The cDNA sequence consists of an 80-base pair (bp) 5-untranslated region, a 1014-bp coding sequence, and a 618-bp 3-untranslated region terminating in a 17-bp poly(A) tail. The deduced lumican protein sequence has 338 amino acids, including a putative 18-residue signal peptide. The human lumican gene was shown to be spread over about 7.5 kb of genomic DNA and to be located on chromosome 12q22. The gene consists of 3 exons separated by introns of 2.2 and 3.5 kb. The shorter 5-intron resides 21 bases prior to the translation initiation codon, and the 3-intron resides 152 bases prior to the translation termination codon. The lumican message is expressed at high levels in adult articular chondrocytes but at low levels in the young juvenile. This age-related trend in message level is not, however, common to all tissues in which the lumican gene is expressed. Lumican is present in the extracellular matrix of human articular cartilage at all ages, although its abundance is far greater in the adult. In the adult cartilage lumican exists predominantly in a glycoprotein form lacking keratan sulfate, whereas the juvenile form of the molecule is a proteoglycan.Lumican belongs to the family of relatively small leucine-rich proteoglycans that are present in the extracellular matrix of many tissues. In addition to lumican, the family includes decorin, biglycan, and fibromodulin (1, 2), and each family member has a common structure consisting of a central region of leucine-rich repeats that are flanked at either side by a disulfide-bonded domain. The central leucine-rich region possesses attachment sites for N-linked oligosaccharides, which in fibromodulin and lumican may be modified by sulfation of their polylactosamine units to yield keratan sulfate. Fibromodulin and lumican may therefore also be classed as keratan sulfateproteoglycans (KS-PG).

Expression and Localization of Lumican in the Ischemic and Reperfused Rat Heart.

“…3,8,13,20 In the adult cornea, lumican exists as PG; however, in the embryonic cornea, lumican is reported to be localized as a glycoprotein. The change from glycoprotein to PG may have an important role in corneal transparency.…”

“…21 In the human juvenile cartilage, all lumican exists as a keratan sulfate PG; however, in the adult most of the lumican exists as a glycoprotein form that is devoid of polylactosamine chains. 3,22 The core protein of lumican is reported to affect collagen fibrillogenesis. 23 However, little is known about the role of the glycosyl side chains of lumican protein.…”

MATRIX PROTEOGLYCANS: From Molecular Design to Cellular Function

“…In contrast to Class I, members of Class II SLRPs are encoded by three exons, with all ten LRRs encoded by a single large exon (222,223). In these genes, the introns are positioned at identical sites, just proximal to the translation initiation and termination codons, respectively (223).…”

Knockdown of Zebrafish Lumican Gene (zlum) Causes Scleral Thinning and Increased Size of Scleral Coats

“…In corneal stroma, lumican is a KSPG, whereas lumican presents as an under-or unglycanated glycoprotein in other tissues (9,13,14,21). It has been proposed that the horseshoe-shaped lumican core protein binds collagen molecules to modulate collagen fibril diameter, whereas the N-linked glycosaminoglycan chains regulate fibril spacing and stromal hydration for the formation and maintenance of transparent corneas (22)(23)(24).…”

“…biglycan (Xq27ter), decorin (12q21-22), lumican (12q21. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22], and DSPG3 (12q21) (4 -9). Our previous study showed that certain variations (rs3759223 (C3 T)) of single nucleotide polymorphism in the lumican regulatory region may influence the promoter activities of lumican and affect fibrillogenesis in myopic eyes (10).…”