a negatively-charged N-terminal domain containing sulfated tyrosine and disulfide bond(s);
ten tandem leucine-rich repeats allowing lumican to bind to other extracellular components such as collagen;
a carboxyl terminal domain of 50 amino acid residues containing two conserved cysteines 32 residues apart.
There are four N-linked sites within the leucine-rich repeat domain of the
protein core that can be substituted with
keratan sulfate. The core protein of lumican (like
decorin and
fibromodulin) is horseshoe shaped. This enables it bind to
collagen molecules within a collagen fibril, thus helping keep adjacent fibrils apart.[10]
Function
Lumican is a major
keratan sulfateproteoglycan of the cornea but is ubiquitously distributed in most mesenchymal tissues throughout the body.[11] Lumican is involved in collagen fibril organization and circumferential growth,
corneal transparency, and epithelial cell migration and tissue repair.[6] Corneal transparency is possible due to the exact alignment of
collagen fibers by lumican (and
keratocan) in the intrafibrillar space.
Clinical significance
Mice that have the lumican gene knocked out (Lum-/-) develop opacities of the
cornea in both eyes and fragile
skin.[12] The lumican (LUM) gene was thought to be a candidate susceptibility gene for high
myopia; however, a meta-analysis showed no association between LUM polymorphism and high myopia susceptibility in all genetic models studied.[13]
Lum knockout mice also have abnormal
collagen in their
heart tissue, with fewer and thicker fibrils.[14] Mice deficient in both lumican and
fibromodulin develop severe
tendinopathy (
tendonpathology), revealing the importance of these SLRPs in the development of correctly sized and aligned
collagen fibers in
tendon.[15] Along with other
extracellular matrix components, lumican expression was increased in equine
flexortendons six weeks after an injury.[16]
Lumican is present in the
extracellular matrix of uteral tissues in fertile women.[17] There is an increase of lumican during the proliferative to secretory phase of the
endometrium. In menopausal endometrial tissue, the level of lumican expression decreases and is also low in pathological compared to normal
endometrium.
Lumican is highly expressed in pleural effusions (
lung fluid) of patients with
adenocarcinoma.[18] Its expression was low in
cancer cells but high in the
extracellular matrix surrounding the
tumor. Lumican expression was not associated with tumor grade or stage. In about half the patients with pancreatic ductal
adenocarcinoma tested,[19] lumican in the
extracellular matrix around the
tumor was associated with a reduction in metastatic recurrence after surgery and with a three-fold longer survival than patients without stromal lumican. As lumican can directly bind to and inhibit
matrix metalloproteinase-14 (
MMP14), lumican may limit tumor progression by preventing
extracellular matrixcollagenproteolysis by this
enzyme.[20]
^Chakravarti S, Stallings RL, SundarRaj N, Cornuet PK, Hassell JR (Jun 1995). "Primary structure of human lumican (keratan sulfate proteoglycan) and localization of the gene (LUM) to chromosome 12q21.3-q22". Genomics. 27 (3): 481–8.
doi:
10.1006/geno.1995.1080.
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^Scott JE (1996). "Proteodermatan and proteokeratan sulfate (decorin, lumican/fibromodulin) proteins are horseshoe shaped. Implications for their interactions with collagen". Biochemistry. 35 (27): 8795–9.
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10.1021/bi960773t.
PMID8688414.
^Li M, Zhai L, Zeng S, Peng Q, Wang J, Deng Y, Xie L, He Y, Li T (Jul 2014). "Lack of association between LUM rs3759223 polymorphism and high myopia". Optometry and Vision Science. 91 (7): 707–12.
doi:
10.1097/OPX.0000000000000302.
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^Mienaltowski MJ, Birk DE (2014). "Mouse models in tendon and ligament research". Progress in Heritable Soft Connective Tissue Diseases. Advances in Experimental Medicine and Biology. Vol. 802. pp. 201–30.
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^Lucariello A, Trabucco E, Boccia O, Perna A, Sellitto C, Castaldi MA, De Falco M, De Luca A, Cobellis L (2015). "Small leucine rich proteoglycans are differently distributed in normal and pathological endometrium". In Vivo. 29 (2): 217–22.
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Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4.
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Rada JA, Cornuet PK, Hassell JR (Jun 1993). "Regulation of corneal collagen fibrillogenesis in vitro by corneal proteoglycan (lumican and decorin) core proteins". Experimental Eye Research. 56 (6): 635–48.
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