Genomic Characterization of Human DSPG3

Overview

Journal Genome Res

Specialty Genetics

Date 1999 May 18

PMID 10330124

Citations 4

Authors

M Deere

J L Dieguez

S J Yoon

A de la Chapelle

J T Hecht

Affiliations

Soon will be listed here.

Abstract

DSPG3, the human homolog to chick PG-Lb, is a mejrkp6of the small leucine-rich repeat proteoglycan (SLRP) family, including decorin, biglycan, fibromodulin, and lumican. In contrast to the tissue distribution of the other SLRPs, DSPG3 is predominantly expressed in cartilage. In this study, we have determined that the human DSPG3 gene is composed of seven exons: Exon 2 of DSPG3 includes the start codon, exons 4-7 code for the leucine-rich repeats, exons 3 and 7 contain the potential glycosaminoglycan attachment sites, and exon 7 contains the potential N-glycosylation sites and the stop codon. We have identified two polymorphic variations, an insertion/deletion composed of 19 nucleotides in intron 1 and a tetranucleotide (TATT)n repeat in intron 5. Analysis of 1.6 kb of upstream promoter sequence of DSPG3 reveals three TATA boxes, one of which is 20 nucleotides before the transcription start site. The transcription start site precedes the translation start site by 98 nucleotides. There are 14 potential binding sites for SOX9, a transcription factor present in cartilage, in the promoter, and in the first intron of DSPG3. We have examined the evolution of the SLRP gene family and found that gene products clustered together in the evolutionary tree are encoded by genes with similarities in genomic structure. Hence, it appears that the majority of the introns in the SLRP genes were inserted after the differentiation of the SLRP genes from an ancestral gene that was most likely composed of 2-3 exons.

Citing Articles

Epiphycan Predicts Poor Outcomes and Promotes Metastasis in Ovarian Cancer.

Deng L, Wang D, Chen S, Hu W, Zhang R Front Oncol. 2021; 11:653782.

PMID: 34888227 PMC: 8650094. DOI: 10.3389/fonc.2021.653782.

Transcriptome analysis identifies genes involved with the development of umbilical hernias in pigs.

Souza M, Ibelli A, Savoldi I, Cantao M, Peixoto J, Mores M PLoS One. 2020; 15(5):e0232542.

PMID: 32379844 PMC: 7205231. DOI: 10.1371/journal.pone.0232542.

Posterior amorphous corneal dystrophy is associated with a deletion of small leucine-rich proteoglycans on chromosome 12.

Kim M, Frausto R, Rosenwasser G, Bui T, Le D, Stone E PLoS One. 2014; 9(4):e95037.

PMID: 24759697 PMC: 3997350. DOI: 10.1371/journal.pone.0095037.

An evaluation of OPTC and EPYC as candidate genes for high myopia.

Wang P, Li S, Xiao X, Guo X, Zhang Q Mol Vis. 2009; 15:2045-9.

PMID: 19844586 PMC: 2763122.

References

Shinomura T, Kimata K . Proteoglycan-Lb, a small dermatan sulfate proteoglycan expressed in embryonic chick epiphyseal cartilage, is structurally related to osteoinductive factor. J Biol Chem. 1992; 267(2):1265-70. View

Grover J, Chen X, Korenberg J, Recklies A, Roughley P . The gene organization, chromosome location, and expression of a 55-kDa matrix protein (PRELP) of human articular cartilage. Genomics. 1996; 38(2):109-17. DOI: 10.1006/geno.1996.0605. View

Madisen L, Neubauer M, Plowman G, Rosen D, Segarini P, Dasch J . Molecular cloning of a novel bone-forming compound: osteoinductive factor. DNA Cell Biol. 1990; 9(5):303-9. DOI: 10.1089/dna.1990.9.303. View

Xu J, Radhakrishnamurthy B, Srinivasan S, Berenson G . Primary structure of bovine aorta biglycan core protein deduced from cloned CDNA. Biochem Mol Biol Int. 1995; 37(2):263-72. View

Traupe H, van den Ouweland A, van Oost B, Vogel W, Vetter U, Warren S . Fine mapping of the human biglycan (BGN) gene within the Xq28 region employing a hybrid cell panel. Genomics. 1992; 13(2):481-3. DOI: 10.1016/0888-7543(92)90279-2. View

Blochberger T, Vergnes J, Hempel J, Hassell J . cDNA to chick lumican (corneal keratan sulfate proteoglycan) reveals homology to the small interstitial proteoglycan gene family and expression in muscle and intestine. J Biol Chem. 1992; 267(1):347-52. View

Li W, Vergnes J, Cornuet P, Hassell J . cDNA clone to chick corneal chondroitin/dermatan sulfate proteoglycan reveals identity to decorin. Arch Biochem Biophys. 1992; 296(1):190-7. DOI: 10.1016/0003-9861(92)90562-b. View

Heinegard D, Oldberg A . Structure and biology of cartilage and bone matrix noncollagenous macromolecules. FASEB J. 1989; 3(9):2042-51. DOI: 10.1096/fasebj.3.9.2663581. View

Chakravarti S, Stallings R, Sundarraj N, Cornuet P, Hassell J . Primary structure of human lumican (keratan sulfate proteoglycan) and localization of the gene (LUM) to chromosome 12q21.3-q22. Genomics. 1995; 27(3):481-8. DOI: 10.1006/geno.1995.1080. View

10.

Wagner T, Wirth J, Meyer J, Zabel B, Held M, Zimmer J . Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell. 1994; 79(6):1111-20. DOI: 10.1016/0092-8674(94)90041-8. View

11.

Krusius T, Ruoslahti E . Primary structure of an extracellular matrix proteoglycan core protein deduced from cloned cDNA. Proc Natl Acad Sci U S A. 1986; 83(20):7683-7. PMC: 386785. DOI: 10.1073/pnas.83.20.7683. View

12.

Johnson H, Rosenberg L, Choi H, GARZA S, Hook M, Neame P . Characterization of epiphycan, a small proteoglycan with a leucine-rich repeat core protein. J Biol Chem. 1997; 272(30):18709-17. DOI: 10.1074/jbc.272.30.18709. View

13.

FOSTER J, Guioli S, Kwok C, Weller P, Stevanovic M, Weissenbach J . Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene. Nature. 1994; 372(6506):525-30. DOI: 10.1038/372525a0. View

14.

Danielson K, Fazzio A, Cohen I, Cannizzaro L, Eichstetter I, Iozzo R . The human decorin gene: intron-exon organization, discovery of two alternatively spliced exons in the 5' untranslated region, and mapping of the gene to chromosome 12q23. Genomics. 1993; 15(1):146-60. DOI: 10.1006/geno.1993.1022. View

15.

Funderburgh J, Funderburgh M, Hevelone N, Stech M, Justice M, Liu C . Sequence, molecular properties, and chromosomal mapping of mouse lumican. Invest Ophthalmol Vis Sci. 1995; 36(11):2296-303. View

16.

Thomas J, Sweetman W, Cresswell C, Wallis G, Grant M, Boot-Handford R . Sequence comparison of three mammalian type-X collagen promoters and preliminary functional analysis of the human promoter. Gene. 1995; 160(2):291-6. DOI: 10.1016/0378-1119(95)00189-d. View

17.

Sztrolovics R, Chen X, Grover J, Roughley P, Korenberg J . Localization of the human fibromodulin gene (FMOD) to chromosome 1q32 and completion of the cDNA sequence. Genomics. 1994; 23(3):715-7. DOI: 10.1006/geno.1994.1567. View

18.

Sudbeck P, Schmitz M, Baeuerle P, Scherer G . Sex reversal by loss of the C-terminal transactivation domain of human SOX9. Nat Genet. 1996; 13(2):230-2. DOI: 10.1038/ng0696-230. View

19.

Funderburgh J, Funderburgh M, Brown S, Vergnes J, Hassell J, Mann M . Sequence and structural implications of a bovine corneal keratan sulfate proteoglycan core protein. Protein 37B represents bovine lumican and proteins 37A and 25 are unique. J Biol Chem. 1993; 268(16):11874-80. View

20.

Oldberg A, Antonsson P, LINDBLOM K, Heinegard D . A collagen-binding 59-kd protein (fibromodulin) is structurally related to the small interstitial proteoglycans PG-S1 and PG-S2 (decorin). EMBO J. 1989; 8(9):2601-4. PMC: 401265. DOI: 10.1002/j.1460-2075.1989.tb08399.x. View