Biglycan

Biglycan is a small leucine-rich repeat proteoglycan (SLRP) which is found in a variety of extracellular matrix tissues, including bone, cartilage and tendon. In humans, biglycan is encoded by the BGN gene^[5] which is located on the X chromosome.

BGN
Identifiers
Aliases	BGN, DSPG1, PG-S1, PGI, SLRR1A, biglycan, SEMDX, MRLS
External IDs	OMIM: 301870; MGI: 88158; HomoloGene: 1293; GeneCards: BGN; OMA:BGN - orthologs
Gene location (Human) Chr. X chromosome (human)[1] Band Xq28 Start 153,494,980 bp[1] End 153,509,546 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X A7.3|X 37.33 cM Start 72,527,208 bp[2] End 72,539,539 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Descending thoracic aorta ascending aorta right coronary artery tendon of biceps brachii popliteal artery tibial arteries left coronary artery tibia right lung gallbladder Top expressed in calvaria tunica media of zone of aorta stroma of bone marrow ascending aorta ankle joint umbilical cord body of femur aortic valve ankle molar More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein kinase inhibitor activity glycosaminoglycan binding extracellular matrix structural constituent extracellular matrix binding extracellular matrix structural constituent conferring compression resistance protein binding Cellular component cytoplasm extracellular matrix intracellular anatomical structure transport vesicle cell surface lysosomal lumen Golgi lumen sarcolemma extracellular exosome extracellular space extracellular region collagen-containing extracellular matrix Biological process glycosaminoglycan metabolic process negative regulation of protein kinase activity cytokine-mediated signaling pathway chondroitin sulfate biosynthetic process extracellular matrix organization blood vessel remodeling chondroitin sulfate catabolic process peptide cross-linking via chondroitin 4-sulfate glycosaminoglycan dermatan sulfate biosynthetic process negative regulation of receptor signaling pathway via JAK-STAT biological process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 633 12111 Ensembl ENSG00000182492 ENSMUSG00000031375 UniProt P21810 P28653 RefSeq (mRNA) NM_001711 NM_007542 RefSeq (protein) NP_001702 NP_031568 Location (UCSC) Chr X: 153.49 – 153.51 Mb Chr X: 72.53 – 72.54 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The name "biglycan" was proposed in an article by Fisher, Termine and Young in an article in the Journal of Biological Chemistry in 1989 because the proteoglycan contained two GAG chains; formerly it was known as proteoglycan-I (PG-I).^[6]

Structure

Biglycan consists of a protein core containing leucine-rich repeat regions and two glycosaminoglycan (GAG) chains consisting of either chondroitin sulfate (CS) or dermatan sulfate (DS), with DS being more abundant in most connective tissues. The CS/DS chains are attached at amino acids 5 and 10 in human biglycan.^[7] The composition of the GAG chains has been reported as varying according to tissue of origin. Non-glycanated forms of biglycan (no GAG chains) increase with age in human articular cartilage.^[8]

The composition of GAG chains of biglycan and decorin originating from the same tissue has been reported to be similar.^[9]

The structure of biglycan core protein is highly conserved across species; over 90% homology has been reported for rat, mouse, bovine and human biglycan core proteins.

Function

Biglycan is believed to play a role in the mineralization of bone. Knock-out mice that have had the gene for biglycan suppressed (Bgn -/-) have an osteoporosis-like phenotype with reduced growth rate and lower bone mass than mice that can express biglycan.^[10]

Biglycan core protein binds to the growth factors BMP-4 and influences its bioactivity.^[11] It has also been reported that the presence of biglycan is necessary for BMP-4 to exert its effects on osteoblasts.^[12] There is also evidence that biglycan binds to TGF-beta 1.

Interactions

Biglycan interacts with collagen, both via the core protein and GAG chains.^[13][14] It has been reported that biglycan interacts more strongly with collagen type II than collagen type I.^[15][16] Biglycan has been reported to compete with decorin for the same binding site on collagen.^[13]

Biglycan has been shown to interact with SGCA.^[17]

Biglycan is a particularly important proteoglycan for binding to lipoprotein in human blood vessels, thus being a significant cause of atherosclerosis.^[18]

References

1. GRCh38: Ensembl release 89: ENSG00000182492 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031375 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Traupe H, van den Ouweland AM, van Oost BA, Vogel W, Vetter U, Warren ST, Rocchi M, Darlison MG, Ropers HH (June 1992). "Fine mapping of the human biglycan (BGN) gene within the Xq28 region employing a hybrid cell panel". Genomics. 13 (2): 481–3. doi:10.1016/0888-7543(92)90279-2. PMID 1612609.
6. Fisher LW, Termine JD, Young MF (March 1989). "Deduced protein sequence of bone small proteoglycan I (biglycan) shows homology with proteoglycan II (decorin) and several nonconnective tissue proteins in a variety of species". J. Biol. Chem. 264 (8): 4571–6. doi:10.1016/S0021-9258(18)83781-4. PMID 2647739.
7. Roughley PJ, White RJ (September 1989). "Dermatan sulphate proteoglycans of human articular cartilage. The properties of dermatan sulphate proteoglycans I and II". Biochem. J. 262 (3): 823–7. doi:10.1042/bj2620823. PMC 1133347. PMID 2590169.
8. Roughley PJ, White RJ, Magny MC, Liu J, Pearce RH, Mort JS (October 1993). "Non-proteoglycan forms of biglycan increase with age in human articular cartilage". Biochem. J. 295 (2): 421–6. doi:10.1042/bj2950421. PMC 1134898. PMID 8240239.
9. Cheng F, Heinegård D, Malmström A, Schmidtchen A, Yoshida K, Fransson LA (October 1994). "Patterns of uronosyl epimerization and 4-/6-O-sulphation in chondroitin/dermatan sulphate from decorin and biglycan of various bovine tissues". Glycobiology. 4 (5): 685–96. doi:10.1093/glycob/4.5.685. PMID 7881183.
10. Xu T, Bianco P, Fisher LW, Longenecker G, Smith E, Goldstein S, Bonadio J, Boskey A, Heegaard AM, Sommer B, Satomura K, Dominguez P, Zhao C, Kulkarni AB, Robey PG, Young MF (September 1998). "Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice". Nature Genetics. 20 (1): 78–82. doi:10.1038/1746. PMID 9731537. S2CID 8383857.
11. Moreno M, Muñoz R, Aroca F, Labarca M, Brandan E, Larraín J (April 2005). "Biglycan is a new extracellular component of the Chordin-BMP4 signaling pathway". EMBO J. 24 (7): 1397–405. doi:10.1038/sj.emboj.7600615. PMC 1142540. PMID 15775969.
12. Chen XD, Fisher LW, Robey PG, Young MF (June 2004). "The small leucine-rich proteoglycan biglycan modulates BMP-4-induced osteoblast differentiation". FASEB J. 18 (9): 948–58. doi:10.1096/fj.03-0899com. PMID 15173106. S2CID 30042377.
13. Schönherr E, Witsch-Prehm P, Harrach B, Robenek H, Rauterberg J, Kresse H (February 1995). "Interaction of biglycan with type I collagen". J. Biol. Chem. 270 (6): 2776–83. doi:10.1074/jbc.270.6.2776. PMID 7852349.
14. Pogány G, Hernandez DJ, Vogel KG (August 1994). "The in vitro interaction of proteoglycans with type I collagen is modulated by phosphate". Archives of Biochemistry and Biophysics. 313 (1): 102–11. doi:10.1006/abbi.1994.1365. PMID 8053669.
15. Vynios DH, Papageorgakopoulou N, Sazakli H, Tsiganos CP (September 2001). "The interactions of cartilage proteoglycans with collagens are determined by their structures". Biochimie. 83 (9): 899–906. doi:10.1016/S0300-9084(01)01332-3. PMID 11698112.
16. Bidanset DJ, Guidry C, Rosenberg LC, Choi HU, Timpl R, Hook M (March 1992). "Binding of the proteoglycan decorin to collagen type VI". J. Biol. Chem. 267 (8): 5250–6. doi:10.1016/S0021-9258(18)42759-7. PMID 1544908.^{[permanent dead link‍]}
17. Bowe MA, Mendis DB, Fallon JR (2000). "The small leucine-rich repeat proteoglycan biglycan binds to alpha-dystroglycan and is upregulated in dystrophic muscle". J. Cell Biol. 148 (4): 801–10. doi:10.1083/jcb.148.4.801. PMC 2169361. PMID 10684260.
18. Fogelstrand P, Borén J (2012). "Retention of atherogenic lipoproteins in the artery wall and its role in atherogenesis". Nutrition, Metabolism, and Cardiovascular Diseases. 22 (1): 1–7. doi:10.1016/j.numecd.2011.09.007. PMID 22176921.

External links

• biglycan at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Human BGN genome location and BGN gene details page in the UCSC Genome Browser.