Decorin

Last updated
DCN
Protein DCN PDB 1xcd.png
Identifiers
Aliases DCN , Dcn, DC, DSPG2, PG40, PGII, PGS2, SLRR1B, mDcn, CSCD, decorin
External IDs OMIM: 125255 MGI: 94872 HomoloGene: 22430 GeneCards: DCN
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001190451
NM_007833

RefSeq (protein)

NP_001177380
NP_031859

Location (UCSC) Chr 12: 91.14 – 91.18 Mb Chr 10: 97.32 – 97.35 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Decorin is a protein that in humans is encoded by the DCN gene.

Contents

Decorin is a proteoglycan that is on average 90 - 140 kilodaltons (kDa) in molecular weight. It belongs to the small leucine-rich proteoglycan (SLRP) family and consists of a protein core containing leucine repeats with a glycosaminoglycan (GAG) chain consisting of either chondroitin sulfate (CS) or dermatan sulfate (DS).

Decorin is a small cellular or pericellular matrix proteoglycan and is closely related in structure to biglycan protein. Decorin and biglycan are thought to be the result of a gene duplication. This protein is a component of connective tissue, binds to type I collagen fibrils, and plays a role in matrix assembly. [5]

Naming

Decorin's name is a derivative of both the fact that it "decorates" collagen type I, and that it interacts with the "d" and "e" bands of fibrils of this collagen.

Function

Decorin appears to influence fibrillogenesis, and also interacts with fibronectin, thrombospondin, the complement component C1q, epidermal growth factor receptor (EGFR) and transforming growth factor-beta (TGF-beta).

Decorin has been shown to either enhance or inhibit the activity of TGF-beta 1. The primary function of decorin involves regulation during the cell cycle.

It has been involved in the regulation of autophagy, of endothelial cell and inhibits angiogenesis. This process is mediated by a high-affinity interaction with VEGFR2 (vascular endothelial growth factor receptor) which leads to increased levels of tumor suppressor gene called PEG3. [6] Other angiogenic growth factors that decorin inhibits are angiopoietin, hepatocyte growth factor (HGF) and platelet-derived growth factor (PDGF). [7]

Decorin has recently been established as a myokine. In this role, it promotes muscle hypertrophy by binding with myostatin. [8]

Clinical significance

Keloid scars have decreased decorin expression compared to healthy skin. [9] Development of congenital stromal corneal dystrophy is dependent on export and extracellular deposition of truncated decorin. [10]

Animal studies

Infusion of decorin into experimental rodent spinal cord injuries has been shown to suppress scar formation and promote axon growth.

Decorin has been shown to have anti-tumorigenic properties in an experimental murine tumor model and is capable of suppressing the growth of various tumor cell lines. [11] The decorin-deficient knockout mouse shows reduced inflammatory reactions during contact dermatitis due to a defect in leukocyte recruitment and altered interferon gamma function. [12] [13]

Interactions

Decorin has been shown to interact with:

Related Research Articles

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Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. It is approved for marketing as a topical solution in India by Central Drugs Standard Control organization in 2020 under the brand name FIBREGA for chronic wounds. Fibronectin also binds to other extracellular matrix proteins such as collagen, fibrin, and heparan sulfate proteoglycans.

<span class="mw-page-title-main">Proteoglycan</span> Class of compounds

Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge. The Ser residue is generally in the sequence -Ser-Gly-X-Gly-, although not every protein with this sequence has an attached glycosaminoglycan. The chains are long, linear carbohydrate polymers that are negatively charged under physiological conditions due to the occurrence of sulfate and uronic acid groups. Proteoglycans occur in connective tissue.

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Versican is a large extracellular matrix proteoglycan that is present in a variety of human tissues. It is encoded by the VCAN gene.

<span class="mw-page-title-main">Perlecan</span>

Perlecan (PLC) also known as basement membrane-specific heparan sulfate proteoglycan core protein (HSPG) or heparan sulfate proteoglycan 2 (HSPG2), is a protein that in humans is encoded by the HSPG2 gene. The HSPG2 gene codes for a 4,391 amino acid protein with a molecular weight of 468,829. It is one of the largest known proteins. The name perlecan comes from its appearance as a "string of pearls" in rotary shadowed images.

<span class="mw-page-title-main">Heparan sulfate</span> Macromolecule

Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins. In this form, HS binds to a variety of protein ligands, including Wnt, and regulates a wide range of biological activities, including developmental processes, angiogenesis, blood coagulation, abolishing detachment activity by GrB, and tumour metastasis. HS has also been shown to serve as cellular receptor for a number of viruses, including the respiratory syncytial virus. One study suggests that cellular heparan sulfate has a role in SARS-CoV-2 Infection, particularly when the virus attaches with ACE2.

<span class="mw-page-title-main">TGF beta 1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Biglycan</span> Protein-coding gene in humans

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 which is located on the X chromosome.

<span class="mw-page-title-main">TGF beta 2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">TGFBR3</span> Protein-coding gene in the species Homo sapiens

Betaglycan also known as Transforming growth factor beta receptor III (TGFBR3), is a cell-surface chondroitin sulfate / heparan sulfate proteoglycan >300 kDa in molecular weight. Betaglycan binds to various members of the TGF-beta superfamily of ligands via its core protein, and bFGF via its heparan sulfate chains. TGFBR3 is the most widely expressed type of TGF-beta receptor. Its affinity towards all individual isoforms of TGF-beta is similarly high and therefore it plays an important role as a coreceptor mediating the binding of TGF-beta to its other receptors - specifically TGFBR2. The intrinsic kinase activity of this receptor has not yet been described. In regard of TGF-beta signalling it is generally considered a non-signaling receptor or a coreceptor. By binding to various member of the TGF-beta superfamily at the cell surface it acts as a reservoir of TGF-beta.

<span class="mw-page-title-main">Syndecan 1</span> Protein which in humans is encoded by the SDC1 gene

Syndecan 1 is a protein which in humans is encoded by the SDC1 gene. The protein is a transmembrane heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecan-1 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Syndecan-1 is a sponge for growth factors and chemokines, with binding largely via heparan sulfate chains. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein.

<span class="mw-page-title-main">FBLN1</span> Protein-coding gene in the species Homo sapiens

FBLN1 is the gene encoding fibulin-1, an extracellular matrix and plasma protein.

<span class="mw-page-title-main">Transforming growth factor, beta 3</span> Protein-coding gene in the species Homo sapiens

Transforming growth factor beta-3 is a protein that in humans is encoded by the TGFB3 gene.

<span class="mw-page-title-main">Integrin beta 6</span> Protein-coding gene in the species Homo sapiens

Integrin beta-6 is a protein that in humans is encoded by the ITGB6 gene. It is the β6 subunit of the integrin αvβ6. Integrins are αβ heterodimeric glycoproteins which span the cell’s membrane, integrating the outside and inside of the cell. Integrins bind to specific extracellular proteins in the extracellular matrix or on other cells and subsequently transduce signals intracellularly to affect cell behaviour. One α and one β subunit associate non-covalently to form 24 unique integrins found in mammals. While some β integrin subunits partner with multiple α subunits, β6 associates exclusively with the αv subunit. Thus, the function of ITGB6 is entirely associated with the integrin αvβ6.

<span class="mw-page-title-main">Collagen, type IV, alpha 6</span> Mammalian protein found in humans

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<span class="mw-page-title-main">Serglycin</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Lumican</span>

Lumican, also known as LUM, is an extracellular matrix protein that, in humans, is encoded by the LUM gene on chromosome 12.

<span class="mw-page-title-main">Collagen, type XIV, alpha 1</span> Protein found in humans

Collagen alpha-1(XIV) chain is a protein that in humans is encoded by the COL14A1 gene. It likely plays a role in collagen binding and cell-cell adhesion.

<span class="mw-page-title-main">Fibromodulin</span> Protein

Fibromodulin is a protein that in humans is encoded by the FMOD gene.

<span class="mw-page-title-main">B4GALT7</span> Protein-coding gene in the species Homo sapiens

Beta-1,4-galactosyltransferase 7 also known as galactosyltransferase I is an enzyme that in humans is encoded by the B4GALT7 gene. Galactosyltransferase I catalyzes the synthesis of the glycosaminoglycan-protein linkage in proteoglycans. Proteoglycans in turn are structural components of the extracellular matrix that is found between cells in connective tissues.

<span class="mw-page-title-main">Dermatopontin</span> Protein-coding gene in the species Homo sapiens

Dermatopontin also known as tyrosine-rich acidic matrix protein (TRAMP) is a protein that in humans is encoded by the DPT gene. Dermatopontin is a 22-kDa protein of the noncollagenous extracellular matrix (ECM) estimated to comprise 12 mg/kg of wet dermis weight. To date, homologues have been identified in five different mammals and 12 different invertebrates with multiple functions. In vertebrates, the primary function of dermatopontin is a structural component of the ECM, cell adhesion, modulation of TGF-β activity and cellular quiescence). It also has pathological involvement in heart attacks and decreased expression in leiomyoma and fibrosis. In invertebrate, dermatopontin homologue plays a role in hemagglutination, cell-cell aggregation, and expression during parasite infection.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000011465 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000019929 - 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. "Entrez Gene: DCN decorin".
  6. Buraschi S, Neill T, Goyal A, Poluzzi C, Smythies J, Owens RT, et al. (July 2013). "Decorin causes autophagy in endothelial cells via Peg3". Proceedings of the National Academy of Sciences of the United States of America. 110 (28): E2582-91. Bibcode:2013PNAS..110E2582B. doi: 10.1073/pnas.1305732110 . PMC   3710796 . PMID   23798385.
  7. Järveläinen H, Sainio A, Wight TN (April 2015). "Pivotal role for decorin in angiogenesis". Matrix Biology. 43: 15–26. doi:10.1016/j.matbio.2015.01.023. PMC   4560244 . PMID   25661523.
  8. Kanzleiter T, Rath M, Görgens SW, Jensen J, Tangen DS, Kolnes AJ, et al. (July 2014). "The myokine decorin is regulated by contraction and involved in muscle hypertrophy". Biochemical and Biophysical Research Communications. 450 (2): 1089–94. doi:10.1016/j.bbrc.2014.06.123. PMID   24996176.
  9. Jumper N, Paus R, Bayat A (September 2015). "Functional histopathology of keloid disease". Histology and Histopathology. 30 (9): 1033–57. doi:10.14670/HH-11-624. PMID   25900252.
  10. Mellgren AE, Bruland O, Vedeler A, Saraste J, Schönheit J, Bredrup C, et al. (May 2015). "Development of congenital stromal corneal dystrophy is dependent on export and extracellular deposition of truncated decorin". Investigative Ophthalmology & Visual Science. 56 (5): 2909–15. doi:10.1167/iovs.14-16014. PMID   26029887.
  11. Sofeu Feugaing DD, Götte M, Viola M (January 2013). "More than matrix: the multifaceted role of decorin in cancer". European Journal of Cell Biology. 92 (1): 1–11. doi:10.1016/j.ejcb.2012.08.004. PMID   23058688.
  12. Seidler DG, Mohamed NA, Bocian C, Stadtmann A, Hermann S, Schäfers K, et al. (December 2011). "The role for decorin in delayed-type hypersensitivity". Journal of Immunology. 187 (11): 6108–19. doi:10.4049/jimmunol.1100373. PMC   5070385 . PMID   22043007.
  13. Bocian C, Urbanowitz AK, Owens RT, Iozzo RV, Götte M, Seidler DG (May 2013). "Decorin potentiates interferon-γ activity in a model of allergic inflammation". The Journal of Biological Chemistry. 288 (18): 12699–711. doi: 10.1074/jbc.M112.419366 . PMC   3642316 . PMID   23460644.
  14. 1 2 Schönherr E, Broszat M, Brandan E, Bruckner P, Kresse H (July 1998). "Decorin core protein fragment Leu155-Val260 interacts with TGF-beta but does not compete for decorin binding to type I collagen". Archives of Biochemistry and Biophysics. 355 (2): 241–8. doi:10.1006/abbi.1998.0720. PMID   9675033.
  15. Santra M, Reed CC, Iozzo RV (September 2002). "Decorin binds to a narrow region of the epidermal growth factor (EGF) receptor, partially overlapping but distinct from the EGF-binding epitope". The Journal of Biological Chemistry. 277 (38): 35671–81. doi: 10.1074/jbc.M205317200 . PMID   12105206. S2CID   20575381.
  16. Iozzo RV, Moscatello DK, McQuillan DJ, Eichstetter I (February 1999). "Decorin is a biological ligand for the epidermal growth factor receptor". The Journal of Biological Chemistry. 274 (8): 4489–92. doi: 10.1074/jbc.274.8.4489 . PMID   9988678. S2CID   32175802.
  17. Hildebrand A, Romarís M, Rasmussen LM, Heinegård D, Twardzik DR, Border WA, Ruoslahti E (September 1994). "Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta". The Biochemical Journal. 302 ( Pt 2) (2): 527–34. doi:10.1042/bj3020527. PMC   1137259 . PMID   8093006.
  18. Takeuchi Y, Kodama Y, Matsumoto T (December 1994). "Bone matrix decorin binds transforming growth factor-beta and enhances its bioactivity". The Journal of Biological Chemistry. 269 (51): 32634–8. doi: 10.1016/S0021-9258(18)31681-8 . PMID   7798269.
  19. 1 2 Merline R, Moreth K, Beckmann J, Nastase MV, Zeng-Brouwers J, Tralhão JG, et al. (November 2011). "Signaling by the matrix proteoglycan decorin controls inflammation and cancer through PDCD4 and MicroRNA-21". Science Signaling. 4 (199): ra75. doi:10.1126/scisignal.2001868. PMC   5029092 . PMID   22087031.

Further reading