SDC4

SDC4
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases SDC4, SYND4, syndecan 4
External IDs MGI: 1349164 HomoloGene: 31121 GeneCards: SDC4
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez

6385

20971

Ensembl

ENSG00000124145

ENSMUSG00000017009

UniProt

P31431

O35988

RefSeq (mRNA)

NM_002999

NM_011521

RefSeq (protein)

NP_002990.2

NP_035651.1

Location (UCSC) Chr 20: 45.33 – 45.35 Mb Chr 2: 164.42 – 164.44 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

Syndecan-4 is a protein that in humans is encoded by the SDC4 gene.[3][4] Syndecan-4 is one of the four vertebrate syndecans and has a molecular weight of ~20 kDa. Syndecans are the best-characterized plasma membrane proteoglycans. Their intracellular domain of membrane-spanning core protein interacts with actin cytoskeleton and signaling molecules in the cell cortex. Syndecans are normally found on the cell surface of fibroblasts and epithelial cells. Syndecans interact with fibronectin on the cell surface, cytoskeletal and signaling proteins inside the cell to modulate the function of integrin in cell-matrix adhesion. Also, syndecans bind to FGFs and bring them to the FGF receptor on the same cell. As a co-receptor or regulator, mutated certain proteoglycans could cause severe developmental defects, like disordered distribution or inactivation of signaling molecules.

Syndecans have similar structural features:

Syndecans normally form homodimers or multimers. Their biological function includes cell growth regulation, differentiation, and adhesion. Syndecan-4 has more widespread distribution than other syndecans and it is the only syndecan that has been found consistently in focal adhesions.[5]

Gene

Syndecan-4 is also called ryudocan or amphiglycan. It is found on chromosome 20, while a pseudogene has been found on chromosome 22.[6] Syndecan-4 is one of the four vertebrate syndecans and has a molecular weight of ~20 kDa. It has more widespread distribution than other syndecans, and it is the only syndecan that has been found consistently in focal adhesions.[7]

Function

Syndecan-4 is a transmembrane (type I) heparan sulfate proteoglycan that functions as a receptor in intracellular signaling. The protein is found as a homodimer and is a member of the syndecan proteoglycan family.[6] Syndecan-4 interacts with extracellular matrix, anticoagulants, and growth-factors. It also regulates the actin cytoskeleton, cell adhesion, and cell migration.[8]

Syndecan-4 activates protein kinase C (PKC), an enzyme involved in signal transduction.[9] The variable domain of syndecan-4 could be a site of self-association. The degree of oligomerization correlates with the activity of kinases, so the degree of clustering of syndecan-4 correlates to PKC activity.[10] Syndecan-4 also binds to phosphatidylinositol (4,5)-bisphosphate (PIP2) through the variable domain and increases PKC activity ten-fold.[11]

Syndecan-4 is also a regulator of fibroblast growth factor-2 (FGF-2) signaling. Syndecan-4 binds to FGF and mediates interaction with the FGF receptor.[12] Because the tight correlation between syndecan-4 and growth factors, the efficiency of angiogenic therapies have been thought to relate to syndecan-4. Growth factor signaling may be disrupted by changes in syndecan-4 expression.[13][14][15] The cellular uptake, trafficking, and nuclear localization of FGF-2 could be increased by co-delivery of syndecan-4 proteoliposomes. These alterations should be considered in FGF-2-based therapies.[16]

Syndecan-4 is also associated with the healing process. Lack of Sdc4 gene causes delayed wound healing in mice. This delay may be due to compromised fibroblast motility.[17]

Clinical significance

Osteoarthritis

Syndecan-4 is upregulated in osteoarthritis and inhibition of syndecan-4 reduces cartilage destruction in mouse models of OA.[18]

See Sindecán-4 at the Spanish Wikipedia

References

  1. "Human PubMed Reference:".
  2. "Mouse PubMed Reference:".
  3. Kojima T, Inazawa J, Takamatsu J, Rosenberg RD, Saito H (Mar 1993). "Human ryudocan core protein: molecular cloning and characterization of the cDNA, and chromosomal localization of the gene". Biochem Biophys Res Commun. 190 (3): 814–22. doi:10.1006/bbrc.1993.1122. PMID 7916598.
  4. David G, van der Schueren B, Marynen P, Cassiman JJ, van den Berghe H (Sep 1992). "Molecular cloning of amphiglycan, a novel integral membrane heparan sulfate proteoglycan expressed by epithelial and fibroblastic cells". J Cell Biol. 118 (4): 961–9. doi:10.1083/jcb.118.4.961. PMC 2289559Freely accessible. PMID 1500433.
  5. Woods A, Couchman JR (1994). "Syndecan 4 heparan sulfate proteoglycan is a selectively enriched and widespread focal adhesion component". Mol Biol Cell. 5 (2): 183–192. doi:10.1091/mbc.5.2.183. PMC 301024Freely accessible. PMID 8019004.
  6. 1 2 "Entrez Gene: SDC4 syndecan 4".
  7. Woods A, Couchman JR (February 1994). "Syndecan 4 heparan sulfate proteoglycan is a selectively enriched and widespread focal adhesion component". Mol. Biol. Cell. 5 (2): 183–92. doi:10.1091/mbc.5.2.183. PMC 301024Freely accessible. PMID 8019004.
  8. Woods A, Couchman JR (May 1998). "Syndecans: synergistic activators of cell adhesion". Trends Cell Biol. 8 (5): 189–92. doi:10.1016/S0962-8924(98)01244-6. PMID 9695837.
  9. Hyatt SL, Klauck T, Jaken S (1990). "Protein kinase C is localized in focal contacts of normal but not transformed fibroblasts". Mol. Carcinog. 3 (2): 45–53. doi:10.1002/mc.2940030202. PMID 2161238.
  10. Grootjans JJ, Zimmermann P, Reekmans G, Smets A, Degeest G, Dürr J, David G (December 1997). "Syntenin, a PDZ protein that binds syndecan cytoplasmic domains". Proc. Natl. Acad. Sci. U.S.A. 94 (25): 13683–8. Bibcode:1997PNAS...9413683G. doi:10.1073/pnas.94.25.13683. PMC 28366Freely accessible. PMID 9391086.
  11. Oh ES, Woods A, Couchman JR (May 1997). "Multimerization of the cytoplasmic domain of syndecan-4 is required for its ability to activate protein kinase C". J. Biol. Chem. 272 (18): 11805–11. doi:10.1074/jbc.272.18.11805. PMID 9115237.
  12. Chua CC, Rahimi N, Forsten-Williams K, Nugent MA (February 2004). "Heparan sulfate proteoglycans function as receptors for fibroblast growth factor-2 activation of extracellular signal-regulated kinases 1 and 2". Circ. Res. 94 (3): 316–23. doi:10.1161/01.RES.0000112965.70691.AC. PMID 14684627.
  13. Bortoff KD, Wagner WD (February 2005). "Reduced syndecan-4 expression in arterial smooth muscle cells with enhanced proliferation". Exp. Mol. Pathol. 78 (1): 10–6. doi:10.1016/j.yexmp.2004.08.010. PMID 15596055.
  14. Neelapu SS, Gause BL, Harvey L, Lee ST, Frye AR, Horton J, Robb RJ, Popescu MC, Kwak LW (June 2007). "A novel proteoliposomal vaccine induces antitumor immunity against follicular lymphoma". Blood. 109 (12): 5160–3. doi:10.1182/blood-2006-12-063594. PMC 1941785Freely accessible. PMID 17339422.
  15. Olsson U, Bondjers G, Camejo G (March 1999). "Fatty acids modulate the composition of extracellular matrix in cultured human arterial smooth muscle cells by altering the expression of genes for proteoglycan core proteins". Diabetes. 48 (3): 616–22. doi:10.2337/diabetes.48.3.616. PMID 10078565.
  16. Jang E, Albadawi H, Watkins MT, Edelman ER, Baker AB (January 2012). "Syndecan-4 proteoliposomes enhance fibroblast growth factor-2 (FGF-2)-induced proliferation, migration, and neovascularization of ischemic muscle". Proc. Natl. Acad. Sci. U.S.A. 109 (5): 1679–84. Bibcode:2012PNAS..109.1679J. doi:10.1073/pnas.1117885109. PMC 3277125Freely accessible. PMID 22307630.
  17. Echtermeyer F, Streit M, Wilcox-Adelman S, Saoncella S, Denhez F, Detmar M, Goetinck P (January 2001). "Delayed wound repair and impaired angiogenesis in mice lacking syndecan-4". J. Clin. Invest. 107 (2): R9–R14. doi:10.1172/JCI10559. PMC 199172Freely accessible. PMID 11160142.
  18. Hass MJ (Sep 2009). "SDC4: OA joint effort". SciBX. 2 (34). doi:10.1038/scibx.2009.1297.

Further reading

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