Syndecan-4

SDC4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1EJP, 1EJQ, 1OBY, 1YBO
Identifiers
Aliases	SDC4, SYND4, syndecan 4
External IDs	MGI: 1349164 HomoloGene: 31121 GeneCards: SDC4
Gene location (Human) Chr. Chromosome 20 (human)[1] Band No data available Start 45,325,288 bp[1] End 45,348,424 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band No data available Start 164,424,247 bp[2] End 164,443,887 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • fibronectin binding • protein binding • thrombospondin receptor activity • protein kinase C binding Cellular component • integral component of membrane • membrane • focal adhesion • plasma membrane • integral component of plasma membrane • extracellular region • lysosomal lumen • Golgi lumen • membrane raft • costamere • extracellular exosome • cell surface Biological process • glycosaminoglycan metabolic process • ureteric bud development • inner ear receptor stereocilium organization • positive regulation of extracellular exosome assembly • wound healing • retinoid metabolic process • neural tube closure • glycosaminoglycan catabolic process • glycosaminoglycan biosynthetic process • positive regulation of focal adhesion assembly • positive regulation of exosomal secretion • regulation of fibroblast migration • positive regulation of stress fiber assembly • positive regulation of protein kinase activity • signal transduction • negative regulation of T cell proliferation • leukocyte migration • cell migration Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6385	20971
Ensembl	ENSG00000124145	ENSMUSG00000017009
UniProt	P31431	O35988
RefSeq (mRNA)	NM_002999	NM_011521
RefSeq (protein)	NP_002990	NP_035651
Location (UCSC)	Chr 20: 45.33 – 45.35 Mb	Chr 20: 164.42 – 164.44 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Syndecan-4 is a protein that in humans is encoded by the SDC4 gene.^[5][6] 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:

• Attach to heparan sulfate chains – interacting factors (e.g. Matrix molecules, growth factors, and enzymes)
• Chondroitin sulfate chain
• Transmembrane domain – self-association
• C1 domain – actin-association cytoskeleton
• Variable domain – syndecan-specific
• C2 domain – attach to PDZ proteins

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.^[7]

Gene

Syndecan-4 is also called ryudocan or amphiglycan. It is found on chromosome 20, while a pseudogene has been found on chromosome 22.^[8] 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.^[9]

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.^[8] Syndecan-4 interacts with extracellular matrix, anticoagulants, and growth-factors. It also regulates the actin cytoskeleton, cell adhesion, and cell migration.^[10]

Syndecan-4 activates protein kinase C (PKC), an enzyme involved in signal transduction.^[11] 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.^[12] Syndecan-4 also binds to phosphatidylinositol (4,5)-bisphosphate (PIP2) through the variable domain and increases PKC activity ten-fold.^[13]

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.^[14] 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.^[15][16][17] 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.^[18]

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.^[19]

Clinical significance

Osteoarthritis

Syndecan-4 is upregulated in osteoarthritis and inhibition of syndecan-4 reduces cartilage destruction in mouse models of OA.^[20]

See Sindecán-4 at the Spanish Wikipedia

References

Further reading