Gene Symbol: Sdc4
Description: syndecan 4
Alias: AA959608, AW108331, Synd4, ryudocan, syndecan-4, syndecan-4, ryudocan core protein
Species: mouse
Products:     Sdc4

Top Publications

  1. Mahalingam Y, Gallagher J, Couchman J. Cellular adhesion responses to the heparin-binding (HepII) domain of fibronectin require heparan sulfate with specific properties. J Biol Chem. 2007;282:3221-30 pubmed
    ..Several separate, specific properties of cell surface HS are therefore required in cell adhesion responses to the fibronectin HepII domain. ..
  2. Ishiguro K, Kadomatsu K, Kojima T, Muramatsu H, Tsuzuki S, Nakamura E, et al. Syndecan-4 deficiency impairs focal adhesion formation only under restricted conditions. J Biol Chem. 2000;275:5249-52 pubmed
    ..When the signal is delivered as a substratum-bound form, other molecule(s) also participate(s) in the signal reception. ..
  3. Saoncella S, Calautti E, Neveu W, Goetinck P. Syndecan-4 regulates ATF-2 transcriptional activity in a Rac1-dependent manner. J Biol Chem. 2004;279:47172-6 pubmed
    ..Our results reveal a novel function for syndecan-4 in modulating nuclear transcriptional activity and indicate an underlying mechanism that acts at the level of Rac1-p38/JNK signaling. ..
  4. Echtermeyer F, Streit M, Wilcox Adelman S, Saoncella S, Denhez F, Detmar M, et al. Delayed wound repair and impaired angiogenesis in mice lacking syndecan-4. J Clin Invest. 2001;107:R9-R14 pubmed
    ..These results indicate that syndecan-4 is an important cell-surface receptor in wound healing and angiogenesis and that syndecan-4 is haplo-insufficient in these processes. ..
  5. Partovian C, Ju R, Zhuang Z, Martin K, Simons M. Syndecan-4 regulates subcellular localization of mTOR Complex2 and Akt activation in a PKCalpha-dependent manner in endothelial cells. Mol Cell. 2008;32:140-9 pubmed publisher
    ..Thus, S4-dependent targeting of PKCalpha to the plasma membrane is required for recruitment of mTORC2 components to the rafts and Akt activation. ..
  6. Iwabuchi T, Goetinck P. Syndecan-4 dependent FGF stimulation of mouse vibrissae growth. Mech Dev. 2006;123:831-41 pubmed
  7. Tkachenko E, Elfenbein A, Tirziu D, Simons M. Syndecan-4 clustering induces cell migration in a PDZ-dependent manner. Circ Res. 2006;98:1398-404 pubmed
  8. Dedkov E, Thomas M, Sonka M, Yang F, Chittenden T, Rhodes J, et al. Synectin/syndecan-4 regulate coronary arteriolar growth during development. Dev Dyn. 2007;236:2004-10 pubmed
    ..Moreover, our data reveal that gender influences the arteriolar growth response to syndecan-4 but not to synectin. ..
  9. Whiteford J, Ko S, Lee W, Couchman J. Structural and cell adhesion properties of zebrafish syndecan-4 are shared with higher vertebrates. J Biol Chem. 2008;283:29322-30 pubmed publisher
    ..Therefore, the cell adhesion properties of syndecan-4 are consistent across the vertebrate spectrum and reflect an early acquisition of specialization after syndecan gene duplication events at the invertebrate/early chordate boundary. ..

More Information


  1. Elfenbein A, Rhodes J, Meller J, Schwartz M, Matsuda M, Simons M. Suppression of RhoG activity is mediated by a syndecan 4-synectin-RhoGDI1 complex and is reversed by PKCalpha in a Rac1 activation pathway. J Cell Biol. 2009;186:75-83 pubmed publisher
    ..Its activity is partially mediated by binding to syndecan 4 (S4), a proteoglycan receptor...
  2. Wilcox Adelman S, Denhez F, Goetinck P. Syndecan-4 modulates focal adhesion kinase phosphorylation. J Biol Chem. 2002;277:32970-7 pubmed
    ..In addition, the data suggest that this pathway includes the negative regulation of a protein-tyrosine phosphatase. Our results implicate syndecan-4 activation in a direct role in focal adhesion regulation. ..
  3. Echtermeyer F, Harendza T, Hubrich S, Lorenz A, Herzog C, Mueller M, et al. Syndecan-4 signalling inhibits apoptosis and controls NFAT activity during myocardial damage and remodelling. Cardiovasc Res. 2011;92:123-31 pubmed publisher
    ..The expression of syndecan-4 (Sdc4), a transmembrane proteoglycan, is up-regulated after MI, but its function in the heart remains unknown...
  4. Gao Y, Li M, Chen W, Simons M. Synectin, syndecan-4 cytoplasmic domain binding PDZ protein, inhibits cell migration. J Cell Physiol. 2000;184:373-9 pubmed
    ..We conclude that synectin is involved in syndecan-4-dependent interactions and may play a role in the assembly of syndecan-4 signaling complex. ..
  5. Bass M, Williamson R, Nunan R, Humphries J, Byron A, Morgan M, et al. A syndecan-4 hair trigger initiates wound healing through caveolin- and RhoG-regulated integrin endocytosis. Dev Cell. 2011;21:681-93 pubmed publisher
    ..Thus, this syndecan-4-regulated integrin endocytic pathway appears to play a key role in tissue repair. ..
  6. Bellin R, Kubicek J, Frigault M, Kamien A, Steward R, Barnes H, et al. Defining the role of syndecan-4 in mechanotransduction using surface-modification approaches. Proc Natl Acad Sci U S A. 2009;106:22102-7 pubmed publisher
    ..We believe that these results will be of interest to a wide range of fields, including mechanotransduction, syndecan biology, and cell-material interactions. ..
  7. Bass M, Morgan M, Roach K, Settleman J, Goryachev A, Humphries M. p190RhoGAP is the convergence point of adhesion signals from alpha 5 beta 1 integrin and syndecan-4. J Cell Biol. 2008;181:1013-26 pubmed publisher
    ..This molecular mechanism explains the cooperation between extracellular matrix receptors during cell adhesion. ..
  8. Deepa S, Yamada S, Zako M, Goldberger O, Sugahara K. Chondroitin sulfate chains on syndecan-1 and syndecan-4 from normal murine mammary gland epithelial cells are structurally and functionally distinct and cooperate with heparan sulfate chains to bind growth factors. A novel function to control binding. J Biol Chem. 2004;279:37368-76 pubmed
  9. Cornelison D, Wilcox Adelman S, Goetinck P, Rauvala H, Rapraeger A, Olwin B. Essential and separable roles for Syndecan-3 and Syndecan-4 in skeletal muscle development and regeneration. Genes Dev. 2004;18:2231-6 pubmed
    ..Further, syndecan-4(-/-) satellite cells fail to reconstitute damaged muscle, suggesting a unique requirement for syndecan-4 in satellite cell function. ..
  10. Midwood K, Valenick L, Hsia H, Schwarzbauer J. Coregulation of fibronectin signaling and matrix contraction by tenascin-C and syndecan-4. Mol Biol Cell. 2004;15:5670-7 pubmed
    ..In this way, tenascin-C and syndecan-4 work together to control fibroblast morphology and signaling and regulate events such as matrix contraction that are essential for efficient tissue repair. ..
  11. Bass M, Roach K, Morgan M, Mostafavi Pour Z, Schoen T, Muramatsu T, et al. Syndecan-4-dependent Rac1 regulation determines directional migration in response to the extracellular matrix. J Cell Biol. 2007;177:527-38 pubmed
  12. Kojima T, Shworak N, Rosenberg R. Molecular cloning and expression of two distinct cDNA-encoding heparan sulfate proteoglycan core proteins from a rat endothelial cell line. J Biol Chem. 1992;267:4870-7 pubmed
    ..HSPGinact core proteins demonstrate that the 30-kDa component is a previously unidentified species, designated as ryudocan, with the 25-kDa component representing a proteolytic degradation product, while the 50-kDa component is the rat ..
  13. Matsui Y, Ikesue M, Danzaki K, Morimoto J, Sato M, Tanaka S, et al. Syndecan-4 prevents cardiac rupture and dysfunction after myocardial infarction. Circ Res. 2011;108:1328-39 pubmed publisher
    ..These results suggest that Syn4 plays an important role in the inflammatory response and granulation tissue formation, thereby preventing cardiac rupture and dysfunction after MI. ..
  14. Gopal S, Multhaupt H, Pocock R, Couchman J. Cell-extracellular matrix and cell-cell adhesion are linked by syndecan-4. Matrix Biol. 2017;60-61:57-69 pubmed publisher
    ..This corresponds to the reduced ability of fibroblasts lacking syndecan-4 to exert tension on the ECM and we now show that this may extend to reduced tension in cell-cell adhesion. ..
  15. Lee S, Huynh T, Lee Y, Sebald S, Wilcox Adelman S, Iwamori N, et al. Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway. Proc Natl Acad Sci U S A. 2012;109:E2353-60 pubmed publisher
  16. Li R, Wu H, Xie J, Li G, Gu R, Kang L, et al. Syndecan-4 regulates the bFGF-induced chemotactic migration of endothelial cells. J Mol Histol. 2016;47:503-9 pubmed publisher
    ..b>Synd4 is a ubiquitous heparin sulfate proteoglycan receptor on the cell surface that has been identified to promote ..
  17. Lin T, Lu K, Chen W, Cheng C, Lin Y. Roles of syndecan-4 and relative kinases in dorsal root ganglion neuron adhesion and mechanotransduction. Neurosci Lett. 2015;592:88-93 pubmed publisher
    ..These results indicate that SDC4-pPKCα-FAKpTyr397-pERK1/2 may play a crucial role in DRG adhesion and mechanotransduction.
  18. Denhez F, Wilcox Adelman S, Baciu P, Saoncella S, Lee S, French B, et al. Syndesmos, a syndecan-4 cytoplasmic domain interactor, binds to the focal adhesion adaptor proteins paxillin and Hic-5. J Biol Chem. 2002;277:12270-4 pubmed
  19. Zhang Y, Li J, Partovian C, Sellke F, Simons M. Syndecan-4 modulates basic fibroblast growth factor 2 signaling in vivo. Am J Physiol Heart Circ Physiol. 2003;284:H2078-82 pubmed
    ..In conclusion, enhanced syndecan-4 expression in mouse cardiac endothelial cells results in preferential augmentation of FGF2 but not VEGF-A(165)-induced NO release. ..
  20. Mahoney C, Morgan M, Harrison A, Humphries M, Bass M. Therapeutic ultrasound bypasses canonical syndecan-4 signaling to activate rac1. J Biol Chem. 2009;284:8898-909 pubmed publisher
    ..By substituting for one of the key axes of adhesion-dependent signaling, ultrasound therapy has considerable potential as a clinical technique. ..
  21. Cui X, Li X, Shen X, Bae Y, Kang J, Kim N. Transcription profile in mouse four-cell, morula, and blastocyst: Genes implicated in compaction and blastocoel formation. Mol Reprod Dev. 2007;74:133-43 pubmed
    ..The identification of the genes being expressed in here will provide insight into the complex gene regulatory networks effecting compaction and blastocoel formation...
  22. Ikesue M, Matsui Y, Ohta D, Danzaki K, Ito K, Kanayama M, et al. Syndecan-4 deficiency limits neointimal formation after vascular injury by regulating vascular smooth muscle cell proliferation and vascular progenitor cell mobilization. Arterioscler Thromb Vasc Biol. 2011;31:1066-74 pubmed publisher
    ..Syn4 deficiency limits neointimal formation after vascular injury by regulating VSMC proliferation and VPC mobilization. Therefore, Syn4 may be a novel therapeutic target for preventing arterial restenosis after angioplasty. ..
  23. Suzuki N, Ichikawa N, Kasai S, Yamada M, Nishi N, Morioka H, et al. Syndecan binding sites in the laminin alpha1 chain G domain. Biochemistry. 2003;42:12625-33 pubmed
    ..These sites may play a critical role in the diverse biological activities involving heparin and syndecan-4 binding. ..
  24. Scarpellini A, Germack R, Lortat Jacob H, Muramatsu T, Billett E, Johnson T, et al. Heparan sulfate proteoglycans are receptors for the cell-surface trafficking and biological activity of transglutaminase-2. J Biol Chem. 2009;284:18411-23 pubmed publisher
    ..We propose that the membrane trafficking of TG2, and hence its extracellular activity, is linked to TG2 binding to cell-surface HSPG. ..
  25. Herum K, Lunde I, Skrbic B, Florholmen G, Behmen D, Sjaastad I, et al. Syndecan-4 signaling via NFAT regulates extracellular matrix production and cardiac myofibroblast differentiation in response to mechanical stress. J Mol Cell Cardiol. 2013;54:73-81 pubmed publisher
    ..This article is part of a Special Issue entitled 'Possible Editorial'. ..
  26. Endo T, Ito K, Morimoto J, Kanayama M, Ota D, Ikesue M, et al. Syndecan 4 Regulation of the Development of Autoimmune Arthritis in Mice by Modulating B Cell Migration and Germinal Center Formation. Arthritis Rheumatol. 2015;67:2512-22 pubmed publisher
    b>Syndecan 4 has been implicated as a critical mediator of inflammatory responses because of its functions as a coreceptor and reservoir for growth factors and chemokines...
  27. Lin W, Zhang J, Lin H, Li Z, Sun X, Xin D, et al. Syndecan-4 negatively regulates antiviral signalling by mediating RIG-I deubiquitination via CYLD. Nat Commun. 2016;7:11848 pubmed publisher
    ..Here we show that syndecan-4 (SDC4) is a RIG-I-interacting partner identified in a yeast two-hybrid screen...
  28. Escobedo N, Contreras O, Muñoz R, Farías M, Carrasco H, Hill C, et al. Syndecan 4 interacts genetically with Vangl2 to regulate neural tube closure and planar cell polarity. Development. 2013;140:3008-17 pubmed publisher
    b>Syndecan 4 (Sdc4) is a cell-surface heparan sulfate proteoglycan (HSPG) that regulates gastrulation, neural tube closure and directed neural crest migration in Xenopus development...
  29. Williamson R, Cowell C, Hammond C, Bergen D, Roper J, Feng Y, et al. Coronin-1C and RCC2 guide mesenchymal migration by trafficking Rac1 and controlling GEF exposure. J Cell Sci. 2014;127:4292-307 pubmed publisher
  30. Oritani K, Kincade P. Identification of stromal cell products that interact with pre-B cells. J Cell Biol. 1996;134:771-82 pubmed
    ..This approach resulted in the cloning of biglycan, syndecan 4, collagen type I, clusterin, matrix glycoprotein sc1, osteonectin, and one unknown molecule (designated SIM)...
  31. Ishiguro K, Kadomatsu K, Kojima T, Muramatsu H, Nakamura E, Ito M, et al. Syndecan-4 deficiency impairs the fetal vessels in the placental labyrinth. Dev Dyn. 2000;219:539-44 pubmed
    ..gestational days, the area of degenerated fetal vessels in the placental labyrinth was more diffuse and larger in Synd4(-/-) embryos than wild-type controls...
  32. Gopal S, Søgaard P, Multhaupt H, Pataki C, Okina E, Xian X, et al. Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels. J Cell Biol. 2015;210:1199-211 pubmed publisher
    ..The widespread and conserved syndecan-TRPC axis therefore fine tunes cytoskeletal organization and cell behavior. ..
  33. Li R, Xie J, Wu H, Li G, Chen J, Chen Q, et al. Syndecan-4 shedding impairs macrovascular angiogenesis in diabetes mellitus. Biochem Biophys Res Commun. 2016;474:15-21 pubmed publisher
    Syndecan-4 (synd4) is a ubiquitous heparan sulfate proteoglycan cell surface receptor that modulates cell proliferation, migration, mechanotransduction, and endocytosis...
  34. Wang Z, Collighan R, Gross S, Danen E, Orend G, Telci D, et al. RGD-independent cell adhesion via a tissue transglutaminase-fibronectin matrix promotes fibronectin fibril deposition and requires syndecan-4/2 ?5?1 integrin co-signaling. J Biol Chem. 2010;285:40212-29 pubmed publisher
  35. Zimmermann N, Saiga H, Houthuys E, Moura Alves P, Koehler A, Bandermann S, et al. Syndecans promote mycobacterial internalization by lung epithelial cells. Cell Microbiol. 2016;18:1846-1856 pubmed publisher
    ..We identified syndecan 4 (Sdc4) as mycobacterial attachment receptor on alveolar epithelial cells...
  36. Yoo J, Jeong M, Cho H, Oh E, Han M. Dynamin II interacts with syndecan-4, a regulator of focal adhesion and stress-fiber formation. Biochem Biophys Res Commun. 2005;328:424-31 pubmed
    ..All of these results suggest that the interaction between dynamin II and syndecan-4 is important in mediating focal adhesion and stress-fiber formation. ..
  37. Ju R, Zhuang Z, Zhang J, Lanahan A, Kyriakides T, Sessa W, et al. Angiopoietin-2 secretion by endothelial cell exosomes: regulation by the phosphatidylinositol 3-kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) and syndecan-4/syntenin pathways. J Biol Chem. 2014;289:510-9 pubmed publisher
    ..This novel mechanism connects three critical signaling pathways: angiopoietin/Tie2, PI3K/Akt/eNOS, and syndecan/syntenin, which play important roles in vascular growth and stabilization. ..
  38. Kim E, Roshanravan H, Dryer S. Syndecan-4 ectodomain evokes mobilization of podocyte TRPC6 channels and their associated pathways: An essential role for integrin signaling. Biochim Biophys Acta. 2015;1853:2610-20 pubmed publisher
    PodocyteTRPC6 channels have been implicated in glomerular diseases. Syndecan-4 (Sdc4) is a membrane proteoglycan that can be cleaved to release a soluble ectodomain capable of paracrine and autocrine signaling...
  39. Das S, Monteforte A, Singh G, Majid M, Sherman M, Dunn A, et al. Syndecan-4 Enhances Therapeutic Angiogenesis after Hind Limb Ischemia in Mice with Type 2 Diabetes. Adv Healthc Mater. 2016;5:1008-13 pubmed publisher
    ..Syndecan-4 therapy also induces a marked immunomodulation in the tissues, increasing the polarization of macrophages toward the M2 phenotype. ..
  40. Chung J, Tomihari M, Tamura K, Kojima T, Cruz P, Ariizumi K. The DC-HIL ligand syndecan-4 is a negative regulator of T-cell allo-reactivity responsible for graft-versus-host disease. Immunology. 2013;138:173-82 pubmed publisher
    ..We conclude that SD-4, as the T-cell ligand of DC-HIL, is a potent inhibitor of allo-reactive T cells responsible for GVHD and a potentially useful target for treating this disease. ..
  41. Patterson A, Delday M, van Kuppevelt T, Loh G, Blaut M, Haller D, et al. Expression of heparan sulfate proteoglycans in murine models of experimental colitis. Inflamm Bowel Dis. 2012;18:1112-26 pubmed publisher
    ..The IL10(-/-) mouse is a useful model for further study of the functional role of HSPGs in chronic inflammation and in maintaining healthy gut barrier. ..
  42. Zako M, Dong J, Goldberger O, Bernfield M, Gallagher J, Deakin J. Syndecan-1 and -4 synthesized simultaneously by mouse mammary gland epithelial cells bear heparan sulfate chains that are apparently structurally indistinguishable. J Biol Chem. 2003;278:13561-9 pubmed
  43. Hikake T, Mori T, Iseki K, Hagino S, Zhang Y, Takagi H, et al. Comparison of expression patterns between CREB family transcription factor OASIS and proteoglycan core protein genes during murine tooth development. Anat Embryol (Berl). 2003;206:373-80 pubmed
    ..These results suggest that the OASIS gene might be related to proteoglycan expression and may play an important role in the differentiation of the odontoblast and cells in inner enamel epithelium. ..
  44. Chung J, Dougherty I, Cruz P, Ariizumi K. Syndecan-4 mediates the coinhibitory function of DC-HIL on T cell activation. J Immunol. 2007;179:5778-84 pubmed
    ..We conclude that SD-4 is the T cell ligand through which DC-HIL mediates its negative coregulatory function. ..
  45. Cevikbas F, Schaefer L, Uhlig P, Robenek H, Theilmeier G, Echtermeyer F, et al. Unilateral nephrectomy leads to up-regulation of syndecan-2- and TGF-beta-mediated glomerulosclerosis in syndecan-4 deficient male mice. Matrix Biol. 2008;27:42-52 pubmed
    ..By contrast, signaling through syndecan-4 negatively controls the production of pro-sclerotic TGF-beta1. ..
  46. Bertrand J, Stange R, Hidding H, Echtermeyer F, Nalesso G, Godmann L, et al. Syndecan 4 supports bone fracture repair, but not fetal skeletal development, in mice. Arthritis Rheum. 2013;65:743-52 pubmed publisher
    b>Syndecan 4, a heparan sulfate proteoglycan, has been associated with osteoarthritis...
  47. Chung J, Cruz P, Ariizumi K. Inhibition of T-cell activation by syndecan-4 is mediated by CD148 through protein tyrosine phosphatase activity. Eur J Immunol. 2011;41:1794-9 pubmed publisher
    ..These findings indicate that SD-4 is unique among known T-cell coinhibitors, in employing CD148 to inhibit T-cell activation at a site distal from the synapse. ..
  48. Ishiguro K, Kojima T, Muramatsu T. Syndecan-4 as a molecule involved in defense mechanisms. Glycoconj J. 2002;19:315-8 pubmed
    Syndecan-4 is a transmembrane heparan sulfate proteoglycan belonging to the syndecan family. Syndecan-4-deficient [(Synd4(-/-)] mice were produced to clarify the in vivo role of syndecan-4...
  49. Telci D, Wang Z, Li X, Verderio E, Humphries M, Baccarini M, et al. Fibronectin-tissue transglutaminase matrix rescues RGD-impaired cell adhesion through syndecan-4 and beta1 integrin co-signaling. J Biol Chem. 2008;283:20937-47 pubmed publisher
  50. San Martin S, Soto Suazo M, Zorn T. Perlecan and syndecan-4 in uterine tissues during the early pregnancy in mice. Am J Reprod Immunol. 2004;52:53-9 pubmed
    ..The coordinate balance between the pre- and post-implantation periods suggests a role of these two molecules in the adaptive modification of the uterine microenvironment to receive and implant the embryo. ..
  51. Vihinen T, Maatta A, Jaakkola P, Auvinen P, Jalkanen M. Functional characterization of mouse syndecan-1 promoter. J Biol Chem. 1996;271:12532-41 pubmed
    ..We assume that the constitutive high level gene expression in epithelial cells is achieved by the proximal promoter, which is controlled by members of Sp1 transcription factor family. ..
  52. Tanino Y, Chang M, Wang X, Gill S, Skerrett S, McGuire J, et al. Syndecan-4 regulates early neutrophil migration and pulmonary inflammation in response to lipopolysaccharide. Am J Respir Cell Mol Biol. 2012;47:196-202 pubmed publisher
    ..These findings indicate that the early inflammatory response to LPS involves marked up-regulation of syndecan-4, which functions to limit the extent of pulmonary inflammation and lung injury. ..
  53. Herum K, Lunde I, Skrbic B, Louch W, Hasic A, Boye S, et al. Syndecan-4 is a key determinant of collagen cross-linking and passive myocardial stiffness in the pressure-overloaded heart. Cardiovasc Res. 2015;106:217-26 pubmed publisher