Syndecan interactions (Homo sapiens)

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4, 5, 971, 13, 146, 122113cytosolTHBS1 HS(6)-SDC1 Syndecan-1:Fibronectin matrixSyndecan-1, 2 &4:VTNSyndecan-1 PI(4,5)P2HS(6)-SDC2 HS(1)-SDC4 Syndecan-4:ACTN1HS(4)-SDC4 HS(4)-SDC1 HS(5)-SDC1 HS(1)-SDC2 TRAPPC4 Collagen type I fibril ITGB4 HS(6)-SDC1 HS(2)-SDC4 Integrin alphaVbeta5HS(4)-SDC1 Syndecan-1:Integrinalpha2beta1(alpha6beta4)Integrinalpha2beta1,(alpha6beta4)HS(2)-SDC1 HS(6)-SDC4 ITGA2 HS(1)-SDC1 Syndecan-4 Syndecan-1:IntegrinalphaVbeta5THBS1PRKCA HS(1)-SDC4 Syndecan-4:PI(4,5)P2ITGAV(31-1048) DAG DAG HS(6)-SDC4 HS(2)-SDC3 HS(1)-SDC1 VTNHS(3)-SDC4 HS(4)-SDC3 HS(1)-SDC1 HS(5)-SDC2 HS(2)-SDC2 Syndecan-2 HS(6)-SDC1 TNC HS(6)-SDC1 HS(2)-SDC1 Syndecan-1:Collagentypes I, III, VSyndecan-2:CASKSyndecan-2 HS(1)-SDC1 Syndecan-1HS(5)-SDC1 TNC:Syndecan-3HS(4)-SDC3 HS(4)-SDC1 Syndecans 1, 2 & 4Fibronectin matrix HS(6)-SDC3 SDC1,2,4,(3):FGF2HS(3)-SDC3 Syndecan-4ACTN1ITGB3 HS(4)-SDC1 ITGAV(31-1048) Collagen type I fibril Syndecan-2HS(5)-SDC3 HS(5)-SDC2 HS(5)-SDC4 Syndecan-4 TGFB1 Syndecan-4 PRKCA HS(3)-SDC1 Syndecan-2 Collagen type V fibril ITGB3 HS(4)-SDC4 Syndecans 2, (4)HS(3)-SDC2 ITGAV(31-1048) HS(3)-SDC4 HS(5)-SDC3 HS(2)-SDC4 HS(4)-SDC4 HS(3)-SDC1 HS(5)-SDC1 HS(5)-SDC2 Syndecan-4 CASKHS(6)-SDC1 Fibronectin matrixSyndecan-4 HS(4)-SDC4 HS(3)-SDC1 HS(1)-SDC1 ITGB4 HS(1)-SDC1 HS(5)-SDC1 Collagen type III fibril Collagen type V fibril HS(4)-SDC1 HS(2)-SDC1 ITGB1 ITGAV(31-1048) ITGB3 HS(1)-SDC1 HS(3)-SDC1 Syndecan-3 HS(6)-SDC1 HS(2)-SDC4 HS(1)-SDC4 ITGB3 Syndecan-3VTN Syndecan-1:IntegrinalphaVbeta3SDC1, 2, 4, (3)HS(3)-SDC3 ITGB5 ACTN1 HS(4)-SDC1 Collagen types I,III, VITGB5 HS(2)-SDC2 HS(4)-SDC2 Syndecan-1:THBS1ITGAV(31-1048) HS(1)-SDC4 HS(3)-SDC1 PI(4,5)P2 HS(3)-SDC1 HS(2)-SDC1 Integrin alphaVbeta3HS(6)-SDC4 ITGB5 HS(2)-SDC2 Protein Kinase C,alpha type: DAGHS(3)-SDC4 HS(3)-SDC2 ITGB5 Syndecan-1 ITGAV(31-1048) Syndecan-1 ITGA2 HS(5)-SDC1 HS(4)-SDC2 Syndecan-2 Syndecans 2,(4):TGFB1ITGA6(24-1130) HS(5)-SDC4 HS(3)-SDC4 HS(2)-SDC1 HS(2)-SDC1 HS(2)-SDC4 Syndecan-2 HS(4)-SDC1 Collagen type III fibril FGF2(10-155) HS(6)-SDC1 HS(1)-SDC3 HS(6)-SDC2 Syndecan-4 HS(3)-SDC1 FGF2(10-155)HS(1)-SDC2 PI(4,5)P2 HS(6)-SDC3 HS(5)-SDC4 TNCHS(2)-SDC3 HS(5)-SDC4 HS(6)-SDC4 HS(6)-SDC2 HS(1)-SDC2 HS(5)-SDC1 TGFB1HS(4)-SDC2 Syndecan-1 HS(1)-SDC3 HS(2)-SDC1 Syndecan-3 HS(3)-SDC2 HS(5)-SDC1 Syndecan-2 CASK TRAPPC4ITGA6(24-1130) Syndecan-2:TRAPPC4Syndecan-4:PI(4,5)P2:Protein kinase C, alpha type:DAGITGB1 10810


Description

Syndecans are type I transmembrane proteins, with an N-terminal ectodomain that contains several consensus sequences for glycosaminoglycan (GAG) attachment and a short C-terminal cytoplasmic domain. Syndecan-1 and -3 GAG attachment sites occur in two distinct clusters, one near the N-terminus and the other near the membrane-attachment site, separated by a proline and threonine-rich 'spacer'. Syndecan ectodomain sequences are poorly conserved in the family and between species, but the transmembrane and cytoplasmic domains are highly conserved. Syndecan-1 and -3 form a subfamily. Syndecan core proteins form dimers (Choi et al. 2007) and at least syndecan-3 and -4 form oligomers (Asundi & Carey 1995, Shin et al. 2012). Syndecan-1 is the major syndecan of epithelial cells including vascular endothelium. Syndecan-2 is present mostly in mesenchymal, neuronal and smooth muscle cells. Syndecan-3 is the major syndecan of the nervous system, while syndecan-4 is ubiquitously expressed but at lower levels than the other syndecans (refs in Alexopoulou et al. 2007). The core syndecan protein has three to five heparan sulfate or chondroitin sulfate chains, which interact with a variety of ligands including fibroblast growth factors, vascular endothelial growth factor, transforming growth factor-beta, fibronectin, collagen, vitronectin and several integrins. Syndecans may act as integrin coreceptors. Interactions between fibronectin and syndecans are modulated by tenascin-C.

Syndecans bind a wide variety of soluble and insoluble ligands, inckluding extracellular matrix components, cell adhesion molecules, growth factors, cytokines, and proteinases. As the cleaved ectodomains of syndecans retain the ability to bind ligands, ectodomain shedding is a mechanism for releasing soluble effectors that may compete for ligands with their cell-bound counterparts (Kainulainen et al. 1998). Shed ectodomains are found in inflammatory fluids (Subramanian et al. 1997) and may induce the proliferation of cancer cells (Maeda et al. 2004).

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Reactome-Converter 
Pathway is converted from Reactome ID: 3000170
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Reactome version: 66
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Reactome Author: Jupe, Steve

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Bibliography

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  1. Hozumi K, Suzuki N, Nielsen PK, Nomizu M, Yamada Y.; ''Laminin alpha1 chain LG4 module promotes cell attachment through syndecans and cell spreading through integrin alpha2beta1.''; PubMed Europe PMC
  2. Oh ES, Woods A, Couchman JR.; ''Multimerization of the cytoplasmic domain of syndecan-4 is required for its ability to activate protein kinase C.''; PubMed Europe PMC
  3. Saunders S, Bernfield M.; ''Cell surface proteoglycan binds mouse mammary epithelial cells to fibronectin and behaves as a receptor for interstitial matrix.''; PubMed Europe PMC
  4. Alexopoulou AN, Multhaupt HA, Couchman JR.; ''Syndecans in wound healing, inflammation and vascular biology.''; PubMed Europe PMC
  5. Couchman JR.; ''Transmembrane signaling proteoglycans.''; PubMed Europe PMC
  6. Ishiguro K, Kojima T, Muramatsu T.; ''Syndecan-4 as a molecule involved in defense mechanisms.''; PubMed Europe PMC
  7. Wilkins-Port CE, Sanderson RD, Tominna-Sebald E, McKeown-Longo PJ.; ''Vitronectin's basic domain is a syndecan ligand which functions in trans to regulate vitronectin turnover.''; PubMed Europe PMC
  8. Tanimura A, Nezu A, Morita T, Hashimoto N, Tojyo Y.; ''Interplay between calcium, diacylglycerol, and phosphorylation in the spatial and temporal regulation of PKCalpha-GFP.''; PubMed Europe PMC
  9. Tkachenko E, Rhodes JM, Simons M.; ''Syndecans: new kids on the signaling block.''; PubMed Europe PMC
  10. Ross D, Joyner WL.; ''Resting distribution and stimulated translocation of protein kinase C isoforms alpha, epsilon and zeta in response to bradykinin and TNF in human endothelial cells.''; PubMed Europe PMC
  11. Steinfeld R, Van Den Berghe H, David G.; ''Stimulation of fibroblast growth factor receptor-1 occupancy and signaling by cell surface-associated syndecans and glypican.''; PubMed Europe PMC
  12. Chen L, Klass C, Woods A.; ''Syndecan-2 regulates transforming growth factor-beta signaling.''; PubMed Europe PMC
  13. Ogawa T, Tsubota Y, Hashimoto J, Kariya Y, Miyazaki K.; ''The short arm of laminin gamma2 chain of laminin-5 (laminin-332) binds syndecan-1 and regulates cellular adhesion and migration by suppressing phosphorylation of integrin beta4 chain.''; PubMed Europe PMC
  14. Beauvais DM, Burbach BJ, Rapraeger AC.; ''The syndecan-1 ectodomain regulates alphavbeta3 integrin activity in human mammary carcinoma cells.''; PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
101431view11:30, 1 November 2018ReactomeTeamreactome version 66
100969view21:08, 31 October 2018ReactomeTeamreactome version 65
100506view19:42, 31 October 2018ReactomeTeamreactome version 64
100052view16:25, 31 October 2018ReactomeTeamreactome version 63
99604view14:59, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99218view12:44, 31 October 2018ReactomeTeamreactome version 62
93975view13:49, 16 August 2017ReactomeTeamreactome version 61
93576view11:27, 9 August 2017ReactomeTeamreactome version 61
88415view11:52, 5 August 2016FehrhartOntology Term : 'syndecan signaling pathway' added !
86680view09:24, 11 July 2016ReactomeTeamreactome version 56
83417view11:10, 18 November 2015ReactomeTeamVersion54
81618view13:09, 21 August 2015ReactomeTeamVersion53
77077view08:37, 17 July 2014ReactomeTeamFixed remaining interactions
76782view12:14, 16 July 2014ReactomeTeamFixed remaining interactions
76105view10:17, 11 June 2014ReactomeTeamRe-fixing comment source
75817view11:36, 10 June 2014ReactomeTeamReactome 48 Update
75167view14:11, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74814view08:54, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ACTN1 ProteinP12814 (Uniprot-TrEMBL)
ACTN1ProteinP12814 (Uniprot-TrEMBL)
CASK ProteinO14936 (Uniprot-TrEMBL)
CASKProteinO14936 (Uniprot-TrEMBL)
Collagen type I fibril R-HSA-1474201 (Reactome)
Collagen type III fibril R-HSA-1474212 (Reactome)
Collagen type V fibril R-HSA-1609685 (Reactome)
Collagen types I, III, VComplexR-HSA-2731136 (Reactome)
DAG MetaboliteCHEBI:17815 (ChEBI)
FGF2(10-155) ProteinP09038 (Uniprot-TrEMBL)
FGF2(10-155)ProteinP09038 (Uniprot-TrEMBL)
Fibronectin matrix R-HSA-2327729 (Reactome)
Fibronectin matrixR-HSA-2327729 (Reactome)
HS(1)-SDC1 ProteinP18827 (Uniprot-TrEMBL)
HS(1)-SDC2 ProteinP34741 (Uniprot-TrEMBL)
HS(1)-SDC3 ProteinO75056 (Uniprot-TrEMBL)
HS(1)-SDC4 ProteinP31431 (Uniprot-TrEMBL)
HS(2)-SDC1 ProteinP18827 (Uniprot-TrEMBL)
HS(2)-SDC2 ProteinP34741 (Uniprot-TrEMBL)
HS(2)-SDC3 ProteinO75056 (Uniprot-TrEMBL)
HS(2)-SDC4 ProteinP31431 (Uniprot-TrEMBL)
HS(3)-SDC1 ProteinP18827 (Uniprot-TrEMBL)
HS(3)-SDC2 ProteinP34741 (Uniprot-TrEMBL)
HS(3)-SDC3 ProteinO75056 (Uniprot-TrEMBL)
HS(3)-SDC4 ProteinP31431 (Uniprot-TrEMBL)
HS(4)-SDC1 ProteinP18827 (Uniprot-TrEMBL)
HS(4)-SDC2 ProteinP34741 (Uniprot-TrEMBL)
HS(4)-SDC3 ProteinO75056 (Uniprot-TrEMBL)
HS(4)-SDC4 ProteinP31431 (Uniprot-TrEMBL)
HS(5)-SDC1 ProteinP18827 (Uniprot-TrEMBL)
HS(5)-SDC2 ProteinP34741 (Uniprot-TrEMBL)
HS(5)-SDC3 ProteinO75056 (Uniprot-TrEMBL)
HS(5)-SDC4 ProteinP31431 (Uniprot-TrEMBL)
HS(6)-SDC1 ProteinP18827 (Uniprot-TrEMBL)
HS(6)-SDC2 ProteinP34741 (Uniprot-TrEMBL)
HS(6)-SDC3 ProteinO75056 (Uniprot-TrEMBL)
HS(6)-SDC4 ProteinP31431 (Uniprot-TrEMBL)
ITGA2 ProteinP17301 (Uniprot-TrEMBL)
ITGA6(24-1130) ProteinP23229 (Uniprot-TrEMBL)
ITGAV(31-1048) ProteinP06756 (Uniprot-TrEMBL)
ITGB1 ProteinP05556 (Uniprot-TrEMBL)
ITGB3 ProteinP05106 (Uniprot-TrEMBL)
ITGB4 ProteinP16144 (Uniprot-TrEMBL)
ITGB5 ProteinP18084 (Uniprot-TrEMBL)
Integrin

alpha2beta1,

(alpha6beta4)
ComplexR-HSA-2731104 (Reactome)
Integrin alphaVbeta3ComplexR-HSA-210216 (Reactome)
Integrin alphaVbeta5ComplexR-HSA-1299497 (Reactome)
PI(4,5)P2 MetaboliteCHEBI:18348 (ChEBI)
PI(4,5)P2MetaboliteCHEBI:18348 (ChEBI)
PRKCA ProteinP17252 (Uniprot-TrEMBL)
Protein Kinase C, alpha type: DAGComplexR-HSA-422275 (Reactome)
SDC1, 2, 4, (3)ComplexR-HSA-2684511 (Reactome)
SDC1,2,4,(3):FGF2ComplexR-HSA-2684512 (Reactome)
Syndecan-1 R-HSA-2684506 (Reactome)
Syndecan-1, 2 & 4:VTNComplexR-HSA-2731126 (Reactome)
Syndecan-1:Collagen types I, III, VComplexR-HSA-2731134 (Reactome)
Syndecan-1:Fibronectin matrixComplexR-HSA-2731114 (Reactome)
Syndecan-1:Integrin

alpha2beta1

(alpha6beta4)
ComplexR-HSA-2731084 (Reactome)
Syndecan-1:Integrin alphaVbeta3ComplexR-HSA-2731073 (Reactome)
Syndecan-1:Integrin alphaVbeta5ComplexR-HSA-2731079 (Reactome)
Syndecan-1:THBS1ComplexR-HSA-2731077 (Reactome)
Syndecan-1ComplexR-HSA-2684506 (Reactome)
Syndecan-2 R-HSA-2684508 (Reactome)
Syndecan-2:CASKComplexR-HSA-2750169 (Reactome)
Syndecan-2:TRAPPC4ComplexR-HSA-2750174 (Reactome)
Syndecan-2ComplexR-HSA-2684508 (Reactome)
Syndecan-3 R-HSA-2681673 (Reactome)
Syndecan-3ComplexR-HSA-2681673 (Reactome)
Syndecan-4 R-HSA-2684509 (Reactome)
Syndecan-4:ACTN1ComplexR-HSA-2750171 (Reactome)
Syndecan-4:PI(4,5)P2:Protein kinase C, alpha type:DAGComplexR-HSA-2750166 (Reactome)
Syndecan-4:PI(4,5)P2ComplexR-HSA-2731080 (Reactome)
Syndecan-4ComplexR-HSA-2684509 (Reactome)
Syndecans 1, 2 & 4ComplexR-HSA-2731095 (Reactome)
Syndecans 2, (4):TGFB1ComplexR-HSA-2731087 (Reactome)
Syndecans 2, (4)ComplexR-HSA-2731096 (Reactome)
TGFB1 ProteinP01137 (Uniprot-TrEMBL)
TGFB1ProteinP01137 (Uniprot-TrEMBL)
THBS1 ProteinP07996 (Uniprot-TrEMBL)
THBS1ProteinP07996 (Uniprot-TrEMBL)
TNC ProteinP24821 (Uniprot-TrEMBL)
TNC:Syndecan-3ComplexR-HSA-2682267 (Reactome)
TNCProteinP24821 (Uniprot-TrEMBL)
TRAPPC4 ProteinQ9Y296 (Uniprot-TrEMBL)
TRAPPC4ProteinQ9Y296 (Uniprot-TrEMBL)
VTN ProteinP04004 (Uniprot-TrEMBL)
VTNProteinP04004 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
ACTN1R-HSA-2731149 (Reactome)
CASKR-HSA-2750181 (Reactome)
Collagen types I, III, VR-HSA-2731075 (Reactome)
FGF2(10-155)R-HSA-2684507 (Reactome)
Fibronectin matrixR-HSA-2731141 (Reactome)
Integrin

alpha2beta1,

(alpha6beta4)
R-HSA-2731074 (Reactome)
Integrin alphaVbeta3R-HSA-2731123 (Reactome)
Integrin alphaVbeta5R-HSA-2731081 (Reactome)
PI(4,5)P2R-HSA-2731147 (Reactome)
Protein Kinase C, alpha type: DAGR-HSA-2750187 (Reactome)
R-HSA-2681675 (Reactome) Syndecans have attached heparan sulfate (HS) and to a lesser extent chondroitin sulfate (CS) chains. These allow interactions with a large number of proteins, including heparin-binding growth factors such as fibroblast growth factors (Kiefer et al. 1990, Bernfield & Hooper 1991, Steinfeld et al. 1996), vascular endothelial growth factors (VEGFs) and transforming growth factor-Beta (Chen et al. 2000, Ishiguro et al. 2002). Various enzymes involved in post-translational HS chain modifications produce unique binding motifs that selectively recognize different proteins (Tkachenko et al. 2005). HS chains facilitate interactions of syndecan-1 with extracellular matrix proteins, including thrombospondin-1 (Sun et al. 1989, Lebakken & Rapraeger 1996, Adams et al. 2001, Yoneda & Couchman 2003). Syndecan-null mice have subtle phenotypes when compared with mice deficient in HS chain synthesis or modification (Echtermeyer et al. 2001, Ishiquro et al. 2001, Götte et al. 2002). GPI-anchored glypicans and matrix HSPGs such as perlecan may compensate for the absence of syndecans.
R-HSA-2681694 (Reactome) Tenascins are a family of 4 oligomeric extracellular glycoproteins, tenascin (TN) C, R, X, and W. In rotary shadowing images TNC is seen as a symmetrical structure called a hexabrachion (Erickson & Iglesias 1984). This hexamer is formed from initial trimers (Kammerer et al. 1988). All members of the family are believed able to form trimers but only C, R and W have the extra cysteine required for form hexamers. All have amino-terminal heptad repeats, epidermal growth factor (EGF)-like repeats, fibronectin type III domain repeats, and a carboxyl-terminal fibrinogen-like globular domain (Hsia & Schwartzbauer 2005). TNC was the first of the family to be discovered and is the best characterised (Midwood et al. 2011). Its subunits vary greatly in size (between 190 and 330 kDa of the tenascin-C monomer) due to glycosylation and splicing isoforms (Joester & Faissner 1999). During embryonic development TNC is expressed in neural, skeletal, and vascular tissues. In adults it is detectable only in tendon and tissues undergoing remodeling processes such as wound repair and neovascularization, or in pathological processes such as inflammation and tumorigenesis. TNR forms dimers and trimers (Norenberg et al. 1992) and is expressed only in the developing and adult central nervous system. TNC and TNR-null mice (single and double knock-outs) have surprisingly normal gross phenotypes, but exhibit behavioural and wound healing abnormalities (Mackie & Tucker 1999, Montag-Sallaz & Montag 2003). TNX (termed tenascin-Y in chicken) is the largest member of the family and is widely expressed during development, but in adults is limited to musculoskeletal, cardiac, and dermal tissue. It can form trimers, though it lacks the amino-terminal cysteine residues involved in hexamer formation. It is clearly associated with a variant of a heritable connective tissue disorder known as Ehler-Danlos Syndrome, which is associated with fibrillar collagen defects (Burch et al. 1997, Mao et al. 2002). TNY is thought to be an avian orthologue of TNX (Chiquet-Ehrismann 2004). TNW, first identified in zebrafish (Weber et al. 1998), is the least well characterized member of the tenascin family. It forms trimers and is expressed in developing skeletal tissue, neural crest cells and kidney, a pattern that partially overlaps with TN-C.

TNC binds syndecan-3 (Salmivirta et al. 1991, Koyama et al. 1996) Syndecans are type I transmembrane proteins, with an N-terminal ectodomain that contains several consensus sequences for glycosaminoglycan attachment and a short C-terminal cytoplasmic domain. Syndecan-1 and -3 glycosaminoglycan attachment sites occur in two distinct clusters, one near the N-terminus and the other near the membrane-attachment site, separated by a proline and threonine-rich 'spacer'. Syndecan ectodomain sequences are poorly conserved in the family and between species, but the transmembrane and cytoplasmic domains are highly conserved. Syndecan-1 and -3 form a subfamily. Syndecan-3 on the cell surface is frequently oligomeric (Asundi & Carey 1995). Syndecans bind extracellular ligands via their attached heparan sulphate chains, playing roles in cell to matrix and cell to cell adhesion.
R-HSA-2684507 (Reactome) Syndecans have attached heparan sulfate (HS) and to a lesser extent chondroitin sulfate (CS) chains. These allow interactions with a large number of proteins, including heparin-binding growth factors such as fibroblast growth factors (FGFs), mediating interaction with FGF receptors (Kiefer et al. 1990, Bernfield & Hooper 1991, Steinfeld et al. 1996, Chua et al. 2004). Various enzymes involved in post-translational HS chain modifications produce unique binding motifs that selectively recognize different proteins (Tkachenko et al. 2005).
R-HSA-2731074 (Reactome) Syndecans have attached heparan sulfate (HS) and to a lesser extent chondroitin sulfate (CS) chains. These allow interactions with a large number of proteins. Various enzymes involved in post-translational HS chain modifications produce unique binding motifs that selectively recognize different proteins (Tkachenko et al. 2005). It is thought that syndecans often act in concert with other receptors. Alpha2beta1 and alpha6beta4 integrins cooperate with syndecan-1 (SDC1) during adhesion to laminins (laminin alpha-1 Hozumi et al. 2006, laminin gamma-2, Ogawa et al. 2007, Wang et al. 2010). Interaction betweey SDC1 and alpha2beta1 integrin regulates cell adhesion to collagen (Vuoriluoto et al. 2008). SDC1 associates directly with the alphaVBeta3 and alphaVBeta5 integrins via its extracellular domain (Beauvais et al. 2004, McQuade et al. 2006). This association is required for integrin activation in a variety of carcinomas and probably reflects a generic role for the syndecan family as signaling 'hubs' at ECM adhesion sites (Fig. 1, Rapraeger 2013). The relationship between syndecans and co-receptors is not well understood (Alexopoulou et al. 2007). Syndecan-null mice have subtle phenotypes when compared with mice deficient in HS chain synthesis or modification (Echtermeyer et al. 2001, Ishiquro et al. 2001, Götte et al. 2002). GPI-anchored glypicans and matrix HSPGs such as perlecan may compensate for the absence of syndecans.
R-HSA-2731075 (Reactome) Syndecans have attached heparan sulfate (HS) and to a lesser extent chondroitin sulfate (CS) chains. These allow interactions with a large number of proteins. Various enzymes involved in post-translational HS chain modifications produce unique binding motifs that selectively recognize different proteins (Tkachenko et al. 2005). HS chains facilitate interactions of syndecan-1 with extracellular matrix proteins, including several types of collagen (type I, III and V - Koda et al. 1985). It is thought that syndecans often act in concert with other receptors, e.g. alphavbeta3 and alphavbeta5 integrins cooperate with syndecan-1 during adhesion to vitronectin (Beauvais et al. 2004, McQuade et al. 2006) while alpha2beta1 and alpha6beta4 integrins cooperate with syndecans during adhesion to laminin (laminin alpha-1 Hozumi et al. 2006, laminin gamma-2, Ogawa et al. 2007). Similarly syndecan-1 appears to support integrin alpha2Beta1-mediated adhesion to collagen (human to cow collagen I - Vuoriluoto et al. 2008). This relationship between syndecans and co-receptors is not well understood (Alexopoulou et al. 2007). Syndecan-null mice have subtle phenotypes when compared with mice deficient in HS chain synthesis or modification (Echtermeyer et al. 2001, Ishiquro et al. 2001, Götte et al. 2002).
R-HSA-2731078 (Reactome) Syndecans have attached heparan sulfate (HS) and to a lesser extent chondroitin sulfate (CS) chains. These allow interactions with a large number of proteins, including transforming growth factor-Beta (Chen et al. 2000, Ishiguro et al. 2002). Various enzymes involved in post-translational HS chain modifications produce unique binding motifs that selectively recognize different proteins (Tkachenko et al. 2005). HS chains facilitate interactions of syndecan-1 with extracellular matrix proteins, including fibronectin (Saunders & Bemfield 1988, Woods et al. 2000), vitronectin, several types of collagen (type I, III and V Koda et al. 1985), and thrombospondin-1 (Sun et al. 1989, Yoneda & Couchman 2003). It is thought that syndecans often act in concert with other receptors, e.g. alphavbeta3 and alphavbeta5 integrins cooperate with syndecan-1 during adhesion to vitronectin (Beauvais et al. 2004, McQuade et al. 2006) while alpha2beta1 and alpha6beta4 integrins cooperate with syndecans during adhesion to laminin (laminin alpha-1 Hozumi et al. 2006, laminin gamma-2, Ogawa et al. 2007). The relationship between syndecans and co-receptors is not well understood (Alexopoulou et al. 2007). Syndecan-null mice have subtle phenotypes when compared with mice deficient in HS chain synthesis or modification (Echtermeyer et al. 2001, Ishiquro et al. 2001, Götte et al. 2002). GPI-anchored glypicans and matrix HSPGs such as perlecan may compensate for the absence of syndecans. Syndecans are also signalling molecules, interacting with cytoplasmic proteins. Most of the work done has involved syndecan-4 (Multhaupt et al. 2009). Zebrafish and murine syndecan-4 V regions bind the membrane lipid phosphatidylinositol 4,5 bisphosphate (PtdIns4,5P2) undergoing a shape change revealed by NMR spectroscopy (Whiteford et al. 2008). The resulting complex is able to bind protein kinase C alpha which is persistently activated in the absence of Ca2+ (Oh et al. 1997, Lee et al. 1998, Keum et al. 2004). Syndecan-2 binds the kinase Ca2+/calmodulin associated serine/threonine kinase (CASK), a membrane-associated guanylate kinase (MAGUK) associated with intercellular junctions (Hsueh et al. 1998). Trafficking protein particle complex subunit 4 (TRAPPC4) is a syndecan-2 interacting protein also known as synbindin. It appears to be involved with postsynaptic membrane trafficking (Ethell et al. 2000). Syndecan-2 expression promotes dendritic spine maturation in neurons, and requires the C2 domain (Ethell et al. 2000), suggesting that syndecan-2 and synbindin recruit intracellular vesicles to postsynaptic sites. More recently TRAPPC4 was shown to be a component of the Transport Protein Particle, involved in endoplasmic reticulum-to-Golgi transport (Fan et al. 2009). The V-region of syndecan-4 interacts with the actin-bundling protein alpha-actinin (Greene et al. 2003, Choi et al. 2008, Shin et al. 2012), a direct link to the cell cytoskeleton.
R-HSA-2731081 (Reactome) Syndecans are type I transmembrane proteins, with an N-terminal ectodomain that contains several consensus sequences for glycosaminoglycan (GAG) attachment and a short C-terminal cytoplasmic domain. Syndecan-1 and -3 GAG attachment sites occur in two distinct clusters, one near the N-terminus and the other near the membrane-attachment site, separated by a proline and threonine-rich 'spacer'. Syndecan ectodomain sequences are poorly conserved in the family and between species, but the transmembrane and cytoplasmic domains are highly conserved. Syndecan-1 and -3 form a subfamily. Syndecan core proteins form dimers (Choi et al. 2007) and at least syndecan-3 and -4 form oligomers (Asundi & Carey 1995, Shin et al. 2012). Syndecan-1 is the major syndecan of epithelial cells including vascular endothelium. Syndecan-2 is present mostly in mesenchymal, neuronal and smooth muscle cells. Syndecan-3 is the major syndecan of the nervous system, while syndecan-4 is ubiquitously expressed but at lower levels than the other syndecans (refs in Alexopoulou et al. 2007).

Syndecans have attached heparan sulfate (HS) and to a lesser extent chondroitin sulfate (CS) chains. These allow interactions with a large number of proteins. Various enzymes involved in post-translational HS chain modifications produce unique binding motifs that selectively recognize different proteins (Tkachenko et al. 2005). It is thought that syndecans often act in concert with other receptors, e.g. integrins alphavbeta3 and alphavbeta5 cooperate with syndecan-1 during adhesion to vitronectin (Beauvais et al. 2004, McQuade et al. 2006). The relationship between syndecans and co-receptors is not well understood (Alexopoulou et al. 2007). Syndecan-null mice have subtle phenotypes when compared with mice deficient in HS chain synthesis or modification (Echtermeyer et al. 2001, Ishiquro et al. 2001, Götte et al. 2002). GPI-anchored glypicans and matrix HSPGs such as perlecan may compensate for the absence of syndecans.
R-HSA-2731122 (Reactome) Syndecans have attached heparan sulfate (HS) and to a lesser extent chondroitin sulfate (CS) chains. These allow interactions with a large number of proteins, including vitronectin (VTN) (Wilkins-Port & McKeown-Longo 1996, Wilkins-Port et al. 2003). It is thought that syndecans often act in concert with other receptors, e.g. integrins alphavbeta3 and alphavbeta5 cooperate with syndecan-1 during adhesion to vitronectin (Beauvais et al. 2004, McQuade et al. 2006) while alpha2beta1 and alpha6beta4 integrins cooperate with syndecans during adhesion to laminin (laminin alpha-1 Hozumi et al. 2006, laminin gamma-2, Ogawa et al. 2007). This relationship between syndecans and co-receptors is not well understood (Alexopoulou et al. 2007). Syndecan-null mice have subtle phenotypes when compared with mice deficient in HS chain synthesis or modification (Echtermeyer et al. 2001, Ishiquro et al. 2001, Götte et al. 2002). GPI-anchored glypicans and matrix HSPGs such as perlecan may compensate for the absence of syndecans.
R-HSA-2731123 (Reactome) Syndecans have attached heparan sulfate (HS) and to a lesser extent chondroitin sulfate (CS) chains. These allow interactions with a large number of proteins. Various enzymes involved in post-translational HS chain modifications produce unique binding motifs that selectively recognize different proteins (Tkachenko et al. 2005). It is thought that syndecans often act in concert with other receptors, e.g. alphavbeta3 and alphavbeta5 integrins cooperate with syndecan-1 during adhesion to vitronectin (Beauvais et al. 2004, McQuade et al. 2006). The relationship between syndecans and co-receptors is not well understood (Alexopoulou et al. 2007). Syndecan-null mice have subtle phenotypes when compared with mice deficient in HS chain synthesis or modification (Echtermeyer et al. 2001, Ishiquro et al. 2001, Götte et al. 2002).
R-HSA-2731141 (Reactome) Syndecans have attached heparan sulfate (HS) and to a lesser extent chondroitin sulfate (CS) chains. These allow interactions with a large number of proteins. Various enzymes involved in post-translational HS chain modifications produce unique binding motifs that selectively recognize different proteins (Tkachenko et al. 2005). Syndecans binds with extracellular matrix proteins, including fibronectin (Human syndecan-1, Saunders & Bernfield 1988; rat syndecan-4 in Woods et al. 2000; rat syndecan-2 to bovine fibronectin in Klass & Woods 2000). Syndecan-1 functions to regulate integrin activity and fibronectin fibril assembly (Stepp et al. 2010).
R-HSA-2731147 (Reactome) Syndecans have attached heparan sulfate (HS) and to a lesser extent chondroitin sulfate (CS) chains. These allow interactions with a large number of proteins. Syndecans are also signalling molecules, interacting with cytoplasmic proteins. Most studies have involved syndecan-4 (Multhaupt et al. 2009). Zebrafish and murine syndecan-4 V regions bind the membrane lipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) undergoing a shape change revealed by NMR spectroscopy (Oh et al. 1998, Whiteford et al. 2008). The resulting complex is able to bind protein kinase C alpha which is persistently activated in the absence of Ca2+ (Oh et al. 1997, Lee et al. 1998, Keum et al. 2004).
R-HSA-2731149 (Reactome) Syndecans have attached heparan sulfate (HS) and to a lesser extent chondroitin sulfate (CS) chains. These allow interactions with a large number of proteins. Various enzymes involved in post-translational HS chain modifications produce unique binding motifs that selectively recognize different proteins (Tkachenko et al. 2005). Syndecan-null mice have subtle phenotypes when compared with mice deficient in HS chain synthesis or modification (Echtermeyer et al. 2001, Ishiquro et al. 2001, Götte et al. 2002). GPI-anchored glypicans and matrix HSPGs such as perlecan may compensate for the absence of syndecans. Syndecans are also signalling molecules, interacting with cytoplasmic proteins. Most of the work done has involved syndecan-4 (Multhaupt et al. 2009). The V-region of syndecan-4 interacts with the actin-bundling protein alpha-actinin (Greene et al. 2003, Choi et al. 2008, Shin et al. 2012), a direct link to the cell cytoskeleton.
R-HSA-2750177 (Reactome) Syndecans have attached heparan sulfate (HS) and to a lesser extent chondroitin sulfate (CS) chains. These allow interactions with a large number of proteins. Various enzymes involved in post-translational HS chain modifications produce unique binding motifs that selectively recognize different proteins (Tkachenko et al. 2005). Syndecan-null mice have subtle phenotypes when compared with mice deficient in HS chain synthesis or modification (Echtermeyer et al. 2001, Ishiquro et al. 2001, Götte et al. 2002). GPI-anchored glypicans and matrix HSPGs such as perlecan may compensate for the absence of syndecans.

Syndecans are also signalling molecules, interacting with cytoplasmic proteins. Syndecan-2 binds Trafficking protein particle complex subunit 4 (TRAPPC4), also known as synbindin. It appears to be involved with postsynaptic membrane trafficking (Ethell et al. 2000). Syndecan-2 expression promotes dendritic spine maturation in neurons, and requires the C2 domain (Ethell et al. 2000), suggesting that syndecan-2 and synbindin recruit intracellular vesicles to postsynaptic sites. More recently TRAPPC4 was shown to be a component of the Transport Protein Particle, involved in endoplasmic reticulum-to-Golgi transport (Fan et al. 2009).
R-HSA-2750181 (Reactome) Syndecans have attached heparan sulfate (HS) and to a lesser extent chondroitin sulfate (CS) chains. These allow interactions with a large number of proteins. Various enzymes involved in post-translational HS chain modifications produce unique binding motifs that selectively recognize different proteins (Tkachenko et al. 2005). Syndecan-null mice have subtle phenotypes when compared with mice deficient in HS chain synthesis or modification (Echtermeyer et al. 2001, Ishiquro et al. 2001, Götte et al. 2002). GPI-anchored glypicans and matrix HSPGs such as perlecan may compensate for the absence of syndecans.

Syndecans are also signalling molecules, interacting with cytoplasmic proteins. Syndecan-2 binds the kinase Ca2+/calmodulin associated serine/threonine kinase (CASK), a membrane-associated guanylate kinase (MAGUK) associated with intercellular junctions (Hsueh et al. 1998).
R-HSA-2750187 (Reactome) Syndecans have attached heparan sulfate (HS) and to a lesser extent chondroitin sulfate (CS) chains. These allow interactions with a large number of proteins. Various enzymes involved in post-translational HS chain modifications produce unique binding motifs that selectively recognize different proteins (Tkachenko et al. 2005).

Syndecans are also signalling molecules, interacting with cytoplasmic proteins. Most of the work done has involved syndecan-4 (Multhaupt et al. 2009). Zebrafish and murine syndecan-4 V regions bind the membrane lipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) undergoing a shape change revealed by NMR spectroscopy (Oh et al. 1998, Whiteford et al. 2008). The resulting complex is able to bind protein kinase C alpha which is persistently activated in the absence of Ca2+ (Oh et al. 1997, Lee et al. 1998, Keum et al. 2004).
SDC1, 2, 4, (3)R-HSA-2684507 (Reactome)
SDC1,2,4,(3):FGF2ArrowR-HSA-2684507 (Reactome)
Syndecan-1, 2 & 4:VTNArrowR-HSA-2731122 (Reactome)
Syndecan-1:Collagen types I, III, VArrowR-HSA-2731075 (Reactome)
Syndecan-1:Fibronectin matrixArrowR-HSA-2731141 (Reactome)
Syndecan-1:Integrin

alpha2beta1

(alpha6beta4)
ArrowR-HSA-2731074 (Reactome)
Syndecan-1:Integrin alphaVbeta3ArrowR-HSA-2731123 (Reactome)
Syndecan-1:Integrin alphaVbeta5ArrowR-HSA-2731081 (Reactome)
Syndecan-1:THBS1ArrowR-HSA-2681675 (Reactome)
Syndecan-1R-HSA-2681675 (Reactome)
Syndecan-1R-HSA-2731074 (Reactome)
Syndecan-1R-HSA-2731075 (Reactome)
Syndecan-1R-HSA-2731081 (Reactome)
Syndecan-1R-HSA-2731123 (Reactome)
Syndecan-1R-HSA-2731141 (Reactome)
Syndecan-2:CASKArrowR-HSA-2750181 (Reactome)
Syndecan-2:TRAPPC4ArrowR-HSA-2750177 (Reactome)
Syndecan-2R-HSA-2750177 (Reactome)
Syndecan-2R-HSA-2750181 (Reactome)
Syndecan-3R-HSA-2681694 (Reactome)
Syndecan-4:ACTN1ArrowR-HSA-2731149 (Reactome)
Syndecan-4:PI(4,5)P2:Protein kinase C, alpha type:DAGArrowR-HSA-2750187 (Reactome)
Syndecan-4:PI(4,5)P2ArrowR-HSA-2731147 (Reactome)
Syndecan-4:PI(4,5)P2R-HSA-2750187 (Reactome)
Syndecan-4R-HSA-2731147 (Reactome)
Syndecan-4R-HSA-2731149 (Reactome)
Syndecans 1, 2 & 4R-HSA-2731122 (Reactome)
Syndecans 2, (4):TGFB1ArrowR-HSA-2731078 (Reactome)
Syndecans 2, (4)R-HSA-2731078 (Reactome)
TGFB1R-HSA-2731078 (Reactome)
THBS1R-HSA-2681675 (Reactome)
TNC:Syndecan-3ArrowR-HSA-2681694 (Reactome)
TNCR-HSA-2681694 (Reactome)
TRAPPC4R-HSA-2750177 (Reactome)
VTNR-HSA-2731122 (Reactome)
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