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FLASH GENE
Symbol SDC4 contributors: mct/pgu - updated : 15-03-2016
HGNC name syndecan 4
HGNC id 10661
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a NXIP motif important for cell binding activity
  • an ectodomain that can support cell attachment
    • mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to murine Sdc4 (82.4pc)
    homolog to rattus Sdc4 (80.7pc)
    Homologene
    FAMILY
  • syndecan proteoglycan family
    • CATEGORY adhesion , receptor membrane
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,lysosome
    text
  • NUDT16L1 co-localized with SDC4 cytoplasmic domain in focal contacts, and interacts with various cell adhesion adaptor proteins to control cell signaling
    • basic FUNCTION
  • cell surface proteoglycan that bears heparan sulfate
  • involved in cell adhesion and motility
  • important component of focal adhesions that is involved in cytoskeletal reorganization
  • with SDC3,function as coreceptors for tyrosine kinases and in cell adhesion
  • contributes to endothelial tubulogenesis through interactions with THBS1
  • critical intrinsic regulator of inflammatory reactions by protecting against osteopontin-mediated acute hepatic injury by masking functional domains of SPP1
  • inhibitory role in CD4 T cells
  • functions as a receptor in intracellular signaling
  • GPNMB binds to SDC4 on activated T cells and inhibits allogeneic T-cell responses
  • promotes plasma membrane retention of PIP(2) by negatively regulating PLC-dependent PIP(2) degradation
  • regulating ADAMTS5 activation and artilage breakdown in osteoarthritis
  • SDC4 and RSPO3 are essential for two Wnt/PCP-driven processes-gastrulation movements and head cartilage morphogenesis
  • regulates early neutrophil migration and pulmonary inflammation in response to lipopolysaccharide
  • is a regulator of MAPK signaling
  • SDC4 independently regulates multiple small GTPases to promote fibroblast migration during wound healing
  • can participate in the Wnt/PCP pathway, unveiling its importance during neural tube closure in mammalian embryos
  • acts as a signal transducer, and affects the growth and differentiation of a number of tissues and organs
  • SDC4 participates likely in amelogenesis, and FGF10 may modulate dental epithelial cell behaviors through the regulation of SDC4 expression
  • can act as a co-receptor of growth factors and proteins of the extracellular matrix by increasing the affinity of adhesion molecules to their specific receptors
  • plays a important role in acquisition of anoikis resistance and that the conferral of anoikis resistance may suffice to transform endothelial cells
  • involved in establishment of the lamellar structure of the annulus fibrosus of the intervertebral disc
  • is a ubiquitous heparan sulfate proteoglycan cell surface receptor that modulates cell proliferation, migration, mechanotransduction, and endocytosis
  • SDC4 shedding from vascular endothelial cells played an important role in the diabetes-related impairment of angiogenesis shedding from vascular endothelial cells
  • SDC4 antagonizes the activation of DDX58 in a CYLD-mediated deubiquitination-dependent process, thereby balancing antiviral signalling to avoid deleterious effects on host cells
  • SDC4 controls flow-induced lymphatic endothelial cells (LECs)
    • polarization via regulation of VANGL2 expression
    CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with CDCP1, with GIPC1 PDZ domain and with NUDT16L1
  • binds CXCL12 and CXCR4
  • binding to GPNMB
  • TGM2 interacting with SDC4
  • RSPO3 binds syndecan 4 (SDC4) and that together they activate Wnt/PCP signaling
  • initiates MAPK signaling, whereas SDC4-dependent FGFR1 macropinocytosis modulates the kinetics of MAPK activation
  • SDC4 also regulates the phosphorylation of AKT1 at threonine308 (Thr308), the second phosphorylation site required for the full AKT1 activation
  • following cyclic stretch, NFATC4 was activated in cardiac fibroblasts in a SDC4- and calcineurin-dependent manner
  • SDC4 interacts genetically with VANGL2 to regulate neural tube closure and planar cell polarity
  • TGM2-SDC4 interaction through heparan sulphate side chains, and knockdown of SDC4 reduces cell surface TGM2 activity and apoptotic cell clearance
  • potential molecular function of NUDT16L1 in the regulation of cell signaling via binding to SDC4
  • locally generated SDC4 may play a role in regulating TRPC6 channels, and may contribute to glomerular pathology
  • role for SDC4 in mediating matrix degradation in both intervertebral discs and cartilage by controlling ADAMTS5 function and MMP3 expression
  • SDC4 interacts with both DDX58 and deubiquitinase CYLD via its C-terminal intracellular region, and likely promotes redistribution of DDX58 and CYLD in a perinuclear pattern post viral infection
    • cell & other
  • endothelial cell surface associated
    • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in an estrogen receptor-negative, highly proliferative breast carcinoma subtype
    tumoral     --over  
    in testicular germ cell tumours (TGCTs)
    Susceptibility
    Variant & Polymorphism
    Candidate gene lower expression in the uninvolved dermis of venous leg ulcer may predispose to venous leg ulcer
    Marker
  • is differentially expressed in seminomas and in testicular germ cell tumours and might be a useful marker
    • Therapy target
    SystemTypeDisorderPubmed
    immunologyinflammatory 
    potential novel therapeutic tool for treating inflammatory diseases
    immunologyautoimmunearticular
    inhibition of SDC4 will be of great value for the treatment of cartilage damage in osteoarthritis
    ANIMAL & CELL MODELS