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FLASH GENE
Symbol SDC4 contributors: mct/pgu - updated : 15-03-2016
HGNC name syndecan 4
HGNC id 10661
Location 20q13.12      Physical location : 43.953.930 - 43.977.064
Synonym name
  • amphiglycan
  • ryudocan core protein
  • syndecan 4 (amphiglycan, ryudocan)
  • syndecan proteoglycan 4
  • Synonym symbol(s) HSPG3, SYND4, RYUDOCAN, MGC22217
    DNA
    TYPE functioning gene
    STRUCTURE 23.14 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    KCNK15 20q12-q13 potassium channel, subfamily K, member 15 RIMS4 20 regulating synaptic membrane exocytosis 4 LOC391252 20 similar to piggyBac transposable element derived 4 YWHAB 20q13.1 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta polypeptide LOC200226 20q13.12 similar to Polyadenylate-binding protein 2 (Poly(A)-binding protein 2) (PABP 2) TOMM34 20q12-q13.11 translocase of outer mitochondrial membrane 34 STK4 20q11.2-q13.2 serine/threonine kinase 4 KCNS1 20q12 potassium voltage-gated channel, delayed-rectifier, subfamily S, member 1 WFDC5 20q13.11 WAP four-disulfide core domain 5 WFDC12 20q12-q13.1 WAP four-disulfide core domain 12 PI3 20q12-q13 protease inhibitor 3, skin-derived (SKALP) SEMG1 20q13.1 semenogelin I SEMG2 20q13.1 semenogelin II LOC149709 20q13.12 similar to RIKEN cDNA 1700049M11 SLPI 20q12-q13.2 secretory leukocyte protease inhibitor (antileukoproteinase) MATN4 20q13.1-q13.2 matrilin 4 RBPSUHL 20q12-q13.1 recombining binding protein suppressor of hairless (Drosophila)-like SDC4 20q13.1 syndecan 4 (amphiglycan, ryudocan) C20orf35 20q13.12 chromosome 20 open reading frame 35 C20orf10 20q12-13.12 chromosome 20 open reading frame 10 PIGT 20q12-q13.1 phosphatidyl inositol glycan class T LOC149710 20q13.12 hypothetical LOC149710 WFDC2 20q12-q13.2 WAP four-disulfide core domain 2 WFDC6 20q13.12 WAP four-disulfide core domain 6 SPINLW1 20q12-q13.2 serine protease inhibitor-like, with Kunitz and WAP domains 1 (eppin) WFDC8 20q13.12 WAP four-disulfide core domain 8 WFDC9 20q12-q13.1 WAP four-disulfide core domain 9 WFDC10A 20q13.12 WAP four-disulfide core domain 10A RPS2L1 20q13.11 ribosomal protein S2-like 1 WFDC11 20q12-q13.1 WAP four-disulfide core domain 11 WFDC10B 20 WAP four-disulfide core domain 10B WFDC13 20q13.12 WAP four-disulfide core domain 13 LOC391253 20 similar to dJ601O1.1 (novel protein with Kunitz/Bovine pancreatic trypsin inhibitor domain) HNRPA1P3 20q13.12 heterogeneous nuclear ribonucleoprotein A1 pseudogene 3 WFDC3 20q13.12 WAP four-disulfide core domain 3 DNTTIP1 20q13.12 deoxynucleotidyltransferase, terminal, interacting protein 1 UBE2C 20q12-q13.1 ubiquitin-conjugating enzyme E2C TNNC2 20q12-q13.11 troponin C2, fast C20orf161 20q13.11 chromosome 20 open reading frame 161
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 2640 - 198 - 2002 11805099
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveesophagus   highly
    Reproductivemale systemprostate   
    Respiratorylung   highly
     respiratory tracttrachea  highly
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/lining   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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