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FLASH GENE
Symbol THBS4 contributors: mct - updated : 21-03-2021
HGNC name thrombospondin 4
HGNC id 11788
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • polypeptide lacking the procollagen homology domain and type I repeats (TSP) of THBS1,with type II (EGF-like) and seven type III (Ca++ binding) repeats
  • (T3R) and TSP-C domains
  • a LamG domain for localization to the Golgi apparatus
  • conjugated GlycoP
    mono polymer homomer , trimer
    HOMOLOGY
    interspecies homolog to murine Thbs4
    Homologene
    FAMILY
  • thrombospondin family
  • extracellular calcium-binding protein family
  • CATEGORY adhesion
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • basement membrane
  • localized to the ER and post-ER vesicles
  • basic FUNCTION
  • mediating cell to cell and cell to matrix interactions
  • extracellular-matrix glycoproteins implicated in the control of synaptogenesis and neurite growth
  • glycoprotein involved in inflammatory responses and synaptogenesis
  • involved in cell adhesion and migration
  • important role for this matricellular protein in the local regulation of inflammation associated with atherogenesis
  • highly conserved matricellular protein regulating inflammation, angiogenesis and extracellular matrix remodeling
  • is involved in regulating the adaptive responses of the heart to pressure overload, suggesting its important role in myocardial remodeling
  • myocyte-interstitial mechano-signaling molecule central to adaptive cardiac contractile responses to acute stress, which appears to play a crucial role in the transition to chronic cardiac dilatation and failure
  • injury-induced spinal TSP4 may contribute to spinal presynaptic hypersensitivity and neuropathic pain states
  • THBS4 expression in breast cancer-associated extracellular matrix contributes to the activated stromal response exhibited during tumour progression and this may facilitate invasion of tumour cells
  • functions as an extracellular matrix (ECM) scaffold at myotendinous junctions (MTJs), with potential therapeutic uses in tendon strengthening and repair
  • possess proangiogenic activity
  • THBS4 regulates skeletal muscle integrity
  • functions in cardiovascular and nervous systems, inflammation, cancer, and the motor unit, which have attracted attention to this extracellular matrix (ECM) protein
  • appears to have some structural functions in ECM
  • is protective in cardiac and skeletal muscle, where it activates an adaptive endoplasmic reticulum (ER) stress response, induces expansion of the ER, and enhances sarcolemmal stability
  • is an important protein in the development of cardiac hypertrophy and aortic dissections in ANGPT2-induced hypertension
  • expression in macrophages increases their accumulation in tissues during the acute inflammatory process
  • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component homotrimer disulfide-linked
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PTBP3 binds to the amphipathic C-terminal peptide of THBS4 and is involved in its mitogenic activity
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    by increased methylation in colorectal cancer (
    tumoral     --over  
    in hepatocellular carcinoma patients, high THBS4 expression was associated with shorter overall and disease-free survival compared with low THBS4 expression
    Susceptibility myocardial infarction
    Variant & Polymorphism SNP A387P significantly associated to myocardial infarction
    Candidate gene
    Marker
  • its level may be a biomarker for the occurrence of colorectal adenomas and carcinoma
  • powerful marker for diffuse-type gastric adenocarcinomas and to provide an initial characterization of its expression in the course of this disease
  • may be an endothelial specific marker of cardiac overload
  • may be an independent prognostic marker for hepatocellular carcinoma patients
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    potential therapeutic target for hepatocellular carcinoma patients
    neuromuscularmyopathy 
    is a potential therapeutic target for muscular dystrophy
    miscelleaneouspain 
    Controlling TSP4 overexpression in peripheral sensory neurons may be a target for analgesic drug development for neuropathic pain
    ANIMAL & CELL MODELS
  • in mice lacking TSP4 (Tsp4&
  • 8315;-/-), hearts failed to acutely augment contractility or activate stretch-response pathways (ERK1/2 and Akt) on exposure to acute pressure overload