Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol THBS4 contributors: mct - updated : 21-03-2020
HGNC name thrombospondin 4
HGNC id 11788
DNA
TYPE functioning gene
STRUCTURE 92.46 kb     22 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Binding site
text structure calcium and heparin binding sites
MAPPING cloned Y linked   status provisional
Map cen - D5S1977 - D5S1962 - ARSB - THBS4 - D5S620 - D5S2029 - D5S627 - D5S626 - HAPLN1 - D5S469 - D5S428 - qter
Authors GeneMap
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
22 - 3233 - 961 - 2018 30464261
23 - 3167 - 870 - 2018 30464261
23 - 3115 - 870 - 2018 30464261
22 - 3109 - 870 - 2018 30464261
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheartvalve    Homo sapiens
Nervousbrainforebraincerebral cortex highly Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivebone   
Epithelialbarrier/liningretinal pigment epithelium (RPE)  
Muscularstriatumcardiac  
cells
SystemCellPubmedSpeciesStageRna symbol
Cardiovascularendothelial cell Homo sapiens
Muscularmyocyte Homo sapiens
Nervousastrocyte Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
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
  • 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