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FLASH GENE

Symbol

THBS4

contributors: mct - updated : 21-03-2021

HGNC name	thrombospondin 4
HGNC id	11788

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003248 22 - 3233 NP_003239 - 961 - 2018 30464261 NM_001306213 23 - 3167 NP_001293142 - 870 - 2018 30464261 NM_001306212 23 - 3115 NP_001293141 - 870 - 2018 30464261 NM_001306214 22 - 3109 NP_001293143 - 870 - 2018 30464261

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart valve       Homo sapiens Nervous brain forebrain cerebral cortex   highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Epithelial barrier/lining retinal pigment epithelium (RPE)     Muscular striatum cardiac

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell Homo sapiens Muscular myocyte Homo sapiens Nervous astrocyte 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
	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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer digestive liver potential therapeutic target for hepatocellular carcinoma patients neuromuscular myopathy   is a potential therapeutic target for muscular dystrophy miscelleaneous pain   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