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FLASH GENE

Symbol

THBS1

contributors: mct/npt/pgu - updated : 20-08-2014

HGNC name	thrombospondin 1
HGNC id	11785

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	15q14      Physical location : 39.873.279 - 39.889.667
Synonym symbol(s)	TSP1, THBS, TSP, THBS-1

DNA

TYPE	functioning gene
STRUCTURE	16.39 kb     22 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   HRE
text structure	promoter might have suppressive elements

MAPPING

cloned

Y

linked

Y

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003246 22 - 5820 NP_003237 127.5 1170 - 2008 18757424

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 Endocrine pancreas         Homo sapiens Visual eye anterior segment       Mus musculus

tissue

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

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet cell (alpha,beta...) Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a procollagen homology domain
	a motif within the N-terminal domain specifically promotes the proangiogenic activity of endothelial colony-forming cells
	three type I TSP and seven TSP type III domains
	three EGF-like and one WWFC domain
	a peptide RFYVVMWK (4N-1) located in its C-terminal domain, involved in interaction with CD47

secondary structure

disulfide linked subunits

conjugated

GlycoP

mono polymer

homomer , trimer

HOMOLOGY

interspecies

homolog to murine Thbs1

Homologene

FAMILY

thrombospondin family

CATEGORY

adhesion , signaling

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic,granule
text	matrix protein

basic FUNCTION	matrix protein, involved in platelet aggregation, embryogenesis, morphogenesis, cell adhesion molecule
	major activator of TGFB1
	may play an important role in antitumor immunity
	regulator of tumor growth and metastasis
	can utilizes a novel pathway for its antiangiogenic effect independent of CD36, and suppresses the cell cycle
	play a biologically significant role in tumor vascularization in Ewing's sarcoma (EWS/FLI1 regulates tumor angiogenesis in Ewing's sarcoma via suppression of thrombospondins)
	acting by sequestering and consequently inactivating angiogenic activity of VEGFA
	critical effector of SSTR2 tumor-suppressive activity on pancreatic tumor growth and angiogenesis
	modulates the angiogenic phenotype of cerebral arteriovenous malformation endothelial cells
	endothelial-derived THBS1 activates islet TGFB1 of importance for beta-cells (PMID;
	highly conserved matricellular protein regulating inflammation, angiogenesis and extracellular matrix remodeling
	role of THBS1 in hyperleptinemia-induced atherosclerotic complications '
	matricellular protein that have been shown to regulate cytoskeleton, cell adhesion, and extracellular matrix remodeling

CELLULAR PROCESS

cell communication

PHYSIOLOGICAL PROCESS

coagulation/hemostasis , development

text	homeostasis of the lung

PATHWAY

metabolism

signaling

a component

protein constituent of the extracellular matrix

INTERACTION

DNA

RNA

small molecule

protein	fibrinogen, fribronectin, laminin, collagen type 5, integrin alpha 5 beta1
	interacting with PRMT6 (directly regulates the THBS1 promoter activity and THBS1 is a transcriptional repression target of PRMT6)
	interacting with ADAMTS13 (THBS1 played competitively inhibitory role in ADAMTS13 binding and cleaving of VWF, and the potential competition might happen within A2 and A3 domains)
	new role for THBS1 and CD36 in the activation of the KDR signaling pathway that requires SYK
	PTPRJ functions as a receptor for THBS1 and mediates its inhibition of cell growth
	NOL7 is a tumor suppressor that induces an antiangiogenic phenotype and suppresses tumor growth, in part through upregulation of THBS1
	negative function of PRMT6 on invasion and migration of cancer cells through up-regulation of THBS1 and down-regulation of MMP2 and MMP9
	THBS1-CD36 tandem is another platelet ligand-receptor axis contributing to the maintenance of a stable thrombus
	SEMA3F functions as an unconventional SEMA3 that promotes extraembryonic angiogenesis by inhibiting the MYC-regulated synthesis of THBS1 in visceral yolk sac epithelial cells

cell & other

HMVEC, dermal microvascular endothelial cell

REGULATION

activated by

EGF and TGFB1 (role in modulation of angiogenesis and formation of matrices in tumor stroma )

induced by

ELL (ELL directly induces THBS1 expression)

repressed by

NEDD4

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in liver, brain, pancreas, bone cancer in response to EGF and TGFB1 tumoral     --low   low expressed by hypermethylation in gastric carcinoma constitutional germinal mutation     loss of function in familial pulmonary hypertension constitutional     --low   in HELLP syndrome

Susceptibility

to thoracic aortic aneurysm (TAA) in hypertensive patients

Variant & Polymorphism other	the 3949T-->G (3prime untranslated region) polymorphism is a risk factor for thoracic aortic aneurysm in hypertensive patients

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer bone   potential therapeutic target in Ewing sarcoma

ANIMAL & CELL MODELS

	TSP1-null and TSP2-null mice exhibit lower intraocular pressures
	TSP1-deficient mice were glucose intolerant, despite having an increased beta-cell mass