Thrombospondine 1

THBS1
Structures disponibles PDB Recherche d'orthologue: PDBe RCSB Identifiants PDB 1LSL, 1UX6, 1Z78, 1ZA4, 2ERF, 2ES3, 2OUH, 2OUJ, 3R6B, 5FOE
Identifiants
Aliases	THBS1
IDs externes	OMIM: 188060 MGI: 98737 HomoloGene: 31142 GeneCards: THBS1
Position du gène (Homme) Chr. Chromosome 15 humain[1] Locus 15q14 Début 39,581,079 bp[1] Fin 39,599,466 bp[1]
Position du gène (Souris) Chr. Chromosome 2 (souris)[2] Locus 2 E5|2 59.34 cM Début 117,942,357 bp[2] Fin 117,957,614 bp[2]
Expression génétique Bgee Humain Souris (orthologue) Fortement exprimé dans stromal cell of endometrium muqueuse gastrique péricarde vésicule biliaire left uterine tube tendon calcanéen poumon droit muscle lisse upper lobe of left lung veine cave Fortement exprimé dans stroma of bone marrow calvaria corps du fémur épithélium pigmentaire rétinien granulocyte cumulus cell cordon ombilical skin of external ear fœtus humain endocardial cushion Plus de données d'expression de référence BioGPS Plus de données d'expression de référence
Gene Ontology Fonction moléculaire calcium liaison ionique heparin binding liaison de matrice extracellulaire fibroblast growth factor binding phosphatidylserine binding proteoglycan binding collagen V binding fibrinogen binding low-density lipoprotein particle binding integrin binding laminin binding fibronectin binding identical protein binding transforming growth factor beta binding liaison protéique extracellular matrix structural constituent Composant cellulaire endoplasmic reticulum lumen platelet alpha granule surface cellulaire réticulum endoplasmique exosome matrice extracellulaire secretory granule platelet alpha granule lumen fibrinogène réticulum sarcoplasmique external side of plasma membrane cytoplasme milieu extracellulaire région extracellulaire collagen-containing extracellular matrix Processus biologique positive regulation of transforming growth factor beta receptor signaling pathway cellular response to heat negative regulation of fibrinolysis protein O-linked fucosylation response to progesterone response to magnesium ion positive regulation of translation negative regulation of endothelial cell migration negative regulation of cell-matrix adhesion negative regulation of long-chain fatty acid import across plasma membrane positive regulation of reactive oxygen species metabolic process positive regulation of blood coagulation positive regulation of blood vessel endothelial cell migration positive regulation of macrophage chemotaxis positive regulation of protein kinase B signaling negative regulation of plasminogen activation negative regulation of blood vessel endothelial cell migration negative regulation of extrinsic apoptotic signaling pathway response to endoplasmic reticulum stress positive regulation of endothelial cell apoptotic process response to unfolded protein positive regulation of chemotaxis negative regulation of cGMP-mediated signaling positive regulation of phosphorylation réponse inflammatoire negative regulation of focal adhesion assembly inflammation chronique negative regulation of nitric oxide mediated signal transduction engulfment of apoptotic cell extracellular matrix organization positive regulation of macrophage activation sprouting angiogenesis negative regulation of apoptotic process response to glucose positive regulation of angiogenesis response to calcium ion positive regulation of transforming growth factor beta1 production adhésion cellulaire behavioral response to pain réponse immunitaire negative regulation of interleukin-12 production positive regulation of extrinsic apoptotic signaling pathway via death domain receptors negative regulation of cysteine-type endopeptidase activity involved in apoptotic process response to hypoxia positive regulation of cell migration platelet degranulation negative regulation of endothelial cell chemotaxis negative regulation of endothelial cell proliferation positive regulation of endothelial cell migration negative regulation of fibroblast growth factor receptor signaling pathway peptide cross-linking negative regulation of antigen processing and presentation of peptide or polysaccharide antigen via MHC class II negative regulation of dendritic cell antigen processing and presentation negative regulation of angiogenesis migration cellulaire positive regulation of fibroblast migration response to testosterone cellular response to tumor necrosis factor cellular response to growth factor stimulus positive regulation of transforming growth factor beta production response to mechanical stimulus positive regulation of cell population proliferation positive regulation of smooth muscle cell proliferation regulation of megakaryocyte differentiation negative regulation of cell migration involved in sprouting angiogenesis negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis negative regulation of sprouting angiogenesis Sources:Amigo / QuickGO
Orthologues Espèces Homme Souris Entrez 7057 21825 Ensembl ENSG00000137801 ENSMUSG00000040152 UniProt P07996 P35441 RefSeq (mRNA) NM_003246 NM_011580 NM_001313914 RefSeq (protéine) NP_003237 n/a Localisation (UCSC) Chr 15: 39.58 – 39.6 Mb Chr 2: 117.94 – 117.96 Mb Publication PubMed [3] [4]
Wikidata
Voir/Editer Humain Voir/Editer Souris

La thrombospondine 1 est une protéine appartenant à la famille des thrombospondines. Son gène est THBS1 situé sur le chromosome 15 humain.

Rôles

Elle a un rôle de mécano-récepteur : liée à l'IAP (« integrin associated protein »), sa conformation se modifie en cas de flux sanguin turbulent[5], activant le NOX1[6], modulant par ce biais la vasodilatation des vaisseaux. En particulier, le complexe THBS1-IAP contribue au mécanisme d'une hypertension artérielle pulmonaire[7]. Elle favorise la rigidification vasculaire[8].

Elle a également une action anti-angiogenèse et permet l'activation du TGF bêta[9]. Elle est d'ailleurs l'un des principaux activateurs de ce signal[10]. Elle favorise la formation d'un néo-intima et active les cellules musculaires lisses vasculaires[11].

Son expression est augmentée en cas d'ischémie des membres inférieurs[12].

Elle favorise la cicatrisation ainsi que la fibrose[13].

Notes et références

1. GRCh38: Ensembl release 89: ENSG00000137801 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000040152 - Ensembl, May 2017
3. « Publications PubMed pour l'Homme », sur National Center for Biotechnology Information, U.S. National Library of Medicine
4. « Publications PubMed pour la Souris », sur National Center for Biotechnology Information, U.S. National Library of Medicine
5. Freyberg MA, Kaiser D, Graf R, Buttenbender J, Friedl P, Proatherogenic flow conditions initiate endothelial apoptosis via thrombospondin-1 and the integrin-associated protein, Biochem Biophys Res Commun, 2001;286:141–149
6. Csányi G, Yao M, Rodríguez AI et al. Thrombospondin-1 regulates blood flow via CD47 receptor-mediated activation of NADPH oxidase 1, Arterioscler Thromb Vasc Biol, 2012;32:2966–2973
7. Rogers NM, Sharifi-Sanjani M, Yao M et al. TSP1-CD47 signaling is upregulated in clinical pulmonary hypertension and contributes to pulmonary arterial vasculopathy and dysfunction, Cardiovasc Res, 2017;113:15–29
8. Kim CW, Pokutta-Paskaleva A, Kumar S et al. Disturbed flow promotes arterial stiffening through thrombospondin-1, Circulation, 2017;136:1217-1232
9. Mustonen E, Ruskoaho H, Rysä J, Thrombospondins, potential drug targets for cardiovascular diseases, Basic Clin Pharmacol Toxicol, 2013;112:4–12
10. Crawford SE, Stellmach V, Murphy-Ullrich JE et al. Thrombospondin-1 is a major activator of TGF-beta1 in vivo, Cell, 1998;93:1159–1170
11. Moura R, Tjwa M, Vandervoort P, Cludts K, Hoylaerts MF, Thrombospondin-1 activates medial smooth muscle cells and triggers neointima formation upon mouse carotid artery ligation, Arterioscler Thromb Vasc Biol, 2007;27:2163–2169.
12. Favier J, Germain S, Emmerich J, Corvol P, Gasc JM, Critical overexpression of thrombospondin 1 in chronic leg ischaemia, J Pathol, 2005;207:358–366
13. Sweetwyne MT, Murphy-Ullrich JE, Thrombospondin1 in tissue repair and fibrosis: TGF-β-dependent and independent mechanisms, Matrix Biol, 2012;31:178–186