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Details on Person UniProt:P07996-2 THBS1

Class:IdReferenceIsoform:8974102
_chainChangeLogsignal peptide:1-18 added on Fri February 17 2017;chain:19-1170 added on Fri February 17 2017
_displayNameUniProt:P07996-2 THBS1
_timestamp2025-08-15 21:27:20
chainsignal peptide:1-18
chain:19-1170
checksum74749B2418E0943B
commentFUNCTION Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions (PubMed:15014436, PubMed:18285447, PubMed:2430973, PubMed:6489349). Multifunctional, involved in inflammation, angiogenesis, wound healing, reactive oxygen species (ROS) signaling, nitrous oxide (NO) signaling, apoptosis, senescence, aging, cellular self-renewal, stemness, and cardiovascular and metabolic homeostasis (PubMed:10613822, PubMed:11134179, PubMed:1371676, PubMed:14568985, PubMed:24511121, PubMed:29042481, PubMed:32679764). Negatively modulates dendritic cell activation and cytokine release, as part of an autocrine feedback loop, contributing to the resolution of inflammation and immune homeostasis (PubMed:14568985). Ligand for receptor CD47 (PubMed:19004835, PubMed:8550562). Modulates nitrous oxide (NO) signaling via CD47, hence playing a role as a pressor agent, supporting blood pressure (By similarity). Plays a role in endothelial cell senescence, acting via CD47, by increasing the abundance and activation of NADPH oxidase NOX1, and so generating excess ROS (PubMed:29042481). Inhibits stem cell self-renewal, acting via CD47 signaling, probably by regulation of the stem cell transcription factors POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 (By similarity). Negatively modulates wound healing, acting via CD47 (By similarity). Ligand for receptor CD36 (PubMed:10613822, PubMed:11134179, PubMed:1371676). Involved in inducing apoptosis in podocytes in response to elevated free fatty acids, acting via CD36 (By similarity). Plays a role in suppressing angiogenesis, acting, depending on context, via CD36 or CD47 (PubMed:10613822, PubMed:11134179, PubMed:1371676, PubMed:32679764). Promotes cellular senescence in a TP53-CDKN1A-RB1 signaling-dependent manner (PubMed:29042481). Ligand for immunoglobulin-like cell surface receptor SIRPA (PubMed:24511121). Involved in ROS signaling in non-phagocytic cells, stimulating NADPH oxidase-derived ROS production, acting via interaction with SIRPA (PubMed:24511121). Plays a role in metabolic dysfunction in diet-induced obesity, perhaps acting by exacerbating adipose inflammatory activity; its effects may be mediated, at least in part, through enhanced adipocyte proliferation (By similarity). Plays a role in ER stress response, via its interaction with the activating transcription factor 6 alpha (ATF6) which produces adaptive ER stress response factors (By similarity). May be involved in age-related conditions, including metabolic dysregulation, during normal aging (PubMed:29042481, PubMed:32679764).SUBUNIT Homotrimer; disulfide-linked (PubMed:101549, PubMed:18285447). Can bind to fibrinogen, fibronectin, laminin, type V collagen and integrins alpha-V/beta-1, alpha-V/beta-3 and alpha-IIb/beta-3 (PubMed:2478219, PubMed:6489349, PubMed:6693501). Binds heparin (PubMed:101549, PubMed:16407063, PubMed:18065761). Interacts (via the C-terminal domain) with CD47 (PubMed:19004835, PubMed:8550562). Interacts (via the TSP type I repeats) with CD36; the interaction conveys an antiangiogenic effect (PubMed:10613822, PubMed:1371676). Interacts (via the TSP type I repeats) with HRG; the interaction blocks the antiangiogenic effect of THBS1 with CD36 (PubMed:11134179). Interacts with ATF6 (via lumenal domain) (By similarity). Interacts with FN1; this interaction is enhanced by TNFAIP6, which may act as a bridging molecule between FN1 and THBS1 (PubMed:18042364). Interacts with SIRPA; the interaction stimulates phosphorylation of SIRPA (PubMed:24511121).INTERACTION Secreted by thrombin-activated platelets and binds to the cell surface in the presence of extracellular Ca(2+) (PubMed:101549, PubMed:6777381). Incorporated into the extracellular matrix (ECM) of fibroblasts (PubMed:6341993). The C-terminal region in trimeric form is required for retention in the ECM (PubMed:18285447). Also detected in the endoplasmic reticulum and sarcoplasmic reticulum where it plays a role in the ER stress response (By similarity).ALTERNATIVE PRODUCTS Expressed by platelets (at protein level) (PubMed:101549). Expressed by monocyte-derived immature and mature dendritic cells (at protein level) (PubMed:14568985).INDUCTION Expression is induced by PGE2, S.aureus and lipopolysaccharide (PubMed:14568985). Induced in arteries and lung parenchyma following injury or stress (PubMed:27742621). Expression in vasculature, including arteries, increases in normal aging (PubMed:29042481, PubMed:32679764).SIMILARITY Belongs to the thrombospondin family.SEQUENCE CAUTION Extended N-terminus.
created[InstanceEdit:8964659] Weiser, JD
descriptionrecommendedName: Thrombospondin-1 alternativeName: fullName evidence="41"Glycoprotein G
geneNameTHBS1
TSP
TSP1
identifierP07996
isoformParent
isSequenceChangedFALSE
keyword3D-structure
Alternative splicing
Angiogenesis
Apoptosis
Calcium
Cell adhesion
Disulfide bond
EGF-like domain
Endoplasmic reticulum
Extracellular matrix
Glycoprotein
Heparin-binding
Inflammatory response
Proteomics identification
Reference proteome
Repeat
Sarcoplasmic reticulum
Secreted
Signal
Unfolded protein response
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
nameTHBS1
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8936976] ENSEMBL:ENSG00000137801 THBS1 [Homo sapiens]
secondaryIdentifierTSP1_HUMAN
A8K6H4
B4E3J7
B9EGH6
Q15667
Q59E99
sequenceLength1170
species[Species:48887] Homo sapiens
variantIdentifierP07996-2
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