GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms.

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara.

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods.

PMID:11943589

Corneal stromal cells (keratocytes) express thrombospondins 2 and 3 in wound repair phenotype.

TSP-3 is expressed in cultured keratocytes in wound repair phenotype

"Cultured keratocytes contained messenger RNA (mRNA) for TSP-2 and TSP-3 (in addition to TSP-1), but not for TSP-4 or cartilage oligomeric matrix protein (COMP; TSP-5)"
Perinuclear immunoreactivity pattern observed

"The distribution of keratocyte TSP-2 and TSP-3 immunoreactivity had some similarities to that of TSP-1"
Not detected in normal corneal stroma

"like TSP-1, neither protein could be detected in the cells of the normal corneal stroma"

PMID:28327460

Comprehensive proteomic characterization of stem cell-derived extracellular matrices.

THBS3 identified in ECM produced by MSCs and fibroblasts

"Here, we characterized and compared the protein composition of ECM produced in vitro by bone marrow-derived MSC, adipose-derived MSC and neonatal fibroblasts from different donors, employing quantitative proteomic methods"

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

High-throughput interactome study

"Interactome maps are valuable resources to elucidate protein function and disease mechanisms"

PMID:7558000

Structure and organization of the human thrombospondin 3 gene (THBS3).

THBS3 gene composed of 23 exons

"Analysis of cDNA and genomic sequences showed the THBS3 gene to be composed of 23 exons"
Encodes 956 amino acid polypeptide

"The cDNA encodes a polypeptide of 956 amino acids that is highly acidic"
Contains seven type III (Ca2+-binding) repeats

"This region corresponds to seven type III (Ca(2+)-binding) repeats, a feature shared with other thrombospondins"

PMID:8288588

Thrombospondin 3 is a developmentally regulated heparin binding protein.

THBS3 is an oligomeric heparin-binding protein

"Metabolic labeling and immunoprecipitation analysis of cells transfected with a TSP3 expression vector revealed it to be an oligomeric heparin binding protein present in both the cell layer and medium"
Developmentally regulated expression in cartilage, lung, gut, CNS

"Finally, a combination of in situ hybridization and immunocytochemistry demonstrated TSP3 to be expressed in a temporal and spatial manner during murine embryogenesis, especially in the gut, cartilage, lung, and central nervous system"

Reactome:R-HSA-382054

PDGF binds to extracellular matrix proteins

Thrombospondins bind PDGF in ECM context

"PDGF binds to various types of collagens, thrombospondin and osteopontin; however, the major component of the matrix involved in PDGF binding is likely to be haparan sulphate"

file:human/THBS3/THBS3-deep-research-perplexity.md

Deep research on THBS3 function

Pentameric matricellular glycoprotein
Contains EGD motif instead of RGD (unique among thrombospondins)
Regulates skeletal maturation
Role in cardiac pathophysiology via integrin trafficking
Knockout mice show accelerated bone ossification

file:human/THBS3/THBS3-deep-research-falcon.md

Falcon (Edison) deep research report on human THBS3 (thrombospondin-3, P49746)

THBS3 is a secreted matricellular ECM glycoprotein and a Group B (pentameric) thrombospondin, grouped with THBS4 and THBS5/COMP.

"THBS3 encodes thrombospondin-3 (TSP3), a secreted matricellular extracellular-matrix (ECM) glycoprotein in the thrombospondin family, specifically the pentameric (Group B) thrombospondins (TSP3/4/5)"
TSP3 is a pentamer assembled via amino-terminal disulfide bonds and carries a conserved C-terminal calcium-binding signature region.

"TSP3 is a pentamer formed via amino-terminal disulfide bonding and contains a conserved calcium-binding signature region in the C-terminus"
Group B thrombospondins are pentameric extracellular calcium-binding proteins whose architecture supports multivalent ECM and receptor interactions.

"Group B thrombospondins are described as pentameric extracellular proteins with calcium-binding architecture that supports multivalent ECM/receptor interactions"
In developing bone, TSP3 is localized to the growth plate proliferating zone and perichondrium, and all five thrombospondins occur in articular cartilage.

"In developing bone, TSP3 expression is localized to the growth plate proliferating zone and perichondrium, and all five thrombospondins are found in articular cartilage"
Mouse TSP3 knockout accelerates ossification of the femoral head and transiently increases cortical moment of inertia, increasing femur bending strength.

"TSP3 knockout causes accelerated ossification of the femoral head and transient increases in cortical moment of inertia that increase femur bending strength"
THBS3 acts as a pseudorabies virus (PRV) coreceptor, directly binding viral glycoprotein D via its N- and C-terminal regions to promote attachment, fusion, and entry (experimental cell systems; veterinary pathogen).

"THBS3 directly binds PRV glycoprotein D through its N- and C-terminal regions and promotes binding/fusion/entry"
In a 2024 osteoarthritis preprint, recombinant THBS3 increased catabolic enzymes (MMP-13, ADAMTS-5), suppressed Aggrecan, and promoted endothelial migration/tube formation, linked to TGF-beta signaling (preprint; requires peer-reviewed confirmation).

"Recombinant THBS3 increased catabolic enzymes (MMP-13, ADAMTS-5), suppressed Aggrecan, and promoted endothelial migration/tube formation relevant to cartilage vascularization/osteogenesis coupling in OA models"
A 2024 cardiovascular review proposes TSP3 may worsen cardiac pathology by inhibiting integrin signaling and destabilizing membranes, and can activate ER stress via ATF6alpha binding.

"TSP3 may worsen cardiac pathology by inhibiting integrin signaling and destabilizing membranes"
A 2024 SMR/Mendelian-randomization analysis associated higher blood THBS3 expression with lower gout risk.

"higher THBS3 expression associated with lower gout risk"