D
IPR056217

THSD1, N-terminal domain

InterPro entry
Short nameTHSD1_N

Description

This domain is found N-terminal in human Thrombospondin type-1 domain-containing protein 1 (THSD1) and similar proteins mainly found in vertebrates. THSD1 is involved in endothelial cell to extracellular matrix adhesion
[2]
. THSD1 forms a multimeric protein complex with FAK/talin/vinculin, wherein THSD1 promotes talin binding to FAK but not to vinculin, a key step in nascent adhesion assembly
[3]
. The domain represented by this entry is predicted to adopt Ig-like β-sandwich.

Thrombospondins are multimeric multidomain glycoproteins that function at cell surfaces and in the extracellular matrix milieu. They act as regulators of cell interactions in vertebrates. They are divided into two subfamilies, A and B, according to their overall molecular organisation. The subgroup A proteins TSP-1 and -2 contain an N-terminal domain, a VWFC domain, three TSP1 repeats, three EGF-like domains, TSP3 repeats and a C-terminal domain. They are assembled as trimer. The subgroup B thrombospondins, designated TSP-3, -4, and COMP (cartilage oligomeric matrix protein, also designated TSP-5) are distinct in that they contain unique N-terminal regions, lack the VWFC domain and TSP1 repeats, contain four copies of EGF-like domains, and are assembled as pentamers
[1]
. EGF, TSP3 repeats and the C-terminal domain are thus the hallmark of a thrombospondin.

References

1.Thrombospondins: multifunctional regulators of cell interactions. Adams JC. Annu. Rev. Cell Dev. Biol. 17, 25-51, (2001). View articlePMID: 11687483

2.THSD1 (Thrombospondin Type 1 Domain Containing Protein 1) Mutation in the Pathogenesis of Intracranial Aneurysm and Subarachnoid Hemorrhage. Santiago-Sim T, Fang X, Hennessy ML, Nalbach SV, DePalma SR, Lee MS, Greenway SC, McDonough B, Hergenroeder GW, Patek KJ, Colosimo SM, Qualmann KJ, Hagan JP, Milewicz DM, MacRae CA, Dymecki SM, Seidman CE, Seidman JG, Kim DH. Stroke 47, 3005-3013, (2016). View articlePMID: 27895300

3.The Intracranial Aneurysm Gene THSD1 Connects Endosome Dynamics to Nascent Focal Adhesion Assembly. Rui YN, Xu Z, Fang X, Menezes MR, Balzeau J, Niu A, Hagan JP, Kim DH. Cell Physiol Biochem 43, 2200-2211, (2017). View articlePMID: 29069646

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