Laminins are large heterotrimeric glycoproteins involved in basement membrane function [ (PUBMED:15037599) ]. The Laminin G or LNS domain (for Laminin-alpha, Neurexin and Sex hormone-binding globulin) is an around 180 amino acid long domain found in a large and diverse set of extracellular proteins [ (PUBMED:1975589) (PUBMED:9480764) ]. The laminin globular (G) domain can be found in one to several copies in various laminin family members, including a large number of extracellular proteins. The C terminus of the laminin alpha chain contains a tandem repeat of five laminin G domains, which are critical for heparin-binding and cell attachment activity [ (PUBMED:10747011) ]. Laminin alpha4 is distributed in a variety of tissues including peripheral nerves, dorsal root ganglion, skeletal muscle and capillaries; in the neuromuscular junction, it is required for synaptic specialisation [ (PUBMED:15823034) ]. The structure of the laminin-G domain has been predicted to resemble that of pentraxin [ (PUBMED:9480764) ].
Laminin G domains can vary in their function, and a variety of binding functions have been ascribed to different LamG modules. For example, the laminin alpha1 and alpha2 chains each have five C-teminal laminin G domains, where only domains LG4 and LG5 contain binding sites for heparin, sulphatides and the cell surface receptor dystroglycan [ (PUBMED:10747011) ]. Laminin G-containing proteins appear to have a wide variety of roles in cell adhesion, signalling, migration, assembly and differentiation. Proteins with laminin-G domains include:
Laminin.
Merosin.
Agrin.
Neurexins.
Vitamin K dependent protein S.
Sex steroid binding protein SBP/SHBG.
Drosophila proteins Slit, Crumbs, Fat.
several proteoglycan precursors.
Family alignment:
There are 10670 TSPN domains in 10645 proteins in SMART's nrdb database.
Click on the following links for more information.
Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing TSPN domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with TSPN domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing TSPN domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
Merging extracellular domains: fold prediction for laminin G-like and amino-terminal thrombospondin-like modules based on homology to pentraxins.
J Mol Biol. 1998; 275: 725-30
Display abstract
Using a new method for construction and database searches of sequence consensus strings, we have identified a new superfamily of protein modules comprising laminin G, thrombospondin N and the pentraxin families. The conserved patterns correspond mainly to hydrophobic core residues located in central beta strands of the known three-dimensional structures of two pentraxins, the human C-reactive protein and the serum amyloid P-component. Thus, we predict a similar jellyroll fold for all members of this superfamily. In addition, the conservation of two exposed aspartate residues in the majority of superfamily members suggests hitherto unrecognised functional sites.
Decorin inhibits cell attachment to thrombospondin-1 by binding to a KKTR-dependent cell adhesive site present within the N-terminal domain of thrombospondin-1.
J Cell Biochem. 1997; 67: 75-83
Display abstract
Skin decorin (DCN) is an antiadhesive dermatan sulfate-rich proteoglycan that interacts with thrombospondin-1 (TSP) and inhibits fibroblast adhesion to TSP [Winnemoller et al., 1992]. Molecular mechanisms by which DCN interacts with TSP and inhibits cell adhesion to TSP are unknown. In the present study, we showed that skin DCN and bone DCN (chondroitin sulfate-rich proteoglycan) were quantitatively identical with respect to their ability to interact with TSP. Using a series of fusion proteins corresponding to the different structural domains of TSP, binding of [125I]DCN to TSP was found to be dependent of the N-terminal domain and, to a lesser extent, of the type 1 repeats and the C-terminal domain of TSP. In addition, heparan sulfate drastically inhibited [125I]DCN binding to solid-phase adsorbed TSP (80% inhibition), suggesting that DCN could bind to the N-terminal domain of TSP through interaction with heparin-binding sequences. To address this question, a series of synthetic peptides, overlapping heparin-binding sequences ARKGSGRR (residues 22-29), KKTR (residues 80-83) and RLRIAKGGVNDN (residues 178-189), were synthesized and tested for their ability to interact with DCN. [125I]DCN interacted only with peptides VDAVRTEKGFLLLASLRQMKKTRGT and KKTRGTLLALERKDHS containing the heparin-binding consensus sequence KKTR. These peptides contained glycosaminoglycan-dependent and -independent binding sites because [125I]DCN binding to VDAVRTEKGFLLLASLRQMKKTRGT and KKTRGTLLALERKDHS was partially reduced upon removal of the glycosaminoglycan chain (65% and 46% inhibition, respectively). [125I]DCN poorly bound to subpeptide MKKTRG and did not bind at all to subpeptides VDAVRTEKGFLLLASLRQ and TLLALERKDHS, suggesting that heparin-binding sequence MKKTRG constituted a DCN binding site when flanked with peptides VDAVRTEKGFLLLASLRQ and TLLALERKDHS. The sequence VDAVRTEKGFLLLASLRQMKKTRGTLLALERKDHS constitutes a cell adhesive active site in the N-terminal domain of TSP [Clezardin et al., 1997], and DCN inhibited the attachment of fibroblastic and osteoblastic cells to peptides VDAVRTEKGFLLLASLRQMKKTRGT and KKTRGTLLALERKDHS by about 50 and 80%, respectively. Although fibroblastic cells also attached to type 3 repeats and the C-terminal domain of TSP, DCN only inhibited cell attachment to the C-terminal domain. Overall, these data indicate that modulation by steric exclusion of cell adhesion to a KKTR-dependent cell adhesive site present within the N-terminal domain of TSP could explain the antiadhesive properties of DCN.
Collagens are typical mosaic proteins containing a number of shuffled domains. These domains have been classified by sequence similarity in order to characterize their structural and functional relationships to other proteins. This analysis provides an overview of homologies of collagen domains. It also reveals two new relationships: (i) a module common to type V, IX, XI, and XII collagens was found to be homologous to the heparin binding domain of thrombospondin; (ii) the modular architecture of a human type VII collagen fragment was identified. Its N-terminal globular domain contains fibronectin type III repeats located adjacent to a Von Willebrand factor type A module. The proposed structural similarities point to analogous subfunctions of the respective domains in otherwise distinct proteins.
Metabolism (metabolic pathways involving proteins which contain this domain)
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with TSPN domain which could be assigned to a KEGG orthologous group, and not all proteins containing TSPN domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
