PROSITE documentation PDOC51121NtA (N-terminal agrin) domain profile
Agrin is involved in postsynaptic differentiation at the site of nerve-muscle contact. The N-terminal Agrin (NtA) domain is a region of ~135 amino acids required for the localization of agrin to synaptic basal lamina and other basement membranes [1]. Agrin is a heparan sulfate proteoglycan whereof the NtA domain forms the most N-terminal part, followed by 9 Kazal-like domains and 2 LE domains (see <PDOC00961>). The C-terminal part consists of a SEA domain (see <PDOC50024>), 4 EGF-like domains (see <PDOC00021>) and 3 Laminin G domains (see <PDOC50025>), responsible for the clustering of acetylcholine receptors. The NtA domain is the most highly conserved domain in agrin and it binds with the coiled coil domain of laminins [2].
Tertiairy structures show that the NtA domain folds as a β-barrel core flanked by N- and C-terminal helical regions (see <PDB:1PXU>). The core of the domain consists of 5 β-strands that form 2 β-sheets. The structure belongs to the OB fold family and shows similarity with the protease inhibition domain of TIMP-1, suggesting alternative functions for agrin in addition to synaptogenic activity [2,3]. Residues Leu 117 and Val 124 in helix 3 of the NtA domain are essential for binding to the laminin γ1 chain [4].
The profile we developed covers the entire NtA (N-terminal agrin) domain.
Last update:November 2023 / Profile revised.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Denzer A.J. Hauser D.M. Gesemann M. Ruegg M.A. |
| Title | Synaptic differentiation: the role of agrin in the formation and maintenance of the neuromuscular junction. | |
| Source | Cell Tissue Res. 290:357-365(1997). | |
| PubMed ID | 9321698 |
| 2 | Authors | Stetefeld J. Jenny M. Schulthess T. Landwehr R. Schumacher B. Frank S. Ruegg M.A. Engel J. Kammerer R.A. |
| Title | The laminin-binding domain of agrin is structurally related to N-TIMP-1. | |
| Source | Nat. Struct. Biol. 8:705-709(2001). | |
| PubMed ID | 11473262 | |
| DOI | 10.1038/90422 |
| 3 | Authors | Mascarenhas J.B. Ruegg M.A. Sasaki T. Eble J.A. Engel J. Stetefeld J. |
| Title | Structure and laminin-binding specificity of the NtA domain expressed in eukaryotic cells. | |
| Source | Matrix Biol. 23:507-513(2005). | |
| PubMed ID | 15694127 | |
| DOI | 10.1016/j.matbio.2004.11.003 |
| 4 | Authors | Mascarenhas J.B. Ruegg M.A. Winzen U. Halfter W. Engel J. Stetefeld J. |
| Title | Mapping of the laminin-binding site of the N-terminal agrin domain (NtA). | |
| Source | EMBO J. 22:529-536(2003). | |
| PubMed ID | 12554653 | |
| DOI | 10.1093/emboj/cdg041 |
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