{PDOC51121} {PS51121; NTA} {BEGIN} ***************************************** * NtA (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 ). The C-terminal part consists of a SEA domain (see ), 4 EGF-like domains (see ) and 3 Laminin G domains (see ), 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 beta-barrel core flanked by N- and C-terminal helical regions (see ). The core of the domain consists of 5 beta-strands that form 2 beta-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 gamma1 chain [4]. The profile we developed covers the entire NtA (N-terminal agrin) domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: November 2023 / Profile revised. [ 1] Denzer A.J., Hauser D.M., Gesemann M., Ruegg M.A. "Synaptic differentiation: the role of agrin in the formation and maintenance of the neuromuscular junction." Cell Tissue Res. 290:357-365(1997). PubMed=9321698 [ 2] Stetefeld J., Jenny M., Schulthess T., Landwehr R., Schumacher B., Frank S., Ruegg M.A., Engel J., Kammerer R.A. "The laminin-binding domain of agrin is structurally related to N-TIMP-1." Nat. Struct. Biol. 8:705-709(2001). PubMed=11473262; DOI=10.1038/90422 [ 3] Mascarenhas J.B., Ruegg M.A., Sasaki T., Eble J.A., Engel J., Stetefeld J. "Structure and laminin-binding specificity of the NtA domain expressed in eukaryotic cells." Matrix Biol. 23:507-513(2005). PubMed=15694127; DOI=10.1016/j.matbio.2004.11.003 [ 4] Mascarenhas J.B., Ruegg M.A., Winzen U., Halfter W., Engel J., Stetefeld J. "Mapping of the laminin-binding site of the N-terminal agrin domain (NtA)." EMBO J. 22:529-536(2003). PubMed=12554653; DOI=10.1093/emboj/cdg041 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}