Stable Identifier
Reaction [binding]
Homo sapiens
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Agrin (AGRN) is a large multidomain heparan sulfate proteoglycan found in basement membranes, named for its ability to promote aggregation of AChR clusters on the muscle surface directly beneath the nerve terminal (Nitkin et al. 1987). It is a critical organizer of postsynaptic differentiation at the skeletal neuromuscular junction; synaptogenesis is profoundly disrupted in its absence (Gautam et al. 1996). Two alternate N termini exist with differential expression, tissue localization and function. The predominant longer LN form (Burgess et al. 2000) starts with a secretion signal sequence and a laminin-binding domain (Denzer et al. 1995, Kammerer et al. 1999); the shorter SN form associates with the plasma membrane (Burgess et al. 2000, Neumann et al. 2001). Following the SN or LN regions are 8 follistatin repeats, known to bind growth factors and inhibit proteases in other proteins. The central region has two repeats homologous to domain III of laminin. The C-terminal portion, which is responsible for the molecule's known signaling functions, contains four EGF repeats and three LG (G) domains homologous to those found in laminin alpha chains, neurexins and slits (Timpl et al. 2000).

AGRN binds a complex of the tyrosine kinase receptor MuSK, which is responsible for mediating agrin's ability to cluster AChR (Glass et al. 1996, Sanes & Lichtman 2001, Burden et al. 2003) and the coreceptor LRP4 (Kim et al. 2008, Zhang et al. 2008, Zong et al. 2012).

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