FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in SH3 and multiple ankyrin repeat domains protein 2 (SHANK2)
SHANK2, also termed cortactin-binding protein 1 (CortBP1), or proline-rich synapse-associated protein 1, is a postsynaptic density (PSD)-associated scaffolding proteins at the excitatory synapse that interconnects neurotransmitter receptors and cell adhesion molecules by direct and indirect interactions with numerous other PSD-associated proteins. It is strongly expressed in the cerebellum. Moreover, SHANK2 acts as a component of the albumin endocytic pathway in podocytes, and regulates renal albumin endocytosis. It also associates with and regulates Na+/H+ exchanger 3 (NHE3) and is involved in the fine regulation of transepithelial salt and water transport through affecting NHE3 expression and activity. Mutations in the SHANK2 synaptic scaffolding gene may lead to autism spectrum disorder and mental retardation. SHANK2 contains an N-terminal F0 domain of FERM (Band 4.1, ezrin, radixin, moesin), six ankyrin (ANK) repeats, one SH3 (Src homology 3) domain, one PDZ (PSD-95, Dlg, and ZO-1/2, also termed DHR or GLGF) domain, and a C-terminal SAM (sterile alpha motif) domain. This family corresponds to the F0 domain that adopts a ubiquitin-like fold.
Comment:2 (K27/R, K48/R Ub numbering) of the 7 lysines involved in chain linkage in ubiquitin (K6, K11, K27, K29, K33, K48, or K63, Ub numbering) are conserved in some members of this family; may have roles other than chain linkage