FIGURE 3.

Structural organization of human NKCC1. 2-dimensional (left) and 3-dimensional (right) organization of human NKCC1 (A) according to Zhao et al. (2022) (PDB: 7S1X). NKCC1 consists of 12 transmembrane domains (TMs) and two intracellular termini. A large extracellular loop is located between transmembrane domains 7 and 8 (EL4). Phosphorylation sites that increase NKCC1 activity upon phosphorylation are marked as blue stars (Thr²⁰³, Thr²⁰⁷, Thr²¹², and Thr²¹⁷). Human pathogenic variants of NKCC1 associated with autism spectrum disorder, schizophrenia, multisystem dysfunction, spastic quadriparesis, and hearing impairment are depicted as red dots in human NKCC1 (His^186fs17, Tyr^199Cys, Ala^327Val, Asn^376Leu, Ala^379Leu, Arg^410Glu, Trp^892*, Gln^979Lys, Asn^981Tyr, Pro^988Ser, Pro^988Thr, Thr^411Asn, 2930.2A > G, Val^{1026F fs*2}). The 3D reconstruction of NKCC1 was generated using cryo-EM (Zhao et al., 2022). 3D visualization was performed using Mol* Viewer in PDB (Sehnal et al., 2021).