Table 1. Summary of SNX family.
| Subfamilies | Members | Characteristics of structure | Typical examples involving in intracellular physiological functions |
|---|---|---|---|
| SNX-BAR | SNX1, SNX2, SNX4, SNX5, SNX6, SNX7, SNX8, SNX9, SNX18, SNX30, SNX32, SNX33 | In addition to the SNX-PX domain, these proteins have a C-terminal BAR domain comprising three α-helices capable of dimerizing with another BAR domain to form a rigid banana-shaped structure. | SNX1, SNX2, SNX5, and SNX6 are involved in the endosomal membrane sorting processes [25,27]. |
| Their BAR domains allow SNX-BARs to form specific homo- and hetero-dimers (e.g. SNX1 and SNX2; SNX5 and SNX6). | SNX4 prevents BACE1 trafficking to the lysosomal degradation system [40]. | ||
| SNX6, a member of the IGF1–IGF1 receptor pathway, regulates the signaling of IGF-1 stimulation [41]. | |||
| SNX9 and SNX18 are associated with clathrin-mediated and independent endocytosis [30–32]. | |||
| SNX9, SNX18, and SNX33 are required for mitosis through both endocytosis- dependent and -independent processes [103]. | |||
| SNX-PX | SNX3, SNX10, SNX11, SNX12, SNX16, SNX20, SNX21, SNX22, SNX24, SNX29 | The subfamily of proteins is a relatively poorly characterized group of molecules, which have not any conserved domains outside the defining PX domain. | SNX3-retromer is indentified as a distinct form of the mammalian retromer complex [24]. |
| These proteins are of various lengths and typically contain long extended sequences with no predicted secondary structure. | SNX11 promotes the trafficking of TRPV3 from the plasma membrane to lysosomes for degradation [35]. | ||
| SNX10 controls mTOR activation in colorectal cancer [42]. | |||
| SNX16 functions in the trafficking of proteins between the early and late endosomal compartments, and plays a role in the regulation of late endosome membrane dynamics [104,105]. | |||
| SNX-FERM | SNX17, SNX27, SNX31 | The three proteins contain a typical C-terminal FERM domain, which is comprised of approximately 300 amino acids. In addition, SNX27 possesses an N-terminal PDZ domain. The sequence homology of the PX-associated FERM domains with the canonical FERM domain is low. | SNX27-retromer is an important form of the mammalian retromer complex [26]. |
| SNX17 prevents lysosomal degradation of β1 integrins by binding to the β1-integrin tail [38]; SNX17 also inhibits the movement of P-selectin into lysosomes [39];. | |||
| SNX31 mediates the endocytic degradation of proteins such as uroplakins [106]. | |||
| SNX-PXA -RGS-PXC | SNX13, SNX14, SNX19, SNX25 | Each member possesses two putative N-terminal transmembrane helices. SNX13, SNX14, and SNX25 have a long C-terminal structure containing four modular domains (PXA-RGS-PX-PXC); however, SNX19 has only three (PXA-PX-PXC). | Snx13 is involved in the degradative sorting of apoptosis repressor with caspase recruitment domain [93]. |
| SNX14 is a dual endogenous negative regulator in 5-HT6R-mediated signaling pathway [107]. | |||
| SNX25 negatively regulates TGF-β signaling via enhancing the receptor degradation [108]. | |||
| Other unique SNX subfamilies (SNX15-MIT and SNX23) | SNX15 | SNX15, first identified via database searches for SNX1 homologs, includes a C-terminal MIT domain. | SNX15 is associated with the endocytic and endosomal sorting [109,110]. |
| SNX23 (also known as kinesin-family protein 16B, KIF16B) | SNX23, a member of the kinesin family, contains kinesin motor, a putative FHA domain, and coiled coil dimerization domains. | SNX23 regulates receptor recycling and degradation [111]. |
Abbreviations: BACE1, β-site amyloid precursor protein-cleaving enzyme 1; BAR, Bin/Amphiphysin/Rvs domain; FERM, protein 4.1/ezrin/radixin/moesin domain; FHA, forkhead associated domain; IGF1, insulin-like growth factor 1; MIT, microtubule interacting and trafficking domain; mTOR, mammalian target of rapamycin; PDZ, postsynaptic density 95/discs large/zonula occludens domain; PX, phagocyte oxidase (phox) homology domain; PXA, PX-associated domain A; PXC, PX-associated domain C; RGS, regulator of G-protein signaling domain; SNX, sorting nexin; TGF-β, transforming growth factor-β; TRPV3, transient receptor potential vanilloid channel 3.