HGNC Approved Gene Symbol: SNX2
Cytogenetic location: 5q23.2 Genomic coordinates (GRCh38) : 5:122,774,996-122,834,543 (from NCBI)
SNX2 is a member of the sorting nexin family of molecules that contain an approximately 100-amino acid region termed the phox homology (PX) domain (Haft et al., 1998).
By database searching with the sequence of sorting nexin-1 (SNX1; 601272), Haft et al. (1998) obtained several human EST clones, determined their nucleotide sequences, and constructed full-length cDNAS corresponding to an isoform of SNX1 (SNX1A), SNX2, SNX3 (605930), and SNX4 (605931). The SNX2 cDNA encodes a deduced 519-amino acid protein that shares 63% sequence identity with SNX1. Northern blot analysis detected SNX2 transcripts of approximately 3.1 and 2.4 kb in all tissues tested, with highest expression in spleen, heart, skeletal muscle, and peripheral leukocytes, and low expression in kidney, liver, and brain.
Stumpf (2024) mapped the SNX2 gene to chromosome 5q23.2 based on an alignment of the SNX2 sequence (GenBank NM_003100) with the genomic sequence (GRCh38).
By Western blot analysis, Haft et al. (1998) showed that SNX1, SNX1A, SNX2, and SNX4 are associated predominantly with membranes, whereas SNX3 is found mainly in the cytosol. SNX2 is able to oligomerize with itself and forms heteromeric complexes with SNX1, SNX1A, and SNX4, but not with SNX3. When expressed in COS-7 cells, epitope-tagged SNX1, SNX1A, SNX2, and SNX4 coimmunoprecipitated with receptor tyrosine kinases for EGF (131550), platelet-derived growth factor (see 173490), and insulin (147670). They also associated with the long isoform of the leptin receptor (601007) but not with the short and medium isoforms. Based on the functions of their yeast homologs, Haft et al. (1998) suggested that mammalian sorting nexins function in intracellular trafficking of proteins to various organelles.
The cell surface receptor CED1 (107770) mediates apoptotic cell recognition by phagocytic cells, enabling cell corpse clearance in C. elegans. Chen et al. (2010) found that the C. elegans intracellular protein sorting complex, retromer, was required for cell corpse clearance by mediating the recycling of CED1. The mammalian retromer complex contains sorting nexins 1 and 2 (C. elegans homolog snx1) and 5/6 (605937, 606098) (C. elegans homolog snx6). Retromer was recruited to the surfaces of phagosomes containing cell corpses, and its loss of function caused defective cell corpse removal. The retromer probably acted through direct interaction with CED1 in the cell corpse recognition pathway. In the absence of retromer function, CED1 associated with lysosomes and failed to recycle from phagosomes and cytosol to the plasma membrane. Thus, Chen et al. (2010) concluded that retromer is an essential mediator of apoptotic cell clearance by regulating phagocytic receptor(s) during cell corpse engulfment.
Chen, D., Xiao, H., Zhang, K., Wang, B., Gao, Z., Jian, Y., Qi, X., Sun, J., Miao, L., Yang, C. Retromer is required for apoptotic cell clearance by phagocytic receptor recycling. Science 327: 1261-1264, 2010. [PubMed: 20133524] [Full Text: https://doi.org/10.1126/science.1184840]
Haft, C. R., de la Luz Sierra, M., Barr, V. A., Haft, D. H., Taylor, S. I. Identification of a family of sorting nexin molecules and characterization of their association with receptors. Molec. Cell. Biol. 18: 7278-7287, 1998. [PubMed: 9819414] [Full Text: https://doi.org/10.1128/MCB.18.12.7278]
Stumpf, A. M. Personal Communication. Baltimore, Md. 09/03/2024.