Alternative titles; symbols
HGNC Approved Gene Symbol: SORCS2
Cytogenetic location: 4p16.1 Genomic coordinates (GRCh38): 4:7,192,538-7,742,827 (from NCBI)
The VPS10 domain-containing receptors, including sortilin (SORT1; 602458) and sortilin-related receptor (SORL1; 602005), derive their name from the yeast vacuolar protein sorting protein-10, which is involved in sorting of carboxy-peptidase Y from the Golgi apparatus to the vacuole. By EST database searching with mouse sequence of 2 VPS10 proteins, Sorcs1 and Sorcs2 (Hermey et al., 1999; Rezgaoui et al., 2001), Hampe et al. (2001) identified 3 novel human VPS10 domain-containing receptors. Two were orthologs of mouse Sorcs1 (606283) and Sorcs2; the third was designated SORCS3 (606285). Hampe et al. (2001) noted that all mammalian VPS10 domains carry an N-terminal signal peptide for translocation into the endoplasmic reticulum. The greatest similarity between the receptors is found in the C-terminal parts of the VPS10 domains, which harbor 12 cysteine residues with a characteristic spacing conserved in all VPS10 proteins from yeast to man. SORCS1 and SORCS3 share the greatest homology. SORCS2 shares the same domain composition, but is less similar. SORT1 and SORTL1 lack the leucine-rich domain of the SORCS proteins, and their VPS10 domains are less related.
Nagase et al. (2000) cloned a human SORCS2 cDNA, which they designated KIAA1329, from a brain cDNA library. By Northern blot analysis, Hampe et al. (2001) detected a 7.5-kb SORCS2 transcript primarily in human brain and kidney.
Gross (2020) mapped the SORCS2 gene to chromosome 4p16.1 based on an alignment of the SORCS2 sequence (GenBank AF286190) with the genomic sequence (GRCh38).
Using electron microscopic analysis, Januliene et al. (2017) showed that most human SORCS2 particles were dimeric, with only a small number of monomeric particles. SORCS2 displayed 2 distinct forms of dimers: one like SORCS1 and SORCS3, and the other, representing the majority, exhibiting a 'yin-yang' symbol-like conformation. Full-length SORCS receptors formed dimers in cells, as both homodimers and heterodimers of Sorcs1, Sorcs2, and Sorcs3 could be isolated from transfected HEK293 cells.
Gross, M. B. Personal Communication. Baltimore, Md. 5/8/2020.
Hampe, W., Rezgaoui, M., Hermans-Borgmeyer, I., Schaller, H. C. The genes for the human VPS10 domain-containing receptors are large and contain many small exons. Hum. Genet. 108: 529-536, 2001. [PubMed: 11499680] [Full Text: https://doi.org/10.1007/s004390100504]
Hermey, G., Riedel, I. B., Hampe, W., Schaller, H. C., Hermans-Borgmeyer, I. Identification and characterization of SorCS, a third member of a novel receptor family. Biochem. Biophys. Res. Commun. 266: 347-351, 1999. [PubMed: 10600506] [Full Text: https://doi.org/10.1006/bbrc.1999.1822]
Januliene, S., Manavalan, A., Ovesen, P. L., Pedersen, K.-M., Thirup, S., Nykjaer, A., Moeller, A. Hidden twins: SorCS neuroreceptors form stable dimers. J. Molec. Biol. 429: 2907-2917, 2017. [PubMed: 28827148] [Full Text: https://doi.org/10.1016/j.jmb.2017.08.006]
Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O. Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 65-73, 2000. [PubMed: 10718198] [Full Text: https://doi.org/10.1093/dnares/7.1.65]
Rezgaoui, M., Hermey, G., Riedel, I. B., Hampe, W., Schaller, H. C., Hermans-Borgmeyer, I. Identification of SorCS2, a novel member of the VPS10 domain containing receptor family, prominently expressed in the developing mouse brain. Mech. Dev. 100: 335-338, 2001. [PubMed: 11165493] [Full Text: https://doi.org/10.1016/s0925-4773(00)00523-2]