Sorting nexin-3 (SNX3)
The protein contains 162 amino acids for an estimated molecular weight of 18762 Da.
Phosphoinositide-binding protein required for multivesicular body formation. Specifically binds phosphatidylinositol 3-phosphate (PtdIns(P3)). Also can bind phosphatidylinositol 4-phosphate (PtdIns(P4)), phosphatidylinositol 5-phosphate (PtdIns(P5)) and phosphatidylinositol 3,5-biphosphate (PtdIns(3,5)P2) (By similarity). Plays a role in protein transport between cellular compartments. Together with RAB7A facilitates endosome membrane association of the retromer cargo-selective subcomplex (CSC/VPS). May in part act as component of the SNX3-retromer complex which mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway (PubMed:21725319, PubMed:24344282, PubMed:30213940). Promotes stability and cell surface expression of epithelial sodium channel (ENAC) subunits SCNN1A and SCNN1G (By similarity). Not involved in EGFR degradation. Involved in the regulation of phagocytosis in dendritic cells possibly by regulating EEA1 recruitment to the nascent phagosomes (PubMed:23237080). Involved in iron homeostasis through regulation of endocytic recycling of the transferrin receptor TFRC presumably by delivering the transferrin:transferrin receptor complex to recycling endosomes; the function may involve the CSC retromer subcomplex (By similarity). In the case of Salmonella enterica infection plays arole in maturation of the Salmonella-containing vacuole (SCV) and promotes recruitment of LAMP1 to SCVs (PubMed:20482551). (updated: April 7, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Endocytic recycling
Hemoglobin biosynthetic process
Intralumenal vesicle formation
Late endosome to Golgi transport
Membrane invagination
Negative regulation of early endosome to late endosome transport
Negative regulation of phagocytosis
Negative regulation of protein catabolic process
Negative regulation of protein transport
Negative regulation of viral entry into host cell
Positive regulation of neuron projection development
Protein deubiquitination
Protein to membrane docking
Protein transport
Regulation of cellular protein metabolic process
Regulation of intracellular protein transport
Regulation of Wnt signaling pathway
Response to bacterium
Transferrin transport
Vesicle organization
Wnt signaling pathway
The reference OMIM entry for this protein is 601349
Microphthalmia, syndromic 8; mcops8
Microcephaly, microphthalmia, ectrodactyly of lower limbs, and prognathism; mmep
CLINICAL FEATURES
Viljoen and Smart (1993) described a woman with mental retardation, borderline microcephaly, microphthalmia, prognathism, cleft lip and palate, ectrodactyly of the feet, and premature aging of the skin. Her karyotype showed a de novo translocation 46,XX,t(6;13)(q21;q12). Suthers and Morris (1996) reported a mentally retarded man with borderline microcephaly, microphthalmia, microcornea, prognathism, wide gap between his upper central incisors, ventricular septal defect, split-feet, cryptorchidism, and normal karyotype. They proposed that their patient and that of Viljoen and Smart (1993) represented a distinct syndrome which could be related to mutation in a gene located on either 6q21 or 13q12. Van den Ende et al. (1996) described the association of congenital heart defects and split-feet in 4 infants who had the additional manifestations of short palpebral fissures and micrognathia; see 601348. It is possible that the various facial abnormalities reflect age-related differences.CYTOGENETICS
In the patient with MMEP and translocation 46,XX,t(6;13)(q21;q12) reported by Viljoen and Smart (1993), Vervoort et al. (2002) localized the breakpoint on chromosome 6q21 close to marker D6S1250. Cloning of the breakpoint fragment allowed localization of the der(13) breakpoint close to a marker in the region 13q11-q12. Sequencing of the chromosome 13 breakpoint confirmed that the translocation was balanced, with no missing or duplicated material. No gene on chromosome 13 appeared to be disrupted, whereas the SNX3 gene on 6q21 was. Mutation screening of another sporadic case of MMEP failed to detect any point mutations or deletions in the SNX3 coding sequence. Because of the possibility of positional effect, Vervoort et al. (2002) suggested that another candidate gene in the vicinity of the chromosome 6 breakpoint may have been responsible for MMEP in the original patient or, just as likely, the MMEP phenotype in the 2 patients resulted from different genetic causes. ... More on the omim web site
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601349 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed