Sorting nexin-6 (SNX6)
The protein contains 406 amino acids for an estimated molecular weight of 46649 Da.
Involved in several stages of intracellular trafficking. Interacts with membranes phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-bisphosphate (Probable). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex (PubMed:19935774). The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC) (Probable). Does not have in vitro vesicle-to-membrane remodeling activity (PubMed:23085988). Involved in retrograde endosome-to-TGN transport of lysosomal enzyme receptor IGF2R (PubMed:17148574). May function as link between transport vesicles and dynactin (Probable). Negatively regulates retrograde transport of BACE1 from the cell surface to the trans-Golgi network (PubMed:20354142). Involved in E-cadherin sorting and degradation; inhibits PIP5K1C isoform 3-mediated E-cadherin degradation (PubMed:24610942). In association with GIT1 involved in EGFR degradation. Promotes lysosomal degradation of CDKN1B (By similarity). May contribute to transcription regulation (Probable). (updated: March 4, 2015)
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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
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
Cellular response to amyloid-beta
Endocytosis
Intracellular protein transport
Negative regulation of epidermal growth factor-activated receptor activity
Negative regulation of neuron apoptotic process
Negative regulation of transcription, DNA-templated
Negative regulation of transforming growth factor beta receptor signaling pathway
Regulation of macroautophagy
Retrograde transport, endosome to Golgi
Vesicle organization
The reference OMIM entry for this protein is 606098
Sorting nexin 6; snx6
DESCRIPTION
SNX6 if a member of the sorting nexin family of molecules that contain a phox homology (PX) domain and share homology with several yeast proteins involved in protein trafficking (Parks et al., 2001).CLONING
Using a yeast 2-hybrid screen with SMAD1 (601595) as bait, Parks et al. (2001) identified sorting nexin-6 and cloned a full-length cDNA from a human heart cDNA library. The deduced 406-amino acid protein shares 66% sequence identity with the SNX5 (605937) protein. Northern blot analysis detected wide expression of major 2.2-kb and minor 3.0-kb transcripts, with highest levels in heart, skeletal muscle, and placenta and low levels in lung and liver.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the SNX6 gene to chromosome 14 (TMAP WI-6202).GENE FUNCTION
Parks et al. (2001) found that the interaction of SNX6 with Smad1 was very weak, but immunoprecipitation studies showed that SNX6 interacts strongly through its PX domain with members of the transforming growth factor-beta family of receptor serine-threonine kinases, including ActRIIB (602730), TGFBR1 (see 190181), and TGFBR2 (see 190182). Parks et al. (2001) found that SNXs 1-4 (see 601272) also interacted with the TGFB receptor family, showing different receptor preferences. Conversely, SNX6 behaved similarly to the other SNX proteins in its interactions with receptor tyrosine kinases, including epidermal growth factor (131550), platelet-derived growth factor (see 173490), insulin (147670), and the long form of the leptin receptor (601007). Strong heteromeric interactions were seen among SNX1 (601272), SNX2 (605929), SNX4 (605931) and SNX6, suggesting the formation in vivo of oligomeric complexes. Both the PX domain and the coiled-coil regions of the molecules may contribute to the heterooligomerization. Indirect immunofluorescence studies demonstrated that SNX6 colocalizes with other SNXs specifically in the cell cytoplasm. 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 (601272, 605929) (C. elegans homolog snx1) and 5 and 6 (605937) (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. ... More on the omim web site
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 606098 was added.