Sorting nexin-5 (SNX5)

The protein contains 404 amino acids for an estimated molecular weight of 46816 Da.

 

Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) (PubMed:15561769). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. 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 transport of lysosomal enzyme receptor IGF2R (PubMed:17148574, PubMed:18596235). May function as link between endosomal transport vesicles and dynactin (Probable). Plays a role in the internalization of EGFR after EGF stimulation (Probable). Involved in EGFR endosomal sorting and degradation; the function involves PIP5K1C isoform 3 and is retromer-independent (PubMed:23602387). Together with PIP5K1C isoform 3 facilitates HGS interaction with ubiquitinated EGFR, which initiates EGFR sorting to intraluminal vesicles (ILVs) of the multivesicular body for subsequent lysosomal degradation (Probable). Involved in E-cadherin sorting and degradation; inhibits PIP5K1C isoform 3-mediated E-cadherin degradation (PubMed:24610942). Plays a role in macrop (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. 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.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 40%
Model score: 70
MODL_I-TASSER-3.0

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The reference OMIM entry for this protein is 605937

Sorting nexin 5; snx5

DESCRIPTION

SNX5 is a member of the sorting nexin family of molecules that contain an approximately 100-amino acid region termed the phox homology (PX) domain (Otsuki et al., 1999).

CLONING

Using a yeast 2-hybrid screen with a fragment of FANCA (607139) as bait, Otsuki et al. (1999) identified SNX5 as a putative FANCA-binding protein. Northern blot analysis detected 2 SNX5 transcripts of 2.2 and 1.6 kb, which were present in varying amounts among the tissues and cell lines tested. The highest levels were found in skeletal muscle and kidney as well as in a T-cell leukemia, a colon adenocarcinoma, and a lung carcinoma cell line, and the lowest levels were found in brain, placenta, lung, and liver.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the SNX5 gene to chromosome 20 (TMAP stSG9992).

GENE FUNCTION

Otsuki et al. (1999) confirmed the interaction between FANCA and SNX5 by immunoprecipitation studies. Deletion mutant analysis indicated that the PX domain is not required for binding to FANCA, but that a central region of SNX5 is essential. Otsuki et al. (1999) found that overexpression of SNX5 increased FANCA protein levels, leading them to suggest that FANCA may affect SNX5 traffic with cell surface receptors. 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 (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. ... More on the omim web site

Subscribe to this protein entry history

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 605937 was added.

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed