Sorting nexin-2 (SNX2)

The protein contains 519 amino acids for an estimated molecular weight of 58471 Da.

 

Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (PubMed:16179610). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex (PubMed:17101778). 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). Can sense membrane curvature and has in vitro vesicle-to-membrane remodeling activity (PubMed:23085988). Required for retrograde endosome-to-TGN transport of TGN38 (PubMed:20138391). Promotes KALRN- and RHOG-dependent but retromer-independent membrane remodeling such as lamellipodium formation; the function is dependent on GEF activity of KALRN (PubMed:20604901). (updated: April 1, 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. 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.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

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)

Interpro domains
Total structural coverage: 55%
Model score: 0
No model available.

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The reference OMIM entry for this protein is 605929

Sorting nexin 2; snx2

DESCRIPTION

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).

CLONING

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.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the SNX2 gene to chromosome 5q23 (TMAP stSG21976).

GENE FUNCTION

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. ... 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 605929 was added.