Sorting nexin-9 (SNX9)

The protein contains 595 amino acids for an estimated molecular weight of 66592 Da.

 

Involved in endocytosis and intracellular vesicle trafficking, both during interphase and at the end of mitosis. Required for efficient progress through mitosis and cytokinesis. Required for normal formation of the cleavage furrow at the end of mitosis. Plays a role in endocytosis via clathrin-coated pits, but also clathrin-independent, actin-dependent fluid-phase endocytosis. Plays a role in macropinocytosis. Promotes internalization of TNFR. Promotes degradation of EGFR after EGF signaling. Stimulates the GTPase activity of DNM1. Promotes DNM1 oligomerization. Promotes activation of the Arp2/3 complex by WASL, and thereby plays a role in the reorganization of the F-actin cytoskeleton. Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate and promotes membrane tubulation. Has lower affinity for membranes enriched in phosphatidylinositol 3-phosphate. (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. 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.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. 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)

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 66%
Model score: 32
MODL_I-TASSER-3.0

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The reference OMIM entry for this protein is 605952

Sorting nexin 9; snx9
Sh3 domain- and px domain-containing protein; sh3px1

DESCRIPTION

Members of the sorting nexin protein family, such as SNX9, contain a phospholipid-binding module called the phox homology (PX) domain. SNX9 functions in clathrin (see 118955)-mediated endocytosis and clathrin-independent, actin (see 102610)-dependent fluid-phase endocytosis (Yarar et al., 2007).

CLONING

By use of a yeast 2-hybrid screen, Howard et al. (1999) identified 2 SH3 domain-containing proteins, endophilin-1 (SH3GL2; 604465) and SNX9, that interact with the cytoplasmic domains of metalloprotease disintegrins ADAM9 (602713) and ADAM15 (605548). The 595-amino acid SNX9 protein contains an N-terminal SH3 domain, followed by a PX domain and a C-terminal coiled-coil domain. Northern blot analysis detected wide expression of 4.4- and 3.1-kb transcripts, with high levels in heart and placenta and relatively low levels in thymus and peripheral blood leukocytes.

GENE FUNCTION

Howard et al. (1999) determined that binding of the SH3 domain of SNX9 to ADAM9 and ADAM15 required the C-terminal proline-rich region of the ADAM9 and ADAM15 cytoplasmic tails. Both SNX9 and SH3GL2 preferentially bound the precursors, but not the processed forms, of ADAM9 and ADAM15. Using green monkey kidney cells, Yarar et al. (2007) showed that SNX9 was required for clathrin-independent, actin-dependent fluid-phase endocytosis. SNX9 directly regulated F-actin nucleation through N-WASP (WASL; 605056) and the ARP2 (ACTR2; 604221)/ARP3 (ACTR3; 604222) complex, and this activity was synergistically enhanced by phosphatidylinositol(4,5)bisphosphate-containing liposomes. Yarar et al. (2007) concluded that SNX9 physically couples F-actin nucleation to plasma membrane remodeling during endocytosis. Posor et al. (2013) showed that the BAR domain protein SNX9 is a phosphatidylinositol-3,4-bisphosphate (PI(3,4)P2) effector at clathrin-coated pits in clathrin-mediated endocytosis. Timed formation of PI(3,4)P2 by class 2 phosphatidylinositol-3-kinase C2A (PI3KC2A; 603601) is required for selective enrichment of SNX9 at late-stage endocytic intermediates.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the SNX9 gene to chromosome 6 (TMAP WI-19319). ... 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 605952 was added.

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