Syntaxin-4 (STX4)

The protein contains 297 amino acids for an estimated molecular weight of 34180 Da.

 

Plasma membrane t-SNARE that mediates docking of transport vesicles. Necessary for the translocation of SLC2A4 from intracellular vesicles to the plasma membrane. Together with STXB3 and VAMP2, may also play a role in docking/fusion of intracellular GLUT4-containing vesicles with the cell surface in adipocytes (By similarity). May also play a role in docking of synaptic vesicles at presynaptic active zones. (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. 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.

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.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 99%
Model score: 0
No model available.

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The reference OMIM entry for this protein is 186591

Syntaxin 4; stx4
Stx4a
Syntaxin, placental
P35-2

CLONING

Li et al. (1994) described the nucleotide sequence of STX4A, a syntaxin gene isolated from a placenta library. (The gene was previously symbolized STX2.) It encodes a predicted 297-amino acid protein that is 89% identical to the amino acid sequence of rat Stx4a. By immunohistochemical analysis of rat brain sections, Kennedy et al. (2010) showed that Stx4 was expressed throughout brain. In rat hippocampal neurons, Stx4 showed a punctate distribution in the somatodendritic compartment, and Stx4 clusters often localized to dendritic spines. Immunogold electron microscopy of CA1 rat hippocampus revealed frequent Stx4 labeling near spine membranes at sites lateral to postsynaptic densities, with occasional labeling of presynaptic membranes. Biochemical fractionation of mouse brain revealed Stx4 in synaptosome fractions, but not in synaptic vesicle fractions.

MAPPING

Gross (2014) mapped the STX4 gene to chromosome 16p11.2 based on an alignment of the STX4 sequence (GenBank GENBANK AF026007) with the genomic sequence (GRCh37).

GENE FUNCTION

Mandon et al. (1996) stated that vesicle-associated membrane proteins (VAMPs) or synaptobrevins (see 185880) are proposed to bind to cognate vesicle-targeting receptors in target membranes, which include several members of the syntaxin family. The molecular mechanisms responsible for targeting of vesicles containing aquaporin-2 (AQP2; 107777) to the apical plasma membrane of renal collecting duct cells may involve the vesicle-targeting protein STX4. Among the known syntaxin isoforms, only STX1 (STX1A; 186590) and STX4 bind VAMP2 (185881) with high affinity. Thus, STX1 and STX4 could be considered candidates for a role in targeting of the AQP2/VAMP2-containing vesicles to the apical plasma membrane in collecting duct cells. In contrast to STX1, which is expressed predominantly in the central nervous system, STX4 is expressed in a variety of tissues including the kidney. Mandon et al. (1996) used sequence data for rat Stx1a, Stx1b (601485), and Stx4 from Bennett et al. (1993) to design PCR primers for RT-PCR analysis of rat tissues. They detected Stx4 mRNA in the apical plasma membrane of collecting duct principal cells. They also demonstrated in the rat kidney the presence of a protein with the characteristics of Stx4 in the apical plasma membrane of inner medullary-collecting duct cells. To clarify the physiologic function of STXBP3 (608339) in insulin-stimulated GLUT4 (SLC2A4; 138190) exocytosis, Kanda et al. (2005) generated mouse embryos deficient in the Stx4-binding protein Stxbp3 and developed Stxbp3 -/- adipocytes from their mesenchymal fibroblasts. The insulin-induced appearance of Glut4 at the cell surface was enhanced in Stxbp3 -/- adipocytes compared to +/+ cells. Wortmannin, an inhibitor of PI3K, inhibited insulin-stimulated Glut4 externalization in +/+ but not -/- adipocytes. Kanda et al. (2005) suggested that disruption of the interaction between STX4 and STXBP3 in adipocytes might result in enhancement of insulin-stimulated GLUT4 externalization. Using RT-PCR, immunoblot analysis, and immunofluorescence microscopy, Sander et al. (2008) demonstrated that human intestinal mast cells (MCs) expressed SNAP23 (602534), STX1B, STX2 (132350), STX3 (STX3A; 600876), STX4, and STX6 (603944), but not SNAP25 (600322). MCs also expressed VAMP3 (603657), VAMP7 (300053), and VAMP8 (603177), but, in contrast with rodent MCs, they expressed only low levels of VAMP2 (1858 ... 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 186591 was added.