Syntaxin-6 (STX6)

The protein contains 255 amino acids for an estimated molecular weight of 29176 Da.

 

Involved in intracellular vesicle trafficking. (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. 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. 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.
  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.
  6. 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 predicted to be membranous by TOPCONS.

Topcons

Interpro domains
Total structural coverage: 43%
Model score: 40
MODL_I-TASSER-3.0
MODL_I-TASSER-3.0

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The reference OMIM entry for this protein is 603944

Syntaxin 6; stx6

DESCRIPTION

STX6 belongs to the Qbc subfamily of SNARE proteins (see 600322) and localizes to the trans-Golgi network (TGN) and endosomes. It has a role in sorting proteins from endosomes toward either the TGN or lysosomes (summary by Cheng et al., 2010).

CLONING

By RT-PCR with primers based on the sequence of rat syntaxin-6, Martin-Martin et al. (1999) isolated a human syntaxin-6 cDNA.

GENE FUNCTION

Exocytosis of various types of cytoplasmic granules present in human neutrophils plays a critical role in neutrophil biology and appears to regulate a number of neutrophil functions in both inflammation and infection. To elucidate the mechanisms that regulate neutrophil exocytosis, Martin-Martin et al. (1999) studied the expression of syntaxins, cellular receptors for transport vesicles (see 603765), in neutrophils. By RT-PCR, they found that neutrophils and peripheral blood lymphocytes express numerous syntaxins, including syntaxin-1A (186590), -3 (600876), and -6. The expression of several syntaxin genes increased during dimethyl sulfoxide-induced differentiation of a human promyelocytic leukemia cell line toward the neutrophil lineage. By immunolocalization analysis, Advani et al. (1998) found that STX6 partially colocalizes with VAMP4 (606909) in a punctate juxtanuclear staining pattern. By immunoprecipitation of rat brain detergent extracts, Steegmaier et al. (1999) found that STX6 exists in a complex with VAMP4. Western blot analysis and immunofluorescence microscopy by Charest et al. (2001) showed that FIG (GOPC; 606845) interacted through its C-terminal coiled-coil domain with syntaxin-6 in the Golgi apparatus. They proposed that FIG may be involved in membrane vesicle trafficking. Cheng et al. (2010) showed that both STX6 and CAL (GOPC) were involved in downregulation of CFTR (602421) via lysosome-mediated degradation. STX6 bound the N terminus of CFTR, and CAL independently bound the C terminus of CFTR. Overexpression of STX6 reduced cell surface expression of CFTR and caused its instability, but not in the absence of CAL. STX6-dependent CFTR instability was sensitive to lysosome inhibition. Overexpression of a dominant-negative STX6 mutant or knockdown of STX6 resulted in CFTR stability. STX6 and CAL had no effect on the stability of CFTR with the cystic fibrosis (219700)-associated delta-F508 mutation (602421.0001), which is retained in the endoplasmic reticulum (ER) and undergoes ER-associated degradation. Cheng et al. (2010) concluded that STX6 and CAL function in the TGN and direct trafficking of CFTR to the lysosome.

BIOCHEMICAL FEATURES

Misura et al. (2002) provided a description of the 3-dimensional structure of the amino-terminal domain of syntaxin-6. Secondary structure prediction of SNARE proteins showed that the N-terminal domains of many syntaxin and SNAP25 (600322) family members are likely to be similar to one another, but are distinct from those of the VAMP family members (see VAMP1, 185880), indicating that syntaxin and SNAP25 SNAREs may have shared a common ancestor. ... 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 603944 was added.

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed