Syntaxin-16 (STX16) is a part of a protein family group called SNARE proteins (soluble N-ethylmaleimide-sensitive factor attachment proteins). SNARE proteins can generally be classified into two types: v-SNAREs(vesicle-SNAREs), which are embedded in the membranes of transport vesicles as they form, and t-SNAREs (target-SNAREs), which are located on the target membranes, such as those found at nerve terminals.[5] STX16 is considered to be a t-SNARE, making it a key protein that makes membrane fusion happen.[6]
Gene
Homo Sapiens (Humans)
Syntaxin-16 is a protein that in humans encoded by the STX16gene.[7][8][9][10], it found in Chromosome-20 (Chr 20: 58.65 – 58.68 Mb). It's composed of 325 amino acids[11] . The STX16 gene can be expressed in many different isoforms; It has 23 different splice variants. It also has a lot of evolutionary relatives, including 197 orthologs across species, indicating strong evolutionary conservation. Additionally, it has 12 paralogs within the same genome, and it is related to 2 different phenotypes.[12]
Mus musculus (Mice)
Predicted structure for STX16. Made by AlphaFold, using sequences provided from UniProt to make the predicted structure.
STX16 is found in Chromosome 2 (Chr 2: 173.92 – 173.94 Mb)and encodes a protein that is 326 amino acids long.[13] The STX16 gene can be expressed in many different isoforms; it has 5 different splice variants. It also has many related versions in other species, 197 orthologs across species, indicating strong evolutionary conservation. Additionally, it has 12 paralogs within the genome, and it is related to 29 different phenotypes.[14]
Associations
Homo Sapiens (Humans)
1.It has been associated with pseudohypoparathyroidism type 1B. Losing this gene causes loss of methylation at GNAS1 exon A/B.[9]
Studies have shown that deletions affecting STX16 (syntaxin-16) are linked to Pseudohypoparathyroidism type Ib (PHP-1B). In particular, a “microdeletion” in the STX16 region, either a ~3-kilobase or a novel ~4.4-kilobase deletion which are found in many families with the autosomaldominant form of PHP-1B. People inheriting the deletion from their mother show a loss of DNA methylation specifically at GNAS (guanine nucleotide-binding protein, alpha stimulating) exon A/B, while other differentially methylated regions of GNAS remain unaffected.[9] The loss of this methylation imprint is believed to disrupt the normal regulation of GNAS, particularly by reducing expression of the G protein α-subunit (Gsα) in hormone-responsive tissues such as the kidney, which in turn leads to the PTH (parathyroid hormone) resistance characteristic of PHP-1B.[15]
In short, the deletion of STX16 disrupts a putative “imprinting control element” needed for correct GNAS methylation, and loss of methylation at exon A/B is the molecular hallmark linking STX16 deletions to PHP-1B.[9]
Human - X-ray of TBC1D23 PH domain complexed with STX16. The orange section being STX16 and the green being TBC1D23
2. STX16 has been shown to interact with TBC1D23.[16]
Researchers were able to identify binding partners for the C-terminal “PH-Like” domain of TBC1D23 by using Affinity chromatography and Mass Spectrometry, by doing so they discovered that the cytoplasmic tail of STX16 is able to interact with TBC1D23. It was identified that fragments of STX16 ~151-225 amino acids are both necessary and sufficient for them to interact, establishing a direct binding between TBC1D23 and STX16.
To comprehend their binding, researchers created a 3D structure of the end of TBC1D23 bound to a small piece of STX16. They found that this short segment of STX16 fits tightly along the surface of TBC1D23, slotting two of its amino acids into small pockets and forming additional charge based interactions. This close fit explains why the two proteins are able to specifically recognize each other.
Overall this interconnection between proteins displayed an important role in how cells transport materials. When researchers modified the binding parts of with TBC1D23 or STX16, vesicles were no longer able to properly be captured and directed to the golgi. This outcome indicated that TBC1D23 is acting like a “tether,” that helps the golgi catch incoming vesicles by attaching to STX16 in order to secure cargo being delivered to and from the right place before membrane fusion occurs [16]
↑"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑Wang T, Li L, Hong W (December 2017). "SNARE proteins in membrane trafficking". Traffic. 18 (12): 767–775. doi:10.1111/tra.12524. PMID28857378.
↑Chen Y, Gan BQ, Tang BL (November 2010). "Syntaxin 16: unraveling cellular physiology through a ubiquitous SNARE molecule". Journal of Cellular Physiology. 225 (2): 326–332. doi:10.1002/jcp.22286. PMID20589833.
↑Tang BL, Low DY, Lee SS, Tan AE, Hong W (January 1998). "Molecular cloning and localization of human syntaxin 16, a member of the syntaxin family of SNARE proteins". Biochemical and Biophysical Research Communications. 242 (3): 673–679. Bibcode:1998BBRC..242..673T. doi:10.1006/bbrc.1997.8029. PMID9464276.
↑Simonsen A, Bremnes B, Rønning E, Aasland R, Stenmark H (March 1998). "Syntaxin-16, a putative Golgi t-SNARE". European Journal of Cell Biology. 75 (3): 223–231. doi:10.1016/S0171-9335(98)80116-7. PMID9587053.
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