STX16

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]

STX16
Identifiers
Aliases	STX16, SYN16, syntaxin 16, SYN-16
External IDs	OMIM: 603666; MGI: 1923396; HomoloGene: 2791; GeneCards: STX16; OMA:STX16 - orthologs
Gene location (Human) Chr. Chromosome 20 (human)[1] Band 20q13.32 Start 58,651,253 bp[1] End 58,679,526 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 H4 Start 173,918,101 bp[2] End 173,941,564 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right uterine tube sural nerve corpus callosum superficial temporal artery pituitary gland right hemisphere of cerebellum body of uterus C1 segment right ovary anterior pituitary Top expressed in hand neural layer of retina otolith organ utricle thymus lens cerebellar cortex primary visual cortex yolk sac superior frontal gyrus More reference expression data BioGPS n/a
Gene ontology Molecular function SNAP receptor activity protein binding syntaxin binding SNARE binding Cellular component cytoplasm integral component of membrane Golgi apparatus membrane intracellular membrane-bounded organelle Golgi cisterna focal adhesion trans-Golgi network SNARE complex endoplasmic reticulum perinuclear region of cytoplasm cytosol trans-Golgi network membrane Golgi membrane endomembrane system integral component of synaptic vesicle membrane Biological process vesicle docking retrograde transport, endosome to Golgi protein transport intracellular protein transport vesicle fusion Golgi ribbon formation vesicle-mediated transport transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8675 228960 Ensembl ENSG00000124222 ENSMUSG00000027522 UniProt O14662 Q8BVI5 RefSeq (mRNA) NM_001001433 NM_001001434 NM_001134772 NM_001134773 NM_001204868 NM_003763 NM_001102423 NM_001102424 NM_001102425 NM_172675 NM_001363029 NM_001363030 NM_001363031 RefSeq (protein) NP_001001433 NP_001128244 NP_001128245 NP_001191797 NP_003754 NP_001095893 NP_001095894 NP_001095895 NP_766263 NP_001349958 NP_001349959 NP_001349960 Location (UCSC) Chr 20: 58.65 – 58.68 Mb Chr 2: 173.92 – 173.94 Mb PubMed search [3] [4]
Wikidata
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Gene

Homo Sapiens (Humans)

Syntaxin-16 is a protein that in humans encoded by the STX16 gene.^{[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 autosomal dominant 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]

Mus musculus (Mice)  

This protein is thought to participate in multiple cellular processes, such as endosomal trafficking, vesicle docking, and vesicle fusion. It is localized to the Golgi apparatus and is expressed in a variety of tissues, including the central nervous system, connective tissue, the genitourinary system, the gut, and the immune system. ^[17]

STX16 Molecular Functions^[18]

• Protein binding
• Syntaxin binding
• SNAP receptor activity
• SNARE binding

Cellular locations where the STX16 product is active^[18]

• Golgi membrane
• Golgi apparatus
• trans-Golgi network
• perinuclear region of cytoplasm
• focal adhesion
• cytoplasm
• intracellular membrane-bounded organelle
• SNARE complex
• cytosol
• endomembrane system
• synaptic vesicle membrane
• Golgi cisterna
• trans-Golgi network membrane