Syntaxin
Encyclopedia
Syntaxins are a family of membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

 integrated Q-SNARE proteins participating in exocytosis
Exocytosis
Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...

.

Domains

Syntaxins possess a single C-terminal transmembrane domain, a SNARE domain (known as H3), and an N-terminal regulatory domain (Habc).
Syntaxin 17 may have two transmembrane domains.
  • The SNARE (H3) domain binds to both synaptobrevin
    Synaptobrevin
    Synaptobrevins are small integral membrane proteins of secretory vesicles with molecular weight of 18 kilodalton that are part of the vesicle-associated membrane protein family....

     and SNAP-25
    SNAP-25
    Synaptosomal-associated protein 25 is a protein that in humans is encoded by the SNAP25 gene. The SNAP-25 protein is a component of the SNARE complex, which is proposed to account for the specificity of membrane fusion and to directly execute fusion by forming a tight complex that brings the...

     forming the core SNARE complex. Formation of this incredibly stable SNARE core complex is believed to generate the free energy required to initiate fusion between the vesicle membrane and plasma membrane.
  • The N-terminal Habc domain is formed by 3 -helices and when collapsed onto its own H3 helix forms an inactive "closed" syntaxin conformation. This closed conformation of syntaxin is believed to be stabilized by binding of Munc-18
    Munc-18
    Munc-18 protein is the mammalian homologue of the unc-18 protein and is a member of the Sec1/Munc18-like protein family...

     (nSec1), although more recent data suggests that nSec1 may bind to other conformations of syntaxin, as well. The "open" syntaxin conformation is the conformation that is competent to form into SNARE core complexes.

Function

In vitro syntaxin per se is sufficient to drive spontaneous calcium independent fusion of synaptic vesicles containing v-SNAREs.

More recent and somewhat controversial amperometric data suggest that the transmembrane domain of Syntaxin1A may form part of the fusion pore of exocytosis.

Binding

Syntaxins bind synaptotagmin
Synaptotagmin
Synaptotagmins constitute a family of membrane-trafficking proteins that are characterized by an N-terminal transmembrane region , a variable linker, and two C-terminal C2 domains - C2A and C2B. There are 15 members in the mammalian synaptotagmin family...

 in a calcium-dependent fashion and interact with voltage dependent calcium and potassium channels via the C-terminal H3 domain. Direct syntaxin-channel interaction is a suitable molecular mechanism for proximity between the fusion machinery and the gates of entry during depolarization of the presynaptic axonal boutons
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...

.

The Sec1/Munc18 protein family is known to bind to Syntaxin and regulate Syntaxins machinery. Munc18-1 binds to Syntaxin 1A via two distinct sites referred as N-terminus binding and "closed" conformation that incorporates both the central Habc domain and the SNARE core domain. Binding to N-terminus of Syntaxin-1 is thought to facilitate Syntaxin-1 interact with another SNARE. and Binding to "closed" conformation Syntaxin-1 is believed to be inhibitory regulate Syntaxin-1's function.

Recently published data show that alternative spliced Syntaxin 1 (STX1B) which lacks the transmembrane domain localizes in the nuclei.

Genes

Human genes encoding syntaxin proteins include:
  • STX1A
    STX1A
    Syntaxin-1A is a protein that in humans is encoded by the STX1A gene.- Function :Synaptic vesicles store neurotransmitters that are released during calcium-regulated exocytosis. The specificity of neurotransmitter release requires the localization of both synaptic vesicles and calcium channels to...

    , STX1B
    STX1B
    Syntaxin-1B is a protein that in humans is encoded by the STX1B gene.-Further reading:...

    , STX2
    STX2
    Syntaxin-2 is a protein that in humans is encoded by the STX2 gene.-Interactions:STX2 has been shown to interact with SNAP-25, SNAP23, STXBP1 and Syntaxin binding protein 3.-Further reading:...

    , STX3, STX4
    STX4
    Syntaxin-4 is a protein that in humans is encoded by the STX4 gene.-Interactions:STX4 has been shown to interact with SNAP-25, NAPA, STXBP5, SNAP23, Vesicle-associated membrane protein 8, RAB4A, TXLNB, VAMP2, VAMP3, STXBP1 and Syntaxin binding protein 3.-Further reading:...

    , STX5
    STX5
    Syntaxin-5 is a protein that in humans is encoded by the STX5 gene.-Interactions:STX5 has been shown to interact with NAPA, GOSR1, GOSR2, BET1L and USO1.-Further reading:...

    , STX6
    STX6
    Syntaxin-6 is a protein that in humans is encoded by the STX6 gene.-Interactions:STX6 has been shown to interact with SNAP23, VAMP3 and VAMP4.-Further reading:...

    , STX7
    STX7
    Syntaxin-7 is a protein that in humans is encoded by the STX7 gene.In melanocytic cells STX7 gene expression may be regulated by MITF.-Interactions:STX7 has been shown to interact with STX8, VPS18, Vesicle-associated membrane protein 8 and VPS11....

    , STX8
    STX8
    Syntaxin-8 is a protein that in humans is encoded by the STX8 gene.Syntaxin 8 directly interacts with HECTd3 and has similar subcellular localization. The protein has been shown to form the SNARE complex with syntaxin 7, vti1b and endobrevin...

    , STX10
    STX10
    Syntaxin-10 is a SNARE protein that is encoded by the STX10 gene. This protein is found in most vertebrates but is noticeably absent from mice. As with other SNARE proteins, STX10 facilitates vesicle fusion and thus is important for intracellular trafficking of proteins and other cellular...

    , STX11
    STX11
    Syntaxin 11, also known as STX11, is a human gene that is a member of the t-SNARE family.-Interactions:STX11 has been shown to interact with SNAP-25 and SNAP23.-See also:* Hemophagocytic lymphohistiocytosis-Further reading:...

    , STX12
    STX12
    Syntaxin-12 is a protein that in humans is encoded by the STX12 gene.-Further reading:...

    , STX16
    STX16
    Syntaxin-16 is a protein that in humans is encoded by the STX16 gene.It has been associated with pseudohypoparathyroidism type Ib.-Further reading:...

    , STX17, STX18, STX19
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