Syntaxin 1
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Syntaxins are a family of
membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. Bi ...
integrated
Q-SNARE SNARE proteins – " SNAP REceptors" – are a large protein family consisting of at least 24 members in yeasts and more than 60 members in mammalian and plant cells. The primary role of SNARE proteins is to mediate the fusion of vesicles ...
proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...
participating in
exocytosis Exocytosis is a term for the active transport process that transports large molecules from cell to the extracellular area. Hormones, proteins and neurotransmitters are examples of large molecules that can be transported out of the cell. Exocytosis ...
.


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 Synaptobrevins (''synaptobrevin isotypes 1-2'') are small integral membrane proteins of secretory vesicles with molecular weight of 18 kilodalton (kDa) that are part of the vesicle-associated membrane protein (VAMP) family. Synaptobre ...
and
SNAP-25 Synaptosomal-Associated Protein, 25kDa (SNAP-25) is a Target Soluble NSF (''N''-ethylmaleimide-sensitive factor) Attachment Protein Receptor ( t-SNARE) protein encoded by the ''SNAP25'' gene found on chromosome 20p12.2 in humans. SNAP-25 is a com ...
forming the
core SNARE complex SNARE proteins – " SNAP REceptors" – are a large protein family consisting of at least 24 members in yeasts and more than 60 members in mammalian and plant cells. The primary role of SNARE proteins is to mediate the fusion of vesicles ...
. Formation of this 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 α-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 (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 In a neuron, synaptic vesicles (or neurotransmitter vesicles) store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impul ...
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 Synaptotagmins (SYTs) constitute a family of cell membrane, membrane-trafficking proteins that are characterized by an N-terminal transmembrane region (TMR), a variable linker, and two C-terminal C2 domains - C2A and C2B. There are 17 Protein isof ...
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 Ca2+ entry during depolarization of the presynaptic axonal boutons. 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 The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...
binding and "closed" conformation that incorporates both the central Habc domain and the SNARE core domain. Munc18-1 binding to the N-terminus of Syntaxin-1 is thought to facilitate Syntaxin-1 interaction with another SNARE, while binding to the "closed" conformation of Syntaxin-1 is believed to be inhibitory. 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 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 localiz ...
,
STX1B Syntaxin-1B is a protein that in humans is encoded by the ''STX1B'' gene. Interactions STX1B has been shown to interact with UNC13B Protein unc-13 homolog B is a protein that in humans is encoded by the ''UNC13B'' gene. Function This gen ...
,
STX2 Syntaxin-2, also known as epimorphin, is a protein that in humans is encoded by the ''STX2'' gene. The product of this gene belongs to the syntaxin/epimorphin family of proteins. The syntaxins are a large protein family implicated in the targeti ...
,
STX3 Syntaxin 3, also known as STX3, is a protein which in humans is encoded by the ''STX3'' gene. Function The protein encoded by this gene is a member of the syntaxin family of cellular receptors for transport vesicles which participate in exocyt ...
,
STX4 Syntaxin-4 is a protein that in humans is encoded by the ''STX4'' gene. Interactions STX4 has been shown to Protein-protein interaction, interact with: * Gelsolin, * NAPA (gene), NAPA, * RAB4A, * SNAP-25, * SNAP23, * STXBP1, * STXBP5, ...
,
STX5 Syntaxin-5 is a protein that in humans is encoded by the ''STX5'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to ...
,
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. N terminal protein domain The protein domain Syntaxin 6 N terminal protein domain is a so ...
,
STX7 Syntaxin-7 is a protein that in humans is encoded by the ''STX7'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to ...
,
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 endobrev ...
, *
STX10 Syntaxin-10 (STX10) is a SNARE protein that is encoded by the ''STX10'' gene. This protein is found in most vertebrates (including humans) but is noticeably absent from mice. As with other SNARE proteins, STX10 facilitates vesicle fusion and t ...
,
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 SNAP25 and SNAP23. See also * Hemophagocytic lymphohistiocytosis * Peutz–Jeghers syndrome Peu ...
,
STX12 Syntaxin-12 is a protein that in humans is encoded by the ''STX12'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed ...
,
STX16 Syntaxin-16 is a protein that in humans is encoded by the ''STX16'' gene. It has been associated with pseudohypoparathyroidism type Ib. Losing this gene causes loss of methylation at GNAS1 exon A/B. Interactions STX16 has been shown to inter ...
,
STX17 Syntaxin 17 is a protein that in humans is encoded by the ''STX17'' gene. In horses a duplication in intron 6 causes progressive graying. See also *Syntaxin Syntaxins are a family of membrane integrated Q-SNARE proteins participating in exocy ...
, STX18, STX19


See also

* Tomosyn, a syntaxin binding protein


References


External links

* {{Vesicular transport proteins Single-pass transmembrane proteins