The domain within your query sequence starts at position 187 and ends at position 254; the E-value for the t_SNARE domain shown below is 1.74e-19.

ITRQALNEIESRHKDIMKLETSIRELHEMFMDMAMFVETQGEMVNNIERNVVNSVDYVEH
AKEETKKA

t_SNARE

Helical region found in SNAREs

• SMART accession number: SM00397
• Description: All alpha-helical motifs that form twisted and parallel four-helix bundles in target soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptor proteins. This motif found in "Q-SNAREs".
• Interpro abstract (IPR000727):

  The process of vesicular fusion with target membranes depends on a set of SNAREs (SNAP-Receptors), which are associated with the fusing membranes [ (PUBMED:9239749) (PUBMED:9232812) ]. Target SNAREs (t-SNAREs) are localised on the target membrane and belong to two different families, the syntaxin-like family and the SNAP-25 like family. One member of each family, together with a v-SNARE localised on the vesicular membrane, are required for fusion.

  The N- and C-terminal coiled-coil domains of members of the SNAP-25 family and the most C-terminal coiled-coil domain of the syntaxin family are related to each other and form a new homology domain of approximately 60 amino acids. This domain is also found in other known proteins involved in vesicular membrane traffic, some of which belong to different protein families [ (PUBMED:9096343) ].

There are 21255 t_SNARE domains in 18689 proteins in SMART's nrdb database.

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Balciunas D, Ronne H
• Evidence of domain swapping within the jumonji family of transcription factors.
• Trends Biochem Sci. 2000; 25: 274-6

• Parlati F, Weber T, McNew JA, Westermann B, Sollner TH, Rothman JE
• Rapid and efficient fusion of phospholipid vesicles by the alpha-helical core of a SNARE complex in the absence of an N-terminal regulatory domain.
• Proc Natl Acad Sci U S A. 1999; 96: 12565-70

A protease-resistant core domain of the neuronal SNARE complex consists of an alpha-helical bundle similar to the proposed fusogenic core of viral fusion proteins [Skehel, J. J. & Wiley, D. C. (1998) Cell 95, 871-874]. We find that the isolated core of a SNARE complex efficiently fuses artificial bilayers and does so faster than full length SNAREs. Unexpectedly, a dramatic increase in speed results from removal of the N-terminal domain of the t-SNARE syntaxin, which does not affect the rate of assembly of v-t SNARES. In the absence of this negative regulatory domain, the half-time for fusion of an entire population of lipid vesicles by isolated SNARE cores ( approximately 10 min) is compatible with the kinetics of fusion in many cell types.

• Edwardson JM
• Membrane fusion: all done with SNAREpins?
• Curr Biol. 1998; 8: 3903-3903

SNARE proteins are sufficient to fuse artificial membranes together. In the cell, vesicle transport may rely on fusion mediated by interaction between vesicle (v) and target (t) SNAREs, whereas the homotypic fusion of organelle biogenesis may be mediated by t-SNARE-t-SNARE interaction.

• Fasshauer D, Sutton RB, Brunger AT, Jahn R
• Conserved structural features of the synaptic fusion complex: SNARE proteins reclassified as Q- and R-SNAREs.
• Proc Natl Acad Sci U S A. 1998; 95: 15781-6

SNARE [soluble NSF (N-ethylmaleimide-sensitive fusion protein) attachment protein receptor] proteins are essential for membrane fusion and are conserved from yeast to humans. Sequence alignments of the most conserved regions were mapped onto the recently solved crystal structure of the heterotrimeric synaptic fusion complex. The association of the four alpha-helices in the synaptic fusion complex structure produces highly conserved layers of interacting amino acid side chains in the center of the four-helix bundle. Mutations in these layers reduce complex stability and cause defects in membrane traffic even in distantly related SNAREs. When syntaxin-4 is modeled into the synaptic fusion complex as a replacement of syntaxin-1A, no major steric clashes arise and the most variable amino acids localize to the outer surface of the complex. We conclude that the main structural features of the neuronal complex are highly conserved during evolution. On the basis of these features we have reclassified SNARE proteins into Q-SNAREs and R-SNAREs, and we propose that fusion-competent SNARE complexes generally consist of four-helix bundles composed of three Q-SNAREs and one R-SNARE.

• Fernandez I, Ubach J, Dulubova I, Zhang X, Sudhof TC, Rizo J
• Three-dimensional structure of an evolutionarily conserved N-terminal domain of syntaxin 1A.
• Cell. 1998; 94: 841-9

Syntaxin 1A plays a central role in neurotransmitter release through multiple protein-protein interactions. We have used NMR spectroscopy to identify an autonomously folded N-terminal domain in syntaxin 1A and to elucidate its three-dimensional structure. This 120-residue N-terminal domain is conserved in plasma membrane syntaxins but not in other syntaxins, indicating a specific role in exocytosis. The domain contains three long alpha helices that form an up-and-down bundle with a left-handed twist. A striking residue conservation is observed throughout a long groove that is likely to provide a specific surface for protein-protein interactions. A highly acidic region binds to the C2A domain of synaptotagmin I in a Ca2+-dependent interaction that may serve as an electrostatic switch in neurotransmitter release.

• Nicholson KL, Munson M, Miller RB, Filip TJ, Fairman R, Hughson FM
• Regulation of SNARE complex assembly by an N-terminal domain of the t-SNARE Sso1p.
• Nat Struct Biol. 1998; 5: 793-802

The fusion of intracellular transport vesicles with their target membranes requires the assembly of SNARE proteins anchored in the apposed membranes. Here we use recombinant cytoplasmic domains of the yeast SNAREs involved in Golgi to plasma membrane trafficking to examine this assembly process in vitro. Binary complexes form between the target membrane SNAREs Sso1p and Sec9p; these binary complexes can subsequently bind to the vesicle SNARE Snc2p to form ternary complexes. Binary and ternary complex assembly are accompanied by large increases in alpha-helical structure, indicating that folding and complex formation are linked. Surprisingly, we find that binary complex formation is extremely slow, with a second-order rate constant of approximately 3 M(-1) s(-1). An N-terminal regulatory domain of Sso1p accounts for slow assembly, since in its absence complexes assemble 2,000-fold more rapidly. Once binary complexes form, ternary complex formation is rapid and is not affected by the presence of the regulatory domain. Our results imply that proteins that accelerate SNARE assembly in vivo act by relieving inhibition by this regulatory domain.

• Poirier MA, Xiao W, Macosko JC, Chan C, Shin YK, Bennett MK
• The synaptic SNARE complex is a parallel four-stranded helical bundle.
• Nat Struct Biol. 1998; 5: 765-9

The heterotrimeric synaptic soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, consisting of the synaptic vesicle-associated membrane protein 2 (VAMP2) and presynaptic plasma membrane proteins SNAP-25 (synaptosome-associated protein of 25,000 Mr) and syntaxin 1A, is a critical component of the exocytotic machinery. We have used spin labeling electron paramagnetic resonance spectroscopy to investigate the structural organization of this complex, particularly the two predicted helical domains contributed by SNAP-25. Our results indicate that the N- and C-terminal domains of SNAP-25 are parallel to each other and to the C-terminal domain of syntaxin 1A. Based on these findings, we propose a parallel four-stranded coiled coil model for the structure of the synaptic SNARE complex.

• Sutton RB, Fasshauer D, Jahn R, Brunger AT
• Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution.
• Nature. 1998; 395: 347-53

The evolutionarily conserved SNARE proteins and their complexes are involved in the fusion of vesicles with their target membranes; however, the overall organization and structural details of these complexes are unknown. Here we report the X-ray crystal structure at 2.4 A resolution of a core synaptic fusion complex containing syntaxin-1 A, synaptobrevin-II and SNAP-25B. The structure reveals a highly twisted and parallel four-helix bundle that differs from the bundles described for the haemagglutinin and HIV/SIV gp41 membrane-fusion proteins. Conserved leucine-zipper-like layers are found at the centre of the synaptic fusion complex. Embedded within these leucine-zipper layers is an ionic layer consisting of an arginine and three glutamine residues contributed from each of the four alpha-helices. These residues are highly conserved across the entire SNARE family. The regions flanking the leucine-zipper-like layers contain a hydrophobic core similar to that of more general four-helix-bundle proteins. The surface of the synaptic fusion complex is highly grooved and possesses distinct hydrophilic, hydrophobic and charged regions. These characteristics may be important for membrane fusion and for the binding of regulatory factors affecting neurotransmission.

• Weimbs T, Mostov K, Low SH, Hofmann K
• A model for structural similarity between different SNARE complexes based on sequence relationships.
• Trends Cell Biol. 1998; 8: 260-2

• Fedorov AA, Lappalainen P, Fedorov EV, Drubin DG, Almo SC
• Structure determination of yeast cofilin.
• Nat Struct Biol. 1997; 4: 366-9

Cofilin, a ubiquitous 15,000 M(r) protein, plays a central role in regulating cytoskeletal dynamics. Cofilin binds to actin monomers and filaments, and has a pH-dependent actin severing activity. The structure will allow for a detailed analysis of cofilin function.

• Weimbs T, Low SH, Chapin SJ, Mostov KE, Bucher P, Hofmann K
• A conserved domain is present in different families of vesicular fusion proteins: a new superfamily.
• Proc Natl Acad Sci U S A. 1997; 94: 3046-51

We have analyzed conserved domains in t-SNAREs [soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors in the target membrane], proteins that are believed to be involved in the fusion of transport vesicles with their target membrane. By using a sensitive computer method, the generalized profile method, we were able to identify a new homology domain that is common in the two protein families previously identified to act as t-SNAREs, the syntaxin and SNAP-25 (synaptosome-associated protein of 25 kDa) families, which therefore constitute a new superfamily. This homology domain of approximately 60 amino acids is predicted to form a coiled-coil structure. The significance of this homology domain could be demonstrated by a partial suppression of the coiled-coil properties of the domain profile. In proteins belonging to the syntaxin family, a single homology domain is located near the transmembrane domain, whereas the members of the SNAP-25 family possess two homology domains. This domain was also identified in several proteins that have been implicated in vesicular transport but do not belong to any of the t-SNARE protein families. Several new yeast, nematode, and mammalian proteins were identified that belong to the new superfamily. The evolutionary conservation of the SNARE coiled-coil homology domain suggests that this domain has a similar function in different membrane fusion proteins.

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
97.54	map04130	SNARE interactions in vesicular transport
2.46	map05020	Parkinson's disease

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with t_SNARE domain which could be assigned to a KEGG orthologous group, and not all proteins containing t_SNARE domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of t_SNARE domains in PDB

PDB code	Title
1gl2	crystal structure of an endosomal SNARE core complex
1hvv	SELF-ASSOCIATION OF THE H3 REGION OF SYNTAXIN 1A: IMPLICATIONS FOR SNARE COMPLEX ASSEMBLY
1jth	Crystal structure and biophysical properties of a complex between the N-terminal region of SNAP25 and the SNARE region of syntaxin 1a
1kil	Three-dimensional structure of the complexin/SNARE complex
1l4a	X-RAY STRUCTURE OF THE NEURONAL COMPLEXIN/SNARE COMPLEX FROM THE SQUID LOLIGO PEALEI
1n7s	High Resolution Structure of a Truncated Neuronal SNARE Complex
1sfc	NEURONAL SYNAPTIC FUSION COMPLEX
1urq	Crystal structure of neuronal Q-SNAREs in complex with R-SNARE motif of Tomosyn
1xtg	Crystal structure of NEUROTOXIN BONT/A complexed with Synaptosomal-associated protein 25
2m8r	Pre-Fusion Solution NMR Structure of Neuronal SNARE Syntaxin 1A
2n1t	2N1T
2nps	Crystal Structure of the Early Endosomal SNARE Complex
2xhe	Crystal structure of the Unc18-syntaxin 1 complex from Monosiga brevicollis
3b5n	Structure of the yeast plasma membrane SNARE complex
3c98	Revised structure of the munc18a-syntaxin1 complex
3hd7	HELICAL EXTENSION OF THE NEURONAL SNARE COMPLEX INTO THE MEMBRANE, spacegroup C 1 2 1
3ipd	Helical extension of the neuronal SNARE complex into the membrane, spacegroup I 21 21 21
3j96	3J96
3j97	3J97
3j98	3J98
3j99	3J99
3rk2	Truncated SNARE complex
3rk3	Truncated SNARE complex with complexin
3rl0	Truncated SNARE complex with complexin (P1)
3zur	Crystal structure of an engineered botulinum neurotoxin type A- SNARE23 derivative, LC0-A-SNAP25-Hn-A
3zus	Crystal structure of an engineered botulinum neurotoxin type A- SNARE23 derivative, LC-A-SNAP23-Hn-A
4jeh	Crystal Structure of Munc18a and Syntaxin1 lacking N-peptide complex
4jeu	Crystal Structure of Munc18a and Syntaxin1 with native N-terminus complex
4wy4	4WY4
5buz	5BUZ
5ccg	5CCG
5cch	5CCH
5cci	5CCI
5kj7	5KJ7
5kj8	5KJ8

Links (links to other resources describing this domain)

• INTERPRO: IPR000727