Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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SynN Syntaxin N-terminal domain

SMART accession number:	SM00503
Description:	Three-helix domain that (in Sso1p) slows the rate of its reaction with the SNAP-25 homologue Sec9p
Interpro abstract (IPR006011):	Syntaxins A and B are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. Syntaxins are a family of receptors for intracellular transport vesicles. Each target membrane may be identified by a specific member of the syntaxin family [(PUBMED:7690687)]. Members of the syntaxin family [(PUBMED:8493722), (PUBMED:8490959)] have a size ranging from 30 Kd to 40 Kd; a C-terminal extremity which is highly hydrophobic and anchors the protein on the cytoplasmic surface of cellular membranes; a central, well conserved region, which seems to be in a coiled-coil conformation.
GO component:	membrane (GO:0016020)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 534 SynN domains in 534 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a SynN domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with SynN domain is also avaliable.

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  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• Literature (relevant references for this domain)

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

  • 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
  • Display abstract

  • 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
  • Display abstract

  • 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.

  • 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
  • Display abstract

  • 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
  • Display abstract

  • 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.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• % proteins involved KEGG pathway ID Description 92.78 map04130 SNARE interactions in vesicular transport 7.22 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 SynN domain which could be assigned to a KEGG orthologous group, and not all proteins containing SynN 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 SynN domains in PDB

  PDB code	Main view	Title
  1br0		Three dimensional structure of the n-terminal domain of syntaxin 1a
  1ez3		Crystal structure of the neuronal t-snare syntaxin-1a
  1fio		Crystal structure of yeast t-snare protein sso1
  1s94		Crystal structure of the habc domain of neuronal syntaxin from the squid loligo pealei
  2dnx		Solution structure of rsgi ruh-063, an n-terminal domain of syntaxin 12 from human cdna
  3c98		Revised structure of the munc18a-syntaxin1 complex

• Links (links to other resources describing this domain)

• INTERPRO	IPR006011

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