Summary: Synaptobrevin

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Wikipedia: Synaptobrevin
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Synaptobrevin Edit Wikipedia article

Synaptobrevin

Three different views of the high resolution structure of a truncated neuronal SNARE complex. Legend: synaptobrevin-2 (red), Syntaxin-1 (pink), SNAP-25 (purple).

Identifiers

Symbol

Synaptobrevin

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

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.^[1]^[2]^[3]^[4]^[5]

Synaptobrevin is one of the SNARE proteins involved in formation of the SNARE complexes.

Structure

Out of four α-helices of the core SNARE complex one is contributed by synaptobrevin, one by syntaxin, and two by SNAP-25 (in neurons).

Function

SNARE proteins are the key components of the molecular machinery that drives fusion of membranes in exocytosis. Their function however is subject to fine-tuning by various regulatory proteins collectively referred to as SNARE masters.

Classification

In the Q/R nomenclature for organizing SNARE proteins, VAMP/synaptobrevin family members are classified as R-SNAREs, so named for the presence of an arginine at a specific location within the primary sequence of the protein (as opposed to the SNAREs of the target membrane, which contain a glutamine and are so named Q-SNAREs). Synaptobrevin is classified as a V-SNARE in the V/T nomenclature, an alternative classification scheme in which SNAREs are classified as V-SNAREs and T-SNAREs for their localization to vesicles and target membranes, respectively.^[6]

Clinical significance

Synaptobrevin is degraded by tetanospasmin, a protein derived from the bacterium Clostridium tetani, which causes tetanus. A related bacterium, Clostridium botulinum, produces botulinum toxin that also hydrolyzes synaptobrevin.

Human proteins containing this domain

SEC22A; SEC22B; SYBL1; VAMP1; VAMP2; VAMP3; VAMP4; VAMP5; VAMP8; YKT6;

References and notes

^ Baumert M, Maycox PR, Navone F, De Camilli P, Jahn R (February 1, 1989). "Synaptobrevin: an integral membrane protein of 18,000 daltons present in small synaptic vesicles of rat brain". EMBO J. 8 (2): 379–84. PMC 400817. PMID 2498078.
^ Bock JB, Scheller RH (October 1999). "SNARE proteins mediate lipid bilayer fusion". Proc. Natl. Acad. Sci. U.S.A. 96 (22): 12227–9. doi:10.1073/pnas.96.22.12227. PMC 34255. PMID 10535902.
^ Ernst JA, Brunger AT (2003). "High resolution structure, stability, and synaptotagmin binding of a truncated neuronal SNARE complex". J Biol Chem. 278 (10): 8630–6. doi:10.1074/jbc.M211889200. PMID 12496247.
^ Fasshauer D, Sutton RB, Brunger AT, Jahn R (December 1998). "Conserved structural features of the synaptic fusion complex: SNARE proteins reclassified as Q- and R-SNAREs". Proc. Natl. Acad. Sci. U.S.A. 95 (26): 15781–6. doi:10.1073/pnas.95.26.15781. PMC 28121. PMID 9861047.
^ Weber T, Zemelman BV, McNew JA, Westermann B, Gmachl M, Parlati F, Sollner TH, Rothman JE (1998). "SNAREpins: minimal machinery for membrane fusion". Cell. 92 (6): 759–72. doi:10.1016/S0092-8674(00)81404-X. PMID 9529252.
^ Juan S. Bonifacino and Benjamin S. Glick. "The Mechanisms of Vesicle Budding and Fusion." Cell, Vol. 116, 153–166, January 23, 2004,

External links

Synaptobrevin at the US National Library of Medicine Medical Subject Headings (MeSH)

Membrane protein: vesicular transport proteins (TC 1F)

Synaptic vesicle

SNARE

Q-SNARE	SNAP25 SNAP29 Syntaxin STX1A STX1B STX2 STX3 STX4 STX5 STX6 STX7 STX8 STX10 STX11 STX12 STX16 STX17 STX18 STX19 Munc-18: STXBP1 STXBP2 STXBP3 STXBP4 STXBP5 STXBP6

R-SNARE	Synaptobrevin/VAMP: VAMP1 VAMP2 VAMP3

Synaptotagmin

Other

Small GTPase: RAB3A

COPI

Coatomer
- COPA
- COPB1
- COPB2
- COPD/Archain
- COPE
- COPG
- COPG2
- COPZ1
- COPZ2

Small GTPase: ARF

COPII

Coatomer
- SEC23A/SEC24A
- SEC13/SEC31

Small GTPase: SAR1A

RME/Clathrin

Caveolae

Other/ungrouped

Vesicle formation

Adaptor protein complex 1:	AP1AR AP1B1 AP1G1 AP1G2 AP1M1 AP1M2 AP1S1 AP1S2 AP1S3

Adaptor protein complex 2:	AP2A1 AP2A2 AP2B1 AP2M1 AP2S1

Adaptor protein complex 3:	AP3B1 AP3B2 AP3D1 AP3M1 AP3M2 AP3S1 AP3S2

Adaptor protein complex 4:	AP4B1 AP4E1 AP4M1 AP4S1

LMAN1

LYST

BLOC-1:	DTNBP1 BLOC153

BLOC-2:	HPS3 HPS5 HPS6

BLOC-3:	HPS1 HPS4

Coats:	Retromer TIP47

Small GTPase

Dynamin
- DNM1
- DNM2
- DNM3

Other

Sorting nexins

SYNRG

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Synaptobrevin Provide feedback

No Pfam abstract.

Internal database links

SCOOP:

Ferlin_C MCU SNARE

External database links

PROSITE:	PDOC00368
SCOP:	1sfc

This tab holds annotation information from the InterPro database.

InterPro entry IPR001388

Synaptobrevin is an intrinsic membrane protein of small synaptic vesicles [PUBMED:2560644], specialised secretory organelles of neurons that actively accumulate neurotransmitters and participate in their calcium-dependent release by exocytosis. Vesicle function is mediated by proteins in their membranes, although the precise nature of the protein-protein interactions underlying this are still uncertain [PUBMED:1976629]. Synaptobrevin may play a role in the molecular events underlying neurotransmitter release and vesicle recycling and may be involved in the regulation of membrane flow in the nerve terminal, a process mediated by interaction with low molecular weight GTP-binding proteins [PUBMED:8406010]. Synaptic vesicle-associated membrane proteins (VAMPs) from Torpedo californica (Pacific electric ray) and SNC1 from yeast are related to synaptobrevin.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Cellular component	integral component of membrane (GO:0016021)
Biological process	vesicle-mediated transport (GO:0016192)

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan SNARE-fusion (CL0445), which has the following description:

The SNARE-fusion complex families are characterised by being tetrameric coiled-coil structures.

The clan contains the following 3 members:

Synaptobrevin Syntaxin Syntaxin_2

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
UniProt: alignment generated by searching the UniProtKB sequence database using the family HMM
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

Viewing

You can see the alignments as HTML or in three different sequence viewers:

jalview: a Java applet developed at the University of Dundee. You will need Java installed before running jalview
HTML: an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
PP/Heatmap: an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.

Reformatting

You can download (or view in your browser) a text representation of a Pfam alignment in various formats:

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Stockholm
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You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.

Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

	Seed (96)	Full (4914)	Representative proteomes				UniProt (7208)	NCBI (9033)	Meta (37)
	Seed (96)	Full (4914)	RP15 (1290)	RP35 (2677)	RP55 (3951)	RP75 (4868)	UniProt (7208)	NCBI (9033)	Meta (37)
Jalview	View	View	View	View	View	View	View	View	View
HTML	View	View
PP/heatmap	₁	View

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (96)	Full (4914)	Representative proteomes				UniProt (7208)	NCBI (9033)	Meta (37)
	Seed (96)	Full (4914)	RP15 (1290)	RP35 (2677)	RP55 (3951)	RP75 (4868)	UniProt (7208)	NCBI (9033)	Meta (37)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (96)	Full (4914)	Representative proteomes				UniProt (7208)	NCBI (9033)	Meta (37)
	Seed (96)	Full (4914)	RP15 (1290)	RP35 (2677)	RP55 (3951)	RP75 (4868)	UniProt (7208)	NCBI (9033)	Meta (37)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	Download	Download	Download	Download	Download	Download

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

Pfam-B_303 (release 3.0)

Previous IDs:

synaptobrevin;

Type:

Family

Author:

Finn RD, Bateman A

Number in seed:

96

Number in full:

4914

Average length of the domain:

79.70 aa

Average identity of full alignment:

28 %

Average coverage of the sequence by the domain:

35.79 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	25.9	25.9
Trusted cut-off	25.9	25.9
Noise cut-off	25.8	25.8

Model length:

89

Family (HMM) version:

20

Download:

download the raw HMM for this family

Species distribution

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Colour assignments

Archea	Eukaryota
Bacteria	Other sequences
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Viroids	Unclassified sequence

Selections

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

superkingdom
kingdom
phylum
class
order
family
genus
species

Colouring and labels

Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

Anomalies in the taxonomy tree

There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.

Missing taxonomic levels

Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.

Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

Too many species/sequences

For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

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Tree controls

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The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
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Interactions

There are 11 interactions for this family. More...

SNAP-25 Synaptobrevin SNARE ANTH Synaphin Ank_2 Peptidase_M27 SNARE V-SNARE_C Synaphin Longin

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Synaptobrevin domain has been found. There are 56 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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Family: Synaptobrevin (PF00957)

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