Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
20  structures 99  species 2  interactions 298  sequences 8  architectures

Family: Synapsin_C (PF02750)

Summary: Synapsin, ATP binding domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Synapsin". More...

Synapsin Edit Wikipedia article

Synapsin, N-terminal domain
PDB 1auv EBI.jpg
Structure of the c domain of synapsin IA from bovine brain.[1]
Identifiers
Symbol Synapsin
Pfam PF02078
InterPro IPR001359
PROSITE PDOC00345
SCOP 1auv
SUPERFAMILY 1auv
OPM superfamily 131
OPM protein 1auv
Synapsin, ATP binding domain
Identifiers
Symbol Synapsin_C
Pfam PF02750
InterPro IPR001359
PROSITE PDOC00345
SCOP 1auv
SUPERFAMILY 1auv

The synapsins are a family of proteins that have long been implicated in the regulation of neurotransmitter release at synapses. Specifically, they are thought to be involved in regulating the number of synaptic vesicles available for release via exocytosis at any one time.[2]Synapsins are present in invertebrates and vertebrates and are somewhat homologous across evaluated vertebrates.

Current studies suggest the following hypothesis for the role of synapsin: synapsins bind synaptic vesicles to components of the cytoskeleton which prevents them from migrating to the presynaptic membrane and releasing transmitter. During an action potential, synapsins are phosphorylated by PKA (cAMP dependent protein kinase), releasing the synaptic vesicles and allowing them to move to the membrane and release their neurotransmitter.

Gene knockout studies in mice (where the mouse is unable to produce synapsin) have had some surprising results. Mice lacking all three synapsins are prone to seizures, and experience learning defects.[3] These results suggest that while synapsins are not essential for synaptic function, they do serve an important modulatory role. Conversely, studies using transgenic mice in which neuronal signaling is abolished in specific circuitries showed that synaptic activity regulates, but is not essential to maintain, the expression of these proteins.[4]

Family members[edit]

Humans and most other vertebrates possess three genes encoding three different synapsin proteins.[5] Each gene in turn is alternatively spliced to produce at least two different protein isoforms for a total of six isoforms:[6]

Gene Protein Isoforms
SYN1 Synapsin I Ia, Ib
SYN2 Synapsin II IIa, IIb
SYN3 Synapsin III IIIa, IIIb

Different neuron terminals will express varying amounts of each of these synapsin proteins and collectively these synapsins will comprise 1% of the total expressed protein at any one time.[7] Synapsin Ia has been implicated in bipolar disorder and schizophrenia.[8]

References[edit]

  1. ^ Esser L, Wang CR, Hosaka M, Smagula CS, Südhof TC, Deisenhofer J (February 1998). "Synapsin I is structurally similar to ATP-utilizing enzymes". EMBO J. 17 (4): 977–84. doi:10.1093/emboj/17.4.977. PMC 1170447. PMID 9463376. 
  2. ^ Evergren E, Benfenati F, Shupliakov O (September 2007). "The synapsin cycle: a view from the synaptic endocytic zone". J. Neurosci. Res. 85 (12): 2648–56. doi:10.1002/jnr.21176. PMID 17455288. 
  3. ^ Rosahl TW, Geppert M, Spillane D, Herz J, Hammer RE, Malenka RC, Sudhof TC (1993). "Short-term synaptic plasticity is altered in mice lacking synapsin I". Cell 75 (4): 661–670. doi:10.1016/0092-8674(93)90487-B. PMID 7902212. 
  4. ^ Kihara AH, Santos TO, Paschon V, Matos RJ, Britto LR (2008). "Lack of photoreceptor signaling alters the expression of specific synaptic proteins in the retina". Neuroscience 151 (4): 995–1005. doi:10.1016/j.neuroscience.2007.09.088. PMID 18248909. 
  5. ^ Kao HT, Porton B, Hilfiker S, Stefani G, Pieribone VA, DeSalle R, Greengard P (December 1999). "Molecular evolution of the synapsin gene family". J. Exp. Zool. 285 (4): 360–77. doi:10.1002/(SICI)1097-010X(19991215)285:4<360::AID-JEZ4>3.0.CO;2-3. PMID 10578110. 
  6. ^ Gitler D, Xu Y, Kao HT, Lin D, Lim S, Feng J, Greengard P, Augustine GJ (April 2004). "Molecular determinants of synapsin targeting to presynaptic terminals". J. Neurosci. 24 (14): 3711–20. doi:10.1523/JNEUROSCI.5225-03.2004. PMID 15071120. 
  7. ^ Ferreira A, Rapoport M (April 2002). "The synapsins: beyond the regulation of neurotransmitter release". Cell. Mol. Life Sci. 59 (4): 589–95. doi:10.1007/s00018-002-8451-5. PMID 12022468. 
  8. ^ Vawter, MP et al (April 2002). "Reduction of synapsin in the hippocampus of patients with bipolar disorder and schizophrenia". Mol. Psychiatry 7 (6): 571–8. doi:10.1038/sj.mp.4001158. PMID 12140780. 

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.

Synapsin, ATP binding domain Provide feedback

Ca dependent ATP binding in this ATP grasp fold. Function unknown.

Literature references

  1. Esser L, Wang CR, Hosaka M, Smagula CS, Sudhof TC, Deisenhofer J; , EMBO J 1998;17:977-984.: Synapsin I is structurally similar to ATP-utilizing enzymes. PUBMED:9463376 EPMC:9463376


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR020898

The synapsins are a family of neuron-specific phosphoproteins that coat synaptic vesicles and are involved in the binding between these vesicles and the cytoskeleton (including actin filaments). The family comprises 5 homologous proteins Ia, Ib, IIa, IIb and III. Synapsins I, II, and III are encoded by 3 different genes. The a and b isoforms of synapsin I and II are splice variants of the primary transcripts [PUBMED:10940454].

Synapsin I is mainly associated with regulation of neurotransmitter release from presynaptic neuron terminals [PUBMED:2859595]. Synapsin II, as well as being involved in neurotransmitter release, has a role in the synaptogenesis and synaptic plasticity responsible for long term potentiation [PUBMED:7777057]. Recent studies implicate synapsin III with a developmental role in neurite elongation and synapse formation that is distinct from the functions of synapsins I and II [PUBMED:10804215].

Structurally, synapsins are multidomain proteins, of which 3 domains are common to all the mammalian forms. The N-terminal `A' domain is ~30 residues long and contains a serine residue that serves as an acceptor site for protein kinase-mediated phosphorylation. This is followed by the `B' linker domain, which is ~80 residues long and is relatively poorly conserved. Domain `C' is the longest, spanning approximately 300 residues. This domain is highly conserved across all the synapsins (including those from Drosophila) and is possessed by all splice variants. The remaining six domains, D-I, are not shared by all the synapsins and differ both between the primary transcripts and the splice variants.

This entry represent the ATP-grasp fold found in synapsins, which is responsible for Ca dependent ATP binding.

Domain organisation

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

Loading domain graphics...

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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
(4)
Full
(298)
Representative proteomes NCBI
(323)
Meta
(10)
RP15
(29)
RP35
(39)
RP55
(95)
RP75
(154)
Jalview View  View  View  View  View  View  View  View 
HTML View  View  View  View  View  View     
PP/heatmap 1 View  View  View  View  View     
Pfam viewer View  View             

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

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(4)
Full
(298)
Representative proteomes NCBI
(323)
Meta
(10)
RP15
(29)
RP35
(39)
RP55
(95)
RP75
(154)
Alignment:
Format:
Order:
Sequence:
Gaps:
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
(4)
Full
(298)
Representative proteomes NCBI
(323)
Meta
(10)
RP15
(29)
RP35
(39)
RP55
(95)
RP75
(154)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped 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.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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 View help on the curation process

Seed source: IPR001359
Previous IDs: none
Type: Domain
Author: Mian N, Bateman A, Griffiths-Jones SR
Number in seed: 4
Number in full: 298
Average length of the domain: 166.60 aa
Average identity of full alignment: 58 %
Average coverage of the sequence by the domain: 35.89 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.5 22.5
Trusted cut-off 22.5 22.5
Noise cut-off 22.4 22.4
Model length: 203
Family (HMM) version: 9
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

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...

Loading sunburst data...

Tree controls

Hide

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

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There are 2 interactions for this family. More...

Synapsin_C Synapsin

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 Synapsin_C domain has been found. There are 20 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.

Loading structure mapping...