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9  structures 66  species 0  interactions 229  sequences 2  architectures

Family: Synuclein (PF01387)

Summary: Synuclein

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 "Synuclein". More...

Synuclein Edit Wikipedia article

Synuclein
Identifiers
Symbol Synuclein
Pfam PF01387
InterPro IPR001058
SCOP 1xq8
SUPERFAMILY 1xq8
OPM superfamily 159
OPM protein 1xq8

Synucleins are a family of soluble proteins common to vertebrates, primarily expressed in neural tissue and in certain tumors.[1]

Family members[edit]

The synuclein family includes three known proteins: alpha-synuclein, beta-synuclein, and gamma-synuclein. Interest in the synuclein family began when alpha-synuclein was found to be mutated in several families with autosomal dominant Parkinson's disease.[2]

All synucleins have in common a highly conserved alpha-helical lipid-binding motif with similarity to the class-A2 lipid-binding domains of the exchangeable apolipoproteins. Synuclein family members are not found outside vertebrates, although they have some conserved structural similarity with plant 'late-embryo-abundant' proteins.[1]

Function[edit]

Normal cellular functions have not been determined for any of the synuclein proteins. Some data suggest a role in the regulation of membrane stability and/or turnover. Mutations in alpha-synuclein are associated with early-onset familial Parkinson's disease and the protein aggregates abnormally in Parkinson's disease, Alzheimer's disease, Lewy body disease, and other neurodegenerative diseases.[3][4] The gamma-synuclein protein's expression in breast tumors is a marker for tumor progression.[5][6]

Human proteins containing this domain[edit]

SNCA; SNCB; SNCG;

References[edit]

  1. ^ a b George JM (2002). "The synucleins". Genome Biol. 3 (1): REVIEWS3002. doi:10.1186/gb-2001-3-1-reviews3002. PMC 150459. PMID 11806835. 
  2. ^ Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A et al. (1997). "Mutation in the alpha-synuclein gene identified in families with Parkinson's disease.". Science 276 (5321): 2045–7. doi:10.1126/science.276.5321.2045. PMID 9197268. 
  3. ^ Mezey E, Dehejia A, Harta G, Papp MI, Polymeropoulos MH, Brownstein MJ (1998). "Alpha synuclein in neurodegenerative disorders: murderer or accomplice?". Nat Med 4 (7): 755–7. doi:10.1038/nm0798-755. PMID 9662355. 
  4. ^ Goedert M (July 2001). "Alpha-synuclein and neurodegenerative diseases". Nat. Rev. Neurosci. 2 (7): 492–501. doi:10.1038/35081564. PMID 11433374. 
  5. ^ Ji H, Liu YE, Jia T, Wang M, Liu J, Xiao G et al. (1997). "Identification of a breast cancer-specific gene, BCSG1, by direct differential cDNA sequencing.". Cancer Res 57 (4): 759–64. PMID 9044857. 
  6. ^ Bruening W, Giasson BI, Klein-Szanto AJ, Lee VM, Trojanowski JQ, Godwin AK (May 2000). "Synucleins are expressed in the majority of breast and ovarian carcinomas and in preneoplastic lesions of the ovary". Cancer 88 (9): 2154–63. doi:10.1002/(SICI)1097-0142(20000501)88:9<2154::AID-CNCR23>3.0.CO;2-9. PMID 10813729. 

External links[edit]


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.

Synuclein Provide feedback

There are three types of synucleins in humans, these are called alpha, beta and gamma. Alpha synuclein has been found mutated in families with autosomal dominant Parkinson's disease. A peptide of alpha synuclein has also been found in amyloid plaques in Alzheimer's patients.

Literature references

  1. Lavedan C; , Genome Res 1998;8:871-880.: The synuclein family. PUBMED:9750188 EPMC:9750188

  2. George JM; , Genome Biol 2002;3:REVIEWS3002.: The synucleins. PUBMED:11806835 EPMC:11806835


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001058

Synucleins are small, soluble proteins expressed primarily in neural tissue and in certain tumors [PUBMED:9750188, [PUBMED:11806835]. The family includes three known proteins: alpha-synuclein, beta-synuclein, and gamma-synuclein. All synucleins have in common a highly conserved alpha-helical lipid-binding motif with similarity to the class-A2 lipid-binding domains of the exchangeable apolipoproteins [PUBMED:10952980].

Synuclein family members are not found outside vertebrates, although they have some conserved structural similarity with plant 'late-embryo-abundant' proteins. The alpha- and beta-synuclein proteins are found primarily in brain tissue, where they are seen mainly in presynaptic terminals [PUBMED:7857654, PUBMED:7877458]. The gamma-synuclein protein is found primarily in the peripheral nervous system and retina, but its expression in breast tumors is a marker for tumor progression [PUBMED:9044857]. Normal cellular functions have not been determined for any of the synuclein proteins, although some data suggest a role in the regulation of membrane stability and/or turnover. Mutations in alpha-synuclein are associated with rare familial cases of early-onset Parkinson's disease, and the protein accumulates abnormally in Parkinson's disease, Alzheimer's disease, and several other neurodegenerative illnesses [PUBMED:11433374].

Domain organisation

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

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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...

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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
(229)
Representative proteomes NCBI
(186)
Meta
(0)
RP15
(4)
RP35
(10)
RP55
(31)
RP75
(81)
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Format an alignment

  Seed
(4)
Full
(229)
Representative proteomes NCBI
(186)
Meta
(0)
RP15
(4)
RP35
(10)
RP55
(31)
RP75
(81)
Alignment:
Format:
Order:
Sequence:
Gaps:
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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
(229)
Representative proteomes NCBI
(186)
Meta
(0)
RP15
(4)
RP35
(10)
RP55
(31)
RP75
(81)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped 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: [1]
Previous IDs: none
Type: Family
Author: Bateman A
Number in seed: 4
Number in full: 229
Average length of the domain: 111.10 aa
Average identity of full alignment: 60 %
Average coverage of the sequence by the domain: 94.74 %

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 21.1 21.1
Trusted cut-off 21.2 23.2
Noise cut-off 20.9 20.8
Model length: 131
Family (HMM) version: 12
Download: download the raw HMM for this family

Species distribution

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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 Synuclein domain has been found. There are 9 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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