Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P37840 (SYUA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 169. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alpha-synuclein
Alternative name(s):
Non-A beta component of AD amyloid
Non-A4 component of amyloid precursor
Short name=NACP
Gene names
Name:SNCA
Synonyms:NACP, PARK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length140 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May be involved in the regulation of dopamine release and transport. Induces fibrillization of microtubule-associated protein tau. Reduces neuronal responsiveness to various apoptotic stimuli, leading to a decreased caspase-3 activation.

Subunit structure

Soluble monomer which can form filamentous aggregates. Interacts with UCHL1 By similarity. Interacts with phospholipase D and histones. Ref.16 Ref.18

Subcellular location

Cytoplasm. Membrane. Nucleus. Cell junctionsynapse. Note: Membrane-bound in dopaminergic neurons. Ref.18 Ref.22

Tissue specificity

Expressed principally in brain but is also expressed in low concentrations in all tissues examined except in liver. Concentrated in presynaptic nerve terminals.

Domain

The 'non A-beta component of Alzheimer disease amyloid plaque' domain (NAC domain) is involved in fibrils formation. The middle hydrophobic region forms the core of the filaments. The C-terminus may regulate aggregation and determine the diameter of the filaments. Ref.23

Post-translational modification

Phosphorylated, predominantly on serine residues. Phosphorylation by CK1 appears to occur on residues distinct from the residue phosphorylated by other kinases. Phosphorylation of Ser-129 is selective and extensive in synucleinopathy lesions. In vitro, phosphorylation at Ser-129 promoted insoluble fibril formation. Phosphorylated on Tyr-125 by a PTK2B-dependent pathway upon osmotic stress. Ref.13 Ref.14 Ref.15 Ref.17 Ref.21

Hallmark lesions of neurodegenerative synucleinopathies contain alpha-synuclein that is modified by nitration of tyrosine residues and possibly by dityrosine cross-linking to generated stable oligomers.

Ubiquitinated. The predominant conjugate is the diubiquitinated form By similarity.

Acetylation at Met-1 seems to be important for proper folding and native oligomeric structure. Ref.26

Involvement in disease

Genetic alterations of SNCA resulting in aberrant polymerization into fibrils, are associated with several neurodegenerative diseases (synucleinopathies). SNCA fibrillar aggregates represent the major non A-beta component of Alzheimer disease amyloid plaque, and a major component of Lewy body inclusions. They are also found within Lewy body (LB)-like intraneuronal inclusions, glial inclusions and axonal spheroids in neurodegeneration with brain iron accumulation type 1.

Parkinson disease 1 (PARK1) [MIM:168601]: A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.28 Ref.29 Ref.30 Ref.32 Ref.33

Parkinson disease 4 (PARK4) [MIM:605543]: A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (resting tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Dementia Lewy body (DLB) [MIM:127750]: A neurodegenerative disorder characterized by mental impairment leading to dementia, parkinsonism, fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Brainstem or cortical intraneuronal accumulations of aggregated proteins (Lewy bodies) are the only essential pathologic features. Patients may also have hippocampal and neocortical senile plaques, sometimes in sufficient number to fulfill the diagnostic criteria for Alzheimer disease.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Sequence similarities

Belongs to the synuclein family.

Ontologies

Keywords
   Cellular componentAmyloid
Cell junction
Cytoplasm
Membrane
Nucleus
Synapse
   Coding sequence diversityAlternative splicing
   DiseaseAlzheimer disease
Disease mutation
Neurodegeneration
Parkinson disease
Parkinsonism
   DomainRepeat
   LigandCopper
Metal-binding
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 21050448. Source: BHF-UCL

adult locomotory behavior

Inferred from electronic annotation. Source: Ensembl

aging

Inferred from electronic annotation. Source: Ensembl

behavioral response to cocaine

Inferred from electronic annotation. Source: Ensembl

cellular response to copper ion

Inferred from direct assay PubMed 21320589. Source: UniProtKB

cellular response to epinephrine stimulus

Traceable author statement PubMed 21320589. Source: UniProtKB

cellular response to fibroblast growth factor stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to oxidative stress

Inferred from electronic annotation. Source: Ensembl

dopamine biosynthetic process

Traceable author statement PubMed 21320589. Source: UniProtKB

dopamine uptake involved in synaptic transmission

Traceable author statement PubMed 21320589. Source: UniProtKB

extracellular fibril organization

Traceable author statement PubMed 21320589. Source: UniProtKB

fatty acid metabolic process

Inferred from electronic annotation. Source: Ensembl

long-term synaptic potentiation

Inferred from electronic annotation. Source: Ensembl

microglial cell activation

Inferred from electronic annotation. Source: Ensembl

mitochondrial ATP synthesis coupled electron transport

Inferred from electronic annotation. Source: Ensembl

mitochondrial membrane organization

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 10818098. Source: UniProtKB

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from mutant phenotype PubMed 10818098. Source: UniProtKB

negative regulation of dopamine metabolic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of dopamine uptake involved in synaptic transmission

Inferred from direct assay PubMed 12958153. Source: UniProtKB

negative regulation of exocytosis

Inferred from mutant phenotype PubMed 12239163. Source: UniProtKB

negative regulation of histone acetylation

Inferred from direct assay PubMed 16959795. Source: UniProtKB

negative regulation of microtubule polymerization

Inferred from direct assay PubMed 21127069. Source: BHF-UCL

negative regulation of monooxygenase activity

Inferred from direct assay PubMed 11943812. Source: BHF-UCL

negative regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of norepinephrine uptake

Inferred from direct assay PubMed 17156375. Source: UniProtKB

negative regulation of platelet-derived growth factor receptor signaling pathway

Inferred from direct assay PubMed 12239163. Source: UniProtKB

negative regulation of protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

negative regulation of serotonin uptake

Inferred from direct assay PubMed 16882008. Source: UniProtKB

negative regulation of thrombin receptor signaling pathway

Inferred from direct assay PubMed 12239163. Source: UniProtKB

negative regulation of transporter activity

Inferred from direct assay PubMed 16882008. Source: UniProtKB

neutral lipid metabolic process

Inferred from electronic annotation. Source: Ensembl

oxidation-reduction process

Inferred from direct assay PubMed 21320589. Source: UniProtKB

phospholipid metabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of endocytosis

Inferred from direct assay PubMed 18980610. Source: UniProtKB

positive regulation of inositol phosphate biosynthetic process

Inferred from direct assay PubMed 15641770. Source: UniProtKB

positive regulation of neurotransmitter secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-serine phosphorylation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of protein serine/threonine kinase activity

Inferred from direct assay PubMed 21127069. Source: BHF-UCL

positive regulation of receptor recycling

Inferred from direct assay PubMed 18980610. Source: UniProtKB

positive regulation of release of sequestered calcium ion into cytosol

Inferred from direct assay PubMed 15641770. Source: UniProtKB

protein destabilization

Inferred from direct assay PubMed 21320589. Source: UniProtKB

receptor internalization

Inferred from direct assay PubMed 18980610. Source: UniProtKB

regulation of acyl-CoA biosynthetic process

Inferred from electronic annotation. Source: Ensembl

regulation of dopamine secretion

Traceable author statement PubMed 21320589. Source: UniProtKB

regulation of excitatory postsynaptic membrane potential

Inferred from electronic annotation. Source: Ensembl

regulation of glutamate secretion

Inferred from electronic annotation. Source: Ensembl

regulation of locomotion

Inferred from electronic annotation. Source: Ensembl

regulation of long-term neuronal synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

regulation of macrophage activation

Inferred from electronic annotation. Source: Ensembl

regulation of phospholipase activity

Inferred from direct assay PubMed 15641770. Source: UniProtKB

response to drug

Inferred from electronic annotation. Source: Ensembl

response to interferon-gamma

Inferred from direct assay PubMed 19157893. Source: UniProtKB

response to interleukin-1

Inferred from direct assay PubMed 12406186. Source: UniProtKB

response to iron(II) ion

Inferred from direct assay PubMed 11850416. Source: UniProtKB

response to lipopolysaccharide

Inferred from direct assay PubMed 12406186. Source: UniProtKB

response to magnesium ion

Inferred from direct assay PubMed 11850416. Source: UniProtKB

synapse organization

Inferred from electronic annotation. Source: Ensembl

synaptic vesicle endocytosis

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

actin cytoskeleton

Inferred from direct assay PubMed 17408955. Source: UniProtKB

axon

Inferred from direct assay PubMed 12958153. Source: UniProtKB

cell cortex

Inferred from direct assay PubMed 19157893. Source: UniProtKB

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Inferred from direct assay PubMed 12406186PubMed 12958153PubMed 16959795PubMed 17408955. Source: UniProtKB

cytoplasmic vesicle membrane

Inferred from electronic annotation. Source: Ensembl

cytosol

Inferred from direct assay Ref.1. Source: UniProtKB

extracellular region

Traceable author statement. Source: Reactome

fibril

Inferred from direct assay PubMed 18346205. Source: UniProtKB

growth cone

Inferred from direct assay PubMed 12958153. Source: UniProtKB

inclusion body

Inferred from direct assay PubMed 20039155. Source: UniProtKB

mitochondrion

Inferred from electronic annotation. Source: Ensembl

nuclear outer membrane

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 12406186PubMed 16959795PubMed 17408955. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay PubMed 20039155. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 12958153PubMed 15641770. Source: UniProtKB

ribosome

Inferred from electronic annotation. Source: Ensembl

rough endoplasmic reticulum

Inferred from electronic annotation. Source: Ensembl

synaptic vesicle

Inferred from electronic annotation. Source: Ensembl

terminal bouton

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionHsp70 protein binding

Inferred from physical interaction PubMed 18975920. Source: UniProtKB

alpha-tubulin binding

Inferred from physical interaction PubMed 11698390. Source: UniProtKB

calcium ion binding

Inferred from direct assay PubMed 11312271PubMed 11850416. Source: UniProtKB

copper ion binding

Inferred from direct assay Ref.25PubMed 21320589. Source: UniProtKB

cysteine-type endopeptidase inhibitor activity involved in apoptotic process

Inferred from direct assay PubMed 10818098. Source: UniProtKB

dynein binding

Inferred from physical interaction PubMed 16176937. Source: UniProtKB

ferrous iron binding

Inferred from direct assay PubMed 11850416. Source: UniProtKB

histone binding

Inferred from direct assay PubMed 16959795. Source: UniProtKB

identical protein binding

Inferred from physical interaction PubMed 16330551PubMed 16764865PubMed 18614564PubMed 19745811PubMed 19875982PubMed 21443877PubMed 22119730PubMed 23927048PubMed 24374342. Source: IntAct

kinesin binding

Inferred from physical interaction PubMed 16176937. Source: UniProtKB

magnesium ion binding

Inferred from direct assay PubMed 11850416. Source: UniProtKB

oxidoreductase activity

Inferred from direct assay PubMed 21320589. Source: UniProtKB

phospholipid binding

Inferred from electronic annotation. Source: Ensembl

phosphoprotein binding

Inferred from direct assay PubMed 21127069. Source: BHF-UCL

tau protein binding

Inferred from direct assay PubMed 17408955. Source: UniProtKB

zinc ion binding

Inferred from direct assay PubMed 11850416. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P37840-1)

Also known as: NACP140;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2-4 (identifier: P37840-2)

Also known as: NACP112;

The sequence of this isoform differs from the canonical sequence as follows:
     103-130: Missing.
Isoform 2-5 (identifier: P37840-3)

The sequence of this isoform differs from the canonical sequence as follows:
     41-54: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 140140Alpha-synuclein
PRO_0000184022

Regions

Repeat20 – 30111
Repeat31 – 41112
Repeat42 – 56153; approximate
Repeat57 – 67114
Region20 – 67484 X 11 AA tandem repeats of [EGS]-K-T-K-[EQ]-[GQ]-V-X(4)

Sites

Metal binding21Copper Probable
Metal binding501Copper Probable

Amino acid modifications

Modified residue11N-acetylmethionine Ref.26
Modified residue871Phosphoserine; by CK2
Modified residue1251Phosphotyrosine; by FYN Ref.15 Ref.21
Modified residue1291Phosphoserine; by BARK1, CK2 and GRK5; alternate Ref.17
Modified residue1291Phosphoserine; by PLK2; alternate Ref.17

Natural variations

Alternative sequence41 – 5414Missing in isoform 2-5.
VSP_006363
Alternative sequence103 – 13028Missing in isoform 2-4.
VSP_006364
Natural variant301A → P in PARK1. Ref.29
VAR_007957
Natural variant461E → K in PARK1 and DLB; significant increase in binding to negatively charged phospholipid liposomes. Ref.30 Ref.31
VAR_022703
Natural variant501H → Q in PARK1; impairs copper-binding. Ref.32 Ref.33
VAR_070171
Natural variant531A → T in PARK1; no effect on osmotic stress-induced phosphorylation. Ref.21 Ref.28
VAR_007454

Experimental info

Mutagenesis21D → A: Impairs copper-binding. Ref.25
Mutagenesis391Y → F: No effect on osmotic stress-induced phosphorylation. Ref.21
Mutagenesis501H → A: Impairs copper-binding. Ref.25
Mutagenesis67 – 715Missing: Reduces polymerization into amyloid fibrils. Ref.23
Mutagenesis71 – 8212Missing: Impairs polymerization into amyloid fibrils. Ref.23
Mutagenesis76 – 772Missing: Impairs polymerization into amyloid fibrils. Ref.23
Mutagenesis761Missing: Does not affect polymerization into amyloid fibrils.
Mutagenesis771Missing: Does not affect polymerization into amyloid fibrils. Ref.23
Mutagenesis781Missing: Does not affect polymerization into amyloid fibrils. Ref.23
Mutagenesis85 – 9410Missing: Reduces polymerization into amyloid fibrils. Ref.23
Mutagenesis1251Y → F: Abolishes osmotic stress-induced phosphorylation. Ref.21
Mutagenesis1331Y → F: No effect on osmotic stress-induced phosphorylation. Ref.21
Mutagenesis1361Y → F: No effect on osmotic stress-induced phosphorylation. Ref.21

Secondary structure

................. 140
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (NACP140) [UniParc].

Last modified October 1, 1994. Version 1.
Checksum: 6BB2F12128931663

FASTA14014,460
        10         20         30         40         50         60 
MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GKTKEGVLYV GSKTKEGVVH GVATVAEKTK 

        70         80         90        100        110        120 
EQVTNVGGAV VTGVTAVAQK TVEGAGSIAA ATGFVKKDQL GKNEEGAPQE GILEDMPVDP 

       130        140 
DNEAYEMPSE EGYQDYEPEA 

« Hide

Isoform 2-4 (NACP112) [UniParc].

Checksum: 16EA234777EFA89E
Show »

FASTA11211,372
Isoform 2-5 [UniParc].

Checksum: 0F87D9A60E831E02
Show »

FASTA12613,109

References

« Hide 'large scale' references
[1]"Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease."
Ueda K., Fukushima H., Masliah E., Xia Y., Iwai A., Yoshimoto M., Otero D.A., Kondo J., Ihara Y., Saitoh T.
Proc. Natl. Acad. Sci. U.S.A. 90:11282-11286(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 61-95.
Tissue: Brain.
[2]"The NACP/synuclein gene: chromosomal assignment and screening for alterations in Alzheimer disease."
Campion D., Martin C., Heilig R., Charbonnier F., Moreau V., Flaman J.-M., Petit J.-L., Hannequin D., Brice A., Frebourg T.
Genomics 26:254-257(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2-4 AND 2-5).
[3]"Tissue-dependent alternative splicing of mRNA for NACP, the precursor of non-A beta component of Alzheimer's disease amyloid."
Ueda K., Saitoh T., Mori H.
Biochem. Biophys. Res. Commun. 205:1366-1372(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2-4).
Tissue: Brain.
[4]Xia Y., Silva R.D., Chen X.H., Saitoh T.
Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Human and mouse alpha-synuclein genes: comparative genomic sequence analysis and identification of a novel gene regulatory element."
Touchman J.W., Dehejia A., Chiba-Falek O., Cabin D.E., Schwartz J.R., Orrison B.M., Polymeropoulos M.H., Nussbaum R.L.
Genome Res. 11:78-86(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2-4).
[6]Hu X., Xu Y., Peng X., Yuan J., Qiang B.
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[7]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Thalamus.
[8]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[9]NIEHS SNPs program
Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[10]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Uterus.
[12]Lubec G., Chen W.-Q., Sun Y.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 59-96, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Fetal brain cortex.
[13]"Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein."
Okochi M., Walter J., Koyama A., Nakajo S., Baba M., Iwatsubo T., Meijer L., Kahle P.J., Haass C.
J. Biol. Chem. 275:390-397(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY CASEIN KINASE.
[14]"Synucleins are a novel class of substrates for G protein-coupled receptor kinases."
Pronin A.N., Morris A.J., Surguchov A., Benovic J.L.
J. Biol. Chem. 275:26515-26522(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY G-PROTEIN COUPLED RECEPTOR KINASE.
[15]"Activated Fyn phosphorylates alpha-synuclein at tyrosine residue 125."
Nakamura T., Yamashita H., Takahashi T., Nakamura S.
Biochem. Biophys. Res. Commun. 280:1085-1092(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-125 BY FYN.
[16]"Alpha-synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase D activation in human embryonic kidney-293 cells."
Ahn B.H., Rhim H., Kim S.Y., Sung Y.M., Lee M.Y., Choi J.Y., Wolozin B., Chang J.S., Lee Y.H., Kwon T.K., Chung K.C., Yoon S.H., Hahn S.J., Kim M.S., Jo Y.H., Min do S.
J. Biol. Chem. 277:12334-12342(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PHOSPHOLIPASE D.
[17]"alpha-Synuclein is phosphorylated in synucleinopathy lesions."
Fujiwara H., Hasegawa M., Dohmae N., Kawashima A., Masliah E., Goldberg M.S., Shen J., Takio K., Iwatsubo T.
Nat. Cell Biol. 4:160-164(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-129.
[18]"Nuclear localization of alpha-synuclein and its interaction with histones."
Goers J., Manning-Bog A.B., McCormack A.L., Millett I.S., Doniach S., Di Monte D.A., Uversky V.N., Fink A.L.
Biochemistry 42:8465-8471(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HISTONES, SUBCELLULAR LOCATION.
[19]"Role of alpha-synuclein carboxy-terminus on fibril formation in vitro."
Murray I.V., Giasson B.I., Quinn S.M., Koppaka V., Axelsen P.H., Ischiropoulos H., Trojanowski J.Q., Lee V.M.
Biochemistry 42:8530-8540(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: ROLE OF THE C-TERMINUS IN FIBRILLOGENESIS.
[20]"Recent advances on alpha-synuclein cell biology: functions and dysfunctions."
Alves da Costa C.
Curr. Mol. Med. 3:17-24(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[21]"Identification and characterization of a novel Pyk2/related adhesion focal tyrosine kinase-associated protein that inhibits alpha-synuclein phosphorylation."
Takahashi T., Yamashita H., Nagano Y., Nakamura T., Ohmori H., Avraham H., Avraham S., Yasuda M., Matsumoto M.
J. Biol. Chem. 278:42225-42233(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF TYR-39; TYR-125; TYR-133 AND TYR-136, CHARACTERIZATION OF VARIANT THR-53, PHOSPHORYLATION AT TYR-125.
[22]"Lipid rafts mediate the synaptic localization of alpha-synuclein."
Fortin D.L., Troyer M.D., Nakamura K., Kubo S., Anthony M.D., Edwards R.H.
J. Neurosci. 24:6715-6723(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[23]"Characterization of hydrophobic residue requirements for alpha-synuclein fibrillization."
Waxman E.A., Mazzulli J.R., Giasson B.I.
Biochemistry 48:9427-9436(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FIBRILS FORMATION, DOMAIN NAC, MUTAGENESIS OF 67-GLY--VAL-71; 71-VAL--VAL-82; 76-ALA-VAL-77; VAL-77; ALA-78 AND 85-ALA--PHE-94.
[24]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[25]"Coordination features and affinity of the Cu(2)+ site in the alpha-synuclein protein of Parkinson's disease."
Dudzik C.G., Walter E.D., Millhauser G.L.
Biochemistry 50:1771-1777(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: COPPER-BINDING, MUTAGENESIS OF ASP-2 AND HIS-50.
[26]"N-Terminal acetylation is critical for forming alpha-helical oligomer of alpha-synuclein."
Trexler A.J., Rhoades E.
Protein Sci. 21:601-605(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT MET-1.
[27]"Structure and dynamics of micelle-bound human alpha-synuclein."
Ulmer T.S., Bax A., Cole N.B., Nussbaum R.L.
J. Biol. Chem. 280:9595-9603(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR IN COMPLEX WITH DETERGENT MICELLES.
[28]"Mutation in the alpha-synuclein gene identified in families with Parkinson's disease."
Polymeropoulos M.H., Lavedan C., Leroy E., Ide S.E., Dehejia A., Dutra A., Pike B., Root H., Rubenstein J., Boyer R., Stenroos E.S., Chandrasekharappa S., Athanassiadou A., Papapetropoulos T., Johnson W.G., Lazzarini A.M., Duvoisin R.C., di Iorio G., Golbe L.I., Nussbaum R.L.
Science 276:2045-2047(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK1 THR-53.
[29]"Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease."
Krueger R., Kuhn W., Mueller T., Woitalla D., Graeber M., Koesel S., Przuntek H., Epplen J.T., Schoels L., Riess O.
Nat. Genet. 18:106-108(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK1 PRO-30.
[30]"The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia."
Zarranz J.J., Alegre J., Gomez-Esteban J.C., Lezcano E., Ros R., Ampuero I., Vidal L., Hoenicka J., Rodriguez O., Atares B., Llorens V., Gomez Tortosa E., del Ser T., Munoz D.G., de Yebenes J.G.
Ann. Neurol. 55:164-173(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK1/DLB LYS-46.
[31]"Mutation E46K increases phospholipid binding and assembly into filaments of human alpha-synuclein."
Choi W., Zibaee S., Jakes R., Serpell L.C., Davletov B., Crowther R.A., Goedert M.
FEBS Lett. 576:363-368(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT LYS-46.
[32]"Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease."
Appel-Cresswell S., Vilarino-Guell C., Encarnacion M., Sherman H., Yu I., Shah B., Weir D., Thompson C., Szu-Tu C., Trinh J., Aasly J.O., Rajput A., Rajput A.H., Jon Stoessl A., Farrer M.J.
Mov. Disord. 28:811-813(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK1 GLN-50.
[33]"A novel alpha-synuclein missense mutation in Parkinson disease."
Proukakis C., Dudzik C.G., Brier T., MacKay D.S., Cooper J.M., Millhauser G.L., Houlden H., Schapira A.H.
Neurology 80:1062-1064(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK1 GLN-50, CHARACTERIZATION OF VARIANT PARK1 GLN-50.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L08850 mRNA. Translation: AAA16117.1.
L36674 mRNA. Translation: AAA98493.1.
L36675 mRNA. Translation: AAA98487.1.
D31839 mRNA. Translation: BAA06625.1.
U46901 expand/collapse EMBL AC list , U46897, U46898, U46899 Genomic DNA. Translation: AAC02114.1.
AF163864 Genomic DNA. Translation: AAG30302.1.
AF163864 Genomic DNA. Translation: AAG30303.1.
AY049786 mRNA. Translation: AAL15443.1.
AK290169 mRNA. Translation: BAF82858.1.
CR457058 mRNA. Translation: CAG33339.1.
DQ088379 Genomic DNA. Translation: AAY88735.1.
CH471057 Genomic DNA. Translation: EAX06036.1.
BC013293 mRNA. Translation: AAH13293.1.
BC108275 mRNA. Translation: AAI08276.1.
PIRA49669.
S56746.
RefSeqNP_000336.1. NM_000345.3.
NP_001139526.1. NM_001146054.1.
NP_001139527.1. NM_001146055.1.
NP_009292.1. NM_007308.2.
UniGeneHs.21374.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1XQ8NMR-A1-140[»]
2JN5NMR-A1-12[»]
2KKWNMR-A1-140[»]
2M55NMR-B1-19[»]
2X6MX-ray1.62B132-140[»]
3Q25X-ray1.90A1-19[»]
3Q26X-ray1.54A9-42[»]
3Q27X-ray1.30A32-57[»]
3Q28X-ray1.60A58-79[»]
3Q29X-ray2.30A/C1-19[»]
DisProtDP00070.
ProteinModelPortalP37840.
SMRP37840. Positions 1-140.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112506. 410 interactions.
DIPDIP-35354N.
IntActP37840. 208 interactions.
MINTMINT-2515483.
STRING9606.ENSP00000338345.

Chemistry

ChEMBLCHEMBL6152.
DrugBankDB01065. Melatonin.

Protein family/group databases

TCDB1.C.77.1.1. the synuclein (synuclein) family.

PTM databases

PhosphoSiteP37840.

Polymorphism databases

DMDM586067.

Proteomic databases

PaxDbP37840.
PRIDEP37840.

Protocols and materials databases

DNASU6622.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000336904; ENSP00000338345; ENSG00000145335. [P37840-1]
ENST00000345009; ENSP00000343683; ENSG00000145335. [P37840-2]
ENST00000394986; ENSP00000378437; ENSG00000145335. [P37840-1]
ENST00000394989; ENSP00000378440; ENSG00000145335. [P37840-3]
ENST00000394991; ENSP00000378442; ENSG00000145335. [P37840-1]
ENST00000420646; ENSP00000396241; ENSG00000145335. [P37840-2]
ENST00000505199; ENSP00000421485; ENSG00000145335. [P37840-3]
ENST00000506244; ENSP00000422238; ENSG00000145335. [P37840-1]
ENST00000508895; ENSP00000426955; ENSG00000145335. [P37840-1]
GeneID6622.
KEGGhsa:6622.
UCSCuc003hsp.3. human. [P37840-1]

Organism-specific databases

CTD6622.
GeneCardsGC04M090646.
HGNCHGNC:11138. SNCA.
HPACAB010877.
HPA005459.
MIM127750. phenotype.
163890. gene.
168600. phenotype.
168601. phenotype.
605543. phenotype.
neXtProtNX_P37840.
Orphanet1648. Dementia with Lewy body.
171695. Parkinsonian-pyramidal syndrome.
2828. Young adult-onset Parkinsonism.
PharmGKBPA35986.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG44393.
HOGENOMHOG000008691.
HOVERGENHBG000481.
InParanoidP37840.
KOK04528.
OMASEAYEMP.
OrthoDBEOG7034KG.
PhylomeDBP37840.
TreeFamTF332776.

Enzyme and pathway databases

ReactomeREACT_116125. Disease.
SignaLinkP37840.

Gene expression databases

ArrayExpressP37840.
BgeeP37840.
CleanExHS_SNCA.
GenevestigatorP37840.

Family and domain databases

Gene3D1.10.287.700. 1 hit.
InterProIPR001058. Synuclein.
IPR002460. Synuclein_alpha.
[Graphical view]
PANTHERPTHR13820. PTHR13820. 1 hit.
PfamPF01387. Synuclein. 1 hit.
[Graphical view]
PRINTSPR01212. ASYNUCLEIN.
PR01211. SYNUCLEIN.
ProtoNetSearch...

Other

ChiTaRSSNCA. human.
EvolutionaryTraceP37840.
GeneWikiAlpha-synuclein.
GenomeRNAi6622.
NextBio25791.
PMAP-CutDBP37840.
PROP37840.
SOURCESearch...

Entry information

Entry nameSYUA_HUMAN
AccessionPrimary (citable) accession number: P37840
Secondary accession number(s): A8K2A4 expand/collapse secondary AC list , Q13701, Q4JHI3, Q6IAU6
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 1, 1994
Last modified: April 16, 2014
This is version 169 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM