P37840 (SYUA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	140 AA.
Sequence status	Complete.
Protein existence	Evidence 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 junction › synapse. 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.
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 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 component	Amyloid Cell junction Cytoplasm Membrane Nucleus Synapse
Coding sequence diversity	Alternative splicing
Disease	Alzheimer disease Disease mutation Neurodegeneration Parkinson disease Parkinsonism
Domain	Repeat
Ligand	Copper Metal-binding
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	activation 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: Compara aging Inferred from electronic annotation. Source: Compara behavioral response to cocaine Inferred from electronic annotation. Source: Compara 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: Compara cellular response to oxidative stress Inferred from electronic annotation. Source: Compara 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: Compara long-term synaptic potentiation Inferred from electronic annotation. Source: Compara microglial cell activation Inferred from electronic annotation. Source: Compara mitochondrial ATP synthesis coupled electron transport Inferred from electronic annotation. Source: Compara mitochondrial membrane organization Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from mutant phenotype PubMed 10818098. Source: UniProtKB negative regulation of dopamine metabolic process Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara 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: Compara phospholipid metabolic process Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara regulation of dopamine secretion Traceable author statement PubMed 21320589. Source: UniProtKB regulation of excitatory postsynaptic membrane potential Inferred from electronic annotation. Source: Compara regulation of glutamate secretion Inferred from electronic annotation. Source: Compara regulation of locomotion Inferred from electronic annotation. Source: Compara regulation of long-term neuronal synaptic plasticity Inferred from electronic annotation. Source: Compara regulation of macrophage activation Inferred from electronic annotation. Source: Compara regulation of phospholipase activity Inferred from direct assay PubMed 15641770. Source: UniProtKB response to drug Inferred from electronic annotation. Source: Compara 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: Compara synaptic vesicle endocytosis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: Compara 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 cytoplasmic vesicle membrane Inferred from electronic annotation. Source: Compara cytosol Inferred from direct assay Ref.1. Source: UniProtKB 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: Compara nuclear outer membrane Inferred from electronic annotation. Source: Compara 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: Compara rough endoplasmic reticulum Inferred from electronic annotation. Source: Compara synaptic vesicle Inferred from electronic annotation. Source: Compara terminal bouton Inferred from electronic annotation. Source: Compara
Molecular_function	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 ferrous iron binding Inferred from direct assay PubMed 11850416. Source: UniProtKB histone binding Inferred from direct assay PubMed 16959795. 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: Compara 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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		7	EBI-985879,EBI-985879
LRRK2	Q5S007	6	EBI-985879,EBI-5323863
RABAC1	Q9UI14	4	EBI-985879,EBI-712367

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 140

140

Alpha-synuclein

PRO_0000184022

Regions

Repeat

20 – 30

11

1

Repeat

31 – 41

11

2

Repeat

42 – 56

15

3; approximate

Repeat

57 – 67

11

4

Region

20 – 67

48

4 X 11 AA tandem repeats of [EGS]-K-T-K-[EQ]-[GQ]-V-X(4)

Sites

Metal binding

2

1

Copper Probable

Metal binding

50

1

Copper Probable

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.26

Modified residue

87

1

Phosphoserine; by CK2

Modified residue

125

1

Phosphotyrosine; by FYN Ref.15 Ref.21

Modified residue

129

1

Phosphoserine; by BARK1, CK2 and GRK5; alternate Ref.17

Modified residue

129

1

Phosphoserine; by PLK2; alternate Ref.17

Natural variations

Alternative sequence

41 – 54

14

Missing in isoform 2-5.

VSP_006363

Alternative sequence

103 – 130

28

Missing in isoform 2-4.

VSP_006364

Natural variant

30

1

A → P in PARK1. Ref.29

VAR_007957

Natural variant

46

1

E → K in PARK1 and DLB; significant increase in binding to negatively charged phospholipid liposomes. Ref.30 Ref.31

VAR_022703

Natural variant

53

1

A → T in PARK1; no effect on osmotic stress-induced phosphorylation. Ref.21 Ref.28

VAR_007454

Experimental info

Mutagenesis

2

1

D → A: Impairs copper-binding. Ref.25

Mutagenesis

39

1

Y → F: No effect on osmotic stress-induced phosphorylation. Ref.21

Mutagenesis

50

1

H → A: Impairs copper-binding. Ref.25

Mutagenesis

67 – 71

5

Missing: Reduces polymerization into amyloid fibrils. Ref.23

Mutagenesis

71 – 82

12

Missing: Impairs polymerization into amyloid fibrils. Ref.23

Mutagenesis

76 – 77

2

Missing: Impairs polymerization into amyloid fibrils. Ref.23

Mutagenesis

76

1

Missing: Does not affect polymerization into amyloid fibrils.

Mutagenesis

77

1

Missing: Does not affect polymerization into amyloid fibrils. Ref.23

Mutagenesis

78

1

Missing: Does not affect polymerization into amyloid fibrils. Ref.23

Mutagenesis

85 – 94

10

Missing: Reduces polymerization into amyloid fibrils. Ref.23

Mutagenesis

125

1

Y → F: Abolishes osmotic stress-induced phosphorylation. Ref.21

Mutagenesis

133

1

Y → F: No effect on osmotic stress-induced phosphorylation. Ref.21

Mutagenesis

136

1

Y → F: No effect on osmotic stress-induced phosphorylation. Ref.21

Secondary structure

1

.

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140

Helix Strand Turn

Details...

Helix

3 – 11

9

Helix

21 – 32

12

Helix

41 – 44

4

Helix

52 – 55

4

Helix

66 – 68

3

Beta strand

110 – 113

4

Turn

120 – 122

3

Turn

124 – 126

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (NACP140) [UniParc]. Last modified October 1, 1994. Version 1. Checksum: 6BB2F12128931663	FASTA	140	14,460
	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
	Isoform 2-4 (NACP112) [UniParc]. Checksum: 16EA234777EFA89E	FASTA	112	11,372
	10 20 30 40 50 60 MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GKTKEGVLYV GSKTKEGVVH GVATVAEKTK 70 80 90 100 110 EQVTNVGGAV VTGVTAVAQK TVEGAGSIAA ATGFVKKDQL GKEGYQDYEP EA
	Isoform 2-5 [UniParc]. Checksum: 0F87D9A60E831E02	FASTA	126	13,109
	10 20 30 40 50 60 MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GKTKEGVLYV VAEKTKEQVT NVGGAVVTGV 70 80 90 100 110 120 TAVAQKTVEG AGSIAAATGF VKKDQLGKNE EGAPQEGILE DMPVDPDNEA YEMPSEEGYQ DYEPEA

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, 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.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

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 , 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.

IPI

IPI00024107.
IPI00218467.
IPI00218468.

PIR

A49669.
S56746.

RefSeq

NP_000336.1. NM_000345.3.
NP_001139526.1. NM_001146054.1.
NP_001139527.1. NM_001146055.1.
NP_009292.1. NM_007308.2.

UniGene

Hs.21374.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XQ8	NMR	-	A	1-140	[»]
2JN5	NMR	-	A	1-12	[»]
2KKW	NMR	-	A	1-140	[»]
2X6M	X-ray	1.62	B	132-140	[»]
3Q25	X-ray	1.90	A	1-19	[»]
3Q26	X-ray	1.54	A	9-42	[»]
3Q27	X-ray	1.30	A	32-57	[»]
3Q28	X-ray	1.60	A	58-79	[»]
3Q29	X-ray	2.30	A/C	1-19	[»]

DisProt

DP00070.

ProteinModelPortal

P37840.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35354N.

IntAct

P37840. 188 interactions.

MINT

MINT-2515483.

STRING

9606.ENSP00000338345.

Protein family/group databases

TCDB

1.C.77.1.1. synuclein family.

PTM databases

PhosphoSite

P37840.

Polymorphism databases

DMDM

586067.

Proteomic databases

PaxDb

P37840.

PRIDE

P37840.

Protocols and materials databases

DNASU

6622.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000336904; ENSP00000338345; ENSG00000145335.
ENST00000345009; ENSP00000343683; ENSG00000145335.
ENST00000394986; ENSP00000378437; ENSG00000145335.
ENST00000394989; ENSP00000378440; ENSG00000145335.
ENST00000394991; ENSP00000378442; ENSG00000145335.
ENST00000420646; ENSP00000396241; ENSG00000145335.
ENST00000505199; ENSP00000421485; ENSG00000145335.
ENST00000506244; ENSP00000422238; ENSG00000145335.
ENST00000508895; ENSP00000426955; ENSG00000145335.

GeneID

6622.

KEGG

hsa:6622.

UCSC

uc003hso.3. human.
uc003hsp.3. human.
uc010ikt.3. human.

Organism-specific databases

CTD

6622.

GeneCards

GC04M090646.

HGNC

HGNC:11138. SNCA.

HPA

CAB010877.
HPA005459.

MIM

127750. phenotype.
163890. gene.
168600. phenotype.
168601. phenotype.
605543. phenotype.

neXtProt

NX_P37840.

Orphanet

1648. Lewy body dementia.
2828. Young adult-onset Parkinsonism.

PharmGKB

PA35986.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG44393.

HOGENOM

HOG000008691.

HOVERGEN

HBG000481.

InParanoid

P37840.

KO

K04528.

OMA

MPPEEEY.

Enzyme and pathway databases

Pathway_Interaction_DB

alphasynuclein_pathway. Alpha-synuclein signaling.

Reactome

REACT_116125. Disease.

Gene expression databases

ArrayExpress

P37840.

Bgee

P37840.

CleanEx

HS_SNCA.

Genevestigator

P37840.

GermOnline

ENSG00000145335. Homo sapiens.

Family and domain databases

Gene3D

1.10.287.700. 1 hit.

InterPro

IPR001058. Synuclein.
IPR002460. Synuclein_alpha.
[Graphical view]

PANTHER

PTHR13820. PTHR13820. 1 hit.

Pfam

PF01387. Synuclein. 1 hit.
[Graphical view]

PRINTS

PR01212. ASYNUCLEIN.
PR01211. SYNUCLEIN.

ProtoNet

Search...

Other

ChEMBL

CHEMBL6152.

ChiTaRS

SNCA. human.

DrugBank

DB01065. Melatonin.

EvolutionaryTrace

P37840.

GenomeRNAi

6622.

NextBio

25791.

PMAP-CutDB

P37840.

SOURCE

Search...

Entry information

Entry name

SYUA_HUMAN

Accession

Primary (citable) accession number: P37840
Secondary accession number(s): A8K2A4 , Q13701, Q4JHI3, Q6IAU6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	October 1, 1994
Last modified:	May 1, 2013
This is version 158 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.