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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.17
Subcellular location	Cytoplasm. Membrane. Nucleus. Cell junction › synapse. Note: Membrane-bound in dopaminergic neurons. Ref.17 Ref.21
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.22
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.20 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.
Involvement in disease	Note=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. Defects in SNCA are the cause of Parkinson disease type 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. Ref.25 Ref.26 Ref.27 Defects in SNCA are the cause of Parkinson disease type 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 (tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia. Defects in SNCA are the cause of dementia Lewy body (DLB) [MIM:127750]. A neurodegenerative disorder clinically characterized by mental impairment leading to dementia, parkinsonism, often with 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.
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
PTM	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. Source: BHF-UCL anti-apoptosis Inferred from mutant phenotype. Source: UniProtKB negative regulation of dopamine uptake Inferred from direct assay. Source: UniProtKB negative regulation of exocytosis Inferred from mutant phenotype. Source: UniProtKB negative regulation of histone acetylation Inferred from direct assay. Source: UniProtKB negative regulation of microtubule polymerization Inferred from direct assay. Source: BHF-UCL negative regulation of monooxygenase activity Inferred from direct assay. Source: BHF-UCL negative regulation of norepinephrine uptake Inferred from direct assay. Source: UniProtKB negative regulation of platelet-derived growth factor receptor signaling pathway Inferred from direct assay. Source: UniProtKB negative regulation of serotonin uptake Inferred from direct assay. Source: UniProtKB negative regulation of thrombin receptor signaling pathway Inferred from direct assay. Source: UniProtKB negative regulation of transporter activity Inferred from direct assay. Source: UniProtKB positive regulation of endocytosis Inferred from direct assay. Source: UniProtKB positive regulation of inositol phosphate biosynthetic process Inferred from direct assay. Source: UniProtKB 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. Source: BHF-UCL positive regulation of receptor recycling Inferred from direct assay. Source: UniProtKB positive regulation of release of sequestered calcium ion into cytosol Inferred from direct assay. Source: UniProtKB receptor internalization Inferred from direct assay. Source: UniProtKB regulation of phospholipase activity Inferred from direct assay. Source: UniProtKB response to interferon-gamma Inferred from direct assay. Source: UniProtKB response to interleukin-1 Inferred from direct assay. Source: UniProtKB response to iron(II) ion Inferred from direct assay. Source: UniProtKB response to lipopolysaccharide Inferred from direct assay. Source: UniProtKB response to magnesium ion Inferred from direct assay. Source: UniProtKB synaptic vesicle endocytosis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	actin cytoskeleton Inferred from direct assay. Source: UniProtKB axon Inferred from direct assay. Source: UniProtKB cell cortex Inferred from direct assay. Source: UniProtKB cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytosol Inferred from direct assay Ref.1. Source: UniProtKB fibril Inferred from direct assay. Source: UniProtKB growth cone Inferred from direct assay. Source: UniProtKB nucleus Inferred from direct assay. Source: UniProtKB plasma membrane Inferred from direct assay. Source: UniProtKB synapse Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	Hsp70 protein binding Inferred from physical interaction. Source: UniProtKB alpha-tubulin binding Inferred from physical interaction. Source: UniProtKB calcium ion binding Inferred from direct assay. Source: UniProtKB cysteine-type endopeptidase inhibitor activity involved in apoptotic process Inferred from direct assay. Source: UniProtKB dynein binding Inferred from physical interaction. Source: UniProtKB ferrous iron binding Inferred from direct assay. Source: UniProtKB histone binding Inferred from direct assay. Source: UniProtKB identical protein binding Inferred from physical interaction. Source: IntAct kinesin binding Inferred from physical interaction. Source: UniProtKB magnesium ion binding Inferred from direct assay. Source: UniProtKB phosphoprotein binding Inferred from direct assay. Source: BHF-UCL tau protein binding Inferred from direct assay. Source: UniProtKB zinc ion binding Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-985879,EBI-985879

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)

Amino acid modifications

Modified residue

87

1

Phosphoserine; by CK2

Modified residue

125

1

Phosphotyrosine; by FYN Ref.15 Ref.20

Modified residue

129

1

Phosphoserine; by BARK1, CK2 and GRK5

Modified residue

129

1

Phosphoserine; by PLK2 By similarity

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.26

VAR_007957

Natural variant

46

1

E → K in PARK1 and DLB; significant increase in binding to negatively charged phospholipid liposomes. Ref.27 Ref.28

VAR_022703

Natural variant

53

1

A → T in PARK1; no effect on osmotic stress-induced phosphorylation. Ref.20 Ref.25

VAR_007454

Experimental info

Mutagenesis

39

1

Y → F: No effect on osmotic stress-induced phosphorylation. Ref.20

Mutagenesis

67 – 71

5

Missing: Reduces polymerization into amyloid fibrils. Ref.22

Mutagenesis

71 – 82

12

Missing: Impairs polymerization into amyloid fibrils. Ref.22

Mutagenesis

76 – 77

2

Missing: Impairs polymerization into amyloid fibrils. Ref.22

Mutagenesis

76

1

Missing: Does not affect polymerization into amyloid fibrils.

Mutagenesis

77

1

Missing: Does not affect polymerization into amyloid fibrils. Ref.22

Mutagenesis

78

1

Missing: Does not affect polymerization into amyloid fibrils. Ref.22

Mutagenesis

85 – 94

10

Missing: Reduces polymerization into amyloid fibrils. Ref.22

Mutagenesis

125

1

Y → F: Abolishes osmotic stress-induced phosphorylation. Ref.20

Mutagenesis

133

1

Y → F: No effect on osmotic stress-induced phosphorylation. Ref.20

Mutagenesis

136

1

Y → F: No effect on osmotic stress-induced phosphorylation. Ref.20

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

140

Helix Strand Turn

Details...

Helix

3 – 37

35

Helix

45 – 92

48

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: 8248242] [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: 7601450] [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: 7802671] [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: 11156617] [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: 14702039] [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: 15489334] [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: 10617630] [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: 10852916] [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: 11162638] [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: 11821392] [Abstract] Cited for: INTERACTION WITH PHOSPHOLIPASE D.
[17]	"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: 12859192] [Abstract] Cited for: INTERACTION WITH HISTONES, SUBCELLULAR LOCATION.
[18]	"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: 12859200] [Abstract] Cited for: ROLE OF THE C-TERMINUS IN FIBRILLOGENESIS.
[19]	"Recent advances on alpha-synuclein cell biology: functions and dysfunctions." Alves da Costa C. Curr. Mol. Med. 3:17-24(2003) [PubMed: 12558071] [Abstract] Cited for: REVIEW.
[20]	"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: 12893833] [Abstract] Cited for: MUTAGENESIS OF TYR-39; TYR-125; TYR-133 AND TYR-136, CHARACTERIZATION OF VARIANT THR-53, PHOSPHORYLATION AT TYR-125.
[21]	"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: 15282274] [Abstract] Cited for: SUBCELLULAR LOCATION.
[22]	"Characterization of hydrophobic residue requirements for alpha-synuclein fibrillization." Waxman E.A., Mazzulli J.R., Giasson B.I. Biochemistry 48:9427-9436(2009) [PubMed: 19722699] [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.
[23]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]	"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: 15615727] [Abstract] Cited for: STRUCTURE BY NMR IN COMPLEX WITH DETERGENT MICELLES.
[25]	"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: 9197268] [Abstract] Cited for: VARIANT PARK1 THR-53.
[26]	"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: 9462735] [Abstract] Cited for: VARIANT PARK1 PRO-30.
[27]	"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: 14755719] [Abstract] Cited for: VARIANT PARK1/DLB LYS-46.
[28]	"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: 15498564] [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	[»]

ProteinModelPortal

P37840.

SMR

P37840. Positions 1-140.

DisProt

DP00070.

ModBase

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Protein-protein interaction databases

DIP

DIP-35354N.

IntAct

P37840. 187 interactions.

MINT

MINT-2515483.

STRING

P37840.

Protein family/group databases

TCDB

1.C.77.1.1. synuclein family.

PTM databases

PhosphoSite

P37840.

Polymorphism databases

DMDM

586067.

Proteomic databases

PRIDE

P37840.

Protocols and materials databases

StructuralBiologyKnowledgebase

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Genome annotation databases

Ensembl

ENST00000336904; ENSP00000338345; ENSG00000145335.
ENST00000394986; ENSP00000378437; ENSG00000145335.
ENST00000394991; ENSP00000378442; ENSG00000145335.

GeneID

6622.

KEGG

hsa:6622.

UCSC

uc003hso.1. human.
uc003hsp.1. human.
uc010ikt.1. human.

Organism-specific databases

CTD

6622.

GeneCards

GC04M090646.

H-InvDB

HIX0004376.

HGNC

HGNC:11138. SNCA.

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

prNOG21039.

HOGENOM

HBG715579.

HOVERGEN

HBG000481.

InParanoid

P37840.

OMA

PENEAYE.

PhylomeDB

P37840.

Enzyme and pathway databases

Pathway_Interaction_DB

alphasynuclein_pathway. Alpha-synuclein signaling.

Reactome

REACT_75925. Amyloids.

Gene expression databases

ArrayExpress

P37840.

Bgee

P37840.

CleanEx

HS_SNCA.

Genevestigator

P37840.

GermOnline

ENSG00000145335. Homo sapiens.

Family and domain databases

InterPro

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

Gene3D

G3DSA:1.10.287.700. Synuclein. 1 hit.

KO

K04528.

PANTHER

PTHR13820. Synuclein. 1 hit.

Pfam

PF01387. Synuclein. 1 hit.
[Graphical view]

PRINTS

PR01212. ASYNUCLEIN.
PR01211. SYNUCLEIN.

ProtoNet

Search...

Other

DrugBank

DB01065. Melatonin.

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:	January 25, 2012
This is version 143 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.