Q9Y6H5 (SNCAP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Synphilin-1
Short name=Sph1

Alternative name(s):
Alpha-synuclein-interacting protein

Gene names

Name:

SNCAIP

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	919 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Isoform 2 inhibits the ubiquitin ligase activity of SIAH1 and inhibits proteasomal degradation of target proteins. Isoform 2 inhibits autoubiquitination and proteasomal degradation of SIAH1, and thereby increases cellular levels of SIAH. Isoform 2 modulates SNCA monoubiquitination by SIAH1. Ref.3 Ref.12
Subunit structure	Homodimer Probable. Heterodimer of isoform 1 and isoform 2 Probable. Interacts with SIAH1, SIAH2, SNCA, RNF19A AND PARK2. Isoform 2 has a strong tendency to form aggregates and can sequester isoform 1. Ref.1 Ref.3 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13
Subcellular location	Cytoplasm. Note: Detected in cytoplasmic inclusion bodies, together with SNCA. Ref.1 Ref.3 Ref.10 Ref.13
Tissue specificity	Detected in brain (at protein level). Widely expressed, with highest levels in brain, heart and placenta. Ref.1 Ref.3
Post-translational modification	Ubiquitinated; mediated by SIAH1, SIAH2 or RNF19A and leading to its subsequent proteasomal degradation. In the absence of proteasomal degradation, ubiquitinated SNCAIP accumulates in cytoplasmic inclusion bodies. Isoform 2 is subject to limited ubiquitination that does not lead to proteasomal degradation. Ref.7 Ref.8 Ref.9 Ref.10
Involvement in disease	Defects in SNCAIP may be a cause of Parkinson disease (PARK) [MIM:168600]. 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.7 Ref.14 Ref.15
Miscellaneous	Constructs encoding portions of SNCA and SNCAIP co-transfected in mammalian cells promote cytosolic inclusions resembling the Lewy bodies of Parkinson disease. Coexpression of SNCA, SNCAIP, and PARK2 result in the formation of Lewy body-like. ubiquitin-positive cytosolic inclusions. SNCAIP isoform 2 is particularly aggregatation-prone. Familial mutations in PARK2 disrupt the ubiquitination of SNCAIP and the formation of the ubiquitin-positive inclusions. These results provide a molecular basis for the ubiquitination of Lewy body-associated proteins and link PARK2 and SNCA in a common pathogenic mechanism through their interaction with SNCAIP.
Sequence similarities	Contains 6 ANK repeats.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Neurodegeneration Parkinson disease Parkinsonism
Domain	ANK repeat Coiled coil Repeat
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell death Inferred from electronic annotation. Source: UniProtKB-KW dopamine metabolic process Inferred from direct assay Ref.9. Source: MGI regulation of inclusion body assembly Inferred from direct assay. Source: BHF-UCL regulation of neurotransmitter secretion Inferred from direct assay Ref.9. Source: MGI
Cellular component	cytoplasm Inferred from direct assay Ref.9. Source: MGI neuronal cell body Non-traceable author statement. Source: UniProtKB nucleolus Inferred from direct assay. Source: HPA presynaptic membrane Non-traceable author statement. Source: UniProtKB
Molecular function	ubiquitin protein ligase binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y6H5-1)

Also known as: 1a;

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 (identifier: Q9Y6H5-2)

Also known as: Synphilin-1A;

The sequence of this isoform differs from the canonical sequence as follows:
     1-366: Missing.
     367-394: QHLTSLMGEDCLNERNTEKLTPAGLAIK → MTYLIQSHHSRRSQNCAEDVIRKTKTDQ
     919-919: A → EMYSSCINLSSNMLIEEHLCNDTRHNDINRKMKKSYSIKHIAEPESKELFL

Isoform 3 (identifier: Q9Y6H5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     19-19: S → SDNRSQGNRLQKLGLEDTDREDAMGFGSHRAKLTVVAALGACHCPENE
     919-919: A → EMYSSCINLSSNMLIEEHLCNDTRHNDINRKMKKSYSIKHIAEPESKELFL

Isoform 4 (identifier: Q9Y6H5-4)

Also known as: 1b;

The sequence of this isoform differs from the canonical sequence as follows:
     335-394: Missing.

Isoform 5 (identifier: Q9Y6H5-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-366: Missing.
     367-394: QHLTSLMGEDCLNERNTEKLTPAGLAIK → MTYLIQSHHSRRSQNCAEDVIRKTKTDQ

Isoform 6 (identifier: Q9Y6H5-6)

Also known as: 1c;

The sequence of this isoform differs from the canonical sequence as follows:
     19-19: S → SDNRSQGNRLQKLGLEDTDREDAMGFGSHRAKLTVVAALGACHCPENE
     476-541: LVEYGANVTM...QTVERVTLQN → RLKIQGTWNG...NQLPETKSSY
     542-919: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 919

919

Synphilin-1

PRO_0000067068

Regions

Repeat

349 – 380

32

ANK 1

Repeat

384 – 413

30

ANK 2

Repeat

419 – 448

30

ANK 3

Repeat

456 – 485

30

ANK 4

Repeat

603 – 632

30

ANK 5

Repeat

699 – 729

31

ANK 6

Coiled coil

515 – 552

38

Potential

Amino acid modifications

Modified residue

387

1

Phosphothreonine Ref.11

Natural variations

Alternative sequence

1 – 366

366

Missing in isoform 2 and isoform 5.

VSP_038839

Alternative sequence

19

1

S → SDNRSQGNRLQKLGLEDTDR EDAMGFGSHRAKLTVVAALG ACHCPENE in isoform 3 and isoform 6.

VSP_038840

Alternative sequence

335 – 394

60

Missing in isoform 4.

VSP_038841

Alternative sequence

367 – 394

28

QHLTS…GLAIK → MTYLIQSHHSRRSQNCAEDV IRKTKTDQ in isoform 2 and isoform 5.

VSP_038842

Alternative sequence

476 – 541

66

LVEYG…VTLQN → RLKIQGTWNGSETCLFTHHF SSYPPISSGLQCQGQEGVLF IPDQVGAATNKQVLFQNQLP ETKSSY in isoform 6.

VSP_038843

Alternative sequence

542 – 919

378

Missing in isoform 6.

VSP_038844

Alternative sequence

919

1

A → EMYSSCINLSSNMLIEEHLC NDTRHNDINRKMKKSYSIKH IAEPESKELFL in isoform 2 and isoform 3.

VSP_038845

Natural variant

44

1

V → A. Ref.1 Ref.4 Ref.15
Corresponds to variant rs56285021 [ dbSNP | Ensembl ].

VAR_065358

Natural variant

235

1

E → G.
Corresponds to variant rs6867105 [ dbSNP | Ensembl ].

VAR_048312

Natural variant

621

1

R → C Found in patients with symptoms of Parkinson disease; unknown pathological significance; reduced number of cytoplasmic inclusions in cells expressing C-621 compared with cells expressing wild-type (wt) protein when subjected to proteasomal inhibition; C-621 transfected cells are more susceptible to staurosporine-induced cell death than cells expressin wt protein. Ref.14 Ref.15
Corresponds to variant rs28937592 [ dbSNP | Ensembl ].

VAR_025667

Natural variant

706

1

E → Q. Ref.15

VAR_065359

Experimental info

Mutagenesis

79

1

V → N: Decreases interaction with SIAH1 and formation of cytoplasmic inclusion bodies; when associated with N-81. Ref.10

Mutagenesis

81

1

P → N: Decreases interaction with SIAH1 and formation of cytoplasmic inclusion bodies; when associated with N-79. Ref.10

Sequence conflict

188

1

S → F in AAH40552. Ref.6

Sequence conflict

614

1

E → G in AAH40552. Ref.6

Sequence conflict

696

1

A → G in AAH40552. Ref.6

Sequence conflict

712

1

D → G in AAH94759. Ref.6

Sequence conflict

801

1

S → P in AAH33743. Ref.6

Sequence conflict

919

1

A → E in AAH94759. Ref.6

Secondary structure

1

.

.

.

919

Helix Strand Turn

Details...

Helix

512 – 552

41

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (1a) [UniParc]. Last modified July 22, 2008. Version 2. Checksum: 55C5316F250D0480	FASTA	919	100,409
	10 20 30 40 50 60 MEAPEYLDLD EIDFSDDISY SVTSLKTIPE LCRRCDTQNE DRSVSSSSWN CGISTLITNT 70 80 90 100 110 120 QKPTGIADVY SKFRPVKRVS PLKHQPETLE NNESDDQKNQ KVVEYQKGGE SDLGPQPQEL 130 140 150 160 170 180 GPGDGVGGPP GKSSEPSTSL GELEHYDLDM DEILDVPYIK SSQQLASFTK VTSEKRILGL 190 200 210 220 230 240 CTTINGLSGK ACSTGSSESS SSNMAPFCVL SPVKSPHLRK ASAVIHDQHK LSTEETEISP 250 260 270 280 290 300 PLVKCGSAYE PENQSKDFLN KTFSDPHGRK VEKTTPDCQL RAFHLQSSAA ESKPEEQVSG 310 320 330 340 350 360 LNRTSSQGPE ERSEYLKKVK SILNIVKEGQ ISLLPHLAAD NLDKIHDENG NNLLHIAASQ 370 380 390 400 410 420 GHAECLQHLT SLMGEDCLNE RNTEKLTPAG LAIKNGQLEC VRWMVSETEA IAELSCSKDF 430 440 450 460 470 480 PSLIHYAGCY GQEKILLWLL QFMQEQGISL DEVDQDGNSA VHVASQHGYL GCIQTLVEYG 490 500 510 520 530 540 ANVTMQNHAG EKPSQSAERQ GHTLCSRYLV VVETCMSLAS QVVKLTKQLK EQTVERVTLQ 550 560 570 580 590 600 NQLQQFLEAQ KSEGKSLPSS PSSPSSPASR KSQWKSPDAD DDSVAKSKPG VQEGIQVLGS 610 620 630 640 650 660 LSASSRARPK AKDEDSDKIL RQLLGKEISE NVCTQEKLSL EFQDAQASSR NSKKIPLEKR 670 680 690 700 710 720 ELKLARLRQL MQRSLSESDT DSNNSEDPKT TPVRKADRPR PQPIVESVES MDSAESLHLM 730 740 750 760 770 780 IKKHTLASGG RRFPFSIKAS KSLDGHSPSP TSESSEPDLE SQYPGSGSIP PNQPSGDPQQ 790 800 810 820 830 840 PSPDSTAAQK VATSPKSALK SPSSKRRTSQ NLKLRVTFEE PVVQMEQPSL ELNGEKDKDK 850 860 870 880 890 900 GRTLQRTSTS NESGDQLKRP FGAFRSIMET LSGNQNNNNN YQAANQLKTS TLPLTSLGRK 910 TDAKGNPASS ASKGKNKAA
	Isoform 2 (Synphilin-1A) [UniParc]. Checksum: 3C41F69D861CE493	FASTA	603	66,646
	10 20 30 40 50 60 MTYLIQSHHS RRSQNCAEDV IRKTKTDQNG QLECVRWMVS ETEAIAELSC SKDFPSLIHY 70 80 90 100 110 120 AGCYGQEKIL LWLLQFMQEQ GISLDEVDQD GNSAVHVASQ HGYLGCIQTL VEYGANVTMQ 130 140 150 160 170 180 NHAGEKPSQS AERQGHTLCS RYLVVVETCM SLASQVVKLT KQLKEQTVER VTLQNQLQQF 190 200 210 220 230 240 LEAQKSEGKS LPSSPSSPSS PASRKSQWKS PDADDDSVAK SKPGVQEGIQ VLGSLSASSR 250 260 270 280 290 300 ARPKAKDEDS DKILRQLLGK EISENVCTQE KLSLEFQDAQ ASSRNSKKIP LEKRELKLAR 310 320 330 340 350 360 LRQLMQRSLS ESDTDSNNSE DPKTTPVRKA DRPRPQPIVE SVESMDSAES LHLMIKKHTL 370 380 390 400 410 420 ASGGRRFPFS IKASKSLDGH SPSPTSESSE PDLESQYPGS GSIPPNQPSG DPQQPSPDST 430 440 450 460 470 480 AAQKVATSPK SALKSPSSKR RTSQNLKLRV TFEEPVVQME QPSLELNGEK DKDKGRTLQR 490 500 510 520 530 540 TSTSNESGDQ LKRPFGAFRS IMETLSGNQN NNNNYQAANQ LKTSTLPLTS LGRKTDAKGN 550 560 570 580 590 600 PASSASKGKN KAEMYSSCIN LSSNMLIEEH LCNDTRHNDI NRKMKKSYSI KHIAEPESKE LFL
	Isoform 3 [UniParc]. Checksum: 6EC840B66BA8217D	FASTA	1,016	111,455
	10 20 30 40 50 60 MEAPEYLDLD EIDFSDDISD NRSQGNRLQK LGLEDTDRED AMGFGSHRAK LTVVAALGAC 70 80 90 100 110 120 HCPENEYSVT SLKTIPELCR RCDTQNEDRS VSSSSWNCGI STLITNTQKP TGIADVYSKF 130 140 150 160 170 180 RPVKRVSPLK HQPETLENNE SDDQKNQKVV EYQKGGESDL GPQPQELGPG DGVGGPPGKS 190 200 210 220 230 240 SEPSTSLGEL EHYDLDMDEI LDVPYIKSSQ QLASFTKVTS EKRILGLCTT INGLSGKACS 250 260 270 280 290 300 TGSSESSSSN MAPFCVLSPV KSPHLRKASA VIHDQHKLST EETEISPPLV KCGSAYEPEN 310 320 330 340 350 360 QSKDFLNKTF SDPHGRKVEK TTPDCQLRAF HLQSSAAESK PEEQVSGLNR TSSQGPEERS 370 380 390 400 410 420 EYLKKVKSIL NIVKEGQISL LPHLAADNLD KIHDENGNNL LHIAASQGHA ECLQHLTSLM 430 440 450 460 470 480 GEDCLNERNT EKLTPAGLAI KNGQLECVRW MVSETEAIAE LSCSKDFPSL IHYAGCYGQE 490 500 510 520 530 540 KILLWLLQFM QEQGISLDEV DQDGNSAVHV ASQHGYLGCI QTLVEYGANV TMQNHAGEKP 550 560 570 580 590 600 SQSAERQGHT LCSRYLVVVE TCMSLASQVV KLTKQLKEQT VERVTLQNQL QQFLEAQKSE 610 620 630 640 650 660 GKSLPSSPSS PSSPASRKSQ WKSPDADDDS VAKSKPGVQE GIQVLGSLSA SSRARPKAKD 670 680 690 700 710 720 EDSDKILRQL LGKEISENVC TQEKLSLEFQ DAQASSRNSK KIPLEKRELK LARLRQLMQR 730 740 750 760 770 780 SLSESDTDSN NSEDPKTTPV RKADRPRPQP IVESVESMDS AESLHLMIKK HTLASGGRRF 790 800 810 820 830 840 PFSIKASKSL DGHSPSPTSE SSEPDLESQY PGSGSIPPNQ PSGDPQQPSP DSTAAQKVAT 850 860 870 880 890 900 SPKSALKSPS SKRRTSQNLK LRVTFEEPVV QMEQPSLELN GEKDKDKGRT LQRTSTSNES 910 920 930 940 950 960 GDQLKRPFGA FRSIMETLSG NQNNNNNYQA ANQLKTSTLP LTSLGRKTDA KGNPASSASK 970 980 990 1000 1010 GKNKAEMYSS CINLSSNMLI EEHLCNDTRH NDINRKMKKS YSIKHIAEPE SKELFL
	Isoform 4 (1b) [UniParc]. Checksum: 949D53FF98FCE6E6	FASTA	859	93,930
	10 20 30 40 50 60 MEAPEYLDLD EIDFSDDISY SVTSLKTIPE LCRRCDTQNE DRSVSSSSWN CGISTLITNT 70 80 90 100 110 120 QKPTGIADVY SKFRPVKRVS PLKHQPETLE NNESDDQKNQ KVVEYQKGGE SDLGPQPQEL 130 140 150 160 170 180 GPGDGVGGPP GKSSEPSTSL GELEHYDLDM DEILDVPYIK SSQQLASFTK VTSEKRILGL 190 200 210 220 230 240 CTTINGLSGK ACSTGSSESS SSNMAPFCVL SPVKSPHLRK ASAVIHDQHK LSTEETEISP 250 260 270 280 290 300 PLVKCGSAYE PENQSKDFLN KTFSDPHGRK VEKTTPDCQL RAFHLQSSAA ESKPEEQVSG 310 320 330 340 350 360 LNRTSSQGPE ERSEYLKKVK SILNIVKEGQ ISLLNGQLEC VRWMVSETEA IAELSCSKDF 370 380 390 400 410 420 PSLIHYAGCY GQEKILLWLL QFMQEQGISL DEVDQDGNSA VHVASQHGYL GCIQTLVEYG 430 440 450 460 470 480 ANVTMQNHAG EKPSQSAERQ GHTLCSRYLV VVETCMSLAS QVVKLTKQLK EQTVERVTLQ 490 500 510 520 530 540 NQLQQFLEAQ KSEGKSLPSS PSSPSSPASR KSQWKSPDAD DDSVAKSKPG VQEGIQVLGS 550 560 570 580 590 600 LSASSRARPK AKDEDSDKIL RQLLGKEISE NVCTQEKLSL EFQDAQASSR NSKKIPLEKR 610 620 630 640 650 660 ELKLARLRQL MQRSLSESDT DSNNSEDPKT TPVRKADRPR PQPIVESVES MDSAESLHLM 670 680 690 700 710 720 IKKHTLASGG RRFPFSIKAS KSLDGHSPSP TSESSEPDLE SQYPGSGSIP PNQPSGDPQQ 730 740 750 760 770 780 PSPDSTAAQK VATSPKSALK SPSSKRRTSQ NLKLRVTFEE PVVQMEQPSL ELNGEKDKDK 790 800 810 820 830 840 GRTLQRTSTS NESGDQLKRP FGAFRSIMET LSGNQNNNNN YQAANQLKTS TLPLTSLGRK 850 TDAKGNPASS ASKGKNKAA
	Isoform 5 [UniParc]. Checksum: EAEBC23FCD35545A	FASTA	553	60,693
	10 20 30 40 50 60 MTYLIQSHHS RRSQNCAEDV IRKTKTDQNG QLECVRWMVS ETEAIAELSC SKDFPSLIHY 70 80 90 100 110 120 AGCYGQEKIL LWLLQFMQEQ GISLDEVDQD GNSAVHVASQ HGYLGCIQTL VEYGANVTMQ 130 140 150 160 170 180 NHAGEKPSQS AERQGHTLCS RYLVVVETCM SLASQVVKLT KQLKEQTVER VTLQNQLQQF 190 200 210 220 230 240 LEAQKSEGKS LPSSPSSPSS PASRKSQWKS PDADDDSVAK SKPGVQEGIQ VLGSLSASSR 250 260 270 280 290 300 ARPKAKDEDS DKILRQLLGK EISENVCTQE KLSLEFQDAQ ASSRNSKKIP LEKRELKLAR 310 320 330 340 350 360 LRQLMQRSLS ESDTDSNNSE DPKTTPVRKA DRPRPQPIVE SVESMDSAES LHLMIKKHTL 370 380 390 400 410 420 ASGGRRFPFS IKASKSLDGH SPSPTSESSE PDLESQYPGS GSIPPNQPSG DPQQPSPDST 430 440 450 460 470 480 AAQKVATSPK SALKSPSSKR RTSQNLKLRV TFEEPVVQME QPSLELNGEK DKDKGRTLQR 490 500 510 520 530 540 TSTSNESGDQ LKRPFGAFRS IMETLSGNQN NNNNYQAANQ LKTSTLPLTS LGRKTDAKGN 550 PASSASKGKN KAA
	Isoform 6 (1c) [UniParc]. Checksum: EBF343E479576255	FASTA	588	64,469
	10 20 30 40 50 60 MEAPEYLDLD EIDFSDDISD NRSQGNRLQK LGLEDTDRED AMGFGSHRAK LTVVAALGAC 70 80 90 100 110 120 HCPENEYSVT SLKTIPELCR RCDTQNEDRS VSSSSWNCGI STLITNTQKP TGIADVYSKF 130 140 150 160 170 180 RPVKRVSPLK HQPETLENNE SDDQKNQKVV EYQKGGESDL GPQPQELGPG DGVGGPPGKS 190 200 210 220 230 240 SEPSTSLGEL EHYDLDMDEI LDVPYIKSSQ QLASFTKVTS EKRILGLCTT INGLSGKACS 250 260 270 280 290 300 TGSSESSSSN MAPFCVLSPV KSPHLRKASA VIHDQHKLST EETEISPPLV KCGSAYEPEN 310 320 330 340 350 360 QSKDFLNKTF SDPHGRKVEK TTPDCQLRAF HLQSSAAESK PEEQVSGLNR TSSQGPEERS 370 380 390 400 410 420 EYLKKVKSIL NIVKEGQISL LPHLAADNLD KIHDENGNNL LHIAASQGHA ECLQHLTSLM 430 440 450 460 470 480 GEDCLNERNT EKLTPAGLAI KNGQLECVRW MVSETEAIAE LSCSKDFPSL IHYAGCYGQE 490 500 510 520 530 540 KILLWLLQFM QEQGISLDEV DQDGNSAVHV ASQHGYLGCI QTRLKIQGTW NGSETCLFTH 550 560 570 580 HFSSYPPISS GLQCQGQEGV LFIPDQVGAA TNKQVLFQNQ LPETKSSY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Synphilin-1 associates with alpha-synuclein and promotes the formation of cytosolic inclusions." Engelender S., Kaminsky Z., Guo X., Sharp A.H., Amaravi R.K., Kleiderlein J.J., Margolis R.L., Troncoso J.C., Lanahan A., Worley P.F., Dawson V.L., Dawson T.M., Ross C.A. Nat. Genet. 22:110-114(1999) [PubMed: 10319874] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH SNCA, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT ALA-44. Tissue: Brain.
[2]	"Organization of the human synphilin-1 gene, a candidate for Parkinson's disease." Engelender S., Wanner T., Kleiderlein J.J., Wakabayashi K., Tsuji S., Takahashi H., Ashworth R., Margolis R.L., Ross C.A. Mamm. Genome 11:763-766(2000) [PubMed: 10967135] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[3]	"Synphilin-1A: an aggregation-prone isoform of synphilin-1 that causes neuronal death and is present in aggregates from alpha-synucleinopathy patients." Eyal A., Szargel R., Avraham E., Liani E., Haskin J., Rott R., Engelender S. Proc. Natl. Acad. Sci. U.S.A. 103:5917-5922(2006) [PubMed: 16595633] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH SNCA, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]	"Identification and characterization of alternatively spliced form of human synphilin-1." Lim M.K., Ohsawa Y., Kawamura T., Asakawa S., Takayanagi A., Minoshima S., Shimizu N. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 4 AND 6), VARIANT ALA-44. Tissue: Cerebellum and Testis.
[5]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORMS 2; 3 AND 5). Tissue: Brain and Testis.
[7]	"Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease." Chung K.K.K., Zhang Y., Lim K.L., Tanaka Y., Huang H., Gao J., Ross C.A., Dawson V.L., Dawson T.M. Nat. Med. 7:1144-1150(2001) [PubMed: 11590439] [Abstract] Cited for: INTERACTION WITH PARK2, UBIQUITINATION.
[8]	"Dorfin localizes to Lewy bodies and ubiquitylates synphilin-1." Ito T., Niwa J., Hishikawa N., Ishigaki S., Doyu M., Sobue G. J. Biol. Chem. 278:29106-29114(2003) [PubMed: 12750386] [Abstract] Cited for: INTERACTION WITH RNF19A, UBIQUITINATION.
[9]	"Siah-1 facilitates ubiquitination and degradation of synphilin-1." Nagano Y., Yamashita H., Takahashi T., Kishida S., Nakamura T., Iseki E., Hattori N., Mizuno Y., Kikuchi A., Matsumoto M. J. Biol. Chem. 278:51504-51514(2003) [PubMed: 14506261] [Abstract] Cited for: INTERACTION WITH SIAH1, DEGRADATION.
[10]	"Ubiquitylation of synphilin-1 and alpha-synuclein by SIAH and its presence in cellular inclusions and Lewy bodies imply a role in Parkinson's disease." Liani E., Eyal A., Avraham E., Shemer R., Szargel R., Berg D., Bornemann A., Riess O., Ross C.A., Rott R., Engelender S. Proc. Natl. Acad. Sci. U.S.A. 101:5500-5505(2004) [PubMed: 15064394] [Abstract] Cited for: SUBCELLULAR LOCATION, UBIQUITINATION, PROTEASOMAL DEGRADATION, INTERACTION WITH SIAH1 AND SIAH2, MUTAGENESIS OF VAL-79 AND PRO-81.
[11]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-387, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Synphilin-1A inhibits seven in absentia homolog (SIAH) and modulates alpha-synuclein monoubiquitylation and inclusion formation." Szargel R., Rott R., Eyal A., Haskin J., Shani V., Balan L., Wolosker H., Engelender S. J. Biol. Chem. 284:11706-11716(2009) [PubMed: 19224863] [Abstract] Cited for: FUNCTION, INTERACTION WITH SIAH1.
[13]	"Interaction with synphilin-1 promotes inclusion formation of alpha-synuclein: mechanistic insights and pathological implication." Xie Y.Y., Zhou C.J., Zhou Z.R., Hong J., Che M.X., Fu Q.S., Song A.X., Lin D.H., Hu H.Y. FASEB J. 24:196-205(2010) [PubMed: 19762560] [Abstract] Cited for: STRUCTURE BY NMR OF 512-557, INTERACTION WITH SNCA, PROMOTION OF INCLUSION BODY FORMATION, SUBCELLULAR LOCATION.
[14]	"Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson's disease." Marx F.P., Holzmann C., Strauss K.M., Li L., Eberhardt O., Gerhardt E., Cookson M.R., Hernandez D., Farrer M.J., Kachergus J., Engelender S., Ross C.A., Berger K., Schols L., Schulz J.B., Riess O., Kruger R. Hum. Mol. Genet. 12:1223-1231(2003) [PubMed: 12761037] [Abstract] Cited for: VARIANT CYS-621, CHARACTERIZATION OF VARIANT CYS-621, POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY TO PARKINSON DISEASE.
[15]	"Genetic association study of synphilin-1 in idiopathic Parkinson's disease." Myhre R., Klungland H., Farrer M.J., Aasly J.O. BMC Med. Genet. 9:19-19(2008) [PubMed: 18366718] [Abstract] Cited for: VARIANTS ALA-44; CYS-621 AND GLN-706, LACK OF ASSOCIATION WITH PARKINSON DISEASE.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF076929 mRNA. Translation: AAD30362.1.
AF167306 , AF167301, AF167302, AF167303, AF167304, AF167305 Genomic DNA. Translation: AAG17478.1.
DQ227317 mRNA. Translation: ABB51162.1.
CH471086 Genomic DNA. Translation: EAW48889.1.
AB110788 mRNA. Translation: BAD19017.1.
AB110789 mRNA. Translation: BAD19018.1.
AB110790 mRNA. Translation: BAD19019.1.
CH471086 Genomic DNA. Translation: EAW48890.1.
BC033743 mRNA. Translation: AAH33743.1.
BC040552 mRNA. Translation: AAH40552.1.
BC094759 mRNA. Translation: AAH94759.1.

IPI

IPI00002293.
IPI00385910.
IPI00438113.
IPI00956081.
IPI00956102.
IPI00967042.

RefSeq

NP_001229864.1. NM_001242935.1.
NP_005451.2. NM_005460.2.

UniGene

Hs.426463.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KES	NMR	-	A	512-557	[»]

ProteinModelPortal

Q9Y6H5.

SMR

Q9Y6H5. Positions 280-557.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y6H5. 6 interactions.

MINT

MINT-1380209.

STRING

Q9Y6H5.

PTM databases

PhosphoSite

Q9Y6H5.

Polymorphism databases

DMDM

205831000.

Proteomic databases

PRIDE

Q9Y6H5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000261367; ENSP00000261367; ENSG00000064692.
ENST00000261368; ENSP00000261368; ENSG00000064692.
ENST00000379533; ENSP00000368848; ENSG00000064692.
ENST00000379536; ENSP00000368851; ENSG00000064692.
ENST00000395469; ENSP00000378852; ENSG00000064692.
ENST00000503116; ENSP00000423199; ENSG00000064692.

GeneID

9627.

KEGG

hsa:9627.

Organism-specific databases

CTD

9627.

GeneCards

GC05P121675.

HGNC

HGNC:11139. SNCAIP.

HPA

HPA003266.

MIM

168600. phenotype.
603779. gene.

neXtProt

NX_Q9Y6H5.

PharmGKB

PA35987.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00390000001485.

HOVERGEN

HBG061375.

OMA

PIVESVE.

PhylomeDB

Q9Y6H5.

Gene expression databases

ArrayExpress

Q9Y6H5.

Bgee

Q9Y6H5.

CleanEx

HS_SNCAIP.

Genevestigator

Q9Y6H5.

GermOnline

ENSG00000064692. Homo sapiens.

Family and domain databases

InterPro

IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]

Gene3D

G3DSA:1.25.40.20. ANK. 1 hit.

KO

K04558.

Pfam

PF12796. Ank_2. 2 hits.
[Graphical view]

SMART

SM00248. ANK. 4 hits.
[Graphical view]

SUPFAM

SSF48403. ANK. 1 hit.

PROSITE

PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

36127.

PMAP-CutDB

Q9Y6H5.

SOURCE

Search...

Entry information

Entry name

SNCAP_HUMAN

Accession

Primary (citable) accession number: Q9Y6H5
Secondary accession number(s): D3DSZ1 , Q05BS1, Q1PSC2, Q49AC6, Q504U9, Q6L984, Q6L985, Q6L986, Q9HC59

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	July 22, 2008
Last modified:	January 25, 2012
This is version 103 of the entry and version 2 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.