2kes
From Proteopedia
Contents |
Solution Structure of the Coiled-coil Domain of Synphilin-1
Template:ABSTRACT PUBMED 19762560
Disease
[SNCAP_HUMAN] 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.[1][2][3]
Function
[SNCAP_HUMAN] 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.[4][5]
About this Structure
2kes is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA.
Reference
- Xie YY, Zhou CJ, Zhou ZR, Hong J, Che MX, Fu QS, Song AX, Lin DH, Hu HY. Interaction with synphilin-1 promotes inclusion formation of alpha-synuclein: mechanistic insights and pathological implication. FASEB J. 2010 Jan;24(1):196-205. Epub 2009 Sep 17. PMID:19762560 doi:10.1096/fj.09-133082
- ↑ Chung KK, Zhang Y, Lim KL, Tanaka Y, Huang H, Gao J, Ross CA, Dawson VL, Dawson TM. Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease. Nat Med. 2001 Oct;7(10):1144-50. PMID:11590439 doi:10.1038/nm1001-1144
- ↑ Marx FP, Holzmann C, Strauss KM, Li L, Eberhardt O, Gerhardt E, Cookson MR, Hernandez D, Farrer MJ, Kachergus J, Engelender S, Ross CA, Berger K, Schols L, Schulz JB, Riess O, Kruger R. Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson's disease. Hum Mol Genet. 2003 Jun 1;12(11):1223-31. PMID:12761037
- ↑ Myhre R, Klungland H, Farrer MJ, Aasly JO. Genetic association study of synphilin-1 in idiopathic Parkinson's disease. BMC Med Genet. 2008 Mar 21;9:19. doi: 10.1186/1471-2350-9-19. PMID:18366718 doi:10.1186/1471-2350-9-19
- ↑ Eyal A, Szargel R, Avraham E, Liani E, Haskin J, Rott R, Engelender S. Synphilin-1A: an aggregation-prone isoform of synphilin-1 that causes neuronal death and is present in aggregates from alpha-synucleinopathy patients. Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5917-22. Epub 2006 Apr 4. PMID:16595633 doi:10.1073/pnas.0509707103
- ↑ Szargel R, Rott R, Eyal A, Haskin J, Shani V, Balan L, Wolosker H, Engelender S. Synphilin-1A inhibits seven in absentia homolog (SIAH) and modulates alpha-synuclein monoubiquitylation and inclusion formation. J Biol Chem. 2009 Apr 24;284(17):11706-16. doi: 10.1074/jbc.M805990200. Epub 2009, Feb 17. PMID:19224863 doi:10.1074/jbc.M805990200