UniProtKB/Swiss-Prot O60260: Variant p.Arg275Trp

E3 ubiquitin-protein ligase parkin
Gene: PRKN
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Variant information Variant position:

275 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Arginine (R) to Tryptophan (W) at position 275 (R275W, p.Arg275Trp). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from large size and basic (R) to large size and aromatic (W) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

In PARK2 and PARK; impairs the ability to ubiquitinate SNCAIP; abolishes p53/TP53 transcriptional repression; impairs the ability to ubiquitinate and degrade SYT11. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs34424986 [ dbSNP | Ensembl ]

Sequence information Variant position:

275 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

465 The length of the canonical sequence.
Location on the sequence:

SRHVICLDCFHLYCVTRLND R QFVHDPQLGYSLPCVAGCPN The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         SRHVICLDCFHLYCVTRLNDRQFVHDPQLGYSLPCVAGCPN

Mouse                         HRHVICLDCFHLYCVTRLNDRQFVHDAQLGYSLPCVAGCPN

Rat                           HRHVICLDCFHLYCVTRLNDRQFVHDAQLGYSLPCVAGCPN

Drosophila                    SQHVTCIDCFRHYCRSRLGERQFMPHPDFGYTLPCPAGCEH

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 465	E3 ubiquitin-protein ligase parkin
Zinc finger	238 – 293	RING-type 1
Region	234 – 465	TRIAD supradomain
Region	257 – 293	SYT11 binding 2
Binding site	257 – 257
Binding site	260 – 260
Binding site	263 – 263
Binding site	289 – 289
Binding site	293 – 293
Alternative sequence	290 – 290	V -> VGTGDTVVLRGALGGFRRGV. In isoform 5.

Literature citations
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)
Cited for: FUNCTION; INTERACTION WITH SNCAIP; CHARACTERIZATION OF VARIANTS PARK2 ARG-240; CYS-256; TRP-275 AND ASN-415; MUTAGENESIS OF CYS-337; CYS-421 AND CYS-431; Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson's disease.
da Costa C.A.; Sunyach C.; Giaime E.; West A.; Corti O.; Brice A.; Safe S.; Abou-Sleiman P.M.; Wood N.W.; Takahashi H.; Goldberg M.S.; Shen J.; Checler F.;
Nat. Cell Biol. 11:1370-1375(2009)
Cited for: FUNCTION IN PROTECTION OF APOPTOSIS; CHARACTERIZATION OF VARIANTS PARK2 ASN-161; CYS-256; TRP-275; ARG-418 AND ARG-441; DOMAIN; PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson's disease.
Shin J.H.; Ko H.S.; Kang H.; Lee Y.; Lee Y.I.; Pletinkova O.; Troconso J.C.; Dawson V.L.; Dawson T.M.;
Cell 144:689-702(2011)
Cited for: FUNCTION; INTERACTION WITH ZNF746; CHARACTERIZATION OF VARIANTS PARK2 TRP-275; ASP-430 AND PHE-431; A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe.
Abbas N.; Luecking C.B.; Ricard S.; Duerr A.; Bonifati V.; De Michele G.; Bouley S.; Vaughan J.R.; Gasser T.; Marconi R.; Broussolle E.; Brefel-Courbon C.; Harhangi B.S.; Oostra B.A.; Fabrizio E.; Bohme G.A.; Pradier L.; Wood N.W.; Filla A.; Meco G.; Denefle P.; Agid Y.; Brice A.;
Hum. Mol. Genet. 8:567-574(1999)
Cited for: VARIANTS PARK2 ASN-161; CYS-256; TRP-275 AND ASN-415; VARIANTS ASN-167; LEU-380 AND ASN-394; Association between early-onset Parkinson's disease and mutations in the parkin gene.
Luecking C.B.; Duerr A.; Bonifati V.; Vaughan J.R.; De Michele G.; Gasser T.; Harhangi B.S.; Meco G.; Denefle P.; Wood N.W.; Agid Y.; Brice A.;
N. Engl. J. Med. 342:1560-1567(2000)
Cited for: VARIANTS PARK2 ASN-161; ASN-211; CYS-256; TRP-275; ASN-280; GLY-289; GLU-328; ASN-415 AND ASP-430; VARIANT CYS-334; Origin of the mutations in the parkin gene in Europe: exon rearrangements are independent recurrent events, whereas point mutations may result from founder effects.
Periquet M.; Luecking C.B.; Vaughan J.R.; Bonifati V.; Duerr A.; De Michele G.; Horstink M.; Farrer M.; Illarioshkin S.N.; Pollak P.; Borg M.; Brefel-Courbon C.; Denefle P.; Meco G.; Gasser T.; Breteler M.M.; Wood N.W.; Agid Y.; Brice A.;
Am. J. Hum. Genet. 68:617-626(2001)
Cited for: VARIANTS PARK2 ASN-211; TRP-275 AND ASP-430; Complex relationship between parkin mutations and Parkinson disease.
West A.; Periquet M.; Lincoln S.; Luecking C.B.; Nicholl D.; Bonifati V.; Rawal N.; Gasser T.; Lohmann E.; Deleuze J.-F.; Maraganore D.; Levey A.; Wood N.W.; Duerr A.; Hardy J.; Brice A.; Farrer M.;
Am. J. Med. Genet. 114:584-591(2002)
Cited for: VARIANTS PARK2 GLU-82; CYS-256; TRP-275; GLU-328 AND ARG-441; Linkage stratification and mutation analysis at the parkin locus identifies mutation positive Parkinson's disease families.
Nichols W.C.; Pankratz N.; Uniacke S.K.; Pauciulo M.W.; Halter C.; Rudolph A.; Conneally P.M.; Foroud T.;
J. Med. Genet. 39:489-492(2002)
Cited for: VARIANTS PARK2 ASN-211; TRP-275; ASP-430 AND LEU-437; Evaluation of 50 probands with early-onset Parkinson's disease for parkin mutations.
Hedrich K.; Marder K.; Harris J.; Kann M.; Lynch T.; Meija-Santana H.; Pramstaller P.P.; Schwinger E.; Bressman S.B.; Fahn S.; Klein C.;
Neurology 58:1239-1246(2002)
Cited for: VARIANTS PARK2 PRO-42; LEU-192; CYS-256; TRP-275; ASP-430 AND LEU-437; Parkin mutations and susceptibility alleles in late-onset Parkinson's disease.
Oliveira S.A.; Scott W.K.; Martin E.R.; Nance M.A.; Watts R.L.; Hubble J.P.; Koller W.C.; Pahwa R.; Stern M.B.; Hiner B.C.; Ondo W.G.; Allen F.H. Jr.; Scott B.L.; Goetz C.G.; Small G.W.; Mastaglia F.; Stajich J.M.; Zhang F.; Booze M.W.; Winn M.P.; Middleton L.T.; Haines J.L.; Pericak-Vance M.A.; Vance J.M.;
Ann. Neurol. 53:624-629(2003)
Cited for: VARIANTS PARK2 GLN-33; GLU-82; ASP-430 AND LEU-437; VARIANTS PARK TYR-253; CYS-256; TRP-275 AND ASN-280; VARIANTS LEU-380 AND ASN-394; Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease.
Kilarski L.L.; Pearson J.P.; Newsway V.; Majounie E.; Knipe M.D.; Misbahuddin A.; Chinnery P.F.; Burn D.J.; Clarke C.E.; Marion M.H.; Lewthwaite A.J.; Nicholl D.J.; Wood N.W.; Morrison K.E.; Williams-Gray C.H.; Evans J.R.; Sawcer S.J.; Barker R.A.; Wickremaratchi M.M.; Ben-Shlomo Y.; Williams N.M.; Morris H.R.;
Mov. Disord. 27:1522-1529(2012)
Cited for: VARIANT PARK2 TRP-275; Synaptotagmin-11 is a critical mediator of parkin-linked neurotoxicity and Parkinson's disease-like pathology.
Wang C.; Kang X.; Zhou L.; Chai Z.; Wu Q.; Huang R.; Xu H.; Hu M.; Sun X.; Sun S.; Li J.; Jiao R.; Zuo P.; Zheng L.; Yue Z.; Zhou Z.;
Nat. Commun. 9:81-81(2018)
Cited for: CHARACTERIZATION OF VARIANTS PARK PRO-42 AND TRP-275; FUNCTION;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.