UniProtKB/Swiss-Prot O60260: Variant p.Arg256Cys

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

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

US 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 Cysteine (C) at position 256 (R256C, p.Arg256Cys). 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 medium size and polar (C) 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; uncertain significance; impairs the ability to ubiquitinate SNCAIP and ZNF746; decreased binding to the TP53 promoter; abolishes TP53 transcriptional repression. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs150562946 [ dbSNP | Ensembl ]

Sequence information Variant position:

256 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:

ITCITCTDVRSPVLVFQCNS R HVICLDCFHLYCVTRLNDRQ 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                         ITCITCTDVRSPVLVFQCNSRHVICLDCFHLYCVTRLNDRQ

Mouse                         IPCIACTDVRSPVLVFQCNHRHVICLDCFHLYCVTRLNDRQ

Rat                           IPCIACTDVRNPVLVFQCNHRHVICLDCFHLYCVTRLNDRQ

Drosophila                    VPCLACTDVSDTVLVFPCASQHVTCIDCFRHYCRSRLGERQ

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
Binding site	238 – 238
Binding site	241 – 241
Binding site	253 – 253
Binding site	257 – 257
Binding site	260 – 260
Binding site	263 – 263
Mutagenesis	238 – 238	C -> S. Loss of mitochondrial localization.

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; 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; 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; 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;

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.