UniProtKB/Swiss-Prot O60260: Variant p.Arg334Cys

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

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

LB/B 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 334 (R334C, p.Arg334Cys). 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
Other resources:

Links to websites of interest for the variant.

Variant rs199657839 [ dbSNP | Ensembl ]

Sequence information Variant position:

334 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:

RYQQYGAEECVLQMGGVLCP R PGCGAGLLPEPDQRKVTCEG 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                         RYQQYGAEECVLQMGGVLCPRPGCGAGLLPEPDQRKVTCEG

Mouse                         RYQQYGAEECVLQMGGVLCPRPGCGAGLLPEQGQRKVTCEG

Rat                           RYQQYGAEECVLQMGGVLCPRPGCGAGLLPEQGQKKVTCEG

Drosophila                    RYQRFATEEYVLQAGGVLCPQPGCGMGLLVEPDCRKVTCQN

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	313 – 377	IBR-type
Region	234 – 465	TRIAD supradomain
Binding site	332 – 332
Binding site	337 – 337
Binding site	352 – 352
Cross	349 – 349	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)
Alternative sequence	298 – 465	Missing. In isoform 3.
Alternative sequence	312 – 361	Missing. In isoform 7 and isoform 8.
Mutagenesis	332 – 332	C -> S. Impairs folding of IBR domain.
Mutagenesis	337 – 337	C -> A. Impairs the ability to ubiquitinate SNCAIP.

Literature citations
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; Analysis of protein-coding genetic variation in 60,706 humans.
Lek M.; Karczewski K.J.; Minikel E.V.; Samocha K.E.; Banks E.; Fennell T.; O'Donnell-Luria A.H.; Ware J.S.; Hill A.J.; Cummings B.B.; Tukiainen T.; Birnbaum D.P.; Kosmicki J.A.; Duncan L.E.; Estrada K.; Zhao F.; Zou J.; Pierce-Hoffman E.; Berghout J.; Cooper D.N.; Deflaux N.; DePristo M.; Do R.; Flannick J.; Fromer M.; Gauthier L.; Goldstein J.; Gupta N.; Howrigan D.; Kiezun A.; Kurki M.I.; Moonshine A.L.; Natarajan P.; Orozco L.; Peloso G.M.; Poplin R.; Rivas M.A.; Ruano-Rubio V.; Rose S.A.; Ruderfer D.M.; Shakir K.; Stenson P.D.; Stevens C.; Thomas B.P.; Tiao G.; Tusie-Luna M.T.; Weisburd B.; Won H.H.; Yu D.; Altshuler D.M.; Ardissino D.; Boehnke M.; Danesh J.; Donnelly S.; Elosua R.; Florez J.C.; Gabriel S.B.; Getz G.; Glatt S.J.; Hultman C.M.; Kathiresan S.; Laakso M.; McCarroll S.; McCarthy M.I.; McGovern D.; McPherson R.; Neale B.M.; Palotie A.; Purcell S.M.; Saleheen D.; Scharf J.M.; Sklar P.; Sullivan P.F.; Tuomilehto J.; Tsuang M.T.; Watkins H.C.; Wilson J.G.; Daly M.J.; MacArthur D.G.;
Nature 536:285-291(2016)
Cited for: VARIANT CYS-334;

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.