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UniProtKB/Swiss-Prot O60260: Variant p.Thr240Arg

E3 ubiquitin-protein ligase parkin
Gene: PRKN
Variant information

Variant position:  240
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 Threonine (T) to Arginine (R) at position 240 (T240R, p.Thr240Arg).
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 medium size and polar (T) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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; impairs the ability to ubiquitinate SNCAIP and BCL2; loss of UBE2L3 binding; severely compromises the mitochondrial localization.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  240
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:   KETSVALHLIATNSRNITCI  T CTDVRSPVLVFQCNSRHVIC
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                         KETSVALHLIATNSRNITCITCTDVRSPVLVFQCNSRHVIC

Mouse                         KDTSVALNLITSNRRSIPCIACTDVRSPVLVFQCNHRHVIC

Rat                           KDTSVALNLITNNSRSIPCIACTDVRNPVLVFQCNHRHVIC

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.

TypePositionsDescription
Chain 1 – 465 E3 ubiquitin-protein ligase parkin
Zinc finger 238 – 293 RING-type 1
Region 234 – 465 TRIAD supradomain
Metal binding 238 – 238 Zinc 1
Metal binding 241 – 241 Zinc 1
Metal binding 253 – 253 Zinc 2
Metal binding 257 – 257 Zinc 2; via pros nitrogen
Metal binding 260 – 260 Zinc 1
Mutagenesis 238 – 238 C -> S. Loss of mitochondrial localization.
Turn 239 – 241


Literature citations

Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase.
Shimura H.; Hattori N.; Kubo S.; Mizuno Y.; Asakawa S.; Minoshima S.; Shimizu N.; Iwai K.; Chiba T.; Tanaka K.; Suzuki T.;
Nat. Genet. 25:302-305(2000)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS PARK2 PRO-42 AND ARG-240;

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;

Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease.
Shimura H.; Schlossmacher M.G.; Hattori N.; Frosch M.P.; Trockenbacher A.; Schneider R.; Mizuno Y.; Kosik K.S.; Selkoe D.J.;
Science 293:263-269(2001)
Cited for: FUNCTION; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS PARK2 PRO-42 AND ARG-240;

Parkin mono-ubiquitinates Bcl-2 and regulates autophagy.
Chen D.; Gao F.; Li B.; Wang H.; Xu Y.; Zhu C.; Wang G.;
J. Biol. Chem. 285:38214-38223(2010)
Cited for: FUNCTION; INTERACTION WITH BCL2; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS PARK2 ASN-161; ARG-240; PHE-431 AND LEU-437;

Point mutations (Thr240Arg and Gln311Stop) in the Parkin gene.
Hattori N.; Matsumine H.; Asakawa S.; Kitada T.; Yoshino H.; Elibol B.; Brookes A.J.; Yamamura Y.; Kobayashi T.; Wang M.; Yoritaka A.; Minoshima S.; Shimizu N.; Mizuno Y.;
Biochem. Biophys. Res. Commun. 249:754-758(1998)
Cited for: VARIANT PARK2 ARG-240;

PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy.
Matsuda N.; Sato S.; Shiba K.; Okatsu K.; Saisho K.; Gautier C.A.; Sou Y.S.; Saiki S.; Kawajiri S.; Sato F.; Kimura M.; Komatsu M.; Hattori N.; Tanaka K.;
J. Cell Biol. 189:211-221(2010)
Cited for: CHARACTERIZATION OF VARIANTS PARK2 ASN-161; ASN-211; ARG-240; ASN-280 AND GLU-328;

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.