UniProtKB/Swiss-Prot O60260: Variant p.Met192Val

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

192 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 Methionine (M) to Valine (V) at position 192 (M192V, p.Met192Val). 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:

Similar physico-chemical property. Both residues are medium size and hydrophobic. 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; uncertain significance. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs9456735 [ dbSNP | Ensembl ]

Sequence information Variant position:

192 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:

ATLTLTQGPSCWDDVLIPNR M SGECQSPHCPGTSAEFFFKC 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                         ATLTLTQGPSCWDDVLIPNRMSGECQSPHCPGTS--------AEFFFKC

Mouse                         ATLTLAQGPSCWDDVLIPNRMSGECQSPDCPGTR-------

Rat                           ATLTLAQGPSCWDDVLIPNRMSGECQSPDCPGTR-------

Drosophila                    GAFTVHRDPECWDDVLKSRRIPGHCESLEVACVDNAAGDPP

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	141 – 225	RING-type 0; atypical
Region	77 – 237	Necessary for PINK1-dependent localization to mitochondria
Modified residue	175 – 175	Phosphothreonine; by PINK1
Alternative sequence	58 – 206	Missing. In isoform 6.
Alternative sequence	179 – 206	Missing. In isoform 2 and isoform 7.
Mutagenesis	175 – 175	T -> A. Loss of phosphorylation. Reduced mitochondrial localization; when associated with A-217.
Mutagenesis	175 – 175	T -> E. Phosphomimetic mutant. Mostly localizes to the mitochondria; when associated with E-217.
Mutagenesis	211 – 211	K -> N. Loss of activity towards MIRO1.
Beta strand	192 – 196

Literature citations
Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease.
Foroud T.; Uniacke S.K.; Liu L.; Pankratz N.; Rudolph A.; Halter C.; Shults C.; Marder K.; Conneally P.M.; Nichols W.C.;
Neurology 60:796-801(2003)
Cited for: VARIANTS PARK2 VAL-192; ASN-211; MET-240 AND LEU-437; VARIANT ASN-167; INVOLVEMENT IN LATE-ONSET PARK;

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.