UniProtKB/Swiss-Prot Q9BXM7: Variant p.Gln115Leu

Serine/threonine-protein kinase PINK1, mitochondrial
Gene: PINK1
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Variant information Variant position:

115 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 Glutamine (Q) to Leucine (L) at position 115 (Q115L, p.Gln115Leu). 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 (Q) to medium size and hydrophobic (L) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 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:

Under depolarizing conditions, does not affect PINK1-TOM-TIM23 complex assembly and mitophagy activation; no effect on interaction with TIMM23. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs148871409 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

PCGRAVFLAFGLGLGLIEEK Q AESRRAVSACQEIQAIFTQK 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                         PCGRAVFLAFGLGLGLI-EEKQAESRRAVSACQEIQAIFTQ-----K

Mouse                         PCGRAVFLAFGLGLGLI-EEKQAEGRRAASACQEIQAIFTQ

Rat                           PCGRAVFLAFGLGLGLI-EEKQAESRRAASACQEIQAIFTQ

Caenorhabditis elegans        ------------------QPIRKELPRNVDLVERIRQIFG-

Drosophila                    PFFALIGVSLASGSGVLSKEDELEG-----VCWEIREAASR

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	78 – 581	Serine/threonine-protein kinase PINK1, mitochondrial
Topological domain	111 – 581	Cytoplasmic
Region	111 – 117	Required for outer membrane localization
Alternative sequence	1 – 307	Missing. In isoform 2.
Mutagenesis	112 – 117	EEKQAE -> AAKQAA. In 3EA; impaired ability to localize to the outer mitochondrial membrane.
Mutagenesis	131 – 131	I -> E. Under depolarizing conditions, it results in loss of interaction with TOMM20 and fails to support PINK1-TOM-TIM23 complex assembly and mitophagy activation.

Literature citations
TIM23 facilitates PINK1 activation by safeguarding against OMA1-mediated degradation in damaged mitochondria.
Akabane S.; Watanabe K.; Kosako H.; Yamashita S.I.; Nishino K.; Kato M.; Sekine S.; Kanki T.; Matsuda N.; Endo T.; Oka T.;
Cell Rep. 42:112454-112454(2023)
Cited for: INTERACTION WITH TIMM23; CHARACTERIZATION OF VARIANTS LEU-52; PHE-67; PRO-68; VAL-78; PHE-92; TRP-98; SER-111; LEU-115; VAL-124; GLY-125; PRO-126; MET-145; HIS-147; TRP-148; PRO-168; LYS-240; GLN-271; ASP-309; PRO-347; ALA-386; VAL-409; GLY-417 AND GLN-534 INS; Tom20 gates PINK1 activity and mediates its tethering of the TOM and TIM23 translocases upon mitochondrial stress.
Eldeeb M.A.; Bayne A.N.; Fallahi A.; Goiran T.; MacDougall E.J.; Soumbasis A.; Zorca C.E.; Tabah J.J.; Thomas R.A.; Karpilovsky N.; Mathur M.; Durcan T.M.; Trempe J.F.; Fon E.A.;
Proc. Natl. Acad. Sci. U.S.A. 121:e2313540121-e2313540121(2024)
Cited for: INTERACTION WITH TOM AND TIM23 COMPLEXES; INTERACTION WITH TOMM20; MUTAGENESIS OF ILE-131; ALA-536; LEU-540 AND ARG-543; CHARACTERIZATION OF VARIANTS SER-111; LEU-115; GLY-125 AND PRO-126; PINK1, Parkin, and DJ-1 mutations in Italian patients with early-onset parkinsonism.
Klein C.; Djarmati A.; Hedrich K.; Schaefer N.; Scaglione C.; Marchese R.; Kock N.; Schuele B.; Hiller A.; Lohnau T.; Winkler S.; Wiegers K.; Hering R.; Bauer P.; Riess O.; Abbruzzese G.; Martinelli P.; Pramstaller P.P.;
Eur. J. Hum. Genet. 13:1086-1093(2005)
Cited for: VARIANTS PARK6 HIS-279 AND GLN-534 INS; VARIANT LEU-115; Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes.
Bonifati V.; Rohe C.F.; Breedveld G.J.; Fabrizio E.; De Mari M.; Tassorelli C.; Tavella A.; Marconi R.; Nicholl D.J.; Chien H.F.; Fincati E.; Abbruzzese G.; Marini P.; De Gaetano A.; Horstink M.W.; Maat-Kievit J.A.; Sampaio C.; Antonini A.; Stocchi F.; Montagna P.; Toni V.; Guidi M.; Dalla Libera A.; Tinazzi M.; De Pandis F.; Fabbrini G.; Goldwurm S.; de Klein A.; Barbosa E.; Lopiano L.; Martignoni E.; Lamberti P.; Vanacore N.; Meco G.; Oostra B.A.;
Neurology 65:87-95(2005)
Cited for: VARIANTS PARK6 PRO-168 AND LEU-196; VARIANTS LEU-115; THR-340; LYS-476 AND THR-521;

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.