Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9BXM7: Variant p.Gln126Pro

Serine/threonine-protein kinase PINK1, mitochondrial
Gene: PINK1
Feedback?
Variant information Variant position: help 126 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Glutamine (Q) to Proline (P) at position 126 (Q126P, p.Gln126Pro). 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: help Change from medium size and polar (Q) to medium size and hydrophobic (P) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In PARK6; strongly reduces interaction with PRKN; under depolarizing conditions, it fails to support PINK1-TOM-TIM23 complex assembly and mitophagy activation; loss of autophosphorylation on S-228 and kinase activation; no effect on interaction with TIMM23. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 126 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 581 The length of the canonical sequence.
Location on the sequence: help LGLGLIEEKQAESRRAVSAC Q EIQAIFTQKSKPGPDPLDTR 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         LGLGLI-EEKQAESRRAVSACQEIQAIFTQ-----KSKPGPDPLDTR

Mouse                         LGLGLI-EEKQAEGRRAASACQEIQAIFTQ-----KTKRVS

Rat                           LGLGLI-EEKQAESRRAASACQEIQAIFTQ-----KNKQVS

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

Drosophila                    SGSGVLSKEDELEG-----VCWEIREAASRLQNAWNHDEIS
Sequence annotation in neighborhood: help 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 78 – 581 Serine/threonine-protein kinase PINK1, mitochondrial
Topological domain 111 – 581 Cytoplasmic
Alternative sequence 1 – 307 Missing. In isoform 2.
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
The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations.
Geisler S.; Holmstrom K.M.; Treis A.; Skujat D.; Weber S.S.; Fiesel F.C.; Kahle P.J.; Springer W.;
Autophagy 6:871-878(2010)
Cited for: FUNCTION IN MITOCHONDRIAL AUTOPHAGY; SUBCELLULAR LOCATION; INTERACTION WITH PRKN; CHARACTERIZATION OF VARIANTS PARK6 PRO-126; ASP-309 AND PRO-347; 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; Mechanism of human PINK1 activation at the TOM complex in a reconstituted system.
Raimi O.G.; Ojha H.; Ehses K.; Dederer V.; Lange S.M.; Rivera C.P.; Deegan T.D.; Chen Y.; Wightman M.; Toth R.; Labib K.P.M.; Mathea S.; Ranson N.; Fernandez-Busnadiego R.; Muqit M.M.K.;
Sci. Adv. 10:Eadn7191-Eadn7191(2024)
Cited for: INTERACTION WITH TOMM20; MUTAGENESIS OF LEU-532; LEU-539 AND LEU-540; CHARACTERIZATION OF VARIANTS PRO-126; LYS-240; ASP-309 AND GLN-534 INS; Clinical and molecular characterisation of a Parkinson family with a novel PINK1 mutation.
Prestel J.; Gempel K.; Hauser T.K.; Schweitzer K.; Prokisch H.; Ahting U.; Freudenstein D.; Bueltmann E.; Naegele T.; Berg D.; Klopstock T.; Gasser T.;
J. Neurol. 255:643-648(2008)
Cited for: VARIANT PARK6 PRO-126;
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.