Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PINK1 (Q9BXM7) - Overview - Molecular Target Synopsis

Protein


PINK1, Serine/threonine-protein kinase PINK1, mitochondrial
Enzyme Classification 2.7.11.1
UniProt Q9BXM7

Also Known as PINK1_HUMAN, PINK1

Protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins. Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy) by mediating activation and translocation of PRKN (PubMed:14607334, PubMed:15087508, PubMed:19229105, PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:23620051, PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:24896179, PubMed:25527291). Targets PRKN to dysfunctional depolarized mitochondria through the phosphorylation of MFN2 (PubMed:23620051). Activates PRKN in 2 steps: (1) by mediating phosphorylation at 'Ser-65' of PRKN and (2) mediating phosphorylation of ubiquitin, converting PRKN to its fully-active form (PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25527291). Required for ubiquinone reduction by mitochondrial complex I by mediating phosphorylation of complex I subunit NDUFA10. Interacts with PRKN. Interacts with FBXO7. Forms a complex with PRKN and PARK7 (PubMed:19229105).

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
581ENSG00000158828ENST00000321556ENSP00000364204Q9BXM7-1
274Q9BXM7-2

Sub-cellular localization


UniProt: PINK1 is active in the following subcellular-locations: cytoplasm, cytosol, mitochondrion inner membrane, mitochondrion outer membrane.
GO terms: PINK1 is active in the following subcellular-locations: astrocyte projection, axon, cell body, chromatin, cytoplasm, cytoskeleton, cytosol, growth cone, integral component of mitochondrial outer membrane, Lewy body, membrane, mitochondrial inner membrane, mitochondrial intermembrane space, mitochondrial outer membrane, mitochondrion, nucleus, perinuclear region of cytoplasm.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PINK1 has gain in 2 cell-lines, loss in 0 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SN12C, SK_OV_3, PC_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Hs 746T, SCC-9, M059J

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: BJ, HeLa-S3, IMR-90

(see details)

RNA Interference


PINK1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SUM44, MDAMB453. (see details)

3D Structures


At greater than 35% identity similarity to PINK1 there are:
3 structures (8 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis