PINK1 notes

Deep research was not run: falcon times out in this environment and perplexity-lite is not installed. These notes are based on the 59 cached publications and the UniProt record.

Core biology

• Phosphorylates ubiquitin at Ser65 [PMID:24751536 "Using mass spectrometry, we discovered that endogenous PINK1 phosphorylated ubiquitin at serine 65, homologous to the site phosphorylated by PINK1 in Parkin's ubiquitin-like domain."; PMID:24660806 "Remarkably, PINK1 directly phosphorylates Ser65 of ubiquitin in vitro."]
• Phosphorylates Ser65 in the Parkin Ubl domain PMID:24660806, and polyubiquitin chains PMID:25474007.
• Stabilized on the outer membrane of depolarized mitochondria, where it recruits Parkin PMID:22354088.
• The kinase domain faces the cytoplasm PMID:18687899. PARL cleaves PINK1 in healthy mitochondria PMID:21426348.
• Other substrates: Miro PMID:22078885, DRP1 S616 PMID:32484300, TRAP1 PMID:17579517.

Curation decisions

• Annotations from PMID:19279012 (PINK1 knockdown increases mitophagy and fragmentation via oxidative stress) were marked as over-annotated, as indirect effects that run opposite to the canonical pathway.
• Positive regulation of cytochrome c release (IMP, PMID:19880420) was changed (MODIFY) to the negative regulation term. The full text shows that PINK1 depletion enhanced cytochrome c release.
• Terms that GOA labels obsolete (GO:1903747/GO:1903749) were changed to GO:0070585 protein localization to mitochondrion (PINK1-dependent recruitment of Parkin).
• All 34 protein binding rows were removed.

2026-11-05 ORGANELLES ER batch 3 (endoplasmic reticulum rows)

Rows: GO:0005783 IDA (PMID:31536960) and GO:0005783 IEA (GO_REF:0000120; ARBA:ARBA00028672 plus mouse/rat orthologs). No ER sub-compartment rows.

Checks:
- PMID:31536960 (full text): endogenous PINK1 immunoprecipitated from marker-controlled ER, mitochondrial and MAM fractions, where it binds NENF PMID:31536960.
- Human UniProt no longer lists the ER (mitochondrial outer/inner membrane, cytosol only); mouse Q99MQ3 and rat B5DFG1 (UniProt REST, 2026-11-05) list no ER either. The IEA therefore rests on the ARBA rule, an unvetted prediction.
- PINK1 has a mitochondrial transit peptide (1-77) and no ER-targeting signal.

Outcome: both rows stay KEEP_AS_NON_CORE (reasons updated). The IEA would be MARK_AS_OVER_ANNOTATED on its own source, but it makes the same claim as the IDA row and the two take the same action. Stays at the root; a MAM pool during mitophagy is reported in the literature but was not checked here (no cached source).