PRKN notes

Deep research was not run: falcon times out in this environment and perplexity-lite is not installed. These notes are based on the 96 cached publications and the UniProt record.

Core biology

• A RING-type (RBR) E3 that binds UbcH7/UbcH8 PMID:10973942
• C431 is the catalytic cysteine and is needed for mitophagy PMID:23770887.
• Activated by PINK1 through phospho-Ser65 ubiquitin [PMID:24660806, PMID:24751536] and phosphorylation of Ser65 in its Ubl PMID:23754282.
• Recruited to depolarized mitochondria, where it drives mitophagy PMID:19029340
• Builds K6, K11 and K63 chains on mitochondria, which USP30 opposes PMID:25621951.
• Many non-mitochondrial substrates: Pael-R PMID:11439185, PARIS PMID:21376232, Fbw7beta PMID:23858059, RIPK3 PMID:31358971, NEMO via LUBAC PMID:23453807. These were kept as non-core.

Curation decisions

• Neuronal and synaptic IEA locations and neuroprotection processes were kept as non-core. Stress-response IEAs transferred from rodent studies were marked as over-annotated.
• Protein deubiquitination (Reactome TAS) was removed, because Parkin is a substrate of DUBs and does not carry out deubiquitination.
• The midnolin paper (PMID:24187134) reports only an overexpression effect on insulin secretion and glucokinase, so these annotations were marked as over-annotated.
• Host-mediated suppression of viral genome replication (PMID:25244949, abstract only) was left UNDECIDED. The abstract implies Parkin supports HCV propagation.
• All 77 protein binding rows were removed.