park (parkin, Q7KTX7, FBgn0041100) - manual literature synthesis

No deep-research provider was available for this review. This summary was written by the
reviewer from cached publications in publications/ and the UniProt record
(park-uniprot.txt). Every claim carries its provenance.

Identity and domain architecture

• Drosophila melanogaster parkin, 482 aa, the single fly ortholog of human PRKN. UniProt
  places it in the RBR family, parkin subfamily: "Belongs to the RBR family. Parkin
  subfamily." [file:genes/DROME/park/park-uniprot.txt]
• Domains: N-terminal ubiquitin-like (Ubl, 30-99), RING0, RING1, IBR and RING2 (Rcat)
  zinc-binding domains; InterPro IPR003977 Parkin, IPR031127 E3_UB_ligase_RBR.
• Catalytic cysteine: Cys449 of the fly protein (Cys431 in human) on RING2 PMID:23770917.

Enzymatic activity

• RBR E3 ligase, E2-dependent: PMID:17456438; E2 binding is via RING1 PMID:17456438.
• Autoubiquitination PMID:17456438; autoubiquitination occurs only in cis PMID:23770917.
• Activation by PINK1: phosphorylation of Ser94 in the Ubl PMID:24901221; phospho-Ser94 is required
  for activation but not for translocation in the fly eye PMID:27906179.
  An earlier paper reported a linker-region phosphorylation promoting translocation
  PMID:18957282.

Substrates (fly proteins, or fly orthologs assayed)

• Marf (mitofusin): PMID:20194754; co-IP PMID:20194754;
  PMID:24898855.
• Porin/VDAC: mono- and polyubiquitination PMID:32047033.
• Paris: PMID:32138754.
• Koi (LINC complex, in vitro): PMID:29689197.
• Septins peanut and Septin1: PMID:17456438.

Localization

• Cytosolic at rest, recruited to mitochondria upon depolarization in a PINK1-dependent manner
  PMID:20194754;
  PMID:24901221;
  PMID:27906179.
• Recruitment is transient and to the cytosolic face of the outer membrane; no ER or Golgi
  localization has been reported for the fly protein in the cached literature.

Processes

• Mitophagy: PMID:20194754; in vivo turnover PMID:23509287; developmental clearance of mitochondria in the
  intestine PMID:37633267;
  heart PMID:24192653.
• Mitochondrial dynamics: loss raises Marf and elongates mitochondria PMID:20194754; genetic interactions suggest the pathway promotes fission and/or
  inhibits fusion, but parkin is not part of the fission machinery PMID:18799731.
• Mutant phenotypes (downstream of mitochondrial dysfunction): muscle degeneration, male
  sterility PMID:12642658; spermatid mitochondrial derivative defects PMID:17123504;
  DA neuron degeneration PMID:15911761; JNK hyperactivation PMID:16002472; female sterility
  PMID:20869429; oxidative stress/metal sensitivity [PMID:20483372; PMID:21383066]; ATP
  synthase defects rescued by GstO1 PMID:22219196;
  circadian and memory phenotypes PMID:28435104.