ATP5PO (OSCP) review notes

UniProtKB:P48047 · HGNC:850 · gene ATP5PO (syn. ATP5O, ATPO) · 213 aa precursor
(transit peptide 1-23; mature chain 24-213). Family: ATPase delta chain family.

Function (verified biology)

ATP5PO encodes the oligomycin sensitivity conferral protein (OSCP), the subunit at
the top of the peripheral (stator) stalk of the mitochondrial F1Fo ATP synthase
(Complex V). It caps the F1 catalytic head and, together with the b/F6/d subunits, forms
the stationary peripheral stalk that holds the F1 alpha3beta3 catalytic hexamer static
against the rotating central stalk — essential for coupling proton flux through Fo to ATP
synthesis in F1. It is a structural (non-catalytic) subunit; it confers oligomycin
sensitivity on the complex.

• UniProt FUNCTION [P48047]: "Subunit OSCP, of the mitochondrial membrane ATP synthase
  complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence
  of a proton gradient across the membrane... Part of the complex F(0) domain and the
  peripheric stalk, which acts as a stator to hold the catalytic alpha(3)beta(3) subcomplex
  and subunit a/ATP6 static relative to the rotary elements."
• UniProt SUBUNIT: peripheral stalk = subunits F6, b, d, and OSCP. PMID:37244256
• Cryo-EM structure of the human ATP synthase resolves OSCP (chain O, residues 24-213):
  PMID:37244256

Key experimental anchors

• PMID:12110673 (IDA): human F1Fo ATP synthase immunocaptured from heart/fibroblasts;
  OSCP identified as a bona fide subunit; complex V displayed oligomycin-sensitive ATP
  hydrolysis. Supports part_of ATP synthase complex + contributes_to rotational MF.
• PMID:15850986 (IMP / IDA): OSCP is the binding target of the F1Fo-ATPase inhibitor
  Bz-423; RNAi knockdown of OSCP changes cellular sensitivity, functionally implicating
  OSCP in ATP synthase activity → supports involved_in proton motive force-driven mito ATP
  synthesis (GO:0042776) and mitochondrion localization.
• PMID:7490082 (cloning, NAS): "This ATP5O subunit is a key structural component of the
  stalk of the mitochondrial respiratory chain F1F0-ATP synthase." Supports the structural
  role and part_of complex.
• PMID:30266287 (IPI with PPID/Cyclophilin D, Q08752): OSCP interacts with Cyclophilin
  D and with amyloid-beta; CypD/OSCP is functionally linked to the permeability transition
  pore and F1Fo ATP synthase dysfunction in AD. This is the one functionally-informative
  interaction among the IPI set.
• PMID:34954817 (not cached): biallelic ATP5PO variants → Mitochondrial complex V
  deficiency, nuclear type 7 (MC5DN7); confirms essential role in complex V. Recorded from
  the UniProt DISEASE line.

Localization

• Mitochondrial inner membrane (GO:0005743) — anatomical location of the complex; supported
  by Reactome TAS, ComplexPortal NAS (PMID:26297831), and UniProt SubCell.
• Mitochondrion (GO:0005739) — multiple IDA/HDA/IBA.
• Plasma membrane (PMID:17851741, IDA) and cell surface (Ensembl IEA): "ecto-ATP synthase"
  — a minor, non-core surface pool reported on HepG2 hepatocytes; keep as non-core.
• Nucleus (GO:0005634, HDA PMID:21630459): sperm-nucleus proteomics; contaminant / non-core.

Annotation decisions summary

• Core: structural molecule activity (GO:0005198, authored MF); part_of proton-transporting
  ATP synthase complex (GO:0045259); involved_in proton motive force-driven mitochondrial
  ATP synthesis (GO:0042776); located_in mitochondrial inner membrane (GO:0005743).
• contributes_to GO:0046933 (rotational ATP synthase MF): ACCEPT — correct "contributes_to"
  usage for a non-catalytic subunit of the catalytic complex.
• enables GO:0046933 (InterPro IEA): MODIFY → the enables/contributes_to distinction
  matters; OSCP does not itself enable the rotary catalytic MF. Downgrade to structural role.
• GO:0016887 ATP hydrolysis activity (contributes_to, Ensembl IEA): MARK_AS_OVER_ANNOTATED —
  in vivo OSCP/complex only synthesizes; hydrolysis is an artificial in-vitro reverse activity.
• estradiol binding (GO:1903924), cellular response to cAMP (GO:0071320), cellular response to cytokine stimulus (GO:0071345): Ensembl orthology-transferred from rat; not
  core OSCP functions → MARK_AS_OVER_ANNOTATED.
• Bare protein binding IPIs (GO:0005515): MARK_AS_OVER_ANNOTATED per policy (uninformative),
  not REMOVE.
• nucleus, cell surface, plasma membrane: KEEP_AS_NON_CORE (minor/contaminant pools).