PIGBOS1 (A0A0B4J2F0) review notes

2026-09-30 session (claude-code)

54-aa microprotein encoded by a smORF in exon 2 of a transcript on the opposite strand of PIGB
(chr15). UniProt: single TM helix (aa 5-25), N-terminus (1-4) in IMS, C-terminus (26-54)
cytoplasmic; region 30-36 required for CLCC1 binding. Pfam PF23670 / InterPro IPR057394
(PIGBOS1 family); PAN-GO has 0 IBA annotations. No paralogs.
PMID:31653868
Translation shown by a tryptic peptide and antibodies:
PMID:31653868
NB: the Chu et al. paper is Nat Commun 2019 (PMID:31653868), not Cell Chem Biol as in the task brief.
PMID verified by E-utilities and cached full text (PMC6814811).

MOM by fractionation, IF colocalization with Tom20, proteinase K protection assay, split-GFP:
PMID:31653868
Signal-anchor topology:
PMID:31653868
MitoCoP high-confidence mitochondrial proteome (HTP) includes PIGBOS1:
PMID:34800366
ER-mitochondria contacts: PIGBOS-CLCC1 split-GFP signal peaks between the ER and MOM markers, but PIGBOS
is not a tether (no ERMICC change in KO; overexpression does not remodel contacts).
PMID:31653868
GOA gives CLCC1 (Q96S66) GO:0044233 (MAM contact site, IDA, PMID:31653868) but gives PIGBOS only MOM.
Comparator check: MOM-side contact-site proteins RMDN3/PTPIP51 (Q96TC7), MFN2 (O95140) and VAPA
(Q9P0L0) carry no direct GO:0044233 annotation in QuickGO. So I do NOT propose GO:0044233 as NEW;
the curator's choice (CLCC1 = MAM fraction; PIGBOS = MOM) is consistent with the data.

IP-MS + SAINT/CRAPome, APEX proximity labelling, reciprocal co-IP, split-GFP, flow cytometry.
Region 30-36 critical:
PMID:31653868
Interaction not regulated by ER stress (IP and split-GFP after TM/TG).
CLCC1 has GO:0005254 chloride channel activity (IDA PMID:37142673, plus IBA) in GOA, so it qualifies
as a transmembrane transporter; GO:0044325 transmembrane transporter binding is the informative
replacement for the bare protein binding row.
Homo-oligomerization (human-human and human-rat co-IP); TMDOCK predicts TM homodimer. Not proposed
as an MF term (binding term of little value).

Loss (siRNA KD, CRISPR KO) -> heightened XBP1 splicing, ATF6 reporter, all UPR target genes;
rescue by siRNA-resistant PIGBOS; overexpression dampens UPR. Directional in both senses, so the
annotation can be sharpened to negative regulation (GO:1900102).
PMID:31653868
PMID:31653868
Requires CLCC1 binding: C-terminal truncation and 30-32 AAA mutant fail to rescue:
PMID:31653868
Specific to ER UPR (no effect on mitoUPR with CDDO); increased ER-stress apoptosis (caspase-3,
PARP cleavage) in KD/KO cells, but staurosporine-induced death unchanged. The apoptosis effect is
treated as a downstream consequence of heightened UPR; no NEW apoptosis term proposed.

Aditya & Bera 2026 (PMID:42351194, single lab, HEK293T): PIGBOS promotes IP3R-mediated ER Ca2+
release, ER-to-mitochondria Ca2+ transfer and SOCE, all dependent on CLCC1-binding C-terminus;
loss impairs respiration and ATP.
PMID:42351194
Mechanism is explicitly unresolved (direct vs via intermediaries), and much is expression-level
change of Ca2+ machinery. Not proposed as NEW; raised as a suggested question.
MitoCoP q-AP-MS (PMID:34800366): FLAG-PIGBOS1 copurified HIGD2A and complex III/IV subunits,
PMID:34800366
Hard to reconcile with a MOM signal-anchor protein whose IMS-facing part is only ~4 residues;
could reflect digitonin-solubilized overexpressed protein. Not used for annotation.

41465308 (review on microproteins), 41277184 (oocyte aging omics), 40287452 (horse astaxanthin),
31858090 (AD hypothesis), 29100423 (lncRNA biomarker melanoma) - incidental mentions; not used.

protein binding IPI (CLCC1) -> MODIFY to GO:0044325 transmembrane transporter binding
mitochondrion HTP -> ACCEPT (less specific than MOM)
MOM IDA -> ACCEPT (core)
MOM IEA -> ACCEPT
regulation of ER UPR IMP -> MODIFY to GO:1900102 negative regulation of ER UPR
No NEW terms.