PPIB PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: P23284
- AIGR review status: COMPLETE
- Review batch: proteostasis-batch-2026-06-07b
- Batch change status: added
Source Files Checked
Deep Research Files
- No
*-deep-research*.md file found in this gene directory.
AIGR Review Snapshot
- Description: PPIB (peptidyl-prolyl cis-trans isomerase B; cyclophilin B / CypB; also called S-cyclophilin/SCYLP and rotamase B) is an endoplasmic reticulum-lumenal cyclophilin-type peptidyl-prolyl cis-trans isomerase (EC 5.2.1.8) that catalyzes the rate-limiting cis-trans isomerization of Xaa-Pro peptide bonds and thereby accelerates protein folding. It is retained in the ER lumen by a C-terminal retention motif and is a component of ER chaperone/foldase complexes, including the prolyl 3-hydroxylation complex with P3H1 (LEPRE1) and CRTAP that processes procollagen, and an ERp72(PDIA4)-cyclophilin B module that accelerates immunoglobulin folding. Loss-of-function mutations in PPIB cause autosomal-recessive osteogenesis imperfecta type IX, underscoring its role in collagen biogenesis and bone development. Beyond the ER, a secreted/cell-surface pool of cyclophilin B signals through the receptor CD147/EMMPRIN to promote leukocyte (neutrophil) chemotaxis, and the protein is exploited as a host factor by certain viruses (e.g. hepatitis C virus NS5B polymerase, measles virus). Its PPIase activity is inhibited by the immunosuppressant cyclosporin A.
- Existing/core annotation action counts: ACCEPT: 19; KEEP_AS_NON_CORE: 32; MARK_AS_OVER_ANNOTATED: 2
PN Consistency Summary
- Consistency: Fully consistent. Review, notes, and UniProt agree PPIB is a genuine ER-lumenal cyclophilin-type PPIase (EC 5.2.1.8, CsA-inhibited) and a component of the P3H1/CRTAP/PPIB collagen prolyl-3-hydroxylation complex; LoF causes osteogenesis imperfecta type IX. Both PN mappings align with the review's two core functions.
- PN story / NEW pressure: Two projections. (1) GO:0003755 (VERIFIED real) is already in GOA exact (IEA/IDA/ISS/NAS — confirmed in goa.tsv) and ACCEPTed as core — already captured, correct. (2) GO:0032964 collagen biosynthetic process (VERIFIED real via OLS) is NOT in PPIB GOA (confirmed: GOA has only collagen binding GO:0005518 and bone development GO:0060348) — a defensible NEW BP capturing PPIB's collagen-maturation role. Conclude: GO:0003755 already captured; GO:0032964 = ADD (defensible, real, novel-to-GOA).
- Evidence alignment: PN node carries no reference titles, but review evidence directly supports both stories: PMID:20676357 / PMID:2000394 (PPIase activity, VERIFIED), PMID:39245686 (P3H1/CRTAP/PPIB collagen complex) and PMID:20089953 (PPIB-null OI) for the collagen/bone biology. Note the nuanced NOT|protein folding and NOT|regulation of PTM (PMID:20089953: PPIB-null OI has normal collagen folding) — these qualify, but do not contradict, the broader collagen-biosynthesis role.
- Verdict: CONSISTENT — GO:0003755 already captured (correct); GO:0032964 is a sound NEW addition. Recommended edits: [YAML] consider adding GO:0032964 collagen biosynthetic process (involved_in) to PPIB existing/proposed terms, supported by PMID:39245686 + OI9 genetics, to align the review with the defensible PN projection.
Full Consistency Review
- UniProt: P23284 · batch: proteostasis-batch-2026-06-07b · review status: COMPLETE (exhaustive; ~55 annotations, notes present, no provider deep-research file)
- PN placement (2 rows):
ER proteostasis|Folding enzyme|Peptidyl-prolyl isomerases|Cyclophilin type and ER proteostasis|Maturation and folding of specific substrates|ER collagen processing and folding ; PN-node mapping: type+group (PPIases / Cyclophilin type)→GO:0003755 peptidyl-prolyl cis-trans isomerase activity (mapped/ok_for_propagation, already_in_goa_exact); collagen group→GO:0032964 collagen biosynthetic process (mapped/ok_for_propagation, new_to_goa); class/branch→no_mapping.
- Consistency: Fully consistent. Review, notes, and UniProt agree PPIB is a genuine ER-lumenal cyclophilin-type PPIase (EC 5.2.1.8, CsA-inhibited) and a component of the P3H1/CRTAP/PPIB collagen prolyl-3-hydroxylation complex; LoF causes osteogenesis imperfecta type IX. Both PN mappings align with the review's two core functions.
- PN story / NEW pressure: Two projections. (1) GO:0003755 (VERIFIED real) is already in GOA exact (IEA/IDA/ISS/NAS — confirmed in goa.tsv) and ACCEPTed as core — already captured, correct. (2) GO:0032964 collagen biosynthetic process (VERIFIED real via OLS) is NOT in PPIB GOA (confirmed: GOA has only collagen binding GO:0005518 and bone development GO:0060348) — a defensible NEW BP capturing PPIB's collagen-maturation role. Conclude: GO:0003755 already captured; GO:0032964 = ADD (defensible, real, novel-to-GOA).
- Mapping strategy: Mappings are appropriately scoped — narrow, member-supported MF/BP terms, not over-broad umbrellas (unlike the TOMM20/HSPA8/RAB7A rejections). GO:0032964 is well-matched to PPIB's documented collagen-processing function and bone-disease genetics. No mapping change needed.
- Evidence alignment: PN node carries no reference titles, but review evidence directly supports both stories: PMID:20676357 / PMID:2000394 (PPIase activity, VERIFIED), PMID:39245686 (P3H1/CRTAP/PPIB collagen complex) and PMID:20089953 (PPIB-null OI) for the collagen/bone biology. Note the nuanced NOT|protein folding and NOT|regulation of PTM (PMID:20089953: PPIB-null OI has normal collagen folding) — these qualify, but do not contradict, the broader collagen-biosynthesis role.
- Verdict: CONSISTENT — GO:0003755 already captured (correct); GO:0032964 is a sound NEW addition. Recommended edits: [YAML] consider adding GO:0032964 collagen biosynthetic process (involved_in) to PPIB existing/proposed terms, supported by PMID:39245686 + OI9 genetics, to align the review with the defensible PN projection.
PN Dossier Context
- review_batch: proteostasis-batch-2026-06-07b
- review_yaml: genes/human/PPIB/PPIB-ai-review.yaml
- PN workbook rows: 2
PN row 1: ER proteostasis | Folding enzyme | Peptidyl-prolyl isomerases | Cyclophilin type
- UniProt: P23284
- In branches: ER
- PN-node mapping records (path + ancestors):
- [type] ER proteostasis|Folding enzyme|Peptidyl-prolyl isomerases|Cyclophilin type
status=mapped scope=ok_for_propagation_to_go GO=[GO:0003755 peptidyl-prolyl cis-trans isomerase activity]
rationale: This PN type denotes ER cyclophilin-family PPIases. The matching GO molecular function is appropriate for propagation.
- [group] ER proteostasis|Folding enzyme|Peptidyl-prolyl isomerases
status=mapped scope=ok_for_propagation_to_go GO=[GO:0003755 peptidyl-prolyl cis-trans isomerase activity]
rationale: This PN group is the ER peptidyl-prolyl isomerase family. The GO PPIase activity term is the appropriate propagation target for this folding enzyme bucket.
- [class] ER proteostasis|Folding enzyme
status=no_mapping scope= GO=[]
rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
- [branch] ER proteostasis
status=no_mapping scope= GO=[]
rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.
PN row 2: ER proteostasis | Maturation and folding of specific substrates | ER collagen processing and folding
- UniProt: P23284
- In branches: ER
- PN-node mapping records (path + ancestors):
- [group] ER proteostasis|Maturation and folding of specific substrates|ER collagen processing and folding
status=mapped scope=ok_for_propagation_to_go GO=[GO:0032964 collagen biosynthetic process]
rationale: This PN group contains ER factors dedicated to collagen maturation, processing, and folding. Collagen biosynthetic process captures the shared substrate-specific pathway context.
- [class] ER proteostasis|Maturation and folding of specific substrates
status=no_mapping scope= GO=[]
rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
- [branch] ER proteostasis
status=no_mapping scope= GO=[]
rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.
Projected GO annotations (3)
- GO:0003755 peptidyl-prolyl cis-trans isomerase activity | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=ER proteostasis|Folding enzyme|Peptidyl-prolyl isomerases
- GO:0003755 peptidyl-prolyl cis-trans isomerase activity | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=ER proteostasis|Folding enzyme|Peptidyl-prolyl isomerases|Cyclophilin type
- GO:0032964 collagen biosynthetic process | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=ER proteostasis|Maturation and folding of specific substrates|ER collagen processing and folding
Note
This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.