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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006457 protein folding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: As a PPIase, PPIB accelerates proline-limited steps of protein folding; protein folding is a valid downstream process of its isomerase activity. Reason: Protein folding is the biological-process consequence of PPIB's peptidyl-prolyl isomerase molecular function rather than the function itself; appropriate as non-core. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt may therefore assist protein folding |
| GO:0016018 cyclosporin A binding | IBA GO_REF:0000033 | ACCEPT | Summary: PPIB is a cyclophilin whose PPIase activity is inhibited by cyclosporin A; CsA binding is a defining property of the cyclophilin family and is structurally documented. Reason: Cyclosporin A binding is a genuine, structurally documented property of cyclophilin B (crystal structure with CsA) and the basis for inhibition of its PPIase activity. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt Inhibited by cyclosporin A (CsA). |
| GO:0003755 peptidyl-prolyl cis-trans isomerase activity | IEA GO_REF:0000120 | ACCEPT | Summary: This is the core molecular function of PPIB - catalysis of peptidyl-proline cis-trans isomerization (EC 5.2.1.8, RHEA:16237). Reason: Matches PPIB's documented catalytic activity and is the central, experimentally validated function of cyclophilin B. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt EC=5.2.1.8 |
| GO:0005788 endoplasmic reticulum lumen | IEA GO_REF:0000044 | ACCEPT | Summary: PPIB is a soluble ER-lumenal protein with a C-terminal ER-retention motif; the precise core compartment. Reason: ER lumen is the documented localization, consistent with the retention motif and direct evidence. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0042470 melanosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: PPIB identified by mass spectrometry in melanosome fractions; a secondary localization. Reason: A proteomics-detected secondary localization, peripheral to the core ER-lumenal function. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt Identified by mass spectrometry in melanosome fractions |
| GO:0005515 protein binding | IPI PMID:15989969 Cyclophilin B is a functional regulator of hepatitis C virus... | KEEP AS NON CORE | Summary: Interaction with hepatitis C virus NS5B RNA polymerase (host-factor context). Bare protein binding is uninformative. Reason: A virus host-factor interaction; the generic protein binding term is uninformative and not part of PPIB's core PPIase function. Supporting Evidence: file:human/PPIB/PPIB-goa.tsv UniProtKB:Q9WMX2-PRO_0000037552 |
| GO:0005515 protein binding | IPI PMID:21280149 Dymeclin, the gene underlying Dyggve-Melchior-Clausen syndro... | KEEP AS NON CORE | Summary: Interaction with DYM (dymeclin), relevant to bone/secretory-pathway biology. Bare protein binding is uninformative. Reason: A documented interaction (DYM), but the generic protein binding term is uninformative and not the core function. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt P23284; Q7RTS9: DYM; NbExp=4; IntAct=EBI-359252, EBI-2871106; |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | KEEP AS NON CORE | Summary: Next-generation interactome dataset capturing a PPIB-SGTB (Q96EQ0) interaction. Bare protein binding is uninformative. Reason: High-throughput interaction; uninformative generic term, not part of the core function. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt P23284; Q96EQ0: SGTB; NbExp=4; IntAct=EBI-359252, EBI-744081; |
| GO:0005515 protein binding | IPI PMID:22665516 An interaction map of endoplasmic reticulum chaperones and f... | KEEP AS NON CORE | Summary: Interaction with ERp72/PDIA4 (P13667); PPIB and ERp72 form a functional module that accelerates IgG folding. The bare protein binding term is uninformative but the interaction is biologically meaningful. Reason: A functionally meaningful ER foldase-complex interaction (ERp72/PDIA4), but the generic protein binding term is uninformative; the informative role is captured as PPIase and ER chaperone-complex membership. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt P23284; P13667: PDIA4; NbExp=2; IntAct=EBI-359252, EBI-1054653; |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Proteome-scale interactome capturing PPIB binary interactions (e.g. SGTA, PEX19, BANP, UBQLN1). Bare protein binding is uninformative. Reason: High-throughput binary interactions; uninformative generic term, not core. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt P23284; O43765: SGTA; NbExp=6; IntAct=EBI-359252, EBI-347996; |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | KEEP AS NON CORE | Summary: Crosslinking mass-spectrometry study capturing a PPIB-PDIA4 interaction. Bare protein binding is uninformative. Reason: Records the PDIA4 interaction again; generic term, not core. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt P23284; P13667: PDIA4; NbExp=2; IntAct=EBI-359252, EBI-1054653; |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Reference binary interactome capturing PPIB interactions (e.g. HSPA6/P17066, SGTA, PEX19). Bare protein binding is uninformative. Reason: High-throughput binary interactions; uninformative generic term, not core. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt P23284; P17066: HSPA6; NbExp=3; IntAct=EBI-359252, EBI-355106; |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Neurodegeneration interactome capturing PPIB binary interactions (e.g. HOXC4, ID2, STIM1). Bare protein binding is uninformative. Reason: High-throughput binary interactions with mostly unrelated partners; uninformative generic term, not core. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt P23284; P09017: HOXC4; NbExp=3; IntAct=EBI-359252, EBI-3923226; |
| GO:0005790 smooth endoplasmic reticulum | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Smooth-ER localization inferred from the rat ortholog; a sub-compartment refinement of the ER localization. Reason: A plausible ER sub-compartment annotation transferred by similarity; subsumed by the core ER/ER-lumen localization. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0034663 endoplasmic reticulum chaperone complex | IEA GO_REF:0000107 | ACCEPT | Summary: PPIB is a component of a large ER chaperone/foldase multiprotein complex (with BiP, GRP94, PDIs, etc.); this localization/complex annotation is well supported. Reason: PPIB's membership in the ER chaperone complex is experimentally documented; the complex is the functional context for its foldase activity. Supporting Evidence: PMID:12475965 We demonstrate the existence of a large endoplasmic reticulum (ER)-localized multiprotein complex that is comprised of the molecular chaperones BiP; GRP94; CaBP1; protein disulfide isomerase (PDI); ERdj3, a recently identified ER Hsp40 cochaperone; cyclophilin B; ERp72; GRP170; UDP-glucosyltransferase; and SDF2-L1. |
| GO:0005515 protein binding | IPI PMID:39245686 The structural basis for the collagen processing by human P3... | KEEP AS NON CORE | Summary: Structural study of the P3H1/CRTAP/PPIB ternary complex (partner CRTAP/Q32P28) that processes collagen; the interaction is biologically central but the bare protein binding term is uninformative. Reason: A functionally important interaction (the collagen prolyl 3-hydroxylation complex), but the generic protein binding term is uninformative; the informative role is captured by the PPIase MF and collagen/bone process annotations. Supporting Evidence: file:human/PPIB/PPIB-goa.tsv UniProtKB:Q32P28 |
| GO:0005783 endoplasmic reticulum | IDA GO_REF:0000052 | ACCEPT | Summary: Direct (immunofluorescence) evidence for ER localization. Reason: IDA-supported ER localization, consistent with the core ER-lumenal compartment. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0042470 melanosome | EXP PMID:17081065 Proteomic and bioinformatic characterization of the biogenes... | KEEP AS NON CORE | Summary: Mass-spectrometry detection of PPIB in melanosome fractions (stages I-IV). Reason: A genuine but secondary proteomics localization, peripheral to the core ER-lumenal function. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt Identified by mass spectrometry in melanosome fractions |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9728804 | KEEP AS NON CORE | Summary: Reactome cytosol localization (likely a pathway/context assignment); not the principal compartment for this ER-lumenal protein. Reason: A curated localization for a specific pathway context; secondary to the core ER-lumen localization. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:20147391 CD147/EMMPRIN acts as a functional entry receptor for measle... | KEEP AS NON CORE | Summary: Interaction with measles virus nucleoprotein (microbial-infection context; partner Q9WMB5). Bare protein binding is uninformative. Reason: A virus host-factor interaction; the generic protein binding term is uninformative and not part of the core function. Supporting Evidence: file:human/PPIB/PPIB-goa.tsv UniProtKB:Q9WMB5 |
| GO:0030593 neutrophil chemotaxis | IDA PMID:11688976 CD147 is a signaling receptor for cyclophilin B. | KEEP AS NON CORE | Summary: Secreted/extracellular cyclophilin B signals through CD147/EMMPRIN to promote neutrophil chemotaxis; a genuine but specialized extracellular role distinct from the ER foldase function. Reason: A documented extracellular signaling function of the secreted pool (via CD147), but distinct from and non-core relative to PPIB's ER PPIase activity. Supporting Evidence: PMID:11688976 CD147 is a signaling receptor for cyclophilin B. |
| GO:0005518 collagen binding | ISS GO_REF:0000024 | ACCEPT | Summary: PPIB contributes to collagen binding within the prolyl 3-hydroxylation complex; collagen is a key substrate for its proline isomerization in collagen biogenesis. Reason: Collagen binding (contributes_to) is consistent with PPIB's role in the P3H1/CRTAP/PPIB complex acting on procollagen; supports its collagen-processing function. Supporting Evidence: PMID:39245686 collagen processing by human P3H1/CRTAP/PPIB ternary |
| GO:0003755 peptidyl-prolyl cis-trans isomerase activity | IDA PMID:20676357 Structural and biochemical characterization of the human cyc... | ACCEPT | Summary: Direct biochemical demonstration of PPIase activity for human cyclophilin B - the core molecular function. Reason: IDA-supported PPIase activity from biochemical characterization of the human cyclophilin family; the central function of PPIB. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds |
| GO:0044794 host-mediated activation of viral process | IMP PMID:15989969 Cyclophilin B is a functional regulator of hepatitis C virus... | KEEP AS NON CORE | Summary: Cyclophilin B acts as a host factor regulating HCV RNA polymerase; a specialized virus-host process. Reason: A genuine but specialized host-factor role in viral replication; non-core relative to PPIB's ER PPIase function. Supporting Evidence: PMID:15989969 Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase. |
| GO:0044829 host-mediated activation of viral genome replication | IMP PMID:15989969 Cyclophilin B is a functional regulator of hepatitis C virus... | KEEP AS NON CORE | Summary: Cyclophilin B promotes HCV genome replication via NS5B; a specialized virus-host role. Reason: A documented but specialized host-factor function in viral genome replication; non-core relative to the ER PPIase function. Supporting Evidence: PMID:15989969 Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:15989969 Cyclophilin B is a functional regulator of hepatitis C virus... | KEEP AS NON CORE | Summary: Perinuclear localization observed in the HCV-host-factor study; a context-specific localization. Reason: A context-specific (viral replication) localization; secondary to the core ER-lumen localization. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0070063 RNA polymerase binding | IPI PMID:15989969 Cyclophilin B is a functional regulator of hepatitis C virus... | KEEP AS NON CORE | Summary: Binding to HCV NS5B RNA-dependent RNA polymerase (a viral, not host, polymerase); a host-factor interaction rather than a general RNA polymerase binding function. Reason: The 'RNA polymerase binding' here reflects a specific interaction with the viral NS5B polymerase in a host-factor context, not a core cellular function of PPIB. Supporting Evidence: file:human/PPIB/PPIB-goa.tsv UniProtKB:Q9WMX2-PRO_0000037552 |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | KEEP AS NON CORE | Summary: High-throughput proteomics detection at focal adhesions; uninformative for this ER-lumenal protein. Reason: A proteomic-survey localization; secondary/peripheral to the core ER-lumen localization. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: Exosome proteomics detection; consistent with a secreted pool but a high-throughput localization. Reason: PPIB has a secreted pool, so exosome detection is plausible, but it is secondary to the core ER-lumen localization. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: Generic high-throughput membrane-proteome detection; uninformative for this soluble ER-lumenal protein. Reason: A generic proteomic localization; uninformative relative to the precise ER-lumen localization. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | KEEP AS NON CORE | Summary: Sperm-nucleus proteomics detection; a high-throughput localization not reflecting PPIB's principal compartment. Reason: A proteomic-survey localization (sperm nucleus); secondary/uninformative relative to the core ER-lumen localization. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | MARK AS OVER ANNOTATED | Summary: High-throughput mRNA-interactome capture identified PPIB; likely a non-specific RNA-binding signal for this PPIase. Reason: Detection in mRNA-interactome capture does not establish a specific, functional RNA-binding role for cyclophilin B; over-annotation for an ER foldase. Supporting Evidence: file:human/PPIB/PPIB-goa.tsv GO:0003723 |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | MARK AS OVER ANNOTATED | Summary: A second high-throughput mRNA-interactome capture identified PPIB; same caveat as above. Reason: A non-specific RNA-binding signal from proteome-wide RNA-interactome capture; not an established functional activity of PPIB. Supporting Evidence: file:human/PPIB/PPIB-goa.tsv GO:0003723 |
| GO:0003755 peptidyl-prolyl cis-trans isomerase activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS-transferred PPIase activity, consistent with the experimentally validated core function. Reason: Corroborates the IDA-supported core PPIase molecular function. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt EC=5.2.1.8 |
| GO:0032991 protein-containing complex | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Generic 'protein-containing complex' membership; correct but uninformative relative to the specific ER chaperone complex annotation. Reason: PPIB is part of defined complexes, but this generic term is uninformative; the specific ER chaperone complex term is preferred. Supporting Evidence: PMID:12475965 We demonstrate the existence of a large endoplasmic reticulum (ER)-localized multiprotein complex that is comprised of the molecular chaperones BiP; GRP94; CaBP1; protein disulfide isomerase (PDI); ERdj3, a recently identified ER Hsp40 cochaperone; cyclophilin B; ERp72; GRP170; UDP-glucosyltransferase; and SDF2-L1. |
| GO:0005783 endoplasmic reticulum | IDA PMID:20089953 Lack of cyclophilin B in osteogenesis imperfecta with normal... | ACCEPT | Summary: Direct evidence for ER localization in the osteogenesis imperfecta study. Reason: IDA-supported ER localization, consistent with the core ER compartment. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0006457 protein folding | IMP NOT PMID:20089953 Lack of cyclophilin B in osteogenesis imperfecta with normal... | ACCEPT | Summary: This is a NOT (negated) annotation - in PPIB-null osteogenesis imperfecta, collagen folding is NORMAL, unlike P3H1/CRTAP deficiency which delays collagen folding. Thus PPIB is not required for the overall rate of collagen folding in this assay. Reason: Supported by the finding that PPIB-deficient OI has normal collagen folding (no folding delay), distinguishing it from P3H1/CRTAP loss; the NOT annotation appropriately records that PPIB is not required for that folding step. Supporting Evidence: PMID:20089953 Lack of cyclophilin B in osteogenesis imperfecta with normal collagen folding. |
| GO:0040018 positive regulation of multicellular organism growth | IMP PMID:20089953 Lack of cyclophilin B in osteogenesis imperfecta with normal... | KEEP AS NON CORE | Summary: PPIB deficiency affects growth (osteogenesis imperfecta phenotype); a downstream organismal phenotype. Reason: An organism-level growth phenotype consequent to PPIB loss in bone; non-core relative to the PPIase molecular function. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt Osteogenesis imperfecta 9 (OI9) |
| GO:0050821 protein stabilization | IMP PMID:20089953 Lack of cyclophilin B in osteogenesis imperfecta with normal... | KEEP AS NON CORE | Summary: PPIB contributes to stabilization/processing of collagen; a downstream effect of its role in the collagen-processing complex. Reason: Protein stabilization is a downstream process outcome of PPIB's role in collagen biogenesis; non-core relative to its PPIase function. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt Osteogenesis imperfecta 9 (OI9) |
| GO:0060348 bone development | IMP PMID:20089953 Lack of cyclophilin B in osteogenesis imperfecta with normal... | ACCEPT | Summary: PPIB loss-of-function causes osteogenesis imperfecta type IX; bone development is a genuine, disease-defining biological process for PPIB. Reason: Strongly supported by human genetics - recessive PPIB mutations cause OI9, establishing a core role in collagen biogenesis and bone development. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt Osteogenesis imperfecta 9 (OI9) |
| GO:1901873 regulation of post-translational protein modification | IMP NOT PMID:20089953 Lack of cyclophilin B in osteogenesis imperfecta with normal... | ACCEPT | Summary: A NOT (negated) annotation - PPIB deficiency does not reduce collagen post-translational modification (e.g. prolyl 3-hydroxylation remains normal in the PPIB-null OI), distinguishing it from P3H1/CRTAP loss. Reason: Consistent with the finding that PPIB-null OI shows normal collagen folding/modification; the negation appropriately records that PPIB is not required for regulating this post-translational modification. Supporting Evidence: PMID:20089953 Lack of cyclophilin B in osteogenesis imperfecta with normal collagen folding. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: Exosome proteomics detection (parotid gland); high-throughput localization consistent with a secreted pool. Reason: A proteomic-survey localization; secondary to the core ER-lumen localization. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Exosome proteomics detection (urinary exosomes); same caveat. Reason: A proteomic-survey localization; secondary to the core ER-lumen localization. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0006457 protein folding | IDA PMID:22665516 An interaction map of endoplasmic reticulum chaperones and f... | KEEP AS NON CORE | Summary: PPIB (with ERp72/PDIA4) enhances the rate of IgG folding; protein folding is a downstream process of its PPIase/foldase role. Reason: A valid, directly supported folding-acceleration role, but downstream of the core PPIase molecular function. Supporting Evidence: PMID:22665516 ERp72-cyclophilin B complex that enhances the rate of folding of immunoglobulin |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: Exosome proteomics detection (B-cell exosomes); high-throughput localization. Reason: A proteomic-survey localization; secondary to the core ER-lumen localization. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-1980233 | ACCEPT | Summary: Reactome ER-lumen localization; correct and core. Reason: Consistent with the documented core ER-lumen localization. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-2022073 | ACCEPT | Summary: Reactome ER-lumen localization (collagen biosynthesis pathway); correct and core. Reason: Consistent with the core ER-lumen localization and PPIB's role in collagen biosynthesis. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8948226 | ACCEPT | Summary: Reactome ER-lumen localization; correct and core. Reason: Consistent with the documented core ER-lumen localization. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8948230 | ACCEPT | Summary: Reactome ER-lumen localization; correct and core. Reason: Consistent with the documented core ER-lumen localization. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005515 protein binding | IPI PMID:15095401 Identification of FHOD1-binding proteins and mechanisms of F... | KEEP AS NON CORE | Summary: Interaction captured for PPIB (partner Q9Y613/FHOD1). Bare protein binding is uninformative. Reason: A high-throughput interaction; the generic protein binding term is uninformative and not core. Supporting Evidence: file:human/PPIB/PPIB-goa.tsv UniProtKB:Q9Y613 |
| GO:0003755 peptidyl-prolyl cis-trans isomerase activity | NAS PMID:2000394 Human cyclophilin B: a second cyclophilin gene encodes a pep... | ACCEPT | Summary: The founding characterization describing human cyclophilin B as a peptidyl-prolyl isomerase with a signal sequence. Reason: Supports the core PPIase molecular function from the original gene characterization. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds |
| GO:0005788 endoplasmic reticulum lumen | NAS PMID:1530944 S-cyclophilin is retained intracellularly via a unique COOH-... | ACCEPT | Summary: S-cyclophilin is retained intracellularly via a C-terminal sequence and colocalizes with calreticulin (ER lumen). Reason: Consistent with the core ER-lumen localization and the C-terminal retention motif. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
| GO:0005783 endoplasmic reticulum | TAS PMID:2000394 Human cyclophilin B: a second cyclophilin gene encodes a pep... | ACCEPT | Summary: ER localization asserted in the founding characterization. Reason: TAS-supported ER localization from the original gene description. Supporting Evidence: file:human/PPIB/PPIB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum lumen |
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Download this section (compressed HTML)Q: Given that PPIB-null osteogenesis imperfecta has normal collagen folding, what is the precise non-redundant contribution of PPIB's PPIase activity within the P3H1/CRTAP/PPIB complex versus its scaffolding role?
Q: How is the partitioning of PPIB between its ER foldase pool and its secreted/CD147-signaling pool regulated, and how much do extracellular functions contribute to disease phenotypes?
Experiment: Separate-of-function PPIB mutants (catalytically dead PPIase vs complex-assembly mutants) expressed in PPIB-null cells, assaying collagen 3-hydroxylation, folding kinetics and secretion to dissect catalytic versus scaffolding contributions.
Experiment: Quantify and perturb the secreted/cell-surface cyclophilin B pool (e.g. CD147-blocking) in leukocyte chemotaxis and viral-replication assays to define the in vivo relevance of its extracellular functions.
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