FKBP8 (FKBP38) is a membrane-anchored member of the FKBP immunophilin family. It has a single FKBP-type peptidyl-prolyl cis-trans isomerase (PPIase) domain, three tetratricopeptide (TPR) repeats, and a C-terminal transmembrane helix that anchors it as a tail-anchored, single-pass protein in the mitochondrial outer membrane with its catalytic domain facing the cytoplasm. Unlike other FKBPs, its PPIase activity is constitutively inactive and is switched on by binding calmodulin in a Ca2+-dependent manner. FKBP8 acts as a chaperone that recruits the anti-apoptotic protein BCL2 to mitochondria and modulates its phosphorylation, thereby regulating apoptosis, and it functions as a mitophagy receptor/adaptor that engages BNIP3 and the LC3/GABARAP autophagy machinery to promote selective clearance of mitochondria. It also contributes to chaperone relays (e.g. axonemal dynein assembly), restricts influenza A virus infection, binds HSP90, and has been implicated in mTOR and Hedgehog/Smoothened signaling. It is regulated by PRKN-mediated ubiquitination (degraded during mitophagy) and USP30 deubiquitination.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005829 cytosol | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) annotation of a cytosolic site of action. FKBP8 is a tail-anchored mitochondrial outer-membrane protein with its functional domains facing the cytoplasm/cytosol, so a cytosolic-side site of action is reasonable. Reason: FKBP8's catalytic and TPR domains face the cytosol, but the protein is membrane-anchored; the mitochondrial membrane is the more precise principal localization. Retained as non-core. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt Cytoplasmic side |
| GO:0012505 endomembrane system | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) annotation placing FKBP8 in the endomembrane system, consistent with its membrane-anchored localization (mitochondrial outer membrane and, by transfer, ER membrane). Reason: A generic membrane-system localization; the precise mitochondrial outer-membrane annotation is more informative. Retained as non-core. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0016020 membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) annotation that FKBP8 acts at a membrane, consistent with its C-terminal transmembrane anchor. Reason: Correct but generic; the mitochondrial outer-membrane annotation is the more precise localization. Retained as non-core. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt Single-pass membrane protein |
| GO:0005740 mitochondrial envelope | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) annotation placing FKBP8 in the mitochondrial envelope, consistent with its experimentally documented mitochondrial outer-membrane localization. Reason: FKBP8 is a tail-anchored mitochondrial outer-membrane (envelope) protein; this localization is experimentally supported and is the principal site of action. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0006457 protein folding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) annotation of protein folding. FKBP8 has a (conditionally active) PPIase domain and chaperone activity; the molecular function (chaperone / PPIase) is more informative. Reason: A downstream/contributory process; the chaperone and PPIase molecular functions are the core. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt Seems to act as a chaperone for BCL2 |
| GO:0043066 negative regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: FKBP8 chaperones the anti-apoptotic protein BCL2 to mitochondria and modulates its phosphorylation; its active form regulates apoptosis. A plausible biological process for FKBP8. Reason: FKBP8 modulates apoptosis via BCL2, but the effect can be context-dependent (the BCL2/FKBP8/CaM complex can interfere with BCL2 target binding); retained as a non-core process. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt The active form of FKBP8 may therefore play a role in the regulation of apoptosis. |
| GO:0044183 protein folding chaperone | IBA GO_REF:0000033 | ACCEPT | Summary: FKBP8 acts as a chaperone (e.g. for BCL2 and in chaperone relays such as axonemal dynein assembly). A core molecular function. Reason: Chaperone function is experimentally supported (BCL2 chaperone; ZMYND10/dynein chaperone relay, IMP PMID:29916806) and inferred phylogenetically; core to FKBP8. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt Seems to act as a chaperone for BCL2 |
| GO:0003755 peptidyl-prolyl cis-trans isomerase activity | IEA GO_REF:0000120 | ACCEPT | Summary: FKBP8 has an FKBP-type PPIase domain (EC 5.2.1.8), but the activity is constitutively inactive and only switched on by calmodulin/Ca2+ binding. A conditional core molecular function. Reason: PPIase activity is documented (EC 5.2.1.8; PubMed:15990872) but is Ca2+/calmodulin-dependent; the IEA correctly reflects the catalytic capacity of the FKBP domain. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt Constitutively inactive PPiase, which becomes active when bound to calmodulin and calcium. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation of mitochondrial localization, consistent with the experimentally documented mitochondrial outer-membrane localization. Reason: Correct principal localization; agrees with EXP/IDA evidence. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0007165 signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Generic electronic annotation of signal transduction. FKBP8 has documented signaling roles (mTOR inhibition, Hedgehog/Smoothened, anti-viral), but the term is non-specific. Reason: A generic process term; FKBP8's specific signaling roles are better captured elsewhere. Retained as non-core. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0007165 signal transduction IEA GO_REF:0000117 |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation of mitochondrial membrane localization, consistent with FKBP8's tail-anchored mitochondrial outer-membrane localization. Reason: Correct principal localization (single-pass mitochondrial outer-membrane protein); agrees with EXP evidence. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt Mitochondrion membrane |
| GO:0005515 protein binding | IPI PMID:16844119 Hepatitis C virus non-structural protein NS5A interacts with... | KEEP AS NON CORE | Summary: Interaction with hepatitis C virus NS5A (O39474). Bare protein binding is uninformative; a microbial-infection interaction. Reason: A real virus-host interaction documented in UniProt, but recorded as bare protein binding and peripheral to the core function. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt Interacts with hepatitis C/HCV protein NS5A. |
| GO:0005515 protein binding | IPI PMID:17024179 Hepatitis C virus RNA replication is regulated by FKBP8 and ... | MODIFY | Summary: IntAct interactions with HCV NS5A (O39474) and HSP90AA1 (P07900). Bare protein binding is uninformative; the HSP90 interaction is the most informative. Reason: Bare protein binding is uninformative; the WITH partner HSP90AA1 makes Hsp90 protein binding (GO:0051879) the precise function. Proposed replacements: Hsp90 protein binding Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005515 protein binding IPI PMID:17024179 UniProtKB:P07900 |
| GO:0005515 protein binding | IPI PMID:17082457 Protrudin induces neurite formation by directional membrane ... | KEEP AS NON CORE | Summary: IntAct interaction with ZFYVE27/protrudin (Q5T4F4). Bare protein binding is uninformative; FKBP8 may negatively regulate ZFYVE27 phosphorylation. Reason: A real, specific interaction (ZFYVE27) documented in UniProt, but recorded as bare protein binding and not the core function. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt Interacts with ZFYVE27 |
| GO:0005515 protein binding | IPI PMID:17353276 The peptidyl prolyl cis/trans isomerase FKBP38 determines hy... | KEEP AS NON CORE | Summary: IntAct interaction with EGLN1/PHD2 (Q9GZT9). Bare protein binding is uninformative; an isolated interactome hit. Reason: An isolated interaction recorded as bare protein binding; uninformative and not core. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005515 protein binding IPI PMID:17353276 UniProtKB:Q9GZT9 |
| GO:0005515 protein binding | IPI PMID:18216108 A single-amino-acid mutation in hepatitis C virus NS5A disru... | KEEP AS NON CORE | Summary: IntAct interaction with a viral protein (Q9WMX2 processed chain). Bare protein binding is uninformative; a virus-host interaction. Reason: A virus-host interaction recorded as bare protein binding; not part of the core function. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005515 protein binding IPI PMID:18216108 UniProtKB:Q9WMX2-PRO_0000037551 |
| GO:0005515 protein binding | IPI PMID:18459960 Regulation of apoptosis and neurite extension by FKBP38 is r... | KEEP AS NON CORE | Summary: IntAct interaction with ZFYVE27/protrudin (Q5T4F4). Bare protein binding is uninformative. Reason: A real, specific interaction (ZFYVE27) recorded as bare protein binding; not the core function. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt Interacts with ZFYVE27 |
| GO:0005515 protein binding | IPI PMID:20029029 Regulation of epidermal growth factor receptor trafficking b... | KEEP AS NON CORE | Summary: IntAct interaction with EGFR (P00533). Bare protein binding is uninformative; an isolated interactome hit. Reason: An isolated interaction recorded as bare protein binding; uninformative and not core. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005515 protein binding IPI PMID:20029029 UniProtKB:P00533 |
| GO:0005515 protein binding | IPI PMID:21360678 Label-free quantitative proteomics and SAINT analysis enable... | MODIFY | Summary: IntAct interaction with HSP90AA1 (P07900). Bare protein binding is uninformative; the partner is HSP90. Reason: Bare protein binding is uninformative; the WITH partner is HSP90AA1, so Hsp90 protein binding (GO:0051879) is the precise function. Proposed replacements: Hsp90 protein binding Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005515 protein binding IPI PMID:21360678 UniProtKB:P07900 |
| GO:0005515 protein binding | IPI PMID:24169621 Elucidating novel hepatitis C virus-host interactions using ... | KEEP AS NON CORE | Summary: IntAct interaction with a viral protein (Q9WMX2 processed chain). Bare protein binding is uninformative; a virus-host interaction. Reason: A virus-host interaction recorded as bare protein binding; not part of the core function. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005515 protein binding IPI PMID:24169621 UniProtKB:Q9WMX2-PRO_0000037551 |
| GO:0005515 protein binding | IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc... | MODIFY | Summary: Quantitative chaperone interaction network (Taipale et al.) capturing FKBP8-HSP90AB1 (P08238). Bare protein binding is uninformative; the partner is HSP90. Reason: Bare protein binding is uninformative; the WITH partner is HSP90AB1, so Hsp90 protein binding (GO:0051879) is the precise function. Proposed replacements: Hsp90 protein binding Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005515 protein binding IPI PMID:25036637 UniProtKB:P08238 |
| GO:0005515 protein binding | IPI PMID:26567527 Involvement of FKBP6 in hepatitis C virus replication. | KEEP AS NON CORE | Summary: IntAct interactions with FKBP6 (O75344) and a viral protein. Bare protein binding is uninformative. Reason: Real interactions recorded as bare protein binding; not individually core. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005515 protein binding IPI PMID:26567527 UniProtKB:O75344 |
| GO:0005515 protein binding | IPI PMID:28169297 Comparative influenza protein interactomes identify the role... | KEEP AS NON CORE | Summary: IntAct interactions with influenza A virus PB1 proteins (P03431, Q5EP37). Bare protein binding is uninformative; FKBP8 restricts influenza A virus infection. Reason: A real virus-host interaction (IAV PB1) recorded as bare protein binding; relevant to FKBP8's anti-viral role but not a core MF annotation. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005515 protein binding IPI PMID:28169297 UniProtKB:P03431 |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | KEEP AS NON CORE | Summary: IntAct interaction with EGFR (P00533). Bare protein binding is uninformative; an isolated interactome hit. Reason: An isolated interaction recorded as bare protein binding; uninformative and not core. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005515 protein binding IPI PMID:31980649 UniProtKB:P00533 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: A large membrane-protein interactome screen reporting ~25 FKBP8 partners, almost all single-pass transmembrane/membrane proteins. Bare protein binding from a broad screen of a membrane-anchored bait is uninformative. Reason: Bare protein binding from one high-throughput membrane-interactome screen with many partners not independently validated; uninformative and not reflective of the core function. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005515 protein binding IPI PMID:32296183 UniProtKB:P10415 |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: A high-throughput screen capturing FKBP8 with HSP90AA1/AB1 (P07900/P08238). The HSP90 interactions are the most informative. Reason: Bare protein binding is uninformative; the partners include HSP90AA1/AB1, so Hsp90 protein binding (GO:0051879) is appropriate. Proposed replacements: Hsp90 protein binding Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005515 protein binding IPI PMID:35271311 UniProtKB:P07900 |
| GO:0042802 identical protein binding | IPI PMID:17024179 Hepatitis C virus RNA replication is regulated by FKBP8 and ... | KEEP AS NON CORE | Summary: FKBP8 self-interaction (Q14318-Q14318), consistent with the documented ability to form homomultimers. Reason: A real self-association (homomultimer), but a generic binding term peripheral to FKBP8's core chaperone/PPIase function. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt Homomultimers or heteromultimers |
| GO:0005740 mitochondrial envelope | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic annotation (from mouse O35465) of mitochondrial envelope localization, consistent with the experimentally documented mitochondrial outer-membrane localization. Reason: Correct principal localization; agrees with EXP/IDA evidence. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic annotation (from mouse O35465) of ER membrane localization. A secondary membrane compartment for this tail-anchored protein, not the principal characterized location. Reason: Plausible secondary localization of a tail-anchored protein, transferred electronically from mouse; the mitochondrial outer membrane is the principal site. Retained as non-core. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005789 endoplasmic reticulum membrane IEA GO_REF:0000107 UniProtKB:O35465 |
| GO:0044183 protein folding chaperone | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation (from mouse O35465) of chaperone activity, consistent with the experimentally documented chaperone function (BCL2 chaperone; dynein assembly relay). Reason: Agrees with experimental chaperone evidence; a core molecular function. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt Seems to act as a chaperone for BCL2 |
| GO:0005515 protein binding | IPI PMID:32686675 PDZD8 interacts with Protrudin and Rab7 at ER-late endosome ... | KEEP AS NON CORE | Summary: IntAct interaction (Q8NEN9/DIP2B). Bare protein binding is uninformative; an isolated interactome hit. Reason: An isolated interaction recorded as bare protein binding; uninformative and not core. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005515 protein binding IPI PMID:32686675 UniProtKB:Q8NEN9 |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: Direct immunofluorescence (HPA) evidence for mitochondrial localization, the principal site of FKBP8 action. Reason: IDA-supported mitochondrial localization agrees with the documented principal site. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005739 mitochondrion IDA GO_REF:0000052 |
| GO:0005739 mitochondrion | EXP PMID:16176796 Molecular characterization of FK-506 binding protein 38 and ... | ACCEPT | Summary: Experimental evidence for mitochondrial localization of FKBP8. Reason: Directly experimentally supported principal localization. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0031966 mitochondrial membrane | EXP PMID:12510191 Inherent calcineurin inhibitor FKBP38 targets Bcl-2 to mitoc... | ACCEPT | Summary: Experimental evidence for FKBP8 localization to the mitochondrial membrane (single-pass, cytoplasmic side). Reason: Directly experimentally supported principal localization as a tail-anchored mitochondrial outer-membrane protein. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt Mitochondrion membrane |
| GO:0031966 mitochondrial membrane | EXP PMID:18385096 Characterization of a Bcl-XL-interacting protein FKBP8 and i... | ACCEPT | Summary: Experimental evidence (isoform-resolved) for FKBP8 localization to the mitochondrial membrane. Reason: Directly experimentally supported principal localization. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt Mitochondrion membrane |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-throughput evidence for mitochondrial localization, consistent with the principal site of FKBP8 action. Reason: Consistent with strong EXP/IDA evidence for mitochondrial localization. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:1901524 regulation of mitophagy | IDA PMID:28381481 FKBP8 recruits LC3A to mediate Parkin-independent mitophagy. | ACCEPT | Summary: Direct evidence that FKBP8 regulates mitophagy, acting as a mitophagy receptor/adaptor that engages BNIP3 and the LC3/GABARAP autophagy machinery. A core biological process. Reason: Directly demonstrated (IDA) role in regulation of mitophagy; FKBP8 is a recognized mitophagy receptor. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:1901524 regulation of mitophagy IDA PMID:28381481 |
| GO:1901524 regulation of mitophagy | IDA PMID:31908024 FKBP8 LIRL-dependent mitochondrial fragmentation facilitates... | ACCEPT | Summary: Second direct demonstration that FKBP8 regulates mitophagy. A core biological process. Reason: Independently corroborated (IDA) role in regulation of mitophagy. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:1901524 regulation of mitophagy IDA PMID:31908024 |
| GO:0070585 protein localization to mitochondrion | IPI PMID:31908024 FKBP8 LIRL-dependent mitochondrial fragmentation facilitates... | ACCEPT | Summary: FKBP8 promotes protein localization to mitochondria (WITH partner BNIP3, Q9GZQ8), consistent with its mitophagy-receptor/adaptor role. Reason: Supported by direct interaction evidence; consistent with FKBP8's documented role in targeting proteins (e.g. BCL2, BNIP3) to mitochondria. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0070585 protein localization to mitochondrion IPI PMID:31908024 UniProtKB:Q9GZQ8 |
| GO:0005515 protein binding | IPI PMID:28381481 FKBP8 recruits LC3A to mediate Parkin-independent mitophagy. | KEEP AS NON CORE | Summary: IntAct interactions with autophagy LC3/GABARAP family proteins and BNIP3 (Q9GZQ8), underlying FKBP8's mitophagy-receptor function. Bare protein binding is uninformative. Reason: Real, biologically meaningful interactions (autophagy machinery/BNIP3), but recorded as bare protein binding; the mitophagy function is captured by the dedicated process terms. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005515 protein binding IPI PMID:28381481 UniProtKB:O95166 |
| GO:0005515 protein binding | IPI PMID:31908024 FKBP8 LIRL-dependent mitochondrial fragmentation facilitates... | KEEP AS NON CORE | Summary: IntAct interaction with BNIP3 (Q9GZQ8), underlying FKBP8's mitophagy-receptor function. Bare protein binding is uninformative. Reason: A real, biologically meaningful interaction (BNIP3) recorded as bare protein binding; the mitophagy function is captured by the dedicated process terms. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005515 protein binding IPI PMID:31908024 UniProtKB:Q9GZQ8 |
| GO:0005516 calmodulin binding | EXP PMID:20707607 New structural aspects of FKBP38 activation. | ACCEPT | Summary: FKBP8 binds calmodulin; calmodulin/Ca2+ binding activates its otherwise-inactive PPIase domain. A core molecular function. Reason: Calmodulin binding is experimentally demonstrated and is the switch that activates FKBP8's catalytic and BCL2-chaperone activity; central to its regulation. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt Forms heterodimer with calmodulin. |
| GO:0005516 calmodulin binding | IPI PMID:24145868 Functional role of the flexible N-terminal extension of FKBP... | ACCEPT | Summary: Interaction with calmodulin (P0DP23) confirmed by IPI. A core molecular function. Reason: Calmodulin binding is the activating interaction for FKBP8's PPIase and chaperone activities. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005516 calmodulin binding IPI PMID:24145868 UniProtKB:P0DP23 |
| GO:0005516 calmodulin binding | EXP PMID:24145868 Functional role of the flexible N-terminal extension of FKBP... | ACCEPT | Summary: Experimental confirmation of FKBP8-calmodulin binding. A core molecular function. Reason: Independently corroborates the activating calmodulin interaction. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt Forms heterodimer with calmodulin. |
| GO:0006457 protein folding | IMP PMID:29916806 ZMYND10 functions in a chaperone relay during axonemal dynei... | KEEP AS NON CORE | Summary: FKBP8 functions in a chaperone relay during axonemal dynein assembly (ZMYND10 study). The chaperone molecular function is the more informative annotation; folding is the process context. Reason: A genuine chaperone-relay folding role (IMP), but the chaperone MF is the core; folding is retained as a non-core process. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0006457 protein folding IMP PMID:29916806 |
| GO:0044183 protein folding chaperone | IMP PMID:29916806 ZMYND10 functions in a chaperone relay during axonemal dynei... | ACCEPT | Summary: FKBP8 acts as a chaperone in the ZMYND10-dependent chaperone relay for axonemal dynein assembly (IMP). A core molecular function. Reason: Mutant-phenotype evidence supports FKBP8's chaperone function in dynein assembly, corroborating the chaperone MF. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0044183 protein folding chaperone IMP PMID:29916806 |
| GO:0001933 negative regulation of protein phosphorylation | IMP PMID:15733859 The flexible loop of Bcl-2 is required for molecular interac... | KEEP AS NON CORE | Summary: FKBP8 modulates the phosphorylation state of BCL2 (and ZFYVE27); the BCL2 flexible loop mediates the FKBP8 interaction. A plausible process linked to its chaperone role. Reason: A real but specialized process (BCL2 phospho modulation); retained as non-core relative to the core chaperone/mitophagy functions. Supporting Evidence: PMID:15733859 flexible loop of Bcl-2 is required for molecular interaction |
| GO:0032991 protein-containing complex | IMP PMID:15733859 The flexible loop of Bcl-2 is required for molecular interac... | KEEP AS NON CORE | Summary: FKBP8 is part of a BCL2-containing complex (BCL2/FKBP8/calmodulin/Ca2+). A generic complex-membership annotation. Reason: A generic protein-complex term; the specific BCL2/calmodulin interactions are captured elsewhere. Retained as non-core. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt The BCL2/FKBP8/calmodulin/calcium complex probably interferes with the binding of BCL2 to its targets. |
| GO:0097718 disordered domain specific binding | IPI PMID:15733859 The flexible loop of Bcl-2 is required for molecular interac... | ACCEPT | Summary: FKBP8 binds the disordered flexible loop of BCL2 (P10415). A specific molecular function capturing the BCL2-chaperone interaction mode. Reason: Directly supported (IPI) binding to the disordered flexible loop of BCL2; an informative molecular function underlying the BCL2-chaperone role. Supporting Evidence: PMID:15733859 flexible loop of Bcl-2 is required for molecular interaction |
| GO:0005515 protein binding | IPI PMID:18160438 Human butyrate-induced transcript 1 interacts with hepatitis... | KEEP AS NON CORE | Summary: IntAct interaction (Q9P035/HACD3). Bare protein binding is uninformative; an isolated interactome hit. Reason: An isolated interaction recorded as bare protein binding; uninformative and not core. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0005515 protein binding IPI PMID:18160438 UniProtKB:Q9P035 |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: High-throughput proteomic detection of FKBP8 in a membrane fraction, consistent with its membrane-anchored nature. Reason: A generic membrane localization from proteomics; the mitochondrial outer-membrane annotation is more precise. Retained as non-core. Supporting Evidence: file:human/FKBP8/FKBP8-uniprot.txt Single-pass membrane protein |
| GO:0035556 intracellular signal transduction | TAS PMID:10197430 muFKBP38: a novel murine immunophilin homolog differentially... | KEEP AS NON CORE | Summary: Author-stated involvement in intracellular signal transduction. FKBP8 has documented signaling roles (mTOR, Hedgehog), but the term is non-specific. Reason: A generic signaling process term; FKBP8's specific signaling roles are better captured elsewhere. Retained as non-core. Supporting Evidence: file:human/FKBP8/FKBP8-goa.tsv GO:0035556 intracellular signal transduction TAS PMID:10197430 |
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Download this section (compressed HTML)Q: Is FKBP8's Ca2+/calmodulin-activated PPIase catalytic activity required for its BCL2-chaperone and mitophagy-receptor functions, or are these adaptor roles catalysis-independent?
Q: How is FKBP8's dual role as an anti-apoptotic BCL2 chaperone reconciled with its pro-mitophagy receptor function at the same mitochondrial outer membrane?
Q: What determines the partitioning of FKBP8 between the mitochondrial outer membrane and the ER membrane, and does the ER pool have a distinct function?
Experiment: Test PPIase-dead and calmodulin-binding-deficient FKBP8 mutants for BCL2 mitochondrial targeting, BCL2 phosphorylation, and mitophagy induction to separate catalytic from adaptor contributions.
Experiment: Use FKBP8 knockout/knockdown with BNIP3- and PRKN-dependent mitophagy reporters to define its role as a mitophagy receptor and its regulation by USP30/PRKN ubiquitination.
Experiment: Map the FKBP8 interactome by compartment-resolved proximity labeling to distinguish bona fide functional partners (BCL2, BNIP3, calmodulin, HSP90, LC3/GABARAP) from co-fractionating membrane proteins in high-throughput screens.
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