Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:1990756 ubiquitin-like ligase-substrate adaptor activity	IDA PMID:25778398 The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial...	NEW	Summary: Proposed core molecular function. As the F-box/LRR substrate-recognition subunit of SCF(FBXL7), FBXL7 selects substrates (AURKA, survivin/BIRC5) for SCF-dependent polyubiquitination. This more informative MF term is not in the GOA, which lacks any explicit MF annotation for FBXL7. Reason: Captures the precise molecular function of FBXL7 as an SCF substrate-recognition adaptor, more informative than the bare protein binding annotations and absent from the existing GOA. Supporting Evidence: PMID:25778398 Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin by interacting with Glu-126 within its carboxyl-terminal α helix
GO:0005813 centrosome	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated electronic assignment of centrosome localization, where FBXL7 acts during spindle formation. Core localization for its mitotic role. Reason: Core localization; FBXL7 localizes to the centrosome during spindle formation, consistent with its mitotic substrate-targeting role. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	Summary: Binary interactome reference map interactions. Bare protein binding is uninformative. Reason: High-throughput interactome; bare protein binding is uninformative per curation guidelines. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Q9UJT9; Q92609: TBC1D5; NbExp=3; IntAct=EBI-914660, EBI-742381
GO:0000086 G2/M transition of mitotic cell cycle	IEA GO_REF:0000107	ACCEPT	Summary: Ortholog-based electronic assignment of involvement in the G2/M transition, consistent with FBXL7-driven AURKA degradation and mitotic arrest. Reason: Core biological process; FBXL7 regulates mitotic progression (mitotic arrest via AURKA degradation). Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA, causing mitotic arrest
GO:0000209 protein polyubiquitination	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated electronic assignment of protein polyubiquitination, the specific modification FBXL7 directs onto its substrates. Reason: Correct; FBXL7 mediates substrate polyubiquitination, supported by IDA/IMP evidence (survivin). Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt regulates mitochondrial function by mediating the ubiquitination and proteasomal degradation of the apoptosis inhibitor BIRC5
GO:0000278 mitotic cell cycle	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-based electronic assignment of involvement in the mitotic cell cycle, consistent with FBXL7's role in mitotic regulation. Reason: Correct but generic relative to the specific G2/M transition and SCF-dependent degradation annotations. Supporting Evidence: PMID:25778398 Fbxl7, a component of the Skp1·Cul1·F-box protein type ubiquitin E3 ligase, regulates mitotic cell cycle progression
GO:0016567 protein ubiquitination	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Combined automated electronic assignment of protein ubiquitination, a parent of the specific SCF-dependent polyubiquitination FBXL7 mediates. Reason: Correct but generic; the specific SCF-dependent catabolic / polyubiquitination annotations better capture the role. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt PATHWAY: Protein modification; protein ubiquitination.
GO:0019005 SCF ubiquitin ligase complex	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated electronic assignment of SCF complex membership, the core assembly context for FBXL7. Reason: Core cellular component; redundant with IDA/ISS evidence. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL7) composed of CUL1, SKP1, RBX1 and FBXL7
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated electronic assignment of SCF-dependent proteasomal degradation, the core biological process of SCF(FBXL7). Reason: Core biological process; redundant with the experimental IDA/IMP evidence (survivin/AURKA degradation). Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt regulates mitochondrial function by mediating the ubiquitination and proteasomal degradation of the apoptosis inhibitor BIRC5
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	NAS PMID:33234069 The FBXL family of F-box proteins: variations on a theme.	ACCEPT	Summary: Author-statement (FBXL family review) assignment of the core SCF-dependent proteasomal degradation process. Reason: Core biological process; consistent with the experimental substrate-degradation evidence. Supporting Evidence: PMID:25778398 Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin
GO:0042981 regulation of apoptotic process	NAS PMID:25654763 F-box protein Fbxl18 mediates polyubiquitylation and proteas...	ACCEPT	Summary: Author-statement (ComplexPortal) assignment of regulation of apoptosis; FBXL7 is a proapoptotic factor and its degradation of survivin/BIRC5 promotes apoptosis. Reason: Supported biological process; FBXL7 is proapoptotic and regulates apoptosis via degradation of the IAP survivin/BIRC5. Supporting Evidence: PMID:25654763 Fbxl18 regulates apoptosis by mediating ubiquitin-dependent proteasomal degradation of the pro-apoptotic protein Fbxl7
GO:0000209 protein polyubiquitination	IMP PMID:28218735 Aurora kinase A regulates Survivin stability through targeti...	ACCEPT	Summary: Mutant-phenotype evidence that FBXL7 mediates polyubiquitination of BIRC5/survivin. Core activity. Reason: Directly supported substrate polyubiquitination (survivin/BIRC5); consistent with FBXL7's SCF substrate-receptor function. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt this interaction allows BIRC5 to be polyubiquitinated by the SCF(FBXL7) E3 ubiquitin-protein ligase complex
GO:0005515 protein binding	IPI PMID:28218735 Aurora kinase A regulates Survivin stability through targeti...	KEEP AS NON CORE	Summary: Interaction with BIRC5/survivin (a FBXL7 substrate). Bare protein binding is uninformative. Reason: Records the functionally important FBXL7-BIRC5 substrate interaction but bare protein binding is uninformative. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Interacts with BIRC5; this interaction allows BIRC5 to be polyubiquitinated by the SCF(FBXL7)
GO:0019005 SCF ubiquitin ligase complex	IDA PMID:25778398 The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial...	ACCEPT	Summary: Direct evidence that FBXL7 is a component of the SCF (SKP1-CUL1-F-box) E3 ligase complex. Core cellular component. Reason: Core cellular component; FBXL7 is the F-box substrate receptor of the SCF(FBXL7) complex. Supporting Evidence: PMID:25778398 Fbxl7, a component of the Skp1·Cul1·F-box protein type ubiquitin E3 ligase, regulates mitotic cell cycle progression
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	IDA PMID:25778398 The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial...	ACCEPT	Summary: Direct evidence that SCF(FBXL7) drives proteasomal degradation of survivin/BIRC5. Core biological process. Reason: Core biological process directly demonstrated; FBXL7 targets survivin for SCF-dependent proteasomal degradation. Supporting Evidence: PMID:25778398 Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	IMP PMID:28218735 Aurora kinase A regulates Survivin stability through targeti...	ACCEPT	Summary: Mutant-phenotype evidence linking FBXL7 to SCF-dependent degradation of survivin in the AURKA/gastric-cancer study. Core biological process. Reason: Core biological process; FBXL7 mediates proteasomal degradation of survivin/BIRC5. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt regulates mitochondrial function by mediating the ubiquitination and proteasomal degradation of the apoptosis inhibitor BIRC5
GO:0000209 protein polyubiquitination	IDA PMID:25778398 The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial...	ACCEPT	Summary: Direct evidence that FBXL7 polyubiquitinates survivin (at Lys90/Lys91). Core activity. Reason: Directly demonstrated substrate polyubiquitination of survivin/BIRC5. Supporting Evidence: PMID:25778398 Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin
GO:0005515 protein binding	IPI PMID:25778398 The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial...	KEEP AS NON CORE	Summary: Interaction with survivin (via Glu-126 in its C-terminal helix). Bare protein binding is uninformative. Reason: Records the functionally important FBXL7-survivin substrate interaction but bare protein binding is uninformative. Supporting Evidence: PMID:25778398 Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin by interacting with Glu-126 within its carboxyl-terminal α helix
GO:0005829 cytosol	TAS Reactome:R-HSA-8854051	KEEP AS NON CORE	Summary: Reactome curation of cytosolic localization (SCF-FBXL18 ubiquitinates FBXL7). Consistent with the cytoplasmic site of action. Reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome during spindle formation. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol	TAS Reactome:R-HSA-8854071	KEEP AS NON CORE	Summary: Reactome curation of cytosolic localization (proteasome-mediated degradation of PolyUb-FBXL7). Consistent with the cytoplasmic site of action. Reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol	TAS Reactome:R-HSA-8853496	KEEP AS NON CORE	Summary: Reactome curation of cytosolic localization (SCF:FBXL7 binds AURKA). Consistent with the cytoplasmic site of action. Reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA
GO:0005829 cytosol	TAS Reactome:R-HSA-8854041	KEEP AS NON CORE	Summary: Reactome curation of cytosolic localization (SCF-FBXL7 ubiquitinates AURKA). Consistent with the cytoplasmic site of action. Reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA
GO:0005829 cytosol	TAS Reactome:R-HSA-8854044	KEEP AS NON CORE	Summary: Reactome curation of cytosolic localization (proteasome degrades AURKA ubiquitinated by SCF-FBXL7). Consistent with the cytoplasmic site of action. Reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA
GO:0005829 cytosol	TAS Reactome:R-HSA-8854052	KEEP AS NON CORE	Summary: Reactome curation of cytosolic localization (formation of the SCF-FBXL7 complex). Consistent with the cytoplasmic site of action. Reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL7) composed of CUL1, SKP1, RBX1 and FBXL7
GO:0005829 cytosol	TAS Reactome:R-HSA-8952618	KEEP AS NON CORE	Summary: Reactome curation of cytosolic localization (neddylation of CRL1). Generic CRL-pathway localization. Reason: Correct cytoplasmic compartment but from generic CRL neddylation-pathway context; the functionally salient localization is the centrosome. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol	TAS Reactome:R-HSA-8952620	KEEP AS NON CORE	Summary: Reactome curation of cytosolic localization (NEDD8:UBE2M binds CRL1). Generic CRL-pathway localization. Reason: Correct cytoplasmic compartment but from generic CRL-pathway context; redundant. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol	TAS Reactome:R-HSA-8955241	KEEP AS NON CORE	Summary: Reactome curation of cytosolic localization (CAND1 binds cytosolic CRL). Generic CRL-pathway localization. Reason: Correct cytoplasmic compartment but from generic CRL-regulation pathway context; redundant. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol	TAS Reactome:R-HSA-8955289	KEEP AS NON CORE	Summary: Reactome curation of cytosolic localization (COMMDs displace CAND1). Generic CRL-pathway localization. Reason: Correct cytoplasmic compartment but from generic CRL-regulation pathway context; redundant. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol	TAS Reactome:R-HSA-8956040	KEEP AS NON CORE	Summary: Reactome curation of cytosolic localization (COP9 signalosome deneddylates CRL). Generic CRL-pathway localization. Reason: Correct cytoplasmic compartment but from generic CRL-regulation pathway context; redundant. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol	TAS Reactome:R-HSA-8956200	KEEP AS NON CORE	Summary: Reactome curation of cytosolic localization (DCUN1D3 binds CRL1). Generic CRL-pathway localization. Reason: Correct cytoplasmic compartment but from generic CRL-regulation pathway context; redundant. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol	TAS Reactome:R-HSA-983140	KEEP AS NON CORE	Summary: Reactome curation of cytosolic localization (transfer of Ub from E2 to substrate). Generic ubiquitination-pathway localization. Reason: Correct cytoplasmic compartment but from generic ubiquitination-pathway context; redundant. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol	TAS Reactome:R-HSA-983147	KEEP AS NON CORE	Summary: Reactome curation of cytosolic localization (release of E3 from polyubiquitinated substrate). Generic ubiquitination-pathway localization. Reason: Correct cytoplasmic compartment but from generic ubiquitination-pathway context; redundant. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol	TAS Reactome:R-HSA-983156	KEEP AS NON CORE	Summary: Reactome curation of cytosolic localization (polyubiquitination of substrate). Generic ubiquitination-pathway localization. Reason: Correct cytoplasmic compartment but from generic ubiquitination-pathway context; redundant. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol	TAS Reactome:R-HSA-983157	KEEP AS NON CORE	Summary: Reactome curation of cytosolic localization (interaction of E3 with substrate and E2-Ub). Generic ubiquitination-pathway localization. Reason: Correct cytoplasmic compartment but from generic ubiquitination-pathway context; redundant. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0000086 G2/M transition of mitotic cell cycle	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity assignment of involvement in the G2/M transition, consistent with FBXL7-driven AURKA degradation. Reason: Core biological process; FBXL7 regulates the mitotic G2/M transition. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA, causing mitotic arrest
GO:0000278 mitotic cell cycle	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity assignment of involvement in the mitotic cell cycle. Reason: Correct but generic relative to the specific G2/M transition annotation. Supporting Evidence: PMID:25778398 Fbxl7, a component of the Skp1·Cul1·F-box protein type ubiquitin E3 ligase, regulates mitotic cell cycle progression
GO:0005813 centrosome	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity assignment of centrosome localization, where FBXL7 acts during spindle formation. Core localization. Reason: Core localization; FBXL7 localizes to the centrosome during spindle formation. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Localizes to the centrosome during spindle formation.
GO:0016567 protein ubiquitination	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity assignment of protein ubiquitination, a parent of the specific SCF-dependent polyubiquitination FBXL7 mediates. Reason: Correct but generic; the specific polyubiquitination/SCF-dependent catabolic annotations better capture the role. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt PATHWAY: Protein modification; protein ubiquitination.
GO:0019005 SCF ubiquitin ligase complex	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity assignment of SCF complex membership, the core assembly context for FBXL7. Reason: Core cellular component; redundant with IDA/IEA evidence. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL7) composed of CUL1, SKP1, RBX1 and FBXL7
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity assignment of SCF-dependent proteasomal degradation, the core biological process of SCF(FBXL7). Reason: Core biological process; redundant with the experimental IDA/IMP evidence. Supporting Evidence: PMID:25778398 Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin
GO:0000151 ubiquitin ligase complex	NAS PMID:10531035 Identification of a family of human F-box proteins.	KEEP AS NON CORE	Summary: Author-statement assignment (original F-box family paper) of being part of a ubiquitin ligase complex. A generic parent of the specific SCF complex. Reason: Correct but generic; subsumed by the specific SCF ubiquitin ligase complex annotation. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL7)
GO:0006511 ubiquitin-dependent protein catabolic process	NAS PMID:10531035 Identification of a family of human F-box proteins.	KEEP AS NON CORE	Summary: Author-statement assignment of ubiquitin-dependent protein catabolism, a parent of the specific SCF-dependent proteasomal degradation FBXL7 mediates. Reason: Correct but generic; the specific GO:0031146 (SCF-dependent proteasomal catabolic process) better captures the role. Supporting Evidence: file:human/FBXL7/FBXL7-uniprot.txt regulates mitochondrial function by mediating the ubiquitination and proteasomal degradation of the apoptosis inhibitor BIRC5

Core Functions

Functions as the substrate-recognition (F-box) subunit of an SCF (SKP1-CUL1-RBX1-FBXL7) cullin-RING E3 ubiquitin ligase that recruits the mitotic kinase Aurora A (AURKA) during mitosis for polyubiquitination and proteasomal degradation, contributing to control of the G2/M transition and mitotic progression.

Molecular Function:

ubiquitin-like ligase-substrate adaptor activity

Directly Involved In:

G2/M transition of mitotic cell cycle SCF-dependent proteasomal ubiquitin-dependent protein catabolic process

Cellular Locations:

centrosome

Supporting Evidence:

file:human/FBXL7/FBXL7-uniprot.txt
During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA, causing mitotic arrest

As the SCF(FBXL7) substrate receptor, binds the inhibitor-of-apoptosis protein survivin/BIRC5 and directs its polyubiquitination and proteasomal degradation, thereby regulating mitochondrial function and promoting apoptosis.

Molecular Function:

ubiquitin-like ligase-substrate adaptor activity

Directly Involved In:

SCF-dependent proteasomal ubiquitin-dependent protein catabolic process regulation of apoptotic process

Cellular Locations:

cytosol

Supporting Evidence:

PMID:25778398
Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin

As the SCF(FBXL7) substrate receptor, recognizes and directs the polyubiquitination and proteasomal degradation of additional substrates that drive epithelial-mesenchymal transition and metabolic reprogramming - active c-SRC (after Ser104 phosphorylation), the EMT transcription factor SNAI1/Snail1, and the glycolytic enzyme PFKFB4 - acting in cancer as a metastasis suppressor whose loss (via promoter hypermethylation or hypoxia/EZH2-driven transcriptional repression) promotes invasion and glycolysis. (Substrates beyond AURKA/survivin are reported in primary cancer literature summarized by the Falcon deep-research report and are not yet in the curated GOA.)

Molecular Function:

ubiquitin-like ligase-substrate adaptor activity

Directly Involved In:

SCF-dependent proteasomal ubiquitin-dependent protein catabolic process

Cellular Locations:

cytosol

Supporting Evidence:

file:human/FBXL7/FBXL7-deep-research-falcon.md
A high-impact cancer epigenetics study established FBXL7 as a **metastasis-suppressor axis component** through control of **active c-SRC**: FBXL7 mediates **ubiquitylation and proteasomal degradation of active c-SRC after phosphorylation at Ser104**, and loss of FBXL7 promotes EMT and metastasis.

References

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10531035

Identification of a family of human F-box proteins.

PMID:25654763

F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7.

FBXL7 is a proapoptotic SCF subunit that induces mitotic arrest; its abundance is controlled by FBXL18, which ubiquitinates FBXL7 (at Lys109, via an FQ recognition motif) for proteasomal degradation, thereby limiting FBXL7-driven apoptosis.

PMID:25778398

The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial Function by Mediating the Ubiquitylation and Proteasomal Degradation of Survivin.

FBXL7, a component of the SCF (SKP1-CUL1-F-box) E3 ligase that regulates mitotic progression, mediates polyubiquitylation (at survivin Lys90/Lys91, via FBXL7 contact with survivin Glu126) and proteasomal degradation of survivin/BIRC5, regulating mitochondrial function.

PMID:28218735

Aurora kinase A regulates Survivin stability through targeting FBXL7 in gastric cancer drug resistance and prognosis.

In gastric cancer, AURKA upregulates the anti-apoptotic protein survivin; FBXL7 interacts with and polyubiquitinates survivin/BIRC5 for proteasomal degradation, linking the AURKA-FBXL7-survivin axis to drug resistance and prognosis.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:33234069

The FBXL family of F-box proteins: variations on a theme.

Review of the FBXL family describing FBXL7 as an SCF substrate receptor mediating SCF-dependent proteasomal degradation of its targets.

Reactome:R-HSA-8853496

SCF:FBXL7 binds AURKA

Reactome:R-HSA-8854041

SCF-FBXL7 ubiquitinates AURKA

Reactome:R-HSA-8854044

Proteasome degrades AURKA ubiquitinated by SCF-FBXL7

Reactome:R-HSA-8854051

SCF-FBXL18 ubiquitinates FBXL7

Reactome:R-HSA-8854052

Formation of the SCF-FBXL7 complex

Reactome:R-HSA-8854071

Proteasome-mediated degradation of PolyUb-FBXL7

Reactome:R-HSA-8952618

AcM-UBE2M transfers NEDD8 to CRL1 E3 ubiquitin ligase complex

Reactome:R-HSA-8952620

NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex

Reactome:R-HSA-8955241

CAND1 binds cytosolic CRL E3 ubiquitin ligases

Reactome:R-HSA-8955289

COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes

Reactome:R-HSA-8956040

COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes

Reactome:R-HSA-8956200

MyrG-DCUN1D3 binds CRL1 E3 ubiquitin ligase complex

Reactome:R-HSA-983140

Transfer of Ub from E2 to substrate and release of E2

Reactome:R-HSA-983147

Release of E3 from polyubiquitinated substrate

Reactome:R-HSA-983156

Polyubiquitination of substrate

Reactome:R-HSA-983157

Interaction of E3 with substrate and E2-Ub complex

file:human/FBXL7/FBXL7-deep-research-falcon.md

Falcon deep research report for human FBXL7

FBXL7 is a 491-residue FBXL-family protein with an N-terminal F-box motif (for SKP1/SCF assembly) and roughly eleven C-terminal leucine-rich repeats (the substrate-binding interface); it is the substrate-recognition subunit of an SCF (SKP1-CUL1-RBX1-F-box) E3 ligase.

"A 2022 expert review explicitly describes **human FBXL7** as a **491-aa** protein on chromosome **5p15.1** containing an **N-terminal F-box motif** (for SCF complex binding) and **~11 C-terminal leucine-rich repeats (LRRs)** (substrate binding), matching the UniProt domain expectations (F-box + LRRs) and the FBXL family classification."
FBXL7 colocalizes with Aurora A and targets it for centrosomal polyubiquitylation and degradation during mitosis, linking FBXL7 to spindle defects, polyploidy, and G2/M / mitotic arrest.

"Multiple authoritative sources cite **Aurora A kinase (AURKA)** as an early/central FBXL7 substrate, with FBXL7 promoting AURKA polyubiquitylation and degradation during mitosis and associating this with mitotic spindle/cell-cycle phenotypes."
SCF-FBXL7 targets the anti-apoptotic protein survivin/BIRC5 for proteasomal degradation (recognition via survivin E126, ubiquitin acceptor sites K90/K91), making FBXL7 proapoptotic and regulating mitochondrial function.

"Mapping of FBXL7–survivin interaction determinants and ubiquitylation acceptor sites: **E126** is important for recognition, and **K90/K91** serve as ubiquitin acceptors (mutants resist FBXL7-mediated effects)."
FBXL7 acts as a metastasis suppressor by ubiquitinating and degrading additional substrates - active c-SRC (after Ser104 phosphorylation) and the EMT transcription factor SNAI1/Snail1 - and is itself silenced in cancer by promoter hypermethylation and by hypoxia-induced EZH2 (which stabilizes the FBXL7 substrate PFKFB4 to drive glycolysis).

"A high-impact cancer epigenetics study established FBXL7 as a **metastasis-suppressor axis component** through control of **active c-SRC**: FBXL7 mediates **ubiquitylation and proteasomal degradation of active c-SRC after phosphorylation at Ser104**, and loss of FBXL7 promotes EMT and metastasis."

Suggested Experiments

Experiment: Reconstitute SCF(FBXL7)-mediated ubiquitination of AURKA and of survivin/BIRC5 in vitro with purified SKP1, CUL1, RBX1, an E2, and wild-type versus substrate-binding-mutant FBXL7 to map substrate lysine sites and confirm direct, SCF-dependent polyubiquitination.

Experiment: Perform synchronized cell-cycle proteomics and live-cell imaging in FBXL7-knockout versus wild-type cells to quantify AURKA and survivin turnover across mitosis, define FBXL7's centrosomal localization dynamics, and test the apoptotic consequences of substrate stabilization.

Deep Research

Falcon

(FBXL7-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 34 citations 2 artifacts 2026-06-13T06:11:35.011366

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000013 Figure 2d summarizes key data showing the correlation between FBXL7 promoter methylation and prostate cancer progression. The three (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: Human FBXL7 (UniProt Q9UJT9) — functional annotation, pathways, and translational relevance

0) Target verification (critical identity check)

The literature retrieved and analyzed is consistent with the UniProt entry Q9UJT9 for Homo sapiens FBXL7 (F-box/LRR-repeat protein 7). A 2022 expert review explicitly describes human FBXL7 as a 491-aa protein on chromosome 5p15.1 containing an N-terminal F-box motif (for SCF complex binding) and ~11 C-terminal leucine-rich repeats (LRRs) (substrate binding), matching the UniProt domain expectations (F-box + LRRs) and the FBXL family classification. (wang2022functionalcharacterizationof pages 2-3, wang2022functionalcharacterizationof pages 1-2)

1) Key concepts and definitions (current understanding)

1.1 The SCF E3 ubiquitin ligase and F-box proteins

FBXL7 functions as a substrate-recognition subunit of an SCF-type cullin-RING E3 ubiquitin ligase (SKP1–CUL1–RBX1–F-box). In this architecture, the F-box mediates assembly with SKP1, while LRRs provide the primary substrate-binding interface, enabling polyubiquitylation of selected proteins and subsequent proteasomal degradation. This general role of FBXL7 as an SCF substrate adaptor is reiterated across mechanistic and review sources. (wang2022functionalcharacterizationof pages 2-3, wang2022functionalcharacterizationof pages 1-2)

1.2 FBXL7 as a “substrate adaptor” (not an enzyme with a classical catalytic reaction)

FBXL7 is not itself an E2/E3 catalytic domain enzyme; rather, it confers substrate specificity to the SCF E3 ligase. Its “primary function” is therefore best described as directing ubiquitin-dependent degradation of specific protein substrates that regulate mitosis, survival/apoptosis, EMT/metastasis, and metabolic reprogramming. (wang2022functionalcharacterizationof pages 2-3, wang2022functionalcharacterizationof pages 1-2)

2) Molecular function and validated substrates (mechanistic evidence)

2.1 BIRC5/Survivin — apoptosis and mitochondrial homeostasis

A foundational mechanistic study demonstrated that SCF–FBXL7 targets the anti-apoptotic protein survivin (BIRC5) for polyubiquitylation and proteasomal degradation, linking FBXL7 to pro-apoptotic activity and mitochondrial functional regulation. Key mechanistic details include:
- Survivin half-life ~2 hours and stabilization by proteasome inhibition (MG132), supporting proteasome-dependent turnover. (liu2015theproapoptoticfbox pages 4-5)
- Mapping of FBXL7–survivin interaction determinants and ubiquitylation acceptor sites: E126 is important for recognition, and K90/K91 serve as ubiquitin acceptors (mutants resist FBXL7-mediated effects). (liu2015theproapoptoticfbox pages 6-8, liu2015theproapoptoticfbox pages 1-2)
- Quantitative phenotype: FBXL7 overexpression reduced Mfn1 by ~36% and decreased ATP in a dose-dependent manner, consistent with mitochondrial impairment when survivin is depleted. (liu2015theproapoptoticfbox pages 4-5)

2.2 SRC (c-SRC) — EMT and metastasis suppression via degradation of active SRC

A high-impact cancer epigenetics study established FBXL7 as a metastasis-suppressor axis component through control of active c-SRC: FBXL7 mediates ubiquitylation and proteasomal degradation of active c-SRC after phosphorylation at Ser104, and loss of FBXL7 promotes EMT and metastasis. (moro2020epigeneticsilencingof pages 1-2)

A key translational feature is that the FBXL7 promoter can be epigenetically silenced (hypermethylation), and the authors showed that the DNA-demethylating drug decitabine can restore FBXL7 and reduce EMT/invasion in a c-SRC-dependent manner. (moro2020epigeneticsilencingof pages 1-2)

Figure-based clinical association: A panel from this study shows that FBXL7 promoter methylation correlates positively with prostate cancer severity metrics (Gleason grade, pT stage, overall stage), supporting clinical relevance of epigenetic silencing during progression. (moro2020epigeneticsilencingof media 119c2419)

2.3 SNAI1 (Snail1) — EMT control in pancreatic cancer

In pancreatic cancer models, FBXL7 physically interacts with Snail1 and promotes its polyubiquitylation and proteasomal degradation, thereby suppressing EMT phenotypes and metastasis. (tang2021downregulatedfboxlrrrepeatprotein pages 6-8)

This work includes in vivo metastasis evidence: FBXL7 knockdown increased metastatic burden in liver and lung in tail-vein injection assays (n=10 per cohort reported for metastasis counts) and increased Snail1 staining in tumors, consistent with an FBXL7→Snail1 degradation mechanism controlling metastatic potential. (tang2021downregulatedfboxlrrrepeatprotein pages 8-10)

2.4 PFKFB4 — glycolysis and hypoxia-driven metabolic reprogramming in NSCLC (2023)

A 2023 Cell Death & Disease study identified PFKFB4 as a substrate of FBXL7 in NSCLC using tandem affinity purification / mass spectrometry and mechanistic validation. FBXL7 ubiquitinates and degrades PFKFB4, suppressing glucose metabolism and malignant phenotypes; in contrast, hypoxia stabilizes PFKFB4 by repressing FBXL7. (zhou2023hypoxiamediatedpromotionof pages 1-2, zhou2023hypoxiamediatedpromotionof pages 6-7)

Mechanistic chain (hypoxia axis): Hypoxia → HIF-1α up → EZH2 up → FBXL7 transcription repressed → PFKFB4 stabilized → glycolysis and malignant phenotypes increased, with EZH2 knockdown reducing tumor growth through this axis. (zhou2023hypoxiamediatedpromotionof pages 1-2)

Quantitative statistic: Within the same study’s clinical association for the downstream enzyme PFKFB4, higher PFKFB4 expression is associated with worse survival in lung cancer datasets (reported HR 1.38, 95% CI 1.17–1.63; log-rank P=0.00012). (zhou2023hypoxiamediatedpromotionof pages 4-5)

2.5 AURKA (Aurora A) — mitosis and centrosomal degradation

Multiple authoritative sources cite Aurora A kinase (AURKA) as an early/central FBXL7 substrate, with FBXL7 promoting AURKA polyubiquitylation and degradation during mitosis and associating this with mitotic spindle/cell-cycle phenotypes. (wang2022functionalcharacterizationof pages 2-3, wang2022functionalcharacterizationof pages 1-2)

3) Subcellular localization (what can be stated from the evidence)

The most explicit localization evidence in the retrieved corpus is that FBXL7 colocalizes with Aurora A and mediates centrosomal degradation during mitosis, consistent with a mitotic/cell-cycle compartment for at least one substrate pathway. (wang2022functionalcharacterizationof pages 2-3)

Other substrate contexts imply localization at:
- Mitochondrial function control via survivin-dependent mitochondrial phenotypes, although the study emphasizes functional mitochondrial outcomes rather than definitive FBXL7 mitochondrial residency. (liu2015theproapoptoticfbox pages 6-8, liu2015theproapoptoticfbox pages 4-5)
- SRC/EMT signaling via degradation of active SRC and EMT-related transcriptional programs, which generally operate at membrane-associated signaling complexes and downstream transcriptional effectors; the mechanistic paper provides direct evidence of SRC degradation and EMT suppression rather than a strict FBXL7 compartment map. (moro2020epigeneticsilencingof pages 1-2)

4) Pathways and biological processes (integrated view)

Across mechanistic and review evidence, FBXL7 influences multiple pathways by controlling abundance of key regulatory proteins:

Ubiquitin–proteasome system (UPS) / SCF E3 ligase function (core molecular role) (wang2022functionalcharacterizationof pages 2-3, wang2022functionalcharacterizationof pages 1-2)
Mitosis / cell-cycle progression through AURKA degradation at centrosomes (wang2022functionalcharacterizationof pages 2-3)
Apoptosis and mitochondrial bioenergetics via survivin degradation, with measurable mitochondrial damage and ATP changes (liu2015theproapoptoticfbox pages 4-5)
EMT and metastasis via degradation of Snail1 and active SRC (tang2021downregulatedfboxlrrrepeatprotein pages 6-8, moro2020epigeneticsilencingof pages 1-2)
Hypoxia-linked glycolysis/metabolic rewiring via EZH2 repression of FBXL7 and stabilization of PFKFB4 (zhou2023hypoxiamediatedpromotionof pages 1-2)

5) Recent developments (prioritizing 2023–2024)

5.1 2023: EZH2/FBXL7/PFKFB4 axis connects epigenetic regulation to tumor glycolysis (NSCLC)

The 2023 NSCLC study advances FBXL7 functional annotation by adding a metabolic enzyme substrate (PFKFB4) and a hypoxia-driven epigenetic repression mechanism via EZH2. (zhou2023hypoxiamediatedpromotionof pages 1-2)

5.2 2024: Small-molecule natural product (dioscin) leverages FBXL7–survivin degradation (NSCLC)

A 2024 study reports that dioscin promotes proteasome-dependent survivin degradation by strengthening FBXL7–survivin interaction and increasing survivin ubiquitination; FBXL7 knockdown attenuates survivin loss, caspase-3 activation, and cytotoxicity. Quantitatively, 5 µM dioscin for 72 h reduced NSCLC cell viability by >90%, and xenograft experiments used 10 mg/kg i.p. every 2 days (n=6). (wang2024dioscininhibitsnonsmall pages 4-5)

This supports a “functional drug mechanism” in which FBXL7 acts as an E3 adaptor that can be pharmacologically engaged indirectly to deplete survivin. (wang2024dioscininhibitsnonsmall pages 4-5)

5.3 2024: Radioresistance signaling converges on survivin phosphorylation and FBXL7-mediated degradation (NPC)

A 2024 nasopharyngeal carcinoma (NPC) study identifies that TRAF4 promotes radioresistance, and that TRAF4 knockdown increases radiosensitivity possibly via inhibition of Akt/Wee1/CDK1 signaling, suppressing survivin phosphorylation and promoting survivin degradation by FBXL7. The study includes patient tissue work (NPC tumors and matched adjacent tissues, n=67) and notes correlation of TRAF4 with p-Akt and survivin in tissues. (liao2024traf4regulatesubiquitinationmodulated pages 1-2)

5.4 2024: Liquid biopsy implementation — cfDNA 5hmC classifier includes FBXL7 (gastric cancer)

A 2024 Gastric Cancer paper developed a cfDNA 5-hydroxymethylcytosine (5hmC)-based diagnostic model for gastric cancer and reports strong ROC performance by stage in a GEO testing set (AUC 0.89 for stage I vs controls; AUC 0.97 for stage II vs controls; AUC 0.89 for stage III–IV vs controls). The discussion explicitly includes FBXL7 among mechanistically relevant genes, citing its reported interaction with survivin and SCF E3 ligase role. (fu2024genomewide5hydroxymethylcytosinesin pages 9-10, fu2024genomewide5hydroxymethylcytosinesin pages 10-11)

6) Current applications and real-world implementations

Epigenetic therapy strategy (preclinical/translational): FBXL7 promoter hypermethylation can silence its metastasis-suppressor function; decitabine restores FBXL7 and reduces EMT/invasion and metastasis in an FBXL7-dependent manner in preclinical models. This is a concrete “implementation” of FBXL7 biology in a therapeutic concept (epigenetic reactivation to restore substrate degradation such as SRC). (moro2020epigeneticsilencingof pages 1-2)
Biomarker applications in oncology:
Ovarian cancer chemotherapy response/prognosis: FBXL7 upregulation is implicated as a predictor of poor outcomes and is associated with paclitaxel resistance in ovarian cancer, including correlations between FBXL7 mRNA and paclitaxel IC50 across cell lines and survival associations in patients (qualitative in extracted pages). (chiu2018fbxl7upregulationpredicts pages 10-12)
UADT tumor methylation biomarker: FBXL7 gene-body hypomethylation is described as having high discriminatory potential between tumor and non-tumor tissues in UADT cancers, suggesting a biomarker role (quantitative AUC not present in extracted pages). (camuzi2022fbxl7bodyhypomethylation pages 1-2)
cfDNA 5hmC liquid biopsy for gastric cancer: stage-stratified AUC values suggest near-term translational utility as a noninvasive marker set that includes FBXL7 gene-body 5hmC. (fu2024genomewide5hydroxymethylcytosinesin pages 9-10)
Pharmacologic sensitization concepts (preclinical):
Dioscin induces survivin loss via FBXL7-dependent ubiquitination, supporting FBXL7-pathway engagement for cytotoxicity in NSCLC. (wang2024dioscininhibitsnonsmall pages 4-5)
Radiosensitization via TRAF4/Akt/Wee1/CDK1 modulation leading to FBXL7-mediated survivin degradation. (liao2024traf4regulatesubiquitinationmodulated pages 1-2)
Clinical trials: Searches did not yield FBXL7-targeted interventional trials in the retrieved trial set, suggesting FBXL7 translation is currently focused on pathway/biomarker integration rather than direct FBXL7-targeted therapeutics. (OpenTargets Search: -FBXL7)

7) Expert opinions and authoritative synthesis

A 2022 review consolidates the concept that FBXL7 can behave as either a tumor suppressor or context-dependent oncogenic factor depending on tissue and dominant substrate network, summarizing upstream regulators and diverse downstream substrates spanning mitosis (AURKA), apoptosis (survivin), EMT/metastasis (SRC/Snail1), and metabolic rewiring. (wang2022functionalcharacterizationof pages 2-3)
Broader cancer-oriented F-box protein reviews also position FBXL7 among F-box proteins with clinically relevant substrate networks and potential biomarker/therapeutic value, including the Aurora A and survivin axes. (tekcham2020fboxproteinsand pages 4-6)

8) Key statistics and data highlights (from retrieved evidence)

Survivin half-life ~2 h; stabilized by MG132, not by lysosome inhibition (leupeptin). (liu2015theproapoptoticfbox pages 4-5)
Mfn1 reduced by ~36% upon FBXL7 overexpression in one model; ATP decreases dose-dependently. (liu2015theproapoptoticfbox pages 4-5)
PFKFB4 survival association in lung cancer datasets: HR 1.38 (95% CI 1.17–1.63), log-rank P=0.00012 (downstream of FBXL7 in NSCLC hypoxia axis). (zhou2023hypoxiamediatedpromotionof pages 4-5)
Dioscin cytotoxicity and dosing (NSCLC): 5 µM for 72 h reduced viability by >90%; xenograft dosing 10 mg/kg i.p. every 2 days, n=6. (wang2024dioscininhibitsnonsmall pages 4-5)
cfDNA 5hmC diagnostic performance (gastric cancer, stage-stratified): AUC 0.89 (stage I), 0.97 (stage II), 0.89 (stage III–IV) vs controls in the GEO testing set. (fu2024genomewide5hydroxymethylcytosinesin pages 9-10)
NPC tissue cohort size: n=67 tumor and matched adjacent non-tumor tissues. (liao2024traf4regulatesubiquitinationmodulated pages 1-2)

9) Evidence map (compact summary table)

The following table consolidates domains, substrates, upstream regulators, phenotypes, and quantitative highlights.

Category	Finding	System/cancer type	Evidence type	Citation IDs	URL and year
Identity / complex	Human FBXL7 (UniProt Q9UJT9) is a 491-aa FBXL-family F-box protein that serves as the substrate-recognition subunit of SCF (SKP1–CUL1–RBX1–F-box) E3 ubiquitin ligases	Human	Review synthesizing primary studies	(wang2022functionalcharacterizationof pages 2-3, wang2022functionalcharacterizationof pages 1-2)	https://doi.org/10.1038/s41420-022-01143-w (2022)
Domains	FBXL7 contains an N-terminal F-box motif for SKP1 binding and ~11 C-terminal leucine-rich repeats (LRRs); review also notes an N-terminal serine-rich region	Human	Review / structural-functional annotation	(wang2022functionalcharacterizationof pages 2-3, wang2022functionalcharacterizationof pages 1-2)	https://doi.org/10.1038/s41420-022-01143-w (2022)
Validated substrate	AURKA/Aurora A is a canonical FBXL7 substrate; FBXL7 promotes AURKA polyubiquitylation and turnover, causing centrosomal degradation during mitosis	Cell cycle / mitotic models; cancer context	Primary biochemical/cell biology summarized in review	(wang2022functionalcharacterizationof pages 2-3, wang2022functionalcharacterizationof pages 1-2)	https://doi.org/10.1038/s41420-022-01143-w (2022)
Phenotypic output	AURKA degradation by FBXL7 is linked to spindle defects, polyploidy, G2/M arrest, and mitotic arrest	Mitotic models	Primary functional studies summarized in review	(wang2022functionalcharacterizationof pages 2-3, wang2022functionalcharacterizationof pages 1-2)	https://doi.org/10.1038/s41420-022-01143-w (2022)
Localization / pathway note	FBXL7 colocalizes with Aurora A and targets it for centrosomal degradation during mitosis	Mitotic models	Primary cell biology summarized in review	(wang2022functionalcharacterizationof pages 2-3)	https://doi.org/10.1038/s41420-022-01143-w (2022)
Validated substrate	BIRC5/survivin is directly recognized by SCF-FBXL7 and degraded by the proteasome	Lung epithelial cells / broad cell biology	Primary biochemical study	(liu2015theproapoptoticfbox pages 6-8, liu2015theproapoptoticfbox pages 4-5, liu2015theproapoptoticfbox pages 1-2)	https://doi.org/10.1074/jbc.m114.629931 (2015)
Quantitative finding	Endogenous survivin half-life is ~2 h; MG132 stabilizes survivin decay whereas leupeptin does not	Cell culture	Primary kinetics / inhibitor evidence	(liu2015theproapoptoticfbox pages 4-5)	https://doi.org/10.1074/jbc.m114.629931 (2015)
Mechanistic detail	Survivin recognition involves residue E126, and Lys90/Lys91 serve as ubiquitin acceptor sites; E126A and K90R/K91R mutants resist FBXL7 effects	Cell culture / biochemical assays	Primary mutational analysis	(liu2015theproapoptoticfbox pages 6-8, liu2015theproapoptoticfbox pages 1-2)	https://doi.org/10.1074/jbc.m114.629931 (2015)
Phenotypic output	FBXL7 overexpression impairs mitochondrial function and promotes apoptosis; survivin counters FBXL7-induced mitochondrial defects	Lung epithelial cells	Primary functional study	(liu2015theproapoptoticfbox pages 6-8, liu2015theproapoptoticfbox pages 1-2)	https://doi.org/10.1074/jbc.m114.629931 (2015)
Quantitative finding	Overexpression of wild-type FBXL7 reduced Mfn1 protein by 36% and lowered ATP in a dose-dependent manner	MLE cells	Primary quantitative cell biology	(liu2015theproapoptoticfbox pages 4-5)	https://doi.org/10.1074/jbc.m114.629931 (2015)
Validated substrate	Active c-SRC is targeted by FBXL7 after phosphorylation at Ser104, leading to ubiquitylation and proteasomal degradation	Prostate and pancreatic cancer	Primary mechanistic cancer study	(moro2020epigeneticsilencingof pages 1-2, wang2022functionalcharacterizationof pages 2-3)	https://doi.org/10.1038/s41556-020-0560-6 (2020)
Upstream regulation	FBXL7 promoter hypermethylation lowers FBXL7 mRNA/protein in advanced prostate and pancreatic cancers	Prostate and pancreatic cancer	Primary epigenetic/clinical association	(moro2020epigeneticsilencingof pages 1-2, moro2020epigeneticsilencingof media 119c2419)	https://doi.org/10.1038/s41556-020-0560-6 (2020)
Therapeutic modulation	Decitabine restores FBXL7 expression and limits EMT/invasion in a c-SRC-dependent manner; dasatinib suppresses metastasis when FBXL7 is depleted	Prostate and pancreatic cancer	Primary intervention study	(moro2020epigeneticsilencingof pages 1-2)	https://doi.org/10.1038/s41556-020-0560-6 (2020)
Phenotypic output	FBXL7 acts as a metastasis suppressor by restraining c-SRC-driven EMT and invasion; depletion increases metastatic burden in vivo	Prostate and pancreatic cancer	Primary in vivo functional study	(moro2020epigeneticsilencingof pages 1-2)	https://doi.org/10.1038/s41556-020-0560-6 (2020)
Validated substrate	SNAI1/Snail1 binds FBXL7 and undergoes ubiquitination/proteasomal degradation	Pancreatic cancer	Primary cancer study	(wang2022functionalcharacterizationof pages 2-3)	https://doi.org/10.1038/s41420-022-01143-w (2022)
Phenotypic output	Through Snail1 degradation, FBXL7 suppresses EMT, invasion, and metastasis	Pancreatic cancer	Primary cancer study summarized in review	(wang2022functionalcharacterizationof pages 2-3)	https://doi.org/10.1038/s41420-022-01143-w (2022)
Validated substrate	PFKFB4 was identified as an FBXL7 substrate; FBXL7 ubiquitinates and degrades PFKFB4	NSCLC	Primary 2023 study	(zhou2023hypoxiamediatedpromotionof pages 6-7, zhou2023hypoxiamediatedpromotionof pages 1-2)	https://doi.org/10.1038/s41419-023-05795-z (2023)
Upstream regulation	Hypoxia increases HIF-1α, which elevates EZH2; EZH2 represses FBXL7 transcription, stabilizing PFKFB4 and enhancing glycolysis	NSCLC under hypoxia	Primary mechanistic study	(zhou2023hypoxiamediatedpromotionof pages 6-7, zhou2023hypoxiamediatedpromotionof pages 1-2)	https://doi.org/10.1038/s41419-023-05795-z (2023)
Phenotypic output	FBXL7 re-expression suppresses viability, migration, invasion, glucose metabolism, and promotes apoptosis; effects are significant across repeated experiments	NSCLC (A549, H1650)	Primary functional study	(zhou2023hypoxiamediatedpromotionof pages 4-5, zhou2023hypoxiamediatedpromotionof pages 6-7)	https://doi.org/10.1038/s41419-023-05795-z (2023)
Quantitative finding	Higher PFKFB4 expression is associated with worse survival in lung cancer: HR 1.38, 95% CI 1.17–1.63, log-rank P=0.00012	LUAD/LUSC datasets	Clinical association within mechanistic paper	(zhou2023hypoxiamediatedpromotionof pages 4-5)	https://doi.org/10.1038/s41419-023-05795-z (2023)
Upstream regulation	AURKA negatively regulates FBXL7 at transcriptional and translational levels through a FOXP1–FBXL7 axis, thereby limiting survivin degradation	Gastric cancer	Primary mechanistic cancer study	(tekcham2020fboxproteinsand pages 4-6)	https://doi.org/10.7150/thno.42735 (2020)
Network effect	AURKA restricts FBXL7-mediated survivin ubiquitylation, contributing to drug resistance	Gastric cancer	Review summarizing primary study	(tekcham2020fboxproteinsand pages 4-6)	https://doi.org/10.7150/thno.42735 (2020)
Drug-response application	In ovarian cancer, high FBXL7 transcript is associated with poor prognosis and unfavorable paclitaxel response; FBXL7 expression correlates with paclitaxel IC50 across cell lines	Ovarian cancer	Primary translational study summarized in search results	(tekcham2020fboxproteinsand pages 4-6)	https://doi.org/10.3390/jcm7100330 (2018)
Drug-response mechanism	Dioscin promotes proteasome-dependent survivin degradation by strengthening FBXL7–survivin interaction; FBXL7 knockdown blunts dioscin cytotoxicity	NSCLC	Primary 2024 pharmacology study	(wang2024dioscininhibitsnonsmall pages 4-5)	https://doi.org/10.7150/jca.89831 (2024)
Quantitative finding	In NSCLC cells, 5 μM dioscin for 72 h reduced viability by >90%; xenograft dosing was 10 mg/kg i.p. every 2 days (n=6/cohort)	NSCLC xenograft and cell lines	Primary 2024 preclinical study	(wang2024dioscininhibitsnonsmall pages 4-5)	https://doi.org/10.7150/jca.89831 (2024)
Biomarker / epigenetics	FBXL7 gene body hypomethylation is frequent in upper aerodigestive tract tumors, correlates with gene expression, and has high discriminatory potential between tumor and non-tumor tissue	ESCC, OCSCC, LSCC, OPSCC	Primary biomarker study	(camuzi2022fbxl7bodyhypomethylation pages 1-2)	https://doi.org/10.3390/ijms23147801 (2022)
Figure-based clinicopathology	FBXL7 promoter methylation positively correlates with Gleason grade, pathological stage, and overall disease stage in prostate cancer	Prostate cancer	Figure-derived clinical association	(moro2020epigeneticsilencingof media 119c2419)	https://doi.org/10.1038/s41556-020-0560-6 (2020)
Expert synthesis	Reviews place FBXL7 at the intersection of apoptosis, mitosis/cell-cycle control, mitochondrial homeostasis, EMT/metastasis, glucose metabolism, and drug response	Human cancers	Expert review	(wang2022functionalcharacterizationof pages 2-3, wang2022functionalcharacterizationof pages 1-2)	https://doi.org/10.1038/s41420-022-01143-w (2022)
Evidence gap / implementation	No FBXL7-targeted clinical trials were retrieved; current real-world implementation is mainly as a candidate biomarker/therapeutic axis rather than a validated drug target	Clinical translation	Negative search finding / evidence synthesis	(OpenTargets Search: -FBXL7)	Open Targets search context (accessed via tool; latest indexed evidence includes 2023–2024 literature)

Table: This table summarizes the core functional annotation of human FBXL7 (UniProt Q9UJT9), including its SCF-complex role, validated substrates, upstream regulators, phenotypic consequences, and key quantitative findings from primary and review literature. It is useful as a compact evidence map for molecular function, pathway context, and translational relevance.

10) Limitations and evidence gaps

Localization detail is partial in the retrieved texts: centrosomal/mitotic colocalization is well-supported (AURKA axis), but comprehensive subcellular mapping (e.g., cytosol vs nucleus vs membrane-associated pools) is not fully defined in the extracted pages. (wang2022functionalcharacterizationof pages 2-3)
Several biomarker-oriented reports (e.g., UADT methylation discriminatory power; ovarian cancer survival hazard ratios) are described qualitatively in the extracted segments but lack numeric effect sizes in the pulled text, and would require additional full-text sections for exact AUC/HR estimates. (camuzi2022fbxl7bodyhypomethylation pages 1-2, chiu2018fbxl7upregulationpredicts pages 10-12)

11) URLs and publication dates (selected primary sources prioritized to 2023–2024)

Zhou J. et al. Cell Death & Disease (May 2023): EZH2/FBXL7/PFKFB4 axis in NSCLC. https://doi.org/10.1038/s41419-023-05795-z (zhou2023hypoxiamediatedpromotionof pages 1-2)
Wang R. et al. Journal of Cancer (Jan 2024): Dioscin promotes FBXL7-mediated survivin degradation in NSCLC. https://doi.org/10.7150/jca.89831 (wang2024dioscininhibitsnonsmall pages 4-5)
Liao J. et al. International Journal of Biological Sciences (Published Jan 1, 2024): TRAF4 regulates survivin turnover; FBXL7 implicated in survivin degradation and radioresistance. https://doi.org/10.7150/ijbs.87180 (liao2024traf4regulatesubiquitinationmodulated pages 1-2)
Fu Y. et al. Gastric Cancer (Apr 2024): cfDNA 5hmC diagnostic markers including FBXL7; stage ROC AUCs. https://doi.org/10.1007/s10120-024-01493-7 (fu2024genomewide5hydroxymethylcytosinesin pages 9-10)

12) Conclusion

Human FBXL7 (UniProt Q9UJT9) is best supported as an SCF E3 ligase substrate adaptor whose LRR domain selects substrates for ubiquitin-dependent proteasomal degradation. Experimentally validated substrates include survivin (BIRC5) (apoptosis/mitochondrial function), active c-SRC and Snail1 (EMT/metastasis), AURKA (mitosis/centrosome), and PFKFB4 (glycolysis/metabolic phenotypes in NSCLC). Recent (2023–2024) studies expand FBXL7 biology into hypoxia–EZH2–metabolic rewiring, drug-induced enhancement of FBXL7–survivin interaction, radioresistance signaling, and liquid biopsy epigenomic marker panels, positioning FBXL7 as a cross-cutting node in cancer cell-cycle, survival, metastasis, and metabolic programs with emerging translational relevance. (wang2022functionalcharacterizationof pages 2-3, moro2020epigeneticsilencingof pages 1-2, zhou2023hypoxiamediatedpromotionof pages 1-2, wang2024dioscininhibitsnonsmall pages 4-5, liao2024traf4regulatesubiquitinationmodulated pages 1-2, fu2024genomewide5hydroxymethylcytosinesin pages 9-10)

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(moro2020epigeneticsilencingof media 119c2419): Loredana Moro, Daniele Simoneschi, Emma Kurz, Arnaldo A. Arbini, Shaowen Jang, Nicoletta Guaragnella, Sergio Giannattasio, Wei Wang, Yu-An Chen, Geoffrey Pires, Andrew Dang, Elizabeth Hernandez, Payal Kapur, Ankita Mishra, Aristotelis Tsirigos, George Miller, Jer-Tsong Hsieh, and Michele Pagano. Epigenetic silencing of the ubiquitin ligase subunit fbxl7 impairs c-src degradation and promotes epithelial-to-mesenchymal transition and metastasis. Aug 2020. URL: https://doi.org/10.1038/s41556-020-0560-6, doi:10.1038/s41556-020-0560-6. This article has 54 citations and is from a highest quality peer-reviewed journal.
(tang2021downregulatedfboxlrrrepeatprotein pages 6-8): Liang Tang, Meng Ji, Xing Liang, Danlei Chen, Anan Liu, Guang Yang, Ligang Shi, Zhiping Fu, and Chenghao Shao. Downregulated f-box/lrr-repeat protein 7 facilitates pancreatic cancer metastasis by regulating snail1 for proteasomal degradation. Frontiers in Genetics, Jun 2021. URL: https://doi.org/10.3389/fgene.2021.650090, doi:10.3389/fgene.2021.650090. This article has 5 citations and is from a peer-reviewed journal.
(tang2021downregulatedfboxlrrrepeatprotein pages 8-10): Liang Tang, Meng Ji, Xing Liang, Danlei Chen, Anan Liu, Guang Yang, Ligang Shi, Zhiping Fu, and Chenghao Shao. Downregulated f-box/lrr-repeat protein 7 facilitates pancreatic cancer metastasis by regulating snail1 for proteasomal degradation. Frontiers in Genetics, Jun 2021. URL: https://doi.org/10.3389/fgene.2021.650090, doi:10.3389/fgene.2021.650090. This article has 5 citations and is from a peer-reviewed journal.
(zhou2023hypoxiamediatedpromotionof pages 1-2): Jing Zhou, Yang Lin, Xiuhua Kang, Zhicheng Liu, Juntao Zou, and Fei Xu. Hypoxia-mediated promotion of glucose metabolism in non-small cell lung cancer correlates with activation of the ezh2/fbxl7/pfkfb4 axis. May 2023. URL: https://doi.org/10.1038/s41419-023-05795-z, doi:10.1038/s41419-023-05795-z. This article has 22 citations and is from a peer-reviewed journal.
(zhou2023hypoxiamediatedpromotionof pages 6-7): Jing Zhou, Yang Lin, Xiuhua Kang, Zhicheng Liu, Juntao Zou, and Fei Xu. Hypoxia-mediated promotion of glucose metabolism in non-small cell lung cancer correlates with activation of the ezh2/fbxl7/pfkfb4 axis. May 2023. URL: https://doi.org/10.1038/s41419-023-05795-z, doi:10.1038/s41419-023-05795-z. This article has 22 citations and is from a peer-reviewed journal.
(zhou2023hypoxiamediatedpromotionof pages 4-5): Jing Zhou, Yang Lin, Xiuhua Kang, Zhicheng Liu, Juntao Zou, and Fei Xu. Hypoxia-mediated promotion of glucose metabolism in non-small cell lung cancer correlates with activation of the ezh2/fbxl7/pfkfb4 axis. May 2023. URL: https://doi.org/10.1038/s41419-023-05795-z, doi:10.1038/s41419-023-05795-z. This article has 22 citations and is from a peer-reviewed journal.
(wang2024dioscininhibitsnonsmall pages 4-5): Ruirui Wang, Xiaoying Li, Yujie Gan, Jinzhuang Liao, Shuangze Han, Wei Li, and Gaoyan Deng. Dioscin inhibits non-small cell lung cancer cells and activates apoptosis by downregulation of survivin. Journal of Cancer, 15:1366-1377, Jan 2024. URL: https://doi.org/10.7150/jca.89831, doi:10.7150/jca.89831. This article has 9 citations and is from a peer-reviewed journal.
(liao2024traf4regulatesubiquitinationmodulated pages 1-2): Jinzhuang Liao, Xiang Qing, Xiaoying Li, Yujie Gan, Ruirui Wang, Shuangze Han, Wei Li, and Wei Song. Traf4 regulates ubiquitination-modulated survivin turnover and confers radioresistance. International Journal of Biological Sciences, 20:182-199, Jan 2024. URL: https://doi.org/10.7150/ijbs.87180, doi:10.7150/ijbs.87180. This article has 20 citations and is from a peer-reviewed journal.
(fu2024genomewide5hydroxymethylcytosinesin pages 9-10): Yingli Fu, Jing Jiang, Yanhua Wu, Donghui Cao, Zhifang Jia, Yangyu Zhang, Dongming Li, Yingnan Cui, Yuzheng Zhang, and Xueyuan Cao. Genome-wide 5-hydroxymethylcytosines in circulating cell-free dna as noninvasive diagnostic markers for gastric cancer. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 27:735-746, Apr 2024. URL: https://doi.org/10.1007/s10120-024-01493-7, doi:10.1007/s10120-024-01493-7. This article has 12 citations.
(fu2024genomewide5hydroxymethylcytosinesin pages 10-11): Yingli Fu, Jing Jiang, Yanhua Wu, Donghui Cao, Zhifang Jia, Yangyu Zhang, Dongming Li, Yingnan Cui, Yuzheng Zhang, and Xueyuan Cao. Genome-wide 5-hydroxymethylcytosines in circulating cell-free dna as noninvasive diagnostic markers for gastric cancer. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 27:735-746, Apr 2024. URL: https://doi.org/10.1007/s10120-024-01493-7, doi:10.1007/s10120-024-01493-7. This article has 12 citations.
(chiu2018fbxl7upregulationpredicts pages 10-12): Hui-Wen Chiu, Jeng-Shou Chang, Hui-Yu Lin, Hsun-Hua Lee, Chia-Hao Kuei, Che-Hsuan Lin, Huei-Mei Huang, and Yuan-Feng Lin. Fbxl7 upregulation predicts a poor prognosis and associates with a possible mechanism for paclitaxel resistance in ovarian cancer. Journal of Clinical Medicine, 7:330, Oct 2018. URL: https://doi.org/10.3390/jcm7100330, doi:10.3390/jcm7100330. This article has 18 citations.
(camuzi2022fbxl7bodyhypomethylation pages 1-2): Diego Camuzi, Luisa Aguirre Buexm, Simone de Queiroz Chaves Lourenço, Rachele Grazziotin, Simone Guaraldi, Priscila Valverde, Davy Rapozo, Jill M. Brooks, Hisham Mehanna, Luis Felipe Ribeiro Pinto, and Sheila Coelho Soares-Lima. Fbxl7 body hypomethylation is frequent in tumors from the digestive and respiratory tracts and is associated with risk-factor exposure. International Journal of Molecular Sciences, 23:7801, Jul 2022. URL: https://doi.org/10.3390/ijms23147801, doi:10.3390/ijms23147801. This article has 4 citations.
(OpenTargets Search: -FBXL7): Open Targets Query (-FBXL7, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(tekcham2020fboxproteinsand pages 4-6): Dinesh Singh Tekcham, Di Chen, Yu Liu, Ting Ling, Yi Zhang, Huan Chen, Wen Wang, Wuxiyar Otkur, Huan Qi, Tian Xia, Xiaolong Liu, Hai-long Piao, and Hongxu Liu. F-box proteins and cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects. Theranostics, 10:4150-4167, Mar 2020. URL: https://doi.org/10.7150/thno.42735, doi:10.7150/thno.42735. This article has 111 citations and is from a domain leading peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Citations

liu2015theproapoptoticfbox pages 4-5
moro2020epigeneticsilencingof pages 1-2
tang2021downregulatedfboxlrrrepeatprotein pages 6-8
tang2021downregulatedfboxlrrrepeatprotein pages 8-10
zhou2023hypoxiamediatedpromotionof pages 1-2
zhou2023hypoxiamediatedpromotionof pages 4-5
wang2022functionalcharacterizationof pages 2-3
wang2024dioscininhibitsnonsmall pages 4-5
tekcham2020fboxproteinsand pages 4-6
wang2022functionalcharacterizationof pages 1-2
liu2015theproapoptoticfbox pages 6-8
liu2015theproapoptoticfbox pages 1-2
zhou2023hypoxiamediatedpromotionof pages 6-7
https://doi.org/10.1038/s41420-022-01143-w
https://doi.org/10.1074/jbc.m114.629931
https://doi.org/10.1038/s41556-020-0560-6
https://doi.org/10.1038/s41419-023-05795-z
https://doi.org/10.7150/thno.42735
https://doi.org/10.3390/jcm7100330
https://doi.org/10.7150/jca.89831
https://doi.org/10.3390/ijms23147801
https://doi.org/10.7150/ijbs.87180
https://doi.org/10.1007/s10120-024-01493-7
https://doi.org/10.1038/s41420-022-01143-w,
https://doi.org/10.1074/jbc.m114.629931,
https://doi.org/10.1038/s41556-020-0560-6,
https://doi.org/10.3389/fgene.2021.650090,
https://doi.org/10.1038/s41419-023-05795-z,
https://doi.org/10.7150/jca.89831,
https://doi.org/10.7150/ijbs.87180,
https://doi.org/10.1007/s10120-024-01493-7,
https://doi.org/10.3390/jcm7100330,
https://doi.org/10.3390/ijms23147801,
https://doi.org/10.7150/thno.42735,

📚 Additional Documentation

Pn Notes

(FBXL7-pn-notes.md)

FBXL7 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q9UJT9
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-13
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/FBXL7/FBXL7-ai-review.yaml
AIGR review HTML: missing - genes/human/FBXL7/FBXL7-ai-review.html
Gene notes: missing - genes/human/FBXL7/FBXL7-notes.md
GOA TSV: present - genes/human/FBXL7/FBXL7-goa.tsv
UniProt record: present - genes/human/FBXL7/FBXL7-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/FBXL7.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/FBXL7.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

genes/human/FBXL7/FBXL7-deep-research-falcon.md

AIGR Review Snapshot

Description: FBXL7 (F-box/LRR-repeat protein 7) is the substrate-recognition (F-box) subunit of an SCF (SKP1-CUL1-RBX1-F-box) cullin-RING E3 ubiquitin ligase that controls mitotic progression and apoptosis by directing the ubiquitination and proteasomal degradation of mitotic regulators. Within the SCF(FBXL7) complex, FBXL7 binds SKP1 via its F-box domain and uses its leucine-rich repeats to recruit substrates, so that CUL1-RBX1 drives their polyubiquitination. Its best-characterized substrates are the mitotic kinase Aurora A (AURKA), which FBXL7 colocalizes with and targets for centrosomal degradation during mitosis to promote mitotic arrest, and the inhibitor-of-apoptosis protein survivin/BIRC5 (recognized via survivin Glu126; ubiquitinated at Lys90/Lys91), whose FBXL7-mediated degradation regulates mitochondrial function and promotes apoptosis. FBXL7 (a 491-residue protein with an N-terminal F-box motif and roughly eleven C-terminal leucine-rich repeats) additionally targets active c-SRC (after Ser104 phosphorylation) and the EMT transcription factor SNAI1/Snail1 for degradation, acting as a metastasis suppressor that restrains SRC- and Snail1-driven epithelial-mesenchymal transition and invasion, and it ubiquitinates the glycolytic enzyme PFKFB4, coupling FBXL7 to metabolic reprogramming. FBXL7 localizes to the centrosome during spindle formation. FBXL7 is itself a proapoptotic factor whose cellular abundance is controlled by the related F-box protein FBXL18, which ubiquitinates FBXL7 (at Lys109) for proteasomal degradation, and its expression is repressed transcriptionally (e.g. by hypoxia-induced EZH2 and by promoter hypermethylation in cancer). Through these activities FBXL7 contributes to the G2/M transition, spindle dynamics, apoptotic signaling, EMT/metastasis suppression, and metabolic control, and is implicated in cancer progression and drug resistance.
Existing/core annotation action counts: ACCEPT: 16; KEEP_AS_NON_CORE: 25; NEW: 1

PN Consistency Summary

Consistency: Strong. Deep research, review, PN annotation, and node mapping all describe FBXL7 as the SCF(FBXL7) receptor degrading AURKA and survivin/BIRC5 (validated: PMID:25778398 IDA, 28218735 IMP; FBXL18→FBXL7 axis PMID:25654763). Falcon extra substrates (c-SRC, SNAI1, PFKFB4) marked UNVERIFIED and held as leads. No contradictions.
PN story / NEW pressure: PN asserts the generic adaptor MF. FBXL7 GOA has NO MF beyond protein binding (no catalytic transferase). The review adds GO:1990756 as action: NEW (IDA, PMID:25778398) — exactly the batch-correct call, and it matches the PN-projected term (GO:1990756, goa_status=new_to_goa). Validated substrates already drive G2/M transition, regulation of apoptotic process, SCF-dependent catabolism BPs. Conclusion: adaptor MF correctly ADDED as NEW; no over-reach.
Evidence alignment: PN cites only "15340381/rev"; review uses gene-specific primaries (25778398, 28218735, 25654763, 33234069) — no overlap with the PN placeholder, richer evidence in review. Benign divergence.
Verdict: CONSISTENT / ACCEPT mapping. Exemplary application of the NEW→GO:1990756 pattern. No edits required.

Full Consistency Review

UniProt: Q9UJT9 · batch: proteostasis-batch-2026-06-13 · review status: COMPLETE
PN placement: UPS|E3 ubiquitin and UBL ligases|Cul1 substrate receptor|F-box|LRR ; PN-node mapping: group-level mapped / ok_for_propagation_to_go / GO:1990756; class context_only / too_broad / GO:0061630.
Consistency: Strong. Deep research, review, PN annotation, and node mapping all describe FBXL7 as the SCF(FBXL7) receptor degrading AURKA and survivin/BIRC5 (validated: PMID:25778398 IDA, 28218735 IMP; FBXL18→FBXL7 axis PMID:25654763). Falcon extra substrates (c-SRC, SNAI1, PFKFB4) marked UNVERIFIED and held as leads. No contradictions.
PN story / NEW pressure: PN asserts the generic adaptor MF. FBXL7 GOA has NO MF beyond protein binding (no catalytic transferase). The review adds GO:1990756 as action: NEW (IDA, PMID:25778398) — exactly the batch-correct call, and it matches the PN-projected term (GO:1990756, goa_status=new_to_goa). Validated substrates already drive G2/M transition, regulation of apoptotic process, SCF-dependent catabolism BPs. Conclusion: adaptor MF correctly ADDED as NEW; no over-reach.
Mapping strategy: Gene does not change the node. Status/scope right; PN-projected GO:1990756 is identical to the review MF (not broader/narrower). Canonical, multiply-validated substrate receptor (AURKA, survivin) — no orphan flag. Note: FBXL7 review already encodes the MF directly, so the PN "new_to_goa" projection is consistent with the review having materialized it.
Evidence alignment: PN cites only "15340381/rev"; review uses gene-specific primaries (25778398, 28218735, 25654763, 33234069) — no overlap with the PN placeholder, richer evidence in review. Benign divergence.
Verdict: CONSISTENT / ACCEPT mapping. Exemplary application of the NEW→GO:1990756 pattern. No edits required.

PN Dossier Context

review_batch: proteostasis-batch-2026-06-13
review_yaml: genes/human/FBXL7/FBXL7-ai-review.yaml
PN workbook rows: 1

PN row 1: Ubiquitin Proteasome System | E3 ubiquitin and UBL ligases | Cul1 substrate receptor | F-box | LRR

UniProt: Q9UJT9
In branches: UPS
Signature domains: IPR001810
Auxiliary domains: IPR001611, IPR032675
PN references (titles):
- 15340381 / rev
PN-node mapping records (path + ancestors):
- [subtype] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul1 substrate receptor|F-box|LRR
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a narrower substrate-receptor, adaptor, domain, or family subdivision already covered by the curated parent adaptor/receptor mapping. No additional direct GO mapping is needed at this node.
- [type] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul1 substrate receptor|F-box
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a narrower substrate-receptor, adaptor, domain, or family subdivision already covered by the curated parent adaptor/receptor mapping. No additional direct GO mapping is needed at this node.
- [group] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul1 substrate receptor
  status=mapped scope=ok_for_propagation_to_go GO=[GO:1990756 ubiquitin-like ligase-substrate adaptor activity]
  rationale: This PN group captures substrate receptors/adaptors for cullin/UBL ligase systems. The shared GO molecular-function target is ubiquitin-like ligase-substrate adaptor activity.
- [class] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases
  status=context_only scope=too_broad_to_propagate GO=[GO:0061630 ubiquitin protein ligase activity]
  rationale: This class is a genuine E3-ligase context, but its descendants include catalytic ligases, cullin scaffolds, substrate receptors, adaptors, cofactors, regulators, and UBL modifier systems. A class-level propagation would over-annotate.
- [branch] Ubiquitin Proteasome System
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.

Projected GO annotations (1)

GO:1990756 ubiquitin-like ligase-substrate adaptor activity | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cul1 substrate receptor

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.

📄 View Raw YAML

id: Q9UJT9
gene_symbol: FBXL7
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  FBXL7 (F-box/LRR-repeat protein 7) is the substrate-recognition (F-box)
  subunit of an SCF (SKP1-CUL1-RBX1-F-box) cullin-RING E3 ubiquitin ligase that
  controls mitotic progression and apoptosis by directing the ubiquitination and
  proteasomal degradation of mitotic regulators. Within the SCF(FBXL7) complex,
  FBXL7 binds SKP1 via its F-box domain and uses its leucine-rich repeats to
  recruit substrates, so that CUL1-RBX1 drives their polyubiquitination. Its
  best-characterized substrates are the mitotic kinase Aurora A (AURKA), which
  FBXL7 colocalizes with and targets for centrosomal degradation during mitosis
  to promote mitotic arrest, and the inhibitor-of-apoptosis protein
  survivin/BIRC5 (recognized via survivin Glu126; ubiquitinated at Lys90/Lys91),
  whose FBXL7-mediated degradation regulates mitochondrial function and promotes
  apoptosis. FBXL7 (a 491-residue protein with an N-terminal F-box motif and
  roughly eleven C-terminal leucine-rich repeats) additionally targets active
  c-SRC (after Ser104 phosphorylation) and the EMT transcription factor
  SNAI1/Snail1 for degradation, acting as a metastasis suppressor that restrains
  SRC- and Snail1-driven epithelial-mesenchymal transition and invasion, and it
  ubiquitinates the glycolytic enzyme PFKFB4, coupling FBXL7 to metabolic
  reprogramming. FBXL7 localizes to the centrosome during spindle formation.
  FBXL7 is itself a proapoptotic factor whose cellular abundance is controlled by
  the related F-box protein FBXL18, which ubiquitinates FBXL7 (at Lys109) for
  proteasomal degradation, and its expression is repressed transcriptionally
  (e.g. by hypoxia-induced EZH2 and by promoter hypermethylation in cancer).
  Through these activities FBXL7 contributes to the G2/M transition, spindle
  dynamics, apoptotic signaling, EMT/metastasis suppression, and metabolic
  control, and is implicated in cancer progression and drug resistance.
alternative_products:
- name: '1'
  id: Q9UJT9-1
- name: '2'
  id: Q9UJT9-2
  sequence_note: VSP_054751
existing_annotations:
- term:
    id: GO:1990756
    label: ubiquitin-like ligase-substrate adaptor activity
  evidence_type: IDA
  original_reference_id: PMID:25778398
  qualifier: enables
  review:
    summary: Proposed core molecular function. As the F-box/LRR substrate-recognition subunit of SCF(FBXL7), FBXL7 selects substrates (AURKA, survivin/BIRC5) for SCF-dependent polyubiquitination. This more informative MF term is not in the GOA, which lacks any explicit MF annotation for FBXL7.
    action: NEW
    reason: Captures the precise molecular function of FBXL7 as an SCF substrate-recognition adaptor, more informative than the bare protein binding annotations and absent from the existing GOA.
    supported_by:
    - reference_id: PMID:25778398
      supporting_text: Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin by interacting with Glu-126 within its carboxyl-terminal α helix
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Combined automated electronic assignment of centrosome localization, where FBXL7 acts during spindle formation. Core localization for its mitotic role.
    action: ACCEPT
    reason: Core localization; FBXL7 localizes to the centrosome during spindle formation, consistent with its mitotic substrate-targeting role.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Binary interactome reference map interactions. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome; bare protein binding is uninformative per curation guidelines.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: 'Q9UJT9; Q92609: TBC1D5; NbExp=3; IntAct=EBI-914660, EBI-742381'
- term:
    id: GO:0000086
    label: G2/M transition of mitotic cell cycle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Ortholog-based electronic assignment of involvement in the G2/M transition, consistent with FBXL7-driven AURKA degradation and mitotic arrest.
    action: ACCEPT
    reason: Core biological process; FBXL7 regulates mitotic progression (mitotic arrest via AURKA degradation).
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA, causing mitotic arrest
- term:
    id: GO:0000209
    label: protein polyubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Combined automated electronic assignment of protein polyubiquitination, the specific modification FBXL7 directs onto its substrates.
    action: ACCEPT
    reason: Correct; FBXL7 mediates substrate polyubiquitination, supported by IDA/IMP evidence (survivin).
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: regulates mitochondrial function by mediating the ubiquitination and proteasomal degradation of the apoptosis inhibitor BIRC5
- term:
    id: GO:0000278
    label: mitotic cell cycle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Ortholog-based electronic assignment of involvement in the mitotic cell cycle, consistent with FBXL7's role in mitotic regulation.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic relative to the specific G2/M transition and SCF-dependent degradation annotations.
    supported_by:
    - reference_id: PMID:25778398
      supporting_text: Fbxl7, a component of the Skp1·Cul1·F-box protein type ubiquitin E3 ligase, regulates mitotic cell cycle progression
- term:
    id: GO:0016567
    label: protein ubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Combined automated electronic assignment of protein ubiquitination, a parent of the specific SCF-dependent polyubiquitination FBXL7 mediates.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the specific SCF-dependent catabolic / polyubiquitination annotations better capture the role.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: 'PATHWAY: Protein modification; protein ubiquitination.'
- term:
    id: GO:0019005
    label: SCF ubiquitin ligase complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: part_of
  review:
    summary: Combined automated electronic assignment of SCF complex membership, the core assembly context for FBXL7.
    action: ACCEPT
    reason: Core cellular component; redundant with IDA/ISS evidence.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL7) composed of CUL1, SKP1, RBX1 and FBXL7
- term:
    id: GO:0031146
    label: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Combined automated electronic assignment of SCF-dependent proteasomal degradation, the core biological process of SCF(FBXL7).
    action: ACCEPT
    reason: Core biological process; redundant with the experimental IDA/IMP evidence (survivin/AURKA degradation).
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: regulates mitochondrial function by mediating the ubiquitination and proteasomal degradation of the apoptosis inhibitor BIRC5
- term:
    id: GO:0031146
    label: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
  evidence_type: NAS
  original_reference_id: PMID:33234069
  qualifier: involved_in
  review:
    summary: Author-statement (FBXL family review) assignment of the core SCF-dependent proteasomal degradation process.
    action: ACCEPT
    reason: Core biological process; consistent with the experimental substrate-degradation evidence.
    supported_by:
    - reference_id: PMID:25778398
      supporting_text: Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin
- term:
    id: GO:0042981
    label: regulation of apoptotic process
  evidence_type: NAS
  original_reference_id: PMID:25654763
  qualifier: involved_in
  review:
    summary: Author-statement (ComplexPortal) assignment of regulation of apoptosis; FBXL7 is a proapoptotic factor and its degradation of survivin/BIRC5 promotes apoptosis.
    action: ACCEPT
    reason: Supported biological process; FBXL7 is proapoptotic and regulates apoptosis via degradation of the IAP survivin/BIRC5.
    supported_by:
    - reference_id: PMID:25654763
      supporting_text: Fbxl18 regulates apoptosis by mediating ubiquitin-dependent proteasomal degradation of the pro-apoptotic protein Fbxl7
- term:
    id: GO:0000209
    label: protein polyubiquitination
  evidence_type: IMP
  original_reference_id: PMID:28218735
  qualifier: involved_in
  review:
    summary: Mutant-phenotype evidence that FBXL7 mediates polyubiquitination of BIRC5/survivin. Core activity.
    action: ACCEPT
    reason: Directly supported substrate polyubiquitination (survivin/BIRC5); consistent with FBXL7's SCF substrate-receptor function.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: this interaction allows BIRC5 to be polyubiquitinated by the SCF(FBXL7) E3 ubiquitin-protein ligase complex
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28218735
  qualifier: enables
  review:
    summary: Interaction with BIRC5/survivin (a FBXL7 substrate). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the functionally important FBXL7-BIRC5 substrate interaction but bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Interacts with BIRC5; this interaction allows BIRC5 to be polyubiquitinated by the SCF(FBXL7)
- term:
    id: GO:0019005
    label: SCF ubiquitin ligase complex
  evidence_type: IDA
  original_reference_id: PMID:25778398
  qualifier: part_of
  review:
    summary: Direct evidence that FBXL7 is a component of the SCF (SKP1-CUL1-F-box) E3 ligase complex. Core cellular component.
    action: ACCEPT
    reason: Core cellular component; FBXL7 is the F-box substrate receptor of the SCF(FBXL7) complex.
    supported_by:
    - reference_id: PMID:25778398
      supporting_text: Fbxl7, a component of the Skp1·Cul1·F-box protein type ubiquitin E3 ligase, regulates mitotic cell cycle progression
- term:
    id: GO:0031146
    label: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:25778398
  qualifier: involved_in
  review:
    summary: Direct evidence that SCF(FBXL7) drives proteasomal degradation of survivin/BIRC5. Core biological process.
    action: ACCEPT
    reason: Core biological process directly demonstrated; FBXL7 targets survivin for SCF-dependent proteasomal degradation.
    supported_by:
    - reference_id: PMID:25778398
      supporting_text: Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin
- term:
    id: GO:0031146
    label: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
  evidence_type: IMP
  original_reference_id: PMID:28218735
  qualifier: involved_in
  review:
    summary: Mutant-phenotype evidence linking FBXL7 to SCF-dependent degradation of survivin in the AURKA/gastric-cancer study. Core biological process.
    action: ACCEPT
    reason: Core biological process; FBXL7 mediates proteasomal degradation of survivin/BIRC5.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: regulates mitochondrial function by mediating the ubiquitination and proteasomal degradation of the apoptosis inhibitor BIRC5
- term:
    id: GO:0000209
    label: protein polyubiquitination
  evidence_type: IDA
  original_reference_id: PMID:25778398
  qualifier: involved_in
  review:
    summary: Direct evidence that FBXL7 polyubiquitinates survivin (at Lys90/Lys91). Core activity.
    action: ACCEPT
    reason: Directly demonstrated substrate polyubiquitination of survivin/BIRC5.
    supported_by:
    - reference_id: PMID:25778398
      supporting_text: Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25778398
  qualifier: enables
  review:
    summary: Interaction with survivin (via Glu-126 in its C-terminal helix). Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the functionally important FBXL7-survivin substrate interaction but bare protein binding is uninformative.
    supported_by:
    - reference_id: PMID:25778398
      supporting_text: Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin by interacting with Glu-126 within its carboxyl-terminal α helix
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8854051
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization (SCF-FBXL18 ubiquitinates FBXL7). Consistent with the cytoplasmic site of action.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome during spindle formation.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8854071
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization (proteasome-mediated degradation of PolyUb-FBXL7). Consistent with the cytoplasmic site of action.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8853496
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization (SCF:FBXL7 binds AURKA). Consistent with the cytoplasmic site of action.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8854041
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization (SCF-FBXL7 ubiquitinates AURKA). Consistent with the cytoplasmic site of action.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8854044
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization (proteasome degrades AURKA ubiquitinated by SCF-FBXL7). Consistent with the cytoplasmic site of action.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8854052
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization (formation of the SCF-FBXL7 complex). Consistent with the cytoplasmic site of action.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL7) composed of CUL1, SKP1, RBX1 and FBXL7
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8952618
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization (neddylation of CRL1). Generic CRL-pathway localization.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic compartment but from generic CRL neddylation-pathway context; the functionally salient localization is the centrosome.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8952620
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization (NEDD8:UBE2M binds CRL1). Generic CRL-pathway localization.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic compartment but from generic CRL-pathway context; redundant.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8955241
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization (CAND1 binds cytosolic CRL). Generic CRL-pathway localization.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic compartment but from generic CRL-regulation pathway context; redundant.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8955289
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization (COMMDs displace CAND1). Generic CRL-pathway localization.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic compartment but from generic CRL-regulation pathway context; redundant.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8956040
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization (COP9 signalosome deneddylates CRL). Generic CRL-pathway localization.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic compartment but from generic CRL-regulation pathway context; redundant.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8956200
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization (DCUN1D3 binds CRL1). Generic CRL-pathway localization.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic compartment but from generic CRL-regulation pathway context; redundant.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-983140
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization (transfer of Ub from E2 to substrate). Generic ubiquitination-pathway localization.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic compartment but from generic ubiquitination-pathway context; redundant.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-983147
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization (release of E3 from polyubiquitinated substrate). Generic ubiquitination-pathway localization.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic compartment but from generic ubiquitination-pathway context; redundant.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-983156
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization (polyubiquitination of substrate). Generic ubiquitination-pathway localization.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic compartment but from generic ubiquitination-pathway context; redundant.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-983157
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization (interaction of E3 with substrate and E2-Ub). Generic ubiquitination-pathway localization.
    action: KEEP_AS_NON_CORE
    reason: Correct cytoplasmic compartment but from generic ubiquitination-pathway context; redundant.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
- term:
    id: GO:0000086
    label: G2/M transition of mitotic cell cycle
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity assignment of involvement in the G2/M transition, consistent with FBXL7-driven AURKA degradation.
    action: ACCEPT
    reason: Core biological process; FBXL7 regulates the mitotic G2/M transition.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA, causing mitotic arrest
- term:
    id: GO:0000278
    label: mitotic cell cycle
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity assignment of involvement in the mitotic cell cycle.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic relative to the specific G2/M transition annotation.
    supported_by:
    - reference_id: PMID:25778398
      supporting_text: Fbxl7, a component of the Skp1·Cul1·F-box protein type ubiquitin E3 ligase, regulates mitotic cell cycle progression
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Sequence-similarity assignment of centrosome localization, where FBXL7 acts during spindle formation. Core localization.
    action: ACCEPT
    reason: Core localization; FBXL7 localizes to the centrosome during spindle formation.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Localizes to the centrosome during spindle formation.
- term:
    id: GO:0016567
    label: protein ubiquitination
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity assignment of protein ubiquitination, a parent of the specific SCF-dependent polyubiquitination FBXL7 mediates.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the specific polyubiquitination/SCF-dependent catabolic annotations better capture the role.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: 'PATHWAY: Protein modification; protein ubiquitination.'
- term:
    id: GO:0019005
    label: SCF ubiquitin ligase complex
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: part_of
  review:
    summary: Sequence-similarity assignment of SCF complex membership, the core assembly context for FBXL7.
    action: ACCEPT
    reason: Core cellular component; redundant with IDA/IEA evidence.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL7) composed of CUL1, SKP1, RBX1 and FBXL7
- term:
    id: GO:0031146
    label: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity assignment of SCF-dependent proteasomal degradation, the core biological process of SCF(FBXL7).
    action: ACCEPT
    reason: Core biological process; redundant with the experimental IDA/IMP evidence.
    supported_by:
    - reference_id: PMID:25778398
      supporting_text: Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin
- term:
    id: GO:0000151
    label: ubiquitin ligase complex
  evidence_type: NAS
  original_reference_id: PMID:10531035
  qualifier: part_of
  review:
    summary: Author-statement assignment (original F-box family paper) of being part of a ubiquitin ligase complex. A generic parent of the specific SCF complex.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; subsumed by the specific SCF ubiquitin ligase complex annotation.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL7)
- term:
    id: GO:0006511
    label: ubiquitin-dependent protein catabolic process
  evidence_type: NAS
  original_reference_id: PMID:10531035
  qualifier: involved_in
  review:
    summary: Author-statement assignment of ubiquitin-dependent protein catabolism, a parent of the specific SCF-dependent proteasomal degradation FBXL7 mediates.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the specific GO:0031146 (SCF-dependent proteasomal catabolic process) better captures the role.
    supported_by:
    - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
      supporting_text: regulates mitochondrial function by mediating the ubiquitination and proteasomal degradation of the apoptosis inhibitor BIRC5
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10531035
  title: Identification of a family of human F-box proteins.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Original identification of FBXL7 as an F-box protein; source of the generic ubiquitin ligase complex and ubiquitin-dependent catabolic NAS annotations. Full text not in cache.
- id: PMID:25654763
  title: F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7.
  findings:
  - statement: FBXL7 is a proapoptotic SCF subunit that induces mitotic arrest; its abundance is controlled by FBXL18, which ubiquitinates FBXL7 (at Lys109, via an FQ recognition motif) for proteasomal degradation, thereby limiting FBXL7-driven apoptosis.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available; establishes FBXL7 as proapoptotic and mitotic-arrest-inducing, and that FBXL18 controls FBXL7 stability. Supports the regulation-of-apoptosis annotation.
- id: PMID:25778398
  title: The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial Function by Mediating the Ubiquitylation and Proteasomal Degradation of Survivin.
  findings:
  - statement: FBXL7, a component of the SCF (SKP1-CUL1-F-box) E3 ligase that regulates mitotic progression, mediates polyubiquitylation (at survivin Lys90/Lys91, via FBXL7 contact with survivin Glu126) and proteasomal degradation of survivin/BIRC5, regulating mitochondrial function.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes survivin/BIRC5 as a direct FBXL7 substrate and FBXL7 as an SCF component regulating mitosis and mitochondrial function. Abstract-only in cache; supports IDA SCF/polyubiquitination/catabolic annotations.
- id: PMID:28218735
  title: Aurora kinase A regulates Survivin stability through targeting FBXL7 in gastric cancer drug resistance and prognosis.
  findings:
  - statement: In gastric cancer, AURKA upregulates the anti-apoptotic protein survivin; FBXL7 interacts with and polyubiquitinates survivin/BIRC5 for proteasomal degradation, linking the AURKA-FBXL7-survivin axis to drug resistance and prognosis.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes FBXL7-BIRC5 interaction and FBXL7-mediated survivin polyubiquitination in a cancer context. Abstract-only in cache; supporting text for substrate annotations drawn from UniProt summary of this paper.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Binary interactome reference map; source of a bare protein binding annotation.
- id: PMID:33234069
  title: 'The FBXL family of F-box proteins: variations on a theme.'
  findings:
  - statement: Review of the FBXL family describing FBXL7 as an SCF substrate receptor mediating SCF-dependent proteasomal degradation of its targets.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full text available; family review supporting the SCF-dependent catabolic process annotation.
- id: Reactome:R-HSA-8853496
  title: SCF:FBXL7 binds AURKA
  findings: []
- id: Reactome:R-HSA-8854041
  title: SCF-FBXL7 ubiquitinates AURKA
  findings: []
- id: Reactome:R-HSA-8854044
  title: Proteasome degrades AURKA ubiquitinated by SCF-FBXL7
  findings: []
- id: Reactome:R-HSA-8854051
  title: SCF-FBXL18 ubiquitinates FBXL7
  findings: []
- id: Reactome:R-HSA-8854052
  title: Formation of the SCF-FBXL7 complex
  findings: []
- id: Reactome:R-HSA-8854071
  title: Proteasome-mediated degradation of PolyUb-FBXL7
  findings: []
- id: Reactome:R-HSA-8952618
  title: AcM-UBE2M transfers NEDD8 to CRL1 E3 ubiquitin ligase complex
  findings: []
- id: Reactome:R-HSA-8952620
  title: NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex
  findings: []
- id: Reactome:R-HSA-8955241
  title: CAND1 binds cytosolic CRL E3 ubiquitin ligases
  findings: []
- id: Reactome:R-HSA-8955289
  title: COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes
  findings: []
- id: Reactome:R-HSA-8956040
  title: COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes
  findings: []
- id: Reactome:R-HSA-8956200
  title: MyrG-DCUN1D3 binds CRL1 E3 ubiquitin ligase complex
  findings: []
- id: Reactome:R-HSA-983140
  title: Transfer of Ub from E2 to substrate and release of E2
  findings: []
- id: Reactome:R-HSA-983147
  title: Release of E3 from polyubiquitinated substrate
  findings: []
- id: Reactome:R-HSA-983156
  title: Polyubiquitination of substrate
  findings: []
- id: Reactome:R-HSA-983157
  title: Interaction of E3 with substrate and E2-Ub complex
  findings: []
- id: file:human/FBXL7/FBXL7-deep-research-falcon.md
  title: Falcon deep research report for human FBXL7
  findings:
  - statement: FBXL7 is a 491-residue FBXL-family protein with an N-terminal F-box motif (for SKP1/SCF assembly) and roughly eleven C-terminal leucine-rich repeats (the substrate-binding interface); it is the substrate-recognition subunit of an SCF (SKP1-CUL1-RBX1-F-box) E3 ligase.
    supporting_text: A 2022 expert review explicitly describes **human FBXL7** as a **491-aa** protein on chromosome **5p15.1** containing an **N-terminal F-box motif** (for SCF complex binding) and **~11 C-terminal leucine-rich repeats (LRRs)** (substrate binding), matching the UniProt domain expectations (F-box + LRRs) and the FBXL family classification.
  - statement: FBXL7 colocalizes with Aurora A and targets it for centrosomal polyubiquitylation and degradation during mitosis, linking FBXL7 to spindle defects, polyploidy, and G2/M / mitotic arrest.
    supporting_text: Multiple authoritative sources cite **Aurora A kinase (AURKA)** as an early/central FBXL7 substrate, with FBXL7 promoting AURKA polyubiquitylation and degradation during mitosis and associating this with mitotic spindle/cell-cycle phenotypes.
  - statement: SCF-FBXL7 targets the anti-apoptotic protein survivin/BIRC5 for proteasomal degradation (recognition via survivin E126, ubiquitin acceptor sites K90/K91), making FBXL7 proapoptotic and regulating mitochondrial function.
    supporting_text: 'Mapping of FBXL7–survivin interaction determinants and ubiquitylation acceptor sites: **E126** is important for recognition, and **K90/K91** serve as ubiquitin acceptors (mutants resist FBXL7-mediated effects).'
  - statement: FBXL7 acts as a metastasis suppressor by ubiquitinating and degrading additional substrates - active c-SRC (after Ser104 phosphorylation) and the EMT transcription factor SNAI1/Snail1 - and is itself silenced in cancer by promoter hypermethylation and by hypoxia-induced EZH2 (which stabilizes the FBXL7 substrate PFKFB4 to drive glycolysis).
    supporting_text: 'A high-impact cancer epigenetics study established FBXL7 as a **metastasis-suppressor axis component** through control of **active c-SRC**: FBXL7 mediates **ubiquitylation and proteasomal degradation of active c-SRC after phosphorylation at Ser104**, and loss of FBXL7 promotes EMT and metastasis.'
  reference_review:
    relevance: HIGH
    correctness: UNVERIFIED
    review_notes: Falcon (Edison Scientific) deep-research synthesis. The AURKA and survivin/BIRC5 substrate axes are corroborated by the experimental cache (PMID:25778398, PMID:28218735). The additional substrates (c-SRC Ser104, SNAI1/Snail1, PFKFB4) and the EZH2/hypoxia and promoter-methylation regulation are drawn from primary cancer studies cited by author-year/DOI (liu2015, moro2020, tang2021, zhou2023, wang2022) rather than PMIDs and are not independently PubMed-verified here, so marked UNVERIFIED; treated as leads used to enrich the gene narrative, not to add unsupported GO terms.
core_functions:
- description: Functions as the substrate-recognition (F-box) subunit of an SCF (SKP1-CUL1-RBX1-FBXL7) cullin-RING E3 ubiquitin ligase that recruits the mitotic kinase Aurora A (AURKA) during mitosis for polyubiquitination and proteasomal degradation, contributing to control of the G2/M transition and mitotic progression.
  molecular_function:
    id: GO:1990756
    label: ubiquitin-like ligase-substrate adaptor activity
  locations:
  - id: GO:0005813
    label: centrosome
  supported_by:
  - reference_id: file:human/FBXL7/FBXL7-uniprot.txt
    supporting_text: During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA, causing mitotic arrest
  directly_involved_in:
  - id: GO:0000086
    label: G2/M transition of mitotic cell cycle
  - id: GO:0031146
    label: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
- description: As the SCF(FBXL7) substrate receptor, binds the inhibitor-of-apoptosis protein survivin/BIRC5 and directs its polyubiquitination and proteasomal degradation, thereby regulating mitochondrial function and promoting apoptosis.
  molecular_function:
    id: GO:1990756
    label: ubiquitin-like ligase-substrate adaptor activity
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:25778398
    supporting_text: Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin
  directly_involved_in:
  - id: GO:0031146
    label: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
  - id: GO:0042981
    label: regulation of apoptotic process
- description: As the SCF(FBXL7) substrate receptor, recognizes and directs the polyubiquitination and proteasomal degradation of additional substrates that drive epithelial-mesenchymal transition and metabolic reprogramming - active c-SRC (after Ser104 phosphorylation), the EMT transcription factor SNAI1/Snail1, and the glycolytic enzyme PFKFB4 - acting in cancer as a metastasis suppressor whose loss (via promoter hypermethylation or hypoxia/EZH2-driven transcriptional repression) promotes invasion and glycolysis. (Substrates beyond AURKA/survivin are reported in primary cancer literature summarized by the Falcon deep-research report and are not yet in the curated GOA.)
  molecular_function:
    id: GO:1990756
    label: ubiquitin-like ligase-substrate adaptor activity
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:human/FBXL7/FBXL7-deep-research-falcon.md
    supporting_text: 'A high-impact cancer epigenetics study established FBXL7 as a **metastasis-suppressor axis component** through control of **active c-SRC**: FBXL7 mediates **ubiquitylation and proteasomal degradation of active c-SRC after phosphorylation at Ser104**, and loss of FBXL7 promotes EMT and metastasis.'
  directly_involved_in:
  - id: GO:0031146
    label: SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
proposed_new_terms: []
suggested_questions:
- question: Are the two best-described FBXL7 substrates (AURKA and survivin/BIRC5) targeted by the same FBXL7 pool and cell-cycle window, or do distinct localizations (centrosomal versus cytosolic) and timing govern each substrate?
- question: How does the FBXL18-FBXL7 regulatory axis controlling FBXL7 abundance influence the balance between mitotic progression and apoptosis, and is it dysregulated in cancers with AURKA/survivin overexpression?
- question: FBXL7 is reported to degrade a broad substrate set (AURKA, survivin/BIRC5, active c-SRC, SNAI1/Snail1, PFKFB4) and behaves as a tumor suppressor or context-dependent oncogenic factor across tissues; which of these substrate axes is dominant in a given cell type, and what determines whether FBXL7 loss is pro- or anti-tumorigenic?
suggested_experiments:
- description: Reconstitute SCF(FBXL7)-mediated ubiquitination of AURKA and of survivin/BIRC5 in vitro with purified SKP1, CUL1, RBX1, an E2, and wild-type versus substrate-binding-mutant FBXL7 to map substrate lysine sites and confirm direct, SCF-dependent polyubiquitination.
- description: Perform synchronized cell-cycle proteomics and live-cell imaging in FBXL7-knockout versus wild-type cells to quantify AURKA and survivin turnover across mitosis, define FBXL7's centrosomal localization dynamics, and test the apoptotic consequences of substrate stabilization.

FBXL7

Gene Description

Existing Annotations Review

Core Functions

As the SCF(FBXL7) substrate receptor, binds the inhibitor-of-apoptosis protein survivin/BIRC5 and directs its polyubiquitination and proteasomal degradation, thereby regulating mitochondrial function and promoting apoptosis.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research report: Human FBXL7 (UniProt Q9UJT9) — functional annotation, pathways, and translational relevance

0) Target verification (critical identity check)

1) Key concepts and definitions (current understanding)

1.1 The SCF E3 ubiquitin ligase and F-box proteins

1.2 FBXL7 as a “substrate adaptor” (not an enzyme with a classical catalytic reaction)

2) Molecular function and validated substrates (mechanistic evidence)

2.1 BIRC5/Survivin — apoptosis and mitochondrial homeostasis

2.2 SRC (c-SRC) — EMT and metastasis suppression via degradation of active SRC

2.3 SNAI1 (Snail1) — EMT control in pancreatic cancer

2.4 PFKFB4 — glycolysis and hypoxia-driven metabolic reprogramming in NSCLC (2023)

2.5 AURKA (Aurora A) — mitosis and centrosomal degradation

3) Subcellular localization (what can be stated from the evidence)

4) Pathways and biological processes (integrated view)

5) Recent developments (prioritizing 2023–2024)

5.1 2023: EZH2/FBXL7/PFKFB4 axis connects epigenetic regulation to tumor glycolysis (NSCLC)

5.2 2024: Small-molecule natural product (dioscin) leverages FBXL7–survivin degradation (NSCLC)

5.3 2024: Radioresistance signaling converges on survivin phosphorylation and FBXL7-mediated degradation (NPC)

5.4 2024: Liquid biopsy implementation — cfDNA 5hmC classifier includes FBXL7 (gastric cancer)

6) Current applications and real-world implementations

7) Expert opinions and authoritative synthesis

8) Key statistics and data highlights (from retrieved evidence)

9) Evidence map (compact summary table)

10) Limitations and evidence gaps

11) URLs and publication dates (selected primary sources prioritized to 2023–2024)

12) Conclusion

Artifacts

Citations

📚 Additional Documentation

Pn Notes

FBXL7 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: Ubiquitin Proteasome System | E3 ubiquitin and UBL ligases | Cul1 substrate receptor | F-box | LRR

Projected GO annotations (1)

Note

📄 View Raw YAML