Affinage

FIBP

Acidic fibroblast growth factor intracellular-binding protein · UniProt O43427

Length
364 aa
Mass
41.9 kDa
Annotated
2026-06-09
31 papers in source corpus 11 papers cited in narrative 11 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FIBP is an evolutionarily conserved intracellular protein, originally identified as a selective binding partner for mitogenic acidic FGF (FGF1) that distinguishes the mitogenic conformation from a non-mitogenic mutant, and it localizes predominantly to the nucleus with additional association to mitochondria and cytoplasmic membranes (PMID:9806903). Across multiple cancer contexts FIBP acts as a positive modulator of proliferation and stemness: it binds GSK3β and blocks its Tyr216 phosphorylation to activate β-catenin/TCF/cyclin D1 signaling and to control DNA-methylation–dependent stemness in colorectal cancer stem cells (PMID:30275459), and it interacts with STAT3 to enhance its transcriptional activity and induce EME1, driving lung adenocarcinoma progression and radioresistance (PMID:37564211). FIBP is also a stable subunit of a CDK5–KIAA0528 trimeric complex whose assembly requires FIBP and that supports cancer cell proliferation and migration (PMID:25096995). Beyond tumor-cell-intrinsic roles, FIBP restrains effector CD8+ T cell function by promoting cholesterol metabolism, such that its loss potentiates anti-tumor T cell killing (PMID:35501486). Consistent with a growth-restraining role in normal tissue, loss-of-function FIBP variants in human overgrowth syndromes increase the proliferative capacity of patient fibroblasts (PMID:26660953, PMID:27183861).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1998 High

    Established FIBP as a discrete intracellular protein that reads the mitogenic state of acidic FGF, providing the first molecular link between FIBP and FGF-dependent proliferation.

    Evidence Yeast two-hybrid screen and in vitro MBP-aFGF pulldown with a non-mitogenic mutant control, plus subcellular localization by immunoblot and fluorescence microscopy

    PMID:9806903

    Open questions at the time
    • No structure of the FIBP–aFGF interface
    • Functional consequence of aFGF binding for downstream signaling not tested
    • Nuclear versus membrane pools not functionally distinguished
  2. 2000 Medium

    Defined the human FIBP gene structure, chromosomal location, splice variants, and an active promoter, framing FIBP as a regulated, conserved locus.

    Evidence Genomic mapping, splice variant cloning, and luciferase promoter reporter assay

    PMID:11104667

    Open questions at the time
    • Tissue-specific roles of the two splice variants unresolved
    • Transcription factors driving the promoter not identified
  3. 2003 Medium

    Showed the FIBP ortholog is spatially expressed at canonical FGF-signaling sites in Drosophila, reinforcing a conserved developmental link to FGF biology.

    Evidence Cloning, RT-PCR, and whole-mount embryo immunostaining of DrFIBP

    PMID:12801646

    Open questions at the time
    • No genetic perturbation of DrFIBP to test FGF pathway requirement
    • Spatial expression does not establish a mechanistic role
  4. 2008 Medium

    Provided first loss-of-function evidence that FIBP supports a defined cellular output, here estradiol biosynthesis in granulosa cells.

    Evidence RNAi knockdown in primary bovine granulosa cells with estradiol production readout

    PMID:18285519

    Open questions at the time
    • Mechanism linking FIBP to steroidogenesis not defined
    • Single method, single cell type
  5. 2014 Medium

    Identified FIBP as an assembly-required subunit of a CDK5–KIAA0528 trimeric complex in non-neuronal cells and tied it to proliferation and migration.

    Evidence AP-MS interactome with SAINT, Co-IP validation, and siRNA knockdown proliferation/migration assays in breast cancer cells

    PMID:25096995

    Open questions at the time
    • Catalytic or substrate role of the complex not defined
    • How FIBP stabilizes the complex structurally unknown
  6. 2016 Medium

    Linked human FIBP loss-of-function to an overgrowth phenotype, indicating FIBP normally restrains proliferation in vivo.

    Evidence Exome/genome sequencing of patients (nonsense and in-frame insertion variants), confirmed mRNA degradation, fibroblast proliferation assays, and mouse embryo in situ hybridization

    PMID:26660953 PMID:27183861

    Open questions at the time
    • Mechanism connecting FIBP loss to fibroblast hyperproliferation not resolved
    • Brain expression role in cognitive phenotype untested functionally
  7. 2018 High

    Defined a concrete signaling mechanism: FIBP binds GSK3β to suppress its Tyr216 phosphorylation, activating β-catenin/cyclin D1 and separately controlling methylation-dependent stemness.

    Evidence shRNA knockdown, FIBP–GSK3β Co-IP, phosphorylation assay, RNA-seq/GSEA, GSK3β epistasis rescue, DNA methylation profiling, and xenografts in colorectal cancer stem cells

    PMID:30275459

    Open questions at the time
    • Whether FIBP directly possesses methyltransferase activity or recruits one is unclear
    • Relationship between the GSK3β axis and the CDK5 complex not integrated
  8. 2022 High

    Revealed a cell-extrinsic immunoregulatory role: FIBP limits effector CD8+ T cell anti-tumor function via cholesterol metabolism, identifying it as an actionable immunotherapy target.

    Evidence CRISPR/Cas9 knockout in murine and human CD8+ T cells, tumor co-culture killing, in vivo adoptive transfer in B16 melanoma, and cholesterol metabolism profiling

    PMID:35501486

    Open questions at the time
    • Molecular step by which FIBP controls cholesterol metabolism unknown
    • Whether the FGF/GSK3β/CDK5 activities operate in T cells untested
  9. 2023 Medium

    Added a transcriptional mechanism: FIBP enhances STAT3 activity to induce EME1, driving tumor progression and radioresistance.

    Evidence Reciprocal FIBP–STAT3 Co-IP, STAT3 transcriptional activity and EME1 expression assays, FIBP knockdown in vitro/in vivo, and EME1 rescue in lung adenocarcinoma

    PMID:37564211

    Open questions at the time
    • Whether FIBP binds STAT3 directly or via a complex not resolved
    • How nuclear FIBP coordinates STAT3 versus GSK3β axes unknown
  10. 2025 Low

    Extended the CDK5–FIBP complex inventory by placing USP5 and C2CD5 within it in AML cells.

    Evidence Co-immunoprecipitation coupled with mass spectrometry in AML cells

    PMID:41344512

    Open questions at the time
    • Single Co-IP/MS without functional follow-up on FIBP's role in the complex
    • Whether USP5 acts on FIBP stability untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how FIBP's distinct activities — aFGF binding, the CDK5 complex, GSK3β/β-catenin signaling, STAT3 transactivation, and cholesterol metabolism — are unified into a single biochemical function.
  • No defined catalytic activity for FIBP itself
  • No structural model integrating its multiple partners
  • Relationship between nuclear and membrane-associated pools unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 2 GO:0060089 molecular transducer activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 1 GO:0005739 mitochondrion 1
Pathway
R-HSA-1430728 Metabolism 1 R-HSA-162582 Signal Transduction 1 R-HSA-168256 Immune System 1
Complex memberships
FIBP-CDK5-KIAA0528 trimeric complex

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 FIBP (aFGF intracellular binding protein) was identified as a novel 42 kDa intracellular protein that binds selectively to mitogenic acidic FGF (aFGF) but not to the non-mitogenic mutant aFGF-K132E, indicating specificity for the mitogenic conformation. In vitro-translated FIBP bound specifically to a maltose-binding protein–aFGF fusion protein. The protein localizes predominantly to the nucleus and, to a lesser extent, to mitochondria and other cytoplasmic membranes, including post-translational association with microsomes. Yeast two-hybrid screen, in vitro binding assay (MBP-aFGF pulldown), cell-free translation + microsome association, immunoblot, fluorescence microscopy The Biochemical journal High 9806903
2000 The human FIBP gene spans >5 kb, comprises ten exons and nine introns, and maps to chromosome 11q13.1. Two splice variants exist in different tissues. Functional promoter analysis with a luciferase reporter system localized strong transcriptional activity to within 600 bp of the 5′ flanking region. Comparative analysis showed FIBP is evolutionarily conserved across human, mouse, and Drosophila. Genomic mapping, splice variant cloning and sequencing, luciferase reporter assay The Biochemical journal Medium 11104667
2003 A Drosophila FIBP homologue (DrFIBP) was cloned and characterized; it shares conserved structural architecture with human FIBP. DrFIBP is expressed during embryonic, larval, and adult stages and is spatially expressed in the developing tracheal system and ventral midline cells — two known sites of FGF signaling — as determined by whole-mount embryo immunostaining. Cloning, comparative sequence analysis, RT-PCR, whole-mount embryo immunostaining Gene Medium 12801646
2008 RNA interference-mediated inhibition of FIBP in bovine granulosa cells in vitro inhibited estradiol production, suggesting FIBP promotes estradiol biosynthesis in granulosa cells of regressing subordinate follicles. RNA interference (RNAi) knockdown in primary granulosa cells, estradiol production assay Physiological genomics Medium 18285519
2014 FIBP was identified as a novel CDK5-binding partner in non-neuronal cells. FIBP, CDK5, and KIAA0528 form a stable trimeric complex, with KIAA0528 and FIBP both required for the assembly and stability of the complex. Depletion of FIBP (or CDK5 or KIAA0528) in breast cancer cells impaired cell proliferation and decreased migration. Proteomic CDK family interactome (AP-MS with SAINT analysis), Co-IP validation, siRNA knockdown with proliferation and migration assays Molecular & cellular proteomics : MCP Medium 25096995
2016 A homozygous nonsense FIBP variant in a patient caused FIBP mRNA degradation (likely NMD) and resulted in increased proliferation capacity of the patient's fibroblasts compared with controls, linking FIBP loss-of-function to enhanced cell proliferation in the context of an overgrowth syndrome. Exome sequencing, RT-PCR (cDNA degradation), in vitro cellular proliferation assay Clinical genetics Medium 26660953
2016 An in-frame insertion in FIBP (p.H59LN) in three affected siblings with an overgrowth syndrome caused increased proliferation capacity in patient skin fibroblasts compared to controls. In situ hybridization in mouse embryos detected Fibp expression most notably in the brain, suggesting a role in cognitive development. Whole-genome genotyping, whole-exome sequencing, in vitro cellular proliferation assay, in situ hybridization in mouse embryos American journal of medical genetics. Part A Medium 27183861
2018 FIBP knockdown in colorectal cancer stem cells inhibited proliferation, enhanced chemotherapy sensitivity, and reduced stemness markers in vitro and in vivo. Mechanistically, FIBP bound to GSK3β and inhibited its phosphorylation at Tyr216, thereby activating β-catenin/TCF/cyclin D1 signaling. Additional GSK3β knockdown reversed FIBP-silencing-induced inhibition of proliferation. FIBP also regulated stemness via methylation activity dependent on GSK3β but independent of β-catenin. shRNA knockdown, Co-IP (FIBP–GSK3β interaction), phosphorylation assay, RNA-seq + GSEA, in vivo xenograft, GSK3β rescue knockdown, DNA methylation profiling Oncogenesis High 30275459
2022 FIBP knockdown in murine and human CD8+ T cells significantly enhanced T cell-mediated cancer killing in in vitro co-culture assays. Fibp knockout in murine T cells potentiated the in vivo efficacy of adoptive cell transfer in the B16 melanoma model. Mechanistically, Fibp knockout T cells exhibited reduced cholesterol metabolism, which was identified as the pathway through which FIBP inhibits effector T cell function. CRISPR/Cas9 knockout in murine and human CD8+ T cells, in vitro tumor co-culture killing assay, in vivo adoptive cell transfer (B16 tumor model), cholesterol metabolism profiling Nature medicine High 35501486
2023 FIBP interacts with transcription factor STAT3 to enhance its transcriptional activity, leading to induced expression of the downstream target gene EME1. Depletion of FIBP inhibited lung adenocarcinoma progression and radioresistance in vitro and in vivo, and the biological effects of FIBP were partially dependent on EME1. Co-IP (FIBP–STAT3 interaction), STAT3 transcriptional activity assay, EME1 expression analysis, FIBP knockdown in vitro and in vivo, EME1 rescue experiments International journal of biological sciences Medium 37564211
2025 USP5 was found to interact with a protein complex containing FIBP, C2CD5, and CDK5, as identified by co-immunoprecipitation coupled with mass spectrometry in AML cells, confirming FIBP participates in this multi-protein complex. Co-immunoprecipitation coupled with mass spectrometry Biochemical pharmacology Low 41344512

Source papers

Stage 0 corpus · 31 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2022 Genetics of the human microglia regulome refines Alzheimer's disease risk loci. Nature genetics 139 35931864
2022 A T cell resilience model associated with response to immunotherapy in multiple tumor types. Nature medicine 53 35501486
1998 Cloning of an intracellular protein that binds selectively to mitogenic acidic fibroblast growth factor. The Biochemical journal 52 9806903
2014 Proteomic analysis of the human cyclin-dependent kinase family reveals a novel CDK5 complex involved in cell growth and migration. Molecular & cellular proteomics : MCP 37 25096995
2018 FIBP knockdown attenuates growth and enhances chemotherapy in colorectal cancer via regulating GSK3β-related pathways. Oncogenesis 32 30275459
2022 Identification of Novel Risk Loci for Behçet's Disease-Related Uveitis in a Chinese Population in a Genome-Wide Association Study. Arthritis & rheumatology (Hoboken, N.J.) 27 34652073
2016 Homozygous FIBP nonsense variant responsible of syndromic overgrowth, with overgrowth, macrocephaly, retinal coloboma and learning disabilities. Clinical genetics 20 26660953
2008 Differential expression of signal transduction factors in ovarian follicle development: a functional role for betaglycan and FIBP in granulosa cells in cattle. Physiological genomics 17 18285519
2015 Identification and comparison of gonadal transcripts of testis and ovary of adult common carp Cyprinus carpio using suppression subtractive hybridization. Theriogenology 15 25772851
2016 A recessive syndrome of intellectual disability, moderate overgrowth, and renal dysplasia predisposing to Wilms tumor is caused by a mutation in FIBP gene. American journal of medical genetics. Part A 14 27183861
2000 Organization, chromosomal localization and promoter analysis of the gene encoding human acidic fibroblast growth factor intracellular binding protein. The Biochemical journal 13 11104667
2023 Genes selection using deep learning and explainable artificial intelligence for chronic lymphocytic leukemia predicting the need and time to therapy. Frontiers in oncology 12 37719021
2021 A transcriptome-wide association study identifies novel susceptibility genes for psoriasis. Human molecular genetics 11 34409462
2023 FIBP interacts with transcription factor STAT3 to induce EME1 expression and drive radioresistance in lung adenocarcinoma. International journal of biological sciences 10 37564211
2021 Shared Molecular Mechanisms between Atherosclerosis and Periodontitis by Analyzing the Transcriptomic Alterations of Peripheral Blood Monocytes. Computational and mathematical methods in medicine 8 34899963
2023 An investigation of the etiology and follow-up findings in 35 children with overgrowth syndromes, including biallelic SUZ12 variant. American journal of medical genetics. Part A 5 36919607
2022 Genetics in Behcet's Disease: An Update Review. Frontiers in ophthalmology 5 38983559
2018 Blood-based dynamic genomic signature for obsessive-compulsive disorder. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 4 30350918
2003 Characterization and tissue expression of acidic fibroblast growth factor binding protein homologue in Drosophila melanogaster. Gene 4 12801646
2023 Expanding the phenotype and genotype in Thauvin-Robinet-Faivre syndrome: A new patient with a novel variant and additional clinical findings. American journal of medical genetics. Part A 3 37218527
2025 In-silico proteomic analysis of the role of IL-4 and IL-10 in IVD degeneration: Protein-protein interaction networks for candidate prioritisation. Computational and structural biotechnology journal 2 40291541
2023 New cases of recently described Thauvin-Robinet-Faivre syndrome with a novel homozygous FIBP gene variant. American journal of medical genetics. Part A 2 37876348
2025 Identification and validation of diagnostic alternative splicing events in tumor-educated platelets for non-small cell lung cancer in patients with ground-glass opacity: a multicenter study. Translational lung cancer research 1 40386709
2025 Expanding the knowledge about Thauvin-Robinet-Faivre syndrome: a case report with novel clinical findings and review of the literature. Journal of applied genetics 1 40536757
2022 Construction of Prediction Model for Atrial Fibrillation with Valvular Heart Disease Based on Machine Learning. Reviews in cardiovascular medicine 1 39076905
2026 Transcriptomic Insights Into Alzheimer's Disease: Differentially Expressed Genes and Cholesterol Metabolism. CNS neuroscience & therapeutics 0 41854441
2025 Thauvin-Robinet-Faivre Syndrome: A FIBP Variant in an Adolescent with Segmental Overgrowth and Thyroid Carcinoma. Journal of clinical research in pediatric endocrinology 0 40099975
2025 The Identification of a Glucuronyltransferase-Related Gene, GlcAT-S, with Putative Mucus Protection and Anti-Inflammatory Effects from Gut-Damaged Drosophila by Dextran Sulfate Sodium (DSS). Biology 0 40427702
2025 From Anesthetic to Neuroprotector: Multi-Omics Reveals Ketamine's Previously Unexplored Neuroprotective Role in Alzheimer's Disease. CNS & neurological disorders drug targets 0 40908685
2025 Deciphering Alzheimer's disease transcriptomics: exploration and validation of core genes in tau and Aβ pathological models toward novel therapeutic targets. Frontiers in aging neuroscience 0 41143248
2025 Deubiquitinase USP5 promotes acute myeloid leukemia through C2CD5 stabilization and PI3K/AKT/mTOR/HIF-1α-driven glycolysis. Biochemical pharmacology 0 41344512

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