AP-2 complex subunit beta · UniProt P63010
AP2B1 (β2-adaptin/CLAPB1) is the β-subunit of the clathrin-associated AP-2 adaptor complex and functions as a core mediator of clathrin-mediated endocytosis, coupling cargo and accessory proteins to clathrin-coated pit assembly (PMID:31694949, PMID:39893205). It physically engages β-arrestin1 in a cascade that drives clathrin-mediated internalization of influenza A virus, and disrupting the β-arrestin1/AP2B1 interaction with Barbadin or depleting AP2B1 sharply reduces viral uptake (PMID:31694949). AP2B1 also binds amphiphysin following its dephosphorylation by PTENα to support endocytosis in olfactory neurons (PMID:31291551), and is engaged by the GTP-dependent protein GPN3, which together with AP2S1 and clathrin light chain A modulates clathrin-coated pit invagination and EGFR internalization (PMID:39893205). In neurons, AP2B1 levels are tightly controlled translationally: FMRP represses AP2B1 mRNA, and FMRP loss elevates AP2B1 protein to enhance AP-2-mediated endocytosis of AMPA receptors including GluA2, a phenotype rescued by restoring AP2B1 to wild-type levels (PMID:40740492); AP2B1 knockdown also impairs dendritogenesis through mTOR-dependent GluA2 biosynthesis (PMID:28190237). Beyond endocytosis, AP2B1 acts as a required mediator of full-length IL-33-induced Smad3 phosphorylation through the TGF-β receptor (PMID:32977155), is transcriptionally upregulated by NRF1 in hypoxic microglia to enhance phagocytosis (PMID:35704676), and has been assigned a nuclear role transporting GAL3ST1-sulfated histone H3 to drive β-catenin-dependent transcription in gastric cancer cells (PMID:41686426). AP2B1 expression is further tuned by upstream regulators including the SLC35B4–heparan sulfate–AGRN axis (PMID:40130891) and miR-145b (PMID:39813009).
Established the genomic locus of the AP-2 β large subunit, providing the foundation for studying the human gene.
Evidence Somatic cell hybrid panel PCR mapping to chromosome 17q11.2-q12
Placed AP2B1 upstream of mTOR-dependent GluA2 biosynthesis in neuronal development, extending its role beyond endocytic machinery to dendritogenesis.
Evidence shRNA knockdown in rat hippocampal neurons with GluA2 and S6K1 rescue, mTOR pathway assays
Defined AP2B1 as the direct adaptor link between β-arrestin1 and clathrin-mediated internalization of influenza A virus, validated pharmacologically and by knockdown.
Evidence Co-immunoprecipitation, siRNA knockdown, Barbadin inhibitor, viral internalization assay
Showed that AP2B1 recruitment of amphiphysin is gated by PTENα-mediated dephosphorylation, linking phosphatase signaling to endocytosis in olfactory neurons.
Evidence In vitro dephosphorylation assay, co-IP/pulldown, mouse overexpression with behavioral readout
Identified an endocytosis-independent role for AP2B1 as a required mediator of FLIL33-induced Smad3 phosphorylation via the TGF-β receptor.
Evidence siRNA knockdown, overexpression, Smad3 phospho-Western, anti-TGF-β neutralization
Demonstrated transcriptional control of AP2B1 by NRF1 under hypoxia, linking its abundance to microglial phagocytosis and BBB disruption.
Evidence Hypobaric hypoxia mouse model, cultured microglia, NRF1 promoter assays, PLX5622 depletion
Resolved how AP2B1 protein levels are translationally constrained by FMRP, mechanistically connecting AP2B1 dosage to AMPA receptor endocytosis in fragile X syndrome models.
Evidence Surface proteome mass spectrometry, FMRP-mRNA association, polysome assay, shRNA rescue, AMPAR endocytosis assay
Showed that GPN3 binds AP2B1/AP2S1 and clathrin light chain A in a GTP-dependent manner to restrain coated-pit invagination and EGFR endocytosis, identifying a new modulator of AP2B1 function.
Evidence Co-IP, co-localization, coated-pit invagination assay, EGFR endocytosis assay, GTP manipulation
Embedded AP2B1 in an upstream regulatory axis whereby SLC35B4-driven heparan sulfate biosynthesis and AGRN control AP2B1 expression to enable IAV internalization.
Evidence Sequential siRNA knockdown of pathway components, AP2B1 expression measurement, viral internalization assay
Proposed an unprecedented nuclear histone-transport role for AP2B1, shuttling sulfated histone H3 to drive β-catenin transcription and metastasis in gastric cancer.
Evidence Nuclear transport assay with AP2B1, ChIP for histone marks, reporter assays, in vivo metastasis models
Identified miR-145b as a direct negative regulator of AP2B1, connecting its downregulation to noise-induced hearing loss.
Evidence Luciferase 3'UTR reporter, RT-qPCR/Western, in vivo miR-145b depletion, auditory brainstem response
Flagged a redox-sensitive, low-accessibility cysteine (Cys818) on AP2B1 responsive to oxidative stress, hinting at a possible post-translational regulatory site.
Evidence Chemical proteomics with fluorinated porphyrin probe, MS site ID, live-cell labeling under diamide stress
| Year | Finding | Method | Journal | Conf | PMIDs |
|---|---|---|---|---|---|
| 1995 | AP2B1 (CLAPB1/AP2 beta large subunit) was chromosomally mapped to human chromosome 17q11.2-q12 by PCR amplification from rodent-human hybrid DNA panels, establishing its genomic locus. | Somatic cell hybrid panel PCR mapping | Genomics | Medium | 8595912 |
| 2017 | Knockdown of AP2B1 (AP2b1/β2-adaptin) in developing rat hippocampal neurons reduced dendrite number and decreased AMPA receptor subunit GluA2 levels via inhibition of mTOR. Overexpression of GluA2 or the mTOR effector p70S6K (S6K1) rescued the dendritic arbor defect, placing AP2B1 upstream of mTOR-dependent GluA2 biosynthesis in dendritogenesis. | shRNA knockdown in rat hippocampal neurons, rescue by GluA2 overexpression and S6K1 restoration, mTOR pathway assays | Molecular neurobiology | Medium | 28190237 |
| 2019 | β-arrestin1 physically interacts with AP2B1 (the β2-subunit of the AP-2 clathrin adaptor complex), and this FFAR2–β-arrestin1–AP2B1 signaling cascade is required for efficient clathrin-mediated endocytosis of influenza A virus. siRNA knockdown of AP2B1 or treatment with Barbadin (an inhibitor of the β-arrestin1/AP2B1 interaction) dramatically reduced IAV internalization. | Co-immunoprecipitation, siRNA knockdown, Barbadin inhibitor treatment, viral internalization assay | Journal of virology | High | 31694949 |
| 2019 | PTENα directly dephosphorylates the endocytic protein amphiphysin and promotes its binding to AP2B1 in olfactory bulb neurons, thereby regulating endocytosis and olfactory function. | In vitro dephosphorylation assay, co-immunoprecipitation/pulldown, mouse overexpression model with behavioral readout | FASEB journal | Medium | 31291551 |
| 2019 | Wnt16 activates the planar cell polarity (PCP)/JNK pathway by interacting mainly with AP2B1 (and to a lesser extent Ror2 and CD146) in chondrocytes, subsequently inducing PTHrP expression through the phospho-Raptor mTORC1 pathway to inhibit chondrocyte hypertrophy. | Co-immunoprecipitation/interaction assays, transgenic mouse and conditional KO models, intra-articular adenoviral injection, 3D chondrocyte pellet culture, biochemical pathway analysis | Annals of the rheumatic diseases | Medium | 30745310 |
| 2020 | Full-length IL-33 (FLIL33) overexpression increased levels of AP2B1 and AP2A1 subunits of the AP-2 complex, and siRNA-mediated knockdown of AP2B1 blocked FLIL33-induced Smad3 phosphorylation; conversely, AP2B1 overexpression alone induced Smad3 phosphorylation independent of TGF-β, demonstrating AP2B1 as a required mediator of FLIL33-driven Smad3 signaling through a TGF-β-independent but TGF-β receptor-dependent mechanism. | siRNA knockdown, overexpression, Western blotting for Smad3 phosphorylation, anti-TGF-β antibody neutralization | Cellular immunology | Medium | 32977155 |
| 2022 | NRF1 transcriptionally upregulates AP2B1 in microglia under hypoxia to enhance phagocytic function, contributing to blood-brain barrier disruption in high-altitude cerebral edema. | In vivo hypobaric hypoxia mouse model, in vitro cultured microglia, transcriptional regulation assays (NRF1 on AP2B1 promoter), microglia depletion by PLX5622 | Journal of molecular cell biology | Medium | 35704676 |
| 2025 | GPN3 interacts with AP2B1 and AP2S1 (clathrin-mediated endocytosis modulators) and with clathrin light chain A (CLTA); upregulation of GPN3 inhibits clathrin-coated pit invagination and reduces EGFR endocytosis, thereby prolonging EGFR signaling on the cell surface. This interaction and GPN3's effects on endocytosis are GTP-dependent. | Co-immunoprecipitation, co-localization imaging, clathrin-coated pit invagination assay, EGFR endocytosis assay, GTP abundance manipulation | Cell death discovery | Medium | 39893205 |
| 2025 | FMRP associates with and represses translation of AP2B1 mRNA; loss of FMRP in fragile X syndrome models leads to increased steady-state AP2B1 protein levels, enhanced AP-2-mediated endocytosis of AMPA receptors (including dendritic GluA2), and shRNA knockdown of AP2B1 to wild-type levels in FMRP-deficient neurons rescues this endocytosis phenotype. | Quantitative mass spectrometry of surface proteome, FMRP-mRNA association assay, polysome/translation assay, shRNA rescue in FMRP-deficient neurons, AMPA receptor endocytosis assay | iScience | High | 40740492 |
| 2025 | SLC35B4-mediated UDP-xylose transport promotes heparan sulfate biosynthesis, which regulates the homeostasis of the HSPG member AGRN, and AGRN in turn controls the expression level of AP2B1 to facilitate clathrin-mediated endocytosis of influenza A virus. The SLC35B4–XYLT2–B4GALT7–EXT1/2–AGRN–AP2B1 axis is required for efficient IAV internalization. | siRNA knockdown of pathway components, AP2B1 expression level measurement, viral internalization assay, AGRN protein homeostasis assays | mBio | Medium | 40130891 |
| 2025 | GAL3ST1-sulfated histone H3 (H3Y99sulf) is translocated to the nucleus via AP2B1 in gastric cancer cells, where it recruits KAT2A to establish H3K56 acetylation and activate β-catenin transcription, driving epithelial-mesenchymal transition and metastasis. | Mechanistic biochemical assays, nuclear transport assay with AP2B1, ChIP for histone marks, transcriptional reporter assays, in vivo metastasis models | Cancer research | Medium | 41686426 |
| 2025 | miR-145b targets AP2B1 mRNA and negatively regulates its expression in mouse cochleae; permanent threshold shift (PTS) noise exposure increased miR-145b and decreased AP2B1 expression, and depletion of miR-145b alleviated auditory threshold shifts and outer hair cell loss by upregulating AP2B1. | Luciferase reporter assay (miR-145b targeting Ap2b1 3'UTR), RT-qPCR and western blotting, in vivo miR-145b depletion, auditory brainstem response measurement | Cell biochemistry and biophysics | Medium | 39813009 |
| 2025 | A fluorinated porphyrin-based thiol-reactive probe identified Cys818 of AP2B1 as a cysteine residue with very low solvent accessibility (relative solvent accessible area 0.02) that is sensitive to protein interactions induced by diamide-induced oxidative stress in live cells. | Chemical proteomics with fluorinated porphyrin probe, mass spectrometry site identification, live-cell labeling under diamide stress | Innovation | Low | 41626552 |
| Year | Title | Journal | Citations | PMID |
|---|---|---|---|---|
| 2002 | Targets of gene amplification and overexpression at 17q in gastric cancer. | Cancer research | 165 | 11980659 |
| 2019 | Wnt16 attenuates osteoarthritis progression through a PCP/JNK-mTORC1-PTHrP cascade. | Annals of the rheumatic diseases | 95 | 30745310 |
| 2020 | The G Protein-Coupled Receptor FFAR2 Promotes Internalization during Influenza A Virus Entry. | Journal of virology | 78 | 31694949 |
| 2019 | Endo-lysosomal proteins and ubiquitin CSF concentrations in Alzheimer's and Parkinson's disease. | Alzheimer's research & therapy | 74 | 31521194 |
| 2019 | Circular RNA NF1-419 enhances autophagy to ameliorate senile dementia by binding Dynamin-1 and Adaptor protein 2 B1 in AD-like mice. | Aging | 67 | 31860870 |
| 2010 | Analysis of chemotherapy response programs in ovarian cancers by the next-generation sequencing technologies. | Gynecologic oncology | 57 | 20181382 |
| 2022 | Cerebrospinal fluid biomarker panel of synaptic dysfunction in Alzheimer's disease and other neurodegenerative disorders. | Alzheimer's & dementia : the journal of the Alzheimer's Association | 45 | 36239248 |
| 2022 | NRF1-mediated microglial activation triggers high-altitude cerebral edema. | Journal of molecular cell biology | 43 | 35704676 |
| 2022 | Cerebrospinal Fluid Biomarkers of Synaptic Dysfunction are Altered in Parkinson's Disease and Related Disorders. | Movement disorders : official journal of the Movement Disorder Society | 43 | 36504237 |
| 2018 | Haplotype-based genome-wide association study identifies loci and candidate genes for milk yield in Holsteins. | PloS one | 42 | 29447209 |
| 2018 | A comprehensive transcriptome analysis of skeletal muscles in two Polish pig breeds differing in fat and meat quality traits. | Genetics and molecular biology | 41 | 29658965 |
| 2021 | ZHX2 promotes HIF1α oncogenic signaling in triple-negative breast cancer. | eLife | 38 | 34779768 |
| 2016 | Existence of Neural Crest-Derived Progenitor Cells in Normal and Fuchs Endothelial Dystrophy Corneal Endothelium. | The American journal of pathology | 36 | 27639969 |
| 2009 | Otitis media: a genome-wide linkage scan with evidence of susceptibility loci within the 17q12 and 10q22.3 regions. | BMC medical genetics | 32 | 19728873 |
| 2017 | Identification of New Tumor Suppressor Genes in Triple-Negative Breast Cancer. | Cancer research | 29 | 28724549 |
| 2017 | Adaptor Complex 2 Controls Dendrite Morphology via mTOR-Dependent Expression of GluA2. | Molecular neurobiology | 28 | 28190237 |
| 2017 | Differential Peripheral Proteomic Biosignature of Fluoxetine Response in a Mouse Model of Anxiety/Depression. | Frontiers in cellular neuroscience | 28 | 28860968 |
| 2020 | Alzheimer Disease Pathology-Associated Polymorphism in a Complex Variable Number of Tandem Repeat Region Within the MUC6 Gene, Near the AP2A2 Gene. | Journal of neuropathology and experimental neurology | 26 | 31748784 |
| 2016 | Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach. | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences | 21 | 27112992 |
| 2022 | Endosomal-Lysosomal and Autophagy Pathway in Alzheimer's Disease: A Systematic Review and Meta-Analysis. | Journal of Alzheimer's disease : JAD | 20 | 35754279 |
| 2016 | Investigating the specific core genetic-and-epigenetic networks of cellular mechanisms involved in human aging in peripheral blood mononuclear cells. | Oncotarget | 18 | 26895224 |
| 2024 | Proteomic characterization of hUC-MSC extracellular vesicles and evaluation of its therapeutic potential to treat Alzheimer's disease. | Scientific reports | 17 | 38472335 |
| 2018 | Associations of genetic variants in endocytic trafficking of epidermal growth factor receptor super pathway with risk of nonsyndromic cleft lip with or without cleft palate. | Molecular genetics & genomic medicine | 14 | 30411541 |
| 2020 | The interactome of the prostate-specific protein Anoctamin 7. | Cancer biomarkers : section A of Disease markers | 12 | 32176628 |
| 2013 | The effect of clozapine on mRNA expression for genes encoding G protein-coupled receptors and the protein components of clathrin-mediated endocytosis. | Psychiatric genetics | 11 | 23811784 |
| 2021 | Endocytic Protein Defects in the Neural Crest Cell Lineage and Its Pathway Are Associated with Congenital Heart Defects. | International journal of molecular sciences | 9 | 34445520 |
| 2020 | Full-length IL-33 regulates Smad3 phosphorylation and gene transcription in a distinctive AP2-dependent manner. | Cellular immunology | 9 | 32977155 |
| 1995 | Chromosome localization of human genes for clathrin adaptor polypeptides AP2 beta and AP50 and the clathrin-binding protein, VCP. | Genomics | 9 | 8595912 |
| 2023 | Digital color-coded molecular barcoding reveals dysregulation of common FUS and FMRP targets in soma and neurites of ALS mutant motoneurons. | Cell death discovery | 7 | 36702823 |
| 2019 | PTENα regulates endocytosis and modulates olfactory function. | FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 7 | 31291551 |
| 2023 | Screening and Bioinformatics Analyses of Key miRNAs Associated with Toll-like Receptor Activation in Gastric Cancer Cells. | Medicina (Kaunas, Lithuania) | 6 | 36984512 |
| 2025 | Cellular SLC35B4 promotes internalization during influenza A virus entry. | mBio | 4 | 40130891 |
| 2024 | LINC08148 promotes the caveola-mediated endocytosis of Zika virus through upregulating transcription of Src. | Journal of virology | 4 | 38742902 |
| 2023 | AI Machine Learning Technique Characterizes Potential Markers of Depression in Two Animal Models of Depression. | Brain sciences | 4 | 37239235 |
| 2025 | GTPase GPN3 facilitates cell proliferation and migration in non-small cell lung cancer by impeding clathrin-mediated endocytosis of EGFR. | Cell death discovery | 3 | 39893205 |
| 2024 | Synaptic Vesicle-Related Proteins and Ubiquilin 2 in Cortical Synaptosomes Mediate Cognitive Impairment in Vascular Dementia Rats. | Molecular neurobiology | 3 | 38990251 |
| 2025 | FMRP-dependent translational control negatively regulates adapter protein complex 2-mediated endocytosis. | iScience | 2 | 40740492 |
| 2011 | Identification of 129S6/SvEvTac-specific polymorphisms on mouse chromosome 11. | DNA and cell biology | 2 | 21988490 |
| 2025 | Associations between fluid biomarkers and PET imaging ([ 11 C]UCB-J) of synaptic pathology in Alzheimer's disease. | bioRxiv : the preprint server for biology | 1 | 40236111 |
| 2025 | Sex-dependent epigenetic disruption of YY1 binding by prenatal BPA exposure downregulates Matr3 and alters Agap1 splicing in the offspring hippocampus. | Biology of sex differences | 1 | 40790242 |
| 2025 | Associations between fluid biomarkers and PET imaging ([11C]UCB-J) of synaptic pathology in Alzheimer's disease. | Alzheimer's & dementia : the journal of the Alzheimer's Association | 1 | 40878905 |
| 2026 | GAL3ST1-Mediated Histone Tyrosine Sulfation Induced by Cancer-Associated Fibroblasts Promotes Gastric Cancer Metastasis. | Cancer research | 0 | 41686426 |
| 2025 | miR-145b/AP2B1 Axis Contributes to Noise-induced Sensorineural Hearing Loss In a Male Mouse Model. | Cell biochemistry and biophysics | 0 | 39813009 |
| 2025 | One-step labeling with a fluorinated porphyrin-based probe enables in situ imaging and profiling of the thiol proteome. | Innovation (Cambridge (Mass.)) | 0 | 41626552 |
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