Affinage

ATP1B2

Sodium/potassium-transporting ATPase subunit beta-2 · UniProt P14415

Length
290 aa
Mass
33.4 kDa
Annotated
2026-06-09
28 papers in source corpus 14 papers cited in narrative 14 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATP1B2 (AMOG) is the β2 isoform of the Na,K-ATPase β-subunit, functioning both as an obligate auxiliary subunit of the ion pump and as a cell-surface adhesion molecule in the nervous system (PMID:1688561, PMID:1383200). It assembles stably with the α catalytic subunit — preferentially α2/α3 but not α1 in astrocytes — to form a functional sodium pump; reconstitution with α1 in Xenopus oocytes yields an active ouabain-sensitive isozyme with slightly lower maximal transport rate and external K+ affinity than the α1/β1 pump (PMID:1688561, PMID:1383200). Independent of pump activity, the glycosylated extracellular domain of β2 mediates Ca2+-independent adhesion: it binds specific neuronal subpopulations through a distinct mechanism unrelated to L1, N-CAM or HNK-1 (PMID:2457661), forms N-glycan-dependent homophilic trans-dimers (PMID:35887102), and promotes neurite outgrowth via an unidentified neuronal receptor in an isoform-specific manner not replicated by β1 (PMID:7504672). In glioma cells, re-expression of β2 increases adhesion and suppresses invasion, while its loss in astrocytes enhances invasion, linking it to control of cell motility (PMID:12887597, PMID:23887941); β2 also negatively regulates Merlin/NF2 to modulate Hippo/YAP and EGFR signaling in cerebellar granule precursors (PMID:31062247). In vivo loss or non-replaceable substitution of β2 causes apoptotic photoreceptor degeneration—cones more severely than rods—associated with reduced retinoschisin, a secreted retinal protein that interacts with β2 (PMID:8793730, PMID:40558505), and the canine SINE-insertion loss-of-function allele causes spongy degeneration with cerebellar ataxia (SDCA2) (PMID:28620085). ATP1B2 is the ACSA-2 epitope and serves as a stable astrocyte cell-surface marker in adult mouse brain (PMID:28373281).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1988 Medium

    Established that AMOG is a neuron-selective adhesion ligand, defining its activity as distinct from the major known neural adhesion systems.

    Evidence Liposome reconstitution and cell-binding assays with Fab fragment blocking in cerebellar cultures

    PMID:2457661

    Open questions at the time
    • Neuronal receptor for AMOG not identified
    • Single lab, single study
  2. 1990 High

    Identified AMOG as a Na,K-ATPase β-subunit homologue physically associated with the α2/α3 (not α1) catalytic subunit, and showed its adhesion function is independent of pump activity.

    Evidence cDNA sequencing, immunoaffinity purification, 86Rb+ uptake, blocking antibody in astrocytes

    PMID:1688561

    Open questions at the time
    • Structural basis of α-isoform selectivity not resolved
    • Adhesion receptor unidentified
  3. 1992 High

    Demonstrated AMOG/β2 is a functional pump subunit by reconstituting an active α1/β2 isozyme, and characterized the promoter elements controlling its expression.

    Evidence Xenopus oocyte cRNA expression, ouabain binding and 86Rb+ uptake, immunoprecipitation; promoter deletion/mutation transfection assays

    PMID:1377671 PMID:1383200

    Open questions at the time
    • Functional consequence of altered K+ affinity in vivo unknown
    • Transcription factors binding AMRE not identified
  4. 1993 High

    Established that the β2 extracellular domain promotes neurite outgrowth, separating this adhesion-linked function from the β1 isoform.

    Evidence L-cell substrate transfection, neurite outgrowth assay, antibody and recombinant ECD blocking

    PMID:7504672

    Open questions at the time
    • Neuronal receptor mediating outgrowth unidentified
    • Signaling downstream of receptor unknown
  5. 1996 Medium

    Showed in vivo that β2 loss causes selective apoptotic photoreceptor death with reactive gliosis, establishing a non-redundant role in retinal cell survival.

    Evidence Atp1b2 knockout mice, TUNEL, electron microscopy, immunohistochemistry

    PMID:8793730

    Open questions at the time
    • Molecular mechanism linking β2 loss to photoreceptor apoptosis not defined
    • Cell-autonomous vs glial contribution unresolved
  6. 2003 Medium

    Demonstrated a direct role for β2 in restraining glioma cell motility via increased adhesion.

    Evidence Re-expression in C6 glioma cells, Matrigel invasion and adhesion assays

    PMID:12887597

    Open questions at the time
    • Mechanism coupling β2 adhesion to reduced migration unknown
    • Single lab
  7. 2013 Medium

    Confirmed bidirectionally that β2 suppresses invasion in human glioma and astrocytes, separating this from migration and proliferation.

    Evidence Overexpression and siRNA knockdown, Matrigel invasion, scratch assay, cell counting

    PMID:23887941

    Open questions at the time
    • Downstream effectors of invasion suppression not defined
    • Single lab
  8. 2017 Medium

    Linked a natural ATP1B2 loss-of-function allele to cerebellar disease in dogs and identified ATP1B2 as the ACSA-2 astrocyte surface marker.

    Evidence Canine WGS/linkage, RT-PCR splicing analysis, IHC (SDCA2); ACSA-2 epitope mapping by overexpression/knockdown, immunoblot, scRNA-seq

    PMID:28373281 PMID:28620085

    Open questions at the time
    • Mechanism connecting protein reduction to spongy degeneration not defined
    • Human disease equivalent not established in timeline
  9. 2019 Medium

    Defined β2 as a negative regulator of Merlin/NF2–Hippo/YAP and EGFR signaling and uncovered an inverse relationship with L1CAM in glioma.

    Evidence siRNA knockdown, immunoblotting, EGF stimulation, actin imaging in granule precursors; knockdown with apoptosis/senescence assays in glioblastoma lines

    PMID:31062247 PMID:31510944

    Open questions at the time
    • Direct molecular link between β2 and Merlin not established
    • Mechanism of L1CAM regulation unknown
  10. 2022 Medium

    Established β2 as a homophilic adhesion molecule whose extracellular domain forms N-glycan-dependent trans-dimers.

    Evidence In silico docking, cell aggregation assays, trans-interaction assays with tunicamycin perturbation in CHO/MDCK cells

    PMID:35887102

    Open questions at the time
    • No experimental structure of the dimer
    • Computational docking not structurally confirmed
  11. 2025 Medium

    Showed β2 is specifically required for cone survival and cannot be functionally replaced by β1, and linked it to retinoschisin.

    Evidence Atp1b2 β1 knock-in mice, IHC, in situ hybridization, cell counting

    PMID:40558505

    Open questions at the time
    • Mechanism of β2–retinoschisin functional coupling not defined
    • Why cones are more vulnerable than rods unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the neuronal receptor mediating β2-dependent adhesion and neurite outgrowth, and the direct biochemical mechanisms linking β2 to Merlin/NF2 and retinoschisin, remain unresolved.
  • No neuronal binding partner identified
  • Direct β2–Merlin interaction not demonstrated
  • Mechanism of cell-type-specific photoreceptor degeneration unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 3 GO:0005215 transporter activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-1500931 Cell-Cell communication 2 R-HSA-382551 Transport of small molecules 2 R-HSA-162582 Signal Transduction 1
Complex memberships
Na,K-ATPase

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 AMOG (ATP1B2) is a homologue of the β-subunit of Na,K-ATPase with 40% amino acid identity to the rat brain Na,K-ATPase β subunit. Immunoaffinity-purified AMOG was associated with a 100 kDa protein comprising the α2 (and possibly α3) isoforms of the Na,K-ATPase catalytic subunit, but not α1. A monoclonal anti-AMOG antibody that blocks adhesion increased ouabain-inhibitable 86Rb+ uptake in intact cultured astrocytes, demonstrating functional association with the Na,K-ATPase pump. AMOG-mediated adhesion occurred at 4°C and in the presence of ouabain, indicating adhesion is independent of Na,K-ATPase pump activity. cDNA sequencing, immunoaffinity purification, immunoprecipitation, 86Rb+ uptake assay, monoclonal antibody blocking The Journal of cell biology High 1688561
1992 AMOG/β2 expressed by cRNA injection in Xenopus oocytes assembles with endogenous Xenopus α1 or coexpressed Torpedo α1 subunits to form a functional α1/AMOG sodium pump isozyme, as demonstrated by ouabain binding site quantification and ouabain-sensitive 86Rb+ uptake. The α1/AMOG isozyme has slightly lower maximum transport rate and apparent affinity for external K+ than the α1/β1 isozyme. Immunoprecipitation from digitonin extracts confirmed stable association between AMOG and α1 subunits. Xenopus oocyte expression system, cRNA injection, ouabain binding assay, 86Rb+ uptake assay, immunoprecipitation The Journal of biological chemistry High 1383200
1993 AMOG/β2, but not the β1 subunit of Na,K-ATPase, promotes neurite outgrowth when expressed on L-cells used as substrates for cerebellar and hippocampal neurons. This effect was specifically inhibited by anti-AMOG/β2 antibodies and a neuronal membrane fraction, and partially inhibited by the soluble recombinant extracellular domain of AMOG/β2, demonstrating that the extracellular domain mediates this function via an unknown neuronal receptor. Transfection of L-cells, neurite outgrowth assay, antibody blocking, recombinant extracellular domain inhibition The Journal of biological chemistry High 7504672
1988 Immunoaffinity-purified AMOG incorporated into liposomes binds specifically to neurons (including PC12 cells) but not to oligodendrocytes, astrocytes, or fibroblasts in cerebellar cultures. Binding was inhibited by Fab fragments of monoclonal AMOG antibodies (but not by L3 anti-carbohydrate antibodies), and was not blocked by antibodies to L1, N-CAM, or L2/HNK-1, demonstrating AMOG acts as an adhesion ligand for specific neuronal subpopulations via a distinct, independent mechanism. Liposome reconstitution assay, cell binding assay, Fab fragment inhibition The Journal of neuroscience Medium 2457661
2003 Re-expression of AMOG/β2 in AMOG/β2-negative C6 rat glioma cells by transfection increased cell adhesion and decreased migration on Matrigel compared to AMOG/β2-negative counterparts, demonstrating a direct role of AMOG/β2 in controlling glioma cell adhesion and invasion. Transfection/re-expression, Matrigel invasion assay, adhesion assay Neuropathology and applied neurobiology Medium 12887597
2013 Overexpression of AMOG in GBM cells decreased invasion without affecting migration or proliferation, while knockdown of AMOG in normal human astrocytes increased invasion, establishing a direct role for AMOG/β2 in suppressing glioma invasion. Overexpression and siRNA knockdown, Matrigel invasion assay, scratch assay, direct cell counting Neuro-oncology Medium 23887941
2019 In cerebellar granule precursor cells, β2-subunit (AMOG) knockdown resulted in increased Merlin/NF2 expression, increased YAP phosphorylation, and decreased N-Ras expression, demonstrating that β2-subunit negatively regulates Merlin/NF2 and thereby modulates Hippo/YAP signaling. β2 knockdown also altered EGFR signaling kinetics in a Merlin-dependent manner and impaired EGF-induced actin cytoskeleton reorganization. Isoform specificity was confirmed: β1 knockdown did not replicate these effects. siRNA knockdown, immunoblotting, EGF stimulation assays, actin cytoskeleton imaging Molecular neurobiology Medium 31062247
2019 Reduction of AMOG expression in human glioblastoma cells (U-87 MG, U251, SHG44) elevated L1CAM expression, accompanied by decreased cell apoptosis and senescence, establishing an inverse regulatory relationship between AMOG and L1CAM expression in glioma cells. siRNA knockdown, immunoblotting, flow cytometry (apoptosis/senescence assays) BMC cancer Medium 31510944
1996 Disruption of the AMOG/β2 gene in mice leads to apoptotic (TUNEL-positive, ultrastructurally confirmed) death of photoreceptor cells in the retina beginning around postnatal day 9 and massively by day 16, correlated with elevated GFAP in retinal astrocytes and ectopic GFAP in Müller cells, while other retinal cell types are unaffected. AMOG/β2 knockout mice, TUNEL labeling, electron microscopy, immunohistochemistry Journal of neurocytology Medium 8793730
2022 The glycosylated extracellular domain of human β2/AMOG can form energetically stable trans-interacting homodimers. CHO fibroblasts transfected with β2 formed larger cell aggregates than controls; tunicamycin treatment reduced aggregation, implicating N-glycans. Protein-protein interaction assays in MDCK and CHO cells showed β2 subunits on the cell surface interact with each other in trans, establishing β2/AMOG as a homophilic adhesion molecule. Protein docking (in silico), cell-cell aggregation assay, protein-protein interaction assay (co-culture with differentially tagged constructs), tunicamycin treatment International journal of molecular sciences Medium 35887102
1992 The cis-acting positive regulatory element AMRE (sequence GAGGCGGGG at positions -87 to -79) in the rat AMOG/Na,K-ATPase β2 subunit gene promoter enhances promoter activity and acts in a mutually compensating manner with an Sp1 element at -147 to -142, as demonstrated by transient transfection assays in multiple cell lines. Transient transfection assay, promoter deletion/mutation analysis Journal of biochemistry Medium 1377671
2017 A SINE insertion (227 bp) into the ATP1B2 gene in Belgian Shepherd (Malinois) dogs causes aberrant RNA splicing, reduced ATP1B2 protein expression in the CNS, and results in spongy degeneration with cerebellar ataxia (SDCA2), a phenotype similar to Atp1b2 knockout mice. Linkage and homozygosity mapping, whole-genome sequencing, RT-PCR (aberrant splicing), immunohistochemistry G3 (Bethesda, Md.) Medium 28620085
2025 In Atp1b2 knock-in mice (expressing β1 instead of β2 under Atp1b2 regulatory elements), cones degenerate rapidly (absent by 4 months) while rods degenerate slowly, demonstrating that β2 is specifically required for cone photoreceptor survival and cannot be fully replaced by β1. Levels of retinoschisin, a secreted retina-specific protein that directly interacts with the β2-subunit, were greatly reduced in mutant retinas, linking β2 to retinoschisin-dependent signaling. Knock-in mouse model, immunohistochemistry, in situ hybridization, cell counting Cells Medium 40558505
2017 The ACSA-2 antibody epitope was identified as ATP1B2 by overexpression and knockdown assays, immunoblotting, and immunohistochemistry, establishing ATP1B2 as a cell surface marker of astrocytes in adult mouse brain that is stably expressed across multiple CNS injury and disease models. Overexpression, siRNA knockdown, immunoblotting, immunohistochemistry, single-cell sequencing The Journal of biological chemistry Medium 28373281

Source papers

Stage 0 corpus · 28 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 The adhesion molecule on glia (AMOG) is a homologue of the beta subunit of the Na,K-ATPase. The Journal of cell biology 348 1688561
1992 The adhesion molecule on glia (AMOG/beta 2) and alpha 1 subunits assemble to functional sodium pumps in Xenopus oocytes. The Journal of biological chemistry 81 1383200
2017 An immunoaffinity-based method for isolating ultrapure adult astrocytes based on ATP1B2 targeting by the ACSA-2 antibody. The Journal of biological chemistry 76 28373281
1993 Functional characterization of beta isoforms of murine Na,K-ATPase. The adhesion molecule on glia (AMOG/beta 2), but not beta 1, promotes neurite outgrowth. The Journal of biological chemistry 62 7504672
2009 Pi3K-mTOR signaling and AMOG expression in epilepsy-associated glioneuronal tumors. Brain pathology (Zurich, Switzerland) 59 19371356
1996 Expression of the beta 1 and beta 2(AMOG) subunits of the Na,K-ATPase in neural tissues: cellular and developmental distribution patterns. Brain research bulletin 50 8736577
1988 The adhesion molecule on glia (AMOG) incorporated into lipid vesicles binds to subpopulations of neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 47 2457661
2007 Common genetic variation in TP53 and its flanking genes, WDR79 and ATP1B2, and susceptibility to breast cancer. International journal of cancer 44 17683073
2003 AMOG/beta2 and glioma invasion: does loss of AMOG make tumour cells run amok? Neuropathology and applied neurobiology 35 12887597
2013 Na⁺/K⁺-ATPase β2-subunit (AMOG) expression abrogates invasion of glioblastoma-derived brain tumor-initiating cells. Neuro-oncology 33 23887941
1996 Apoptotic cell death of photoreceptor cells in mice deficient for the adhesion molecule on glia (AMOG, the beta 2- subunit of the Na, K-ATPase). Journal of neurocytology 33 8793730
1990 The Adhesion Molecule on Glia (AMOG) Is Widely Expressed by Astrocytes in Developing and Adult Mouse Brain. The European journal of neuroscience 29 12106033
1989 Identification of a cDNA clone specific for the neural cell adhesion molecule AMOG. Journal of neuroscience research 28 2468782
2017 A SINE Insertion in ATP1B2 in Belgian Shepherd Dogs Affected by Spongy Degeneration with Cerebellar Ataxia (SDCA2). G3 (Bethesda, Md.) 22 28620085
2010 Novel SNPs in the ATP1B2 gene and their associations with milk yield, milk composition and heat-resistance traits in Chinese Holstein cows. Molecular biology reports 18 20842439
2022 Effects of icariin on alleviating schizophrenia-like symptoms by regulating the miR-144-3p/ATP1B2/mTOR signalling pathway. Neuroscience letters 17 36261079
1995 The AMOG/beta 2 subunit of Na,K-ATPase is not necessary for long-term survival of telencephalic grafts. Glia 17 8926033
2010 Expression patterns of AMOG in developing human cortex and malformations of cortical development. Epilepsy research 14 20656459
2019 Glioma malignancy is linked to interdependent and inverse AMOG and L1 adhesion molecule expression. BMC cancer 13 31510944
1992 Identification and characterization of the cis-elements regulating the rat AMOG (adhesion molecule on glia)/Na,K-ATPase beta 2 subunit gene. Journal of biochemistry 12 1377671
2019 A Functional Interaction Between Na,K-ATPase β2-Subunit/AMOG and NF2/Merlin Regulates Growth Factor Signaling in Cerebellar Granule Cells. Molecular neurobiology 11 31062247
1990 Assignment of Amog (adhesion molecule on glia) gene to mouse chromosome 11 near Zfp-3 and Asgr-1,2 and to human chromosome 17. Somatic cell and molecular genetics 11 1699290
2022 The β2-Subunit (AMOG) of Human Na+, K+-ATPase Is a Homophilic Adhesion Molecule. International journal of molecular sciences 10 35887102
1992 Production and secretion in CHO cells of the extracellular domain of AMOG/beta 2, a type-II membrane protein. Gene 9 1383096
2025 Overexpression of ATP1B2 promotes cancer cell migration and inhibits apoptosis in patients with esophageal squamous cell carcinoma. Oncology reports 1 40539436
2025 Atp1b2 Knock-In Mice Exhibit a Cone-Rod Dystrophy-Like Phenotype. Cells 0 40558505
2025 Connecting the Dots: AMOG/β2 and Its Elusive Adhesion Partner in CNS. International journal of molecular sciences 0 40943664
1994 [Morphology and development of neural transplants of AMOG-deficient mice]. Verhandlungen der Deutschen Gesellschaft fur Pathologie 0 7534017

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