Affinage

ERBIN

Erbin · UniProt Q96RT1

Length
1412 aa
Mass
158.3 kDa
Annotated
2026-04-28
100 papers in source corpus 38 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ERBIN is a multidomain scaffolding protein of the LAP (LRR and PDZ) family that orchestrates epithelial polarity, receptor tyrosine kinase stability, and suppression of multiple mitogenic and inflammatory signaling cascades. Its PDZ domain directly binds the C-terminus of ErbB2/HER2, recruiting HSP90 to stabilize ErbB2 and directing the receptor to basolateral membranes—functions essential for peripheral nerve myelination and ErbB2-dependent tumorigenesis (PMID:10878805, PMID:19458253, PMID:25288731). The N-terminal leucine-rich repeat (LRR) domain binds activated Ras and displaces Raf from the Ras–Shoc2–Raf and KSR1 scaffold complexes, thereby suppressing ERK signaling downstream of desmoglein-1 and in colorectal epithelium, while the same domain interacts with Nod2 CARD domains to inhibit NF-κB activation (PMID:12379659, PMID:16301319, PMID:29980571, PMID:16203728). A Smad-interacting domain adjacent to the PDZ domain sequesters phospho-Smad2/3 from Smad4 to attenuate TGF-β transcriptional responses—a mechanism further modulated by SARA competition and STAT3 complex formation, whose disruption by loss-of-function ERBB2IP mutations causes dysregulated Th2 immune responses (PMID:17591701, PMID:21878490, PMID:28126831).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2000 High

    The identification of ERBIN as a specific PDZ-domain partner of ErbB2 that directs its basolateral localization established ERBIN as a receptor-targeting scaffold rather than a generic adaptor.

    Evidence Co-IP, in vitro binding, mutagenesis of ErbB2 C-terminal PDZ-binding motif, immunofluorescence in epithelial cells

    PMID:10878805

    Open questions at the time
    • Whether ERBIN interacts with other ErbB family members was unresolved
    • Mechanism by which ERBIN itself reaches the basolateral membrane was unknown
  2. 2001 High

    Discovery that ERBIN's PDZ domain engages p120-catenin relatives (delta-catenin, ARVCF, p0071) and hemidesmosomal components revealed it as a broad junction-associated scaffold linking receptor and adhesion complexes.

    Evidence Phage display, Co-IP from neurons, yeast two-hybrid, dominant-negative disruption of monolayer integrity

    PMID:11375975 PMID:11711544 PMID:11821434

    Open questions at the time
    • Functional hierarchy between ERBIN's receptor-binding and adhesion-binding roles was unresolved
    • Whether ERBIN loss disrupts junctions in vivo was untested
  3. 2002 High

    Structural determination of the ERBIN PDZ domain at atomic resolution revealed an unusual β2-β3 loop that confers dual class I/II ligand recognition, explaining its broad but selective binding repertoire.

    Evidence X-ray crystallography at 1.25 Å (ErbB2 peptide complex) and NMR with alanine scanning mutagenesis

    PMID:12444095 PMID:12446668

    Open questions at the time
    • Structure of the full-length protein or the LRR domain was not determined
    • How phosphorylation dynamically regulates ligand switching in vivo was untested
  4. 2002 High

    The discovery that ERBIN binds activated Ras and disrupts the Ras–Raf interaction established a signaling-suppressive function independent of its receptor-scaffolding role.

    Evidence Co-IP with active Ras, reporter assays, siRNA knockdown enhancing ERK activation in PC12 cells

    PMID:12379659

    Open questions at the time
    • Which domain mediates Ras binding was unresolved
    • Physiological context for this ERK-suppressive role was unclear
  5. 2005 High

    Mapping the ERK-suppressive mechanism to the LRR domain's disruption of the Shoc2–Ras–Raf scaffold, and simultaneously discovering LRR-mediated inhibition of Nod2/NF-κB signaling, revealed the LRR as a multi-pathway signaling suppressor.

    Evidence LRR domain mapping, shRNA, Erbin-null MEFs with MDP stimulation, NF-κB reporters

    PMID:16203728 PMID:16301319

    Open questions at the time
    • Whether LRR simultaneously engages Ras and Nod2 or uses distinct surfaces was unknown
    • In vivo inflammatory phenotypes of Erbin-null animals were incompletely characterized
  6. 2007 High

    Identification of a Smad-interacting domain (SID) adjacent to the PDZ domain that sequesters phospho-Smad2/3 from Smad4 established ERBIN as a negative regulator of TGF-β signaling through a third, mechanistically distinct domain.

    Evidence Co-IP, shRNA, Xenopus gain/loss-of-function, splice isoform lacking SID fails to inhibit TGF-β

    PMID:17591701

    Open questions at the time
    • How ERBIN is recruited to the TGF-β receptor complex was unknown
    • Whether SID and PDZ domain functions are coordinated was unresolved
  7. 2008 High

    Demonstration that palmitoylation at Cys14/16 is required for plasma membrane targeting resolved how ERBIN itself reaches the membrane, complementing its LRR-dependent basolateral sorting.

    Evidence C14S/C16S mutagenesis with localization readout in transfected cells

    PMID:18498353

    Open questions at the time
    • Identity of the palmitoyltransferase(s) responsible was unknown
    • Whether palmitoylation is dynamically regulated was untested
  8. 2008 High

    Erbin was placed upstream of delta-catenin in dendritic morphogenesis through genetic epistasis, demonstrating a neuronal developmental function beyond synapse-specific roles.

    Evidence shRNA/KO in hippocampal neurons, rescue experiments showing delta-catenin OE rescues Erbin loss but not vice versa

    PMID:18614673

    Open questions at the time
    • Molecular mechanism by which ERBIN controls delta-catenin localization was unresolved
    • Whether this extends to in vivo dendritic architecture was unknown
  9. 2009 High

    Erbin-null and PDZ-deletion mice established that ERBIN stabilizes ErbB2 protein in Schwann cells and is required for NRG1-dependent peripheral myelination, providing the first in vivo physiological requirement.

    Evidence Erbin-null and erbin-ΔC/ΔC knock-in mice, electron microscopy, electrophysiology of sciatic nerves

    PMID:19458253

    Open questions at the time
    • Whether ERBIN stabilizes ErbB2 through direct chaperone recruitment or prevention of degradation was unresolved
  10. 2010 High

    Discovery that ERBIN simultaneously complexes with MuSK and ErbB2 at the neuromuscular junction linked agrin and neuregulin signaling through a single scaffold.

    Evidence Co-IP of MuSK-ERBIN-ErbB2 ternary complex, siRNA reducing AChR aggregate density in primary myotubes

    PMID:20463225

    Open questions at the time
    • Whether ERBIN is required for NMJ formation in vivo was untested
    • Stoichiometry of the MuSK-ERBIN-ErbB2 complex was unknown
  11. 2011 High

    Identification of SARA as a competitor for ERBIN's Smad-binding surface provided a mechanism for dynamic regulation of TGF-β signal attenuation at endosomes.

    Evidence Co-IP, domain mapping of SARA-ERBID and ERBIN-SSID, competition assays reversing ERBIN's inhibition of Smad-dependent transcription

    PMID:21878490

    Open questions at the time
    • Whether SARA-ERBIN competition operates in specific tissue contexts was unresolved
    • Kinetic parameters of competitive binding were not determined
  12. 2013 High

    Cell-type-specific studies in PV interneurons revealed that ERBIN stabilizes TARP γ-2 to maintain surface AMPAR expression, establishing a distinct synaptic mechanism in inhibitory circuits.

    Evidence PV-specific conditional KO, mEPSC recordings, Co-IP, domain deletion attenuating surface AMPAR

    PMID:23354328

    Open questions at the time
    • Whether ERBIN stabilizes TARP γ-2 through preventing ubiquitination or other degradation pathways was unknown
    • Role in other interneuron subtypes was untested
  13. 2013 High

    Linking desmoglein-1 to ERBIN-mediated suppression of Ras-Shoc2-Raf signaling in keratinocyte differentiation unified adhesion and ERK-suppressive functions in a single physiological axis.

    Evidence Y2H, Co-IP showing DSG1 enhances ERBIN-SHOC2 interaction, siRNA epistasis, patient biopsy analysis

    PMID:23524970

    Open questions at the time
    • Whether other desmosomal cadherins similarly engage ERBIN was unknown
    • Structural basis for DSG1-dependent modulation of ERBIN-SHOC2 was unresolved
  14. 2014 High

    Co-immunoprecipitation of an ERBIN-ErbB2-HSP90 ternary complex and impaired ErbB2-driven tumorigenesis in erbin-ΔC/ΔC MMTV-neu mice resolved that ERBIN stabilizes ErbB2 by recruiting HSP90, with direct oncogenic consequences.

    Evidence Co-IP of ternary complex, MMTV-neu × erbin-ΔC/ΔC genetic cross, proliferation assays

    PMID:25288731

    Open questions at the time
    • Whether ERBIN-HSP90 interaction is direct or bridged by ErbB2 was unclear
    • How ubiquitin-dependent turnover of ERBIN itself (by SAG-βTrCP) feeds back on ErbB2 stability in vivo was incompletely explored
  15. 2017 High

    Human loss-of-function ERBB2IP mutations causing impaired STAT3-ERBIN-Smad2/3 complex formation and dysregulated Th2 responses linked ERBIN's TGF-β-suppressive mechanism to human immune disease.

    Evidence Patient-derived cells with ERBB2IP mutations, Co-IP of STAT3-ERBIN-SMAD2/3, nuclear fractionation showing unconstrained pSmad2/3

    PMID:28126831

    Open questions at the time
    • Full clinical spectrum of ERBB2IP deficiency was not delineated
    • Whether other LAP family members compensate in immune cells was unknown
  16. 2018 High

    Discovery that ERBIN displaces KSR1 from the RAF-MEK-ERK complex added a second, mechanistically distinct node of ERK pathway suppression beyond Shoc2 disruption.

    Evidence Co-IP of ERBIN-KSR1, Erbin/Apc double-KO mice with accelerated colorectal tumorigenesis and reduced survival

    PMID:29980571

    Open questions at the time
    • Whether ERBIN engages KSR1 and Shoc2 simultaneously or competitively was unresolved
    • Domain on ERBIN mediating KSR1 interaction was not mapped
  17. 2019 High

    Triple knockout of Scribble, Erbin, and Lano demonstrated that LAP proteins redundantly maintain epithelial polarity through a conserved LAPSDa domain that binds Llgl, contextualizing ERBIN within a polarity module.

    Evidence Triple KO in epithelial cells, domain rescue, junction disorganization and polarity marker mislocalization

    PMID:31147384

    Open questions at the time
    • Relative individual contributions of each LAP protein in different tissues were incompletely defined
    • Structural basis of LAPSDa-Llgl interaction was lacking
  18. 2024 High

    Platelet/megakaryocyte-specific ERBIN deletion revealed a metabolic role: loss of ERBIN-ESAM interaction increases mitochondrial oxidative phosphorylation and acyl-carnitine secretion, promoting B cell antitumor immunity.

    Evidence MK-specific Erbin KO mice, Co-IP of ERBIN-ESAM, metabolomics, mitochondrial assays, in vivo metastasis models

    PMID:38232736

    Open questions at the time
    • Mechanism linking ERBIN-ESAM to mitochondrial activity was not molecularly defined
    • Whether this metabolic function operates in non-hematopoietic cells was unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length structural model of ERBIN and the basis for simultaneous engagement of its LRR, SID, and PDZ domains with distinct partners remain unresolved; how tissue-specific isoforms and post-translational turnover (palmitoylation, SAG/βTrCP-mediated ubiquitination, VCPIP1-mediated deubiquitination) are dynamically coordinated in vivo is unknown.
  • No full-length structure or cryo-EM model exists
  • Dynamic regulation of multi-domain engagement is unexplored
  • In vivo consequences of ERBIN post-translational modifications beyond palmitoylation are poorly characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 9 GO:0098772 molecular function regulator activity 7
Localization
GO:0005886 plasma membrane 4 GO:0005768 endosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 10 R-HSA-112316 Neuronal System 6 R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1500931 Cell-Cell communication 3
Partners
CACNA1DCTNND2ERBB2ESAMKSR1NOD2SHOC2SMAD3
Complex memberships
ErbB2-ERBIN-HSP90 complexLAP polarity module (Scribble/Erbin/Lano)MuSK-ERBIN-ErbB2 complexSTAT3-ERBIN-SMAD2/3 complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 ERBIN (ERBB2 interacting protein) was identified as a PDZ domain-containing protein that directly and specifically interacts with the C-terminus of ERBB2/HER2 via its PDZ domain, and colocalizes with ERBB2/HER2 at the lateral membrane of epithelial cells; mutation of the ERBIN-binding site in ERBB2/HER2 leads to mislocalization of the receptor away from the basolateral membrane. Co-immunoprecipitation, in vitro binding, immunofluorescence co-localization, mutagenesis of binding site Nature cell biology High 10878805
2001 The Erbin PDZ domain interacts with ARVCF and delta-catenin at their C-terminal PDZ-binding motifs (DSWV-COOH), and Erbin associates with the cadherin-catenin complex through these interactions in vivo; endogenous delta-catenin and Erbin co-immunoprecipitate from neurons. C-terminal phage peptide library display, in vitro peptide binding assays, Co-IP, co-localization, mutagenesis The Journal of biological chemistry High 11821434
2001 Erbin is concentrated at postsynaptic membranes at the neuromuscular junction and in the CNS, interacts specifically with ErbB2 (not ErbB3 or ErbB4), increases ErbB2 surface expression, and interacts with PSD-95 in transfected cells and synaptosomes. Co-immunoprecipitation, biotin labeling of surface proteins, immunostaining of postsynaptic membranes The Journal of biological chemistry Medium 11279080
2001 Erbin interacts with p0071 (plakophilin-4) in a PDZ domain-dependent manner, and both proteins colocalize in desmosomes of epithelial cells; disruption of this interaction by a dominant-negative approach impairs epithelial cell monolayer integrity. Yeast two-hybrid, in vitro binding, Co-IP, immunofluorescence co-localization, dominant-negative disruption The Journal of biological chemistry High 11711544 12047349
2001 ERBIN interacts with eBPAG1 (bullous pemphigoid antigen 1) via its N-terminus and with the cytoplasmic domain of integrin β4 subunit, linking it to hemidesmosome components. Yeast two-hybrid, in vitro binding The Journal of biological chemistry Medium 11375975
2002 Crystal structure of the human Erbin PDZ domain bound to the ErbB2 C-terminal peptide (EYLGLDVPV) at 1.25 Å resolution revealed a novel mode of class II ligand recognition by a class I PDZ domain; phosphorylation of tyrosine at position -7 of ErbB2 abolishes its interaction with the Erbin PDZ domain. X-ray crystallography at 1.25 Å resolution, binding assays The Journal of biological chemistry High 12444095
2002 NMR structure of the Erbin PDZ domain in complex with a high-affinity peptide ligand; alanine and homolog scanning mutagenesis identified that the β2-β3 loop provides a binding pocket for residue at position -4 that is specific to Erbin's unusually long loop, determining ligand specificity. NMR structure determination, phage display, binding affinity measurements, alanine scanning mutagenesis The Journal of biological chemistry High 12446668
2002 Erbin is a negative regulator of the Ras-Raf-ERK signaling pathway: it associates with active (but not inactive) Ras and disrupts the Ras-Raf interaction in vitro and in vivo, thereby inhibiting ERK (but not Akt) activation; siRNA knockdown of Erbin enhances ERK activation and NGF-induced neuronal differentiation. Reporter assays, co-immunoprecipitation, in vitro interaction assay, siRNA knockdown, PC12 differentiation assay The Journal of biological chemistry High 12379659
2005 Erbin inhibits Raf activation by disrupting the Sur-8 (Shoc2)-Ras-Raf scaffold complex via its N-terminal LRR domain; expression of Erbin attenuated Sur-8 interactions with active Ras and Raf, while Erbin-shRNA increased these interactions and ERK activation. Co-immunoprecipitation, shRNA knockdown, reporter assays, LRR domain mapping The Journal of biological chemistry High 16301319
2005 Erbin interacts directly with Nod2 (specifically requiring the LRR domain of Erbin and the CARD domains of Nod2), inhibits Nod2-dependent NF-κB activation and cytokine secretion; Erbin-/- mouse embryo fibroblasts show increased sensitivity to muramyl dipeptide. Biochemical screen, in vitro binding, Co-IP, overexpression and Erbin-/- MEF knockout studies, NF-κB reporter assay The Journal of biological chemistry High 16203728
2006 Erbin interacts with Nod2 via yeast two-hybrid and Co-IP; Erbin's LRR domain and Nod2's CARD domains are necessary; no significant interaction with inactive or Crohn's disease-associated frameshift mutants of Nod2; bacterial (Shigella) infection alters Erbin/Nod2 complex dynamics; shRNA knockdown of Erbin negatively influences Nod2/MDP-mediated NF-κB activation. Yeast two-hybrid, Co-IP, immunofluorescence, shRNA knockdown, NF-κB reporter Infection and immunity High 16714539
2007 Erbin interacts specifically with Smad3 (and to lesser extent Smad2) through a novel Smad-interacting domain (SID) adjacent to its PDZ domain; Erbin sequesters phospho-Smad2/3 away from Smad4 to negatively modulate TGF-β transcriptional responses; an alternatively spliced isoform lacking the SID fails to inhibit TGF-β responses. Co-IP, shRNA knockdown, reporter assays, Xenopus embryo gain/loss-of-function, splice isoform analysis Molecular and cellular biology High 17591701
2007 Erbin forms a specific complex with Cav1.3 (L-type) but not Cav1.2 Ca2+ channels via PDZ domain interaction with the C-terminus of the long variant of Cav1.3 α1 subunit; Erbin enhances voltage-dependent facilitation (VDF) of Cav1.3 currents by relieving autoinhibition imposed by the α1.3 C-terminal domain. Co-IP from brain lysates, co-localization in cortical neurons, electrophysiology (whole-cell patch clamp), domain deletion mutagenesis The Journal of neuroscience High 17287512
2008 Palmitoylation of ERBIN at cysteines 14 and 16 in its N-terminal region is required for its plasma membrane localization; mutants with C14S and/or C16S substitutions localize to the cytoplasm rather than the plasma membrane, and both palmitoylation and LRR domain are required for membrane targeting. Mutagenesis of palmitoylation sites, in vivo palmitoylation detection, localization studies in transfected cells Genes to cells High 18498353
2008 Erbin controls dendritic morphogenesis in hippocampal neurons by maintaining appropriate localization of delta-catenin; Erbin knockdown causes severe dendritic morphogenesis defects that are rescued by delta-catenin overexpression (but not vice versa), placing Erbin upstream of delta-catenin. shRNA knockdown, genetic knockout, rescue experiments, epistasis (Erbin upstream of delta-catenin), live imaging The Journal of neuroscience High 18614673
2009 Erbin is necessary for NRG1 signaling and PNS myelination; Erbin null mice display hypomyelination and reduced ErbB2 protein levels in sciatic nerves; Erbin with PDZ domain deletion (erbin ΔC/ΔC mice) phenocopies this, indicating that Erbin stabilizes ErbB2 protein via PDZ domain interaction. Erbin null mouse, erbin ΔC/ΔC knock-in mouse, electrophysiology, electron microscopy, protein level analysis, siRNA knockdown in cultured cells PNAS High 19458253
2009 Erbin controls the functional output of Merlin (NF2 tumor suppressor) by determining whether Merlin inhibits or is inhibited by active PAK2; in epithelial cells, Erbin/Merlin complexes bind and inactivate GTPase-bound PAK2, preventing TGF-β-induced PAK2 activation. Co-IP, siRNA knockdown, kinase activity assays, epistasis in epithelial vs. mesenchymal cells Developmental cell High 19289088
2011 ERBIN is a new SARA-interacting protein recruited by SARA to early endosomes; SARA binds ERBIN via an ERBID domain on SARA, and ERBIN binds SARA via a SSID domain (aa 1208-1265) that also interacts with SMAD2/3; SARA competes with SMAD2/3 for binding to ERBIN and overexpression of SARA or ERBID peptide reverses ERBIN's inhibitory effect on SMAD2/3-dependent transcription. Co-IP, domain mapping, competition assays, reporter assays, confocal microscopy Journal of cell science High 21878490
2012 Erbin is required for remyelination of regenerated axons after injury; Erbin expression increases dramatically in injured nerves; Erbin null mice show fewer myelinated axons, impaired functional recovery, and reduced ErbB2 and NRG1 levels in axons after nerve injury. Erbin null mouse with sciatic nerve crush, electron microscopy, electrophysiology, Western blot for ErbB2 and NRG1 The Journal of neuroscience High 23100438
2013 Erbin is specifically expressed in cortical inhibitory (PV-positive) interneurons, localizes at excitatory synapses, and regulates AMPA receptor (AMPAR) surface expression by interacting with and stabilizing TARP γ-2; deletion of the γ-2-interacting domain in Erbin attenuates surface AMPAR and excitatory transmission specifically in PV interneurons. Conditional mouse knockouts, electrophysiology (mEPSC recordings), Co-IP, protein stability assays, behavioral analysis Nature neuroscience High 23354328
2013 Desmoglein-1 (DSG1) promotes keratinocyte differentiation by binding Erbin (identified via yeast 2-hybrid screen); DSG1 requires Erbin to suppress ERK signaling; Erbin blocks ERK by interacting with and disrupting Ras-Raf scaffolds mediated by SHOC2; DSG1 overexpression enhances Erbin-SHOC2 interactions and decreases Ras-SHOC2 interactions. Yeast two-hybrid, Co-IP, siRNA knockdown, ERK activity assays, differentiation marker induction, patient biopsy analysis The Journal of clinical investigation High 23524970
2014 Erbin forms a complex with ErbB2 and HSP90, promoting ErbB2 stability by preventing its degradation; deletion of the Erbin PDZ domain hinders ErbB2-dependent tumor development in MMTV-neu mice; disruption of Erbin-ErbB2 interaction decreases ErbB2-dependent proliferation. Co-IP (Erbin-ErbB2-HSP90 complex), MMTV-neu mouse model with Erbin PDZ deletion (erbin ΔC/ΔC), proliferation assays PNAS High 25288731
2014 Erbin is a novel substrate of the SAG-βTrCP E3 ubiquitin ligase; SAG degrades Erbin to activate the Ras-Raf pathway; Erbin accumulation upon Sag deletion blocks Ras activation of Raf, and simultaneous one-allele deletion of Erbb2ip partially rescues SAG deletion phenotypes in keratinocytes. E3 ligase substrate identification, Co-IP, ubiquitination assay, Sag knockout mouse, Erbin genetic rescue The Journal of cell biology High 26056141
2015 Erbin inhibits EGFR ubiquitination and stabilizes EGFR by interacting with c-Cbl (an E3 ubiquitin ligase for EGFR); the PDZ domain of Erbin is critical for interaction with c-Cbl and EGFR ubiquitination; deletion of Erbin PDZ domain (ErbinΔC/ΔC mice) demonstrates this regulation is necessary for CRC tumorigenesis. Co-IP, ubiquitination assay, PDZ domain deletion mice (ErbinΔC/ΔC), AOM-induced colon carcinogenesis, xenograft model The Journal of pathology High 25521828
2017 ERBIN acts as a SMAD anchor for receptor activation (SARA) and SMAD2/3 binding protein; STAT3 negatively regulates TGF-β signaling via ERBIN by forming a STAT3-ERBIN-SMAD2/3 complex; loss-of-function ERBB2IP mutations impair STAT3-ERBIN-SMAD2/3 complex formation, fail to constrain nuclear pSMAD2/3, leading to increased IL-4Rα expression and enhanced Th2 responses. Co-IP of STAT3-ERBIN-SMAD2/3 complex, patient-derived cells with ERBB2IP loss-of-function mutation, in vitro reconstitution, nuclear fractionation The Journal of experimental medicine High 28126831
2017 Erbin inactivates ERα signaling in HCC by interacting with ERα and enhancing binding of CHIP (an E3 ligase) to ERα, thereby promoting ubiquitination and degradation of ERα; deletion of Erbin PDZ domain disrupts Erbin-CHIP-ERα interaction, stabilizes ERα protein. Co-IP, ubiquitination assay, ErbinΔC/ΔC mice, DEN-induced HCC model, cell proliferation assays Journal of hepatology High 28192186
2018 Erbin interacts with KSR1 and displaces it from the RAF/MEK/ERK complex to prevent signal propagation; genetic deletion of Erbin in Apc knockout mice promotes colorectal tumorigenesis and significantly reduces survival. Co-IP, siRNA knockdown, Erbin/Apc double knockout mice, 3D organoid cultures, gene set enrichment analysis Cancer research High 29980571
2019 Erbin in amygdala parvalbumin (PV)-positive neurons is critical for maintaining excitatory postsynaptic responses on PV neurons and for excitation-inhibition balance in the amygdala; Erbin knockout or PV-specific Erbin knockdown reduces excitatory postsynaptic responses on PV neurons and increases anxiety-like behaviors; chemogenetic activation of amygdala PV neurons rescues anxiety in Erbin knockdown mice. Conditional knockdown in amygdala PV neurons, electrophysiology, chemogenetics (DREADD), behavioral assays Biological psychiatry High 31889536
2019 Scribble, Erbin, and Lano (three LAP proteins) redundantly regulate epithelial apicobasal polarity; triple Scrib/Erbin/Lano knockout disorganizes cell junctions, cytoskeleton, and mislocalizes apical and basolateral identity proteins; the conserved LAPSDa domain of these proteins is essential for basolateral identity and Llgl binding. Triple knockout in epithelial cells, rescue with LAP protein domains, immunofluorescence, structure-function analysis The Journal of cell biology High 31147384
2010 Erbin interacts with MuSK and forms a complex with both MuSK and ErbB2 simultaneously; knockdown of Erbin reduces the density of agrin-dependent AChR aggregates on primary skeletal myotubes, demonstrating a role for Erbin at the NMJ in linking agrin and neuregulin signaling pathways. Co-IP, domain mapping of Erbin-MuSK interaction, siRNA knockdown, AChR aggregate density assay in primary myotubes The Journal of neuroscience High 20463225
2023 The C-terminal region of Erbin (aa 391-964) interacts with the N-terminal region of transcription factor EB (TFEB) (aa 1-247), affects TFEB-14-3-3 and TFEB-PPP3CB complex stability and TFEB phosphorylation status, thereby promoting nuclear translocation of TFEB and lysosome biogenesis to support autophagy. Co-IP with domain mapping, TFEB nuclear translocation assays, autophagy flux assays, sepsis mouse model Journal of translational medicine Medium 38105228
2024 Erbin-deficient platelets/megakaryocytes show increased mitochondrial oxidative phosphorylation and secrete lipid metabolites (acyl-carnitine) by abolishing interaction with the prothrombotic protein ESAM; acyl-carnitine then promotes B cell-mediated antitumor immunity. Platelet/MK-specific Erbin knockout mice, Co-IP (Erbin-ESAM interaction), metabolomics, mitochondrial function assays, in vivo metastasis models Cell metabolism High 38232736
2024 VCPIP1 is a deubiquitinase that interacts with Erbin and stabilizes it through deubiquitination; VCPIP1 deficiency reduces Erbin expression, increases NF-κB phosphorylation, and promotes release of inflammatory cytokines in macrophages. Deubiquitinase plasmid library screen, Co-IP, ubiquitination assay, siRNA knockdown, inflammatory cytokine measurement International immunopharmacology Medium 39550842
2024 NoxO1 interacts with Erbin (identified by BioID proximity labeling) and co-localizes with EGFR; NoxO1 overexpression delays EGF-mediated kinase activation while NoxO1 KO has the opposite effect, suggesting NoxO1 modulates EGFR signaling through interaction with Erbin. BioID proximity labeling, co-localization microscopy, EGFR signaling assays in NoxO1 KO and OE cells Redox biology Medium 39426288
2012 Erbin mediates catecholamine-induced β2-adrenergic receptor/Her2 complex formation via its PDZ domain (but not LRR domain); silencing of Erbin abrogates isoproterenol-induced ERK activation and causes severe cardiomyocyte apoptosis upon ISO treatment. Co-IP (β2-AR, Her2, Erbin complex), Erbin deletion mutants, siRNA knockdown, ERK activation assays, apoptosis assay in cardiomyocytes International journal of cardiology Medium 22564389
2014 Erbin expression is regulated by the transcription factor MITF; under basal conditions MITF activates Erbin expression via direct promoter binding; under β-adrenergic stimulation, FHL2 forms a complex with MITF (confirmed by Co-IP) and switches MITF from an activator to a repressor of Erbin promoter activity, contributing to cardiac hypertrophy. Yeast two-hybrid, Co-IP, chromatin immunoprecipitation (ChIP), promoter reporter assay, MITF mutant mice International journal of cardiology Medium 26025865
2013 Erbin interacts with Sema4C via Co-IP in HK2 renal tubular epithelial cells; overexpression of Erbin blocks Sema4C-induced epithelial-mesenchymal transition, and Erbin siRNA promotes EMT induced by Sema4C. Co-IP, Western blot for EMT markers, siRNA knockdown, overexpression Journal of Huazhong University Low 24142719

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 ERBIN: a basolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor. Nature cell biology 264 10878805
1999 LAP2 binding protein 1 (L2BP1/BAF) is a candidate mediator of LAP2-chromatin interaction. Journal of cell science 195 10393804
2001 Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA. The EMBO journal 187 11500367
2001 LAP2 binds to BAF.DNA complexes: requirement for the LEM domain and modulation by variable regions. The EMBO journal 179 11285238
1995 Cloning of a cDNA for lamina-associated polypeptide 2 (LAP2) and identification of regions that specify targeting to the nuclear envelope. The EMBO journal 167 7737115
2020 The circular RNA circ-ERBIN promotes growth and metastasis of colorectal cancer by miR-125a-5p and miR-138-5p/4EBP-1 mediated cap-independent HIF-1α translation. Molecular cancer 158 33225938
2005 A role for Erbin in the regulation of Nod2-dependent NF-kappaB signaling. The Journal of biological chemistry 156 16203728
2006 Role for erbin in bacterial activation of Nod2. Infection and immunity 133 16714539
1999 Roles of LAP2 proteins in nuclear assembly and DNA replication: truncated LAP2beta proteins alter lamina assembly, envelope formation, nuclear size, and DNA replication efficiency in Xenopus laevis extracts. The Journal of cell biology 133 10087255
2002 The Erbin PDZ domain binds with high affinity and specificity to the carboxyl termini of delta-catenin and ARVCF. The Journal of biological chemistry 130 11821434
2002 Origins of PDZ domain ligand specificity. Structure determination and mutagenesis of the Erbin PDZ domain. The Journal of biological chemistry 127 12446668
2013 Desmoglein-1/Erbin interaction suppresses ERK activation to support epidermal differentiation. The Journal of clinical investigation 115 23524970
2002 Erbin suppresses the MAP kinase pathway. The Journal of biological chemistry 103 12379659
1998 The major nuclear envelope targeting domain of LAP2 coincides with its lamin binding region but is distinct from its chromatin interaction domain. The Journal of biological chemistry 100 9461618
1997 Lamin-binding fragment of LAP2 inhibits increase in nuclear volume during the cell cycle and progression into S phase. The Journal of cell biology 98 9382857
2002 Novel mode of ligand recognition by the Erbin PDZ domain. The Journal of biological chemistry 91 12444095
2005 Erbin inhibits RAF activation by disrupting the sur-8-Ras-Raf complex. The Journal of biological chemistry 88 16301319
2001 Erbin is a protein concentrated at postsynaptic membranes that interacts with PSD-95. The Journal of biological chemistry 84 11279080
2001 Interaction between Erbin and a Catenin-related protein in epithelial cells. The Journal of biological chemistry 84 11711544
2001 The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins. The Journal of biological chemistry 82 11278603
2017 ERBIN deficiency links STAT3 and TGF-β pathway defects with atopy in humans. The Journal of experimental medicine 80 28126831
2001 The hemidesmosomal protein bullous pemphigoid antigen 1 and the integrin beta 4 subunit bind to ERBIN. Molecular cloning of multiple alternative splice variants of ERBIN and analysis of their tissue expression. The Journal of biological chemistry 69 11375975
2002 ERBIN associates with p0071, an armadillo protein, at cell-cell junctions of epithelial cells. Genes to cells : devoted to molecular & cellular mechanisms 67 12047349
2018 LncRNA KTN1-AS1 promotes tumor growth of hepatocellular carcinoma by targeting miR-23c/ERBB2IP axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 64 30551364
2009 Erbin regulates NRG1 signaling and myelination. Proceedings of the National Academy of Sciences of the United States of America 63 19458253
1998 Nuclear envelope remodelling during rat spermiogenesis: distribution and expression pattern of LAP2/thymopoietins. Journal of cell science 61 9664044
2003 HA95 and LAP2 beta mediate a novel chromatin-nuclear envelope interaction implicated in initiation of DNA replication. The Journal of cell biology 60 12538639
2005 Erbin regulates mitogen-activated protein (MAP) kinase activation and MAP kinase-dependent interactions between Merlin and adherens junction protein complexes in Schwann cells. The Journal of biological chemistry 59 15659388
2022 Erbin protects against sepsis-associated encephalopathy by attenuating microglia pyroptosis via IRE1α/Xbp1s-Ca2+ axis. Journal of neuroinflammation 58 36171629
2007 Erbin inhibits transforming growth factor beta signaling through a novel Smad-interacting domain. Molecular and cellular biology 56 17591701
2019 Erbin in Amygdala Parvalbumin-Positive Neurons Modulates Anxiety-like Behaviors. Biological psychiatry 53 31889536
2018 LAP2 Proteins Chaperone GLI1 Movement between the Lamina and Chromatin to Regulate Transcription. Cell 53 30503211
2013 Erbin interacts with TARP γ-2 for surface expression of AMPA receptors in cortical interneurons. Nature neuroscience 46 23354328
2019 Scribble, Erbin, and Lano redundantly regulate epithelial polarity and apical adhesion complex. The Journal of cell biology 45 31147384
2010 Loss of LAP2 alpha delays satellite cell differentiation and affects postnatal fiber-type determination. Stem cells (Dayton, Ohio) 43 20039368
2014 Role of Erbin in ErbB2-dependent breast tumor growth. Proceedings of the National Academy of Sciences of the United States of America 42 25288731
2007 Erbin enhances voltage-dependent facilitation of Ca(v)1.3 Ca2+ channels through relief of an autoinhibitory domain in the Ca(v)1.3 alpha1 subunit. The Journal of neuroscience : the official journal of the Society for Neuroscience 42 17287512
2009 Erbin and the NF2 tumor suppressor Merlin cooperatively regulate cell-type-specific activation of PAK2 by TGF-beta. Developmental cell 41 19289088
2015 Erbin interacts with c-Cbl and promotes tumourigenesis and tumour growth in colorectal cancer by preventing c-Cbl-mediated ubiquitination and down-regulation of EGFR. The Journal of pathology 40 25521828
2012 Erbin is required for myelination in regenerated axons after injury. The Journal of neuroscience : the official journal of the Society for Neuroscience 40 23100438
2008 Erbin controls dendritic morphogenesis by regulating localization of delta-catenin. The Journal of neuroscience : the official journal of the Society for Neuroscience 40 18614673
2002 Localization of p0071-interacting proteins, plakophilin-related armadillo-repeat protein-interacting protein (PAPIN) and ERBIN, in epithelial cells. Oncogene 40 12370826
2017 Elevated expression of Erbin destabilizes ERα protein and promotes tumorigenesis in hepatocellular carcinoma. Journal of hepatology 38 28192186
2002 Basolateral targeting of ERBB2 is dependent on a novel bipartite juxtamembrane sorting signal but independent of the C-terminal ERBIN-binding domain. Molecular and cellular biology 37 12192053
2018 miR-23c suppresses tumor growth of human hepatocellular carcinoma by attenuating ERBB2IP. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 34 30103114
2024 Targeting Erbin-mitochondria axis in platelets/megakaryocytes promotes B cell-mediated antitumor immunity. Cell metabolism 33 38232736
2015 Erbin is a novel substrate of the Sag-βTrCP E3 ligase that regulates KrasG12D-induced skin tumorigenesis. The Journal of cell biology 33 26056141
2018 Erbin exerts a protective effect against inflammatory bowel disease by suppressing autophagic cell death. Oncotarget 30 29552291
2003 The lamina-associated polypeptide 2 (LAP2) isoforms beta, gamma and omega of zebrafish: developmental expression and behavior during the cell cycle. Journal of cell science 30 12734396
2013 Deficiency of Erbin induces resistance of cervical cancer cells to anoikis in a STAT3-dependent manner. Oncogenesis 29 23774064
2011 Erbin inhibits TGF-β1-induced EMT in renal tubular epithelial cells through an ERK-dependent pathway. Journal of molecular medicine (Berlin, Germany) 29 22116522
2014 Erbin is a negative modulator of cardiac hypertrophy. Proceedings of the National Academy of Sciences of the United States of America 28 24711380
2003 Erbin: sorting out ErbB2 receptors or giving Ras a break? Science's STKE : signal transduction knowledge environment 27 12966186
2018 Erbin Suppresses KSR1-Mediated RAS/RAF Signaling and Tumorigenesis in Colorectal Cancer. Cancer research 26 29980571
2012 LAP2 is widely overexpressed in diverse digestive tract cancers and regulates motility of cancer cells. PloS one 26 22745766
2010 Erbin, a negative regulator in diverse signal pathways. Current protein & peptide science 26 21235511
2019 miR-183-5p Inhibits Occurrence and Progression of Acute Myeloid Leukemia via Targeting Erbin. Molecular therapy : the journal of the American Society of Gene Therapy 25 30799283
2011 ERBIN is a new SARA-interacting protein: competition between SARA and SMAD2 and SMAD3 for binding to ERBIN. Journal of cell science 25 21878490
2021 Mutual Promotion of LAP2 and CAT2 Synergistically Regulates Plant Salt and Osmotic Stress Tolerance. Frontiers in plant science 24 34177987
2005 Comparative analysis of the expression of ERBIN and Erb-B2 in normal human skin and cutaneous carcinomas. The British journal of dermatology 24 15948989
2019 Desmoglein 1 Regulates Invadopodia by Suppressing EGFR/Erk Signaling in an Erbin-Dependent Manner. Molecular cancer research : MCR 23 30655320
2021 Targeting Erbin in B cells for therapy of lung metastasis of colorectal cancer. Signal transduction and targeted therapy 22 33707428
2013 Differential expression of neuregulin-1 isoforms and downregulation of erbin are associated with Erb B2 receptor activation in diabetic peripheral neuropathy. Acta neuropathologica communications 22 24252174
2012 β2-AR-induced Her2 transactivation mediated by Erbin confers protection from apoptosis in cardiomyocytes. International journal of cardiology 21 22564389
2013 Downregulation of Erbin in Her2-overexpressing breast cancer cells promotes cell migration and induces trastuzumab resistance. Molecular immunology 20 23711387
2011 The Arabidopsis aminopeptidase LAP2 regulates plant growth, leaf longevity and stress response. The New phytologist 20 21569035
2007 Enhanced expression of the nuclear envelope LAP2 transcriptional repressors in normal and malignant activated lymphocytes. Annals of hematology 20 17364180
2018 Nuclear lamina genetic variants, including a truncated LAP2, in twins and siblings with nonalcoholic fatty liver disease. Hepatology (Baltimore, Md.) 19 28902428
2010 Identification of Erbin interlinking MuSK and ErbB2 and its impact on acetylcholine receptor aggregation at the neuromuscular junction. The Journal of neuroscience : the official journal of the Society for Neuroscience 19 20463225
2015 Erbin loss promotes cancer cell proliferation through feedback activation of Akt-Skp2-p27 signaling. Biochemical and biophysical research communications 18 26025650
1996 Expression of thymopoietin beta/lamina-associated polypeptide 2 (TP beta/LAP2) and its family proteins as revealed by specific antibody induced against recombinant human thymopoietin. Biochemical and biophysical research communications 17 8806652
2014 Alteration of the C-terminal ligand specificity of the erbin PDZ domain by allosteric mutational effects. Journal of molecular biology 16 24813123
2008 Palmitoylation of ERBIN is required for its plasma membrane localization. Genes to cells : devoted to molecular & cellular mechanisms 16 18498353
2024 circ-Erbb2ip from adipose-derived mesenchymal stem cell-derived exosomes promotes wound healing in diabetic mice by inducing the miR-670-5p/Nrf1 axis. Cellular signalling 15 38849105
2008 Erbin-regulated sensitivity of MCF-7 breast cancer cells to TRAIL via ErbB2/AKT/NF-kappaB pathway. Journal of biochemistry 15 18316330
2023 Erbin accelerates TFEB-mediated lysosome biogenesis and autophagy and alleviates sepsis-induced inflammatory responses and organ injuries. Journal of translational medicine 14 38105228
2014 Transcriptional regulation of miR-146b by C/EBPβ LAP2 in esophageal cancer cells. Biochemical and biophysical research communications 14 24589738
2015 FHL2 switches MITF from activator to repressor of Erbin expression during cardiac hypertrophy. International journal of cardiology 13 26025865
2008 The PDZ protein erbin modulates beta-catenin-dependent transcription. European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes 13 18667832
2023 Exosomal ERBB2IP contributes to tumor growth via elevating PSAT1 expression in non-small cell lung carcinoma. Thoracic cancer 11 37192746
2011 Prolonged regulatable expression of EPO from an HSV vector using the LAP2 promoter element. Gene therapy 11 22089494
2013 Erbin interacts with Sema4C and inhibits Sema4C-induced epithelial-mesenchymal transition in HK2 cells. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 9 24142719
2002 Lamina-associated polypeptide 2 (LAP2) expression in fish and amphibians. The International journal of developmental biology 9 11934151
2024 Erbin alleviates sepsis-induced cardiomyopathy by inhibiting RIPK1-dependent necroptosis through activating PKA/CREB pathway. Cellular signalling 8 39216682
2008 Biochemical studies and molecular dynamics simulations of Smad3-Erbin interaction identify a non-classical Erbin PDZ binding. Biochemical and biophysical research communications 8 19013433
2023 Knockout of Erbin promotes pyroptosis via regulating NLRP3/caspase-1/Gasdermin D pathway in sepsis-induced acute kidney injury. Clinical and experimental nephrology 7 37310569
2023 ERBIN and phosphoglucomutase 3 deficiency. Current opinion in immunology 6 37369151
2020 Reduced IκBα promotes hepatocellular carcinoma cell proliferation and migration via regulation of NF-κB/Erbin axis. Oncology letters 6 32963622
2019 Therapeutic effects of Erbin inhibitor on spinal cord contusion in mice. American journal of translational research 6 31105863
2018 Erbin plays a critical role in human umbilical vein endothelial cell migration and tubular structure formation via the Smad1/5 pathway. Journal of cellular biochemistry 6 30367512
2012 c-Myb regulates cell cycle-dependent expression of Erbin: an implication for a novel function of Erbin. PloS one 6 22880131
2023 Abnormal Cellular Phenotypes Induced by Three TMPO/LAP2 Variants Identified in Men with Cardiomyopathies. Cells 5 36672271
2022 Circular RNA ERBIN Promotes Proliferation of Hepatocellular Carcinoma via the miR-1263/CDK6 Axis. Frontiers in oncology 5 35530358
2017 Erbin and ErbB2 play roles in the sexual differentiation of the song system nucleus HVC in bengalese finches (Lonchura Striata var. domestica). Developmental neurobiology 5 29082632
2015 ERBB2 oncogenicity: ERBIN helps to perform the job. Molecular & cellular oncology 5 27308480
2017 The Role of Erbin in GTS-21 Regulating Inflammtory Responses in MDP-Stimulated Macrophages. Shock (Augusta, Ga.) 4 28410331
2008 Overexpression, refolding, purification of Erbin PDZ domain from Escherichia coli and preparation of its polyclonal antibody. Preparative biochemistry & biotechnology 4 18569875
2004 The lamina-associated polypeptide 2 (LAP2) genes of zebrafish and chicken: no LAP2alpha isoform is synthesised by non-mammalian vertebrates. European journal of cell biology 4 15506564
2024 NoxO1 regulates EGFR signaling by its interaction with Erbin. Redox biology 3 39426288
2024 VCPIP1 negatively regulates NF-κB signaling pathways by deubiquitinating and stabilizing Erbin in MDP-stimulated macrophages. International immunopharmacology 3 39550842