Affinage

NHERF2

Na(+)/H(+) exchange regulatory cofactor NHE-RF2 · UniProt Q15599

Length
337 aa
Mass
37.4 kDa
Annotated
2026-06-10
75 papers in source corpus 50 papers cited in narrative 50 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NHERF2 (E3KARP) is a dual-PDZ-domain apical scaffold that organizes macromolecular signaling complexes in polarized epithelia, coupling membrane transporters and receptors to regulatory kinases and to the actin cytoskeleton (PMID:9748260, PMID:9792717, PMID:21430287). Its second PDZ domain binds the C-terminal PDZ motifs of the Na+/H+ exchanger NHE3, CFTR, the Cl-/HCO3- exchanger DRA, the LPA2 receptor, P2Y1R, mGluR5, and other transporters with high affinity, while a C-terminal ERM-binding domain engages ezrin to tether these complexes near the apical actin cortex (PMID:9748260, PMID:9792717, PMID:10893422, PMID:12369822, PMID:15143197, PMID:15901899, PMID:24613836). Through this platform NHERF2 specifically (and distinctly from NHERF1) localizes second-messenger machinery to NHE3: it anchors PKA-, cGMP-dependent protein kinase II (cGKII), Ca2+/PKCalpha, and CaMKII signaling for NHE3 inhibition, and SGK1 for stimulation of NHE3 and other transporters including ROMK1, PEPT2, and TRPV5 (PMID:9748260, PMID:9792717, PMID:11751930, PMID:12954600, PMID:15722341, PMID:22371496, PMID:15665527, PMID:19088452, PMID:12444200). NHERF2 also controls receptor output by determining G-protein coupling and effector specificity, linking LPA2 to PLCbeta3/ERK/COX-2 signaling and restricting P2Y1R/mGluR5 coupling to CaV2.2 channels (PMID:15143197, PMID:21134377, PMID:20720114). Knockout mouse studies establish that NHERF2 is required in intestine for basal NHE3 apical localization and for cGMP-, Ca2+-, and LPA-mediated regulation of NHE3 and CFTR-dependent secretion, tethering NHE3 near the terminal web and within brush-border lipid rafts (PMID:19221439, PMID:19800338, PMID:20962002, PMID:21430287, PMID:38533975). The interaction is dynamic: elevated Ca2+ or LPA stimulation (via an ERK-PLC-PKCdelta module) transiently dissociates the NHERF2-NHE3 complex to increase exchanger mobility, and phosphorylation of Ser303 in NHERF2's unique C-terminal ERM-binding regulatory sequence by A-Raf during mitosis reduces ezrin binding and releases NHERF2 into the cytosol (PMID:21799002, PMID:24760985, PMID:26251448, PMID:26310448). Beyond epithelial transport, NHERF2 acts as a negative regulator of endothelial proliferation and is targeted for degradation by HPV E6 oncoproteins, linking its loss to p27/cyclin D1 dysregulation (PMID:22343917, PMID:31597772).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1998 High

    Established the founding scaffold model: how cAMP-dependent regulation of NHE3 is spatially organized, by showing NHERF2 physically links NHE3 to ezrin and PKA.

    Evidence In vitro binding with domain mapping and co-IP in fibroblasts/opossum kidney cells, with NHE3 activity assays

    PMID:9748260 PMID:9792717

    Open questions at the time
    • Did not establish whether NHERF2 vs NHERF1 confer distinct selectivity
    • Direct demonstration of PKA tethering in native epithelium absent
  2. 1998 Medium

    Defined NHERF2 as a passive adapter rather than a kinase substrate, clarifying that its regulatory role is structural localization of PKA.

    Evidence In vivo phosphorylation studies and co-IP in opossum kidney cells

    PMID:9792717

    Open questions at the time
    • Did not exclude regulatory phosphorylation by other kinases (later shown at Ser303)
  3. 2000 High

    Extended the scaffold to CFTR, showing NHERF2 functionally potentiates cAMP-stimulated Cl- currents via PDZ2 and ezrin.

    Evidence Nanomolar binding assays, co-IP, and Xenopus oocyte electrophysiology

    PMID:10893422

    Open questions at the time
    • Physiological context of CFTR regulation not yet tested in epithelium
  4. 2001 High

    Identified NHERF2 as the specific scaffold (vs NHERF1) coupling the kinase SGK1 to NHE3, explaining glucocorticoid activation of the exchanger.

    Evidence Co-expression with dominant-negative kinase-dead SGK1 and NHE3 activity assays in two cell lines

    PMID:11751930

    Open questions at the time
    • Direct SGK1 phosphorylation site on NHE3 or NHERF2 not mapped here
  5. 2001 Medium

    Showed NHERF2 self- and hetero-oligomerizes via PDZ domains, indicating scaffolds can multimerize to assemble larger complexes.

    Evidence Purified PDZ domain association assays and co-IP with tagged constructs

    PMID:11456497

    Open questions at the time
    • Functional consequence of oligomerization on transporter regulation not established
    • Stoichiometry in vivo unknown
  6. 2002 High

    Resolved the mechanism of Ca2+-dependent NHE3 inhibition: NHERF2 specifically recruits alpha-actinin-4 and PKCalpha to drive NHE3 oligomerization and endocytosis.

    Evidence Stable transfection, NHE3 activity, co-IP, dominant-negative, and surface biotinylation in PS120 cells

    PMID:11948184 PMID:12954600

    Open questions at the time
    • Whether oligomerization precedes or follows endocytosis not fully ordered
    • alpha-actinin-4 recruitment trigger details incomplete
  7. 2002 Medium

    Broadened the apical interactome to include the DRA Cl-/HCO3- exchanger and adenosine A2b receptor, supporting NHERF2 as a coordinator of parallel transport/receptor systems.

    Evidence In vitro PDZ binding with GST fusions and agonist-dependent co-IP in intestinal epithelial cell lines

    PMID:12080047 PMID:12369822

    Open questions at the time
    • Functional coupling of DRA and NHE3 via NHERF2 not demonstrated physiologically
    • A2bR interaction context limited to co-IP
  8. 2004 High

    Demonstrated NHERF2 dictates receptor signaling output by linking LPA2 to PLCbeta3, forming a ternary complex driving ERK/COX-2 signaling.

    Evidence Co-IP, PDZ mutants, siRNA knockdown, and inositol phosphate assays with isoform selectivity

    PMID:15143197 PMID:15238220

    Open questions at the time
    • In vivo relevance not yet established (addressed later by knockouts)
  9. 2005 High

    Established NHERF2 as a protein kinase G anchoring protein, identifying it as required for cGMP (cGKII)-mediated NHE3 inhibition distinct from NHERF1.

    Evidence Co-expression, in vitro cGKII binding, non-myristoylated mutant, and NHE3 activity assays

    PMID:15722341

    Open questions at the time
    • Structural basis of cGKII recognition not resolved
  10. 2005 High

    Generalized the receptor-tethering function to neuronal/glial GPCRs (P2Y1R, mGluR5) and to apical polarity (podocalyxin), prolonging Ca2+ signaling and shaping epithelial organization.

    Evidence PDZ array screens, co-IP, point-mutant functional Ca2+ assays, and RNAi polarization phenotypes

    PMID:15642748 PMID:15901899 PMID:16891310

    Open questions at the time
    • Mechanism by which NHERF2 prolongs Ca2+ signals (effector retention vs recycling) not fully resolved
  11. 2008 Medium

    Expanded the SGK1/NHERF2 module to multiple transporters (ROMK1, TRPV5, PEPT2), showing NHERF2 stabilizes surface abundance by limiting endocytosis.

    Evidence Xenopus oocyte electrophysiology, surface abundance assays, and dynasore endocytosis block

    PMID:12444200 PMID:15665527 PMID:19088452

    Open questions at the time
    • Native-tissue relevance for these transporters not demonstrated
    • Direct SGK1 phosphosites variably mapped
  12. 2009 High

    Provided in vivo genetic proof that NHERF2 couples LPA receptors (LPA5, not LPA2) to NHE3 stimulation and to inhibitory LPA-CFTR signaling in intestine.

    Evidence Nherf2-/- and Lpa2-/- mice with duodenal HCO3- secretion and intestinal fluid absorption measurements

    PMID:19221439 PMID:19800338

    Open questions at the time
    • Reconciliation of LPA2 (in vitro) vs LPA5 (in vivo) receptor usage incompletely resolved
  13. 2010 High

    Showed NHERF2 determines LPA2 G-protein coupling specificity by competing with MAGI-3, controlling migration vs NF-kappaB outcomes.

    Evidence Competitive binding, co-IP, and migration/invasion/IP/NF-kappaB assays in colorectal cells

    PMID:21134377

    Open questions at the time
    • Quantitative stoichiometry of the NHERF2/MAGI-3 competition in vivo unknown
  14. 2010 High

    Revealed the NHERF2-NHE3 interaction is dynamic, with LPA and Ca2+ transiently dissociating the complex to mobilize NHE3 via PI3K-dependent exocytosis.

    Evidence FRAP, acceptor-photobleaching FRET, co-IP, and PI3K inhibitor experiments in OK cells

    PMID:20571054 PMID:21799002

    Open questions at the time
    • Molecular trigger for reassociation at 60 min not identified
  15. 2010 High

    Established NHERF2 as the ezrin-dependent apical anchor for additional targets (PMCA2w/b, GLAST, TRPC4) and as a determinant of receptor-to-channel coupling in neurons.

    Evidence Surface biotinylation, FRAP, actin disruption, pulse-chase stability, native co-IP, and neuronal electrophysiology

    PMID:15590898 PMID:20430067 PMID:20663896 PMID:20720114

    Open questions at the time
    • Whether ezrin tethering is required for all of these targets uniformly not established
  16. 2010 Medium

    Identified NHERF2 as a negative regulator of endothelial proliferation, linking its loss to elevated Ca2+, c-Myc/cyclin D1, and reduced p27.

    Evidence siRNA knockdown, proliferation/cell-cycle analysis, and mouse hemangioma model

    PMID:22343917

    Open questions at the time
    • Mechanism connecting scaffold loss to cell-cycle gene changes not fully defined
  17. 2011 High

    Genetically confirmed NHERF2 is essential for basal NHE3 apical localization and for cAMP/cGMP/Ca2+ regulation across intestinal segments, with selective preservation of hyperosmolar inhibition.

    Evidence NHERF2-null mice with two-photon microscopy NHE3 activity and immunofluorescence

    PMID:20962002 PMID:21430287

    Open questions at the time
    • Redundancy with NHERF3 not yet dissected here
  18. 2012 High

    Added CaMKII and megalin-ClC-5 to the NHERF2-organized network, showing roles in basal NHE3 inhibition and proximal tubule receptor complex assembly.

    Evidence Phosphorylation/back-phosphorylation assays, domain-mapping co-IP, GST pulldown, and siRNA in tissue/cell models

    PMID:22349218 PMID:22371496

    Open questions at the time
    • CaMKII NHE3 phosphosite location only partially mapped
    • Functional output of megalin-ClC-5 scaffolding in vivo not measured
  19. 2013 High

    Localized NHERF2's distinctive slow microvillar mobility and base-of-microvillus positioning to its unique C-terminal tail, which is required for LPA stimulation and Ca2+ inhibition of NHE3.

    Evidence FRAP with NHERF1/2 chimeras and point mutants, functional NHE3 assays

    PMID:23612977 PMID:23985317

    Open questions at the time
    • Molecular partners conferring slow exchange not all identified
  20. 2013 Medium

    Linked NHERF2 to ERM/ROCK2 signaling in endothelium, establishing a role in agonist-induced ERM phosphorylation and cell attachment.

    Evidence Co-IP, siRNA, ERM-binding mutant, and ECIS/Matrigel functional assays

    PMID:24364877

    Open questions at the time
    • Direct ROCK2-NHERF2 binding interface not mapped
  21. 2014 High

    Defined the LPA-stimulated NHE3 mobilization pathway as an ERK-PLC-PKCdelta module that reversibly releases NHE3 from NHERF2, and identified a nuclear coactivator role for NHERF2 with ERalpha.

    Evidence FRAP, co-IP, PKCdelta knockdown, inhibitor ordering in OK cells; co-IP/ChIP/reporter assays in MCF7

    PMID:24613836 PMID:24760985 PMID:24771346

    Open questions at the time
    • How a predominantly apical scaffold accesses the nucleus for ERalpha coactivation not reconciled
  22. 2015 High

    Identified the Ser303-containing ERM-binding regulatory sequence (EBRS) as the master switch: its phosphorylation by A-Raf during mitosis reduces ezrin binding, relocates NHERF2 to cytosol, and disables SGK1/dexamethasone stimulation of NHE3.

    Evidence EBRS/phosphomimetic mutants, FRAP, ezrin co-IP, A-Raf RNAi, and NHE3/microvillus functional assays

    PMID:26251448 PMID:26310448

    Open questions at the time
    • Phosphatase reversing Ser303 not identified
    • Signals controlling A-Raf activity toward NHERF2 outside mitosis unknown
  23. 2017 High

    Defined functional redundancy and division of labor between NHERF2 and NHERF3 in intestinal NHE3 regulation, with NHERF2 uniquely required for glucose-stimulated activity.

    Evidence NHERF2 and NHERF3 knockout mice with two-photon NHE3 activity; mast cell shRNA functional assays

    PMID:23284683 PMID:24867958 PMID:28882822

    Open questions at the time
    • Mechanistic basis of NHERF2-specific glucose response not defined
    • C3aR functional effects occur without direct NHERF2 association
  24. 2019 High

    Connected NHERF2 loss to oncogenesis, showing HPV E6 targets it for proteasomal degradation to deregulate p27/cyclin D1, and later that NHERF2 stabilizes IkappaB to restrain NF-kappaB.

    Evidence Co-IP, E6 PBM mutants, proteasome inhibitor rescue, ubiquitination and NF-kappaB reporter assays in cancer cells

    PMID:31597772 PMID:37573425

    Open questions at the time
    • NHERF2-IkappaB stabilization confirmed in a single study/system
    • Whether E6-driven degradation operates in primary tumors not established
  25. 2024 High

    Placed the NHE3-NHERF2-cGKII complex in brush-border lipid rafts and showed NHERF2 is required for NHE3 raft association and guanylyl-cyclase-C-triggered redistribution.

    Evidence Density-gradient raft fractionation with NHE3, cGKII, and NHERF2 knockout mice and confocal imaging

    PMID:38533975

    Open questions at the time
    • Lipid determinants recruiting NHERF2 to rafts not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NHERF2's apical transport-scaffolding function mechanistically relates to its nuclear (ERalpha, SRY) and tumor-suppressive (IkappaB, p27) roles, and what governs target selection among its many PDZ ligands in a single cell, remains unresolved.
  • No unified model linking membrane scaffold vs nuclear functions
  • Determinants of competitive ligand selection among co-expressed PDZ partners unknown
  • Structural basis for PDZ2 promiscuity vs PDZ1 selectivity only partially defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 5 GO:0008092 cytoskeletal protein binding 3 GO:0140110 transcription regulator activity 1
Localization
GO:0005856 cytoskeleton 5 GO:0005886 plasma membrane 5 GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-382551 Transport of small molecules 5 R-HSA-9609507 Protein localization 4 R-HSA-1643685 Disease 2
Partners
CFTREZRGRM5LPAR2NHE3P2RY1PRKG2SGK1
Complex memberships
LPA2-NHERF2-PLCbeta3 ternary complexNHE3-NHERF2-ezrin scaffoldNHERF2-SCHIP1-ezrin complexmegalin-NHERF2-ClC-5 complex

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 NHERF2 (E3KARP) directly binds NHE3 via its second PDZ domain (plus C-terminal domain), and also binds the cytoskeletal protein ezrin via its C-terminal domain, forming a scaffold that localizes PKA near NHE3 to enable cAMP-dependent inhibition of NHE3. In vitro binding assays, co-localization in PS120 fibroblasts The Journal of biological chemistry High 9748260 9792717
1998 NHERF2 (E3KARP) is not phosphorylated by cAMP/PKA and does not change phosphorylation state upon 8-bromo-cAMP treatment; it functions as an adapter (not a direct PKA substrate) linking NHE3 to ezrin to localize PKA type II near NHE3. In vivo phosphorylation studies, co-immunoprecipitation in opossum kidney cells The Journal of biological chemistry Medium 9792717
2000 NHERF2 (E3KARP) associates with CFTR preferentially through CFTR's PDZ-binding motif and E3KARP's second PDZ domain with nanomolar affinity; E3KARP also associates with ezrin in vivo, and co-expression of CFTR with E3KARP and ezrin in Xenopus oocytes potentiates cAMP-stimulated CFTR Cl⁻ currents. Co-immunoprecipitation, confocal microscopy, cell fractionation, Xenopus oocyte electrophysiology The Journal of biological chemistry High 10893422
2001 SGK1 specifically interacts with PDZ domains of NHERF2 (but not NHERF1) to mediate glucocorticoid/dexamethasone activation of NHE3; kinase-dead SGK1 blocked NHE3 activation, demonstrating NHERF2 acts as a scaffold linking SGK1 to NHE3. Co-expression in PS120 fibroblasts and opossum kidney cells, dominant-negative kinase-dead SGK1, NHE3 activity assays The Journal of biological chemistry High 11751930
2001 NHERF-2 PDZ domains robustly self-associate (homo-oligomerize) without requiring additional proteins, and NHERF-1 and NHERF-2 form hetero-oligomers in cells via their PDZ domains; NHERF-2 oligomerization is not regulated by phosphorylation (unlike NHERF-1). Purified PDZ domain association assays, co-immunoprecipitation with differentially tagged constructs Biochemistry Medium 11456497
2002 Ca²⁺-dependent inhibition of NHE3 requires E3KARP (NHERF2) specifically (not NHERF1), and occurs via Ca²⁺-dependent association of alpha-actinin-4 with E3KARP through alpha-actinin-4's actin-binding domain plus spectrin repeat domain, leading to NHE3 oligomerization and endocytosis. Stable transfection of PS120 fibroblasts, NHE3 activity assays, co-immunoprecipitation, dominant-negative overexpression, surface biotinylation The Journal of biological chemistry High 11948184
2002 NHERF2 (E3KARP) binds the DRA (downregulated in adenoma) Cl⁻/HCO₃⁻ exchanger's C-terminal ETKF motif via the second PDZ domain, potentially linking parallel NHE3 and DRA transporters in the apical membrane. In vitro PDZ binding assays with GST fusion proteins, immunofluorescence co-localization in human proximal colon Biochemistry Medium 12369822
2002 Adenosine A2b receptor co-immunoprecipitates with E3KARP (NHERF2) and ezrin upon agonist stimulation; the A2bR is recruited to the plasma membrane and caveolar fractions upon agonist stimulation in intestinal epithelial cells. Co-immunoprecipitation from T84 and Caco2-BBE cells, confocal microscopy The Journal of biological chemistry Medium 12080047
2002 NHERF2 and SGK1 synergize to increase ROMK1 K⁺ channel activity by enhancing channel abundance in the plasma membrane; neither NHERF2 nor SGK1 alone affects ROMK1, but their combination markedly increases K⁺ channel activity and slows decay after brefeldin inhibition. Xenopus oocyte co-expression, electrophysiology, brefeldin A experiments Journal of the American Society of Nephrology Medium 12444200
2003 PKCα binds specifically to the PDZ1 domain of E3KARP (NHERF2) in a Ca²⁺-dependent manner; PKCα is necessary for Ca²⁺-dependent decrease in plasma membrane NHE3 (endocytosis) but not for NHE3 oligomerization. GST pulldown, co-immunoprecipitation, PKC inhibitors, surface biotinylation in PS120/NHE3/E3KARP cells American journal of physiology. Cell physiology High 12954600
2004 LPA receptor LPA2 (but not other LPA receptors) specifically interacts with NHERF2 via LPA2's C-terminal PDZ-binding motif and NHERF2's second PDZ domain; NHERF2 indirectly links LPA2 to PLC-β3 forming a ternary complex that specifically activates PLC-β3 and downstream ERK/COX-2 signaling. Co-immunoprecipitation, PDZ domain binding assays, siRNA knockdown of NHERF2 and PLC-β3, stable NHERF2 expression, inositol phosphate assay Molecular and cellular biology High 15143197
2004 NHERF2 (E3KARP) mediates LPA-induced stimulation of NHE3 by enabling LPA-induced PLC activation and subsequent intracellular Ca²⁺ elevation, which drives exocytic trafficking of NHE3 to the apical membrane in a PKC-independent manner. PLC inhibitor (U73122), Ca²⁺ chelator (BAPTA-AM), PKC inhibitor, NHE3 activity and surface amount in OK cells stably expressing E3KARP Biochimica et biophysica acta Medium 15238220
2004 NHERF2 co-immunoprecipitates with TRPC4 (but not TRPC5) from renal medullary lysates and they co-localize in descending vasa recta endothelial cells and pericytes. RT-PCR, immunohistochemistry, reciprocal co-immunoprecipitation from renal medullary lysates American journal of physiology. Cell physiology Medium 15590898
2005 NHERF2 is required for cGMP inhibition of NHE3 (while NHERF1 is not); NHERF2 acts as a novel protein kinase G-anchoring protein, binding cGKII via its PDZ2 C-terminus, and membrane myristoylation of cGKII is additionally required for NHE3 inhibition. Co-expression in PS120 cells, in vitro NHERF2-cGKII binding, non-myristoylated cGKII mutant, NHE3 activity assays The Journal of biological chemistry High 15722341
2005 NHERF-2 specifically interacts with the P2Y1 receptor C-terminus via NHERF-2's second PDZ domain; this interaction tethers P2Y1R to PLC-β and prolongs P2Y1R-mediated Ca²⁺ signaling in glial cells; point mutations disrupting the P2Y1R-NHERF-2 interaction attenuate the duration of Ca²⁺ responses. PDZ domain proteomic array screen, co-immunoprecipitation, confocal microscopy, functional Ca²⁺ signaling assays with point mutants Proceedings of the National Academy of Sciences of the United States of America High 15901899
2005 Podocalyxin (gp135) and NHERF-2 co-localize at a preapical subdomain in single MDCK cells and in terminally polarized apical membranes; the PDZ-binding motif of podocalyxin is required for this apical targeting, and depleting podocalyxin by RNAi causes defects in epithelial polarization. Domain deletion mutants, RNA interference of podocalyxin, confocal microscopy in MDCK cells The Journal of cell biology Medium 15642748
2005 NHERF2's second PDZ domain is required for SGK1/NHERF2-mediated stabilization of TRPV5 at the plasma membrane; the TRPV5 C-tail interacts with NHERF2 in a Ca²⁺-independent manner. Pull-down assays, PDZ domain deletion mutants, chemiluminescence surface abundance assay, Xenopus oocyte electrophysiology Cellular physiology and biochemistry Medium 15665527
2005 SIP-1/NHERF2 interacts with mouse SRY via the PDZ1 domain (involving an internal SRY domain rather than C-terminus as in human SRY), and both mouse and human SRY induce nuclear accumulation of NHERF2 in cultured cells; NHERF2 and SRY are co-expressed in the nucleus of pre-Sertoli cells during testis determination. Co-immunoprecipitation/interaction assays, nuclear accumulation assays in cultured cells, GFP-Sry transgenic mice for co-expression analysis The Journal of biological chemistry Medium 16166090
2006 NHERF-2 specifically interacts with mGluR5 (not mGluR1a) via NHERF-2's second PDZ domain; co-expression prolongs mGluR5-mediated Ca²⁺ mobilization and potentiates mGluR5-mediated cell death; a single point mutation in mGluR5-CT abolishes the interaction and attenuates these effects. PDZ domain proteomic array, co-immunoprecipitation, confocal microscopy, functional Ca²⁺ signaling assays with point mutants, cell death assays The Journal of biological chemistry High 16891310
2006 When NHE3 is co-expressed with CFTR, NHE3 sequesters NHERF2's PDZ2 domain, which prevents PDZ2 from participating in PKA-dependent apical CFTR expression and activation; deletion of NHERF2 binding domains inhibits PKA-dependent apical CFTR expression. NHERF2 PDZ domain deletion constructs, functional CFTR activity assays in A6-NHE3 cell monolayers Biochemical and biophysical research communications Medium 16824484
2008 NHERF2 (but not NHERF1) specifically enhances PEPT2 function and surface abundance via the PEPT2 C-terminal PDZ-binding motif; NHERF2 stabilizes PEPT2 at the cell surface (demonstrated by dynasore experiments) and acts together with SGK1 which phosphorylates PEPT2 at Ser185. Xenopus oocyte electrophysiology, surface abundance immunoassay, C-terminal deletion mutant, dynasore endocytosis inhibition Cellular physiology and biochemistry Medium 19088452
2009 NHERF2 confers inhibitory LPA receptor signaling to CFTR in duodenum; in Nherf2⁻/⁻ mice, FSK-stimulated HCO₃⁻ secretion is augmented, and LPA-mediated inhibition of CFTR-dependent secretion is abolished, demonstrating NHERF2 couples the LPA receptor to CFTR to provide inhibitory signals. Nherf2 knockout mouse model, duodenal HCO₃⁻ secretion measurements, laser microdissection and quantitative PCR The Journal of clinical investigation High 19221439
2009 LPA stimulates NHE3 and intestinal fluid absorption via the LPA5 receptor, and this stimulation requires NHERF2 which interacts with LPA5; LPA-mediated intestinal fluid absorption is absent in Nherf2⁻/⁻ mice but preserved in Lpa2⁻/⁻ mice; LPA increases NHE3 protein abundance at the brush border. Nherf2⁻/⁻ and Lpa2⁻/⁻ knockout mice, intestinal fluid absorption measurements, heterologous expression of LPA5 with NHERF2 Gastroenterology High 19800338
2010 NHERF2 silencing in endothelial cells causes hyperproliferation even without mitogens, associated with increased cytoplasmic calcium, increased c-Myc and cyclin D1, and reduced p27; NHERF2 is thus a negative regulator of endothelial proliferation. siRNA knockdown, cell proliferation assays, cell cycle analysis, mouse hemangioma model Blood Medium 22343917
2010 MAGI-3 competes with NHERF-2 for binding to LPA2 and PLC-β3; NHERF-2 promotes LPA2-Gαq coupling and stimulates PLC activity and cell migration, while MAGI-3 promotes LPA2-Gα12 coupling and inhibits NF-κB/JNK signaling, demonstrating NHERF-2 determines G-protein coupling specificity of LPA2. Overexpression and knockdown of MAGI-3 in HCT116/SW480 cells, co-immunoprecipitation, migration/invasion assays, inositol phosphate and NF-κB assays Gastroenterology High 21134377
2010 NHERF2 binding to NHE3 in brush borders is dynamic; LPA stimulation transiently dissociates the NHERF2-NHE3 complex (loss of co-precipitation and FRET signal at 30 min, re-established at 50-60 min), increasing NHE3 mobility via a PI3K-dependent exocytic pathway and a PI3K-independent dissociation from NHERF2. FRAP, acceptor photobleaching FRET, co-immunoprecipitation, PI3K inhibitor LY294002 in OK cells stably expressing NHERF2 Journal of cell science High 20571054
2010 NHERF2 ablation in murine intestine shifts NHE3 localization from the terminal web to microvilli and abolishes Ca²⁺-ionophore- and carbachol-mediated inhibition of NHE3, as well as STp (cGMP-mediated) inhibition, while forskolin-induced inhibition is preserved; NHERF2 tethers NHE3 near the terminal web. NHERF2 knockout mice, fluorometric NHE3 activity assay, immunolocalization, knockout validation The Journal of physiology High 20962002
2010 NHERF2 apical scaffolding enhances apical localization of PMCA2w/b in polarized MDCK cells by anchoring the pump to the apical actin cytoskeleton via ezrin, reducing pump internalization and lateral mobility; PMCA2x/b remains basolateral even with NHERF2 overexpression. Co-expression in polarized MDCK cells, surface biotinylation, FRAP, cytochalasin D/latrunculin B actin disruption, co-localization with ezrin The Journal of biological chemistry High 20663896
2010 NHERF-2 knockdown in astrocytes reduces GLAST glutamate transporter activity and protein half-life; endogenous GLAST and NHERF-2 robustly co-immunoprecipitate; the interaction is dependent on the last amino acid of GLAST's C-terminus. siRNA knockdown, co-immunoprecipitation with C-terminal deletion mutants, pulse-chase metabolic labeling, glutamate uptake assay Neuroscience letters High 20430067
2010 NHERF2 expression restricts P2Y1R and mGluR5 coupling to CaV2.2 calcium channels in sympathetic neurons without affecting M-current inhibition; this selective restriction requires the NHERF2-binding motif on the receptors, demonstrating NHERF2 determines receptor-to-ion-channel coupling specificity. Intranuclear cDNA injection in sympathetic neurons, electrophysiology of M-current and N-type Ca²⁺ current, P2Y1R DTSL-motif deletion mutant The Journal of neuroscience High 20720114
2010 NHERF2 and NHERF3 form the strongest heterodimerization among all NHERF family pairs; this heterodimerization requires NHERF2's PDZ domains and NHERF3's C-terminal PDZ recognition motif; the NHERF3-4A mutant defective in heterodimerization does not support carbachol-induced NHE3 inhibition. Pulldown, co-immunoprecipitation, FRET, FRAP, functional NHE3 inhibition assay with NHERF3-4A mutant The Journal of biological chemistry High 24867958
2011 NHERF2 is necessary for normal basal NHE3 activity and apical localization in mouse distal ileum; NHERF2-null ileum shows reduced brush border NHE3, and cAMP, cGMP, and Ca²⁺ (UTP) all fail to inhibit NHE3, while hyperosmolar inhibition is preserved; LPA stimulation of NHE3 is NHERF2-dependent. NHERF2-null mouse model, two-photon microscopy/SNARF-4F NHE3 activity assay, immunofluorescence American journal of physiology. Cell physiology High 21430287
2011 Elevated intracellular Ca²⁺ acutely abolishes the NHERF2-NHE3 FRET signal within 1 min in opossum kidney cell microvilli, transiently increasing NHE3 mobility; the association is re-established by ~60 min; NHERF1-NHE3 association is not disrupted by elevated Ca²⁺. FRET (acceptor photobleaching), FRAP, co-immunoprecipitation in polarized OK cells The Journal of biological chemistry High 21799002
2012 CaMKII inhibits basal NHE3 activity by a NHERF2-dependent process; CaMKIIγ constitutively binds NHE3 between aa 586-605 in a Ca²⁺-dependent manner (less association when Ca²⁺ is elevated); CaMKII phosphorylates NHE3 under basal conditions at sites downstream of aa 690. CaMKII inhibitors (KN-93, KN-62), co-immunoprecipitation domain mapping, back phosphorylation assay, NHERF2 requirement established by cell model The Journal of biological chemistry High 22371496
2012 NHERF2 scaffolds a megalin-ClC-5 complex in proximal tubule cells; NHERF2 interacts with megalin via an internal NHERF binding domain in megalin's C-terminus and PDZ2 of NHERF2; siRNA silencing of NHERF2 abolishes the megalin-ClC-5 interaction without affecting megalin protein levels. GST pulldown, immunoprecipitation from rat kidney lysate, siRNA knockdown, fusion protein reconstitution The international journal of biochemistry & cell biology High 22349218
2013 NHERF2 is more slowly mobile in brush border microvilli than NHERF1 or NHERF3; its slower mobility is determined by a unique C-terminal domain (including a non-conserved region plus ERM-binding domain); this C-terminal domain is also required for LPA stimulation of NHE3 activity/mobility and Ca²⁺ ionophore inhibition of NHE3. FRAP/confocal microscopy, chimeras and point mutants of NHERF1/2, functional NHE3 activity assays The Journal of biological chemistry High 23612977
2013 E3KARP (NHERF2) localizes to the base of microvilli (not along the full length like EBP50/NHERF1); this differential localization is determined by E3KARP's tail region; E3KARP exchanges more slowly from microvilli than EBP50, and this difference is also tail-determined. FRAP in live epithelial cells, chimeric tail constructs, proteomic pulldown Molecular biology of the cell Medium 23985317
2014 LPA stimulation of NHE3 exocytosis requires NHERF2, and operates through an ERK-PLC-PKCδ signaling module that dynamically and reversibly releases NHE3 from NHERF2; PKCδ is necessary for LPA-stimulated NHE3 mobility and NHE3/NHERF2 dissociation. FRAP, co-immunoprecipitation, PKCδ knockdown, ERK and PLC inhibitors, NHE3 activity in OK cells American journal of physiology. Cell physiology High 24760985
2014 NHERF2 interacts with estrogen receptor alpha (ERα) predominantly at the AF-1 domain and acts as a coactivator; overexpression of NHERF2 in MCF7 cells increases ERα transactivation, and NHERF2 together with SRC-1 synergistically enhances ERα activity at target gene promoters. Co-immunoprecipitation, ChIP at ERα target gene promoters, ERα transactivation reporter assays, stable overexpression in MCF7 Nucleic acids research Medium 24771346
2014 Crystal structure of NHERF2 PDZ1 domain in complex with LPA2 C-terminal peptide reveals that binding specificity is achieved through hydrogen bonds and hydrophobic contacts with the last four LPA2 residues; a small surface pocket adjacent to the ligand-binding site was identified. X-ray crystallography of PDZ1-LPA2 complex Biochemical and biophysical research communications High 24613836
2015 NHERF2 forms a complex with SCHIP1 and ezrin in podocyte foot processes; this complex is associated with cortical actin cytoskeleton dynamics in response to PDGF-BB signaling. Co-immunoprecipitation in cultured podocytes, immunofluorescence, zebrafish morpholino knockdown PloS one Medium 25807495
2015 NHERF2 contains an ERM-binding regulatory sequence (EBRS) located 19 residues upstream of the ERM-binding domain (EBD); EBRS facilitates NHERF2-ezrin interaction and is necessary for exclusive apical NHERF2 distribution in OK cells; phosphorylation of Ser303 in the EBRS decreases ezrin-binding affinity, dislocates NHERF2 to cytosol, increases NHERF2 mobility, and prevents dexamethasone stimulation of NHE3. EBRS deletion/point mutants, FRAP, co-immunoprecipitation with ezrin, phosphomimetic Ser303 mutants, NHE3 activity assays The Biochemical journal High 26251448
2015 E3KARP (NHERF2) exchange rate from microvilli is greatly enhanced during mitosis due to phosphorylation of Ser303 in its tail; A-Raf is required for Ser303 phosphorylation in mitotic cells; the S303D phosphomimetic mutation prevents E3KARP from substituting for EBP50 in microvillus formation. FRAP in mitotic cells, A-Raf RNAi, S303D phosphomimetic mutant, microvillus formation assay Molecular biology of the cell High 26310448
2017 Loss of NHERF1 and NHERF2 in human mast cells does not affect C3aR desensitization, internalization, ERK/Akt phosphorylation, or chemotaxis, but does inhibit C3a-induced degranulation, NF-κB activation, and chemokine production; C3aR does not associate with NHERF1 or NHERF2 despite having a PDZ motif. Lentiviral shRNA knockdown in human mast cells, functional degranulation, NF-κB and chemokine assays, co-immunoprecipitation (negative result for C3aR association) PloS one Medium 23284683
2019 HPV-16 and HPV-18 E6 oncoproteins interact with NHERF-2 via their PDZ-binding motifs and target NHERF-2 for proteasome-mediated degradation; E6-mediated NHERF-2 degradation leads to p27 downregulation and cyclin D1 upregulation, accelerating cell proliferation. Co-immunoprecipitation, proteasome inhibitor experiments, E6 PBM point mutants, NHERF-2 degradation assays in HPV-positive cervical tumor cells Journal of virology High 31597772
2023 NHERF2 stabilizes IκB protein by reducing its ubiquitination; SLC26A3 augments the NHERF2-IκB interaction, thereby inhibiting p65 nuclear translocation and NF-κB activity in colorectal cancer cells. Co-immunoprecipitation, ubiquitination assays, NF-κB reporter assays, p65 nuclear/cytoplasmic fractionation Oncogenesis Medium 37573425
2024 NHE3, NHERF2, and cGKII co-assemble in lipid raft microdomains of the small intestinal brush border membrane; NHERF2 is required for NHE3 raft association; Gucy2c activation decreases NHE3 raft association and shifts NHE3 from microvilli to terminal web in a cGKII- and NHERF2-dependent manner. Optiprep density gradient fractionation of Triton X-solubilized brush border membranes, NHERF2- and cGKII-knockout mice, confocal microscopy Acta physiologica High 38533975
2013 NHERF2 is necessary for agonist-induced ERM phosphorylation in pulmonary artery endothelial cells; NHERF2 associates with all three ERM proteins and co-immunoprecipitates with Rho kinase 2 (ROCK2); NHERF2 depletion prevents ROCK2-ERM association; a NHERF2 mutant unable to bind ERM attenuates cell attachment. Co-immunoprecipitation, siRNA knockdown, NHERF2 ERM-binding mutant, ECIS cell attachment measurement, Matrigel tube formation Cell communication and signaling Medium 24364877
2010 NHERF2 is required for cGMP- and Ca²⁺-dependent but not cAMP-dependent inhibition of NHE3 in Caco-2/bbe cells; simultaneous knockdown of both NHERF1 and NHERF2 is required to abolish cAMP inhibition; EGF stimulation of NHE3 is NHERF1-dependent (not NHERF2-dependent). Lentivirus shRNA stable knockdown and adenovirus siRNA transient knockdown in Caco-2/bbe cells, NHE3 activity assays American journal of physiology. Cell physiology High 21191106
2017 NHERF2 and NHERF3 have overlapping requirements in mouse jejunum for NHE3 regulation by LPA (stimulation) and by elevated Ca²⁺ and cGMP (inhibition); glucose-stimulated NHE3 activity is reduced in NHERF2- but not NHERF3-null mice. NHERF2 and NHERF3 knockout mice, two-photon microscopy/SNARF-4F NHE3 activity American journal of physiology. Gastrointestinal and liver physiology High 28882822

Source papers

Stage 0 corpus · 75 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Differential roles of NHERF1, NHERF2, and PDZK1 in regulating CFTR-mediated intestinal anion secretion in mice. The Journal of clinical investigation 303 19221439
1998 NHE3 kinase A regulatory protein E3KARP binds the epithelial brush border Na+/H+ exchanger NHE3 and the cytoskeletal protein ezrin. The Journal of biological chemistry 244 9748260
1998 The role of NHERF and E3KARP in the cAMP-mediated inhibition of NHE3. The Journal of biological chemistry 178 9792717
2000 E3KARP mediates the association of ezrin and protein kinase A with the cystic fibrosis transmembrane conductance regulator in airway cells. The Journal of biological chemistry 176 10893422
2005 Gp135/podocalyxin and NHERF-2 participate in the formation of a preapical domain during polarization of MDCK cells. The Journal of cell biology 165 15642748
2001 Glucocorticoid activation of Na(+)/H(+) exchanger isoform 3 revisited. The roles of SGK1 and NHERF2. The Journal of biological chemistry 153 11751930
2002 Ca(2+)-dependent inhibition of Na+/H+ exchanger 3 (NHE3) requires an NHE3-E3KARP-alpha-actinin-4 complex for oligomerization and endocytosis. The Journal of biological chemistry 106 11948184
2002 The serum and glucocorticoid-inducible kinase SGK1 and the Na+/H+ exchange regulating factor NHERF2 synergize to stimulate the renal outer medullary K+ channel ROMK1. Journal of the American Society of Nephrology : JASN 105 12444200
2001 Oligomerization of NHERF-1 and NHERF-2 PDZ domains: differential regulation by association with receptor carboxyl-termini and by phosphorylation. Biochemistry 100 11456497
2009 Lysophosphatidic acid stimulates the intestinal brush border Na(+)/H(+) exchanger 3 and fluid absorption via LPA(5) and NHERF2. Gastroenterology 95 19800338
2000 Hierarchy of merlin and ezrin N- and C-terminal domain interactions in homo- and heterotypic associations and their relationship to binding of scaffolding proteins EBP50 and E3KARP. The Journal of biological chemistry 85 11106646
2003 Ca2+-dependent inhibition of NHE3 requires PKC alpha which binds to E3KARP to decrease surface NHE3 containing plasma membrane complexes. American journal of physiology. Cell physiology 82 12954600
2002 The adenosine 2b receptor is recruited to the plasma membrane and associates with E3KARP and Ezrin upon agonist stimulation. The Journal of biological chemistry 82 12080047
2005 cGMP inhibition of Na+/H+ antiporter 3 (NHE3) requires PDZ domain adapter NHERF2, a broad specificity protein kinase G-anchoring protein. The Journal of biological chemistry 80 15722341
2005 P2Y1 receptor signaling is controlled by interaction with the PDZ scaffold NHERF-2. Proceedings of the National Academy of Sciences of the United States of America 79 15901899
2002 The down regulated in adenoma (dra) gene product binds to the second PDZ domain of the NHE3 kinase A regulatory protein (E3KARP), potentially linking intestinal Cl-/HCO3- exchange to Na+/H+ exchange. Biochemistry 77 12369822
2004 NHERF2 specifically interacts with LPA2 receptor and defines the specificity and efficiency of receptor-mediated phospholipase C-beta3 activation. Molecular and cellular biology 76 15143197
2002 Distinct cell type-specific expression of scaffolding proteins EBP50 and E3KARP: EBP50 is generally expressed with ezrin in specific epithelia, whereas E3KARP is not. European journal of cell biology 68 11893083
2004 Regulation of the epithelial Ca2+ channel TRPV5 by the NHE regulating factor NHERF2 and the serum and glucocorticoid inducible kinase isoforms SGK1 and SGK3 expressed in Xenopus oocytes. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 67 15319523
2001 Identification of EPI64, a TBC/rabGAP domain-containing microvillar protein that binds to the first PDZ domain of EBP50 and E3KARP. The Journal of cell biology 66 11285285
2005 Requirement of PDZ domains for the stimulation of the epithelial Ca2+ channel TRPV5 by the NHE regulating factor NHERF2 and the serum and glucocorticoid inducible kinase SGK1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 57 15665527
2003 Concerted roles of SGK1 and the Na+/H+ exchanger regulatory factor 2 (NHERF2) in regulation of NHE3. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 56 12649600
2008 The peptide transporter PEPT2 is targeted by the protein kinase SGK1 and the scaffold protein NHERF2. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 55 19088452
2010 MAGI-3 competes with NHERF-2 to negatively regulate LPA2 receptor signaling in colon cancer cells. Gastroenterology 53 21134377
2006 The PDZ scaffold NHERF-2 interacts with mGluR5 and regulates receptor activity. The Journal of biological chemistry 50 16891310
2010 NHERF1 and NHERF2 are necessary for multiple but usually separate aspects of basal and acute regulation of NHE3 activity. American journal of physiology. Cell physiology 49 21191106
1998 Genomic structure and sequence of a human homologue (NTHL1/NTH1) of Escherichia coli endonuclease III with those of the adjacent parts of TSC2 and SLC9A3R2 genes. Gene 40 9831664
2011 NHERF2 is necessary for basal activity, second messenger inhibition, and LPA stimulation of NHE3 in mouse distal ileum. American journal of physiology. Cell physiology 38 21430287
2010 Binding to Na(+) /H(+) exchanger regulatory factor 2 (NHERF2) affects trafficking and function of the enteropathogenic Escherichia coli type III secretion system effectors Map, EspI and NleH. Cellular microbiology 38 20618342
2010 Loss of PDZ-adaptor protein NHERF2 affects membrane localization and cGMP- and [Ca2+]- but not cAMP-dependent regulation of Na+/H+ exchanger 3 in murine intestine. The Journal of physiology 33 20962002
2005 NHERF2/SIP-1 interacts with mouse SRY via a different mechanism than human SRY. The Journal of biological chemistry 31 16166090
2004 Expression of TRPC4 channel protein that interacts with NHERF-2 in rat descending vasa recta. American journal of physiology. Cell physiology 29 15590898
2010 Apical scaffolding protein NHERF2 modulates the localization of alternatively spliced plasma membrane Ca2+ pump 2B variants in polarized epithelial cells. The Journal of biological chemistry 26 20663896
2012 The interaction between megalin and ClC-5 is scaffolded by the Na⁺-H⁺ exchanger regulatory factor 2 (NHERF2) in proximal tubule cells. The international journal of biochemistry & cell biology 25 22349218
2010 NHE3 mobility in brush borders increases upon NHERF2-dependent stimulation by lyophosphatidic acid. Journal of cell science 21 20571054
2002 Expression of NHERF-1, NHERF-2, PDGFR-alpha, and PDGFR-beta in normal human kidneys and in renal transplant rejection. Pathobiology : journal of immunopathology, molecular and cellular biology 20 12865627
1993 Sequence analysis of tka(-)-1 and tkb(+)-1 alleles in L5178Y tk+/- mouse-lymphoma cells and spontaneous tk-/- mutants. Mutation research 20 7681542
2022 Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal Na+/H+ Exchanger 3 Activity Through a PKC (Protein Kinase C)-Mediated NHERF1 and NHERF2 Pathway. Hypertension (Dallas, Tex. : 1979) 18 35674015
2012 NHERF-2 maintains endothelial homeostasis. Blood 18 22343917
2008 Urine electrolyte, mineral, and protein excretion in NHERF-2 and NHERF-1 null mice. American journal of physiology. Renal physiology 18 18256311
2006 NHE3 inhibits PKA-dependent functional expression of CFTR by NHERF2 PDZ interactions. Biochemical and biophysical research communications 18 16824484
2004 Lysophosphatidic acid induces exocytic trafficking of Na(+)/H(+) exchanger 3 by E3KARP-dependent activation of phospholipase C. Biochimica et biophysica acta 18 15238220
2013 The tails of apical scaffolding proteins EBP50 and E3KARP regulate their localization and dynamics. Molecular biology of the cell 17 23985317
2011 Elevated calcium acutely regulates dynamic interactions of NHERF2 and NHE3 proteins in opossum kidney (OK) cell microvilli. The Journal of biological chemistry 17 21799002
2015 Schip1 is a novel podocyte foot process protein that mediates actin cytoskeleton rearrangements and forms a complex with Nherf2 and ezrin. PloS one 16 25807495
2014 NHERF2/NHERF3 protein heterodimerization and macrocomplex formation are required for the inhibition of NHE3 activity by carbachol. The Journal of biological chemistry 16 24867958
2013 NHERF2 protein mobility rate is determined by a unique C-terminal domain that is also necessary for its regulation of NHE3 protein in OK cells. The Journal of biological chemistry 16 23612977
2019 PDZ Domain-Containing Protein NHERF-2 Is a Novel Target of Human Papillomavirus 16 (HPV-16) and HPV-18. Journal of virology 15 31597772
2014 Lysophosphatidic acid stimulation of NHE3 exocytosis in polarized epithelial cells occurs with release from NHERF2 via ERK-PLC-PKCδ signaling. American journal of physiology. Cell physiology 15 24760985
2014 SIP1/NHERF2 enhances estrogen receptor alpha transactivation in breast cancer cells. Nucleic acids research 15 24771346
2012 Calmodulin kinase II constitutively binds, phosphorylates, and inhibits brush border Na+/H+ exchanger 3 (NHE3) by a NHERF2 protein-dependent process. The Journal of biological chemistry 15 22371496
2017 Both NHERF3 and NHERF2 are necessary for multiple aspects of acute regulation of NHE3 by elevated Ca2+, cGMP, and lysophosphatidic acid. American journal of physiology. Gastrointestinal and liver physiology 13 28882822
2012 Roles for NHERF1 and NHERF2 on the regulation of C3a receptor signaling in human mast cells. PloS one 13 23284683
2004 NHERF2 increases platelet-derived growth factor-induced proliferation through PI-3-kinase/Akt-, ERK-, and Src family kinase-dependent pathway. Cellular signalling 13 15115658
2017 NHERF1 and NHERF2 regulation of SR-B1 stability via ubiquitination and proteasome degradation. Biochemical and biophysical research communications 12 28669731
2017 CFTR-NHERF2-LPA₂ Complex in the Airway and Gut Epithelia. International journal of molecular sciences 12 28869532
2013 NHERF2 is crucial in ERM phosphorylation in pulmonary endothelial cells. Cell communication and signaling : CCS 12 24364877
2010 GLAST stability and activity are enhanced by interaction with the PDZ scaffold NHERF-2. Neuroscience letters 12 20430067
2006 Astrocytic and neuronal localization of the scaffold protein Na+/H+ exchanger regulatory factor 2 (NHERF-2) in mouse brain. The Journal of comparative neurology 12 16374813
2014 Structural insights into PDZ-mediated interaction of NHERF2 and LPA(2), a cellular event implicated in CFTR channel regulation. Biochemical and biophysical research communications 11 24613836
2010 The scaffold protein NHERF2 determines the coupling of P2Y1 nucleotide and mGluR5 glutamate receptor to different ion channels in neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 11 20720114
2011 Alterations in the proteome of the NHERF2 knockout mouse jejunal brush border membrane vesicles. Physiological genomics 10 21427361
2011 Regulation of apical membrane enrichment and retention of plasma membrane Ca ATPase splice variants by the PDZ-domain protein NHERF2. Communicative & integrative biology 10 21980575
2012 Modulatory roles of NHERF1 and NHERF2 in cell surface expression of the glutamate transporter GLAST. Biochemical and biophysical research communications 9 23200831
2010 Concerted actions of NHERF2 and WNK4 in regulating TRPV5. Biochemical and biophysical research communications 9 21187068
2015 The NHERF2 sequence adjacent and upstream of the ERM-binding domain affects NHERF2-ezrin binding and dexamethasone stimulated NHE3 activity. The Biochemical journal 8 26251448
2009 Refined genomic localization of the genetic lesion in the osteopetrosis (op) rat and exclusion of three positional and functional candidate genes, Clcn7, Atp6v0c, and Slc9a3r2. Calcified tissue international 7 19259722
2023 SLC26A3/NHERF2-IκB/NFκB/p65 feedback loop suppresses tumorigenesis and metastasis in colorectal cancer. Oncogenesis 6 37573425
2025 NHERF2 as a Novel Biomarker for Distinguishing MAC Pulmonary Disease from Tuberculosis Based on Proteome Analysis of Serum Extracellular Vesicles. International journal of molecular sciences 4 39940923
2015 The function and dynamics of the apical scaffolding protein E3KARP are regulated by cell-cycle phosphorylation. Molecular biology of the cell 4 26310448
2023 HPV16 Impacts NHERF2 Expression in Oropharyngeal Cancers. Pathogens (Basel, Switzerland) 2 37623973
2011 A novel porcine gene--SLC9A3R2, differentially expressed in the longissimus muscle tissues from Meishan and Large White pigs. Folia biologica 2 21457650
2024 cGMP-dependent kinase 2, Na+/H+ exchanger NHE3, and PDZ-adaptor NHERF2 co-assemble in apical membrane microdomains. Acta physiologica (Oxford, England) 1 38533975
2005 Overexpression, purification, and characterization of PDZ domain proteins NHERF and E3KARP in Escherichia coli. Protein expression and purification 1 15721789
2026 Multi-omics Data Reveal SLC9A3R2 Promotes Breast Cancer Progression and an Immunosuppressive Microenvironment. Journal of Cancer 0 42179786

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