Affinage

LNX1

E3 ubiquitin-protein ligase LNX · UniProt Q8TBB1

Length
728 aa
Mass
80.6 kDa
Annotated
2026-06-10
37 papers in source corpus 24 papers cited in narrative 24 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

LNX1 is a RING-type E3 ubiquitin ligase that couples PDZ-domain-mediated substrate recognition to ubiquitin transfer, functioning both as a degradative ligase and as a multidomain signalling scaffold (PMID:11782429, PMID:11922143). Its isolated RING finger has E2-dependent ligase activity that is abolished by mutation of a conserved RING cysteine, and structural work shows the catalytic RING is embedded between two zinc-finger motifs (Zn-RING-Zn) and operates as a heterodimer that recruits the E2 Ubc13/Ube2V2, with ubiquitin from one monomer bridging the partner monomer to enable catalysis (PMID:11782429, PMID:29496391). Substrate selection is governed largely by its tandem PDZ domains, which engage C-terminal motifs of target proteins—for example a carboxyl-terminal cysteine motif binding PDZ2 in liprin-α1, and PDZ-dependent recognition of connexin36, CAR, and others (PMID:12468544, PMID:29121065, PMID:30295974). Through this architecture LNX1 directs K48-linked polyubiquitination and proteasomal degradation of a broad substrate set including Numb, where degradation relieves Numb-mediated inhibition of Notch and promotes Notch signalling and glioma stem cell expansion (PMID:11782429, PMID:33255632), the dorsal determinant Bozozok to restrict axis formation in zebrafish (PMID:19668196), the kinases PBK and BCR to control proliferation and apoptosis (PMID:22889411), and p53 in an MDM2-dependent manner to limit p53 stability and tumor suppression (PMID:31533005). LNX1 also performs non-degradative ubiquitination of RhoC (but not RhoA), activating RhoC by acting on the RhoGDI-RhoC interaction under negative control by LIS1 (PMID:36192543). In neurons LNX1 is concentrated postsynaptically where it stabilizes EphB1/EphB2 receptors at the membrane by preventing their internalization, a function required for mossy fiber targeting, dendritic spine and NMDAR-dependent synaptic maturation, and social memory (PMID:30185604, PMID:31772302, PMID:35531068); it additionally ubiquitinates the glycine transporter GlyT2 at a C-terminal lysine cluster to regulate transport activity (PMID:31628376). A RING-deficient neuronal isoform, LNX1p70, retains scaffolding activity and can promote ubiquitination of shared substrates by recruiting other E3 ligases (PMID:29121065).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 Medium

    Established LNX1 as a Numb-interacting protein, defining the molecular handle (the Numb PTB domain binding the LDNPAY motif) that would later connect LNX1 to Notch regulation.

    Evidence Yeast two-hybrid with mutational and peptide-competition validation

    PMID:9535908

    Open questions at the time
    • No enzymatic activity yet attributed to LNX1
    • Functional consequence of the interaction unknown at this stage
  2. 2002 High

    Defined LNX1 as a functional RING E3 ligase that ubiquitinates and degrades Numb, mechanistically linking LNX1 to enhanced Notch signalling.

    Evidence In vitro ligase assay, RING cysteine active-site mutagenesis, in vivo ubiquitination and proteasome-inhibitor experiments

    PMID:11782429

    Open questions at the time
    • E2 partner not identified
    • Structural basis of catalysis unknown
    • Which PDZ domains recognize which substrates not yet mapped
  3. 2001 Medium

    Showed LNX1 can oligomerize and bind Numb simultaneously, framing LNX1 as a molecular scaffold in addition to a ligase.

    Evidence Protein interaction and yeast two-hybrid assays of PDZ- and RING-mediated oligomerization

    PMID:11922143

    Open questions at the time
    • Functional importance of oligomerization for catalysis untested
    • No in vitro reconstitution
  4. 2002 Medium

    Identified PDZ-domain-based substrate/partner recognition (CAR via PDZ2), beginning the mapping of how individual PDZ domains select targets.

    Evidence Yeast two-hybrid, reciprocal in vivo/in vitro binding with domain mapping, colocalization

    PMID:12468544

    Open questions at the time
    • Whether CAR is a ubiquitination substrate not shown
    • Physiological role of LNX1-CAR interaction unknown
  5. 2009 High

    Demonstrated an in vivo developmental role: LNX1 K48-polyubiquitinates Bozozok to restrict dorso-ventral axis formation, validating substrate-binding-motif-dependent degradation in a whole animal.

    Evidence Zebrafish morpholino knockdown, K48 ubiquitination assays, genetic epistasis, substrate motif mutagenesis

    PMID:19668196

    Open questions at the time
    • Mammalian developmental relevance not addressed
    • Which PDZ domain binds Boz not specified
  6. 2009 Low

    Extended the LNX1 interactome to the small GTPase RhoC via PDZ1, hinting at a non-canonical signalling output.

    Evidence Yeast two-hybrid, co-IP, subcellular localization, AP-1 reporter assay

    PMID:19701800

    Open questions at the time
    • Ubiquitination of RhoC not yet demonstrated
    • Mechanism linking RhoC relocalization to AP-1 activity unclear
  7. 2011 Medium

    Broadened the LNX1 PDZ-domain interactome through array and phylogenetic approaches, supporting a general scaffolding function shared with MUPP1.

    Evidence Human protein array with co-IP validation; yeast two-hybrid with phylogenetic analysis

    PMID:21827680 PMID:22087225

    Open questions at the time
    • Most identified partners not tested as ubiquitination substrates
    • Physiological significance of individual interactions untested
  8. 2012 Medium

    Identified PBK and BCR as endogenous substrates and connected LNX1-mediated degradation to control of proliferation and apoptotic sensitivity.

    Evidence Yeast two-hybrid peptide library, in vitro and in vivo ubiquitination, proliferation and apoptosis assays

    PMID:22889411

    Open questions at the time
    • In vivo tumor relevance not tested
    • Specificity determinants among many PDZ ligands unresolved
  9. 2014 Medium

    Revealed isoform-specific regulation, showing LNX1p70 expression is restrained translationally by 5'UTR uORFs while LNX1p80 is controlled by proteasomal turnover.

    Evidence Luciferase reporter assays and uORF mutational analysis

    PMID:25200495

    Open questions at the time
    • Physiological triggers that relieve translational repression unknown
    • Tissue distribution of isoform regulation not defined
  10. 2017 Medium

    Mapped PDZ2-dependent recognition of liprin-α1 and identified the RING-deficient LNX1p70 isoform as a scaffold able to promote substrate ubiquitination by recruiting other E3 ligases (TRIM family).

    Evidence AP-MS interactome, in vitro ubiquitination, co-IP, PDZ-binding-motif mutagenesis

    PMID:29121065

    Open questions at the time
    • Which recruited E3 catalyzes p70-dependent ubiquitination not directly shown
    • Cellular consequences for most substrates untested
  11. 2018 High

    Provided the structural mechanism: a Zn-RING-Zn module forms a catalytic heterodimer recruiting Ubc13/Ube2V2, explaining how LNX1 transfers ubiquitin.

    Evidence Crystal structure of LNX1 ubiquitination domain with Ubc13~Ub, mutagenesis, in vitro ubiquitination

    PMID:29496391

    Open questions at the time
    • Chain-type specificity in vivo not fully defined
    • Structure of PDZ-substrate engagement not solved
  12. 2018 High

    Defined LNX1 neuronal substrate connexin36 and a developmental role for postsynaptic LNX1 in stabilizing EphB receptors and shaping CA3 mossy fiber circuitry.

    Evidence Co-IP/pull-down with PDZ2, ligase-competent vs ligase-dead comparison; Lnx1 knockout mice with morphology, complex Co-IP, proteasome inhibition, EphB2 rescue

    PMID:30185604 PMID:30295974

    Open questions at the time
    • Direct ubiquitination of EphB receptors not biochemically demonstrated
    • How ligase activity and stabilization (non-degradative) coexist unresolved
  13. 2019 High

    Expanded LNX1 into transporter regulation, immune/oncogenic signalling, and tumor suppressor control: RING-dependent GlyT2 ubiquitination, LDOC1-dependent pJAK2 degradation, and MDM2-dependent p53 destabilization, plus an essential synaptic role in social memory via the Lnx1-NMDAR-EphB2 complex.

    Evidence In vitro ubiquitination with lysine mutagenesis and LNX2 KO; co-IP and ubiquitination assays; CRISPR KO with p53 half-life and xenograft readouts; KO mice with electrophysiology, PSD fractionation, and viral rescue

    PMID:30634502 PMID:31533005 PMID:31628376 PMID:31772302

    Open questions at the time
    • Degree of functional overlap with LNX2 across substrates not delineated
    • How LNX1 partitions between degradative and stabilizing roles in neurons unclear
  14. 2020 Medium

    Connected LNX1 to disease contexts—NEK6 degradation controlled by miR-325-3p during M. tuberculosis infection, and post-temozolomide Numb degradation driving Notch1 activation and glioma stem cell expansion.

    Evidence miRNA targeting, Mir325 KO mice, NEK6 ubiquitination/STAT3 readouts; patient-derived xenograft gain/loss-of-function with Numb/NICD readouts and survival model

    PMID:32487755 PMID:33255632

    Open questions at the time
    • Therapeutic targetability not established
    • Generality across tumor types untested
  15. 2022 Medium

    Resolved a non-degradative output: LNX1 activates RhoC (not RhoA) via non-degrading ubiquitination acting on the RhoGDI-RhoC interaction, under LIS1 negative regulation, and reaffirmed EphB stabilization driving synaptogenesis.

    Evidence Isoform-specific in vitro ubiquitination, RhoGDI-RhoC interaction and LIS1 inhibition assays; KO mice with EphB internalization, spine morphology, and EphB2 rescue

    PMID:35531068 PMID:36192543

    Open questions at the time
    • Ubiquitin chain type/site on RhoC not fully defined
    • How LIS1 mechanistically blocks LNX1 unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how LNX1 selects between degradative and non-degradative/stabilizing fates for its many PDZ-bound substrates, and how isoform identity, E2 choice, and partner ligases dictate outcome in a given cellular context.
  • No unifying model for substrate fate determination
  • Structure of PDZ-substrate complexes lacking
  • In vivo chain-type specificity per substrate undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016874 ligase activity 5 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-1266738 Developmental Biology 3
Partners
CXADREPHB2GLYT2LDOC1MDM2NUMBPPFIA1RHOC
Complex memberships
LDOC1-pJAK2-LNX1 complexLNX1-MDM2-p53 complexLNX1-NMDAR-EphB2 postsynaptic complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 LNX1 was identified as a novel protein that interacts specifically with the Numb PTB domain via the sequence motif LDNPAY. Mutational analysis and peptide competition experiments showed that tyrosine phosphorylation within this motif was not required for Numb PTB domain binding. Phosphorylation of tyrosine in LDNPAY could generate a binding site for other PTB domain-containing proteins such as SHC. Yeast two-hybrid screen, mutational analysis, peptide competition experiments The Journal of biological chemistry Medium 9535908
2002 LNX1 functions as a RING-type E3 ubiquitin ligase; its isolated RING finger domain has E2-dependent ubiquitin ligase activity in vitro, and mutation of a conserved cysteine residue within the RING domain abolishes this activity. Numb is a substrate of LNX1 E3 activity both in vitro and in vivo. A region including the Numb PTB domain-binding site and the first PDZ domain is required for Numb ubiquitylation. Expression of wild-type but not mutant LNX causes proteasome-dependent degradation of Numb and can enhance Notch signalling. In vitro ubiquitin ligase assay, active-site mutagenesis (RING domain cysteine mutation), in vivo ubiquitination assay, proteasome inhibitor experiments The EMBO journal High 11782429
2001 LNX1 and LNX2 form oligomers via their PDZ domains binding to PDZ-binding consensus motifs located in their C-termini, or by homophilic oligomerization of their RING fingers. LNX proteins bind Numb and Numblike via their NPXY motifs, and oligomerization and Numb binding occur simultaneously, suggesting LNX proteins serve as molecular scaffolds. Protein interaction assays, yeast two-hybrid, molecular biology Molecular and cellular neurosciences Medium 11922143
2002 LNX1 interacts with the intracellular tail of the Coxsackievirus and adenovirus receptor (CAR) both in vivo and in vitro. Efficient binding required not only the consensus PDZ domain-binding motif in the C-terminus of CAR but also upstream sequences. The CAR binding region in LNX1 was mapped to the second PDZ domain. CAR and LNX1 colocalize in mammalian cells. Yeast two-hybrid screen, in vivo and in vitro binding assays, colocalization by immunostaining The Journal of biological chemistry Medium 12468544
2005 LNX1 directly interacts with the ErbB2 receptor and is specifically localized in perisynaptic Schwann cells at the neuromuscular junction but not in Schwann cells along the motor axon. LNX1 protein levels are inversely correlated with the responsiveness of perisynaptic Schwann cells to neuregulin-1, and LNX1 staining disappears upon denervation while ErbB2 reappears. Co-immunoprecipitation, immunostaining/localization, denervation experiments Molecular and cellular neurosciences Medium 16122940
2005 Human LNX1 interacts with SKIP (Ski interacting protein) via its PDZ domains. This interaction was confirmed by co-immunoprecipitation in HEK293 cells. LNX1 can affect the subcellular localization of Numb, suggesting LNX1 functions as a molecular anchor that localizes Numb to the subcellular site of its interaction with Notch. Yeast two-hybrid, co-immunoprecipitation, subcellular localization assay The international journal of biochemistry & cell biology Low 16002321
2009 LNX1 (Lnx-like/Lnx-2b in zebrafish) was identified as a critical E3 ubiquitin ligase that binds Bozozok (Boz) and induces K48-linked polyubiquitylation of Boz leading to its proteasomal degradation, thereby restricting dorso-ventral axis formation. Dorsalization by Boz overexpression was suppressed by raising Lnx-l levels but not when Boz lacked the critical Lnx-l binding motif. Morpholino knockdown in zebrafish, K48-linked ubiquitination assay in 293T cells and zebrafish, genetic epistasis (double morpholino/overexpression), binding assays Nature cell biology High 19668196
2009 LNX1 interacts with RhoC (a Ras family small GTPase) via its first PDZ domain, as shown by yeast two-hybrid and co-immunoprecipitation in mammalian cells. Co-expression of LNX1 causes RhoC to change its sublocalization from cytoplasm to nucleus. Co-expression of RhoC reduced the transcriptional activity of AP-1, which was upregulated by LNX1 overexpression alone. Yeast two-hybrid, co-immunoprecipitation, subcellular localization assay, AP-1 reporter assay Molecular biology reports Low 19701800
2011 LNX1 PDZ domains are phylogenetically related to PDZ domains in MUPP1 and share common binding specificities with MUPP1 ligands. Novel LNX1 interactions with three known MUPP1 ligands were identified by yeast two-hybrid assays, supporting functional conservation between LNX and MUPP1 PDZ domains. Yeast two-hybrid assays, phylogenetic analysis BMC evolutionary biology Low 21827680
2011 A human protein array screen identified 53 potential direct LNX1 PDZ domain binding partners from 8,000 human proteins. Six novel LNX1 binding partners were confirmed: KCNA4, PAK6, PLEKHG5, PKC-alpha1, TYK2, and PBK. These interactions suggest LNX1 functions as a signalling scaffold. Human protein array, co-immunoprecipitation validation PloS one Medium 22087225
2012 LNX1 ubiquitinates substrates via its PDZ domains binding to C-termini of target proteins. PDZ-binding kinase (PBK) and BCR were identified and confirmed as novel endogenous LNX1 substrates in vivo. LNX1-mediated ubiquitination and degradation of PBK inhibited cell proliferation and enhanced sensitivity to doxorubicin-induced apoptosis. Yeast two-hybrid peptide library screen, in vitro ubiquitination assay, in vivo substrate validation, cell proliferation and apoptosis assays Journal of proteome research Medium 22889411
2014 The 5' untranslated region of the Lnx1_variant 2 mRNA (generating LNX1p70 isoform) strongly suppresses protein production, mediated in part by upstream open reading frames (uORFs) and a sequence element that decreases mRNA levels and translational efficiency. By contrast, protein turnover via proteasomal degradation influences LNX1p80 levels. Luciferase reporter assays, uORF mutational analysis Gene Medium 25200495
2017 LNX1 ubiquitinates PPFIA1 (liprin-α1), KLHL11, KIF7, and ERC2 as substrates. LNX1 ubiquitination of liprin-α1 is dependent on a PDZ-binding motif containing a carboxyl-terminal cysteine that binds LNX1 PDZ2. The neuronal LNX1p70 isoform (lacking the RING domain) can also promote ubiquitination of PPFIA1 and KLHL11, possibly by acting as a scaffold recruiting other E3 ligases. LNX1 interacts with MID2/TRIM1 and TRIM27. Affinity purification/mass spectrometry, in vitro ubiquitination assays, co-immunoprecipitation, mutational analysis of PDZ-binding motif PloS one Medium 29121065
2018 The crystal structure of the LNX1 ubiquitination domain in complex with Ubc13~Ubiquitin was determined. The RING domain of LNX1 is embedded between two zinc-finger motifs (Zn-RING-Zn), both required for ubiquitination activity. In the heterodimeric complex, ubiquitin from one monomer shares more buried surface area with LNX1 of the other monomer, and these interactions are essential for catalysis. Ubc13/Ube2V2 was identified as a functional E2 for LNX1 in vitro. Crystal structure determination, in vitro ubiquitination assay, mutagenesis Journal of molecular biology High 29496391
2018 LNX1 and LNX2 directly interact with connexin36 (Cx36), the key component of gap junctions forming electrical synapses in the mammalian CNS. Interaction was demonstrated by coimmunoprecipitation and pull-down with the second PDZ domain of LNX1/LNX2. Cotransfection of cells with Cx36 and E3 ligase-competent LNX1/LNX2 isoforms led to loss of Cx36-containing gap junctions, whereas isoforms lacking ligase activity did not cause this loss, suggesting LNX mediates ubiquitination of Cx36 with consequent Cx36 internalization. Immunofluorescence colocalization, co-immunoprecipitation, pull-down with isolated PDZ domains, cotransfection with ligase-competent vs. ligase-dead isoforms The European journal of neuroscience Medium 30295974
2018 Postsynaptic Lnx1 in hippocampal CA3 pyramidal neurons is essential for mossy fiber axon targeting and terminal maturation. Lnx1 deletion causes defective synaptic arrangement and aberrant presynaptic terminals. EphB1 and EphB2 receptors were identified as novel Lnx1-binding proteins forming a multiprotein complex stabilized on the CA3 neuron membrane by prevention of proteasome activity. Constitutively active EphB2 kinase rescues MF terminal structure in Lnx1 mutant mice. Lnx1 knockout mice, synaptic morphology analysis, co-immunoprecipitation of EphB-Lnx1 complex, proteasome inhibitor experiments, constitutively active EphB2 rescue The Journal of cell biology High 30185604
2019 LNX1 and LNX2 ubiquitinate the presynaptic glycine transporter GlyT2. The N-terminal RING-finger domain of LNX1/2 ubiquitinates a cytoplasmic C-terminal lysine cluster in GlyT2 (K751, K773, K787, K791), regulating GlyT2 expression levels and transport activity. Genetic deletion of endogenous LNX2 in spinal cord primary neurons increases GlyT2 expression, and LNX2 is required for PKC-mediated control of GlyT2 transport. Unbiased screening, in vitro ubiquitination assays (RING domain), site-directed mutagenesis of lysine residues, LNX2 genetic knockout in neurons, transport activity assays Scientific reports High 31628376
2019 LDOC1 forms a multiprotein complex with phospho-JAK2 (pJAK2) and LNX1, targeting pJAK2 for ubiquitin-dependent proteasomal degradation. LDOC1 deficiency attenuates the interactions between LNX1 and pJAK2, leading to ineffective ubiquitination of pJAK2 and consequent activation of STAT3. Co-immunoprecipitation, immunofluorescent confocal microscopy, ubiquitination assay, knockdown/overexpression functional studies Cancers Medium 30634502
2019 Hippocampal CA3 Lnx1 is required for initial social memory and partner discrimination in juvenile mice. Lnx1 deletion causes NMDAR hypofunction attributable to decreased GluN2B expression in the PSD compartment and disruption of the Lnx1-NMDAR-EphB2 complex. Specific restoration of Lnx1 or EphB2 in CA3 of Lnx1-/- mice rescues defective synaptic function and social memory. Gene targeting (knockout mice), electrophysiology (NMDAR function), PSD fractionation and Western blotting, co-immunoprecipitation of Lnx1-NMDAR-EphB2 complex, stereotaxic viral rescue Molecular psychiatry High 31772302
2019 LNX1 interacts with p53 and MDM2, and increases ubiquitination of p53 in an MDM2-dependent manner, thereby decreasing p53 half-life and inhibiting p53-dependent transcription. LNX1 KO (by CRISPR) in p53 wild-type cancer cells increased p53 stability and p53-dependent transcription, and impaired tumor growth in vivo. Co-immunoprecipitation, CRISPR-Cas9 KO, ubiquitination assay, p53 half-life assay, tumor xenograft model FASEB journal Medium 31533005
2020 miR-325-3p directly targets LNX1 (as an E3 ubiquitin ligase of NEK6), and its upregulation after M. tuberculosis infection reduces LNX1 levels, hampers proteasomal degradation of NEK6, and leads to NEK6 accumulation. Abnormal NEK6 accumulation activates STAT3 signaling, inhibiting apoptosis and promoting intracellular M. tuberculosis survival. miR-325-3p target validation, LNX1 knockdown/overexpression, Mir325 knockout mice, NEK6 ubiquitination assay, STAT3 signaling readouts mBio Medium 32487755
2020 LNX1 is strongly upregulated after temozolomide therapy in glioblastoma and promotes Notch1 signaling by targeting negative regulator Numb for degradation. Overexpression of LNX1 results in Notch1 signaling activation and increased glioma stem cell populations; LNX1 knockdown reverses these changes and results in more prolonged survival in a mouse model. Gene set expression analysis, LNX1 overexpression/knockdown in patient-derived xenograft cells, Western blotting for Numb/NICD, mouse survival model Cancers Medium 33255632
2022 LNX1 mediates non-degrading ubiquitination (NDU) of RhoC (but not RhoA), activating RhoC. This ubiquitination is negatively regulated by LIS1 (PAFAH1B1): LIS1 inhibits LNX1's effects on the RhoGDI-RhoC interaction, providing a molecular mechanism for LIS1-dependent regulation of Rho GTPase activity. In vitro ubiquitination assay distinguishing RhoC vs RhoA, RhoGDI-RhoC interaction assay, LIS1 inhibition experiments Scientific reports Medium 36192543
2022 Lnx1 stabilizes EphB receptors (EphB1, EphB2) at the postsynaptic membrane; loss of Lnx1 promotes internalization of EphB receptors from the cell surface, leading to abnormal dendritic spine development and impaired synaptogenesis. Constitutively active EphB2 intracellular signaling rescues synaptogenesis in Lnx1 mutant mice. Lnx1 knockout mice, EphB receptor internalization assay, dendritic spine morphology analysis, constitutively active EphB2 rescue Frontiers in molecular neuroscience Medium 35531068

Source papers

Stage 0 corpus · 37 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 LNX functions as a RING type E3 ubiquitin ligase that targets the cell fate determinant Numb for ubiquitin-dependent degradation. The EMBO journal 156 11782429
1998 The mammalian numb phosphotyrosine-binding domain. Characterization of binding specificity and identification of a novel PDZ domain-containing numb binding protein, LNX. The Journal of biological chemistry 109 9535908
2002 The Coxsackievirus and adenovirus receptor (CAR) forms a complex with the PDZ domain-containing protein ligand-of-numb protein-X (LNX). The Journal of biological chemistry 83 12468544
2001 The Lnx family proteins function as molecular scaffolds for Numb family proteins. Molecular and cellular neurosciences 57 11922143
2020 MicroRNA-325-3p Facilitates Immune Escape of Mycobacterium tuberculosis through Targeting LNX1 via NEK6 Accumulation to Promote Anti-Apoptotic STAT3 Signaling. mBio 46 32487755
2005 LNX1 is a perisynaptic Schwann cell specific E3 ubiquitin ligase that interacts with ErbB2. Molecular and cellular neurosciences 35 16122940
2005 Characterization of human LNX, a novel ligand of Numb protein X that is downregulated in human gliomas. The international journal of biochemistry & cell biology 32 16002321
2011 Molecular evolution of the LNX gene family. BMC evolutionary biology 31 21827680
2012 Proteomics strategy to identify substrates of LNX, a PDZ domain-containing E3 ubiquitin ligase. Journal of proteome research 26 22889411
2009 Organizer restriction through modulation of Bozozok stability by the E3 ubiquitin ligase Lnx-like. Nature cell biology 24 19668196
2019 Novel STAT3 Inhibitor LDOC1 Targets Phospho-JAK2 for Degradation by Interacting with LNX1 and Regulates the Aggressiveness of Lung Cancer. Cancers 22 30634502
2011 Biochemical and computational analysis of LNX1 interacting proteins. PloS one 21 22087225
2018 Retrograde regulation of mossy fiber axon targeting and terminal maturation via postsynaptic Lnx1. The Journal of cell biology 19 30185604
2018 E3 ubiquitin ligases LNX1 and LNX2 localize at neuronal gap junctions formed by connexin36 in rodent brain and molecularly interact with connexin36. The European journal of neuroscience 17 30295974
2018 LNX1/LNX2 proteins: functions in neuronal signalling and beyond. Neuronal signaling 16 32714586
2016 Decreased Anxiety-Related Behaviour but Apparently Unperturbed NUMB Function in Ligand of NUMB Protein-X (LNX) 1/2 Double Knockout Mice. Molecular neurobiology 16 27889896
2009 LNX (Ligand of Numb-protein X) interacts with RhoC, both of which regulate AP-1-mediated transcriptional activation. Molecular biology reports 16 19701800
2020 LNX1 Modulates Notch1 Signaling to Promote Expansion of the Glioma Stem Cell Population during Temozolomide Therapy in Glioblastoma. Cancers 15 33255632
2019 E3 ubiquitin ligases LNX1 and LNX2 are major regulators of the presynaptic glycine transporter GlyT2. Scientific reports 15 31628376
2019 Hippocampal Lnx1-NMDAR multiprotein complex mediates initial social memory. Molecular psychiatry 15 31772302
2018 Structure of LNX1:Ubc13~Ubiquitin Complex Reveals the Role of Additional Motifs for the E3 Ligase Activity of LNX1. Journal of molecular biology 13 29496391
2017 Proteomic analysis reveals novel ligands and substrates for LNX1 E3 ubiquitin ligase. PloS one 13 29121065
2014 Tight, cell type-specific control of LNX expression in the nervous system, at the level of transcription, translation and protein stability. Gene 13 25200495
2010 Lnx-2b restricts gsc expression to the dorsal mesoderm by limiting Nodal and Bozozok activity. Biochemical and biophysical research communications 13 20971071
2019 Glycine Regulates Neural Stem Cell Proliferation During Development via Lnx1-Dependent Notch Signaling. Frontiers in molecular neuroscience 12 30833887
2022 Heme oxygenase-1 mitigates liver injury and fibrosis via modulation of LNX1/Notch1 pathway in myeloid cells. iScience 11 36093061
2001 Identification of a human LNX protein containing multiple PDZ domains. Biochemical genetics 11 11521506
2008 Mutation and copy number analysis of LNX1 and Numbl in nervous system tumors. Cancer genetics and cytogenetics 10 18940473
2020 The Molecular and Pathophysiological Functions of Members of the LNX/PDZRN E3 Ubiquitin Ligase Family. Molecules (Basel, Switzerland) 9 33333989
2019 LNX1 contributes to tumor growth by down-regulating p53 stability. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 8 31533005
2010 A global genomic view on LNX siRNA-mediated cell cycle arrest. Molecular biology reports 7 21104141
2022 Activation of RhoC by regulatory ubiquitination is mediated by LNX1 and suppressed by LIS1. Scientific reports 3 36192543
2021 LNX1 Contributes to Cell Cycle Progression and Cisplatin Resistance. Cancers 2 34439220
2022 Scaffold Protein Lnx1 Stabilizes EphB Receptor Kinases for Synaptogenesis. Frontiers in molecular neuroscience 1 35531068
2005 [Molecular cloning and identify expression of the novel human LNX gene in gliomas]. Zhonghua yi xue za zhi 1 16324299
2025 Differential neuronal functions of LNX1 and LNX2 revealed by behavioural analysis in single and double knockout mice. Behavioral and brain functions : BBF 0 40269869
2024 Identification of potential substrates of LNX1 in chicken cells. Poultry science 0 39693965

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