Affinage

NEGR1

Neuronal growth regulator 1 · UniProt Q7Z3B1

Length
354 aa
Mass
38.7 kDa
Annotated
2026-06-10
76 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NEGR1 (Kilon) is a brain-enriched, GPI-anchored cell adhesion molecule of the IgLON immunoglobulin superfamily that resides in Triton-insoluble lipid raft membranes and at cell-to-cell contact sites, where it governs neurite arborization, synapse number, and dendritic spine density during neural development (PMID:10075727, PMID:24382801, PMID:30059965). It engages in both homophilic and heterophilic adhesion (e.g. with OBCAM) and is concentrated at postsynaptic membranes (PMID:12617969). NEGR1 acts largely as a growth-factor signaling modulator: it physically interacts with FGFR2, reduces FGFR2 degradation from the plasma membrane, and sustains downstream ERK and AKT signaling, with FGFR2 overexpression rescuing the neuronal migration and spine defects of Negr1 loss (PMID:30059965). The metalloprotease ADAM10 sheds the NEGR1 ectodomain, and this soluble form promotes neurite outgrowth in an FGFR2- and ERK1/2-dependent manner (PMID:26793057). NEGR1 additionally binds LIFR to control LIF-induced Lcn2 expression supporting adult hippocampal neurogenesis, synaptic plasticity, and affective behavior (PMID:30651602), and binds NPC2 and the Na/K-ATPase beta1-subunit ATP1B1, linking it to cholesterol handling and membrane raft organization (PMID:27940359, PMID:32958118). Within neurons NEGR1 promotes palmitoylation-dependent clearance and vesicular targeting of GAD65 to maintain inhibitory GABA synthesis, and its loss reduces parvalbumin interneuron numbers and GABAergic synapse density (PMID:30932003, PMID:39676071). Loss of NEGR1 disrupts hypothalamic energy balance, olfactory neurogenesis, and Leydig-cell testosterone production, while its dysregulation in limbic circuits produces anxiety- and depression-like behaviors (PMID:39676071, PMID:40382479, PMID:40886916, PMID:25077509, PMID:39170714). Beyond the nervous system NEGR1 (IgLON4) modulates myogenic differentiation and constrains tumor cell migration and growth in ovarian cancer and neuroblastoma (PMID:25057311, PMID:36291131, PMID:37765276).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 High

    Established the molecular identity of NEGR1 as a GPI-anchored IgLON family adhesion protein, defining its membrane attachment and raft residence as the structural basis for all later signaling roles.

    Evidence cDNA cloning, PI-PLC solubilization, deglycosylation, and lipid raft fractionation in rat brain

    PMID:10075727

    Open questions at the time
    • No binding partner or signaling output identified
    • Function inferred only from family membership and localization
  2. 2003 High

    Showed NEGR1 mediates both homophilic and heterophilic adhesion and is postsynaptically enriched, framing it as an adhesion molecule acting at synaptic contacts.

    Evidence Cross-linker, immunoprecipitation, and EM immunohistochemistry in rat cortex/hippocampus

    PMID:12617969

    Open questions at the time
    • Functional consequence of OBCAM binding not tested
    • No downstream signaling defined
  3. 2005 Medium

    Demonstrated NEGR1 actively promotes neurite outgrowth and axon attraction, moving it from a static adhesion marker to a regulator of process growth.

    Evidence In vitro stripe assay and entorhinal cortex lesion model with immunohistochemistry

    PMID:15946856

    Open questions at the time
    • Receptor/signaling mediating outgrowth unknown
    • Single lab
  4. 2008 Medium

    Revealed that NEGR1 controls synapse number in a developmental-stage-dependent manner correlated with subcellular relocalization, indicating context-dependent function.

    Evidence Overexpression in cultured hippocampal neurons with synapse counting and detergent extraction

    PMID:18602091

    Open questions at the time
    • Mechanism linking localization shift to synapse change unresolved
    • Gain-of-function only
  5. 2016 High

    Defined the ADAM10→soluble NEGR1→FGFR2→ERK axis, showing the shed ectodomain acts as a diffusible neurite-promoting ligand.

    Evidence ADAM10 pharmacological inhibition and silencing in primary neurons with rescue by soluble Negr1

    PMID:26793057

    Open questions at the time
    • Direct soluble NEGR1–FGFR2 binding not biochemically isolated
    • Physiological extent of shedding in vivo unquantified
  6. 2016 Medium

    Linked NEGR1 to lipid metabolism by showing it stabilizes NPC2 and limits cholesterol/triglyceride accumulation, extending its role beyond adhesion.

    Evidence Co-IP, protein stability assay, and cholesterol rescue in NEGR1-deficient MEFs

    PMID:27940359

    Open questions at the time
    • Whether NPC2 stabilization underlies neural phenotypes untested
    • Single lab, two methods
  7. 2018 High

    Identified FGFR2 as a direct NEGR1 partner whose plasma-membrane stability NEGR1 sustains, providing the core mechanism for NEGR1 control of cortical neuron migration and spine density.

    Evidence Reciprocal Co-IP, in utero electroporation, ERK/AKT immunoblotting, KO mice, and FGFR2 rescue

    PMID:30059965

    Open questions at the time
    • Molecular basis of NEGR1-dependent FGFR2 stabilization unresolved
    • Stoichiometry of NEGR1–FGFR2 complex unknown
  8. 2019 High

    Established a NEGR1–LIFR–Lcn2 axis regulating adult hippocampal neurogenesis, plasticity, and affective behavior, with Lcn2 sufficient to rescue knockout phenotypes.

    Evidence Co-IP, Negr1 KO mice, LTP/mEPSC recording, AAV-Lcn2 rescue, and BrdU neurogenesis

    PMID:30651602

    Open questions at the time
    • How NEGR1 modulates LIFR signaling mechanistically not defined
    • Relationship to FGFR2 pathway unaddressed
  9. 2019 Medium

    Tied NEGR1 loss to reduced parvalbumin interneurons and gross neuroanatomical defects, anchoring its behavioral roles in inhibitory circuit and structural development.

    Evidence Negr1 KO MRI morphometry, in situ hybridization, parvalbumin immunostaining

    PMID:30932003

    Open questions at the time
    • Cellular mechanism of interneuron loss unresolved
    • Correlative structural readouts
  10. 2021 Medium

    Identified ATP1B1 as a raft-localized NEGR1 partner via its C-terminus, connecting NEGR1 to Na/K-ATPase complexes in membrane microdomains.

    Evidence Yeast two-hybrid, Co-IP, co-localization, and domain mapping

    PMID:32958118

    Open questions at the time
    • Functional consequence of ATP1B1 binding untested
    • No in vivo validation
  11. 2025 High

    Defined a mechanistic role for NEGR1 in palmitoylation-dependent GAD65 trafficking that maintains inhibitory GABA synthesis and hypothalamic GABAergic synapse density.

    Evidence RNAseq, GAD65 plasma membrane biosensor, re-expression rescue, and GABA measurement in Negr1 KO mice

    PMID:39676071

    Open questions at the time
    • Whether NEGR1 directly regulates the palmitoylation machinery unknown
    • Link to FGFR2/LIFR pathways not established
  12. 2025 High

    Showed NEGR1 overexpression in ventral hippocampus drives spine loss and affective deficits and catalogued its synaptic interactome, indicating dose-dependent disruption of synaptic vesicle and myelination programs.

    Evidence AAV overexpression, EM, IP-MS interactome, transcriptomics, and behavioral assays

    PMID:40382479

    Open questions at the time
    • Which interactors mediate the spine-loss phenotype undefined
    • Direct vs indirect transcriptomic effects unresolved
  13. 2025 Medium

    Extended NEGR1 function to peripheral steroidogenesis, showing its loss impairs Leydig-cell testosterone synthesis with testosterone supplementation rescuing behavioral phenotypes.

    Evidence Negr1 KO hormone measurement, steroidogenic enzyme RT-PCR, histology, and testosterone rescue

    PMID:40886916

    Open questions at the time
    • Molecular mechanism in Leydig cells unknown
    • Link to lipid/cholesterol handling not directly tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NEGR1 integrates its multiple receptor partnerships (FGFR2, LIFR, ATP1B1, NPC2) into a unified raft-organizing or signaling function, and how the same molecule produces opposing phenotypes upon loss versus overexpression, remains unresolved.
  • No structure of NEGR1 in complex with any receptor
  • Mechanism reconciling dose-dependent bidirectional synaptic effects unknown
  • Hierarchy among adhesion, FGFR2 stabilization, and lipid functions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0060089 molecular transducer activity 2 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3
Partners
ADAM10ATP1B1FGFR2GAD65LIFRNPC2OBCAM

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 NEGR1 (Kilon) is a GPI-anchored protein belonging to the IgLON immunoglobulin superfamily, containing three C2 domains and six putative glycosylation sites, localized to Triton-insoluble lipid raft membrane fractions in rat brain, with expression restricted to brain tissue. cDNA cloning, phosphatidylinositol-specific phospholipase C solubilization, Western blotting, peptide N-glycosidase F deglycosylation, immunostaining The Journal of biological chemistry High 10075727
2003 Kilon (NEGR1) and OBCAM interact both heterophilically and homophilically, as demonstrated by cross-linker and immunoprecipitation binding analysis; Kilon is localized mainly at postsynaptic sites of dendritic and somatic synapses in adult cerebral cortex and hippocampus, and is present predominantly in the Triton-insoluble fraction. Cross-linker treatment, immunoprecipitation, electron microscopic immunohistochemistry, Western blotting, subcellular fractionation Neuroscience High 12617969
2005 Neurotractin/kilon (NEGR1) promotes neurite outgrowth: in vitro stripe assays showed that neurotractin/kilon attracts hippocampal axons and astroglial neurotractin/kilon promotes neurite outgrowth; expression is upregulated on reactive astrocytes specifically in the denervated outer molecular layer of the dentate gyrus after entorhinal cortex lesion. In vitro stripe assay, entorhinal cortex lesion model, immunohistochemistry, Western blotting Molecular and cellular neurosciences Medium 15946856
2008 Kilon (NEGR1) modulates synapse number in hippocampal neurons in a stage-dependent manner: overexpression decreased dendritic synapse number at early culture stages but increased synapse number at late culture stages, correlating with changes in subcellular localization (axonal/presynaptic early; dendritic postsynaptic late) and detergent solubility. Plasmid-mediated overexpression in cultured hippocampal neurons, synapse counting, immunocytochemistry, detergent extraction Brain research Medium 18602091
2013 NEGR1 controls the development of neurite arborization in vitro and in vivo; identified by cell surface biotinylation proteomics as a differentially expressed membrane protein during neuron maturation. Cell surface biotinylation assay, mass spectrometry, knockdown/overexpression in primary neurons, in vivo analysis Molecular & cellular proteomics : MCP Medium 24382801
2014 NEGR1 is primarily localized to membrane lipid rafts at cell-to-cell contacting areas (GPI-anchored); overexpression of NEGR1 in ovarian cancer cells attenuates oncogenic phenotype, increases cell aggregation and neurite outgrowth, while NEGR1 depletion increases cell migration and invasion. Overexpression and siRNA knockdown, cell aggregation assay, migration/invasion assay, membrane fractionation Journal of Cancer Medium 25057311
2016 NEGR1 is shed from the neuronal membrane by the metalloprotease ADAM10 (ectodomain shedding); soluble/released NEGR1 promotes neurite outgrowth in a FGFR2- and P-ERK1/2-dependent manner. Pharmacological inhibition of ADAM10 impairs neurite tree maturation, which is rescued by treatment with soluble Negr1. Pharmacological ADAM10 inhibition, virus-mediated protein silencing in primary neurons, morphological analysis, rescue with soluble Negr1 treatment Frontiers in molecular neuroscience High 26793057
2016 NEGR1 interacts with NPC2 (Niemann-Pick disease Type C2 protein) and increases its protein stability; NEGR1-deficient mouse embryonic fibroblast cells exhibit increased cholesterol levels and triglyceride contents, and ectopic NEGR1 expression relieves abnormal cholesterol accumulation in endosomal compartments. Co-immunoprecipitation, protein stability assay, cholesterol accumulation assay in NEGR1-deficient MEFs, ectopic expression Biochemical and biophysical research communications Medium 27940359
2018 NEGR1 physically interacts with FGFR2 and modulates FGFR2-dependent ERK and AKT signaling by decreasing FGFR2 degradation from the plasma membrane; downregulation of NEGR1 similarly affects neuronal migration and spine density during mouse cortical development as FGFR2 downregulation; FGFR2 overexpression rescues all defects caused by Negr1 knockdown in vivo. Co-immunoprecipitation, in utero electroporation knockdown/overexpression, spine density analysis, Western blotting for ERK/AKT signaling, Negr1 knockout mice Brain : a journal of neurology High 30059965
2019 NEGR1 interacts with leukemia inhibitory factor receptor (LIFR) and modulates LIF-induced Lcn2 (lipocalin-2) expression in the hippocampus; Negr1-/- mice show decreased adult hippocampal neurogenesis, compromised LTP and mEPSC in the dentate gyrus; heterologous Lcn2 expression in hippocampal DG of negr1-/- mice rescued anxiety/depression-like behaviors and restored neurogenesis and mEPSC frequency. Co-immunoprecipitation (NEGR1-LIFR interaction), Negr1 knockout mice, LTP recording, mEPSC recording, AAV-mediated Lcn2 rescue, BrdU neurogenesis assay Molecular psychiatry High 30651602
2019 Negr1 deficiency results in disrupted neurite sprouting during neuritogenesis, decreased number of parvalbumin-positive inhibitory interneurons in hippocampus, and neuroanatomical abnormalities including ventricle enlargement and reduced volumes of brain, corpus callosum, globus pallidus and hippocampus. Negr1-/- mouse model, in situ hybridization, brain morphological analysis (MRI), parvalbumin immunostaining, neuritogenesis assay Scientific reports Medium 30932003
2021 NEGR1 associates with Na/K-ATPase beta1-subunit (ATP1B1), identified by yeast two-hybrid screening; the two proteins form a stable complex partially co-localizing in membrane lipid rafts; NEGR1 binds ATP1B1 at its C-terminus, away from the alpha subunit binding site. Yeast two-hybrid screening, co-immunoprecipitation, co-localization by immunofluorescence, domain mapping BMB reports Medium 32958118
2022 IgLON4 (NEGR1 alias) is expressed in mouse skeletal muscle, localized to cell membrane at cell-to-cell adhesion sites, promotes myotube alignment and myogenic differentiation, and is linked to lipid raft accumulation during myogenic differentiation. IgLON4 inhibition disrupts myotube alignment. siRNA knockdown, immunofluorescence, CTX muscle injury model, directional myotube analysis, lipid raft staining Cells Medium 36291131
2023 Negr1 (as a GPI-anchored membrane protein and as a soluble form released by metalloprotease cleavage) induces ALK receptor downregulation in neuroblastoma; Negr1-derived peptides halt neuroblastoma progression in vitro and in vivo. Ectopic overexpression in neuroblastoma cells, in vitro growth assay, in vivo xenograft model, Negr1-derived peptide treatment, Western blotting for ALK Pharmaceutics Medium 37765276
2025 NEGR1 promotes palmitoylation-dependent clearance of GAD65 (glutamic acid decarboxylase 65) from the plasma membrane and its targeting to plasma membrane-derived endocytic vesicles; NEGR1 deficiency results in non-synaptic accumulation of GAD65, increased plasma membrane-attached GAD65 at synaptic and extrasynaptic sites, reduced synaptic GABA levels, lower GABAergic synapse densities in the arcuate nucleus, and reduced body weight and blunted food reward responses. RNAseq in NEGR1-deficient mice, GAD65 plasma membrane biosensor, immunofluorescence, re-expression rescue, Negr1-/- mouse model, GABA level measurement Journal of neurochemistry High 39676071
2025 NEGR1 overexpression in the ventral hippocampus (vHIP) of mice leads to dendritic spine loss, synaptic ultrastructure abnormality, working memory impairment, and anxiety/depression-like behaviors; immunoprecipitation-mass spectrometry identified 67 high-confidence NEGR1-interacting proteins enriched in neurotransmitter exocytosis and synaptic vesicle endocytosis; transcriptomic profiling revealed enrichment in myelination-related pathways. Stereotaxic AAV injection for NEGR1 overexpression, behavioral assays, neuronal sparse labeling, transmission electron microscopy, immunoprecipitation-mass spectrometry, transcriptomic profiling, reporter gene assay, EMSA Molecular psychiatry High 40382479
2025 NEGR1 deficiency in mice reduces serum and testicular testosterone levels, downregulates key testosterone-synthesizing enzymes in Leydig cells, causes lipid droplet accumulation in testicular cells, disorganized testicular/epididymal structures, and increased abnormal sperm morphology; testosterone supplementation rescues impaired sexual behaviors and alleviates anxiety/depression-like phenotypes in Negr1-/- mice. Negr1-/- mouse model, hormone measurement, RT-PCR for steroidogenic enzyme expression, histological analysis, testosterone supplementation rescue Journal of lipid research Medium 40886916
2024 AP1AR-DT lncRNA reduces NEGR1 expression by competing for the transcriptional activator NRF1 at the overlapping binding site of the NEGR1 promoter region; overexpression of Negr1 in mPFC neurons of AP1AR-DT overexpressing mice ameliorates depressive and anxiety-like behaviors and normalizes reduced excitatory synaptic transmission. Chromatin immunoprecipitation, reporter gene assay, electrophysiological assays, behavioral tests, NEGR1 overexpression rescue in vivo BMC medicine Medium 39558356
2014 Decreased Negr1 expression in periventricular hypothalamic areas (via AAV-mediated knockdown) leads to increased body weight and food intake; both increased and decreased Negr1 levels lead to reduced locomotor activity and body temperature, indicating a role for hypothalamic Negr1 in energy balance regulation. AAV-mediated in vivo knockdown/overexpression in hypothalamus, body weight measurement, food intake monitoring, locomotor activity and body temperature measurement Physiological reports Medium 25077509
2024 NEGR1 deficiency in mice increases inhibitory inputs to mitral cells in the olfactory bulb, decreases mitral cell excitability, and reduces adult neurogenesis in the subventricular zone (diminished integration of newly generated inhibitory neurons into the olfactory bulb), resulting in aberrant olfactory habituation/dishabituation and impaired affective discrimination. Whole-cell patch clamp electrophysiology, BrdU neurogenesis assay, olfactory behavioral testing, Negr1-/- mouse model Biological psychiatry global open science Medium 39170714

Source papers

Stage 0 corpus · 76 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1985 Products of nitrogen regulatory genes ntrA and ntrC of enteric bacteria activate glnA transcription in vitro: evidence that the ntrA product is a sigma factor. Proceedings of the National Academy of Sciences of the United States of America 327 2999766
1987 Rhizobium meliloti ntrA (rpoN) gene is required for diverse metabolic functions. Journal of bacteriology 198 3034856
1999 Characterization of a novel rat brain glycosylphosphatidylinositol-anchored protein (Kilon), a member of the IgLON cell adhesion molecule family. The Journal of biological chemistry 110 10075727
1987 Involvement of the ntrA gene product in the anaerobic metabolism of Escherichia coli. Molecular & general genetics : MGG 100 3323848
1985 The nucleotide sequence of the nitrogen-regulation gene ntrA of Klebsiella pneumoniae and comparison with conserved features in bacterial RNA polymerase sigma factors. Nucleic acids research 100 2999700
1989 The DNA sequence of the Rhodobacter capsulatus ntrA, ntrB and ntrC gene analogues required for nitrogen fixation. Molecular & general genetics : MGG 83 2710108
1983 Nitrogen control of the nif regulon in Klebsiella pneumoniae: involvement of the ntrA gene and analogies between ntrC and nifA. The EMBO journal 82 11894906
2019 Negr1 controls adult hippocampal neurogenesis and affective behaviors. Molecular psychiatry 73 30651602
1987 The nucleotide sequence of the sigma factor gene ntrA (rpoN) of Azotobacter vinelandii: analysis of conserved sequences in NtrA proteins. Molecular & general genetics : MGG 69 3481423
2018 NEGR1 and FGFR2 cooperatively regulate cortical development and core behaviours related to autism disorders in mice. Brain : a journal of neurology 65 30059965
2005 Neurotractin/kilon promotes neurite outgrowth and is expressed on reactive astrocytes after entorhinal cortex lesion. Molecular and cellular neurosciences 65 15946856
2003 Biochemical and ultrastructural analyses of IgLON cell adhesion molecules, Kilon and OBCAM in the rat brain. Neuroscience 63 12617969
2019 Neural cell adhesion molecule Negr1 deficiency in mouse results in structural brain endophenotypes and behavioral deviations related to psychiatric disorders. Scientific reports 59 30932003
2008 IgLON cell adhesion molecule Kilon is a crucial modulator for synapse number in hippocampal neurons. Brain research 59 18602091
2018 Neuronal Growth and Behavioral Alterations in Mice Deficient for the Psychiatric Disease-Associated Negr1 Gene. Frontiers in molecular neuroscience 54 29479305
2012 Nutritional state affects the expression of the obesity-associated genes Etv5, Faim2, Fto, and Negr1. Obesity (Silver Spring, Md.) 54 22627920
2016 The IgLON Family Member Negr1 Promotes Neuronal Arborization Acting as Soluble Factor via FGFR2. Frontiers in molecular neuroscience 53 26793057
2013 A cell surface biotinylation assay to reveal membrane-associated neuronal cues: Negr1 regulates dendritic arborization. Molecular & cellular proteomics : MCP 53 24382801
2014 Newly Identified Cancer-Associated Role of Human Neuronal Growth Regulator 1 (NEGR1). Journal of Cancer 49 25057311
1990 Characterization of divergent NtrA-dependent promoters in the anaerobically expressed gene cluster coding for hydrogenase 3 components of Escherichia coli. Molecular microbiology 48 2181234
2014 The obesity-associated gene Negr1 regulates aspects of energy balance in rat hypothalamic areas. Physiological reports 43 25077509
2000 prpR, ntrA, and ihf functions are required for expression of the prpBCDE operon, encoding enzymes that catabolize propionate in Salmonella enterica serovar typhimurium LT2. Journal of bacteriology 42 10648513
1989 Identification of a gene linked to Rhizobium meliloti ntrA whose product is homologous to a family to ATP-binding proteins. Journal of bacteriology 41 2703463
1985 Studies on the regulation and function of the Klebsiella pneumoniae ntrA gene. Gene 40 3899862
2008 Accumulation of flavonoids in an ntra ntrb mutant leads to tolerance to UV-C. Molecular plant 39 19825611
1989 Cloning and sequence analysis of the ntrA (rpoN) gene of Pseudomonas putida. Gene 39 2695395
2016 The new obesity-associated protein, neuronal growth regulator 1 (NEGR1), is implicated in Niemann-Pick disease Type C (NPC2)-mediated cholesterol trafficking. Biochemical and biophysical research communications 36 27940359
2014 Obesity gene NEGR1 associated with white matter integrity in healthy young adults. NeuroImage 34 25072390
2011 Aberrations of NEGR1 on 1p31 and MYEOV on 11q13 in neuroblastoma. Cancer science 34 21624008
2019 Integrating genome-wide association study and expression quantitative trait loci data identifies NEGR1 as a causal risk gene of major depression disorder. Journal of affective disorders 30 32090785
1993 Azorhizobium caulinodans nitrogen fixation (nif/fix) gene regulation: mutagenesis of the nifA -24/-12 promoter element, characterization of a ntrA(rpoN) gene, and derivation of a model. Molecular plant-microbe interactions : MPMI 30 8471796
2000 Expression of the IgLON cell adhesion molecules Kilon and OBCAM in hypothalamic magnocellular neurons. The Journal of comparative neurology 29 10888740
2014 Impact of NEGR1 genetic variability on psychological traits of patients with eating disorders. The pharmacogenomics journal 25 25245582
1990 Complementation of Escherichia coli sigma 54 (NtrA)-dependent formate hydrogenlyase activity by a cloned Thiobacillus ferrooxidans ntrA gene. Journal of bacteriology 25 2198257
2020 Depression-Associated Gene Negr1-Fgfr2 Pathway Is Altered by Antidepressant Treatment. Cells 23 32751911
2020 Circ_HECW2 functions as a miR-30e-5p sponge to regulate LPS-induced endothelial-mesenchymal transition by mediating NEGR1 expression. Brain research 23 32916175
2014 Common variants in BDNF, FAIM2, FTO, MC4R, NEGR1, and SH2B1 show association with obesity-related variables in Spanish Roma population. American journal of human biology : the official journal of the Human Biology Council 22 24948161
2024 miR-122/NEGR1 axis contributes colorectal cancer liver metastasis by PI3K/AKT pathway and macrophage modulation. Journal of translational medicine 19 39587606
1991 Transcriptional regulation of cytochrome d in nitrogen-fixing Azotobacter vinelandii. Evidence that up-regulation during N2 fixation is independent of nifA but dependent on ntrA. The Journal of biological chemistry 19 1660468
2015 Involvement of reductases IruO and NtrA in iron acquisition by Staphylococcus aureus. Molecular microbiology 16 25777658
1992 Transcription of the Azospirillum brasilense nifH gene is positively regulated by NifA and NtrA and is negatively controlled by the cellular nitrogen status. Molecular & general genetics : MGG 16 1557035
1991 NifA-NtrA regulatory system activates transcription of nfe, a gene locus involved in nodulation competitiveness of Rhizobium meliloti. Archives of microbiology 16 1953295
2021 High-Fat Diet Induces Pre-Diabetes and Distinct Sex-Specific Metabolic Alterations in Negr1-Deficient Mice. Biomedicines 15 34572334
2021 CircDLGAP4 overexpression relieves oxygen-glucose deprivation-induced neuronal injury by elevating NEGR1 through sponging miR-503-3p. Journal of molecular histology 15 34739656
2020 SNHG12 inhibits oxygen‑glucose deprivation‑induced neuronal apoptosis via the miR‑181a‑5p/NEGR1 axis. Molecular medicine reports 15 33000228
2019 MicroRNA-25-5p counteracts oxidized LDL-induced pathological changes by targeting neuronal growth regulator 1 (NEGR1) in human brain micro-vessel endothelial cells. Biochimie 15 31365884
1986 Isolation of ntrA-like mutants of Azotobacter vinelandii. Journal of bacteriology 15 3009406
2022 IgLON4 Regulates Myogenesis via Promoting Cell Adhesion and Maintaining Myotube Orientation. Cells 14 36291131
2000 IG-molecule Kilon shows differential expression pattern from LAMP in the developing and adult rat hippocampus. Hippocampus 14 11153709
2019 Placental NEGR1 DNA methylation is associated with BMI and neurodevelopment in preschool-age children. Epigenetics 12 31510847
2022 Depression-Associated Negr1 Gene-Deficiency Induces Alterations in the Monoaminergic Neurotransmission Enhancing Time-Dependent Sensitization to Amphetamine in Male Mice. Brain sciences 11 36552158
1992 The ntrA gene of Agrobacterium tumefaciens: identification, cloning, and phenotype of a site-directed mutant. Journal of bacteriology 11 1556090
2021 Na/K-ATPase beta1-subunit associates with neuronal growth regulator 1 (NEGR1) to participate in intercellular interactions. BMB reports 9 32958118
2025 Neuronal growth regulator 1 (NEGR1) promotes the synaptic targeting of glutamic acid decarboxylase 65 (GAD65). Journal of neurochemistry 8 39676071
2025 Elevated NEGR1 in brain induces anxiety or depression-like phenotypes and synaptic dysfunction. Molecular psychiatry 8 40382479
2022 miR-576-5p Facilitates Aggressive Cell Behaviors in Colon Adenocarcinoma via Targeting NEGR1. Critical reviews in eukaryotic gene expression 8 36004693
2020 Depression in multiple sclerosis patients associated with risk variant near NEGR1. Multiple sclerosis and related disorders 7 33296963
2025 Akkermansia muciniphila reverses neuronal atrophy in Negr1 knockout mice with depression-like phenotypes. Gut microbes 6 40388597
2020 1p31.1 microdeletion including only NEGR1 gene in two patients. European journal of medical genetics 6 32209393
2024 Gain of bipolar disorder-related lncRNA AP1AR-DT in mice induces depressive and anxiety-like behaviors by reducing Negr1-mediated excitatory synaptic transmission. BMC medicine 5 39558356
2024 The Risk Genes for Neuropsychiatric Disorders negr1 and opcml Are Expressed throughout Zebrafish Brain Development. Genes 4 38540422
2023 Negr1-Derived Peptides Trigger ALK Degradation and Halt Neuroblastoma Progression In Vitro and In Vivo. Pharmaceutics 4 37765276
2022 LncRNA MIAT Upregulates NEGR1 by Competing for miR-150-5p as a Competitive Endogenous RNA in SCIRI Rats. International journal of genomics 4 36620092
2008 Characterization of Brucella abortus sigma factor sigma54 (rpoN): genetic complementation of Sinorhizobium meliloti ntrA mutant. Microbial pathogenesis 4 18926896
2024 NEGR1 Modulates Mouse Affective Discrimination by Regulating Adult Olfactory Neurogenesis. Biological psychiatry global open science 3 39170714
2018 In silico approach to identify non-synonymous SNPs with highest predicted deleterious effect on protein function in human obesity related gene, neuronal growth regulator 1 (NEGR1). 3 Biotech 3 30402368
2025 NEGR1 deficiency disrupts lipid metabolism and steroidogenesis in Leydig cells, linking testosterone to behavior. Journal of lipid research 2 40886916
2016 Supporting data for characterization of non-coding RNAs associated with the Neuronal growth regulator 1 (NEGR1) adhesion protein. Data in brief 2 26977442
2025 Peripheral gene dysregulation in Negr1-deficient mice: insights into possible links with affective behavior. Frontiers in molecular neuroscience 1 40698360
2025 Negr1 Deficiency Modulates Sex-Specific Neurobehavioral Adaptations to Social Isolation. Brain sciences 1 41440084
1992 The role of ntrA in the anaerobic metabolism of Salmonella typhimurium. FEMS microbiology letters 1 1537537
2026 Negr1 deficiency alters glutamate signalling and kynurenine pathway in a mouse model of psychiatric disorders. Scientific reports 0 41545566
2026 Sex-specific changes in the hippocampal proteome of Negr1-/- mice: insight into the mechanisms of neuropsychiatric disorders. Biology of sex differences 0 41888955
2026 Major Depression-Associated NEGR1 Gene is Modulated in Stress-Susceptible Male Mice. Frontiers in bioscience (Landmark edition) 0 41914288
2025 Interplay between depressive symptoms and Alzheimer's disease dementia: unraveling the potential roles of ADAM10 and Negr1. Neuroscience 0 40812721
2024 The Association between Obesity Susceptibility and Polymorphisms of MC4R, SH2B1, and NEGR1 in Tibetans. Genetic testing and molecular biomarkers 0 39034913

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