Affinage

NIN

Ninein · UniProt Q8N4C6

Length
2090 aa
Mass
243.2 kDa
Annotated
2026-06-10
90 papers in source corpus 4 papers cited in narrative 4 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 1/2 claims corpus-supported (50%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NIN (Ninein) is a centrosomal protein implicated in cell division, oncogenesis, and skeletal and cortical development. Its predicted oligomerization domains underlie its capacity to constitutively activate fused kinases: a t(5;14)(q33;q24) translocation generates a NIN-PDGFRB fusion that drives an imatinib-responsive myeloproliferative disorder through NIN-mediated dimerization and constitutive PDGFRB kinase signaling (PMID:15087377). Independent of this rearrangement, NIN pre-mRNA is a direct substrate of the splicing factor QKI, which binds it and promotes inclusion of exon 18 to generate an oncogenic isoform that sustains breast cancer cell proliferation, migration, and invasion by engaging the CDK2/Cyclin A axis, with depletion of the exon-18-included isoform inducing S-phase arrest and inhibiting tumor growth in vivo (PMID:41135748). Beyond these oncogenic and splicing-regulated mechanisms, the structural and biochemical basis of NIN's centrosomal function has not been directly characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2004 Medium

    Established NIN as an oncogenic fusion partner whose oligomerization domains can constitutively activate a receptor tyrosine kinase, explaining why a centrosomal protein contributes to myeloproliferative disease.

    Evidence FISH breakpoint mapping and RT-PCR detection of NIN-PDGFRB fusion mRNA in a chronic myeloproliferative disorder patient, with clinical imatinib response

    PMID:15087377

    Open questions at the time
    • NIN oligomerization was inferred computationally, not demonstrated biochemically
    • single case report without reconstitution of the fusion's kinase activity
    • wild-type NIN's normal centrosomal mechanism not addressed
  2. 2012 Low

    Linked NIN to the evolutionary expansion of cortical neuron number by associating positive selection on NIN with neurogenic radial glial cell divisions and brain size.

    Evidence Molecular evolutionary analysis (dN/dS across primate lineages) correlated with neonatal brain size in catarrhines

    PMID:22937743

    Open questions at the time
    • comparative analysis only; no direct cellular experiment on NIN function in RGC divisions
    • mechanistic role in neurogenic divisions cited from prior literature, not tested here
    • molecular pathway connecting NIN to division asymmetry undefined
  3. 2013 Low

    Connected NIN loss-of-function to human skeletal dysplasia, implicating centrosomal/ciliogenic function in skeletal development.

    Evidence Homozygosity mapping, whole-exome sequencing, and cosegregation in a consanguineous family with a SEMDJL2-like phenotype, with population control screening

    PMID:23665482

    Open questions at the time
    • no biochemical or cell biological assay on the mutant protein performed
    • functional relationship with KIF22 and centrosomal function inferred from literature
    • causal mechanism linking NIN mutation to skeletal phenotype not established
  4. 2025 Medium

    Identified NIN pre-mRNA as a direct QKI splicing target, defining an exon-18-included isoform as an oncogenic driver acting through the CDK2/Cyclin A cell-cycle axis.

    Evidence eCLIP for direct RNA binding, isoform-specific knockdown with proliferation/migration/invasion assays, flow cytometry cell-cycle analysis, CDK2/Cyclin A western blot, and xenograft tumor model in breast cancer

    PMID:41135748

    Open questions at the time
    • single-lab study without independent replication
    • molecular function of the exon-18-included isoform protein not defined
    • mechanism linking the isoform to CDK2/Cyclin A regulation not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The direct biochemical and structural basis of NIN's centrosomal activity, and how it mechanistically couples to neurogenic division, skeletal development, and cell-cycle control, remains unresolved.
  • no structural model of NIN or its oligomerization domains
  • no direct demonstration of NIN's molecular activity at the centrosome
  • mechanism connecting NIN isoform to CDK2/Cyclin A regulation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Partners
PDGFRBQKI

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 NIN (Ninein) was identified as a centrosomal protein with CEP110-like function. It was found fused to PDGFRB via a t(5;14)(q33;q24) chromosomal translocation in a patient with chronic myeloproliferative disorder with eosinophilia, producing the oncogenic NIN-PDGFRB fusion. The NIN gene was selected as a candidate partner based on the presence of predicted oligomerization domains. Treatment with imatinib produced hematological and cytogenetic remission, consistent with constitutive PDGFRB kinase activation driven by NIN-mediated oligomerization. Fluorescence in situ hybridization (FISH) to map breakpoints, reverse transcription-PCR to detect NIN-PDGFRB fusion mRNA, candidate gene selection based on oligomerization domain prediction, clinical imatinib response Cancer research Medium 15087377
2012 NIN (Ninein) is necessary for maintaining asymmetric, neurogenic divisions of radial glial cells (RGCs). Positive selection on NIN was detected during anthropoid primate evolution, and selection on NIN was significantly associated with neonatal brain size in catarrhines, implicating NIN in the evolution of cortical neuron number through neurogenic RGC divisions. Molecular evolutionary analysis (dN/dS ratios across primate lineages), correlation of selection signatures with neural phenotypes (neonatal brain size, neuron number estimates) Genes, brain, and behavior Low 22937743
2013 Homozygous missense mutations in NIN (Ninein) were identified in a consanguineous family with a spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL2)-like phenotype. The NIN protein showed a functional relationship with KIF22 and other proteins associated with chromosome congression/movement, centrosomal function, and ciliogenesis, supporting a fundamental role for Ninein in skeletal development. Evidence included cosegregation of the variant with disease phenotype, absence in 500 healthy controls and 1000-genomes database, and comparison with previously identified compound heterozygous NIN mutations in microcephalic primordial dwarfism. Homozygosity mapping, whole-exome sequencing, cosegregation analysis, population control screening, functional relationship inference from known NIN interactors Matrix biology : journal of the International Society for Matrix Biology Low 23665482
2025 QKI splicing factor directly binds NIN pre-mRNA and promotes inclusion of exon 18, generating an oncogenic exon-18-included NIN isoform. Depletion of the exon-18-included NIN isoform suppressed proliferation, migration, and invasion of breast cancer cells, induced S-phase arrest via dysregulation of the CDK2/Cyclin A axis, and significantly inhibited tumor growth in vivo. Multi-omics TCGA analysis, RNA binding protein eCLIP, functional knockdown experiments (cell proliferation, migration, invasion assays), flow cytometry cell cycle analysis, CDK2/Cyclin A western blot, in vivo xenograft tumor model Cellular signalling Medium 41135748

Source papers

Stage 0 corpus · 90 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Medicago truncatula NIN is essential for rhizobial-independent nodule organogenesis induced by autoactive calcium/calmodulin-dependent protein kinase. Plant physiology 310 17369436
2022 NIN-like protein 7 transcription factor is a plant nitrate sensor. Science (New York, N.Y.) 200 36137053
2018 A NIN-LIKE PROTEIN mediates nitrate-induced control of root nodule symbiosis in Lotus japonicus. Nature communications 145 29403008
2015 The NIN Transcription Factor Coordinates Diverse Nodulation Programs in Different Tissues of the Medicago truncatula Root. The Plant cell 138 26672071
2018 NIN interacts with NLPs to mediate nitrate inhibition of nodulation in Medicago truncatula. Nature plants 131 30297831
2003 The Sym35 gene required for root nodule development in pea is an ortholog of Nin from Lotus japonicus. Plant physiology 116 12644653
2019 A Remote cis-Regulatory Region Is Required for NIN Expression in the Pericycle to Initiate Nodule Primordium Formation in Medicago truncatula. The Plant cell 106 30610167
2021 NIN-like protein transcription factors regulate leghemoglobin genes in legume nodules. Science (New York, N.Y.) 102 34709882
2019 NIN Acts as a Network Hub Controlling a Growth Module Required for Rhizobial Infection. Plant physiology 101 30710053
2020 The NIN transcription factor coordinates CEP and CLE signaling peptides that regulate nodulation antagonistically. Nature communications 95 32576831
2020 Rice NIN-LIKE PROTEIN 4 plays a pivotal role in nitrogen use efficiency. Plant biotechnology journal 91 32876985
2020 Rice NIN-LIKE PROTEIN 1 rapidly responds to nitrogen deficiency and improves yield and nitrogen use efficiency. Journal of experimental botany 86 32585013
2021 Different DNA-binding specificities of NLP and NIN transcription factors underlie nitrate-induced control of root nodulation. The Plant cell 78 33826745
2013 MicroRNA-326 functions as a tumor suppressor in glioma by targeting the Nin one binding protein (NOB1). PloS one 75 23869222
2019 Evolutionary analyses of NIN-like proteins in plants and their roles in nitrate signaling. Cellular and molecular life sciences : CMLS 67 31161283
2014 Downregulated miR-646 in clear cell renal carcinoma correlated with tumour metastasis by targeting the nin one binding protein (NOB1). British journal of cancer 65 25010867
2009 Fatty acid desaturation index correlates with body mass and adiposity indices of obesity in Wistar NIN obese mutant rat strains WNIN/Ob and WNIN/GR-Ob. Nutrition & metabolism 58 19519902
2022 Rice NIN-LIKE PROTEIN 3 modulates nitrogen use efficiency and grain yield under nitrate-sufficient conditions. Plant, cell & environment 57 35150141
2020 The NIN-like protein 5 (ZmNLP5) transcription factor is involved in modulating the nitrogen response in maize. The Plant journal : for cell and molecular biology 57 31793100
2015 The Casuarina NIN gene is transcriptionally activated throughout Frankia root infection as well as in response to bacterial diffusible signals. The New phytologist 57 26096779
2020 Evolution of NIN and NIN-like Genes in Relation to Nodule Symbiosis. Genes 56 32664480
2015 MicroRNA-326 functions as a tumor suppressor in colorectal cancer by targeting the nin one binding protein. Oncology reports 55 25760058
2013 The evolutionary events necessary for the emergence of symbiotic nitrogen fixation in legumes may involve a loss of nitrate responsiveness of the NIN transcription factor. Plant signaling & behavior 52 24270631
2004 NIN, a gene encoding a CEP110-like centrosomal protein, is fused to PDGFRB in a patient with a t(5;14)(q33;q24) and an imatinib-responsive myeloproliferative disorder. Cancer research 51 15087377
2022 Asymmetric redundancy of soybean Nodule Inception (NIN) genes in root nodule symbiosis. Plant physiology 46 34633461
2022 Nitrate transport via NRT2.1 mediates NIN-LIKE PROTEIN-dependent suppression of root nodulation in Lotus japonicus. The Plant cell 45 35146519
2021 NIN is essential for development of symbiosomes, suppression of defence and premature senescence in Medicago truncatula nodules. The New phytologist 45 33471433
2023 The small peptide CEP1 and the NIN-like protein NLP1 regulate NRT2.1 to mediate root nodule formation across nitrate concentrations. The Plant cell 44 36440970
2020 Mutant analysis in the nonlegume Parasponia andersonii identifies NIN and NF-YA1 transcription factors as a core genetic network in nitrogen-fixing nodule symbioses. The New phytologist 37 31863481
2016 The Transcription Factor NIN-LIKE PROTEIN7 Controls Border-Like Cell Release. Plant physiology 33 27221617
1988 Design, structure-activity, and molecular modeling studies of potent renin inhibitory peptides having N-terminal Nin-For-Trp (Ftr): angiotensinogen congeners modified by P1-P1' Phe-Phe, Sta, Leu psi[CH(OH)CH2]Val or leu psi[CH2NH]Val substitutions. Journal of medicinal chemistry 30 3275777
2011 Effect of vitamin supplementation on cisplatin-induced intestinal epithelial cell apoptosis in Wistar/NIN rats. Nutrition (Burbank, Los Angeles County, Calif.) 28 22189195
2018 Actinorhizal Signaling Molecules: Frankia Root Hair Deforming Factor Shares Properties With NIN Inducing Factor. Frontiers in plant science 27 30405656
2023 Interplay between NIN-LIKE PROTEINs 6 and 7 in nitrate signaling. Plant physiology 25 37073492
2020 Transcriptional regulation of NIN expression by IPN2 is required for root nodule symbiosis in Lotus japonicus. The New phytologist 24 32187696
2020 NIN-like protein 7 promotes nitrate-mediated lateral root development by activating transcription of TRYPTOPHAN AMINOTRANSFERASE RELATED 2. Plant science : an international journal of experimental plant biology 24 33487355
2017 Dissection of broad-spectrum resistance of the Thai rice variety Jao Hom Nin conferred by two resistance genes against rice blast. Rice (New York, N.Y.) 23 28493203
2011 Downregulation of NIN/RPN12 binding protein inhibit the growth of human hepatocellular carcinoma cells. Molecular biology reports 23 21573803
2024 NIN-LIKE PROTEIN3.2 inhibits repressor Aux/IAA14 expression and enhances root biomass in maize seedlings under low nitrogen. The Plant cell 22 38917216
2013 Expression and clinical significance of the nin one binding protein and p38 MAPK in prostate carcinoma. International journal of clinical and experimental pathology 22 24228091
2019 ERN1 and CYCLOPS coordinately activate NIN signaling to promote infection thread formation in Lotus japonicus. Journal of plant research 21 31313020
2014 Weak pulling forces exerted on Nin-orientated transmembrane segments during co-translational insertion into the inner membrane of Escherichia coli. FEBS letters 21 24726730
2016 MiR-192 suppresses the tumorigenicity of prostate cancer cells by targeting and inhibiting nin one binding protein. International journal of molecular medicine 19 26743688
2013 Identification of a Ninein (NIN) mutation in a family with spondyloepimetaphyseal dysplasia with joint laxity (leptodactylic type)-like phenotype. Matrix biology : journal of the International Society for Matrix Biology 19 23665482
2022 The CYCLOPS Response Element in the NIN Promoter Is Important but Not Essential for Infection Thread Formation During Lotus japonicus-Rhizobia Symbiosis. Molecular plant-microbe interactions : MPMI 17 35343248
2021 Genome-wide survey and expression analysis of NIN-like Protein (NLP) genes reveals its potential roles in the response to nitrate signaling in tomato. BMC plant biology 17 34301191
1982 Effect of Nin-formylation of the tryptophan residue on gastrin (HG-13) binding and on gastric acid secretion. European journal of pharmacology 17 6277651
2012 Positive selection on NIN, a gene involved in neurogenesis, and primate brain evolution. Genes, brain, and behavior 16 22937743
2005 Chronic low intake of protein or vitamins increases the intestinal epithelial cell apoptosis in Wistar/NIN rats. Nutrition (Burbank, Los Angeles County, Calif.) 16 16039830
2023 Conserved and unique functions of NIN-like proteins in nitrate sensing and signaling. Plant science : an international journal of experimental plant biology 15 37633494
1988 Analysis of transcription termination signals in the nin region of bacteriophage lambda: the roc deletion. Journal of bacteriology 15 2972695
2022 The NIN-Like Protein OsNLP2 Negatively Regulates Ferroptotic Cell Death and Immune Responses to Magnaporthe oryzae in Rice. Antioxidants (Basel, Switzerland) 14 36139868
2019 CLE-HAR1 Systemic Signaling and NIN-Mediated Local Signaling Suppress the Increased Rhizobial Infection in the daphne Mutant of Lotus japonicus. Molecular plant-microbe interactions : MPMI 14 31880983
2024 Genome-wide identification and expression analysis of NIN-like protein (NLP) genes: Exploring their potential roles in nitrate response in tea plant (Camellia sinensis). Plant physiology and biochemistry : PPB 13 38199025
2024 NIN-like proteins (NLPs) as crucial nitrate sensors: an overview of their roles in nitrogen signaling, symbiosis, abiotic stress, and beyond. Physiology and molecular biology of plants : an international journal of functional plant biology 13 39100871
2021 NIN-like protein7 and PROTEOLYSIS6 functional interaction enhances tolerance to sucrose, ABA, and submergence. Plant physiology 13 34618055
2021 Functional analyses unveil the involvement of moso bamboo (Phyllostachys edulis) group I and II NIN-LIKE PROTEINS in nitrate signaling regulation. Plant science : an international journal of experimental plant biology 11 33775367
2021 Three Common Symbiotic ABC Subfamily B Transporters in Medicago truncatula Are Regulated by a NIN-Independent Branch of the Symbiosis Signaling Pathway. Molecular plant-microbe interactions : MPMI 11 33779265
2016 NIN Is Involved in the Regulation of Arbuscular Mycorrhizal Symbiosis. Frontiers in plant science 11 27899928
2017 Heteroborospherene clusters Nin ∈ B40 (n = 1-4) and heteroborophene monolayers Ni2 ∈ B14 with planar heptacoordinate transition-metal centers in η7-B7 heptagons. Scientific reports 10 28720806
2022 NiN-Passivated NiO Hole-Transport Layer Improves Halide Perovskite-Based Solar Cell. ACS applied materials & interfaces 9 36226899
2021 Phylogenetic and Structural Analysis of NIN-Like Proteins With a Type I/II PB1 Domain That Regulates Oligomerization for Nitrate Response. Frontiers in plant science 9 34135927
2000 Effects of qian-kun-nin, a Chinese herbal medicine formulation, on HIV positive subjects: a pilot study. The American journal of Chinese medicine 9 11154043
2016 The Topology of the l-Arginine Exporter ArgO Conforms to an Nin-Cout Configuration in Escherichia coli: Requirement for the Cytoplasmic N-Terminal Domain, Functional Helical Interactions, and an Aspartate Pair for ArgO Function. Journal of bacteriology 8 27645388
2022 Overexpression of microRNA-107 suppressed proliferation, migration, invasion, and the PI3K/Akt signaling pathway and induced apoptosis by targeting Nin one binding (NOB1) protein in a hypopharyngeal squamous cell carcinoma cell line (FaDu). Bioengineered 7 35294329
2014 Evaluation of NIN/RPN12 binding protein inhibits proliferation and growth in human renal cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 6 25420906
2023 Identification and expression characteristics of NLP (NIN-like protein) gene family in pepper (Capsicum annuum L.). Molecular biology reports 4 37358766
2020 Transcriptome Comparison of Defense Responses in the Rice Variety 'Jao Hom Nin' Regarding Two Blast Resistant Genes, Pish and Pik. Plants (Basel, Switzerland) 4 32485961
2001 Qian-Kun-Nin, a Chinese herbal medicine formulation, attenuates mitochondrial oxidant stress in cardiomyocytes. Journal of ethnopharmacology 4 11137349
2017 Further insights into the role of NIN-LIKE PROTEIN 7 (NLP7) in root cap cell release. Plant signaling & behavior 3 29215953
2025 Distinct domain regions of NIN and NLP1 mediate symbiotic and nitrate signalling in Medicago truncatula. Journal of experimental botany 2 39905670
2025 GRAS51 promotes legume symbiotic nitrogen fixation and salt tolerance of nodulation by directly regulating NIN expression. Plant physiology 2 41213871
2026 The root nodule symbiosis regulator NIN exhibits broad DNA binding specificity conferred by an NLP-inherited motif. Science advances 1 41616063
2025 The auxin phenylacetic acid induces NIN expression in the actinorhizal plant Datisca glomerata, whereas cytokinin acts antagonistically. PloS one 1 39899489
2025 NiN4/FeN4 dual sites engineered by Fe5 clusters on porous flexible carbon fibers for promoting oxygen reduction and evolution. Journal of colloid and interface science 1 40252579
2025 Genome-wide identification of the apple NLP (NIN-like proteins) family and their potential role under abiotic stress. 3 Biotech 1 40521217
2025 Unlocking Efficient Direct Charge Transfer of Ni-N Bridge 2D N-ZnIn2S4/Ni Single-Atom Photocatalysts for Hydrogen Evolution. ACS applied materials & interfaces 1 40823995
2025 Identification and expression characteristics of NIN-like protein (NLP) gene family in cucumber plant (Cucumis sativus L.). BMC plant biology 1 40885889
2024 The Satellite DNA PcH-Sat, Isolated and Characterized in the Limpet Patella caerulea (Mollusca, Gastropoda), Suggests the Origin from a Nin-SINE Transposable Element. Genes 1 38790169
2023 Local compressive strain regulation of atomically dispersed NiN4 sites for enhancing CO2 electroreduction to CO. Nanoscale 1 37727997
2026 Ancestral functionality and symbiotic refinement of NIN in root nodule symbiosis. Nature communications 0 41942423
2026 MaWRKY76 enhances symbiotic nodulation and salt tolerance of nodulation by activating NIN in Melilotus albus. Journal of genetics and genomics = Yi chuan xue bao 0 42251962
2025 Natural Variation in NIN-LIKE PROTEIN 4 Associated With Spike-Response to Nitrogen in Barley. Plant, cell & environment 0 40159793
2025 Expanding the Clinical Phenotype Associated with the NIN Gene; Report of a Patient with Short Stature, Microcephaly and Hearing Loss. Archives of Iranian medicine 0 40751525
2025 Multi-omics reveals that QKI-mediated NIN exon 18 splicing drives breast cancer cell progression. Cellular signalling 0 41135748
2025 RSD-mediated suppression of NIN and NLP2 transcription is crucial for symbiotic nitrogen fixation. The New phytologist 0 41174857
2025 Genome-Wide Identification and Expression Analysis of the NIN-LIKE Protein (NLP) Gene Family in Salvia Miltiorrhiza. Biochemical genetics 0 41236691
2025 NIN-like protein 2 regulation of nitrite reductase mediates vacuole integrity in Medicago truncatula nodules under high nitrate. Plant physiology 0 41269885
2014 Simplified ZrTiO x -based RRAM cell structure with rectifying characteristics by integrating Ni/n + -Si diode. Nanoscale research letters 0 24936165
1990 [Clinical and experimental study of wei-nin granules in the treatment of chronic superficial gastritis]. Zhong xi yi jie he za zhi = Chinese journal of modern developments in traditional medicine 0 2397540

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