Details for: NAB2

Gene ID: 4665

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: NAB2

Ensembl ID: ENSG00000166886

Description: NGFI-A binding protein 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • progenitor cell CL0011026
    CSI 5.44
    rCSI 11.57%
    PRS 95.39
  • epithelial cell of lower respiratory tract CL0002632
    CSI 4.58
    rCSI 3.55%
    PRS 99.03
  • epithelial cell of lung CL0000082
    CSI 4.4
    rCSI 3.65%
    PRS 98.75
  • interneuron CL0000099
    CSI 3.84
    rCSI 7.71%
    PRS 96.31
  • neural crest cell CL0011012
    CSI 3.5
    rCSI 2.77%
    PRS 96.69
  • fibroblast of lung CL0002553
    CSI 3.49
    rCSI 3.25%
    PRS 98.88
  • interstitial cell of Cajal CL0002088
    CSI 3.41
    rCSI 4.34%
    PRS 99.22
  • mesodermal cell CL0000222
    CSI 3.28
    rCSI 3.93%
    PRS 98.54
  • keratinocyte CL0000312
    CSI 2.88
    rCSI 2.42%
    PRS 97.33
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.87
    rCSI 6.43%
    PRS 94.2
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.58
    rCSI 3.21%
    PRS 93.16
  • enteric smooth muscle cell CL0002504
    CSI 2.43
    rCSI 3.47%
    PRS 98.56
  • enteroendocrine cell CL0000164
    CSI 2.29
    rCSI 3.13%
    PRS 96.9
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.07
    rCSI 2.65%
    PRS 96.99
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.06
    rCSI 2.66%
    PRS 94.72
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.96
    rCSI 3.45%
    PRS 94.13
  • mesenchymal cell CL0008019
    CSI 1.18
    rCSI 3.01%
    PRS 97.3
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.07
    rCSI 2.59%
    PRS 92.8
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.97
    rCSI 3.04%
    PRS 94.44

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary NGFI-A binding protein 2 ([NAB2](/details-gene/4665)) is a protein-coding gene located on chromosome 12q13.3. It functions as a transcriptional coregulator, specifically as a corepressor, by binding to other proteins in the [nucleus](/details-link/GO:0005634). Its expression profile suggests a broad and critical role in development and tissue homeostasis, with particularly high significance in [progenitor cells](/details-cell/CL0011026), various epithelial cells of the lung, and multiple subtypes of neurons. This aligns with its involvement in fundamental biological processes such as [nervous system development](/details-link/R-HSA-9675108) and the regulation of transcription. The gene is also associated with a clinical phenotype documented in OMIM ([602381](https://omim.org/entry/602381)). ## Cellular Roles and Expression Landscape The expression pattern of [NAB2](/details-gene/4665) indicates its importance across multiple cellular lineages, pointing to a foundational role in differentiation and cell fate maintenance. **Overall**, the gene shows its highest significance in [progenitor cells](/details-cell/CL0011026) (CSI: 5.44), suggesting it may function as a key regulator in developmental plasticity and lineage commitment. This is further supported by its notable expression in other developmental cell types, including [neural crest cells](/details-cell/CL0011012) and [mesodermal cells](/details-cell/CL0000222). A second major site of [NAB2](/details-gene/4665) activity is within the respiratory system, where it is a highly significant gene in [epithelial cells of the lower respiratory tract](/details-cell/CL0002632) (CSI: 4.58) and [epithelial cells of the lung](/details-cell/CL0000082) (CSI: 4.40). This, along with its expression in [fibroblasts of the lung](/details-cell/CL0002553), suggests a role in maintaining the structural and functional integrity of lung tissue. Finally, [NAB2](/details-gene/4665) is prominently expressed in the nervous system. It is a significant marker in [interneurons](/details-cell/CL0000099), including specific subtypes like [pvalb GABAergic cortical interneurons](/details-cell/CL4023018) and [sst GABAergic cortical interneurons](/details-cell/CL4023017), as well as in glial cells like [astrocytes of the cerebral cortex](/details-cell/CL0002605). This broad neural expression pattern is consistent with its established role in nervous system development and function. ## Pathways and Molecular Function The molecular function of [NAB2](/details-gene/4665) is centered on its role as a transcriptional corepressor. It exerts its function through [protein binding](/details-link/GO:0005515), acting as a coregulator that modulates the activity of transcription factors. Studies have shown it acts as a corepressor for NGFI-A (Egr-1) and Krox20, which are induced by various proliferative and differentiative stimuli ([Link](https://doi.org/10.1128/mcb.16.7.3545)). Its localization to the [nucleoplasm](/details-link/GO:0005654) is consistent with this nuclear function. This regulatory role is reflected in its involvement in high-level biological processes such as [Developmental biology](/details-link/R-HSA-1266738) and [Regulation of dna-templated transcription](/details-link/GO:0006355). More specifically, [NAB2](/details-gene/4665) is a key component of pathways governing [Nervous system development](/details-link/R-HSA-9675108), including [NGF-stimulated transcription](/details-link/R-HSA-9031628) and [Signaling by receptor tyrosine kinases](/details-link/R-HSA-9006934). Its connection to the nervous system is particularly well-defined through its role in the [Egr2 and sox10-mediated initiation of schwann cell myelination](/details-link/R-HSA-9619665) pathway, which aligns with its functional annotation in [Schwann cell differentiation](/details-link/GO:0014037) and [Myelination](/details-link/GO:0042552). ## Research Directions The broad yet significant expression of [NAB2](/details-gene/4665) in progenitor, lung, and neural cells, combined with its function as a transcriptional repressor, opens several avenues for future research. **Proposed Hypotheses:** 1. Given its high significance in [progenitor cells](/details-cell/CL0011026) and its corepressor function, [NAB2](/details-gene/4665) may act as a crucial gatekeeper during cell differentiation by actively repressing gene programs associated with alternative cell fates, thereby ensuring lineage fidelity. 2. In the context of its high expression in [epithelial cells of the lung](/details-cell/CL0000082), [NAB2](/details-gene/4665) could be a homeostatic factor that suppresses pro-inflammatory or fibrotic pathways. Dysregulation or reduced expression of [NAB2](/details-gene/4665) might therefore be a contributing factor to the pathogenesis of diseases like pulmonary fibrosis. 3. Based on reports of its overexpression in melanoma ([Link](https://pubmed.ncbi.nlm.nih.gov/8649813/)), [NAB2](/details-gene/4665) may contribute to oncogenesis by repressing key tumor suppressor genes that are downstream targets of its transcription factor partners, effectively disabling cellular checkpoints. **Experimental Approach:** To test the hypothesis that [NAB2](/details-gene/4665) functions as a homeostatic suppressor of fibrosis in the lung (Hypothesis 2), a robust experimental model could be employed. One could utilize human induced pluripotent stem cell (iPSC)-derived lung organoids. In this system, [NAB2](/details-gene/4665) would be knocked out using CRISPR-Cas9. Control and NAB2-deficient organoids would then be challenged with a pro-fibrotic stimulus, such as TGF-beta. The resulting cellular and molecular changes could be analyzed via single-cell RNA sequencing to identify dysregulated gene networks (e.g., collagen synthesis, epithelial-mesenchymal transition) and by immunofluorescence staining to visualize changes in extracellular matrix deposition and cell morphology. **Therapeutic Potential:** As an intracellular nuclear protein, [NAB2](/details-gene/4665) is not a conventional drug target for antibodies. However, its role as a transcriptional corepressor makes it a potential target for therapeutic intervention, particularly in contexts where it is overexpressed, such as melanoma. The therapeutic strategy would likely involve **inhibition**. Developing small molecules that disrupt the protein-protein interaction between [NAB2](/details-gene/4665) and its specific oncogenic transcription factor partners (e.g., EGR1) could offer a targeted approach. However, given its widespread expression in essential cell types like progenitors and neurons, systemic inhibition poses a high risk of toxicity. Therefore, development of highly specific interaction inhibitors or targeted drug delivery systems would be necessary for any clinical application.

Genular Protein ID: 371943707

Symbol: NAB2_HUMAN

Name: NGFI-A-binding protein 2

UniProtKB Accession Codes:

Q15742 B2RAK3 O76006 Q14797

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 2 GO 11 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 Pumba 1 RNAct 1 Reactome 2 RefSeq 2 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8668170

Title: NAB2, a corepressor of NGFI-A (Egr-1) and Krox20, is induced by proliferative and differentiative stimuli.

PubMed ID: 8668170

DOI: 10.1128/mcb.16.7.3545

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 8649813

Title: Mader: a novel nuclear protein over expressed in human melanomas.

PubMed ID: 8649813

PubMed ID: 9126479

Title: The Nab2 and Stat6 genes share a common transcription termination region.

PubMed ID: 9126479

DOI: 10.1006/geno.1997.4609

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 21836637

Title: The transcription factor Krox20 is an E3 ligase that sumoylates its Nab coregulators.

PubMed ID: 21836637

DOI: 10.1038/embor.2011.152

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

Sequence Information:

  • Length: 525
  • Mass: 56594
  • Checksum: 38CF6CFEFE3756F9
  • Sequence:
    • MHRAPSPTAE QPPGGGDSAR RTLQPRLKPS ARAMALPRTL GELQLYRVLQ RANLLSYYET 
FIQQGGDDVQ QLCEAGEEEF LEIMALVGMA TKPLHVRRLQ KALREWATNP GLFSQPVPAV 
PVSSIPLFKI SETAGTRKGS MSNGHGSPGE KAGSARSFSP KSPLELGEKL SPLPGGPGAG 
DPRIWPGRST PESDVGAGGE EEAGSPPFSP PAGGGVPEGT GAGGLAAGGT GGGPDRLEPE 
MVRMVVESVE RIFRSFPRGD AGEVTSLLKL NKKLARSVGH IFEMDDNDSQ KEEEIRKYSI 
IYGRFDSKRR EGKQLSLHEL TINEAAAQFC MRDNTLLLRR VELFSLSRQV ARESTYLSSL 
KGSRLHPEEL GGPPLKKLKQ EVGEQSHPEI QQPPPGPESY VPPYRPSLEE DSASLSGESL 
DGHLQAVGSC PRLTPPPADL PLALPAHGLW SRHILQQTLM DEGLRLARLV SHDRVGRLSP 
CVPAKPPLAE FEEGLLDRCP APGPHPALVE GRRSSVKVEA EASRQ