Details for: NLE1

Gene ID: 54475

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: NLE1

Ensembl ID: ENSG00000073536

Description: notchless homolog 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 4.79
    rCSI 5.8%
    PRS 91.55
  • neural crest cell CL0011012
    CSI 4.45
    rCSI 3.52%
    PRS 98.79
  • stem cell CL0000034
    CSI 3.5
    rCSI 3.38%
    PRS 99.1
  • hematopoietic stem cell CL0000037
    CSI 3.39
    rCSI 2.25%
    PRS 99.49
  • common myeloid progenitor CL0000049
    CSI 3.34
    rCSI 2.7%
    PRS 99.69
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 3.29
    rCSI 2.97%
    PRS 99.21
  • epithelial cell CL0000066
    CSI 3.22
    rCSI 4.94%
    PRS 95.97
  • basal cell of epidermis CL0002187
    CSI 1.75
    rCSI 3.11%
    PRS 88.53
  • melanocyte of skin CL1000458
    CSI 1.49
    rCSI 2.04%
    PRS 89.84
  • helper T cell CL0000912
    CSI 1.48
    rCSI 2.1%
    PRS 96.86
  • cytotoxic T cell CL0000910
    CSI 1.48
    rCSI 8.49%
    PRS 97.22

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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  • 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 [NLE1](/details-gene/54475) (Notchless homolog 1) is a protein-coding gene located on chromosome 17q12. It functions as a crucial regulator in fundamental developmental and cellular processes. Its protein product localizes to the nucleus and is primarily involved in modulating the Notch and Wnt signaling pathways, which are critical for cell fate decisions. Functionally, [NLE1](/details-gene/54475) is annotated with roles in the [mitotic cell cycle](/details-ontology/GO:0000278), [hematopoietic stem cell homeostasis](/details-ontology/GO:0061484), and the morphogenesis of multiple systems. **Overall**, its expression profile reflects these functions, showing high significance in various stem and progenitor cells, including [hematopoietic stem cell](/details-cell/CL0000037)s and [neural crest cell](/details-cell/CL0011012), as well as in specific differentiated cell types like [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203), suggesting a broad role in both development and the maintenance of cellular identity. ## Cellular Roles and Expression Landscape The expression pattern of [NLE1](/details-gene/54475) highlights its importance in undifferentiated and highly proliferative cell populations. **Overall**, the gene shows its highest significance in cells associated with lineage commitment and memory, including [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 4.79) and [neural crest cell](/details-cell/CL0011012) (CSI: 4.45). This is strongly supported by its high CSI values across the hematopoietic progenitor hierarchy, including [stem cell](/details-cell/CL0000034) (CSI: 3.50), [hematopoietic stem cell](/details-cell/CL0000037) (CSI: 3.39), [common myeloid progenitor](/details-cell/CL0000049) (CSI: 3.34), and [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 3.29). This profile suggests a critical function for [NLE1](/details-gene/54475) in maintaining the pluripotency and self-renewal capacity of stem cells, likely through its documented role in regulating key developmental signaling pathways. Furthermore, its notable expression in mature lymphocyte populations such as [helper T cell](/details-cell/CL0000912) and [cytotoxic T cell](/details-cell/CL0000910) (CSI: 1.48 for both), particularly memory subsets, points towards an additional role in the long-term maintenance and function of the adaptive immune system. The gene's significance in [epithelial cell](/details-cell/CL0000066)s and [basal cell of epidermis](/details-cell/CL0002187) is consistent with its involvement in morphogenesis and tissue homeostasis. ## Pathways and Molecular Function The functions of [NLE1](/details-gene/54475) are deeply rooted in the regulation of core cellular signaling and developmental programs. Its primary annotated molecular function is [protein binding](/details-ontology/GO:0005515), and it is localized within the [nucleoplasm](/details-ontology/GO:0005654) and [nucleolus](/details-ontology/GO:0005730), as confirmed by proteomic studies ([Link](https://doi.org/10.1091/mbc.e02-05-0271)). This nuclear localization is consistent with its role in modulating transcription-dependent signaling pathways. Key biological processes associated with [NLE1](/details-gene/54475) include: * **Signaling Pathway Regulation:** It is a known regulator of the [Notch signaling pathway](/details-ontology/GO:0008593) and is also involved in the [positive regulation of canonical wnt signaling pathway](/details-ontology/GO:0090263). These pathways are essential for embryonic development and stem cell maintenance. * **Cell Cycle Control:** The gene participates in the [mitotic cell cycle](/details-ontology/GO:0000278) and its [negative regulation](/details-ontology/GO:0045930), which aligns with its high expression in rapidly dividing progenitor cells. * **Development and Homeostasis:** It plays a role in [hematopoietic stem cell homeostasis](/details-ontology/GO:0061484) and the development of various tissues, including the kidneys ([GO:0001822](/details-ontology/GO:0001822)) and skeletal system ([GO:0048705](/details-ontology/GO:0048705)). This functional profile provides a molecular basis for its observed expression landscape in stem and developmental cell types. ## Research Directions The established roles of [NLE1](/details-gene/54475) in regulating the Notch and Wnt pathways, as well as the cell cycle, suggest that its dysregulation could be a driver in developmental disorders and malignancies. Its high significance in both hematopoietic stem cells and memory T cells presents intriguing avenues for further investigation. **Proposed Hypotheses:** 1. Given its critical role in [hematopoietic stem cell homeostasis](/details-ontology/GO:0061484) and high expression in progenitor cells, it is hypothesized that **loss-of-function of [NLE1](/details-gene/54475) in hematopoietic stem cells impairs their self-renewal and leads to lineage bias during differentiation due to aberrant Wnt and Notch signaling.** 2. Based on its top CSI score in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203), it is hypothesized that **[NLE1](/details-gene/54475) is essential for the establishment and long-term persistence of T-cell memory, possibly by regulating the balance between quiescence and proliferative potential.** **Suggested Experimental Approach:** To test the first hypothesis, a combination of *in vitro* and *in vivo* studies could be employed. Primary human CD34+ hematopoietic stem and progenitor cells could be isolated and subjected to CRISPR-Cas9-mediated knockout or shRNA-mediated knockdown of [NLE1](/details-gene/54475). The functional consequences would be assessed by comparing modified cells to controls in colony-forming unit (CFU) assays to measure differentiation potential into various lineages (e.g., erythroid, myeloid). To assess self-renewal, these cells could be serially transplanted into immunodeficient mice, with engraftment and lineage output monitored over time. RNA-sequencing of the modified stem cells would be used to confirm the dysregulation of downstream targets in the Notch and Wnt signaling pathways. **Therapeutic Potential:** As a nuclear protein involved in fundamental processes like cell cycle control and developmental signaling, [NLE1](/details-gene/54475) presents a challenging but potentially valuable therapeutic target, particularly in oncology. Its role suggests that its aberrant overexpression could promote uncontrolled proliferation. Therefore, therapeutic strategies would likely focus on **inhibition**. However, its nuclear localization makes it inaccessible to antibody-based therapies, suggesting a need for small molecule inhibitors or novel modalities like targeted protein degradation (PROTACs). A significant hurdle would be potential on-target toxicity in healthy stem and progenitor cell populations, necessitating a therapeutic window where cancer cells are more dependent on [NLE1](/details-gene/54475) function than their normal counterparts.

Genular Protein ID: 1872793173

Symbol: NLE1_HUMAN

Name: Notchless protein homolog 1

UniProtKB Accession Codes:

Q9NVX2 O60868 Q59GJ8 Q9BU54

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 EMDB 10 Ensembl 2 ExpressionAtlas 1 GO 12 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 11 PDBsum 11 PRINTS 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 3 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

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: 11124703

Title: Characterization of 16 novel human genes showing high similarity to yeast sequences.

PubMed ID: 11124703

DOI: 10.1002/1097-0061(200101)18:1<69::aid-yea647>3.0.co;2-h

PubMed ID: 12429849

Title: Functional proteomic analysis of human nucleolus.

PubMed ID: 12429849

DOI: 10.1091/mbc.e02-05-0271

PubMed ID: 17525332

Title: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.

PubMed ID: 17525332

DOI: 10.1126/science.1140321

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: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22223895

Title: Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.

PubMed ID: 22223895

DOI: 10.1074/mcp.m111.015131

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

PubMed ID: 26601951

Title: The crystal structure of the ubiquitin-like domain of ribosome assembly factor Ytm1 and characterization of its interaction with the AAA-ATPase Midasin.

PubMed ID: 26601951

DOI: 10.1074/jbc.m115.693259

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 485
  • Mass: 53320
  • Checksum: E2E638B13884BC07
  • Sequence:
    • MAAAVPDEAV ARDVQRLLVQ FQDEGGQLLG SPFDVPVDIT PDRLQLVCNA LLAQEDPLPL 
AFFVHDAEIV SSLGKTLESQ AVETEKVLDI IYQPQAIFRV RAVTRCTSSL EGHSEAVISV 
AFSPTGKYLA SGSGDTTVRF WDLSTETPHF TCKGHRHWVL SISWSPDGRK LASGCKNGQI 
LLWDPSTGKQ VGRTLAGHSK WITGLSWEPL HANPECRYVA SSSKDGSVRI WDTTAGRCER 
ILTGHTQSVT CLRWGGDGLL YSASQDRTIK VWRAHDGVLC RTLQGHGHWV NTMALSTDYA 
LRTGAFEPAE ASVNPQDLQG SLQELKERAL SRYNLVRGQG PERLVSGSDD FTLFLWSPAE 
DKKPLTRMTG HQALINQVLF SPDSRIVASA SFDKSIKLWD GRTGKYLASL RGHVAAVYQI 
AWSADSRLLV SGSSDSTLKV WDVKAQKLAM DLPGHADEVY AVDWSPDGQR VASGGKDKCL 
RIWRR