Details for: ENTR1

Gene ID: 10807

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: ENTR1

Ensembl ID: ENSG00000165689

Description: endosome associated trafficking regulator 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • intermediate monocyte CL0002393
    CSI 3.14
    rCSI 4.73%
    PRS 98.7
  • stem cell CL0000034
    CSI 2.82
    rCSI 2.72%
    PRS 95.65
  • group 3 innate lymphoid cell CL0001071
    CSI 2.81
    rCSI 2.11%
    PRS 98.01
  • respiratory suprabasal cell CL4033048
    CSI 2.76
    rCSI 3.54%
    PRS 97.57
  • extravillous trophoblast CL0008036
    CSI 2.68
    rCSI 3.31%
    PRS 95.87
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.46
    rCSI 3.07%
    PRS 89.76
  • hepatocyte CL0000182
    CSI 2.36
    rCSI 4.22%
    PRS 95.41
  • centrilobular region hepatocyte CL0019029
    CSI 2.04
    rCSI 5.33%
    PRS 93.73
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.02
    rCSI 2.41%
    PRS 91.25
  • club cell CL0000158
    CSI 1.77
    rCSI 2.59%
    PRS 95.41
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.76
    rCSI 3.95%
    PRS 91.51
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.75
    rCSI 3.09%
    PRS 91.02
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.59
    rCSI 2.67%
    PRS 91.39
  • neural progenitor cell CL0011020
    CSI 0.99
    rCSI 4.37%
    PRS 89.85
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.94
    rCSI 3.54%
    PRS 91.14
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.94
    rCSI 2.27%
    PRS 89.7
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.82
    rCSI 2.95%
    PRS 89.96
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.8
    rCSI 2.49%
    PRS 91.84
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.52
    rCSI 3.09%
    PRS 91.35

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):
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    • 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 [ENTR1](/details-gene/10807) (endosome associated trafficking regulator 1) is a protein-coding gene located on chromosome 9q34.3. Functionally, it is a versatile regulator involved in fundamental cellular processes, including endocytic recycling, cell division, and the assembly of cilia. Consistent with these core functions, [ENTR1](/details-gene/10807) shows significant expression across a diverse range of cell types. **Overall**, it is a key marker in immune cells such as the [intermediate monocyte](/details-cell/CL0002393), various progenitor populations including the [stem cell](/details-cell/CL0000034), and specialized cell types like the [respiratory suprabasal cell](/details-cell/CL4033048) and [extravillous trophoblast](/details-cell/CL0008036), highlighting its importance in both renewing tissues and terminally differentiated cells with high trafficking or structural demands. ## Cellular Roles and Expression Landscape The expression profile of [ENTR1](/details-gene/10807) suggests a role in multiple, distinct biological systems, reflective of its involvement in ubiquitous cellular machinery. **Overall**, the gene's significance is highest in the [intermediate monocyte](/details-cell/CL0002393) (CSI: 3.14), suggesting a critical role in the endocytic and trafficking pathways that govern monocyte surveillance and differentiation. Its high expression extends to other immune populations, including the [group 3 innate lymphoid cell](/details-cell/CL0001071) (CSI: 2.81), indicating a potential function in mucosal immunity and tissue homeostasis. The gene is also prominently expressed in progenitor and actively dividing cells, as shown by its high significance in the [stem cell](/details-cell/CL0000034) (CSI: 2.82) and [neural progenitor cell](/details-cell/CL0011020) (CSI: 0.99). This pattern is consistent with its established role in cytokinesis. Furthermore, [ENTR1](/details-gene/10807) is significant in a variety of specialized epithelial and secretory cells, including the [respiratory suprabasal cell](/details-cell/CL4033048) (CSI: 2.76), [extravillous trophoblast](/details-cell/CL0008036) (CSI: 2.68), [hepatocyte](/details-cell/CL0000182) (CSI: 2.36), and [club cell](/details-cell/CL0000158) (CSI: 1.77). This expression likely reflects its function in protein transport and ciliogenesis, processes vital for barrier function, secretion, and detoxification. Finally, its relevance in distinct neuronal subtypes, such as the [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 2.46) and [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 2.02), points towards a specialized role in neuronal development or signaling. ## Pathways and Molecular Function Functional annotation data reveals that [ENTR1](/details-gene/10807) participates in three major cellular activities: vesicular trafficking, cell cycle progression, and ciliogenesis. **Vesicular Trafficking:** [ENTR1](/details-gene/10807) is a key component of the endocytic system. It localizes to the [endosome](/details-cell/GO:0005768), including the [early endosome](/details-cell/GO:0005769) and [recycling endosome](/details-cell/GO:0055037), and is part of the [retromer complex](/details-cell/GO:0030904). Its function in [endocytic recycling](/details-cell/GO:0032456) and general [protein transport](/details-cell/GO:0015031) is critical for sorting cargo proteins back to the plasma membrane ([Link](https://doi.org/10.1242/jcs.156299)). This function is particularly relevant for its high expression in monocytes and hepatocytes, cells that rely heavily on endocytosis for immune surveillance and metabolic processing. **Cell Division:** The gene plays a direct role in [cell division](/details-cell/GO:0051301), specifically in the [regulation of cytokinesis](/details-cell/GO:0032465). During the final stages of mitosis, it localizes to the [midbody](/details-cell/GO:0030496) and interacts with other proteins to ensure the proper separation of daughter cells ([Link](https://doi.org/10.1038/onc.2012.485)). This function aligns with its high significance in progenitor and stem cell populations. **Ciliogenesis:** [ENTR1](/details-gene/10807) is a [positive regulator of cilium assembly](/details-cell/GO:0045724) and protein localization to the cilium ([Link](https://doi.org/10.1038/srep35399)). Its presence at the [ciliary basal body](/details-cell/GO:0036064), the organizing center for cilia, underscores its importance in forming this essential signaling organelle. This role is consistent with its expression in cells known to possess cilia, such as respiratory [club cell](/details-cell/CL0000158)s and certain neuronal subtypes. ## Research Directions The multifaceted roles of [ENTR1](/details-gene/10807) in fundamental cellular processes present several avenues for future research, particularly in immunology, neuroscience, and oncology. **Proposed Testable Hypotheses:** 1. Given its high significance in the [intermediate monocyte](/details-cell/CL0002393) and its function in endocytic recycling, we hypothesize that [ENTR1](/details-gene/10807) is essential for the turnover and surface expression of chemokine receptors (e.g., CCR2, CX3CR1), thereby controlling monocyte migration and inflammatory response. 2. Based on its expression in distinct neuronal subtypes and its established role in ciliogenesis, we hypothesize that [ENTR1](/details-gene/10807) is required for the formation and function of primary cilia on cortical interneurons, which in turn modulates their response to key developmental and homeostatic signals like Sonic hedgehog (Shh). 3. Since [ENTR1](/details-gene/10807) was first identified as a serologically defined colon cancer antigen ([Link](https://doi.org/10.1002/(sici)1097-0215(19980529)76:5<652::aid-ijc7>3.0.co;2-p)) and regulates cytokinesis, we hypothesize that its overexpression or mutation in cancer cells leads to cytokinesis failure, resulting in aneuploidy and contributing to genomic instability and tumor progression. **Proposed Key Experiment:** To test the first hypothesis regarding the role of [ENTR1](/details-gene/10807) in monocyte function, one could perform a CRISPR-Cas9-mediated knockout of [ENTR1](/details-gene/10807) in the human monocytic cell line THP-1 or in primary human CD14+ monocytes. The functional consequences would be assessed by measuring changes in surface receptor levels (e.g., CCR2) via flow cytometry following chemokine stimulation, and by evaluating the cells' migratory capacity in response to a chemoattractant gradient using a transwell migration assay. **Therapeutic Potential:** The involvement of [ENTR1](/details-gene/10807) in cell division makes it a potential target for cancer therapy. As its dysregulation could promote genomic instability, its **inhibition** may selectively harm rapidly proliferating cancer cells that are already prone to mitotic errors. However, its widespread expression in healthy tissues, including immune and progenitor cells, poses a significant risk for on-target toxicity. Therefore, a successful therapeutic strategy would likely require targeted delivery systems, such as antibody-drug conjugates or nanoparticle-encapsulated siRNAs, to specifically direct inhibitors to tumor cells while sparing healthy tissues.

Genular Protein ID: 2133124606

Symbol: ENTR1_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q96C92 A6NCP1 O60525 Q5SXN1 Q5SXN2 Q5SXN3 Q5SXN4 Q5SXN8 Q6V704 Q9NVY5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 3 ExpressionAtlas 1 GO 13 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 Pumba 1 RNAct 1 RefSeq 3 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: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 9610721

Title: Characterization of human colon cancer antigens recognized by autologous antibodies.

PubMed ID: 9610721

DOI: 10.1002/(sici)1097-0215(19980529)76:5&lt;652::aid-ijc7&gt;3.0.co;2-p

PubMed ID: 17081983

Title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

PubMed ID: 17081983

DOI: 10.1016/j.cell.2006.09.026

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 23186163

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

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 23108400

Title: The serologically defined colon cancer antigen-3 interacts with the protein tyrosine phosphatase PTPN13 and is involved in the regulation of cytokinesis.

PubMed ID: 23108400

DOI: 10.1038/onc.2012.485

PubMed ID: 25278552

Title: Identification of molecular heterogeneity in SNX27-retromer-mediated endosome-to-plasma-membrane recycling.

PubMed ID: 25278552

DOI: 10.1242/jcs.156299

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: 27812135

Title: Characterization and Genetic Analyses of New Genes Coding for NOD2 Interacting Proteins.

PubMed ID: 27812135

DOI: 10.1371/journal.pone.0165420

PubMed ID: 27767179

Title: The serologically defined colon cancer antigen-3 (SDCCAG3) is involved in the regulation of ciliogenesis.

PubMed ID: 27767179

DOI: 10.1038/srep35399

Sequence Information:

  • Length: 435
  • Mass: 47961
  • Checksum: 03EBD9512232B5E3
  • Sequence:
    • MSGYQRRPGA TPLSRARSLA IPDAPAFYER RSCLPQLNCE RPHGRDLDSP FFGIRPAFMC 
YVPSPVLASV GDTDFGYGKG KCSKQSPSGA HGTHFGDDRF EDLEEANPFS FREFLKTKNL 
GLSKEDPASR IYAKEASRHS LGLDHNSPPS QTGGYGLEYQ QPFFEDPTGA GDLLDEEEDE 
DTGWSGAYLP SAIEQTHPER VPAGTSPCST YLSFFSTPSE LAGPESLPSW ALSDTDSRVS 
PASPAGSPSA DFAVHGESLG DRHLRTLQIS YDALKDENSK LRRKLNEVQS FSEAQTEMVR 
TLERKLEAKM IKEESDYHDL ESVVQQVEQN LELMTKRAVK AENHVVKLKQ EISLLQAQVS 
NFQRENEALR CGQGASLTVV KQNADVALQN LRVVMNSAQA SIKQLVSGAE TLNLVAEILK 
SIDRISEVKD EEEDS