Details for: MAGEE2

Gene ID: 139599

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: MAGEE2

Ensembl ID: ENSG00000186675

Description: MAGE family member E2

Cell Significance Landscape

Associated with

Significant Cells

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

  • glutamatergic neuron CL0000679
    CSI 40.69
    rCSI 83.61%
    PRS 1.15
  • neural progenitor cell CL0011020
    CSI -31.52
    rCSI -100%
    PRS 1.02

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

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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    • 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 [MAGEE2](/details-gene/139599) is a protein-coding gene located on the X chromosome, belonging to the Melanoma-Associated Antigen (MAGE) family of proteins. Functionally, it is annotated as a nuclear protein involved in the negative regulation of transcription and protein binding. Expression data indicates that **Overall**, [MAGEE2](/details-gene/139599) is a highly significant marker for [glutamatergic neuron](/details-cell/CL0000679)s, suggesting a specialized role in the function or maintenance of this mature neuronal cell type. Its clinical relevance is noted through its association with OMIM entry [300760](https://omim.org/entry/300760). The characterization of this gene is supported by large-scale cDNA and genome sequencing projects ([Link](https://doi.org/10.1038/ng1285), [Link](https://doi.org/10.1038/nature03440)). ## Cellular Roles and Expression Landscape The expression profile of [MAGEE2](/details-gene/139599) points to a highly specific role within the nervous system. **Overall**, the gene's most significant expression is observed in [glutamatergic neuron](/details-cell/CL0000679) (CSI: 40.69), identifying it as a key molecular feature of this excitatory neuron population. This specificity is further sharpened by its notable lack of expression in related precursor cells. The gene shows significant negative association with [neural progenitor cell](/details-cell/CL0011020) (CSI: -31.52). This strong contrast suggests that [MAGEE2](/details-gene/139599) is likely not involved in neurogenesis or the maintenance of a progenitor state, but rather is upregulated during or after terminal differentiation. Its expression pattern is consistent with a function dedicated to establishing or maintaining the specialized identity of mature [glutamatergic neuron](/details-cell/CL0000679)s. ## Pathways and Molecular Function The known molecular functions of [MAGEE2](/details-gene/139599) align well with its observed cellular expression pattern. The gene product is localized to the [nucleus](/details-cell/GO:0005634) and participates in the negative regulation of transcription by RNA polymerase II ([GO:0000122](https://www.ebi.ac.uk/QuickGO/term/GO:0000122)). This role as a transcriptional repressor is likely central to its function in [glutamatergic neuron](/details-cell/CL0000679)s. By suppressing the expression of specific target genes, [MAGEE2](/details-gene/139599) may help maintain the precise transcriptional program required for glutamatergic identity and function, potentially by silencing genes associated with pluripotency, proliferation, or alternative neuronal fates. Its annotation for [protein binding](/details-cell/GO:0005515) suggests it likely functions as part of a larger protein complex to exert its regulatory effects. ## Research Directions The specific expression of [MAGEE2](/details-gene/139599) in mature [glutamatergic neuron](/details-cell/CL0000679)s, coupled with its role as a transcriptional repressor, provides a foundation for several testable hypotheses. 1. **Hypothesis on Neuronal Identity:** [MAGEE2](/details-gene/139599) is a critical factor for maintaining the terminally differentiated state of [glutamatergic neuron](/details-cell/CL0000679)s by actively repressing a suite of genes characteristic of [neural progenitor cell](/details-cell/CL0011020)s. Its downregulation could lead to cellular de-differentiation or instability. 2. **Hypothesis on Neurological Disease:** Loss-of-function mutations or epigenetic silencing of [MAGEE2](/details-gene/139599) may contribute to neurological disorders involving glutamatergic excitotoxicity or dysfunction, as the failure to repress target genes could disrupt cellular homeostasis. **Experimental Approach:** To test the hypothesis that [MAGEE2](/details-gene/139599) is essential for maintaining the glutamatergic phenotype, one could employ a CRISPR interference (CRISPRi) system to specifically knock down its expression in a human iPSC-derived glutamatergic neuron culture. The impact of the knockdown would be assessed through a combination of single-cell RNA sequencing to identify derepressed progenitor-associated genes, and functional assays, such as patch-clamp electrophysiology, to measure changes in synaptic activity and neuronal firing properties. **Therapeutic Potential:** As an intracellular nuclear protein functioning as a transcriptional regulator, [MAGEE2](/details-gene/139599) is a challenging therapeutic target for traditional small molecule inhibitors or antibodies. If its loss-of-function is implicated in disease, a therapeutic strategy would likely need to focus on restoring its activity. This could potentially involve gene therapy approaches to reintroduce the functional gene or the development of novel small molecules that stabilize the MAGEE2 protein or enhance its assembly into its repressive complex. Therefore, activation or stabilization, rather than inhibition, would be the probable therapeutic goal.

Genular Protein ID: 2901374499

Symbol: MAGE2_HUMAN

Name: Melanoma-associated antigen E2

UniProtKB Accession Codes:

Q8TD90 Q5JSI5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 GO 2 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 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: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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

Sequence Information:

  • Length: 523
  • Mass: 60378
  • Checksum: FB668B47A2B72AFB
  • Sequence:
    • MSLVSQNARH CSAEITADYG DGRGEIQATN ASGSPTSMLV VDAPQCPQAP INSQCVNTSQ 
AVQDPNDLEV LIDEQSRRLG ALRVHDPLED RSIALVNFMR MKSQTEGSIQ QSEMLEFLRE 
YSDQFPEILR RASAHLDQVF GLNLRVIDPQ ADTYNLVSKR GFQITDRIAE SLDMPKASLL 
ALVLGHILLN GNRAREASIW DLLLKVDMWD KPQRINNLFG NTRNLLTTDF VCMRFLEYWP 
VYGTNPLEFE FLWGSRAHRE ITKMEALKFV SDAHDEEPWS WPEEYNKALE GDKTKERSLT 
AGLEFWSEDT MNDKANDLVQ LAISVTEEML PIHQDELLAH TGKEFEDVFP NILNRATLIL 
DMFYGLSLIE VDTSEHIYLL VQQPESEEEQ VMLESLGRPT QEYVMPILGL IFLMGNRVKE 
ANVWNLLRRF SVDVGRKHSI TRKLMRQRYL ECRPLSYSNP VEYELLWGPR AHHETIKMKV 
LEYMARLYRK RPQNWPEQYR EAVEDEEARA KSEATIMFFL DPT