Details for: REM2

Gene ID: 161253

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: REM2

Ensembl ID: ENSG00000139890

Description: RRAD and GEM like GTPase 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • neural progenitor cell CL0011020
    CSI 2.8
    rCSI 12.3%
    PRS 99.43

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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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 [REM2](/details-gene/161253) is a protein-coding gene that produces a small GTP-binding protein belonging to the RRAD and GEM like GTPase family. Functionally, [REM2](/details-gene/161253) is annotated as a GTPase and a regulator of calcium channel activity, localizing primarily to the plasma membrane. Expression data indicates a significant role for this gene within [neural progenitor cell](/details-cell/CL0011020)s, suggesting its involvement in the molecular processes governing neural development. Its initial characterization was part of comprehensive human cDNA sequencing projects [Link](https://doi.org/10.1038/ng1285), [Link](https://doi.org/10.1101/gr.2596504). ## Cellular Roles and Expression Landscape The expression profile of [REM2](/details-gene/161253) highlights its specialized function within the nervous system. **Overall**, the gene shows its most significant expression in [neural progenitor cell](/details-cell/CL0011020)s (CSI: 2.80). This specific expression pattern suggests that [REM2](/details-gene/161253) is not a broadly expressed housekeeping gene but rather plays a key role in the biology of this cell type. Its activity in [neural progenitor cell](/details-cell/CL0011020)s points toward a potential function in regulating cell fate decisions, proliferation, or the initial stages of neuronal differentiation. The lack of significant expression in other cell types within the provided data implies a highly specific role related to neurogenesis. ## Pathways and Molecular Function The known molecular functions of [REM2](/details-gene/161253) are consistent with its role as a signaling protein. It possesses GTP binding ([GO:0005525](https://www.ebi.ac.uk/QuickGO/term/GO:0005525)) and GTPase activity ([GO:0003924](https://www.ebi.ac.uk/QuickGO/term/GO:0003924)), which are characteristic of molecular switches that cycle between active (GTP-bound) and inactive (GDP-bound) states. A primary annotated function for [REM2](/details-gene/161253) is its involvement in calcium channel regulator activity ([GO:0005246](https://www.ebi.ac.uk/QuickGO/term/GO:0005246)). This function is carried out at the [plasma membrane](/details-cell/GO:0005886) ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO:0005886)), where the protein is predominantly located. The regulation of calcium influx is a critical process in neuronal development, influencing events such as gene expression, proliferation, and differentiation. The specific expression of [REM2](/details-gene/161253) in [neural progenitor cell](/details-cell/CL0011020)s, combined with its function as a calcium channel modulator, strongly suggests it is a key component of the signaling network that controls the transition from a progenitor state to a mature neuron. ## Research Directions The specific expression of [REM2](/details-gene/161253) in [neural progenitor cell](/details-cell/CL0011020)s and its function as a calcium channel regulator offer several avenues for future investigation. **Testable Hypotheses:** 1. **[REM2](/details-gene/161253) acts as a brake on neuronal differentiation:** It may function to inhibit voltage-gated calcium channels in [neural progenitor cell](/details-cell/CL0011020)s, thereby maintaining their proliferative and undifferentiated state. Downregulation of [REM2](/details-gene/161253) would then be a prerequisite for initiating differentiation into mature neurons. 2. **[REM2](/details-gene/161253) modulates neurite outgrowth:** The GTPase activity of [REM2](/details-gene/161253) could be crucial for cytoskeletal dynamics downstream of calcium signaling, specifically regulating the initiation and extension of axons and dendrites during early neuronal morphogenesis. **Proposed Experimental Approach:** To test the hypothesis that [REM2](/details-gene/161253) inhibits neuronal differentiation (Hypothesis 1), a loss-of-function study could be performed using a human induced pluripotent stem cell (iPSC)-derived [neural progenitor cell](/details-cell/CL0011020) model. - **Method:** Utilize CRISPR-Cas9 to generate a stable [REM2](/details-gene/161253) knockout or CRISPR interference (CRISPRi) to achieve inducible knockdown in the progenitor cell line. - **Assays:** Compare the differentiation trajectory of knockout/knockdown cells to isogenic controls. Assess the rate of differentiation and neuronal maturation by quantifying the expression of progenitor (e.g., SOX2, PAX6) and neuronal (e.g., Tuj1, MAP2) markers over time via immunocytochemistry and quantitative PCR. - **Functional Validation:** Perform patch-clamp electrophysiology on both control and [REM2](/details-gene/161253)-deficient cells to directly measure changes in voltage-gated calcium channel current density and kinetics, confirming the gene's role as a channel regulator in this specific cellular context. **Therapeutic Potential:** Given its specific role in [neural progenitor cell](/details-cell/CL0011020) biology, [REM2](/details-gene/161253) presents a potential target for regenerative medicine and neurodevelopmental disorders. As a GTPase, it is a potentially druggable protein class. If it indeed functions to maintain the progenitor state, targeted **inhibition** of [REM2](/details-gene/161253) could be explored as a strategy to enhance or direct the differentiation of stem cells into specific neuronal subtypes for cell-based therapies for neurodegenerative diseases. Further research is required to validate its role and assess the feasibility of modulating its activity without adverse effects on normal neurogenesis.

Genular Protein ID: 2412441743

Symbol: REM2_HUMAN

Name: GTP-binding protein REM 2

UniProtKB Accession Codes:

Q8IYK8 B7Z5P1 Q8N8R8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 3 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 2 EvolutionaryTrace 1 GO 4 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 1 SMART 3 SMR 1 STRING 1 SUPFAM 1 SignaLink 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: 12508121

Title: The DNA sequence and analysis of human chromosome 14.

PubMed ID: 12508121

DOI: 10.1038/nature01348

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: 340
  • Mass: 37139
  • Checksum: 7043E32471EA18DA
  • Sequence:
    • MHTDLDTDMD MDTETTALCP SGSRRASPPG TPTPEADATL LKKSEKLLAE LDRSGLPSAP 
GAPRRRGSMP VPYKHQLRRA QAVDELDWPP QASSSGSSDS LGSGEAAPAQ KDGIFKVMLV 
GESGVGKSTL AGTFGGLQGD SAHEPENPED TYERRIMVDK EEVTLVVYDI WEQGDAGGWL 
RDHCLQTGDA FLIVFSVTDR RSFSKVPETL LRLRAGRPHH DLPVILVGNK SDLARSREVS 
LEEGRHLAGT LSCKHIETSA ALHHNTRELF EGAVRQIRLR RGRNHAGGQR PDPGSPEGPA 
PPARRESLTK KAKRFLANLV PRNAKFFKQR SRSCHDLSVL