Details for: PLAGL2

Gene ID: 5326

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: PLAGL2

Ensembl ID: ENSG00000126003

Description: PLAG1 like zinc finger 2

Cell Significance Landscape

Associated with

  • Chylomicron assembly
    (GO:0034378)
  • Dna-binding transcription activator activity, rna polymerase ii-specific
    (GO:0001228)
  • Dna-binding transcription factor activity
    (GO:0003700)
  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Lipid metabolic process
    (GO:0006629)
  • Metal ion binding
    (GO:0046872)
  • Nucleus
    (GO:0005634)
  • Positive regulation of intrinsic apoptotic signaling pathway
    (GO:2001244)
  • Positive regulation of transcription by rna polymerase ii
    (GO:0045944)
  • Post-embryonic development
    (GO:0009791)
  • Protein binding
    (GO:0005515)
  • Regulation of transcription by rna polymerase ii
    (GO:0006357)
  • Sequence-specific dna binding
    (GO:0043565)

Significant Cells

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

  • melanocyte of skin CL1000458
    CSI 9.66
    rCSI 13.17%
    PRS 70.78
  • glutamatergic neuron CL0000679
    CSI 5.85
    rCSI 12.02%
    PRS 86.14
  • GABAergic neuron CL0000617
    CSI 4.09
    rCSI 13.69%
    PRS 85.01
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 3.58
    rCSI 2.75%
    PRS 97.06
  • ciliated epithelial cell CL0000067
    CSI 3.54
    rCSI 3.11%
    PRS 88.43
  • common myeloid progenitor CL0000049
    CSI 2.8
    rCSI 2.26%
    PRS 95.63
  • stem cell CL0000034
    CSI 2.66
    rCSI 2.57%
    PRS 92.58
  • myeloid leukocyte CL0000766
    CSI 2.66
    rCSI 2.45%
    PRS 95.84
  • intestinal epithelial cell CL0002563
    CSI 2.56
    rCSI 2.68%
    PRS 93.12
  • renal beta-intercalated cell CL0002201
    CSI 2.54
    rCSI 6.04%
    PRS 95.08
  • colon epithelial cell CL0011108
    CSI 2.48
    rCSI 2.6%
    PRS 93.09
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.29
    rCSI 2.2%
    PRS 93.73
  • enterocyte CL0000584
    CSI 2.04
    rCSI 3.3%
    PRS 92.26
  • promonocyte CL0000559
    CSI 1.98
    rCSI 3.39%
    PRS 95.76
  • basal cell CL0000646
    CSI 1.94
    rCSI 2.6%
    PRS 92.68
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.5
    rCSI 4.03%
    PRS 95.89
  • retinal cone cell CL0000573
    CSI 1.31
    rCSI 2.12%
    PRS 89.06

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.

Comma-separated if multiple.
Comma-separated if multiple.
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)

Loading network (please wait)...

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 [PLAGL2](/details-gene/5326) (PLAG1 like zinc finger 2) is a protein-coding gene located on chromosome 20q11.21. It encodes a zinc finger transcription factor that plays a crucial role in regulating gene expression by binding to DNA. Functionally, [PLAGL2](/details-gene/5326) is involved in diverse biological processes, including the positive regulation of transcription, apoptosis, and post-embryonic development. Expression data indicates that **Overall**, [PLAGL2](/details-gene/5326) shows exceptionally high significance in [melanocyte of skin](/details-cell/CL1000458), suggesting it is a key determinant of this cell's identity. It is also significantly expressed in various neuronal populations, including [glutamatergic neuron](/details-cell/CL0000679) and [GABAergic neuron](/details-cell/CL0000617), as well as in myeloid progenitors and a range of epithelial cells, highlighting its broad importance across multiple lineages. ## Cellular Roles and Expression Landscape The expression profile of [PLAGL2](/details-gene/5326) reveals a pattern of high specificity in a few key cell types, alongside a broader, moderate-level significance across several developmental and functional lineages. **Overall**, the most striking feature is its exceptionally high cell significance index (CSI: 9.66) in [melanocyte of skin](/details-cell/CL1000458), establishing it as a principal marker for this cell type. This suggests a critical role in maintaining melanocyte identity, function, or survival. Following melanocytes, [PLAGL2](/details-gene/5326) demonstrates high significance in the nervous system, with strong expression in both [glutamatergic neuron](/details-cell/CL0000679) (CSI: 5.85) and [GABAergic neuron](/details-cell/CL0000617) (CSI: 4.09). This indicates its involvement in fundamental neuronal processes common to both excitatory and inhibitory neurons. The gene also plays a notable role in the myeloid lineage and hematopoietic stem cell populations. It is significantly expressed in [CD14-low, CD16-positive monocyte](/details-cell/CL0002396), [common myeloid progenitor](/details-cell/CL0000049), [myeloid leukocyte](/details-cell/CL0000766), and [promonocyte](/details-cell/CL0000559). Its presence in [stem cell](/details-cell/CL0000034) populations is consistent with its annotated function in post-embryonic development. Finally, [PLAGL2](/details-gene/5326) shows consistent significance across a diverse array of epithelial tissues, including in [ciliated epithelial cell](/details-cell/CL0000067), [intestinal epithelial cell](/details-cell/CL0002563), [colon epithelial cell](/details-cell/CL0011108), and [enterocyte](/details-cell/CL0000584). This broad but specific expression pattern suggests that [PLAGL2](/details-gene/5326) functions as a key transcriptional regulator maintaining specialized functions in terminally differentiated cells while also participating in the development of certain lineages. ## Pathways and Molecular Function Functionally, [PLAGL2](/details-gene/5326) is a sequence-specific DNA-binding transcription factor. Its primary molecular functions include [Dna-binding transcription activator activity, rna polymerase ii-specific](/details-go/GO:0001228) and [Dna-binding transcription factor activity, rna polymerase ii-specific](/details-go/GO:0000981), indicating it directly binds to DNA to initiate or enhance the transcription of target genes. This is supported by early research characterizing it as part of a family of transcriptional activators ([Link](https://doi.org/10.1074/jbc.273.36.23026)). Its localization is primarily within the [nucleus](/details-go/GO:0005634), which is consistent with its role as a transcription factor. At the biological process level, [PLAGL2](/details-gene/5326) is implicated in the [Positive regulation of transcription by rna polymerase ii](/details-go/GO:0045944) and [Post-embryonic development](/details-go/GO:0009791). This developmental role aligns with its expression in [stem cell](/details-cell/CL0000034) and [common myeloid progenitor](/details-cell/CL0000049). It is also involved in the [Positive regulation of intrinsic apoptotic signaling pathway](/details-go/GO:2001244), suggesting it may play a role in programmed cell death, a critical process in both development and tissue homeostasis. Interestingly, [PLAGL2](/details-gene/5326) is also annotated for involvement in [Lipid metabolic process](/details-go/GO:0006629) and [Chylomicron assembly](/details-go/GO:0034378). This functional link is highly consistent with its significant expression in [intestinal epithelial cell](/details-cell/CL0002563) and [enterocyte](/details-cell/CL0000584), cells that are central to the absorption of dietary lipids and their packaging into chylomicrons. ## Research Directions The expression and functional data for [PLAGL2](/details-gene/5326) point to several compelling areas for future investigation, particularly regarding its highly specific roles in certain cell types and its potential involvement in disease. **Proposed Hypotheses:** 1. Given its exceptionally high and specific significance score in [melanocyte of skin](/details-cell/CL1000458), [PLAGL2](/details-gene/5326) likely functions as a master regulator of melanogenesis or melanocyte survival. Its dysregulation may therefore be a key event in the pathogenesis of melanoma. 2. The functional annotation linking [PLAGL2](/details-gene/5326) to lipid metabolism, combined with its expression in [enterocyte](/details-cell/CL0000584)s, suggests it transcriptionally controls a network of genes essential for dietary fat absorption. Alterations in its activity could contribute to metabolic disorders related to lipid malabsorption. 3. Its role in positively regulating apoptosis and its expression in [common myeloid progenitor](/details-cell/CL0000049)s suggest that [PLAGL2](/details-gene/5326) is a critical checkpoint in myelopoiesis, ensuring the proper elimination of cells during differentiation. Loss of its function could potentially contribute to myeloproliferative neoplasms. **Key Experimental Approach:** To test the hypothesis that [PLAGL2](/details-gene/5326) is a master regulator in melanocytes (Hypothesis 1), a multi-faceted approach could be employed. First, CRISPR-Cas9-mediated knockout of [PLAGL2](/details-gene/5326) should be performed in primary human melanocytes and melanoma cell lines. The consequences of this knockout would be assessed by measuring changes in melanin content, cell proliferation rates, and susceptibility to apoptotic stimuli. Concurrently, chromatin immunoprecipitation sequencing (ChIP-seq) for [PLAGL2](/details-gene/5326) combined with RNA-sequencing of the knockout cells would identify its direct downstream target genes, thereby mapping its regulatory network and elucidating the specific pathways it controls (e.g., MITF signaling, tyrosinase production). **Therapeutic Potential:** As a transcription factor, [PLAGL2](/details-gene/5326) is a challenging direct target for small molecule inhibitors. However, its high specificity for certain cell types, particularly melanocytes, makes it an intriguing candidate for indirect therapeutic strategies. If it is established as an oncogenic driver in melanoma, targeting its crucial downstream effectors or its protein-protein interaction domains could prove to be a viable therapeutic avenue. Given its pro-apoptotic role, its function could be context-dependent, acting as either an oncogene or a tumor suppressor. Therefore, a therapeutic strategy of inhibition or activation would depend entirely on its specific role in the pathophysiology of a given disease.

Genular Protein ID: 548775206

Symbol: PLAL2_HUMAN

Name: Zinc finger protein PLAGL2

UniProtKB Accession Codes:

Q9UPG8 A8K8T5 E1P5M3 Q92584

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 1 GO 11 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 4 SIGNOR 1 SMART 1 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: 9722527

Title: Transcriptional activation capacity of the novel PLAG family of zinc finger proteins.

PubMed ID: 9722527

DOI: 10.1074/jbc.273.36.23026

PubMed ID: 8724849

Title: Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1.

PubMed ID: 8724849

DOI: 10.1093/dnares/3.1.17

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 11780052

Title: The DNA sequence and comparative analysis of human chromosome 20.

PubMed ID: 11780052

DOI: 10.1038/414865a

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: 496
  • Mass: 54584
  • Checksum: 20F5E7A28EF60603
  • Sequence:
    • MTTFFTSVPP WIQDAKQEEE VGWKLVPRPR GREAESQVKC QCEISGTPFS NGEKLRPHSL 
PQPEQRPYSC PQLHCGKAFA SKYKLYRHMA THSAQKPHQC MYCDKMFHRK DHLRNHLQTH 
DPNKEALHCS ECGKNYNTKL GYRRHLAMHA ASSGDLSCKV CLQTFESTQA LLEHLKAHSR 
RVAGGAKEKK HPCDHCDRRF YTRKDVRRHL VVHTGRKDFL CQYCAQRFGR KDHLTRHVKK 
SHSQELLKIK TEPVDMLGLL SCSSTVSVKE ELSPVLCMAS RDVMGTKAFP GMLPMGMYGA 
HIPTMPSTGV PHSLVHNTLP MGMSYPLESS PISSPAQLPP KYQLGSTSYL PDKLPKVEVD 
SFLAELPGSL SLSSAEPQPA SPQPAAAAAL LDEALLAKSP ANLSEALCAA NVDFSHLLGF 
LPLNLPPCNP PGATGGLVMG YSQAEAQPLL TTLQAQPQDS PGAGGPLNFG PLHSLPPVFT 
SGLSSTTLPR FHQAFQ