Details for: PPM1N

Gene ID: 147699

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: PPM1N

Ensembl ID: ENSG00000213889

Description: protein phosphatase, Mg2+/Mn2+ dependent 1N (putative)

Cell Significance Landscape

Associated with

Significant Cells

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

  • myeloid leukocyte CL0000766
    CSI 4.53
    rCSI 4.18%
    PRS 99.04
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 3.75
    rCSI 2.89%
    PRS 99.37
  • non-classical monocyte CL0000875
    CSI 3.38
    rCSI 5.41%
    PRS 98.68
  • epithelial cell of lower respiratory tract CL0002632
    CSI 3.36
    rCSI 2.61%
    PRS 99.19
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 3.21
    rCSI 4.21%
    PRS 99.65
  • extravillous trophoblast CL0008036
    CSI 3.13
    rCSI 3.87%
    PRS 97.83
  • neural progenitor cell CL0011020
    CSI 3.04
    rCSI 13.36%
    PRS 93.45
  • retinal rod cell CL0000604
    CSI 2.66
    rCSI 4.69%
    PRS 96.63
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.21
    rCSI 2.13%
    PRS 97.98
  • Langerhans cell CL0000453
    CSI 2.13
    rCSI 3.26%
    PRS 99.62
  • retinal cone cell CL0000573
    CSI 2.05
    rCSI 3.3%
    PRS 95.59
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 2.03
    rCSI 2.45%
    PRS 99.47

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 [PPM1N](/details-gene/147699) is a putative protein-coding gene located on chromosome 19q13.32, identified through large-scale sequencing efforts [Link](https://doi.org/10.1038/nature02399). It is predicted to encode a magnesium/manganese-dependent protein phosphatase. Functionally, [PPM1N](/details-gene/147699) is annotated with roles in [protein dephosphorylation](/details-go/GO:0006470) and the regulation of critical signaling pathways, including the canonical Wnt and NF-kappaB cascades. Expression data indicate that [PPM1N](/details-gene/147699) is a significant gene in cells of the myeloid lineage, including [myeloid leukocyte](/details-cell/CL0000766) and various monocyte subsets, suggesting a key role in innate immunity. Its expression in diverse non-immune cells, such as [epithelial cell of lower respiratory tract](/details-cell/CL0002632) and [neural progenitor cell](/details-cell/CL0011020), points towards broader, pleiotropic functions in tissue homeostasis and development. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [PPM1N](/details-gene/147699) highlights its prominent role within the myeloid compartment of the hematopoietic system. It shows high significance in [myeloid leukocyte](/details-cell/CL0000766) (CSI: 4.53) and is a key marker for several monocyte populations, including [CD14-low, CD16-positive monocyte](/details-cell/CL0002396) (CSI: 3.75), [non-classical monocyte](/details-cell/CL0000875) (CSI: 3.38), and [CD14-positive, CD16-positive monocyte](/details-cell/CL0002397) (CSI: 3.21). Its activity extends to professional antigen-presenting cells such as [Langerhans cell](/details-cell/CL0000453) and [CD1c-positive myeloid dendritic cell](/details-cell/CL0002399), suggesting its involvement in immune surveillance and response initiation. Beyond its role in immunity, [PPM1N](/details-gene/147699) is also significantly expressed in a variety of non-hematopoietic cell types. These include [epithelial cell of lower respiratory tract](/details-cell/CL0002632), [extravillous trophoblast](/details-cell/CL0008036) in the placenta, and [neural progenitor cell](/details-cell/CL0011020), indicating potential functions in tissue-specific processes like barrier function, embryonic development, and neurogenesis. Furthermore, its expression in specialized sensory cells like [retinal rod cell](/details-cell/CL0000604) and [retinal cone cell](/details-cell/CL0000573) suggests a functional role in the visual system. This broad but distinct expression pattern implies that [PPM1N](/details-gene/147699) may perform conserved molecular functions that are adapted to the specific needs of diverse cell lineages. ## Pathways and Molecular Function [PPM1N](/details-gene/147699) is predicted to function as a protein phosphatase with [protein serine/threonine phosphatase activity](/details-go/GO:0004722). This enzymatic function is dependent on divalent cations, as evidenced by its association with [magnesium ion binding](/details-go/GO:0000287) and [manganese ion binding](/details-go/GO:0030145). The gene's primary biological role appears to be the regulation of cellular signaling through [protein dephosphorylation](/details-go/GO:0006470). Its functional annotations specifically link it to two major signaling pathways: * **NF-kappaB Signaling:** The gene is implicated in the [regulation of canonical nf-kappab signal transduction](/details-go/GO:0043122). This is highly consistent with its strong expression in myeloid cells, where the NF-kappaB pathway is a master regulator of inflammation, cell survival, and immune responses. * **Wnt Signaling:** [PPM1N](/details-gene/147699) is also involved in the [positive regulation of canonical wnt signaling pathway](/details-go/GO:0090263). This pathway is fundamental to development, stem cell maintenance, and cell fate decisions, which aligns with the gene's expression in [neural progenitor cell](/details-cell/CL0011020) and [extravillous trophoblast](/details-cell/CL0008036). The protein product of [PPM1N](/details-gene/147699) is localized to both the [cytosol](/details-go/GO:0005829) and the [nucleus](/details-go/GO:0005634), enabling it to dephosphorylate a wide array of substrates and influence signaling events in multiple cellular compartments. ## Research Directions The functional annotations and cellular expression profile of [PPM1N](/details-gene/147699) suggest several avenues for future investigation. Its dual role in regulating the NF-kappaB and Wnt pathways in distinct cell types makes it a compelling subject for further study. **Testable Hypotheses:** 1. In myeloid cells, [PPM1N](/details-gene/147699) acts as a critical negative feedback regulator of inflammation by dephosphorylating and inactivating a key upstream kinase in the NF-kappaB pathway (e.g., IKKβ or TAK1), thereby dampening pro-inflammatory cytokine production following pathogenic challenge. 2. In [neural progenitor cell](/details-cell/CL0011020)s, [PPM1N](/details-gene/147699) promotes differentiation by dephosphorylating a repressive target in the Wnt signaling pathway, thus facilitating the expression of neurogenic transcription factors. **Proposed Experimental Approach:** To test the first hypothesis regarding the role of [PPM1N](/details-gene/147699) in regulating inflammation, a targeted gene knockout could be performed using CRISPR-Cas9 in a human monocyte cell line such as THP-1. Wild-type and [PPM1N](/details-gene/147699)-knockout cells would be stimulated with lipopolysaccharide (LPS). The consequences of [PPM1N](/details-gene/147699) loss on NF-kappaB signaling could be assessed by quantifying the phosphorylation status of key pathway components (e.g., IκBα, p65) via Western blot and by measuring the secretion of downstream cytokines like TNF-α and IL-6 using ELISA. An increase in both phosphorylation and cytokine levels in knockout cells would support its role as a negative regulator. **Therapeutic Potential:** As a phosphatase, [PPM1N](/details-gene/147699) is a potentially druggable enzyme. Its role in modulating the NF-kappaB pathway suggests it could be a target for inflammatory diseases. Small-molecule activators of [PPM1N](/details-gene/147699) could serve as a novel anti-inflammatory strategy. Conversely, its involvement in the Wnt pathway, which is often dysregulated in cancer, suggests that inhibitors of [PPM1N](/details-gene/147699) might have therapeutic value in specific oncological contexts. However, its expression across multiple important cell lineages, including immune, epithelial, and neural progenitors, indicates that systemic targeting could lead to significant off-target effects, suggesting a need for highly targeted delivery systems or cell-specific inhibitors.

Genular Protein ID: 2786816891

Symbol: PPM1N_HUMAN

Name: Probable protein phosphatase 1N

UniProtKB Accession Codes:

Q8N819 Q6P662

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 15 ChiTaRS 1 DEPOD 1 DMDM 1 DNASU 1 DisGeNET 1 EC 3 EMBL 5 Ensembl 4 ExpressionAtlas 1 GO 8 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 1 Rhea 6 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 430
  • Mass: 46170
  • Checksum: 297363BEB0E73F22
  • Sequence:
    • MAVLARQLQR LLWTACKKKE REKEGREEEE EEEAGRRAPE GPRSLLTAPR RAQRPHGGAE 
ASGGLRFGAS AAQGWRARME DAHCTWLSLP GLPPGWALFA VLDGHGGARA ARFGARHLPG 
HVLQELGPEP SEPEGVREAL RRAFLSADER LRSLWPRVET GGCTAVVLLV SPRFLYLAHC 
GDSRAVLSRA GAVAFSTEDH RPLRPRERER IHAAGGTIRR RRVEGSLAVS RALGDFTYKE 
APGRPPELQL VSAEPEVAAL ARQAEDEFML LASDGVWDTV SGAALAGLVA SRLRLGLAPE 
LLCAQLLDTC LCKGSLDNMT CILVCFPGAP RPSEEAIRRE LALDAALGCR IAELCASAQK 
PPSLNTVFRT LASEDIPDLP PGGGLDCKAT VIAEVYSQIC QVSEECGEKG QDGAGKSNPT 
HLGSALDMEA