Details for: DUSP14

Gene ID: 11072

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: DUSP14

Ensembl ID: ENSG00000276023

Description: dual specificity phosphatase 14

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • placental villous trophoblast CL2000060
    CSI 9.91
    rCSI 15.31%
    PRS 90.94
  • basal cell of prostate epithelium CL0002341
    CSI 6.6
    rCSI 19.11%
    PRS 94.24
  • squamous epithelial cell CL0000076
    CSI 5.03
    rCSI 11.94%
    PRS 89.71
  • luminal epithelial cell of mammary gland CL0002326
    CSI 4.75
    rCSI 8.64%
    PRS 96.18
  • granulocyte CL0000094
    CSI 3.88
    rCSI 5.93%
    PRS 95.78
  • ciliated epithelial cell CL0000067
    CSI 3.75
    rCSI 3.29%
    PRS 85
  • secretory cell CL0000151
    CSI 3.48
    rCSI 3.63%
    PRS 91.75
  • type B pancreatic cell CL0000169
    CSI 3.3
    rCSI 7.3%
    PRS 92.42
  • neural crest cell CL0011012
    CSI 3.26
    rCSI 2.57%
    PRS 86.87
  • deuterosomal cell CL4033044
    CSI 3.07
    rCSI 10.39%
    PRS 87.42
  • perivascular cell CL4033054
    CSI 3.05
    rCSI 4.17%
    PRS 95.02
  • interstitial cell of Cajal CL0002088
    CSI 3.01
    rCSI 3.84%
    PRS 95.22
  • keratinocyte CL0000312
    CSI 2.99
    rCSI 2.51%
    PRS 92.31
  • respiratory hillock cell CL4030023
    CSI 2.93
    rCSI 5.23%
    PRS 95.41
  • myofibroblast cell CL0000186
    CSI 2.92
    rCSI 4.04%
    PRS 89.75
  • basal-myoepithelial cell of mammary gland CL0002324
    CSI 2.87
    rCSI 5.43%
    PRS 96.68
  • conjunctival epithelial cell CL1000432
    CSI 2.84
    rCSI 4.34%
    PRS 91.66
  • CD8-positive, alpha-beta memory T cell CL0000909
    CSI 2.81
    rCSI 2.93%
    PRS 97.06
  • lung ciliated cell CL1000271
    CSI 2.74
    rCSI 3.17%
    PRS 87.99
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.73
    rCSI 2.12%
    PRS 94.47
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.73
    rCSI 3.5%
    PRS 89.33
  • multi-ciliated epithelial cell CL0005012
    CSI 2.65
    rCSI 2.64%
    PRS 87.63
  • ionocyte CL0005006
    CSI 2.59
    rCSI 2.78%
    PRS 93.57
  • stem cell CL0000034
    CSI 2.57
    rCSI 2.47%
    PRS 89.23
  • respiratory goblet cell CL0002370
    CSI 2.45
    rCSI 26.65%
    PRS 94.7
  • respiratory suprabasal cell CL4033048
    CSI 2.4
    rCSI 3.08%
    PRS 93.82
  • basal cell CL0000646
    CSI 2.34
    rCSI 3.13%
    PRS 90.1
  • ciliated cell CL0000064
    CSI 2.11
    rCSI 3.41%
    PRS 87.23
  • respiratory basal cell CL0002633
    CSI 2.1
    rCSI 2.18%
    PRS 93.85
  • extravillous trophoblast CL0008036
    CSI 2.06
    rCSI 2.55%
    PRS 91.19
  • radial glial cell CL0000681
    CSI 2.03
    rCSI 2.82%
    PRS 91.03
  • glandular epithelial cell CL0000150
    CSI 1.95
    rCSI 5.13%
    PRS 97.31
  • vascular associated smooth muscle cell CL0000359
    CSI 1.8
    rCSI 5.85%
    PRS 90.94
  • retinal rod cell CL0000604
    CSI 1.73
    rCSI 3.05%
    PRS 89.07
  • club cell CL0000158
    CSI 1.69
    rCSI 2.47%
    PRS 88.88
  • glioblast CL0000030
    CSI 1.68
    rCSI 2.68%
    PRS 86.09
  • fibroblast CL0000057
    CSI 1.5
    rCSI 4.3%
    PRS 83.6
  • chondrocyte CL0000138
    CSI 1.49
    rCSI 2.37%
    PRS 88.84
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.48
    rCSI 3.38%
    PRS 86.37
  • mammary gland epithelial cell CL0002327
    CSI 1.47
    rCSI 5.15%
    PRS 95.61
  • retinal cone cell CL0000573
    CSI 1.46
    rCSI 2.35%
    PRS 85.75
  • basal cell of epidermis CL0002187
    CSI 1.4
    rCSI 2.47%
    PRS 65.92
  • lung pericyte CL0009089
    CSI 1.22
    rCSI 3.21%
    PRS 95.69
  • luminal cell of prostate epithelium CL0002340
    CSI 0.95
    rCSI 5.08%
    PRS 95.47
  • podocyte CL0000653
    CSI 0.94
    rCSI 4.19%
    PRS 92.89
  • tracheobronchial serous cell CL0019001
    CSI 0.84
    rCSI 3.64%
    PRS 94.33
  • pancreatic stellate cell CL0002410
    CSI 0.71
    rCSI 4.13%
    PRS 93.73
  • direct pathway medium spiny neuron CL4023026
    CSI 0.53
    rCSI 12.75%
    PRS 79.62

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)

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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 [DUSP14](/details-gene/11072), or dual specificity phosphatase 14, is a protein-coding gene located on chromosome 17q12. It functions as a MAP kinase phosphatase, playing a key role in protein dephosphorylation. While research has highlighted its function as a negative regulator of T-cell receptor signaling ([Link](https://doi.org/10.4049/jimmunol.1300989)), expression data suggests a broader and highly significant role in various specialized epithelial and secretory cell types. **Overall**, it exhibits particularly high significance in [placental villous trophoblast](/details-cell/CL2000060) and [basal cell of prostate epithelium](/details-cell/CL0002341), indicating a crucial function in tissues characterized by high metabolic activity, proliferation, or specialized secretory functions. ## Cellular Roles and Expression Landscape The expression profile of [DUSP14](/details-gene/11072) suggests a prominent role in various epithelial and specialized cell types. **Overall**, the gene shows the highest significance in [placental villous trophoblast](/details-cell/CL2000060) (CSI: 9.91), a cell type critical for nutrient exchange and hormone production during pregnancy. This is followed by strong significance in [basal cell of prostate epithelium](/details-cell/CL0002341) (CSI: 6.60), [squamous epithelial cell](/details-cell/CL0000076) (CSI: 5.03), and [luminal epithelial cell of mammary gland](/details-cell/CL0002326) (CSI: 4.75), underscoring its potential involvement in the maintenance and function of these glandular and barrier tissues. While literature has focused on its role in immunity ([Link](https://doi.org/10.4049/jimmunol.166.1.197)), its significance in [granulocyte](/details-cell/CL0000094) (CSI: 3.88) is notable but less pronounced than in the top epithelial cell types. The gene's activity extends to other diverse cell populations, including [ciliated epithelial cell](/details-cell/CL0000067), [secretory cell](/details-cell/CL0000151), and [type B pancreatic cell](/details-cell/CL0000169), suggesting a widespread function in regulating cellular signaling across multiple organ systems. The presence in [keratinocyte](/details-cell/CL0000312) and [myofibroblast cell](/details-cell/CL0000186) further points to roles in tissue structure, repair, and homeostasis. ## Pathways and Molecular Function [DUSP14](/details-gene/11072) is primarily involved in protein dephosphorylation ([GO:0006470](https://www.ebi.ac.uk/QuickGO/term/GO:0006470)), a fundamental process for regulating protein activity and signal transduction. Its molecular function is characterized by its ability to act as a phosphatase on multiple substrates. It possesses Map kinase tyrosine/serine/threonine phosphatase activity ([GO:0017017](https://www.ebi.ac.uk/QuickGO/term/GO:0017017)), which is consistent with its role as a negative regulator of MAPK signaling pathways critical for cell growth, differentiation, and stress responses. Studies have confirmed this regulatory role in the immune system, where it is reported to negatively regulate T-cell receptor (TCR) signaling by inhibiting TAB1 activation ([Link](https://doi.org/10.4049/jimmunol.1300989)) and to provide negative-feedback regulation of CD28 costimulation ([Link](https://doi.org/10.4049/jimmunol.166.1.197)). Additionally, functional annotations suggest it may also have myosin phosphatase activity ([GO:0017018](https://www.ebi.ac.uk/QuickGO/term/GO:0017018)) and binding capabilities for both proteins ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)) and RNA ([GO:0003723](https://www.ebi.ac.uk/QuickGO/term/GO:0003723)), indicating a potential for broader and more complex cellular functions beyond MAPK regulation. ## Research Directions The contrast between the literature's focus on the immune role of [DUSP14](/details-gene/11072) and its high expression significance in epithelial tissues presents compelling avenues for future research. **Proposed Hypotheses:** 1. Given its high significance in proliferative tissues like the placenta and prostate basal cells, [DUSP14](/details-gene/11072) may function as a crucial homeostatic regulator, acting as a brake on MAPK-driven proliferation and differentiation to prevent uncontrolled cell growth in these hormonally-sensitive epithelial environments. 2. The function of [DUSP14](/details-gene/11072) may be highly context-dependent, where its primary role in epithelial cells is to maintain tissue homeostasis, while in immune cells, it is specifically upregulated upon activation to terminate inflammatory signals and prevent immunopathology. **Experimental Approach:** To test the hypothesis that [DUSP14](/details-gene/11072) regulates epithelial proliferation, a prostate organoid model could be employed. CRISPR-Cas9-mediated knockout of [DUSP14](/details-gene/11072) in primary human prostate epithelial cells would allow for the assessment of its role in a physiologically relevant 3D culture system. The growth rate, size, and cellular organization of knockout versus wild-type organoids could be monitored over time. Furthermore, phosphoproteomic analysis of these organoids would directly determine if loss of [DUSP14](/details-gene/11072) leads to hyper-activation of MAPK pathway components (e.g., phosphorylated ERK, JNK, p38), providing a mechanistic link between the phosphatase and the proliferative phenotype. **Therapeutic Potential:** As an enzyme that negatively regulates the MAPK pathway, [DUSP14](/details-gene/11072) could be a candidate for therapeutic modulation. Inhibition of [DUSP14](/details-gene/11072) might be explored as a strategy to sensitize certain tumors to MAPK-targeted therapies or to enhance immune responses by prolonging T-cell activation. However, the gene's high significance in multiple healthy epithelial tissues, such as the prostate and mammary gland, raises a significant concern for on-target, off-tumor toxicity. Any therapeutic strategy targeting [DUSP14](/details-gene/11072) would likely require a highly specific delivery mechanism or the development of allosteric modulators to avoid widespread systemic effects.

Genular Protein ID: 542709143

Symbol: DUS14_HUMAN

Name: Dual specificity protein phosphatase 14

UniProtKB Accession Codes:

O95147

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 12 ChEMBL 1 ChiTaRS 1 DEPOD 1 DNASU 1 DisGeNET 1 EC 4 EMBL 5 Ensembl 6 EvolutionaryTrace 1 ExpressionAtlas 1 GO 4 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRINTS 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 3 Rhea 9 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11123293

Title: Negative-feedback regulation of CD28 costimulation by a novel mitogen-activated protein kinase phosphatase, MKP6.

PubMed ID: 11123293

DOI: 10.4049/jimmunol.166.1.197

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: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 24403530

Title: Dual-specificity phosphatase 14 (DUSP14/MKP6) negatively regulates TCR signaling by inhibiting TAB1 activation.

PubMed ID: 24403530

DOI: 10.4049/jimmunol.1300989

PubMed ID: 19770498

Title: Overproduction, purification and structure determination of human dual-specificity phosphatase 14.

PubMed ID: 19770498

DOI: 10.1107/s0907444909023762

Sequence Information:

  • Length: 198
  • Mass: 22255
  • Checksum: 6AAFAE1B3A24F9AA
  • Sequence:
    • MSSRGHSTLP RTLMAPRMIS EGDIGGIAQI TSSLFLGRGS VASNRHLLQA RGITCIVNAT 
IEIPNFNWPQ FEYVKVPLAD MPHAPIGLYF DTVADKIHSV SRKHGATLVH CAAGVSRSAT 
LCIAYLMKFH NVCLLEAYNW VKARRPVIRP NVGFWRQLID YERQLFGKST VKMVQTPYGI 
VPDVYEKESR HLMPYWGI