Details for: STK19

Gene ID: 8859

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: STK19

Ensembl ID: ENSG00000204344

Description: serine/threonine kinase 19

Cell Significance Landscape

Associated with

Significant Cells

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

  • chondrocyte CL0000138
    CSI 20.99
    rCSI 33.39%
    PRS 93.52
  • basal cell of epidermis CL0002187
    CSI 15.74
    rCSI 27.9%
    PRS 73.95
  • helper T cell CL0000912
    CSI 15.07
    rCSI 21.31%
    PRS 91.51
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 14.78
    rCSI 17.91%
    PRS 80.87
  • melanocyte of skin CL1000458
    CSI 13.68
    rCSI 18.64%
    PRS 74.34
  • suprabasal keratinocyte CL4033013
    CSI 11.69
    rCSI 19.08%
    PRS 74.4
  • innate lymphoid cell CL0001065
    CSI 6.48
    rCSI 13.37%
    PRS 90.73
  • placental villous trophoblast CL2000060
    CSI 5.23
    rCSI 8.08%
    PRS 94.93
  • mast cell CL0000097
    CSI 4.33
    rCSI 9.35%
    PRS 92.36
  • epithelial cell of proximal tubule CL0002306
    CSI 4.04
    rCSI 9.86%
    PRS 91.83
  • midzonal region hepatocyte CL0019028
    CSI 3.97
    rCSI 9.32%
    PRS 93.38
  • bronchus fibroblast of lung CL2000093
    CSI 3.76
    rCSI 3.05%
    PRS 96.13
  • regulatory T cell CL0000815
    CSI 3.75
    rCSI 4.35%
    PRS 90.27
  • perivascular cell CL4033054
    CSI 3.66
    rCSI 5%
    PRS 97.81
  • interstitial cell of Cajal CL0002088
    CSI 3.6
    rCSI 4.58%
    PRS 98
  • intestine goblet cell CL0019031
    CSI 3.56
    rCSI 3.16%
    PRS 94.7
  • multi-ciliated epithelial cell CL0005012
    CSI 3.56
    rCSI 3.55%
    PRS 92.49
  • epithelial cell of lung CL0000082
    CSI 3.48
    rCSI 2.88%
    PRS 97.08
  • duct epithelial cell CL0000068
    CSI 3.46
    rCSI 5.07%
    PRS 97.77
  • neural crest cell CL0011012
    CSI 3.38
    rCSI 2.67%
    PRS 93.11
  • mesodermal cell CL0000222
    CSI 3.34
    rCSI 4.01%
    PRS 96.31
  • cytotoxic T cell CL0000910
    CSI 3.16
    rCSI 18.11%
    PRS 93.38
  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.13
    rCSI 2.19%
    PRS 97.65
  • Mueller cell CL0000636
    CSI 3.07
    rCSI 7.01%
    PRS 92.53
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.99
    rCSI 2.31%
    PRS 97.97
  • ciliated epithelial cell CL0000067
    CSI 2.97
    rCSI 2.61%
    PRS 90.65
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.81
    rCSI 2.54%
    PRS 95.72
  • common myeloid progenitor CL0000049
    CSI 2.65
    rCSI 2.14%
    PRS 97.05
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.43
    rCSI 3.02%
    PRS 87.52
  • radial glial cell CL0000681
    CSI 2.4
    rCSI 3.34%
    PRS 95.42
  • enteric smooth muscle cell CL0002504
    CSI 2.35
    rCSI 3.35%
    PRS 96.4
  • peripheral nervous system neuron CL2000032
    CSI 2.34
    rCSI 3.19%
    PRS 92.52
  • ependymal cell CL0000065
    CSI 2.29
    rCSI 4.65%
    PRS 84.08
  • hepatocyte CL0000182
    CSI 2.24
    rCSI 4.02%
    PRS 94.52
  • lung ciliated cell CL1000271
    CSI 2.22
    rCSI 2.57%
    PRS 92.75
  • centrilobular region hepatocyte CL0019029
    CSI 2.18
    rCSI 5.68%
    PRS 92.53
  • type B pancreatic cell CL0000169
    CSI 2.07
    rCSI 4.58%
    PRS 95.99
  • alveolar adventitial fibroblast CL4028006
    CSI 2.04
    rCSI 3.22%
    PRS 97.04
  • mesenchymal cell CL0008019
    CSI 1.89
    rCSI 4.79%
    PRS 94.22
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.78
    rCSI 3.98%
    PRS 89.49

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 [STK19](/details-gene/8859), or Serine/Threonine Kinase 19, is a protein-coding gene located within the Major Histocompatibility Complex (MHC) class III region on chromosome 6. It encodes a nuclear kinase involved in fundamental cellular processes including [protein phosphorylation](/details-gene/GO:0006468) and [chromatin remodeling](/details-gene/GO:0006338). Expression data indicates that [STK19](/details-gene/8859) is a highly significant gene in diverse cell types, showing a particularly prominent role in [chondrocyte](/details-cell/CL0000138)s, various skin cells such as [basal cell of epidermis](/details-cell/CL0002187) and [melanocyte of skin](/details-cell/CL1000458), and multiple T lymphocyte populations, including [helper T cell](/details-cell/CL0000912)s. Its function has been linked to the regulation of Ras protein signaling, and its role in melanoma has been a subject of significant research and debate. ## Cellular Roles and Expression Landscape The expression profile of [STK19](/details-gene/8859) across a broad range of human cell types highlights its specialized functions in distinct cellular lineages. **Overall**, the gene's significance is most pronounced in three primary biological contexts: * **Connective and Skeletal Tissues:** The highest significance score for [STK19](/details-gene/8859) is observed in [chondrocyte](/details-cell/CL0000138) (CSI: 20.99), suggesting a critical function in cartilage maintenance and physiology. Its moderate expression in cells like [bronchus fibroblast of lung](/details-cell/CL2000093) (CSI: 3.76) further points towards a role in mesenchymal cell biology. * **Integumentary System:** [STK19](/details-gene/8859) is a key gene in the skin, with high significance in [basal cell of epidermis](/details-cell/CL0002187) (CSI: 15.74), [melanocyte of skin](/details-cell/CL1000458) (CSI: 13.68), and [suprabasal keratinocyte](/details-cell/CL4033013) (CSI: 11.69). This specific expression pattern in pigment-producing cells and keratinocytes is consistent with its investigated role in melanomagenesis. * **Immune System:** The gene is a significant marker within the adaptive immune system, particularly in T cells. It shows high CSI values in [helper T cell](/details-cell/CL0000912) (CSI: 15.07) and [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 14.78). Its presence is also noted in [regulatory T cell](/details-cell/CL0000815) (CSI: 3.75) and components of the innate immune system, such as [innate lymphoid cell](/details-cell/CL0001065) (CSI: 6.48) and [mast cell](/details-cell/CL0000097) (CSI: 4.33). The diverse cellular contexts in which [STK19](/details-gene/8859) is prominently expressed suggest it performs fundamental regulatory functions tailored to the specific needs of these specialized cell types. ## Pathways and Molecular Function Functionally, [STK19](/details-gene/8859) is a protein serine/threonine kinase ([GO:0004674](https://www.ebi.ac.uk/QuickGO/term/GO:0004674)) that utilizes [ATP binding](/details-gene/GO:0005524) to catalyze the phosphorylation of target proteins. Its localization to the [nucleus](/details-cell/GO:0005634) and [nuclear speck](/details-cell/GO:0016607)s places it in a prime position to regulate gene expression and nuclear architecture. Key annotated functions include: * **Chromatin Regulation:** [STK19](/details-gene/8859) has been shown to have [histone H2A.S1 kinase activity](/details-gene/GO:0044024), linking it directly to [chromatin remodeling](/details-gene/GO:0006338). This activity may be central to its role in establishing and maintaining cell-specific transcriptional programs in the diverse cell types where it is expressed, such as differentiating keratinocytes or memory T cells. * **Signal Transduction:** The gene is implicated in the [positive regulation of Ras protein signal transduction](/details-gene/GO:0046579). This connection is particularly relevant to its high expression in [melanocyte of skin](/details-cell/CL1000458), as NRAS is a key oncogenic driver in a subset of melanomas. Research has explored [STK19](/details-gene/8859) as a potential downstream effector or modulator in this pathway ([Link](https://doi.org/10.1016/j.cell.2019.01.002)). ## Research Directions The unique expression pattern and functional annotations of [STK19](/details-gene/8859) point to several compelling areas for future research. **Proposed Hypotheses:** 1. Given the contentious findings regarding its role in melanoma ([Link](https://doi.org/10.1016/j.cell.2019.01.002), [Link](https://doi.org/10.1016/j.cell.2020.04.014)), it is hypothesized that **[STK19](/details-gene/8859) is a context-dependent kinase in [melanocyte of skin](/details-cell/CL1000458)s, where its oncogenic potential is conditional upon the specific genetic background (e.g., NRAS mutation status) and the tumor microenvironment.** 2. The high significance of [STK19](/details-gene/8859) in both [helper T cell](/details-cell/CL0000912)s and memory CD8 T cells, combined with its role in chromatin remodeling, suggests that **[STK19](/details-gene/8859) acts as a critical epigenetic regulator that phosphorylates key chromatin-modifying enzymes or transcription factors to establish and maintain the transcriptional identity of T cell lineages during immune responses.** 3. The gene's top ranking in [chondrocyte](/details-cell/CL0000138)s suggests that **[STK19](/details-gene/8859) is essential for cartilage homeostasis, potentially by regulating signaling pathways that control chondrocyte proliferation, differentiation, or the expression of extracellular matrix components.** **Key Experimental Approach:** To test the hypothesis regarding its role in T cell differentiation (Hypothesis 2), a conditional knockout mouse model (*Stk19*fl/fl x *CD4-Cre*) could be employed. Naive CD4+ T cells from knockout and control animals would be isolated and subjected to *in vitro* differentiation protocols for Th1, Th2, and Th17 lineages. The success of differentiation would be quantified by intracellular cytokine staining and expression of master-regulator transcription factors via flow cytometry and RT-qPCR. To understand the underlying mechanism, phosphoproteomics could be performed on activated T cells to identify direct substrates of STK19, while ATAC-seq would reveal how its loss impacts chromatin accessibility at key T-cell-related gene loci. **Therapeutic Potential:** As a protein kinase, [STK19](/details-gene/8859) is a druggable enzyme. Its potential as a therapeutic target in NRAS-mutant melanoma remains an area of active investigation, and if validated, small molecule inhibitors of STK19 could offer a targeted treatment strategy. However, its high significance in multiple T cell subsets raises a critical concern: systemic inhibition of [STK19](/details-gene/8859) could lead to significant on-target immunomodulatory side effects, potentially compromising anti-tumor immunity or overall immune competence. Therefore, the therapeutic window for an STK19 inhibitor would need to be carefully evaluated, possibly exploring strategies like tumor-targeted delivery to mitigate systemic toxicity.

Genular Protein ID: 1867956435

Symbol: STK19_HUMAN

Name: N/A

UniProtKB Accession Codes:

P49842 A6NF95 A6NFW8 B0QZR5 Q13159 Q31617 Q5JP77 Q5ST72 Q5ST75

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 24 Ensembl 12 ExpressionAtlas 1 GO 7 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PIR 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 Pumba 1 RNAct 1 RefSeq 2 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8012361

Title: Characterisation of the novel gene G11 lying adjacent to the complement C4A gene in the human major histocompatibility complex.

PubMed ID: 8012361

DOI: 10.1093/hmg/3.3.481

PubMed ID: 8132574

Title: Structure and genetics of the partially duplicated gene RP located immediately upstream of the complement C4A and the C4B genes in the HLA class III region. Molecular cloning, exon-intron structure, composite retroposon, and breakpoint of gene duplication.

PubMed ID: 8132574

DOI: 10.1016/s0021-9258(17)37217-4

PubMed ID: 14656967

Title: Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse.

PubMed ID: 14656967

DOI: 10.1101/gr.1736803

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 8575831

Title: Complete sequence of the complement C4 gene from the HLA-A1, B8, C4AQ0, C4B1, DR3 haplotype.

PubMed ID: 8575831

DOI: 10.1007/bf00587313

PubMed ID: 9812991

Title: The G11 gene located in the major histocompatibility complex encodes a novel nuclear serine/threonine protein kinase.

PubMed ID: 9812991

DOI: 10.1074/jbc.273.47.30954

PubMed ID: 30712867

Title: Pharmacological targeting of STK19 inhibits oncogenic NRAS-driven melanomagenesis.

PubMed ID: 30712867

DOI: 10.1016/j.cell.2019.01.002

PubMed ID: 32531245

Title: Evidence That STK19 Is Not an NRAS-dependent Melanoma Driver.

PubMed ID: 32531245

DOI: 10.1016/j.cell.2020.04.014

PubMed ID: 32531246

Title: A Reply to ''Evidence that STK19 Is Not an NRAS-Dependent Melanoma Driver''.

PubMed ID: 32531246

DOI: 10.1016/j.cell.2020.04.029

PubMed ID: 17344846

Title: Patterns of somatic mutation in human cancer genomes.

PubMed ID: 17344846

DOI: 10.1038/nature05610

Sequence Information:

  • Length: 254
  • Mass: 28465
  • Checksum: 1B3800438D9DD5A9
  • Sequence:
    • MSWKRHHLIP ETFGVKRRRK RGPVESDPLR GEPGSARAAV SELMQLFPRG LFEDALPPIV 
LRSQVYSLVP DRTVADRQLK ELQEQGEIRI VQLGFDLDAH GIIFTEDYRT RVLKACDGRP 
YAGAVQKFLA SVLPACGDLS FQQDQMTQTF GFRDSEITHL VNAGVLTVRD AGSWWLAVPG 
AGRFIKYFVK GRQAVLSMVR KAKYRELLLS ELLGRRAPVV VRLGLTYHVH DLIGAQLVDC 
ISTTSGTLLR LPET

Genular Protein ID: 2661290453

Symbol: A0A1U9X8L3_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A1U9X8L3

Database IDs:

AlphaFoldDB 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 3 InterPro 1 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 Pfam 1 RefSeq 1 SAM 1 SMR 1 VEuPathDB 1

Sequence Information:

  • Length: 364
  • Mass: 40495
  • Checksum: B904F6999B7C533E
  • Sequence:
    • MQKWFSAFDD AIIQRQWRAN PSRGGGGVSF TKEVDTNVAT GAPPRRQRVP GRACPWREPI 
RGRRGARPGG GDAGGTPGET VRHCSAPEDP IFRFSSLHSY PFPGTIKSRD MSWKRHHLIP 
ETFGVKRRRK RGPVESDPLR GEPGSARAAV SELMQLFPRG LFEDALPPIV LRSQVYSLVP 
DRTVADRQLK ELQEQGEIRI VQLGFDLDAH GIIFTEDYRT RVLKACDGRP YAGAVQKFLA 
SVLPACGDLS FQQDQMTQTF GFRDSEITHL VNAGVLTVRD AGSWWLAVPG AGRFIKYFVK 
GRQAVLSMVR KAKYRELLLS ELLGRRAPVV VRLGLTYHVH DLIGAQLVDC ISTTSGTLLR 
LPET