Details for: JAK3

Gene ID: 3718

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: JAK3

Ensembl ID: ENSG00000105639

Description: Janus kinase 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • helper T cell CL0000912
    CSI 10.43
    rCSI 14.75%
    PRS 64.3
  • promonocyte CL0000559
    CSI 8.12
    rCSI 13.92%
    PRS 67.33
  • activated type II NK T cell CL0000931
    CSI 6.21
    rCSI 6.99%
    PRS 74.67
  • common myeloid progenitor CL0000049
    CSI 5.94
    rCSI 4.8%
    PRS 59.64
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 5.43
    rCSI 4.91%
    PRS 55.12
  • CD4-positive, alpha-beta thymocyte CL0000810
    CSI 4.9
    rCSI 3.93%
    PRS 78.94
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 4.86
    rCSI 3.69%
    PRS 71.13
  • myeloid dendritic cell CL0000782
    CSI 4.34
    rCSI 6.28%
    PRS 74.25
  • alpha-beta T cell CL0000789
    CSI 4.29
    rCSI 5.02%
    PRS 74.7
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 3.86
    rCSI 2.77%
    PRS 72.56
  • mature alpha-beta T cell CL0000791
    CSI 3.79
    rCSI 13.73%
    PRS 77.81
  • hematopoietic stem cell CL0000037
    CSI 3.66
    rCSI 2.43%
    PRS 61.6
  • naive T cell CL0000898
    CSI 3.56
    rCSI 2.48%
    PRS 73.39
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 3.38
    rCSI 6.73%
    PRS 76.17
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 3.36
    rCSI 1.98%
    PRS 75.48
  • unswitched memory B cell CL0000970
    CSI 3.23
    rCSI 2.72%
    PRS 75.58
  • double negative thymocyte CL0002489
    CSI 3.21
    rCSI 2.23%
    PRS 69
  • mature T cell CL0002419
    CSI 2.81
    rCSI 2.19%
    PRS 76.18
  • T-helper 17 cell CL0000899
    CSI 2.77
    rCSI 2.2%
    PRS 79.93
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 2.7
    rCSI 13.53%
    PRS 70.73
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.69
    rCSI 1.81%
    PRS 71.23
  • Kupffer cell CL0000091
    CSI 2.61
    rCSI 5.96%
    PRS 58.17
  • class switched memory B cell CL0000972
    CSI 2.6
    rCSI 1.94%
    PRS 75.49
  • granulocyte CL0000094
    CSI 2.56
    rCSI 3.91%
    PRS 67.6
  • plasmablast CL0000980
    CSI 2.3
    rCSI 1.81%
    PRS 64.92
  • T follicular helper cell CL0002038
    CSI 2.25
    rCSI 1.69%
    PRS 73.31
  • blood vessel endothelial cell CL0000071
    CSI 2.2
    rCSI 4.57%
    PRS 55.62
  • early lymphoid progenitor CL0000936
    CSI 2.16
    rCSI 1.9%
    PRS 63.6
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 2.08
    rCSI 2.05%
    PRS 74.18
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.08
    rCSI 1.45%
    PRS 61.05
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 1.99
    rCSI 1.81%
    PRS 72.91
  • group 3 innate lymphoid cell CL0001071
    CSI 1.91
    rCSI 1.43%
    PRS 63.34
  • T-helper 1 cell CL0000545
    CSI 1.81
    rCSI 3.27%
    PRS 80.75
  • activated CD4-positive, alpha-beta T cell CL0000896
    CSI 1.8
    rCSI 1.67%
    PRS 77.96
  • mononuclear phagocyte CL0000113
    CSI 1.76
    rCSI 3.89%
    PRS 62.33
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 1.74
    rCSI 2.29%
    PRS 71.89
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 1.68
    rCSI 2%
    PRS 78.02
  • lymphoid lineage restricted progenitor cell CL0000838
    CSI 1.65
    rCSI 6.44%
    PRS 78.45
  • dendritic cell, human CL0001056
    CSI 1.57
    rCSI 2.41%
    PRS 67.03
  • common dendritic progenitor CL0001029
    CSI 1.42
    rCSI 1.78%
    PRS 68.72
  • innate lymphoid cell CL0001065
    CSI 1.36
    rCSI 2.82%
    PRS 60.79
  • granulocyte monocyte progenitor cell CL0000557
    CSI 1.19
    rCSI 1.03%
    PRS 63.23
  • mature B cell CL0000785
    CSI 1.19
    rCSI 1.03%
    PRS 68.83
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 1.05
    rCSI 3%
    PRS 77.82
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.04
    rCSI 1.27%
    PRS 46.91
  • memory T cell CL0000813
    CSI 1.04
    rCSI 2.01%
    PRS 84.73
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 0.95
    rCSI 0.73%
    PRS 58.46
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 0.93
    rCSI 1.59%
    PRS 76.69
  • Hofbauer cell CL3000001
    CSI 0.85
    rCSI 1.6%
    PRS 68.95
  • common lymphoid progenitor CL0000051
    CSI 0.81
    rCSI 1.09%
    PRS 79.77

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 [JAK3](/details-gene/3718) (Janus kinase 3) is a non-receptor tyrosine kinase that plays a pivotal role in intracellular signal transduction, particularly for cytokine receptors. It is a critical component of the JAK-STAT signaling pathway, which is essential for the development, differentiation, and function of immune cells. The expression profile of [JAK3](/details-gene/3718) is largely restricted to hematopoietic lineages, with exceptionally high significance observed in lymphoid cells, most notably [helper T cell](/details-cell/CL0000912). Mutations in [JAK3](/details-gene/3718) are associated with autosomal recessive severe combined immunodeficiency (SCID) ([600802](https://omim.org/entry/600802)), underscoring its indispensable role in establishing a functional adaptive immune system. ## Cellular Roles and Expression Landscape **Overall**, the expression landscape of [JAK3](/details-gene/3718) firmly establishes it as a cornerstone of the hematopoietic and immune systems. The gene exhibits its highest significance in lymphoid cells, including [helper T cell](/details-cell/CL0000912) (CSI: 10.43), [activated type II NK T cell](/details-cell/CL0000931), and various T cell subsets such as [CD4-positive, alpha-beta thymocyte](/details-cell/CL0000810) and [effector CD8-positive, alpha-beta T cell](/details-cell/CL0001050). This pattern highlights its central function in T cell and NK cell biology, consistent with its known role in transducing signals from cytokines essential for lymphocyte survival and proliferation [Link](https://doi.org/10.1038/370151a0). Beyond mature lymphocytes, [JAK3](/details-gene/3718) also shows significant expression in myeloid and progenitor cell populations. Its prominence in [promonocyte](/details-cell/CL0000559) (CSI: 8.12), [common myeloid progenitor](/details-cell/CL0000049), and [hematopoietic stem cell](/details-cell/CL0000037) suggests an important function during the early stages of hematopoiesis and myeloid lineage commitment. This broad but specific expression within the immune compartment makes [JAK3](/details-gene/3718) a key regulator of both innate and adaptive immunity, from the earliest progenitor stages to the effector functions of terminally differentiated cells. ## Pathways and Molecular Function The functional annotations for [JAK3](/details-gene/3718) confirm its identity as a central node in immune signaling. Its primary molecular function is [Protein tyrosine kinase activity](/details-cell/GO:0004713), enabling it to phosphorylate downstream targets, most notably STAT proteins ([Tyrosine phosphorylation of stat protein](/details-cell/GO:0007260)). This activity is integral to the [Cell surface receptor signaling pathway via jak-stat](/details-cell/GO:0007259). Biologically, [JAK3](/details-gene/3718) is deeply involved in processes governing both the [Adaptive immune response](/details-cell/GO:0002250) and the [Innate immune response](/details-cell/GO:0045087). Its function is critically dependent on signaling from common gamma-chain (γc) family cytokines. This is reflected in its association with numerous specific cytokine pathways, including [Interleukin-2-mediated signaling pathway](/details-cell/GO:0038110), [Interleukin-4-mediated signaling pathway](/details-cell/GO:0035771), [Interleukin-7-mediated signaling pathway](/details-cell/GO:0038111), and [Interleukin-15-mediated signaling pathway](/details-cell/GO:0035723). These pathways, curated in Reactome as [Signaling by interleukins](/details-cell/R-HSA-449147) and [Cytokine signaling in immune system](/details-cell/R-HSA-1280215), are fundamental for lymphocyte development, T cell homeostasis, and B cell differentiation. The requirement for [JAK3](/details-gene/3718) in mediating these signals is consistent with its high expression in T cells and their progenitors, cells that rely on IL-2 and IL-7 for their survival and expansion [Link](https://pubmed.ncbi.nlm.nih.gov/7662955/). ## Research Directions The specific and high-level expression of [JAK3](/details-gene/3718) within distinct immune cell populations provides a foundation for several testable hypotheses regarding its precise regulatory roles. 1. **Hypothesis 1:** Given the high significance of [JAK3](/details-gene/3718) in both lymphoid ([helper T cell](/details-cell/CL0000912)) and myeloid ([promonocyte](/details-cell/CL0000559)) lineages, it is hypothesized that the downstream consequences of JAK3 activation are highly context-dependent, shaped by cell-type-specific protein interactors and distinct chromatin landscapes, leading to divergent transcriptional programs from common cytokine signals. 2. **Hypothesis 2:** The significant expression of [JAK3](/details-gene/3718) in early hematopoietic progenitors, such as the [common myeloid progenitor](/details-cell/CL0000049), suggests that it plays a role in lineage fate decisions beyond its established functions in committed lymphocytes. It may act as a key mediator of cytokine signals that bias progenitor differentiation towards specific immune lineages. **Experimental Approach:** To test Hypothesis 1, one could employ a multi-omics strategy. Proximity-dependent biotinylation (e.g., TurboID) could be used to map the [JAK3](/details-gene/3718) interactome in primary human [helper T cell](/details-cell/CL0000912) versus monocyte-derived macrophages. Comparing the protein-protein interaction networks would reveal cell-type-specific binding partners. This could be integrated with phosphoproteomics and single-cell RNA-seq following stimulation with a common cytokine like IL-2 or IL-4 to correlate differential protein interactions with distinct downstream signaling cascades and transcriptional outputs. **Therapeutic Potential:** [JAK3](/details-gene/3718) is a validated and highly valuable therapeutic target. Its restricted expression to hematopoietic cells minimizes the potential for off-target effects in non-immune tissues, a significant advantage over inhibitors of more ubiquitously expressed JAK family members. Consequently, selective **inhibition** of [JAK3](/details-gene/3718) is an effective strategy for treating T-cell-driven autoimmune diseases, such as rheumatoid arthritis and psoriasis, by dampening pathological immune responses. However, as complete loss of function causes severe immunodeficiency ([600802](https://omim.org/entry/600802)), therapeutic intervention requires precise modulation to reduce hyper-inflammation without inducing broad immunosuppression.

Genular Protein ID: 959819075

Symbol: JAK3_HUMAN

Name: Janus kinase 3

UniProtKB Accession Codes:

P52333 Q13259 Q13260 Q13611 Q8N1E8 Q99699 Q9Y6S2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 3 CPTAC 2 CTD 1 ChEBI 7 ChEMBL 1 ComplexPortal 5 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 10 DrugCentral 1 EC 2 EMBL 9 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 45 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 17 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 41 PDBsum 41 PIR 1 PIRSF 1 PRINTS 3 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 5 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 11 RefSeq 1 Rhea 3 SIGNOR 1 SMART 3 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8022790

Title: Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes.

PubMed ID: 8022790

DOI: 10.1073/pnas.91.14.6374

PubMed ID: 7559633

Title: A kinase-deficient splice variant of the human JAK3 is expressed in hematopoietic and epithelial cancer cells.

PubMed ID: 7559633

DOI: 10.1074/jbc.270.42.25028

PubMed ID: 8921370

Title: Genomic sequence, organization, and chromosomal localization of human JAK3.

PubMed ID: 8921370

DOI: 10.1006/geno.1996.0520

PubMed ID: 15057824

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

PubMed ID: 15057824

DOI: 10.1038/nature02399

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: 8662778

Title: Expression of Janus kinase 3 in human endothelial and other non-lymphoid and non-myeloid cells.

PubMed ID: 8662778

DOI: 10.1074/jbc.271.24.13976

PubMed ID: 8022485

Title: Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2.

PubMed ID: 8022485

DOI: 10.1038/370151a0

PubMed ID: 7662955

Title: JAK3 protein tyrosine kinase mediates interleukin-7-induced activation of phosphatidylinositol-3' kinase.

PubMed ID: 7662955

PubMed ID: 7535338

Title: Regulation of JAK3 expression in human monocytes: phosphorylation in response to interleukins 2, 4, and 7.

PubMed ID: 7535338

DOI: 10.1084/jem.181.4.1425

PubMed ID: 10899310

Title: STAM2, a new member of the STAM family, binding to the Janus kinases.

PubMed ID: 10899310

DOI: 10.1016/s0014-5793(00)01760-9

PubMed ID: 12200137

Title: IL-2 receptor signaling through the Shb adapter protein in T and NK cells.

PubMed ID: 12200137

DOI: 10.1016/s0006-291x(02)02016-8

PubMed ID: 11909529

Title: The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3.

PubMed ID: 11909529

DOI: 10.1016/s0960-9822(02)00697-8

PubMed ID: 12351625

Title: The pseudokinase domain is required for suppression of basal activity of Jak2 and Jak3 tyrosine kinases and for cytokine-inducible activation of signal transduction.

PubMed ID: 12351625

DOI: 10.1074/jbc.m205156200

PubMed ID: 15121872

Title: Tyrosine 813 is a site of JAK2 autophosphorylation critical for activation of JAK2 by SH2-B beta.

PubMed ID: 15121872

DOI: 10.1128/mcb.24.10.4557-4570.2004

PubMed ID: 15592455

Title: Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.

PubMed ID: 15592455

DOI: 10.1038/nbt1046

PubMed ID: 18250158

Title: Phosphorylation of human Jak3 at tyrosines 904 and 939 positively regulates its activity.

PubMed ID: 18250158

DOI: 10.1128/mcb.01789-07

PubMed ID: 19290934

Title: Janus kinases in immune cell signaling.

PubMed ID: 19290934

DOI: 10.1111/j.1600-065x.2008.00754.x

PubMed ID: 19369195

Title: Large-scale proteomics analysis of the human kinome.

PubMed ID: 19369195

DOI: 10.1074/mcp.m800588-mcp200

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20440074

Title: IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac disease-associated inflammation and lymphomagenesis.

PubMed ID: 20440074

DOI: 10.1172/jci41344

PubMed ID: 15831699

Title: Crystal structure of the Jak3 kinase domain in complex with a staurosporine analog.

PubMed ID: 15831699

DOI: 10.1182/blood-2005-02-0707

PubMed ID: 7659163

Title: Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID).

PubMed ID: 7659163

DOI: 10.1038/377065a0

PubMed ID: 9354668

Title: Structural and functional basis for JAK3-deficient severe combined immunodeficiency.

PubMed ID: 9354668

PubMed ID: 9753072

Title: Molecular and biochemical characterization of JAK3 deficiency in a patient with severe combined immunodeficiency over 20 years after bone marrow transplantation: implications for treatment.

PubMed ID: 9753072

DOI: 10.1111/j.1365-2141.1998.tb08990.x

PubMed ID: 10982185

Title: Complete genomic organization of the human JAK3 gene and mutation analysis in severe combined immunodeficiency by single-strand conformation polymorphism.

PubMed ID: 10982185

DOI: 10.1007/s004390051012

PubMed ID: 14615376

Title: Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation.

PubMed ID: 14615376

DOI: 10.1182/blood-2003-06-2104

PubMed ID: 17344846

Title: Patterns of somatic mutation in human cancer genomes.

PubMed ID: 17344846

DOI: 10.1038/nature05610

Sequence Information:

  • Length: 1124
  • Mass: 125099
  • Checksum: 895D8563439B2B7C
  • Sequence:
    • MAPPSEETPL IPQRSCSLLS TEAGALHVLL PARGPGPPQR LSFSFGDHLA EDLCVQAAKA 
SGILPVYHSL FALATEDLSC WFPPSHIFSV EDASTQVLLY RIRFYFPNWF GLEKCHRFGL 
RKDLASAILD LPVLEHLFAQ HRSDLVSGRL PVGLSLKEQG ECLSLAVLDL ARMAREQAQR 
PGELLKTVSY KACLPPSLRD LIQGLSFVTR RRIRRTVRRA LRRVAACQAD RHSLMAKYIM 
DLERLDPAGA AETFHVGLPG ALGGHDGLGL LRVAGDGGIA WTQGEQEVLQ PFCDFPEIVD 
ISIKQAPRVG PAGEHRLVTV TRTDNQILEA EFPGLPEALS FVALVDGYFR LTTDSQHFFC 
KEVAPPRLLE EVAEQCHGPI TLDFAINKLK TGGSRPGSYV LRRSPQDFDS FLLTVCVQNP 
LGPDYKGCLI RRSPTGTFLL VGLSRPHSSL RELLATCWDG GLHVDGVAVT LTSCCIPRPK 
EKSNLIVVQR GHSPPTSSLV QPQSQYQLSQ MTFHKIPADS LEWHENLGHG SFTKIYRGCR 
HEVVDGEARK TEVLLKVMDA KHKNCMESFL EAASLMSQVS YRHLVLLHGV CMAGDSTMVQ 
EFVHLGAIDM YLRKRGHLVP ASWKLQVVKQ LAYALNYLED KGLPHGNVSA RKVLLAREGA 
DGSPPFIKLS DPGVSPAVLS LEMLTDRIPW VAPECLREAQ TLSLEADKWG FGATVWEVFS 
GVTMPISALD PAKKLQFYED RQQLPAPKWT ELALLIQQCM AYEPVQRPSF RAVIRDLNSL 
ISSDYELLSD PTPGALAPRD GLWNGAQLYA CQDPTIFEER HLKYISQLGK GNFGSVELCR 
YDPLGDNTGA LVAVKQLQHS GPDQQRDFQR EIQILKALHS DFIVKYRGVS YGPGRQSLRL 
VMEYLPSGCL RDFLQRHRAR LDASRLLLYS SQICKGMEYL GSRRCVHRDL AARNILVESE 
AHVKIADFGL AKLLPLDKDY YVVREPGQSP IFWYAPESLS DNIFSRQSDV WSFGVVLYEL 
FTYCDKSCSP SAEFLRMMGC ERDVPALCRL LELLEEGQRL PAPPACPAEV HELMKLCWAP 
SPQDRPSFSA LGPQLDMLWS GSRGCETHAF TAHPEGKHHS LSFS