Summary of JAK2
In addition to modulating blood cell growth, JAK2 is somewhat involved in the immune system and therefore has been studied in relation to Crohn’s Disease and colon and rectal cancer [R].
Although not studied, this SNP is believed to play a part in illnesses caused by JAK2 protein mutations [R].
The Function of JAK2
Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins (PubMed:7615558). Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins (PubMed:9618263). Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B (PubMed:21423214). Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin (PubMed:19783980).
Recommended name:Tyrosine-protein kinase JAK2
Alternative name(s):Janus kinase 2
- RS10758669 (JAK2) ??
- RS10974944 (JAK2) ??
- RS12339666 (JAK2) ??
- RS12340895 (JAK2) ??
- RS2274471 (JAK2) ??
- RS36051895 (JAK2) ??
- RS3780374 (JAK2) ??
- RS75900472 (JAK2) ??
- RS77375493 (JAK2) ??
- RS7849191 (JAK2) ??
- RS9969783 (JAK2) ??
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Top Gene-Substance Interactions
JAK2 Interacts with These Diseases
Fix/Read: Natural STAT3 Inhibitors- What will inhibit STAT3, will also inhibit JAK2.They are part of the same pathway.
Substances That Increase JAK2
Substances That Decrease JAK2
The JAK2 gene is a part of the Janus Kinase family, which are involved in acquired autoimmune disorders and Crohn’s disease R
The JAK2 gene is associated with the prolactin receptor R
A variation of the JAK2 gene, known as the JAK2V617F mutation, causes the body to constantly produce red blood cells, white blood cells, and blood platelets R
JAK2 gene is mainly produced in bone marrow, where it acts like an On-Off switch, signaling when the body should start/stop producing RBCs, WBCs, and platelets R
The JAK2V617F mutation turns that On-Off switch to always On
This group of blood diseases is referred to as Myeloproliferative Neoplasms R
The JAK2 gene also influences immune cells that are directly associated with Crohn’s disease R
Crohn’s disease is categorized by chronic inflammation of the gut, possibly due to irregular immune response to bacteria in the gut R
White blood cells mistake normal gut bacteria, that aids in digestion, as dangerous and removes it, causing the gut to not properly digest food R
essential thrombocythemia Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic mutations in the JAK2 gene are associated with essential thrombocythemia, a disorder characterized by an increased number of platelets, the blood cells involved in normal blood clotting. The most common mutation (written as Val617Phe or V617F) replaces the protein building block (amino acid) valine with the amino acid phenylalanine at position 617 in the protein. This particular mutation is found in approximately half of people with essential thrombocythemia. A small number of affected individuals have a somatic mutation in another part of the JAK2 gene known as exon 12. The V617F JAK2 gene mutation results in the production of a JAK2 protein that is constantly turned on (constitutively activated), which, in essential thrombocythemia, leads to the overproduction of abnormal blood cells called megakaryocytes. Because platelets are formed from megakaryocytes, the overproduction of megakaryocytes results in an increased number of platelets. Excess platelets can cause abnormal blood clotting (thrombosis), which leads to many signs and symptoms of essential thrombocythemia. polycythemia vera Somatic mutations in the JAK2 gene are associated with polycythemia vera, a disorder characterized by uncontrolled blood cell production. The V617F mutation is found in approximately 96 percent of people with polycythemia vera. About 3 percent of affected individuals have a somatic mutation in the exon 12 region of the JAK2 gene. JAK2 gene mutations result in the production of a constitutively activated JAK2 protein, which seems to improve the survival of the cell and increase production of blood cells. With so many extra cells in the bloodstream, abnormal blood clots are more likely to form. In addition, the thicker blood flows more slowly throughout the body, which prevents organs from receiving enough oxygen. Many of the signs and symptoms of polycythemia vera are related to a lack of oxygen in body tissues. primary myelofibrosis Somatic JAK2 gene mutations are also associated with primary myelofibrosis, a condition in which bone marrow is replaced by scar tissue (fibrosis). The V617F mutation is found in approximately half of individuals with primary myelofibrosis. A small number of people with this condition have mutations in the exon 12 region of the gene. These JAK2 gene mutations result in a constitutively active JAK2 protein, which leads to the overproduction of abnormal megakaryocytes. These megakaryocytes stimulate other cells to release collagen, a protein that normally provides structural support for the cells in the bone marrow but causes scar tissue formation in primary myelofibrosis. Because of the fibrosis, the bone marrow cannot produce enough normal blood cells, leading to the signs and symptoms of the condition. other disorders Somatic JAK2 gene mutations are also associated with several related conditions. The V617F mutation is occasionally found in people with cancer of blood-forming cells (leukemia) or other bone marrow disorders. Budd-Chiari syndrome, which results from a blocked vein in the liver, can also be associated with the V617F mutation when it is caused by an underlying bone marrow disorder. It is unknown how one particular mutation can be associated with several conditions.
The JAK2 gene provides instructions for making a protein that promotes the growth and division (proliferation) of cells. This protein is part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from outside the cell to the cell's nucleus. The JAK2 protein is especially important for controlling the production of blood cells from hematopoietic stem cells. These stem cells are located within the bone marrow and have the potential to develop into red blood cells, white blood cells, and platelets.
Conditions with Increased Gene Activity
|Condition||Change (log2fold)||Comparison||Species||Experimental variables||Experiment name|
Conditions with Decreased Gene Activity
|Condition||Change (log2fold)||Comparison||Species||Experimental variables||Experiment name|
The following transcription factors affect gene expression:
Ubiquitously expressed throughout most tissues.
Regulated by autophosphorylation, can both activate or decrease activity (By similarity). Heme regulates its activity by enhancing the phosphorylation on Tyr-1007 and Tyr-1008.
Mn(2+) was used in the in vitro kinase assay but Mg(2+) is likely to be the in vivo cofactor.
- Protein Tyrosine Kinase Activity
- Non-Membrane Spanning Protein Tyrosine Kinase Activity
- Ras Guanyl-Nucleotide Exchange Factor Activity
- Receptor Binding
- Growth Hormone Receptor Binding
- Interleukin-12 Receptor Binding
- Atp Binding
- Protein Kinase Binding
- Heme Binding
- Histone Kinase Activity (H3-Y41 Specific)
- Sh2 Domain Binding
- Histone Binding
- Metal Ion Binding
- Mapk Cascade
- Activation Of Mapkk Activity
- Adaptive Immune Response
- Protein Phosphorylation
- Apoptotic Process
- Activation Of Cysteine-Type Endopeptidase Activity Involved In Apoptotic Process
- Movement Of Cell Or Subcellular Component
- Signal Transduction
- Enzyme Linked Receptor Protein Signaling Pathway
- G-Protein Coupled Receptor Signaling Pathway
- Positive Regulation Of Cytosolic Calcium Ion Concentration
- Jak-Stat Cascade
- Tyrosine Phosphorylation Of Stat Protein
- Stat Protein Import Into Nucleus
- Mesoderm Development
- Blood Coagulation
- Positive Regulation Of Cell Proliferation
- Negative Regulation Of Cell Proliferation
- Intrinsic Apoptotic Signaling Pathway In Response To Oxidative Stress
- Negative Regulation Of Cardiac Muscle Cell Apoptotic Process
- Positive Regulation Of Cell-Substrate Adhesion
- Positive Regulation Of Phosphatidylinositol 3-Kinase Signaling
- Peptidyl-Tyrosine Phosphorylation
- Cytokine-Mediated Signaling Pathway
- Negative Regulation Of Cell-Cell Adhesion
- Actin Filament Polymerization
- Cell Differentiation
- Erythrocyte Differentiation
- Positive Regulation Of Cell Migration
- Axon Regeneration
- Mineralocorticoid Receptor Signaling Pathway
- Positive Regulation Of Insulin Secretion
- Response To Lipopolysaccharide
- Positive Regulation Of Phosphoprotein Phosphatase Activity
- Positive Regulation Of Interleukin-1 Beta Production
- Positive Regulation Of Tumor Necrosis Factor Production
- Positive Regulation Of Protein Import Into Nucleus, Translocation
- Response To Hydroperoxide
- Tumor Necrosis Factor-Mediated Signaling Pathway
- Response To Tumor Necrosis Factor
- Histone H3-Y41 Phosphorylation
- Intracellular Signal Transduction
- Interleukin-12-Mediated Signaling Pathway
- Peptidyl-Tyrosine Autophosphorylation
- Regulation Of Cell Proliferation
- Tyrosine Phosphorylation Of Stat3 Protein
- Tyrosine Phosphorylation Of Stat5 Protein
- Tyrosine Phosphorylation Of Stat1 Protein
- Positive Regulation Of Tyrosine Phosphorylation Of Stat3 Protein
- Positive Regulation Of Tyrosine Phosphorylation Of Stat5 Protein
- Activation Of Jak2 Kinase Activity
- Regulation Of Apoptotic Process
- Positive Regulation Of Dna Binding
- Negative Regulation Of Dna Binding
- Negative Regulation Of Neuron Apoptotic Process
- Innate Immune Response
- Positive Regulation Of Nitric Oxide Biosynthetic Process
- Positive Regulation Of Cell Differentiation
- Negative Regulation Of Heart Contraction
- Response To Antibiotic
- Protein Autophosphorylation
- Platelet-Derived Growth Factor Receptor Signaling Pathway
- Regulation Of Inflammatory Response
- Positive Regulation Of Inflammatory Response
- Positive Regulation Of Peptidyl-Tyrosine Phosphorylation
- Positive Regulation Of Cell Activation
- Positive Regulation Of Sequence-Specific Dna Binding Transcription Factor Activity
- Positive Regulation Of Nitric-Oxide Synthase Biosynthetic Process
- Interferon-Gamma-Mediated Signaling Pathway
- Regulation Of Interferon-Gamma-Mediated Signaling Pathway
- Growth Hormone Receptor Signaling Pathway
- Jak-Stat Cascade Involved In Growth Hormone Signaling Pathway
- Positive Regulation Of Growth Hormone Receptor Signaling Pathway
- Mammary Gland Epithelium Development
- Response To Interleukin-12
- Extrinsic Apoptotic Signaling Pathway
- Activation Of Cysteine-Type Endopeptidase Activity Involved In Apoptotic Signaling Pathway
- Positive Regulation Of Growth Factor Dependent Skeletal Muscle Satellite Cell Proliferation
- Positive Regulation Of Epithelial Cell Apoptotic Process
- Positive Regulation Of Vascular Smooth Muscle Cell Proliferation