Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

JAK2 (O60674) - Overview - Molecular Target Synopsis


JAK2, Tyrosine-protein kinase JAK2
Enzyme Classification
UniProt O60674

Also Known as JAK2_HUMAN, 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. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). 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). Interacts with EPOR, LYN, SIRPA, SH2B1 and TEC (By similarity). Interacts with IL23R (PubMed:12023369). Interacts with SKB1 (PubMed:10531356). Interacts with STAM2 (PubMed:10899310). Interacts with IFNGR2 (via intracellular domain) (PubMed:7673114, PubMed:7615558). Interacts with LEPR (Isoform B) (By similarity). Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner (PubMed:20353823). Interacts with STRA6 (PubMed:21368206). Interacts with RHEX; this interaction occurs in a erythropoietin (EPO)-dependent manner (PubMed:25092874).

Inspect Structure
See all 3D Structures for JAK2

Isoforms / Transcripts (Protein Coding)

Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
1132ENSG00000096968ENST00000539801, ENST00000381652ENSP00000440387, ENSP00000371067O60674-1


JAK2 is targeted by Approved Drugs Tofacitinib, Baricitinib, Ruxolitinib. (see details)

Sub-cellular localization

UniProt: JAK2 is active in the following subcellular-locations: cytoplasm, endomembrane system, nucleus.
GO terms: JAK2 is active in the following subcellular-locations: caveola, cytoplasm, cytoskeleton, cytosol, endosome lumen, focal adhesion, glutamatergic synapse, membrane raft, nuclear matrix, nucleoplasm, nucleus, plasma membrane, postsynapse.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project JAK2 has gain in 8 cell-lines, loss in 12 cell-lines and no signal in 985 cell-lines. (see details)

Gene Expression

In NCI60, the highest expressing cell lines are: K_562, MCF7, SK_OV_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: OCI-M1, HEL, SET-2

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: K562, GM12878, CD14-positive monocyte

(see details)

RNA Interference

JAK2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SIHA, SCC90. (see details)

3D Structures

For JAK2 there are:
88 structures (141 chains) solved
84 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

JAK2 is solved in complex with the approved drug(s):


(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

JAK2 has been screened with 7393 compounds (9874 bioactivities), 4482 compounds have bioactivities that show binding affinity of <= 500nM (5540 bioactivities). (see details)