Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Tyrosine-protein kinase JAK2  

UniProtKB / Swiss-Prot ID :  JAK2_HUMAN

Gene Name (Synonyms) : 
JAK2  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Endomembrane system; Peripheral membrane protein (By similarity). Cytoplasm. Nucleus. 

Protein Function :  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. Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. 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. Plays a role in cell cycle by phosphorylating CDKN1B. 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. 

Protein Sequence MGMACLTMTEMEGTSTSSIYQNGDISGNANSMKQIDPVLQVYLYHSLGKSEADYLTFPSGEYVAEEICIA...
Predicted Secondary Structure CCEEEEEEEECCCCCCCCCCCCCCCCCCCCCCCCCCCCEEEEEECCCCCCCCCEEEECCCCHHHHHHHHH...
Protein Variant
LocationDescription
127G -> D (in dbSNP:rs56118985). VAR_041716
191K -> Q (in an ovarian serous carcinomasample; somatic mutation).
346K -> R (in dbSNP:rs55667734). VAR_041718
377A -> E (in dbSNP:rs55953208). VAR_041719
393L -> V (in dbSNP:rs2230723). VAR_041720
537FHK -> L (in myeloproliferative disorderwith erythrocytosis).
538HK -> QL (in myeloproliferative disorderwith erythrocytosis).
539K -> L (in myeloproliferative disorderwith erythrocytosis; requires 2
584D -> E (in dbSNP:rs17490221). VAR_043129
607K -> N (in AML). VAR_032696
617V -> F (in PV, THCYT3 and AML; associatedwith susceptibility to Budd-Chiari
617V -> I (in THCYT3). VAR_067534
1063R -> H (in dbSNP:rs41316003). VAR_041721
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
201Phosphotyrosine (JAK2)PLAIYNSIS
HHHHHHHHH
9.39HPRD
Link-
206Phosphotyrosine (JAK2)NSISYKTFL
HHHHHHHCC
16.63HPRD
Link-
221PhosphotyrosineKIQDYHILT
HHHHCCCHH
3.71Phosphositeplus
Link-
221Phosphotyrosine (JAK2)KIQDYHILT
HHHHCCCHH
3.71HPRD
Link-
570PhosphotyrosineEVGDYGQLH
CCCCCCCCC
10.80PhosphoELM
Link-
570PhosphotyrosineEVGDYGQLH
CCCCCCCCC
10.80Phosphositeplus
Link-
570PhosphotyrosineEVGDYGQLH
CCCCCCCCC
10.80SysPTM
Link-
570Phosphotyrosine (JAK2)EVGDYGQLH
CCCCCCCCC
10.80HPRD
Link-
570Phosphotyrosine.EVGDYGQLH
CCCCCCCCC
10.80UniProtKB
Link-
790PhosphotyrosineNCMDYEPDF
HHHHCCHHH
11.50Phosphositeplus
Link-
813PhosphotyrosineFTPDYELLT
HCCCCCCCC
15.07PhosphoELM
Link-
813PhosphotyrosineFTPDYELLT
HCCCCCCCC
15.07Phosphositeplus
Link-
813Phosphotyrosine (JAK2)FTPDYELLT
HCCCCCCCC
15.07HPRD
Link-
931PhosphotyrosineLIMEYLPYG
EEEEECCCC
8.80Phosphositeplus
Link
956PhosphotyrosineKLLQYTSQI
HHHHHHHHH
14.34Phosphositeplus
Link
966PhosphotyrosineKGMEYLGTK
HHHHHHHHC
11.09Phosphositeplus
Link
1007DePhosphotyrosineQDKEYYKVK
CCCCEEEEE
17.83HPRD
Link
1007DePhosphotyrosineQDKEYYKVK
CCCCEEEEE
17.83HPRD
Link
1007PhosphotyrosineQDKEYYKVK
CCCCEEEEE
17.83Phosphositeplus
Link
1007Phosphotyrosine (ABL1)QDKEYYKVK
CCCCEEEEE
17.83HPRD
Link
1007Phosphotyrosine (JAK2)QDKEYYKVK
CCCCEEEEE
17.83HPRD
Link
1007Phosphotyrosine (JAK2)QDKEYYKVK
CCCCEEEEE
17.83PhosphoELM
Link
1007Phosphotyrosine; by autocatalysis.QDKEYYKVK
CCCCEEEEE
17.83UniProtKB
Link
1008DePhosphotyrosineDKEYYKVKE
CCCEEEEEC
15.47HPRD
Link
1008PhosphotyrosineDKEYYKVKE
CCCEEEEEC
15.47Phosphositeplus
Link
1008Phosphotyrosine (JAK2)DKEYYKVKE
CCCEEEEEC
15.47HPRD
Link
1008Phosphotyrosine (JAK2)DKEYYKVKE
CCCEEEEEC
15.47PhosphoELM
Link
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
EGFR_HUMANphysical interactionMINT-74562MINT16273093
BRCA1_HUMANphysical interactionMINT-13705MINT11163768
G3BP1_HUMANphysical interactionMINT-61281MINT15743820
STAT3_HUMANin vitro
in vivo
HPRD:00993HPRD10925297
11940572
11294897
10918587
12244095
11350938
12626508
8626374
12576423
14551213
AGTR1_HUMANin vivoHPRD:00993HPRD7746328
GRB2_HUMANin vivoHPRD:00993HPRD7500025
BRCA1_HUMANin vivoHPRD:00993HPRD11163768
CTLA4_HUMANin vivoHPRD:00993HPRD10842319
PPIA_HUMANin vivoHPRD:00993HPRD12668872
EGFR_HUMANin vitro
in vivo
HPRD:00993HPRD9363897
10635327
EPOR_HUMANin vitro
in vivo
HPRD:00993HPRD11779507
8343951
12441334
FYN_HUMANin vivoHPRD:00993HPRD10551884
CSF3R_HUMANin vitro
in vivo
HPRD:00993HPRD7775438
IL3RB_HUMANin vivoHPRD:00993HPRD10772872
INGR2_HUMANin vivoHPRD:00993HPRD7514165
JAK2_HUMANin vitro
in vivo
HPRD:00993HPRD9516124
9111318
11593427
15143187
11818507
7889566
15143188
15121872
17027227
RAF1_HUMANin vitro
in vivo
HPRD:00993HPRD8876196
10205168
9689060
11134016
STAT1_HUMANin vitro
in vivo
HPRD:00993HPRD7657660
11294897
10918587
15322115
7543024
11839738
12817007
7690989
12637327
11152457
CCR2_HUMANin vitro
in vivo
HPRD:00993HPRD9670957
STA5A_HUMANin vivoHPRD:00993HPRD9575217
8617237
7925280
11413148
GTF2I_HUMANin vitro
in vivo
HPRD:00993HPRD9837922
9012831
11373296
11313464
11934902
SHPS1_HUMANin vivoHPRD:00993HPRD10842184
INGR1_HUMANin vitro
in vivo
HPRD:00993HPRD7499845
11438544
PLCG2_HUMANin vivoHPRD:00993HPRD14978237
FES_HUMANin vivoHPRD:00993HPRD8631962
STA5B_HUMANin vivoHPRD:00993HPRD12538627
IRS1_HUMANin vivoHPRD:00993HPRD12960006
IRS2_HUMANin vivoHPRD:00993HPRD12960006
TPOR_HUMANin vitro
in vivo
HPRD:00993HPRD10979953
7534285
10224114
10918061
IKBA_HUMANin vitroHPRD:00993HPRD11493922
PGFRB_HUMANin vitro
in vivo
HPRD:00993HPRD8657151
9484840
IL3RA_HUMANin vivoHPRD:00993HPRD15988755
RON_HUMANin vivoHPRD:00993HPRD14982882
HES5_HUMANin vitro
in vivo
HPRD:00993HPRD15156153
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Disease Reference
Kegg disease
H00012 Polycythemia vera
OMIM disease
Note=Chromosomal aberrations involving JAK2 are found in both chronic and acute forms of eosinophilic, lymphoblastic and myeloid leukemia. Translocation t(8
9)(p22
p24) with PCM1 links the protein kinase domain of JAK2 to the major portion of PCM1. Translocation t(9
12)(p24
p13) with ETV6.
600880
263300Polycythemia vera (PV)
614521Thrombocythemia 3 (THCYT3)
254450Myelofibrosis (MYELOF)
601626Leukemia, acute myelogenous (AML)
Drug Reference
Kegg drug
D04696 Lestaurtinib (USAN/INN)
D08279 Tozasertib (USAN)
D08344 Tozasertib lactate (USAN); MK-0457
D09959 Ruxolitinib (USAN/INN)
D09960 Ruxolitinib phosphate (JAN/USAN); Jakafi (TN)
D10315 Momelotinib (USAN/INN)
D10358 Momelotinib dihydrochloride (USAN)
D10365 Gandotinib (USAN)
DrugBank
DB08877Ruxolitinib
DB08895Tofacitinib
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Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"Multiple reaction monitoring for robust quantitative proteomicanalysis of cellular signaling networks.";
Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M.;
Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-570, AND MASSSPECTROMETRY.
"The structural basis of Janus kinase 2 inhibition by a potent andspecific pan-Janus kinase inhibitor.";
Lucet I.S., Fantino E., Styles M., Bamert R., Patel O.,Broughton S.E., Walter M., Burns C.J., Treutlein H., Wilks A.F.,Rossjohn J.;
Blood 107:176-183(2006).
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 840-1132 IN COMPLEX WITHSYNTHETIC INHIBITOR, MASS SPECTROMETRY, AND PHOSPHORYLATION ATTYR-1007 AND TYR-1008.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures