Gene Name
JAK2
essential gene (from dbNSFP)
UniProt accession
O60674
Ensembl protein identifier
ENSP00000371067
Long Name
Janus kinase 2
Summary
This gene product is a protein tyrosine kinase involved in a specific subset of cytokine receptor signaling pathways. It has been found to be constituitively associated with the prolactin receptor and is required for responses to gamma interferon. Mice that do not express an active protein for this gene exhibit embryonic lethality associated with the absence of definitive erythropoiesis.
Kinase Group
Tyr: tyrosine protein kinase. (Log odds ratio: 0.628591)
FDA approved inhibitors
None found

GO terms

Gene Ontology - Biological Process Log-odds ratio
GO:0007498 mesoderm development 4.2083
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process 3.3019
GO:0050867 positive regulation of cell activation 2.9082
GO:0045597 positive regulation of cell differentiation 2.7947
GO:2001235 positive regulation of apoptotic signaling pathway 2.6705
GO:0042517 positive regulation of tyrosine phosphorylation of Stat3 protein 2.0196
GO:0045429 positive regulation of nitric oxide biosynthetic process 1.9844
GO:0042523 positive regulation of tyrosine phosphorylation of Stat5 protein 1.9707
GO:0008285 negative regulation of cell proliferation 1.8411
GO:0006979 response to oxidative stress 1.7704
GO:0030335 positive regulation of cell migration 1.752
GO:0008284 positive regulation of cell proliferation 1.7256
GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling 1.6576
GO:0016477 cell migration 1.6325
GO:0030218 erythrocyte differentiation 1.5784
GO:0030099 myeloid cell differentiation 1.5702
GO:0045944 positive regulation of transcription from RNA polymerase II promoter 1.4738
GO:0007186 G-protein coupled receptor signaling pathway 1.4402
GO:0007167 enzyme linked receptor protein signaling pathway 1.43
GO:0007259 JAK-STAT cascade 1.3858
GO:0045087 innate immune response 1.3607
GO:0042127 regulation of cell proliferation 1.3369
GO:0000186 activation of MAPKK activity 1.3347
GO:0043524 negative regulation of neuron apoptotic process 1.3269
GO:0018108 peptidyl-tyrosine phosphorylation 1.2044
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity 1.2021
GO:0042981 regulation of apoptotic process 1.1709
GO:0030154 cell differentiation 1.085
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation 0.8369
GO:0035556 intracellular signal transduction 0.7744
GO:0006928 movement of cell or subcellular component 0.7675
GO:0046777 protein autophosphorylation 0.6626
GO:0007165 signal transduction 0.6552
GO:0006915 apoptotic process 0.5959
GO:0043066 negative regulation of apoptotic process 0.4525
GO:0006468 protein phosphorylation 0.4403
GO:0097296 activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway 0.3858
GO:0061180 mammary gland epithelium development 0.3858
GO:0060399 positive regulation of growth hormone receptor signaling pathway 0.3858
GO:0042977 activation of JAK2 kinase activity 0.3858
GO:0042508 tyrosine phosphorylation of Stat1 protein 0.3858
GO:0035722 interleukin-12-mediated signaling pathway 0.3858
GO:0035409 histone H3-Y41 phosphorylation 0.3858
GO:0034050 host programmed cell death induced by symbiont 0.3858
GO:0033160 positive regulation of protein import into nucleus, translocation 0.3858
GO:0032731 positive regulation of interleukin-1 beta production 0.3858
GO:0031959 mineralocorticoid receptor signaling pathway 0.3858
GO:0031103 axon regeneration 0.3858
GO:0030041 actin filament polymerization 0.3858
GO:0045822 negative regulation of heart contraction 0.1634
GO:0042506 tyrosine phosphorylation of Stat5 protein 0.1634
GO:0010667 negative regulation of cardiac muscle cell apoptotic process 0.0
GO:0043392 negative regulation of DNA binding -0.0293
GO:0043388 positive regulation of DNA binding -0.0293
GO:0070671 response to interleukin-12 -0.1992
GO:0060396 growth hormone receptor signaling pathway -0.1992
GO:0033194 response to hydroperoxide -0.1992
GO:0032516 positive regulation of phosphoprotein phosphatase activity -0.2663
GO:0097191 extrinsic apoptotic signaling pathway -0.288
GO:0060334 regulation of interferon-gamma-mediated signaling pathway -0.3512
GO:0022408 negative regulation of cell-cell adhesion -0.3918
GO:0048008 platelet-derived growth factor receptor signaling pathway -0.5211
GO:0032024 positive regulation of insulin secretion -0.6142
GO:0043065 positive regulation of apoptotic process -0.6826
GO:0042503 tyrosine phosphorylation of Stat3 protein -0.7297
GO:0010811 positive regulation of cell-substrate adhesion -0.7297
GO:0007262 STAT protein import into nucleus -0.7297
GO:0050727 regulation of inflammatory response -0.8272
GO:0060397 JAK-STAT cascade involved in growth hormone signaling pathway -0.8366
GO:0046677 response to antibiotic -0.8366
GO:0032760 positive regulation of tumor necrosis factor production -0.8366
GO:0032496 response to lipopolysaccharide -0.918
GO:0051770 positive regulation of nitric-oxide synthase biosynthetic process -0.9362
GO:0007204 positive regulation of cytosolic calcium ion concentration -0.9362
GO:0033209 tumor necrosis factor-mediated signaling pathway -1.0293
GO:0019221 cytokine-mediated signaling pathway -1.059
GO:0007596 blood coagulation -1.0801
GO:0009755 hormone-mediated signaling pathway -1.2772
GO:0008631 intrinsic apoptotic signaling pathway in response to oxidative stress -1.2772
GO:0007260 tyrosine phosphorylation of STAT protein -1.3512
GO:0060333 interferon-gamma-mediated signaling pathway -1.4216
GO:0050729 positive regulation of inflammatory response -1.6142
GO:0034612 response to tumor necrosis factor -2.1167
GO:0006325 chromatin organization -2.8106
GO:0038083 peptidyl-tyrosine autophosphorylation -3.8996
GO:0071549 cellular response to dexamethasone stimulus -58.7575
GO:0071222 cellular response to lipopolysaccharide -60.3424
Gene Ontology - Molecular Function Log-odds ratio
GO:0042169 SH2 domain binding 2.4424
GO:0043560 insulin receptor substrate binding 2.2282
GO:0043548 phosphatidylinositol 3-kinase binding 2.2282
GO:0005102 receptor binding 1.0005
GO:0004715 non-membrane spanning protein tyrosine kinase activity 0.7458
GO:0004713 protein tyrosine kinase activity 0.592
GO:0035401 histone kinase activity (H3-Y41 specific) 0.3858
GO:0005143 interleukin-12 receptor binding 0.3858
GO:0005515 protein binding 0.2913
GO:0004672 protein kinase activity 0.0196
GO:0005524 ATP binding 0.0021
GO:0051428 peptide hormone receptor binding 0.0
GO:0033130 acetylcholine receptor binding 0.0
GO:0031702 type 1 angiotensin receptor binding 0.0
GO:0016772 transferase activity, transferring phosphorus-containing groups 0.0
GO:0019901 protein kinase binding -0.49
GO:0042393 histone binding -0.8366
GO:0020037 heme binding -1.0293
GO:0005131 growth hormone receptor binding -1.4216
GO:0008022 protein C-terminus binding -60.3424
Gene Ontology - Cellular Component Log-odds ratio
GO:0045121 membrane raft 2.6931
GO:0005901 caveola 2.6082
GO:0016020 membrane 1.2128
GO:0005634 nucleus 0.4352
GO:0031904 endosome lumen 0.3858
GO:0005829 cytosol 0.1546
GO:0005654 nucleoplasm -0.1796
GO:0016363 nuclear matrix -0.2663
GO:0005737 cytoplasm -0.355
GO:0005856 cytoskeleton -1.8789
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane -58.642

The JMOL viwer can load structure PDB files associated to that UniProt protein, as well as models provided by Interactome3D. The SVG image and the sequence scroller bellow correspond to the Ensembl protein associated with that UniProt: ENSP00000371067

In order to adress all inconsistencies between the sequences in UniProt, Ensembl, and UniProt, coordinate maps are built using Smith-Waterman pairwise alignment.

Mark
Clear
Align
ENSP00000371067 Low complexity (... SSF50729 SSF55550 Kinase-like_dom FERM_central Superfamily dom... Tyr_kinase_cat_dom Ser/Thr_dual-sp_kinase_dom SH2 Band_41_domain SMART domains Tyr_kinase_non-rcpt_Jak2 Ser-Thr/Tyr_kinase_cat_dom Tyr_kinase_non-rcpt_Jak/Tyk2 Prints domain SH2 Ser-Thr/Tyr_kinase_cat_dom Prot_kinase_dom Pfam domain FERM_domain SH2 Prot_kinase_dom PROSITE profiles Tyr_kinase_non-rcpt_Jak/Tyk2 PIRSF domain Sequence variant... COSMIC somatic ... 0 100 200 300 400 500 600 700 800 900 1000 0 1132 Scale bar Stop gained Frameshift variant Inframe insertion Missense variant Splice region variant Synonymous variant Insert Delete Variation Legend
MGMACLTMTEMEGTSTSSIYQNGDISGNANSMKQIDPVLQVYLYHSLGKSEADYLTFPSGEYVAEEICIAASKACGITPVYHNMFALMSETERIWYPPNHVFHIDESTRHNVLYRIRFYFPRWYCSGSNRAYRHGISRGAEAPLLDDFVMSYLFAQWRHDFVHGWIKVPVTHETQEECLGMAVLDMMRIAKENDQTPLAIYNSISYKTFLPKCIRAKIQDYHILTRKRIRYRFRRFIQQFSQCKATARNLKLKYLINLETLQSAFYTEKFEVKEPGSGPSGEEIFATIIITGNGGIQWSRGKHKESETLTEQDLQLYCDFPNIIDVSIKQANQEGSNESRVVTIHKQDGKNLEIELSSLREALSFVSLIDGYYRLTADAHHYLCKEVAPPAVLENIQSNCHGPISMDFAISKLKKAGNQTGLYVLRCSPKDFNKYFLTFAVERENVIEYKHCLITKNENEEYNLSGTKKNFSSLKDLLNCYQMETVRSDNIIFQFTKCCPPKPKDKSNLLVFRTNGVSDVPTSPTLQRPTHMNQMVFHKIRNEDLIFNESLGQGTFTKIFKGVRREVGDYGQLHETEVLLKVLDKAHRNYSESFFEAASMMSKLSHKHLVLNYGVCVCGDENILVQEFVKFGSLDTYLKKNKNCINILWKLEVAKQLAWAMHFLEENTLIHGNVCAKNILLIREEDRKTGNPPFIKLSDPGISITVLPKDILQERIPWVPPECIENPKNLNLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPKWAELANLINNCMDYEPDFRPSFRAIIRDLNSLFTPDYELLTENDMLPNMRIGALGFSGAFEDRDPTQFEERHLKFLQQLGKGNFGSVEMCRYDPLQDNTGEVVAVKKLQHSTEEHLRDFEREIEILKSLQHDNIVKYKGVCYSAGRRNLKLIMEYLPYGSLRDYLQKHKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKEYYKVKEPGESPIFWYAPESLTESKFSVASDVWSFGVVLYELFTYIEKSKSPPAEFMRMIGNDKQGQMIVFHLIELLKNNGRLPRPDGCPDEIYMIMTECWNNNVNQRPSFRDLALRVDQIRDNMAG* _________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________|_________| ________10________20________30________40________50________60________70________80________90_______100_______110_______120_______130_______140_______150_______160_______170_______180_______190_______200_______210_______220_______230_______240_______250_______260_______270_______280_______290_______300_______310_______320_______330_______340_______350_______360_______370_______380_______390_______400_______410_______420_______430_______440_______450_______460_______470_______480_______490_______500_______510_______520_______530_______540_______550_______560_______570_______580_______590_______600_______610_______620_______630_______640_______650_______660_______670_______680_______690_______700_______710_______720_______730_______740_______750_______760_______770_______780_______790_______800_______810_______820_______830_______840_______850_______860_______870_______880_______890_______900_______910_______920_______930_______940_______950_______960_______970_______980_______990______1000______1010______1020______1030______1040______1050______1060______1070______1080______1090______1100______1110______1120______1130

Scroll horizontaly across the sequence

The following information is extracted from Structure-PPi, a workflow for the annotation of protein residues. It finds features overlapping the variant or overlapping any residue that is in close physical proximity to the variant: 5 angstroms spatial distance or adjacent in the sequence if no PDB covers that area.

It may also report protein protein interfaces that might be affected by the variant, i.e. when they are at a distance of 8 angstroms from residues from a partner protein.

The structure PDB files used for these calculations are all those associated with the UniProt protein in UniProt and Interactome3D, which extends this set with models of single proteins and protein-protein interaction complexes. Pairwise alignment is used to resolve any sequence discrepancies.

The databases examined are UniProt, InterPro, COSMIC and Appris. The COSMIC database reports variants affecting that residue, not necessarily the same amino-acid change. Appris agglutinates features from FireDB, which are catalytic sites, and ligand-binding sites, and others such as trans-membrane domains, signal peptides, and ligand binding sites.

Structure-PPi A module for the annotation of cancer-related single-nucleotide variants at protein-protein interfaces. Miguel Vazquez, Alfonso Valencia, Tirso Pons. 2015. Bioinformatics. DOI: 10.1093/bioinformatics/btv142

KinMut Random Forest is a method specific for prediction of the pathogenicity of variants affecting the protein kinase superfamily. It characterizes the variants at the gene, domain and residue level with a combination of general and kinase-specific features. The pathogenicity of variants is evaluated by a random forest algorithm. Predictions are accompanied with a reliability score. Our approach outperforms available methods in a cross-validation experiment on the 3689 kinase variants in Uniprot. (Accuracy: 88.45%, Precision: 81.62%, recall: 75.22%, f-score: 78.29% and MCC: 0.68)

KinMut Random Forest
disease if score >0, neutral if score <0
Score
-0.889
Prediction
neutral

Group log-odds ratio
0.629
Kyte-Doolittle Hydrophobicity
-2.9
GO log-odds ratio
529
Volume
60.7
C-beta branching
0
Formal charge
1
FireDB residue
No
PhosphoELM residue
No
Uniprot residue
No
Active site
No
Binding
No
Carbohydrate
No
Disulfide
No
Metal
No
Modified residue
No
NP Binding
No
Repeat
No
Signal
No
Site
No
Trans-membrane
No
Zinc finger
No
Affected protein domains
Domain Log odds ratio
Protein_kinase 0.950917
Other predictors (dbNSFP)
SIFT
disease if score <0.05
Score
0.002
Prediction
disease
Polyphen2_HDIV
possible if >0.453, disease if >0.957
Score
1.0
Prediction
disease
Polyphen2_HVAR
possible if >0.447, disease if >0.909
Score
1.0
Prediction
disease
MutationTaster
disease if score >0.5
Score
0.999962
Prediction
disease
MutationAssessor
possible if >1.9, disease if >3.5
Score
2.16
Prediction
possible
FATHMM
disease if score <-1.5
Score
-1.52
Prediction
disease
VEST3
disease if score >0.8
Score
0.814
Prediction
disease
CADD
disease if score >3.5
Score
2.32891
Prediction
neutral
CADD Kircher (2014) Nature Genetics 46(3):310-5
FATHMM Shihab (2013) Human Mutation 34(1):57-65
VEST3 Carter (2013) BMC Genomics 14(3):1-16
Mutation Assessor Reva (2011) Nucleic Acids Research 1-14
Mutation Taster Schwarz (2014) Nature Methods 11, 361-362
Polyphen2 Adzhubei (2010) Nature Methods 7(4), 248-249
SIFT Ng (2001) Genome Research 11(45), 863-874
These literature co-mentions have been extracted automatically from the literature with iHop. Although it has proved to be a powerful guide to gather contextual information, manual inspection of these results might be required. Refer to Hoffmann and Valencia, 2004 for further details.

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