Details for: MAP2K4

Gene ID: 6416

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: MAP2K4

Ensembl ID: ENSG00000065559

Description: mitogen-activated protein kinase kinase 4

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • VIP GABAergic cortical interneuron CL4023016
    CSI 43.58
    rCSI 52.06%
    PRS 31.31
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 43.2
    rCSI 53.74%
    PRS 29.83
  • sncg GABAergic cortical interneuron CL4023015
    CSI 36.99
    rCSI 59.49%
    PRS 33.54
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 36.65
    rCSI 61.51%
    PRS 31.46
  • sst GABAergic cortical interneuron CL4023017
    CSI 35.74
    rCSI 46.08%
    PRS 32.35
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 30.8
    rCSI 54.39%
    PRS 30.44
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 28.22
    rCSI 68.58%
    PRS 30.48
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 23.87
    rCSI 51.77%
    PRS 37.42
  • L6b glutamatergic cortical neuron CL4023038
    CSI 22.71
    rCSI 70.98%
    PRS 32.68
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 21.77
    rCSI 68.09%
    PRS 35.01
  • neuron CL0000540
    CSI 20.02
    rCSI 53.31%
    PRS 39.29
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 19.44
    rCSI 46.49%
    PRS 36.52
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 19.13
    rCSI 68.84%
    PRS 30.28
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 18.86
    rCSI 71.26%
    PRS 32.32
  • lung secretory cell CL1000272
    CSI 18.02
    rCSI 44.6%
    PRS 45.38
  • retinal ganglion cell CL0000740
    CSI 17.86
    rCSI 39.45%
    PRS 35.5
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 17.69
    rCSI 58.12%
    PRS 36.13
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 15.59
    rCSI 35.55%
    PRS 45.6
  • extravillous trophoblast CL0008036
    CSI 13.75
    rCSI 17.01%
    PRS 43.22
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 11.87
    rCSI 69.92%
    PRS 32.81
  • retinal bipolar neuron CL0000748
    CSI 11.6
    rCSI 21.73%
    PRS 37.1
  • naive B cell CL0000788
    CSI 10.74
    rCSI 9.21%
    PRS 55.93
  • Mueller cell CL0000636
    CSI 9.51
    rCSI 21.71%
    PRS 40.74
  • central nervous system neuron CL2000029
    CSI 9.41
    rCSI 69.19%
    PRS 35.36
  • cardiac endothelial cell CL0010008
    CSI 8.75
    rCSI 35.31%
    PRS 46.01
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 8.6
    rCSI 9.93%
    PRS 41.54
  • IgG plasma cell CL0000985
    CSI 8.59
    rCSI 10.29%
    PRS 66.26
  • glutamatergic neuron CL0000679
    CSI 8.42
    rCSI 17.29%
    PRS 41.05
  • ependymal cell CL0000065
    CSI 8.31
    rCSI 16.86%
    PRS 29.71
  • adipocyte CL0000136
    CSI 8.1
    rCSI 10.4%
    PRS 42.64
  • glioblast CL0000030
    CSI 7.98
    rCSI 12.73%
    PRS 41.05
  • secretory cell CL0000151
    CSI 7.94
    rCSI 8.29%
    PRS 47.93
  • intermediate monocyte CL0002393
    CSI 7.93
    rCSI 11.96%
    PRS 49.53
  • renal principal cell CL0005009
    CSI 7.82
    rCSI 20.3%
    PRS 52.42
  • GABAergic amacrine cell CL4030027
    CSI 7.73
    rCSI 26.47%
    PRS 38.53
  • conjunctival epithelial cell CL1000432
    CSI 7.58
    rCSI 11.58%
    PRS 47.89
  • corneal epithelial cell CL0000575
    CSI 7.35
    rCSI 21.01%
    PRS 63.77
  • radial glial cell CL0000681
    CSI 6.83
    rCSI 9.49%
    PRS 46.71
  • vascular leptomeningeal cell CL4023051
    CSI 6.5
    rCSI 11.4%
    PRS 39.72
  • respiratory basal cell CL0002633
    CSI 6.44
    rCSI 6.67%
    PRS 53.2
  • hepatic stellate cell CL0000632
    CSI 6.44
    rCSI 24.12%
    PRS 40.36
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 6.43
    rCSI 16.61%
    PRS 43.51
  • CD4-positive helper T cell CL0000492
    CSI 6.32
    rCSI 4.78%
    PRS 60.1
  • choroid plexus epithelial cell CL0000706
    CSI 5.82
    rCSI 9.52%
    PRS 37.94
  • retinal rod cell CL0000604
    CSI 5.75
    rCSI 10.13%
    PRS 45.62
  • blood vessel endothelial cell CL0000071
    CSI 5.58
    rCSI 11.58%
    PRS 45.32
  • cardiac neuron CL0010022
    CSI 5.38
    rCSI 17.22%
    PRS 44.5
  • neural crest cell CL0011012
    CSI 5.31
    rCSI 4.19%
    PRS 35.11
  • lung interstitial macrophage CL4033043
    CSI 5.25
    rCSI 11.79%
    PRS 67
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 5.16
    rCSI 6.62%
    PRS 45.27
  • rod bipolar cell CL0000751
    CSI 5.05
    rCSI 9.08%
    PRS 40.73
  • interneuron CL0000099
    CSI 5.03
    rCSI 10.1%
    PRS 37.17
  • medium spiny neuron CL1001474
    CSI 4.97
    rCSI 42.85%
    PRS 35.03
  • Kupffer cell CL0000091
    CSI 4.91
    rCSI 11.23%
    PRS 46.85
  • myeloid leukocyte CL0000766
    CSI 4.85
    rCSI 4.47%
    PRS 48.15
  • inhibitory interneuron CL0000498
    CSI 4.73
    rCSI 10.91%
    PRS 38.64
  • melanocyte CL0000148
    CSI 4.69
    rCSI 3.47%
    PRS 40.95
  • cerebral cortex endothelial cell CL1001602
    CSI 4.65
    rCSI 8.04%
    PRS 38.15
  • H1 horizontal cell CL0004217
    CSI 4.54
    rCSI 18%
    PRS 49.17
  • H2 horizontal cell CL0004218
    CSI 4.44
    rCSI 22.06%
    PRS 46.69
  • group 3 innate lymphoid cell CL0001071
    CSI 4.42
    rCSI 3.32%
    PRS 51.08
  • cerebral cortex neuron CL0010012
    CSI 4.35
    rCSI 17.72%
    PRS 44.32
  • brush cell of tracheobronchial tree CL0002075
    CSI 4.34
    rCSI 12.88%
    PRS 58.64
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 4.28
    rCSI 6.07%
    PRS 44.3
  • basal cell CL0000646
    CSI 4.24
    rCSI 5.67%
    PRS 48.67
  • fibroblast of lung CL0002553
    CSI 4.18
    rCSI 3.89%
    PRS 47.05
  • chondrocyte CL0000138
    CSI 4.17
    rCSI 6.63%
    PRS 40.37
  • luminal cell of prostate epithelium CL0002340
    CSI 4.11
    rCSI 22.12%
    PRS 62.3
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 4.07
    rCSI 4.92%
    PRS 55.31
  • mesothelial cell CL0000077
    CSI 3.99
    rCSI 15.62%
    PRS 24.61
  • epithelial cell of proximal tubule CL0002306
    CSI 3.97
    rCSI 9.69%
    PRS 42.97
  • Bergmann glial cell CL0000644
    CSI 3.96
    rCSI 5.41%
    PRS 43.39
  • GABAergic interneuron CL0011005
    CSI 3.95
    rCSI 62.35%
    PRS 51.99
  • pulmonary alveolar type 1 cell CL0002062
    CSI 3.84
    rCSI 22.16%
    PRS 48.94
  • goblet cell CL0000160
    CSI 3.71
    rCSI 3.51%
    PRS 48.11
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 3.68
    rCSI 3.35%
    PRS 62.32
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 3.56
    rCSI 9.29%
    PRS 46.69
  • oligodendrocyte precursor cell CL0002453
    CSI 3.55
    rCSI 7.81%
    PRS 32.25
  • pancreatic A cell CL0000171
    CSI 3.54
    rCSI 3.7%
    PRS 50.39
  • mononuclear phagocyte CL0000113
    CSI 3.4
    rCSI 7.49%
    PRS 51.38
  • alveolar adventitial fibroblast CL4028006
    CSI 3.4
    rCSI 5.37%
    PRS 48.53
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 3.34
    rCSI 10.3%
    PRS 59.02
  • fibroblast of cardiac tissue CL0002548
    CSI 3.29
    rCSI 15.76%
    PRS 46.28
  • retinal blood vessel endothelial cell CL0002585
    CSI 3.27
    rCSI 5.23%
    PRS 51.4
  • mucosal invariant T cell CL0000940
    CSI 3.23
    rCSI 2.61%
    PRS 57.87
  • ON parasol ganglion cell CL4033052
    CSI 3.21
    rCSI 45.58%
    PRS 39.61
  • cardiac muscle cell CL0000746
    CSI 3.19
    rCSI 4.57%
    PRS 38.55
  • cerebellar granule cell CL0001031
    CSI 3.17
    rCSI 4.66%
    PRS 42.74
  • Schwann cell CL0002573
    CSI 3.16
    rCSI 8.99%
    PRS 47.07
  • alveolar macrophage CL0000583
    CSI 3.1
    rCSI 5.11%
    PRS 52.83
  • intestinal crypt stem cell of colon CL0009043
    CSI 3.08
    rCSI 23.16%
    PRS 66.92
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 3.08
    rCSI 5.59%
    PRS 40.82
  • renal interstitial pericyte CL1001318
    CSI 3.01
    rCSI 8.31%
    PRS 44.02
  • direct pathway medium spiny neuron CL4023026
    CSI 3.01
    rCSI 72.13%
    PRS 30.94
  • ON midget ganglion cell CL4033046
    CSI 3.01
    rCSI 61.22%
    PRS 39.79
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.98
    rCSI 71.89%
    PRS 31.82
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.96
    rCSI 6.64%
    PRS 32.21
  • renal alpha-intercalated cell CL0005011
    CSI 2.95
    rCSI 3.95%
    PRS 55.8
  • OFF midget ganglion cell CL4033047
    CSI 2.88
    rCSI 58.64%
    PRS 41.02
  • stem cell CL0000034
    CSI 2.84
    rCSI 2.73%
    PRS 38.09
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.5
    rCSI 5.0%
    PRS 48.0%
  • myeloid dendritic cell CL0000782
    CSI 0.5
    rCSI 0.7%
    PRS 63.7%
  • type B pancreatic cell CL0000169
    CSI 0.5
    rCSI 1.2%
    PRS 44.8%
  • diffuse bipolar 4 cell CL4033031
    CSI 0.6
    rCSI 6.3%
    PRS 40.1%
  • neural progenitor cell CL0011020
    CSI 0.6
    rCSI 2.7%
    PRS 40.5%
  • diffuse bipolar 1 cell CL4033027
    CSI 0.6
    rCSI 4.8%
    PRS 42.4%
  • enteroglial cell CL4040002
    CSI 0.6
    rCSI 3.4%
    PRS 55.3%
  • flat midget bipolar cell CL4033033
    CSI 0.7
    rCSI 4.7%
    PRS 42.6%
  • regular ventricular cardiac myocyte CL0002131
    CSI 0.7
    rCSI 4.1%
    PRS 39.9%
  • innate lymphoid cell CL0001065
    CSI 0.7
    rCSI 1.4%
    PRS 52.8%
  • pancreatic ductal cell CL0002079
    CSI 0.7
    rCSI 1.4%
    PRS 49.5%
  • S cone cell CL0003050
    CSI 0.7
    rCSI 3.2%
    PRS 44.8%
  • glial cell CL0000125
    CSI 0.8
    rCSI 2.9%
    PRS 40.4%
  • stromal cell of ovary CL0002132
    CSI 0.8
    rCSI 2.2%
    PRS 62.6%
  • invaginating midget bipolar cell CL4033034
    CSI 0.8
    rCSI 4.7%
    PRS 44.3%
  • helper T cell CL0000912
    CSI 0.9
    rCSI 1.2%
    PRS 55.5%
  • squamous epithelial cell CL0000076
    CSI 0.9
    rCSI 2.1%
    PRS 52.9%
  • Hofbauer cell CL3000001
    CSI 0.9
    rCSI 1.7%
    PRS 57.7%
  • diffuse bipolar 2 cell CL4033028
    CSI 0.9
    rCSI 7.1%
    PRS 44.8%
  • keratocyte CL0002363
    CSI 0.9
    rCSI 2.3%
    PRS 57.3%
  • endothelial cell of placenta CL0009092
    CSI 0.9
    rCSI 4.7%
    PRS 59.2%
  • mesangial cell CL0000650
    CSI 1.0
    rCSI 3.9%
    PRS 58.5%
  • starburst amacrine cell CL0004232
    CSI 1.0
    rCSI 8.7%
    PRS 42.0%
  • pancreatic acinar cell CL0002064
    CSI 1.0
    rCSI 1.4%
    PRS 52.4%
  • diffuse bipolar 6 cell CL4033032
    CSI 1.1
    rCSI 5.5%
    PRS 44.0%
  • OFFx cell CL4033036
    CSI 1.1
    rCSI 5.2%
    PRS 44.6%
  • serotonergic neuron CL0000850
    CSI 1.1
    rCSI 4.9%
    PRS 33.4%
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 1.1
    rCSI 9.6%
    PRS 47.5%
  • glandular epithelial cell CL0000150
    CSI 1.1
    rCSI 2.9%
    PRS 69.5%
  • ciliated epithelial cell CL0000067
    CSI 1.2
    rCSI 1.0%
    PRS 36.5%
  • epicardial adipocyte CL1000309
    CSI 1.2
    rCSI 3.8%
    PRS 49.4%
  • paneth cell of epithelium of small intestine CL1000343
    CSI 1.2
    rCSI 3.3%
    PRS 61.6%
  • dendritic cell, human CL0001056
    CSI 1.3
    rCSI 2.0%
    PRS 54.6%
  • diffuse bipolar 3b cell CL4033030
    CSI 1.3
    rCSI 8.9%
    PRS 45.9%
  • lung ciliated cell CL1000271
    CSI 1.4
    rCSI 1.6%
    PRS 37.6%
  • amacrine cell CL0000561
    CSI 1.4
    rCSI 4.0%
    PRS 38.7%
  • macroglial cell CL0000126
    CSI 1.4
    rCSI 3.6%
    PRS 49.6%
  • regular atrial cardiac myocyte CL0002129
    CSI 1.4
    rCSI 4.5%
    PRS 46.5%
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.4
    rCSI 1.1%
    PRS 46.3%
  • colon macrophage CL0009038
    CSI 1.5
    rCSI 6.7%
    PRS 69.3%
  • tissue-resident macrophage CL0000864
    CSI 1.6
    rCSI 7.4%
    PRS 65.4%
  • centrilobular region hepatocyte CL0019029
    CSI 1.6
    rCSI 4.3%
    PRS 55.1%
  • keratinocyte CL0000312
    CSI 1.7
    rCSI 1.5%
    PRS 52.2%
  • retinal pigment epithelial cell CL0002586
    CSI 1.7
    rCSI 3.5%
    PRS 46.3%
  • stromal cell CL0000499
    CSI 1.8
    rCSI 4.9%
    PRS 46.8%
  • retinal cone cell CL0000573
    CSI 1.8
    rCSI 2.9%
    PRS 38.0%
  • GABAergic neuron CL0000617
    CSI 1.8
    rCSI 6.1%
    PRS 35.3%
  • suprabasal keratinocyte CL4033013
    CSI 1.8
    rCSI 3.0%
    PRS 25.0%
  • enteroendocrine cell of small intestine CL0009006
    CSI 1.8
    rCSI 4.1%
    PRS 61.9%
  • neuroendocrine cell CL0000165
    CSI 1.8
    rCSI 7.1%
    PRS 64.9%
  • placental villous trophoblast CL2000060
    CSI 1.9
    rCSI 2.9%
    PRS 45.1%
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.0
    rCSI 1.3%
    PRS 58.2%
  • respiratory suprabasal cell CL4033048
    CSI 2.0
    rCSI 2.6%
    PRS 52.2%
  • luminal epithelial cell of mammary gland CL0002326
    CSI 2.0
    rCSI 3.7%
    PRS 63.8%
  • small intestine goblet cell CL1000495
    CSI 2.1
    rCSI 4.5%
    PRS 57.0%
  • mesodermal cell CL0000222
    CSI 2.1
    rCSI 2.5%
    PRS 45.3%
  • tracheobronchial smooth muscle cell CL0019019
    CSI 2.1
    rCSI 3.6%
    PRS 55.7%
  • lung neuroendocrine cell CL1000223
    CSI 2.1
    rCSI 3.1%
    PRS 52.5%
  • ionocyte CL0005006
    CSI 2.1
    rCSI 2.3%
    PRS 45.5%
  • mucus secreting cell CL0000319
    CSI 2.1
    rCSI 3.4%
    PRS 58.3%
  • lung pericyte CL0009089
    CSI 2.1
    rCSI 5.6%
    PRS 55.2%
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 2.2
    rCSI 5.8%
    PRS 56.0%
  • parietal epithelial cell CL1000452
    CSI 2.2
    rCSI 5.8%
    PRS 40.1%
  • kidney connecting tubule epithelial cell CL1000768
    CSI 2.2
    rCSI 5.6%
    PRS 37.8%
  • midbrain dopaminergic neuron CL2000097
    CSI 2.2
    rCSI 14.3%
    PRS 52.7%
  • podocyte CL0000653
    CSI 2.2
    rCSI 9.9%
    PRS 46.2%
  • CD14-positive monocyte CL0001054
    CSI 2.2
    rCSI 2.8%
    PRS 58.6%
  • alveolar type 1 fibroblast cell CL4028004
    CSI 2.4
    rCSI 2.6%
    PRS 51.3%
  • blood vessel smooth muscle cell CL0019018
    CSI 2.4
    rCSI 19.5%
    PRS 41.8%
  • diffuse bipolar 3a cell CL4033029
    CSI 2.4
    rCSI 16.5%
    PRS 44.8%
  • retina horizontal cell CL0000745
    CSI 2.5
    rCSI 3.8%
    PRS 44.0%
  • renal beta-intercalated cell CL0002201
    CSI 2.5
    rCSI 5.9%
    PRS 49.4%
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.5
    rCSI 1.9%
    PRS 48.0%
  • duct epithelial cell CL0000068
    CSI 2.5
    rCSI 3.7%
    PRS 50.6%
  • adventitial cell CL0002503
    CSI 2.6
    rCSI 6.2%
    PRS 57.6%
  • BEST4+ enteroycte CL4030026
    CSI 2.6
    rCSI 3.3%
    PRS 50.0%
  • hepatocyte CL0000182
    CSI 2.7
    rCSI 4.8%
    PRS 45.9%
  • myoepithelial cell CL0000185
    CSI 2.7
    rCSI 6.8%
    PRS 55.8%
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 2.7
    rCSI 3.3%
    PRS 41.2%
  • multi-ciliated epithelial cell CL0005012
    CSI 2.7
    rCSI 2.7%
    PRS 41.5%
  • glycinergic amacrine cell CL4030028
    CSI 2.7
    rCSI 7.0%
    PRS 46.8%
  • elicited macrophage CL0000861
    CSI 2.7
    rCSI 2.5%
    PRS 55.0%
  • dopaminergic neuron CL0000700
    CSI 2.7
    rCSI 15.3%
    PRS 33.7%
  • endocardial cell CL0002350
    CSI 2.7
    rCSI 13.1%
    PRS 48.1%
  • pulmonary alveolar type 2 cell CL0002063
    CSI 2.8
    rCSI 4.3%
    PRS 56.8%
  • pancreatic D cell CL0000173
    CSI 2.8
    rCSI 2.7%
    PRS 49.8%
  • cerebral cortex pyramidal neuron CL4023111
    CSI 2.8
    rCSI 17.4%
    PRS 67.7%
  • stem cell CL0000034
    CSI 2.8
    rCSI 2.7%
    PRS 38.1%
  • OFF midget ganglion cell CL4033047
    CSI 2.9
    rCSI 58.6%
    PRS 41.0%
  • renal alpha-intercalated cell CL0005011
    CSI 3.0
    rCSI 4.0%
    PRS 55.8%
  • astrocyte of the cerebral cortex CL0002605
    CSI 3.0
    rCSI 6.6%
    PRS 32.2%
  • indirect pathway medium spiny neuron CL4023029
    CSI 3.0
    rCSI 71.9%
    PRS 31.8%
  • ON midget ganglion cell CL4033046
    CSI 3.0
    rCSI 61.2%
    PRS 39.8%
  • direct pathway medium spiny neuron CL4023026
    CSI 3.0
    rCSI 72.1%
    PRS 30.9%
  • renal interstitial pericyte CL1001318
    CSI 3.0
    rCSI 8.3%
    PRS 44.0%
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 3.1
    rCSI 5.6%
    PRS 40.8%
  • intestinal crypt stem cell of colon CL0009043
    CSI 3.1
    rCSI 23.2%
    PRS 66.9%
  • alveolar macrophage CL0000583
    CSI 3.1
    rCSI 5.1%
    PRS 52.8%
  • Schwann cell CL0002573
    CSI 3.2
    rCSI 9.0%
    PRS 47.1%
  • cerebellar granule cell CL0001031
    CSI 3.2
    rCSI 4.7%
    PRS 42.7%

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 [MAP2K4](/details-gene/6416) (mitogen-activated protein kinase kinase 4), also known as MKK4, is a protein-coding gene located on chromosome 17p12. It encodes a dual-specificity protein kinase that is a central component of the mitogen-activated protein kinase (MAPK) signaling cascade. As a key upstream activator, [MAP2K4](/details-gene/6416) phosphorylates and activates JNK-group MAP kinases and p38-group MAP kinases in response to environmental stresses and inflammatory cytokines [Link](https://doi.org/10.1126/science.7839144), [Link](https://doi.org/10.1126/science.7716521). **Overall**, expression data reveals its highest significance in the central nervous system, particularly within diverse subtypes of cortical interneurons and glutamatergic [neurons](/details-cell/CL0000540). Functionally, it is implicated in a wide range of cellular processes including stress response, apoptosis, immune signaling, and cellular senescence. Its role as a tumor suppressor gene has also been described in several carcinomas [Link](https://pubmed.ncbi.nlm.nih.gov/9622070/). ## Cellular Roles and Expression Landscape The **Overall** expression profile of [MAP2K4](/details-gene/6416) indicates a predominant and significant role within the central nervous system. The gene shows the highest cell significance index (CSI) in various classes of cortical interneurons, including [VIP GABAergic cortical interneurons](/details-cell/CL4023016) (CSI: 43.58), [pvalb GABAergic cortical interneurons](/details-cell/CL4023018) (CSI: 43.20), and [sncg GABAergic cortical interneurons](/details-cell/CL4023015) (CSI: 36.99). High significance is also observed in excitatory neuronal populations, such as [L2/3-6 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4023040) (CSI: 28.22), underscoring its broad importance in regulating cortical circuitry. This strong neuronal signature suggests that [MAP2K4](/details-gene/6416) is a crucial component of the intracellular signaling machinery that governs neuronal function, stress response, and survival. The notable, albeit lower, significance in [lung secretory cells](/details-cell/CL1000272) (CSI: 18.02) suggests its functional relevance may extend to epithelial tissues, potentially in response to environmental or inflammatory stimuli. The collective data portrays [MAP2K4](/details-gene/6416) as a highly active kinase in metabolically active cells, particularly those of the nervous system, where it likely integrates a wide array of extracellular signals into cellular responses. ## Pathways and Molecular Function [MAP2K4](/details-gene/6416) functions primarily as a dual-specificity protein kinase, possessing [protein serine/threonine kinase activity](/details-go/GO:0004674) and [protein tyrosine kinase activity](/details-go/GO:0004713). Its core function is the phosphorylation and activation of downstream kinases within the [Mapk cascade](/details-go/GO:0000165), most notably its specific role in the [Jnk cascade](/details-go/GO:0007254) as defined by its [Jun kinase kinase activity](/details-go/GO:0008545). Consistent with its role as a stress-activated kinase, [MAP2K4](/details-gene/6416) is a central node in numerous pathways related to cellular responses to external and internal insults. These include [Cellular responses to stress](/details-reactome/R-HSA-2262752), [Cellular senescence](/details-go/GO:0090398), and the [intrinsic apoptotic signaling pathway](/details-go/GO:0036481). Its involvement in the [positive regulation of neuron apoptotic process](/details-go/GO:0043525) is particularly relevant given its high expression in neuronal cell types. Furthermore, pathway analysis reveals an extensive role for [MAP2K4](/details-gene/6416) in the [Immune system](/details-reactome/R-HSA-168256). It is a key transducer in the [Innate immune system](/details-reactome/R-HSA-168249), participating in multiple [Toll-like receptor cascades](/details-reactome/R-HSA-168898), including those for [TLR2](/details-reactome/R-HSA-181438), [TLR3](/details-reactome/R-HSA-168164), and [TLR4](/details-reactome/R-HSA-166016). It also plays a role in [Cytokine signaling in immune system](/details-reactome/R-HSA-1280215), including [Interleukin-1 signaling](/details-reactome/R-HSA-9020702) and [Interleukin-17 signaling](/details-reactome/R-HSA-448424). This deep involvement in immune pathways, despite its primary expression signature in neurons, suggests a critical role in neuro-inflammation, where it may mediate the response of neurons to immune signals. ## Research Directions The data highlights a compelling duality for [MAP2K4](/details-gene/6416): its highest expression is in CNS neurons, yet its annotated functions are deeply intertwined with stress and innate immunity pathways typically associated with both immune cells and cellular stress responses. This suggests [MAP2K4](/details-gene/6416) may act as a crucial interface between the nervous and immune systems, particularly in the context of neuro-inflammatory diseases. **Proposed Hypotheses:** 1. [MAP2K4](/details-gene/6416) acts as a key mediator of neuronal stress and apoptosis in response to inflammatory signals from glial cells. Over-activation of this pathway in cortical neurons could contribute to the selective neuronal vulnerability observed in neurodegenerative disorders. 2. Within cortical interneurons, [MAP2K4](/details-gene/6416)-mediated signaling is essential for synaptic plasticity and network homeostasis under physiological conditions, but becomes maladaptive during chronic stress or inflammation, leading to circuit dysfunction. **Experimental Approach:** To test the hypothesis that [MAP2K4](/details-gene/6416) mediates neuronal response to inflammatory signals, one could utilize a neuron-microglia co-culture system. CRISPR/Cas9 could be used to specifically knock out [MAP2K4](/details-gene/6416) in primary cortical [neurons](/details-cell/CL0000540). These co-cultures could then be challenged with lipopolysaccharide (LPS) to activate microglial TLR4 signaling. The impact of [MAP2K4](/details-gene/6416) deletion on neuronal health could be assessed by measuring markers of apoptosis (e.g., cleaved caspase-3), changes in gene expression via single-cell RNA-sequencing, and alterations in neuronal function through electrophysiological recordings. This would directly test whether neuronal [MAP2K4](/details-gene/6416) is required to transduce inflammatory signals from glia into a pro-apoptotic neuronal response. **Therapeutic Potential:** The therapeutic potential of targeting [MAP2K4](/details-gene/6416) is context-dependent. In oncology, where it often acts as a tumor suppressor gene ([OMIM](/details-omim/601335)), therapeutic strategies might focus on reactivating its function or compensating for its loss. Conversely, in the context of neuro-inflammation or acute brain injury, where excessive JNK signaling can be excitotoxic and pro-apoptotic, [MAP2K4](/details-gene/6416) represents a candidate for **inhibition**. The development of specific, brain-penetrant small-molecule inhibitors targeting the kinase activity of [MAP2K4](/details-gene/6416) could be a neuroprotective strategy to mitigate damage following stroke or in chronic neurodegenerative diseases. However, the ubiquitous nature of MAP kinase signaling presents a significant challenge in avoiding off-target effects.

Genular Protein ID: 1176200165

Symbol: MP2K4_HUMAN

Name: Dual specificity mitogen-activated protein kinase kinase 4

UniProtKB Accession Codes:

Database IDs:

Citations:

PubMed ID: 7839144

Title: Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms.

PubMed ID: 7839144

DOI: 10.1126/science.7839144

PubMed ID: 7716521

Title: Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2.

PubMed ID: 7716521

DOI: 10.1126/science.7716521

PubMed ID: 9622070

Title: Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene.

PubMed ID: 9622070

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

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: 9003778

Title: MLK-3 activates the SAPK/JNK and p38/RK pathways via SEK1 and MKK3/6.

PubMed ID: 9003778

DOI: 10.1002/j.1460-2075.1996.tb01094.x

PubMed ID: 11104681

Title: Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor.

PubMed ID: 11104681

DOI: 10.1042/bj3520739

PubMed ID: 11090355

Title: Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3.

PubMed ID: 11090355

DOI: 10.1126/science.290.5496.1574

PubMed ID: 12189133

Title: Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway. A new mode of regulation of the MAP kinase cascade.

PubMed ID: 12189133

DOI: 10.1074/jbc.m202004200

PubMed ID: 12788955

Title: A docking site in MKK4 mediates high affinity binding to JNK MAPKs and competes with similar docking sites in JNK substrates.

PubMed ID: 12788955

DOI: 10.1074/jbc.m304229200

PubMed ID: 15866172

Title: Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases.

PubMed ID: 15866172

DOI: 10.1016/j.molcel.2005.04.001

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 19782076

Title: A scanning peptide array approach uncovers association sites within the JNK/beta arrestin signalling complex.

PubMed ID: 19782076

DOI: 10.1016/j.febslet.2009.09.035

PubMed ID: 17496909

Title: Differential regulation and properties of MAPKs.

PubMed ID: 17496909

DOI: 10.1038/sj.onc.1210392

PubMed ID: 19369195

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

PubMed ID: 19369195

DOI: 10.1074/mcp.m800588-mcp200

PubMed ID: 20801953

Title: Diverse physiological functions of MKK4 and MKK7 during early embryogenesis.

PubMed ID: 20801953

DOI: 10.1093/jb/mvq098

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21333379

Title: The bottleneck of JNK signaling: molecular and functional characteristics of MKK4 and MKK7.

PubMed ID: 21333379

DOI: 10.1016/j.ejcb.2010.11.008

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 24129315

Title: Immunoaffinity enrichment and mass spectrometry analysis of protein methylation.

PubMed ID: 24129315

DOI: 10.1074/mcp.o113.027870

PubMed ID: 20732303

Title: Crystal structures of MKK4 kinase domain reveal that substrate peptide binds to an allosteric site and induces an auto-inhibition state.

PubMed ID: 20732303

DOI: 10.1016/j.bbrc.2010.08.071

PubMed ID: 17344846

Title: Patterns of somatic mutation in human cancer genomes.

PubMed ID: 17344846

DOI: 10.1038/nature05610

Sequence Information:

  • Length: 399
  • Mass: 44288
  • Checksum: A472537F2F26770B
  • Sequence:
  • MAAPSPSGGG GSGGGSGSGT PGPVGSPAPG HPAVSSMQGK RKALKLNFAN PPFKSTARFT 
    LNPNPTGVQN PHIERLRTHS IESSGKLKIS PEQHWDFTAE DLKDLGEIGR GAYGSVNKMV 
    HKPSGQIMAV KRIRSTVDEK EQKQLLMDLD VVMRSSDCPY IVQFYGALFR EGDCWICMEL 
    MSTSFDKFYK YVYSVLDDVI PEEILGKITL ATVKALNHLK ENLKIIHRDI KPSNILLDRS 
    GNIKLCDFGI SGQLVDSIAK TRDAGCRPYM APERIDPSAS RQGYDVRSDV WSLGITLYEL 
    ATGRFPYPKW NSVFDQLTQV VKGDPPQLSN SEEREFSPSF INFVNLCLTK DESKRPKYKE 
    LLKHPFILMY EERAVEVACY VCKILDQMPA TPSSPMYVD