Details for: NAE1

Gene ID: 8883

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: NAE1

Ensembl ID: ENSG00000159593

Description: NEDD8 activating enzyme E1 subunit 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • plasmacytoid dendritic cell, human CL0001058
    CSI 14.97
    rCSI 10.45%
    PRS 35.23
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 13.25
    rCSI 22.24%
    PRS 21.31
  • mucus secreting cell CL0000319
    CSI 12.41
    rCSI 19.71%
    PRS 42.7
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 9.83
    rCSI 11.35%
    PRS 29.4
  • multi-ciliated epithelial cell CL0005012
    CSI 8.52
    rCSI 8.51%
    PRS 28.89
  • tracheobronchial smooth muscle cell CL0019019
    CSI 7.71
    rCSI 13.6%
    PRS 41.75
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 6.79
    rCSI 21.23%
    PRS 24.13
  • sncg GABAergic cortical interneuron CL4023015
    CSI 6.45
    rCSI 10.37%
    PRS 23.14
  • Bergmann glial cell CL0000644
    CSI 5.98
    rCSI 8.18%
    PRS 32.07
  • BEST4+ enteroycte CL4030026
    CSI 5.83
    rCSI 7.25%
    PRS 35.9
  • regular ventricular cardiac myocyte CL0002131
    CSI 5.65
    rCSI 35.31%
    PRS 27.72
  • Schwann cell CL0002573
    CSI 5.58
    rCSI 15.87%
    PRS 35.02
  • kidney connecting tubule epithelial cell CL1000768
    CSI 5.41
    rCSI 13.72%
    PRS 26.28
  • mature alpha-beta T cell CL0000791
    CSI 5.37
    rCSI 19.45%
    PRS 51.65
  • alpha-beta T cell CL0000789
    CSI 5.15
    rCSI 6.03%
    PRS 46.64
  • retina horizontal cell CL0000745
    CSI 4.99
    rCSI 7.61%
    PRS 31.16
  • placental villous trophoblast CL2000060
    CSI 4.89
    rCSI 7.55%
    PRS 31.84
  • CD4-positive, alpha-beta thymocyte CL0000810
    CSI 4.54
    rCSI 3.64%
    PRS 54.02
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 4.39
    rCSI 16.61%
    PRS 22.16
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 4.28
    rCSI 4.36%
    PRS 45.39
  • fallopian tube secretory epithelial cell CL4030006
    CSI 4.2
    rCSI 4.04%
    PRS 34.41
  • neural progenitor cell CL0011020
    CSI 4.18
    rCSI 18.4%
    PRS 29.13
  • erythroid progenitor cell CL0000038
    CSI 4.05
    rCSI 23.21%
    PRS 44.78
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 3.98
    rCSI 3.03%
    PRS 43.18
  • ciliated cell CL0000064
    CSI 3.81
    rCSI 6.18%
    PRS 32.92
  • CD4-positive, alpha-beta cytotoxic T cell CL0000934
    CSI 3.7
    rCSI 5.08%
    PRS 54.29
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 3.46
    rCSI 2.67%
    PRS 32
  • mesenchymal cell CL0008019
    CSI 3.37
    rCSI 8.56%
    PRS 31.48
  • myoepithelial cell CL0000185
    CSI 3.31
    rCSI 8.39%
    PRS 40.74
  • astrocyte of the cerebral cortex CL0002605
    CSI 3.23
    rCSI 7.24%
    PRS 21.89
  • club cell CL0000158
    CSI 3.15
    rCSI 4.62%
    PRS 35.17
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 3.12
    rCSI 9.22%
    PRS 38.14
  • class switched memory B cell CL0000972
    CSI 3.06
    rCSI 2.28%
    PRS 51.37
  • perivascular cell CL4033054
    CSI 3.05
    rCSI 4.17%
    PRS 37.5
  • mature T cell CL0002419
    CSI 2.89
    rCSI 2.24%
    PRS 48.17
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.86
    rCSI 3.69%
    PRS 22.04
  • naive T cell CL0000898
    CSI 2.81
    rCSI 1.96%
    PRS 45.07
  • myeloid leukocyte CL0000766
    CSI 2.8
    rCSI 2.59%
    PRS 34.74
  • interstitial cell of Cajal CL0002088
    CSI 2.79
    rCSI 3.55%
    PRS 38.17
  • rod bipolar cell CL0000751
    CSI 2.76
    rCSI 4.97%
    PRS 28.34
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 2.65
    rCSI 13.3%
    PRS 42.96
  • goblet cell CL0000160
    CSI 2.59
    rCSI 2.45%
    PRS 34.68
  • double negative thymocyte CL0002489
    CSI 2.58
    rCSI 1.8%
    PRS 40.34
  • skin fibroblast CL0002620
    CSI 2.54
    rCSI 2.19%
    PRS 43.71
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 2.54
    rCSI 5.78%
    PRS 33.18
  • radial glial cell CL0000681
    CSI 2.52
    rCSI 3.5%
    PRS 33.74
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.52
    rCSI 1.95%
    PRS 33.18
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 2.5
    rCSI 1.8%
    PRS 44.72
  • hematopoietic precursor cell CL0008001
    CSI 2.36
    rCSI 2.43%
    PRS 50.09
  • immature B cell CL0000816
    CSI 2.33
    rCSI 1.73%
    PRS 45.89
  • melanocyte CL0000148
    CSI 2.32
    rCSI 1.72%
    PRS 28.9
  • T follicular helper cell CL0002038
    CSI 2.31
    rCSI 1.73%
    PRS 47.62
  • unswitched memory B cell CL0000970
    CSI 2.3
    rCSI 1.94%
    PRS 49.57
  • ionocyte CL0005006
    CSI 2.3
    rCSI 2.46%
    PRS 31.44
  • epithelial cell of lung CL0000082
    CSI 2.28
    rCSI 1.89%
    PRS 32.05
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.27
    rCSI 1.53%
    PRS 41.76
  • CD4-positive helper T cell CL0000492
    CSI 2.27
    rCSI 1.72%
    PRS 44.41
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 2.26
    rCSI 1.34%
    PRS 46.22
  • early lymphoid progenitor CL0000936
    CSI 2.19
    rCSI 1.92%
    PRS 38.12
  • M cell of gut CL0000682
    CSI 2.19
    rCSI 2.33%
    PRS 49.41
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 2.18
    rCSI 5.21%
    PRS 25.33
  • intestine goblet cell CL0019031
    CSI 2.17
    rCSI 1.93%
    PRS 33.17
  • stem cell CL0000034
    CSI 2.15
    rCSI 2.08%
    PRS 25.88
  • pancreatic D cell CL0000173
    CSI 2.1
    rCSI 2.06%
    PRS 35.72
  • cerebral cortex endothelial cell CL1001602
    CSI 2.1
    rCSI 3.63%
    PRS 26.16
  • precursor B cell CL0000817
    CSI 2.1
    rCSI 1.84%
    PRS 42.71
  • renal alpha-intercalated cell CL0005011
    CSI 2.08
    rCSI 2.79%
    PRS 41.08
  • interneuron CL0000099
    CSI 2.01
    rCSI 4.03%
    PRS 25.47
  • alveolar type 1 fibroblast cell CL4028004
    CSI 1.98
    rCSI 2.16%
    PRS 37.17
  • colon epithelial cell CL0011108
    CSI 1.97
    rCSI 2.07%
    PRS 31.37
  • pro-B cell CL0000826
    CSI 1.91
    rCSI 1.58%
    PRS 34.14
  • hematopoietic stem cell CL0000037
    CSI 1.91
    rCSI 1.27%
    PRS 37.9
  • lymphoid lineage restricted progenitor cell CL0000838
    CSI 1.9
    rCSI 7.39%
    PRS 52.54
  • ON-bipolar cell CL0000749
    CSI 1.9
    rCSI 2.82%
    PRS 36.9
  • bronchus fibroblast of lung CL2000093
    CSI 1.89
    rCSI 1.54%
    PRS 34.49
  • pluripotent stem cell CL0002248
    CSI 1.87
    rCSI 55.95%
    PRS 58.87
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 1.86
    rCSI 2.25%
    PRS 39.97
  • respiratory suprabasal cell CL4033048
    CSI 1.86
    rCSI 2.38%
    PRS 38
  • group 3 innate lymphoid cell CL0001071
    CSI 1.85
    rCSI 1.39%
    PRS 36.1
  • inhibitory interneuron CL0000498
    CSI 1.85
    rCSI 4.26%
    PRS 27.77
  • lung neuroendocrine cell CL1000223
    CSI 1.84
    rCSI 2.72%
    PRS 37.79
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.82
    rCSI 1.64%
    PRS 30.88
  • direct pathway medium spiny neuron CL4023026
    CSI 1.79
    rCSI 42.97%
    PRS 20.72
  • fibroblast of lung CL0002553
    CSI 1.78
    rCSI 1.66%
    PRS 33.37
  • neural crest cell CL0011012
    CSI 1.78
    rCSI 1.4%
    PRS 23.71
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.77
    rCSI 2.11%
    PRS 21.21
  • chondrocyte CL0000138
    CSI 1.76
    rCSI 2.8%
    PRS 28.41
  • forebrain radial glial cell CL0013000
    CSI 1.74
    rCSI 5.59%
    PRS 42.22
  • intestinal epithelial cell CL0002563
    CSI 1.73
    rCSI 1.81%
    PRS 33.87
  • dendritic cell, human CL0001056
    CSI 1.73
    rCSI 2.65%
    PRS 39.37
  • Mueller cell CL0000636
    CSI 1.72
    rCSI 3.93%
    PRS 28.97
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 1.71
    rCSI 3.1%
    PRS 29.19
  • activated CD4-positive, alpha-beta T cell CL0000896
    CSI 1.69
    rCSI 1.56%
    PRS 53.43
  • vascular leptomeningeal cell CL4023051
    CSI 1.69
    rCSI 2.96%
    PRS 27.15
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.68
    rCSI 6.04%
    PRS 20.31
  • enteroendocrine cell CL0000164
    CSI 1.62
    rCSI 2.21%
    PRS 36.24
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.61
    rCSI 2.07%
    PRS 32.08
  • plasmablast CL0000980
    CSI 1.61
    rCSI 1.27%
    PRS 39.29
  • mature B cell CL0000785
    CSI 1.59
    rCSI 1.38%
    PRS 41.47
  • extravillous trophoblast CL0008036
    CSI 1.57
    rCSI 1.95%
    PRS 29.96
  • cytotoxic T cell CL0000910
    CSI 0.1
    rCSI 0.8%
    PRS 45.8%
  • central nervous system neuron CL2000029
    CSI 0.3
    rCSI 2.1%
    PRS 23.7%
  • medium spiny neuron CL1001474
    CSI 0.3
    rCSI 2.8%
    PRS 22.8%
  • paneth cell of colon CL0009009
    CSI 0.4
    rCSI 3.6%
    PRS 62.5%
  • ON parasol ganglion cell CL4033052
    CSI 0.4
    rCSI 5.3%
    PRS 28.2%
  • retinal cone cell CL0000573
    CSI 0.4
    rCSI 0.7%
    PRS 26.2%
  • respiratory basal cell CL0002633
    CSI 0.4
    rCSI 0.5%
    PRS 38.9%
  • epithelial cell of nephron CL1000449
    CSI 0.4
    rCSI 4.2%
    PRS 78.2%
  • pancreatic PP cell CL0002275
    CSI 0.5
    rCSI 1.8%
    PRS 49.6%
  • pancreatic epsilon cell CL0005019
    CSI 0.5
    rCSI 2.5%
    PRS 58.6%
  • pancreatic stellate cell CL0002410
    CSI 0.6
    rCSI 3.2%
    PRS 45.0%
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.6
    rCSI 1.7%
    PRS 36.4%
  • lung secretory cell CL1000272
    CSI 0.6
    rCSI 1.5%
    PRS 31.8%
  • amacrine cell CL0000561
    CSI 0.6
    rCSI 1.8%
    PRS 27.0%
  • transit amplifying cell of small intestine CL0009012
    CSI 0.6
    rCSI 2.7%
    PRS 53.6%
  • podocyte CL0000653
    CSI 0.6
    rCSI 2.7%
    PRS 32.3%
  • glial cell CL0000125
    CSI 0.7
    rCSI 2.5%
    PRS 29.9%
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 0.7
    rCSI 1.2%
    PRS 20.6%
  • erythroid lineage cell CL0000764
    CSI 0.7
    rCSI 4.6%
    PRS 56.7%
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.7
    rCSI 4.3%
    PRS 22.4%
  • primitive red blood cell CL0002355
    CSI 0.7
    rCSI 3.9%
    PRS 48.7%
  • Cajal-Retzius cell CL0000695
    CSI 0.7
    rCSI 5.8%
    PRS 52.9%
  • GABAergic amacrine cell CL4030027
    CSI 0.8
    rCSI 2.6%
    PRS 28.4%
  • large pre-B-II cell CL0000957
    CSI 0.8
    rCSI 2.2%
    PRS 49.0%
  • retinal ganglion cell CL0000740
    CSI 0.8
    rCSI 1.7%
    PRS 24.5%
  • progenitor cell CL0011026
    CSI 0.8
    rCSI 1.7%
    PRS 41.2%
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 0.8
    rCSI 2.2%
    PRS 42.1%
  • type B pancreatic cell CL0000169
    CSI 0.8
    rCSI 1.8%
    PRS 31.1%
  • alveolar adventitial fibroblast CL4028006
    CSI 0.8
    rCSI 1.3%
    PRS 34.2%
  • enteroendocrine cell of small intestine CL0009006
    CSI 0.8
    rCSI 1.8%
    PRS 47.6%
  • myeloid lineage restricted progenitor cell CL0000839
    CSI 0.8
    rCSI 4.3%
    PRS 57.0%
  • retinal bipolar neuron CL0000748
    CSI 0.8
    rCSI 1.6%
    PRS 25.5%
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.9
    rCSI 2.1%
    PRS 20.7%
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.9
    rCSI 2.7%
    PRS 22.3%
  • hematopoietic multipotent progenitor cell CL0000837
    CSI 0.9
    rCSI 2.1%
    PRS 49.8%
  • lung ciliated cell CL1000271
    CSI 0.9
    rCSI 1.0%
    PRS 25.5%
  • duct epithelial cell CL0000068
    CSI 0.9
    rCSI 1.3%
    PRS 35.7%
  • OFF-bipolar cell CL0000750
    CSI 1.0
    rCSI 1.3%
    PRS 44.9%
  • intestinal tuft cell CL0019032
    CSI 1.0
    rCSI 1.5%
    PRS 37.8%
  • retinal blood vessel endothelial cell CL0002585
    CSI 1.0
    rCSI 1.6%
    PRS 36.5%
  • mesenchymal stem cell CL0000134
    CSI 1.0
    rCSI 10.8%
    PRS 50.9%
  • transit amplifying cell of colon CL0009011
    CSI 1.0
    rCSI 1.2%
    PRS 37.2%
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 1.0
    rCSI 2.9%
    PRS 48.8%
  • OFF midget ganglion cell CL4033047
    CSI 1.0
    rCSI 21.2%
    PRS 29.7%
  • choroid plexus epithelial cell CL0000706
    CSI 1.1
    rCSI 1.8%
    PRS 26.4%
  • mesodermal cell CL0000222
    CSI 1.1
    rCSI 1.4%
    PRS 32.3%
  • glioblast CL0000030
    CSI 1.1
    rCSI 1.8%
    PRS 28.8%
  • pancreatic acinar cell CL0002064
    CSI 1.1
    rCSI 1.5%
    PRS 37.1%
  • paneth cell CL0000510
    CSI 1.1
    rCSI 1.7%
    PRS 49.5%
  • retinal rod cell CL0000604
    CSI 1.2
    rCSI 2.1%
    PRS 32.8%
  • basal cell CL0000646
    CSI 1.2
    rCSI 1.6%
    PRS 35.4%
  • intermediate monocyte CL0002393
    CSI 1.2
    rCSI 1.8%
    PRS 34.7%
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.2
    rCSI 1.5%
    PRS 20.1%
  • acinar cell CL0000622
    CSI 1.2
    rCSI 1.8%
    PRS 43.1%
  • common dendritic progenitor CL0001029
    CSI 1.3
    rCSI 1.6%
    PRS 42.1%
  • T-helper 17 cell CL0000899
    CSI 1.3
    rCSI 1.0%
    PRS 54.3%
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 1.3
    rCSI 1.8%
    PRS 31.4%
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.3
    rCSI 31.1%
    PRS 21.5%
  • fraction A pre-pro B cell CL0002045
    CSI 1.3
    rCSI 1.5%
    PRS 56.8%
  • cerebellar granule cell CL0001031
    CSI 1.3
    rCSI 1.9%
    PRS 31.2%
  • GABAergic neuron CL0000617
    CSI 1.3
    rCSI 4.5%
    PRS 25.2%
  • effector memory CD4-positive, alpha-beta T cell CL0000905
    CSI 1.3
    rCSI 1.8%
    PRS 62.2%
  • keratinocyte CL0000312
    CSI 1.3
    rCSI 1.1%
    PRS 38.4%
  • pancreatic ductal cell CL0002079
    CSI 1.4
    rCSI 2.6%
    PRS 34.9%
  • granulocyte monocyte progenitor cell CL0000557
    CSI 1.4
    rCSI 1.2%
    PRS 37.0%
  • common myeloid progenitor CL0000049
    CSI 1.4
    rCSI 1.1%
    PRS 33.8%
  • ciliated epithelial cell CL0000067
    CSI 1.4
    rCSI 1.3%
    PRS 24.9%
  • conjunctival epithelial cell CL1000432
    CSI 1.5
    rCSI 2.2%
    PRS 33.9%
  • peripheral nervous system neuron CL2000032
    CSI 1.5
    rCSI 2.0%
    PRS 28.9%
  • ependymal cell CL0000065
    CSI 1.5
    rCSI 3.0%
    PRS 20.0%
  • respiratory hillock cell CL4030023
    CSI 1.5
    rCSI 2.7%
    PRS 49.5%
  • glycinergic amacrine cell CL4030028
    CSI 1.5
    rCSI 3.9%
    PRS 33.9%
  • transit amplifying cell CL0009010
    CSI 1.5
    rCSI 2.3%
    PRS 49.7%
  • hepatic stellate cell CL0000632
    CSI 1.5
    rCSI 5.7%
    PRS 28.6%
  • pancreatic A cell CL0000171
    CSI 1.5
    rCSI 1.6%
    PRS 35.5%
  • ON midget ganglion cell CL4033046
    CSI 1.5
    rCSI 31.4%
    PRS 28.6%
  • glutamatergic neuron CL0000679
    CSI 1.6
    rCSI 3.2%
    PRS 31.0%
  • extravillous trophoblast CL0008036
    CSI 1.6
    rCSI 2.0%
    PRS 30.0%
  • mature B cell CL0000785
    CSI 1.6
    rCSI 1.4%
    PRS 41.5%
  • plasmablast CL0000980
    CSI 1.6
    rCSI 1.3%
    PRS 39.3%
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.6
    rCSI 2.1%
    PRS 32.1%
  • enteroendocrine cell CL0000164
    CSI 1.6
    rCSI 2.2%
    PRS 36.2%
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.7
    rCSI 6.0%
    PRS 20.3%
  • vascular leptomeningeal cell CL4023051
    CSI 1.7
    rCSI 3.0%
    PRS 27.2%
  • activated CD4-positive, alpha-beta T cell CL0000896
    CSI 1.7
    rCSI 1.6%
    PRS 53.4%
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 1.7
    rCSI 3.1%
    PRS 29.2%
  • Mueller cell CL0000636
    CSI 1.7
    rCSI 3.9%
    PRS 29.0%
  • dendritic cell, human CL0001056
    CSI 1.7
    rCSI 2.7%
    PRS 39.4%
  • intestinal epithelial cell CL0002563
    CSI 1.7
    rCSI 1.8%
    PRS 33.9%
  • forebrain radial glial cell CL0013000
    CSI 1.7
    rCSI 5.6%
    PRS 42.2%
  • chondrocyte CL0000138
    CSI 1.8
    rCSI 2.8%
    PRS 28.4%
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.8
    rCSI 2.1%
    PRS 21.2%
  • neural crest cell CL0011012
    CSI 1.8
    rCSI 1.4%
    PRS 23.7%
  • fibroblast of lung CL0002553
    CSI 1.8
    rCSI 1.7%
    PRS 33.4%
  • direct pathway medium spiny neuron CL4023026
    CSI 1.8
    rCSI 43.0%
    PRS 20.7%
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.8
    rCSI 1.6%
    PRS 30.9%
  • lung neuroendocrine cell CL1000223
    CSI 1.8
    rCSI 2.7%
    PRS 37.8%
  • inhibitory interneuron CL0000498
    CSI 1.9
    rCSI 4.3%
    PRS 27.8%
  • group 3 innate lymphoid cell CL0001071
    CSI 1.9
    rCSI 1.4%
    PRS 36.1%
  • respiratory suprabasal cell CL4033048
    CSI 1.9
    rCSI 2.4%
    PRS 38.0%

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 [NAE1](/details-gene/8883) (NEDD8 Activating Enzyme E1 Subunit 1) is a protein-coding gene located on chromosome 16q22.1. It encodes a crucial component of the neddylation pathway, a post-translational modification system analogous to ubiquitination. Specifically, [NAE1](/details-gene/8883) forms a heterodimer that functions as the E1 activating enzyme for the ubiquitin-like protein NEDD8 ([Link](https://doi.org/10.1074/jbc.274.17.12036)). This process is fundamental for the activity of cullin-RING E3 ubiquitin ligases, which regulate the turnover of proteins involved in critical cellular processes, including cell cycle control and signal transduction. **Overall**, expression data reveals that [NAE1](/details-gene/8883) is highly significant in a diverse range of metabolically active and functionally specialized cells, including immune cells like the [plasmacytoid dendritic cell, human](/details-cell/CL0001058), various neuronal subtypes such as the [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011), and secretory cells like the [mucus secreting cell](/details-cell/CL0000319). Historically, it was also identified as APP-BP1, a protein that binds to the amyloid precursor protein (APP), implicating it in neuronal apoptosis and the pathophysiology of Alzheimer's disease ([Link](https://doi.org/10.1074/jbc.271.19.11339), [Link](https://doi.org/10.1083/jcb.200304003)). ## Cellular Roles and Expression Landscape The expression profile of [NAE1](/details-gene/8883) highlights its foundational role in cells with high rates of protein turnover, proliferation, or complex signaling. Its high significance (CSI: 14.97) in the [plasmacytoid dendritic cell, human](/details-cell/CL0001058), a key producer of type I interferons, suggests that neddylation is a critical regulatory checkpoint in innate antiviral immunity. A prominent feature of the [NAE1](/details-gene/8883) expression landscape is its high significance across multiple neuronal and glial cell types. It is a key marker in several GABAergic cortical interneurons, including [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011) and [chandelier pvalb GABAergic cortical interneuron](/details-cell/CL4023036), as well as in progenitor cells like the [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338) and support cells like [Bergmann glial cell](/details-cell/CL0000644) and [Schwann cell](/details-cell/CL0002573). This widespread importance in the nervous system is consistent with its documented role in regulating neuronal apoptosis and its interaction with APP ([Link](https://doi.org/10.1074/jbc.275.12.8929)). Beyond the immune and nervous systems, [NAE1](/details-gene/8883) shows high significance in various epithelial and muscle cells that require robust protein regulation for their specialized functions. These include [mucus secreting cell](/details-cell/CL0000319), [multi-ciliated epithelial cell](/details-cell/CL0005012), and [tracheobronchial smooth muscle cell](/details-cell/CL0019019). The gene's activity in T cells, specifically the [mature alpha-beta T cell](/details-cell/CL0000791), further underscores its importance in adaptive immunity, likely by controlling the cell cycle progression and degradation of signaling molecules during T cell activation. ## Pathways and Molecular Function Functionally, [NAE1](/details-gene/8883) is central to the [Neddylation](/details-reactome/R-HSA-8951664) pathway. It exhibits [Nedd8 activating enzyme activity](/details-go/GO0019781), the first and rate-limiting step in conjugating NEDD8 to target proteins. This activity is essential for the function of cullin-RING ligases (CRLs), the largest family of E3 ubiquitin ligases, which target a vast number of substrates for proteasomal degradation. Through its role in [protein neddylation](/details-go/GO0045116), [NAE1](/details-gene/8883) is deeply involved in processes that rely on precise protein degradation, such as [mitotic dna replication checkpoint signaling](/details-go/GO0033314) and the general [regulation of apoptotic process](/details-go/GO0042981). Its specific connection to neuronal biology is highlighted by its annotation in [neuron apoptotic process](/details-go/GO0051402) and [regulation of postsynapse assembly](/details-go/GO0150052), consistent with its high expression in neurons and its documented binding to APP. The enzyme's localization to the [cytoplasm](/details-go/GO0005737), [cytosol](/details-go/GO0005829), and [nucleus](/details-go/GO0005634) reflects the broad distribution of its substrates and the ubiquitous nature of the neddylation pathway. ## Research Directions The widespread and critical role of [NAE1](/details-gene/8883) in protein homeostasis presents numerous avenues for future research, particularly at the intersection of immunology, neurobiology, and cancer. **Proposed Hypotheses:** 1. Given its top significance in [plasmacytoid dendritic cell, human](/details-cell/CL0001058), it is hypothesized that [NAE1](/details-gene/8883)-mediated neddylation is indispensable for the massive production of type I interferons in these cells, potentially by regulating the stability and activity of key transcription factors in the Toll-like receptor signaling pathway, such as IRF7. 2. Based on its high expression in multiple cortical interneuron subtypes and its established link to APP, we hypothesize that localized dysregulation of [NAE1](/details-gene/8883) activity at the synapse contributes to the synaptic dysfunction and excitotoxicity observed in early-stage Alzheimer's disease, preceding overt neuronal apoptosis. **Experimental Approach:** To test the first hypothesis regarding the role of [NAE1](/details-gene/8883) in pDC function, a conditional knockout mouse model could be generated where *Nae1* is specifically deleted in pDCs (e.g., using a *Siglech*-Cre driver line). Bone marrow-derived or splenic pDCs from these knockout and control mice would be isolated and stimulated *in vitro* with TLR9 agonists (e.g., CpG-A). The production of IFN-alpha and other cytokines would be quantified by ELISA and qPCR. Furthermore, RNA-sequencing could be performed on stimulated pDCs to identify global transcriptomic changes and pinpoint downstream pathways affected by the loss of neddylation. A significant reduction in interferon production would validate the crucial role of [NAE1](/details-gene/8883) in pDC antiviral responses. **Therapeutic Potential:** [NAE1](/details-gene/8883) is a well-established therapeutic target, primarily in oncology. As the rate-limiting enzyme in neddylation, its **inhibition** blocks the activity of cullin-RING E3 ligases, leading to the accumulation of CRL substrates that induce cell cycle arrest and apoptosis. The small molecule inhibitor Pevonedistat (MLN4924), which targets the NAE1 complex, has been investigated in numerous clinical trials for hematological malignancies and solid tumors. Given its essential role in all proliferating cells, the main challenge for [NAE1](/details-gene/8883)-targeted therapies is managing on-target toxicities in healthy tissues. Future therapeutic strategies may focus on developing more selective inhibitors or employing targeted delivery systems to concentrate the therapeutic agent in diseased cells, such as cancer cells or pathologically activated immune cells.

Genular Protein ID: 2570762664

Symbol: ULA1_HUMAN

Name: NEDD8-activating enzyme E1 regulatory subunit

UniProtKB Accession Codes:

Database IDs:

Citations:

PubMed ID: 8626687

Title: APP-BP1, a novel protein that binds to the carboxyl-terminal region of the amyloid precursor protein.

PubMed ID: 8626687

DOI: 10.1074/jbc.271.19.11339

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 10493829

Title: Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q.

PubMed ID: 10493829

DOI: 10.1006/geno.1999.5927

PubMed ID: 11230166

Title: Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.

PubMed ID: 11230166

DOI: 10.1101/gr.gr1547r

PubMed ID: 15616553

Title: The sequence and analysis of duplication-rich human chromosome 16.

PubMed ID: 15616553

DOI: 10.1038/nature03187

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: 10207026

Title: Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway.

PubMed ID: 10207026

DOI: 10.1074/jbc.274.17.12036

PubMed ID: 10722740

Title: The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in neurons.

PubMed ID: 10722740

DOI: 10.1074/jbc.275.12.8929

PubMed ID: 12740388

Title: Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer.

PubMed ID: 12740388

DOI: 10.1074/jbc.m303177200

PubMed ID: 14557245

Title: APP-BP1 mediates APP-induced apoptosis and DNA synthesis and is increased in Alzheimer's disease brain.

PubMed ID: 14557245

DOI: 10.1083/jcb.200304003

PubMed ID: 12694406

Title: ASPP2 inhibits APP-BP1-mediated NEDD8 conjugation to cullin-1 and decreases APP-BP1-induced cell proliferation and neuronal apoptosis.

PubMed ID: 12694406

DOI: 10.1046/j.1471-4159.2003.01727.x

PubMed ID: 18627766

Title: TRIP12 functions as an E3 ubiquitin ligase of APP-BP1.

PubMed ID: 18627766

DOI: 10.1016/j.bbrc.2008.07.019

PubMed ID: 19608861

Title: Lysine acetylation targets protein complexes and co-regulates major cellular functions.

PubMed ID: 19608861

DOI: 10.1126/science.1175371

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

PubMed ID: 36608681

Title: Bi-allelic variants in NAE1 cause intellectual disability, ischiopubic hypoplasia, stress-mediated lymphopenia and neurodegeneration.

PubMed ID: 36608681

DOI: 10.1016/j.ajhg.2022.12.003

PubMed ID: 14690597

Title: The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1.

PubMed ID: 14690597

DOI: 10.1016/s1097-2765(03)00452-0

PubMed ID: 12646924

Title: Insights into the ubiquitin transfer cascade from the structure of the activating enzyme for NEDD8.

PubMed ID: 12646924

DOI: 10.1038/nature01456

PubMed ID: 15361859

Title: A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8.

PubMed ID: 15361859

DOI: 10.1038/nsmb826

Sequence Information:

  • Length: 534
  • Mass: 60246
  • Checksum: 5EC8D3ACE6374F21
  • Sequence:
  • MAQLGKLLKE QKYDRQLRLW GDHGQEALES AHVCLINATA TGTEILKNLV LPGIGSFTII 
    DGNQVSGEDA GNNFFLQRSS IGKNRAEAAM EFLQELNSDV SGSFVEESPE NLLDNDPSFF 
    CRFTVVVATQ LPESTSLRLA DVLWNSQIPL LICRTYGLVG YMRIIIKEHP VIESHPDNAL 
    EDLRLDKPFP ELREHFQSYD LDHMEKKDHS HTPWIVIIAK YLAQWYSETN GRIPKTYKEK 
    EDFRDLIRQG ILKNENGAPE DEENFEEAIK NVNTALNTTQ IPSSIEDIFN DDRCINITKQ 
    TPSFWILARA LKEFVAKEGQ GNLPVRGTIP DMIADSGKYI KLQNVYREKA KKDAAAVGNH 
    VAKLLQSIGQ APESISEKEL KLLCSNSAFL RVVRCRSLAE EYGLDTINKD EIISSMDNPD 
    NEIVLYLMLR AVDRFHKQQG RYPGVSNYQV EEDIGKLKSC LTGFLQEYGL SVMVKDDYVH 
    EFCRYGAAEP HTIAAFLGGA AAQEVIKIIT KQFVIFNNTY IYSGMSQTSA TFQL