-
Notifications
You must be signed in to change notification settings - Fork 63
/
Copy pathconcentricData.json
9752 lines (9539 loc) · 339 KB
/
concentricData.json
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
518
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
538
539
540
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
571
572
573
574
575
576
577
578
579
580
581
582
583
584
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
603
604
605
606
607
608
609
610
611
612
613
614
615
616
617
618
619
620
621
622
623
624
625
626
627
628
629
630
631
632
633
634
635
636
637
638
639
640
641
642
643
644
645
646
647
648
649
650
651
652
653
654
655
656
657
658
659
660
661
662
663
664
665
666
667
668
669
670
671
672
673
674
675
676
677
678
679
680
681
682
683
684
685
686
687
688
689
690
691
692
693
694
695
696
697
698
699
700
701
702
703
704
705
706
707
708
709
710
711
712
713
714
715
716
717
718
719
720
721
722
723
724
725
726
727
728
729
730
731
732
733
734
735
736
737
738
739
740
741
742
743
744
745
746
747
748
749
750
751
752
753
754
755
756
757
758
759
760
761
762
763
764
765
766
767
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
821
822
823
824
825
826
827
828
829
830
831
832
833
834
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
865
866
867
868
869
870
871
872
873
874
875
876
877
878
879
880
881
882
883
884
885
886
887
888
889
890
891
892
893
894
895
896
897
898
899
900
901
902
903
904
905
906
907
908
909
910
911
912
913
914
915
916
917
918
919
920
921
922
923
924
925
926
927
928
929
930
931
932
933
934
935
936
937
938
939
940
941
942
943
944
945
946
947
948
949
950
951
952
953
954
955
956
957
958
959
960
961
962
963
964
965
966
967
968
969
970
971
972
973
974
975
976
977
978
979
980
981
982
983
984
985
986
987
988
989
990
991
992
993
994
995
996
997
998
999
1000
{
"nodes":[
{
"data":{
"id":"HIRA",
"altered":0,
"rank":148,
"cited":53,
"uniprotdesc":"Cooperates with ASF1A to promote replication-independentchromatin assembly. Required for the periodic repression ofhistone gene transcription during the cell cycle. Required for theformation of senescence-associated heterochromatin foci (SAHF) andefficient senescence-associated cell cycle exit.",
"isseed":false,
"uniprot":"P54198",
"isvalid":true,
"importance":3
},
"position":{
"x":539.5,
"y":641.7372431003224
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"SERPINE1",
"altered":0,
"rank":5,
"cited":7063,
"uniprotdesc":"Serine protease inhibitor. This inhibitor acts as 'bait'for tissue plasminogen activator, urokinase, protein C andmatriptase-3/TMPRSS7. Its rapid interaction with PLAT may functionas a major control point in the regulation of fibrinolysis.",
"isseed":false,
"uniprot":"P05121",
"isvalid":true,
"importance":3
},
"position":{
"x":670.4301869950953,
"y":229.70989985711336
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"FAS",
"altered":0,
"rank":38,
"cited":1011,
"uniprotdesc":"Receptor for TNFSF6/FASLG. The adapter molecule FADDrecruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolyticactivation which initiates the subsequent cascade of caspases(aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheraltolerance, in the antigen-stimulated suicide of mature T-cells, orboth. The secreted isoforms 2 to 6 block apoptosis (in vitro).",
"isseed":false,
"uniprot":"P25445",
"isvalid":true,
"importance":3
},
"position":{
"x":771.3915110914829,
"y":613.8066148172879
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"H1F0",
"altered":0,
"rank":179,
"cited":8,
"uniprotdesc":"Histones H1 are necessary for the condensation ofnucleosome chains into higher-order structures. The H1F0 histonesare found in cells that are in terminal stages of differentiationor that have low rates of cell division.",
"isseed":false,
"uniprot":"P07305",
"isvalid":true,
"importance":3
},
"position":{
"x":396.564243092928,
"y":545.1295331255458
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"CHEK2",
"altered":0,
"rank":42,
"cited":859,
"uniprotdesc":"Serine/threonine-protein kinase which is required forcheckpoint-mediated cell cycle arrest, activation of DNA repairand apoptosis in response to the presence of DNA double-strandbreaks. May also negatively regulate cell cycle progression duringunperturbed cell cycles. Following activation, phosphorylatesnumerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest throughphosphorylation of CDC25A, CDC25B and CDC25C, inhibiting theiractivity. Inhibition of CDC25 phosphatase activity leads toincreased inhibitory tyrosine phosphorylation of CDK-cyclincomplexes and blocks cell cycle progression. May alsophosphorylate NEK6 which is involved in G2/M cell cycle arrest.Regulates DNA repair through phosphorylation of BRCA2, enhancingthe association of RAD51 with chromatin which promotes DNA repairby homologous recombination. Also stimulates the transcription ofgenes involved in DNA repair (including BRCA2) through thephosphorylation and activation of the transcription factor FOXM1.Regulates apoptosis through the phosphorylation of p53/TP53, MDM4and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 mayalleviate inhibition by MDM2, leading to accumulation of activep53/TP53. Phosphorylation of MDM4 may also reduce degradation ofp53/TP53. Also controls the transcription of pro-apoptotic genesthrough phosphorylation of the transcription factor E2F1. Tumorsuppressor, it may also have a DNA damage-independent function inmitotic spindle assembly by phosphorylating BRCA1. Its absence maybe a cause of the chromosomal instability observed in some cancercells. ",
"isseed":false,
"uniprot":"O96017",
"isvalid":true,
"importance":3
},
"position":{
"x":665.61605725324,
"y":327.88536532731405
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"COL18A1",
"altered":0,
"rank":157,
"cited":30,
"uniprotdesc":"COLA18A probably plays a major role in determining theretinal structure as well as in the closure of the neural tube.Endostatin potently inhibits endothelial cellproliferation and angiogenesis. May inhibit angiogenesis bybinding to the heparan sulfate proteoglycans involved in growthfactor signaling.",
"isseed":false,
"uniprot":"P39060",
"isvalid":true,
"importance":3
},
"position":{
"x":315.495548442639,
"y":356.3503242429216
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"CREBBP",
"altered":0,
"rank":24,
"cited":2442,
"uniprotdesc":"Acetylates histones, giving a specific tag fortranscriptional activation. Also acetylates non-histone proteins,like NCOA3 and FOXO1. Binds specifically to phosphorylated CREBand enhances its transcriptional activity toward cAMP-responsivegenes. Acts as a coactivator of ALX1 in the presence of EP300.Acts as a circadian transcriptional coactivator which enhances theactivity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers.",
"isseed":false,
"uniprot":"Q92793",
"isvalid":true,
"importance":3
},
"position":{
"x":468.2392322240752,
"y":311.08612174318614
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"FDXR",
"altered":0,
"rank":147,
"cited":54,
"uniprotdesc":"Serves as the first electron transfer protein in all themitochondrial P450 systems. Including cholesterol side chaincleavage in all steroidogenic tissues, steroid 11-betahydroxylation in the adrenal cortex, 25-OH-vitamin D3-24hydroxylation in the kidney, and sterol C-27 hydroxylation in theliver.",
"isseed":false,
"uniprot":"P22570",
"isvalid":true,
"importance":3
},
"position":{
"x":614.0116881932149,
"y":209.57981996234878
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"SMYD2",
"altered":0,
"rank":175,
"cited":12,
"uniprotdesc":"Protein-lysine N-methyltransferase that methylates bothhistones and non-histone proteins, including p53/TP53 and RB1.Specifically methylates histone H3 'Lys-4' (H3K4me) anddimethylates histone H3 'Lys-36' (H3K36me2). Shows even highermethyltransferase activity on p53/TP53. Monomethylates 'Lys-370'of p53/TP53, leading to decreased DNA-binding activity andsubsequent transcriptional regulation activity of p53/TP53.Monomethylates RB1 at 'Lys-860'. ",
"isseed":false,
"uniprot":"Q9NRG4",
"isvalid":true,
"importance":3
},
"position":{
"x":799.3458853307084,
"y":560.8271840491047
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"ATR",
"altered":0,
"rank":52,
"cited":628,
"uniprotdesc":"Serine/threonine protein kinase which activatescheckpoint signaling upon genotoxic stresses such as ionizingradiation (IR), ultraviolet light (UV), or DNA replicationstalling, thereby acting as a DNA damage sensor. Recognizes thesubstrate consensus sequence [ST]-Q. Phosphorylates BRCA1, CHEK1,MCM2, RAD17, RPA2, SMC1 and p53/TP53, which collectively inhibitDNA replication and mitosis and promote DNA repair, recombinationand apoptosis. Phosphorylates 'Ser-139' of histone variantH2AX/H2AFX at sites of DNA damage, thereby regulating DNA damageresponse mechanism. Required for FANCD2 ubiquitination. Criticalfor maintenance of fragile site stability and efficient regulationof centrosome duplication. ",
"isseed":false,
"uniprot":"Q13535",
"isvalid":true,
"importance":3
},
"position":{
"x":696.7065384003552,
"y":570.6754072575451
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"HGF",
"altered":0,
"rank":4,
"cited":7554,
"uniprotdesc":"Potent mitogen for mature parenchymal hepatocyte cells,seems to be a hepatotrophic factor, and acts as a growth factorfor a broad spectrum of tissues and cell types. Activating ligandfor the receptor tyrosine kinase MET by binding to it andpromoting its dimerization. ",
"isseed":false,
"uniprot":"P14210",
"isvalid":true,
"importance":3
},
"position":{
"x":732.163947642761,
"y":659.0776363377252
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"ATM",
"altered":0,
"rank":25,
"cited":2298,
"uniprotdesc":"Serine/threonine protein kinase which activatescheckpoint signaling upon double strand breaks (DSBs), apoptosisand genotoxic stresses such as ionizing ultraviolet A light (UVA),thereby acting as a DNA damage sensor. Recognizes the substrateconsensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histonevariant H2AX/H2AFX at double strand breaks (DSBs), therebyregulating DNA damage response mechanism. Also plays a role inpre-B cell allelic exclusion, a process leading to expression of asingle immunoglobulin heavy chain allele to enforce clonality andmonospecific recognition by the B-cell antigen receptor (BCR)expressed on individual B-lymphocytes. After the introduction ofDNA breaks by the RAG complex on one immunoglobulin allele, actsby mediating a repositioning of the second allele topericentromeric heterochromatin, preventing accessibility to theRAG complex and recombination of the second allele. Also involvedin signal transduction and cell cycle control. May function as atumor suppressor. Necessary for activation of ABL1 and SAPK.Phosphorylates DYRK2, CHEK2, p53/TP53, FANCD2, NFKBIA, BRCA1,CTIP, nibrin (NBN), TERF1, RAD9 and DCLRE1C. May play a role invesicle and/or protein transport. Could play a role in T-celldevelopment, gonad and neurological function. Plays a role inreplication-dependent histone mRNA degradation. Binds DNA ends.Phosphorylation of DYRK2 in nucleus in response to genotoxicstress prevents its MDM2-mediated ubiquitination and subsequentproteasome degradation. Phosphorylates ATF2 which stimulates itsfunction in DNA damage response. ",
"isseed":false,
"uniprot":"Q13315",
"isvalid":true,
"importance":3
},
"position":{
"x":723.6214512404813,
"y":517.2928623066505
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"TP63",
"altered":0,
"rank":37,
"cited":1171,
"uniprotdesc":"Acts as a sequence specific DNA binding transcriptionalactivator or repressor. The isoforms contain a varying set oftransactivation and auto-regulating transactivation inhibitingdomains thus showing an isoform specific activity. Isoform 2activates RIPK4 transcription. May be required in conjunction withTP73/p73 for initiation of p53/TP53 dependent apoptosis inresponse to genotoxic insults and the presence of activatedoncogenes. Involved in Notch signaling by probably inducing JAG1and JAG2. Plays a role in the regulation of epithelialmorphogenesis. The ratio of DeltaN-type and TA*-type isoforms maygovern the maintenance of epithelial stem cell compartments andregulate the initiation of epithelial stratification from theundifferentiated embryonal ectoderm. Required for limb formationfrom the apical ectodermal ridge. Activates transcription of thep21 promoter. ",
"isseed":false,
"uniprot":"Q9H3D4",
"isvalid":true,
"importance":3
},
"position":{
"x":554.5,
"y":495.5
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"GPX1",
"altered":0,
"rank":13,
"cited":3644,
"uniprotdesc":"Protects the hemoglobin in erythrocytes from oxidativebreakdown.",
"isseed":false,
"uniprot":"P07203",
"isvalid":true,
"importance":3
},
"position":{
"x":412.4474306913114,
"y":244.4618875964815
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"TRIAP1",
"altered":0,
"rank":183,
"cited":7,
"uniprotdesc":"Involved in the modulation of the mitochondrialapoptotic pathway by ensuring the accumulation of cardiolipin (CL)in mitochondrial membranes. In vitro, the TRIAP1:PRELID1 complexmediates the transfer of phosphatidic acid (PA) between liposomesand probably functions as a PA transporter across themitochondrion intermembrane space to provide PA for CL synthesisin the inner membrane. Mediates cell survival by inhibitingactivation of caspase-9 which prevents induction of apoptosis.",
"isseed":false,
"uniprot":"O43715",
"isvalid":true,
"importance":3
},
"position":{
"x":554.5,
"y":202.751489857487
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"HIST1H1E",
"altered":0,
"rank":167,
"cited":19,
"uniprotdesc":"Histone H1 protein binds to linker DNA betweennucleosomes forming the macromolecular structure known as thechromatin fiber. Histones H1 are necessary for the condensation ofnucleosome chains into higher-order structured fibers. Acts alsoas a regulator of individual gene transcription through chromatinremodeling, nucleosome spacing and DNA methylation (Bysimilarity). ",
"isseed":false,
"uniprot":"P10412",
"isvalid":true,
"importance":3
},
"position":{
"x":509.931522689569,
"y":636.667218490667
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"HIST1H1D",
"altered":0,
"rank":184,
"cited":6,
"uniprotdesc":"Histone H1 protein binds to linker DNA betweennucleosomes forming the macromolecular structure known as thechromatin fiber. Histones H1 are necessary for the condensation ofnucleosome chains into higher-order structured fibers. Acts alsoas a regulator of individual gene transcription through chromatinremodeling, nucleosome spacing and DNA methylation (Bysimilarity). ",
"isseed":false,
"uniprot":"P16402",
"isvalid":true,
"importance":3
},
"position":{
"x":385.3785487595187,
"y":517.2928623066505
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"HIST1H1C",
"altered":0,
"rank":174,
"cited":13,
"uniprotdesc":"Histone H1 protein binds to linker DNA betweennucleosomes forming the macromolecular structure known as thechromatin fiber. Histones H1 are necessary for the condensation ofnucleosome chains into higher-order structured fibers. Acts alsoas a regulator of individual gene transcription through chromatinremodeling, nucleosome spacing and DNA methylation (Bysimilarity). ",
"isseed":false,
"uniprot":"P16403",
"isvalid":true,
"importance":3
},
"position":{
"x":379.058170659647,
"y":487.9662051382201
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"HIST1H1B",
"altered":0,
"rank":96,
"cited":209,
"uniprotdesc":"Histone H1 protein binds to linker DNA betweennucleosomes forming the macromolecular structure known as thechromatin fiber. Histones H1 are necessary for the condensation ofnucleosome chains into higher-order structured fibers. Acts alsoas a regulator of individual gene transcription through chromatinremodeling, nucleosome spacing and DNA methylation (Bysimilarity). ",
"isseed":false,
"uniprot":"P16401",
"isvalid":true,
"importance":3
},
"position":{
"x":381.59546915616875,
"y":428.2362230943135
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"HIST1H1A",
"altered":0,
"rank":173,
"cited":13,
"uniprotdesc":"Histone H1 protein binds to linker DNA betweennucleosomes forming the macromolecular structure known as thechromatin fiber. Histones H1 are necessary for the condensation ofnucleosome chains into higher-order structured fibers. Acts alsoas a regulator of individual gene transcription through chromatinremodeling, nucleosome spacing and DNA methylation (Bysimilarity). ",
"isseed":false,
"uniprot":"Q02539",
"isvalid":true,
"importance":3
},
"position":{
"x":443.3839427467599,
"y":327.88536532731405
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"TP53",
"altered":0,
"rank":0,
"cited":24824,
"uniprotdesc":"Acts as a tumor suppressor in many tumor types; inducesgrowth arrest or apoptosis depending on the physiologicalcircumstances and cell type. Involved in cell cycle regulation asa trans-activator that acts to negatively regulate cell divisionby controlling a set of genes required for this process. One ofthe activated genes is an inhibitor of cyclin-dependent kinases.Apoptosis induction seems to be mediated either by stimulation ofBAX and FAS antigen expression, or by repression of Bcl-2expression. In cooperation with mitochondrial PPIF is involved inactivating oxidative stress-induced necrosis; the function islargely independent of transcription. Induces the transcription oflong intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptionalrepression leading to apoptosis and seem to have to effect oncell-cycle regulation. Implicated in Notch signaling cross-over.Prevents CDK7 kinase activity when associated to CAK complex inresponse to DNA damage, thus stopping cell cycle progression.Isoform 2 enhances the transactivation activity of isoform 1 fromsome but not all TP53-inducible promoters. Isoform 4 suppressestransactivation activity and impairs growth suppression mediatedby isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis.",
"isseed":true,
"uniprot":"P04637",
"isvalid":true,
"importance":4
},
"position":{
"x":554.5,
"y":465.5
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"GADD45A",
"altered":0,
"rank":98,
"cited":198,
"uniprotdesc":"In T-cells, functions as a regulator of p38 MAPKs byinhibiting p88 phosphorylation and activity (By similarity). Mightaffect PCNA interaction with some CDK (cell division proteinkinase) complexes; stimulates DNA excision repair in vitro andinhibits entry of cells into S phase. ",
"isseed":false,
"uniprot":"P24522",
"isvalid":true,
"importance":3
},
"position":{
"x":554.5,
"y":375.5
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"PML",
"altered":0,
"rank":35,
"cited":1300,
"uniprotdesc":"Functions via its association with PML-nuclear bodies(PML-NBs) in a wide range of important cellular processes,including tumor suppression, transcriptional regulation,apoptosis, senescence, DNA damage response, and viral defensemechanisms. Acts as the scaffold of PML-NBs allowing otherproteins to shuttle in and out, a process which is regulated bySUMO-mediated modifications and interactions. Isoform PML-4 has amultifaceted role in the regulation of apoptosis and growthsuppression: activates RB1 and inhibits AKT1 via interactions withPP1 and PP2A phosphatases respectively, negatively affects thePI3K pathway by inhibiting MTOR and activating PTEN, andpositively regulates p53/TP53 by acting at different levels (bypromoting its acetylation and phosphorylation and by inhibitingits MDM2-dependent degradation). Isoform PML-4 also: acts as atranscriptional repressor of TBX2 during cellular senescence andthe repression is dependent on a functional RBL2/E2F4 repressorcomplex, regulates double-strand break repair in gamma-irradiation-induced DNA damage responses via its interaction withWRN, acts as a negative regulator of telomerase by interactingwith TERT, and regulates PER2 nuclear localization and circadianfunction. Isoform PML-6 inhibits specifically the activity of thetetrameric form of PKM. The nuclear isoforms (isoform PML-1,isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5) inconcert with SATB1 are involved in local chromatin-loop remodelingand gene expression regulation at the MHC-I locus. Isoform PML-2is required for efficient IFN-gamma induced MHC II genetranscription via regulation of CIITA. Cytoplasmic PML is involvedin the regulation of the TGF-beta signaling pathway. PML alsoregulates transcription activity of ELF4 and can act as animportant mediator for TNF-alpha- and IFN-alpha-mediatedinhibition of endothelial cell network formation and migration.Exhibits antiviral activity against both DNA and RNAviruses. The antiviral activity can involve one or severalisoform(s) and can be enhanced by the permanent PML-NB-associatedprotein DAXX or by the recruitment of p53/TP53 within thesestructures. Isoform PML-4 restricts varicella zoster virus (VZV)via sequestration of virion capsids in PML-NBs thereby preventingtheir nuclear egress and inhibiting formation of infectious virusparticles. The sumoylated isoform PML-4 restricts rabies virus byinhibiting viral mRNA and protein synthesis. The cytoplasmicisoform PML-14 can restrict herpes simplex virus-1 (HHV-1)replication by sequestering the viral E3 ubiquitin-protein ligaseICP0 in the cytoplasm. Isoform PML-6 shows restriction activitytowards human cytomegalovirus (HCMV) and influenza A virus strainsPR8(H1N1) and ST364(H3N2). Sumoylated isoform PML-4 and isoformPML-12 show antiviral activity against encephalomyocarditis virus(EMCV) by promoting nuclear sequestration of viral polymerase(P3D-POL) within PML NBs. Isoform PML-3 exhibits antiviralactivity against poliovirus by inducing apoptosis in infectedcells through the recruitment and the activation of p53/TP53 inthe PML-NBs. Isoform PML-3 represses human foamy virus (HFV)transcription by complexing the HFV transactivator, bel1/tas,preventing its binding to viral DNA. PML may positively regulateinfectious hepatitis C viral (HCV) production and isoform PML-2may enhance adenovirus transcription.",
"isseed":false,
"uniprot":"P29590",
"isvalid":true,
"importance":3
},
"position":{
"x":554.5,
"y":555.5
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"SUMO1",
"altered":0,
"rank":36,
"cited":1235,
"uniprotdesc":"Ubiquitin-like protein that can be covalently attachedto proteins as a monomer or a lysine-linked polymer. Covalentattachment via an isopeptide bond to its substrates requires prioractivation by the E1 complex SAE1-SAE2 and linkage to the E2enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4,RANBP2 or CBX4. This post-translational modification on lysineresidues of proteins plays a crucial role in a number of cellularprocesses such as nuclear transport, DNA replication and repair,mitosis and signal transduction. Involved for instance intargeting RANGAP1 to the nuclear pore complex protein RANBP2.Polymeric SUMO1 chains are also susceptible to polyubiquitinationwhich functions as a signal for proteasomal degradation ofmodified proteins. May also regulate a network of genes involvedin palate development. ",
"isseed":false,
"uniprot":"P63165",
"isvalid":true,
"importance":3
},
"position":{
"x":554.5,
"y":288.62556472004735
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"PPP2CA",
"altered":0,
"rank":146,
"cited":55,
"uniprotdesc":"PP2A is the major phosphatase for microtubule-associatedproteins (MAPs). PP2A can modulate the activity of phosphorylase Bkinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2kinase. Cooperates with SGOL2 to protect centromeric cohesin fromseparase-mediated cleavage in oocytes specifically during meiosisI (By similarity). Can dephosphorylate SV40 large T antigen andp53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259'.",
"isseed":false,
"uniprot":"P67775",
"isvalid":true,
"importance":3
},
"position":{
"x":727.4045308438311,
"y":428.2362230943131
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"PPP2CB",
"altered":0,
"rank":185,
"cited":6,
"uniprotdesc":"PP2A can modulate the activity of phosphorylase B kinasecasein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase.",
"isseed":false,
"uniprot":"P62714",
"isvalid":true,
"importance":3
},
"position":{
"x":584.3919246562758,
"y":291.16974245431265
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"PRKAA1",
"altered":0,
"rank":78,
"cited":330,
"uniprotdesc":"Catalytic subunit of AMP-activated protein kinase(AMPK), an energy sensor protein kinase that plays a key role inregulating cellular energy metabolism. In response to reduction ofintracellular ATP levels, AMPK activates energy-producing pathwaysand inhibits energy-consuming processes: inhibits protein,carbohydrate and lipid biosynthesis, as well as cell growth andproliferation. AMPK acts via direct phosphorylation of metabolicenzymes, and by longer-term effects via phosphorylation oftranscription regulators. Also acts as a regulator of cellularpolarity by remodeling the actin cytoskeleton; probably byindirectly activating myosin. Regulates lipid synthesis byphosphorylating and inactivating lipid metabolic enzymes such asACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid andcholesterol synthesis by phosphorylating acetyl-CoA carboxylase(ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes,respectively. Regulates insulin-signaling and glycolysis byphosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucoseuptake in muscle by increasing the translocation of the glucosetransporter SLC2A4/GLUT4 to the plasma membrane, possibly bymediating phosphorylation of TBC1D4/AS160. Regulates transcriptionand chromatin structure by phosphorylating transcriptionregulators involved in energy metabolism such as CRTC2/TORC2,FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A,p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator ofglucose homeostasis in liver by phosphorylating CRTC2/TORC2,leading to CRTC2/TORC2 sequestration in the cytoplasm. In responseto stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph),leading to promote transcription. Acts as a key regulator of cellgrowth and proliferation by phosphorylating TSC2, RPTOR andATG1/ULK1: in response to nutrient limitation, negativelyregulates the mTORC1 complex by phosphorylating RPTOR component ofthe mTORC1 complex and by phosphorylating and activating TSC2. Inresponse to nutrient limitation, promotes autophagy byphosphorylating and activating ATG1/ULK1. AMPK also acts as aregulator of circadian rhythm by mediating phosphorylation ofCRY1, leading to destabilize it. May regulate the Wnt signalingpathway by phosphorylating CTNNB1, leading to stabilize it. Alsohas tau-protein kinase activity: in response to amyloid beta A4protein (APP) exposure, activated by CAMKK2, leading tophosphorylation of MAPT/TAU; however the relevance of such dataremains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1,NOS3 and SLC12A1. ",
"isseed":false,
"uniprot":"Q13131",
"isvalid":true,
"importance":3
},
"position":{
"x":731.2150654362375,
"y":457.9932361520795
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"PRKAA2",
"altered":0,
"rank":29,
"cited":2074,
"uniprotdesc":"Catalytic subunit of AMP-activated protein kinase(AMPK), an energy sensor protein kinase that plays a key role inregulating cellular energy metabolism. In response to reduction ofintracellular ATP levels, AMPK activates energy-producing pathwaysand inhibits energy-consuming processes: inhibits protein,carbohydrate and lipid biosynthesis, as well as cell growth andproliferation. AMPK acts via direct phosphorylation of metabolicenzymes, and by longer-term effects via phosphorylation oftranscription regulators. Also acts as a regulator of cellularpolarity by remodeling the actin cytoskeleton; probably byindirectly activating myosin. Regulates lipid synthesis byphosphorylating and inactivating lipid metabolic enzymes such asACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid andcholesterol synthesis by phosphorylating acetyl-CoA carboxylase(ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes,respectively. Regulates insulin-signaling and glycolysis byphosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucoseuptake in muscle by increasing the translocation of the glucosetransporter SLC2A4/GLUT4 to the plasma membrane, possibly bymediating phosphorylation of TBC1D4/AS160. Regulates transcriptionand chromatin structure by phosphorylating transcriptionregulators involved in energy metabolism such as CRTC2/TORC2,FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A,p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator ofglucose homeostasis in liver by phosphorylating CRTC2/TORC2,leading to CRTC2/TORC2 sequestration in the cytoplasm. In responseto stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph),leading to promote transcription. Acts as a key regulator of cellgrowth and proliferation by phosphorylating TSC2, RPTOR andATG1/ULK1: in response to nutrient limitation, negativelyregulates the mTORC1 complex by phosphorylating RPTOR component ofthe mTORC1 complex and by phosphorylating and activating TSC2. Inresponse to nutrient limitation, promotes autophagy byphosphorylating and activating ATG1/ULK1. AMPK also acts as aregulator of circadian rhythm by mediating phosphorylation ofCRY1, leading to destabilize it. May regulate the Wnt signalingpathway by phosphorylating CTNNB1, leading to stabilize it. Alsophosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.",
"isseed":false,
"uniprot":"P54646",
"isvalid":true,
"importance":3
},
"position":{
"x":613.4239130642807,
"y":298.7290842958664
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"MAPK11",
"altered":0,
"rank":127,
"cited":81,
"uniprotdesc":"Serine/threonine kinase which acts as an essentialcomponent of the MAP kinase signal transduction pathway. MAPK11 isone of the four p38 MAPKs which play an important role in thecascades of cellular responses evoked by extracellular stimulisuch as proinflammatory cytokines or physical stress leading todirect activation of transcription factors. Accordingly, p38 MAPKsphosphorylate a broad range of proteins and it has been estimatedthat they may have approximately 200 to 300 substrates each.MAPK11 functions are mostly redundant with those of MAPK14. Someof the targets are downstream kinases which are activated throughphosphorylation and further phosphorylate additional targets.RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate andactivate transcription factors such as CREB1, ATF1, the NF-kappa-Bisoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylatehistone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 andRPS6KA4/MSK2 play important roles in the rapid induction ofimmediate-early genes in response to stress or mitogenic stimuli,either by inducing chromatin remodeling or by recruiting thetranscription machinery. On the other hand, two other kinasetargets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the controlof gene expression mostly at the post-transcriptional level, byphosphorylating ZFP36 (tristetraprolin) and ELAVL1, and byregulating EEF2K, which is important for the elongation of mRNAduring translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinasesactivated by p38 MAPKs, regulate protein synthesis byphosphorylating the initiation factor EIF4E2. In the cytoplasm,the p38 MAPK pathway is an important regulator of proteinturnover. For example, CFLAR is an inhibitor of TNF-inducedapoptosis whose proteasome-mediated degradation is regulated byp38 MAPK phosphorylation. Ectodomain shedding of transmembraneproteins is regulated by p38 MAPKs as well. In response toinflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation isrequired for ADAM17-mediated ectodomain shedding of TGF-alphafamily ligands, which results in the activation of EGFR signalingand cell proliferation. Additional examples of p38 MAPK substratesare the FGFR1. FGFR1 can be translocated from the extracellularspace into the cytosol and nucleus of target cells, and regulatesprocesses such as rRNA synthesis and cell growth. FGFR1translocation requires p38 MAPK activation. In the nucleus, manytranscription factors are phosphorylated and activated by p38MAPKs in response to different stimuli. Classical examples includeATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C andMEF2A. The p38 MAPKs are emerging as important modulators of geneexpression by regulating chromatin modifiers and remodelers. Thepromoters of several genes involved in the inflammatory response,such as IL6, IL8 and IL12B, display a p38 MAPK-dependentenrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) inLPS-stimulated myeloid cells. This phosphorylation enhances theaccessibility of the cryptic NF-kappa-B-binding sites markingpromoters for increased NF-kappa-B recruitment.",
"isseed":false,
"uniprot":"Q15759",
"isvalid":true,
"importance":3
},
"position":{
"x":640.7607677759248,
"y":311.0861217431862
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"TP73",
"altered":0,
"rank":116,
"cited":124,
"uniprotdesc":"Participates in the apoptotic response to DNA damage.Isoforms containing the transactivation domain are pro-apoptotic,isoforms lacking the domain are anti-apoptotic and block thefunction of p53 and transactivating p73 isoforms. May be a tumorsuppressor protein. ",
"isseed":false,
"uniprot":"O15350",
"isvalid":true,
"importance":3
},
"position":{
"x":554.5,
"y":435.5
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"CCNB1",
"altered":0,
"rank":62,
"cited":491,
"uniprotdesc":"Essential for the control of the cell cycle at the G2/M(mitosis) transition. ",
"isseed":false,
"uniprot":"P14635",
"isvalid":true,
"importance":3
},
"position":{
"x":455.45477593090067,
"y":612.0421763339963
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"MAPK12",
"altered":0,
"rank":131,
"cited":79,
"uniprotdesc":"Serine/threonine kinase which acts as an essentialcomponent of the MAP kinase signal transduction pathway. MAPK12 isone of the four p38 MAPKs which play an important role in thecascades of cellular responses evoked by extracellular stimulisuch as proinflammatory cytokines or physical stress leading todirect activation of transcription factors such as ELK1 and ATF2.Accordingly, p38 MAPKs phosphorylate a broad range of proteins andit has been estimated that they may have approximately 200 to 300substrates each. Some of the targets are downstream kinases suchas MAPKAPK2, which are activated through phosphorylation andfurther phosphorylate additional targets. Plays a role in myoblastdifferentiation and also in the down-regulation of cyclin D1 inresponse to hypoxia in adrenal cells suggesting MAPK12 may inhibitcell proliferation while promoting differentiation. PhosphorylatesDLG1. Following osmotic shock, MAPK12 in the cell nucleusincreases its association with nuclear DLG1, thereby causingdissociation of DLG1-SFPQ complexes. This function is independentof its catalytic activity and could affect mRNA processing and/orgene transcription to aid cell adaptation to osmolarity changes inthe environment. Regulates UV-induced checkpoint signaling andrepair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1expression and basal glucose uptake in L6 myotubes; and negativelyregulates SLC2A4 expression and contraction-mediated glucoseuptake in adult skeletal muscle. C-Jun (JUN) phosphorylation isstimulated by MAPK14 and inhibited by MAPK12, leading to adistinct AP-1 regulation. MAPK12 is required for the normalkinetochore localization of PLK1, prevents chromosomal instabilityand supports mitotic cell viability. MAPK12-signaling is alsopositively regulating the expansion of transient amplifyingmyogenic precursor cells during muscle growth and regeneration.",
"isseed":false,
"uniprot":"P53778",
"isvalid":true,
"importance":3
},
"position":{
"x":569.5000000000001,
"y":641.7372431003224
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"MAPK13",
"altered":0,
"rank":126,
"cited":88,
"uniprotdesc":"Serine/threonine kinase which acts as an essentialcomponent of the MAP kinase signal transduction pathway. MAPK13 isone of the four p38 MAPKs which play an important role in thecascades of cellular responses evoked by extracellular stimulisuch as proinflammatory cytokines or physical stress leading todirect activation of transcription factors such as ELK1 and ATF2.Accordingly, p38 MAPKs phosphorylate a broad range of proteins andit has been estimated that they may have approximately 200 to 300substrates each. MAPK13 is one of the less studied p38 MAPKisoforms. Some of the targets are downstream kinases such asMAPKAPK2, which are activated through phosphorylation and furtherphosphorylate additional targets. Plays a role in the regulationof protein translation by phosphorylating and inactivating EEF2K.Involved in cytoskeletal remodeling through phosphorylation ofMAPT and STMN1. Mediates UV irradiation induced up-regulation ofthe gene expression of CXCL14. Plays an important role in theregulation of epidermal keratinocyte differentiation, apoptosisand skin tumor development. Phosphorylates the transcriptionalactivator MYB in response to stress which leads to rapid MYBdegradation via a proteasome-dependent pathway. MAPK13 alsophosphorylates and down-regulates PRKD1 during regulation ofinsulin secretion in pancreatic beta cells.",
"isseed":false,
"uniprot":"O15264",
"isvalid":true,
"importance":3
},
"position":{
"x":687.2747400718758,
"y":348.6435313966404
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"MAPK14",
"altered":0,
"rank":23,
"cited":2528,
"uniprotdesc":"Serine/threonine kinase which acts as an essentialcomponent of the MAP kinase signal transduction pathway. MAPK14 isone of the four p38 MAPKs which play an important role in thecascades of cellular responses evoked by extracellular stimulisuch as proinflammatory cytokines or physical stress leading todirect activation of transcription factors. Accordingly, p38 MAPKsphosphorylate a broad range of proteins and it has been estimatedthat they may have approximately 200 to 300 substrates each. Someof the targets are downstream kinases which are activated throughphosphorylation and further phosphorylate additional targets.RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate andactivate transcription factors such as CREB1, ATF1, the NF-kappa-Bisoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylatehistone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 andRPS6KA4/MSK2 play important roles in the rapid induction ofimmediate-early genes in response to stress or mitogenic stimuli,either by inducing chromatin remodeling or by recruiting thetranscription machinery. On the other hand, two other kinasetargets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the controlof gene expression mostly at the post-transcriptional level, byphosphorylating ZFP36 (tristetraprolin) and ELAVL1, and byregulating EEF2K, which is important for the elongation of mRNAduring translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinasesactivated by p38 MAPKs, regulate protein synthesis byphosphorylating the initiation factor EIF4E2. MAPK14 interactsalso with casein kinase II, leading to its activation throughautophosphorylation and further phosphorylation of TP53/p53. Inthe cytoplasm, the p38 MAPK pathway is an important regulator ofprotein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation isregulated by p38 MAPK phosphorylation. In a similar way, MAPK14phosphorylates the ubiquitin ligase SIAH2, regulating its activitytowards EGLN3. MAPK14 may also inhibit the lysosomal degradationpathway of autophagy by interfering with the intracellulartrafficking of the transmembrane protein ATG9. Another function ofMAPK14 is to regulate the endocytosis of membrane receptors bydifferent mechanisms that impinge on the small GTPase RAB5A. Inaddition, clathrin-mediated EGFR internalization induced byinflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5Aeffectors. Ectodomain shedding of transmembrane proteins isregulated by p38 MAPKs as well. In response to inflammatorystimuli, p38 MAPKs phosphorylate the membrane-associatedmetalloprotease ADAM17. Such phosphorylation is required forADAM17-mediated ectodomain shedding of TGF-alpha family ligands,which results in the activation of EGFR signaling and cellproliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can betranslocated from the extracellular space into the cytosol andnucleus of target cells, and regulates processes such as rRNAsynthesis and cell growth. FGFR1 translocation requires p38 MAPKactivation. In the nucleus, many transcription factors arephosphorylated and activated by p38 MAPKs in response to differentstimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH,DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging asimportant modulators of gene expression by regulating chromatinmodifiers and remodelers. The promoters of several genes involvedin the inflammatory response, such as IL6, IL8 and IL12B, displaya p38 MAPK-dependent enrichment of histone H3 phosphorylation on'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. Thisphosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-Brecruitment. Phosphorylates CDC25B and CDC25C which is requiredfor binding to 14-3-3 proteins and leads to initiation of a G2delay after ultraviolet radiation. Phosphorylates TIAR followingDNA damage, releasing TIAR from GADD45A mRNA and preventing mRNAdegradation. The p38 MAPKs may also have kinase-independent roles,which are thought to be due to the binding to targets in theabsence of phosphorylation. Protein O-Glc-N-acylation catalyzed bythe OGT is regulated by MAPK14, and, although OGT does not seem tobe phosphorylated by MAPK14, their interaction increases uponMAPK14 activation induced by glucose deprivation. This interactionmay regulate OGT activity by recruiting it to specific targetssuch as neurofilament H, stimulating its O-Glc-N-acylation.Required in mid-fetal development for the growth of embryo-derivedblood vessels in the labyrinth layer of the placenta. Also playsan essential role in developmental and stress-inducederythropoiesis, through regulation of EPO gene expression. IsoformMXI2 activation is stimulated by mitogens and oxidative stress andonly poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play arole in the early onset of apoptosis. Phosphorylates S100A9 at'Thr-113'. ",
"isseed":false,
"uniprot":"Q16539",
"isvalid":true,
"importance":3
},
"position":{
"x":705.1137353610045,
"y":372.7634453076487
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"PRKAB2",
"altered":0,
"rank":189,
"cited":4,
"uniprotdesc":"Non-catalytic subunit of AMP-activated protein kinase(AMPK), an energy sensor protein kinase that plays a key role inregulating cellular energy metabolism. In response to reduction ofintracellular ATP levels, AMPK activates energy-producing pathwaysand inhibits energy-consuming processes: inhibits protein,carbohydrate and lipid biosynthesis, as well as cell growth andproliferation. AMPK acts via direct phosphorylation of metabolicenzymes, and by longer-term effects via phosphorylation oftranscription regulators. Also acts as a regulator of cellularpolarity by remodeling the actin cytoskeleton; probably byindirectly activating myosin. Beta non-catalytic subunit acts as ascaffold on which the AMPK complex assembles, via its C-terminusthat bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1,PRKAG2 or PRKAG3).",
"isseed":false,
"uniprot":"O43741",
"isvalid":true,
"importance":3
},
"position":{
"x":718.6198477055347,
"y":399.5512210521357
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"PRKAB1",
"altered":0,
"rank":73,
"cited":368,
"uniprotdesc":"Non-catalytic subunit of AMP-activated protein kinase(AMPK), an energy sensor protein kinase that plays a key role inregulating cellular energy metabolism. In response to reduction ofintracellular ATP levels, AMPK activates energy-producing pathwaysand inhibits energy-consuming processes: inhibits protein,carbohydrate and lipid biosynthesis, as well as cell growth andproliferation. AMPK acts via direct phosphorylation of metabolicenzymes, and by longer-term effects via phosphorylation oftranscription regulators. Also acts as a regulator of cellularpolarity by remodeling the actin cytoskeleton; probably byindirectly activating myosin. Beta non-catalytic subunit acts as ascaffold on which the AMPK complex assembles, via its C-terminusthat bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1,PRKAG2 or PRKAG3).",
"isseed":false,
"uniprot":"Q9Y478",
"isvalid":true,
"importance":3
},
"position":{
"x":476.5577136594006,
"y":420.49999999999994
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"EP300",
"altered":0,
"rank":19,
"cited":2835,
"uniprotdesc":"Functions as histone acetyltransferase and regulatestranscription via chromatin remodeling. Acetylates all four corehistones in nucleosomes. Histone acetylation gives an epigenetictag for transcriptional activation. Mediates cAMP-gene regulationby binding specifically to phosphorylated CREB protein. Mediatesacetylation of histone H3 at 'Lys-122' (H3K122ac), a modificationthat localizes at the surface of the histone octamer andstimulates transcription, possibly by promoting nucleosomeinstability. Mediates acetylation of histone H3 at 'Lys-27'(H3K27ac). Also functions as acetyltransferase for nonhistonetargets. Acetylates 'Lys-131' of ALX1 and acts as its coactivatorin the presence of CREBBP. Acetylates SIRT2 and is proposed toindirectly increase the transcriptional activity of TP53 throughacetylation and subsequent attenuation of SIRT2 deacetylasefunction. Acetylates HDAC1 leading to its inactivation andmodulation of transcription. Acts as a TFAP2A-mediatedtranscriptional coactivator in presence of CITED2. Plays a role asa coactivator of NEUROD1-dependent transcription of the secretinand p21 genes and controls terminal differentiation of cells inthe intestinal epithelium. Promotes cardiac myocyte enlargement.Can also mediate transcriptional repression. Binds to and may beinvolved in the transforming capacity of the adenovirus E1Aprotein. In case of HIV-1 infection, it is recruited by the viralprotein Tat. Regulates Tat's transactivating activity and may helpinducing chromatin remodeling of proviral genes. Acetylates FOXO1and enhances its transcriptional activity. Acetylates BCL6 wichdisrupts its ability to recruit histone deacetylases and hindersits transcriptional repressor activity. Participates in CLOCK orNPAS2-regulated rhythmic gene transcription; exhibits a circadianassociation with CLOCK or NPAS2, correlating with increase inPER1/2 mRNA and histone H3 acetylation on the PER1/2 promoter.Acetylates MTA1 at 'Lys-626' which is essential for itstranscriptional coactivator activity (PubMed:10733570,PubMed:11430825, PubMed:11701890, PubMed:12402037,PubMed:12586840, PubMed:12929931, PubMed:14645221,PubMed:15186775, PubMed:15890677, PubMed:16617102,PubMed:16762839, PubMed:18722353, PubMed:18995842,PubMed:23415232, PubMed:23911289, PubMed:23934153,PubMed:8945521). Acetylates XBP1 isoform 2; acetylation increasesprotein stability of XBP1 isoform 2 and enhances itstranscriptional activity (By similarity).",
"isseed":false,
"uniprot":"Q09472",
"isvalid":true,
"importance":3
},
"position":{
"x":476.5577136594005,
"y":510.5
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"IGBP1",
"altered":0,
"rank":125,
"cited":89,
"uniprotdesc":"Associated to surface IgM-receptor; may be involved insignal transduction. Involved in regulation of the catalyticactivity of the phosphatases PP2A, PP4 and PP6 by protecting theirpartially folded catalytic subunits from degradativepolyubiquitination until they associate with regulatory subunits.",
"isseed":false,
"uniprot":"P78318",
"isvalid":true,
"importance":3
},
"position":{
"x":729.941829340353,
"y":487.96620513822
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"FBXO11",
"altered":0,
"rank":188,
"cited":5,
"uniprotdesc":"Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediatesthe ubiquitination and subsequent proteasomal degradation oftarget proteins, such as DTL/CDT2, BCL6 and PRDM1/BLIMP1. TheSCF(FBXO11) complex mediates ubiquitination and degradation ofBCL6, thereby playing a role in the germinal center B-cellsterminal differentiation toward memory B-cells and plasma cells.The SCF(FBXO11) complex also mediates ubiquitination anddegradation of DTL, an important step for the regulation of TGF-beta signaling, cell migration and the timing of the cell-cycleprogression and exit. Binds to and neddylates phosphorylatedp53/TP53, inhibiting its transcriptional activity. SCF(FBXO11)does not seem to direct ubiquitination of p53/TP53.",
"isseed":false,
"uniprot":"Q86XK2",
"isvalid":true,
"importance":3
},
"position":{
"x":481.64519932573637,
"y":626.6730246484053
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"HMGB1",
"altered":0,
"rank":54,
"cited":617,
"uniprotdesc":"DNA binding proteins that associates with chromatin andhas the ability to bend DNA. Binds preferentially single-strandedDNA. Involved in V(D)J recombination by acting as a cofactor ofthe RAG complex. Acts by stimulating cleavage and RAG proteinbinding at the 23 bp spacer of conserved recombination signalsequences (RSS). Heparin-binding protein that has a role in theextension of neurite-type cytoplasmic processes in developingcells (By similarity). ",
"isseed":false,
"uniprot":"P09429",
"isvalid":true,
"importance":3
},
"position":{
"x":712.435756907072,
"y":545.1295331255459
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"NEDD8",
"altered":0,
"rank":205,
"cited":236,
"uniprotdesc":"Ubiquitin-like protein which plays an important role incell cycle control and embryogenesis. Covalent attachment to itssubstrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M. Attachment of NEDD8 tocullins activates their associated E3 ubiquitin ligase activity,and thus promotes polyubiquitination and proteasomal degradationof cyclins and other regulatory proteins.",
"isseed":false,
"uniprot":"Q15843",
"isvalid":true,
"importance":2
},
"position":{
"x":432.1137033013474,
"y":593.195576415127
},
"group":"nodes",
"removed":false,
"selected":false,
"selectable":true,
"locked":false,
"grabbable":true,
"classes":""
},
{
"data":{
"id":"ASF1A",
"altered":0,
"rank":161,
"cited":27,
"uniprotdesc":"Histone chaperone that facilitates histone depositionand histone exchange and removal during nucleosome assembly anddisassembly. Cooperates with chromatin assembly factor 1 (CAF-1)to promote replication-dependent chromatin assembly and with HIRAto promote replication-independent chromatin assembly. Requiredfor the formation of senescence-associated heterochromatin foci(SAHF) and efficient senescence-associated cell cycle exit.",
"isseed":false,
"uniprot":"Q9Y294",
"isvalid":true,
"importance":3
},
"position":{
"x":412.29346159964496,