IdA
string
IdB
string
labels
int64
mechanism
string
effect
string
score
float64
sentence
string
signor_id
string
O14757
Q92934
1
phosphorylation
down-regulates activity
0.2
Chkl binds and phosphorylates BAD protein.|Taken together, our results suggest that Chk1 may inactivate BAD by associating with and phosphorylating residues critical for BAD function in response to DNA damage.
SIGNOR-279159
P17252
Q92686
1
phosphorylation
up-regulates activity
0.394
Phosphorylation of RC3 by PKC alpha, beta, or gamma was stimulated by Ca2+, phospholipid, and diacylglycerol. A single site, Ser36, which is adjacent to the predicted calmodulin (CaM)-binding domain, was phosphorylated by these enzymes. Phosphorylation of RC3 by PKC or PKM, a protease-degraded PKC, was inhibited by CaM. The effect of CaM apparently targets at RC3, as phosphorylation of protamine sulfate by PKM was not inhibited by CaM.
SIGNOR-248913
P10636
O60285
0
phosphorylation
up-regulates quantity
0.249
These results confirm that the effect of Nuak1 over tau levels is mainly due to tau phosphorylation at Ser356 by Nuak1.|Western blot analysis revealed that a 50% reduction in Nuak1 was sufficient to decrease tau levels in the brain (XREF_FIG).
SIGNOR-279306
Q96J02
P46531
1
ubiquitination
down-regulates
0.644
Itch binds to the n-terminal portion of the notch intracellular domain via its ww domains and promotes ubiquitination of notch through its hect ubiquitin ligase domain.
SIGNOR-80702
Q9P0U3
P31749
1
desumoylation
down-regulates quantity by destabilization
0.28
Although multiple sites on Akt could be SUMOylated, K276 was identified as a major SUMO acceptor site. K276R or E278A mutation reduced SUMOylation of Akt but had little effect on its ubiquitination. Strikingly, these mutations also completely abolished Akt kinase activity. In support of these results, we found that expression of PIAS1 and SUMO1 increased Akt activity, whereas expression of SENP1 reduced Akt1 activity.
SIGNOR-252736
P23443
O60346
0
dephosphorylation
down-regulates activity
0.572
Here we report the identification of ribosomal protein S6 kinase 1 (S6K1) as a novel substrate of PHLPP.
SIGNOR-237454
P05129
P48058
1
phosphorylation
up-regulates
0.702
We found that pka phosphorylation of the ampa receptor subunits glur4 and glur1 directly controlled the synaptic incorporation of ampa receptors in organotypic slices from rat hippocampus.
SIGNOR-97558
Q15796
Q9Y5K5
0
deubiquitination
up-regulates
0.378
Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases
SIGNOR-138876
Q99704
Q13882
0
phosphorylation
down-regulates activity
0.494
BRK downregulates Dok1 via proteasomal degradation.|BRK phosphorylates Dok1 at tyrosine 362.
SIGNOR-278301
Q96PY5
P17252
0
phosphorylation
up-regulates activity
0.2
PKCα associates with and phosphorylates FMNL2 at S1072 within its Diaphanous autoregulatory region, leading to the release of formin autoinhibition.
SIGNOR-273796
P68400
Q08945
1
phosphorylation
down-regulates activity
0.703
CK2 phosphorylates SSRP1 and inhibits its DNA-binding activity. | we identified serines 510, 657, and 688 as phosphorylation targets of CK2 in vitro. Mutagenesis of the three serines revealed that serine 510 was more important for the regulation of SSRP1 DNA-binding activity.
SIGNOR-250961
P18669
Q13153
0
phosphorylation
down-regulates
0.2
Activated pak1 inhibits glycolysis by association of its catalytic domain with pgam-b and subsequent phosphorylation of the enzyme on serine residues 23 and 118, thereby abolishing pgam activity.
SIGNOR-91594
P30305
Q14680
0
phosphorylation
down-regulates activity
0.533
In the present study we show that the human pEg3 kinase is able to specifically phosphorylate CDC25B in vitro. One phosphorylation site was identified and corresponded to serine 323[Ä] Taken together these results suggest that pEg3 is a potential regulator of the G2/M progression and may act antagonistically to the CDC25B phosphatase
SIGNOR-255655
Q6UXI9
Q5H8C1
0
transcriptional regulation
up-regulates quantity by expression
0.366
The loss of QBRICK significantly diminished the expression of nephronectin, an integrin α8β1 ligand necessary for renal development. In vivo, nephronectin associated with QBRICK and localized at the sublamina densa region, where QBRICK was also located. Collectively, these findings indicate that QBRICK facilitates the integrin α8β1-dependent interactions of cells with basement membranes by regulating the basement membrane assembly of nephronectin and explain why renal defects occur in Fraser syndrome.
SIGNOR-253308
P11717
Q7Z6M1
0
relocalization
up-regulates activity
0.385
P40 is a very potent transport factor in that the pure, recombinant protein can stimulate, significantly, an in vitro transport assay that measures transport of mannose 6-phosphate receptors from endosomes to the trans-Golgi network. The functional importance of p40 is confirmed by the finding that anti-p40 antibodies inhibit in vitro transport. Finally, p40 shows synergy with Rab9 in terms of its ability to stimulate mannose 6-phosphate receptor transport. These data are consistent with a model in which p40 and Rab9 act together to drive the process of transport vesicle docking.
SIGNOR-253090
Q8NBP7
P36956
0
transcriptional regulation
up-regulates quantity by expression
0.427
Expression of nuclear forms of sterol-regulatory element binding protein-1 (SREBP-1) and SREBP-2 dramatically increased the promoter activity of PCSK9.
SIGNOR-255222
P05112
O95644
0
transcriptional regulation
up-regulates quantity by expression
0.549
Recombinant NFAT1 can mediate transcription of the interleukin-2, interleukin-4, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor promoters in T cells, suggesting that NFAT1 contributes to the CsA-sensitive transcription of these genes during the immune response.
SIGNOR-254498
Q6ZMU5
P35568
1
ubiquitination
down-regulates quantity by destabilization
0.477
Here, we demonstrate that MG53 induces IRS-1 ubiquitination with the help of the E2 enzyme UBE2H during skeletal myogenesis by examining MG53 disrupted skeletal muscle cells and tissues.|The IRS-1 protein level was decreased by MG53 in a concentration dependent manner and was restored by the addition of MG132, a proteasome inhibitor (XREF_FIG; XREF_SUPPLEMENTARY).
SIGNOR-278520
Q00987
P11309
0
phosphorylation
up-regulates
0.388
Additionally, the pim kinases phosphorylate mdm2 in vitro and in cultured cells at ser166 and ser186, two previously identified targets of other signaling pathways, including akt.
SIGNOR-178619
Q02156
Q8WV44
0
polyubiquitination
down-regulates quantity by destabilization
0.2
RINCK induces the ubiquitination of PKC both in vitro and in cells. Overexpression of RINCK reduces the levels of PKC in cells, whereas genetic knockdown of endogenous RINCK increases the levels of PKC. The RINCK-mediated ubiquitination is likely to be polyubiquitination, because the ubiquitinated PKCβII was detected as a high molecular weight smear.
SIGNOR-271668
P37231
P25874
1
transcriptional regulation
up-regulates quantity by expression
0.533
NFIA binds to and activates the brown-fat-specific enhancers even before differentiation and later facilitates the binding of PPARgamma|NFIA has at least three functions on the transcriptional regulation of brown fat [2]. First, NFIA activates adipogenesis per se, through activating the transcription of Pparg, which encodes PPARgamma. Second, NFIA also activates the brown-fat-specific gene expression (such as Ucp1 and Ppargc1a) independent of the degree of adipocyte differentiation, through facilitating the binding of PPARgamma to the brown-fat-specific enhancers. Third, NFIA represses myogenesis through suppression of myogenic transcription factors such as Myod1 as well as Myog,
SIGNOR-263985
Q15796
P24941
0
phosphorylation
down-regulates activity
0.488
Moreover, CDK2 is the predominant CDK that phosphorylates Smad2 on T8 in myeloma cells, leading to inhibition of Smad2-Smad4 association that precludes transcriptional regulation by Smad2.|Moreover, CDK2 is the predominant cyclin-dependent kinase that phosphorylates Smad2 on T8 in myeloma cells, leading to inhibition of Smad2-Smad4 association that precludes transcriptional regulation by Smad2.
SIGNOR-279678
Q86YT6
P34925
1
ubiquitination
down-regulates
0.327
We discovered that ryk both physically and functionally interacts with the e3 ubiquitin ligase mind bomb 1 (mib1).We Found that overexpressed ryk and mib1 colocalized and that the overexpression of mib1 leads to the loss of surface ryk expression. In addition, biochemical studies revealed that mib1 promotes the ubiquitination and degradation of ryk. Endogenous ryk and mib1 were required for the wnt-dependent activation of wnt/ctnnb1 signaling
SIGNOR-176282
P49841
O43623
1
phosphorylation
down-regulates activity
0.423
GSK3beta controls epithelial-mesenchymal transition and tumor metastasis by CHIP mediated degradation of Slug.|Phosphorylation of Slug by GSK3beta promotes CHIP binding and ubiquitin mediated proteolysis.
SIGNOR-279414
O00141
P10636
1
phosphorylation
down-regulates
0.331
Second, sgk1 indirectly depolymerized mts through the phosphorylation of tau at ser214
SIGNOR-161288
Q14232
P20042
1
guanine nucleotide exchange factor
up-regulates activity
0.78
EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.
SIGNOR-269129
O75955
P12931
0
phosphorylation
up-regulates activity
0.335
Taken together, we conclude that mitochondrial c-Src phosphorylates flotillin-1 at Tyr56 and Tyr149, and that these phosphorylations are required for its interaction with CxII and the prevention of ROS production.
SIGNOR-273805
Q16584
Q02750
1
phosphorylation
up-regulates activity
0.335
Here we report that MLK3 can phosphorylate and activate MEK-1 directly in vitro and also can induce MEK phosphorylation on its activation sites in vivo in COS-7 cells.
SIGNOR-280019
P53350
P13693
1
phosphorylation
down-regulates
0.716
Plk phosphorylates tctp on two serine residues. These results suggest that phosphorylation decreases the microtubule-stabilizing activity of tctp and promotes the increase in microtubule dynamics that occurs after metaphase
SIGNOR-91348
Q5H8C1
Q6UXI9
1
transcriptional regulation
up-regulates quantity by expression
0.366
The loss of QBRICK significantly diminished the expression of nephronectin, an integrin α8β1 ligand necessary for renal development. In vivo, nephronectin associated with QBRICK and localized at the sublamina densa region, where QBRICK was also located. Collectively, these findings indicate that QBRICK facilitates the integrin α8β1-dependent interactions of cells with basement membranes by regulating the basement membrane assembly of nephronectin and explain why renal defects occur in Fraser syndrome.
SIGNOR-253308
P24752
Q9P0J1
1
acetylation
down-regulates activity
0.34
We previously reported that the mitochondrial fraction of FLT3 activates acetyl-CoA acetyltransferase ACAT1 in mitochondria via Y407 phosphorylation to acetylate and inhibit mitochondrial pyruvate dehydrogenase A (PDHA) and PDH phosphatase 1 (PDP1)
SIGNOR-267635
Q9UKT4
P53350
0
phosphorylation
down-regulates
0.783
We propose that the balance of evi5 and polo-like kinase activities determines the timely accumulation of emi1 and cyclin, ensuring mitotic fidelity.
SIGNOR-142949
Q02952
P06493
0
phosphorylation
up-regulates activity
0.322
Mass spectrometry, molecular, and cellular approaches show that CDK1/Cyclin B1 phosphorylates Gravin on threonine 766 to prime the recruitment of the polo-like kinase Plk1 at defined phases of mitosis.
SIGNOR-271839
O00141
Q13164
0
phosphorylation
up-regulates
0.388
Bmk1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinasebmk1 activates sgk by phosphorylation at serine 78.
SIGNOR-105728
P28482
P10636
1
phosphorylation
down-regulates activity
0.566
Using nanoelectrospray mass spectrometry, we have undertaken an extensive comparison of phosphorylation in vitro by several candidate tau kinases, namely, JNK, p38, ERK2, and glycogen synthase kinase 3beta (GSK3beta). Between 10 and 15 sites were identified for each kinase. The three MAP kinases phosphorylated Ser202 and Thr205 but not detectably Ser199, whereas conversely GSK3beta phosphorylated Ser199 but not detectably Ser202 or Thr205. Phosphorylated Ser404 was found with all of these kinases except JNK. The MAP kinases may not be strictly proline specific: p38 phosphorylated the nonproline sites Ser185, Thr245, Ser305, and Ser356, whereas ERK2 was the most strict. All of the sites detected except Thr245 and Ser305 are known or suspected phosphorylation sites in paired helical filament-tau extracted from Alzheimer brains. Thus, the three MAP kinases and GSK3beta are importantly all strong candidates as tau kinases that may be involved in the pathogenic hyperphosphorylation of tau in Alzheimer's disease.
SIGNOR-249416
P53779
Q5JR12
1
phosphorylation
down-regulates
0.2
Specific phosphorylation of pp2czeta at ser (92) by stress-activated jnk attenuates its phosphatase activity in cells.
SIGNOR-178926
Q08345
Q06124
1
relocalization
up-regulates activity
0.373
Overexpression of DDR1a/b increased the interaction of DDR1 with SHP-2 and up-regulated the tyrosine phosphatase activity of SHP-2.
SIGNOR-272403
O00257
O60315
1
sumoylation
down-regulates quantity by destabilization
0.331
Pc2 can act directly as an E3 ligase for SIP1 sumoylation.SIP1 sumoylation having a negative effect on its repression of E-cadherin transcription.
SIGNOR-268955
Q15208
Q9UBF8
1
phosphorylation
up-regulates activity
0.267
We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation.
SIGNOR-263033
Q96GD4
Q9UPY8
1
phosphorylation
up-regulates
0.472
Phosphorylation of eb3 at s176 by aurora b ensures successful cytokinesis completion by promoting midbody mt stability and midbody stabilization.
SIGNOR-202130
P27361
P08047
1
phosphorylation
up-regulates
0.653
We showed that perifosine activates the mitogen-activated protein/extracellular signal-regulated kinase pathway, and this activation promotes the phosphorylation of sp1 in known mitogen-activated protein kinase residues (threonine 453 and 739), thereby leading to increased sp1 binding and enhanced p21(waf1/cip1) transcription.
SIGNOR-248062
Q8N122
P53350
0
phosphorylation
up-regulates activity
0.329
Of note, MYC-PLK1 (WT) overexpression strongly enhanced MTOR and RPTOR signals in PLK1 IPs, whereas the LAMP2 signal was strongly decreased (XREF_FIG).|Thus, we conclude that PLK1 can directly phosphorylate RPTOR in vitro.
SIGNOR-279346
P27361
P46527
1
phosphorylation
down-regulates
0.376
These data suggest that increased signaling by erbb receptors up-regulates mapk activity, which, in turn, phosphorylates and destabilizes p27, thus contributing to dysregulated cell cycle progression.
SIGNOR-80234
Q2M3R5
Q8IXL6
0
phosphorylation
up-regulates activity
0.2
Notably, phosphorylation of Stim1 by Fam20C enhances Stim1 activation and store-operated Ca 2+ entry.|We feel that the western blot shows an appropriate range of contrast to support the conclusion that Stim1 can be activated by Fam20C under high calcium conditions.
SIGNOR-280012
P03372
Q16539
0
phosphorylation
up-regulates
0.625
Conversely, constitutively active mkk6 induced p38 mapk activation that recapitulated the effects of polyphenols by inducing eralpha phosphorylation and downstream activation of akt, and enos. The key role of eralpha ser-118 phosphorylation was confirmed in enos-transfected cos-7 cells
SIGNOR-136950
Q06210
Q9UQM7
0
phosphorylation
up-regulates
0.2
Amp-activated protein kinase and calcium/calmodulin-dependent kinase ii were identified to phosphorylate specifically ser243 in vitro. Phosphorylation by these two kinases results in an increase of enzymatic activity by 1.4-fold. These findings suggest for the first time that hgfat1 may be regulated by kinases other than pka.
SIGNOR-158486
O75385
Q9Y4K3
0
ubiquitination
up-regulates quantity by stabilization
0.548
AMBRA1, interacting with the E3-ligase TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its subsequent stabilization, self-association and function.
SIGNOR-273000
Q9Y2Z4
Q2TAL8
0
transcriptional regulation
up-regulates quantity by expression
0.2
QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.
SIGNOR-269413
P08069
Q00987
0
ubiquitination
down-regulates quantity by destabilization
0.66
We could prove that Mdm2 physically associates with IGF-1R and that Mdm2 causes IGF-1R ubiquitination in an in vitro assay.
SIGNOR-278571
P49959
P53350
0
phosphorylation
down-regulates activity
0.2
Plk1 phosphorylates Mre11 at S649.Mre11 phosphorylation at S649/S688 inhibits its binding to dsDNA and antagonizes the ATM signaling.
SIGNOR-265943
P16403
O76064
0
polyubiquitination
down-regulates
0.2
ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2.
SIGNOR-272928
O75385
P62820
0
relocalization
up-regulates activity
0.532
C9orf72 acts as an effector of Rab1a that recruits active Rab1a to theULK1 complex to promote translocation of the ULK1 complex to thephagophore during autophagy initiation
SIGNOR-261299
P48729
P11308
1
phosphorylation
down-regulates quantity by destabilization
0.2
Using in vitro kinase assays, we further demonstrated that deletion of degron 1 largely abolished CKI-mediated phosphorylation of ERG (Figure S5B), indicating that serine residues within degron 1 are the major CKI phosphorylation sites.
SIGNOR-276935
P78536
P15514
1
cleavage
up-regulates activity
0.448
ADAM17 is involved in the release and activation of several growth factors and cytokine receptor ligands. Among the growth factors activated by ADAM17 are TGF-alpha, amphiregulin, epiregulin and HB-EGF
SIGNOR-259842
P0CG48
P09936
0
cleavage
up-regulates quantity
0.864
These data suggest that the physiological role of UCH is to hydrolyze small adducts of ubiquitin and to generate free monomeric ubiquitin from ubiquitin proproteins, but not to deubiquitinate ubiquitin-protein conjugates or disassemble polyubiquitin chains
SIGNOR-249693
P17252
Q05586
1
phosphorylation
up-regulates activity
0.417
Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms. The results show that PKC alpha phosphorylates preferentially S896 and PKC gamma preferentially S890.
SIGNOR-263177
P49841
P12830
1
phosphorylation
up-regulates activity
0.558
Phosphorylation of the E-cadherin Cytoplasmic Domain by CKII and GSK-3β Increases the Binding to β-catenin. pre-phosphorylation by CKII at Ser-855 and/or Ser-853 of E-cadherin is required before GSK-3β can phosphorylate at Ser-849.
SIGNOR-251225
P17948
P63096
1
phosphorylation
up-regulates activity
0.257
RTKs directly phosphorylate Gαi on Y154, 155, and Y320.
SIGNOR-277230
Q04759
Q9BXL7
1
phosphorylation
up-regulates activity
0.775
NF-kappaB activation is triggered by PKCteta-dependent phosphorylation of Carma1 after TCR/CD28 co-stimulation. PKCteta-phosphorylated Carma1 was suggested to function as a molecular scaffold that recruits preassembled Bcl10-Malt1 complexes to the membrane|we demonstrate that PP2A removes PKCteta-dependent phosphorylation of Ser645 in Carma1, and show that maintenance of this phosphorylation is correlated with increased T-cell activation.
SIGNOR-249193
Q9HCE7
Q5VWQ8
1
ubiquitination
down-regulates quantity by destabilization
0.262
DAB2IP protein levels can be negatively regulated by the activity of the E3-ubiquitin ligases Fbw7, Skp2, and Smurf1
SIGNOR-254776
Q14938
A8MYZ6
1
transcriptional regulation
down-regulates quantity
0.2
By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development
SIGNOR-268887
Q92900
P31749
0
phosphorylation
up-regulates activity
0.257
AKT-Mediated UPF1 Phosphorylation at T151 Promotes UPF1 Helicase Activity
SIGNOR-277597
P31249
P08648
1
transcriptional regulation
up-regulates quantity by expression
0.25
The homeobox transcription factor Hox D3 promotes integrin alpha5beta1 expression and function during angiogenesis.
SIGNOR-261649
P12931
Q14118
1
phosphorylation
down-regulates
0.55
Tyrosine 892 is now thought to be the principal site for recognition by the c-src tyrosine kinase;. We show that upon tyrosine phosphorylation, beta-dystroglycan undergoes a profound change in its sub-cellular localization (e.g., from the plasma membrane to an internal membrane compartment). One possibility is that the net negative charge at position 892 causes the redistribution of beta-dystroglycan to this intracellular vesicular location
SIGNOR-101655
Q9H422
Q13158
1
phosphorylation
down-regulates activity
0.436
FIST/HIPK3 causes FADD phosphorylation, thereby promoting FIST/HIPK3-FADD-Fas interaction.  Phosphorylation occurs on Ser194 close to the COOH terminus of human FADD| Fas ligand-induced activation of Jun NH(2)-terminal kinase is impaired by overexpressed active FIST/HIPK3
SIGNOR-251272
O15151
Q93009
0
deubiquitination
up-regulates
0.757
Subsequently, hausp was shown to deubiquitinate mdm2 and mdmx, thereby stabilizing these proteins.
SIGNOR-139453
Q01484
O00533
0
relocalization
up-regulates quantity
0.409
Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.
SIGNOR-266722
P17252
P27987
1
null
down-regulates activity
0.359
However, when assayed in the presence of calcium/calmodulin, the activity of the B isoform was decreased following phosphorylation by either protein kinase.
SIGNOR-248990
P12931
O60716
1
phosphorylation
up-regulates activity
0.922
Identification of Src phosphorylation sites in the catenin p120ctn.Using selected tyrosine to phenylalanine p120 mutants as dominant negative reagents, it may now be possible to selectively block events postulated to be dependent on p120 tyrosine phosphorylation.combinations of Tyr _ Phe mutations at residues 96, 112, 228, 257, 280, 291, 296, and 302
SIGNOR-246484
Q9NZV8
P78411
0
transcriptional regulation
down-regulates quantity by repression
0.487
Irx5 Directly Represses the Kcnd2 Promoter
SIGNOR-266045
P56524
Q13950
1
deacetylation
down-regulates activity
0.524
HDAC4 and HDAC5 deacetylate Runx2, allowing the protein to undergo Smurf-mediated degradation
SIGNOR-227547
P49815
Q13131
0
phosphorylation
up-regulates activity
0.682
However, AMP-activated protein kinase (AMPK), an essential cellular energy sensor, phosphorylates and activates TSC2 [ xref ].
SIGNOR-278981
Q86UE8
Q9Y294
1
phosphorylation
up-regulates quantity by stabilization
0.668
We found that only S192A in hASF1a and S198A in hASF1b significantly affected phosphorylation by hTLK2 | Consistent
SIGNOR-260787
O14746
P00519
0
phosphorylation
down-regulates activity
0.66
These findings indicate that phosphorylation of hTERT by c-Abl is associated with inhibition of telomerase activity.|We also found that c-Abl phosphorylates hTERT and inhibits hTERT activity.
SIGNOR-279354
Q9ULW0
O14965
0
phosphorylation
up-regulates activity
0.965
Here we show that TPX2, a microtubule-bundling protein and activator of Aurora A, plays an important role. TPX2 was phosphorylated by Aurora A during mitosis. Its phospho-null mutant caused short metaphase spindles coupled with low microtubule flux rate. Interestingly, phosphorylation of TPX2 regulated its interaction with CLASP1 but not Kif2a.|This suggests that TPX2 phosphorylation positively regulates the function of CLASP1.| This is in accord with a phosphoproteomics study that identified S121 and S125 as potential phosphorylation sites for Aurora A in mitotic HeLa cells
SIGNOR-265089
P45984
Q14934
1
phosphorylation
up-regulates activity
0.419
Here, we showed that the nuclear factor of activated T3 (NFAT3) is phosphorylated by JNK1 or JNK2 at Ser(213) and Ser(217), which are located in the conserved SP motif.|Moreover, a 3xNFAT-luc reporter gene assay indicated that NFAT3 transcriptional activity was increased in a dose-dependent manner by JNK1 or JNK2.
SIGNOR-280036
P27361
O75582
1
phosphorylation
up-regulates
0.585
In the present study, we show that, in addition to being phosphorylated on thr-581 and ser-360 by erk1/2 or p38, msk1 can autophosphorylate on at least six sites: ser-212, ser-376, ser-381, ser-750, ser-752 and ser-758.
SIGNOR-131379
P01579
Q9UL17
0
transcriptional regulation
up-regulates quantity by expression
0.475
T-bet Transactivates the IFNγ Gene and Represses the IL-2 Gene in EL4 Cells
SIGNOR-266234
Q04206
Q9Y6K9
0
phosphorylation
up-regulates activity
0.862
Chromatographic fractionation of cell extracts allowed the identification of two distinct enzymatic activities phosphorylating ser-536. Peak 1 represents an unknown kinase, whereas peak 2 contained ikkalpha, ikkbeta, ikkepsilon, and tbk1. collectively, our results provide evidence for at least five kinases that converge on ser-536 of p65 and a novel function for this phosphorylation site in the recruitment of components of the basal transcriptional machinery to the interleukin-8 promoter.
SIGNOR-129947
P04637
Q9H2X6
0
phosphorylation
up-regulates
0.797
Based on all these observations, it is legitimate to suggest that axin and daxx seem to adopt both parallel routes and a convergent means to activate p53. In either case, hipk2 seems to be the protein kinase that catalyzes the ser46 phosphorylation.
SIGNOR-151930
P52945
Q13043
0
phosphorylation
down-regulates activity
0.2
MST1 directly phosphorylated PDX1 at Thr11, resulting in its ubiquitination, degradation and impaired insulin secretion.|Thus, kinase activity is required for MST1 induced PDX1 degradation.
SIGNOR-278303
P51608
Q13224
1
transcriptional regulation
down-regulates quantity by repression
0.35
The interaction of MeCP2 with the 2BI3 and 2BI5 sites was strikingly reduced in neurons maintained in the presence of TTX (Fig. 2C). This result is consistent with the classical view of MeCP2 as a general transcriptional repressor, in that the reduced association leads to increased expression of NR2B.
SIGNOR-264685
P35637
P00533
0
phosphorylation
up-regulates activity
0.259
Thus, EGFR appears to mediate FUS nuclear translocation by phosphorylating Y6 and Y296 in FUS.
SIGNOR-279168
Q14938
Q13562
1
transcriptional regulation
up-regulates quantity
0.265
For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)
SIGNOR-268904
P24588
P17612
1
relocalization
up-regulates activity
0.561
In this report, we demonstrate that glutamate receptors and PKA are recruited into a macromolecular signaling complex through direct interaction between the MAGUK proteins, PSD-95 and SAP97, and AKAP79/150
SIGNOR-261292
P29323
Q13224
1
phosphorylation
up-regulates quantity
0.443
In addition, EPHB2 signaling leads to phosphorylation of GluN2B at tyrosine residue 1472 preventing clathrin dependent endocytosis, and increasing the surface retention of GluN2B containing NMDARs.
SIGNOR-279710
Q92833
P15173
1
transcriptional regulation
down-regulates quantity by repression
0.2
JARID2 is a direct target of the PAX3-FOXO1 fusion protein and inhibits myogenic differentiation of rhabdomyosarcoma cells|Addition of Differentiation Media (DM) to human myoblasts was associated with the induction of MYOG, MYOD and MYL1 and a decrease in JARID2 RNA expression|Furthermore, we that showed JARID2 binds to and alters the methylation status of histone H3 lysine 27 in the promoter regions of MYOG and MYL1 and that the interaction of JARID2 at these promoters is dependent upon EED, a core component of the Polycomb Repressive Complex 2 (PRC2). Therefore JARID2 is a downstream effector of PAX3-FOXO1 that maintains an undifferentiated myogenic phenotype that is characteristic of RMS
SIGNOR-249599
Q15831
Q05513
0
phosphorylation
up-regulates
0.321
Here, we have identified s307 as a novel phosphorylation site in lkb1 and provide evidence that, in multiple cell types, phosphorylation of this site by protein kinase c ? (pkc-?) Induces nucleocytoplasmic transport of lkb1.
SIGNOR-185640
Q96FW1
P03372
1
deubiquitination
down-regulates activity
0.546
OTU Domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) deubiquitinates estrogen receptor (ER) alpha and affects ERalpha transcriptional activity.|We show that OTUB1 negatively regulates transcription mediated by ERalpha in transient reporter gene assays and transcription mediated by endogenous ERalpha in Ishikawa endometrial cancer cells.
SIGNOR-276529
Q13586
Q13131
0
phosphorylation
down-regulates activity
0.2
STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE
SIGNOR-277299
P49815
P31749
0
phosphorylation
down-regulates activity
0.817
We demonstrate that, upon activation of PI3K, tuberin is phosphorylated on consensus recognition sites for PI3K-dependent S/T kinases. Moreover, Akt/PKB can phosphorylate tuberin in vitro and in vivo. We also show that S939 and T1462 of tuberin are PI3K-regulated phosphorylation sites and that T1462 is constitutively phosphorylated in PTEN(-/-) tumor-derived cell lines.
SIGNOR-235515
Q96N16
P33176
0
relocalization
up-regulates activity
0.2
Marlin-1 is associated with kinesin-I and suggest that the movement of Marlin-1 is mediated by plus end microtubuledependent molecular motors
SIGNOR-260989
Q8IUC6
Q9Y4K3
0
polyubiquitination
up-regulates
0.83
Here, we show that the TRAF family proteins directly bind TICAM-1 and demonstrate that TRAF2 and TRAF6 bind different sites of the N-terminal TICAM-1 and accelerate its polyubiquitination. we speculate that polyubiquitination of TICAM-1 by TRAF2 and TRAF6 is required for TICAM-1 to induce IRF-3 and NF-κB activation. This is supported by the observation that polyubiquitination of TICAM-1 was required for TRAF3-binding to TICAM-1
SIGNOR-271428
Q9UM73
P23471
0
dephosphorylation
down-regulates
0.545
Rptpbeta/zeta dephosphorylates alk at the site(s) in alk that is undergoing autophosphorylation through autoactivation.
SIGNOR-157227
P19532
Q00534
0
phosphorylation
up-regulates activity
0.2
CDK4 and CDK6 interact with TFEB and TFE3 in the nucleus We next investigated how CDK4 and CDK6 activate TFEB and TFE3 .|CDK4 and CDK6 phosphorylate TFEB and TFE3.
SIGNOR-279517
P00519
P12931
0
phosphorylation
up-regulates activity
0.538
c-Src-induced c-Abl activation involves phosphorylation of Y245 and Y412, two residues required for c-Abl mitogenic function.
SIGNOR-246311
Q6U7Q0
Q01860
1
transcriptional regulation
up-regulates quantity by expression
0.2
Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays revealed that Zfp322a binds to Pou5f1 and Nanog promoters and regulates their transcription.
SIGNOR-264900
P17542
Q9UNE7
0
ubiquitination
down-regulates quantity by destabilization
0.356
Ubiquitination and degradation of Tal1/SCL are induced by notch signaling and depend on Skp2 and CHIP. CHIP promoted Tal1 degradation with both chaperone binding and ubiquitin ligase activities, which are mediated by its TPR domain and U box, respectively.
SIGNOR-271393
Q15067
Q2T9J0
0
cleavage
up-regulates activity
0.694
Here, we demonstrate that Tysnd1, a previously uncharacterized protein, is responsible both for the removal of the leader peptide from PTS2 proteins and for the specific processing of PTS1 proteins. All of the identified Tysnd1 substrates catalyze peroxisomal β-oxidation. In vitro cleavage of Acox1, Scp2 and prethiolase by recombinant Tysnd1.
SIGNOR-261057
Q9H257
P68400
0
phosphorylation
down-regulates activity
0.346
PVHL Acts as an Adaptor to Promote the Inhibitory Phosphorylation of the NF-κB Agonist Card9 by CK2
SIGNOR-257601