IdA
stringlengths
6
21
IdB
stringlengths
6
21
labels
int64
0
2
mechanism
stringclasses
40 values
effect
stringclasses
10 values
score
float64
0.1
0.99
sentence
stringlengths
10
1.63k
signor_id
stringlengths
12
14
Q9P244
P78352
2
binding
up-regulates activity
0.775
SALMs 1-3 contain a C-terminal PDZ-binding motif, which interacts with PSD-95, an abundant postsynaptic scaffolding protein, whereas SALM4 and SALM5 lack PDZ binding. Interactions between SALMs 1–3 and PSD-95 family proteinscould serve a number of functions. SALM1 and SALM2, which lack the ability to interact with a presynaptic ligand and thus cannot be directly targeted to sites of early synaptic adhesion, may require PSD-95 binding for their localization to early synapses.
SIGNOR-264095
P18669
Q8IXJ6
0
deacetylation
up-regulates activity
0.279
Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2.
SIGNOR-266517
Q14934
P27361
0
phosphorylation
up-regulates
0.289
The formation of rsk-nfatc4-dna transcription complex is also apparent upon adipogenesis. Bound rsk phosphorylates ser(676) and potentiates nfatc4 dna binding by escalating nfat-dna association. Ser(676) is also targeted by the erk map kinase, which interacts with nfat at a distinct region than rsk. Thus, integration of the erk/rsk signaling pathway provides a mechanism to modulate nfatc4 transcription activity.
SIGNOR-133276
O43795
P29323
0
phosphorylation
up-regulates activity
0.2
EphB2 kinase activity is required for Myo1b-EphB2 interaction and induced Myo1b phosphorylation.
SIGNOR-279171
O00418
P0DP23
2
binding
up-regulates
0.465
The calmodulin-binding region is located between amino acids 51 and 96
SIGNOR-82505
Q9BYP7
O95198
2
binding
down-regulates quantity by destabilization
0.476
We found that KLHL2, as well as KLHL3, was co-immunoprecipitated with all four WNK isoforms. The direct interaction of KLHL2 with WNKs was confirmed on fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3 and WNK4 within HEK293T cells, and a significant increase of WNK4 ubiquitination by KLHL2 and Cullin3 was observed both in HEK293T cells and in an in vitro ubiquitination assay. These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body.
SIGNOR-272121
P01130
Q12772
0
transcriptional regulation
up-regulates quantity by expression
0.772
Recent studies have demonstrated that PCSK9 mRNA expression was upregulated to a greater extent than that of the LDL receptor in human hepatocytes in primary culture. Our findings also support the role of SREBP-2 as a transcriptional regulator of both the LDL receptor and PCSK9 in human enterocytes.
SIGNOR-254453
Q93008
P62987
1
cleavage
up-regulates quantity
0.611
Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.
SIGNOR-270825
P09471
P08913
2
binding
up-regulates activity
0.397
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
SIGNOR-256977
P12931
Q96KB5
1
phosphorylation
up-regulates quantity by stabilization
0.395
Phosphorylation of TOPK at Y74, Y272 by Src increases the stability of TOPK and promotes tumorigenesis of colon
SIGNOR-277217
Q14332
O75581
2
binding
up-regulates activity
0.667
Here we show that both Fz and Dvl functions are critical for Wnt-induced Lrp6 phosphorylation through Fz-Lrp6 interaction.
SIGNOR-258965
Q9Y2D9
O75081
2
binding
down-regulates activity
0.51
Previously we reported that a classical C2H2 zinc finger DNA binding protein ZNF652 functionally interacts with CBFA2T3 to repress transcription of genes containing ZNF652 consensus DNA binding sequence within the promoters of these target genes.
SIGNOR-253954
P08670
Q13464
0
phosphorylation
down-regulates activity
0.367
We found that vimentin, the most widely expressed intermediate filament protein, served as an excellent substrate for Rho-associated kinase (Rho-kinase) and that vimentin phosphorylated by Rho-kinase lost its ability to form filaments in vitro. Two amino-terminal sites on vimentin, Ser38 and Ser71, were identified as the major phosphorylation sites for Rho-kinase, and Ser71 was the most favored and unique phosphorylation site for Rho-kinase in vitro. 
SIGNOR-248998
P48163
Q96HS1
0
dephosphorylation
up-regulates activity
0.2
PGAM5-mediated dephosphorylation of malic enzyme 1 (ME1) at S336 allows increased ACAT1-mediated K337 acetylation, leading to ME1 dimerization and activation, both of which are reversed by NEK1 kinase-mediated S336 phosphorylation. SIRT6 deacetylase antagonizes ACAT1 function in a manner that involves mutually exclusive ME1 S336 phosphorylation and K337 acetylation.
SIGNOR-275569
P11802
Q02078
2
binding
down-regulates
0.284
In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms.
SIGNOR-176515
Q9Y6N8
P35222
2
binding
up-regulates activity
0.586
At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin
SIGNOR-265850
P16885
P06239
0
phosphorylation
up-regulates
0.558
In vitro phosphorylation experiments with recombinant plcgamma2 and recombinant lck, fyn, and lyn tyrosine kinases showed that phosphorylation of plcgamma2 led to activation of the recombinant enzyme.
SIGNOR-91477
P30086
Q00535
0
phosphorylation
down-regulates quantity by destabilization
0.337
 Here, we demonstrate that RKIP is a substrate of cyclin-dependent kinase 5 (CDK5) in neurons and that the phosphorylation of RKIP at T42 causes the release of Raf-1. Moreover, T42 phosphorylation promotes the exposure and recognition of the target motif "KLYEQ" in the C-terminus of RKIP by chaperone Hsc70 and the subsequent degradation of RKIP via chaperone-mediated autophagy (CMA). 
SIGNOR-276672
P55283
P35222
2
binding
up-regulates activity
0.527
At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin
SIGNOR-265866
P49715
P04150
0
transcriptional regulation
up-regulates quantity by expression
0.455
We show that in addition, DEX-bound GR directly promotes the expression of adipogenic TFs, including C/EBPβ, Klf5, Klf9, and C/EBPα
SIGNOR-256116
O60341
Q04759
0
phosphorylation
down-regulates activity
0.259
Inhibiting PKC-theta also increased the H3K4 demethylase activity of LSD1, indicating that active PKC-theta may prevent LSD1 from demethylating H3K4 and subsequently causing gene repression.|PKC-theta directly phosphorylates LSD1 at serine 111 and regulates its repressive activity and nuclear localization.
SIGNOR-279104
P00519
Q13671
1
phosphorylation
up-regulates
0.751
We also report that the amino-terminal domain of rin1 contains sequences that can mediate interactions with the abl tyrosine kinase and that rin1 is itself tyrosine phosphorylated by c-abl.
SIGNOR-48142
P63092
P29371
2
binding
up-regulates activity
0.2
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.
SIGNOR-256794
Q9Y4D2
Q9UQM7
0
phosphorylation
down-regulates activity
0.2
Activated CaMKII interacted with the C-terminal domain of DGLalpha, phosphorylated two serine residues and inhibited DGLalpha activity. |CaMKIIalpha phosphorylates DGLalpha at Ser808 and Ser782
SIGNOR-275540
Q13017
P61586
1
gtpase-activating protein
down-regulates activity
0.828
We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).
SIGNOR-260461
P49841
O75925
1
phosphorylation
down-regulates quantity by destabilization
0.332
We discovered a ubiquitin E3 ligase, HECTD2, which ubiquitinated and mediated the degradation of PIAS1, thus increasing inflammation in an experimental pneumonia model. We found that GSK3β phosphorylation of PIAS1 provided a phosphodegron for HECTD2 targeting. 
SIGNOR-276923
P40337
O14965
0
phosphorylation
down-regulates quantity by destabilization
0.406
Conversely, AURKA can phosphorylate VHL at serine 72, a priming phosphorylation for GSK3beta, which regulates VHL 's role in microtubule stability.
SIGNOR-279800
P03372
O15111
0
phosphorylation
up-regulates activity
0.47
These results demonstrated an estrogen-mediated increase in the phosphorylation of ER\u03b1 at serine residue 118 by IKK\u03b1 ( Figure 5 H, bottom).|Wt IKKalpha, but not the IKKalpha kinase mutant, increased both estrogen dependent and -independent ERalpha activation.
SIGNOR-279696
P62753
P23443
0
phosphorylation
up-regulates activity
0.937
A knockin mouse carrying mutations at all phosphorylation sites in the primary s6k substrate, ribosomal protein s6 (rps6), has provided insight into the physiological role of this protein phosphorylation event. Of the many known substrates of s6k1, it is rps6 that has been shown to be directly involved, via its phosphorylation, in controlling cell size.
SIGNOR-135176
P34925
Q92997
2
binding
up-regulates
0.403
Ryk also binds to dishevelled, through which it activates the canonical wnt, providing a link between wnt and dishevelled
SIGNOR-129574
Q16539
P06239
0
phosphorylation
up-regulates activity
0.475
Lck, Fyn, and Zap70 activate p38 even in the absence of Tyr182 phosphorylation.p38 is a substrate for Fyn, Lck and Zap70.Thus, T cell Src family kinases and Zap70 activate p38 by phosphorylating Tyr323.
SIGNOR-276029
P30307
P45983
0
phosphorylation
down-regulates
0.411
Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset.
SIGNOR-164089
P29353
P06239
0
phosphorylation
up-regulates activity
0.744
We show that during TCR signaling, the tyrosines Y239, Y240 and Y317 of Shc are the primary sites of tyrosine phosphorylation. CD4/Lck-dependent tyrosine phosphorylation on Shc was markedly diminished when Y317 was mutated, suggesting a preference of Lck for the Y317 site. tyrosine phosphorylation of Shc may play a key role in T lymphocyte proliferation via interaction of phosphorylated Shc with downstream molecules involved in activation of Ras and Myc proteins
SIGNOR-251388
P00533
Q06124
2
phosphorylation
up-regulates activity
0.87
EGFRvIII transformation may be due to the enhanced PTPase activity from higher basal SHP-2 Tyr542 phosphorylation induced by EGFRvIII ( xref ).|These results suggest that EGFRvIII expression recruits SHP-2 to an activated complex and induces SHP-2 Tyr542 and its PTPase activity in GBM cells.
SIGNOR-279460
Q96ED9
Q7Z7A1
2
binding
up-regulates
0.353
Hook2 localizes to the centrosome, binds directly to centriolin/cep110 and contributes to centrosomal function
SIGNOR-150956
P11362
P00338
1
phosphorylation
up-regulates
0.366
We found that the oncogenic receptor tyrosine kinase fgfr1 directly phosphorylates ldh-a. Phosphorylation at y10 and y83 enhances ldh-a activity by enhancing the formation of active, tetrameric ldh-a and the binding of ldh-a substrate nadh, respectively.
SIGNOR-176730
P18031
P78337
1
dephosphorylation
down-regulates quantity by destabilization
0.354
PTP1B dephosphorylates PITX-1 at Y160, 175 and Y179.|Through directly dephosphorylating PITX-1 at Y160, Y175 and Y179, PTP1B promoted proteasomal degradation of PITX-1, thus leaded in downregulating p120RasGAP and CRC cell survival.
SIGNOR-276973
O75113
P46934
0
monoubiquitination
up-regulates activity
0.448
This observation, together with the monoubiquitination of Nedd4-BP1 by the ubiquitin ligase Nedd4 suggests that the NYN domain proteins of eukaryotes are regulated by monoubiquitination. Given the localization of Nedd4-BP1 to punctuate nuclear bodies, it is likely that they are parts of nuclear RNA-processing complexes that are dependent on monoubiquitination for their assembly.
SIGNOR-272626
P14778
O43187
2
binding
up-regulates activity
0.697
Two additional proximal mediators were identified that are required for IL-1R–induced NF-κB activation: IRAK-2, a Pelle family member, and MyD88, a death domain–containing adapter molecule. IRAK-2 preferentially bound IL-1RI. A truncated version of IRAK-2 that lacked the first 96 amino acids [IRAK-2(97-590)] did not associate with IL-1RI, which suggests that the NH2-terminal segment docks with the cytoplasmic domain of IL-1RI.
SIGNOR-273854
Q99828
Q9UNE7
0
ubiquitination
down-regulates quantity
0.2
All those were suggesting that CHIP promotes CIB1 ubiquitination via the Lys 48 residue of ubiquitin.|K10 and K65 were the Lysine (K) residues for CHIP mediated CIB1 degradation.
SIGNOR-278721
P54760
P98172
2
binding
up-regulates
0.754
Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor
SIGNOR-52580
P41143
P25098
0
phosphorylation
down-regulates activity
0.2
Taken together, we have demonstrated that agonist-induced opioid receptor phosphorylation occurs exclusively at two phosphate acceptor sites (T358 and S363) of GRK2 at the DOR carboxyl terminus.
SIGNOR-249660
Q9UM11
Q16763
2
binding
up-regulates activity
0.761
Ube2S depends on the cell cycle-dependent association with the APC/C activators Cdc20 and Cdh1 for its activity
SIGNOR-265081
P06493
P04183
1
phosphorylation
down-regulates
0.507
Given that the dimeric form of tk1 is less active than the tetrameric, we propose that mitotic phosphorylation of serine-13 is of physiological importance, in that it may counteract atp-dependent activation of tk1 by affecting its quaternary structure, thus attenuating its enzymatic function at the g2/m phase.
SIGNOR-95574
Q86YC2
Q06609
2
binding
up-regulates
0.753
We propose that both palb2 chromatin association and its oligomerization serve to secure the brca2 x rad51 repair machinery at the sites of dna damage.
SIGNOR-185656
P01375
P20333
2
binding
up-regulates activity
0.93
The binding of tnf to tnf-r1 triggers a series of intracellular events that ultimately result in the activation of two major transcription factors, nuclear factor kb (nf-kb) and c-jun.
SIGNOR-88216
Q14814
Q16539
0
phosphorylation
up-regulates activity
0.612
Targeting of ash2l to specific genes is mediated by the transcriptional regulator mef2d. Furthermore, this interaction is modulated during differentiation through activation of the p38 mapk signaling pathway via phosphorylation of mef2d.
SIGNOR-159331
P27361
P28562
2
phosphorylation
up-regulates
0.786
Mkp-1 was a target in vivo and in vitro for p42(mapk) or p44(mapk), which phosphorylates mkp-1 on two carboxyl-terminal serine residues, serine 359 and serine 364. This phosphorylation did not modify mkp-1's intrinsic ability to dephosphorylate p44(mapk) but led to stabilization of the protein.
SIGNOR-73633
P19544
O60500
1
transcriptional regulation
up-regulates quantity by expression
0.487
The Wilms tumor suppressor gene (WT1) is a zinc-finger-containing transcription factor that is coexpressed with NPHS1 in differentiated podocytes; gel shift binding assays demonstrate that a recombinant WT1 protein can bind and activate the 186-bp NPHS1 fragment in a sequence-specific manner
SIGNOR-252299
Q07812
Q9NR28
1
relocalization
up-regulates
0.545
Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi
SIGNOR-87109
Q03113
P47900
2
binding
up-regulates activity
0.2
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
SIGNOR-257394
P12931
P22001
1
phosphorylation
up-regulates
0.31
The shaker family k+ channel protein, kv1.3, is tyrosine phosphorylated by v-src kinase at tyr137 and tyr449 to modulate current magnitude and kinetic properties.
SIGNOR-114641
P63162
O15355
0
dephosphorylation
up-regulates quantity by stabilization
0.2
Dephosphorylation of survival motor neurons (SMN) by PPM1G and PP2Cgamma governs Cajal body localization and stability of the SMN complex.|This indicates that the catalytic activity of PPM1G promotes accumulation of the SMN complex in CBs and suggests that PPM1G is a major determinant of the SMN-complex localization in the nucleus.
SIGNOR-277021
P11802
Q92830
1
phosphorylation
up-regulates activity
0.36
Activated cyclin D1-Cdk4 kinase phosphorylates and activates GCN5|GCN5 T272A/S372A (AA) phosphorylation by cyclin D1-CDK4 kinase is diminished compared to GCN5 wild-type (WT)
SIGNOR-275494
Q9BXM7
Q6NUN9
1
phosphorylation
up-regulates activity
0.37
PINK1 directly phosphorylates PARIS at S322 and S613, priming it for ubiquitination by Parkin, which interacts with the C-terminus zinc finger of PARIS and tags it for destruction [ xref \u2013 xref , xref ].|Thus, by tagging PARIS for destruction, PINK1/Parkin drive the generation of new mitochondria by increasing PGC-1\u03b1 levels (Fig. 1d).
SIGNOR-278268
Q86WV6
Q99942
0
ubiquitination
down-regulates quantity by destabilization
0.2
The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA. RNF5 targeted MITA at Lys150 for ubiquitination and degradation after viral infection.
SIGNOR-271484
P09471
Q15077
2
binding
up-regulates activity
0.2
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
SIGNOR-257076
Q14164
O43734
1
phosphorylation
up-regulates activity
0.416
IKKi was required for IL-17-induced phosphorylation of Act1 on Ser311, adjacent to a putative TRAF-binding motif. Substitution of the serine at position 311 with alanine impaired the IL-17-mediated Act1-TRAF2-TRAF5 interaction and gene expression. Thus, IKKi is a kinase newly identified as modulating IL-17 signaling through its effect on Act1 phosphorylation and consequent function.
SIGNOR-262883
O75925
O15111
0
phosphorylation
up-regulates activity
0.38
In addition, we show that IKKalpha is associated with PIAS1 and mediates the S90 phosphorylation of PIAS1.|Mutational studies indicate that Ser90 phosphorylation is required for PIAS1 to repress transcription.
SIGNOR-278926
Q92530
Q9H2K2
0
ADP-ribosylation
down-regulates quantity by destabilization
0.496
We identify the ADP-ribosyltransferase tankyrase (TNKS) and the 19S assembly chaperones dp27 and dS5b as direct binding partners of the proteasome regulator PI31. TNKS-mediated ADP-ribosylation of PI31 drastically reduces its affinity for 20S proteasome alpha subunits to relieve 20S repression by PI31.
SIGNOR-263386
Q96GD4
Q96FF9
1
phosphorylation
down-regulates activity
0.629
Here we show that the mitotic kinases Aurora B and Cyclin-dependent kinase 1 (Cdk1) destabilize interactions between Sororin and the cohesin subunit precocious dissociation of sisters protein 5 (Pds5) by phosphorylating Sororin, leading to release of acetylated cohesin from chromosome arms and loss of cohesion. 
SIGNOR-276116
Q16891
Q9BXM7
2
binding
up-regulates activity
0.4
MIC60 Is Crucial for Parkin Recruitment and Transiently Interacts with PINK1
SIGNOR-266301
Q9ULV4
P68400
0
phosphorylation
up-regulates
0.2
We demonstrate that crn2 is a binding partner and substrate of protein kinase ck2, which phosphorylates crn2 at s463 in its c-terminal coiled coil domain
SIGNOR-196193
Q9BUZ4
Q9HAU4
1
ubiquitination
down-regulates quantity by destabilization
0.361
TRAF4 acts as an E3 ubiquitin ligase to ubiquitinate the K119 site of Smurf2 through the K48 ubiquitin chain and degrade Smurf2.
SIGNOR-278617
O95644
P17612
0
phosphorylation
down-regulates
0.385
Here we show that overexpression of pka causes phosphorylation and cytoplasmic accumulation of nf-atc1 in direct opposition to calcineurin by phosphorylating ser-245, ser-269, and ser-294 in the conserved serine-proline repeat domainwe further show that a complete block of nf-atc1 nuclear localization by pka requires a second kinase activity that can be supplied by glycogen synthase kinase-3 (gsk-3)
SIGNOR-93531
P28482
Q9UKX7
1
phosphorylation
down-regulates activity
0.2
Erk phosphorylates nup50 at ser221 and ser315 erk phosphorylation of the fg repeat region of nup50 reduced its affinity for importin-beta family proteins, importin-beta and transportin.
SIGNOR-188135
P35222
P51955
0
phosphorylation
down-regulates quantity
0.469
NEK2 silencing reduced the phosphorylation of beta-catenin at Ser33 and Ser37, but did not decrease the level of total beta-catenin.|NEK2 slightly decreased the level of total beta-catenin (XREF_FIG).
SIGNOR-278173
P00533
P0DP25
1
phosphorylation
down-regulates
0.382
Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.
SIGNOR-266335
Q02930
Q02930
2
binding
up-regulates activity
0.2
CRE-BPa specifically binds to CRE as a homodimer or heterodimer with c-Jun or CRE-BP1. In CAT cotransfection experiments using CV-1 cells, transient expression of each of four CRE-BPa proteins caused a 1.6- to 3.4-fold increase of CRE-dependent transcription
SIGNOR-219602
Q9Y5F7
Q9Y5I2
2
binding
up-regulates activity
0.2
The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.
SIGNOR-265715
P46821
P49841
0
phosphorylation
down-regulates activity
0.527
GSK-3beta phosphorylates MAP1B and the adenomatous polyposis coil gene product (APC; Grimes and Jope 2001; Frame and Cohen 2001). The phosphorylation of MAP1B by GSK-3beta suppresses detyrosination of microtubules and decreases the numbers of stable microtubules
SIGNOR-264843
Q9BV47
P04629
1
dephosphorylation
down-regulates activity
0.371
NEAP and DUSP26 dephosphorylated TrkA and FGFR1 directly.|We found that NEAP, but not its phosphatase-defective mutant, suppressed nerve growth factor (NGF) receptor TrkA and fibroblast growth factor receptor 1 (FGFR1) activation in PC12 cells
SIGNOR-277105
P17600
Q00535
0
phosphorylation
up-regulates
0.563
Synapsin i (syni), a major sv phosphoprotein involved in the regulation of sv trafficking and neurotransmitter release, is one of the presynaptic substrates of cdk5, which phosphorylates it in its c-terminal region at ser(549) (site 6) and ser(551) (site 7). Phosphorylation of syni by cdk5 is physiologically regulated and enhances its binding to f-actin.
SIGNOR-78883
P19086
P28336
2
binding
up-regulates activity
0.25
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
SIGNOR-257315
Q8IUQ4
P46531
1
relocalization
up-regulates
0.26
The overexpression of siah1 causes the re-localization of notch from the cell surface to the cytoplasm and to the nucleus, which is indicative of notch activation
SIGNOR-168460
Q02363
Q9Y463
0
phosphorylation
down-regulates activity
0.2
Phosphorylation of Thr27 of ID2 by DYRK1 blocks ID2-VHL interaction and preserves HIF2α ubiquitylation.|We report that DYRK1A and DYRK1B kinases phosphorylate ID2 on Threonine-27 (T27).
SIGNOR-279033
Q13464
O00429
1
phosphorylation
up-regulates activity
0.314
We have also previously reported that ROCK1-mediated Drp1S600 phosphorylation resulted in enhanced mitochondrial fission in podocytes
SIGNOR-262549
P57764
P51878
0
cleavage
up-regulates activity
0.62
Co-expression of GSDMD with caspase-1, 4, 5 or 11 but not apoptotic caspases (caspase-2, 8 and 9) in 293T cells induced the same cleavage of GSDMD|inflammatory caspases specifically cleave GSDMD after the 272FLTD275 (or 273LLSD276) sequence |
SIGNOR-256418
Q13535
Q96RU2
1
phosphorylation
up-regulates activity
0.2
Here we report that the deubiquitylase USP28 is recruited to sites of DNA damage in cisplatin-treated cells. ATR phosphorylates USP28 and increases its enzymatic activity.|Representative immunoblots of n = 3. C Immunoblotting of total and phosphorylated USP28 at serine 67 and 714 in A431 cells exposed to indicated concentrations of CPPD for 6 h.
SIGNOR-275850
P06493
O95835
1
phosphorylation
up-regulates
0.389
Warts is a serine/threonine kinase and a dynamic component of the mitotic apparatus. We have found that cdc2/cyclin b forms a complex with a fraction of warts in the centrosome and phosphorylates the ser613 site of warts during mitosisit can be speculated that phosphorylation of warts by cdc2/cyclin b promotes a protein complex formation on the mitotic apparatus at early mitosis, which may be required for subsequent activation of warts kinase at the metaphase-anaphase transition.
SIGNOR-94160
P78352
P06241
0
phosphorylation
up-regulates
0.562
Psd-95 is phosphorylated either by purified src/fyn kinases in vitro or by co-expression of constitutively active src/fyn in cos7 cells. psd-95 tyr(523) phosphorylation contributes to the post-ischaemic over-activation of nmda receptors.
SIGNOR-180449
Q16539
P45985
0
phosphorylation
up-regulates activity
0.591
Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase.
SIGNOR-34121
P45983
Q13363
1
phosphorylation
down-regulates
0.358
In this study, we found that c-jun nh2-terminal kinase 1 activation triggered ctbp phosphorylation on ser-422 and subsequent degradation,
SIGNOR-149721
P28482
P33076
1
phosphorylation
up-regulates
0.432
We show in this study that the nuclear localized form of ciita is a predominantly phosphorylated form of the protein, whereas cytoplasmic ciita is predominantly unphosphorylated. Novel phosphorylation sites were determined to be located within a region that contains serine residues 286, 288, and 293. Double mutations of these residues increased nuclear ciita, indicating that these sites are not required for nuclear import. Erk1/2-mediated phosphorylation of ciita down-regulates ciita activity by priming it for nuclear export, thus providing a means for cells to tightly regulate the extent of antigen presentation.
SIGNOR-160609
P42345
O75143
1
phosphorylation
down-regulates
0.651
Mtor phosphorylates a mammalian homologue of atg13 and the mammalian atg1 homologues ulk1 and ulk2.
SIGNOR-183965
Q99717
Q9UNE7
0
ubiquitination
down-regulates
0.343
In ad-dition, some proteins (e.g. Chip, carboxyl terminus of hsc70-interacting protein) inhibit the signaling activi-ties of smad1/5 by recruiting smad1/5 from the functional r-/co-smad complex and further pro-moting the ubiquitination and degradation of smad1/5 in a chaperone-independent manne
SIGNOR-195690
P61586
Q13017
0
gtpase-activating protein
down-regulates activity
0.828
We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).
SIGNOR-260461
P78352
Q00535
0
phosphorylation
down-regulates activity
0.655
Cdk5 was shown to phosphorylate PSD-95 at three sites, Thr19, Ser25, and Ser35, in PSD fractions, which reduces the ability of PSD-95 to multimerize, resulting in decreased NMDAR clustering (Table 2).
SIGNOR-279152
Q9NRR4
P49841
0
phosphorylation
up-regulates activity
0.278
Our findings suggest that phosphorylation of Drosha at multiple sites including S300 promotes its translocation to the cytoplasm. Interestingly, GSK3beta can phosphorylate Drosha at S300 and S302 in vitro. This has been reported to promote the nuclear localization of Drosha under basal condition (Tang et al., 2011). Thus, it appears that phosphorylation of S300 by GSK3beta and p38 MAPK is involved in opposing processes. 
SIGNOR-264846
Q13131
Q16526
1
phosphorylation
down-regulates
0.384
Ampk was shown to regulate the stability of the core clock component cry1 though phosphorylation of cry1 ser71, which stimulates the direct binding of the fbox protein fbxl3 to cry1, targeting it for ubiquitin-mediated degradation
SIGNOR-176472
Q9NQ66
P30679
2
binding
up-regulates activity
0.484
This suggests that both Gal4 and Gal6 can activate PLC b1.
SIGNOR-278120
Q9UBK2
P78527
0
phosphorylation
down-regulates quantity by destabilization
0.2
Mechanistically, PGC1α was phosphorylated at serine (S) 636 by DNA-dependent protein kinase in response to irradiation. Phosphorylation at S636 promoted the degradation of PGC1α by facilitating its binding to the E3 ligase RNF34. 
SIGNOR-277911
P12931
P29353
1
phosphorylation
up-regulates activity
0.666
Here, we report the identification of two major and novel Shc tyrosine phosphorylation sites, Y239 and Y240. Y239/240 are co-ordinately phosphorylated by the src protein-tyrosine kinase in vitro, and in response to epidermal growth factor stimulation or in v-src-transformed cells in vivo. phosphorylation of y317 has been implicated in grb2 binding and activation of the ras pathway.
SIGNOR-44870
Q9NYY3
Q9Y4G8
1
phosphorylation
up-regulates activity
0.357
Here, we report that Plk2 phosphorylates a quartet of Ras and Rap regulators : SynGAP, PDZGEF1, RasGRF1 and SPAR, resulting in powerful bidirectional control over Rap and Ras activity.|Thus, Plk2 was sufficient to promote the activities of both SynGAP and PDZGEF1 in mammalian cells.
SIGNOR-280066
P50148
Q9BPV8
2
binding
up-regulates activity
0.2
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.
SIGNOR-256892
P19784
O95786
1
phosphorylation
down-regulates activity
0.2
Phosphorylation of RIG-I by casein kinase II inhibits its antiviral response.Threonine at amino acid (aa) 770 and serine at aa 854 to 855 of RIG-I are phosphorylated by casein kinase II (CK2) in the resting state of the cell and dephosphorylated when cells are infected by RNA virus.
SIGNOR-276285
Q9HAW4
O75717
2
binding
up-regulates activity
0.392
And-1 is phosphorylated at T826 by ATR following replication stress, and this phosphorylation is required for And-1 to accumulate at the damage sites, where And-1 promotes the interaction between Claspin and Chk1, thereby stimulating efficient Chk1 activation by ATR. Significantly, And-1 binds directly to ssDNA and facilitates the association of Claspin with ssDNA.
SIGNOR-262665
P38936
P15173
0
transcriptional regulation
down-regulates quantity by repression
0.331
P21 is regulated by MyoD and myogenin in normal muscle cells and the inactivation of these factors in RMS cells contributes to the silencing of p21 in RMS cells
SIGNOR-251575
Q9UBI6
P42336
2
binding
up-regulates
0.4
We show that pge2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (g protein)coupled receptor, ep2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase akt by free g protein bg subunits and the direct association of the g protein as subunit with the regulator of g protein signaling (rgs) domain of axin.
SIGNOR-141795
Q9Y210
P12931
0
phosphorylation
up-regulates activity
0.435
TRPC6 Y31 and Y284 are phosphorylated by Src family kinase in isolated glomeruli.
SIGNOR-279659