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P19474
P49915
1
ubiquitination
down-regulates
0.326
Cytoplasmic sequestration of gmps requires ubiquitylation by trim21, a ubiquitin ligase associated with autoimmune disease.
SIGNOR-204478
P63096
Q8IYL9
2
binding
up-regulates activity
0.271
GPR65 is playing a critical role in phagocytic cells that require high levels of V-ATPase activity to maintain phagosomal and lysosomal pH, and this activity aids in the direct clearance of enteric pathogens.
SIGNOR-272502
P46940
Q02156
0
phosphorylation
up-regulates
0.2
Using a mass spectrometry-based assay, we show that egf induces phosphorylation of iqgap1 ser(1443), a residue known to be phosphorylated by pkcthe nonphosphorylatable iqgap1 s1441a/s1443a had no effect. In contrast, the s1441e/s1443d mutation markedly enhanced the ability of iqgap1 to induce neurite outgrowth.
SIGNOR-128718
P49356
P01112
1
null
up-regulates activity
0.46
Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials.
SIGNOR-242565
P50148
Q9NZN5
2
binding
up-regulates activity
0.419
Leukemia-associated Rho guanine nucleotide exchange factor promotes G alpha q-coupled activation of RhoA.
SIGNOR-256520
P84243
P45973
2
binding
up-regulates activity
0.2
A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing.
SIGNOR-264488
Q9UJX3
Q9UKT4
2
binding
down-regulates
0.458
Emi1 can inhibit apc already activated by cdc20 or cdh1.
SIGNOR-113382
P28566
P09471
2
binding
up-regulates activity
0.378
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-256984
Q9NR61
Q86YT6
0
ubiquitination
up-regulates activity
0.553
Mib physically interacts with Delta and promotes its ubiquitination and internalization [66], which have been shown to up-regulate Notch activity.
SIGNOR-209626
P37288
P38405
2
binding
up-regulates activity
0.271
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-256948
O43164
P13861
1
polyubiquitination
down-regulates quantity by destabilization
0.328
Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits
SIGNOR-271856
Q00613
P31751
0
phosphorylation
up-regulates activity
0.309
AKT2 also phosphorylated S326 of HSF1 but showed weak ability to activate HSF1.|AKT2 promoted a significant increase in HSF1 activity , but the effect was modest while AKT3 had no significant effect on HSF1 activity ( Fig. 1A-C ) .
SIGNOR-279779
P05556
Q9UN74
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.
SIGNOR-265665
Q04724
P68400
0
phosphorylation
up-regulates
0.32
These results suggest that ck2 phosphorylation of serine 239 of gro/tle1 is important for its function during neuronal differentiation.
SIGNOR-129026
Q15154
O15182
1
relocalization
up-regulates
0.297
Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome
SIGNOR-95016
P46934
Q9HC16
1
ubiquitination
up-regulates activity
0.284
APOBEC3G ubiquitination by Nedd4-1 favors its packaging into HIV-1 particles|This could be explained in at least two ways : first, endogenous Nedd4 is naturally expressed at a level largely sufficient to target APOBEC3G into the VLP or virions.
SIGNOR-278635
P19793
P10827
2
binding
up-regulates
0.663
Like many receptors belonging to the superfamily of steroid/thyroid nuclear receptors, thyroid hormone receptors (trs) bind to specific th-dna responsive elements (tre) upstream of target gene in heterodimeric complex with the 9-cis retinoid acid receptor (rxr).
SIGNOR-81446
P42338
P01112
2
binding
up-regulates activity
0.759
Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85. it was also described that ras interacts with pi3k in a direct manner.
SIGNOR-175189
Q6W2J9
O15379
2
binding
up-regulates activity
0.313
BCoR can interact w Because HDACs appear to be involved in repression by an increasing number of transcriptional repressors, we tested whether BCoR can associate with HDACs. BCoR can interact with HDAC1, HDAC3, and HDAC-B/5 more strongly than with HDAC-A/4, HDAC-C, HDAC-D, and HDAC-E.
SIGNOR-252237
P35398
Q14643
1
transcriptional regulation
up-regulates quantity by expression
0.242
RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.
SIGNOR-266847
P35568
Q13526
0
isomerization
up-regulates activity
0.2
In this study, the association of Par14 with insulin receptor substrate 1 (IRS-1) was demonstrated in HepG2 cells|Therefore, although Pin1 and Par14 associate with different portions of IRS-1, the prolyl cis/trans isomerization in multiple sites of IRS-1 by these isomerases appears to be critical for efficient insulin receptor-induced IRS-1 phosphorylation|Par14 overexpression in HepG2 markedly enhanced insulin-induced IRS-1 phosphorylation and its downstream events
SIGNOR-265757
Q8TEP8
O14965
2
binding
up-regulates activity
0.796
These findings demonstrated that Cep192 mediates the AurA-Plk1 interaction and that the formation of the Cep192-AurA-Plk1 complex could be important for activating AurA and Plk1.
SIGNOR-266406
P30542
Q9ULU4
0
transcriptional regulation
up-regulates quantity by expression
0.2
We also confirmed transcriptional coactivator functions of ZMYND8 in ERα-driven reporter assays and on endogenous E2-dependent genes (Figure 5F,G). siRNA knockdown of ZMYND8 showed markedly decreased transcription at the presumptive ERα/Z3 target genes ADORA1 and NAV2, while the classical ERα targets pS2/TFF1 and GREB1 appear to be less affected (Figure 5G), suggesting likely gene-specificity of ZMYND8. 
SIGNOR-266208
Q15653
Q15418
0
phosphorylation
down-regulates quantity by destabilization
0.369
By using recombinant wild-type and mutant IkappaBbeta proteins, both active ERK2 and RSK1 were found to directly phosphorylate IkappaBbeta, but only active RSK1 phosphorylated IkappaBbeta on Ser19 and Ser23, two sites known to mediate the subsequent ubiquitination and degradation.
SIGNOR-280114
P49840
P24071
1
phosphorylation
down-regulates activity
0.2
GSK-3 is constitutively active in the absence of cytokine stimulation and can phosphorylate S263, keeping FcalphaRI in the inactive state.
SIGNOR-264856
O75348
P0C6X7-PRO_0000037312
0
cleavage
down-regulates activity
0.2
Cleavage of the V-ATPase G1 fusion protein by SARS-CoV 3CLpro was found in this study (Fig. 3), implying that 3CLpro potentially cleaves the cellular V-ATPase G1, and affects the function of vacuolar H(+)-ATPase. Meanwhile, a significant intracellular acidification has been demonstrated in the 3CLpro-expressing cells (Fig. 4D). The result correlated well with previous reports in that V-ATPase-specific inhibitors cause acidic pHi [28], [29], and influences cell apoptosis
SIGNOR-260264
P67775
Q9H0H5
1
dephosphorylation
down-regulates
0.303
We report here that (i) mgcracgap is phosphorylated by aurora b and cdk1, (ii) pp2a dephosphorylates aurora b and cdk1 phosphorylated sites and (iii) inhibition of pp2a abrogates mgcracgap/ect2 interaction. Therefore, pp2a may regulate cytokinesis by dephosphorylating mgcracgap and its interacting partners.
SIGNOR-160398
O95295
O43567
0
polyubiquitination
up-regulates activity
0.521
 RNF13 directly interacted with snapin, a SNAP-25-interacting protein. Interestingly, snapin was ubiquitinated by RNF13 via the lysine-29 conjugated polyubiquitin chain, which in turn promoted the association of snapin with SNAP-25. Consistently, we found an attenuated interaction between snapin and SNAP-25 in the RNF13-null mice. Therefore, these results suggest that RNF13 is involved in the regulation of the SNARE complex, which thereby controls synaptic function.
SIGNOR-272044
Q86Z02
P10242
1
phosphorylation
down-regulates activity
0.2
C-Myb appears to be phosphorylated by HIPK1 in its negative regulatory domain as supported by both in vivo and in vitro data.
SIGNOR-279189
P61586
Q5TG30
0
gtpase-activating protein
down-regulates activity
0.432
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-260496
Q14980
P07437
2
binding
up-regulates
0.404
Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.
SIGNOR-116900
P29692
Q13683
1
transcriptional regulation
down-regulates quantity by repression
0.2
alpha7 Integrin Expression Is Negatively Regulated by deltaEF1 during Skeletal Myogenesis
SIGNOR-241773
P37023
Q9UK05
2
binding
up-regulates
0.907
Finally, we demonstrate that bmp9 and bmp10 potently inhibit endothelial cell migration and growth, and stimulate endothelial expression of a panel of genes that was previously reported to be activated by the constitutively active form of alk1. Taken together, our results suggest that bmp9 and bmp10 are two specific alk1 ligands that may physiologically trigger the effects of alk1 on angiogenesis.
SIGNOR-150260
Q13625
P28482
0
phosphorylation
up-regulates activity
0.263
Hence ASPP2 can be phosphorylated at serine 827 by MAPK1 in vitro.|Phosphorylation of ASPP2 by MAPK is required for RAS-induced increased binding to p53 and increased transactivation of pro-apoptotic genes.
SIGNOR-264414
Q9HBM1
P35579
2
binding
up-regulates activity
0.2
This study demonstrates that SPC25 acts as a molecular scaffold, mediating SPC25/RIOK1/MYH9 complex formation and triggering the RIOK1‐mediated phosphorylation of MYH9 at Ser1943.Taken together, these results suggested that SPC25 increases MYH9 phosphorylation at Ser1943, enhancing the nuclear accumulation of MYH9 and consequently modulating the transcription of CTNNB1.
SIGNOR-278894
P45983
Q99640
1
phosphorylation
up-regulates
0.336
A kinase assay using gst-myt1 revealed that active jnk1 or jnk3, but not jnk2, phosphorylated myt1 in vitro.
SIGNOR-183899
Q8NHM5
Q16665
0
transcriptional regulation
up-regulates quantity by expression
0.2
To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.
SIGNOR-271567
P31749
Q96RU7
2
binding
down-regulates activity
0.619
TRB3 expression is induced in liver under fasting conditions, and TRB3 disrupts insulin signaling by binding directly to Akt and blocking activation of the kinase.
SIGNOR-252644
Q6GPH4
Q13489
2
binding
down-regulates
0.391
Immunoprecipitation studies indicate that xaf1 binds to xiap,birc2,birc3
SIGNOR-155288
P51451
P16885
1
phosphorylation
up-regulates activity
0.557
Lyn, Syk, Btk, and Blk can also phosphorylate and enhance the activation of phospholipase C gamma 2 (PLCgamma2), which hydrolyzes PI (4,5) P2 to create inositol 3,4,5-trisphosphate (IP3) and diacylglycerol (DAG), stimulating Ca 2+ mobilization and protein kinase C (PKC), respectively.
SIGNOR-280195
P15172
P41134
2
binding
down-regulates activity
0.478
Id1 and Id2 interacted strongly with MyoD and Myf-5.Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo.
SIGNOR-240265
P04049
Q969H4
2
binding
up-regulates
0.71
Here we demonstrate that the connector enhancer of ksr1, cnk1, mediates src-dependent tyrosine phosphorylation and activation of raf-1. Cnk1 binds preactivated raf-1 and activated src and forms a trimeric complex.
SIGNOR-135674
P33527
P68400
0
phosphorylation
up-regulates
0.374
Casein kinase 2_ regulates multidrug resistance-associated protein 1 function via phosphorylation of thr249. This study supports a model in which ck2_ potentiates mrp1 function via direct phosphorylation of thr249.
SIGNOR-197844
P49841
O75474
2
binding
down-regulates activity
0.695
The structure of phosphorylated GSK-3beta complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation.
SIGNOR-244030
O43379
P45985
1
relocalization
up-regulates activity
0.2
In the WT brain, the WDR62 scaffold organizes a protein complex including MEKK3, MKK4/7, and JNK1 to control NPC development during corticogenesis
SIGNOR-271715
P31751
O15530
0
phosphorylation
up-regulates activity
0.732
Akt1 and akt2 are phosphorylated and activated by the protein kinase pdk1 at thr-308 or thr-309, respectively, in the activation t-loop, and further activation occurs through phosphorylation at ser-473 or ser-474, respectively. Pdk1 phosphorylates akt-2 at thr 309 in the catalytic domain, leading to enzymatic activation.
SIGNOR-134485
Q07955
P49761
0
phosphorylation
up-regulates activity
0.531
In vitro, Clk/Sty efficiently phosphorylated the SR family member ASF/SF2 on serine residues located within its serine/arginine-rich region (the RS domain). Overexpression of the active Clk/Sty kinase caused a redistribution of SR proteins within the nucleus. These results suggest that Clk/Sty kinase directly regulates the activity and compartmentalization of SR splicing factors.
SIGNOR-273859
P78527
P67809
1
phosphorylation
up-regulates activity
0.338
The DNA-PK subunits and YB-1 phosphorylated at T89 were found colocalized suggesting their in vivo interaction.DNA-PK directly phosphorylates YB-1 and, this way, modulates YB-1 function. Point mutation of YB-1 at this residue abrogated the translocation of YB-1 into the nucleus.
SIGNOR-277611
Q13131
P52292
1
phosphorylation
up-regulates
0.2
Ampk phosphorylated importin alpha1 on ser(105). Accordingly, expression of importin alpha1 proteins bearing k22r or s105a mutations failed to mediate the nuclear import of hur in intact cells. Our results point to importin alpha1 as a critical downstream target of ampk and key mediator of ampk-triggered hur nuclear import.
SIGNOR-128629
Q13464
O43293
1
phosphorylation
up-regulates activity
0.306
ROCK1 phosphorylates and activates ZIPK suggesting that at least some of these physiological functions may require both enzymes.
SIGNOR-279102
Q13546
Q13489
0
polyubiquitination
up-regulates activity
0.747
CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.
SIGNOR-272713
Q99500
Q14344
2
binding
up-regulates
0.529
Edg-3 and edg-5 couple not only to gibut also to gqand g13.
SIGNOR-70710
Q9UHV7
Q969H0
0
ubiquitination
down-regulates quantity by destabilization
0.371
The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator. We show that Fbw7, a tumor suppressor and ubiquitin ligase, binds to CDK8-Mediator and targets MED13/13L for degradation. MED13/13L physically link the CDK8 module to Mediator, and Fbw7 loss increases CDK8 module-Mediator association.
SIGNOR-266690
P42574
Q9UKV3
1
cleavage
up-regulates
0.628
Induces apoptotic chromatin condensation after activation by casp3
SIGNOR-70800
P24941
P10244
1
phosphorylation
up-regulates activity
0.718
Ten phosphorylation sites carboxyl-terminal to the DNA-binding domain were identified by this method: threonines at positions 267, 408, 497, 519, 522, and 524 and serines at positions 283, 396, 455, and 581. | Our results indicate that B-Myb can be phosphorylated in a cell-free system by both cyclin A-Cdk2 and cyclin E-Cdk2 complexes. | These data suggest that B-Myb is a target for phosphorylation by cyclin-Cdk2 and that phosphorylation of B-Myb regulates its transcriptional activity.
SIGNOR-250735
P06493
P30305
2
phosphorylation
up-regulates
0.829
Ser(321) is phosphorylated in mitosis by cdk1. The mitotic phosphorylation of ser(321) acts to maintain full activation of cdc25b by disrupting 14-3-3 binding to ser(323) and enhancing the dephosphorylation of ser(323) to block 14-3-3 binding to this site.
SIGNOR-167641
Q9H6I2
P35222
2
binding
down-regulates
0.686
Two additional sox proteins, xsox17alfa and xsox3 , likewise bind to beta-catenin and inhibit its tcf-mediated signaling activity
SIGNOR-72006
Q05655
P35236
1
phosphorylation
up-regulates activity
0.2
HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. ​(Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.
SIGNOR-276048
P49768
Q00535
0
phosphorylation
up-regulates
0.51
Cyclin-dependent kinase-5/p35 phosphorylates presenilin 1 to regulate carboxy-terminal fragment stabilityhere we demonstrate that cyclin dependent kinase-5/p35 (cdk5/p35) phosphorylates ps1 on threonine(354) within c-ps1 both in vitro and in vivo. Threonine(354) phosphorylation functions to selectively stabilize c-ps1.
SIGNOR-89145
Q9UKI8
P68431
1
phosphorylation
up-regulates activity
0.2
Purified tlk1b phosphorylated histone h3 at s(10) with high specificity both in a mix of core histones and in isolated chromatin, suggesting that histone h3 is a physiological substrate for tlk1b. Phosphorylation of H3 has been linked to the activation of the immediate-early genes upon mitogenic stimulation, and to chromatin condensation during mitotic/meiotic events.
SIGNOR-107037
Q99638
O14757
0
phosphorylation
up-regulates activity
0.669
Chk1 inhibition with small interfering RNA (siRNA) reduces Rad9A stabilization and accumulation.|In the case of DNA damage, an activated Chk1 phosphorylates Rad9A or other proteins (TLK1) as a feedback mechanism to prevent Rad9A (poly) ubiquitination and degradation.
SIGNOR-279503
P45983
Q12968
1
phosphorylation
down-regulates
0.837
Jnks directly phosphorylate nuclear factor of activated t-cell (nfat) transcription factors, thus antagonizing the effects of calcium-regulated signaling through the protein phosphatase calcineurin
SIGNOR-118220
Q6ZN17
Q2Q1W2
0
polyubiquitination
down-regulates quantity by destabilization
0.527
In cells, TRIM71 negatively regulates Lin28B protein stability by catalyzing polyubiquitination. 
SIGNOR-272054
O94813
P35052
2
binding
up-regulates
0.604
Slit family proteins are functional ligands of glypican-1 in nervous tissue and suggest that their interactions may be critical for certain stages of central nervous system histogenesis.
SIGNOR-68428
P48729
O60716
1
phosphorylation
up-regulates activity
0.2
Moreover, CK1α phosphorylates p120-catenin on Ser268 and Ser269, releasing this protein from the signalosome and facilitating the subsequent phosphorylation of cadherin and the disruption of this cadherin interaction with LRP5/6
SIGNOR-277893
O14649
Q13464
0
phosphorylation
down-regulates
0.2
Task1 channels contain two putative rho kinase phosphorylation sites, ser(336) and ser(393) . Mutation of ser(393) rendered task1 channels insensitive to et(a) - or et(b)-mediated current inhibition. In contrast, removal of ser(336) selectively attenuated et(a) -dependent task1 regulation without affecting the et(b) pathway.
SIGNOR-176025
Q12959
P24941
0
phosphorylation
up-regulates
0.282
We also show that dlg1 is phosphorylated by both cdk1 and cdk2 on ser158 and ser442. These phosphorylated sites together affect the nuclear localisation of the protein, and implicate the role of phosphorylation on ser158 and ser442 in its putative nuclear functions as a tumour suppressor. phosphorylation on ser158 and ser442 enhances nuclear expression of dlg1
SIGNOR-182765
Q9P286
O95831
1
phosphorylation
down-regulates activity
0.2
Our results show that PAK5 can phosphorylate Thr-281 of AIF, which is included in its NLS1 sequence.|These results suggested that PAK5 inhibited AIF from entering the nucleus through phosphorylation of AIF T281 site, thus inhibiting cell apoptosis.
SIGNOR-279085
P60981
Q96S53
0
phosphorylation
down-regulates activity
0.422
The present study provides evidence that TESK2 can phosphorylate cofilin and ADF specifically at Ser-3. Since actin-depolymerizing and -severing activities of cofilin/ADF are abrogated by phosphorylation at Ser-3, TESK2 seems to play an important role in actin filament dynamics by inhibiting cofilin/ADF activity.
SIGNOR-246707
Q7KZI7
Q8IVT5
1
phosphorylation
down-regulates activity
0.315
In vivo, MARK2 appears to negatively regulate KSR1 in insulin sensitivity.|These data suggest that MARK2 phosphorylates KSR1 on Ser392, which has been shown previously to function as a negative regulatory site xref .
SIGNOR-279343
Q15759
P15336
1
phosphorylation
up-regulates
0.756
Our results indicate that atf-2 not only directly binds to smad3/4 hetero-oligomers but also that atf-2 is phosphorylated by tgf-beta signaling via tak1 and p38. The two pathways, smad and tak1, synergistically enhance the activity of atf-2 which acts as their common nuclear target
SIGNOR-65586
O14920
P42771
1
phosphorylation
down-regulates
0.396
Ikkbeta specifically binds to p16 and phosphorylates ser8 of p16 phosphorylation at ser8 of p16 brings about a significant loss of its cyclin-dependent kinase (cdk) 4-inhibitory activity
SIGNOR-163801
P49593
Q9UQM7
1
dephosphorylation
down-regulates
0.331
Ppm1f specifically dephosphorylates the phospho-thr-286 in autophosphorylated camkii substrate and thus deactivates the camkii in vitro.
SIGNOR-124309
P16949
O15264
0
phosphorylation
down-regulates
0.414
Serine 25 of oncoprotein 18 is a major cytosolic target for the mitogen-activated protein kinase.
SIGNOR-36362
P48730
Q00535
1
phosphorylation
up-regulates activity
0.555
We also show that casein kinase I, but not casein kinase II, can phosphorylate and activate cdk5 in vitro.
SIGNOR-250798
Q9H2K8
Q13043
1
phosphorylation
up-regulates
0.283
In addition, the thousand-and-one (tao) amino acids kinase or taok13 has been shown to directly phosphorylate and activate hpo or mst1/2
SIGNOR-192762
P02686
P27361
0
phosphorylation
down-regulates
0.502
Phosphorylation decreased the ability of mbp to polymerize actin and to bundle actin filaments but had no effect on the dissociation constant of the mbp-actin complex or on the ability of ca2+-calmodulin to dissociate the complex. The most significant effect of phosphorylation on the mbp-actin complex was a dramatic reduction in its ability to bind to negatively charged lipid bilayers. The identification of myelin basic protein (phosphorylation at -pro-arg-thr-pro-) as a substrate for the erk kinases (fig. 1) demonstrates that there are other determinants important for substrate recognition than those present in the originally identified consensus sequence.
SIGNOR-143481
P50148
Q03431
2
binding
up-regulates activity
0.275
This calciotropic hormone exerts its actions via binding to the PTH/PTH-related peptide receptor (PTH1R), which couples to multiple heterotrimeric G proteins, including Gs and Gq/11.
SIGNOR-270550
P0DP24
P29474
2
binding
up-regulates activity
0.505
Electrons flow from the C-terminal reductase domain of one NOS monomer to the N-terminal oxygenase domain of the other NOS monomer (Siddhanta et al., 1998). The primary mode of enzyme activation is the binding of calcium-bound calmodulin to the N-terminal CaM-binding domain. This facilitates a structure change and the flow of electrons from NADPH through the flavins to the oxygenase domain of the other eNOS monomer
SIGNOR-266323
P19838
Q04206
2
binding
up-regulates activity
0.713
Here we report the crystal structure at 2.9 a resolution of the p50/p65 heterodimer bound to the kappab dna
SIGNOR-55378
P63104
P49137
0
phosphorylation
down-regulates activity
0.625
We confirmed that MAPKAPK2 interacted with and phosphorylated 14-3-3zeta in vitro and in HEK293 cells. Mutation analysis showed that MAPKAPK2 phosphorylated 14-3-3zeta at Ser-58. S58D mutation significantly impaired both 14-3-3zeta dimerization and binding to Raf-1.
SIGNOR-250151
Q9Y4C1
Q71DI3
1
demethylation
up-regulates activity
0.2
Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. 
SIGNOR-276844
Q14694
P04637
1
deubiquitination
up-regulates quantity by stabilization
0.662
Since USP10 is known as a deubiquitinating protease of p53 (Yuan et al., 2010), inhibition of USP10 by spautin-1 may promote the degradation of p53. 
SIGNOR-260297
P15056
P01112
2
binding
up-regulates activity
0.878
The raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases.
SIGNOR-147327
Q15797
P23771
1
transcriptional regulation
up-regulates quantity
0.291
Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation
SIGNOR-268938
O14641
Q13467
2
binding
up-regulates activity
0.704
Upon ligand binding, DVL proteins are recruited to Frizzled receptors at the plasma membrane and co-recruit cytoplasmic transducers, such as Axin, CK1 and GSK3 binding protein (GBP), presumably along with their partners, to promote ?-catenin-dependent signalling. 
SIGNOR-258960
Q76L83
P37231
2
binding
up-regulates activity
0.2
ASXL2, which does not bind HP1, promotes differentiation by binding to PPARγ and increasing the level of methylated H3K4, leading to the elevation of PPARγ activity. Our genome-wide analysis confirmed the physiological roles of ASXL1 and ASXL2 in adipogenesis at the molecular level, supporting the hypothesis that ASXL1 is an authentic corepressor of PPARγ, whereas ASXL2 is a PPARγ coactivator, and that together ASXL1 and ASXL2 fine-tune adipogenesis via differential regulation of PPARγ.
SIGNOR-260063
Q15797
O14595
0
dephosphorylation
down-regulates
0.5
In human cells, rnai-mediated depletion of scp1 and scp2 increases the extent and duration of smad1 phosphorylation in response to bmp, the transcriptional action of smad1, and the strength of endogenous bmp gene responses. The present identification of the scp family as smad c-terminal phosphatases sheds light on the events that attenuate smad signaling and reveals unexpected links to the essential phosphatases that control rna polymerase ii in eukaryotes.
SIGNOR-148434
P31749
P46937
1
phosphorylation
down-regulates
0.593
One protein that associates with 14-3-3 in an akt-dependent manner is shown here to be the yes-associated protein (yap), which is phosphorylated by akt at serine 127, leading to binding to 14-3-3. Akt promotes yap localization to the cytoplasm, resulting in loss from the nucleus where it functions as a coactivator of transcription factors including p73.
SIGNOR-252593
Q96BR1
Q9Y2I7
1
phosphorylation
up-regulates activity
0.461
The Western blot in XREF_FIG demonstrates that SGK3 as well as PKB phosphorylate PIKfyve at position S318, thereby indicating that PIKfyve could be a physiological target of SGK3.|We here identify a novel mechanism involving NMDA receptor triggered, SGK3 dependent stimulation of PIKfyve with subsequent formation of PI (3,5) P 2, which modulates RAB11A facilitated vesicle transport to the plasma membrane, leading to an increased abundance of GluA1 receptor subunits in the plasma membrane.
SIGNOR-279113
P49841
O15033
1
phosphorylation
down-regulates quantity by destabilization
0.316
These experiments suggested that GSK3beta phosphorylation of FIEL1 is required for PIAS4 targeting, and FIEL1 residues P779 and phosphorylated T783 are both required for PIAS4 interaction |FIEL1 T783A mutant overexpression completely failed to decrease PIAS4 protein level.
SIGNOR-275528
Q13541
Q9P1W9
0
phosphorylation
up-regulates activity
0.414
Further, PIM2 triggered phosphorylation of AKT and 4EBP1 (XREF_FIG) clearly demonstrating the activation of PI3K pathway.
SIGNOR-279091
P04406
O14867
0
transcriptional regulation
up-regulates quantity
0.2
BACH1 activates transcription of Hexokinase 2 and Gapdh and increases glucose uptake, glycolysis rates, and lactate secretion, thereby stimulating glycolysis-dependent metastasis of mouse and human lung cancer cells.
SIGNOR-259339
Q92585
Q04721
2
binding
up-regulates
0.808
Maml1 binds to the ankyrin repeat domain of all four mammalian notch receptors, forms a dna-binding complex with icn and rbp-jkappa, and amplifies notch-induced transcription of hes1.
SIGNOR-84835
Q5JVS0
Q06413
2
binding
down-regulates activity
0.338
MEF2C DNA-binding activity is inhibited through its interaction with the regulatory protein Ki-1/57.
SIGNOR-238283
P46937
P06493
0
phosphorylation
up-regulates activity
0.425
Our evidence suggested that these YAP sites (Ser138, Thr143, and Ser367) were CDK1 phosphorylation sites.|These data demonstrate that the YAP phosphorylation sites Ser138, Thr143, and Ser367 are important for proper mitosis and cytokinesis.
SIGNOR-276587
P06401
P24941
0
phosphorylation
down-regulates
0.441
Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26s proteasome
SIGNOR-74708
P59594
P07711
0
cleavage
up-regulates activity
0.2
A cell-free membrane-fusion system demonstrates that engagement of receptor followed by proteolysis is required for SARS-CoV membrane fusion and indicates that cathepsin L is sufficient to activate membrane fusion by SARS-CoV S. These results suggest that SARS-CoV infection results from a unique, three-step process: receptor binding and induced conformational changes in S glycoprotein followed by cathepsin L proteolysis within endosomes. The requirement for cathepsin L proteolysis identifies a previously uncharacterized class of inhibitor for SARS-CoV infection.
SIGNOR-260218
P17612
Q9UNF0
1
phosphorylation
down-regulates activity
0.2
PKCα phosphorylates PACSIN2 at serine 313 in the linker region and decreases its membrane binding and tubulation activities. Phosphorylation of PACSIN2 at S313 negatively regulated protein interaction between NS5A and core, which affected viral assembly
SIGNOR-273799
Q5SQI0
Q9BQE3
1
acetylation
up-regulates quantity by stabilization
0.246
Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules
SIGNOR-272247