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P63096
P43657
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-256725
Q9UGJ0
Q13586
1
phosphorylation
down-regulates activity
0.2
STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE
SIGNOR-277297
Q14457
P19484
0
transcriptional regulation
up-regulates quantity by expression
0.409
As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;
SIGNOR-276558
P47211
P63096
2
binding
up-regulates activity
0.472
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-256687
Q9HAZ1
Q07955
1
phosphorylation
up-regulates activity
0.357
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-273860
O00330
Q99626
2
binding
down-regulates activity
0.2
In the heterologous cell line BHK-21, Pdx1 inhibited by 60 to 80% the activation of the alpha-cell specific element G1 conferred by Pax-6 and/or Cdx-2/3. Although Pdx1 could bind three AT-rich motifs within G1, two of which are binding sites for Pax-6 and Cdx-2/3, the affinity of Pdx1 for G1 was much lower as compared to Pax-6. In addition, Pdx1 inhibited Pax-6 mediated activation through G3, to which Pdx1 was unable to bind. Moreover, a mutation impairing DNA binding of Pdx1 had no effect on its inhibition on Cdx-2/3. Since Pdx1 interacts directly with Pax-6 and Cdx-2/3 forming heterodimers, we suggest that Pdx1 inhibits glucagon gene transcription through protein to protein interactions with Pax-6 and Cdx-2/3.
SIGNOR-254904
Q00535
Q05655
0
phosphorylation
down-regulates activity
0.2
This generates a binding site for the C2 domain of PKCδ, which in turn phosphorylates CDK5 on T77. The resulting dissociation of the CDK5R1/CDK5 complex abolishes the activity of CDK5. 
SIGNOR-277386
P05112
P78552
2
binding
up-regulates
0.782
It is now known that this alternate receptor is a heterodimer, the type ii il-4 receptor or the il-13 receptor, which is comprised of IL-4R And IL-13R1.
SIGNOR-100759
O43156
Q9UK97
2
binding
down-regulates quantity by destabilization
0.467
Here we report that Tel2 and Tti1 are targeted for degradation within mTORC1 by the SCFFbxo9 ubiquitin ligase to adjust mTOR signalling to growth factor availability. The interaction between Tel2/Tti1 and Fbxo9 identified by mass spectrometry suggests that SCFFbxo9 is probably the ubiquitin ligase that mediates degradation of both proteins.
SIGNOR-271997
Q92956
O43557
2
binding
up-regulates
0.857
A member of the tumor necrosis factor (tnf) superfamily, human tnfsf14 (htnfsf14)/hvem-l (herpes virus entry mediator ligand) was isolated as a cellular ligand for hvem/tr2 and human lymphotoxin beta receptor (ltbetar). Tnfsf14 induces apoptosis and suppresses tumor formation
SIGNOR-79328
P49674
Q13541
1
phosphorylation
down-regulates
0.2
Mechanistic investigations showed that ck1_ interacted with and phosphorylated 4e-bp1 at two novel sites t41 and t50, which were essential for 4e-bp1 inactivation along with increased mrna translation and cell proliferation.
SIGNOR-203240
P42224
Q07912
0
phosphorylation
up-regulates activity
0.357
Hence, ACK1 activates STAT1 through its kinase activity.|We found that wild-type ACK1 and to a larger extent constitutively active ACK1 increased the phosphorylation of cytoplasmic STAT1 at Y701.
SIGNOR-278348
Q2T9J0
Q86WA8
0
cleavage
down-regulates quantity by destabilization
0.66
Self-cleavage of Tysnd1 in the active oligomer most likely inactivates its protease activity. Subsequently, the cleaved products are degraded by PsLon and removed from the Tysnd1 oligomer.
SIGNOR-261054
P49841
P30281
1
phosphorylation
down-regulates
0.435
We have previously shown that both basal and camp-induced degradation of cyclin d3 in reh cells is dependent on thr-283 phosphorylation by glycogen synthase kinase-3beta (gsk-3beta).
SIGNOR-142880
P08754
Q969V1
2
binding
up-regulates activity
0.435
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-257180
Q99704
P06213
0
phosphorylation
up-regulates activity
0.562
Insulin receptor-mediated p62dok tyrosine phosphorylation at residues 362 and 398. p62(dok) is a direct substrate for the IR tyrosine kinase and that phosphorylation at Tyr(362) and Tyr(398) plays an essential role for p62(dok) to interact with its effectors and negatively regulate the insulin signaling pathway.
SIGNOR-251307
Q6IQ55
O00139
1
phosphorylation
down-regulates activity
0.406
TTBK2 phosphorylates KIF2A primarily at growing MT ends and counteracts the depolymerization activity of KIF2A
SIGNOR-260926
O76094
P09132
2
binding
up-regulates activity
0.942
Mammalian SRP comprises the highly base-paired SRP RNA (also referred to as 7SL RNA) of ∼300 nt and six proteins (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) (Figure ​(Figure1A).1A). The hierarchy of protein addition always starts with the scaffolding protein SRP19 (together with SRP9/14 for the entire SRP) followed by SRP68/72 and finally by SRP54.
SIGNOR-261166
Q9NPG1
P41221
2
binding
up-regulates activity
0.707
Human wnt5a, wnt5b and wnt11 are non-canonical wnt ligands transducing pcp signals through fzd3 or fzd6 receptors.
SIGNOR-141434
P43115
Q9UBI6
2
binding
up-regulates
0.45
Ep3 receptor signals are primarily involved in adenylyl cyclase via g(i) activation, and in ca(2+)-mobilization through g(beta)(gamma) from g(i)
SIGNOR-88195
P16284
P16591
0
phosphorylation
up-regulates activity
0.322
PECAM-1 Is Phosphorylated by Fer and, To a Lesser Extent, by Fes. These results suggest that Fer not only functions as a tyrosine kinase for PECAM-1 but also that Fer modulates the downstream signaling of PECAM-1 by inducing phosphorylation of SHP-2 and Gab1.
SIGNOR-262866
P05412
Q00526
0
phosphorylation
up-regulates
0.443
Egf-induced cdk3 activation caused c-jun phosphorylation at ser63 and ser73, resulting in increased ap-1 transactivation.
SIGNOR-183013
Q9UPT6
O14733
2
binding
up-regulates
0.7
These data demonstrate that jip3 interacts with proteins that can form a mapk signaling module, including jnk, mkk7, and mlk3
SIGNOR-73906
P53611
P24386
2
binding
down-regulates activity
0.768
Prenylation (or geranylgeranylation) of Rab GTPases is catalysed by RGGT (Rab geranylgeranyl transferase) and requires REP (Rab escort protein). In the classical pathway, REP associates first with unprenylated Rab, which is then prenylated by RGGT. In the alternative pathway, REP associates first with RGGT; this complex then binds and prenylates Rab proteins.
SIGNOR-265571
Q15797
P27361
0
phosphorylation
down-regulates
0.528
Ras signaling was shown previously to induce the phosphorylation of the bmp mediator smad1 at four erk consensus sites in the linker domain (kretzschmar et al. 1997a). Phosphorylation of these four sites inhibits smad1 accumulation in the nucleus
SIGNOR-66755
Q16695
O75151
0
demethylation
down-regulates activity
0.2
PHF2, a jmjC demethylase, is enzymatically inactive by itself, but becomes an active H3K9Me2 demethylase through PKA-mediated phosphorylation. This modification leads to targeting of the PHF2–ARID5B complex to its target promoters, where it removes the repressive H3K9Me2 mark.
SIGNOR-264520
P56915
O00308
0
ubiquitination
up-regulates activity
0.31
These results indicated that Wwp2 augments the transcription activity of Gsc.|We confirmed that Gsc was being mono-ubiquitinated by Wwp2 via in vitro ubiquitination assays that utilized purified Gsc, recombinant Wwp2 and ubiquitin-K0 proteins that resulted in a pattern of Gsc ubiquitination similar to WT ubiquitin (XREF_FIG).
SIGNOR-278797
P36969
Q16236
0
transcriptional regulation
up-regulates quantity by expression
0.383
NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.GPX4 stands out within the GPX family due to its unique ability to reduce lipid hydroperoxides directly within cell membranes, thereby safeguarding cells from lipid peroxidation and ferroptosis.
SIGNOR-279874
P28482
P49585
1
phosphorylation
down-regulates
0.45
Oxysterols inhibit phosphatidylcholine synthesis via erk docking and phosphorylation of ctp:phosphocholine cytidylyltransferase. Mutagenesis of ser315 within cctalpha was both required and sufficient to confer significant resistance to 22-hc/9-cis-ra inhibition of ptdcho synthesis.
SIGNOR-134837
P53350
O60260
1
phosphorylation
up-regulates activity
0.2
 Parkin Is Phosphorylated by Plk1 at Ser378 and Activated during Mitosis 
SIGNOR-276938
P08476
P27037
2
binding
up-regulates activity
0.815
A protein of 494 amino acids comprising a ligand-binding extracellular domain, a single membrane-spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. 125I-activin A binds to transfected COS cells with an affinity of 180 pM and can be competed by activin A, activin B, and inhibin A, but not by transforming growth factor beta 1.
SIGNOR-235138
P78344
P06493
0
phosphorylation
up-regulates activity
0.339
To test whether CDK1 phosphorylates T508, Flag-DAP5 was purified from dox-induced HEK293 cells and incubated with active recombinant JNK2 or CDK1 in the presence of ATP (Fig. 3G). DAP5(T508) was phosphorylated only upon incubation with CDK1 (Fig. 3G).
SIGNOR-266387
Q03113
Q9NPG1
2
binding
up-regulates
0.244
Gpcrs signal through four relatively small families of galfa proteins (galfas, galfai/o, galfaq, and galfa12/13), and if fzd receptors are classic gpcrs, they should signal through one of these four galfa families.
SIGNOR-122889
O00555
Q01484
2
binding
up-regulates quantity
0.263
Here, we demonstrate that ankyrin-B associates with Cav2.1 and Cav2.2 in cortex, cerebellum, and brain stem. Additionally, using in vitro and in vivo techniques, we demonstrate that ankyrin-B, via its membrane-binding domain, associates with a highly conserved motif in the DII/III loop domain of Cav2.1 and Cav2.2. Collectively, our findings identify an interaction between ankyrin-B and both Cav2.1 and Cav2.2 at the amino acid level that is necessary for proper Cav2.1 and Cav2.2 targeting in vivo.
SIGNOR-266706
O43524
Q96EB6
0
deacetylation
up-regulates activity
0.911
Sirt1 increased foxo3's ability to induce cell cycle arrest and resistance to oxidative stress
SIGNOR-122405
Q9P278
P08238
2
binding
down-regulates activity
0.263
FNIP1 and FNIP2 facilitate FLCN binding to Hsp90 chaperone. Our results suggest that FNIP1 is a potent inhibitor of Hsp90 ATPase activity, as 200 nM of FNIP1 inhibits Hsp90 ATPase activity by 50-fold. FNIP2 also has shown inhibitory activity towards Hsp90; however, it required 1.6 μM of FNIP2 to inhibit the ATPase activity by eightfold. Although we use the term ‘inhibition' here, FNIPs seem only to be slowing the chaperone cycle.
SIGNOR-261416
Q9BUB5
P27361
0
phosphorylation
up-regulates
0.576
Mnk1 was phosphorylated and activated in vitro by erk1 and p38 map kinasespreliminary results showed that thr344 at least was one of the major sites phosphorylated by erk1
SIGNOR-48360
Q9UD71
P36873
2
binding
down-regulates activity
0.591
DARPP-32 (dopamine and cyclic AMP-regulated phospho-protein, relative molecular mass 32,000) is converted into an inhibitor of protein phosphatase 1 when it is phosphorylated by protein kinase A (PKA) at threonine 34.‚ 
SIGNOR-264958
Q13976
P35367
1
phosphorylation
down-regulates
0.2
Ser396 and ser398 are also potential phosphorylation sites for capk, cgmp-dependent protein kinase, and camk ii. Elevation of intracellular camp content has been shown to attenuate histamine-induced accumulation of ip in c6 glioma cells (peakman and hill, 1994) and in ddt1 mf-2 smooth muscle cells (sipma et al., 1995
SIGNOR-66019
O15169
O75197
0
relocalization
down-regulates quantity
0.83
Axin is a protein that interacts with the intracellular domain of LRP-5. LRP-5 active form bind Axin and induce LEF-1 activation by destabilizing Axin and stabilizing beta-catenin.
SIGNOR-236997
Q9UIF8
P68431
2
binding
down-regulates activity
0.2
The BAZ2B bromodomain has been shown to bind to acetylated H3K14 (H3K14ac), whose presence at promoter regions is generally associated with gene activation. This suggests a potential role for BAZ2B in transcriptional activation.
SIGNOR-266622
P20333
Q9HAU4
0
ubiquitination
up-regulates activity
0.326
However, co-transfection of Smurf2, but not Smurf2-C/A, drastically increased the potential of TNF-R2 to induce JNK phosphorylation.|In conclusion, these results indicate that Smurf2 is able to ubiquitinate TNF-R2, which is further enhanced by the TRAF2-mediated targeting of Smurf2 to TNF-R2.
SIGNOR-278716
P53779
P05067
1
phosphorylation
up-regulates
0.582
Phosphorylation of amyloid precursor protein at threonine 668 is essential for its copper-responsive trafficking in sh-sy5y neuroblastoma cells. is regulated by jnk3 via phosphorylation of app at thr668
SIGNOR-204671
P31749
Q13188
1
phosphorylation
down-regulates
0.356
We determined that mst2 phosphorylation by akt limits mst2 activity in two ways: first, by blocking its binding to rassf1a and by promoting its association into the raf-1 inhibitory complex, and second, by preventing homodimerization of mst2, which is needed for its activation. we identified t117 and t384 as akt phosphorylation sites in mst2.
SIGNOR-163533
P45985
P19793
1
phosphorylation
down-regulates
0.2
Phosphorylation by mkk4/sek1 had profound effects on the biochemical properties of rxr, inhibiting the expression of genes activated by rxr-retinoic acid receptor complexes. Tyr-249 in the rxr de region was required for the inhibitory effect of mkk4/sek1.
SIGNOR-80619
Q14653
P78527
0
phosphorylation
up-regulates
0.43
Phosphorylation of irf-3 by dna-pk after virus infection results in its nuclear retention and delayed proteolysis
SIGNOR-115331
P48730
Q2M2I3
2
binding
up-regulates quantity
0.2
We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.
SIGNOR-273767
Q9BRS8
Q08211
2
binding
up-regulates activity
0.41
 La ribonucleoprotein domain family member 6 (LARP6) is the protein that binds 5' SL with high affinity and specificity and coordinates their translation. Here we show that RNA helicase A (RHA) is tethered to the 5' SL of collagen mRNAs by interaction with the C-terminal domain of LARP6. 
SIGNOR-273500
P55061
Q9NZS9
0
polyubiquitination
down-regulates quantity by destabilization
0.392
BAR overexpression promotes BI-1 ubiquitination and proteasomal degradation.We show here that bifunctional apoptosis regulator (BAR) functions as an ER-associated RING-type E3 ligase, interacts with BI-1, and promotes proteasomal degradation of BI-1. 
SIGNOR-272778
Q92973
P49792
2
binding
up-regulates activity
0.455
Nup358(806–1306), but not other regions, efficiently recruits importin β and transportin 1
SIGNOR-262111
P42356
Q14156
2
binding
up-regulates quantity
0.47
PI4KA is recruited to plasma membrane by the adapter protein EFR3, which has two isoforms, EFR3A and EFR3B
SIGNOR-269092
O75787
P00797
2
binding
up-regulates
0.787
We report the expression cloning of the human renin receptor complementary dna encoding a 350-amino acid protein with a single transmembrane domain and no homology with any known membrane protein. Transfected cells stably expressing the receptor showed renin- and prorenin-specific binding. The binding of renin induced a fourfold increase of the catalytic efficiency of angiotensinogen conversion to angiotensin i and induced an intracellular signal with phosphorylation of serine and tyrosine residues associated to an activation of map kinases erk1 and erk2
SIGNOR-88416
Q9HBW0
P50148
2
binding
up-regulates activity
0.597
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-257382
P30550
P09471
2
binding
up-regulates activity
0.268
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-257247
Q96RL1
P54132
2
binding
up-regulates activity
0.329
Here, we demonstrate that the ubiquitin/SUMO-dependent DNA damage response (UbS-DDR), controlled by the E3 ligases RNF8/RNF168, triggers BLM recruitment to sites of replication fork stalling via ubiquitylation in the N-terminal region of BLM and subsequent BLM binding to the ubiquitin-interacting motifs of . 
SIGNOR-272116
O94874
Q13315
2
ubiquitination
up-regulates activity
0.2
UFM1 specific ligase 1 (UFL1), an ufmylation E3 ligase, is important for ATM activation. UFL1 is recruited to double strand breaks by the MRE11/RAD50/NBS1 complex, and monoufmylates histone H4 following DNA damage.
SIGNOR-265073
Q93045
P17612
0
phosphorylation
down-regulates activity
0.309
Using in vitro phosphorylated recombinant protein, four phosphorylation sites were identified in the SCG10 sequence. Ser-50 and Ser-97 were the target sites for protein kinase A. phosphorylation negatively regulates the microtubule-depolymerizing activity of SCG10 and that all four sites participate in this regulation
SIGNOR-250056
P12830
O14770
0
transcriptional regulation
up-regulates quantity by expression
0.2
We show that the Pbx1 and Meis2 homeodomain proteins interact with Klf4 and can be recruited to DNA elements comprising a Klf4 site or G C box, with adjacent Meis and Pbx sites. Meis2d and Pbx1a activate expression of p15(Ink4a) and E-cadherin, dependent on the Meis2d transcriptional activation domain. We suggest a model in which genes with Klf4 sites can be cooperatively activated by Meis2/Pbx1 and Klf4, dependent primarily on recruitment by Klf4.
SIGNOR-267242
Q6A1A2
P31749
1
phosphorylation
up-regulates
0.2
Akt to the plasma membrane where it is phosphorylated and activated by phosphoinositide-dependent kinase (pdk) 1 and pdk2.
SIGNOR-252628
P20827
P29322
2
binding
up-regulates
0.817
Ephrins are cell-surface tethered guidance cues that bind to eph receptor tyrosine kinases in trans on opposing cells.
SIGNOR-154298
P43405
Q32MZ4
1
phosphorylation
up-regulates activity
0.2
However, this inhibitory activity TRIP can be reversed by the co-expression of Syk, which might inhibit the activity of cytoplasmic TRIP, sequester TRIP from important nucleolar targets or even counter TRIP 's inhibitory effects on TRAF and TNF signaling by regulating the activity of alternative components of the pathway.|Syk induces phosphorylation of TRIP on tyrosine.
SIGNOR-279297
Q6JBY9
P49137
0
phosphorylation
down-regulates activity
0.477
Human CapZIP was phosphorylated at Ser-179 and Ser-244 by MAPKAP-K2 (mitogen-activated protein kinase-activated protein kinase 2) or MAPKAP-K3 in vitro. In the present paper we have identified CapZIP as a protein that is phosphorylated exceptionally rapidly by several SAPKs in vitro (Figure 4), and which is expressed in muscles and immune cells. Both MAPKAP-K2 and MAPKAP-K3 phosphorylated CapZIP at Ser-179 in vitro. An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.
SIGNOR-263080
Q86WV6
Q9BY78
0
ubiquitination
up-regulates activity
0.2
As a result, knockdown of RNF26 promoted degradation of MITA after viral infection and prevented degradation of IRF3.|In addition, RNF26 could not induce polyubiquitination of MITA (K150R) in in vitro ubiquitination assays (XREF_FIG).
SIGNOR-278573
O60885
P01106
2
phosphorylation
down-regulates quantity by destabilization
0.562
We report that BRD4 phosphorylates MYC at Thr58, leading to MYC ubiquitination and degradation, thereby regulating MYC target genes.
SIGNOR-262046
P31314
P14921
2
binding
down-regulates activity
0.467
We show that the cortical thymic maturation arrest in T-lineage ALLs that overexpress TLX1 or TLX3 is due to binding of TLX1/TLX3 to ETS1, leading to repression of T cell receptor (TCR) α enhanceosome activity and blocked TCR-Jα rearrangement.
SIGNOR-259097
P17252
P19429
1
phosphorylation
up-regulates activity
0.343
In addition to the established phosphorylation sites (S22 and S23) we found that S38 and S165 were the other two main sites of phosphorylation. | Phosphorylation of S22/23A also decreased its affinity for troponin C indicating that phosphorylation of S38 and/or S165 impedes binding of troponin I to troponin C. Formation of a troponin I/troponin C complex prior to cAMP-dependent protein kinase treatment did not prevent overphosphorylation.
SIGNOR-249066
P06493
P19525
0
phosphorylation
down-regulates
0.328
Our findings demonstrate that (i) pkr, ser/thr kinase, phosphorylates its new substrate cdc2 at the tyr 4 residue, (ii) pkr-mediated tyr 4-phosphorylation facilitates cdc2 ubiquitination and proteosomal degradation
SIGNOR-164809
P19484
P28482
0
phosphorylation
down-regulates activity
0.413
Evidence for ERK2-mediated TFEB phosphorylation came from ERK2-TFEB coimmuno-precipitation (fig. S12C) in normal but not in starved medium and from a peptide-based kinase assay showing that mutation of Ser142 to alanine abolished ERK2-mediated phosphorylation (
SIGNOR-248279
P68400
P18848
1
phosphorylation
down-regulates quantity by destabilization
0.2
By using mutants of ATF4 we identified serine 215 as the main CK2 phosphorylation site. The ATF4 S215A mutant turned out to be more stable than the wild-type form. 
SIGNOR-276425
P21333
Q8WUP2
2
binding
up-regulates activity
0.888
Kindlin binds migfilin tandem LIM domains and regulates migfilin focal adhesion localization and recruitment dynamics. Two integrin-binding proteins present in FAs, kindlin-1 and kindlin-2, are important for integrin activation, FA formation, and signaling. By binding filamin, migfilin provides a link between kindlin and the actin cytoskeleton.
SIGNOR-266105
P19419
Q16539
0
phosphorylation
up-regulates
0.526
We demonstrate here that elk-1 is barely activated by a third subclass of map kinases (p38), most likely because the critical residues ser383 and ser389 are poorly phosphorylated by p38 map kinase.
SIGNOR-47630
Q9UNH5
Q96R06
1
dephosphorylation
down-regulates activity
0.2
We also demonstrate that Cdc14A dephosphorylates Astrin, and therefore the overexpression of Cdc14A sequesters Astrin in the centrosome and results in aberrant chromosome alignment.
SIGNOR-277066
P53350
P37840
1
phosphorylation
down-regulates activity
0.351
Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation.
SIGNOR-189045
Q66LE6
O43768
2
binding
down-regulates activity
0.769
We identified cyclic adenosine monophosphate€“regulated phosphoprotein 19 (Arpp19) and -Endosulfine as two substrates of Gwl that, when phosphorylated by this kinase, associate with and inhibit PP2A, thus promoting mitotic entry.
SIGNOR-243735
Q96L92
Q16539
0
phosphorylation
down-regulates activity
0.2
Altogether, our study suggests that MAPK11 and MAPK14 mediate the phosphorylation of SNX27 at Ser51 in vitro and in vivo.
SIGNOR-279069
P11388
P49841
0
phosphorylation
down-regulates quantity by destabilization
0.348
 This study also reports the novel finding that topoIIα may be a target of GSK3β phosphorylation. Evidence suggests that CK2 serves as a priming kinase, through phosphorylation at Ser1365, for GSK3β-mediated phosphorylation at Ser1361.
SIGNOR-276301
Q14524
P61328
2
binding
down-regulates activity
0.579
Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.
SIGNOR-253416
P31749
Q8TDD2
1
phosphorylation
up-regulates
0.423
Akt, a member of the ser-ine/threonine-specific protein kinase, was found to phosphorylate osx and dlx5
SIGNOR-252514
P23467
P35968
1
dephosphorylation
down-regulates activity
0.454
VE-PTP/VEGFR2 complex formation resumes with time, leading to dephosphorylation and deactivation of VEGFR2 (right). B) In VE-PTP-deficient cells, such as after siRNA treatment, VEGFR2 activation (middle) is exaggerated, leading to increased phosphorylation at the Y951 and Y1175 phosphorylation sites
SIGNOR-248441
Q14186
Q14209
2
binding
up-regulates activity
0.738
The transcriptionally active forms of E2F are heterodimers composed of one polypeptide encoded by the E2F gene family and one polypeptide encoded by the DP gene family.In transfected cells, DP-1 did not accumulate in the nucleus unless it was coexpressed with the heterodimeric partners E2F-1, E2F-2, or E2F-3.
SIGNOR-240550
P56693
Q13287
2
binding
up-regulates activity
0.429
we identify an association of Sox10 with the N-myc interactor Nmi. Nmi modulated the transcriptional activity of Sox10 in reporter gene assays. Nmi effects varied between different Sox10 target gene promoters, indicating that Nmi function in vivo may be promoter-specific.
SIGNOR-225599
O14757
O60610
1
phosphorylation
down-regulates activity
0.2
Chk1 Phosphorylates Drf1 for beta-Trcp-Dependent Degradation.|From this we conclude that Chk1 inhibits Drf1, but not the other three limiting factors at the MBT.
SIGNOR-279026
Q06187
Q15417
1
phosphorylation
up-regulates quantity
0.2
Co-expression of calponin-3 with various kinases in S2 Schneider cells promoted a phosphorylation of calponin-3 by Syk, but also by the Tec family kinase Btk.
SIGNOR-280196
Q9NR31
P53992
2
binding
up-regulates quantity
0.709
Biogenesis of COPII vesicles is initiated by the activation of the small guanosine triphosphate (GTP)-binding protein secretion-associated Ras-related protein 1 (Sar1) at specialized subdomains of the ER, called ER exit sites (ERES) or transitional ER (tER). Membrane-bound Sar1 then recruits the inner COPII coat subcomplex, the Sec23/24 heterodimer.
SIGNOR-265302
P29350
Q96P31
2
binding
up-regulates activity
0.39
Tyrosine phosphorylation of SPAP2a by c-Src and in vitro. Tyrosine-phosphorylated SPAP2 is specifically associated with SH2 domain-containing tyrosine kinases Syk and Zap70 and SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2. Site-specific mutagenesis studies revealed that tyrosyl residues 650 and 662 embedded in the ITIMs are responsible for the binding of Syk and Zap70 while tyrosyl residues 692 and 722 embedded in the ITIMs are involved in interactions with SHP-1 and SHP-2.
SIGNOR-274013
P05412
P53779
0
phosphorylation
up-regulates
0.887
With epidermal growth factor treatment, overexpression of erk8 in jb6 cl41 cells caused an increased phosphorylation of c-jun at ser(63) and ser(73), resulting in increased activator protein-1 transactivation.
SIGNOR-164800
O00398
P08754
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-256869
Q16665
Q9Y4C1
1
transcriptional regulation
up-regulates quantity by expression
0.415
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-271568
Q13085
P60510
0
dephosphorylation
up-regulates activity
0.242
PP4 was also found to directly interact with pACC1‑Ser79 in human HepG2 cells. In conclusion, the present study showed that PP4 may be a novel regulator in hepatic lipogenesis through dephosphorylating ACC1 on serine 79, suggesting that PP4 may be a promising therapeutic target in lipid metabolism disorders.
SIGNOR-267724
Q92633
Q14344
2
binding
up-regulates
0.456
The receptor, now called lpa1, is a gpcr that couples to heterotrimeric g proteins (gi, gq, g12/13alpha subunits).
SIGNOR-230761
P01116
P49356
0
null
up-regulates activity
0.419
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-242556
O75581
O00755
2
binding
up-regulates activity
0.648
Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.
SIGNOR-131903
O60729
P12830
1
dephosphorylation
up-regulates activity
0.313
Cdc14B activates APC/C Cdh1 after DNA damage in G2.|Importantly, after DNA damage, thein vivo phosphorylation of wild type Cdh1 - but not that of Cdh1 (4xA) - increased after Cdc14B silencing (XREF_FIG), indicating that in response to genotoxic stress, Cdc14B dephosphorylates Cdh1 on the four sites phosphorylated by Cdk2.
SIGNOR-277017
Q14195
Q92630
0
phosphorylation
up-regulates activity
0.364
Together, these results suggest that crmp4 is able to increase neurite formation and elongation in neurons, although not as potently as crmp2, and that this process is regulated by ser522/ser518/thr514/thr509 phosphorylation in both cases. We demonstrate that cdk5 primes crmp2 and crmp4 for subsequent phosphorylation by gsk3, whereas dyrk2, phosphorylates and primes only crmp4 in vitro
SIGNOR-145987
Q13114
Q96G74
0
deubiquitination
down-regulates activity
0.775
TRAF3 is an E3 ubiquitin ligase that preferentially assembled lysine-63-linked polyubiquitin chains. DUBA selectively cleaved the lysine-63-linked polyubiquitin chains on TRAF3, resulting in its dissociation from the downstream signaling complex containing TANK-binding kinase 1.
SIGNOR-265873
Q9UL17
Q9UL17
2
null
up-regulates
0.2
In turn, T-bet is an IFN-gamma activator (Szabo et al., 2000), thus creating an indirect positive feedback. Furthermore, it has been shown that ectopic T-bet is able to induce the transcription of its own gene
SIGNOR-254294
O14974
Q13464
0
phosphorylation
down-regulates activity
0.774
Phosphorylation by Rho-kinase inhibited MP activity and this reflected a decrease in V(max). Activity of MP with different substrates also was inhibited by phosphorylation. Two major sites of phosphorylation on MYPT1 were Thr(695) and Thr(850).
SIGNOR-249034
O15399
P46934
0
ubiquitination
down-regulates activity
0.328
Nedd4 coexpression with GluN2D enhances GluN2D ubiquitination and reduces GluN1/GluN2D NMDA receptor responses.|This suggests that Nedd4 association reduces GluN2D function, mostly likely by promoting GluN2D ubiquitination and internalization.
SIGNOR-278636
P31391
O00230
2
binding
up-regulates
0.65
Cortistatin is known to bind all five cloned somatostatin receptors and share many pharmacological and functional properties with somatostatin including the depression of neuronal activity.
SIGNOR-82493
P48736
P01375
2
binding
up-regulates
0.296
Tnf activates phosphatidylinositol-3-oh kinase (pi(3)k)
SIGNOR-70625