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P56817
Q9UK22
2
binding
down-regulates quantity by destabilization
0.523
SCFFbx2-E3-ligase-mediated degradation of BACE1 attenuates Alzheimer’s disease amyloidosis and improves synaptic function. We report that the SCF(Fbx2) -E3 ligase is involved in the binding and ubiquitination of BACE1 via its Trp 280 residue of F-box-associated domain. we found that overexpression of Fbx2 in the primary cortical and hippocampal neurons derived from Tg2576 transgenic mice significantly promoted BACE1 degradation and reduced β-amyloid production.
SIGNOR-271904
Q04759
Q8IV61
1
phosphorylation
up-regulates
0.328
Activation of rasgrp3 by phosphorylation of thr-133 is required for b cell receptor-mediated ras activation. our data suggest that pkc, after being activated by diacylglycerol, phosphorylates rasgrp3, thereby contributing to its full activation.
SIGNOR-130490
P29474
P31751
0
phosphorylation
up-regulates activity
0.504
The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites
SIGNOR-251624
Q6DKK2
Q68DK2
2
binding
up-regulates activity
0.462
We show that PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26), and its binding partner TTC19, which in turn interacts with CHMP4B, an endosomal sorting complex required for transport (ESCRT)-III subunit implicated in the abscission step of cytokinesis. On the basis of these data and the high-content microscopy described above, we propose that PtdIns(3)P controls the KIF13A-dependent recruitment of FYVE-CENT and TTC19 to the midbody, and that TTC19 is the most downstream effector of the three, possibly controlling the function of CHMP4B. FYVE-CENT binds directly to TTC19 and KIF13A.
SIGNOR-265542
P49815
O75592
0
ubiquitination
down-regulates quantity by destabilization
0.356
We show that Pam associates with E2 ubiquitin conjugating enzymes, and tuberin can be ubiquitinated by Pam through its RING finger domain.
SIGNOR-278704
Q969H0
P23771
1
ubiquitination
down-regulates quantity by destabilization
0.403
Fbw7 promotes degradation of GATA3 in a Thr-156-dependent manner. 
SIGNOR-276635
P28482
O00562
1
phosphorylation
up-regulates
0.2
Both cdk1 and erk2 induced phosphorylation of the wild-type nir2. Substitution of t794 by alanine reduced the phosphorylation by erk2, whereas the double mutations t794/1223a completely abolished it. The requirement of multiple nir2 phosphorylation sites for plk1 binding may provide a mechanism that sets a threshold for the nir2-plk1 interaction during mitosis.
SIGNOR-124646
P50148
P46663
2
binding
up-regulates activity
0.589
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-257304
Q7Z6M1
P11717
1
relocalization
up-regulates activity
0.385
P40 is a very potent transport factor in that the pure, recombinant protein can stimulate, significantly, an in vitro transport assay that measures transport of mannose 6-phosphate receptors from endosomes to the trans-Golgi network. The functional importance of p40 is confirmed by the finding that anti-p40 antibodies inhibit in vitro transport. Finally, p40 shows synergy with Rab9 in terms of its ability to stimulate mannose 6-phosphate receptor transport. These data are consistent with a model in which p40 and Rab9 act together to drive the process of transport vesicle docking.
SIGNOR-253090
O95433
P00519
0
phosphorylation
up-regulates activity
0.251
Here, we show that c-Abl kinase phosphorylates Y223 in human Aha1 (hAha1), promoting its interaction with Hsp90. This, consequently, results in an increased Hsp90 ATPase activity
SIGNOR-260938
Q13627
Q12778
1
phosphorylation
down-regulates
0.506
Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity.
SIGNOR-183670
P67775
Q04206
1
dephosphorylation
down-regulates
0.483
Rela was dephosphorylated by a purified pp2a core enzyme, a heterodimer formed by the catalytic subunit of pp2a (pp2ac) and pr65, in a concentration-dependent manner.These data suggest that the constitutive activation of rela in melanoma cells could be due, at least in part, to the deficiency of pp2a, which exhibits decreased dephosphorylation of nf-kappa b/rela.
SIGNOR-110959
Q92900
P31749
0
phosphorylation
up-regulates activity
0.257
AKT-Mediated UPF1 Phosphorylation at T151 Promotes UPF1 Helicase Activity
SIGNOR-277597
P68400
O60936
1
phosphorylation
up-regulates activity
0.324
Phosphorylation of ARC at T149 Is Required for Its Antiapoptotic Effect. Here we report that the function of ARC is regulated by protein kinase CK2. ARC at threonine 149 is phosphorylated by CK2. This phosphorylation targets ARC to mitochondria. ARC is able to bind to caspase-8 only when it is localized to mitochondria but not to the cytoplasm.
SIGNOR-262837
Q15418
O15530
0
phosphorylation
up-regulates activity
0.63
Full-length RSK1, RSK2, and RSK3 Are Activated when Coexpressed with PDK1 in COS7 Cells. Ser221 phosphorylation is increased 2–3-fold during ERK-mediated activation of RSK1 in COS1 cells
SIGNOR-250270
P21127
Q96I25
1
phosphorylation
up-regulates activity
0.207
However, Clk1 enhanced SPF45 protein expression, but not mRNA expression, whereas inhibition of Clk1 increased SPF45 degradation through a proteasome dependent pathway.|In the present work, we show that Clk1 phosphorylates SPF45 in vitro on eight serine residues, all of which are N-terminal to the RRM domain required for splicing.
SIGNOR-279510
P35222
Q96EB6
0
deacetylation
up-regulates quantity
0.505
SIRT1 deacetylates β-catenin to promote its accumulation in the nucleus and thus induces the transcription of genes that block MSC adipogenesis.
SIGNOR-256208
P63000
Q7Z5H3
0
gtpase-activating protein
down-regulates activity
0.529
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-260477
Q9Y5I2
P05556
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-265664
P49841
O95997
1
phosphorylation
down-regulates activity
0.2
Glycogen synthase kinase-3beta (GSK3beta) negatively regulates PTTG1 and human securin protein stability, and GSK3beta inactivation correlates with securin accumulation in breast tumors.|Here, we demonstrate that glycogen synthase kinase-3\u03b2 (GSK3\u03b2) phosphorylates securin to promote its proteolysis via SCF(\u03b2TrCP) E3 ubiquitin ligase.
SIGNOR-279188
P36873
P29474
1
dephosphorylation
up-regulates activity
0.2
The increase in eNOS activity coincided with specific dephosphorylation of eNOS-Thr495, known to enhance eNOS activity. Inhibition of protein phosphatase 1 (PP1) by calyculin A, tautomycetin, or siRNA against PP1 reversed NF-induced eNOS-Thr495 dephosphorylation
SIGNOR-248501
P05771
O75144
1
phosphorylation
up-regulates activity
0.2
PKCα and PKCβ are required for phosphorylation of ICOSL and ICOSL-mediated cytokine induction 
SIGNOR-273797
Q01974
P41221
2
binding
up-regulates
0.775
Wnt5a induces ROR1/ROR2 heterooligomerization to enhance leukemia chemotaxis and proliferation|Evolutionarily conserved receptor tyrosine kinase–like orphan receptor-1 and -2 (ROR1/2) are considered distinct receptors for Wnt5a and are implicated in noncanonical Wnt signaling in organogenesis and cancer metastasis.
SIGNOR-199647
P00519
Q06609
1
phosphorylation
up-regulates activity
0.773
C-Abl phosphorylates Rad51 in vitro and in vivo. phosphorylation of Rad51 by c-Abl enhances complex formation between Rad51 and Rad52, which cooperates with Rad51 in recombination and repair. c-Abl phosphorylates Rad51 Tyr315
SIGNOR-251434
P63092
P25105
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-256789
Q96PG8
P04626
0
phosphorylation
down-regulates activity
0.281
These results show for the first time that PUMA can be phosphorylated at tyrosine residues directly by HER2.|Together, our results demonstrate, for the first time, that PUMA can be tyrosine phosphorylated and that HER2-mediated phosphorylation destabilizes PUMA protein.
SIGNOR-278224
P68400
P41002
1
phosphorylation
down-regulates activity
0.249
We determined that casein kinase II (CK2) can phosphorylate Ser621 and thereby regulate the E3 ligase activity of the SCF(cyclin F) complex.
SIGNOR-266373
Q09472
P06493
0
phosphorylation
down-regulates quantity by destabilization
0.404
In this study, we found that p300 was highly phosphorylated and its level was decreased during mitosis and tumorigenesis. In vitro and in vivo experiments aimed showed that cyclin-dependent kinase 1 (CDK1) and ERK1/2 phosphorylated p300 on Ser1038 and Ser2039. Mutations of Ser1038 and Ser2039 increased p300 protein stability and levels. 
SIGNOR-276457
O95295
P60880
2
binding
up-regulates activity
0.582
In the present study, we used yeast two-hybrid analysis to identify a new binding partner of torsinA, the SNARE-associated protein snapin. We have reported that snapin shows a robust interaction with wild type and mutant torsinA. we have demonstrated that this portion of torsinA and/or the adjacent linker region has the additional role of recruiting snapin. we found that snapin, which binds SNAP-25 (synaptosome-associated protein of 25,000 Da) and enhances the association of the SNARE complex with synaptotagmin, is an interacting partner for both wild type and mutant torsinA.
SIGNOR-261171
P63279
P03230
2
binding
up-regulates activity
0.2
One mechanism by which LMP1 regulates cellular activation is through the induction of protein posttranslational modifications. We have now identified a specific target of LMP1-induced sumoylation, interferon regulatory factor 7 (IRF7). We hypothesize that during EBV latency, LMP1 induces the sumoylation of IRF7, limiting its transcriptional activity and modulating the activation of innate immune responses. We recently documented that LMP1 induces a third major protein modification by physically interacting with the SUMO-conjugating enzyme Ubc9 through CTAR3 and inducing the sumoylation of cellular proteins in latently infected cells. we identified that IRF7 is sumoylated at lysine 452.
SIGNOR-266838
Q15173
P31749
1
dephosphorylation
down-regulates
0.661
Activation of pp2a is the intermediate step between the abeta-ceramide cascade and the subsequent inactivation of akt.
SIGNOR-252615
Q07812
Q9BXH1
0
relocalization
up-regulates
0.49
Puma promotes bax translocation by both by directly interacting with bax and by competitive binding to bcl-x(l) in uv-induced apoptosis.
SIGNOR-185671
O15034
Q9UJD0
2
binding
down-regulates activity
0.282
SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.
SIGNOR-264371
O60716
P17612
0
phosphorylation
down-regulates
0.2
We showed that pkc_ phosphorylation of p120 at serine (s)879 in response to thrombin or lipopolysaccharide challenge reduced p120 binding affinity for ve-cadherin and mediated aj disassembly secondary to ve-cadherin internalization
SIGNOR-198288
P28336
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-257248
Q13043
Q13043
2
phosphorylation
up-regulates activity
0.2
Mapping of MST1 kinase sites of phosphorylation. Activation and autophosphorylationWe define Thr(183) in subdomain VIII as a primary site of phosphoactivation. Thr(187) is also critical for kinase activity.
SIGNOR-247581
Q9HCE7
O43541
2
relocalization
down-regulates activity
0.831
Smurf1, with its WW domain, specifically binds to the PY motif of Smad6 and transports Smad6 into the cytoplasm.
SIGNOR-105931
O60763
P62820
2
binding
up-regulates activity
0.798
Here, the tethering factor p115 was shown to be a Rab1 effector that binds directly to activated Rab1.
SIGNOR-261287
P35916
Q04760
1
phosphorylation
up-regulates activity
0.2
We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).
SIGNOR-276180
Q13131
P26358
1
phosphorylation
down-regulates activity
0.2
Together, these results indicate that AMPK phosphorylated DNMT1-Ser730, RBBP7-Ser314, and HAT1-Ser190|AMPK decreased DNMT1 activity
SIGNOR-264783
Q7Z6Z7
Q13105
1
ubiquitination
down-regulates quantity by destabilization
0.327
Previously, we reported that K48 linked polyubiquitination of Miz1 by Mule triggers its proteasomal degradation, thereby relieving Miz1 suppression on TNF induced JNK activation and apoptosis.
SIGNOR-278697
P06493
O43148
1
phosphorylation
up-regulates activity
0.255
We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor.
SIGNOR-265501
P17252
Q14432
1
phosphorylation
up-regulates
0.2
Protein kinase c-mediated phosphorylation and activation of pde3a regulate camp levels in human platelets. together, these results demonstrate that platelet activation stimulates pkc-dependent phosphorylation of pde3a on ser(312), ser(428), ser(438), ser(465), and ser(492) leading to a subsequent increase in camp hydrolysis and 14-3-3 binding.
SIGNOR-184452
P25101
P63096
2
binding
up-regulates activity
0.406
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-257052
O75581
P27361
0
phosphorylation
up-regulates
0.313
We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6.
SIGNOR-169004
P63096
P49683
2
binding
up-regulates activity
0.278
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-256694
Q16513
P61586
2
binding
up-regulates activity
0.833
PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome.
SIGNOR-275466
P10636
Q5TCY1
0
phosphorylation
down-regulates
0.451
Direct tau phosphorylation by ttbk1 at ser198, ser199, ser202 and ser422, which are also phosphorylated in phfs. Ttbk1 also induces tau aggregation in human neuronal cells in a dose-dependent manner. We conclude that ttbk1 is a neuron-specific dual kinase involved in tau phosphorylation at ad-related sites and is also associated with tau aggregation.
SIGNOR-148970
P52564
P53778
1
phosphorylation
up-regulates
0.659
Mapkk6 was shown to phosphorylate and specifically activate the p38/mpk2 sub of the mitogen-activated protein kinase superfamily . the p38 mapkinasekinasemkk6 is identified as a common activator of p38 alpha, p38 beta 2, and p38 gamma mapkinaseisoforms . p38mapks are activated by dual phosphorylation on a t-x-y motif in the activation loop through the action of map kinase kinases
SIGNOR-184134
Q13237
P04792
1
phosphorylation
down-regulates
0.2
Purified pkg isoforms ia, ib, and ii all caused incorporation of phosphate in recombinant hsp27 at ser-78, ser-82, and thr-143, but not ser-15.These Studies indicate that hsp27 is a genuine substrate for pkg and that pkg may mediate inhibition of platelet aggregation through phosphorylation of hsp27 and subsequent prevent of actin polymerization
SIGNOR-186947
P67809
P53350
0
phosphorylation
up-regulates quantity
0.253
Here we identify that PLK1 inhibition can induce apoptosis and DNA damage of GSCs, we have also delineat the possible underlying molecular mechanisms: PLK1 interacts with YBX1 and directly phosphorylates serine 174 and serine 176 of YBX1.|Inhibition of PLK1 reduces the phosphorylation level of YBX1, and decreased phosphorylation of YBX1 prevents its nuclear translocation, thereby inducing apoptosis and DNA damage of GSCs.
SIGNOR-279255
P58400
Q8NFZ4
2
binding
up-regulates activity
0.825
The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites
SIGNOR-265453
O95644
P53779
0
phosphorylation
down-regulates
0.445
We show that jnk, erk, and p38 physically associate with the nfatc n-terminal regulatory domain and can directly phosphorylate functionally important residues involved in regulating nfatc subcellular localization, namely ser(172) and the conserved nfatc ser-pro repeats.
SIGNOR-74556
Q68DV7
Q14332
1
relocalization
up-regulates
0.308
Frizzled receptors are regu__lated by cycles of ubiquitylation and deubiquitylation61 (see above), and znrf3 and rnf43 act as frizzled ubiquitin ligases, removing frizzled and possibly lrp6 from the plasma membrane
SIGNOR-199585
P51955
Q76N32
1
phosphorylation
down-regulates quantity by destabilization
0.251
In this study we show phosphorylation of Cep68 by Nek2 creates a potential phosphodegron that directs Cep68 destruction through the activity of SCF-beta-Trcp.|Our above results showed that Nek2 promoted mitotic degradation of Cep68.
SIGNOR-279471
Q92794
P10147
1
transcriptional regulation
up-regulates quantity by expression
0.2
We further demonstrate that the histone acetyltransferase, MOZ, can activate the MIP-1a promoter in T-cells and that this activation is largely dependent upon the proximal RUNX site. Moreover, we show that co-expression of MOZ and RUNX1 can activate the MIP-1a promoter.
SIGNOR-251726
O15379
P49327
1
deacetylation
up-regulates quantity by stabilization
0.2
Overexpression of HA-HDAC3 decreased the acetylation level of endogenous FASN by 35% in HEK293T cells, while the expression of a catalytic inactive mutant HDAC3Y298H (38) failed to reduce FASN acetylation (Fig. 4C). Conversely, HDAC3 knockdown increased the acetylation level of endogenous FASN by >1.5-fold in HEK293T cells
SIGNOR-267367
Q9P2J9
Q15797
1
dephosphorylation
down-regulates
0.243
We show that the mammalian pdps are important in dephosphorylation of bmp-activated smad1 but not tgf-beta-activated smad2 or smad3. Thus, pdps specifically inactivate smads in the bmp/dpp pathway. [...] These observations suggest that pdp1 and pdp2 are important for dephosphorylation of smad1.
SIGNOR-144909
Q01105
P12544
0
cleavage
down-regulates
0.711
Gzma cleaved the nucleosome assembly protein set after lys176 and disrupted its nucleosome assembly activity.
SIGNOR-110462
P10828
P19793
2
binding
up-regulates
0.721
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-81449
Q53G59
O94979
2
binding
up-regulates activity
0.606
By analyzing mouse embryonic stem cell (mESC) division, we have identified Cul3Klhl12 as a regulator of COPII coat formation. Cul3Klhl12 monoubiquitinates Sec31 and drives assembly of large COPII-coats. As a result, ubiquitination by Cul3Klhl12 is essential for collagen export, a step that is required for integrin-dependent mESC division.
SIGNOR-272010
P60510
Q13263
1
dephosphorylation
down-regulates activity
0.358
PP4 dephosphorylated pKAP1 in vitro.
SIGNOR-277163
O60832
O14746
2
binding
up-regulates activity
0.815
Dyskerin was recently found to be associated with active human telomerase (34), and mutations in dyskerin or NOP10 or deletion of the H/ACA motif of hTERC result in diminished telomerase activity
SIGNOR-263332
P24941
Q05516
1
phosphorylation
down-regulates
0.282
Here we show that the main cyclin-dependent kinase involved at the g(1) to s transition (cdk2) phosphorylates plzf at two consensus sites found within pest domains present in the hinge region of the protein. This phosphorylation triggers the ubiquitination and subsequent degradation of plzf, which impairs plzf transcriptional repression ability and antagonizes its growth inhibitory effects.
SIGNOR-160630
Q16666
P68400
0
phosphorylation
up-regulates activity
0.321
Here we examine the functionality of the interferon-induced factor 16 (IFI 16) CcN motif, demonstrating its ability to target a heterologous protein to the nucleus, and to be phosphorylated specifically by the CcN-motif-phosphorylating protein kinase CK2 (CK2). | Specific phosphorylation of IFI 16 Ser132 in HeLa cell extracts and by purified CK2 in vitro
SIGNOR-250902
Q99677
O95837
2
binding
up-regulates activity
0.385
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-257432
P41225
P35222
2
binding
down-regulates
0.497
Two additional sox proteins, xsox17alfa and xsox3, likewise bind to beta-catenin and inhibit its tcf-mediated signaling activity.
SIGNOR-72039
P30281
Q15759
0
phosphorylation
down-regulates quantity by destabilization
0.2
P38SAPK2 phosphorylates cyclin D3 at Thr-283 and targets it for proteasomal degradation.
SIGNOR-280023
Q13164
P37231
2
binding
up-regulates activity
0.377
In endothelial cells, flow-mediated activation of ERK5 has been shown to lead to activation of PPAR gamma by direct binding to the hinge-helix region of PPAR gamma
SIGNOR-278108
P67775
Q13362
2
binding
up-regulates activity
0.864
We have identified by two-hybrid interaction a new human gene family encoding PP2A B subunits. This family, denoted B56, contains three distinct genes, one of which is differentially spliced.
SIGNOR-268155
P09471
P51582
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-257006
Q96BD5
O60341
2
binding
down-regulates activity
0.716
BHC80 Inhibits LSD1 Demethylase Activity In Vitro. in contrast to CoREST, which is a positive regulator of LSD1 activity, the in vitro evidence presented above suggests that BHC80 may function to inhibit LSD1 activity.
SIGNOR-264505
Q14596
Q9H492
2
binding
up-regulates
0.559
We performed glutathione s-transferase (gst) pull-down assays using extracts from hek293 cells overexpressing an ha-tagged nbr1(d50r) mutant, which lacks the ability to bind p62 (lamark et al., 2003) and gst fusions of six human atg8 homologs: gabarap, gabarapl1, gabarapl2, lc3a, lc3b, and lc3c. Indeed, nbr1 interacted with all these members of the mammalian atg8 protein family.
SIGNOR-184270
P01241
O60281
0
transcriptional regulation
up-regulates quantity by expression
0.2
Rat Zn-15 is a transcription factor activating GH gene expression by synergistic interactions with Pit-1, named for 15 DNA-binding zinc fingers, including fingers IX, X, and XI that are responsible for GH promoter binding.
SIGNOR-268969
P00533
P29353
2
binding
up-regulates activity
0.913
Adaptors such as Shc, Grb2, Crk or the recently characterised Dok-R protein (Jones Dumont 1999) show a modular structure containing protein– protein interaction domains and putative phosphorylation sites and act as signalling platforms which extend the receptor’s repertoire of activated intracellular pathways.
SIGNOR-107712
Q9UJT0
Q8IYT4
2
binding
down-regulates quantity by destabilization
0.2
KATNAL2 does not sever microtubules composed of α- and β-tubulin but does interact with δ- and ε-tubulin
SIGNOR-267176
O14744
P31269
1
methylation
up-regulates activity
0.462
Hoxa9 methylation by prmt5 is essential for endothelial cell expression of leukocyte adhesion molecules. / prmt5 is a critical coactivator component in a newly defined, hoxa9-containing transcription complex./ Hoxa9 is methylated on arg140 by prmt5.
SIGNOR-195526
P78337
Q9UBX2
0
transcriptional regulation
up-regulates quantity by expression
0.307
DUX4, a candidate gene of facioscapulohumeral muscular dystrophy, encodes a transcriptional activator of PITX1
SIGNOR-261590
Q12778
O75874
1
transcriptional regulation
up-regulates quantity by expression
0.258
We identify FOXOs as transcriptional activators of IDH1. FOXOs promote IDH1 expression and thereby maintain the cytosolic levels of α-ketoglutarate and NADPH.
SIGNOR-260101
Q96LB2
P63096
2
binding
up-regulates activity
0.249
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-257058
P43694
Q9UI47
1
transcriptional regulation
up-regulates quantity by expression
0.25
GATA-4 and MEF2C are known to bind to the GATA box 2 in the major promoter of CTNNA3 and this element is essential in directly regulating expression of CTNNA3 in cardiac muscle cells. The co-transfection of GATA-4 with MEF2C leads to a synergistic activation of the CTNNA3 promoter
SIGNOR-265490
P50148
Q8N1W1
2
binding
up-regulates activity
0.291
Taken together, the results suggest that active G13 and Gq form a complex with Rgnef and that G13 and Gq are upstream activators of Rgnef.
SIGNOR-278065
Q13114
Q86VP1
2
binding
down-regulates activity
0.466
ABIN1 interacted with the A20 regulatory molecule TAX1BP1 and was essential for the recruitment of TAX1BP1 and A20 to the noncanonical IkappaB kinases TBK1 and IKKi in response to poly(I:C) transfection. ABIN1 and TAX1BP1 together disrupted the interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKKi to attenuate lysine 63-linked polyubiquitination of TBK1/IKKi.
SIGNOR-275737
P17987
P52747
0
transcriptional regulation
up-regulates quantity by expression
0.279
The transcription from the minimalCcta promoter was up-regulated 3-fold by ZNF143 and 6-fold by ZNF76 when full-length proteins were co-expressed, indicating that both ZNF143 and ZNF76 can enhance Ccta transcription.
SIGNOR-266220
P51681
P10147
2
binding
up-regulates activity
0.745
The purpose of this study was to determine whether certain chemokines, which are highly expressed in injured skeletal muscle, are involved in the repair and functional recovery of the muscle after traumatic injury. In wild-type control mice, mRNA transcripts of macrophage inflammatory protein (MIP)-1􏰂, MIP-1􏰃, and monocyte chemoattractant protein (MCP)-1 as well as their major receptors, CCR5 and CCR2, increased after freeze injury and gradu- ally returned to control (uninjured) levels by 14 days.
SIGNOR-251724
Q15418
P27361
0
phosphorylation
up-regulates activity
0.718
Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity.Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3.
SIGNOR-102648
P01106
Q9BZ95
2
binding
up-regulates quantity by stabilization
0.2
Indeed, dose-dependent TR-FRET and affinity pull-down assay confirmed the interaction of NSD3-s with MYC. Supporting functional significance of the interaction, co-expression of NSD3-s, but not the MYC-binding defective fragment of NSD3-s (1–347), stabilized MYC protein and increased MYC transcriptional activity as revealed by a MYC-driven reporter assay.
SIGNOR-259199
P08123
Q8IYK4
0
glycosylation
up-regulates activity
0.4
Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.
SIGNOR-261157
P13569
Q13131
0
phosphorylation
down-regulates activity
0.493
AMPK phosphorylates CFTR¬†in vitro¬†at two essential serines (Ser737and Ser768) in the R domain, formerly identified as "inhibitory" PKA sites.|Interestingly two of these sites, namely Ser737 and Ser768, have been identified as “inhibitory” R domain sites, i.e. when mutated to alanines they augment the open probability of CFTR relative to wild type|Our present results suggest that it might be AMPK rather than PKA that is phosphorylating Ser737 and Ser768 under baseline conditions
SIGNOR-259858
Q12860
P78357
0
relocalization
up-regulates activity
0.625
These results suggest that the targeting of contactin to different axonal domains may be determined, in part, via its association with Caspr.
SIGNOR-269073
P54764
O43921
2
binding
up-regulates
0.924
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-52203
Q14344
P25101
2
binding
up-regulates
0.557
We studied the ability of et receptors to activate galfa13 using an assay for g protein alfa-chain activation that is based on the fact that an activated (gtp-bound) alfa-chain is resistant to trypsinization compared with an inactive (gdp-bound) alfa-chain.
SIGNOR-66856
P00519
P0DP91
1
phosphorylation
up-regulates activity
0.271
These data raise the possibility that tyrosine phosphorylation of CSB by c-Abl promotes redistribution of CSB in the nucleus and enrichment of CSB in the nucleolus in response to oxidative stress
SIGNOR-279317
P40763
P54762
0
phosphorylation
up-regulates activity
0.353
By integrating mouse in vivo and in vitro models with human iPSC derived astrocytes, we provide direct evidence that EphB1 can induce early astrocytic STAT3 activation via ephrin-B1 signalling.|We confirmed that EphB1 activates astrocytes by inducing ephrin-B1 dependent STAT3 phosphorylation.
SIGNOR-279709
Q13200
Q12851
0
phosphorylation
up-regulates activity
0.2
Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B). 
SIGNOR-273900
O15350
Q9P2P5
0
ubiquitination
up-regulates quantity by stabilization
0.37
P73 was efficiently ubiquitinated but stabilized in a NEDL2-dependent manner. Accordingly, p73 decayed at faster rates in the absence of NEDL2 than in its presence. Consistent with the NEDL2-mediated stabilization of p73, NEDL2 enhanced the p73-dependent transcriptional activation. Thus, our results suggest that NEDL2 activates the function of p73 by increasing its stability.
SIGNOR-269457
P45973
Q5XPI4
0
polyubiquitination
down-regulates quantity by destabilization
0.2
In the present study, we report that HP1α and β undergo proteasomal degradation in lamin A/C knock-down cells and show by ectopic expression, RNAi and binding studies that the RING finger ubiquitin ligase RNF123 is directly involved in HP1 degradation.
SIGNOR-272035
Q15831
Q13153
1
phosphorylation
down-regulates
0.247
Lkb1 suppresses p21-activated kinase-1 (pak1) by phosphorylation of thr109 in the p21-binding domain.
SIGNOR-164814
Q13315
Q99638
1
phosphorylation
up-regulates activity
0.767
Hyperphosphorylation of hrad9 induced by ir is dependent on atm. Ser(272) of hrad9 is phosphorylated directly by atm in vitro. / our results suggest that the atm-mediated phosphorylation of hrad9 is required for ir-induced checkpoint activation.
SIGNOR-105243
Q96R06
Q9UNH5
0
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