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Q9Y5B0
P30291
1
dephosphorylation
up-regulates activity
0.382
At mitosis exit, Fcp1 promoted inhibitory Cdk1 phosphorylation by dephosphorylating Wee1, and ubiquitin dependent cyclin B degradation by dephosphorylating Cdc20 and USP44.|This lead us to hypothesize that, during prolonged mitosis in AMCDs treated cancer cells, progressive Fcp1 induced Wee1 reactivation might lead to ...
SIGNOR-277142
Q05513
O95863
1
phosphorylation
down-regulates quantity by destabilization
0.2
APKC kinases phosphorylate S249 of SNAI1, which leads to protein degradation.
SIGNOR-277437
P56962
Q9H714
2
binding
up-regulates activity
0.2
Under nutrient-rich conditions, mTORC1 phosphorylates Pacer at serine157 to disrupt the association of Pacer with Stx17 and the HOPS complex and thus abolishes Pacer-mediated autophagosome maturation. These results demonstrate that mTORC1-mediated Pacer phosphorylation at S157 inhibits autophagosome maturation by disru...
SIGNOR-273684
Q99538
P07900
2
binding
up-regulates quantity by stabilization
0.2
We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90α to subsequently promote pro-AEP intracellular stability as well as secretion. We now present evidence that AEP is a substrate for TRAF6 ubiquitination, resulting in AEP/TRAF6...
SIGNOR-272855
P0C0S8
Q5FBB7
1
relocalization
up-regulates activity
0.2
The complex between shugoshin and protein phosphatase 2A (Sgo1-PP2A) localizes to centromeres in mitosis, binds to cohesin in a reaction requiring Cdk-dependent phosphorylation of Sgo1, dephosphorylates cohesin-bound sororin, and protects a centromeric pool of cohesin from mitotic kinases and the cohesin inhibitor Wapl...
SIGNOR-265262
Q7Z434
Q14164
2
binding
up-regulates activity
0.832
After ligand binding, cGAS and RIG-I signal through respective adaptor proteins STING and MAVS to recruit the kinases IKK and TBK1, which then activate the transcription factors NF-κB and interferon regulatory factor 3 (IRF3), respectively.
SIGNOR-260144
Q13322
P06213
2
binding
down-regulates
0.66
Grb10 negatively regulates growth factor signaling. It binds the insulin and insulin-like growth factor 1 (igf-1) receptors;mice without grb10 are larger and exhibit enhanced insulin sensitivity.
SIGNOR-174065
Q16620
Q92529-2
1
phosphorylation
up-regulates activity
0.755
We also obtained tryptic phosphopeptide maps of N-Shc protein phosphorylated in vitro by other tyrosine kinases, TrkB, v-Src and EGFR. The overall patterns of the phosphopeptide maps generated by these tyrosine kinases were similar, although there were some differences among these maps (Figure 4a–d).We performed phosph...
SIGNOR-273917
Q9UQF2
Q12851
2
binding
down-regulates
0.2
DLK mutants were used to demonstrate that a DLK leucine zipper-leucine zipper interaction is necessary for DLK dimerization and to show that DLK dimerization mediated by the leucine zipper domain is prerequisite for DLK activity and subsequent activation of stress-activated protein kinase (SAPK).
SIGNOR-75385
Q14344
Q9NZN5
2
binding
up-regulates activity
0.772
P115 RhoGEF stimulates the intrinsic GTP hydrolysis activity of G alpha 12/13 subunits and acts as an effector for G13-coupled receptors by linking receptor activation to RhoA activation.
SIGNOR-256519
O00303
P21127
0
phosphorylation
up-regulates activity
0.515
EIF3f is phosphorylated by CDK11p46 at Ser46 during apoptosis.|Phosphorylation of eIF3f plays an important role in regulating its function in translation and apoptosis. Phosphorylation of eIF3f enhances the association of eIF3f with the core eIF3 subunits during apoptosis. 
SIGNOR-273133
P11802
Q8IZL8
1
phosphorylation
up-regulates
0.351
Using site-directed mutagenesis and in vitro kinase assays, we identified ser(477) and ser(991) of pelp1 as cdk phosphorylation sites. we identified pelp1 as a novel substrate of cdks and found that cdk phosphorylation is important for the proper function of pelp1 in modulating hormone-driven cell cycle progression an...
SIGNOR-167770
O43318
Q9Y572
1
phosphorylation
up-regulates activity
0.2
Collectively, TAK1 activates RIPK3, RIPK3 activates TAK1, and RIPK1 activates RIPK3 and facilitates interaction between TAK1 and RIPK3.|We found that prolonged and hyperactivation of TAK1 induced phosphorylation and activation of RIPK3, leading to necrosis without caspase activation.
SIGNOR-279634
Q9H714
P56962
2
binding
up-regulates activity
0.2
Under nutrient-rich conditions, mTORC1 phosphorylates Pacer at serine157 to disrupt the association of Pacer with Stx17 and the HOPS complex and thus abolishes Pacer-mediated autophagosome maturation. These results demonstrate that mTORC1-mediated Pacer phosphorylation at S157 inhibits autophagosome maturation by disru...
SIGNOR-273684
P84022
O15105
0
transcriptional regulation
down-regulates quantity
0.613
The downstream molecules including mad2, smad3, smad4 and smad7 are involved in TGF-β1-induced EMT,while Smad7 blocks the smad3 expression
SIGNOR-260437
Q14790
P29350
0
dephosphorylation
up-regulates activity
0.354
Caspase-8 is tyrosine-phosphorylated in freshly isolated neutrophils but spontaneously dephosphorylates in culture, in association with the progression of constitutive apoptosis. Phosphorylation of caspase-8 on Tyr-310 facilitates its interaction with the Src-homology domain 2 containing tyrosine phosphatase-1 (SHP-1) ...
SIGNOR-248478
P00519
P40763
1
phosphorylation
up-regulates activity
0.445
Previously, we showed that c-Abl and Arg promote phosphorylation of the STAT3 transcription factor (Y705) in a variety of cancer cell lines , .|Since c-Abl and Arg activate STAT3, we investigated whether c-Abl and Arg regulate NF-kappaB signaling.
SIGNOR-279675
O15503
Q8WU17
0
ubiquitination
down-regulates quantity
0.477
TRC8/RNF139 encodes an endoplasmic reticulum-resident E3 ubiquitin ligase that inhibits growth in a RING- and ubiquitylation-dependent manner. TRC8 also contains a predicted sterol-sensing domain. Here, we report that TRC8 protein levels are sterol responsive and that it binds and stimulates ubiquitylation of the endop...
SIGNOR-271955
P19784
Q8N163
1
phosphorylation
up-regulates activity
0.2
CK2alphawas bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2alphawas evidenced by co-immunoprecipitation of CK2alphaand DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. |In our results, CK2alpha affected the|These results suggest that DBC1 may be involve...
SIGNOR-267667
P41968
Q8TCY5
2
binding
down-regulates activity
0.474
We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression...
SIGNOR-252366
P38936
P31751
2
binding
down-regulates activity
0.682
Whereas akt1 phosphorylates p21, inducing its release from cdk2 and cytoplasmic localization as previously described for akt, akt2 binds p21 in the region spanning the t145 site of p21, thus competing with phosphorylation by akt1 and inducing its accumulation in the nucleus. These distinct roles of akt/pkb isoforms in ...
SIGNOR-149705
Q06124
P32927
1
dephosphorylation
up-regulates
0.511
Shp2 is thought to act as a positive mediator of growth factor signals.. Hp2 could act as an adaptor between the activated c and grb2, thus leading to activation of the ras/mitogen-activated protein kinase pathway, known to be activated by il-3
SIGNOR-48557
P25098
P00533
0
phosphorylation
up-regulates activity
0.2
Previous studies showed that EGFR activation results in association of GRK2 with the EGFR and subsequent phosphorylation of GRK2 at three tyrosine residues (Tyr 13, -86, and -92), resulting in activation of GRK2.|We propose that GRK2 activation by EGFR leads to GRK2 phosphorylation of Mst2 at these sites, which, in tur...
SIGNOR-279368
P53350
Q14674
1
phosphorylation
down-regulates activity
0.772
Although mutation of serine 1126 and threonine 1346 to alanine had no effect (lanes 2 and 5), additional mutation of threonine 1363 and serine 1399 rendered separase almost completely resistant to phosphorylation (lane 3). Serine 1399 seems to be the one residue within this large separase fragment that is most efficien...
SIGNOR-276082
P31749
A8MYZ6
1
phosphorylation
down-regulates
0.648
The phosphorylation of the two remaining akt-dependent sites inhibits foxo6 transcriptional activity
SIGNOR-252582
Q04759
Q00613
1
phosphorylation
up-regulates
0.349
At the same time, ea causes pkc?-Mediated phosphorylation and activation of the transcription factor heat shock factor 1, an inducer of glucose dependence.
SIGNOR-200576
Q8N3Y1
P24385
2
binding
down-regulates quantity by destabilization
0.511
We next investigated whether in vitro ubiquitination of cyclin D1 through the SCF-like (SCFL) complex FBXW8 (SKP1-CUL7-FBXW8-RBX1/SCFLFBXW8) requires phosphorylation of cyclin D1 at Thr286 (Fig. 3F). Polyubiquitination through SCFLFBXW8 was dramatically reduced by the depletion of ERK2 (lane 2). Furthermore, cyclin D1 ...
SIGNOR-271624
Q9NYV6
P45984
0
phosphorylation
down-regulates
0.472
Inactivation is due to phosphorylation of tif-ia by c-jun n-terminal kinase (jnk) at a single threonine residue (thr 200). Phosphorylation at thr 200 impairs the interaction of tif-ia with pol i and the tbp-containing factor tif-ib/sl1, thereby abrogating initiation complex formation.
SIGNOR-134878
P08754
Q96LB2
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- signali...
SIGNOR-257171
Q99717
Q13464
0
phosphorylation
up-regulates activity
0.306
The results showed that SMAD5 was directly phosphorylated at Ser463/465 by ROCK1 (Fig.\u00a04g).|These data indicated that the activation of SMAD5 induced by TEM8 was mediated directly by the RhoC/ROCK1 pathway.To evaluate the effect of SMAD5 on the cellular functions of TEM8, SMAD5 was knockdown in TEM8-overexpressi...
SIGNOR-280107
Q16611
Q16611
2
binding
up-regulates
0.2
Allosteric activation of bak induces its intramembranous oligomerization into a proposed pore for cytochrome c efflux
SIGNOR-105203
Q05655
Q00535
1
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
Q96TA1
P15056
0
phosphorylation
down-regulates activity
0.2
Overall, this indicates that BRAF-dependent phosphorylation of FAM129B controls its cellular localization and thus its ability to bind to KEAP1 to block NRF2 degradation.
SIGNOR-279595
Q9BYW2
P68431
1
trimethylation
up-regulates activity
0.2
Our results suggest that HYPB HMTase may coordinate histone methylation and transcriptional regulation in mammals and open perspective for the further study of the potential roles of HYPB protein in hematopoiesis and pathogenesis of HD.
SIGNOR-269071
Q96KS0
Q969H0
0
ubiquitination
down-regulates quantity by destabilization
0.349
Mechanistically, we further show that FBW7, an E3 ligase complex component that is frequently downregulated in TNBC, negatively regulates EglN2 protein stability.
SIGNOR-261997
Q8WZ74
Q14247
2
binding
up-regulates activity
0.511
Fluorescence recovery after photobleaching further suggested that CTTNBP2 modulates the mobility of cortactin in neurons. CTTNBP2 may thus help to immobilize cortactin in dendritic spines and control the density of dendritic spines.
SIGNOR-269703
P04626
P43378
0
dephosphorylation
down-regulates activity
0.304
Conversely, increasing expression of PTPN9 wild type (WT) inhibits tyrosyl phosphorylation of ErbB2 and EGFR.|Protein-tyrosine phosphatase PTPN9 negatively regulates ErbB2 and epidermal growth factor receptor signaling in breast cancer cells.
SIGNOR-277170
P27361
Q07889
1
phosphorylation
down-regulates
0.636
For example, inactivation of sos through phosphorylation by the downstream mapk
SIGNOR-26338
O00444
Q9HC77
1
phosphorylation
up-regulates
0.799
Plk2 phosphorylates the s589 and s595 residues of cpap in vitro and in vivo. This phosphorylation is critical for procentriole formation during the centrosome cycle. Plk4 also phosphorylates s595 of cpap
SIGNOR-166007
Q96BR1
Q13045
1
phosphorylation
up-regulates
0.355
Here we show that flii is an in vivo substrate of cisk that functions downstream of pi 3-kinase. Cisk can associate with flii and phosphorylate flii at residues ser(436) and thr(818).We demonstrate here that cisk can enhance er transcription, which is dependent on its kinase activity, and mutation of cisk phosphorylati...
SIGNOR-184688
Q8IZL9
Q15910
1
phosphorylation
up-regulates activity
0.2
In addition to the transcriptional feedback loop, we also identified a feed-forward loop in which CCRK induces EZH2 phosphorylation, thereby promoting p-EZH2 Ser21 -AR physical interaction for CCRK promoter co-occupancy and transcriptional activation.
SIGNOR-279017
P01100
P59595
0
transcriptional regulation
up-regulates quantity by expression
0.2
The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well
SIGNOR-260726
P38936
Q9Y463
0
phosphorylation
up-regulates activity
0.258
Mirk exerts its anti-apoptotic effects during muscle differentiation at least in part through effects on the cell cycle inhibitor and pro-survival molecule p21cip1. Overexpression and rna interference experiments demonstrated that mirk phosphorylates p21 within its nuclear localization domain at ser-153 causing a porti...
SIGNOR-235635
Q9UNZ2
P06493
0
phosphorylation
down-regulates activity
0.325
Now, we have found that p47, which mainly localizes to the nucleus during interphase, is phosphorylated on serine-140 by cdc2 at mitosis. The phosphorylated p47 does not bind to golgi membranes.
SIGNOR-102350
Q9NQX3
O43307
2
binding
up-regulates activity
0.604
Gephyrin is believed to act as a scaffold at inhibitory synapses, in a manner analogous to that of the prototypic excitatory synaptic scaffold, PSD-95. The best-known function of gephyrin is to bring the inhibitory synaptic receptors and to stabilize them at the inhibitory synapses. gephyrin interacts with NL-2 and col...
SIGNOR-264973
P06213
P06213
2
phosphorylation
up-regulates activity
0.2
We identified the major autophosphorylation sites in the insulin receptor and correlated their phosphorylation with the phosphotransferase activity of the receptor on synthetic peptides. We conclude that 1) autophosphorylation of the insulin receptor begins by phosphorylation of Tyr-1146 and either Tyr-1150 or Tyr-1151...
SIGNOR-106510
P51608
P46531
1
transcriptional regulation
down-regulates quantity by repression
0.29
As the first step to reveal how MeCP2 phosphorylation may regulate Notch signaling, we conducted chromatin immunoprecipitation (ChIP) experiment to determine whether the phosphor-mutant MeCP2 protein has altered promoter occupancy at the promoters of Dll1 and Notch1. We found increased binding of the phosphor-mutant pr...
SIGNOR-264675
Q13148
Q9UPY3
1
post transcriptional regulation
up-regulates quantity
0.374
Molecularly, we observed that TBPH regulates the expression levels of Dicer-2 by direct protein-mRNA interactions in vivo.|In agreement with this idea, we found that the suppression of TDP-43 induces the downregulation of Dicer in human neuroblastoma cell lines signifying that the TDP-43 function is required to prevent...
SIGNOR-262114
Q9C026
P62837
2
binding
up-regulates activity
0.425
Collectively, these results indicated that TRIM9 is an E3 ligase for its self-ubiquitination and that the ubiquitination of TRIM9 likely serves as a signal for proteasomal degradation. As shown in Fig. 1A, TRIM9 was ubiquitinated by itself when incubated with UbcH5b. In contrast, ubiquitination was observed when incuba...
SIGNOR-271420
P23470
P16234
1
dephosphorylation
up-regulates activity
0.249
PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and V...
SIGNOR-254714
Q13554
Q9H6L5
1
phosphorylation
up-regulates activity
0.2
Under ER-stress conditions, activated CAMK2B phosphorylates the reticulon-homology domain of FAM134B, which enhances FAM134B oligomerization and activity in membrane fragmentation to accommodate high demand for ER-phagy. 
SIGNOR-273554
P38405
P43088
2
binding
up-regulates activity
0.25
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signali...
SIGNOR-256953
O15105
P62136
2
binding
up-regulates
0.429
Smad7, induced by alk1 activation, recruits pp1? To alk1 and thereby inhibits tgf-?/Alk1-induced smad1/5 phosphorylation in ecs
SIGNOR-145389
P17252
P43405
0
phosphorylation
up-regulates activity
0.391
We present evidence that Tyr-662 and Tyr-658 of PKCbetaI and PKCalpha, respectively, are phosphorylated by Syk in the membrane compartment of FcepsilonRI-stimulated mast cells. These phosphorylations require prior PKC autophosphorylation of the adjacent serine residues (Ser-661 and Ser-657, respectively) and generate a...
SIGNOR-246581
Q06330
O14641
2
binding
down-regulates activity
0.269
Mechanistically, Dishevelled binds and directly inhibits CSL transcription factors downstream of Notch receptors, reducing their activity. Furthermore, our data suggest that this crosstalk mechanism is conserved between vertebrate and invertebrate homologues. Thus, we identify a dual function for Dishevelled as an inhi...
SIGNOR-243999
Q8NEV1
Q99250
1
phosphorylation
up-regulates activity
0.2
We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction wit...
SIGNOR-275755
Q13547
P00519
0
phosphorylation
up-regulates activity
0.507
Despite the fact that HDAC1 was phosphorylated by co-expression with c-Abl, stabilization of HDAC1 by c-Abl was not affected by mutations in its sites phosphorylated by c-Abl.|c-Abl induces stabilization of histone deacetylase 1 (HDAC1) in a kinase activity dependent manner.
SIGNOR-280169
Q05513
P10636-2
1
phosphorylation
down-regulates activity
0.268
We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates so...
SIGNOR-275447
Q12756
P0DP24
2
binding
up-regulates activity
0.261
To better understand how KIF1A-driven dense core vesicle (DCV) transport is regulated, we identified the KIF1A interactome and focused on three binding partners, the calcium binding protein calmodulin (CaM) and two synaptic scaffolding proteins: liprin-α and TANC2. We showed that calcium, acting via CaM, enhances KIF1A...
SIGNOR-266889
P52272
Q99459
2
binding
up-regulates activity
0.635
hnRNP-M interacts directly with CDC5L and PLRG1 in vivo. we investigated whether the function of hnRNP-M in alternative splicing was affected by the central region mapped as essential for binding to the CDC5L/PLRG1 proteins. We conclude that loss of the CDC5L/PLRG1 interaction domain in hnRNP-M correlates with a loss ...
SIGNOR-239410
P08047
P28482
0
phosphorylation
up-regulates
0.644
Here we show that p42/p44 mapk directly phosphorylates sp1 on threonines 453 and 739 both in vitro and in vivo. Mutation of these sites to alanines decreases by half the mapk-dependent transcriptional activity of sp1. Phosphorylated extracellular signal-regulated protein kinases 1 and 2 phosphorylate sp1 on serine 59 a...
SIGNOR-116158
Q2T9J0
Q2T9J0
2
cleavage
down-regulates activity
0.2
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-261053
Q92993
P35790
1
acetylation
up-regulates activity
0.2
Glucose deprivation induces the binding of choline kinase α2 (CHKα2) to lipid droplets, followed by a continuous PTMs to promote lipolysis of lipid droplets, which are in turn mediated by AMPK-dependent CHKα2 Serine 279 phosphorylation and KAT5-dependent CHKα2 Lysine 247 acetylation.
SIGNOR-267648
P42574
P25963
1
cleavage
up-regulates quantity by stabilization
0.422
The cell-death protease cpp32 (caspase-3) in vitro specifically cleaved chicken and human ikappab-alpha at a conserved asp-ser sequence.Therefore, cleavage of I_B-_ by a CPP32-like protease could create what is sometimes called a super-repressor form of I_B-_ (20). That is, cleavage by CPP32 would block the ability of ...
SIGNOR-51936
P17612
Q00613
1
phosphorylation
up-regulates
0.314
Protein kinase a binds and activates heat shock factor 1hsf1 binds avidly to the catalytic subunit of pka, (pkac_) and becomes phosphorylated on a novel serine phosphorylation site within its central regulatory domain (serine 320 or s320), both in vitro and in vivo. Intracellular pkac_ levels and phosphorylation of hsf...
SIGNOR-169853
P56279
P31751
2
binding
up-regulates
0.547
Full-length tcl1 and its isoforms bind to akt / in in vitro kinase assays using gsk-3_ as a substrate, we found that the presence of any of the tcl1 family proteins (tcl1, mtcp1, or tcl1b) as gst fusion proteins significantly enhanced akt-induced gsk-3_ phosphorylation
SIGNOR-81683
Q13485
P01106
1
transcriptional regulation
down-regulates quantity by repression
0.64
Down-regulation of c-Myc is a critical event for growth inhibition induced by transforming growth factor-β (TGF-β) and is frequently impaired in cancer cells. We determined a Smad-responsive element in the c-mycpromoter.
SIGNOR-251493
Q15077
Q03113
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- signali...
SIGNOR-257343
Q13131
Q9NP71
1
phosphorylation
down-regulates
0.451
Ampk has also been suggested to phosphorylate the glucose-sensitive transcription factor chrebpthe dna binding activity, as assayed in a gel-shift assay of the truncated chrebp, was gradually inactivated with time by treatment with ampk
SIGNOR-176494
P23786
Q86TM6
0
ubiquitination
down-regulates quantity
0.2
Taken together, these data suggest that HRD1 selectively and specifically downregulates intracellular CPT2 levels.|These results demonstrate that HRD1 ubiquitinates CPT2, which is processed through Lys-48-linked ubiquitin chains.
SIGNOR-278723
P42574
P49768
1
cleavage
up-regulates activity
0.454
Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were...
SIGNOR-261756
Q92835
P07948
0
phosphorylation
up-regulates activity
0.509
In this line, Lyn has been demonstrated to tyrosine-phosphorylate and activate SHIP1, thereby constituting a negative feedback control of PI3K-mediated signals.
SIGNOR-279060
Q9HCM2
Q13214
2
binding
up-regulates activity
0.65
We provide evidence suggesting that, in endothelial cells and glioblastoma cells, plexin-A4 is a required component of both Sema3A and Sema3B receptor complexes and inhibition of its expression nullifies both Sema3A and Sema3B signaling. The specificity for Sema3A or Sema3B is determined by the presence of plexin-A1 in...
SIGNOR-261810
Q07812
O43464
1
relocalization
up-regulates
0.313
Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi
SIGNOR-88590
P30281
Q9UKC9
2
binding
down-regulates quantity by destabilization
0.484
Here, we show that a relatively new E3 ligase component belonging to the SCF (Skip-Cullin1-F-box protein) E3 ligase family, SCF (FBXL2) , impairs cell proliferation by mediating cyclin D3 polyubiquitination and degradation. 
SIGNOR-271887
O14965
Q96EZ8
1
phosphorylation
up-regulates activity
0.316
We conclude that Aurora-A phosphorylates MCRS1 on Ser35/36 specifically during mitosis.
SIGNOR-278232
O94856
Q01484
1
relocalization
up-regulates quantity
0.694
Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with...
SIGNOR-266716
Q9Y5G8
Q9Y5H9
2
binding
up-regulates activity
0.2
The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.
SIGNOR-265695
P67809
Q7Z6E9
0
ubiquitination
down-regulates quantity by destabilization
0.317
RBBP6 interacts with multifunctional protein YB-1 through its RING finger domain, leading to ubiquitination and proteosomal degradation of YB-1
SIGNOR-271773
Q14247
P11362
0
phosphorylation
down-regulates
0.313
Cortactin, which is an actin-binding protein that also plays a role in actin cytoskeleton dynamics (45), was phosphorylated on tyr-446 in our assay (by fgfr1).Phosphorylation of these residues attenuates the f-actin cross-linking activity
SIGNOR-98618
P61077
Q8NEG5
2
binding
up-regulates activity
0.331
MEX can act as an E3, Ub (ubiquitin) ligase, through the E2, Ub-conjugating enzymes UbcH5a, UbcH5c or UbcH6. A region of MEX that contains the RING fingers and the ZZ zinc finger was required for interaction with UbcH5a and MEX self-association, whereas the SWIM domain was critical for MEX ubiquitination. The expressio...
SIGNOR-271557
P17612
Q9P0L9
1
phosphorylation
up-regulates activity
0.2
PKD2L1 channel activation by PKA phosphorylation. In this study, we observed the activity of PKD2L1 channel increased by the downstream cascades of β2AR and found the clustered phosphorylation sites, Ser-682, Ser-685, and Ser-686 that are significant in the channel regulation by phosphorylation.
SIGNOR-273562
P55212
P49768
1
cleavage
up-regulates activity
0.372
Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were...
SIGNOR-261753
P35222
Q05655
0
phosphorylation
down-regulates activity
0.269
Moreover, protein kinase Cδ, which directly phosphorylates β-catenin at Ser715, is required for the TRIM33–β-catenin interaction. | Phosphorylation of β-catenin Ser715 is critical for TRIM33-induced β-catenin degradation
SIGNOR-260897
Q14344
P43657
2
binding
up-regulates activity
0.353
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- signali...
SIGNOR-257347
Q13492
P53675
2
binding
up-regulates
0.729
Calm interacts with the clathrin heavy chain through its c-terminal third and with phophoinositides through its ap180 n-terminal homology (anth) domain, promoting assembly of clathrin triskelia into clathrin cagesin vitro
SIGNOR-144733
P53778
Q12888
1
phosphorylation
down-regulates activity
0.2
Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks |phosphorylation of T1609 is likely to be mediated by p38 MAPK
SIGNOR-264448
P45985
P31749
0
phosphorylation
down-regulates
0.594
Akt phosphorylated sek1 on serine 78.
SIGNOR-236494
O60610
O14757
0
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
P06702
O00206
2
binding
up-regulates activity
0.546
RAGE and TLR4 are well-characterized S100A8 and S100A9 receptors and expressed in AML cells. S100A9 binds to TLR4 and induces signaling pathways,promoting leukemic cell differentiation and proliferation arrest. Binding of S100A9 to TLR4 stimulates the phosphorylation of JNK, ERK1/2, and p38 MAPK, which leads to the a...
SIGNOR-261918
Q9HB09
P49841
0
phosphorylation
up-regulates
0.338
Gsk3b phosphorylates bcl2l12 at s156. Ectopic expression of gfp-fused bcl2l12 or bcl2l12a in u87mg cells leads to repression of apoptotic markers and protects against staurosporine (sts) insults, indicating an antiapoptotic role for both bcl2l12 and bcl2l12a. In contrast, no anti-apoptotic ability was seen in bcl2l12(s...
SIGNOR-195512
P11168
P52945
0
transcriptional regulation
up-regulates quantity by expression
0.522
In conclusion, Pdx1 confers the expression of pancreatic β-cell-specific genes, such as genes encoding insulin, islet amyloid polypeptide, Glut2, and Nkx6.1.
SIGNOR-255540
P17612
P35240
1
phosphorylation
up-regulates
0.405
Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell grow...
SIGNOR-159840
Q02535
Q14289
0
phosphorylation
up-regulates quantity
0.2
Taken together these findings demonstrated that Pyk2 mediates the expression of ID3 protein.|Together these findings from the combined MS+MS/MS data confirm that Flag tagged ID3 is phosphorylated by active recombinant Pyk2 kinase; and support the phospho-Tyr band that was detected at the corresponding MW ~ 13 kDA for F...
SIGNOR-278496
Q02156
O60716
1
phosphorylation
down-regulates
0.2
We find that ctnnd1/p120ctn phosphorylation at serine 268 (p-s268) occurs in a strictly pkc_-dependent manner,serine/threonine phosphorylation of p120-ctn has been reported to affect the integrity of ajs [12], [24] and [25]. Xia et al. (2003) reported that several residues (ser122, ser252, ser268, ser288, thr310, ser31...
SIGNOR-201600
P41146
O95837
2
binding
up-regulates activity
0.353
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- signali...
SIGNOR-257209
P46531
Q92993
0
acetylation
down-regulates
0.414
This result implies that the residues k2019, k2039, k2044, and k2068 of notch1-ic are the major targets of the acetyltransferase activity of tip60.
SIGNOR-156923
Q9BXM7
Q9Y2N7
1
phosphorylation
down-regulates activity
0.347
Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ub...
SIGNOR-263090
Q70Z35
P60484
2
binding
down-regulates activity
0.62
Here, we report that P-REX2 interacts with PTEN via two interfaces. In summary, P-REX2 docks to the PDZ-BD of PTEN through its C-terminal domain, reads the phosphorylation state of the PTEN tail via the DH domain, and inhibits PTEN activity by unleashing the PH domain
SIGNOR-259189
P35568
P29376
0
phosphorylation
up-regulates
0.314
Recently, we demonstrated that ltk utilizes shc and irs-1 as two major substrates and while both equally activate the ras pathway, only irs-1 suppresses apoptosis of hematopoietic cells.
SIGNOR-49531