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P46060
O75592
1
relocalization
down-regulates quantity by destabilization
0.315
SUMOylated RanGAP1 Inhibits MYCBP2 Activity and Mediates Its Transport to the Nucleus. Surprisingly, we did not find MYCBP2-dependent ubiquitylation of SUMOylated RanGAP1 but instead a strong inhibition of the ubiquitin ligase activity of MYCBP2 in the presence of SUMOylated RanGAP1, as determined by the presence of ubiquitylated proteins. this effect was specific for SUMOylated RanGAP1, because the unmodified form of RanGAP1 did not affect MYCBP2-dependent protein ubiquitylation. , SUMOylated RanGAP1 inhibited the ubiquitin ligase activity of MYCBP2, and it is tempting to speculate that SUMOylated RanGAP1 inhibits the ubiquitin ligase activity of MYCBP2 to ensure MYCBP2 silencing during its transport to the nucleus
SIGNOR-261203
Q15831
P27448
1
phosphorylation
up-regulates activity
0.315
Regulation of the wnt signalling component par1a by the peutz-jeghers syndrome kinase lkb1. Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1. Mark3 is activated by phosphorylation on thr-211.
SIGNOR-104059
P00441
O75460
1
binding
up-regulates activity
0.315
SOD1mut-induced ER stress |we first examined whether SOD1mut induces ER stress in NSC34 motor neurons, as assessed by band-shift analyses of the ER transmembrane kinase receptors IRE1 and PERK. Adenovirus (Ad)-mediated expression of ALS-linked SOD1mut (SOD1G93A) was detectable within 48 h of infection (Supplemental Fig. S1A). SOD1mut (SOD1A4V, SOD1G85R, and SOD1G93A) but not wild-type SOD1 (SOD1wt) activated IRE1 and PERK
SIGNOR-262786
Q13627
P98177
1
phosphorylation
down-regulates
0.315
Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity
SIGNOR-183677
Q9HC98
P52948
1
phosphorylation
down-regulates activity
0.315
To elucidate which of the identified sites can be targeted by CDK1/cyclin B1 and Nek6 in vitro (Figure S1D), we performed phosphorylation reactions using recombinant kinases and unlabeled ATP followed by phosphopeptide mapping (Table S1). MS analysis confirmed phosphorylation of S591 and S822 by Nek6 as well as phosphorylation of T529, T536, S595, S606, and T653 by CDK1. Phosphomimetic Mutants of Nup98 Show Defects in NPC Localization
SIGNOR-273893
P19784
Q99801
1
phosphorylation
up-regulates
0.315
In vitro kinase assays followed by mass spectrometric analyses demonstrated that ck2 phosphorylated recombinant nkx3.1 on thr89 and thr93. We have also determined that nkx3.1 is degraded primarily through a proteasomal pathway, suggesting that phosphorylation by ck2 protects nkx3.1 from degradation.
SIGNOR-145501
Q15418
Q05195
1
phosphorylation
down-regulates
0.315
In this study, we showed that mad1 is a substrate of p90 ribosomal kinase (rsk) and p70 s6 kinase (s6k). Both rsk and s6k phosphorylate serine 145 of mad1 upon serum or insulin stimulation. Ser-145 phosphorylation of mad1 accelerates the ubiquitination and degradation of mad1 through the 26s proteasome pathway
SIGNOR-178586
O14757
A0AVK6
1
phosphorylation
down-regulates activity
0.315
Chk1 inhibits the transcriptional repressor function of E2F7 and E2F8 to promote cell cycle progression and prevent apoptosis.|Here, we demonstrate that Chk1 phosphorylates both E2F7 and E2F8 in response to DNA damage.
SIGNOR-279693
P04150
P49716
1
transcriptional regulation
up-regulates quantity
0.315
We conclude that glucocorticoid-induced adipogenesis from bone marrow stromal cells is mediated through a reaction cascade in which dexamethasone transcriptionally activates C/EBPδ; C/EBPδ then binds to PPARγ2 promoter and transactivates PPARγ2 gene expression.
SIGNOR-253061
Q14790
Q96EP0
1
cleavage
down-regulates activity
0.315
We show that LUBAC interacted with caspase-1 via HOIP and modified its CARD domain with linear polyubiquitin and that depletion of HOIP or Sharpin resulted in heightened caspase-1 activation and cell death in response to inflammasome activation, unlike what is observed in macrophages. Reciprocally, caspase-1, as well as caspase-8, regulated LUBAC activity by proteolytically processing HOIP at Asp-348 and Asp-387 during the execution of cell death.
SIGNOR-272194
P35462
P19086
1
binding
up-regulates activity
0.315
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-257097
Q13464
Q15746
1
binding
up-regulates
0.315
Rock proteins are known to regulate mlc-phosphorylation, and apoptotic cells exhibit a gradual increase in levels of phosphorylated mlc concomitant with rock i cleavage.
SIGNOR-106552
P33981
P54132
1
phosphorylation
up-regulates activity
0.315
Moreover, in mitosis, TTK promotes phosphorylation of Bloom syndrome protein (BLM) and subsequent interaction of BLM with PLK1, ensuring accurate chromosome segregation xref .|Moreover, in mitosis, TTK promotes phosphorylation of Bloom syndrome protein and subsequent interaction of Bloom syndrome protein with PLK1, ensuring accurate chromosome segregation .
SIGNOR-280156
Q7KZI7
Q8IVT5
1
phosphorylation
down-regulates activity
0.315
In vivo, MARK2 appears to negatively regulate KSR1 in insulin sensitivity.|These data suggest that MARK2 phosphorylates KSR1 on Ser392, which has been shown previously to function as a negative regulatory site xref .
SIGNOR-279343
O94921
P37802
1
phosphorylation
down-regulates activity
0.315
This newly identified oncogene–tumor suppressor cascade, where oncogenic PFTK1 inactivates a tumor suppressor gene TAGLN2 via phosphorylation|. Our data therefore underline much importance for S83 and S163 residues on TAGLN2 in its actin-binding capacity.
SIGNOR-265103
P29274
P38405
1
binding
up-regulates activity
0.315
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-256909
Q9H159
P35222
1
binding
up-regulates activity
0.315
At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin
SIGNOR-265858
Q99704
P05556
1
binding
down-regulates activity
0.315
Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation
SIGNOR-257669
P07550
O95837
1
binding
up-regulates activity
0.314
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-257192
P07339
P02818
1
cleavage
down-regulates quantity by destabilization
0.314
This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42.
SIGNOR-256319
Q8N6T7
P01375
1
deacetylation
up-regulates
0.314
Sirt6 regulates tnf-alfa secretion through hydrolysis of long-chain fatty acyl lysine
SIGNOR-201662
P29376
P35568
1
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
P43378
P10912
1
dephosphorylation
down-regulates activity
0.314
Protein tyrosine phosphatases (PTPs) play key roles in switching off tyrosine phosphorylation cascades, such as initiated by cytokine receptors. We have used substrate-trapping mutants of a large set of PTPs to identify members of the PTP family that have substrate specificity for the phosphorylated human GH receptor (GHR) intracellular domain. Among 31 PTPs tested, T cell (TC)-PTP, PTP-beta, PTP1B, stomach cancer-associated PTP 1 (SAP-1), Pyst-2, Meg-2, and PTP-H1 showed specificity for phosphorylated GHR
SIGNOR-248505
Q16665
P13674
1
transcriptional regulation
up-regulates quantity by expression
0.314
Hypoxia upregulates P4HA1 expression in PDAC PDOs through HIF1α. Our results show that the treatment of PDO4 and PDO11 cells with 10 μmol/L of PX-478 for 24 hours reduced the levels of P4HA1 in hypoxia (Fig. 2F), suggesting P4HA1 expression in hypoxia is regulated by HIF1α expression.
SIGNOR-279840
Q96QT4
O00418
1
phosphorylation
up-regulates activity
0.314
TRPM7 interacts with, and phosphorylates mouse eEF2-k at serine site 77
SIGNOR-277923
O14757
P53350
1
phosphorylation
down-regulates activity
0.314
 Chk1 directly phosphorylates Plk1 to disturb its interaction with Sgo1. 
SIGNOR-277914
P62136
P04637
1
dephosphorylation
down-regulates activity
0.314
Protein serine/threonine phosphatase-1 dephosphorylates p53 at Ser-15 and Ser-37 to modulate its transcriptional and apoptotic activities|In addition, our results reveal that one of the molecular mechanisms by which PP-1 promotes cell survival is to dephosphorylate p53, and thus negatively regulate p53-dependent death pathway.
SIGNOR-248557
P55317
O00712
1
binding
up-regulates
0.314
Androgen receptor (ar) action throughout prostate development and in maintenance of the prostatic epithelium is partly controlled by interactions between ar and forkhead box (fox) transcription factors, particularly foxa1./ Foxa1 is capable of bringing ar and nfix into proximity, indicating that foxa1 facilitates the ar and nfi interaction by bridging the complex.
SIGNOR-205027
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 hsf1 at s320 were both required for hsf1 to be localized to the nucleus, bind to response elements in the promoter of an hsf1 target gene
SIGNOR-169853
Q13464
O00429
1
phosphorylation
up-regulates activity
0.314
We have also previously reported that ROCK1-mediated Drp1S600 phosphorylation resulted in enhanced mitochondrial fission in podocytes
SIGNOR-262549
Q13418
O14950
1
phosphorylation
up-regulates activity
0.314
Integrin-linked kinase cdna was cloned, sequenced, expressed in e. coli, and shown to phosphorylate myosin light chain in the absence of ca(2+) at ser(19) and thr(18). Smooth muscle contraction follows an increase in cytosolic Ca(2+) concentration, activation of myosin light chain kinase, and phosphorylation of the 20-kDa light chain of myosin at Ser(19).Smooth muscle contraction follows an increase in cytosolic Ca(2+) concentration, activa
SIGNOR-106427
Q13480
A7KAX9
1
relocalization
up-regulates
0.314
Gc-gap, a rho family gtpase-activating protein that interacts with signaling adapters gab1 and gab2.
SIGNOR-102586
P17612
Q00536
1
phosphorylation
down-regulates
0.314
Here, we report that cdk16 is activated by membrane-associated cyclin y (ccny). Treatment of transfected human cells with the protein kinase a (pka) activator forskolin blocked, while kinase inhibition promoted, ccny-dependent targeting of cdk16-green fluorescent protein (gfp) to the cell membrane. Ccny binding to cdk16 required a region upstream of the kinase domain and was found to be inhibited by phosphorylation of serine 153, a potential pka phosphorylation site.
SIGNOR-191623
Q15643
P10828
1
binding
up-regulates
0.314
Trip230 binds to rb independently of thyroid hormone while it forms a complex with tr in a thyroid hormone-dependent manner. Ectopic expression of the protein trip230 in cells, but not a mutant form that does not bind to tr, enhances specifically tr-dependent transcriptional activity.
SIGNOR-50421
P12931
Q14653
1
phosphorylation
up-regulates activity
0.314
Mechanistically, the progesterone-PGR axis activates SRC, which then mediates phosphorylation of IRF3 at Y107.|Taken together, these results suggest that P4 induces PGR-dependent activation of SRC, which promotes virus-triggered activation of IRF3 as well as induction of downstream antiviral genes.In the above experiments, we noticed that SeV-induced phosphorylation of IRF3S386 but not phosphorylation of TBK1S172 (p-TBK1S172, a hallmark for TBK1 activation) was increased by P4 treatment (Fig. 4g) or decreased by knockout of PGR (Fig. 4h).
SIGNOR-279118
P06493
P27361-3
1
phosphorylation
up-regulates activity
0.314
 We found that CDK1 phosphorylates Ser343 of ERK1c, thereby allowing the binding of phosphorylated ERK1c to a complex that consists of PI4KIIIβ (also known as PI4KB) and the 14-3-3γ dimer (encoded by YWHAB). 
SIGNOR-277185
Q05655
Q9Y2R2
1
phosphorylation
down-regulates
0.314
We show that lyp is phosphorylated exclusively at ser-35 by pkc both in vitro and in vivo. our data establish a mechanism by which pkc could attenuate the cellular function of lyp, thereby augmenting t cell activation.
SIGNOR-159591
P49335
P20264
1
binding
up-regulates activity
0.314
POU proteins (Brain-1, Brain-2, Brain-4 and SCIP) serve as transcriptional transactivators. if they were to form homomeric and heteromeric complexes with each other, depending on the particular combination, they might have different DNA-binding specificities and, thus, activate different genes.
SIGNOR-220127
Q13901
P20393
1
binding
up-regulates activity
0.314
SUN-CoR is a protein involved in transcriptional repression by nuclear hormone receptors. The C terminus of SUN-CoR interacts with TR and RevErb in vitro and associates with RevErb in cells, SUN-CoR potentiates repression by both receptors in cells, and the N terminus of SUN-CoR contains an intrinsic repression domain.
SIGNOR-241272
Q13618
Q9Y4X5
1
binding
up-regulates activity
0.314
Here, we provide evidence that Ariadne RBR E3 ubiquitin ligases such as TRIAD1 and HHARI can bind and be activated by CRL complexes. Whereas TRIAD1 specifically associates with CUL5–RBX2, HHARI is more promiscuous towards cullin types and associates with RBX1-associated cullins 1, 2, 3, and 4A. Interestingly, both TRIAD1 and HHARI show a strong preference for binding the neddylated form of the cullin. Our data suggest a novel function of NEDD8 in directing specific CRLs to Ariadne RBR ligases, which in turn exert influence on the levels of their cognate neddylated cullin.
SIGNOR-268846
P67775
Q14653
1
dephosphorylation
down-regulates activity
0.314
RACK1 Negatively Regulates the Type I IFN pathway. Here we report that IRF3 is deactivated via dephosphorylation mediated by the serine and threonine phosphatase PP2A and its adaptor protein RACK1. The PP2A-RACK1 complex negatively regulated the IRF3 pathway after LPS or poly(I:C) stimulation or Sendai virus (SeV) infection.
SIGNOR-260944
Q16539
O43257
1
phosphorylation
up-regulates
0.314
We show that the srcap subunit named znhit1 or p18(hamlet), which is a substrate of p38 mapk, is recruited to the myogenin promoter at the onset of muscle differentiation, in a p38 mapk-dependent manner. Furthermore, p18hamlet was phosphorylated during myoblast differentiation in a p38 mapk-dependent manner (dal testo pmc)
SIGNOR-165571
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
P36406
Q9Y4K3
1
ubiquitination
up-regulates activity
0.313
We show here that the upregulation of NF-kappaB by UL144 is dependent upon cellular tripartite motif 23 (TRIM23) protein. We propose a mechanism by which UL144 activates NF-kappaB through a direct interaction with the cellular protein TRIM23 in a complex containing TRAF6. we propose that TRIM23 mediates TRAF6 autoubiquitination in the presence of UL144, resulting in the virally controlled activation of NF-κB stimulation at early times of HCMV infection.
SIGNOR-266655
Q8NBI6
P46531
1
binding
up-regulates
0.313
Xxylt1 acts on the xyl1,3glc-o-linked glycan of notch egf domains.
SIGNOR-177745
P00519
Q6NUN9
1
phosphorylation
up-regulates activity
0.313
C-Abl-mediated phosphorylation of PARIS at Y137 (within the Krüppel-associated box domain) drives its association with KAP1 and the repression of genes with diverse functions in pathways such as chromatin remodelling and p53-dependent cell death.
SIGNOR-277626
Q16816
P10636
1
phosphorylation
down-regulates activity
0.313
Muscle phosphorylase kinase phosphorylates Ser237, Ser262, Ser285, Ser305, and Ser352 of human tau. in vitro phosphorylation of tau on Ser262 alone strongly reduced the ability of tau to bind microtubules whereas the phosphorylation of many Ser/Thr-Pro motif sites of tau showed moderate effects on the binding of tau to microtubules
SIGNOR-250285
P27361
O75581
1
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
P03951
P14210
1
cleavage
up-regulates activity
0.313
the ability of plasma kallikrein and FXIa to activate pro-HGF in vitro raises the possibility that mediators of inflammation and blood coagulation may also regulate processes that involve the HGF/c-Met pathway, such as tissue repair and angiogenesis.Unlike other known activators, both FXIa and kallikrein processed pro-HGF by cleavage at two sites. Using N-terminal sequencing they were identified as the normal cleavage site Arg(494)-Val(495) and the novel site Arg(424)-His(425) located in the K4 domain of the alpha-chain.
SIGNOR-256515
P30304
Q12778
1
dephosphorylation
up-regulates activity
0.313
In this study, we revealed that Cdc25A enhances Foxo1 stability by dephosphorylating Cdk2, and Foxo1 was shown to directly regulate transcription of the metastatic factor MMP1.
SIGNOR-277139
Q9UHC7
P38936
1
polyubiquitination
down-regulates quantity by destabilization
0.313
Makorin Ring Finger Protein 1 (MKRN1) is a transcriptional co-regulator and an E3 ligase. Here, we show that MKRN1 simultaneously functions as a differentially negative regulator of p53 and p21. In normal conditions, MKRN1 could destabilize both p53 and p21 through ubiquitination and proteasome-dependent degradation. As a result, depletion of MKRN1 induced growth arrest through activation of p53 and p21. 
SIGNOR-271845
P45452
P00748
1
cleavage
down-regulates quantity by destabilization
0.313
The data presented in this study show for the first time the degradation of Factor XII of the blood clotting system by matrix metalloproteinases. MMP-12, MMP-13, and MMP-14 cleave at Gly376Leu377|However, no activity of Factor XII can be observed after MMPinduced cleavage.
SIGNOR-263609
P55072
O14965
1
binding
down-regulates activity
0.313
The UBXN-2/p37/p47 adaptors of CDC-48/p97 regulate mitosis by limiting the centrosomal recruitment of Aurora A.|We found that UBXN-2 and CDC-48 coimmunoprecipitated with AIR-1 from embryonic extracts
SIGNOR-265044
Q16829
P10912
1
dephosphorylation
down-regulates
0.313
Identification of protein tyrosine phosphatases with specificity for the ligand-activated growth hormone receptor.
SIGNOR-104545
Q12840
P78352
1
binding
up-regulates activity
0.313
Postsynaptic density protein 95 (PSD-95) is transported by KIF5 to dendritic regions
SIGNOR-264065
O14713
P05107
1
binding
down-regulates activity
0.313
Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation
SIGNOR-257649
P41145
P19086
1
binding
up-regulates activity
0.313
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-257105
P11362
Q14247
1
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
P20823
Q12864
1
transcriptional regulation
up-regulates quantity by expression
0.313
The present study aims to identify the transcription factors which interact and regulate CDH17 promoter activity that might contribute to the up-regulation of CDH17 gene in human HCC|we identified hepatic nuclear factor 1α (HNF1α) and caudal-related homeobox 2 (CDX2) binding sites at the proximal promoter region which modulate the CDH17 promoter activities in two HCC cell lines (Hep3B and MHCC97L)
SIGNOR-253970
P43250
Q01726
1
phosphorylation
down-regulates activity
0.313
Overexpression of GRK6 Inhibits Agonist-Induced cAMP Production in HBL Human Melanoma Cells, without Affecting MC1R Gene Expression
SIGNOR-252389
P49841
P30304
1
phosphorylation
down-regulates quantity by repression
0.313
Here, we report that casein kinase 1 alpha (ck1alpha) phosphorylates cdc25a on both s79 and s82 in a hierarchical manner requiring prior phosphorylation of s76 by chk1 or gsk-3beta. This facilitates beta-trcp binding and ubiquitin-mediated proteolysis of cdc25a
SIGNOR-164742
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
O14713
P26012
1
binding
down-regulates activity
0.313
Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation
SIGNOR-257667
Q6UXX9
Q9ULV1
1
ubiquitination
down-regulates quantity
0.313
Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6.
SIGNOR-260117
Q13627
Q9NYY3
1
phosphorylation
up-regulates quantity by stabilization
0.313
 In the present study, it was demonstrated that dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) interacts with and phosphorylates PLK2 at Ser358. DYRK1A-mediated phosphorylation of PLK2 increases its protein stability. 
SIGNOR-277805
Q96SN8
Q12834
1
binding
down-regulates activity
0.313
We show here that inhibition of CDK5RAP2 expression causes chromosome mis-segregation, fails to maintain the spindle checkpoint, and is associated with reduced expression of the spindle checkpoint proteins BUBR1 and MAD2 and an increase in chromatin-associated CDC20.|We found that the APC activator CDC20, but not others we exam-ined, was present in the CDK5RAP2 immunocomplex in HeLa cell extracts (Fig. 3A). CDK5RAP2 was detected in the CDC20 immunocomplex as well (Fig. 3B).
SIGNOR-260311
Q9GZV5
Q15361
1
binding
up-regulates
0.313
Taz is a coactivator for pax8 and ttf-1, two transcription factors involved in thyroid differentiation. / we show that this interaction leads to a significant enhancement of the transcriptional activity of pax8 and ttf-1 on the thyroglobulin promoter thus suggesting a role of taz in the control of genes involved in thyroid development and differentiation.
SIGNOR-182296
Q6W2J9
O15379
1
binding
up-regulates activity
0.313
BCoR can interact w Because HDACs appear to be involved in repression by an increasing number of transcriptional repressors, we tested whether BCoR can associate with HDACs. BCoR can interact with HDAC1, HDAC3, and HDAC-B/5 more strongly than with HDAC-A/4, HDAC-C, HDAC-D, and HDAC-E.
SIGNOR-252237
P07948
Q12972
1
phosphorylation
down-regulates activity
0.312
Tyrosine phosphorylation of NIPP1 by Lyn was abolished by the Tyr-264 to Asp mutation.
SIGNOR-251405
P48729
P16220
1
phosphorylation
up-regulates
0.312
Ser108, ser111 and ser114, located in a region matching the consensus sequence for the casein kinase ii target, were required.These results strongly suggest that the casein kinase ii target region is involved in cell cycle-regulated phosphorylation of the creb protein and also in transcriptional enhancement.
SIGNOR-64258
Q02156
P28329
1
phosphorylation
up-regulates
0.312
We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation
SIGNOR-129312
P35408
P63096
1
binding
up-regulates activity
0.312
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-257032
P05154
P02751
1
binding
down-regulates activity
0.312
SERPINA5 inhibits HCC cell migration by directly interacting with fibronectin. SERPINA5 disrupts the fibronectin–integrin β1 signaling pathway.
SIGNOR-265881
P27361
O95817
1
phosphorylation
down-regulates quantity by destabilization
0.312
We further demonstrated BAG3, a HSP70 co-chaperone, is a bona fide substrate of SCFFBXO22. FBXO22 mediates BAG3 ubiquitination and degradation that requires ERK-dependent BAG3 phosphorylation at S377.
SIGNOR-277318
P27361
Q9HAV4
1
phosphorylation
down-regulates activity
0.312
Here we show that ERK suppresses pre-miRNA export from the nucleus through phosphorylation of exportin-5 (XPO5) at T345/S416/S497. After phosphorylation by ERK, conformation of XPO5 is altered by prolyl isomerase Pin1, resulting in reduction of pre-miRNA loading. 
SIGNOR-262985
P27361
O60885
1
null
down-regulates activity
0.312
The MYC stabilizing kinase, ERK1, regulates MYC levels directly and indirectly by inhibiting BRD4 kinase activity.
SIGNOR-262048
P00519
Q8TDZ2
1
phosphorylation
up-regulates activity
0.312
Biochemical assays revealed Abl phosphorylates Mical to directly amplify Mical Redox-mediated F-actin disassembly.|We now find that the Abl non receptor protein tyrosine kinase and oncoprotein signaling pathway activates Mical to direct multiple cellular effects - including extending and shaping cellular processes, guiding axons, and orchestrating cancer cell invasion, colony formation, and survival.
SIGNOR-279674
O00141
P14672
1
phosphorylation
up-regulates activity
0.312
We evaluated the putative role of sgk1 in the modulation of glut4. Coexpression of the kinase along with glut4 in xenopus oocytes stimulated glucose transport. The enhanced glut4 activity was paralleled by increased transporter abundance in the plasma membrane. Disruption of the sgk1 phosphorylation site on glut4 ((s274a)glut4) abrogated the stimulating effect of sgk1. In summary, sgk1 promotes glucose transporter membrane abundance via glut4 phosphorylation at ser274.
SIGNOR-236653
P28223
P19086
1
binding
up-regulates activity
0.312
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-257021
Q13464
P14136
1
phosphorylation
down-regulates activity
0.312
We report here that aurora-b phosphorylates gfap and desmin in vitro, and this phosphorylation leads to a reduction in filament forming ability. The sites phosphorylated by aurora-b;thr-7/ser-13/ser-38 of gfap, and thr-16 of desmin are common with those related to rho-associated kinase (rho-kinase), which has been reported to phosphorylate gfap and desmin at cleavage furrow during cytokinesis. We identified ser-59 of desmin to be a specific site phosphorylated by aurora-b in vitro.
SIGNOR-100192
Q92835
P16885
1
dephosphorylation
down-regulates activity
0.312
An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling.
SIGNOR-268455
Q13315
O43684
1
phosphorylation
up-regulates activity
0.312
Taken together, we highlight the functional significance of the crosstalk between the kinetochore-oriented signal and double-strand break repair pathways via ATM phosphorylation of Bub3 on Ser135.
SIGNOR-277582
P49841
Q01974
1
phosphorylation
down-regulates activity
0.312
We identify ror2 ser 864 as a critical residue phosphorylated by gsk3 and required for noncanonical receptor activation by wnt5a, analogous to the priming phosphorylation of low-density receptor-related protein 6 (lrp6) in response to wnt3a.
SIGNOR-169642
Q4V328
Q13233
1
binding
up-regulates activity
0.312
To examine whether GRASP‐1 interacts with MEKK1 and JNK1 in neurons, co‐immunoprecipitation experiments were performed with detergent‐solubilized extracts from cultured cortical neurons. Both antiJNK1 and anti‐MEKK1 antibodies immunoprecipitated GRASP‐1 from neuronal lysates. These results suggest that GRASP‐1 interacts with MEKK1 and JNK1 in neurons.
SIGNOR-260640
P17612
P13224
1
phosphorylation
down-regulates activity
0.312
Platelet glycoprotein Ib beta is phosphorylated on serine 166 by cyclic AMP-dependent protein kinase. phosphorylation of this residue may contribute to the inhibitory actions of cyclic AMP by inhibiting collagen-induced polymerization of actin.
SIGNOR-249986
P12931
P48048
1
phosphorylation
down-regulates
0.312
Inhibition of c-src with herbimycin a significantly decreased the tyrosine phosphorylation level of romk1... tyrosine dephosphorylation enhances the exocytosis of romk1
SIGNOR-97803
P48729
P12830
1
phosphorylation
down-regulates activity
0.312
Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts|CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846
SIGNOR-274045
P17612
P30301
1
phosphorylation
down-regulates activity
0.312
Phosphorylation at one of these sites (serine 243) could be increased by A kinase in vitro. phosphorylation of MIP reconstituted into single bilayers increased the voltage dependence and long-term closures of the channels observed.
SIGNOR-250018
P78352
Q9HCD6
1
binding
up-regulates activity
0.312
In the present study, we provide evidence that TANC1 and its close relative TANC2 regulate dendritic spines and excitatory synapses. our results indicate that TANC-dependent spine/synapse maintenance requires TANC binding to PSD-95, which promotes synaptic localization of TANC proteins. Thus, it is likely that interaction with PSD-95 concentrates TANC proteins at synapses, where they play a role in mediating PSD-95-dependent maintenance of spines and synapses.
SIGNOR-266895
Q13043
Q14457
1
phosphorylation
up-regulates activity
0.312
These results suggest that Mst1 directly stimulates interaction between Beclin1 and Bcl-2.|We here demonstrate that Mst1-induced phosphorylation of Beclin1 in its BH3 domain at Thr 108 promotes binding of Beclin1 with Bcl-2/Bcl-xL.
SIGNOR-278502
P12931
Q9NR80
1
phosphorylation
up-regulates
0.312
This observation strongly argues for the positive role of tyr94 phosphorylation in egf-induced asef activation following the activation of rac1.
SIGNOR-179601
P17612
Q9Y2K6
1
phosphorylation
down-regulates quantity by destabilization
0.311
Upon β2AR activation, a specific isoform of the second messenger cAMP-dependent protein kinase A (PKAα) rapidly phosphorylates USP20 on serine 333 located in its unique insertion domain. This phosphorylation of USP20 correlates with a characteristic SDS-PAGE mobility shift of the protein, blocks its deubiquitinase activity, promotes its dissociation from the activated β2AR complex, and facilitates trafficking of the ubiquitinated β2AR to autophagosomes, which fuse with lysosomes to form autolysosomes where receptors are degraded.
SIGNOR-273795
P28482
P24928
1
phosphorylation
down-regulates
0.311
Erk1/2 are major ser-5 kinases after h2o2 treatment. These results suggest that subsequent to h2o2 treatment, the ser-5-phosphorylated form, but not the ser-2-phosphorylated form or the unphosphorylated form, is targeted for rapid proteasomal degradation through its ubiquitination.
SIGNOR-120160
Q9GZV5
P37231
1
binding
down-regulates
0.311
Kmp also enhanced the association of taz with ppar_, thereby suppressing the gene transcription of ppar_ targets and resulting in diminished adipocyte differentiation.
SIGNOR-195215
Q05655
P28329
1
phosphorylation
up-regulates quantity
0.311
Finally, basal ChAT phosphorylation in neurons is mediated predominantly by PKC at Ser-476, with PKC activation increasing phosphorylation at Ser-440 and enhancing ChAT activity.
SIGNOR-249272
O15550
Q05516
1
transcriptional regulation
up-regulates quantity by expression
0.311
UTX catalytic activity has been reported to upregulate expression of the master transcription factor PLZF and to modulate superenhancer accessibility in invariant natural killer T cells.
SIGNOR-260038
P07948
Q14790
1
phosphorylation
down-regulates activity
0.311
The non-receptor tyrosine kinase, Lyn, can phosphorylate caspase-8 on Tyr-397 and Tyr-465, rendering it resistant to activational cleavage and inhibiting apoptosis.
SIGNOR-272980
Q4V328
P45983
1
binding
up-regulates activity
0.311
To examine whether GRASP‐1 interacts with MEKK1 and JNK1 in neurons, co‐immunoprecipitation experiments were performed with detergent‐solubilized extracts from cultured cortical neurons. Both antiJNK1 and anti‐MEKK1 antibodies immunoprecipitated GRASP‐1 from neuronal lysates. These results suggest that GRASP‐1 interacts with MEKK1 and JNK1 in neurons. GRASP-1 potently activates JNK pathway signaling, with no effect on ERK signaling. Such JNK pathway activating activity requires binding of GRASP-1 to both JNK and the upstream JNK pathway activator MEKK-1.
SIGNOR-260639
P49137
P42574
1
phosphorylation
up-regulates activity
0.311
MK2 Phosphorylates Caspase-3, Facilitates Nuclear Translocation of Caspase 3, and Regulates Apoptosis.|Over-expression of MK2 led to an increase in nuclear caspase-3 activity.
SIGNOR-278960
Q04721
Q9Y4K3
1
binding
down-regulates activity
0.311
 NOTCH2 attenuated the TRAF6-AKT signaling axis via an interaction between the NOTCH2 intracellular domain (N2ICD) and TRAF6, which inhibited epithelial-mesenchymal transition (EMT) and eventually suppressed NPC metastasis.
SIGNOR-265562