IdA
string
IdB
string
labels
int64
mechanism
string
effect
string
score
float64
sentence
string
signor_id
string
O43597
Q13627
0
phosphorylation
down-regulates
0.304
We identify dyrk1a as one of the protein kinases of sprouty2. We show that dyrk1a interacts with and regulates the phosphorylation status of sprouty2. Moreover, we identify thr75 on sprouty2 as a dyrk1a phosphorylation site in vitro and in vivo.
SIGNOR-179828
Q02156
O94925
1
phosphorylation
up-regulates activity
0.2
PKCε is the kinase that phosphorylates GAC at Ser314.
SIGNOR-277387
O75688
O14920
1
dephosphorylation
down-regulates activity
0.404
PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha-induced IKKbeta-NF-kappaB activation|Overexpression of PPM1A or PPM1B results in dephosphorylation of IKKbeta at Ser177 and Ser181 and termination of IKKbeta-induced NF-kappaB activation.
SIGNOR-248343
P15336
P28482
0
phosphorylation
up-regulates
0.733
Here, we show that in fibroblasts, insulin, epidermal growth factor (egf) and serum activate atf2 via a so far unknown two-step mechanism involving two distinct ras effector pathways: the raf-mek-erk pathway induces phosphorylation of atf2 thr71, whereas subsequent atf2 thr69 phosphorylation requires the ral-ralgds-src-p38 pathway.
SIGNOR-90517
P17252
P48050
1
phosphorylation
down-regulates activity
0.2
These results therefore indicate that Kir2.3 is directly modulated by PKC phosphorylation of its channel protein and threonine 53 is the PKC phosphorylation site in Kir2.3.
SIGNOR-275965
P30291
P63151
0
dephosphorylation
up-regulates quantity by stabilization
0.385
Knockout of FAM122A results in activation of PP2A-B55α, a phosphatase that dephosphorylates the WEE1 protein and rescues WEE1 from ubiquitin-mediated degradation. in tumor cells with oncogene-driven replication stress, CHK1 can directly phosphorylate FAM122A, leading to activation of the PP2A-B55α phosphatase and increased WEE1 expression.
SIGNOR-266381
P08581
P23470
0
dephosphorylation
down-regulates activity
0.317
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 VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.
SIGNOR-254712
Q9P0L2
P27816
1
phosphorylation
down-regulates activity
0.437
Here we show that p110mark phosphorylates analogous KXGS sites in the microtubule binding domains of the neuronal MAP2 and the ubiquitous MAP4. Phosphorylation in vitro leads to the dissociation of MAP2 and MAP4 from microtubules and to a pronounced increase in dynamic instability.
SIGNOR-250171
P56524
P12830
1
transcriptional regulation
down-regulates quantity by repression
0.287
GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells.
SIGNOR-275663
Q9NRC8
Q16695
1
deacetylation
up-regulates activity
0.2
Besides confirming the previously reported histone H3K18 deacylation activity, our results revealed that SIRT7 has an astonishingly high activity to catalyze deacylation of H3K36 and is also catalytically active to deacylate H3K37.
SIGNOR-275876
P58753
Q9NWF9
0
ubiquitination
down-regulates quantity by destabilization
0.387
Triad3A promotes proteolytic degradation of adapter proteins. A, Triad3A promotes down-regulation of TIRAP, TRIF, and RIP1 proteins.
SIGNOR-271607
O96017
Q9NQS7
1
phosphorylation
up-regulates activity
0.261
Also, inhibition of Chk2 by Chk2 inhibitor II in cytokinesis after release of cells from a nocodazole-induced prometaphase block diminished INCENP localization to the midbody center in late midbodies (Fig. 1, M and N).|In turn, active Chk2 phosphorylates human INCENP at the newly identified site Ser91 to promote INCENP binding to Mklp2, resulting in recruitment of the INCENP\u2013Mklp2 complex to the midbody center through Mklp2\u2019s interaction with the midbody protein Cep55 to delay abscission.
SIGNOR-279695
Q14790
P42574
1
cleavage
up-regulates activity
0.726
Triggering of the DISC leads to caspase-8 activation. Active caspase-8 cleaves caspase-3 which, in type I cells, leads to cell death induction.
SIGNOR-171767
Q09472
Q6DJT9
1
acetylation
up-regulates
0.308
Plag1 and plagl2 are also regulated by acetylation. They are acetylated and activated by p300 and deacetylated and repressed by hdac7.
SIGNOR-140915
P78536
P01375
1
cleavage
up-regulates quantity
0.704
We have now purified and cloned a metalloproteinase that specifically cleaves precursor TNF-alpha. [...]This enzyme (called the tnf-alpha-converting enzyme, or tace) is a new member of the family of mammalian adamalysins (or adams), for which no physiological catalytic function has previously been identified.
SIGNOR-46754
Q9NVD7
P28482
0
phosphorylation
up-regulates activity
0.259
Actopaxin (alpha-parvin) is a paxillin, integrin-linked kinase, and F-actin binding focal adhesion protein with several serine phosphorylation sites in the amino terminus that contribute to the regulation of cell spreading and migration.|Actopaxin phosphorylation of Ser4/8 enhances cell migration whereas a nonphosphorylatable (Quint) mutant suppresses migration in U2OS osteosarcoma cells (7).
SIGNOR-265759
O15105
Q9H0M0
0
relocalization
up-regulates activity
0.731
We found that WWP1 inhibited transcriptional activities induced by TGF-beta. Similar to Smurfs, WWP1 associated with Smad7 and induced its nuclear export, and enhanced binding of Smad7 to TGF-beta type I receptor to cause ubiquitination and degradation of the receptor.
SIGNOR-126578
Q8TCS8
P78527
0
phosphorylation
up-regulates activity
0.2
We also demonstrated that DNAPK phosphorylates PNPase at Ser-776, which is critical for its ribonuclease activity.
SIGNOR-263182
Q9Y478
Q13131
0
phosphorylation
up-regulates
0.925
Mutation of serine 108 to alanine, an autophosphorylation site within the glycogen binding domain of the beta1 subunit, almost completely abolishes activation of ampk by a-769662 in cells and in vitro, while only partially reducing activation by amp
SIGNOR-157553
Q8TEW0
Q05513
0
phosphorylation
up-regulates
0.711
These results imply that serine 827 in the apkc binding site of par-3 is a target of apkc and that the regulated interaction between a protein kinase, apkc, and its substrate, par-3, plays an essential role in the establishment of cell polarity
SIGNOR-94523
P17480
P28482
0
phosphorylation
down-regulates
0.394
Erk1/2 was found to phosphorylate the architectural transcription factor ubf at amino acids 117 and 201 within hmg boxes 1 and 2, preventing their interaction with dna
SIGNOR-112809
P23771
Q99717
0
transcriptional regulation
up-regulates quantity
0.31
Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation
SIGNOR-268943
Q8N2W9
Q05513
0
phosphorylation
down-regulates quantity by destabilization
0.519
In this study, we discovered a new protein isoform encoded by KIAA0317, termed fibrosis-inducing E3 ligase 1 (FIEL1), which potently stimulates the TGFbeta signaling pathway through the site-specific ubiquitination of PIAS4.FIEL1 targets PIAS4 using a double locking mechanism that is facilitated by the kinases PKCzeta and GSK3beta. Specifically, PKCzeta phosphorylation of PIAS4 and GSK3beta phosphorylation of FIEL1 are both essential for the degradation of PIAS4.|These experiments suggested that PKCzeta is an authentic regulator of PIAS4 protein stability; Q21 and phosphorylated S18 of PIAS4 are both required for FIEL1 interaction.
SIGNOR-275513
Q9H2X6
P26367
1
phosphorylation
up-regulates activity
0.463
HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300. Mass spectrometric analysis identified three Pax6 phosphorylation sites as threonines 281, 304, and 373.
SIGNOR-251271
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
Q9UPX8
Q9Y2H0
0
relocalization
up-regulates activity
0.744
SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).
SIGNOR-264596
O14773
O76064
0
ubiquitination
up-regulates activity
0.302
Our data demonstrate that RNF8 directly ubiquitylates and stabilizes TPP1 at telomeres.|Taken together, these results suggest that RNF8 dependent K63 linked, but not K48 linked ubiquitin chain formation on TPP1 is required to promote TPP1 stability and function at telomeres.
SIGNOR-278574
P60709
O95631
0
post transcriptional regulation
up-regulates quantity
0.28
Netrin-1 induces β-actin translation driven by its 3’UTR.
SIGNOR-268161
P68400
Q92769
1
phosphorylation
up-regulates
0.619
Protein kinase ck2-mediated phosphorylation of hdac2 regulates co-repressor formation, deacetylase activity and acetylation of hdac2 by cigarette smoke and aldehydesstudies using unfractionated cell extracts with ck2 inhibitors suggest that protein kinase ck2 is the major source of hdac2 kinase. Finally, and perhaps most interesting, hdac2 phosphorylation promotes enzymatic activity, selectively regulates complex formation, but has no effect on transcriptional repression. Together, our data indicate that like many hdacs, hdac2 is regulated by post-translational modification, particularly phosphorylation.
SIGNOR-164795
P54646
Q92786
1
phosphorylation
down-regulates quantity by destabilization
0.2
Furthermore, the Ser79 phosphorylation of PROX1 by AMPK enhances the recruitment of CUL4-DDB1 ubiquitin ligase to promote PROX1 degradation.
SIGNOR-277608
P54829
P42262
1
dephosphorylation
down-regulates activity
0.412
One study showed that stimulation of the metabotrophic glutamate receptor mGluR5 leads to a STEP mediated tyrosine dephosphorylation of GluA2 and internalization of GluA1 and GluA2, although the tyrosine residue on GluA2 that is dephosphorylated by STEP remains unidentified.
SIGNOR-277040
P35813
O15169
1
dephosphorylation
down-regulates
0.435
Pp2c utilizes axin as a substrate both in vitro and in vivo and decreases its half-life. These results indicate that pp2c is a positive regulator of wnt signal transduction and mediates its effects through the dephosphorylation of axin.
SIGNOR-74231
Q96BR1
Q96PU5
1
phosphorylation
down-regulates activity
0.445
Moreover, S422DSGK1, SGK1, and SGK3 also phosphorylated Nedd4-2 and thereby inhibited Nedd4-2 binding to its target.
SIGNOR-280125
Q15139
O60602
1
phosphorylation
up-regulates
0.353
Pkd phosphorylated the tlr5-derived target peptide in vitro, and phosphorylation of the putative target serine 805 in hek 293t cell-derived tlr5 was identified by mass spectrometry. These results demonstrate that both pkd1 and pkd2 are required for inflammatory responses following tlr2, tlr4, or tlr5 activation, although pkd1 is more strongly involved
SIGNOR-154473
Q12933
P19438
0
null
up-regulates
0.832
We found that TNF-R1-mediated IKK activation requires both RIP and TRAF2 proteins. Although TRAF2 or RIP can be independently recruited to the TNF-R1 complex, neither one of them alone is capable of transducing the TNF signal that leads to IKK activation
SIGNOR-256251
Q9UBS5
Q9UQM7
0
phosphorylation
down-regulates
0.237
Nmda-dependent internalization of gabab receptors requires activation of ca2+/calmodulin-dependent protein kinase ii (camkii), which associates with gabab receptors in vivo and phosphorylates serine 867 (s867) in the intracellular c terminus of the gabab1 subunit.
SIGNOR-166846
P68400
P19447
1
phosphorylation
down-regulates activity
0.2
Phosphorylation of S751 by CKII inhibits 5′ incision.
SIGNOR-276013
Q8N4X5
P07949
0
phosphorylation
up-regulates activity
0.33
RET/PTC induced robust tyrosine phosphorylation of XB130, which promoted its subsequent association with the p85alpha subunit of phosphatidylinositol 3-kinase (PI 3-kinase). We identified tyrosine 54 of XB130 as the major target of RET/PTC-mediated phosphorylation and a critical binding site for the SH2 domains of p85alpha.
SIGNOR-263192
O60260
Q9NX47
0
ubiquitination
down-regulates quantity by destabilization
0.2
MITOL promotes cell survival by degrading Parkin during mitophagy.|Mechanistically, MITOL mediates ubiquitination of Parkin at lysine 220 residue, which promotes its proteasomal degradation, and thereby fine-tunes mitophagy by controlling the quantity of Parkin.
SIGNOR-278554
P52789
P12931
0
phosphorylation
up-regulates activity
0.362
Here we find that c-Src can interact with and phosphorylate hexokinases HK1 and HK2, the rate limiting enzymes in glycolysis.|Moreover, c-Src could efficiently stimulate the catalytic activities of HK1 and HK2, but failed to stimulate their corresponding mutants (XREF_FIG and XREF_SUPPLEMENTARY).
SIGNOR-278499
P04637
P28482
0
phosphorylation
up-regulates activity
0.778
In summary, our results suggest that phosphorylation of p53Thr55 by ERK2 is important for doxorubicin-induced p53 activation and cell death.
SIGNOR-279068
Q9Y4K3
P03186
0
deubiquitination
down-regulates activity
0.2
EBV-encoded BPLF1 interacts with and deubiquitinates TRAF6 to inhibit NF-κB signaling during lytic infection. Once lytic replication is induced, BPLF1 then deubiquitinates and inactivates TRAF6 to further block NF-κB signaling, promoting efficient viral genome replication.
SIGNOR-266739
P42768
P07948
0
phosphorylation
up-regulates activity
0.378
We demonstrated that WASP is phosphorylated on tyrosine 291 in macrophages, and the WASP phosphorylation is important for the phagocytic cup formation. In addition, we showed that WASP and WASP-interacting protein (WIP) form a complex at the phagocytic cup and that the WASP.WIP complex plays a critical role in the phagocytic cup formation. 
SIGNOR-273959
Q13224
P17612
0
phosphorylation
up-regulates activity
0.414
Here we identify serine residue 1166 (Ser1166) in the carboxy-terminal tail of the NMDAR subunit GluN2B to be a direct molecular and functional target of PKA phosphorylation critical to NMDAR-dependent Ca(2+) permeation and Ca(2+) signaling in spines.
SIGNOR-276616
O95817
Q05655
0
phosphorylation
up-regulates
0.251
Pkc_-mediated phosphorylation of bag3 at ser187 site induces epithelial-mesenchymal transition and enhances invasiveness in thyroid cancer fro cells. we showed that bag3 was implicated in epithelial-mesenchymal transition (emt) procedure, and phosphorylation state at ser187 site had a critical role in emt regulation by bag3.
SIGNOR-199316
P62136
P07737
1
dephosphorylation
up-regulates
0.247
Knockdown of the catalytic subunit of pp1 (pp1c_), but not pp2a (pp2ac_), increased ps137-pfn1 levels. Pp1c_ binds pfn1 in cultured cells, and this interaction was increased by a phosphomimetic mutation of pfn1 at ser-137 (s137d). Together, these data define pp1 as the principal phosphatase for ser-137 of pfn1
SIGNOR-196816
Q14469
P53805
1
transcriptional regulation
down-regulates quantity by repression
0.2
Increased Calcineurin/NFAT activity by Notch signaling involves downregulation of Calcipressin, an endogenous Calcineurin inhibitor, through a HES-1-dependent mechanism .... Chromatin immunoprecipitation (ChIP) analysis of keratinocytes overexpressing HES-1 showed that this protein can bind to the HES binding sites present in both distal and proximal promoters
SIGNOR-252026
Q9GZQ8
Q9Y4P1
0
cleavage
up-regulates
0.803
Human atg4 homologues cleave the carboxyl termini of the three human atg8 homologues, microtubule-associated protein light chain 3 (lc3), gabarap, and gate-16.
SIGNOR-125449
O60266
Q13555
0
phosphorylation
down-regulates activity
0.353
Phosphorylation and inhibition of type III adenylyl cyclase by calmodulin-dependent protein kinase II in vivo. | Site-directed mutagenesis of a CaM kinase II consensus site (Ser-1076 to Ala-1076) in III-AC greatly reduced Ca2+-stimulated phosphorylation and inhibition of III-AC in vivo.
SIGNOR-250691
P55085
P35030
0
cleavage
up-regulates activity
0.388
Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3.
SIGNOR-263604
Q96PU5
Q9NRA0
1
ubiquitination
down-regulates quantity by destabilization
0.2
In this study, we found that NEDD4L interacted with SphK2 to ubiquitinate SphK2 protein.|NEDD4L Mediates the Degradation of SphK2 Protein Through the Ubiquitin-Proteasomal Pathway.
SIGNOR-278660
P07355
Q75N03
0
ubiquitination
down-regulates quantity by destabilization
0.2
By immunoprecipitation, we present evidence that Hakai interacts with Hsp90 chaperone complex in several epithelial cells and demonstrate that is a novel Hsp90 client protein. Interestingly, by overexpressing and knocking-down experiments with Hakai, we identified Annexin A2 as a Hakai-regulated protein. Interestingly, geldanamycin-induced Hakai degradation is accompanied by an increased expression of E-cadherin and Annexin A2.
SIGNOR-271473
Q13936
P12931
0
phosphorylation
up-regulates activity
0.443
Cotransfection of human embryonic kidney (HEK)-293 cells with hCa(v)1.2b and c-Src resulted in tyrosine phosphorylation of the calcium channel, which was prevented by nitration of tyrosine residues by peroxynitrite. Whole cell calcium currents were reduced by 58 + 5% by the Src kinase inhibitor PP2 and 64 + 6% by peroxynitrite. 
SIGNOR-276081
O00213
O00141
0
phosphorylation
down-regulates activity
0.345
In the present study, we demonstrated that phosphorylation of FE65 Ser 610 by SGK1 attenuates the interaction between FE65 and APP (XREF_FIG).|In this regard, we demonstrated that phosphorylation of FE65 Ser 610 by SGK1 abolishes the effect of FE65 on APP processing and the amount of secreted Abeta is comparable to APP + Mock control (XREF_FIG).
SIGNOR-278220
P04637
P50750
0
phosphorylation
up-regulates
0.535
We recently demonstrated that through their physical interaction, cdk9 phosphorylates p53 on ser-392, leading to p53 stability and accumulation
SIGNOR-201935
Q04912
P00533
0
phosphorylation
up-regulates activity
0.334
This showed that EGFR activation transphosphorylated Ron.|Together, these data suggested that (1) Ron activation transphosphorylated EGFR and vice versa and (2) activated Ron biochemically interacted with EGFR.
SIGNOR-280000
P00519
O60234
1
phosphorylation
down-regulates activity
0.2
Acetylcholine stimulation also increased GMF-γ phosphorylation at Tyr-104. GMF-γ phosphorylation at this residue was mediated by c-Abl tyrosine kinase. The GMF-γ mutant Y104F (phenylalanine substitution at Tyr-104) had higher association with Arp2 in HASM cells upon contractile activation.Furthermore, expression of mutant Y104F GMF-γ attenuated actin polymerization and contraction in smooth muscle.
SIGNOR-273536
Q01726
Q8IUH4
0
palmitoylation
up-regulates activity
0.274
Collectively these results suggest that ZDHHC13 phosphorylation by ATR following UVB irradiation promotes its interaction with MC1R to stimulate MC1R palmitoylation.Activating MC1R palmitoylation rescues the defect of MC1R RHC variants
SIGNOR-273518
P06239
Q05655
1
phosphorylation
up-regulates activity
0.526
The tyrosine phosphorylation sites of PKC delta in the H(2)O(2)-treated cells were identified as Tyr-311, Tyr-332, and Tyr-512 by mass spectrometric analysis with the use of the precursor-scan method and by immunoblot analysis with the use of phosphorylation site-specific antibodies. Tyr-311 was the predominant modification site among them. In an in vitro study, phosphorylation at this site by Lck, a non-receptor-type tyrosine kinase, enhanced the basal enzymatic activity and elevated its maximal velocity in the presence of diacylglycerol. phosphorylation at Tyr-311 between the regulatory and catalytic domains is a critical step for generation of the active PKC delta in response to H(2)O(2).
SIGNOR-251386
Q16695
Q9Y4C1
0
demethylation
up-regulates activity
0.2
Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. 
SIGNOR-276846
P23467
P33151
1
dephosphorylation
up-regulates activity
0.581
Because we had shown previously that VE-PTP supports VE-cadherin function when exogenously expressed in transfected cells, we expected it to be expressed at endothelial cell contacts.|Indeed, tyrosine phosphorylation of VE-cadherin is reduced by VE-PTP in COS-7 and CHO cells.
SIGNOR-277131
Q13627
Q52LA3
1
phosphorylation
up-regulates activity
0.681
Here we report that DYRK1A can specifically phosphorylate LIN52 on serine residue 28, and that this phosphorylation is required for DREAM assembly.
SIGNOR-262846
P48729
Q9UGI0
1
phosphorylation
up-regulates activity
0.2
Interestingly, ZRANB1 is phosphorylated at Thr35, and Ser209 residues by CSNK1A1, and this phosphorylation activates its deubiquitinating activity.
SIGNOR-273621
O00254
Q15835
0
phosphorylation
down-regulates activity
0.2
For example, RhoK phosphorylates and inhibits TIAM1, STEF, and PAR3; disrupts the polarity complex; and prevents Rac activation ( xref ).
SIGNOR-279993
Q9NVW2
Q86U70
1
polyubiquitination
down-regulates quantity by destabilization
0.566
Here we identify RLIM as a ubiquitin protein ligase that is able to target CLIM cofactors for degradation through the 26S proteasome pathway. 
SIGNOR-272617
Q9Y6K9
P06241
0
phosphorylation
down-regulates activity
0.357
Either IKKγ/NEMO WT or the Y374F mutant was coexpressed with each member of the Src family protein tyrosine kinases (SF-PTKs) in HEK 293T cells. Our study thus demonstrates that the Y374 or S377 residue located at the C-terminal proline-rich domain of human IKKγ/NEMO undergoes phosphorylation upon TNF-α treatment or KvFLIP expression, respectively, resulting in the suppression of IKKγ/NEMO activity to induce NF-κB activation. 
SIGNOR-276371
O60936
Q05086
0
ubiquitination
down-regulates quantity by destabilization
0.2
Incubation of transfected HEK293T cells with the proteasome inhibitor, MG132 blocked Ube3A mediated degradation of Arc suggesting that Ube3A degrades Arc via the ubiquitin proteasome system .|The ubiquitination of Arc by Ube3A was confirmed by mass spectrometry which revealed that Ube3A catalyzed the polyubiquitination of Arc on Lysine 268 and 269 ( xref ).
SIGNOR-278522
P54198
P31749
0
phosphorylation
up-regulates activity
0.2
Consistently, HIRA phosphorylation was effectively decreased by Akt1 knockdown and was completely eliminated by the depletion of both Akt1 and Akt2, suggesting that HIRA is phosphorylated primarily by Akt1 and that Akt2 seemed to contribute to HIRA phosphorylation as a supplementary kinase in myoblasts (XREF_FIG).|In this study, HIRA was more efficiently targeted by Akt1 in myoblasts.
SIGNOR-279584
O43521
Q16539
0
phosphorylation
down-regulates quantity by destabilization
0.32
Ser69 can also be phosphorylated by JNK and p38MAPK at least in vitro. Phosphorylation of BimEL on Ser69 promotes its ubiquitination.
SIGNOR-260442
P21796
O00141
0
phosphorylation
down-regulates quantity
0.2
As hypothesized based upon our observation that activated SGK-1 reduces VDAC-1 protein levels, sgk-1 overexpression normalizes the shortened lifespan of vdac-1 transgenics .|Taken together, these data indicate that Ser104 phosphorylation of VDAC1 by SGK1 increases its ubiquitination and subsequent cellular clearance.
SIGNOR-278988
Q99523
Q13153
0
phosphorylation
down-regulates activity
0.2
PAKs specifically phosphorylate Ser15 of the sortilin-cd and alter its trafficking. It can be concluded that PAK1-3 may indeed instigate the phosphorylation of sortilin and that they target a single serine residue (Ser15) located in the kinase domain-binding site of the sortilin-cd. Full-length sortilins with the serine at position 793 (residue 15 in the cytoplasmic domain) (for the sequence, see Fig. 2). Phosphorylation (Ser15) downregulates the sortilin–AP-1 interaction.
SIGNOR-273718
P05067
P11802
0
phosphorylation
down-regulates quantity by destabilization
0.258
These include a significant increase in APP phosphorylation at Thr 668 by cdk2, cdk4, and cdk5, which increases its beta-amyloid production and APP proteolysis by the activated caspases during cell cycle ( xref ; xref ; xref ; xref ).
SIGNOR-280214
Q13164
P15056
0
phosphorylation
up-regulates quantity
0.292
Our data indicate that oncogenic BRAF increases ERK5 protein level, phosphorylation at several residues and kinase activity.|Overexpression of oncogenic BRAF induced ERK5 phosphorylation at Thr218 and Tyr220, although to a lower level than that induced by MEK5DD.
SIGNOR-278353
P06493
P51003
1
phosphorylation
up-regulates activity
0.258
Once an oocyte resumes meiosis, activated CDK1 and ERK1/2 cooperatively mediate the phosphorylation of three serine residues of PAPalpha, 537, 545 and 558, thereby leading to increased activity.
SIGNOR-268338
Q9NQU5
P04049
1
phosphorylation
up-regulates activity
0.2
PAK5 phosphorylates Raf-1 on serine 338 and stimulates Raf-1 activity.
SIGNOR-278971
P06241
P05067
1
phosphorylation
up-regulates quantity
0.451
Fyn induced phosphorylation of APP at Tyr-757 of the (757)YENPTY(762) motif and increased cell surface expression of APP.
SIGNOR-278378
Q13464
P48436
1
phosphorylation
up-regulates
0.305
Rho kinase-dependent activation of sox9 in chondrocytes. In vitro, rock directly phosphorylated sox9 at ser(181), and the overexpression of rock or the activation of the rhoa pathway in sw1353 chondrosarcoma cells increased sox9(ser181) phosphorylation
SIGNOR-162643
P06493
P67870
1
phosphorylation
up-regulates
0.459
In cells, the casein kinase ii beta-subunit is phosphorylated at an autophosphorylation site and at a site (ser-209) that is maximally phosphorylated in mitotic cells. These studies provide strong biochemical evidence that p34cdc2 is the enzyme that phosphorylates ser-209 on the beta-subunit of ckii in mitotic cells.
SIGNOR-29462
P42768
Q06187
0
phosphorylation
up-regulates activity
0.743
These results demonstrate that WASP, under this experimental condition, can be tyrosine-phosphorylated by the kinase activity of Btk and that the direct interaction between WASP and the SH3 domain of Btk is required for this phosphorylation to occur.
SIGNOR-273958
Q9BT67
Q9H0M0
0
ubiquitination
down-regulates quantity
0.381
Accordingly, the ubiquitination assays were performed and the results revealed that knockdown of WWP1 reduced the ubiquitination of NDFIP1 in HuCCT1 and vice versa in HCCC-9810 and RBE (Fig. 7E).|In addition, we found that WWP1 could reduce the protein level of NDFIP1 via ubiquitination.
SIGNOR-278796
Q13315
Q9BQ15
1
phosphorylation
up-regulates activity
0.501
Ataxia telangiectasia mutated (ATM) kinase phosphorylates hSSB1 in response to DNA double-strand breaks (DSBs). This phosphorylation event is required for DNA damage-induced stabilization of hSSB1.
SIGNOR-262639
P17252
P28698
0
transcriptional regulation
up-regulates quantity by expression
0.384
The luciferase reporter assay results revealed that the presence of both MZF-1 and Elk-1 significantly contributed to the upregulation of PKCα gene transcription activity.
SIGNOR-256337
Q8NG68
Q6PEY2
1
tyrosination
down-regulates
0.46
Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization
SIGNOR-176924
Q5VT25
P53667
1
phosphorylation
up-regulates activity
0.404
Activation of LIM kinases by myotonic dystrophy kinase-related Cdc42-binding kinase alpha. \ In vitro, MRCKalpha phosphorylated the protein kinase domain of LIM kinases, and the site in LIMK2 phosphorylated by MRCKalpha proved to be threonine 505 within the activation segment.
SIGNOR-250721
Q13542
P42345
0
phosphorylation
down-regulates
0.661
Here, we show that cancer cells acquire resistance to astori by downregulating eukaryotic translation initiation factor (eif4e)-binding proteins (4e-bps-eif4ebp1, eif4ebp2).
SIGNOR-122014
Q92519
Q9HCE7
0
ubiquitination
down-regulates quantity by destabilization
0.41
 In this study, we found that TRIB2 was up-regulated and exhibited high stability in liver cancer cells compared with other cells. We performed a structure-function analysis of TRIB2 and identified a domain (amino acids 1-5) at the N terminus that interacted with the E3 ubiquitin ligase Smurf1 and was critical for protein stability. Deletion of this domain extended TRIB2 half-life time accompanied with a more significant malignant property compared with wild type TRIB2.
SIGNOR-275432
O75581
Q9H0K1
0
phosphorylation
up-regulates activity
0.2
Mechanistically, SIK2, phosphorylated by CK1α, directly phosphorylated LRP6 in a SIK2 kinase activity-dependent manner, leading to Wnt/β-catenin signaling pathway activation.
SIGNOR-275399
P07384
P10636
1
cleavage
down-regulates activity
0.333
Besides tau phosphorylation, calpain activation might play a role in tau-mediated neurodegeneration by inducing tau cleavage. In vitro studies have shown that both fetal and adult tau isoforms are rapidly proteolyzed by calpains
SIGNOR-251584
O14965
O43379
1
phosphorylation
up-regulates activity
0.352
AURKA activity promotes WDR62 spindle localization|We next purified recombinant full-length WDR62 (GST–WDR62-FL) for in vitro kinase assays with active AURKA and demonstrated that WDR62 was a direct phosphorylation target of AURKA|In addition, our quantitative phosphoproteomic analysis of in-vitro-phosphorylated WDR62 identified S32 and S33 as significantly phosphorylated in the presence of active AURKA|Alanine replacement of the five putative phosphorylation sites (S32/S33/S49/T50/S52-AAAAA) of WDR62 attenuated interphase microtubule association induced by AURKA coexpression
SIGNOR-271713
P48729
O15534
1
phosphorylation
down-regulates quantity by destabilization
0.318
CKI\u03b1-Dependent Phosphorylation and Degradation of PER1.
SIGNOR-279700
P47712
P27361
0
phosphorylation
up-regulates
0.658
Activated map kinase phosphorylates cpla2 at ser-505, causing increased enzymatic activity of cpla2, which is only realized upon translocation of cpla2 to the membrane.
SIGNOR-38434
Q05655
Q99808
1
phosphorylation
up-regulates activity
0.2
Phosphorylation of hENT1 by PKC has effects on both the function and subcellular trafficking of hENT1
SIGNOR-260888
P19634
P51812
0
phosphorylation
up-regulates activity
0.414
In pressured arteries, RSK2 dependent activation of NHE-1 was associated with increased intracellular Ca 2+ transients, which would be expected to increase MLCK activity, thereby contributing to basal tone and myogenic responses.|Together, these data indicate that Ser 703 in NHE-1 is phosphorylated by RSK2, that RSK2 is associated with NHE-1, and that the time course of NHE-1 phosphorylation in response to intraluminal pressure is fast enough for this phosphorylation event to contribute to myogenic vasoconstriction.
SIGNOR-280119
P23771
P42226
0
null
up-regulates
0.662
GATA-3 plays a central role in regulating Th1 and Th2 cell differentiation. Upon interleukin (IL)-4 binding to its receptor, GATA-3 is induced through the action of Stat6
SIGNOR-254299
Q15306
O15054
0
transcriptional regulation
up-regulates quantity by expression
0.422
JMJD3 seems to function by controlling expression of the transcription factor IRF4, which in turn is required for M2 polarization of macrophages in vitro and in vivo. Although this pathway is strongly supported by genetic.
SIGNOR-249540
P32245
P25098
0
phosphorylation
down-regulates activity
0.2
Mutagenesis studies revealed that Thr312 and Ser329/330 in the C-terminal tail are potential sites for PKA and GRK phosphorylation and may play an essential role in the recruitment of beta-arrestin to the activated receptor.
SIGNOR-247770
P27708
P27361
0
phosphorylation
up-regulates
0.2
Cad is a multifunctional protein that initiates and regulates mammalian de novo pyrimidine biosynthesis. The activation of the pathway required for cell proliferation is a consequence of the phosphorylation of cad thr-456 by mitogen-activated protein (map) kinase.Activated map kinase (erk1/2), the enzyme responsible for the phosphorylation of thr-456, was also present in larger amounts in the nucleus than the cytosol
SIGNOR-137179
P98170
P31749
0
phosphorylation
up-regulates quantity by stabilization
0.618
Akt, including akt1 and akt2, interacts with and phosphorylates x-linked inhibitor of apoptosis protein (xiap) at residue serine-87 in vitro and in vivo. Phosphorylation of xiap by akt protects xiap from ubiquitination and degradation in response to cisplatin.
SIGNOR-119488
Q00613
P68400
0
phosphorylation
up-regulates activity
0.37
Transcriptional activity and DNA binding of heat shock factor-1 involve phosphorylation on threonine 142 by CK2.
SIGNOR-250898
P32121
Q14940
1
relocalization
down-regulates activity
0.397
Internalization of the Na(+)/H(+) exchanger NHE5 into recycling endosomes is enhanced by the endocytic adaptor proteins beta-arrestin1 and -2, best known for their preferential recognition of ligand-activated G protein-coupled receptors (GPCRs)
SIGNOR-275506