IdA
string | IdB
string | labels
int64 | mechanism
string | effect
string | score
float64 | sentence
string | signor_id
string |
|---|---|---|---|---|---|---|---|
P06748
|
O15111
| 0
|
phosphorylation
|
up-regulates activity
| 0.2
|
S125A and a delta form lacking the aa 119-195 region completely abolished NPM phosphorylation by IKKalpha (XREF_FIG), suggesting that IKKalpha phosphorylates S125 of NPM.|We found that TNFalpha treatment induced IKKalpha phosphorylation and increased NPM hexamers, which were correlated with increased NPM phosphorylation (XREF_FIG).
|
SIGNOR-279405
|
P43405
|
Q8N884
| 1
|
phosphorylation
|
up-regulates activity
| 0.2
|
Mechanistically, viral infection or foreign DNA transfection triggers recruitment of the spleen tyrosine kinase (SYK) and cGAS to the endosomal vacuolar H+ pump (V-ATPase), where SYK is activated and then phosphorylates human cGASY214/215 (mouse cGasY200/201) to prime its activation.
|
SIGNOR-277844
|
P48730
|
Q00987
| 1
|
phosphorylation
|
down-regulates
| 0.345
|
Phosphorylation by casein kinase i promotes the turnover of the mdm2 oncoprotein via the scf(beta-trcp) ubiquitin ligase.
|
SIGNOR-167497
|
P62820
|
P06493
| 0
|
phosphorylation
|
down-regulates activity
| 0.526
|
We now present biochemical evidence for a mitosis-specific p34cdc2 phosphorylation of RablAp and Rab4p.We also show that the distribution of RablAp and Rab4p between cytosolic and membrane-bound forms is different in interphase and mitotic cells.
|
SIGNOR-261284
|
P67775
|
P37840
| 1
|
dephosphorylation
|
down-regulates activity
| 0.332
|
α-Synuclein (α-Syn) is a key protein that accumulates as hyperphosphorylated aggregates in pathologic hallmark features of Parkinson's disease (PD) and other neurodegenerative disorders. Phosphorylation of this protein at serine 129 is believed to promote its aggregation and neurotoxicity, suggesting that this post-translational modification could be a therapeutic target. Here, we demonstrate that phosphoprotein phosphatase 2A (PP2A) dephosphorylates α-Syn at serine 129
|
SIGNOR-248635
|
O00410
|
Q8TD84
| 1
|
relocalization
|
up-regulates activity
| 0.2
|
DSCAM and DSCAML1 specifically interacted with the importin beta IPO5, whereas deletion of the identified NLSs abolished this specific interaction and suppressed nuclear translocation of the DSCAM/L1 ICDs in cell lines and cultured neurons. This suggests a direct role of IPO5 in the nuclear import of the DSCAM/L1 ICDs.
|
SIGNOR-264274
|
Q13451
|
Q9NZQ7
| 1
|
catalytic activity
|
up-regulates quantity by expression
| 0.2
|
FKBP51s upregulated PD-L1 expression on the plasma membrane by catalysing the protein folding required for subsequent glycosylation. Inhibition of FKBP51s isomerase activity by SAFit decreased PD-L1 levels
|
SIGNOR-274973
|
P16220
|
Q9Y4H2
| 1
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.342
|
Taken together, these results indicate that the IRS2 gene is a direct target for CREB action in vivo
|
SIGNOR-278145
|
P43405
|
Q92835
| 0
|
dephosphorylation
|
down-regulates activity
| 0.418
|
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-268456
|
Q13950
|
Q9UNE7
| 0
|
ubiquitination
|
down-regulates quantity by destabilization
| 0.407
|
Here, we show that CHIP promotes Runx2 ubiquitination and degradation and thereby negatively regulates osteoblast differentiation.
|
SIGNOR-278600
|
Q00535
|
Q9Y490
| 1
|
phosphorylation
|
up-regulates
| 0.458
|
Cdk5 phosphorylated talin head at ser 425, inhibiting its binding to smurf1, thus preventing talin head ubiquitylation and degradation.
|
SIGNOR-185210
|
P19634
|
O00141
| 0
|
phosphorylation
|
up-regulates activity
| 0.304
|
Phosphorylation of NHE1 Ser 703 by SGK1 is essential for the binding of 14-3-3 protein to NHE1 , ] which, in turn, is critical in the activation of this Na + / H + exchanger , ].|These data suggest that endothelial SGK1 activates NHE1 in response to MG treatment.
|
SIGNOR-280123
|
Q969S3
|
Q99683
| 0
|
phosphorylation
|
up-regulates
| 0.487
|
Ask1 directly phosphorylated zpr9 at ser(314) and thr(318), suggesting that zpr9 can act as an ask1 substrate. Ask1-mediated phosphorylation of zpr9 at ser(314) and thr(318) was also responsible for zpr9-induced apoptosis.
|
SIGNOR-175113
|
Q9UJQ4
|
Q9BXF3
| 1
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.2
|
SALL4 activates Cecr2 by directly binging to its promotor region and CECR2 in turn promotes reprogramming through forming a SMARCA1-contained chromatin remodeling complex with its DTT domain.
|
SIGNOR-263893
|
O15297
|
Q9H0Z9
| 1
|
dephosphorylation
|
up-regulates activity
| 0.363
|
Interestingly, we showed that PPM1D directly interacts with and dephosphorylates RBM38 at serine 195.
|
SIGNOR-277020
|
O15169
|
P62136
| 0
|
dephosphorylation
|
down-regulates activity
| 0.333
|
The data suggest that PP1 controls Wnt signaling through interaction with, and regulated dephosphorylation of, axin| Axin phosphorylation markedly enhances the binding of glycogen synthase kinase 3, leading to a more active beta-catenin destruction complex. Wnt-regulated changes in axin phosphorylation, mediated by PP1, may therefore determine beta-catenin transcriptional activity| Four sites, S80, S82, S222, and S473, were identified to be PP1 regulated
|
SIGNOR-248551
|
P53350
|
Q12888
| 1
|
phosphorylation
|
down-regulates activity
| 0.596
|
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 |Addition of the inhibitors for PLK1 and the p38 MAPK leads to a complete loss of pT1609/pS1618 signal within 3 hr in mitotic cells
|
SIGNOR-264413
|
P01137
|
P14780
| 0
|
cleavage
|
up-regulates
| 0.592
|
We also demonstrate that mmp-9, as well as its relative, mmp-2, cleave latent transforming growth factor-_ (tgf-_), which constitutes a novel mechanism of tgf-_ activation.
|
SIGNOR-74461
|
P68400
|
Q9NQB0
| 1
|
phosphorylation
|
up-regulates activity
| 0.358
|
We show here that Tcf-4 can be phosphorylated in vitro by protein kinase CK2 stoichiometrically in amino acids Ser-58-Ser-59-Ser-60. Phosphorylation of these residues does not modify the interaction of Tcf-4 with beta-catenin but reduces its association to plakoglobin. | Experiments performed using a Tcf-4 mutant with decreased interaction to plakoglobin demonstrated that binding to this protein negatively affected the transcriptional activity of Tcf-4.
|
SIGNOR-250963
|
P52565
|
Q13153
| 0
|
phosphorylation
|
down-regulates
| 0.611
|
Pak1 binds and phosphorylates rhogdi both in vitro and in vivo at ser101 and ser174. This resulted in dissociation of rac1-rhogdi, but not rhoa-rhogdi, complexes, as determined by in vitro assays of complexation and in vivo by coimmunoprecipitation analysis. We observed that cdc42-induced rac1 activation is inhibited by expression of pak1 autoinhibitory domain. The dissociation of rac1 from rhogdi and its subsequent activation stimulated by pdgf or egf is also attenuated by pak1 autoinhibitory domain, and this is dependent on the ability of rhogdi to be phosphorylated at ser101/174.
|
SIGNOR-126654
|
O00533
|
Q12955
| 1
|
relocalization
|
up-regulates quantity
| 0.412
|
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 ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.
|
SIGNOR-266723
|
Q05397
|
P49841
| 1
|
phosphorylation
|
up-regulates activity
| 0.365
|
Inhibition of FAK by its small molecule inhibitor attenuated IL-33-induced tyrosine 216 phosphorylation of GSK3beta in a both time- and dose dependent manner (XREF_FIG).|The current study indicates that FAK activated GSK3beta modulates ST2L internalization and signaling.
|
SIGNOR-278986
|
Q86Y13
|
P04908
| 1
|
monoubiquitination
|
up-regulates activity
| 0.2
|
2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.
|
SIGNOR-271747
|
P26447
|
O94916
| 0
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.478
|
As expected, the depletion of NFAT5 decreased the S100A4 and LCN2 mRNA levels (Figure 3a). In addition, chromatin immunoprecipitation (ChIP) assay using NFAT5 antibody indicated that NFAT5 was bound to the S100A4 and LCN2 promoters (Figure 3b, Supplementary Figure S3), as expected (Chen et al., 2009).
|
SIGNOR-274115
|
P01024
|
P08311
| 0
|
cleavage
|
up-regulates activity
| 0.599
|
Plasma membrane elastase and cathepsin G from U937 cells cleave C3 into C3a- and C3b-like fragments; further incubation leads to C3c- and C3dg-like fragments, as judged from SDS-PAGE analysis of the digests. Sequencing of the C3b-like fragment purified by reverse phase chromatography indicates that initial cleavage of C3 by purified cathepsin G occurs at two positions in the amino-terminal part of the alpha-chain, at a Arg-Ser bond located between residues 748 and 749 and at a Leu-Asp bond between residues 751 and 752.
|
SIGNOR-256348
|
Q92831
|
Q6NXT2
| 1
|
acetylation
|
down-regulates activity
| 0.2
|
The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.
|
SIGNOR-269617
|
P18031
|
Q13882
| 1
|
dephosphorylation
|
down-regulates activity
| 0.575
|
Using a variety of PTEN mutant constructs, we show that protein phosphatase activity of PTEN targets PTK6, with efficiency similar to PTP1B, a phosphatase that directly dephosphorylates PTK6 Y342.
|
SIGNOR-277082
|
O15111
|
Q92905
| 1
|
phosphorylation
|
down-regulates activity
| 0.325
|
Overexpression of IKKalpha or IKKbeta leads to enhanced phosphorylation of CSN5, the catalytic subunit for CSN deneddylase activity. Mutational analyses have revealed that phosphorylation at serine 201 and threonine 205 of CSN5 impairs CSN-mediated deneddylation activity in vitro.
|
SIGNOR-275507
|
O43395
|
Q9UMS4
| 0
|
polyubiquitination
|
up-regulates activity
| 0.754
|
Here, we report that the spliceosomal Prp19 complex modifies Prp3, a component of the U4 snRNP, with nonproteolytic K63-linked ubiquitin chains. The K63-linked chains increase the affinity of Prp3 for the U5 snRNP component Prp8, thereby allowing for the stabilization of the U4/U6.U5 snRNP.
|
SIGNOR-271966
|
Q04759
|
Q9UEW8
| 1
|
phosphorylation
|
up-regulates activity
| 0.487
|
Recombinant SPAK was phosphorylated on Ser-311 in its kinase domain by PKCtheta, but not by PKCalpha. This synergistic activity, as well as the receptor-induced SPAK activation, required the PKCtheta-interacting region of SPAK, and Ser-311 mutation greatly reduced these activities of SPAK.
|
SIGNOR-276007
|
P67775
|
O14757
| 1
|
dephosphorylation
|
down-regulates activity
| 0.496
|
Phosphorylation of Chk1 by ATR is antagonized by a Chk1-regulated protein phosphatase 2A circuit|In response to genotoxic stress, Chk1 is phosphorylated on serines 317 (S317) and 345 (S345) by the ataxia-telangiectasia-related (ATR) protein kinase. Phosphorylation of Chk1 on these C-terminal serine residues is used as an indicator of Chk1 activation in vivo.
|
SIGNOR-248615
|
P04792
|
Q05655
| 0
|
phosphorylation
|
down-regulates activity
| 0.515
|
Radioactive kinase assays confirmed that PKC\u03b4 phosphorylated Hsp27 at Ser78 and Ser82 ( Fig. 3 B).
|
SIGNOR-278425
|
Q00987
|
P37231
| 1
|
ubiquitination
|
down-regulates quantity by destabilization
| 0.389
|
Here, we found that nuclear EGFR induced phosphorylation of PPARγ at Tyr-74 leading to PPARγ ubiquitination and degradation by mouse double minute 2 (MDM2) ubiquitin ligase.
|
SIGNOR-277191
|
Q9UI09
|
P06493
| 0
|
phosphorylation
|
up-regulates activity
| 0.2
|
Here, we show that a fraction of cyclin B1/Cdk1 proteins localizes to the matrix of mitochondria and phosphorylates a cluster of mitochondrial proteins, including the complex I (CI) subunits in the respiratory chain. Cyclin B1/Cdk1-mediated CI phosphorylation enhances CI activity, whereas deficiency of such phosphorylation in each of the relevant CI subunits results in impairment of CI function.|These results were confirmed by generating phosphorylation defective forms of the five CI subunits through substitutions of S/T residues with Alanine (A) on either Cdk1 optimal or minimal consensus motifs (T383 on NDUFV1, S105 on NDUFV3, S364 on NDUFS2, S55/S29/T5 on NDUFB6, and T142/T120 on NDUFA12). The mutation of Cdk1 consensus motifs severely diminished their phosphorylation
|
SIGNOR-275587
|
P32121
|
P32248
| 0
|
relocalization
|
up-regulates activity
| 0.377
|
B-Arrestin-2 is recruited to CCR7 following stimulation with CCL19, but not CCL21.
|
SIGNOR-278124
|
P05067
|
Q86TM6
| 0
|
ubiquitination
|
down-regulates quantity by destabilization
| 0.339
|
Thus, HRD1 ubiquitinates and degrades denaturated APP as well as unfolded proteins, suggesting that HRD1 affects APP-A\u03b2 dynamics in the brains of AD patients.
|
SIGNOR-278616
|
P43405
|
Q9NRF2
| 0
|
dephosphorylation
|
down-regulates activity
| 0.2
|
SHP-1 is recruited by the phosphorylated ITIM-bearing receptors such as CD22 and it dephosphorylates proximal BCR signaling molecules such as CD79, SYK, BLNK.
|
SIGNOR-268445
|
P19237
|
Q969Q1
| 0
|
polyubiquitination
|
down-regulates quantity by destabilization
| 0.36
|
We used MuRF1 as the E3 as it functions with all these E2s to ubiquitinate one of its typical substrates, troponin I Although UbcH1 and UbcH13/Uev1a support ubiquitination of troponin I by MuRF1, these E2s do not support ubiquitination of S5a, unlike Class I E2s.
|
SIGNOR-272736
|
Q6GQQ9
|
Q13546
| 1
|
deubiquitination
|
down-regulates activity
| 0.538
|
NF-kappaB Suppression by the Deubiquitinating Enzyme Cezanne|Our study provides several lines of evidence to suggest that Cezanne suppresses TNFR signaling to NF-κB by targeting RIP1 for deubiquitination.
|
SIGNOR-268411
|
Q9UNQ0
|
P11309
| 0
|
phosphorylation
|
up-regulates activity
| 0.36
|
Pim-1 kinase phosphorylates BCRP/ABCG2 and thereby promotes its multimerization and drug-resistant activity in human prostate cancer cells|This is further corroborated by our finding that the plasma membrane localization and drug-resistant activity of BCRP were compromised by T362A mutation.
|
SIGNOR-264420
|
P35711
|
Q8IYA7
| 0
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.295
|
MKX is a meniscus-enriched transcription factor. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2).
|
SIGNOR-267214
|
P11233
|
O14965
| 0
|
phosphorylation
|
up-regulates activity
| 0.45
|
Specifically, the mitotic kinase Aurora A phosphorylates Ser 194 of RALA, relocalizing it to the mitochondria, where it concentrates RALBP1 and DRP1.|These data suggest that Aurora A promotes mitochondrial fission at mitosis through RalA and RalBP1.
|
SIGNOR-278351
|
Q96GD4
|
P56524
| 1
|
phosphorylation
|
down-regulates
| 0.264
|
We define the precise site of aurb-mediated phosphorylation as a conserved serine within the nuclear localization signals of hdac4, hdac5, and hdac9 at ser265, ser278, and ser242, respectivelyduring mitosis, aurb-mediated phosphorylation may localize class iia hdacs to a phosphorylation gradient at the spindle midzone, permitting temporal and spatial regulatory mechanisms altering hdac protein interactions
|
SIGNOR-198646
|
O15294
|
P17858
| 1
|
glycosylation
|
down-regulates activity
| 0.277
|
O-GlcNAcylation was induced at serine 529 of phosphofructokinase 1 (PFK1) in response to hypoxia. Glycosylation inhibited PFK1 activity and redirected glucose flux through the pentose phosphate pathway| O-GlcNAc transferase (OGT) catalyzes the transfer of N-acetylglucosamine from uridine diphospho-N-acetylglucosamine (UDP-GlcNAc) to serine or threonine residues
|
SIGNOR-267585
|
Q13043
|
P04406
| 1
|
phosphorylation
|
up-regulates activity
| 0.279
|
Interestingly, GAPDH is phosphorylated by Mst1 to a comparable extent as its known substrate MBP, suggesting that GAPDH is a good substrate of Mst1 at least in vitro.|Moreover, interaction of Mst1 with GAPDH caused a robust phosphorylation of GAPDH and markedly increased the Mst1 activity in cells.
|
SIGNOR-279295
|
Q99250
|
P49841
| 0
|
phosphorylation
|
down-regulates activity
| 0.2
|
Glycogen synthase kinase 3β (GSK3beta) phosphorylates the Nav1.2C-terminal tail at T1966, suppressing Na+ currents and channel trafficking to the plasma membrane
|
SIGNOR-275748
|
Q92519
|
P23443
| 0
|
phosphorylation
|
down-regulates quantity by destabilization
| 0.356
|
Furthermore, Smurf1-mediated ubiquitination required phosphorylation of TRIB2 by p70 S6 kinase (p70S6K) via another domain (amino acids 69-85) that is also essential for correct TRIB2 subcellular localization. Mutation of Ser-83 diminished p70S6K-induced phosphorylation of TRIB2.
|
SIGNOR-275433
|
P49841
|
P27361
| 0
|
phosphorylation
|
down-regulates activity
| 0.294
|
We demonstrate that insulin-mediated activation of ERK1/2 results in phosphorylation of GSK3β at S9 independently of Akt/mTORC1 activity in Tsc2 null mouse embryonic fibroblasts. In addition, we show that inhibition of ERK1/2 rescues GSK3β activity and restores protein synthesis in Tsc2 −/− MEFs to normal levels
|
SIGNOR-262523
|
P54753
|
P46527
| 1
|
phosphorylation
|
down-regulates activity
| 0.2
|
In accord with this concept are the findings of Vlach et al. , who have studied point mutants of p27 deficient in their interactions with EK2, and have found that T187 phosphorylation of p27 by EK2 requires an interaction of p27 with the cyclin E subunit, while inhibition of the kinase activity requires an additional interaction with the CDK2 subunit.|The question considered here is the theoretical question whether deactivation of p27 by EK2 can produce binary EK2 release, and if so what biochemical kinetic features are required for this behavior.
|
SIGNOR-279406
|
Q05655
|
P04637
| 1
|
phosphorylation
|
up-regulates
| 0.677
|
Here, we show that the pro-apoptotic kinase, protein kinase c delta (pkcdelta), is involved in phosphorylation of p53 on ser(46). pkcdelta potentiates p53-dependent apoptosis by ser(46) phosphorylation in response to genotoxic stress.
|
SIGNOR-143382
|
P49715
|
Q13547
| 0
|
transcriptional regulation
|
down-regulates
| 0.436
|
These data suggest that c/ebp beta activates a single unified pathway of adipogenesis involving its stimulation of ppargamma expression, which then activates c/ebp alpha expression by dislodging hdac1 from the promoter for degradation in the proteasome
|
SIGNOR-210013
|
P62841
|
Q5S007
| 0
|
phosphorylation
|
up-regulates activity
| 0.485
|
Taken together, these results suggest that phosphorylation of s15 on T136 by LRRK2 mediates enhanced cap-dependent and cap-independent reporter translation and that a stimulatory effect of LRRK2 on mRNA translation contributes to LRRK2 toxicity.
|
SIGNOR-279058
|
Q96M02
|
P04637
| 1
|
polyubiquitination
|
up-regulates quantity by stabilization
| 0.459
|
The E3 activity of FATS is required for promoting p53 stability and activation in response to DNA damage.FATS is an E2-independent ubiquitin ligase that stabilizes p53 and promotes its activation in response to DNA damage. Here, we show that FATS acts as a p53 activator by inhibiting Mdm2 binding to p53 and stimulating non-proteolytic polyubiquitination of p53.
|
SIGNOR-272142
|
Q9BR01
|
P27361
| 0
|
phosphorylation
|
down-regulates
| 0.2
|
The phosphorylation of sult4a1 allows interaction with pin1, which then promotes degradation of the sulfotransferase.
|
SIGNOR-168248
|
Q9H2X6
|
Q92793
| 1
|
phosphorylation
|
up-regulates activity
| 0.424
|
Moreover, we show that HIPK2 strongly potentiates the transcriptional activity of CREB-binding protein.|We show that HIPK2 interacts with and phosphorylates several regions of CBP.
|
SIGNOR-279191
|
Q76I76
|
P23528
| 1
|
dephosphorylation
|
up-regulates activity
| 0.732
|
Differential activities, subcellular distribution and tissue expression patterns of three members of Slingshot family phosphatases that dephosphorylate cofilin.|Cofilin, a key regulator of actin filament dynamics, is inactivated by phosphorylation at Ser-3 by LIM-kinases and is reactivated by dephosphorylation by a family of protein phosphatases, termed Slingshot (SSH).
|
SIGNOR-248733
|
P40763
|
O14543
| 1
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.709
|
We also found that the wild type SOCS-3 promoter construct has significantly greater activity in non-small-cell lung cancer cell lines than in normal cells in accordance with STAT3 disregulation in these cells
|
SIGNOR-253583
|
P30307
|
P14635
| 1
|
dephosphorylation
|
up-regulates activity
| 0.832
|
Cdc25C is an activator of Cdc2 kinase and dephosphorylates and activates the CyclinB-Cdc2 complex shortly before the entry into the mitosis.
|
SIGNOR-277099
|
Q00987
|
Q02878
| 1
|
ubiquitination
|
down-regulates quantity by destabilization
| 0.432
|
Furthermore, we also demonstrated that RPL6 is a substrate for HDM2-mediated ubiquitination and proteasomal degradation.|The interaction of RPL6 and HDM2 drives HDM2 mediated RPL6 polyubiquitination and proteasomal degradation.
|
SIGNOR-278630
|
Q9UPP1
|
P28482
| 0
|
phosphorylation
|
down-regulates activity
| 0.2
|
Upon IFNgamma treatment, PHF8 is phosphorylated by ERK2 and evicted from the promoters, which correlates with an increase in H4K20me1 and H3K4me3 levels.
|
SIGNOR-279745
|
Q9UIG0
|
P27361
| 0
|
phosphorylation
|
up-regulates
| 0.2
|
Wstf, a specific component of two chromatin remodeling complexes (swi/snf-type winac and iswi-type wich), was phosphorylated by the stimulation of mapk cascades in vitro and in vivo. Ser-158 residue in the wac (wstf/acf1/cbpq46) domain, located close to the n terminus of wstf, was identified as a major phosphorylation target
|
SIGNOR-188164
|
Q08379
|
P06493
| 0
|
phosphorylation
|
down-regulates
| 0.674
|
Cdc2 kinase directly phosphorylates the cis-golgi matrix protein gm130 and is required for golgi fragmentation in mitosis. Mitotic fragmentation of the golgi apparatus can be largely explained by disruption of the interaction between gm130 and the vesicle-docking protein p115. Here we identify a single serine (ser-25) in gm130 as the key phosphorylated target and cdc2 as the responsible kinase
|
SIGNOR-60281
|
P30291
|
Q9UNH5
| 0
|
dephosphorylation
|
up-regulates quantity by stabilization
| 0.545
|
In particular, we found that Cdc14A inhibits Wee1 degradation through the dephosphorylation of Ser-123 and Ser-139 residues.
|
SIGNOR-267470
|
O60260
|
Q99497
| 1
|
ubiquitination
|
down-regulates quantity by destabilization
| 0.2
|
Together, these results demonstrate that parkin selectively recognizes and ubiquitinates misfolded DJ-1 in vivo.
|
SIGNOR-278526
|
P54829
|
Q16611
| 1
|
dephosphorylation
|
up-regulates activity
| 0.2
|
In this study, we report that on apoptotic stimulation Bak undergoes dephosphorylation at tyrosine residue 108 (Y108), a critical event that is necessary but not sufficient for Bak activation, but is required both for early exposure of the occluded N-terminal domain and multimerisation.
|
SIGNOR-248542
|
P24666
|
P14618
| 1
|
dephosphorylation
|
up-regulates activity
| 0.279
|
Indeed, it is evident that LMW-PTP, hydrolyzing phosphotyrosine residues, contributes to maintain PKM2 in its active form.|We speculate that this effect is in large part due to LMW-PTP inhibition, which leads a fast PKM2 phosphorylation and inactivation.|we demonstrate that in melanoma cells the overexpression of LMW-PTP is functional to maintain PKM2 in its dephosphorylate status – the tetrameric, “full active” form - which is retained in the cytoplasm
|
SIGNOR-277134
|
Q92793
|
Q00978
| 1
|
acetylation
|
up-regulates activity
| 0.361
|
CBP was also the most effective one among the acetyltransferases tested for catalyzing IRF9 acetylation in 293T cells. [²] Figure 5 (F) K81 acetylation is required for IRF9 dimerization between the N-terminal 1-118 and the C-terminal 340-393 regions. In the left panel, Myc-DBD (1- 118) of IRF9 was cotransfected with 118-393, 118-339, or 1-393 (FL) of IRF9 in 293T cells. Anti-IRF9 (C-terminal region) precipitates were analyzed with anti-Myc or anti-IRF9. Anti-IRF9 precipitates, prepared from 293T cells cotransfected with the C-terminal fragment 118-393 of IRF9 and Myctagged DBD of different forms, were analyzed with anti-Myc or anti-IRF9 (right panel).
|
SIGNOR-217787
|
Q9C0C7
|
Q7Z6Z7
| 1
|
relocalization
|
up-regulates activity
| 0.2
|
AMBRA1 regulates mitophagy at two critical steps. Upon mitophagy stimulation, AMBRA1 mediates the HUWE1 E3 ubiquitin ligase translocation from cytosol to mitochondria (light blue). AMBRA1 acts as a cofactor for HUWE1 E3 ubiquitin ligase activity, favouring its binding to its substrate MFN2 (and maybe other OMM substrates) and targeting it to the proteasome
|
SIGNOR-272962
|
P78527
|
Q13535
| 0
|
phosphorylation
|
up-regulates
| 0.31
|
Finally, in vitro atr-mediated phosphorylation at the t2609 cluster was further confirmed by western blot analysis using phosphospecific antibodies against t2647 (fig. ?(Fig.7e),7e), suggesting that dna-pkcs could be the direct target of atr kinase.
|
SIGNOR-148722
|
P08123
|
Q8IYK4
| 0
|
glycosylation
|
up-regulates activity
| 0.4
|
Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.
|
SIGNOR-261157
|
Q16659
|
Q9UNH5
| 0
|
dephosphorylation
|
down-regulates
| 0.641
|
Using ms analysis, we identified four novel phosphorylation sites, ser684, ser688, thr698 and ser705, located at the extreme c-terminus of erk3.alanine substitution of the four c-terminal phosphorylation sites markedly decreased the half-life of erk3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase.we found that the phosphatases cdc14a and cdc14b (cdc is cell-division cycle) bind to erk3 and reverse its c-terminal phosphorylation in mitosis.
|
SIGNOR-164412
|
Q16236
|
P00441
| 1
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.408
|
BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2
|
SIGNOR-254653
|
P35568
|
P23443
| 0
|
phosphorylation
|
down-regulates quantity by destabilization
| 0.788
|
In this report, we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like growth factor 1 signaling, as a proteolytic target of the CUL7 E3 ligase in a manner that depends on mammalian target of rapamycin and the p70 S6 kinase activities.Elimination of phosphorylation at S307/S312/S527/S636/S639 renders V5-IRS-1 partially resistant to degradation by Fbw8
|
SIGNOR-236599
|
Q9BYB0
|
Q9P1A6
| 0
|
relocalization
|
up-regulates activity
| 0.2
|
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-264591
|
Q8WZ60
|
P24941
| 1
|
polyubiquitination
|
down-regulates quantity by destabilization
| 0.2
|
We confirmed the formation of ubiquitin and CDK2 by different systems and further identified the E3 ligase KLHL6 as a mediator of the ubiquitination and degradation of CDK2.
|
SIGNOR-272310
|
P19784
|
P08575
| 1
|
phosphorylation
|
up-regulates activity
| 0.434
|
Mutational analysis of CK2 consensus sites showed that the target for CK2 was in an acidic insert of 19 amino acids in the D2 domain, and Ser to Ala mutations at amino acids 965, 968, 969, and 973 abrogated CK2 phosphorylation of CD45. CK2 phosphorylation increased CD45 activity 3-fold toward phosphorylated myelin basic protein, and this increase was reversible by PP2A treatment.
|
SIGNOR-251031
|
Q9UQM7
|
Q9P0L9
| 1
|
phosphorylation
|
down-regulates activity
| 0.2
|
CaM inhibits the function of TRPP3 through promoting CaMK2's phosphorylation towards T591 on TRPP3.
|
SIGNOR-277812
|
P38435
|
Q14393
| 1
|
carboxylation
|
up-regulates activity
| 0.525
|
Thus, vitamin K acts as a cofactor for GGCX via the vitamin K cycle and exerts physiological effects through its regulation of VKDPs [29]. More than 20 VKDPs have been found. Osteocalcin promotes bone formation, and blood coagulation factors II, VII, IX, and X activate blood coagulation. Matrix Gla protein suppresses cardiovascular calcification, and brain-expressed Gas 6 promotes neural differentiation [29]. GGCX is an enzyme that converts glutamic acid (Glu) residues to Gla residues, so that the Gla-containing proteins can exert various physiological actions such as blood coagulation and bone formation.
|
SIGNOR-265923
|
O14965
|
Q5FBB7
| 1
|
phosphorylation
|
up-regulates activity
| 0.2
|
Loss of INCENP/Aurora B in Mitosis Correlates with Delocalization of MEI-S332|MEI-S332 Is Phosphorylated by Aurora B In Vitro|Of these, MEI-S332S124,125,126A was a poor substrate for Aurora B kinase in vitro
|
SIGNOR-252046
|
P63000
|
Q7Z6B7
| 0
|
gtpase-activating protein
|
down-regulates activity
| 0.56
|
We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).
|
SIGNOR-260515
|
P52564
|
Q13233
| 0
|
phosphorylation
|
up-regulates
| 0.454
|
Both wild type and kinase-inactive mutant rip immunoprecipitates can active mkk6 in vitrohe sapks are activated by at least two meks, sapk/erk kinase-1 (sek1, also called mapk-kinase (mkk)) and mkk7
|
SIGNOR-59679
|
P06493
|
P33316-2
| 1
|
phosphorylation
|
up-regulates quantity
| 0.386
|
DUTPase Is Phosphorylated at a Consensus Cyclin-dependent Protein Kinase Site: in Vitro Phosphorylation of Ser-11 by p34cdc2. It is conceivable that the exclusive phosphorylation of DUT-N may play a role in nuclear targeting of this protein. Taken a step further, Ser-11 may confer the ability of DUT-N to localize in specific regions of the nucleus where the dUTPase function is required. The Ser-11 Ala mutant should aid in the testing of these hypotheses.
|
SIGNOR-262693
|
P45984
|
P50616
| 1
|
phosphorylation
|
down-regulates
| 0.34
|
Biochemical analyses have then shown that erk mapk (erk2) and jnk/sapk (jnk2) bind to and phosphorylate tob in vitro.
|
SIGNOR-91067
|
O14965
|
P14635
| 1
|
phosphorylation
|
up-regulates activity
| 0.576
|
A second wave of Cyclin B1-CDK1 phosphorylation by AurA occurs in late prophase.|Simultaneously, AurA activates and targets the Cyclin B1-CDK1 complex at centrosomes [ xref ].
|
SIGNOR-280186
|
P06241
|
P31995
| 1
|
phosphorylation
|
up-regulates activity
| 0.2
|
Fyn and Blk definitely phosphorylate Y-282 in the ITAM of FcgRIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addition to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation
|
SIGNOR-262677
|
Q14790
|
P55210
| 1
|
cleavage
|
up-regulates
| 0.742
|
Casp8 can activate downstream caspases like caspase-6, and caspase-7 by directly cleaving them.
|
SIGNOR-58118
|
P17612
|
Q01970
| 1
|
phosphorylation
|
down-regulates
| 0.26
|
These data indicate that pkc and pka act similarly in that they inhibit galpha(q)-stimulated plcbeta(3) as a result of phosphorylation of ser(1105).
|
SIGNOR-79148
|
Q03112
|
P15976
| 1
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.319
|
We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2
|
SIGNOR-266061
|
Q16566
|
P49593
| 0
|
dephosphorylation
|
down-regulates activity
| 0.348
|
Calmodulin-dependent protein kinase phosphatase (CaMKP) dephosphorylates and concomitantly deactivates multifunctional Ca(2+)/calmodulin-dependent protein kinases , such as CaMKI, CaMKII, and CaMKIV.
|
SIGNOR-277157
|
Q9UD71
|
P19784
| 0
|
phosphorylation
|
up-regulates activity
| 0.375
|
Study of [Plphosphate release during manual Edman degradation confirmed that the phosphorylated residues in rat DARPP-32 were Ser45 and Ser102. | Phosphorylation by casein kinase II did not affect the potency of DARPP-32 as an inhibitor of protein phosphatase-1, which depended only on phosphorylation of Thr34 by cAMP-dependent protein kinase. However, phosphorylation of DARPP-32 by casein kinase II facilitated phosphorylation of Thr34 by cAMP-dependent protein kinase
|
SIGNOR-251018
|
P57078
|
Q13490
| 0
|
polyubiquitination
|
up-regulates activity
| 0.355
|
CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.Lysine residues K51 and K145 of RIP4 are critical for cIAP1-mediated ubiquitination and NF-kB activation.
|
SIGNOR-272708
|
P09429
|
Q16566
| 0
|
phosphorylation
|
up-regulates activity
| 0.285
|
Collectively, our results demonstrate that CaMKIV promotes the nucleocytoplasmic shuttling of HMGB1 and suggest that the process may be mediated through CaMKIV-dependent serine phosphorylation of HMGB1.
|
SIGNOR-278510
|
P28482
|
P50616
| 1
|
phosphorylation
|
down-regulates
| 0.354
|
Tob is rapidly phosphorylated at ser 152, ser 154, and ser 164 by erk1 and erk2 upon growth-factor stimulation.
|
SIGNOR-88720
|
P29122
|
P06213
| 1
|
cleavage
|
up-regulates activity
| 0.2
|
Here we demonstrate that the two IR isoforms are similarly cleaved by furin, but when this furin-dependent maturation is inefficient, IR proforms move to the cell surface where the proprotein convertase PACE4 selectively supports IRB maturation.
|
SIGNOR-260366
|
P39900
|
P00748
| 1
|
cleavage
|
down-regulates quantity by destabilization
| 0.33
|
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-263611
|
P27361
|
Q15418
| 1
|
phosphorylation
|
up-regulates activity
| 0.718
|
Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity.Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3.
|
SIGNOR-102648
|
P41091
|
Q9UI10
| 0
|
guanine nucleotide exchange factor
|
up-regulates activity
| 0.698
|
EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.
|
SIGNOR-269137
|
P04637
|
Q9HCM9
| 0
|
ubiquitination
|
down-regulates quantity by destabilization
| 0.351
|
Furthermore, we show here that the Trim39 can directly bind and ubiquitylate p53 in vitro and in vivo, leading to p53 degradation.
|
SIGNOR-272020
|
P51812
|
O15297
| 0
|
dephosphorylation
|
down-regulates activity
| 0.361
|
RSK2 (p90 ribosomal S6 kinase 2) is activated via the ERK (extracellular-signal-regulated kinase) pathway by phosphorylation on four sites: Ser227 in the activation loop of the N-terminal kinase domain, Ser369 in the linker, Ser386 in the hydrophobic motif and Thr577 in the C-terminal kinase domain of RSK2. In the present study, we demonstrate that RSK2 is associated in vivo with PP2Cdelta (protein phosphatase 2Cdelta). In epidermal growth factorstimulated cells, RSK2 is partially dephosphorylated on all four sites in an Mn2+-dependent manner, leading to reduced protein kinase activity
|
SIGNOR-248322
|
Q92565
|
P62834
| 1
|
guanine nucleotide exchange factor
|
up-regulates activity
| 0.648
|
We found here that cAMP-dependent activation of Epac1 and Rap1 but not PKA is able to activate CaMKI to mediate Ser47 (S47) phosphorylation in GCM1. Epac1 and Epac2 proteins were identified as cAMP-binding proteins with guanine nucleotide exchange factor (GEF) activities for the small GTPases, Rap1 and Rap2
|
SIGNOR-262682
|
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