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Q03468
Q96FI4
1
binding
up-regulates activity
0.344
CSB stimulates NEIL1 incision activity in vitro, and CSB and NEIL1 co-immunoprecipitate and co-localize in HeLa cells.
SIGNOR-251931
Q05655
P61978
1
phosphorylation
down-regulates
0.344
Ser302 is a major k protein site phosphorylated by pkcdelta in vitrothe ability of pkc_ to inducibly bind and phosphorylate k protein may serve not only to alter the activity of k protein itself, but k protein may also provide an avenue for pkc_ to engage in a cross-talk with other k protein molecular partners in response to specific changes in the extracellular environment
SIGNOR-67515
Q9UKA1
Q9BQ15
1
binding
down-regulates quantity by destabilization
0.344
Here, we report that hSSB1 is the bona fide substrate for an Fbxl5-containing SCF (Skp1-Cul1-F box) E3 ligase. Fbxl5 interacts with and targets hSSB1 for ubiquitination and degradation, which could be prevented by ATM-mediated hSSB1 T117 phosphorylation.
SIGNOR-271655
P53350
Q9Y5T5
1
phosphorylation
up-regulates activity
0.344
Plk1 phosphorylates and activates Usp16. In vitro phosphorylation of Usp16 with single (S330A, S386A, or S486A) or collective 3A (S330A/S386A/S486A) mutation showed that Plk1 phosphorylated Usp16 at all three sites (Fig. S2 D).
SIGNOR-274015
O75582
Q92934
1
phosphorylation
down-regulates activity
0.344
Phosphorylation of Bad at Ser112 in response to growth factors or cytokines is generally linked to cell survival. Knockdown of MSK1 suppressed Bad phosphorylation after calcium ionophore A23187 treatment in neuronal cells
SIGNOR-262990
Q9Y613
P60709
1
binding
up-regulates quantity by stabilization
0.344
Fhos, a mammalian formin, directly binds to F-actin via a region N-terminal to the FH1 domain and forms a homotypic complex via the FH2 domain to promote actin fiber formation
SIGNOR-276613
P78368
Q13330
1
phosphorylation
up-regulates activity
0.344
CKI-gamma2 could further potentiate the ER corepressive function of metastasis-associated protein-1 short form.|These findings identified metastasis-associated protein-1 short form as a target of CKI-gamma2, and provided new evidence to suggest that CKI-gamma2 phosphorylates and modulates the functions of metastasis-associated protein-1 short form, and that these extranuclear effects of estrogen might have important implications in regulating the functions of metastasis-associated protein-1 short form in human mammary epithelial and cancer cells.
SIGNOR-280236
P68400
Q13351
1
phosphorylation
up-regulates activity
0.344
Regulation of erythroid Krƒppel-like factor (EKLF) transcriptional activity by phosphorylation of a protein kinase casein kinase II site within its interaction domain. the transactivation capability of EKLF is augmented by co-transfection of CKIIalpha. in vitro assays demonstrate that CKIIalpha interacts with EKLF, and that the EKLF interaction domain is phosphorylated by CKII only at Thr-41
SIGNOR-241361
O14672
P04626
1
cleavage
up-regulates activity
0.344
The ADAM proteases are best known for their role in shedding the extracellular domain of transmembrane proteins. Among the transmembrane proteins shed by ADAM10 are notch, HER2, E-cadherin, CD44, L1 and the EGFR ligands, EGF and betacellulin.
SIGNOR-259845
P50406
P50148
1
binding
up-regulates activity
0.344
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-257340
P11940
Q12986
2
binding
up-regulates activity
0.344
We identifiednew protein partners of NFX1-123, including several cytoplasmic poly(A) binding proteins (PABPCs) thatinteracted with NFX1-123 through its N-terminal PAM2 motif. Central to our findings were our observations that PABPCs copurify with NFX1-123, that a PAM2 motif is present in NFX1, and this motif and the PABPCs are important in the enhancement of hTERT activity by NFX1-123.
SIGNOR-261052
Q9NPG1
P61586
1
binding
up-regulates activity
0.344
Upon ligand binding, non-canonical wnt signaling controls tissue polarity and cell movement through the activation of rhoa, c-jun n-terminal kinase (jnk), and nemo-like kinase (nlk) signaling cascades.
SIGNOR-167865
P51610
Q13105
1
binding
down-regulates activity
0.344
We show here that HCF-1 directly binds to the Myc-interacting protein Miz-1. HCF-1 Represses Gal4-Miz-1-mediated Transcriptional Activation
SIGNOR-223590
P23467
P06213
1
dephosphorylation
down-regulates
0.344
Identification of tyrosine phosphatases that dephosphorylate the insulin receptor.
SIGNOR-75997
P68400
P09629
1
phosphorylation
down-regulates activity
0.344
Thus, we concluded that CKII can phosphorylate HOXB7 in vitro and that this phosphorylation occurs at both of the CKII target sites, S133 and T204. | Wild-type HOXB7 inhibited the differentiation of 32D cells, whereas mutations in the Pbx-binding pentapeptide motif or the DNA-binding homeodomain, as well as internal deletions of the N-terminal unique region, blocked this effect. Interestingly, mutations eliminating two target sites for casein kinase II, the glutamate-rich C terminus, or the first 14 amino acids of HOXB7, led to enhanced 32D differentiation.
SIGNOR-250896
Q05209
Q14161
1
dephosphorylation
down-regulates
0.344
Conversely, a gfp-pkl phosphorylation mutant, y286/392/592f (gfp-pkl triple yf) (brown et al., 2005), was not phosphorylated during adhesion and the addition of ptp-pest had no effect, suggesting one or more of these tyrosine residues are dephosphorylated by ptppest. Taken together, these data strongly suggest pkl as a direct substrate for ptp-pest.
SIGNOR-142719
P00519
P40692
1
phosphorylation
up-regulates quantity by stabilization
0.344
We also observed phosphorylation of MLH1 by ABL1 in an in vitro kinase assay with purified recombinant ABL1 and MLH1, confirming there is a direct phosphorylation between ABL1 and the MLH1 component of the MLH1-PMS2 heterodimer.|we propose that ABL1 prevents MLH1 from being targeted for degradation by the chaperone Hsp70 and that in the absence of ABL1 activity at least a portion of MLH1 is degraded.
SIGNOR-279581
O00141
P15056
1
phosphorylation
down-regulates activity
0.344
Serum- and glucocorticoid-inducible kinase SGK phosphorylates and negatively regulates B-Raf.|We observed that SGK inhibits B-Raf activity.
SIGNOR-279110
P06493
Q14807
1
phosphorylation
up-regulates activity
0.344
Cdc2-mediated phosphorylation of kid controls its distribution to spindle and chromosomes. We identify ser427 and thr463 as m phase-specific phosphorylation sites and cdc2-cyclin b as a thr463 kinase. Kid with a thr463 to alanine mutation fails to be localized on chromosomes and is only detected along spindles, although it retains the ability to bind dna or chromosomes
SIGNOR-100964
O00192
P33151
1
binding
up-regulates quantity by stabilization
0.344
To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member.
SIGNOR-252129
Q7KZI7
Q8WUI4
1
phosphorylation
down-regulates
0.344
We further show that emk and c-tak1 phosphorylate class iia hdacs on one of their multiple 14-3-3 binding sites and alter their subcellular localization and repressive function
SIGNOR-149583
P68400
P35638
1
phosphorylation
down-regulates activity
0.344
CHOP transcription factor phosphorylation by casein kinase 2 inhibits transcriptional activation. | The serine to alanine substituted site CHOP mutant was not phosphorylated by CK2, indicating that serines 14–15 and 30–31 of CHOP are the CK2 phosphoacceptor sites
SIGNOR-250850
Q12986
P11940
2
binding
up-regulates activity
0.344
NFX1-123 augments the activation of hTERT expression through interactions with PABPCs
SIGNOR-226011
O00311
Q99459
1
phosphorylation
down-regulates activity
0.344
During SPOC, Dbf4 binds to Cdc5 and promotes Cdc7-mediated phosphorylation of Cdc5, which then presumably prevents Cdc5 from recognizing its substrates in the MEN pathway .
SIGNOR-280203
Q9H0H3
P53396
1
binding
down-regulates quantity by destabilization
0.344
Here, we found that CUL3 interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate and degrade ACLY in cells. 
SIGNOR-272333
Q5T0W9
P48729
1
binding
up-regulates quantity
0.344
We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.
SIGNOR-273746
P23443
O94763
1
phosphorylation
down-regulates activity
0.344
Here we report that the prefoldin chaperone URI represents a mitochondrial substrate of S6K1. In growth factor-deprived or rapamycin-treated cells, URI forms stable complexes with protein phosphatase (PP)1gamma at mitochondria, thereby inhibiting the activity of the bound enzyme. Growth factor stimulation induces disassembly of URI/PP1gamma complexes through S6K1-mediated phosphorylation of URI at serine 371.
SIGNOR-262943
Q14833
P63092
1
binding
up-regulates activity
0.344
MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.
SIGNOR-264082
P27216
P46934
1
relocalization
up-regulates quantity
0.344
Annexin XIII has two known isoforms, a and b, that are apically localized, although XIIIa is also found in the basolateral compartment. In vitro binding and coprecipitation experiments showed that the Nedd4-C2 domain interacts with both annexin XIIIa and b in the presence of Ca2+, and the interaction is direct and optimal at 1 μM Ca2+.These results suggest that the apical membrane localization of Nedd4 is mediated by an association of its C2 domain with the apically targeted annexin XIIIb.
SIGNOR-272571
Q13043
Q96EB6
1
phosphorylation
down-regulates activity
0.344
We found that MST1 increases p53 acetylation and transactivation by inhibiting the deacetylation of Sirtuin 1 (Sirt1) and its interaction with p53 and that Sirt1 can be phosphorylated by MST1 leading to the inhibition of Sirt1 activity.
SIGNOR-279574
Q9Y4K3
P01106
1
ubiquitination
down-regulates activity
0.344
We posited that TRAF6 ubiquitination of MYC at K148 prevents its acetylation, which results in diminished MYC activity ( xref ).
SIGNOR-278563
P62877
P03372
1
ubiquitination
down-regulates quantity by destabilization
0.344
I3C-dependent activation of the aryl hydrocarbon receptor (AhR) initiates Rbx-1 E3 ligase-mediated ubiquitination and proteasomal degradation of ERalpha protein.
SIGNOR-271434
P17252
Q13976
1
phosphorylation
up-regulates
0.344
Antibodies generated against phosphorylated threonine 58 were used to demonstrate phosphorylation in response to pma treatment of the cells with kinetics similar to vasodilator-stimulated phosphoprotein phosphorylation. A phospho-mimetic mutation at this site (t58e) generated a partially activated pkg that was more sensitive to cgmp levels. A phospho- mutation (t58a) revealed that this residue is important but not sufficient for pkg activation by pkc.
SIGNOR-98803
Q9H0B6
Q9BQS8
1
binding
up-regulates activity
0.344
Interestingly, bead capture assays indicated that the middle part of FYCO1 (residues 585–1233) interacts directly with the KLC2 light chain of kinesin 1 (Fig. 3a and Extended Data Fig. 7a, b). Residues 735–773 of FYCO1 were found to be necessary for its kinesin-1 binding (Fig. 3c and Extended Data Fig. 7b, c), and FYCO1(Δ735–773)-positive LEs failed to translocate to the cell periphery (Extended Data Fig. 7e).
SIGNOR-260599
P06241
Q04759
1
phosphorylation
up-regulates
0.344
Further indications of direct interaction are that p59fyn potentiates ?PKC Catalytic activity and that ?PKC Is a substrate for tyrosine phosphorylation by p59fyn.
SIGNOR-68798
P19474
Q9C035
1
monoubiquitination
up-regulates quantity
0.344
Here, we show that TRIM5alpha functions as a RING-finger-type E3 ubiquitin ligase both in vitro and in vivo and ubiquitinates itself in cooperation with the E2 ubiquitin-conjugating enzyme UbcH5B. Thus, the ubiquitination of TRIM5alpha is catalyzed by itself and Ro52. Unexpectedly, although TRIM5alpha is ubiquitinated, our results have revealed that the proteasome inhibitors MG115 and MG132 do not stabilize it in HeLa cells, suggesting that the ubiquitination of TRIM5alpha does not lead to proteasomal degradation. Importantly, TRIM5alpha is clearly conjugated by a single ubiquitin molecule (monoubiquitination). Our monoubiquitin-fusion assay suggests that monoubiquitination is a signal for TRIM5alpha to translocate from cytoplasmic bodies to the cytoplasm.
SIGNOR-271672
Q01973
P21860
1
phosphorylation
up-regulates activity
0.343
Here we show that NKX2-1 induces the expression of the receptor tyrosine kinase-like orphan receptor 1 (ROR1), which in turn sustains a favorable balance between prosurvival PI3K-AKT and pro-apoptotic p38 signaling, in part through ROR1 kinase-dependent c-Src activation, as well as kinase activity-independent sustainment of the EGFR-ERBB3 association, ERBB3 phosphorylation, and consequential PI3K activation.|ROR1 knockdown decreased phosphorylations of ERBB3, c-Src, and AKT in NKX2-1 + / ROR1 + NCI-H1975, SK-LC-5, and NCI-H358 cells.
SIGNOR-279279
P06493
Q13501
1
phosphorylation
up-regulates
0.343
Here we show that cdk1 phosphorylates p62 in vitro and in vivo at t269 and s272, which is necessary for the maintenance of appropriate cyclin b1 levels and the levels of cdk1 activity necessary to allow cells to properly enter and exit mitosis.
SIGNOR-169012
P53350
O14920
1
phosphorylation
down-regulates
0.343
Plk1 phosphorylates serines 733, 740, and 750 in the gammabd of ikkbeta in vitro. Phosphorylating gammabd with plk1 decreased its affinity for ikkgamma
SIGNOR-181802
P00519
P42224
1
phosphorylation
up-regulates activity
0.343
Our study unexpectedly found that c-Abl, another kinase other than JAKs, also contributes to STAT1 Y701 phosphorylation independently (XREF_FIG).|reported that c-Abl, but not Arg, could induce neuronal loss by prompting STAT1 activation and interferon production.
SIGNOR-279491
Q9UNE7
Q99717
1
ubiquitination
down-regulates
0.343
In ad-dition, some proteins (e.g. Chip, carboxyl terminus of hsc70-interacting protein) inhibit the signaling activi-ties of smad1/5 by recruiting smad1/5 from the functional r-/co-smad complex and further pro-moting the ubiquitination and degradation of smad1/5 in a chaperone-independent manne
SIGNOR-195690
O60674
Q9UGK3
1
phosphorylation
up-regulates activity
0.343
To examine this possibility, STAP-2 was co-transfected with constitutively active tyrosine kinases in HEK-293 cells. STAP-2 was strongly phosphorylated by various tyrosine kinases, including v-Src (Fig.2 A-a), a JAK2 tyrosine kinase |On the other hand, the phosphorylation levels of Y22F, Y310F, and Y322F by GST-JH1 were reduced to 80€“60% of the levels of wild-type STAP-2, which suggests that these three are potential phosphorylation sites by activated JAK2.
SIGNOR-249372
Q13043
P00519
2
phosphorylation
down-regulates
0.343
Here, we identify clk1, clk4, mst1, mst2 and ttk (also known as mps1) as novel thr735 kinases in vitro / phosphorylation of thr735 in c-abl is critical for binding to 14-3-3
SIGNOR-181060
P11229
P08754
1
binding
up-regulates activity
0.343
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-256878
Q9BZR9
O43318
1
polyubiquitination
up-regulates activity
0.343
These results suggest that TRIM8 could mediate K63-linked polyubiquitination of TAK1 at residue K158.These results suggest that TRIM8 is involved in TNFα- and IL-1β–induced NF-κB activation by mediating K63-linked TAK1 polyubiquitination and subsequent activation.
SIGNOR-271890
P41743
P50613
1
phosphorylation
up-regulates activity
0.343
PKC\u03b9 activates CDK7 to promote glucose consumption.|PKC\u03b9 phosphorylates Thr170 on CDK7 in vitro, can associate with CDK7 in cells, and is activated downstream of PI3K signaling xref , xref \u2013 xref .
SIGNOR-280088
P17612
Q15256
1
phosphorylation
down-regulates activity
0.343
The PKA phosphorylation site on PTP-SL was identified as the Ser(231) residue. treatment of COS-7 cells with PKA activators, or overexpression of the Calpha catalytic subunit of PKA, inhibited the cytoplasmic retention of ERK2 and p38alpha by wild-type PTP-SL, but not by a PTP-SL S231A mutant.‚ 
SIGNOR-250038
P19784
Q13351
1
phosphorylation
up-regulates activity
0.343
Regulation of erythroid Krppel-like factor (EKLF) transcriptional activity by phosphorylation of a protein kinase casein kinase II site within its interaction domain. the transactivation capability of EKLF is augmented by co-transfection of CKIIalpha. in vitro assays demonstrate that CKIIalpha interacts with EKLF, and that the EKLF interaction domain is phosphorylated by CKII only at Thr-41
SIGNOR-241365
O14965
Q13158
1
phosphorylation
up-regulates
0.343
Here, we report that aur-a phosphorylates s203 of the fas associated with death domain protein (fadd)phosphorylation of s203 by aur-a serves to prime fadd for plk1-mediated phosphorylation at s194
SIGNOR-176739
P54253
P12830
1
transcriptional regulation
up-regulates quantity by expression
0.343
Overexpression of the CtBP2 protein enhanced the repression activity of the E-cadherin promoter in a dose-dependent manner, whereas overexpression of ataxin-1 increased the activity of the E-cadherin promoter in a dose-dependent manner 
SIGNOR-261577
P36897
O00459
1
binding
up-regulates
0.343
These studies revealed that PI 3-kinase is associated in vivo with both TGF-_ receptor subtypes and that TGF-_1 stimulation enhances PI 3-kinase activity associated with type I TGF-_ receptor in hASM cells.
SIGNOR-227531
P31751
Q92945
1
phosphorylation
down-regulates
0.343
AKT phosphorylates the mRNA decay-promoting factor KSRP at a unique serine residue, induces its association with the multifunctional protein 14-3-3, and prevents KSRP interaction with the exoribonucleolytic complex exosome. This impairs KSRP’s ability to promote rapid mRNA decay.
SIGNOR-151220
Q18PE1
P46109
1
binding
up-regulates activity
0.343
Here, we identify two tyrosine residues in Dok-7 that are phosphorylated by Agrin stimulation, and show that two proteins, Crk and Crk-L, are recruited to these phosphorylation sites in Dok-7.
SIGNOR-273848
Q13153
P36871
1
phosphorylation
up-regulates
0.343
The signaling kinase p21-activated kinase 1 (pak1) binds to, phosphorylates and enhances the enzymatic activity of phosphoglucomutase 1 (pgm),
SIGNOR-127135
Q7Z6Z7
P15172
1
ubiquitination
down-regulates quantity
0.343
Importantly, addition of WT HUWE1 to a proteolytic reaction mixture enhanced the degradation of MyoD.|Mass-spectrometry analyses show that HUWE1 can ubiquitinate MyoD at its N-terminal residue, though the preferred sites are - at least in a cell free system - the internal lysines of the protein.
SIGNOR-278694
Q9NXA8
P54868
1
post translational modification
up-regulates activity
0.343
We demonstrate that SIRT5 regu-lates succinylation of the rate-limiting ketogenicenzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2(HMGCS2) both in vivo and in vitro.|Succinylation of Lysine Residues within the SubstrateBinding Pocket Inhibits HMGCS2 Activity|Here, we use a label-freequantitative proteomic approach to characterizethe lysine succinylome in liver mitochondria and itsregulation by the desuccinylase SIRT5
SIGNOR-267641
P17252
P19429
1
phosphorylation
up-regulates activity
0.343
In addition to the established phosphorylation sites (S22 and S23) we found that S38 and S165 were the other two main sites of phosphorylation. | Phosphorylation of S22/23A also decreased its affinity for troponin C indicating that phosphorylation of S38 and/or S165 impedes binding of troponin I to troponin C. Formation of a troponin I/troponin C complex prior to cAMP-dependent protein kinase treatment did not prevent overphosphorylation.
SIGNOR-249066
P36897
P68104
1
phosphorylation
down-regulates
0.343
Phosphorylation of eEF1A1 at Ser300 by T_R-I results in inhibition of mRNA translation
SIGNOR-167943
Q96EV8
Q9Y6W5
1
binding
up-regulates activity
0.343
Dysbindin-1, WAVE2 and Abi-1 form a complex that regulates dendritic spine formation. Although dysbindin-1, WAVE2 and Abi-1 form a ternary complex, dysbindin-1 promoted the binding of WAVE2 to Abi-1.
SIGNOR-265659
Q02750
P49841
1
phosphorylation
up-regulates activity
0.343
In vitro kinase assay was carried out using a recombinant human active mek1 and we found that gsk-3beta was phosphorylated on tyr(216) by this kinase in a dose- and time-dependent manner. Further, the pretreatment of fibroblasts with u0126 inhibited serum-induced nuclear translocation of gsk-3beta. These results suggested that mek1/2 induces tyrosine phosphorylation of gsk-3beta and this cellular event might induce nuclear translocation of gsk-3beta.
SIGNOR-236622
P00519
Q14847
1
phosphorylation
up-regulates
0.343
C-abl activation by apoptotic agents specifically promotes phosphorylation of lasp-1 at tyrosine 171, which is associated with the loss of lasp-1 localization to focal adhesions and induction of cell death. Thus, lasp-1 is a dynamic focal adhesion protein necessary for cell migration and survival in response to growth factors and ecm proteins.
SIGNOR-124719
P29350
O94916
1
dephosphorylation
down-regulates activity
0.343
We confirmed that SHP-1 is inhibitory by overexpressing it, which reduces TonEBP/OREBP transcriptional activity at 500 mosmol/kg. SHP-1 dephosphorylates TonEBP/OREBP at a known regulatory site, Y143, both in vivo and in vitro. It inhibits TonEBP/OREBP by both reducing TonEBP/OREBP nuclear localization, which is Y143 dependent, and by lowering high NaCl-induced TonEBP/OREBP transactivating activity
SIGNOR-248467
P00533
Q38SD2
1
phosphorylation
down-regulates activity
0.343
In this study, we demonstrate that EGFR regulates the kinase activity of LRRK1 via tyrosine phosphorylation and that this is required for proper endosomal trafficking of EGFR. Phosphorylation of LRRK1 at Tyr-944 results in reduced LRRK1 kinase activity.
SIGNOR-262856
P24941
P10644
1
phosphorylation
up-regulates
0.343
In this context, we have identified rialpha as a novel substrate for the g(1)/s-cyclin-dependent kinase, cdk2/cyclin e, and found that rialpha is specifically phosphorylated at the serine residue.
SIGNOR-145577
P51149
O14818
1
binding
up-regulates activity
0.343
Rab7 Forms a Complex with the Proteasome -Subunit XAPC. In this study the proteasome alpha-subunit XAPC7 (also known as PSMA7, RC6-1, and HSPC in mammals) was identified to interact specifically with Rab7 and was recruited to multivesicular late endosomes through this interaction.
SIGNOR-261303
P68400
Q02790
1
phosphorylation
down-regulates activity
0.343
Thr-143 in the hinge I region was identified as the major phosphorylation site for CK2. | Most importantly, CK2-phosphorylated FKBP52 did not bind to HSP90
SIGNOR-250865
P00519
Q13043
2
phosphorylation
up-regulates activity
0.343
In the present study, we demonstrate that the protein kinase c-Abl phosphorylates MST1 at Y433, which triggers the stabilization and activation of MST1.
SIGNOR-260927
P27361
Q01860
1
phosphorylation
down-regulates
0.343
Phosphorylation of this site downregulates nanog, sox2, rex1 and upregulates bmp4, gata6, ddlx5.
SIGNOR-192101
P12931
P16662
1
phosphorylation
up-regulates
0.343
Overexpression of regular or active src, but not dominant-negative src, in 2b7-transfected cos-1 cells increased 2b7 activity and phospho-y438-2b7 by 50%
SIGNOR-184613
P06241
Q8TDQ1
1
phosphorylation
up-regulates activity
0.343
Y236 (YVTM) and Y263 (YCNM) fit with the consensus motif reported to bind the p85α regulatory subunit of PI3K (16). |The association between IREM-1 and p85α was only perceived in the presence of c-Fyn, suggesting that tyrosine phosphorylation of IREM-1 cytoplasmic tail of IREM-1 was required for the interaction.
SIGNOR-275620
Q00341
P07333
1
transcriptional regulation
down-regulates quantity by repression
0.342
Vigilin (Vgl1) is essential for heterochromatin formation, chromosome segregation, and mRNA stability and is associated with autism spectrum disorders and cancer: vigilin, for example, can suppress proto-oncogene c-fms expression in breast cancer.
SIGNOR-266696
P68400
P29590
1
phosphorylation
down-regulates
0.342
Here we show that ck2 regulates pml protein levels by promoting its ubiquitin-mediated degradation dependent on direct phosphorylation at ser517.
SIGNOR-148306
Q13131
P04049
1
phosphorylation
down-regulates
0.342
Ampk also phosphorylated full-length, kinase-defective raf-1 (k375m) to generate two [32p]phosphopeptides, one co-migrating with synthetic tryptic peptide containing phospho-ser621 and the other with phospho-ser259. The catalytic subunit of PKA also phosphorylated Ser621 in vitro, while its overexpression in intact cells resulted in increased phosphorylation of Ser621 and decreased activity of Raf-1. These results suggest that phosphorylation of Ser621 inactivates Raf-1, but do not prove that PKA is responsible for this in vivo.
SIGNOR-47148
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
P68400
P06127
1
phosphorylation
up-regulates
0.342
In this study, we use jurkat t cell transfectants of cd5 cytoplasmic tail mutants to reveal phosphorylation sites relevant to signal transduction. Our results show that casein kinase ii (ckii) is responsible for the constitutive phosphorylation of cd5 molecules at a cluster of three serine residues located at the extreme c terminus (s458, s459, and s461)
SIGNOR-62311
Q9Y297
P47736
1
ubiquitination
down-regulates
0.342
Here, we demonstrated that rap1gap is ubiquitinated and degraded through proteasome pathway in mitosis. Proteolysis of rap1gap requires the plk1 kinase and _-trcp ubiquitin ligase complex.
SIGNOR-203548
Q8TDX7
P54274
1
phosphorylation
up-regulates activity
0.342
Using KR-TRF2 to induce telomeric DNA damage, we found that TRF1 degradation was also exacerbated when ATM was inhibited after damage induction (55.2% of mock treated cells) (XREF_FIG), indicating that the ATM signal pathway is required for Nek7 mediated TRF1 stabilization.|We show that Nek7 phosphorylates TRF1 at Ser114 and in turn maintains stability of the shelterin complex at telomeres.
SIGNOR-278447
P09874
P09884
1
binding
up-regulates activity
0.342
We provide evidence that in proliferating cells: (i) PARP is physically associated with the catalytic subunit of the DNA polymerase α–primase tetramer, an association confirmed by confocal microscopy, demonstrating that both enzymes are co-localized at the nuclear periphery of HeLa cells.|(iii) PARP-deficient cells derived from PARP knock-out mice exhibited reduced DNA polymerase activity,
SIGNOR-261270
Q16236
P08263
1
transcriptional regulation
up-regulates quantity by expression
0.342
In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs).
SIGNOR-256278
P12931
Q7Z3C6
1
phosphorylation
up-regulates activity
0.342
Src phosphorylates mATG9 at Tyr8 to maintain its endocytic and constitutive trafficking in unstressed conditions. In response to starvation, phosphorylation of mATG9 at Tyr8 by Src and at Ser14 by ULK1 functionally cooperate to promote interactions between mATG9 and the AP1/2 complex, leading to redistribution of mATG9 from the plasma membrane and juxta-nuclear region to the peripheral pool for autophagy initiation.
SIGNOR-266367
P24941
P26358
1
phosphorylation
up-regulates
0.342
We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5
SIGNOR-173681
Q05655
P49840
1
phosphorylation
down-regulates
0.342
Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.
SIGNOR-115722
Q15475
P15311
1
transcriptional regulation
up-regulates quantity
0.342
We now show that the gene encoding Ezrin is a direct transcriptional target of Six1.
SIGNOR-259374
P50552
P31939
1
phosphorylation
up-regulates activity
0.342
ATIC and VASP phosphorylation is dependent on NPM-ALK kinase activity. 
SIGNOR-276172
P52564
Q14765
1
phosphorylation
up-regulates activity
0.342
MKK6, phosphorylate STAT4 on serine 721. IL-12 induces STAT4 phosphorylation on serine 721 and that mutation of serine 721 interferes with STAT4 transcriptional activity.
SIGNOR-251425
P41743
P15311
1
phosphorylation
up-regulates
0.342
Pkciota phosphorylated ezrin on t567 in vitro, and in sf9 cells that do not activate human ezrin. we conclude that, although other molecular mechanisms contribute to ezrin activation, apically localized phosphorylation by pkciota is essential for the activation and normal distribution of ezrin at the early stages of intestinal epithelial cell differentiation.
SIGNOR-160855
Q96LB2
P50148
1
binding
up-regulates activity
0.342
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-257384
Q09472
Q10571
2
binding
up-regulates
0.342
Our results indicate that mn1 is a transcription coactivator rather than a sequence-specific transcription factor, and that it may stimulate rar/rxr-mediated transcription through interaction with p160 and p300.
SIGNOR-97899
P24941
Q02535
1
phosphorylation
down-regulates
0.342
We now show that an analogous cell-cycle-regulated phosphorylation of id3 alters the specificity of id3 for abrogating both e-box-dependent bhlh homo- or heterodimer complex formation in vitro and e-box-dependent reporter gene function in vivo._
SIGNOR-53306
Q10571
Q09472
2
binding
up-regulates activity
0.342
Taken together, our results indicate that MN1 is a transcription coactivator rather than a sequence-specific transcription factor, and that it may stimulate RAR/RXR-mediated transcription through interaction with p160 and p300.
SIGNOR-256020
Q14678
Q9UQB8
1
binding
down-regulates activity
0.342
In this study, we report that Kank disrupts the function of active Rac1 through IRSp53. The binding between IRSp53 and Kank inhibits the association of active Rac1 with IRSp53 rather than the association of active cdc42 with IRSp53. Kank inhibits the formation of lamellipodia and membrane ruffles induced by active Rac1 in NIH3T3 cells. Kank interacts with IRSp53 through their coiled-coil domains. Kank affected the interaction between IRSp53 and Rac1 and partially affected that between IRSp53 and cdc42 (Fig. 3).
SIGNOR-265553
O15379
O15105
1
binding
up-regulates
0.342
We show here that smad7 can form a complex with endogenous histone deacetylase proteins hdac-1 and hdac-3 in nih 3t3 mouse fibroblast cells
SIGNOR-199967
P55210
P49768
1
cleavage
up-regulates activity
0.342
Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.
SIGNOR-261757
Q9BZE9
Q9H867
1
binding
up-regulates
0.342
In the case of vcp, methylation by mettl21d was stimulated by the addition of the ubx cofactor aspscr1, which we show directly interacts with the methyltransferase.
SIGNOR-200572
Q96L73
P10163
1
transcriptional regulation
up-regulates quantity by expression
0.342
We here demonstrate that NSD1 could bind to the promoter regions of PRB4 and activate promoter activity by reducing the binding of H3K27me2 and increasing the binding of H3K36me2 on PRB4 promoter.
SIGNOR-268459
P10586
P31749
1
dephosphorylation
down-regulates
0.342
Knock-down of lar by the l3 sirna probe markedly inhibited the insulin-stimulated increase in the phosphorylation of protein kinase b (pkb, also called akt) on serine 473 by >90%
SIGNOR-137246
O43293
Q00987
1
phosphorylation
up-regulates quantity by stabilization
0.342
Zip kinase was able to phosphorylate mdm2 at ser166, a site previously reported to be modified by akt kinase, thus demonstrating that zip kinase is a bona fide mdm2-binding protein.
SIGNOR-123159
Q07912
O00308
1
phosphorylation
up-regulates activity
0.342
ACK1 phosphorylates WWP2 at the 2, 3-linker and partially activates the ubiquitination ligase activity.|Activation of E3 ubiquitin ligase WWP2 by non-receptor tyrosine kinase ACK1.
SIGNOR-279302
Q12772
Q7KZF4
1
transcriptional regulation
up-regulates quantity by expression
0.342
These findings reveal that SREBP-2 and SREBP-1 bind to specific sites in SND1 promoter and regulate SND1 transcription in opposite ways; it is induced by SREBP-2 activating conditions and repressed by SREBP-1 overexpression.
SIGNOR-259136
P08253
P98164
1
binding
up-regulates quantity
0.342
We show that megalin/LRP-2 acts as an endocytic receptor for proMMP-2:TIMP-2 complex. We found that RAP, an antagonist of the LDL receptor family18, competed with binding of proMMP-2:TIMP-2 complex onto rat BN16 epithelial cells.
SIGNOR-265255