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P17010
P09467
1
transcriptional regulation
down-regulates quantity by repression
0.2
For instance, nucleophosmin (NPM1) and zinc-finger protein X-linked (ZFX) bind to the E-box and ZFX binding site on the FBP1 promoter, respectively, and restrain FBP1 expression to facilitate aerobic glycolysis in PDAC and melanoma
SIGNOR-267595
O75604
P36897
1
deubiquitination
up-regulates activity
0.2
Here, we report the role of USP2a in promoting metastasis by facilitating TGF-β-triggered signaling. USP2a interacts with TGFBR1 and TGFBR2 upon TGF-β stimulation and removes K33-linked polyubiquitin chains from Lys502 of TGFBR1, promoting the recruitment of SMAD2/3. Simultaneously, TGFBR2 phosphorylates Ser207/Ser225 of USP2a, leading to the disassociation of SMAD2/3 from TGFBR1.
SIGNOR-273605
Q9HCK8
Q9HD90
1
transcriptional regulation
down-regulates quantity
0.2
Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells
SIGNOR-268918
P24941
Q8WVD3
1
phosphorylation
up-regulates activity
0.2
Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner.Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner.
SIGNOR-277831
O14965
O96028
1
phosphorylation
up-regulates quantity by stabilization
0.2
Mechanistically, Aurora A phosphorylated NSD2 at S56 residue to protect the protein from cleavage and degradation, thus methylation of Aurora A and phosphorylation of NSD2 bilaterally formed a positive regulating loop.
SIGNOR-275512
Q16512
P36871
1
phosphorylation
up-regulates
0.2
Pak1-mediated phosphorylation of pgm selectively on threonine 466 significantly increased pgm enzymatic activity
SIGNOR-128722
Q96M94
Q15173
1
binding
down-regulates quantity by destabilization
0.2
Here, we report that KLHL15-Cul3 specifically targets B'β to promote turnover of the PP2A subunit by ubiquitylation and proteasomal degradation. We mapped KLHL15 residues critical for homodimerization as well as interaction with Cul3 and B'β.
SIGNOR-272017
P68400
P52907
1
phosphorylation
up-regulates
0.2
We demonstrate that ser9 of cpalpha is phosphorylated by protein kinase ck2 in vitro, that cpalpha is phosphorylated in vivo. Finally, we demonstrate that ckip-1 and ck2 inhibit the activity of actin capping protein at the barbed ends of actin filaments.
SIGNOR-135422
P67870
P18848
1
phosphorylation
down-regulates quantity by destabilization
0.2
By using mutants of ATF4 we identified serine 215 as the main CK2 phosphorylation site. The ATF4 S215A mutant turned out to be more stable than the wild-type form. 
SIGNOR-276424
Q00526
Q5TKA1
1
phosphorylation
up-regulates
0.2
In this report, we demonstrate that cyclin e1/cdk3 phosphorylates lin-9 on thr-96. Mutating thr-96 to alanine inhibits activation of cyclins a2 and b1 promoters, whereas a phosphomimetic asp mutant strongly activates their promoters and triggers accelerated entry into g2/m phase in 293t cells.
SIGNOR-204529
Q5XPI4
P83916
1
polyubiquitination
down-regulates quantity by destabilization
0.2
In the present study, we report that HP1α and β undergo proteasomal degradation in lamin A/C knock-down cells and show by ectopic expression, RNAi and binding studies that the RING finger ubiquitin ligase RNF123 is directly involved in HP1 degradation.
SIGNOR-272034
P19484
O75807
1
transcriptional regulation
up-regulates quantity by expression
0.2
We found that the main regulator of the starvation-induced transcriptional program, TFEB, counteracts protein synthesis inhibition by directly activating expression of GADD34, a component of the protein phosphatase 1 complex that dephosphorylates eIF2α.
SIGNOR-276789
Q15418
Q96RK0
1
phosphorylation
down-regulates
0.2
Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3)
SIGNOR-169883
Q8NG31
O60566
1
binding
up-regulates
0.2
Association of the amino and middle domain of blinkin with the tpr domains in the amino termini of bubr1 and bub1 is essential for bubr1 and bub1 to execute their distinct mitotic functions
SIGNOR-158894
Q9UHD2
Q12834
1
phosphorylation
down-regulates activity
0.2
It was found that TBK1 phosphorylates both Cdc20 as well as Cdh1 (Figure 2F).
SIGNOR-279766
P31260
Q15746
1
transcriptional regulation
up-regulates quantity by expression
0.2
Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively
SIGNOR-261643
P62136
Q70Z35
1
dephosphorylation
up-regulates activity
0.2
PREX2 is dephosphorylated by PP1α and PP2A.PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ.
SIGNOR-277183
Q86YJ5
Q9BV40
1
ubiquitination
down-regulates quantity by destabilization
0.2
MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets. 
SIGNOR-271531
P08238
Q75N03
1
binding
up-regulates quantity
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. Hsp90 participates in the correct folding of its client proteins, allowing them to maintain their stability and activity.
SIGNOR-271475
P16104
Q14676
1
binding
up-regulates
0.2
Here, we demonstrate that mammalian mdc1/nfbd1 directly binds to phospho-h2ax (gammah2ax) by specifically interacting with the phosphoepitope at the gammah2ax carboxyl terminus.
SIGNOR-143377
Q8IYM1
Q14141
1
binding
down-regulates
0.2
Sept12 interacts with sept6 and this interaction alters the filament structure of sept6 in hela cells.
SIGNOR-159537
Q9UPS6
P68431
1
methylation
down-regulates activity
0.2
SETD1B encodes a lysine-specific methyltransferase that assists in transcriptional activation of genes by depositing H3K4 methyl marks.
SIGNOR-265576
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
Q96LB1
P63096
1
binding
up-regulates activity
0.2
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- 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-257059
P00558
O15530
2
phosphorylation
up-regulates activity
0.2
PGK1 is an important enzyme in the metabolic glycolysis pathway, but PGK1 also phosphorylates and activates PDK1 through its protein kinase activity ( xref ).|PGK1 is an important enzyme in the metabolic glycolysis pathway, but PGK1 also phosphorylates and activates PDK1 through its protein kinase activity.
SIGNOR-280064
P17612
P16144
1
phosphorylation
down-regulates
0.2
Additionally, we show that s1360 and s1364 of beta4 are the only residues phosphorylated by pkc and pka in cells, respectivelywe have defined three regions on beta4 that together harbor all the serine and threonine phosphorylation sites and show that three serines (s1356, s1360, and s1364), previously implicated in hd regulation, prevent the interaction of beta4 with the plectin actin-binding domain when phosphorylated
SIGNOR-156873
P19544
Q05066
1
binding
up-regulates
0.2
Here we report that wt1 binds to and acts synergistically with sry to activate transcription from a promoter containing sry-binding sites
SIGNOR-100345
P62714
P32519
1
dephosphorylation
down-regulates activity
0.2
Elf-1 enhances the expression of CD3zeta, whereas it suppresses the expression of FcRgamma gene and lupus T cells have decreased amounts of DNA-binding 98 kDa form of Elf-1. We show that the aberrantly increased PP2A in lupus T cells dephosphorylates Elf-1 at Thr-231. Dephosphorylation results in limited expression and binding of the 98 kDa Elf-1 form to the CD3zeta and FcRgamma promoters. Suppression of the expression of the PP2A leads to increased expression of CD3zeta and decreased expression of FcRgamma genes and correction of the early signaling response
SIGNOR-248591
P68400
Q9UPP1
1
phosphorylation
up-regulates activity
0.2
 The CK2 kinase is responsible for PHF8 phosphorylation at Ser854. PHF8 is phosphorylated by CK2, which regulates binding of PHF8 to TopBP1. The Ser854 residue of PHF8 is required for its interaction with TopBP1.
SIGNOR-273628
P43405
Q7Z6Z7
1
phosphorylation
up-regulates activity
0.2
Collectively, these data suggest that TNF induced tyrosine phosphorylation of Mule by Syk contributes to its E3 ligase activity.
SIGNOR-280150
O76064
P0C0S8
1
ubiquitination
up-regulates
0.2
Rnf8 and ubc13 ubiquitylate h2a and h2ax, but other substrates probably exist.
SIGNOR-166174
P05771
O15350
1
phosphorylation
up-regulates activity
0.2
Here, we report that p73 is able to induce cell cycle arrest independently of its amino-terminal transactivation domain, whereas this domain is crucial for p73 proapoptotic functions. its activity is regulated throughout the cell cycle and modified by protein kinase C-dependent phosphorylation at serine residue 388. 
SIGNOR-276234
P21452
P08754
1
binding
up-regulates activity
0.2
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- 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-256879
P0DTC5
Q7Z434
1
binding
down-regulates activity
0.1
Here, we identified SARS-CoV-2 membrane glycoprotein M as a negative regulator of the innate immune response. We found that the M protein interacted with the central adaptor protein MAVS in the innate immune response pathways. This interaction impaired MAVS aggregation and its recruitment of downstream TRAF3, TBK1, and IRF3, leading to attenuation of the innate antiviral response. Our findings reveal a mechanism by which SARS-CoV-2 evades the innate immune response and suggest that the M protein of SARS-CoV-2 is a potential target for the development of SARS-CoV-2 interventions.
SIGNOR-262515
P0C6X7
P17844
1
binding
up-regulates activity
null
To our knowledge, this is the first report to show that SARS-CoV helicase can interact directly with multifunctional protein Ddx5 in cell culture and that inhibition of Ddx5 results in the suppression of viral replication. We speculate that Ddx5 may act as a coactivator by direct binding to the SARS-CoV helicase, resulting in enhanced viral genome transcription and virus proliferation.
SIGNOR-260250
Q02548
P03206
1
binding
down-regulates activity
null
... we demonstrate that Pax5 inhibits Z-mediated lytic viral gene expression and the release of infectious viral particles in latently infected epithelial cell lines. Conversely, we found that shRNA-mediated knockdown of endogenous Pax5 in a Burkitt lymphoma B-cell line leads to viral reactivation. Furthermore, we show that Pax5 reduces Z activation of early lytic viral promoters in reporter gene assays and inhibits Z binding to lytic viral promoters in vivo. We confirm that Pax5 and Z directly interact
SIGNOR-269082
P0DTC9
Q13283
1
binding
down-regulates activity
null
N targets stress granule protein G3BP1, an essential antiviral protein which is known to induce innate immune response through multiple mechanisms
SIGNOR-260749
Q12834
O60566
0
phosphorylation
up-regulates activity
0.993
Furthermore, BUBR1 phosphorylates p55CDC in vitro, and the phosphorylation of p55CDC by BUBR1 appears to be correlated with spindle checkpoint activation.
SIGNOR-279507
Q12834
O43683
0
phosphorylation
down-regulates activity
0.992
Bub1 directly phosphorylates Cdc20 in vitro and inhibits the ubiquitin ligase activity of APC/C(Cdc20) catalytically. A Cdc20 mutant with all six Bub1 phosphorylation sites removed is refractory to Bub1-mediated phosphorylation and inhibition in vitro. 
SIGNOR-250606
Q9UHB9
O76094
0
binding
up-regulates activity
0.99
Taken together our data show that binding of the SRP68/72 heterodimer follows an ultrasensitive response dependent on the SRP72 C-terminus. Although the large solenoids of SRP68/72 have not been structurally characterized due to intrinsic flexibility, they serve as important contact sites in ribosome interaction.
SIGNOR-261164
Q8N122
P42345
0
phosphorylation
up-regulates activity
0.989
The phosphorylation of raptor is stimulated by insulin and inhibited by rapamycin. Importantly, the site-directed mutation of raptor at one phosphorylation site, Ser(863), reduced mTORC1 activity both in vitro and in vivo.
SIGNOR-184959
Q92900
Q9HAU5
0
binding
up-regulates activity
0.979
UPF2 and UPF3b increase UPF1 ATPase activity
SIGNOR-265246
Q12834
P53350
0
phosphorylation
down-regulates quantity by destabilization
0.977
Plk1 directly bound to Cdc20 and phosphorylates it on serine-170 located in CRY-box. Whereas wild-type Cdc20 was degraded according to progress cell cycle beyond mitosis, the phosphorylation-defective mutant, which serine-170 was changed into alanine, was not destroyed in early G1 phase. 
SIGNOR-276493
P20248
P24941
0
phosphorylation
up-regulates
0.977
Here we present evidence from in vitro and in vivo assay systems that the degradation of human cyclin a can be inhibited by kinase-inactive mutants of cdk2 and cdc2cdk2 can phosphorylate cyclin a on ser-154
SIGNOR-74466
Q9H211
O75496
0
binding
down-regulates activity
0.972
Here we show that geminin interacts tightly with Cdt1, a recently identified replication initiation factor necessary for MCM loading.
SIGNOR-261680
Q92900
Q96Q15
0
phosphorylation
up-regulates
0.971
Smg-1 directly phosphorylates upf1 helicase, another key component of nmd, upon recognition of ptc on postspliced mrna during the initial round of translation. Phosphorylated-upf1 recruits the smg-5/smg-7 complex to induce ribosome dissociation and decapping-mediated decay. T28 and s1096 are responsible for phospho-specific recruitment of smg-6 to the n-terminal conserved region, and the smg-5/smg-7 heterodimer complex to the c-terminal sq-rich region of upf1, respectively
SIGNOR-200785
P04637
Q00987
0
ubiquitination
down-regulates quantity by destabilization
0.968
The E3 ubiquitin ligase, MDM2, uses a dual-site mechanism to ubiquitinate and degrade the tumor suppressor protein p53, involving interactions with the N-terminal hydrophobic pocket and the acidic domain of MDM2.
SIGNOR-196116
P14635
Q12834
0
binding
down-regulates quantity by destabilization
0.968
These results suggested that cyclin A is a target of the Cdc20-associated APC/C in human cells.
SIGNOR-272578
P62993
P29353
0
binding
up-regulates
0.965
TGF-beta-induced ShcA phosphorylation induces ShcA association with Grb2 and Sos, thereby initiating the well-characterised pathway linking receptor tyrosine kinases with Erk MAP kinases.
SIGNOR-236366
P49768
Q92542
0
binding
up-regulates
0.965
Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2.
SIGNOR-118852
Q9ULW0
O14965
0
phosphorylation
up-regulates activity
0.965
Here we show that TPX2, a microtubule-bundling protein and activator of Aurora A, plays an important role. TPX2 was phosphorylated by Aurora A during mitosis. Its phospho-null mutant caused short metaphase spindles coupled with low microtubule flux rate. Interestingly, phosphorylation of TPX2 regulated its interaction with CLASP1 but not Kif2a.|This suggests that TPX2 phosphorylation positively regulates the function of CLASP1.| This is in accord with a phosphoproteomics study that identified S121 and S125 as potential phosphorylation sites for Aurora A in mitotic HeLa cells
SIGNOR-265089
Q9HBI1
Q13418
0
phosphorylation
up-regulates activity
0.965
These results indicate that affixin directly associates with \u03b1-actinin only when its CH2 domain is phosphorylated by ILK.|This may indicate that phosphorylation of the CH2 domain by ILK induces a conformational change of the CH2 domain of affixin, which enables affixin to interact with alpha-actinin to evoke the subsequent maturation of the FA complex.
SIGNOR-278259
O60216
Q8N3U4
0
binding
up-regulates quantity by stabilization
0.965
Cohesin is an evolutionarily conserved complex composed of four core proteins (SMC1A, SMC3, RAD21 and either STAG2 or STAG1) that form a ring-shaped structure able to encircle chromatin
SIGNOR-261511
P11802
P24385
0
binding
up-regulates
0.964
D-type cyclins (cyclin d1, d2, or d3) and their associated cyclin-dependent kinases (cdk4, cdk6) connect signals from cytokines to the cell cycle machinery, and they propel cells through the g1 restriction point and into the s phase when activated by cyclin d1, cdk4 is able to phosphorylate prb,
SIGNOR-201666
P49736
O00311
0
phosphorylation
up-regulates
0.962
In this work, by in vitro kinase reactions and mass spectrometry analysis of the products, we have mapped phosphorylation sites in the n terminus of mcm2 by cdc7, cdk2, cdk1, and ck2
SIGNOR-143984
P61011
P09132
0
binding
up-regulates activity
0.962
Mammalian SRP comprises the highly base-paired SRP RNA (also referred to as 7SL RNA) of ∼300 nt and six proteins (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) (Figure ​(Figure1A).1A). The hierarchy of protein addition always starts with the scaffolding protein SRP19 (together with SRP9/14 for the entire SRP) followed by SRP68/72 and finally by SRP54.
SIGNOR-261168
P35269
P13984
0
binding
up-regulates activity
0.962
Direct Interaction Between the Subunit RAP30 of Transcription Factor IIF (TFIIF) and RNA Polymerase Subunit 5, Which Contributes to the Association Between TFIIF and RNA Polymerase II. we showed that RPB5 binds RAP30 but not RAP74 and associates to TFIIF through the binding to RAP30.
SIGNOR-261180
Q9NZ42
Q96BI3
0
binding
up-regulates
0.962
Furthermore, overexpression of aph-1 facilitates pen-2-mediated ps1 proteolysis, resulting in a significant increase in ps1 fragments. Our data reveal a direct role of pen-2 in proteolytic cleavage of ps1 and a regulatory function of aph-1, in coordination with pen-2, in the biogenesis of the ps1 complex.
SIGNOR-97104
Q99442
Q9UGP8
0
binding
up-regulates activity
0.96
Sec63 was identified as a novel substrate and binding partner of protein kinase CK2. We identified serine 574, serine 576 and serine 748 as CK2 phosphorylation sites. Phosphorylation of Sec63 by CK2 enhanced its binding to Sec62.
SIGNOR-265273
Q13257
O43683
0
relocalization
up-regulates activity
0.96
Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity
SIGNOR-252018
P35222
P12830
0
binding
up-regulates activity
0.96
At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin
SIGNOR-265863
P49450
Q8NCD3
0
binding
up-regulates activity
0.96
Here we demonstrate that prenucleosomal CENP-A is complexed with histone H4, nucleophosmin 1, and HJURP. Recruitment of new CENP-A into nucleosomes at replicated centromeres is dependent on HJURP. Recognition by HJURP is mediated through the centromere targeting domain (CATD) of CENP-A, a region that we demonstrated previously to induce a unique conformational rigidity to both the subnucleosomal CENP-A heterotetramer and the corresponding assembled nucleosome. We propose HJURP to be a cell-cycle-regulated CENP-A-specific histone chaperone required for centromeric chromatin assembly.
SIGNOR-263707
P49768
Q9NZ42
0
cleavage
up-regulates
0.959
Our data reveal a direct role of pen-2 in proteolytic cleavage of ps1 and a regulatory function of aph-1, in coordination with pen-2, in the biogenesis of the ps1 complex.
SIGNOR-97113
O75143
Q9BSB4
0
binding
up-regulates
0.959
Furthermore, atg101 is important for the stability and basal phosphorylation of atg13 and ulk1
SIGNOR-186989
P67775
P30153
0
binding
up-regulates
0.959
Pr65/a acts as a scaffold protein for binding pp2ac and regulatory b subunits in a heterotrimeric holoenzyme
SIGNOR-138883
Q13616
P63208
0
binding
up-regulates
0.959
The human f box protein beta-trcp associates with the cul1/skp1 complex and regulates the stability of beta-catenin.
SIGNOR-64511
P34998
P06850
0
binding
up-regulates
0.958
Crf and ucn bind and activate crf-r1 with similarly high affinities.
SIGNOR-108713
P33991
O00311
0
phosphorylation
up-regulates
0.958
Activation of the eukaryotic replicative dna helicase, the mcm2-7 complex, requires phosphorylation by cdc7/dbf4 (dbf4-dependent kinase or ddk), which, in turn, depends on prior phosphorylation of mcm2-7 by an unknown kinase (or kinases).we propose that the resulting mec1 modification of mcm4 and mcm6 further activates ddk phosphorylation of mcm2-7 ( fig. 7aii ).
SIGNOR-169453
Q92900
Q9BZI7
0
binding
up-regulates activity
0.957
UPF2 and UPF3b increase UPF1 ATPase activity
SIGNOR-265247
P42768
P60953
0
binding
up-regulates activity
0.957
Cdc42 can induce Arp2/3-mediated filopodia formation through the activation of WASp (Wiskott-Aldrich syndrome proteins) and neuronal N-WASp (Rohatgi et al., 1999). Similarly, Rac1-enhanced lamellipodia formation is related to Arp2/3 activation by the WAVE (WASP-family verprolin-homologous) complex
SIGNOR-261869
Q07817
O43521
0
binding
down-regulates activity
0.956
Bim can induce apoptosis by interacting with anti-apoptotic members of the bcl2 family, including bcl2, bcl-xl and mcl-1.Bim binds bcl-2, bcl2l1, bcl2l2, mcl1 and a1 tightly.
SIGNOR-178679
P08069
P05019
0
binding
up-regulates activity
0.956
Binding of IGF1 to its receptor leads to activation of its intrinsic tyrosine kinase and autophosphorylation, thus generating docking sites for insulin receptor substrate (IRS), which is also phosphorylated by the IGF1 receptor.
SIGNOR-175662
P19447
P18074
0
binding
up-regulates
0.955
Xpd helps xpb in promoter opening and as such participates in the transcription reaction.
SIGNOR-64672
P04629
P01138
0
binding
up-regulates
0.955
Ngf is the preferred ligand for trka, bdnf and nt4/5 are preferred for trkb, and nt3 for trkc (barbacid 1994). These specificities are not absolute, and nt3 is also a ligand for trka and trkb.
SIGNOR-85114
O60341
Q9UKL0
0
binding
up-regulates activity
0.955
CoREST protects LSD1 from proteasomal degradation and also plays an indispensable role in LSD1-mediated demethylation of nucleosomal substrates in vitro. in contrast to CoREST, which is a positive regulator of LSD1 activity, the in vitro evidence presented above suggests that BHC80 may function to inhibit LSD1 activity.
SIGNOR-264506
P55211
O14727
0
binding
up-regulates activity
0.954
Caspase-9 and Apaf-1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome c and dATP, an event that leads to caspase-9 activation.
SIGNOR-53576
P40855
P56589
0
binding
up-regulates activity
0.954
PEX3 is required for PEX19 to dock at peroxisomes, interacts specifically with the docking domain of PEX19, and is required for recruitment of the PEX19 docking domain to peroxisomes.
SIGNOR-253026
P05412
P01100
0
binding
up-regulates activity
0.953
The cFos proto-oncoprotein associates with cJun to form a heterodimer with increased DNA binding and transcriptional activities.
SIGNOR-252087
Q13480
Q06124
0
dephosphorylation
down-regulates activity
0.952
These results suggest that Tyr(P)-627 and Tyr(P)-659 of Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) that binds and activates SHP2.|Thus, physical association of activated SHP2 with Gab1 is necessary and sufficient to mediate the ERK mitogen-activated protein kinase activation. Phosphopeptides derived from Gab1 were dephosphorylated by active SHP2 in vitro.
SIGNOR-248674
P42345
Q15382
0
binding
up-regulates activity
0.95
Rheb stimulates the phosphorylation of mtor and plays an essential role in regulation of s6k and 4ebp1 in response to nutrients and cellular energy status.
SIGNOR-162006
Q9UHB9
P09132
0
binding
up-regulates activity
0.95
Mammalian SRP comprises the highly base-paired SRP RNA (also referred to as 7SL RNA) of ∼300 nt and six proteins (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) (Figure ​(Figure1A).1A). The hierarchy of protein addition always starts with the scaffolding protein SRP19 (together with SRP9/14 for the entire SRP) followed by SRP68/72 and finally by SRP54.
SIGNOR-261167
Q13618
Q14145
0
binding
up-regulates activity
0.95
Keap1 is a BTB-Kelch protein that functions as a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex. Keap1 targets its substrate, the Nrf2 transcription factor, for ubiquitination and subsequent degradation by the 26 S proteasome.  The N-terminal BTB domain and central linker region of Keap1 bind Cul3, whereas the C-terminal Kelch domain of Keap1 binds Nrf2 via residues located within loops that extend out from the bottom of the Kelch domain
SIGNOR-268925
P60880
P21579
0
binding
up-regulates activity
0.95
Because synaptotagmins bind SNAP-25 and Ca2+, SNAP-25 has also been linked to the Ca2+ dependence of exocytosis (42). One model suggests that synaptotagmin blocks full SNARE fusion pore formation by binding to t-SNAREs.This interaction prevents fusion from occurring in the absence of calcium. When Ca2+ is present, synaptotagmin releases the t-SNAREs so they can fully zipper with the v-SNARE, leading to fusion
SIGNOR-263975
Q92922
P51532
0
binding
up-regulates
0.95
The remodeling activity of brg1 and hbrm is stimulated by baf170/baf155 and is further stimulated when ini1 is added.
SIGNOR-65441
Q06330
P46531
0
binding
up-regulates
0.95
The intracellular part of the notch receptor is cleaved off and translocates to the nucleus, where it binds to the transcription factor rbp-j.
SIGNOR-183510
P08151
Q9UMX1
0
binding
down-regulates activity
0.949
Here we characterize structural and functional determinants of Su(fu) required for Gli regulation and show that Su(fu) contains at least two distinct domains: a highly conserved carboxy-terminal region required for binding to the amino-terminal ends of the Gli proteins and a unique amino-terminal domain that binds the carboxy-terminal tail of Gli1. While each domain is capable of binding to different Gli1 regions independently, interactions between Su(fu) and Gli1 at both sites are required for cytoplasmic tethering and repression of Gli1
SIGNOR-249591
P00533
P01133
0
binding
up-regulates activity
0.949
Epidermal growth factor (egf) regulates cell proliferation and differentiation by binding to the egf receptor (egfr) extracellular region, comprising domains i-iv, with the resultant dimerization of the receptor tyrosine kinase.
SIGNOR-186159
P00734
P01008
0
cleavage
down-regulates activity
0.948
Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1
SIGNOR-264136
P04637
O15151
0
ubiquitination
down-regulates quantity by destabilization
0.948
Here we demonstrate that MdmX acts as a ubiquitin ligase in vitro, being capable of autoubiquitination, as well as mediating the ubiquitination of p53. 
SIGNOR-271389
Q06609
P51587
0
binding
up-regulates activity
0.947
We suggest that interactions of the BRCA2 C-terminal region with RAD51 may facilitate efficient nucleation of RAD51 multimers on DNA and thereby stimulate recombination-mediated repair.
SIGNOR-259905
P18074
P28715
0
binding
up-regulates quantity by stabilization
0.947
The NER protein XPG was also found to associate with the TFIIH complex by interacting directly with XPD stabilizing the interaction between TFIIH and the CAK-XPD complex
SIGNOR-251974
P12830
O60716
0
binding
up-regulates quantity by stabilization
0.947
P120 regulates E-cadherin turnover at the cell membrane. Because direct binding of p120 to E-cadherin is required, it is possible that p120 binding blocks the interaction of an unknown binding partner (or event) that targets E-cadherin for degradation
SIGNOR-252123
P49768
Q96BI3
0
binding
up-regulates
0.947
By using co-immunoprecipitation and nickel affinity pull-down approaches, we now show that mammalian aph-1 (maph-1), a conserved multipass membrane protein, physically associates with nicastrin and the heterodimers of the presenilin amino- and carboxyl-terminal fragments in human cell lines and in rat brain.
SIGNOR-93262
Q8TAT6
P55072
0
binding
up-regulates activity
0.946
These findings ascribe specific functions to each of the components of the VCP-UFD1L-NPL4 complex in Vpu-mediated CD4 degradation: VCP energizes the process through ATP binding and hydrolysis, UFD1L binds ubiquitinated CD4 through recognition of K48 Ub chains, and NPL4 stabilizes UFD1L. VCP is thus likely to provide the energy required for extraction of CD4 from membranes.
SIGNOR-252423
P24530
P05305
0
binding
up-regulates
0.946
Endothelin-1 (et-1) and angiotensin ii (angii), two potent vasoactive peptides involved in the regulation of cardiovascular homeostasis, also induce mitogenic and pro-angiogenic responses in vitro and in vivo. Both peptides are produced by cleavage of inactive precursors by metalloproteases (endothelin-converting enzyme and angiotensin-converting enzyme, respectively) and activate two subtypes of membrane receptors (eta-r and etb-r for et-1, at1r and at2r for angii) that all belong to the superfamily of g-protein coupled receptors.
SIGNOR-145762
Q9NWZ3
Q99836
0
binding
up-regulates activity
0.946
Signaling between MyD88 and TRAF6 is mediated by members of the IL-1R-associated kinase (IRAK) family; however, the exact function of each IRAK protein remains controversial. IRAK-1 is required for the optimal transduction of IL-1R- and TLR-mediated signals, but IRAK-1 can be replaced by other IRAKs. Surprisingly, gene targeting studies show that the newest IRAK protein, IRAK-4, has an essential role in mediating signals initiated by IL-1R and TLR engagement.
SIGNOR-252097
O94782
Q8TAF3
0
binding
up-regulates activity
0.946
In vitro reconstitution of USP1 deubiquitinating enzyme activity, using either ubiquitin-7-amido-4-methylcoumarin (Ub-AMC) or purified monoubiquitinated FANCD2 protein as substrates, demonstrates that UAF1 functions as an activator of USP1. UAF1 binding increases the catalytic turnover (kcat) but does not increase the affinity of the USP1 enzyme for the substrate (KM).
SIGNOR-263274
Q12834
P51955
0
phosphorylation
up-regulates activity
0.945
In summary, we have demonstrated that Nek2 can associate with and phosphorylate Mad2 and Cdc20.|The results presented here support a model in which Nek2 modulates the functions of Mad2 and Cdc20 in the mitotic checkpoint and elevation of Nek2 levels may contribute to chromosome instability by interfering with the control of the checkpoint.
SIGNOR-278366
Q99836
P14778
0
binding
up-regulates activity
0.945
Interleukin-1 (il-1) stimulates the association of the il-1 receptor-associated protein kinase (irak) with the heterodimer of il-iri and il-iracp via the adapter protein myd88.
SIGNOR-67140
Q14674
O95997
0
binding
down-regulates activity
0.945
Prior to anaphase, separase is kept inactive by its inhibitor securin
SIGNOR-275538