IdA
stringlengths
6
21
IdB
stringlengths
6
21
labels
float64
0
2
mechanism
stringclasses
40 values
effect
stringclasses
10 values
score
float64
0.1
0.99
sentence
stringlengths
10
1.63k
signor_id
stringlengths
12
14
Q00534
P42771
0
binding
down-regulates
0.871
In addition, cytoplasmic p16 bound cyclin dependent kinase (cdk)4/6, potentially indicating that p16 could have a function in the cytoplasm.
SIGNOR-140412
P08559
Q15120
0
phosphorylation
down-regulates activity
0.871
Activity of the mammalian pyruvate dehydrogenase complex is regulated by phosphorylation-dephosphorylation of the alpha subunit of the pyruvate dehydrogenase (e1) component. Phosphorylation is carried out by four pyruvate dehydrogenase kinase (pdk) isoenzymes.
SIGNOR-109647
P32239
P06307
0
binding
up-regulates
0.871
Cck8 interacts with nanomolar affinities with two different receptors designated cck-a and cck-b
SIGNOR-66339
P04637
P24941
0
phosphorylation
up-regulates activity
0.871
The N-terminus of E2F1 can interact directly with a region towards the C-terminus of p53, resulting in increased nuclear retention of p53 and p53-mediated transcription and apoptosis. This is inhibited by competition between p53 and cyclin A at the binding site within E2F19,10. The interaction between p53 and E2F1 is enhanced by phosphorylation of p53 on Ser315, a residue within the E2F1 binding region that is phosphorylated by cell cycle kinases such as cdk1, cdk2, cdk9 and Aurora kinase A
SIGNOR-119379
P11802
P42773
0
binding
down-regulates
0.871
The first group, including p16ink4a, p15ink4b,p18ink4cand p19ink4d, is specific for the g1 cdks,cdk4and cdk6, inhibiting the kinase activity of cyclin d/cdk4-cdk6 complexes on prb.
SIGNOR-44598
Q8IZL2
Q06330
0
binding
up-regulates
0.871
When bound to the active intracellular domain of notch (nicd), rbpj recruits a coactivator complex, including a mastermind homologue (maml1-3 in mammals), and drives a complex transcriptional program with pervasive phenotypic effects
SIGNOR-176197
P04049
P01111
0
relocalization
up-regulates
0.87
The raf family of proteins (raf-1, a-raf, and b-raf) bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases.
SIGNOR-175231
Q12778
P31749
0
phosphorylation
down-regulates activity
0.87
Here we show that the activation of phosphatidylinositol 3 (PI3) kinase by extracellular growth factors induces phosphorylation, nuclear export, and transcriptional inactivation of FKHR1, a member of the FKHR subclass of the forkhead family of transcription factors. Protein kinase B (PKB)/Akt, a key mediator of PI3 kinase signal transduction, phosphorylated recombinant FKHR1 in vitro at threonine-24 and serine-253. Mutants FKHR1(T24A), FKHR1(S253A), and FKHR1(T24A/S253A) were resistant to both PKB/Akt-mediated phosphorylation and PI3 kinase-stimulated nuclear export.
SIGNOR-236163
Q12933
Q15628
0
binding
up-regulates activity
0.87
The high affinity of the tradd-traf2 interaction is required for efficient suppression of apoptosis upon stimulation of the tumor necrosis factor receptor1 (tnfr1), tnf-receptor-associated death domain (tradd) provides a scaffold for the assembly of complex i at the plasma membrane by binding receptor interacting protein 1 (rip1), tnfreceptor- associated factor 2 ,traf2 these results provide evidence that tradd can serve as an adaptor protein and recruit traf1, traf2, or both to tnfrsf1a. The demonstration that tradd interacts with traf2 and fadd, and can recruit both to tnfrsf1a, suggested that traf2 and fadd may be involved in tnfrsf1a tradd-mediated signaling. That these interactions define two distinct signaling pathways emanating from tradd (figure 9) is supported by the ability of traf2 and fadd to activate nf-kb and induce apoptosis, respectively.
SIGNOR-179446
Q15561
Q9GZV5
0
binding
up-regulates
0.869
When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead14.
SIGNOR-201459
O15055
P48730
0
phosphorylation
down-regulates quantity by destabilization
0.869
Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2. We have now extended our previous studies to show that human casein kinase Idelta (hCKIdelta), the closest homologue to hCKIepsilon, associates with and phosphorylates hPER1 and causes protein instability. Furthermore, we observed that both hCKIdelta and hCKIepsilon phosphorylated and caused protein instability of human period 2 protein (hPER2).
SIGNOR-268000
P40189
P05231
0
binding
up-regulates activity
0.869
A crystal structure of the ligand-binding domains of gp130 in complex with human interleukin-6 (il-6) and its a-receptor (il-6ralpha) revealed a hexameric architecture in which the gp130 membrane-distal regions were approximately 100 a apart, in contrast to the close apposition seen between short cytokine receptor complexes.
SIGNOR-48041
P05198
Q9UI10
0
guanine nucleotide exchange factor
up-regulates activity
0.869
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-269127
P14784
P60568
0
binding
up-regulates
0.869
Il-2 is a cytokine that functions as a growth factor and central regulator in the immune system and mediates its effects through ligand-induced hetero-trimerization of the receptor subunits il-2r alpha, il-2r beta, and gamma(c).
SIGNOR-144540
P35568
P08069
0
phosphorylation
up-regulates
0.868
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-175665
Q13261
P40933
0
binding
up-regulates
0.868
Interleukin-15 specificity and high affinity binding are conferred by the IL-5-specific but nonsignaling IL-15R alpha subunit, which is structurally similar (but not homologous) to the alpha receptor subunit of IL-2
SIGNOR-157415
P28347
Q9GZV5
0
binding
up-regulates
0.868
When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead1?_?_?4.
SIGNOR-192768
Q9NPH3
P01584
0
binding
up-regulates
0.867
The recently described il-1r accessory protein (il-1r acp) interacts with il-1beta and the il-1 type-ir (il-1ri).
SIGNOR-61744
Q9NRM7
Q9H8S9
0
binding
up-regulates
0.867
Lats1/2 are activated by association with the highly homologous scaffold proteins mps one binder kinase activator-like 1a (mobkl1a) and 1b (mobkl1b), which are collectively referred to as mob1
SIGNOR-169755
P17181
P01574
0
binding
up-regulates
0.867
Ifn-alpha, ifn-beta, and ifn-omega, induce somewhat different cellular effects but act through a common receptor complex, ifnar, composed of subunits ifnar-1 and ifnar-2.
SIGNOR-104663
Q8WU20
P11362
0
phosphorylation
up-regulates activity
0.867
As shown in xref , wild type FGFR1c phosphorylated FRS2\u03b1 on tyrosine 196 whereas the V429E mutant did not.
SIGNOR-280013
P60842
P23588
0
binding
up-regulates activity
0.867
Either eIF4B or eIF4H stimulated the initial rate and amplitude of eIF4A-dependent duplex unwinding, and the magnitude of stimulation is dependent on duplex stability
SIGNOR-261293
Q495A1
P15151
0
binding
up-regulates activity
0.867
Poliovirus receptor (PVR/CD155) is a ligand of the paired NK receptors, DNAM-1 (activating) and TIGIT (inhibiting). NK cells can kill cancer cells expressing PVR via the DNAM-1-mediated activating signaling (11,12).
SIGNOR-261425
P16499
P18545
0
binding
down-regulates activity
0.866
Both PDE6C-A and PDE6C-B were potently and similarly inhibited by both Pγ subunits, with Ki values ranging from 33 to 46 pm (Fig. 5). The inhibition analysis revealed no significant differences between PDE6C-A and PDE6C-B
SIGNOR-260010
P42229
O60674
0
phosphorylation
up-regulates activity
0.866
Jak2 kinase induces tyrosine phosphorylation, dimerization, nuclear translocation, and dna binding of a concomitantly expressed stat5 protein
SIGNOR-249507
P31785
P60568
0
binding
up-regulates
0.866
Il-2 is a cytokine that functions as a growth factor and central regulator in the immune system and mediates its effects through ligand-induced hetero-trimerization of the receptor subunits il-2r alpha, il-2r beta, and gamma(c).
SIGNOR-144543
Q9NPB6
P41743
0
phosphorylation
up-regulates quantity by stabilization
0.866
APKC associates and phosphorylates Par6 on S345. aPKC expression stabilizes Par6 protein levels. We show that the aPKC, PKCι, interacts with TGF-β receptors through Par6 and that these proteins localize to the leading edge of migrating cells. Furthermore, Par6 phosphorylation on serine 345 by TGF-β receptors is enhanced in the presence of aPKC. aPKC kinase activity, as well as an association with Par6, were found to be important for Par6 phosphorylation.
SIGNOR-276432
P37173
P10600
0
binding
up-regulates
0.866
T?RII Is known to bind the isoforms tgf??1 And tgf??3. Binding of these ligands causes recruitment of the type i receptor (t?RI) into a signalling receptor complex followed by activation of t?RI Through transphosphorylation
SIGNOR-104798
Q15750
Q9Y4K3
0
binding
up-regulates activity
0.865
The irak1/traf6 complex can also activate jnk and p38 signalling through assembly of a catalytically active tab2-tab3-tak1 complex.
SIGNOR-205455
P51692
O60674
0
phosphorylation
up-regulates
0.865
Jak2 kinase induces tyrosine phosphorylation, dimerization, nuclear translocation, and dna binding of a concomitantly expressed stat5 protein
SIGNOR-56894
P67775
Q13362
0
binding
up-regulates activity
0.864
We have identified by two-hybrid interaction a new human gene family encoding PP2A B subunits. This family, denoted B56, contains three distinct genes, one of which is differentially spliced.
SIGNOR-268155
Q9NYJ8
Q13546
0
binding
up-regulates activity
0.864
TNF_ induced the polyubiquitination of RIP and the association of polyubiquitinated RIP with TAB2.
SIGNOR-128406
P61586
Q07960
0
gtpase-activating protein
down-regulates activity
0.864
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-260458
P0CG48
P09936
0
cleavage
up-regulates quantity
0.864
These data suggest that the physiological role of UCH is to hydrolyze small adducts of ubiquitin and to generate free monomeric ubiquitin from ubiquitin proproteins, but not to deubiquitinate ubiquitin-protein conjugates or disassemble polyubiquitin chains
SIGNOR-249693
P30793
P30047
0
binding
down-regulates activity
0.864
The enzyme activity of GTP cyclohydrolase I is controlled by a regulatory protein for this enzyme, GFRP, which is a pentamer of identical subunits. GFRP mediates feedback inhibition of GTP cyclohydrolase I activity by BH4, and the inhibition by BH4 is reversed by phenylalanine
SIGNOR-252203
P32241
P01282
0
binding
up-regulates
0.864
Pacap binds to a pacap-specific receptor (pac1) and to vpac receptors (vpac1 and vpac2), which share high affinity for vasoactive intestinal polypeptide (vip).
SIGNOR-116122
Q9HCK4
O94813
0
binding
up-regulates activity
0.863
This observation suggests that Slit2 may require the Robo2 and Robo3 receptors in this process . Slit2 causes the miRNA miR-182 to release cofilin1 mRNA, potentiating cofilin1 local translation and resulting in growth cone collapse. The use of morpholinos or RNAi to knockdown robo2 and robo3 in X. laevis RGCs, would be useful to further confirm that Robo2 and Robo3 are the receptors involved in Slit2-dependent cofilin1 translation.
SIGNOR-268380
Q9UQB8
P60953
0
binding
up-regulates activity
0.863
We conclude that the interaction of Cdc42 with the partial CRIB motif of IRSp53 relieves an intramolecular, autoinhibitory interaction with the N terminus, allowing the recruitment of Mena to the IRSp53 SH3 domain. This IRSp53:Mena complex initiates actin filament assembly into filopodia.
SIGNOR-268424
P22694
P10644
0
binding
down-regulates activity
0.863
Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets
SIGNOR-258755
P09884
Q7L590
0
relocalization
up-regulates quantity by stabilization
0.862
Mcm10 is an essential eukaryotic protein required for the initiation and elongation phases of chromosomal replication. Specifically, Mcm10 is required for the association of several replication proteins, including DNA polymerase alpha (pol alpha), with chromatin.
SIGNOR-261271
P51681
P13236
0
binding
up-regulates activity
0.862
The investigators showed that myoblasts constitutively express receptors for CCL2 (CCR2), CCL3 (CCR1 and CCR5), and CCL4 (CCR5), and that stimulation with either CCL2 or CCL4 was sufficient to promote myoblast proliferation. 
SIGNOR-255116
Q13501
P60520
0
binding
up-regulates activity
0.862
P62 binds both to lc3a and -b and the related gabarap family proteins/this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguisha
SIGNOR-156307
Q04206
Q9Y6K9
0
phosphorylation
up-regulates activity
0.862
Chromatographic fractionation of cell extracts allowed the identification of two distinct enzymatic activities phosphorylating ser-536. Peak 1 represents an unknown kinase, whereas peak 2 contained ikkalpha, ikkbeta, ikkepsilon, and tbk1. collectively, our results provide evidence for at least five kinases that converge on ser-536 of p65 and a novel function for this phosphorylation site in the recruitment of components of the basal transcriptional machinery to the interleukin-8 promoter.
SIGNOR-129947
P84077
Q8N6T3
0
gtpase-activating protein
up-regulates activity
0.862
The ARFGAP molecule binds to switch 2 and helix α3 to orient ARF1 residues for catalysis, but it supplies neither arginine nor other amino acid side chains to the GTPase active site.
SIGNOR-261915
O43603
P22466
0
binding
up-regulates
0.862
Galanin showed high affinity for the galr1 (ic(50) = 0.097 nm) and galr2 receptors (ic(50) = 0.48 nm).
SIGNOR-73125
O95166
Q9Y4P1
0
cleavage
up-regulates activity
0.861
In vivo and in vitro biochemical analyses have shown that human atg4b is an authentic cysteine protease essential for cleavage of the c terminus of each atg8 homolog to expose the c-terminal gly
SIGNOR-141929
Q14457
Q9P2Y5
0
binding
up-regulates activity
0.861
UVRAG interacts with Beclin 1, leading to activation of autophagy and thereof inhibition of tumorigenesis.
SIGNOR-150825
P84022
O95405
0
binding
up-regulates activity
0.861
We now identify SARA (for Smad anchor for receptor activation), a FYVE domain protein that interacts directly with Smad2 and Smad3. SARA functions to recruit Smad2 to the TGFbeta receptor by controlling the subcellular localization of Smad2 and by interacting with the TGFbeta receptor complex.
SIGNOR-62874
O43683
P06493
0
phosphorylation
up-regulates
0.861
The plk1-bub1 interaction requires the polo-box domain (pbd) of plk1 and is enhanced by cyclin-dependent kinase 1 (cdk1)-mediated phosphorylation of bub1 at t609
SIGNOR-147065
Q02078
Q09472
0
binding
up-regulates
0.861
Once released from associated repressors, MEF2 is bound by the p300 coactivator, which possesses histone acetyltransferase activity. Thus, the net result of CaMK signaling to MEF2 complexes is increased histone acetylation (Ac), which relaxes chromatin and stimulates MEF2 target gene transcription.
SIGNOR-232165
Q5VWK5
Q9NPF7
0
binding
up-regulates
0.861
We identify a novel member of the hemopoietin receptor family as a subunit of the receptor for il-23, il-23r.
SIGNOR-87805
P08069
P18031
0
dephosphorylation
down-regulates activity
0.861
Ptp-1b can regulate igf-ir kinase activity and function and that loss of ptp-1b can enhance igf-i-mediated cell survival, growth, and motility in transformed cells.
SIGNOR-115709
Q8IZL2
Q99466
0
binding
up-regulates
0.86
We show here identification of two new members of human mam family (human mastermind-2 (hmam-2) and human mastermind-3 (hmam-3)), which retain characteristics similar to human mastermind-1 (hmam-1) and drosophila mastermind. Both hmam-2 and hmam-3 stabilize and participate in the dna-binding complex rbp-j/cbf-1 protein and the notch intracellular domains that serve as intermediates of the signaling. Both hmam-2 and hmam-3 enhanced the activation of transcription from a target promoter by notch signaling. However, we also show evidence that the activation of the target promoter by notch3 and notch4 is more efficiently potentiated by hmam-2 than by hmam-1 or -3.
SIGNOR-94279
P35222
P49841
0
phosphorylation
down-regulates activity
0.86
Wnt regulation of beta-catenin degradation is essential for development and carcinogenesis. beta-catenin degradation is initiated upon amino-terminal serine/threonine phosphorylation, which is believed to be performed by glycogen synthase kinase-3 (GSK-3) in complex with tumor suppressor proteins Axin and adnomatous polyposis coli (APC).
SIGNOR-116528
P25025
P10145
0
binding
up-regulates
0.86
Il-8 activates both the cxcr1 and the cxcr2 on microvascular endothelial cells, using different signal transduction cascades.
SIGNOR-107983
P10275
Q13772
0
binding
up-regulates
0.86
We demonstrated that ara70 and ar physically interact and that ara70 can function as an androgen-dependent coactivator for ar.
SIGNOR-67684
Q14974
P52294
0
binding
up-regulates activity
0.86
Although ORF6 causes a relocalization of KPNA2 from the cytosol to the ER/Golgi membrane, KPNA2 is not directly involved in the translocation of the STAT1:STAT2:IRF9 (ISGF3) complex into the nucleus; rather, KPNA1 interacts with KPNB1 to initiate ISGF3's nuclear localization.
SIGNOR-260273
O96017
Q13535
0
phosphorylation
up-regulates activity
0.86
Atm- and rad3-related also phosphorylates thr68 in addition to thr26 and ser50, which are not phosphorylated to a significant extent by atm in vitro.Substitution of thr68 with ala reduced the extent of phosphorylation and activation of chk2 in response to ir
SIGNOR-81442
P10912
P01241
0
binding
up-regulates
0.859
The hghr only binds primate gh. Arg43 in hghr interacts with asp171 of hgh.
SIGNOR-34129
Q07817
P55957
0
binding
down-regulates activity
0.859
Overexpression of antiapoptotic proteins including Bcl-XL and/or Bcl-2 contributes to tumor initiation, progression, and resistance to therapy by direct interactions with proapoptotic BH3 proteins. Release of BH3 proteins from antiapoptotic proteins kills some cancer cells and sensitizes others to chemotherapy. Binding of Bcl-XL and Bcl-2 to the BH3 proteins Bad, Bid, and the three major isoforms of Bim was measured for fluorescent protein fusions in live cells using fluorescence lifetime imaging microscopy and fluorescence resonance energy transfer.
SIGNOR-209675
P55210
P98170
0
binding
down-regulates quantity by destabilization
0.859
Our crystal structure of the complex between xiap (linker-bir2) and caspase-7 surprisingly revealed that the linker is the major determinant of binding and inhibition for the caspase.
SIGNOR-105732
P19174
P09619
0
phosphorylation
up-regulates
0.859
Tyrosine phosphorylation has been shown to increase the enzymatic activity of plc-? / we show that the human pdgf ?- And ?-Receptors differ quantitatively in their abilities to associate with and phosphorylate plc-? And to stimulate inositol phosphate production.
SIGNOR-28179
O75943
Q13535
0
phosphorylation
up-regulates activity
0.858
Here we demonstrate that atr but not atm phosphorylates the human rad17 (hrad17) checkpoint protein on ser(635) and ser(645) in vitro.The rfc-related checkpoint protein rad17, a phosphorylation substrate of atr, is critical for atr-mediated checkpoint signaling and cell survival.
SIGNOR-111248
O75051
Q14563
0
binding
up-regulates
0.858
Plexins form stable complexes with neuropilin-1 or -2.
SIGNOR-75168
P31785
P05112
0
binding
up-regulates
0.858
The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for il-4, il-7, il-9, and il-15 as well as il-2. Here we show that the gamma(c) is also shared with the il-21r complex
SIGNOR-108861
Q9UBF6
Q13616
0
binding
up-regulates activity
0.857
SAG was found to be the second family member of Rbx (RING box protein) or ROC (Regulator of cullins) or Hrt that is a component of SCF E3 ubiquitin ligase. Indeed, like ROC1/Rbx1/Hrt1, SAG binds to Cul1 and SAG-Cul1 complex has ubiquitin ligase activity to promote poly-ubiquitination of E2/Cdc34. 
SIGNOR-271444
Q00610
O14976
0
phosphorylation
up-regulates activity
0.857
Clathrin heavy chain (CHC) was phosphorylated at T606 by its association partner cyclin G-associated kinase (GAK). This phosphorylation was required for proper cell proliferation and tumor growth of cells implanted into nude mice. 
SIGNOR-275448
P30411
P01042
0
binding
up-regulates activity
0.857
BK binds receptor B2 (B2R) and triggers inflammation, edema, and symptoms of anaphylaxis.
SIGNOR-263554
Q92956
O43557
0
binding
up-regulates
0.857
A member of the tumor necrosis factor (tnf) superfamily, human tnfsf14 (htnfsf14)/hvem-l (herpes virus entry mediator ligand) was isolated as a cellular ligand for hvem/tr2 and human lymphotoxin beta receptor (ltbetar). Tnfsf14 induces apoptosis and suppresses tumor formation
SIGNOR-79328
P15509
P04141
0
binding
up-regulates
0.857
We have determined the nmr structure of a ligand-binding domain of the granulocyte colony-stimulating factor (g-csf) receptor comparisons between the spectra of the 15n-labelled domain with and without g-csf indicate that the major ligand-recognition site is on the fg loop just upstream of the wsxws sequence.
SIGNOR-72458
P25929
P01303
0
binding
up-regulates
0.857
Analogs of npy and pyy have been synthesized that contain a proline residue in position 34 of the molecule, i.e., [leu31, pro34]npy (fuhlendorff et al., 1990) or [pro34]pyy (grandt et al., 1994b), and are much more potent at y1 than y2receptors.
SIGNOR-56522
P30304
O14757
0
phosphorylation
down-regulates
0.857
The signal for ubiquitination after uv and ir exposure is created by phosphorylation of cdc25a mediated by chk1 and chk2, respectively. Chk1 is a major kinase phosphorylating cdc25a (ser76/124) and cdc25c (ser216).
SIGNOR-163134
Q9Y566
O14490
0
relocalization
up-regulates activity
0.857
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-264586
Q06330
Q9UM47
0
binding
up-regulates
0.857
Both notch 1 and notch 3 ics displace the co-repressor smrt from the dna-binding protein rbp-j kappa on the hes promoter. The latter observation suggests that both notch 3 ic and notch 1 ic can access rbp-j kappa in vivo, and that the difference in activation capacity instead stems from structural differences in the two ics when positioned on rbp-j kappa.
SIGNOR-86128
Q16665
Q96KS0
0
hydroxylation
down-regulates quantity by destabilization
0.856
There are three EglN family members in humans and mice (EglN1, EglN2, and EglN3). Their enzymatic activity requires oxygen, ascorbic acid, iron, and α-ketoglutarate (α-KG). Under hypoxic conditions, EglNs lose their activity and fail to hydroxylate HIFα, which leads to HIFα stabilization
SIGNOR-261999
P30307
O96017
0
phosphorylation
down-regulates activity
0.856
Activated chk2 in turn phosphorylates cdc25c at serine-216 contributing to the g2/m checkpoints. Cds1 phosphorylates and inactivates cdc25 in vitro|CDC25C is phosphorylated on Ser 216 throughout interphase, but not in mitosis. This creates a binding site for 14‐3‐3 proteins | It has been suggested that 14‐3‐3 protein binding is responsible for retaining Cdc25C in the cytoplasm during interphase, thereby contributing to the prevention of premature initiation of mitotic events
SIGNOR-102779
P17612
P31321
0
binding
down-regulates activity
0.856
Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets
SIGNOR-258753
P24928
Q9NP77
0
dephosphorylation
up-regulates activity
0.855
Phosphorylation of serine-2 (S2) and serine-5 (S5) of the C-terminal domain (CTD) of RNA polymerase II (RNAP II) is a dynamic process that regulates the transcription cycle and coordinates recruitment of RNA processing factors. The Fcp1 CTD phosphatase catalyzes dephosphorylation of S2-P.| Depletion of Ssu72 impairs transcription in vitro
SIGNOR-248815
P14635
P30304
0
dephosphorylation
up-regulates activity
0.855
Cdc25A dephosphorylates and activates CyclinE\u2013Cdk2, CyclinA\u2013Cdk2 and CyclinB\u2013Cdk1, whereas Cdc25B and Cdc25C primarily target CyclinB\u2013Cdk1  [4,5] .
SIGNOR-277137
P46527
Q00534
0
phosphorylation
up-regulates
0.855
Phosphorylation on ser-10 is the major site of phosphorylation in resting cells, takes place at the g(0)-g1 phase and leads to protein stability.p27(kip1) was phosphorylated by v-cyclin-cdk6 predominantly on ser10, which enhances its cytoplasmic localization.
SIGNOR-140401
Q9NT62
Q9H492
0
binding
up-regulates
0.855
Lc3-i is activated by the same atg7 involved in atg12 conjugation, transferred to atg3, a second e2-like enzyme, and finally conjugated to pe.
SIGNOR-191543
P08238
P31948
0
binding
down-regulates activity
0.855
Hsp90 chaperone cycle is tightly regulated by another group of proteins referred to as ‘co-chaperones'. Their stability does not depend on Hsp90 function but they interact with distinct Hsp90 conformational states, providing directionality to the Hsp90 cycle4. Furthermore, certain co-chaperones, such as HOP and Cdc37p50 inhibit the Hsp90 chaperone cycle, assisting in delivery of distinct sets of client proteins (steroid hormone receptors and kinases, respectively) to the Hsp90 chaperone machine.
SIGNOR-261412
P42229
P52333
0
phosphorylation
up-regulates
0.854
For these assays, coexpression of wt jak3 with stat5a was found to result in tyrosine phosphorylation of stat5a (lane 2) mediated by jak3, since stat5a coexpressed with the kinase-inactive k855a mutant form of jak3 was not tyrosine phosphorylated.
SIGNOR-182817
P15056
P01111
0
binding
up-regulates activity
0.854
The raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases.
SIGNOR-175219
Q13404
P61088
0
binding
up-regulates activity
0.854
Ubc13, the partner of rnf8 and rnf168, usually cooperates with an e2-like protein, uev1 (also known as ube2v1) or mms2 (also known as ube2v2), for the synthesis of lys63-linked polyubiquitin chains.
SIGNOR-166177
P37173
P01137
0
binding
up-regulates activity
0.853
A cdna encoding the tgf-beta type ii receptor protein has been isolated by an expression cloning strategy. The cloned cdna, when transfected into cos cells, leads to overexpression of an approximately 80 kd protein that specifically binds radioiodinated tgf-beta 1. Excess tgf-beta 1 competes for binding of radioiodinated tgf-beta 1 in a dose-dependent manner and is more effective than tgf-beta 2.
SIGNOR-236080
P36897
P62942
0
binding
down-regulates activity
0.853
Blocking fkbp12/type i receptor interaction with fk506 nonfunctional derivatives enhances the ligand activity, indicating that fkbp12 binding is inhibitory to the signaling pathways of the tgf beta family ligands
SIGNOR-236142
P19838
O14920
0
phosphorylation
down-regulates quantity by destabilization
0.853
Ikkbeta phosphorylates p105 resulting in its degradation, which releases tpl2 resulting in activation of the pro-proliferative map kinase- pathway.
SIGNOR-70473
P78552
P35225
0
binding
up-regulates
0.853
It is now known that this alternate receptor is a heterodimer, the type ii il-4 receptor or the il-13 receptor, which is comprised of IL-4R And IL-13R1.
SIGNOR-100750
P31785
P40933
0
binding
up-regulates
0.853
The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for il-4, il-7, il-9, and il-15 as well as il-2. Here we show that the gamma(c) is also shared with the il-21r complex.
SIGNOR-108815
P30556
P01019
0
binding
up-regulates activity
0.852
AT(1) receptor (AngII type-1 receptor), a G-protein-coupled receptor, mediates most of the physiological and pathophysiological actions of AngII, and this receptor is predominantly expressed in cardiovascular cells, such as VSMCs (vascular smooth muscle cells)
SIGNOR-252293
Q16512
P61586
0
binding
up-regulates activity
0.852
PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome.
SIGNOR-275465
P15735
P46020
0
binding
down-regulates activity
0.852
Phk is among the most complex of the protein kinases so far elucidated. It has one catalytic (gamma) subunit and three different regulatory (alpha, beta, and delta) subunits, a molecular mass of 1.3 X 106 daltons, and each holoenzyme molecule is presumed to contain four molecules of each subunit. The three regulatory subunits inhibit the phosphotransferase activity of the gamma subunit.
SIGNOR-267407
P18075
Q13253
0
binding
down-regulates activity
0.852
We report the crystal structure of the antagonist Noggin bound to BMP-7, which shows that Noggin inhibits BMP signalling by blocking the molecular interfaces of the binding epitopes for both type I and type II receptors.
SIGNOR-256484
P54132
Q13535
0
phosphorylation
up-regulates activity
0.852
It is noteworthy that an active BLM seems to be unnecessary to the activation of BRCA1, either after gamma-rays or HU, even though BRCA1 and BLM helicase are activated by ATR in response to stalled replication, and despite the fact that they colocalize after replication arrest.|These results show that BLM phosphorylation by ATR after replication fork arrest is not important for its relocalization.
SIGNOR-278978
Q7L9L4
Q13043
0
phosphorylation
up-regulates
0.851
Mob1, which forms a complex with lats1/2, is also phosphorylated by mst1/2, resulting in an enhanced lats1/2mob1 interaction.
SIGNOR-175841
P13807
Q9UQK1
0
binding
up-regulates
0.851
In the liver, PTG and PPP1R3B(GL)are expressed at roughly equivalent levels [55], and they jointly promote hepatic glycogen mobilization and storage. PTG overexpression significantly increased glycogen content, mainly due to its ability to promote the redistribution of PP1 and glycogen synthase to glycogen granules, significantly increasing GS activity and glycogen synthesis (Figure 2)
SIGNOR-271733
O14936
Q02410
0
binding
up-regulates activity
0.851
Interaction with Munc18 increases Mint1 binding to CASK.
SIGNOR-264041
P35222
P22223
0
binding
up-regulates activity
0.851
At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin
SIGNOR-265865
P42338
P27986
0
binding
up-regulates activity
0.851
Signal transduction pathways triggered by Tie2 have been extensively examined. Tyr-1101of Tie2 directly associates in a phosphotyrosine (pTyr)-dependent manner with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase, which in turn activate PI 3-kinase, leading to cell motility and survival
SIGNOR-242640