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P04637
O95831
1
transcriptional regulation
up-regulates quantity by expression
0.351
P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway.
SIGNOR-267462
Q15121
O43464
2
binding
down-regulates
0.485
Htra2 promotes cell death by binding and degrading the anti-apoptotic protein pea15
SIGNOR-126966
P01303
P49146
2
binding
up-regulates
0.837
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-56568
P53350
P25490
1
phosphorylation
up-regulates
0.392
More recently, we identified and mapped multiple phosphorylation sites in yy1, including, threonine 39, serine 118, serine 247, threonine 348 and threonine 378. The first kinase proven to phosphorylate yy1 in vivo was plk1, which phosphorylates threonine 39 during g2/m stage of the cell cycle [25]. Ck2_ is another kinase identified as constitutively phosphorylating yy1 at serine 118. This modification protects yy1 cleavage by caspase 7 during apoptosis
SIGNOR-200087
P16885
P38936
1
phosphorylation
up-regulates quantity by stabilization
0.2
Phosphorylation at Ser-146 by PKCδ increases p21 stability
SIGNOR-262963
Q9UBS5
P28482
0
phosphorylation
down-regulates quantity by destabilization
0.2
We found that, in addition to CaMKIIβ, also ERK1/2 is involved in the degradation pathway of GABAB receptors under physiological and ischemic conditions. In contrast to our previous view, CaMKIIβ does not appear to directly phosphorylate S867. Instead, the data support a mechanism in which CaMKIIβ activates ERK1/2, which then phosphorylates S867 and T872 in GABAB1.
SIGNOR-277857
P16112
P08254
0
cleavage
down-regulates quantity by destabilization
0.738
Aggrecan Degradation in Human Cartilage Evidence for both Matrix Metalloproteinase and Aggrecanase Activity in Normal, Osteoarthritic, and Rheumatoid Joints|Stromelysin-1 (MMP-3), as well as other MMPs, cleave aggrecan in the interglobular domain between Asn341 and Phe342 to generate a G1 fragment with the COOH terminus VDIPEN341 (11–13). This fragment has been isolated and identified by NH2-terminal sequence analysis from human OA cartilage (11). A second proteolytic activity identified as “aggrecanase” also cleaves aggrecan in the interglobular domain, but between Glu373 and Ala374 (19–24), generating a G1 fragment with a COOH terminus of NITEGE374
SIGNOR-266986
Q8N2Q7
P58400
2
binding
up-regulates activity
0.84
Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)
SIGNOR-264149
Q8N6P7
Q6X9E4
2
binding
down-regulates quantity by destabilization
0.342
FBXW12 causes depletion of endogenous and plasmid-derived IL-22R in lung epithelia, binds the E3 ligase constituent Skp-1, and facilitates ubiquitination of IL-22R in vitro.
SIGNOR-272426
Q9UKX5
P08047
0
null
up-regulates quantity by expression
0.2
We speculate that the "mesenchymal signature" of alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3, fibroblast-specific combinations of Ets family members and yet unidentified enhancer-binding transcription factors.
SIGNOR-253350
P18031
P35222
1
dephosphorylation
up-regulates activity
0.66
PTP1B modulates the association of beta-catenin with N-cadherin through binding to an adjacent and partially overlapping target site.|The nonreceptor tyrosine phosphatase PTP1B associates with the cytoplasmic domain of N-cadherin and may regulate cadherin function through dephosphorylation of beta-catenin.|Thus, interaction of PTP1B with N-cadherin is essential for its association with beta-catenin, stable expression at the cell surface, and consequently, cadherin function.
SIGNOR-277121
Q9UBY5
P09471
2
binding
up-regulates activity
0.25
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-257141
P15498
P22681
2
binding
up-regulates
0.692
Hese data imply that c-cbl is a molecular adapter that regulates the function of vav
SIGNOR-49188
P54821
O15525
2
binding
down-regulates activity
0.338
Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.
SIGNOR-221961
Q99661
P06493
0
phosphorylation
down-regulates
0.686
We show here that cyclin-dependent kinase 1 (cdk1) phosphorylates t537 in the core domain of mcak and attenuates its microtubule-destabilizing activity in vitro and in vivo. Phosphorylation of mcak by cdk1 promotes the release of mcak from centrosomes and is required for proper spindle formation.
SIGNOR-164761
P43405
P37840
1
phosphorylation
down-regulates
0.532
Here, we show that alpha-synuclein (alpha-syn) is an outstanding substrate for the protein tyrosine kinase p72syk (syk), which phosphorylates three tyrosyl residues in its c-terminal domain (y-125, y-133, and y-136), here, we show that _-syn is an outstanding substrate for syk and that once it is tyrosine phosphorylated, it loses the ability to form oligomers.
SIGNOR-113065
P09471
Q8TDV5
2
binding
up-regulates activity
0.25
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-257241
Q15173
P10415
1
dephosphorylation
down-regulates
0.323
Pp2a directly interacts with the bh4 domain of bcl2 as a docking site to potentially bridge pp2a to bcl2's flexible loop domain containing the target serine 70 phosphorylation site.
SIGNOR-181559
P35568
P06213
0
phosphorylation
up-regulates activity
0.914
All known IRS proteins contain multiple YXXM motifs that upon phosphorylation by activated insulin receptors A previous study using phosphopeptides suggested that tyrosine-phosphorylated YXXM motifs at positions 608 and 939 in rat IRS-1 bind with high affinity to SH2 domains of p85, and motifs at positions 460 and 987 bind with lower affinity (10).
SIGNOR-235975
Q9Y6R4
P52564
1
phosphorylation
up-regulates activity
0.657
When truncated mapkkk4 (deltamapkkk4) was overexpressed in hek293 cells, it was constitutively activeco-expressed map kinase kinase (mkk)-1, mkk-4, mkk-3 and mkk-6 were activated in vivo by deltamapkkk4. All of the above mkks purified from escherichia coli were phosphorylated and activated by deltamapkkk4 immunoprecipitates in vitro.
SIGNOR-62372
Q9NP62
P49841
0
phosphorylation
down-regulates quantity by destabilization
0.2
We demonstrated that GSK-3beta mediates phosphorylation of GCM1 on Ser322, which is recognized by the F-box protein, FBW2, to promote GCM1 ubiquitination and degradation.
SIGNOR-278940
Q7Z570
Q6ZUJ8
1
transcriptional regulation
up-regulates quantity by expression
0.2
ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3).
SIGNOR-269463
Q9UBI6
P17612
2
binding
down-regulates
0.4
As pka suppresses the activity of gli, smo might use the stimulation of pi3k by galfai and gbetagamma subu- nits to block pka in cells that have high levels of camp.
SIGNOR-152615
P06850
P51608
0
transcriptional regulation
down-regulates quantity by repression
0.466
Collectively, these results point to a specific association between WT MeCP2 and the methylated promoter region of Crh in vivo. In contrast, the MeCP2308 protein was not detected at the Crh promoter. | Thus, the results of seqChIP indicate that MeCP2 preferentially associates with a transcriptionally inactive, dimethyl-histone H3 Lys-9-rich form of the Crh promoter in mice.
SIGNOR-264548
O00398
Q14344
2
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-257348
Q01094
P17612
0
phosphorylation
up-regulates activity
0.2
We confirmed the phosphorylation of T130, S235, and S364 by developing monoclonal antibodies against phospho-specific forms of these sites and showed that their phosphorylation is cell cycle-dependent. According to our results, PKA-mediated phosphorylation of E2F1 by PKA inhibits proliferation and glucose uptake and induces caspase-3 activation and senescence.
SIGNOR-277537
Q00535
Q8IWU2
1
phosphorylation
up-regulates
0.497
Here, we demonstrate that lmtk2 is phosphorylated on serine-1418 (lmtk2ser ) by cdk5/p35 and present evidence that this regulates its ability to phosphorylate pp1cthr __
SIGNOR-195329
Q14623
Q9Y6C5
2
binding
down-regulates activity
0.791
Biochemical analysis of ptch and ptch2 shows that they both bind to all hedgehog family members with similar affinity and that they can form a complex with smo.Current models suggest that binding of Shh to PTCH prevents the normal inhibition of the seven-transmembrane-protein Smoothened (SMO) by PTCH.
SIGNOR-61314
O15527
O14529
2
binding
up-regulates activity
0.2
CUX2 Interacts Directly with OGG1 and Stimulate Its Binding to DNA Containing 8-OxoG
SIGNOR-263960
P11309
Q01196
1
phosphorylation
up-regulates activity
0.269
Furthermore, catalytically active Pim-1 kinase was able to phosphorylate Runx1 and Runx3 proteins and enhance the transactivation activity of Runx1 in a dose-dependent fashion.|Pim-1 potentiates transcriptional activity of the RUNX1 transcription factor.
SIGNOR-278976
Q9H2S1
P17612
0
phosphorylation
down-regulates
0.2
Mutagenesis and mass spectrometry studies identified four pka phosphorylation sites: ser465 (minor site) and three amino acid residues ser568, ser569, and ser570 (major sites) within the carboxyl-terminal region. pka activation decreased sk2 surface localization
SIGNOR-145040
Q96J87
P38936
1
post transcriptional regulation
up-regulates quantity by stabilization
0.2
CELF6 binds to the 3'UTR of p21 transcript and increases its mRNA stability. Depletion of CELF6 promotes cell cycle progression, cell proliferation and colony formation whereas overexpression of CELF6 induces G1 phase arrest.
SIGNOR-269044
Q9UHD2
Q7Z434
2
binding
up-regulates activity
0.913
After ligand binding, cGAS and RIG-I signal through respective adaptor proteins STING and MAVS to recruit the kinases IKK and TBK1, which then activate the transcription factors NF-κB and interferon regulatory factor 3 (IRF3), respectively.
SIGNOR-260145
Q8NFZ4
P78352
1
relocalization
up-regulates activity
0.759
Like NRXNs, NLGNs bind to intracellular PDZ-domain proteins, but in contrast to NRXNs, NLGNs bind to class I PDZ domains such as those contained in PSD95, a postsynaptic MAGUK protein65. PSD95 and its homologues are centrally involved in recruiting glutamate receptors at postsynaptic sites66. Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b). A possible role of these interactions is to recruit postsynaptic adaptor proteins to the site of synaptic junctions.
SIGNOR-264193
P04150
P0DMV8
2
binding
down-regulates
0.633
Interestingly, FKBP51 forms complexes in mitochondria with the glucocorticoid receptor and the Hsp90/Hsp70-based chaperone heterocomplex
SIGNOR-251668
O43541
Q99717
0
transcriptional regulation
up-regulates quantity
0.599
Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation
SIGNOR-268940
P67775
P28749
1
dephosphorylation
up-regulates
0.623
Pocket protein family consists of the retinoblastoma tumor suppressor protein (prb) and the functionally and structurally related proteins p107 and p130./dephosphorylation of p130 and p107 in cell extracts is inhibited by concentrations of okadaic acid known to inhibit pp2a, but not pp1. Finally, the pp2a catalytic subunit pp2a/c) specifically interacts with both p130 and p107 / the cell cycle repressor activity of pocket proteins is inactivated by cdk mediated phosphorylation.
SIGNOR-129749
Q93077
Q14493
0
translation regulation
up-regulates quantity by expression
0.2
Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.
SIGNOR-265400
P62136
P04150
1
dephosphorylation
up-regulates activity
0.291
The current study assessed whether PP1\u03b1 can stimulate GR function and tested two different hypotheses: First, that PP1\u03b1 regulates GR activity through suppression of MDM2 activity by dephosphorylating it at Ser166, thereby reducing the MDM2-mediated ubiquitination of GR and the subsequent proteasomal degradation of the receptor, as shown for the MR and AR ( xref ; xref ); and second, that PP1\u03b1 directly dephosphorylates the GR at a particular site to relieve functional repression as demonstrated for PP2A and PP5 ( xref ; xref ; xref ).|The involvement of GR-Ser211 phosphorylation supports the assumption that altered subcellular trafficking is a mechanism less likely contributing to the PP1\u03b1-dependent GR activation.
SIGNOR-277161
Q16695
Q9UGL1
0
demethylation
up-regulates activity
0.2
KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.
SIGNOR-264303
P09630
P09429
2
binding
up-regulates activity
0.298
We show that HMG1 interacts with proteins encoded by the HOX gene family by establishing protein-protein contacts between the HMG box domains and the HOX homeodomain. The functional role of these interactions was studied using the transcriptional activity of the human HOXD9 protein as a model. HMG1 enhances, in a dose-dependent fashion, the sequence-specific DNA binding activity in vitro, and the transcriptional activation in a co-transfection assay in vivo, of the HOXD9 protein.
SIGNOR-219937
O75807
O15105
2
binding
up-regulates
0.679
We found smad7 interacts with growth arrest and dna damage protein, gadd34, a regulatory subunit of the protein phosphatase 1 (pp1) holoenzyme, which subsequently recruits catalytic subunit of pp1 (pp1c) to dephosphorylate t?RI.
SIGNOR-121280
P15531
Q8IVT5
1
phosphorylation
down-regulates
0.543
Autophosphorylated recombinant nm23-h1 phosphorylated ksr in vitro. Using site-directed mutagenesis, we found that nm23-h1 phosphorylated ksr serine 392, a 14-3-3-binding site, consistent with the recent identification of c-tak1 as a kinase for this site.
SIGNOR-90390
Q13085
Q8NHY2
0
ubiquitination
down-regulates quantity by destabilization
0.2
TRB3 appears to inhibit ACC activity by functioning as an adaptor for COP1.  Taken together, these results suggest that TRB3 may promote loss of fat by mediating the COP1-dependent ubiquitination and inactivation of ACC. Taking these results together, we propose that TRB3 may protect against diet-induced obesity by stimulating fatty acid oxidation in adipose during fasting through the COP1-mediated ubiquitination and degradation of ACC (Fig. 4D).
SIGNOR-271598
P04150
P17676
2
binding
up-regulates activity
0.46
The differentiation of 3T3-L1 preadipocytes is regulated in part by a cascade of transcriptional events involving activation of the CCAAT/enhancer-binding proteins (C/EBPs) and peroxisome proliferator-activated receptor gamma (PPARgamma) by dexamethasone (DEX), 3-isobutyl-1-methylxanthine (MIX), and insulin
SIGNOR-250566
Q14703
P36956
1
cleavage
up-regulates activity
0.561
We present evidence that SKI-1 processes peptides mimicking the cleavage sites of the SKI-1 prosegment, pro-brain-derived neurotrophic factor, and the sterol regulatory element-binding protein SREBP-2
SIGNOR-267497
P08581
P14210
2
binding
up-regulates
0.928
Hgf is the ligand for p190met, the receptor tyrosine kinase encoded by the met proto-oncogene.
SIGNOR-38429
P78536
P12931
0
phosphorylation
up-regulates activity
0.458
These data suggests that Src mediates TACE activation in mechanically stressed cardiomyocytes and this mechanism could be exploited for specific blockade of TNFalpha secretion and its detrimental effects in congestive heart failure.|We found that the non receptor tyrosine kinase Src mediates TACE activation in mechanically stretched rat cardiomyocytes by phosphorylating the Tyr 702 residue within the intracellular tail of TACE.
SIGNOR-279115
Q14289
Q9UHD2
1
phosphorylation
up-regulates activity
0.266
 Mechanistically, we demonstrate that PTK2B directly phosphorylates residue Tyr591 of TBK1, which increases TBK1 oligomerization and activation.
SIGNOR-277910
O43613
P50148
2
binding
up-regulates activity
0.466
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-257220
P03206
Q02548
2
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
Q13322
P08069
2
binding
down-regulates
0.739
Grb10 negatively regulates growth factor signaling. It binds the insulinand insulin-like growth factor 1 (igf-1) receptors, and mice without grb10 are larger and exhibit enhanced insulin sensitivity
SIGNOR-174062
P18848
P51812
0
phosphorylation
up-regulates
0.633
Here, we show that rsk2 is required for osteoblast differentiation and function. We identify the transcription factor atf4 as a critical substrate of rsk2 that is required for the timely onset of osteoblast differentiation, for terminal differentiation of osteoblasts, and for osteoblast-specific gene expression
SIGNOR-124436
Q8WZ75
O94813
2
binding
up-regulates
0.634
We show that robo4 binds slit and inhibits cellular migration in a heterologous expression system, analogous to the role of known robo receptors in the nervous system.
SIGNOR-86380
Q9GZV5
O95835
0
phosphorylation
down-regulates
0.791
In response to high cell densities, activated LATS1/2 phosphorylates the WW-domain containing transcriptional co-activators YAP at Ser127 and TAZ at Ser89, promoting 14-3-3 binding and thereby inhibiting their translocation into the nucleus.
SIGNOR-197643
P00403
P0C6X7-PRO_0000037317
2
binding
down-regulates activity
0.2
This result suggests that the nsp10 protein could affect the activities of NADH and cytochrome oxidase II via a direct interaction while being involved in viral replication.
SIGNOR-260254
P04083
P25090
2
binding
up-regulates activity
0.643
We show that the mimetic N-terminal annexin 1 peptide Ac1-25 is able to activate and desensitize not only FPR but also FPRL1 and FPRL2.
SIGNOR-259437
Q06609
Q96B01
2
binding
up-regulates activity
0.771
Homologous recombination (HR) repairs chromosome damage and is indispensable for tumor suppression in humans. RAD51 mediates the DNA strand-pairing step in HR. RAD51 associated protein 1 (RAD51AP1) is a RAD51-interacting protein whose function has remained elusive. Biochemical and cytological results show that RAD51AP1 functions at a step subsequent to the assembly of the RAD51-ssDNA nucleoprotein filament. Purified RAD51AP1 binds both dsDNA and a D loop structure and, only when able to interact with RAD51, greatly stimulates the RAD51-mediated D loop reaction.
SIGNOR-261962
P01100
O75534
0
post transcriptional regulation
down-regulates quantity
0.295
By testing different classes of mammalian poly(A) nucleases, we identified CCR4 as a poly(A) nuclease involved in the mCRD-mediated rapid deadenylation in viv
SIGNOR-261145
Q9UQM7
Q96PM5
1
phosphorylation
down-regulates
0.296
Phosphorylation of pirh2 by calmodulin-dependent kinase ii impairs its ability to ubiquitinate p53
SIGNOR-156064
Q9H2B2
P45983
0
phosphorylation
up-regulates activity
0.411
JNK phosphorylates Syt 4 at Ser135 in vitro and in vivo.
SIGNOR-273673
P60520
O95352
2
binding
up-regulates activity
0.905
Three human atg8 (hatg8) homologs, lc3, gabarap, and gate-16, have been characterized as modifiers in reactions mediated by hatg7 (an e1-like enzyme) and hatg3 (an e2-like enzyme).
SIGNOR-142002
P56524
Q06413
2
binding
down-regulates
0.713
We discovered that mef2 interacts with histone deacetylases (hdacs) 4 and 5, resulting in repression of the transcriptional activity of mef2.
SIGNOR-76234
P23760
P22455
1
transcriptional regulation
up-regulates quantity by expression
0.365
FGFR4 is a transcriptional target of PAX3 and the PAX3-FOXO1 fusion protein found in ARMS.
SIGNOR-251572
P63096
Q08828
2
binding
down-regulates activity
0.552
GTP-bound, active WT Gαi1 acts to inhibit AC, resulting in a decreased concentration of intracellular cAMP.
SIGNOR-256498
P29597
Q8IU57
2
binding
up-regulates
0.559
Despite signaling through distinct receptor complexes, type i ifns and ifn-_s activate similar signaling events and biological activities, consistent with their common ability to mediate an antiviral state in cells (fig. 6). In both cases, receptor engagement leads via the activation of the jak kinases jak1 and tyk2
SIGNOR-124483
P41240
P12931
1
phosphorylation
down-regulates
0.569
The catalytic activity of the src family of tyrosine kinases is suppressed by phosphorylation on a tyrosine residue located near the c terminus (tyr 527 in c-src), which is catalyzed by c-terminal src kinase (csk).
SIGNOR-179417
O95786
P68400
0
phosphorylation
down-regulates
0.2
Threonine at amino acid (aa) 770 and serine at aa 854 to 855 of rig-i are phosphorylated by casein kinase ii (ck2) in the resting state of the cell and dephosphorylated when cells are infected by rna virus. Mutation at aa position 770 or 854 to 855 of rig-i renders it constitutively active
SIGNOR-169404
Q9NQC7
Q96LD4
0
ubiquitination
down-regulates quantity
0.2
CYLD is progressively degraded upon interaction with the E3 ligase TRIM47 in proportion to NASH severity
SIGNOR-266443
P38398
P30307
1
ubiquitination
down-regulates quantity by destabilization
0.464
BRCA1 mediates cyclin B and Cdc25C ubiquitination.|Thus, BRCA1 dependent proteasomal degradation of cyclin B and Cdc25C precede the subsequent BRCA1 dependent cell cycle arrest.
SIGNOR-278623
P05771
Q96D31
1
phosphorylation
down-regulates
0.2
We propose that pkc suppresses soce and crac channel function by phosphorylation of orai1 at n-terminal serine residues ser-27 and ser-30.
SIGNOR-166040
P49767
P35916
2
binding
up-regulates
0.935
Vegf-c, was isolated as a ligand for the tyrosine kinase vegfr-3 (flt4)
SIGNOR-55205
P01871
Q9UPW6
0
transcriptional regulation
up-regulates quantity
0.2
The SATB2 protein was shown to bind MAR sequences flanking the enhancer of the endogenous immunoglobulin μ heavy chain (IgH) gene in vivo, and this binding was found to correlate with an increase in the expression of a transfected rearranged μ wild-type gene
SIGNOR-268933
P29972
P17252
0
phosphorylation
up-regulates
0.2
Activation of protein kinase c (pkc) by 1-oleoyl-2-acetyl-sn-glycerol (oag) induced a marked increase of aqp1-dependent water permeability. This regulation was abolished in mutated aqp1 channels lacking both consensus pkc phosphorylation sites thr(157) and thr(239) (termed aqp1 deltapkc).
SIGNOR-155106
P07195
Q9NXA8
0
deacetylation
up-regulates activity
0.2
In colorectal cancer, SIRT5 binds to lactate dehydrogenase B (LDHB) to deacetylate it at Lysine 329, thereby increasing its enzymatic activity.
SIGNOR-267645
Q9H3R0
P19525
0
phosphorylation
down-regulates quantity by destabilization
0.2
In the absence of Wnt3a, protein kinase R phosphorylated KDM4C at Ser918, inducing KDM4C ubiquitination and degradation.
SIGNOR-277497
P51149
P60484
0
dephosphorylation
up-regulates activity
0.373
PTEN dephosphorylates Rab7 on two conserved residues S72 and Y183, which are necessary for GDP dissociation inhibitor (GDI)-dependent recruitment of Rab7 on to late endosomes and subsequent maturation.
SIGNOR-276960
Q13131
P46527
1
phosphorylation
up-regulates quantity by stabilization
0.267
P27Kip1-Mediated Cell Survival Is Dependent on AMPK-Specific Thr198 Phosphorylation|AMPK-dependent phosphorylation of p27Kip1 on Thr198 promotes p27Kip1 protein stability, resulting in more autophagy and less apoptosis.
SIGNOR-259859
P56524
P49841
0
phosphorylation
down-regulates
0.364
The double mutation of serines 298/302 into alanines, but also the sole mutation of serine 302, abolishes hdac4 phosphorylation by gsk3_we have shown that cells lacking gsk3_ are unable to degrade hdac4 after serum starvation
SIGNOR-170144
P15882
Q15078
2
binding
up-regulates
0.337
_-chimaerin was identified to interact with the p35 activator of cdk5. The complex of _-chimaerin, cdk5 and p35 is enzymatically functional
SIGNOR-123439
Q13884
P53778
2
binding
down-regulates
0.368
Basal localization of the p38g/p-Carm1 complex in muscle stem cells occurs via binding to the dystrophin-glycoprotein complex (DGC) through b1-syntrophin. In dystrophin-deficient muscle stem cells undergoing asymmetric division, p38g/b1-syntrophin interactions are abrogated, resulting in enhanced Carm1 phosphorylation
SIGNOR-255901
Q99497
O60260
0
ubiquitination
down-regulates quantity by destabilization
0.2
Together, these results demonstrate that parkin selectively recognizes and ubiquitinates misfolded DJ-1 in vivo.
SIGNOR-278526
Q9Y463
P61962
2
binding
up-regulates activity
0.728
Two isoforms of DYRK, DYRK1A and DYRK1B, co-immunoprecipitate with HAN11 when coexpressed in COS cells indicating that the proteins interact in mammalian cells. HAN11 might target DYRKs to cytosolic locations for regulation of specific cellular functions.
SIGNOR-260631
P05412
P00519
0
phosphorylation
up-regulates activity
0.526
Active nuclear Abl efficiently phosphorylate c-Jun. After phosphorylation of c-Jun by Abl on Tyr170, both proteins interacted via the SH2 domain of Abl.
SIGNOR-251428
Q8WXI2
P04049
2
binding
up-regulates
0.767
We show cnk2 interacts with raf. cnk2 interacts with the gef domain of rlf and with both the regulatory and catalytic domains of raf. The raf interaction was also mapped to the carboxyl-terminal half of cnk2. Overexpression of cnk2 results in inhibition of the mapk signaling pathway.
SIGNOR-119039
P46937
O15350
2
binding
up-regulates
0.716
Yap also interacts with p73, a p53 family pro-apoptotic transcription factor, to induce expression of genes such as bax, puma and pml.
SIGNOR-175934
Q13323
Q07817
2
binding
down-regulates
0.808
We have identified a novel cellular protein, bik, that interacts with the cellular survival-promoting proteins, bcl-2 and bcl-xl in transient transfection assays, bik promotes cell death in a manner similar to the death-promoting members of the bcl-2 family, bax and bak.
SIGNOR-26453
P06493
P46937
1
phosphorylation
up-regulates activity
0.425
Our evidence suggested that these YAP sites (Ser138, Thr143, and Ser367) were CDK1 phosphorylation sites.|These data demonstrate that the YAP phosphorylation sites Ser138, Thr143, and Ser367 are important for proper mitosis and cytokinesis.
SIGNOR-276587
Q9BYB0
P42261
2
binding
up-regulates quantity
0.2
SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).
SIGNOR-264601
Q04206
P68400
0
phosphorylation
up-regulates activity
0.443
We demonstrate that casein kinase II (CKII) interacts with p65 in vivo and can phosphorylate p65 at serine 529 in vitro. A CKII inhibitor (PD144795) inhibited TNFalpha-induced p65 phosphorylation in vivo. Furthermore, our results indicate that the association between IkappaBalpha and p65 inhibits p65 phosphorylation by CKII and that degradation of IkappaBalpha allows CKII to phosphorylate p65 to increase NF-kappaB transactivation potential. 
SIGNOR-250942
A7KAX9
P04629
0
relocalization
up-regulates
0.602
Grit translocation was regulated by receptor stimulation
SIGNOR-95809
Q16539
O95382
0
phosphorylation
up-regulates activity
0.2
These data indicate that MKK6 phosphorylates p38 MAP kinase on Thr-180 and Tyr-182, the sites of phosphorylation that activate p38 MAP kinase
SIGNOR-260916
Q15172
P19525
0
phosphorylation
up-regulates
0.328
Phosphorylation of serine 28 by pkr promotes mitochondrial localization of b56alpha, because wild-type but not mutant s28a b56alpha promoted mitochondrial pp2a activity.
SIGNOR-181793
O96014
O75581
2
binding
up-regulates activity
0.572
Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.
SIGNOR-131637
P20226
Q12947
2
binding
up-regulates activity
0.408
The human forkhead protein FREAC-2 contains two functionally redundant activation domains and interacts with TBP and TFIIB.
SIGNOR-220373
P37231
Q15596
2
binding
up-regulates
0.77
Collectively, our data provide the first evidence that erbeta-deficiency protects against diet-induced ir and glucose intolerance which involves an augmented ppargamma signaling in adipose tissue. Moreover, our data suggest that the coactivators src1 and tif2 are involved in this interaction.
SIGNOR-179175
Q8IZL8
P04150
1
transcriptional regulation
up-regulates quantity by expression
0.553
MNAR functionally interacts with both NH2- and COOH-terminal GR domains to modulate transactivation
SIGNOR-251681
P09471
O43614
2
binding
up-regulates activity
0.253
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-257008
P00751
P08603
2
binding
down-regulates activity
0.518
As a regulator of the alternative pathway, FH binds to C3b and inhibits the binding of factor B to C3b, acts as a cofactor for the factor I-mediated cleavage of C3b to iC3b (cofactor activity), and accelerates the decay of C3bBb, the alternative pathway C3 convertase (decay-accelerating activity)
SIGNOR-252142
Q9NVI1
O94782
0
deubiquitination
down-regulates activity
0.666
Phosphorylation of FANCI may also turn the ubiquitinated ID complex into a poor substrate for deubiquitination by the USP1–UAF1 complex, resulting in increased levels of monoubiquitinated FANCD2.
SIGNOR-263272