GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 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
P41143	P63096	2	binding	up-regulates activity	0.543	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-256683
P34947	Q9UQL6	1	phosphorylation	down-regulates activity	0.356	GRK5 phosphorylates and promotes the nuclear export of the histone deacetylase, HDAC5.	SIGNOR-279045
Q92997	Q9ULV1	2	binding	up-regulates activity	0.575	Through study of FZD4 and its associated ligand Norrin, we report that a minimum of three residues distal to the KTXXXW motif in the C-terminal tail of Frizzled-4 are essential for DVL recruitment and robust Lef/Tcf-dependent transcriptional activation in response to Norrin.	SIGNOR-258961
Q9H0N0	O43896	0	relocalization	up-regulates quantity	0.245	Here, we identify Bicaudal-D-related protein 1 (BICDR-1) as an effector of the small GTPase Rab6 and key component of the molecular machinery that controls secretory vesicle transport in developing neurons. BICDR-1 interacts with kinesin motor Kif1C, the dynein/dynactin retrograde motor complex, regulates the pericentrosomal localization of Rab6-positive secretory vesicles and is required for neural development in zebrafish. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation.	SIGNOR-266879
O60674	Q8N4C6	2	binding	down-regulates	0.242	We showed that jak2 directly phosphorylates the n-terminus ofnineinwhile the c-terminus ofnineininhibits jak2 kinase activity in vitro.	SIGNOR-205581
P00519	O15350	1	phosphorylation	up-regulates	0.754	C-abl phosphorylates p73 on a tyrosine residue at position 99 both in vitro and in cells that have been exposed to ionizing radiation. Our results show that c-abl stimulates p73-mediated transactivation and apoptosis.	SIGNOR-68931
Q9BZK7	P10275	2	binding	up-regulates	0.393	We showed that tblr1 physically interacts with ar and directly occupies the androgen-response elements of the affected ar target genes in an androgen-dependent manner. / we characterized tblr1 as a coactivator of ar	SIGNOR-203235
P06493	Q9GZV5	1	phosphorylation	down-regulates activity	0.258	We found that TAZ is phosphorylated in vitro and in vivo by the mitotic kinase CDK1 at S90, S105, T326, and T346 during the G2/M phase of the cell cycle. Interestingly, mitotic phosphorylation inactivates TAZ oncogenic activity	SIGNOR-276518
P49841	Q99250	1	phosphorylation	down-regulates activity	0.2	Glycogen synthase kinase 3β (GSK3beta) phosphorylates the Nav1.2C-terminal tail at T1966, suppressing Na+ currents and channel trafficking to the plasma membrane	SIGNOR-275748
Q96EP1	O14965	1	polyubiquitination	down-regulates quantity by destabilization	0.471	Chfr, a mitotic stress checkpoint, plays an important role in cell cycle progression, tumor suppression and the processes that require the E3 ubiquitin ligase activity mediated by the RING finger domain. Chfr stimulates the formation of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins including Plk1 and Aurora A.	SIGNOR-271463
P27361	Q16828	2	phosphorylation	down-regulates	0.855	Phosphorylation of serines 159 and 197 by erk1/2 enhances proteasomal degradation of mkp-3	SIGNOR-132975
P63096	P21462	2	binding	up-regulates activity	0.435	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-256682
P10275	P08238	2	binding	up-regulates activity	0.704	The unliganded AR resides predominately in the cytoplasm as a heteromeric complex with hsp90 and other chaperone proteins. These chaperone proteins maintain AR in a form that is receptive to ligand binding. Regulation of gene expression by androgen-activated AR occurs through receptor nuclear translocation, dimerization, and binding to androgen response elements (AREs) in the DNA of target genes.	SIGNOR-251535
P09874	P08581	0	phosphorylation	up-regulates activity	0.388	Here we show that the receptor tyrosine kinase c-Met associates with and phosphorylates PARP1 at Tyr907 (PARP1 pTyr907 or pY907).\|To address whether c-Met activates PARP1, we exposed MDA-MB-231 cells expressing control shRNA or c-Met shRNA to H 2 O 2 and subjected them to a comet assay to evaluate the extent of DNA damage.	SIGNOR-279470
Q9Y253	Q86YC2	2	binding	up-regulates	0.538	Palb2 and brca2 interact with pol_ and are required to sustain the recruitment of pol_ at blocked replication forks. Palb2 and brca2 stimulate pol_-dependent dna synthesis on d loop substrates	SIGNOR-204541
Q7Z5G4	P01112	1	palmitoylation	up-regulates activity	0.349	Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.	SIGNOR-261351
Q86YT6	Q9UPN4	1	ubiquitination	down-regulates	0.43	We demonstrate that the E3 ubiquitin ligase MIB1 is a new component of centriolar satellites, which interacts with and ubiquitylates AZI1 and PCM1 and suppresses primary cilium formation. Whereas these proteins are degraded prior to the ciliation process, MIB1 appears to maintain its targets in a latent state through inhibitory ubiquitylation that is reversed during ciliogenesis and in response to cell stress.The precise mechanism by which MIB1 inhibits primary cilium formation through ubiquitylation of ciliogenesis-promoting target proteins such as AZI1 and PCM1 remains to be determined.	SIGNOR-272876
Q15796	Q9Y5K5	0	deubiquitination	up-regulates	0.378	Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases	SIGNOR-138876
P35222	Q9UJU2	2	binding	up-regulates activity	0.917	Activated dvl binds and inhibits the phosphorylation of beta catenin by gsk3beta/alfa, blocking beta catenin degradation), so that beta catenin accumulates and translocates to the nucleus, where it interacts with the t cell specific factor (tcf)/lymphoid enhancer binding factor 1 (lef-1) transcription factor and induces the transcription of target genes such as c-jun, c-myc, and cyclin d1	SIGNOR-134219
P68400	Q06265	1	phosphorylation	up-regulates	0.2	Indeed recombinant pmscl1 undergoes ck2-mediated phosphorylation in vitro at various serine residues, including serines 409 and 411, which reside within the phosphosim region. the exchange of hydrophobic core residues or serines 409 and 411 to alanine attenuates binding of sumo to the phosphosim-containing fragment of pmscl1 in a yeast two-hybrid assay	SIGNOR-184031
P49841	Q14596	1	phosphorylation	down-regulates activity	0.428	The autophagy receptor NBR1 (neighbor of BRCA1 gene 1) binds UB/ubiquitin and the autophagosome-conjugated MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) proteins, thereby ensuring ubiquitinated protein degradation\|Here we show that NBR1 is a substrate of GSK3. NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins and their selective autophagic degradation.	SIGNOR-261795
P19086	Q9H1C0	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-257113
P18031	P51692	1	dephosphorylation	down-regulates activity	0.676	A Cytosolic Protein-tyrosine Phosphatase PTP1B Specifically Dephosphorylates and Deactivates Prolactin-activated STAT5a and STAT5b	SIGNOR-248429
Q16620	P12931	0	phosphorylation	up-regulates activity	0.46	Indeed, activated Src can directly phosphorylate recombinant TrkB protein in a cell-free system.\|We found that both exogenous H 2 O 2 and endogenous ROS activate TrkB signaling by a Src family kinase dependent but brain derived neurotrophic factor independent mechanism in cultured rat cortical neurons.	SIGNOR-280130
P00533	P11171	1	phosphorylation	down-regulates	0.4	The phosphorylation site has been localized to the 8-kda domain, which has one tyrosine, tyrosine-418. The 8-kda region is required for the assembly of the spectrin/actin complex, and phosphorylation by egfr reduced the ability of protein 4.1 to promote the assembly of the spectrin/actin/protein 4.1 ternary complex	SIGNOR-20452
P00533	Q9UK17	1	phosphorylation	up-regulates activity	0.2	Our results demonstrate that human atrial I(to) and cloned hKv4.3 channels are modulated by EGFR kinase via phosphorylation of the Y136 residue and by Src-family kinases via phosphorylation of the Y108 residue\|We found that human atrial I(to) was inhibited by the broad-spectrum PTK inhibitor genistein, the selective epidermal growth factor receptor (EGFR) kinase inhibitor AG556, and the Src-family kinases inhibitor PP2.	SIGNOR-275549
Q8N137	P51955	0	phosphorylation	down-regulates activity	0.35	The opposite outcomes in NEK2- and centrobin-depleted cells suggest that NEK2 antagonizes biological functions of centrobin.\|These results suggest that NEK2 phosphorylates specific sites of centrobin, which are distinct from the PLK1 phosphorylation sites.	SIGNOR-279545
Q13541	P06730	2	binding	down-regulates activity	0.939	The rate-limiting factor for translation is eukaryotic translation initiation factor 4E (eIF4E), which is negatively regulated by eIF4E-binding protein 1 (4E-BP1).	SIGNOR-167176
Q13315	Q13362-1	1	phosphorylation	up-regulates activity	0.378	In the present study, we demonstrate that ataxia-telangiectasia mutated (ATM) directly phosphorylates and specifically regulates B56γ3, B56γ2 and B56δ, after DNA damage. We further show that phosphorylation of B56γ3 at Ser510 leads to an increase in B56γ3-PP2A complexes, and direction of PP2A phosphatase activity toward the substrate p53, activating its tumor-suppressive functions. we show that Ser510 phosphorylation significantly enhances the ability of B56γ3 to inhibit cell proliferation and anchorage-independent growth.	SIGNOR-276318
P30305	P17612	0	phosphorylation	up-regulates activity	0.2	Overall, PRKACA may directly phosphorylate CDC25B on Ser321 to control cell cycle progression in mouse-fertilized eggs [ xref ].\|PRKACA phosphorylates and activates CDC25B in fertilized eggs of mice [ xref ].	SIGNOR-280077
P50148	P21918	2	binding	up-regulates activity	0.501	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-257369
P42224	Q8N2W9	2	binding	down-regulates	0.561	First, piasy interacts with stat1 both in vitro and in vivo. The in vivo piasy__stat1 interaction is dependent on cytokine stimulation. Second, piasy can inhibit stat1-mediated gene activation without blocking the dna binding activity of stat1.	SIGNOR-105723
Q13362	P28482	2	binding	down-regulates	0.513	B56-containing pp2a dephosphorylate erk and their activity is controlled by the early gene iex-1 and erk	SIGNOR-144325
O95835	Q14344	0	phosphorylation	down-regulates activity	0.2	These findings suggest that Galpha13 induced phosphorilation of LATS1 at S909 recruits ITCH to trigger LATS1 degradation, leading to EMT-related phenotypes	SIGNOR-278051
O95251	P53350	0	phosphorylation	up-regulates	0.503	Here, we show that the interaction between plk1 and hbo1 is mitosis-specific and that plk1 phosphorylates hbo1 on ser-57 in vitro and in vivo. During mitosis, cdk1 phosphorylates hbo1 on thr-85/88, creating a docking site for plk1 to be recruited. Significantly, the overexpression of hbo1 mutated at the plk1 phosphorylation site (s57a) leads to cell-cycle arrest in the g1/s phase, inhibition of chromatin loading of the minichromosome maintenance (mcm) complex, and a reduced dna replication rate.	SIGNOR-160751
Q96LB1	P19086	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-257327
P24941	Q14207	1	phosphorylation	up-regulates	0.447	Importantly, mutation of cdk2 phosphorylation sites to alanine abrogates the ability of p220 to activate the histone h2b promoter.	SIGNOR-82141
O14901	Q96ST3	2	binding	up-regulates activity	0.487	detailed biochemical and functional analyses have demonstrated that the TIEG2 _-HRM domain interacts specifically with the PAH2 domain of mSin3A to repress transcription. our data suggest the presence of a conserved _-helical repression motif (_-HRM) in the TIEG and BTEB subfamilies of Sp1-like proteins that mediates transcriptional repression activity through interaction with the corepressor mSin3A.	SIGNOR-222344
P25098	Q13371	1	phosphorylation	down-regulates activity	0.2	The phosphorylation of purified phosducin and PhLP by recombinant GRK2 proceeds rapidly and stoichiometrically (0.82 +/- 0.1 and 0.83 +/- 0.09 mol of P (i)/mol of protein, respectively).	SIGNOR-279178
P34998	P63092	2	binding	up-regulates activity	0.494	Previous studies have indicated that CRHR could couple to multiple Galpha proteins including Gs, Gi, and Gq/11 and then go on to induce changes in AC activity and activation of PLC-beta3	SIGNOR-268617
O75385	Q8TEV9	2	binding	down-regulates activity	0.424	While focusing on the role of SMCR8 during autophagy initiation, we found that kinase activity and gene expression of ULK1 are increased upon SMCR8 depletion.	SIGNOR-252029
Q8TAB3	P31644	2	binding	up-regulates quantity by stabilization	0.258	Here, we found that PCDH19 binds the alpha subunits of GABAAR and regulates its surface availability and currents in cultured hippocampal neurons. The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated. Here, we identified a new interaction between PCDH19 and GABAA receptor (GABAAR) alpha subunits in the rat brain. PCDH19 shRNA-mediated downregulation reduces GABAAR surface expression and affects the frequency and kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in cultured hippocampal neurons.	SIGNOR-267219
P01584	P27930	2	binding	down-regulates	0.878	Interleukin-1 (il-1) interacts with cells through two types of binding molecules, il-1 type i receptor (il-1r i) and il-1r ii. Il-1r ii inhibits il-1 activity by acting as a decoy target for il-1	SIGNOR-38302
P10275	P28482	0	phosphorylation	down-regulates	0.511	Map kinase-dependent phosphorylation at ar ser-515 was supported by the decrease in intensity of the slower migrating 23-kda band after treatment with both egf and increasing concentrations of the map kinase inhibitor, u0126	SIGNOR-178718
P18847	Q99612	0	transcriptional regulation	up-regulates quantity by expression	0.394	KLF6 binds directly to and activates the ATF3 promoter.	SIGNOR-266051
P15311	P61586	0	phosphorylation	up-regulates activity	0.76	Rev-erbα interacted with OPHN-1, promoted RhoA activity and phosphorylation of ERM. etection of phosphorylated ezrin (Thr567)/radixin (Thr564)/moesin (Thr558)(p-ERM) in Rev-erbαfl/flCre− and Rev-erbαfl/flPF4Cre+ platelets using phospho-specific antibodies.	SIGNOR-268429
P10071	Q9UMX1	2	binding	up-regulates quantity by stabilization	0.889	We show that loss of suppressor of fused (Sufu; an inhibitory effector for Gli proteins) results in destabilization of Gli2 and Gli3 full-length activators but not of their C-terminally processed repressors, whereas overexpression of Sufu stabilizes them.	SIGNOR-268868
P38405	Q9NVN3	2	binding	up-regulates activity	0.492	In the olfactory sensory neurons located in the nasal epithelium, OR activation by odorants or other stimuli can switch on a specific olfactory G-protein (GNAL), which in turn stimulatesand ADCY3 and Ric8b leads to cyclic adenosine monophosphate (cAMP) generation from adenosine triphosphate (ATP)	SIGNOR-278071
P43026	Q13253	2	binding	down-regulates activity	0.688	Growth and differentiation factor 5 (GDF5), a member of the bone morphogenetic protein (BMP) family, is essential for cartilage, bone, and joint formation. Antagonists such as noggin counteract BMP signaling by covering the ligand's BMP type I (BMPRI) and type II (BMPRII, ActRII, ActRIIB) interaction sites. The mutation GDF5-S94N is located within the BMPRII interaction site, the so-called knuckle epitope, and was identified in patients suffering from multiple synostoses syndrome (SYNS).	SIGNOR-252420
Q86VB7	P67870	0	phosphorylation	up-regulates activity	0.307	Interaction of CD163 with the regulatory subunit of casein kinase II (CKII) and dependence of CD163 signaling on CKII and protein kinase C. \| Inhibition studies using specific kinase inhibitors reveal that both CKII and PKC are involved in the CD163 signaling mechanism resulting in the secretion of proinflammatory cytokines.	SIGNOR-251056
P15172	Q13207	2	binding	down-regulates activity	0.31	We have found that TBX2 is highly up regulated in both ERMS and ARMS subtypes of RMS and demonstrate that TBX2 is a repressor of myogenesis by binding to MyoD and myogenin and inhibiting their activity.	SIGNOR-251560
P63000	O14827	0	guanine nucleotide exchange factor	up-regulates activity	0.498	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-260574
P06493	P56181	1	phosphorylation	up-regulates activity	0.2	Here, we show that a fraction of cyclin B1/Cdk1 proteins localizes to the matrix of mitochondria and phosphorylates a cluster of mitochondrial proteins, including the complex I (CI) subunits in the respiratory chain. Cyclin B1/Cdk1-mediated CI phosphorylation enhances CI activity, whereas deficiency of such phosphorylation in each of the relevant CI subunits results in impairment of CI function.\|These results were confirmed by generating phosphorylation defective forms of the five CI subunits through substitutions of S/T residues with Alanine (A) on either Cdk1 optimal or minimal consensus motifs (T383 on NDUFV1, S105 on NDUFV3, S364 on NDUFS2, S55/S29/T5 on NDUFB6, and T142/T120 on NDUFA12). The mutation of Cdk1 consensus motifs severely diminished their phosphorylation	SIGNOR-275593
Q13043	Q9H2K8	0	phosphorylation	up-regulates	0.283	In addition, the thousand-and-one (tao) amino acids kinase or taok13 has been shown to directly phosphorylate and activate hpo or mst1/2	SIGNOR-192762
P19086	P25021	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-257317
P06493	Q13950	1	phosphorylation	up-regulates	0.479	In vitro kinase assays using recombinant cdc2 kinase showed that runx2 was phosphorylated at ser(451) the cdc2 inhibitor roscovitine dose dependently inhibited in vivo runx2 dna-binding activity during mitosis and the runx2 mutant s451a exhibited lower dna-binding activity and reduced stimulation of anchorage-independent growth relative to wild type runx2.	SIGNOR-143586
O43663	Q00536	0	phosphorylation	up-regulates activity	0.344	Mechanistically, CDK16 exerts its function by phosphorylating protein regulator of cytokinesis 1 (PRC1) to regulate spindle formation during mitosis.\|Indeed, immunoblot analysis showed that PRC1 phosphorylation at the T481 site (CDK-dependent major phosphorylation site) fluctuated with the abundance of CDK16 protein in the cell cycle process	SIGNOR-273017
P08069	O00443	1	phosphorylation	up-regulates	0.275	Analysis of the ability of the full-length igfr and its mutant receptors described above to associate with phosphatidylinositol 3 kinase indicated that the association required ptk activity and tyrosine [?] Phosphorylation of the receptors and correlated well with their transforming activities	SIGNOR-32076
P35408	P63096	2	binding	up-regulates activity	0.312	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-257032
P53350	Q00987	1	phosphorylation	up-regulates	0.465	Here we show that the oncogenic and cell cycle-regulatory protein kinase, polo-like kinase-1 (plk1), phosphorylates mdm2 at one of these residues, ser260, and stimulates mdm2-mediated turnover of p53. These data are consistent with the idea that deregulation of plk1 during tumourigenesis may help suppress p53 function.	SIGNOR-94272
P52732	Q9ULW0	2	binding	down-regulates activity	0.499	Dimeric, but not monomeric, Eg5 was differentially inhibited by full-length and truncated TPX2, demonstrating that dimerization or residues in the neck region are important for the interaction of TPX2 with Eg5.	SIGNOR-265097
Q9UNE7	O15519	1	ubiquitination	down-regulates quantity by destabilization	0.356	Taken together, our data suggest that CHIP interacts with c-FLIP L in vivo and promotes the ubiquitination of c-FLIP L.\|When we knocked down CHIP, c-FLIP L degradation was inhibited after treatment with 17-AAG, which indicated that CHIP modulated c-FLIP L degradation in the NSCLC cell lines.	SIGNOR-278783
P46937	Q15562	2	binding	up-regulates	0.884	When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead14.	SIGNOR-201468
Q13158	Q15628	2	binding	up-regulates activity	0.781	Tradd recruits fadd	SIGNOR-177958
Q86V86	Q13200	1	phosphorylation	up-regulates activity	0.2	Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B).	SIGNOR-273897
Q99558	P50281	1	phosphorylation	up-regulates activity	0.2	A post-transcriptional process is indicated because we observed that NIK increases MT1-MMP phosphorylation and activity, but does not affect MT1-MMP mRNA expression (XREF_FIG and XREF_FIG).\|NIK increases MT1-MMP pseudopodial localization and enzymatic activity.	SIGNOR-279631
O95944	Q8IZD2-8	2	binding	up-regulates activity	0.505	We identify natural cytotoxicity receptor NKp44 (NKp44L), a novel isoform of the mixed-lineage leukemia-5 protein, as a cellular ligand for NKp44. Unlike the other MLL family members, NKp44L is excluded from the nucleus, but expressed at the cell-surface level; its subcellular localization is being associated with the presence of a specific C-terminal motif. Strikingly, NKp44L has not been detected on circulating cells isolated from healthy individuals, but it is expressed on a large panel of the tumor and transformed cells.	SIGNOR-260042
Q96T60	Q13315	0	phosphorylation	up-regulates	0.462	We demonstrate that pnkp is phosphorylated by the dna-dependent protein kinase (dna-pk) and ataxia-telangiectasia mutated (atm) in vitro. The major phosphorylation site for both kinases was serine 114, with serine 126 being a minor site. Purified pnkp protein with mutation of serines 114 and 126 had decreased dna kinase and dna phosphatase activities and reduced affinity for dna in vitro.	SIGNOR-176008
Q5VWQ8	P01116	1	gtpase-activating protein	down-regulates activity	0.518	The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP hydrolysis to GDP.	SIGNOR-254746
Q01968	P20339	2	binding	up-regulates activity	0.696	We report that Rab5 acts at the plasma membrane, downstream of ruffling, to promote macropinosome sealing and scission. Rab5 is recruited to plasmalemmal circular ruffles before macropinosome closure. Rab5 effectors Inpp5b, OCRL and APPL1 localize to macropinocytic cups and vesicles, and are required for macropinosome sealing. The mammalian 5-phosphatases Inpp5b and OCRL, which can degrade PtdIns(4,5)P2, are both Rab5-associating effectors implicated in endocytosis and macropinocytosis	SIGNOR-277771
P56704	Q5T9L3	0	relocalization	up-regulates activity	0.641	WNT secretion requires its binding to the carrier protein wntless (WLS);	SIGNOR-256599
Q14289	Q05209	0	dephosphorylation	down-regulates activity	0.544	Inhibition of the catalytic activity of cell adhesion kinase beta by protein-tyrosine phosphatase-pest-mediated dephosphorylation. / dephosphorylation of tyr402 and tyr579/580 by ptp-pest	SIGNOR-107502
P40763	Q9Y6X2	0	sumoylation	down-regulates	0.731	Stat3 mediated signaling pathways can be inhibited by pias3 (protein inhibitor of activated stat3), which was recently found to regulate protein stability and function by its sumo (small-ubiquitin like modifiers) ligase activity in promoting sumoylation of important nuclear proteins.	SIGNOR-124723
Q9Y2N7	O60260	0	ubiquitination	down-regulates quantity by destabilization	0.2	Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ubiquitination to occur.	SIGNOR-263089
P08670	Q9H0X6	0	ubiquitination	down-regulates quantity by destabilization	0.2	Here, we show that RING finger protein 208 (RNF208) decreases the stability of soluble Vimentin protein through a polyubiquitin-mediated proteasomal degradation pathway, thereby suppressing metastasis of TNBC cells	SIGNOR-269051
Q13627	P46527	1	phosphorylation	up-regulates activity	0.332	DYRK1A phosphorylates p27 Kip1 at Ser10 in primary neurons and in vivo.\|Thus, our results identify DYRK1A as the predominant kinase that phosphorylates and stabilizes p27Kip1 during neuronal differentiation.	SIGNOR-278250
Q9H1C0	P08754	2	binding	up-regulates activity	0.419	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-256861
P10721	P10721	2	phosphorylation	up-regulates	0.2	Identification of tyr-703 and tyr-936 as autophosphorylation sites in c-kit/scfr	SIGNOR-68643
P55317	P10275	1	transcriptional regulation	down-regulates quantity by repression	0.766	FOXA1 directly inhibits AR expression and thus the transcription of its target genes. FOXA1 inhibits AR gene expression in prostate cancer. oss of FOXA1 may lead to androgen-independent AR signaling and thus castration-resistant prostate cancer progression. Indeed, we have recently reported that FOXA1 is downregulated in CRPC	SIGNOR-251541
P0DP23	P16298	2	binding	up-regulates	0.696	Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain.	SIGNOR-114101
P17844	P04637	2	binding	up-regulates	0.702	The dead box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor	SIGNOR-133341
Q13627	Q14814	1	phosphorylation	down-regulates activity	0.411	DYRK1A phosphorylates MEF2D and decreases its transcriptional activity	SIGNOR-277901
P17612	P19793	1	phosphorylation	down-regulates	0.2	Serine 27, a human retinoid x receptor alpha residue, phosphorylated by protein kinase a is essential for cyclicamp-mediated downregulation of rxralpha function.	SIGNOR-104954
Q9NY61	O96017	0	phosphorylation	up-regulates quantity by stabilization	0.358	Three putative Chk2 phosphorylation sites (Stevens et al., 2003) are present in Che-1 at resides Ser141, Ser474, and Ser508. Thus, we performed in vitro Chk2 kinase assays utilizing the GST-Che-1 fusion peptides spanning these residues as substrates.\| Taken together, these results indicate that Chk2 phosphorylates Che-1 and this phosphorylation contributes to increase Che-1 stability.	SIGNOR-264416
P04350	Q14980	2	binding	up-regulates	0.402	Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.	SIGNOR-117025
P20827	P54756	2	binding	up-regulates	0.811	Ephrin-a1 binds and activates the tyrosine kinase activity of eph-a2, and has a dissociation constant of 20_30 nm. ephrin-a1 interacts with all the other epha subclass receptors as well, although with different affinity	SIGNOR-56910
Q16621	Q96J02	0	ubiquitination	down-regulates activity	0.413	Itch regulates p45/NF-E2 in vivo by Lys63-linked ubiquitination\| Interestingly, Itch suppressed the transactivation activity of p45/NF-E2 by adding a Lys63-linked polyubiquitin chain. Confocal microscopy revealed that ubiquitinated p45/NF-E2 became localized in the cytoplasm when Itch was over-expressed. Thus, Itch-mediated ubiquitination of p45/NF-E2 does not target the protein for proteasomal degradation, but instead retains p45/NF-E2 in the cytoplasm, where it cannot function as a transactivator.	SIGNOR-275553
Q8NBF1	P41221	1	transcriptional regulation	up-regulates quantity by expression	0.248	GLIS1, a novel hypoxia-inducible transcription factor, promotes breast cancer cell motility via activation of WNT5A	SIGNOR-269040
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
P07202	Q06710	0	transcriptional regulation	up-regulates quantity by expression	0.399	TSH regulates TPO expression through the cAMP pathway and acts with thyroid-specific transcription factors such as TTF-1, TTF-2 and Pax-8.	SIGNOR-267277
Q06413	Q92585	2	binding	up-regulates	0.393	Unexpectedly, however, emerging evidence implicate maml proteins as exciting key transcriptional co-activators in other signal transduction pathways including: muscle differentiation and myopathies (mef2c), tumor suppressor pathway (p53) and colon carcinoma survival (beta-catenin).	SIGNOR-144913
P49841	Q15910	1	phosphorylation	down-regulates activity	0.33	GSK3beta phosphorylates EZH2 at Ser363 and Thr367 in vitro, and activating GSK3beta upregulates Thr367 phosphorylationin vivo.	SIGNOR-278176
P53805	Q5S007	0	phosphorylation	up-regulates activity	0.371	LRRK2 Directly Phosphorylates RCAN1.	SIGNOR-278340
Q15582	Q13118	0	transcriptional regulation	up-regulates quantity by expression	0.242	Analyzing the mechanism of TGFBI up-regulation in clear cell carcinoma, we identified a novel VHL target, a Kruppel-like transcriptional factor 10 (KLF10). The TGFBI promoter, which we isolated and studied in Luc-reporter assay, was induced by KLF10 but not hypoxia.	SIGNOR-253212
P12931	P09619	0	phosphorylation	up-regulates activity	0.604	The increased Src activity is mainly due to the phosphorylation of Tyr-419, rather than the dephosphorylation of Tyr-530 of Src protein. PDGFR, not FAK or EGFR, appears to be the upstream protein tyrosine kinase responsible for the detachment-induced Src activation in the lung tumor cells.	SIGNOR-247979
O96004	P17612	0	phosphorylation	down-regulates activity	0.296	In vitro and in vivo phosphorylation studies show that both PKA and PKC can phosphorylate HAND1 and -2. T107; S109 within helix I and S98 within the basic domain, are the phosphorylated residues. We determined that modification of HAND1 at residues 107 and 109 affects dimerization affinities with E-proteins, thus changing the bHLH dimer equilibrium within the cell. These modifications also affect HAND1 function.	SIGNOR-249991
Q96S53	P60981	1	phosphorylation	down-regulates activity	0.422	The present study provides evidence that TESK2 can phosphorylate cofilin and ADF specifically at Ser-3. Since actin-depolymerizing and -severing activities of cofilin/ADF are abrogated by phosphorylation at Ser-3, TESK2 seems to play an important role in actin filament dynamics by inhibiting cofilin/ADF activity.	SIGNOR-246707
Q99459	Q9UNY4	2	binding	up-regulates quantity by stabilization	0.432	HLodestar/HuF2 associates with CDC5L in cell lysates and HeLa nuclear extracts. It is possible that during the cell division cycle, hLodestar/HuF2s associates with transcription/splicing complexes in order to inhibit transcription/splicing prior to the start of mitosis and/or functions in stabilizing nuclear complexes containing splicing factors (e.g., the CDC5L complex) so that these are available for re-initiation of splicing at the end of mitosis when gene expression is re-established in cells.	SIGNOR-224460
Q86XR7	Q8IUC6	2	binding	up-regulates activity	0.586	Tram binds trif directly and recruits it to tlr4	SIGNOR-118367
P31749	P13631	1	phosphorylation	up-regulates activity	0.467	S379 of RARγ is indispensable for the CLDN6-triggered cellular events. The most important finding of the present study is that the CLDN6/SFK/PI3K/AKT signaling controls the RARγ and ERα activities (Fig. 6).	SIGNOR-277492

P41143

P63096

2

binding

up-regulates activity

0.543

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-256683

P34947

Q9UQL6

1

phosphorylation

down-regulates activity

0.356

GRK5 phosphorylates and promotes the nuclear export of the histone deacetylase, HDAC5.

SIGNOR-279045

Q92997

Q9ULV1

2

binding

up-regulates activity

0.575

Through study of FZD4 and its associated ligand Norrin, we report that a minimum of three residues distal to the KTXXXW motif in the C-terminal tail of Frizzled-4 are essential for DVL recruitment and robust Lef/Tcf-dependent transcriptional activation in response to Norrin.

SIGNOR-258961

Q9H0N0

O43896

0

relocalization

up-regulates quantity

0.245

Here, we identify Bicaudal-D-related protein 1 (BICDR-1) as an effector of the small GTPase Rab6 and key component of the molecular machinery that controls secretory vesicle transport in developing neurons. BICDR-1 interacts with kinesin motor Kif1C, the dynein/dynactin retrograde motor complex, regulates the pericentrosomal localization of Rab6-positive secretory vesicles and is required for neural development in zebrafish. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation.

SIGNOR-266879

O60674

Q8N4C6

2

binding

down-regulates

0.242

We showed that jak2 directly phosphorylates the n-terminus ofnineinwhile the c-terminus ofnineininhibits jak2 kinase activity in vitro.

SIGNOR-205581

P00519

O15350

1

phosphorylation

up-regulates

0.754

C-abl phosphorylates p73 on a tyrosine residue at position 99 both in vitro and in cells that have been exposed to ionizing radiation. Our results show that c-abl stimulates p73-mediated transactivation and apoptosis.

SIGNOR-68931

Q9BZK7

P10275

2

binding

up-regulates

0.393

We showed that tblr1 physically interacts with ar and directly occupies the androgen-response elements of the affected ar target genes in an androgen-dependent manner. / we characterized tblr1 as a coactivator of ar

SIGNOR-203235

P06493

Q9GZV5

1

phosphorylation

down-regulates activity

0.258

We found that TAZ is phosphorylated in vitro and in vivo by the mitotic kinase CDK1 at S90, S105, T326, and T346 during the G2/M phase of the cell cycle. Interestingly, mitotic phosphorylation inactivates TAZ oncogenic activity

SIGNOR-276518

P49841

Q99250

1

phosphorylation

down-regulates activity

0.2

Glycogen synthase kinase 3β (GSK3beta) phosphorylates the Nav1.2C-terminal tail at T1966, suppressing Na+ currents and channel trafficking to the plasma membrane

SIGNOR-275748

Q96EP1

O14965

1

polyubiquitination

down-regulates quantity by destabilization

0.471

Chfr, a mitotic stress checkpoint, plays an important role in cell cycle progression, tumor suppression and the processes that require the E3 ubiquitin ligase activity mediated by the RING finger domain. Chfr stimulates the formation of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins including Plk1 and Aurora A.

SIGNOR-271463

P27361

Q16828

2

phosphorylation

down-regulates

0.855

Phosphorylation of serines 159 and 197 by erk1/2 enhances proteasomal degradation of mkp-3

SIGNOR-132975

P63096

P21462

2

binding

up-regulates activity

0.435

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-256682

P10275

P08238

2

binding

up-regulates activity

0.704

The unliganded AR resides predominately in the cytoplasm as a heteromeric complex with hsp90 and other chaperone proteins. These chaperone proteins maintain AR in a form that is receptive to ligand binding. Regulation of gene expression by androgen-activated AR occurs through receptor nuclear translocation, dimerization, and binding to androgen response elements (AREs) in the DNA of target genes.

SIGNOR-251535

P09874

P08581

0

phosphorylation

up-regulates activity

0.388

Here we show that the receptor tyrosine kinase c-Met associates with and phosphorylates PARP1 at Tyr907 (PARP1 pTyr907 or pY907).|To address whether c-Met activates PARP1, we exposed MDA-MB-231 cells expressing control shRNA or c-Met shRNA to H 2 O 2 and subjected them to a comet assay to evaluate the extent of DNA damage.

SIGNOR-279470

Q9Y253

Q86YC2

2

binding

up-regulates

0.538

Palb2 and brca2 interact with pol_ and are required to sustain the recruitment of pol_ at blocked replication forks. Palb2 and brca2 stimulate pol_-dependent dna synthesis on d loop substrates

SIGNOR-204541

Q7Z5G4

P01112

1

palmitoylation

up-regulates activity

0.349

Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.

SIGNOR-261351

Q86YT6

Q9UPN4

1

ubiquitination

down-regulates

0.43

We demonstrate that the E3 ubiquitin ligase MIB1 is a new component of centriolar satellites, which interacts with and ubiquitylates AZI1 and PCM1 and suppresses primary cilium formation. Whereas these proteins are degraded prior to the ciliation process, MIB1 appears to maintain its targets in a latent state through inhibitory ubiquitylation that is reversed during ciliogenesis and in response to cell stress.The precise mechanism by which MIB1 inhibits primary cilium formation through ubiquitylation of ciliogenesis-promoting target proteins such as AZI1 and PCM1 remains to be determined.

SIGNOR-272876

Q15796

Q9Y5K5

0

deubiquitination

up-regulates

0.378

Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases

SIGNOR-138876

P35222

Q9UJU2

2

binding

up-regulates activity

0.917

Activated dvl binds and inhibits the phosphorylation of beta catenin by gsk3beta/alfa, blocking beta catenin degradation), so that beta catenin accumulates and translocates to the nucleus, where it interacts with the t cell specific factor (tcf)/lymphoid enhancer binding factor 1 (lef-1) transcription factor and induces the transcription of target genes such as c-jun, c-myc, and cyclin d1

SIGNOR-134219

P68400

Q06265

1

phosphorylation

up-regulates

0.2

Indeed recombinant pmscl1 undergoes ck2-mediated phosphorylation in vitro at various serine residues, including serines 409 and 411, which reside within the phosphosim region. the exchange of hydrophobic core residues or serines 409 and 411 to alanine attenuates binding of sumo to the phosphosim-containing fragment of pmscl1 in a yeast two-hybrid assay

SIGNOR-184031

P49841

Q14596

1

phosphorylation

down-regulates activity

0.428

The autophagy receptor NBR1 (neighbor of BRCA1 gene 1) binds UB/ubiquitin and the autophagosome-conjugated MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) proteins, thereby ensuring ubiquitinated protein degradation|Here we show that NBR1 is a substrate of GSK3. NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins and their selective autophagic degradation.

SIGNOR-261795

P19086

Q9H1C0

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-257113

P18031

P51692

1

dephosphorylation

down-regulates activity

0.676

A Cytosolic Protein-tyrosine Phosphatase PTP1B Specifically Dephosphorylates and Deactivates Prolactin-activated STAT5a and STAT5b

SIGNOR-248429

Q16620

P12931

0

phosphorylation

up-regulates activity

0.46

Indeed, activated Src can directly phosphorylate recombinant TrkB protein in a cell-free system.|We found that both exogenous H 2 O 2 and endogenous ROS activate TrkB signaling by a Src family kinase dependent but brain derived neurotrophic factor independent mechanism in cultured rat cortical neurons.

SIGNOR-280130

P00533

P11171

1

phosphorylation

down-regulates

0.4

The phosphorylation site has been localized to the 8-kda domain, which has one tyrosine, tyrosine-418. The 8-kda region is required for the assembly of the spectrin/actin complex, and phosphorylation by egfr reduced the ability of protein 4.1 to promote the assembly of the spectrin/actin/protein 4.1 ternary complex

SIGNOR-20452

P00533

Q9UK17

1

phosphorylation

up-regulates activity

0.2

Our results demonstrate that human atrial I(to) and cloned hKv4.3 channels are modulated by EGFR kinase via phosphorylation of the Y136 residue and by Src-family kinases via phosphorylation of the Y108 residue|We found that human atrial I(to) was inhibited by the broad-spectrum PTK inhibitor genistein, the selective epidermal growth factor receptor (EGFR) kinase inhibitor AG556, and the Src-family kinases inhibitor PP2.

SIGNOR-275549

Q8N137

P51955

0

phosphorylation

down-regulates activity

0.35

The opposite outcomes in NEK2- and centrobin-depleted cells suggest that NEK2 antagonizes biological functions of centrobin.|These results suggest that NEK2 phosphorylates specific sites of centrobin, which are distinct from the PLK1 phosphorylation sites.

SIGNOR-279545

Q13541

P06730

2

binding

down-regulates activity

0.939

The rate-limiting factor for translation is eukaryotic translation initiation factor 4E (eIF4E), which is negatively regulated by eIF4E-binding protein 1 (4E-BP1).

SIGNOR-167176

Q13315

Q13362-1

1

phosphorylation

up-regulates activity

0.378

In the present study, we demonstrate that ataxia-telangiectasia mutated (ATM) directly phosphorylates and specifically regulates B56γ3, B56γ2 and B56δ, after DNA damage. We further show that phosphorylation of B56γ3 at Ser510 leads to an increase in B56γ3-PP2A complexes, and direction of PP2A phosphatase activity toward the substrate p53, activating its tumor-suppressive functions. we show that Ser510 phosphorylation significantly enhances the ability of B56γ3 to inhibit cell proliferation and anchorage-independent growth.

SIGNOR-276318

P30305

P17612

0

phosphorylation

up-regulates activity

0.2

Overall, PRKACA may directly phosphorylate CDC25B on Ser321 to control cell cycle progression in mouse-fertilized eggs [ xref ].|PRKACA phosphorylates and activates CDC25B in fertilized eggs of mice [ xref ].

SIGNOR-280077

P50148

P21918

2

binding

up-regulates activity

0.501

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-257369

P42224

Q8N2W9

2

binding

down-regulates

0.561

First, piasy interacts with stat1 both in vitro and in vivo. The in vivo piasy__stat1 interaction is dependent on cytokine stimulation. Second, piasy can inhibit stat1-mediated gene activation without blocking the dna binding activity of stat1.

SIGNOR-105723

Q13362

P28482

2

binding

down-regulates

0.513

B56-containing pp2a dephosphorylate erk and their activity is controlled by the early gene iex-1 and erk

SIGNOR-144325

O95835

Q14344

0

phosphorylation

down-regulates activity

0.2

These findings suggest that Galpha13 induced phosphorilation of LATS1 at S909 recruits ITCH to trigger LATS1 degradation, leading to EMT-related phenotypes

SIGNOR-278051

O95251

P53350

0

phosphorylation

up-regulates

0.503

Here, we show that the interaction between plk1 and hbo1 is mitosis-specific and that plk1 phosphorylates hbo1 on ser-57 in vitro and in vivo. During mitosis, cdk1 phosphorylates hbo1 on thr-85/88, creating a docking site for plk1 to be recruited. Significantly, the overexpression of hbo1 mutated at the plk1 phosphorylation site (s57a) leads to cell-cycle arrest in the g1/s phase, inhibition of chromatin loading of the minichromosome maintenance (mcm) complex, and a reduced dna replication rate.

SIGNOR-160751

Q96LB1

P19086

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-257327

P24941

Q14207

1

phosphorylation

up-regulates

0.447

Importantly, mutation of cdk2 phosphorylation sites to alanine abrogates the ability of p220 to activate the histone h2b promoter.

SIGNOR-82141

O14901

Q96ST3

2

binding

up-regulates activity

0.487

detailed biochemical and functional analyses have demonstrated that the TIEG2 _-HRM domain interacts specifically with the PAH2 domain of mSin3A to repress transcription. our data suggest the presence of a conserved _-helical repression motif (_-HRM) in the TIEG and BTEB subfamilies of Sp1-like proteins that mediates transcriptional repression activity through interaction with the corepressor mSin3A.

SIGNOR-222344

P25098

Q13371

1

phosphorylation

down-regulates activity

0.2

The phosphorylation of purified phosducin and PhLP by recombinant GRK2 proceeds rapidly and stoichiometrically (0.82 +/- 0.1 and 0.83 +/- 0.09 mol of P (i)/mol of protein, respectively).

SIGNOR-279178

P34998

P63092

2

binding

up-regulates activity

0.494

Previous studies have indicated that CRHR could couple to multiple Galpha proteins including Gs, Gi, and Gq/11 and then go on to induce changes in AC activity and activation of PLC-beta3

SIGNOR-268617

O75385

Q8TEV9

2

binding

down-regulates activity

0.424

While focusing on the role of SMCR8 during autophagy initiation, we found that kinase activity and gene expression of ULK1 are increased upon SMCR8 depletion.

SIGNOR-252029

Q8TAB3

P31644

2

binding

up-regulates quantity by stabilization

0.258

Here, we found that PCDH19 binds the alpha subunits of GABAAR and regulates its surface availability and currents in cultured hippocampal neurons. The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated. Here, we identified a new interaction between PCDH19 and GABAA receptor (GABAAR) alpha subunits in the rat brain. PCDH19 shRNA-mediated downregulation reduces GABAAR surface expression and affects the frequency and kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in cultured hippocampal neurons.

SIGNOR-267219

P01584

P27930

2

binding

down-regulates

0.878

Interleukin-1 (il-1) interacts with cells through two types of binding molecules, il-1 type i receptor (il-1r i) and il-1r ii. Il-1r ii inhibits il-1 activity by acting as a decoy target for il-1

SIGNOR-38302

P10275

P28482

0

phosphorylation

down-regulates

0.511

Map kinase-dependent phosphorylation at ar ser-515 was supported by the decrease in intensity of the slower migrating 23-kda band after treatment with both egf and increasing concentrations of the map kinase inhibitor, u0126

SIGNOR-178718

P18847

Q99612

0

transcriptional regulation

up-regulates quantity by expression

0.394

KLF6 binds directly to and activates the ATF3 promoter.

SIGNOR-266051

P15311

P61586

0

phosphorylation

up-regulates activity

0.76

Rev-erbα interacted with OPHN-1, promoted RhoA activity and phosphorylation of ERM. etection of phosphorylated ezrin (Thr567)/radixin (Thr564)/moesin (Thr558)(p-ERM) in Rev-erbαfl/flCre− and Rev-erbαfl/flPF4Cre+ platelets using phospho-specific antibodies.

SIGNOR-268429

P10071

Q9UMX1

2

binding

up-regulates quantity by stabilization

0.889

We show that loss of suppressor of fused (Sufu; an inhibitory effector for Gli proteins) results in destabilization of Gli2 and Gli3 full-length activators but not of their C-terminally processed repressors, whereas overexpression of Sufu stabilizes them.

SIGNOR-268868

P38405

Q9NVN3

2

binding

up-regulates activity

0.492

In the olfactory sensory neurons located in the nasal epithelium, OR activation by odorants or other stimuli can switch on a specific olfactory G-protein (GNAL), which in turn stimulatesand ADCY3 and Ric8b leads to cyclic adenosine monophosphate (cAMP) generation from adenosine triphosphate (ATP)

SIGNOR-278071

P43026

Q13253

2

binding

down-regulates activity

0.688

Growth and differentiation factor 5 (GDF5), a member of the bone morphogenetic protein (BMP) family, is essential for cartilage, bone, and joint formation. Antagonists such as noggin counteract BMP signaling by covering the ligand's BMP type I (BMPRI) and type II (BMPRII, ActRII, ActRIIB) interaction sites. The mutation GDF5-S94N is located within the BMPRII interaction site, the so-called knuckle epitope, and was identified in patients suffering from multiple synostoses syndrome (SYNS).

SIGNOR-252420

Q86VB7

P67870

0

phosphorylation

up-regulates activity

0.307

Interaction of CD163 with the regulatory subunit of casein kinase II (CKII) and dependence of CD163 signaling on CKII and protein kinase C. | Inhibition studies using specific kinase inhibitors reveal that both CKII and PKC are involved in the CD163 signaling mechanism resulting in the secretion of proinflammatory cytokines.

SIGNOR-251056

P15172

Q13207

2

binding

down-regulates activity

0.31

We have found that TBX2 is highly up regulated in both ERMS and ARMS subtypes of RMS and demonstrate that TBX2 is a repressor of myogenesis by binding to MyoD and myogenin and inhibiting their activity.

SIGNOR-251560

P63000

O14827

0

guanine nucleotide exchange factor

up-regulates activity

0.498

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-260574

P06493

P56181

1

phosphorylation

up-regulates activity

0.2

Here, we show that a fraction of cyclin B1/Cdk1 proteins localizes to the matrix of mitochondria and phosphorylates a cluster of mitochondrial proteins, including the complex I (CI) subunits in the respiratory chain. Cyclin B1/Cdk1-mediated CI phosphorylation enhances CI activity, whereas deficiency of such phosphorylation in each of the relevant CI subunits results in impairment of CI function.|These results were confirmed by generating phosphorylation defective forms of the five CI subunits through substitutions of S/T residues with Alanine (A) on either Cdk1 optimal or minimal consensus motifs (T383 on NDUFV1, S105 on NDUFV3, S364 on NDUFS2, S55/S29/T5 on NDUFB6, and T142/T120 on NDUFA12). The mutation of Cdk1 consensus motifs severely diminished their phosphorylation

SIGNOR-275593

Q13043

Q9H2K8

0

phosphorylation

up-regulates

0.283

In addition, the thousand-and-one (tao) amino acids kinase or taok13 has been shown to directly phosphorylate and activate hpo or mst1/2

SIGNOR-192762

P19086

P25021

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-257317

P06493

Q13950

1

phosphorylation

up-regulates

0.479

In vitro kinase assays using recombinant cdc2 kinase showed that runx2 was phosphorylated at ser(451) the cdc2 inhibitor roscovitine dose dependently inhibited in vivo runx2 dna-binding activity during mitosis and the runx2 mutant s451a exhibited lower dna-binding activity and reduced stimulation of anchorage-independent growth relative to wild type runx2.

SIGNOR-143586

O43663

Q00536

0

phosphorylation

up-regulates activity

0.344

Mechanistically, CDK16 exerts its function by phosphorylating protein regulator of cytokinesis 1 (PRC1) to regulate spindle formation during mitosis.|Indeed, immunoblot analysis showed that PRC1 phosphorylation at the T481 site (CDK-dependent major phosphorylation site) fluctuated with the abundance of CDK16 protein in the cell cycle process

SIGNOR-273017

P08069

O00443

1

phosphorylation

up-regulates

0.275

Analysis of the ability of the full-length igfr and its mutant receptors described above to associate with phosphatidylinositol 3 kinase indicated that the association required ptk activity and tyrosine [?] Phosphorylation of the receptors and correlated well with their transforming activities

SIGNOR-32076

P35408

P63096

2

binding

up-regulates activity

0.312

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-257032

P53350

Q00987

1

phosphorylation

up-regulates

0.465

Here we show that the oncogenic and cell cycle-regulatory protein kinase, polo-like kinase-1 (plk1), phosphorylates mdm2 at one of these residues, ser260, and stimulates mdm2-mediated turnover of p53. These data are consistent with the idea that deregulation of plk1 during tumourigenesis may help suppress p53 function.

SIGNOR-94272

P52732

Q9ULW0

2

binding

down-regulates activity

0.499

Dimeric, but not monomeric, Eg5 was differentially inhibited by full-length and truncated TPX2, demonstrating that dimerization or residues in the neck region are important for the interaction of TPX2 with Eg5.

SIGNOR-265097

Q9UNE7

O15519

1

ubiquitination

down-regulates quantity by destabilization

0.356

Taken together, our data suggest that CHIP interacts with c-FLIP L in vivo and promotes the ubiquitination of c-FLIP L.|When we knocked down CHIP, c-FLIP L degradation was inhibited after treatment with 17-AAG, which indicated that CHIP modulated c-FLIP L degradation in the NSCLC cell lines.

SIGNOR-278783

P46937

Q15562

2

binding

up-regulates

0.884

When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead14.

SIGNOR-201468

Q13158

Q15628

2

binding

up-regulates activity

0.781

Tradd recruits fadd

SIGNOR-177958

Q86V86

Q13200

1

phosphorylation

up-regulates activity

0.2

Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B).

SIGNOR-273897

Q99558

P50281

1

phosphorylation

up-regulates activity

0.2

A post-transcriptional process is indicated because we observed that NIK increases MT1-MMP phosphorylation and activity, but does not affect MT1-MMP mRNA expression (XREF_FIG and XREF_FIG).|NIK increases MT1-MMP pseudopodial localization and enzymatic activity.

SIGNOR-279631

O95944

Q8IZD2-8

2

binding

up-regulates activity

0.505

We identify natural cytotoxicity receptor NKp44 (NKp44L), a novel isoform of the mixed-lineage leukemia-5 protein, as a cellular ligand for NKp44. Unlike the other MLL family members, NKp44L is excluded from the nucleus, but expressed at the cell-surface level; its subcellular localization is being associated with the presence of a specific C-terminal motif. Strikingly, NKp44L has not been detected on circulating cells isolated from healthy individuals, but it is expressed on a large panel of the tumor and transformed cells.

SIGNOR-260042

Q96T60

Q13315

0

phosphorylation

up-regulates

0.462

We demonstrate that pnkp is phosphorylated by the dna-dependent protein kinase (dna-pk) and ataxia-telangiectasia mutated (atm) in vitro. The major phosphorylation site for both kinases was serine 114, with serine 126 being a minor site. Purified pnkp protein with mutation of serines 114 and 126 had decreased dna kinase and dna phosphatase activities and reduced affinity for dna in vitro.

SIGNOR-176008

Q5VWQ8

P01116

1

gtpase-activating protein

down-regulates activity

0.518

The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP hydrolysis to GDP.

SIGNOR-254746

Q01968

P20339

2

binding

up-regulates activity

0.696

We report that Rab5 acts at the plasma membrane, downstream of ruffling, to promote macropinosome sealing and scission. Rab5 is recruited to plasmalemmal circular ruffles before macropinosome closure. Rab5 effectors Inpp5b, OCRL and APPL1 localize to macropinocytic cups and vesicles, and are required for macropinosome sealing. The mammalian 5-phosphatases Inpp5b and OCRL, which can degrade PtdIns(4,5)P2, are both Rab5-associating effectors implicated in endocytosis and macropinocytosis

SIGNOR-277771

P56704

Q5T9L3

0

relocalization

up-regulates activity

0.641

WNT secretion requires its binding to the carrier protein wntless (WLS);

SIGNOR-256599

Q14289

Q05209

0

dephosphorylation

down-regulates activity

0.544

Inhibition of the catalytic activity of cell adhesion kinase beta by protein-tyrosine phosphatase-pest-mediated dephosphorylation. / dephosphorylation of tyr402 and tyr579/580 by ptp-pest

SIGNOR-107502

P40763

Q9Y6X2

0

sumoylation

down-regulates

0.731

Stat3 mediated signaling pathways can be inhibited by pias3 (protein inhibitor of activated stat3), which was recently found to regulate protein stability and function by its sumo (small-ubiquitin like modifiers) ligase activity in promoting sumoylation of important nuclear proteins.

SIGNOR-124723

Q9Y2N7

O60260

0

ubiquitination

down-regulates quantity by destabilization

0.2

Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ubiquitination to occur.

SIGNOR-263089

P08670

Q9H0X6

0

ubiquitination

down-regulates quantity by destabilization

0.2

Here, we show that RING finger protein 208 (RNF208) decreases the stability of soluble Vimentin protein through a polyubiquitin-mediated proteasomal degradation pathway, thereby suppressing metastasis of TNBC cells

SIGNOR-269051

Q13627

P46527

1

phosphorylation

up-regulates activity

0.332

DYRK1A phosphorylates p27 Kip1 at Ser10 in primary neurons and in vivo.|Thus, our results identify DYRK1A as the predominant kinase that phosphorylates and stabilizes p27Kip1 during neuronal differentiation.

SIGNOR-278250

Q9H1C0

P08754

2

binding

up-regulates activity

0.419

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-256861

P10721

2

phosphorylation

up-regulates

0.2

Identification of tyr-703 and tyr-936 as autophosphorylation sites in c-kit/scfr

SIGNOR-68643

P55317

P10275

1

transcriptional regulation

down-regulates quantity by repression

0.766

FOXA1 directly inhibits AR expression and thus the transcription of its target genes. FOXA1 inhibits AR gene expression in prostate cancer. oss of FOXA1 may lead to androgen-independent AR signaling and thus castration-resistant prostate cancer progression. Indeed, we have recently reported that FOXA1 is downregulated in CRPC

SIGNOR-251541

P0DP23

P16298

2

binding

up-regulates

0.696

Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain.

SIGNOR-114101

P17844

P04637

2

binding

up-regulates

0.702

The dead box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor

SIGNOR-133341

Q13627

Q14814

1

phosphorylation

down-regulates activity

0.411

DYRK1A phosphorylates MEF2D and decreases its transcriptional activity

SIGNOR-277901

P17612

P19793

1

phosphorylation

down-regulates

0.2

Serine 27, a human retinoid x receptor alpha residue, phosphorylated by protein kinase a is essential for cyclicamp-mediated downregulation of rxralpha function.

SIGNOR-104954

Q9NY61

O96017

0

phosphorylation

up-regulates quantity by stabilization

0.358

Three putative Chk2 phosphorylation sites (Stevens et al., 2003) are present in Che-1 at resides Ser141, Ser474, and Ser508. Thus, we performed in vitro Chk2 kinase assays utilizing the GST-Che-1 fusion peptides spanning these residues as substrates.| Taken together, these results indicate that Chk2 phosphorylates Che-1 and this phosphorylation contributes to increase Che-1 stability.

SIGNOR-264416

P04350

Q14980

2

binding

up-regulates

0.402

Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.

SIGNOR-117025

P20827

P54756

2

binding

up-regulates

0.811

Ephrin-a1 binds and activates the tyrosine kinase activity of eph-a2, and has a dissociation constant of 20_30 nm. ephrin-a1 interacts with all the other epha subclass receptors as well, although with different affinity

SIGNOR-56910

Q16621

Q96J02

0

ubiquitination

down-regulates activity

0.413

Itch regulates p45/NF-E2 in vivo by Lys63-linked ubiquitination| Interestingly, Itch suppressed the transactivation activity of p45/NF-E2 by adding a Lys63-linked polyubiquitin chain. Confocal microscopy revealed that ubiquitinated p45/NF-E2 became localized in the cytoplasm when Itch was over-expressed. Thus, Itch-mediated ubiquitination of p45/NF-E2 does not target the protein for proteasomal degradation, but instead retains p45/NF-E2 in the cytoplasm, where it cannot function as a transactivator.

SIGNOR-275553

Q8NBF1

P41221

1

transcriptional regulation

up-regulates quantity by expression

0.248

GLIS1, a novel hypoxia-inducible transcription factor, promotes breast cancer cell motility via activation of WNT5A

SIGNOR-269040

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

P07202

Q06710

0

transcriptional regulation

up-regulates quantity by expression

0.399

TSH regulates TPO expression through the cAMP pathway and acts with thyroid-specific transcription factors such as TTF-1, TTF-2 and Pax-8.

SIGNOR-267277

Q06413

Q92585

2

binding

up-regulates

0.393

Unexpectedly, however, emerging evidence implicate maml proteins as exciting key transcriptional co-activators in other signal transduction pathways including: muscle differentiation and myopathies (mef2c), tumor suppressor pathway (p53) and colon carcinoma survival (beta-catenin).

SIGNOR-144913

P49841

Q15910

1

phosphorylation

down-regulates activity

0.33

GSK3beta phosphorylates EZH2 at Ser363 and Thr367 in vitro, and activating GSK3beta upregulates Thr367 phosphorylationin vivo.

SIGNOR-278176

P53805

Q5S007

0

phosphorylation

up-regulates activity

0.371

LRRK2 Directly Phosphorylates RCAN1.

SIGNOR-278340

Q15582

Q13118

0

transcriptional regulation

up-regulates quantity by expression

0.242

Analyzing the mechanism of TGFBI up-regulation in clear cell carcinoma, we identified a novel VHL target, a Kruppel-like transcriptional factor 10 (KLF10). The TGFBI promoter, which we isolated and studied in Luc-reporter assay, was induced by KLF10 but not hypoxia.

SIGNOR-253212

P12931

P09619

0

phosphorylation

up-regulates activity

0.604

The increased Src activity is mainly due to the phosphorylation of Tyr-419, rather than the dephosphorylation of Tyr-530 of Src protein. PDGFR, not FAK or EGFR, appears to be the upstream protein tyrosine kinase responsible for the detachment-induced Src activation in the lung tumor cells.

SIGNOR-247979

O96004

P17612

0

phosphorylation

down-regulates activity

0.296

In vitro and in vivo phosphorylation studies show that both PKA and PKC can phosphorylate HAND1 and -2. T107; S109 within helix I and S98 within the basic domain, are the phosphorylated residues. We determined that modification of HAND1 at residues 107 and 109 affects dimerization affinities with E-proteins, thus changing the bHLH dimer equilibrium within the cell. These modifications also affect HAND1 function.

SIGNOR-249991

Q96S53

P60981

1

phosphorylation

down-regulates activity

0.422

The present study provides evidence that TESK2 can phosphorylate cofilin and ADF specifically at Ser-3. Since actin-depolymerizing and -severing activities of cofilin/ADF are abrogated by phosphorylation at Ser-3, TESK2 seems to play an important role in actin filament dynamics by inhibiting cofilin/ADF activity.

SIGNOR-246707

Q99459

Q9UNY4

2

binding

up-regulates quantity by stabilization

0.432

HLodestar/HuF2 associates with CDC5L in cell lysates and HeLa nuclear extracts. It is possible that during the cell division cycle, hLodestar/HuF2s associates with transcription/splicing complexes in order to inhibit transcription/splicing prior to the start of mitosis and/or functions in stabilizing nuclear complexes containing splicing factors (e.g., the CDC5L complex) so that these are available for re-initiation of splicing at the end of mitosis when gene expression is re-established in cells.

SIGNOR-224460

Q86XR7

Q8IUC6

2

binding

up-regulates activity

0.586

Tram binds trif directly and recruits it to tlr4

SIGNOR-118367

P31749

P13631

1

phosphorylation

up-regulates activity

0.467

S379 of RARγ is indispensable for the CLDN6-triggered cellular events. The most important finding of the present study is that the CLDN6/SFK/PI3K/AKT signaling controls the RARγ and ERα activities (Fig. 6).

SIGNOR-277492