GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q13332	P98160	binding	up-regulates	0.253	We demonstrate here that cptpsigma is a heparin-binding protein and that its basal lamina ligands include the heparan sulfate proteoglycans (hspgs) agrin and collagen xviii.	SIGNOR-115246
P19086	P08912	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-257125
Q99704	O14920	phosphorylation	up-regulates	0.253	Ikkbeta phosphorylates dok1 s(439)s(443) and s(446)s(450) after tnf-alpha, il-1, or gamma-radiation. mutant dok1 a(439), a(443), a(446), and a(450) differed from wild-type dok1 in not inhibiting platelet-derived growth factor-induced extracellular signal-regulated kinase 1/2 phosphorylation or cell growth. Mutant dok1 a(439), a(443), a(446), and a(450) also did not promote cell motility whereas wild-type dok1 promoted cell motility.	SIGNOR-131447
Q9UQD0	Q92914	binding	down-regulates activity	0.253	Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.	SIGNOR-253414
P30305	Q15418	phosphorylation	up-regulates	0.253	Rsk promotes g2/m transition through activating phosphorylation of cdc25a and cdc25b rsk is likely to be more active in mitotic cells than in interphase cells, as evidenced by the phosphorylation status of t359/s363 in rsk. Together, these findings indicate that rsk promotes g2/m transition in mammalian cells through activating phosphorylation of cdc25a and cdc25b.	SIGNOR-202125
P35968	P23470	dephosphorylation	down-regulates activity	0.253	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254707
P09471	O43614	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
P19086	P28566	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-257100
P36776	P31749	phosphorylation	up-regulates activity	0.253	In mitochondria, LonP1 is phosphorylated by Akt on Ser173 and Ser181, enhancing its protease activity.	SIGNOR-265724
Q09472	Q9UK32	phosphorylation	down-regulates activity	0.253	Figure 2G shows that Ser89 phosphorylation of p300, an event that inhibits p300’s acetyltransferase activity (13), was decreased in RSK4-silenced A549 and T24 cells. Consequently, RSK4 may regulate the activity of the NFκB pathway by direct phosphorylation of p300, as recombinant RSK4 phosphorylates p300 on Ser89 in vitro	SIGNOR-275796
P43405	P00519	phosphorylation	up-regulates activity	0.253	Abl kinases modulate Syk kinase activation.\|Expression of constitutively active Abl (AblPP) increased Syk Y346 phosphorylation, whereas the phosphorylation was unaffected in cells expressing kinase inactive form of Abl (AblKR) (XREF_FIG).	SIGNOR-279665
P09471	Q13639	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-257242
Q96LC9	P28482	phosphorylation	up-regulates	0.253	Phosphomimetic mutation of this site (s74d) moderately enhanced bmf apoptotic activity in vivo.22 here, we demonstrate a previously unrecognized mode of regulation of bmf. We show that b-raf-mek-erk2 signaling regulates bmf phosphorylation at serine 74 and serine 77. Phosphorylation of serine 77 downregulates the pro-apoptotic activity of bmf.	SIGNOR-195475
Q9H1B7	Q12947	transcriptional regulation	up-regulates quantity by expression	0.253	FOXF2 directly bound the promoter of E3 ligase interferon regulatory factor 2-binding protein-like (IRF2BPL) and induced its transcriptional expression. IRF2BPL in turn interacted with β-catenin, increasing its ubiquitination and degradation.	SIGNOR-267152
Q9UK80	Q16539	phosphorylation	up-regulates activity	0.253	In this study, we found that USP21 is an important deubiquitinating enzyme for STING and that it negatively regulates the DNA virus-induced production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STING. HSV-1 infection recruited USP21 to STING at late stage by p38-mediated phosphorylation of USP21 at Ser538. I	SIGNOR-273670
Q9HC35	Q9HC98	phosphorylation	up-regulates activity	0.253	The mitotic kinases NEK6 and NEK7 phosphorylated the EML4 N-terminal domain at Ser144 and Ser146 in vitro, and depletion of these kinases in cells led to increased EML4 binding to microtubules in mitosis. An S144A-S146A double mutant not only bound inappropriately to mitotic microtubules but also increased their stability and interfered with chromosome congression. In addition, constitutive activation of NEK6 or NEK7 reduced the association of EML4 with interphase microtubules. Together, these data support a model in which NEK6- and NEK7-dependent phosphorylation promotes the dissociation of EML4 from microtubules in mitosis in a manner that is required for efficient chromosome congression.	SIGNOR-273883
Q14847	P12931	phosphorylation	up-regulates activity	0.253	Integrin-dependent translocation of LASP-1 to the cytoskeleton of activated platelets correlates with LASP-1 phosphorylation at tyrosine 171 by Src-kinase	SIGNOR-271706
Q99683	Q9H2G2	phosphorylation	up-regulates	0.253	Induction of apoptosis by the ste20-like kinase slk, a germinal center kinase that activates apoptosis signal-regulating kinase and p38	SIGNOR-142665
P19086	P21554	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-257119
P69905	P09601	null	down-regulates activity	0.253	Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regulates cellular hemoprotein, hemoglobin, and heme	SIGNOR-251813
P17252	Q6ZVD8	dephosphorylation	down-regulates quantity	0.253	In addition, knockdown of PHLPP expression reduces the rate of phorbol ester-triggered dephosphorylation of the hydrophobic motif, but not turn motif, of PKC alpha	SIGNOR-237051
P05198	Q9Y6E2	binding	up-regulates activity	0.253	BZW2, as an evolutionary highly conserved protein, interacts with eIF2 and eIF3 and promotes ternary complex formation in vitro	SIGNOR-261220
P36639	Q13309	binding	down-regulates quantity by destabilization	0.253	Here, we report that MTH1 is regulated by polyubiquitination mediated by the E3 ligase Skp2. In melanoma cells, MTH1 was upregulated commonly mainly due to its improved stability caused by K63-linked polyubiquitination. Although Skp2 along with other components of the Skp1-Cullin-F-box (SCF) ubiquitin ligase complex was physically associated with MTH1, blocking the SCF function ablated MTH1 ubiquitination and expression. Conversely, overexpressing Skp2-elevated levels of MTH1 associated with an increase in its K63-linked ubiquitination.	SIGNOR-272790
P98177	Q99576	relocalization	down-regulates activity	0.253	GILZ inhibits FOXO1, FOXO3, and FOXO4 transcriptional activities measured with natural or synthetic FOXO-responsive promoters in HL-60 cells.	SIGNOR-256148
P35499	Q92913	binding	down-regulates activity	0.252	Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.	SIGNOR-253431
P09471	P50406	binding	up-regulates activity	0.252	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-257186
P19086	P32245	binding	up-regulates activity	0.252	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-257270
P48775	P43694	transcriptional regulation	down-regulates quantity by repression	0.252	GATA4 inhibits expression of the tryptophan oxygenase gene by binding to the TATA box in fetal hepatocytes.	SIGNOR-268994
Q08499	P27361	phosphorylation	down-regulates	0.252	These straddle the target residue, ser(579), for erk2 phosphorylation of pde4d3. Mutation of either or both of these docking sites prevented erk2 from being co-immunoprecipitated with pde4d3, ablated the ability of epidermal growth factor to inhibit pde4d3 through erk2 action in transfected cos cells, and attenuated the ability of erk2 to phosphorylate pde4d3 in vitro.	SIGNOR-77578
Q14694	Q13315	phosphorylation	up-regulates quantity by stabilization	0.252	The translocation and stabilization of USP10 is regulated by ATM -mediated phosphorylation of USP10 at Thr42 and Ser337.	SIGNOR-276276
O96013	O94806	phosphorylation	up-regulates activity	0.252	PAK4 activity is regulated by an autoinhibitory domain that is released upon RhoGTPase binding as well as phosphorylation at Ser474 in the activation loop of the kinase domain. In the present study, we add another level of complexity to PAK4 regulation by showing that phosphorylation at Ser99 is required for its targeting to the leading edge. This phosphorylation is mediated by PKD1 (protein kinase D1)	SIGNOR-275931
P53350	Q9UNE7	ubiquitination	down-regulates quantity by destabilization	0.252	As indicated in xref , all three Plk1 fragments were ubiquitinated by CHIP, suggesting that CHIP targets multiple sites of Plk1 for ubiquitination.\|Mechanistically, CHIP mediated degradation of AR and Plk1 leads to enhanced efficacy of HSP90 inhibitors.	SIGNOR-278532
O94768	Q15139	phosphorylation	up-regulates activity	0.252	Coexpression of DRAK2 and a constitutively active PKD mutant (CA-PKD1; PKD1-S738/742E) were sufficient to greatly enhance DRAK2 autophosphorylation, supporting the hypothesis that PKD catalytic activity promotes DRAK2 function.\|We note that PKD was able to phosphorylate DRAK2 outside of its C terminus, suggesting that PKD mediated phosphorylation occurs on a site in the 1-290 fragment of DRAK2.	SIGNOR-279753
Q99250	Q92914	binding	down-regulates activity	0.252	Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.	SIGNOR-253430
Q14315	Q4L180	binding	down-regulates quantity by destabilization	0.252	We identified the extended basophilic phosphosite motif RxRxxp[S/T]xxp[S/T] in various proteins including filamin-C (FLNc). Importantly, this extended motif, located in a unique insert in Ig-like domain 20 of FLNc, is doubly phosphorylated. The protein kinases responsible for this dual-site phosphorylation are Akt and PKCα. Proximity proteomics and interaction analysis identified filamin A-interacting protein 1 (FILIP1) as direct FLNc binding partner. FILIP1 binding induces filamin degradation, thereby negatively regulating its function. Here, dual-site phosphorylation of FLNc not only reduces FILIP1 binding, providing a mechanism to shield FLNc from FILIP1-mediated degradation, but also enables fast dynamics of FLNc necessary for its function as signaling adaptor in cross-striated muscle cells.	SIGNOR-262618
P14416	P41732	binding	down-regulates quantity	0.252	Tetraspanin-7 (TSPAN7) is expressed to variable degrees in different tissues, with the highest level in the brain, and multiple mutations in TSPAN7 have been implicated in intellectual disability. Our results showed that TSPAN7 was associated with DRD2 and reduced its surface expression by enhancing DRD2 internalization.Finally, TSPAN7 negatively affects DRD2-mediated signaling.	SIGNOR-265557
P42224	O00141	phosphorylation	up-regulates activity	0.252	Notably, A\u03b2-activated SGK1 or JAK2 kinase phosphorylates STAT1 and induces its association with Tau(1\u2013368).	SIGNOR-279281
Q9UHA4	P85298	binding	up-regulates activity	0.252	Furthermore, we identify that BPGAP1 (a BCH domain-containing, Cdc42GAP-like Rho GTPase-activating protein) promotes MEK partner 1 (MP1)-induced ERK activation on late endosome through scaffolding MP1/MEK1 complex. This regulatory function requires phosphorylation of BPGAP1 by JNK at its C terminal tail (Ser424) to unlock its autoinhibitory conformation.	SIGNOR-275551
O96013	Q15139	phosphorylation	up-regulates activity	0.252	When PKD3 was knocked-down using isoform-specific shRNA (PKD3-shRNA), PAK4 activity (judged by its phosphorylation status at the activation loop using the pS474-PAK4 antibody) was decreased	SIGNOR-275930
P35354	P11831	null	up-regulates	0.252	Srf within myofibers modulates Il6 and Cox2/Il4 expressions and, therefore, exerts a paracrine control of satellite cell proliferation and fusion, respectively, which in turn support skeletal muscle hypertrophy.	SIGNOR-255965
Q8TCU6	Q8WXX7	binding	up-regulates activity	0.252	Mutations in the Autism susceptibility candidate 2 gene (AUTS2), whose protein is believed to act in neuronal cell nuclei, have been associated with multiple psychiatric illnesses, including autism spectrum disorders, intellectual disability, and schizophrenia. Here we show that cytoplasmic AUTS2 is involved in the regulation of the cytoskeleton and neural development. AUTS2 activates Rac1 to induce lamellipodia but downregulates Cdc42 to suppress filopodia. Our loss-of-function and rescue experiments show that a cytoplasmic AUTS2-Rac1 pathway is involved in cortical neuronal migration and neuritogenesis in the developing brain. These results suggest that FL-AUTS2 can activate Rac1 via interaction with P-Rex1 and the Elmo2/Dock180 complex to regulate actin dynamics in N1E-115 cells.	SIGNOR-266817
Q9Y2I6	Q96GD4	phosphorylation	up-regulates	0.252	Importantly, nlp is characterized as a novel substrate of aurora b and can be phosphorylated by aurora b. The specific phosphorylation sites are mapped at ser-185, ser-448, and ser-585. The phosphorylation at ser-448 and ser-585 is likely required for nlp association with aurora b and localization at midbody. Meanwhile, the phosphorylation at ser-185 is vital to nlp protein stability. Disruptions of these phosphorylation sites abolish cytokinesis and lead to chromosomal instability.	SIGNOR-168053
P19086	Q9Y5X5	binding	up-regulates activity	0.252	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-257104
P17947	O15550	transcriptional regulation	down-regulates quantity by repression	0.252	Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase	SIGNOR-260036
Q9NZ72	P49840	phosphorylation	up-regulates activity	0.252	Altogether, these results indicate that CDK5 phosphorylates similarly serines 68 and 73, whereas ERK2 targets mostly serine 68 and GSK-3beta mostly serine 60.\|This observation may support the hypothesis of a specific localization of stathmin 3 depending on its phosphorylation by GSK-3beta	SIGNOR-264883
P04271	O43248	transcriptional regulation	up-regulates quantity by expression	0.252	HOXC6 and HOXC11 increase transcription of S100beta gene in BrdU-induced in vitro differentiation of GOTO neuroblastoma cells into Schwannian cells.	SIGNOR-261647
P38936	Q92945	post transcriptional regulation	down-regulates quantity by destabilization	0.252	Importantly, KSRP knockdown in C2C12 GM cells (Figure 2D) stabilized endogenous my- ogenin and p21 transcripts (Figure 2E). Furthermore, stable knockdown of KSRP, using shRNA, induced the accumulation of p21 mRNA in C2C12 GM while it did not affect the expression of late myogenic markers (MHC and muscle-creatine kinase [MCK])	SIGNOR-235859
P63096	P32238	binding	up-regulates activity	0.252	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-257035
P61006	O43318	phosphorylation	up-regulates activity	0.252	In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. \|Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.\|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease	SIGNOR-260266
P07101	Q99742	transcriptional regulation	down-regulates quantity by repression	0.252	Overexpression and siRNA experiments revealed that NPAS1, in concert with ARNT, negatively regulates the expression of TH and that this regulation is mediated by a direct binding of NPAS1 on the TH promoter.	SIGNOR-253702
P08754	P32238	binding	up-regulates activity	0.252	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-257148
Q9UNS1	P04150	transcriptional regulation	up-regulates quantity by expression	0.252	GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription	SIGNOR-268052
P19086	Q9GZQ6	binding	up-regulates activity	0.252	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-257103
P35372	P04843	binding	up-regulates	0.252	Ribophorin i (rpni), a component of the oligosaccharide transferase complex, could directly interact with mor. Rpni can be shown to participate in mor export by the intracellular retention of the receptor after small interfering rna knockdown of endogenous rpni.	SIGNOR-184651
P09471	P32238	binding	up-regulates activity	0.252	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-257236
P68363	Q5SQI0	acetylation	up-regulates quantity by stabilization	0.252	Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.\|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules	SIGNOR-272245
P19086	P41146	binding	up-regulates activity	0.252	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-257117
P55075	P40425	transcriptional regulation	down-regulates quantity by repression	0.251	Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription	SIGNOR-265778
P52565	Q9ULL4	binding	up-regulates activity	0.251	Here, we report the expression of plexin-B3 in glioma cells, which upon stimulation by its ligand Sema5A results in significant inhibition of cell migration and invasion. A search for the underlying mechanism revealed direct interaction of plexin-B3 with RhoGDP dissociation inhibitor α (RhoGDIα), a negative regulator of RhoGTPases that blocks guanine nucleotide exchange and sequesters them away from the plasma membrane. direct interaction of RhoGDIα and the cytoplasmic domain of plexin-B3 (plexin-B3CD) was confirmed by GST pulldown assays.	SIGNOR-268435
P45973	Q9C0F0	binding	down-regulates activity	0.251	Here, we showed that ASXL3 interacts with HP1α and LSD1, leading to transcriptional repression.	SIGNOR-266763
P23588	Q14004	phosphorylation	up-regulates activity	0.251	CDK13 directly phosphorylates 4E-BP1 at Thr46 and eIF4B at Ser422; genetically or pharmacologically inhibiting CDK13 disrupts mRNA translation.	SIGNOR-273115
Q9HAW8	P20823	transcriptional regulation	up-regulates quantity by expression	0.251	Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter.	SIGNOR-253971
Q9NPD5	P20823	transcriptional regulation	up-regulates quantity by expression	0.251	Farnesoid X receptor, hepatocyte nuclear factors 1alpha and 3beta are essential for transcriptional activation of the liver-specific organic anion transporter-2 gene.\|This study demonstrated that the transcription of the LST-2 gene is regulated by three transcription factors, FXR, HNF1alpha, and HNF3beta.	SIGNOR-268988
O95817	Q05655	phosphorylation	up-regulates	0.251	Pkc_-mediated phosphorylation of bag3 at ser187 site induces epithelial-mesenchymal transition and enhances invasiveness in thyroid cancer fro cells. we showed that bag3 was implicated in epithelial-mesenchymal transition (emt) procedure, and phosphorylation state at ser187 site had a critical role in emt regulation by bag3.	SIGNOR-199316
P31941	Q13617	ubiquitination	down-regulates quantity by destabilization	0.251	Human Papillomavirus 16 E7 Stabilizes APOBEC3A Protein by Inhibiting Cullin 2-Dependent Protein Degradation\|Here, we report that the HPV oncoprotein E7 stabilizes the APOBEC3A (A3A) protein in human keratinocytes by inhibiting ubiquitin-dependent protein degradation in a cullin-dependent manner.	SIGNOR-261325
Q92997	Q8IZQ1	relocalization	down-regulates quantity by destabilization	0.251	Our data taken together with the known role of ALFY in autophagy, demonstrate specific targeting and autophagy-mediated removal of DVL3 by hALFY.	SIGNOR-266793
Q76N32	P51955	phosphorylation	down-regulates quantity by destabilization	0.251	In this study we show phosphorylation of Cep68 by Nek2 creates a potential phosphodegron that directs Cep68 destruction through the activity of SCF-beta-Trcp.\|Our above results showed that Nek2 promoted mitotic degradation of Cep68.	SIGNOR-279471
P48664	P35398	transcriptional regulation	up-regulates quantity by expression	0.251	RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.	SIGNOR-266850
P35869	P53350	phosphorylation	down-regulates activity	0.251	In this study, we demonstrate that PLK1 phosphorylates AHR at S489 in LUAD, leading to epithelial-mesenchymal transition (EMT) and metastatic events.	SIGNOR-277885
Q15465	P35398	transcriptional regulation	up-regulates quantity by expression	0.251	RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.	SIGNOR-266846
P49716	Q9P2J3	binding	down-regulates quantity by destabilization	0.251	KLHL9 mediates poly-ubiquitylation of C/EBPβ and C/EBPδ isoforms. We confirmed KLHL9 deletions in an independent cohort and showed that this protein is necessary for Cul3-ligase mediated ubiquitylation and proteasomal degradation of established MES-GBM MRs, C/EBPβ and C/EBPδ.	SIGNOR-272459
P35247	P17676	transcriptional regulation	up-regulates quantity by expression	0.251	Cotransfection of C/EBPalpha, C/EBPbeta, or C/EBPdelta cDNA in H441 lung adenocarcinoma cells significantly increased the luciferase activity of a wild-type SP-D promoter construct containing 698 bp of upstream sequence (SS698). Transfection of C/EBP also increased the level of endogenous SP-D mRNA in H441 cells\| Thus, interactions among C/EBP elements in the near-distal promoter can modulate the promoter activity of SP-D.	SIGNOR-254045
P05198	Q92879	binding	up-regulates activity	0.251	These studies showed that both the increased levels of CUGBP1 and cdk4-mediated hyper-phosphorylation of CUGBP1 are involved in the age-associated induction of the CUGBP1-eIF2 complex. The CUGBP1-eIF2 complex is bound to C/EBPbeta mRNA in the liver of old animals, and this binding correlates with the increased amounts of liver-enriched activator protein and liver-enriched inhibitory protein.	SIGNOR-262736
P40763	O43683	phosphorylation	up-regulates activity	0.251	This study showed that the BUB1 kinase drives the progression and proliferation of BCa by regulating the transcriptional activation of STAT3 signaling and may be an attractive candidate for therapeutic targeting in BCa.\|We further identified through a series of molecular and cell biological approaches that BUB1 interacted directly with STAT3 and mediated the phosphorylation of STAT3 at Ser727.	SIGNOR-280198
Q9Y625	O95644	transcriptional regulation	up-regulates quantity by expression	0.251	NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype.	SIGNOR-264022
P55085	Q15661	binding	up-regulates activity	0.251	Mast cells contribute to tissue repair in fibrous tissues by stimulating proliferation of fibroblasts through the release of tryptase which activates protease-activated receptor-2 (PAR-2).\|Taken together, our data show that tryptase can stimulate myoblast proliferation and this effect is part of a signaling cascade dependent on PAR-2 activation and on the downstream activation of COX-2.	SIGNOR-251744
Q05397	P16591	phosphorylation	up-regulates activity	0.251	The Fer mediated phosphorylation of specific tyrosine residues of FAK was abolished by cotransfection of shRNA against Fer (i.e., shFer), but not by control shRNA, indicating that the phosphorylation of Tyr577, 861, or 925 of FAK in suspended cells was indeed caused by Fer.	SIGNOR-279409
O95433	P00519	phosphorylation	up-regulates activity	0.251	Here, we show that c-Abl kinase phosphorylates Y223 in human Aha1 (hAha1), promoting its interaction with Hsp90. This, consequently, results in an increased Hsp90 ATPase activity	SIGNOR-260938
P03372	Q9Y5X4	transcriptional regulation	up-regulates quantity by expression	0.251	NR2E3 directly regulates expression of ESR1 \| Furthermore, overexpression of exogenous NR2E3 further increased expression of ESR1 and its downstream targets as well as its transcriptional activity in MCF-7 cells (Fig S1 of Supporting Information), strongly demonstrating that NR2E3 regulates ESR1 expression and subsequent ESR1-mediated induction of target genes.	SIGNOR-266207
P10451	P15036	transcriptional regulation	up-regulates quantity by expression	0.251	We demonstrated that Ets2 is capable of binding to and transactivating the OPN promoter using gel shift and transient transfection assays	SIGNOR-259872
Q15031	P18848	transcriptional regulation	up-regulates quantity by expression	0.251	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269421
O60716	P17252	phosphorylation	down-regulates activity	0.251	PKC\u03b1 phosphorylation of p120 at S879 is a critical phospho-switch mediating disassociation of p120 from VE-cadherin that results in AJ disassembly.\|We surmised that PKCalpha may function to disrupt AJs by signaling dissociation of p120 from VE-cadherin.	SIGNOR-278261
Q14344	P30989	binding	up-regulates activity	0.25	Altogether, these results reveal for the first time the ability of hNTS1 to directly activate the Gαq-, Gαi1-, GαoA-, and Gα13-mediated signaling pathways	SIGNOR-278060
P19484	Q8IVH8	phosphorylation	down-regulates activity	0.25	However, although our results indicate that MAP4K3 initiates TFEB repression, MAP4K3 also promotes robust mTORC1 activation upon amino acid stimulation - ; hence, MAP4K3 and mTORC1 must ultimately work together to achieve robust suppression of autophagy.\|Moreover, MAP4K3 serine 3 phosphorylation of TFEB is required for TFEB interaction with mTORC1-Rag GTPase-Ragulator complex and TFEB cytosolic sequestration.	SIGNOR-278282
P50148	Q13639	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-257367
Q92974	Q96GD4	phosphorylation	down-regulates activity	0.25	The mitotic kinases Aurora A/B and Cdk1/Cyclin B phosphorylate GEF-H1, thereby inhibiting GEF-H1 catalytic activity.	SIGNOR-276062
P23771	Q9UBL3	binding	up-regulates	0.25	We identifiedgata3as the binding protein of ash2l. Ash2l was shown to potentiate the transcriptional activity ofgata3.	SIGNOR-205312
P63096	Q9GZQ6	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-256708
P35869	P49841	phosphorylation	up-regulates activity	0.25	A proposed model of GSK3β role on AHR function and degradation. AHR is phosphorylated by GSK3β in a p23-dependent manner in HeLa cells. This phosphorylation is required for optimal activation of the ligand-dependent AHR target gene transcription. After phosphorylation, AHR is K63-ubiquitinated and is targeted for the LC3-mediated selective autophagy. When the p23 content is compromised in HeLa cells, AHR is more prone to degradation via autophagy, bypassing the GSK3β phosphorylation of AHR.	SIGNOR-276664
O95837	P25021	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-257424
P08581	Q04206	transcriptional regulation	up-regulates quantity	0.25	Together, these results indicate that the Met gene is a direct target of NFkappaB and that Met participates in NFkappaB-mediated cell survival.	SIGNOR-241929
O95837	P49683	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-257198
P19086	Q9HBW0	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-257324
Q14344	O43614	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-257350
P19086	P28222	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-257115
P19086	Q9NQS5	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-257099
P09471	P47211	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-256966
O95600	Q13351	transcriptional regulation	up-regulates quantity by expression	0.25	Here we report that Klf8 is repressed by Klf3 in vivo and is up-regulated by Klf1. Transcript analysis indicates that Klf8 has two promoters, both containing multiple CACCC elements. Transactivation assays and chromatin immunoprecipitation experiments indicate that Klf3 represses Klf8 directly and that Klf1 activates Klf8 directly.	SIGNOR-266050
P19086	P28336	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-257315
P19086	Q5NUL3	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-257313

Q13332

P98160

0

binding

up-regulates

0.253

We demonstrate here that cptpsigma is a heparin-binding protein and that its basal lamina ligands include the heparan sulfate proteoglycans (hspgs) agrin and collagen xviii.

SIGNOR-115246

P19086

P08912

0

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-257125

Q99704

O14920

0

phosphorylation

up-regulates

0.253

Ikkbeta phosphorylates dok1 s(439)s(443) and s(446)s(450) after tnf-alpha, il-1, or gamma-radiation. mutant dok1 a(439), a(443), a(446), and a(450) differed from wild-type dok1 in not inhibiting platelet-derived growth factor-induced extracellular signal-regulated kinase 1/2 phosphorylation or cell growth. Mutant dok1 a(439), a(443), a(446), and a(450) also did not promote cell motility whereas wild-type dok1 promoted cell motility.

SIGNOR-131447

Q9UQD0

Q92914

0

binding

down-regulates activity

0.253

Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.

SIGNOR-253414

P30305

Q15418

0

phosphorylation

up-regulates

0.253

Rsk promotes g2/m transition through activating phosphorylation of cdc25a and cdc25b rsk is likely to be more active in mitotic cells than in interphase cells, as evidenced by the phosphorylation status of t359/s363 in rsk. Together, these findings indicate that rsk promotes g2/m transition in mammalian cells through activating phosphorylation of cdc25a and cdc25b.

SIGNOR-202125

P35968

P23470

0

dephosphorylation

down-regulates activity

0.253

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254707

P09471

O43614

0

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

P19086

P28566

0

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-257100

P36776

P31749

0

phosphorylation

up-regulates activity

0.253

In mitochondria, LonP1 is phosphorylated by Akt on Ser173 and Ser181, enhancing its protease activity.

SIGNOR-265724

Q09472

Q9UK32

0

phosphorylation

down-regulates activity

0.253

Figure 2G shows that Ser89 phosphorylation of p300, an event that inhibits p300’s acetyltransferase activity (13), was decreased in RSK4-silenced A549 and T24 cells. Consequently, RSK4 may regulate the activity of the NFκB pathway by direct phosphorylation of p300, as recombinant RSK4 phosphorylates p300 on Ser89 in vitro

SIGNOR-275796

P43405

P00519

0

phosphorylation

up-regulates activity

0.253

Abl kinases modulate Syk kinase activation.|Expression of constitutively active Abl (AblPP) increased Syk Y346 phosphorylation, whereas the phosphorylation was unaffected in cells expressing kinase inactive form of Abl (AblKR) (XREF_FIG).

SIGNOR-279665

P09471

Q13639

0

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-257242

Q96LC9

P28482

0

phosphorylation

up-regulates

0.253

Phosphomimetic mutation of this site (s74d) moderately enhanced bmf apoptotic activity in vivo.22 here, we demonstrate a previously unrecognized mode of regulation of bmf. We show that b-raf-mek-erk2 signaling regulates bmf phosphorylation at serine 74 and serine 77. Phosphorylation of serine 77 downregulates the pro-apoptotic activity of bmf.

SIGNOR-195475

Q9H1B7

Q12947

0

transcriptional regulation

up-regulates quantity by expression

0.253

FOXF2 directly bound the promoter of E3 ligase interferon regulatory factor 2-binding protein-like (IRF2BPL) and induced its transcriptional expression. IRF2BPL in turn interacted with β-catenin, increasing its ubiquitination and degradation.

SIGNOR-267152

Q9UK80

Q16539

0

phosphorylation

up-regulates activity

0.253

In this study, we found that USP21 is an important deubiquitinating enzyme for STING and that it negatively regulates the DNA virus-induced production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STING. HSV-1 infection recruited USP21 to STING at late stage by p38-mediated phosphorylation of USP21 at Ser538. I

SIGNOR-273670

Q9HC35

Q9HC98

0

phosphorylation

up-regulates activity

0.253

The mitotic kinases NEK6 and NEK7 phosphorylated the EML4 N-terminal domain at Ser144 and Ser146 in vitro, and depletion of these kinases in cells led to increased EML4 binding to microtubules in mitosis. An S144A-S146A double mutant not only bound inappropriately to mitotic microtubules but also increased their stability and interfered with chromosome congression. In addition, constitutive activation of NEK6 or NEK7 reduced the association of EML4 with interphase microtubules. Together, these data support a model in which NEK6- and NEK7-dependent phosphorylation promotes the dissociation of EML4 from microtubules in mitosis in a manner that is required for efficient chromosome congression.

SIGNOR-273883

Q14847

P12931

0

phosphorylation

up-regulates activity

0.253

Integrin-dependent translocation of LASP-1 to the cytoskeleton of activated platelets correlates with LASP-1 phosphorylation at tyrosine 171 by Src-kinase

SIGNOR-271706

Q99683

Q9H2G2

0

phosphorylation

up-regulates

0.253

Induction of apoptosis by the ste20-like kinase slk, a germinal center kinase that activates apoptosis signal-regulating kinase and p38

SIGNOR-142665

P19086

P21554

0

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-257119

P69905

P09601

0

null

down-regulates activity

0.253

Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regulates cellular hemoprotein, hemoglobin, and heme

SIGNOR-251813

P17252

Q6ZVD8

0

dephosphorylation

down-regulates quantity

0.253

In addition, knockdown of PHLPP expression reduces the rate of phorbol ester-triggered dephosphorylation of the hydrophobic motif, but not turn motif, of PKC alpha

SIGNOR-237051

P05198

Q9Y6E2

0

binding

up-regulates activity

0.253

BZW2, as an evolutionary highly conserved protein, interacts with eIF2 and eIF3 and promotes ternary complex formation in vitro

SIGNOR-261220

P36639

Q13309

0

binding

down-regulates quantity by destabilization

0.253

Here, we report that MTH1 is regulated by polyubiquitination mediated by the E3 ligase Skp2. In melanoma cells, MTH1 was upregulated commonly mainly due to its improved stability caused by K63-linked polyubiquitination. Although Skp2 along with other components of the Skp1-Cullin-F-box (SCF) ubiquitin ligase complex was physically associated with MTH1, blocking the SCF function ablated MTH1 ubiquitination and expression. Conversely, overexpressing Skp2-elevated levels of MTH1 associated with an increase in its K63-linked ubiquitination.

SIGNOR-272790

P98177

Q99576

0

relocalization

down-regulates activity

0.253

GILZ inhibits FOXO1, FOXO3, and FOXO4 transcriptional activities measured with natural or synthetic FOXO-responsive promoters in HL-60 cells.

SIGNOR-256148

P35499

Q92913

0

binding

down-regulates activity

0.252

Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.

SIGNOR-253431

P09471

P50406

0

binding

up-regulates activity

0.252

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-257186

P19086

P32245

0

binding

up-regulates activity

0.252

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-257270

P48775

P43694

0

transcriptional regulation

down-regulates quantity by repression

0.252

GATA4 inhibits expression of the tryptophan oxygenase gene by binding to the TATA box in fetal hepatocytes.

SIGNOR-268994

Q08499

P27361

0

phosphorylation

down-regulates

0.252

These straddle the target residue, ser(579), for erk2 phosphorylation of pde4d3. Mutation of either or both of these docking sites prevented erk2 from being co-immunoprecipitated with pde4d3, ablated the ability of epidermal growth factor to inhibit pde4d3 through erk2 action in transfected cos cells, and attenuated the ability of erk2 to phosphorylate pde4d3 in vitro.

SIGNOR-77578

Q14694

Q13315

0

phosphorylation

up-regulates quantity by stabilization

0.252

The translocation and stabilization of USP10 is regulated by ATM -mediated phosphorylation of USP10 at Thr42 and Ser337.

SIGNOR-276276

O96013

O94806

0

phosphorylation

up-regulates activity

0.252

PAK4 activity is regulated by an autoinhibitory domain that is released upon RhoGTPase binding as well as phosphorylation at Ser474 in the activation loop of the kinase domain. In the present study, we add another level of complexity to PAK4 regulation by showing that phosphorylation at Ser99 is required for its targeting to the leading edge. This phosphorylation is mediated by PKD1 (protein kinase D1)

SIGNOR-275931

P53350

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.252

As indicated in xref , all three Plk1 fragments were ubiquitinated by CHIP, suggesting that CHIP targets multiple sites of Plk1 for ubiquitination.|Mechanistically, CHIP mediated degradation of AR and Plk1 leads to enhanced efficacy of HSP90 inhibitors.

SIGNOR-278532

O94768

Q15139

0

phosphorylation

up-regulates activity

0.252

Coexpression of DRAK2 and a constitutively active PKD mutant (CA-PKD1; PKD1-S738/742E) were sufficient to greatly enhance DRAK2 autophosphorylation, supporting the hypothesis that PKD catalytic activity promotes DRAK2 function.|We note that PKD was able to phosphorylate DRAK2 outside of its C terminus, suggesting that PKD mediated phosphorylation occurs on a site in the 1-290 fragment of DRAK2.

SIGNOR-279753

Q99250

Q92914

0

binding

down-regulates activity

0.252

Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.

SIGNOR-253430

Q14315

Q4L180

0

binding

down-regulates quantity by destabilization

0.252

We identified the extended basophilic phosphosite motif RxRxxp[S/T]xxp[S/T] in various proteins including filamin-C (FLNc). Importantly, this extended motif, located in a unique insert in Ig-like domain 20 of FLNc, is doubly phosphorylated. The protein kinases responsible for this dual-site phosphorylation are Akt and PKCα. Proximity proteomics and interaction analysis identified filamin A-interacting protein 1 (FILIP1) as direct FLNc binding partner. FILIP1 binding induces filamin degradation, thereby negatively regulating its function. Here, dual-site phosphorylation of FLNc not only reduces FILIP1 binding, providing a mechanism to shield FLNc from FILIP1-mediated degradation, but also enables fast dynamics of FLNc necessary for its function as signaling adaptor in cross-striated muscle cells.

SIGNOR-262618

P14416

P41732

0

binding

down-regulates quantity

0.252

Tetraspanin-7 (TSPAN7) is expressed to variable degrees in different tissues, with the highest level in the brain, and multiple mutations in TSPAN7 have been implicated in intellectual disability. Our results showed that TSPAN7 was associated with DRD2 and reduced its surface expression by enhancing DRD2 internalization.Finally, TSPAN7 negatively affects DRD2-mediated signaling.

SIGNOR-265557

P42224

O00141

0

phosphorylation

up-regulates activity

0.252

Notably, A\u03b2-activated SGK1 or JAK2 kinase phosphorylates STAT1 and induces its association with Tau(1\u2013368).

SIGNOR-279281

Q9UHA4

P85298

0

binding

up-regulates activity

0.252

Furthermore, we identify that BPGAP1 (a BCH domain-containing, Cdc42GAP-like Rho GTPase-activating protein) promotes MEK partner 1 (MP1)-induced ERK activation on late endosome through scaffolding MP1/MEK1 complex. This regulatory function requires phosphorylation of BPGAP1 by JNK at its C terminal tail (Ser424) to unlock its autoinhibitory conformation.

SIGNOR-275551

O96013

Q15139

0

phosphorylation

up-regulates activity

0.252

When PKD3 was knocked-down using isoform-specific shRNA (PKD3-shRNA), PAK4 activity (judged by its phosphorylation status at the activation loop using the pS474-PAK4 antibody) was decreased

SIGNOR-275930

P35354

P11831

0

null

up-regulates

0.252

Srf within myofibers modulates Il6 and Cox2/Il4 expressions and, therefore, exerts a paracrine control of satellite cell proliferation and fusion, respectively, which in turn support skeletal muscle hypertrophy.

SIGNOR-255965

Q8TCU6

Q8WXX7

0

binding

up-regulates activity

0.252

Mutations in the Autism susceptibility candidate 2 gene (AUTS2), whose protein is believed to act in neuronal cell nuclei, have been associated with multiple psychiatric illnesses, including autism spectrum disorders, intellectual disability, and schizophrenia. Here we show that cytoplasmic AUTS2 is involved in the regulation of the cytoskeleton and neural development. AUTS2 activates Rac1 to induce lamellipodia but downregulates Cdc42 to suppress filopodia. Our loss-of-function and rescue experiments show that a cytoplasmic AUTS2-Rac1 pathway is involved in cortical neuronal migration and neuritogenesis in the developing brain. These results suggest that FL-AUTS2 can activate Rac1 via interaction with P-Rex1 and the Elmo2/Dock180 complex to regulate actin dynamics in N1E-115 cells.

SIGNOR-266817

Q9Y2I6

Q96GD4

0

phosphorylation

up-regulates

0.252

Importantly, nlp is characterized as a novel substrate of aurora b and can be phosphorylated by aurora b. The specific phosphorylation sites are mapped at ser-185, ser-448, and ser-585. The phosphorylation at ser-448 and ser-585 is likely required for nlp association with aurora b and localization at midbody. Meanwhile, the phosphorylation at ser-185 is vital to nlp protein stability. Disruptions of these phosphorylation sites abolish cytokinesis and lead to chromosomal instability.

SIGNOR-168053

P19086

Q9Y5X5

0

binding

up-regulates activity

0.252

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-257104

P17947

O15550

0

transcriptional regulation

down-regulates quantity by repression

0.252

Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase

SIGNOR-260036

Q9NZ72

P49840

0

phosphorylation

up-regulates activity

0.252

Altogether, these results indicate that CDK5 phosphorylates similarly serines 68 and 73, whereas ERK2 targets mostly serine 68 and GSK-3beta mostly serine 60.|This observation may support the hypothesis of a specific localization of stathmin 3 depending on its phosphorylation by GSK-3beta

SIGNOR-264883

P04271

O43248

0

transcriptional regulation

up-regulates quantity by expression

0.252

HOXC6 and HOXC11 increase transcription of S100beta gene in BrdU-induced in vitro differentiation of GOTO neuroblastoma cells into Schwannian cells.

SIGNOR-261647

P38936

Q92945

0

post transcriptional regulation

down-regulates quantity by destabilization

0.252

Importantly, KSRP knockdown in C2C12 GM cells (Figure 2D) stabilized endogenous my- ogenin and p21 transcripts (Figure 2E). Furthermore, stable knockdown of KSRP, using shRNA, induced the accumulation of p21 mRNA in C2C12 GM while it did not affect the expression of late myogenic markers (MHC and muscle-creatine kinase [MCK])

SIGNOR-235859

P63096

P32238

0

binding

up-regulates activity

0.252

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-257035

P61006

O43318

0

phosphorylation

up-regulates activity

0.252

In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. |Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease

SIGNOR-260266

P07101

Q99742

0

transcriptional regulation

down-regulates quantity by repression

0.252

Overexpression and siRNA experiments revealed that NPAS1, in concert with ARNT, negatively regulates the expression of TH and that this regulation is mediated by a direct binding of NPAS1 on the TH promoter.

SIGNOR-253702

P08754

P32238

0

binding

up-regulates activity

0.252

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-257148

Q9UNS1

P04150

0

transcriptional regulation

up-regulates quantity by expression

0.252

GR directly regulates transcription of circadian clock components in mouse and human primary MSCs. Per2, E4bp4, Per1, and Timeless rapidly respond to glucocorticoid stimulation. Primary glucocorticoid receptor (GR) target genes are those at which GR occupies a nearby genomic glucocorticoid response element (GRE) and regulates target gene transcription

SIGNOR-268052

P19086

Q9GZQ6

0

binding

up-regulates activity

0.252

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-257103

P35372

P04843

0

binding

up-regulates

0.252

Ribophorin i (rpni), a component of the oligosaccharide transferase complex, could directly interact with mor. Rpni can be shown to participate in mor export by the intracellular retention of the receptor after small interfering rna knockdown of endogenous rpni.

SIGNOR-184651

P09471

P32238

0

binding

up-regulates activity

0.252

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-257236

P68363

Q5SQI0

0

acetylation

up-regulates quantity by stabilization

0.252

Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules

SIGNOR-272245

P19086

P41146

0

binding

up-regulates activity

0.252

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-257117

P55075

P40425

0

transcriptional regulation

down-regulates quantity by repression

0.251

Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription

SIGNOR-265778

P52565

Q9ULL4

0

binding

up-regulates activity

0.251

Here, we report the expression of plexin-B3 in glioma cells, which upon stimulation by its ligand Sema5A results in significant inhibition of cell migration and invasion. A search for the underlying mechanism revealed direct interaction of plexin-B3 with RhoGDP dissociation inhibitor α (RhoGDIα), a negative regulator of RhoGTPases that blocks guanine nucleotide exchange and sequesters them away from the plasma membrane. direct interaction of RhoGDIα and the cytoplasmic domain of plexin-B3 (plexin-B3CD) was confirmed by GST pulldown assays.

SIGNOR-268435

P45973

Q9C0F0

0

binding

down-regulates activity

0.251

Here, we showed that ASXL3 interacts with HP1α and LSD1, leading to transcriptional repression.

SIGNOR-266763

P23588

Q14004

0

phosphorylation

up-regulates activity

0.251

CDK13 directly phosphorylates 4E-BP1 at Thr46 and eIF4B at Ser422; genetically or pharmacologically inhibiting CDK13 disrupts mRNA translation.

SIGNOR-273115

Q9HAW8

P20823

0

transcriptional regulation

up-regulates quantity by expression

0.251

Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter.

SIGNOR-253971

Q9NPD5

P20823

0

transcriptional regulation

up-regulates quantity by expression

0.251

Farnesoid X receptor, hepatocyte nuclear factors 1alpha and 3beta are essential for transcriptional activation of the liver-specific organic anion transporter-2 gene.|This study demonstrated that the transcription of the LST-2 gene is regulated by three transcription factors, FXR, HNF1alpha, and HNF3beta.

SIGNOR-268988

O95817

Q05655

0

phosphorylation

up-regulates

0.251

Pkc_-mediated phosphorylation of bag3 at ser187 site induces epithelial-mesenchymal transition and enhances invasiveness in thyroid cancer fro cells. we showed that bag3 was implicated in epithelial-mesenchymal transition (emt) procedure, and phosphorylation state at ser187 site had a critical role in emt regulation by bag3.

SIGNOR-199316

P31941

Q13617

0

ubiquitination

down-regulates quantity by destabilization

0.251

Human Papillomavirus 16 E7 Stabilizes APOBEC3A Protein by Inhibiting Cullin 2-Dependent Protein Degradation|Here, we report that the HPV oncoprotein E7 stabilizes the APOBEC3A (A3A) protein in human keratinocytes by inhibiting ubiquitin-dependent protein degradation in a cullin-dependent manner.

SIGNOR-261325

Q92997

Q8IZQ1

0

relocalization

down-regulates quantity by destabilization

0.251

Our data taken together with the known role of ALFY in autophagy, demonstrate specific targeting and autophagy-mediated removal of DVL3 by hALFY.

SIGNOR-266793

Q76N32

P51955

0

phosphorylation

down-regulates quantity by destabilization

0.251

In this study we show phosphorylation of Cep68 by Nek2 creates a potential phosphodegron that directs Cep68 destruction through the activity of SCF-beta-Trcp.|Our above results showed that Nek2 promoted mitotic degradation of Cep68.

SIGNOR-279471

P48664

P35398

0

transcriptional regulation

up-regulates quantity by expression

0.251

RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.

SIGNOR-266850

P35869

P53350

0

phosphorylation

down-regulates activity

0.251

In this study, we demonstrate that PLK1 phosphorylates AHR at S489 in LUAD, leading to epithelial-mesenchymal transition (EMT) and metastatic events.

SIGNOR-277885

Q15465

P35398

0

transcriptional regulation

up-regulates quantity by expression

0.251

RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.

SIGNOR-266846

P49716

Q9P2J3

0

binding

down-regulates quantity by destabilization

0.251

KLHL9 mediates poly-ubiquitylation of C/EBPβ and C/EBPδ isoforms. We confirmed KLHL9 deletions in an independent cohort and showed that this protein is necessary for Cul3-ligase mediated ubiquitylation and proteasomal degradation of established MES-GBM MRs, C/EBPβ and C/EBPδ.

SIGNOR-272459

P35247

P17676

0

transcriptional regulation

up-regulates quantity by expression

0.251

Cotransfection of C/EBPalpha, C/EBPbeta, or C/EBPdelta cDNA in H441 lung adenocarcinoma cells significantly increased the luciferase activity of a wild-type SP-D promoter construct containing 698 bp of upstream sequence (SS698). Transfection of C/EBP also increased the level of endogenous SP-D mRNA in H441 cells| Thus, interactions among C/EBP elements in the near-distal promoter can modulate the promoter activity of SP-D.

SIGNOR-254045

P05198

Q92879

0

binding

up-regulates activity

0.251

These studies showed that both the increased levels of CUGBP1 and cdk4-mediated hyper-phosphorylation of CUGBP1 are involved in the age-associated induction of the CUGBP1-eIF2 complex. The CUGBP1-eIF2 complex is bound to C/EBPbeta mRNA in the liver of old animals, and this binding correlates with the increased amounts of liver-enriched activator protein and liver-enriched inhibitory protein.

SIGNOR-262736

P40763

O43683

0

phosphorylation

up-regulates activity

0.251

This study showed that the BUB1 kinase drives the progression and proliferation of BCa by regulating the transcriptional activation of STAT3 signaling and may be an attractive candidate for therapeutic targeting in BCa.|We further identified through a series of molecular and cell biological approaches that BUB1 interacted directly with STAT3 and mediated the phosphorylation of STAT3 at Ser727.

SIGNOR-280198

Q9Y625

O95644

0

transcriptional regulation

up-regulates quantity by expression

0.251

NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype.

SIGNOR-264022

P55085

Q15661

0

binding

up-regulates activity

0.251

Mast cells contribute to tissue repair in fibrous tissues by stimulating proliferation of fibroblasts through the release of tryptase which activates protease-activated receptor-2 (PAR-2).|Taken together, our data show that tryptase can stimulate myoblast proliferation and this effect is part of a signaling cascade dependent on PAR-2 activation and on the downstream activation of COX-2.

SIGNOR-251744

Q05397

P16591

0

phosphorylation

up-regulates activity

0.251

The Fer mediated phosphorylation of specific tyrosine residues of FAK was abolished by cotransfection of shRNA against Fer (i.e., shFer), but not by control shRNA, indicating that the phosphorylation of Tyr577, 861, or 925 of FAK in suspended cells was indeed caused by Fer.

SIGNOR-279409

O95433

P00519

0

phosphorylation

up-regulates activity

0.251

Here, we show that c-Abl kinase phosphorylates Y223 in human Aha1 (hAha1), promoting its interaction with Hsp90. This, consequently, results in an increased Hsp90 ATPase activity

SIGNOR-260938

P03372

Q9Y5X4

0

transcriptional regulation

up-regulates quantity by expression

0.251

NR2E3 directly regulates expression of ESR1 | Furthermore, overexpression of exogenous NR2E3 further increased expression of ESR1 and its downstream targets as well as its transcriptional activity in MCF-7 cells (Fig S1 of Supporting Information), strongly demonstrating that NR2E3 regulates ESR1 expression and subsequent ESR1-mediated induction of target genes.

SIGNOR-266207

P10451

P15036

0

transcriptional regulation

up-regulates quantity by expression

0.251

We demonstrated that Ets2 is capable of binding to and transactivating the OPN promoter using gel shift and transient transfection assays

SIGNOR-259872

Q15031

P18848

0

transcriptional regulation

up-regulates quantity by expression

0.251

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269421

O60716

P17252

0

phosphorylation

down-regulates activity

0.251

PKC\u03b1 phosphorylation of p120 at S879 is a critical phospho-switch mediating disassociation of p120 from VE-cadherin that results in AJ disassembly.|We surmised that PKCalpha may function to disrupt AJs by signaling dissociation of p120 from VE-cadherin.

SIGNOR-278261

Q14344

P30989

0

binding

up-regulates activity

0.25

Altogether, these results reveal for the first time the ability of hNTS1 to directly activate the Gαq-, Gαi1-, GαoA-, and Gα13-mediated signaling pathways

SIGNOR-278060

P19484

Q8IVH8

0

phosphorylation

down-regulates activity

0.25

However, although our results indicate that MAP4K3 initiates TFEB repression, MAP4K3 also promotes robust mTORC1 activation upon amino acid stimulation - ; hence, MAP4K3 and mTORC1 must ultimately work together to achieve robust suppression of autophagy.|Moreover, MAP4K3 serine 3 phosphorylation of TFEB is required for TFEB interaction with mTORC1-Rag GTPase-Ragulator complex and TFEB cytosolic sequestration.

SIGNOR-278282

P50148

Q13639

0

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-257367

Q92974

Q96GD4

0

phosphorylation

down-regulates activity

0.25

The mitotic kinases Aurora A/B and Cdk1/Cyclin B phosphorylate GEF-H1, thereby inhibiting GEF-H1 catalytic activity.

SIGNOR-276062

P23771

Q9UBL3

0

binding

up-regulates

0.25

We identifiedgata3as the binding protein of ash2l. Ash2l was shown to potentiate the transcriptional activity ofgata3.

SIGNOR-205312

P63096

Q9GZQ6

0

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-256708

P35869

P49841

0

phosphorylation

up-regulates activity

0.25

A proposed model of GSK3β role on AHR function and degradation. AHR is phosphorylated by GSK3β in a p23-dependent manner in HeLa cells. This phosphorylation is required for optimal activation of the ligand-dependent AHR target gene transcription. After phosphorylation, AHR is K63-ubiquitinated and is targeted for the LC3-mediated selective autophagy. When the p23 content is compromised in HeLa cells, AHR is more prone to degradation via autophagy, bypassing the GSK3β phosphorylation of AHR.

SIGNOR-276664

O95837

P25021

0

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-257424

P08581

Q04206

0

transcriptional regulation

up-regulates quantity

0.25

Together, these results indicate that the Met gene is a direct target of NFkappaB and that Met participates in NFkappaB-mediated cell survival.

SIGNOR-241929

O95837

P49683

0

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-257198

P19086

Q9HBW0

0

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-257324

Q14344

O43614

0

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-257350

P19086

P28222

0

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-257115

P19086

Q9NQS5

0

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-257099

P09471

P47211

0

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-256966

O95600

Q13351

0

transcriptional regulation

up-regulates quantity by expression

0.25

Here we report that Klf8 is repressed by Klf3 in vivo and is up-regulated by Klf1. Transcript analysis indicates that Klf8 has two promoters, both containing multiple CACCC elements. Transactivation assays and chromatin immunoprecipitation experiments indicate that Klf3 represses Klf8 directly and that Klf1 activates Klf8 directly.

SIGNOR-266050

P19086

P28336

0

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-257315

P19086

Q5NUL3

0

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-257313