GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q16543	P19784	0	phosphorylation	up-regulates activity	0.489	Phosphorylation of serine 13 is required for the proper function of the Hsp90 co-chaperone, Cdc37. \| In this report, we demonstrate that mammalian Cdc37 is phosphorylated on Ser13 in situ in rabbit reticulocyte lysate and in cultured K562 cells and that casein kinase II is capable of quantitatively phosphorylating recombinant Cdc37 at this site.	SIGNOR-250982
O95837	P35348	2	binding	up-regulates activity	0.435	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257195
Q13153	O14950	1	phosphorylation	up-regulates activity	0.484	It has been shown that PAK1 phosphorylates and activates MLC2, leading to cell motility [ xref ].	SIGNOR-280053
P41597	P13500	2	binding	up-regulates activity	0.786	The investigators showed that myoblasts constitutively express receptors for CCL2 (CCR2), CCL3 (CCR1 and CCR5), and CCL4 (CCR5), and that stimulation with either CCL2 or CCL4 was sufficient to promote myoblast proliferation.	SIGNOR-255113
Q13542	P42345	0	phosphorylation	down-regulates	0.661	Here, we show that cancer cells acquire resistance to astori by downregulating eukaryotic translation initiation factor (eif4e)-binding proteins (4e-bps-eif4ebp1, eif4ebp2).	SIGNOR-122014
P17612	P52565	1	phosphorylation	down-regulates	0.387	The results indicate that phosphorylation of gdi_ at ser174 by pka suppresses rhoa activity, providing a potential protective signaling mechanism for inflammatory injury.	SIGNOR-180576
P23759	Q03164	2	binding	up-regulates	0.2	Carm1 specifically methylates multiple arginines in the n-terminus of pax7. Methylated pax7 directly binds the c-terminal cleavage forms of the trithorax proteins mll1/2 resulting in the recruitment of the ash2l:mll1/2:wdr5:rbbp5 histone h3k4 methyltransferase complex to regulatory enhancers and the proximal promoter of myf5.	SIGNOR-198626
Q9C0B5	P06241	0	phosphorylation	up-regulates quantity by stabilization	0.388	Our study demonstrates that under basal conditions, PSD-95 and Fyn cooperatively stabilize DHHC5 at the synaptic membrane through Fyn-mediated phosphorylation of DHHC5 at tyrosine residue 533 and the subsequent inhibition of DHHC5 association with endocytic proteins (Fig. 10).	SIGNOR-279738
P53350	P12830	1	phosphorylation	down-regulates quantity by destabilization	0.297	Priming phosphorylation of Cdh1 by the Cdk2/cyclin A kinase complex allows Plk1 to bind to Cdh1 and phosphorylate Cdh1 at Ser138 and Ser146. Phosphorylation of Cdh1 at Ser138 and Ser146 then triggers its interaction with, and subsequent ubiquitination by, SCFbeta-TRCP	SIGNOR-274054
P37840	P43405	0	phosphorylation	down-regulates	0.532	Here, we show that alpha-synuclein (alpha-syn) is an outstanding substrate for the protein tyrosine kinase p72syk (syk), which phosphorylates three tyrosyl residues in its c-terminal domain (y-125, y-133, and y-136), here, we show that _-syn is an outstanding substrate for syk and that once it is tyrosine phosphorylated, it loses the ability to form oligomers.	SIGNOR-113065
P15941	O43474	2	binding	up-regulates activity	0.281	Previous work has shown that the Kruppel-like factor 4 (KLF4) transcription factor represses p53 transcription by binding to the PE21 element. Our results show that MUC1-C binds constitutively to KLF4, occupies PE21 with KLF4, and enhances the KLF4 occupancy of PE21.	SIGNOR-270543
P01308	P08069	2	binding	up-regulates	0.89	Because of the sequence homology and tertiary structure similarities between proinsulin (pi) and insulin-like growth factor-i (igf-i), it is possible that pi interacts with the igf-i receptor with higher affinity than insulin.	SIGNOR-22083
Q9GZM8	P60510	0	dephosphorylation	down-regulates activity	0.395	Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation\|PP4c selectively dephosphorylates NDEL1 at Cdk1 sites. We also demonstrate that PP4c negatively regulates Cdk1 activity at the centrosome.\|We next examined the ability of PP4c to dephosphorylate a Cdk1 phosphorylation site, phospho-T219	SIGNOR-248550
P01111	Q07889	0	guanine nucleotide exchange factor	up-regulates activity	0.78	Sos and Ras-GRF are two families of guanine nucleotide exchange factors that activate Ras proteins in cells. Sos proteins are ubiquitously expressed and are activated in response to cell-surface tyrosine kinase stimulation Sos1 and Ras-GRF1 activate the Ras proteins Ha-Ras, N-Ras, and Ki-Ras	SIGNOR-110566
P31749	P48431	1	phosphorylation	up-regulates quantity by stabilization	0.532	In contrast, phosphorylation of Sox2 by AKT1 at T118 blocks K119me by Set7 and stabilizes Sox2.	SIGNOR-279003
Q13469	P19883	1	transcriptional regulation	up-regulates quantity by expression	0.2	MyoD, CREB, and NFAT Mediate the Transcriptional Activation of the Follistatin Promoter Induced by TSA	SIGNOR-251729
Q9NRC8	P22087	1	deacetylation	up-regulates activity	0.271	Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7.\|hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromising H2AQ104 methylation (H2AQ104me) and rDNA transcription. SIRT7-dependent deacetylation of FBL ensures H2AQ104me and high levels of rRNA synthesis during interphase. \|Global acetylome studies have shown that FBL is acetylated at four conserved lysine residues (K102, K121, K205, and K206)	SIGNOR-275894
Q9UHC6	Q6ZVD7	0	transcriptional regulation	down-regulates quantity by repression	0.2	In this study we performed chromatin immunoprecipitation coupled to shotgun cloning to discover novel STOX1A target genes. Our results show that CNTNAP2, a member of the neurexin family, is directly downregulated by STOX1A.	SIGNOR-269065
Q9NVD7	P28482	0	phosphorylation	up-regulates activity	0.259	Actopaxin (alpha-parvin) is a paxillin, integrin-linked kinase, and F-actin binding focal adhesion protein with several serine phosphorylation sites in the amino terminus that contribute to the regulation of cell spreading and migration.\|Actopaxin phosphorylation of Ser4/8 enhances cell migration whereas a nonphosphorylatable (Quint) mutant suppresses migration in U2OS osteosarcoma cells (7).	SIGNOR-265759
P10589	P22888	1	transcriptional regulation	down-regulates quantity by repression	0.275	Functional analysis showed that EAR2 and EAR3/COUP-TFI repressed the hLHR promoter activity, whereas TR4 activated hLHR gene transcription.	SIGNOR-266218
O75376	P31749	0	phosphorylation	down-regulates	0.424	Akt-induced phosphorylation of n-cor at serine 1450 contributes to its misfolded conformational dependent loss (mcdl) in acute myeloid leukemia of the m5 subtype.	SIGNOR-198913
P54132	Q8IYW5	0	ubiquitination	up-regulates activity	0.262	Here, we demonstrate that the ubiquitin/SUMO-dependent DNA damage response (UbS-DDR), controlled by the E3 ligases RNF8/RNF168, triggers BLM recruitment to sites of replication fork stalling via ubiquitylation in the N-terminal region of BLM and subsequent BLM binding to the ubiquitin-interacting motifs of RAP80.	SIGNOR-272114
P00533	Q8ND25	1	phosphorylation	up-regulates activity	0.27	Together, these results demonstrate that EGFR-dependent phosphorylation of ZNRF1 at Y103 promotes degradation of AKT and resultant activation of GSK3\u03b2, which mediates oxidative stress\u2013induced neuronal apoptosis ( xref ).	SIGNOR-279522
P04637	Q15759	0	phosphorylation	up-regulates	0.611	We show that prak activates p53 by direct phosphorylation.	SIGNOR-152843
O43586	P50570	2	binding	down-regulates	0.374	We show that pstpip1 associates with the regulator of endocytosis, dynamin 2, and pstpip1 expression impairs transferrin uptake and endocytosis	SIGNOR-178628
Q13200	Q05086	0	ubiquitination	down-regulates quantity by destabilization	0.277	Our experiments collectively suggest that UBE3A stimulates Wnt pathway activation by interacting with, ubiquitinating, and reducing the levels of multiple (PSMB1, PSMC2, PSMD2, and PSMD7) proteasome subunits.	SIGNOR-265133
P50148	P34998	2	binding	up-regulates activity	0.286	Previous studies have indicated that CRHR could couple to multiple Galpha proteins including Gs, Gi, and Gq/11 and then go on to induce changes in AC activity and activation of PLC-beta3	SIGNOR-268619
P78545	Q13153	0	phosphorylation	up-regulates	0.456	Phosphorylation-dependent regulation of stability and transforming potential of ets transcriptional factor ese-1 by p21-activated kinase 1. Pak1 selectively phosphorylates ese-1 at ser(207). Intriguingly, pak1 phosphorylation inactive mutant ese1-s207a is more unstable	SIGNOR-154743
Q9BPV8	P30679	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257143
Q96T88	P24941	0	phosphorylation	down-regulates quantity by destabilization	0.303	UHRF1 is phosphorylated by CDK2/cyclin A. In vitro kinase assay was performed with CDK2/cyclin A using recombinant wild-type UHRF1 or UHRF1-S674A mutant	SIGNOR-277192
Q01543	Q13547	0	deacetylation	up-regulates	0.2	Hdac1 interacts with fli1 and mediates its deacetylation / our previous studies have shown that pcaf-dependent acetylation of fli1 at lysine 380 decreases its protein stability / p300 promotes the interaction of fli1 with hdac1 and increases the dna binding ability of fli1 through deacetylation of lysine 380	SIGNOR-202689
P68400	P18146	1	phosphorylation	down-regulates activity	0.464	Casein kinase II associates with Egr-1 and acts as a negative modulator of its DNA binding and transcription activities in NIH 3T3 cells. \| There are three CKII recognition sites (S376XXD, T389XE, and T516XXXD) in fragment 10.	SIGNOR-250858
O14965	P55072	2	binding	down-regulates activity	0.313	The UBXN-2/p37/p47 adaptors of CDC-48/p97 regulate mitosis by limiting the centrosomal recruitment of Aurora A.\|We found that UBXN-2 and CDC-48 coimmunoprecipitated with AIR-1 from embryonic extracts	SIGNOR-265044
P25098	O95398	1	phosphorylation	down-regulates activity	0.2	The observation that GRK2 co-immunoprecipitates with Epac1 suggests a direct association between GRK2 and Epac1 in DRGs. xref A detailed study of the influence of GRK2 on the Epac1 level found that phosphorylation of ser108 in Epac1 by GRK2 can lead to a reduction of Epac1 activation. xref Downstream consequence of a reduction of GRK2 was explored. xref Low GRK2 expression in GRK2(\u00b1) DRGs was found to facilitate CPT-induced Rap1 activation and increase the phosphorylated ERK1/2 level.	SIGNOR-280001
Q96DX5	P12277	1	polyubiquitination	down-regulates quantity by destabilization	0.683	We demonstrate that creatine kinase B (CKB) interacts with Asb-9 in a specific, SOCS box-independent manner. This interaction increases the polyubiquitylation of CKB and decreases total CKB levels within the cell. The targeting of CKB for degradation by Asb-9 was primarily SOCS box-dependent and suggests that Asb-9 acts as a specific ubiquitin ligase regulating levels of this evolutionarily conserved enzyme.	SIGNOR-271623
P15735	P46019	2	binding	down-regulates activity	0.916	Phk is among the most complex of the protein kinases so far elucidated. It has one catalytic (gamma) subunit and three different regulatory (alpha, beta, and delta) subunits, a molecular mass of 1.3 X 106 daltons, and each holoenzyme molecule is presumed to contain four molecules of each subunit. The three regulatory subunits inhibit the phosphotransferase activity of the gamma subunit.	SIGNOR-267406
Q9UQM7	P29475	1	phosphorylation	down-regulates activity	0.471	It was found that purified recombinant nNOS was phosphorylated by CaM-K Ialpha, CaM-K IIalpha, and CaM-K IV at Ser847 in vitro. Replacement of Ser847 with Ala (S847A) prevented phosphorylation by CaM kinases. Phosphorylated recombinant wild-type nNOS at Ser847 (approximately 0.5 mol of phosphate incorporation into nNOS) exhibited a 30% decrease of Vmax with little change of both the Km for L-arginine and Kact for CaM relative to unphosphorylated enzyme. The activity of mutant S847D was decreased to a level 50-60% as much as the wild-type enzyme. The decreased NOS enzyme activity of phosphorylated nNOS at Ser847 and mutant S847D was partially due to suppression of CaM binding, but not to impairment of dimer formation which is thought to be essential for enzyme activation.	SIGNOR-250635
Q92915	Q8NEV1	0	phosphorylation	up-regulates activity	0.269	Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents.	SIGNOR-275743
Q00653	P20749	2	binding	up-regulates	0.573	The cyclin d1 elevation is caused not by increased p65/p50 action but rather by increased nuclear activity of bcl-3-associated nf-kappab p50 and p52.	SIGNOR-146768
Q8ND76	P06493	0	phosphorylation	down-regulates activity	0.595	Therefore, CDK1 may trigger CFP1 degradation through some indirect mechanisms rather than CFP1 phosphorylation.\|This result suggests that, although CDK1 triggers both phosphorylation and degradation of CFP1 protein, phosphorylation of CFP1 by CDK1 is not a prerequisite for its degradation during cell division.	SIGNOR-279012
P63096	P28335	2	binding	up-regulates activity	0.293	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-256734
Q9HC97	P09471	2	binding	up-regulates activity	0.25	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256996
Q15466	P10275	2	binding	down-regulates	0.415	We demonstrated that shp inhibited both ar-lbd and ntd-dependent transactivation, which evidenced for the first time a protein capable of inhibiting a steroid receptor amino-terminal-dependent transactivation. We further characterized the shp mechanism of action by showing that shp reversed ar coactivator-mediated activation	SIGNOR-112589
P12931	P20701	1	phosphorylation	down-regulates activity	0.421	PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.	SIGNOR-254741
P15172	Q02363	2	binding	down-regulates activity	0.54	Id1 and Id2 interacted strongly with MyoD and Myf-5.Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo.	SIGNOR-240268
P16403	O76064	0	polyubiquitination	down-regulates	0.2	ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2.	SIGNOR-272928
P78527	P50876	0	polyubiquitination	down-regulates quantity by destabilization	0.568	We show that RNF144A induces ubiquitination of DNA-PKcs in vitro and in vivo and promotes its degradation.	SIGNOR-272213
Q6ZNA4	P61956	1	polyubiquitination	down-regulates quantity by destabilization	0.626	Arkadia ubiquitinates poly-SUMO2 chains in a SIM- and RING-dependent manner.	SIGNOR-272882
P52948	P59634	2	binding	down-regulates activity	0.2	Orf6 of SARS-CoV antagonizes host interferon signaling by perturbing nuclear transport, and the NUP98-RAE1 interaction with Orf6 may perform the same function for SARS-CoV-2.	SIGNOR-260976
Q05397	Q05209	0	dephosphorylation	down-regulates activity	0.538	We demonstrate here that activated Ras induces tyrosine dephosphorylation and inhibition of FAK mediated by the Ras downstream Fgd1-Cdc42-PAK1-MEK-ERK signaling cascade.\| PIN1 binding and prolyl isomerization of FAK cause PTP-PEST to interact with and dephosphorylate FAK Y397. Inhibition of FAK mediated by this signal relay promotes Ras-induced cell migration, invasion, and metastasis.	SIGNOR-248661
Q86V86	Q92934	1	phosphorylation	down-regulates activity	0.346	Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. pim kinases are constitutively active when expressed in HEK-293 cells and are able to phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and Ser155 in vitro and in cells.	SIGNOR-250399
P10828	P27361	0	phosphorylation	down-regulates activity	0.428	We concluded that serine 142 of the tr dbd is the likely site of phosphorylation by t(4)-activated mapk and that the docking site on tr for activated mapk includes residues 128-133 (kgffrr), a basic amino acid-enriched motif novel for mapk substrates. Tr mutations in the proposed mapk docking domain and at residue 142 modulated t(4)-conditioned shedding of co-repressor and recruitment of co-activator proteins by the receptor, and they altered transcriptional activity of tr in a thyroid hormone response element-luciferase reporter assay.	SIGNOR-102224
Q99661	Q13153	0	phosphorylation	down-regulates	0.385	Here we found that mcak is a cognate substrate of pak1 wherein pak1 phosphorylates mcak on serines 192 and 111 both in vivo and in vitro. Furthermore, we found that pak1 phosphorylation of mcak on serines 192 and 111 preferentially regulates its microtubule depolymerization activity and localization to centrosomes	SIGNOR-199084
Q96SB3	P17612	0	phosphorylation	down-regulates activity	0.31	Spinophilin is phosphorylated in vitro by protein kinase A (PKA). two major sites of phosphorylation, Ser-94 and Ser-177, that are located within the actin-binding domain of spinophilin. Phosphorylation of spinophilin by PKA modulated the association between spinophilin and the actin cytoskeleton. phosphorylation of spinophilin reduced the stoichiometry of the spinophilin-actin interaction. In contrast, the ability of spinophilin to bind to PP1 remained unchanged.	SIGNOR-250035
Q86TM6	Q16236	1	ubiquitination	down-regulates quantity by destabilization	0.2	NRF2 is negatively regulated by three E3 ubiquitin ligase complexes: the KEAP1-CUL3-RBX1 complex, the β-TrCP-SKP1-CUL1-RBX1 complex, and HRD1.	SIGNOR-267360
P16333	P00533	2	binding	up-regulates activity	0.576	We show that epidermal growth factor or platelet-derived growth factor stimulation of intact human or murine cells leads to phosphorylation of Nck protein on tyrosine, serine, and threonine residues	SIGNOR-252089
Q96SN8	O95613	2	binding	up-regulates activity	0.819	Our observation that Cep215 may function downstream of pericentrin suggests that the two proteins affect centrosome cohesion through a common mechanism. \|Finally, depletion of pericentrin caused an almost complete loss of Cep215 from centrosomes, a detectable reduction in centrosomal levels of Cep68 and rootletin, but no significant effect on C-Nap1 (Fig. 6C and Table 1). Taken together, these results point to functional (and perhaps molecular) interactions between (1) Cep68 and rootletin and (2) Cep215 and pericentrin.	SIGNOR-260309
P13501	P51681	2	binding	up-regulates activity	0.937	CCL5, also known RANTES (regulated on activation, normal T cell expressed and secreted), is a potent chemoattractant for a variety of leukocytes, including T cells, mono- cytes, NK cells, and basophils, signaling via the CCR1, CCR3, and CCR5 cell surface receptors [59]. Among these receptors, CCL5 has the highest affinity for CCR5.	SIGNOR-277726
P27361	P48431	1	phosphorylation	down-regulates activity	0.452	Mass spectrum analysis was employed after an in vitro kinase assay in which cells were incubated with or without ERK1-active kinase, and the results demonstrated that Sox2 was phosphorylated by ERK1 directly at S251, which was further verified by western blotting for the specific antibody targeting S251 phosphorylated Sox2 after the in vitro kinase assay.\|Mechanistically, ERK1 kinase promoted autophagic degradation of Sox2 via phosphorylation of Sox2 at Ser251 and further SUMOylation of Sox2 at Lys245 in non CSCs.	SIGNOR-279071
P36941	Q12933	2	binding	up-regulates activity	0.586	Endogenous association of traf2, traf3, ciap1, and smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis.	SIGNOR-97950
Q5S007	Q96CW1	1	phosphorylation	up-regulates activity	0.259	These data confirmed that LRRK2 phosphorylates AP2M1 at Thr 156 in vitro.	SIGNOR-278183
Q12778	P30304	0	dephosphorylation	up-regulates activity	0.313	In this study, we revealed that Cdc25A enhances Foxo1 stability by dephosphorylating Cdk2, and Foxo1 was shown to directly regulate transcription of the metastatic factor MMP1.	SIGNOR-277139
P63096	Q96P68	2	binding	up-regulates activity	0.385	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-257042
P45983	Q13526	1	phosphorylation	up-regulates quantity by stabilization	0.272	Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation.	SIGNOR-277562
P35900	P49137	0	phosphorylation	up-regulates activity	0.2	P38 phosphorylates the type II keratin, K8 at Ser73, whereas MK2 phosphorylates the binding partners K18 at Ser52 and K20 at Ser13.	SIGNOR-263071
Q9NQL2	Q8NFG4	0	gtpase-activating protein	up-regulates activity	0.683	The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1 [..} RagC/D is a key regulator of the interaction of mTORC1 with the Rag heterodimer and that, unexpectedly, RagC/D must be GDP-bound for the interaction to occur	SIGNOR-256504
P20309	O95837	2	binding	up-regulates activity	0.411	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-257134
P42574	Q4V328	1	cleavage	up-regulates activity	0.414	These results suggest that the region of GRASP‐1 downstream of the Caspase‐3‐cleavage site is capable of activating the JNK signaling pathway by enhancing the phosphorylation of JNK. these results suggest that full length GRASP‐1 does not enhance JNK pathway activity, possibly due to the inhibitory effect of the N‐terminal fragment on the C‐terminal fragment. In contrast, Caspase‐3 cleavage of GRASP‐1 releases the C‐terminal fragment, which in turn activates JNK signaling by serving as a scaffold protein.	SIGNOR-260641
P40763	Q14289	0	phosphorylation	up-regulates activity	0.428	These results imply that following EGF stimulation, PYK2 enhances a STAT3-dependent IL8 expression, thus creating a positive feedback loop between ErbB receptors, PYK2, and IL8.\|These results suggest that PYK2-induced STAT3 phosphorylation is crucial for IL8 secretion, while IL8 is crucial for EGF-induced MMP9 transcription (Figure xref ) and for SKBR3 invasion (Figure xref ).	SIGNOR-279429
Q96DT5	Q92949	0	transcriptional regulation	up-regulates quantity by expression	0.361	FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).	SIGNOR-266931
P31948	P08238	2	binding	down-regulates activity	0.855	Hsp90 chaperone cycle is tightly regulated by another group of proteins referred to as ‘co-chaperones'. Their stability does not depend on Hsp90 function but they interact with distinct Hsp90 conformational states, providing directionality to the Hsp90 cycle4. Furthermore, certain co-chaperones, such as HOP and Cdc37p50 inhibit the Hsp90 chaperone cycle, assisting in delivery of distinct sets of client proteins (steroid hormone receptors and kinases, respectively) to the Hsp90 chaperone machine.	SIGNOR-261412
P19086	P41146	2	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
Q01094	Q99608	2	binding	down-regulates activity	0.601	Necdin interacts with E2F transcription factors and suppresses E2F1-dependent transcriptional activation of the cyclin-dependent kinase Cdk1 gene. Here we show that necdin serves as a suppressor of NPC proliferation in the embryonic neocortex.	SIGNOR-253382
P01137	P01222	1	transcriptional regulation	down-regulates quantity by repression	0.2	TGF-Î² inhibits thyroid-stimulated hormone (TSH)-induced NIS mRNA and protein levels in a dose-dependent manner. This effect takes place at the transcriptional level, as TGF-Î² inhibits TSH-induced transcription	SIGNOR-251991
Q06124	Q99683	1	dephosphorylation	up-regulates	0.367	Previously we have shown that tyrosine 718 of ask1 when phosphorylated is critical for socs1 binding and socs1-mediated degradation of ask1we identified jak2 and shp2 as a tyr-718-specific kinase and phosphatase, respectively.	SIGNOR-184604
P23560	P16220	0	transcriptional regulation	up-regulates quantity	0.488	Brain-derived neurotrophic factor (BDNF) is a critical molecule for learning and memory. Brain BDNF levels correlate with cognitive status. Activation of CREB facilitates the transcription of crucial proteins for activity-dependent plasticity particularly BDNF.	SIGNOR-265062
P78527	P15927	1	phosphorylation	down-regulates activity	0.579	We showed previously that UV irradiation increases phosphorylation of the p34 subunit of human replication protein A (RPA) and that this hyperphosphorylation correlated with loss of activity of the DNA replication complex. \| we detected phosphorylation of the RPA complex by DNA-PK on RPA-p34 sites Ser-23, Ser-29, and Ser-11, -12, or -13	SIGNOR-248981
Q9Y210	Q13976	0	phosphorylation	down-regulates activity	0.491	PKG phosphorylated TRPC6, and both T70 and S322 were targeted. Both sites were functionally relevant, as 8Br-cGMP strongly suppressed current in wild-type TRPC6 channels, but not in those with phospho-silencing mutations (T70A, S322A or S322Q).	SIGNOR-276271
Q96EP1	Q14527	1	polyubiquitination	down-regulates quantity by destabilization	0.482	CHFR functions as a ubiquitin ligase for HLTF to regulate its stability and functions. CHFR negatively regulates and ubiquitinates HLTF. Taken together, this is the first report identifying the regulatory mechanism of HLTF by CHFR, suggesting that CHFR-mediated downregulation of HLTF may help protect against cancer.	SIGNOR-271460
O00755	P09238	1	transcriptional regulation	up-regulates quantity by expression	0.2	We first proved that Wnt7a activated the canonical Wnt pathway through direct regulation of the MMP10 gene.	SIGNOR-278867
Q01813	Q9Y4P1	1	phosphorylation	up-regulates activity	0.2	In vitro kinase assay validated that PFKP functioning as a protein kinase phosphorylated ATG4B at S34. This phosphorylation could enhance ATG4B activity and p62 degradation. In addition, PFKP S386 phosphorylation was important to ATG4B S34 phosphorylation and autophagy in HEK293T cells.	SIGNOR-275832
P60953	P42768	2	binding	up-regulates activity	0.957	Cdc42 can induce Arp2/3-mediated filopodia formation through the activation of WASp (Wiskott-Aldrich syndrome proteins) and neuronal N-WASp (Rohatgi et al., 1999). Similarly, Rac1-enhanced lamellipodia formation is related to Arp2/3 activation by the WAVE (WASP-family verprolin-homologous) complex	SIGNOR-261869
Q8IXL6	Q13316	1	phosphorylation	up-regulates quantity	0.659	Fam20c knockdown decreased Dmp1 mRNA and increased Fgf23 mRNA in UMR-106 cells.\|Relative migration distances of OPN and DMP1, which were the ratio of the migration distances of OPN or DMP1 co-expressed with mutant FAM20C to that with WT FAM20C, showed that only WT FAM20C could fully phosphorylate OPN and DMP1.	SIGNOR-280011
P10828	P28702	2	binding	up-regulates	0.636	Like many receptors belonging to the superfamily of steroid/thyroid nuclear receptors, thyroid hormone receptors (trs) bind to specific th-dna responsive elements (tre) upstream of target gene in heterodimeric complex with the 9-cis retinoid acid receptor (rxr	SIGNOR-81455
O14746	P31749	0	phosphorylation	up-regulates	0.732	Akt kinase enhances human telomerase activity through phosphorylation of htert subunit as one of its substrate proteins.	SIGNOR-67313
O14965	P30305	1	phosphorylation	up-regulates	0.722	We show that bypass of the g2/m checkpoint by the chk1 kinase inhibitor ucn-01 results in the activation of aurora-a and phosphorylation of cdc25b on s353	SIGNOR-139396
Q16763	P31749	0	phosphorylation	up-regulates quantity by stabilization	0.437	Mechanistically, Akt1 physically interacted with and phosphorylated UBE2S at Thr 152, enhancing its stability by inhibiting proteasomal degradation.	SIGNOR-265078
Q8IWT3	O15392	1	ubiquitination	down-regulates quantity	0.489	CUL9 promotes the ubiquitylation and degradation of survivin and is inhibited by CUL7.\|Together, these results demonstrate the specificity of survivin ubiquitylation by CUL9 E3 ligase complex.	SIGNOR-278808
P17252	Q969H0	1	phosphorylation	down-regulates activity	0.345	Here, we report that Fbw7α, the only Fbw7 isoform detected in eggs, is phosphorylated by PKC (protein kinase C) at a key residue (S18) in a manner coincident with Fbw7α inactivation.	SIGNOR-277249
Q96A56	O95166	2	binding	up-regulates	0.345	Tp53inp1 is also able to interact with atg8-family proteins	SIGNOR-196664
P01106	Q9NVW2	0	ubiquitination	down-regulates quantity by destabilization	0.37	This suggests that RLIM negatively regulates the transcriptional activity of c-Myc.\|We further showed that RLIM can promote polyubiquitination of c-Myc in cells.	SIGNOR-278551
P00519	O95433	1	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
P00519	P42345	1	phosphorylation	down-regulates	0.453	Abl binds directly to raft1 and phosphorylates raft1 in vitro and in vivo. c-abl inhibits autophosphorylation of raft1 and raft1-mediated phosphorylation p70(s6k).	SIGNOR-76562
P29317	Q13239	2	binding	down-regulates quantity by destabilization	0.414	These data are consistent with a model where SLAP induces Ephrin-independent EPHA2 degradation. \| This activity is independent from CBL but requires SLAP SH3 interaction with the ubiquitination factor UBE4A and SLAP SH2 interaction with pTyr594-EPHA2.	SIGNOR-262964
O75473	Q6UXX9	2	binding	up-regulates	0.693	Here we demonstrate that lgr4 and lgr5 bind the r-spondins with high affinity and mediate the potentiation of wnt/betBeta-catenin signaling by enhancing wnt-induced lrp6 phosphorylation	SIGNOR-174532
Q9NR96	P58753	2	binding	up-regulates activity	0.439	To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group	SIGNOR-266748
P17677	Q6UB99	0	transcriptional regulation	up-regulates quantity by expression	0.2	Neurite growth-related genes such as Trkb, Bdnf, Gap43, Coronin 1B, and Rab13 are downregulated in ANKRD11-deficient neurons.	SIGNOR-266736
P48730	Q9Y6Q9	1	phosphorylation	up-regulates	0.284	In this study, we show that both eralpha and aib1 are substrates for ck1delta in vitro, and identify a novel aib1 phosphorylation site (s601) targeted by ck1delta, significant for the co-activator function of aib1.	SIGNOR-184946
Q9UL54	O14733	2	binding	up-regulates	0.2	Immunoprecipitated psk phosphorylates myelin basic protein and transfected psk stimulates mkk4 and mkk7 and activates the c-jun n-terminal kinase mitogen-activated protein kinase pathway.	SIGNOR-74867
P14416	P41732	2	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

Q16543

P19784

0

phosphorylation

up-regulates activity

0.489

Phosphorylation of serine 13 is required for the proper function of the Hsp90 co-chaperone, Cdc37. | In this report, we demonstrate that mammalian Cdc37 is phosphorylated on Ser13 in situ in rabbit reticulocyte lysate and in cultured K562 cells and that casein kinase II is capable of quantitatively phosphorylating recombinant Cdc37 at this site.

SIGNOR-250982

O95837

P35348

2

binding

up-regulates activity

0.435

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257195

Q13153

O14950

1

phosphorylation

up-regulates activity

0.484

It has been shown that PAK1 phosphorylates and activates MLC2, leading to cell motility [ xref ].

SIGNOR-280053

P41597

P13500

2

binding

up-regulates activity

0.786

The investigators showed that myoblasts constitutively express receptors for CCL2 (CCR2), CCL3 (CCR1 and CCR5), and CCL4 (CCR5), and that stimulation with either CCL2 or CCL4 was sufficient to promote myoblast proliferation.

SIGNOR-255113

Q13542

P42345

0

phosphorylation

down-regulates

0.661

Here, we show that cancer cells acquire resistance to astori by downregulating eukaryotic translation initiation factor (eif4e)-binding proteins (4e-bps-eif4ebp1, eif4ebp2).

SIGNOR-122014

P17612

P52565

1

phosphorylation

down-regulates

0.387

The results indicate that phosphorylation of gdi_ at ser174 by pka suppresses rhoa activity, providing a potential protective signaling mechanism for inflammatory injury.

SIGNOR-180576

P23759

Q03164

2

binding

up-regulates

0.2

Carm1 specifically methylates multiple arginines in the n-terminus of pax7. Methylated pax7 directly binds the c-terminal cleavage forms of the trithorax proteins mll1/2 resulting in the recruitment of the ash2l:mll1/2:wdr5:rbbp5 histone h3k4 methyltransferase complex to regulatory enhancers and the proximal promoter of myf5.

SIGNOR-198626

Q9C0B5

P06241

0

phosphorylation

up-regulates quantity by stabilization

0.388

Our study demonstrates that under basal conditions, PSD-95 and Fyn cooperatively stabilize DHHC5 at the synaptic membrane through Fyn-mediated phosphorylation of DHHC5 at tyrosine residue 533 and the subsequent inhibition of DHHC5 association with endocytic proteins (Fig. 10).

SIGNOR-279738

P53350

P12830

1

phosphorylation

down-regulates quantity by destabilization

0.297

Priming phosphorylation of Cdh1 by the Cdk2/cyclin A kinase complex allows Plk1 to bind to Cdh1 and phosphorylate Cdh1 at Ser138 and Ser146. Phosphorylation of Cdh1 at Ser138 and Ser146 then triggers its interaction with, and subsequent ubiquitination by, SCFbeta-TRCP

SIGNOR-274054

P37840

P43405

0

phosphorylation

down-regulates

0.532

Here, we show that alpha-synuclein (alpha-syn) is an outstanding substrate for the protein tyrosine kinase p72syk (syk), which phosphorylates three tyrosyl residues in its c-terminal domain (y-125, y-133, and y-136), here, we show that _-syn is an outstanding substrate for syk and that once it is tyrosine phosphorylated, it loses the ability to form oligomers.

SIGNOR-113065

P15941

O43474

2

binding

up-regulates activity

0.281

Previous work has shown that the Kruppel-like factor 4 (KLF4) transcription factor represses p53 transcription by binding to the PE21 element. Our results show that MUC1-C binds constitutively to KLF4, occupies PE21 with KLF4, and enhances the KLF4 occupancy of PE21.

SIGNOR-270543

P01308

P08069

2

binding

up-regulates

0.89

Because of the sequence homology and tertiary structure similarities between proinsulin (pi) and insulin-like growth factor-i (igf-i), it is possible that pi interacts with the igf-i receptor with higher affinity than insulin.

SIGNOR-22083

Q9GZM8

P60510

0

dephosphorylation

down-regulates activity

0.395

Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation|PP4c selectively dephosphorylates NDEL1 at Cdk1 sites. We also demonstrate that PP4c negatively regulates Cdk1 activity at the centrosome.|We next examined the ability of PP4c to dephosphorylate a Cdk1 phosphorylation site, phospho-T219

SIGNOR-248550

P01111

Q07889

0

guanine nucleotide exchange factor

up-regulates activity

0.78

Sos and Ras-GRF are two families of guanine nucleotide exchange factors that activate Ras proteins in cells. Sos proteins are ubiquitously expressed and are activated in response to cell-surface tyrosine kinase stimulation Sos1 and Ras-GRF1 activate the Ras proteins Ha-Ras, N-Ras, and Ki-Ras

SIGNOR-110566

P31749

P48431

1

phosphorylation

up-regulates quantity by stabilization

0.532

In contrast, phosphorylation of Sox2 by AKT1 at T118 blocks K119me by Set7 and stabilizes Sox2.

SIGNOR-279003

Q13469

P19883

1

transcriptional regulation

up-regulates quantity by expression

0.2

MyoD, CREB, and NFAT Mediate the Transcriptional Activation of the Follistatin Promoter Induced by TSA

SIGNOR-251729

Q9NRC8

P22087

1

deacetylation

up-regulates activity

0.271

Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7.|hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromising H2AQ104 methylation (H2AQ104me) and rDNA transcription. SIRT7-dependent deacetylation of FBL ensures H2AQ104me and high levels of rRNA synthesis during interphase. |Global acetylome studies have shown that FBL is acetylated at four conserved lysine residues (K102, K121, K205, and K206)

SIGNOR-275894

Q9UHC6

Q6ZVD7

0

transcriptional regulation

down-regulates quantity by repression

0.2

In this study we performed chromatin immunoprecipitation coupled to shotgun cloning to discover novel STOX1A target genes. Our results show that CNTNAP2, a member of the neurexin family, is directly downregulated by STOX1A.

SIGNOR-269065

Q9NVD7

P28482

0

phosphorylation

up-regulates activity

0.259

Actopaxin (alpha-parvin) is a paxillin, integrin-linked kinase, and F-actin binding focal adhesion protein with several serine phosphorylation sites in the amino terminus that contribute to the regulation of cell spreading and migration.|Actopaxin phosphorylation of Ser4/8 enhances cell migration whereas a nonphosphorylatable (Quint) mutant suppresses migration in U2OS osteosarcoma cells (7).

SIGNOR-265759

P10589

P22888

1

transcriptional regulation

down-regulates quantity by repression

0.275

Functional analysis showed that EAR2 and EAR3/COUP-TFI repressed the hLHR promoter activity, whereas TR4 activated hLHR gene transcription.

SIGNOR-266218

O75376

P31749

0

phosphorylation

down-regulates

0.424

Akt-induced phosphorylation of n-cor at serine 1450 contributes to its misfolded conformational dependent loss (mcdl) in acute myeloid leukemia of the m5 subtype.

SIGNOR-198913

P54132

Q8IYW5

0

ubiquitination

up-regulates activity

0.262

Here, we demonstrate that the ubiquitin/SUMO-dependent DNA damage response (UbS-DDR), controlled by the E3 ligases RNF8/RNF168, triggers BLM recruitment to sites of replication fork stalling via ubiquitylation in the N-terminal region of BLM and subsequent BLM binding to the ubiquitin-interacting motifs of RAP80.

SIGNOR-272114

P00533

Q8ND25

1

phosphorylation

up-regulates activity

0.27

Together, these results demonstrate that EGFR-dependent phosphorylation of ZNRF1 at Y103 promotes degradation of AKT and resultant activation of GSK3\u03b2, which mediates oxidative stress\u2013induced neuronal apoptosis ( xref ).

SIGNOR-279522

P04637

Q15759

0

phosphorylation

up-regulates

0.611

We show that prak activates p53 by direct phosphorylation.

SIGNOR-152843

O43586

P50570

2

binding

down-regulates

0.374

We show that pstpip1 associates with the regulator of endocytosis, dynamin 2, and pstpip1 expression impairs transferrin uptake and endocytosis

SIGNOR-178628

Q13200

Q05086

0

ubiquitination

down-regulates quantity by destabilization

0.277

Our experiments collectively suggest that UBE3A stimulates Wnt pathway activation by interacting with, ubiquitinating, and reducing the levels of multiple (PSMB1, PSMC2, PSMD2, and PSMD7) proteasome subunits.

SIGNOR-265133

P50148

P34998

2

binding

up-regulates activity

0.286

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

SIGNOR-268619

P78545

Q13153

0

phosphorylation

up-regulates

0.456

Phosphorylation-dependent regulation of stability and transforming potential of ets transcriptional factor ese-1 by p21-activated kinase 1. Pak1 selectively phosphorylates ese-1 at ser(207). Intriguingly, pak1 phosphorylation inactive mutant ese1-s207a is more unstable

SIGNOR-154743

Q9BPV8

P30679

2

binding

up-regulates activity

0.2

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257143

Q96T88

P24941

0

phosphorylation

down-regulates quantity by destabilization

0.303

UHRF1 is phosphorylated by CDK2/cyclin A. In vitro kinase assay was performed with CDK2/cyclin A using recombinant wild-type UHRF1 or UHRF1-S674A mutant

SIGNOR-277192

Q01543

Q13547

0

deacetylation

up-regulates

0.2

Hdac1 interacts with fli1 and mediates its deacetylation / our previous studies have shown that pcaf-dependent acetylation of fli1 at lysine 380 decreases its protein stability / p300 promotes the interaction of fli1 with hdac1 and increases the dna binding ability of fli1 through deacetylation of lysine 380

SIGNOR-202689

P68400

P18146

1

phosphorylation

down-regulates activity

0.464

Casein kinase II associates with Egr-1 and acts as a negative modulator of its DNA binding and transcription activities in NIH 3T3 cells. | There are three CKII recognition sites (S376XXD, T389XE, and T516XXXD) in fragment 10.

SIGNOR-250858

O14965

P55072

2

binding

down-regulates activity

0.313

The UBXN-2/p37/p47 adaptors of CDC-48/p97 regulate mitosis by limiting the centrosomal recruitment of Aurora A.|We found that UBXN-2 and CDC-48 coimmunoprecipitated with AIR-1 from embryonic extracts

SIGNOR-265044

P25098

O95398

1

phosphorylation

down-regulates activity

0.2

The observation that GRK2 co-immunoprecipitates with Epac1 suggests a direct association between GRK2 and Epac1 in DRGs. xref A detailed study of the influence of GRK2 on the Epac1 level found that phosphorylation of ser108 in Epac1 by GRK2 can lead to a reduction of Epac1 activation. xref Downstream consequence of a reduction of GRK2 was explored. xref Low GRK2 expression in GRK2(\u00b1) DRGs was found to facilitate CPT-induced Rap1 activation and increase the phosphorylated ERK1/2 level.

SIGNOR-280001

Q96DX5

P12277

1

polyubiquitination

down-regulates quantity by destabilization

0.683

We demonstrate that creatine kinase B (CKB) interacts with Asb-9 in a specific, SOCS box-independent manner. This interaction increases the polyubiquitylation of CKB and decreases total CKB levels within the cell. The targeting of CKB for degradation by Asb-9 was primarily SOCS box-dependent and suggests that Asb-9 acts as a specific ubiquitin ligase regulating levels of this evolutionarily conserved enzyme.

SIGNOR-271623

P15735

P46019

2

binding

down-regulates activity

0.916

Phk is among the most complex of the protein kinases so far elucidated. It has one catalytic (gamma) subunit and three different regulatory (alpha, beta, and delta) subunits, a molecular mass of 1.3 X 106 daltons, and each holoenzyme molecule is presumed to contain four molecules of each subunit. The three regulatory subunits inhibit the phosphotransferase activity of the gamma subunit.

SIGNOR-267406

Q9UQM7

P29475

1

phosphorylation

down-regulates activity

0.471

It was found that purified recombinant nNOS was phosphorylated by CaM-K Ialpha, CaM-K IIalpha, and CaM-K IV at Ser847 in vitro. Replacement of Ser847 with Ala (S847A) prevented phosphorylation by CaM kinases. Phosphorylated recombinant wild-type nNOS at Ser847 (approximately 0.5 mol of phosphate incorporation into nNOS) exhibited a 30% decrease of Vmax with little change of both the Km for L-arginine and Kact for CaM relative to unphosphorylated enzyme. The activity of mutant S847D was decreased to a level 50-60% as much as the wild-type enzyme. The decreased NOS enzyme activity of phosphorylated nNOS at Ser847 and mutant S847D was partially due to suppression of CaM binding, but not to impairment of dimer formation which is thought to be essential for enzyme activation.

SIGNOR-250635

Q92915

Q8NEV1

0

phosphorylation

up-regulates activity

0.269

Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents.

SIGNOR-275743

Q00653

P20749

2

binding

up-regulates

0.573

The cyclin d1 elevation is caused not by increased p65/p50 action but rather by increased nuclear activity of bcl-3-associated nf-kappab p50 and p52.

SIGNOR-146768

Q8ND76

P06493

0

phosphorylation

down-regulates activity

0.595

Therefore, CDK1 may trigger CFP1 degradation through some indirect mechanisms rather than CFP1 phosphorylation.|This result suggests that, although CDK1 triggers both phosphorylation and degradation of CFP1 protein, phosphorylation of CFP1 by CDK1 is not a prerequisite for its degradation during cell division.

SIGNOR-279012

P63096

P28335

2

binding

up-regulates activity

0.293

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-256734

Q9HC97

P09471

2

binding

up-regulates activity

0.25

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256996

Q15466

P10275

2

binding

down-regulates

0.415

We demonstrated that shp inhibited both ar-lbd and ntd-dependent transactivation, which evidenced for the first time a protein capable of inhibiting a steroid receptor amino-terminal-dependent transactivation. We further characterized the shp mechanism of action by showing that shp reversed ar coactivator-mediated activation

SIGNOR-112589

P12931

P20701

1

phosphorylation

down-regulates activity

0.421

PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.

SIGNOR-254741

P15172

Q02363

2

binding

down-regulates activity

0.54

Id1 and Id2 interacted strongly with MyoD and Myf-5.Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo.

SIGNOR-240268

P16403

O76064

0

polyubiquitination

down-regulates

0.2

ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2.

SIGNOR-272928

P78527

P50876

0

polyubiquitination

down-regulates quantity by destabilization

0.568

We show that RNF144A induces ubiquitination of DNA-PKcs in vitro and in vivo and promotes its degradation.

SIGNOR-272213

Q6ZNA4

P61956

1

polyubiquitination

down-regulates quantity by destabilization

0.626

Arkadia ubiquitinates poly-SUMO2 chains in a SIM- and RING-dependent manner.

SIGNOR-272882

P52948

P59634

2

binding

down-regulates activity

0.2

Orf6 of SARS-CoV antagonizes host interferon signaling by perturbing nuclear transport, and the NUP98-RAE1 interaction with Orf6 may perform the same function for SARS-CoV-2.

SIGNOR-260976

Q05397

Q05209

0

dephosphorylation

down-regulates activity

0.538

We demonstrate here that activated Ras induces tyrosine dephosphorylation and inhibition of FAK mediated by the Ras downstream Fgd1-Cdc42-PAK1-MEK-ERK signaling cascade.| PIN1 binding and prolyl isomerization of FAK cause PTP-PEST to interact with and dephosphorylate FAK Y397. Inhibition of FAK mediated by this signal relay promotes Ras-induced cell migration, invasion, and metastasis.

SIGNOR-248661

Q86V86

Q92934

1

phosphorylation

down-regulates activity

0.346

Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. pim kinases are constitutively active when expressed in HEK-293 cells and are able to phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and Ser155 in vitro and in cells.

SIGNOR-250399

P10828

P27361

0

phosphorylation

down-regulates activity

0.428

We concluded that serine 142 of the tr dbd is the likely site of phosphorylation by t(4)-activated mapk and that the docking site on tr for activated mapk includes residues 128-133 (kgffrr), a basic amino acid-enriched motif novel for mapk substrates. Tr mutations in the proposed mapk docking domain and at residue 142 modulated t(4)-conditioned shedding of co-repressor and recruitment of co-activator proteins by the receptor, and they altered transcriptional activity of tr in a thyroid hormone response element-luciferase reporter assay.

SIGNOR-102224

Q99661

Q13153

0

phosphorylation

down-regulates

0.385

Here we found that mcak is a cognate substrate of pak1 wherein pak1 phosphorylates mcak on serines 192 and 111 both in vivo and in vitro. Furthermore, we found that pak1 phosphorylation of mcak on serines 192 and 111 preferentially regulates its microtubule depolymerization activity and localization to centrosomes

SIGNOR-199084

Q96SB3

P17612

0

phosphorylation

down-regulates activity

0.31

Spinophilin is phosphorylated in vitro by protein kinase A (PKA). two major sites of phosphorylation, Ser-94 and Ser-177, that are located within the actin-binding domain of spinophilin. Phosphorylation of spinophilin by PKA modulated the association between spinophilin and the actin cytoskeleton. phosphorylation of spinophilin reduced the stoichiometry of the spinophilin-actin interaction. In contrast, the ability of spinophilin to bind to PP1 remained unchanged.

SIGNOR-250035

Q86TM6

Q16236

1

ubiquitination

down-regulates quantity by destabilization

0.2

NRF2 is negatively regulated by three E3 ubiquitin ligase complexes: the KEAP1-CUL3-RBX1 complex, the β-TrCP-SKP1-CUL1-RBX1 complex, and HRD1.

SIGNOR-267360

P16333

P00533

2

binding

up-regulates activity

0.576

We show that epidermal growth factor or platelet-derived growth factor stimulation of intact human or murine cells leads to phosphorylation of Nck protein on tyrosine, serine, and threonine residues

SIGNOR-252089

Q96SN8

O95613

2

binding

up-regulates activity

0.819

Our observation that Cep215 may function downstream of pericentrin suggests that the two proteins affect centrosome cohesion through a common mechanism. |Finally, depletion of pericentrin caused an almost complete loss of Cep215 from centrosomes, a detectable reduction in centrosomal levels of Cep68 and rootletin, but no significant effect on C-Nap1 (Fig. 6C and Table 1). Taken together, these results point to functional (and perhaps molecular) interactions between (1) Cep68 and rootletin and (2) Cep215 and pericentrin.

SIGNOR-260309

P13501

P51681

2

binding

up-regulates activity

0.937

CCL5, also known RANTES (regulated on activation, normal T cell expressed and secreted), is a potent chemoattractant for a variety of leukocytes, including T cells, mono- cytes, NK cells, and basophils, signaling via the CCR1, CCR3, and CCR5 cell surface receptors [59]. Among these receptors, CCL5 has the highest affinity for CCR5.

SIGNOR-277726

P27361

P48431

1

phosphorylation

down-regulates activity

0.452

Mass spectrum analysis was employed after an in vitro kinase assay in which cells were incubated with or without ERK1-active kinase, and the results demonstrated that Sox2 was phosphorylated by ERK1 directly at S251, which was further verified by western blotting for the specific antibody targeting S251 phosphorylated Sox2 after the in vitro kinase assay.|Mechanistically, ERK1 kinase promoted autophagic degradation of Sox2 via phosphorylation of Sox2 at Ser251 and further SUMOylation of Sox2 at Lys245 in non CSCs.

SIGNOR-279071

P36941

Q12933

2

binding

up-regulates activity

0.586

Endogenous association of traf2, traf3, ciap1, and smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis.

SIGNOR-97950

Q5S007

Q96CW1

1

phosphorylation

up-regulates activity

0.259

These data confirmed that LRRK2 phosphorylates AP2M1 at Thr 156 in vitro.

SIGNOR-278183

Q12778

P30304

0

dephosphorylation

up-regulates activity

0.313

In this study, we revealed that Cdc25A enhances Foxo1 stability by dephosphorylating Cdk2, and Foxo1 was shown to directly regulate transcription of the metastatic factor MMP1.

SIGNOR-277139

P63096

Q96P68

2

binding

up-regulates activity

0.385

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-257042

P45983

Q13526

1

phosphorylation

up-regulates quantity by stabilization

0.272

Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation.

SIGNOR-277562

P35900

P49137

0

phosphorylation

up-regulates activity

0.2

P38 phosphorylates the type II keratin, K8 at Ser73, whereas MK2 phosphorylates the binding partners K18 at Ser52 and K20 at Ser13.

SIGNOR-263071

Q9NQL2

Q8NFG4

0

gtpase-activating protein

up-regulates activity

0.683

The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1 [..} RagC/D is a key regulator of the interaction of mTORC1 with the Rag heterodimer and that, unexpectedly, RagC/D must be GDP-bound for the interaction to occur

SIGNOR-256504

P20309

O95837

2

binding

up-regulates activity

0.411

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-257134

P42574

Q4V328

1

cleavage

up-regulates activity

0.414

These results suggest that the region of GRASP‐1 downstream of the Caspase‐3‐cleavage site is capable of activating the JNK signaling pathway by enhancing the phosphorylation of JNK. these results suggest that full length GRASP‐1 does not enhance JNK pathway activity, possibly due to the inhibitory effect of the N‐terminal fragment on the C‐terminal fragment. In contrast, Caspase‐3 cleavage of GRASP‐1 releases the C‐terminal fragment, which in turn activates JNK signaling by serving as a scaffold protein.

SIGNOR-260641

P40763

Q14289

0

phosphorylation

up-regulates activity

0.428

These results imply that following EGF stimulation, PYK2 enhances a STAT3-dependent IL8 expression, thus creating a positive feedback loop between ErbB receptors, PYK2, and IL8.|These results suggest that PYK2-induced STAT3 phosphorylation is crucial for IL8 secretion, while IL8 is crucial for EGF-induced MMP9 transcription (Figure xref ) and for SKBR3 invasion (Figure xref ).

SIGNOR-279429

Q96DT5

Q92949

0

transcriptional regulation

up-regulates quantity by expression

0.361

FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).

SIGNOR-266931

P31948

P08238

2

binding

down-regulates activity

0.855

Hsp90 chaperone cycle is tightly regulated by another group of proteins referred to as ‘co-chaperones'. Their stability does not depend on Hsp90 function but they interact with distinct Hsp90 conformational states, providing directionality to the Hsp90 cycle4. Furthermore, certain co-chaperones, such as HOP and Cdc37p50 inhibit the Hsp90 chaperone cycle, assisting in delivery of distinct sets of client proteins (steroid hormone receptors and kinases, respectively) to the Hsp90 chaperone machine.

SIGNOR-261412

P19086

P41146

2

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

Q01094

Q99608

2

binding

down-regulates activity

0.601

Necdin interacts with E2F transcription factors and suppresses E2F1-dependent transcriptional activation of the cyclin-dependent kinase Cdk1 gene. Here we show that necdin serves as a suppressor of NPC proliferation in the embryonic neocortex.

SIGNOR-253382

P01137

P01222

1

transcriptional regulation

down-regulates quantity by repression

0.2

TGF-Î² inhibits thyroid-stimulated hormone (TSH)-induced NIS mRNA and protein levels in a dose-dependent manner. This effect takes place at the transcriptional level, as TGF-Î² inhibits TSH-induced transcription

SIGNOR-251991

Q06124

Q99683

1

dephosphorylation

up-regulates

0.367

Previously we have shown that tyrosine 718 of ask1 when phosphorylated is critical for socs1 binding and socs1-mediated degradation of ask1we identified jak2 and shp2 as a tyr-718-specific kinase and phosphatase, respectively.

SIGNOR-184604

P23560

P16220

0

transcriptional regulation

up-regulates quantity

0.488

Brain-derived neurotrophic factor (BDNF) is a critical molecule for learning and memory. Brain BDNF levels correlate with cognitive status. Activation of CREB facilitates the transcription of crucial proteins for activity-dependent plasticity particularly BDNF.

SIGNOR-265062

P78527

P15927

1

phosphorylation

down-regulates activity

0.579

We showed previously that UV irradiation increases phosphorylation of the p34 subunit of human replication protein A (RPA) and that this hyperphosphorylation correlated with loss of activity of the DNA replication complex. | we detected phosphorylation of the RPA complex by DNA-PK on RPA-p34 sites Ser-23, Ser-29, and Ser-11, -12, or -13

SIGNOR-248981

Q9Y210

Q13976

0

phosphorylation

down-regulates activity

0.491

PKG phosphorylated TRPC6, and both T70 and S322 were targeted. Both sites were functionally relevant, as 8Br-cGMP strongly suppressed current in wild-type TRPC6 channels, but not in those with phospho-silencing mutations (T70A, S322A or S322Q).

SIGNOR-276271

Q96EP1

Q14527

1

polyubiquitination

down-regulates quantity by destabilization

0.482

CHFR functions as a ubiquitin ligase for HLTF to regulate its stability and functions. CHFR negatively regulates and ubiquitinates HLTF. Taken together, this is the first report identifying the regulatory mechanism of HLTF by CHFR, suggesting that CHFR-mediated downregulation of HLTF may help protect against cancer.

SIGNOR-271460

O00755

P09238

1

transcriptional regulation

up-regulates quantity by expression

0.2

We first proved that Wnt7a activated the canonical Wnt pathway through direct regulation of the MMP10 gene.

SIGNOR-278867

Q01813

Q9Y4P1

1

phosphorylation

up-regulates activity

0.2

In vitro kinase assay validated that PFKP functioning as a protein kinase phosphorylated ATG4B at S34. This phosphorylation could enhance ATG4B activity and p62 degradation. In addition, PFKP S386 phosphorylation was important to ATG4B S34 phosphorylation and autophagy in HEK293T cells.

SIGNOR-275832

P60953

P42768

2

binding

up-regulates activity

0.957

Cdc42 can induce Arp2/3-mediated filopodia formation through the activation of WASp (Wiskott-Aldrich syndrome proteins) and neuronal N-WASp (Rohatgi et al., 1999). Similarly, Rac1-enhanced lamellipodia formation is related to Arp2/3 activation by the WAVE (WASP-family verprolin-homologous) complex

SIGNOR-261869

Q8IXL6

Q13316

1

phosphorylation

up-regulates quantity

0.659

Fam20c knockdown decreased Dmp1 mRNA and increased Fgf23 mRNA in UMR-106 cells.|Relative migration distances of OPN and DMP1, which were the ratio of the migration distances of OPN or DMP1 co-expressed with mutant FAM20C to that with WT FAM20C, showed that only WT FAM20C could fully phosphorylate OPN and DMP1.

SIGNOR-280011

P10828

P28702

2

binding

up-regulates

0.636

Like many receptors belonging to the superfamily of steroid/thyroid nuclear receptors, thyroid hormone receptors (trs) bind to specific th-dna responsive elements (tre) upstream of target gene in heterodimeric complex with the 9-cis retinoid acid receptor (rxr

SIGNOR-81455

O14746

P31749

0

phosphorylation

up-regulates

0.732

Akt kinase enhances human telomerase activity through phosphorylation of htert subunit as one of its substrate proteins.

SIGNOR-67313

O14965

P30305

1

phosphorylation

up-regulates

0.722

We show that bypass of the g2/m checkpoint by the chk1 kinase inhibitor ucn-01 results in the activation of aurora-a and phosphorylation of cdc25b on s353

SIGNOR-139396

Q16763

P31749

0

phosphorylation

up-regulates quantity by stabilization

0.437

Mechanistically, Akt1 physically interacted with and phosphorylated UBE2S at Thr 152, enhancing its stability by inhibiting proteasomal degradation.

SIGNOR-265078

Q8IWT3

O15392

1

ubiquitination

down-regulates quantity

0.489

CUL9 promotes the ubiquitylation and degradation of survivin and is inhibited by CUL7.|Together, these results demonstrate the specificity of survivin ubiquitylation by CUL9 E3 ligase complex.

SIGNOR-278808

P17252

Q969H0

1

phosphorylation

down-regulates activity

0.345

Here, we report that Fbw7α, the only Fbw7 isoform detected in eggs, is phosphorylated by PKC (protein kinase C) at a key residue (S18) in a manner coincident with Fbw7α inactivation.

SIGNOR-277249

Q96A56

O95166

2

binding

up-regulates

0.345

Tp53inp1 is also able to interact with atg8-family proteins

SIGNOR-196664

P01106

Q9NVW2

0

ubiquitination

down-regulates quantity by destabilization

0.37

This suggests that RLIM negatively regulates the transcriptional activity of c-Myc.|We further showed that RLIM can promote polyubiquitination of c-Myc in cells.

SIGNOR-278551

P00519

O95433

1

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

P00519

P42345

1

phosphorylation

down-regulates

0.453

Abl binds directly to raft1 and phosphorylates raft1 in vitro and in vivo. c-abl inhibits autophosphorylation of raft1 and raft1-mediated phosphorylation p70(s6k).

SIGNOR-76562

P29317

Q13239

2

binding

down-regulates quantity by destabilization

0.414

These data are consistent with a model where SLAP induces Ephrin-independent EPHA2 degradation. | This activity is independent from CBL but requires SLAP SH3 interaction with the ubiquitination factor UBE4A and SLAP SH2 interaction with pTyr594-EPHA2.

SIGNOR-262964

O75473

Q6UXX9

2

binding

up-regulates

0.693

Here we demonstrate that lgr4 and lgr5 bind the r-spondins with high affinity and mediate the potentiation of wnt/betBeta-catenin signaling by enhancing wnt-induced lrp6 phosphorylation

SIGNOR-174532

Q9NR96

P58753

2

binding

up-regulates activity

0.439

To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group

SIGNOR-266748

P17677

Q6UB99

0

transcriptional regulation

up-regulates quantity by expression

0.2

Neurite growth-related genes such as Trkb, Bdnf, Gap43, Coronin 1B, and Rab13 are downregulated in ANKRD11-deficient neurons.

SIGNOR-266736

P48730

Q9Y6Q9

1

phosphorylation

up-regulates

0.284

In this study, we show that both eralpha and aib1 are substrates for ck1delta in vitro, and identify a novel aib1 phosphorylation site (s601) targeted by ck1delta, significant for the co-activator function of aib1.

SIGNOR-184946

Q9UL54

O14733

2

binding

up-regulates

0.2

Immunoprecipitated psk phosphorylates myelin basic protein and transfected psk stimulates mkk4 and mkk7 and activates the c-jun n-terminal kinase mitogen-activated protein kinase pathway.

SIGNOR-74867

P14416

P41732

2

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