GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q96RI0	Q14344	1	binding	up-regulates	0.408	Upon proteolysis, the newly formed n terminus acts as a tethered ligand that activates the receptor and initiates signaling cascades through multiple g proteins (galfaq, galfai, and galfa12/13)	SIGNOR-196015
Q96J02	P17275	1	polyubiquitination	down-regulates quantity by destabilization	0.408	Itch promotes Ub conjugation to JunB Molecularly, Itch associated with and induced ubiquitination of JunB, a transcription factor that is involved in TH2 differentiation. However, in Itch−/− T cells under the same conditions, degradation of JunB was markedly delayed.	SIGNOR-272619
Q13627	Q01130	1	phosphorylation	down-regulates activity	0.408	Dyrk1A inhibits SC35\u2032s activity to promote tau exon 10 inclusion.\|Dyrk1A interacts with and phosphorylates SC35 and inhibits its activity to promote tau exon 10 inclusion.	SIGNOR-278307
P16144	Q01453	1	binding	up-regulates activity	0.408	PMP22 is in a complex with α6β4 integrin and laminin. PMP22 and β4 integrin are in a complex in a variety of cell types. The interaction with the integrins provides PMP22 with the ability to modulate the cell–ECM communications, as well as intracellular events. Signaling between the ECM and the intracellular compartment is essential for SC myelination, as well as cellular differentiation and motility, in general. The identification of PMP22 as a binding partner for an integrin signaling complex provides a major step toward understanding the role of this disease-linked molecule in the nervous system and in non-neural cell types.	SIGNOR-251896
Q9NPG1	P50148	1	binding	up-regulates	0.408	Gpcrs signal through four relatively small families of galfa proteins (galfas, galfai/o, galfaq, and galfa12/13), and if fzd receptors are classic gpcrs, they should signal through one of these four galfa families.	SIGNOR-122895
Q13554	Q14524	1	phosphorylation	up-regulates activity	0.408	Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate–activated protein kinase (AMPK)–dependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).\|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. \| Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5	SIGNOR-275773
Q8IXH6	Q9H492	1	binding	up-regulates	0.408	Tp53inp2 is a scaffold protein that recruits lc3 and/or lc3-related proteins to the autophagosome membrane by interacting with the transmembrane protein vmp1	SIGNOR-182614
Q96CN5	Q9BV73	1	binding	up-regulates activity	0.408	Here, we show that LRRC45 is a centrosome linker that localizes at the proximal ends of the centrioles and forms fiber-like structures between them. Depletion of LRRC45 results in centrosome splitting during interphase. LRRC45 interacts with C-Nap1 and rootletin	SIGNOR-273703
P68400	P30291	1	phosphorylation	down-regulates quantity by destabilization	0.408	In the present study, we show that phosphorylation of S123 (pS123) by CDK promoted the binding of Wee1A to beta-TrCP through three independent mechanisms. S123 phosphorylation creates a PBD-binding motif and accelerates S53 phosphorylation by Plk1.	SIGNOR-276038
Q16236	P00441	1	transcriptional regulation	up-regulates quantity by expression	0.408	BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2	SIGNOR-254653
Q16539	Q8TDD2	1	phosphorylation	up-regulates activity	0.408	We therefore propose that Osterix binds to Sp1 sequences on target gene promoters and that its phosphorylation by p38 enhances recruitment of coactivators to form transcriptionally active complexes	SIGNOR-255791
Q00535	O14490	1	phosphorylation	down-regulates quantity by destabilization	0.408	Taken together, these sets of data suggest that Abeta triggers the phosphorylation of GKAP by cdk5 at the serine residues S77 and S111 that in turn are crucial for GKAP degradation.	SIGNOR-279153
Q12947	P20226	1	binding	up-regulates activity	0.408	The human forkhead protein FREAC-2 contains two functionally redundant activation domains and interacts with TBP and TFIIB.	SIGNOR-220373
Q06710	Q92911	1	transcriptional regulation	up-regulates quantity by expression	0.408	Pax8 has an essential role in thyroid organogenesis and differentiation, being the main mediator of thyroid gene transcription, including the NIS gene.	SIGNOR-251990
P35813	Q16539	1	dephosphorylation	down-regulates activity	0.408	Moreover, when expressed in mammalian cells, pp2ca inhibited the activation of the p38 and jnk cascades induced by environmental stresses. Both in vivo and in vitro observations indicated that pp2ca dephosphorylated and inactivated mapkks (mkk6 and sek1) and a mapk (p38) in the stress-responsive mapk cascades. Furthermore, a direct interaction of pp2ca and p38 was demonstrated by a co-immunoprecipitation assay	SIGNOR-59618
P41231	P30679	1	binding	up-regulates activity	0.408	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-257031
P43405	P36888	1	phosphorylation	up-regulates activity	0.407	Only two mutants, FLT3-KD (V5) Y768A and Y955A, were resistant to SYK-mediated FLT3 phosphorylation, suggesting that SYK directly phosphorylates FLT3 at sites Y768 and Y955 ( ).\|SYK Enhances FLT3 WT and Mutant Activation by Phosphorylation of Residues Y768 and Y955.	SIGNOR-278431
Q9NUX5	P15927	1	binding	down-regulates activity	0.407	The current model for how telomeres repress ATR signaling proposes that POT1/TPP1 prevents the binding of RPA to the single-stranded telomeric DNA	SIGNOR-263324
P06493	Q15717	1	phosphorylation	down-regulates activity	0.407	Cdk1 inhibition promoted a cytoplasmic accumulation of HuR, while a predominately nuclear localization of HuR was observed under conditions of high Cdk1 activity.\|Kim et al. further showed that Cdk1-dependent Ser-202 phosphorylation of HuR was essential for 14-3-3\u03b8 binding to HuR.	SIGNOR-279014
P08575	P29597	1	dephosphorylation	down-regulates activity	0.407	CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling\|these results show that CD45 dephosphorylates functionally important tyrosine residues. It should be noted that, as with our phosphatase assays in vitro, Tyr 1022 and Tyr 1023 of JAK1, Tyr 1007 and Tyr 1008 of JAK2, and Tyr 1054 and Tyr 1055 of Tyk2 are indeed hyperphosphorylated in cd45-deficient cells	SIGNOR-248357
P12931	Q92558	1	phosphorylation	up-regulates	0.407	The wave/scar proteins regulate actin polymerisation at the leading edge of motile cells via activation of the arp2/3 complex in response to extracellular cues.Src-dependent phosphorylation of scar1 promotes its association with the arp2/3 complex	SIGNOR-142724
Q9UNW8	O95837	1	binding	up-regulates activity	0.407	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-257396
Q13255	P63092	1	binding	up-regulates activity	0.407	MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.	SIGNOR-264077
Q08881	P42680	1	phosphorylation	up-regulates	0.407	Tec family protein tyrosine kinases (tfks) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the sh3 domain via a transphosphorylation mechanism. Here, we could confirm that y223 is the only site in the btk-sh3 domain being detectably phosphorylated	SIGNOR-98090
Q8TDX7	P52732	1	phosphorylation	up-regulates activity	0.407	NEK7 regulates these processes in part through phosphorylation of the kinesin Eg5/KIF11, promoting its accumulation on microtubules in distal dendrites.	SIGNOR-273890
Q9UHD2	P31749	1	phosphorylation	up-regulates	0.407	Upon mitogen stimulation, triggering of the innate immune response, re-exposure to glucose, or oncogene activation, tbk1 is recruited to the exocyst, where it activates akt. Akt is a direct tbk1 substrate that connects tbk1 to prosurvival signaling.	SIGNOR-252608
O43561	P27986	1	binding	up-regulates activity	0.407	By substituting these tyrosine residues in LAT with phenylalanine and by utilizing phosphorylated peptides derived from these sites, we mapped the tyrosine residues in LAT required for the direct interaction and activation of Vav, p85/p110alpha and phospholipase Cgamma1 (PLCgamma1). Our results indicate that Tyr(226) and Tyr(191) are required for Vav binding, whereas Tyr(171) and Tyr(132) are necessary for association and activation of phosphoinositide 3-kinase activity and PLCgamma1 respectively.	SIGNOR-246050
Q9UNE7	Q13950	1	ubiquitination	down-regulates quantity by destabilization	0.407	Here, we show that CHIP promotes Runx2 ubiquitination and degradation and thereby negatively regulates osteoblast differentiation.	SIGNOR-278600
Q9Y448	Q8N4N8	1	relocalization	down-regulates activity	0.407	The protein astrin has been shown to remove Kif2b from kinetochores in metaphase through competitive binding of CLASP1 (Manning et al., 2010 blue right-pointing triangle). During prometaphase, Aurora B kinase activity prevents astrin from localizing to kinetochores (Manning et al., 2010 blue right-pointing triangle; Schmidt et al., 2010 blue right-pointing triangle). This permits Kif2b to localize to kinetochores to destabilize k-MT attachments to execute error correction through Plk1-dependent recruitment and activation.	SIGNOR-252053
Q13315	O15360	1	phosphorylation	up-regulates	0.407	The s1449a mutant failed to completely correct a variety of fa-associated phenotypes. The dna damage response is coordinated by phosphorylation events initiated by apical kinases atm (ataxia telangectasia mutated) and atr (atm and rad3-related), and atr is essential for proper fa pathway function. Serine 1449 is in a consensus atm/atr site	SIGNOR-182949
Q14164	O43524	1	phosphorylation	down-regulates	0.407	Ikbke phosphorylation and inhibition of foxo3a: a mechanism of ikbke oncogenic functionhere we report that ikbke regulates foxo3a through phosphorylation of foxo3a-ser644. The phosphorylation of foxo3a resulted in its degradation and nuclear-cytoplasmic translocation.	SIGNOR-202054
P10144	P11717	1	binding	up-regulates	0.407	The serine proteinase granzyme b is crucial for the rapid induction of target cell apoptosis by cytotoxic t cells. We now present evidence that this receptor is the cation-independent mannose 6-phosphate/insulin-like growth factor receptor (ci-mpr). Inhibition of the granzyme b ci-mpr interaction prevented granzyme b cell surface binding, uptake, and the induction of apoptosis.	SIGNOR-84314
P52333	O14939	1	phosphorylation	up-regulates	0.407	We identified three kinases capable of phosphorylating pld2 in vitro-epidermal growth factor receptor (egfr), jak3, and src (with jak3 reported for the first time in this study)-that phosphorylate an inhibitory, an activator, and an ambivalent (one that can yield either effect) site, respectively. Mass spectrometry analyses indicated the target of each of these kinases as y(296) for egfr, y(415) for jak3, and y(511) for src.	SIGNOR-163858
P06493	O15151	1	phosphorylation	down-regulates	0.407	Cdc2p34 phosphorylates mdmx on ser 96 in vitro. Mutation within this site (mdmx(s96a)) impairs, whereas phosphomimic substitution (mdmx(s96d)) increases the cytoplasmic localization of mdmx, suggesting that cdk2/cdc2p34 phosphorylation is required for export of mdmx from the nucleus	SIGNOR-134388
P31277	O00470	1	binding	up-regulates activity	0.407	We now show that the Hoxa-9 protein physically interacts with Meis1 proteins. Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.	SIGNOR-241229
Q99942	P49023	1	ubiquitination	down-regulates quantity	0.407	Here we demonstrate that the human homologue of RNF5 associates with the amino-terminal domain of paxillin, resulting in its ubiquitination. RNF5 requires intact RING and C-terminal domains to mediate paxillin ubiquitination. Concomitantly, RNF5 expression results in inhibition of cell motility. Via targeting of paxillin ubiquitination, which alters its localization, RNF5 emerges as a novel regulator of cell motility.	SIGNOR-271479
Q70Z35	P61586	1	guanine nucleotide exchange factor	up-regulates activity	0.406	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260570
O43293	P04637	1	phosphorylation	up-regulates	0.406	A cell-free ser(20) phosphorylation site assay was used to identify a broad range of calcium calmodulin kinase superfamily members, including chk2, chk1, dapk-1, dapk-3, drak-1, and ampk, as ser(20) kinases.Evaluation of these calcium calmodulin kinase superfamily members as candidate ser(20) kinases in vivo has shown that only chk1 or dapk-1 can stimulate p53 transactivation and induce ser(20) phosphorylation of p53.	SIGNOR-153495
Q13315	Q5XUX0	1	phosphorylation	up-regulates	0.406	We find that dna damage induced by gamma-irradiation results in increased fbxo31 levels, which requires phosphorylation of fbxo31 by the ddr-initiating kinase atm	SIGNOR-185635
Q12913	P28482	1	dephosphorylation	down-regulates	0.406	In this study we show that one of these potential targets, the erk1/2, is indeed a direct dep-1 substrate in vivo.	SIGNOR-161536
Q14653	P05231	1	transcriptional regulation	up-regulates quantity by expression	0.406	Recent reports show that in mice the microbiome, comprising commensal microorganisms that colonize body surfaces, promotes a partial and low-grade M1-like phenotype in macrophages throughout the body, including those in lymphoid organs (119, 120). This M1-like priming of macrophages induces chromatin remodeling with increased H3K4me3 marks at Ifnb, Il6, and Tnf promoters, which is associated with increased binding of NF-κB p65, IRF3, and Pol II upon cell stimulation	SIGNOR-251721
P12931	Q9UGK3	1	phosphorylation	up-regulates activity	0.406	To examine this possibility, STAP-2 was co-transfected with constitutively active tyrosine kinases in HEK-293 cells. STAP-2 was strongly phosphorylated by various tyrosine kinases, including v-Src (Fig.2 A-a), a JAK2 tyrosine kinase Tyr-22 and Tyr-322 are the major tyrosine phosphorylation sites by v-Src.	SIGNOR-247337
Q15154	Q8N4C6	1	relocalization	up-regulates	0.406	Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome	SIGNOR-95077
Q8TAS1	Q15637	1	phosphorylation	up-regulates	0.406	Sf1 is phosphorylated on serines 80 and 82 in vitro and in vivo. Kis can phosphorylate sf1f on serine 80 and 82 with a high efficiency that particularly relies on the anchoring of its uhm domain to sf1. Serine phosphorylation of a conserved ser80-pro81-ser82-pro83 motif rigidifies a long unstructured linker in the sf1 helix hairpin and slightly enhances rna binding.	SIGNOR-199797
Q16659	O60229	1	phosphorylation	up-regulates activity	0.406	The brain-specific nucleotide exchange factor kalirin-7 (Kal7) was identified as an MK5 interaction partner and substrate protein. The MK5 substrate Kal7, a Rho GEF and known activator of Rac GTPases, further contributes to PAK activation and actin filament reorganization. Thus, the coordinated phosphorylation of Borg proteins and Kal7 by ERK3 and MK5 constitute a novel signaling cascade involving feed-forward circuits, multiple GTPases, and cytoskeletal elements.	SIGNOR-263094
O15033	O43464	1	ubiquitination	down-regulates quantity by destabilization	0.406	Furthermore, the ubiquitination and degradation of SMAC, HtrA2, and ARTS were significantly enhanced in AREL1-expressing cells following apoptotic stimulation, indicating that AREL1 binds to and ubiquitinates cytosolic but not mitochondria-associated forms of IAP antagonists	SIGNOR-267669
P55085	P50148	1	binding	up-regulates activity	0.406	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-257300
P78527	P11831	1	phosphorylation	up-regulates activity	0.406	The carboxyl-terminal transcription activation domain was mapped within a 71-amino acid region that contains both DNA-PK phosphorylation sites. Amino acid substitutions that interfered with phosphorylation by DNA-PK at Ser-435/446 in GAL4-SRF fusion proteins were reduced in transactivation potency. From these data we suggest that DNA-PK phosphorylation may modulate SRF activity in vivo.	SIGNOR-248922
P35222	P15172	1	binding	up-regulates activity	0.406	Together, these results suggest that B-Cat increases MyoD binding to E box elements	SIGNOR-255653
Q06187	Q9UJV9	1	phosphorylation	up-regulates activity	0.406	The kinase and SH3/SH2 interaction domains of BTK bind, respectively, the DEAD-box domain of DDX41 and transmembrane region of STING. BTK phosphorylates DDX41, and its kinase activities are critical for STING-mediated IFN-β production. We show that Tyr364 and Tyr414 of DDX41 are critical for its recognition of AT-rich DNA and binding to STING, and tandem mass spectrometry identifies Tyr414 as the BTK phosphorylation site.	SIGNOR-266404
P17612	Q5S007	1	phosphorylation	down-regulates activity	0.406	Furthermore, our work establishes S1444 as a PKA-regulated 14-3-3 docking site.Strikingly, 14-3-3 binding to phospho-S1444 decreased LRRK2 kinase activity in vitro.	SIGNOR-237444
P45984	P55957	1	phosphorylation	up-regulates activity	0.406	(c) The phosphorylation of recombinant Bid by JNK2 (in vitro kinase assay) prevents its cleavage by caspase-8	SIGNOR-279220
O75385	Q9UGI9	1	phosphorylation	down-regulates	0.406	Ulk1/2 in turn phosphorylates all three subunits of ampk and thereby negatively regulates its activity phosphorylation of ampk by ulk1 represents a negative feedback circuit.	SIGNOR-173053
Q6IQ55	O00139	1	phosphorylation	down-regulates activity	0.406	TTBK2 phosphorylates KIF2A primarily at growing MT ends and counteracts the depolymerization activity of KIF2A	SIGNOR-260926
Q15154	Q12798	1	relocalization	up-regulates	0.406	Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome	SIGNOR-94947
Q9NWF9	Q9NR96	1	ubiquitination	down-regulates quantity by destabilization	0.406	Here we describe how a RING finger protein, Triad3A, acts as an E3 ubiquitin-protein ligase and enhances ubiquitination and proteolytic degradation of some TLRs. Triad3A overexpression promoted substantial degradation of TLR4 and TLR9 with a concomitant decrease in signaling, but did not affect TLR2 expression or signaling.	SIGNOR-271505
Q99626	Q12864	1	transcriptional regulation	up-regulates quantity by expression	0.406	The present study aims to identify the transcription factors which interact and regulate CDH17 promoter activity that might contribute to the up-regulation of CDH17 gene in human HCC\|we identified hepatic nuclear factor 1α (HNF1α) and caudal-related homeobox 2 (CDX2) binding sites at the proximal promoter region which modulate the CDH17 promoter activities in two HCC cell lines (Hep3B and MHCC97L)	SIGNOR-253963
P05164	P02647	1	oxidation	down-regulates activity	0.406	When apolipoprotein A-I (apoA-I), the major HDL protein, was oxidized by MPO, its ability to promote cellular cholesterol efflux by ABCA1 was impaired. Moreover, oxidized apoA-I was unable to activate lecithin:cholesterol acyltransferase (LCAT), which rapidly converts free cholesterol to cholesteryl ester, a critical step in HDL maturation	SIGNOR-252102
Q92913	Q9UQD0	1	binding	down-regulates activity	0.406	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-253411
Q13950	Q92793	1	binding	up-regulates	0.406	Mechanistic analysis revealed that the tak1-mkk3/6-p38 mapk axis phosphory-lated runx2, promoting its association with the coac-tivator creb-binding protein (cbp), which is re-quired to regulate osteoblast genetic programs.	SIGNOR-166170
Q13554	P42224	1	phosphorylation	up-regulates	0.406	All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below).	SIGNOR-154771
O94955	P24864	1	binding	down-regulates quantity by destabilization	0.406	Here we show that RhoBTB3, a Golgi-associated, Rho-related ATPase, regulates the S/G2 transition of the cell cycle by targeting cyclin E for ubiquitylation. Depletion of RhoBTB3 arrested cells in S phase, triggered Golgi fragmentation, and elevated cyclin E levels. On the Golgi, RhoBTB3 bound cyclin E as part of a Cullin3 (CUL3)-dependent RING-E3 ubiquitin ligase complex comprised of RhoBTB3, CUL3, and RBX1.	SIGNOR-272131
P49841	P56693	1	phosphorylation	down-regulates quantity	0.406	Besides, GSK3\u03b2 phosphorylates SOX10 at CPD domain and facilitates Fbxw7\u03b1-mediated SOX10 degradation.\|Besides, GSK3beta phosphorylates SOX10 at CPD domain and facilitates Fbxw7alpha mediated SOX10 degradation.	SIGNOR-279617
P12931	Q00610	1	phosphorylation	up-regulates	0.406	Egf-mediated clathrin phosphorylation is followed by clathrin redistribution to the cell periphery and is the product of downstream activation of src kinase by egf receptor (egfr) signaling	SIGNOR-65714
O14965	P40337	1	phosphorylation	down-regulates quantity by destabilization	0.406	Conversely, AURKA can phosphorylate VHL at serine 72, a priming phosphorylation for GSK3beta, which regulates VHL 's role in microtubule stability.	SIGNOR-279800
P28482	P36956	1	phosphorylation	up-regulates	0.406	Map kinases erk1/2 phosphorylate sterol regulatory element-binding protein (srebp)-1a at serine 117 in vitro. mutation of serine 117 to alanine abolished erk2-mediated phosphorylation in vitro and the map kinase-related transcriptional activation of srebp-1a by insulin and platelet-derived growth factor in vivo.	SIGNOR-80092
Q9Y6B2	Q92793	1	binding	down-regulates activity	0.406	Here, we show that EID-1 is a potent inhibitor of differentiation and link this activity to its ability to inhibit p300 (and the highly related molecule, CREB-binding protein, or CBP) histone acetylation activity.	SIGNOR-253380
P49840	P01106	1	phosphorylation	down-regulates quantity by destabilization	0.406	Similar to c-myc, similar to c-myc, we report here that phosphorylation of c-jun by gsk3 creates a high-affinity binding site for the e3 ligase fbw7, which targets c-jun for polyubiquitination and proteasomal degradation.	SIGNOR-138596
Q13148	P09651	1	post transcriptional regulation	up-regulates	0.406	TDP-43 regulates the alternative splicing of hnRNP A1 to yield an aggregation-prone variant in amyotrophic lateral sclerosis	SIGNOR-262824
P25101	P63096	1	binding	up-regulates activity	0.406	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-257052
Q99942	Q9Y4P1	1	ubiquitination	down-regulates quantity by destabilization	0.405	These results substantiate the notion that RNF5 negatively regulates ATG4B availability with concomitant effect on LC3 processing and autophagy under normal growth conditions.\|These results suggest that RNF5 directly induces ATG4B ubiquitination.	SIGNOR-278664
P17612	P10276	1	phosphorylation	down-regulates activity	0.405	Mutagenesis of serine 219 (S219) and S369 at the PKA sites on RARA to either double alanines or double glutamic acids showed that both PKA sites are important for RARA activity.	SIGNOR-276281
P31749	Q00613	1	phosphorylation	up-regulates activity	0.405	Mass spectrometry showed that AKT1 also phosphorylated HSF1 at T142, S230 and T527 in addition to S326, whereas the other kinases did not. Subsequent investigation revealed that phosphorylation at T142 is necessary for HSF1 trimerization and that S230, S326 and T527 are required for HSF1 gene transactivation and recruitment of TFIIB and CDK9.	SIGNOR-277579
P06493	P22314	1	phosphorylation	up-regulates	0.405	Ubiquitin-activating enzyme, e1, is phosphorylated in mammalian cells by the protein kinase cdc2. Each serine residue was independently mutated to an alanine and analyzed by two-dimensional electrophoresis;only serine 4 was phosphorylated. Disruption of the basic amino acids within the nls resulted in loss of exclusive nuclear localization and a 90-95% decrease in the phosphorylation of ha1-e1	SIGNOR-31157
Q9Y271	P30679	1	binding	up-regulates activity	0.405	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-257225
P27361	P41182	1	phosphorylation	down-regulates	0.405	Here we show that antigen receptor activation leads to bcl-6 phosphorylation by mitogen-activated protein kinase (mapk). Phosphorylation, in turn, targets bcl-6 for rapid degradation by the ubiquitin/proteasome pathway.	SIGNOR-58493
Q14980	P68371	1	binding	up-regulates	0.405	Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.	SIGNOR-117078
P42574	P49810	1	cleavage	up-regulates activity	0.405	In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329.	SIGNOR-261743
Q16236	P00390	1	transcriptional regulation	up-regulates quantity by expression	0.405	NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulation is implicated in conferring resistance to ferroptosis across various contexts, including chemotherapy and radiation therapy	SIGNOR-279871
P17612	P35240	1	phosphorylation	up-regulates	0.405	Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth,	SIGNOR-159840
Q09472	Q15797	1	binding	up-regulates	0.405	Thus, Ski/SnoN represses TGFβ signaling by multiple mechanisms. In addition to recruitment of a transcriptional repressor complex and dissociation of the transcriptional coactivator p300/CBP from the Smads	SIGNOR-95462
P78347	O60341	1	relocalization	up-regulates activity	0.405	Moreover, the inhibitory effect of TFII-I on transcription is mediated by its ability to recruit corepressor complexes, including histone deacetylase 3 (HDAC3) (25, 133), histone H3K4-specific demethylase LSD1 (48), and components of the polycomb repressor complex	SIGNOR-268540
Q05086	P54727	1	polyubiquitination	down-regulates quantity by destabilization	0.405	Here we report the identification of HHR23A, one of the human homologues of the yeast DNA repair protein Rad23, as an E6-independent target of E6AP. E6AP-mediated ubiquitination and degradation of HHR23A and HHR23B.	SIGNOR-272551
O96017	Q13972	1	phosphorylation	down-regulates	0.405	During interphase, cdc25 is inhibited by ser287 phosphorylation (xenopus cdc25;ser 216 in human cdc25c) and this inhibitory phosphorylation is maintained by dna-responsive checkpoints / s287 is targeted by many kinases, including chk1, chk2, ctak-1, pka, p38 and mapkap kinase-2 suggesting that phosphorylation of this site may integrate multiple signaling inputs.	SIGNOR-150843
Q15788	P42229	1	binding	up-regulates	0.405	Ncoa-1/src-1 is an essential coactivator of stat5 that binds to the fdl motif in the alpha-helical region of the stat5 transactivation domain.	SIGNOR-100258
P17612	P04626	1	phosphorylation	up-regulates	0.405	Pka directly phosphorylated erbb2 on thr-686, a highly conserved intracellular regulatory site that was required for the pka-mediated synergistic enhancement of neuregulin-induced erbb2-erbb3 activation and proliferation in scs.	SIGNOR-181191
Q16539	P78536	1	phosphorylation	up-regulates activity	0.405	We show that p38 MAP kinase, which is activated in response to inflammatory or stress signals, directly activates TACE, a membrane-associated metalloprotease that is also known as ADAM17 and effects shedding in response to growth factors and Erk MAP kinase activation. p38alpha MAP kinase interacts with the cytoplasmic domain of TACE and phosphorylates it on Thr(735), which is required for TACE-mediated ectodomain shedding	SIGNOR-163970
Q15139	Q9UBF8	1	phosphorylation	up-regulates	0.405	Binding of 14-3-3 proteins to pi4kiiibeta involved the pkd phosphorylation site ser294, evident from reduced 14-3-3 binding to a s294a pi4kiiibeta mutant. Phospho-specific binding of 14-3-3 proteins to phosphatidylinositol 4-kinase iii beta protects from dephosphorylation and stabilizes lipid kinase activity.	SIGNOR-148876
P43250	O14745	1	phosphorylation	down-regulates activity	0.405	GRK6A phosphorylates NHERF on Ser289, the primary site of constitutive phosphorylation of NHERF in HEK-293 cells. The interaction of NHERF and NHE3 is mediated by the region of NHERF encompassing the second PDZ domain and the tail (25), and it is therefore reasonable that phosphorylation of the serine-rich stretch in the center of this region (including Ser289) might affect the physical interaction of NHERF with NHE3.	SIGNOR-251214
Q9H4L5	P10301	1	binding	down-regulates activity	0.405	We show that ORP3 interacts with R-Ras, a small GTPase regulating cell adhesion, spreading and migration. Gene silencing of ORP3 in HEK293 cells results in altered organization of the actin cytoskeleton, impaired cell-cell adhesion, enhanced cell spreading and an increase of beta1 integrin activity--effects similar to those of constitutively active R-Ras(38V).	SIGNOR-277221
P06493	Q09472	1	phosphorylation	down-regulates quantity by destabilization	0.404	In this study, we found that p300 was highly phosphorylated and its level was decreased during mitosis and tumorigenesis. In vitro and in vivo experiments aimed showed that cyclin-dependent kinase 1 (CDK1) and ERK1/2 phosphorylated p300 on Ser1038 and Ser2039. Mutations of Ser1038 and Ser2039 increased p300 protein stability and levels.	SIGNOR-276457
Q9H244	P63096	1	binding	up-regulates activity	0.404	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-256712
Q9H244	P08754	1	binding	up-regulates activity	0.404	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-256855
P19474	Q13501	1	ubiquitination	down-regulates activity	0.404	TRIM21 directly ubiquitylates p62 at residue K7 to inhibit its oligomerization and sequestration function.\|TRIM21 negatively regulates p62 mediated sequestration of Keap1 and antioxidant response.	SIGNOR-278602
O75688	O14920	1	dephosphorylation	down-regulates activity	0.404	PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha-induced IKKbeta-NF-kappaB activation\|Overexpression of PPM1A or PPM1B results in dephosphorylation of IKKbeta at Ser177 and Ser181 and termination of IKKbeta-induced NF-kappaB activation.	SIGNOR-248343
P63000	Q13464	1	binding	up-regulates activity	0.404	Although there are other activators of PCP, Wnt5a can activate the PCP pathway by forming a complex with Fzd and Ror2 receptors, activating DVL, which in turn activates Rho-family small GTPases, including RhoA and Rac, and their downstream effectors, Rho-associated protein kinase (ROCK), the actin-binding protein, Filamin A and c-Jun N-terminal protein kinase (JNK)	SIGNOR-258972
Q14980	P07437	1	binding	up-regulates	0.404	Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.	SIGNOR-116900
Q8IXL6	P23327	1	phosphorylation	up-regulates activity	0.404	Here, we demonstrate that family with sequence similarity 20C (Fam20C), a recently characterized protein kinase in the secretory pathway, phosphorylates HRC on Ser96. HRC Ser96 phosphorylation was confirmed in cells and human hearts.The pSer96-HRC binds tighter to triadin than S96A-HRC, which cannot be phosphorylated. Conversely, S96A-HRC or unphosphorylated Ser96-HRC binds tighter to SERCA2a. This suggests that Ser96-HRC phosphorylation (P) regulates HRC’s interactions with the major SR Ca-cycling proteins.	SIGNOR-273639
O15552	P30679	1	binding	up-regulates activity	0.404	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-257276
Q8NBJ5	P02461	1	glycosylation	up-regulates activity	0.404	Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.	SIGNOR-261154

Q96RI0

Q14344

1

binding

up-regulates

0.408

Upon proteolysis, the newly formed n terminus acts as a tethered ligand that activates the receptor and initiates signaling cascades through multiple g proteins (galfaq, galfai, and galfa12/13)

SIGNOR-196015

Q96J02

P17275

1

polyubiquitination

down-regulates quantity by destabilization

0.408

Itch promotes Ub conjugation to JunB Molecularly, Itch associated with and induced ubiquitination of JunB, a transcription factor that is involved in TH2 differentiation. However, in Itch−/− T cells under the same conditions, degradation of JunB was markedly delayed.

SIGNOR-272619

Q13627

Q01130

1

phosphorylation

down-regulates activity

0.408

Dyrk1A inhibits SC35\u2032s activity to promote tau exon 10 inclusion.|Dyrk1A interacts with and phosphorylates SC35 and inhibits its activity to promote tau exon 10 inclusion.

SIGNOR-278307

P16144

Q01453

1

binding

up-regulates activity

0.408

PMP22 is in a complex with α6β4 integrin and laminin. PMP22 and β4 integrin are in a complex in a variety of cell types. The interaction with the integrins provides PMP22 with the ability to modulate the cell–ECM communications, as well as intracellular events. Signaling between the ECM and the intracellular compartment is essential for SC myelination, as well as cellular differentiation and motility, in general. The identification of PMP22 as a binding partner for an integrin signaling complex provides a major step toward understanding the role of this disease-linked molecule in the nervous system and in non-neural cell types.

SIGNOR-251896

Q9NPG1

P50148

1

binding

up-regulates

0.408

Gpcrs signal through four relatively small families of galfa proteins (galfas, galfai/o, galfaq, and galfa12/13), and if fzd receptors are classic gpcrs, they should signal through one of these four galfa families.

SIGNOR-122895

Q13554

Q14524

1

phosphorylation

up-regulates activity

0.408

Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate–activated protein kinase (AMPK)–dependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. | Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5

SIGNOR-275773

Q8IXH6

Q9H492

1

binding

up-regulates

0.408

Tp53inp2 is a scaffold protein that recruits lc3 and/or lc3-related proteins to the autophagosome membrane by interacting with the transmembrane protein vmp1

SIGNOR-182614

Q96CN5

Q9BV73

1

binding

up-regulates activity

0.408

Here, we show that LRRC45 is a centrosome linker that localizes at the proximal ends of the centrioles and forms fiber-like structures between them. Depletion of LRRC45 results in centrosome splitting during interphase. LRRC45 interacts with C-Nap1 and rootletin

SIGNOR-273703

P68400

P30291

1

phosphorylation

down-regulates quantity by destabilization

0.408

In the present study, we show that phosphorylation of S123 (pS123) by CDK promoted the binding of Wee1A to beta-TrCP through three independent mechanisms. S123 phosphorylation creates a PBD-binding motif and accelerates S53 phosphorylation by Plk1.

SIGNOR-276038

Q16236

P00441

1

transcriptional regulation

up-regulates quantity by expression

0.408

BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2

SIGNOR-254653

Q16539

Q8TDD2

1

phosphorylation

up-regulates activity

0.408

We therefore propose that Osterix binds to Sp1 sequences on target gene promoters and that its phosphorylation by p38 enhances recruitment of coactivators to form transcriptionally active complexes

SIGNOR-255791

Q00535

O14490

1

phosphorylation

down-regulates quantity by destabilization

0.408

Taken together, these sets of data suggest that Abeta triggers the phosphorylation of GKAP by cdk5 at the serine residues S77 and S111 that in turn are crucial for GKAP degradation.

SIGNOR-279153

Q12947

P20226

1

binding

up-regulates activity

0.408

The human forkhead protein FREAC-2 contains two functionally redundant activation domains and interacts with TBP and TFIIB.

SIGNOR-220373

Q06710

Q92911

1

transcriptional regulation

up-regulates quantity by expression

0.408

Pax8 has an essential role in thyroid organogenesis and differentiation, being the main mediator of thyroid gene transcription, including the NIS gene.

SIGNOR-251990

P35813

Q16539

1

dephosphorylation

down-regulates activity

0.408

Moreover, when expressed in mammalian cells, pp2ca inhibited the activation of the p38 and jnk cascades induced by environmental stresses. Both in vivo and in vitro observations indicated that pp2ca dephosphorylated and inactivated mapkks (mkk6 and sek1) and a mapk (p38) in the stress-responsive mapk cascades. Furthermore, a direct interaction of pp2ca and p38 was demonstrated by a co-immunoprecipitation assay

SIGNOR-59618

P41231

P30679

1

binding

up-regulates activity

0.408

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-257031

P43405

P36888

1

phosphorylation

up-regulates activity

0.407

Only two mutants, FLT3-KD (V5) Y768A and Y955A, were resistant to SYK-mediated FLT3 phosphorylation, suggesting that SYK directly phosphorylates FLT3 at sites Y768 and Y955 ( ).|SYK Enhances FLT3 WT and Mutant Activation by Phosphorylation of Residues Y768 and Y955.

SIGNOR-278431

Q9NUX5

P15927

1

binding

down-regulates activity

0.407

The current model for how telomeres repress ATR signaling proposes that POT1/TPP1 prevents the binding of RPA to the single-stranded telomeric DNA

SIGNOR-263324

P06493

Q15717

1

phosphorylation

down-regulates activity

0.407

Cdk1 inhibition promoted a cytoplasmic accumulation of HuR, while a predominately nuclear localization of HuR was observed under conditions of high Cdk1 activity.|Kim et al. further showed that Cdk1-dependent Ser-202 phosphorylation of HuR was essential for 14-3-3\u03b8 binding to HuR.

SIGNOR-279014

P08575

P29597

1

dephosphorylation

down-regulates activity

0.407

CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling|these results show that CD45 dephosphorylates functionally important tyrosine residues. It should be noted that, as with our phosphatase assays in vitro, Tyr 1022 and Tyr 1023 of JAK1, Tyr 1007 and Tyr 1008 of JAK2, and Tyr 1054 and Tyr 1055 of Tyk2 are indeed hyperphosphorylated in cd45-deficient cells

SIGNOR-248357

P12931

Q92558

1

phosphorylation

up-regulates

0.407

The wave/scar proteins regulate actin polymerisation at the leading edge of motile cells via activation of the arp2/3 complex in response to extracellular cues.Src-dependent phosphorylation of scar1 promotes its association with the arp2/3 complex

SIGNOR-142724

Q9UNW8

O95837

1

binding

up-regulates activity

0.407

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-257396

Q13255

P63092

1

binding

up-regulates activity

0.407

MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.

SIGNOR-264077

Q08881

P42680

1

phosphorylation

up-regulates

0.407

Tec family protein tyrosine kinases (tfks) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the sh3 domain via a transphosphorylation mechanism. Here, we could confirm that y223 is the only site in the btk-sh3 domain being detectably phosphorylated

SIGNOR-98090

Q8TDX7

P52732

1

phosphorylation

up-regulates activity

0.407

NEK7 regulates these processes in part through phosphorylation of the kinesin Eg5/KIF11, promoting its accumulation on microtubules in distal dendrites.

SIGNOR-273890

Q9UHD2

P31749

1

phosphorylation

up-regulates

0.407

Upon mitogen stimulation, triggering of the innate immune response, re-exposure to glucose, or oncogene activation, tbk1 is recruited to the exocyst, where it activates akt. Akt is a direct tbk1 substrate that connects tbk1 to prosurvival signaling.

SIGNOR-252608

O43561

P27986

1

binding

up-regulates activity

0.407

By substituting these tyrosine residues in LAT with phenylalanine and by utilizing phosphorylated peptides derived from these sites, we mapped the tyrosine residues in LAT required for the direct interaction and activation of Vav, p85/p110alpha and phospholipase Cgamma1 (PLCgamma1). Our results indicate that Tyr(226) and Tyr(191) are required for Vav binding, whereas Tyr(171) and Tyr(132) are necessary for association and activation of phosphoinositide 3-kinase activity and PLCgamma1 respectively.

SIGNOR-246050

Q9UNE7

Q13950

1

ubiquitination

down-regulates quantity by destabilization

0.407

Here, we show that CHIP promotes Runx2 ubiquitination and degradation and thereby negatively regulates osteoblast differentiation.

SIGNOR-278600

Q9Y448

Q8N4N8

1

relocalization

down-regulates activity

0.407

The protein astrin has been shown to remove Kif2b from kinetochores in metaphase through competitive binding of CLASP1 (Manning et al., 2010 blue right-pointing triangle). During prometaphase, Aurora B kinase activity prevents astrin from localizing to kinetochores (Manning et al., 2010 blue right-pointing triangle; Schmidt et al., 2010 blue right-pointing triangle). This permits Kif2b to localize to kinetochores to destabilize k-MT attachments to execute error correction through Plk1-dependent recruitment and activation.

SIGNOR-252053

Q13315

O15360

1

phosphorylation

up-regulates

0.407

The s1449a mutant failed to completely correct a variety of fa-associated phenotypes. The dna damage response is coordinated by phosphorylation events initiated by apical kinases atm (ataxia telangectasia mutated) and atr (atm and rad3-related), and atr is essential for proper fa pathway function. Serine 1449 is in a consensus atm/atr site

SIGNOR-182949

Q14164

O43524

1

phosphorylation

down-regulates

0.407

Ikbke phosphorylation and inhibition of foxo3a: a mechanism of ikbke oncogenic functionhere we report that ikbke regulates foxo3a through phosphorylation of foxo3a-ser644. The phosphorylation of foxo3a resulted in its degradation and nuclear-cytoplasmic translocation.

SIGNOR-202054

P10144

P11717

1

binding

up-regulates

0.407

The serine proteinase granzyme b is crucial for the rapid induction of target cell apoptosis by cytotoxic t cells. We now present evidence that this receptor is the cation-independent mannose 6-phosphate/insulin-like growth factor receptor (ci-mpr). Inhibition of the granzyme b ci-mpr interaction prevented granzyme b cell surface binding, uptake, and the induction of apoptosis.

SIGNOR-84314

P52333

O14939

1

phosphorylation

up-regulates

0.407

We identified three kinases capable of phosphorylating pld2 in vitro-epidermal growth factor receptor (egfr), jak3, and src (with jak3 reported for the first time in this study)-that phosphorylate an inhibitory, an activator, and an ambivalent (one that can yield either effect) site, respectively. Mass spectrometry analyses indicated the target of each of these kinases as y(296) for egfr, y(415) for jak3, and y(511) for src.

SIGNOR-163858

P06493

O15151

1

phosphorylation

down-regulates

0.407

Cdc2p34 phosphorylates mdmx on ser 96 in vitro. Mutation within this site (mdmx(s96a)) impairs, whereas phosphomimic substitution (mdmx(s96d)) increases the cytoplasmic localization of mdmx, suggesting that cdk2/cdc2p34 phosphorylation is required for export of mdmx from the nucleus

SIGNOR-134388

P31277

O00470

1

binding

up-regulates activity

0.407

We now show that the Hoxa-9 protein physically interacts with Meis1 proteins. Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.

SIGNOR-241229

Q99942

P49023

1

ubiquitination

down-regulates quantity

0.407

Here we demonstrate that the human homologue of RNF5 associates with the amino-terminal domain of paxillin, resulting in its ubiquitination. RNF5 requires intact RING and C-terminal domains to mediate paxillin ubiquitination. Concomitantly, RNF5 expression results in inhibition of cell motility. Via targeting of paxillin ubiquitination, which alters its localization, RNF5 emerges as a novel regulator of cell motility.

SIGNOR-271479

Q70Z35

P61586

1

guanine nucleotide exchange factor

up-regulates activity

0.406

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260570

O43293

P04637

1

phosphorylation

up-regulates

0.406

A cell-free ser(20) phosphorylation site assay was used to identify a broad range of calcium calmodulin kinase superfamily members, including chk2, chk1, dapk-1, dapk-3, drak-1, and ampk, as ser(20) kinases.Evaluation of these calcium calmodulin kinase superfamily members as candidate ser(20) kinases in vivo has shown that only chk1 or dapk-1 can stimulate p53 transactivation and induce ser(20) phosphorylation of p53.

SIGNOR-153495

Q13315

Q5XUX0

1

phosphorylation

up-regulates

0.406

We find that dna damage induced by gamma-irradiation results in increased fbxo31 levels, which requires phosphorylation of fbxo31 by the ddr-initiating kinase atm

SIGNOR-185635

Q12913

P28482

1

dephosphorylation

down-regulates

0.406

In this study we show that one of these potential targets, the erk1/2, is indeed a direct dep-1 substrate in vivo.

SIGNOR-161536

Q14653

P05231

1

transcriptional regulation

up-regulates quantity by expression

0.406

Recent reports show that in mice the microbiome, comprising commensal microorganisms that colonize body surfaces, promotes a partial and low-grade M1-like phenotype in macrophages throughout the body, including those in lymphoid organs (119, 120). This M1-like priming of macrophages induces chromatin remodeling with increased H3K4me3 marks at Ifnb, Il6, and Tnf promoters, which is associated with increased binding of NF-κB p65, IRF3, and Pol II upon cell stimulation

SIGNOR-251721

P12931

Q9UGK3

1

phosphorylation

up-regulates activity

0.406

To examine this possibility, STAP-2 was co-transfected with constitutively active tyrosine kinases in HEK-293 cells. STAP-2 was strongly phosphorylated by various tyrosine kinases, including v-Src (Fig.2 A-a), a JAK2 tyrosine kinase Tyr-22 and Tyr-322 are the major tyrosine phosphorylation sites by v-Src.

SIGNOR-247337

Q15154

Q8N4C6

1

relocalization

up-regulates

0.406

Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome

SIGNOR-95077

Q8TAS1

Q15637

1

phosphorylation

up-regulates

0.406

Sf1 is phosphorylated on serines 80 and 82 in vitro and in vivo. Kis can phosphorylate sf1f on serine 80 and 82 with a high efficiency that particularly relies on the anchoring of its uhm domain to sf1. Serine phosphorylation of a conserved ser80-pro81-ser82-pro83 motif rigidifies a long unstructured linker in the sf1 helix hairpin and slightly enhances rna binding.

SIGNOR-199797

Q16659

O60229

1

phosphorylation

up-regulates activity

0.406

The brain-specific nucleotide exchange factor kalirin-7 (Kal7) was identified as an MK5 interaction partner and substrate protein. The MK5 substrate Kal7, a Rho GEF and known activator of Rac GTPases, further contributes to PAK activation and actin filament reorganization. Thus, the coordinated phosphorylation of Borg proteins and Kal7 by ERK3 and MK5 constitute a novel signaling cascade involving feed-forward circuits, multiple GTPases, and cytoskeletal elements.

SIGNOR-263094

O15033

O43464

1

ubiquitination

down-regulates quantity by destabilization

0.406

Furthermore, the ubiquitination and degradation of SMAC, HtrA2, and ARTS were significantly enhanced in AREL1-expressing cells following apoptotic stimulation, indicating that AREL1 binds to and ubiquitinates cytosolic but not mitochondria-associated forms of IAP antagonists

SIGNOR-267669

P55085

P50148

1

binding

up-regulates activity

0.406

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-257300

P78527

P11831

1

phosphorylation

up-regulates activity

0.406

The carboxyl-terminal transcription activation domain was mapped within a 71-amino acid region that contains both DNA-PK phosphorylation sites. Amino acid substitutions that interfered with phosphorylation by DNA-PK at Ser-435/446 in GAL4-SRF fusion proteins were reduced in transactivation potency. From these data we suggest that DNA-PK phosphorylation may modulate SRF activity in vivo.

SIGNOR-248922

P35222

P15172

1

binding

up-regulates activity

0.406

Together, these results suggest that B-Cat increases MyoD binding to E box elements

SIGNOR-255653

Q06187

Q9UJV9

1

phosphorylation

up-regulates activity

0.406

The kinase and SH3/SH2 interaction domains of BTK bind, respectively, the DEAD-box domain of DDX41 and transmembrane region of STING. BTK phosphorylates DDX41, and its kinase activities are critical for STING-mediated IFN-β production. We show that Tyr364 and Tyr414 of DDX41 are critical for its recognition of AT-rich DNA and binding to STING, and tandem mass spectrometry identifies Tyr414 as the BTK phosphorylation site.

SIGNOR-266404

P17612

Q5S007

1

phosphorylation

down-regulates activity

0.406

Furthermore, our work establishes S1444 as a PKA-regulated 14-3-3 docking site.Strikingly, 14-3-3 binding to phospho-S1444 decreased LRRK2 kinase activity in vitro.

SIGNOR-237444

P45984

P55957

1

phosphorylation

up-regulates activity

0.406

(c) The phosphorylation of recombinant Bid by JNK2 (in vitro kinase assay) prevents its cleavage by caspase-8

SIGNOR-279220

O75385

Q9UGI9

1

phosphorylation

down-regulates

0.406

Ulk1/2 in turn phosphorylates all three subunits of ampk and thereby negatively regulates its activity phosphorylation of ampk by ulk1 represents a negative feedback circuit.

SIGNOR-173053

Q6IQ55

O00139

1

phosphorylation

down-regulates activity

0.406

TTBK2 phosphorylates KIF2A primarily at growing MT ends and counteracts the depolymerization activity of KIF2A

SIGNOR-260926

Q15154

Q12798

1

relocalization

up-regulates

0.406

Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome

SIGNOR-94947

Q9NWF9

Q9NR96

1

ubiquitination

down-regulates quantity by destabilization

0.406

Here we describe how a RING finger protein, Triad3A, acts as an E3 ubiquitin-protein ligase and enhances ubiquitination and proteolytic degradation of some TLRs. Triad3A overexpression promoted substantial degradation of TLR4 and TLR9 with a concomitant decrease in signaling, but did not affect TLR2 expression or signaling.

SIGNOR-271505

Q99626

Q12864

1

transcriptional regulation

up-regulates quantity by expression

0.406

The present study aims to identify the transcription factors which interact and regulate CDH17 promoter activity that might contribute to the up-regulation of CDH17 gene in human HCC|we identified hepatic nuclear factor 1α (HNF1α) and caudal-related homeobox 2 (CDX2) binding sites at the proximal promoter region which modulate the CDH17 promoter activities in two HCC cell lines (Hep3B and MHCC97L)

SIGNOR-253963

P05164

P02647

1

oxidation

down-regulates activity

0.406

When apolipoprotein A-I (apoA-I), the major HDL protein, was oxidized by MPO, its ability to promote cellular cholesterol efflux by ABCA1 was impaired. Moreover, oxidized apoA-I was unable to activate lecithin:cholesterol acyltransferase (LCAT), which rapidly converts free cholesterol to cholesteryl ester, a critical step in HDL maturation

SIGNOR-252102

Q92913

Q9UQD0

1

binding

down-regulates activity

0.406

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-253411

Q13950

Q92793

1

binding

up-regulates

0.406

Mechanistic analysis revealed that the tak1-mkk3/6-p38 mapk axis phosphory-lated runx2, promoting its association with the coac-tivator creb-binding protein (cbp), which is re-quired to regulate osteoblast genetic programs.

SIGNOR-166170

Q13554

P42224

1

phosphorylation

up-regulates

0.406

All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below).

SIGNOR-154771

O94955

P24864

1

binding

down-regulates quantity by destabilization

0.406

Here we show that RhoBTB3, a Golgi-associated, Rho-related ATPase, regulates the S/G2 transition of the cell cycle by targeting cyclin E for ubiquitylation. Depletion of RhoBTB3 arrested cells in S phase, triggered Golgi fragmentation, and elevated cyclin E levels. On the Golgi, RhoBTB3 bound cyclin E as part of a Cullin3 (CUL3)-dependent RING-E3 ubiquitin ligase complex comprised of RhoBTB3, CUL3, and RBX1.

SIGNOR-272131

P49841

P56693

1

phosphorylation

down-regulates quantity

0.406

Besides, GSK3\u03b2 phosphorylates SOX10 at CPD domain and facilitates Fbxw7\u03b1-mediated SOX10 degradation.|Besides, GSK3beta phosphorylates SOX10 at CPD domain and facilitates Fbxw7alpha mediated SOX10 degradation.

SIGNOR-279617

P12931

Q00610

1

phosphorylation

up-regulates

0.406

Egf-mediated clathrin phosphorylation is followed by clathrin redistribution to the cell periphery and is the product of downstream activation of src kinase by egf receptor (egfr) signaling

SIGNOR-65714

O14965

P40337

1

phosphorylation

down-regulates quantity by destabilization

0.406

Conversely, AURKA can phosphorylate VHL at serine 72, a priming phosphorylation for GSK3beta, which regulates VHL 's role in microtubule stability.

SIGNOR-279800

P28482

P36956

1

phosphorylation

up-regulates

0.406

Map kinases erk1/2 phosphorylate sterol regulatory element-binding protein (srebp)-1a at serine 117 in vitro. mutation of serine 117 to alanine abolished erk2-mediated phosphorylation in vitro and the map kinase-related transcriptional activation of srebp-1a by insulin and platelet-derived growth factor in vivo.

SIGNOR-80092

Q9Y6B2

Q92793

1

binding

down-regulates activity

0.406

Here, we show that EID-1 is a potent inhibitor of differentiation and link this activity to its ability to inhibit p300 (and the highly related molecule, CREB-binding protein, or CBP) histone acetylation activity.

SIGNOR-253380

P49840

P01106

1

phosphorylation

down-regulates quantity by destabilization

0.406

Similar to c-myc, similar to c-myc, we report here that phosphorylation of c-jun by gsk3 creates a high-affinity binding site for the e3 ligase fbw7, which targets c-jun for polyubiquitination and proteasomal degradation.

SIGNOR-138596

Q13148

P09651

1

post transcriptional regulation

up-regulates

0.406

TDP-43 regulates the alternative splicing of hnRNP A1 to yield an aggregation-prone variant in amyotrophic lateral sclerosis

SIGNOR-262824

P25101

P63096

1

binding

up-regulates activity

0.406

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-257052

Q99942

Q9Y4P1

1

ubiquitination

down-regulates quantity by destabilization

0.405

These results substantiate the notion that RNF5 negatively regulates ATG4B availability with concomitant effect on LC3 processing and autophagy under normal growth conditions.|These results suggest that RNF5 directly induces ATG4B ubiquitination.

SIGNOR-278664

P17612

P10276

1

phosphorylation

down-regulates activity

0.405

Mutagenesis of serine 219 (S219) and S369 at the PKA sites on RARA to either double alanines or double glutamic acids showed that both PKA sites are important for RARA activity.

SIGNOR-276281

P31749

Q00613

1

phosphorylation

up-regulates activity

0.405

Mass spectrometry showed that AKT1 also phosphorylated HSF1 at T142, S230 and T527 in addition to S326, whereas the other kinases did not. Subsequent investigation revealed that phosphorylation at T142 is necessary for HSF1 trimerization and that S230, S326 and T527 are required for HSF1 gene transactivation and recruitment of TFIIB and CDK9.

SIGNOR-277579

P06493

P22314

1

phosphorylation

up-regulates

0.405

Ubiquitin-activating enzyme, e1, is phosphorylated in mammalian cells by the protein kinase cdc2. Each serine residue was independently mutated to an alanine and analyzed by two-dimensional electrophoresis;only serine 4 was phosphorylated. Disruption of the basic amino acids within the nls resulted in loss of exclusive nuclear localization and a 90-95% decrease in the phosphorylation of ha1-e1

SIGNOR-31157

Q9Y271

P30679

1

binding

up-regulates activity

0.405

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-257225

P27361

P41182

1

phosphorylation

down-regulates

0.405

Here we show that antigen receptor activation leads to bcl-6 phosphorylation by mitogen-activated protein kinase (mapk). Phosphorylation, in turn, targets bcl-6 for rapid degradation by the ubiquitin/proteasome pathway.

SIGNOR-58493

Q14980

P68371

1

binding

up-regulates

0.405

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

SIGNOR-117078

P42574

P49810

1

cleavage

up-regulates activity

0.405

In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329.

SIGNOR-261743

Q16236

P00390

1

transcriptional regulation

up-regulates quantity by expression

0.405

NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulation is implicated in conferring resistance to ferroptosis across various contexts, including chemotherapy and radiation therapy

SIGNOR-279871

P17612

P35240

1

phosphorylation

up-regulates

0.405

Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth,

SIGNOR-159840

Q09472

Q15797

1

binding

up-regulates

0.405

Thus, Ski/SnoN represses TGFβ signaling by multiple mechanisms. In addition to recruitment of a transcriptional repressor complex and dissociation of the transcriptional coactivator p300/CBP from the Smads

SIGNOR-95462

P78347

O60341

1

relocalization

up-regulates activity

0.405

Moreover, the inhibitory effect of TFII-I on transcription is mediated by its ability to recruit corepressor complexes, including histone deacetylase 3 (HDAC3) (25, 133), histone H3K4-specific demethylase LSD1 (48), and components of the polycomb repressor complex

SIGNOR-268540

Q05086

P54727

1

polyubiquitination

down-regulates quantity by destabilization

0.405

Here we report the identification of HHR23A, one of the human homologues of the yeast DNA repair protein Rad23, as an E6-independent target of E6AP. E6AP-mediated ubiquitination and degradation of HHR23A and HHR23B.

SIGNOR-272551

O96017

Q13972

1

phosphorylation

down-regulates

0.405

During interphase, cdc25 is inhibited by ser287 phosphorylation (xenopus cdc25;ser 216 in human cdc25c) and this inhibitory phosphorylation is maintained by dna-responsive checkpoints / s287 is targeted by many kinases, including chk1, chk2, ctak-1, pka, p38 and mapkap kinase-2 suggesting that phosphorylation of this site may integrate multiple signaling inputs.

SIGNOR-150843

Q15788

P42229

1

binding

up-regulates

0.405

Ncoa-1/src-1 is an essential coactivator of stat5 that binds to the fdl motif in the alpha-helical region of the stat5 transactivation domain.

SIGNOR-100258

P17612

P04626

1

phosphorylation

up-regulates

0.405

Pka directly phosphorylated erbb2 on thr-686, a highly conserved intracellular regulatory site that was required for the pka-mediated synergistic enhancement of neuregulin-induced erbb2-erbb3 activation and proliferation in scs.

SIGNOR-181191

Q16539

P78536

1

phosphorylation

up-regulates activity

0.405

We show that p38 MAP kinase, which is activated in response to inflammatory or stress signals, directly activates TACE, a membrane-associated metalloprotease that is also known as ADAM17 and effects shedding in response to growth factors and Erk MAP kinase activation. p38alpha MAP kinase interacts with the cytoplasmic domain of TACE and phosphorylates it on Thr(735), which is required for TACE-mediated ectodomain shedding

SIGNOR-163970

Q15139

Q9UBF8

1

phosphorylation

up-regulates

0.405

Binding of 14-3-3 proteins to pi4kiiibeta involved the pkd phosphorylation site ser294, evident from reduced 14-3-3 binding to a s294a pi4kiiibeta mutant. Phospho-specific binding of 14-3-3 proteins to phosphatidylinositol 4-kinase iii beta protects from dephosphorylation and stabilizes lipid kinase activity.

SIGNOR-148876

P43250

O14745

1

phosphorylation

down-regulates activity

0.405

GRK6A phosphorylates NHERF on Ser289, the primary site of constitutive phosphorylation of NHERF in HEK-293 cells. The interaction of NHERF and NHE3 is mediated by the region of NHERF encompassing the second PDZ domain and the tail (25), and it is therefore reasonable that phosphorylation of the serine-rich stretch in the center of this region (including Ser289) might affect the physical interaction of NHERF with NHE3.

SIGNOR-251214

Q9H4L5

P10301

1

binding

down-regulates activity

0.405

We show that ORP3 interacts with R-Ras, a small GTPase regulating cell adhesion, spreading and migration. Gene silencing of ORP3 in HEK293 cells results in altered organization of the actin cytoskeleton, impaired cell-cell adhesion, enhanced cell spreading and an increase of beta1 integrin activity--effects similar to those of constitutively active R-Ras(38V).

SIGNOR-277221

P06493

Q09472

1

phosphorylation

down-regulates quantity by destabilization

0.404

In this study, we found that p300 was highly phosphorylated and its level was decreased during mitosis and tumorigenesis. In vitro and in vivo experiments aimed showed that cyclin-dependent kinase 1 (CDK1) and ERK1/2 phosphorylated p300 on Ser1038 and Ser2039. Mutations of Ser1038 and Ser2039 increased p300 protein stability and levels.

SIGNOR-276457

Q9H244

P63096

1

binding

up-regulates activity

0.404

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-256712

Q9H244

P08754

1

binding

up-regulates activity

0.404

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-256855

P19474

Q13501

1

ubiquitination

down-regulates activity

0.404

TRIM21 directly ubiquitylates p62 at residue K7 to inhibit its oligomerization and sequestration function.|TRIM21 negatively regulates p62 mediated sequestration of Keap1 and antioxidant response.

SIGNOR-278602

O75688

O14920

1

dephosphorylation

down-regulates activity

0.404

PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha-induced IKKbeta-NF-kappaB activation|Overexpression of PPM1A or PPM1B results in dephosphorylation of IKKbeta at Ser177 and Ser181 and termination of IKKbeta-induced NF-kappaB activation.

SIGNOR-248343

P63000

Q13464

1

binding

up-regulates activity

0.404

Although there are other activators of PCP, Wnt5a can activate the PCP pathway by forming a complex with Fzd and Ror2 receptors, activating DVL, which in turn activates Rho-family small GTPases, including RhoA and Rac, and their downstream effectors, Rho-associated protein kinase (ROCK), the actin-binding protein, Filamin A and c-Jun N-terminal protein kinase (JNK)

SIGNOR-258972

Q14980

P07437

1

binding

up-regulates

0.404

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

SIGNOR-116900

Q8IXL6

P23327

1

phosphorylation

up-regulates activity

0.404

Here, we demonstrate that family with sequence similarity 20C (Fam20C), a recently characterized protein kinase in the secretory pathway, phosphorylates HRC on Ser96. HRC Ser96 phosphorylation was confirmed in cells and human hearts.The pSer96-HRC binds tighter to triadin than S96A-HRC, which cannot be phosphorylated. Conversely, S96A-HRC or unphosphorylated Ser96-HRC binds tighter to SERCA2a. This suggests that Ser96-HRC phosphorylation (P) regulates HRC’s interactions with the major SR Ca-cycling proteins.

SIGNOR-273639

O15552

P30679

1

binding

up-regulates activity

0.404

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-257276

Q8NBJ5

P02461

1

glycosylation

up-regulates activity

0.404

Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.

SIGNOR-261154