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
P12931	P35222	1	phosphorylation	down-regulates activity	0.761	beta-catenin is a good substrate of pp60c- srctyrosine kinase in vitro;this kinase modifies specifically tyr-86 and tyr-654although consistently detected, this negative effect of tyr-86 phosphorylation on tbp binding was clearly less important than the positive effect observed after tyr-654 phosphorylation.	SIGNOR-106458
A6ND36	Q9Y5K6	2	binding	up-regulates activity	0.346	PAWS1 interacts in a dynamic fashion with the actin/cytoskeletal regulator CD2AP at lamellae\|Loss of PAWS1 causes severe defects in F-actin organization and distribution as well as in lamellipodial organization, resulting in impaired cell migration.	SIGNOR-264768
Q16654	P11498	1	phosphorylation	down-regulates activity	0.373	PDK4 phosphorylates and inhibits the pyruvate dehydrogenase complex (PDC) which catalyzes the conversion of pyruvate to acetyl-CoA in the glucose oxidation pathway.	SIGNOR-278974
Q6T4R5	Q07157	2	binding	up-regulates activity	0.2	NHS-A is a novel interactor of ZO-1 and is expected to have a role at tight junctions. Its recruitment to these junctions is dependent upon their assembly.	SIGNOR-253567
Q13393	Q15382	2	binding	up-regulates	0.537	Rheb binds and activates pld1 in vitro in a gtp-dependent manner, strongly suggesting that pld1 is a bona fide effector for rheb.	SIGNOR-178892
P19086	P14416	2	binding	up-regulates activity	0.391	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-257096
Q15831	Q9P0L2	1	phosphorylation	up-regulates	0.41	Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold	SIGNOR-122545
O00429	Q5S007	0	phosphorylation	up-regulates activity	0.568	LRRK2 G2019S directly bound to and phosphorylated Drp1 at Threonine595, whereas P110 treatment abolished this phosphorylation.Threonine595 phosphorylation of Drp1 by LRRK2 G2019S is required for Drp1-mediated mitochondrial fragmentation and excessive autophagy	SIGNOR-276495
P45985	Q13233	0	phosphorylation	up-regulates activity	0.729	The gck-ctd-mekk1 interaction is sufficiently stable to support mekk1 s phosphorylation of its substrate, sek1	SIGNOR-236380
Q9NW38	Q9BXW9	1	ubiquitination	up-regulates activity	0.9	Thus, eight of the nine components of the FA core complex are FA proteins (FANC‐A, B, C, E, F, G, L, and M). Furthermore, two of the newly discovered FA proteins have enzymatic activities: FANCL is a ubiquitin ligase essential for FANCD2 monoubiquitination in vivo	SIGNOR-263250
A8MYZ6	Q14938	0	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268887
P24941	P28482	0	phosphorylation	up-regulates	0.497	In addition to its role in stimulating cyclin d1 expression and nuclear translocation of cdk2, erk regulates thr-160 phosphorylation of cdk2-cyclin e.	SIGNOR-94003
P10914	Q03001	1	transcriptional regulation	down-regulates quantity by repression	0.2	Transient transfection studies with BPAG1 promoter-luciferase reporter gene plasmids and IRF1 and IRF2 expression plasmids revealed that IRF1 and IRF2 directly down-regulated BPAG1 gene transcription in cultured normal human epidermal keratinocytes.	SIGNOR-254492
P63096	P08173	2	binding	up-regulates activity	0.454	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-256686
P42684	Q14689	2	binding	up-regulates activity	0.2	Here, using cultured hippocampal neurons pooled from both sexes of mice, we provide evidence that binding to cortactin tethers Abl2 in spines, where Abl2 and cortactin maintain the small pool of stable actin required for dendritic spine stability.	SIGNOR-266593
P25963	Q9HC78	0	transcriptional regulation	down-regulates quantity by repression	0.259	ChIP and next generation high-throughput DNA sequencing assay showed that ZBTB20 specifically bound to IκBα gene promoter (+1 to +60 region) after TLR activation. ZBTB20 could inhibit IκBα gene transcription, govern IκBα protein expression, and then promote NF-κB activation. Therefore, transcriptional repressor ZBTB20 is needed to promote full activation of TLR signaling and TLR-triggered innate immune response by selectively suppressing the suppressor IκBα gene transcription.	SIGNOR-266868
Q03431	P01270	2	binding	up-regulates	0.772	Here we show that binding of pth to its receptor pth1r induced association of lrp6, a coreceptor of wnt, with pth1r. The formation of the ternary complex containing pth, pth1r, and lrp6 promoted rapid phosphorylation of lrp6, which resulted in the recruitment of axin to lrp6, and stabilization of beta-catenin.	SIGNOR-182039
P14618	Q9P1W9	0	phosphorylation	up-regulates quantity by stabilization	0.37	Here, we identified the protein-serine/threonine kinase PIM2, a known oncogene, as a novel binding partner of PKM2. The interaction between PIM2 and PKM2 was confirmed by multiple biochemical approaches in vitro and in cultured cells. Importantly, we found that PIM2 could directly phosphorylate PKM2 on the Thr-454 residue, resulting in an increase of PKM2 protein levels. Compared with wild type, PKM2 with the phosphorylation-defective mutation displayed a reduced effect on glycolysis	SIGNOR-267472
P00519	Q06830	1	phosphorylation	down-regulates activity	0.387	Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. To determine whether Prxs are phosphorylated, we subjected recombinant human PrxI and II to an in vitro kinase assay with two nonreceptor PTKs, Lck and Abl, in the presence of [γ-32P]ATP. Both PTKs phosphorylated PrxI and PrxII. Phosphorylation of the wild-type protein was detected, whereas that of the Y194F mutant was not (Figure 1B), indicating that Tyr194 is the only site of tyrosine phosphorylation.	SIGNOR-276278
P09467	Q16665	2	binding	down-regulates activity	0.326	FBP1, but not FBP2, suppresses HIF-1a activity by directly binding to its inhibitory domain.	SIGNOR-267590
O96017	P10721	1	phosphorylation	up-regulates	0.286	In this report, we characterize the binding of sh2(chk) to specific phosphotyrosine sites on the c-kit protein sequence. the sh2(chk) binding to the two sites is direct and not through phosphorylated intermediates such as fyn or shc. this indicates that chk binds to the same site on c-kit to which fyn binds, possibly bringing the two into proximity on associated c-kit subunits and leading to the down-regulation of fyn by chk.	SIGNOR-197281
O96001	Q13976	0	phosphorylation	up-regulates	0.656	Recombinant human G-substrate was phosphorylated efficiently by cGMP-dependent protein kinase exclusively at Thr residues, and it was recognized by antibodies specific for rabbit phospho-G-substrate. The amino acid sequences surrounding the sites of phosphorylation in G-substrate are related to those around Thr-34 and Thr-35 of the dopamine- and cAMP-regulated phosphoprotein DARPP-32 and inhibitor-1, respectively, two potent inhibitors of protein phosphatase 1.	SIGNOR-263148
Q9NQS5	P19086	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-257099
Q8N9L9	P0DMV8	2	binding	down-regulates quantity by destabilization	0.2	HSPA1A binds unphosphorylated ACOT4 and promotes its degradation	SIGNOR-271819
P06239	P27986	1	phosphorylation	down-regulates activity	0.623	the regulatory p85 subunit of phosphatidylinositol 3-kinase is phosphorylated on tyrosine residues. We report that this phosphorylation event is readily catalyzed by the Abl and Lck protein-tyrosine kinases in vitro, by Bcr-Abl or a catalytically activated Lck-Y505F in co-transfected COS cells. we have mapped a major phosphorylation site to Tyr-688 in the C-terminal SH2 domain of p85. Tyrosine phosphorylation of p85 in vitro or in vivo was not associated with detectable change in the enzymatic activity of the phosphatidylinositol 3-kinase heterodimer, but correlated with a strong reduction in the binding of some, but not all, phosphoproteins to the SH2 domains of p85.	SIGNOR-251383
P30291	Q8IY84	0	phosphorylation	down-regulates activity	0.48	Furthermore, purified bacterially produced Nim1 kinase directly phosphorylates and inactivates Wee1 in vitro.\|Phosphorylation and inactivation of the mitotic inhibitor Wee1 by the nim1 and cdr1 kinase.	SIGNOR-279238
Q13547	O15379	2	binding	up-regulates	0.533	Furthermore, smad7 caused hdac-1 bind to e2f-1 to form a ternary complex on chromosomal dna containing an e2f-binding motif and leading to repression in the activity of the e2f target genes.	SIGNOR-199964
Q13451	Q9NZQ7	1	catalytic activity	up-regulates quantity by expression	0.2	FKBP51s upregulated PD-L1 expression on the plasma membrane by catalysing the protein folding required for subsequent glycosylation. Inhibition of FKBP51s isomerase activity by SAFit decreased PD-L1 levels	SIGNOR-274973
P41597	O60674	0	phosphorylation	up-regulates activity	0.605	JAK2 phosphorylates CCR2 at the Tyr139 position and promotes JAK2/STAT3 complex association to the receptor.	SIGNOR-251345
P20645	O60664	0	relocalization	up-regulates activity	0.73	TIP47 is present in cytosol and on endosomes and is required for MPR transport from endosomes to the trans-Golgi network in vitro and in vivo. TIP47 recognizes a phenylalanine/tryptophan signal in the tail of the cation-dependent MPR that is essential for its proper sorting within the endosomal pathway. These data suggest that TIP47 binds MPR cytoplasmic domains and facilitates their collection into transport vesicles destined for the Golgi.	SIGNOR-253093
O43865	Q9Y6R1	2	binding	up-regulates activity	0.671	IRBIT opposed the effects of WNKs and SPAK by recruiting PP1 to the complex to dephosphorylate CFTR and NBCe1-B, restoring their cell surface expression, in addition to stimulating their activities.	SIGNOR-263135
Q16695	Q15652	0	demethylation	down-regulates activity	0.2	We now determine that JMJD1C is recruited by USF-1 to various lipogenic genes for H3K9 demethylation to enhance chromatin accessibility in the fed state.	SIGNOR-265170
P10415	O75030	0	transcriptional regulation	up-regulates quantity by expression	0.475	MITF directly occupies the BCL2 promoter in vivo and this suggest that BCL2 may be a direct transcriptional target of MITF	SIGNOR-249618
Q99684	P17947	2	binding	down-regulates activity	0.594	Our data demonstrate that GFI-1 physically interacts with PU.1, repressing PU.1-dependent transcription. This repression is functionally significant, as GFI-1 blocked PU.1-induced macrophage differentiation of a multipotential hematopoietic progenitor cell line.	SIGNOR-256043
P35269	P35269	2	phosphorylation	down-regulates	0.2	We show that tfiifalpha possesses a serine/threonine kinase activity, allowing an autophosphorylation of the two residues at position serine 385 and threonine 389. Mutation analysis strongly suggests that autophosphorylation of both sites regulates the transcription elongation process.	SIGNOR-69767
Q13526	Q14653	2	binding	down-regulates quantity by destabilization	0.643	Here we report that activation of IRF3 is negatively regulated by the peptidyl-prolyl isomerase Pin1. After stimulation by double-stranded RNA, induced phosphorylation of the Ser339–Pro340 motif of IRF3 led to its interaction with Pin1 and finally polyubiquitination and then proteasome-dependent degradation of IRF3. Suppression of Pin1 by RNA interference or genetic deletion resulted in enhanced IRF-3-dependent production of interferon-beta, with consequent reduction of virus replication.	SIGNOR-252256
P53350	O14757	0	phosphorylation	down-regulates activity	0.314	Chk1 directly phosphorylates Plk1 to disturb its interaction with Sgo1.	SIGNOR-277914
P63096	P35346	2	binding	up-regulates activity	0.496	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-256690
P49841	Q9Y2X9	1	phosphorylation	down-regulates quantity by destabilization	0.2	GSK-3beta phosphorylation-dependent degradation of ZNF281 by beta-TrCP2 suppresses colorectal cancer progression\|	SIGNOR-264890
P49674	P35222	1	phosphorylation	down-regulates activity	0.657	Using mass spectrometry and phosphopeptide-specific antibodies, we show that a complex of axin and casein kinase I (CKI) induces Beta-catenin phosphorylation at a single site: serine 45 (S45).	SIGNOR-244102
O14920	Q99759	0	phosphorylation	up-regulates activity	0.569	Genetic analysis showed that MEKK3, which is thought to activate IKK2 through phosphorylation (Yang et al., 2001), is necessary for TNF-alpha-induced NF-kappaB activation.\|Our results also suggest that IKK2 is phosphorylated on S177 and S181 on its activation loop by MEKK3.	SIGNOR-279468
O75582	P0C0S8	1	phosphorylation	up-regulates	0.2	We found that msk1 phosphorylated histone h2a on serine 1, and mutation of serine 1 to alanine blocked the inhibition of transcription by msk1.	SIGNOR-123383
O43524	Q13131	0	phosphorylation	up-regulates activity	0.517	Phosphorylation by AMPK leads to the activtion of FOXO3 transcriptional activity without affecting FOXO3 subcellular localization.	SIGNOR-249684
P62140	O15169	1	dephosphorylation	down-regulates activity	0.2	The data suggest that PP1 controls Wnt signaling through interaction with, and regulated dephosphorylation of, axin\| Axin phosphorylation markedly enhances the binding of glycogen synthase kinase 3, leading to a more active beta-catenin destruction complex. Wnt-regulated changes in axin phosphorylation, mediated by PP1, may therefore determine beta-catenin transcriptional activity\| Four sites, S80, S82, S222, and S473, were identified to be PP1 regulated	SIGNOR-248567
Q92914	P35498	2	binding	down-regulates activity	0.259	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-253422
P17252	P48730	1	phosphorylation	up-regulates activity	0.2	In the present study we analyzed the CK1δ kinase domain for phosphorylation sites targeted by PKCα. Several phosphorylation sites were identified in vitro by initially using GST-CK1δ wild type and phosphorylation-site mutant protein fragments originating from the CK1δ kinase domain. Residues S53, T176, and S181 could finally be confirmed as targets for PKCα. Determination of kinetic parameters of full-length wild type and mutant GST-CK1δ-mediated substrate phosphorylation revealed that integrity of residue T176 is crucial for maintaining CK1δ kinase activity.	SIGNOR-277452
P27361	O60674	1	phosphorylation	down-regulates	0.523	We hypothesize that phosphorylation of ser523 in jak2 by erks 1 and/or 2 or other as-yet-unidentified kinases acts in a negative feedback manner	SIGNOR-146747
Q9UQ80	P07288	1	transcriptional regulation	down-regulates quantity by repression	0.2	Ectopic expression of ebp1, a member of the PA2G4 family, inhibits the proliferation and induces the differentiation of human breast and prostate cancer cell lines. Ebp1 inhibits transcription of E2F1 and androgen receptor regulated genes such as prostate specific antigen (PSA) through its interactions with histone deacetylases (HDACs)	SIGNOR-253662
Q86WA8	Q2T9J0	1	cleavage	down-regulates quantity by destabilization	0.66	Self-cleavage of Tysnd1 in the active oligomer most likely inactivates its protease activity. Subsequently, the cleaved products are degraded by PsLon and removed from the Tysnd1 oligomer.	SIGNOR-261054
Q16625	P05129	0	phosphorylation	up-regulates activity	0.307	Protein kinase C regulates the phosphorylation and cellular localization of occludin. Ser(338) of occludin was identified as an in vitro protein kinase C phosphorylation site using peptide mass fingerprint analysis and electrospray ionization tandem mass spectroscopy. Both the phosphorylation of occludin and its incorporation into tight junctions induced by calcium switch were markedly inhibited by the PKC inhibitor GF-109203X.	SIGNOR-249107
Q99748	P56159	2	binding	up-regulates	0.738	A receptor complex comprised of trnr1 (gdnfr alpha) and ret was recently identified and found to be capable of mediating both gdnf and ntn signaling	SIGNOR-49119
P16284	P41240	0	phosphorylation	up-regulates activity	0.55	We demonstrated that phosphorylation of PECAM-1 by Src or Csk family kinases was sufficient to trigger its association with SHP-2. Moreover, it was able to promote binding of PECAM-1 to SHP-1, a SHP-2-related protein-tyrosine phosphatase expressed in hemopoietic cells. Taken together, these findings indicated that the Src and Csk families of kinases are strong candidates for mediating tyrosine phosphorylation of PECAM-1 and triggering its association with SH2 domain-containing phosphatases under physiological circumstances.	SIGNOR-262741
P27361	Q9BRX9	2	binding	up-regulates	0.508	Morg1 specifically associates with several components of the erk pathway, including mp1, raf-1, mek, and erk, and stabilizes their assembly into an oligomeric complex.	SIGNOR-124473
Q16236	O96013	0	phosphorylation	down-regulates quantity by destabilization	0.2	PAK4 directly phosphorylated Nrf2 at T369, and it led to its nuclear export and proteasomal degradation, all of which impaired antioxidant responses in hepatocytes.	SIGNOR-277583
Q9HCU9	O43791	0	ubiquitination	down-regulates quantity	0.402	Intriguingly, BRMS1 turns out to be a potent substrate that is ubiquitinated by the Cul3-SPOP complex. Knockdown of SPOP increases the level of BRMS1 protein and represses the expression of BRMS1 repressive target genes such as OPN and uPA in breast cancer cells.	SIGNOR-268857
P07900	P29474	2	binding	up-regulates	0.76	The binding of hsp90 to enos enhances the activation of enos.	SIGNOR-57211
O00744	Q9UP38	2	binding	up-regulates	0.664	Inhibition of adipogenesis by wnt10b is likely mediated by wnt receptors, frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor-related proteins 5 and 6	SIGNOR-89134
P01106	Q06203	1	transcriptional regulation	up-regulates quantity by expression	0.2	PPAT, catalyzing the first step of purine synthesis, and DHODH, an enzyme generating uridine in the middle of the pyrimidine synthesis pathway, were validated as direct c-MYC target genes by all criteria.	SIGNOR-267381
O15524	P15498	2	binding	down-regulates quantity by destabilization	0.598	SOCS1 stimulates the polyubiquitination of VAV proteins in vivo, which was stabilized by proteasomal inhibitors. These results suggest that SOCS1 programs VAV degradation by acting as a substrate-specific recognition component of a VCB-like ubiquitin ligase complex.	SIGNOR-272559
P07949	P39905	2	binding	up-regulates	0.91	A receptor complex comprised of trnr1 (gdnfr alpha) and ret was recently identified and found to be capable of mediating both gdnf and ntn signaling	SIGNOR-49094
Q8IXL6	P07237	1	phosphorylation	up-regulates activity	0.387	The secretory pathway kinase Fam20C phosphorylates Ser357 of PDI and responds rapidly to various ER stressors. Phosphorylation of Ser357 induces an open conformation of PDI and turns it from a "foldase" into a "holdase", which is critical for preventing protein misfolding in the ER. Phosphorylated PDI also binds to the lumenal domain of IRE1α, a major UPR signal transducer, and attenuates excessive IRE1α activity.	SIGNOR-275574
P05129	P49840	1	phosphorylation	down-regulates	0.324	Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.	SIGNOR-115726
Q05086	P04637	1	ubiquitination	down-regulates quantity	0.681	E6-AP also directly ubiquitylated p53 in an in vitro ubiquitylation assay.\|Our result suggests that E6-AP not only enhances the degradation of p53 but also regulates the neuronal cell growth.	SIGNOR-278681
O95944	P12004	2	binding	down-regulates activity	0.307	NK cells play an important role in the early immune response to cancer. The NKp44 activating receptor is the only natural cytotoxicity receptor that is expressed exclusively by primate NK cells, yet its cellular ligands remain largely unknown.	SIGNOR-260043
P31273	O43541	2	binding	up-regulates activity	0.529	Smad6 interacts with hox transcription factors as part of the negative feedback circuit in the bmp signaling pathway	SIGNOR-75823
Q96GD4	Q9UKC9	2	binding	down-regulates quantity by destabilization	0.483	The SCF complex contains a catalytic core consisting of Skp1, Cullin1, and the E2 ubiquitin-conjugating (Ubc) enzyme and a F box component that acts as a receptor targeting numerous substrates via phosphodegron elicited interactions. our screening studies suggested that FBXL2 also targets Aurora B protein for ubiquitination and degradation.	SIGNOR-272097
Q9NTX7	Q9H2K2	1	ubiquitination	down-regulates quantity	0.614	We show that RNF146, tankyrase, and Axin form a protein complex, and that RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation.	SIGNOR-260005
Q14738	P17612	0	phosphorylation	up-regulates	0.2	Protein kinase a activates protein phosphatase 2a by phosphorylation of the b56delta subunit.	SIGNOR-153218
Q9Y3Z3	P06493	0	phosphorylation	down-regulates	0.492	Cyclin a2/cdk1 phosphorylates samhd1 at the threonine 592 residue both in vitro and in vivo. Phosphorylation of samhd1 thr592 correlates with loss of its ability to restrict hiv-1.	SIGNOR-201913
P68400	P54252	1	phosphorylation	up-regulates activity	0.2	Here we show that protein casein kinase 2 (CK2)-dependent phosphorylation controls the nuclear localization, aggregation and stability of ataxin-3 (ATXN3), the disease protein in spinocerebellar ataxia type 3 (SCA3). The main phosphorylation of ATXN3 in vivo thus occurred at serine residues within the three conserved UIMs.	SIGNOR-276224
P11309	Q16665	1	phosphorylation	up-regulates quantity by stabilization	0.2	PIM1 kinase directly phosphorylates HIF-1α at threonine 455, a previously uncharacterized site within its oxygen-dependent degradation domain. This phosphorylation event disrupts the ability of prolyl hydroxylases to bind and hydroxylate HIF-1α, interrupting its canonical degradation pathway and promoting constitutive transcription of HIF-1 target genes.	SIGNOR-277311
Q9UBK2	P16220	0	transcriptional regulation	up-regulates quantity by expression	0.554	CREB was found to induce expression of the gluconeogenic programme through the nuclear receptor coactivator PGC-1, which is shown here to be a direct target for CREB regulation in vivo	SIGNOR-256150
Q9UKA1	Q14203	2	binding	down-regulates quantity by destabilization	0.462	FBXL5 binds to p150(Glued)in vitro and in vivo. FBXL5 and p150(Glued) co-localize primarily in the cytoplasm with peri-nuclear enrichment in HeLa cells. Overexpression of FBXL5 promotes poly-ubiquitination of p150(Glued) and protein turnover of p150(Glued). Our findings provide a potential mechanism by which p150(Glued) protein function is regulated by SCFs.	SIGNOR-271652
Q92558	P12931	0	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
P68400	P35221	1	phosphorylation	down-regulates	0.39	We demonstrate here that egfr activation results in disruption of the complex of beta-catenin and alpha-catenin, thereby abrogating the inhibitory effect of alpha-catenin on beta-catenin transactivation via ck2alpha-dependent phosphorylation of alpha-catenin at s641.	SIGNOR-161847
Q15139	Q15276	1	phosphorylation	up-regulates activity	0.382	PKD phosphorylates Rabaptin-5 at Ser407, and this controls alphavbeta3 and alpha5beta1 integrin and EGFR recycling.	SIGNOR-278192
O14559	P63000	1	gtpase-activating protein	down-regulates activity	0.444	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-260491
P40238	Q8WWM7	2	binding	down-regulates	0.353	A2d binds to cytokine receptors mpl and epo-r. A2d is associated with these unoccupied receptorsin vivo,and stimulation with tpo or epo causes the rapid dissociation of a2d from the activated receptor.	SIGNOR-113891
Q9HC23	Q8NFJ6	2	binding	up-regulates	0.665	We have cloned two closely related receptors for pk1 and pk2. These receptors, named prokineticin receptor 1 and 2 (pkr1 and pkr2)	SIGNOR-87919
P00533	Q9UBN7	1	phosphorylation	down-regulates	0.44	A negative feedback loop consisting of egfr-mediated phosphorylation of hdac6 tyr(570) resulted in reduced deacetylase activity and increased acetylation of alpha-tubulin.	SIGNOR-162431
P19086	P24530	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-257321
Q05513	Q07812	1	phosphorylation	down-regulates activity	0.2	Protein kinase czeta abrogates the proapoptotic function of bax through phosphorylation. Overexpression of wild type or the constitutively active a119d but not the dominant negative k281w pkczeta mutant results in bax phosphorylation at serine 184.	SIGNOR-155111
P23443	O60331	1	phosphorylation	down-regulates quantity by destabilization	0.2	Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKIγ90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKIγ90 phosphorylation is essential for cell migration and invasion. These data suggest that S6K1-mediated PIPKIγ90 phosphorylation regulates cell migration and invasion by controlling PIPKIγ90 degradation.	SIGNOR-277283
O95837	P21462	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-256961
P09471	Q9H244	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-256991
O43150	Q14289	0	phosphorylation	up-regulates activity	0.525	Tyrosine phosphorylation of Pap by Pyk2 or Src kinases. We have identified a new Pyk2 binding protein designated Pap. Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. We demonstrate that Pap forms a stable complex with Pyk2 and that activation of Pyk2 leads to tyrosine phosphorylation of Pap in living cells.	SIGNOR-269704
Q9UDT6	Q7Z460	2	binding	up-regulates activity	0.594	CLIP-associating protein (CLASP) 1 and CLASP2 are mammalian microtubule (MT) plus-end binding proteins, which associate with CLIP-170 and CLIP-115.\|We demonstrate that the middle part of CLASPs binds directly to EB1 and to MTs. \| Both EB1- and cortex-binding domains of CLASP are required to promote MT stability.	SIGNOR-265092
P42224	O15111	0	phosphorylation	up-regulates activity	0.331	In addition, IKK\u03b1 also phosphorylated STAT1 in a type I IFN-independent manner [Fig 8, a dashed line (B)].	SIGNOR-279732
P04150	P49715	1	transcriptional regulation	up-regulates quantity by expression	0.455	We show that in addition, DEX-bound GR directly promotes the expression of adipogenic TFs, including C/EBPβ, Klf5, Klf9, and C/EBPα	SIGNOR-256116
P35398	O00327	1	transcriptional regulation	up-regulates quantity by expression	0.689	Direct Regulation of the NPAS2 Promoter by RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding.	SIGNOR-267982
P53004	P06213	0	phosphorylation	up-regulates activity	0.479	Human BVR (hBVR) also reduces the hemeoxygenase activity product biliverdin to bilirubin and is directly activated by insulin receptor kinase (IRK).\|in addition to Y198 in the YMKM motif, 2 other tyrosines, Y228 in the YLSF motif and Y291 in the C-terminus of the protein, are directly phosphorylated by IRK	SIGNOR-275514
P23528	Q76I76	0	dephosphorylation	up-regulates activity	0.732	Differential activities, subcellular distribution and tissue expression patterns of three members of Slingshot family phosphatases that dephosphorylate cofilin.\|Cofilin, a key regulator of actin filament dynamics, is inactivated by phosphorylation at Ser-3 by LIM-kinases and is reactivated by dephosphorylation by a family of protein phosphatases, termed Slingshot (SSH).	SIGNOR-248733
P51828	Q05655	0	phosphorylation	up-regulates activity	0.555	Immunoprecipitation data indicated that PKCdelta could bind and directly phosphorylate AC7.	SIGNOR-279258
Q9UQM7	Q86UR5	1	phosphorylation	up-regulates	0.347	Two serine residues in rim1 (ser-241 and ser-287) and one serine residue in rim2 (ser-335) were required for 14-3-3 binding. Incubation with ca2+/calmodulin-dependent protein kinase ii greatly stimulated the interaction of recombinant n-terminal rim but not the s241/287a mutant with 14-3-3,	SIGNOR-103890
Q12983	Q15382	2	binding	down-regulates	0.751	Bnip3, a hypoxia-inducible bcl-2 homology 3 domain-containing protein, directly binds rheb and inhibits the mtor pathway. Bnip3 decreases rheb gtp levels in a manner depending on the binding to rheb.	SIGNOR-158274
Q5VWQ8	P10275	2	binding	down-regulates activity	0.328	DAB2IP acts as a scaffold protein for PP2A to suppress DHT-elicited S81 phosphorylation of the AR, preventing its nuclear translocation and binding to androgen response elements. In addition, DAB2IP can compete with the AR for binding to c-Src, thus blocking the non-genomic AR pathway	SIGNOR-254758
P01189-PRO_0000024969	Q01726	2	binding	up-regulates activity	0.2	The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins	SIGNOR-268701
Q92630	P04637	1	phosphorylation	up-regulates	0.67	Here, we demonstrate that the dual-specificity tyrosine-phosphorylation-regulated kinase 2 (dyrk2) directly phosphorylates p53 at ser46. these findings indicate that dyrk2 regulates p53 to induce apoptosis in response to dna damage.	SIGNOR-153544
P28482	Q9BYB0	1	phosphorylation	down-regulates activity	0.2	Interestingly, we discovered that several kinases in the MEK and ERK2 pathway destabilize Shank3 and that genetic deletion and pharmacological inhibition of ERK2 increases Shank3 abundance in vivo.\|We also determined that phosphorylation of Shank3 by ERK2 at selective residues promotes its ubiquitination and degradation.	SIGNOR-279538
P08651	O00712	2	binding	down-regulates activity	0.362	Coexpression of NFI-B3 with other isoforms of the NFI-B, -C, and -X family, however, led to a strong reduction of transcriptional activation compared with the expression of these factors alone. NFI-B3 apparently forms heterodimers with other NFI proteins thereby interfering with their function.	SIGNOR-240880

P12931

P35222

1

phosphorylation

down-regulates activity

0.761

beta-catenin is a good substrate of pp60c- srctyrosine kinase in vitro;this kinase modifies specifically tyr-86 and tyr-654although consistently detected, this negative effect of tyr-86 phosphorylation on tbp binding was clearly less important than the positive effect observed after tyr-654 phosphorylation.

SIGNOR-106458

A6ND36

Q9Y5K6

2

binding

up-regulates activity

0.346

PAWS1 interacts in a dynamic fashion with the actin/cytoskeletal regulator CD2AP at lamellae|Loss of PAWS1 causes severe defects in F-actin organization and distribution as well as in lamellipodial organization, resulting in impaired cell migration.

SIGNOR-264768

Q16654

P11498

1

phosphorylation

down-regulates activity

0.373

PDK4 phosphorylates and inhibits the pyruvate dehydrogenase complex (PDC) which catalyzes the conversion of pyruvate to acetyl-CoA in the glucose oxidation pathway.

SIGNOR-278974

Q6T4R5

Q07157

2

binding

up-regulates activity

0.2

NHS-A is a novel interactor of ZO-1 and is expected to have a role at tight junctions. Its recruitment to these junctions is dependent upon their assembly.

SIGNOR-253567

Q13393

Q15382

2

binding

up-regulates

0.537

Rheb binds and activates pld1 in vitro in a gtp-dependent manner, strongly suggesting that pld1 is a bona fide effector for rheb.

SIGNOR-178892

P19086

P14416

2

binding

up-regulates activity

0.391

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-257096

Q15831

Q9P0L2

1

phosphorylation

up-regulates

0.41

Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold

SIGNOR-122545

O00429

Q5S007

0

phosphorylation

up-regulates activity

0.568

LRRK2 G2019S directly bound to and phosphorylated Drp1 at Threonine595, whereas P110 treatment abolished this phosphorylation.Threonine595 phosphorylation of Drp1 by LRRK2 G2019S is required for Drp1-mediated mitochondrial fragmentation and excessive autophagy

SIGNOR-276495

P45985

Q13233

0

phosphorylation

up-regulates activity

0.729

The gck-ctd-mekk1 interaction is sufficiently stable to support mekk1 s phosphorylation of its substrate, sek1

SIGNOR-236380

Q9NW38

Q9BXW9

1

ubiquitination

up-regulates activity

0.9

Thus, eight of the nine components of the FA core complex are FA proteins (FANC‐A, B, C, E, F, G, L, and M). Furthermore, two of the newly discovered FA proteins have enzymatic activities: FANCL is a ubiquitin ligase essential for FANCD2 monoubiquitination in vivo

SIGNOR-263250

A8MYZ6

Q14938

0

transcriptional regulation

down-regulates quantity

0.2

By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development

SIGNOR-268887

P24941

P28482

0

phosphorylation

up-regulates

0.497

In addition to its role in stimulating cyclin d1 expression and nuclear translocation of cdk2, erk regulates thr-160 phosphorylation of cdk2-cyclin e.

SIGNOR-94003

P10914

Q03001

1

transcriptional regulation

down-regulates quantity by repression

0.2

Transient transfection studies with BPAG1 promoter-luciferase reporter gene plasmids and IRF1 and IRF2 expression plasmids revealed that IRF1 and IRF2 directly down-regulated BPAG1 gene transcription in cultured normal human epidermal keratinocytes.

SIGNOR-254492

P63096

P08173

2

binding

up-regulates activity

0.454

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-256686

P42684

Q14689

2

binding

up-regulates activity

0.2

Here, using cultured hippocampal neurons pooled from both sexes of mice, we provide evidence that binding to cortactin tethers Abl2 in spines, where Abl2 and cortactin maintain the small pool of stable actin required for dendritic spine stability.

SIGNOR-266593

P25963

Q9HC78

0

transcriptional regulation

down-regulates quantity by repression

0.259

ChIP and next generation high-throughput DNA sequencing assay showed that ZBTB20 specifically bound to IκBα gene promoter (+1 to +60 region) after TLR activation. ZBTB20 could inhibit IκBα gene transcription, govern IκBα protein expression, and then promote NF-κB activation. Therefore, transcriptional repressor ZBTB20 is needed to promote full activation of TLR signaling and TLR-triggered innate immune response by selectively suppressing the suppressor IκBα gene transcription.

SIGNOR-266868

Q03431

P01270

2

binding

up-regulates

0.772

Here we show that binding of pth to its receptor pth1r induced association of lrp6, a coreceptor of wnt, with pth1r. The formation of the ternary complex containing pth, pth1r, and lrp6 promoted rapid phosphorylation of lrp6, which resulted in the recruitment of axin to lrp6, and stabilization of beta-catenin.

SIGNOR-182039

P14618

Q9P1W9

0

phosphorylation

up-regulates quantity by stabilization

0.37

Here, we identified the protein-serine/threonine kinase PIM2, a known oncogene, as a novel binding partner of PKM2. The interaction between PIM2 and PKM2 was confirmed by multiple biochemical approaches in vitro and in cultured cells. Importantly, we found that PIM2 could directly phosphorylate PKM2 on the Thr-454 residue, resulting in an increase of PKM2 protein levels. Compared with wild type, PKM2 with the phosphorylation-defective mutation displayed a reduced effect on glycolysis

SIGNOR-267472

P00519

Q06830

1

phosphorylation

down-regulates activity

0.387

Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. To determine whether Prxs are phosphorylated, we subjected recombinant human PrxI and II to an in vitro kinase assay with two nonreceptor PTKs, Lck and Abl, in the presence of [γ-32P]ATP. Both PTKs phosphorylated PrxI and PrxII. Phosphorylation of the wild-type protein was detected, whereas that of the Y194F mutant was not (Figure 1B), indicating that Tyr194 is the only site of tyrosine phosphorylation.

SIGNOR-276278

P09467

Q16665

2

binding

down-regulates activity

0.326

FBP1, but not FBP2, suppresses HIF-1a activity by directly binding to its inhibitory domain.

SIGNOR-267590

O96017

P10721

1

phosphorylation

up-regulates

0.286

In this report, we characterize the binding of sh2(chk) to specific phosphotyrosine sites on the c-kit protein sequence. the sh2(chk) binding to the two sites is direct and not through phosphorylated intermediates such as fyn or shc. this indicates that chk binds to the same site on c-kit to which fyn binds, possibly bringing the two into proximity on associated c-kit subunits and leading to the down-regulation of fyn by chk.

SIGNOR-197281

O96001

Q13976

0

phosphorylation

up-regulates

0.656

Recombinant human G-substrate was phosphorylated efficiently by cGMP-dependent protein kinase exclusively at Thr residues, and it was recognized by antibodies specific for rabbit phospho-G-substrate. The amino acid sequences surrounding the sites of phosphorylation in G-substrate are related to those around Thr-34 and Thr-35 of the dopamine- and cAMP-regulated phosphoprotein DARPP-32 and inhibitor-1, respectively, two potent inhibitors of protein phosphatase 1.

SIGNOR-263148

Q9NQS5

P19086

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-257099

Q8N9L9

P0DMV8

2

binding

down-regulates quantity by destabilization

0.2

HSPA1A binds unphosphorylated ACOT4 and promotes its degradation

SIGNOR-271819

P06239

P27986

1

phosphorylation

down-regulates activity

0.623

the regulatory p85 subunit of phosphatidylinositol 3-kinase is phosphorylated on tyrosine residues. We report that this phosphorylation event is readily catalyzed by the Abl and Lck protein-tyrosine kinases in vitro, by Bcr-Abl or a catalytically activated Lck-Y505F in co-transfected COS cells. we have mapped a major phosphorylation site to Tyr-688 in the C-terminal SH2 domain of p85. Tyrosine phosphorylation of p85 in vitro or in vivo was not associated with detectable change in the enzymatic activity of the phosphatidylinositol 3-kinase heterodimer, but correlated with a strong reduction in the binding of some, but not all, phosphoproteins to the SH2 domains of p85.

SIGNOR-251383

P30291

Q8IY84

0

phosphorylation

down-regulates activity

0.48

Furthermore, purified bacterially produced Nim1 kinase directly phosphorylates and inactivates Wee1 in vitro.|Phosphorylation and inactivation of the mitotic inhibitor Wee1 by the nim1 and cdr1 kinase.

SIGNOR-279238

Q13547

O15379

2

binding

up-regulates

0.533

Furthermore, smad7 caused hdac-1 bind to e2f-1 to form a ternary complex on chromosomal dna containing an e2f-binding motif and leading to repression in the activity of the e2f target genes.

SIGNOR-199964

Q13451

Q9NZQ7

1

catalytic activity

up-regulates quantity by expression

0.2

FKBP51s upregulated PD-L1 expression on the plasma membrane by catalysing the protein folding required for subsequent glycosylation. Inhibition of FKBP51s isomerase activity by SAFit decreased PD-L1 levels

SIGNOR-274973

P41597

O60674

0

phosphorylation

up-regulates activity

0.605

JAK2 phosphorylates CCR2 at the Tyr139 position and promotes JAK2/STAT3 complex association to the receptor.

SIGNOR-251345

P20645

O60664

0

relocalization

up-regulates activity

0.73

TIP47 is present in cytosol and on endosomes and is required for MPR transport from endosomes to the trans-Golgi network in vitro and in vivo. TIP47 recognizes a phenylalanine/tryptophan signal in the tail of the cation-dependent MPR that is essential for its proper sorting within the endosomal pathway. These data suggest that TIP47 binds MPR cytoplasmic domains and facilitates their collection into transport vesicles destined for the Golgi.

SIGNOR-253093

O43865

Q9Y6R1

2

binding

up-regulates activity

0.671

IRBIT opposed the effects of WNKs and SPAK by recruiting PP1 to the complex to dephosphorylate CFTR and NBCe1-B, restoring their cell surface expression, in addition to stimulating their activities.

SIGNOR-263135

Q16695

Q15652

0

demethylation

down-regulates activity

0.2

We now determine that JMJD1C is recruited by USF-1 to various lipogenic genes for H3K9 demethylation to enhance chromatin accessibility in the fed state.

SIGNOR-265170

P10415

O75030

0

transcriptional regulation

up-regulates quantity by expression

0.475

MITF directly occupies the BCL2 promoter in vivo and this suggest that BCL2 may be a direct transcriptional target of MITF

SIGNOR-249618

Q99684

P17947

2

binding

down-regulates activity

0.594

Our data demonstrate that GFI-1 physically interacts with PU.1, repressing PU.1-dependent transcription. This repression is functionally significant, as GFI-1 blocked PU.1-induced macrophage differentiation of a multipotential hematopoietic progenitor cell line.

SIGNOR-256043

P35269

2

phosphorylation

down-regulates

0.2

We show that tfiifalpha possesses a serine/threonine kinase activity, allowing an autophosphorylation of the two residues at position serine 385 and threonine 389. Mutation analysis strongly suggests that autophosphorylation of both sites regulates the transcription elongation process.

SIGNOR-69767

Q13526

Q14653

2

binding

down-regulates quantity by destabilization

0.643

Here we report that activation of IRF3 is negatively regulated by the peptidyl-prolyl isomerase Pin1. After stimulation by double-stranded RNA, induced phosphorylation of the Ser339–Pro340 motif of IRF3 led to its interaction with Pin1 and finally polyubiquitination and then proteasome-dependent degradation of IRF3. Suppression of Pin1 by RNA interference or genetic deletion resulted in enhanced IRF-3-dependent production of interferon-beta, with consequent reduction of virus replication.

SIGNOR-252256

P53350

O14757

0

phosphorylation

down-regulates activity

0.314

Chk1 directly phosphorylates Plk1 to disturb its interaction with Sgo1.

SIGNOR-277914

P63096

P35346

2

binding

up-regulates activity

0.496

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-256690

P49841

Q9Y2X9

1

phosphorylation

down-regulates quantity by destabilization

0.2

GSK-3beta phosphorylation-dependent degradation of ZNF281 by beta-TrCP2 suppresses colorectal cancer progression|

SIGNOR-264890

P49674

P35222

1

phosphorylation

down-regulates activity

0.657

Using mass spectrometry and phosphopeptide-specific antibodies, we show that a complex of axin and casein kinase I (CKI) induces Beta-catenin phosphorylation at a single site: serine 45 (S45).

SIGNOR-244102

O14920

Q99759

0

phosphorylation

up-regulates activity

0.569

Genetic analysis showed that MEKK3, which is thought to activate IKK2 through phosphorylation (Yang et al., 2001), is necessary for TNF-alpha-induced NF-kappaB activation.|Our results also suggest that IKK2 is phosphorylated on S177 and S181 on its activation loop by MEKK3.

SIGNOR-279468

O75582

P0C0S8

1

phosphorylation

up-regulates

0.2

We found that msk1 phosphorylated histone h2a on serine 1, and mutation of serine 1 to alanine blocked the inhibition of transcription by msk1.

SIGNOR-123383

O43524

Q13131

0

phosphorylation

up-regulates activity

0.517

Phosphorylation by AMPK leads to the activtion of FOXO3 transcriptional activity without affecting FOXO3 subcellular localization.

SIGNOR-249684

P62140

O15169

1

dephosphorylation

down-regulates activity

0.2

The data suggest that PP1 controls Wnt signaling through interaction with, and regulated dephosphorylation of, axin| Axin phosphorylation markedly enhances the binding of glycogen synthase kinase 3, leading to a more active beta-catenin destruction complex. Wnt-regulated changes in axin phosphorylation, mediated by PP1, may therefore determine beta-catenin transcriptional activity| Four sites, S80, S82, S222, and S473, were identified to be PP1 regulated

SIGNOR-248567

Q92914

P35498

2

binding

down-regulates activity

0.259

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-253422

P17252

P48730

1

phosphorylation

up-regulates activity

0.2

In the present study we analyzed the CK1δ kinase domain for phosphorylation sites targeted by PKCα. Several phosphorylation sites were identified in vitro by initially using GST-CK1δ wild type and phosphorylation-site mutant protein fragments originating from the CK1δ kinase domain. Residues S53, T176, and S181 could finally be confirmed as targets for PKCα. Determination of kinetic parameters of full-length wild type and mutant GST-CK1δ-mediated substrate phosphorylation revealed that integrity of residue T176 is crucial for maintaining CK1δ kinase activity.

SIGNOR-277452

P27361

O60674

1

phosphorylation

down-regulates

0.523

We hypothesize that phosphorylation of ser523 in jak2 by erks 1 and/or 2 or other as-yet-unidentified kinases acts in a negative feedback manner

SIGNOR-146747

Q9UQ80

P07288

1

transcriptional regulation

down-regulates quantity by repression

0.2

Ectopic expression of ebp1, a member of the PA2G4 family, inhibits the proliferation and induces the differentiation of human breast and prostate cancer cell lines. Ebp1 inhibits transcription of E2F1 and androgen receptor regulated genes such as prostate specific antigen (PSA) through its interactions with histone deacetylases (HDACs)

SIGNOR-253662

Q86WA8

Q2T9J0

1

cleavage

down-regulates quantity by destabilization

0.66

Self-cleavage of Tysnd1 in the active oligomer most likely inactivates its protease activity. Subsequently, the cleaved products are degraded by PsLon and removed from the Tysnd1 oligomer.

SIGNOR-261054

Q16625

P05129

0

phosphorylation

up-regulates activity

0.307

Protein kinase C regulates the phosphorylation and cellular localization of occludin. Ser(338) of occludin was identified as an in vitro protein kinase C phosphorylation site using peptide mass fingerprint analysis and electrospray ionization tandem mass spectroscopy. Both the phosphorylation of occludin and its incorporation into tight junctions induced by calcium switch were markedly inhibited by the PKC inhibitor GF-109203X.

SIGNOR-249107

Q99748

P56159

2

binding

up-regulates

0.738

A receptor complex comprised of trnr1 (gdnfr alpha) and ret was recently identified and found to be capable of mediating both gdnf and ntn signaling

SIGNOR-49119

P16284

P41240

0

phosphorylation

up-regulates activity

0.55

We demonstrated that phosphorylation of PECAM-1 by Src or Csk family kinases was sufficient to trigger its association with SHP-2. Moreover, it was able to promote binding of PECAM-1 to SHP-1, a SHP-2-related protein-tyrosine phosphatase expressed in hemopoietic cells. Taken together, these findings indicated that the Src and Csk families of kinases are strong candidates for mediating tyrosine phosphorylation of PECAM-1 and triggering its association with SH2 domain-containing phosphatases under physiological circumstances.

SIGNOR-262741

P27361

Q9BRX9

2

binding

up-regulates

0.508

Morg1 specifically associates with several components of the erk pathway, including mp1, raf-1, mek, and erk, and stabilizes their assembly into an oligomeric complex.

SIGNOR-124473

Q16236

O96013

0

phosphorylation

down-regulates quantity by destabilization

0.2

PAK4 directly phosphorylated Nrf2 at T369, and it led to its nuclear export and proteasomal degradation, all of which impaired antioxidant responses in hepatocytes.

SIGNOR-277583

Q9HCU9

O43791

0

ubiquitination

down-regulates quantity

0.402

Intriguingly, BRMS1 turns out to be a potent substrate that is ubiquitinated by the Cul3-SPOP complex. Knockdown of SPOP increases the level of BRMS1 protein and represses the expression of BRMS1 repressive target genes such as OPN and uPA in breast cancer cells.

SIGNOR-268857

P07900

P29474

2

binding

up-regulates

0.76

The binding of hsp90 to enos enhances the activation of enos.

SIGNOR-57211

O00744

Q9UP38

2

binding

up-regulates

0.664

Inhibition of adipogenesis by wnt10b is likely mediated by wnt receptors, frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor-related proteins 5 and 6

SIGNOR-89134

P01106

Q06203

1

transcriptional regulation

up-regulates quantity by expression

0.2

PPAT, catalyzing the first step of purine synthesis, and DHODH, an enzyme generating uridine in the middle of the pyrimidine synthesis pathway, were validated as direct c-MYC target genes by all criteria.

SIGNOR-267381

O15524

P15498

2

binding

down-regulates quantity by destabilization

0.598

SOCS1 stimulates the polyubiquitination of VAV proteins in vivo, which was stabilized by proteasomal inhibitors. These results suggest that SOCS1 programs VAV degradation by acting as a substrate-specific recognition component of a VCB-like ubiquitin ligase complex.

SIGNOR-272559

P07949

P39905

2

binding

up-regulates

0.91

A receptor complex comprised of trnr1 (gdnfr alpha) and ret was recently identified and found to be capable of mediating both gdnf and ntn signaling

SIGNOR-49094

Q8IXL6

P07237

1

phosphorylation

up-regulates activity

0.387

The secretory pathway kinase Fam20C phosphorylates Ser357 of PDI and responds rapidly to various ER stressors. Phosphorylation of Ser357 induces an open conformation of PDI and turns it from a "foldase" into a "holdase", which is critical for preventing protein misfolding in the ER. Phosphorylated PDI also binds to the lumenal domain of IRE1α, a major UPR signal transducer, and attenuates excessive IRE1α activity.

SIGNOR-275574

P05129

P49840

1

phosphorylation

down-regulates

0.324

Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.

SIGNOR-115726

Q05086

P04637

1

ubiquitination

down-regulates quantity

0.681

E6-AP also directly ubiquitylated p53 in an in vitro ubiquitylation assay.|Our result suggests that E6-AP not only enhances the degradation of p53 but also regulates the neuronal cell growth.

SIGNOR-278681

O95944

P12004

2

binding

down-regulates activity

0.307

NK cells play an important role in the early immune response to cancer. The NKp44 activating receptor is the only natural cytotoxicity receptor that is expressed exclusively by primate NK cells, yet its cellular ligands remain largely unknown.

SIGNOR-260043

P31273

O43541

2

binding

up-regulates activity

0.529

Smad6 interacts with hox transcription factors as part of the negative feedback circuit in the bmp signaling pathway

SIGNOR-75823

Q96GD4

Q9UKC9

2

binding

down-regulates quantity by destabilization

0.483

The SCF complex contains a catalytic core consisting of Skp1, Cullin1, and the E2 ubiquitin-conjugating (Ubc) enzyme and a F box component that acts as a receptor targeting numerous substrates via phosphodegron elicited interactions. our screening studies suggested that FBXL2 also targets Aurora B protein for ubiquitination and degradation.

SIGNOR-272097

Q9NTX7

Q9H2K2

1

ubiquitination

down-regulates quantity

0.614

We show that RNF146, tankyrase, and Axin form a protein complex, and that RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation.

SIGNOR-260005

Q14738

P17612

0

phosphorylation

up-regulates

0.2

Protein kinase a activates protein phosphatase 2a by phosphorylation of the b56delta subunit.

SIGNOR-153218

Q9Y3Z3

P06493

0

phosphorylation

down-regulates

0.492

Cyclin a2/cdk1 phosphorylates samhd1 at the threonine 592 residue both in vitro and in vivo. Phosphorylation of samhd1 thr592 correlates with loss of its ability to restrict hiv-1.

SIGNOR-201913

P68400

P54252

1

phosphorylation

up-regulates activity

0.2

Here we show that protein casein kinase 2 (CK2)-dependent phosphorylation controls the nuclear localization, aggregation and stability of ataxin-3 (ATXN3), the disease protein in spinocerebellar ataxia type 3 (SCA3). The main phosphorylation of ATXN3 in vivo thus occurred at serine residues within the three conserved UIMs.

SIGNOR-276224

P11309

Q16665

1

phosphorylation

up-regulates quantity by stabilization

0.2

PIM1 kinase directly phosphorylates HIF-1α at threonine 455, a previously uncharacterized site within its oxygen-dependent degradation domain. This phosphorylation event disrupts the ability of prolyl hydroxylases to bind and hydroxylate HIF-1α, interrupting its canonical degradation pathway and promoting constitutive transcription of HIF-1 target genes.

SIGNOR-277311

Q9UBK2

P16220

0

transcriptional regulation

up-regulates quantity by expression

0.554

CREB was found to induce expression of the gluconeogenic programme through the nuclear receptor coactivator PGC-1, which is shown here to be a direct target for CREB regulation in vivo

SIGNOR-256150

Q9UKA1

Q14203

2

binding

down-regulates quantity by destabilization

0.462

FBXL5 binds to p150(Glued)in vitro and in vivo. FBXL5 and p150(Glued) co-localize primarily in the cytoplasm with peri-nuclear enrichment in HeLa cells. Overexpression of FBXL5 promotes poly-ubiquitination of p150(Glued) and protein turnover of p150(Glued). Our findings provide a potential mechanism by which p150(Glued) protein function is regulated by SCFs.

SIGNOR-271652

Q92558

P12931

0

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

P68400

P35221

1

phosphorylation

down-regulates

0.39

We demonstrate here that egfr activation results in disruption of the complex of beta-catenin and alpha-catenin, thereby abrogating the inhibitory effect of alpha-catenin on beta-catenin transactivation via ck2alpha-dependent phosphorylation of alpha-catenin at s641.

SIGNOR-161847

Q15139

Q15276

1

phosphorylation

up-regulates activity

0.382

PKD phosphorylates Rabaptin-5 at Ser407, and this controls alphavbeta3 and alpha5beta1 integrin and EGFR recycling.

SIGNOR-278192

O14559

P63000

1

gtpase-activating protein

down-regulates activity

0.444

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-260491

P40238

Q8WWM7

2

binding

down-regulates

0.353

A2d binds to cytokine receptors mpl and epo-r. A2d is associated with these unoccupied receptorsin vivo,and stimulation with tpo or epo causes the rapid dissociation of a2d from the activated receptor.

SIGNOR-113891

Q9HC23

Q8NFJ6

2

binding

up-regulates

0.665

We have cloned two closely related receptors for pk1 and pk2. These receptors, named prokineticin receptor 1 and 2 (pkr1 and pkr2)

SIGNOR-87919

P00533

Q9UBN7

1

phosphorylation

down-regulates

0.44

A negative feedback loop consisting of egfr-mediated phosphorylation of hdac6 tyr(570) resulted in reduced deacetylase activity and increased acetylation of alpha-tubulin.

SIGNOR-162431

P19086

P24530

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-257321

Q05513

Q07812

1

phosphorylation

down-regulates activity

0.2

Protein kinase czeta abrogates the proapoptotic function of bax through phosphorylation. Overexpression of wild type or the constitutively active a119d but not the dominant negative k281w pkczeta mutant results in bax phosphorylation at serine 184.

SIGNOR-155111

P23443

O60331

1

phosphorylation

down-regulates quantity by destabilization

0.2

Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKIγ90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKIγ90 phosphorylation is essential for cell migration and invasion. These data suggest that S6K1-mediated PIPKIγ90 phosphorylation regulates cell migration and invasion by controlling PIPKIγ90 degradation.

SIGNOR-277283

O95837

P21462

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-256961

P09471

Q9H244

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-256991

O43150

Q14289

0

phosphorylation

up-regulates activity

0.525

Tyrosine phosphorylation of Pap by Pyk2 or Src kinases. We have identified a new Pyk2 binding protein designated Pap. Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. We demonstrate that Pap forms a stable complex with Pyk2 and that activation of Pyk2 leads to tyrosine phosphorylation of Pap in living cells.

SIGNOR-269704

Q9UDT6

Q7Z460

2

binding

up-regulates activity

0.594

CLIP-associating protein (CLASP) 1 and CLASP2 are mammalian microtubule (MT) plus-end binding proteins, which associate with CLIP-170 and CLIP-115.|We demonstrate that the middle part of CLASPs binds directly to EB1 and to MTs. | Both EB1- and cortex-binding domains of CLASP are required to promote MT stability.

SIGNOR-265092

P42224

O15111

0

phosphorylation

up-regulates activity

0.331

In addition, IKK\u03b1 also phosphorylated STAT1 in a type I IFN-independent manner [Fig 8, a dashed line (B)].

SIGNOR-279732

P04150

P49715

1

transcriptional regulation

up-regulates quantity by expression

0.455

We show that in addition, DEX-bound GR directly promotes the expression of adipogenic TFs, including C/EBPβ, Klf5, Klf9, and C/EBPα

SIGNOR-256116

P35398

O00327

1

transcriptional regulation

up-regulates quantity by expression

0.689

Direct Regulation of the NPAS2 Promoter by RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding.

SIGNOR-267982

P53004

P06213

0

phosphorylation

up-regulates activity

0.479

Human BVR (hBVR) also reduces the hemeoxygenase activity product biliverdin to bilirubin and is directly activated by insulin receptor kinase (IRK).|in addition to Y198 in the YMKM motif, 2 other tyrosines, Y228 in the YLSF motif and Y291 in the C-terminus of the protein, are directly phosphorylated by IRK

SIGNOR-275514

P23528

Q76I76

0

dephosphorylation

up-regulates activity

0.732

Differential activities, subcellular distribution and tissue expression patterns of three members of Slingshot family phosphatases that dephosphorylate cofilin.|Cofilin, a key regulator of actin filament dynamics, is inactivated by phosphorylation at Ser-3 by LIM-kinases and is reactivated by dephosphorylation by a family of protein phosphatases, termed Slingshot (SSH).

SIGNOR-248733

P51828

Q05655

0

phosphorylation

up-regulates activity

0.555

Immunoprecipitation data indicated that PKCdelta could bind and directly phosphorylate AC7.

SIGNOR-279258

Q9UQM7

Q86UR5

1

phosphorylation

up-regulates

0.347

Two serine residues in rim1 (ser-241 and ser-287) and one serine residue in rim2 (ser-335) were required for 14-3-3 binding. Incubation with ca2+/calmodulin-dependent protein kinase ii greatly stimulated the interaction of recombinant n-terminal rim but not the s241/287a mutant with 14-3-3,

SIGNOR-103890

Q12983

Q15382

2

binding

down-regulates

0.751

Bnip3, a hypoxia-inducible bcl-2 homology 3 domain-containing protein, directly binds rheb and inhibits the mtor pathway. Bnip3 decreases rheb gtp levels in a manner depending on the binding to rheb.

SIGNOR-158274

Q5VWQ8

P10275

2

binding

down-regulates activity

0.328

DAB2IP acts as a scaffold protein for PP2A to suppress DHT-elicited S81 phosphorylation of the AR, preventing its nuclear translocation and binding to androgen response elements. In addition, DAB2IP can compete with the AR for binding to c-Src, thus blocking the non-genomic AR pathway

SIGNOR-254758

P01189-PRO_0000024969

Q01726

2

binding

up-regulates activity

0.2

The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins

SIGNOR-268701

Q92630

P04637

1

phosphorylation

up-regulates

0.67

Here, we demonstrate that the dual-specificity tyrosine-phosphorylation-regulated kinase 2 (dyrk2) directly phosphorylates p53 at ser46. these findings indicate that dyrk2 regulates p53 to induce apoptosis in response to dna damage.

SIGNOR-153544

P28482

Q9BYB0

1

phosphorylation

down-regulates activity

0.2

Interestingly, we discovered that several kinases in the MEK and ERK2 pathway destabilize Shank3 and that genetic deletion and pharmacological inhibition of ERK2 increases Shank3 abundance in vivo.|We also determined that phosphorylation of Shank3 by ERK2 at selective residues promotes its ubiquitination and degradation.

SIGNOR-279538

P08651

O00712

2

binding

down-regulates activity

0.362

Coexpression of NFI-B3 with other isoforms of the NFI-B, -C, and -X family, however, led to a strong reduction of transcriptional activation compared with the expression of these factors alone. NFI-B3 apparently forms heterodimers with other NFI proteins thereby interfering with their function.

SIGNOR-240880