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
P19784	Q9Y5B0	1	phosphorylation	down-regulates activity	0.374	We found that only phosphorylated FCP1 can physically interact with TFIIF. We set out to purify an FCP1 kinase from HeLa cells and identified casein kinase 2, which, surprisingly, displayed a negative effect on FCP1-associated activities.\| Phosphorylation of FCP1 by CK2 Inhibits the Transcription Elongation Activity of FCP1. \| Two in vivo phosphorylation sites within the C terminus of FCP1 at Ser-575 and Ser-740 were identified	SIGNOR-250986
Q9Y6Q9	P18848	2	binding	up-regulates activity	0.2	Mechanistically, Dyrk3 directly phosphorylated NCOA3 at Ser-1330, disrupting its binding to ATF4 and thereby causing the inhibition of ATF4 transcriptional activity.	SIGNOR-275452
P67775	P31314	2	binding	down-regulates activity	0.308	HOX11 also inhibited PP2A serine/threonine phosphatase activity concomitant with stimulation of the AKT/PKB signaling cascade.	SIGNOR-240719
P03372	O00459	2	binding	up-regulates	0.545	Recently, it has been known that er activates phosphatidylinositol-3-oh kinase (pi3k) through binding with the p85 regulatory subunit of pi3k.	SIGNOR-140473
P19838	O14757	0	phosphorylation	down-regulates	0.275	Taken together, the above findings suggest that chk1 phosphorylates p50 at s329 and further, that this phosphorylation blocks p50 dna binding.	SIGNOR-195208
P07949	P31749	1	phosphorylation	up-regulates	0.323	The PKB Y315 residue, which is known to be phosphorylated by Src tyrosine kinase, was also a major site of phosphorylation by RET/PTC. RET/PTC-mediated tyrosine phosphorylation results in the activation of PKB kinase activity	SIGNOR-252619
P50750	Q9H0D6	1	phosphorylation	up-regulates activity	0.278	Among the RNA processing factors phosphorylated by Cdk9 was the 5'-to-3' "torpedo" exoribonuclease Xrn2, required in transcription termination by Pol II, which we validated as a bona fide P-TEFb substrate in vivo and in vitro. Phosphorylation by Cdk9 or phosphomimetic substitution of its target residue, Thr439, enhanced enzymatic activity of Xrn2 on synthetic substrates in vitro.	SIGNOR-277194
Q9Y243	Q92934	1	phosphorylation	down-regulates	0.542	Ser-136 is the major phosphoacceptor site for akt;akt can weakly phosphorilate ser-155.	SIGNOR-81122
Q9UNE7	Q13485	1	polyubiquitination	down-regulates quantity by destabilization	0.396	We demonstrate that the coexpression of Smad1 and Smad4 with the CHIP protein results in the degradation of the Smad proteins through a ubiquitin-mediated process.	SIGNOR-272947
O75882	P42127	2	binding	up-regulates	0.391	Attractin is a low-affinity receptor for agouti protein, but not agrp, in vitro and in vivo.	SIGNOR-85496
P68400	P13569	1	phosphorylation	down-regulates	0.278	Cftr possesses two ck2 phosphorylation sites (s422 and t1471) the t1471 residue, previously described as a site for cftr phosphorylation by ck2 (25), seems to be critical for cftr turnover and processing.	SIGNOR-176627
P29275	P08754	2	binding	up-regulates activity	0.279	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-257152
P19484	P10619	1	transcriptional regulation	up-regulates quantity by expression	0.298	Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy\|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1\|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants	SIGNOR-276549
P36888	P06241	0	phosphorylation	up-regulates activity	0.292	FYN phosphorylates FLT3 on tyrosine residues (A\u2013B) COS1 cells were transfected with plasmids expressing FLT3 wild-type and FYN wild-type or mutants.\|It was not completely unexpected that FYN associates wild-type FLT3 in the absence of ligand stimulation in COS-1 cells, as overexpression of wild-type FLT3 results in ligand independent activation of FLT3 (data not shown).	SIGNOR-279715
Q96P68	P09471	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-257243
P17612	P61224	1	phosphorylation	up-regulates	0.522	These results provide a mechanistic explanation for the differential effects of rap1 phosphorylation by pka on effector protein interaction. camp is one among several pathways leading to rap1 activation	SIGNOR-187410
P01375	P48736	2	binding	up-regulates	0.296	Tnf activates phosphatidylinositol-3-oh kinase (pi(3)k)	SIGNOR-70625
P09471	P08912	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-257009
Q9UKT4	Q9UJX3	2	binding	down-regulates	0.458	Emi1 can inhibit apc already activated by cdc20 or cdh1.	SIGNOR-113382
P01189	Q01726	2	binding	up-regulates activity	0.766	Alpha-melanocyte stimulating hormone (alpha-MSH) binds to melanocortin-1 receptor (MC1R) on melanocytes to stimulate pigmentation and modulate various cutaneous inflammatory responses.	SIGNOR-252370
Q8IZU9	O14936	2	binding	up-regulates activity	0.459	A Missense De Novo Variant in the CASK-interactor KIRREL3 Gene Leading to Neurodevelopmental Disorder with Mild Cerebellar Hypoplasia. KIRREL3 is a gene important for the central nervous system development-in particular for the process of neuronal migration, axonal fasciculation, and synaptogenesis-and colocalizes and cooperates in neurons with CASK gene.	SIGNOR-269078
Q9H1J7	O75581	2	binding	up-regulates	0.625	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-131888
Q9P2K8	P05198	1	phosphorylation	down-regulates activity	0.914	Translation initiation factor 2α [eukaryotic translation initiation factor 2α (eIF2α)] kinase phosphorylates serine51 (Ser51) of eIF2α and downregulates cellular protein synthesis.	SIGNOR-246157
P05106	Q9Y490	2	binding	up-regulates activity	0.793	Over the past 10 years, the binding of talin to the cytoplasmic tail of integrin-β subunits has been established to have a key role in integrin activation. Binding of the phosphotyrosinebinding (PTB)-domain-like subdomain of the protein 4.1, ezrin, radixin, moesin (FERM) domain of talin to the conserved WxxxNP(I/L)Y motif of the β-integrin tail permits additional weaker interactions between talin and the membrane-proximal region of the tail that trigger integrin activation, probably through the disruption of inhibitory interactions between α- and β-subunit cytoplasmic tails.	SIGNOR-257625
P06730	O00571	2	binding	down-regulates activity	0.628	DDX3 is a human RNA helicase with plethoric functions. we identified translation initiation factor eukaryotic initiation factor 4E (eIF4E) as a DDX3-binding partner. Interestingly, DDX3 utilizes a consensus eIF4E-binding sequence YIPPHLR to interact with the functionally important dorsal surface of eIF4E in a similar manner to other eIF4E-binding proteins. Furthermore, cap affinity chromatography analysis suggests that DDX3 traps eIF4E in a translationally inactive complex by blocking interaction with eIF4G.	SIGNOR-269193
P49768	Q92542	2	binding	up-regulates	0.965	Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2.	SIGNOR-118852
P51843	Q9Y618	2	binding	up-regulates activity	0.393	The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes.	SIGNOR-271785
P29320	Q13153	1	phosphorylation	up-regulates activity	0.277	Etk kinase directly phosphorylates and activates PAK1 in response to estrogen.\|We demonstrated that estrogen-activated Etk directly phosphorylated PAK1 on Tyr153.	SIGNOR-278398
P43487	P53350	0	phosphorylation	up-regulates activity	0.359	Here, we demonstrated in vitro and in vivo phosphorylation of RanBP1 by Plk1 as well as the importance of phosphorylation of RanBP1 in the interaction between Plk1 and Ran during early mitosis.	SIGNOR-279751
Q01718	P63092	2	binding	up-regulates activity	0.516	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-268694
O14763	P25490	0	transcriptional regulation	down-regulates quantity by repression	0.403	Depletion of FKBP51 impairs the acetylation status of YY1 and interferes with its binding on the DR5 promoter. The lack of the repressor activity of YY1 increases DR5 transcription and sensitizes melanoma cell to TRAIL-induced apoptosis.	SIGNOR-268793
P15248	Q01113	2	binding	up-regulates	0.751	Interleukin 9 (il-9) exerts its pleiotropic effects through the il-9 receptor (il-9r) complex, which consists of the il-9r alpha-chain, which determines the cytokine specificity, and the il-2 receptor gamma-chain	SIGNOR-73601
O75874	P36888	0	phosphorylation	up-regulates activity	0.424	Moreover, in an in vitro kinase assay, purified recombinant FLT3 (rFLT3) phosphorylated recombinant IDH2 R140Q mutant but did not alter its catalytic activity (Figure 1C), whereas rFLT3 phosphorylated mIDH1 protein and enhanced its catalytic activity	SIGNOR-267630
Q12933	P20333	2	binding	up-regulates activity	0.708	Our analysis indicates that traf1 and traf2 are associated with the cytoplasmic domain of tnf-r2 in a heterodimeric complex in which traf2 contacts the receptor directly.	SIGNOR-34645
O95405	Q15796	1	relocalization	up-regulates activity	0.908	Smad anchor for receptor activation (SARA) is known as Smad cofactor that interacts directly with Smad2/3 and functions to recruit Smad2/3 to the TGF-beta receptor.	SIGNOR-165786
Q00987	P06400	1	ubiquitination	down-regulates quantity by destabilization	0.667	In this study, we found that Mdm2, a ubiquitin ligase for p53, promoted ubiquitin-dependent degradation of pRB	SIGNOR-278530
P15924	Q99959	2	binding	up-regulates quantity by stabilization	0.787	In contrast to the proper membrane localization of PKP2 and DSP after cotransfection of both WT proteins, mutant PKP2 C796R protein was not able to interact with FLAG-DSP to enable assembly at the junctional plaque, indicating the requirement of functional PKP2 for DSP integration into the desmosome.	SIGNOR-261254
P84022	Q16539	0	phosphorylation	up-regulates activity	0.537	Smad3 was phosphorylated at both Ser203 and Ser207 in untreated MCF10CA1h cells and the p38 and ROCK inhibitors each down-regulated phosphorylation at these sites. we demonstrate that phosphorylation at Ser203 and Ser207 residues is required for the full transactivation potential of Smad3, and that these residues are targets of the p38 and Rho/ROCK pathways.	SIGNOR-250112
P06748	Q9P275	0	deubiquitination	up-regulates quantity by stabilization	0.39	USP36 deubiquitylated the nucleolar proteins nucleophosmin/B23 and fibrillarin, and stabilized them by counteracting ubiquitylation-mediated proteasomal degradation.	SIGNOR-272290
Q00535	O15516	1	phosphorylation	up-regulates	0.328	Cdk5 phosphorylates clock at the thr-451 and thr-461 residues in association with transcriptional activation of clock.	SIGNOR-203227
P45973	P68431	2	binding	up-regulates activity	0.2	A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing.	SIGNOR-264490
O14757	O60566	1	phosphorylation	up-regulates activity	0.447	Nonetheless, in our experimental system a Chk1-dependent BubR1 phosphorylation was also observed after Noc treatment.\|Possible requirement of Chk1 in U2OS cells to activate the mitotic spindle checkpoint proteins Mad2 and BubR1.	SIGNOR-280223
P55064	P17612	0	phosphorylation	up-regulates activity	0.2	AQP5 can be directly phosphorylated by PKA at Ser 156 \|Our data hint at a mechanism whereby phosphorylation of Ser 156 in AQP5 increases its membrane localization, thereby enhancing cancer cell proliferation.	SIGNOR-272088
Q9H2X6	P15923	1	phosphorylation	down-regulates activity	0.2	This result provides a mechanistic explanation for the context-dependent function of HIPK2 in Wnt signaling	SIGNOR-279193
Q16566	P49841	1	phosphorylation	down-regulates activity	0.263	CAMK4 phosphorylates GSK3\u03b2 at serine 9, which leads to its inactivation. xref Accordingly, we examined the levels of phosphorylated GSK3\u03b2 at serine 9 (pGSK3\u03b2-ser9) in podocytes exposed to IgG from TG patients and calculated the ratio of pGSK3\u03b2-ser9 to total GSK3\u03b2.	SIGNOR-279142
Q13627	P08151	1	phosphorylation	up-regulates activity	0.514	Here, we have used an in vitro kinase assay and phospho-peptide mass spectrometry analysis to identify site(s) of direct phosphorylation of GLI1 by DYRK1A and have determined that DYRK1A phosphorylates GLI1 at Ser408 within its nuclear localization sequence.\|The kinase DYRK1A (dual-specificity tyrosine phosphorylation regulated kinase 1a) has been shown to activate GLI1 via a phosphorylation event, leading to the translocation of GLI1 from the cytoplasm to the nucleus .	SIGNOR-278930
Q96S66	A0A0B4J2F0	2	binding	up-regulates activity	0.2	The PIGBOS microprotein interacts with the ER protein CLCC1. PIGBOS localizes to the mitochondrial outer membrane where itinteracts with the ER protein CLCC1 at ER–mitochondria contact sites. PIGBOS-CLCC1 interaction is necessary for PIGBOS function	SIGNOR-261040
P17252	P08567	1	phosphorylation	up-regulates	0.28	To determine the role of pkc-dependent phosphorylation in pleckstrin function, we mapped the phosphorylation sites in vivo of wild-type and site-directed mutants of pleckstrin expressed in cos cells. Phosphorylation was found to occur almost exclusively on ser-113 and ser-117. Replacing all these sites with glycine decreased phosphorylation by > 90% and reduced pleckstrin's ability to inhibit phosphoinositide hydrolysis by as much as 80%.	SIGNOR-40048
P56705	O75197	2	binding	up-regulates	0.649	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-131832
P27361	P43364	1	phosphorylation	up-regulates	0.3	Mage-11 ser-174 appears to be a post-translational regulatory site phosphorylated by erk1, based on the inhibitory effect of the s174a mutation in the context of shorter ar nh2-terminal fragments (19), and the greater transcriptional activity of gal-mage-11 fusion proteins containing the s174d phosphomimetic.	SIGNOR-188466
P61011	Q01130	2	binding	up-regulates activity	0.341	We have now demonstrated that p54 interacts not only with SC35 and ASF/SF2 but also with U2AF. Pairwise interactions between p54 and other RS domain-containing spliceosomal proteins in comparison with SC35 and ASF/SF2 as detected by the yeast two-hybrid interaction assay. . It is conceivable that p54 can mediate 59 and 39 splice site interaction by interacting directly with U2AF65 associated with the 39 splice site and at the same time interact with other SR proteins, such as ASF/SF2 and SC35, which in turn interact with U1-70K. In this scenario, p54 is different from SC35 or ASF/SF2 in that it cannot directly interact with the 59 component (U1-70K) but can interact with the protein associated with the 39 splice site (U2AF65).	SIGNOR-261160
Q9Y6W8	O75144	2	binding	up-regulates activity	0.2	ICOSL expression is largely restricted to professional antigen-presenting cells (APCs), including B cells [in which ICOSL is regulated by BAFFR and non-canonical NFκB signaling (20)], macrophages, and dendritic cells (DCs) (12, 17, 21, 22), but is also expressed by certain endothelial cells (23) and lung epithelium	SIGNOR-272497
P04083	P25089	2	binding	up-regulates activity	0.618	We show that the mimetic N-terminal annexin 1 peptide Ac1-25 is able to activate and desensitize not only FPR but also FPRL1 and FPRL2.	SIGNOR-259438
P14316	Q8IU81	2	binding	up-regulates activity	0.692	We have identified two novel proteins that interact specifically with the C-terminal repression domain of Interferon Regulatory Factor-2 (IRF-2). These proteins, which we term IRF-2 binding proteins 1 and 2 (IRF-2BP1 and IRF-2BP2, the latter having two splicing isoforms, A and B), are nuclear proteins, and have the properties of IRF-2-dependent transcriptional co-repressors that can inhibit both enhancer-activated and basal transcription in a manner that is not dependent upon histone deacetylation.	SIGNOR-224045
P29353	Q05655	0	phosphorylation	up-regulates	0.569	Pkc delta phosphorylates p52shca at ser29 to regulate erk activation in response to h2o2.	SIGNOR-149398
P41145	P63096	2	binding	up-regulates activity	0.475	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-256710
P49841	Q12888	1	phosphorylation	up-regulates activity	0.283	Based on these observations, we hypothesized that the IR induced GSK3beta nuclear translocation may activate 53BP1 via phosphorylation at the S/T-Q motif.\|Importantly, our in vivo and in vitro data clearly indicated that GSK3\u03b2 induced the phosphorylation of 53BP1 at the Ser166 site.	SIGNOR-278226
P08236	Q9NR19	0	transcriptional regulation	up-regulates quantity by expression	0.262	Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy\|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1\|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants	SIGNOR-276554
Q15642	Q99996	2	binding	up-regulates activity	0.512	Mechanistically, AKAP-9 interacted with cdc42 interacting protein 4 (CIP4) and regulated its expression. CIP4 levels were interrelated to the AKAP-9 level in CRC cells. Functionally, AKAP-9 was essential for TGF-β1-induced epithelial-mesenchymal transition of CRC cells, and CIP4 played a critical role in mediating the function of AKAP-9. Importantly, CIP4 expression was significantly up-regulated in human CRC tissues.\|Co-immunoprecipitation assay revealed that AKAP-9 and CIP4 physically interacted with each other in Lovo and HT29 cells (Fig. 4B and C).	SIGNOR-260303
P02775	P35372	1	chemical inhibition	down-regulates activity	0.385	Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors.	SIGNOR-258413
P99999	O14727	2	binding	up-regulates activity	0.792	During apoptosis, Apaf-1 binds to cytochrome c and in the presence of ATP/dATP forms an apoptosome, leading to the recruitment and activation of the initiator caspase, caspase-9.	SIGNOR-135384
Q9Y2G2	P55211	2	binding	down-regulates	0.425	Tucan is a recently identified card-containing protein that can complex with caspase-9 and prevent cytochrome c-induced caspase activation.	SIGNOR-146663
P27361	P53805	1	phosphorylation	up-regulates activity	0.38	Consensus phosphorylation sites for p42/44 MAPK and GSK-3 are present in the SP repeat of MCIP1 at serine 112 and serine 108, respectively \|Several endogenous proteins are capable of inhibiting the catalytic activity of calcineurin. Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these proteins on the basis of its pattern of expression and its function in a negative feedback loop to regulate calcineurin activity. Here we show that MCIP1 can be phosphorylated by MAPK and glycogen synthase kinase-3 and that phosphorylated MCIP1 is a substrate for calcineurin.	SIGNOR-249478
Q13523	Q9Y2Y9	1	phosphorylation	down-regulates	0.342	Using yeast two-hybrid screening of a human thymus cdna library, prp4, a serine/threonine protein kinase, was identified as a klf13-binding protein...coexpression of prp4 and klf13 increases nuclear localization of klf13 and ccl5 transcription.	SIGNOR-154951
P63096	P46663	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-257036
Q16581	P35626	0	phosphorylation	down-regulates activity	0.2	These findings suggest that in agonist-stimulated mast cells GRK2 and GRK3 may phosphorylate C3aR at the same or distinct sites to promote receptor desensitization.	SIGNOR-279781
P51965	P29372	2	binding	up-regulates activity	0.2	Here we report that MID1 catalyzes the in vitro ubiquitination of the catalytic subunit of PP2A (PP2Ac) in the absence of alpha4. In the presence of alpha4, the level of PP2Ac ubiquitination is reduced.The high molecular weight smear pattern was not as obvious, suggesting that domains within the C-terminal half of MID1 may contribute to the polyubiquitination of PP2Ac. We observed that PP2Ac was ubiquitinated in the presence of UbcH5a-c and UbcH6, similar to results obtained with MID1-catalyzed ubiquitination of alpha4 (Figure 2E)	SIGNOR-271929
Q13105	P51610	2	binding	down-regulates activity	0.344	We show here that HCF-1 directly binds to the Myc-interacting protein Miz-1. HCF-1 Represses Gal4-Miz-1-mediated Transcriptional Activation	SIGNOR-223590
P02671	P20702	2	binding	up-regulates	0.387	To map the binding sites for four distinct ligands for mac-l: ic3b, fibrinogen, icam-1. __the i domain on the ot chain of mac-1 is an important recognition site for all four ligands.	SIGNOR-31320
Q12774	P12931	0	phosphorylation	up-regulates activity	0.465	Arhgef5 was tyrosine-phosphorylated by Src and bound to Src to positively regulate its activity.\|Using an inducible system for Src activation, we found that Src induced podosome formation depends upon the Src SH3 domain, and identified Arhgef5 as a Src SH3 binding protein.	SIGNOR-279571
Q8WYQ5	P00519	0	phosphorylation	up-regulates activity	0.2	The kinase ABL phosphorylates the microprocessor subunit DGCR8 to stimulate primary microRNA processing in response to DNA damage. When coexpressed in HEK293T cells, ABL phosphorylated DGCR8 at Tyr(267).	SIGNOR-262604
Q15172	P17252	0	phosphorylation	down-regulates activity	0.341	In this study, we identified a novel phosphorylation site at Ser(41) of B56α. This phosphoamino acid residue was efficiently phosphorylated in vitro by PKCα.	SIGNOR-276603
Q15109	P06702	2	binding	up-regulates activity	0.346	RAGE and TLR4 are well-characterized S100A8 and S100A9 receptors and expressed in AML cells Once secreted, S100A8 and S100A9 induce immune and inflammatory responses9 through interaction with receptors such as Toll-like receptor 4 (TLR4), receptor for advanced glycation end-product (RAGE), and CD33	SIGNOR-261920
O95551	P36896	0	phosphorylation	up-regulates activity	0.28	ALK4 phosphorylated TTRAP in vitro (Fig. 6A). The band migrating at the position of TTRAP was excised and analyzed by LC-MS/MS. One TTRAP peptide was phosphorylated either on T88 and T92, or on T92 only (Fig. 6B).We tested in vivo phosphorylation of Strep-TTRAP by co-expression with mouse Alk4 in HEK293T cells, and affinity-purified TTRAP. In this preparation TTRAP-specific peptides were reproducibly found in both the singly (T92) and doubly phosphorylated form (T88/T92). mutant TTRAPT88A,T92A is not able to rescue the TtrapMO phenotype, suggesting that phosphorylation of Ttrap on Thr88 and Thr92 is essential for Ttrap function.	SIGNOR-262612
Q15118	Q16513	1	phosphorylation	up-regulates activity	0.338	PDK1 phosphorylates the PRKs at their conserved activation loop threonines (Thr-774 and Thr-816 for PRK1 and PRK2, respectively) both in vitro and in vivo.	SIGNOR-250265
Q96PU5	Q9NRA0	1	ubiquitination	down-regulates quantity by destabilization	0.2	In this study, we found that NEDD4L interacted with SphK2 to ubiquitinate SphK2 protein.\|NEDD4L Mediates the Degradation of SphK2 Protein Through the Ubiquitin-Proteasomal Pathway.	SIGNOR-278660
Q9H228	P08754	2	binding	up-regulates activity	0.385	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256819
O95136	Q03113	2	binding	up-regulates	0.47	Serum-borne lysophosphatidic acid (lpa) and sphingosine 1-phosphophate (s1p) act through g12/13-coupled receptors to inhibit the hippo pathway kinases lats1/2 thereby activating yap and taz transcription co-activators, which are oncoproteins repressed by lats1/2.	SIGNOR-198556
P18564	Q99704	2	binding	down-regulates activity	0.2	Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation	SIGNOR-257693
Q9P1W9	O00409	0	transcriptional regulation	down-regulates quantity by repression	0.297	CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis.	SIGNOR-261607
P08253	P20742	2	cleavage	down-regulates quantity by destabilization	0.329	The complex formation was confirmed by the use of 125I-labeled matrix metalloproteinase-2. The cleavage sites in the "bait" regions following formation of high-molecular-weight complexes of matrix metalloproteinases with the alpha-macroglobulins were determined by protein sequence analysis. Pregnancy zone protein was cleaved at Thr693-Tyr694 and alpha2-macroglobulin at Gly679-Leu680 and Arg696-Leu697 by matrix metalloproteinase-2. Matrix metalloproteinase-9 cleaved alpha2-macroglobulin at the same site as matrix metalloproteinase-2, but cleavage of pregnancy zone protein was at Leu753-Ser754.\|MMP-2 and MMP-9 cause a significant degradation of these bands and the background, a degradation which is prevented by both a2M and PZP.	SIGNOR-261796
Q92915	Q15858	2	binding	down-regulates activity	0.2	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-253425
P31431	Q92997	2	binding	up-regulates	0.247	Like other wnt co-receptors, syndecan 4 directly interacts with dvl during pcp 1.	SIGNOR-199638
P54646	P36956	1	phosphorylation	down-regulates	0.328	Here we demonstrate that ampk interacts with and directly phosphorylates sterol regulatory element binding proteins (srebp-1c and -2). Ser372	SIGNOR-173031
Q96GD4	Q8TF76	1	phosphorylation	up-regulates activity	0.2	Phosphorylation by Aurora B is required for full Haspin activity toward H3T3 in mitosis	SIGNOR-262657
P0DMV9	Q9HC29	2	binding	up-regulates quantity by stabilization	0.2	The molecular chaperone HSP70 binds to and stabilizes NOD2, an important protein involved in Crohn disease.	SIGNOR-252417
Q99102	P14921	0	transcriptional regulation	up-regulates quantity by expression	0.2	Through promoter screening, overexpressing methods and luciferase reporter studies, we found that transcription factors CREB, Ets-1, Elk-1 and STAT1 can positively regulate MUC4 expression at the promoter and mRNA level.	SIGNOR-254098
P27361	Q9BR01	1	phosphorylation	down-regulates	0.2	The phosphorylation of sult4a1 allows interaction with pin1, which then promotes degradation of the sulfotransferase.	SIGNOR-168248
O15111	Q9Y6Q9	1	phosphorylation	up-regulates	0.395	Herein, we report the successful identification of six functional in vivo src-3 phosphorylation sites.	SIGNOR-196953
Q9NYY1	Q6UXL0	2	binding	up-regulates	0.77	An IL-20 receptor was identified as a heterodimer of two orphan class II cytokine receptor subunits. Both receptor subunits are expressed in skin and are dramatically upregulated in psoriatic skin. Taken together, these results demonstrate a role in epidermal function and psoriasis for IL-20, a novel cytokine identified solely by bioinformatics analysis.	SIGNOR-151874
Q96PU5	Q9UI33	1	ubiquitination	down-regulates quantity by destabilization	0.288	The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).	SIGNOR-253462
P19784	Q00613	1	phosphorylation	up-regulates	0.348	Transcriptional activity and dna binding of heat shock factor-1 involve phosphorylation on threonine 142 by ck2.As hsf1 is activated by heat shock simultaneously with the nuclear translocation of the protein kinase ck2, we have investigated the role of ck2 in hsf1 activatio	SIGNOR-99606
Q9NTX7	O15169	1	ubiquitination	down-regulates quantity by destabilization	0.645	Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.	SIGNOR-263335
P51608	O75398	2	binding	up-regulates activity	0.2	We show that MeCP2 enhances Deaf1 binding to its HTR1A site and co-immunoprecipitates with Deaf1 in cells and brain tissue.To address the role of MeCP2 in HTR1A regulation in vivo, mice with conditional knockout of MeCP2 in adult 5-HT neurons (MeCP2 cKO) were generated. These mice exhibited increased 5-HT1A autoreceptor levels and function, consistent with MeCP2 enhancement of Deaf1 repression in 5-HT neurons.	SIGNOR-269063
P17612	Q15054	1	phosphorylation	down-regulates	0.2	In this study, we identified s458, located in the pcna-interacting protein (pip-box) motif of p68, as a phosphorylation site for pka. Phosphomimetic mutation of s458 resulted in a decrease in p68 affinity for pcna as well as the processivity of pol _.	SIGNOR-195203
P78352	Q9HBW1	2	binding	up-regulates activity	0.424	A possible function for the NGL–PSD-95 interaction is to couple trans-synaptic adhesion events to the recruitment of PSD-95 and other PSD-95-associated postsynaptic proteins. PSD-95 and liprin-α may be key synaptic scaffolding proteins that couple trans-synaptic adhesions to the assembly of synaptic proteins/vesicles	SIGNOR-264051
Q9GZY8	Q15139	0	phosphorylation	up-regulates activity	0.2	PKD directly phosphorylates MFF on serines 155, 172, and 275	SIGNOR-277559
P17612	P26599	1	phosphorylation	down-regulates activity	0.309	PKA directly phosphorylates PTB on conserved Ser-16, and PKA activation in PC12 cells induces Ser-16 phosphorylation. PTB carrying a Ser-16 to alanine mutation accumulates normally in the nucleus. However, export of this mutant protein from the nucleus is greatly reduced in heterokaryon shuttling assays. Conversely, hyperphosphorylation of PTB by coexpression with the catalytic subunit of PKA results in the accumulation of PTB in the cytoplasm.	SIGNOR-263149
Q8IWQ3	Q13131	1	phosphorylation	up-regulates	0.291	Ampka1 activators increased phosphorylation level and cytoplasmic localization (reduced nuclear/cytoplasmic ratio). Ampka1 activators reduced rna synthesis in the nucleoli.	SIGNOR-176594
Q01094	Q13547	2	binding	up-regulates	0.653	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-199952

P19784

Q9Y5B0

1

phosphorylation

down-regulates activity

0.374

We found that only phosphorylated FCP1 can physically interact with TFIIF. We set out to purify an FCP1 kinase from HeLa cells and identified casein kinase 2, which, surprisingly, displayed a negative effect on FCP1-associated activities.| Phosphorylation of FCP1 by CK2 Inhibits the Transcription Elongation Activity of FCP1. | Two in vivo phosphorylation sites within the C terminus of FCP1 at Ser-575 and Ser-740 were identified

SIGNOR-250986

Q9Y6Q9

P18848

2

binding

up-regulates activity

0.2

Mechanistically, Dyrk3 directly phosphorylated NCOA3 at Ser-1330, disrupting its binding to ATF4 and thereby causing the inhibition of ATF4 transcriptional activity.

SIGNOR-275452

P67775

P31314

2

binding

down-regulates activity

0.308

HOX11 also inhibited PP2A serine/threonine phosphatase activity concomitant with stimulation of the AKT/PKB signaling cascade.

SIGNOR-240719

P03372

O00459

2

binding

up-regulates

0.545

Recently, it has been known that er activates phosphatidylinositol-3-oh kinase (pi3k) through binding with the p85 regulatory subunit of pi3k.

SIGNOR-140473

P19838

O14757

0

phosphorylation

down-regulates

0.275

Taken together, the above findings suggest that chk1 phosphorylates p50 at s329 and further, that this phosphorylation blocks p50 dna binding.

SIGNOR-195208

P07949

P31749

1

phosphorylation

up-regulates

0.323

The PKB Y315 residue, which is known to be phosphorylated by Src tyrosine kinase, was also a major site of phosphorylation by RET/PTC. RET/PTC-mediated tyrosine phosphorylation results in the activation of PKB kinase activity

SIGNOR-252619

P50750

Q9H0D6

1

phosphorylation

up-regulates activity

0.278

Among the RNA processing factors phosphorylated by Cdk9 was the 5'-to-3' "torpedo" exoribonuclease Xrn2, required in transcription termination by Pol II, which we validated as a bona fide P-TEFb substrate in vivo and in vitro. Phosphorylation by Cdk9 or phosphomimetic substitution of its target residue, Thr439, enhanced enzymatic activity of Xrn2 on synthetic substrates in vitro.

SIGNOR-277194

Q9Y243

Q92934

1

phosphorylation

down-regulates

0.542

Ser-136 is the major phosphoacceptor site for akt;akt can weakly phosphorilate ser-155.

SIGNOR-81122

Q9UNE7

Q13485

1

polyubiquitination

down-regulates quantity by destabilization

0.396

We demonstrate that the coexpression of Smad1 and Smad4 with the CHIP protein results in the degradation of the Smad proteins through a ubiquitin-mediated process.

SIGNOR-272947

O75882

P42127

2

binding

up-regulates

0.391

Attractin is a low-affinity receptor for agouti protein, but not agrp, in vitro and in vivo.

SIGNOR-85496

P68400

P13569

1

phosphorylation

down-regulates

0.278

Cftr possesses two ck2 phosphorylation sites (s422 and t1471) the t1471 residue, previously described as a site for cftr phosphorylation by ck2 (25), seems to be critical for cftr turnover and processing.

SIGNOR-176627

P29275

P08754

2

binding

up-regulates activity

0.279

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-257152

P19484

P10619

1

transcriptional regulation

up-regulates quantity by expression

0.298

Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants

SIGNOR-276549

P36888

P06241

0

phosphorylation

up-regulates activity

0.292

FYN phosphorylates FLT3 on tyrosine residues (A\u2013B) COS1 cells were transfected with plasmids expressing FLT3 wild-type and FYN wild-type or mutants.|It was not completely unexpected that FYN associates wild-type FLT3 in the absence of ligand stimulation in COS-1 cells, as overexpression of wild-type FLT3 results in ligand independent activation of FLT3 (data not shown).

SIGNOR-279715

Q96P68

P09471

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-257243

P17612

P61224

1

phosphorylation

up-regulates

0.522

These results provide a mechanistic explanation for the differential effects of rap1 phosphorylation by pka on effector protein interaction. camp is one among several pathways leading to rap1 activation

SIGNOR-187410

P01375

P48736

2

binding

up-regulates

0.296

Tnf activates phosphatidylinositol-3-oh kinase (pi(3)k)

SIGNOR-70625

P09471

P08912

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-257009

Q9UKT4

Q9UJX3

2

binding

down-regulates

0.458

Emi1 can inhibit apc already activated by cdc20 or cdh1.

SIGNOR-113382

P01189

Q01726

2

binding

up-regulates activity

0.766

Alpha-melanocyte stimulating hormone (alpha-MSH) binds to melanocortin-1 receptor (MC1R) on melanocytes to stimulate pigmentation and modulate various cutaneous inflammatory responses.

SIGNOR-252370

Q8IZU9

O14936

2

binding

up-regulates activity

0.459

A Missense De Novo Variant in the CASK-interactor KIRREL3 Gene Leading to Neurodevelopmental Disorder with Mild Cerebellar Hypoplasia. KIRREL3 is a gene important for the central nervous system development-in particular for the process of neuronal migration, axonal fasciculation, and synaptogenesis-and colocalizes and cooperates in neurons with CASK gene.

SIGNOR-269078

Q9H1J7

O75581

2

binding

up-regulates

0.625

Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.

SIGNOR-131888

Q9P2K8

P05198

1

phosphorylation

down-regulates activity

0.914

Translation initiation factor 2α [eukaryotic translation initiation factor 2α (eIF2α)] kinase phosphorylates serine51 (Ser51) of eIF2α and downregulates cellular protein synthesis.

SIGNOR-246157

P05106

Q9Y490

2

binding

up-regulates activity

0.793

Over the past 10 years, the binding of talin to the cytoplasmic tail of integrin-β subunits has been established to have a key role in integrin activation. Binding of the phosphotyrosinebinding (PTB)-domain-like subdomain of the protein 4.1, ezrin, radixin, moesin (FERM) domain of talin to the conserved WxxxNP(I/L)Y motif of the β-integrin tail permits additional weaker interactions between talin and the membrane-proximal region of the tail that trigger integrin activation, probably through the disruption of inhibitory interactions between α- and β-subunit cytoplasmic tails.

SIGNOR-257625

P06730

O00571

2

binding

down-regulates activity

0.628

DDX3 is a human RNA helicase with plethoric functions. we identified translation initiation factor eukaryotic initiation factor 4E (eIF4E) as a DDX3-binding partner. Interestingly, DDX3 utilizes a consensus eIF4E-binding sequence YIPPHLR to interact with the functionally important dorsal surface of eIF4E in a similar manner to other eIF4E-binding proteins. Furthermore, cap affinity chromatography analysis suggests that DDX3 traps eIF4E in a translationally inactive complex by blocking interaction with eIF4G.

SIGNOR-269193

P49768

Q92542

2

binding

up-regulates

0.965

Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2.

SIGNOR-118852

P51843

Q9Y618

2

binding

up-regulates activity

0.393

The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes.

SIGNOR-271785

P29320

Q13153

1

phosphorylation

up-regulates activity

0.277

Etk kinase directly phosphorylates and activates PAK1 in response to estrogen.|We demonstrated that estrogen-activated Etk directly phosphorylated PAK1 on Tyr153.

SIGNOR-278398

P43487

P53350

0

phosphorylation

up-regulates activity

0.359

Here, we demonstrated in vitro and in vivo phosphorylation of RanBP1 by Plk1 as well as the importance of phosphorylation of RanBP1 in the interaction between Plk1 and Ran during early mitosis.

SIGNOR-279751

Q01718

P63092

2

binding

up-regulates activity

0.516

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-268694

O14763

P25490

0

transcriptional regulation

down-regulates quantity by repression

0.403

Depletion of FKBP51 impairs the acetylation status of YY1 and interferes with its binding on the DR5 promoter. The lack of the repressor activity of YY1 increases DR5 transcription and sensitizes melanoma cell to TRAIL-induced apoptosis.

SIGNOR-268793

P15248

Q01113

2

binding

up-regulates

0.751

Interleukin 9 (il-9) exerts its pleiotropic effects through the il-9 receptor (il-9r) complex, which consists of the il-9r alpha-chain, which determines the cytokine specificity, and the il-2 receptor gamma-chain

SIGNOR-73601

O75874

P36888

0

phosphorylation

up-regulates activity

0.424

Moreover, in an in vitro kinase assay, purified recombinant FLT3 (rFLT3) phosphorylated recombinant IDH2 R140Q mutant but did not alter its catalytic activity (Figure 1C), whereas rFLT3 phosphorylated mIDH1 protein and enhanced its catalytic activity

SIGNOR-267630

Q12933

P20333

2

binding

up-regulates activity

0.708

Our analysis indicates that traf1 and traf2 are associated with the cytoplasmic domain of tnf-r2 in a heterodimeric complex in which traf2 contacts the receptor directly.

SIGNOR-34645

O95405

Q15796

1

relocalization

up-regulates activity

0.908

Smad anchor for receptor activation (SARA) is known as Smad cofactor that interacts directly with Smad2/3 and functions to recruit Smad2/3 to the TGF-beta receptor.

SIGNOR-165786

Q00987

P06400

1

ubiquitination

down-regulates quantity by destabilization

0.667

In this study, we found that Mdm2, a ubiquitin ligase for p53, promoted ubiquitin-dependent degradation of pRB

SIGNOR-278530

P15924

Q99959

2

binding

up-regulates quantity by stabilization

0.787

In contrast to the proper membrane localization of PKP2 and DSP after cotransfection of both WT proteins, mutant PKP2 C796R protein was not able to interact with FLAG-DSP to enable assembly at the junctional plaque, indicating the requirement of functional PKP2 for DSP integration into the desmosome.

SIGNOR-261254

P84022

Q16539

0

phosphorylation

up-regulates activity

0.537

Smad3 was phosphorylated at both Ser203 and Ser207 in untreated MCF10CA1h cells and the p38 and ROCK inhibitors each down-regulated phosphorylation at these sites. we demonstrate that phosphorylation at Ser203 and Ser207 residues is required for the full transactivation potential of Smad3, and that these residues are targets of the p38 and Rho/ROCK pathways.

SIGNOR-250112

P06748

Q9P275

0

deubiquitination

up-regulates quantity by stabilization

0.39

USP36 deubiquitylated the nucleolar proteins nucleophosmin/B23 and fibrillarin, and stabilized them by counteracting ubiquitylation-mediated proteasomal degradation.

SIGNOR-272290

Q00535

O15516

1

phosphorylation

up-regulates

0.328

Cdk5 phosphorylates clock at the thr-451 and thr-461 residues in association with transcriptional activation of clock.

SIGNOR-203227

P45973

P68431

2

binding

up-regulates activity

0.2

A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing.

SIGNOR-264490

O14757

O60566

1

phosphorylation

up-regulates activity

0.447

Nonetheless, in our experimental system a Chk1-dependent BubR1 phosphorylation was also observed after Noc treatment.|Possible requirement of Chk1 in U2OS cells to activate the mitotic spindle checkpoint proteins Mad2 and BubR1.

SIGNOR-280223

P55064

P17612

0

phosphorylation

up-regulates activity

0.2

AQP5 can be directly phosphorylated by PKA at Ser 156 |Our data hint at a mechanism whereby phosphorylation of Ser 156 in AQP5 increases its membrane localization, thereby enhancing cancer cell proliferation.

SIGNOR-272088

Q9H2X6

P15923

1

phosphorylation

down-regulates activity

0.2

This result provides a mechanistic explanation for the context-dependent function of HIPK2 in Wnt signaling

SIGNOR-279193

Q16566

P49841

1

phosphorylation

down-regulates activity

0.263

CAMK4 phosphorylates GSK3\u03b2 at serine 9, which leads to its inactivation. xref Accordingly, we examined the levels of phosphorylated GSK3\u03b2 at serine 9 (pGSK3\u03b2-ser9) in podocytes exposed to IgG from TG patients and calculated the ratio of pGSK3\u03b2-ser9 to total GSK3\u03b2.

SIGNOR-279142

Q13627

P08151

1

phosphorylation

up-regulates activity

0.514

Here, we have used an in vitro kinase assay and phospho-peptide mass spectrometry analysis to identify site(s) of direct phosphorylation of GLI1 by DYRK1A and have determined that DYRK1A phosphorylates GLI1 at Ser408 within its nuclear localization sequence.|The kinase DYRK1A (dual-specificity tyrosine phosphorylation regulated kinase 1a) has been shown to activate GLI1 via a phosphorylation event, leading to the translocation of GLI1 from the cytoplasm to the nucleus .

SIGNOR-278930

Q96S66

A0A0B4J2F0

2

binding

up-regulates activity

0.2

The PIGBOS microprotein interacts with the ER protein CLCC1. PIGBOS localizes to the mitochondrial outer membrane where itinteracts with the ER protein CLCC1 at ER–mitochondria contact sites. PIGBOS-CLCC1 interaction is necessary for PIGBOS function

SIGNOR-261040

P17252

P08567

1

phosphorylation

up-regulates

0.28

To determine the role of pkc-dependent phosphorylation in pleckstrin function, we mapped the phosphorylation sites in vivo of wild-type and site-directed mutants of pleckstrin expressed in cos cells. Phosphorylation was found to occur almost exclusively on ser-113 and ser-117. Replacing all these sites with glycine decreased phosphorylation by > 90% and reduced pleckstrin's ability to inhibit phosphoinositide hydrolysis by as much as 80%.

SIGNOR-40048

P56705

O75197

2

binding

up-regulates

0.649

Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.

SIGNOR-131832

P27361

P43364

1

phosphorylation

up-regulates

0.3

Mage-11 ser-174 appears to be a post-translational regulatory site phosphorylated by erk1, based on the inhibitory effect of the s174a mutation in the context of shorter ar nh2-terminal fragments (19), and the greater transcriptional activity of gal-mage-11 fusion proteins containing the s174d phosphomimetic.

SIGNOR-188466

P61011

Q01130

2

binding

up-regulates activity

0.341

We have now demonstrated that p54 interacts not only with SC35 and ASF/SF2 but also with U2AF. Pairwise interactions between p54 and other RS domain-containing spliceosomal proteins in comparison with SC35 and ASF/SF2 as detected by the yeast two-hybrid interaction assay. . It is conceivable that p54 can mediate 59 and 39 splice site interaction by interacting directly with U2AF65 associated with the 39 splice site and at the same time interact with other SR proteins, such as ASF/SF2 and SC35, which in turn interact with U1-70K. In this scenario, p54 is different from SC35 or ASF/SF2 in that it cannot directly interact with the 59 component (U1-70K) but can interact with the protein associated with the 39 splice site (U2AF65).

SIGNOR-261160

Q9Y6W8

O75144

2

binding

up-regulates activity

0.2

ICOSL expression is largely restricted to professional antigen-presenting cells (APCs), including B cells [in which ICOSL is regulated by BAFFR and non-canonical NFκB signaling (20)], macrophages, and dendritic cells (DCs) (12, 17, 21, 22), but is also expressed by certain endothelial cells (23) and lung epithelium

SIGNOR-272497

P04083

P25089

2

binding

up-regulates activity

0.618

We show that the mimetic N-terminal annexin 1 peptide Ac1-25 is able to activate and desensitize not only FPR but also FPRL1 and FPRL2.

SIGNOR-259438

P14316

Q8IU81

2

binding

up-regulates activity

0.692

We have identified two novel proteins that interact specifically with the C-terminal repression domain of Interferon Regulatory Factor-2 (IRF-2). These proteins, which we term IRF-2 binding proteins 1 and 2 (IRF-2BP1 and IRF-2BP2, the latter having two splicing isoforms, A and B), are nuclear proteins, and have the properties of IRF-2-dependent transcriptional co-repressors that can inhibit both enhancer-activated and basal transcription in a manner that is not dependent upon histone deacetylation.

SIGNOR-224045

P29353

Q05655

0

phosphorylation

up-regulates

0.569

Pkc delta phosphorylates p52shca at ser29 to regulate erk activation in response to h2o2.

SIGNOR-149398

P41145

P63096

2

binding

up-regulates activity

0.475

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-256710

P49841

Q12888

1

phosphorylation

up-regulates activity

0.283

Based on these observations, we hypothesized that the IR induced GSK3beta nuclear translocation may activate 53BP1 via phosphorylation at the S/T-Q motif.|Importantly, our in vivo and in vitro data clearly indicated that GSK3\u03b2 induced the phosphorylation of 53BP1 at the Ser166 site.

SIGNOR-278226

P08236

Q9NR19

0

transcriptional regulation

up-regulates quantity by expression

0.262

Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants

SIGNOR-276554

Q15642

Q99996

2

binding

up-regulates activity

0.512

Mechanistically, AKAP-9 interacted with cdc42 interacting protein 4 (CIP4) and regulated its expression. CIP4 levels were interrelated to the AKAP-9 level in CRC cells. Functionally, AKAP-9 was essential for TGF-β1-induced epithelial-mesenchymal transition of CRC cells, and CIP4 played a critical role in mediating the function of AKAP-9. Importantly, CIP4 expression was significantly up-regulated in human CRC tissues.|Co-immunoprecipitation assay revealed that AKAP-9 and CIP4 physically interacted with each other in Lovo and HT29 cells (Fig. 4B and C).

SIGNOR-260303

P02775

P35372

1

chemical inhibition

down-regulates activity

0.385

Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors.

SIGNOR-258413

P99999

O14727

2

binding

up-regulates activity

0.792

During apoptosis, Apaf-1 binds to cytochrome c and in the presence of ATP/dATP forms an apoptosome, leading to the recruitment and activation of the initiator caspase, caspase-9.

SIGNOR-135384

Q9Y2G2

P55211

2

binding

down-regulates

0.425

Tucan is a recently identified card-containing protein that can complex with caspase-9 and prevent cytochrome c-induced caspase activation.

SIGNOR-146663

P27361

P53805

1

phosphorylation

up-regulates activity

0.38

Consensus phosphorylation sites for p42/44 MAPK and GSK-3 are present in the SP repeat of MCIP1 at serine 112 and serine 108, respectively |Several endogenous proteins are capable of inhibiting the catalytic activity of calcineurin. Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these proteins on the basis of its pattern of expression and its function in a negative feedback loop to regulate calcineurin activity. Here we show that MCIP1 can be phosphorylated by MAPK and glycogen synthase kinase-3 and that phosphorylated MCIP1 is a substrate for calcineurin.

SIGNOR-249478

Q13523

Q9Y2Y9

1

phosphorylation

down-regulates

0.342

Using yeast two-hybrid screening of a human thymus cdna library, prp4, a serine/threonine protein kinase, was identified as a klf13-binding protein...coexpression of prp4 and klf13 increases nuclear localization of klf13 and ccl5 transcription.

SIGNOR-154951

P63096

P46663

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-257036

Q16581

P35626

0

phosphorylation

down-regulates activity

0.2

These findings suggest that in agonist-stimulated mast cells GRK2 and GRK3 may phosphorylate C3aR at the same or distinct sites to promote receptor desensitization.

SIGNOR-279781

P51965

P29372

2

binding

up-regulates activity

0.2

Here we report that MID1 catalyzes the in vitro ubiquitination of the catalytic subunit of PP2A (PP2Ac) in the absence of alpha4. In the presence of alpha4, the level of PP2Ac ubiquitination is reduced.The high molecular weight smear pattern was not as obvious, suggesting that domains within the C-terminal half of MID1 may contribute to the polyubiquitination of PP2Ac. We observed that PP2Ac was ubiquitinated in the presence of UbcH5a-c and UbcH6, similar to results obtained with MID1-catalyzed ubiquitination of alpha4 (Figure 2E)

SIGNOR-271929

Q13105

P51610

2

binding

down-regulates activity

0.344

We show here that HCF-1 directly binds to the Myc-interacting protein Miz-1. HCF-1 Represses Gal4-Miz-1-mediated Transcriptional Activation

SIGNOR-223590

P02671

P20702

2

binding

up-regulates

0.387

To map the binding sites for four distinct ligands for mac-l: ic3b, fibrinogen, icam-1. __the i domain on the ot chain of mac-1 is an important recognition site for all four ligands.

SIGNOR-31320

Q12774

P12931

0

phosphorylation

up-regulates activity

0.465

Arhgef5 was tyrosine-phosphorylated by Src and bound to Src to positively regulate its activity.|Using an inducible system for Src activation, we found that Src induced podosome formation depends upon the Src SH3 domain, and identified Arhgef5 as a Src SH3 binding protein.

SIGNOR-279571

Q8WYQ5

P00519

0

phosphorylation

up-regulates activity

0.2

The kinase ABL phosphorylates the microprocessor subunit DGCR8 to stimulate primary microRNA processing in response to DNA damage. When coexpressed in HEK293T cells, ABL phosphorylated DGCR8 at Tyr(267).

SIGNOR-262604

Q15172

P17252

0

phosphorylation

down-regulates activity

0.341

In this study, we identified a novel phosphorylation site at Ser(41) of B56α. This phosphoamino acid residue was efficiently phosphorylated in vitro by PKCα.

SIGNOR-276603

Q15109

P06702

2

binding

up-regulates activity

0.346

RAGE and TLR4 are well-characterized S100A8 and S100A9 receptors and expressed in AML cells Once secreted, S100A8 and S100A9 induce immune and inflammatory responses9 through interaction with receptors such as Toll-like receptor 4 (TLR4), receptor for advanced glycation end-product (RAGE), and CD33

SIGNOR-261920

O95551

P36896

0

phosphorylation

up-regulates activity

0.28

ALK4 phosphorylated TTRAP in vitro (Fig. 6A). The band migrating at the position of TTRAP was excised and analyzed by LC-MS/MS. One TTRAP peptide was phosphorylated either on T88 and T92, or on T92 only (Fig. 6B).We tested in vivo phosphorylation of Strep-TTRAP by co-expression with mouse Alk4 in HEK293T cells, and affinity-purified TTRAP. In this preparation TTRAP-specific peptides were reproducibly found in both the singly (T92) and doubly phosphorylated form (T88/T92). mutant TTRAPT88A,T92A is not able to rescue the TtrapMO phenotype, suggesting that phosphorylation of Ttrap on Thr88 and Thr92 is essential for Ttrap function.

SIGNOR-262612

Q15118

Q16513

1

phosphorylation

up-regulates activity

0.338

PDK1 phosphorylates the PRKs at their conserved activation loop threonines (Thr-774 and Thr-816 for PRK1 and PRK2, respectively) both in vitro and in vivo.

SIGNOR-250265

Q96PU5

Q9NRA0

1

ubiquitination

down-regulates quantity by destabilization

0.2

In this study, we found that NEDD4L interacted with SphK2 to ubiquitinate SphK2 protein.|NEDD4L Mediates the Degradation of SphK2 Protein Through the Ubiquitin-Proteasomal Pathway.

SIGNOR-278660

Q9H228

P08754

2

binding

up-regulates activity

0.385

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

SIGNOR-256819

O95136

Q03113

2

binding

up-regulates

0.47

Serum-borne lysophosphatidic acid (lpa) and sphingosine 1-phosphophate (s1p) act through g12/13-coupled receptors to inhibit the hippo pathway kinases lats1/2 thereby activating yap and taz transcription co-activators, which are oncoproteins repressed by lats1/2.

SIGNOR-198556

P18564

Q99704

2

binding

down-regulates activity

0.2

Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation

SIGNOR-257693

Q9P1W9

O00409

0

transcriptional regulation

down-regulates quantity by repression

0.297

CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis.

SIGNOR-261607

P08253

P20742

2

cleavage

down-regulates quantity by destabilization

0.329

The complex formation was confirmed by the use of 125I-labeled matrix metalloproteinase-2. The cleavage sites in the "bait" regions following formation of high-molecular-weight complexes of matrix metalloproteinases with the alpha-macroglobulins were determined by protein sequence analysis. Pregnancy zone protein was cleaved at Thr693-Tyr694 and alpha2-macroglobulin at Gly679-Leu680 and Arg696-Leu697 by matrix metalloproteinase-2. Matrix metalloproteinase-9 cleaved alpha2-macroglobulin at the same site as matrix metalloproteinase-2, but cleavage of pregnancy zone protein was at Leu753-Ser754.|MMP-2 and MMP-9 cause a significant degradation of these bands and the background, a degradation which is prevented by both a2M and PZP.

SIGNOR-261796

Q92915

Q15858

2

binding

down-regulates activity

0.2

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-253425

P31431

Q92997

2

binding

up-regulates

0.247

Like other wnt co-receptors, syndecan 4 directly interacts with dvl during pcp 1.

SIGNOR-199638

P54646

P36956

1

phosphorylation

down-regulates

0.328

Here we demonstrate that ampk interacts with and directly phosphorylates sterol regulatory element binding proteins (srebp-1c and -2). Ser372

SIGNOR-173031

Q96GD4

Q8TF76

1

phosphorylation

up-regulates activity

0.2

Phosphorylation by Aurora B is required for full Haspin activity toward H3T3 in mitosis

SIGNOR-262657

P0DMV9

Q9HC29

2

binding

up-regulates quantity by stabilization

0.2

The molecular chaperone HSP70 binds to and stabilizes NOD2, an important protein involved in Crohn disease.

SIGNOR-252417

Q99102

P14921

0

transcriptional regulation

up-regulates quantity by expression

0.2

Through promoter screening, overexpressing methods and luciferase reporter studies, we found that transcription factors CREB, Ets-1, Elk-1 and STAT1 can positively regulate MUC4 expression at the promoter and mRNA level.

SIGNOR-254098

P27361

Q9BR01

1

phosphorylation

down-regulates

0.2

The phosphorylation of sult4a1 allows interaction with pin1, which then promotes degradation of the sulfotransferase.

SIGNOR-168248

O15111

Q9Y6Q9

1

phosphorylation

up-regulates

0.395

Herein, we report the successful identification of six functional in vivo src-3 phosphorylation sites.

SIGNOR-196953

Q9NYY1

Q6UXL0

2

binding

up-regulates

0.77

An IL-20 receptor was identified as a heterodimer of two orphan class II cytokine receptor subunits. Both receptor subunits are expressed in skin and are dramatically upregulated in psoriatic skin. Taken together, these results demonstrate a role in epidermal function and psoriasis for IL-20, a novel cytokine identified solely by bioinformatics analysis.

SIGNOR-151874

Q96PU5

Q9UI33

1

ubiquitination

down-regulates quantity by destabilization

0.288

The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).

SIGNOR-253462

P19784

Q00613

1

phosphorylation

up-regulates

0.348

Transcriptional activity and dna binding of heat shock factor-1 involve phosphorylation on threonine 142 by ck2.As hsf1 is activated by heat shock simultaneously with the nuclear translocation of the protein kinase ck2, we have investigated the role of ck2 in hsf1 activatio

SIGNOR-99606

Q9NTX7

O15169

1

ubiquitination

down-regulates quantity by destabilization

0.645

Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.

SIGNOR-263335

P51608

O75398

2

binding

up-regulates activity

0.2

We show that MeCP2 enhances Deaf1 binding to its HTR1A site and co-immunoprecipitates with Deaf1 in cells and brain tissue.To address the role of MeCP2 in HTR1A regulation in vivo, mice with conditional knockout of MeCP2 in adult 5-HT neurons (MeCP2 cKO) were generated. These mice exhibited increased 5-HT1A autoreceptor levels and function, consistent with MeCP2 enhancement of Deaf1 repression in 5-HT neurons.

SIGNOR-269063

P17612

Q15054

1

phosphorylation

down-regulates

0.2

In this study, we identified s458, located in the pcna-interacting protein (pip-box) motif of p68, as a phosphorylation site for pka. Phosphomimetic mutation of s458 resulted in a decrease in p68 affinity for pcna as well as the processivity of pol _.

SIGNOR-195203

P78352

Q9HBW1

2

binding

up-regulates activity

0.424

A possible function for the NGL–PSD-95 interaction is to couple trans-synaptic adhesion events to the recruitment of PSD-95 and other PSD-95-associated postsynaptic proteins. PSD-95 and liprin-α may be key synaptic scaffolding proteins that couple trans-synaptic adhesions to the assembly of synaptic proteins/vesicles

SIGNOR-264051

Q9GZY8

Q15139

0

phosphorylation

up-regulates activity

0.2

PKD directly phosphorylates MFF on serines 155, 172, and 275

SIGNOR-277559

P17612

P26599

1

phosphorylation

down-regulates activity

0.309

PKA directly phosphorylates PTB on conserved Ser-16, and PKA activation in PC12 cells induces Ser-16 phosphorylation. PTB carrying a Ser-16 to alanine mutation accumulates normally in the nucleus. However, export of this mutant protein from the nucleus is greatly reduced in heterokaryon shuttling assays. Conversely, hyperphosphorylation of PTB by coexpression with the catalytic subunit of PKA results in the accumulation of PTB in the cytoplasm.

SIGNOR-263149

Q8IWQ3

Q13131

1

phosphorylation

up-regulates

0.291

Ampka1 activators increased phosphorylation level and cytoplasmic localization (reduced nuclear/cytoplasmic ratio). Ampka1 activators reduced rna synthesis in the nucleoli.

SIGNOR-176594

Q01094

Q13547

2

binding

up-regulates

0.653

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-199952