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
P17096	P06493	0	phosphorylation	down-regulates	0.384	Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation.	SIGNOR-158604
Q08334	Q8IZI9	2	binding	up-regulates	0.848	Il-28 and il-29 interacted with a heterodimeric class ii cytokine receptor that consisted of il-10 receptor beta (il-10rbeta) and an orphan class ii receptor chain, designated il-28ralpha.	SIGNOR-96246
Q5VT25	P60953	2	binding	up-regulates activity	0.792	Myotonic dystrophy kinase-related Cdc42-binding kinase acts as a Cdc42 effector in promoting cytoskeletal reorganization\|MRCK alpha and Cdc42V12 colocalize, particularly at the cell periphery in transfected HeLa cells. Microinjection of plasmid encoding MRCK alpha resulted in actin and myosin reorganization.	SIGNOR-262593
Q92997	Q8IZQ1	0	relocalization	down-regulates quantity by destabilization	0.251	Our data taken together with the known role of ALFY in autophagy, demonstrate specific targeting and autophagy-mediated removal of DVL3 by hALFY.	SIGNOR-266793
O94813	Q8NFU7	0	transcriptional regulation	up-regulates quantity by expression	0.2	Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9.	SIGNOR-259093
O43186	Q96SL8	2	binding	down-regulates activity	0.455	Interaction of Fiz1 and NRL-leucine zipper was validated by GST pulldown assays and co-immunoprecipitation from bovine retinal nuclear extracts. Fiz1 suppressed NRL- but not CRX-mediated transactivation of rhodopsin promoter activity in transiently transfected CV1 cells.	SIGNOR-223799
P52566	Q9NYL2	0	phosphorylation	down-regulates activity	0.2	In the present study, we provide evidence that ZAK serves as a RhoGDIbeta kinase, and demonstrate the phosphorylation of RhoGDIbeta by ZAK in vitro, as well as the physical association between ZAK and RhoGDIbeta.\|These two proteins could negatively regulate one another such that ZAK suppresses RhoGDIbeta functions through phosphorylation and RhoGDIbeta counteracts the effects of ZAK by physical interaction.	SIGNOR-279633
Q04760	P21802	0	phosphorylation	up-regulates activity	0.2	We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).	SIGNOR-276184
P17542	P62256	1	transcriptional regulation	up-regulates quantity by expression	0.326	Tal1 expression activated UBE2H expression, whereas Tal1 knock-down reduced UBE2H expression and ubiquitin transfer activity.\|Binding of Tal1 to UBE2H was confirmed by chromatin immunoprecipitation.	SIGNOR-269000
Q04760	P22607	0	phosphorylation	up-regulates activity	0.2	We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).	SIGNOR-276181
O15198	Q13485	1	phosphorylation	up-regulates	0.685	Whereas alk5 signalling is mediated by phosphorylation of smad2 and smad3 proteins, alk1 signalling is mediated by smad1, smad5, and smad8. Activated smads form a complex with the common smad (co-smad; smad4 in mammals) and shuttle into the nucleus.	SIGNOR-168740
Q96J92	O95747	1	phosphorylation	up-regulates activity	0.48	In addition, WNK4 phosphorylates and activates Ste20-type kinases SPAK and OSR1, which in turn phosphorylate and activate NCC [ xref ; xref ].\|Later studies also indicate that WNK4 phosphorylates and activates Ste20-type kinases SPAK and OSR1, which in turn phosphorylates and activates NCC ; ].	SIGNOR-278389
Q16549	P28324	1	phosphorylation	up-regulates	0.2	In contrast, the tcf sap-1a is efficiently phosphorylated by p38 map kinase in vitro and in vivo on the homologous residues ser381 and ser387	SIGNOR-47771
P11308	O15550	0	transcriptional regulation	down-regulates quantity by repression	0.2	Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase	SIGNOR-260033
P68400	P03372	1	phosphorylation	down-regulates	0.246	Additionally protein kinase ck2 was identified as a kinase that phosphorylated eralpha at s282 and s559 s282 and s559 represent the second and third sites of er_ regulation by ck2. Remarkably, mutation of s282 or s559 to alanine resulted in near opposite functional effects on er_ as compared to mutation of s167 to alanine. Er_ ligand independent transcriptional activity was markedly enhanced upon mutation of s282 and s559 to alanine	SIGNOR-162653
P35372	P02775	0	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
Q08209	Q12968	1	dephosphorylation	up-regulates	0.538	Calcineurin directly dephosphorylates nfat resulting in the nuclear import of nfat.	SIGNOR-176376
P54252	O95155	0	polyubiquitination	down-regulates quantity by destabilization	0.578	Mammalian E4B (UFD2a), a ubiquitin chain assembly factor (E4), copurified with the polyubiquitylation activity for ataxin-3. E4B interacted with, and thereby mediated polyubiquitylation of, ataxin-3. Collectively, these data suggest that E4B promotes the degradation of ataxin-3, and that this effect surmounts the stabilization of ataxin-3 conferred by expansion of the polyglutamine tract.	SIGNOR-271502
P49683	P08754	2	binding	up-regulates activity	0.278	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-256837
P01019-PRO_0000032458	P50052	2	binding	up-regulates activity	0.2	Ang II initiates most of the RAS-attributed physiologic effects through selective interactions with G-proteincoupled Ang II type 1 (AT1) or type 2 (AT2) receptors and subsequent activation of distinct intra cellular signaling pathways	SIGNOR-260237
Q9H0K1	Q53ET0	1	phosphorylation	down-regulates	0.743	Phosphorylation on the ser171 residue of crtc2 by ampk and ampk-related kinases, including the salt-inducible kinases (siks), is critical for determining the activity, cellular localization, and degradation of crtc2	SIGNOR-142218
Q05655	Q16658	1	phosphorylation	down-regulates activity	0.324	Phosphorylation of human fascin inhibits its actin binding and bundling activities.	SIGNOR-248944
Q12772	Q8WU17	0	ubiquitination	down-regulates quantity	0.477	Induction of TRC8 destabilized the precursor forms of the transcription factors SREBP-1 and SREBP-2. TRC8 destablizes SREBP precursors in a RING and proteasome-dependent manner	SIGNOR-271958
Q13253	Q13873	2	binding	down-regulates activity	0.588	Noggin binds the domain that is re-quired for bmp-7 to interact with bmp type i and type ii receptors.Noggin Inhibits bmp by blocking the molecular interfaces of the binding epitopes for both type i and type ii receptors (pmid 12478285)	SIGNOR-195612
Q16828	Q13164	1	dephosphorylation	down-regulates activity	0.646	However, whilst the interaction itself might be difficult to monitor, DUSP6 should still be able to promote the de-phosphorylation of ERK5 in cells if it is an ERK5 phosphatase.To test this HEK293 cells were transiently transfected with HA-ERK2 or HA-ERK5 together with EGFP-MEK1E (a constitutively active version of MEK1) or EGFP-MEK5D (a constitutively active version of MEK5).\|Whilst one can envisage scenarios in which the interaction between DUSPs and their substrates might be transient, DUSP6 should still be able to promote the de-phosphorylation and inactivation of ERK5.	SIGNOR-277007
Q92973	O15534	1	relocalization	up-regulates activity	0.268	The non-classical nuclear import carrier Transportin 1 modulates circadian rhythms through its effect on PER1 nuclear localization	SIGNOR-262102
Q16204	P27361	0	phosphorylation	up-regulates activity	0.367	We have characterized the H4(D10S170) gene product, showing that it is a ubiquitously expressed 55 KDa nuclear and cytosolic protein that is phosphorylated following serum stimulation. This phosphorylation was found to depend on mitogen-activated protein kinase (MAPK) Erk1/2 activity and to be associated to the relocation of H4(D10S170) from the nucleus to the cytosol. S244 is the major target residue of ERK1	SIGNOR-276003
O75444	P14921	2	binding	down-regulates	0.425	Full-length c-maf binds to the c-myb and ets-1. / c-maf inhibits c-myb and ets-1 transcriptional activity.	SIGNOR-56808
Q9NUX5	O14746	2	binding	up-regulates	0.673	We find that tpp1 and pot1 form a complex with telomeric dna that increases the activity and processivity of the human telomerase core enzyme.	SIGNOR-152327
O75962	P43146	2	binding	up-regulates quantity	0.606	TrioY2622 is required for both netrin-1-induced activation of Rac1 and enhanced association with DCC. Phosphorylation of Trio at Tyr2622 participates in maintaining the level of surface DCC at the growth cone plasma membrane leading to axon outgrowth. Therefore, we propose that TrioY2622 is essential for the proper assembly and stability of the DCC/Trio signaling complex at the cell surface of growth cones in order to mediate netrin-1-induced cortical axon outgrowth.	SIGNOR-273856
P43115	P00533	1	relocalization	up-regulates quantity	0.332	These results demonstrate that PGE2 -mediated EGFR nuclear translocation requires the EP3 receptor.	SIGNOR-278884
P50148	P50406	2	binding	up-regulates activity	0.344	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-257340
P19086	P30542	2	binding	up-regulates activity	0.335	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-257092
P62140	Q00987	1	dephosphorylation	up-regulates quantity by stabilization	0.2	Three phosphorylation sites identified are Ser342, Ser367, and Ser403. In the present study, we identify protein phosphatase 1 (PP1) as a negative regulator in the p53 signaling pathway. PP1 directly interacts with Mdmx and specifically dephosphorylates Mdmx at Ser367. The dephosphorylation of Mdmx increases its stability and thereby inhibits p53 activity.	SIGNOR-248577
Q9UL54	P52564	2	binding	up-regulates activity	0.649	Cotransfection experiments suggested that tao2 selectively activates mek3 and mek6 but not meks 1, 4, or 7.	SIGNOR-70950
P38936	P14635	2	binding	down-regulates	0.829	P21-mediated degradation of cyclin b1 in response to dna damage is necessary for the maintenance of g2 cell cycle arrest.	SIGNOR-183498
Q86XR7	Q02156	0	phosphorylation	up-regulates	0.573	Here we show that tram is transiently phosphorylated by pkcepsilon on serine-16 our study provides a possible target for these molecules in lps signaling. Dag may activate pkc?, Leading to the phosphorylation and activation of tram.	SIGNOR-146991
P04150	Q9Y616	1	transcriptional regulation	up-regulates quantity	0.36	We show that glucocorticoids and non-typeable Haemophilus influenzae synergistically upregulate IRAK-M expression via mutually and synergistically enhancing p65 and glucocorticoid receptor binding to the IRAK-M promoter	SIGNOR-259287
Q9GZY8	Q13131	0	phosphorylation	up-regulates activity	0.2	A screen for substrates of AMPK identified mitochondrial fission factor (MFF), a mitochondrial outer-membrane receptor for DRP1, the cytoplasmic guanosine triphosphatase that catalyzes mitochondrial fission.	SIGNOR-245953
P45984	P31947	1	phosphorylation	down-regulates	0.2	Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-189	SIGNOR-124027
P49841	Q13418	0	phosphorylation	down-regulates activity	0.69	ILK can also directly phosphorylates GSK-3\u03b2 at Ser 9, inactivate it, and lead to activation of some transcription factors [ ].\|ILK knockdown activates GSK-3beta.	SIGNOR-278252
O95071	Q92547	1	polyubiquitination	down-regulates quantity by destabilization	0.462	Using an in vitro reconstitution, specific E2 (ubiquitin-conjugating) enzymes (human UbcH4, UbcH5B, and UbcH5C) transferred ubiquitin molecules to hHYD, leading to the ubiquitination of TopBP1. TopBP1 was usually ubiquitinated and degraded by the proteosome, whereas X-irradiation diminished the ubiquitination of TopBP1 probably via the phosphorylation, resulting in the stable colocalization of up-regulated TopBP1 with gamma-H2AX nuclear foci in DNA breaks.	SIGNOR-272667
Q9NYL2	P52566	1	phosphorylation	down-regulates activity	0.2	In the present study, we provide evidence that ZAK serves as a RhoGDIbeta kinase, and demonstrate the phosphorylation of RhoGDIbeta by ZAK in vitro, as well as the physical association between ZAK and RhoGDIbeta.\|These two proteins could negatively regulate one another such that ZAK suppresses RhoGDIbeta functions through phosphorylation and RhoGDIbeta counteracts the effects of ZAK by physical interaction.	SIGNOR-279633
Q9UKB1	P63208	2	binding	up-regulates	0.801	The scf is composed of skp1, cdc53/cul1, and a specificity-conferring f-box protein. F-box proteins contain two domains, an f-box motif that binds skp1 and allows assembly into skp1/cdc53 complexes, and a second proteinprotein interaction domain that interacts specifically with one or more target proteins. Cdc53/cul1, in turn, interacts with both the e2 and the skp1/f-box protein complex.	SIGNOR-64505
P23470	O60674	1	dephosphorylation	down-regulates activity	0.287	Deeper examination shows that JAKs are critically involved in integrin-mediated monocyte adhesion and that PTPRG activation leads to JAK2 dephosphorylation on the critical 1007–1008 phosphotyrosine residues, implying JAK2 inhibition and thus explaining the antiadhesive role of PTPRG.	SIGNOR-254690
P31751	P30405	1	phosphorylation	up-regulates activity	0.2	In turn, mitochondrial Akt2 phosphorylates Ser31 in cyclophilin D (CypD), a regulator of organelle functions. Akt2-phosphorylated CypD supports mitochondrial bioenergetics and opposes tumor cell death, conferring resistance to PI3K therapy.	SIGNOR-276875
P56693	P49841	0	phosphorylation	down-regulates quantity	0.406	Besides, GSK3\u03b2 phosphorylates SOX10 at CPD domain and facilitates Fbxw7\u03b1-mediated SOX10 degradation.\|Besides, GSK3beta phosphorylates SOX10 at CPD domain and facilitates Fbxw7alpha mediated SOX10 degradation.	SIGNOR-279617
Q13017	Q13882	0	phosphorylation	up-regulates	0.2	Breast tumor kinase phosphorylates p190rhogap to regulate rho and ras and promote breast carcinoma growth, migration, and invasion. Brk phosphorylates p190 at the y(1105) residue both in vitro and in vivo, thereby promoting the association of p190 with p120rasgap (p120). As a consequence, brk stimulates p190 and attenuates p120 functions, leading to rhoa inactivation and ras activation, respectively.	SIGNOR-181452
Q13485	O43541	2	binding	down-regulates activity	0.574	On the other hand, Smad6 competes with R-Smad and forms a non-functional complex with Smad4, which will inhibit BMP signaling in bone formation. Smad6 is involved in a negative feedback loop regulating BMP signaling and is required to limit BMP signaling during endochondral bone formation.	SIGNOR-195648
P08174	P48960	2	binding	up-regulates	0.2	This interaction may facilitate cell activation and migration through the blood-brain barrier. In addition, cd97-cd55 interactions in the parenchyma of the brain may contribute to the inflammation.	SIGNOR-95458
Q86VZ6	P49116	2	binding	down-regulates	0.453	Tip27 interacts specifically with tak1 / tip27 functions as a tak1-selective repressor	SIGNOR-127900
P15923	P15172	2	binding	up-regulates activity	0.806	In addition we demonstrate that myod, in conjunction with e12/e47-like proteins, is functioning as a regulatory nodal point for activation of several other downstream muscle regulators.	SIGNOR-20540
P48729	P12830	1	phosphorylation	down-regulates activity	0.312	Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts\|CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846	SIGNOR-274045
Q9BUB5	O00141	0	phosphorylation	down-regulates activity	0.2	We show that SGK1 phosphorylates MNK1 at a conserved site, which represses its activity.	SIGNOR-277357
P13500	O75626	0	transcriptional regulation	down-regulates quantity by repression	0.2	Blimp-1 binds to the proinflammatory cytokine/chemokine genes, Il-6 and Ccl2, and negatively regulates their expression.	SIGNOR-271679
P15172	Q13547	2	binding	down-regulates	0.547	Interaction of myod with hdac1 in undifferentiated myoblasts mediates repression of muscle-specific gene expression.	SIGNOR-111243
P45984	Q12968	1	relocalization	down-regulates	0.711	Jnks directly phosphorylate nuclear factor of activated t-cell (nfat) transcription factors, thus antagonizing the effects of calcium-regulated signaling through the protein phosphatase calcineurin.	SIGNOR-103360
P10636-2	Q02156	0	phosphorylation	down-regulates activity	0.271	We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.	SIGNOR-275444
P21731	O95837	2	binding	up-regulates activity	0.47	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-257023
P12830	P56545	0	transcriptional regulation	down-regulates quantity by repression	0.381	Overexpression of the CtBP2 protein enhanced the repression activity of the E-cadherin promoter in a dose-dependent manner, whereas overexpression of ataxin-1 increased the activity of the E-cadherin promoter in a dose-dependent manner	SIGNOR-261578
P41146	P08754	2	binding	up-regulates activity	0.458	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-256865
O60928	P17612	0	phosphorylation	up-regulates	0.2	Pka activation induced an increase of kir7.1 currents. This effect was absent in mutant kir7.1 channels lacking pka consensus site (287)s	SIGNOR-181859
P55085	P50148	2	binding	up-regulates activity	0.406	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257300
Q13177	P00519	1	phosphorylation	down-regulates	0.415	The interaction of c-abl with the abl interactor protein abi2 is shown to be negatively regulated by phosphorylation of serines 637 and 638. These serines are adjacent to the pxxp motif (ptppkrs637s638sfr) that binds the sh3 domain of abi. phosphorylation of c-abl by pak2 inhibits the interaction between the sh3 domain of abi2 and the pxxp motif of c-abl.	SIGNOR-160215
P08754	P20309	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-256882
O00443	P08069	0	phosphorylation	up-regulates	0.275	Analysis of the ability of the full-length igfr and its mutant receptors described above to associate with phosphatidylinositol 3 kinase indicated that the association required ptk activity and tyrosine [?] Phosphorylation of the receptors and correlated well with their transforming activities	SIGNOR-32076
P10275	P01148	2	binding	down-regulates activity	0.459	GnRH antagonizes testosterone activation of the human androgen receptor in SCL60 cells. Gonadotropin-Releasing Hormone Functionally Antagonizes Testosterone Activation of the Human Androgen Receptor in Prostate Cells through Focal Adhesion Complexes Involving Hic-5	SIGNOR-259267
P56704	O75197	2	binding	up-regulates activity	0.699	Ligands such as wnt1, wnt3a, and wnt8 couple the seventransmembrane domain receptor frizzled (fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (lrp5/6) to activate wnt?Beta-catenin signaling.All the frizzled genes studied have	SIGNOR-169657
Q13426	O14647	0	relocalization	up-regulates quantity	0.2	CHD2 Promotes the Recruitment of Core NHEJ Factors. overexpression of ATPase-dead CHD2 (K515R; Figure S5F), but not wild-type CHD2, also reduced the recruitment of XRCC4 (Figure 5E). Together, these findings suggest that the chromatin remodeling activity of CHD2 promotes the efficient assembly of NHEJ complexes at DSBs.	SIGNOR-264528
Q00987	Q92831	1	ubiquitination	down-regulates quantity by destabilization	0.621	Consistently, overexpression of MDM2 in p53 null cells caused the reduction of the protein level of PCAF, but not the mRNA level.\|MDM2 ubiquitinated PCAF in vitro and in cells.	SIGNOR-278825
P17252	Q13131	1	phosphorylation	down-regulates activity	0.2	Purified PKC and Akt both phosphorylated AMPKα1 Ser487 in vitro with similar efficiency. PKC activation was associated with reduced AMPK activity, as inhibition of PKC increased AMPK activity and phorbol esters inhibited AMPK, an effect lost in cells expressing mutant AMPKα1 Ser487Ala. Consistent with a pathophysiological role for this modification, AMPKα1 Ser487 phosphorylation was inversely correlated with insulin sensitivity in human muscle.	SIGNOR-276459
Q12933	P36941	2	binding	up-regulates activity	0.586	Endogenous association of traf2, traf3, ciap1, and smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis.	SIGNOR-97950
Q15025	Q9UHD2	0	phosphorylation	down-regulates quantity by destabilization	0.375	TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1	SIGNOR-275733
P51608	P67809	2	binding	up-regulates activity	0.506	In this study, we show that MeCP2 interacts with the RNA-binding protein Y box-binding protein 1 and regulates splicing of reporter minigenes. Importantly, we found aberrant alternative splicing patterns in a mouse model of RTT. Thus, we uncovered a previously uncharacterized function of MeCP2 that involves regulation of splicing, in addition to its role as a transcriptional repressor.	SIGNOR-277700
Q16566	P29475	1	phosphorylation	down-regulates activity	0.357	It was found that purified recombinant nNOS was phosphorylated by CaM-K Ialpha, CaM-K IIalpha, and CaM-K IV at Ser847 in vitro. Replacement of Ser847 with Ala (S847A) prevented phosphorylation by CaM kinases. Phosphorylated recombinant wild-type nNOS at Ser847 (approximately 0.5 mol of phosphate incorporation into nNOS) exhibited a 30% decrease of Vmax with little change of both the Km for L-arginine and Kact for CaM relative to unphosphorylated enzyme. The activity of mutant S847D was decreased to a level 50-60% as much as the wild-type enzyme. The decreased NOS enzyme activity of phosphorylated nNOS at Ser847 and mutant S847D was partially due to suppression of CaM binding, but not to impairment of dimer formation which is thought to be essential for enzyme activation.	SIGNOR-250713
Q9UGL1	Q16695	1	demethylation	up-regulates activity	0.2	KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.	SIGNOR-264303
Q9Y4X5	Q9NZQ7	1	polyubiquitination	down-regulates quantity by destabilization	0.2	We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation.	SIGNOR-277553
P17600	P60709	2	binding	up-regulates activity	0.299	Synapsins, a family of neuron-specific phosphoproteins, have been demonstrated to regulate the availability of synaptic vesicles for exocytosis by binding to both synaptic vesicles and the actin cytoskeleton in a phosphorylation-dependent manner.	SIGNOR-269184
P68400	O75676	1	phosphorylation	up-regulates activity	0.281	Here we report that the CK2 protein kinase, which contributes to NF-kappaB activation following UV radiation in a p38-dependent manner, physically interacts with MSK2 but not MSK1 and that CK2 inhibition specifically impairs UV-induced MSK2 kinase activation. A putative site of CK2 phosphorylation was mapped to MSK2 residue Ser(324) and when substituted to alanine (S324A) also compromised MSK2 activity.Serine 324 is required for UV-induced MSK2 activation and for autophosphorylation at MSK2-Ser196.	SIGNOR-276268
P19419	P45984	0	phosphorylation	up-regulates activity	0.49	However, both of these stimuli strongly activate two other mapks, jnk1 and jnk2, and stimulate elk-1 transcriptional activity and phosphorylation jnk phosphorylation sites include ser383 and ser389, the major residues whose phosphorylation is responsible for enhancement of elk-1 trascriptional activity.	SIGNOR-247062
P41143	P08754	2	binding	up-regulates activity	0.461	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-256826
Q99677	P63096	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-257057
Q8IYT8	P54646	1	phosphorylation	down-regulates	0.304	We could prove that ulk1-mediated phosphorylation of ampk reduced its level of phosphorylation at t172 of the _-subunit and hence interferes with its catalytic activity. I	SIGNOR-173089
Q15418	Q8TB45	1	phosphorylation	down-regulates	0.492	We found that deptor was rapidly phosphorylated on three serines in a conserved degron, facilitating binding and ubiquitylation by the f box protein _trcp, with consequent proteasomal degradation of deptor. Phosphorylation of the _trcp degron in deptor is executed by ck1	SIGNOR-176883
Q13698	P68400	0	phosphorylation	up-regulates activity	0.2	To identify the regulatory sites of phosphorylation under physiologically relevant conditions, Ca(V)1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac Ca(V)1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that Ca(V)1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas Ca(V)1.1-T1579 is a substrate for casein kinase 2.	SIGNOR-263114
P49137	P15923	1	phosphorylation	up-regulates	0.52	Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2	SIGNOR-166643
P55957	P45984	0	phosphorylation	up-regulates activity	0.406	(c) The phosphorylation of recombinant Bid by JNK2 (in vitro kinase assay) prevents its cleavage by caspase-8	SIGNOR-279220
P09630	P04271	1	transcriptional regulation	up-regulates quantity by expression	0.2	HOXC6 and HOXC11 increase transcription of S100beta gene in BrdU-induced in vitro differentiation of GOTO neuroblastoma cells into Schwannian cells.	SIGNOR-261646
P25116	P09471	2	binding	up-regulates activity	0.424	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-257011
Q92934	Q08209	0	dephosphorylation	up-regulates activity	0.471	Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD\|Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis.	SIGNOR-248694
P01116	Q13671	2	binding	up-regulates	0.598	We demonstrate that the ras effector protein rin1 binds to activated ras with an affinity (k(d), 22 nm) similar to that observed for raf1.	SIGNOR-113970
Q5JU85	P42261	1	relocalization	up-regulates quantity	0.2	BRAG1 increases the synaptic recycling pool of AMPARs.these data suggest that the BRAG1 enhancement of AMPAR transmission is mediated by the increased expression of the recycling pool of synaptic GluA2/3 receptors.	SIGNOR-264912
Q9UQF2	Q12852	2	binding	down-regulates	0.516	Jip inhibits dlk dimerization.	SIGNOR-109046
P06241	Q05397	1	phosphorylation	up-regulates activity	0.602	Because Fyn deletion prevented FAK phosphorylation at tyrosine residues 397 and 576 (XREF_FIG), we generated a phosphorylation mimicking mutant of FAK to test whether restoring FAK phosphorylation in the fyn -/- mouse lung could restore lung vascular permeability responses to PAR1 agonist to the level seen in WT mice.\|Our findings that interaction of activated FAK with p120-catenins subsequent to Fyn activation of FAK facilitates reannealing of AJ leading to reestablishment of the basal endothelial barrier suggest that the Fyn-FAK pathway plays a critical role in restoring endothelial barrier function.	SIGNOR-278441
P48058	Q9BYB0	2	binding	up-regulates quantity	0.2	SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).	SIGNOR-264604
O75385	Q8TDY2	1	phosphorylation	up-regulates	0.913	Ulk1 and ulk2 are the kinase phosphorylating their binding proteins atg13 and fip200. Atg13 directly binds fip200 and mediates the interaction between fip200 and ulks.	SIGNOR-186992
P40337	P48200	1	ubiquitination	down-regulates quantity by destabilization	0.359	We show here that IRP2 can interact with pVHL in co-transfection/co-immunoprecipitation assays. Furthermore, pVHL is able to promote the ubiquitination and the decay of transfected IRP2.	SIGNOR-271421
P0DPK5	Q92831	0	acetylation	down-regulates activity	0.2	The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.	SIGNOR-269615
Q14103	P17612	0	phosphorylation	up-regulates	0.349	Protein kinase a enhances, whereas glycogen synthase kinase-3 beta inhibits, the activity of the exon 2-encoded transactivator domain of heterogeneous nuclear ribonucleoprotein d in a hierarchical fashion.	SIGNOR-116144
Q9H9S0	Q9UGL1	0	transcriptional regulation	down-regulates quantity by repression	0.308	Phosphorylation of KDM5B at Ser1456 attenuated the occupancy of KDM5B on the promoters of pluripotency genes.	SIGNOR-273451

P17096

P06493

0

phosphorylation

down-regulates

0.384

Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation.

SIGNOR-158604

Q08334

Q8IZI9

2

binding

up-regulates

0.848

Il-28 and il-29 interacted with a heterodimeric class ii cytokine receptor that consisted of il-10 receptor beta (il-10rbeta) and an orphan class ii receptor chain, designated il-28ralpha.

SIGNOR-96246

Q5VT25

P60953

2

binding

up-regulates activity

0.792

Myotonic dystrophy kinase-related Cdc42-binding kinase acts as a Cdc42 effector in promoting cytoskeletal reorganization|MRCK alpha and Cdc42V12 colocalize, particularly at the cell periphery in transfected HeLa cells. Microinjection of plasmid encoding MRCK alpha resulted in actin and myosin reorganization.

SIGNOR-262593

Q92997

Q8IZQ1

0

relocalization

down-regulates quantity by destabilization

0.251

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

SIGNOR-266793

O94813

Q8NFU7

0

transcriptional regulation

up-regulates quantity by expression

0.2

Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9.

SIGNOR-259093

O43186

Q96SL8

2

binding

down-regulates activity

0.455

Interaction of Fiz1 and NRL-leucine zipper was validated by GST pulldown assays and co-immunoprecipitation from bovine retinal nuclear extracts. Fiz1 suppressed NRL- but not CRX-mediated transactivation of rhodopsin promoter activity in transiently transfected CV1 cells.

SIGNOR-223799

P52566

Q9NYL2

0

phosphorylation

down-regulates activity

0.2

In the present study, we provide evidence that ZAK serves as a RhoGDIbeta kinase, and demonstrate the phosphorylation of RhoGDIbeta by ZAK in vitro, as well as the physical association between ZAK and RhoGDIbeta.|These two proteins could negatively regulate one another such that ZAK suppresses RhoGDIbeta functions through phosphorylation and RhoGDIbeta counteracts the effects of ZAK by physical interaction.

SIGNOR-279633

Q04760

P21802

0

phosphorylation

up-regulates activity

0.2

We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).

SIGNOR-276184

P17542

P62256

1

transcriptional regulation

up-regulates quantity by expression

0.326

Tal1 expression activated UBE2H expression, whereas Tal1 knock-down reduced UBE2H expression and ubiquitin transfer activity.|Binding of Tal1 to UBE2H was confirmed by chromatin immunoprecipitation.

SIGNOR-269000

Q04760

P22607

0

phosphorylation

up-regulates activity

0.2

We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).

SIGNOR-276181

O15198

Q13485

1

phosphorylation

up-regulates

0.685

Whereas alk5 signalling is mediated by phosphorylation of smad2 and smad3 proteins, alk1 signalling is mediated by smad1, smad5, and smad8. Activated smads form a complex with the common smad (co-smad; smad4 in mammals) and shuttle into the nucleus.

SIGNOR-168740

Q96J92

O95747

1

phosphorylation

up-regulates activity

0.48

In addition, WNK4 phosphorylates and activates Ste20-type kinases SPAK and OSR1, which in turn phosphorylate and activate NCC [ xref ; xref ].|Later studies also indicate that WNK4 phosphorylates and activates Ste20-type kinases SPAK and OSR1, which in turn phosphorylates and activates NCC ; ].

SIGNOR-278389

Q16549

P28324

1

phosphorylation

up-regulates

0.2

In contrast, the tcf sap-1a is efficiently phosphorylated by p38 map kinase in vitro and in vivo on the homologous residues ser381 and ser387

SIGNOR-47771

P11308

O15550

0

transcriptional regulation

down-regulates quantity by repression

0.2

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

SIGNOR-260033

P68400

P03372

1

phosphorylation

down-regulates

0.246

Additionally protein kinase ck2 was identified as a kinase that phosphorylated eralpha at s282 and s559 s282 and s559 represent the second and third sites of er_ regulation by ck2. Remarkably, mutation of s282 or s559 to alanine resulted in near opposite functional effects on er_ as compared to mutation of s167 to alanine. Er_ ligand independent transcriptional activity was markedly enhanced upon mutation of s282 and s559 to alanine

SIGNOR-162653

P35372

P02775

0

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

Q08209

Q12968

1

dephosphorylation

up-regulates

0.538

Calcineurin directly dephosphorylates nfat resulting in the nuclear import of nfat.

SIGNOR-176376

P54252

O95155

0

polyubiquitination

down-regulates quantity by destabilization

0.578

Mammalian E4B (UFD2a), a ubiquitin chain assembly factor (E4), copurified with the polyubiquitylation activity for ataxin-3. E4B interacted with, and thereby mediated polyubiquitylation of, ataxin-3. Collectively, these data suggest that E4B promotes the degradation of ataxin-3, and that this effect surmounts the stabilization of ataxin-3 conferred by expansion of the polyglutamine tract.

SIGNOR-271502

P49683

P08754

2

binding

up-regulates activity

0.278

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-256837

P01019-PRO_0000032458

P50052

2

binding

up-regulates activity

0.2

Ang II initiates most of the RAS-attributed physiologic effects through selective interactions with G-proteincoupled Ang II type 1 (AT1) or type 2 (AT2) receptors and subsequent activation of distinct intra cellular signaling pathways

SIGNOR-260237

Q9H0K1

Q53ET0

1

phosphorylation

down-regulates

0.743

Phosphorylation on the ser171 residue of crtc2 by ampk and ampk-related kinases, including the salt-inducible kinases (siks), is critical for determining the activity, cellular localization, and degradation of crtc2

SIGNOR-142218

Q05655

Q16658

1

phosphorylation

down-regulates activity

0.324

Phosphorylation of human fascin inhibits its actin binding and bundling activities.

SIGNOR-248944

Q12772

Q8WU17

0

ubiquitination

down-regulates quantity

0.477

Induction of TRC8 destabilized the precursor forms of the transcription factors SREBP-1 and SREBP-2. TRC8 destablizes SREBP precursors in a RING and proteasome-dependent manner

SIGNOR-271958

Q13253

Q13873

2

binding

down-regulates activity

0.588

Noggin binds the domain that is re-quired for bmp-7 to interact with bmp type i and type ii receptors.Noggin Inhibits bmp by blocking the molecular interfaces of the binding epitopes for both type i and type ii receptors (pmid 12478285)

SIGNOR-195612

Q16828

Q13164

1

dephosphorylation

down-regulates activity

0.646

However, whilst the interaction itself might be difficult to monitor, DUSP6 should still be able to promote the de-phosphorylation of ERK5 in cells if it is an ERK5 phosphatase.To test this HEK293 cells were transiently transfected with HA-ERK2 or HA-ERK5 together with EGFP-MEK1E (a constitutively active version of MEK1) or EGFP-MEK5D (a constitutively active version of MEK5).|Whilst one can envisage scenarios in which the interaction between DUSPs and their substrates might be transient, DUSP6 should still be able to promote the de-phosphorylation and inactivation of ERK5.

SIGNOR-277007

Q92973

O15534

1

relocalization

up-regulates activity

0.268

The non-classical nuclear import carrier Transportin 1 modulates circadian rhythms through its effect on PER1 nuclear localization

SIGNOR-262102

Q16204

P27361

0

phosphorylation

up-regulates activity

0.367

We have characterized the H4(D10S170) gene product, showing that it is a ubiquitously expressed 55 KDa nuclear and cytosolic protein that is phosphorylated following serum stimulation. This phosphorylation was found to depend on mitogen-activated protein kinase (MAPK) Erk1/2 activity and to be associated to the relocation of H4(D10S170) from the nucleus to the cytosol. S244 is the major target residue of ERK1

SIGNOR-276003

O75444

P14921

2

binding

down-regulates

0.425

Full-length c-maf binds to the c-myb and ets-1. / c-maf inhibits c-myb and ets-1 transcriptional activity.

SIGNOR-56808

Q9NUX5

O14746

2

binding

up-regulates

0.673

We find that tpp1 and pot1 form a complex with telomeric dna that increases the activity and processivity of the human telomerase core enzyme.

SIGNOR-152327

O75962

P43146

2

binding

up-regulates quantity

0.606

TrioY2622 is required for both netrin-1-induced activation of Rac1 and enhanced association with DCC. Phosphorylation of Trio at Tyr2622 participates in maintaining the level of surface DCC at the growth cone plasma membrane leading to axon outgrowth. Therefore, we propose that TrioY2622 is essential for the proper assembly and stability of the DCC/Trio signaling complex at the cell surface of growth cones in order to mediate netrin-1-induced cortical axon outgrowth.

SIGNOR-273856

P43115

P00533

1

relocalization

up-regulates quantity

0.332

These results demonstrate that PGE2 -mediated EGFR nuclear translocation requires the EP3 receptor.

SIGNOR-278884

P50148

P50406

2

binding

up-regulates activity

0.344

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-257340

P19086

P30542

2

binding

up-regulates activity

0.335

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-257092

P62140

Q00987

1

dephosphorylation

up-regulates quantity by stabilization

0.2

Three phosphorylation sites identified are Ser342, Ser367, and Ser403. In the present study, we identify protein phosphatase 1 (PP1) as a negative regulator in the p53 signaling pathway. PP1 directly interacts with Mdmx and specifically dephosphorylates Mdmx at Ser367. The dephosphorylation of Mdmx increases its stability and thereby inhibits p53 activity.

SIGNOR-248577

Q9UL54

P52564

2

binding

up-regulates activity

0.649

Cotransfection experiments suggested that tao2 selectively activates mek3 and mek6 but not meks 1, 4, or 7.

SIGNOR-70950

P38936

P14635

2

binding

down-regulates

0.829

P21-mediated degradation of cyclin b1 in response to dna damage is necessary for the maintenance of g2 cell cycle arrest.

SIGNOR-183498

Q86XR7

Q02156

0

phosphorylation

up-regulates

0.573

Here we show that tram is transiently phosphorylated by pkcepsilon on serine-16 our study provides a possible target for these molecules in lps signaling. Dag may activate pkc?, Leading to the phosphorylation and activation of tram.

SIGNOR-146991

P04150

Q9Y616

1

transcriptional regulation

up-regulates quantity

0.36

We show that glucocorticoids and non-typeable Haemophilus influenzae synergistically upregulate IRAK-M expression via mutually and synergistically enhancing p65 and glucocorticoid receptor binding to the IRAK-M promoter

SIGNOR-259287

Q9GZY8

Q13131

0

phosphorylation

up-regulates activity

0.2

A screen for substrates of AMPK identified mitochondrial fission factor (MFF), a mitochondrial outer-membrane receptor for DRP1, the cytoplasmic guanosine triphosphatase that catalyzes mitochondrial fission.

SIGNOR-245953

P45984

P31947

1

phosphorylation

down-regulates

0.2

Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-189

SIGNOR-124027

P49841

Q13418

0

phosphorylation

down-regulates activity

0.69

ILK can also directly phosphorylates GSK-3\u03b2 at Ser 9, inactivate it, and lead to activation of some transcription factors [ ].|ILK knockdown activates GSK-3beta.

SIGNOR-278252

O95071

Q92547

1

polyubiquitination

down-regulates quantity by destabilization

0.462

Using an in vitro reconstitution, specific E2 (ubiquitin-conjugating) enzymes (human UbcH4, UbcH5B, and UbcH5C) transferred ubiquitin molecules to hHYD, leading to the ubiquitination of TopBP1. TopBP1 was usually ubiquitinated and degraded by the proteosome, whereas X-irradiation diminished the ubiquitination of TopBP1 probably via the phosphorylation, resulting in the stable colocalization of up-regulated TopBP1 with gamma-H2AX nuclear foci in DNA breaks.

SIGNOR-272667

Q9NYL2

P52566

1

phosphorylation

down-regulates activity

0.2

In the present study, we provide evidence that ZAK serves as a RhoGDIbeta kinase, and demonstrate the phosphorylation of RhoGDIbeta by ZAK in vitro, as well as the physical association between ZAK and RhoGDIbeta.|These two proteins could negatively regulate one another such that ZAK suppresses RhoGDIbeta functions through phosphorylation and RhoGDIbeta counteracts the effects of ZAK by physical interaction.

SIGNOR-279633

Q9UKB1

P63208

2

binding

up-regulates

0.801

The scf is composed of skp1, cdc53/cul1, and a specificity-conferring f-box protein. F-box proteins contain two domains, an f-box motif that binds skp1 and allows assembly into skp1/cdc53 complexes, and a second proteinprotein interaction domain that interacts specifically with one or more target proteins. Cdc53/cul1, in turn, interacts with both the e2 and the skp1/f-box protein complex.

SIGNOR-64505

P23470

O60674

1

dephosphorylation

down-regulates activity

0.287

Deeper examination shows that JAKs are critically involved in integrin-mediated monocyte adhesion and that PTPRG activation leads to JAK2 dephosphorylation on the critical 1007–1008 phosphotyrosine residues, implying JAK2 inhibition and thus explaining the antiadhesive role of PTPRG.

SIGNOR-254690

P31751

P30405

1

phosphorylation

up-regulates activity

0.2

In turn, mitochondrial Akt2 phosphorylates Ser31 in cyclophilin D (CypD), a regulator of organelle functions. Akt2-phosphorylated CypD supports mitochondrial bioenergetics and opposes tumor cell death, conferring resistance to PI3K therapy.

SIGNOR-276875

P56693

P49841

0

phosphorylation

down-regulates quantity

0.406

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

SIGNOR-279617

Q13017

Q13882

0

phosphorylation

up-regulates

0.2

Breast tumor kinase phosphorylates p190rhogap to regulate rho and ras and promote breast carcinoma growth, migration, and invasion. Brk phosphorylates p190 at the y(1105) residue both in vitro and in vivo, thereby promoting the association of p190 with p120rasgap (p120). As a consequence, brk stimulates p190 and attenuates p120 functions, leading to rhoa inactivation and ras activation, respectively.

SIGNOR-181452

Q13485

O43541

2

binding

down-regulates activity

0.574

On the other hand, Smad6 competes with R-Smad and forms a non-functional complex with Smad4, which will inhibit BMP signaling in bone formation. Smad6 is involved in a negative feedback loop regulating BMP signaling and is required to limit BMP signaling during endochondral bone formation.

SIGNOR-195648

P08174

P48960

2

binding

up-regulates

0.2

This interaction may facilitate cell activation and migration through the blood-brain barrier. In addition, cd97-cd55 interactions in the parenchyma of the brain may contribute to the inflammation.

SIGNOR-95458

Q86VZ6

P49116

2

binding

down-regulates

0.453

Tip27 interacts specifically with tak1 / tip27 functions as a tak1-selective repressor

SIGNOR-127900

P15923

P15172

2

binding

up-regulates activity

0.806

In addition we demonstrate that myod, in conjunction with e12/e47-like proteins, is functioning as a regulatory nodal point for activation of several other downstream muscle regulators.

SIGNOR-20540

P48729

P12830

1

phosphorylation

down-regulates activity

0.312

Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts|CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846

SIGNOR-274045

Q9BUB5

O00141

0

phosphorylation

down-regulates activity

0.2

We show that SGK1 phosphorylates MNK1 at a conserved site, which represses its activity.

SIGNOR-277357

P13500

O75626

0

transcriptional regulation

down-regulates quantity by repression

0.2

Blimp-1 binds to the proinflammatory cytokine/chemokine genes, Il-6 and Ccl2, and negatively regulates their expression.

SIGNOR-271679

P15172

Q13547

2

binding

down-regulates

0.547

Interaction of myod with hdac1 in undifferentiated myoblasts mediates repression of muscle-specific gene expression.

SIGNOR-111243

P45984

Q12968

1

relocalization

down-regulates

0.711

Jnks directly phosphorylate nuclear factor of activated t-cell (nfat) transcription factors, thus antagonizing the effects of calcium-regulated signaling through the protein phosphatase calcineurin.

SIGNOR-103360

P10636-2

Q02156

0

phosphorylation

down-regulates activity

0.271

We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.

SIGNOR-275444

P21731

O95837

2

binding

up-regulates activity

0.47

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-257023

P12830

P56545

0

transcriptional regulation

down-regulates quantity by repression

0.381

Overexpression of the CtBP2 protein enhanced the repression activity of the E-cadherin promoter in a dose-dependent manner, whereas overexpression of ataxin-1 increased the activity of the E-cadherin promoter in a dose-dependent manner

SIGNOR-261578

P41146

P08754

2

binding

up-regulates activity

0.458

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-256865

O60928

P17612

0

phosphorylation

up-regulates

0.2

Pka activation induced an increase of kir7.1 currents. This effect was absent in mutant kir7.1 channels lacking pka consensus site (287)s

SIGNOR-181859

P55085

P50148

2

binding

up-regulates activity

0.406

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

SIGNOR-257300

Q13177

P00519

1

phosphorylation

down-regulates

0.415

The interaction of c-abl with the abl interactor protein abi2 is shown to be negatively regulated by phosphorylation of serines 637 and 638. These serines are adjacent to the pxxp motif (ptppkrs637s638sfr) that binds the sh3 domain of abi. phosphorylation of c-abl by pak2 inhibits the interaction between the sh3 domain of abi2 and the pxxp motif of c-abl.

SIGNOR-160215

P08754

P20309

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-256882

O00443

P08069

0

phosphorylation

up-regulates

0.275

Analysis of the ability of the full-length igfr and its mutant receptors described above to associate with phosphatidylinositol 3 kinase indicated that the association required ptk activity and tyrosine [?] Phosphorylation of the receptors and correlated well with their transforming activities

SIGNOR-32076

P10275

P01148

2

binding

down-regulates activity

0.459

GnRH antagonizes testosterone activation of the human androgen receptor in SCL60 cells. Gonadotropin-Releasing Hormone Functionally Antagonizes Testosterone Activation of the Human Androgen Receptor in Prostate Cells through Focal Adhesion Complexes Involving Hic-5

SIGNOR-259267

P56704

O75197

2

binding

up-regulates activity

0.699

Ligands such as wnt1, wnt3a, and wnt8 couple the seventransmembrane domain receptor frizzled (fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (lrp5/6) to activate wnt?Beta-catenin signaling.All the frizzled genes studied have

SIGNOR-169657

Q13426

O14647

0

relocalization

up-regulates quantity

0.2

CHD2 Promotes the Recruitment of Core NHEJ Factors. overexpression of ATPase-dead CHD2 (K515R; Figure S5F), but not wild-type CHD2, also reduced the recruitment of XRCC4 (Figure 5E). Together, these findings suggest that the chromatin remodeling activity of CHD2 promotes the efficient assembly of NHEJ complexes at DSBs.

SIGNOR-264528

Q00987

Q92831

1

ubiquitination

down-regulates quantity by destabilization

0.621

Consistently, overexpression of MDM2 in p53 null cells caused the reduction of the protein level of PCAF, but not the mRNA level.|MDM2 ubiquitinated PCAF in vitro and in cells.

SIGNOR-278825

P17252

Q13131

1

phosphorylation

down-regulates activity

0.2

Purified PKC and Akt both phosphorylated AMPKα1 Ser487 in vitro with similar efficiency. PKC activation was associated with reduced AMPK activity, as inhibition of PKC increased AMPK activity and phorbol esters inhibited AMPK, an effect lost in cells expressing mutant AMPKα1 Ser487Ala. Consistent with a pathophysiological role for this modification, AMPKα1 Ser487 phosphorylation was inversely correlated with insulin sensitivity in human muscle.

SIGNOR-276459

Q12933

P36941

2

binding

up-regulates activity

0.586

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

SIGNOR-97950

Q15025

Q9UHD2

0

phosphorylation

down-regulates quantity by destabilization

0.375

TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1

SIGNOR-275733

P51608

P67809

2

binding

up-regulates activity

0.506

In this study, we show that MeCP2 interacts with the RNA-binding protein Y box-binding protein 1 and regulates splicing of reporter minigenes. Importantly, we found aberrant alternative splicing patterns in a mouse model of RTT. Thus, we uncovered a previously uncharacterized function of MeCP2 that involves regulation of splicing, in addition to its role as a transcriptional repressor.

SIGNOR-277700

Q16566

P29475

1

phosphorylation

down-regulates activity

0.357

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

SIGNOR-250713

Q9UGL1

Q16695

1

demethylation

up-regulates activity

0.2

KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.

SIGNOR-264303

Q9Y4X5

Q9NZQ7

1

polyubiquitination

down-regulates quantity by destabilization

0.2

We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation.

SIGNOR-277553

P17600

P60709

2

binding

up-regulates activity

0.299

Synapsins, a family of neuron-specific phosphoproteins, have been demonstrated to regulate the availability of synaptic vesicles for exocytosis by binding to both synaptic vesicles and the actin cytoskeleton in a phosphorylation-dependent manner.

SIGNOR-269184

P68400

O75676

1

phosphorylation

up-regulates activity

0.281

Here we report that the CK2 protein kinase, which contributes to NF-kappaB activation following UV radiation in a p38-dependent manner, physically interacts with MSK2 but not MSK1 and that CK2 inhibition specifically impairs UV-induced MSK2 kinase activation. A putative site of CK2 phosphorylation was mapped to MSK2 residue Ser(324) and when substituted to alanine (S324A) also compromised MSK2 activity.Serine 324 is required for UV-induced MSK2 activation and for autophosphorylation at MSK2-Ser196.

SIGNOR-276268

P19419

P45984

0

phosphorylation

up-regulates activity

0.49

However, both of these stimuli strongly activate two other mapks, jnk1 and jnk2, and stimulate elk-1 transcriptional activity and phosphorylation jnk phosphorylation sites include ser383 and ser389, the major residues whose phosphorylation is responsible for enhancement of elk-1 trascriptional activity.

SIGNOR-247062

P41143

P08754

2

binding

up-regulates activity

0.461

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-256826

Q99677

P63096

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-257057

Q8IYT8

P54646

1

phosphorylation

down-regulates

0.304

We could prove that ulk1-mediated phosphorylation of ampk reduced its level of phosphorylation at t172 of the _-subunit and hence interferes with its catalytic activity. I

SIGNOR-173089

Q15418

Q8TB45

1

phosphorylation

down-regulates

0.492

We found that deptor was rapidly phosphorylated on three serines in a conserved degron, facilitating binding and ubiquitylation by the f box protein _trcp, with consequent proteasomal degradation of deptor. Phosphorylation of the _trcp degron in deptor is executed by ck1

SIGNOR-176883

Q13698

P68400

0

phosphorylation

up-regulates activity

0.2

To identify the regulatory sites of phosphorylation under physiologically relevant conditions, Ca(V)1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac Ca(V)1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that Ca(V)1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas Ca(V)1.1-T1579 is a substrate for casein kinase 2.

SIGNOR-263114

P49137

P15923

1

phosphorylation

up-regulates

0.52

Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2

SIGNOR-166643

P55957

P45984

0

phosphorylation

up-regulates activity

0.406

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

SIGNOR-279220

P09630

P04271

1

transcriptional regulation

up-regulates quantity by expression

0.2

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

SIGNOR-261646

P25116

P09471

2

binding

up-regulates activity

0.424

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-257011

Q92934

Q08209

0

dephosphorylation

up-regulates activity

0.471

Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD|Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis.

SIGNOR-248694

P01116

Q13671

2

binding

up-regulates

0.598

We demonstrate that the ras effector protein rin1 binds to activated ras with an affinity (k(d), 22 nm) similar to that observed for raf1.

SIGNOR-113970

Q5JU85

P42261

1

relocalization

up-regulates quantity

0.2

BRAG1 increases the synaptic recycling pool of AMPARs.these data suggest that the BRAG1 enhancement of AMPAR transmission is mediated by the increased expression of the recycling pool of synaptic GluA2/3 receptors.

SIGNOR-264912

Q9UQF2

Q12852

2

binding

down-regulates

0.516

Jip inhibits dlk dimerization.

SIGNOR-109046

P06241

Q05397

1

phosphorylation

up-regulates activity

0.602

Because Fyn deletion prevented FAK phosphorylation at tyrosine residues 397 and 576 (XREF_FIG), we generated a phosphorylation mimicking mutant of FAK to test whether restoring FAK phosphorylation in the fyn -/- mouse lung could restore lung vascular permeability responses to PAR1 agonist to the level seen in WT mice.|Our findings that interaction of activated FAK with p120-catenins subsequent to Fyn activation of FAK facilitates reannealing of AJ leading to reestablishment of the basal endothelial barrier suggest that the Fyn-FAK pathway plays a critical role in restoring endothelial barrier function.

SIGNOR-278441

P48058

Q9BYB0

2

binding

up-regulates quantity

0.2

SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).

SIGNOR-264604

O75385

Q8TDY2

1

phosphorylation

up-regulates

0.913

Ulk1 and ulk2 are the kinase phosphorylating their binding proteins atg13 and fip200. Atg13 directly binds fip200 and mediates the interaction between fip200 and ulks.

SIGNOR-186992

P40337

P48200

1

ubiquitination

down-regulates quantity by destabilization

0.359

We show here that IRP2 can interact with pVHL in co-transfection/co-immunoprecipitation assays. Furthermore, pVHL is able to promote the ubiquitination and the decay of transfected IRP2.

SIGNOR-271421

P0DPK5

Q92831

0

acetylation

down-regulates activity

0.2

The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.

SIGNOR-269615

Q14103

P17612

0

phosphorylation

up-regulates

0.349

Protein kinase a enhances, whereas glycogen synthase kinase-3 beta inhibits, the activity of the exon 2-encoded transactivator domain of heterogeneous nuclear ribonucleoprotein d in a hierarchical fashion.

SIGNOR-116144

Q9H9S0

Q9UGL1

0

transcriptional regulation

down-regulates quantity by repression

0.308

Phosphorylation of KDM5B at Ser1456 attenuated the occupancy of KDM5B on the promoters of pluripotency genes.

SIGNOR-273451