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
Q9UI08	Q13976	0	phosphorylation	down-regulates activity	0.2	Vertebrate Ena/VASP proteins are phosphorylated by PKA, as well as PKG, and the phosphorylation is required for full function in a number of cellular contexts	SIGNOR-268290
Q96GD4	Q9UKV0	1	phosphorylation	down-regulates	0.262	We define the precise site of aurb-mediated phosphorylation as a conserved serine within the nuclear localization signals of hdac4, hdac5, and hdac9 at ser265, ser278, and ser242, respectivelyduring mitosis, aurb-mediated phosphorylation may localize class iia hdacs to a phosphorylation gradient at the spindle midzone, permitting temporal and spatial regulatory mechanisms altering hdac protein interactions	SIGNOR-198654
Q12834	Q5XUX0	2	binding	down-regulates quantity by destabilization	0.398	Here we show that the low levels of FBXO31 are maintained through proteasomal degradation by anaphase-promoting complex/cyclosome (APC/C). We find that the APC/C coactivators CDH1 and CDC20 bind to a destruction-box (D-box) motif present in FBXO31 to promote its polyubiquitination and degradation in a cell-cycle-regulated manner, which requires phosphorylation of FBXO31 on serine-33 by the prosurvival kinase AKT.	SIGNOR-277378
Q9H4A3	Q9H2X9	1	phosphorylation	down-regulates activity	0.461	The activity of the neuronal specific KCC2 had recently been shown to be regulated by the WNK1 kinase, where phosphorylation decreased KCC2 activation .\|WNK1 phosphorylation of KCC2 occurs in immature neurons but is absent in adult neurons , , emphasizing a developmental role.	SIGNOR-280163
Q03060	P60568	1	transcriptional regulation	down-regulates quantity by repression	0.481	In this study we show that CREM is transcriptionally induced in T cells following stimulation through CD3 and CD28, binds to the IL-2 promoter in vivo, and suppresses IL-2 production.	SIGNOR-261576
O75116	Q15306	1	phosphorylation	up-regulates	0.417	Carock2 phosphorylated irf4 at either of 2 distinct phosphorylation sites, s446 and s447 / rock2-mediated phosphorylation of irf4 regulated the synthesis of il-17 and il-21 and the differentiation of th17 cells.	SIGNOR-167471
Q8IWU2	Q00535	0	phosphorylation	up-regulates	0.497	Here, we demonstrate that lmtk2 is phosphorylated on serine-1418 (lmtk2ser ) by cdk5/p35 and present evidence that this regulates its ability to phosphorylate pp1cthr __	SIGNOR-195329
P23458	P42226	1	phosphorylation	up-regulates activity	0.765	IL-4-stimulated Stat6 activation is mediated by Jak1 whereas Tyk2 is required for Stat6 activation in IL-13-treated monocytes	SIGNOR-249531
Q7LDG7	P28482	0	phosphorylation	down-regulates activity	0.396	ERK2 phosphorylates RasGRP2 at Ser394 located in the linker region implicated in its autoinhibition.	SIGNOR-279537
O75164	Q8NEZ5	0	ubiquitination	down-regulates quantity by destabilization	0.339	SCF(FBXO22) regulates histone H3 lysine 9 and 36 methylation levels by targeting histone demethylase KDM4A for ubiquitin-mediated proteasomal degradation	SIGNOR-273442
Q13164	Q15256	0	dephosphorylation	down-regulates activity	0.45	In this study we concentrated on whether and how PTP-SL, a kinase-interacting motif-containing PTP, might be involved in the down-regulation of the ERK5 signal\|Whereas inactivation of ERK5 by PTP-SL monitored in vitro is most probably simply due to the dephosphorylation of tyrosine 220 in the activating TEY motif	SIGNOR-248721
O43541	Q13485	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
Q969V1	P63092	2	binding	up-regulates activity	0.25	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -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 ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256795
P17302	P12931	0	phosphorylation	down-regulates	0.588	The oncogenic tyrosine kinase, v-src, phosphorylates connexin43 (cx43) on y247 and y265 and inhibits cx43 gap junctional communication (gjc), the process of intercellular exchange of ions and metabolites.	SIGNOR-148913
Q86UX7	P17252	0	phosphorylation	up-regulates activity	0.2	PKC-induced phosphorylation events, as we have shown kindlin-3 to be a PKC phosphorylation target (Fig. 6C), are often followed by rapid activation of phosphatases (38).	SIGNOR-266415
P06213	P54646	0	phosphorylation	up-regulates	0.372	Ampk phosphorylates and activates theinsulinreceptor, providing a direct link between ampk and theinsulin pathway.	SIGNOR-195324
P54764	P10912	1	phosphorylation	up-regulates activity	0.2	EphA4 binds to growth hormone receptor at both its extracellular and intracellular domains and phosphorylates growth hormone receptor when stimulated with a ligand.\|These findings suggest that EphA4 activates not only GHR, as shown above, but also JAK2 by direct phosphorylation.	SIGNOR-279461
Q9UN37	Q9Y3E7	1	cleavage	up-regulates activity	0.625	Here, we show, using high-speed atomic force microscopy and electron microscopy, that the AAA-type adenosine triphosphatase VPS4 constricts and cleaves ESCRT-III CHMP2A-CHMP3 helical filaments in vitro. Our results demonstrate that VPS4 actively constricts ESCRT-III filaments and cleaves them before their complete disassembly. We propose that the formation of ESCRT-III dome-like end caps by VPS4 within a membrane neck structure constricts the membrane to set the stage for membrane fission.	SIGNOR-260847
Q02962	Q04727	2	binding	down-regulates activity	0.456	In cell culture, Grg4 suppresses Pax2-mediated transcriptional activation and inhibits phosphorylation of the Pax2 activation domain by WNT signaling and JNK	SIGNOR-251710
P30679	P41968	2	binding	up-regulates activity	0.272	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-257358
Q15208	Q2M2I8	1	phosphorylation	up-regulates activity	0.27	We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation. AAK1 phosphorylation regulates dendrite branching and length	SIGNOR-263034
P42345	P31749	2	phosphorylation	up-regulates activity	0.929	The rictor-mtor complex directly phosphorylated akt/pkb on ser473 in vitro and facilitated thr308 phosphorylation by pdk1	SIGNOR-252599
Q16512	P29966	1	phosphorylation	down-regulates activity	0.365	PRK1 phosphorylates MARCKS at the PKC sites: serine 152, serine 156 and serine 163.	SIGNOR-249671
P17612	P35612	1	phosphorylation	down-regulates activity	0.283	Ser-726 and Ser-713 in the C-terminal MARCKS-related domains of - and -adducin, respectively, were identified as the major phosphorylation sites common for PKA and PKC. Phosphorylation by PKA, but not PKC, reduced the affinity of adducin for spectrin-F-actin complexes as well as the activity of adducin in promoting binding of spectrin to F-actin.	SIGNOR-250332
Q9HBW0	O95837	2	binding	up-regulates activity	0.484	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-257431
Q969H0	O96020	2	binding	down-regulates quantity by destabilization	0.436	Cdk2 (S384) and GSK3 (T380) prime cyclin E for destruction. The hyper-phosphorylated T380/S384 degron has high affinity for monomeric Fbw7α, which engages the remainder of the SCF to initiate cyclin E's ubiquitination by an E2 enzyme	SIGNOR-271642
P17812	P17252	0	phosphorylation	down-regulates	0.2	These data indicated that protein kinase c phosphorylation at ser(462) stimulates human ctp synthetase 1 activity, whereas phosphorylation at thr(455) inhibits activity.	SIGNOR-154621
Q9HB63	Q6ZN44	2	binding	up-regulates	0.61	The unc5hs are axon guidance receptors that mediate netrin-1-dependent chemorepulsion, and dependence receptors that mediate netrin-1-independent apoptosis.	SIGNOR-98483
P06241	P43146	1	phosphorylation	up-regulates activity	0.572	Fyn tyrosine kinase, but not Src, regulates the phosphorylation of DCC in N1E-115 neuroblastoma cells.Both DCC phosphorylation and Netrin-1-induced axon outgrowth are impaired in Fyn(-/-) CN and spinal cord explants. We propose that DCC is regulated by tyrosine phosphorylation and that Fyn is essential for the response of axons to Netrin-1. these results show that DCC is phosphorylated by Fyn, but not Src, in N1E-115 cells, and that tyrosines 1261 and 1418 are the major phosphorylation sites of Fyn in vivo.	SIGNOR-268176
O75581	O14640	2	binding	up-regulates activity	0.707	The Wnt–FZD–LRP5/6 trimeric complex recruits Dishevelled (DVL) and Axin through the intracellular domains of FZD and LRP5/6, resulting in inhibition of β-catenin phosphorylation and thus ensuing β-catenin stabilization.	SIGNOR-262526
O95835	P35240	2	binding	up-regulates	0.689	As expected, the nf2-/- fc-912 cells were defective in lats1/2 phosphorylation (figure s2e-f). Subcellular fractionation revealed a significant increase of endogenous lats1/2 in the cytoplasmic relative to the membrane fraction in the nf2-/- fc-912 schwann cells compared to the nf2+/+ fh-912 schwann cells (figure 2e). This localization defect was rescued by re-expression of nf2	SIGNOR-202604
P38405	Q5NUL3	2	binding	up-regulates activity	0.25	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256916
Q9UL54	P19419	1	phosphorylation	up-regulates activity	0.31	Transfection studies demonstrated that TAO2 stimulates phosphorylation of the TCF Elk1 on the major activating site, Ser383, and that TAO2 stimulates transactivation of Elk1 and the related TCF, Sap1.	SIGNOR-246638
Q9Y5H1	Q9Y5H9	2	binding	up-regulates activity	0.2	The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.	SIGNOR-265691
Q14145	Q13618	2	binding	up-regulates activity	0.95	Keap1 is a BTB-Kelch protein that functions as a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex. Keap1 targets its substrate, the Nrf2 transcription factor, for ubiquitination and subsequent degradation by the 26 S proteasome. The N-terminal BTB domain and central linker region of Keap1 bind Cul3, whereas the C-terminal Kelch domain of Keap1 binds Nrf2 via residues located within loops that extend out from the bottom of the Kelch domain	SIGNOR-268925
Q6Y7W6	Q92600	2	binding	up-regulates activity	0.2	Through interaction analysis of RQCD1 with full-length or partial proteins of GIGYF1 and GIGYF2, segments corresponding to 620-665th and 667-712th amino acids were identified as potential interacting regions on GIGYF1 and GIGYF2, respectively, with RQCD1. we found that RQCD1 was required for enhancement of the interaction of Grb10 with GIGYF1 and GIGYF2	SIGNOR-260058
Q8IUQ4	Q13535	0	phosphorylation	down-regulates activity	0.2	We have also demonstrated that DNA damage triggers disruption of the HIPK2-Siah-1 complex, resulting in HIPK2 stabilization and activation. Disruption of the HIPK2-Siah-1 complex is mediated by the ATM/ATR pathway and involves ATM/ATR-dependent phosphorylation of Siah-1 at Ser 19.	SIGNOR-276167
P23528	Q8WYL5	0	dephosphorylation	up-regulates activity	0.786	Differential activities, subcellular distribution and tissue expression patterns of three members of Slingshot family phosphatases that dephosphorylate cofilin.\|Cofilin, a key regulator of actin filament dynamics, is inactivated by phosphorylation at Ser-3 by LIM-kinases and is reactivated by dephosphorylation by a family of protein phosphatases, termed Slingshot (SSH).	SIGNOR-248762
Q99704	P06239	0	phosphorylation	up-regulates activity	0.6	Phosphorylation of p56 dok and p62 dok is increased following CD2 stimulation and requires Lck. Phosphorylation of Dok proteins by Lck might provide a mechanism by which SH2-containing proteins can be recruited and co-localized with their substrates.	SIGNOR-251373
Q15120	P08559	1	phosphorylation	down-regulates activity	0.871	Activity of the mammalian pyruvate dehydrogenase complex is regulated by phosphorylation-dephosphorylation of the alpha subunit of the pyruvate dehydrogenase (e1) component. Phosphorylation is carried out by four pyruvate dehydrogenase kinase (pdk) isoenzymes.	SIGNOR-109647
P51617	Q9HAT8	2	phosphorylation	up-regulates activity	0.781	The phosphorylation of Pellino2 by activated IRAK1 and IRAK4 could trigger and modulate the translocation of IRAKs from complex I to complex II.	SIGNOR-278947
P11511	Q13285	0	transcriptional regulation	up-regulates quantity by expression	0.479	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-271787
Q86YT6	P78504	1	ubiquitination	up-regulates activity	0.693	Mib1 is essential for the generation of functional notch ligands and regulates the classical notch ligands dll1, dll4, jag1, and jag2 in vertebrates mib1 is an essential e3 ubiquitin ligase for jag1 in the developing cerebellum.	SIGNOR-97388
P17612	P06241	2	phosphorylation	up-regulates	0.459	The serine 21 (s21) residue of fyn is a protein kinase a (pka) recognition site within an rxxs motif of the amino terminal sh4 domain of fyn. In addition, s21 is critical for fyn kinase-linked cellular signaling. Mutation of s21a blocks pka phosphorylation of fyn and alters its tyrosine kinase activity.	SIGNOR-167147
P28482	P07949	0	phosphorylation	up-regulates	0.423	We hypothesized that ret could directly phosphorylate fak and erk. erk 2 could be phosphorylated at y187 (y204 in erk1).	SIGNOR-140294
P24928	O00308	0	ubiquitination	down-regulates quantity	0.387	WWP2 ubiquitylates RNA polymerase II for DNA-PK-dependent transcription arrest and repair at DNA breaks\|In response to DSBs, WWP2 targets the RNAPII subunit RPB1 for K48-linked ubiquitylation, thereby driving DNA-PK- and proteasome-dependent eviction of RNAPII.	SIGNOR-268851
P41236	Q13315	0	phosphorylation	down-regulates	0.2	Atm phosphorylates i-2 on serine 43, leading to the dissociation of the pp1-i-2 complex and the activation of pp1.	SIGNOR-160648
O75144	P05771	0	phosphorylation	up-regulates activity	0.2	PKCα and PKCβ are required for phosphorylation of ICOSL and ICOSL-mediated cytokine induction	SIGNOR-273797
P10275	P06493	0	phosphorylation	up-regulates	0.53	At first, the data show that cdk5 enables phosphorylation of ar at ser-81 site through direct biochemical interaction and, therefore, results in the stabilization of ar proteins although ar was reported as substrates for cdk9 (5) as well as cdk1	SIGNOR-175692
Q9Y6N7	P00519	0	phosphorylation	down-regulates	0.606	Abl functions to antagonize robo signaling both abl and ena can directly bind to robo's cytoplasmic domain.	SIGNOR-78993
P53350	Q2M2Z5	1	phosphorylation	up-regulates	0.519	Here, we identify a novel centrosomal substrate of plk1, kizuna (kiz), depletion of which causes fragmentation and dissociation of the pericentriolar material from centrioles at prometaphase, resulting in multipolar spindles. Plk1 maintains the integrity of the spindle poles by phosphorylating kiz.	SIGNOR-149630
Q96SB4	Q9Y5S9	1	phosphorylation	down-regulates	0.261	We demonstrate that y14 is phosphorylated at its repeated arginine/serine (rs) dipeptides, likely by sr protein-specific kinases. Phosphorylation of y14 abolished its interaction with ejc components as well as factors that function downstream of the ejc.	SIGNOR-139555
P29803	Q15119	0	phosphorylation	down-regulates	0.548	Kinetic and regulatory properties of recombinant human pdh2 and pdh1 were compared in this study. Site-specific phosphorylation/dephosphorylation of the three phosphorylation sites by four pdh kinases (pdk1-4) and two pdh phosphatases (pdp1-2) were investigated by substituting serines with alanine or glutamate in pdhs.	SIGNOR-143970
P35638	P68400	0	phosphorylation	down-regulates activity	0.344	CHOP transcription factor phosphorylation by casein kinase 2 inhibits transcriptional activation. \| The serine to alanine substituted site CHOP mutant was not phosphorylated by CK2, indicating that serines 14–15 and 30–31 of CHOP are the CK2 phosphoacceptor sites	SIGNOR-250850
Q16637	Q93008	0	deubiquitination	up-regulates quantity by stabilization	0.28	Ubiquitin-specific Protease 9x Deubiquitinates and Stabilizes the Spinal Muscular Atrophy Protein-Survival Motor Neuron	SIGNOR-253113
Q15139	Q92481	1	phosphorylation	down-regulates activity	0.295	Mechanistically, we observed that PKD phosphorylates AP2\u03b2 at Ser-258 and Ser-277 and suppresses its nuclear accumulation.\|Using ChIP analyses, here we found that PKD knockdown in HUVECs increases binding of AP2beta to the VEGFR-2 promoter.	SIGNOR-279267
O14757	Q08050	1	phosphorylation	up-regulates activity	0.371	In addition, upon treatment with genotoxic agents, the checkpoint kinases Chk1 and Chk2 also phosphorylate and activate FOXM1.	SIGNOR-280224
O95379	P63096	2	binding	up-regulates activity	0.2	TNFAIP8: a new effector for Galpha(i) coupling to reduce cell death and induce cell transformation	SIGNOR-256491
Q15361	Q9GZV5	2	binding	up-regulates	0.313	Taz is a coactivator for pax8 and ttf-1, two transcription factors involved in thyroid differentiation. / we show that this interaction leads to a significant enhancement of the transcriptional activity of pax8 and ttf-1 on the thyroglobulin promoter thus suggesting a role of taz in the control of genes involved in thyroid development and differentiation.	SIGNOR-182296
Q96AX2	P17252	0	phosphorylation	down-regulates activity	0.2	We also show that Rab37 is phosphorylated by protein kinase Cα (PKCα) at threonine 172 (T172), leading to attenuation of its GTP-bound state, and impairment of the Rab37-mediated exocytosis of TIMP1, and thus reduces its suppression activity on lung cancer cell motility.	SIGNOR-273803
P49841	Q6NZ36	1	phosphorylation	down-regulates quantity	0.2	Furthermore, GSK3beta was able to decrease the cellular FAAP20 levels when overexpressed in wild-type, but not in FBW7 -/- HCT116 cells, indicating that GSK3beta requires downstream FBW7 to regulate the FAAP20 stability.\|GSK3\u03b2 phosphorylates FAAP20 at Ser113.	SIGNOR-279048
O95071	P48431	1	polyubiquitination	down-regulates quantity by destabilization	0.256	We identified UBR5 as a major ubiquitin E3 ligase that induces SOX2 degradation through ubiquitinating SOX2 at lysine 115.	SIGNOR-277446
Q9Y4K3	P68400	2	binding	up-regulates activity	0.2	Here, we show that somatic nuclear autoantigenic sperm protein (sNASP) binds to TRAF6 to prevent TRAF6 autoubiquitination in unstimulated macrophages. Following LPS stimulation, a complex consisting of sNASP, TRAF6, IRAK4, and casein kinase 2 (CK2) is formed. CK2 phosphorylates sNASP at serine 158, allowing sNASP to dissociate from TRAF6. Free TRAF6 is then autoubiquitinated, followed by activation of downstream signaling pathways.	SIGNOR-273656
Q8WVD3	P61086	2	binding	up-regulates activity	0.536	NARF exhibits E3 ubiquitin-ligase activity in cooperation with the ubiquitin conjugating enzyme, E2-25K. These data show that the auto-ubiquitylating activity of NARF is coordinated with E2-25K, and that the RING finger domain of NARF is indispensable for this reaction.	SIGNOR-271594
P35790	P35968	1	phosphorylation	down-regulates quantity by destabilization	0.249	Here, we show for the first time a possible mechanism by which CKI dependent phosphorylation of VEGFR2 at specific sites in its C-terminal tail triggers SCF beta-TRCP -mediated VEGFR2 ubiquitination and destruction.	SIGNOR-279029
Q9NQS7	P06493	0	phosphorylation	up-regulates	0.759	Here, we report that cdk1 phosphorylates thr 59 and thr 388 on inner centromere protein (incenp), which regulates the localization and kinase activity of aurora-b from prophase to metaphase. The replacement of endogenous incenp with t388a resulted in the delay of progression from metaphase to anaphase.	SIGNOR-143387
P10070	P48729	0	phosphorylation	down-regulates	0.568	Gli2 can also be phosphorylated directly by ck-1 at the non-optimal sites	SIGNOR-146112
O95837	P35368	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-257190
P20309	P08754	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
P08754	P49286	2	binding	up-regulates activity	0.452	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-256850
Q8IZJ0	Q08334	2	binding	up-regulates	0.697	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-96209
P00742	P08709	2	cleavage	up-regulates activity	0.541	The factor VII zymogen is cleaved at arginine 152 by a variety of proteases, including thrombin, factor IXa, factor Xa, and factor VIIa–tissue factor to produce the serine protease factor VIIa.	SIGNOR-263523
P14598	Q05513	0	phosphorylation	up-regulates	0.394	Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation.	SIGNOR-89280
P30550	P19086	2	binding	up-regulates activity	0.25	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257314
Q96B97	P22681	2	binding	up-regulates	0.747	The cin85 sh3 domains interact with c-cbl, an e3 ubiquitin ligase, via an unconventional pxxxpr ligand sequence, with the highest affinity displayed by the sh3-b domain. Interaction with cin85 recruits c-cbl to the amap1 complex where its ubiquitination activity is necessary for cancer cells to develop an invasive phenotype and to degrade the matrix.	SIGNOR-203139
P03372	Q01851	2	binding	up-regulates activity	0.552	The POU domain of Brn-3a and Brn-3b was shown to interact with the DNA-binding domain of the ER. Brn-3-ER interactions also affect transcriptional activity of an ERE-containing promoter, such that in estradiol-stimulated cells, Brn-3b strongly activated the promoter via the ERE, while Brn-3a had a mild inhibitory effect.	SIGNOR-241275
P49841	Q86YF9	1	phosphorylation	up-regulates activity	0.39	Phosphorylation of Dzip1 by GSK3\u03b2 Promotes the Release of Rab8 GDP from GDI2.	SIGNOR-278251
Q9Y297	P30304	1	ubiquitination	up-regulates	0.494	Scfb-trcp has recently been shown to degrade phosphorylated cdc25a in the s and g2 phases.	SIGNOR-128436
P49841	Q99684	1	phosphorylation	down-regulates quantity by destabilization	0.2	GSK3β-mediated GFI1 S94/S98 phosphorylation triggered its interaction with FBXW7, resulting in SCFFBXW7-mediated ubiquitination and degradation.	SIGNOR-277465
P35568	P45983	0	phosphorylation	down-regulates activity	0.771	Insulin also activates jnk, erk, pkc and mtor, which induce the phosphorylation of irs1 on serine residues 307, 612 and 632 and inhibit its functions. Our results indicate that the insulin-stimulated degradation of irs-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the ser(312) phosphorylation of irs-1.	SIGNOR-96948
P31749	P55265	1	phosphorylation	down-regulates activity	0.281	AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively	SIGNOR-276193
P15976	Q03112	0	transcriptional regulation	up-regulates quantity by expression	0.319	We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2	SIGNOR-266061
Q13618	Q99426	1	ubiquitination	down-regulates quantity	0.245	Gigaxonin is the substrate-specific adaptor for a new Cul3-E3-ubiquitin ligase family that promotes the proteasome dependent degradation of its partners MAP1B, MAP8 and tubulin cofactor B.	SIGNOR-268945
Q15025	Q13114	2	binding	down-regulates activity	0.432	ABIN1 interacted with the A20 regulatory molecule TAX1BP1 and was essential for the recruitment of TAX1BP1 and A20 to the noncanonical IkappaB kinases TBK1 and IKKi in response to poly(I:C) transfection. ABIN1 and TAX1BP1 together disrupted the interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKKi to attenuate lysine 63-linked polyubiquitination of TBK1/IKKi.	SIGNOR-275736
P31321	O43164	0	polyubiquitination	down-regulates quantity by destabilization	0.2	Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits	SIGNOR-271857
Q15672	Q9GZU7	0	dephosphorylation	down-regulates activity	0.2	These results indicate that SCP1 is the phosphatase that counter-regulates the MAPK-mediated phosphorylation of S68-Twist1.	SIGNOR-245962
P10636	Q16512	0	phosphorylation	down-regulates	0.329	Phosphorylation of tau is regulated by pknthere is a pkn-specific phosphorylation site, ser-320, in mbdsthus pkn serves as a regulator of microtubules by specific phosphorylation of tau, which leads to disruption of tubulin assembly.	SIGNOR-84958
Q01860	P31749	2	transcriptional regulation	down-regulates quantity by repression	0.457	Furthermore, in ECCs, unphosphorylated Oct4 bound to the AKT1 promoter and repressed its transcription.	SIGNOR-252635
Q15139	P63167	1	phosphorylation	down-regulates activity	0.2	We now provide evidence that PKD phosphorylates an additional site in DLC1, namely serine 807 within the GAP domain, adding another layer of complexity to PKD-mediated negative regulation of the DLC1 tumor suppressor protein.\|We previously reported that PKD inhibits DLC1 cellular function through phosphorylation of serines 327 and 431 [10].	SIGNOR-279265
Q9HB89	P50148	2	binding	up-regulates activity	0.492	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-256751
P16220	Q13627	0	phosphorylation	up-regulates activity	0.487	Regarding to the functional role of Dyrk1A, active Dyrk1A phosphorylates the transcription factor cAMP response element -binding protein (CREB), which subsequently leads to the stimulation of cAMP response element-mediated gene transcription during neuronal differentiation ( ).	SIGNOR-279989
Q05513	P14598	1	phosphorylation	up-regulates	0.394	Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation.	SIGNOR-89280
Q15797	P28482	0	phosphorylation	down-regulates	0.608	Phosphorylation of the linker region of smads mediated by erk2, gsk3?, And cdk2/4 negatively regulates smad activity by preventing their relocation to the nucleus, by inhibiting their interactions with coactivators, or by accelerating their degradation;in contrast, erk2 phosphorylated all four smad1 residues almost evenly, while showing a preference for s204 over s208 and s213 in smad3	SIGNOR-161597
P04839	P15976	0	transcriptional regulation	up-regulates quantity	0.279	These results suggest that GATA-1 is an activator and that GATA-2 is a relative competitive inhibitor of GATA-1 in the expression of the gp91(phox) gene in human eosinophils.	SIGNOR-259947
P63279	O14503	1	polyubiquitination	down-regulates quantity by destabilization	0.326	Co-expression of STRA13 and UBC9 led to an increase of the pSTRA13 ubiquitination and subsequent degradation. These data established that UBC9/STRA13 association in cells is of physiological importance, presenting direct proof of UBC9 involvement in the ubiquitin-dependent degradation of pSTRA13. We also checked whether UBC9 is directly involved in pSTRA13 ubiquitination. Taken together, these results strongly suggest that pSTRA13 is targeted for proteolysis by the ubiquitin-dependent proteasome pathway through association with UBC9.	SIGNOR-272579
P17252	O15519	1	phosphorylation	up-regulates quantity by stabilization	0.2	Here, we identify serine 193 as a novel in vivo phosphorylation site of all c-FLIP proteins. c-FLIP S193 phosphorylation is mediated by PKCa and PKCb.S193 phosphorylation increases the stability of the short c-FLIP proteins	SIGNOR-276147
P23470	P51813	1	dephosphorylation	down-regulates activity	0.26	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254693
Q14703	Q96BA8	1	cleavage	up-regulates	0.571	Cleavage of oasis by site-1 and site-2 proteases / oasis is cleaved at the membrane under er stress conditions and that its cleaved n-terminal domain translocates into the nucleus;and then activates transcription of target genes	SIGNOR-143785
Q99650	Q6EBC2	2	binding	up-regulates	0.615	Here we identify a four-helix bundle cytokine we have called interleukin 31 (il-31), which is preferentially produced by t helper type 2 cells. Il-31 signals through a receptor composed of il-31 receptor a and oncostatin m receptor.	SIGNOR-125347
Q14416	P63092	2	binding	up-regulates activity	0.358	MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.	SIGNOR-264079

Q9UI08

Q13976

0

phosphorylation

down-regulates activity

0.2

Vertebrate Ena/VASP proteins are phosphorylated by PKA, as well as PKG, and the phosphorylation is required for full function in a number of cellular contexts

SIGNOR-268290

Q96GD4

Q9UKV0

1

phosphorylation

down-regulates

0.262

We define the precise site of aurb-mediated phosphorylation as a conserved serine within the nuclear localization signals of hdac4, hdac5, and hdac9 at ser265, ser278, and ser242, respectivelyduring mitosis, aurb-mediated phosphorylation may localize class iia hdacs to a phosphorylation gradient at the spindle midzone, permitting temporal and spatial regulatory mechanisms altering hdac protein interactions

SIGNOR-198654

Q12834

Q5XUX0

2

binding

down-regulates quantity by destabilization

0.398

Here we show that the low levels of FBXO31 are maintained through proteasomal degradation by anaphase-promoting complex/cyclosome (APC/C). We find that the APC/C coactivators CDH1 and CDC20 bind to a destruction-box (D-box) motif present in FBXO31 to promote its polyubiquitination and degradation in a cell-cycle-regulated manner, which requires phosphorylation of FBXO31 on serine-33 by the prosurvival kinase AKT.

SIGNOR-277378

Q9H4A3

Q9H2X9

1

phosphorylation

down-regulates activity

0.461

The activity of the neuronal specific KCC2 had recently been shown to be regulated by the WNK1 kinase, where phosphorylation decreased KCC2 activation .|WNK1 phosphorylation of KCC2 occurs in immature neurons but is absent in adult neurons , , emphasizing a developmental role.

SIGNOR-280163

Q03060

P60568

1

transcriptional regulation

down-regulates quantity by repression

0.481

In this study we show that CREM is transcriptionally induced in T cells following stimulation through CD3 and CD28, binds to the IL-2 promoter in vivo, and suppresses IL-2 production.

SIGNOR-261576

O75116

Q15306

1

phosphorylation

up-regulates

0.417

Carock2 phosphorylated irf4 at either of 2 distinct phosphorylation sites, s446 and s447 / rock2-mediated phosphorylation of irf4 regulated the synthesis of il-17 and il-21 and the differentiation of th17 cells.

SIGNOR-167471

Q8IWU2

Q00535

0

phosphorylation

up-regulates

0.497

Here, we demonstrate that lmtk2 is phosphorylated on serine-1418 (lmtk2ser ) by cdk5/p35 and present evidence that this regulates its ability to phosphorylate pp1cthr __

SIGNOR-195329

P23458

P42226

1

phosphorylation

up-regulates activity

0.765

IL-4-stimulated Stat6 activation is mediated by Jak1 whereas Tyk2 is required for Stat6 activation in IL-13-treated monocytes

SIGNOR-249531

Q7LDG7

P28482

0

phosphorylation

down-regulates activity

0.396

ERK2 phosphorylates RasGRP2 at Ser394 located in the linker region implicated in its autoinhibition.

SIGNOR-279537

O75164

Q8NEZ5

0

ubiquitination

down-regulates quantity by destabilization

0.339

SCF(FBXO22) regulates histone H3 lysine 9 and 36 methylation levels by targeting histone demethylase KDM4A for ubiquitin-mediated proteasomal degradation

SIGNOR-273442

Q13164

Q15256

0

dephosphorylation

down-regulates activity

0.45

In this study we concentrated on whether and how PTP-SL, a kinase-interacting motif-containing PTP, might be involved in the down-regulation of the ERK5 signal|Whereas inactivation of ERK5 by PTP-SL monitored in vitro is most probably simply due to the dephosphorylation of tyrosine 220 in the activating TEY motif

SIGNOR-248721

O43541

Q13485

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

Q969V1

P63092

2

binding

up-regulates activity

0.25

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256795

P17302

P12931

0

phosphorylation

down-regulates

0.588

The oncogenic tyrosine kinase, v-src, phosphorylates connexin43 (cx43) on y247 and y265 and inhibits cx43 gap junctional communication (gjc), the process of intercellular exchange of ions and metabolites.

SIGNOR-148913

Q86UX7

P17252

0

phosphorylation

up-regulates activity

0.2

PKC-induced phosphorylation events, as we have shown kindlin-3 to be a PKC phosphorylation target (Fig. 6C), are often followed by rapid activation of phosphatases (38).

SIGNOR-266415

P06213

P54646

0

phosphorylation

up-regulates

0.372

Ampk phosphorylates and activates theinsulinreceptor, providing a direct link between ampk and theinsulin pathway.

SIGNOR-195324

P54764

P10912

1

phosphorylation

up-regulates activity

0.2

EphA4 binds to growth hormone receptor at both its extracellular and intracellular domains and phosphorylates growth hormone receptor when stimulated with a ligand.|These findings suggest that EphA4 activates not only GHR, as shown above, but also JAK2 by direct phosphorylation.

SIGNOR-279461

Q9UN37

Q9Y3E7

1

cleavage

up-regulates activity

0.625

Here, we show, using high-speed atomic force microscopy and electron microscopy, that the AAA-type adenosine triphosphatase VPS4 constricts and cleaves ESCRT-III CHMP2A-CHMP3 helical filaments in vitro. Our results demonstrate that VPS4 actively constricts ESCRT-III filaments and cleaves them before their complete disassembly. We propose that the formation of ESCRT-III dome-like end caps by VPS4 within a membrane neck structure constricts the membrane to set the stage for membrane fission.

SIGNOR-260847

Q02962

Q04727

2

binding

down-regulates activity

0.456

In cell culture, Grg4 suppresses Pax2-mediated transcriptional activation and inhibits phosphorylation of the Pax2 activation domain by WNT signaling and JNK

SIGNOR-251710

P30679

P41968

2

binding

up-regulates activity

0.272

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-257358

Q15208

Q2M2I8

1

phosphorylation

up-regulates activity

0.27

We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation. AAK1 phosphorylation regulates dendrite branching and length

SIGNOR-263034

P42345

P31749

2

phosphorylation

up-regulates activity

0.929

The rictor-mtor complex directly phosphorylated akt/pkb on ser473 in vitro and facilitated thr308 phosphorylation by pdk1

SIGNOR-252599

Q16512

P29966

1

phosphorylation

down-regulates activity

0.365

PRK1 phosphorylates MARCKS at the PKC sites: serine 152, serine 156 and serine 163.

SIGNOR-249671

P17612

P35612

1

phosphorylation

down-regulates activity

0.283

Ser-726 and Ser-713 in the C-terminal MARCKS-related domains of - and -adducin, respectively, were identified as the major phosphorylation sites common for PKA and PKC. Phosphorylation by PKA, but not PKC, reduced the affinity of adducin for spectrin-F-actin complexes as well as the activity of adducin in promoting binding of spectrin to F-actin.

SIGNOR-250332

Q9HBW0

O95837

2

binding

up-regulates activity

0.484

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-257431

Q969H0

O96020

2

binding

down-regulates quantity by destabilization

0.436

Cdk2 (S384) and GSK3 (T380) prime cyclin E for destruction. The hyper-phosphorylated T380/S384 degron has high affinity for monomeric Fbw7α, which engages the remainder of the SCF to initiate cyclin E's ubiquitination by an E2 enzyme

SIGNOR-271642

P17812

P17252

0

phosphorylation

down-regulates

0.2

These data indicated that protein kinase c phosphorylation at ser(462) stimulates human ctp synthetase 1 activity, whereas phosphorylation at thr(455) inhibits activity.

SIGNOR-154621

Q9HB63

Q6ZN44

2

binding

up-regulates

0.61

The unc5hs are axon guidance receptors that mediate netrin-1-dependent chemorepulsion, and dependence receptors that mediate netrin-1-independent apoptosis.

SIGNOR-98483

P06241

P43146

1

phosphorylation

up-regulates activity

0.572

Fyn tyrosine kinase, but not Src, regulates the phosphorylation of DCC in N1E-115 neuroblastoma cells.Both DCC phosphorylation and Netrin-1-induced axon outgrowth are impaired in Fyn(-/-) CN and spinal cord explants. We propose that DCC is regulated by tyrosine phosphorylation and that Fyn is essential for the response of axons to Netrin-1. these results show that DCC is phosphorylated by Fyn, but not Src, in N1E-115 cells, and that tyrosines 1261 and 1418 are the major phosphorylation sites of Fyn in vivo.

SIGNOR-268176

O75581

O14640

2

binding

up-regulates activity

0.707

The Wnt–FZD–LRP5/6 trimeric complex recruits Dishevelled (DVL) and Axin through the intracellular domains of FZD and LRP5/6, resulting in inhibition of β-catenin phosphorylation and thus ensuing β-catenin stabilization.

SIGNOR-262526

O95835

P35240

2

binding

up-regulates

0.689

As expected, the nf2-/- fc-912 cells were defective in lats1/2 phosphorylation (figure s2e-f). Subcellular fractionation revealed a significant increase of endogenous lats1/2 in the cytoplasmic relative to the membrane fraction in the nf2-/- fc-912 schwann cells compared to the nf2+/+ fh-912 schwann cells (figure 2e). This localization defect was rescued by re-expression of nf2

SIGNOR-202604

P38405

Q5NUL3

2

binding

up-regulates activity

0.25

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

SIGNOR-256916

Q9UL54

P19419

1

phosphorylation

up-regulates activity

0.31

Transfection studies demonstrated that TAO2 stimulates phosphorylation of the TCF Elk1 on the major activating site, Ser383, and that TAO2 stimulates transactivation of Elk1 and the related TCF, Sap1.

SIGNOR-246638

Q9Y5H1

Q9Y5H9

2

binding

up-regulates activity

0.2

The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.

SIGNOR-265691

Q14145

Q13618

2

binding

up-regulates activity

0.95

Keap1 is a BTB-Kelch protein that functions as a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex. Keap1 targets its substrate, the Nrf2 transcription factor, for ubiquitination and subsequent degradation by the 26 S proteasome. The N-terminal BTB domain and central linker region of Keap1 bind Cul3, whereas the C-terminal Kelch domain of Keap1 binds Nrf2 via residues located within loops that extend out from the bottom of the Kelch domain

SIGNOR-268925

Q6Y7W6

Q92600

2

binding

up-regulates activity

0.2

Through interaction analysis of RQCD1 with full-length or partial proteins of GIGYF1 and GIGYF2, segments corresponding to 620-665th and 667-712th amino acids were identified as potential interacting regions on GIGYF1 and GIGYF2, respectively, with RQCD1. we found that RQCD1 was required for enhancement of the interaction of Grb10 with GIGYF1 and GIGYF2

SIGNOR-260058

Q8IUQ4

Q13535

0

phosphorylation

down-regulates activity

0.2

We have also demonstrated that DNA damage triggers disruption of the HIPK2-Siah-1 complex, resulting in HIPK2 stabilization and activation. Disruption of the HIPK2-Siah-1 complex is mediated by the ATM/ATR pathway and involves ATM/ATR-dependent phosphorylation of Siah-1 at Ser 19.

SIGNOR-276167

P23528

Q8WYL5

0

dephosphorylation

up-regulates activity

0.786

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

SIGNOR-248762

Q99704

P06239

0

phosphorylation

up-regulates activity

0.6

Phosphorylation of p56 dok and p62 dok is increased following CD2 stimulation and requires Lck. Phosphorylation of Dok proteins by Lck might provide a mechanism by which SH2-containing proteins can be recruited and co-localized with their substrates.

SIGNOR-251373

Q15120

P08559

1

phosphorylation

down-regulates activity

0.871

Activity of the mammalian pyruvate dehydrogenase complex is regulated by phosphorylation-dephosphorylation of the alpha subunit of the pyruvate dehydrogenase (e1) component. Phosphorylation is carried out by four pyruvate dehydrogenase kinase (pdk) isoenzymes.

SIGNOR-109647

P51617

Q9HAT8

2

phosphorylation

up-regulates activity

0.781

The phosphorylation of Pellino2 by activated IRAK1 and IRAK4 could trigger and modulate the translocation of IRAKs from complex I to complex II.

SIGNOR-278947

P11511

Q13285

0

transcriptional regulation

up-regulates quantity by expression

0.479

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-271787

Q86YT6

P78504

1

ubiquitination

up-regulates activity

0.693

Mib1 is essential for the generation of functional notch ligands and regulates the classical notch ligands dll1, dll4, jag1, and jag2 in vertebrates mib1 is an essential e3 ubiquitin ligase for jag1 in the developing cerebellum.

SIGNOR-97388

P17612

P06241

2

phosphorylation

up-regulates

0.459

The serine 21 (s21) residue of fyn is a protein kinase a (pka) recognition site within an rxxs motif of the amino terminal sh4 domain of fyn. In addition, s21 is critical for fyn kinase-linked cellular signaling. Mutation of s21a blocks pka phosphorylation of fyn and alters its tyrosine kinase activity.

SIGNOR-167147

P28482

P07949

0

phosphorylation

up-regulates

0.423

We hypothesized that ret could directly phosphorylate fak and erk. erk 2 could be phosphorylated at y187 (y204 in erk1).

SIGNOR-140294

P24928

O00308

0

ubiquitination

down-regulates quantity

0.387

WWP2 ubiquitylates RNA polymerase II for DNA-PK-dependent transcription arrest and repair at DNA breaks|In response to DSBs, WWP2 targets the RNAPII subunit RPB1 for K48-linked ubiquitylation, thereby driving DNA-PK- and proteasome-dependent eviction of RNAPII.

SIGNOR-268851

P41236

Q13315

0

phosphorylation

down-regulates

0.2

Atm phosphorylates i-2 on serine 43, leading to the dissociation of the pp1-i-2 complex and the activation of pp1.

SIGNOR-160648

O75144

P05771

0

phosphorylation

up-regulates activity

0.2

PKCα and PKCβ are required for phosphorylation of ICOSL and ICOSL-mediated cytokine induction

SIGNOR-273797

P10275

P06493

0

phosphorylation

up-regulates

0.53

At first, the data show that cdk5 enables phosphorylation of ar at ser-81 site through direct biochemical interaction and, therefore, results in the stabilization of ar proteins although ar was reported as substrates for cdk9 (5) as well as cdk1

SIGNOR-175692

Q9Y6N7

P00519

0

phosphorylation

down-regulates

0.606

Abl functions to antagonize robo signaling both abl and ena can directly bind to robo's cytoplasmic domain.

SIGNOR-78993

P53350

Q2M2Z5

1

phosphorylation

up-regulates

0.519

Here, we identify a novel centrosomal substrate of plk1, kizuna (kiz), depletion of which causes fragmentation and dissociation of the pericentriolar material from centrioles at prometaphase, resulting in multipolar spindles. Plk1 maintains the integrity of the spindle poles by phosphorylating kiz.

SIGNOR-149630

Q96SB4

Q9Y5S9

1

phosphorylation

down-regulates

0.261

We demonstrate that y14 is phosphorylated at its repeated arginine/serine (rs) dipeptides, likely by sr protein-specific kinases. Phosphorylation of y14 abolished its interaction with ejc components as well as factors that function downstream of the ejc.

SIGNOR-139555

P29803

Q15119

0

phosphorylation

down-regulates

0.548

Kinetic and regulatory properties of recombinant human pdh2 and pdh1 were compared in this study. Site-specific phosphorylation/dephosphorylation of the three phosphorylation sites by four pdh kinases (pdk1-4) and two pdh phosphatases (pdp1-2) were investigated by substituting serines with alanine or glutamate in pdhs.

SIGNOR-143970

P35638

P68400

0

phosphorylation

down-regulates activity

0.344

CHOP transcription factor phosphorylation by casein kinase 2 inhibits transcriptional activation. | The serine to alanine substituted site CHOP mutant was not phosphorylated by CK2, indicating that serines 14–15 and 30–31 of CHOP are the CK2 phosphoacceptor sites

SIGNOR-250850

Q16637

Q93008

0

deubiquitination

up-regulates quantity by stabilization

0.28

Ubiquitin-specific Protease 9x Deubiquitinates and Stabilizes the Spinal Muscular Atrophy Protein-Survival Motor Neuron

SIGNOR-253113

Q15139

Q92481

1

phosphorylation

down-regulates activity

0.295

Mechanistically, we observed that PKD phosphorylates AP2\u03b2 at Ser-258 and Ser-277 and suppresses its nuclear accumulation.|Using ChIP analyses, here we found that PKD knockdown in HUVECs increases binding of AP2beta to the VEGFR-2 promoter.

SIGNOR-279267

O14757

Q08050

1

phosphorylation

up-regulates activity

0.371

In addition, upon treatment with genotoxic agents, the checkpoint kinases Chk1 and Chk2 also phosphorylate and activate FOXM1.

SIGNOR-280224

O95379

P63096

2

binding

up-regulates activity

0.2

TNFAIP8: a new effector for Galpha(i) coupling to reduce cell death and induce cell transformation

SIGNOR-256491

Q15361

Q9GZV5

2

binding

up-regulates

0.313

Taz is a coactivator for pax8 and ttf-1, two transcription factors involved in thyroid differentiation. / we show that this interaction leads to a significant enhancement of the transcriptional activity of pax8 and ttf-1 on the thyroglobulin promoter thus suggesting a role of taz in the control of genes involved in thyroid development and differentiation.

SIGNOR-182296

Q96AX2

P17252

0

phosphorylation

down-regulates activity

0.2

We also show that Rab37 is phosphorylated by protein kinase Cα (PKCα) at threonine 172 (T172), leading to attenuation of its GTP-bound state, and impairment of the Rab37-mediated exocytosis of TIMP1, and thus reduces its suppression activity on lung cancer cell motility.

SIGNOR-273803

P49841

Q6NZ36

1

phosphorylation

down-regulates quantity

0.2

Furthermore, GSK3beta was able to decrease the cellular FAAP20 levels when overexpressed in wild-type, but not in FBW7 -/- HCT116 cells, indicating that GSK3beta requires downstream FBW7 to regulate the FAAP20 stability.|GSK3\u03b2 phosphorylates FAAP20 at Ser113.

SIGNOR-279048

O95071

P48431

1

polyubiquitination

down-regulates quantity by destabilization

0.256

We identified UBR5 as a major ubiquitin E3 ligase that induces SOX2 degradation through ubiquitinating SOX2 at lysine 115.

SIGNOR-277446

Q9Y4K3

P68400

2

binding

up-regulates activity

0.2

Here, we show that somatic nuclear autoantigenic sperm protein (sNASP) binds to TRAF6 to prevent TRAF6 autoubiquitination in unstimulated macrophages. Following LPS stimulation, a complex consisting of sNASP, TRAF6, IRAK4, and casein kinase 2 (CK2) is formed. CK2 phosphorylates sNASP at serine 158, allowing sNASP to dissociate from TRAF6. Free TRAF6 is then autoubiquitinated, followed by activation of downstream signaling pathways.

SIGNOR-273656

Q8WVD3

P61086

2

binding

up-regulates activity

0.536

NARF exhibits E3 ubiquitin-ligase activity in cooperation with the ubiquitin conjugating enzyme, E2-25K. These data show that the auto-ubiquitylating activity of NARF is coordinated with E2-25K, and that the RING finger domain of NARF is indispensable for this reaction.

SIGNOR-271594

P35790

P35968

1

phosphorylation

down-regulates quantity by destabilization

0.249

Here, we show for the first time a possible mechanism by which CKI dependent phosphorylation of VEGFR2 at specific sites in its C-terminal tail triggers SCF beta-TRCP -mediated VEGFR2 ubiquitination and destruction.

SIGNOR-279029

Q9NQS7

P06493

0

phosphorylation

up-regulates

0.759

Here, we report that cdk1 phosphorylates thr 59 and thr 388 on inner centromere protein (incenp), which regulates the localization and kinase activity of aurora-b from prophase to metaphase. The replacement of endogenous incenp with t388a resulted in the delay of progression from metaphase to anaphase.

SIGNOR-143387

P10070

P48729

0

phosphorylation

down-regulates

0.568

Gli2 can also be phosphorylated directly by ck-1 at the non-optimal sites

SIGNOR-146112

O95837

P35368

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-257190

P20309

P08754

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

P08754

P49286

2

binding

up-regulates activity

0.452

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-256850

Q8IZJ0

Q08334

2

binding

up-regulates

0.697

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-96209

P00742

P08709

2

cleavage

up-regulates activity

0.541

The factor VII zymogen is cleaved at arginine 152 by a variety of proteases, including thrombin, factor IXa, factor Xa, and factor VIIa–tissue factor to produce the serine protease factor VIIa.

SIGNOR-263523

P14598

Q05513

0

phosphorylation

up-regulates

0.394

Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation.

SIGNOR-89280

P30550

P19086

2

binding

up-regulates activity

0.25

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

SIGNOR-257314

Q96B97

P22681

2

binding

up-regulates

0.747

The cin85 sh3 domains interact with c-cbl, an e3 ubiquitin ligase, via an unconventional pxxxpr ligand sequence, with the highest affinity displayed by the sh3-b domain. Interaction with cin85 recruits c-cbl to the amap1 complex where its ubiquitination activity is necessary for cancer cells to develop an invasive phenotype and to degrade the matrix.

SIGNOR-203139

P03372

Q01851

2

binding

up-regulates activity

0.552

The POU domain of Brn-3a and Brn-3b was shown to interact with the DNA-binding domain of the ER. Brn-3-ER interactions also affect transcriptional activity of an ERE-containing promoter, such that in estradiol-stimulated cells, Brn-3b strongly activated the promoter via the ERE, while Brn-3a had a mild inhibitory effect.

SIGNOR-241275

P49841

Q86YF9

1

phosphorylation

up-regulates activity

0.39

Phosphorylation of Dzip1 by GSK3\u03b2 Promotes the Release of Rab8 GDP from GDI2.

SIGNOR-278251

Q9Y297

P30304

1

ubiquitination

up-regulates

0.494

Scfb-trcp has recently been shown to degrade phosphorylated cdc25a in the s and g2 phases.

SIGNOR-128436

P49841

Q99684

1

phosphorylation

down-regulates quantity by destabilization

0.2

GSK3β-mediated GFI1 S94/S98 phosphorylation triggered its interaction with FBXW7, resulting in SCFFBXW7-mediated ubiquitination and degradation.

SIGNOR-277465

P35568

P45983

0

phosphorylation

down-regulates activity

0.771

Insulin also activates jnk, erk, pkc and mtor, which induce the phosphorylation of irs1 on serine residues 307, 612 and 632 and inhibit its functions. Our results indicate that the insulin-stimulated degradation of irs-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the ser(312) phosphorylation of irs-1.

SIGNOR-96948

P31749

P55265

1

phosphorylation

down-regulates activity

0.281

AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively

SIGNOR-276193

P15976

Q03112

0

transcriptional regulation

up-regulates quantity by expression

0.319

We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2

SIGNOR-266061

Q13618

Q99426

1

ubiquitination

down-regulates quantity

0.245

Gigaxonin is the substrate-specific adaptor for a new Cul3-E3-ubiquitin ligase family that promotes the proteasome dependent degradation of its partners MAP1B, MAP8 and tubulin cofactor B.

SIGNOR-268945

Q15025

Q13114

2

binding

down-regulates activity

0.432

ABIN1 interacted with the A20 regulatory molecule TAX1BP1 and was essential for the recruitment of TAX1BP1 and A20 to the noncanonical IkappaB kinases TBK1 and IKKi in response to poly(I:C) transfection. ABIN1 and TAX1BP1 together disrupted the interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKKi to attenuate lysine 63-linked polyubiquitination of TBK1/IKKi.

SIGNOR-275736

P31321

O43164

0

polyubiquitination

down-regulates quantity by destabilization

0.2

Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits

SIGNOR-271857

Q15672

Q9GZU7

0

dephosphorylation

down-regulates activity

0.2

These results indicate that SCP1 is the phosphatase that counter-regulates the MAPK-mediated phosphorylation of S68-Twist1.

SIGNOR-245962

P10636

Q16512

0

phosphorylation

down-regulates

0.329

Phosphorylation of tau is regulated by pknthere is a pkn-specific phosphorylation site, ser-320, in mbdsthus pkn serves as a regulator of microtubules by specific phosphorylation of tau, which leads to disruption of tubulin assembly.

SIGNOR-84958

Q01860

P31749

2

transcriptional regulation

down-regulates quantity by repression

0.457

Furthermore, in ECCs, unphosphorylated Oct4 bound to the AKT1 promoter and repressed its transcription.

SIGNOR-252635

Q15139

P63167

1

phosphorylation

down-regulates activity

0.2

We now provide evidence that PKD phosphorylates an additional site in DLC1, namely serine 807 within the GAP domain, adding another layer of complexity to PKD-mediated negative regulation of the DLC1 tumor suppressor protein.|We previously reported that PKD inhibits DLC1 cellular function through phosphorylation of serines 327 and 431 [10].

SIGNOR-279265

Q9HB89

P50148

2

binding

up-regulates activity

0.492

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-256751

P16220

Q13627

0

phosphorylation

up-regulates activity

0.487

Regarding to the functional role of Dyrk1A, active Dyrk1A phosphorylates the transcription factor cAMP response element -binding protein (CREB), which subsequently leads to the stimulation of cAMP response element-mediated gene transcription during neuronal differentiation ( ).

SIGNOR-279989

Q05513

P14598

1

phosphorylation

up-regulates

0.394

Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation.

SIGNOR-89280

Q15797

P28482

0

phosphorylation

down-regulates

0.608

Phosphorylation of the linker region of smads mediated by erk2, gsk3?, And cdk2/4 negatively regulates smad activity by preventing their relocation to the nucleus, by inhibiting their interactions with coactivators, or by accelerating their degradation;in contrast, erk2 phosphorylated all four smad1 residues almost evenly, while showing a preference for s204 over s208 and s213 in smad3

SIGNOR-161597

P04839

P15976

0

transcriptional regulation

up-regulates quantity

0.279

These results suggest that GATA-1 is an activator and that GATA-2 is a relative competitive inhibitor of GATA-1 in the expression of the gp91(phox) gene in human eosinophils.

SIGNOR-259947

P63279

O14503

1

polyubiquitination

down-regulates quantity by destabilization

0.326

Co-expression of STRA13 and UBC9 led to an increase of the pSTRA13 ubiquitination and subsequent degradation. These data established that UBC9/STRA13 association in cells is of physiological importance, presenting direct proof of UBC9 involvement in the ubiquitin-dependent degradation of pSTRA13. We also checked whether UBC9 is directly involved in pSTRA13 ubiquitination. Taken together, these results strongly suggest that pSTRA13 is targeted for proteolysis by the ubiquitin-dependent proteasome pathway through association with UBC9.

SIGNOR-272579

P17252

O15519

1

phosphorylation

up-regulates quantity by stabilization

0.2

Here, we identify serine 193 as a novel in vivo phosphorylation site of all c-FLIP proteins. c-FLIP S193 phosphorylation is mediated by PKCa and PKCb.S193 phosphorylation increases the stability of the short c-FLIP proteins

SIGNOR-276147

P23470

P51813

1

dephosphorylation

down-regulates activity

0.26

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254693

Q14703

Q96BA8

1

cleavage

up-regulates

0.571

Cleavage of oasis by site-1 and site-2 proteases / oasis is cleaved at the membrane under er stress conditions and that its cleaved n-terminal domain translocates into the nucleus;and then activates transcription of target genes

SIGNOR-143785

Q99650

Q6EBC2

2

binding

up-regulates

0.615

Here we identify a four-helix bundle cytokine we have called interleukin 31 (il-31), which is preferentially produced by t helper type 2 cells. Il-31 signals through a receptor composed of il-31 receptor a and oncostatin m receptor.

SIGNOR-125347

Q14416

P63092

2

binding

up-regulates activity

0.358

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

SIGNOR-264079