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
P63096	P25101	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-257052
P50539	P61244	2	binding	up-regulates activity	0.558	The role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences.	SIGNOR-240314
Q969Q1	P55036	1	polyubiquitination	down-regulates quantity by destabilization	0.403	S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s. Surprisingly, the same four Lys residues on S5a, Lys-74, Lys-122, Lys-262, and Lys-365 were ubiquitinated by MuRF1 and E6AP (Fig. 10).	SIGNOR-272741
Q14689	Q12841	2	binding	up-regulates activity	0.48	We identified DIP2A as a novel FSTL1-binding partner from the membrane fraction of endothelial cells. Co-immunoprecipitation assays revealed a direct physical interaction between FSTL1 and DIP2A. The work in the current study identifies DIP2A as a novel receptor for FSTL1 that mediates Akt activation and cell survival and function in cardiovascular cells in vitro.	SIGNOR-266603
P46108	P09619	2	binding	up-regulates	0.609	Crk could bind to both pdgf alpha- and beta-receptors in vivo	SIGNOR-75884
P25105	P63092	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 ‚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-256789
P53367	Q15139	0	phosphorylation	up-regulates	0.385	We report that arfaptins contain an amphipathic helix (ah) preceding the bar domain, which is essential for their binding to phosphatidylinositol 4-phosphate (pi(4)p)-containing liposomes and the tgn of mammalian cells. The binding of arfaptin1, but not arfaptin2, to pi(4)p is regulated by protein kinase d (pkd) mediated phosphorylation at ser100 within the ah. We also found that only arfaptin1 is required for the pkd-dependent trafficking of chromogranin a by the regulated secretory pathway.	SIGNOR-202101
O60216	Q8N3U4	2	binding	up-regulates quantity by stabilization	0.965	Cohesin is an evolutionarily conserved complex composed of four core proteins (SMC1A, SMC3, RAD21 and either STAG2 or STAG1) that form a ring-shaped structure able to encircle chromatin	SIGNOR-261511
Q06413	P35580	1	transcriptional regulation	up-regulates quantity by expression	0.345	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238769
O75293	Q9UQ88	2	binding	down-regulates activity	0.2	Western blot analysis for SPDEF revealed that overexpression of GADD45α, β and γ prevents SPDEF degradation mediated by CDK11p58 \|We identified CDK11p58 as an interaction partner of GADD45α by co-immunoprecipitation analysis. We corroborated these data by co-immunoprecipitation in vitro translation assays, showing that all three members of the GADD45 family interact with CDK11p58.	SIGNOR-273024
P19525	P06493	1	phosphorylation	down-regulates	0.328	Our findings demonstrate that (i) pkr, ser/thr kinase, phosphorylates its new substrate cdc2 at the tyr 4 residue, (ii) pkr-mediated tyr 4-phosphorylation facilitates cdc2 ubiquitination and proteosomal degradation	SIGNOR-164809
P46934	Q13501	1	ubiquitination	down-regulates quantity by destabilization	0.277	Depletion of NEDD4 dramatically reduced the LC3 protein level and elevated the SQSTM1 protein level.\|Furthermore, SQSTM1 is ubiquitinated by NEDD4 while LC3 functions as an activator of NEDD4 ligase activity.	SIGNOR-278637
P48729	Q2M2I3	2	binding	up-regulates quantity	0.2	We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.	SIGNOR-273750
Q16539	P41970	1	phosphorylation	up-regulates	0.379	Tcf sap-1a is efficiently phosphorylated by p38 map kinase in vitro and in vivo on the homologous residues ser381 and ser387. Mutation of these sites to alanine severely reduces c-fos sre-dependent transcription mediated by sap-1a and p38 map kinase.	SIGNOR-47685
Q86TM6	P60484	1	ubiquitination	down-regulates quantity by destabilization	0.2	Secondly, HRD1 promotes PTEN ubiquitination and degradation.	SIGNOR-278724
O00506	P46937	1	phosphorylation	up-regulates activity	0.265	Collectively, our data demonstrate that loss of STK25 promotes YAP/TAZ activation.\|Lastly, we assessed if STK25 is able to promote YAP phosphorylation in the absence of LATS-HM phosphorylation, based on our in vitro kinase assay results.	SIGNOR-278993
Q01860	Q6U7Q0	0	transcriptional regulation	up-regulates quantity by expression	0.2	Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays revealed that Zfp322a binds to Pou5f1 and Nanog promoters and regulates their transcription.	SIGNOR-264900
P10915	P14780	0	cleavage	down-regulates quantity by destabilization	0.341	Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix.	SIGNOR-256328
P31749	P12931	0	phosphorylation	up-regulates activity	0.677	Regulation of Akt/PKB Activation by Tyrosine PhosphorylationAs shown in Fig. 2 d, while mutation of Tyr340 has little effect on either tyrosine phosphorylation or kinase activity of Akt induced by Src527F, substitution of Tyr315 or Tyr326 with a phenylalanine, respectively, dramatically reduces both the tyrosine phosphorylation and kinase activity of Akt. The combination of these two mutations abolishes Src-induced tyrosine phosphorylation of Akt as well as its kinase activity.	SIGNOR-252623
O14920	P54646	0	phosphorylation	up-regulates	0.257	These results demonstrate that the ikk is a direct substrate of ampk_2 and that its phosphorylation on ser177 and ser181no initiates the activation of the ampk_2 in endothelial cells which in turn phosphorylates and activates the _-subunit of the ikk. The latter also induces a higher rate of ikk auto-inactivation and thus attenuates the activation of nf_b and the expression of inflammatory genes	SIGNOR-174405
O15105	Q9Y5K5	2	binding	up-regulates	0.662	Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases.	SIGNOR-138879
P0DPK2	Q92830	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-269597
Q12809	Q15139	0	phosphorylation	down-regulates activity	0.2	Based on LC-MS results from in vivo and HEK293 cell experiments we chose four KV11.1 mutant candidates for further functional analysis. Ablation of the putative PKD phosphorylation site in the mutant S284A increased the maximal current indicating S284 as a main PKD target in KV11.1.	SIGNOR-277612
P32519	P67775	0	dephosphorylation	down-regulates activity	0.2	Elf-1 enhances the expression of CD3zeta, whereas it suppresses the expression of FcRgamma gene and lupus T cells have decreased amounts of DNA-binding 98 kDa form of Elf-1. We show that the aberrantly increased PP2A in lupus T cells dephosphorylates Elf-1 at Thr-231. Dephosphorylation results in limited expression and binding of the 98 kDa Elf-1 form to the CD3zeta and FcRgamma promoters. Suppression of the expression of the PP2A leads to increased expression of CD3zeta and decreased expression of FcRgamma genes and correction of the early signaling response	SIGNOR-248634
Q9C0F0	O60341	2	binding	down-regulates activity	0.266	Here, we showed that ASXL3 interacts with HP1α and LSD1, leading to transcriptional repression.	SIGNOR-266764
O75143	Q8TDY2	2	binding	up-regulates	0.919	Atg13 directly binds fip200.	SIGNOR-184120
P35568	Q04759	0	phosphorylation	down-regulates activity	0.567	Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101).	SIGNOR-260906
P21246	Q9UM73	2	binding	up-regulates	0.547	We conclude from this series of experiments that ptn specifically binds to the alk orphan receptor as a high affinity ligand at least in part via the putative ligand binding domain described above.	SIGNOR-106411
P05154	P02751	2	binding	down-regulates activity	0.312	SERPINA5 inhibits HCC cell migration by directly interacting with fibronectin. SERPINA5 disrupts the fibronectin–integrin β1 signaling pathway.	SIGNOR-265881
P12931	P35916	1	phosphorylation	up-regulates	0.513	Vegfr-3 is a direct c-src target and mass spectrometry analysis identified the sites phosphorylated by c-src as tyrosine 830, 833, 853, 1063, 1333, and 1337 vegfr-3 phosphorylation activates the recruitment to the receptor of the adaptor proteins crki/ii and shc inducing activation of jnk.	SIGNOR-165035
P49336	P84022	1	phosphorylation	down-regulates	0.566	Similarly, tgf-?-Induced and cdk8/9-mediated phosphorylation of smad3 at threonine 179 (t179) is important for binding of the nedd4l e3 ubiquitin ligase, which accelerates smad3 turnover;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3.	SIGNOR-161557
Q15418	P28482	0	phosphorylation	up-regulates activity	0.759	Several lines of evidence indicate that the mapkap-k1 isoforms are also activated by mapks in vivo via the ras-dependent protein kinase cascade that is triggered by growth factors or tumor-promoting phorbol esters, such as phorbol 12-myristate 13-acetate (pma). here we identify six sites in mapkap-k1a that become phosphorylated in transfected cos-1 cells. The inactive form of mapkap-k1a in unstimulated cells is partially phosphorylated at ser222 and ser733. Stimulation with phorbol 12-myristate 13-acetate induces the phosphorylation of thr360, ser364, thr574, and ser381 and increases the phosphorylation of ser222 and ser733.	SIGNOR-219308
P30307	P06493	2	dephosphorylation	up-regulates	0.858	Cdk1/cdc2 activation involves tyr15/thr14 dephosphorylation by cdc25c	SIGNOR-186621
P31749	Q9Y4P1	1	phosphorylation	up-regulates activity	0.31	In this study, we identified a novel phosphorylation site at Ser34 of ATG4B induced by AKT in HCC cells.\| In brief, our results demonstrate for the first time that the phosphorylation of ATG4B at Ser34 participates in the metabolic reprogramming of HCC cells via repressing mitochondrial function, which possibly results from the Ser34 phosphorylation-induced mitochondrial enrichment of ATG4B and the subsequent inhibition of F1Fo-ATP synthase activity.	SIGNOR-275834
Q06413	Q9UKV0	2	binding	down-regulates	0.633	Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent manner	SIGNOR-235642
P02545	Q9UH99	1	relocalization	up-regulates activity	0.622	In the case of Sun2, there is some evidence that A-type lamins might contribute to Sun2 localization in the INM. We report that an interaction between subunits of the HOPS complex and the ERM (ezrin, radixin, moesin) proteins is required for the delivery of EGF receptor (EGFR) to lysosomes. Inhibiting either ERM proteins or the HOPS complex leads to the accumulation of the EGFR into early endosomes, delaying its degradation.	SIGNOR-261310
Q14833	P63092	2	binding	up-regulates activity	0.344	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-264082
Q96J02	Q12778	1	ubiquitination	down-regulates quantity by destabilization	0.258	Mechanistically, Itch ubiquitinates Foxo1 for proteasomal degradation.	SIGNOR-278698
P63000	Q8N103	0	gtpase-activating protein	down-regulates activity	0.402	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260524
Q92598	P19784	0	phosphorylation	down-regulates activity	0.327	Protein kinase CK2 phosphorylates Hsp105 alpha at Ser509 and modulates its function. \| the phosphorylation of Hsp105 alpha at Ser(509) abolished the inhibitory activity of Hsp105 alpha in vitro.	SIGNOR-251008
P67775	P23443	1	dephosphorylation	down-regulates	0.72	Protein phosphatase 2a inactivates the mitogen-stimulated s6 kinase from swiss mouse 3t3 cells	SIGNOR-23575
P04637	Q9HCI7	0	ubiquitination	down-regulates activity	0.37	Here we describe MSL2, a novel E3 ligase for p53 that promotes ubiquitin-dependent cytoplasmic p53 localization. Unlike Mdm2 or most other p53 E3 ligases, MSL2-mediated p53 ubiquitination does not affect the stability of p53. Moreover, the MSL2-mediated effect on p53 is Mdm2-independent. Thus, our study identifies an important ubiquitin-ligase for modulating p53 subcellular localization. MSL2 ubiquitination of p53 is required for p53 cytoplasmic localization.	SIGNOR-271774
Q02156	P11362	1	phosphorylation	up-regulates	0.2	Phosphorylation of serine 779 in fibroblast growth factor receptor 1 and 2 by protein kinase c(epsilon) regulates ras/mitogen-activated protein kinase signaling and neuronal differentiationour findings show that in addition to fgfr tyrosine phosphorylation, the phosphorylation of a conserved serine residue, ser(779), can quantitatively control ras/mapk signaling to promote specific cellular responses.	SIGNOR-201671
Q9NYJ8	Q9Y4K3	2	binding	up-regulates activity	0.933	The irak1/traf6 complex can also activate jnk and p38 signalling through assembly of a catalytically active tab2-tab3-tak1 complex.	SIGNOR-205458
P42261	Q13555	0	phosphorylation	up-regulates activity	0.63	In this study, CaM-kinase II enhanced kainate currents of expressed glutamate receptor 6 in 293 cells and of wild-type glutamate receptor 1, but not the Ser-627 to Ala mutant, in Xenopus oocytes. \| This CaM-kinase II regulatory phosphorylation site is conserved in all AMPA/kainate-type glutamate receptors, and its phosphorylation may be important in enhancing postsynaptic responsiveness as occurs during synaptic plasticity.	SIGNOR-250697
P31314	P06400	2	binding	down-regulates activity	0.2	ectopic HOX11 expression resulted in hyperphosphorylation of the retinoblastoma protein (Rb), which correlated with inhibition of the major Rb serine/threonine phosphatase PP1.	SIGNOR-240725
Q13950	P84022	2	binding	down-regulates activity	0.738	Tgf-beta inhibited the expression of the cbfa1 and osteocalcin genes, whose expression is controlled by cbfa1 in osteoblast-like cell lines. This inhibition was mediated by smad3, which interacts physically with cbfa1 and represses its transcriptional activity at the cbfa1-binding ose2 promoter sequence.	SIGNOR-235902
Q06210	P17252	0	phosphorylation	down-regulates activity	0.307	Phosphorylation of human glutamine:fructose-6-phosphate amidotransferase by cAMP-dependent protein kinase at serine 205 blocks the enzyme activity.	SIGNOR-249040
Q6IQ49	Q9NZJ0	2	binding	down-regulates quantity by destabilization	0.282	Here, we identify human SDE2 as a new genome surveillance factor regulated by PCNA interaction. The cleaved SDE2 products need to be degraded by the CRL4CDT2 ubiquitin E3 ligase in a cell cycle- and DNA damage-dependent manner, and failure to degrade SDE2 impairs S phase progression and cellular survival.	SIGNOR-272807
Q9NY46	Q92914	2	binding	down-regulates activity	0.2	Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.	SIGNOR-253446
P27695	Q00987	0	ubiquitination	down-regulates quantity by destabilization	0.416	Once the reaction proceeds beyond the monoubiquitination stage, MDM2 polyubiquitinates APE1 for degradation.	SIGNOR-278555
Q9UL17	P60568	1	transcriptional regulation	down-regulates quantity by repression	0.473	T-bet Transactivates the IFNγ Gene and Represses the IL-2 Gene in EL4 Cells	SIGNOR-266233
Q02962	O75688	0	dephosphorylation	down-regulates activity	0.2	PPM1B can dephosphorylate the Pax2 activation domain and displace the adaptor protein PTIP, thus inhibiting H3K4 methylation and gene activation	SIGNOR-251712
P09651	Q9UHD9	2	binding	up-regulates quantity by stabilization	0.458	Confirmation of binding of recombinant full-length hnRNPA1 and hnRNPU proteins with ubiquilin-2 by GST-pull-down assays\|Additionally, our evidence that ubiquilin-2 is in- volved in stabilizing hnRNPA1 protein	SIGNOR-262270
Q9UNE7	Q16665	1	ubiquitination	down-regulates quantity by destabilization	0.376	the ubiquitin ligase activity of CHIP regulates HIF-1α degradation.	SIGNOR-271426
O96017	Q9NQS7	1	phosphorylation	up-regulates activity	0.261	Also, inhibition of Chk2 by Chk2 inhibitor II in cytokinesis after release of cells from a nocodazole-induced prometaphase block diminished INCENP localization to the midbody center in late midbodies (Fig. 1, M and N).\|In turn, active Chk2 phosphorylates human INCENP at the newly identified site Ser91 to promote INCENP binding to Mklp2, resulting in recruitment of the INCENP\u2013Mklp2 complex to the midbody center through Mklp2\u2019s interaction with the midbody protein Cep55 to delay abscission.	SIGNOR-279695
P61244	Q9Y6D9	2	binding	up-regulates activity	0.301	the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences.	SIGNOR-240357
P68366	Q14980	2	binding	up-regulates	0.514	Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.	SIGNOR-116788
Q7Z6J0	Q9UQF2	2	binding	up-regulates	0.283	We find that posh and jips directly associate with one another to form a multiprotein complex, pjac (posh-jip apoptotic complex), that includes all of the known kinase components of the pathway. Our observations indicate that this complex is required for jnk activation and cell death in response to apoptotic stimuli.	SIGNOR-145393
P06493	P22674	2	binding	up-regulates activity	0.335	CDK2 is the predominant activating complex form of CCNO, but CCNO can bind to CDK1 to form an activating complex in the absence of CDK2.	SIGNOR-275617
P29317	P52803	2	binding	up-regulates	0.922	Members of the epha subfamily of receptor tyrosine kinases and their ephrin-a ligands have been implicated in the guidance of retinal axons along the anterior-posterior axis of the chick optic tectum.	SIGNOR-52467
Q01105-2	P68400	0	phosphorylation	down-regulates	0.365	Ckii-mediated phosphorylation at ser9 hinders nuclear import of set	SIGNOR-200798
P09471	Q99677	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-257258
P98170	O95831	1	ubiquitination	down-regulates quantity by destabilization	0.434	Notably, cotransfection of XIAP along with AIF resulted in the complete inhibition of DNA degradation (21.2% degraded nuclei), suggesting that XIAP directly abrogates the ability of AIF to induce chromatin degradation.\|XIAP binds and ubiquitinates AIF, and in this study, we determined the functional consequences of XIAP-mediated AIF ubiquitination.	SIGNOR-278537
Q12968	Q08209	0	dephosphorylation	up-regulates	0.538	Calcineurin directly dephosphorylates nfat resulting in the nuclear import of nfat.	SIGNOR-176376
Q99767	P61764	2	binding	up-regulates activity	0.701	Munc18-1 is a neuronal protein that interacts with syntaxin 1 and is required for synaptic vesicle exocytosis. We have now identified two Munc18-1-interacting proteins called Mint1 and Mint2 that may mediate the function of Munc18-1.	SIGNOR-264037
Q7Z570	P58166	1	transcriptional regulation	up-regulates quantity by expression	0.2	ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3).	SIGNOR-269462
P37231	P36507	2	binding	up-regulates	0.2	The genomic activity of ppargamma is modulated, in addition to ligand binding, by phosphorylation of a serine residue by mapks, such as extracellular signal-regulated protein kinases-1/2 (erk-1/2), or by nucleocytoplasmic compartmentalization through the erk activators mapk kinases-1/2 (mek-1/2). These mapks phosphorylate (in humans) ser 84 in the ppargamma1 and ser 114 in ppargamma2 isoform.	SIGNOR-179393
P19086	P32249	2	binding	up-regulates activity	0.249	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-257110
P43489	P23510	2	binding	up-regulates	0.921	Activation of nf-kappab in ox40-transfected hsb-2 cells was detected by electrophoretic mobility shift assay within 30 min after the binding of the ligand gp34.	SIGNOR-54927
Q13177	P35240	1	phosphorylation	down-regulates	0.512	Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth,	SIGNOR-159768
P46527	Q06124	0	dephosphorylation	up-regulates activity	0.281	Moreover, SHP-2 was strongly activated on G-CSF stimulation and specifically dephosphorylated p27(Kip1) in vitro.\|Most importantly, we could illustrate that SHP-2 modulates p27 (Kip1) stability and contributes to p27 (Kip1)-mediated cell cycle progression.	SIGNOR-277168
Q96J02	Q86Y01	1	ubiquitination	down-regulates	0.7	Itch/aip4 mediates deltex degradation through the formation of k29-linked polyubiquitin chains.	SIGNOR-150002
Q16531	Q01094	2	binding	up-regulates	0.351	We show that ddb, a putative dna repair protein, associates with the activation domain of e2f1 / expression of ddb specifically stimulated e2f1-activated transcription	SIGNOR-54096
Q96KS0	P30566	1	hydroxylation	up-regulates activity	0.2	ADSL is hydroxylated by EglN2 on Proline 24. An integrated transcriptomics and metabolomics analysis reveals that ADSL activates the oncogenic cMYC pathway by regulating cMYC protein level via a mechanism requiring ADSL proline 24 hydroxylation. ADSL regulates cMYC protein level through adenosine levels	SIGNOR-266613
P04150	P07900	2	binding	down-regulates	0.735	We report the crucial underlying role of the intranuclear heat shock protein 90 molecular chaperone complex in pulsatile GR regulation. Pharmacological interference of heat shock protein 90 (HSP90) with geldanamycin during the intranuclear chaperone cycle completely ablated GR's cyclical activity, cyclical cAMP response element-binding protein (CREB) binding protein (CBP)/p300 recruitment, and the associated cyclical acetylation at the promoter region.	SIGNOR-251667
Q13153	Q70Z35	1	phosphorylation	down-regulates activity	0.367	P21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase. PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ.	SIGNOR-277181
Q00535	O14936	1	phosphorylation	up-regulates activity	0.288	Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK.\|We found that Cdk5 phosphorylates and regulates CASK distribution to membranes.	SIGNOR-280216
Q99720	Q9NZQ7	1	stabilization	up-regulates quantity by stabilization	0.2	We propose that Sigma1 is a ligand-operated scaffolding protein that promotes the stability, processing, assembly, and trafficking of specific proteins in the secretory pathway of cancer cells. In support of this hypothesis, we found that siRNA-mediated knockdown of Sigma1 resulted in a significant decrease in PD-L1 protein levels in triple-negative MDA-MB-231 breast cancer and androgen-independent PC3 prostate cancer cells	SIGNOR-274974
O95433	P07900	2	binding	up-regulates activity	0.742	The N-terminal region of Aha1 interacts with the central domain of Hsp90 and stimulates Hsp90 ATPase activity	SIGNOR-252211
P08238	P31948	2	binding	down-regulates activity	0.855	Hsp90 chaperone cycle is tightly regulated by another group of proteins referred to as ‘co-chaperones'. Their stability does not depend on Hsp90 function but they interact with distinct Hsp90 conformational states, providing directionality to the Hsp90 cycle4. Furthermore, certain co-chaperones, such as HOP and Cdc37p50 inhibit the Hsp90 chaperone cycle, assisting in delivery of distinct sets of client proteins (steroid hormone receptors and kinases, respectively) to the Hsp90 chaperone machine.	SIGNOR-261412
Q96NY9	P68400	0	phosphorylation	up-regulates activity	0.2	Here, we show that the CK2 kinase phosphorylates MUS81 at Serine 87 in late-G2/mitosis, and upon mild replication stress. Phosphorylated MUS81 interacts with SLX4, and this association promotes the function of the MUS81 complex.	SIGNOR-273626
Q8IXJ9	P42772	1	transcriptional regulation	up-regulates quantity by expression	0.276	Tumor suppressor ASXL1 is essential for the activation of INK4B expression in response to oncogene activity and anti-proliferative signals	SIGNOR-241759
Q92915	P67870	0	phosphorylation	up-regulates activity	0.27	Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents.	SIGNOR-275745
P30556	P50148	2	binding	up-regulates activity	0.643	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-257017
P10912	O60674	0	phosphorylation	up-regulates activity	0.766	Jak2 is then phosphorylated and, in turn, phosphorylates the GHR and the signal transducers and activators of transcription (STAT) protein.	SIGNOR-279198
O43292	Q96S52	2	binding	up-regulates activity	0.895	To determine roles for PIG-S and PIG-T, we disrupted these genes in mouse F9 cells by homologous recombination. PIG-S and PIG-T knockout cells were defective in transfer of GPI to proteins, particularly in formation of the carbonyl intermediates. We also demonstrate that PIG-S and PIG-T form a protein complex with GAA1 and GPI8, and that PIG-T maintains the complex by stabilizing the expression of GAA1 and GPI8.	SIGNOR-261361
Q15831	P06241	0	phosphorylation	down-regulates activity	0.327	Moreover, Fyn kinase directly phosphorylated LKB1 on tyrosine 261 and 365 residues and mutations of these sites resulted in LKB1 export into the cytoplasm and increased AMPK phosphorylation.	SIGNOR-278477
Q96QT4	P16885	1	phosphorylation	up-regulates activity	0.263	We present data indicating that TRPM7 phosphorylates phospholipase C\u03b32 at position Ser1164 in the C2-domain, and at position Thr1045 in the linker between the catalytic region and the C2 domain.	SIGNOR-278460
P06493	Q8TD19	1	phosphorylation	up-regulates activity	0.482	We now identify Plk1 as Nek9 direct activator and propose a two-step activation mechanism that involves Nek9 sequential phosphorylation by CDK1 and Plk1. while CDK1 activity is necessary for Nek9 phosphorylation in mitosis and the resulting change in electrophoretical mobility, Nek9 Thr210 phosphorylation and mitotic activation requires both CDK1 and Plk1.	SIGNOR-273889
Q14686	P28482	0	phosphorylation	up-regulates activity	0.2	In vitro phosphorylation studies with His-tagged TRBP (795–931) suggested that S884 can be phosphorylated by MAPK (ERK2) in vitro (Fig. 10A).Analysis of in vitro and in vivo receptor interactions with TRBP suggested that S884 allowed selective interactions for ERβ, TR, and RXR vs. ERα.	SIGNOR-265882
Q07955	P51955	0	phosphorylation	down-regulates activity	0.385	First, NEK2 interacts with and phosphorylates SRSF1.	SIGNOR-279344
Q14232	P49841	2	binding	down-regulates	0.2	Akt also promotes protein synthesis by phosphorylating and inactivating gsk3b, thus releasing the gsk3b-dependent inhibition of the eukariotic translation initiation factor 2b (eif2b).	SIGNOR-175436
Q92830	Q5TEC6	1	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-269599
Q08211	P35637	0	relocalization	down-regulates activity	0.482	We found that ALS mutants of FUS co-localized with Caprin-1, DDX3X, and DHX9 in cytoplasmic inclusions that could lead to the mis-regulation of their respective pathways, providing further clues to the mechanism of ALS pathogenesis.\|FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. \| We also demonstrated the co-localization of DHX9, DDX3X and Caprin-1 with cytoplasmic EGFP-P525L mutant FUS inclusions in primary cortical neurons	SIGNOR-262810
P31645	Q9UHD2	0	phosphorylation	up-regulates activity	0.2	Taken together, our data suggest that TBK1 expression promotes the general cellular clearance mechanism of soluble HTT and prevents its accumulation and aggregation by enhancing autophagy.\|This confirmed that TBK1 phosphorylated endogenous HTT at S13 (Fig XREF_FIG G and H).	SIGNOR-278384
Q99527	P59768	2	binding	up-regulates activity	0.385	GPCRs transduce their signal via G-protein heterotrimers (αβγ) that dissociate in free Gα-subunit protein and Gβγ-subunit protein complexes following ligand stimulation; GNG2 stands for the subunit γ, which dissociates from the receptor after the binding of GTP on α-subunit.	SIGNOR-251104
Q13153	O15344	1	phosphorylation	up-regulates activity	0.2	Pak1 phosphorylates the N-terminus of Mid1 to promote its association with cortical nodes.\|Pak1 promotes Mid1 localization to cortical nodes.	SIGNOR-279307
Q8IZF0	Q8N2C7	2	binding	up-regulates activity	0.809	The NALCN complex in the brain consists of NALCN, UNC80 and UNC79. UNC80 directly associates with NALCN and UNC79 forms part of the complex by its interaction with UNC80.	SIGNOR-265184
P14384	P69905	1	cleavage	down-regulates activity	0.2	Both human plasma carboxypeptidase N (CPN) and membrane-bound carboxypeptidase M (CPM) released the C-terminal arginine (alpha-Arg141) of the alpha chain of human adult hemoglobin. Thus, the hydrolysis of hemoglobin by CPM and CPN demonstrated the contribution of the alpha-Arg141 residue to sustaining the tetrameric structure of hemoglobin and its normal oxygen affinity and vasoactivity.	SIGNOR-256507

P63096

P25101

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-257052

P50539

P61244

2

binding

up-regulates activity

0.558

The role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences.

SIGNOR-240314

Q969Q1

P55036

1

polyubiquitination

down-regulates quantity by destabilization

0.403

S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s. Surprisingly, the same four Lys residues on S5a, Lys-74, Lys-122, Lys-262, and Lys-365 were ubiquitinated by MuRF1 and E6AP (Fig. 10).

SIGNOR-272741

Q14689

Q12841

2

binding

up-regulates activity

0.48

We identified DIP2A as a novel FSTL1-binding partner from the membrane fraction of endothelial cells. Co-immunoprecipitation assays revealed a direct physical interaction between FSTL1 and DIP2A. The work in the current study identifies DIP2A as a novel receptor for FSTL1 that mediates Akt activation and cell survival and function in cardiovascular cells in vitro.

SIGNOR-266603

P46108

P09619

2

binding

up-regulates

0.609

Crk could bind to both pdgf alpha- and beta-receptors in vivo

SIGNOR-75884

P25105

P63092

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 ‚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-256789

P53367

Q15139

0

phosphorylation

up-regulates

0.385

We report that arfaptins contain an amphipathic helix (ah) preceding the bar domain, which is essential for their binding to phosphatidylinositol 4-phosphate (pi(4)p)-containing liposomes and the tgn of mammalian cells. The binding of arfaptin1, but not arfaptin2, to pi(4)p is regulated by protein kinase d (pkd) mediated phosphorylation at ser100 within the ah. We also found that only arfaptin1 is required for the pkd-dependent trafficking of chromogranin a by the regulated secretory pathway.

SIGNOR-202101

O60216

Q8N3U4

2

binding

up-regulates quantity by stabilization

0.965

Cohesin is an evolutionarily conserved complex composed of four core proteins (SMC1A, SMC3, RAD21 and either STAG2 or STAG1) that form a ring-shaped structure able to encircle chromatin

SIGNOR-261511

Q06413

P35580

1

transcriptional regulation

up-regulates quantity by expression

0.345

Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation

SIGNOR-238769

O75293

Q9UQ88

2

binding

down-regulates activity

0.2

Western blot analysis for SPDEF revealed that overexpression of GADD45α, β and γ prevents SPDEF degradation mediated by CDK11p58 |We identified CDK11p58 as an interaction partner of GADD45α by co-immunoprecipitation analysis. We corroborated these data by co-immunoprecipitation in vitro translation assays, showing that all three members of the GADD45 family interact with CDK11p58.

SIGNOR-273024

P19525

P06493

1

phosphorylation

down-regulates

0.328

Our findings demonstrate that (i) pkr, ser/thr kinase, phosphorylates its new substrate cdc2 at the tyr 4 residue, (ii) pkr-mediated tyr 4-phosphorylation facilitates cdc2 ubiquitination and proteosomal degradation

SIGNOR-164809

P46934

Q13501

1

ubiquitination

down-regulates quantity by destabilization

0.277

Depletion of NEDD4 dramatically reduced the LC3 protein level and elevated the SQSTM1 protein level.|Furthermore, SQSTM1 is ubiquitinated by NEDD4 while LC3 functions as an activator of NEDD4 ligase activity.

SIGNOR-278637

P48729

Q2M2I3

2

binding

up-regulates quantity

0.2

We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.

SIGNOR-273750

Q16539

P41970

1

phosphorylation

up-regulates

0.379

Tcf sap-1a is efficiently phosphorylated by p38 map kinase in vitro and in vivo on the homologous residues ser381 and ser387. Mutation of these sites to alanine severely reduces c-fos sre-dependent transcription mediated by sap-1a and p38 map kinase.

SIGNOR-47685

Q86TM6

P60484

1

ubiquitination

down-regulates quantity by destabilization

0.2

Secondly, HRD1 promotes PTEN ubiquitination and degradation.

SIGNOR-278724

O00506

P46937

1

phosphorylation

up-regulates activity

0.265

Collectively, our data demonstrate that loss of STK25 promotes YAP/TAZ activation.|Lastly, we assessed if STK25 is able to promote YAP phosphorylation in the absence of LATS-HM phosphorylation, based on our in vitro kinase assay results.

SIGNOR-278993

Q01860

Q6U7Q0

0

transcriptional regulation

up-regulates quantity by expression

0.2

Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays revealed that Zfp322a binds to Pou5f1 and Nanog promoters and regulates their transcription.

SIGNOR-264900

P10915

P14780

0

cleavage

down-regulates quantity by destabilization

0.341

Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix.

SIGNOR-256328

P31749

P12931

0

phosphorylation

up-regulates activity

0.677

Regulation of Akt/PKB Activation by Tyrosine PhosphorylationAs shown in Fig. 2 d, while mutation of Tyr340 has little effect on either tyrosine phosphorylation or kinase activity of Akt induced by Src527F, substitution of Tyr315 or Tyr326 with a phenylalanine, respectively, dramatically reduces both the tyrosine phosphorylation and kinase activity of Akt. The combination of these two mutations abolishes Src-induced tyrosine phosphorylation of Akt as well as its kinase activity.

SIGNOR-252623

O14920

P54646

0

phosphorylation

up-regulates

0.257

These results demonstrate that the ikk is a direct substrate of ampk_2 and that its phosphorylation on ser177 and ser181no initiates the activation of the ampk_2 in endothelial cells which in turn phosphorylates and activates the _-subunit of the ikk. The latter also induces a higher rate of ikk auto-inactivation and thus attenuates the activation of nf_b and the expression of inflammatory genes

SIGNOR-174405

O15105

Q9Y5K5

2

binding

up-regulates

0.662

Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases.

SIGNOR-138879

P0DPK2

Q92830

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-269597

Q12809

Q15139

0

phosphorylation

down-regulates activity

0.2

Based on LC-MS results from in vivo and HEK293 cell experiments we chose four KV11.1 mutant candidates for further functional analysis. Ablation of the putative PKD phosphorylation site in the mutant S284A increased the maximal current indicating S284 as a main PKD target in KV11.1.

SIGNOR-277612

P32519

P67775

0

dephosphorylation

down-regulates activity

0.2

Elf-1 enhances the expression of CD3zeta, whereas it suppresses the expression of FcRgamma gene and lupus T cells have decreased amounts of DNA-binding 98 kDa form of Elf-1. We show that the aberrantly increased PP2A in lupus T cells dephosphorylates Elf-1 at Thr-231. Dephosphorylation results in limited expression and binding of the 98 kDa Elf-1 form to the CD3zeta and FcRgamma promoters. Suppression of the expression of the PP2A leads to increased expression of CD3zeta and decreased expression of FcRgamma genes and correction of the early signaling response

SIGNOR-248634

Q9C0F0

O60341

2

binding

down-regulates activity

0.266

Here, we showed that ASXL3 interacts with HP1α and LSD1, leading to transcriptional repression.

SIGNOR-266764

O75143

Q8TDY2

2

binding

up-regulates

0.919

Atg13 directly binds fip200.

SIGNOR-184120

P35568

Q04759

0

phosphorylation

down-regulates activity

0.567

Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101).

SIGNOR-260906

P21246

Q9UM73

2

binding

up-regulates

0.547

We conclude from this series of experiments that ptn specifically binds to the alk orphan receptor as a high affinity ligand at least in part via the putative ligand binding domain described above.

SIGNOR-106411

P05154

P02751

2

binding

down-regulates activity

0.312

SERPINA5 inhibits HCC cell migration by directly interacting with fibronectin. SERPINA5 disrupts the fibronectin–integrin β1 signaling pathway.

SIGNOR-265881

P12931

P35916

1

phosphorylation

up-regulates

0.513

Vegfr-3 is a direct c-src target and mass spectrometry analysis identified the sites phosphorylated by c-src as tyrosine 830, 833, 853, 1063, 1333, and 1337 vegfr-3 phosphorylation activates the recruitment to the receptor of the adaptor proteins crki/ii and shc inducing activation of jnk.

SIGNOR-165035

P49336

P84022

1

phosphorylation

down-regulates

0.566

Similarly, tgf-?-Induced and cdk8/9-mediated phosphorylation of smad3 at threonine 179 (t179) is important for binding of the nedd4l e3 ubiquitin ligase, which accelerates smad3 turnover;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3.

SIGNOR-161557

Q15418

P28482

0

phosphorylation

up-regulates activity

0.759

Several lines of evidence indicate that the mapkap-k1 isoforms are also activated by mapks in vivo via the ras-dependent protein kinase cascade that is triggered by growth factors or tumor-promoting phorbol esters, such as phorbol 12-myristate 13-acetate (pma). here we identify six sites in mapkap-k1a that become phosphorylated in transfected cos-1 cells. The inactive form of mapkap-k1a in unstimulated cells is partially phosphorylated at ser222 and ser733. Stimulation with phorbol 12-myristate 13-acetate induces the phosphorylation of thr360, ser364, thr574, and ser381 and increases the phosphorylation of ser222 and ser733.

SIGNOR-219308

P30307

P06493

2

dephosphorylation

up-regulates

0.858

Cdk1/cdc2 activation involves tyr15/thr14 dephosphorylation by cdc25c

SIGNOR-186621

P31749

Q9Y4P1

1

phosphorylation

up-regulates activity

0.31

In this study, we identified a novel phosphorylation site at Ser34 of ATG4B induced by AKT in HCC cells.| In brief, our results demonstrate for the first time that the phosphorylation of ATG4B at Ser34 participates in the metabolic reprogramming of HCC cells via repressing mitochondrial function, which possibly results from the Ser34 phosphorylation-induced mitochondrial enrichment of ATG4B and the subsequent inhibition of F1Fo-ATP synthase activity.

SIGNOR-275834

Q06413

Q9UKV0

2

binding

down-regulates

0.633

Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent manner

SIGNOR-235642

P02545

Q9UH99

1

relocalization

up-regulates activity

0.622

In the case of Sun2, there is some evidence that A-type lamins might contribute to Sun2 localization in the INM. We report that an interaction between subunits of the HOPS complex and the ERM (ezrin, radixin, moesin) proteins is required for the delivery of EGF receptor (EGFR) to lysosomes. Inhibiting either ERM proteins or the HOPS complex leads to the accumulation of the EGFR into early endosomes, delaying its degradation.

SIGNOR-261310

Q14833

P63092

2

binding

up-regulates activity

0.344

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-264082

Q96J02

Q12778

1

ubiquitination

down-regulates quantity by destabilization

0.258

Mechanistically, Itch ubiquitinates Foxo1 for proteasomal degradation.

SIGNOR-278698

P63000

Q8N103

0

gtpase-activating protein

down-regulates activity

0.402

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

SIGNOR-260524

Q92598

P19784

0

phosphorylation

down-regulates activity

0.327

Protein kinase CK2 phosphorylates Hsp105 alpha at Ser509 and modulates its function. | the phosphorylation of Hsp105 alpha at Ser(509) abolished the inhibitory activity of Hsp105 alpha in vitro.

SIGNOR-251008

P67775

P23443

1

dephosphorylation

down-regulates

0.72

Protein phosphatase 2a inactivates the mitogen-stimulated s6 kinase from swiss mouse 3t3 cells

SIGNOR-23575

P04637

Q9HCI7

0

ubiquitination

down-regulates activity

0.37

Here we describe MSL2, a novel E3 ligase for p53 that promotes ubiquitin-dependent cytoplasmic p53 localization. Unlike Mdm2 or most other p53 E3 ligases, MSL2-mediated p53 ubiquitination does not affect the stability of p53. Moreover, the MSL2-mediated effect on p53 is Mdm2-independent. Thus, our study identifies an important ubiquitin-ligase for modulating p53 subcellular localization. MSL2 ubiquitination of p53 is required for p53 cytoplasmic localization.

SIGNOR-271774

Q02156

P11362

1

phosphorylation

up-regulates

0.2

Phosphorylation of serine 779 in fibroblast growth factor receptor 1 and 2 by protein kinase c(epsilon) regulates ras/mitogen-activated protein kinase signaling and neuronal differentiationour findings show that in addition to fgfr tyrosine phosphorylation, the phosphorylation of a conserved serine residue, ser(779), can quantitatively control ras/mapk signaling to promote specific cellular responses.

SIGNOR-201671

Q9NYJ8

Q9Y4K3

2

binding

up-regulates activity

0.933

The irak1/traf6 complex can also activate jnk and p38 signalling through assembly of a catalytically active tab2-tab3-tak1 complex.

SIGNOR-205458

P42261

Q13555

0

phosphorylation

up-regulates activity

0.63

In this study, CaM-kinase II enhanced kainate currents of expressed glutamate receptor 6 in 293 cells and of wild-type glutamate receptor 1, but not the Ser-627 to Ala mutant, in Xenopus oocytes. | This CaM-kinase II regulatory phosphorylation site is conserved in all AMPA/kainate-type glutamate receptors, and its phosphorylation may be important in enhancing postsynaptic responsiveness as occurs during synaptic plasticity.

SIGNOR-250697

P31314

P06400

2

binding

down-regulates activity

0.2

ectopic HOX11 expression resulted in hyperphosphorylation of the retinoblastoma protein (Rb), which correlated with inhibition of the major Rb serine/threonine phosphatase PP1.

SIGNOR-240725

Q13950

P84022

2

binding

down-regulates activity

0.738

Tgf-beta inhibited the expression of the cbfa1 and osteocalcin genes, whose expression is controlled by cbfa1 in osteoblast-like cell lines. This inhibition was mediated by smad3, which interacts physically with cbfa1 and represses its transcriptional activity at the cbfa1-binding ose2 promoter sequence.

SIGNOR-235902

Q06210

P17252

0

phosphorylation

down-regulates activity

0.307

Phosphorylation of human glutamine:fructose-6-phosphate amidotransferase by cAMP-dependent protein kinase at serine 205 blocks the enzyme activity.

SIGNOR-249040

Q6IQ49

Q9NZJ0

2

binding

down-regulates quantity by destabilization

0.282

Here, we identify human SDE2 as a new genome surveillance factor regulated by PCNA interaction. The cleaved SDE2 products need to be degraded by the CRL4CDT2 ubiquitin E3 ligase in a cell cycle- and DNA damage-dependent manner, and failure to degrade SDE2 impairs S phase progression and cellular survival.

SIGNOR-272807

Q9NY46

Q92914

2

binding

down-regulates activity

0.2

Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.

SIGNOR-253446

P27695

Q00987

0

ubiquitination

down-regulates quantity by destabilization

0.416

Once the reaction proceeds beyond the monoubiquitination stage, MDM2 polyubiquitinates APE1 for degradation.

SIGNOR-278555

Q9UL17

P60568

1

transcriptional regulation

down-regulates quantity by repression

0.473

T-bet Transactivates the IFNγ Gene and Represses the IL-2 Gene in EL4 Cells

SIGNOR-266233

Q02962

O75688

0

dephosphorylation

down-regulates activity

0.2

PPM1B can dephosphorylate the Pax2 activation domain and displace the adaptor protein PTIP, thus inhibiting H3K4 methylation and gene activation

SIGNOR-251712

P09651

Q9UHD9

2

binding

up-regulates quantity by stabilization

0.458

Confirmation of binding of recombinant full-length hnRNPA1 and hnRNPU proteins with ubiquilin-2 by GST-pull-down assays|Additionally, our evidence that ubiquilin-2 is in- volved in stabilizing hnRNPA1 protein

SIGNOR-262270

Q9UNE7

Q16665

1

ubiquitination

down-regulates quantity by destabilization

0.376

the ubiquitin ligase activity of CHIP regulates HIF-1α degradation.

SIGNOR-271426

O96017

Q9NQS7

1

phosphorylation

up-regulates activity

0.261

Also, inhibition of Chk2 by Chk2 inhibitor II in cytokinesis after release of cells from a nocodazole-induced prometaphase block diminished INCENP localization to the midbody center in late midbodies (Fig. 1, M and N).|In turn, active Chk2 phosphorylates human INCENP at the newly identified site Ser91 to promote INCENP binding to Mklp2, resulting in recruitment of the INCENP\u2013Mklp2 complex to the midbody center through Mklp2\u2019s interaction with the midbody protein Cep55 to delay abscission.

SIGNOR-279695

P61244

Q9Y6D9

2

binding

up-regulates activity

0.301

the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences.

SIGNOR-240357

P68366

Q14980

2

binding

up-regulates

0.514

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

SIGNOR-116788

Q7Z6J0

Q9UQF2

2

binding

up-regulates

0.283

We find that posh and jips directly associate with one another to form a multiprotein complex, pjac (posh-jip apoptotic complex), that includes all of the known kinase components of the pathway. Our observations indicate that this complex is required for jnk activation and cell death in response to apoptotic stimuli.

SIGNOR-145393

P06493

P22674

2

binding

up-regulates activity

0.335

CDK2 is the predominant activating complex form of CCNO, but CCNO can bind to CDK1 to form an activating complex in the absence of CDK2.

SIGNOR-275617

P29317

P52803

2

binding

up-regulates

0.922

Members of the epha subfamily of receptor tyrosine kinases and their ephrin-a ligands have been implicated in the guidance of retinal axons along the anterior-posterior axis of the chick optic tectum.

SIGNOR-52467

Q01105-2

P68400

0

phosphorylation

down-regulates

0.365

Ckii-mediated phosphorylation at ser9 hinders nuclear import of set

SIGNOR-200798

P09471

Q99677

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-257258

P98170

O95831

1

ubiquitination

down-regulates quantity by destabilization

0.434

Notably, cotransfection of XIAP along with AIF resulted in the complete inhibition of DNA degradation (21.2% degraded nuclei), suggesting that XIAP directly abrogates the ability of AIF to induce chromatin degradation.|XIAP binds and ubiquitinates AIF, and in this study, we determined the functional consequences of XIAP-mediated AIF ubiquitination.

SIGNOR-278537

Q12968

Q08209

0

dephosphorylation

up-regulates

0.538

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

SIGNOR-176376

Q99767

P61764

2

binding

up-regulates activity

0.701

Munc18-1 is a neuronal protein that interacts with syntaxin 1 and is required for synaptic vesicle exocytosis. We have now identified two Munc18-1-interacting proteins called Mint1 and Mint2 that may mediate the function of Munc18-1.

SIGNOR-264037

Q7Z570

P58166

1

transcriptional regulation

up-regulates quantity by expression

0.2

ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3).

SIGNOR-269462

P37231

P36507

2

binding

up-regulates

0.2

The genomic activity of ppargamma is modulated, in addition to ligand binding, by phosphorylation of a serine residue by mapks, such as extracellular signal-regulated protein kinases-1/2 (erk-1/2), or by nucleocytoplasmic compartmentalization through the erk activators mapk kinases-1/2 (mek-1/2). These mapks phosphorylate (in humans) ser 84 in the ppargamma1 and ser 114 in ppargamma2 isoform.

SIGNOR-179393

P19086

P32249

2

binding

up-regulates activity

0.249

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-257110

P43489

P23510

2

binding

up-regulates

0.921

Activation of nf-kappab in ox40-transfected hsb-2 cells was detected by electrophoretic mobility shift assay within 30 min after the binding of the ligand gp34.

SIGNOR-54927

Q13177

P35240

1

phosphorylation

down-regulates

0.512

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

SIGNOR-159768

P46527

Q06124

0

dephosphorylation

up-regulates activity

0.281

Moreover, SHP-2 was strongly activated on G-CSF stimulation and specifically dephosphorylated p27(Kip1) in vitro.|Most importantly, we could illustrate that SHP-2 modulates p27 (Kip1) stability and contributes to p27 (Kip1)-mediated cell cycle progression.

SIGNOR-277168

Q96J02

Q86Y01

1

ubiquitination

down-regulates

0.7

Itch/aip4 mediates deltex degradation through the formation of k29-linked polyubiquitin chains.

SIGNOR-150002

Q16531

Q01094

2

binding

up-regulates

0.351

We show that ddb, a putative dna repair protein, associates with the activation domain of e2f1 / expression of ddb specifically stimulated e2f1-activated transcription

SIGNOR-54096

Q96KS0

P30566

1

hydroxylation

up-regulates activity

0.2

ADSL is hydroxylated by EglN2 on Proline 24. An integrated transcriptomics and metabolomics analysis reveals that ADSL activates the oncogenic cMYC pathway by regulating cMYC protein level via a mechanism requiring ADSL proline 24 hydroxylation. ADSL regulates cMYC protein level through adenosine levels

SIGNOR-266613

P04150

P07900

2

binding

down-regulates

0.735

We report the crucial underlying role of the intranuclear heat shock protein 90 molecular chaperone complex in pulsatile GR regulation. Pharmacological interference of heat shock protein 90 (HSP90) with geldanamycin during the intranuclear chaperone cycle completely ablated GR's cyclical activity, cyclical cAMP response element-binding protein (CREB) binding protein (CBP)/p300 recruitment, and the associated cyclical acetylation at the promoter region.

SIGNOR-251667

Q13153

Q70Z35

1

phosphorylation

down-regulates activity

0.367

P21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase. PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ.

SIGNOR-277181

Q00535

O14936

1

phosphorylation

up-regulates activity

0.288

Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK.|We found that Cdk5 phosphorylates and regulates CASK distribution to membranes.

SIGNOR-280216

Q99720

Q9NZQ7

1

stabilization

up-regulates quantity by stabilization

0.2

We propose that Sigma1 is a ligand-operated scaffolding protein that promotes the stability, processing, assembly, and trafficking of specific proteins in the secretory pathway of cancer cells. In support of this hypothesis, we found that siRNA-mediated knockdown of Sigma1 resulted in a significant decrease in PD-L1 protein levels in triple-negative MDA-MB-231 breast cancer and androgen-independent PC3 prostate cancer cells

SIGNOR-274974

O95433

P07900

2

binding

up-regulates activity

0.742

The N-terminal region of Aha1 interacts with the central domain of Hsp90 and stimulates Hsp90 ATPase activity

SIGNOR-252211

P08238

P31948

2

binding

down-regulates activity

0.855

Hsp90 chaperone cycle is tightly regulated by another group of proteins referred to as ‘co-chaperones'. Their stability does not depend on Hsp90 function but they interact with distinct Hsp90 conformational states, providing directionality to the Hsp90 cycle4. Furthermore, certain co-chaperones, such as HOP and Cdc37p50 inhibit the Hsp90 chaperone cycle, assisting in delivery of distinct sets of client proteins (steroid hormone receptors and kinases, respectively) to the Hsp90 chaperone machine.

SIGNOR-261412

Q96NY9

P68400

0

phosphorylation

up-regulates activity

0.2

Here, we show that the CK2 kinase phosphorylates MUS81 at Serine 87 in late-G2/mitosis, and upon mild replication stress. Phosphorylated MUS81 interacts with SLX4, and this association promotes the function of the MUS81 complex.

SIGNOR-273626

Q8IXJ9

P42772

1

transcriptional regulation

up-regulates quantity by expression

0.276

Tumor suppressor ASXL1 is essential for the activation of INK4B expression in response to oncogene activity and anti-proliferative signals

SIGNOR-241759

Q92915

P67870

0

phosphorylation

up-regulates activity

0.27

Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents.

SIGNOR-275745

P30556

P50148

2

binding

up-regulates activity

0.643

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-257017

P10912

O60674

0

phosphorylation

up-regulates activity

0.766

Jak2 is then phosphorylated and, in turn, phosphorylates the GHR and the signal transducers and activators of transcription (STAT) protein.

SIGNOR-279198

O43292

Q96S52

2

binding

up-regulates activity

0.895

To determine roles for PIG-S and PIG-T, we disrupted these genes in mouse F9 cells by homologous recombination. PIG-S and PIG-T knockout cells were defective in transfer of GPI to proteins, particularly in formation of the carbonyl intermediates. We also demonstrate that PIG-S and PIG-T form a protein complex with GAA1 and GPI8, and that PIG-T maintains the complex by stabilizing the expression of GAA1 and GPI8.

SIGNOR-261361

Q15831

P06241

0

phosphorylation

down-regulates activity

0.327

Moreover, Fyn kinase directly phosphorylated LKB1 on tyrosine 261 and 365 residues and mutations of these sites resulted in LKB1 export into the cytoplasm and increased AMPK phosphorylation.

SIGNOR-278477

Q96QT4

P16885

1

phosphorylation

up-regulates activity

0.263

We present data indicating that TRPM7 phosphorylates phospholipase C\u03b32 at position Ser1164 in the C2-domain, and at position Thr1045 in the linker between the catalytic region and the C2 domain.

SIGNOR-278460

P06493

Q8TD19

1

phosphorylation

up-regulates activity

0.482

We now identify Plk1 as Nek9 direct activator and propose a two-step activation mechanism that involves Nek9 sequential phosphorylation by CDK1 and Plk1. while CDK1 activity is necessary for Nek9 phosphorylation in mitosis and the resulting change in electrophoretical mobility, Nek9 Thr210 phosphorylation and mitotic activation requires both CDK1 and Plk1.

SIGNOR-273889

Q14686

P28482

0

phosphorylation

up-regulates activity

0.2

In vitro phosphorylation studies with His-tagged TRBP (795–931) suggested that S884 can be phosphorylated by MAPK (ERK2) in vitro (Fig. 10A).Analysis of in vitro and in vivo receptor interactions with TRBP suggested that S884 allowed selective interactions for ERβ, TR, and RXR vs. ERα.

SIGNOR-265882

Q07955

P51955

0

phosphorylation

down-regulates activity

0.385

First, NEK2 interacts with and phosphorylates SRSF1.

SIGNOR-279344

Q14232

P49841

2

binding

down-regulates

0.2

Akt also promotes protein synthesis by phosphorylating and inactivating gsk3b, thus releasing the gsk3b-dependent inhibition of the eukariotic translation initiation factor 2b (eif2b).

SIGNOR-175436

Q92830

Q5TEC6

1

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-269599

Q08211

P35637

0

relocalization

down-regulates activity

0.482

We found that ALS mutants of FUS co-localized with Caprin-1, DDX3X, and DHX9 in cytoplasmic inclusions that could lead to the mis-regulation of their respective pathways, providing further clues to the mechanism of ALS pathogenesis.|FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. | We also demonstrated the co-localization of DHX9, DDX3X and Caprin-1 with cytoplasmic EGFP-P525L mutant FUS inclusions in primary cortical neurons

SIGNOR-262810

P31645

Q9UHD2

0

phosphorylation

up-regulates activity

0.2

Taken together, our data suggest that TBK1 expression promotes the general cellular clearance mechanism of soluble HTT and prevents its accumulation and aggregation by enhancing autophagy.|This confirmed that TBK1 phosphorylated endogenous HTT at S13 (Fig XREF_FIG G and H).

SIGNOR-278384

Q99527

P59768

2

binding

up-regulates activity

0.385

GPCRs transduce their signal via G-protein heterotrimers (αβγ) that dissociate in free Gα-subunit protein and Gβγ-subunit protein complexes following ligand stimulation; GNG2 stands for the subunit γ, which dissociates from the receptor after the binding of GTP on α-subunit.

SIGNOR-251104

Q13153

O15344

1

phosphorylation

up-regulates activity

0.2

Pak1 phosphorylates the N-terminus of Mid1 to promote its association with cortical nodes.|Pak1 promotes Mid1 localization to cortical nodes.

SIGNOR-279307

Q8IZF0

Q8N2C7

2

binding

up-regulates activity

0.809

The NALCN complex in the brain consists of NALCN, UNC80 and UNC79. UNC80 directly associates with NALCN and UNC79 forms part of the complex by its interaction with UNC80.

SIGNOR-265184

P14384

P69905

1

cleavage

down-regulates activity

0.2

Both human plasma carboxypeptidase N (CPN) and membrane-bound carboxypeptidase M (CPM) released the C-terminal arginine (alpha-Arg141) of the alpha chain of human adult hemoglobin. Thus, the hydrolysis of hemoglobin by CPM and CPN demonstrated the contribution of the alpha-Arg141 residue to sustaining the tetrameric structure of hemoglobin and its normal oxygen affinity and vasoactivity.

SIGNOR-256507