GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q13285	Q9HAZ1	phosphorylation	up-regulates activity	0.2	Immunoblotting analyses showed that the phosphorylation status of NR5A1 at Ser203 was attenuated by the CLK1/4 inhibitor.	SIGNOR-274117
Q8TD43	P17252	phosphorylation	up-regulates	0.2	Phorbol ester-induced activation of protein kinase c (pkc) increased the ca(2+) sensitivity of wild-type trpm4 but not of two mutants mutated at putative pkc phosphorylation sites.	SIGNOR-132243
Q9P212	Q9UBI6	binding	up-regulates	0.2	In the non-canonical wntpathway, frizzled uses galfaq or galfai and gbetagamma dimers to activate phospholipase c (plc), resulting in protein kinase c (pkc) activation and calcium mobilization that regulates the transcription factor nfat, and frizzled also signals through the small gtpases rho and rac to c-jun n-terminal kinase (jnk), which activates the ap1 transcription factor	SIGNOR-152612
Q9P2J5	Q5S007	phosphorylation	down-regulates activity	0.2	In this study, we elucidated that leucyl-tRNA synthetase (LRS) was an LRRK2 kinase substrate and identified T293 as an LRRK2 phosphorylation site. LRRK2-meidated LRS phosphorylation or G2019S can lead to impairment of LRS editing, increased ER stress, and accumulation of autophagy markers.	SIGNOR-277417
O15269	P00519	phosphorylation	down-regulates	0.2	We demonstrated that the er-resident human protein serine palmitoyltransferase long chain-1 (sptlc1), which is the first enzyme of sphingolipid biosynthesis, is phosphorylated at tyr(164) by the tyrosine kinase abl. this occurred through the specific abl-mediated phosphorylation of sptlc1 on tyr164, leading to the attenuation of its activity.	SIGNOR-202003
Q03113	Q9Y653	binding	up-regulates activity	0.2	Binding of collagen III to ADGRG1 provides a canonical example of adhesion GPCR interactions with ECM proteins (Luo et al., 2011). Identified by an in vitro biotinylation/proteomics approach, extracellular interactions with collagen III were subsequently proven capable of activating ADGRG1-mediated signaling via Gα12/13 followed by RhoA activation to regulate corticogenesis	SIGNOR-272344
P68431	Q9UIF8	binding	down-regulates activity	0.2	The BAZ2B bromodomain has been shown to bind to acetylated H3K14 (H3K14ac), whose presence at promoter regions is generally associated with gene activation. This suggests a potential role for BAZ2B in transcriptional activation.	SIGNOR-266622
P19367	Q8IYT8	phosphorylation	up-regulates activity	0.2	Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).	SIGNOR-274042
P53004	Q05655	phosphorylation	up-regulates activity	0.2	LC-MS/MS analysis of PKCdelta-activated intact hBVR identified phosphorylated serine positions 21, 33, 230, and 237, corresponding to the hBVR Src homology-2 domain motif (Ser(230) and Ser(237)), flanking the ATP-binding motif (Ser(21)) and in PHPS sequence (Ser(33)) as targets of PKCdelta. \|PKCdelta potentiated hBVR reductase activity and accelerated the rate of bilirubin formation.	SIGNOR-275525
O60216	Q9Y6M0	cleavage	up-regulates	0.2	Rad21 is a component of the cohesin complex that holds sister chromatids together during mitosis and repairs double-strand dna breaks. Interestingly, rad21 is cleaved by a caspase-like esp1/separase at the onset of anaphase to trigger sister chromatid separation.	SIGNOR-115426
Q9UKV8	P18031	dephosphorylation	down-regulates activity	0.2	Taken together, our results indicate that Tyr 393 of AGO2 is hyperphosphorylated in response to PTP1B inactivation and may contribute to H-RAS V12 -induced development of senescence.\|We identified phospho-Tyr 393 of argonaute 2 (AGO2) as a direct substrate of PTP1B.	SIGNOR-277120
P54274	Q6IBW4	binding	up-regulates activity	0.2	Taken together these observations suggest that NCAPH2 promotes telomere stability, possibly through a direct interaction with the TRF1 shelterin component, and prevents telomere dysfunction resulting from impaired DNA replication.	SIGNOR-263914
Q9BUF5	Q14980	binding	up-regulates	0.2	Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.	SIGNOR-117109
Q9Y5F9	Q9Y5I2	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-265706
Q15910	Q9C0B5	palmitoylation	down-regulates activity	0.2	Mechanistic investigations revealed that mutant p53 transcriptionally upregulated ZDHHC5 along with the nuclear transcription factor NF-Y. These events contributed to the development of glioma by promoting the self-renewal capacity and tumorigenicity of glioma stem-like cells, by altering the palmitoylation and phosphorylation status of the tumor suppressor EZH2.	SIGNOR-261144
Q5TEC6	Q92830	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
P15336	P07954	binding	up-regulates activity	0.2	Glucose deficiency induces AMPK activation, which phosphorylates FH at Ser75 and promotes its binding to ATF2 and the enrichment of the FH–ATF2 complex on the promoter regions of ATF2-targeted genes.	SIGNOR-266314
Q9BSJ6	Q8TAS1	phosphorylation	up-regulates	0.2	Cats is a substrate of kis and mapped the phosphorylation site to cats serine 131 (s131). Kis enhances the transcriptional repressor activity of cats	SIGNOR-192702
P55075	Q9BYU1	transcriptional regulation	down-regulates quantity by repression	0.2	Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription	SIGNOR-265806
P04114	O60216	transcriptional regulation	down-regulates quantity	0.2	The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector.	SIGNOR-259974
Q13586	Q9Y478	phosphorylation	down-regulates activity	0.2	STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE	SIGNOR-277298
P19086	P43657	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-257120
O75367	O43791	binding	up-regulates activity	0.2	Here, we describe an E3 ubiquitin ligase consisting of SPOP and CULLIN3 that is able to ubiquitinate the PcG protein BMI1 and the variant histone MACROH2A1. BMI1 and MACROH2A1 interact with and are ubiquitinated by the CULLIN3 and SPOP ligase complex.	SIGNOR-272657
Q92911	P27695	transcriptional regulation	up-regulates quantity by expression	0.2	These data demonstrate a role for APE/Ref-1 protein in the transcriptional regulation of NIS gene expression by itself and in cooperation with PAX8.	SIGNOR-261564
P16070	P17612	phosphorylation	up-regulates	0.2	Pka can phosphorylate ser316 directly cd44 s291a and s316a mutants may disrupt downstream signalling events by displacing endogenous cd44 from plasma membrane microdomains.	SIGNOR-147208
Q9BRS8	P42345	phosphorylation	up-regulates activity	0.2	Binding of La ribonucleoprotein domain family, member 6 (LARP6) to collagen mRNAs regulates their translation and is necessary for high type I collagen expression. Here we show that mTORC1 phosphorylates LARP6 on S348 and S409. The S348A/S409A mutant of LARP6 acts as a dominant negative protein in collagen biosynthesis, which retards secretion of type I collagen and causes excessive posttranslational modifications.	SIGNOR-273679
P55268	P31276	transcriptional regulation	up-regulates quantity by expression	0.2	The specificity of binding of these two proteins to the Lamin B2 origin is confirmed by both band-shift and in vitro footprinting assays. In addition, the ability of HOXC10 and HOXC13 to increase the activity of a promoter containing the 74 bp sequence, as assayed by CAT-assay experiments, demonstrates a direct interaction of these homeoproteins with the origin sequence in mammalian cells.	SIGNOR-261644
Q7Z2Y5	Q9UNE7	polyubiquitination	down-regulates quantity by destabilization	0.2	Our results indicate that Nrk is ubiquitinated by CHIP in a chaperone-dependent manner, resulting in its proteasomal degradation.	SIGNOR-274110
Q6NZ36	P49841	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
P15173	Q12857	transcriptional regulation	up-regulates quantity by expression	0.2	NFIA binds to and activates the brown-fat-specific enhancers even before differentiation and later facilitates the binding of PPARgamma\|NFIA has at least three functions on the transcriptional regulation of brown fat [2]. First, NFIA activates adipogenesis per se, through activating the transcription of Pparg, which encodes PPARgamma. Second, NFIA also activates the brown-fat-specific gene expression (such as Ucp1 and Ppargc1a) independent of the degree of adipocyte differentiation, through facilitating the binding of PPARgamma to the brown-fat-specific enhancers. Third, NFIA represses myogenesis through suppression of myogenic transcription factors such as Myod1 as well as Myog,	SIGNOR-263983
P57053	Q14493	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265384
Q96CV9	Q8WV16	binding	up-regulates activity	0.2	DCAF4-mediated ubiquitination of OPTN facilitates the degradation of DBR-exposed SOD1. OPTN is involved in degradation of DBR-exposed SOD1. These data demonstrate that DCAF4-including CRL4 complex mediates OPTN ubiquitination at lysine 501, and this ubiquitination is absent in the ALS-related OPTNmut.	SIGNOR-272210
O14733	Q9NYL2	phosphorylation	up-regulates activity	0.2	We show here that members of the mixed-lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper kinase [DLK]) are expressed in neuronal cells and are likely to act between Rac1/Cdc42 and MKK4 and -7 in death signaling.	SIGNOR-243345
P78559	Q13627	phosphorylation	up-regulates activity	0.2	The phosphorylation of MAP1A and MAP2 by Dyrk1A was further confirmed by immunoprecipitating these proteins from the soluble fraction obtained after phosphorylating MTs (XREF_FIG).	SIGNOR-279032
Q96J92	P12931	phosphorylation	down-regulates activity	0.2	Using Western blot and mass spectrometry, we now identify three sites in WNK4 that are phosphorylated by c-Src: Tyr(1092), Tyr(1094), and Tyr(1143), and show that both c-Src and protein tyrosine phosphatase type 1D (PTP-1D) coimmunoprecipitate with WNK4.	SIGNOR-276897
P31947	P45984	phosphorylation	down-regulates	0.2	Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-189	SIGNOR-124027
Q03113	Q9HC97	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-257204
Q9HD90	Q14938	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268905
O14649	P51812	phosphorylation	up-regulates activity	0.2	The chaperone protein, 14-3-3, binds to a critical phosphorylated serine in the channel c termini of k2p3.1 and k2p9.1 (ser(393) and ser(373), respectively) and overcomes retention in the endoplasmic reticulum by ?COP. We sought to identify the kinase responsible for phosphorylation of the terminal serine in human and rat variants of k2p3.1 and k2p9.1. Adopting a bioinformatic approach, three candidate protein kinases were identified: camp-dependent protein kinase, ribosomal s6 kinase, and protein kinase c.	SIGNOR-172470
P42336	Q13188	phosphorylation	down-regulates activity	0.2	MST1/2 and HGK inhibit catalytic activity of p110α through phosphorylation at T1061	SIGNOR-277922
P35232	P10721	phosphorylation	up-regulates activity	0.2	In this study, we showed that c-Kit associates with PHB to upregulate phospho-PHB in the lipid raft of the plasma membrane.\|c-Kit phosphorylates PHB at the Tyr259 residue.	SIGNOR-278362
Q9H853	Q5SQI0	acetylation	up-regulates quantity by stabilization	0.2	Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.\|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules	SIGNOR-272252
O14929	Q13131	phosphorylation	up-regulates activity	0.2	Together, these results indicate that AMPK phosphorylated DNMT1-Ser730, RBBP7-Ser314, and HAT1-Ser190\|AMPK increased HAT1 activity through phosphorylation of HAT1-Ser190 and RBBP7-Ser314	SIGNOR-264782
P18433	Q86YJ5	ubiquitination	down-regulates quantity by destabilization	0.2	MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.	SIGNOR-271540
P38405	Q96LB2	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-256929
Q14654	Q13557	phosphorylation	down-regulates	0.2	Results showed that activation of camkii triggered dynamin-dependent internalization of k(atp) channels. This process required phosphorylation of threonine at 180 and 224 and an intact (330)yskf(333) endocytosis motif of the k(atp) channel kir6.2 pore-forming subunit.	SIGNOR-200027
Q00535	Q05655	phosphorylation	down-regulates activity	0.2	This generates a binding site for the C2 domain of PKCδ, which in turn phosphorylates CDK5 on T77. The resulting dissociation of the CDK5R1/CDK5 complex abolishes the activity of CDK5.	SIGNOR-277386
P27816	P33981	phosphorylation	down-regulates quantity by destabilization	0.2	We further uncovered that Mps1 is a kinase of MAP4, and E7-MAP4 binding blocks Mps1 phosphorylation of MAP4, thereby interrupting phosphorylation-dependent MAP4 degradation.	SIGNOR-277458
Q71DI3	Q9NRC8	deacetylation	up-regulates activity	0.2	SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation.\|Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression.	SIGNOR-275875
Q16695	Q9BY66	demethylation	up-regulates activity	0.2	KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.	SIGNOR-264309
Q9GZV5	P49841	phosphorylation	down-regulates quantity by destabilization	0.2	GSK3 destabilizes TAZ. TAZS58A/S62A but not the TAZ S66A mutant diminished phos- phorylation by GSK3 , suggesting that Ser-58 and Ser-62 are important for GSK3 phosphorylation, whereas the Ser-66 is not (Fig. 4D).	SIGNOR-277646
P05556	Q9Y5H9	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.	SIGNOR-265661
Q99835	P00450	binding	down-regulates	0.2	Genetic and biochemical studies imply that smo can adopt an active conformation but that it is normally repressed by patched (ptch), a 12-transmembrane protein considered the receptor for hh	SIGNOR-148451
P68431	P49336	phosphorylation	down-regulates activity	0.2	However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo.	SIGNOR-273171
P11908	Q9NRM7	phosphorylation	down-regulates quantity by destabilization	0.2	Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness.	SIGNOR-276507
P18545	P25098	phosphorylation	up-regulates activity	0.2	Mutation of Thr-62 (to Ala) in PDEgamma produced a GRK2 phosphorylation-resistant mutant that was less effective in associating with GRK2 in response to epidermal growth factor and did not potentiate the stimulation of p42/p44 mitogen-activated protein kinase by this growth factor.	SIGNOR-247823
Q6ZN28	O15075	phosphorylation	up-regulates activity	0.2	Subsequently, MACC1 gets phosphorylated by DCLK1.\|This might be attributed to the higher activation of MACC1 by DCLK1 in the MACC1-positive cell lines SW620/Control and SW480/MACC1 used in this study.	SIGNOR-279031
Q04760	Q9UQM7	phosphorylation	up-regulates activity	0.2	This study is able to show that a phosphorylation of threonine-107 (T107) in the (rate-limiting) Glyoxalase 1 (Glo1) protein, mediated by Ca2+/calmodulin-dependent kinase II delta (CamKIIδ), is associated with elevated catalytic efficiency of Glo1 (lower KM; higher Vmax).	SIGNOR-273553
Q13586	Q9UGJ0	phosphorylation	down-regulates activity	0.2	STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE	SIGNOR-277297
P02708	O14904	binding	up-regulates	0.2	We identified five wnts (wnt9a, wnt9b, wnt10b, wnt11, and wnt16) that are able to stimulate achr clustering, of which wnt9a and wnt11 are expressed abundantly in developing muscles.	SIGNOR-195972
P63000	Q6ZNL6	guanine nucleotide exchange factor	up-regulates activity	0.2	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-260555
Q13309	O00755	binding	down-regulates activity	0.2	These findings suggested that Wnt7a upregulated P21 and P27 by inactivating SKP2.	SIGNOR-278876
P42566	O60260	ubiquitination	up-regulates	0.2	Treatment of cells with egf stimulates parkin binding to both eps15 and the egfr and promotes parkin-mediated ubiquitination of eps15	SIGNOR-148218
Q86U86	Q13049	ubiquitination	down-regulates quantity by destabilization	0.2	TRIM32 ubiquitination of PB1 leads to its protein degradation.	SIGNOR-278735
P19174	Q92830	acetylation	down-regulates activity	0.2	The histone acetyltransferase GCN5 (general control non-repressed protein 5) acetylates PGC-1alpha and suppresses its transcriptional activity, whereas sirtuin 1 deacetylates and activates PGC-1alpha.	SIGNOR-275498
Q8N5B7	P68400	phosphorylation	up-regulates activity	0.2	Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue.	SIGNOR-273987
P53396	P07948	phosphorylation	up-regulates activity	0.2	We demonstrate the binding of PIP2 to the CoA-binding domain of ACLY and identify the six tyrosine residues of ACLY that are phosphorylated by Lyn. Three of them (Y682, Y252, Y227) can be also phosphorylated by Src and they are located in catalytic, citrate binding and ATP binding domains, respectively. PI3K and Lyn inhibitors reduce the ACLY enzyme activity, ACLY-mediated Acetyl-CoA synthesis, phospholipid synthesis, histone acetylation and cell growth. Thus, PIP2/PIP3 binding and Src tyrosine kinases-mediated stimulation of ACLY links oncogenic pathways to Acetyl-CoA-dependent pro-growth and survival metabolic pathways in cancer cells.	SIGNOR-274105
Q9ULA0	Q9P286	phosphorylation	down-regulates quantity by destabilization	0.2	We show that PAK5 interacts with and phosphorylates DNPEP at serine 119. \| PAK5 decreases DNPEP abundance via the ubiquitin-proteasome pathway.	SIGNOR-275651
Q05195	Q9UBS0	phosphorylation	down-regulates	0.2	In this study, we showed that mad1 is a substrate of p90 ribosomal kinase (rsk) and p70 s6 kinase (s6k). Both rsk and s6k phosphorylate serine 145 of mad1 upon serum or insulin stimulation. Ser-145 phosphorylation of mad1 accelerates the ubiquitination and degradation of mad1 through the 26s proteasome pathway	SIGNOR-178594
Q9UJT0	Q8IYT4	binding	down-regulates quantity by destabilization	0.2	KATNAL2 does not sever microtubules composed of α- and β-tubulin but does interact with δ- and ε-tubulin	SIGNOR-267176
Q9UBR4	Q92793	binding	up-regulates activity	0.2	Transcription of pituitary alpha-glycoprotein hormone subunit (alpha-GSU) and thyrotropin beta subunit (TSH-beta) genes is stimulated by thyrotropin-releasing hormone (TRH). P-Lim and CBP Act Synergistically in TRH Stimulation of the Human α-GSU Promoter.	SIGNOR-267206
Q9HCX4	Q13976	phosphorylation	up-regulates activity	0.2	In vitro and in vivo kinase assays have revealed that cGK-Iα phosphorylates mouse TRPC7 but not mouse TRPC3. Site-directed mutagenesis analysis revealed that TRPC7 was phosphorylated by cGK-Iα at threonine 15. Phosphorylation of TRPC7 significantly suppressed carbachol-induced calcium influx and CREB phosphorylation. These data indicate that cGK-Iα interacts with and phosphorylates TRPC7, contributing to the quick and accurate regulation of calcium influx and CREB phosphorylation.	SIGNOR-263184
O95837	Q96P68	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-257417
Q8N163	P19784	phosphorylation	up-regulates activity	0.2	CK2alphawas bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2alphawas evidenced by co-immunoprecipitation of CK2alphaand DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. \|In our results, CK2alpha affected the\|These results suggest that DBC1 may be involved in the progression of gastric carcinoma by inducing the EMT and that it is closely associated with CK2alpha-mediated phosphorylation of DBC1. phosphorylation of Thr454 on DBC1	SIGNOR-267667
O00429	Q9NX47	polyubiquitination	down-regulates quantity by destabilization	0.2	We found that MITOL associated with and ubiquitinated mitochondrial fission protein hFis1 and Drp1.Pulse–chase experiment also indicated that MITOL overexpression promoted Drp1 turnover.	SIGNOR-271894
Q9HA82	P68400	phosphorylation	up-regulates activity	0.2	Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue.	SIGNOR-273984
Q06210	Q9UQM7	phosphorylation	up-regulates	0.2	Amp-activated protein kinase and calcium/calmodulin-dependent kinase ii were identified to phosphorylate specifically ser243 in vitro. Phosphorylation by these two kinases results in an increase of enzymatic activity by 1.4-fold. These findings suggest for the first time that hgfat1 may be regulated by kinases other than pka.	SIGNOR-158486
Q9HCP0	Q5JTC6	binding	up-regulates	0.2	Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.	SIGNOR-171889
Q8TCS8	P78527	phosphorylation	up-regulates activity	0.2	We also demonstrated that DNAPK phosphorylates PNPase at Ser-776, which is critical for its ribonuclease activity.	SIGNOR-263182
P23219	Q86UZ6	transcriptional regulation	up-regulates quantity by expression	0.2	ZBTB46 acts as a transcriptional coactivator that binds to the promoter of prostaglandin-endoperoxide synthase 1 (PTGS1) and transcriptionally regulated PTGS1 levels.	SIGNOR-277991
Q14524	Q92914	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-253418
O60260	O75385	phosphorylation	up-regulates activity	0.2	Furthermore, the Parkin band shift induced by catalytically active WT ULK1 was diminished by treatment of cell lysates with lambda-phosphatase, as was the mobility of ULK1 itself (XREF_FIG).\|Parkin is phosphorylated by ULK1 at Ser 108 in its recently described nine amino acid ACT element at this early time point	SIGNOR-279663
P11137	Q9HCK8	transcriptional regulation	down-regulates quantity	0.2	Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells	SIGNOR-268916
P45985	P54762	relocalization	up-regulates activity	0.2	The phosphorylated CNK1 interacts with ephrinB1. The binding of ephrinB1 to CNK1 connects RhoA and p115RhoGEF with ephrinB1-associated MKK4, promoting JNK activation and cell migration.	SIGNOR-275922
Q5SQI0	O43318	phosphorylation	up-regulates activity	0.2	Here we report TGF-beta-activated kinase 1 (TAK1) as a key activator of alphaTAT1. TAK1 directly interacts with and phosphorylates alphaTAT1 at Ser237 to critically enhance its catalytic activity	SIGNOR-272243
P98161	P53355	phosphorylation	up-regulates activity	0.2	In addition, the tumor suppressor death-associated protein kinase phosphorylates and activates PKD1 in response to oxidative damage ( xref ).	SIGNOR-279985
Q86X29	Q14289	phosphorylation	up-regulates activity	0.2	Pyk2 enhances LSR and tricellulin localization to tTJs.\|Pyk2-dependent phosphorylation of LSR enhances localization of LSR and tricellulin at tricellular tight junctions.	SIGNOR-280101
Q03113	Q9BPV8	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-257231
Q13547	Q63HK5	relocalization	up-regulates activity	0.2	We carried out yeast two-hybrid studies with a PTB domain of FE65, focusing on those genes that might be involved in nuclear signaling, and identified and validated Teashirt proteins as FE65 interacting proteins in neurons. Using reporter systems, we observed that FE65 could simultaneously recruit SET, a component of the inhibitor of acetyl transferase, and Teashirt, which in turn recruited histone deacetylases, to produce a powerful gene-silencing complex.Endogenous HDAC1 was co-immunoprecipitated with FE65 when both FE65 and Teashirt3 were co-transfected (lane 4), but not when Teashirt3 or FE65 was omitted (lane 5 and 6), confirming that the association of HDAC1 with FE65 is dependent on, and mediated, by Teashirt3.	SIGNOR-264814
P49959	P68400	phosphorylation	up-regulates activity	0.2	Here we show that MRE11 directly interacts with PIH1D1, a subunit of heat-shock protein 90 cochaperone R2TP complex, which is required for the assembly of large protein complexes, such as RNA polymerase II, small nucleolar ribonucleoproteins and mammalian target of rapamycin complex 1. The MRE11-PIH1D1 interaction is dependent on casein kinase 2 (CK2) phosphorylation of two acidic sequences within the MRE11 C terminus containing serines 558/561 and 688/689.	SIGNOR-265893
Q9Y566	P35637	post transcriptional regulation	up-regulates quantity	0.2	These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.\|As seen in Figure 7 (top panel), both PSD-95 Q1-Q2 and Shank1a GQ probes pulled down endogenous FUS, whereas their M2 mutants did not, indicating that the GQ structure is sufficient for recognition.	SIGNOR-262104
Q99250	P68400	phosphorylation	up-regulates activity	0.2	We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. \| inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G.	SIGNOR-275761
Q14344	P41231	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-257233
P09471	Q96P68	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257243
Q05639	P05771	phosphorylation	up-regulates activity	0.2	PKCβI phosphorylates eEF1A at Ser53.our proteomics exploration of cPKC signaling in the nuclei of C2C12 cells demonstrated that the up-regulation of eEF1A intranuclear content, evoked by insulin, is associated with an increase in the phosphorylation of the Ser53 residue of the protein.	SIGNOR-263166
Q86WV6	Q9BY78	ubiquitination	up-regulates activity	0.2	As a result, knockdown of RNF26 promoted degradation of MITA after viral infection and prevented degradation of IRF3.\|In addition, RNF26 could not induce polyubiquitination of MITA (K150R) in in vitro ubiquitination assays (XREF_FIG).	SIGNOR-278573
Q96CG3	O14965	phosphorylation	up-regulates activity	0.2	Here, we report that Aurora A is essential for Thr9 phosphorylation of the TRAF-interacting protein TIFA, triggering activation of the NF-κB survival pathway in AML.	SIGNOR-273551
P46940	Q8IVH8	phosphorylation	up-regulates activity	0.2	GLK directly phosphorylated IQGAP1 at Ser-480 enhancing Cdc42 activation and subsequent cell migration.	SIGNOR-277479
Q9Y5G4	Q9Y5H9	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-265678
Q5TEC6	Q9UIF8	binding	down-regulates activity	0.2	The BAZ2B bromodomain has been shown to bind to acetylated H3K14 (H3K14ac), whose presence at promoter regions is generally associated with gene activation. This suggests a potential role for BAZ2B in transcriptional activation.	SIGNOR-266618

Q13285

Q9HAZ1

0

phosphorylation

up-regulates activity

0.2

Immunoblotting analyses showed that the phosphorylation status of NR5A1 at Ser203 was attenuated by the CLK1/4 inhibitor.

SIGNOR-274117

Q8TD43

P17252

0

phosphorylation

up-regulates

0.2

Phorbol ester-induced activation of protein kinase c (pkc) increased the ca(2+) sensitivity of wild-type trpm4 but not of two mutants mutated at putative pkc phosphorylation sites.

SIGNOR-132243

Q9P212

Q9UBI6

0

binding

up-regulates

0.2

In the non-canonical wntpathway, frizzled uses galfaq or galfai and gbetagamma dimers to activate phospholipase c (plc), resulting in protein kinase c (pkc) activation and calcium mobilization that regulates the transcription factor nfat, and frizzled also signals through the small gtpases rho and rac to c-jun n-terminal kinase (jnk), which activates the ap1 transcription factor

SIGNOR-152612

Q9P2J5

Q5S007

0

phosphorylation

down-regulates activity

0.2

In this study, we elucidated that leucyl-tRNA synthetase (LRS) was an LRRK2 kinase substrate and identified T293 as an LRRK2 phosphorylation site. LRRK2-meidated LRS phosphorylation or G2019S can lead to impairment of LRS editing, increased ER stress, and accumulation of autophagy markers.

SIGNOR-277417

O15269

P00519

0

phosphorylation

down-regulates

0.2

We demonstrated that the er-resident human protein serine palmitoyltransferase long chain-1 (sptlc1), which is the first enzyme of sphingolipid biosynthesis, is phosphorylated at tyr(164) by the tyrosine kinase abl. this occurred through the specific abl-mediated phosphorylation of sptlc1 on tyr164, leading to the attenuation of its activity.

SIGNOR-202003

Q03113

Q9Y653

0

binding

up-regulates activity

0.2

Binding of collagen III to ADGRG1 provides a canonical example of adhesion GPCR interactions with ECM proteins (Luo et al., 2011). Identified by an in vitro biotinylation/proteomics approach, extracellular interactions with collagen III were subsequently proven capable of activating ADGRG1-mediated signaling via Gα12/13 followed by RhoA activation to regulate corticogenesis

SIGNOR-272344

P68431

Q9UIF8

0

binding

down-regulates activity

0.2

The BAZ2B bromodomain has been shown to bind to acetylated H3K14 (H3K14ac), whose presence at promoter regions is generally associated with gene activation. This suggests a potential role for BAZ2B in transcriptional activation.

SIGNOR-266622

P19367

Q8IYT8

0

phosphorylation

up-regulates activity

0.2

Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).

SIGNOR-274042

P53004

Q05655

0

phosphorylation

up-regulates activity

0.2

LC-MS/MS analysis of PKCdelta-activated intact hBVR identified phosphorylated serine positions 21, 33, 230, and 237, corresponding to the hBVR Src homology-2 domain motif (Ser(230) and Ser(237)), flanking the ATP-binding motif (Ser(21)) and in PHPS sequence (Ser(33)) as targets of PKCdelta. |PKCdelta potentiated hBVR reductase activity and accelerated the rate of bilirubin formation.

SIGNOR-275525

O60216

Q9Y6M0

0

cleavage

up-regulates

0.2

Rad21 is a component of the cohesin complex that holds sister chromatids together during mitosis and repairs double-strand dna breaks. Interestingly, rad21 is cleaved by a caspase-like esp1/separase at the onset of anaphase to trigger sister chromatid separation.

SIGNOR-115426

Q9UKV8

P18031

0

dephosphorylation

down-regulates activity

0.2

Taken together, our results indicate that Tyr 393 of AGO2 is hyperphosphorylated in response to PTP1B inactivation and may contribute to H-RAS V12 -induced development of senescence.|We identified phospho-Tyr 393 of argonaute 2 (AGO2) as a direct substrate of PTP1B.

SIGNOR-277120

P54274

Q6IBW4

0

binding

up-regulates activity

0.2

Taken together these observations suggest that NCAPH2 promotes telomere stability, possibly through a direct interaction with the TRF1 shelterin component, and prevents telomere dysfunction resulting from impaired DNA replication.

SIGNOR-263914

Q9BUF5

Q14980

0

binding

up-regulates

0.2

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

SIGNOR-117109

Q9Y5F9

Q9Y5I2

0

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-265706

Q15910

Q9C0B5

0

palmitoylation

down-regulates activity

0.2

Mechanistic investigations revealed that mutant p53 transcriptionally upregulated ZDHHC5 along with the nuclear transcription factor NF-Y. These events contributed to the development of glioma by promoting the self-renewal capacity and tumorigenicity of glioma stem-like cells, by altering the palmitoylation and phosphorylation status of the tumor suppressor EZH2.

SIGNOR-261144

Q5TEC6

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-269599

P15336

P07954

0

binding

up-regulates activity

0.2

Glucose deficiency induces AMPK activation, which phosphorylates FH at Ser75 and promotes its binding to ATF2 and the enrichment of the FH–ATF2 complex on the promoter regions of ATF2-targeted genes.

SIGNOR-266314

Q9BSJ6

Q8TAS1

0

phosphorylation

up-regulates

0.2

Cats is a substrate of kis and mapped the phosphorylation site to cats serine 131 (s131). Kis enhances the transcriptional repressor activity of cats

SIGNOR-192702

P55075

Q9BYU1

0

transcriptional regulation

down-regulates quantity by repression

0.2

Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription

SIGNOR-265806

P04114

O60216

0

transcriptional regulation

down-regulates quantity

0.2

The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector.

SIGNOR-259974

Q13586

Q9Y478

0

phosphorylation

down-regulates activity

0.2

STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE

SIGNOR-277298

P19086

P43657

0

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-257120

O75367

O43791

0

binding

up-regulates activity

0.2

Here, we describe an E3 ubiquitin ligase consisting of SPOP and CULLIN3 that is able to ubiquitinate the PcG protein BMI1 and the variant histone MACROH2A1. BMI1 and MACROH2A1 interact with and are ubiquitinated by the CULLIN3 and SPOP ligase complex.

SIGNOR-272657

Q92911

P27695

0

transcriptional regulation

up-regulates quantity by expression

0.2

These data demonstrate a role for APE/Ref-1 protein in the transcriptional regulation of NIS gene expression by itself and in cooperation with PAX8.

SIGNOR-261564

P16070

P17612

0

phosphorylation

up-regulates

0.2

Pka can phosphorylate ser316 directly cd44 s291a and s316a mutants may disrupt downstream signalling events by displacing endogenous cd44 from plasma membrane microdomains.

SIGNOR-147208

Q9BRS8

P42345

0

phosphorylation

up-regulates activity

0.2

Binding of La ribonucleoprotein domain family, member 6 (LARP6) to collagen mRNAs regulates their translation and is necessary for high type I collagen expression. Here we show that mTORC1 phosphorylates LARP6 on S348 and S409. The S348A/S409A mutant of LARP6 acts as a dominant negative protein in collagen biosynthesis, which retards secretion of type I collagen and causes excessive posttranslational modifications.

SIGNOR-273679

P55268

P31276

0

transcriptional regulation

up-regulates quantity by expression

0.2

The specificity of binding of these two proteins to the Lamin B2 origin is confirmed by both band-shift and in vitro footprinting assays. In addition, the ability of HOXC10 and HOXC13 to increase the activity of a promoter containing the 74 bp sequence, as assayed by CAT-assay experiments, demonstrates a direct interaction of these homeoproteins with the origin sequence in mammalian cells.

SIGNOR-261644

Q7Z2Y5

Q9UNE7

0

polyubiquitination

down-regulates quantity by destabilization

0.2

Our results indicate that Nrk is ubiquitinated by CHIP in a chaperone-dependent manner, resulting in its proteasomal degradation.

SIGNOR-274110

Q6NZ36

P49841

0

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

P15173

Q12857

0

transcriptional regulation

up-regulates quantity by expression

0.2

NFIA binds to and activates the brown-fat-specific enhancers even before differentiation and later facilitates the binding of PPARgamma|NFIA has at least three functions on the transcriptional regulation of brown fat [2]. First, NFIA activates adipogenesis per se, through activating the transcription of Pparg, which encodes PPARgamma. Second, NFIA also activates the brown-fat-specific gene expression (such as Ucp1 and Ppargc1a) independent of the degree of adipocyte differentiation, through facilitating the binding of PPARgamma to the brown-fat-specific enhancers. Third, NFIA represses myogenesis through suppression of myogenic transcription factors such as Myod1 as well as Myog,

SIGNOR-263983

P57053

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.

SIGNOR-265384

Q96CV9

Q8WV16

0

binding

up-regulates activity

0.2

DCAF4-mediated ubiquitination of OPTN facilitates the degradation of DBR-exposed SOD1. OPTN is involved in degradation of DBR-exposed SOD1. These data demonstrate that DCAF4-including CRL4 complex mediates OPTN ubiquitination at lysine 501, and this ubiquitination is absent in the ALS-related OPTNmut.

SIGNOR-272210

O14733

Q9NYL2

0

phosphorylation

up-regulates activity

0.2

We show here that members of the mixed-lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper kinase [DLK]) are expressed in neuronal cells and are likely to act between Rac1/Cdc42 and MKK4 and -7 in death signaling.

SIGNOR-243345

P78559

Q13627

0

phosphorylation

up-regulates activity

0.2

The phosphorylation of MAP1A and MAP2 by Dyrk1A was further confirmed by immunoprecipitating these proteins from the soluble fraction obtained after phosphorylating MTs (XREF_FIG).

SIGNOR-279032

Q96J92

P12931

0

phosphorylation

down-regulates activity

0.2

Using Western blot and mass spectrometry, we now identify three sites in WNK4 that are phosphorylated by c-Src: Tyr(1092), Tyr(1094), and Tyr(1143), and show that both c-Src and protein tyrosine phosphatase type 1D (PTP-1D) coimmunoprecipitate with WNK4.

SIGNOR-276897

P31947

P45984

0

phosphorylation

down-regulates

0.2

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

SIGNOR-124027

Q03113

Q9HC97

0

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-257204

Q9HD90

Q14938

0

transcriptional regulation

up-regulates quantity

0.2

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268905

O14649

P51812

0

phosphorylation

up-regulates activity

0.2

The chaperone protein, 14-3-3, binds to a critical phosphorylated serine in the channel c termini of k2p3.1 and k2p9.1 (ser(393) and ser(373), respectively) and overcomes retention in the endoplasmic reticulum by ?COP. We sought to identify the kinase responsible for phosphorylation of the terminal serine in human and rat variants of k2p3.1 and k2p9.1. Adopting a bioinformatic approach, three candidate protein kinases were identified: camp-dependent protein kinase, ribosomal s6 kinase, and protein kinase c.

SIGNOR-172470

P42336

Q13188

0

phosphorylation

down-regulates activity

0.2

MST1/2 and HGK inhibit catalytic activity of p110α through phosphorylation at T1061

SIGNOR-277922

P35232

P10721

0

phosphorylation

up-regulates activity

0.2

In this study, we showed that c-Kit associates with PHB to upregulate phospho-PHB in the lipid raft of the plasma membrane.|c-Kit phosphorylates PHB at the Tyr259 residue.

SIGNOR-278362

Q9H853

Q5SQI0

0

acetylation

up-regulates quantity by stabilization

0.2

Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules

SIGNOR-272252

O14929

Q13131

0

phosphorylation

up-regulates activity

0.2

Together, these results indicate that AMPK phosphorylated DNMT1-Ser730, RBBP7-Ser314, and HAT1-Ser190|AMPK increased HAT1 activity through phosphorylation of HAT1-Ser190 and RBBP7-Ser314

SIGNOR-264782

P18433

Q86YJ5

0

ubiquitination

down-regulates quantity by destabilization

0.2

MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.

SIGNOR-271540

P38405

Q96LB2

0

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-256929

Q14654

Q13557

0

phosphorylation

down-regulates

0.2

Results showed that activation of camkii triggered dynamin-dependent internalization of k(atp) channels. This process required phosphorylation of threonine at 180 and 224 and an intact (330)yskf(333) endocytosis motif of the k(atp) channel kir6.2 pore-forming subunit.

SIGNOR-200027

Q00535

Q05655

0

phosphorylation

down-regulates activity

0.2

This generates a binding site for the C2 domain of PKCδ, which in turn phosphorylates CDK5 on T77. The resulting dissociation of the CDK5R1/CDK5 complex abolishes the activity of CDK5.

SIGNOR-277386

P27816

P33981

0

phosphorylation

down-regulates quantity by destabilization

0.2

We further uncovered that Mps1 is a kinase of MAP4, and E7-MAP4 binding blocks Mps1 phosphorylation of MAP4, thereby interrupting phosphorylation-dependent MAP4 degradation.

SIGNOR-277458

Q71DI3

Q9NRC8

0

deacetylation

up-regulates activity

0.2

SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation.|Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression.

SIGNOR-275875

Q16695

Q9BY66

0

demethylation

up-regulates activity

0.2

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

SIGNOR-264309

Q9GZV5

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.2

GSK3 destabilizes TAZ. TAZS58A/S62A but not the TAZ S66A mutant diminished phos- phorylation by GSK3 , suggesting that Ser-58 and Ser-62 are important for GSK3 phosphorylation, whereas the Ser-66 is not (Fig. 4D).

SIGNOR-277646

P05556

Q9Y5H9

0

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.

SIGNOR-265661

Q99835

P00450

0

binding

down-regulates

0.2

Genetic and biochemical studies imply that smo can adopt an active conformation but that it is normally repressed by patched (ptch), a 12-transmembrane protein considered the receptor for hh

SIGNOR-148451

P68431

P49336

0

phosphorylation

down-regulates activity

0.2

However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo.

SIGNOR-273171

P11908

Q9NRM7

0

phosphorylation

down-regulates quantity by destabilization

0.2

Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness.

SIGNOR-276507

P18545

P25098

0

phosphorylation

up-regulates activity

0.2

Mutation of Thr-62 (to Ala) in PDEgamma produced a GRK2 phosphorylation-resistant mutant that was less effective in associating with GRK2 in response to epidermal growth factor and did not potentiate the stimulation of p42/p44 mitogen-activated protein kinase by this growth factor.

SIGNOR-247823

Q6ZN28

O15075

0

phosphorylation

up-regulates activity

0.2

Subsequently, MACC1 gets phosphorylated by DCLK1.|This might be attributed to the higher activation of MACC1 by DCLK1 in the MACC1-positive cell lines SW620/Control and SW480/MACC1 used in this study.

SIGNOR-279031

Q04760

Q9UQM7

0

phosphorylation

up-regulates activity

0.2

This study is able to show that a phosphorylation of threonine-107 (T107) in the (rate-limiting) Glyoxalase 1 (Glo1) protein, mediated by Ca2+/calmodulin-dependent kinase II delta (CamKIIδ), is associated with elevated catalytic efficiency of Glo1 (lower KM; higher Vmax).

SIGNOR-273553

Q13586

Q9UGJ0

0

phosphorylation

down-regulates activity

0.2

STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE

SIGNOR-277297

P02708

O14904

0

binding

up-regulates

0.2

We identified five wnts (wnt9a, wnt9b, wnt10b, wnt11, and wnt16) that are able to stimulate achr clustering, of which wnt9a and wnt11 are expressed abundantly in developing muscles.

SIGNOR-195972

P63000

Q6ZNL6

0

guanine nucleotide exchange factor

up-regulates activity

0.2

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-260555

Q13309

O00755

0

binding

down-regulates activity

0.2

These findings suggested that Wnt7a upregulated P21 and P27 by inactivating SKP2.

SIGNOR-278876

P42566

O60260

0

ubiquitination

up-regulates

0.2

Treatment of cells with egf stimulates parkin binding to both eps15 and the egfr and promotes parkin-mediated ubiquitination of eps15

SIGNOR-148218

Q86U86

Q13049

0

ubiquitination

down-regulates quantity by destabilization

0.2

TRIM32 ubiquitination of PB1 leads to its protein degradation.

SIGNOR-278735

P19174

Q92830

0

acetylation

down-regulates activity

0.2

The histone acetyltransferase GCN5 (general control non-repressed protein 5) acetylates PGC-1alpha and suppresses its transcriptional activity, whereas sirtuin 1 deacetylates and activates PGC-1alpha.

SIGNOR-275498

Q8N5B7

P68400

0

phosphorylation

up-regulates activity

0.2

Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue.

SIGNOR-273987

P53396

P07948

0

phosphorylation

up-regulates activity

0.2

We demonstrate the binding of PIP2 to the CoA-binding domain of ACLY and identify the six tyrosine residues of ACLY that are phosphorylated by Lyn. Three of them (Y682, Y252, Y227) can be also phosphorylated by Src and they are located in catalytic, citrate binding and ATP binding domains, respectively. PI3K and Lyn inhibitors reduce the ACLY enzyme activity, ACLY-mediated Acetyl-CoA synthesis, phospholipid synthesis, histone acetylation and cell growth. Thus, PIP2/PIP3 binding and Src tyrosine kinases-mediated stimulation of ACLY links oncogenic pathways to Acetyl-CoA-dependent pro-growth and survival metabolic pathways in cancer cells.

SIGNOR-274105

Q9ULA0

Q9P286

0

phosphorylation

down-regulates quantity by destabilization

0.2

We show that PAK5 interacts with and phosphorylates DNPEP at serine 119. | PAK5 decreases DNPEP abundance via the ubiquitin-proteasome pathway.

SIGNOR-275651

Q05195

Q9UBS0

0

phosphorylation

down-regulates

0.2

In this study, we showed that mad1 is a substrate of p90 ribosomal kinase (rsk) and p70 s6 kinase (s6k). Both rsk and s6k phosphorylate serine 145 of mad1 upon serum or insulin stimulation. Ser-145 phosphorylation of mad1 accelerates the ubiquitination and degradation of mad1 through the 26s proteasome pathway

SIGNOR-178594

Q9UJT0

Q8IYT4

0

binding

down-regulates quantity by destabilization

0.2

KATNAL2 does not sever microtubules composed of α- and β-tubulin but does interact with δ- and ε-tubulin

SIGNOR-267176

Q9UBR4

Q92793

0

binding

up-regulates activity

0.2

Transcription of pituitary alpha-glycoprotein hormone subunit (alpha-GSU) and thyrotropin beta subunit (TSH-beta) genes is stimulated by thyrotropin-releasing hormone (TRH). P-Lim and CBP Act Synergistically in TRH Stimulation of the Human α-GSU Promoter.

SIGNOR-267206

Q9HCX4

Q13976

0

phosphorylation

up-regulates activity

0.2

In vitro and in vivo kinase assays have revealed that cGK-Iα phosphorylates mouse TRPC7 but not mouse TRPC3. Site-directed mutagenesis analysis revealed that TRPC7 was phosphorylated by cGK-Iα at threonine 15. Phosphorylation of TRPC7 significantly suppressed carbachol-induced calcium influx and CREB phosphorylation. These data indicate that cGK-Iα interacts with and phosphorylates TRPC7, contributing to the quick and accurate regulation of calcium influx and CREB phosphorylation.

SIGNOR-263184

O95837

Q96P68

0

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-257417

Q8N163

P19784

0

phosphorylation

up-regulates activity

0.2

CK2alphawas bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2alphawas evidenced by co-immunoprecipitation of CK2alphaand DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. |In our results, CK2alpha affected the|These results suggest that DBC1 may be involved in the progression of gastric carcinoma by inducing the EMT and that it is closely associated with CK2alpha-mediated phosphorylation of DBC1. phosphorylation of Thr454 on DBC1

SIGNOR-267667

O00429

Q9NX47

0

polyubiquitination

down-regulates quantity by destabilization

0.2

We found that MITOL associated with and ubiquitinated mitochondrial fission protein hFis1 and Drp1.Pulse–chase experiment also indicated that MITOL overexpression promoted Drp1 turnover.

SIGNOR-271894

Q9HA82

P68400

0

phosphorylation

up-regulates activity

0.2

Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue.

SIGNOR-273984

Q06210

Q9UQM7

0

phosphorylation

up-regulates

0.2

Amp-activated protein kinase and calcium/calmodulin-dependent kinase ii were identified to phosphorylate specifically ser243 in vitro. Phosphorylation by these two kinases results in an increase of enzymatic activity by 1.4-fold. These findings suggest for the first time that hgfat1 may be regulated by kinases other than pka.

SIGNOR-158486

Q9HCP0

Q5JTC6

0

binding

up-regulates

0.2

Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.

SIGNOR-171889

Q8TCS8

P78527

0

phosphorylation

up-regulates activity

0.2

We also demonstrated that DNAPK phosphorylates PNPase at Ser-776, which is critical for its ribonuclease activity.

SIGNOR-263182

P23219

Q86UZ6

0

transcriptional regulation

up-regulates quantity by expression

0.2

ZBTB46 acts as a transcriptional coactivator that binds to the promoter of prostaglandin-endoperoxide synthase 1 (PTGS1) and transcriptionally regulated PTGS1 levels.

SIGNOR-277991

Q14524

Q92914

0

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-253418

O60260

O75385

0

phosphorylation

up-regulates activity

0.2

Furthermore, the Parkin band shift induced by catalytically active WT ULK1 was diminished by treatment of cell lysates with lambda-phosphatase, as was the mobility of ULK1 itself (XREF_FIG).|Parkin is phosphorylated by ULK1 at Ser 108 in its recently described nine amino acid ACT element at this early time point

SIGNOR-279663

P11137

Q9HCK8

0

transcriptional regulation

down-regulates quantity

0.2

Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells

SIGNOR-268916

P45985

P54762

0

relocalization

up-regulates activity

0.2

The phosphorylated CNK1 interacts with ephrinB1. The binding of ephrinB1 to CNK1 connects RhoA and p115RhoGEF with ephrinB1-associated MKK4, promoting JNK activation and cell migration.

SIGNOR-275922

Q5SQI0

O43318

0

phosphorylation

up-regulates activity

0.2

Here we report TGF-beta-activated kinase 1 (TAK1) as a key activator of alphaTAT1. TAK1 directly interacts with and phosphorylates alphaTAT1 at Ser237 to critically enhance its catalytic activity

SIGNOR-272243

P98161

P53355

0

phosphorylation

up-regulates activity

0.2

In addition, the tumor suppressor death-associated protein kinase phosphorylates and activates PKD1 in response to oxidative damage ( xref ).

SIGNOR-279985

Q86X29

Q14289

0

phosphorylation

up-regulates activity

0.2

Pyk2 enhances LSR and tricellulin localization to tTJs.|Pyk2-dependent phosphorylation of LSR enhances localization of LSR and tricellulin at tricellular tight junctions.

SIGNOR-280101

Q03113

Q9BPV8

0

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-257231

Q13547

Q63HK5

0

relocalization

up-regulates activity

0.2

We carried out yeast two-hybrid studies with a PTB domain of FE65, focusing on those genes that might be involved in nuclear signaling, and identified and validated Teashirt proteins as FE65 interacting proteins in neurons. Using reporter systems, we observed that FE65 could simultaneously recruit SET, a component of the inhibitor of acetyl transferase, and Teashirt, which in turn recruited histone deacetylases, to produce a powerful gene-silencing complex.Endogenous HDAC1 was co-immunoprecipitated with FE65 when both FE65 and Teashirt3 were co-transfected (lane 4), but not when Teashirt3 or FE65 was omitted (lane 5 and 6), confirming that the association of HDAC1 with FE65 is dependent on, and mediated, by Teashirt3.

SIGNOR-264814

P49959

P68400

0

phosphorylation

up-regulates activity

0.2

Here we show that MRE11 directly interacts with PIH1D1, a subunit of heat-shock protein 90 cochaperone R2TP complex, which is required for the assembly of large protein complexes, such as RNA polymerase II, small nucleolar ribonucleoproteins and mammalian target of rapamycin complex 1. The MRE11-PIH1D1 interaction is dependent on casein kinase 2 (CK2) phosphorylation of two acidic sequences within the MRE11 C terminus containing serines 558/561 and 688/689.

SIGNOR-265893

Q9Y566

P35637

0

post transcriptional regulation

up-regulates quantity

0.2

These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.|As seen in Figure 7 (top panel), both PSD-95 Q1-Q2 and Shank1a GQ probes pulled down endogenous FUS, whereas their M2 mutants did not, indicating that the GQ structure is sufficient for recognition.

SIGNOR-262104

Q99250

P68400

0

phosphorylation

up-regulates activity

0.2

We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G.

SIGNOR-275761

Q14344

P41231

0

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-257233

P09471

Q96P68

0

binding

up-regulates activity

0.2

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

SIGNOR-257243

Q05639

P05771

0

phosphorylation

up-regulates activity

0.2

PKCβI phosphorylates eEF1A at Ser53.our proteomics exploration of cPKC signaling in the nuclei of C2C12 cells demonstrated that the up-regulation of eEF1A intranuclear content, evoked by insulin, is associated with an increase in the phosphorylation of the Ser53 residue of the protein.

SIGNOR-263166

Q86WV6

Q9BY78

0

ubiquitination

up-regulates activity

0.2

As a result, knockdown of RNF26 promoted degradation of MITA after viral infection and prevented degradation of IRF3.|In addition, RNF26 could not induce polyubiquitination of MITA (K150R) in in vitro ubiquitination assays (XREF_FIG).

SIGNOR-278573

Q96CG3

O14965

0

phosphorylation

up-regulates activity

0.2

Here, we report that Aurora A is essential for Thr9 phosphorylation of the TRAF-interacting protein TIFA, triggering activation of the NF-κB survival pathway in AML.

SIGNOR-273551

P46940

Q8IVH8

0

phosphorylation

up-regulates activity

0.2

GLK directly phosphorylated IQGAP1 at Ser-480 enhancing Cdc42 activation and subsequent cell migration.

SIGNOR-277479

Q9Y5G4

Q9Y5H9

0

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-265678

Q5TEC6

Q9UIF8

0

binding

down-regulates activity

0.2

The BAZ2B bromodomain has been shown to bind to acetylated H3K14 (H3K14ac), whose presence at promoter regions is generally associated with gene activation. This suggests a potential role for BAZ2B in transcriptional activation.

SIGNOR-266618