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
P17612	Q15208	1	phosphorylation	down-regulates activity	0.295	GSK-3β phosphorylated STK38 on residues S6 and T7 in vitro, depending largely on a PKA-mediated priming phosphorylation of STK38 on residues S10 and S11, respectively. Our results indicate that that GSK-3β inhibits STK38's full activation, and suggest that STK38 activation is required to prevent cell death in response to oxidative stress.	SIGNOR-276390
O95352	Q9H492	2	binding	up-regulates	0.872	Lc3-i is activated by the same atg7 involved in atg12 conjugation, transferred to atg3, a second e2-like enzyme, and finally conjugated to pe	SIGNOR-195236
Q16581	P01024	2	binding	up-regulates activity	0.734	A cDNA clone encoding the human C3a anaphylatoxin receptor (C3aR) was isolated from a pcDNAI/Amp expression library prepared from U-937 cells\|The cDNA clone contained an insert of 4.3 kbp and was able to confer to transfected human HEK-293 cells the capacity to bind specifically iodinated human C3a.	SIGNOR-263451
P52803	P54764	2	binding	up-regulates	0.945	Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor	SIGNOR-52473
P54274	Q13315	0	phosphorylation	up-regulates activity	0.571	Telomeric protein pin2/trf1 as an important atm target in response to double strand dna breaks. activated atm directly phosphorylated pin2/trf1 preferentially on the conserved ser(219)-gln site in vitro and in vivo.	SIGNOR-108419
Q9C0A6	Q16695	1	methylation	up-regulates activity	0.2	SETD5 Exhibits Intrinsic Methyltransferase Activity on H3K36. This assay showed that SETD5 has specific histone methyltransferase activity toward K36 but not for other residues such as K4 and K27 (Figure 8B). we revealed that SETD5 is endowed with H3K36 methyltransferase, which is necessary for RNA elongation and processing and, ultimately, correct gene transcription.	SIGNOR-264621
Q13043	O95835	1	phosphorylation	up-regulates	0.623	We show that Mst2 and hWW45 interact with each other in human cells and that both Mst2 and Mst1 are able to phosphorylate Lats1 and Lats2, thereby stimulating Lats kinase activity.	SIGNOR-133551
Q9H2X6	P26367	1	phosphorylation	up-regulates activity	0.463	HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300. Mass spectrometric analysis identified three Pax6 phosphorylation sites as threonines 281, 304, and 373.	SIGNOR-251271
P33076	P42224	0	transcriptional regulation	up-regulates	0.539	When IFN-γ binds to its receptor, the receptor-associated protein tyrosine kinases Janus kinase I (JAK1) and JAK2 are activated (37). This leads to the phosphorylation of STAT1, which then dimerizes, translocates to the nucleus, and activates its target promoters, including the pIV promoter of Ciita	SIGNOR-256249
P35568	O14733	0	phosphorylation	down-regulates activity	0.369	Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223 Ser312 can be phosphorylated by kinases, such as c-jun NH2-terminal kinase and inhibitor of _B kinase	SIGNOR-217920
O43561	Q9H093	0	phosphorylation	down-regulates activity	0.2	Analysis by an in vitro kinase assay revealed that NUAK2 could phosphorylate immunoprecipitated LATS and that this phosphorylation was lost in the LATS double mutant (DM), T246A/S613A (Fig.\u00a0 xref ).\|We showed that phosphorylation of Ser613, located upstream of the KD, adjacent to the MOB binding site and to a lesser extent the N-terminal localized T246, are required for NUAK2 to inhibit LATS.	SIGNOR-280052
P51812	P04637	1	phosphorylation	up-regulates activity	0.336	Here we show that ribosomal S6 kinase 2 (RSK2) activates and phosphorylates p53 (Ser15) in vitro and in vivo and colocalizes with p53 in the nucleus.	SIGNOR-279567
P42229	P60484	0	dephosphorylation	down-regulates	0.439	The forced expression of pten in the eol-1r cells dephosphorylated akt, erk and stat5 /eol-1r cells showed epigenetic silencing of the phosphatase and tensin homolog deleted on chromosome ten (pten) gene. Exposure of eol-1r cells to imatinib failed to dephosphorylate akt, erk and stat5, although pdgfr? Was effectively inactivated. The forced expression of pten negatively regulated these signal pathways and sensitized eol-1r cells to imatinib.	SIGNOR-166481
O15151	P06493	0	phosphorylation	down-regulates	0.407	Cdc2p34 phosphorylates mdmx on ser 96 in vitro. Mutation within this site (mdmx(s96a)) impairs, whereas phosphomimic substitution (mdmx(s96d)) increases the cytoplasmic localization of mdmx, suggesting that cdk2/cdc2p34 phosphorylation is required for export of mdmx from the nucleus	SIGNOR-134388
O14965	Q9Y6A5	1	phosphorylation	up-regulates activity	0.937	We show that this conserved serine on human TACC3 (Ser(558)) is also phosphorylated by Aurora A. Moreover, phosphorylation of TACC3 by Aurora A in human cells is essential for its proper localization to centrosomes and proximal mitotic spindles. Inhibition of Aurora A with the selective small molecule inhibitor MLN8054 in cultured human tumor cells resulted in mislocalization of TACC3 away from mitotic spindles in a concentration-dependent manner.	SIGNOR-262655
Q13501	P46934	0	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
Q9UQD0	P0DP24	2	binding	down-regulates activity	0.45	Here we show that calmodulin (CaM), a ubiquitous Ca2+-sensing protein, binds to the carboxy-terminal 'IQ' domain of the human cardiac Na channel (hH1) in a Ca2+-dependent manner. This binding interaction significantly enhances slow inactivation-a channel-gating process linked to life-threatening idiopathic ventricular arrhythmias.	SIGNOR-266330
Q6PKX4	P07949	2	binding	up-regulates	0.647	These data identify dok-6 as a novel dok-4/5-related adaptor molecule that may function in vivo to transduce signals that regulate ret-mediated processes such as axonal projection.	SIGNOR-127382
Q86Y01	Q09472	2	binding	up-regulates	0.381	We found that a significant fraction of dtx1 proteins were localized in the nucleus and physically interacted with the transcriptional coactivator p300.	SIGNOR-110629
P08183	O94952	2	binding	down-regulates quantity by destabilization	0.325	Here we demonstrate that a ubiquitin E3-ligase, FBXO21, targets the multidrug resistance transporter, ABCB1, also known as P-glycoprotein (P-gp), for proteasomal degradation.Purified in vitro translated FLAG-tagged P-gp along with E2 (UbcH5c), E3 ligase FBXO21, Cul1, Skp1, Roc1 purified from Sf-9 insect cells were incubated in vitro.	SIGNOR-272422
Q14344	P25116	2	binding	up-regulates	0.599	The protease-activated receptors (PAR)2 are a class of G protein-coupled receptors (GPCR) that are activated by the proteolysis of the N-terminal exodomain. Upon proteolysis, the newly formed n terminus acts as a tethered ligand that activates the receptor and initiates signaling cascades through multiple g proteins (galfaq, galfai, and galfa12/13).	SIGNOR-196006
Q13315	Q9Y6D9	1	phosphorylation	up-regulates activity	0.2	ATM mediated Mad1 Serine 214 phosphorylation regulates Mad1 dimerization and the spindle assembly checkpoint.\|Together, these findings reveal an important role of ATM-mediated Mad1 Serine 214 phosphorylation in mitosis.	SIGNOR-278467
Q15058	O43663	2	binding	up-regulates activity	0.634	KIF14 interacts with PRC1 and citron kinase. We find that KIF14 targets to the central spindle via its interaction with PRC1 and has an essential function in cytokinesis. I	SIGNOR-266423
O14843	P08754	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256821
Q9BRS8	P08670	2	binding	up-regulates activity	0.271	Interaction of LARP6 with vimentin.Here, we report that vimentin filaments associate with collagen mRNAs in a 5'SL- and LARP6-dependent manner and stabilize collagen mRNAs. LARP6 interacts with vimentin filaments through its La domain and colocalizes with the filaments in vivo.	SIGNOR-277624
O60603	P58753	2	binding	up-regulates activity	0.726	To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group	SIGNOR-266745
P68400	P27540	1	phosphorylation	down-regulates	0.34	Here, we show that arnt and alt arnt proteins are differentially phosphorylated by protein kinase ckii in vitro. Phosphorylation had an inhibitory effect on dna-binding to an e-box probe by alt arnt, but not arnt, homodimers. This inhibitory phosphorylation occurs through ser77.	SIGNOR-140034
P28360	P56178	2	binding	down-regulates activity	0.389	We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities.	SIGNOR-240987
P31749	Q96HP0	1	phosphorylation	up-regulates activity	0.372	Akt and PP2A reciprocally regulate the guanine nucleotide exchange factor Dock6 to control axon growth of sensory neurons\|At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser(1194). \| In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, whereas reintroduction of Dock6 with a phosphomimetic S1194E mutation resulted in premature branching	SIGNOR-275666
P50542	Q13315	0	phosphorylation	up-regulates activity	0.497	Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor protein p62, directing the autophagosome to peroxisomes to induce pexophagy.	SIGNOR-262792
Q13950	P46937	2	binding	down-regulates	0.449	Here we show that the endogenous yes-associated protein (yap), a mediator of src/yes signaling, interacts with the native runx2 protein, an osteoblast-related transcription factor, and suppresses runx2 transcriptional activity in a dose-dependent manner.	SIGNOR-195221
P35813	O15169	1	dephosphorylation	down-regulates	0.435	Pp2c utilizes axin as a substrate both in vitro and in vivo and decreases its half-life. These results indicate that pp2c is a positive regulator of wnt signal transduction and mediates its effects through the dephosphorylation of axin.	SIGNOR-74231
P49840	Q6R327	1	phosphorylation	down-regulates quantity by destabilization	0.387	We show that this process is dependent on glycogen synthase kinase 3 (GSK3): GSK3 was associated with rictor and directly phosphorylated the Thr-1695 site in a putative CDC4 phospho-degron motif of rictor; mutation of this site impaired the interaction between rictor and FBXW7, decreased rictor ubiquitination, and increased rictor stability.	SIGNOR-276899
P45983	Q9NR28	1	phosphorylation	up-regulates activity	0.371	JNK1\u2011mediated phosphorylation of Smac/DIABLO at the serine 6 residue is functionally linked to its mitochondrial release during TNF\u2011\u03b1-\u2011induced apoptosis of HeLa cells.	SIGNOR-280029
P00519	Q12923	0	dephosphorylation	down-regulates activity	0.39	We also found that PTPN13 dephosphorylates and inhibits c-Abl.\|While the above results indicated that calpain-2 could cleave PTPN13 and that PTPN13 could dephosphorylate c-Abl at tyrosine 245, they did not determine whether calpain-2-mediated cleavage of PTPN13 resulted in its inactivation and increased tyrosine phosphorylation of c-Abl at tyrosine 245.	SIGNOR-277012
P15172	P30281	1	transcriptional regulation	up-regulates quantity by expression	0.374	Here we report that, at the onset of differentiation, activation by MyoD of the Rb, p21, and cyclin D3 genes occurs in the absence of new protein synthesis and with the requirement of the p300 transcriptional coactivator.	SIGNOR-238526
Q13131	P60891	1	phosphorylation	down-regulates activity	0.2	We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production.	SIGNOR-265729
O00470	P31269	2	binding	up-regulates activity	0.62	We now show that the Hoxa-9 protein physically interacts with Meis1 proteins. Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.	SIGNOR-241162
Q14938	P55317	2	binding	up-regulates	0.335	Androgen receptor (ar) action throughout prostate development and in maintenance of the prostatic epithelium is partly controlled by interactions between ar and forkhead box (fox) transcription factors, particularly foxa1./ Foxa1 is capable of bringing ar and nfix into proximity, indicating that foxa1 facilitates the ar and nfi interaction by bridging the complex.	SIGNOR-205082
P46934	Q96NT3	1	polyubiquitination	down-regulates quantity by destabilization	0.419	The E3 ligase NEDD4 regulates GUCD1 degradation. many polyubiquitinylated species of GUCD1 appeared as high molecular weight forms, suggesting that GUCD1 is degraded by the proteasome, after polyubiquitin chain formation, in the presence of NEDD4-1.	SIGNOR-272846
P23443	Q92519	1	phosphorylation	down-regulates quantity by destabilization	0.356	Furthermore, Smurf1-mediated ubiquitination required phosphorylation of TRIB2 by p70 S6 kinase (p70S6K) via another domain (amino acids 69-85) that is also essential for correct TRIB2 subcellular localization. Mutation of Ser-83 diminished p70S6K-induced phosphorylation of TRIB2.	SIGNOR-275433
P12931	P51692	1	phosphorylation	up-regulates	0.578	Stat5 is activated by a broad spectrum of cytokines, as well as non-receptor tyrosine kinases, such as src. these conformational differences may in part be due to differential effects of prl and src on stat5b tyrosine phosphorylation, since src induced several additional sites of tyrosine phosphorylation of stat5b at residues other than tyr-699, including tyr-724 and tyr-679.	SIGNOR-99002
O43432	Q6P2M8	0	phosphorylation	up-regulates	0.2	Here we report that activity-dependent translational initiation in cultured rat hippocampal neurons is enhanced by camki-mediated phosphorylation of ser1156 in eukaryotic initiation factor eif4gii (4gii).	SIGNOR-197190
P49841	P35568	1	phosphorylation	down-regulates quantity by destabilization	0.454	HG activates GSK3beta, which phosphorylates IRS1 at serine 332, leading to the ubiquitination and proteasome mediated degradation of IRS1.	SIGNOR-279183
P01019-PRO_0000032457	Q9BYF1	2	binding	up-regulates activity	0.2	At first, ACE2 has been demonstrated to induce conversion of Ang I into Ang (1–7) by means of intermediate production of Ang (1–9), a fragment with unknown function.	SIGNOR-260226
P00441	O96017	0	phosphorylation	up-regulates activity	0.376	ROS signaling is mediated by Mec1/ATM and its effector Dun1/Cds1 kinase, through Dun1 interaction with Sod1 and regulation of Sod1 by phosphorylation at S60, 99. In the nucleus, Sod1 binds to the promoters and regulates the expression of oxidative resistance and repair genes.	SIGNOR-262794
P46527	P31749	0	phosphorylation	down-regulates	0.85	Because Thr198-phosphorylated p27Kip1 was localized only in the cytoplasm, Akt might promote 14-3-3 binding to p27Kip1 by phosphorylation at Thr198, allowing its cytoplasmic localization and degradation.	SIGNOR-88294
P06213	Q14449	2	binding	down-regulates activity	0.761	Growth factor receptor-bound protein 14 (Grb14) interacts with insulin receptor (IR) through the between PH and SH2 (BPS) domain. Grb14-IR complex formation is initiated by insulin stimulation, and the binding event results in the inhibition of insulin signalling.	SIGNOR-264873
P17861	P17861	2	binding	up-regulates activity	0.2	E4BP4, ATF-6, OASIS, and XBP-1 all formed strong homodimeric associations on the array Transcription factor dimerization can increase the selectivity of protein-DNA interactions and generate a large amount of DNA binding diversity from a relatively small number of proteins	SIGNOR-224199
Q9GZV5	Q06710	2	binding	up-regulates	0.303	Taz is a coactivator for pax8 and ttf-1, two transcription factors involved in thyroid differentiation. / we show that this interaction leads to a significant enhancement of the transcriptional activity of pax8 and ttf-1 on the thyroglobulin promoter thus suggesting a role of taz in the control of genes involved in thyroid development and differentiation.	SIGNOR-182253
P20042	Q9NR50	0	guanine nucleotide exchange factor	up-regulates activity	0.848	EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.	SIGNOR-269131
Q12834	Q16763	2	binding	up-regulates activity	0.872	Ube2S depends on the cell cycle-dependent association with the APC/C activators Cdc20 and Cdh1 for its activity	SIGNOR-265082
P23443	P62753	1	phosphorylation	up-regulates activity	0.937	A knockin mouse carrying mutations at all phosphorylation sites in the primary s6k substrate, ribosomal protein s6 (rps6), has provided insight into the physiological role of this protein phosphorylation event. Of the many known substrates of s6k1, it is rps6 that has been shown to be directly involved, via its phosphorylation, in controlling cell size.	SIGNOR-135176
Q8WW43	Q92542	2	binding	up-regulates	0.94	By using co-immunoprecipitation and nickel affinity pull-down approaches, we now show that mammalian aph-1 (maph-1), a conserved multipass membrane protein, physically associates with nicastrin and the heterodimers of the presenilin amino- and carboxyl-terminal fragments in human cell lines and in rat brain.These data indicate that maph-1 is probably a functional component of the gamma-secretase complex	SIGNOR-93307
P30411	Q03113	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-257344
P15391	P20023	2	binding	up-regulates activity	0.783	Complement receptor type 2 (CR2)/CD21 plays a key role in the development of high-affinity Abs and long-lasting memory to foreign Ags. When CR2 is bound by its primary C3 activation fragment–derived ligand, designated C3d, it coassociates with CD19 on B cells to amplify BCR signaling.	SIGNOR-266642
O95967	P15502	2	binding	up-regulates activity	0.557	Fibulin-4 directly binds LOX, and this interaction enhances fibulin-4 binding to tropoelastin, thus forming a ternary complex that may be critical for elastin cross-linking.	SIGNOR-252136
P46527	O15297	0	dephosphorylation	down-regulates activity	0.259	Increased expression of wildtype WIP1 reduces stability of p27 Kip1 while increased expression of similar amounts of phosphatase-dead WIP1 has no effect on p27 Kip1 protein stability.\|We demonstrate that wildtype, but not phosphatase-dead WIP1, efficiently dephosphorylates p27 Kip1 Ser140 both in vitro and in cells and that this dephosphorylation is sensitive to the WIP1 specific inhibitor GSK 2830371.	SIGNOR-277109
O95319	P12931	0	phosphorylation	up-regulates activity	0.321	Site-directed mutagenesis of putative tyrosine phosphorylation sites in CUGBP2 identified tyrosine 39 as a c-Src target, and a CUGBP2 with a mutated tyrosine 39 displayed an attenuated ability to bind COX-2 mRNA.	SIGNOR-263195
P28347	P46937	2	binding	up-regulates	0.905	When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead14.	SIGNOR-201465
Q13315	Q9H7Z6	1	phosphorylation	up-regulates activity	0.469	In this study we present evidence that MOF is phosphorylated at the threonine 392 residue (pT392-MOF) by ATM subsequent to IR induced DNA damage.\|Interestingly, ATM dependent-MOF phosphorylation increases MOF retention on DNA post-irradiation in S/G2-phase cells.	SIGNOR-278350
Q8NFZ3	Q9Y4C0	2	binding	up-regulates activity	0.2	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264163
Q86T96	O95409	1	ubiquitination	down-regulates quantity by destabilization	0.374	Rinescan directly interact with Zic2. the ubiquitination of endogenous Zic2 was enhanced by Myc-Rines in rat neural stem cellline MNS70 cells. Rines-induced degradation of Zic2	SIGNOR-226303
P63096	P12931	2	binding	up-regulates activity	0.486	Here we demonstrate that Galphas and Galphai, but neither Galphaq, Galpha12 nor Gbetay, directly stimulate the kinase activity of downregulated c-Src	SIGNOR-256526
Q15208	Q96QF0	1	phosphorylation	up-regulates activity	0.366	We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation.	SIGNOR-263036
O14874	P12931	0	phosphorylation	up-regulates activity	0.2	Src phosphorylated BCKDK at the tyrosine 246 (Y246) site in vitro and ex vivo. Knockdown and knockout of Src downregulated the phosphorylation of BCKDK. Importantly, phosphorylation of BCKDK by Src enhanced the activity and stability of BCKDK, thereby promoting the migration, invasion, and EMT of CRC cells.	SIGNOR-275583
P29350	Q12809	1	dephosphorylation	down-regulates	0.2	Our results show that erg-1 is a shp-1 substrate constituting the first report that an ion current is regulated by shp-1.	SIGNOR-94007
P48730	P17302	1	phosphorylation	up-regulates activity	0.6	We have examined the role of casein kinase 1 (CK1) in connexin-43 (Cx43) gap junction assembly. Cellular co-immunoprecipitation experiments and in vitro CK1 phosphorylation reactions indicate that CK1 interacted with and phosphorylated Cx43, initially on serine(s) 325, 328, or 330.\| To examine CK1 function, normal rat kidney cells were treated with CKI-7, and Cx43 content was analyzed by Triton X-100 extraction, cell-surface biotinylation, and immunofluorescence. Western blot analysis indicated a slight increase in total Cx43, whereas gap junctional (Triton-insoluble) Cx43 decreased, and non-junctional plasma membrane Cx43 increased (as detected by cell surface biotinylation).	SIGNOR-249331
P11142	O95817	2	binding	up-regulates activity	0.788	Heat shock cognate protein 70 (Hsc70) regulates protein homeostasis through its reversible interactions with client proteins. Hsc70 has two major domains: a nucleotide-binding domain (NBD), that hydrolyzes ATP, and a substrate-binding domain (SBD), where clients are bound. Members of the BAG family of co-chaperones, including Bag1 and Bag3, are known to accelerate release of both ADP and client from Hsc70.	SIGNOR-254116
O60346	P05771	1	dephosphorylation	down-regulates quantity	0.341	Here we show that the two PHLPP isoforms, PHLPP1 and PHLPP2, also dephosphorylate the hydrophobic motif on PKC betaII, an event that shunts PKC to the detergent-insoluble fraction, effectively terminating its life cycle	SIGNOR-237047
P49715	P35712	0	transcriptional regulation	up-regulates quantity by expression	0.292	We found that SOX6 regulates adipogenesis in vertebrate species by activating adipogenic regulators including PPARγ, C/EBPα and MEST	SIGNOR-255824
O76070	P25098	0	phosphorylation	down-regulates activity	0.2	GRK-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and PLD2. Mutation of Ser124 dramatically inhibits γ-synuclein phosphorylation by GRK2	SIGNOR-251204
P41279	P36507	1	phosphorylation	up-regulates	0.436	Cot proteins were used in an in vitro kinase assay using mek as a substrate. Samples were analyzed by western blotting. As seen in the cascade activity assay only wild-type cot was active against mekregulation of cot is of great interest to the signaling field since the cot/mek/erk pathway potentially plays a role in the etiology of inflammatory autoimmune diseases.	SIGNOR-129694
Q7L2Z9	P53350	0	phosphorylation	down-regulates quantity by destabilization	0.588	Notably, although Plk1 did not alter the level of PBIP1 and CENP-Q ubiquitination, Plk1-dependent phosphorylation and delocalization of these proteins from kinetochores appeared to indirectly lead to their degradation in the cytosol. From these analyses, we identified nine CENP-Q residues (Thr-123, Thr-135, Ser-138, Ser-139, Ser-248, Ser-249, Ser-253, Ser-255, and Thr-256) that were phosphorylated in both in vitro and in vivo samples (Fig. 4B), suggesting that Plk1 phosphorylates these sites.	SIGNOR-265227
Q15208	Q9BX46	1	phosphorylation	up-regulates activity	0.355	Phosphorylation of Rbm24 by Stk38 is crucial for the maintenance of cardiac sarcomeric gene expression in cardiac cells.\|These results indicated that Stk38 increases Rbm24 protein stability probably by interfering with the ubiquitin-proteasome protein degradation pathway.	SIGNOR-278291
Q13418	E9PAV3	1	phosphorylation	up-regulates	0.426	The inactivation of gsk3? In response to adhesion and ilk activation (6) would then result in a thr-159-hypophosphorylated ?-Nac that would become unavailable for proteasome degradation but would become a substrate for the ilk kinase activity on residue ser-43. The ser-43-phosphorylated ?-Nac would preferentially interact with c-jun (30), translocate to the nucleus, and potentiate transcription	SIGNOR-127631
P51812	P03372	1	phosphorylation	up-regulates	0.403	S6k1 regulates estrogen receptor alpha (eralpha) by phosphorylating it on serine 167, leading to transcriptional activation of eralpha.	SIGNOR-182958
Q13309	Q8WWM9	2	binding	down-regulates quantity by destabilization	0.2	Skp2 induces ubiquitin-dependent degradation of Cygb. To this end, we performed an in vivo ubiquitination assay in HEK293T cells by transfecting relevant plasmids as indicated. The V5-Skp2DN was generated by deleting the N-terminal residues from 1 to 153 containing the F-box domain, which is involved in recruiting Skp2 to the SCF complex.	SIGNOR-272792
P25942	P29965	2	binding	up-regulates activity	0.929	Ramos cells were mixed with increasing numbers of transfected cells that expressed cd70 (cd27l) or cd154 (cd40l), both of which are expressed by activated T cells, in the presence of anti-igm ab. Cd27 ligation as well as cd40 ligation inhibited bcr-mediated apoptosis in a dose-dependent manner. cd40 binds its ligand cd40l.	SIGNOR-93432
P46663	P38405	2	binding	up-regulates activity	0.25	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256907
P24941	Q16204	1	phosphorylation	up-regulates	0.2	Serine 244 phosphorylation is required for h4 apoptotic function.	SIGNOR-121198
P48729	Q13158	1	phosphorylation	down-regulates activity	0.333	FADD is essential for death receptor (DR)-induced apoptosis.\|Phosphorylation of FADD at serine 194 by CKIalpha regulates its nonapoptotic activities	SIGNOR-139307
P78371	Q15418	0	phosphorylation	up-regulates	0.249	Furthermore, both the s260a and s260d mutants showed a decreased folding capacity as compared to cells expressing the wild-type cct_ subunit ( fig.?_5e), suggesting that a cyclic phosphorylation of the s260 site by s6k1 is likely to be important for chaperonin function and that mutation of this site interferes with this process.	SIGNOR-172986
Q8TEK3	O75592	1	transcriptional regulation	down-regulates quantity by repression	0.2	Overexpression of DOT1L decreased the expression of HECTD4 and MYCBP2 in LNCaP, C42B, and 22rv1 cells (Supplementary Fig. 5c), suggesting that DOT1L plays a role in repressing these targets either directly or indirectly.	SIGNOR-267151
P08631	P08631	2	phosphorylation	up-regulates activity	0.2	Hck transiently expressed in human embryonic kidney 293T cells was found to be phosphorylated at Tyr-29 and Tyr-388, proving that Hck can also undergo autophosphorylation at both sites in vivo. autophosphorylation of Tyr-29 contributes significantly to the activation of Hck.	SIGNOR-251266
P16410	P06239	0	phosphorylation	up-regulates quantity by stabilization	0.749	Lck and Fyn, but not ZAP70, induce tyrosine phosphorylation of CTLA-4 in the cell line HEK293. Phosphorylation of CTLA-4 occurs on both Y201 and Y218. Phosphorylation of Y201 correlated with accumulation of CTLA-4 on the cell surface.	SIGNOR-251370
O95466	Q05655	0	phosphorylation	up-regulates activity	0.27	PKC\u03b4 induces FMNL1 phosphorylation.	SIGNOR-279261
P06239	P15941	1	phosphorylation	up-regulates activity	0.46	The present results demonstrate that Lck phosphorylation of MUC1 on Y-46 also increases binding of MUC1 and beta-catenin. The results further show that ZAP-70 phosphorylation of MUC1-CD stimulates the interaction of MUC1 and beta-catenin	SIGNOR-249358
P68871	O95600	0	transcriptional regulation	down-regulates quantity by repression	0.2	These results establish KLF8 as a CACCC-box binding protein that associates with CtBP and represses transcription.	SIGNOR-266052
Q9NR19	P08236	1	transcriptional regulation	up-regulates quantity by expression	0.262	Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy\|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1\|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants	SIGNOR-276554
Q15746	P12931	0	phosphorylation	up-regulates	0.417	Ec mlck-1 is phosphorylated by p60(src) on tyr(464) and tyr(471), resulting in a 2- to 3-fold increase in ec mlck-1 enzymatic activity.	SIGNOR-85009
Q9NWQ8	P06241	0	phosphorylation	up-regulates activity	0.703	Thus, Fyn mediates Csk-binding protein-Csk interaction and recruits Csk to rafts by phosphorylating Csk-binding protein.	SIGNOR-279987
P05231	O95644	0	transcriptional regulation	up-regulates quantity by expression	0.415	The calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway has been found to play a role in regulating growth and differentiation in several cell types. However, the functional significance of NFAT in the vasculature is largely unclear. Here we show that NFATc1, NFATc3, and NFATc4 are expressed in human myometrial arteries. \|Chronic inhibition of NFAT significantly reduced IL-6 production in intact myometrial arteries and inhibited cell proliferation in vascular smooth muscle cells cultured from explants from the same arteries.	SIGNOR-251730
Q13555	Q4G163	1	phosphorylation	down-regulates activity	0.2	Activated CaMKII and polo-like kinase simultaneously phosphorylate and inactivate Emi2 [ xref , xref , xref , xref , xref ]).	SIGNOR-280200
Q7Z3K3	P45973	2	binding	down-regulates activity	0.433	POGZ was found to bind to HP1alpha through a zinc-finger-like motif. Binding by POGZ, mediated through its zinc-finger-like motif, competed with PxVxL proteins and destabilized the HP1alpha-chromatin interaction.	SIGNOR-264487
Q92574	P54646	0	phosphorylation	up-regulates	0.551	Under energy starvation conditions, the amp-activated protein kinase (ampk) phosphorylates tsc2 and enhances its activity.	SIGNOR-119541
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
P16519	P01178-PRO_0000020495	1	cleavage	up-regulates quantity	0.2	Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.	SIGNOR-270335
Q96PU5	P43004	1	ubiquitination	down-regulates quantity	0.304	Our results confirm that Nedd4-2 knockdown in MPTP treated mice increased GLT-1 expression at the membrane protein level (XREF_FIG; P < 0.01).\|These results suggest that Nedd4-2 mediates the ubiquitination of both GLT-1 and GLAST in the midbrain in MPTP treated mice, and Nedd4-2 maybe a potential target in regulating glutamate transporters in PD.	SIGNOR-278706
P63000	Q8IYU2	0	ubiquitination	down-regulates quantity by destabilization	0.367	The CNF1 toxin of pathogenic Escherichia coli addresses Rac1 to ubiquitin-proteasome system (UPS). We report the essential role of the tumor suppressor HACE1, a HECT-domain containing E3 ubiquitin-ligase, in the targeting of Rac1 to UPS. HACE1 binds preferentially GTP-bound Rac1 and catalyzes its polyubiquitylation	SIGNOR-255538

P17612

Q15208

1

phosphorylation

down-regulates activity

0.295

GSK-3β phosphorylated STK38 on residues S6 and T7 in vitro, depending largely on a PKA-mediated priming phosphorylation of STK38 on residues S10 and S11, respectively. Our results indicate that that GSK-3β inhibits STK38's full activation, and suggest that STK38 activation is required to prevent cell death in response to oxidative stress.

SIGNOR-276390

O95352

Q9H492

2

binding

up-regulates

0.872

Lc3-i is activated by the same atg7 involved in atg12 conjugation, transferred to atg3, a second e2-like enzyme, and finally conjugated to pe

SIGNOR-195236

Q16581

P01024

2

binding

up-regulates activity

0.734

A cDNA clone encoding the human C3a anaphylatoxin receptor (C3aR) was isolated from a pcDNAI/Amp expression library prepared from U-937 cells|The cDNA clone contained an insert of 4.3 kbp and was able to confer to transfected human HEK-293 cells the capacity to bind specifically iodinated human C3a.

SIGNOR-263451

P52803

P54764

2

binding

up-regulates

0.945

Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor

SIGNOR-52473

P54274

Q13315

0

phosphorylation

up-regulates activity

0.571

Telomeric protein pin2/trf1 as an important atm target in response to double strand dna breaks. activated atm directly phosphorylated pin2/trf1 preferentially on the conserved ser(219)-gln site in vitro and in vivo.

SIGNOR-108419

Q9C0A6

Q16695

1

methylation

up-regulates activity

0.2

SETD5 Exhibits Intrinsic Methyltransferase Activity on H3K36. This assay showed that SETD5 has specific histone methyltransferase activity toward K36 but not for other residues such as K4 and K27 (Figure 8B). we revealed that SETD5 is endowed with H3K36 methyltransferase, which is necessary for RNA elongation and processing and, ultimately, correct gene transcription.

SIGNOR-264621

Q13043

O95835

1

phosphorylation

up-regulates

0.623

We show that Mst2 and hWW45 interact with each other in human cells and that both Mst2 and Mst1 are able to phosphorylate Lats1 and Lats2, thereby stimulating Lats kinase activity.

SIGNOR-133551

Q9H2X6

P26367

1

phosphorylation

up-regulates activity

0.463

HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300. Mass spectrometric analysis identified three Pax6 phosphorylation sites as threonines 281, 304, and 373.

SIGNOR-251271

P33076

P42224

0

transcriptional regulation

up-regulates

0.539

When IFN-γ binds to its receptor, the receptor-associated protein tyrosine kinases Janus kinase I (JAK1) and JAK2 are activated (37). This leads to the phosphorylation of STAT1, which then dimerizes, translocates to the nucleus, and activates its target promoters, including the pIV promoter of Ciita

SIGNOR-256249

P35568

O14733

0

phosphorylation

down-regulates activity

0.369

Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223 Ser312 can be phosphorylated by kinases, such as c-jun NH2-terminal kinase and inhibitor of _B kinase

SIGNOR-217920

O43561

Q9H093

0

phosphorylation

down-regulates activity

0.2

Analysis by an in vitro kinase assay revealed that NUAK2 could phosphorylate immunoprecipitated LATS and that this phosphorylation was lost in the LATS double mutant (DM), T246A/S613A (Fig.\u00a0 xref ).|We showed that phosphorylation of Ser613, located upstream of the KD, adjacent to the MOB binding site and to a lesser extent the N-terminal localized T246, are required for NUAK2 to inhibit LATS.

SIGNOR-280052

P51812

P04637

1

phosphorylation

up-regulates activity

0.336

Here we show that ribosomal S6 kinase 2 (RSK2) activates and phosphorylates p53 (Ser15) in vitro and in vivo and colocalizes with p53 in the nucleus.

SIGNOR-279567

P42229

P60484

0

dephosphorylation

down-regulates

0.439

The forced expression of pten in the eol-1r cells dephosphorylated akt, erk and stat5 /eol-1r cells showed epigenetic silencing of the phosphatase and tensin homolog deleted on chromosome ten (pten) gene. Exposure of eol-1r cells to imatinib failed to dephosphorylate akt, erk and stat5, although pdgfr? Was effectively inactivated. The forced expression of pten negatively regulated these signal pathways and sensitized eol-1r cells to imatinib.

SIGNOR-166481

O15151

P06493

0

phosphorylation

down-regulates

0.407

Cdc2p34 phosphorylates mdmx on ser 96 in vitro. Mutation within this site (mdmx(s96a)) impairs, whereas phosphomimic substitution (mdmx(s96d)) increases the cytoplasmic localization of mdmx, suggesting that cdk2/cdc2p34 phosphorylation is required for export of mdmx from the nucleus

SIGNOR-134388

O14965

Q9Y6A5

1

phosphorylation

up-regulates activity

0.937

We show that this conserved serine on human TACC3 (Ser(558)) is also phosphorylated by Aurora A. Moreover, phosphorylation of TACC3 by Aurora A in human cells is essential for its proper localization to centrosomes and proximal mitotic spindles. Inhibition of Aurora A with the selective small molecule inhibitor MLN8054 in cultured human tumor cells resulted in mislocalization of TACC3 away from mitotic spindles in a concentration-dependent manner.

SIGNOR-262655

Q13501

P46934

0

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

Q9UQD0

P0DP24

2

binding

down-regulates activity

0.45

Here we show that calmodulin (CaM), a ubiquitous Ca2+-sensing protein, binds to the carboxy-terminal 'IQ' domain of the human cardiac Na channel (hH1) in a Ca2+-dependent manner. This binding interaction significantly enhances slow inactivation-a channel-gating process linked to life-threatening idiopathic ventricular arrhythmias.

SIGNOR-266330

Q6PKX4

P07949

2

binding

up-regulates

0.647

These data identify dok-6 as a novel dok-4/5-related adaptor molecule that may function in vivo to transduce signals that regulate ret-mediated processes such as axonal projection.

SIGNOR-127382

Q86Y01

Q09472

2

binding

up-regulates

0.381

We found that a significant fraction of dtx1 proteins were localized in the nucleus and physically interacted with the transcriptional coactivator p300.

SIGNOR-110629

P08183

O94952

2

binding

down-regulates quantity by destabilization

0.325

Here we demonstrate that a ubiquitin E3-ligase, FBXO21, targets the multidrug resistance transporter, ABCB1, also known as P-glycoprotein (P-gp), for proteasomal degradation.Purified in vitro translated FLAG-tagged P-gp along with E2 (UbcH5c), E3 ligase FBXO21, Cul1, Skp1, Roc1 purified from Sf-9 insect cells were incubated in vitro.

SIGNOR-272422

Q14344

P25116

2

binding

up-regulates

0.599

The protease-activated receptors (PAR)2 are a class of G protein-coupled receptors (GPCR) that are activated by the proteolysis of the N-terminal exodomain. Upon proteolysis, the newly formed n terminus acts as a tethered ligand that activates the receptor and initiates signaling cascades through multiple g proteins (galfaq, galfai, and galfa12/13).

SIGNOR-196006

Q13315

Q9Y6D9

1

phosphorylation

up-regulates activity

0.2

ATM mediated Mad1 Serine 214 phosphorylation regulates Mad1 dimerization and the spindle assembly checkpoint.|Together, these findings reveal an important role of ATM-mediated Mad1 Serine 214 phosphorylation in mitosis.

SIGNOR-278467

Q15058

O43663

2

binding

up-regulates activity

0.634

KIF14 interacts with PRC1 and citron kinase. We find that KIF14 targets to the central spindle via its interaction with PRC1 and has an essential function in cytokinesis. I

SIGNOR-266423

O14843

P08754

2

binding

up-regulates activity

0.2

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

SIGNOR-256821

Q9BRS8

P08670

2

binding

up-regulates activity

0.271

Interaction of LARP6 with vimentin.Here, we report that vimentin filaments associate with collagen mRNAs in a 5'SL- and LARP6-dependent manner and stabilize collagen mRNAs. LARP6 interacts with vimentin filaments through its La domain and colocalizes with the filaments in vivo.

SIGNOR-277624

O60603

P58753

2

binding

up-regulates activity

0.726

To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group

SIGNOR-266745

P68400

P27540

1

phosphorylation

down-regulates

0.34

Here, we show that arnt and alt arnt proteins are differentially phosphorylated by protein kinase ckii in vitro. Phosphorylation had an inhibitory effect on dna-binding to an e-box probe by alt arnt, but not arnt, homodimers. This inhibitory phosphorylation occurs through ser77.

SIGNOR-140034

P28360

P56178

2

binding

down-regulates activity

0.389

We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities.

SIGNOR-240987

P31749

Q96HP0

1

phosphorylation

up-regulates activity

0.372

Akt and PP2A reciprocally regulate the guanine nucleotide exchange factor Dock6 to control axon growth of sensory neurons|At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser(1194). | In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, whereas reintroduction of Dock6 with a phosphomimetic S1194E mutation resulted in premature branching

SIGNOR-275666

P50542

Q13315

0

phosphorylation

up-regulates activity

0.497

Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor protein p62, directing the autophagosome to peroxisomes to induce pexophagy.

SIGNOR-262792

Q13950

P46937

2

binding

down-regulates

0.449

Here we show that the endogenous yes-associated protein (yap), a mediator of src/yes signaling, interacts with the native runx2 protein, an osteoblast-related transcription factor, and suppresses runx2 transcriptional activity in a dose-dependent manner.

SIGNOR-195221

P35813

O15169

1

dephosphorylation

down-regulates

0.435

Pp2c utilizes axin as a substrate both in vitro and in vivo and decreases its half-life. These results indicate that pp2c is a positive regulator of wnt signal transduction and mediates its effects through the dephosphorylation of axin.

SIGNOR-74231

P49840

Q6R327

1

phosphorylation

down-regulates quantity by destabilization

0.387

We show that this process is dependent on glycogen synthase kinase 3 (GSK3): GSK3 was associated with rictor and directly phosphorylated the Thr-1695 site in a putative CDC4 phospho-degron motif of rictor; mutation of this site impaired the interaction between rictor and FBXW7, decreased rictor ubiquitination, and increased rictor stability.

SIGNOR-276899

P45983

Q9NR28

1

phosphorylation

up-regulates activity

0.371

JNK1\u2011mediated phosphorylation of Smac/DIABLO at the serine 6 residue is functionally linked to its mitochondrial release during TNF\u2011\u03b1-\u2011induced apoptosis of HeLa cells.

SIGNOR-280029

P00519

Q12923

0

dephosphorylation

down-regulates activity

0.39

We also found that PTPN13 dephosphorylates and inhibits c-Abl.|While the above results indicated that calpain-2 could cleave PTPN13 and that PTPN13 could dephosphorylate c-Abl at tyrosine 245, they did not determine whether calpain-2-mediated cleavage of PTPN13 resulted in its inactivation and increased tyrosine phosphorylation of c-Abl at tyrosine 245.

SIGNOR-277012

P15172

P30281

1

transcriptional regulation

up-regulates quantity by expression

0.374

Here we report that, at the onset of differentiation, activation by MyoD of the Rb, p21, and cyclin D3 genes occurs in the absence of new protein synthesis and with the requirement of the p300 transcriptional coactivator.

SIGNOR-238526

Q13131

P60891

1

phosphorylation

down-regulates activity

0.2

We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production.

SIGNOR-265729

O00470

P31269

2

binding

up-regulates activity

0.62

We now show that the Hoxa-9 protein physically interacts with Meis1 proteins. Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.

SIGNOR-241162

Q14938

P55317

2

binding

up-regulates

0.335

Androgen receptor (ar) action throughout prostate development and in maintenance of the prostatic epithelium is partly controlled by interactions between ar and forkhead box (fox) transcription factors, particularly foxa1./ Foxa1 is capable of bringing ar and nfix into proximity, indicating that foxa1 facilitates the ar and nfi interaction by bridging the complex.

SIGNOR-205082

P46934

Q96NT3

1

polyubiquitination

down-regulates quantity by destabilization

0.419

The E3 ligase NEDD4 regulates GUCD1 degradation. many polyubiquitinylated species of GUCD1 appeared as high molecular weight forms, suggesting that GUCD1 is degraded by the proteasome, after polyubiquitin chain formation, in the presence of NEDD4-1.

SIGNOR-272846

P23443

Q92519

1

phosphorylation

down-regulates quantity by destabilization

0.356

Furthermore, Smurf1-mediated ubiquitination required phosphorylation of TRIB2 by p70 S6 kinase (p70S6K) via another domain (amino acids 69-85) that is also essential for correct TRIB2 subcellular localization. Mutation of Ser-83 diminished p70S6K-induced phosphorylation of TRIB2.

SIGNOR-275433

P12931

P51692

1

phosphorylation

up-regulates

0.578

Stat5 is activated by a broad spectrum of cytokines, as well as non-receptor tyrosine kinases, such as src. these conformational differences may in part be due to differential effects of prl and src on stat5b tyrosine phosphorylation, since src induced several additional sites of tyrosine phosphorylation of stat5b at residues other than tyr-699, including tyr-724 and tyr-679.

SIGNOR-99002

O43432

Q6P2M8

0

phosphorylation

up-regulates

0.2

Here we report that activity-dependent translational initiation in cultured rat hippocampal neurons is enhanced by camki-mediated phosphorylation of ser1156 in eukaryotic initiation factor eif4gii (4gii).

SIGNOR-197190

P49841

P35568

1

phosphorylation

down-regulates quantity by destabilization

0.454

HG activates GSK3beta, which phosphorylates IRS1 at serine 332, leading to the ubiquitination and proteasome mediated degradation of IRS1.

SIGNOR-279183

P01019-PRO_0000032457

Q9BYF1

2

binding

up-regulates activity

0.2

At first, ACE2 has been demonstrated to induce conversion of Ang I into Ang (1–7) by means of intermediate production of Ang (1–9), a fragment with unknown function.

SIGNOR-260226

P00441

O96017

0

phosphorylation

up-regulates activity

0.376

ROS signaling is mediated by Mec1/ATM and its effector Dun1/Cds1 kinase, through Dun1 interaction with Sod1 and regulation of Sod1 by phosphorylation at S60, 99. In the nucleus, Sod1 binds to the promoters and regulates the expression of oxidative resistance and repair genes.

SIGNOR-262794

P46527

P31749

0

phosphorylation

down-regulates

0.85

Because Thr198-phosphorylated p27Kip1 was localized only in the cytoplasm, Akt might promote 14-3-3 binding to p27Kip1 by phosphorylation at Thr198, allowing its cytoplasmic localization and degradation.

SIGNOR-88294

P06213

Q14449

2

binding

down-regulates activity

0.761

Growth factor receptor-bound protein 14 (Grb14) interacts with insulin receptor (IR) through the between PH and SH2 (BPS) domain. Grb14-IR complex formation is initiated by insulin stimulation, and the binding event results in the inhibition of insulin signalling.

SIGNOR-264873

P17861

2

binding

up-regulates activity

0.2

E4BP4, ATF-6, OASIS, and XBP-1 all formed strong homodimeric associations on the array Transcription factor dimerization can increase the selectivity of protein-DNA interactions and generate a large amount of DNA binding diversity from a relatively small number of proteins

SIGNOR-224199

Q9GZV5

Q06710

2

binding

up-regulates

0.303

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

SIGNOR-182253

P20042

Q9NR50

0

guanine nucleotide exchange factor

up-regulates activity

0.848

EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.

SIGNOR-269131

Q12834

Q16763

2

binding

up-regulates activity

0.872

Ube2S depends on the cell cycle-dependent association with the APC/C activators Cdc20 and Cdh1 for its activity

SIGNOR-265082

P23443

P62753

1

phosphorylation

up-regulates activity

0.937

A knockin mouse carrying mutations at all phosphorylation sites in the primary s6k substrate, ribosomal protein s6 (rps6), has provided insight into the physiological role of this protein phosphorylation event. Of the many known substrates of s6k1, it is rps6 that has been shown to be directly involved, via its phosphorylation, in controlling cell size.

SIGNOR-135176

Q8WW43

Q92542

2

binding

up-regulates

0.94

By using co-immunoprecipitation and nickel affinity pull-down approaches, we now show that mammalian aph-1 (maph-1), a conserved multipass membrane protein, physically associates with nicastrin and the heterodimers of the presenilin amino- and carboxyl-terminal fragments in human cell lines and in rat brain.These data indicate that maph-1 is probably a functional component of the gamma-secretase complex

SIGNOR-93307

P30411

Q03113

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-257344

P15391

P20023

2

binding

up-regulates activity

0.783

Complement receptor type 2 (CR2)/CD21 plays a key role in the development of high-affinity Abs and long-lasting memory to foreign Ags. When CR2 is bound by its primary C3 activation fragment–derived ligand, designated C3d, it coassociates with CD19 on B cells to amplify BCR signaling.

SIGNOR-266642

O95967

P15502

2

binding

up-regulates activity

0.557

Fibulin-4 directly binds LOX, and this interaction enhances fibulin-4 binding to tropoelastin, thus forming a ternary complex that may be critical for elastin cross-linking.

SIGNOR-252136

P46527

O15297

0

dephosphorylation

down-regulates activity

0.259

Increased expression of wildtype WIP1 reduces stability of p27 Kip1 while increased expression of similar amounts of phosphatase-dead WIP1 has no effect on p27 Kip1 protein stability.|We demonstrate that wildtype, but not phosphatase-dead WIP1, efficiently dephosphorylates p27 Kip1 Ser140 both in vitro and in cells and that this dephosphorylation is sensitive to the WIP1 specific inhibitor GSK 2830371.

SIGNOR-277109

O95319

P12931

0

phosphorylation

up-regulates activity

0.321

Site-directed mutagenesis of putative tyrosine phosphorylation sites in CUGBP2 identified tyrosine 39 as a c-Src target, and a CUGBP2 with a mutated tyrosine 39 displayed an attenuated ability to bind COX-2 mRNA.

SIGNOR-263195

P28347

P46937

2

binding

up-regulates

0.905

When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead14.

SIGNOR-201465

Q13315

Q9H7Z6

1

phosphorylation

up-regulates activity

0.469

In this study we present evidence that MOF is phosphorylated at the threonine 392 residue (pT392-MOF) by ATM subsequent to IR induced DNA damage.|Interestingly, ATM dependent-MOF phosphorylation increases MOF retention on DNA post-irradiation in S/G2-phase cells.

SIGNOR-278350

Q8NFZ3

Q9Y4C0

2

binding

up-regulates activity

0.2

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264163

Q86T96

O95409

1

ubiquitination

down-regulates quantity by destabilization

0.374

Rinescan directly interact with Zic2. the ubiquitination of endogenous Zic2 was enhanced by Myc-Rines in rat neural stem cellline MNS70 cells. Rines-induced degradation of Zic2

SIGNOR-226303

P63096

P12931

2

binding

up-regulates activity

0.486

Here we demonstrate that Galphas and Galphai, but neither Galphaq, Galpha12 nor Gbetay, directly stimulate the kinase activity of downregulated c-Src

SIGNOR-256526

Q15208

Q96QF0

1

phosphorylation

up-regulates activity

0.366

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

SIGNOR-263036

O14874

P12931

0

phosphorylation

up-regulates activity

0.2

Src phosphorylated BCKDK at the tyrosine 246 (Y246) site in vitro and ex vivo. Knockdown and knockout of Src downregulated the phosphorylation of BCKDK. Importantly, phosphorylation of BCKDK by Src enhanced the activity and stability of BCKDK, thereby promoting the migration, invasion, and EMT of CRC cells.

SIGNOR-275583

P29350

Q12809

1

dephosphorylation

down-regulates

0.2

Our results show that erg-1 is a shp-1 substrate constituting the first report that an ion current is regulated by shp-1.

SIGNOR-94007

P48730

P17302

1

phosphorylation

up-regulates activity

0.6

We have examined the role of casein kinase 1 (CK1) in connexin-43 (Cx43) gap junction assembly. Cellular co-immunoprecipitation experiments and in vitro CK1 phosphorylation reactions indicate that CK1 interacted with and phosphorylated Cx43, initially on serine(s) 325, 328, or 330.| To examine CK1 function, normal rat kidney cells were treated with CKI-7, and Cx43 content was analyzed by Triton X-100 extraction, cell-surface biotinylation, and immunofluorescence. Western blot analysis indicated a slight increase in total Cx43, whereas gap junctional (Triton-insoluble) Cx43 decreased, and non-junctional plasma membrane Cx43 increased (as detected by cell surface biotinylation).

SIGNOR-249331

P11142

O95817

2

binding

up-regulates activity

0.788

Heat shock cognate protein 70 (Hsc70) regulates protein homeostasis through its reversible interactions with client proteins. Hsc70 has two major domains: a nucleotide-binding domain (NBD), that hydrolyzes ATP, and a substrate-binding domain (SBD), where clients are bound. Members of the BAG family of co-chaperones, including Bag1 and Bag3, are known to accelerate release of both ADP and client from Hsc70.

SIGNOR-254116

O60346

P05771

1

dephosphorylation

down-regulates quantity

0.341

Here we show that the two PHLPP isoforms, PHLPP1 and PHLPP2, also dephosphorylate the hydrophobic motif on PKC betaII, an event that shunts PKC to the detergent-insoluble fraction, effectively terminating its life cycle

SIGNOR-237047

P49715

P35712

0

transcriptional regulation

up-regulates quantity by expression

0.292

We found that SOX6 regulates adipogenesis in vertebrate species by activating adipogenic regulators including PPARγ, C/EBPα and MEST

SIGNOR-255824

O76070

P25098

0

phosphorylation

down-regulates activity

0.2

GRK-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and PLD2. Mutation of Ser124 dramatically inhibits γ-synuclein phosphorylation by GRK2

SIGNOR-251204

P41279

P36507

1

phosphorylation

up-regulates

0.436

Cot proteins were used in an in vitro kinase assay using mek as a substrate. Samples were analyzed by western blotting. As seen in the cascade activity assay only wild-type cot was active against mekregulation of cot is of great interest to the signaling field since the cot/mek/erk pathway potentially plays a role in the etiology of inflammatory autoimmune diseases.

SIGNOR-129694

Q7L2Z9

P53350

0

phosphorylation

down-regulates quantity by destabilization

0.588

Notably, although Plk1 did not alter the level of PBIP1 and CENP-Q ubiquitination, Plk1-dependent phosphorylation and delocalization of these proteins from kinetochores appeared to indirectly lead to their degradation in the cytosol. From these analyses, we identified nine CENP-Q residues (Thr-123, Thr-135, Ser-138, Ser-139, Ser-248, Ser-249, Ser-253, Ser-255, and Thr-256) that were phosphorylated in both in vitro and in vivo samples (Fig. 4B), suggesting that Plk1 phosphorylates these sites.

SIGNOR-265227

Q15208

Q9BX46

1

phosphorylation

up-regulates activity

0.355

Phosphorylation of Rbm24 by Stk38 is crucial for the maintenance of cardiac sarcomeric gene expression in cardiac cells.|These results indicated that Stk38 increases Rbm24 protein stability probably by interfering with the ubiquitin-proteasome protein degradation pathway.

SIGNOR-278291

Q13418

E9PAV3

1

phosphorylation

up-regulates

0.426

The inactivation of gsk3? In response to adhesion and ilk activation (6) would then result in a thr-159-hypophosphorylated ?-Nac that would become unavailable for proteasome degradation but would become a substrate for the ilk kinase activity on residue ser-43. The ser-43-phosphorylated ?-Nac would preferentially interact with c-jun (30), translocate to the nucleus, and potentiate transcription

SIGNOR-127631

P51812

P03372

1

phosphorylation

up-regulates

0.403

S6k1 regulates estrogen receptor alpha (eralpha) by phosphorylating it on serine 167, leading to transcriptional activation of eralpha.

SIGNOR-182958

Q13309

Q8WWM9

2

binding

down-regulates quantity by destabilization

0.2

Skp2 induces ubiquitin-dependent degradation of Cygb. To this end, we performed an in vivo ubiquitination assay in HEK293T cells by transfecting relevant plasmids as indicated. The V5-Skp2DN was generated by deleting the N-terminal residues from 1 to 153 containing the F-box domain, which is involved in recruiting Skp2 to the SCF complex.

SIGNOR-272792

P25942

P29965

2

binding

up-regulates activity

0.929

Ramos cells were mixed with increasing numbers of transfected cells that expressed cd70 (cd27l) or cd154 (cd40l), both of which are expressed by activated T cells, in the presence of anti-igm ab. Cd27 ligation as well as cd40 ligation inhibited bcr-mediated apoptosis in a dose-dependent manner. cd40 binds its ligand cd40l.

SIGNOR-93432

P46663

P38405

2

binding

up-regulates activity

0.25

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

SIGNOR-256907

P24941

Q16204

1

phosphorylation

up-regulates

0.2

Serine 244 phosphorylation is required for h4 apoptotic function.

SIGNOR-121198

P48729

Q13158

1

phosphorylation

down-regulates activity

0.333

FADD is essential for death receptor (DR)-induced apoptosis.|Phosphorylation of FADD at serine 194 by CKIalpha regulates its nonapoptotic activities

SIGNOR-139307

P78371

Q15418

0

phosphorylation

up-regulates

0.249

Furthermore, both the s260a and s260d mutants showed a decreased folding capacity as compared to cells expressing the wild-type cct_ subunit ( fig.?_5e), suggesting that a cyclic phosphorylation of the s260 site by s6k1 is likely to be important for chaperonin function and that mutation of this site interferes with this process.

SIGNOR-172986

Q8TEK3

O75592

1

transcriptional regulation

down-regulates quantity by repression

0.2

Overexpression of DOT1L decreased the expression of HECTD4 and MYCBP2 in LNCaP, C42B, and 22rv1 cells (Supplementary Fig. 5c), suggesting that DOT1L plays a role in repressing these targets either directly or indirectly.

SIGNOR-267151

P08631

2

phosphorylation

up-regulates activity

0.2

Hck transiently expressed in human embryonic kidney 293T cells was found to be phosphorylated at Tyr-29 and Tyr-388, proving that Hck can also undergo autophosphorylation at both sites in vivo. autophosphorylation of Tyr-29 contributes significantly to the activation of Hck.

SIGNOR-251266

P16410

P06239

0

phosphorylation

up-regulates quantity by stabilization

0.749

Lck and Fyn, but not ZAP70, induce tyrosine phosphorylation of CTLA-4 in the cell line HEK293. Phosphorylation of CTLA-4 occurs on both Y201 and Y218. Phosphorylation of Y201 correlated with accumulation of CTLA-4 on the cell surface.

SIGNOR-251370

O95466

Q05655

0

phosphorylation

up-regulates activity

0.27

PKC\u03b4 induces FMNL1 phosphorylation.

SIGNOR-279261

P06239

P15941

1

phosphorylation

up-regulates activity

0.46

The present results demonstrate that Lck phosphorylation of MUC1 on Y-46 also increases binding of MUC1 and beta-catenin. The results further show that ZAP-70 phosphorylation of MUC1-CD stimulates the interaction of MUC1 and beta-catenin

SIGNOR-249358

P68871

O95600

0

transcriptional regulation

down-regulates quantity by repression

0.2

These results establish KLF8 as a CACCC-box binding protein that associates with CtBP and represses transcription.

SIGNOR-266052

Q9NR19

P08236

1

transcriptional regulation

up-regulates quantity by expression

0.262

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

SIGNOR-276554

Q15746

P12931

0

phosphorylation

up-regulates

0.417

Ec mlck-1 is phosphorylated by p60(src) on tyr(464) and tyr(471), resulting in a 2- to 3-fold increase in ec mlck-1 enzymatic activity.

SIGNOR-85009

Q9NWQ8

P06241

0

phosphorylation

up-regulates activity

0.703

Thus, Fyn mediates Csk-binding protein-Csk interaction and recruits Csk to rafts by phosphorylating Csk-binding protein.

SIGNOR-279987

P05231

O95644

0

transcriptional regulation

up-regulates quantity by expression

0.415

The calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway has been found to play a role in regulating growth and differentiation in several cell types. However, the functional significance of NFAT in the vasculature is largely unclear. Here we show that NFATc1, NFATc3, and NFATc4 are expressed in human myometrial arteries. |Chronic inhibition of NFAT significantly reduced IL-6 production in intact myometrial arteries and inhibited cell proliferation in vascular smooth muscle cells cultured from explants from the same arteries.

SIGNOR-251730

Q13555

Q4G163

1

phosphorylation

down-regulates activity

0.2

Activated CaMKII and polo-like kinase simultaneously phosphorylate and inactivate Emi2 [ xref , xref , xref , xref , xref ]).

SIGNOR-280200

Q7Z3K3

P45973

2

binding

down-regulates activity

0.433

POGZ was found to bind to HP1alpha through a zinc-finger-like motif. Binding by POGZ, mediated through its zinc-finger-like motif, competed with PxVxL proteins and destabilized the HP1alpha-chromatin interaction.

SIGNOR-264487

Q92574

P54646

0

phosphorylation

up-regulates

0.551

Under energy starvation conditions, the amp-activated protein kinase (ampk) phosphorylates tsc2 and enhances its activity.

SIGNOR-119541

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

P16519

P01178-PRO_0000020495

1

cleavage

up-regulates quantity

0.2

Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.

SIGNOR-270335

Q96PU5

P43004

1

ubiquitination

down-regulates quantity

0.304

Our results confirm that Nedd4-2 knockdown in MPTP treated mice increased GLT-1 expression at the membrane protein level (XREF_FIG; P < 0.01).|These results suggest that Nedd4-2 mediates the ubiquitination of both GLT-1 and GLAST in the midbrain in MPTP treated mice, and Nedd4-2 maybe a potential target in regulating glutamate transporters in PD.

SIGNOR-278706

P63000

Q8IYU2

0

ubiquitination

down-regulates quantity by destabilization

0.367

The CNF1 toxin of pathogenic Escherichia coli addresses Rac1 to ubiquitin-proteasome system (UPS). We report the essential role of the tumor suppressor HACE1, a HECT-domain containing E3 ubiquitin-ligase, in the targeting of Rac1 to UPS. HACE1 binds preferentially GTP-bound Rac1 and catalyzes its polyubiquitylation

SIGNOR-255538