GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P10451	P08254	0	cleavage	up-regulates activity	0.67	In this study, we found a novel motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved mouse OPN binds to α9β1 integrin. Importantly, this novel motif is involved in the development of anti-type II collagen antibody-induced arthritis (CAIA). This study provides the first in vitro and in vivo evidence that OPN cleavage by MMP-3/7 is an important regulatory mechanism for CAIA.	SIGNOR-253320
Q8IVF5	P63000	1	guanine nucleotide exchange factor	up-regulates activity	0.589	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-260578
Q96GD4	Q99986	0	phosphorylation	up-regulates activity	0.429	In the VRK1 overexpression of experiment, VRK1 caused a significant stabilization of AURKB, with no change in level after 24h, which is consistent with protection of AURKB against its known degradation by ubiquitylation .\|The phosphorylation of AURKB by VRK1 and VRK1 by AURKB was tested using a kinase-dead form as substrate.	SIGNOR-280160
Q8TDX7	Q15058	1	phosphorylation	up-regulates activity	0.371	Nek7 direct phosphorylation is required for the anaphase localization of Kif14. we generated an EGFP-Kif14-5A construct in which Ser56, Ser607, Ser1217, Ser1219, and Ser1220 were all mutated to Ala. When transfected into HeLa cells, EGFP-Kif14-5A was expressed to similar levels as WT Kif14 (Fig. S3 C), but its localization to the central spindle in anaphase cells was completely abolished (Fig. 6 C).	SIGNOR-266420
Q08209	Q969Q1	0	ubiquitination	down-regulates quantity	0.26	First, downregulation of MuRF1 significantly attenuates degradation of CnA in cardiomyocytes in vitro, indicating that endogenous MuRF1 negatively regulates the stability of CnA in a cell-autonomous manner.\|Furthermore, MuRF1 directly ubiquitinated CnA in vitro.\|These results suggest that MuRF1 directly polyubiquitinates CnA.	SIGNOR-278736
P19838	O15111	0	phosphorylation	down-regulates quantity by destabilization	0.747	All residues of p105 phosphorylated by ikka are c-terminal; the major phosphorylation region contains three serines (ser923; ser927;ser932) and two threonines (thr927 and thr391).	SIGNOR-70449
Q12947	Q9H1B7	1	transcriptional regulation	up-regulates quantity by expression	0.253	FOXF2 directly bound the promoter of E3 ligase interferon regulatory factor 2-binding protein-like (IRF2BPL) and induced its transcriptional expression. IRF2BPL in turn interacted with β-catenin, increasing its ubiquitination and degradation.	SIGNOR-267152
P42772	Q00532	0	phosphorylation	up-regulates activity	0.2	We demonstrated that depletion of CDKL1 notably upregulated the protein expression of P15. P15 is shown to be a target of CDKL1 in CRC, either direct or indirect.	SIGNOR-273862
P48729	Q9H6E5	1	phosphorylation	up-regulates activity	0.267	We identified a phosphorylated residue (serine 6, S6) on Star-PAP in the zinc finger region, the domain required for PIPKIα interaction. We show that S6 is phosphorylated by CKIα within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIα.	SIGNOR-273619
Q13009	Q15835	0	phosphorylation	down-regulates activity	0.2	For example, RhoK phosphorylates and inhibits TIAM1, STEF, and PAR3; disrupts the polarity complex; and prevents Rac activation ( xref ).	SIGNOR-279995
P11388	P05771	0	phosphorylation	up-regulates activity	0.359	Here, we have shown that the enzymatic activity of topoisomerase II alpha protein purified from HeLa cell nuclei was strongly enhanced following phosphorylation by protein kinase C. \| Site-directed mutagenesis studies indicated that phosphorylation of serine 29 generated both of these phosphopeptides.	SIGNOR-249195
Q05655	Q14247	1	phosphorylation	up-regulates activity	0.246	Together these findings demonstrate that phosphorylation of cortactin on S405 and S418 residues is required for its interaction with WAVE2 in MCP1-induced cytoskeleton remodeling, facilitating HASMC migration. In addition, the MCP1-induced cortactin phosp	SIGNOR-260890
P17612	P23677	1	phosphorylation	up-regulates activity	0.327	Two isoforms of the inositol 1,4,5-trisphosphate 3-kinase have been identified, the A form and the B form. phosphorylation of isoform A by the cyclic AMP-dependent protein kinase increased activity 1.5-fold, whereas phosphorylation of isoform B decreased activity by 45%. major phosphorylation sites in the protein are Ser119 for PKA. Ser119 in the A isoform is conserved in the B isoform as Ser328	SIGNOR-249994
P30307	Q8TDC3	0	phosphorylation	down-regulates	0.483	Overexpression of hssad1 resulted in an increased phosphorylation of cdc25c on ser-216 in vivo.Phosphorylation of cdc25 triggers cell-cycle arrest by the sequestration of cdc25 by 14-3-3	SIGNOR-56473
P24588	P48454	1	relocalization	up-regulates activity	0.262	Using a viral-mediated molecular replacement strategy in rat hippocampal slices, we found that AKAP is required for NMDA receptor-dependent long-term depression solely because of its interaction with calcineurin	SIGNOR-261291
Q92630	Q00987	0	ubiquitination	down-regulates quantity by destabilization	0.57	Under normal conditions, nuclear and not cytoplasmic DYRK2 is ubiquitinated by MDM2, resulting in its constitutive degradation.\|Upon exposure to genotoxic stress, ATM phosphorylates DYRK2 at Thr-33 and Ser-369, which enables DYRK2 to escape from degradation by dissociation from MDM2 and to induce the kinase activity toward p53 at Ser-46 in the nucleus.	SIGNOR-275579
P15056	P00519	1	phosphorylation	up-regulates activity	0.275	BRAF V600E activates Abl and Arg.\|Rather, BRAF V600E, a serine threonine kinase, induced Abl threonine phosphorylation (XREF_FIG), and tyrosine phosphorylation of kinase-inactive Abl or Arg, which lack the ability to autophosphorylate (XREF_FIG).	SIGNOR-278914
P17252	P49840	1	phosphorylation	down-regulates	0.345	Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.	SIGNOR-115714
Q8TAU0	Q13477	1	transcriptional regulation	up-regulates quantity by expression	0.428	We provide evidence that NKX2.3 can activate MAdCAM-1 transcription directly	SIGNOR-266219
P17252	Q96AX2	1	phosphorylation	down-regulates activity	0.2	We also show that Rab37 is phosphorylated by protein kinase Cα (PKCα) at threonine 172 (T172), leading to attenuation of its GTP-bound state, and impairment of the Rab37-mediated exocytosis of TIMP1, and thus reduces its suppression activity on lung cancer cell motility.	SIGNOR-273803
Q13233	Q13158	1	phosphorylation	down-regulates activity	0.503	The results clearly show that fadd phosphorylation at ser194 affects functions both upstream and downstream of the mekk1/mkk7/jnk1 pathway and is closely associated with chemosensitivity in prostate cancer cells	SIGNOR-123168
Q9H4B4	Q99986	1	phosphorylation	up-regulates	0.474	Vrk1 does not phosphorylate plk3, but plk3 phosphorylates the c-terminal region of vrk1 in ser342. Vrk1 with substitutions in s342 is catalytically active but blocks golgi fragmentation, indicating that its specific phosphorylation is necessary for this process.	SIGNOR-182858
P49810	P48730	0	phosphorylation	up-regulates activity	0.364	In vitro the large hydrophilic loop of PS-2 between transmembrane domains 6 and 7 can be phosphorylated by casein kinase-1 (CK-1) and CK-2, but not by PKA or PKC. Quantitative analysis of in vitro phosphorylation demonstrates the presence of two phosphorylation sites for CK-1 and a single site for CK-2. A deletion analysis revealed that the CTF of PS-2 is phosphorylated in vivo within an acidic sequence containing three potential phosphorylation sites for CKs (serines 327, 330, and 335). These data suggest that CK type protein kinases phosphorylate the CTF of PS-2 within its hydrophilic loop domain in vivo. Interestingly, the potential phosphorylation sites are located directly adjacent to the recently identified caspase cleavage sites.	SIGNOR-250802
P06241	Q96J84	1	phosphorylation	up-regulates activity	0.2	Here we have characterized Neph1, another SD component, as a novel substrate of SFK. Fyn interacts with and phosphorylates the cytoplasmic domain of Neph1 in vitro and in intact cells. Both tyrosine 637 and 638 of Neph1 are crucial for Neph1-Grb2 binding.	SIGNOR-262746
P29590	P28482	0	phosphorylation	up-regulates	0.359	We report here that as(2)o(3) treatment induces phosphorylation of the pml protein through a mitogen-activated protein (map) kinase pathway. Increased pml phosphorylation is associated with increased sumoylation of pml and increased pml-mediated apoptosis.	SIGNOR-124248
P25116	P07384	0	cleavage	up-regulates activity	0.376	PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases \| The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II\|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.\|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.\|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus	SIGNOR-263559
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
Q9NS28	Q13976	0	phosphorylation	up-regulates activity	0.332	Cyclic AMP- and cyclic GMP-dependent kinases (PKA, PKG) inhibit the interaction of RGS18 and 14-3-3 by phosphorylating S216. S216 phosphorylation might activate PP1 leading to dephosphorylation of both 14-3-3 binding sites, S49 and S218, and detachment of 14-3-3. Removal of 14-3-3 activates RGS18 to turn off Gq signaling thus contributing to platelet inhibition.	SIGNOR-273785
P17676	Q15418	0	phosphorylation	up-regulates activity	0.683	13 The data presented support previous findings that C/EBPbeta can be a molecular target of RSK1, 16 but provide the first indication that RSK1 can phosphorylate and activate C/EBPbeta to mediate the IL-6 signalling events in cholangiocarcinoma.\|As mentioned above, RSK1 has been shown to activate C/EBPbeta in hepatic stellate cells in an experimental model of liver fibrosis.	SIGNOR-280112
P78563	Q05513	0	phosphorylation	up-regulates activity	0.2	Here, we identified ADAR2 as a direct substrate of PKCζ in CRC cells. Phosphorylation of ADAR2 regulates its editing activity, which is required to maintain miR-200 steady-state levels, suggesting that the PKCζ/ADAR2 axis regulates miR-200 secretion through RNA editing.	SIGNOR-277391
Q00987	P08069	1	ubiquitination	down-regulates quantity by destabilization	0.66	We could prove that Mdm2 physically associates with IGF-1R and that Mdm2 causes IGF-1R ubiquitination in an in vitro assay.	SIGNOR-278571
Q969W9	P49910	0	transcriptional regulation	down-regulates quantity by repression	0.271	ZNF165 drives the unrestrained activation of transforming growth factor β (TGFβ) signalling by directly inactivating the expression of negative feedback pathway regulators, SMURF2, SMAD7 and PMEPA1.	SIGNOR-266094
O14965	O15350	1	phosphorylation	down-regulates activity	0.449	Aurora-A inhibits p73 and p53 transactivation functions through a common molecular mechanism.\|We report that Aurora-A phosphorylation of p73 at serine235 abrogates its transactivation function and causes cytoplasmic sequestration in a complex with the chaperon protein mortalin.	SIGNOR-278263
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
O15379	Q9UHD2	0	phosphorylation	up-regulates activity	0.2	The feedback of activation of HDAC3 by TBK1 was able to further enhance IFN production and IFN-STAT activation.\|We found that HDAC3 could be phosphorylated by TBK1.	SIGNOR-279662
P45983	Q99640	1	phosphorylation	up-regulates	0.336	A kinase assay using gst-myt1 revealed that active jnk1 or jnk3, but not jnk2, phosphorylated myt1 in vitro.	SIGNOR-183899
O15264	Q6JBY9	1	phosphorylation	down-regulates activity	0.419	CapZIP was also phosphorylated rapidly by SAPK3/p38γ and SAPK4/p38δ, and even faster and more extensively by JNK1α1, these protein kinases phosphorylating CapZIP in vitro to >3, approx. 2 and >5 mol of phosphate/mol of protein respectively within a few minutes. Following tryptic digestion and C18 chromatography, further sites phosphorylated by JNK1α1 were identified as Ser-68, Ser-83 and Ser-216 (results not shown), and are highlighted in Figure 3.Using this antibody, we showed by immunoblotting that bacterially expressed CapZIP was phosphorylated at Ser-108 by SAPK4/p38δ, JNK1α1 and ERK2 in vitro, as well as by SAPK3/p38γ (results not shown).An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.	SIGNOR-263084
Q9UHD2	Q13137	1	phosphorylation	up-regulates activity	0.795	Furthermore, we found that TBC1D9-regulated TBK1 activation and recruitment of NDP52 and ULK1 complex to damaged mitochondria (Fig.\u00a0 xref ).\|TBK1 can phosphorylate p62, OPTN, and NDP52 to promote selective autophagy by facilitating their interaction with LC3, ubiquitin, and RAB35, respectively xref , xref , xref .	SIGNOR-280151
O14522	P06241	0	phosphorylation	down-regulates activity	0.414	Synapse formation by PTPRT was inhibited by phosphorylation of tyrosine 912 within the membrane-proximal catalytic domain of PTPRT by Fyn. This tyrosine phosphorylation reduced phosphatase activity of PTPRT	SIGNOR-275543
Q9UD71	Q00535	0	phosphorylation	up-regulates activity	0.777	We find that DARPP-32 is converted into an inhibitor of PKA when phosphorylated at threonine 75 by cyclin-dependent kinase 5 (Cdk5). Cdk5 phosphorylates DARPP-32 in vitro and in intact brain cells. Phospho-Thr 75 DARPP-32 inhibits PKA in vitro by a competitive mechanism.	SIGNOR-250671
Q9P0L0	Q14721	0	relocalization	up-regulates quantity	0.2	Confirmation that Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA knockdown, and Förster resonance energy transfer (FRET)-based assays.\|As Kv2.1 accumulates on the surface it begins to bind ER VAPs and form the large and stable membrane junctions.	SIGNOR-262122
P13569	Q13976	0	phosphorylation	up-regulates	0.506	Direct amino acid sequencing and peptide mapping of cf-2 revealed that serines 660, 700, 737, and 813 as well as serine 768, serine 795, or both were phosphorylated by pka and pkgcftr possesses a large cluster of strict dibasic consensus sites for phosphorylation by protein kinase a (pka) in the r-domain and an obligatory dependence on phosphorylation is a hallmark of cftr cl(-) channel function	SIGNOR-18249
O00444	Q8NHV4	1	phosphorylation	up-regulates activity	0.593	We found that PLK4-mediated phosphorylation of NEDD1 at its S325 amino acid residue directly promotes both NEDD1 binding to SAS-6 and recruiting SAS-6 to the centrosome. \|Collectively, our results demonstrate that PLK4-regulated NEDD1 facilitates initiation of the cartwheel assembly and of daughter centriole biogenesis in mammals.	SIGNOR-272996
P40763	Q13627	0	phosphorylation	up-regulates activity	0.265	DYRK1A overexpression promotes STAT3 activity by phosphorylating STAT3 at Ser727 and contributes to reduced neuronal production and increased astroglial generation in DS.	SIGNOR-279992
Q9UM47	P00533	0	phosphorylation	up-regulates activity	0.593	Here, we report that treatment of EGFR mutated lung cancer cell lines with erlotinib, while showing robust cell death, enriches the ALDH+ stem like cells through EGFR dependent activation of Notch3.\|We also find a kinase-dependent physical association between the Notch3 and EGFR receptors and tyrosine phosphorylation of Notch3.	SIGNOR-280002
P43629	P68400	0	phosphorylation	up-regulates quantity by stabilization	0.2	Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of Ser(394) by protein kinase C slightly suppresses KIR3DL1 inhibitory function, and reduces receptor internalization and turnover.Both CKII and PKC phosphorylate KIR3DL1 in vitro. Ser364 can be phosphorylated after phosphorylation of Ser367 by CKII. It seems that phosphorylation of 3DL1 by CK does not significantly affect receptor inhibitory function or turnover, at least in the assays that we have used so far.	SIGNOR-276077
Q96J02	P08151	1	ubiquitination	down-regulates	0.578	The consequent activation of_ itch, together with the recruitment of gli1 through direct binding with_ numb, allows gli1 to enter into the complex, resulting in gli1 ubiquitination and degradation. we demonstrate that the hedgehog transcription factor gli1 is targeted by numb for itch-dependent ubiquitination, which suppresses hedgehog signals, thus arresting growth and promoting cell differentiation	SIGNOR-150847
P62714	Q9UIC8	0	methylation	up-regulates activity	0.661	Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits \|The PP2A core enzyme was methylated by a PP2A-specific leucine carboxyl methyltransferase (LCMT1)	SIGNOR-265751
Q9Y5U4	P28324	0	transcriptional regulation	up-regulates quantity by expression	0.2	Under these conditions, a significant reduction in INSIG2 expression was only observed when SAP1a siRNA was used. These observations provide supporting evidence that SAP1a may be one of the transactivators of the human INSIG2 promoter.	SIGNOR-261592
P22681	P09619	1	polyubiquitination	down-regulates quantity by destabilization	0.629	Overexpression of wild type Cbl in NIH3T3 cells led to an enhancement of the ligand-dependent ubiquitination and subsequent degradation of the PDGFRbeta, as observed with PDGFRalpha.	SIGNOR-272549
O15111	Q9Y618	1	phosphorylation	down-regulates	0.416	Nf-kappab transcription requires ikkalpha to phosphorylate smrt on chromatin, stimulating the exchange of corepressor for coactivator complexes. Ikk directly phosphorylates smrt to stimulate nuclear export. Ikkalpha orchestrates smrt derepression, a prerequisite for nf-kappab transcription and survival.	SIGNOR-129956
Q13153	P23975	1	phosphorylation	down-regulates activity	0.2	PAK1 negatively regulates the activity of the Rho exchange factor NET1.\|Specifically, PAK1 phosphorylates NET1 on three sites in vitro : serines 152, 153, and 538.	SIGNOR-280054
P01588	Q16665	0	transcriptional regulation	up-regulates quantity by expression	0.643	Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix transcription factor that regulates hypoxia-inducible genes including the human erythropoietin (EPO) gene.	SIGNOR-253695
P12931	O14746	1	phosphorylation	down-regulates	0.418	Hydrogen peroxide triggers nuclear export of telomerase reverse transcriptase via src kinase family-dependent phosphorylation of tyrosine 707	SIGNOR-102097
P28482	P29590	1	phosphorylation	up-regulates	0.359	We report here that as(2)o(3) treatment induces phosphorylation of the pml protein through a mitogen-activated protein (map) kinase pathway. Increased pml phosphorylation is associated with increased sumoylation of pml and increased pml-mediated apoptosis.	SIGNOR-124248
Q13315	O15360	1	phosphorylation	up-regulates	0.407	The s1449a mutant failed to completely correct a variety of fa-associated phenotypes. The dna damage response is coordinated by phosphorylation events initiated by apical kinases atm (ataxia telangectasia mutated) and atr (atm and rad3-related), and atr is essential for proper fa pathway function. Serine 1449 is in a consensus atm/atr site	SIGNOR-182949
P49407	Q14940	1	relocalization	down-regulates activity	0.401	Internalization of the Na(+)/H(+) exchanger NHE5 into recycling endosomes is enhanced by the endocytic adaptor proteins beta-arrestin1 and -2, best known for their preferential recognition of ligand-activated G protein-coupled receptors (GPCRs)	SIGNOR-275505
Q9Y243	P78563	1	phosphorylation	down-regulates activity	0.2	AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively	SIGNOR-276195
Q8WUI4	P67775	0	dephosphorylation	up-regulates activity	0.317	Phosphorylation of conserved serine residues triggers association with 14-3-3 proteins and cytoplasmic relocalization of class IIa HDACs, which leads to the derepression of their target genes. \|Here we identify PP2A as a phosphatase responsible for dephosphorylating the 14-3-3 binding sites in class IIa HDACs.\|we demonstrate that PP2A constitutively dephosphorylates the class IIa member HDAC7 to control its biological functions as a regulator of T cell apoptosis and endothelial cell functions.	SIGNOR-248649
Q6EIG7	Q13191	0	ubiquitination	down-regulates quantity by destabilization	0.2	Furthermore, we found that Cbl-b, an E3 ubiquitin ligase, mediates the ubiquitination and degradation of the activated Dectin-2 and Dectin-3 to negatively regulate CLR mediated innate immune responses against fungal infections.	SIGNOR-278625
Q8IW41	O43524	1	phosphorylation	up-regulates activity	0.475	Analysis of mutant alleles of FoxO3a showed that MK5 phosphorylated FoxO3a predominantly at S215, but that mutation of four of the identified sites was required to essentially abolish phosphorylation of FoxO3a by MK5 (\u201c4A\u201d) ( Figure\u00a04 C and data not shown).\|MK5 phosphorylates and activates the transcription factor FoxO3a and potentially other FoxO factors.	SIGNOR-279469
P11413	P12931	0	phosphorylation	up-regulates activity	0.274	Here, we show that tyrosine kinase c-Src interacts with and phosphorylates G6PD at Tyr 112. This phosphorylation enhances catalytic activity of G6PD by dramatically decreasing its Km value and increasing its Kcat value for substrate glucose-6-phosphate.	SIGNOR-277550
Q13233	P46531	1	phosphorylation	down-regulates activity	0.367	As a result, MEKK1 suppresses the Notch1 intracellular domain protein stability and transcriptional activity.\|We confirmed that MEKK1 binds to Notch1 intracellular domain and phosphorylates the Notch1 intracellular domain Threonine 2512 residue.	SIGNOR-279628
Q96BN8	P0CG47	1	cleavage	up-regulates quantity	0.671	Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.	SIGNOR-270819
Q92585	P62805	1	acetylation	down-regulates activity	0.2	We speculated that maml1, in addition to recruiting p300, might directly interact with histones to facilitate histone acetylation. We had observed acetylation of the histones h3 and h4.	SIGNOR-153041
P20265	O75030	1	transcriptional regulation	up-regulates quantity by expression	0.437	We further demonstrate that BRN2 induces MITF transcription through a binding site located at 50/36 of the MITF promoter	SIGNOR-249616
P08590	P42574	0	cleavage	down-regulates quantity by destabilization	0.377	By sequencing and site-directed mutagenesis, a noncanonical cleavage site for caspase-3 was mapped to the C-terminal DFVE(135)G motif. We demonstrated that vMLC1 cleavage in failing myocardium in vivo is associated with a morphological disruption of the organized vMLC1 staining of sarcomeres, and with a reduction in myocyte contractile performance.	SIGNOR-270593
Q13363	P38398	1	transcriptional regulation	down-regulates quantity by repression	0.603	Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor with oncogenic potential. We found CtBP1 was recruited to the promoter regions of Brca1 and E-cadherin genes in breast cancer cells.	SIGNOR-259196
P00533	P0DP23	1	phosphorylation	down-regulates	0.404	Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.	SIGNOR-24778
P17813	P12931	0	phosphorylation	down-regulates quantity by destabilization	0.385	We identified epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as Src-activators that induce endoglin turnover following (612)YIY(614) phosphorylation.	SIGNOR-276654
P18146	Q9Y251	1	transcriptional regulation	up-regulates quantity by expression	0.37	Promoter CpG hypomethylation and transcription factor EGR1 hyperactivate heparanase expression in bladder cancer.	SIGNOR-254267
P36956	P49327	1	transcriptional regulation	up-regulates quantity by expression	0.495	Ultimately, both the AKT and MAPK transduction pathways regulate FASN expression through the modulation of expression of sterol regulatory element-binding protein (SREBP)-1c, which binds to regulatory elements in the FASN promoter. Proto-oncogene FBI-1 (Pokemon), a transcription factor of the bric--brac tramtrack broad complex/pox viruses and zinc fingers (BTB/POZ) domain family, interacts directly with SREBP-1c through its DNA-binding domain to synergistically activate the transcription of FASN	SIGNOR-242884
Q9H2X6	Q09472	1	phosphorylation	up-regulates activity	0.611	Furthermore, HIPK2 forms a complex with the coactivator p300 and AML1, phosphorylates p300 at multiple Serine/Threonine sites and activates p300 HAT activity and coactivator function.	SIGNOR-278943
P08651	Q9HCE7	0	ubiquitination	down-regulates quantity	0.329	In addition, Smurf1 knockdown also blocked the degradation of endogenous NFI-C in response to TGF-beta1 (XREF_FIG).\|In particular, Smurf1 and Smurf2 markedly increased the polyubiquitination of NFI-C in the presence of TGF-beta1 (XREF_FIG and XREF_SUPPLEMENTARY).	SIGNOR-278753
Q9P2F6	P63000	1	gtpase-activating protein	down-regulates activity	0.436	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-260473
P35869	Q16678	1	transcriptional regulation	up-regulates quantity by expression	0.489	The formation of the AHR/ARNT dimerization complex converts the AHR into a high affinity DNA-binding form that recognizes specific DNA recognition sites termed DREs. In this manner, the agonist activated AHR upregulates a battery of target genes, including those involved in the metabolism of chemical carcinogens, such as CYP1A1 and CYP1B1 .	SIGNOR-253642
Q13093	Q9Y4A8	0	transcriptional regulation	up-regulates quantity by expression	0.363	Moreover, we demonstrated that nuclear factor erythroid 2-related factor 3 (Nrf3) regulates Pla2g7 gene expression through direct binding to the promoter regions of Pla2g7 gene.	SIGNOR-268979
Q8N122	Q9UPZ9	0	phosphorylation	up-regulates	0.2	Our findings demonstrate an important role for ick in modulating the activity of mtorc1 through phosphorylation of raptor thr-908 and thus implicate a potential signaling mechanism by which ick regulates cell proliferation and division.	SIGNOR-196198
P49768	Q00535	0	phosphorylation	up-regulates	0.51	Cyclin-dependent kinase-5/p35 phosphorylates presenilin 1 to regulate carboxy-terminal fragment stabilityhere we demonstrate that cyclin dependent kinase-5/p35 (cdk5/p35) phosphorylates ps1 on threonine(354) within c-ps1 both in vitro and in vivo. Threonine(354) phosphorylation functions to selectively stabilize c-ps1.	SIGNOR-89145
O15111	Q13546	1	phosphorylation	down-regulates activity	0.54	Indeed, IKKa and IKKb may directly repress RIPK1 kinase activity by addition of an inhibitory phosphate group on RIPK1.\|Mass spectrometry analysis of kinase assays performed with recombinant proteins allowed us to identify Ser166, Ser331, and Ser416 as highly conserved RIPK1 residues phosphorylated by IKKa and IKKb.	SIGNOR-278927
Q13422	P43405	0	phosphorylation	up-regulates	0.404	Syk phoshorylatesikarosat unique c-terminal serine phosphorylation sites s358 and s361, thereby augmenting its nuclear localization and sequence-specific dna binding activity. Mechanistically, we establish that syk-inducedikarosactivation is essential for its nuclear localization and optimal transcription factor function.	SIGNOR-199100
Q5VST9	Q8WZ42	0	relocalization	up-regulates quantity	0.58	Ankyrin-B is targeted to the M-line via its interaction with the C-terminal domain of the large sarcomeric protein obscurin. Obscurin is targeted to the M-line via its N-terminal interactions with myomesin and titin. This population of ankyrin-B recruits B56α, a regulatory subunit of protein phosphatase 2A, to the M-line where the phosphatase may regulate the phosphorylation status of contractile and signalling proteins.	SIGNOR-266728
O15550	Q01543	1	transcriptional regulation	down-regulates quantity by repression	0.2	Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase	SIGNOR-260034
Q8IZQ1	Q92997	1	relocalization	down-regulates quantity by destabilization	0.251	Our data taken together with the known role of ALFY in autophagy, demonstrate specific targeting and autophagy-mediated removal of DVL3 by hALFY.	SIGNOR-266793
O60716	P49674	0	phosphorylation	down-regulates	0.288	Moreover, in response to wnt3a, p120-catenin is phosphorylated at ser268, a modification dependent on ck1epsilon activity, which disrupts its interaction with e-cadherin and, subsequently, with lrp5/6, promoting the release of ck1epsilon/p120-catenin from the wnt receptor complex.	SIGNOR-24443
P15927	P78527	0	phosphorylation	down-regulates activity	0.579	We showed previously that UV irradiation increases phosphorylation of the p34 subunit of human replication protein A (RPA) and that this hyperphosphorylation correlated with loss of activity of the DNA replication complex. \| we detected phosphorylation of the RPA complex by DNA-PK on RPA-p34 sites Ser-23, Ser-29, and Ser-11, -12, or -13	SIGNOR-248981
P23443	Q16873	1	phosphorylation	down-regulates activity	0.2	Here, we identified Ser(36) as the major p70S6k phosphorylation site, along with a low frequency site at Thr(40), using an in vitro phosphorylation assay combined with mass spectrometry. Cellular LTC4S activity is suppressed by PKC-mediated phosphorylation, and recently a downstream p70S6k was shown to play an important role in this process.	SIGNOR-277256
O95372	P17677	1	deacetylation	down-regulates quantity by destabilization	0.477	Acyl-protein thioesterase 2 catalyzes the deacylation of peripheral membrane-associated GAP-43. In this work, we investigated the deacylation of growth-associated protein-43 (GAP-43), a dually acylated protein at cysteine residues 3 and 4. Thus, the results demonstrate that APT-2 is the protein thioesterase involved in the acylation/deacylation cycle operating in GAP-43 subcellular distribution.we demonstrated that the reduction in the protein level was abrogated when cells were also treated with proteasome inhibitors (chloroquine, MG132 and lactacystin) which strongly suggest that GAP-43 deacylation is an early and necessary step for its later ubiquitination and degradation by the proteasome. In addition, it also suggests that acyl-protein thioesterase levels not only regulate palmitate turnover but also global protein turnover of GAP-43.	SIGNOR-266768
P54278	P04637	0	transcriptional regulation	up-regulates quantity	0.582	.... numerous potentially novel targets, including the DNA mismatch repair genes MLH1 and PMS2. Both of these genes were determined to be responsive to DNA damage and p53 activation in normal human fibroblasts, and have p53-response elements within their first intron.	SIGNOR-257604
Q9Y618	P24941	0	phosphorylation	down-regulates activity	0.429	Cdk2 and Pin1 negatively regulate the transcriptional corepressor SMRT.\|Cdk2 phosphorylates SMRT at consensus Cdk motifs to generate Pin1 binding sites and consequently targets SMRT for degradation, the latter also requiring the PPIase activity of Pin1 (XREF_FIG).	SIGNOR-278306
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
Q13107	P31749	0	phosphorylation	up-regulates quantity by stabilization	0.465	AKT-mediated phosphorylation relocates nuclear USP4 to the cytoplasm and membrane and is required for maintaining its protein stability.	SIGNOR-273482
Q92502	P61586	1	gtpase-activating protein	down-regulates activity	0.557	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-260519
P00519	Q9NRM7	0	phosphorylation	down-regulates activity	0.362	Inhibition of c-Abl by Lats2 was mediated through Lats2 interaction with and phosphorylation of c-Abl. Lats2 phosphorylates c-Abl at Thr197 in vitro.	SIGNOR-276497
Q14790	P12931	0	phosphorylation	down-regulates	0.453	Src kinase phosphorylates caspase-8 on tyr380: a novel mechanism of apoptosis suppressionwe identified caspase-8 as a new substrate for src kinase. Phosphorylation occurs on tyr380, situated in the linker region between the large and the small subunits of human procaspase-8, and results in downregulation of caspase-8 proapoptotic function	SIGNOR-146127
P04637	Q9UNH5	0	dephosphorylation	down-regulates activity	0.401	The human Cdc14 phosphatases interact with and dephosphorylate the tumor suppressor protein p53\|. Furthermore, the hCdc14 phosphatases were found to dephosphorylate p53 specifically at the p34Cdc2/clb phosphorylation site (p53-phosphor-Ser315)\|Earlier studies showed that Ser315 phosphorylation increases the sequence-specific DNA binding capacity of p53, suggesting that Ser315 phosphorylation is an activating modification	SIGNOR-248828
Q99683	O14733	1	phosphorylation	up-regulates	0.594	Ask1 is a member of a mapkkk family and functions as an upstream kinase engaged in c-jun nh2-terminal kinase (jnk)/p38 signaling via the phosphorylation and activation of mapkks, such as mkk3, -4, -6, and -7	SIGNOR-161766
Q9UKI8	Q96PY6	1	phosphorylation	up-regulates activity	0.29	TLK1 phosphorylated NEK1 at T141, which lies in the kinase domain, and caused an increase in its activity.	SIGNOR-275840
P78563	P31751	0	phosphorylation	down-regulates activity	0.2	AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively	SIGNOR-276196
O94856	Q12955	1	relocalization	up-regulates quantity	0.745	Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.	SIGNOR-266717

P10451

P08254

0

cleavage

up-regulates activity

0.67

In this study, we found a novel motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved mouse OPN binds to α9β1 integrin. Importantly, this novel motif is involved in the development of anti-type II collagen antibody-induced arthritis (CAIA). This study provides the first in vitro and in vivo evidence that OPN cleavage by MMP-3/7 is an important regulatory mechanism for CAIA.

SIGNOR-253320

Q8IVF5

P63000

1

guanine nucleotide exchange factor

up-regulates activity

0.589

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-260578

Q96GD4

Q99986

0

phosphorylation

up-regulates activity

0.429

In the VRK1 overexpression of experiment, VRK1 caused a significant stabilization of AURKB, with no change in level after 24h, which is consistent with protection of AURKB against its known degradation by ubiquitylation .|The phosphorylation of AURKB by VRK1 and VRK1 by AURKB was tested using a kinase-dead form as substrate.

SIGNOR-280160

Q8TDX7

Q15058

1

phosphorylation

up-regulates activity

0.371

Nek7 direct phosphorylation is required for the anaphase localization of Kif14. we generated an EGFP-Kif14-5A construct in which Ser56, Ser607, Ser1217, Ser1219, and Ser1220 were all mutated to Ala. When transfected into HeLa cells, EGFP-Kif14-5A was expressed to similar levels as WT Kif14 (Fig. S3 C), but its localization to the central spindle in anaphase cells was completely abolished (Fig. 6 C).

SIGNOR-266420

Q08209

Q969Q1

0

ubiquitination

down-regulates quantity

0.26

First, downregulation of MuRF1 significantly attenuates degradation of CnA in cardiomyocytes in vitro, indicating that endogenous MuRF1 negatively regulates the stability of CnA in a cell-autonomous manner.|Furthermore, MuRF1 directly ubiquitinated CnA in vitro.|These results suggest that MuRF1 directly polyubiquitinates CnA.

SIGNOR-278736

P19838

O15111

0

phosphorylation

down-regulates quantity by destabilization

0.747

All residues of p105 phosphorylated by ikka are c-terminal; the major phosphorylation region contains three serines (ser923; ser927;ser932) and two threonines (thr927 and thr391).

SIGNOR-70449

Q12947

Q9H1B7

1

transcriptional regulation

up-regulates quantity by expression

0.253

FOXF2 directly bound the promoter of E3 ligase interferon regulatory factor 2-binding protein-like (IRF2BPL) and induced its transcriptional expression. IRF2BPL in turn interacted with β-catenin, increasing its ubiquitination and degradation.

SIGNOR-267152

P42772

Q00532

0

phosphorylation

up-regulates activity

0.2

We demonstrated that depletion of CDKL1 notably upregulated the protein expression of P15. P15 is shown to be a target of CDKL1 in CRC, either direct or indirect.

SIGNOR-273862

P48729

Q9H6E5

1

phosphorylation

up-regulates activity

0.267

We identified a phosphorylated residue (serine 6, S6) on Star-PAP in the zinc finger region, the domain required for PIPKIα interaction. We show that S6 is phosphorylated by CKIα within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIα.

SIGNOR-273619

Q13009

Q15835

0

phosphorylation

down-regulates activity

0.2

For example, RhoK phosphorylates and inhibits TIAM1, STEF, and PAR3; disrupts the polarity complex; and prevents Rac activation ( xref ).

SIGNOR-279995

P11388

P05771

0

phosphorylation

up-regulates activity

0.359

Here, we have shown that the enzymatic activity of topoisomerase II alpha protein purified from HeLa cell nuclei was strongly enhanced following phosphorylation by protein kinase C. | Site-directed mutagenesis studies indicated that phosphorylation of serine 29 generated both of these phosphopeptides.

SIGNOR-249195

Q05655

Q14247

1

phosphorylation

up-regulates activity

0.246

Together these findings demonstrate that phosphorylation of cortactin on S405 and S418 residues is required for its interaction with WAVE2 in MCP1-induced cytoskeleton remodeling, facilitating HASMC migration. In addition, the MCP1-induced cortactin phosp

SIGNOR-260890

P17612

P23677

1

phosphorylation

up-regulates activity

0.327

Two isoforms of the inositol 1,4,5-trisphosphate 3-kinase have been identified, the A form and the B form. phosphorylation of isoform A by the cyclic AMP-dependent protein kinase increased activity 1.5-fold, whereas phosphorylation of isoform B decreased activity by 45%. major phosphorylation sites in the protein are Ser119 for PKA. Ser119 in the A isoform is conserved in the B isoform as Ser328

SIGNOR-249994

P30307

Q8TDC3

0

phosphorylation

down-regulates

0.483

Overexpression of hssad1 resulted in an increased phosphorylation of cdc25c on ser-216 in vivo.Phosphorylation of cdc25 triggers cell-cycle arrest by the sequestration of cdc25 by 14-3-3

SIGNOR-56473

P24588

P48454

1

relocalization

up-regulates activity

0.262

Using a viral-mediated molecular replacement strategy in rat hippocampal slices, we found that AKAP is required for NMDA receptor-dependent long-term depression solely because of its interaction with calcineurin

SIGNOR-261291

Q92630

Q00987

0

ubiquitination

down-regulates quantity by destabilization

0.57

Under normal conditions, nuclear and not cytoplasmic DYRK2 is ubiquitinated by MDM2, resulting in its constitutive degradation.|Upon exposure to genotoxic stress, ATM phosphorylates DYRK2 at Thr-33 and Ser-369, which enables DYRK2 to escape from degradation by dissociation from MDM2 and to induce the kinase activity toward p53 at Ser-46 in the nucleus.

SIGNOR-275579

P15056

P00519

1

phosphorylation

up-regulates activity

0.275

BRAF V600E activates Abl and Arg.|Rather, BRAF V600E, a serine threonine kinase, induced Abl threonine phosphorylation (XREF_FIG), and tyrosine phosphorylation of kinase-inactive Abl or Arg, which lack the ability to autophosphorylate (XREF_FIG).

SIGNOR-278914

P17252

P49840

1

phosphorylation

down-regulates

0.345

Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.

SIGNOR-115714

Q8TAU0

Q13477

1

transcriptional regulation

up-regulates quantity by expression

0.428

We provide evidence that NKX2.3 can activate MAdCAM-1 transcription directly

SIGNOR-266219

P17252

Q96AX2

1

phosphorylation

down-regulates activity

0.2

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

SIGNOR-273803

Q13233

Q13158

1

phosphorylation

down-regulates activity

0.503

The results clearly show that fadd phosphorylation at ser194 affects functions both upstream and downstream of the mekk1/mkk7/jnk1 pathway and is closely associated with chemosensitivity in prostate cancer cells

SIGNOR-123168

Q9H4B4

Q99986

1

phosphorylation

up-regulates

0.474

Vrk1 does not phosphorylate plk3, but plk3 phosphorylates the c-terminal region of vrk1 in ser342. Vrk1 with substitutions in s342 is catalytically active but blocks golgi fragmentation, indicating that its specific phosphorylation is necessary for this process.

SIGNOR-182858

P49810

P48730

0

phosphorylation

up-regulates activity

0.364

In vitro the large hydrophilic loop of PS-2 between transmembrane domains 6 and 7 can be phosphorylated by casein kinase-1 (CK-1) and CK-2, but not by PKA or PKC. Quantitative analysis of in vitro phosphorylation demonstrates the presence of two phosphorylation sites for CK-1 and a single site for CK-2. A deletion analysis revealed that the CTF of PS-2 is phosphorylated in vivo within an acidic sequence containing three potential phosphorylation sites for CKs (serines 327, 330, and 335). These data suggest that CK type protein kinases phosphorylate the CTF of PS-2 within its hydrophilic loop domain in vivo. Interestingly, the potential phosphorylation sites are located directly adjacent to the recently identified caspase cleavage sites.

SIGNOR-250802

P06241

Q96J84

1

phosphorylation

up-regulates activity

0.2

Here we have characterized Neph1, another SD component, as a novel substrate of SFK. Fyn interacts with and phosphorylates the cytoplasmic domain of Neph1 in vitro and in intact cells. Both tyrosine 637 and 638 of Neph1 are crucial for Neph1-Grb2 binding.

SIGNOR-262746

P29590

P28482

0

phosphorylation

up-regulates

0.359

We report here that as(2)o(3) treatment induces phosphorylation of the pml protein through a mitogen-activated protein (map) kinase pathway. Increased pml phosphorylation is associated with increased sumoylation of pml and increased pml-mediated apoptosis.

SIGNOR-124248

P25116

P07384

0

cleavage

up-regulates activity

0.376

PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus

SIGNOR-263559

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

Q9NS28

Q13976

0

phosphorylation

up-regulates activity

0.332

Cyclic AMP- and cyclic GMP-dependent kinases (PKA, PKG) inhibit the interaction of RGS18 and 14-3-3 by phosphorylating S216. S216 phosphorylation might activate PP1 leading to dephosphorylation of both 14-3-3 binding sites, S49 and S218, and detachment of 14-3-3. Removal of 14-3-3 activates RGS18 to turn off Gq signaling thus contributing to platelet inhibition.

SIGNOR-273785

P17676

Q15418

0

phosphorylation

up-regulates activity

0.683

13 The data presented support previous findings that C/EBPbeta can be a molecular target of RSK1, 16 but provide the first indication that RSK1 can phosphorylate and activate C/EBPbeta to mediate the IL-6 signalling events in cholangiocarcinoma.|As mentioned above, RSK1 has been shown to activate C/EBPbeta in hepatic stellate cells in an experimental model of liver fibrosis.

SIGNOR-280112

P78563

Q05513

0

phosphorylation

up-regulates activity

0.2

Here, we identified ADAR2 as a direct substrate of PKCζ in CRC cells. Phosphorylation of ADAR2 regulates its editing activity, which is required to maintain miR-200 steady-state levels, suggesting that the PKCζ/ADAR2 axis regulates miR-200 secretion through RNA editing.

SIGNOR-277391

Q00987

P08069

1

ubiquitination

down-regulates quantity by destabilization

0.66

We could prove that Mdm2 physically associates with IGF-1R and that Mdm2 causes IGF-1R ubiquitination in an in vitro assay.

SIGNOR-278571

Q969W9

P49910

0

transcriptional regulation

down-regulates quantity by repression

0.271

ZNF165 drives the unrestrained activation of transforming growth factor β (TGFβ) signalling by directly inactivating the expression of negative feedback pathway regulators, SMURF2, SMAD7 and PMEPA1.

SIGNOR-266094

O14965

O15350

1

phosphorylation

down-regulates activity

0.449

Aurora-A inhibits p73 and p53 transactivation functions through a common molecular mechanism.|We report that Aurora-A phosphorylation of p73 at serine235 abrogates its transactivation function and causes cytoplasmic sequestration in a complex with the chaperon protein mortalin.

SIGNOR-278263

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

O15379

Q9UHD2

0

phosphorylation

up-regulates activity

0.2

The feedback of activation of HDAC3 by TBK1 was able to further enhance IFN production and IFN-STAT activation.|We found that HDAC3 could be phosphorylated by TBK1.

SIGNOR-279662

P45983

Q99640

1

phosphorylation

up-regulates

0.336

A kinase assay using gst-myt1 revealed that active jnk1 or jnk3, but not jnk2, phosphorylated myt1 in vitro.

SIGNOR-183899

O15264

Q6JBY9

1

phosphorylation

down-regulates activity

0.419

CapZIP was also phosphorylated rapidly by SAPK3/p38γ and SAPK4/p38δ, and even faster and more extensively by JNK1α1, these protein kinases phosphorylating CapZIP in vitro to >3, approx. 2 and >5 mol of phosphate/mol of protein respectively within a few minutes. Following tryptic digestion and C18 chromatography, further sites phosphorylated by JNK1α1 were identified as Ser-68, Ser-83 and Ser-216 (results not shown), and are highlighted in Figure 3.Using this antibody, we showed by immunoblotting that bacterially expressed CapZIP was phosphorylated at Ser-108 by SAPK4/p38δ, JNK1α1 and ERK2 in vitro, as well as by SAPK3/p38γ (results not shown).An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.

SIGNOR-263084

Q9UHD2

Q13137

1

phosphorylation

up-regulates activity

0.795

Furthermore, we found that TBC1D9-regulated TBK1 activation and recruitment of NDP52 and ULK1 complex to damaged mitochondria (Fig.\u00a0 xref ).|TBK1 can phosphorylate p62, OPTN, and NDP52 to promote selective autophagy by facilitating their interaction with LC3, ubiquitin, and RAB35, respectively xref , xref , xref .

SIGNOR-280151

O14522

P06241

0

phosphorylation

down-regulates activity

0.414

Synapse formation by PTPRT was inhibited by phosphorylation of tyrosine 912 within the membrane-proximal catalytic domain of PTPRT by Fyn. This tyrosine phosphorylation reduced phosphatase activity of PTPRT

SIGNOR-275543

Q9UD71

Q00535

0

phosphorylation

up-regulates activity

0.777

We find that DARPP-32 is converted into an inhibitor of PKA when phosphorylated at threonine 75 by cyclin-dependent kinase 5 (Cdk5). Cdk5 phosphorylates DARPP-32 in vitro and in intact brain cells. Phospho-Thr 75 DARPP-32 inhibits PKA in vitro by a competitive mechanism.

SIGNOR-250671

Q9P0L0

Q14721

0

relocalization

up-regulates quantity

0.2

Confirmation that Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA knockdown, and Förster resonance energy transfer (FRET)-based assays.|As Kv2.1 accumulates on the surface it begins to bind ER VAPs and form the large and stable membrane junctions.

SIGNOR-262122

P13569

Q13976

0

phosphorylation

up-regulates

0.506

Direct amino acid sequencing and peptide mapping of cf-2 revealed that serines 660, 700, 737, and 813 as well as serine 768, serine 795, or both were phosphorylated by pka and pkgcftr possesses a large cluster of strict dibasic consensus sites for phosphorylation by protein kinase a (pka) in the r-domain and an obligatory dependence on phosphorylation is a hallmark of cftr cl(-) channel function

SIGNOR-18249

O00444

Q8NHV4

1

phosphorylation

up-regulates activity

0.593

We found that PLK4-mediated phosphorylation of NEDD1 at its S325 amino acid residue directly promotes both NEDD1 binding to SAS-6 and recruiting SAS-6 to the centrosome. |Collectively, our results demonstrate that PLK4-regulated NEDD1 facilitates initiation of the cartwheel assembly and of daughter centriole biogenesis in mammals.

SIGNOR-272996

P40763

Q13627

0

phosphorylation

up-regulates activity

0.265

DYRK1A overexpression promotes STAT3 activity by phosphorylating STAT3 at Ser727 and contributes to reduced neuronal production and increased astroglial generation in DS.

SIGNOR-279992

Q9UM47

P00533

0

phosphorylation

up-regulates activity

0.593

Here, we report that treatment of EGFR mutated lung cancer cell lines with erlotinib, while showing robust cell death, enriches the ALDH+ stem like cells through EGFR dependent activation of Notch3.|We also find a kinase-dependent physical association between the Notch3 and EGFR receptors and tyrosine phosphorylation of Notch3.

SIGNOR-280002

P43629

P68400

0

phosphorylation

up-regulates quantity by stabilization

0.2

Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of Ser(394) by protein kinase C slightly suppresses KIR3DL1 inhibitory function, and reduces receptor internalization and turnover.Both CKII and PKC phosphorylate KIR3DL1 in vitro. Ser364 can be phosphorylated after phosphorylation of Ser367 by CKII. It seems that phosphorylation of 3DL1 by CK does not significantly affect receptor inhibitory function or turnover, at least in the assays that we have used so far.

SIGNOR-276077

Q96J02

P08151

1

ubiquitination

down-regulates

0.578

The consequent activation of_ itch, together with the recruitment of gli1 through direct binding with_ numb, allows gli1 to enter into the complex, resulting in gli1 ubiquitination and degradation. we demonstrate that the hedgehog transcription factor gli1 is targeted by numb for itch-dependent ubiquitination, which suppresses hedgehog signals, thus arresting growth and promoting cell differentiation

SIGNOR-150847

P62714

Q9UIC8

0

methylation

up-regulates activity

0.661

Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits |The PP2A core enzyme was methylated by a PP2A-specific leucine carboxyl methyltransferase (LCMT1)

SIGNOR-265751

Q9Y5U4

P28324

0

transcriptional regulation

up-regulates quantity by expression

0.2

Under these conditions, a significant reduction in INSIG2 expression was only observed when SAP1a siRNA was used. These observations provide supporting evidence that SAP1a may be one of the transactivators of the human INSIG2 promoter.

SIGNOR-261592

P22681

P09619

1

polyubiquitination

down-regulates quantity by destabilization

0.629

Overexpression of wild type Cbl in NIH3T3 cells led to an enhancement of the ligand-dependent ubiquitination and subsequent degradation of the PDGFRbeta, as observed with PDGFRalpha.

SIGNOR-272549

O15111

Q9Y618

1

phosphorylation

down-regulates

0.416

Nf-kappab transcription requires ikkalpha to phosphorylate smrt on chromatin, stimulating the exchange of corepressor for coactivator complexes. Ikk directly phosphorylates smrt to stimulate nuclear export. Ikkalpha orchestrates smrt derepression, a prerequisite for nf-kappab transcription and survival.

SIGNOR-129956

Q13153

P23975

1

phosphorylation

down-regulates activity

0.2

PAK1 negatively regulates the activity of the Rho exchange factor NET1.|Specifically, PAK1 phosphorylates NET1 on three sites in vitro : serines 152, 153, and 538.

SIGNOR-280054

P01588

Q16665

0

transcriptional regulation

up-regulates quantity by expression

0.643

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix transcription factor that regulates hypoxia-inducible genes including the human erythropoietin (EPO) gene.

SIGNOR-253695

P12931

O14746

1

phosphorylation

down-regulates

0.418

Hydrogen peroxide triggers nuclear export of telomerase reverse transcriptase via src kinase family-dependent phosphorylation of tyrosine 707

SIGNOR-102097

P28482

P29590

1

phosphorylation

up-regulates

0.359

We report here that as(2)o(3) treatment induces phosphorylation of the pml protein through a mitogen-activated protein (map) kinase pathway. Increased pml phosphorylation is associated with increased sumoylation of pml and increased pml-mediated apoptosis.

SIGNOR-124248

Q13315

O15360

1

phosphorylation

up-regulates

0.407

The s1449a mutant failed to completely correct a variety of fa-associated phenotypes. The dna damage response is coordinated by phosphorylation events initiated by apical kinases atm (ataxia telangectasia mutated) and atr (atm and rad3-related), and atr is essential for proper fa pathway function. Serine 1449 is in a consensus atm/atr site

SIGNOR-182949

P49407

Q14940

1

relocalization

down-regulates activity

0.401

Internalization of the Na(+)/H(+) exchanger NHE5 into recycling endosomes is enhanced by the endocytic adaptor proteins beta-arrestin1 and -2, best known for their preferential recognition of ligand-activated G protein-coupled receptors (GPCRs)

SIGNOR-275505

Q9Y243

P78563

1

phosphorylation

down-regulates activity

0.2

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

SIGNOR-276195

Q8WUI4

P67775

0

dephosphorylation

up-regulates activity

0.317

Phosphorylation of conserved serine residues triggers association with 14-3-3 proteins and cytoplasmic relocalization of class IIa HDACs, which leads to the derepression of their target genes. |Here we identify PP2A as a phosphatase responsible for dephosphorylating the 14-3-3 binding sites in class IIa HDACs.|we demonstrate that PP2A constitutively dephosphorylates the class IIa member HDAC7 to control its biological functions as a regulator of T cell apoptosis and endothelial cell functions.

SIGNOR-248649

Q6EIG7

Q13191

0

ubiquitination

down-regulates quantity by destabilization

0.2

Furthermore, we found that Cbl-b, an E3 ubiquitin ligase, mediates the ubiquitination and degradation of the activated Dectin-2 and Dectin-3 to negatively regulate CLR mediated innate immune responses against fungal infections.

SIGNOR-278625

Q8IW41

O43524

1

phosphorylation

up-regulates activity

0.475

Analysis of mutant alleles of FoxO3a showed that MK5 phosphorylated FoxO3a predominantly at S215, but that mutation of four of the identified sites was required to essentially abolish phosphorylation of FoxO3a by MK5 (\u201c4A\u201d) ( Figure\u00a04 C and data not shown).|MK5 phosphorylates and activates the transcription factor FoxO3a and potentially other FoxO factors.

SIGNOR-279469

P11413

P12931

0

phosphorylation

up-regulates activity

0.274

Here, we show that tyrosine kinase c-Src interacts with and phosphorylates G6PD at Tyr 112. This phosphorylation enhances catalytic activity of G6PD by dramatically decreasing its Km value and increasing its Kcat value for substrate glucose-6-phosphate.

SIGNOR-277550

Q13233

P46531

1

phosphorylation

down-regulates activity

0.367

As a result, MEKK1 suppresses the Notch1 intracellular domain protein stability and transcriptional activity.|We confirmed that MEKK1 binds to Notch1 intracellular domain and phosphorylates the Notch1 intracellular domain Threonine 2512 residue.

SIGNOR-279628

Q96BN8

P0CG47

1

cleavage

up-regulates quantity

0.671

Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.

SIGNOR-270819

Q92585

P62805

1

acetylation

down-regulates activity

0.2

We speculated that maml1, in addition to recruiting p300, might directly interact with histones to facilitate histone acetylation. We had observed acetylation of the histones h3 and h4.

SIGNOR-153041

P20265

O75030

1

transcriptional regulation

up-regulates quantity by expression

0.437

We further demonstrate that BRN2 induces MITF transcription through a binding site located at 50/36 of the MITF promoter

SIGNOR-249616

P08590

P42574

0

cleavage

down-regulates quantity by destabilization

0.377

By sequencing and site-directed mutagenesis, a noncanonical cleavage site for caspase-3 was mapped to the C-terminal DFVE(135)G motif. We demonstrated that vMLC1 cleavage in failing myocardium in vivo is associated with a morphological disruption of the organized vMLC1 staining of sarcomeres, and with a reduction in myocyte contractile performance.

SIGNOR-270593

Q13363

P38398

1

transcriptional regulation

down-regulates quantity by repression

0.603

Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor with oncogenic potential. We found CtBP1 was recruited to the promoter regions of Brca1 and E-cadherin genes in breast cancer cells.

SIGNOR-259196

P00533

P0DP23

1

phosphorylation

down-regulates

0.404

Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.

SIGNOR-24778

P17813

P12931

0

phosphorylation

down-regulates quantity by destabilization

0.385

We identified epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) as Src-activators that induce endoglin turnover following (612)YIY(614) phosphorylation.

SIGNOR-276654

P18146

Q9Y251

1

transcriptional regulation

up-regulates quantity by expression

0.37

Promoter CpG hypomethylation and transcription factor EGR1 hyperactivate heparanase expression in bladder cancer.

SIGNOR-254267

P36956

P49327

1

transcriptional regulation

up-regulates quantity by expression

0.495

Ultimately, both the AKT and MAPK transduction pathways regulate FASN expression through the modulation of expression of sterol regulatory element-binding protein (SREBP)-1c, which binds to regulatory elements in the FASN promoter. Proto-oncogene FBI-1 (Pokemon), a transcription factor of the bric--brac tramtrack broad complex/pox viruses and zinc fingers (BTB/POZ) domain family, interacts directly with SREBP-1c through its DNA-binding domain to synergistically activate the transcription of FASN

SIGNOR-242884

Q9H2X6

Q09472

1

phosphorylation

up-regulates activity

0.611

Furthermore, HIPK2 forms a complex with the coactivator p300 and AML1, phosphorylates p300 at multiple Serine/Threonine sites and activates p300 HAT activity and coactivator function.

SIGNOR-278943

P08651

Q9HCE7

0

ubiquitination

down-regulates quantity

0.329

In addition, Smurf1 knockdown also blocked the degradation of endogenous NFI-C in response to TGF-beta1 (XREF_FIG).|In particular, Smurf1 and Smurf2 markedly increased the polyubiquitination of NFI-C in the presence of TGF-beta1 (XREF_FIG and XREF_SUPPLEMENTARY).

SIGNOR-278753

Q9P2F6

P63000

1

gtpase-activating protein

down-regulates activity

0.436

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-260473

P35869

Q16678

1

transcriptional regulation

up-regulates quantity by expression

0.489

The formation of the AHR/ARNT dimerization complex converts the AHR into a high affinity DNA-binding form that recognizes specific DNA recognition sites termed DREs. In this manner, the agonist activated AHR upregulates a battery of target genes, including those involved in the metabolism of chemical carcinogens, such as CYP1A1 and CYP1B1 .

SIGNOR-253642

Q13093

Q9Y4A8

0

transcriptional regulation

up-regulates quantity by expression

0.363

Moreover, we demonstrated that nuclear factor erythroid 2-related factor 3 (Nrf3) regulates Pla2g7 gene expression through direct binding to the promoter regions of Pla2g7 gene.

SIGNOR-268979

Q8N122

Q9UPZ9

0

phosphorylation

up-regulates

0.2

Our findings demonstrate an important role for ick in modulating the activity of mtorc1 through phosphorylation of raptor thr-908 and thus implicate a potential signaling mechanism by which ick regulates cell proliferation and division.

SIGNOR-196198

P49768

Q00535

0

phosphorylation

up-regulates

0.51

Cyclin-dependent kinase-5/p35 phosphorylates presenilin 1 to regulate carboxy-terminal fragment stabilityhere we demonstrate that cyclin dependent kinase-5/p35 (cdk5/p35) phosphorylates ps1 on threonine(354) within c-ps1 both in vitro and in vivo. Threonine(354) phosphorylation functions to selectively stabilize c-ps1.

SIGNOR-89145

O15111

Q13546

1

phosphorylation

down-regulates activity

0.54

Indeed, IKKa and IKKb may directly repress RIPK1 kinase activity by addition of an inhibitory phosphate group on RIPK1.|Mass spectrometry analysis of kinase assays performed with recombinant proteins allowed us to identify Ser166, Ser331, and Ser416 as highly conserved RIPK1 residues phosphorylated by IKKa and IKKb.

SIGNOR-278927

Q13422

P43405

0

phosphorylation

up-regulates

0.404

Syk phoshorylatesikarosat unique c-terminal serine phosphorylation sites s358 and s361, thereby augmenting its nuclear localization and sequence-specific dna binding activity. Mechanistically, we establish that syk-inducedikarosactivation is essential for its nuclear localization and optimal transcription factor function.

SIGNOR-199100

Q5VST9

Q8WZ42

0

relocalization

up-regulates quantity

0.58

Ankyrin-B is targeted to the M-line via its interaction with the C-terminal domain of the large sarcomeric protein obscurin. Obscurin is targeted to the M-line via its N-terminal interactions with myomesin and titin. This population of ankyrin-B recruits B56α, a regulatory subunit of protein phosphatase 2A, to the M-line where the phosphatase may regulate the phosphorylation status of contractile and signalling proteins.

SIGNOR-266728

O15550

Q01543

1

transcriptional regulation

down-regulates quantity by repression

0.2

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

SIGNOR-260034

Q8IZQ1

Q92997

1

relocalization

down-regulates quantity by destabilization

0.251

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

SIGNOR-266793

O60716

P49674

0

phosphorylation

down-regulates

0.288

Moreover, in response to wnt3a, p120-catenin is phosphorylated at ser268, a modification dependent on ck1epsilon activity, which disrupts its interaction with e-cadherin and, subsequently, with lrp5/6, promoting the release of ck1epsilon/p120-catenin from the wnt receptor complex.

SIGNOR-24443

P15927

P78527

0

phosphorylation

down-regulates activity

0.579

We showed previously that UV irradiation increases phosphorylation of the p34 subunit of human replication protein A (RPA) and that this hyperphosphorylation correlated with loss of activity of the DNA replication complex. | we detected phosphorylation of the RPA complex by DNA-PK on RPA-p34 sites Ser-23, Ser-29, and Ser-11, -12, or -13

SIGNOR-248981

P23443

Q16873

1

phosphorylation

down-regulates activity

0.2

Here, we identified Ser(36) as the major p70S6k phosphorylation site, along with a low frequency site at Thr(40), using an in vitro phosphorylation assay combined with mass spectrometry. Cellular LTC4S activity is suppressed by PKC-mediated phosphorylation, and recently a downstream p70S6k was shown to play an important role in this process.

SIGNOR-277256

O95372

P17677

1

deacetylation

down-regulates quantity by destabilization

0.477

Acyl-protein thioesterase 2 catalyzes the deacylation of peripheral membrane-associated GAP-43. In this work, we investigated the deacylation of growth-associated protein-43 (GAP-43), a dually acylated protein at cysteine residues 3 and 4. Thus, the results demonstrate that APT-2 is the protein thioesterase involved in the acylation/deacylation cycle operating in GAP-43 subcellular distribution.we demonstrated that the reduction in the protein level was abrogated when cells were also treated with proteasome inhibitors (chloroquine, MG132 and lactacystin) which strongly suggest that GAP-43 deacylation is an early and necessary step for its later ubiquitination and degradation by the proteasome. In addition, it also suggests that acyl-protein thioesterase levels not only regulate palmitate turnover but also global protein turnover of GAP-43.

SIGNOR-266768

P54278

P04637

0

transcriptional regulation

up-regulates quantity

0.582

.... numerous potentially novel targets, including the DNA mismatch repair genes MLH1 and PMS2. Both of these genes were determined to be responsive to DNA damage and p53 activation in normal human fibroblasts, and have p53-response elements within their first intron.

SIGNOR-257604

Q9Y618

P24941

0

phosphorylation

down-regulates activity

0.429

Cdk2 and Pin1 negatively regulate the transcriptional corepressor SMRT.|Cdk2 phosphorylates SMRT at consensus Cdk motifs to generate Pin1 binding sites and consequently targets SMRT for degradation, the latter also requiring the PPIase activity of Pin1 (XREF_FIG).

SIGNOR-278306

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

Q13107

P31749

0

phosphorylation

up-regulates quantity by stabilization

0.465

AKT-mediated phosphorylation relocates nuclear USP4 to the cytoplasm and membrane and is required for maintaining its protein stability.

SIGNOR-273482

Q92502

P61586

1

gtpase-activating protein

down-regulates activity

0.557

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-260519

P00519

Q9NRM7

0

phosphorylation

down-regulates activity

0.362

Inhibition of c-Abl by Lats2 was mediated through Lats2 interaction with and phosphorylation of c-Abl. Lats2 phosphorylates c-Abl at Thr197 in vitro.

SIGNOR-276497

Q14790

P12931

0

phosphorylation

down-regulates

0.453

Src kinase phosphorylates caspase-8 on tyr380: a novel mechanism of apoptosis suppressionwe identified caspase-8 as a new substrate for src kinase. Phosphorylation occurs on tyr380, situated in the linker region between the large and the small subunits of human procaspase-8, and results in downregulation of caspase-8 proapoptotic function

SIGNOR-146127

P04637

Q9UNH5

0

dephosphorylation

down-regulates activity

0.401

The human Cdc14 phosphatases interact with and dephosphorylate the tumor suppressor protein p53|. Furthermore, the hCdc14 phosphatases were found to dephosphorylate p53 specifically at the p34Cdc2/clb phosphorylation site (p53-phosphor-Ser315)|Earlier studies showed that Ser315 phosphorylation increases the sequence-specific DNA binding capacity of p53, suggesting that Ser315 phosphorylation is an activating modification

SIGNOR-248828

Q99683

O14733

1

phosphorylation

up-regulates

0.594

Ask1 is a member of a mapkkk family and functions as an upstream kinase engaged in c-jun nh2-terminal kinase (jnk)/p38 signaling via the phosphorylation and activation of mapkks, such as mkk3, -4, -6, and -7

SIGNOR-161766

Q9UKI8

Q96PY6

1

phosphorylation

up-regulates activity

0.29

TLK1 phosphorylated NEK1 at T141, which lies in the kinase domain, and caused an increase in its activity.

SIGNOR-275840

P78563

P31751

0

phosphorylation

down-regulates activity

0.2

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

SIGNOR-276196

O94856

Q12955

1

relocalization

up-regulates quantity

0.745

Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.

SIGNOR-266717