GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P04637	Q8IW41	0	phosphorylation	up-regulates	0.76	Furthermore, we show that prak activates p53 by direct phosphorylation. prak phosphorylates p53 at ser37	SIGNOR-152847
P17676	P35638	0	transcriptional regulation	down-regulates quantity	0.668	We find that expression of CHOP, a nuclear protein that dimerizes avidly with C/EBP isoforms alpha and beta and directs the resulting heterodimer away from classic C/EBP-binding sites, markedly inhibits this differentiation process.	SIGNOR-255914
P52597	Q96JP5	0	ubiquitination	down-regulates quantity	0.2	Collectively, our results indicate that ZFP91 polyubiquitinated hnRNP F at Lys 185.\|We found that silencing ZFP91 increased hnRNP F protein levels, but not hnRNP F mRNA levels, while ectopically expressing ZFP91 decreased hnRNP F protein levels, but not hnRNP F mRNA levels.	SIGNOR-278802
Q00534	P19532	1	phosphorylation	up-regulates activity	0.2	CDK4 and CDK6 interact with TFEB and TFE3 in the nucleus We next investigated how CDK4 and CDK6 activate TFEB and TFE3 .\|CDK4 and CDK6 phosphorylate TFEB and TFE3.	SIGNOR-279517
Q5SQI0	Q71U36	1	acetylation	up-regulates quantity by stabilization	0.268	Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.\|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules	SIGNOR-272251
Q15120	P08559	1	phosphorylation	down-regulates activity	0.871	Activity of the mammalian pyruvate dehydrogenase complex is regulated by phosphorylation-dephosphorylation of the alpha subunit of the pyruvate dehydrogenase (e1) component. Phosphorylation is carried out by four pyruvate dehydrogenase kinase (pdk) isoenzymes.	SIGNOR-109647
Q86WV6	O43318	0	phosphorylation	up-regulates activity	0.2	Activated TAK1 directly mediates STING phosphorylation on serine 355, which facilitates its interaction with STING ER exit protein (STEEP) and thereby promotes its oligomerization and translocation to the ERGIC for subsequent activation	SIGNOR-277887
Q96SB4	Q07955	1	phosphorylation	up-regulates	0.799	These results suggest that the formation of complexes between sf2/asf and srpks, which is influenced by the phosphorylation state of sf2/asf, may have regulatory roles in the assembly and localization of this splicing factor.	SIGNOR-66465
P61586	B2RTY4	0	gtpase-activating protein	down-regulates activity	0.565	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-260508
Q13555	Q15746	1	phosphorylation	down-regulates activity	0.331	Phosphorylation of MLC kinase by CaM protein kinase II increased the dissociation constant of MLC kinase for calmodulin about 10 times without changing the Vmax. The location of the phosphorylation sites was identified by isolating and sequencing the tryptic phosphopeptides of MLC kinase. The preferred site was identified as serine 512 and the second site as serine 525. These sites are the same as the sites phosphorylated by cAMP-dependent protein kinase.	SIGNOR-250700
P35611	P17612	0	phosphorylation	down-regulates activity	0.311	Protein kinase A phosphorylates -adducin at three sites in the neck domain (Ser-408, ’436, and ’481) in addition to the MARCKS-related domain of both subunits. Phosphorylation by PKA, in contrast to PKC, reduced affinity of erythrocyte adducin for spectrin-F-actin complexes as well as activity of adducin in promoting binding of spectrin to F-actin.	SIGNOR-250331
P00746	P00751	1	cleavage	up-regulates activity	0.804	The resulting proconvertase C3bB is subsequently cleaved by factor D (FD), generating the AP C3 convertase C3bBb	SIGNOR-263488
Q96CF2	Q6PHR2	0	phosphorylation	down-regulates activity	0.286	CHMP4C was phosphorylated by recombinant ULK3 in these experiments, whereas CHMP4A and CHMP4B were not (Figure 7\u2014figure supplement 1A).	SIGNOR-279771
P29966	Q16512	0	phosphorylation	down-regulates activity	0.365	PRK1 phosphorylates MARCKS at the PKC sites: serine 152, serine 156 and serine 163.	SIGNOR-249671
P08559	Q13131	0	phosphorylation	up-regulates activity	0.2	AMPKα phosphorylates PDHA subunit on Ser295 and Ser314 to activate PDH complex	SIGNOR-276837
P53567	Q9NPD5	1	transcriptional regulation	up-regulates quantity by expression	0.2	Taken together, these findings suggest that the LPS-induced down-regulation of Oatp4 is likely due to reduction in the binding of HNF1alpha, C/EBP, HNF3, and RXR:RAR to the Oatp4 promoter.	SIGNOR-268986
Q96CG3	O14965	0	phosphorylation	up-regulates activity	0.2	Here, we report that Aurora A is essential for Thr9 phosphorylation of the TRAF-interacting protein TIFA, triggering activation of the NF-κB survival pathway in AML.	SIGNOR-273551
Q9ULU4	P00533	1	transcriptional regulation	down-regulates quantity by repression	0.2	Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported	SIGNOR-262040
Q9H0A0	P09874	1	acetylation	up-regulates quantity by stabilization	0.2	MORC2 directly interacts with PARP1. MORC2 mediates the interaction between PARP1 and NAT10 and thereby promotes NAT10-mediated PARP1 acetylation at K949, which blocks CHFR-mediated ubiquitination and degradation of PARP1.	SIGNOR-273715
P29350	Q13237	0	phosphorylation	up-regulates activity	0.2	PKGII directly phosphorylated and stimulated SHP-1 activity	SIGNOR-276288
P25054	O60566	0	phosphorylation	up-regulates activity	0.428	These findings support a model in which BubR1 kinase may directly regulate APC function involved in stable kinetochore microtubule attachment.\|Using purified components, BubR1 directly phosphorylates APC and forms a ternary complex with APC and microtubules.	SIGNOR-279393
Q14721	P12931	0	phosphorylation	up-regulates	0.479	In the present study we show that an n-terminal tyrosine of kv2.1 (y124), which is a known target of src kinase, is critical for the apoptotic current surge..Kv2.1-mediated k+ currents are also enhanced during non-injurious conditions through direct phosphorylation of intracellular n-terminal residue tyrosine 124 (y124) by src kinase	SIGNOR-187201
Q13131	O95863	1	phosphorylation	up-regulates quantity by stabilization	0.2	Serines 11 and 92 participate in the control of snail1 stability and positively regulate snail1 repressive function and its interaction with msin3a corepressor. Furthermore, serines 11 and 92 are required for snail1-mediated emt and cell viability, respectively. Pka and ck2 have been characterized as the main kinases responsible for in vitro snail1 phosphorylation at serine 11 and 92, respectively.	SIGNOR-161779
Q96GD4	Q8NG31	1	phosphorylation	down-regulates	0.2	To determine whether the combinatorial regulation of the kmn network by aurora b observed in vitro is critical to controlling kinetochore-microtubule attachments in vivo, we next investigated the effect of the phosphomimetic (to aspartate) and nonphosphorylatable (to alanine) mutants of dsn1, knl1, and ndc80 in vertebrate cells. We predicted that both types of mutations in critical phosphorylation sites would affect chromosome segregation, since preventing the inactivation of inappropriately attached kinetochores by aurora b (in the nonphosphorylatable mutant) or constitutively inactivating this attachment (in the phosphomimetic mutant).	SIGNOR-165502
P42574	P49768	1	cleavage	up-regulates activity	0.454	Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.	SIGNOR-261756
P17612	Q13085	1	phosphorylation	down-regulates activity	0.2	TC1 = Ser-2Ser(P)-Met-3Ser(P)-Gly-Leu; TC2 = Arg-Met-1Ser(P)-Phe- Cyclic-AMP-dependent protein kinase phosphorylates sites 1 and 2 exclusively, whereas the AMP-activated protein kinase phosphorylates sites 1 and 3, plus at least one other minor site.[…]The results suggest that phosphorylation of site 3 is primarily responsible for the large decrease in Vmax produced by the AMP-activated protein kinase, while phosphorylation of site 1 may be primarily responsible for the increase in A0.5 for citrate and more modest depression of Vmax produced by cyclic-AMP-dependent protein kinase and ACK2	SIGNOR-267714
P45983	Q6SZW1	1	phosphorylation	down-regulates activity	0.423	C-Jun N-terminal kinase (JNK)-mediated phosphorylation of SARM1 regulates NAD+ cleavage activity to inhibit mitochondrial respiration\|Here, we report that NAD+ cleavage activity of SARM1 is regulated by its own phosphorylation at serine 548. The phosphorylation of SARM1 was mediated by c-jun N-terminal kinase (JNK) under oxidative stress conditions, resulting in inhibition of mitochondrial respiration concomitant with enhanced activity of NAD+ cleavage. Nonphosphorylatable mutation of Ser-548 or treatment with a JNK inhibitor decreased SARM1 activity.	SIGNOR-275554
P53420	Q92626	0	catalytic activity	up-regulates quantity by stabilization	0.256	Peroxidasin (PXDN), an ECM protein with peroxidase activity, is integral to basement membrane consolidation through catalysis of sulfilimine bonds in collagen IV. PXDN has been shown to form dityrosine crosslinks and also catalyses sulfilimine bonds, in the presence of hypohalous acids, to connect collagen IV protomers, which are an integral component of the basement membrane	SIGNOR-265250
Q71DI3	Q9NRC8	0	deacetylation	up-regulates activity	0.2	SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation.\|Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression.	SIGNOR-275875
P01116	Q92565	0	guanine nucleotide exchange factor	up-regulates	0.436	Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.	SIGNOR-183735
Q9C0K0	Q9UPW6	0	transcriptional regulation	down-regulates quantity	0.495	Satb2 represses the transcription of Nr4a2. The misexpression of Nr4a2 together with Ctip2 induces expression of SubC-specific genes in wild-type Rsp, and simultaneous knockdown of these two genes in Rsp Satb2-mutant cells prevents their fate transition to SubC identity. Thus, Satb2 serves as a determinant gene in the Rsp regionalization by repressing Nr4a2 and Ctip2 during cortical development	SIGNOR-268931
Q9UQM7	P29475	1	phosphorylation	down-regulates activity	0.471	It was found that purified recombinant nNOS was phosphorylated by CaM-K Ialpha, CaM-K IIalpha, and CaM-K IV at Ser847 in vitro. Replacement of Ser847 with Ala (S847A) prevented phosphorylation by CaM kinases. Phosphorylated recombinant wild-type nNOS at Ser847 (approximately 0.5 mol of phosphate incorporation into nNOS) exhibited a 30% decrease of Vmax with little change of both the Km for L-arginine and Kact for CaM relative to unphosphorylated enzyme. The activity of mutant S847D was decreased to a level 50-60% as much as the wild-type enzyme. The decreased NOS enzyme activity of phosphorylated nNOS at Ser847 and mutant S847D was partially due to suppression of CaM binding, but not to impairment of dimer formation which is thought to be essential for enzyme activation.	SIGNOR-250635
P04150	P20962	0	transcriptional regulation	up-regulates quantity by expression	0.328	Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner	SIGNOR-268460
P24941	O94761	1	phosphorylation	up-regulates activity	0.329	During S/G2 phases, CDK1 and CDK2 (CDK1/2) phosphorylate RECQL4 on serines 89 and 251, enhancing MRE11/RECQL4 interaction and RECQL4 recruitment to DSBs.	SIGNOR-277374
Q14145	Q13501	0	ubiquitination	down-regulates quantity by destabilization	0.712	When autophagy is impaired, accumulated SQSTM1 interacts with KEAP1, leading to the proteasomal degradation of KEAP1. This interaction sequesters KEAP1 away from NFE2L2, preventing the ubiquitination and degradation of NFE2L2. Consequently, NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins.	SIGNOR-279849
P42768	P19784	0	phosphorylation	up-regulates activity	0.347	We identify two phosphorylation sites in the VCA domain of WASP at serines 483 and 484. S483 and S484 are substrates for casein kinase 2 in vitro and in vivo. Phosphorylation of these residues increases the affinity of the VCA domain for the Arp2/3 complex 7-fold and is required for efficient in vitro actin polymerization by the full-length WASP molecule.	SIGNOR-251048
P53350	Q14674	1	phosphorylation	down-regulates activity	0.772	Although mutation of serine 1126 and threonine 1346 to alanine had no effect (lanes 2 and 5), additional mutation of threonine 1363 and serine 1399 rendered separase almost completely resistant to phosphorylation (lane 3). Serine 1399 seems to be the one residue within this large separase fragment that is most efficiently phosphorylated by polo-like kinase, because a corresponding point mutation was sufficient to reduce the labeling by 80% compared with wild type (lane 6).	SIGNOR-276082
P15311	Q5S007	0	phosphorylation	up-regulates activity	0.411	LRRK2 also phosphorylated ezrin and radixin, which are related to moesin, at the residue equivalent to Thr558, as well as a peptide (LRRKtide: RLGRDKYKTLRQIRQ) encompassing Thr558.	SIGNOR-279202
P17612	P15056	1	phosphorylation	down-regulates activity	0.635	Direct phosphorylation of B-Raf by PKA exerts a negative effect on its kinase activity, essentially via phosphorylation of Ser429	SIGNOR-250339
Q13480	A7KAX9	1	relocalization	up-regulates	0.314	Gc-gap, a rho family gtpase-activating protein that interacts with signaling adapters gab1 and gab2.	SIGNOR-102586
O60260	O75385	0	phosphorylation	up-regulates activity	0.2	Furthermore, the Parkin band shift induced by catalytically active WT ULK1 was diminished by treatment of cell lysates with lambda-phosphatase, as was the mobility of ULK1 itself (XREF_FIG).\|Parkin is phosphorylated by ULK1 at Ser 108 in its recently described nine amino acid ACT element at this early time point	SIGNOR-279663
P40692	P04637	0	transcriptional regulation	up-regulates quantity	0.61	.... 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-257605
P62837	O95071	1	ubiquitination	up-regulates activity	0.508	Using an in vitro reconstitution, specific E2 (ubiquitin-conjugating) enzymes (human UbcH4, UbcH5B, and UbcH5C) transferred ubiquitin molecules to hHYD, leading to the ubiquitination of TopBP1. TopBP1 was usually ubiquitinated and degraded by the proteosome, whereas X-irradiation diminished the ubiquitination of TopBP1 probably via the phosphorylation, resulting in the stable colocalization of up-regulated TopBP1 with gamma-H2AX nuclear foci in DNA breaks.	SIGNOR-272668
Q8TB45	P27361	0	phosphorylation	up-regulates quantity by stabilization	0.282	Screening the DEPTOR interactome identified that the association of USP-7 deubiquitinase with DEPTOR was dependent upon S235 phosphorylation. Inhibition of USP-7 activity resulted in DEPTOR polyubiquitination and degradation. A scansite search suggested that ERK1 may be responsible for S235 phosphorylation, which was confirmed through the use of inhibitors, ERK1 knockdown, and an in vitro kinase assay.	SIGNOR-277587
Q09472	Q9UPU5	0	deubiquitination	up-regulates quantity by stabilization	0.271	In this study, several cancer-related proteins (Bax, p300, E2F4 and securin) have been proven to be substrates of ubiquitin-specific peptidase 24 (USP24), and relevance has been shown between USP24 and its substrates in samples from clinical lung cancer patients. \|Knockdown of USP24 decreases Bax and p300 levels	SIGNOR-275607
Q06124	P23458	0	phosphorylation	up-regulates activity	0.768	Tyrosine residues 304 and 327 in shp-2 are phosphorylated by jaks, and phosphorylated shp-2 can associate with the downstream adapter protein grb2	SIGNOR-236274
Q5MJ70	P24941	1	relocalization	up-regulates activity	0.791	Speedy/RINGO A, a noncanonical activator of CDK2, was recently identified as a key regulator for CDK2 recruitment to meiotic telomeres	SIGNOR-263310
P42226	P23771	1	null	up-regulates	0.662	GATA-3 plays a central role in regulating Th1 and Th2 cell differentiation. Upon interleukin (IL)-4 binding to its receptor, GATA-3 is induced through the action of Stat6	SIGNOR-254299
P48454	O95644	1	relocalization	up-regulates	0.704	The ca2+ dependent phosphatase calcineurin induces cardiac and skeletal muscle hypertrophy by a process that involves nf-at nuclear translocation, and activation of mef2c.	SIGNOR-179796
Q92934	Q15818	0	relocalization	up-regulates activity	0.2	Immunofluorescence staining and subcellular fractionation analyses revealed increased mitochondrial translocation of Bad and Bax proteins from cytoplasm following OGD (4 h) and simultaneously increased release of Cyt C from mitochondria followed by activation of caspase-3. NP1 protein was immunoprecipitated with Bad and Bax proteins; OGD caused increased interactions of NP1 with Bad and Bax, thereby, facilitating their mitochondrial translocation and dissipation of mitochondrial membrane potential	SIGNOR-261483
P24941	Q14207	1	phosphorylation	up-regulates	0.447	Importantly, mutation of cdk2 phosphorylation sites to alanine abrogates the ability of p220 to activate the histone h2b promoter.	SIGNOR-82141
O15297	O14757	1	dephosphorylation	down-regulates activity	0.473	Here we show that the oncogenic p53-induced serine/threonine phosphatase, PPM1D (or Wip1), dephosphorylates two ATM/ATR targets, Chk1 and p53. PPM1D binds Chk1 and dephosphorylates the ATR-targeted phospho-Ser 345, leading to decreased Chk1 kinase activity.	SIGNOR-248317
Q8WV28	Q9NRF2	0	dephosphorylation	down-regulates activity	0.2	SHP-1 is recruited by the phosphorylated ITIM-bearing receptors such as CD22 and it dephosphorylates proximal BCR signaling molecules such as CD79, SYK, BLNK.	SIGNOR-268446
P17844	P17252	0	phosphorylation	down-regulates activity	0.335	We report that p68 is phosphorylated by protein kinase C in vitro and binds calmodulin in a Ca(2+)-dependent manner. Both phosphorylation and calmodulin binding inhibited p68 ATPase activity \| In addition, a 20-amino acid peptide corresponding to residues 549-568 of p68 was phosphorylated in a Ca- and phospholipid-dependent manner hy PKC	SIGNOR-248896
P48729	P27348	1	phosphorylation	down-regulates activity	0.516	This protein kinase has been identified as casein kinase Ialpha (CKIalpha) by peptide mapping analysis and sequencing. Among mammalian 14-3-3, only 14-3-3 tau possesses a phosphorylatable residue at the same position (Ser-233), and we show that this residue is also phosphorylated by CKI. In addition, we show that 14-3-3 zeta is exclusively phosphorylated on Thr-233 in human embryonic kidney 293 cells. The residue 233 is located within a region shown to be important for the association of 14-3-3 to target proteins.	SIGNOR-250795
Q8TEV9	Q9Y4P8	1	transcriptional regulation	up-regulates quantity	0.271	Global mRNA expression analysis revealed that SMCR8 regulates transcription of several other autophagy genes including WIPI2	SIGNOR-252028
Q9NZI6	P06493	0	phosphorylation	up-regulates activity	0.2	In addition, overexpression of TFCP2L1 and CDK1 in T24 cells increased clonogenic activity in a clonogenic limiting dilution assay (Fig\u00a05H), confirming the importance of CDK1\u2010TFCP2L1 pathways for the stemness features of BC cells.High levels of co\u2010expression of p\u2010TFCP2L1 and CDK1 were associated with distant metastasis in our cohort of BC patients (Table\u00a01).\|Tfcp2l1 Thr177 phosphorylation by CDK1 is essential for proliferation and cell cycle progression of ESCs.\|Tfcp2l1 is phosphorylated at Thr177 by CDK1.	SIGNOR-278472
Q05682	P28482	0	phosphorylation	down-regulates	0.539	Extracellular signal-regulated kinases (erks) phosphorylate the high molecular mass isoform of the actin-binding protein caldesmon (h-cad) at two sites (ser(759) and ser(789)) during smooth muscle stimulation. Nmr spectroscopy shows that the actin binding properties of the minimal inhibitory region of caldesmon, residues 750-779, alter upon map kinase phosphorylation of ser-759, a residue not involved in actin binding. This phosphorylation leads to markedly diminished actin affinity as a result of the loss of interaction at one of the two sites that bind to f-actin.	SIGNOR-71037
P04637	Q92794	0	acetylation	up-regulates	0.67	We show here that moz is an acetyltransferase of p53 at k120 and k382 and colocalizes with p53 in promyelocytic leukemia (pml) nuclear bodies following cellular stress. The moz-pml-p53 interaction enhances moz-mediated acetylation of p53, and this ternary complex enhances p53-dependent p21 expression	SIGNOR-201486
Q99878	Q9Y4B6	0	phosphorylation	up-regulates activity	0.2	Here we report that VprBP possesses an intrinsic protein kinase activity and is capable of phosphorylating histone H2A on threonine 120 (H2AT120p) in a nucleosomal context. Functional studies reveal that H2AT120p by VprBP is sufficient to repress chromatin transcription.	SIGNOR-279884
Q8WUI4	Q9BZL6	0	phosphorylation	up-regulates activity	0.437	Histone deacetylase (HDAC) 5 and 7, two members of the class II of classical HDAC [62], are in vivo substrates of PKD3 and PKD [63]. In response to a variety of signals, including phorbol esters, T cell receptor engagement, vascular endothelial growth factor and angiotensin stimulation, the activity of HDAC5 and 7 are regulated by a mechanism that involves PKD3 and PKD-mediated phosphorylation of the highly conserved Ser259 and Ser498 residues that are located in N-terminus of class II HDACs [63–67].	SIGNOR-275933
P00533	P04083	1	phosphorylation	up-regulates	0.508	The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].Finally in 2013 caron et al. showed the relevance of y21 phosphorylation for the anxa1 stability. In fact the authors demonstrated that the tyrosine 21 phosphorylation is crucial for anxa1 sumoylation induced by egf	SIGNOR-202776
Q07890	P01116	1	guanine nucleotide exchange factor	up-regulates	0.713	Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85.	SIGNOR-175265
P28482	P06401	1	phosphorylation	down-regulates	0.605	Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26s proteasome	SIGNOR-74712
P41162	Q9UHI6	1	transcriptional regulation	down-regulates quantity by repression	0.739	ETV3 target genes including etv3, ddx20, and dusp6 provide negative feedback regulation of ETV3 production and activity. Negative feedback along with constitutive instability may serve to tightly regulate ETV3 abundance. Our date suggest that phosphorylation by ERK2 relieves repression by ETV3, allowing activation of cell cycle control genes including myc, components of the NF-κB pathway, and genes required form RNA processing and translation.	SIGNOR-262779
O95714	P38398	1	ubiquitination	down-regulates quantity by destabilization	0.561	HERC2 ubiquitinates BRCA1; this reaction depends on Cys(4762) of HERC2, the catalytic ubiquitin binding site, and the degron of BRCA1.\|Significantly, HERC2 depletion antagonizes the effects of BARD1 depletion by restoring BRCA1 expression and G(2)-M checkpoint activity.	SIGNOR-278813
P29590	P78317	0	polyubiquitination	down-regulates quantity by destabilization	0.487	Upon TGF-β induction, interaction of Arkadia with phosphorylated Smad2 triggers degradation of SnoN, whereas upon arsenic treatment, interaction of Arkadia with poly-SUMO in PML nuclear bodies induces degradation of polysumoylated PML together with RNF4.	SIGNOR-272884
P08913	P25098	0	phosphorylation	down-regulates activity	0.2	The alpha 2A-adrenergic receptor (alpha 2AAR) undergoes rapid functional desensitization caused by phosphorylation of the receptor by the beta-adrenergic receptor kinase (beta ARK). beta ARK-mediated phosphorylation of alpha 2C10 occurs at Ser-296-299 in the third intracellular loop, and this represents the critical step in rapid agonist-promoted desensitization.	SIGNOR-251440
Q8N122	P42345	0	phosphorylation	up-regulates activity	0.989	The phosphorylation of raptor is stimulated by insulin and inhibited by rapamycin. Importantly, the site-directed mutation of raptor at one phosphorylation site, Ser(863), reduced mTORC1 activity both in vitro and in vivo.	SIGNOR-184959
Q96FA3	Q13489	1	ubiquitination	up-regulates quantity by stabilization	0.455	Notably, Pellino-1 directly interacted with cIAP2 and stabilized cIAP2 through lysine63-mediated polyubiquitination via its E3 ligase activity.	SIGNOR-259395
P43405	P30307	1	phosphorylation	down-regulates activity	0.36	SYK Phosphorylates CDC25C on Serine 216.\|We now provide new genetic and biochemical evidence that SYK is an inhibitor of CDC25C in B-lineage lymphoid cells as well as non lymphohematopoietic cells, that prevents premature entry into mitosis by phosphorylating CDC25C at S216 when G 2 checkpoint responses are activated.	SIGNOR-278328
P12931	P24666	0	dephosphorylation	up-regulates activity	0.438	LMWPTP dephosphorylated pY(527)-Src and pY(416)-Src in vitro, with greater specificity for pY(527)Src. Activation of LMWPTP produced strong activation of Src mediated by fast dephosphorylation of pY(527)-Src, followed by slower deactivation of this kinase via dephosphorylation of pY(416)Src.	SIGNOR-248454
P00533	Q7Z699	1	phosphorylation	down-regulates activity	0.272	We show that oncogenic EGFR(L858R) signaling leads to the phosphorylation of SPRED1 on serine 105, disrupting the SPRED1-neurofibromin complex. The structural, biochemical, and biological results provide new mechanistic insights about how SPRED1 interacts with neurofibromin and regulates active KRAS levels in normal and pathologic conditions.	SIGNOR-273638
P07948	P12318	1	phosphorylation	up-regulates activity	0.608	Phosphorylation of FcgammaRIIa/c by Lyn is clearly dependent on the presence of Y-298, since all mutants lacking this residue are not phosphorylated by this PTK. This result suggests that Y-298 might be the only tyrosine residue of FcgammaRIIa/c phos- phorylated by Lyn.	SIGNOR-249379
O14544	P10721	1	ubiquitination	down-regulates	0.678	Suppressor of cytokine signaling 6 (socs6) is a member of the socs family of e3 ubiquitin ligases that can interact with c-kit and suppress c-kit-dependent pathways. / we demonstrate that socs6 has ubiquitin ligase activity toward c-kit and regulates c-kit protein turnover in cells	SIGNOR-169145
Q15154	Q86YT6	0	ubiquitination	down-regulates	0.371	We demonstrate that the E3 ubiquitin ligase MIB1 is a new component of centriolar satellites, which interacts with and ubiquitylates AZI1 and PCM1 and suppresses primary cilium formation.	SIGNOR-272878
P33981	P24941	0	phosphorylation	up-regulates quantity by stabilization	0.411	Cdk2 phosphorylates Mps1 at T468, attenuating the function of a degradation signal found in amino acids 420\u2013507 (encoded by exons 12 and 13) and allowing the accumulation of a centrosomal pool of Mps1 that represents no more than 10% of total cellular Mps1 ( xref ).	SIGNOR-279398
Q9Y613	Q13976	0	phosphorylation	up-regulates	0.354	Pkgi also directly phosphorylates fhod1, and studies with wild-type and mutant fhod1-derived peptides identify ser-1131 in the fhod1 c terminus as the unique pkgi phosphorylation site in fhod1. phosphorylation of three conserved residues within the dad domain activates fhod1 while binding to rac regulates fhod1 subcellular localization	SIGNOR-123646
Q07869	P27361	0	phosphorylation	up-regulates activity	0.601	We now demonstrate that amino acids 1-92 of hPPARalpha contain an activation function (AF)-1-like domain, which is further activated by insulin through a pathway involving the mitogen-activated protein kinases p42 and p44. Further analysis of the amino-terminal region of PPARalpha revealed that the insulin-induced trans-activation occurs through the phosphorylation of two mitogen-activated protein kinase sites at positions 12 and 21, both of which are conserved across evolution.	SIGNOR-249474
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
Q00535	Q12879	1	phosphorylation	up-regulates activity	0.525	Here, we demonstrate that cyclin dependent kinase-5 (Cdk5) associates with and phosphorylates NR2A subunits at Ser-1232 in vitro and in intact cells. Moreover, we show that roscovitine, a selective Cdk5 inhibitor, blocks both long-term potentiation induction and NMDA-evoked currents in rat CA1 hippocampal neurons. These results suggest that Cdk5 plays a key role in synaptic transmission and plasticity through its up-regulation of NMDARs.	SIGNOR-250666
Q9HAU4	P37173	1	ubiquitination	down-regulates activity	0.595	Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps.	SIGNOR-195681
Q01860	Q96GD4	0	phosphorylation	down-regulates activity	0.38	Aurkb phosphorylates Oct4(S229) during G2/M phase, leading to the dissociation of Oct4 from chromatin, whereas PP1 binds Oct4 and dephosphorylates Oct4(S229) during M/G1 transition, which resets Oct4-driven transcription for pluripotency and the cell cycle.	SIGNOR-279592
Q8NG66	O14757	0	phosphorylation	up-regulates	0.264	We demonstrate that chk1 (checkpoint kinase 1) directly activates nek11 by phosphorylating it on ser 273	SIGNOR-187863
Q9UKV5	Q14258	0	polyubiquitination	down-regulates quantity by destabilization	0.364	We further demonstrate that TRIM25 ubiquitylates gp78 and that overexpression of TRIM25 accelerates the degradation of gp78. Our data suggest that TRIM25 not only cooperates with gp78 in polyubiquitylation of AMF but also gauges the steady-state level of gp78.	SIGNOR-272176
P45983	O14733	0	phosphorylation	up-regulates	0.699	Jnk is activated by jnk-activating kinase 1 (jnkk1), a dual specificity protein kinase that phosphorylates jnk on threonine 183 and tyrosine 185 residues.	SIGNOR-51199
P68400	P05455	1	phosphorylation	up-regulates	0.337	Prior studies indicate that hla is activated by phosphorylation of serine-366 by protein kinase ck2, neutralizing a negative effect of a short basic motif (sbm)	SIGNOR-160761
P09758	Q05655	0	phosphorylation	down-regulates activity	0.2	Analyses using HCT116 cells expressing WT Trop-2 (HCT116/WT) or Trop-2 alanine-substituted at Ser-303 (HCT116/S303A) or Ser-322 (HCT116/S322A) revealed that Trop-2 is phosphorylated at Ser-322. sing protein kinase C (PKC) inhibitors and PKC-specific siRNAs, we found that PKCα and PKCδ are responsible for Trop-2 phosphorylation.	SIGNOR-273820
Q08881	P51813	1	phosphorylation	up-regulates activity	0.334	Itk phosphorylated Bmx-SH3 to a low extent. pY positions correspond to the residues Y215 and Y223 in Bmx. Tec family protein tyrosine kinases (TFKs) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop.	SIGNOR-251331
Q8N6T7	P01375	1	deacetylation	up-regulates	0.314	Sirt6 regulates tnf-alfa secretion through hydrolysis of long-chain fatty acyl lysine	SIGNOR-201662
Q99683	O14548	1	phosphorylation	up-regulates activity	0.2	Phosphorylation of EB1 by ASK1 promotes the binding of EB1 to CLIP-170 and p150 glued.	SIGNOR-278341
Q04771	Q15797	1	phosphorylation	up-regulates activity	0.703	ALK2 receptor specifically interacts with and phosphorylates Smad1 protein. ALK2 Activates Smad1 and Induces BMP-specific Signals. Biochemical analysis revealed that constitutively active ALK2 associated with and phosphorylated Smad1 on the COOH-terminal SSXS motif	SIGNOR-251439
Q13541	P49674	0	phosphorylation	down-regulates	0.2	Mechanistic investigations showed that ck1_ interacted with and phosphorylated 4e-bp1 at two novel sites t41 and t50, which were essential for 4e-bp1 inactivation along with increased mrna translation and cell proliferation.	SIGNOR-203240
P49841	P41236	1	phosphorylation	up-regulates activity	0.412	Protein phosphatase 1 (PP1) is complexed with inhibitor 2 (I-2) in the cytosol. In rabbit muscle extract PP1.I-2 is activated upon preincubation with ATP/Mg. This activation is caused by phosphorylation of I-2 on Thr(72) by glycogen synthase kinase 3 (GSK3).	SIGNOR-251257
P84243	Q15418	0	phosphorylation	down-regulates activity	0.2	Phosphorylation at ser-11 (h3s10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or uv irradiation and result in the activation of genes, such as c-fos and c-jun.	SIGNOR-70428
P17655	P49841	1	cleavage	up-regulates activity	0.285	Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase	SIGNOR-251613
P01215	P50458	0	transcriptional regulation	up-regulates quantity by expression	0.266	In Cos cells, LH-2 activated the a-subunit promoter approximately twofold	SIGNOR-266055
Q02156	P28329	1	phosphorylation	up-regulates	0.312	We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation	SIGNOR-129312
Q9NRA0	Q96PU5	0	ubiquitination	down-regulates quantity by destabilization	0.2	In this study, we found that NEDD4L interacted with SphK2 to ubiquitinate SphK2 protein.\|NEDD4L Mediates the Degradation of SphK2 Protein Through the Ubiquitin-Proteasomal Pathway.	SIGNOR-278660
Q13627	Q8IXJ6	1	phosphorylation	up-regulates activity	0.293	This Minibrain/Dyrk1a kinase phosphorylates and activates the Silent information regulator 2/Sirtuin1 deacetylase, which in turn deacetylates and activates the FOXO transcription factor.	SIGNOR-279990

P04637

Q8IW41

0

phosphorylation

up-regulates

0.76

Furthermore, we show that prak activates p53 by direct phosphorylation. prak phosphorylates p53 at ser37

SIGNOR-152847

P17676

P35638

0

transcriptional regulation

down-regulates quantity

0.668

We find that expression of CHOP, a nuclear protein that dimerizes avidly with C/EBP isoforms alpha and beta and directs the resulting heterodimer away from classic C/EBP-binding sites, markedly inhibits this differentiation process.

SIGNOR-255914

P52597

Q96JP5

0

ubiquitination

down-regulates quantity

0.2

Collectively, our results indicate that ZFP91 polyubiquitinated hnRNP F at Lys 185.|We found that silencing ZFP91 increased hnRNP F protein levels, but not hnRNP F mRNA levels, while ectopically expressing ZFP91 decreased hnRNP F protein levels, but not hnRNP F mRNA levels.

SIGNOR-278802

Q00534

P19532

1

phosphorylation

up-regulates activity

0.2

CDK4 and CDK6 interact with TFEB and TFE3 in the nucleus We next investigated how CDK4 and CDK6 activate TFEB and TFE3 .|CDK4 and CDK6 phosphorylate TFEB and TFE3.

SIGNOR-279517

Q5SQI0

Q71U36

1

acetylation

up-regulates quantity by stabilization

0.268

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

SIGNOR-272251

Q15120

P08559

1

phosphorylation

down-regulates activity

0.871

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

SIGNOR-109647

Q86WV6

O43318

0

phosphorylation

up-regulates activity

0.2

Activated TAK1 directly mediates STING phosphorylation on serine 355, which facilitates its interaction with STING ER exit protein (STEEP) and thereby promotes its oligomerization and translocation to the ERGIC for subsequent activation

SIGNOR-277887

Q96SB4

Q07955

1

phosphorylation

up-regulates

0.799

These results suggest that the formation of complexes between sf2/asf and srpks, which is influenced by the phosphorylation state of sf2/asf, may have regulatory roles in the assembly and localization of this splicing factor.

SIGNOR-66465

P61586

B2RTY4

0

gtpase-activating protein

down-regulates activity

0.565

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-260508

Q13555

Q15746

1

phosphorylation

down-regulates activity

0.331

Phosphorylation of MLC kinase by CaM protein kinase II increased the dissociation constant of MLC kinase for calmodulin about 10 times without changing the Vmax. The location of the phosphorylation sites was identified by isolating and sequencing the tryptic phosphopeptides of MLC kinase. The preferred site was identified as serine 512 and the second site as serine 525. These sites are the same as the sites phosphorylated by cAMP-dependent protein kinase.

SIGNOR-250700

P35611

P17612

0

phosphorylation

down-regulates activity

0.311

Protein kinase A phosphorylates -adducin at three sites in the neck domain (Ser-408, ’436, and ’481) in addition to the MARCKS-related domain of both subunits. Phosphorylation by PKA, in contrast to PKC, reduced affinity of erythrocyte adducin for spectrin-F-actin complexes as well as activity of adducin in promoting binding of spectrin to F-actin.

SIGNOR-250331

P00746

P00751

1

cleavage

up-regulates activity

0.804

The resulting proconvertase C3bB is subsequently cleaved by factor D (FD), generating the AP C3 convertase C3bBb

SIGNOR-263488

Q96CF2

Q6PHR2

0

phosphorylation

down-regulates activity

0.286

CHMP4C was phosphorylated by recombinant ULK3 in these experiments, whereas CHMP4A and CHMP4B were not (Figure 7\u2014figure supplement 1A).

SIGNOR-279771

P29966

Q16512

0

phosphorylation

down-regulates activity

0.365

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

SIGNOR-249671

P08559

Q13131

0

phosphorylation

up-regulates activity

0.2

AMPKα phosphorylates PDHA subunit on Ser295 and Ser314 to activate PDH complex

SIGNOR-276837

P53567

Q9NPD5

1

transcriptional regulation

up-regulates quantity by expression

0.2

Taken together, these findings suggest that the LPS-induced down-regulation of Oatp4 is likely due to reduction in the binding of HNF1alpha, C/EBP, HNF3, and RXR:RAR to the Oatp4 promoter.

SIGNOR-268986

Q96CG3

O14965

0

phosphorylation

up-regulates activity

0.2

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

SIGNOR-273551

Q9ULU4

P00533

1

transcriptional regulation

down-regulates quantity by repression

0.2

Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported

SIGNOR-262040

Q9H0A0

P09874

1

acetylation

up-regulates quantity by stabilization

0.2

MORC2 directly interacts with PARP1. MORC2 mediates the interaction between PARP1 and NAT10 and thereby promotes NAT10-mediated PARP1 acetylation at K949, which blocks CHFR-mediated ubiquitination and degradation of PARP1.

SIGNOR-273715

P29350

Q13237

0

phosphorylation

up-regulates activity

0.2

PKGII directly phosphorylated and stimulated SHP-1 activity

SIGNOR-276288

P25054

O60566

0

phosphorylation

up-regulates activity

0.428

These findings support a model in which BubR1 kinase may directly regulate APC function involved in stable kinetochore microtubule attachment.|Using purified components, BubR1 directly phosphorylates APC and forms a ternary complex with APC and microtubules.

SIGNOR-279393

Q14721

P12931

0

phosphorylation

up-regulates

0.479

In the present study we show that an n-terminal tyrosine of kv2.1 (y124), which is a known target of src kinase, is critical for the apoptotic current surge..Kv2.1-mediated k+ currents are also enhanced during non-injurious conditions through direct phosphorylation of intracellular n-terminal residue tyrosine 124 (y124) by src kinase

SIGNOR-187201

Q13131

O95863

1

phosphorylation

up-regulates quantity by stabilization

0.2

Serines 11 and 92 participate in the control of snail1 stability and positively regulate snail1 repressive function and its interaction with msin3a corepressor. Furthermore, serines 11 and 92 are required for snail1-mediated emt and cell viability, respectively. Pka and ck2 have been characterized as the main kinases responsible for in vitro snail1 phosphorylation at serine 11 and 92, respectively.

SIGNOR-161779

Q96GD4

Q8NG31

1

phosphorylation

down-regulates

0.2

To determine whether the combinatorial regulation of the kmn network by aurora b observed in vitro is critical to controlling kinetochore-microtubule attachments in vivo, we next investigated the effect of the phosphomimetic (to aspartate) and nonphosphorylatable (to alanine) mutants of dsn1, knl1, and ndc80 in vertebrate cells. We predicted that both types of mutations in critical phosphorylation sites would affect chromosome segregation, since preventing the inactivation of inappropriately attached kinetochores by aurora b (in the nonphosphorylatable mutant) or constitutively inactivating this attachment (in the phosphomimetic mutant).

SIGNOR-165502

P42574

P49768

1

cleavage

up-regulates activity

0.454

Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.

SIGNOR-261756

P17612

Q13085

1

phosphorylation

down-regulates activity

0.2

TC1 = Ser-2Ser(P)-Met-3Ser(P)-Gly-Leu; TC2 = Arg-Met-1Ser(P)-Phe- Cyclic-AMP-dependent protein kinase phosphorylates sites 1 and 2 exclusively, whereas the AMP-activated protein kinase phosphorylates sites 1 and 3, plus at least one other minor site.[…]The results suggest that phosphorylation of site 3 is primarily responsible for the large decrease in Vmax produced by the AMP-activated protein kinase, while phosphorylation of site 1 may be primarily responsible for the increase in A0.5 for citrate and more modest depression of Vmax produced by cyclic-AMP-dependent protein kinase and ACK2

SIGNOR-267714

P45983

Q6SZW1

1

phosphorylation

down-regulates activity

0.423

C-Jun N-terminal kinase (JNK)-mediated phosphorylation of SARM1 regulates NAD+ cleavage activity to inhibit mitochondrial respiration|Here, we report that NAD+ cleavage activity of SARM1 is regulated by its own phosphorylation at serine 548. The phosphorylation of SARM1 was mediated by c-jun N-terminal kinase (JNK) under oxidative stress conditions, resulting in inhibition of mitochondrial respiration concomitant with enhanced activity of NAD+ cleavage. Nonphosphorylatable mutation of Ser-548 or treatment with a JNK inhibitor decreased SARM1 activity.

SIGNOR-275554

P53420

Q92626

0

catalytic activity

up-regulates quantity by stabilization

0.256

Peroxidasin (PXDN), an ECM protein with peroxidase activity, is integral to basement membrane consolidation through catalysis of sulfilimine bonds in collagen IV. PXDN has been shown to form dityrosine crosslinks and also catalyses sulfilimine bonds, in the presence of hypohalous acids, to connect collagen IV protomers, which are an integral component of the basement membrane

SIGNOR-265250

Q71DI3

Q9NRC8

0

deacetylation

up-regulates activity

0.2

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

SIGNOR-275875

P01116

Q92565

0

guanine nucleotide exchange factor

up-regulates

0.436

Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.

SIGNOR-183735

Q9C0K0

Q9UPW6

0

transcriptional regulation

down-regulates quantity

0.495

Satb2 represses the transcription of Nr4a2. The misexpression of Nr4a2 together with Ctip2 induces expression of SubC-specific genes in wild-type Rsp, and simultaneous knockdown of these two genes in Rsp Satb2-mutant cells prevents their fate transition to SubC identity. Thus, Satb2 serves as a determinant gene in the Rsp regionalization by repressing Nr4a2 and Ctip2 during cortical development

SIGNOR-268931

Q9UQM7

P29475

1

phosphorylation

down-regulates activity

0.471

It was found that purified recombinant nNOS was phosphorylated by CaM-K Ialpha, CaM-K IIalpha, and CaM-K IV at Ser847 in vitro. Replacement of Ser847 with Ala (S847A) prevented phosphorylation by CaM kinases. Phosphorylated recombinant wild-type nNOS at Ser847 (approximately 0.5 mol of phosphate incorporation into nNOS) exhibited a 30% decrease of Vmax with little change of both the Km for L-arginine and Kact for CaM relative to unphosphorylated enzyme. The activity of mutant S847D was decreased to a level 50-60% as much as the wild-type enzyme. The decreased NOS enzyme activity of phosphorylated nNOS at Ser847 and mutant S847D was partially due to suppression of CaM binding, but not to impairment of dimer formation which is thought to be essential for enzyme activation.

SIGNOR-250635

P04150

P20962

0

transcriptional regulation

up-regulates quantity by expression

0.328

Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner

SIGNOR-268460

P24941

O94761

1

phosphorylation

up-regulates activity

0.329

During S/G2 phases, CDK1 and CDK2 (CDK1/2) phosphorylate RECQL4 on serines 89 and 251, enhancing MRE11/RECQL4 interaction and RECQL4 recruitment to DSBs.

SIGNOR-277374

Q14145

Q13501

0

ubiquitination

down-regulates quantity by destabilization

0.712

When autophagy is impaired, accumulated SQSTM1 interacts with KEAP1, leading to the proteasomal degradation of KEAP1. This interaction sequesters KEAP1 away from NFE2L2, preventing the ubiquitination and degradation of NFE2L2. Consequently, NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins.

SIGNOR-279849

P42768

P19784

0

phosphorylation

up-regulates activity

0.347

We identify two phosphorylation sites in the VCA domain of WASP at serines 483 and 484. S483 and S484 are substrates for casein kinase 2 in vitro and in vivo. Phosphorylation of these residues increases the affinity of the VCA domain for the Arp2/3 complex 7-fold and is required for efficient in vitro actin polymerization by the full-length WASP molecule.

SIGNOR-251048

P53350

Q14674

1

phosphorylation

down-regulates activity

0.772

Although mutation of serine 1126 and threonine 1346 to alanine had no effect (lanes 2 and 5), additional mutation of threonine 1363 and serine 1399 rendered separase almost completely resistant to phosphorylation (lane 3). Serine 1399 seems to be the one residue within this large separase fragment that is most efficiently phosphorylated by polo-like kinase, because a corresponding point mutation was sufficient to reduce the labeling by 80% compared with wild type (lane 6).

SIGNOR-276082

P15311

Q5S007

0

phosphorylation

up-regulates activity

0.411

LRRK2 also phosphorylated ezrin and radixin, which are related to moesin, at the residue equivalent to Thr558, as well as a peptide (LRRKtide: RLGRDKYKTLRQIRQ) encompassing Thr558.

SIGNOR-279202

P17612

P15056

1

phosphorylation

down-regulates activity

0.635

Direct phosphorylation of B-Raf by PKA exerts a negative effect on its kinase activity, essentially via phosphorylation of Ser429

SIGNOR-250339

Q13480

A7KAX9

1

relocalization

up-regulates

0.314

Gc-gap, a rho family gtpase-activating protein that interacts with signaling adapters gab1 and gab2.

SIGNOR-102586

O60260

O75385

0

phosphorylation

up-regulates activity

0.2

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

SIGNOR-279663

P40692

P04637

0

transcriptional regulation

up-regulates quantity

0.61

.... 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-257605

P62837

O95071

1

ubiquitination

up-regulates activity

0.508

Using an in vitro reconstitution, specific E2 (ubiquitin-conjugating) enzymes (human UbcH4, UbcH5B, and UbcH5C) transferred ubiquitin molecules to hHYD, leading to the ubiquitination of TopBP1. TopBP1 was usually ubiquitinated and degraded by the proteosome, whereas X-irradiation diminished the ubiquitination of TopBP1 probably via the phosphorylation, resulting in the stable colocalization of up-regulated TopBP1 with gamma-H2AX nuclear foci in DNA breaks.

SIGNOR-272668

Q8TB45

P27361

0

phosphorylation

up-regulates quantity by stabilization

0.282

Screening the DEPTOR interactome identified that the association of USP-7 deubiquitinase with DEPTOR was dependent upon S235 phosphorylation. Inhibition of USP-7 activity resulted in DEPTOR polyubiquitination and degradation. A scansite search suggested that ERK1 may be responsible for S235 phosphorylation, which was confirmed through the use of inhibitors, ERK1 knockdown, and an in vitro kinase assay.

SIGNOR-277587

Q09472

Q9UPU5

0

deubiquitination

up-regulates quantity by stabilization

0.271

In this study, several cancer-related proteins (Bax, p300, E2F4 and securin) have been proven to be substrates of ubiquitin-specific peptidase 24 (USP24), and relevance has been shown between USP24 and its substrates in samples from clinical lung cancer patients. |Knockdown of USP24 decreases Bax and p300 levels

SIGNOR-275607

Q06124

P23458

0

phosphorylation

up-regulates activity

0.768

Tyrosine residues 304 and 327 in shp-2 are phosphorylated by jaks, and phosphorylated shp-2 can associate with the downstream adapter protein grb2

SIGNOR-236274

Q5MJ70

P24941

1

relocalization

up-regulates activity

0.791

Speedy/RINGO A, a noncanonical activator of CDK2, was recently identified as a key regulator for CDK2 recruitment to meiotic telomeres

SIGNOR-263310

P42226

P23771

1

null

up-regulates

0.662

GATA-3 plays a central role in regulating Th1 and Th2 cell differentiation. Upon interleukin (IL)-4 binding to its receptor, GATA-3 is induced through the action of Stat6

SIGNOR-254299

P48454

O95644

1

relocalization

up-regulates

0.704

The ca2+ dependent phosphatase calcineurin induces cardiac and skeletal muscle hypertrophy by a process that involves nf-at nuclear translocation, and activation of mef2c.

SIGNOR-179796

Q92934

Q15818

0

relocalization

up-regulates activity

0.2

Immunofluorescence staining and subcellular fractionation analyses revealed increased mitochondrial translocation of Bad and Bax proteins from cytoplasm following OGD (4 h) and simultaneously increased release of Cyt C from mitochondria followed by activation of caspase-3. NP1 protein was immunoprecipitated with Bad and Bax proteins; OGD caused increased interactions of NP1 with Bad and Bax, thereby, facilitating their mitochondrial translocation and dissipation of mitochondrial membrane potential

SIGNOR-261483

P24941

Q14207

1

phosphorylation

up-regulates

0.447

Importantly, mutation of cdk2 phosphorylation sites to alanine abrogates the ability of p220 to activate the histone h2b promoter.

SIGNOR-82141

O15297

O14757

1

dephosphorylation

down-regulates activity

0.473

Here we show that the oncogenic p53-induced serine/threonine phosphatase, PPM1D (or Wip1), dephosphorylates two ATM/ATR targets, Chk1 and p53. PPM1D binds Chk1 and dephosphorylates the ATR-targeted phospho-Ser 345, leading to decreased Chk1 kinase activity.

SIGNOR-248317

Q8WV28

Q9NRF2

0

dephosphorylation

down-regulates activity

0.2

SHP-1 is recruited by the phosphorylated ITIM-bearing receptors such as CD22 and it dephosphorylates proximal BCR signaling molecules such as CD79, SYK, BLNK.

SIGNOR-268446

P17844

P17252

0

phosphorylation

down-regulates activity

0.335

We report that p68 is phosphorylated by protein kinase C in vitro and binds calmodulin in a Ca(2+)-dependent manner. Both phosphorylation and calmodulin binding inhibited p68 ATPase activity | In addition, a 20-amino acid peptide corresponding to residues 549-568 of p68 was phosphorylated in a Ca- and phospholipid-dependent manner hy PKC

SIGNOR-248896

P48729

P27348

1

phosphorylation

down-regulates activity

0.516

This protein kinase has been identified as casein kinase Ialpha (CKIalpha) by peptide mapping analysis and sequencing. Among mammalian 14-3-3, only 14-3-3 tau possesses a phosphorylatable residue at the same position (Ser-233), and we show that this residue is also phosphorylated by CKI. In addition, we show that 14-3-3 zeta is exclusively phosphorylated on Thr-233 in human embryonic kidney 293 cells. The residue 233 is located within a region shown to be important for the association of 14-3-3 to target proteins.

SIGNOR-250795

Q8TEV9

Q9Y4P8

1

transcriptional regulation

up-regulates quantity

0.271

Global mRNA expression analysis revealed that SMCR8 regulates transcription of several other autophagy genes including WIPI2

SIGNOR-252028

Q9NZI6

P06493

0

phosphorylation

up-regulates activity

0.2

In addition, overexpression of TFCP2L1 and CDK1 in T24 cells increased clonogenic activity in a clonogenic limiting dilution assay (Fig\u00a05H), confirming the importance of CDK1\u2010TFCP2L1 pathways for the stemness features of BC cells.High levels of co\u2010expression of p\u2010TFCP2L1 and CDK1 were associated with distant metastasis in our cohort of BC patients (Table\u00a01).|Tfcp2l1 Thr177 phosphorylation by CDK1 is essential for proliferation and cell cycle progression of ESCs.|Tfcp2l1 is phosphorylated at Thr177 by CDK1.

SIGNOR-278472

Q05682

P28482

0

phosphorylation

down-regulates

0.539

Extracellular signal-regulated kinases (erks) phosphorylate the high molecular mass isoform of the actin-binding protein caldesmon (h-cad) at two sites (ser(759) and ser(789)) during smooth muscle stimulation. Nmr spectroscopy shows that the actin binding properties of the minimal inhibitory region of caldesmon, residues 750-779, alter upon map kinase phosphorylation of ser-759, a residue not involved in actin binding. This phosphorylation leads to markedly diminished actin affinity as a result of the loss of interaction at one of the two sites that bind to f-actin.

SIGNOR-71037

P04637

Q92794

0

acetylation

up-regulates

0.67

We show here that moz is an acetyltransferase of p53 at k120 and k382 and colocalizes with p53 in promyelocytic leukemia (pml) nuclear bodies following cellular stress. The moz-pml-p53 interaction enhances moz-mediated acetylation of p53, and this ternary complex enhances p53-dependent p21 expression

SIGNOR-201486

Q99878

Q9Y4B6

0

phosphorylation

up-regulates activity

0.2

Here we report that VprBP possesses an intrinsic protein kinase activity and is capable of phosphorylating histone H2A on threonine 120 (H2AT120p) in a nucleosomal context. Functional studies reveal that H2AT120p by VprBP is sufficient to repress chromatin transcription.

SIGNOR-279884

Q8WUI4

Q9BZL6

0

phosphorylation

up-regulates activity

0.437

Histone deacetylase (HDAC) 5 and 7, two members of the class II of classical HDAC [62], are in vivo substrates of PKD3 and PKD [63]. In response to a variety of signals, including phorbol esters, T cell receptor engagement, vascular endothelial growth factor and angiotensin stimulation, the activity of HDAC5 and 7 are regulated by a mechanism that involves PKD3 and PKD-mediated phosphorylation of the highly conserved Ser259 and Ser498 residues that are located in N-terminus of class II HDACs [63–67].

SIGNOR-275933

P00533

P04083

1

phosphorylation

up-regulates

0.508

The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].Finally in 2013 caron et al. showed the relevance of y21 phosphorylation for the anxa1 stability. In fact the authors demonstrated that the tyrosine 21 phosphorylation is crucial for anxa1 sumoylation induced by egf

SIGNOR-202776

Q07890

P01116

1

guanine nucleotide exchange factor

up-regulates

0.713

Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85.

SIGNOR-175265

P28482

P06401

1

phosphorylation

down-regulates

0.605

Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26s proteasome

SIGNOR-74712

P41162

Q9UHI6

1

transcriptional regulation

down-regulates quantity by repression

0.739

ETV3 target genes including etv3, ddx20, and dusp6 provide negative feedback regulation of ETV3 production and activity. Negative feedback along with constitutive instability may serve to tightly regulate ETV3 abundance. Our date suggest that phosphorylation by ERK2 relieves repression by ETV3, allowing activation of cell cycle control genes including myc, components of the NF-κB pathway, and genes required form RNA processing and translation.

SIGNOR-262779

O95714

P38398

1

ubiquitination

down-regulates quantity by destabilization

0.561

HERC2 ubiquitinates BRCA1; this reaction depends on Cys(4762) of HERC2, the catalytic ubiquitin binding site, and the degron of BRCA1.|Significantly, HERC2 depletion antagonizes the effects of BARD1 depletion by restoring BRCA1 expression and G(2)-M checkpoint activity.

SIGNOR-278813

P29590

P78317

0

polyubiquitination

down-regulates quantity by destabilization

0.487

Upon TGF-β induction, interaction of Arkadia with phosphorylated Smad2 triggers degradation of SnoN, whereas upon arsenic treatment, interaction of Arkadia with poly-SUMO in PML nuclear bodies induces degradation of polysumoylated PML together with RNF4.

SIGNOR-272884

P08913

P25098

0

phosphorylation

down-regulates activity

0.2

The alpha 2A-adrenergic receptor (alpha 2AAR) undergoes rapid functional desensitization caused by phosphorylation of the receptor by the beta-adrenergic receptor kinase (beta ARK). beta ARK-mediated phosphorylation of alpha 2C10 occurs at Ser-296-299 in the third intracellular loop, and this represents the critical step in rapid agonist-promoted desensitization.

SIGNOR-251440

Q8N122

P42345

0

phosphorylation

up-regulates activity

0.989

The phosphorylation of raptor is stimulated by insulin and inhibited by rapamycin. Importantly, the site-directed mutation of raptor at one phosphorylation site, Ser(863), reduced mTORC1 activity both in vitro and in vivo.

SIGNOR-184959

Q96FA3

Q13489

1

ubiquitination

up-regulates quantity by stabilization

0.455

Notably, Pellino-1 directly interacted with cIAP2 and stabilized cIAP2 through lysine63-mediated polyubiquitination via its E3 ligase activity.

SIGNOR-259395

P43405

P30307

1

phosphorylation

down-regulates activity

0.36

SYK Phosphorylates CDC25C on Serine 216.|We now provide new genetic and biochemical evidence that SYK is an inhibitor of CDC25C in B-lineage lymphoid cells as well as non lymphohematopoietic cells, that prevents premature entry into mitosis by phosphorylating CDC25C at S216 when G 2 checkpoint responses are activated.

SIGNOR-278328

P12931

P24666

0

dephosphorylation

up-regulates activity

0.438

LMWPTP dephosphorylated pY(527)-Src and pY(416)-Src in vitro, with greater specificity for pY(527)Src. Activation of LMWPTP produced strong activation of Src mediated by fast dephosphorylation of pY(527)-Src, followed by slower deactivation of this kinase via dephosphorylation of pY(416)Src.

SIGNOR-248454

P00533

Q7Z699

1

phosphorylation

down-regulates activity

0.272

We show that oncogenic EGFR(L858R) signaling leads to the phosphorylation of SPRED1 on serine 105, disrupting the SPRED1-neurofibromin complex. The structural, biochemical, and biological results provide new mechanistic insights about how SPRED1 interacts with neurofibromin and regulates active KRAS levels in normal and pathologic conditions.

SIGNOR-273638

P07948

P12318

1

phosphorylation

up-regulates activity

0.608

Phosphorylation of FcgammaRIIa/c by Lyn is clearly dependent on the presence of Y-298, since all mutants lacking this residue are not phosphorylated by this PTK. This result suggests that Y-298 might be the only tyrosine residue of FcgammaRIIa/c phos- phorylated by Lyn.

SIGNOR-249379

O14544

P10721

1

ubiquitination

down-regulates

0.678

Suppressor of cytokine signaling 6 (socs6) is a member of the socs family of e3 ubiquitin ligases that can interact with c-kit and suppress c-kit-dependent pathways. / we demonstrate that socs6 has ubiquitin ligase activity toward c-kit and regulates c-kit protein turnover in cells

SIGNOR-169145

Q15154

Q86YT6

0

ubiquitination

down-regulates

0.371

We demonstrate that the E3 ubiquitin ligase MIB1 is a new component of centriolar satellites, which interacts with and ubiquitylates AZI1 and PCM1 and suppresses primary cilium formation.

SIGNOR-272878

P33981

P24941

0

phosphorylation

up-regulates quantity by stabilization

0.411

Cdk2 phosphorylates Mps1 at T468, attenuating the function of a degradation signal found in amino acids 420\u2013507 (encoded by exons 12 and 13) and allowing the accumulation of a centrosomal pool of Mps1 that represents no more than 10% of total cellular Mps1 ( xref ).

SIGNOR-279398

Q9Y613

Q13976

0

phosphorylation

up-regulates

0.354

Pkgi also directly phosphorylates fhod1, and studies with wild-type and mutant fhod1-derived peptides identify ser-1131 in the fhod1 c terminus as the unique pkgi phosphorylation site in fhod1. phosphorylation of three conserved residues within the dad domain activates fhod1 while binding to rac regulates fhod1 subcellular localization

SIGNOR-123646

Q07869

P27361

0

phosphorylation

up-regulates activity

0.601

We now demonstrate that amino acids 1-92 of hPPARalpha contain an activation function (AF)-1-like domain, which is further activated by insulin through a pathway involving the mitogen-activated protein kinases p42 and p44. Further analysis of the amino-terminal region of PPARalpha revealed that the insulin-induced trans-activation occurs through the phosphorylation of two mitogen-activated protein kinase sites at positions 12 and 21, both of which are conserved across evolution.

SIGNOR-249474

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

Q00535

Q12879

1

phosphorylation

up-regulates activity

0.525

Here, we demonstrate that cyclin dependent kinase-5 (Cdk5) associates with and phosphorylates NR2A subunits at Ser-1232 in vitro and in intact cells. Moreover, we show that roscovitine, a selective Cdk5 inhibitor, blocks both long-term potentiation induction and NMDA-evoked currents in rat CA1 hippocampal neurons. These results suggest that Cdk5 plays a key role in synaptic transmission and plasticity through its up-regulation of NMDARs.

SIGNOR-250666

Q9HAU4

P37173

1

ubiquitination

down-regulates activity

0.595

Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps.

SIGNOR-195681

Q01860

Q96GD4

0

phosphorylation

down-regulates activity

0.38

Aurkb phosphorylates Oct4(S229) during G2/M phase, leading to the dissociation of Oct4 from chromatin, whereas PP1 binds Oct4 and dephosphorylates Oct4(S229) during M/G1 transition, which resets Oct4-driven transcription for pluripotency and the cell cycle.

SIGNOR-279592

Q8NG66

O14757

0

phosphorylation

up-regulates

0.264

We demonstrate that chk1 (checkpoint kinase 1) directly activates nek11 by phosphorylating it on ser 273

SIGNOR-187863

Q9UKV5

Q14258

0

polyubiquitination

down-regulates quantity by destabilization

0.364

We further demonstrate that TRIM25 ubiquitylates gp78 and that overexpression of TRIM25 accelerates the degradation of gp78. Our data suggest that TRIM25 not only cooperates with gp78 in polyubiquitylation of AMF but also gauges the steady-state level of gp78.

SIGNOR-272176

P45983

O14733

0

phosphorylation

up-regulates

0.699

Jnk is activated by jnk-activating kinase 1 (jnkk1), a dual specificity protein kinase that phosphorylates jnk on threonine 183 and tyrosine 185 residues.

SIGNOR-51199

P68400

P05455

1

phosphorylation

up-regulates

0.337

Prior studies indicate that hla is activated by phosphorylation of serine-366 by protein kinase ck2, neutralizing a negative effect of a short basic motif (sbm)

SIGNOR-160761

P09758

Q05655

0

phosphorylation

down-regulates activity

0.2

Analyses using HCT116 cells expressing WT Trop-2 (HCT116/WT) or Trop-2 alanine-substituted at Ser-303 (HCT116/S303A) or Ser-322 (HCT116/S322A) revealed that Trop-2 is phosphorylated at Ser-322. sing protein kinase C (PKC) inhibitors and PKC-specific siRNAs, we found that PKCα and PKCδ are responsible for Trop-2 phosphorylation.

SIGNOR-273820

Q08881

P51813

1

phosphorylation

up-regulates activity

0.334

Itk phosphorylated Bmx-SH3 to a low extent. pY positions correspond to the residues Y215 and Y223 in Bmx. Tec family protein tyrosine kinases (TFKs) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop.

SIGNOR-251331

Q8N6T7

P01375

1

deacetylation

up-regulates

0.314

Sirt6 regulates tnf-alfa secretion through hydrolysis of long-chain fatty acyl lysine

SIGNOR-201662

Q99683

O14548

1

phosphorylation

up-regulates activity

0.2

Phosphorylation of EB1 by ASK1 promotes the binding of EB1 to CLIP-170 and p150 glued.

SIGNOR-278341

Q04771

Q15797

1

phosphorylation

up-regulates activity

0.703

ALK2 receptor specifically interacts with and phosphorylates Smad1 protein. ALK2 Activates Smad1 and Induces BMP-specific Signals. Biochemical analysis revealed that constitutively active ALK2 associated with and phosphorylated Smad1 on the COOH-terminal SSXS motif

SIGNOR-251439

Q13541

P49674

0

phosphorylation

down-regulates

0.2

Mechanistic investigations showed that ck1_ interacted with and phosphorylated 4e-bp1 at two novel sites t41 and t50, which were essential for 4e-bp1 inactivation along with increased mrna translation and cell proliferation.

SIGNOR-203240

P49841

P41236

1

phosphorylation

up-regulates activity

0.412

Protein phosphatase 1 (PP1) is complexed with inhibitor 2 (I-2) in the cytosol. In rabbit muscle extract PP1.I-2 is activated upon preincubation with ATP/Mg. This activation is caused by phosphorylation of I-2 on Thr(72) by glycogen synthase kinase 3 (GSK3).

SIGNOR-251257

P84243

Q15418

0

phosphorylation

down-regulates activity

0.2

Phosphorylation at ser-11 (h3s10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or uv irradiation and result in the activation of genes, such as c-fos and c-jun.

SIGNOR-70428

P17655

P49841

1

cleavage

up-regulates activity

0.285

Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase

SIGNOR-251613

P01215

P50458

0

transcriptional regulation

up-regulates quantity by expression

0.266

In Cos cells, LH-2 activated the a-subunit promoter approximately twofold

SIGNOR-266055

Q02156

P28329

1

phosphorylation

up-regulates

0.312

We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation

SIGNOR-129312

Q9NRA0

Q96PU5

0

ubiquitination

down-regulates quantity by destabilization

0.2

In this study, we found that NEDD4L interacted with SphK2 to ubiquitinate SphK2 protein.|NEDD4L Mediates the Degradation of SphK2 Protein Through the Ubiquitin-Proteasomal Pathway.

SIGNOR-278660

Q13627

Q8IXJ6

1

phosphorylation

up-regulates activity

0.293

This Minibrain/Dyrk1a kinase phosphorylates and activates the Silent information regulator 2/Sirtuin1 deacetylase, which in turn deacetylates and activates the FOXO transcription factor.

SIGNOR-279990