GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q06124	Q14451	1	dephosphorylation	up-regulates activity	0.435	Dephosphorylation of Grb7 was blocked by the SHP inhibitor NSC-87877 (Zhan et al., 2009), supporting the specificity of SHP-2 in dephosphorylating Grb7.\|Nuclear SHP-2 mediates the formation of an EGF induced complex of Grb7, HuR, and CRM1.\|Using the \u03ba\u2013opioid receptor (OR [KOR]) as a model, we demonstrate that EGF activates nuclear SHP-2 (Src homology region 2\u2013containing tyrosine phosphatase), which dephosphorylates Grb7 in the nucleus.	SIGNOR-277169
Q9NR81	P61586	1	guanine nucleotide exchange factor	up-regulates activity	0.777	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-260530
O43318	P62820	1	phosphorylation	up-regulates activity	0.2	TAK1 preferentially phosphorylates the inactive (GDP-bound) state of Rab1. Phosphorylation of Rab1 disrupts interaction with GDP dissociation inhibitor 1 (GDI1), but not guanine exchange factor (GEF) or GTPase-activating protein (GAP) enzymes, and is exclusive to membrane-localized Rab1, suggesting phosphorylation may stimulate Rab1 membrane association. Furthermore, we found phosphorylation of Rab1 at T75 to be essential for Rab1 function.	SIGNOR-277270
Q96GD4	Q9Y2I6	1	phosphorylation	up-regulates	0.252	Importantly, nlp is characterized as a novel substrate of aurora b and can be phosphorylated by aurora b. The specific phosphorylation sites are mapped at ser-185, ser-448, and ser-585. The phosphorylation at ser-448 and ser-585 is likely required for nlp association with aurora b and localization at midbody. Meanwhile, the phosphorylation at ser-185 is vital to nlp protein stability. Disruptions of these phosphorylation sites abolish cytokinesis and lead to chromosomal instability.	SIGNOR-168053
P38936	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.4	Glycogen synthase kinase 3beta phosphorylates p21waf1/cip1 for proteasomal degradation after uv irradiationhere, we show that ser-114 phosphorylation of p21 protein by glycogen synthase kinase 3beta (gsk-3beta) is required for its degradation in response to uv irradiation	SIGNOR-152941
P36897	Q9H0M0	0	ubiquitination	down-regulates	0.533	Similar to smurfs, wwp1 associated with smad7 and induced its nuclear export, and enhanced binding of smad7 to tgf-beta type i receptor to cause ubiquitination and degradation of the receptor. Consistent with these results, wwp1 inhibited phosphorylation of smad2 induced by tgf-beta. Wwp1 thus negatively regulates tgf-beta signaling in cooperation with smad7	SIGNOR-126581
P16403	P78527	0	phosphorylation	down-regulates activity	0.2	Similarly, DNA-PK-mediated phosphorylation of H1.2 at T146 enhances p53 transcriptional activity by impeding H1.2 binding to p53 and thereby attenuating its suppressive effects on p53 transactivation.	SIGNOR-273834
P04637	Q96GD4	0	phosphorylation	down-regulates	0.719	We show that aurora b phosphorylates p53 at s183, t211, and s215 to accelerate the degradation of p53 through the polyubiquitination-proteasome pathway, thus functionally suppressing the expression of p53 target genes involved in cell cycle inhibition and apoptosis (e.g., p21 and puma).	SIGNOR-197598
P68400	Q9ULV4	1	phosphorylation	up-regulates	0.2	We demonstrate that crn2 is a binding partner and substrate of protein kinase ck2, which phosphorylates crn2 at s463 in its c-terminal coiled coil domain	SIGNOR-196193
P54274	P68400	0	phosphorylation	up-regulates	0.2	Regulation of telomeric repeat binding factor 1 binding to telomeres by casein kinase 2-mediated phosphorylation. Mapping of the ck2 target site identified threonine 122 as a substrate in trf1. A threonine to alanine change at this position led to a diminished dna binding due to reduced dimerization of trf1.	SIGNOR-178034
Q9UQQ2	P43403	0	phosphorylation	up-regulates	0.363	In vitro tyrosine phosphorylation of lnk by lck and zap-70. Tyrosine 297 would appear to be an attractive target for phosphorylation within the c-terminal domain. Our studies suggest that although lnk may participate in tcr signaling, its functions are in no way limiting during t cell development or activation.	SIGNOR-48854
P49840	P05412	1	phosphorylation	down-regulates	0.331	Phosphorylation of recombinant human c-jun proteins in vitro by gsk-3 decreases their dna-binding activity.	SIGNOR-21780
Q9H2X6	Q06413	1	phosphorylation	down-regulates activity	0.399	HIPK2 associates with the MEF2C\u2013HDAC4 complex and phosphorylates MEF2C.	SIGNOR-279192
P53671	Q13464	0	phosphorylation	up-regulates	0.632	Specific activation of lim kinase 2 via phosphorylation of threonine 505 by rock, a rho-dependent protein kinase	SIGNOR-82755
O00308	Q07912	0	phosphorylation	up-regulates activity	0.342	ACK1 phosphorylates WWP2 at the 2, 3-linker and partially activates the ubiquitination ligase activity.\|Activation of E3 ubiquitin ligase WWP2 by non-receptor tyrosine kinase ACK1.	SIGNOR-279302
Q9Y2K7	Q16665	0	transcriptional regulation	up-regulates quantity by expression	0.2	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271566
P16220	P48729	0	phosphorylation	up-regulates	0.312	Ser108, ser111 and ser114, located in a region matching the consensus sequence for the casein kinase ii target, were required.These results strongly suggest that the casein kinase ii target region is involved in cell cycle-regulated phosphorylation of the creb protein and also in transcriptional enhancement.	SIGNOR-64258
P03217	Q9NR96	1	post transcriptional regulation	down-regulates quantity by destabilization	0.2	The EBV lytic-phase protein BGLF5 reduces TLR9 expression through mRNA degradation. We established that the EBV early protein BGLF5 degrades TLR9 mRNA in vitro, providing a mechanism for its contribution to TLR9 downregulation.	SIGNOR-266633
Q9GZT9	Q16665	1	hydroxylation	down-regulates quantity by destabilization	0.918	Hypoxia-inducible factor-1 (HIF-1) is a key regulator of erythropoiesis. In this article, we report 3 novel mutations, P378S, A385T, and G206C, on the EGLN1 gene encoding the negative HIF-1α regulator prolyl hydroxylase domain-2 (PHD2) in 3 patients with isolated erythrocytosis. These mutations impair PHD2 protein stability and partially reduce PHD2 activity, leading to increased HIF-1α protein levels in cultured cells.\|Oxygen-dependent hydroxylation by the prolyl hydroxylase domain-2 (PHD2) protein marks HIF-1alpha for ubiquitination by the von Hippel Lindau (VHL) tumor suppressor protein, leading to proteasomal degradation	SIGNOR-261994
P46531	O60684	0	relocalization	up-regulates	0.2	Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7. importins alpha3, alpha4 (and to a lesser extent, alpha7) mediate nuclear import of nicd and thus are directly involved in notch signaling.	SIGNOR-165343
Q9Y6E0	P61006	1	phosphorylation	up-regulates activity	0.275	In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. \|Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.\|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease	SIGNOR-260265
P12931	Q15691	1	phosphorylation	down-regulates activity	0.2	These data suggest that Src phosphorylates endogenous EB1 at Y247.	SIGNOR-278215
P00441	P14174	0	relocalization	down-regulates quantity by destabilization	0.307	Here, we show that MIF inhibits mutant SOD1 nuclear clearance when overexpressed in motor neuron-like NSC-34 cells\|SOD1WT is evenly distributed between the cytoplasm and the nucleus while mutant SOD1G93A shows predominantly cytoplasmic distribution (Fig. 1a, b). Expression of MIF in cells expressing SOD1WT had no effect on the distribution of the SOD1WT–EGFP protein. However, expression of MIF together with the mutant SOD1G93A–EGFP, inhibited the nuclear clearance of misfolded SOD1 resulting in a more wild-type-like distribution of the mutant SOD1 protein	SIGNOR-262797
Q16678	P35869	0	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
P49768	P49841	0	phosphorylation	down-regulates activity	0.586	We demonstrate that phosphorylation of serines 353 and 357 by glycogen synthase kinase-3beta (gsk3beta) induces a structural change of the hydrophilic loop of ps1the structural change of ps1 reduces the interaction with beta-catenin leading to decreased phosphorylation and ubiquitination of beta-catenin.	SIGNOR-153627
P07550	Q05655	0	phosphorylation	down-regulates activity	0.352	We investigate the role of the beta 2-adrenergic receptor phosphorylation by protein kinase C in this regulatory process. Mutation of the serine-261, -262, -344 and -345 of the beta 2-adrenergic receptor prevented the phorbol-ester-induced phosphorylation of the receptor. This mutation also abolished the phorbol-ester-induced decrease in high-affinity agonist binding and potency of the beta 2-adrenergic receptor. We suggest that protein kinase C mediated phosphorylation of the receptor promotes its functional uncoupling.	SIGNOR-248855
P04035	Q9UKV5	0	ubiquitination	down-regulates quantity by destabilization	0.492	Gp78 mediates the sterol regulated ubiquitination of HMGCR.	SIGNOR-278622
Q16513	O15553	1	phosphorylation	down-regulates activity	0.349	PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome.	SIGNOR-275464
P20807	P49841	1	cleavage	up-regulates activity	0.272	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-251607
P27361	P48431	1	phosphorylation	down-regulates activity	0.452	Mass spectrum analysis was employed after an in vitro kinase assay in which cells were incubated with or without ERK1-active kinase, and the results demonstrated that Sox2 was phosphorylated by ERK1 directly at S251, which was further verified by western blotting for the specific antibody targeting S251 phosphorylated Sox2 after the in vitro kinase assay.\|Mechanistically, ERK1 kinase promoted autophagic degradation of Sox2 via phosphorylation of Sox2 at Ser251 and further SUMOylation of Sox2 at Lys245 in non CSCs.	SIGNOR-279071
P51532	P48730	0	phosphorylation	down-regulates quantity by destabilization	0.2	We reveal that CK1δ phosphorylates Brg1 at Ser31/Ser35 residues to facilitate the binding of Brg1 to FBW7, leading to ubiquitination-mediated degradation.	SIGNOR-277407
P08254	P10451	1	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
Q9UL17	Q96NM4	0	transcriptional regulation	up-regulates quantity by expression	0.294	We subsequently found that TOX2 was independent of ETS-1 but could directly upregulate the transcription of TBX21 (encoding T-BET).	SIGNOR-266097
P62330	Q9Y2X7	0	guanine nucleotide exchange factor	up-regulates activity	0.714	Activated RAC1 interacts with GIT1, a GAP protein of ARF6, and causes the inactivation of ARF6 [78]. As ARF6 plays a role in the promotion of the recycling of macropinosomes to the plasma membrane, the inactivation of ARF6 by RAC1 reduces the recycling of macropinosomes.	SIGNOR-277784
O60216	P04114	1	transcriptional regulation	down-regulates quantity	0.2	The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector.	SIGNOR-259974
P19484	O75807	1	transcriptional regulation	up-regulates quantity by expression	0.2	We found that the main regulator of the starvation-induced transcriptional program, TFEB, counteracts protein synthesis inhibition by directly activating expression of GADD34, a component of the protein phosphatase 1 complex that dephosphorylates eIF2α.	SIGNOR-276789
O00124	P55072	1	relocalization	down-regulates quantity	0.521	The human protein named Rep8 or Ubxd6 as a new cofactor of p97. Rep8 tethers p97 to the ER membrane for efficient ER-associated degradation.	SIGNOR-261002
P25054	Q05655	0	phosphorylation	down-regulates activity	0.2	APC is Phosphorylated by PKCdelta in Intact RKO Cells.	SIGNOR-279650
P28482	P40763	1	phosphorylation	down-regulates activity	0.75	ERK2 phosphorylates Stat3 on three serine-containing peptides and decreases its tyrosine phosphorylation induced by EGF treatment.\|Here, we report that ERK2 activated by its upstream kinase, MEK1, represses Stat3 transcriptional activity induced by Src or Jak-2.	SIGNOR-279635
P12931	Q13813	1	phosphorylation	up-regulates	0.563	Using mutagenesis on recombinant peptides, we identified the residue y1176 located in the calpain cleavage site of alpha ii-spectrin, near the sh3 domain, as an in vitro substrate for src kinase and lmw-ptp a. phosphorylation of this residue decreases spectrin sensitivity to calpain in vitro.	SIGNOR-86718
P13762	Q8TCQ1	0	polyubiquitination	down-regulates quantity by destabilization	0.2	Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination.	SIGNOR-271409
P45985	Q9H3Y6	0	phosphorylation	down-regulates activity	0.2	SRMS directly phosphorylates MKK4 and inhibits MKK4-JNK-c-Jun activation upon platinum treatment. Platinum treatment-induced ROS activates SRMS, which inhibits MKK4 kinase activity by directly phosphorylating MKK4 at Y269 and Y307, and consequently attenuates MKK4-JNK activation.	SIGNOR-277902
Q9NPB6	P41743	0	phosphorylation	up-regulates quantity by stabilization	0.866	APKC associates and phosphorylates Par6 on S345. aPKC expression stabilizes Par6 protein levels. We show that the aPKC, PKCι, interacts with TGF-β receptors through Par6 and that these proteins localize to the leading edge of migrating cells. Furthermore, Par6 phosphorylation on serine 345 by TGF-β receptors is enhanced in the presence of aPKC. aPKC kinase activity, as well as an association with Par6, were found to be important for Par6 phosphorylation.	SIGNOR-276432
P21333	P17612	0	phosphorylation	up-regulates	0.2	Site-directed mutagenesis analysis indicated that serine 2152 is the unique substrate in the c-terminal region of abp for endogenously activated pka.	SIGNOR-126659
Q14934	P51812	0	phosphorylation	up-regulates	0.385	The results indicated that rsk2 phosphorylated two additional sites at ser289 (peptide 2) and ser344 (peptide 3)rsk2 induced nuclear localization of nfat3. Rsk2 phosphorylated nfat3 in vitro (km=3.559 microm), and activation of nfat3 by rsk2 enhanced the promoter activity of nfat3 downstream target genes in vivo.	SIGNOR-234473
Q9Y4X5	Q9NZQ7	1	polyubiquitination	down-regulates quantity by destabilization	0.2	We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation.	SIGNOR-277553
P46527	P31749	0	phosphorylation	down-regulates	0.85	Because Thr198-phosphorylated p27Kip1 was localized only in the cytoplasm, Akt might promote 14-3-3 binding to p27Kip1 by phosphorylation at Thr198, allowing its cytoplasmic localization and degradation.	SIGNOR-88294
P63000	Q8N1I0	0	guanine nucleotide exchange factor	up-regulates activity	0.586	DOCK4 (dedicator for cytokinesis 4), a guanine nucleotide exchange factor (GEF) for the small GTPase Rac1, is one of few genes that are associated with both ASD and dyslexia.	SIGNOR-266823
Q13131	Q14694	1	phosphorylation	up-regulates activity	0.309	Under energy stress, USP10 activity in turn is enhanced through AMPK-mediated phosphorylation of Ser76 of USP10.	SIGNOR-277207
O15269	P00519	0	phosphorylation	down-regulates	0.2	We demonstrated that the er-resident human protein serine palmitoyltransferase long chain-1 (sptlc1), which is the first enzyme of sphingolipid biosynthesis, is phosphorylated at tyr(164) by the tyrosine kinase abl. this occurred through the specific abl-mediated phosphorylation of sptlc1 on tyr164, leading to the attenuation of its activity.	SIGNOR-202003
P01116	Q06124	0	dephosphorylation	up-regulates activity	0.66	Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling.	SIGNOR-255982
Q7Z628	Q13153	0	phosphorylation	down-regulates activity	0.249	In this work we show that the Rac/Cdc42hs-regulated protein kinase PAK1 down-regulates the activity of the RhoA-specific guanine nucleotide exchange factor NET1. Specifically, PAK1 phosphorylates NET1 on three sites in vitro: serines 152, 153, and 538. Replacement of serines 152 and 153 with glutamate residues down-regulates the activity of NET1 as an exchange factor in vitro and its ability to stimulate actin stress fiber formation in cells. Using a phospho-specific antibody that recognizes NET1 phosphorylated on serine 152, we show that PAK1 phosphorylates NET1 on this site in cells and that Rac1 stimulates serine 152 phosphorylation in a PAK1-dependent manner.	SIGNOR-263018
P24941	Q05209	1	phosphorylation	down-regulates activity	0.382	In the present study, we found that S19 site phosphorylation of PTPN12 by CDK2 discharged its antitumor activity by down-regulation of its inhibitory role in cell migration, but not affecting its other regulatory functions.	SIGNOR-277366
Q05513	P05023	1	phosphorylation	up-regulates activity	0.2	Na,K-ATPase alpha(1) subunit was phosphorylated by PKC in hypoxia-treated AEC. In AEC treated with a PKC-zeta antagonist peptide or with the Na,K-ATPase alpha(1) subunit lacking the PKC phosphorylation site (Ser-18), hypoxia failed to decrease Na,K-ATPase abundance and function.	SIGNOR-263181
Q96AX9	Q13224	1	ubiquitination	down-regulates quantity	0.366	Mib2 is localized to the PSD of dendrites in hippocampal neurons and directly ubiquitinates GluN2B in a manner dependent on the non receptor tyrosine kinase Fyn.\|These findings suggest that Mib2 mediates proteasome dependent degradation of GluN2B subunits, which may provide a reciprocal mechanism to SCF Fbx2 regulation of GluN2A.	SIGNOR-278762
Q9UQ88	Q13153	1	phosphorylation	up-regulates activity	0.384	CDK11p58 phosphorylation of PAK1 Ser174 promotes DLC2 binding and roles on cell cycle progression\|We show that PAK1 is a substrate of CDK11p58 and can be strongly activated upon phosphorylation.	SIGNOR-273026
P51955	Q12834	1	phosphorylation	up-regulates activity	0.945	In summary, we have demonstrated that Nek2 can associate with and phosphorylate Mad2 and Cdc20.\|The results presented here support a model in which Nek2 modulates the functions of Mad2 and Cdc20 in the mitotic checkpoint and elevation of Nek2 levels may contribute to chromosome instability by interfering with the control of the checkpoint.	SIGNOR-278366
P05771	P41180	1	phosphorylation	down-regulates activity	0.319	Expression of a mutant CaR in which the major PKC phosphorylation site is altered by substitution of alanine for threonine (T888A) eliminated oscillatory behavior, producing [Ca(2+)](i) responses almost identical to those produced by the wild type CaR exposed to PKC inhibitors. These results support a model in which phosphorylation of the CaR at the inhibitory threonine 888 by PKC provides the negative feedback needed to cause [Ca(2+)](i) oscillations mediated by this receptor.	SIGNOR-249176
P07203	P42684	0	phosphorylation	up-regulates activity	0.322	GPx1 also functions as a substrate for c-Abl- and Arg-mediated phosphorylation on Tyr-96. The results further show that c-Abl and Arg stimulate GPx activity and that these kinases contribute to GPx-mediated protection of cells against oxidative stress.	SIGNOR-104328
P35222	P31749	0	phosphorylation	up-regulates	0.805	Phosphorylation of beta-catenin by akt promotes beta-catenin transcriptional activity\|we have demonstrated that akt phosphorylates beta-catenin at ser552 in vitro and in vivo.	SIGNOR-252499
P01106	P62633	0	transcriptional regulation	down-regulates quantity by repression	0.303	These data verified that the binding of CNBP with c-myc promoter G-quadruplex can indeed down-regulate its associated gene expression for a certain period of time. This result with human CNBP is somehow consistent with previous reports that c-myc G-quadruplex serves as a silencer of c-myc transcription [7] and CNBP promotes the formation of c-myc G-quadruplex.	SIGNOR-261571
P25963	P51812	0	phosphorylation	down-regulates quantity by destabilization	0.368	Here, we show that RSK2 is activated by treatment with tumor necrosis factor-alpha (TNF-alpha) and directly phosphorylates IkappaBalpha at Ser 32, leading to IkappaBalpha degradation.	SIGNOR-279108
Q92831	P68431	1	acetylation	down-regulates activity	0.2	The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.	SIGNOR-269611
P11912	P07948	0	phosphorylation	up-regulates activity	0.738	Y182 of CD79a appears to be the initial and preferred site of Ag receptor phosphorylation by Src family kinases. In vitro, Src family Lyn and Fyn predominantly phosphorylate this residue in CD79a, and Y195 does so in CD79b. phosphorylation of Y182 alone can lead to further kinase activation and/or effector focusing necessary for phosphorylation of certain downstream targets, such as p62, p110, and Shc, but not others, such as Vav.	SIGNOR-251397
P52292	Q13131	0	phosphorylation	up-regulates	0.2	Ampk phosphorylated importin alpha1 on ser(105). Accordingly, expression of importin alpha1 proteins bearing k22r or s105a mutations failed to mediate the nuclear import of hur in intact cells. Our results point to importin alpha1 as a critical downstream target of ampk and key mediator of ampk-triggered hur nuclear import.	SIGNOR-128629
O15169	P36873	0	dephosphorylation	down-regulates activity	0.269	The data suggest that PP1 controls Wnt signaling through interaction with, and regulated dephosphorylation of, axin\| Axin phosphorylation markedly enhances the binding of glycogen synthase kinase 3, leading to a more active beta-catenin destruction complex. Wnt-regulated changes in axin phosphorylation, mediated by PP1, may therefore determine beta-catenin transcriptional activity\| Four sites, S80, S82, S222, and S473, were identified to be PP1 regulated	SIGNOR-248494
Q8WXG1	Q05516	0	transcriptional regulation	up-regulates quantity by expression	0.2	Promoter regions from the PLZF-regulated transcripts Rsad2 and Ifit2 were fused to luciferase and activity was measured after IFN treatment. Overexpression of PLZF in RCC1 or ACHN cells produced a dose-dependent induction of the reporter promoters.	SIGNOR-261023
Q8NFU7	P31269	1	transcriptional regulation	up-regulates quantity by expression	0.306	Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9.	SIGNOR-259094
Q9BY66	Q16695	1	demethylation	up-regulates activity	0.2	KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.	SIGNOR-264309
P53350	Q13153	0	phosphorylation	up-regulates	0.552	We show here that pak1 is required for cell proliferation, mitotic progression and plk1 activity in hela cells. phosphorylation of plk1 on ser 49 is important for metaphase-associated events.	SIGNOR-178353
O14965	P23528	1	phosphorylation	down-regulates activity	0.316	However, this study identified that CFL-1 also acts as a direct substrate of Aur-A, which phosphorylates CFL-1 at multiple sites, including S3, S8, and T25, resulting in its inactivation.\|In early cell mitotic phases, LIMK1 and Aur-A phosphorylate and inactivate CFL-1, while at the later stages, SSH-1 inactivates LIMK1 and dephosphorylates and activates CFL-1 [33] .	SIGNOR-279798
P28069	Q969G2	0	transcriptional regulation	up-regulates quantity by expression	0.514	We show that normal LHX4 binds to a human-specific element and subsequently activates transcription from the proximal upstream regulatory sequence of POUIF1, a gene encoding a POU homeodomain transcription factor known as the main regulator of GH expression.	SIGNOR-266056
P53041	Q99683	1	dephosphorylation	down-regulates activity	0.597	After exposure of cells to H2O2, ASK1 is transiently activated by autophosphorylation at Thr845. The protein then associates with PP5 (protein serine/threonine phosphatase 5), which inactivates ASK1 by dephosphorylation of Thr845.	SIGNOR-248540
P46937	P49336	0	phosphorylation	up-regulates activity	0.321	CDK8 phosphorylates YAP and promotes its activation. Of interest, mutating four amino acid positions (T119, S128, S289, and S367) to alanines (YAP-4A) completely blocked phosphorylation (Fig. 6J), suggesting that CDK8 phosphorylates these sites in YAP in vitro.	SIGNOR-277651
P53350	Q9P2P6	1	phosphorylation	down-regulates quantity by destabilization	0.309	NI indicates the noninduced control. (B) Plk1 phosphorylates STARD9-motor domain at serine 312.	SIGNOR-279806
Q96SR6	Q8NFU7	0	transcriptional regulation	up-regulates quantity by expression	0.2	Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9.	SIGNOR-259095
Q00987	Q8NEZ5	0	ubiquitination	down-regulates quantity by destabilization	0.2	SCFFBXO22 targets HDM2 for degradation and modulates breast cancer cell invasion and metastasis\|we discovered Skp1-Cullin 1-FBXO22-ROC1 (SCFFBXO22) as the most dominating HDM2 E3 ubiquitin ligase from human proteome. The results of protein decay rate analysis, ubiquitination, siRNA-mediated silencing, and coimmunoprecipitation experiments support a hypothesis that FBXO22 targets cellular HDM2 for ubiquitin-dependent degradation.	SIGNOR-273440
P35398	Q8IVA1	1	transcriptional regulation	up-regulates quantity by expression	0.2	RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.	SIGNOR-266849
O94916	Q8N752	0	phosphorylation	up-regulates activity	0.2	However, the siRNA knockdown of CK1α1L significantly reduced the nuclear export of OREBP/TonEBP under hypotonic conditions (Fig. 5F). Taken together, these data suggest that CK1α1L is the kinase that phosphorylates Ser-158 in the regulation of OREBP/TonEBP export.	SIGNOR-274111
P05198	Q86TM6	0	ubiquitination	down-regulates quantity by destabilization	0.2	HRD1 overexpression also decreased the expression of eIF2alpha and p-eIF2alpha in HKC-8 cells.\|HRD1 promoted eIF2alpha ubiquitylation and degradation, thereby providing a protective mechanism that suppressed tubular epithelial cell apoptosis.	SIGNOR-278671
P04637	P02511	1	transcriptional regulation	up-regulates quantity by expression	0.47	Aberrant expression of CRYAB has been shown to be associated with several neurological diseases and malignant neoplasms. To identify transcriptional regulators of CRYAB expression, we examined its promoter for binding sites of transcription factors and identified four potential AP-2 binding sites in addition to a p53 binding site reported previously\|Taken together, our results indicate that AP-2_ up-regulates the transcription of the CRYAB gene through stabilizing p53	SIGNOR-253638
P04049	Q13118	1	phosphorylation	down-regulates quantity by destabilization	0.2	RAF1 phosphorylates the Thr93 site of KLF10 in vivo. Since the phosphorylation of Thr93 enables KLF10 and PIN1 to bind, it seems likely that RAF-1 will have an effect on KLF10 stability that is similar to that of PIN1.PIN1 facilitates KLF10 protein degradation. (	SIGNOR-276502
Q99626	Q12864	1	transcriptional regulation	up-regulates quantity by expression	0.406	The present study aims to identify the transcription factors which interact and regulate CDH17 promoter activity that might contribute to the up-regulation of CDH17 gene in human HCC\|we identified hepatic nuclear factor 1α (HNF1α) and caudal-related homeobox 2 (CDX2) binding sites at the proximal promoter region which modulate the CDH17 promoter activities in two HCC cell lines (Hep3B and MHCC97L)	SIGNOR-253963
P78527	P07954	1	phosphorylation	up-regulates activity	0.2	We show that exposure to ionizing radiation induces DNA-PK-dependent phosphorylation of nuclear fumarase at Thr 236, which leads to an interaction between fumarase and the histone variant H2A.Z at DNA double-strand break (DSB) regions.	SIGNOR-266349
Q13586	Q13153	0	phosphorylation	up-regulates activity	0.354	Taken together, our data demonstrate that PAK1 interacts with STIM1 and phosphorylates specific STIM1 cytosolic domains.	SIGNOR-279244
P45983	O95644	1	phosphorylation	down-regulates activity	0.621	It has been previously shown that NF-ATc1 accumulates in the nucleus of activated CD4 + T cells from Jnk1 \n \u2212/\u2212 mice 35\u2022 and that JNK1 phosphorylates and inactivates NFATc1 in Jurkat T cells 47 , indicating that JNK1 is an inhibitor of NFAT.	SIGNOR-280031
P54296	P17612	0	phosphorylation	down-regulates	0.2	This binding is regulated in vitro by phosphorylation of a single serine residue (ser76) in the immediately adjacent amino-terminal domain mp1. M-protein phosphorylation by camp-dependent kinase a inhibits binding to myosin lmm.	SIGNOR-56395
P35637	Q9UQ80	1	sumoylation	up-regulates activity	0.336	Here, we show that Ebp1 p42 isoform can be sumoylated on both K93 and K298 residues, which mediate its nuclear translocation and are required for its anti-proliferative activity .. Hence, TLS-mediated sumoylation is required for Ebp1 transcriptional repressive activity.	SIGNOR-236904
P08151	P23443	0	phosphorylation	up-regulates	0.523	In this study, we found that an activated mtor/s6k1 pathway promotes gli1 transcriptional activity and oncogenic function through s6k1-mediated gli1 phosphorylation at ser84, which releases gli1 from its endogenous inhibitor, sufu.	SIGNOR-196756
P01909	Q86YJ5	0	ubiquitination	down-regulates quantity by destabilization	0.2	MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.	SIGNOR-271538
P45983	P38936	1	phosphorylation	up-regulates quantity by stabilization	0.672	The stress-activated protein kinases p38 alpha and jnk1 stabilize p21(cip1) by phosphorylation.\|p38 alpha and JNK1 phosphorylated p21 in vivo, and both p38 alpha and JNK1 phosphorylated p21 at Ser(130) in vitro.	SIGNOR-89440
Q13882	P18031	0	dephosphorylation	down-regulates activity	0.575	Using a variety of PTEN mutant constructs, we show that protein phosphatase activity of PTEN targets PTK6, with efficiency similar to PTP1B, a phosphatase that directly dephosphorylates PTK6 Y342.	SIGNOR-277082
P62805	O14929	0	acetylation	down-regulates activity	0.2	Histone acetyltransferase 1 is the founding member of the histone acetyltransferase superfamily and catalyzes lysine acetylation of newly synthesized histone H4\|Lys12 for direct attack of the acetyl group of the cofactor.\| It is postulated that histone acetylation, through charge neutralization of the cationic histone tails, weakens nucleosomal electrostatic interactions with anionic DNA, thus destabilizing internucleosomal contacts and nucleosomal structure and facilitating access to the promoter region for RNA polymerase and transcription factors.	SIGNOR-264790
P40763	P43405	0	phosphorylation	up-regulates activity	0.552	The current study indicates that the plasma cell malignancy is also associated with Syk-activated STAT3 directly downstream of reelin-induced integrin \u03b21 engagement and FAK/Src activation (Figure xref ).\|The integrin-activated spleen tyrosine kinase (Syk) was shown to promote STAT3 phosphorylation [42, 44].	SIGNOR-279298
P02452	Q8IYK4	0	glycosylation	up-regulates activity	0.442	Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.	SIGNOR-261156
O75385	P19367	1	phosphorylation	up-regulates activity	0.257	Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).	SIGNOR-274033
Q13627	O94826	1	phosphorylation	up-regulates activity	0.2	Phosphorylation of TOM70 Ser91 by DYRK1A stimulates interaction of TOM70 with the core TOM translocase.	SIGNOR-279994
P78559	Q13627	0	phosphorylation	up-regulates activity	0.2	The phosphorylation of MAP1A and MAP2 by Dyrk1A was further confirmed by immunoprecipitating these proteins from the soluble fraction obtained after phosphorylating MTs (XREF_FIG).	SIGNOR-279032
P29353	P35968	0	relocalization	up-regulates activity	0.711	In a similar fashion, KDR associates with Grb2 and Nck in a ligand-dependent fashion, suggesting Shc, Grb2, and Nck as potential candidates involved in the regulation of endothelial function.	SIGNOR-261949
Q9NY46	Q96PU5	0	ubiquitination	down-regulates quantity by destabilization	0.283	The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).	SIGNOR-253464

Q06124

Q14451

1

dephosphorylation

up-regulates activity

0.435

Dephosphorylation of Grb7 was blocked by the SHP inhibitor NSC-87877 (Zhan et al., 2009), supporting the specificity of SHP-2 in dephosphorylating Grb7.|Nuclear SHP-2 mediates the formation of an EGF induced complex of Grb7, HuR, and CRM1.|Using the \u03ba\u2013opioid receptor (OR [KOR]) as a model, we demonstrate that EGF activates nuclear SHP-2 (Src homology region 2\u2013containing tyrosine phosphatase), which dephosphorylates Grb7 in the nucleus.

SIGNOR-277169

Q9NR81

P61586

1

guanine nucleotide exchange factor

up-regulates activity

0.777

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-260530

O43318

P62820

1

phosphorylation

up-regulates activity

0.2

TAK1 preferentially phosphorylates the inactive (GDP-bound) state of Rab1. Phosphorylation of Rab1 disrupts interaction with GDP dissociation inhibitor 1 (GDI1), but not guanine exchange factor (GEF) or GTPase-activating protein (GAP) enzymes, and is exclusive to membrane-localized Rab1, suggesting phosphorylation may stimulate Rab1 membrane association. Furthermore, we found phosphorylation of Rab1 at T75 to be essential for Rab1 function.

SIGNOR-277270

Q96GD4

Q9Y2I6

1

phosphorylation

up-regulates

0.252

Importantly, nlp is characterized as a novel substrate of aurora b and can be phosphorylated by aurora b. The specific phosphorylation sites are mapped at ser-185, ser-448, and ser-585. The phosphorylation at ser-448 and ser-585 is likely required for nlp association with aurora b and localization at midbody. Meanwhile, the phosphorylation at ser-185 is vital to nlp protein stability. Disruptions of these phosphorylation sites abolish cytokinesis and lead to chromosomal instability.

SIGNOR-168053

P38936

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.4

Glycogen synthase kinase 3beta phosphorylates p21waf1/cip1 for proteasomal degradation after uv irradiationhere, we show that ser-114 phosphorylation of p21 protein by glycogen synthase kinase 3beta (gsk-3beta) is required for its degradation in response to uv irradiation

SIGNOR-152941

P36897

Q9H0M0

0

ubiquitination

down-regulates

0.533

Similar to smurfs, wwp1 associated with smad7 and induced its nuclear export, and enhanced binding of smad7 to tgf-beta type i receptor to cause ubiquitination and degradation of the receptor. Consistent with these results, wwp1 inhibited phosphorylation of smad2 induced by tgf-beta. Wwp1 thus negatively regulates tgf-beta signaling in cooperation with smad7

SIGNOR-126581

P16403

P78527

0

phosphorylation

down-regulates activity

0.2

Similarly, DNA-PK-mediated phosphorylation of H1.2 at T146 enhances p53 transcriptional activity by impeding H1.2 binding to p53 and thereby attenuating its suppressive effects on p53 transactivation.

SIGNOR-273834

P04637

Q96GD4

0

phosphorylation

down-regulates

0.719

We show that aurora b phosphorylates p53 at s183, t211, and s215 to accelerate the degradation of p53 through the polyubiquitination-proteasome pathway, thus functionally suppressing the expression of p53 target genes involved in cell cycle inhibition and apoptosis (e.g., p21 and puma).

SIGNOR-197598

P68400

Q9ULV4

1

phosphorylation

up-regulates

0.2

We demonstrate that crn2 is a binding partner and substrate of protein kinase ck2, which phosphorylates crn2 at s463 in its c-terminal coiled coil domain

SIGNOR-196193

P54274

P68400

0

phosphorylation

up-regulates

0.2

Regulation of telomeric repeat binding factor 1 binding to telomeres by casein kinase 2-mediated phosphorylation. Mapping of the ck2 target site identified threonine 122 as a substrate in trf1. A threonine to alanine change at this position led to a diminished dna binding due to reduced dimerization of trf1.

SIGNOR-178034

Q9UQQ2

P43403

0

phosphorylation

up-regulates

0.363

In vitro tyrosine phosphorylation of lnk by lck and zap-70. Tyrosine 297 would appear to be an attractive target for phosphorylation within the c-terminal domain. Our studies suggest that although lnk may participate in tcr signaling, its functions are in no way limiting during t cell development or activation.

SIGNOR-48854

P49840

P05412

1

phosphorylation

down-regulates

0.331

Phosphorylation of recombinant human c-jun proteins in vitro by gsk-3 decreases their dna-binding activity.

SIGNOR-21780

Q9H2X6

Q06413

1

phosphorylation

down-regulates activity

0.399

HIPK2 associates with the MEF2C\u2013HDAC4 complex and phosphorylates MEF2C.

SIGNOR-279192

P53671

Q13464

0

phosphorylation

up-regulates

0.632

Specific activation of lim kinase 2 via phosphorylation of threonine 505 by rock, a rho-dependent protein kinase

SIGNOR-82755

O00308

Q07912

0

phosphorylation

up-regulates activity

0.342

ACK1 phosphorylates WWP2 at the 2, 3-linker and partially activates the ubiquitination ligase activity.|Activation of E3 ubiquitin ligase WWP2 by non-receptor tyrosine kinase ACK1.

SIGNOR-279302

Q9Y2K7

Q16665

0

transcriptional regulation

up-regulates quantity by expression

0.2

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271566

P16220

P48729

0

phosphorylation

up-regulates

0.312

Ser108, ser111 and ser114, located in a region matching the consensus sequence for the casein kinase ii target, were required.These results strongly suggest that the casein kinase ii target region is involved in cell cycle-regulated phosphorylation of the creb protein and also in transcriptional enhancement.

SIGNOR-64258

P03217

Q9NR96

1

post transcriptional regulation

down-regulates quantity by destabilization

0.2

The EBV lytic-phase protein BGLF5 reduces TLR9 expression through mRNA degradation. We established that the EBV early protein BGLF5 degrades TLR9 mRNA in vitro, providing a mechanism for its contribution to TLR9 downregulation.

SIGNOR-266633

Q9GZT9

Q16665

1

hydroxylation

down-regulates quantity by destabilization

0.918

Hypoxia-inducible factor-1 (HIF-1) is a key regulator of erythropoiesis. In this article, we report 3 novel mutations, P378S, A385T, and G206C, on the EGLN1 gene encoding the negative HIF-1α regulator prolyl hydroxylase domain-2 (PHD2) in 3 patients with isolated erythrocytosis. These mutations impair PHD2 protein stability and partially reduce PHD2 activity, leading to increased HIF-1α protein levels in cultured cells.|Oxygen-dependent hydroxylation by the prolyl hydroxylase domain-2 (PHD2) protein marks HIF-1alpha for ubiquitination by the von Hippel Lindau (VHL) tumor suppressor protein, leading to proteasomal degradation

SIGNOR-261994

P46531

O60684

0

relocalization

up-regulates

0.2

Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7. importins alpha3, alpha4 (and to a lesser extent, alpha7) mediate nuclear import of nicd and thus are directly involved in notch signaling.

SIGNOR-165343

Q9Y6E0

P61006

1

phosphorylation

up-regulates activity

0.275

In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. |Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease

SIGNOR-260265

P12931

Q15691

1

phosphorylation

down-regulates activity

0.2

These data suggest that Src phosphorylates endogenous EB1 at Y247.

SIGNOR-278215

P00441

P14174

0

relocalization

down-regulates quantity by destabilization

0.307

Here, we show that MIF inhibits mutant SOD1 nuclear clearance when overexpressed in motor neuron-like NSC-34 cells|SOD1WT is evenly distributed between the cytoplasm and the nucleus while mutant SOD1G93A shows predominantly cytoplasmic distribution (Fig. 1a, b). Expression of MIF in cells expressing SOD1WT had no effect on the distribution of the SOD1WT–EGFP protein. However, expression of MIF together with the mutant SOD1G93A–EGFP, inhibited the nuclear clearance of misfolded SOD1 resulting in a more wild-type-like distribution of the mutant SOD1 protein

SIGNOR-262797

Q16678

P35869

0

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

P49768

P49841

0

phosphorylation

down-regulates activity

0.586

We demonstrate that phosphorylation of serines 353 and 357 by glycogen synthase kinase-3beta (gsk3beta) induces a structural change of the hydrophilic loop of ps1the structural change of ps1 reduces the interaction with beta-catenin leading to decreased phosphorylation and ubiquitination of beta-catenin.

SIGNOR-153627

P07550

Q05655

0

phosphorylation

down-regulates activity

0.352

We investigate the role of the beta 2-adrenergic receptor phosphorylation by protein kinase C in this regulatory process. Mutation of the serine-261, -262, -344 and -345 of the beta 2-adrenergic receptor prevented the phorbol-ester-induced phosphorylation of the receptor. This mutation also abolished the phorbol-ester-induced decrease in high-affinity agonist binding and potency of the beta 2-adrenergic receptor. We suggest that protein kinase C mediated phosphorylation of the receptor promotes its functional uncoupling.

SIGNOR-248855

P04035

Q9UKV5

0

ubiquitination

down-regulates quantity by destabilization

0.492

Gp78 mediates the sterol regulated ubiquitination of HMGCR.

SIGNOR-278622

Q16513

O15553

1

phosphorylation

down-regulates activity

0.349

PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome.

SIGNOR-275464

P20807

P49841

1

cleavage

up-regulates activity

0.272

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-251607

P27361

P48431

1

phosphorylation

down-regulates activity

0.452

Mass spectrum analysis was employed after an in vitro kinase assay in which cells were incubated with or without ERK1-active kinase, and the results demonstrated that Sox2 was phosphorylated by ERK1 directly at S251, which was further verified by western blotting for the specific antibody targeting S251 phosphorylated Sox2 after the in vitro kinase assay.|Mechanistically, ERK1 kinase promoted autophagic degradation of Sox2 via phosphorylation of Sox2 at Ser251 and further SUMOylation of Sox2 at Lys245 in non CSCs.

SIGNOR-279071

P51532

P48730

0

phosphorylation

down-regulates quantity by destabilization

0.2

We reveal that CK1δ phosphorylates Brg1 at Ser31/Ser35 residues to facilitate the binding of Brg1 to FBW7, leading to ubiquitination-mediated degradation.

SIGNOR-277407

P08254

P10451

1

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

Q9UL17

Q96NM4

0

transcriptional regulation

up-regulates quantity by expression

0.294

We subsequently found that TOX2 was independent of ETS-1 but could directly upregulate the transcription of TBX21 (encoding T-BET).

SIGNOR-266097

P62330

Q9Y2X7

0

guanine nucleotide exchange factor

up-regulates activity

0.714

Activated RAC1 interacts with GIT1, a GAP protein of ARF6, and causes the inactivation of ARF6 [78]. As ARF6 plays a role in the promotion of the recycling of macropinosomes to the plasma membrane, the inactivation of ARF6 by RAC1 reduces the recycling of macropinosomes.

SIGNOR-277784

O60216

P04114

1

transcriptional regulation

down-regulates quantity

0.2

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

SIGNOR-259974

P19484

O75807

1

transcriptional regulation

up-regulates quantity by expression

0.2

We found that the main regulator of the starvation-induced transcriptional program, TFEB, counteracts protein synthesis inhibition by directly activating expression of GADD34, a component of the protein phosphatase 1 complex that dephosphorylates eIF2α.

SIGNOR-276789

O00124

P55072

1

relocalization

down-regulates quantity

0.521

The human protein named Rep8 or Ubxd6 as a new cofactor of p97. Rep8 tethers p97 to the ER membrane for efficient ER-associated degradation.

SIGNOR-261002

P25054

Q05655

0

phosphorylation

down-regulates activity

0.2

APC is Phosphorylated by PKCdelta in Intact RKO Cells.

SIGNOR-279650

P28482

P40763

1

phosphorylation

down-regulates activity

0.75

ERK2 phosphorylates Stat3 on three serine-containing peptides and decreases its tyrosine phosphorylation induced by EGF treatment.|Here, we report that ERK2 activated by its upstream kinase, MEK1, represses Stat3 transcriptional activity induced by Src or Jak-2.

SIGNOR-279635

P12931

Q13813

1

phosphorylation

up-regulates

0.563

Using mutagenesis on recombinant peptides, we identified the residue y1176 located in the calpain cleavage site of alpha ii-spectrin, near the sh3 domain, as an in vitro substrate for src kinase and lmw-ptp a. phosphorylation of this residue decreases spectrin sensitivity to calpain in vitro.

SIGNOR-86718

P13762

Q8TCQ1

0

polyubiquitination

down-regulates quantity by destabilization

0.2

Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination.

SIGNOR-271409

P45985

Q9H3Y6

0

phosphorylation

down-regulates activity

0.2

SRMS directly phosphorylates MKK4 and inhibits MKK4-JNK-c-Jun activation upon platinum treatment. Platinum treatment-induced ROS activates SRMS, which inhibits MKK4 kinase activity by directly phosphorylating MKK4 at Y269 and Y307, and consequently attenuates MKK4-JNK activation.

SIGNOR-277902

Q9NPB6

P41743

0

phosphorylation

up-regulates quantity by stabilization

0.866

APKC associates and phosphorylates Par6 on S345. aPKC expression stabilizes Par6 protein levels. We show that the aPKC, PKCι, interacts with TGF-β receptors through Par6 and that these proteins localize to the leading edge of migrating cells. Furthermore, Par6 phosphorylation on serine 345 by TGF-β receptors is enhanced in the presence of aPKC. aPKC kinase activity, as well as an association with Par6, were found to be important for Par6 phosphorylation.

SIGNOR-276432

P21333

P17612

0

phosphorylation

up-regulates

0.2

Site-directed mutagenesis analysis indicated that serine 2152 is the unique substrate in the c-terminal region of abp for endogenously activated pka.

SIGNOR-126659

Q14934

P51812

0

phosphorylation

up-regulates

0.385

The results indicated that rsk2 phosphorylated two additional sites at ser289 (peptide 2) and ser344 (peptide 3)rsk2 induced nuclear localization of nfat3. Rsk2 phosphorylated nfat3 in vitro (km=3.559 microm), and activation of nfat3 by rsk2 enhanced the promoter activity of nfat3 downstream target genes in vivo.

SIGNOR-234473

Q9Y4X5

Q9NZQ7

1

polyubiquitination

down-regulates quantity by destabilization

0.2

We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation.

SIGNOR-277553

P46527

P31749

0

phosphorylation

down-regulates

0.85

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

SIGNOR-88294

P63000

Q8N1I0

0

guanine nucleotide exchange factor

up-regulates activity

0.586

DOCK4 (dedicator for cytokinesis 4), a guanine nucleotide exchange factor (GEF) for the small GTPase Rac1, is one of few genes that are associated with both ASD and dyslexia.

SIGNOR-266823

Q13131

Q14694

1

phosphorylation

up-regulates activity

0.309

Under energy stress, USP10 activity in turn is enhanced through AMPK-mediated phosphorylation of Ser76 of USP10.

SIGNOR-277207

O15269

P00519

0

phosphorylation

down-regulates

0.2

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

SIGNOR-202003

P01116

Q06124

0

dephosphorylation

up-regulates activity

0.66

Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling.

SIGNOR-255982

Q7Z628

Q13153

0

phosphorylation

down-regulates activity

0.249

In this work we show that the Rac/Cdc42hs-regulated protein kinase PAK1 down-regulates the activity of the RhoA-specific guanine nucleotide exchange factor NET1. Specifically, PAK1 phosphorylates NET1 on three sites in vitro: serines 152, 153, and 538. Replacement of serines 152 and 153 with glutamate residues down-regulates the activity of NET1 as an exchange factor in vitro and its ability to stimulate actin stress fiber formation in cells. Using a phospho-specific antibody that recognizes NET1 phosphorylated on serine 152, we show that PAK1 phosphorylates NET1 on this site in cells and that Rac1 stimulates serine 152 phosphorylation in a PAK1-dependent manner.

SIGNOR-263018

P24941

Q05209

1

phosphorylation

down-regulates activity

0.382

In the present study, we found that S19 site phosphorylation of PTPN12 by CDK2 discharged its antitumor activity by down-regulation of its inhibitory role in cell migration, but not affecting its other regulatory functions.

SIGNOR-277366

Q05513

P05023

1

phosphorylation

up-regulates activity

0.2

Na,K-ATPase alpha(1) subunit was phosphorylated by PKC in hypoxia-treated AEC. In AEC treated with a PKC-zeta antagonist peptide or with the Na,K-ATPase alpha(1) subunit lacking the PKC phosphorylation site (Ser-18), hypoxia failed to decrease Na,K-ATPase abundance and function.

SIGNOR-263181

Q96AX9

Q13224

1

ubiquitination

down-regulates quantity

0.366

Mib2 is localized to the PSD of dendrites in hippocampal neurons and directly ubiquitinates GluN2B in a manner dependent on the non receptor tyrosine kinase Fyn.|These findings suggest that Mib2 mediates proteasome dependent degradation of GluN2B subunits, which may provide a reciprocal mechanism to SCF Fbx2 regulation of GluN2A.

SIGNOR-278762

Q9UQ88

Q13153

1

phosphorylation

up-regulates activity

0.384

CDK11p58 phosphorylation of PAK1 Ser174 promotes DLC2 binding and roles on cell cycle progression|We show that PAK1 is a substrate of CDK11p58 and can be strongly activated upon phosphorylation.

SIGNOR-273026

P51955

Q12834

1

phosphorylation

up-regulates activity

0.945

In summary, we have demonstrated that Nek2 can associate with and phosphorylate Mad2 and Cdc20.|The results presented here support a model in which Nek2 modulates the functions of Mad2 and Cdc20 in the mitotic checkpoint and elevation of Nek2 levels may contribute to chromosome instability by interfering with the control of the checkpoint.

SIGNOR-278366

P05771

P41180

1

phosphorylation

down-regulates activity

0.319

Expression of a mutant CaR in which the major PKC phosphorylation site is altered by substitution of alanine for threonine (T888A) eliminated oscillatory behavior, producing [Ca(2+)](i) responses almost identical to those produced by the wild type CaR exposed to PKC inhibitors. These results support a model in which phosphorylation of the CaR at the inhibitory threonine 888 by PKC provides the negative feedback needed to cause [Ca(2+)](i) oscillations mediated by this receptor.

SIGNOR-249176

P07203

P42684

0

phosphorylation

up-regulates activity

0.322

GPx1 also functions as a substrate for c-Abl- and Arg-mediated phosphorylation on Tyr-96. The results further show that c-Abl and Arg stimulate GPx activity and that these kinases contribute to GPx-mediated protection of cells against oxidative stress.

SIGNOR-104328

P35222

P31749

0

phosphorylation

up-regulates

0.805

Phosphorylation of beta-catenin by akt promotes beta-catenin transcriptional activity|we have demonstrated that akt phosphorylates beta-catenin at ser552 in vitro and in vivo.

SIGNOR-252499

P01106

P62633

0

transcriptional regulation

down-regulates quantity by repression

0.303

These data verified that the binding of CNBP with c-myc promoter G-quadruplex can indeed down-regulate its associated gene expression for a certain period of time. This result with human CNBP is somehow consistent with previous reports that c-myc G-quadruplex serves as a silencer of c-myc transcription [7] and CNBP promotes the formation of c-myc G-quadruplex.

SIGNOR-261571

P25963

P51812

0

phosphorylation

down-regulates quantity by destabilization

0.368

Here, we show that RSK2 is activated by treatment with tumor necrosis factor-alpha (TNF-alpha) and directly phosphorylates IkappaBalpha at Ser 32, leading to IkappaBalpha degradation.

SIGNOR-279108

Q92831

P68431

1

acetylation

down-regulates activity

0.2

The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.

SIGNOR-269611

P11912

P07948

0

phosphorylation

up-regulates activity

0.738

Y182 of CD79a appears to be the initial and preferred site of Ag receptor phosphorylation by Src family kinases. In vitro, Src family Lyn and Fyn predominantly phosphorylate this residue in CD79a, and Y195 does so in CD79b. phosphorylation of Y182 alone can lead to further kinase activation and/or effector focusing necessary for phosphorylation of certain downstream targets, such as p62, p110, and Shc, but not others, such as Vav.

SIGNOR-251397

P52292

Q13131

0

phosphorylation

up-regulates

0.2

Ampk phosphorylated importin alpha1 on ser(105). Accordingly, expression of importin alpha1 proteins bearing k22r or s105a mutations failed to mediate the nuclear import of hur in intact cells. Our results point to importin alpha1 as a critical downstream target of ampk and key mediator of ampk-triggered hur nuclear import.

SIGNOR-128629

O15169

P36873

0

dephosphorylation

down-regulates activity

0.269

The data suggest that PP1 controls Wnt signaling through interaction with, and regulated dephosphorylation of, axin| Axin phosphorylation markedly enhances the binding of glycogen synthase kinase 3, leading to a more active beta-catenin destruction complex. Wnt-regulated changes in axin phosphorylation, mediated by PP1, may therefore determine beta-catenin transcriptional activity| Four sites, S80, S82, S222, and S473, were identified to be PP1 regulated

SIGNOR-248494

Q8WXG1

Q05516

0

transcriptional regulation

up-regulates quantity by expression

0.2

Promoter regions from the PLZF-regulated transcripts Rsad2 and Ifit2 were fused to luciferase and activity was measured after IFN treatment. Overexpression of PLZF in RCC1 or ACHN cells produced a dose-dependent induction of the reporter promoters.

SIGNOR-261023

Q8NFU7

P31269

1

transcriptional regulation

up-regulates quantity by expression

0.306

Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9.

SIGNOR-259094

Q9BY66

Q16695

1

demethylation

up-regulates activity

0.2

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

SIGNOR-264309

P53350

Q13153

0

phosphorylation

up-regulates

0.552

We show here that pak1 is required for cell proliferation, mitotic progression and plk1 activity in hela cells. phosphorylation of plk1 on ser 49 is important for metaphase-associated events.

SIGNOR-178353

O14965

P23528

1

phosphorylation

down-regulates activity

0.316

However, this study identified that CFL-1 also acts as a direct substrate of Aur-A, which phosphorylates CFL-1 at multiple sites, including S3, S8, and T25, resulting in its inactivation.|In early cell mitotic phases, LIMK1 and Aur-A phosphorylate and inactivate CFL-1, while at the later stages, SSH-1 inactivates LIMK1 and dephosphorylates and activates CFL-1 [33] .

SIGNOR-279798

P28069

Q969G2

0

transcriptional regulation

up-regulates quantity by expression

0.514

We show that normal LHX4 binds to a human-specific element and subsequently activates transcription from the proximal upstream regulatory sequence of POUIF1, a gene encoding a POU homeodomain transcription factor known as the main regulator of GH expression.

SIGNOR-266056

P53041

Q99683

1

dephosphorylation

down-regulates activity

0.597

After exposure of cells to H2O2, ASK1 is transiently activated by autophosphorylation at Thr845. The protein then associates with PP5 (protein serine/threonine phosphatase 5), which inactivates ASK1 by dephosphorylation of Thr845.

SIGNOR-248540

P46937

P49336

0

phosphorylation

up-regulates activity

0.321

CDK8 phosphorylates YAP and promotes its activation. Of interest, mutating four amino acid positions (T119, S128, S289, and S367) to alanines (YAP-4A) completely blocked phosphorylation (Fig. 6J), suggesting that CDK8 phosphorylates these sites in YAP in vitro.

SIGNOR-277651

P53350

Q9P2P6

1

phosphorylation

down-regulates quantity by destabilization

0.309

NI indicates the noninduced control. (B) Plk1 phosphorylates STARD9-motor domain at serine 312.

SIGNOR-279806

Q96SR6

Q8NFU7

0

transcriptional regulation

up-regulates quantity by expression

0.2

Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9.

SIGNOR-259095

Q00987

Q8NEZ5

0

ubiquitination

down-regulates quantity by destabilization

0.2

SCFFBXO22 targets HDM2 for degradation and modulates breast cancer cell invasion and metastasis|we discovered Skp1-Cullin 1-FBXO22-ROC1 (SCFFBXO22) as the most dominating HDM2 E3 ubiquitin ligase from human proteome. The results of protein decay rate analysis, ubiquitination, siRNA-mediated silencing, and coimmunoprecipitation experiments support a hypothesis that FBXO22 targets cellular HDM2 for ubiquitin-dependent degradation.

SIGNOR-273440

P35398

Q8IVA1

1

transcriptional regulation

up-regulates quantity by expression

0.2

RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.

SIGNOR-266849

O94916

Q8N752

0

phosphorylation

up-regulates activity

0.2

However, the siRNA knockdown of CK1α1L significantly reduced the nuclear export of OREBP/TonEBP under hypotonic conditions (Fig. 5F). Taken together, these data suggest that CK1α1L is the kinase that phosphorylates Ser-158 in the regulation of OREBP/TonEBP export.

SIGNOR-274111

P05198

Q86TM6

0

ubiquitination

down-regulates quantity by destabilization

0.2

HRD1 overexpression also decreased the expression of eIF2alpha and p-eIF2alpha in HKC-8 cells.|HRD1 promoted eIF2alpha ubiquitylation and degradation, thereby providing a protective mechanism that suppressed tubular epithelial cell apoptosis.

SIGNOR-278671

P04637

P02511

1

transcriptional regulation

up-regulates quantity by expression

0.47

Aberrant expression of CRYAB has been shown to be associated with several neurological diseases and malignant neoplasms. To identify transcriptional regulators of CRYAB expression, we examined its promoter for binding sites of transcription factors and identified four potential AP-2 binding sites in addition to a p53 binding site reported previously|Taken together, our results indicate that AP-2_ up-regulates the transcription of the CRYAB gene through stabilizing p53

SIGNOR-253638

P04049

Q13118

1

phosphorylation

down-regulates quantity by destabilization

0.2

RAF1 phosphorylates the Thr93 site of KLF10 in vivo. Since the phosphorylation of Thr93 enables KLF10 and PIN1 to bind, it seems likely that RAF-1 will have an effect on KLF10 stability that is similar to that of PIN1.PIN1 facilitates KLF10 protein degradation. (

SIGNOR-276502

Q99626

Q12864

1

transcriptional regulation

up-regulates quantity by expression

0.406

The present study aims to identify the transcription factors which interact and regulate CDH17 promoter activity that might contribute to the up-regulation of CDH17 gene in human HCC|we identified hepatic nuclear factor 1α (HNF1α) and caudal-related homeobox 2 (CDX2) binding sites at the proximal promoter region which modulate the CDH17 promoter activities in two HCC cell lines (Hep3B and MHCC97L)

SIGNOR-253963

P78527

P07954

1

phosphorylation

up-regulates activity

0.2

We show that exposure to ionizing radiation induces DNA-PK-dependent phosphorylation of nuclear fumarase at Thr 236, which leads to an interaction between fumarase and the histone variant H2A.Z at DNA double-strand break (DSB) regions.

SIGNOR-266349

Q13586

Q13153

0

phosphorylation

up-regulates activity

0.354

Taken together, our data demonstrate that PAK1 interacts with STIM1 and phosphorylates specific STIM1 cytosolic domains.

SIGNOR-279244

P45983

O95644

1

phosphorylation

down-regulates activity

0.621

It has been previously shown that NF-ATc1 accumulates in the nucleus of activated CD4 + T cells from Jnk1 \n \u2212/\u2212 mice 35\u2022 and that JNK1 phosphorylates and inactivates NFATc1 in Jurkat T cells 47 , indicating that JNK1 is an inhibitor of NFAT.

SIGNOR-280031

P54296

P17612

0

phosphorylation

down-regulates

0.2

This binding is regulated in vitro by phosphorylation of a single serine residue (ser76) in the immediately adjacent amino-terminal domain mp1. M-protein phosphorylation by camp-dependent kinase a inhibits binding to myosin lmm.

SIGNOR-56395

P35637

Q9UQ80

1

sumoylation

up-regulates activity

0.336

Here, we show that Ebp1 p42 isoform can be sumoylated on both K93 and K298 residues, which mediate its nuclear translocation and are required for its anti-proliferative activity .. Hence, TLS-mediated sumoylation is required for Ebp1 transcriptional repressive activity.

SIGNOR-236904

P08151

P23443

0

phosphorylation

up-regulates

0.523

In this study, we found that an activated mtor/s6k1 pathway promotes gli1 transcriptional activity and oncogenic function through s6k1-mediated gli1 phosphorylation at ser84, which releases gli1 from its endogenous inhibitor, sufu.

SIGNOR-196756

P01909

Q86YJ5

0

ubiquitination

down-regulates quantity by destabilization

0.2

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

SIGNOR-271538

P45983

P38936

1

phosphorylation

up-regulates quantity by stabilization

0.672

The stress-activated protein kinases p38 alpha and jnk1 stabilize p21(cip1) by phosphorylation.|p38 alpha and JNK1 phosphorylated p21 in vivo, and both p38 alpha and JNK1 phosphorylated p21 at Ser(130) in vitro.

SIGNOR-89440

Q13882

P18031

0

dephosphorylation

down-regulates activity

0.575

Using a variety of PTEN mutant constructs, we show that protein phosphatase activity of PTEN targets PTK6, with efficiency similar to PTP1B, a phosphatase that directly dephosphorylates PTK6 Y342.

SIGNOR-277082

P62805

O14929

0

acetylation

down-regulates activity

0.2

Histone acetyltransferase 1 is the founding member of the histone acetyltransferase superfamily and catalyzes lysine acetylation of newly synthesized histone H4|Lys12 for direct attack of the acetyl group of the cofactor.| It is postulated that histone acetylation, through charge neutralization of the cationic histone tails, weakens nucleosomal electrostatic interactions with anionic DNA, thus destabilizing internucleosomal contacts and nucleosomal structure and facilitating access to the promoter region for RNA polymerase and transcription factors.

SIGNOR-264790

P40763

P43405

0

phosphorylation

up-regulates activity

0.552

The current study indicates that the plasma cell malignancy is also associated with Syk-activated STAT3 directly downstream of reelin-induced integrin \u03b21 engagement and FAK/Src activation (Figure xref ).|The integrin-activated spleen tyrosine kinase (Syk) was shown to promote STAT3 phosphorylation [42, 44].

SIGNOR-279298

P02452

Q8IYK4

0

glycosylation

up-regulates activity

0.442

Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.

SIGNOR-261156

O75385

P19367

1

phosphorylation

up-regulates activity

0.257

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

SIGNOR-274033

Q13627

O94826

1

phosphorylation

up-regulates activity

0.2

Phosphorylation of TOM70 Ser91 by DYRK1A stimulates interaction of TOM70 with the core TOM translocase.

SIGNOR-279994

P78559

Q13627

0

phosphorylation

up-regulates activity

0.2

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

SIGNOR-279032

P29353

P35968

0

relocalization

up-regulates activity

0.711

In a similar fashion, KDR associates with Grb2 and Nck in a ligand-dependent fashion, suggesting Shc, Grb2, and Nck as potential candidates involved in the regulation of endothelial function.

SIGNOR-261949

Q9NY46

Q96PU5

0

ubiquitination

down-regulates quantity by destabilization

0.283

The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).

SIGNOR-253464