GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P67870	Q99523	1	phosphorylation	up-regulates quantity by stabilization	0.2	Phosphorylation of Ser-825 is required for insulin to induce Sort1 in AML12 cells. LC-MS/MS analysis further revealed that serine phosphorylation of Sort1 protein was required for insulin induction of Sort1 in a casein kinase 2-dependent manner and that inhibition of PI3K signaling or prevention of Sort1 phosphorylation accelerated proteasome-dependent Sort1 degradation.	SIGNOR-273636
P24864	Q96PU4	0	ubiquitination	down-regulates quantity by destabilization	0.332	We found that NIRF directly ubiquitinated cyclins D1 and E1, as evidenced by the appearance of the tail (Fig. 4B). In summary, the above findings suggest that NIRF tightly cooperates with the core cell cycle machinery and induces G1 arrest, which is accompanied by ubiquitination of cyclins D1 and E1.	SIGNOR-271886
P67775	Q00987	1	dephosphorylation	up-regulates activity	0.455	cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216. Consistent with these data, cyclin G null cells have both Mdm2 that is hyperphosphorylated at T216 and markedly higher levels of p53 protein when compared to wild-type cells	SIGNOR-248636
Q15831	P04637	1	phosphorylation	up-regulates	0.756	We show that lkb1 physically associates with p53 in the nucleus and directly or indirectly phosphorylates p53 ser15 (previously shown to be phosphorylated by amp-dependent kinase) and p53 ser392	SIGNOR-150830
P00533	Q13332	0	dephosphorylation	down-regulates activity	0.43	Similarly, Pestana et al. (89) have reported that overexpression of RPTPsigma in human A431 carcinoma cells partially inhibits EGFR activation, whereas antisense mediated suppression of RPTPsigma expression enhances EGFR activation, substrate phosphorylation, and signalling.\|These data indicate that LAR and RPTPsigma may have a significant role in GPCR induced EGFR signalling.Whereas in A431 cells LAR and RPTPsigma may act to suppress the EGFR in response to GPCR activation, it is possible that the converse may also be true in other cell types.	SIGNOR-277145
P49759	Q07955	1	phosphorylation	up-regulates activity	0.673	In a previous study, we showed that CLK1 phosphorylates SRSF1 to a greater extent than SRPK1, inducing a hyper-phosphorylated state that can be readily detected by a gel shift on SDS-PAGE. xref In xref , the phosphorylation of SRSF1 in single turnover experiments using SRPK1 and CLK1 is shown.\|Unlike SRPK1, CLK1 induces a unique structural form of SRSF1 observed by SDS-PAGE that is exclusively the result of Ser-Pro rather than Arg-Ser phosphorylation.	SIGNOR-279608
Q9ULZ2	Q14289	0	phosphorylation	up-regulates activity	0.352	In 293 cells expressing recombinant BRDG1 and various PTKs, Tec and Pyk2, but not Btk, Bmx, Lyn, Syk, or c-Abl, induced marked phosphorylation of BRDG1 on tyrosine residues. BRDG1 was also phosphorylated by Tec directly in vitro. Furthermore, BRDG1 was shown to participate in a positive feedback loop by increasing the activity of Tec. BRDG1 thus appears to function as a docking protein acting downstream of Tec in BCR signaling.	SIGNOR-261818
Q99962	Q5S007	0	phosphorylation	down-regulates	0.472	We show that lrrk2 affects synaptic endocytosis by phosphorylating endophilin-a1 at s75.	SIGNOR-192072
P17612	P41161	1	phosphorylation	up-regulates activity	0.2	We further show that the increase in erm transcriptional activity after pka phosphorylation is closely correlated with a drastic reduction in the dna binding of the transcription factor. These results indicate that the phosphorylation of erm by pka is involved in erm-mediated transcription and suggest that the activation of erm is probably related to conformational changes.	SIGNOR-111239
P46527	Q06124	0	dephosphorylation	up-regulates activity	0.281	Moreover, SHP-2 was strongly activated on G-CSF stimulation and specifically dephosphorylated p27(Kip1) in vitro.\|Most importantly, we could illustrate that SHP-2 modulates p27 (Kip1) stability and contributes to p27 (Kip1)-mediated cell cycle progression.	SIGNOR-277168
P46977	Q9NZQ7	1	glycosylation	up-regulates quantity by stabilization	0.2	Together, these results support a notion that the two STT3 isoforms regulate EMT-mediated PD-L1 induction through PD-L1 protein N-glycosylation and stabilization.	SIGNOR-274975
P09874	P50876	0	ubiquitination	down-regulates quantity by destabilization	0.2	As RNF144A is a newly characterized E3 ubiquitin ligase , ], we next investigated whether RNF144A could promote PARP1 ubiquitination.\|RNF144A promotes the proteasomal degradation of PARP1.	SIGNOR-278776
Q08945	P68400	0	phosphorylation	down-regulates activity	0.703	CK2 phosphorylates SSRP1 and inhibits its DNA-binding activity. \| we identified serines 510, 657, and 688 as phosphorylation targets of CK2 in vitro. Mutagenesis of the three serines revealed that serine 510 was more important for the regulation of SSRP1 DNA-binding activity.	SIGNOR-250961
Q16566	Q96RR4	0	phosphorylation	up-regulates activity	0.62	Phosphorylation and activation of Ca(2+)-calmodulin-dependent protein kinase IV by Ca(2+)-calmodulin-dependent protein kinase Ia kinase. Phosphorylation of threonine 196 is essential for activation.	SIGNOR-250718
P45985	Q12852	0	phosphorylation	up-regulates activity	0.572	As expected, DLK significantly increased MKK4 phosphorylation on Ser257 / Thr261, and myrAKT1 enhanced MKK4 phosphorylation on Ser78 (XREF_FIG).\|While MKK4 activated by DLK had strong activity in phosphorylating JNK3, MKK4 expressed with DLK and AKT1 together exhibited little activity, even though the two samples had similar levels of Ser257 / Thr261 phosphorylation (XREF_FIG).	SIGNOR-279629
Q16236	Q5RD31	1	transcriptional regulation	up-regulates quantity by expression	0.487	NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.NFE2L2-mediated upregulation of NQO1 is implicated in promoting resistance to ferroptosis inducers, such as erastin and sorafenib, in HCC cells	SIGNOR-279860
P07948	P08575	0	dephosphorylation	down-regulates activity	0.666	CD45 negatively regulates lyn activity by dephosphorylating both positive and negative regulatory tyrosine residues in immature B cells.\| Phosphoamino acid analysis confirmed that Lyn is tyrosine phosphorylated with little serine or threonine phosphorylation. In CD45-negative cells, two bands at 8.2 and 4.1 kDa were phosphorylated in the absence of B cell Ag receptor (BCR) ligation. The 8.2-kDa band corresponded to a fragment containing the positive regulatory site (Tyr397), as assessed by its size and its phosphorylation in an in vitro kinase assay. The 4.1-kDa band was phosphorylated by COOH-terminal Src kinase, suggesting that it contains the COOH-terminal negative regulatory site (Tyr508)	SIGNOR-248354
P12931	O60331	1	phosphorylation	up-regulates	0.285	Phosphorylation by src of the tyrosine adjacent to s650 (y649 in human pipki gamma) was shown to enhance pipki gamma targeting to focal adhesions. We find that y649 phosphorylation does not stimulate directly pipki gamma binding to talin, but may do so indirectly by inhibiting s650 phosphorylation.	SIGNOR-134459
O43379	Q96SN8	0	relocalization	up-regulates activity	0.545	Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome.	SIGNOR-271723
P17612	P54296	1	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
Q8NHW3	P28482	0	phosphorylation	up-regulates activity	0.334	These residues are phosphorylated by erk2 but not by p38, jnk, and erk5 in vitro. However, the contribution of the mek/erk pathway to mafa phosphorylation in vivo appears to be moderate, implicating another kinase. The integrity of serine 14 and serine 65 residues is required for transcriptional activity, since their mutation into alanine severely impairs mafa capacity to activate transcription.	SIGNOR-108564
Q13257	Q96SN8	0	transcriptional regulation	up-regulates quantity by expression	0.309	These data indicate that CDK5RAP2 is a positive regulator of both the BUBR1 promoter and the MAD2 promoter	SIGNOR-260313
P57059	Q15831	0	phosphorylation	up-regulates	0.584	Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold	SIGNOR-122784
P18848	Q15031	1	transcriptional regulation	up-regulates quantity by expression	0.251	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269421
P48058	P17252	0	phosphorylation	up-regulates	0.57	Receptor internalization, altered;intracellular localization	SIGNOR-97554
Q00535	P35611	1	phosphorylation	up-regulates activity	0.255	We found that Cdk5 directly phosphorylated the actin-binding protein adducin-1 (ADD1) at T724 in vitro and in intact cells.	SIGNOR-277487
P46531	Q16665	1	relocalization	up-regulates activity	0.649	The notch intracellular domain interacts with hif-1alpha and hif-1alpha is recruited to notch-responsive promoters upon notch activation under hypoxic conditions.	SIGNOR-141315
Q13485	P63279	0	sumoylation	up-regulates	0.626	The mh1 domain of smad4 was shown to associate physically with ubc9, the ubiquitin carrier protein (e2) conjugating enzyme in sumoylation. In cultured cells, smad4 is modified by sumo-1 at the endogenous level. The sumoylation sites were identified as two evolutionarily conserved lysine residues, lys-113 and lys-159, in the mh1 domain. We found that the mutations at lys-113 and lys-159 did not alter the ability of smad4 to form a complex with smad2 and fast on the mix.2 promoter. Importantly, sumo-1 overexpression enhanced tgf-beta-induced transcriptional responses. These findings identify sumoylation as a unique mechanism to modulate smad4-dependent cellular responses	SIGNOR-98997
Q99538	P78362	0	phosphorylation	up-regulates activity	0.2	Here we report that serine-arginine protein kinase 2 (SRPK2) phosphorylates delta-secretase and enhances its enzymatic activity. SRPK2 phosphorylates serine 226 on delta-secretase and accelerates its autocatalytic cleavage, leading to its cytoplasmic translocation and escalated enzymatic activities.	SIGNOR-273569
P05231	P11831	0	null	up-regulates	0.281	Srf within myofibers modulates Il6 and Cox2/Il4 expressions and, therefore, exerts a paracrine control of satellite cell proliferation and fusion, respectively, which in turn support skeletal muscle hypertrophy.	SIGNOR-255966
Q9UHN6	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-271533
Q8NG27	P15172	0	transcriptional regulation	up-regulates quantity	0.2	... chromatin immunoprecipitation (ChIP) analysis showed MYOD binds to a site upstream the Pja1 promoter preferentially in C2C12 cells induced to differentiate (Fig. 2c). In addition, over-expression of MyoD in human fibroblasts is sufficient to up-regulate Pja1 expression	SIGNOR-255718
Q9BQQ3	P42574	0	cleavage	up-regulates activity	0.396	In contrast, Caspase‐3 cleavage of GRASP‐1 releases the C‐terminal fragment, which in turn activates JNK signaling by serving as a scaffold protein	SIGNOR-260613
Q71DI3	Q92830	0	acetylation	down-regulates activity	0.2	The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.	SIGNOR-269601
O14641	P57078	0	phosphorylation	up-regulates activity	0.44	Co-transfection of a RIPK4-GFP fusion increased the percentage of cells containing DVL2 puncta to more than 75% ( and ), suggesting that RIPK4 facilitates DVL2 signalosome formation.\|Phosphorylation of DVL2 at Ser 298 and Ser 480 by RIPK4 favored canonical Wnt signaling.	SIGNOR-279756
P31751	Q04656	1	phosphorylation	up-regulates quantity by stabilization	0.261	Akt2 (Protein Kinase B Beta) Stabilizes ATP7A, a Copper Transporter for Extracellular Superoxide Dismutase, in Vascular Smooth Muscle: Novel Mechanism to Limit Endothelial Dysfunction in Type 2 Diabetes Mellitus\|Immunoprecipitation, in vitro kinase assay, and mass spectrometry analysis reveal that insulin stimulates Akt2 binding to ATP7A to induce phosphorylation at Ser1424/1463/1466	SIGNOR-272268
O75116	Q15306	1	phosphorylation	up-regulates	0.417	Carock2 phosphorylated irf4 at either of 2 distinct phosphorylation sites, s446 and s447 / rock2-mediated phosphorylation of irf4 regulated the synthesis of il-17 and il-21 and the differentiation of th17 cells.	SIGNOR-167471
Q9Y6I3	P06493	0	phosphorylation	down-regulates activity	0.323	Phosphorylation of POB1 and Epsin by p34cdc2 kinase. Their phosphorylation sites (Ser411 of POB1 and Ser357 of Epsin) were determined. Phosphorylated Epsin and EpsinS357D formed a complex with α-adaptin less efficiently than wild type Epsin.	SIGNOR-262723
P36896	Q15796	1	phosphorylation	up-regulates activity	0.802	ActRIIB, and then partners with a type I receptor, either activin receptor-like kinase 4 (ALK4 or ActRIB) or ALK5 (T²RI), to induce phosphorylation of Smad2/Smad3 and activate a TGF-²-like signaling pathway	SIGNOR-235157
P45985	Q9Y6R4	0	phosphorylation	up-regulates activity	0.568	When truncated mapkkk4 (deltamapkkk4) was overexpressed in hek293 cells, it was constitutively activeco-expressed map kinase kinase (mkk)-1, mkk-4, mkk-3 and mkk-6 were activated in vivo by deltamapkkk4. All of the above mkks purified from escherichia coli were phosphorylated and activated by deltamapkkk4 immunoprecipitates in vitro.	SIGNOR-62369
P17542	P27361	0	phosphorylation	down-regulates	0.357	We report here that the important proangiogenic stimulus hypoxia stimulates phosphorylation, ubiquitination, and proteasomal breakdown of tal1 in endothelial cells. A specific serine in the putative transactivation domain of the protein, ser122, is preferentially phosphorylated by mapk in vitro.	SIGNOR-116153
P49841	Q15831	0	phosphorylation	down-regulates activity	0.378	In this regard, it was shown that LKB1 physically associates with PKC-zeta, which is known to inhibit GSK3beta kinase activity by promoting its phosphorylation.\|Thus, inhibitory phosphorylation of GSK3beta by LKB1 and/or AKT may be a cardinal event leading to constitutive activation of Wnt and beta-catenin signaling (XREF_FIG).	SIGNOR-280148
P11309	Q92934	1	phosphorylation	down-regulates activity	0.371	Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. pim kinases are constitutively active when expressed in HEK-293 cells and are able to phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and Ser155 in vitro and in cells.	SIGNOR-250390
P27816	Q9P0L2	0	phosphorylation	down-regulates activity	0.437	Here we show that p110mark phosphorylates analogous KXGS sites in the microtubule binding domains of the neuronal MAP2 and the ubiquitous MAP4. Phosphorylation in vitro leads to the dissociation of MAP2 and MAP4 from microtubules and to a pronounced increase in dynamic instability.	SIGNOR-250171
P01111	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-183738
Q13153	Q96IF1	1	phosphorylation	up-regulates activity	0.256	The Rac effector PAK1 was also transiently activated upon cell-cell adhesion and directly phosphorylated Ajuba (Thr172).	SIGNOR-278449
O75626	O75925	0	sumoylation	up-regulates	0.324	Blimp_1 is subjected to pias1_mediated sumoylation at lysine 816 / it appears that sumo_modified blimp_1 is a more potent transcriptional repressor.	SIGNOR-197265
P42345	Q13615	0	null	down-regulates activity	0.354	The PtdIns3-phosphatase MTMR3 interacts with mTORC1 and suppresses its activity.	SIGNOR-245105
Q9BYM8	O14867	1	ubiquitination	down-regulates quantity by destabilization	0.345	HOIL-1 bound Bach1 in vivo and thus stimulated its polyubiquitination in vitro. These results suggest that heme regulates the polyubiquitination of Bach1 and subsequent degradation and that HOIL-1 may function as an E3 ligase in this process.	SIGNOR-236971
P00519	P63244	1	phosphorylation	up-regulates	0.2	Phosphorylation of rack1 on tyrosine 52 by c-abl is required for insulin-like growth factor i-mediated regulation of focal adhesion kinase.Tyrosine 52 is further shown to be phosphorylated by c-abl kinase, and the c-abl inhibitor sti571 disrupts fak interaction with rack1	SIGNOR-185649
Q9UNE7	Q9NZQ7	1	destabilization	down-regulates quantity by destabilization	0.2	Deletion of STUB1 resulted in a more profound increase in PD-L1 levels in CMTM6 deficient than in CMTM6 proficient cells, identifying STUB1 as an E3 ligase that causes destabilization of PD-L1 (Fig. 4f,g), either by direct modification of one of the lysines in the PD-L1 cytoplasmic domain or indirectly	SIGNOR-274979
Q9H2K2	Q9Y2T1	1	ADP-ribosylation	down-regulates quantity by destabilization	0.697	Together, these findings are consistent with the hypothesis that TNKS promotes the ubiquitination and degradation of axin, which may be mediated, at least in part, through the direct PARsylation of axin.	SIGNOR-263380
P67870	Q9Y5B0	1	phosphorylation	down-regulates activity	0.327	We found that only phosphorylated FCP1 can physically interact with TFIIF. We set out to purify an FCP1 kinase from HeLa cells and identified casein kinase 2, which, surprisingly, displayed a negative effect on FCP1-associated activities.\| Phosphorylation of FCP1 by CK2 Inhibits the Transcription Elongation Activity of FCP1. \| Two in vivo phosphorylation sites within the C terminus of FCP1 at Ser-575 and Ser-740 were identified	SIGNOR-251064
O94806	Q8WYL5	1	phosphorylation	down-regulates activity	0.286	Active PKD Isoforms Phosphorylate and Inactivate SSH1L\|Here, we show that active PKD3 also mediates SSH1L phosphorylation at Ser-978 and binding to 14-3-3, further confirming the involvement of all three PKD isoforms in negatively regulating this phosphatase	SIGNOR-275938
P05556	O75365	0	dephosphorylation	down-regulates activity	0.527	In this study, we demonstrate that PRL-3 directly binds to integrin \u03b21 and dephosphorylates integrin \u03b21-Y783, a key residue for integrin \u03b21 function [ ].\|These results indicate that PRL-3 dephosphorylates integrin \u03b21 in vitro and in vivo.	SIGNOR-277050
P27816	P06493	0	phosphorylation	down-regulates activity	0.497	We have shown that MAP4 is phosphorylated in vivo in mitotic HeLa cells at eight sites. Five of these were phosphorylated by p34cdc2 kinase. Two of the five p34cdc2 kinase phosphorylation sites were shown to be Ser696 and Ser787 in the proline-rich region. Mutation of Ser787 to Glu strikingly reduced the MAP4's MT-polymerization activity, while Glu-mutation at Ser696 did not. These results suggest that Ser787 could be the critical phosphorylation site causing MTs to be dynamic at mitosis.	SIGNOR-277459
P63279	Q6DJT9	1	sumoylation	down-regulates	0.277	Sumoylation decreases the transcriptional activity of plag1 / plag1 is sumoylated at 2 specific lysine residues (lys-244 and lys-263)	SIGNOR-126048
P28482	P01100	1	phosphorylation	up-regulates activity	0.792	We have recently shown that erk phosphorylates multiple residues within the carboxylterminal transactivation domain (tad) of c-fos, thus resulting in its increased transcriptional activity. ERK2 phosphorylated c-Fos TADs that included Thr- 325, Thr-331, or Ser-374 as unique phospho-acceptor sites, thus indicating that these residues can serve as in vitro targets for the enzymatic activity of ERK2.	SIGNOR-236010
P45983	O43521	1	phosphorylation	down-regulates quantity by destabilization	0.759	Ser69 can also be phosphorylated by JNK and p38MAPK at least in vitro. Phosphorylation of BimEL on Ser69 promotes its ubiquitination.	SIGNOR-250132
P63241	P04637	1	transcriptional regulation	up-regulates quantity by expression	0.364	eIF5A regulated p53 protein expression. Further analysis by reverse transcription PCR showed eIF5A-activated p53 transcription. The effect of eIF5A on p53 transcriptional activity was further demonstrated by the increasing expressions of p21 and Bax, well known target genes of p53.	SIGNOR-266375
Q2TAL8	Q9NSD9	1	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269404
Q02750	P15056	0	phosphorylation	up-regulates activity	0.789	Activation of mek family kinases requires phosphorylation of two conserved ser/thr residueserine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf.	SIGNOR-235475
O00712	P41161	1	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268880
P54764	P10912	1	phosphorylation	up-regulates activity	0.2	EphA4 binds to growth hormone receptor at both its extracellular and intracellular domains and phosphorylates growth hormone receptor when stimulated with a ligand.\|These findings suggest that EphA4 activates not only GHR, as shown above, but also JAK2 by direct phosphorylation.	SIGNOR-279461
P19367	P12931	0	phosphorylation	down-regulates activity	0.492	Mechanistically, c-Src phosphorylation of HK1 at Tyr732 robustly decreases its K m and increases its V max by disrupting its dimer formation.\|Mechanistically, c-Src-mediated Y732 phosphorylation disrupts HK1 dimer formation, alters its enzyme kinetics and eventually enhances enzymatic activity ( ).	SIGNOR-278209
P17676	P28845	1	transcriptional regulation	up-regulates quantity by expression	0.284	In conclusion, C/EBPalpha and C/EBPbeta control basal transcription, and TNF-alpha upregulates 11beta-HSD1, most likely by p38 MAPK-mediated increased binding of C/EBPbeta to the human HSD11B1 promoter.	SIGNOR-268972
Q7Z570	Q13489	1	transcriptional regulation	down-regulates quantity by repression	0.2	ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3).	SIGNOR-269467
Q13428	O60934	1	relocalization	up-regulates activity	0.319	We further identify TCOF1 (also known as Treacle), a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1, and demonstrate that NBS1 translocation and accumulation in the nucleoli is Treacle dependent.	SIGNOR-265085
Q9Y243	P29474	1	phosphorylation	up-regulates activity	0.485	The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites	SIGNOR-251626
Q13627	P08151	1	phosphorylation	up-regulates activity	0.514	Here, we have used an in vitro kinase assay and phospho-peptide mass spectrometry analysis to identify site(s) of direct phosphorylation of GLI1 by DYRK1A and have determined that DYRK1A phosphorylates GLI1 at Ser408 within its nuclear localization sequence.\|The kinase DYRK1A (dual-specificity tyrosine phosphorylation regulated kinase 1a) has been shown to activate GLI1 via a phosphorylation event, leading to the translocation of GLI1 from the cytoplasm to the nucleus .	SIGNOR-278930
P10828	P27361	0	phosphorylation	down-regulates activity	0.428	We concluded that serine 142 of the tr dbd is the likely site of phosphorylation by t(4)-activated mapk and that the docking site on tr for activated mapk includes residues 128-133 (kgffrr), a basic amino acid-enriched motif novel for mapk substrates. Tr mutations in the proposed mapk docking domain and at residue 142 modulated t(4)-conditioned shedding of co-repressor and recruitment of co-activator proteins by the receptor, and they altered transcriptional activity of tr in a thyroid hormone response element-luciferase reporter assay.	SIGNOR-102224
P27361	Q9NYV6	1	phosphorylation	up-regulates	0.2	Erk-dependent phosphorylation of the transcription initiation factor tif-ia is required for rna polymerase i transcription and cell growth. phosphopeptide mapping and mutational analysis reveals two serine residues (s633 and s649) that are phosphorylated by erk and rsk kinases. Replacement of s649 by alanine inactivates tif-ia, inhibits pre-rrna synthesis, and retards cell growth.	SIGNOR-98984
P84243	P31749	0	phosphorylation	down-regulates activity	0.2	Additionally, active akt1 kinase strongly phosphorylates histone h3 at serine 10 in vitro	SIGNOR-98285
Q05193	Q00535	0	phosphorylation	up-regulates activity	0.516	Here, we show that cyclin-dependent kinase 5 (Cdk5) phosphorylates dynamin I on Ser 774 and Ser 778 in vitro, which are identical to its endogenous phosphorylation sites in vivo. Cdk5 antagonists and expression of dominant-negative Cdk5 block phosphorylation of dynamin I, but not of amphiphysin or AP180, in nerve terminals and inhibit SVE.	SIGNOR-250661
Q01196	Q9UPS8	1	transcriptional regulation	down-regulates quantity by repression	0.2	In healthy individual, RUNX1/FLI1 complex negatively regulates ANKRD26 gene expression in MKs.	SIGNOR-266069
Q99683	O60674	0	phosphorylation	down-regulates quantity by destabilization	0.367	Furthermore, JAK2, but not JAK1, directly bound to and phosphorylated ASK1 at Tyr-718, leading to an enhanced association of ASK1 with SOCS1 and subsequent ASK1 degradation.	SIGNOR-276145
P27361	Q86U44	1	phosphorylation	up-regulates quantity by stabilization	0.271	Mass spectrometry analysis showed that ERK phosphorylates METTL3 at three highly conserved residues: S43, S50, and S525 (Figures 2D and 2E). Mutational analysis further confirmed these three sites as main ERK phosphorylation sites (Figure 2F). Phosphorylation of METTL3 increases interaction with USP5, decreasing ubiquitination to stabilize the m6 A methyltransferase complex.	SIGNOR-265949
P42081	Q8TCQ1	0	ubiquitination	down-regulates quantity by destabilization	0.2	Among nine family members examined, forced expression of MARCH1, -2, and -8 induced a significant reduction of surface CD86 in several cell lines.\|CD86 is ubiquitinated by MARCH1.	SIGNOR-278628
P22001	P12931	0	phosphorylation	up-regulates	0.31	The shaker family k+ channel protein, kv1.3, is tyrosine phosphorylated by v-src kinase at tyr137 and tyr449 to modulate current magnitude and kinetic properties.	SIGNOR-114641
P06493	Q13286	1	phosphorylation	down-regulates activity	0.257	(D) Phosphorylation of Cln3 by Cdk1 is independent of Ssa1 T36.\|Thereby, both Cdk1 and Pho85can promote Cln3 degradation, though under distinct circumstances.	SIGNOR-279013
Q13416	P24941	0	phosphorylation	up-regulates	0.756	We also found that horc2p is phosphorylated in vitro by cyclin a/cdk2, specifically at residues thr116 and thr226. These data combined strongly suggest that skp2 promotes horc1p turnover and that the n-terminal domain of horc1p, containing most of the phosphorylation sites and overlapping with one of the skp2-interacting domains, is a regulatory element for horc1p stability.	SIGNOR-116364
P38936	Q96J87	0	post transcriptional regulation	up-regulates quantity by stabilization	0.2	CELF6 binds to the 3'UTR of p21 transcript and increases its mRNA stability. Depletion of CELF6 promotes cell cycle progression, cell proliferation and colony formation whereas overexpression of CELF6 induces G1 phase arrest.	SIGNOR-269044
Q15038	Q9H2X6	0	phosphorylation	down-regulates activity	0.2	In response to DNA damage, HIPK2 phosphorylates DAZAP2 at several Ser/Thr residues including Ser77, which inhibits its HIPK2-degrading function and targets it to the cell nucleus.	SIGNOR-279335
P36873	O95786	1	dephosphorylation	up-regulates activity	0.2	We identified PP1alpha and PP1gamma as primary phosphatases responsible for MDA5 and RIG-I dephosphorylation, leading to their activation.\|endogenous RIG-I and MDA5 that interacted with PP1 exhibited markedly decreased phosphorylation levels at S8 and S88, respectively	SIGNOR-264580
O14965	Q92974	1	phosphorylation	down-regulates activity	0.332	The mitotic kinases Aurora A/B and Cdk1/Cyclin B phosphorylate GEF-H1, thereby inhibiting GEF-H1 catalytic activity.	SIGNOR-276061
Q96SN8	Q76N32	0	relocalization	up-regulates activity	0.452	We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. \|Retention of Cep68 or PCNT in late mitosis prevents the removal of Cep215	SIGNOR-275624
Q8TDD2	P31749	0	phosphorylation	up-regulates	0.423	Akt, a member of the ser-ine/threonine-specific protein kinase, was found to phosphorylate osx and dlx5	SIGNOR-252514
P04049	P53041	0	dephosphorylation	down-regulates activity	0.462	Protein phosphatase 5 (PP5) was identified as an inactivator that associates with Raf-1 on growth factor stimulation and selectively dephosphorylates an essential activating site, Ser 338. The PP5-mediated dephosphorylation of Ser 338 inhibited Raf-1 activity and downstream signalling to MEK	SIGNOR-248537
P68400	Q13283	1	phosphorylation	down-regulates activity	0.239	We also show that casein kinase 2 phosphorylates G3BP1 at serine 149 in vitro and in cells. These data support a role for casein kinase 2 in regulation of protein synthesis by downregulating stress granule formation through G3BP1.CK2 regulates SG disassembly during stress recovery.G3BP1 is among the strongest SG nucleating proteins, and previous work indicated that G3BP1 phosphorylation at S149 restricts stress granule assembly by partly inhibiting G3BP1 oligomerization	SIGNOR-260748
P12956	Q16763	1	relocalization	up-regulates activity	0.347	As shown in Figure 4, we found that Ku70 (Figure 4b) and Ku80 (Figure 4c) co-immunoprecipitated with UBE2S.>Taken together, these results demonstrate that ETO enhances the UBE2S–Ku70 interaction, and UBE2S can be recruited to the same sites of DSBs with Ku70 upon ETO treatment.	SIGNOR-265079
P61586	Q5TG30	0	gtpase-activating protein	down-regulates activity	0.432	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-260496
Q9UNH5	Q7Z569	0	polyubiquitination	up-regulates activity	0.337	Brap2 promotes Lys-63 linked ubiquitination of HsCdc14A. Collectively, these results support the idea that Brap2 facilitates Lys-63 linked ubiquitin modification of HsCdc14A, which may not be targeted for degradation, but mainly for protein–protein interactions or other regulatory functions.	SIGNOR-271777
P06493	Q96GX5	1	phosphorylation	up-regulates activity	0.513	We propose a model in which the initiating event for Gwl activation is phosphorylation by MPF of the proline-directed sites T193 and T206 in the presumptive activation loop	SIGNOR-249653
P51812	P28482	0	phosphorylation	up-regulates	0.728	Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3.	SIGNOR-161518
A8MYZ6	P48729	0	phosphorylation	down-regulates	0.2	Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity.	SIGNOR-183667
P17252	P35568	1	phosphorylation	down-regulates activity	0.386	We show that pkcalpha is likely to be directly involved in ser24 phosphorylation...These observations are entirely consistent with a recent independent study demonstrating that the IRS1-S24D mutant shows impaired insulin-stimulated IR-IRS-1 interactions, tyrosine phosphorylation of IRS-1, recruitment/activation of PI 3-Kinase, and insulin-stimulated Glut4 translocation	SIGNOR-145398
Q9H0K1	Q15831	0	phosphorylation	up-regulates	0.481	A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold.	SIGNOR-122788
P35659	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.437	These data suggest that the E3 ligase SCFFbxw7-α degrades p-DEK in a GSK-3β–dependent manner.Therefore, the phosphorylation of DEK by GSK-3β is a crucial step to mediate Tpm RNA splicing.	SIGNOR-276303
P25963	Q9UKB1	0	ubiquitination	down-regulates	0.542	We report here the identification of an ikappab-ubiquitin (ub) ligase complex containing the f-box/wd40-repeat protein, beta-trcp, a vertebrate homolog of drosophila slimb. beta-trcp binds to ikappabalpha only when the latter is specifically phosphorylated by an ikappab kinase complex. here we provide evidence that lysine residues 21 and 22 serve as the primary sites for signal-induced ubiquitination of i kappa b alpha.	SIGNOR-64317
P39748	P06493	0	phosphorylation	down-regulates activity	0.446	Phosphorylation of human fen1 by cyclin-dependent kinase modulates its role in replication fork regulation.As a functional consequence of phosphorylation by cdk1-cyclin a in vitro, endo- and exonuclease activities of fen1 are reduced whereas its dna binding is not affected.	SIGNOR-103535

P67870

Q99523

1

phosphorylation

up-regulates quantity by stabilization

0.2

Phosphorylation of Ser-825 is required for insulin to induce Sort1 in AML12 cells. LC-MS/MS analysis further revealed that serine phosphorylation of Sort1 protein was required for insulin induction of Sort1 in a casein kinase 2-dependent manner and that inhibition of PI3K signaling or prevention of Sort1 phosphorylation accelerated proteasome-dependent Sort1 degradation.

SIGNOR-273636

P24864

Q96PU4

0

ubiquitination

down-regulates quantity by destabilization

0.332

We found that NIRF directly ubiquitinated cyclins D1 and E1, as evidenced by the appearance of the tail (Fig. 4B). In summary, the above findings suggest that NIRF tightly cooperates with the core cell cycle machinery and induces G1 arrest, which is accompanied by ubiquitination of cyclins D1 and E1.

SIGNOR-271886

P67775

Q00987

1

dephosphorylation

up-regulates activity

0.455

cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216. Consistent with these data, cyclin G null cells have both Mdm2 that is hyperphosphorylated at T216 and markedly higher levels of p53 protein when compared to wild-type cells

SIGNOR-248636

Q15831

P04637

1

phosphorylation

up-regulates

0.756

We show that lkb1 physically associates with p53 in the nucleus and directly or indirectly phosphorylates p53 ser15 (previously shown to be phosphorylated by amp-dependent kinase) and p53 ser392

SIGNOR-150830

P00533

Q13332

0

dephosphorylation

down-regulates activity

0.43

Similarly, Pestana et al. (89) have reported that overexpression of RPTPsigma in human A431 carcinoma cells partially inhibits EGFR activation, whereas antisense mediated suppression of RPTPsigma expression enhances EGFR activation, substrate phosphorylation, and signalling.|These data indicate that LAR and RPTPsigma may have a significant role in GPCR induced EGFR signalling.Whereas in A431 cells LAR and RPTPsigma may act to suppress the EGFR in response to GPCR activation, it is possible that the converse may also be true in other cell types.

SIGNOR-277145

P49759

Q07955

1

phosphorylation

up-regulates activity

0.673

In a previous study, we showed that CLK1 phosphorylates SRSF1 to a greater extent than SRPK1, inducing a hyper-phosphorylated state that can be readily detected by a gel shift on SDS-PAGE. xref In xref , the phosphorylation of SRSF1 in single turnover experiments using SRPK1 and CLK1 is shown.|Unlike SRPK1, CLK1 induces a unique structural form of SRSF1 observed by SDS-PAGE that is exclusively the result of Ser-Pro rather than Arg-Ser phosphorylation.

SIGNOR-279608

Q9ULZ2

Q14289

0

phosphorylation

up-regulates activity

0.352

In 293 cells expressing recombinant BRDG1 and various PTKs, Tec and Pyk2, but not Btk, Bmx, Lyn, Syk, or c-Abl, induced marked phosphorylation of BRDG1 on tyrosine residues. BRDG1 was also phosphorylated by Tec directly in vitro. Furthermore, BRDG1 was shown to participate in a positive feedback loop by increasing the activity of Tec. BRDG1 thus appears to function as a docking protein acting downstream of Tec in BCR signaling.

SIGNOR-261818

Q99962

Q5S007

0

phosphorylation

down-regulates

0.472

We show that lrrk2 affects synaptic endocytosis by phosphorylating endophilin-a1 at s75.

SIGNOR-192072

P17612

P41161

1

phosphorylation

up-regulates activity

0.2

We further show that the increase in erm transcriptional activity after pka phosphorylation is closely correlated with a drastic reduction in the dna binding of the transcription factor. These results indicate that the phosphorylation of erm by pka is involved in erm-mediated transcription and suggest that the activation of erm is probably related to conformational changes.

SIGNOR-111239

P46527

Q06124

0

dephosphorylation

up-regulates activity

0.281

Moreover, SHP-2 was strongly activated on G-CSF stimulation and specifically dephosphorylated p27(Kip1) in vitro.|Most importantly, we could illustrate that SHP-2 modulates p27 (Kip1) stability and contributes to p27 (Kip1)-mediated cell cycle progression.

SIGNOR-277168

P46977

Q9NZQ7

1

glycosylation

up-regulates quantity by stabilization

0.2

Together, these results support a notion that the two STT3 isoforms regulate EMT-mediated PD-L1 induction through PD-L1 protein N-glycosylation and stabilization.

SIGNOR-274975

P09874

P50876

0

ubiquitination

down-regulates quantity by destabilization

0.2

As RNF144A is a newly characterized E3 ubiquitin ligase , ], we next investigated whether RNF144A could promote PARP1 ubiquitination.|RNF144A promotes the proteasomal degradation of PARP1.

SIGNOR-278776

Q08945

P68400

0

phosphorylation

down-regulates activity

0.703

CK2 phosphorylates SSRP1 and inhibits its DNA-binding activity. | we identified serines 510, 657, and 688 as phosphorylation targets of CK2 in vitro. Mutagenesis of the three serines revealed that serine 510 was more important for the regulation of SSRP1 DNA-binding activity.

SIGNOR-250961

Q16566

Q96RR4

0

phosphorylation

up-regulates activity

0.62

Phosphorylation and activation of Ca(2+)-calmodulin-dependent protein kinase IV by Ca(2+)-calmodulin-dependent protein kinase Ia kinase. Phosphorylation of threonine 196 is essential for activation.

SIGNOR-250718

P45985

Q12852

0

phosphorylation

up-regulates activity

0.572

As expected, DLK significantly increased MKK4 phosphorylation on Ser257 / Thr261, and myrAKT1 enhanced MKK4 phosphorylation on Ser78 (XREF_FIG).|While MKK4 activated by DLK had strong activity in phosphorylating JNK3, MKK4 expressed with DLK and AKT1 together exhibited little activity, even though the two samples had similar levels of Ser257 / Thr261 phosphorylation (XREF_FIG).

SIGNOR-279629

Q16236

Q5RD31

1

transcriptional regulation

up-regulates quantity by expression

0.487

NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.NFE2L2-mediated upregulation of NQO1 is implicated in promoting resistance to ferroptosis inducers, such as erastin and sorafenib, in HCC cells

SIGNOR-279860

P07948

P08575

0

dephosphorylation

down-regulates activity

0.666

CD45 negatively regulates lyn activity by dephosphorylating both positive and negative regulatory tyrosine residues in immature B cells.| Phosphoamino acid analysis confirmed that Lyn is tyrosine phosphorylated with little serine or threonine phosphorylation. In CD45-negative cells, two bands at 8.2 and 4.1 kDa were phosphorylated in the absence of B cell Ag receptor (BCR) ligation. The 8.2-kDa band corresponded to a fragment containing the positive regulatory site (Tyr397), as assessed by its size and its phosphorylation in an in vitro kinase assay. The 4.1-kDa band was phosphorylated by COOH-terminal Src kinase, suggesting that it contains the COOH-terminal negative regulatory site (Tyr508)

SIGNOR-248354

P12931

O60331

1

phosphorylation

up-regulates

0.285

Phosphorylation by src of the tyrosine adjacent to s650 (y649 in human pipki gamma) was shown to enhance pipki gamma targeting to focal adhesions. We find that y649 phosphorylation does not stimulate directly pipki gamma binding to talin, but may do so indirectly by inhibiting s650 phosphorylation.

SIGNOR-134459

O43379

Q96SN8

0

relocalization

up-regulates activity

0.545

Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome.

SIGNOR-271723

P17612

P54296

1

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

Q8NHW3

P28482

0

phosphorylation

up-regulates activity

0.334

These residues are phosphorylated by erk2 but not by p38, jnk, and erk5 in vitro. However, the contribution of the mek/erk pathway to mafa phosphorylation in vivo appears to be moderate, implicating another kinase. The integrity of serine 14 and serine 65 residues is required for transcriptional activity, since their mutation into alanine severely impairs mafa capacity to activate transcription.

SIGNOR-108564

Q13257

Q96SN8

0

transcriptional regulation

up-regulates quantity by expression

0.309

These data indicate that CDK5RAP2 is a positive regulator of both the BUBR1 promoter and the MAD2 promoter

SIGNOR-260313

P57059

Q15831

0

phosphorylation

up-regulates

0.584

Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold

SIGNOR-122784

P18848

Q15031

1

transcriptional regulation

up-regulates quantity by expression

0.251

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269421

P48058

P17252

0

phosphorylation

up-regulates

0.57

Receptor internalization, altered;intracellular localization

SIGNOR-97554

Q00535

P35611

1

phosphorylation

up-regulates activity

0.255

We found that Cdk5 directly phosphorylated the actin-binding protein adducin-1 (ADD1) at T724 in vitro and in intact cells.

SIGNOR-277487

P46531

Q16665

1

relocalization

up-regulates activity

0.649

The notch intracellular domain interacts with hif-1alpha and hif-1alpha is recruited to notch-responsive promoters upon notch activation under hypoxic conditions.

SIGNOR-141315

Q13485

P63279

0

sumoylation

up-regulates

0.626

The mh1 domain of smad4 was shown to associate physically with ubc9, the ubiquitin carrier protein (e2) conjugating enzyme in sumoylation. In cultured cells, smad4 is modified by sumo-1 at the endogenous level. The sumoylation sites were identified as two evolutionarily conserved lysine residues, lys-113 and lys-159, in the mh1 domain. We found that the mutations at lys-113 and lys-159 did not alter the ability of smad4 to form a complex with smad2 and fast on the mix.2 promoter. Importantly, sumo-1 overexpression enhanced tgf-beta-induced transcriptional responses. These findings identify sumoylation as a unique mechanism to modulate smad4-dependent cellular responses

SIGNOR-98997

Q99538

P78362

0

phosphorylation

up-regulates activity

0.2

Here we report that serine-arginine protein kinase 2 (SRPK2) phosphorylates delta-secretase and enhances its enzymatic activity. SRPK2 phosphorylates serine 226 on delta-secretase and accelerates its autocatalytic cleavage, leading to its cytoplasmic translocation and escalated enzymatic activities.

SIGNOR-273569

P05231

P11831

0

null

up-regulates

0.281

Srf within myofibers modulates Il6 and Cox2/Il4 expressions and, therefore, exerts a paracrine control of satellite cell proliferation and fusion, respectively, which in turn support skeletal muscle hypertrophy.

SIGNOR-255966

Q9UHN6

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-271533

Q8NG27

P15172

0

transcriptional regulation

up-regulates quantity

0.2

... chromatin immunoprecipitation (ChIP) analysis showed MYOD binds to a site upstream the Pja1 promoter preferentially in C2C12 cells induced to differentiate (Fig. 2c). In addition, over-expression of MyoD in human fibroblasts is sufficient to up-regulate Pja1 expression

SIGNOR-255718

Q9BQQ3

P42574

0

cleavage

up-regulates activity

0.396

In contrast, Caspase‐3 cleavage of GRASP‐1 releases the C‐terminal fragment, which in turn activates JNK signaling by serving as a scaffold protein

SIGNOR-260613

Q71DI3

Q92830

0

acetylation

down-regulates activity

0.2

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

SIGNOR-269601

O14641

P57078

0

phosphorylation

up-regulates activity

0.44

Co-transfection of a RIPK4-GFP fusion increased the percentage of cells containing DVL2 puncta to more than 75% ( and ), suggesting that RIPK4 facilitates DVL2 signalosome formation.|Phosphorylation of DVL2 at Ser 298 and Ser 480 by RIPK4 favored canonical Wnt signaling.

SIGNOR-279756

P31751

Q04656

1

phosphorylation

up-regulates quantity by stabilization

0.261

Akt2 (Protein Kinase B Beta) Stabilizes ATP7A, a Copper Transporter for Extracellular Superoxide Dismutase, in Vascular Smooth Muscle: Novel Mechanism to Limit Endothelial Dysfunction in Type 2 Diabetes Mellitus|Immunoprecipitation, in vitro kinase assay, and mass spectrometry analysis reveal that insulin stimulates Akt2 binding to ATP7A to induce phosphorylation at Ser1424/1463/1466

SIGNOR-272268

O75116

Q15306

1

phosphorylation

up-regulates

0.417

Carock2 phosphorylated irf4 at either of 2 distinct phosphorylation sites, s446 and s447 / rock2-mediated phosphorylation of irf4 regulated the synthesis of il-17 and il-21 and the differentiation of th17 cells.

SIGNOR-167471

Q9Y6I3

P06493

0

phosphorylation

down-regulates activity

0.323

Phosphorylation of POB1 and Epsin by p34cdc2 kinase. Their phosphorylation sites (Ser411 of POB1 and Ser357 of Epsin) were determined. Phosphorylated Epsin and EpsinS357D formed a complex with α-adaptin less efficiently than wild type Epsin.

SIGNOR-262723

P36896

Q15796

1

phosphorylation

up-regulates activity

0.802

ActRIIB, and then partners with a type I receptor, either activin receptor-like kinase 4 (ALK4 or ActRIB) or ALK5 (T²RI), to induce phosphorylation of Smad2/Smad3 and activate a TGF-²-like signaling pathway

SIGNOR-235157

P45985

Q9Y6R4

0

phosphorylation

up-regulates activity

0.568

When truncated mapkkk4 (deltamapkkk4) was overexpressed in hek293 cells, it was constitutively activeco-expressed map kinase kinase (mkk)-1, mkk-4, mkk-3 and mkk-6 were activated in vivo by deltamapkkk4. All of the above mkks purified from escherichia coli were phosphorylated and activated by deltamapkkk4 immunoprecipitates in vitro.

SIGNOR-62369

P17542

P27361

0

phosphorylation

down-regulates

0.357

We report here that the important proangiogenic stimulus hypoxia stimulates phosphorylation, ubiquitination, and proteasomal breakdown of tal1 in endothelial cells. A specific serine in the putative transactivation domain of the protein, ser122, is preferentially phosphorylated by mapk in vitro.

SIGNOR-116153

P49841

Q15831

0

phosphorylation

down-regulates activity

0.378

In this regard, it was shown that LKB1 physically associates with PKC-zeta, which is known to inhibit GSK3beta kinase activity by promoting its phosphorylation.|Thus, inhibitory phosphorylation of GSK3beta by LKB1 and/or AKT may be a cardinal event leading to constitutive activation of Wnt and beta-catenin signaling (XREF_FIG).

SIGNOR-280148

P11309

Q92934

1

phosphorylation

down-regulates activity

0.371

Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. pim kinases are constitutively active when expressed in HEK-293 cells and are able to phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and Ser155 in vitro and in cells.

SIGNOR-250390

P27816

Q9P0L2

0

phosphorylation

down-regulates activity

0.437

Here we show that p110mark phosphorylates analogous KXGS sites in the microtubule binding domains of the neuronal MAP2 and the ubiquitous MAP4. Phosphorylation in vitro leads to the dissociation of MAP2 and MAP4 from microtubules and to a pronounced increase in dynamic instability.

SIGNOR-250171

P01111

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-183738

Q13153

Q96IF1

1

phosphorylation

up-regulates activity

0.256

The Rac effector PAK1 was also transiently activated upon cell-cell adhesion and directly phosphorylated Ajuba (Thr172).

SIGNOR-278449

O75626

O75925

0

sumoylation

up-regulates

0.324

Blimp_1 is subjected to pias1_mediated sumoylation at lysine 816 / it appears that sumo_modified blimp_1 is a more potent transcriptional repressor.

SIGNOR-197265

P42345

Q13615

0

null

down-regulates activity

0.354

The PtdIns3-phosphatase MTMR3 interacts with mTORC1 and suppresses its activity.

SIGNOR-245105

Q9BYM8

O14867

1

ubiquitination

down-regulates quantity by destabilization

0.345

HOIL-1 bound Bach1 in vivo and thus stimulated its polyubiquitination in vitro. These results suggest that heme regulates the polyubiquitination of Bach1 and subsequent degradation and that HOIL-1 may function as an E3 ligase in this process.

SIGNOR-236971

P00519

P63244

1

phosphorylation

up-regulates

0.2

Phosphorylation of rack1 on tyrosine 52 by c-abl is required for insulin-like growth factor i-mediated regulation of focal adhesion kinase.Tyrosine 52 is further shown to be phosphorylated by c-abl kinase, and the c-abl inhibitor sti571 disrupts fak interaction with rack1

SIGNOR-185649

Q9UNE7

Q9NZQ7

1

destabilization

down-regulates quantity by destabilization

0.2

Deletion of STUB1 resulted in a more profound increase in PD-L1 levels in CMTM6 deficient than in CMTM6 proficient cells, identifying STUB1 as an E3 ligase that causes destabilization of PD-L1 (Fig. 4f,g), either by direct modification of one of the lysines in the PD-L1 cytoplasmic domain or indirectly

SIGNOR-274979

Q9H2K2

Q9Y2T1

1

ADP-ribosylation

down-regulates quantity by destabilization

0.697

Together, these findings are consistent with the hypothesis that TNKS promotes the ubiquitination and degradation of axin, which may be mediated, at least in part, through the direct PARsylation of axin.

SIGNOR-263380

P67870

Q9Y5B0

1

phosphorylation

down-regulates activity

0.327

We found that only phosphorylated FCP1 can physically interact with TFIIF. We set out to purify an FCP1 kinase from HeLa cells and identified casein kinase 2, which, surprisingly, displayed a negative effect on FCP1-associated activities.| Phosphorylation of FCP1 by CK2 Inhibits the Transcription Elongation Activity of FCP1. | Two in vivo phosphorylation sites within the C terminus of FCP1 at Ser-575 and Ser-740 were identified

SIGNOR-251064

O94806

Q8WYL5

1

phosphorylation

down-regulates activity

0.286

Active PKD Isoforms Phosphorylate and Inactivate SSH1L|Here, we show that active PKD3 also mediates SSH1L phosphorylation at Ser-978 and binding to 14-3-3, further confirming the involvement of all three PKD isoforms in negatively regulating this phosphatase

SIGNOR-275938

P05556

O75365

0

dephosphorylation

down-regulates activity

0.527

In this study, we demonstrate that PRL-3 directly binds to integrin \u03b21 and dephosphorylates integrin \u03b21-Y783, a key residue for integrin \u03b21 function [ ].|These results indicate that PRL-3 dephosphorylates integrin \u03b21 in vitro and in vivo.

SIGNOR-277050

P27816

P06493

0

phosphorylation

down-regulates activity

0.497

We have shown that MAP4 is phosphorylated in vivo in mitotic HeLa cells at eight sites. Five of these were phosphorylated by p34cdc2 kinase. Two of the five p34cdc2 kinase phosphorylation sites were shown to be Ser696 and Ser787 in the proline-rich region. Mutation of Ser787 to Glu strikingly reduced the MAP4's MT-polymerization activity, while Glu-mutation at Ser696 did not. These results suggest that Ser787 could be the critical phosphorylation site causing MTs to be dynamic at mitosis.

SIGNOR-277459

P63279

Q6DJT9

1

sumoylation

down-regulates

0.277

Sumoylation decreases the transcriptional activity of plag1 / plag1 is sumoylated at 2 specific lysine residues (lys-244 and lys-263)

SIGNOR-126048

P28482

P01100

1

phosphorylation

up-regulates activity

0.792

We have recently shown that erk phosphorylates multiple residues within the carboxylterminal transactivation domain (tad) of c-fos, thus resulting in its increased transcriptional activity. ERK2 phosphorylated c-Fos TADs that included Thr- 325, Thr-331, or Ser-374 as unique phospho-acceptor sites, thus indicating that these residues can serve as in vitro targets for the enzymatic activity of ERK2.

SIGNOR-236010

P45983

O43521

1

phosphorylation

down-regulates quantity by destabilization

0.759

Ser69 can also be phosphorylated by JNK and p38MAPK at least in vitro. Phosphorylation of BimEL on Ser69 promotes its ubiquitination.

SIGNOR-250132

P63241

P04637

1

transcriptional regulation

up-regulates quantity by expression

0.364

eIF5A regulated p53 protein expression. Further analysis by reverse transcription PCR showed eIF5A-activated p53 transcription. The effect of eIF5A on p53 transcriptional activity was further demonstrated by the increasing expressions of p21 and Bax, well known target genes of p53.

SIGNOR-266375

Q2TAL8

Q9NSD9

1

transcriptional regulation

up-regulates quantity by expression

0.2

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269404

Q02750

P15056

0

phosphorylation

up-regulates activity

0.789

Activation of mek family kinases requires phosphorylation of two conserved ser/thr residueserine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf.

SIGNOR-235475

O00712

P41161

1

transcriptional regulation

down-regulates quantity

0.2

By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development

SIGNOR-268880

P54764

P10912

1

phosphorylation

up-regulates activity

0.2

EphA4 binds to growth hormone receptor at both its extracellular and intracellular domains and phosphorylates growth hormone receptor when stimulated with a ligand.|These findings suggest that EphA4 activates not only GHR, as shown above, but also JAK2 by direct phosphorylation.

SIGNOR-279461

P19367

P12931

0

phosphorylation

down-regulates activity

0.492

Mechanistically, c-Src phosphorylation of HK1 at Tyr732 robustly decreases its K m and increases its V max by disrupting its dimer formation.|Mechanistically, c-Src-mediated Y732 phosphorylation disrupts HK1 dimer formation, alters its enzyme kinetics and eventually enhances enzymatic activity ( ).

SIGNOR-278209

P17676

P28845

1

transcriptional regulation

up-regulates quantity by expression

0.284

In conclusion, C/EBPalpha and C/EBPbeta control basal transcription, and TNF-alpha upregulates 11beta-HSD1, most likely by p38 MAPK-mediated increased binding of C/EBPbeta to the human HSD11B1 promoter.

SIGNOR-268972

Q7Z570

Q13489

1

transcriptional regulation

down-regulates quantity by repression

0.2

ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3).

SIGNOR-269467

Q13428

O60934

1

relocalization

up-regulates activity

0.319

We further identify TCOF1 (also known as Treacle), a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1, and demonstrate that NBS1 translocation and accumulation in the nucleoli is Treacle dependent.

SIGNOR-265085

Q9Y243

P29474

1

phosphorylation

up-regulates activity

0.485

The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites

SIGNOR-251626

Q13627

P08151

1

phosphorylation

up-regulates activity

0.514

Here, we have used an in vitro kinase assay and phospho-peptide mass spectrometry analysis to identify site(s) of direct phosphorylation of GLI1 by DYRK1A and have determined that DYRK1A phosphorylates GLI1 at Ser408 within its nuclear localization sequence.|The kinase DYRK1A (dual-specificity tyrosine phosphorylation regulated kinase 1a) has been shown to activate GLI1 via a phosphorylation event, leading to the translocation of GLI1 from the cytoplasm to the nucleus .

SIGNOR-278930

P10828

P27361

0

phosphorylation

down-regulates activity

0.428

We concluded that serine 142 of the tr dbd is the likely site of phosphorylation by t(4)-activated mapk and that the docking site on tr for activated mapk includes residues 128-133 (kgffrr), a basic amino acid-enriched motif novel for mapk substrates. Tr mutations in the proposed mapk docking domain and at residue 142 modulated t(4)-conditioned shedding of co-repressor and recruitment of co-activator proteins by the receptor, and they altered transcriptional activity of tr in a thyroid hormone response element-luciferase reporter assay.

SIGNOR-102224

P27361

Q9NYV6

1

phosphorylation

up-regulates

0.2

Erk-dependent phosphorylation of the transcription initiation factor tif-ia is required for rna polymerase i transcription and cell growth. phosphopeptide mapping and mutational analysis reveals two serine residues (s633 and s649) that are phosphorylated by erk and rsk kinases. Replacement of s649 by alanine inactivates tif-ia, inhibits pre-rrna synthesis, and retards cell growth.

SIGNOR-98984

P84243

P31749

0

phosphorylation

down-regulates activity

0.2

Additionally, active akt1 kinase strongly phosphorylates histone h3 at serine 10 in vitro

SIGNOR-98285

Q05193

Q00535

0

phosphorylation

up-regulates activity

0.516

Here, we show that cyclin-dependent kinase 5 (Cdk5) phosphorylates dynamin I on Ser 774 and Ser 778 in vitro, which are identical to its endogenous phosphorylation sites in vivo. Cdk5 antagonists and expression of dominant-negative Cdk5 block phosphorylation of dynamin I, but not of amphiphysin or AP180, in nerve terminals and inhibit SVE.

SIGNOR-250661

Q01196

Q9UPS8

1

transcriptional regulation

down-regulates quantity by repression

0.2

In healthy individual, RUNX1/FLI1 complex negatively regulates ANKRD26 gene expression in MKs.

SIGNOR-266069

Q99683

O60674

0

phosphorylation

down-regulates quantity by destabilization

0.367

Furthermore, JAK2, but not JAK1, directly bound to and phosphorylated ASK1 at Tyr-718, leading to an enhanced association of ASK1 with SOCS1 and subsequent ASK1 degradation.

SIGNOR-276145

P27361

Q86U44

1

phosphorylation

up-regulates quantity by stabilization

0.271

Mass spectrometry analysis showed that ERK phosphorylates METTL3 at three highly conserved residues: S43, S50, and S525 (Figures 2D and 2E). Mutational analysis further confirmed these three sites as main ERK phosphorylation sites (Figure 2F). Phosphorylation of METTL3 increases interaction with USP5, decreasing ubiquitination to stabilize the m6 A methyltransferase complex.

SIGNOR-265949

P42081

Q8TCQ1

0

ubiquitination

down-regulates quantity by destabilization

0.2

Among nine family members examined, forced expression of MARCH1, -2, and -8 induced a significant reduction of surface CD86 in several cell lines.|CD86 is ubiquitinated by MARCH1.

SIGNOR-278628

P22001

P12931

0

phosphorylation

up-regulates

0.31

The shaker family k+ channel protein, kv1.3, is tyrosine phosphorylated by v-src kinase at tyr137 and tyr449 to modulate current magnitude and kinetic properties.

SIGNOR-114641

P06493

Q13286

1

phosphorylation

down-regulates activity

0.257

(D) Phosphorylation of Cln3 by Cdk1 is independent of Ssa1 T36.|Thereby, both Cdk1 and Pho85can promote Cln3 degradation, though under distinct circumstances.

SIGNOR-279013

Q13416

P24941

0

phosphorylation

up-regulates

0.756

We also found that horc2p is phosphorylated in vitro by cyclin a/cdk2, specifically at residues thr116 and thr226. These data combined strongly suggest that skp2 promotes horc1p turnover and that the n-terminal domain of horc1p, containing most of the phosphorylation sites and overlapping with one of the skp2-interacting domains, is a regulatory element for horc1p stability.

SIGNOR-116364

P38936

Q96J87

0

post transcriptional regulation

up-regulates quantity by stabilization

0.2

CELF6 binds to the 3'UTR of p21 transcript and increases its mRNA stability. Depletion of CELF6 promotes cell cycle progression, cell proliferation and colony formation whereas overexpression of CELF6 induces G1 phase arrest.

SIGNOR-269044

Q15038

Q9H2X6

0

phosphorylation

down-regulates activity

0.2

In response to DNA damage, HIPK2 phosphorylates DAZAP2 at several Ser/Thr residues including Ser77, which inhibits its HIPK2-degrading function and targets it to the cell nucleus.

SIGNOR-279335

P36873

O95786

1

dephosphorylation

up-regulates activity

0.2

We identified PP1alpha and PP1gamma as primary phosphatases responsible for MDA5 and RIG-I dephosphorylation, leading to their activation.|endogenous RIG-I and MDA5 that interacted with PP1 exhibited markedly decreased phosphorylation levels at S8 and S88, respectively

SIGNOR-264580

O14965

Q92974

1

phosphorylation

down-regulates activity

0.332

The mitotic kinases Aurora A/B and Cdk1/Cyclin B phosphorylate GEF-H1, thereby inhibiting GEF-H1 catalytic activity.

SIGNOR-276061

Q96SN8

Q76N32

0

relocalization

up-regulates activity

0.452

We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. |Retention of Cep68 or PCNT in late mitosis prevents the removal of Cep215

SIGNOR-275624

Q8TDD2

P31749

0

phosphorylation

up-regulates

0.423

Akt, a member of the ser-ine/threonine-specific protein kinase, was found to phosphorylate osx and dlx5

SIGNOR-252514

P04049

P53041

0

dephosphorylation

down-regulates activity

0.462

Protein phosphatase 5 (PP5) was identified as an inactivator that associates with Raf-1 on growth factor stimulation and selectively dephosphorylates an essential activating site, Ser 338. The PP5-mediated dephosphorylation of Ser 338 inhibited Raf-1 activity and downstream signalling to MEK

SIGNOR-248537

P68400

Q13283

1

phosphorylation

down-regulates activity

0.239

We also show that casein kinase 2 phosphorylates G3BP1 at serine 149 in vitro and in cells. These data support a role for casein kinase 2 in regulation of protein synthesis by downregulating stress granule formation through G3BP1.CK2 regulates SG disassembly during stress recovery.G3BP1 is among the strongest SG nucleating proteins, and previous work indicated that G3BP1 phosphorylation at S149 restricts stress granule assembly by partly inhibiting G3BP1 oligomerization

SIGNOR-260748

P12956

Q16763

1

relocalization

up-regulates activity

0.347

As shown in Figure 4, we found that Ku70 (Figure 4b) and Ku80 (Figure 4c) co-immunoprecipitated with UBE2S.>Taken together, these results demonstrate that ETO enhances the UBE2S–Ku70 interaction, and UBE2S can be recruited to the same sites of DSBs with Ku70 upon ETO treatment.

SIGNOR-265079

P61586

Q5TG30

0

gtpase-activating protein

down-regulates activity

0.432

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-260496

Q9UNH5

Q7Z569

0

polyubiquitination

up-regulates activity

0.337

Brap2 promotes Lys-63 linked ubiquitination of HsCdc14A. Collectively, these results support the idea that Brap2 facilitates Lys-63 linked ubiquitin modification of HsCdc14A, which may not be targeted for degradation, but mainly for protein–protein interactions or other regulatory functions.

SIGNOR-271777

P06493

Q96GX5

1

phosphorylation

up-regulates activity

0.513

We propose a model in which the initiating event for Gwl activation is phosphorylation by MPF of the proline-directed sites T193 and T206 in the presumptive activation loop

SIGNOR-249653

P51812

P28482

0

phosphorylation

up-regulates

0.728

Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3.

SIGNOR-161518

A8MYZ6

P48729

0

phosphorylation

down-regulates

0.2

Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity.

SIGNOR-183667

P17252

P35568

1

phosphorylation

down-regulates activity

0.386

We show that pkcalpha is likely to be directly involved in ser24 phosphorylation...These observations are entirely consistent with a recent independent study demonstrating that the IRS1-S24D mutant shows impaired insulin-stimulated IR-IRS-1 interactions, tyrosine phosphorylation of IRS-1, recruitment/activation of PI 3-Kinase, and insulin-stimulated Glut4 translocation

SIGNOR-145398

Q9H0K1

Q15831

0

phosphorylation

up-regulates

0.481

A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold.

SIGNOR-122788

P35659

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.437

These data suggest that the E3 ligase SCFFbxw7-α degrades p-DEK in a GSK-3β–dependent manner.Therefore, the phosphorylation of DEK by GSK-3β is a crucial step to mediate Tpm RNA splicing.

SIGNOR-276303

P25963

Q9UKB1

0

ubiquitination

down-regulates

0.542

We report here the identification of an ikappab-ubiquitin (ub) ligase complex containing the f-box/wd40-repeat protein, beta-trcp, a vertebrate homolog of drosophila slimb. beta-trcp binds to ikappabalpha only when the latter is specifically phosphorylated by an ikappab kinase complex. here we provide evidence that lysine residues 21 and 22 serve as the primary sites for signal-induced ubiquitination of i kappa b alpha.

SIGNOR-64317

P39748

P06493

0

phosphorylation

down-regulates activity

0.446

Phosphorylation of human fen1 by cyclin-dependent kinase modulates its role in replication fork regulation.As a functional consequence of phosphorylation by cdk1-cyclin a in vitro, endo- and exonuclease activities of fen1 are reduced whereas its dna binding is not affected.

SIGNOR-103535