GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q01105-2	P68400	0	phosphorylation	down-regulates	0.365	Ckii-mediated phosphorylation at ser9 hinders nuclear import of set	SIGNOR-200798
O00141	Q6A1A2	0	phosphorylation	up-regulates	0.2	Our results are consistent with a model in which activation of sgk by igf-1 or hydrogen peroxide is initiated by a ptdins(3,4, 5)p3-dependent activation of pdk2, which phosphorylates ser422.	SIGNOR-66234
Q5T447	Q14790	1	polyubiquitination	down-regulates activity	0.336	HECTD3, a new E3 ubiquitin ligase, interacts with caspase-8 death effector domains and ubiquitinates caspase-8 with K63-linked polyubiquitin chains that do not target caspase-8 for degradation but decrease the caspase-8 activation. HECTD3 ubiquitinates caspase-8 with K63-linked polyubiquitin chains at K215.	SIGNOR-272077
P04629	A7KAX9	1	relocalization	up-regulates	0.602	Grit translocation was regulated by receptor stimulation	SIGNOR-95809
Q05655	P49715	1	phosphorylation	down-regulates quantity by destabilization	0.2	We next demonstrated by immunoprecipitation that IL-32\u03b2 interacted with PKC\u03b4 and C/EBP\u03b1, thereby mediating C/EBP\u03b1 Ser-21 phosphorylation by PKC\u03b4.	SIGNOR-279427
Q6ZVD8	P31751	1	dephosphorylation	down-regulates activity	0.604	The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.\|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells.	SIGNOR-248729
Q9UGP8	P67870	0	phosphorylation	up-regulates activity	0.2	Sec63 was identified as a novel substrate and binding partner of protein kinase CK2. We identified serine 574, serine 576 and serine 748 as CK2 phosphorylation sites. Phosphorylation of Sec63 by CK2 enhanced its binding to Sec62.	SIGNOR-265270
O75592	O75385	1	ubiquitination	down-regulates quantity	0.284	Cell-based results demonstrate that the human PHR protein PAM restricts ULK1 protein levels (Fig.\u00a05h, i), and is sufficient to ubiquitinate ULK1 in a proteasome-dependent manner (Fig.\u00a05j).\|Human PAM ubiquitinates ULK1 and regulates ULK1 levels.	SIGNOR-278765
Q9BYB0	O14490	0	relocalization	up-regulates activity	0.2	SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).	SIGNOR-264588
Q9BY84	P28482	0	phosphorylation	up-regulates quantity by stabilization	0.808	Phosphorylation of Ser-446 determines stability of MKP-7.\|We also determined that MKP-7 phosphorylated at Ser-446 has a longer half-life than unphosphorylated form of the wild type protein, as does a phospho-mimic mutant of MKP-7. These results indicate that activation of the ERK pathway strongly blocks JNK activation through stabilization of MKP-7 mediated by phosphorylation.	SIGNOR-249389
P14598	P17252	0	phosphorylation	up-regulates	0.553	Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation.	SIGNOR-89178
Q16539	P06400	1	phosphorylation	down-regulates	0.539	P38 bypasses the cell cycle-associated hierarchical phosphorylation and directly phosphorylates rb on ser567, which is not phosphorylated during the normal cell cycle. Phosphorylation by p38, but not cdks, triggers an interaction between rb and the human homolog of murine double minute 2 (hdm2), leading to degradation of rb, release of e2f1 and cell death.	SIGNOR-168178
O43683	O43684	1	relocalization	up-regulates activity	0.943	Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity	SIGNOR-252019
P17252	O15511	1	phosphorylation	up-regulates activity	0.2	PKC\u03b1 phosphorylates and activates ARPC5, which organizes the actin net dorsolateral of nucleus.	SIGNOR-280078
P24666	P29317	1	dephosphorylation	down-regulates activity	0.66	The SAM domain tyrosine Y960 which has been implicated in downstream PI3K signaling is dephosphorylated exclusively by HCPTP-B. The activation loop tyrosine (Y772) which directly controls kinase activity is dephosphorylated about six times faster by HCPTP-A. In contrast, the juxtamembrane tyrosines (Y575, Y588 and Y594) which are implicated in both control of kinase activity and downstream signaling are dephosphorylated by both variants with similar rates	SIGNOR-246023
P17931	P48729	0	phosphorylation	up-regulates	0.308	These results indicate that phosphorylation of gal-3 promotes its nuclear export after apoptotic stimuli through enhanced nuclear export.	SIGNOR-124583
Q15691	P12931	0	phosphorylation	down-regulates activity	0.2	These data suggest that Src phosphorylates endogenous EB1 at Y247.	SIGNOR-278215
Q9BR76	Q6UB99	0	transcriptional regulation	up-regulates quantity by expression	0.2	Neurite growth-related genes such as Trkb, Bdnf, Gap43, Coronin 1B, and Rab13 are downregulated in ANKRD11-deficient neurons.	SIGNOR-266737
Q9UHV7	P49336	0	phosphorylation	down-regulates quantity by destabilization	0.901	Here, cyclin C-Cdk8 phosphorylation of Med13 most likely primes the phosphodegron for destruction.	SIGNOR-279687
P07948	Q04760	1	phosphorylation	up-regulates activity	0.2	We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).	SIGNOR-276186
Q13153	P29320	0	phosphorylation	up-regulates activity	0.277	Etk kinase directly phosphorylates and activates PAK1 in response to estrogen.\|We demonstrated that estrogen-activated Etk directly phosphorylated PAK1 on Tyr153.	SIGNOR-278398
Q12834	Q96GD4	0	phosphorylation	down-regulates activity	0.767	When SAC is active, Aurora kinase B (AurkB) phosphorylates and inactivates CDC20, to prevent the activation of anaphase promoting complex and cyclosome (APC/C).\|When SAC is active, Aurora kinase B (AurkB) phosphorylates and inactivates CDC20, to prevent the activation of anaphase-promoting complex/cyclosome (APC/C) (Hagting et al., xref ; Nasmyth, xref ; Ruchaud et al., xref ).	SIGNOR-280190
Q9NYV6	Q13131	0	phosphorylation	down-regulates	0.2	We show that ampk down-regulates rrna synthesis under glucose restriction by phosphorylating the rna polymerase i (pol i)-associated transcription factor tif-ia at a single serine residue (ser-635).	SIGNOR-188403
Q13418	Q96C90	1	phosphorylation	up-regulates activity	0.398	We conclude that ILK may activate smooth-muscle contraction both directly, via phosphorylation of myosin, and indirectly, via phosphorylation and activation of CPI-17 and PHI-1, leading to inhibition of MLCP.\|CPI-17 and PHI-1 thiophosphorylated by ILK at Thr(38) or Thr(57) respectively inhibited myosin light-chain phosphatase (MLCP) activity bound to myosin	SIGNOR-265741
P16333	P07766	0	relocalization	up-regulates activity	0.372	We present strong evidence that ligand engagement of TCR-CD3 induces a conformational change that exposes a proline-rich sequence in CD3ϵ and results in recruitment of the adaptor protein Nck.	SIGNOR-259934
P51608	Q06413	1	transcriptional regulation	down-regulates quantity by repression	0.346	MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1.	SIGNOR-264680
P68400	O75676	1	phosphorylation	up-regulates activity	0.281	Here we report that the CK2 protein kinase, which contributes to NF-kappaB activation following UV radiation in a p38-dependent manner, physically interacts with MSK2 but not MSK1 and that CK2 inhibition specifically impairs UV-induced MSK2 kinase activation. A putative site of CK2 phosphorylation was mapped to MSK2 residue Ser(324) and when substituted to alanine (S324A) also compromised MSK2 activity.Serine 324 is required for UV-induced MSK2 activation and for autophosphorylation at MSK2-Ser196.	SIGNOR-276268
P04626	Q9UNE7	0	ubiquitination	down-regulates quantity by destabilization	0.627	The ErbB2 kinase domain is required for GA-induced and CHIP-dependent ErbB2 ubiquitination and degradation .	SIGNOR-278645
Q9GZQ8	Q8TD19	0	phosphorylation	down-regulates activity	0.2	LC3B is phosphorylated at Thr-50 within the LDS by serine/threonine kinase (STK) 3 and STK4. Here, we identified LIR motifs in STK3 and atypical protein kinase Cζ (PKCζ) and never in mitosis A (NIMA)-related kinase 9 (NEK9). All three kinases phosphorylated LC3B Thr-50 in vitro A phospho-mimicking substitution of Thr-50 impaired binding of several LIR-containing proteins, such as ATG4B, FYVE, and coiled-coil domain-containing 1 (FYCO1), and autophagy cargo receptors p62/sequestosome 1 (SQSTM1) and neighbor of BRCA1 gene (NBR1).	SIGNOR-273904
Q9NQU5	P48431	1	phosphorylation	up-regulates quantity	0.2	PAK5 promotes the cell stemness ability by phosphorylating SOX2 in lung squamous cell carcinomas.\|The absence of PAK5 abolishes self-renewal ability of LUSC cells by decreasing the expression and phosphorylation of SOX2 in vitro and in vivo.	SIGNOR-280060
Q92911	Q06710	0	transcriptional regulation	up-regulates quantity by expression	0.408	Pax8 has an essential role in thyroid organogenesis and differentiation, being the main mediator of thyroid gene transcription, including the NIS gene.	SIGNOR-251990
P42345	Q13322	1	phosphorylation	up-regulates	0.412	The adaptor protein grb10 was identified as an mtorc1 substrate that mediates the phosphoinositide 3-kinase.	SIGNOR-174071
Q8TAS1	P16949	1	phosphorylation	down-regulates	0.51	This promigratory phenotype resulted from increased stathmin protein levels, caused by a lack of kis-mediated stathmin phosphorylation at serine 38 and diminished stathmin protein degradation.	SIGNOR-182489
P15172	Q13683	1	transcriptional regulation	up-regulates quantity by expression	0.286	Only myogenin and MyoD were able to efficiently trans-activate the alpha7 promoter-CAT construct (Fig. 7). Myogenin trans-activated the promoter by _2-fold whereas MyoD was able to trans-activate by nearly 4-fold, indicating that both of these factors may play a role in alpha7 gene expression during muscle development.	SIGNOR-241518
P17252	P31431	1	phosphorylation	up-regulates activity	0.732	The phosphorylation state of Ser(183) in the cytoplasmic tail of syndecan-4 determines the binding affinity of the cytoplasmic tail to phosphatidylinositol 4,5-bisphosphate (PIP(2)), the capacity of the tail to multimerize, and its ability to activate protein kinase C (PKC) alpha. We sought to identify the kinase responsible for this phosphorylation and to determine its downstream effects on PKCalpha activity and on endothelial cell function. Among several PKC isoenzymes tested, only PKCalpha and -delta were able to specifically phosphorylate Ser(183) in vitro. However, studies in cultured endothelial cells showed that the phosphorylation level of syndecan-4 was significantly reduced in endothelial cells expressing a dominant negative (DN) PKCdelta but not a DN PKCalpha mutant.	SIGNOR-249149
Q9Y2H1	P14373	0	ubiquitination	up-regulates activity	0.2	TRIM27 catalyzes non-degradative K6- and K11-linked ubiquitination of the serine/threonine kinase 38-like (STK38L) kinase. In turn, STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination of ULK1	SIGNOR-270347
P01584	Q16665	0	transcriptional regulation	up-regulates quantity by expression	0.336	We finally confirmed that in the absence of HIF-1α there was a significant reduction at the protein level in pro-caspase-1, activated caspase-1, pro-IL-1β, and ultimately active IL-1β (Fig. 4g and h). These data show that adenosine induced up-regulation of IL-1β is dependent on a CREB/HIF-1α pathway which is distinct from the NF-kB pathway used for initial production of IL-1β in response to LPS.	SIGNOR-251718
P28562	Q13950	1	dephosphorylation	up-regulates activity	0.353	In a separate study, MKP-1 was shown to induce osteogenesis by dephosphorylating Ser125 on Runx2 isoform type II (37).\|MKP-1 increases RUNX2 activity and downregulates MAPK, cyclin D1 in differentiated osteoblasts inducing growth arrest and mineralization.	SIGNOR-277143
P24941	Q5TZA2	1	phosphorylation	down-regulates	0.2	Finally, phosphorylation of tax1bp2 at serine-763 by cyclin-dependent kinase (cdk)2 abolished the tax1bp2-mediated p38 activation and tumor-suppressive activity, indicating that tax1bp2 can adapt cdk2 signaling to the p38/p53/p21 pathway.	SIGNOR-197593
P28482	Q15672	1	phosphorylation	up-regulates	0.304	We identified the serine 68 (s68) as a major phosphorylation site of twist1 by mass spectrometry and with specific antibodies. This s68 is phosphorylated by p38, jnk and erk1/2 in vitro, and its phosphorylation levels positively correlate with twist1 protein levels in hek293 and breast cancer cells.	SIGNOR-173401
P28482	P42702	1	phosphorylation	down-regulates	0.369	Indeed, phosphorylation of the cytoplasmic domain of the low-affinity lif receptor alpha-subunit (lifr) in mono q-fractionated, lif-stimulated 3t3-l1 extracts occurred only in those fractions containing activated mapk;ser-1044 served as the major phosphorylation site in the human lifr for mapk both in agonist-stimulated 3t3-l1 lysates and by recombinant extracellular signal-regulated kinase 2 in vitro	SIGNOR-32753
P68036	P46934	1	ubiquitination	up-regulates activity	0.544	Only UbcH5 and Related Class I E2s Support Ubiquitination of S5a—UbcH5 belongs to the Class I family of E2s which contains a catalytic core (UBC domain) without a distinct Ub binding domain (38). To test whether other Class I E2s can also support ubiquitination of S5a, we assayed the ubiquitination of S5a with UbcH7 and the E3s, Nedd4, or Parkin. With either of these E3s, UbcH7 supported ubiquitination of S5a (Fig. 8, A and B). In addition, another Class I E2, Ubc4, a close homolog of UbcH5, supported ubiquitination of S5a by the APC, a multimeric Ring finger E3 responsible for cell cycle progression through mitosis (39) (Fig. 8C). Thus, multiple Class I E2s can support ubiquitination of S5a by various types of E3s (Table 1).	SIGNOR-272735
P08047	P14210	1	transcriptional regulation	up-regulates quantity by expression	0.2	Furthermore, in transient cotransfection assays, overexpression of Sp1 and/or Sp3 stimulated HGF promoter activity independently and additively through binding to the Sp1 binding site in the HGF gene promoter region.	SIGNOR-251739
O15550	P31268	1	transcriptional regulation	up-regulates quantity by expression	0.275	Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.	SIGNOR-260024
Q00839	P01375	1	post transcriptional regulation	up-regulates quantity by stabilization	0.2	In the present study, we show that hnRNP-U specifically enhances the expression of tumor necrosis factor alpha mRNA by increasing its stability, possibly through binding to the 3' untranslated region. We also show that hnRNP-U enhances the expression of several other genes as well, including GADD45A, HEXIM1, HOXA2, IER3, NHLH2, and ZFY, by binding to and stabilizing these mRNAs.	SIGNOR-262281
Q70E73	P00519	0	phosphorylation	up-regulates activity	0.284	Here we show that phosphorylation of Lpd by c-Abl increases its interaction with Ena/VASP proteins. This analysis revealed that, in vitro, four Lpd peptides harboring tyrosines (Y426, Y456, Y513, Y1226) are highly phosphorylated, and eight additional peptides are phosphorylated to a lesser extent (Figure 1C).	SIGNOR-262606
P40763	P08631	0	phosphorylation	up-regulates activity	0.618	Activation of STAT3 by the Src family kinase Hck requires a functional SH3 domain. Direct Phosphorylation of STAT3 on Tyr-705 by Src Family Kinases	SIGNOR-251267
P42574	P08590	1	cleavage	down-regulates quantity by destabilization	0.377	By sequencing and site-directed mutagenesis, a noncanonical cleavage site for caspase-3 was mapped to the C-terminal DFVE(135)G motif. We demonstrated that vMLC1 cleavage in failing myocardium in vivo is associated with a morphological disruption of the organized vMLC1 staining of sarcomeres, and with a reduction in myocyte contractile performance.	SIGNOR-270593
Q13153	P53350	1	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
P28482	P62136	0	dephosphorylation	down-regulates	0.446	P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3)	SIGNOR-103152
O95863	Q16512	0	phosphorylation	up-regulates	0.2	Pak1 phosphorylation of snail, a master regulator of epithelial-to-mesenchyme transition, modulates snail's subcellular localization and functionswe found for the first time that pak1 promotes transcription repression activity of snail from e-cadherin, occludin, and aromatase promoters. Pak1 regulates the repressor activity of snail by phosphorylating on ser(246). Pak1 phosphorylation of snail supports snail's accumulation in the nucleus as well as its repressor functions.	SIGNOR-135609
P06493	Q9BQQ3	1	phosphorylation	down-regulates activity	0.715	Here we show that GRASP65 is phosphorylated on serine 277 in interphase cells, and this is strongly enhanced in response to the addition of serum or epidermal growth factor. This is directly mediated by ERK suggesting that GRASP65 has some role in growth factor signal transduction. Phosphorylation of Ser-277 is also dramatically increased during mitosis, however this is mediated by Cdk1 and not by ERK. These results argue against Ser-277 phosphorylation alone causing the dissolution of GRASP65 oligomers and cisternal unstacking, although it may make a significant contribution to these events.	SIGNOR-262840
P28482	P19484	1	phosphorylation	down-regulates activity	0.413	Evidence for ERK2-mediated TFEB phosphorylation came from ERK2-TFEB coimmuno-precipitation (fig. S12C) in normal but not in starved medium and from a peptide-based kinase assay showing that mutation of Ser142 to alanine abolished ERK2-mediated phosphorylation (	SIGNOR-248279
P17509	P69905	1	transcriptional regulation	down-regulates quantity by repression	0.2	HOXB6 protein represses globin transcript levels in stably transfected K562 cells in a DNA-binding dependent fashion.	SIGNOR-261637
O43586	P00519	0	phosphorylation	up-regulates activity	0.597	PSTPIP1 was phosphorylated by c-Abl. Tyr-344 is a major c-Abl phosphorylation site.PSTPIP1 was able to bridge c-Abl to the PEST-type PTPs.	SIGNOR-251431
Q9UI47	Q06413	0	transcriptional regulation	up-regulates quantity by expression	0.241	GATA-4 and MEF2C are known to bind to the GATA box 2 in the major promoter of CTNNA3 and this element is essential in directly regulating expression of CTNNA3 in cardiac muscle cells. The co-transfection of GATA-4 with MEF2C leads to a synergistic activation of the CTNNA3 promoter	SIGNOR-265491
O15297	O60341	1	dephosphorylation	down-regulates activity	0.465	We demonstrated here that phosphorylation and dephosphorylation of LSD1 at S131 and S137 was mediated by casein kinase 2 (CK2) and wild-type p53-induced phosphatase 1 (WIP1), respectively. LSD1, RNF168 and 53BP1 interacted with each other directly. CK2-mediated phosphorylation of LSD1 exhibited no impact on its interaction with 53BP1, but promoted its interaction with RNF168 and RNF168-dependent 53BP1 ubiquitination and subsequent recruitment to the DNA damage sites.	SIGNOR-276905
P10586	P31749	1	dephosphorylation	down-regulates	0.342	Knock-down of lar by the l3 sirna probe markedly inhibited the insulin-stimulated increase in the phosphorylation of protein kinase b (pkb, also called akt) on serine 473 by >90%	SIGNOR-137246
O00141	Q9HC98	0	phosphorylation	up-regulates activity	0.338	The present study is the first report of a protein kinase (NEK6) capable of phosphorylating the hydrophobic motif of SGK1, although our data suggest that NEK6 may not mediate this reaction in cells. Nevertheless, the phosphorylation of the hydrophobic motif of SGK1in vitro, coupled with the phosphorylation of the T-loop with PDK1, may be a useful way of generating fully active wild type SGK1. Ser377 and Ser422of SGK1, and the CDK7 T-loop peptide, which are phosphorylated by NEK6.	SIGNOR-250297
P04626	O95243	1	phosphorylation	up-regulates activity	0.2	Importantly, we found that overexpression of HER2 alone is sufficient to induce MED1 phosphorylation at Thr (1032), a key site that is known to be critical for its functions, whereas blockage of HER2 or its downstream MAP kinase diminishes its phosphor ylation levels in these cells.	SIGNOR-279408
P14618	Q00534	0	phosphorylation	down-regulates activity	0.259	Here, using human cancer cells and patient-derived xenografts in mice, we show that the cyclin D3-CDK6 kinase phosphorylates and inhibits the catalytic activity of two key enzymes in the glycolytic pathway, 6-phosphofructokinase and pyruvate kinase M2.	SIGNOR-279158
Q7KZI7	Q7L7X3	0	phosphorylation	up-regulates activity	0.414	MARK family kinases can be activated by phosphorylation of a conserved threonine (Thr-208 in MARK2), and inactivated by phosphorylation of a serine (Ser-212), both in the activation loop of the catalytic domain. Activation is achieved by the kinases MARKK/TAO1 or LKB1, although the inactivating kinase was unknown. We show here that GSK3beta serves the role of the inhibitory kinase.	SIGNOR-276164
P13727	P11678	0	post translational modification	up-regulates activity	0.434	Human eosinophils are bone marrow-derived, non-dividing granulocytes of the innate immune system, which store the highly cationic proteins eosinophil peroxidase (EPO), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP) in secondary granules. we demonstrated that Tyr nitration of the eosinophil granule proteins is exclusively mediated by EPO, in the presence of functional NADPH oxidase and minute amounts of NOx. EPO appears to nitrate itself via an autocatalytic mechanism.	SIGNOR-261703
P12931	P46934-4	1	phosphorylation	up-regulates activity	0.417	Activation of c-Src by epidermal growth factor (EGF) also promoted tyrosine phosphorylation and enhanced the activity of NEDD4.	SIGNOR-276860
Q8N726	O15119	0	transcriptional regulation	down-regulates quantity by repression	0.395	TBX2 and TBX3 function as transcriptional repressors and both have been shown to inhibit myogenesis (Carlson et al, 2002; Zhu et al, 2014). Abnormal expression of TBX2 has been reported in several cancers including breast, pancreas, and melanoma, where it has been shown to drive proliferation (reviewed in Abrahams et al (2010)). As has been previously shown in other cell types, TBX2 was found to induce a downregulation of p14/19ARF and function as a direct repressor of p21 in RMS	SIGNOR-249603
P31751	P30405	1	phosphorylation	up-regulates activity	0.2	In turn, mitochondrial Akt2 phosphorylates Ser31 in cyclophilin D (CypD), a regulator of organelle functions. Akt2-phosphorylated CypD supports mitochondrial bioenergetics and opposes tumor cell death, conferring resistance to PI3K therapy.	SIGNOR-276875
O15111	P24385	1	phosphorylation	down-regulates	0.379	Ikkalpha regulates subcellular localization and proteolysis of cyclin d1 by phosphorylation of cyclin d1 at thr286.	SIGNOR-139570
P27361	P51452	0	dephosphorylation	down-regulates activity	0.665	The activation of the mapk activity requires the dual phosphorylation of the ser/thr and tyr residues in the txy kinase activation motif (1113), and deactivation occurs through the action of either ser/thr protein phosphatase (14), protein-tyrosine phosphatase (ptp) (14, 15), or dual specificity phosphatases	SIGNOR-103035
Q08881	P19174	1	phosphorylation	up-regulates	0.637	In t cells, the predominant tec kinase is itk, which functions downstream of the t-cell receptor to regulate phospholipase c-gamma.	SIGNOR-165803
Q9H0M0	P36897	1	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
P14921	Q9UQM7	0	phosphorylation	down-regulates	0.309	Treatment of ets1 by t-cell nuclear extract or phosphorylation of these four serines by calmodulin-dependent kinase ii (camk ii) has recently been reported to decrease ets1 dna binding by reinforcing autoinhibition	SIGNOR-96334
P19235	Q9Y314	0	ubiquitination	up-regulates activity	0.331	Erythropoietin receptors associate with a ubiquitin ligase, p33RUL, and require its activity for erythropoietin-induced proliferation. This receptor-associated ubiquitin ligase, RUL, co-precipitated with EpoR from mammalian cells and mediated ubiquitination of EpoR. RUL mediates EpoR ubiquitination in COS7 cells and is inducibly ubiquitinated after Epo treatment. This observation is consistent with the lack of effects on EpoR stability by RUL-mediated ubiquitination in COS7 cells (Fig. 4).	SIGNOR-271477
P17612	P11831	1	phosphorylation	up-regulates	0.256	Myotonic dystrophy protein kinase (DMPK), a muscle- and neuron-restricted kinase, enhanced SRF-mediated promoter activity of the skeletal and cardiac alpha-actin genes in C2C12 myoblasts as well as in nonmyogenic cells. \| Threonine 159 in the MADS box alphaI coil was a specific phosphorylation target in vitro as well as in vivo of both DMPK and protein kinase C-alpha.	SIGNOR-188177
P18847	Q99612	0	transcriptional regulation	up-regulates quantity by expression	0.394	KLF6 binds directly to and activates the ATF3 promoter.	SIGNOR-266051
P38936	Q9Y463	0	phosphorylation	up-regulates activity	0.258	Mirk exerts its anti-apoptotic effects during muscle differentiation at least in part through effects on the cell cycle inhibitor and pro-survival molecule p21cip1. Overexpression and rna interference experiments demonstrated that mirk phosphorylates p21 within its nuclear localization domain at ser-153 causing a portion of the typically nuclear p21 to localize in the cytoplasm.Translocation to the cytoplasm enables p21 to block apoptosis through inhibitory interaction with pro-apoptotic molecules.	SIGNOR-235635
O14578	P24844	1	phosphorylation	up-regulates activity	0.561	Activation of the catalytic ATPase domain residing in the N‐terminus of the heavy chain relies on the reversible phosphorylation of the associated MLC on Ser19 (monophosphorylation), or in some cases on both Thr18 and Ser19 (diphosphorylation)\|We detected Ser19 of MLC as the common phosphorylation site for the catalytic domains of MRCK_/_, ROK_, MLCK and PAK_, but only ROK_ and CRIK are able to phosphorylate both Thr18 and Ser19 residues causing diphosphorylation.	SIGNOR-260306
P54132	Q13315	0	phosphorylation	up-regulates	0.775	Mitotic phosphorylation of blm was partially dependent on atm, and phosphorylation sites on blm were identified. A phosphospecific antibody against one of these sites (thr-99) revealed radiation-induced phosphorylation, which was defective in ataxia-telangiectasia cells. These data suggest that atm and blm function together in recognizing abnormal dna structures by direct interaction and that these phosphorylation sites in blm are important for radiosensitivity status but not for sce frequency.	SIGNOR-88010
Q9UBC3	P42658	1	transcriptional regulation	down-regulates quantity by repression	0.327	Dnmt3b was responsible for transcriptional silencing of Dpp6 gene as depletion of Dnmt3b resulted in increased mRNA and protein expression of Dpp6.	SIGNOR-268963
P31350	P06493	0	phosphorylation	down-regulates	0.504	We found that, during g2, following cdk-mediated phosphorylation of thr33, rrm2 is degraded via scf(cyclin f) to maintain balanced dntp pools and genome stability.	SIGNOR-197630
Q9BW19	P06493	0	phosphorylation	up-regulates quantity by stabilization	0.458	We confirmed that CDK1 phosphorylates Ser6 (Supplementary Fig S5B) and demonstrated that KIFC1 displays CDK1-mediated resistance to ubiquitination by the APC/C (Fig S5C).	SIGNOR-277294
Q13362-1	Q13315	0	phosphorylation	up-regulates activity	0.378	In the present study, we demonstrate that ataxia-telangiectasia mutated (ATM) directly phosphorylates and specifically regulates B56γ3, B56γ2 and B56δ, after DNA damage. We further show that phosphorylation of B56γ3 at Ser510 leads to an increase in B56γ3-PP2A complexes, and direction of PP2A phosphatase activity toward the substrate p53, activating its tumor-suppressive functions. we show that Ser510 phosphorylation significantly enhances the ability of B56γ3 to inhibit cell proliferation and anchorage-independent growth.	SIGNOR-276318
P03372	Q13153	0	phosphorylation	up-regulates	0.534	Pak1 directly phosphorylated the activation function-2 domain of the er at the n-terminal residue ser305, and its mutation to ala (s305a) abolished the pak1-mediated phosphorylation and transactivation functions of the er	SIGNOR-94206
P06493	Q9UKX7	1	phosphorylation	down-regulates	0.421	These results suggest that both ERK and Cdk1 directly phosphorylate Nup50 at Ser221 in intact cells\|Notably, erk phosphorylation of the fg repeat region of nup50 reduced its affinity for importin-beta family proteins, importin-beta and transportin.	SIGNOR-188061
P28482	P17302	1	phosphorylation	down-regulates activity	0.608	These studies confirm that connexin-43 is a MAP kinase substrate in vivo and that phosphorylation on Ser255, Ser279, and/or Ser282 initiates the down-regulation of gap junctional communication. Studies with connexin-43 mutants suggest that MAP kinase phosphorylation at one or more of the tandem Ser279/Ser282 sites is sufficient to disrupt gap junctional intercellular communication.	SIGNOR-249401
Q9H9S0	Q05397	0	phosphorylation	up-regulates activity	0.274	In addition, FAK directly phosphorylates Nanog in a dose-dependent manner by in vitro kinase assay and in cancer cells in vivo. The site-directed mutagenesis of Nanog tyrosines, Y35F and Y174F, blocked phosphorylation and binding by FAK.	SIGNOR-276410
P21730	Q05655	0	phosphorylation	down-regulates	0.2	Whole cell phosphorylation assays with specific inhibitors as well as in vitro phosphorylation assays with recombinant enzymes and peptide substrates revealed that phosphorylation of ser-334 is regulated by protein kinase c-beta this study is among the first to analyze in a detailed manner, using a non-mutational approach, modifications of a defined phosphorylation site in a g protein-coupled receptor and to correlate these findings with functional parameters of receptor deactivation.	SIGNOR-73967
Q9Y2J4	Q9H0M0	0	ubiquitination	up-regulates activity	0.29	AMOTL2 mono-ubiquitination by WWP1 promotes contact inhibition by facilitating LATS activation\|Here, we provide evidence that the E3 ligase WWP1 (WW-domain containing protein 1) mono-ubiquitinates AMOTL2 (angiomotin-like 2) at K347 and K408.	SIGNOR-271873
P59595	P53539	1	transcriptional regulation	up-regulates quantity by expression	0.2	The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well	SIGNOR-260728
O60285	Q96QC0	1	phosphorylation	up-regulates activity	0.2	Here, we show that NUAK1 is a predominantly nuclear protein that associates with a network of nuclear protein phosphatase 1 (PP1) interactors and that PNUTS, a nuclear regulatory subunit of PP1, is phosphorylated by NUAK1.\|Inhibition of NUAK1 abolishes chromatin association of PNUTS, reduces spliceosome activity, and suppresses nascent RNA synthesis.	SIGNOR-280051
P53350	Q9UBB4	1	phosphorylation	down-regulates	0.353	Phosphorylation of ataxin-10 by polo-like kinase 1 is required for cytokinesis. Plk1 phosphorylates ataxin-10 at s77 and t82 in vitro. we found that ataxin-10 is ubiquitinated, and is subject to proteasome-dependent degradation, which is delayed in the 2a mutant. We propose a model in which plk1 phosphorylation of ataxin-10 influences its degradation and cytokinesis	SIGNOR-176122
Q07666	P06213	0	phosphorylation	up-regulates activity	0.363	Thus, Tyr phosphorylation of Sam68 by IR could modulate its association with the splicing machinery in a similar way to that described for p59 fyn, and this way, it could influence splice site selection.	SIGNOR-278946
P41229	P68431	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-264305
Q13547	O95471	1	transcriptional regulation	down-regulates quantity by repression	0.2	ChIP assays revealed that SNAI1P is recruited on the CLDN7 gene promoter along with the co-repressor CtBP1 and the effector HDAC1.\|These data further suggest that HDAC1 is involved in the SNAI1P-mediated repression of the human CLDN7 gene promoter.	SIGNOR-254106
O43638	P98177	1	transcriptional regulation	down-regulates quantity by repression	0.2	Fkhl18 suppressed the transcriptional activity of FoxO3a and FoxO4.	SIGNOR-261611
Q8IUH4	Q01726	1	palmitoylation	up-regulates activity	0.274	Collectively these results suggest that ZDHHC13 phosphorylation by ATR following UVB irradiation promotes its interaction with MC1R to stimulate MC1R palmitoylation.Activating MC1R palmitoylation rescues the defect of MC1R RHC variants	SIGNOR-273518
Q86WB0	P24941	0	phosphorylation	down-regulates	0.2	Moreover, we found cyclin b1/cdk1 to phosphorylate nipa at ser-395 in mitosis. Mutation of both ser-359 and ser-395 impaired effective inactivation of the scfnipa complex, resulting in reduced levels of mitotic cyclin b1	SIGNOR-154051
P45985	Q99683	0	phosphorylation	up-regulates activity	0.631	A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subs of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase)	SIGNOR-45373
P19419	Q16539	0	phosphorylation	up-regulates	0.526	We demonstrate here that elk-1 is barely activated by a third subclass of map kinases (p38), most likely because the critical residues ser383 and ser389 are poorly phosphorylated by p38 map kinase.	SIGNOR-47630
P05771	P28329	1	phosphorylation	up-regulates	0.286	Protein kinase c isoforms differentially phosphorylate human choline acetyltransferase regulating its catalytic activity.	SIGNOR-129288
Q99814	Q9Y4C1	1	transcriptional regulation	up-regulates quantity by expression	0.265	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-271583

Q01105-2

P68400

0

phosphorylation

down-regulates

0.365

Ckii-mediated phosphorylation at ser9 hinders nuclear import of set

SIGNOR-200798

O00141

Q6A1A2

0

phosphorylation

up-regulates

0.2

Our results are consistent with a model in which activation of sgk by igf-1 or hydrogen peroxide is initiated by a ptdins(3,4, 5)p3-dependent activation of pdk2, which phosphorylates ser422.

SIGNOR-66234

Q5T447

Q14790

1

polyubiquitination

down-regulates activity

0.336

HECTD3, a new E3 ubiquitin ligase, interacts with caspase-8 death effector domains and ubiquitinates caspase-8 with K63-linked polyubiquitin chains that do not target caspase-8 for degradation but decrease the caspase-8 activation. HECTD3 ubiquitinates caspase-8 with K63-linked polyubiquitin chains at K215.

SIGNOR-272077

P04629

A7KAX9

1

relocalization

up-regulates

0.602

Grit translocation was regulated by receptor stimulation

SIGNOR-95809

Q05655

P49715

1

phosphorylation

down-regulates quantity by destabilization

0.2

We next demonstrated by immunoprecipitation that IL-32\u03b2 interacted with PKC\u03b4 and C/EBP\u03b1, thereby mediating C/EBP\u03b1 Ser-21 phosphorylation by PKC\u03b4.

SIGNOR-279427

Q6ZVD8

P31751

1

dephosphorylation

down-regulates activity

0.604

The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells.

SIGNOR-248729

Q9UGP8

P67870

0

phosphorylation

up-regulates activity

0.2

Sec63 was identified as a novel substrate and binding partner of protein kinase CK2. We identified serine 574, serine 576 and serine 748 as CK2 phosphorylation sites. Phosphorylation of Sec63 by CK2 enhanced its binding to Sec62.

SIGNOR-265270

O75592

O75385

1

ubiquitination

down-regulates quantity

0.284

Cell-based results demonstrate that the human PHR protein PAM restricts ULK1 protein levels (Fig.\u00a05h, i), and is sufficient to ubiquitinate ULK1 in a proteasome-dependent manner (Fig.\u00a05j).|Human PAM ubiquitinates ULK1 and regulates ULK1 levels.

SIGNOR-278765

Q9BYB0

O14490

0

relocalization

up-regulates activity

0.2

SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).

SIGNOR-264588

Q9BY84

P28482

0

phosphorylation

up-regulates quantity by stabilization

0.808

Phosphorylation of Ser-446 determines stability of MKP-7.|We also determined that MKP-7 phosphorylated at Ser-446 has a longer half-life than unphosphorylated form of the wild type protein, as does a phospho-mimic mutant of MKP-7. These results indicate that activation of the ERK pathway strongly blocks JNK activation through stabilization of MKP-7 mediated by phosphorylation.

SIGNOR-249389

P14598

P17252

0

phosphorylation

up-regulates

0.553

Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation.

SIGNOR-89178

Q16539

P06400

1

phosphorylation

down-regulates

0.539

P38 bypasses the cell cycle-associated hierarchical phosphorylation and directly phosphorylates rb on ser567, which is not phosphorylated during the normal cell cycle. Phosphorylation by p38, but not cdks, triggers an interaction between rb and the human homolog of murine double minute 2 (hdm2), leading to degradation of rb, release of e2f1 and cell death.

SIGNOR-168178

O43683

O43684

1

relocalization

up-regulates activity

0.943

Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity

SIGNOR-252019

P17252

O15511

1

phosphorylation

up-regulates activity

0.2

PKC\u03b1 phosphorylates and activates ARPC5, which organizes the actin net dorsolateral of nucleus.

SIGNOR-280078

P24666

P29317

1

dephosphorylation

down-regulates activity

0.66

The SAM domain tyrosine Y960 which has been implicated in downstream PI3K signaling is dephosphorylated exclusively by HCPTP-B. The activation loop tyrosine (Y772) which directly controls kinase activity is dephosphorylated about six times faster by HCPTP-A. In contrast, the juxtamembrane tyrosines (Y575, Y588 and Y594) which are implicated in both control of kinase activity and downstream signaling are dephosphorylated by both variants with similar rates

SIGNOR-246023

P17931

P48729

0

phosphorylation

up-regulates

0.308

These results indicate that phosphorylation of gal-3 promotes its nuclear export after apoptotic stimuli through enhanced nuclear export.

SIGNOR-124583

Q15691

P12931

0

phosphorylation

down-regulates activity

0.2

These data suggest that Src phosphorylates endogenous EB1 at Y247.

SIGNOR-278215

Q9BR76

Q6UB99

0

transcriptional regulation

up-regulates quantity by expression

0.2

Neurite growth-related genes such as Trkb, Bdnf, Gap43, Coronin 1B, and Rab13 are downregulated in ANKRD11-deficient neurons.

SIGNOR-266737

Q9UHV7

P49336

0

phosphorylation

down-regulates quantity by destabilization

0.901

Here, cyclin C-Cdk8 phosphorylation of Med13 most likely primes the phosphodegron for destruction.

SIGNOR-279687

P07948

Q04760

1

phosphorylation

up-regulates activity

0.2

We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).

SIGNOR-276186

Q13153

P29320

0

phosphorylation

up-regulates activity

0.277

Etk kinase directly phosphorylates and activates PAK1 in response to estrogen.|We demonstrated that estrogen-activated Etk directly phosphorylated PAK1 on Tyr153.

SIGNOR-278398

Q12834

Q96GD4

0

phosphorylation

down-regulates activity

0.767

When SAC is active, Aurora kinase B (AurkB) phosphorylates and inactivates CDC20, to prevent the activation of anaphase promoting complex and cyclosome (APC/C).|When SAC is active, Aurora kinase B (AurkB) phosphorylates and inactivates CDC20, to prevent the activation of anaphase-promoting complex/cyclosome (APC/C) (Hagting et al., xref ; Nasmyth, xref ; Ruchaud et al., xref ).

SIGNOR-280190

Q9NYV6

Q13131

0

phosphorylation

down-regulates

0.2

We show that ampk down-regulates rrna synthesis under glucose restriction by phosphorylating the rna polymerase i (pol i)-associated transcription factor tif-ia at a single serine residue (ser-635).

SIGNOR-188403

Q13418

Q96C90

1

phosphorylation

up-regulates activity

0.398

We conclude that ILK may activate smooth-muscle contraction both directly, via phosphorylation of myosin, and indirectly, via phosphorylation and activation of CPI-17 and PHI-1, leading to inhibition of MLCP.|CPI-17 and PHI-1 thiophosphorylated by ILK at Thr(38) or Thr(57) respectively inhibited myosin light-chain phosphatase (MLCP) activity bound to myosin

SIGNOR-265741

P16333

P07766

0

relocalization

up-regulates activity

0.372

We present strong evidence that ligand engagement of TCR-CD3 induces a conformational change that exposes a proline-rich sequence in CD3ϵ and results in recruitment of the adaptor protein Nck.

SIGNOR-259934

P51608

Q06413

1

transcriptional regulation

down-regulates quantity by repression

0.346

MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1.

SIGNOR-264680

P68400

O75676

1

phosphorylation

up-regulates activity

0.281

Here we report that the CK2 protein kinase, which contributes to NF-kappaB activation following UV radiation in a p38-dependent manner, physically interacts with MSK2 but not MSK1 and that CK2 inhibition specifically impairs UV-induced MSK2 kinase activation. A putative site of CK2 phosphorylation was mapped to MSK2 residue Ser(324) and when substituted to alanine (S324A) also compromised MSK2 activity.Serine 324 is required for UV-induced MSK2 activation and for autophosphorylation at MSK2-Ser196.

SIGNOR-276268

P04626

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.627

The ErbB2 kinase domain is required for GA-induced and CHIP-dependent ErbB2 ubiquitination and degradation .

SIGNOR-278645

Q9GZQ8

Q8TD19

0

phosphorylation

down-regulates activity

0.2

LC3B is phosphorylated at Thr-50 within the LDS by serine/threonine kinase (STK) 3 and STK4. Here, we identified LIR motifs in STK3 and atypical protein kinase Cζ (PKCζ) and never in mitosis A (NIMA)-related kinase 9 (NEK9). All three kinases phosphorylated LC3B Thr-50 in vitro A phospho-mimicking substitution of Thr-50 impaired binding of several LIR-containing proteins, such as ATG4B, FYVE, and coiled-coil domain-containing 1 (FYCO1), and autophagy cargo receptors p62/sequestosome 1 (SQSTM1) and neighbor of BRCA1 gene (NBR1).

SIGNOR-273904

Q9NQU5

P48431

1

phosphorylation

up-regulates quantity

0.2

PAK5 promotes the cell stemness ability by phosphorylating SOX2 in lung squamous cell carcinomas.|The absence of PAK5 abolishes self-renewal ability of LUSC cells by decreasing the expression and phosphorylation of SOX2 in vitro and in vivo.

SIGNOR-280060

Q92911

Q06710

0

transcriptional regulation

up-regulates quantity by expression

0.408

Pax8 has an essential role in thyroid organogenesis and differentiation, being the main mediator of thyroid gene transcription, including the NIS gene.

SIGNOR-251990

P42345

Q13322

1

phosphorylation

up-regulates

0.412

The adaptor protein grb10 was identified as an mtorc1 substrate that mediates the phosphoinositide 3-kinase.

SIGNOR-174071

Q8TAS1

P16949

1

phosphorylation

down-regulates

0.51

This promigratory phenotype resulted from increased stathmin protein levels, caused by a lack of kis-mediated stathmin phosphorylation at serine 38 and diminished stathmin protein degradation.

SIGNOR-182489

P15172

Q13683

1

transcriptional regulation

up-regulates quantity by expression

0.286

Only myogenin and MyoD were able to efficiently trans-activate the alpha7 promoter-CAT construct (Fig. 7). Myogenin trans-activated the promoter by _2-fold whereas MyoD was able to trans-activate by nearly 4-fold, indicating that both of these factors may play a role in alpha7 gene expression during muscle development.

SIGNOR-241518

P17252

P31431

1

phosphorylation

up-regulates activity

0.732

The phosphorylation state of Ser(183) in the cytoplasmic tail of syndecan-4 determines the binding affinity of the cytoplasmic tail to phosphatidylinositol 4,5-bisphosphate (PIP(2)), the capacity of the tail to multimerize, and its ability to activate protein kinase C (PKC) alpha. We sought to identify the kinase responsible for this phosphorylation and to determine its downstream effects on PKCalpha activity and on endothelial cell function. Among several PKC isoenzymes tested, only PKCalpha and -delta were able to specifically phosphorylate Ser(183) in vitro. However, studies in cultured endothelial cells showed that the phosphorylation level of syndecan-4 was significantly reduced in endothelial cells expressing a dominant negative (DN) PKCdelta but not a DN PKCalpha mutant.

SIGNOR-249149

Q9Y2H1

P14373

0

ubiquitination

up-regulates activity

0.2

TRIM27 catalyzes non-degradative K6- and K11-linked ubiquitination of the serine/threonine kinase 38-like (STK38L) kinase. In turn, STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination of ULK1

SIGNOR-270347

P01584

Q16665

0

transcriptional regulation

up-regulates quantity by expression

0.336

We finally confirmed that in the absence of HIF-1α there was a significant reduction at the protein level in pro-caspase-1, activated caspase-1, pro-IL-1β, and ultimately active IL-1β (Fig. 4g and h). These data show that adenosine induced up-regulation of IL-1β is dependent on a CREB/HIF-1α pathway which is distinct from the NF-kB pathway used for initial production of IL-1β in response to LPS.

SIGNOR-251718

P28562

Q13950

1

dephosphorylation

up-regulates activity

0.353

In a separate study, MKP-1 was shown to induce osteogenesis by dephosphorylating Ser125 on Runx2 isoform type II (37).|MKP-1 increases RUNX2 activity and downregulates MAPK, cyclin D1 in differentiated osteoblasts inducing growth arrest and mineralization.

SIGNOR-277143

P24941

Q5TZA2

1

phosphorylation

down-regulates

0.2

Finally, phosphorylation of tax1bp2 at serine-763 by cyclin-dependent kinase (cdk)2 abolished the tax1bp2-mediated p38 activation and tumor-suppressive activity, indicating that tax1bp2 can adapt cdk2 signaling to the p38/p53/p21 pathway.

SIGNOR-197593

P28482

Q15672

1

phosphorylation

up-regulates

0.304

We identified the serine 68 (s68) as a major phosphorylation site of twist1 by mass spectrometry and with specific antibodies. This s68 is phosphorylated by p38, jnk and erk1/2 in vitro, and its phosphorylation levels positively correlate with twist1 protein levels in hek293 and breast cancer cells.

SIGNOR-173401

P28482

P42702

1

phosphorylation

down-regulates

0.369

Indeed, phosphorylation of the cytoplasmic domain of the low-affinity lif receptor alpha-subunit (lifr) in mono q-fractionated, lif-stimulated 3t3-l1 extracts occurred only in those fractions containing activated mapk;ser-1044 served as the major phosphorylation site in the human lifr for mapk both in agonist-stimulated 3t3-l1 lysates and by recombinant extracellular signal-regulated kinase 2 in vitro

SIGNOR-32753

P68036

P46934

1

ubiquitination

up-regulates activity

0.544

Only UbcH5 and Related Class I E2s Support Ubiquitination of S5a—UbcH5 belongs to the Class I family of E2s which contains a catalytic core (UBC domain) without a distinct Ub binding domain (38). To test whether other Class I E2s can also support ubiquitination of S5a, we assayed the ubiquitination of S5a with UbcH7 and the E3s, Nedd4, or Parkin. With either of these E3s, UbcH7 supported ubiquitination of S5a (Fig. 8, A and B). In addition, another Class I E2, Ubc4, a close homolog of UbcH5, supported ubiquitination of S5a by the APC, a multimeric Ring finger E3 responsible for cell cycle progression through mitosis (39) (Fig. 8C). Thus, multiple Class I E2s can support ubiquitination of S5a by various types of E3s (Table 1).

SIGNOR-272735

P08047

P14210

1

transcriptional regulation

up-regulates quantity by expression

0.2

Furthermore, in transient cotransfection assays, overexpression of Sp1 and/or Sp3 stimulated HGF promoter activity independently and additively through binding to the Sp1 binding site in the HGF gene promoter region.

SIGNOR-251739

O15550

P31268

1

transcriptional regulation

up-regulates quantity by expression

0.275

Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.

SIGNOR-260024

Q00839

P01375

1

post transcriptional regulation

up-regulates quantity by stabilization

0.2

In the present study, we show that hnRNP-U specifically enhances the expression of tumor necrosis factor alpha mRNA by increasing its stability, possibly through binding to the 3' untranslated region. We also show that hnRNP-U enhances the expression of several other genes as well, including GADD45A, HEXIM1, HOXA2, IER3, NHLH2, and ZFY, by binding to and stabilizing these mRNAs.

SIGNOR-262281

Q70E73

P00519

0

phosphorylation

up-regulates activity

0.284

Here we show that phosphorylation of Lpd by c-Abl increases its interaction with Ena/VASP proteins. This analysis revealed that, in vitro, four Lpd peptides harboring tyrosines (Y426, Y456, Y513, Y1226) are highly phosphorylated, and eight additional peptides are phosphorylated to a lesser extent (Figure 1C).

SIGNOR-262606

P40763

P08631

0

phosphorylation

up-regulates activity

0.618

Activation of STAT3 by the Src family kinase Hck requires a functional SH3 domain. Direct Phosphorylation of STAT3 on Tyr-705 by Src Family Kinases

SIGNOR-251267

P42574

P08590

1

cleavage

down-regulates quantity by destabilization

0.377

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

SIGNOR-270593

Q13153

P53350

1

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

P28482

P62136

0

dephosphorylation

down-regulates

0.446

P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3)

SIGNOR-103152

O95863

Q16512

0

phosphorylation

up-regulates

0.2

Pak1 phosphorylation of snail, a master regulator of epithelial-to-mesenchyme transition, modulates snail's subcellular localization and functionswe found for the first time that pak1 promotes transcription repression activity of snail from e-cadherin, occludin, and aromatase promoters. Pak1 regulates the repressor activity of snail by phosphorylating on ser(246). Pak1 phosphorylation of snail supports snail's accumulation in the nucleus as well as its repressor functions.

SIGNOR-135609

P06493

Q9BQQ3

1

phosphorylation

down-regulates activity

0.715

Here we show that GRASP65 is phosphorylated on serine 277 in interphase cells, and this is strongly enhanced in response to the addition of serum or epidermal growth factor. This is directly mediated by ERK suggesting that GRASP65 has some role in growth factor signal transduction. Phosphorylation of Ser-277 is also dramatically increased during mitosis, however this is mediated by Cdk1 and not by ERK. These results argue against Ser-277 phosphorylation alone causing the dissolution of GRASP65 oligomers and cisternal unstacking, although it may make a significant contribution to these events.

SIGNOR-262840

P28482

P19484

1

phosphorylation

down-regulates activity

0.413

Evidence for ERK2-mediated TFEB phosphorylation came from ERK2-TFEB coimmuno-precipitation (fig. S12C) in normal but not in starved medium and from a peptide-based kinase assay showing that mutation of Ser142 to alanine abolished ERK2-mediated phosphorylation (

SIGNOR-248279

P17509

P69905

1

transcriptional regulation

down-regulates quantity by repression

0.2

HOXB6 protein represses globin transcript levels in stably transfected K562 cells in a DNA-binding dependent fashion.

SIGNOR-261637

O43586

P00519

0

phosphorylation

up-regulates activity

0.597

PSTPIP1 was phosphorylated by c-Abl. Tyr-344 is a major c-Abl phosphorylation site.PSTPIP1 was able to bridge c-Abl to the PEST-type PTPs.

SIGNOR-251431

Q9UI47

Q06413

0

transcriptional regulation

up-regulates quantity by expression

0.241

GATA-4 and MEF2C are known to bind to the GATA box 2 in the major promoter of CTNNA3 and this element is essential in directly regulating expression of CTNNA3 in cardiac muscle cells. The co-transfection of GATA-4 with MEF2C leads to a synergistic activation of the CTNNA3 promoter

SIGNOR-265491

O15297

O60341

1

dephosphorylation

down-regulates activity

0.465

We demonstrated here that phosphorylation and dephosphorylation of LSD1 at S131 and S137 was mediated by casein kinase 2 (CK2) and wild-type p53-induced phosphatase 1 (WIP1), respectively. LSD1, RNF168 and 53BP1 interacted with each other directly. CK2-mediated phosphorylation of LSD1 exhibited no impact on its interaction with 53BP1, but promoted its interaction with RNF168 and RNF168-dependent 53BP1 ubiquitination and subsequent recruitment to the DNA damage sites.

SIGNOR-276905

P10586

P31749

1

dephosphorylation

down-regulates

0.342

Knock-down of lar by the l3 sirna probe markedly inhibited the insulin-stimulated increase in the phosphorylation of protein kinase b (pkb, also called akt) on serine 473 by >90%

SIGNOR-137246

O00141

Q9HC98

0

phosphorylation

up-regulates activity

0.338

The present study is the first report of a protein kinase (NEK6) capable of phosphorylating the hydrophobic motif of SGK1, although our data suggest that NEK6 may not mediate this reaction in cells. Nevertheless, the phosphorylation of the hydrophobic motif of SGK1in vitro, coupled with the phosphorylation of the T-loop with PDK1, may be a useful way of generating fully active wild type SGK1. Ser377 and Ser422of SGK1, and the CDK7 T-loop peptide, which are phosphorylated by NEK6.

SIGNOR-250297

P04626

O95243

1

phosphorylation

up-regulates activity

0.2

Importantly, we found that overexpression of HER2 alone is sufficient to induce MED1 phosphorylation at Thr (1032), a key site that is known to be critical for its functions, whereas blockage of HER2 or its downstream MAP kinase diminishes its phosphor ylation levels in these cells.

SIGNOR-279408

P14618

Q00534

0

phosphorylation

down-regulates activity

0.259

Here, using human cancer cells and patient-derived xenografts in mice, we show that the cyclin D3-CDK6 kinase phosphorylates and inhibits the catalytic activity of two key enzymes in the glycolytic pathway, 6-phosphofructokinase and pyruvate kinase M2.

SIGNOR-279158

Q7KZI7

Q7L7X3

0

phosphorylation

up-regulates activity

0.414

MARK family kinases can be activated by phosphorylation of a conserved threonine (Thr-208 in MARK2), and inactivated by phosphorylation of a serine (Ser-212), both in the activation loop of the catalytic domain. Activation is achieved by the kinases MARKK/TAO1 or LKB1, although the inactivating kinase was unknown. We show here that GSK3beta serves the role of the inhibitory kinase.

SIGNOR-276164

P13727

P11678

0

post translational modification

up-regulates activity

0.434

Human eosinophils are bone marrow-derived, non-dividing granulocytes of the innate immune system, which store the highly cationic proteins eosinophil peroxidase (EPO), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP) in secondary granules. we demonstrated that Tyr nitration of the eosinophil granule proteins is exclusively mediated by EPO, in the presence of functional NADPH oxidase and minute amounts of NOx. EPO appears to nitrate itself via an autocatalytic mechanism.

SIGNOR-261703

P12931

P46934-4

1

phosphorylation

up-regulates activity

0.417

Activation of c-Src by epidermal growth factor (EGF) also promoted tyrosine phosphorylation and enhanced the activity of NEDD4.

SIGNOR-276860

Q8N726

O15119

0

transcriptional regulation

down-regulates quantity by repression

0.395

TBX2 and TBX3 function as transcriptional repressors and both have been shown to inhibit myogenesis (Carlson et al, 2002; Zhu et al, 2014). Abnormal expression of TBX2 has been reported in several cancers including breast, pancreas, and melanoma, where it has been shown to drive proliferation (reviewed in Abrahams et al (2010)). As has been previously shown in other cell types, TBX2 was found to induce a downregulation of p14/19ARF and function as a direct repressor of p21 in RMS

SIGNOR-249603

P31751

P30405

1

phosphorylation

up-regulates activity

0.2

In turn, mitochondrial Akt2 phosphorylates Ser31 in cyclophilin D (CypD), a regulator of organelle functions. Akt2-phosphorylated CypD supports mitochondrial bioenergetics and opposes tumor cell death, conferring resistance to PI3K therapy.

SIGNOR-276875

O15111

P24385

1

phosphorylation

down-regulates

0.379

Ikkalpha regulates subcellular localization and proteolysis of cyclin d1 by phosphorylation of cyclin d1 at thr286.

SIGNOR-139570

P27361

P51452

0

dephosphorylation

down-regulates activity

0.665

The activation of the mapk activity requires the dual phosphorylation of the ser/thr and tyr residues in the txy kinase activation motif (1113), and deactivation occurs through the action of either ser/thr protein phosphatase (14), protein-tyrosine phosphatase (ptp) (14, 15), or dual specificity phosphatases

SIGNOR-103035

Q08881

P19174

1

phosphorylation

up-regulates

0.637

In t cells, the predominant tec kinase is itk, which functions downstream of the t-cell receptor to regulate phospholipase c-gamma.

SIGNOR-165803

Q9H0M0

P36897

1

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

P14921

Q9UQM7

0

phosphorylation

down-regulates

0.309

Treatment of ets1 by t-cell nuclear extract or phosphorylation of these four serines by calmodulin-dependent kinase ii (camk ii) has recently been reported to decrease ets1 dna binding by reinforcing autoinhibition

SIGNOR-96334

P19235

Q9Y314

0

ubiquitination

up-regulates activity

0.331

Erythropoietin receptors associate with a ubiquitin ligase, p33RUL, and require its activity for erythropoietin-induced proliferation. This receptor-associated ubiquitin ligase, RUL, co-precipitated with EpoR from mammalian cells and mediated ubiquitination of EpoR. RUL mediates EpoR ubiquitination in COS7 cells and is inducibly ubiquitinated after Epo treatment. This observation is consistent with the lack of effects on EpoR stability by RUL-mediated ubiquitination in COS7 cells (Fig. 4).

SIGNOR-271477

P17612

P11831

1

phosphorylation

up-regulates

0.256

Myotonic dystrophy protein kinase (DMPK), a muscle- and neuron-restricted kinase, enhanced SRF-mediated promoter activity of the skeletal and cardiac alpha-actin genes in C2C12 myoblasts as well as in nonmyogenic cells. | Threonine 159 in the MADS box alphaI coil was a specific phosphorylation target in vitro as well as in vivo of both DMPK and protein kinase C-alpha.

SIGNOR-188177

P18847

Q99612

0

transcriptional regulation

up-regulates quantity by expression

0.394

KLF6 binds directly to and activates the ATF3 promoter.

SIGNOR-266051

P38936

Q9Y463

0

phosphorylation

up-regulates activity

0.258

Mirk exerts its anti-apoptotic effects during muscle differentiation at least in part through effects on the cell cycle inhibitor and pro-survival molecule p21cip1. Overexpression and rna interference experiments demonstrated that mirk phosphorylates p21 within its nuclear localization domain at ser-153 causing a portion of the typically nuclear p21 to localize in the cytoplasm.Translocation to the cytoplasm enables p21 to block apoptosis through inhibitory interaction with pro-apoptotic molecules.

SIGNOR-235635

O14578

P24844

1

phosphorylation

up-regulates activity

0.561

Activation of the catalytic ATPase domain residing in the N‐terminus of the heavy chain relies on the reversible phosphorylation of the associated MLC on Ser19 (monophosphorylation), or in some cases on both Thr18 and Ser19 (diphosphorylation)|We detected Ser19 of MLC as the common phosphorylation site for the catalytic domains of MRCK_/_, ROK_, MLCK and PAK_, but only ROK_ and CRIK are able to phosphorylate both Thr18 and Ser19 residues causing diphosphorylation.

SIGNOR-260306

P54132

Q13315

0

phosphorylation

up-regulates

0.775

Mitotic phosphorylation of blm was partially dependent on atm, and phosphorylation sites on blm were identified. A phosphospecific antibody against one of these sites (thr-99) revealed radiation-induced phosphorylation, which was defective in ataxia-telangiectasia cells. These data suggest that atm and blm function together in recognizing abnormal dna structures by direct interaction and that these phosphorylation sites in blm are important for radiosensitivity status but not for sce frequency.

SIGNOR-88010

Q9UBC3

P42658

1

transcriptional regulation

down-regulates quantity by repression

0.327

Dnmt3b was responsible for transcriptional silencing of Dpp6 gene as depletion of Dnmt3b resulted in increased mRNA and protein expression of Dpp6.

SIGNOR-268963

P31350

P06493

0

phosphorylation

down-regulates

0.504

We found that, during g2, following cdk-mediated phosphorylation of thr33, rrm2 is degraded via scf(cyclin f) to maintain balanced dntp pools and genome stability.

SIGNOR-197630

Q9BW19

P06493

0

phosphorylation

up-regulates quantity by stabilization

0.458

We confirmed that CDK1 phosphorylates Ser6 (Supplementary Fig S5B) and demonstrated that KIFC1 displays CDK1-mediated resistance to ubiquitination by the APC/C (Fig S5C).

SIGNOR-277294

Q13362-1

Q13315

0

phosphorylation

up-regulates activity

0.378

In the present study, we demonstrate that ataxia-telangiectasia mutated (ATM) directly phosphorylates and specifically regulates B56γ3, B56γ2 and B56δ, after DNA damage. We further show that phosphorylation of B56γ3 at Ser510 leads to an increase in B56γ3-PP2A complexes, and direction of PP2A phosphatase activity toward the substrate p53, activating its tumor-suppressive functions. we show that Ser510 phosphorylation significantly enhances the ability of B56γ3 to inhibit cell proliferation and anchorage-independent growth.

SIGNOR-276318

P03372

Q13153

0

phosphorylation

up-regulates

0.534

Pak1 directly phosphorylated the activation function-2 domain of the er at the n-terminal residue ser305, and its mutation to ala (s305a) abolished the pak1-mediated phosphorylation and transactivation functions of the er

SIGNOR-94206

P06493

Q9UKX7

1

phosphorylation

down-regulates

0.421

These results suggest that both ERK and Cdk1 directly phosphorylate Nup50 at Ser221 in intact cells|Notably, erk phosphorylation of the fg repeat region of nup50 reduced its affinity for importin-beta family proteins, importin-beta and transportin.

SIGNOR-188061

P28482

P17302

1

phosphorylation

down-regulates activity

0.608

These studies confirm that connexin-43 is a MAP kinase substrate in vivo and that phosphorylation on Ser255, Ser279, and/or Ser282 initiates the down-regulation of gap junctional communication. Studies with connexin-43 mutants suggest that MAP kinase phosphorylation at one or more of the tandem Ser279/Ser282 sites is sufficient to disrupt gap junctional intercellular communication.

SIGNOR-249401

Q9H9S0

Q05397

0

phosphorylation

up-regulates activity

0.274

In addition, FAK directly phosphorylates Nanog in a dose-dependent manner by in vitro kinase assay and in cancer cells in vivo. The site-directed mutagenesis of Nanog tyrosines, Y35F and Y174F, blocked phosphorylation and binding by FAK.

SIGNOR-276410

P21730

Q05655

0

phosphorylation

down-regulates

0.2

Whole cell phosphorylation assays with specific inhibitors as well as in vitro phosphorylation assays with recombinant enzymes and peptide substrates revealed that phosphorylation of ser-334 is regulated by protein kinase c-beta this study is among the first to analyze in a detailed manner, using a non-mutational approach, modifications of a defined phosphorylation site in a g protein-coupled receptor and to correlate these findings with functional parameters of receptor deactivation.

SIGNOR-73967

Q9Y2J4

Q9H0M0

0

ubiquitination

up-regulates activity

0.29

AMOTL2 mono-ubiquitination by WWP1 promotes contact inhibition by facilitating LATS activation|Here, we provide evidence that the E3 ligase WWP1 (WW-domain containing protein 1) mono-ubiquitinates AMOTL2 (angiomotin-like 2) at K347 and K408.

SIGNOR-271873

P59595

P53539

1

transcriptional regulation

up-regulates quantity by expression

0.2

The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well

SIGNOR-260728

O60285

Q96QC0

1

phosphorylation

up-regulates activity

0.2

Here, we show that NUAK1 is a predominantly nuclear protein that associates with a network of nuclear protein phosphatase 1 (PP1) interactors and that PNUTS, a nuclear regulatory subunit of PP1, is phosphorylated by NUAK1.|Inhibition of NUAK1 abolishes chromatin association of PNUTS, reduces spliceosome activity, and suppresses nascent RNA synthesis.

SIGNOR-280051

P53350

Q9UBB4

1

phosphorylation

down-regulates

0.353

Phosphorylation of ataxin-10 by polo-like kinase 1 is required for cytokinesis. Plk1 phosphorylates ataxin-10 at s77 and t82 in vitro. we found that ataxin-10 is ubiquitinated, and is subject to proteasome-dependent degradation, which is delayed in the 2a mutant. We propose a model in which plk1 phosphorylation of ataxin-10 influences its degradation and cytokinesis

SIGNOR-176122

Q07666

P06213

0

phosphorylation

up-regulates activity

0.363

Thus, Tyr phosphorylation of Sam68 by IR could modulate its association with the splicing machinery in a similar way to that described for p59 fyn, and this way, it could influence splice site selection.

SIGNOR-278946

P41229

P68431

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-264305

Q13547

O95471

1

transcriptional regulation

down-regulates quantity by repression

0.2

ChIP assays revealed that SNAI1P is recruited on the CLDN7 gene promoter along with the co-repressor CtBP1 and the effector HDAC1.|These data further suggest that HDAC1 is involved in the SNAI1P-mediated repression of the human CLDN7 gene promoter.

SIGNOR-254106

O43638

P98177

1

transcriptional regulation

down-regulates quantity by repression

0.2

Fkhl18 suppressed the transcriptional activity of FoxO3a and FoxO4.

SIGNOR-261611

Q8IUH4

Q01726

1

palmitoylation

up-regulates activity

0.274

Collectively these results suggest that ZDHHC13 phosphorylation by ATR following UVB irradiation promotes its interaction with MC1R to stimulate MC1R palmitoylation.Activating MC1R palmitoylation rescues the defect of MC1R RHC variants

SIGNOR-273518

Q86WB0

P24941

0

phosphorylation

down-regulates

0.2

Moreover, we found cyclin b1/cdk1 to phosphorylate nipa at ser-395 in mitosis. Mutation of both ser-359 and ser-395 impaired effective inactivation of the scfnipa complex, resulting in reduced levels of mitotic cyclin b1

SIGNOR-154051

P45985

Q99683

0

phosphorylation

up-regulates activity

0.631

A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subs of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase)

SIGNOR-45373

P19419

Q16539

0

phosphorylation

up-regulates

0.526

We demonstrate here that elk-1 is barely activated by a third subclass of map kinases (p38), most likely because the critical residues ser383 and ser389 are poorly phosphorylated by p38 map kinase.

SIGNOR-47630

P05771

P28329

1

phosphorylation

up-regulates

0.286

Protein kinase c isoforms differentially phosphorylate human choline acetyltransferase regulating its catalytic activity.

SIGNOR-129288

Q99814

Q9Y4C1

1

transcriptional regulation

up-regulates quantity by expression

0.265

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-271583