GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q00987	Q9Y6B2	1	polyubiquitination	down-regulates quantity by destabilization	0.424	Degradation of EID-1 occurs via ubiquitin-dependent proteolysis and correlates with MDM2 binding. These results are consistent with a model wherein destruction of EID-1 is linked to its ability to interact with MDM2 via either p300 or pRB.	SIGNOR-272582
Q14669	Q8IYW5	1	ubiquitination	down-regulates activity	0.465	Here, we show that TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage. We find that RNF168 can be saturated by increasing amounts of DSBs. Depletion of TRIP12 and UBR5 allows accumulation of RNF168 to supraphysiological levels, followed by massive spreading of ubiquitin conjugates and hyperaccumulation of ubiquitin-regulated genome caretakers such as 53BP1 and BRCA1.	SIGNOR-266783
P05771	P29474	1	phosphorylation	down-regulates activity	0.309	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-251630
Q92934	P42574	0	cleavage	up-regulates activity	0.536	Casp3 cleaves bad at asp-61. In addition, caspases convert bad(l) into a pro-death fragment that resembles the short splice variant.	SIGNOR-126727
O75582	P47712	1	phosphorylation	up-regulates activity	0.352	Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases.	SIGNOR-249051
P45984	Q9Y2Y9	1	phosphorylation	down-regulates quantity by destabilization	0.2	TGF-β-mediated downregulation of KLF13 by HDAC-mediated epigenetic silencing and JNK-induced phosphorylation abrogates the latter’s inhibitory effect on TGF-β signaling.	SIGNOR-277809
Q06187	Q15417	1	phosphorylation	up-regulates quantity	0.2	Co-expression of calponin-3 with various kinases in S2 Schneider cells promoted a phosphorylation of calponin-3 by Syk, but also by the Tec family kinase Btk.	SIGNOR-280196
P67775	Q9H0H5	1	dephosphorylation	down-regulates	0.303	We report here that (i) mgcracgap is phosphorylated by aurora b and cdk1, (ii) pp2a dephosphorylates aurora b and cdk1 phosphorylated sites and (iii) inhibition of pp2a abrogates mgcracgap/ect2 interaction. Therefore, pp2a may regulate cytokinesis by dephosphorylating mgcracgap and its interacting partners.	SIGNOR-160398
P10147	Q92794	0	transcriptional regulation	up-regulates quantity by expression	0.2	We further demonstrate that the histone acetyltransferase, MOZ, can activate the MIP-1a promoter in T-cells and that this activation is largely dependent upon the proximal RUNX site. Moreover, we show that co-expression of MOZ and RUNX1 can activate the MIP-1a promoter.	SIGNOR-251726
P54259	P45983	0	phosphorylation	down-regulates activity	0.376	Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-jun nh2-terminal kinase. serine 734 of the drpla protein is a phospho-acceptor site by jnk. The phosphorylation may be coupled to the activation of a protease. The molecular size of drpla protein detected in the rat brain with the specific phosphopeptide antibody was 150_kda, which was slightly smaller than that expected from the sequence and the results with the human protein. The phosphorylated forms of ha-tagged human drpla gradually disappeared after osmotic treatment,	SIGNOR-102398
Q00535	Q9GZM8	1	phosphorylation	up-regulates activity	0.772	Three specific phosphorylation sites (Ser198, Thr219 and Ser231) and two weak phosphorylation sites (Ser242 and Thr245) for CDK5/p35 are located in this region of NUDEL \| Each single or double mutant compromised,and the triple mutant completely eliminated, interaction with 14-3-3ε. \| 14-3-3ε sustains NUDEL phosphorylation and protects it from phosphatase.e dynein motor function.	SIGNOR-250676
P51812	P49840	1	phosphorylation	down-regulates activity	0.265	P90-rsk and akt may promote rapid phosphorylation/inactivation of glycogen synthase kinase 3 in chemoattractant-stimulated neutrophils. These reactions were monitored with a phosphospecific antibody that only recognized the alpha- or beta-isoforms of GSK-3 when these proteins were phosphorylated on serine residues 21 and 9, respectively.	SIGNOR-110827
P17252	P17812	1	phosphorylation	down-regulates	0.2	These data indicated that protein kinase c phosphorylation at ser(462) stimulates human ctp synthetase 1 activity, whereas phosphorylation at thr(455) inhibits activity.	SIGNOR-154621
P27361	Q9BVJ7	0	dephosphorylation	down-regulates activity	0.31	In particular, DUSP23 can dephosphorylate and inactivate MAPK3 ( xref ).\|In particular, DUSP23 can dephosphorylate and inactivate MAPK3.	SIGNOR-277103
Q6PML9	P49757	1	ubiquitination	down-regulates quantity by destabilization	0.2	Lnx functions as a ring type e3 ubiquitin ligase that targets the cell fate determinant numb for ubiquitin-dependent degradation.	SIGNOR-113704
Q13309	P48735	1	ubiquitination	down-regulates quantity by destabilization	0.2	During the cell cycle S phase, Cyclin A-CDK2 phosphorylates IDH1 on its Threonine 157 residue (Threonine 197 in IDH2) to facilitate its recognition and ubiquitination by Skp2 E3 ubiquitin, followed by degradation through 26S proteasome	SIGNOR-267626
P48454	Q92934	1	dephosphorylation	up-regulates activity	0.399	Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD\|Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis.	SIGNOR-248529
P28749	P67775	0	dephosphorylation	up-regulates	0.623	Pocket protein family consists of the retinoblastoma tumor suppressor protein (prb) and the functionally and structurally related proteins p107 and p130./dephosphorylation of p130 and p107 in cell extracts is inhibited by concentrations of okadaic acid known to inhibit pp2a, but not pp1. Finally, the pp2a catalytic subunit pp2a/c) specifically interacts with both p130 and p107 / the cell cycle repressor activity of pocket proteins is inactivated by cdk mediated phosphorylation.	SIGNOR-129749
Q13976	P78347	1	phosphorylation	up-regulates	0.569	G-kinase phosphorylated tfii-i in vitro and in vivo on ser(371) and ser(743) outside of the interaction domain. G-kinase strongly enhanced tfii-i transactivation of a serum-response element-containing promoter in cos7 cells	SIGNOR-89849
P42772	Q9HCX3	0	transcriptional regulation	down-regulates quantity by repression	0.28	Finally, we show that ZNF304 also directs transcriptional silencing of INK4-ARF in human embryonic stem cells.	SIGNOR-266099
P45983	P85298	1	phosphorylation	up-regulates activity	0.327	Furthermore, we identify that BPGAP1 (a BCH domain-containing, Cdc42GAP-like Rho GTPase-activating protein) promotes MEK partner 1 (MP1)-induced ERK activation on late endosome through scaffolding MP1/MEK1 complex. This regulatory function requires phosphorylation of BPGAP1 by JNK at its C terminal tail (Ser424) to unlock its autoinhibitory conformation.	SIGNOR-275550
Q07955	P49759	0	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
Q14653	Q9UHD2	0	phosphorylation	up-regulates activity	0.822	Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404.	SIGNOR-178420
Q00535	P46527	1	phosphorylation	down-regulates activity	0.643	CDK5 knockdown in HEY cells significantly prolonged the half-life of TP53 and p27 Kip1 proteins (XREF_FIG).\|During neural stem cell differentiation, CDK5 can phosphorylate p27 at Thr187 and at Ser10, promoting neurite outgrowth as neurons differentiate .	SIGNOR-279681
P08047	Q92820	1	transcriptional regulation	up-regulates quantity by expression	0.2	Overexpression of Sp1 led to enhanced GGH promoter activity and GGH mRNA expression in allele-specific manners. These findings suggested that Sp1 acted as a positive regulator of human GGH transcription through the rs3758149 polymorphism in CEM/C1 cells.	SIGNOR-261350
P31749	P78362	1	phosphorylation	up-regulates	0.465	Here we show that srpk2, a protein kinase specific for the serine/arginine (sr) family of splicing factors, triggers cell cycle progression in neurons and induces apoptosis through regulation of nuclear cyclin d1. Akt phosphorylates srpk2 on thr-492 and promotes its nuclear translocation leading to cyclin d1 up-regulation, cell cycle reentry, and neuronal apoptosis.	SIGNOR-186760
P06493	P23769	1	phosphorylation	down-regulates quantity by destabilization	0.355	GATA2 contains a cell division control protein 4 (Cdc4) phosphodegron (CPD), a consensus motif for ubiquitylation by Fbw7, which includes Thr(176). Ectopic expression of Fbw7 destabilized GATA2 and promoted its proteasomal degradation. Substitution of threonine 176 to alanine in GATA2 inhibited binding with Fbw7, and the ubiquitylation and degradation of GATA2 by Fbw7 was suppressed. The CPD kinase, which mediates the phosphorylation of Thr(176), was cyclin B-cyclin-dependent kinase 1 (CDK1).	SIGNOR-276884
Q15831	P60484	1	phosphorylation	down-regulates activity	0.604	The C-terminal tail of PTEN is also the target of mutations in tumors. As mentioned, this region contains the main phosphorylation sites mapped to residues Ser362, Thr366, Ser370, Ser380, Thr382, Thr383, and Ser385, and the kinases involved are casein kinase 2 (CK2), GSK3_, LKB1, and MAST.84,97-101 The phosphorylation of the tail has been shown to enhance PTEN stability but at the same time decrease its phosphatase activity	SIGNOR-161118
Q12879	P06241	0	phosphorylation	up-regulates activity	0.734	To gain further insight into the roles of Src and Fyn in the phosphorylation and regulation of the NMDA receptor, we have characterized the tyrosine phosphorylation of NR2A and NR2B by exogenous Src and FynIn the case of NR2A, three potential tyrosine phosphorylation sites have been proposed: Tyr1105, Tyr1267 and Tyr1387 (Zheng et al. 1998; Bi et al. 2000), all of which are similarly located in the C-terminal, cytoplasmic domain.	SIGNOR-247151
P28329	P17252	0	phosphorylation	up-regulates	0.383	We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation.	SIGNOR-129264
Q12955	Q14576	0	post transcriptional regulation	down-regulates quantity	0.25	NElavl (composed of Elavl2, Elavl3, and Elavl4) proteins are the RNA-binding proteins that is specifically expressed in neurons, regulate the alternative splicing of target RNAs, and promote neuronal differentiation and maturation. Here, we found that the alternative splicing of AnkyrinG exon 34 was misregulated in the cerebella of Elavl3-/- mice. AnkyrinG is an essential factor for the formation of neuronal polarity and is required for normal neuronal functions.	SIGNOR-266861
P33778	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265385
P08047	O00141	0	phosphorylation	up-regulates activity	0.265	In fact, SGK1 activates and phosphorylates SP1 on serine 59, a regulator of nucleocytoplasmic trafficking related genes .\|In fact, SGK1 activates and phosphorylates SP1 on serine 59, a regulator of nucleocytoplasmic trafficking-related genes xref .	SIGNOR-279246
P11678	P12724	1	post translational modification	up-regulates activity	0.477	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-261705
Q00987	P06400	1	ubiquitination	down-regulates quantity by destabilization	0.667	In this study, we found that Mdm2, a ubiquitin ligase for p53, promoted ubiquitin-dependent degradation of pRB	SIGNOR-278530
Q8WUI4	O43318	0	phosphorylation	down-regulates	0.2	We further show that emk and c-tak1 phosphorylate class iia hdacs on one of their multiple 14-3-3 binding sites and alter their subcellular localization and repressive function	SIGNOR-149579
P49841	Q12888	1	phosphorylation	up-regulates activity	0.283	Based on these observations, we hypothesized that the IR induced GSK3beta nuclear translocation may activate 53BP1 via phosphorylation at the S/T-Q motif.\|Importantly, our in vivo and in vitro data clearly indicated that GSK3\u03b2 induced the phosphorylation of 53BP1 at the Ser166 site.	SIGNOR-278226
Q12857	P54756	1	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268895
P09769	P43405	1	phosphorylation	up-regulates activity	0.594	Fgr associates with Fc\u03b5RI and phosphorylates Syk in antigen-stimulated mast cells.\|The overexpression of Fgr stimulates Syk, Syk dependent signaling molecules, and degranulation in RBL-2H3 cells and BMMCs.	SIGNOR-279332
P51812	P04637	1	phosphorylation	up-regulates activity	0.336	Here we show that ribosomal S6 kinase 2 (RSK2) activates and phosphorylates p53 (Ser15) in vitro and in vivo and colocalizes with p53 in the nucleus.	SIGNOR-279567
P60484	Q13285	1	dephosphorylation	down-regulates activity	0.256	The fact that SF-1 and PIP3 is robustly dephosphorylated by PTEN, yet SF-1 and PIP2 is resistant to phosphorylation by p110 PI3-kinases, suggests that nuclear proteins like SF-1 can help decouple PTEN signaling in the nucleus from p110 signaling.\|We also showed that PTEN can dephosphorylate the SF-1 and PIP3 product of the IPMK reaction, and that PTEN inhibits SF-1 transcriptional activity.	SIGNOR-277117
Q9NPD5	P20823	0	transcriptional regulation	up-regulates quantity by expression	0.251	Farnesoid X receptor, hepatocyte nuclear factors 1alpha and 3beta are essential for transcriptional activation of the liver-specific organic anion transporter-2 gene.\|This study demonstrated that the transcription of the LST-2 gene is regulated by three transcription factors, FXR, HNF1alpha, and HNF3beta.	SIGNOR-268988
Q99576	Q53ET0	0	transcriptional regulation	up-regulates quantity	0.2	CRTC2 knockdown attenuates glucocorticoid-responsive GILZ mRNA expression in HeLa cells	SIGNOR-256109
O15530	P53350	1	phosphorylation	up-regulates activity	0.2	Here, we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces MYC phosphorylation and protein accumulation. We show that PDK1-PLK1-MYC signaling is critical for cancer cell growth and survival, and small-molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting of MYC dependency	SIGNOR-243519
Q9BPU6	P49841	0	phosphorylation	up-regulates activity	0.431	The T516 phosphorylation was achieved by the glycogen synthase kinase-3beta (GSK-3beta), which can phosphorylate the wildtype protein but not the non-phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin-binding property of CRMP5. Therefore, CRMP5-induced growth inhibition is dependent on T516 phosphorylation through the GSK-3beta pathway.	SIGNOR-264835
P31269	P06748	0	transcriptional regulation	down-regulates quantity by repression	0.352	In AML cells, NPM1 mutations result in abnormal cytoplasmic localization of the mutant protein (NPM1c); however, it is unknown whether NPM1c is required to maintain the leukemic state. Here, we show that loss of NPM1c from the cytoplasm, either through nuclear relocalization or targeted degradation, results in immediate downregulation of homeobox (HOX) genes followed by differentiation.	SIGNOR-260138
Q00526	Q12800	1	phosphorylation	down-regulates	0.264	In vitro, lsf is phosphorylated by cyclin e/cyclin-dependent kinase 2 (cdk2), cyclin c/cdk2, and cyclin c/cdk3, predominantly on s309. Phosphorylation by cyclin c/cyclin-dependent kinase 2 following mitogenic stimulation of murine fibroblasts inhibits transcriptional activity of lsf during g1 progression	SIGNOR-184164
P13349	P17661	1	transcriptional regulation	up-regulates quantity by expression	0.241	Desmin, the muscle specific intermediate filament (IF) protein, is expressed at low levels in myoblasts and at the onset of differentiation its expression increases several fold. In an effort to explore the mechanism involved in the tissue-specific and developmentally regulated expression of desmin, we have isolated the mouse desmin gene.Co-transfection of myoD, myogenin, MRF4 and Myf5, with the desmin-CAT construct into 10T-1/2 cells demonstrated that all these factors could transactivate desmin gene expression	SIGNOR-241494
Q13315	O43684	1	phosphorylation	up-regulates activity	0.312	Taken together, we highlight the functional significance of the crosstalk between the kinetochore-oriented signal and double-strand break repair pathways via ATM phosphorylation of Bub3 on Ser135.	SIGNOR-277582
Q99717	Q9HCE7	0	ubiquitination	down-regulates	0.769	Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps.	SIGNOR-195663
P36956	Q5VTR2	0	ubiquitination	down-regulates activity	0.425	Here, we reveal that RNF20-induced SREBP1c ubiquitination down-regulates hepatic lipogenic activity upon PKA activation.\|Overexpression of RNF20 represses SREBP1c activity, leading to a decrease in the expression of lipogenic genes.	SIGNOR-278643
P41182	Q9BZL6	0	phosphorylation	down-regulates activity	0.2	Prkd2 directly binds to Bcl6 and Prkd2-dependent phosphorylation of Bcl6 is necessary to constrain Bcl6 to the cytoplasm, thereby limiting TFH development.	SIGNOR-279651
Q09472	P04637	1	polyubiquitination	down-regulates quantity by destabilization	0.912	P53 is stabilized by the binding of p300 to the oncoprotein E1A, suggesting that p300 regulates p53 degradation. Purified p300 exhibited intrinsic ubiquitin ligase activity that was inhibited by E1A. In vitro, p300 with MDM2 catalyzed p53 polyubiquitination, whereas MDM2 catalyzed p53 monoubiquitination. E1A expression caused a decrease in polyubiquitinated but not monoubiquitinated p53 in cells. Thus, generation of the polyubiquitinated forms of p53 that are targeted for proteasome degradation requires the intrinsic ubiquitin ligase activities of MDM2 and p300.	SIGNOR-271418
O00429	Q00535	0	phosphorylation	up-regulates activity	0.464	CDK5 activates DRP1 in BTICs.\|To determine if CDK5 could directly phosphorylate DRP1, we performed an in vitro kinase assay with CDK5, its regulatory partner p25 and GST-DRP1 (wild type or S616A mutant) and found that CDK5 directly phosphorylates DRP1 on the S616 site (Fig. 7d).	SIGNOR-278275
Q13501	Q99759	0	phosphorylation	up-regulates activity	0.556	MEKK3 overexpression, but not that of a kinase dead mutant, was able to induce the phosphorylation of p62 at T269 and S272 (XREF_FIG), which correlated with mTORC1 activation (XREF_FIG), suggesting that MEKK3 could be a bona fide regulator of p62 phosphorylation and mTORC1 activity.	SIGNOR-279532
O96017	P30304	1	phosphorylation	down-regulates quantity by destabilization	0.843	We show that IR-induced destruction of Cdc25A requires both ATM and the Chk2-mediated phosphorylation of Cdc25A on serine 123.	SIGNOR-106808
P46937	O75385	0	phosphorylation	up-regulates quantity by stabilization	0.2	Mechanistically, hypoxia stimulates ULK1 to translocate into nucleus, where it interacts with and phosphorylates yes-associated protein (YAP) at Ser227, resulting in YAP stabilization through blockade of ubiquitin-proteasome system (UPS), which in turn facilitates PKM2 transcription, glycolysis, cell proliferation in vitro as well as PDAC growth in mice.	SIGNOR-277570
P12931	Q9H2X6	1	phosphorylation	up-regulates activity	0.307	Using mass spectrometry we identified 9 Src-mediated Tyr-phosphorylation sites within HIPK2, 5 of them positioned in the kinase domain.\|We demonstrate that ectopic expression of Src increases the half-life of HIPK2 by interfering with Siah-1-mediated HIPK2 degradation.	SIGNOR-278989
P46531	Q16566	0	phosphorylation	up-regulates quantity by stabilization	0.36	In summary, we have found that phosphorylation of Notch1-IC by CaMKIV inhibits the proteasomal degradation of Notch1-IC through Fbw7 ( Fig.\u00a07 ).	SIGNOR-279596
P10276	P31749	0	phosphorylation	down-regulates	0.602	We report that akt, which is constitutively activated in nsclc cells, phosphorylates raralpha and inhibits its transactivation. / mutation of ser96 to alanine abrogated the suppressive effect of akt.	SIGNOR-252489
Q99759	O14920	1	phosphorylation	up-regulates activity	0.569	Genetic analysis showed that MEKK3, which is thought to activate IKK2 through phosphorylation (Yang et al., 2001), is necessary for TNF-alpha-induced NF-kappaB activation.\|Our results also suggest that IKK2 is phosphorylated on S177 and S181 on its activation loop by MEKK3.	SIGNOR-279468
Q7KZI7	Q6WKZ4	1	phosphorylation	up-regulates quantity	0.341	We have now found that MARK2 phosphorylates Rab11-FIP1B/C at serine 234 in a consensus site similar to that previously identified in Rab11-FIP2.	SIGNOR-273676
P46695	P28482	0	phosphorylation	up-regulates	0.552	Upon phosphorylation by erks, iex-1 acquires the ability to inhibit cell death induced by various stimuli. In turn, iex-1 potentiates erk activation in response to various growth factors.	SIGNOR-93740
P68400	P01106	1	phosphorylation	down-regulates quantity by destabilization	0.504	Together, our findings provide evidence for CK1α-mediated destruction of c-Myc and identify c-Myc S252 as a crucial CK1α phosphorylation site for c-Myc degradation.	SIGNOR-276388
Q14493	P84243	1	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265418
Q99638	Q9UKI8	0	phosphorylation	up-regulates	0.448	Tlk1b phosphorylates hrad9 at s328 after the induction of dsb, occupancy of rad9 adjacent to the break increased during repair while that of asf1 decreased, and the effect was more pronounced in tlk1b-overexpressing cells. We propose that following genotoxic stress, tlk1/1b is first recruited to the dsb in a complex with rad9. It then exchanges with asf1 to promote nucleosomes eviction at the dsb and access of the repair machinery to unencumbered dna.	SIGNOR-181748
Q15417	P06241	0	phosphorylation	down-regulates activity	0.333	We identify, for the first time, tyrosine-phosphorylated calponin h3 within COS 7 cells, before and after their transfection with the pSV vector containing cDNA encoding the cytoplasmic, Src-related, tyrosine kinase, Fyn. we have localized the tyrosines phosphorylated without actin to Tyr261 in calponin h3 and to Tyr261 and Tyr182 in calponin h1. Tyrosine phosphorylation of calponins inhibits their binding to F-actin	SIGNOR-251159
P06239	P24666	1	phosphorylation	up-regulates activity	0.354	In co-transfected COS cells, Lck and Fyn caused phosphorylation of LMPTP. Most of the phosphate was located at Tyr-131, and some was also located at Tyr-132. Site-directed mutagenesis showed that Tyr-131 is important for the catalytic activity of LMPTP, and that thiophosphorylation of Tyr-131, and to a lesser degree Tyr-132, is responsible for the activation.	SIGNOR-251367
P04792	Q13237	0	phosphorylation	down-regulates	0.2	Purified pkg isoforms ia, ib, and ii all caused incorporation of phosphate in recombinant hsp27 at ser-78, ser-82, and thr-143, but not ser-15.These Studies indicate that hsp27 is a genuine substrate for pkg and that pkg may mediate inhibition of platelet aggregation through phosphorylation of hsp27 and subsequent prevent of actin polymerization	SIGNOR-186947
O00429	Q13546	0	phosphorylation	up-regulates activity	0.51	RIPK1 also activates DRP1 by phosphorylating DRP1 at Ser616 in a RIPK3-dependent fashion independent of MLKL.	SIGNOR-280104
Q06330	P38936	1	transcriptional regulation	up-regulates quantity by expression	0.307	Induction of the p21WAF1/Cip1 gene by Notch 1 activation in differentiating keratinocytes is associated with direct targeting of the RBP-J_ protein to the p21 promoter.	SIGNOR-252032
Q92630	P10070	1	phosphorylation	down-regulates quantity by destabilization	0.3	DYRK2 directly phosphorylated Gli2 sequences and resulted in the loss of coexpressed GLI proteins, indicating that DYRK2 acts by inducing the phosphorylation and degradation of GLI proteins via the ubiquitin and proteasome pathway.	SIGNOR-279034
P29353	P23470	0	dephosphorylation	down-regulates activity	0.2	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254724
Q92530	O95271	0	ADP-ribosylation	down-regulates quantity by destabilization	0.501	We identify the ADP-ribosyltransferase tankyrase (TNKS) and the 19S assembly chaperones dp27 and dS5b as direct binding partners of the proteasome regulator PI31. TNKS-mediated ADP-ribosylation of PI31 drastically reduces its affinity for 20S proteasome alpha subunits to relieve 20S repression by PI31.	SIGNOR-263387
Q9Y572	Q13490	0	polyubiquitination	up-regulates activity	0.677	CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.	SIGNOR-272711
P06493	P23443	1	phosphorylation	up-regulates	0.384	Interestingly, phosphorylation at several ser/thr residues within the c-terminal autoinhibitory tail appears to either activate or inhibit s6k1, depending on the cell cycle phase. phosphorylation of those residues (featured by the thr-421/ser-424 site) during mitosis pursued by cdk1 inactivates s6k1 we then assessed the phosphorylation status of the mitosis-specific inhibitory residue of s6k1, thr-421/ser-424, which is targeted by mitotic cdk1.	SIGNOR-111507
Q13177	P01106	1	phosphorylation	down-regulates activity	0.649	Here we demonstrate that Pak2 phosphorylates Myc at three sites (T358, S373, and T400) and affects Myc functions both in vitro and in vivo.	SIGNOR-278489
P06241	Q9ULL1	1	phosphorylation	up-regulates activity	0.2	We also show that this activation of PLEKHG1 by FYN requires interaction between these two proteins and FYN-induced tyrosine phosphorylation of PLEKHG1 .\|We also show that this activation of PLEKHG1 by FYN requires interaction between these two proteins and FYN-induced tyrosine phosphorylation of PLEKHG1.	SIGNOR-279988
Q9NWT8	O14965	0	phosphorylation	up-regulates quantity by stabilization	0.681	AIP is phosphorylated on Serine 70 by Aurora‐A but not Aurora‐B and expression of phosphorylation mimic mutant of AIP results in prolonged protein stability compared to unphosphorylatable mutant. Phosphorylation of AIP Prolongs its Protein Stability	SIGNOR-262648
Q96PY5	P06493	0	phosphorylation	up-regulates activity	0.2	In this study we have identified the formin FMNL2 as a novel substrate for CDK1 that plays a role in maintaining adhesion complexes and facilitates cell cycle–dependent changes in adhesion complexes. Knockdown of FMNL2 or expression of a nonphosphorylatable S1016A mutant resulted in the loss of adhesion complexes and stress fibers within the cell body, with peripheral structures being maintained.	SIGNOR-273555
P28482	Q08493	1	phosphorylation	down-regulates	0.256	The short-form pde4b2 isoenzyme was activated by erk2 phosphorylation. sub-family selective actions in the ability of erk2 map kinase to phosphorylate and regulate the activity of pde4 cyclic amp-specific phosphodiesterases	SIGNOR-83187
Q15672	P45983	0	phosphorylation	up-regulates	0.308	Phosphorylation of serine 68 of twist1 by mapks stabilizes twist1 protein and promotes breast cancer cell invasiveness.	SIGNOR-173417
P24928	O00308	0	ubiquitination	down-regulates quantity	0.387	WWP2 ubiquitylates RNA polymerase II for DNA-PK-dependent transcription arrest and repair at DNA breaks\|In response to DSBs, WWP2 targets the RNAPII subunit RPB1 for K48-linked ubiquitylation, thereby driving DNA-PK- and proteasome-dependent eviction of RNAPII.	SIGNOR-268851
P04626	O14672	0	cleavage	up-regulates activity	0.344	The ADAM proteases are best known for their role in shedding the extracellular domain of transmembrane proteins. Among the transmembrane proteins shed by ADAM10 are notch, HER2, E-cadherin, CD44, L1 and the EGFR ligands, EGF and betacellulin.	SIGNOR-259845
Q14938	O75093	1	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268906
P23467	P28482	1	dephosphorylation	down-regulates	0.382	Expression of rptp-beta inhibits both mek1/2 and erk1/2 phosphorylation.	SIGNOR-173000
Q9H1D0	P18031	0	dephosphorylation	down-regulates activity	0.631	In HEK293 cells, transfected with the Ca2+ channel protein TRPV6, Ca2+ influx is increased and TRPV6 is tyrosine phosphorylated following addition of the tyrosine phosphatase inhibitor\|PTP1B interacts with the N-terminal domain of TRPV6 within a region of amino acids 1-191 as shown by co-immunoprecipitation, bimolecular fluorescence complementation and the yeast 2-hybrid system. Point mutation of both tyrosines 161 and 162 in the TRPV6 protein abolishes the DMHV-effect on Ca2+ influx and tyrosine phosphorylation by Src. Single mutations of Y161 or Y162 shows that each of both tyrosines alone is sufficient for the DMHV-effect. We conclude that phosphorylation/dephosphorylation of tyrosines in position 161 and 162 is essential for regulation of Ca2+ influx through TRPV6 Ca2+ channels in HEK293 cells.	SIGNOR-248433
Q9Y6A5	O14965	0	phosphorylation	up-regulates activity	0.937	We show that this conserved serine on human TACC3 (Ser(558)) is also phosphorylated by Aurora A. Moreover, phosphorylation of TACC3 by Aurora A in human cells is essential for its proper localization to centrosomes and proximal mitotic spindles. Inhibition of Aurora A with the selective small molecule inhibitor MLN8054 in cultured human tumor cells resulted in mislocalization of TACC3 away from mitotic spindles in a concentration-dependent manner.	SIGNOR-262655
Q05655	Q9UQ13	1	phosphorylation	down-regulates quantity by destabilization	0.2	PKCalpha/delta phosphorylate Sur8 at Thr-71 and Ser-297, respectively. This phosphorylation is essential for polyubiquitin-dependent degradation of Sur8.	SIGNOR-275565
P08473	P68400	0	phosphorylation	down-regulates	0.323	The cytoplasmic n-terminal domain of nep interacts with the phosphatase and tensin homologue deleted on chromosome 10 (pten) thereby regulating intracellular signaling via akt. Ser 6 is efficiently phosphorylated by protein kinase ck2. The phosphorylation of the cytoplasmic domain of nep inhibits its interaction with pten.	SIGNOR-168673
P21731-2	P25098	0	phosphorylation	down-regulates activity	0.2	These data suggest a model whereby agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling, profoundly desensitizing signalling, and promotes beta-arrestin association and, in turn, facilitates TPbeta internalization.	SIGNOR-274088
P23528	Q76I76	0	dephosphorylation	up-regulates activity	0.732	Differential activities, subcellular distribution and tissue expression patterns of three members of Slingshot family phosphatases that dephosphorylate cofilin.\|Cofilin, a key regulator of actin filament dynamics, is inactivated by phosphorylation at Ser-3 by LIM-kinases and is reactivated by dephosphorylation by a family of protein phosphatases, termed Slingshot (SSH).	SIGNOR-248733
P49815	O15111	0	phosphorylation	down-regulates	0.296	Insulin activation of mtor requires akt in a manner that involves ikkalpha, preferentially to ikkbeta, and tsc2 phosphorylation	SIGNOR-178664
P28482	O15027	1	phosphorylation	up-regulates activity	0.352	Recombinant active ERK2 also phosphorylated Sec16 (XREF_FIG).	SIGNOR-280022
Q5SQI0	Q9BQE3	1	acetylation	up-regulates quantity by stabilization	0.246	Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.\|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules	SIGNOR-272247
P17612	P13224	1	phosphorylation	down-regulates activity	0.312	Platelet glycoprotein Ib beta is phosphorylated on serine 166 by cyclic AMP-dependent protein kinase. phosphorylation of this residue may contribute to the inhibitory actions of cyclic AMP by inhibiting collagen-induced polymerization of actin.	SIGNOR-249986
Q8WU20	P21802	0	phosphorylation	up-regulates activity	0.777	In this report, we demonstrate that FGF stimulation induces tyrosine phosphorylation of a novel lipid anchored docking protein, termed FRS2, that forms a complex with Grb2/Sos, thus linking FGF-receptor activation to the Ras/MAPK signaling pathway.	SIGNOR-236950
P62136	Q02447	1	dephosphorylation	down-regulates activity	0.2	Transcription factors Sp1 and Sp3 activate alpha-ENaC2 transcription through a GC-rich element (Sp1-binding site) in the promoter. Sp1 and Sp3 are essential for alpha-ENaC2 transcription in lung epithelial cells and that dephosphorylation of the Sp transcription factors by PP1 suppresses alpha-ENaC2 expression.	SIGNOR-251953
Q15019	P68400	0	phosphorylation	down-regulates	0.2	Here we show that human septin 2 is phosphorylated in vivo at ser218 by casein kinase ii. Septin 2 binds and hydrolyses gtp. The purified protein has the capacity to polymerize into long filaments when loaded with gtp or gdp. Moreover, we show that the endogenous protein in hela cells, like that produced in insect cells, is phosphorylated by casein kinase ii and that this phosphorylation alters nucleotide binding.	SIGNOR-148010
Q13315	Q9BW19	1	phosphorylation	up-regulates quantity by stabilization	0.2	ATM and ATR kinases phosphorylate KIFC1-S26 during DNA-damage conditions.KIFC1 was stabilized upon phosphorylation and thus promoted centrosome clustering, CIN, and tumor recurrence both in vivo and in vitro.	SIGNOR-277295

Q00987

Q9Y6B2

1

polyubiquitination

down-regulates quantity by destabilization

0.424

Degradation of EID-1 occurs via ubiquitin-dependent proteolysis and correlates with MDM2 binding. These results are consistent with a model wherein destruction of EID-1 is linked to its ability to interact with MDM2 via either p300 or pRB.

SIGNOR-272582

Q14669

Q8IYW5

1

ubiquitination

down-regulates activity

0.465

Here, we show that TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage. We find that RNF168 can be saturated by increasing amounts of DSBs. Depletion of TRIP12 and UBR5 allows accumulation of RNF168 to supraphysiological levels, followed by massive spreading of ubiquitin conjugates and hyperaccumulation of ubiquitin-regulated genome caretakers such as 53BP1 and BRCA1.

SIGNOR-266783

P05771

P29474

1

phosphorylation

down-regulates activity

0.309

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-251630

Q92934

P42574

0

cleavage

up-regulates activity

0.536

Casp3 cleaves bad at asp-61. In addition, caspases convert bad(l) into a pro-death fragment that resembles the short splice variant.

SIGNOR-126727

O75582

P47712

1

phosphorylation

up-regulates activity

0.352

Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases.

SIGNOR-249051

P45984

Q9Y2Y9

1

phosphorylation

down-regulates quantity by destabilization

0.2

TGF-β-mediated downregulation of KLF13 by HDAC-mediated epigenetic silencing and JNK-induced phosphorylation abrogates the latter’s inhibitory effect on TGF-β signaling.

SIGNOR-277809

Q06187

Q15417

1

phosphorylation

up-regulates quantity

0.2

Co-expression of calponin-3 with various kinases in S2 Schneider cells promoted a phosphorylation of calponin-3 by Syk, but also by the Tec family kinase Btk.

SIGNOR-280196

P67775

Q9H0H5

1

dephosphorylation

down-regulates

0.303

We report here that (i) mgcracgap is phosphorylated by aurora b and cdk1, (ii) pp2a dephosphorylates aurora b and cdk1 phosphorylated sites and (iii) inhibition of pp2a abrogates mgcracgap/ect2 interaction. Therefore, pp2a may regulate cytokinesis by dephosphorylating mgcracgap and its interacting partners.

SIGNOR-160398

P10147

Q92794

0

transcriptional regulation

up-regulates quantity by expression

0.2

We further demonstrate that the histone acetyltransferase, MOZ, can activate the MIP-1a promoter in T-cells and that this activation is largely dependent upon the proximal RUNX site. Moreover, we show that co-expression of MOZ and RUNX1 can activate the MIP-1a promoter.

SIGNOR-251726

P54259

P45983

0

phosphorylation

down-regulates activity

0.376

Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-jun nh2-terminal kinase. serine 734 of the drpla protein is a phospho-acceptor site by jnk. The phosphorylation may be coupled to the activation of a protease. The molecular size of drpla protein detected in the rat brain with the specific phosphopeptide antibody was 150_kda, which was slightly smaller than that expected from the sequence and the results with the human protein. The phosphorylated forms of ha-tagged human drpla gradually disappeared after osmotic treatment,

SIGNOR-102398

Q00535

Q9GZM8

1

phosphorylation

up-regulates activity

0.772

Three specific phosphorylation sites (Ser198, Thr219 and Ser231) and two weak phosphorylation sites (Ser242 and Thr245) for CDK5/p35 are located in this region of NUDEL | Each single or double mutant compromised,and the triple mutant completely eliminated, interaction with 14-3-3ε. | 14-3-3ε sustains NUDEL phosphorylation and protects it from phosphatase.e dynein motor function.

SIGNOR-250676

P51812

P49840

1

phosphorylation

down-regulates activity

0.265

P90-rsk and akt may promote rapid phosphorylation/inactivation of glycogen synthase kinase 3 in chemoattractant-stimulated neutrophils. These reactions were monitored with a phosphospecific antibody that only recognized the alpha- or beta-isoforms of GSK-3 when these proteins were phosphorylated on serine residues 21 and 9, respectively.

SIGNOR-110827

P17252

P17812

1

phosphorylation

down-regulates

0.2

These data indicated that protein kinase c phosphorylation at ser(462) stimulates human ctp synthetase 1 activity, whereas phosphorylation at thr(455) inhibits activity.

SIGNOR-154621

P27361

Q9BVJ7

0

dephosphorylation

down-regulates activity

0.31

In particular, DUSP23 can dephosphorylate and inactivate MAPK3 ( xref ).|In particular, DUSP23 can dephosphorylate and inactivate MAPK3.

SIGNOR-277103

Q6PML9

P49757

1

ubiquitination

down-regulates quantity by destabilization

0.2

Lnx functions as a ring type e3 ubiquitin ligase that targets the cell fate determinant numb for ubiquitin-dependent degradation.

SIGNOR-113704

Q13309

P48735

1

ubiquitination

down-regulates quantity by destabilization

0.2

During the cell cycle S phase, Cyclin A-CDK2 phosphorylates IDH1 on its Threonine 157 residue (Threonine 197 in IDH2) to facilitate its recognition and ubiquitination by Skp2 E3 ubiquitin, followed by degradation through 26S proteasome

SIGNOR-267626

P48454

Q92934

1

dephosphorylation

up-regulates activity

0.399

Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD|Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis.

SIGNOR-248529

P28749

P67775

0

dephosphorylation

up-regulates

0.623

Pocket protein family consists of the retinoblastoma tumor suppressor protein (prb) and the functionally and structurally related proteins p107 and p130./dephosphorylation of p130 and p107 in cell extracts is inhibited by concentrations of okadaic acid known to inhibit pp2a, but not pp1. Finally, the pp2a catalytic subunit pp2a/c) specifically interacts with both p130 and p107 / the cell cycle repressor activity of pocket proteins is inactivated by cdk mediated phosphorylation.

SIGNOR-129749

Q13976

P78347

1

phosphorylation

up-regulates

0.569

G-kinase phosphorylated tfii-i in vitro and in vivo on ser(371) and ser(743) outside of the interaction domain. G-kinase strongly enhanced tfii-i transactivation of a serum-response element-containing promoter in cos7 cells

SIGNOR-89849

P42772

Q9HCX3

0

transcriptional regulation

down-regulates quantity by repression

0.28

Finally, we show that ZNF304 also directs transcriptional silencing of INK4-ARF in human embryonic stem cells.

SIGNOR-266099

P45983

P85298

1

phosphorylation

up-regulates activity

0.327

Furthermore, we identify that BPGAP1 (a BCH domain-containing, Cdc42GAP-like Rho GTPase-activating protein) promotes MEK partner 1 (MP1)-induced ERK activation on late endosome through scaffolding MP1/MEK1 complex. This regulatory function requires phosphorylation of BPGAP1 by JNK at its C terminal tail (Ser424) to unlock its autoinhibitory conformation.

SIGNOR-275550

Q07955

P49759

0

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

Q14653

Q9UHD2

0

phosphorylation

up-regulates activity

0.822

Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404.

SIGNOR-178420

Q00535

P46527

1

phosphorylation

down-regulates activity

0.643

CDK5 knockdown in HEY cells significantly prolonged the half-life of TP53 and p27 Kip1 proteins (XREF_FIG).|During neural stem cell differentiation, CDK5 can phosphorylate p27 at Thr187 and at Ser10, promoting neurite outgrowth as neurons differentiate .

SIGNOR-279681

P08047

Q92820

1

transcriptional regulation

up-regulates quantity by expression

0.2

Overexpression of Sp1 led to enhanced GGH promoter activity and GGH mRNA expression in allele-specific manners. These findings suggested that Sp1 acted as a positive regulator of human GGH transcription through the rs3758149 polymorphism in CEM/C1 cells.

SIGNOR-261350

P31749

P78362

1

phosphorylation

up-regulates

0.465

Here we show that srpk2, a protein kinase specific for the serine/arginine (sr) family of splicing factors, triggers cell cycle progression in neurons and induces apoptosis through regulation of nuclear cyclin d1. Akt phosphorylates srpk2 on thr-492 and promotes its nuclear translocation leading to cyclin d1 up-regulation, cell cycle reentry, and neuronal apoptosis.

SIGNOR-186760

P06493

P23769

1

phosphorylation

down-regulates quantity by destabilization

0.355

GATA2 contains a cell division control protein 4 (Cdc4) phosphodegron (CPD), a consensus motif for ubiquitylation by Fbw7, which includes Thr(176). Ectopic expression of Fbw7 destabilized GATA2 and promoted its proteasomal degradation. Substitution of threonine 176 to alanine in GATA2 inhibited binding with Fbw7, and the ubiquitylation and degradation of GATA2 by Fbw7 was suppressed. The CPD kinase, which mediates the phosphorylation of Thr(176), was cyclin B-cyclin-dependent kinase 1 (CDK1).

SIGNOR-276884

Q15831

P60484

1

phosphorylation

down-regulates activity

0.604

The C-terminal tail of PTEN is also the target of mutations in tumors. As mentioned, this region contains the main phosphorylation sites mapped to residues Ser362, Thr366, Ser370, Ser380, Thr382, Thr383, and Ser385, and the kinases involved are casein kinase 2 (CK2), GSK3_, LKB1, and MAST.84,97-101 The phosphorylation of the tail has been shown to enhance PTEN stability but at the same time decrease its phosphatase activity

SIGNOR-161118

Q12879

P06241

0

phosphorylation

up-regulates activity

0.734

To gain further insight into the roles of Src and Fyn in the phosphorylation and regulation of the NMDA receptor, we have characterized the tyrosine phosphorylation of NR2A and NR2B by exogenous Src and FynIn the case of NR2A, three potential tyrosine phosphorylation sites have been proposed: Tyr1105, Tyr1267 and Tyr1387 (Zheng et al. 1998; Bi et al. 2000), all of which are similarly located in the C-terminal, cytoplasmic domain.

SIGNOR-247151

P28329

P17252

0

phosphorylation

up-regulates

0.383

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

SIGNOR-129264

Q12955

Q14576

0

post transcriptional regulation

down-regulates quantity

0.25

NElavl (composed of Elavl2, Elavl3, and Elavl4) proteins are the RNA-binding proteins that is specifically expressed in neurons, regulate the alternative splicing of target RNAs, and promote neuronal differentiation and maturation. Here, we found that the alternative splicing of AnkyrinG exon 34 was misregulated in the cerebella of Elavl3-/- mice. AnkyrinG is an essential factor for the formation of neuronal polarity and is required for normal neuronal functions.

SIGNOR-266861

P33778

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.

SIGNOR-265385

P08047

O00141

0

phosphorylation

up-regulates activity

0.265

In fact, SGK1 activates and phosphorylates SP1 on serine 59, a regulator of nucleocytoplasmic trafficking related genes .|In fact, SGK1 activates and phosphorylates SP1 on serine 59, a regulator of nucleocytoplasmic trafficking-related genes xref .

SIGNOR-279246

P11678

P12724

1

post translational modification

up-regulates activity

0.477

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-261705

Q00987

P06400

1

ubiquitination

down-regulates quantity by destabilization

0.667

In this study, we found that Mdm2, a ubiquitin ligase for p53, promoted ubiquitin-dependent degradation of pRB

SIGNOR-278530

Q8WUI4

O43318

0

phosphorylation

down-regulates

0.2

We further show that emk and c-tak1 phosphorylate class iia hdacs on one of their multiple 14-3-3 binding sites and alter their subcellular localization and repressive function

SIGNOR-149579

P49841

Q12888

1

phosphorylation

up-regulates activity

0.283

Based on these observations, we hypothesized that the IR induced GSK3beta nuclear translocation may activate 53BP1 via phosphorylation at the S/T-Q motif.|Importantly, our in vivo and in vitro data clearly indicated that GSK3\u03b2 induced the phosphorylation of 53BP1 at the Ser166 site.

SIGNOR-278226

Q12857

P54756

1

transcriptional regulation

up-regulates quantity

0.2

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268895

P09769

P43405

1

phosphorylation

up-regulates activity

0.594

Fgr associates with Fc\u03b5RI and phosphorylates Syk in antigen-stimulated mast cells.|The overexpression of Fgr stimulates Syk, Syk dependent signaling molecules, and degranulation in RBL-2H3 cells and BMMCs.

SIGNOR-279332

P51812

P04637

1

phosphorylation

up-regulates activity

0.336

Here we show that ribosomal S6 kinase 2 (RSK2) activates and phosphorylates p53 (Ser15) in vitro and in vivo and colocalizes with p53 in the nucleus.

SIGNOR-279567

P60484

Q13285

1

dephosphorylation

down-regulates activity

0.256

The fact that SF-1 and PIP3 is robustly dephosphorylated by PTEN, yet SF-1 and PIP2 is resistant to phosphorylation by p110 PI3-kinases, suggests that nuclear proteins like SF-1 can help decouple PTEN signaling in the nucleus from p110 signaling.|We also showed that PTEN can dephosphorylate the SF-1 and PIP3 product of the IPMK reaction, and that PTEN inhibits SF-1 transcriptional activity.

SIGNOR-277117

Q9NPD5

P20823

0

transcriptional regulation

up-regulates quantity by expression

0.251

Farnesoid X receptor, hepatocyte nuclear factors 1alpha and 3beta are essential for transcriptional activation of the liver-specific organic anion transporter-2 gene.|This study demonstrated that the transcription of the LST-2 gene is regulated by three transcription factors, FXR, HNF1alpha, and HNF3beta.

SIGNOR-268988

Q99576

Q53ET0

0

transcriptional regulation

up-regulates quantity

0.2

CRTC2 knockdown attenuates glucocorticoid-responsive GILZ mRNA expression in HeLa cells

SIGNOR-256109

O15530

P53350

1

phosphorylation

up-regulates activity

0.2

Here, we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces MYC phosphorylation and protein accumulation. We show that PDK1-PLK1-MYC signaling is critical for cancer cell growth and survival, and small-molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting of MYC dependency

SIGNOR-243519

Q9BPU6

P49841

0

phosphorylation

up-regulates activity

0.431

The T516 phosphorylation was achieved by the glycogen synthase kinase-3beta (GSK-3beta), which can phosphorylate the wildtype protein but not the non-phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin-binding property of CRMP5. Therefore, CRMP5-induced growth inhibition is dependent on T516 phosphorylation through the GSK-3beta pathway.

SIGNOR-264835

P31269

P06748

0

transcriptional regulation

down-regulates quantity by repression

0.352

In AML cells, NPM1 mutations result in abnormal cytoplasmic localization of the mutant protein (NPM1c); however, it is unknown whether NPM1c is required to maintain the leukemic state. Here, we show that loss of NPM1c from the cytoplasm, either through nuclear relocalization or targeted degradation, results in immediate downregulation of homeobox (HOX) genes followed by differentiation.

SIGNOR-260138

Q00526

Q12800

1

phosphorylation

down-regulates

0.264

In vitro, lsf is phosphorylated by cyclin e/cyclin-dependent kinase 2 (cdk2), cyclin c/cdk2, and cyclin c/cdk3, predominantly on s309. Phosphorylation by cyclin c/cyclin-dependent kinase 2 following mitogenic stimulation of murine fibroblasts inhibits transcriptional activity of lsf during g1 progression

SIGNOR-184164

P13349

P17661

1

transcriptional regulation

up-regulates quantity by expression

0.241

Desmin, the muscle specific intermediate filament (IF) protein, is expressed at low levels in myoblasts and at the onset of differentiation its expression increases several fold. In an effort to explore the mechanism involved in the tissue-specific and developmentally regulated expression of desmin, we have isolated the mouse desmin gene.Co-transfection of myoD, myogenin, MRF4 and Myf5, with the desmin-CAT construct into 10T-1/2 cells demonstrated that all these factors could transactivate desmin gene expression

SIGNOR-241494

Q13315

O43684

1

phosphorylation

up-regulates activity

0.312

Taken together, we highlight the functional significance of the crosstalk between the kinetochore-oriented signal and double-strand break repair pathways via ATM phosphorylation of Bub3 on Ser135.

SIGNOR-277582

Q99717

Q9HCE7

0

ubiquitination

down-regulates

0.769

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

SIGNOR-195663

P36956

Q5VTR2

0

ubiquitination

down-regulates activity

0.425

Here, we reveal that RNF20-induced SREBP1c ubiquitination down-regulates hepatic lipogenic activity upon PKA activation.|Overexpression of RNF20 represses SREBP1c activity, leading to a decrease in the expression of lipogenic genes.

SIGNOR-278643

P41182

Q9BZL6

0

phosphorylation

down-regulates activity

0.2

Prkd2 directly binds to Bcl6 and Prkd2-dependent phosphorylation of Bcl6 is necessary to constrain Bcl6 to the cytoplasm, thereby limiting TFH development.

SIGNOR-279651

Q09472

P04637

1

polyubiquitination

down-regulates quantity by destabilization

0.912

P53 is stabilized by the binding of p300 to the oncoprotein E1A, suggesting that p300 regulates p53 degradation. Purified p300 exhibited intrinsic ubiquitin ligase activity that was inhibited by E1A. In vitro, p300 with MDM2 catalyzed p53 polyubiquitination, whereas MDM2 catalyzed p53 monoubiquitination. E1A expression caused a decrease in polyubiquitinated but not monoubiquitinated p53 in cells. Thus, generation of the polyubiquitinated forms of p53 that are targeted for proteasome degradation requires the intrinsic ubiquitin ligase activities of MDM2 and p300.

SIGNOR-271418

O00429

Q00535

0

phosphorylation

up-regulates activity

0.464

CDK5 activates DRP1 in BTICs.|To determine if CDK5 could directly phosphorylate DRP1, we performed an in vitro kinase assay with CDK5, its regulatory partner p25 and GST-DRP1 (wild type or S616A mutant) and found that CDK5 directly phosphorylates DRP1 on the S616 site (Fig. 7d).

SIGNOR-278275

Q13501

Q99759

0

phosphorylation

up-regulates activity

0.556

MEKK3 overexpression, but not that of a kinase dead mutant, was able to induce the phosphorylation of p62 at T269 and S272 (XREF_FIG), which correlated with mTORC1 activation (XREF_FIG), suggesting that MEKK3 could be a bona fide regulator of p62 phosphorylation and mTORC1 activity.

SIGNOR-279532

O96017

P30304

1

phosphorylation

down-regulates quantity by destabilization

0.843

We show that IR-induced destruction of Cdc25A requires both ATM and the Chk2-mediated phosphorylation of Cdc25A on serine 123.

SIGNOR-106808

P46937

O75385

0

phosphorylation

up-regulates quantity by stabilization

0.2

Mechanistically, hypoxia stimulates ULK1 to translocate into nucleus, where it interacts with and phosphorylates yes-associated protein (YAP) at Ser227, resulting in YAP stabilization through blockade of ubiquitin-proteasome system (UPS), which in turn facilitates PKM2 transcription, glycolysis, cell proliferation in vitro as well as PDAC growth in mice.

SIGNOR-277570

P12931

Q9H2X6

1

phosphorylation

up-regulates activity

0.307

Using mass spectrometry we identified 9 Src-mediated Tyr-phosphorylation sites within HIPK2, 5 of them positioned in the kinase domain.|We demonstrate that ectopic expression of Src increases the half-life of HIPK2 by interfering with Siah-1-mediated HIPK2 degradation.

SIGNOR-278989

P46531

Q16566

0

phosphorylation

up-regulates quantity by stabilization

0.36

In summary, we have found that phosphorylation of Notch1-IC by CaMKIV inhibits the proteasomal degradation of Notch1-IC through Fbw7 ( Fig.\u00a07 ).

SIGNOR-279596

P10276

P31749

0

phosphorylation

down-regulates

0.602

We report that akt, which is constitutively activated in nsclc cells, phosphorylates raralpha and inhibits its transactivation. / mutation of ser96 to alanine abrogated the suppressive effect of akt.

SIGNOR-252489

Q99759

O14920

1

phosphorylation

up-regulates activity

0.569

Genetic analysis showed that MEKK3, which is thought to activate IKK2 through phosphorylation (Yang et al., 2001), is necessary for TNF-alpha-induced NF-kappaB activation.|Our results also suggest that IKK2 is phosphorylated on S177 and S181 on its activation loop by MEKK3.

SIGNOR-279468

Q7KZI7

Q6WKZ4

1

phosphorylation

up-regulates quantity

0.341

We have now found that MARK2 phosphorylates Rab11-FIP1B/C at serine 234 in a consensus site similar to that previously identified in Rab11-FIP2.

SIGNOR-273676

P46695

P28482

0

phosphorylation

up-regulates

0.552

Upon phosphorylation by erks, iex-1 acquires the ability to inhibit cell death induced by various stimuli. In turn, iex-1 potentiates erk activation in response to various growth factors.

SIGNOR-93740

P68400

P01106

1

phosphorylation

down-regulates quantity by destabilization

0.504

Together, our findings provide evidence for CK1α-mediated destruction of c-Myc and identify c-Myc S252 as a crucial CK1α phosphorylation site for c-Myc degradation.

SIGNOR-276388

Q14493

P84243

1

translation regulation

up-regulates quantity by expression

0.2

Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.

SIGNOR-265418

Q99638

Q9UKI8

0

phosphorylation

up-regulates

0.448

Tlk1b phosphorylates hrad9 at s328 after the induction of dsb, occupancy of rad9 adjacent to the break increased during repair while that of asf1 decreased, and the effect was more pronounced in tlk1b-overexpressing cells. We propose that following genotoxic stress, tlk1/1b is first recruited to the dsb in a complex with rad9. It then exchanges with asf1 to promote nucleosomes eviction at the dsb and access of the repair machinery to unencumbered dna.

SIGNOR-181748

Q15417

P06241

0

phosphorylation

down-regulates activity

0.333

We identify, for the first time, tyrosine-phosphorylated calponin h3 within COS 7 cells, before and after their transfection with the pSV vector containing cDNA encoding the cytoplasmic, Src-related, tyrosine kinase, Fyn. we have localized the tyrosines phosphorylated without actin to Tyr261 in calponin h3 and to Tyr261 and Tyr182 in calponin h1. Tyrosine phosphorylation of calponins inhibits their binding to F-actin

SIGNOR-251159

P06239

P24666

1

phosphorylation

up-regulates activity

0.354

In co-transfected COS cells, Lck and Fyn caused phosphorylation of LMPTP. Most of the phosphate was located at Tyr-131, and some was also located at Tyr-132. Site-directed mutagenesis showed that Tyr-131 is important for the catalytic activity of LMPTP, and that thiophosphorylation of Tyr-131, and to a lesser degree Tyr-132, is responsible for the activation.

SIGNOR-251367

P04792

Q13237

0

phosphorylation

down-regulates

0.2

Purified pkg isoforms ia, ib, and ii all caused incorporation of phosphate in recombinant hsp27 at ser-78, ser-82, and thr-143, but not ser-15.These Studies indicate that hsp27 is a genuine substrate for pkg and that pkg may mediate inhibition of platelet aggregation through phosphorylation of hsp27 and subsequent prevent of actin polymerization

SIGNOR-186947

O00429

Q13546

0

phosphorylation

up-regulates activity

0.51

RIPK1 also activates DRP1 by phosphorylating DRP1 at Ser616 in a RIPK3-dependent fashion independent of MLKL.

SIGNOR-280104

Q06330

P38936

1

transcriptional regulation

up-regulates quantity by expression

0.307

Induction of the p21WAF1/Cip1 gene by Notch 1 activation in differentiating keratinocytes is associated with direct targeting of the RBP-J_ protein to the p21 promoter.

SIGNOR-252032

Q92630

P10070

1

phosphorylation

down-regulates quantity by destabilization

0.3

DYRK2 directly phosphorylated Gli2 sequences and resulted in the loss of coexpressed GLI proteins, indicating that DYRK2 acts by inducing the phosphorylation and degradation of GLI proteins via the ubiquitin and proteasome pathway.

SIGNOR-279034

P29353

P23470

0

dephosphorylation

down-regulates activity

0.2

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254724

Q92530

O95271

0

ADP-ribosylation

down-regulates quantity by destabilization

0.501

We identify the ADP-ribosyltransferase tankyrase (TNKS) and the 19S assembly chaperones dp27 and dS5b as direct binding partners of the proteasome regulator PI31. TNKS-mediated ADP-ribosylation of PI31 drastically reduces its affinity for 20S proteasome alpha subunits to relieve 20S repression by PI31.

SIGNOR-263387

Q9Y572

Q13490

0

polyubiquitination

up-regulates activity

0.677

CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.

SIGNOR-272711

P06493

P23443

1

phosphorylation

up-regulates

0.384

Interestingly, phosphorylation at several ser/thr residues within the c-terminal autoinhibitory tail appears to either activate or inhibit s6k1, depending on the cell cycle phase. phosphorylation of those residues (featured by the thr-421/ser-424 site) during mitosis pursued by cdk1 inactivates s6k1 we then assessed the phosphorylation status of the mitosis-specific inhibitory residue of s6k1, thr-421/ser-424, which is targeted by mitotic cdk1.

SIGNOR-111507

Q13177

P01106

1

phosphorylation

down-regulates activity

0.649

Here we demonstrate that Pak2 phosphorylates Myc at three sites (T358, S373, and T400) and affects Myc functions both in vitro and in vivo.

SIGNOR-278489

P06241

Q9ULL1

1

phosphorylation

up-regulates activity

0.2

We also show that this activation of PLEKHG1 by FYN requires interaction between these two proteins and FYN-induced tyrosine phosphorylation of PLEKHG1 .|We also show that this activation of PLEKHG1 by FYN requires interaction between these two proteins and FYN-induced tyrosine phosphorylation of PLEKHG1.

SIGNOR-279988

Q9NWT8

O14965

0

phosphorylation

up-regulates quantity by stabilization

0.681

AIP is phosphorylated on Serine 70 by Aurora‐A but not Aurora‐B and expression of phosphorylation mimic mutant of AIP results in prolonged protein stability compared to unphosphorylatable mutant. Phosphorylation of AIP Prolongs its Protein Stability

SIGNOR-262648

Q96PY5

P06493

0

phosphorylation

up-regulates activity

0.2

In this study we have identified the formin FMNL2 as a novel substrate for CDK1 that plays a role in maintaining adhesion complexes and facilitates cell cycle–dependent changes in adhesion complexes. Knockdown of FMNL2 or expression of a nonphosphorylatable S1016A mutant resulted in the loss of adhesion complexes and stress fibers within the cell body, with peripheral structures being maintained.

SIGNOR-273555

P28482

Q08493

1

phosphorylation

down-regulates

0.256

The short-form pde4b2 isoenzyme was activated by erk2 phosphorylation. sub-family selective actions in the ability of erk2 map kinase to phosphorylate and regulate the activity of pde4 cyclic amp-specific phosphodiesterases

SIGNOR-83187

Q15672

P45983

0

phosphorylation

up-regulates

0.308

Phosphorylation of serine 68 of twist1 by mapks stabilizes twist1 protein and promotes breast cancer cell invasiveness.

SIGNOR-173417

P24928

O00308

0

ubiquitination

down-regulates quantity

0.387

WWP2 ubiquitylates RNA polymerase II for DNA-PK-dependent transcription arrest and repair at DNA breaks|In response to DSBs, WWP2 targets the RNAPII subunit RPB1 for K48-linked ubiquitylation, thereby driving DNA-PK- and proteasome-dependent eviction of RNAPII.

SIGNOR-268851

P04626

O14672

0

cleavage

up-regulates activity

0.344

The ADAM proteases are best known for their role in shedding the extracellular domain of transmembrane proteins. Among the transmembrane proteins shed by ADAM10 are notch, HER2, E-cadherin, CD44, L1 and the EGFR ligands, EGF and betacellulin.

SIGNOR-259845

Q14938

O75093

1

transcriptional regulation

up-regulates quantity

0.2

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268906

P23467

P28482

1

dephosphorylation

down-regulates

0.382

Expression of rptp-beta inhibits both mek1/2 and erk1/2 phosphorylation.

SIGNOR-173000

Q9H1D0

P18031

0

dephosphorylation

down-regulates activity

0.631

In HEK293 cells, transfected with the Ca2+ channel protein TRPV6, Ca2+ influx is increased and TRPV6 is tyrosine phosphorylated following addition of the tyrosine phosphatase inhibitor|PTP1B interacts with the N-terminal domain of TRPV6 within a region of amino acids 1-191 as shown by co-immunoprecipitation, bimolecular fluorescence complementation and the yeast 2-hybrid system. Point mutation of both tyrosines 161 and 162 in the TRPV6 protein abolishes the DMHV-effect on Ca2+ influx and tyrosine phosphorylation by Src. Single mutations of Y161 or Y162 shows that each of both tyrosines alone is sufficient for the DMHV-effect. We conclude that phosphorylation/dephosphorylation of tyrosines in position 161 and 162 is essential for regulation of Ca2+ influx through TRPV6 Ca2+ channels in HEK293 cells.

SIGNOR-248433

Q9Y6A5

O14965

0

phosphorylation

up-regulates activity

0.937

We show that this conserved serine on human TACC3 (Ser(558)) is also phosphorylated by Aurora A. Moreover, phosphorylation of TACC3 by Aurora A in human cells is essential for its proper localization to centrosomes and proximal mitotic spindles. Inhibition of Aurora A with the selective small molecule inhibitor MLN8054 in cultured human tumor cells resulted in mislocalization of TACC3 away from mitotic spindles in a concentration-dependent manner.

SIGNOR-262655

Q05655

Q9UQ13

1

phosphorylation

down-regulates quantity by destabilization

0.2

PKCalpha/delta phosphorylate Sur8 at Thr-71 and Ser-297, respectively. This phosphorylation is essential for polyubiquitin-dependent degradation of Sur8.

SIGNOR-275565

P08473

P68400

0

phosphorylation

down-regulates

0.323

The cytoplasmic n-terminal domain of nep interacts with the phosphatase and tensin homologue deleted on chromosome 10 (pten) thereby regulating intracellular signaling via akt. Ser 6 is efficiently phosphorylated by protein kinase ck2. The phosphorylation of the cytoplasmic domain of nep inhibits its interaction with pten.

SIGNOR-168673

P21731-2

P25098

0

phosphorylation

down-regulates activity

0.2

These data suggest a model whereby agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling, profoundly desensitizing signalling, and promotes beta-arrestin association and, in turn, facilitates TPbeta internalization.

SIGNOR-274088

P23528

Q76I76

0

dephosphorylation

up-regulates activity

0.732

Differential activities, subcellular distribution and tissue expression patterns of three members of Slingshot family phosphatases that dephosphorylate cofilin.|Cofilin, a key regulator of actin filament dynamics, is inactivated by phosphorylation at Ser-3 by LIM-kinases and is reactivated by dephosphorylation by a family of protein phosphatases, termed Slingshot (SSH).

SIGNOR-248733

P49815

O15111

0

phosphorylation

down-regulates

0.296

Insulin activation of mtor requires akt in a manner that involves ikkalpha, preferentially to ikkbeta, and tsc2 phosphorylation

SIGNOR-178664

P28482

O15027

1

phosphorylation

up-regulates activity

0.352

Recombinant active ERK2 also phosphorylated Sec16 (XREF_FIG).

SIGNOR-280022

Q5SQI0

Q9BQE3

1

acetylation

up-regulates quantity by stabilization

0.246

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

SIGNOR-272247

P17612

P13224

1

phosphorylation

down-regulates activity

0.312

Platelet glycoprotein Ib beta is phosphorylated on serine 166 by cyclic AMP-dependent protein kinase. phosphorylation of this residue may contribute to the inhibitory actions of cyclic AMP by inhibiting collagen-induced polymerization of actin.

SIGNOR-249986

Q8WU20

P21802

0

phosphorylation

up-regulates activity

0.777

In this report, we demonstrate that FGF stimulation induces tyrosine phosphorylation of a novel lipid anchored docking protein, termed FRS2, that forms a complex with Grb2/Sos, thus linking FGF-receptor activation to the Ras/MAPK signaling pathway.

SIGNOR-236950

P62136

Q02447

1

dephosphorylation

down-regulates activity

0.2

Transcription factors Sp1 and Sp3 activate alpha-ENaC2 transcription through a GC-rich element (Sp1-binding site) in the promoter. Sp1 and Sp3 are essential for alpha-ENaC2 transcription in lung epithelial cells and that dephosphorylation of the Sp transcription factors by PP1 suppresses alpha-ENaC2 expression.

SIGNOR-251953

Q15019

P68400

0

phosphorylation

down-regulates

0.2

Here we show that human septin 2 is phosphorylated in vivo at ser218 by casein kinase ii. Septin 2 binds and hydrolyses gtp. The purified protein has the capacity to polymerize into long filaments when loaded with gtp or gdp. Moreover, we show that the endogenous protein in hela cells, like that produced in insect cells, is phosphorylated by casein kinase ii and that this phosphorylation alters nucleotide binding.

SIGNOR-148010

Q13315

Q9BW19

1

phosphorylation

up-regulates quantity by stabilization

0.2

ATM and ATR kinases phosphorylate KIFC1-S26 during DNA-damage conditions.KIFC1 was stabilized upon phosphorylation and thus promoted centrosome clustering, CIN, and tumor recurrence both in vivo and in vitro.

SIGNOR-277295