GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q13224	P68400	0	phosphorylation	down-regulates	0.324	Here we show that casein kinase ii (ck2) phosphorylates the serine residue (ser1480) within the c-terminal pdz ligand (iesdv) of the nr2b subunit of nmdar in vitro and in vivo. Phosphorylation of ser1480 disrupts the interaction of nr2b with the pdz domains of psd-95 and sap102 and decreases surface nr2b expression in neurons.	SIGNOR-130336
Q00535	Q96SB3	1	phosphorylation	down-regulates quantity	0.396	CDK5 decreased the expression of both spinophilin (30%) and neurabin (64%).\|This suggests that CDK5 phosphorylation of spinophilin at Ser17 is not responsible for the CDK5 dependent increase in the spinophilin and PP1 association.	SIGNOR-279453
Q02078	P23409	1	transcriptional regulation	up-regulates quantity by expression	0.589	Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis.	SIGNOR-238709
P50539	P14635	1	transcriptional regulation	down-regulates quantity by repression	0.266	Mxi1 inhibits the proliferation of U87 glioma cells through down-regulation of cyclin B1 gene expression \| Mxi1 inhibits the promoter activity of the cyclin B1 gene.	SIGNOR-266064
P06400	Q00535	0	phosphorylation	down-regulates	0.336	Phosphorylation was observed 6 hours after p25 induction and was abolished in the presence of a cdk5 inhibitor, roscovitine, which does not inhibit the usual rb cyclin-d kinases cdk4 and cdk6. Furthermore, analyses of levels and subcellular localization of cdk-related cyclins did not reveal any change following cdk5 activation, arguing for a direct effect of cdk5 activity on rb protein. Rb phosphorylation was visualized using phosphorylation-dependent antibodies (p-rbser795 and p-rbser807/811).	SIGNOR-134468
P25098	Q99835	1	phosphorylation	up-regulates	0.2	We find that two molecules interact with mammalian smo in an activation-dependent manner: g protein-coupled receptor kinase 2 (grk2) leads to phosphorylation of smo, and beta-arrestin 2 fused to green fluorescent protein interacts with smo. Ck1a, grk2, and another still-unidentified protein kinase phosphorylate the c-tail of mammalian smo in the presence of hh proteins	SIGNOR-174539
P43405	Q8N6F7	1	phosphorylation	up-regulates activity	0.356	Herein, we demonstrate phosphorylation of HGAL by Syk and Lyn kinases at tyrosines Y80, Y86, Y106Y107, Y128, and Y148. Y148 (in black) was already phosphorylated before the addition of kinases. We demonstrate that Grb2 facilitates HGAL and Syk binding following BCR stimulation but does not affect the HGAL-mediated increase in Syk kinase activity. Previous studies showed that Grb2 inhibits BCR signaling by decreasing the activation of Syk by Lyn.11 Thus, while HGAL and Grb2 oppositely affect Syk kinase activity, this is not due to direct Grb2 effects on HGAL-mediated Syk kinase activation.	SIGNOR-273570
P04637	O95831	1	transcriptional regulation	up-regulates quantity by expression	0.351	P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway.	SIGNOR-267462
P05771	O60346	0	dephosphorylation	down-regulates quantity	0.341	Here we show that the two PHLPP isoforms, PHLPP1 and PHLPP2, also dephosphorylate the hydrophobic motif on PKC betaII, an event that shunts PKC to the detergent-insoluble fraction, effectively terminating its life cycle	SIGNOR-237047
Q00987	Q93009	0	deubiquitination	up-regulates	0.77	Subsequently, hausp was shown to deubiquitinate mdm2 and mdmx, thereby stabilizing these proteins.	SIGNOR-139450
P22694	P08138	1	phosphorylation	up-regulates	0.625	Pka phosphorylates the p75 receptor and regulates its localization to lipid rafts. activation of camp?PKA Is required for translocation of p75ntr to lipid rafts, and for biochemical and biological activities of p75ntr, such as inactivation of rho and the neurite outgrowth.	SIGNOR-99755
P25098	Q05655	0	phosphorylation	up-regulates activity	0.2	Phosphorylation of GRK2 by protein kinase C abolishes its inhibition by calmodulin. In vitro, GRK2 was preferentially phosphorylated by PKC isoforms alpha, gamma, and delta. Two-dimensional peptide mapping of PKCalpha-phosphorylated GRK2 showed a single site of phosphorylation, which was identified as serine 29 by HPLC-MS. A S29A mutant of GRK2 was not phosphorylated by PKC in vitro and showed no phorbol ester-stimulated phosphorylation when transfected into human embryonic kidney (HEK)293 cells.	SIGNOR-249059
O94788	Q05086	0	ubiquitination	down-regulates quantity by destabilization	0.2	Hyperactivity of E3 ubiquitin (Ub) ligase UBE3A, stemming from 15q11-q13 copy number variations, accounts for 1%-3% of ASD cases worldwide, but the underlying mechanisms remain incompletely characterized. Here we report that the functionality of ALDH1A2, the rate-limiting enzyme of retinoic acid (RA) synthesis, is negatively regulated by UBE3A in a ubiquitylation-dependent manner.	SIGNOR-265135
P24941	P49459	1	phosphorylation	up-regulates	0.374	Hhr6a is phosphorylated in vitro by cdk-1 and -2 on ser120, a residue conserved in all hhr6a homologues, resulting in a 4-fold increase in its ubiquitin-conjugating activity.	SIGNOR-116508
Q9Y6H5	O60260	0	ubiquitination	down-regulates quantity by destabilization	0.2	Here we show that parkin interacts with and ubiquitinates the alpha-synuclein-interacting protein, synphilin-1.	SIGNOR-278550
Q38SD2	P30622	1	phosphorylation	up-regulates activity	0.398	LRRK1 phosphorylates CLIP-170 at Thr1384, located in its C-terminal zinc knuckle motif, and this promotes the association of CLIP-170 with dynein-dynactin complexes.	SIGNOR-275469
P18848	P05198	0	transcriptional regulation	down-regulates quantity	0.64	ER stress, viral infection, and other cellular stress signals activate PERK, PKR, HRI, and GCN2 kinases that converge on phosphorylation of eIF2alpha, the core of ISR. This leads to global attenuation of Cap Âdependent translation while concomitantly initiates the preferential translation of ISR Âspecific mRNAs, such as ATF4. ATF4 is the main effector of the ISR. eIF2alpha phosphorylation causes a reduction in global protein synthesis while allowing the translation of selected genes including activating transcription factor 4 (ATF4), aiding cell survival and recovery	SIGNOR-260169
Q92949	O75602	1	transcriptional regulation	up-regulates quantity by expression	0.447	FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).	SIGNOR-266935
P78527	P52945	1	phosphorylation	down-regulates quantity by destabilization	0.307	The interaction of PDX-1 with Ku subunits and its phosphorylation on threonine 11 by the DNA-PK appear to be implicated in its degradation by the proteosome.	SIGNOR-225542
O14965	Q8NHV4	1	phosphorylation	up-regulates activity	0.557	Microtubule nucleation during central spindle assembly requires NEDD1 phosphorylation on serine 405 by Aurora A\| In the absence of Aurora A, the HURP (also known as DLGAP5) and NEDD1 proteins that are involved in nucleation of microtubules fail to concentrate in the midzone.	SIGNOR-272965
P00519	O00401	1	phosphorylation	up-regulates activity	0.55	Abl phosphorylates N-WASP on tyrosines 175 and 256. Phosphorylation at this site stabilizes the active conformation of N-WASP, resulting in comet tail elongation.	SIGNOR-251437
P60852	Q5JUK2	0	transcriptional regulation	up-regulates quantity by expression	0.2	Cotransfection of a mouse Sohlh1 expression vector with E box-containing promoter regions of mouse Lhx8, Zp1, and Zp3 fused to luciferase resulted in significant transactivation . Mutation of the E box sequences abolished SOHLH1-dependent stimulation. Thus, Lhx8, Zp1, and Zp3 are likely direct downstream target genes of SOHLH1 through the E box elements in their promoters.	SIGNOR-266077
P49841	Q6IA17	1	phosphorylation	down-regulates quantity by destabilization	0.2	Activation of GSK3beta promotes Sigirr degradation in the proteasome .\|Taken together, IL-37-induced Sigirr internalization is dependent on phosphorylation of Sigirr in T372 residue by GSK3\u03b2.	SIGNOR-279053
P78314	P29350	0	dephosphorylation	down-regulates	0.57	Shp-1 dephosphorylates 3bp2 and potentially downregulates 3bp2-mediated t cell antigen receptor signaling	SIGNOR-146508
P23769	P04839	1	transcriptional regulation	down-regulates quantity	0.25	These results suggest that GATA-1 is an activator and that GATA-2 is a relative competitive inhibitor of GATA-1 in the expression of the gp91(phox) gene in human eosinophils.	SIGNOR-259948
Q9UQM7	Q04760	1	phosphorylation	up-regulates activity	0.2	This study is able to show that a phosphorylation of threonine-107 (T107) in the (rate-limiting) Glyoxalase 1 (Glo1) protein, mediated by Ca2+/calmodulin-dependent kinase II delta (CamKIIδ), is associated with elevated catalytic efficiency of Glo1 (lower KM; higher Vmax).	SIGNOR-273553
Q16635	P06493	0	phosphorylation	down-regulates quantity by destabilization	0.266	Our studies suggest that phosphorylation and degradation of TAZ by Cdk1 may play important roles in apoptosis induced by antitubulin drugs.	SIGNOR-278240
Q2NKX8	P06493	0	phosphorylation	up-regulates	0.579	Following phosphorylation of pich on the cdk1 site t1063, plk1 is recruited to pich and controls its localization. Starting in prometaphase, pich accumulates at kinetochores and inner centromeres.	SIGNOR-152133
Q9BWT7	Q04759	1	relocalization	up-regulates activity	0.435	TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation	SIGNOR-272471
P21802	Q8WU20	1	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
P04198	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.33	Because GSK3\u03b2 phosphorylates Nmyc at T58, we assessed GSK3\u03b2 activation in Dex-treated MB cells.	SIGNOR-279722
P19447	P50613	0	phosphorylation	down-regulates quantity by destabilization	0.895	These results led us to propose a model that spironolactone may trigger the phosphorylation of XPB at Ser90 by CDK7, which promotes the recognition and polyubiquitination of XPB by SCFFBXL18 for proteasomal degradation.	SIGNOR-277433
P06493	P17661	1	phosphorylation	down-regulates quantity by destabilization	0.2	In line with this, we found that in Drp/MC mice desmin was hyperphosphorylated in Ser-31 by a hyperactivated Cdk-1.	SIGNOR-278331
P35222	P49841	0	phosphorylation	down-regulates activity	0.86	Wnt regulation of beta-catenin degradation is essential for development and carcinogenesis. beta-catenin degradation is initiated upon amino-terminal serine/threonine phosphorylation, which is believed to be performed by glycogen synthase kinase-3 (GSK-3) in complex with tumor suppressor proteins Axin and adnomatous polyposis coli (APC).	SIGNOR-116528
Q14814	Q16539	0	phosphorylation	up-regulates activity	0.612	Targeting of ash2l to specific genes is mediated by the transcriptional regulator mef2d. Furthermore, this interaction is modulated during differentiation through activation of the p38 mapk signaling pathway via phosphorylation of mef2d.	SIGNOR-159331
P01024	P05156	0	cleavage	down-regulates activity	0.878	FH also serves as cofactor for the serine protease factor I (FI) that cleaves C3b into iC3b, unable to form C3 convertase (Fig 1B).	SIGNOR-263489
Q9Y448	O14965	0	phosphorylation	down-regulates activity	0.261	The protein astrin has been shown to remove Kif2b from kinetochores in metaphase through competitive binding of CLASP1 (Manning et al., 2010 blue right-pointing triangle). During prometaphase, Aurora B kinase activity prevents astrin from localizing to kinetochores (Manning et al., 2010 blue right-pointing triangle; Schmidt et al., 2010 blue right-pointing triangle). This permits Kif2b to localize to kinetochores to destabilize k-MT attachments to execute error correction through Plk1-dependent recruitment and activation.	SIGNOR-252052
P07949	O15530	1	phosphorylation	up-regulates activity	0.2	Ret/ptc (rearranged in transformation/papillary thyroid carcinomas) tyrosine kinase phosphorylates and activates phosphoinositide-dependent kinase 1 (pdk1) ret/ptc phosphorylates a specific tyrosine (y9) residue located in the n-terminal region of pdk1.	SIGNOR-235863
Q15797	Q9UKE5	0	phosphorylation	down-regulates activity	0.2	Msn kinases directly phosphorylate α-helix 1 of Smad. we have identified Misshapen (Msn) and the mammalian orthologs TNIK, MINK1, and MAP4K4 as the kinases responsible for α-helix 1 phosphorylation.	SIGNOR-276334
P48730	P51532	1	phosphorylation	down-regulates quantity by destabilization	0.2	We reveal that CK1δ phosphorylates Brg1 at Ser31/Ser35 residues to facilitate the binding of Brg1 to FBW7, leading to ubiquitination-mediated degradation.	SIGNOR-277407
Q13976	Q9HCX4	1	phosphorylation	up-regulates activity	0.2	In vitro and in vivo kinase assays have revealed that cGK-Iα phosphorylates mouse TRPC7 but not mouse TRPC3. Site-directed mutagenesis analysis revealed that TRPC7 was phosphorylated by cGK-Iα at threonine 15. Phosphorylation of TRPC7 significantly suppressed carbachol-induced calcium influx and CREB phosphorylation. These data indicate that cGK-Iα interacts with and phosphorylates TRPC7, contributing to the quick and accurate regulation of calcium influx and CREB phosphorylation.	SIGNOR-263184
P26927	Q13043	1	phosphorylation	up-regulates	0.524	We directly show that okadaic acid induces phosphorylation in the activation loop of mst, and, once phosphorylated, mst is rapidly translocated to the nucleus. when thr183 in mst1 was mutated to ala, no band could be detected by oa treatment,2 indicating that thr183 was the site of phosphorylation.	SIGNOR-114289
P23560	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-266732
P16234	P12931	1	phosphorylation	up-regulates activity	0.49	The increased Src activity is mainly due to the phosphorylation of Tyr-419, rather than the dephosphorylation of Tyr-530 of Src protein. PDGFR, not FAK or EGFR, appears to be the upstream protein tyrosine kinase responsible for the detachment-induced Src activation in the lung tumor cells.	SIGNOR-247984
P04049	P62136	0	dephosphorylation	up-regulates activity	0.271	We have identified a complex comprised of Shoc2/Sur-8 and the catalytic subunit of protein phosphatase 1 (PP1c) as a highly specific M-Ras effector. M-Ras targets Shoc2-PP1c to stimulate Raf activity by dephosphorylating the S259 inhibitory site of Raf proteins	SIGNOR-251649
P55072	O00124	0	relocalization	down-regulates quantity	0.521	The human protein named Rep8 or Ubxd6 as a new cofactor of p97. Rep8 tethers p97 to the ER membrane for efficient ER-associated degradation.	SIGNOR-261002
P05771	P48067-2	1	phosphorylation	down-regulates activity	0.2	We demonstrated that the isoforms GlyT1a, GlyT1b, and GlyT1c were constitutively phosphorylated, and that phosphorylation was dramatically enhanced, in a time dependent fashion, after PKC activation by phorbol ester. The phosphorylation was PKC-dependent, since pre-incubation of the cells with bisindolylmaleimide I, a selective PKC inhibitor, abolished the phorbol ester-induced phosphorylation. Blotting with specific anti-phospho-tyrosine antibodies did not yield any signal that could correspond to GlyT1 tyrosine phosphorylation, suggesting that the phosphorylation occurs at serine and/or threonine residues. These results together suggest that conventional PKCα and/or β are responsible for the downregulation of glycine transport. We further analyzed the effect of more specific inhibitors to PKCα and PKCβ on the GlyT1 activity. As shown in Fig. 4, panels C-F, incubation of the cells with varying concentrations of the PKCβ inhibitors (referred as PKCβ inhibitor and LY333531) or the PKCα/γ (HDBBE) inhibitors did not prevent the reduction of glycine uptake triggered by PMA, suggesting that PKCα and PKCβ together regulate GlyT1 activity.	SIGNOR-262922
Q96SB4	Q9Y5S9	1	phosphorylation	down-regulates	0.261	We demonstrate that y14 is phosphorylated at its repeated arginine/serine (rs) dipeptides, likely by sr protein-specific kinases. Phosphorylation of y14 abolished its interaction with ejc components as well as factors that function downstream of the ejc.	SIGNOR-139555
Q9UHD2	Q92985	1	phosphorylation	up-regulates activity	0.768	In most cell types, IRF7 is phosphorylated and activated by IKK\u03b5 and TBK1 after viral infection.\|We found that phosphorylation of IRF7 on Ser477 and Ser479 by IKK\u03b5 or TBK1 is inhibited by ORF45.	SIGNOR-278216
P61964	Q96RG2	0	phosphorylation	up-regulates activity	0.307	Pask directly interacts with and phosphorylates Wdr5 at Ser49.\|We therefore believe that differentiation cues act, at least in part, to drive the myogenic transcriptional program via Pask activation and phosphorylation of Wdr5.	SIGNOR-278266
O00429	Q9NX47	0	polyubiquitination	down-regulates quantity by destabilization	0.2	We found that MITOL associated with and ubiquitinated mitochondrial fission protein hFis1 and Drp1.Pulse–chase experiment also indicated that MITOL overexpression promoted Drp1 turnover.	SIGNOR-271894
P49841	Q13469	1	phosphorylation	down-regulates	0.561	Gsk3 was previously shown to directly phosphorylate the n-terminal regulatory domain of nfatc1, thus antagonizing the action of calcineurin and inhibiting nuclear shuttling of nfat.	SIGNOR-179784
Q05655	Q99986	1	phosphorylation	down-regulates activity	0.285	PKC\u03b4 phosphorylates VRK1 on Ser-355 in vitro.\|PKCdelta negatively regulates VRK1 kinase activity in vitro.	SIGNOR-278219
Q9HCK8	P35716	1	transcriptional regulation	down-regulates quantity	0.2	Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells	SIGNOR-268923
O95863	Q9UEW8	0	phosphorylation	up-regulates activity	0.2	In this study, we found that STK39 also enhances SNAI1 stability by its phosphorylation at T203.\|STK39 interacts with SNAI1 and phosphorylates SNAI1 on T203.	SIGNOR-279128
P02545	P12931	0	phosphorylation	up-regulates activity	0.51	In this study, we found that the constitutively active Src Y527F mutant caused the disassembly of lamin A/C. We demonstrate that Src directly phosphorylates lamin A mainly at Tyr45 both in vitro and in intact cells.	SIGNOR-279288
P17861-2	O75460	0	post transcriptional regulation	up-regulates quantity by expression	0.647	Upon activation by oligomerization and autophosphorylation, the cytosolic RNase domain of IRE1 mediates an unconventional splicing of the mRNA of X-box-binding protein 1 (XBP1). The spliced and frameshifted transcript encodes XBP1S, a bZIP transcription factor inducing the expression of numerous UPR effector genes that enhance ER folding capacity.	SIGNOR-260183
Q06830	P24941	0	phosphorylation	down-regulates	0.254	Peroxiredoxin (prx) i is a member of the peroxiredoxin family of peroxidases and contains a consensus site (thr(90)-pro-lys-lys) for phosphorylation by cyclin-dependent kinases (cdks). This protein has now been shown to be phosphorylated specifically on thr(90) by several cdks, including cdc2, in vitro. Phosphorylation of prx i on thr(90) reduced the peroxidase activity of this protein by 80%.Prx i was also phosphorylated, with an efficiency similar to that observed with cdc2, when incubated in vitro with cdk2, cdk4, or cdk6 that had been immunoprecipitated from hela cell lysates with specific antibodies (data not shown).	SIGNOR-87101
O94921	P37802	1	phosphorylation	down-regulates activity	0.315	This newly identified oncogene–tumor suppressor cascade, where oncogenic PFTK1 inactivates a tumor suppressor gene TAGLN2 via phosphorylation\|. Our data therefore underline much importance for S83 and S163 residues on TAGLN2 in its actin-binding capacity.	SIGNOR-265103
P67870	Q13698	1	phosphorylation	up-regulates activity	0.2	To identify the regulatory sites of phosphorylation under physiologically relevant conditions, Ca(V)1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac Ca(V)1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that Ca(V)1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas Ca(V)1.1-T1579 is a substrate for casein kinase 2.	SIGNOR-263115
P55212	P49810	1	cleavage	up-regulates activity	0.363	In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329.	SIGNOR-261750
Q7LBC6	P68431	1	demethylation	down-regulates activity	0.2	We have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. JHDM2A exhibits hormone-dependent recruitment to androgen-receptor target genes, resulting in H3K9 demethylation and transcriptional activation. Thus, our work identifies a histone demethylase and links its function to hormone-dependent transcriptional activation.	SIGNOR-266634
P15976	Q9NQU5	0	phosphorylation	up-regulates activity	0.2	In addition, PAK5 knockdown also markedly reduced the association of GATA1 with HDAC3/4.\|PAK5 phosphorylates the transcription factor GATA1 mainly at Ser161 and Ser 187, phosphorylated GATA1 recruits more HDAC3/4 to the promoter of E-cadherin and consequently suppresses the transcription of E-cadherin gene and promotes the EMT of breast cancer cells.	SIGNOR-278415
Q9H3R0	P42574	0	cleavage	down-regulates activity	0.2	JMJD2C as a novel substrate for caspase-3 (cysteine-aspartic acid protease-3), and cleavage of JMJD2C by caspase-3 led to inactivation of JMJD2C demethylase activity and elevation of H3K9 methylation levels.	SIGNOR-263870
P98177	Q99576	0	relocalization	down-regulates activity	0.253	GILZ inhibits FOXO1, FOXO3, and FOXO4 transcriptional activities measured with natural or synthetic FOXO-responsive promoters in HL-60 cells.	SIGNOR-256148
P17612	P07196	1	phosphorylation	down-regulates activity	0.2	Phosphorylation of neurofilament-L protein (NF-L) by the catalytic subunit of cAMP-dependent protein kinase (A-kinase) inhibits the reassembly of NF-L and disassembles filamentous NF-L.	SIGNOR-252401
P06493	P31350	1	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
P23443	Q6R327	1	phosphorylation	down-regulates	0.715	Phosphorylation of rictor on thr1135 did not affect mtorc2 assembly, kinase activity, or cellular localization. However, cells expressing a rictor t1135a mutant were found to have increased mtorc2-dependent phosphorylation of akt	SIGNOR-161995
P62330	P48426	1	null	up-regulates activity	0.338	Effects of ARF6 upon Axonogenesis Are Mediated by Phosphatidyl-inositol-4-phosphate 5-Kinase α. activated ARF6 stimulates the lipid-modifying enzyme PI(4)P 5-Kinase, leading to local increases in plasma membrane PIP2 and changes in actin dynamics. Alternatively, activation of Rac1 by upstream Rac1 activators or indirectly by ARF6-GTP results in stimulation of actin polymerization.	SIGNOR-264911
P31749	P12268	1	phosphorylation	up-regulates activity	0.386	Further, we have demonstrated an in vivo association of IMPDH and PKB/Akt by co‐immunoprecipitation from COS cells expressing a constitutively active form of PKB/Akt. Finally, we were able to show that this constitutively active PKB/Akt could phosphorylate IMPDH in vitro. Thus, the interplay between PKB/Akt and IMPDH reported here could suggest that PKB/Akt activation leads to IMPDH type II activation which in turn prepares the cell for entry into S phase.	SIGNOR-261262
Q86Y13	Q16777	1	monoubiquitination	up-regulates activity	0.2	2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.	SIGNOR-271754
P55017	Q9UEW8	0	phosphorylation	down-regulates activity	0.484	SPAK directly phosphorylates NCC and its effects on NCC are universally associated with phosphorylation\|This adds to the evidence that SPAK-mediated phosphorylation acts primarily to increase activity of individual cotransporters without affecting the amount of NCC on the surface\| the kinase (SPAK) that phosphorylates NCC at T53	SIGNOR-264623
P15941	P43403	0	phosphorylation	up-regulates activity	0.448	Indeed, the present results demonstrate that ZAP-70 phosphorylates MUC1-CD and that the MUC1-CD Y-20 site functions, at least in part, as a ZAP-70 substrate (Fig. 4C). In this regard, the in vivo phosphorylation data indicate that ZAP-70 may also contribute to phosphorylation of MUC1-CD Y-46.The results further show that ZAP-70 phosphorylation of MUC1-CD stimulates the interaction of MUC1 andBeta-catenin.	SIGNOR-247039
Q13131	P36956	1	phosphorylation	down-regulates activity	0.36	Ampk was recently found to phosphorylate a conserved serine near the cleavage site within srebp1, suppressing its activation	SIGNOR-176497
Q01581	P13674	0	transcriptional regulation	up-regulates quantity by expression	0.2	In this study, we found that the prolyl 4-hydroxylase (P4H) subunit P4HA1 protects NPC cells from erastin-induced ferroptosis by activating HMGCS1, a key enzyme in the mevalonate pathway. Our results show that HMGCS1 and HMGCR are regulated by P4HA subunits at the transcriptional level (Fig. S4).	SIGNOR-279853
P07949	Q9ULV8	0	ubiquitination	down-regulates quantity by destabilization	0.368	Here we show that Cbl-c binds wild-type and MEN2A isoforms of the receptor tyrosine kinase, RET, and that Cbl-c enhances ubiquitination and degradation of activated RET.\|We show that Cbl-c negatively regulates RET by ubiquitinating and downregulating the activated RTK while Enigma positively regulates activated RET by preventing Cbl-c binding to RET and thus preventing RET ubiquitination and degradation while promoting RET mitogenic signaling.	SIGNOR-278674
Q9HAU4	Q15797	1	polyubiquitination	down-regulates quantity by destabilization	0.725	Here, we report the identification of Smurf2, a new member of the Hect family of E3 ubiquitin ligases. Smurf2 selectively interacts with receptor-regulated Smads and preferentially targets Smad1 for ubiquitination and proteasome-mediated degradation. At higher expression levels, Smurf2 also decreases the protein levels of Smad2, but not Smad3.	SIGNOR-272936
Q9NRM7	Q14872	1	phosphorylation	down-regulates activity	0.2	The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1\|the Hippo pathway kinase LATS phosphorylates and inhibits MTF1\|LATS phosphorylates MTF1 at S152 and disrupts its association with the promoters of heavy metal response genes, resulting in the loss of heavy metal response gene expression	SIGNOR-275475
Q9ULV8	P00533	1	polyubiquitination	down-regulates quantity by destabilization	0.761	In summary, we have shown that CBLC and AIP4 can interact and that these two E3 ligases could contribute to down-regulate EGFR signaling by ubiquitination.	SIGNOR-272605
P20749	P31749	0	phosphorylation	up-regulates quantity by stabilization	0.494	Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA.	SIGNOR-277358
Q13137	Q9UHD2	0	phosphorylation	up-regulates activity	0.795	Furthermore, we found that TBC1D9-regulated TBK1 activation and recruitment of NDP52 and ULK1 complex to damaged mitochondria (Fig.\u00a0 xref ).\|TBK1 can phosphorylate p62, OPTN, and NDP52 to promote selective autophagy by facilitating their interaction with LC3, ubiquitin, and RAB35, respectively xref , xref , xref .	SIGNOR-280151
O75385	P09467	1	phosphorylation	down-regulates activity	0.2	Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).	SIGNOR-274031
Q7KZI7	Q8TEW0	1	phosphorylation	up-regulates	0.493	Gab1 brings par1 and par3 into a transient complex, stimulating par3 phosphorylation by par1	SIGNOR-198742
P53350	Q9NWD9	1	phosphorylation	up-regulates activity	0.2	In addition, the inhibition of PLK1 activity by BI2536 treatment sharply reduced BEX4 protein, which was localized at the centrosomes in the HeLa cells or the GFP-BEX4 stable cell lines.\|PLK1 directly phosphorylates BEX4 at T107 and contributes to BEX4-induced aneuploidy.	SIGNOR-279550
P25874	Q7LBC6	0	transcriptional regulation	up-regulates quantity by expression	0.2	We show that Jhdm2a expression is induced by beta-adrenergic stimulation, and that Jhdm2a directly regulates peroxisome proliferator-activated receptor alpha (Ppara) and Ucp1 expression.	SIGNOR-266638
Q13158	O14733	0	phosphorylation	down-regulates activity	0.497	The results clearly show that fadd phosphorylation at ser194 affects functions both upstream and downstream of the mekk1/mkk7/jnk1 pathway and is closely associated with chemosensitivity in prostate cancer cells	SIGNOR-123164
Q9Y2U5	Q15208	1	phosphorylation	up-regulates quantity by stabilization	0.402	Our data suggest that Ser91 phosphorylation of STK38 by MEKK2 possibly blocks the interaction of calpain with STK38 or disrupts proper conformation for cleaving, thereby protecting STK38 from calpain-dependent degradation.	SIGNOR-279066
Q9H2X6	Q9NY61	1	phosphorylation	down-regulates quantity	0.346	HIPK2 phosphorylates Che-1.\|Here we demonstrate that HIPK2, a proapoptotic kinase, is involved in Che-1 degradation.	SIGNOR-278942
Q9BSQ5	O00506	0	phosphorylation	up-regulates	0.5	CCM2 can be phosphorylated by STK25, and the kinase activity of STK25 is required for death signaling.	SIGNOR-263144
O14986	P43405	0	phosphorylation	down-regulates activity	0.2	We identified spleen tyrosine kinase (Syk), which is activated by oxidants, as a candidate PIP5Kbeta kinase in this pathway, and mapped the oxidant-sensitive tyrosine phosphorylation site to residue 105. The PIP5KbetaY105E phosphomimetic is catalytically inactive and cytosolic, whereas the Y105F non-phosphorylatable mutant has higher intrinsic lipid kinase activity and is much more membrane associated than wild type PIP5Kbeta.	SIGNOR-276227
Q15154	Q8N4C6	1	relocalization	up-regulates	0.406	Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome	SIGNOR-95077
P36888	P24752	1	phosphorylation	up-regulates activity	0.2	We previously reported that the mitochondrial fraction of FLT3 activates acetyl-CoA acetyltransferase ACAT1 in mitochondria via Y407 phosphorylation to acetylate and inhibit mitochondrial pyruvate dehydrogenase A (PDHA) and PDH phosphatase 1 (PDP1)	SIGNOR-267628
O95786	P55072	0	ubiquitination	down-regulates quantity by destabilization	0.2	Here, we report a new role for p97 with Npl4-Ufd1 as its cofactor in reducing antiviral innate immune responses by facilitating proteasomal degradation of RIG-I. The p97 complex is able to directly bind both non-ubiquitinated RIG-I and the E3 ligase RNF125, promoting K48-linked ubiquitination of RIG-I at residue K181.	SIGNOR-261000
P05546	P08311	0	cleavage	down-regulates activity	0.444	Amino acid sequence analysis led to the conclusion that both neutrophil elastase and cathepsin G cleave HC at Ile66, which does not affect HC activity, and at Val439, near the reactive site Leu444, which inactivates HC.	SIGNOR-256509
Q9UPZ9	Q8IZL9	0	phosphorylation	up-regulates	0.2	Recombinant cak1p phosphorylates thr-157 in the tdy motif of recombinant ick and activates its activity in vitro.	SIGNOR-138420
O15198	O00238	0	phosphorylation	up-regulates activity	0.708	Two types of bmp-induced signaling pathways are known, the smad and p38 mapk pathways. In the former case, bmpr1 phosphorylates smad-1,-5,-8, which forms a complex with smad4 that translocates into the nucleus and regulates gene expression.	SIGNOR-255264
O43462	P36956	1	cleavage	up-regulates activity	0.651	In order to activate transcription, the NH2-terminal domain of the SREBP must be released from the membrane so that it can enter the nucleus. This release has been studied most extensively for one of the SREBPs, namely, SREBP-2. However, the mechanism appears to be similar for the other SREBPs (SREBP-1a and -1c) (1). Release of the NH2-terminal domain is accomplished by a two-step proteolytic event that is regulated by sterols (3). In sterol-depleted mammalian cells, this proteolysis is initiated by the Site-1 protease (S1P), which cleaves human SREBP-2 between the Leu522-Ser523 bond in the sequence RSVL S (4). This cleavage requires formation of a complex between SREBP and SCAP, a polytopic membrane protein of the ER, and it is prevented when this complex is disrupted	SIGNOR-267499
P54646	Q9H2X6	1	phosphorylation	down-regulates activity	0.2	AMPKalpha2-mediated inhibition of WIP1 phosphorylation by HIPK2\|Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKalpha2 in vitro	SIGNOR-275485
P29350	Q13114	1	dephosphorylation	down-regulates activity	0.2	We identified a direct interaction between SHP‐1 and TRAF3; the association between these two proteins resulted in diminished recruitment of CK1ε to TRAF3 and inhibited its K63‐linked ubiquitination; SHP‐1 inhibited K63‐linked ubiquitination of TRAF3 by promoting dephosphorylation at Tyr116 and Tyr446.	SIGNOR-277527
P06493	O00418	1	phosphorylation	down-regulates	0.368	Phosphorylation at ser359 inhibits eef2k activity even at high calcium concentrations. we demonstrate that cdc2 contributes to controlling eef2 phosphorylation in cells. inactivation of eef2k by cdc2 may serve to keep eef2 active during mitosis	SIGNOR-177982

Q13224

P68400

0

phosphorylation

down-regulates

0.324

Here we show that casein kinase ii (ck2) phosphorylates the serine residue (ser1480) within the c-terminal pdz ligand (iesdv) of the nr2b subunit of nmdar in vitro and in vivo. Phosphorylation of ser1480 disrupts the interaction of nr2b with the pdz domains of psd-95 and sap102 and decreases surface nr2b expression in neurons.

SIGNOR-130336

Q00535

Q96SB3

1

phosphorylation

down-regulates quantity

0.396

CDK5 decreased the expression of both spinophilin (30%) and neurabin (64%).|This suggests that CDK5 phosphorylation of spinophilin at Ser17 is not responsible for the CDK5 dependent increase in the spinophilin and PP1 association.

SIGNOR-279453

Q02078

P23409

1

transcriptional regulation

up-regulates quantity by expression

0.589

Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis.

SIGNOR-238709

P50539

P14635

1

transcriptional regulation

down-regulates quantity by repression

0.266

Mxi1 inhibits the proliferation of U87 glioma cells through down-regulation of cyclin B1 gene expression | Mxi1 inhibits the promoter activity of the cyclin B1 gene.

SIGNOR-266064

P06400

Q00535

0

phosphorylation

down-regulates

0.336

Phosphorylation was observed 6 hours after p25 induction and was abolished in the presence of a cdk5 inhibitor, roscovitine, which does not inhibit the usual rb cyclin-d kinases cdk4 and cdk6. Furthermore, analyses of levels and subcellular localization of cdk-related cyclins did not reveal any change following cdk5 activation, arguing for a direct effect of cdk5 activity on rb protein. Rb phosphorylation was visualized using phosphorylation-dependent antibodies (p-rbser795 and p-rbser807/811).

SIGNOR-134468

P25098

Q99835

1

phosphorylation

up-regulates

0.2

We find that two molecules interact with mammalian smo in an activation-dependent manner: g protein-coupled receptor kinase 2 (grk2) leads to phosphorylation of smo, and beta-arrestin 2 fused to green fluorescent protein interacts with smo. Ck1a, grk2, and another still-unidentified protein kinase phosphorylate the c-tail of mammalian smo in the presence of hh proteins

SIGNOR-174539

P43405

Q8N6F7

1

phosphorylation

up-regulates activity

0.356

Herein, we demonstrate phosphorylation of HGAL by Syk and Lyn kinases at tyrosines Y80, Y86, Y106Y107, Y128, and Y148. Y148 (in black) was already phosphorylated before the addition of kinases. We demonstrate that Grb2 facilitates HGAL and Syk binding following BCR stimulation but does not affect the HGAL-mediated increase in Syk kinase activity. Previous studies showed that Grb2 inhibits BCR signaling by decreasing the activation of Syk by Lyn.11 Thus, while HGAL and Grb2 oppositely affect Syk kinase activity, this is not due to direct Grb2 effects on HGAL-mediated Syk kinase activation.

SIGNOR-273570

P04637

O95831

1

transcriptional regulation

up-regulates quantity by expression

0.351

P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway.

SIGNOR-267462

P05771

O60346

0

dephosphorylation

down-regulates quantity

0.341

Here we show that the two PHLPP isoforms, PHLPP1 and PHLPP2, also dephosphorylate the hydrophobic motif on PKC betaII, an event that shunts PKC to the detergent-insoluble fraction, effectively terminating its life cycle

SIGNOR-237047

Q00987

Q93009

0

deubiquitination

up-regulates

0.77

Subsequently, hausp was shown to deubiquitinate mdm2 and mdmx, thereby stabilizing these proteins.

SIGNOR-139450

P22694

P08138

1

phosphorylation

up-regulates

0.625

Pka phosphorylates the p75 receptor and regulates its localization to lipid rafts. activation of camp?PKA Is required for translocation of p75ntr to lipid rafts, and for biochemical and biological activities of p75ntr, such as inactivation of rho and the neurite outgrowth.

SIGNOR-99755

P25098

Q05655

0

phosphorylation

up-regulates activity

0.2

Phosphorylation of GRK2 by protein kinase C abolishes its inhibition by calmodulin. In vitro, GRK2 was preferentially phosphorylated by PKC isoforms alpha, gamma, and delta. Two-dimensional peptide mapping of PKCalpha-phosphorylated GRK2 showed a single site of phosphorylation, which was identified as serine 29 by HPLC-MS. A S29A mutant of GRK2 was not phosphorylated by PKC in vitro and showed no phorbol ester-stimulated phosphorylation when transfected into human embryonic kidney (HEK)293 cells.

SIGNOR-249059

O94788

Q05086

0

ubiquitination

down-regulates quantity by destabilization

0.2

Hyperactivity of E3 ubiquitin (Ub) ligase UBE3A, stemming from 15q11-q13 copy number variations, accounts for 1%-3% of ASD cases worldwide, but the underlying mechanisms remain incompletely characterized. Here we report that the functionality of ALDH1A2, the rate-limiting enzyme of retinoic acid (RA) synthesis, is negatively regulated by UBE3A in a ubiquitylation-dependent manner.

SIGNOR-265135

P24941

P49459

1

phosphorylation

up-regulates

0.374

Hhr6a is phosphorylated in vitro by cdk-1 and -2 on ser120, a residue conserved in all hhr6a homologues, resulting in a 4-fold increase in its ubiquitin-conjugating activity.

SIGNOR-116508

Q9Y6H5

O60260

0

ubiquitination

down-regulates quantity by destabilization

0.2

Here we show that parkin interacts with and ubiquitinates the alpha-synuclein-interacting protein, synphilin-1.

SIGNOR-278550

Q38SD2

P30622

1

phosphorylation

up-regulates activity

0.398

LRRK1 phosphorylates CLIP-170 at Thr1384, located in its C-terminal zinc knuckle motif, and this promotes the association of CLIP-170 with dynein-dynactin complexes.

SIGNOR-275469

P18848

P05198

0

transcriptional regulation

down-regulates quantity

0.64

ER stress, viral infection, and other cellular stress signals activate PERK, PKR, HRI, and GCN2 kinases that converge on phosphorylation of eIF2alpha, the core of ISR. This leads to global attenuation of Cap Âdependent translation while concomitantly initiates the preferential translation of ISR Âspecific mRNAs, such as ATF4. ATF4 is the main effector of the ISR. eIF2alpha phosphorylation causes a reduction in global protein synthesis while allowing the translation of selected genes including activating transcription factor 4 (ATF4), aiding cell survival and recovery

SIGNOR-260169

Q92949

O75602

1

transcriptional regulation

up-regulates quantity by expression

0.447

FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).

SIGNOR-266935

P78527

P52945

1

phosphorylation

down-regulates quantity by destabilization

0.307

The interaction of PDX-1 with Ku subunits and its phosphorylation on threonine 11 by the DNA-PK appear to be implicated in its degradation by the proteosome.

SIGNOR-225542

O14965

Q8NHV4

1

phosphorylation

up-regulates activity

0.557

Microtubule nucleation during central spindle assembly requires NEDD1 phosphorylation on serine 405 by Aurora A| In the absence of Aurora A, the HURP (also known as DLGAP5) and NEDD1 proteins that are involved in nucleation of microtubules fail to concentrate in the midzone.

SIGNOR-272965

P00519

O00401

1

phosphorylation

up-regulates activity

0.55

Abl phosphorylates N-WASP on tyrosines 175 and 256. Phosphorylation at this site stabilizes the active conformation of N-WASP, resulting in comet tail elongation.

SIGNOR-251437

P60852

Q5JUK2

0

transcriptional regulation

up-regulates quantity by expression

0.2

Cotransfection of a mouse Sohlh1 expression vector with E box-containing promoter regions of mouse Lhx8, Zp1, and Zp3 fused to luciferase resulted in significant transactivation . Mutation of the E box sequences abolished SOHLH1-dependent stimulation. Thus, Lhx8, Zp1, and Zp3 are likely direct downstream target genes of SOHLH1 through the E box elements in their promoters.

SIGNOR-266077

P49841

Q6IA17

1

phosphorylation

down-regulates quantity by destabilization

0.2

Activation of GSK3beta promotes Sigirr degradation in the proteasome .|Taken together, IL-37-induced Sigirr internalization is dependent on phosphorylation of Sigirr in T372 residue by GSK3\u03b2.

SIGNOR-279053

P78314

P29350

0

dephosphorylation

down-regulates

0.57

Shp-1 dephosphorylates 3bp2 and potentially downregulates 3bp2-mediated t cell antigen receptor signaling

SIGNOR-146508

P23769

P04839

1

transcriptional regulation

down-regulates quantity

0.25

These results suggest that GATA-1 is an activator and that GATA-2 is a relative competitive inhibitor of GATA-1 in the expression of the gp91(phox) gene in human eosinophils.

SIGNOR-259948

Q9UQM7

Q04760

1

phosphorylation

up-regulates activity

0.2

This study is able to show that a phosphorylation of threonine-107 (T107) in the (rate-limiting) Glyoxalase 1 (Glo1) protein, mediated by Ca2+/calmodulin-dependent kinase II delta (CamKIIδ), is associated with elevated catalytic efficiency of Glo1 (lower KM; higher Vmax).

SIGNOR-273553

Q16635

P06493

0

phosphorylation

down-regulates quantity by destabilization

0.266

Our studies suggest that phosphorylation and degradation of TAZ by Cdk1 may play important roles in apoptosis induced by antitubulin drugs.

SIGNOR-278240

Q2NKX8

P06493

0

phosphorylation

up-regulates

0.579

Following phosphorylation of pich on the cdk1 site t1063, plk1 is recruited to pich and controls its localization. Starting in prometaphase, pich accumulates at kinetochores and inner centromeres.

SIGNOR-152133

Q9BWT7

Q04759

1

relocalization

up-regulates activity

0.435

TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation

SIGNOR-272471

P21802

Q8WU20

1

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

P04198

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.33

Because GSK3\u03b2 phosphorylates Nmyc at T58, we assessed GSK3\u03b2 activation in Dex-treated MB cells.

SIGNOR-279722

P19447

P50613

0

phosphorylation

down-regulates quantity by destabilization

0.895

These results led us to propose a model that spironolactone may trigger the phosphorylation of XPB at Ser90 by CDK7, which promotes the recognition and polyubiquitination of XPB by SCFFBXL18 for proteasomal degradation.

SIGNOR-277433

P06493

P17661

1

phosphorylation

down-regulates quantity by destabilization

0.2

In line with this, we found that in Drp/MC mice desmin was hyperphosphorylated in Ser-31 by a hyperactivated Cdk-1.

SIGNOR-278331

P35222

P49841

0

phosphorylation

down-regulates activity

0.86

Wnt regulation of beta-catenin degradation is essential for development and carcinogenesis. beta-catenin degradation is initiated upon amino-terminal serine/threonine phosphorylation, which is believed to be performed by glycogen synthase kinase-3 (GSK-3) in complex with tumor suppressor proteins Axin and adnomatous polyposis coli (APC).

SIGNOR-116528

Q14814

Q16539

0

phosphorylation

up-regulates activity

0.612

Targeting of ash2l to specific genes is mediated by the transcriptional regulator mef2d. Furthermore, this interaction is modulated during differentiation through activation of the p38 mapk signaling pathway via phosphorylation of mef2d.

SIGNOR-159331

P01024

P05156

0

cleavage

down-regulates activity

0.878

FH also serves as cofactor for the serine protease factor I (FI) that cleaves C3b into iC3b, unable to form C3 convertase (Fig 1B).

SIGNOR-263489

Q9Y448

O14965

0

phosphorylation

down-regulates activity

0.261

The protein astrin has been shown to remove Kif2b from kinetochores in metaphase through competitive binding of CLASP1 (Manning et al., 2010 blue right-pointing triangle). During prometaphase, Aurora B kinase activity prevents astrin from localizing to kinetochores (Manning et al., 2010 blue right-pointing triangle; Schmidt et al., 2010 blue right-pointing triangle). This permits Kif2b to localize to kinetochores to destabilize k-MT attachments to execute error correction through Plk1-dependent recruitment and activation.

SIGNOR-252052

P07949

O15530

1

phosphorylation

up-regulates activity

0.2

Ret/ptc (rearranged in transformation/papillary thyroid carcinomas) tyrosine kinase phosphorylates and activates phosphoinositide-dependent kinase 1 (pdk1) ret/ptc phosphorylates a specific tyrosine (y9) residue located in the n-terminal region of pdk1.

SIGNOR-235863

Q15797

Q9UKE5

0

phosphorylation

down-regulates activity

0.2

Msn kinases directly phosphorylate α-helix 1 of Smad. we have identified Misshapen (Msn) and the mammalian orthologs TNIK, MINK1, and MAP4K4 as the kinases responsible for α-helix 1 phosphorylation.

SIGNOR-276334

P48730

P51532

1

phosphorylation

down-regulates quantity by destabilization

0.2

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

SIGNOR-277407

Q13976

Q9HCX4

1

phosphorylation

up-regulates activity

0.2

In vitro and in vivo kinase assays have revealed that cGK-Iα phosphorylates mouse TRPC7 but not mouse TRPC3. Site-directed mutagenesis analysis revealed that TRPC7 was phosphorylated by cGK-Iα at threonine 15. Phosphorylation of TRPC7 significantly suppressed carbachol-induced calcium influx and CREB phosphorylation. These data indicate that cGK-Iα interacts with and phosphorylates TRPC7, contributing to the quick and accurate regulation of calcium influx and CREB phosphorylation.

SIGNOR-263184

P26927

Q13043

1

phosphorylation

up-regulates

0.524

We directly show that okadaic acid induces phosphorylation in the activation loop of mst, and, once phosphorylated, mst is rapidly translocated to the nucleus. when thr183 in mst1 was mutated to ala, no band could be detected by oa treatment,2 indicating that thr183 was the site of phosphorylation.

SIGNOR-114289

P23560

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-266732

P16234

P12931

1

phosphorylation

up-regulates activity

0.49

The increased Src activity is mainly due to the phosphorylation of Tyr-419, rather than the dephosphorylation of Tyr-530 of Src protein. PDGFR, not FAK or EGFR, appears to be the upstream protein tyrosine kinase responsible for the detachment-induced Src activation in the lung tumor cells.

SIGNOR-247984

P04049

P62136

0

dephosphorylation

up-regulates activity

0.271

We have identified a complex comprised of Shoc2/Sur-8 and the catalytic subunit of protein phosphatase 1 (PP1c) as a highly specific M-Ras effector. M-Ras targets Shoc2-PP1c to stimulate Raf activity by dephosphorylating the S259 inhibitory site of Raf proteins

SIGNOR-251649

P55072

O00124

0

relocalization

down-regulates quantity

0.521

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

SIGNOR-261002

P05771

P48067-2

1

phosphorylation

down-regulates activity

0.2

We demonstrated that the isoforms GlyT1a, GlyT1b, and GlyT1c were constitutively phosphorylated, and that phosphorylation was dramatically enhanced, in a time dependent fashion, after PKC activation by phorbol ester. The phosphorylation was PKC-dependent, since pre-incubation of the cells with bisindolylmaleimide I, a selective PKC inhibitor, abolished the phorbol ester-induced phosphorylation. Blotting with specific anti-phospho-tyrosine antibodies did not yield any signal that could correspond to GlyT1 tyrosine phosphorylation, suggesting that the phosphorylation occurs at serine and/or threonine residues. These results together suggest that conventional PKCα and/or β are responsible for the downregulation of glycine transport. We further analyzed the effect of more specific inhibitors to PKCα and PKCβ on the GlyT1 activity. As shown in Fig. 4, panels C-F, incubation of the cells with varying concentrations of the PKCβ inhibitors (referred as PKCβ inhibitor and LY333531) or the PKCα/γ (HDBBE) inhibitors did not prevent the reduction of glycine uptake triggered by PMA, suggesting that PKCα and PKCβ together regulate GlyT1 activity.

SIGNOR-262922

Q96SB4

Q9Y5S9

1

phosphorylation

down-regulates

0.261

We demonstrate that y14 is phosphorylated at its repeated arginine/serine (rs) dipeptides, likely by sr protein-specific kinases. Phosphorylation of y14 abolished its interaction with ejc components as well as factors that function downstream of the ejc.

SIGNOR-139555

Q9UHD2

Q92985

1

phosphorylation

up-regulates activity

0.768

In most cell types, IRF7 is phosphorylated and activated by IKK\u03b5 and TBK1 after viral infection.|We found that phosphorylation of IRF7 on Ser477 and Ser479 by IKK\u03b5 or TBK1 is inhibited by ORF45.

SIGNOR-278216

P61964

Q96RG2

0

phosphorylation

up-regulates activity

0.307

Pask directly interacts with and phosphorylates Wdr5 at Ser49.|We therefore believe that differentiation cues act, at least in part, to drive the myogenic transcriptional program via Pask activation and phosphorylation of Wdr5.

SIGNOR-278266

O00429

Q9NX47

0

polyubiquitination

down-regulates quantity by destabilization

0.2

We found that MITOL associated with and ubiquitinated mitochondrial fission protein hFis1 and Drp1.Pulse–chase experiment also indicated that MITOL overexpression promoted Drp1 turnover.

SIGNOR-271894

P49841

Q13469

1

phosphorylation

down-regulates

0.561

Gsk3 was previously shown to directly phosphorylate the n-terminal regulatory domain of nfatc1, thus antagonizing the action of calcineurin and inhibiting nuclear shuttling of nfat.

SIGNOR-179784

Q05655

Q99986

1

phosphorylation

down-regulates activity

0.285

PKC\u03b4 phosphorylates VRK1 on Ser-355 in vitro.|PKCdelta negatively regulates VRK1 kinase activity in vitro.

SIGNOR-278219

Q9HCK8

P35716

1

transcriptional regulation

down-regulates quantity

0.2

Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells

SIGNOR-268923

O95863

Q9UEW8

0

phosphorylation

up-regulates activity

0.2

In this study, we found that STK39 also enhances SNAI1 stability by its phosphorylation at T203.|STK39 interacts with SNAI1 and phosphorylates SNAI1 on T203.

SIGNOR-279128

P02545

P12931

0

phosphorylation

up-regulates activity

0.51

In this study, we found that the constitutively active Src Y527F mutant caused the disassembly of lamin A/C. We demonstrate that Src directly phosphorylates lamin A mainly at Tyr45 both in vitro and in intact cells.

SIGNOR-279288

P17861-2

O75460

0

post transcriptional regulation

up-regulates quantity by expression

0.647

Upon activation by oligomerization and autophosphorylation, the cytosolic RNase domain of IRE1 mediates an unconventional splicing of the mRNA of X-box-binding protein 1 (XBP1). The spliced and frameshifted transcript encodes XBP1S, a bZIP transcription factor inducing the expression of numerous UPR effector genes that enhance ER folding capacity.

SIGNOR-260183

Q06830

P24941

0

phosphorylation

down-regulates

0.254

Peroxiredoxin (prx) i is a member of the peroxiredoxin family of peroxidases and contains a consensus site (thr(90)-pro-lys-lys) for phosphorylation by cyclin-dependent kinases (cdks). This protein has now been shown to be phosphorylated specifically on thr(90) by several cdks, including cdc2, in vitro. Phosphorylation of prx i on thr(90) reduced the peroxidase activity of this protein by 80%.Prx i was also phosphorylated, with an efficiency similar to that observed with cdc2, when incubated in vitro with cdk2, cdk4, or cdk6 that had been immunoprecipitated from hela cell lysates with specific antibodies (data not shown).

SIGNOR-87101

O94921

P37802

1

phosphorylation

down-regulates activity

0.315

This newly identified oncogene–tumor suppressor cascade, where oncogenic PFTK1 inactivates a tumor suppressor gene TAGLN2 via phosphorylation|. Our data therefore underline much importance for S83 and S163 residues on TAGLN2 in its actin-binding capacity.

SIGNOR-265103

P67870

Q13698

1

phosphorylation

up-regulates activity

0.2

To identify the regulatory sites of phosphorylation under physiologically relevant conditions, Ca(V)1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac Ca(V)1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that Ca(V)1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas Ca(V)1.1-T1579 is a substrate for casein kinase 2.

SIGNOR-263115

P55212

P49810

1

cleavage

up-regulates activity

0.363

In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329.

SIGNOR-261750

Q7LBC6

P68431

1

demethylation

down-regulates activity

0.2

We have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9. JHDM2A exhibits hormone-dependent recruitment to androgen-receptor target genes, resulting in H3K9 demethylation and transcriptional activation. Thus, our work identifies a histone demethylase and links its function to hormone-dependent transcriptional activation.

SIGNOR-266634

P15976

Q9NQU5

0

phosphorylation

up-regulates activity

0.2

In addition, PAK5 knockdown also markedly reduced the association of GATA1 with HDAC3/4.|PAK5 phosphorylates the transcription factor GATA1 mainly at Ser161 and Ser 187, phosphorylated GATA1 recruits more HDAC3/4 to the promoter of E-cadherin and consequently suppresses the transcription of E-cadherin gene and promotes the EMT of breast cancer cells.

SIGNOR-278415

Q9H3R0

P42574

0

cleavage

down-regulates activity

0.2

JMJD2C as a novel substrate for caspase-3 (cysteine-aspartic acid protease-3), and cleavage of JMJD2C by caspase-3 led to inactivation of JMJD2C demethylase activity and elevation of H3K9 methylation levels.

SIGNOR-263870

P98177

Q99576

0

relocalization

down-regulates activity

0.253

GILZ inhibits FOXO1, FOXO3, and FOXO4 transcriptional activities measured with natural or synthetic FOXO-responsive promoters in HL-60 cells.

SIGNOR-256148

P17612

P07196

1

phosphorylation

down-regulates activity

0.2

Phosphorylation of neurofilament-L protein (NF-L) by the catalytic subunit of cAMP-dependent protein kinase (A-kinase) inhibits the reassembly of NF-L and disassembles filamentous NF-L.

SIGNOR-252401

P06493

P31350

1

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

P23443

Q6R327

1

phosphorylation

down-regulates

0.715

Phosphorylation of rictor on thr1135 did not affect mtorc2 assembly, kinase activity, or cellular localization. However, cells expressing a rictor t1135a mutant were found to have increased mtorc2-dependent phosphorylation of akt

SIGNOR-161995

P62330

P48426

1

null

up-regulates activity

0.338

Effects of ARF6 upon Axonogenesis Are Mediated by Phosphatidyl-inositol-4-phosphate 5-Kinase α. activated ARF6 stimulates the lipid-modifying enzyme PI(4)P 5-Kinase, leading to local increases in plasma membrane PIP2 and changes in actin dynamics. Alternatively, activation of Rac1 by upstream Rac1 activators or indirectly by ARF6-GTP results in stimulation of actin polymerization.

SIGNOR-264911

P31749

P12268

1

phosphorylation

up-regulates activity

0.386

Further, we have demonstrated an in vivo association of IMPDH and PKB/Akt by co‐immunoprecipitation from COS cells expressing a constitutively active form of PKB/Akt. Finally, we were able to show that this constitutively active PKB/Akt could phosphorylate IMPDH in vitro. Thus, the interplay between PKB/Akt and IMPDH reported here could suggest that PKB/Akt activation leads to IMPDH type II activation which in turn prepares the cell for entry into S phase.

SIGNOR-261262

Q86Y13

Q16777

1

monoubiquitination

up-regulates activity

0.2

2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.

SIGNOR-271754

P55017

Q9UEW8

0

phosphorylation

down-regulates activity

0.484

SPAK directly phosphorylates NCC and its effects on NCC are universally associated with phosphorylation|This adds to the evidence that SPAK-mediated phosphorylation acts primarily to increase activity of individual cotransporters without affecting the amount of NCC on the surface| the kinase (SPAK) that phosphorylates NCC at T53

SIGNOR-264623

P15941

P43403

0

phosphorylation

up-regulates activity

0.448

Indeed, the present results demonstrate that ZAP-70 phosphorylates MUC1-CD and that the MUC1-CD Y-20 site functions, at least in part, as a ZAP-70 substrate (Fig. 4C). In this regard, the in vivo phosphorylation data indicate that ZAP-70 may also contribute to phosphorylation of MUC1-CD Y-46.The results further show that ZAP-70 phosphorylation of MUC1-CD stimulates the interaction of MUC1 andBeta-catenin.

SIGNOR-247039

Q13131

P36956

1

phosphorylation

down-regulates activity

0.36

Ampk was recently found to phosphorylate a conserved serine near the cleavage site within srebp1, suppressing its activation

SIGNOR-176497

Q01581

P13674

0

transcriptional regulation

up-regulates quantity by expression

0.2

In this study, we found that the prolyl 4-hydroxylase (P4H) subunit P4HA1 protects NPC cells from erastin-induced ferroptosis by activating HMGCS1, a key enzyme in the mevalonate pathway. Our results show that HMGCS1 and HMGCR are regulated by P4HA subunits at the transcriptional level (Fig. S4).

SIGNOR-279853

P07949

Q9ULV8

0

ubiquitination

down-regulates quantity by destabilization

0.368

Here we show that Cbl-c binds wild-type and MEN2A isoforms of the receptor tyrosine kinase, RET, and that Cbl-c enhances ubiquitination and degradation of activated RET.|We show that Cbl-c negatively regulates RET by ubiquitinating and downregulating the activated RTK while Enigma positively regulates activated RET by preventing Cbl-c binding to RET and thus preventing RET ubiquitination and degradation while promoting RET mitogenic signaling.

SIGNOR-278674

Q9HAU4

Q15797

1

polyubiquitination

down-regulates quantity by destabilization

0.725

Here, we report the identification of Smurf2, a new member of the Hect family of E3 ubiquitin ligases. Smurf2 selectively interacts with receptor-regulated Smads and preferentially targets Smad1 for ubiquitination and proteasome-mediated degradation. At higher expression levels, Smurf2 also decreases the protein levels of Smad2, but not Smad3.

SIGNOR-272936

Q9NRM7

Q14872

1

phosphorylation

down-regulates activity

0.2

The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1|the Hippo pathway kinase LATS phosphorylates and inhibits MTF1|LATS phosphorylates MTF1 at S152 and disrupts its association with the promoters of heavy metal response genes, resulting in the loss of heavy metal response gene expression

SIGNOR-275475

Q9ULV8

P00533

1

polyubiquitination

down-regulates quantity by destabilization

0.761

In summary, we have shown that CBLC and AIP4 can interact and that these two E3 ligases could contribute to down-regulate EGFR signaling by ubiquitination.

SIGNOR-272605

P20749

P31749

0

phosphorylation

up-regulates quantity by stabilization

0.494

Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA.

SIGNOR-277358

Q13137

Q9UHD2

0

phosphorylation

up-regulates activity

0.795

Furthermore, we found that TBC1D9-regulated TBK1 activation and recruitment of NDP52 and ULK1 complex to damaged mitochondria (Fig.\u00a0 xref ).|TBK1 can phosphorylate p62, OPTN, and NDP52 to promote selective autophagy by facilitating their interaction with LC3, ubiquitin, and RAB35, respectively xref , xref , xref .

SIGNOR-280151

O75385

P09467

1

phosphorylation

down-regulates activity

0.2

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

SIGNOR-274031

Q7KZI7

Q8TEW0

1

phosphorylation

up-regulates

0.493

Gab1 brings par1 and par3 into a transient complex, stimulating par3 phosphorylation by par1

SIGNOR-198742

P53350

Q9NWD9

1

phosphorylation

up-regulates activity

0.2

In addition, the inhibition of PLK1 activity by BI2536 treatment sharply reduced BEX4 protein, which was localized at the centrosomes in the HeLa cells or the GFP-BEX4 stable cell lines.|PLK1 directly phosphorylates BEX4 at T107 and contributes to BEX4-induced aneuploidy.

SIGNOR-279550

P25874

Q7LBC6

0

transcriptional regulation

up-regulates quantity by expression

0.2

We show that Jhdm2a expression is induced by beta-adrenergic stimulation, and that Jhdm2a directly regulates peroxisome proliferator-activated receptor alpha (Ppara) and Ucp1 expression.

SIGNOR-266638

Q13158

O14733

0

phosphorylation

down-regulates activity

0.497

The results clearly show that fadd phosphorylation at ser194 affects functions both upstream and downstream of the mekk1/mkk7/jnk1 pathway and is closely associated with chemosensitivity in prostate cancer cells

SIGNOR-123164

Q9Y2U5

Q15208

1

phosphorylation

up-regulates quantity by stabilization

0.402

Our data suggest that Ser91 phosphorylation of STK38 by MEKK2 possibly blocks the interaction of calpain with STK38 or disrupts proper conformation for cleaving, thereby protecting STK38 from calpain-dependent degradation.

SIGNOR-279066

Q9H2X6

Q9NY61

1

phosphorylation

down-regulates quantity

0.346

HIPK2 phosphorylates Che-1.|Here we demonstrate that HIPK2, a proapoptotic kinase, is involved in Che-1 degradation.

SIGNOR-278942

Q9BSQ5

O00506

0

phosphorylation

up-regulates

0.5

CCM2 can be phosphorylated by STK25, and the kinase activity of STK25 is required for death signaling.

SIGNOR-263144

O14986

P43405

0

phosphorylation

down-regulates activity

0.2

We identified spleen tyrosine kinase (Syk), which is activated by oxidants, as a candidate PIP5Kbeta kinase in this pathway, and mapped the oxidant-sensitive tyrosine phosphorylation site to residue 105. The PIP5KbetaY105E phosphomimetic is catalytically inactive and cytosolic, whereas the Y105F non-phosphorylatable mutant has higher intrinsic lipid kinase activity and is much more membrane associated than wild type PIP5Kbeta.

SIGNOR-276227

Q15154

Q8N4C6

1

relocalization

up-regulates

0.406

Rna silencing of pcm-1 leads to reduced assembly of centrin, pericentrin, and ninein at the centrosome

SIGNOR-95077

P36888

P24752

1

phosphorylation

up-regulates activity

0.2

We previously reported that the mitochondrial fraction of FLT3 activates acetyl-CoA acetyltransferase ACAT1 in mitochondria via Y407 phosphorylation to acetylate and inhibit mitochondrial pyruvate dehydrogenase A (PDHA) and PDH phosphatase 1 (PDP1)

SIGNOR-267628

O95786

P55072

0

ubiquitination

down-regulates quantity by destabilization

0.2

Here, we report a new role for p97 with Npl4-Ufd1 as its cofactor in reducing antiviral innate immune responses by facilitating proteasomal degradation of RIG-I. The p97 complex is able to directly bind both non-ubiquitinated RIG-I and the E3 ligase RNF125, promoting K48-linked ubiquitination of RIG-I at residue K181.

SIGNOR-261000

P05546

P08311

0

cleavage

down-regulates activity

0.444

Amino acid sequence analysis led to the conclusion that both neutrophil elastase and cathepsin G cleave HC at Ile66, which does not affect HC activity, and at Val439, near the reactive site Leu444, which inactivates HC.

SIGNOR-256509

Q9UPZ9

Q8IZL9

0

phosphorylation

up-regulates

0.2

Recombinant cak1p phosphorylates thr-157 in the tdy motif of recombinant ick and activates its activity in vitro.

SIGNOR-138420

O15198

O00238

0

phosphorylation

up-regulates activity

0.708

Two types of bmp-induced signaling pathways are known, the smad and p38 mapk pathways. In the former case, bmpr1 phosphorylates smad-1,-5,-8, which forms a complex with smad4 that translocates into the nucleus and regulates gene expression.

SIGNOR-255264

O43462

P36956

1

cleavage

up-regulates activity

0.651

In order to activate transcription, the NH2-terminal domain of the SREBP must be released from the membrane so that it can enter the nucleus. This release has been studied most extensively for one of the SREBPs, namely, SREBP-2. However, the mechanism appears to be similar for the other SREBPs (SREBP-1a and -1c) (1). Release of the NH2-terminal domain is accomplished by a two-step proteolytic event that is regulated by sterols (3). In sterol-depleted mammalian cells, this proteolysis is initiated by the Site-1 protease (S1P), which cleaves human SREBP-2 between the Leu522-Ser523 bond in the sequence RSVL S (4). This cleavage requires formation of a complex between SREBP and SCAP, a polytopic membrane protein of the ER, and it is prevented when this complex is disrupted

SIGNOR-267499

P54646

Q9H2X6

1

phosphorylation

down-regulates activity

0.2

AMPKalpha2-mediated inhibition of WIP1 phosphorylation by HIPK2|Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKalpha2 in vitro

SIGNOR-275485

P29350

Q13114

1

dephosphorylation

down-regulates activity

0.2

We identified a direct interaction between SHP‐1 and TRAF3; the association between these two proteins resulted in diminished recruitment of CK1ε to TRAF3 and inhibited its K63‐linked ubiquitination; SHP‐1 inhibited K63‐linked ubiquitination of TRAF3 by promoting dephosphorylation at Tyr116 and Tyr446.

SIGNOR-277527

P06493

O00418

1

phosphorylation

down-regulates

0.368

Phosphorylation at ser359 inhibits eef2k activity even at high calcium concentrations. we demonstrate that cdc2 contributes to controlling eef2 phosphorylation in cells. inactivation of eef2k by cdc2 may serve to keep eef2 active during mitosis

SIGNOR-177982