GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
O15350	O14965	0	phosphorylation	down-regulates activity	0.449	Aurora-A inhibits p73 and p53 transactivation functions through a common molecular mechanism.\|We report that Aurora-A phosphorylation of p73 at serine235 abrogates its transactivation function and causes cytoplasmic sequestration in a complex with the chaperon protein mortalin.	SIGNOR-278263
Q15139	Q13936	1	phosphorylation	up-regulates	0.255	Both the expression of a dominant-negative mutant of pkd and the mutation of serine 1884 but not serine 1930, putative targets of pkd, strongly reduced l-type calcium currents and single channel activity without affecting the channel's expression at the plasma membrane. Our results suggest that serine 1884 is essential for the regulation of hcav1.2 by pkd.	SIGNOR-177481
Q13330	P78368	0	phosphorylation	up-regulates activity	0.344	CKI-gamma2 could further potentiate the ER corepressive function of metastasis-associated protein-1 short form.\|These findings identified metastasis-associated protein-1 short form as a target of CKI-gamma2, and provided new evidence to suggest that CKI-gamma2 phosphorylates and modulates the functions of metastasis-associated protein-1 short form, and that these extranuclear effects of estrogen might have important implications in regulating the functions of metastasis-associated protein-1 short form in human mammary epithelial and cancer cells.	SIGNOR-280236
P49841	Q86YF9	1	phosphorylation	up-regulates activity	0.39	Phosphorylation of Dzip1 by GSK3\u03b2 Promotes the Release of Rab8 GDP from GDI2.	SIGNOR-278251
Q92831	Q00987	0	ubiquitination	down-regulates quantity by destabilization	0.621	Consistently, overexpression of MDM2 in p53 null cells caused the reduction of the protein level of PCAF, but not the mRNA level.\|MDM2 ubiquitinated PCAF in vitro and in cells.	SIGNOR-278825
P62714	P01106	1	dephosphorylation	down-regulates	0.276	Phosphorylation at ser-62 by pro-directed kinases (p-k) is a prerequisite for gsk3-dependent phosphorylation of thr-58. This triggers binding of pin1, subsequently protein phosphatase 2a (pp2a)-dependent dephosphorylation of ser-62, and then recruitment of scf-fbw7 to the thr-58-phosphorylated myc. Scf-fbw7 polyubiquitinylates myc (branching through lys-48), leading to its proteasomal degradation.	SIGNOR-149726
P31946	O14920	0	phosphorylation	down-regulates	0.37	We provide a mechanism for these observations through the phosphorylation of 14-3-3beta by ikkbeta and pkcdelta on serine residues ser132 and ser60, respectively, which interferes with its binding to ttp and hence the retention of ttp in the cytoplasm.	SIGNOR-138608
Q96FX8	P19838	1	ubiquitination	down-regulates quantity	0.2	We identify KPC1 as the Ub ligase (E3) that binds to the ankyrin repeats domain of p105, ubiquitinates it, and mediates its processing both under basal conditions and following signaling	SIGNOR-255843
O95271	Q9H2G9	1	ADP-ribosylation	down-regulates quantity by destabilization	0.351	Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.	SIGNOR-263385
P03372	P28482	0	phosphorylation	up-regulates	0.671	In several estrogen response element-containing genes, the s118a mutation strongly reduced induction by e(2), and u0126 did not further reduce expression. Here, we show that serines 104 (s104) and 106 (s106) are also phosphorylated by mapk in vitro and upon stimulation of mapk activity in vivo.	SIGNOR-156856
Q07812	P99999	1	relocalization	up-regulates	0.699	The integration of bax oligomers in the outer mitochondrial membrane is followed by cytochrome crelease	SIGNOR-73898
Q08379	P62820	0	relocalization	up-regulates activity	0.718	Here, we demonstrate that the cis ‐Golgi tethering protein GM130, complexed with GRASP65 and other proteins, forms a novel Rab1 effector complex that interacts with activated Rab1‐GTP in a p115‐independent manner and is required for coat protein II vesicle targeting/fusion with the cis ‐Golgi	SIGNOR-261285
Q13315	P00533	0	phosphorylation	up-regulates activity	0.399	Here, we show that upon irradiation stimulation, ATM associates with and is phosphorylated by epidermal growth factor receptor (EGFR) at Tyr370 (Y370) at the site of DNA double-strand breaks.	SIGNOR-276872
Q15208	P53350	0	phosphorylation	down-regulates activity	0.316	Here, we identified a conserved signaling axis in which NDR1 kinase activity is regulated by PLK1 in mitosis. PLK1 phosphorylates NDR1 at three putative threonine residues (T7, T183 and T407) at mitotic entry, which elicits PLK1-dependent suppression of NDR1 activity and ensures correct spindle orientation in mitosis.	SIGNOR-276914
P42858	O00141	0	phosphorylation	down-regulates	0.372	The serum- and glucocorticoid-induced kinase sgk inhibits mutant huntingtin-induced toxicity by phosphorylating serine 421 of huntingtin.	SIGNOR-121349
Q8NBJ5	P08123	1	glycosylation	up-regulates activity	0.429	Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.	SIGNOR-261153
O43524	Q9HBY8	0	phosphorylation	down-regulates activity	0.521	Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a)\|However, SGK and Akt display differences with respect to the efficacy with which they phosphorylate the three regulatory sites on FKHRL1. While both kinases can phosphorylate Thr-32, SGK displays a marked preference for Ser-315 whereas Akt favors Ser-253. These findings suggest that SGK and Akt may coordinately regulate the function of FKHRL1 by phosphorylating this transcription factor at distinct sites. The efficient phosphorylation of these three sites on FKHRL1 by SGK and Akt appears to be critical to the ability of growth factors to suppress FKHRL1-dependent transcription, thereby preventing FKHRL1 from inducing cell cycle arrest and apoptosis.	SIGNOR-249130
P33981	P38646	1	phosphorylation	up-regulates	0.2	Mortalin binds to mps1, and is phosphorylated by mps1 on thr62 and ser65. The phosphorylated mortalin then super-activates mps1 in a feedback manner. Mps1-associated acceleration of centrosome duplication depends on the presence of mortalin and super-activation by the thr62/ser65 phosphorylated mortalin	SIGNOR-156185
Q6ZN28	O15075	0	phosphorylation	up-regulates activity	0.2	Subsequently, MACC1 gets phosphorylated by DCLK1.\|This might be attributed to the higher activation of MACC1 by DCLK1 in the MACC1-positive cell lines SW620/Control and SW480/MACC1 used in this study.	SIGNOR-279031
Q13470	P27448	0	phosphorylation	down-regulates activity	0.2	We also discover a MARK-mediated phosphorylation on TNK1 at S502 that promotes an interaction between TNK1 and 14-3-3, which sequesters TNK1 and inhibits its kinase activity.Phosphorylation of TNK1 at S502 within the proline rich domain is required for TNK1 binding to 14-3-3.MARKs mediate phosphorylation at S502 and 14-3-3 binding to TNK1, which restrains the movement of TNK1 into heavy membrane-associated clusters.	SIGNOR-273868
Q13586	Q9UGJ0	0	phosphorylation	down-regulates activity	0.2	STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE	SIGNOR-277297
P10721	P35222	1	phosphorylation	up-regulates activity	0.392	These results suggest that active KIT can directly phosphorylate tyrosine residues of beta-catenin.	SIGNOR-278361
Q92686	P05771	0	phosphorylation	up-regulates activity	0.361	Phosphorylation of RC3 by PKC alpha, beta, or gamma was stimulated by Ca2+, phospholipid, and diacylglycerol. A single site, Ser36, which is adjacent to the predicted calmodulin (CaM)-binding domain, was phosphorylated by these enzymes. Phosphorylation of RC3 by PKC or PKM, a protease-degraded PKC, was inhibited by CaM. The effect of CaM apparently targets at RC3, as phosphorylation of protamine sulfate by PKM was not inhibited by CaM.	SIGNOR-248914
P27361	Q9NYA1	1	phosphorylation	up-regulates	0.601	Activation of sphingosine kinase 1 by erk1/2-mediated phosphorylation.	SIGNOR-118550
Q00535	O94811	1	phosphorylation	down-regulates activity	0.403	Here we show that TPPP induces tubulin self-assembly into intact frequently bundled microtubules, and that the phosphorylation of specific sites distinctly affects the function of TPPP. The phosphorylation sites Thr(14), Ser(18), Ser(160) for Cdk5; Ser(18), Ser(160) for ERK2, and Ser(32) for PKA were identified by mass spectrometry. The phosphorylation by ERK2 or Cdk5 resulted in the loss of microtubule-assembling activity of TPPP.	SIGNOR-262931
Q13705	P84022	1	phosphorylation	up-regulates activity	0.69	It has been suggested that binding of myostatin to the ActRIIB results in the phosphorylation of two serine residues of Smad2 or Smad3 at COOH domains	SIGNOR-254985
Q9UQB3	Q00535	0	phosphorylation	up-regulates activity	0.327	Cdk5 mediated delta-catenin phosphorylation regulates delta-catenin subcellular localization into two distinct pools : a cytoplasmic or intraneurite state as well as a pool that is localized to the membrane.\|Cdk5 phosphorylates delta-catenin on serines 300 and 357.	SIGNOR-279323
O15530	P31751	1	phosphorylation	up-regulates activity	0.732	Akt1 and akt2 are phosphorylated and activated by the protein kinase pdk1 at thr-308 or thr-309, respectively, in the activation t-loop, and further activation occurs through phosphorylation at ser-473 or ser-474, respectively. Pdk1 phosphorylates akt-2 at thr 309 in the catalytic domain, leading to enzymatic activation.	SIGNOR-134485
Q07955	P49760	0	phosphorylation	up-regulates activity	0.298	In vitro, Clk/Sty efficiently phosphorylated the SR family member ASF/SF2 on serine residues located within its serine/arginine-rich region (the RS domain). Overexpression of the active Clk/Sty kinase caused a redistribution of SR proteins within the nucleus. These results suggest that Clk/Sty kinase directly regulates the activity and compartmentalization of SR splicing factors.	SIGNOR-273858
Q13761	P12931	0	phosphorylation	down-regulates activity	0.58	In this study, we provide evidence that Src phosphorylates RUNX3 at multiple tyrosine residues.\|Our finding that Src inactivates RUNX3 by cytoplasmic sequestration in gastric cancer and breast cancer suggests that the inactivation of RUNX3 may be a key function of oncogenic kinases.	SIGNOR-278199
Q9GZT9	P20042	0	translation regulation	up-regulates quantity	0.2	DAP5 is involved in PHD2 translation. Distinct responses to DAP5 depletion (under hypoxia) of primary MEFs versus malignant glioma cells suggest that DAP5-mediated control of PHD2 may have special significance in cancer. Neoplastic cells may exploit DAP5 for managing chronic oxygen deprivation, possibly contributing to their adaptation to growth/proliferation under hypoxia.	SIGNOR-266386
O60885	P62805	0	relocalization	up-regulates activity	0.2	BRD4 interacts with acetylated nucleosomes via both its BD1 and BD2 domains. Our results indicate that BRD4-BD1 binds to nucleosomes through the acetylated histone H4 tail and does not additionally interact with DNA.	SIGNOR-262065
O43164	P10644	1	polyubiquitination	down-regulates quantity by destabilization	0.379	Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits	SIGNOR-271855
P17275	Q96J02	0	polyubiquitination	down-regulates quantity by destabilization	0.408	Itch promotes Ub conjugation to JunB Molecularly, Itch associated with and induced ubiquitination of JunB, a transcription factor that is involved in TH2 differentiation. However, in Itch−/− T cells under the same conditions, degradation of JunB was markedly delayed.	SIGNOR-272619
P67870	Q92915	1	phosphorylation	up-regulates activity	0.27	Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents.	SIGNOR-275745
P23760	P15056	0	phosphorylation	up-regulates activity	0.308	BRAF activates PAX3 to control muscle precursor cell migration during forelimb muscle development.\|We found that BRAF clearly induced phosphorylation of PAX3 at Ser205 in both cell types (XREF_FIG).	SIGNOR-278435
P00519	Q9BX66	1	phosphorylation	up-regulates activity	0.424	We have here identified Tyr360 in CAP as a major phosphorylation site by c-Abl, although Tyr 632 also might contribute since its substitution in combination with the Y360F mutation reduced the phosphorylation of CAP to a very low level. Y360 in CAP is the major phosphorylation site of c-Abl. Since Tyr326 was not a major c-Abl phosphorylation site, we sought to identify a putative other kinase that might be involved in the phosphorylation of Y326 in CAP.	SIGNOR-278153
Q92886	Q13164	0	phosphorylation	up-regulates activity	0.35	Activation of ERK5 potentiates while inhibition of ERK5 attenuates Neurog1 stimulated neurogenesis.\|ERK5 directly phosphorylated Neurog1 in vitro and modulated the transcriptional and pro-neural activity of Neurog1 in cortical progenitors.	SIGNOR-278364
P05771	Q5T7P8	1	phosphorylation	up-regulates activity	0.2	We found by site-directed mutagenesis that Thr418 and/or Thr419 in the polybasic region (KKKTTIK) of the C2B domain--a key region for the function of synaptotagmins--are the PKC target that regulates its inhibitory effect on acrosomal exocytosis. Similarly, we showed that Thr284 in the polybasic region of C2A (KCKLQTR) is the target for PKC-mediated phosphorylation in this domain.	SIGNOR-273565
Q96BR1	O43524	1	phosphorylation	down-regulates activity	0.435	Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a)\|However, SGK and Akt display differences with respect to the efficacy with which they phosphorylate the three regulatory sites on FKHRL1. While both kinases can phosphorylate Thr-32, SGK displays a marked preference for Ser-315 whereas Akt favors Ser-253. These findings suggest that SGK and Akt may coordinately regulate the function of FKHRL1 by phosphorylating this transcription factor at distinct sites. The efficient phosphorylation of these three sites on FKHRL1 by SGK and Akt appears to be critical to the ability of growth factors to suppress FKHRL1-dependent transcription, thereby preventing FKHRL1 from inducing cell cycle arrest and apoptosis.	SIGNOR-249135
Q9UQM7	Q86UR5	1	phosphorylation	up-regulates	0.347	Two serine residues in rim1 (ser-241 and ser-287) and one serine residue in rim2 (ser-335) were required for 14-3-3 binding. Incubation with ca2+/calmodulin-dependent protein kinase ii greatly stimulated the interaction of recombinant n-terminal rim but not the s241/287a mutant with 14-3-3,	SIGNOR-103890
Q13148	P00519	0	phosphorylation	up-regulates quantity	0.2	The phosphorylation of tyrosine 43 of TDP-43 by c-Abl led to increased TDP-43 levels in the cytoplasm and increased the formation of G3BP1-positive stress granules in SH-SY5Y cells.	SIGNOR-279135
Q9NZV8	P28482	0	phosphorylation	up-regulates activity	0.367	We determined that the Kv4.2 C-terminal cytoplasmic domain is an effective ERK2 substrate, and that it is phosphorylated at three sites: Thr(602), Thr(607), and Ser(616). Phosphorylation of the Kv4.2 channel by ERK during LTP induction may lead to increased excitability and membrane depolarization of neurons, which would increase the magnitude of the calcium influx and the probability of triggering LTP.	SIGNOR-262935
P06744	O15297	0	dephosphorylation	down-regulates activity	0.24	The WIP1 mediated inhibition of NLK activity markedly decreased the phosphorylation of lymphoid enhancer binding factor 1 (LEF1), enhancing its interaction with beta-catenin.\|Wip1 directly dephosphorylates NLK and increases Wnt activity during germ cell development.	SIGNOR-277155
Q9Y4P1	P60520	1	cleavage	up-regulates activity	0.844	In mammals, at least three atg8 homologs, lc3, gabarap, and gate-16, have been identified (fig. 1a), all of which have structural ubiquitin folds (1416). In vivo and in vitro biochemical analyses have shown that human atg4b is an authentic cysteine protease essential for cleavage of the c terminus of each atg8 homolog to expose the c-terminal gly	SIGNOR-141932
P18545	P25098	0	phosphorylation	up-regulates activity	0.2	Mutation of Thr-62 (to Ala) in PDEgamma produced a GRK2 phosphorylation-resistant mutant that was less effective in associating with GRK2 in response to epidermal growth factor and did not potentiate the stimulation of p42/p44 mitogen-activated protein kinase by this growth factor.	SIGNOR-247823
P28482	O00141	0	phosphorylation	up-regulates activity	0.309	SGK1 was found to physically interact with ERK1/2 as well as MEK1/2. Furthermore, SGK1 mediated the phosphorylation of ERK2 on Ser(29) in a serum-dependent manner. Replacement of Ser(29) to aspartic acid, which mimics the phosphorylation of Ser(29), enhanced the ERK2 activity as well as the MEK/ERK complexes formation.	SIGNOR-276223
P27707	P48730	0	phosphorylation	up-regulates activity	0.339	Site-directed mutagenesis demonstrated that only Ser-74 phosphorylation was involved in Deoxycytidine kinase activation by CKI delta, strengthening the key role of this residue in the control of Deoxycytidine kinase activity.\|We showed that recombinant CKI delta phosphorylated several residues of bacterially overexpressed Deoxycytidine kinase: Ser-74, but also Ser-11, Ser-15, and Thr-72.	SIGNOR-280233
O14529	Q8TE12	0	transcriptional regulation	up-regulates quantity by expression	0.285	Lmx1a drives Cux2 expression in the cortical hem through activation of a conserved intronic enhancer. Lmx1a knockdown abolishes activation of the Cux2 enhancer in the cortical hem	SIGNOR-263961
Q8WU20	P11362	0	phosphorylation	up-regulates activity	0.867	As shown in xref , wild type FGFR1c phosphorylated FRS2\u03b1 on tyrosine 196 whereas the V429E mutant did not.	SIGNOR-280013
P55265	P31751	0	phosphorylation	down-regulates activity	0.2	AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively	SIGNOR-276192
P08908	O75398	0	transcriptional regulation	down-regulates quantity by repression	0.437	The human 5-HT1A gene (HTR1A) rs6295 risk allele prevents Deaf1 binding to HTR1A, resulting in increased 5-HT1A autoreceptor transcription	SIGNOR-269064
P45983	P42224	1	phosphorylation	up-regulates activity	0.445	SP600125 prevented phosphorylation of STAT1 at Tyr701 site [..] Western blot analysis confirmed that blocking p-JNK using SP600125 markedly reduced STAT3 localization in the nucleus and STAT1 phosphorylation	SIGNOR-251101
Q00535	Q96PV0	1	phosphorylation	up-regulates activity	0.383	CDK5 increases recombinant SYNGAP1 activity on Ras-GAP by 98% and its Rap-GAP activity by 20%.\|Interestingly, phosphorylation of SYNGAP1 by CDK5 and CaMKII increases overall SYNGAP1 activity, but also alters the ratio of its GAP activity towards Ras- and Rap-GTPases.	SIGNOR-279157
Q13158	Q9H422	0	phosphorylation	down-regulates activity	0.436	FIST/HIPK3 causes FADD phosphorylation, thereby promoting FIST/HIPK3-FADD-Fas interaction.¬† Phosphorylation occurs on Ser194 close to the COOH terminus of human FADD\| Fas ligand-induced activation of Jun NH(2)-terminal kinase is impaired by overexpressed active FIST/HIPK3	SIGNOR-251272
Q13535	P16220	1	phosphorylation	down-regulates	0.347	Atm phosphorylated creb in vitro and in vivo in response to ionizing radiation (ir) and h(2)o(2) on a stress-inducible domain. Ir-induced phosphorylation of creb correlated with a decrease in creb transactivation potential and reduced interaction between creb and its transcriptional coactivator, creb-binding protein (cbp). A creb mutant containing ala substitutions at atm phosphorylation sites displayed enhanced transactivation potentialit is, therefore, likely that atm and atr regulate creb phosphorylation collectively in response to stress stimuli.	SIGNOR-124060
P53350	P12830	1	phosphorylation	down-regulates quantity by destabilization	0.297	Priming phosphorylation of Cdh1 by the Cdk2/cyclin A kinase complex allows Plk1 to bind to Cdh1 and phosphorylate Cdh1 at Ser138 and Ser146. Phosphorylation of Cdh1 at Ser138 and Ser146 then triggers its interaction with, and subsequent ubiquitination by, SCFbeta-TRCP	SIGNOR-274054
Q9UJU2	P19883	1	transcriptional regulation	up-regulates quantity by expression	0.28	We further demonstrate that Fst is a direct target of the WNT/β-catenin pathway. Activation and inactivation of β-catenin induced and inhibited Fst expression, respectively, in both C2C12 cells and mouse embryos. Specific TCF/LEF1 binding sites within the promoter and intron 1 region of the Fst gene were required for RSPO2 and WNT/β-catenin-induced Fst expression.	SIGNOR-251722
P01019	Q9BYF1	0	cleavage	up-regulates activity	0.759	The ACE2 hydrolytic activity is dependent on the C terminus sequence of the substrate, which is evident from the data with the angiotensin peptides. After 2 h, ACE2 hydrolyzes Ang I partially and Ang II completely, although there is no hydrolysis of angiotensin 1–9, angiotensin 1–7, and angiotensin 1–5, which possess the same N terminus.	SIGNOR-256315
Q13535	P54132	1	phosphorylation	up-regulates activity	0.852	It is noteworthy that an active BLM seems to be unnecessary to the activation of BRCA1, either after gamma-rays or HU, even though BRCA1 and BLM helicase are activated by ATR in response to stalled replication, and despite the fact that they colocalize after replication arrest.\|These results show that BLM phosphorylation by ATR after replication fork arrest is not important for its relocalization.	SIGNOR-278978
O14920	Q99558	0	phosphorylation	up-regulates	0.714	Activation of the transcription factor nf-kappab by inflammatory cytokines involves the successive action of nf-kappab-inducing kinase (nik) and two ikappab kinases, ikk-alpha and ikk-beta. Here we show that nik preferentially phosphorylates ikk-alpha over ikk-beta	SIGNOR-55949
Q13291	P06241	0	phosphorylation	up-regulates activity	0.658	All 3 tyrosines of CD150 (Tyr281, Tyr307, Tyr327) are phosphorylated by the src kinase Fyn. CD150 is unique among its homologues in the immunoglobulin superfamily in that it is able to bind SAP, a floating SH2 domain, in the absence of tyrosine phosphorylation. In this study, using a detailed mutagenesis mapping approach we have shown that SAP binding to CD150 is in fact bimodal. Prior to tyrosine phosphorylation, SAP binds the membrane-proximal motif surrounding Tyr281. Following tyrosine phosphorylation by tyrosine kinases such as Fyn, SAP binds additionally to the distal motif surrounding Tyr327.	SIGNOR-251182
Q15418	P27361	0	phosphorylation	up-regulates activity	0.718	Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity.Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3.	SIGNOR-102648
Q9P2P5	Q8IY63	1	ubiquitination	up-regulates activity	0.419	These results clearly indicate that HECW2 ubiquitinates AMOTL1 with K63-linked polyubiquitin chains.\|Unlike NEDD4.2, HECW2 targeted AMOTL1 and promoted its stability.	SIGNOR-278811
Q9GZU1	P17612	0	phosphorylation	down-regulates	0.2	The stimulatory effect of h89 on mcoln1 function was not observed when ser(557) and ser(559) were mutated to alanine residues, indicating that these two residues are essential for pka-mediated negative regulation of mcoln1.	SIGNOR-158946
P08235	P34947	0	phosphorylation	down-regulates	0.26	We report that GRK5 phosphorylates and inhibits the cardiac MR whereas GRK2 phosphorylates and desensitizes GPER.	SIGNOR-278478
O75688	Q13627	1	dephosphorylation	down-regulates activity	0.236	In conclusion, our study demonstrates that DYRK1A autophosphorylates Ser258, the dephosphorylation target of PPM1B, and PPM1B negatively regulates DYRK1A activity.\|We found that PPM1B dephosphorylates DYRK1A at Ser258, contributing to the inhibition of DYRK1A activity.	SIGNOR-277108
Q15418	Q15653	1	phosphorylation	down-regulates quantity by destabilization	0.369	By using recombinant wild-type and mutant IkappaBbeta proteins, both active ERK2 and RSK1 were found to directly phosphorylate IkappaBbeta, but only active RSK1 phosphorylated IkappaBbeta on Ser19 and Ser23, two sites known to mediate the subsequent ubiquitination and degradation.	SIGNOR-280114
P61586	O14827	0	guanine nucleotide exchange factor	up-regulates activity	0.553	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260573
P63000	P10911	0	guanine nucleotide exchange factor	up-regulates activity	0.665	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260557
P20963	Q9Y2R2	0	dephosphorylation	down-regulates activity	0.447	In vitro experiments with purified recombinant proteins demonstrated that PTPN22-D195A/C227S interacted directly with activated Lck, Zap70, and TCRzeta, confirming the initial substrate trap results. Native PTPN22 dephosphorylated Lck and Zap70 at their activating tyrosine residues Tyr-394 and Tyr-493, respectively, but not at the regulatory tyrosines Tyr-505 (Lck) or Tyr-319 (Zap70). Native PTPN22 also dephosphorylated TCRzeta in vitro and in cells, and its substrate trap variant co-immunoprecipitated with TCRzeta when both were coexpressed in 293T cells, establishing TCRzeta as a direct substrate of PTPN22.	SIGNOR-248837
P55157	P04114	1	lipidation	up-regulates activity	0.793	As ApoB is translated, it is lipidated by microsomal triglyceride transfer protein (MTP). MTP adds triglycerides to the nascent ApoB during its co-translational translocation into the lumen of the endoplasmic reticulum.	SIGNOR-252118
Q13541	P42345	0	phosphorylation	down-regulates activity	0.926	Specifically as part of mTORC1, mTOR directly phosphorylates the ribo- somal protein S6 kinases (S6K1 and S6K2) and the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BP1 and 4E-BP2), both of which control specific steps in the initiation of cap-dependent translation	SIGNOR-167184
Q15797	Q13315	0	phosphorylation	up-regulates	0.2	On genotoxic stress, atm phosphorylates bmps-activated smad1 in the nucleus on s239, which disrupts smad1 interaction with protein phosphatase ppm1a, leading to enhanced activation and upregulation of smad1.	SIGNOR-197533
Q9H4B4	O15350	1	phosphorylation	down-regulates activity	0.41	In this study, we found that Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation.\|Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation.	SIGNOR-279647
P42772	Q92560	0	transcriptional regulation	up-regulates quantity by expression	0.2	Since we found that ASXL1 and BAP1 both are enriched at the INK4B locus, our results suggest that activation of the INK4B locus requires ASXL1/BAP1-mediated deubiquitinylation of H2AK119ub1.	SIGNOR-241656
P49841	P31749	0	phosphorylation	down-regulates activity	0.792	Active AKT, a common mediator of cell survival signals induced by radiation through multiple intracellular signaling pathways,11, 12 suppresses apoptosis. AKT positively regulates cyclin D1 expression through inactivation of glycogen synthase kinase 3beta (GSK3B). The AKT-mediated phosphorylation of glycogen synthase kinase 3b on serine9 decreases its kinase activity for Thr286 of cyclin D1, which inhibits the nuclear export and the cytoplasmic proteasomal degradation of cyclin D1	SIGNOR-245416
P12931	P03372	1	phosphorylation	up-regulates	0.778	Although the molecular mechanisms underlying ligand-independent activation of era are not completely understood, phosphorylation of a serine residue in af1 has been implicated in the response to epidermal growth factor. Era is also a target for tyrosine phosphorylation, anda single tyrosine residue located immediately adjacent to af2 has been identified as a substrate for src-family tyrosine kinases.	SIGNOR-55857
Q92934	P45983	0	phosphorylation	down-regulates	0.686	Jnk phosphorylates bad at threonine 201, thereby inhibiting bad association with the antiapoptotic molecule bcl-x(l)	SIGNOR-121940
Q13043	Q15208	1	phosphorylation	up-regulates activity	0.332	Although MST1, MST2, and MST3 potently activated NDR1 in vitro, MST4 had only a minor effect.\|Indeed, NDR1 phosphorylated at Thr444 by MST1 displayed greatly (7-fold) enhanced protein kinase activity.	SIGNOR-279641
P68400	Q9H257	1	phosphorylation	down-regulates activity	0.346	PVHL Acts as an Adaptor to Promote the Inhibitory Phosphorylation of the NF-κB Agonist Card9 by CK2	SIGNOR-257601
P05129	P28329	1	phosphorylation	up-regulates	0.321	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-129320
Q9BW92	Q2TAL8	0	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269407
Q13315	P41236	1	phosphorylation	down-regulates	0.2	Atm phosphorylates i-2 on serine 43, leading to the dissociation of the pp1-i-2 complex and the activation of pp1.	SIGNOR-160648
P04049	Q13131	0	phosphorylation	down-regulates	0.342	Ampk also phosphorylated full-length, kinase-defective raf-1 (k375m) to generate two [32p]phosphopeptides, one co-migrating with synthetic tryptic peptide containing phospho-ser621 and the other with phospho-ser259. The catalytic subunit of PKA also phosphorylated Ser621 in vitro, while its overexpression in intact cells resulted in increased phosphorylation of Ser621 and decreased activity of Raf-1. These results suggest that phosphorylation of Ser621 inactivates Raf-1, but do not prove that PKA is responsible for this in vivo.	SIGNOR-47148
P48431	Q9UGL1	0	transcriptional regulation	down-regulates quantity by repression	0.309	Phosphorylation of KDM5B at Ser1456 attenuated the occupancy of KDM5B on the promoters of pluripotency genes.	SIGNOR-273450
P35236	P24723	0	phosphorylation	up-regulates activity	0.2	HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.	SIGNOR-276049
Q96GD4	Q8NEM2	1	phosphorylation	up-regulates activity	0.372	AurB phosphorylates Ser634 of SHCBP1 during mitosis. We generated a phosphorylation site mutant, S634A-SHCBP1, which was prematurely recruited to the central spindle during anaphase and inhibited furrowing.	SIGNOR-273552
P06213	P0DP24	1	phosphorylation	down-regulates	0.352	The in vitro phosphorylation of calmodulin by the insulin receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.	SIGNOR-266320
P08588	Q9HD26	0	relocalization	down-regulates	0.342	Overexpression of cal reduces surface expression of beta1ar. Interaction with cal promotes retention of beta1ar within the cell	SIGNOR-128791
Q9UNE7	P56545	1	ubiquitination	down-regulates quantity by destabilization	0.331	Our data showed that CHIP depletion resulted in up-regulation of the steady-state level of CtBP2 ( Fig. 1 B) and that CHIP ubiquitinated CtBP2 for proteasomal degradation ( Fig. 3 A).	SIGNOR-278722
P24941	Q86WB0	1	phosphorylation	down-regulates	0.2	Moreover, we found cyclin b1/cdk1 to phosphorylate nipa at ser-395 in mitosis. Mutation of both ser-359 and ser-395 impaired effective inactivation of the scfnipa complex, resulting in reduced levels of mitotic cyclin b1	SIGNOR-154051
Q13315	Q02880	1	phosphorylation	down-regulates quantity by destabilization	0.411	Specifically, DNA damage signal, triggered by teniposide (VM-26) treatment, activates ATM, cooperating with CK1 to phosphorylate TOP2β on Ser1134 and Ser1130, respectively, in a canonical degron motif to facilitate β-TrCP binding and subsequent degradation.ATM binds with and phosphorylates TOP2β at Ser1134 to promote its degradation by VM-26.	SIGNOR-277510
Q13683	P15172	0	transcriptional regulation	up-regulates quantity by expression	0.286	Only myogenin and MyoD were able to efficiently trans-activate the alpha7 promoter-CAT construct (Fig. 7). Myogenin trans-activated the promoter by _2-fold whereas MyoD was able to trans-activate by nearly 4-fold, indicating that both of these factors may play a role in alpha7 gene expression during muscle development.	SIGNOR-241518
Q00653	P49841	0	phosphorylation	down-regulates activity	0.271	More recently, phosphorylation of S707 and S711 by GSK3beta has been shown to promote complete proteasomal degradation of p100 involving the E3 ligase Fbw7 .\|These studies suggest that a pool of p100 is constitutively phosphorylated by GSK3beta at S707 and S711, triggering the Fbw7 mediated ubiquitination and proteasomal degradation of p100 which controls the levels of p100 available for the non canonical pathway.	SIGNOR-279186
P01903	Q5T0T0	0	polyubiquitination	down-regulates quantity by destabilization	0.2	Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination.	SIGNOR-271411
P18846	Q13362	0	dephosphorylation	up-regulates	0.2	We propose that constitutive hyperphosphorylation by ck1/ck2 maintains atf1 in an inactive state that promotes transcriptional repression. Pp2a/b56c antagonizes phosphorylation of atm sites in both creb and atf5	SIGNOR-167564
P22888	P49116	0	transcriptional regulation	up-regulates quantity by expression	0.2	Functional analysis showed that EAR2 and EAR3/COUP-TFI repressed the hLHR promoter activity, whereas TR4 activated hLHR gene transcription.	SIGNOR-266217
P08034	P17252	0	phosphorylation	up-regulates activity	0.362	Phosphorylation of connexin-32 by protein kinase C prevents its proteolysis by mu-calpain and m-calpain. \|In agreement with other authors (see Saez et al., 1990b), we have found that phosphorylation of connexin-32 by protein kinase A and protein kinase C occurs in serine residues, although we have detected trace amounts of phosphothreonine in connexin-32 phosphorylated by protein kinase C (results not shown). Indeed, Se233 has been shown to be the major phosphorylation site catalyzed by protein kinase A. However, Ser233, Ser239, and perhaps other serines are phosphorylated by protein kinase C (Saez et al., 1990b).	SIGNOR-248919
Q9H3D4	Q15149	1	transcriptional regulation	up-regulates quantity by expression	0.2	Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by a marked decrease in expression of several nuclear envelope-associated components (Lamin B1, Lamin A/C, Sun1, Nesprin-3, Plectin) compared with controls. Furthermore, chromatin immunoprecipitation-quantitative PCR assay showed enrichment of p63 on Sun1, Syne3, and Plec promoters, suggesting them as p63 targets.	SIGNOR-263279

O15350

O14965

0

phosphorylation

down-regulates activity

0.449

Aurora-A inhibits p73 and p53 transactivation functions through a common molecular mechanism.|We report that Aurora-A phosphorylation of p73 at serine235 abrogates its transactivation function and causes cytoplasmic sequestration in a complex with the chaperon protein mortalin.

SIGNOR-278263

Q15139

Q13936

1

phosphorylation

up-regulates

0.255

Both the expression of a dominant-negative mutant of pkd and the mutation of serine 1884 but not serine 1930, putative targets of pkd, strongly reduced l-type calcium currents and single channel activity without affecting the channel's expression at the plasma membrane. Our results suggest that serine 1884 is essential for the regulation of hcav1.2 by pkd.

SIGNOR-177481

Q13330

P78368

0

phosphorylation

up-regulates activity

0.344

CKI-gamma2 could further potentiate the ER corepressive function of metastasis-associated protein-1 short form.|These findings identified metastasis-associated protein-1 short form as a target of CKI-gamma2, and provided new evidence to suggest that CKI-gamma2 phosphorylates and modulates the functions of metastasis-associated protein-1 short form, and that these extranuclear effects of estrogen might have important implications in regulating the functions of metastasis-associated protein-1 short form in human mammary epithelial and cancer cells.

SIGNOR-280236

P49841

Q86YF9

1

phosphorylation

up-regulates activity

0.39

Phosphorylation of Dzip1 by GSK3\u03b2 Promotes the Release of Rab8 GDP from GDI2.

SIGNOR-278251

Q92831

Q00987

0

ubiquitination

down-regulates quantity by destabilization

0.621

Consistently, overexpression of MDM2 in p53 null cells caused the reduction of the protein level of PCAF, but not the mRNA level.|MDM2 ubiquitinated PCAF in vitro and in cells.

SIGNOR-278825

P62714

P01106

1

dephosphorylation

down-regulates

0.276

Phosphorylation at ser-62 by pro-directed kinases (p-k) is a prerequisite for gsk3-dependent phosphorylation of thr-58. This triggers binding of pin1, subsequently protein phosphatase 2a (pp2a)-dependent dephosphorylation of ser-62, and then recruitment of scf-fbw7 to the thr-58-phosphorylated myc. Scf-fbw7 polyubiquitinylates myc (branching through lys-48), leading to its proteasomal degradation.

SIGNOR-149726

P31946

O14920

0

phosphorylation

down-regulates

0.37

We provide a mechanism for these observations through the phosphorylation of 14-3-3beta by ikkbeta and pkcdelta on serine residues ser132 and ser60, respectively, which interferes with its binding to ttp and hence the retention of ttp in the cytoplasm.

SIGNOR-138608

Q96FX8

P19838

1

ubiquitination

down-regulates quantity

0.2

We identify KPC1 as the Ub ligase (E3) that binds to the ankyrin repeats domain of p105, ubiquitinates it, and mediates its processing both under basal conditions and following signaling

SIGNOR-255843

O95271

Q9H2G9

1

ADP-ribosylation

down-regulates quantity by destabilization

0.351

Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.

SIGNOR-263385

P03372

P28482

0

phosphorylation

up-regulates

0.671

In several estrogen response element-containing genes, the s118a mutation strongly reduced induction by e(2), and u0126 did not further reduce expression. Here, we show that serines 104 (s104) and 106 (s106) are also phosphorylated by mapk in vitro and upon stimulation of mapk activity in vivo.

SIGNOR-156856

Q07812

P99999

1

relocalization

up-regulates

0.699

The integration of bax oligomers in the outer mitochondrial membrane is followed by cytochrome crelease

SIGNOR-73898

Q08379

P62820

0

relocalization

up-regulates activity

0.718

Here, we demonstrate that the cis ‐Golgi tethering protein GM130, complexed with GRASP65 and other proteins, forms a novel Rab1 effector complex that interacts with activated Rab1‐GTP in a p115‐independent manner and is required for coat protein II vesicle targeting/fusion with the cis ‐Golgi

SIGNOR-261285

Q13315

P00533

0

phosphorylation

up-regulates activity

0.399

Here, we show that upon irradiation stimulation, ATM associates with and is phosphorylated by epidermal growth factor receptor (EGFR) at Tyr370 (Y370) at the site of DNA double-strand breaks.

SIGNOR-276872

Q15208

P53350

0

phosphorylation

down-regulates activity

0.316

Here, we identified a conserved signaling axis in which NDR1 kinase activity is regulated by PLK1 in mitosis. PLK1 phosphorylates NDR1 at three putative threonine residues (T7, T183 and T407) at mitotic entry, which elicits PLK1-dependent suppression of NDR1 activity and ensures correct spindle orientation in mitosis.

SIGNOR-276914

P42858

O00141

0

phosphorylation

down-regulates

0.372

The serum- and glucocorticoid-induced kinase sgk inhibits mutant huntingtin-induced toxicity by phosphorylating serine 421 of huntingtin.

SIGNOR-121349

Q8NBJ5

P08123

1

glycosylation

up-regulates activity

0.429

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

SIGNOR-261153

O43524

Q9HBY8

0

phosphorylation

down-regulates activity

0.521

Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a)|However, SGK and Akt display differences with respect to the efficacy with which they phosphorylate the three regulatory sites on FKHRL1. While both kinases can phosphorylate Thr-32, SGK displays a marked preference for Ser-315 whereas Akt favors Ser-253. These findings suggest that SGK and Akt may coordinately regulate the function of FKHRL1 by phosphorylating this transcription factor at distinct sites. The efficient phosphorylation of these three sites on FKHRL1 by SGK and Akt appears to be critical to the ability of growth factors to suppress FKHRL1-dependent transcription, thereby preventing FKHRL1 from inducing cell cycle arrest and apoptosis.

SIGNOR-249130

P33981

P38646

1

phosphorylation

up-regulates

0.2

Mortalin binds to mps1, and is phosphorylated by mps1 on thr62 and ser65. The phosphorylated mortalin then super-activates mps1 in a feedback manner. Mps1-associated acceleration of centrosome duplication depends on the presence of mortalin and super-activation by the thr62/ser65 phosphorylated mortalin

SIGNOR-156185

Q6ZN28

O15075

0

phosphorylation

up-regulates activity

0.2

Subsequently, MACC1 gets phosphorylated by DCLK1.|This might be attributed to the higher activation of MACC1 by DCLK1 in the MACC1-positive cell lines SW620/Control and SW480/MACC1 used in this study.

SIGNOR-279031

Q13470

P27448

0

phosphorylation

down-regulates activity

0.2

We also discover a MARK-mediated phosphorylation on TNK1 at S502 that promotes an interaction between TNK1 and 14-3-3, which sequesters TNK1 and inhibits its kinase activity.Phosphorylation of TNK1 at S502 within the proline rich domain is required for TNK1 binding to 14-3-3.MARKs mediate phosphorylation at S502 and 14-3-3 binding to TNK1, which restrains the movement of TNK1 into heavy membrane-associated clusters.

SIGNOR-273868

Q13586

Q9UGJ0

0

phosphorylation

down-regulates activity

0.2

STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE

SIGNOR-277297

P10721

P35222

1

phosphorylation

up-regulates activity

0.392

These results suggest that active KIT can directly phosphorylate tyrosine residues of beta-catenin.

SIGNOR-278361

Q92686

P05771

0

phosphorylation

up-regulates activity

0.361

Phosphorylation of RC3 by PKC alpha, beta, or gamma was stimulated by Ca2+, phospholipid, and diacylglycerol. A single site, Ser36, which is adjacent to the predicted calmodulin (CaM)-binding domain, was phosphorylated by these enzymes. Phosphorylation of RC3 by PKC or PKM, a protease-degraded PKC, was inhibited by CaM. The effect of CaM apparently targets at RC3, as phosphorylation of protamine sulfate by PKM was not inhibited by CaM.

SIGNOR-248914

P27361

Q9NYA1

1

phosphorylation

up-regulates

0.601

Activation of sphingosine kinase 1 by erk1/2-mediated phosphorylation.

SIGNOR-118550

Q00535

O94811

1

phosphorylation

down-regulates activity

0.403

Here we show that TPPP induces tubulin self-assembly into intact frequently bundled microtubules, and that the phosphorylation of specific sites distinctly affects the function of TPPP. The phosphorylation sites Thr(14), Ser(18), Ser(160) for Cdk5; Ser(18), Ser(160) for ERK2, and Ser(32) for PKA were identified by mass spectrometry. The phosphorylation by ERK2 or Cdk5 resulted in the loss of microtubule-assembling activity of TPPP.

SIGNOR-262931

Q13705

P84022

1

phosphorylation

up-regulates activity

0.69

It has been suggested that binding of myostatin to the ActRIIB results in the phosphorylation of two serine residues of Smad2 or Smad3 at COOH domains

SIGNOR-254985

Q9UQB3

Q00535

0

phosphorylation

up-regulates activity

0.327

Cdk5 mediated delta-catenin phosphorylation regulates delta-catenin subcellular localization into two distinct pools : a cytoplasmic or intraneurite state as well as a pool that is localized to the membrane.|Cdk5 phosphorylates delta-catenin on serines 300 and 357.

SIGNOR-279323

O15530

P31751

1

phosphorylation

up-regulates activity

0.732

Akt1 and akt2 are phosphorylated and activated by the protein kinase pdk1 at thr-308 or thr-309, respectively, in the activation t-loop, and further activation occurs through phosphorylation at ser-473 or ser-474, respectively. Pdk1 phosphorylates akt-2 at thr 309 in the catalytic domain, leading to enzymatic activation.

SIGNOR-134485

Q07955

P49760

0

phosphorylation

up-regulates activity

0.298

In vitro, Clk/Sty efficiently phosphorylated the SR family member ASF/SF2 on serine residues located within its serine/arginine-rich region (the RS domain). Overexpression of the active Clk/Sty kinase caused a redistribution of SR proteins within the nucleus. These results suggest that Clk/Sty kinase directly regulates the activity and compartmentalization of SR splicing factors.

SIGNOR-273858

Q13761

P12931

0

phosphorylation

down-regulates activity

0.58

In this study, we provide evidence that Src phosphorylates RUNX3 at multiple tyrosine residues.|Our finding that Src inactivates RUNX3 by cytoplasmic sequestration in gastric cancer and breast cancer suggests that the inactivation of RUNX3 may be a key function of oncogenic kinases.

SIGNOR-278199

Q9GZT9

P20042

0

translation regulation

up-regulates quantity

0.2

DAP5 is involved in PHD2 translation. Distinct responses to DAP5 depletion (under hypoxia) of primary MEFs versus malignant glioma cells suggest that DAP5-mediated control of PHD2 may have special significance in cancer. Neoplastic cells may exploit DAP5 for managing chronic oxygen deprivation, possibly contributing to their adaptation to growth/proliferation under hypoxia.

SIGNOR-266386

O60885

P62805

0

relocalization

up-regulates activity

0.2

BRD4 interacts with acetylated nucleosomes via both its BD1 and BD2 domains. Our results indicate that BRD4-BD1 binds to nucleosomes through the acetylated histone H4 tail and does not additionally interact with DNA.

SIGNOR-262065

O43164

P10644

1

polyubiquitination

down-regulates quantity by destabilization

0.379

Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits

SIGNOR-271855

P17275

Q96J02

0

polyubiquitination

down-regulates quantity by destabilization

0.408

Itch promotes Ub conjugation to JunB Molecularly, Itch associated with and induced ubiquitination of JunB, a transcription factor that is involved in TH2 differentiation. However, in Itch−/− T cells under the same conditions, degradation of JunB was markedly delayed.

SIGNOR-272619

P67870

Q92915

1

phosphorylation

up-regulates activity

0.27

Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents.

SIGNOR-275745

P23760

P15056

0

phosphorylation

up-regulates activity

0.308

BRAF activates PAX3 to control muscle precursor cell migration during forelimb muscle development.|We found that BRAF clearly induced phosphorylation of PAX3 at Ser205 in both cell types (XREF_FIG).

SIGNOR-278435

P00519

Q9BX66

1

phosphorylation

up-regulates activity

0.424

We have here identified Tyr360 in CAP as a major phosphorylation site by c-Abl, although Tyr 632 also might contribute since its substitution in combination with the Y360F mutation reduced the phosphorylation of CAP to a very low level. Y360 in CAP is the major phosphorylation site of c-Abl. Since Tyr326 was not a major c-Abl phosphorylation site, we sought to identify a putative other kinase that might be involved in the phosphorylation of Y326 in CAP.

SIGNOR-278153

Q92886

Q13164

0

phosphorylation

up-regulates activity

0.35

Activation of ERK5 potentiates while inhibition of ERK5 attenuates Neurog1 stimulated neurogenesis.|ERK5 directly phosphorylated Neurog1 in vitro and modulated the transcriptional and pro-neural activity of Neurog1 in cortical progenitors.

SIGNOR-278364

P05771

Q5T7P8

1

phosphorylation

up-regulates activity

0.2

We found by site-directed mutagenesis that Thr418 and/or Thr419 in the polybasic region (KKKTTIK) of the C2B domain--a key region for the function of synaptotagmins--are the PKC target that regulates its inhibitory effect on acrosomal exocytosis. Similarly, we showed that Thr284 in the polybasic region of C2A (KCKLQTR) is the target for PKC-mediated phosphorylation in this domain.

SIGNOR-273565

Q96BR1

O43524

1

phosphorylation

down-regulates activity

0.435

Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a)|However, SGK and Akt display differences with respect to the efficacy with which they phosphorylate the three regulatory sites on FKHRL1. While both kinases can phosphorylate Thr-32, SGK displays a marked preference for Ser-315 whereas Akt favors Ser-253. These findings suggest that SGK and Akt may coordinately regulate the function of FKHRL1 by phosphorylating this transcription factor at distinct sites. The efficient phosphorylation of these three sites on FKHRL1 by SGK and Akt appears to be critical to the ability of growth factors to suppress FKHRL1-dependent transcription, thereby preventing FKHRL1 from inducing cell cycle arrest and apoptosis.

SIGNOR-249135

Q9UQM7

Q86UR5

1

phosphorylation

up-regulates

0.347

Two serine residues in rim1 (ser-241 and ser-287) and one serine residue in rim2 (ser-335) were required for 14-3-3 binding. Incubation with ca2+/calmodulin-dependent protein kinase ii greatly stimulated the interaction of recombinant n-terminal rim but not the s241/287a mutant with 14-3-3,

SIGNOR-103890

Q13148

P00519

0

phosphorylation

up-regulates quantity

0.2

The phosphorylation of tyrosine 43 of TDP-43 by c-Abl led to increased TDP-43 levels in the cytoplasm and increased the formation of G3BP1-positive stress granules in SH-SY5Y cells.

SIGNOR-279135

Q9NZV8

P28482

0

phosphorylation

up-regulates activity

0.367

We determined that the Kv4.2 C-terminal cytoplasmic domain is an effective ERK2 substrate, and that it is phosphorylated at three sites: Thr(602), Thr(607), and Ser(616). Phosphorylation of the Kv4.2 channel by ERK during LTP induction may lead to increased excitability and membrane depolarization of neurons, which would increase the magnitude of the calcium influx and the probability of triggering LTP.

SIGNOR-262935

P06744

O15297

0

dephosphorylation

down-regulates activity

0.24

The WIP1 mediated inhibition of NLK activity markedly decreased the phosphorylation of lymphoid enhancer binding factor 1 (LEF1), enhancing its interaction with beta-catenin.|Wip1 directly dephosphorylates NLK and increases Wnt activity during germ cell development.

SIGNOR-277155

Q9Y4P1

P60520

1

cleavage

up-regulates activity

0.844

In mammals, at least three atg8 homologs, lc3, gabarap, and gate-16, have been identified (fig. 1a), all of which have structural ubiquitin folds (1416). In vivo and in vitro biochemical analyses have shown that human atg4b is an authentic cysteine protease essential for cleavage of the c terminus of each atg8 homolog to expose the c-terminal gly

SIGNOR-141932

P18545

P25098

0

phosphorylation

up-regulates activity

0.2

Mutation of Thr-62 (to Ala) in PDEgamma produced a GRK2 phosphorylation-resistant mutant that was less effective in associating with GRK2 in response to epidermal growth factor and did not potentiate the stimulation of p42/p44 mitogen-activated protein kinase by this growth factor.

SIGNOR-247823

P28482

O00141

0

phosphorylation

up-regulates activity

0.309

SGK1 was found to physically interact with ERK1/2 as well as MEK1/2. Furthermore, SGK1 mediated the phosphorylation of ERK2 on Ser(29) in a serum-dependent manner. Replacement of Ser(29) to aspartic acid, which mimics the phosphorylation of Ser(29), enhanced the ERK2 activity as well as the MEK/ERK complexes formation.

SIGNOR-276223

P27707

P48730

0

phosphorylation

up-regulates activity

0.339

Site-directed mutagenesis demonstrated that only Ser-74 phosphorylation was involved in Deoxycytidine kinase activation by CKI delta, strengthening the key role of this residue in the control of Deoxycytidine kinase activity.|We showed that recombinant CKI delta phosphorylated several residues of bacterially overexpressed Deoxycytidine kinase: Ser-74, but also Ser-11, Ser-15, and Thr-72.

SIGNOR-280233

O14529

Q8TE12

0

transcriptional regulation

up-regulates quantity by expression

0.285

Lmx1a drives Cux2 expression in the cortical hem through activation of a conserved intronic enhancer. Lmx1a knockdown abolishes activation of the Cux2 enhancer in the cortical hem

SIGNOR-263961

Q8WU20

P11362

0

phosphorylation

up-regulates activity

0.867

As shown in xref , wild type FGFR1c phosphorylated FRS2\u03b1 on tyrosine 196 whereas the V429E mutant did not.

SIGNOR-280013

P55265

P31751

0

phosphorylation

down-regulates activity

0.2

AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively

SIGNOR-276192

P08908

O75398

0

transcriptional regulation

down-regulates quantity by repression

0.437

The human 5-HT1A gene (HTR1A) rs6295 risk allele prevents Deaf1 binding to HTR1A, resulting in increased 5-HT1A autoreceptor transcription

SIGNOR-269064

P45983

P42224

1

phosphorylation

up-regulates activity

0.445

SP600125 prevented phosphorylation of STAT1 at Tyr701 site [..] Western blot analysis confirmed that blocking p-JNK using SP600125 markedly reduced STAT3 localization in the nucleus and STAT1 phosphorylation

SIGNOR-251101

Q00535

Q96PV0

1

phosphorylation

up-regulates activity

0.383

CDK5 increases recombinant SYNGAP1 activity on Ras-GAP by 98% and its Rap-GAP activity by 20%.|Interestingly, phosphorylation of SYNGAP1 by CDK5 and CaMKII increases overall SYNGAP1 activity, but also alters the ratio of its GAP activity towards Ras- and Rap-GTPases.

SIGNOR-279157

Q13158

Q9H422

0

phosphorylation

down-regulates activity

0.436

FIST/HIPK3 causes FADD phosphorylation, thereby promoting FIST/HIPK3-FADD-Fas interaction.¬† Phosphorylation occurs on Ser194 close to the COOH terminus of human FADD| Fas ligand-induced activation of Jun NH(2)-terminal kinase is impaired by overexpressed active FIST/HIPK3

SIGNOR-251272

Q13535

P16220

1

phosphorylation

down-regulates

0.347

Atm phosphorylated creb in vitro and in vivo in response to ionizing radiation (ir) and h(2)o(2) on a stress-inducible domain. Ir-induced phosphorylation of creb correlated with a decrease in creb transactivation potential and reduced interaction between creb and its transcriptional coactivator, creb-binding protein (cbp). A creb mutant containing ala substitutions at atm phosphorylation sites displayed enhanced transactivation potentialit is, therefore, likely that atm and atr regulate creb phosphorylation collectively in response to stress stimuli.

SIGNOR-124060

P53350

P12830

1

phosphorylation

down-regulates quantity by destabilization

0.297

Priming phosphorylation of Cdh1 by the Cdk2/cyclin A kinase complex allows Plk1 to bind to Cdh1 and phosphorylate Cdh1 at Ser138 and Ser146. Phosphorylation of Cdh1 at Ser138 and Ser146 then triggers its interaction with, and subsequent ubiquitination by, SCFbeta-TRCP

SIGNOR-274054

Q9UJU2

P19883

1

transcriptional regulation

up-regulates quantity by expression

0.28

We further demonstrate that Fst is a direct target of the WNT/β-catenin pathway. Activation and inactivation of β-catenin induced and inhibited Fst expression, respectively, in both C2C12 cells and mouse embryos. Specific TCF/LEF1 binding sites within the promoter and intron 1 region of the Fst gene were required for RSPO2 and WNT/β-catenin-induced Fst expression.

SIGNOR-251722

P01019

Q9BYF1

0

cleavage

up-regulates activity

0.759

The ACE2 hydrolytic activity is dependent on the C terminus sequence of the substrate, which is evident from the data with the angiotensin peptides. After 2 h, ACE2 hydrolyzes Ang I partially and Ang II completely, although there is no hydrolysis of angiotensin 1–9, angiotensin 1–7, and angiotensin 1–5, which possess the same N terminus.

SIGNOR-256315

Q13535

P54132

1

phosphorylation

up-regulates activity

0.852

It is noteworthy that an active BLM seems to be unnecessary to the activation of BRCA1, either after gamma-rays or HU, even though BRCA1 and BLM helicase are activated by ATR in response to stalled replication, and despite the fact that they colocalize after replication arrest.|These results show that BLM phosphorylation by ATR after replication fork arrest is not important for its relocalization.

SIGNOR-278978

O14920

Q99558

0

phosphorylation

up-regulates

0.714

Activation of the transcription factor nf-kappab by inflammatory cytokines involves the successive action of nf-kappab-inducing kinase (nik) and two ikappab kinases, ikk-alpha and ikk-beta. Here we show that nik preferentially phosphorylates ikk-alpha over ikk-beta

SIGNOR-55949

Q13291

P06241

0

phosphorylation

up-regulates activity

0.658

All 3 tyrosines of CD150 (Tyr281, Tyr307, Tyr327) are phosphorylated by the src kinase Fyn. CD150 is unique among its homologues in the immunoglobulin superfamily in that it is able to bind SAP, a floating SH2 domain, in the absence of tyrosine phosphorylation. In this study, using a detailed mutagenesis mapping approach we have shown that SAP binding to CD150 is in fact bimodal. Prior to tyrosine phosphorylation, SAP binds the membrane-proximal motif surrounding Tyr281. Following tyrosine phosphorylation by tyrosine kinases such as Fyn, SAP binds additionally to the distal motif surrounding Tyr327.

SIGNOR-251182

Q15418

P27361

0

phosphorylation

up-regulates activity

0.718

Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity.Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3.

SIGNOR-102648

Q9P2P5

Q8IY63

1

ubiquitination

up-regulates activity

0.419

These results clearly indicate that HECW2 ubiquitinates AMOTL1 with K63-linked polyubiquitin chains.|Unlike NEDD4.2, HECW2 targeted AMOTL1 and promoted its stability.

SIGNOR-278811

Q9GZU1

P17612

0

phosphorylation

down-regulates

0.2

The stimulatory effect of h89 on mcoln1 function was not observed when ser(557) and ser(559) were mutated to alanine residues, indicating that these two residues are essential for pka-mediated negative regulation of mcoln1.

SIGNOR-158946

P08235

P34947

0

phosphorylation

down-regulates

0.26

We report that GRK5 phosphorylates and inhibits the cardiac MR whereas GRK2 phosphorylates and desensitizes GPER.

SIGNOR-278478

O75688

Q13627

1

dephosphorylation

down-regulates activity

0.236

In conclusion, our study demonstrates that DYRK1A autophosphorylates Ser258, the dephosphorylation target of PPM1B, and PPM1B negatively regulates DYRK1A activity.|We found that PPM1B dephosphorylates DYRK1A at Ser258, contributing to the inhibition of DYRK1A activity.

SIGNOR-277108

Q15418

Q15653

1

phosphorylation

down-regulates quantity by destabilization

0.369

By using recombinant wild-type and mutant IkappaBbeta proteins, both active ERK2 and RSK1 were found to directly phosphorylate IkappaBbeta, but only active RSK1 phosphorylated IkappaBbeta on Ser19 and Ser23, two sites known to mediate the subsequent ubiquitination and degradation.

SIGNOR-280114

P61586

O14827

0

guanine nucleotide exchange factor

up-regulates activity

0.553

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260573

P63000

P10911

0

guanine nucleotide exchange factor

up-regulates activity

0.665

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260557

P20963

Q9Y2R2

0

dephosphorylation

down-regulates activity

0.447

In vitro experiments with purified recombinant proteins demonstrated that PTPN22-D195A/C227S interacted directly with activated Lck, Zap70, and TCRzeta, confirming the initial substrate trap results. Native PTPN22 dephosphorylated Lck and Zap70 at their activating tyrosine residues Tyr-394 and Tyr-493, respectively, but not at the regulatory tyrosines Tyr-505 (Lck) or Tyr-319 (Zap70). Native PTPN22 also dephosphorylated TCRzeta in vitro and in cells, and its substrate trap variant co-immunoprecipitated with TCRzeta when both were coexpressed in 293T cells, establishing TCRzeta as a direct substrate of PTPN22.

SIGNOR-248837

P55157

P04114

1

lipidation

up-regulates activity

0.793

As ApoB is translated, it is lipidated by microsomal triglyceride transfer protein (MTP). MTP adds triglycerides to the nascent ApoB during its co-translational translocation into the lumen of the endoplasmic reticulum.

SIGNOR-252118

Q13541

P42345

0

phosphorylation

down-regulates activity

0.926

Specifically as part of mTORC1, mTOR directly phosphorylates the ribo- somal protein S6 kinases (S6K1 and S6K2) and the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BP1 and 4E-BP2), both of which control specific steps in the initiation of cap-dependent translation

SIGNOR-167184

Q15797

Q13315

0

phosphorylation

up-regulates

0.2

On genotoxic stress, atm phosphorylates bmps-activated smad1 in the nucleus on s239, which disrupts smad1 interaction with protein phosphatase ppm1a, leading to enhanced activation and upregulation of smad1.

SIGNOR-197533

Q9H4B4

O15350

1

phosphorylation

down-regulates activity

0.41

In this study, we found that Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation.|Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation.

SIGNOR-279647

P42772

Q92560

0

transcriptional regulation

up-regulates quantity by expression

0.2

Since we found that ASXL1 and BAP1 both are enriched at the INK4B locus, our results suggest that activation of the INK4B locus requires ASXL1/BAP1-mediated deubiquitinylation of H2AK119ub1.

SIGNOR-241656

P49841

P31749

0

phosphorylation

down-regulates activity

0.792

Active AKT, a common mediator of cell survival signals induced by radiation through multiple intracellular signaling pathways,11, 12 suppresses apoptosis. AKT positively regulates cyclin D1 expression through inactivation of glycogen synthase kinase 3beta (GSK3B). The AKT-mediated phosphorylation of glycogen synthase kinase 3b on serine9 decreases its kinase activity for Thr286 of cyclin D1, which inhibits the nuclear export and the cytoplasmic proteasomal degradation of cyclin D1

SIGNOR-245416

P12931

P03372

1

phosphorylation

up-regulates

0.778

Although the molecular mechanisms underlying ligand-independent activation of era are not completely understood, phosphorylation of a serine residue in af1 has been implicated in the response to epidermal growth factor. Era is also a target for tyrosine phosphorylation, anda single tyrosine residue located immediately adjacent to af2 has been identified as a substrate for src-family tyrosine kinases.

SIGNOR-55857

Q92934

P45983

0

phosphorylation

down-regulates

0.686

Jnk phosphorylates bad at threonine 201, thereby inhibiting bad association with the antiapoptotic molecule bcl-x(l)

SIGNOR-121940

Q13043

Q15208

1

phosphorylation

up-regulates activity

0.332

Although MST1, MST2, and MST3 potently activated NDR1 in vitro, MST4 had only a minor effect.|Indeed, NDR1 phosphorylated at Thr444 by MST1 displayed greatly (7-fold) enhanced protein kinase activity.

SIGNOR-279641

P68400

Q9H257

1

phosphorylation

down-regulates activity

0.346

PVHL Acts as an Adaptor to Promote the Inhibitory Phosphorylation of the NF-κB Agonist Card9 by CK2

SIGNOR-257601

P05129

P28329

1

phosphorylation

up-regulates

0.321

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-129320

Q9BW92

Q2TAL8

0

transcriptional regulation

up-regulates quantity by expression

0.2

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

SIGNOR-269407

Q13315

P41236

1

phosphorylation

down-regulates

0.2

Atm phosphorylates i-2 on serine 43, leading to the dissociation of the pp1-i-2 complex and the activation of pp1.

SIGNOR-160648

P04049

Q13131

0

phosphorylation

down-regulates

0.342

Ampk also phosphorylated full-length, kinase-defective raf-1 (k375m) to generate two [32p]phosphopeptides, one co-migrating with synthetic tryptic peptide containing phospho-ser621 and the other with phospho-ser259. The catalytic subunit of PKA also phosphorylated Ser621 in vitro, while its overexpression in intact cells resulted in increased phosphorylation of Ser621 and decreased activity of Raf-1. These results suggest that phosphorylation of Ser621 inactivates Raf-1, but do not prove that PKA is responsible for this in vivo.

SIGNOR-47148

P48431

Q9UGL1

0

transcriptional regulation

down-regulates quantity by repression

0.309

Phosphorylation of KDM5B at Ser1456 attenuated the occupancy of KDM5B on the promoters of pluripotency genes.

SIGNOR-273450

P35236

P24723

0

phosphorylation

up-regulates activity

0.2

HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.

SIGNOR-276049

Q96GD4

Q8NEM2

1

phosphorylation

up-regulates activity

0.372

AurB phosphorylates Ser634 of SHCBP1 during mitosis. We generated a phosphorylation site mutant, S634A-SHCBP1, which was prematurely recruited to the central spindle during anaphase and inhibited furrowing.

SIGNOR-273552

P06213

P0DP24

1

phosphorylation

down-regulates

0.352

The in vitro phosphorylation of calmodulin by the insulin receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.

SIGNOR-266320

P08588

Q9HD26

0

relocalization

down-regulates

0.342

Overexpression of cal reduces surface expression of beta1ar. Interaction with cal promotes retention of beta1ar within the cell

SIGNOR-128791

Q9UNE7

P56545

1

ubiquitination

down-regulates quantity by destabilization

0.331

Our data showed that CHIP depletion resulted in up-regulation of the steady-state level of CtBP2 ( Fig. 1 B) and that CHIP ubiquitinated CtBP2 for proteasomal degradation ( Fig. 3 A).

SIGNOR-278722

P24941

Q86WB0

1

phosphorylation

down-regulates

0.2

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

SIGNOR-154051

Q13315

Q02880

1

phosphorylation

down-regulates quantity by destabilization

0.411

Specifically, DNA damage signal, triggered by teniposide (VM-26) treatment, activates ATM, cooperating with CK1 to phosphorylate TOP2β on Ser1134 and Ser1130, respectively, in a canonical degron motif to facilitate β-TrCP binding and subsequent degradation.ATM binds with and phosphorylates TOP2β at Ser1134 to promote its degradation by VM-26.

SIGNOR-277510

Q13683

P15172

0

transcriptional regulation

up-regulates quantity by expression

0.286

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

SIGNOR-241518

Q00653

P49841

0

phosphorylation

down-regulates activity

0.271

More recently, phosphorylation of S707 and S711 by GSK3beta has been shown to promote complete proteasomal degradation of p100 involving the E3 ligase Fbw7 .|These studies suggest that a pool of p100 is constitutively phosphorylated by GSK3beta at S707 and S711, triggering the Fbw7 mediated ubiquitination and proteasomal degradation of p100 which controls the levels of p100 available for the non canonical pathway.

SIGNOR-279186

P01903

Q5T0T0

0

polyubiquitination

down-regulates quantity by destabilization

0.2

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

SIGNOR-271411

P18846

Q13362

0

dephosphorylation

up-regulates

0.2

We propose that constitutive hyperphosphorylation by ck1/ck2 maintains atf1 in an inactive state that promotes transcriptional repression. Pp2a/b56c antagonizes phosphorylation of atm sites in both creb and atf5

SIGNOR-167564

P22888

P49116

0

transcriptional regulation

up-regulates quantity by expression

0.2

Functional analysis showed that EAR2 and EAR3/COUP-TFI repressed the hLHR promoter activity, whereas TR4 activated hLHR gene transcription.

SIGNOR-266217

P08034

P17252

0

phosphorylation

up-regulates activity

0.362

Phosphorylation of connexin-32 by protein kinase C prevents its proteolysis by mu-calpain and m-calpain. |In agreement with other authors (see Saez et al., 1990b), we have found that phosphorylation of connexin-32 by protein kinase A and protein kinase C occurs in serine residues, although we have detected trace amounts of phosphothreonine in connexin-32 phosphorylated by protein kinase C (results not shown). Indeed, Se233 has been shown to be the major phosphorylation site catalyzed by protein kinase A. However, Ser233, Ser239, and perhaps other serines are phosphorylated by protein kinase C (Saez et al., 1990b).

SIGNOR-248919

Q9H3D4

Q15149

1

transcriptional regulation

up-regulates quantity by expression

0.2

Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by a marked decrease in expression of several nuclear envelope-associated components (Lamin B1, Lamin A/C, Sun1, Nesprin-3, Plectin) compared with controls. Furthermore, chromatin immunoprecipitation-quantitative PCR assay showed enrichment of p63 on Sun1, Syne3, and Plec promoters, suggesting them as p63 targets.

SIGNOR-263279