GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P06239	P16885	1	phosphorylation	up-regulates	0.558	In vitro phosphorylation experiments with recombinant plcgamma2 and recombinant lck, fyn, and lyn tyrosine kinases showed that phosphorylation of plcgamma2 led to activation of the recombinant enzyme.	SIGNOR-91477
Q99250	P19784	0	phosphorylation	up-regulates activity	0.2	We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. \| inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G.	SIGNOR-275758
P52564	Q9Y6R4	0	phosphorylation	up-regulates activity	0.657	When truncated mapkkk4 (deltamapkkk4) was overexpressed in hek293 cells, it was constitutively activeco-expressed map kinase kinase (mkk)-1, mkk-4, mkk-3 and mkk-6 were activated in vivo by deltamapkkk4. All of the above mkks purified from escherichia coli were phosphorylated and activated by deltamapkkk4 immunoprecipitates in vitro.	SIGNOR-62372
O14763	Q96D59	0	polyubiquitination	down-regulates quantity by destabilization	0.2	RNF183 mediated K63-linked ubiquitination and lysosomal degradation of DR5.	SIGNOR-272212
P24928	Q9NYV4	0	phosphorylation	up-regulates activity	0.784	Cyck/cdk12 can activate transcription and phosphorylate ser2 in the ctd of rnapii / phosphorylation of serine at position 2 (ser2) is thought to be responsible for productive transcriptional elongation and synthesis of full-length mature mrna	SIGNOR-176805
O14965	Q13185	1	phosphorylation	up-regulates activity	0.363	We report for the first time that during mitotic cell division, heterochromatin protein 1\u03b3 colocalizes and is phosphorylated at serine 83 in G2/M phase by Aurora A.	SIGNOR-280185
P51813	Q96T51	1	phosphorylation	up-regulates activity	0.634	Etk interacts with RUFY1 through its SH3 and SH2 domains. RUFY1 is tyrosine-phosphorylated and appears to be a substrate of Etk. Phosphorylation of the two tyrosine residues, Tyr-281 and Tyr-292, located in the linker region of the two coiled-coil domains by Etk seems to be critical for RUFY1 targeting to the endosomes.	SIGNOR-262679
Q99942	Q7Z434	1	ubiquitination	down-regulates quantity by destabilization	0.456	In this study, we showed that the E3 ubiquitin ligase RING-finger protein 5 (RNF5) interacted with VISA at mitochondria in a viral infection-dependent manner. Domain mapping experiments indicated that the C-terminal transmembrane domain of VISA was required for its interaction with RNF5. RNF5 targeted VISA at K362 and K461 for K48-linked ubiquitination and degradation after viral infection, whereas knockdown of RNF5 reversed virus-induced downregulation of VISA at the early phase.	SIGNOR-271489
Q9HCK8	P07197	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-268917
Q15831	Q96L34	1	phosphorylation	up-regulates	0.535	Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold	SIGNOR-122682
P01008	P03951	1	cleavage	down-regulates activity	0.657	Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1	SIGNOR-264137
Q96BR1	P49841	1	phosphorylation	down-regulates activity	0.442	Phosphorylation of GSK3 by PKB or SGK1 inhibits GSK3 activity\|estern blotting using an antibody specific for the PKB/SGK1 consensus phosphorylation site in GSK3a/beta (serine 21 and 9 respectively) revealed an increase in GSK3a/beta phosphorylation in human embryonic kidney 293 (HEK293) cells overexpressing wild type SGK1, constitutively active SGK1, but not catalytically inactive SGK1.\|The effect of SGK1 was mimicked by PKB and SGK3.	SIGNOR-249167
P16403	Q8IYW5	0	polyubiquitination	down-regulates	0.2	ITCH biochemically antagonized RNF168 and RNF8 in polyubiquitination of histone H1.2 ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2. Both RNF168 and RNF8 elicited higher Ubn levels of K46R-H1.2 compared to WT-H1.2, suggesting that Ubn of H1.2 by both E3 ligases occurs at a site apart from K46.	SIGNOR-272927
Q99873	P48729	0	phosphorylation	up-regulates activity	0.2	CSNK1a1 directly bound and phosphorylated PRMT1 to control its genomic targeting to PRMT1-sustained proliferation genes as well as PRMT1-suppressed differentiation genes.\|Taken together, these data support a provisional model in which CSNK1a1 directs PRMT1 to genomic targets that promote self-renewal and suppress terminal differentiation.In the context of transcription regulation, PRMT1 has been generally considered as a transcriptional co-activator.	SIGNOR-279733
Q14703	Q12772	1	cleavage	up-regulates activity	0.594	We present evidence that SKI-1 processes peptides mimicking the cleavage sites of the SKI-1 prosegment, pro-brain-derived neurotrophic factor, and the sterol regulatory element-binding protein SREBP-2	SIGNOR-267496
Q8IWB6	P06493	0	phosphorylation	down-regulates quantity by destabilization	0.333	Cdk1 phosphorylation of Tex14 is required for the Tex14-Plk1 interaction	SIGNOR-273524
Q96K19	Q14571	1	polyubiquitination	down-regulates activity	0.331	In summary, here we present evidence that RNF170 is an E3 ligase that mediates IP3 receptor ubiquitination and processing by the UPP and that it is recruited to activated IP3 receptors by the erlin1/2 complex to which it is constitutively bound.	SIGNOR-271914
P19784	P42768	1	phosphorylation	up-regulates activity	0.347	We identify two phosphorylation sites in the VCA domain of WASP at serines 483 and 484. S483 and S484 are substrates for casein kinase 2 in vitro and in vivo. Phosphorylation of these residues increases the affinity of the VCA domain for the Arp2/3 complex 7-fold and is required for efficient in vitro actin polymerization by the full-length WASP molecule.	SIGNOR-251048
P21802	Q13443	0	cleavage	down-regulates quantity by destabilization	0.257	Truncated FGFR2 was observed in cells transfected with wild-type ADAM9, but not in those with inactive mutant ADAM9 (Figure 5E). In line with this, cells transfected with wild-type ADAM9 showed reduced pErK1/2 in response to FGF2 as compared to controls or cells expressing mutant ADAM9.\|Here we show that MT1-MMP forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9, hence protecting FGFR2 from ADAM9-mediated ectodomain shedding on the cell surface.	SIGNOR-260300
P19447	P68400	0	phosphorylation	down-regulates activity	0.2	Phosphorylation of S751 by CKII inhibits 5′ incision.	SIGNOR-276013
P08575	P41240	0	phosphorylation	up-regulates	0.469	Tyrosine phosphorylation of cd45 phosphotyrosine phosphatase by p50csk kinase creates a binding site for p56lck tyrosine kinase and activates the phosphatase.	SIGNOR-26785
P31947	Q14258	0	ubiquitination	down-regulates quantity by destabilization	0.571	Here we show that Efp is a RING-finger-dependent ubiquitin ligase (E3) that targets proteolysis of 14-3-3 sigma, a negative cell cycle regulator that causes G2 arrest.	SIGNOR-271548
P67775	P05771-2	1	dephosphorylation	down-regulates activity	0.446	Inhibition of PP2A increased phosphorylation at Ser660 that determines calcium sensitivity and activity of PKCbetaII isoform	SIGNOR-248621
Q8TD43	P17252	0	phosphorylation	up-regulates	0.2	Phorbol ester-induced activation of protein kinase c (pkc) increased the ca(2+) sensitivity of wild-type trpm4 but not of two mutants mutated at putative pkc phosphorylation sites.	SIGNOR-132243
Q38SD2	P53350	0	phosphorylation	up-regulates activity	0.345	Here we show that LRRK1 is a PLK1 substrate that is phosphorylated on Ser 1790. PLK1 phosphorylation is required for CDK1-mediated activation of LRRK1 at the centrosomes	SIGNOR-275467
Q9Y297	P47736	1	ubiquitination	down-regulates	0.342	Here, we demonstrated that rap1gap is ubiquitinated and degraded through proteasome pathway in mitosis. Proteolysis of rap1gap requires the plk1 kinase and _-trcp ubiquitin ligase complex.	SIGNOR-203548
P51149	P60484	0	dephosphorylation	up-regulates activity	0.373	PTEN dephosphorylates Rab7 on two conserved residues S72 and Y183, which are necessary for GDP dissociation inhibitor (GDI)-dependent recruitment of Rab7 on to late endosomes and subsequent maturation.	SIGNOR-276960
Q9UQM7	O14713	1	phosphorylation	up-regulates activity	0.307	The point mutation T38D localized within the optimal CaMKII recognition motif of ICAP-1alpha results in a strong defect in cell spreading which cannot be overcome by the inhibition of the endogenous CaMKII. This fact strongly suggests that the phosphorylation of Threonine 38 by CaMKII modulates the alpha5beta1 integrin function. Conversely, the mutation T38A produces an analog of ICAP-1alpha that cannot be phosphorylated and that stimulates cell spreading on fibronectin to a similar extent when CaMKII is inhibited.	SIGNOR-250632
P61586	P17612	0	phosphorylation	down-regulates activity	0.518	PKA phosphorylates RhoA on Ser188. the addition of a negative charge to Ser188 is sufficient to diminish both RhoA activation and activity within the context of a cell.	SIGNOR-250047
Q9BQQ3	P53350	0	phosphorylation	down-regulates quantity	0.729	As GRASP65 is a substrate of cdc2 and polo-like kinase, manipulation of GRASP65 level may affect the localization and activity of these kinases in cell cycle progression, as suggested by a previous study ( ).\|During mitosis, GRASP65 is phosphorylated by two mitotic kinases, cdc2 and polo-like kinase (plk), which leads to GRASP65 deoligomerization and thus Golgi unstacking ( xref , xref ).	SIGNOR-279554
Q13263	Q9Y572	0	phosphorylation	down-regulates activity	0.2	These results indicate that TRIM28 phosphorylation at S473 is RIPK3-dependent and suggest that RIPK1/RIPK3 activation induces TRIM28 phosphorylation at S473, which may play an important role in the regulation of transcriptional activity.	SIGNOR-279107
P49770	P20042	1	guanine nucleotide exchange factor	up-regulates activity	0.751	EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.	SIGNOR-269130
P00519	Q03468	1	phosphorylation	up-regulates activity	0.271	N-terminal region of CSB interacts with the SH3 domain of c-Abl in vitro and in vivo. In addition, c-Abl kinase phosphorylates CSB at Tyr932. our results suggest that c-Abl interacts with and tyrosine phosphorylates CSB. This interaction may play an important role in the response to oxidative stress, resulting in activation of c-Abl, tyrosine phosphorylation of CSB and more efficient BER of oxidative DNA damage. Tyrosine-phosphorylated CSB may serve as a signal for repair proteins to localize to DNA damage and may help maintain active transcription in the nucleolus.	SIGNOR-251933
P53779	P45985	0	phosphorylation	up-regulates	0.744	Two mapkks, sek1 and mkk7, synergistically activate jnk. Sek1 prefers the tyr-185 residue, and mkk7 prefers the thr-183 residue (17, 19).	SIGNOR-137605
Q05655	Q13501	1	phosphorylation	up-regulates activity	0.367	Data presented here suggested that Vps34 stimulates tumor development mainly through PKC-\u03b4- activation of p62.\|In conclusion, elevation of Vps34 results in tumor progression via the PKC-\u03b4-phosphorylation of p62 at S349 and PKC-\u03b4 involved phosphorylation of Raf 1 at Y340/341.\|Vps34 induces PKC-\u03b4-dependent phosphorylation of p62.	SIGNOR-280086
Q9BZE0	Q9UMX1	0	relocalization	down-regulates	0.266	Negative regulation of gli1 and gli2 activator function by suppressor of fused through multiple mechanisms.Together, these observations reveal that su(fu) regulates the activity of gli1 and gli2 through distinct cytoplasmic and nuclear mechanisms.	SIGNOR-142608
P68400	Q06413	1	phosphorylation	up-regulates activity	0.333	We show that serine 59 located between the MADS and MEF2 domains of MEF2C is phosphorylated in vivo and can be phosphorylated in vitro by casein kinase-II (CKII). Phosphorylation of this site enhanced the DNA binding and transcriptional activity of MEF2C by increasing its DNA binding activity 5-fold.	SIGNOR-250914
Q15910	Q8IZL9	0	phosphorylation	up-regulates activity	0.2	In addition to the transcriptional feedback loop, we also identified a feed-forward loop in which CCRK induces EZH2 phosphorylation, thereby promoting p-EZH2 Ser21 -AR physical interaction for CCRK promoter co-occupancy and transcriptional activation.	SIGNOR-279017
Q9UNA0	P16112	1	cleavage	down-regulates quantity by destabilization	0.765	Aggrecan Degradation in Human Cartilage Evidence for both Matrix Metalloproteinase and Aggrecanase Activity in Normal, Osteoarthritic, and Rheumatoid Joints\|Stromelysin-1 (MMP-3), as well as other MMPs, cleave aggrecan in the interglobular domain between Asn341 and Phe342 to generate a G1 fragment with the COOH terminus VDIPEN341 (11–13). This fragment has been isolated and identified by NH2-terminal sequence analysis from human OA cartilage (11). A second proteolytic activity identified as “aggrecanase” also cleaves aggrecan in the interglobular domain, but between Glu373 and Ala374 (19–24), generating a G1 fragment with a COOH terminus of NITEGE374	SIGNOR-266985
P28482	Q8IUX7	1	phosphorylation	up-regulates activity	0.2	We show that DNA binding by AEBP1 requires both the N- and C-terminal domains of AEBP1, and MAPK interaction with AEBP1 (through its N terminus) results in enhanced DNA binding. A threonine at position 623 within the C-terminal domain of AEBP1 plays an important role in DNA binding by AEBP1, because the mutation results in decreased DNA binding by AEBP1, which leads to a decrease in the transcriptional repression ability of AEBP1. We also show that in vitro phosphorylation of AEBP1 by MAPK is greatly reduced upon mutation of T623. These results suggest that MAPK regulates the transcriptional activity of AEBP1 by a novel dual mechanism, in which MAPK interaction enhances and subsequent phosphorylation decreases the DNA-binding ability of AEBP1.	SIGNOR-262897
P00533	Q15759	0	phosphorylation	down-regulates	0.334	P38 map kinase mediates stress-induced internalization of egfrthe underlying mechanism entails phosphorylation of egfr at a short segment (amino acids 1002-1022) containing multiple serines and threonines, as well as phosphorylation of two rab5 effectors, eea1 and gdi.	SIGNOR-149086
P54274	Q9H2K2	0	ADP-ribosylation	down-regulates activity	0.549	Tankyrase 2 poly(ADP-ribosyl)ated itself and TRF1. Overexpression of tankyrase 2 in the nucleus released endogenous TRF1 from telomeres.	SIGNOR-263376
O75533	P24941	0	phosphorylation	up-regulates	0.346	To map the set of phosphorylation sites in sap155-(223-322) that determine its interaction with nipp1, we have identified phosphorylation sites of cyclin e-cdk2 by the sequencing of proteolytically derived phosphopeptide). Three phosphorylation sites were identified as thr244, thr248, and thr313	SIGNOR-90434
Q6SA08	P16220	1	phosphorylation	up-regulates	0.578	Tssk5, a novel member of the testis-specific serine/threonine kinase family, phosphorylates creb at ser-133, and stimulates the cre/creb responsive pathway.	SIGNOR-138289
O15530	Q16512	1	phosphorylation	up-regulates	0.567	It is shown that activation in vitro and in vivo involves the activation loop phosphorylation of prk1/2 by 3-phosphoinositide-dependent protein kinase-1 (pdk1) /pdk1 phosphorylates the prks at their conserved activation loop threonines (thr-774 and thr-816 for prk1 and prk2, respectively)	SIGNOR-76640
Q15139	Q8WUI4	1	phosphorylation	down-regulates	0.478	We show for the first time that vegf stimulated phosphorylation of hdac7 at the sites of ser178, ser344, and ser479we found that phospholipase cgamma/protein kinase c/protein kinase d1 (pkd1)-dependent signal pathway mediated hdac7 phosphorylation and cytoplasmic accumulation by vegf.	SIGNOR-179430
P48730	Q15691	1	phosphorylation	up-regulates activity	0.505	We further show that casein kinase 1\u03b4 binds and phosphorylates EB1 and promotes microtubule growth.	SIGNOR-279165
P37173	P36897	1	phosphorylation	up-regulates activity	0.722	Recent studies have revealed that upon TGF-beta binding several serine and threonine residues in the GS domain of TGF-beta type I receptor (T beta R-I) are phosphorylated by TGF-beta type II receptor (T beta R-II) and that the phosphorylation of GS domain is essential for TGF-beta signalingThese observations indicate that serine 172 and threonine 176 of T beta R-I are dispensable for extracellular matrix protein production but essential to the growth inhibition by TGF-beta	SIGNOR-246728
P02818	P09668	0	cleavage	down-regulates quantity by destabilization	0.283	This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42.	SIGNOR-256325
Q8WUX9	P06493	0	phosphorylation	down-regulates activity	0.2	We found that recombinant CHMP7 could be directly phosphorylated by CDK1/CCNB1 in vitro and that CDK1-phosphorylation reduced the capacity of CHMP7 to sediment (Figure 4A and B).\|We identified direct CDK1 phosphorylation of CHMP7 at Ser3 and Ser441 as a suppressor of both CHMP7\u2019s ability to interact with LEM2 and its ability to assemble, as judged by sedimentation assays.	SIGNOR-279445
Q96L34	P10636	1	phosphorylation	down-regulates activity	0.419	AMPK phosphorylation inhibits tau binding of microtubules. In order to study further the phosphorylation of tau by AMPK, we compared phosphorylation of tau by MARK4 or AMPK using a panel of phospho-tau antibodies (Figure 2A). Five phosphorylation sites common to both kinases were identified (Thr231, Ser262, Ser356, Ser396 and Ser422). In addition, AMPK, but not MARK4, was capable of phosphorylating Ser214 (Figure 2A).	SIGNOR-273935
Q86X55	Q01196	1	methylation	down-regulates activity	0.282	We have found that PRMT4 is highly expressed in HSPCs, where it functions as an inhibitor of myeloid differentiation (Figure 7G). In these cells, PRMT4 methylates RUNX1 at R223, promoting the assembly of a DPF2-containing transcriptional co-repressive complex, and repressing transcription at the miR-223 locus.	SIGNOR-261967
Q99607	Q9UHD2	0	phosphorylation	up-regulates activity	0.361	Taken together, these results suggest that in response to viral infection, ELF4 was phosphorylated by TBK1 and translocated to the nucleus in a MAVS- and STING dependent manner.\|We speculate that overexpressed ELF4 may recruit and be activated by TBK1.	SIGNOR-279130
Q9UM11	P41002	0	ubiquitination	down-regulates quantity by destabilization	0.538	We show that cyclin F, a cell-cycle-regulated substrate receptor (F-box protein) for the SCF, is targeted for degradation by APC/C. Furthermore, we establish that Cdh1 is itself a substrate of SCF(cyclin F). Cyclin F loss impairs Cdh1 degradation and delays S-phase entry, and this delay is reversed by simultaneous removal of Cdh1.	SIGNOR-266363
O96017	Q13535	0	phosphorylation	up-regulates activity	0.86	Atm- and rad3-related also phosphorylates thr68 in addition to thr26 and ser50, which are not phosphorylated to a significant extent by atm in vitro.Substitution of thr68 with ala reduced the extent of phosphorylation and activation of chk2 in response to ir	SIGNOR-81442
P56524	P15976	0	relocalization	up-regulates activity	0.584	GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells.	SIGNOR-275665
P03372	Q13888	0	phosphorylation	up-regulates activity	0.257	TFIIH Phosphorylates Human Estrogen Receptor α at Serine 118 \| We report here that Cdk7 overexpression stimulates transcription activation by ERα by stimulating phosphorylation of S118 in a ligand-dependent manner.	SIGNOR-260817
Q969Q1	P19237	1	polyubiquitination	down-regulates quantity by destabilization	0.36	We used MuRF1 as the E3 as it functions with all these E2s to ubiquitinate one of its typical substrates, troponin I Although UbcH1 and UbcH13/Uev1a support ubiquitination of troponin I by MuRF1, these E2s do not support ubiquitination of S5a, unlike Class I E2s.	SIGNOR-272736
P08237	O60502	0	deglycosylation	up-regulates activity	0.2	Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity\|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively.	SIGNOR-267607
P50750	P35813	0	dephosphorylation	down-regulates activity	0.493	Taken together, our data indicate that PPM1A and to some extent PPM1B are important negative regulators of P-TEFb function	SIGNOR-248490
P49841	Q969R2	1	phosphorylation	up-regulates activity	0.2	CK1a1, JNK1 and CDK1 had the highest site-specific activity for ORP4L, while CDK1, GSK3a, CK1a1 and GSK3b showed the highest specificity for the site when corrected for background activity with ORP4L-S4A. Because of the complexity of the serine/proline-rich site, we did not determine which serine(s) in ORP4L were phosphorylated by candidate kinases.\|We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes.	SIGNOR-264874
O14965	P12755	1	phosphorylation	down-regulates quantity by destabilization	0.2	Here we show that AURKA phosphorylates in vitro the transcripcional co-repressor Ski on aminoacids Ser326 and Ser383. Phosphorylations on these aminoacids decreased Ski protein half-life	SIGNOR-276917
O60729	Q16659	1	dephosphorylation	down-regulates quantity by destabilization	0.571	Reciprocally, we found that the phosphatases Cdc14A and Cdc14B (Cdc is cell-division cycle) bind to ERK3 and reverse its C-terminal phosphorylation in mitosis. Importantly, alanine substitution of the four C-terminal phosphorylation sites markedly decreased the half-life of ERK3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase.\|In vitro phosphorylation of a series of ERK3-deletion mutants by mitotic cell extracts revealed that phosphorylation is confined to the unique C-terminal extension of the protein. Using MS analysis, we identified four novel phosphorylation sites, Ser684, Ser688, Thr698 and Ser705, located at the extreme C-terminus of ERK3.	SIGNOR-248336
Q9HCE7	Q92519	1	ubiquitination	down-regulates quantity by destabilization	0.41	In this study, we found that TRIB2 was up-regulated and exhibited high stability in liver cancer cells compared with other cells. We performed a structure-function analysis of TRIB2 and identified a domain (amino acids 1-5) at the N terminus that interacted with the E3 ubiquitin ligase Smurf1 and was critical for protein stability. Deletion of this domain extended TRIB2 half-life time accompanied with a more significant malignant property compared with wild type TRIB2.	SIGNOR-275432
O14939	Q05655	0	phosphorylation	up-regulates	0.463	Finally, we show that thr566 of pld2 is directly phosphorylated by pkc and that pld2 mutation in this region prevents pld2 activation, pld2 translocation to the edge of lamellipodia, rac translocation, and cell spreading after integrin activation	SIGNOR-167577
Q5T5U3	P61586	1	gtpase-activating protein	down-regulates activity	0.628	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-260475
O60858	P31749	1	polyubiquitination	down-regulates quantity by destabilization	0.353	Here, we demonstrate that overexpression of RFP2 in cells induced apoptosis through proteasomal degradation of MDM2 and AKT. We observed that RFP2 formed a complex with MDM2, a negative regulator of the p53 tumor suppressor, and AKT, a regulator of apoptosis inhibition at the cellular level. Additionally, we found that the interaction of RFP2 with MDM2 and AKT resulted in ubiquitination and proteasomal degradation of MDM2 and AKT in vivo and in vitro.	SIGNOR-271852
Q16549	P18850	1	phosphorylation	up-regulates	0.2	We discovered that azc, an agent that causes the formation of abnormal proteins, stimulates the stress-activated kinase p38 mapk, which phosphorylates atf6	SIGNOR-89813
O14744	P31269	1	methylation	up-regulates activity	0.462	Hoxa9 methylation by prmt5 is essential for endothelial cell expression of leukocyte adhesion molecules. / prmt5 is a critical coactivator component in a newly defined, hoxa9-containing transcription complex./ Hoxa9 is methylated on arg140 by prmt5.	SIGNOR-195526
O95239	P06493	0	phosphorylation	up-regulates activity	0.489	Identification of Cdk phosphorylation of Kif4A at T1161 in early mitosis. We show that Cdk phosphorylation of Kif4A licenses its chromosome localization.	SIGNOR-265994
P01574	Q14653	0	transcriptional regulation	up-regulates quantity by expression	0.665	Similarly, exogenous expression of wild-type Pin1 suppressed TLR3-mediated, IRF3-dependent activation of the IFN-beta promoter and reduced IFN-beta secretion in culture supernatants	SIGNOR-252257
Q96PH1	P28482	0	phosphorylation	up-regulates	0.325	These results suggest that the mek/erk1/2 pathway is necessary but not sufficient to regulate the pma-dependent activation of nox5.	SIGNOR-171847
P27361	P78347	1	phosphorylation	up-regulates	0.374	Tfii-i can be phosphorylated in vitro by erk and mutation of consensus map kinase substrate sites at serines 627 and 633 impairs the phosphorylation of tfii-i by erk and its activity on the c-fos promoter. These results suggest that erk regulates the activity of tfii-i by direct phosphorylation.	SIGNOR-74308
Q14814	P35580	1	transcriptional regulation	up-regulates quantity by expression	0.322	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238766
O15111	O14920	1	phosphorylation	up-regulates activity	0.67	Our data indicate that IKKα stimulates IKKβ kinase activity for the IκBα substrate. Finally, we demonstrate that IKKα can phosphorylate IKKβ in in vitro kinase assays.	SIGNOR-250772
P46531	Q9UBE8	0	phosphorylation	down-regulates	0.382	Nlk-phosphorylated notch1icd is impaired in its ability to form a transcriptionally_ active_ ternary_ complex.	SIGNOR-163697
Q8N531	P29401	1	ubiquitination	up-regulates activity	0.2	Mechanistically, VRK2 promoted Thr287 phosphorylation of TKT and then recruited FBXL6 to promote TKT ubiquitination and activation.	SIGNOR-277843
P98177	P11233	0	phosphorylation	up-regulates activity	0.2	We conclude that Ral-mediated phosphorylation of threonines 447 and 451 is required for proper activity of AFX-WT.	SIGNOR-249665
Q8NER1	Q00535	0	phosphorylation	up-regulates activity	0.2	TNF-alpha overexpression increased Cdk5-mediated phosphorylation of TRPV1 at T407.\|These results suggest that the activation of Cdk5 by p35 enhances the response of TRPV1 to capsaicin, probably by phosphorylation of the channel [34].	SIGNOR-278437
P0C5Y9	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265411
P35372	Q9UQM7	0	phosphorylation	down-regulates	0.2	The decrease in mu-opioid receptor activity after chronic agonist exposure (1 microm [d-ala(2),n-mephe(4),gly-ol(5)]-enkephalin) is largely due to kinase-mediated phosphorylation of intracellular receptor domains. We have recently shown that the substitution of two putative ca(2+)/calmodulin-dependent protein kinase ii (camk ii) phosphorylation sites, s261 and s266, by alanines in the third intracellular loop of the rat mu-opioid receptor (rmor1) confers resistance to camk ii-induced receptor desensitization.	SIGNOR-79682
P05412	Q92630	0	phosphorylation	down-regulates	0.256	Degradation of c-jun/c-myc is a critical process for the g(1)/s transition, which is initiated upon phosphorylation by glycogen synthase kinase 3 ? (gsk3?). However, a specific kinase or kinases responsible for priming phosphorylation events that precede this gsk3? Modification has not been definitively identified. Here, we found that the dual-specificity tyrosine phosphorylation-regulated kinase dyrk2 functions as a priming kinase of c-jun and c-myc.The finding that kinase-active dyrk2 phosphorylated gst_c-jun210_310-wt by detection with an anti_phospho_c-jun(ser243) antibody demonstrated that dyrk2 is a ser243 kinase in vitro	SIGNOR-195771
P06241	Q13224	1	phosphorylation	up-regulates activity	0.768	We have investigated the tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B by exogenous Src Phosphorylation-site specific antibodies identified NR2B Tyr1472 as a phosphorylation site for intrinsic PSD tyrosine kinases	SIGNOR-247176
P17676	P42684	0	phosphorylation	up-regulates	0.274	The y79 amino acid residue of c/ebpbeta was phosphorylated by c-abl or arg. The phosphorylation of c/ebpbeta resulted in an increased c/ebpbeta stability and a potentiation of c/ebpbeta transcription activation activity in cells	SIGNOR-186427
O14874	P53396	1	phosphorylation	up-regulates activity	0.2	BCKDK can activate ACLY and promote the cleavage of citric acid into acetyl-CoA, and oxaloacetate.\|BCKDK can phosphorylate BCKDHA and ATP citrate lyase (ACLY), exerting opposing effects on both.	SIGNOR-280194
O15392	P06493	0	phosphorylation	up-regulates	0.686	Survivin is a member of the inhibitor of apoptosis gene family that has been implicated in both apoptosis inhibition and regulation of mitosisin synchronized cultures, cytosolic survivin abruptly increased at mitosis, physically associated with p34(cdc2), and was phosphorylated by p34(cdc2) on thr(34), in vivo	SIGNOR-115129
Q01844	P05771	0	phosphorylation	down-regulates activity	0.275	Here we report thatews, a nuclearrna-bindingprooncoprotein, contains an iq domain, is phosphorylated byproteinkinase c, and interacts with calmodulin. Interestingly, pkc phosphorylation of ews inhibits its binding to rna homopolymers, and conversely,rna binding to ews interferes with pkc phosphorylation./ these data indicate that ews contains an iq domain with ser266 acting as the primary site for pkc phosphorylation.	SIGNOR-52854
Q99683	P53041	0	dephosphorylation	down-regulates activity	0.597	After exposure of cells to H2O2, ASK1 is transiently activated by autophosphorylation at Thr845. The protein then associates with PP5 (protein serine/threonine phosphatase 5), which inactivates ASK1 by dephosphorylation of Thr845.	SIGNOR-248540
P17612	O60928	1	phosphorylation	up-regulates	0.2	Pka activation induced an increase of kir7.1 currents. This effect was absent in mutant kir7.1 channels lacking pka consensus site (287)s	SIGNOR-181859
P51692	P54764	0	phosphorylation	up-regulates activity	0.375	We have shown here that EphA4 can phosphorylate STAT5B, but it is not yet clear whether the nuclear translocation of phosphorylated STAT5B is enhanced by EphA4.	SIGNOR-278934
O15550	P17947	1	transcriptional regulation	down-regulates quantity by repression	0.252	Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase	SIGNOR-260036
Q13131	Q14524	1	phosphorylation	down-regulates quantity by destabilization	0.2	AMPK was found to phosphorylate Nav1.5 at threonine (T) 101, which then regulates the interaction between Nav1.5 and the autophagic adaptor protein, microtubule-associated protein 1 light chain 3 (LC3), by exposing the LC3-interacting region adjacent to T101 in Nav1.5.	SIGNOR-277432
P23443	Q9HC98	0	phosphorylation	up-regulates activity	0.367	Here we demonstrate that in addition to phosphorylating S6K1 and SGK1 at their hydrophobic motif, NEK6 also phosphorylates S6K1 at two other sites and phosphorylates SGK1 at one other site in vitro. Analysis of the peptides phosphorylated by NEK6 (Fig 2), performed in the present study has confirmed this, and identified two novel sites on S6K1 (Ser53 and Ser403) as major sites of NEK6 phosphorylation.	SIGNOR-262953
P49757	Q8N448	0	polyubiquitination	down-regulates quantity by destabilization	0.605	Polyubiquitination of Human Numb by LNX2. The Zn-RING-Zn domain of LNX2 is a dimer and assumes a rigid elongated structure that undergoes autoubiquitination and undergoes N-terminal polyubiquitination. LNX2 can bind numb and induce its ubiquitination and subsequent proteasomal degradation	SIGNOR-272423
Q00987	Q9NXV6	1	ubiquitination	down-regulates	0.37	Carf interacts with hdm2 and is ubiquitinated and negatively regulated by hdm2 by proteasome-dependent degradation.	SIGNOR-160974
Q8IWL8	P00519	0	phosphorylation	up-regulates activity	0.2	STH interacts with tau and Abl, and Abl phosphorylates STH on its single tyrosine residue.	SIGNOR-279353
Q96J02	P00533	1	polyubiquitination	down-regulates quantity by destabilization	0.48	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-272604
Q9H093	O14974	1	phosphorylation	down-regulates activity	0.466	NUAK2 phosphorylates and inhibits MYPT1, the regulatory subunit of MLC phosphatase, stabilizing actin filaments and mediating contraction of smooth muscle cells ( xref ).	SIGNOR-279081
P51170	P27361	0	phosphorylation	down-regulates quantity by destabilization	0.28	Using a number of different approaches it was demonstrated that the protein kinase acting on betaThr-613 and gammaThr-623 is the extracellular regulated kinase (ERK). It is suggested that an ERK-mediated phosphorylation of betaThr-613 and gammaThr-623 down-regulates the channel by facilitating its interaction with Nedd4.	SIGNOR-249449
P04637	Q92793	0	acetylation	up-regulates activity	0.912	C-terminal acetylation of p53 by p300/CBP and PCAF promotes an open conformation of p53 by preventing the occlusion of the DNA binding domain by the C-terminal tail. This enhances p53 transcriptional activity, leading to growth arrest and/or apoptosis	SIGNOR-261495

P06239

P16885

1

phosphorylation

up-regulates

0.558

In vitro phosphorylation experiments with recombinant plcgamma2 and recombinant lck, fyn, and lyn tyrosine kinases showed that phosphorylation of plcgamma2 led to activation of the recombinant enzyme.

SIGNOR-91477

Q99250

P19784

0

phosphorylation

up-regulates activity

0.2

We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G.

SIGNOR-275758

P52564

Q9Y6R4

0

phosphorylation

up-regulates activity

0.657

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

SIGNOR-62372

O14763

Q96D59

0

polyubiquitination

down-regulates quantity by destabilization

0.2

RNF183 mediated K63-linked ubiquitination and lysosomal degradation of DR5.

SIGNOR-272212

P24928

Q9NYV4

0

phosphorylation

up-regulates activity

0.784

Cyck/cdk12 can activate transcription and phosphorylate ser2 in the ctd of rnapii / phosphorylation of serine at position 2 (ser2) is thought to be responsible for productive transcriptional elongation and synthesis of full-length mature mrna

SIGNOR-176805

O14965

Q13185

1

phosphorylation

up-regulates activity

0.363

We report for the first time that during mitotic cell division, heterochromatin protein 1\u03b3 colocalizes and is phosphorylated at serine 83 in G2/M phase by Aurora A.

SIGNOR-280185

P51813

Q96T51

1

phosphorylation

up-regulates activity

0.634

Etk interacts with RUFY1 through its SH3 and SH2 domains. RUFY1 is tyrosine-phosphorylated and appears to be a substrate of Etk. Phosphorylation of the two tyrosine residues, Tyr-281 and Tyr-292, located in the linker region of the two coiled-coil domains by Etk seems to be critical for RUFY1 targeting to the endosomes.

SIGNOR-262679

Q99942

Q7Z434

1

ubiquitination

down-regulates quantity by destabilization

0.456

In this study, we showed that the E3 ubiquitin ligase RING-finger protein 5 (RNF5) interacted with VISA at mitochondria in a viral infection-dependent manner. Domain mapping experiments indicated that the C-terminal transmembrane domain of VISA was required for its interaction with RNF5. RNF5 targeted VISA at K362 and K461 for K48-linked ubiquitination and degradation after viral infection, whereas knockdown of RNF5 reversed virus-induced downregulation of VISA at the early phase.

SIGNOR-271489

Q9HCK8

P07197

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-268917

Q15831

Q96L34

1

phosphorylation

up-regulates

0.535

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

SIGNOR-122682

P01008

P03951

1

cleavage

down-regulates activity

0.657

Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1

SIGNOR-264137

Q96BR1

P49841

1

phosphorylation

down-regulates activity

0.442

Phosphorylation of GSK3 by PKB or SGK1 inhibits GSK3 activity|estern blotting using an antibody specific for the PKB/SGK1 consensus phosphorylation site in GSK3a/beta (serine 21 and 9 respectively) revealed an increase in GSK3a/beta phosphorylation in human embryonic kidney 293 (HEK293) cells overexpressing wild type SGK1, constitutively active SGK1, but not catalytically inactive SGK1.|The effect of SGK1 was mimicked by PKB and SGK3.

SIGNOR-249167

P16403

Q8IYW5

0

polyubiquitination

down-regulates

0.2

ITCH biochemically antagonized RNF168 and RNF8 in polyubiquitination of histone H1.2 ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2. Both RNF168 and RNF8 elicited higher Ubn levels of K46R-H1.2 compared to WT-H1.2, suggesting that Ubn of H1.2 by both E3 ligases occurs at a site apart from K46.

SIGNOR-272927

Q99873

P48729

0

phosphorylation

up-regulates activity

0.2

CSNK1a1 directly bound and phosphorylated PRMT1 to control its genomic targeting to PRMT1-sustained proliferation genes as well as PRMT1-suppressed differentiation genes.|Taken together, these data support a provisional model in which CSNK1a1 directs PRMT1 to genomic targets that promote self-renewal and suppress terminal differentiation.In the context of transcription regulation, PRMT1 has been generally considered as a transcriptional co-activator.

SIGNOR-279733

Q14703

Q12772

1

cleavage

up-regulates activity

0.594

We present evidence that SKI-1 processes peptides mimicking the cleavage sites of the SKI-1 prosegment, pro-brain-derived neurotrophic factor, and the sterol regulatory element-binding protein SREBP-2

SIGNOR-267496

Q8IWB6

P06493

0

phosphorylation

down-regulates quantity by destabilization

0.333

Cdk1 phosphorylation of Tex14 is required for the Tex14-Plk1 interaction

SIGNOR-273524

Q96K19

Q14571

1

polyubiquitination

down-regulates activity

0.331

In summary, here we present evidence that RNF170 is an E3 ligase that mediates IP3 receptor ubiquitination and processing by the UPP and that it is recruited to activated IP3 receptors by the erlin1/2 complex to which it is constitutively bound.

SIGNOR-271914

P19784

P42768

1

phosphorylation

up-regulates activity

0.347

We identify two phosphorylation sites in the VCA domain of WASP at serines 483 and 484. S483 and S484 are substrates for casein kinase 2 in vitro and in vivo. Phosphorylation of these residues increases the affinity of the VCA domain for the Arp2/3 complex 7-fold and is required for efficient in vitro actin polymerization by the full-length WASP molecule.

SIGNOR-251048

P21802

Q13443

0

cleavage

down-regulates quantity by destabilization

0.257

Truncated FGFR2 was observed in cells transfected with wild-type ADAM9, but not in those with inactive mutant ADAM9 (Figure 5E). In line with this, cells transfected with wild-type ADAM9 showed reduced pErK1/2 in response to FGF2 as compared to controls or cells expressing mutant ADAM9.|Here we show that MT1-MMP forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9, hence protecting FGFR2 from ADAM9-mediated ectodomain shedding on the cell surface.

SIGNOR-260300

P19447

P68400

0

phosphorylation

down-regulates activity

0.2

Phosphorylation of S751 by CKII inhibits 5′ incision.

SIGNOR-276013

P08575

P41240

0

phosphorylation

up-regulates

0.469

Tyrosine phosphorylation of cd45 phosphotyrosine phosphatase by p50csk kinase creates a binding site for p56lck tyrosine kinase and activates the phosphatase.

SIGNOR-26785

P31947

Q14258

0

ubiquitination

down-regulates quantity by destabilization

0.571

Here we show that Efp is a RING-finger-dependent ubiquitin ligase (E3) that targets proteolysis of 14-3-3 sigma, a negative cell cycle regulator that causes G2 arrest.

SIGNOR-271548

P67775

P05771-2

1

dephosphorylation

down-regulates activity

0.446

Inhibition of PP2A increased phosphorylation at Ser660 that determines calcium sensitivity and activity of PKCbetaII isoform

SIGNOR-248621

Q8TD43

P17252

0

phosphorylation

up-regulates

0.2

Phorbol ester-induced activation of protein kinase c (pkc) increased the ca(2+) sensitivity of wild-type trpm4 but not of two mutants mutated at putative pkc phosphorylation sites.

SIGNOR-132243

Q38SD2

P53350

0

phosphorylation

up-regulates activity

0.345

Here we show that LRRK1 is a PLK1 substrate that is phosphorylated on Ser 1790. PLK1 phosphorylation is required for CDK1-mediated activation of LRRK1 at the centrosomes

SIGNOR-275467

Q9Y297

P47736

1

ubiquitination

down-regulates

0.342

Here, we demonstrated that rap1gap is ubiquitinated and degraded through proteasome pathway in mitosis. Proteolysis of rap1gap requires the plk1 kinase and _-trcp ubiquitin ligase complex.

SIGNOR-203548

P51149

P60484

0

dephosphorylation

up-regulates activity

0.373

PTEN dephosphorylates Rab7 on two conserved residues S72 and Y183, which are necessary for GDP dissociation inhibitor (GDI)-dependent recruitment of Rab7 on to late endosomes and subsequent maturation.

SIGNOR-276960

Q9UQM7

O14713

1

phosphorylation

up-regulates activity

0.307

The point mutation T38D localized within the optimal CaMKII recognition motif of ICAP-1alpha results in a strong defect in cell spreading which cannot be overcome by the inhibition of the endogenous CaMKII. This fact strongly suggests that the phosphorylation of Threonine 38 by CaMKII modulates the alpha5beta1 integrin function. Conversely, the mutation T38A produces an analog of ICAP-1alpha that cannot be phosphorylated and that stimulates cell spreading on fibronectin to a similar extent when CaMKII is inhibited.

SIGNOR-250632

P61586

P17612

0

phosphorylation

down-regulates activity

0.518

PKA phosphorylates RhoA on Ser188. the addition of a negative charge to Ser188 is sufficient to diminish both RhoA activation and activity within the context of a cell.

SIGNOR-250047

Q9BQQ3

P53350

0

phosphorylation

down-regulates quantity

0.729

As GRASP65 is a substrate of cdc2 and polo-like kinase, manipulation of GRASP65 level may affect the localization and activity of these kinases in cell cycle progression, as suggested by a previous study ( ).|During mitosis, GRASP65 is phosphorylated by two mitotic kinases, cdc2 and polo-like kinase (plk), which leads to GRASP65 deoligomerization and thus Golgi unstacking ( xref , xref ).

SIGNOR-279554

Q13263

Q9Y572

0

phosphorylation

down-regulates activity

0.2

These results indicate that TRIM28 phosphorylation at S473 is RIPK3-dependent and suggest that RIPK1/RIPK3 activation induces TRIM28 phosphorylation at S473, which may play an important role in the regulation of transcriptional activity.

SIGNOR-279107

P49770

P20042

1

guanine nucleotide exchange factor

up-regulates activity

0.751

EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.

SIGNOR-269130

P00519

Q03468

1

phosphorylation

up-regulates activity

0.271

N-terminal region of CSB interacts with the SH3 domain of c-Abl in vitro and in vivo. In addition, c-Abl kinase phosphorylates CSB at Tyr932. our results suggest that c-Abl interacts with and tyrosine phosphorylates CSB. This interaction may play an important role in the response to oxidative stress, resulting in activation of c-Abl, tyrosine phosphorylation of CSB and more efficient BER of oxidative DNA damage. Tyrosine-phosphorylated CSB may serve as a signal for repair proteins to localize to DNA damage and may help maintain active transcription in the nucleolus.

SIGNOR-251933

P53779

P45985

0

phosphorylation

up-regulates

0.744

Two mapkks, sek1 and mkk7, synergistically activate jnk. Sek1 prefers the tyr-185 residue, and mkk7 prefers the thr-183 residue (17, 19).

SIGNOR-137605

Q05655

Q13501

1

phosphorylation

up-regulates activity

0.367

Data presented here suggested that Vps34 stimulates tumor development mainly through PKC-\u03b4- activation of p62.|In conclusion, elevation of Vps34 results in tumor progression via the PKC-\u03b4-phosphorylation of p62 at S349 and PKC-\u03b4 involved phosphorylation of Raf 1 at Y340/341.|Vps34 induces PKC-\u03b4-dependent phosphorylation of p62.

SIGNOR-280086

Q9BZE0

Q9UMX1

0

relocalization

down-regulates

0.266

Negative regulation of gli1 and gli2 activator function by suppressor of fused through multiple mechanisms.Together, these observations reveal that su(fu) regulates the activity of gli1 and gli2 through distinct cytoplasmic and nuclear mechanisms.

SIGNOR-142608

P68400

Q06413

1

phosphorylation

up-regulates activity

0.333

We show that serine 59 located between the MADS and MEF2 domains of MEF2C is phosphorylated in vivo and can be phosphorylated in vitro by casein kinase-II (CKII). Phosphorylation of this site enhanced the DNA binding and transcriptional activity of MEF2C by increasing its DNA binding activity 5-fold.

SIGNOR-250914

Q15910

Q8IZL9

0

phosphorylation

up-regulates activity

0.2

In addition to the transcriptional feedback loop, we also identified a feed-forward loop in which CCRK induces EZH2 phosphorylation, thereby promoting p-EZH2 Ser21 -AR physical interaction for CCRK promoter co-occupancy and transcriptional activation.

SIGNOR-279017

Q9UNA0

P16112

1

cleavage

down-regulates quantity by destabilization

0.765

Aggrecan Degradation in Human Cartilage Evidence for both Matrix Metalloproteinase and Aggrecanase Activity in Normal, Osteoarthritic, and Rheumatoid Joints|Stromelysin-1 (MMP-3), as well as other MMPs, cleave aggrecan in the interglobular domain between Asn341 and Phe342 to generate a G1 fragment with the COOH terminus VDIPEN341 (11–13). This fragment has been isolated and identified by NH2-terminal sequence analysis from human OA cartilage (11). A second proteolytic activity identified as “aggrecanase” also cleaves aggrecan in the interglobular domain, but between Glu373 and Ala374 (19–24), generating a G1 fragment with a COOH terminus of NITEGE374

SIGNOR-266985

P28482

Q8IUX7

1

phosphorylation

up-regulates activity

0.2

We show that DNA binding by AEBP1 requires both the N- and C-terminal domains of AEBP1, and MAPK interaction with AEBP1 (through its N terminus) results in enhanced DNA binding. A threonine at position 623 within the C-terminal domain of AEBP1 plays an important role in DNA binding by AEBP1, because the mutation results in decreased DNA binding by AEBP1, which leads to a decrease in the transcriptional repression ability of AEBP1. We also show that in vitro phosphorylation of AEBP1 by MAPK is greatly reduced upon mutation of T623. These results suggest that MAPK regulates the transcriptional activity of AEBP1 by a novel dual mechanism, in which MAPK interaction enhances and subsequent phosphorylation decreases the DNA-binding ability of AEBP1.

SIGNOR-262897

P00533

Q15759

0

phosphorylation

down-regulates

0.334

P38 map kinase mediates stress-induced internalization of egfrthe underlying mechanism entails phosphorylation of egfr at a short segment (amino acids 1002-1022) containing multiple serines and threonines, as well as phosphorylation of two rab5 effectors, eea1 and gdi.

SIGNOR-149086

P54274

Q9H2K2

0

ADP-ribosylation

down-regulates activity

0.549

Tankyrase 2 poly(ADP-ribosyl)ated itself and TRF1. Overexpression of tankyrase 2 in the nucleus released endogenous TRF1 from telomeres.

SIGNOR-263376

O75533

P24941

0

phosphorylation

up-regulates

0.346

To map the set of phosphorylation sites in sap155-(223-322) that determine its interaction with nipp1, we have identified phosphorylation sites of cyclin e-cdk2 by the sequencing of proteolytically derived phosphopeptide). Three phosphorylation sites were identified as thr244, thr248, and thr313

SIGNOR-90434

Q6SA08

P16220

1

phosphorylation

up-regulates

0.578

Tssk5, a novel member of the testis-specific serine/threonine kinase family, phosphorylates creb at ser-133, and stimulates the cre/creb responsive pathway.

SIGNOR-138289

O15530

Q16512

1

phosphorylation

up-regulates

0.567

It is shown that activation in vitro and in vivo involves the activation loop phosphorylation of prk1/2 by 3-phosphoinositide-dependent protein kinase-1 (pdk1) /pdk1 phosphorylates the prks at their conserved activation loop threonines (thr-774 and thr-816 for prk1 and prk2, respectively)

SIGNOR-76640

Q15139

Q8WUI4

1

phosphorylation

down-regulates

0.478

We show for the first time that vegf stimulated phosphorylation of hdac7 at the sites of ser178, ser344, and ser479we found that phospholipase cgamma/protein kinase c/protein kinase d1 (pkd1)-dependent signal pathway mediated hdac7 phosphorylation and cytoplasmic accumulation by vegf.

SIGNOR-179430

P48730

Q15691

1

phosphorylation

up-regulates activity

0.505

We further show that casein kinase 1\u03b4 binds and phosphorylates EB1 and promotes microtubule growth.

SIGNOR-279165

P37173

P36897

1

phosphorylation

up-regulates activity

0.722

Recent studies have revealed that upon TGF-beta binding several serine and threonine residues in the GS domain of TGF-beta type I receptor (T beta R-I) are phosphorylated by TGF-beta type II receptor (T beta R-II) and that the phosphorylation of GS domain is essential for TGF-beta signalingThese observations indicate that serine 172 and threonine 176 of T beta R-I are dispensable for extracellular matrix protein production but essential to the growth inhibition by TGF-beta

SIGNOR-246728

P02818

P09668

0

cleavage

down-regulates quantity by destabilization

0.283

This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42.

SIGNOR-256325

Q8WUX9

P06493

0

phosphorylation

down-regulates activity

0.2

We found that recombinant CHMP7 could be directly phosphorylated by CDK1/CCNB1 in vitro and that CDK1-phosphorylation reduced the capacity of CHMP7 to sediment (Figure 4A and B).|We identified direct CDK1 phosphorylation of CHMP7 at Ser3 and Ser441 as a suppressor of both CHMP7\u2019s ability to interact with LEM2 and its ability to assemble, as judged by sedimentation assays.

SIGNOR-279445

Q96L34

P10636

1

phosphorylation

down-regulates activity

0.419

AMPK phosphorylation inhibits tau binding of microtubules. In order to study further the phosphorylation of tau by AMPK, we compared phosphorylation of tau by MARK4 or AMPK using a panel of phospho-tau antibodies (Figure 2A). Five phosphorylation sites common to both kinases were identified (Thr231, Ser262, Ser356, Ser396 and Ser422). In addition, AMPK, but not MARK4, was capable of phosphorylating Ser214 (Figure 2A).

SIGNOR-273935

Q86X55

Q01196

1

methylation

down-regulates activity

0.282

We have found that PRMT4 is highly expressed in HSPCs, where it functions as an inhibitor of myeloid differentiation (Figure 7G). In these cells, PRMT4 methylates RUNX1 at R223, promoting the assembly of a DPF2-containing transcriptional co-repressive complex, and repressing transcription at the miR-223 locus.

SIGNOR-261967

Q99607

Q9UHD2

0

phosphorylation

up-regulates activity

0.361

Taken together, these results suggest that in response to viral infection, ELF4 was phosphorylated by TBK1 and translocated to the nucleus in a MAVS- and STING dependent manner.|We speculate that overexpressed ELF4 may recruit and be activated by TBK1.

SIGNOR-279130

Q9UM11

P41002

0

ubiquitination

down-regulates quantity by destabilization

0.538

We show that cyclin F, a cell-cycle-regulated substrate receptor (F-box protein) for the SCF, is targeted for degradation by APC/C. Furthermore, we establish that Cdh1 is itself a substrate of SCF(cyclin F). Cyclin F loss impairs Cdh1 degradation and delays S-phase entry, and this delay is reversed by simultaneous removal of Cdh1.

SIGNOR-266363

O96017

Q13535

0

phosphorylation

up-regulates activity

0.86

Atm- and rad3-related also phosphorylates thr68 in addition to thr26 and ser50, which are not phosphorylated to a significant extent by atm in vitro.Substitution of thr68 with ala reduced the extent of phosphorylation and activation of chk2 in response to ir

SIGNOR-81442

P56524

P15976

0

relocalization

up-regulates activity

0.584

GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells.

SIGNOR-275665

P03372

Q13888

0

phosphorylation

up-regulates activity

0.257

TFIIH Phosphorylates Human Estrogen Receptor α at Serine 118 | We report here that Cdk7 overexpression stimulates transcription activation by ERα by stimulating phosphorylation of S118 in a ligand-dependent manner.

SIGNOR-260817

Q969Q1

P19237

1

polyubiquitination

down-regulates quantity by destabilization

0.36

We used MuRF1 as the E3 as it functions with all these E2s to ubiquitinate one of its typical substrates, troponin I Although UbcH1 and UbcH13/Uev1a support ubiquitination of troponin I by MuRF1, these E2s do not support ubiquitination of S5a, unlike Class I E2s.

SIGNOR-272736

P08237

O60502

0

deglycosylation

up-regulates activity

0.2

Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively.

SIGNOR-267607

P50750

P35813

0

dephosphorylation

down-regulates activity

0.493

Taken together, our data indicate that PPM1A and to some extent PPM1B are important negative regulators of P-TEFb function

SIGNOR-248490

P49841

Q969R2

1

phosphorylation

up-regulates activity

0.2

CK1a1, JNK1 and CDK1 had the highest site-specific activity for ORP4L, while CDK1, GSK3a, CK1a1 and GSK3b showed the highest specificity for the site when corrected for background activity with ORP4L-S4A. Because of the complexity of the serine/proline-rich site, we did not determine which serine(s) in ORP4L were phosphorylated by candidate kinases.|We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes.

SIGNOR-264874

O14965

P12755

1

phosphorylation

down-regulates quantity by destabilization

0.2

Here we show that AURKA phosphorylates in vitro the transcripcional co-repressor Ski on aminoacids Ser326 and Ser383. Phosphorylations on these aminoacids decreased Ski protein half-life

SIGNOR-276917

O60729

Q16659

1

dephosphorylation

down-regulates quantity by destabilization

0.571

Reciprocally, we found that the phosphatases Cdc14A and Cdc14B (Cdc is cell-division cycle) bind to ERK3 and reverse its C-terminal phosphorylation in mitosis. Importantly, alanine substitution of the four C-terminal phosphorylation sites markedly decreased the half-life of ERK3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase.|In vitro phosphorylation of a series of ERK3-deletion mutants by mitotic cell extracts revealed that phosphorylation is confined to the unique C-terminal extension of the protein. Using MS analysis, we identified four novel phosphorylation sites, Ser684, Ser688, Thr698 and Ser705, located at the extreme C-terminus of ERK3.

SIGNOR-248336

Q9HCE7

Q92519

1

ubiquitination

down-regulates quantity by destabilization

0.41

In this study, we found that TRIB2 was up-regulated and exhibited high stability in liver cancer cells compared with other cells. We performed a structure-function analysis of TRIB2 and identified a domain (amino acids 1-5) at the N terminus that interacted with the E3 ubiquitin ligase Smurf1 and was critical for protein stability. Deletion of this domain extended TRIB2 half-life time accompanied with a more significant malignant property compared with wild type TRIB2.

SIGNOR-275432

O14939

Q05655

0

phosphorylation

up-regulates

0.463

Finally, we show that thr566 of pld2 is directly phosphorylated by pkc and that pld2 mutation in this region prevents pld2 activation, pld2 translocation to the edge of lamellipodia, rac translocation, and cell spreading after integrin activation

SIGNOR-167577

Q5T5U3

P61586

1

gtpase-activating protein

down-regulates activity

0.628

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-260475

O60858

P31749

1

polyubiquitination

down-regulates quantity by destabilization

0.353

Here, we demonstrate that overexpression of RFP2 in cells induced apoptosis through proteasomal degradation of MDM2 and AKT. We observed that RFP2 formed a complex with MDM2, a negative regulator of the p53 tumor suppressor, and AKT, a regulator of apoptosis inhibition at the cellular level. Additionally, we found that the interaction of RFP2 with MDM2 and AKT resulted in ubiquitination and proteasomal degradation of MDM2 and AKT in vivo and in vitro.

SIGNOR-271852

Q16549

P18850

1

phosphorylation

up-regulates

0.2

We discovered that azc, an agent that causes the formation of abnormal proteins, stimulates the stress-activated kinase p38 mapk, which phosphorylates atf6

SIGNOR-89813

O14744

P31269

1

methylation

up-regulates activity

0.462

Hoxa9 methylation by prmt5 is essential for endothelial cell expression of leukocyte adhesion molecules. / prmt5 is a critical coactivator component in a newly defined, hoxa9-containing transcription complex./ Hoxa9 is methylated on arg140 by prmt5.

SIGNOR-195526

O95239

P06493

0

phosphorylation

up-regulates activity

0.489

Identification of Cdk phosphorylation of Kif4A at T1161 in early mitosis. We show that Cdk phosphorylation of Kif4A licenses its chromosome localization.

SIGNOR-265994

P01574

Q14653

0

transcriptional regulation

up-regulates quantity by expression

0.665

Similarly, exogenous expression of wild-type Pin1 suppressed TLR3-mediated, IRF3-dependent activation of the IFN-beta promoter and reduced IFN-beta secretion in culture supernatants

SIGNOR-252257

Q96PH1

P28482

0

phosphorylation

up-regulates

0.325

These results suggest that the mek/erk1/2 pathway is necessary but not sufficient to regulate the pma-dependent activation of nox5.

SIGNOR-171847

P27361

P78347

1

phosphorylation

up-regulates

0.374

Tfii-i can be phosphorylated in vitro by erk and mutation of consensus map kinase substrate sites at serines 627 and 633 impairs the phosphorylation of tfii-i by erk and its activity on the c-fos promoter. These results suggest that erk regulates the activity of tfii-i by direct phosphorylation.

SIGNOR-74308

Q14814

P35580

1

transcriptional regulation

up-regulates quantity by expression

0.322

Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation

SIGNOR-238766

O15111

O14920

1

phosphorylation

up-regulates activity

0.67

Our data indicate that IKKα stimulates IKKβ kinase activity for the IκBα substrate. Finally, we demonstrate that IKKα can phosphorylate IKKβ in in vitro kinase assays.

SIGNOR-250772

P46531

Q9UBE8

0

phosphorylation

down-regulates

0.382

Nlk-phosphorylated notch1icd is impaired in its ability to form a transcriptionally_ active_ ternary_ complex.

SIGNOR-163697

Q8N531

P29401

1

ubiquitination

up-regulates activity

0.2

Mechanistically, VRK2 promoted Thr287 phosphorylation of TKT and then recruited FBXL6 to promote TKT ubiquitination and activation.

SIGNOR-277843

P98177

P11233

0

phosphorylation

up-regulates activity

0.2

We conclude that Ral-mediated phosphorylation of threonines 447 and 451 is required for proper activity of AFX-WT.

SIGNOR-249665

Q8NER1

Q00535

0

phosphorylation

up-regulates activity

0.2

TNF-alpha overexpression increased Cdk5-mediated phosphorylation of TRPV1 at T407.|These results suggest that the activation of Cdk5 by p35 enhances the response of TRPV1 to capsaicin, probably by phosphorylation of the channel [34].

SIGNOR-278437

P0C5Y9

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265411

P35372

Q9UQM7

0

phosphorylation

down-regulates

0.2

The decrease in mu-opioid receptor activity after chronic agonist exposure (1 microm [d-ala(2),n-mephe(4),gly-ol(5)]-enkephalin) is largely due to kinase-mediated phosphorylation of intracellular receptor domains. We have recently shown that the substitution of two putative ca(2+)/calmodulin-dependent protein kinase ii (camk ii) phosphorylation sites, s261 and s266, by alanines in the third intracellular loop of the rat mu-opioid receptor (rmor1) confers resistance to camk ii-induced receptor desensitization.

SIGNOR-79682

P05412

Q92630

0

phosphorylation

down-regulates

0.256

Degradation of c-jun/c-myc is a critical process for the g(1)/s transition, which is initiated upon phosphorylation by glycogen synthase kinase 3 ? (gsk3?). However, a specific kinase or kinases responsible for priming phosphorylation events that precede this gsk3? Modification has not been definitively identified. Here, we found that the dual-specificity tyrosine phosphorylation-regulated kinase dyrk2 functions as a priming kinase of c-jun and c-myc.The finding that kinase-active dyrk2 phosphorylated gst_c-jun210_310-wt by detection with an anti_phospho_c-jun(ser243) antibody demonstrated that dyrk2 is a ser243 kinase in vitro

SIGNOR-195771

P06241

Q13224

1

phosphorylation

up-regulates activity

0.768

We have investigated the tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B by exogenous Src Phosphorylation-site specific antibodies identified NR2B Tyr1472 as a phosphorylation site for intrinsic PSD tyrosine kinases

SIGNOR-247176

P17676

P42684

0

phosphorylation

up-regulates

0.274

The y79 amino acid residue of c/ebpbeta was phosphorylated by c-abl or arg. The phosphorylation of c/ebpbeta resulted in an increased c/ebpbeta stability and a potentiation of c/ebpbeta transcription activation activity in cells

SIGNOR-186427

O14874

P53396

1

phosphorylation

up-regulates activity

0.2

BCKDK can activate ACLY and promote the cleavage of citric acid into acetyl-CoA, and oxaloacetate.|BCKDK can phosphorylate BCKDHA and ATP citrate lyase (ACLY), exerting opposing effects on both.

SIGNOR-280194

O15392

P06493

0

phosphorylation

up-regulates

0.686

Survivin is a member of the inhibitor of apoptosis gene family that has been implicated in both apoptosis inhibition and regulation of mitosisin synchronized cultures, cytosolic survivin abruptly increased at mitosis, physically associated with p34(cdc2), and was phosphorylated by p34(cdc2) on thr(34), in vivo

SIGNOR-115129

Q01844

P05771

0

phosphorylation

down-regulates activity

0.275

Here we report thatews, a nuclearrna-bindingprooncoprotein, contains an iq domain, is phosphorylated byproteinkinase c, and interacts with calmodulin. Interestingly, pkc phosphorylation of ews inhibits its binding to rna homopolymers, and conversely,rna binding to ews interferes with pkc phosphorylation./ these data indicate that ews contains an iq domain with ser266 acting as the primary site for pkc phosphorylation.

SIGNOR-52854

Q99683

P53041

0

dephosphorylation

down-regulates activity

0.597

After exposure of cells to H2O2, ASK1 is transiently activated by autophosphorylation at Thr845. The protein then associates with PP5 (protein serine/threonine phosphatase 5), which inactivates ASK1 by dephosphorylation of Thr845.

SIGNOR-248540

P17612

O60928

1

phosphorylation

up-regulates

0.2

Pka activation induced an increase of kir7.1 currents. This effect was absent in mutant kir7.1 channels lacking pka consensus site (287)s

SIGNOR-181859

P51692

P54764

0

phosphorylation

up-regulates activity

0.375

We have shown here that EphA4 can phosphorylate STAT5B, but it is not yet clear whether the nuclear translocation of phosphorylated STAT5B is enhanced by EphA4.

SIGNOR-278934

O15550

P17947

1

transcriptional regulation

down-regulates quantity by repression

0.252

Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase

SIGNOR-260036

Q13131

Q14524

1

phosphorylation

down-regulates quantity by destabilization

0.2

AMPK was found to phosphorylate Nav1.5 at threonine (T) 101, which then regulates the interaction between Nav1.5 and the autophagic adaptor protein, microtubule-associated protein 1 light chain 3 (LC3), by exposing the LC3-interacting region adjacent to T101 in Nav1.5.

SIGNOR-277432

P23443

Q9HC98

0

phosphorylation

up-regulates activity

0.367

Here we demonstrate that in addition to phosphorylating S6K1 and SGK1 at their hydrophobic motif, NEK6 also phosphorylates S6K1 at two other sites and phosphorylates SGK1 at one other site in vitro. Analysis of the peptides phosphorylated by NEK6 (Fig 2), performed in the present study has confirmed this, and identified two novel sites on S6K1 (Ser53 and Ser403) as major sites of NEK6 phosphorylation.

SIGNOR-262953

P49757

Q8N448

0

polyubiquitination

down-regulates quantity by destabilization

0.605

Polyubiquitination of Human Numb by LNX2. The Zn-RING-Zn domain of LNX2 is a dimer and assumes a rigid elongated structure that undergoes autoubiquitination and undergoes N-terminal polyubiquitination. LNX2 can bind numb and induce its ubiquitination and subsequent proteasomal degradation

SIGNOR-272423

Q00987

Q9NXV6

1

ubiquitination

down-regulates

0.37

Carf interacts with hdm2 and is ubiquitinated and negatively regulated by hdm2 by proteasome-dependent degradation.

SIGNOR-160974

Q8IWL8

P00519

0

phosphorylation

up-regulates activity

0.2

STH interacts with tau and Abl, and Abl phosphorylates STH on its single tyrosine residue.

SIGNOR-279353

Q96J02

P00533

1

polyubiquitination

down-regulates quantity by destabilization

0.48

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-272604

Q9H093

O14974

1

phosphorylation

down-regulates activity

0.466

NUAK2 phosphorylates and inhibits MYPT1, the regulatory subunit of MLC phosphatase, stabilizing actin filaments and mediating contraction of smooth muscle cells ( xref ).

SIGNOR-279081

P51170

P27361

0

phosphorylation

down-regulates quantity by destabilization

0.28

Using a number of different approaches it was demonstrated that the protein kinase acting on betaThr-613 and gammaThr-623 is the extracellular regulated kinase (ERK). It is suggested that an ERK-mediated phosphorylation of betaThr-613 and gammaThr-623 down-regulates the channel by facilitating its interaction with Nedd4.

SIGNOR-249449

P04637

Q92793

0

acetylation

up-regulates activity

0.912

C-terminal acetylation of p53 by p300/CBP and PCAF promotes an open conformation of p53 by preventing the occlusion of the DNA binding domain by the C-terminal tail. This enhances p53 transcriptional activity, leading to growth arrest and/or apoptosis

SIGNOR-261495