GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q9Y618	Q04206	0	relocalization	down-regulates activity	0.404	Furthermore, overexpression of Flt3-ITD led to a partial relocalization of SMRT protein from the nucleus to the cytoplasm. This indicates that shuttling of p65 was necessary for Flt3-ITD-mediated SMRT nuclear export.	SIGNOR-261539
Q86UZ6	P15018	1	transcriptional regulation	up-regulates quantity by expression	0.2	ZBTB46 binds directly to the LIF regulatory sequence and enhances its transcription. Our study confirmed a novel positive association between ZBTB46 activity and LIF levels in prostate cancer tissues and cells. Under androgen regulation, low levels of ZBTB46 are an essential transcriptional factor for maintaining LIF-STAT3 signaling, while the loss of androgen signaling or inhibition of AR signaling causes LIF-enhanced therapeutic resistance and CRPC characteristics through the upregulation of ZBTB46. We also found that LIF activation drives malignant progression and NE-like reprogramming in prostate cancer by activating STAT3 signaling.	SIGNOR-277988
P06493	Q14980	1	phosphorylation	down-regulates	0.587	Cdk1-mediated phosphorylation at t2055 negatively regulates numa cortical localization and that this phosphorylation is counteracted by ppp2ca phosphatase activity.	SIGNOR-194825
Q14258	O43283	0	phosphorylation	up-regulates quantity by stabilization	0.2	Mechanistically, MAP3K13 phosphorylates the E3 ubiquitin ligase TRIM25 at Ser12 to decrease its polyubiquitination and proteasomal degradation.	SIGNOR-277456
Q4V328	P42574	0	cleavage	up-regulates activity	0.414	These results suggest that the region of GRASP‐1 downstream of the Caspase‐3‐cleavage site is capable of activating the JNK signaling pathway by enhancing the phosphorylation of JNK. these results suggest that full length GRASP‐1 does not enhance JNK pathway activity, possibly due to the inhibitory effect of the N‐terminal fragment on the C‐terminal fragment. In contrast, Caspase‐3 cleavage of GRASP‐1 releases the C‐terminal fragment, which in turn activates JNK signaling by serving as a scaffold protein.	SIGNOR-260641
P49593	Q13177	1	dephosphorylation	down-regulates	0.261	Pop x2, a pp 2c serine/threonine phosphatase, is known to dephosphorylate pak and downregulate its activity.	SIGNOR-162149
Q92831	Q5TEC6	1	acetylation	down-regulates activity	0.2	The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.	SIGNOR-269624
P00519	Q9UPY6	1	phosphorylation	up-regulates activity	0.582	WAVE3-Abl interaction promotes the tyrosine phosphorylation of WAVE3 by Abl, and STI-571, a specific inhibitor of Abl kinase activity, abrogates the Abl-mediated phosphorylation of WAVE3.	SIGNOR-259077
Q9UHD2	A7MCY6	0	relocalization	up-regulates activity	0.603	TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation	SIGNOR-272469
Q9NRC8	Q9NR30	1	deacetylation	up-regulates activity	0.26	Significantly, the activity of DDX21 is regulated by acetylation. Acetylation by CBP inhibits DDX21 activity, while deacetylation by SIRT7 augments helicase activity and overcomes R-loop-mediated stalling of RNA polymerases.\|acetylation of K18, K137, and K600 impairs the helicase activity of DDX21.	SIGNOR-275903
Q92974	O14965	0	phosphorylation	down-regulates activity	0.332	The mitotic kinases Aurora A/B and Cdk1/Cyclin B phosphorylate GEF-H1, thereby inhibiting GEF-H1 catalytic activity.	SIGNOR-276061
Q5VWQ8	Q13309	0	ubiquitination	down-regulates quantity by destabilization	0.267	DAB2IP protein levels can be negatively regulated by the activity of the E3-ubiquitin ligases Fbw7, Skp2, and Smurf1	SIGNOR-254775
P31273	O15550	0	transcriptional regulation	up-regulates quantity by expression	0.307	Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.	SIGNOR-260029
P49336	Q16695	1	phosphorylation	down-regulates activity	0.2	However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo.	SIGNOR-273175
Q9UI46	Q92949	0	transcriptional regulation	up-regulates quantity by expression	0.368	FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).	SIGNOR-266932
Q7Z6E9	Q8NAP3	1	ubiquitination	down-regulates quantity by destabilization	0.423	Thus, RBBP6 induces ZBTB38 protein degradation, and this depends on the activity of the proteasome.We next tested whether RBBP6 might directly ubiquitinate ZBTB38.\|We show that ZBTB38 is directly ubiquitinated by RBBP6 in human and mouse cells, in a process that is independent of p53 and MDM2, and leads to proteasomal degradation.	SIGNOR-278594
Q00535	Q05397	1	phosphorylation	up-regulates	0.305	Here, we show that fak phosphorylation by cdk5 at s732 is important for microtubule organization, nuclear movement, and neuronal migration. In cultured neurons, s732-phosphorylated fak is enriched along a centrosome-associated microtubule fork that abuts the nucleus. Overexpression of the nonphosphorylatable mutant fak s732a results in disorganization of the microtubule fork and impairment of nuclear movement in vitro, and neuronal positioning defects in vivo.	SIGNOR-86223
Q13882	P40763	1	phosphorylation	up-regulates activity	0.622	29 PTK6 promotes activating phosphorylation of STAT3 at tyrosine residue 705.\|STAT3 has been shown to promote tumor initiation of different tumor types, including those of the gastrointestinal tract and skin, and PTK6 was previously shown to promote STAT3 activation and tumorigenesis in mouse models of colon and skin cancer.	SIGNOR-278346
O43164	Q9Y4C4	1	ubiquitination	up-regulates activity	0.403	These results suggest that the ubiquitylation of MFHAS1 by praja2 has a vital role in M1 macrophage polarization and promotes the transformation of M2 macrophages to M1 macrophages through both the JNK and p38 pathways.	SIGNOR-278559
P63104	P11309	0	phosphorylation	up-regulates activity	0.31	PIM1 phosphorylates the AR and 14-3-3 ζ and coordinates their interaction. PIM1 phosphorylation of the AR and 14-3-3 ζ enhances their interaction and shifts their occupancy on chromatin, resulting in 14-3-3 ζ co-regulation of AR, likely by recruiting other AR co-regulators such as hnRNPK and TRIM28.	SIGNOR-277574
Q92830	Q6NXT2	1	acetylation	down-regulates activity	0.2	The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.	SIGNOR-269608
O15355	P63162	1	dephosphorylation	up-regulates quantity by stabilization	0.2	Dephosphorylation of survival motor neurons (SMN) by PPM1G and PP2Cgamma governs Cajal body localization and stability of the SMN complex.\|This indicates that the catalytic activity of PPM1G promotes accumulation of the SMN complex in CBs and suggests that PPM1G is a major determinant of the SMN-complex localization in the nucleus.	SIGNOR-277021
P00519	Q14191	1	phosphorylation	up-regulates	0.41	We thus hypothesized that wrn may interact with the abl tyrosine kinase in the dna damage response. Here, we provide evidence for a functional and physical interaction between wrn and c-abl, including wrn relocalization in response to dna damage, suggesting that this protein-protein interaction participates in a shared pathway of genome surveillance.	SIGNOR-86497
Q9UBU7	Q13535	0	phosphorylation	down-regulates	0.657	Dbf4/cdc7 (dbf4-dependent kinase (ddk)) is activated at the onset of s-phase, and its kinase activity is required for dna replication initiation from each origin. We identified novel atm/atr phosphorylation sites on dbf4 and showed that atm/atr-mediated phosphorylation of dbf4 is critical for the intra-s-phase checkpoint to inhibit dna replication.	SIGNOR-177809
Q9Y566	O14490	0	relocalization	up-regulates activity	0.857	SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).	SIGNOR-264586
Q9UBK2	P31751	0	phosphorylation	down-regulates	0.348	Here we describe a mechanism by which insulin, through the intermediary protein kinase akt2/protein kinase b (pkb)-beta, elicits the phosphorylation and inhibition of the transcriptional coactivator peroxisome proliferator-activated receptor-coactivator 1alpha (pgc-1alpha), a global regulator of hepatic metabolism during fasting / phosphorylation of pgc-1? At ser?570 Is required for akt to inhibit recruitment of pgc-1? To chromatin.	SIGNOR-155536
P31749	Q15942	1	phosphorylation	down-regulates	0.415	Akt binds and phosphorylates zyxin on serine 142, leading to its association with acinus zyxin is a substrate of caspases, but akt phosphorylation fails to protect its proteolytic degradation	SIGNOR-156122
P28482	Q15797	1	phosphorylation	down-regulates	0.608	Phosphorylation of the linker region of smads mediated by erk2, gsk3?, And cdk2/4 negatively regulates smad activity by preventing their relocation to the nucleus, by inhibiting their interactions with coactivators, or by accelerating their degradation;in contrast, erk2 phosphorylated all four smad1 residues almost evenly, while showing a preference for s204 over s208 and s213 in smad3	SIGNOR-161597
Q15797	P35813	0	dephosphorylation	down-regulates	0.538	In this study, we have found that ppm1a, a metal ion-dependent protein serine/threonine phosphatase, physically interacts with and dephosphorylates smad1 both in vitro and in vivo. considering the highly conserved nature of the sxs motif in all r-smads, we reasoned that ppm1a might also recognize the sxs motif in the bmp-activated smad1.	SIGNOR-149077
P45984	P35568	1	phosphorylation	down-regulates	0.706	Map kinases and mtor mediate insulin-induced phosphorylation ofinsulinreceptor substrate-1 on serine residues 307, 612 and 632	SIGNOR-118877
P17612	P13796	1	phosphorylation	up-regulates	0.327	Phosphorylation on ser5 increases the f-actin-binding activity of l-plastin and promotes its targeting to sites of actin assembly in cells. L-plastin phosphorylation require protein kinase a.	SIGNOR-146287
P17252	Q96PY5	1	phosphorylation	up-regulates activity	0.2	PKCα associates with and phosphorylates FMNL2 at S1072 within its Diaphanous autoregulatory region, leading to the release of formin autoinhibition.	SIGNOR-273796
P43268	Q15831	0	phosphorylation	down-regulates quantity by destabilization	0.622	LKB1 phosphorylated PEA3 and promoted its degradation through a proteasome-mediated mechanism.	SIGNOR-279293
Q99497	Q8IW41	0	phosphorylation	up-regulates activity	0.469	PRAK preferentially colocalizes with DJ-1 and leads to DJ-1 activation, which in turn facilitates DJ-1 to sequester Daxx in the nucleus, preventing oxidative stress induced cell death.\|These data clearly demonstrate a PRAK dependent phosphorylation of DJ-1.	SIGNOR-279746
P06239	P27986	1	phosphorylation	down-regulates activity	0.623	the regulatory p85 subunit of phosphatidylinositol 3-kinase is phosphorylated on tyrosine residues. We report that this phosphorylation event is readily catalyzed by the Abl and Lck protein-tyrosine kinases in vitro, by Bcr-Abl or a catalytically activated Lck-Y505F in co-transfected COS cells. we have mapped a major phosphorylation site to Tyr-688 in the C-terminal SH2 domain of p85. Tyrosine phosphorylation of p85 in vitro or in vivo was not associated with detectable change in the enzymatic activity of the phosphatidylinositol 3-kinase heterodimer, but correlated with a strong reduction in the binding of some, but not all, phosphoproteins to the SH2 domains of p85.	SIGNOR-251383
O00308	P48431	1	ubiquitination	down-regulates quantity	0.361	Among the four E3 ligases, only WWP2 knockdown was found to increase SOX2 protein levels in GSCs (Fig.\u00a04A).\|We first verified that WWP2 ubiquitinates SOX2 in vitro.	SIGNOR-278798
O00213	P49841	0	phosphorylation	up-regulates quantity	0.293	In this regards, GSK3beta may promote amyloidogenic processing of APP by regulating the cellular level of monomeric FE65 for the formation of LRP1, FE65, and APP complex.\|In this study, we showed that FE65 is phosphorylated at T579 by GSK3beta.	SIGNOR-278359
Q8WU17	O15503	1	ubiquitination	down-regulates quantity	0.477	TRC8/RNF139 encodes an endoplasmic reticulum-resident E3 ubiquitin ligase that inhibits growth in a RING- and ubiquitylation-dependent manner. TRC8 also contains a predicted sterol-sensing domain. Here, we report that TRC8 protein levels are sterol responsive and that it binds and stimulates ubiquitylation of the endoplasmic reticulum anchor protein INSIG. Thus, we conclude that INSIG-1 and 2 physically interact with TRC8, and that TRC8 enhances ubiquitylation of INSIG-1 in a RING-dependent manner	SIGNOR-271955
Q96EP1	P53350	1	polyubiquitination	down-regulates quantity by destabilization	0.468	Chfr, a mitotic stress checkpoint, plays an important role in cell cycle progression, tumor suppression and the processes that require the E3 ubiquitin ligase activity mediated by the RING finger domain. Chfr stimulates the formation of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins including Plk1 and Aurora A.	SIGNOR-271464
P38936	O14757	0	phosphorylation	down-regulates quantity by destabilization	0.531	Responsible for this degradation is the checkpoint kinase Chk1, which phosphorylates p21(Waf1) on T145 and S146 residues and induces its proteasome-dependent proteolysis.	SIGNOR-279325
Q9UBK2	Q13131	0	phosphorylation	up-regulates activity	0.575	Ampk phosphorylates pgc-1alpha directly both in vitro and in cells. These direct phosphorylations of the pgc-1alpha protein at threonine-177 and serine-538.	SIGNOR-156780
P51946	P49336	0	phosphorylation	down-regulates	0.645	Cdk8 phosphorylates mammalian cyclin h in the vicinity of its functionally unique amino-terminal and carboxy-terminal alpha-helical domains. This phosphorylation represses both the ability of tfiih to activate transcription and its ctd kinase activity	SIGNOR-82033
Q9UNI6	Q99683	1	dephosphorylation	down-regulates activity	0.25	Our study showed that DUSP12 inhibited ASK1-JNK activation and DUSP12 can directly bind to and dephosphorylate ASK1.	SIGNOR-277032
P55011	Q9BYP7	0	phosphorylation	up-regulates activity	0.525	We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities\|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs	SIGNOR-264625
O75534	P35637	0	post transcriptional regulation	up-regulates quantity by stabilization	0.2	These findings demonstrated that LINC00205 facilitates malignant phenotypes in LC by recruiting FUS to stabilize CSDE1, suggesting LINC00205 as a potential target for LC therapy.\|Subsequent RIP assay con- firmed such prediction, as CSDE1 mRNA was evidently precipitated by anti-FUS (Figure 3A).	SIGNOR-262110
P27361	Q8IVS8	1	phosphorylation	up-regulates quantity by stabilization	0.2	Mechanistically, glucose deprivation-activated ERK1 phosphorylates GLYCTK2 at serine 220 directly, which prevents STUB1 (ubiquitin E3 ligase) binding, thereby abrogating the ubiquitination and degradation of GLYCTK2. ERK1 phosphorylates GLYCTK2 at S220 to promotes its stability	SIGNOR-280257
P41235	P04150	0	transcriptional regulation	up-regulates quantity by expression	0.37	Electrophoretic mobility shift, chromatin immunoprecipitation (ChIP), and streptavidin DNA binding assays revealed that DEX increased binding of HNF4alpha to the HNF4-RE and that an interaction of GR and HNF4alpha occurred at this site.	SIGNOR-251684
O95155	P10636	1	ubiquitination	down-regulates quantity by destabilization	0.2	Ubiquitination and degradation of Tau by UBE4B and STUB1 in mammalian neuroblastoma cells.	SIGNOR-278682
P06239	P15941	1	phosphorylation	up-regulates activity	0.46	The present results demonstrate that Lck phosphorylation of MUC1 on Y-46 also increases binding of MUC1 and beta-catenin. The results further show that ZAP-70 phosphorylation of MUC1-CD stimulates the interaction of MUC1 and beta-catenin	SIGNOR-249358
Q9UD71	P68400	0	phosphorylation	up-regulates activity	0.34	Study of [Plphosphate release during manual Edman degradation confirmed that the phosphorylated residues in rat DARPP-32 were Ser45 and Ser102. \| Phosphorylation by casein kinase II did not affect the potency of DARPP-32 as an inhibitor of protein phosphatase-1, which depended only on phosphorylation of Thr34 by cAMP-dependent protein kinase. However, phosphorylation of DARPP-32 by casein kinase II facilitated phosphorylation of Thr34 by cAMP-dependent protein kinase	SIGNOR-250927
Q16649	P08700	1	transcriptional regulation	up-regulates quantity by expression	0.527	NF-IL3A transactivates the IL-3 promoter through the A region sequences.	SIGNOR-266222
P43629	Q02156	0	phosphorylation	down-regulates	0.2	Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of ser(394) by protein kinase c slightly suppresses kir3dl1 inhibitory function, and reduces receptor internalization and turnover.	SIGNOR-158129
Q02763	Q03112	0	transcriptional regulation	up-regulates quantity by expression	0.2	We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2	SIGNOR-266063
Q13464	P61587	1	phosphorylation	up-regulates	0.707	We show that rock phosphorylates endogenous rhoe at serine 11 upon cell stimulation with platelet-derived growth factor. Phosphorylation has no effect on rhoe binding to rock i, but instead increases rhoe protein stability.	SIGNOR-134703
P53350	Q8N3U4	1	dephosphorylation	down-regulates activity	0.737	Two phosphorylation sites in Scc1 (Thr144 and Thr312) match the consensus proposed by Nakajima et al. [24]. These two sites, in addition to one in Scc1 (Ser454) and three in SA2 (Thr1109, Ser1137, and Ser1224) conform with the consensus proposed by Barr et al. [25]. These findings are consistent with the possibility that at least some of the sites in Scc1 and SA2 are directly phosphorylated by Plk1.\|Phosphorylation of SA2 Is Essential for the Dissociation of Cohesin from Chromosomes during Prophase and Prometaphase	SIGNOR-275534
Q92793	P04637	1	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
P31270	O15550	0	transcriptional regulation	up-regulates quantity by expression	0.263	Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.	SIGNOR-260021
P30679	Q13794	0	phosphorylation	up-regulates activity	0.2	Ga16 is phosphorylated in vivo by PMA and by TRH receptor stimulation	SIGNOR-278131
P17612	P42858	1	phosphorylation	down-regulates quantity by destabilization	0.2	Moreover, phosphorylation of C-HEAT Ser2550 by cAMP-dependent protein kinase (PKA), the top hit in kinase activity screens, was found to hasten huntingtin degradation, such that levels of the catalytic subunit (PRKACA) were inversely related to huntingtin levels.	SIGNOR-277625
P53779	P14778	0	phosphorylation	up-regulates activity	0.2	Il-1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated mitogen-activated protein (map) kinases, c-jun nh2-terminal kinase (jnk) and p38 map kinase, as well as transcription factor nuclear factor kappab (nf-kappab	SIGNOR-249515
P28562	Q09472	0	acetylation	up-regulates	0.309	A recent report shows that mkp1 may also be regulated by acetylation. When raw macrophages are stimulated with lps, mkp1 becomes acetylated on lys57 by p300	SIGNOR-166581
P28482	P10828	1	phosphorylation	down-regulates activity	0.412	We concluded that serine 142 of the tr dbd is the likely site of phosphorylation by t(4)-activated mapk and that the docking site on tr for activated mapk includes residues 128-133 (kgffrr), a basic amino acid-enriched motif novel for mapk substrates. Tr mutations in the proposed mapk docking domain and at residue 142 modulated t(4)-conditioned shedding of co-repressor and recruitment of co-activator proteins by the receptor, and they altered transcriptional activity of tr in a thyroid hormone response element-luciferase reporter assay.	SIGNOR-102216
Q01196	Q00534	0	phosphorylation	up-regulates	0.615	We have identified four phosphorylation sites on aml1c that are necessary for transcriptional activity of aml1c in k562 and 293t cells (27).4 mutation of these four sites (serine 276, serine 293, serine 303, and threonine 300) to alanine abolishes transcriptional activation, whereas mutation of these sites to aspartic acid (which mimics phosphorylation) results in a hyperactive protein.	SIGNOR-138953
Q15078	P20807	0	cleavage	up-regulates activity	0.261	Calpains also modulate the activity of CDK5. Physiologically, CDK 5 is activated by p35 and its cleaved product p25. The latter has a longer half life than p35 and therefore it is a more potent activator of CDK5. The cleavage of p35 to p25 is mediated by calpain	SIGNOR-251604
P49841	Q5JTC6	0	relocalization	up-regulates activity	0.419	Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.	SIGNOR-171892
P41594	Q04759	0	phosphorylation	up-regulates activity	0.291	Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.	SIGNOR-249290
Q9UBR4	O75116	0	phosphorylation	up-regulates activity	0.2	Rok-\u03b1 phosphorylates and activates LIM kinase, which in turn phosphorylates and inactivates cofilin.	SIGNOR-280110
Q92769	P19784	0	phosphorylation	up-regulates activity	0.39	HDAC2 is phosphorylated uniquely by protein kinase CK2 in vitro. Studies using unfractionated cell extracts with CK2 inhibitors suggest that protein kinase CK2 is the major source of HDAC2 kinase. Finally, and perhaps most interesting, HDAC2 phosphorylation promotes enzymatic activity, selectively regulates complex formation, but has no effect on transcriptional repression. \| Since our data suggest that protein kinase CK2 is the major kinase responsible for HDAC2 phosphorylation, and because Ser422 and Ser424, but not Ser411, lie within CK2 recognition sequences, we believe that Ser394, Ser422, and Ser424 constitute the three phosphorylated residues in HDAC2.	SIGNOR-251001
Q9P253	Q9NZ52	1	monoubiquitination	down-regulates activity	0.506	Monoubiquitylation of GGA3 by hVPS18 regulates its ubiquitin-binding ability. By in vitro ubiquitylation assays, we have identified lysine 258 in the GAT domain as a major ubiquitylation site that resides adjacent to the ubiquitin-binding site. Furthermore, the GAT domain ubiquitylated by hVPS18 no longer binds to ubiquitin, indicating that ubiquitylation negatively regulates the ubiquitin-binding ability of the GAT domain. These results suggest that the ubiquitin binding and ubiquitylation of GGA3-GAT domain are mutually inseparable through a ubiquitin ligase activity of hVPS18.	SIGNOR-271610
P08069	P25098	0	phosphorylation	down-regulates quantity by destabilization	0.2	GRK2 and GRK6 coimmunoprecipitate with IGF-1R and increase IGF-1R serine phosphorylation, promoting β-arrestin1 association. Using immunoprecipitation, confocal microscopy, and FRET analysis, we demonstrated β-arrestin/IGF-1R association to be transient for GRK2 and stable for GRK6. Using bioinformatic studies we identified serines 1248 and 1291 as the major serine phosphorylation sites of the IGF-1R. Targeted mutation of S1248 recapitulates GRK2 modulation, whereas S1291 mutation resembles GRK6 effects on IGF-1R signaling/degradation	SIGNOR-276413
Q00535	P63167	1	phosphorylation	up-regulates activity	0.2	CDK5 activates the tumor suppressor DLC1 by phosphorylating and diminishing the binding of an autoinhibitory region of DLC1 to its Rho-GAP domain and allows it to localize to focal adhesions.\|Here, we report that CDK5 coordinately activates multiple DLC1 functions, elucidate the mechanism underlying this activation, and identify a role for DLC1 inactivation in the pro oncogenic activity CDK5.	SIGNOR-279154
P04637	Q13315	0	phosphorylation	up-regulates quantity by stabilization	0.843	In response to ionizing radiation (ir), atm, the gene product mutated in ataxia telangiectasia, stabilizes and activates p53 through phosphorylation of ser15 and (indirectly) ser20. Here we show that phosphorylation of p53 on ser46, a residue important for p53 apoptotic activity, as well as on ser9, in response to ir also is dependent on the atm protein kinase. one pathway involves the phosphorylation of p53 and its negative regulator mdm2 by ataxia telangiectasia mutated (atm) and chk2 causing p53 activation and stabilization.	SIGNOR-115348
P19419	P27361	0	phosphorylation	up-regulates	0.601	Erki phosphorylates five c-terminal sites in elk-i (s324, t336, s383, s389 and s422) with varying degrees of efficiency.	SIGNOR-34669
Q9NTX7	Q9H2K2	1	ubiquitination	down-regulates quantity	0.614	We show that RNF146, tankyrase, and Axin form a protein complex, and that RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation.	SIGNOR-260005
P28482	P05023	1	phosphorylation	down-regulates activity	0.519	Parathyroid hormone (PTH) inhibits Na+,K+-ATPase activity through protein kinase C- (PKC) and extracellular signal-regulated kinase- (ERK) dependent pathways and increases serine phosphorylation of the α1-subunit. These results suggest that PTH regulates Na(+),K(+)-ATPase by PKC and ERK-dependent alpha(1)-subunit phosphorylation and that the phosphorylation requires the expression of a serine at the 11 position of the Na(+),K(+)-ATPase alpha(1)-subunit.	SIGNOR-262940
Q71DI3	Q92831	0	acetylation	down-regulates activity	0.2	The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.	SIGNOR-269626
Q00535	P78352	1	phosphorylation	down-regulates activity	0.655	Cdk5 was shown to phosphorylate PSD-95 at three sites, Thr19, Ser25, and Ser35, in PSD fractions, which reduces the ability of PSD-95 to multimerize, resulting in decreased NMDAR clustering (Table 2).	SIGNOR-279152
O15247	Q7Z570	0	transcriptional regulation	down-regulates quantity by repression	0.2	ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3).	SIGNOR-269465
P06493	Q13042	1	phosphorylation	up-regulates	0.638	Apc activation is thought to depend on apc phosphorylation and cdc20 binding. We have identified 43 phospho_sites on apc of which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts of apc1 and the tetratricopeptide repeat (tpr) subunits cdc27, cdc16, cdc23 and apc7. In vitro, at least 15 of the mitotic phospho_sites can be generated by cyclin_dependent kinase 1 (cdk1), and 3 by polo_like kinase 1 (plk1). Apc phosphorylation by cdk1, but not by plk1, is sufficient for increased cdc20 binding and apc activation	SIGNOR-119762
Q9Y6Q9	P00519	0	phosphorylation	up-regulates	0.348	Tyrosine phosphorylation of the nuclear receptor coactivator aib1/src-3 is enhanced by abl kinase and is required for its activity in cancer cellstyrosine kinase directly phosphorylates aib1/src-3 at y1357 and modulates the association of aib1 with c-abl, eralpha, the transcriptional cofactor p300,	SIGNOR-180571
Q9UPZ9	P53041	0	dephosphorylation	down-regulates activity	0.2	MAK and MRK require dual phosphorylation in a TDY motif catalyzed by an unidentified human threonine kinase and tyrosine autophosphorylation.\| Protein phosphatase 5 (PP5) interacts with MRK in a complex and dephosphorylates MRK at T157 in vitro and in situ.	SIGNOR-248541
P08631	P42768	1	phosphorylation	up-regulates activity	0.555	Hck induces tyrosine phosphorylation of WASp. Here we show that the Src family kinase Hck induces phosphorylation of WASp-Tyr(291) independently of Cdc42 and that this causes a shift in the mobility of WASp upon SDS-PAGE. A phospho-mimicking mutant, WASp-Y291E, exhibited an enhanced ability to stimulate actin polymerization in a cell-free system and when microinjected into primary macrophages induced extensive filopodium formation with greater efficiency than wild-type WASp or a Y291F mutant. We propose that phosphorylation of Tyr(291) directly regulates WASp function.	SIGNOR-273957
Q9UKT9	Q96SW2	0	ubiquitination	down-regulates quantity by destabilization	0.581	IMiD compounds cause selective ubiquitination and degradation of IKZF1 in CD34+ cells by the CRBN E3 ubiquitin ligase.	SIGNOR-272319
Q9UQL6	Q14012	0	phosphorylation	down-regulates	0.419	Camk phosphorylates serines -259 and -498 in hdac5, which subsequently serve as docking sites for 14-3-3. Our studies suggest that 14-3-3 binding to hdac5 is required for camk-dependent disruption of mef2hdac complexes and nuclear export of hdac5, and implicate 14-3-3 as a signal-dependent regulator of muscle cell differentiation.	SIGNOR-85022
P51608	P46531	1	transcriptional regulation	down-regulates quantity by repression	0.29	As the first step to reveal how MeCP2 phosphorylation may regulate Notch signaling, we conducted chromatin immunoprecipitation (ChIP) experiment to determine whether the phosphor-mutant MeCP2 protein has altered promoter occupancy at the promoters of Dll1 and Notch1. We found increased binding of the phosphor-mutant protein at the promoters of both Dll1 and Notch1	SIGNOR-264675
Q05682	O75914	0	phosphorylation	down-regulates	0.2	We investigated the effects of phosphorylation by p(21)-activated kinase 3 (pak) and calmodulin on the 22 kda c-terminal fragment of caldesmon (cad22). We substituted the major pak sites, ser-672 and ser-702, with either alanine or aspartic acid to mimic nonphosphorylated and constitutively phosphorylated states of caldesmon, respectively. Phosphorylation at these sites weakened ca(2+)-calmodulin binding further and reduced the inhibitory activity of cad22 in the absence of ca(2+)-calmodulin.	SIGNOR-167976
Q9UJA2	Q9BXM7	0	phosphorylation	down-regulates quantity	0.429	In vitro kinase assays using recombinant proteins under various control conditions indicated that PINK1 directly phosphorylates CLS1 (XREF_FIG).\|Similar to Fbxo15, knockdown of PINK1 kinase using shRNA increased CLS1 levels, whereas overexpression of PINK1 plasmid decreased CLS1 levels .	SIGNOR-280065
P04637	P13611	1	transcriptional regulation	up-regulates quantity by expression	0.29	By using in vitro and in vivo assays, we showed CSPG2 to be directly transactivated by p53.	SIGNOR-255441
P11511	Q13285	0	transcriptional regulation	up-regulates quantity by expression	0.479	The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes.	SIGNOR-271787
Q13546	Q8TE49	0	deubiquitination	down-regulates activity	0.2	NF-kappaB Suppression by the Deubiquitinating Enzyme Cezanne\|Our study provides several lines of evidence to suggest that Cezanne suppresses TNFR signaling to NF-κB by targeting RIP1 for deubiquitination.	SIGNOR-268410
Q8NHV4	O00444	0	phosphorylation	up-regulates activity	0.593	We found that PLK4-mediated phosphorylation of NEDD1 at its S325 amino acid residue directly promotes both NEDD1 binding to SAS-6 and recruiting SAS-6 to the centrosome. \|Collectively, our results demonstrate that PLK4-regulated NEDD1 facilitates initiation of the cartwheel assembly and of daughter centriole biogenesis in mammals.	SIGNOR-272996
P48775	P04150	0	transcriptional regulation	down-regulates quantity by repression	0.337	Repression of GR-mediated expression of the tryptophan oxygenase gene by the SWI/SNF complex during liver development.	SIGNOR-268995
O14920	Q13568	1	phosphorylation	up-regulates activity	0.37	Here we present evidence that the kinase IKKbeta phosphorylates and activates IRF5 in response to stimulation in several inflammatory pathways, including those emanated from Toll like receptors and retinoic acid inducible gene I like receptors.\|Recombinant IKK\u03b2 phosphorylated IRF5 at Ser-445 in vitro, and a point mutation of this serine abolished IRF5 activation and cytokine production.	SIGNOR-279466
Q02078	P12882	1	transcriptional regulation	up-regulates quantity by expression	0.355	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-238748
Q02156	P46459	1	phosphorylation	up-regulates activity	0.234	PKCepsilon phosphorylation enhances the ATPase activity of NSF.\|These results indicate that PKCepsilon phosphorylates NSF at both S460 and T461 in vitro.	SIGNOR-278300
P09874	Q05655	0	phosphorylation	down-regulates activity	0.2	Interestingly, comparable experiments with the Ca 2+ -independent PKC\u03b4 isoform revealed that PKC\u03b4 phosphorylates ARTD1 at the N-terminus (amino acids 1\u2013214) and phosphorylation of ARTD1 by PKC\u03b4 inhibited DNA-induced PAR formation by ARTD1 in vitro (Supplementary Figure S6A and S6B), suggesting that the observed stimulatory effect of the PKCi on PAR formation might be due to inhibition of ARTD1 by PKC\u03b4.	SIGNOR-280085
P68431	Q96T68	0	methylation	up-regulates activity	0.2	Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression.	SIGNOR-263896
P53779	P05412	1	phosphorylation	up-regulates	0.887	With epidermal growth factor treatment, overexpression of erk8 in jb6 cl41 cells caused an increased phosphorylation of c-jun at ser(63) and ser(73), resulting in increased activator protein-1 transactivation.	SIGNOR-164800
Q9NXA8	Q15067	1	catalytic activity	down-regulates activity	0.26	SIRT5‐mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation.	SIGNOR-261210
Q9HCM9	P04637	1	ubiquitination	down-regulates quantity by destabilization	0.351	Furthermore, we show here that the Trim39 can directly bind and ubiquitylate p53 in vitro and in vivo, leading to p53 degradation.	SIGNOR-272020

Q9Y618

Q04206

0

relocalization

down-regulates activity

0.404

Furthermore, overexpression of Flt3-ITD led to a partial relocalization of SMRT protein from the nucleus to the cytoplasm. This indicates that shuttling of p65 was necessary for Flt3-ITD-mediated SMRT nuclear export.

SIGNOR-261539

Q86UZ6

P15018

1

transcriptional regulation

up-regulates quantity by expression

0.2

ZBTB46 binds directly to the LIF regulatory sequence and enhances its transcription. Our study confirmed a novel positive association between ZBTB46 activity and LIF levels in prostate cancer tissues and cells. Under androgen regulation, low levels of ZBTB46 are an essential transcriptional factor for maintaining LIF-STAT3 signaling, while the loss of androgen signaling or inhibition of AR signaling causes LIF-enhanced therapeutic resistance and CRPC characteristics through the upregulation of ZBTB46. We also found that LIF activation drives malignant progression and NE-like reprogramming in prostate cancer by activating STAT3 signaling.

SIGNOR-277988

P06493

Q14980

1

phosphorylation

down-regulates

0.587

Cdk1-mediated phosphorylation at t2055 negatively regulates numa cortical localization and that this phosphorylation is counteracted by ppp2ca phosphatase activity.

SIGNOR-194825

Q14258

O43283

0

phosphorylation

up-regulates quantity by stabilization

0.2

Mechanistically, MAP3K13 phosphorylates the E3 ubiquitin ligase TRIM25 at Ser12 to decrease its polyubiquitination and proteasomal degradation.

SIGNOR-277456

Q4V328

P42574

0

cleavage

up-regulates activity

0.414

These results suggest that the region of GRASP‐1 downstream of the Caspase‐3‐cleavage site is capable of activating the JNK signaling pathway by enhancing the phosphorylation of JNK. these results suggest that full length GRASP‐1 does not enhance JNK pathway activity, possibly due to the inhibitory effect of the N‐terminal fragment on the C‐terminal fragment. In contrast, Caspase‐3 cleavage of GRASP‐1 releases the C‐terminal fragment, which in turn activates JNK signaling by serving as a scaffold protein.

SIGNOR-260641

P49593

Q13177

1

dephosphorylation

down-regulates

0.261

Pop x2, a pp 2c serine/threonine phosphatase, is known to dephosphorylate pak and downregulate its activity.

SIGNOR-162149

Q92831

Q5TEC6

1

acetylation

down-regulates activity

0.2

The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.

SIGNOR-269624

P00519

Q9UPY6

1

phosphorylation

up-regulates activity

0.582

WAVE3-Abl interaction promotes the tyrosine phosphorylation of WAVE3 by Abl, and STI-571, a specific inhibitor of Abl kinase activity, abrogates the Abl-mediated phosphorylation of WAVE3.

SIGNOR-259077

Q9UHD2

A7MCY6

0

relocalization

up-regulates activity

0.603

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

SIGNOR-272469

Q9NRC8

Q9NR30

1

deacetylation

up-regulates activity

0.26

Significantly, the activity of DDX21 is regulated by acetylation. Acetylation by CBP inhibits DDX21 activity, while deacetylation by SIRT7 augments helicase activity and overcomes R-loop-mediated stalling of RNA polymerases.|acetylation of K18, K137, and K600 impairs the helicase activity of DDX21.

SIGNOR-275903

Q92974

O14965

0

phosphorylation

down-regulates activity

0.332

The mitotic kinases Aurora A/B and Cdk1/Cyclin B phosphorylate GEF-H1, thereby inhibiting GEF-H1 catalytic activity.

SIGNOR-276061

Q5VWQ8

Q13309

0

ubiquitination

down-regulates quantity by destabilization

0.267

DAB2IP protein levels can be negatively regulated by the activity of the E3-ubiquitin ligases Fbw7, Skp2, and Smurf1

SIGNOR-254775

P31273

O15550

0

transcriptional regulation

up-regulates quantity by expression

0.307

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

SIGNOR-260029

P49336

Q16695

1

phosphorylation

down-regulates activity

0.2

However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo.

SIGNOR-273175

Q9UI46

Q92949

0

transcriptional regulation

up-regulates quantity by expression

0.368

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

SIGNOR-266932

Q7Z6E9

Q8NAP3

1

ubiquitination

down-regulates quantity by destabilization

0.423

Thus, RBBP6 induces ZBTB38 protein degradation, and this depends on the activity of the proteasome.We next tested whether RBBP6 might directly ubiquitinate ZBTB38.|We show that ZBTB38 is directly ubiquitinated by RBBP6 in human and mouse cells, in a process that is independent of p53 and MDM2, and leads to proteasomal degradation.

SIGNOR-278594

Q00535

Q05397

1

phosphorylation

up-regulates

0.305

Here, we show that fak phosphorylation by cdk5 at s732 is important for microtubule organization, nuclear movement, and neuronal migration. In cultured neurons, s732-phosphorylated fak is enriched along a centrosome-associated microtubule fork that abuts the nucleus. Overexpression of the nonphosphorylatable mutant fak s732a results in disorganization of the microtubule fork and impairment of nuclear movement in vitro, and neuronal positioning defects in vivo.

SIGNOR-86223

Q13882

P40763

1

phosphorylation

up-regulates activity

0.622

29 PTK6 promotes activating phosphorylation of STAT3 at tyrosine residue 705.|STAT3 has been shown to promote tumor initiation of different tumor types, including those of the gastrointestinal tract and skin, and PTK6 was previously shown to promote STAT3 activation and tumorigenesis in mouse models of colon and skin cancer.

SIGNOR-278346

O43164

Q9Y4C4

1

ubiquitination

up-regulates activity

0.403

These results suggest that the ubiquitylation of MFHAS1 by praja2 has a vital role in M1 macrophage polarization and promotes the transformation of M2 macrophages to M1 macrophages through both the JNK and p38 pathways.

SIGNOR-278559

P63104

P11309

0

phosphorylation

up-regulates activity

0.31

PIM1 phosphorylates the AR and 14-3-3 ζ and coordinates their interaction. PIM1 phosphorylation of the AR and 14-3-3 ζ enhances their interaction and shifts their occupancy on chromatin, resulting in 14-3-3 ζ co-regulation of AR, likely by recruiting other AR co-regulators such as hnRNPK and TRIM28.

SIGNOR-277574

Q92830

Q6NXT2

1

acetylation

down-regulates activity

0.2

The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.

SIGNOR-269608

O15355

P63162

1

dephosphorylation

up-regulates quantity by stabilization

0.2

Dephosphorylation of survival motor neurons (SMN) by PPM1G and PP2Cgamma governs Cajal body localization and stability of the SMN complex.|This indicates that the catalytic activity of PPM1G promotes accumulation of the SMN complex in CBs and suggests that PPM1G is a major determinant of the SMN-complex localization in the nucleus.

SIGNOR-277021

P00519

Q14191

1

phosphorylation

up-regulates

0.41

We thus hypothesized that wrn may interact with the abl tyrosine kinase in the dna damage response. Here, we provide evidence for a functional and physical interaction between wrn and c-abl, including wrn relocalization in response to dna damage, suggesting that this protein-protein interaction participates in a shared pathway of genome surveillance.

SIGNOR-86497

Q9UBU7

Q13535

0

phosphorylation

down-regulates

0.657

Dbf4/cdc7 (dbf4-dependent kinase (ddk)) is activated at the onset of s-phase, and its kinase activity is required for dna replication initiation from each origin. We identified novel atm/atr phosphorylation sites on dbf4 and showed that atm/atr-mediated phosphorylation of dbf4 is critical for the intra-s-phase checkpoint to inhibit dna replication.

SIGNOR-177809

Q9Y566

O14490

0

relocalization

up-regulates activity

0.857

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

SIGNOR-264586

Q9UBK2

P31751

0

phosphorylation

down-regulates

0.348

Here we describe a mechanism by which insulin, through the intermediary protein kinase akt2/protein kinase b (pkb)-beta, elicits the phosphorylation and inhibition of the transcriptional coactivator peroxisome proliferator-activated receptor-coactivator 1alpha (pgc-1alpha), a global regulator of hepatic metabolism during fasting / phosphorylation of pgc-1? At ser?570 Is required for akt to inhibit recruitment of pgc-1? To chromatin.

SIGNOR-155536

P31749

Q15942

1

phosphorylation

down-regulates

0.415

Akt binds and phosphorylates zyxin on serine 142, leading to its association with acinus zyxin is a substrate of caspases, but akt phosphorylation fails to protect its proteolytic degradation

SIGNOR-156122

P28482

Q15797

1

phosphorylation

down-regulates

0.608

Phosphorylation of the linker region of smads mediated by erk2, gsk3?, And cdk2/4 negatively regulates smad activity by preventing their relocation to the nucleus, by inhibiting their interactions with coactivators, or by accelerating their degradation;in contrast, erk2 phosphorylated all four smad1 residues almost evenly, while showing a preference for s204 over s208 and s213 in smad3

SIGNOR-161597

Q15797

P35813

0

dephosphorylation

down-regulates

0.538

In this study, we have found that ppm1a, a metal ion-dependent protein serine/threonine phosphatase, physically interacts with and dephosphorylates smad1 both in vitro and in vivo. considering the highly conserved nature of the sxs motif in all r-smads, we reasoned that ppm1a might also recognize the sxs motif in the bmp-activated smad1.

SIGNOR-149077

P45984

P35568

1

phosphorylation

down-regulates

0.706

Map kinases and mtor mediate insulin-induced phosphorylation ofinsulinreceptor substrate-1 on serine residues 307, 612 and 632

SIGNOR-118877

P17612

P13796

1

phosphorylation

up-regulates

0.327

Phosphorylation on ser5 increases the f-actin-binding activity of l-plastin and promotes its targeting to sites of actin assembly in cells. L-plastin phosphorylation require protein kinase a.

SIGNOR-146287

P17252

Q96PY5

1

phosphorylation

up-regulates activity

0.2

PKCα associates with and phosphorylates FMNL2 at S1072 within its Diaphanous autoregulatory region, leading to the release of formin autoinhibition.

SIGNOR-273796

P43268

Q15831

0

phosphorylation

down-regulates quantity by destabilization

0.622

LKB1 phosphorylated PEA3 and promoted its degradation through a proteasome-mediated mechanism.

SIGNOR-279293

Q99497

Q8IW41

0

phosphorylation

up-regulates activity

0.469

PRAK preferentially colocalizes with DJ-1 and leads to DJ-1 activation, which in turn facilitates DJ-1 to sequester Daxx in the nucleus, preventing oxidative stress induced cell death.|These data clearly demonstrate a PRAK dependent phosphorylation of DJ-1.

SIGNOR-279746

P06239

P27986

1

phosphorylation

down-regulates activity

0.623

the regulatory p85 subunit of phosphatidylinositol 3-kinase is phosphorylated on tyrosine residues. We report that this phosphorylation event is readily catalyzed by the Abl and Lck protein-tyrosine kinases in vitro, by Bcr-Abl or a catalytically activated Lck-Y505F in co-transfected COS cells. we have mapped a major phosphorylation site to Tyr-688 in the C-terminal SH2 domain of p85. Tyrosine phosphorylation of p85 in vitro or in vivo was not associated with detectable change in the enzymatic activity of the phosphatidylinositol 3-kinase heterodimer, but correlated with a strong reduction in the binding of some, but not all, phosphoproteins to the SH2 domains of p85.

SIGNOR-251383

O00308

P48431

1

ubiquitination

down-regulates quantity

0.361

Among the four E3 ligases, only WWP2 knockdown was found to increase SOX2 protein levels in GSCs (Fig.\u00a04A).|We first verified that WWP2 ubiquitinates SOX2 in vitro.

SIGNOR-278798

O00213

P49841

0

phosphorylation

up-regulates quantity

0.293

In this regards, GSK3beta may promote amyloidogenic processing of APP by regulating the cellular level of monomeric FE65 for the formation of LRP1, FE65, and APP complex.|In this study, we showed that FE65 is phosphorylated at T579 by GSK3beta.

SIGNOR-278359

Q8WU17

O15503

1

ubiquitination

down-regulates quantity

0.477

TRC8/RNF139 encodes an endoplasmic reticulum-resident E3 ubiquitin ligase that inhibits growth in a RING- and ubiquitylation-dependent manner. TRC8 also contains a predicted sterol-sensing domain. Here, we report that TRC8 protein levels are sterol responsive and that it binds and stimulates ubiquitylation of the endoplasmic reticulum anchor protein INSIG. Thus, we conclude that INSIG-1 and 2 physically interact with TRC8, and that TRC8 enhances ubiquitylation of INSIG-1 in a RING-dependent manner

SIGNOR-271955

Q96EP1

P53350

1

polyubiquitination

down-regulates quantity by destabilization

0.468

Chfr, a mitotic stress checkpoint, plays an important role in cell cycle progression, tumor suppression and the processes that require the E3 ubiquitin ligase activity mediated by the RING finger domain. Chfr stimulates the formation of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins including Plk1 and Aurora A.

SIGNOR-271464

P38936

O14757

0

phosphorylation

down-regulates quantity by destabilization

0.531

Responsible for this degradation is the checkpoint kinase Chk1, which phosphorylates p21(Waf1) on T145 and S146 residues and induces its proteasome-dependent proteolysis.

SIGNOR-279325

Q9UBK2

Q13131

0

phosphorylation

up-regulates activity

0.575

Ampk phosphorylates pgc-1alpha directly both in vitro and in cells. These direct phosphorylations of the pgc-1alpha protein at threonine-177 and serine-538.

SIGNOR-156780

P51946

P49336

0

phosphorylation

down-regulates

0.645

Cdk8 phosphorylates mammalian cyclin h in the vicinity of its functionally unique amino-terminal and carboxy-terminal alpha-helical domains. This phosphorylation represses both the ability of tfiih to activate transcription and its ctd kinase activity

SIGNOR-82033

Q9UNI6

Q99683

1

dephosphorylation

down-regulates activity

0.25

Our study showed that DUSP12 inhibited ASK1-JNK activation and DUSP12 can directly bind to and dephosphorylate ASK1.

SIGNOR-277032

P55011

Q9BYP7

0

phosphorylation

up-regulates activity

0.525

We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs

SIGNOR-264625

O75534

P35637

0

post transcriptional regulation

up-regulates quantity by stabilization

0.2

These findings demonstrated that LINC00205 facilitates malignant phenotypes in LC by recruiting FUS to stabilize CSDE1, suggesting LINC00205 as a potential target for LC therapy.|Subsequent RIP assay con- firmed such prediction, as CSDE1 mRNA was evidently precipitated by anti-FUS (Figure 3A).

SIGNOR-262110

P27361

Q8IVS8

1

phosphorylation

up-regulates quantity by stabilization

0.2

Mechanistically, glucose deprivation-activated ERK1 phosphorylates GLYCTK2 at serine 220 directly, which prevents STUB1 (ubiquitin E3 ligase) binding, thereby abrogating the ubiquitination and degradation of GLYCTK2. ERK1 phosphorylates GLYCTK2 at S220 to promotes its stability

SIGNOR-280257

P41235

P04150

0

transcriptional regulation

up-regulates quantity by expression

0.37

Electrophoretic mobility shift, chromatin immunoprecipitation (ChIP), and streptavidin DNA binding assays revealed that DEX increased binding of HNF4alpha to the HNF4-RE and that an interaction of GR and HNF4alpha occurred at this site.

SIGNOR-251684

O95155

P10636

1

ubiquitination

down-regulates quantity by destabilization

0.2

Ubiquitination and degradation of Tau by UBE4B and STUB1 in mammalian neuroblastoma cells.

SIGNOR-278682

P06239

P15941

1

phosphorylation

up-regulates activity

0.46

The present results demonstrate that Lck phosphorylation of MUC1 on Y-46 also increases binding of MUC1 and beta-catenin. The results further show that ZAP-70 phosphorylation of MUC1-CD stimulates the interaction of MUC1 and beta-catenin

SIGNOR-249358

Q9UD71

P68400

0

phosphorylation

up-regulates activity

0.34

Study of [Plphosphate release during manual Edman degradation confirmed that the phosphorylated residues in rat DARPP-32 were Ser45 and Ser102. | Phosphorylation by casein kinase II did not affect the potency of DARPP-32 as an inhibitor of protein phosphatase-1, which depended only on phosphorylation of Thr34 by cAMP-dependent protein kinase. However, phosphorylation of DARPP-32 by casein kinase II facilitated phosphorylation of Thr34 by cAMP-dependent protein kinase

SIGNOR-250927

Q16649

P08700

1

transcriptional regulation

up-regulates quantity by expression

0.527

NF-IL3A transactivates the IL-3 promoter through the A region sequences.

SIGNOR-266222

P43629

Q02156

0

phosphorylation

down-regulates

0.2

Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of ser(394) by protein kinase c slightly suppresses kir3dl1 inhibitory function, and reduces receptor internalization and turnover.

SIGNOR-158129

Q02763

Q03112

0

transcriptional regulation

up-regulates quantity by expression

0.2

We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2

SIGNOR-266063

Q13464

P61587

1

phosphorylation

up-regulates

0.707

We show that rock phosphorylates endogenous rhoe at serine 11 upon cell stimulation with platelet-derived growth factor. Phosphorylation has no effect on rhoe binding to rock i, but instead increases rhoe protein stability.

SIGNOR-134703

P53350

Q8N3U4

1

dephosphorylation

down-regulates activity

0.737

Two phosphorylation sites in Scc1 (Thr144 and Thr312) match the consensus proposed by Nakajima et al. [24]. These two sites, in addition to one in Scc1 (Ser454) and three in SA2 (Thr1109, Ser1137, and Ser1224) conform with the consensus proposed by Barr et al. [25]. These findings are consistent with the possibility that at least some of the sites in Scc1 and SA2 are directly phosphorylated by Plk1.|Phosphorylation of SA2 Is Essential for the Dissociation of Cohesin from Chromosomes during Prophase and Prometaphase

SIGNOR-275534

Q92793

P04637

1

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

P31270

O15550

0

transcriptional regulation

up-regulates quantity by expression

0.263

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

SIGNOR-260021

P30679

Q13794

0

phosphorylation

up-regulates activity

0.2

Ga16 is phosphorylated in vivo by PMA and by TRH receptor stimulation

SIGNOR-278131

P17612

P42858

1

phosphorylation

down-regulates quantity by destabilization

0.2

Moreover, phosphorylation of C-HEAT Ser2550 by cAMP-dependent protein kinase (PKA), the top hit in kinase activity screens, was found to hasten huntingtin degradation, such that levels of the catalytic subunit (PRKACA) were inversely related to huntingtin levels.

SIGNOR-277625

P53779

P14778

0

phosphorylation

up-regulates activity

0.2

Il-1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated mitogen-activated protein (map) kinases, c-jun nh2-terminal kinase (jnk) and p38 map kinase, as well as transcription factor nuclear factor kappab (nf-kappab

SIGNOR-249515

P28562

Q09472

0

acetylation

up-regulates

0.309

A recent report shows that mkp1 may also be regulated by acetylation. When raw macrophages are stimulated with lps, mkp1 becomes acetylated on lys57 by p300

SIGNOR-166581

P28482

P10828

1

phosphorylation

down-regulates activity

0.412

We concluded that serine 142 of the tr dbd is the likely site of phosphorylation by t(4)-activated mapk and that the docking site on tr for activated mapk includes residues 128-133 (kgffrr), a basic amino acid-enriched motif novel for mapk substrates. Tr mutations in the proposed mapk docking domain and at residue 142 modulated t(4)-conditioned shedding of co-repressor and recruitment of co-activator proteins by the receptor, and they altered transcriptional activity of tr in a thyroid hormone response element-luciferase reporter assay.

SIGNOR-102216

Q01196

Q00534

0

phosphorylation

up-regulates

0.615

We have identified four phosphorylation sites on aml1c that are necessary for transcriptional activity of aml1c in k562 and 293t cells (27).4 mutation of these four sites (serine 276, serine 293, serine 303, and threonine 300) to alanine abolishes transcriptional activation, whereas mutation of these sites to aspartic acid (which mimics phosphorylation) results in a hyperactive protein.

SIGNOR-138953

Q15078

P20807

0

cleavage

up-regulates activity

0.261

Calpains also modulate the activity of CDK5. Physiologically, CDK 5 is activated by p35 and its cleaved product p25. The latter has a longer half life than p35 and therefore it is a more potent activator of CDK5. The cleavage of p35 to p25 is mediated by calpain

SIGNOR-251604

P49841

Q5JTC6

0

relocalization

up-regulates activity

0.419

Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.

SIGNOR-171892

P41594

Q04759

0

phosphorylation

up-regulates activity

0.291

Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.

SIGNOR-249290

Q9UBR4

O75116

0

phosphorylation

up-regulates activity

0.2

Rok-\u03b1 phosphorylates and activates LIM kinase, which in turn phosphorylates and inactivates cofilin.

SIGNOR-280110

Q92769

P19784

0

phosphorylation

up-regulates activity

0.39

HDAC2 is phosphorylated uniquely by protein kinase CK2 in vitro. Studies using unfractionated cell extracts with CK2 inhibitors suggest that protein kinase CK2 is the major source of HDAC2 kinase. Finally, and perhaps most interesting, HDAC2 phosphorylation promotes enzymatic activity, selectively regulates complex formation, but has no effect on transcriptional repression. | Since our data suggest that protein kinase CK2 is the major kinase responsible for HDAC2 phosphorylation, and because Ser422 and Ser424, but not Ser411, lie within CK2 recognition sequences, we believe that Ser394, Ser422, and Ser424 constitute the three phosphorylated residues in HDAC2.

SIGNOR-251001

Q9P253

Q9NZ52

1

monoubiquitination

down-regulates activity

0.506

Monoubiquitylation of GGA3 by hVPS18 regulates its ubiquitin-binding ability. By in vitro ubiquitylation assays, we have identified lysine 258 in the GAT domain as a major ubiquitylation site that resides adjacent to the ubiquitin-binding site. Furthermore, the GAT domain ubiquitylated by hVPS18 no longer binds to ubiquitin, indicating that ubiquitylation negatively regulates the ubiquitin-binding ability of the GAT domain. These results suggest that the ubiquitin binding and ubiquitylation of GGA3-GAT domain are mutually inseparable through a ubiquitin ligase activity of hVPS18.

SIGNOR-271610

P08069

P25098

0

phosphorylation

down-regulates quantity by destabilization

0.2

GRK2 and GRK6 coimmunoprecipitate with IGF-1R and increase IGF-1R serine phosphorylation, promoting β-arrestin1 association. Using immunoprecipitation, confocal microscopy, and FRET analysis, we demonstrated β-arrestin/IGF-1R association to be transient for GRK2 and stable for GRK6. Using bioinformatic studies we identified serines 1248 and 1291 as the major serine phosphorylation sites of the IGF-1R. Targeted mutation of S1248 recapitulates GRK2 modulation, whereas S1291 mutation resembles GRK6 effects on IGF-1R signaling/degradation

SIGNOR-276413

Q00535

P63167

1

phosphorylation

up-regulates activity

0.2

CDK5 activates the tumor suppressor DLC1 by phosphorylating and diminishing the binding of an autoinhibitory region of DLC1 to its Rho-GAP domain and allows it to localize to focal adhesions.|Here, we report that CDK5 coordinately activates multiple DLC1 functions, elucidate the mechanism underlying this activation, and identify a role for DLC1 inactivation in the pro oncogenic activity CDK5.

SIGNOR-279154

P04637

Q13315

0

phosphorylation

up-regulates quantity by stabilization

0.843

In response to ionizing radiation (ir), atm, the gene product mutated in ataxia telangiectasia, stabilizes and activates p53 through phosphorylation of ser15 and (indirectly) ser20. Here we show that phosphorylation of p53 on ser46, a residue important for p53 apoptotic activity, as well as on ser9, in response to ir also is dependent on the atm protein kinase. one pathway involves the phosphorylation of p53 and its negative regulator mdm2 by ataxia telangiectasia mutated (atm) and chk2 causing p53 activation and stabilization.

SIGNOR-115348

P19419

P27361

0

phosphorylation

up-regulates

0.601

Erki phosphorylates five c-terminal sites in elk-i (s324, t336, s383, s389 and s422) with varying degrees of efficiency.

SIGNOR-34669

Q9NTX7

Q9H2K2

1

ubiquitination

down-regulates quantity

0.614

We show that RNF146, tankyrase, and Axin form a protein complex, and that RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation.

SIGNOR-260005

P28482

P05023

1

phosphorylation

down-regulates activity

0.519

Parathyroid hormone (PTH) inhibits Na+,K+-ATPase activity through protein kinase C- (PKC) and extracellular signal-regulated kinase- (ERK) dependent pathways and increases serine phosphorylation of the α1-subunit. These results suggest that PTH regulates Na(+),K(+)-ATPase by PKC and ERK-dependent alpha(1)-subunit phosphorylation and that the phosphorylation requires the expression of a serine at the 11 position of the Na(+),K(+)-ATPase alpha(1)-subunit.

SIGNOR-262940

Q71DI3

Q92831

0

acetylation

down-regulates activity

0.2

The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.

SIGNOR-269626

Q00535

P78352

1

phosphorylation

down-regulates activity

0.655

Cdk5 was shown to phosphorylate PSD-95 at three sites, Thr19, Ser25, and Ser35, in PSD fractions, which reduces the ability of PSD-95 to multimerize, resulting in decreased NMDAR clustering (Table 2).

SIGNOR-279152

O15247

Q7Z570

0

transcriptional regulation

down-regulates quantity by repression

0.2

ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3).

SIGNOR-269465

P06493

Q13042

1

phosphorylation

up-regulates

0.638

Apc activation is thought to depend on apc phosphorylation and cdc20 binding. We have identified 43 phospho_sites on apc of which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts of apc1 and the tetratricopeptide repeat (tpr) subunits cdc27, cdc16, cdc23 and apc7. In vitro, at least 15 of the mitotic phospho_sites can be generated by cyclin_dependent kinase 1 (cdk1), and 3 by polo_like kinase 1 (plk1). Apc phosphorylation by cdk1, but not by plk1, is sufficient for increased cdc20 binding and apc activation

SIGNOR-119762

Q9Y6Q9

P00519

0

phosphorylation

up-regulates

0.348

Tyrosine phosphorylation of the nuclear receptor coactivator aib1/src-3 is enhanced by abl kinase and is required for its activity in cancer cellstyrosine kinase directly phosphorylates aib1/src-3 at y1357 and modulates the association of aib1 with c-abl, eralpha, the transcriptional cofactor p300,

SIGNOR-180571

Q9UPZ9

P53041

0

dephosphorylation

down-regulates activity

0.2

MAK and MRK require dual phosphorylation in a TDY motif catalyzed by an unidentified human threonine kinase and tyrosine autophosphorylation.| Protein phosphatase 5 (PP5) interacts with MRK in a complex and dephosphorylates MRK at T157 in vitro and in situ.

SIGNOR-248541

P08631

P42768

1

phosphorylation

up-regulates activity

0.555

Hck induces tyrosine phosphorylation of WASp. Here we show that the Src family kinase Hck induces phosphorylation of WASp-Tyr(291) independently of Cdc42 and that this causes a shift in the mobility of WASp upon SDS-PAGE. A phospho-mimicking mutant, WASp-Y291E, exhibited an enhanced ability to stimulate actin polymerization in a cell-free system and when microinjected into primary macrophages induced extensive filopodium formation with greater efficiency than wild-type WASp or a Y291F mutant. We propose that phosphorylation of Tyr(291) directly regulates WASp function.

SIGNOR-273957

Q9UKT9

Q96SW2

0

ubiquitination

down-regulates quantity by destabilization

0.581

IMiD compounds cause selective ubiquitination and degradation of IKZF1 in CD34+ cells by the CRBN E3 ubiquitin ligase.

SIGNOR-272319

Q9UQL6

Q14012

0

phosphorylation

down-regulates

0.419

Camk phosphorylates serines -259 and -498 in hdac5, which subsequently serve as docking sites for 14-3-3. Our studies suggest that 14-3-3 binding to hdac5 is required for camk-dependent disruption of mef2hdac complexes and nuclear export of hdac5, and implicate 14-3-3 as a signal-dependent regulator of muscle cell differentiation.

SIGNOR-85022

P51608

P46531

1

transcriptional regulation

down-regulates quantity by repression

0.29

As the first step to reveal how MeCP2 phosphorylation may regulate Notch signaling, we conducted chromatin immunoprecipitation (ChIP) experiment to determine whether the phosphor-mutant MeCP2 protein has altered promoter occupancy at the promoters of Dll1 and Notch1. We found increased binding of the phosphor-mutant protein at the promoters of both Dll1 and Notch1

SIGNOR-264675

Q05682

O75914

0

phosphorylation

down-regulates

0.2

We investigated the effects of phosphorylation by p(21)-activated kinase 3 (pak) and calmodulin on the 22 kda c-terminal fragment of caldesmon (cad22). We substituted the major pak sites, ser-672 and ser-702, with either alanine or aspartic acid to mimic nonphosphorylated and constitutively phosphorylated states of caldesmon, respectively. Phosphorylation at these sites weakened ca(2+)-calmodulin binding further and reduced the inhibitory activity of cad22 in the absence of ca(2+)-calmodulin.

SIGNOR-167976

Q9UJA2

Q9BXM7

0

phosphorylation

down-regulates quantity

0.429

In vitro kinase assays using recombinant proteins under various control conditions indicated that PINK1 directly phosphorylates CLS1 (XREF_FIG).|Similar to Fbxo15, knockdown of PINK1 kinase using shRNA increased CLS1 levels, whereas overexpression of PINK1 plasmid decreased CLS1 levels .

SIGNOR-280065

P04637

P13611

1

transcriptional regulation

up-regulates quantity by expression

0.29

By using in vitro and in vivo assays, we showed CSPG2 to be directly transactivated by p53.

SIGNOR-255441

P11511

Q13285

0

transcriptional regulation

up-regulates quantity by expression

0.479

The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes.

SIGNOR-271787

Q13546

Q8TE49

0

deubiquitination

down-regulates activity

0.2

NF-kappaB Suppression by the Deubiquitinating Enzyme Cezanne|Our study provides several lines of evidence to suggest that Cezanne suppresses TNFR signaling to NF-κB by targeting RIP1 for deubiquitination.

SIGNOR-268410

Q8NHV4

O00444

0

phosphorylation

up-regulates activity

0.593

We found that PLK4-mediated phosphorylation of NEDD1 at its S325 amino acid residue directly promotes both NEDD1 binding to SAS-6 and recruiting SAS-6 to the centrosome. |Collectively, our results demonstrate that PLK4-regulated NEDD1 facilitates initiation of the cartwheel assembly and of daughter centriole biogenesis in mammals.

SIGNOR-272996

P48775

P04150

0

transcriptional regulation

down-regulates quantity by repression

0.337

Repression of GR-mediated expression of the tryptophan oxygenase gene by the SWI/SNF complex during liver development.

SIGNOR-268995

O14920

Q13568

1

phosphorylation

up-regulates activity

0.37

Here we present evidence that the kinase IKKbeta phosphorylates and activates IRF5 in response to stimulation in several inflammatory pathways, including those emanated from Toll like receptors and retinoic acid inducible gene I like receptors.|Recombinant IKK\u03b2 phosphorylated IRF5 at Ser-445 in vitro, and a point mutation of this serine abolished IRF5 activation and cytokine production.

SIGNOR-279466

Q02078

P12882

1

transcriptional regulation

up-regulates quantity by expression

0.355

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-238748

Q02156

P46459

1

phosphorylation

up-regulates activity

0.234

PKCepsilon phosphorylation enhances the ATPase activity of NSF.|These results indicate that PKCepsilon phosphorylates NSF at both S460 and T461 in vitro.

SIGNOR-278300

P09874

Q05655

0

phosphorylation

down-regulates activity

0.2

Interestingly, comparable experiments with the Ca 2+ -independent PKC\u03b4 isoform revealed that PKC\u03b4 phosphorylates ARTD1 at the N-terminus (amino acids 1\u2013214) and phosphorylation of ARTD1 by PKC\u03b4 inhibited DNA-induced PAR formation by ARTD1 in vitro (Supplementary Figure S6A and S6B), suggesting that the observed stimulatory effect of the PKCi on PAR formation might be due to inhibition of ARTD1 by PKC\u03b4.

SIGNOR-280085

P68431

Q96T68

0

methylation

up-regulates activity

0.2

Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression.

SIGNOR-263896

P53779

P05412

1

phosphorylation

up-regulates

0.887

With epidermal growth factor treatment, overexpression of erk8 in jb6 cl41 cells caused an increased phosphorylation of c-jun at ser(63) and ser(73), resulting in increased activator protein-1 transactivation.

SIGNOR-164800

Q9NXA8

Q15067

1

catalytic activity

down-regulates activity

0.26

SIRT5‐mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation.

SIGNOR-261210

Q9HCM9

P04637

1

ubiquitination

down-regulates quantity by destabilization

0.351

Furthermore, we show here that the Trim39 can directly bind and ubiquitylate p53 in vitro and in vivo, leading to p53 degradation.

SIGNOR-272020