GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q9HBH9	P28482	0	phosphorylation	up-regulates	0.6	We have identified a new subfamily of murine serine/threonine kinases, whose members, map kinase-interacting kinase 1 (mnk1) and mnk2, bind tightly to the growth factor-regulated map kinases, erk1 and erk2erk and p38 phosphorylate mnk1 and mnk2, which stimulates their in vitro kinase activity	SIGNOR-48338
Q9UHD2	P42345	1	phosphorylation	up-regulates activity	0.42	They later demonstrated that TANK-binding kinase 1 (TBK1) interacts with and phosphorylates mTOR on Ser 2159, to promote catalytic activity of mTOR [216].	SIGNOR-278237
P35637	Q99873	0	methylation	down-regulates activity	0.485	PRMT1 catalyzes the arginine methylation of Fused in Sarcoma (FUS), an RNA-binding protein that interacts with RALY. We demonstrate that RALY down-regulation decreases protein arginine N-methyltransferase 1 levels, thus reducing FUS methylation. It is known that mutations in the FUS nuclear localization signal (NLS) retain the protein to the cytosol, promote aggregate formation, and are associated with amyotrophic lateral sclerosis.	SIGNOR-262274
Q16539	P35638	1	phosphorylation	up-regulates activity	0.61	CHOP, a member of the C/EBP family of transcription factors, mediates effects of cellular stress on growth and differentiation. It accumulates under conditions of stress and undergoes inducible phosphorylation on two adjacent serine residues (78 and 81). In vitro, CHOP is phosphorylated on these residues by p38 mitogen-activated protein kinase (MAP kinase).	SIGNOR-250096
P35968	Q05397	1	null	up-regulates activity	0.496	Here we show that genetic or pharmacological FAK inhibition in ECs prevents VEGF-stimulated permeability downstream of VEGF receptor or Src tyrosine kinase activation in vivo. VEGF promotes tension-independent FAK activation	SIGNOR-261945
O95551	P36896	0	phosphorylation	up-regulates activity	0.28	ALK4 phosphorylated TTRAP in vitro (Fig. 6A). The band migrating at the position of TTRAP was excised and analyzed by LC-MS/MS. One TTRAP peptide was phosphorylated either on T88 and T92, or on T92 only (Fig. 6B).We tested in vivo phosphorylation of Strep-TTRAP by co-expression with mouse Alk4 in HEK293T cells, and affinity-purified TTRAP. In this preparation TTRAP-specific peptides were reproducibly found in both the singly (T92) and doubly phosphorylated form (T88/T92). mutant TTRAPT88A,T92A is not able to rescue the TtrapMO phenotype, suggesting that phosphorylation of Ttrap on Thr88 and Thr92 is essential for Ttrap function.	SIGNOR-262612
P06241	O75553	1	phosphorylation	down-regulates activity	0.614	Tyrosine phosphorylation of Dab1 by Fyn inhibits its interaction with APP, while increasing its interaction with Fyn.	SIGNOR-278476
P25963	Q12923	0	dephosphorylation	up-regulates quantity by stabilization	0.442	Identification of IkappaBalpha as a substrate of Fas-associated phosphatase-1\|A full-length FAP-1 protein preferentially dephosphorylates Tyr-42 of IkBa\|Moreover, other studies have shown that tyrosine phosphorylation of IkBa on Tyr-42 (which occurs with Fas ligand binging) protected against inducible degradation both in vitro [30] and in vivo [38]	SIGNOR-248712
Q13233	O14920	1	phosphorylation	up-regulates activity	0.595	These results suggested that IKK\u03b2 was a likely substrate for MEKK1 and that MEKK1 phosphorylation of IKK\u03b2 increased its kinase activity.	SIGNOR-279339
Q14653	Q9BZ95	0	methylation	up-regulates activity	0.2	We found that lysine methyltransferase NSD3 interacts with and directly monomethylates IRF3 in the nucleus, leading to the enhanced IRF3 transcriptional activity and antiviral immune responses.	SIGNOR-259198
Q12913	P06213	1	dephosphorylation	down-regulates	0.304	Dephosphorylation of autophosphorylated insulin and epidermal-growth-factor receptors by two major subtypes of protein-tyrosine-phosphatase from human placenta.	SIGNOR-21295
P43405	Q13422	1	phosphorylation	up-regulates	0.404	Syk phoshorylatesikarosat unique c-terminal serine phosphorylation sites s358 and s361, thereby augmenting its nuclear localization and sequence-specific dna binding activity. Mechanistically, we establish that syk-inducedikarosactivation is essential for its nuclear localization and optimal transcription factor function.	SIGNOR-199100
Q13153	Q8IYU2	1	phosphorylation	down-regulates activity	0.2	Using a proteomic approach, we identified serine 385 as a target of group-I PAK kinases […] We have established in vitro that HACE1 is a direct target of PAK1 kinase activity.	SIGNOR-255537
Q13153	Q13352	1	phosphorylation	up-regulates	0.2	Serine 28 phosphorylation of nrif3 confers its co-activator function for estrogen receptor-alpha transactivation. p21-activated protein kinase 1 (pak1) phosphorylates eralpha at ser305 and this modification is important in eralpha transactivation function.	SIGNOR-178795
Q9Y4K3	Q9UNE7	0	ubiquitination	down-regulates quantity by destabilization	0.466	CHIP promotes TRAF6 ubiquitination and degradation.\|These results suggest that CHIP negatively regulates the stability of TRAF6.	SIGNOR-278670
P03956	P02458	1	cleavage	down-regulates quantity by destabilization	0.445	MMP-1 cleaves type II collagen at the peptide bond Gly906-Leu907 Proteolysis of triple-helical collagen is an important step in the progression toward irreversible tissue damage in osteoarthritis. Earlier work on the expression of enzymes in cartilage suggested that collagenase-1 (MMP-1) contributes to the process.	SIGNOR-256341
Q00987	P61254	1	ubiquitination	down-regulates quantity by destabilization	0.498	In addition, Mdm2 ubiquitylates L26, leading to its proteasome-mediated degradation.\|We now report that Mdm2 regulates p53 levels also by targeting ribosomal protein L26.	SIGNOR-278828
P59595	P35354	1	transcriptional regulation	up-regulates activity	0.2	SARS-CoV N protein activates COX-2 promoter and induces COX-2 protein expression	SIGNOR-262314
P41181	Q07002	0	phosphorylation	down-regulates quantity by destabilization	0.26	CDK18 controls AQP2 through phosphorylation at serine 261 and STUB1-mediated ubiquitination. \|We had previously observed that a decrease in the phosphorylation of AQP2 at S261 is associated with a decrease in its poly-ubiquitination and an increase in its abundance	SIGNOR-264562
P12931	Q99835	0	phosphorylation	up-regulates	0.436	Instead, shh rapidly and locally stimulated phosphorylation of the src family kinase (sfk) members src and fyn in a smo-dependent fashion.	SIGNOR-178610
P49137	Q14134	1	phosphorylation	up-regulates activity	0.307	ATDC was phosphorylated directly by MAPKAP kinase 2 (MK2) at Ser550 in an ATM-dependent manner. Phosphorylation at Ser-550 by MK2 was required for the radioprotective function of ATDC.	SIGNOR-273675
P06239	P43403	1	phosphorylation	up-regulates activity	0.619	We show that ZAP-70 has a primary autophosphorylation site at Tyr-292, with a secondary site at Tyr-126. We also show additional phosphorylation at Tyr-69, Tyr-178, Tyr-492, and Tyr-493 upon the addition of the protein tyrosine kinase, p56lck	SIGNOR-249375
P51955	Q76N32	1	phosphorylation	down-regulates quantity by destabilization	0.251	In this study we show phosphorylation of Cep68 by Nek2 creates a potential phosphodegron that directs Cep68 destruction through the activity of SCF-beta-Trcp.\|Our above results showed that Nek2 promoted mitotic degradation of Cep68.	SIGNOR-279471
Q9UHH9	P68400	0	phosphorylation	down-regulates quantity by destabilization	0.255	CK2 physiologically phosphorylates IP6K2 at amino acid residues S347 and S356 contained within a PEST sequence, a consensus site for ubiquitination. HCT116 cells depleted of IP6K2 are resistant to cell death elicited by CK2 inhibitors. CK2 phosphorylation at the degradation motif of IP6K2 enhances its ubiquitination and subsequent degradation.	SIGNOR-273625
Q9NW38	P35222	1	ubiquitination	up-regulates activity	0.2	Here we provide evidence that FANCL increases the activity and expression of beta-catenin, a key pluripotency factor in hematopoietic stem cells.\|We show that FANCL ubiquitinates \u03b2-catenin with atypical ubiquitin chain extension known to have nonproteolytic functions.	SIGNOR-278651
P54132	P33981	0	phosphorylation	up-regulates activity	0.315	Moreover, in mitosis, TTK promotes phosphorylation of Bloom syndrome protein (BLM) and subsequent interaction of BLM with PLK1, ensuring accurate chromosome segregation xref .\|Moreover, in mitosis, TTK promotes phosphorylation of Bloom syndrome protein and subsequent interaction of Bloom syndrome protein with PLK1, ensuring accurate chromosome segregation .	SIGNOR-280156
P16284	P07332	0	phosphorylation	up-regulates activity	0.276	PECAM-1 Is Phosphorylated by Fer and, To a Lesser Extent, by Fes. These results suggest that Fer not only functions as a tyrosine kinase for PECAM-1 but also that Fer modulates the downstream signaling of PECAM-1 by inducing phosphorylation of SHP-2 and Gab1.	SIGNOR-262868
P17612	Q7Z2W7	1	phosphorylation	up-regulates activity	0.2	Using specific pharmacological and molecular tools combined with patch-clamp current recordings, we found that in heterologously expressed HEK-293 (human embryonic kidney) cells, TRPM8 channel is inhibited by the G(i) protein/adenylate cyclase (AC)/cAMP/protein kinase A (PKA) signaling cascade. We further identified the TRPM8 S9 and T17 as two key PKA phosphorylation sites regulating TRPM8 channel activity. the intracellular serine/threonine protein phosphatase 2A (PP2A) dephosphorylates TRPM8 Ser-9 and Thr-17 inhibiting the channel activity.	SIGNOR-273791
Q13153	P52565	1	phosphorylation	down-regulates	0.611	Pak1 binds and phosphorylates rhogdi both in vitro and in vivo at ser101 and ser174. This resulted in dissociation of rac1-rhogdi, but not rhoa-rhogdi, complexes, as determined by in vitro assays of complexation and in vivo by coimmunoprecipitation analysis. We observed that cdc42-induced rac1 activation is inhibited by expression of pak1 autoinhibitory domain. The dissociation of rac1 from rhogdi and its subsequent activation stimulated by pdgf or egf is also attenuated by pak1 autoinhibitory domain, and this is dependent on the ability of rhogdi to be phosphorylated at ser101/174.	SIGNOR-126654
Q96GX5	P56211	1	phosphorylation	up-regulates activity	0.73	We identified cyclic adenosine monophosphateregulated phosphoprotein 19 (Arpp19) and -Endosulfine as two substrates of Gwl that, when phosphorylated by this kinase, associate with and inhibit PP2A, thus promoting mitotic entry.	SIGNOR-243611
Q12778	Q13627	0	phosphorylation	down-regulates	0.506	Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity.	SIGNOR-183670
Q14774	P14635	1	transcriptional regulation	up-regulates quantity by expression	0.2	In this study, we have identified cell cycle regulatory genes as downstream targets of the homeobox gene HLX in cultured trophoblast cells, namely RB1, MYC, EGR1, CDKN1C, ELK1, CCNB1, and JUN. RB1 and MYC mRNA expression was increased with HLX inactivation, whereas EGR1, CDKN1C, ELK1, CCNB1, and JUN mRNA expression was decreased compared with mock-transfected control cells.	SIGNOR-261619
P46934	Q13571	1	ubiquitination	up-regulates activity	0.476	These results suggest that LAPTM5 ubiquitination is mediated by Nedd4.\|Thus, Nedd4 promotes the recruitment of GGA3 to LAPTM5, allowing LAPTM5 translocation from the Golgi to the lysosome with the aid of GGA3.	SIGNOR-278768
Q9P0N8	P13569	1	ubiquitination	down-regulates quantity by destabilization	0.2	A catalytically dead MARCH2 RING mutant was unable to promote CFTR degradation.\|In vivo ubiquitination assays demonstrated the ubiquitination of CFTR by MARCH2, and overexpression of MARCH2, like that of CAL and STX6, led to a dose dependent degradation of mature CFTR that was blocked by bafilomycin A1 treatment.	SIGNOR-278584
P53355	Q86YT6	0	polyubiquitination	down-regulates quantity by destabilization	0.437	Transient expression of DIP-1 in HeLa cells antagonizes the anti-apoptotic function of DAPK to promote a caspase-dependent apoptosis. These studies also demonstrate that DAPK is an in vitro and in vivo target for ubiquitination by DIP-1, thereby providing a mechanism by which DAPK activities can be regulated through proteasomal degradation.	SIGNOR-272602
P53350	Q99661	1	phosphorylation	up-regulates activity	0.812	Active PLK1, in turn, phosphorylates MCAK at Ser715 which promotes its microtubule depolymerase activity essential for faithful chromosome segregation.	SIGNOR-276931
Q03135	P12931	0	phosphorylation	down-regulates activity	0.764	Caveolin-1 is phosphorylated on tyr(14) in response to both oxidative and hyperosmotic stress. In the present paper, we show that this phosphorylation requires activation of the src family kinase fyn	SIGNOR-118007
Q9H4B4	P30307	1	phosphorylation	up-regulates	0.731	Cdc25c phosphorylation on serine 191 by plk3 promotes its nuclear translocation	SIGNOR-122090
P14635	P30304	0	dephosphorylation	up-regulates activity	0.855	Cdc25A dephosphorylates and activates CyclinE\u2013Cdk2, CyclinA\u2013Cdk2 and CyclinB\u2013Cdk1, whereas Cdc25B and Cdc25C primarily target CyclinB\u2013Cdk1 [4,5] .	SIGNOR-277137
Q07889	P01112	1	guanine nucleotide exchange factor	up-regulates activity	0.892	The enhancement of H-Ras GTP levels induced by oncogenic K-Ras was abrogated when the expression of endogenous Sos was suppressed, implicating Sos as an essential intermediate in the cross talk between oncogenic K-Ras and WT H-Ras.	SIGNOR-59472
Q9Y4C1	P84243	1	demethylation	up-regulates activity	0.2	Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9.	SIGNOR-276845
P55268	P31276	0	transcriptional regulation	up-regulates quantity by expression	0.2	The specificity of binding of these two proteins to the Lamin B2 origin is confirmed by both band-shift and in vitro footprinting assays. In addition, the ability of HOXC10 and HOXC13 to increase the activity of a promoter containing the 74 bp sequence, as assayed by CAT-assay experiments, demonstrates a direct interaction of these homeoproteins with the origin sequence in mammalian cells.	SIGNOR-261644
Q9UM73	Q92529	1	phosphorylation	up-regulates	0.44	Anaplastic lymphoma kinase (alk), which turned out to be one of these phosphoproteins, was constitutively activated and associated with the ptb domain of shcc in three neuroblastoma cells. In vitro kinase assay revealed that shcc is a potent substrate of the activated alk kinase. The alk gene locus was significantly amplified in both of these cell lines, suggesting that gene amplification leads to constitutive activation of the alk kinase, which results in hyperphosphorylation of shcc.	SIGNOR-91537
P53350	Q9NYQ6	1	phosphorylation	down-regulates activity	0.2	In contrast to the non autonomous polarity defects caused by transgenic expression of Celsr1 LLtoAA, Plk1 inhibition did not cause a significant alteration in Celsr1 interphase polarity (XREF_FIG).\|Plk1 phosphorylates the Celsr1 cytoplasmic domain in\nvitro .	SIGNOR-279094
Q9NR28	Q07812	0	relocalization	up-regulates	0.545	Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi	SIGNOR-87109
O75874	P36956	0	transcriptional regulation	up-regulates quantity by expression	0.282	IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells\|evidence that IDH1 may regulate lipogenesis in hepatic cells	SIGNOR-253132
P31749	P26358	1	phosphorylation	up-regulates	0.527	Akt1 kinase colocalizes and directly interacts with dnmt1 and phosphorylates ser143. Phosphorylated dnmt1 peaks during dna synthesis, before dnmt1 methylation. Depletion of akt1 or overexpression of dominant-negative akt1 increases methylated dnmt1, resulting in a decrease in dnmt1 abundance. In mammalian cells, phosphorylated dnmt1 is more stable than methylated dnmt1.	SIGNOR-170530
P01210	Q9H1B7	0	transcriptional regulation	down-regulates quantity by repression	0.307	EAP1 encoded a nuclear protein expressed in neurons involved in the inhibitory and facilitatory control of reproduction. EAP1 transactivated genes required for reproductive function, such as GNRH1, and repressed inhibitory genes, such as preproenkephalin. It contained a RING finger domain of the C3HC4 subclass required for this dual transcriptional activity.These results suggest that EAP1 is a transcriptional regulator that, acting within the neuroendocrine brain, contributes to controlling female reproductive function.	SIGNOR-267155
P06493	P49450	1	phosphorylation	down-regulates quantity by destabilization	0.68	Here, we report that the phosphorylation of CENP-A Ser68 primes the ubiquitin-proteasome-mediated proteolysis of CENP-A during mitotic phase in human cultured cells.the mitotic CENP-A degradation specifically depends on Cdk1 activity.	SIGNOR-277576
Q06124	Q14511	1	dephosphorylation	down-regulates activity	0.488	In this study we demonstrated that SHP-2 inhibits tyrosine phosphorylation of Cas-L, and negatively regulates the cell migration induced by Cas-L.\|These results show that both SH2 domains of SHP-2 are necessary for the interaction with Cas-L.\nIn this study we demonstrated that SHP-2 inhibits tyrosine phosphorylation of Cas-L, and negatively regulates the cell migration induced by Cas-L. Furthermore, our data raise the possibility that Cas-L is a direct substrate for SHP-2, although SHP-2 may inhibit Cas-L phosphorylation indirectly by regulating kinase activity.	SIGNOR-277083
Q01196	P28482	0	phosphorylation	up-regulates activity	0.2	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. The presence of these mutations results in an increase in the amount of ubiquitinated AML1c in the matrix, and increases the half-life of this insoluble AML1c. One possible model to explain these observations is that phosphorylation might be necessary for the normal process of both proteasome degradation and transcriptional activation.	SIGNOR-138973
P46937	Q15831	0	phosphorylation	down-regulates activity	0.305	LKB1 induces phosphorylation of Yap, leading to Yap nuclear exclusion and ultimately its degradation.\|These data indicated that LKB1 expression inhibits Yes-associated protein transcriptional function.	SIGNOR-280139
Q92879	P11802	0	phosphorylation	up-regulates activity	0.398	These studies showed that both the increased levels of CUGBP1 and cdk4-mediated hyper-phosphorylation of CUGBP1 are involved in the age-associated induction of the CUGBP1-eIF2 complex. The CUGBP1-eIF2 complex is bound to C/EBPbeta mRNA in the liver of old animals, and this binding correlates with the increased amounts of liver-enriched activator protein and liver-enriched inhibitory protein.	SIGNOR-262735
Q9NTX7	O15169	1	ubiquitination	down-regulates quantity by destabilization	0.645	Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.	SIGNOR-263335
P84243	Q15652	0	demethylation	down-regulates activity	0.2	We now determine that JMJD1C is recruited by USF-1 to various lipogenic genes for H3K9 demethylation to enhance chromatin accessibility in the fed state.	SIGNOR-265169
P48764	Q13237	0	phosphorylation	down-regulates activity	0.377	CGMP and cGKII increased NHE3 phosphorylation at three sites (rabbit Ser (554), Ser (607), and Ser (663), equivalent to mouse Ser (552), Ser (605), and Ser (659)), all of which had to be present at the same time for cGMP to inhibit NHE3.\|cGMP and cGKII rapidly inhibited NHE3, which was associated with reduced surface NHE3.	SIGNOR-280096
P68400	Q96PX8	1	phosphorylation	up-regulates activity	0.2	In our studies, SICD was phosphorylated by PKA, PKC, and CK2, and association of SLITRK1 with 14-3-3 was regulated by phosphorylation at Ser695. Co-precipitation experiments demonstrated much greater recovery of 14-3-3 in SLITRK1 precipitates when wild-type or S695E was used, as compared with S695A, consistent with the results with purified peptides.	SIGNOR-273633
P04083	P24723	0	phosphorylation	up-regulates	0.2	The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].The phosphorylation of serine 27 is essential for annexin a1 membrane localization.	SIGNOR-202792
P01112	Q9Y397	0	palmitoylation	up-regulates activity	0.435	Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.	SIGNOR-261352
Q13085	Q8NHY2	0	ubiquitination	down-regulates quantity by destabilization	0.2	TRB3 appears to inhibit ACC activity by functioning as an adaptor for COP1. Taken together, these results suggest that TRB3 may promote loss of fat by mediating the COP1-dependent ubiquitination and inactivation of ACC. Taking these results together, we propose that TRB3 may protect against diet-induced obesity by stimulating fatty acid oxidation in adipose during fasting through the COP1-mediated ubiquitination and degradation of ACC (Fig. 4D).	SIGNOR-271598
P68366	Q8NG68	0	tyrosination	down-regulates	0.286	Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization	SIGNOR-176927
P52732	Q8TDX7	0	phosphorylation	up-regulates activity	0.407	NEK7 regulates these processes in part through phosphorylation of the kinesin Eg5/KIF11, promoting its accumulation on microtubules in distal dendrites.	SIGNOR-273890
P52564	O15264	1	phosphorylation	up-regulates activity	0.661	p38-δ is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7. we investigated whether this Thr180-Gly-Tyr182 motif was essential for p38-δ activation. Taken together, these results suggest that the dual phosphorylation TGY motif is required for p38-δ activation.	SIGNOR-273952
Q9UKV5	P04035	1	ubiquitination	down-regulates quantity by destabilization	0.492	Gp78 mediates the sterol regulated ubiquitination of HMGCR.	SIGNOR-278622
Q6UUV9	Q13131	0	phosphorylation	down-regulates	0.285	Here we show that both ampk and calcineurin modulate longevity exclusively through post-translational modification of crtc-1, the sole c. elegans crtc. We demonstrate that crtc-1 is a direct ampk target.	SIGNOR-172136
Q9BSI4	P08047	0	transcriptional regulation	up-regulates quantity by expression	0.2	Transfection of a plasmid carrying the Sp1 transcription factor into Sp-deficient SL2 cells strongly activated TIN2 promoter-driven luciferase reporter expression.	SIGNOR-271698
Q9P2F6	P61586	1	gtpase-activating protein	down-regulates activity	0.709	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-260472
P98066	P17676	0	transcriptional regulation	up-regulates quantity by expression	0.302	In cotransfection experiments, the C/EBP beta protein trans-activated 10-15-fold the cAspAT gene promoter in HepG2 cells.	SIGNOR-254055
Q9UNE7	Q99717	1	ubiquitination	down-regulates	0.343	In ad-dition, some proteins (e.g. Chip, carboxyl terminus of hsc70-interacting protein) inhibit the signaling activi-ties of smad1/5 by recruiting smad1/5 from the functional r-/co-smad complex and further pro-moting the ubiquitination and degradation of smad1/5 in a chaperone-independent manne	SIGNOR-195690
P67775	Q8NEL9	1	dephosphorylation	up-regulates activity	0.2	Here we incubated a recombinant preparation of the phospholipase in vitro with several enzymes including protein kinase CK2 (CK2), extracellular signal-regulated kinase 2 (ERK2), and protein phosphatase 2A (PP2A) to identify effects that might be of regulatory importance in vivo.Major findings were that 1) CK2 phosphorylated the phospholipase on serines 93, 105, and 716; 2) ERK2 phosphorylated the enzyme on serine 730; 3) there was cross-antagonism between the reactions that phosphorylated serines 716 and 730; 4) PP2A selectively hydrolyzed phosphate groups that were esterified to serines 716 and 730. The results of two independent experiments with each type of assay indicated that the incubation caused a 50% loss of phospholipase activity (TableV). These results differed from those of corresponding incubation experiments with PA-PLA1α plus ERK2 and MgATP (see “Experimental Procedures”), which provided no evidence for complex formation or phosphorylation-dependent loss of phospholipase activity	SIGNOR-262975
P23771	Q15797	0	transcriptional regulation	up-regulates quantity	0.291	Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation	SIGNOR-268938
P27361	P50616	1	phosphorylation	down-regulates	0.352	Biochemical analyses have then shown that erk mapk (erk2) and jnk/sapk (jnk2) bind to and phosphorylate tob in vitro. Erk catalyzes the phosphorylation more efficiently than jnk	SIGNOR-88728
Q9Y618	Q13555	0	phosphorylation	down-regulates	0.2	The kinase activity of camkii was essential for the activation of notch signaling. We also determined that camkii could enhance the association between notch1-ic and rbp-jk. Furthermore, the physical association between rbp-jk and smrt was substantially suppressed by camkii. We demonstrated that camkii directly bound and phosphorylated smrt at ser-1407, thereby facilitating smrt translocation from the nucleus to the cytoplasm and proteasome-dependent degradation.	SIGNOR-191777
P41182	P27361	0	phosphorylation	down-regulates	0.405	Here we show that antigen receptor activation leads to bcl-6 phosphorylation by mitogen-activated protein kinase (mapk). Phosphorylation, in turn, targets bcl-6 for rapid degradation by the ubiquitin/proteasome pathway.	SIGNOR-58493
P36896	P84022	1	phosphorylation	up-regulates activity	0.741	ActRIIB, and then partners with a type I receptor, either activin receptor-like kinase 4 (ALK4 or ActRIB) or ALK5 (T²RI), to induce phosphorylation of Smad2/Smad3 and activate a TGF-²-like signaling pathway	SIGNOR-235160
O00141	P28482	1	phosphorylation	up-regulates activity	0.309	SGK1 was found to physically interact with ERK1/2 as well as MEK1/2. Furthermore, SGK1 mediated the phosphorylation of ERK2 on Ser(29) in a serum-dependent manner. Replacement of Ser(29) to aspartic acid, which mimics the phosphorylation of Ser(29), enhanced the ERK2 activity as well as the MEK/ERK complexes formation.	SIGNOR-276223
Q9H0A0	P04637	1	acetylation	up-regulates quantity by stabilization	0.337	NAT10 acetylates p53 at K120 and stabilizes p53 by counteracting Mdm2 action. In addition, NAT10 promotes Mdm2 degradation with its intrinsic E3 ligase activity.	SIGNOR-272406
P84243	Q9NRC8	0	deacetylation	up-regulates activity	0.2	SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation.\|Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression.	SIGNOR-275872
Q92974	P27448	0	phosphorylation	up-regulates activity	0.382	Rho-Rac guanine nucleotide exchange factor 2 (ARHGEF2), which activates Ras homolog family member A (RHOA), is anchored to the microtubule network and sequestered in an inhibited state through binding to dynein light chain Tctex-1 type 1 (DYNLT1). We showed in mammalian cells that liver kinase B1 (LKB1) activated the microtubule affinity-regulating kinase 3 (MARK3), which in turn phosphorylated ARHGEF2 at Ser151 This modification disrupted the interaction between ARHGEF2 and DYNLT1 by generating a 14-3-3 binding site in ARHGEF2, thus causing ARHGEF2 to dissociate from microtubules.	SIGNOR-277368
P38435	P00740	1	carboxylation	up-regulates activity	0.683	The direct gamma-carboxyglutamic acid analysis and the N-terminal sequence analysis of the myotube-synthesized F.IX demonstrate efficient carboxylation at 11 of 12 γ-carboxyglutamic acid residues. \|In previous work54 we have demonstrated that the γ-glutamyl carboxylase is present in skeletal muscle, but at a level only 5% to 10% of that found in the liver. This level of enzyme appears to be sufficient to provide full carboxylation of F.IX synthesized in myotubes\|Glu 7, 8, 15, 17, 20, 21, 26, 27, 30, 33, and 36 are each less than 10% of the yield at the previous and subsequent cycles. Only a single γ-carboxylated residue, Gla 40, was not assessed by N-terminal sequencing.	SIGNOR-263687
P30291	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.329	Serine 211 phosphorylation occurred under control conditions in the absence of CK1δ and in the presence of GSK3-β (Fig. 5, D and E).	SIGNOR-276632
P49841	Q8IZQ8	1	phosphorylation	down-regulates activity	0.397	In vitro and in vivo (HEK 293 cells) kinase assays with synthetic peptides and full-length myocardin demonstrated that myocardin was a primed GSK3beta substrate, with serines 455 to 467 and 624 to 636 being the major GSK3beta phosphorylation sites. GSK3β phosphorylation at the sites identified inhibits myocardin intrinsic transcriptional activity	SIGNOR-251247
Q9H4A3	P31749	0	phosphorylation	up-regulates	0.393	Phosphorylation of wnk1 on thr-58 contributes to sgk1 activation. these data suggest that activation of sgk1 by wnk1 requires the catalytic activity of akt.	SIGNOR-252481
P68400	P35222	1	phosphorylation	up-regulates activity	0.556	The major CK2 phosphorylation site in this domain is Thr393, a solvent-accessible residue in a key hinge region of the molecule. Mutation of this single amino acid reduces beta-catenin phosphorylation, cotranscriptional activity, and stability.	SIGNOR-250849
P59595	P63279	0	sumoylation	up-regulates activity	0.2	In this study, we identified Ubc9 as a host protein that interacts specifically with SARS-CoV N protein. This interaction was verified both in vivo and in vitro. Furthermore, we showed that, in addition to phosphorylation, the N protein was modified by covalent attachment of SUMO to its lysine 62 residue. Evidence provided demonstrated that sumoylation may promote homo-oligomerization of the protein.	SIGNOR-260263
O00267	P50750	0	phosphorylation	up-regulates	0.776	We describe an evolutionarily conserved repetitive heptapeptide motif (consensus = g-s-r/q-t-p) in the c-terminal region (ctr) of hspt5, which, like the c-terminal domain (ctd) of rna pol ii, is highly phosphorylated by p-tefb. Thr-4 residues of the ctr repeats are functionally important phosphorylation sites. In vitro, thr-4 phosphorylation is critical for the elongation activation activity of dsif	SIGNOR-143939
Q99990	P51812	0	phosphorylation	down-regulates activity	0.2	Site-directed mutagenesis and immunoprecipitation experiments revealed that RSK2 phosphorylated VGLL1 at S84 in the presence of TGF-β. Mutation of VGLL1 at S84 suppressed VGLL1-TEAD4 binding and the subsequent transcriptional activation of matrix metalloprotease 9 (MMP9).	SIGNOR-273842
Q9ULU4	Q8IVL1	1	transcriptional regulation	up-regulates quantity by expression	0.2	We also confirmed transcriptional coactivator functions of ZMYND8 in ERα-driven reporter assays and on endogenous E2-dependent genes (Figure 5F,G). siRNA knockdown of ZMYND8 showed markedly decreased transcription at the presumptive ERα/Z3 target genes ADORA1 and NAV2, while the classical ERα targets pS2/TFF1 and GREB1 appear to be less affected (Figure 5G), suggesting likely gene-specificity of ZMYND8.	SIGNOR-266209
O95835	P17612	0	phosphorylation	up-regulates	0.2	Here, we show that cyclic amp (camp)-dependent protein kinase (pka) phosphorylates lats and thereby enhances its activity sufficiently to phosphorylate yap on ser381.	SIGNOR-236991
P08254	Q9UGU0	0	transcriptional regulation	up-regulates quantity by expression	0.416	This result indicates that expression of SPBP is sufficient to transactivate a minimal promoter containing a single copy of the SPRE, as well as the full-length stromelysin promoter.	SIGNOR-266223
P04637	O14965	0	phosphorylation	up-regulates activity	0.778	The N-terminus of E2F1 can interact directly with a region towards the C-terminus of p53, resulting in increased nuclear retention of p53 and p53-mediated transcription and apoptosis. This is inhibited by competition between p53 and cyclin A at the binding site within E2F19,10. The interaction between p53 and E2F1 is enhanced by phosphorylation of p53 on Ser315, a residue within the E2F1 binding region that is phosphorylated by cell cycle kinases such as cdk1, cdk2, cdk9 and Aurora kinase A	SIGNOR-120836
Q12857	Q13562	1	transcriptional regulation	up-regulates quantity	0.284	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268890
P11831	P68400	0	phosphorylation	up-regulates activity	0.552	Casein kinase II (CKII) phosphorylates the mammalian transcription factor serum response factor (SRF) on a serine residue(s) located within a region of the protein spanning amino acids 70 to 92, thereby enhancing its DNA-binding activity in vitro.\| Nevertheless, additional mutation of serines 77 and 79 was required before phosphorylation and enhanced binding were completely abolished. Thus, serines 77 and 79 could also be recognized by CKII if serines 83 and 85 were mutated.	SIGNOR-250955
Q13131	Q9NR19	1	phosphorylation	up-regulates activity	0.275	This translocation is mediated by AMP-activated protein kinase (AMPK)-dependent ACSS2 Ser659 phosphorylation and subsequent exposure of the nuclear localization signal of ACSS2 to KPNA1/importin α5 for binding. In the nucleus, ACSS2 forms a complex with TFEB (transcription factor EB) and utilizes the acetate generated from histone deacetylation to locally produce acetyl-CoA for histone acetylation in the promoter regions of TFEB target genes.	SIGNOR-271822
Q86Y07	O75531	1	phosphorylation	down-regulates	0.502	We demonstrate that phosphorylation of ser4 and/or thr2/thr3 abrogates the interaction of baf with dna and reduces its interaction with the lem domain. Coexpression of vrk1 and gfp-baf greatly diminishes the association of baf with the nuclear chromatin/matrix and leads to its dispersal throughout the cell	SIGNOR-143368
P63162	O15355	0	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
P40763	P45984	0	phosphorylation	up-regulates	0.482	Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.	SIGNOR-179275
P35372	P02775	0	chemical inhibition	down-regulates activity	0.385	Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors.	SIGNOR-258413
Q15418	P01100	1	phosphorylation	up-regulates activity	0.529	We now provide evidence that two growth-regulated, nucleus- and cytoplasm-localized protein kinases, 90-kda ribosomal s6 kinase (rsk) and mitogen-activated protein kinase (map kinase), contribute to the serum-induced phosphorylation of c-fos. The major phosphopeptides derived from biosynthetically labeled c-fos correspond to phosphopeptides generated after phosphorylation of c-fos in vitro with both rsk and map kinase. The phosphorylation sites identified for rsk (ser-362) and map kinase (ser-374) are in the transrepression domain. Cooperative phosphorylation at these sites by both enzymes was observed in vitro and reflected in vivo by the predominance of the peptide phosphorylated on both sites, as opposed to singly phosphorylated peptides. This study suggests a role for nuclear rsk and map kinase in modulating newly synthesized c-fos phosphorylation and downstream signaling.	SIGNOR-37154
P18850	Q16539	0	phosphorylation	up-regulates activity	0.585	This observation not only confirms the specific role for IFN-γ-induced p38 MAPK-dependent phosphorylation of ATF6 at the T166 site but also indicates a connection between phosphorylation and proteolytic activation.	SIGNOR-276841

Q9HBH9

P28482

0

phosphorylation

up-regulates

0.6

We have identified a new subfamily of murine serine/threonine kinases, whose members, map kinase-interacting kinase 1 (mnk1) and mnk2, bind tightly to the growth factor-regulated map kinases, erk1 and erk2erk and p38 phosphorylate mnk1 and mnk2, which stimulates their in vitro kinase activity

SIGNOR-48338

Q9UHD2

P42345

1

phosphorylation

up-regulates activity

0.42

They later demonstrated that TANK-binding kinase 1 (TBK1) interacts with and phosphorylates mTOR on Ser 2159, to promote catalytic activity of mTOR [216].

SIGNOR-278237

P35637

Q99873

0

methylation

down-regulates activity

0.485

PRMT1 catalyzes the arginine methylation of Fused in Sarcoma (FUS), an RNA-binding protein that interacts with RALY. We demonstrate that RALY down-regulation decreases protein arginine N-methyltransferase 1 levels, thus reducing FUS methylation. It is known that mutations in the FUS nuclear localization signal (NLS) retain the protein to the cytosol, promote aggregate formation, and are associated with amyotrophic lateral sclerosis.

SIGNOR-262274

Q16539

P35638

1

phosphorylation

up-regulates activity

0.61

CHOP, a member of the C/EBP family of transcription factors, mediates effects of cellular stress on growth and differentiation. It accumulates under conditions of stress and undergoes inducible phosphorylation on two adjacent serine residues (78 and 81). In vitro, CHOP is phosphorylated on these residues by p38 mitogen-activated protein kinase (MAP kinase).

SIGNOR-250096

P35968

Q05397

1

null

up-regulates activity

0.496

Here we show that genetic or pharmacological FAK inhibition in ECs prevents VEGF-stimulated permeability downstream of VEGF receptor or Src tyrosine kinase activation in vivo. VEGF promotes tension-independent FAK activation

SIGNOR-261945

O95551

P36896

0

phosphorylation

up-regulates activity

0.28

ALK4 phosphorylated TTRAP in vitro (Fig. 6A). The band migrating at the position of TTRAP was excised and analyzed by LC-MS/MS. One TTRAP peptide was phosphorylated either on T88 and T92, or on T92 only (Fig. 6B).We tested in vivo phosphorylation of Strep-TTRAP by co-expression with mouse Alk4 in HEK293T cells, and affinity-purified TTRAP. In this preparation TTRAP-specific peptides were reproducibly found in both the singly (T92) and doubly phosphorylated form (T88/T92). mutant TTRAPT88A,T92A is not able to rescue the TtrapMO phenotype, suggesting that phosphorylation of Ttrap on Thr88 and Thr92 is essential for Ttrap function.

SIGNOR-262612

P06241

O75553

1

phosphorylation

down-regulates activity

0.614

Tyrosine phosphorylation of Dab1 by Fyn inhibits its interaction with APP, while increasing its interaction with Fyn.

SIGNOR-278476

P25963

Q12923

0

dephosphorylation

up-regulates quantity by stabilization

0.442

Identification of IkappaBalpha as a substrate of Fas-associated phosphatase-1|A full-length FAP-1 protein preferentially dephosphorylates Tyr-42 of IkBa|Moreover, other studies have shown that tyrosine phosphorylation of IkBa on Tyr-42 (which occurs with Fas ligand binging) protected against inducible degradation both in vitro [30] and in vivo [38]

SIGNOR-248712

Q13233

O14920

1

phosphorylation

up-regulates activity

0.595

These results suggested that IKK\u03b2 was a likely substrate for MEKK1 and that MEKK1 phosphorylation of IKK\u03b2 increased its kinase activity.

SIGNOR-279339

Q14653

Q9BZ95

0

methylation

up-regulates activity

0.2

We found that lysine methyltransferase NSD3 interacts with and directly monomethylates IRF3 in the nucleus, leading to the enhanced IRF3 transcriptional activity and antiviral immune responses.

SIGNOR-259198

Q12913

P06213

1

dephosphorylation

down-regulates

0.304

Dephosphorylation of autophosphorylated insulin and epidermal-growth-factor receptors by two major subtypes of protein-tyrosine-phosphatase from human placenta.

SIGNOR-21295

P43405

Q13422

1

phosphorylation

up-regulates

0.404

Syk phoshorylatesikarosat unique c-terminal serine phosphorylation sites s358 and s361, thereby augmenting its nuclear localization and sequence-specific dna binding activity. Mechanistically, we establish that syk-inducedikarosactivation is essential for its nuclear localization and optimal transcription factor function.

SIGNOR-199100

Q13153

Q8IYU2

1

phosphorylation

down-regulates activity

0.2

Using a proteomic approach, we identified serine 385 as a target of group-I PAK kinases […] We have established in vitro that HACE1 is a direct target of PAK1 kinase activity.

SIGNOR-255537

Q13153

Q13352

1

phosphorylation

up-regulates

0.2

Serine 28 phosphorylation of nrif3 confers its co-activator function for estrogen receptor-alpha transactivation. p21-activated protein kinase 1 (pak1) phosphorylates eralpha at ser305 and this modification is important in eralpha transactivation function.

SIGNOR-178795

Q9Y4K3

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.466

CHIP promotes TRAF6 ubiquitination and degradation.|These results suggest that CHIP negatively regulates the stability of TRAF6.

SIGNOR-278670

P03956

P02458

1

cleavage

down-regulates quantity by destabilization

0.445

MMP-1 cleaves type II collagen at the peptide bond Gly906-Leu907 Proteolysis of triple-helical collagen is an important step in the progression toward irreversible tissue damage in osteoarthritis. Earlier work on the expression of enzymes in cartilage suggested that collagenase-1 (MMP-1) contributes to the process.

SIGNOR-256341

Q00987

P61254

1

ubiquitination

down-regulates quantity by destabilization

0.498

In addition, Mdm2 ubiquitylates L26, leading to its proteasome-mediated degradation.|We now report that Mdm2 regulates p53 levels also by targeting ribosomal protein L26.

SIGNOR-278828

P59595

P35354

1

transcriptional regulation

up-regulates activity

0.2

SARS-CoV N protein activates COX-2 promoter and induces COX-2 protein expression

SIGNOR-262314

P41181

Q07002

0

phosphorylation

down-regulates quantity by destabilization

0.26

CDK18 controls AQP2 through phosphorylation at serine 261 and STUB1-mediated ubiquitination. |We had previously observed that a decrease in the phosphorylation of AQP2 at S261 is associated with a decrease in its poly-ubiquitination and an increase in its abundance

SIGNOR-264562

P12931

Q99835

0

phosphorylation

up-regulates

0.436

Instead, shh rapidly and locally stimulated phosphorylation of the src family kinase (sfk) members src and fyn in a smo-dependent fashion.

SIGNOR-178610

P49137

Q14134

1

phosphorylation

up-regulates activity

0.307

ATDC was phosphorylated directly by MAPKAP kinase 2 (MK2) at Ser550 in an ATM-dependent manner. Phosphorylation at Ser-550 by MK2 was required for the radioprotective function of ATDC.

SIGNOR-273675

P06239

P43403

1

phosphorylation

up-regulates activity

0.619

We show that ZAP-70 has a primary autophosphorylation site at Tyr-292, with a secondary site at Tyr-126. We also show additional phosphorylation at Tyr-69, Tyr-178, Tyr-492, and Tyr-493 upon the addition of the protein tyrosine kinase, p56lck

SIGNOR-249375

P51955

Q76N32

1

phosphorylation

down-regulates quantity by destabilization

0.251

In this study we show phosphorylation of Cep68 by Nek2 creates a potential phosphodegron that directs Cep68 destruction through the activity of SCF-beta-Trcp.|Our above results showed that Nek2 promoted mitotic degradation of Cep68.

SIGNOR-279471

Q9UHH9

P68400

0

phosphorylation

down-regulates quantity by destabilization

0.255

CK2 physiologically phosphorylates IP6K2 at amino acid residues S347 and S356 contained within a PEST sequence, a consensus site for ubiquitination. HCT116 cells depleted of IP6K2 are resistant to cell death elicited by CK2 inhibitors. CK2 phosphorylation at the degradation motif of IP6K2 enhances its ubiquitination and subsequent degradation.

SIGNOR-273625

Q9NW38

P35222

1

ubiquitination

up-regulates activity

0.2

Here we provide evidence that FANCL increases the activity and expression of beta-catenin, a key pluripotency factor in hematopoietic stem cells.|We show that FANCL ubiquitinates \u03b2-catenin with atypical ubiquitin chain extension known to have nonproteolytic functions.

SIGNOR-278651

P54132

P33981

0

phosphorylation

up-regulates activity

0.315

Moreover, in mitosis, TTK promotes phosphorylation of Bloom syndrome protein (BLM) and subsequent interaction of BLM with PLK1, ensuring accurate chromosome segregation xref .|Moreover, in mitosis, TTK promotes phosphorylation of Bloom syndrome protein and subsequent interaction of Bloom syndrome protein with PLK1, ensuring accurate chromosome segregation .

SIGNOR-280156

P16284

P07332

0

phosphorylation

up-regulates activity

0.276

PECAM-1 Is Phosphorylated by Fer and, To a Lesser Extent, by Fes. These results suggest that Fer not only functions as a tyrosine kinase for PECAM-1 but also that Fer modulates the downstream signaling of PECAM-1 by inducing phosphorylation of SHP-2 and Gab1.

SIGNOR-262868

P17612

Q7Z2W7

1

phosphorylation

up-regulates activity

0.2

Using specific pharmacological and molecular tools combined with patch-clamp current recordings, we found that in heterologously expressed HEK-293 (human embryonic kidney) cells, TRPM8 channel is inhibited by the G(i) protein/adenylate cyclase (AC)/cAMP/protein kinase A (PKA) signaling cascade. We further identified the TRPM8 S9 and T17 as two key PKA phosphorylation sites regulating TRPM8 channel activity. the intracellular serine/threonine protein phosphatase 2A (PP2A) dephosphorylates TRPM8 Ser-9 and Thr-17 inhibiting the channel activity.

SIGNOR-273791

Q13153

P52565

1

phosphorylation

down-regulates

0.611

Pak1 binds and phosphorylates rhogdi both in vitro and in vivo at ser101 and ser174. This resulted in dissociation of rac1-rhogdi, but not rhoa-rhogdi, complexes, as determined by in vitro assays of complexation and in vivo by coimmunoprecipitation analysis. We observed that cdc42-induced rac1 activation is inhibited by expression of pak1 autoinhibitory domain. The dissociation of rac1 from rhogdi and its subsequent activation stimulated by pdgf or egf is also attenuated by pak1 autoinhibitory domain, and this is dependent on the ability of rhogdi to be phosphorylated at ser101/174.

SIGNOR-126654

Q96GX5

P56211

1

phosphorylation

up-regulates activity

0.73

We identified cyclic adenosine monophosphateregulated phosphoprotein 19 (Arpp19) and -Endosulfine as two substrates of Gwl that, when phosphorylated by this kinase, associate with and inhibit PP2A, thus promoting mitotic entry.

SIGNOR-243611

Q12778

Q13627

0

phosphorylation

down-regulates

0.506

Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity.

SIGNOR-183670

Q14774

P14635

1

transcriptional regulation

up-regulates quantity by expression

0.2

In this study, we have identified cell cycle regulatory genes as downstream targets of the homeobox gene HLX in cultured trophoblast cells, namely RB1, MYC, EGR1, CDKN1C, ELK1, CCNB1, and JUN. RB1 and MYC mRNA expression was increased with HLX inactivation, whereas EGR1, CDKN1C, ELK1, CCNB1, and JUN mRNA expression was decreased compared with mock-transfected control cells.

SIGNOR-261619

P46934

Q13571

1

ubiquitination

up-regulates activity

0.476

These results suggest that LAPTM5 ubiquitination is mediated by Nedd4.|Thus, Nedd4 promotes the recruitment of GGA3 to LAPTM5, allowing LAPTM5 translocation from the Golgi to the lysosome with the aid of GGA3.

SIGNOR-278768

Q9P0N8

P13569

1

ubiquitination

down-regulates quantity by destabilization

0.2

A catalytically dead MARCH2 RING mutant was unable to promote CFTR degradation.|In vivo ubiquitination assays demonstrated the ubiquitination of CFTR by MARCH2, and overexpression of MARCH2, like that of CAL and STX6, led to a dose dependent degradation of mature CFTR that was blocked by bafilomycin A1 treatment.

SIGNOR-278584

P53355

Q86YT6

0

polyubiquitination

down-regulates quantity by destabilization

0.437

Transient expression of DIP-1 in HeLa cells antagonizes the anti-apoptotic function of DAPK to promote a caspase-dependent apoptosis. These studies also demonstrate that DAPK is an in vitro and in vivo target for ubiquitination by DIP-1, thereby providing a mechanism by which DAPK activities can be regulated through proteasomal degradation.

SIGNOR-272602

P53350

Q99661

1

phosphorylation

up-regulates activity

0.812

Active PLK1, in turn, phosphorylates MCAK at Ser715 which promotes its microtubule depolymerase activity essential for faithful chromosome segregation.

SIGNOR-276931

Q03135

P12931

0

phosphorylation

down-regulates activity

0.764

Caveolin-1 is phosphorylated on tyr(14) in response to both oxidative and hyperosmotic stress. In the present paper, we show that this phosphorylation requires activation of the src family kinase fyn

SIGNOR-118007

Q9H4B4

P30307

1

phosphorylation

up-regulates

0.731

Cdc25c phosphorylation on serine 191 by plk3 promotes its nuclear translocation

SIGNOR-122090

P14635

P30304

0

dephosphorylation

up-regulates activity

0.855

Cdc25A dephosphorylates and activates CyclinE\u2013Cdk2, CyclinA\u2013Cdk2 and CyclinB\u2013Cdk1, whereas Cdc25B and Cdc25C primarily target CyclinB\u2013Cdk1 [4,5] .

SIGNOR-277137

Q07889

P01112

1

guanine nucleotide exchange factor

up-regulates activity

0.892

The enhancement of H-Ras GTP levels induced by oncogenic K-Ras was abrogated when the expression of endogenous Sos was suppressed, implicating Sos as an essential intermediate in the cross talk between oncogenic K-Ras and WT H-Ras.

SIGNOR-59472

Q9Y4C1

P84243

1

demethylation

up-regulates activity

0.2

Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9.

SIGNOR-276845

P55268

P31276

0

transcriptional regulation

up-regulates quantity by expression

0.2

The specificity of binding of these two proteins to the Lamin B2 origin is confirmed by both band-shift and in vitro footprinting assays. In addition, the ability of HOXC10 and HOXC13 to increase the activity of a promoter containing the 74 bp sequence, as assayed by CAT-assay experiments, demonstrates a direct interaction of these homeoproteins with the origin sequence in mammalian cells.

SIGNOR-261644

Q9UM73

Q92529

1

phosphorylation

up-regulates

0.44

Anaplastic lymphoma kinase (alk), which turned out to be one of these phosphoproteins, was constitutively activated and associated with the ptb domain of shcc in three neuroblastoma cells. In vitro kinase assay revealed that shcc is a potent substrate of the activated alk kinase. The alk gene locus was significantly amplified in both of these cell lines, suggesting that gene amplification leads to constitutive activation of the alk kinase, which results in hyperphosphorylation of shcc.

SIGNOR-91537

P53350

Q9NYQ6

1

phosphorylation

down-regulates activity

0.2

In contrast to the non autonomous polarity defects caused by transgenic expression of Celsr1 LLtoAA, Plk1 inhibition did not cause a significant alteration in Celsr1 interphase polarity (XREF_FIG).|Plk1 phosphorylates the Celsr1 cytoplasmic domain in\nvitro .

SIGNOR-279094

Q9NR28

Q07812

0

relocalization

up-regulates

0.545

Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi

SIGNOR-87109

O75874

P36956

0

transcriptional regulation

up-regulates quantity by expression

0.282

IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells|evidence that IDH1 may regulate lipogenesis in hepatic cells

SIGNOR-253132

P31749

P26358

1

phosphorylation

up-regulates

0.527

Akt1 kinase colocalizes and directly interacts with dnmt1 and phosphorylates ser143. Phosphorylated dnmt1 peaks during dna synthesis, before dnmt1 methylation. Depletion of akt1 or overexpression of dominant-negative akt1 increases methylated dnmt1, resulting in a decrease in dnmt1 abundance. In mammalian cells, phosphorylated dnmt1 is more stable than methylated dnmt1.

SIGNOR-170530

P01210

Q9H1B7

0

transcriptional regulation

down-regulates quantity by repression

0.307

EAP1 encoded a nuclear protein expressed in neurons involved in the inhibitory and facilitatory control of reproduction. EAP1 transactivated genes required for reproductive function, such as GNRH1, and repressed inhibitory genes, such as preproenkephalin. It contained a RING finger domain of the C3HC4 subclass required for this dual transcriptional activity.These results suggest that EAP1 is a transcriptional regulator that, acting within the neuroendocrine brain, contributes to controlling female reproductive function.

SIGNOR-267155

P06493

P49450

1

phosphorylation

down-regulates quantity by destabilization

0.68

Here, we report that the phosphorylation of CENP-A Ser68 primes the ubiquitin-proteasome-mediated proteolysis of CENP-A during mitotic phase in human cultured cells.the mitotic CENP-A degradation specifically depends on Cdk1 activity.

SIGNOR-277576

Q06124

Q14511

1

dephosphorylation

down-regulates activity

0.488

In this study we demonstrated that SHP-2 inhibits tyrosine phosphorylation of Cas-L, and negatively regulates the cell migration induced by Cas-L.|These results show that both SH2 domains of SHP-2 are necessary for the interaction with Cas-L.\nIn this study we demonstrated that SHP-2 inhibits tyrosine phosphorylation of Cas-L, and negatively regulates the cell migration induced by Cas-L. Furthermore, our data raise the possibility that Cas-L is a direct substrate for SHP-2, although SHP-2 may inhibit Cas-L phosphorylation indirectly by regulating kinase activity.

SIGNOR-277083

Q01196

P28482

0

phosphorylation

up-regulates activity

0.2

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. The presence of these mutations results in an increase in the amount of ubiquitinated AML1c in the matrix, and increases the half-life of this insoluble AML1c. One possible model to explain these observations is that phosphorylation might be necessary for the normal process of both proteasome degradation and transcriptional activation.

SIGNOR-138973

P46937

Q15831

0

phosphorylation

down-regulates activity

0.305

LKB1 induces phosphorylation of Yap, leading to Yap nuclear exclusion and ultimately its degradation.|These data indicated that LKB1 expression inhibits Yes-associated protein transcriptional function.

SIGNOR-280139

Q92879

P11802

0

phosphorylation

up-regulates activity

0.398

These studies showed that both the increased levels of CUGBP1 and cdk4-mediated hyper-phosphorylation of CUGBP1 are involved in the age-associated induction of the CUGBP1-eIF2 complex. The CUGBP1-eIF2 complex is bound to C/EBPbeta mRNA in the liver of old animals, and this binding correlates with the increased amounts of liver-enriched activator protein and liver-enriched inhibitory protein.

SIGNOR-262735

Q9NTX7

O15169

1

ubiquitination

down-regulates quantity by destabilization

0.645

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

SIGNOR-263335

P84243

Q15652

0

demethylation

down-regulates activity

0.2

We now determine that JMJD1C is recruited by USF-1 to various lipogenic genes for H3K9 demethylation to enhance chromatin accessibility in the fed state.

SIGNOR-265169

P48764

Q13237

0

phosphorylation

down-regulates activity

0.377

CGMP and cGKII increased NHE3 phosphorylation at three sites (rabbit Ser (554), Ser (607), and Ser (663), equivalent to mouse Ser (552), Ser (605), and Ser (659)), all of which had to be present at the same time for cGMP to inhibit NHE3.|cGMP and cGKII rapidly inhibited NHE3, which was associated with reduced surface NHE3.

SIGNOR-280096

P68400

Q96PX8

1

phosphorylation

up-regulates activity

0.2

In our studies, SICD was phosphorylated by PKA, PKC, and CK2, and association of SLITRK1 with 14-3-3 was regulated by phosphorylation at Ser695. Co-precipitation experiments demonstrated much greater recovery of 14-3-3 in SLITRK1 precipitates when wild-type or S695E was used, as compared with S695A, consistent with the results with purified peptides.

SIGNOR-273633

P04083

P24723

0

phosphorylation

up-regulates

0.2

The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].The phosphorylation of serine 27 is essential for annexin a1 membrane localization.

SIGNOR-202792

P01112

Q9Y397

0

palmitoylation

up-regulates activity

0.435

Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.

SIGNOR-261352

Q13085

Q8NHY2

0

ubiquitination

down-regulates quantity by destabilization

0.2

TRB3 appears to inhibit ACC activity by functioning as an adaptor for COP1. Taken together, these results suggest that TRB3 may promote loss of fat by mediating the COP1-dependent ubiquitination and inactivation of ACC. Taking these results together, we propose that TRB3 may protect against diet-induced obesity by stimulating fatty acid oxidation in adipose during fasting through the COP1-mediated ubiquitination and degradation of ACC (Fig. 4D).

SIGNOR-271598

P68366

Q8NG68

0

tyrosination

down-regulates

0.286

Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization

SIGNOR-176927

P52732

Q8TDX7

0

phosphorylation

up-regulates activity

0.407

NEK7 regulates these processes in part through phosphorylation of the kinesin Eg5/KIF11, promoting its accumulation on microtubules in distal dendrites.

SIGNOR-273890

P52564

O15264

1

phosphorylation

up-regulates activity

0.661

p38-δ is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7. we investigated whether this Thr180-Gly-Tyr182 motif was essential for p38-δ activation. Taken together, these results suggest that the dual phosphorylation TGY motif is required for p38-δ activation.

SIGNOR-273952

Q9UKV5

P04035

1

ubiquitination

down-regulates quantity by destabilization

0.492

Gp78 mediates the sterol regulated ubiquitination of HMGCR.

SIGNOR-278622

Q6UUV9

Q13131

0

phosphorylation

down-regulates

0.285

Here we show that both ampk and calcineurin modulate longevity exclusively through post-translational modification of crtc-1, the sole c. elegans crtc. We demonstrate that crtc-1 is a direct ampk target.

SIGNOR-172136

Q9BSI4

P08047

0

transcriptional regulation

up-regulates quantity by expression

0.2

Transfection of a plasmid carrying the Sp1 transcription factor into Sp-deficient SL2 cells strongly activated TIN2 promoter-driven luciferase reporter expression.

SIGNOR-271698

Q9P2F6

P61586

1

gtpase-activating protein

down-regulates activity

0.709

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-260472

P98066

P17676

0

transcriptional regulation

up-regulates quantity by expression

0.302

In cotransfection experiments, the C/EBP beta protein trans-activated 10-15-fold the cAspAT gene promoter in HepG2 cells.

SIGNOR-254055

Q9UNE7

Q99717

1

ubiquitination

down-regulates

0.343

In ad-dition, some proteins (e.g. Chip, carboxyl terminus of hsc70-interacting protein) inhibit the signaling activi-ties of smad1/5 by recruiting smad1/5 from the functional r-/co-smad complex and further pro-moting the ubiquitination and degradation of smad1/5 in a chaperone-independent manne

SIGNOR-195690

P67775

Q8NEL9

1

dephosphorylation

up-regulates activity

0.2

Here we incubated a recombinant preparation of the phospholipase in vitro with several enzymes including protein kinase CK2 (CK2), extracellular signal-regulated kinase 2 (ERK2), and protein phosphatase 2A (PP2A) to identify effects that might be of regulatory importance in vivo.Major findings were that 1) CK2 phosphorylated the phospholipase on serines 93, 105, and 716; 2) ERK2 phosphorylated the enzyme on serine 730; 3) there was cross-antagonism between the reactions that phosphorylated serines 716 and 730; 4) PP2A selectively hydrolyzed phosphate groups that were esterified to serines 716 and 730. The results of two independent experiments with each type of assay indicated that the incubation caused a 50% loss of phospholipase activity (TableV). These results differed from those of corresponding incubation experiments with PA-PLA1α plus ERK2 and MgATP (see “Experimental Procedures”), which provided no evidence for complex formation or phosphorylation-dependent loss of phospholipase activity

SIGNOR-262975

P23771

Q15797

0

transcriptional regulation

up-regulates quantity

0.291

Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation

SIGNOR-268938

P27361

P50616

1

phosphorylation

down-regulates

0.352

Biochemical analyses have then shown that erk mapk (erk2) and jnk/sapk (jnk2) bind to and phosphorylate tob in vitro. Erk catalyzes the phosphorylation more efficiently than jnk

SIGNOR-88728

Q9Y618

Q13555

0

phosphorylation

down-regulates

0.2

The kinase activity of camkii was essential for the activation of notch signaling. We also determined that camkii could enhance the association between notch1-ic and rbp-jk. Furthermore, the physical association between rbp-jk and smrt was substantially suppressed by camkii. We demonstrated that camkii directly bound and phosphorylated smrt at ser-1407, thereby facilitating smrt translocation from the nucleus to the cytoplasm and proteasome-dependent degradation.

SIGNOR-191777

P41182

P27361

0

phosphorylation

down-regulates

0.405

Here we show that antigen receptor activation leads to bcl-6 phosphorylation by mitogen-activated protein kinase (mapk). Phosphorylation, in turn, targets bcl-6 for rapid degradation by the ubiquitin/proteasome pathway.

SIGNOR-58493

P36896

P84022

1

phosphorylation

up-regulates activity

0.741

ActRIIB, and then partners with a type I receptor, either activin receptor-like kinase 4 (ALK4 or ActRIB) or ALK5 (T²RI), to induce phosphorylation of Smad2/Smad3 and activate a TGF-²-like signaling pathway

SIGNOR-235160

O00141

P28482

1

phosphorylation

up-regulates activity

0.309

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

SIGNOR-276223

Q9H0A0

P04637

1

acetylation

up-regulates quantity by stabilization

0.337

NAT10 acetylates p53 at K120 and stabilizes p53 by counteracting Mdm2 action. In addition, NAT10 promotes Mdm2 degradation with its intrinsic E3 ligase activity.

SIGNOR-272406

P84243

Q9NRC8

0

deacetylation

up-regulates activity

0.2

SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation.|Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression.

SIGNOR-275872

Q92974

P27448

0

phosphorylation

up-regulates activity

0.382

Rho-Rac guanine nucleotide exchange factor 2 (ARHGEF2), which activates Ras homolog family member A (RHOA), is anchored to the microtubule network and sequestered in an inhibited state through binding to dynein light chain Tctex-1 type 1 (DYNLT1). We showed in mammalian cells that liver kinase B1 (LKB1) activated the microtubule affinity-regulating kinase 3 (MARK3), which in turn phosphorylated ARHGEF2 at Ser151 This modification disrupted the interaction between ARHGEF2 and DYNLT1 by generating a 14-3-3 binding site in ARHGEF2, thus causing ARHGEF2 to dissociate from microtubules.

SIGNOR-277368

P38435

P00740

1

carboxylation

up-regulates activity

0.683

The direct gamma-carboxyglutamic acid analysis and the N-terminal sequence analysis of the myotube-synthesized F.IX demonstrate efficient carboxylation at 11 of 12 γ-carboxyglutamic acid residues. |In previous work54 we have demonstrated that the γ-glutamyl carboxylase is present in skeletal muscle, but at a level only 5% to 10% of that found in the liver. This level of enzyme appears to be sufficient to provide full carboxylation of F.IX synthesized in myotubes|Glu 7, 8, 15, 17, 20, 21, 26, 27, 30, 33, and 36 are each less than 10% of the yield at the previous and subsequent cycles. Only a single γ-carboxylated residue, Gla 40, was not assessed by N-terminal sequencing.

SIGNOR-263687

P30291

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.329

Serine 211 phosphorylation occurred under control conditions in the absence of CK1δ and in the presence of GSK3-β (Fig. 5, D and E).

SIGNOR-276632

P49841

Q8IZQ8

1

phosphorylation

down-regulates activity

0.397

In vitro and in vivo (HEK 293 cells) kinase assays with synthetic peptides and full-length myocardin demonstrated that myocardin was a primed GSK3beta substrate, with serines 455 to 467 and 624 to 636 being the major GSK3beta phosphorylation sites. GSK3β phosphorylation at the sites identified inhibits myocardin intrinsic transcriptional activity

SIGNOR-251247

Q9H4A3

P31749

0

phosphorylation

up-regulates

0.393

Phosphorylation of wnk1 on thr-58 contributes to sgk1 activation. these data suggest that activation of sgk1 by wnk1 requires the catalytic activity of akt.

SIGNOR-252481

P68400

P35222

1

phosphorylation

up-regulates activity

0.556

The major CK2 phosphorylation site in this domain is Thr393, a solvent-accessible residue in a key hinge region of the molecule. Mutation of this single amino acid reduces beta-catenin phosphorylation, cotranscriptional activity, and stability.

SIGNOR-250849

P59595

P63279

0

sumoylation

up-regulates activity

0.2

In this study, we identified Ubc9 as a host protein that interacts specifically with SARS-CoV N protein. This interaction was verified both in vivo and in vitro. Furthermore, we showed that, in addition to phosphorylation, the N protein was modified by covalent attachment of SUMO to its lysine 62 residue. Evidence provided demonstrated that sumoylation may promote homo-oligomerization of the protein.

SIGNOR-260263

O00267

P50750

0

phosphorylation

up-regulates

0.776

We describe an evolutionarily conserved repetitive heptapeptide motif (consensus = g-s-r/q-t-p) in the c-terminal region (ctr) of hspt5, which, like the c-terminal domain (ctd) of rna pol ii, is highly phosphorylated by p-tefb. Thr-4 residues of the ctr repeats are functionally important phosphorylation sites. In vitro, thr-4 phosphorylation is critical for the elongation activation activity of dsif

SIGNOR-143939

Q99990

P51812

0

phosphorylation

down-regulates activity

0.2

Site-directed mutagenesis and immunoprecipitation experiments revealed that RSK2 phosphorylated VGLL1 at S84 in the presence of TGF-β. Mutation of VGLL1 at S84 suppressed VGLL1-TEAD4 binding and the subsequent transcriptional activation of matrix metalloprotease 9 (MMP9).

SIGNOR-273842

Q9ULU4

Q8IVL1

1

transcriptional regulation

up-regulates quantity by expression

0.2

We also confirmed transcriptional coactivator functions of ZMYND8 in ERα-driven reporter assays and on endogenous E2-dependent genes (Figure 5F,G). siRNA knockdown of ZMYND8 showed markedly decreased transcription at the presumptive ERα/Z3 target genes ADORA1 and NAV2, while the classical ERα targets pS2/TFF1 and GREB1 appear to be less affected (Figure 5G), suggesting likely gene-specificity of ZMYND8.

SIGNOR-266209

O95835

P17612

0

phosphorylation

up-regulates

0.2

Here, we show that cyclic amp (camp)-dependent protein kinase (pka) phosphorylates lats and thereby enhances its activity sufficiently to phosphorylate yap on ser381.

SIGNOR-236991

P08254

Q9UGU0

0

transcriptional regulation

up-regulates quantity by expression

0.416

This result indicates that expression of SPBP is sufficient to transactivate a minimal promoter containing a single copy of the SPRE, as well as the full-length stromelysin promoter.

SIGNOR-266223

P04637

O14965

0

phosphorylation

up-regulates activity

0.778

The N-terminus of E2F1 can interact directly with a region towards the C-terminus of p53, resulting in increased nuclear retention of p53 and p53-mediated transcription and apoptosis. This is inhibited by competition between p53 and cyclin A at the binding site within E2F19,10. The interaction between p53 and E2F1 is enhanced by phosphorylation of p53 on Ser315, a residue within the E2F1 binding region that is phosphorylated by cell cycle kinases such as cdk1, cdk2, cdk9 and Aurora kinase A

SIGNOR-120836

Q12857

Q13562

1

transcriptional regulation

up-regulates quantity

0.284

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

SIGNOR-268890

P11831

P68400

0

phosphorylation

up-regulates activity

0.552

Casein kinase II (CKII) phosphorylates the mammalian transcription factor serum response factor (SRF) on a serine residue(s) located within a region of the protein spanning amino acids 70 to 92, thereby enhancing its DNA-binding activity in vitro.| Nevertheless, additional mutation of serines 77 and 79 was required before phosphorylation and enhanced binding were completely abolished. Thus, serines 77 and 79 could also be recognized by CKII if serines 83 and 85 were mutated.

SIGNOR-250955

Q13131

Q9NR19

1

phosphorylation

up-regulates activity

0.275

This translocation is mediated by AMP-activated protein kinase (AMPK)-dependent ACSS2 Ser659 phosphorylation and subsequent exposure of the nuclear localization signal of ACSS2 to KPNA1/importin α5 for binding. In the nucleus, ACSS2 forms a complex with TFEB (transcription factor EB) and utilizes the acetate generated from histone deacetylation to locally produce acetyl-CoA for histone acetylation in the promoter regions of TFEB target genes.

SIGNOR-271822

Q86Y07

O75531

1

phosphorylation

down-regulates

0.502

We demonstrate that phosphorylation of ser4 and/or thr2/thr3 abrogates the interaction of baf with dna and reduces its interaction with the lem domain. Coexpression of vrk1 and gfp-baf greatly diminishes the association of baf with the nuclear chromatin/matrix and leads to its dispersal throughout the cell

SIGNOR-143368

P63162

O15355

0

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

P40763

P45984

0

phosphorylation

up-regulates

0.482

Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

SIGNOR-179275

P35372

P02775

0

chemical inhibition

down-regulates activity

0.385

Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors.

SIGNOR-258413

Q15418

P01100

1

phosphorylation

up-regulates activity

0.529

We now provide evidence that two growth-regulated, nucleus- and cytoplasm-localized protein kinases, 90-kda ribosomal s6 kinase (rsk) and mitogen-activated protein kinase (map kinase), contribute to the serum-induced phosphorylation of c-fos. The major phosphopeptides derived from biosynthetically labeled c-fos correspond to phosphopeptides generated after phosphorylation of c-fos in vitro with both rsk and map kinase. The phosphorylation sites identified for rsk (ser-362) and map kinase (ser-374) are in the transrepression domain. Cooperative phosphorylation at these sites by both enzymes was observed in vitro and reflected in vivo by the predominance of the peptide phosphorylated on both sites, as opposed to singly phosphorylated peptides. This study suggests a role for nuclear rsk and map kinase in modulating newly synthesized c-fos phosphorylation and downstream signaling.

SIGNOR-37154

P18850

Q16539

0

phosphorylation

up-regulates activity

0.585

This observation not only confirms the specific role for IFN-γ-induced p38 MAPK-dependent phosphorylation of ATF6 at the T166 site but also indicates a connection between phosphorylation and proteolytic activation.

SIGNOR-276841