GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q13285	P11511	1	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
O00165	Q05655	0	phosphorylation	down-regulates quantity by destabilization	0.2	FBXO25 encodes an orphan F-box protein that determines the substrate specificity of the SCF (SKP1-CUL1-F-box)(FBXO25) ubiquitin ligase complex. An unbiased screen uncovered the prosurvival protein HCLS1-associated protein X-1 (HAX-1) as the bona fide substrate of FBXO25 that is targeted after apoptotic stresses. Protein kinase Cdelta (PRKCD) initiates this process by phosphorylating FBXO25 and HAX-1, thereby spatially directing nuclear FBXO25 to mitochondrial HAX-1.\|Accordingly, PRKCD-induced phosphorylation of Hax-1 at Ser210 and Fbxo25 at Ser178 was associated with decreased expression of Hax-1 in control cells,	SIGNOR-275562
Q15046	P27361	0	phosphorylation	up-regulates	0.2	Lysrs serves as a key signaling molecule in the immune response by regulating gene expression. Lysrs was phosphorylated on serine 207 in a mapk-dependent manner, released from the multisynthetase complex, and translocated into the nucleus.	SIGNOR-186125
Q5JUK2	P21754	1	transcriptional regulation	up-regulates quantity by expression	0.378	Cotransfection of a mouse Sohlh1 expression vector with E box-containing promoter regions of mouse Lhx8, Zp1, and Zp3 fused to luciferase resulted in significant transactivation . Mutation of the E box sequences abolished SOHLH1-dependent stimulation. Thus, Lhx8, Zp1, and Zp3 are likely direct downstream target genes of SOHLH1 through the E box elements in their promoters.	SIGNOR-266078
Q9UK80	Q86WV6	1	deubiquitination	down-regulates activity	0.2	In this study, we found that USP21 is an important deubiquitinating enzyme for STING and that it negatively regulates the DNA virus-induced production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STING. HSV-1 infection recruited USP21 to STING at late stage by p38-mediated phosphorylation of USP21 at Ser538. I	SIGNOR-273671
P09619	P46108	2	binding	up-regulates	0.609	Crk could bind to both pdgf alpha- and beta-receptors in vivo	SIGNOR-75884
P12259	P68400	0	phosphorylation	down-regulates activity	0.307	Factor Va, the essential cofactor for prothrombinase, is phosphorylated on the acidic COOH terminus of the heavy chain of the cofactor, at Ser692, by a platelet membrane-associated casein kinase II (CKII). \| The phosphorylated cofactor has increased susceptibility to inactivation by activated protein C, since phosphorylated factor Va was found to be inactivated approximately 3-fold faster than its native counterpart.	SIGNOR-250862
Q8IVF5	P63000	1	guanine nucleotide exchange factor	up-regulates activity	0.589	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-260578
Q15042	Q8TDJ6	2	binding	up-regulates quantity	0.54	We isolated here a novel protein that was co-immunoprecipitated with Rab3 GEP and GAP by their respective antibodies from the crude synaptic vesicle fraction of rat brain. The protein, named rabconnectin-3, bound both Rab3 GEP and GAP. These results indicate that rabconnectin-3 serves as a scaffold molecule for both Rab3 GEP and GAP on synaptic vesicles.	SIGNOR-265582
Q16777	Q86Y13	0	monoubiquitination	up-regulates activity	0.2	2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.	SIGNOR-271754
P63000	P51149	2	binding	up-regulates activity	0.277	Rab7-Rac1 interaction may mediate late endosomal transport between microtubules and microfilaments	SIGNOR-261304
Q8N3U4	Q9NP77	0	dephosphorylation	up-regulates activity	0.298	Additional experiments revealed that Ssu72 directly interacts with Rad21 and SA2 in vitro and in vivo, and associates with sister chromatids in human cells. Interestingly, depletion or mutational inactivation of Ssu72 phosphatase activity caused the premature resolution of sister chromatid arm cohesion, whereas the overexpression of Ssu72 yielded high resistance to this resolution.\|anti‐phospho SA2 serine 1224	SIGNOR-275531
Q16790	P17612	0	phosphorylation	up-regulates	0.2	Here, we report that thr443 phosphorylation at the intracellular domain of ca ix by protein kinase a (pka) is critical for its activation in hypoxic cells, with the fullest activity of ca ix also requiring dephosphorylation of ser448.	SIGNOR-176973
P12931	Q969H4	1	phosphorylation	up-regulates activity	0.506	We identified Tyr 26 as a PDGF-induced and, additionally, Tyr 519 and Tyr 665 as SRC-induced tyrosine phosphorylation sites. Phosphomimetic mutants indicate that phosphorylation of Tyr 519 recruits CNK1 to the nucleus and additional phosphorylation of Tyr 26 enables CNK1 to promote SRE-dependent gene expression.	SIGNOR-275918
P04637	Q86UR1	1	transcriptional regulation	up-regulates quantity by expression	0.26	As a transcription factor, p53 induces several pro-apoptotic Bcl-2 members including Bax, Puma, Noxa and Bid, and represses the transcription of certain anti-apoptotic genes, including those encoding Bcl-2, Bcl-xL and survivin 3_and_5.	SIGNOR-209687
O60566	P25054	1	phosphorylation	up-regulates activity	0.428	These findings support a model in which BubR1 kinase may directly regulate APC function involved in stable kinetochore microtubule attachment.\|Using purified components, BubR1 directly phosphorylates APC and forms a ternary complex with APC and microtubules.	SIGNOR-279393
P28702	P10827	2	binding	up-regulates	0.649	Like many receptors belonging to the superfamily of steroid/thyroid nuclear receptors, thyroid hormone receptors (trs) bind to specific th-dna responsive elements (tre) upstream of target gene in heterodimeric complex with the 9-cis retinoid acid receptor (rxr	SIGNOR-81452
P09471	P08908	2	binding	up-regulates activity	0.447	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256972
O00206	O00206	2	binding	up-regulates	0.2	Upon activation, tlrs hetero- or homodimerize inducing the recruitment of adaptor proteins via the cytoplasmic tir domain	SIGNOR-203484
Q13976	Q15637	1	phosphorylation	down-regulates activity	0.438	PKG phosphorylates SF1 at Ser20, which inhibits the SF1-U2AF65 interaction leading to a block of pre-spliceosome assembly. Mutation of Ser20 to Ala or Thr also inhibits the interaction with U2AF65, indicating that Ser20 is essential for binding.	SIGNOR-249018
Q9UIC8	P62714	1	methylation	up-regulates activity	0.661	Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits \|The PP2A core enzyme was methylated by a PP2A-specific leucine carboxyl methyltransferase (LCMT1)	SIGNOR-265751
Q06330	Q9Y5J3	2	binding	down-regulates	0.657	These findings suggest a novel mechanism for negative feedback on notch signaling that requires rbp-jkappa to interact physically with hrt and hes.	SIGNOR-146687
P50406	P09471	2	binding	up-regulates activity	0.252	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257186
P04637	Q9H2G2	0	phosphorylation	up-regulates activity	0.256	The Ste20 like kinase SLK promotes p53 transactivation and apoptosis.\|Thus SLK induces p53 phosphorylation and transactivation, which enhances apoptosis after in vitro ischemia-reperfusion injury.	SIGNOR-279285
P08047	O00571	2	binding	up-regulates activity	0.353	DDX3X enhances transcription by interacting with transcription factors to promote their binding to the promoter of the target gene. The best characterized mechanism is its cooperation with the transcription factor SP1. The downstream genes of DDX3X-SP1-mediated transactivation include P21, KRAS, and MDM2	SIGNOR-269202
Q06330	Q16539	0	phosphorylation	down-regulates quantity by destabilization	0.247	P38 MAPK phosphorylates RBP-Jk at Thr339 by physical binding, which subsequently induces the degradation and ubiquitylation of the RBP-Jk protein.	SIGNOR-276403
Q9BZL6	Q13563	1	phosphorylation	up-regulates activity	0.2	Here, we report the identification of a previously unrecognized phosphorylation site within the polycystin-2 C terminus (Ser801), and we demonstrate that it is phosphorylated by protein kinase D. These results suggest that growth factor-stimulated, protein kinase D-mediated phosphorylation of polycystin-2 is essential for its ER channel function and links extracellular stimuli to its effects on cell growth and intracellular calcium regulation.	SIGNOR-276284
P53990	Q9UBP0	1	relocalization	up-regulates activity	0.519	Our results suggest that inclusion of IST1 into the ESCRT complex allows recruitment of spastin to promote fission of recycling tubules from the endosome. Thus, we reveal a novel cellular role for MT severing and identify a mechanism by which endosomal recycling can be coordinated with the degradative machinery.	SIGNOR-269047
O00330	P26367	2	binding	down-regulates activity	0.2	In the heterologous cell line BHK-21, Pdx1 inhibited by 60 to 80% the activation of the alpha-cell specific element G1 conferred by Pax-6 and/or Cdx-2/3. Although Pdx1 could bind three AT-rich motifs within G1, two of which are binding sites for Pax-6 and Cdx-2/3, the affinity of Pdx1 for G1 was much lower as compared to Pax-6. In addition, Pdx1 inhibited Pax-6 mediated activation through G3, to which Pdx1 was unable to bind. Moreover, a mutation impairing DNA binding of Pdx1 had no effect on its inhibition on Cdx-2/3. Since Pdx1 interacts directly with Pax-6 and Cdx-2/3 forming heterodimers, we suggest that Pdx1 inhibits glucagon gene transcription through protein to protein interactions with Pax-6 and Cdx-2/3.	SIGNOR-254903
Q14694	Q13315	0	phosphorylation	up-regulates quantity by stabilization	0.252	The translocation and stabilization of USP10 is regulated by ATM -mediated phosphorylation of USP10 at Thr42 and Ser337.	SIGNOR-276276
P29317	Q15418	0	phosphorylation	up-regulates activity	0.292	These comprehensive analyses indicate that high matrix stiffness activates ERK/RSK1-mediated EPHA2 non-canonical signalling to induce LYN activation, TWIST1 nuclear localization, and cell invasion (Fig. 6M).\|We next knocked down the most abundant RSK family members and found that loss of RSK1, but not RSK2 or RSK3, drastically inhibited EPHA2 S897 phosphorylation, prevented ECM stiffness-induced LYN activation and recruitment to EPHA2, and inhibited cell EMT and invasion induced by increasing rigidities (Fig. 6F\u2013I and S6H\u2013L).	SIGNOR-280113
O00743	P78527	1	dephosphorylation	up-regulates activity	0.538	In addition, siRNA knockdown of either PP6R1 or PP6 significantly decreased IR activation of DNA-PK, suggesting that PP6 activates DNA-PK by association and dephosphorylation.\|PP6 may dephosphorylate sites in DNA-PKcs to reduce binding with heterodimer Ku proteins, because DNA-PK activation completely depends on Ku-mediated complex formation with DNA.	SIGNOR-277164
P04626	P62993	1	relocalization	up-regulates	0.85	All erbb ligands and receptors couple to activation of the ras-mapk pathway, either directly through sh2 domain-mediated recruitment of grb-2 or indirectly through ptb domain-mediated binding of the shc adaptor	SIGNOR-121968
P36897	Q01082	1	phosphorylation	up-regulates	0.522	This suggests that, upon stimulation with tgf-beta1, phosphorylation of elf could induce a conformational change that reduces its affinity for ankyrin and tropomyosin and facilitates an association with smad3 and smad4 instead.	SIGNOR-97626
Q92993	P06493	0	phosphorylation	up-regulates	0.478	Moreover, app stabilized tip60 through cdk-dependent phosphorylation	SIGNOR-139653
P31645	P12931	0	phosphorylation	up-regulates quantity by stabilization	0.258	We found that 1) SERT exists in a tyrosine-phosphorylated form, 2) inhibition of tyrosine kinase(s) reduces SERT expression levels by facilitating SERT protein degradation, 3) Src-kinase activity up-regulates SERT protein expression with a concomitant increase in 5-HT uptake and tyrosine phosphorylation, and 4) mutation of Tyr47 or Tyr142 abolishes src-induced increases in transport function and phosphorylation of SERT.	SIGNOR-276386
Q9BRP0	Q00987	0	ubiquitination	down-regulates quantity by destabilization	0.2	In breast cancer cells, MDM2 overexpression or p53 KD reduced OVOL2 protein expression, and the proteasome inhibitor MG132 blocked the MDM2 overexpression\u2010 or p53 KD\u2010mediated reduction in OVOL2 expression (Figure\u00a06B,C).\|The E3 ubiquitin ligase MDM2 ubiquitinates and degrades the OVOL2 protein.	SIGNOR-278826
Q13131	P08151	1	phosphorylation	down-regulates activity	0.334	AMPK phosphorylates GLI1 at serines 102 and 408 and threonine 1074. Mutation of these three sites into alanine prevents phosphorylation by AMPK. This in turn leads to increased GLI1 protein stability, transcriptional activity, and oncogenic potency.	SIGNOR-259862
O00187	P0C0L5	1	cleavage	up-regulates activity	0.798	MASP-2 cleaves C4 releasing C4a and generating C4b, which attaches covalently to the pathogen surface upon exposure of its reactive thioester. C2 binds to C4b and is also cleaved by MASP-2 to form the C3 convertase (C4b2a).	SIGNOR-263422
P18848	Q15031	1	transcriptional regulation	up-regulates quantity by expression	0.251	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269421
Q02750	Q9BRX9	2	binding	up-regulates	0.526	Morg1 specifically associates with several components of the erk pathway, including mp1, raf-1, mek, and erk, and stabilizes their assembly into an oligomeric complex.	SIGNOR-124470
Q16236	Q86TM6	0	ubiquitination	down-regulates quantity by destabilization	0.2	NRF2 is negatively regulated by three E3 ubiquitin ligase complexes: the KEAP1-CUL3-RBX1 complex, the β-TrCP-SKP1-CUL1-RBX1 complex, and HRD1.	SIGNOR-267360
Q00987	Q9GZR7	1	polyubiquitination	up-regulates activity	0.334	MDM2 mediates nonproteolytic polyubiquitylation of the DEAD-Box RNA helicase DDX24. Unexpectedly, however, the polyubiquitylation of DDX24 did not elicit its proteasomal degradation but rather promoted its association with preribosomal ribonucleoprotein (pre-rRNP) processing complexes that are required for the early steps of pre-rRNA processing.	SIGNOR-272845
P45983	P98177	1	phosphorylation	up-regulates	0.612	Upon treatment of cells with h2o2, the small gtpase ral is activated and this results in a jnk-dependent phosphorylation of foxo4 on threonine 447 and threonine 451. This ral-mediated, jnk-dependent phosphorylation is involved in the nuclear translocation and transcriptional activation of foxo4 after h2o2 treatment.	SIGNOR-130385
P04083	P05129	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-202788
P01042	P30411	2	binding	up-regulates activity	0.857	BK binds receptor B2 (B2R) and triggers inflammation, edema, and symptoms of anaphylaxis.	SIGNOR-263554
Q92830	P0DPK2	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-269597
Q99683	O14733	1	phosphorylation	up-regulates	0.594	Ask1 is a member of a mapkkk family and functions as an upstream kinase engaged in c-jun nh2-terminal kinase (jnk)/p38 signaling via the phosphorylation and activation of mapkks, such as mkk3, -4, -6, and -7	SIGNOR-161766
O15550	O43248	1	transcriptional regulation	up-regulates quantity by expression	0.302	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-260026
Q16539	P24522	2	binding	down-regulates	0.461	Gadd45alfa appears to act as an endogenous inhibitor of the alternative p38alfa-activation pathway in t-cell, by binding to p38alfa and preventing tyr323 phosphorilation	SIGNOR-166584
Q8TDY4	Q9P289	0	phosphorylation	up-regulates activity	0.2	Here we show that MST4 phosphorylates ACAP4, an ARF6 GTPase-activating protein, at Thr545\|Significantly, phosphorylation of Thr545 enables ACAP4 to interact with ezrin. Given the location of Thr545 between the GTPase-activating protein domain and the first ankyrin repeat, we reason that MST4 phosphorylation elicits a conformational change that enables ezrin-ACAP4 interaction.	SIGNOR-272238
P10909	Q8N668	2	binding	down-regulates quantity by destabilization	0.392	CLU-2 is a ubiquitin binding protein (UBP) that enhances proteasome activity. sCLU promotes degradation of COMMD1. sCLU interacts with the SCF-βTrCP E3 ligase complex, serving as a scaffolding chaperone to form a multimeric protein complex that facilitates COMMD1 and I-κB ubiquitination and proteasomal degradation.	SIGNOR-271432
O14798	P50591	2	binding	down-regulates	0.899	Albeit on binding the ligand, dcr1 and dcr2 do not transduce the apoptogenic signal,	SIGNOR-163611
Q9UBY5	Q03113	2	binding	up-regulates	0.467	Serum-borne lysophosphatidic acid (lpa) and sphingosine 1-phosphophate (s1p) act through g12/13-coupled receptors to inhibit the hippo pathway kinases lats1/2 thereby activating yap and taz transcription co-activators, which are oncoproteins repressed by lats1/2.	SIGNOR-198544
Q96GD4	O60879	1	phosphorylation	up-regulates	0.288	The microtubule binding fh2 domain of mdia3 is phosphorylated by aurora b kinase in vitro, and cells expressing the nonphosphorylatable mdia3 mutant cannot position chromosomes at the metaphase plate	SIGNOR-172803
O00755	Q13309	2	binding	down-regulates activity	0.2	These findings suggested that Wnt7a upregulated P21 and P27 by inactivating SKP2.	SIGNOR-278876
Q2TAL8	Q9Y2Z4	1	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269413
P04629	Q8WU20	2	binding	up-regulates	0.779	The signaling adapter frs-2 competes with shc for binding to the nerve growth factor receptor trka:a model for discriminating proliferation and differentiation	SIGNOR-65955
O15169	Q9NTX7	0	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
O43511	Q99942	0	ubiquitination	down-regulates quantity by destabilization	0.2	E3 ubiquitin ligase Rma1 is involved in Pendrin degradation	SIGNOR-271497
Q9NYA1	Q8TD94	0	transcriptional regulation	up-regulates quantity by expression	0.2	KLF14 Is a Transcriptional Activator of SK1 Gene Expression in Endothelial Cells	SIGNOR-266047
O14936	Q02410	2	binding	up-regulates activity	0.851	Interaction with Munc18 increases Mint1 binding to CASK.	SIGNOR-264041
P08709	P00740	2	binding	up-regulates activity	0.55	TF has a high affinity for FVII and enables the trace levels (∼1% of the total FVII) of activated FVII (FVIIa) in the blood to cleave specific sites in the serine proteases FIX and FX, activating them into FIXa and FXa, respectively.	SIGNOR-263544
Q00987	Q6K0P9	2	binding	down-regulates quantity by destabilization	0.414	Here, we show that IFIXalpha1 downregulates HDM2, a principal negative regulator of p53, at the posttranslational level. IFIXalpha1 destabilizes HDM2 protein and promotes its ubiquitination. The E3 ligase activity of HDM2 appears to be required for this IFIXalpha1 effect. Importantly, HDM2 downregulation is required for the IFIXalpha1-mediated increase of p53 protein levels, transcriptional activity, and nuclear localization, suggesting that IFIXalpha1 positively regulates p53 by acting as a negative regulator of HDM2.	SIGNOR-268493
P49755	Q9Y3A6	2	binding	up-regulates activity	0.568	P28 forms hetero-oligomeric complexes with p23. p23 is a major determinant for efficient targeting of p28 to the ERGIC	SIGNOR-261298
Q14765	O60674	0	phosphorylation	up-regulates	0.676	Janus family tyrosine kinases jak2 and tyk2, which in turn phosphorylate stat4 on tyrosine 693. The p38 mitogen-activated protein kinase (mapk) signaling pathway is also activated in response to il-12, followed by phosphorylation of stat4 on serine 721, which is required for stat4 full transcriptional activity	SIGNOR-142736
Q9UHD2	K9N643	2	binding	down-regulates activity	0.2	Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε, and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm	SIGNOR-260593
P27361	P00533	1	phosphorylation	down-regulates	0.557	It is likely that the map2 and ert kinases account for the phosphorylation of the egf receptor at thr669 (egf receptor (krel veplt669psgeapnqallr)) observed in cultured cells.Phosphorylation at ser-695 is partial and occurs only if thr-693 is phosphorylated. Phosphorylation at thr-678 and thr-693 by prkd1 inhibits egf-induced mapk8/jnk1 activation.	SIGNOR-20549
P31749	O15530	0	phosphorylation	up-regulates	0.748	We have partially purified a kinase from brain extract that phosphorylates Ser473 of PKBalpha in a PtdIns(3,4,5)P3-dependent manner and that is immunoprecipitated with PDK1 antibodies.	SIGNOR-67367
Q02078	P11802	2	binding	down-regulates	0.284	In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms.	SIGNOR-176515
P28482	P24928	1	phosphorylation	down-regulates	0.311	Erk1/2 are major ser-5 kinases after h2o2 treatment. These results suggest that subsequent to h2o2 treatment, the ser-5-phosphorylated form, but not the ser-2-phosphorylated form or the unphosphorylated form, is targeted for rapid proteasomal degradation through its ubiquitination.	SIGNOR-120160
Q05682	Q9UQM7	0	phosphorylation	down-regulates	0.2	Smooth muscle caldesmon was phosphorylated by smooth muscle calmodulin-dependent protein kinase. Ii	SIGNOR-22635
P14210	Q02447	0	transcriptional regulation	up-regulates quantity by expression	0.2	Furthermore, in transient cotransfection assays, overexpression of Sp1 and/or Sp3 stimulated HGF promoter activity independently and additively through binding to the Sp1 binding site in the HGF gene promoter region.	SIGNOR-251741
Q92794	Q01196	2	binding	up-regulates	0.465	The activation domain of aml1 is required for its interaction with moz / moz activates aml1_mediated transcription	SIGNOR-113056
Q08209	P53805	2	binding	down-regulates activity	0.633	MCIP proteins can bind to and inhibit calcineurin, a calcium/calmodulin-regulated serine/threonine protein phosphatase that is activated during cardiac hypertrophy and failure	SIGNOR-252025
Q92529	P04626	0	relocalization	up-regulates	0.549	Erbb3 is characterized by a large number of binding sites for phosphatidylinositol-3-kinase (pi3k), while erbb2 has only few interaction partners with shc as the most frequent one.	SIGNOR-146855
Q15654	Q12923	0	dephosphorylation	down-regulates activity	0.434	PTPL1/FAP-1 negatively regulates TRIP6 function in lysophosphatidic acid-induced cell migration.\|Here we further demonstrate that a switch from c-Src-mediated phosphorylation to PTPL1/Fas-associated phosphatase-1-dependent dephosphorylation serves as an inhibitory feedback control mechanism of TRIP6 function in LPA-induced cell migration. PTPL1 dephosphorylates phosphotyrosine 55 of TRIP6 in vitro and inhibits LPA-induced tyrosine phosphorylation of TRIP6 in cells.	SIGNOR-248713
P15172	Q92831	2	binding	up-regulates	0.647	Our results provide direct evidence that myod acetylation functionally activates the protein and show that both pcaf and cbp/p300 are candidate enzymes for myod acetylation in vivo	SIGNOR-81059
Q96EP0	Q14790	0	cleavage	down-regulates activity	0.315	We show that LUBAC interacted with caspase-1 via HOIP and modified its CARD domain with linear polyubiquitin and that depletion of HOIP or Sharpin resulted in heightened caspase-1 activation and cell death in response to inflammasome activation, unlike what is observed in macrophages. Reciprocally, caspase-1, as well as caspase-8, regulated LUBAC activity by proteolytically processing HOIP at Asp-348 and Asp-387 during the execution of cell death.	SIGNOR-272194
Q9NQU5	O43426	1	phosphorylation	up-regulates activity	0.2	We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo.	SIGNOR-263022
Q9NPG1	O00744	2	binding	up-regulates	0.617	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-131625
Q06124	Q9UJC3	2	binding	down-regulates activity	0.353	The protein-tyrosine phosphatase domain and N-terminal SH2 domain of SHP2 directly interacted with Hook1. Down-regulation of Hook1 increased SHP2 activity. These results suggested that Hook1 was an endogenous negative regulator of SHP2 phosphatase activity.	SIGNOR-260642
P23246	P49840	0	phosphorylation	down-regulates	0.2	Psf is directly phosphorylated by gsk3, thus promoting interaction of psf with trap150, which prevents psf from binding cd45 pre-mrna. / threonine phosphorylation of psf by gsk3 primarily occurs on residue t687	SIGNOR-168385
Q9H2X6	Q09472	1	phosphorylation	up-regulates activity	0.611	Furthermore, HIPK2 forms a complex with the coactivator p300 and AML1, phosphorylates p300 at multiple Serine/Threonine sites and activates p300 HAT activity and coactivator function.	SIGNOR-278943
P05164	P02647	1	oxidation	down-regulates activity	0.406	When apolipoprotein A-I (apoA-I), the major HDL protein, was oxidized by MPO, its ability to promote cellular cholesterol efflux by ABCA1 was impaired. Moreover, oxidized apoA-I was unable to activate lecithin:cholesterol acyltransferase (LCAT), which rapidly converts free cholesterol to cholesteryl ester, a critical step in HDL maturation	SIGNOR-252102
Q13185	P68431	2	binding	up-regulates activity	0.2	A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing.	SIGNOR-264496
Q92847	O00230	2	binding	up-regulates	0.471	In human tissues cst-14 as well as cst-17 but not ss-14 bind the gh secretagogue receptor (ghs-r).	SIGNOR-91134
P10415	P27361	0	phosphorylation	up-regulates	0.56	Erk1 and erk2 directly phosphorylate bcl2 exclusively at ser-70 p44mapk/extracellular signal-regulated kinase 1 (erk1) and p42 mapk/erk2 are activated by il-3, colocalize with mitochondrial bcl2, and can directly phosphorylate bcl2 on ser-70 in a stauro-resistant manner both in vitro and in vivo molecular association.	SIGNOR-74935
Q03113	O00254	2	binding	up-regulates activity	0.385	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257409
Q8NBJ5	P08123	1	glycosylation	up-regulates activity	0.429	Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.	SIGNOR-261153
P04004	P17252	0	phosphorylation	up-regulates quantity by stabilization	0.318	Phosphorylation of vitronectin on Ser362 by protein kinase C attenuates its cleavage by plasmin.	SIGNOR-248962
Q92786	Q9Y478	0	phosphorylation	down-regulates quantity by destabilization	0.2	Furthermore, the Ser79 phosphorylation of PROX1 by AMPK enhances the recruitment of CUL4-DDB1 ubiquitin ligase to promote PROX1 degradation.	SIGNOR-277609
O15554	P17612	0	phosphorylation	down-regulates activity	0.2	Mutating the single PKA site (S334A) in human KCa3.1 abolished the PKA-dependent regulation. CaM-affinity chromatography showed that CaM binding to KCa3.1 was decreased by PKA-dependent phosphorylation of S334, and this regulation was absent in the S334A mutant.The results above indicate that PKA activation led to a phosphorylation event that inhibited KCa3.1 channel activity	SIGNOR-276855
P06493	Q92993	1	phosphorylation	up-regulates	0.478	Moreover, app stabilized tip60 through cdk-dependent phosphorylation	SIGNOR-139653
P23588	Q14004	0	phosphorylation	up-regulates activity	0.251	CDK13 directly phosphorylates 4E-BP1 at Thr46 and eIF4B at Ser422; genetically or pharmacologically inhibiting CDK13 disrupts mRNA translation.	SIGNOR-273115
P54764	P52803	2	binding	up-regulates	0.945	Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor	SIGNOR-52473
P62826	O96013	0	phosphorylation	up-regulates	0.308	We show that ran is a substrate for p21-activated kinase 4 (pak4) and that its phosphorylation on serine-135 increases during mitosis.Altogether, our findings strongly suggest that pak4-mediated phosphorylation of gdp- or gtp-bound ran modulates the assembly of complexes that are required at specific subcellular localizations for ran to carry out its functions during mitotic progression.	SIGNOR-167667
P18850	Q16549	0	phosphorylation	up-regulates	0.2	We discovered that azc, an agent that causes the formation of abnormal proteins, stimulates the stress-activated kinase p38 mapk, which phosphorylates atf6	SIGNOR-89813
O60907	P35222	2	binding	up-regulates activity	0.659	TBL1 appears to serve two roles in regulating the activity of β-catenin. Besides the initially identified role of TBL1 in recruiting β-catenin to the SCF(TBL1) complex, it has also been shown to function as a transcriptional co-activator of β-catenin in recruiting it to the promoter site of Wnt target genes. Our results indicated that TBL1 can inhibit the polyubiquitination of β-catenin by Siah-1 in vitro (Fig. 3) and stabilize β-catenin in cells by protecting it from Siah-1-mediated ubiquitination and proteasomal degradation (Fig. 4).	SIGNOR-271954
P12931	Q9NZC7	1	phosphorylation	up-regulates	0.48	The tyrosine kinase, src, phosphorylates wwox at tyrosine 33 in the first ww domain and enhances its binding to p73.	SIGNOR-123819

Q13285

P11511

1

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

O00165

Q05655

0

phosphorylation

down-regulates quantity by destabilization

0.2

FBXO25 encodes an orphan F-box protein that determines the substrate specificity of the SCF (SKP1-CUL1-F-box)(FBXO25) ubiquitin ligase complex. An unbiased screen uncovered the prosurvival protein HCLS1-associated protein X-1 (HAX-1) as the bona fide substrate of FBXO25 that is targeted after apoptotic stresses. Protein kinase Cdelta (PRKCD) initiates this process by phosphorylating FBXO25 and HAX-1, thereby spatially directing nuclear FBXO25 to mitochondrial HAX-1.|Accordingly, PRKCD-induced phosphorylation of Hax-1 at Ser210 and Fbxo25 at Ser178 was associated with decreased expression of Hax-1 in control cells,

SIGNOR-275562

Q15046

P27361

0

phosphorylation

up-regulates

0.2

Lysrs serves as a key signaling molecule in the immune response by regulating gene expression. Lysrs was phosphorylated on serine 207 in a mapk-dependent manner, released from the multisynthetase complex, and translocated into the nucleus.

SIGNOR-186125

Q5JUK2

P21754

1

transcriptional regulation

up-regulates quantity by expression

0.378

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

SIGNOR-266078

Q9UK80

Q86WV6

1

deubiquitination

down-regulates activity

0.2

In this study, we found that USP21 is an important deubiquitinating enzyme for STING and that it negatively regulates the DNA virus-induced production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STING. HSV-1 infection recruited USP21 to STING at late stage by p38-mediated phosphorylation of USP21 at Ser538. I

SIGNOR-273671

P09619

P46108

2

binding

up-regulates

0.609

Crk could bind to both pdgf alpha- and beta-receptors in vivo

SIGNOR-75884

P12259

P68400

0

phosphorylation

down-regulates activity

0.307

Factor Va, the essential cofactor for prothrombinase, is phosphorylated on the acidic COOH terminus of the heavy chain of the cofactor, at Ser692, by a platelet membrane-associated casein kinase II (CKII). | The phosphorylated cofactor has increased susceptibility to inactivation by activated protein C, since phosphorylated factor Va was found to be inactivated approximately 3-fold faster than its native counterpart.

SIGNOR-250862

Q8IVF5

P63000

1

guanine nucleotide exchange factor

up-regulates activity

0.589

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-260578

Q15042

Q8TDJ6

2

binding

up-regulates quantity

0.54

We isolated here a novel protein that was co-immunoprecipitated with Rab3 GEP and GAP by their respective antibodies from the crude synaptic vesicle fraction of rat brain. The protein, named rabconnectin-3, bound both Rab3 GEP and GAP. These results indicate that rabconnectin-3 serves as a scaffold molecule for both Rab3 GEP and GAP on synaptic vesicles.

SIGNOR-265582

Q16777

Q86Y13

0

monoubiquitination

up-regulates activity

0.2

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

SIGNOR-271754

P63000

P51149

2

binding

up-regulates activity

0.277

Rab7-Rac1 interaction may mediate late endosomal transport between microtubules and microfilaments

SIGNOR-261304

Q8N3U4

Q9NP77

0

dephosphorylation

up-regulates activity

0.298

Additional experiments revealed that Ssu72 directly interacts with Rad21 and SA2 in vitro and in vivo, and associates with sister chromatids in human cells. Interestingly, depletion or mutational inactivation of Ssu72 phosphatase activity caused the premature resolution of sister chromatid arm cohesion, whereas the overexpression of Ssu72 yielded high resistance to this resolution.|anti‐phospho SA2 serine 1224

SIGNOR-275531

Q16790

P17612

0

phosphorylation

up-regulates

0.2

Here, we report that thr443 phosphorylation at the intracellular domain of ca ix by protein kinase a (pka) is critical for its activation in hypoxic cells, with the fullest activity of ca ix also requiring dephosphorylation of ser448.

SIGNOR-176973

P12931

Q969H4

1

phosphorylation

up-regulates activity

0.506

We identified Tyr 26 as a PDGF-induced and, additionally, Tyr 519 and Tyr 665 as SRC-induced tyrosine phosphorylation sites. Phosphomimetic mutants indicate that phosphorylation of Tyr 519 recruits CNK1 to the nucleus and additional phosphorylation of Tyr 26 enables CNK1 to promote SRE-dependent gene expression.

SIGNOR-275918

P04637

Q86UR1

1

transcriptional regulation

up-regulates quantity by expression

0.26

As a transcription factor, p53 induces several pro-apoptotic Bcl-2 members including Bax, Puma, Noxa and Bid, and represses the transcription of certain anti-apoptotic genes, including those encoding Bcl-2, Bcl-xL and survivin 3_and_5.

SIGNOR-209687

O60566

P25054

1

phosphorylation

up-regulates activity

0.428

These findings support a model in which BubR1 kinase may directly regulate APC function involved in stable kinetochore microtubule attachment.|Using purified components, BubR1 directly phosphorylates APC and forms a ternary complex with APC and microtubules.

SIGNOR-279393

P28702

P10827

2

binding

up-regulates

0.649

Like many receptors belonging to the superfamily of steroid/thyroid nuclear receptors, thyroid hormone receptors (trs) bind to specific th-dna responsive elements (tre) upstream of target gene in heterodimeric complex with the 9-cis retinoid acid receptor (rxr

SIGNOR-81452

P09471

P08908

2

binding

up-regulates activity

0.447

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256972

O00206

2

binding

up-regulates

0.2

Upon activation, tlrs hetero- or homodimerize inducing the recruitment of adaptor proteins via the cytoplasmic tir domain

SIGNOR-203484

Q13976

Q15637

1

phosphorylation

down-regulates activity

0.438

PKG phosphorylates SF1 at Ser20, which inhibits the SF1-U2AF65 interaction leading to a block of pre-spliceosome assembly. Mutation of Ser20 to Ala or Thr also inhibits the interaction with U2AF65, indicating that Ser20 is essential for binding.

SIGNOR-249018

Q9UIC8

P62714

1

methylation

up-regulates activity

0.661

Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits |The PP2A core enzyme was methylated by a PP2A-specific leucine carboxyl methyltransferase (LCMT1)

SIGNOR-265751

Q06330

Q9Y5J3

2

binding

down-regulates

0.657

These findings suggest a novel mechanism for negative feedback on notch signaling that requires rbp-jkappa to interact physically with hrt and hes.

SIGNOR-146687

P50406

P09471

2

binding

up-regulates activity

0.252

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257186

P04637

Q9H2G2

0

phosphorylation

up-regulates activity

0.256

The Ste20 like kinase SLK promotes p53 transactivation and apoptosis.|Thus SLK induces p53 phosphorylation and transactivation, which enhances apoptosis after in vitro ischemia-reperfusion injury.

SIGNOR-279285

P08047

O00571

2

binding

up-regulates activity

0.353

DDX3X enhances transcription by interacting with transcription factors to promote their binding to the promoter of the target gene. The best characterized mechanism is its cooperation with the transcription factor SP1. The downstream genes of DDX3X-SP1-mediated transactivation include P21, KRAS, and MDM2

SIGNOR-269202

Q06330

Q16539

0

phosphorylation

down-regulates quantity by destabilization

0.247

P38 MAPK phosphorylates RBP-Jk at Thr339 by physical binding, which subsequently induces the degradation and ubiquitylation of the RBP-Jk protein.

SIGNOR-276403

Q9BZL6

Q13563

1

phosphorylation

up-regulates activity

0.2

Here, we report the identification of a previously unrecognized phosphorylation site within the polycystin-2 C terminus (Ser801), and we demonstrate that it is phosphorylated by protein kinase D. These results suggest that growth factor-stimulated, protein kinase D-mediated phosphorylation of polycystin-2 is essential for its ER channel function and links extracellular stimuli to its effects on cell growth and intracellular calcium regulation.

SIGNOR-276284

P53990

Q9UBP0

1

relocalization

up-regulates activity

0.519

Our results suggest that inclusion of IST1 into the ESCRT complex allows recruitment of spastin to promote fission of recycling tubules from the endosome. Thus, we reveal a novel cellular role for MT severing and identify a mechanism by which endosomal recycling can be coordinated with the degradative machinery.

SIGNOR-269047

O00330

P26367

2

binding

down-regulates activity

0.2

In the heterologous cell line BHK-21, Pdx1 inhibited by 60 to 80% the activation of the alpha-cell specific element G1 conferred by Pax-6 and/or Cdx-2/3. Although Pdx1 could bind three AT-rich motifs within G1, two of which are binding sites for Pax-6 and Cdx-2/3, the affinity of Pdx1 for G1 was much lower as compared to Pax-6. In addition, Pdx1 inhibited Pax-6 mediated activation through G3, to which Pdx1 was unable to bind. Moreover, a mutation impairing DNA binding of Pdx1 had no effect on its inhibition on Cdx-2/3. Since Pdx1 interacts directly with Pax-6 and Cdx-2/3 forming heterodimers, we suggest that Pdx1 inhibits glucagon gene transcription through protein to protein interactions with Pax-6 and Cdx-2/3.

SIGNOR-254903

Q14694

Q13315

0

phosphorylation

up-regulates quantity by stabilization

0.252

The translocation and stabilization of USP10 is regulated by ATM -mediated phosphorylation of USP10 at Thr42 and Ser337.

SIGNOR-276276

P29317

Q15418

0

phosphorylation

up-regulates activity

0.292

These comprehensive analyses indicate that high matrix stiffness activates ERK/RSK1-mediated EPHA2 non-canonical signalling to induce LYN activation, TWIST1 nuclear localization, and cell invasion (Fig. 6M).|We next knocked down the most abundant RSK family members and found that loss of RSK1, but not RSK2 or RSK3, drastically inhibited EPHA2 S897 phosphorylation, prevented ECM stiffness-induced LYN activation and recruitment to EPHA2, and inhibited cell EMT and invasion induced by increasing rigidities (Fig. 6F\u2013I and S6H\u2013L).

SIGNOR-280113

O00743

P78527

1

dephosphorylation

up-regulates activity

0.538

In addition, siRNA knockdown of either PP6R1 or PP6 significantly decreased IR activation of DNA-PK, suggesting that PP6 activates DNA-PK by association and dephosphorylation.|PP6 may dephosphorylate sites in DNA-PKcs to reduce binding with heterodimer Ku proteins, because DNA-PK activation completely depends on Ku-mediated complex formation with DNA.

SIGNOR-277164

P04626

P62993

1

relocalization

up-regulates

0.85

All erbb ligands and receptors couple to activation of the ras-mapk pathway, either directly through sh2 domain-mediated recruitment of grb-2 or indirectly through ptb domain-mediated binding of the shc adaptor

SIGNOR-121968

P36897

Q01082

1

phosphorylation

up-regulates

0.522

This suggests that, upon stimulation with tgf-beta1, phosphorylation of elf could induce a conformational change that reduces its affinity for ankyrin and tropomyosin and facilitates an association with smad3 and smad4 instead.

SIGNOR-97626

Q92993

P06493

0

phosphorylation

up-regulates

0.478

Moreover, app stabilized tip60 through cdk-dependent phosphorylation

SIGNOR-139653

P31645

P12931

0

phosphorylation

up-regulates quantity by stabilization

0.258

We found that 1) SERT exists in a tyrosine-phosphorylated form, 2) inhibition of tyrosine kinase(s) reduces SERT expression levels by facilitating SERT protein degradation, 3) Src-kinase activity up-regulates SERT protein expression with a concomitant increase in 5-HT uptake and tyrosine phosphorylation, and 4) mutation of Tyr47 or Tyr142 abolishes src-induced increases in transport function and phosphorylation of SERT.

SIGNOR-276386

Q9BRP0

Q00987

0

ubiquitination

down-regulates quantity by destabilization

0.2

In breast cancer cells, MDM2 overexpression or p53 KD reduced OVOL2 protein expression, and the proteasome inhibitor MG132 blocked the MDM2 overexpression\u2010 or p53 KD\u2010mediated reduction in OVOL2 expression (Figure\u00a06B,C).|The E3 ubiquitin ligase MDM2 ubiquitinates and degrades the OVOL2 protein.

SIGNOR-278826

Q13131

P08151

1

phosphorylation

down-regulates activity

0.334

AMPK phosphorylates GLI1 at serines 102 and 408 and threonine 1074. Mutation of these three sites into alanine prevents phosphorylation by AMPK. This in turn leads to increased GLI1 protein stability, transcriptional activity, and oncogenic potency.

SIGNOR-259862

O00187

P0C0L5

1

cleavage

up-regulates activity

0.798

MASP-2 cleaves C4 releasing C4a and generating C4b, which attaches covalently to the pathogen surface upon exposure of its reactive thioester. C2 binds to C4b and is also cleaved by MASP-2 to form the C3 convertase (C4b2a).

SIGNOR-263422

P18848

Q15031

1

transcriptional regulation

up-regulates quantity by expression

0.251

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

SIGNOR-269421

Q02750

Q9BRX9

2

binding

up-regulates

0.526

Morg1 specifically associates with several components of the erk pathway, including mp1, raf-1, mek, and erk, and stabilizes their assembly into an oligomeric complex.

SIGNOR-124470

Q16236

Q86TM6

0

ubiquitination

down-regulates quantity by destabilization

0.2

NRF2 is negatively regulated by three E3 ubiquitin ligase complexes: the KEAP1-CUL3-RBX1 complex, the β-TrCP-SKP1-CUL1-RBX1 complex, and HRD1.

SIGNOR-267360

Q00987

Q9GZR7

1

polyubiquitination

up-regulates activity

0.334

MDM2 mediates nonproteolytic polyubiquitylation of the DEAD-Box RNA helicase DDX24. Unexpectedly, however, the polyubiquitylation of DDX24 did not elicit its proteasomal degradation but rather promoted its association with preribosomal ribonucleoprotein (pre-rRNP) processing complexes that are required for the early steps of pre-rRNA processing.

SIGNOR-272845

P45983

P98177

1

phosphorylation

up-regulates

0.612

Upon treatment of cells with h2o2, the small gtpase ral is activated and this results in a jnk-dependent phosphorylation of foxo4 on threonine 447 and threonine 451. This ral-mediated, jnk-dependent phosphorylation is involved in the nuclear translocation and transcriptional activation of foxo4 after h2o2 treatment.

SIGNOR-130385

P04083

P05129

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-202788

P01042

P30411

2

binding

up-regulates activity

0.857

BK binds receptor B2 (B2R) and triggers inflammation, edema, and symptoms of anaphylaxis.

SIGNOR-263554

Q92830

P0DPK2

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-269597

Q99683

O14733

1

phosphorylation

up-regulates

0.594

Ask1 is a member of a mapkkk family and functions as an upstream kinase engaged in c-jun nh2-terminal kinase (jnk)/p38 signaling via the phosphorylation and activation of mapkks, such as mkk3, -4, -6, and -7

SIGNOR-161766

O15550

O43248

1

transcriptional regulation

up-regulates quantity by expression

0.302

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-260026

Q16539

P24522

2

binding

down-regulates

0.461

Gadd45alfa appears to act as an endogenous inhibitor of the alternative p38alfa-activation pathway in t-cell, by binding to p38alfa and preventing tyr323 phosphorilation

SIGNOR-166584

Q8TDY4

Q9P289

0

phosphorylation

up-regulates activity

0.2

Here we show that MST4 phosphorylates ACAP4, an ARF6 GTPase-activating protein, at Thr545|Significantly, phosphorylation of Thr545 enables ACAP4 to interact with ezrin. Given the location of Thr545 between the GTPase-activating protein domain and the first ankyrin repeat, we reason that MST4 phosphorylation elicits a conformational change that enables ezrin-ACAP4 interaction.

SIGNOR-272238

P10909

Q8N668

2

binding

down-regulates quantity by destabilization

0.392

CLU-2 is a ubiquitin binding protein (UBP) that enhances proteasome activity. sCLU promotes degradation of COMMD1. sCLU interacts with the SCF-βTrCP E3 ligase complex, serving as a scaffolding chaperone to form a multimeric protein complex that facilitates COMMD1 and I-κB ubiquitination and proteasomal degradation.

SIGNOR-271432

O14798

P50591

2

binding

down-regulates

0.899

Albeit on binding the ligand, dcr1 and dcr2 do not transduce the apoptogenic signal,

SIGNOR-163611

Q9UBY5

Q03113

2

binding

up-regulates

0.467

Serum-borne lysophosphatidic acid (lpa) and sphingosine 1-phosphophate (s1p) act through g12/13-coupled receptors to inhibit the hippo pathway kinases lats1/2 thereby activating yap and taz transcription co-activators, which are oncoproteins repressed by lats1/2.

SIGNOR-198544

Q96GD4

O60879

1

phosphorylation

up-regulates

0.288

The microtubule binding fh2 domain of mdia3 is phosphorylated by aurora b kinase in vitro, and cells expressing the nonphosphorylatable mdia3 mutant cannot position chromosomes at the metaphase plate

SIGNOR-172803

O00755

Q13309

2

binding

down-regulates activity

0.2

These findings suggested that Wnt7a upregulated P21 and P27 by inactivating SKP2.

SIGNOR-278876

Q2TAL8

Q9Y2Z4

1

transcriptional regulation

up-regulates quantity by expression

0.2

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

SIGNOR-269413

P04629

Q8WU20

2

binding

up-regulates

0.779

The signaling adapter frs-2 competes with shc for binding to the nerve growth factor receptor trka:a model for discriminating proliferation and differentiation

SIGNOR-65955

O15169

Q9NTX7

0

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

O43511

Q99942

0

ubiquitination

down-regulates quantity by destabilization

0.2

E3 ubiquitin ligase Rma1 is involved in Pendrin degradation

SIGNOR-271497

Q9NYA1

Q8TD94

0

transcriptional regulation

up-regulates quantity by expression

0.2

KLF14 Is a Transcriptional Activator of SK1 Gene Expression in Endothelial Cells

SIGNOR-266047

O14936

Q02410

2

binding

up-regulates activity

0.851

Interaction with Munc18 increases Mint1 binding to CASK.

SIGNOR-264041

P08709

P00740

2

binding

up-regulates activity

0.55

TF has a high affinity for FVII and enables the trace levels (∼1% of the total FVII) of activated FVII (FVIIa) in the blood to cleave specific sites in the serine proteases FIX and FX, activating them into FIXa and FXa, respectively.

SIGNOR-263544

Q00987

Q6K0P9

2

binding

down-regulates quantity by destabilization

0.414

Here, we show that IFIXalpha1 downregulates HDM2, a principal negative regulator of p53, at the posttranslational level. IFIXalpha1 destabilizes HDM2 protein and promotes its ubiquitination. The E3 ligase activity of HDM2 appears to be required for this IFIXalpha1 effect. Importantly, HDM2 downregulation is required for the IFIXalpha1-mediated increase of p53 protein levels, transcriptional activity, and nuclear localization, suggesting that IFIXalpha1 positively regulates p53 by acting as a negative regulator of HDM2.

SIGNOR-268493

P49755

Q9Y3A6

2

binding

up-regulates activity

0.568

P28 forms hetero-oligomeric complexes with p23. p23 is a major determinant for efficient targeting of p28 to the ERGIC

SIGNOR-261298

Q14765

O60674

0

phosphorylation

up-regulates

0.676

Janus family tyrosine kinases jak2 and tyk2, which in turn phosphorylate stat4 on tyrosine 693. The p38 mitogen-activated protein kinase (mapk) signaling pathway is also activated in response to il-12, followed by phosphorylation of stat4 on serine 721, which is required for stat4 full transcriptional activity

SIGNOR-142736

Q9UHD2

K9N643

2

binding

down-regulates activity

0.2

Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε, and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm

SIGNOR-260593

P27361

P00533

1

phosphorylation

down-regulates

0.557

It is likely that the map2 and ert kinases account for the phosphorylation of the egf receptor at thr669 (egf receptor (krel veplt669psgeapnqallr)) observed in cultured cells.Phosphorylation at ser-695 is partial and occurs only if thr-693 is phosphorylated. Phosphorylation at thr-678 and thr-693 by prkd1 inhibits egf-induced mapk8/jnk1 activation.

SIGNOR-20549

P31749

O15530

0

phosphorylation

up-regulates

0.748

We have partially purified a kinase from brain extract that phosphorylates Ser473 of PKBalpha in a PtdIns(3,4,5)P3-dependent manner and that is immunoprecipitated with PDK1 antibodies.

SIGNOR-67367

Q02078

P11802

2

binding

down-regulates

0.284

In contrast to cdk2, cyclin d/cdk4 blocks myod activity through an as yet unclear mechanism that may involve direct binding. Cyclin d/cdk4 can also block the activity of myogenin and all mef2 isoforms.

SIGNOR-176515

P28482

P24928

1

phosphorylation

down-regulates

0.311

Erk1/2 are major ser-5 kinases after h2o2 treatment. These results suggest that subsequent to h2o2 treatment, the ser-5-phosphorylated form, but not the ser-2-phosphorylated form or the unphosphorylated form, is targeted for rapid proteasomal degradation through its ubiquitination.

SIGNOR-120160

Q05682

Q9UQM7

0

phosphorylation

down-regulates

0.2

Smooth muscle caldesmon was phosphorylated by smooth muscle calmodulin-dependent protein kinase. Ii

SIGNOR-22635

P14210

Q02447

0

transcriptional regulation

up-regulates quantity by expression

0.2

Furthermore, in transient cotransfection assays, overexpression of Sp1 and/or Sp3 stimulated HGF promoter activity independently and additively through binding to the Sp1 binding site in the HGF gene promoter region.

SIGNOR-251741

Q92794

Q01196

2

binding

up-regulates

0.465

The activation domain of aml1 is required for its interaction with moz / moz activates aml1_mediated transcription

SIGNOR-113056

Q08209

P53805

2

binding

down-regulates activity

0.633

MCIP proteins can bind to and inhibit calcineurin, a calcium/calmodulin-regulated serine/threonine protein phosphatase that is activated during cardiac hypertrophy and failure

SIGNOR-252025

Q92529

P04626

0

relocalization

up-regulates

0.549

Erbb3 is characterized by a large number of binding sites for phosphatidylinositol-3-kinase (pi3k), while erbb2 has only few interaction partners with shc as the most frequent one.

SIGNOR-146855

Q15654

Q12923

0

dephosphorylation

down-regulates activity

0.434

PTPL1/FAP-1 negatively regulates TRIP6 function in lysophosphatidic acid-induced cell migration.|Here we further demonstrate that a switch from c-Src-mediated phosphorylation to PTPL1/Fas-associated phosphatase-1-dependent dephosphorylation serves as an inhibitory feedback control mechanism of TRIP6 function in LPA-induced cell migration. PTPL1 dephosphorylates phosphotyrosine 55 of TRIP6 in vitro and inhibits LPA-induced tyrosine phosphorylation of TRIP6 in cells.

SIGNOR-248713

P15172

Q92831

2

binding

up-regulates

0.647

Our results provide direct evidence that myod acetylation functionally activates the protein and show that both pcaf and cbp/p300 are candidate enzymes for myod acetylation in vivo

SIGNOR-81059

Q96EP0

Q14790

0

cleavage

down-regulates activity

0.315

We show that LUBAC interacted with caspase-1 via HOIP and modified its CARD domain with linear polyubiquitin and that depletion of HOIP or Sharpin resulted in heightened caspase-1 activation and cell death in response to inflammasome activation, unlike what is observed in macrophages. Reciprocally, caspase-1, as well as caspase-8, regulated LUBAC activity by proteolytically processing HOIP at Asp-348 and Asp-387 during the execution of cell death.

SIGNOR-272194

Q9NQU5

O43426

1

phosphorylation

up-regulates activity

0.2

We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo.

SIGNOR-263022

Q9NPG1

O00744

2

binding

up-regulates

0.617

Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.

SIGNOR-131625

Q06124

Q9UJC3

2

binding

down-regulates activity

0.353

The protein-tyrosine phosphatase domain and N-terminal SH2 domain of SHP2 directly interacted with Hook1. Down-regulation of Hook1 increased SHP2 activity. These results suggested that Hook1 was an endogenous negative regulator of SHP2 phosphatase activity.

SIGNOR-260642

P23246

P49840

0

phosphorylation

down-regulates

0.2

Psf is directly phosphorylated by gsk3, thus promoting interaction of psf with trap150, which prevents psf from binding cd45 pre-mrna. / threonine phosphorylation of psf by gsk3 primarily occurs on residue t687

SIGNOR-168385

Q9H2X6

Q09472

1

phosphorylation

up-regulates activity

0.611

Furthermore, HIPK2 forms a complex with the coactivator p300 and AML1, phosphorylates p300 at multiple Serine/Threonine sites and activates p300 HAT activity and coactivator function.

SIGNOR-278943

P05164

P02647

1

oxidation

down-regulates activity

0.406

When apolipoprotein A-I (apoA-I), the major HDL protein, was oxidized by MPO, its ability to promote cellular cholesterol efflux by ABCA1 was impaired. Moreover, oxidized apoA-I was unable to activate lecithin:cholesterol acyltransferase (LCAT), which rapidly converts free cholesterol to cholesteryl ester, a critical step in HDL maturation

SIGNOR-252102

Q13185

P68431

2

binding

up-regulates activity

0.2

A core characteristic of heterochromatin is its association with heterochromatin protein 1 (HP1) proteins, a highly conserved family of chromosomal proteins that bind to di- and trimethylated H3K9 via a conserved N-terminal domain called the chromodomain (CD) HP1 proteins are a highly conserved family of eukaryotic proteins that bind to methylated histone H3 lysine 9 (H3K9) and are required for heterochromatic gene silencing.

SIGNOR-264496

Q92847

O00230

2

binding

up-regulates

0.471

In human tissues cst-14 as well as cst-17 but not ss-14 bind the gh secretagogue receptor (ghs-r).

SIGNOR-91134

P10415

P27361

0

phosphorylation

up-regulates

0.56

Erk1 and erk2 directly phosphorylate bcl2 exclusively at ser-70 p44mapk/extracellular signal-regulated kinase 1 (erk1) and p42 mapk/erk2 are activated by il-3, colocalize with mitochondrial bcl2, and can directly phosphorylate bcl2 on ser-70 in a stauro-resistant manner both in vitro and in vivo molecular association.

SIGNOR-74935

Q03113

O00254

2

binding

up-regulates activity

0.385

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257409

Q8NBJ5

P08123

1

glycosylation

up-regulates activity

0.429

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

SIGNOR-261153

P04004

P17252

0

phosphorylation

up-regulates quantity by stabilization

0.318

Phosphorylation of vitronectin on Ser362 by protein kinase C attenuates its cleavage by plasmin.

SIGNOR-248962

Q92786

Q9Y478

0

phosphorylation

down-regulates quantity by destabilization

0.2

Furthermore, the Ser79 phosphorylation of PROX1 by AMPK enhances the recruitment of CUL4-DDB1 ubiquitin ligase to promote PROX1 degradation.

SIGNOR-277609

O15554

P17612

0

phosphorylation

down-regulates activity

0.2

Mutating the single PKA site (S334A) in human KCa3.1 abolished the PKA-dependent regulation. CaM-affinity chromatography showed that CaM binding to KCa3.1 was decreased by PKA-dependent phosphorylation of S334, and this regulation was absent in the S334A mutant.The results above indicate that PKA activation led to a phosphorylation event that inhibited KCa3.1 channel activity

SIGNOR-276855

P06493

Q92993

1

phosphorylation

up-regulates

0.478

Moreover, app stabilized tip60 through cdk-dependent phosphorylation

SIGNOR-139653

P23588

Q14004

0

phosphorylation

up-regulates activity

0.251

CDK13 directly phosphorylates 4E-BP1 at Thr46 and eIF4B at Ser422; genetically or pharmacologically inhibiting CDK13 disrupts mRNA translation.

SIGNOR-273115

P54764

P52803

2

binding

up-regulates

0.945

Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor

SIGNOR-52473

P62826

O96013

0

phosphorylation

up-regulates

0.308

We show that ran is a substrate for p21-activated kinase 4 (pak4) and that its phosphorylation on serine-135 increases during mitosis.Altogether, our findings strongly suggest that pak4-mediated phosphorylation of gdp- or gtp-bound ran modulates the assembly of complexes that are required at specific subcellular localizations for ran to carry out its functions during mitotic progression.

SIGNOR-167667

P18850

Q16549

0

phosphorylation

up-regulates

0.2

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

SIGNOR-89813

O60907

P35222

2

binding

up-regulates activity

0.659

TBL1 appears to serve two roles in regulating the activity of β-catenin. Besides the initially identified role of TBL1 in recruiting β-catenin to the SCF(TBL1) complex, it has also been shown to function as a transcriptional co-activator of β-catenin in recruiting it to the promoter site of Wnt target genes. Our results indicated that TBL1 can inhibit the polyubiquitination of β-catenin by Siah-1 in vitro (Fig. 3) and stabilize β-catenin in cells by protecting it from Siah-1-mediated ubiquitination and proteasomal degradation (Fig. 4).

SIGNOR-271954

P12931

Q9NZC7

1

phosphorylation

up-regulates

0.48

The tyrosine kinase, src, phosphorylates wwox at tyrosine 33 in the first ww domain and enhances its binding to p73.

SIGNOR-123819