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
Q13153	P19086	1	phosphorylation	up-regulates	0.2	Phosphorylation of either ser(16) by pak1 or ser(27) by pkc decreased the affinity of galpha(z) for gbetagamma;phosphorylation of both residues by pkc caused no further effect. Pak1 thus regulates galpha(z) function by attenuating the inhibitory effects of both gaps and gbetagamma.	SIGNOR-48673
O15534	Q92973	0	relocalization	up-regulates activity	0.268	The non-classical nuclear import carrier Transportin 1 modulates circadian rhythms through its effect on PER1 nuclear localization	SIGNOR-262102
O15217	P0DMV9	0	relocalization	up-regulates activity	0.2	Model showing Ser189/Thr193 protein kinase dependent phosphorylation of GST A4‐4 has increased affinity for chaperone Hsp70 which activates mitochondrial competent import signals for GSTA4‐4. \|Protein kinase A mediated phosphorylation of serine residues of CYPs increases the affinity of proteins for binding to cytoplasmic chaperones such as heat shock proteins (Hsp), Hsp70/Hsp90, resulting in increased mitochondrial translocation	SIGNOR-264800
O15392	P98170	2	binding	up-regulates	0.494	Formation of a survivin-xiap complex promotes increased xiap stability against ubiquitination/proteasomal destruction and synergistic apoptosis	SIGNOR-126367
P43657	P08754	2	binding	up-regulates activity	0.2	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-256868
Q9BXM7	Q7KZI7	0	phosphorylation	up-regulates activity	0.367	MARK2 phosphorylated and activated the cleaved form of PINK1 (DeltaN-PINK1	SIGNOR-278975
P15941	P06239	0	phosphorylation	up-regulates activity	0.46	The present results demonstrate that Lck phosphorylation of MUC1 on Y-46 also increases binding of MUC1 and beta-catenin. The results further show that ZAP-70 phosphorylation of MUC1-CD stimulates the interaction of MUC1 and beta-catenin	SIGNOR-249358
P06493	Q99640	2	phosphorylation	down-regulates activity	0.752	Active Cdk1 phosphorylates and inhibits Wee1 and Myt1 kinases and phosphorylates and activates the Cdc25 phosphatases.	SIGNOR-279600
Q5S007	Q92997	2	binding	up-regulates	0.48	Subsequent assays confirmed a direct interaction between the lrrk2 roccor domain and all three human dvl proteins, these data are consistent with a role for lrrk2 in the activation of canonical wnt signaling bringing dvl proteins to cellular membranes.	SIGNOR-202187
P24941	Q8WZ60	0	polyubiquitination	down-regulates quantity by destabilization	0.2	We confirmed the formation of ubiquitin and CDK2 by different systems and further identified the E3 ligase KLHL6 as a mediator of the ubiquitination and degradation of CDK2.	SIGNOR-272310
O00327	P51449	0	transcriptional regulation	up-regulates quantity by expression	0.502	As RORs function as transcriptional activators and their expression correlates with histone acetylation and chromatin accessibility, RORs are thought to function as positive regulators of Bmal1 expression at its peak levels, whereas REV-ERBs block ROR and negatively regulate Bmal1 at the trough of its expression.	SIGNOR-268004
Q8N2W9	Q12888	1	sumoylation	up-regulates	0.637	Pias1 and pias4 are recruited to dna-damage sites and mediate 53bp1 recruitment and sumoylation	SIGNOR-162167
Q13285	Q9HAZ1	0	phosphorylation	up-regulates activity	0.2	Immunoblotting analyses showed that the phosphorylation status of NR5A1 at Ser203 was attenuated by the CLK1/4 inhibitor.	SIGNOR-274117
P19086	P50406	2	binding	up-regulates activity	0.25	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-257274
O60675	P54821	2	binding	down-regulates activity	0.273	Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.	SIGNOR-221932
P35222	Q92729	0	dephosphorylation	down-regulates activity	0.4	Protein tyrosine phosphatase receptor U (PTPRU) has been shown to be a tumor suppressor in colon cancer by dephosphorylating \u03b2-catenin and reducing the activation of \u03b2-catenin signaling.	SIGNOR-277095
P04637	Q92570	1	transcriptional regulation	up-regulates quantity by expression	0.264	We showed that p53 directly bound the promoter of NR4A3 gene and induced its transcription. p53 transactivates the NR4A3 promoter in H1299 cells.	SIGNOR-256200
Q8TB45	P35790	0	phosphorylation	down-regulates quantity by destabilization	0.2	These data suggests that CKI overexpression may overcome a requirement for phosphorylation at the major mTOR sites in DEPTOR for formation of the degron and are consistent with our finding that CKI can phosphorylate S286 and S287 in DEPTOR in vitro in the absence of mTOR.	SIGNOR-279605
O95379	P08754	2	binding	up-regulates activity	0.2	TNFAIP8: a new effector for Galpha(i) coupling to reduce cell death and induce cell transformation	SIGNOR-256490
Q6ZUJ8	P42336	2	binding	up-regulates	0.416	This accumulation of tyrosine-phosphorylated bcap at the membrane with its associated pi3k would then allow for the catalysis of ptd ins p2 to ptd ins p3 and downstream pi3k-dependent signals. Therefore, bcap is an essential activator of the pi3k pathway downstream of tlr signaling, providing a brake to limit potentially pathogenic excessive tlr responses.	SIGNOR-191664
Q02556	Q06124	0	dephosphorylation	down-regulates activity	0.353	We found that Bcr-abl-induced, Shp2 dependent dephosphorylation of Icsbp impaired repression of GAS2 by this transcription factor.	SIGNOR-277173
O60664	P51151	0	null	up-regulates activity	0.591	Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector	SIGNOR-253089
P35790	Q00987	1	phosphorylation	down-regulates quantity by destabilization	0.274	The data presented here provides evidence for a molecular mechanism by which CKI-dependent phosphorylation of Mdm2 at multiple sites triggers SCF \u03b2-TRCP -mediated Mdm2 destruction ( xref ).	SIGNOR-279606
Q13315	Q9BUR4	1	phosphorylation	up-regulates activity	0.337	Here, we show that in response to various types of DNA damage, including IR and UV, WRAP53β is phosphorylated on serine residue 64 by ATM with a time-course that parallels its accumulation at DNA lesions. Interestingly, recruitment of phosphorylated WRAP53β (pWRAP53βS64) to sites of such DNA damage promotes its interaction with γH2AX at these locations.	SIGNOR-273511
P22888	P01229	2	binding	up-regulates	0.684	Hcg is a heterodimeric glycoprotein hormone, consisting of a common? -subunit and a hormone-specific ?-Subunit (2). It binds to the lh receptor (lhr).	SIGNOR-70028
Q01082	P68400	0	phosphorylation	down-regulates	0.334	We show here that the short c-terminal splice variant of betaii-spectrin (betaiisigma2) is a substrate for phosphorylation. In vitro, protein kinase ck2 phosphorylates ser-2110 and thr-2159 / phosphorylation of ?II?2 C-terminal fragment inhibits its interaction with ?II N-terminal fragment.	SIGNOR-150471
O96019	P50750	0	phosphorylation	up-regulates activity	0.323	Collectively, these results suggest that the cdk9 and Cyclin T complex more efficiently phosphorylates Baf53 in vitro.	SIGNOR-279689
P19784	Q14005	1	phosphorylation	up-regulates activity	0.326	We now show that N-terminal to the NLS domain of pro-IL-16 are protein kinase CK2 substrate and cdc2 kinase substrate sites which, along with the NLS, constitute a dual phosphorylation-regulated CcN motif which regulates nuclear localization of pro-IL-16. In addition, we demonstrate that mutation of either site is associated with impairment of the N-terminal domain's ability to induce G(0)/G(1) cell cycle arrest. \| Thus, we confirm that the N-terminal (42SLNEE46) sequence of pro-IL-16 is in fact a site for protein kinase CK2 phosphorylation.	SIGNOR-251009
O96017	P67775	0	dephosphorylation	up-regulates activity	0.432	Protein phosphatase 2A interacts with Chk2 and regulates phosphorylation at Thr-68 after cisplatin treatment of human ovarian cancer cells\|In response to DNA damage, Chk2 is initially phosphorylated at Thr-68, which leads to its full activation.	SIGNOR-248617
P83916	Q7Z589	2	binding	up-regulates activity	0.2	The binding sites for HP1β and BS69 with EMSY abut each other, and are found directly adjacent to the ENT domain of EMSY. This demonstrates that EMSY has the capacity to contact directly at least two proteins which contain a Royal Family domain. Since this domain is found in proteins with a chromatin connection, we assume that EMSY functions, at least partly, in the regulation of chromatin.	SIGNOR-263917
O60858	P22736	1	ubiquitination	down-regulates quantity by destabilization	0.2	These results suggest that Trim13 activity mediates Nur77 ubiquitination, leading to its degradation.	SIGNOR-278564
Q99705	P50148	2	binding	up-regulates activity	0.529	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-257302
Q9BX63	P38398	2	binding	up-regulates activity	0.796	BRCA1 interacts in vivo with a novel protein, BACH1, a member of the DEAH helicase family. BACH1 binds directly to the BRCT repeats of BRCA1. Moreover, BACH1 likely contributes to the DNA repair function of BRCA1 [].	SIGNOR-259185
O14795	Q9UJD0	0	relocalization	up-regulates activity	0.266	N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle	SIGNOR-264384
Q8N5S9	P0DP24	2	binding	up-regulates	0.488	The binding of Ca2+/CaM to CaM-KK is absolutely required for its activation and efficient phosphorylation of target protein kinases	SIGNOR-266328
Q8IWV1	P43405	0	phosphorylation	up-regulates activity	0.378	Upon stimulation via the B or T cell receptors, LAX is rapidly phosphorylated by Src and Syk family tyrosine kinases and interacts with Grb2, Gads, and p85.	SIGNOR-273535
P30304	P14635	1	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
P35372	P08754	2	binding	up-regulates activity	0.513	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-256854
O00141	Q92542	1	phosphorylation	down-regulates quantity	0.337	Furthermore, SGK1 directly bound to and phosphorylated Nicastrin on Ser437, thereby promoting protein degradation.\|We showed that SGK1 downregulates Nicastrin protein levels.	SIGNOR-280122
P61812	P37173	2	binding	up-regulates	0.754	We show that tbetarii-b, an alternatively spliced variant of the tgf-beta type ii receptor, is a tgf-beta2 binding receptor, which mediates signalling via the smad pathway in the absence of any tgf-beta type iii receptor	SIGNOR-104795
P14618	P30304	0	dephosphorylation	up-regulates activity	0.487	Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2 dependent beta-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop.\|Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2-dependent \u03b2-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop.	SIGNOR-276967
Q14164	Q14653	1	phosphorylation	up-regulates activity	0.741	Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404.	SIGNOR-178379
Q09472	Q92585	2	acetylation	up-regulates	0.651	The n-terminal domain of maml1 directly interacts with both p300 and histones, and the p300-maml1 complex specifically acetylates histone h3 and h4 tails in chromatin. Furthermore, p300 acetylates maml1 and evolutionarily conserved lysine residues in the maml1 n-terminus are direct substrates for p300-mediated acetylation.	SIGNOR-153035
P14136	P17612	0	phosphorylation	down-regulates activity	0.283	GFAP can serve as a substrate for phosphorylation by CAMP-dependent protein kinase. CAMP-dependent protein kinase or protein kinase C phosphorylated Ser-8, Ser-13, and Ser-34.each phosphorylation was shown to induce disassembly of the glial filaments.	SIGNOR-249713
P04628	Q9NPG1	2	binding	up-regulates activity	0.628	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-131571
P49841	Q9BPU6	1	phosphorylation	up-regulates activity	0.431	The T516 phosphorylation was achieved by the glycogen synthase kinase-3beta (GSK-3beta), which can phosphorylate the wildtype protein but not the non-phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin-binding property of CRMP5. Therefore, CRMP5-induced growth inhibition is dependent on T516 phosphorylation through the GSK-3beta pathway.	SIGNOR-264835
P62140	P42575	1	dephosphorylation	up-regulates activity	0.2	Nutrient-replete oocytes inhibit C2 via S135 phosphorylation catalyzed by calcium/calmodulin-dependent protein kinase II. We now show that C2 phosphorylated at S135 binds 14-3-3zeta, thus preventing C2 dephosphorylation. Moreover, we determined that S135 dephosphorylation is catalyzed by protein phosphatase-1 (PP1), which directly binds C2.	SIGNOR-248576
P59768	P62873	2	binding	up-regulates activity	0.94	GNG2 dissociates from the activated receptor, bound with GNB1 as stable dimer.	SIGNOR-251106
P06400	Q01094	2	binding	down-regulates activity	0.921	E2f binds rb. E2f activation domain is the target for rb-induced repression. Rb can silence the 57 residue e2f activation domain. Rb can mask e2f residues involved in the activation process, possibly by mimicking a component of the transcriptional machinery	SIGNOR-37305
P04637	O43474	0	transcriptional regulation	down-regulates quantity by repression	0.56	Previous work has shown that the Kruppel-like factor 4 (KLF4) transcription factor represses p53 transcription by binding to the PE21 element.	SIGNOR-270544
Q8WXE1	P24941	0	phosphorylation	up-regulates	0.579	Atrip is a cdk2 substrate, and cdk2-dependent phosphorylation of s224 regulates the ability of atr-atrip to promote cell cycle arrest in response to dna damage./ One possibility is s224 phosphorylation creates a binding site for another protein involved in the g2-m checkpoint response	SIGNOR-156928
P05787	Q16539	0	phosphorylation	up-regulates	0.592	Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif ((68)nqsllspl) and becomes phosphorylated in cultured cells and organs during mitosis, cell stress, and apoptosis. Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase.The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis.	SIGNOR-114079
P31749	Q15672	1	phosphorylation	up-regulates	0.438	Moreover, phosphorylation of twist-1 at ser42 was shown in vivo in various human cancer tissues, suggesting that this post-translational modification ensures functional activation of twist-1 after promotion of survival during carcinogenesis.	SIGNOR-164884
O14641	P48730	0	phosphorylation	up-regulates	0.534	Ck1_/__dependent phosphorylation of dvl2 at s143 and t224and that this event is critical to interact with plk1 in early stages of the cell cycle	SIGNOR-197547
O43791	O75496	1	ubiquitination	down-regulates activity	0.2	SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. This poly-ubiquitination of Geminin prevents DNA replication over-firing by indirectly blocking the association of Cdt1 with the MCM protein complex, an interaction required for DNA unwinding and replication.	SIGNOR-268926
Q16816	P06737	1	phosphorylation	up-regulates activity	0.54	It is well-characterized that GP is activated by PhK-mediated serine phosphorylation at Ser-15	SIGNOR-267399
P04626	P03372	1	phosphorylation	up-regulates	0.572	The results presented here show for the first time that er redistribution to the cytoplasm and its interaction with her2 are important downstream effects of her2 overexpression, that erk1/2 is important for er cytoplasmic localization, and that subcellular localization of er may play a mechanistic role in determining the responsiveness of breast cancer cells to tamoxifen.	SIGNOR-124962
P51812	Q9Y4K3	1	phosphorylation	up-regulates activity	0.272	These results demonstrate that TRAF6 K63 ubiquitination might be regulated by an RSK2 mediated phosphorylation dependent mechanism and phosphorylation of TRAF6 at Ser46, 47 and 48 enhances its ubiquitin mediated inflammation signaling.	SIGNOR-278302
P31749	P12268	1	phosphorylation	up-regulates activity	0.386	Further, we have demonstrated an in vivo association of IMPDH and PKB/Akt by co‐immunoprecipitation from COS cells expressing a constitutively active form of PKB/Akt. Finally, we were able to show that this constitutively active PKB/Akt could phosphorylate IMPDH in vitro. Thus, the interplay between PKB/Akt and IMPDH reported here could suggest that PKB/Akt activation leads to IMPDH type II activation which in turn prepares the cell for entry into S phase.	SIGNOR-261262
P49336	P46531	1	phosphorylation	down-regulates	0.552	Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo.	SIGNOR-130640
P05107	Q05655	0	phosphorylation	up-regulates	0.329	In this study, we present evidence that pkc isoforms are the major protein kinases that phosphorylate the c terminus of the integrin cd18 chain in leukocytes. Ser-745 is identified as a novel phosphorylation site in the integrin cytoplasmic domain. Additionally, we show that a thr-758-phosphorylated integrin peptide can interact with 14-3-3 proteins in leukocyte lysates	SIGNOR-178897
Q92673	P02649	2	binding	up-regulates	0.62	Lr11 binds the apolipoprotein e (apoe)-rich lipoproteins, beta-very low density lipoproteins (vldls), with a high affinity similar to that of other members, such as the ldlr and vldl receptor.Incubation For 48 hours with beta-vldl of lr11-overexpressing cells, but not of control cells, promotes the appearance of numerous intracellular lipid droplets.	SIGNOR-110555
P63096	P30556	2	binding	up-regulates activity	0.25	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-256738
P29350	P12931	2	dephosphorylation	up-regulates activity	0.527	Several protein tyrosine phosphatases are capable of activating Src by dephosphorylating Y530 (reviewed in ref. 9). These include PTP-α, PTP-λ, SHP-1, SHP-2, and PTP1B	SIGNOR-248472
P05771	P04049	1	phosphorylation	up-regulates	0.445	Pkc can effectively phosphorylate raf-1, this is a direct effect of activated pkc and not the result of raf-1 autophosphorylation. the sites of pkc-mediated raf-1 phosphorylation are deduced to be ser497 and ser619.	SIGNOR-37474
P56211	Q96GX5	0	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
Q8TDC3	P23258	1	phosphorylation	up-regulates	0.248	Sadb kinases associate and phosphorylate gamma-tubulin on ser 131 s131d gamma-tubulin expression amplifies centrosome duplication	SIGNOR-187405
P30405	P49841	0	phosphorylation	up-regulates activity	0.378	Phosphorylation of cyclophilin D at serine 191 regulates mitochondrial permeability transition pore opening and cell death after ischemia-reperfusion\|We conclude that CypD phosphorylation at S191 residue leads to its binding to OSCP and thus sensitizes mPTP opening for the subsequent cell death.\|Under baseline condition (WT group), the phosphorylation of CypD by a kinase (e.g. GSK3beta) at S191 induces its translocation to the OSCP, to favor mPTP opening and subsequent cell death at reperfusion.	SIGNOR-264880
P01106	Q8N699	1	transcriptional regulation	up-regulates quantity by expression	0.298	MT-MC1 is a widely expressed nuclear protein whose overexpression, unlike that of c-Myc targets reported previously, recapitulates multiple c-Myc phenotypes. These include promotion of apoptosis, alteration of morphology, enhancement of anchorage-independent growth, tumorigenic conversion, promotion of genomic instability, and inhibition of hematopoietic differentiation. The MT-MC1 promoter is a direct c-Myc target; it contains two consensus E-box elements, both of which bind c-Myc.	SIGNOR-261736
Q06945	O00560	2	binding	up-regulates activity	0.538	Sox4 activation by IL-5R_ appears to be direct, with syntenin functioning as an adaptor molecule. Syntenin mediates IL-5induced Sox4 activation.	SIGNOR-223089
P63000	P15498	0	guanine nucleotide exchange factor	up-regulates activity	0.765	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-260581
Q16539	P03372	1	phosphorylation	up-regulates	0.625	Conversely, constitutively active mkk6 induced p38 mapk activation that recapitulated the effects of polyphenols by inducing eralpha phosphorylation and downstream activation of akt, and enos. The key role of eralpha ser-118 phosphorylation was confirmed in enos-transfected cos-7 cells	SIGNOR-136950
P35222	P55285	2	binding	up-regulates activity	0.578	At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin	SIGNOR-265868
P50148	Q99677	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-257383
P08238	Q8TF40	2	binding	down-regulates activity	0.2	FNIP1 and FNIP2 facilitate FLCN binding to Hsp90 chaperone. Our results suggest that FNIP1 is a potent inhibitor of Hsp90 ATPase activity, as 200 nM of FNIP1 inhibits Hsp90 ATPase activity by 50-fold. FNIP2 also has shown inhibitory activity towards Hsp90; however, it required 1.6 μM of FNIP2 to inhibit the ATPase activity by eightfold. Although we use the term ‘inhibition' here, FNIPs seem only to be slowing the chaperone cycle.	SIGNOR-261415
P38405	P32239	2	binding	up-regulates activity	0.265	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-256908
Q13131	Q6N021	1	phosphorylation	up-regulates quantity by stabilization	0.2	We identify the tumour suppressor TET2 as a substrate of the AMP-activated kinase (AMPK), which phosphorylates TET2 at serine 99, thereby stabilizing the tumour suppressor. Increased glucose levels impede AMPK-mediated phosphorylation at serine 99, which results in the destabilization of TET2 followed by dysregulation of both 5-hydroxymethylcytosine (5hmC) and the tumour suppressive function of TET2 in vitro and in vivo	SIGNOR-256134
A6ND36	P48729	2	binding	up-regulates quantity	0.373	We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.	SIGNOR-273745
P00738	Q9NZP8	0	cleavage	up-regulates activity	0.375	We demonstrate that coexpression of the proform of Hp (proHp) and C1r-LP in COS-1 cells effected cleavage of proHp in the endoplasmic reticulum. This cleavage depended on proteolytic activity of C1r-LP because mutation of the putative active-site Ser residue abolished the reaction. Furthermore, incubation of affinity-purified C1r-LP and proHp led to the cleavage of the latter protein. ProHp appeared to be cleaved at the expected site because substitution of Gly for Arg-161 blocked the reaction.	SIGNOR-256358
Q96LB2	P50148	2	binding	up-regulates activity	0.342	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-257384
P07195	O14965	0	phosphorylation	up-regulates activity	0.2	Aurora-A-mediated phosphorylation of LDHB serine 162 significantly increases its activity in reducing pyruvate to lactate, which efficiently promotes NAD+ regeneration, glycolytic flux, lactate production and bio-synthesis with glycolytic intermediates.	SIGNOR-277493
P24723	Q15139	1	phosphorylation	up-regulates	0.355	These results provide direct evidence that pkd becomes activated in vivo as a consequence of pkc-mediated phosphorylation of serines 744 and 748.	SIGNOR-66734
P08754	P48039	2	binding	up-regulates activity	0.498	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-256849
P12931	Q9Y2X7	1	phosphorylation	up-regulates activity	0.542	Tyrosines 246 and 293 are required to hold GIT1 in a closed conformation.Hyperphosphorylation of GIT1-N by Src and pervanadate does not affect its binding in vitro to full length GIT1 proteins. Mutations Y246E and Y293E of GIT1 enhance binding to paxillin.	SIGNOR-276627
P35568	Q15418	0	phosphorylation	down-regulates quantity by destabilization	0.358	Negative feedback involves s6k, which inactivates irs by phosphorylation at multiple sites, thus inducing its degradation and altered cell localization.	SIGNOR-175687
P12931	P52789	1	phosphorylation	up-regulates activity	0.362	Here we find that c-Src can interact with and phosphorylate hexokinases HK1 and HK2, the rate limiting enzymes in glycolysis.\|Moreover, c-Src could efficiently stimulate the catalytic activities of HK1 and HK2, but failed to stimulate their corresponding mutants (XREF_FIG and XREF_SUPPLEMENTARY).	SIGNOR-278499
P23458	Q8NI17	2	binding	up-regulates	0.497	Il-31 can activate janus kinase (jak) 1 and jak2 signaling molecules after binding to its receptor complex.	SIGNOR-161342
Q2M2I8	Q96CW1	1	phosphorylation	up-regulates	0.79	Aak1 is enriched at presynaptic terminals, whereas in nonneuronal cells it colocalizes with clathrin and ap2 in clathrin-coated pits and at the leading edge of migrating cells. Aak1 specifically phosphorylates the mu subunit in vitro, and stage-specific assays for endocytosis show that mu phosphorylation by aak1 results in a decrease in ap2-stimulated transferrin internalization. Together, these results provide strong evidence that aak1 is the endogenous mu 2 kinase and plays a regulatory role in clathrin-mediated endocytosis.	SIGNOR-115657
Q9UNW8	P19086	2	binding	up-regulates activity	0.2	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-257275
P10451	P15036	0	transcriptional regulation	up-regulates quantity by expression	0.251	We demonstrated that Ets2 is capable of binding to and transactivating the OPN promoter using gel shift and transient transfection assays	SIGNOR-259872
P08754	P28223	2	binding	up-regulates activity	0.268	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-256885
O96013	Q16236	1	phosphorylation	down-regulates quantity by destabilization	0.2	PAK4 directly phosphorylated Nrf2 at T369, and it led to its nuclear export and proteasomal degradation, all of which impaired antioxidant responses in hepatocytes.	SIGNOR-277583
P05412	P17947	2	binding	up-regulates activity	0.555	These results indicate that AML1-ETO competes c-Jun away from binding to the β3β4 domain of PU.1. Thus, the c-Jun coactivation function of PU.1 is down-regulated and this in turn down-regulates transcriptional activity of PU.1.	SIGNOR-255660
P01042	P03952	0	cleavage	up-regulates activity	0.779	Bradykinin is a nonapeptide composed of the sequence Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg and functions as an inflammatory mediator. BK is the product of the kallikrein–kinin system following activation of FXII. FXIIa leads to proteolysis of PK, and the resulting PKa cleaves HK to generate BK (Figure 1).	SIGNOR-263548
P07101	P51812	0	phosphorylation	up-regulates	0.267	Mitogen-activated protein-kinase (map) kinase-activated protein kinases 1 and 2 (mapkap kinase-1, mapkap kinase-2), were found to phosphorylate bacterially expressed human tyrosine hydroxylaserecombinant human tyrosine hydroxylase (hth1) was found to be phosphorylated by mitogen and stress-activated protein kinase 1 (msk1) at ser40 and by p38 regulated/activated kinase (prak) on ser19. Phosphorylation by msk1 induced an increase in vmax	SIGNOR-34682
P43034	Q8WVJ2	2	binding	up-regulates quantity by stabilization	0.44	The type I lissencephaly gene product LIS1, a key regulator of cytoplasmic dynein, is critical for cell proliferation, survival, and neuronal migration. However, little is known about the regulation of LIS1. Here, we identify a previously uncharacterized mammalian homolog of Aspergillus NudC, NudCL2 (NudC-like protein 2), as a regulator of LIS1. NudCL2 is localized to the centrosome in interphase, and spindle poles and kinetochores during mitosis, a pattern similar to the localization of LIS1 and cytoplasmic dynein. Depletion of NudCL2 destabilized LIS1 and led to phenotypes resembling those of either dynein or LIS1 deficiency. NudCL2 complexed with and enhanced the interaction between LIS1 and Hsp90. Either disruption of the LIS1-Hsp90 interaction with the C terminus of NudCL2 or inhibition of Hsp90 chaperone function by geldanamycin decreased LIS1 stability.	SIGNOR-252167
P10721	Q06124	1	phosphorylation	up-regulates activity	0.684	SHP2 can be phosphorylated at 2 C-terminal tyrosyl residues by receptor tyrosine kinases, including KIT as well as cytosolic tyrosine kinases, including Src and Abl. The level of tyrosyl phosphorylation of SHP2 has been associated with its recruitment to the receptor.Thus, pharmacologic inhibition of SHP2 phosphatase function might permit SHP2 to return to its inactive conformation resulting in reduced tyrosine phosphorylation.	SIGNOR-256140
Q969H4	P54762	2	binding	up-regulates activity	0.293	The phosphorylated CNK1 interacts with ephrinB1. The binding of ephrinB1 to CNK1 connects RhoA and p115RhoGEF with ephrinB1-associated MKK4, promoting JNK activation and cell migration.	SIGNOR-275921
P05412	P01100	2	binding	up-regulates activity	0.953	The cFos proto-oncoprotein associates with cJun to form a heterodimer with increased DNA binding and transcriptional activities.	SIGNOR-252087
P08651	Q9HCE7	0	ubiquitination	down-regulates quantity	0.329	In addition, Smurf1 knockdown also blocked the degradation of endogenous NFI-C in response to TGF-beta1 (XREF_FIG).\|In particular, Smurf1 and Smurf2 markedly increased the polyubiquitination of NFI-C in the presence of TGF-beta1 (XREF_FIG and XREF_SUPPLEMENTARY).	SIGNOR-278753

Q13153

P19086

1

phosphorylation

up-regulates

0.2

Phosphorylation of either ser(16) by pak1 or ser(27) by pkc decreased the affinity of galpha(z) for gbetagamma;phosphorylation of both residues by pkc caused no further effect. Pak1 thus regulates galpha(z) function by attenuating the inhibitory effects of both gaps and gbetagamma.

SIGNOR-48673

O15534

Q92973

0

relocalization

up-regulates activity

0.268

The non-classical nuclear import carrier Transportin 1 modulates circadian rhythms through its effect on PER1 nuclear localization

SIGNOR-262102

O15217

P0DMV9

0

relocalization

up-regulates activity

0.2

Model showing Ser189/Thr193 protein kinase dependent phosphorylation of GST A4‐4 has increased affinity for chaperone Hsp70 which activates mitochondrial competent import signals for GSTA4‐4. |Protein kinase A mediated phosphorylation of serine residues of CYPs increases the affinity of proteins for binding to cytoplasmic chaperones such as heat shock proteins (Hsp), Hsp70/Hsp90, resulting in increased mitochondrial translocation

SIGNOR-264800

O15392

P98170

2

binding

up-regulates

0.494

Formation of a survivin-xiap complex promotes increased xiap stability against ubiquitination/proteasomal destruction and synergistic apoptosis

SIGNOR-126367

P43657

P08754

2

binding

up-regulates activity

0.2

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-256868

Q9BXM7

Q7KZI7

0

phosphorylation

up-regulates activity

0.367

MARK2 phosphorylated and activated the cleaved form of PINK1 (DeltaN-PINK1

SIGNOR-278975

P15941

P06239

0

phosphorylation

up-regulates activity

0.46

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

SIGNOR-249358

P06493

Q99640

2

phosphorylation

down-regulates activity

0.752

Active Cdk1 phosphorylates and inhibits Wee1 and Myt1 kinases and phosphorylates and activates the Cdc25 phosphatases.

SIGNOR-279600

Q5S007

Q92997

2

binding

up-regulates

0.48

Subsequent assays confirmed a direct interaction between the lrrk2 roccor domain and all three human dvl proteins, these data are consistent with a role for lrrk2 in the activation of canonical wnt signaling bringing dvl proteins to cellular membranes.

SIGNOR-202187

P24941

Q8WZ60

0

polyubiquitination

down-regulates quantity by destabilization

0.2

We confirmed the formation of ubiquitin and CDK2 by different systems and further identified the E3 ligase KLHL6 as a mediator of the ubiquitination and degradation of CDK2.

SIGNOR-272310

O00327

P51449

0

transcriptional regulation

up-regulates quantity by expression

0.502

As RORs function as transcriptional activators and their expression correlates with histone acetylation and chromatin accessibility, RORs are thought to function as positive regulators of Bmal1 expression at its peak levels, whereas REV-ERBs block ROR and negatively regulate Bmal1 at the trough of its expression.

SIGNOR-268004

Q8N2W9

Q12888

1

sumoylation

up-regulates

0.637

Pias1 and pias4 are recruited to dna-damage sites and mediate 53bp1 recruitment and sumoylation

SIGNOR-162167

Q13285

Q9HAZ1

0

phosphorylation

up-regulates activity

0.2

Immunoblotting analyses showed that the phosphorylation status of NR5A1 at Ser203 was attenuated by the CLK1/4 inhibitor.

SIGNOR-274117

P19086

P50406

2

binding

up-regulates activity

0.25

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-257274

O60675

P54821

2

binding

down-regulates activity

0.273

Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.

SIGNOR-221932

P35222

Q92729

0

dephosphorylation

down-regulates activity

0.4

Protein tyrosine phosphatase receptor U (PTPRU) has been shown to be a tumor suppressor in colon cancer by dephosphorylating \u03b2-catenin and reducing the activation of \u03b2-catenin signaling.

SIGNOR-277095

P04637

Q92570

1

transcriptional regulation

up-regulates quantity by expression

0.264

We showed that p53 directly bound the promoter of NR4A3 gene and induced its transcription. p53 transactivates the NR4A3 promoter in H1299 cells.

SIGNOR-256200

Q8TB45

P35790

0

phosphorylation

down-regulates quantity by destabilization

0.2

These data suggests that CKI overexpression may overcome a requirement for phosphorylation at the major mTOR sites in DEPTOR for formation of the degron and are consistent with our finding that CKI can phosphorylate S286 and S287 in DEPTOR in vitro in the absence of mTOR.

SIGNOR-279605

O95379

P08754

2

binding

up-regulates activity

0.2

TNFAIP8: a new effector for Galpha(i) coupling to reduce cell death and induce cell transformation

SIGNOR-256490

Q6ZUJ8

P42336

2

binding

up-regulates

0.416

This accumulation of tyrosine-phosphorylated bcap at the membrane with its associated pi3k would then allow for the catalysis of ptd ins p2 to ptd ins p3 and downstream pi3k-dependent signals. Therefore, bcap is an essential activator of the pi3k pathway downstream of tlr signaling, providing a brake to limit potentially pathogenic excessive tlr responses.

SIGNOR-191664

Q02556

Q06124

0

dephosphorylation

down-regulates activity

0.353

We found that Bcr-abl-induced, Shp2 dependent dephosphorylation of Icsbp impaired repression of GAS2 by this transcription factor.

SIGNOR-277173

O60664

P51151

0

null

up-regulates activity

0.591

Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector

SIGNOR-253089

P35790

Q00987

1

phosphorylation

down-regulates quantity by destabilization

0.274

The data presented here provides evidence for a molecular mechanism by which CKI-dependent phosphorylation of Mdm2 at multiple sites triggers SCF \u03b2-TRCP -mediated Mdm2 destruction ( xref ).

SIGNOR-279606

Q13315

Q9BUR4

1

phosphorylation

up-regulates activity

0.337

Here, we show that in response to various types of DNA damage, including IR and UV, WRAP53β is phosphorylated on serine residue 64 by ATM with a time-course that parallels its accumulation at DNA lesions. Interestingly, recruitment of phosphorylated WRAP53β (pWRAP53βS64) to sites of such DNA damage promotes its interaction with γH2AX at these locations.

SIGNOR-273511

P22888

P01229

2

binding

up-regulates

0.684

Hcg is a heterodimeric glycoprotein hormone, consisting of a common? -subunit and a hormone-specific ?-Subunit (2). It binds to the lh receptor (lhr).

SIGNOR-70028

Q01082

P68400

0

phosphorylation

down-regulates

0.334

We show here that the short c-terminal splice variant of betaii-spectrin (betaiisigma2) is a substrate for phosphorylation. In vitro, protein kinase ck2 phosphorylates ser-2110 and thr-2159 / phosphorylation of ?II?2 C-terminal fragment inhibits its interaction with ?II N-terminal fragment.

SIGNOR-150471

O96019

P50750

0

phosphorylation

up-regulates activity

0.323

Collectively, these results suggest that the cdk9 and Cyclin T complex more efficiently phosphorylates Baf53 in vitro.

SIGNOR-279689

P19784

Q14005

1

phosphorylation

up-regulates activity

0.326

We now show that N-terminal to the NLS domain of pro-IL-16 are protein kinase CK2 substrate and cdc2 kinase substrate sites which, along with the NLS, constitute a dual phosphorylation-regulated CcN motif which regulates nuclear localization of pro-IL-16. In addition, we demonstrate that mutation of either site is associated with impairment of the N-terminal domain's ability to induce G(0)/G(1) cell cycle arrest. | Thus, we confirm that the N-terminal (42SLNEE46) sequence of pro-IL-16 is in fact a site for protein kinase CK2 phosphorylation.

SIGNOR-251009

O96017

P67775

0

dephosphorylation

up-regulates activity

0.432

Protein phosphatase 2A interacts with Chk2 and regulates phosphorylation at Thr-68 after cisplatin treatment of human ovarian cancer cells|In response to DNA damage, Chk2 is initially phosphorylated at Thr-68, which leads to its full activation.

SIGNOR-248617

P83916

Q7Z589

2

binding

up-regulates activity

0.2

The binding sites for HP1β and BS69 with EMSY abut each other, and are found directly adjacent to the ENT domain of EMSY. This demonstrates that EMSY has the capacity to contact directly at least two proteins which contain a Royal Family domain. Since this domain is found in proteins with a chromatin connection, we assume that EMSY functions, at least partly, in the regulation of chromatin.

SIGNOR-263917

O60858

P22736

1

ubiquitination

down-regulates quantity by destabilization

0.2

These results suggest that Trim13 activity mediates Nur77 ubiquitination, leading to its degradation.

SIGNOR-278564

Q99705

P50148

2

binding

up-regulates activity

0.529

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-257302

Q9BX63

P38398

2

binding

up-regulates activity

0.796

BRCA1 interacts in vivo with a novel protein, BACH1, a member of the DEAH helicase family. BACH1 binds directly to the BRCT repeats of BRCA1. Moreover, BACH1 likely contributes to the DNA repair function of BRCA1 [].

SIGNOR-259185

O14795

Q9UJD0

0

relocalization

up-regulates activity

0.266

N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle

SIGNOR-264384

Q8N5S9

P0DP24

2

binding

up-regulates

0.488

The binding of Ca2+/CaM to CaM-KK is absolutely required for its activation and efficient phosphorylation of target protein kinases

SIGNOR-266328

Q8IWV1

P43405

0

phosphorylation

up-regulates activity

0.378

Upon stimulation via the B or T cell receptors, LAX is rapidly phosphorylated by Src and Syk family tyrosine kinases and interacts with Grb2, Gads, and p85.

SIGNOR-273535

P30304

P14635

1

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

P35372

P08754

2

binding

up-regulates activity

0.513

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-256854

O00141

Q92542

1

phosphorylation

down-regulates quantity

0.337

Furthermore, SGK1 directly bound to and phosphorylated Nicastrin on Ser437, thereby promoting protein degradation.|We showed that SGK1 downregulates Nicastrin protein levels.

SIGNOR-280122

P61812

P37173

2

binding

up-regulates

0.754

We show that tbetarii-b, an alternatively spliced variant of the tgf-beta type ii receptor, is a tgf-beta2 binding receptor, which mediates signalling via the smad pathway in the absence of any tgf-beta type iii receptor

SIGNOR-104795

P14618

P30304

0

dephosphorylation

up-regulates activity

0.487

Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2 dependent beta-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop.|Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2-dependent \u03b2-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop.

SIGNOR-276967

Q14164

Q14653

1

phosphorylation

up-regulates activity

0.741

Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404.

SIGNOR-178379

Q09472

Q92585

2

acetylation

up-regulates

0.651

The n-terminal domain of maml1 directly interacts with both p300 and histones, and the p300-maml1 complex specifically acetylates histone h3 and h4 tails in chromatin. Furthermore, p300 acetylates maml1 and evolutionarily conserved lysine residues in the maml1 n-terminus are direct substrates for p300-mediated acetylation.

SIGNOR-153035

P14136

P17612

0

phosphorylation

down-regulates activity

0.283

GFAP can serve as a substrate for phosphorylation by CAMP-dependent protein kinase. CAMP-dependent protein kinase or protein kinase C phosphorylated Ser-8, Ser-13, and Ser-34.each phosphorylation was shown to induce disassembly of the glial filaments.

SIGNOR-249713

P04628

Q9NPG1

2

binding

up-regulates activity

0.628

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-131571

P49841

Q9BPU6

1

phosphorylation

up-regulates activity

0.431

The T516 phosphorylation was achieved by the glycogen synthase kinase-3beta (GSK-3beta), which can phosphorylate the wildtype protein but not the non-phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin-binding property of CRMP5. Therefore, CRMP5-induced growth inhibition is dependent on T516 phosphorylation through the GSK-3beta pathway.

SIGNOR-264835

P62140

P42575

1

dephosphorylation

up-regulates activity

0.2

Nutrient-replete oocytes inhibit C2 via S135 phosphorylation catalyzed by calcium/calmodulin-dependent protein kinase II. We now show that C2 phosphorylated at S135 binds 14-3-3zeta, thus preventing C2 dephosphorylation. Moreover, we determined that S135 dephosphorylation is catalyzed by protein phosphatase-1 (PP1), which directly binds C2.

SIGNOR-248576

P59768

P62873

2

binding

up-regulates activity

0.94

GNG2 dissociates from the activated receptor, bound with GNB1 as stable dimer.

SIGNOR-251106

P06400

Q01094

2

binding

down-regulates activity

0.921

E2f binds rb. E2f activation domain is the target for rb-induced repression. Rb can silence the 57 residue e2f activation domain. Rb can mask e2f residues involved in the activation process, possibly by mimicking a component of the transcriptional machinery

SIGNOR-37305

P04637

O43474

0

transcriptional regulation

down-regulates quantity by repression

0.56

Previous work has shown that the Kruppel-like factor 4 (KLF4) transcription factor represses p53 transcription by binding to the PE21 element.

SIGNOR-270544

Q8WXE1

P24941

0

phosphorylation

up-regulates

0.579

Atrip is a cdk2 substrate, and cdk2-dependent phosphorylation of s224 regulates the ability of atr-atrip to promote cell cycle arrest in response to dna damage./ One possibility is s224 phosphorylation creates a binding site for another protein involved in the g2-m checkpoint response

SIGNOR-156928

P05787

Q16539

0

phosphorylation

up-regulates

0.592

Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif ((68)nqsllspl) and becomes phosphorylated in cultured cells and organs during mitosis, cell stress, and apoptosis. Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase.The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis.

SIGNOR-114079

P31749

Q15672

1

phosphorylation

up-regulates

0.438

Moreover, phosphorylation of twist-1 at ser42 was shown in vivo in various human cancer tissues, suggesting that this post-translational modification ensures functional activation of twist-1 after promotion of survival during carcinogenesis.

SIGNOR-164884

O14641

P48730

0

phosphorylation

up-regulates

0.534

Ck1_/__dependent phosphorylation of dvl2 at s143 and t224and that this event is critical to interact with plk1 in early stages of the cell cycle

SIGNOR-197547

O43791

O75496

1

ubiquitination

down-regulates activity

0.2

SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. This poly-ubiquitination of Geminin prevents DNA replication over-firing by indirectly blocking the association of Cdt1 with the MCM protein complex, an interaction required for DNA unwinding and replication.

SIGNOR-268926

Q16816

P06737

1

phosphorylation

up-regulates activity

0.54

It is well-characterized that GP is activated by PhK-mediated serine phosphorylation at Ser-15

SIGNOR-267399

P04626

P03372

1

phosphorylation

up-regulates

0.572

The results presented here show for the first time that er redistribution to the cytoplasm and its interaction with her2 are important downstream effects of her2 overexpression, that erk1/2 is important for er cytoplasmic localization, and that subcellular localization of er may play a mechanistic role in determining the responsiveness of breast cancer cells to tamoxifen.

SIGNOR-124962

P51812

Q9Y4K3

1

phosphorylation

up-regulates activity

0.272

These results demonstrate that TRAF6 K63 ubiquitination might be regulated by an RSK2 mediated phosphorylation dependent mechanism and phosphorylation of TRAF6 at Ser46, 47 and 48 enhances its ubiquitin mediated inflammation signaling.

SIGNOR-278302

P31749

P12268

1

phosphorylation

up-regulates activity

0.386

Further, we have demonstrated an in vivo association of IMPDH and PKB/Akt by co‐immunoprecipitation from COS cells expressing a constitutively active form of PKB/Akt. Finally, we were able to show that this constitutively active PKB/Akt could phosphorylate IMPDH in vitro. Thus, the interplay between PKB/Akt and IMPDH reported here could suggest that PKB/Akt activation leads to IMPDH type II activation which in turn prepares the cell for entry into S phase.

SIGNOR-261262

P49336

P46531

1

phosphorylation

down-regulates

0.552

Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo.

SIGNOR-130640

P05107

Q05655

0

phosphorylation

up-regulates

0.329

In this study, we present evidence that pkc isoforms are the major protein kinases that phosphorylate the c terminus of the integrin cd18 chain in leukocytes. Ser-745 is identified as a novel phosphorylation site in the integrin cytoplasmic domain. Additionally, we show that a thr-758-phosphorylated integrin peptide can interact with 14-3-3 proteins in leukocyte lysates

SIGNOR-178897

Q92673

P02649

2

binding

up-regulates

0.62

Lr11 binds the apolipoprotein e (apoe)-rich lipoproteins, beta-very low density lipoproteins (vldls), with a high affinity similar to that of other members, such as the ldlr and vldl receptor.Incubation For 48 hours with beta-vldl of lr11-overexpressing cells, but not of control cells, promotes the appearance of numerous intracellular lipid droplets.

SIGNOR-110555

P63096

P30556

2

binding

up-regulates activity

0.25

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-256738

P29350

P12931

2

dephosphorylation

up-regulates activity

0.527

Several protein tyrosine phosphatases are capable of activating Src by dephosphorylating Y530 (reviewed in ref. 9). These include PTP-α, PTP-λ, SHP-1, SHP-2, and PTP1B

SIGNOR-248472

P05771

P04049

1

phosphorylation

up-regulates

0.445

Pkc can effectively phosphorylate raf-1, this is a direct effect of activated pkc and not the result of raf-1 autophosphorylation. the sites of pkc-mediated raf-1 phosphorylation are deduced to be ser497 and ser619.

SIGNOR-37474

P56211

Q96GX5

0

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

Q8TDC3

P23258

1

phosphorylation

up-regulates

0.248

Sadb kinases associate and phosphorylate gamma-tubulin on ser 131 s131d gamma-tubulin expression amplifies centrosome duplication

SIGNOR-187405

P30405

P49841

0

phosphorylation

up-regulates activity

0.378

Phosphorylation of cyclophilin D at serine 191 regulates mitochondrial permeability transition pore opening and cell death after ischemia-reperfusion|We conclude that CypD phosphorylation at S191 residue leads to its binding to OSCP and thus sensitizes mPTP opening for the subsequent cell death.|Under baseline condition (WT group), the phosphorylation of CypD by a kinase (e.g. GSK3beta) at S191 induces its translocation to the OSCP, to favor mPTP opening and subsequent cell death at reperfusion.

SIGNOR-264880

P01106

Q8N699

1

transcriptional regulation

up-regulates quantity by expression

0.298

MT-MC1 is a widely expressed nuclear protein whose overexpression, unlike that of c-Myc targets reported previously, recapitulates multiple c-Myc phenotypes. These include promotion of apoptosis, alteration of morphology, enhancement of anchorage-independent growth, tumorigenic conversion, promotion of genomic instability, and inhibition of hematopoietic differentiation. The MT-MC1 promoter is a direct c-Myc target; it contains two consensus E-box elements, both of which bind c-Myc.

SIGNOR-261736

Q06945

O00560

2

binding

up-regulates activity

0.538

Sox4 activation by IL-5R_ appears to be direct, with syntenin functioning as an adaptor molecule. Syntenin mediates IL-5induced Sox4 activation.

SIGNOR-223089

P63000

P15498

0

guanine nucleotide exchange factor

up-regulates activity

0.765

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-260581

Q16539

P03372

1

phosphorylation

up-regulates

0.625

Conversely, constitutively active mkk6 induced p38 mapk activation that recapitulated the effects of polyphenols by inducing eralpha phosphorylation and downstream activation of akt, and enos. The key role of eralpha ser-118 phosphorylation was confirmed in enos-transfected cos-7 cells

SIGNOR-136950

P35222

P55285

2

binding

up-regulates activity

0.578

At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin

SIGNOR-265868

P50148

Q99677

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-257383

P08238

Q8TF40

2

binding

down-regulates activity

0.2

FNIP1 and FNIP2 facilitate FLCN binding to Hsp90 chaperone. Our results suggest that FNIP1 is a potent inhibitor of Hsp90 ATPase activity, as 200 nM of FNIP1 inhibits Hsp90 ATPase activity by 50-fold. FNIP2 also has shown inhibitory activity towards Hsp90; however, it required 1.6 μM of FNIP2 to inhibit the ATPase activity by eightfold. Although we use the term ‘inhibition' here, FNIPs seem only to be slowing the chaperone cycle.

SIGNOR-261415

P38405

P32239

2

binding

up-regulates activity

0.265

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-256908

Q13131

Q6N021

1

phosphorylation

up-regulates quantity by stabilization

0.2

We identify the tumour suppressor TET2 as a substrate of the AMP-activated kinase (AMPK), which phosphorylates TET2 at serine 99, thereby stabilizing the tumour suppressor. Increased glucose levels impede AMPK-mediated phosphorylation at serine 99, which results in the destabilization of TET2 followed by dysregulation of both 5-hydroxymethylcytosine (5hmC) and the tumour suppressive function of TET2 in vitro and in vivo

SIGNOR-256134

A6ND36

P48729

2

binding

up-regulates quantity

0.373

We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.

SIGNOR-273745

P00738

Q9NZP8

0

cleavage

up-regulates activity

0.375

We demonstrate that coexpression of the proform of Hp (proHp) and C1r-LP in COS-1 cells effected cleavage of proHp in the endoplasmic reticulum. This cleavage depended on proteolytic activity of C1r-LP because mutation of the putative active-site Ser residue abolished the reaction. Furthermore, incubation of affinity-purified C1r-LP and proHp led to the cleavage of the latter protein. ProHp appeared to be cleaved at the expected site because substitution of Gly for Arg-161 blocked the reaction.

SIGNOR-256358

Q96LB2

P50148

2

binding

up-regulates activity

0.342

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-257384

P07195

O14965

0

phosphorylation

up-regulates activity

0.2

Aurora-A-mediated phosphorylation of LDHB serine 162 significantly increases its activity in reducing pyruvate to lactate, which efficiently promotes NAD+ regeneration, glycolytic flux, lactate production and bio-synthesis with glycolytic intermediates.

SIGNOR-277493

P24723

Q15139

1

phosphorylation

up-regulates

0.355

These results provide direct evidence that pkd becomes activated in vivo as a consequence of pkc-mediated phosphorylation of serines 744 and 748.

SIGNOR-66734

P08754

P48039

2

binding

up-regulates activity

0.498

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-256849

P12931

Q9Y2X7

1

phosphorylation

up-regulates activity

0.542

Tyrosines 246 and 293 are required to hold GIT1 in a closed conformation.Hyperphosphorylation of GIT1-N by Src and pervanadate does not affect its binding in vitro to full length GIT1 proteins. Mutations Y246E and Y293E of GIT1 enhance binding to paxillin.

SIGNOR-276627

P35568

Q15418

0

phosphorylation

down-regulates quantity by destabilization

0.358

Negative feedback involves s6k, which inactivates irs by phosphorylation at multiple sites, thus inducing its degradation and altered cell localization.

SIGNOR-175687

P12931

P52789

1

phosphorylation

up-regulates activity

0.362

Here we find that c-Src can interact with and phosphorylate hexokinases HK1 and HK2, the rate limiting enzymes in glycolysis.|Moreover, c-Src could efficiently stimulate the catalytic activities of HK1 and HK2, but failed to stimulate their corresponding mutants (XREF_FIG and XREF_SUPPLEMENTARY).

SIGNOR-278499

P23458

Q8NI17

2

binding

up-regulates

0.497

Il-31 can activate janus kinase (jak) 1 and jak2 signaling molecules after binding to its receptor complex.

SIGNOR-161342

Q2M2I8

Q96CW1

1

phosphorylation

up-regulates

0.79

Aak1 is enriched at presynaptic terminals, whereas in nonneuronal cells it colocalizes with clathrin and ap2 in clathrin-coated pits and at the leading edge of migrating cells. Aak1 specifically phosphorylates the mu subunit in vitro, and stage-specific assays for endocytosis show that mu phosphorylation by aak1 results in a decrease in ap2-stimulated transferrin internalization. Together, these results provide strong evidence that aak1 is the endogenous mu 2 kinase and plays a regulatory role in clathrin-mediated endocytosis.

SIGNOR-115657

Q9UNW8

P19086

2

binding

up-regulates activity

0.2

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-257275

P10451

P15036

0

transcriptional regulation

up-regulates quantity by expression

0.251

We demonstrated that Ets2 is capable of binding to and transactivating the OPN promoter using gel shift and transient transfection assays

SIGNOR-259872

P08754

P28223

2

binding

up-regulates activity

0.268

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-256885

O96013

Q16236

1

phosphorylation

down-regulates quantity by destabilization

0.2

PAK4 directly phosphorylated Nrf2 at T369, and it led to its nuclear export and proteasomal degradation, all of which impaired antioxidant responses in hepatocytes.

SIGNOR-277583

P05412

P17947

2

binding

up-regulates activity

0.555

These results indicate that AML1-ETO competes c-Jun away from binding to the β3β4 domain of PU.1. Thus, the c-Jun coactivation function of PU.1 is down-regulated and this in turn down-regulates transcriptional activity of PU.1.

SIGNOR-255660

P01042

P03952

0

cleavage

up-regulates activity

0.779

Bradykinin is a nonapeptide composed of the sequence Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg and functions as an inflammatory mediator. BK is the product of the kallikrein–kinin system following activation of FXII. FXIIa leads to proteolysis of PK, and the resulting PKa cleaves HK to generate BK (Figure 1).

SIGNOR-263548

P07101

P51812

0

phosphorylation

up-regulates

0.267

Mitogen-activated protein-kinase (map) kinase-activated protein kinases 1 and 2 (mapkap kinase-1, mapkap kinase-2), were found to phosphorylate bacterially expressed human tyrosine hydroxylaserecombinant human tyrosine hydroxylase (hth1) was found to be phosphorylated by mitogen and stress-activated protein kinase 1 (msk1) at ser40 and by p38 regulated/activated kinase (prak) on ser19. Phosphorylation by msk1 induced an increase in vmax

SIGNOR-34682

P43034

Q8WVJ2

2

binding

up-regulates quantity by stabilization

0.44

The type I lissencephaly gene product LIS1, a key regulator of cytoplasmic dynein, is critical for cell proliferation, survival, and neuronal migration. However, little is known about the regulation of LIS1. Here, we identify a previously uncharacterized mammalian homolog of Aspergillus NudC, NudCL2 (NudC-like protein 2), as a regulator of LIS1. NudCL2 is localized to the centrosome in interphase, and spindle poles and kinetochores during mitosis, a pattern similar to the localization of LIS1 and cytoplasmic dynein. Depletion of NudCL2 destabilized LIS1 and led to phenotypes resembling those of either dynein or LIS1 deficiency. NudCL2 complexed with and enhanced the interaction between LIS1 and Hsp90. Either disruption of the LIS1-Hsp90 interaction with the C terminus of NudCL2 or inhibition of Hsp90 chaperone function by geldanamycin decreased LIS1 stability.

SIGNOR-252167

P10721

Q06124

1

phosphorylation

up-regulates activity

0.684

SHP2 can be phosphorylated at 2 C-terminal tyrosyl residues by receptor tyrosine kinases, including KIT as well as cytosolic tyrosine kinases, including Src and Abl. The level of tyrosyl phosphorylation of SHP2 has been associated with its recruitment to the receptor.Thus, pharmacologic inhibition of SHP2 phosphatase function might permit SHP2 to return to its inactive conformation resulting in reduced tyrosine phosphorylation.

SIGNOR-256140

Q969H4

P54762

2

binding

up-regulates activity

0.293

The phosphorylated CNK1 interacts with ephrinB1. The binding of ephrinB1 to CNK1 connects RhoA and p115RhoGEF with ephrinB1-associated MKK4, promoting JNK activation and cell migration.

SIGNOR-275921

P05412

P01100

2

binding

up-regulates activity

0.953

The cFos proto-oncoprotein associates with cJun to form a heterodimer with increased DNA binding and transcriptional activities.

SIGNOR-252087

P08651

Q9HCE7

0

ubiquitination

down-regulates quantity

0.329

In addition, Smurf1 knockdown also blocked the degradation of endogenous NFI-C in response to TGF-beta1 (XREF_FIG).|In particular, Smurf1 and Smurf2 markedly increased the polyubiquitination of NFI-C in the presence of TGF-beta1 (XREF_FIG and XREF_SUPPLEMENTARY).

SIGNOR-278753