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
O14757	Q06609	1	phosphorylation	up-regulates	0.843	We demonstrate that chk1 interacts with rad51, and that rad51 is phosphorylated on thr 309 in a chk1-dependent manner	SIGNOR-133375
P05412	Q8TD08	0	phosphorylation	up-regulates	0.428	Up-regulation of c-jun mrna in cardiac myocytes requires the extracellular signal-regulated kinase cascade, but c-jun n-terminal kinases are required for efficient up-regulation of c-jun protein. these data suggest that erks, rather than jnks, are required for c- jun up-regulation.	SIGNOR-91375
Q16539	O43257	1	phosphorylation	up-regulates	0.314	We show that the srcap subunit named znhit1 or p18(hamlet), which is a substrate of p38 mapk, is recruited to the myogenin promoter at the onset of muscle differentiation, in a p38 mapk-dependent manner. Furthermore, p18hamlet was phosphorylated during myoblast differentiation in a p38 mapk-dependent manner (dal testo pmc)	SIGNOR-165571
Q16611	P10415	2	binding	down-regulates	0.677	Bcl-2 bind to bax or five other pro-apoptotic relatives (bak, bad, bik, bid or bim)	SIGNOR-55546
P63000	Q96P48	0	gtpase-activating protein	down-regulates activity	0.455	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-260451
P24394	P23458	2	binding	up-regulates	0.716	IL-4Rα, γc, and IL-13Rα1 all contain proline-rich box-1 regions that bind jak1, jak3, and tyk2, respectively. Il-4 uses the type ii receptor, and IL-13R1 Binds tyk2. Il-13 results in activation of jak1 and tyk2 in hematopoietic and nonhematopoietic cells.	SIGNOR-100774
P41240	P13639	1	phosphorylation	down-regulates quantity	0.264	C-terminal Src kinase (Csk)-mediated phosphorylation of eukaryotic elongation factor 2 (eEF2) promotes proteolytic cleavage and nuclear translocation of eEF2.\|In this report, we show that eukaryotic elongation factor 2 (eEF2) is a new protein substrate of Csk and could locate in the nucleus.	SIGNOR-279698
P08631	P19174	1	phosphorylation	up-regulates activity	0.681	The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors.	SIGNOR-249361
O14733	Q9NYL2	0	phosphorylation	up-regulates activity	0.2	We show here that members of the mixed-lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper kinase [DLK]) are expressed in neuronal cells and are likely to act between Rac1/Cdc42 and MKK4 and -7 in death signaling.	SIGNOR-243345
Q13489	Q9Y572	1	polyubiquitination	up-regulates activity	0.647	CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.	SIGNOR-272714
Q8WU20	P22681	0	ubiquitination	down-regulates	0.576	The experiments presented in this report illustrate that in response to fgf stimulation, cbl is recruited by grb2 binding to the frs2_ multiprotein complex, resulting in ubiquitination of frs2_ and fgfr. grb2 functions as a link between frs2_ and cbl;grb2 is bound to tyrosine-phosphorylated frs2_ by means of its sh2 domain and to a proline-rich region in the c terminus of cbl by means of its sh3 domains.	SIGNOR-87166
Q3KR16	P53350	0	phosphorylation	up-regulates	0.415	We reported previously that a guanine nucleotide exchange factor, myogef, localizes to the central spindle, activates rhoa, and is required for cytokinesis. In this study, we have found that plk1 (polo-like kinase 1) can phosphorylate myogef, thereby recruiting myogef to the central spindle as well as enhancing myogef activity toward rhoa. The in vitro kinase assay shows that plk1 can phosphorylate myogef on threonine 574.	SIGNOR-179954
P24941	P54198	1	phosphorylation	up-regulates activity	0.326	Hira bound to and was phosphorylated by cyclin a- and e-cdk2 in vitrohira became phosphorylated on threonine 555 in s phase when cyclin-cdk2 kinases are active.ectopic expression of hira in cells caused arrest in s phase and this is consistent with the notion that it is a cyclin-cdk2 substrate that has a role in control of the cell cycle.	SIGNOR-105548
Q9Y5H9	Q9Y5G4	2	binding	up-regulates activity	0.2	The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.	SIGNOR-265678
Q9Y5P4	P78368	0	phosphorylation	down-regulates	0.2	These results indicate that ckigamma2 hyperphosphorylates the serine-repeat motif of cert, thereby inactivating cert and down-regulating the synthesis of sphingomyelin.	SIGNOR-182160
P45983	P17275	1	phosphorylation	up-regulates activity	0.719	JunB-control of IL-4 expression is mediated by the phosphorylation of JunB at Thr102 and -104 by JNK MAP kinase. The synergy between c-Maf and JunB can be attributed to cooperative DNA binding, which is facilitated by JunB phosphorylation.	SIGNOR-250120
Q9UNH7	P08069	2	binding	down-regulates quantity	0.2	Here, we discovered that the binding between SNX-BARs and CI-MPR or IGF1R is mediated by the phox-homology (PX) domain of SNX5 or SNX6 and a bipartite motif, termed SNX-BAR-binding motif (SBM), in the cargoes. our studies establish that SNX-BARs function as a direct cargo-selecting module for a large set of transmembrane proteins transiting the endosome, in addition to their roles in phospholipid recognition and biogenesis of tubular structures.	SIGNOR-269445
Q6R327	P49840	0	phosphorylation	down-regulates quantity by destabilization	0.387	We show that this process is dependent on glycogen synthase kinase 3 (GSK3): GSK3 was associated with rictor and directly phosphorylated the Thr-1695 site in a putative CDC4 phospho-degron motif of rictor; mutation of this site impaired the interaction between rictor and FBXW7, decreased rictor ubiquitination, and increased rictor stability.	SIGNOR-276899
Q86TM6	P60604	0	ubiquitination	up-regulates activity	0.659	We show that human HRD1 is a non-glycosylated, stable ER protein with a cytosolic RING-H2 finger domain. In the presence of the ubiquitin-conjugating enzyme UBC7, the RING-H2 finger has in vitro ubiquitination activity for Lys(48)-specific polyubiquitin linkage, suggesting that human HRD1 is an E3 ubiquitin ligase involved in protein degradation.	SIGNOR-272593
P68400	P52655	1	phosphorylation	up-regulates activity	0.379	We now show that human TFIIA is phosphorylated in vivo on serine residues that are partially conserved between yeast and human TFIIA large subunits. Alanine substitution mutation of serine residues 316 and 321 in TFIIA alphabeta reduced TFIIA phosphorylation significantly in vivo. Additional alanine substitutions at serines 280 and 281 reduced phosphorylation to undetectable levels. Mutation of all four serine residues reduced the ability of TFIIA to stimulate transcription in transient transfection assays with various activators and promoters, indicating that TFIIA phosphorylation is required globally for optimal function.	SIGNOR-250877
Q13322	P27361	0	phosphorylation	up-regulates	0.298	Phosphorylation of grb10 by mitogen-activated protein kinase: identification of ser150 and ser476 of human grb10zeta as major phosphorylation sitesreplacing ser(150) and ser(476) with alanines reduced the inhibitory effect of human grb10zeta on insulin-stimulated irs1 tyrosine phosphorylation	SIGNOR-138171
Q12800	Q00526	0	phosphorylation	down-regulates	0.264	In vitro, lsf is phosphorylated by cyclin e/cyclin-dependent kinase 2 (cdk2), cyclin c/cdk2, and cyclin c/cdk3, predominantly on s309. Phosphorylation by cyclin c/cyclin-dependent kinase 2 following mitogenic stimulation of murine fibroblasts inhibits transcriptional activity of lsf during g1 progression	SIGNOR-184164
O94806	O96013	1	phosphorylation	up-regulates activity	0.252	PAK4 activity is regulated by an autoinhibitory domain that is released upon RhoGTPase binding as well as phosphorylation at Ser474 in the activation loop of the kinase domain. In the present study, we add another level of complexity to PAK4 regulation by showing that phosphorylation at Ser99 is required for its targeting to the leading edge. This phosphorylation is mediated by PKD1 (protein kinase D1)	SIGNOR-275931
P00533	P00533	2	phosphorylation	up-regulates activity	0.2	EGFR possesses three major and two minor tyrosine autophosphorylation sites located at Y1068, Y1148, Y1173, and at Y992 and Y1086 respectively. In addition, EGFR Y1114 is preceded by glutamic acid (Figure 1), which should be preferred by the EGFR kinase as indicated in previous work	SIGNOR-236527
Q14192	P10275	2	binding	up-regulates	0.522	Fhl2 contains a strong, autonomous transactivation function and binds specifically to the ar in vitro and in vivo.	SIGNOR-74703
P19419	Q99102	1	transcriptional regulation	up-regulates quantity by expression	0.2	Through promoter screening, overexpressing methods and luciferase reporter studies, we found that transcription factors CREB, Ets-1, Elk-1 and STAT1 can positively regulate MUC4 expression at the promoter and mRNA level.	SIGNOR-254096
Q13554	P49840	1	phosphorylation	down-regulates	0.291	Inhibitory phosphorylation of gsk-3 by camkii couples depolarization to neuronal survival.	SIGNOR-167962
P46531	O00548	2	binding	up-regulates activity	0.627	Notch signaling is a highly conserved pathway involved in cell fate choice during development with Delta and Jagged constituting the two evolutionary conserved families of Notch ligands. These ligands are transmembrane proteins with conserved biochemical structure that share their receptors and signal through a common mechanism. Upon ligand binding Notch receptors are proteoliticaly cleaved, the intracellular domain of Notch (NICD) is released and translocated to the nucleus, where it activates target genes. In mammals, four receptors and five ligands have been described. Delta-1, Delta-3 and Delta-4 are homologues to Drosophila Delta and Jagged-1 and Jagged-2 to Drosophila Serrate.	SIGNOR-209732
Q8N122	Q9UBE8	0	phosphorylation	down-regulates activity	0.327	NLK inhibits mTORC1 lysosomal localization and thereby suppresses mTORC1 activation. Mechanistically, NLK phosphorylates Raptor on S863 to disrupt its interaction with the Rag GTPase, which is important for mTORC1 lysosomal recruitment.	SIGNOR-273908
P10145	P25025	2	binding	up-regulates	0.86	Il-8 activates both the cxcr1 and the cxcr2 on microvascular endothelial cells, using different signal transduction cascades.	SIGNOR-107983
Q12851	Q9UQF2	2	binding	down-regulates	0.2	DLK mutants were used to demonstrate that a DLK leucine zipper-leucine zipper interaction is necessary for DLK dimerization and to show that DLK dimerization mediated by the leucine zipper domain is prerequisite for DLK activity and subsequent activation of stress-activated protein kinase (SAPK).	SIGNOR-75385
Q9UPW6	Q9C0K0	1	transcriptional regulation	down-regulates quantity	0.495	Satb2 represses the transcription of Nr4a2. The misexpression of Nr4a2 together with Ctip2 induces expression of SubC-specific genes in wild-type Rsp, and simultaneous knockdown of these two genes in Rsp Satb2-mutant cells prevents their fate transition to SubC identity. Thus, Satb2 serves as a determinant gene in the Rsp regionalization by repressing Nr4a2 and Ctip2 during cortical development	SIGNOR-268931
Q9NS23	O14965	0	phosphorylation	down-regulates	0.448	Aurora-a appears to phosphorylate rassf1a at threonine202 and/or serine203 that reside within the known microtubule-binding domain of rassf1a. Substitutions of these residues with glutamic acid at both positions, mimicking constitutive phosphorylation of rassf1a, disrupt rassf1a interactions with microtubules and abolish its ability to induce m-phase cell cycle arrest.	SIGNOR-155815
Q13547	Q99801	2	binding	down-regulates activity	0.369	NKX3.1 also binds HDAC1 and releases p53 from p53-MDM2-HDAC1 complex, promoting p53 acetylation and activity.	SIGNOR-251549
P12931	P42229	1	phosphorylation	up-regulates	0.75	Src can thus directly tyrosine-phosphorylate the activation site of stat5 (tyr 694 in stat5a), and src may contribute to epo-induced signal transduction via stat5.	SIGNOR-111078
Q9UQM7	O14490	1	phosphorylation	down-regulates quantity by destabilization	0.397	CaMKIIα activated by the NMDA receptor phosphorylates GKAP Ser54 to induce polyubiquitination of GKAP.	SIGNOR-276429
P06493	Q9UKX7	1	phosphorylation	down-regulates	0.421	These results suggest that both ERK and Cdk1 directly phosphorylate Nup50 at Ser221 in intact cells\|Notably, erk phosphorylation of the fg repeat region of nup50 reduced its affinity for importin-beta family proteins, importin-beta and transportin.	SIGNOR-188061
Q9NQS5	P63096	2	binding	up-regulates activity	0.284	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-256704
P06241	P08575	0	dephosphorylation	up-regulates activity	0.73	On the membrane SKAP55, via its phosphorylated Tyr-271, further binds the SH2 domain of Fyn to replace the low-affinity bound inhibitory site of the kinase. Consequently, CD45 may have transiently disassociated with the Tyr-232 residue of SKAP55 through dephosphorylation and simultaneously interacted with the released the phosphorylated inhibitory tyrosine residue of Fyn for dephosphorylation, resulting in activation of the Src family kinase Fyn and initiation of TCR-engaged signal transduction.	SIGNOR-248352
P28562	Q16539	2	dephosphorylation	down-regulates activity	0.805	The activity of MAPKs can be also regulated by a family of DUSPs (dual-specificity phosphatases)/MKPs (MAPK phosphatases), which dephosphorylate both phosphotyrosine and phosphothreonine residues MKPs 1, 4, 5 and 7 can dephosphorylate p38_ and p38_ in addition to JNK MAPKs. Importantly, some MKPs are transcriptionally up-regulated by stimuli that activate MAPK signalling, and are thought to play an important role limiting the extent of MAPK activation	SIGNOR-166571
P17612	P54296	1	phosphorylation	down-regulates	0.2	This binding is regulated in vitro by phosphorylation of a single serine residue (ser76) in the immediately adjacent amino-terminal domain mp1. M-protein phosphorylation by camp-dependent kinase a inhibits binding to myosin lmm.	SIGNOR-56395
P24941	P06401	1	phosphorylation	down-regulates	0.441	Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26s proteasome	SIGNOR-74708
P78352	Q9P1A6	2	binding	up-regulates activity	0.705	SAPAPs are specifically expressed in neuronal cells and enriched in the PSD fraction. SAPAPs induce the enrichment of PSD-95/SAP90 to the plasma membrane in transfected cells. Thus, SAPAPs may have a potential activity to maintain the structure of PSD by concentrating its components to the membrane area.	SIGNOR-264210
P11274	Q8TBB1	0	ubiquitination	down-regulates quantity by destabilization	0.267	We used the Ligand of Numb protein X (LNX) family of E3s, a group of PDZ domain-containing RING-type E3 ubiquitin ligases, to demonstrate the feasibility of this strategy. Many potential substrates of LNX E3s were identified. Eight of the nine selected candidates were ubiquitinated in vitro, and two novel endogenous substrates, PDZ-binding kinase (PBK) and breakpoint cluster region protein (BCR), were confirmed in vivo.	SIGNOR-272903
Q14814	Q9UKX2	1	transcriptional regulation	up-regulates quantity by expression	0.327	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238712
P63092	Q01726	2	binding	up-regulates activity	0.481	The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins	SIGNOR-268697
Q9Y6D9	O43683	0	relocalization	up-regulates activity	0.727	Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity	SIGNOR-252017
P18846	P18146	1	transcriptional regulation	up-regulates quantity by expression	0.275	Phosphorylated CREB and ATF1 then bind to the CRE of the egr-1 promoter and cause a stress-dependent transcriptional activation of this gene.	SIGNOR-271686
P36956	P27361	0	phosphorylation	up-regulates activity	0.443	Map kinases erk1/2 phosphorylate sterol regulatory element-binding protein (srebp)-1a at serine 117 in vitro. mutation of serine 117 to alanine abolished erk2-mediated phosphorylation in vitro and the map kinase-related transcriptional activation of srebp-1a by insulin and platelet-derived growth factor in vivo.	SIGNOR-80096
Q05513	Q9GZQ8	1	phosphorylation	down-regulates activity	0.2	LC3B is phosphorylated at Thr-50 within the LDS by serine/threonine kinase (STK) 3 and STK4. Here, we identified LIR motifs in STK3 and atypical protein kinase Cζ (PKCζ) and never in mitosis A (NIMA)-related kinase 9 (NEK9). All three kinases phosphorylated LC3B Thr-50 in vitro A phospho-mimicking substitution of Thr-50 impaired binding of several LIR-containing proteins, such as ATG4B, FYVE, and coiled-coil domain-containing 1 (FYCO1), and autophagy cargo receptors p62/sequestosome 1 (SQSTM1) and neighbor of BRCA1 gene (NBR1).	SIGNOR-273906
P04637	P48730	0	phosphorylation	up-regulates	0.578	Here we show that the direct association between a p53 n-terminal peptide and mdm2 is disrupted by phosphorylation of the peptide on thr(18) but not by phosphorylation at other n-terminal sites, including ser(15) and ser(37). Thr(18) was phosphorylated in vitro by casein kinase (ck1).	SIGNOR-75889
Q5T3J3	Q96T88	0	ubiquitination	down-regulates activity	0.2	In our study, we found the UHRF1 is sufficient to suppress RIF1 accumulation at DSBs in S phase and CtIP functions as a negative regulator of RIF1 only in G2 phase (XREF_FIG; XREF_SUPPLEMENTARY).\|UHRF1 ubiquitinates RIF1.	SIGNOR-278604
Q9Y5X2	O14920	2	binding	up-regulates activity	0.2	IFNγ induced JAK1-mediated phosphorylation of SNX8 at Tyr95 and Tyr126, which promoted the recruitment of IKKβ to the JAK1 complex.	SIGNOR-273646
Q9NYJ8	Q13546	2	binding	up-regulates activity	0.864	TNF_ induced the polyubiquitination of RIP and the association of polyubiquitinated RIP with TAB2.	SIGNOR-128406
P17542	P25800	2	binding	up-regulates	0.736	Transcriptional activity of tal1 in t cell acute lymphoblastic leukemia (t-all) requires rbtn1 or -2	SIGNOR-46114
O95644	Q13627	0	phosphorylation	up-regulates activity	0.429	DYRK1A phosphorylation of NFATc1 and alphaA at S261, S278, S403 and S409 interfered with NFATc1 ubiquitination and ubiquitin-proteasome degradation.\|Here, we demonstrated that DYRK1A increased NFATc1 (NFATc1 and alphaA isoform) protein stability, in contrast to the decrease of NFATc2 protein stability by DYRK1A.	SIGNOR-278278
Q99835	P08754	2	binding	up-regulates	0.429	Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling.	SIGNOR-199165
Q13153	P17600	1	phosphorylation	up-regulates activity	0.349	Synapsin I is phosphorylated at Ser603 by p21-activated kinases. the Ser603 residue must be one of the pivotal sites for the release	SIGNOR-250235
P01116	Q8N431	2	binding	up-regulates	0.2	Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.	SIGNOR-161508
O95837	P41146	2	binding	up-regulates activity	0.353	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-257209
P22415	P78347	2	binding	up-regulates activity	0.489	TFII-I has been shown to interact with USF and to associate with either E-box elements or initiator sequences to activate gene transcription	SIGNOR-268538
P51955	Q8N137	1	phosphorylation	down-regulates activity	0.35	The opposite outcomes in NEK2- and centrobin-depleted cells suggest that NEK2 antagonizes biological functions of centrobin.\|These results suggest that NEK2 phosphorylates specific sites of centrobin, which are distinct from the PLK1 phosphorylation sites.	SIGNOR-279545
P17861	P60900	2	binding	down-regulates quantity by destabilization	0.303	We saw preferential binding of XBP-1u to subunits _5, _6 and _7.2. We demonstrate that XBP-1u undergoes efficient degradation in vitro by 20S proteasomes in the absence of ubiquitination.	SIGNOR-239039
P25445	Q99683	2	binding	up-regulates	0.694	Ask1 binds fas	SIGNOR-109676
P78509	O15409	0	transcriptional regulation	up-regulates quantity by expression	0.365	By interacting with CASK, TBR1 regulates several ASD candidate genes, such as GRIN2B, AUTS2 and RELN—all of which are recurrently mutated in ASD. In areas of the brain with overlapping expression patterns, such as in glutamatergic layer 6 neurons, the TBR1–FOXP2 interaction may result in co-ordinated regulation of common downstream targets.	SIGNOR-266833
P29474	P07900	2	binding	up-regulates	0.76	The binding of hsp90 to enos enhances the activation of enos.	SIGNOR-57211
P04637	Q70YC5	1	transcriptional regulation	up-regulates quantity by expression	0.29	Here, analysis of p53-regulated genes activated in the setting of telomere dysfunction identified Zfp365 (ZNF365 in humans) as a direct p53 target that promotes genome stability\| Our study identified ZNF365 as a necessary target whose activation by p53 in the presence of critically short telomeres contributes to genomic stability. We provide evidence that loss of ZNF365 leads to increased expression of CFS and dysfunctional telomeres, aberrant sister telomere recombination, and increased aneuploidy	SIGNOR-272476
Q8N5U6	P50222	2	binding	up-regulates activity	0.375	RFN10 co-immunoprecipitates with MEOX2. RNF10 potentiates MEOX2 transcriptional activation	SIGNOR-236968
Q9UK99	Q13501	2	binding	down-regulates quantity by destabilization	0.2	F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation. Here we show that another F-box protein Fbxo3, belonging to the FBXO type protein family, also interacts with and targets Smurf1 for poly-ubiquitination and proteasomal degradation. The SCF complex is composed of F-box protein, Skp1, Cullin1 (Cul1) and ROC1. Fbxo3, whose substrates are few, forms SCF Fbxo3 ubiquitin ligase and regulates the degradations of Fbxl2, p62, HIPK2 and p300 through the ubiquitin-proteasome pathway.	SIGNOR-272444
Q15208	O14980	1	phosphorylation	up-regulates activity	0.2	We further uncover that STK38 modulates XPO1 export activity by phosphorylating XPO1 on serine 1055, thus regulating its own nuclear exit.	SIGNOR-277483
Q01105	P48736	0	phosphorylation	up-regulates activity	0.336	We show that PI3Kgamma phosphorylates I2PP2A on serine 9 and 93 residues resulting in enhanced interaction of I2PP2A with PP2A.	SIGNOR-278320
P31749	O95988	2	binding	up-regulates	0.671	In vivo, tcl1 forms trimers, which associate with akt. Tcl1 facilitates the oligomerization and activation of akt. Our data show that tcl1 is a novel akt kinase coactivator, which promotes akt-induced cell survival and proliferation.	SIGNOR-81713
Q8IZP0	P06493	0	phosphorylation	down-regulates activity	0.419	We identified serine 216 of Abi1 as a target of CDK1/cyclin B kinase that is phosphorylated in cells at the onset of mitosis.\|Bcr-Abl-induced actin polymerization requires the Abi1 pathway, as the blockade of the signal transduction from Bcr-Abl to Abi1 abolishes the F-actin assembly\|serine phosphorylation of Abi1 by CDK1/cyclin B serves as a cell cycle-dependent regulatory mechanism that inhibits actin assembly	SIGNOR-264421
P16949	P45984	0	phosphorylation	down-regulates	0.256	Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. Here we show that in response to hyperosmotic stress, jnk phosphorylates a key cytoplasmic microtubule regulatory protein, stathmin (stmn), on conserved ser-25 and ser-38 residues. In in vitro biochemical studies, we identified stmn ser-38 as the critical residue required for efficient phosphorylation by jnk and identified a novel kinase interaction domain in stmn required for recognition by jnk. We revealed that jnk was required for microtubule stabilization in response to hyperosmotic stress.	SIGNOR-166698
P17612	O95295	1	phosphorylation	up-regulates activity	0.307	PKA-phosphorylation of Snapin significantly increases its binding to synaptosomal-associated protein-25 (SNAP-25). Mutation of Snapin serine 50 to aspartic acid (S50D) mimics this effect of PKA phosphorylation	SIGNOR-250053
Q05209	Q9Y6E0	0	phosphorylation	down-regulates activity	0.272	In addition, MST3 can phosphorylate PTP-PEST and inhibit the tyrosine phosphatase activity of PTP-PEST.\|MST3 directly phosphorylates and inactivates protein tyrosine phosphatase PTP-PEST, which enhances cell migration by enhancing the tyrosine phosphorylation of paxillin Y31 and Y118 [ ].	SIGNOR-279127
P23769	P10827	2	binding	down-regulates activity	0.2	We found that the T3-bound TR inhibits this reporter construct driven by GATA2 alone, indicating that the target of T3-bound TR repression is GATA2.	SIGNOR-267257
Q92831	Q00987	0	ubiquitination	down-regulates quantity by destabilization	0.621	Consistently, overexpression of MDM2 in p53 null cells caused the reduction of the protein level of PCAF, but not the mRNA level.\|MDM2 ubiquitinated PCAF in vitro and in cells.	SIGNOR-278825
Q9HC97	P63096	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-256717
Q9NRY6	Q05655	0	phosphorylation	up-regulates	0.457	Ad198-activated pkc-delta induces phosphorylation of mitochondrial pls3 at thr21;pls3 is a critical downstream effector of pkc-delta in ad198-induced apoptosis.	SIGNOR-140759
P28358	P09429	2	binding	up-regulates activity	0.292	We show that HMG1 interacts with proteins encoded by the HOX gene family by establishing protein-protein contacts between the HMG box domains and the HOX homeodomain. HMG1 enhances, in a dose-dependent fashion, the sequence-specific DNA binding activity in vitro, and the transcriptional activation in a co-transfection assay in vivo, of the HOXD9 protein.	SIGNOR-240556
Q96J02	Q7Z434	1	ubiquitination	down-regulates quantity by destabilization	0.646	These data collectively indicate that AIP4 is the E3 ligase for MAVS.\|We generated single substitutions (K362A, K371A or K420A) and combined point substitutions of MAVS and tested their degradation. K371A or K420A MAVS showed partial resistance to PCBP2-induced degradation (data not shown), whereas MAVS with the combined substitutions K371A and K420A (KK-AA) completely withstood the degradation	SIGNOR-260362
P43405	Q8N884	1	phosphorylation	up-regulates activity	0.2	Mechanistically, viral infection or foreign DNA transfection triggers recruitment of the spleen tyrosine kinase (SYK) and cGAS to the endosomal vacuolar H+ pump (V-ATPase), where SYK is activated and then phosphorylates human cGASY214/215 (mouse cGasY200/201) to prime its activation.	SIGNOR-277844
Q9UQB3	P22223	2	binding	up-regulates quantity by stabilization	0.294	To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member.	SIGNOR-252130
P32238	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-257236
Q02156	Q9H9S0	1	phosphorylation	up-regulates activity	0.329	Taken together, our results demonstrate that PKC\u03b5-mediated phosphorylation at T200 and T280 enhances Nanog protein stability in head and neck squamous cell carcinoma.\|These observations confirm that PKCepsilon modulates Nanog transcriptional activity and demonstrate that Nanog is phosphorylated by PKCepsilon at T200 and T280 in vivo.	SIGNOR-278203
Q14938	P54756	1	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268909
Q6UWZ7	Q13315	0	phosphorylation	up-regulates activity	0.2	In this study, we demonstrate that ionizing radiation (IR)-induces ATM-dependent phosphorylation of serine 404 (S404) next to the pSPxF motif. Crystal structures of BRCT/Abraxas show that phosphorylation of S404 is important for extensive interactions through the N-terminal sequence outside the pSPxF motif and leads to formation of a stable dimer.	SIGNOR-255587
Q14344	Q9Y2T6	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-256670
Q01726	P43250	0	phosphorylation	down-regulates activity	0.313	Overexpression of GRK6 Inhibits Agonist-Induced cAMP Production in HBL Human Melanoma Cells, without Affecting MC1R Gene Expression	SIGNOR-252389
Q9UKB1	Q9Y2X9	1	ubiquitination	down-regulates quantity by destabilization	0.2	E3 ligase the beta-transducin repeat-containing protein 2 (beta-TrCP2) governs the ubiquitination and degradation of ZNF281. In human CRC specimens, endogenous beta-TrCP2 were inversely correlated with ZNF281.	SIGNOR-264897
P49768	Q9NZ42	0	cleavage	up-regulates	0.959	Our data reveal a direct role of pen-2 in proteolytic cleavage of ps1 and a regulatory function of aph-1, in coordination with pen-2, in the biogenesis of the ps1 complex.	SIGNOR-97113
Q86UR1	A1X283	2	binding	up-regulates activity	0.347	Tks4 and Tks5 bind NoxA1 through their SH3 domains in a Rac-independent manner\|NoxO1 is required for full Nox1 and Nox3 oxidase activity at least partially because of its role in the plasma membrane recruitment of the NoxA1 activator protein\|Tks4 and Tks5 support Nox1- and Nox3-dependent ROS generation	SIGNOR-264707
P17612	P13807	1	phosphorylation	down-regulates activity	0.508	The results presented in this paper show that the phosphorylation of glycogen synthetase a by cyclic AMP-dependent protein kinase results in the phosphorylation of two distinct serines termed site-l and site-2, which account for 90% of the total phosphorylation	SIGNOR-253009
Q16665	Q9Y3V2	0	sumoylation	up-regulates	0.457	Rsume,_a small_rwd-containing protein, enhances sumo conjugation and stabilizes hif-1alpha during hypoxia	SIGNOR-158590
Q04912	P26927	2	binding	up-regulates	0.896	P185ron is a tyrosine kinase activated by msp	SIGNOR-31107
P24666	P29317	1	dephosphorylation	down-regulates activity	0.66	The SAM domain tyrosine Y960 which has been implicated in downstream PI3K signaling is dephosphorylated exclusively by HCPTP-B. The activation loop tyrosine (Y772) which directly controls kinase activity is dephosphorylated about six times faster by HCPTP-A. In contrast, the juxtamembrane tyrosines (Y575, Y588 and Y594) which are implicated in both control of kinase activity and downstream signaling are dephosphorylated by both variants with similar rates	SIGNOR-246023
P45984	P49768	1	phosphorylation	up-regulates	0.376	This jnk phosphorylation of ps1 at ser(319)thr(320) enhances the stability of the ps1 c-terminal fragment that is necessary for gamma-secretase activity.	SIGNOR-179676
Q00535	P35712	1	phosphorylation	down-regulates quantity	0.366	GST-Sox6 was phosphorylated in vitro by Cdk5 and p35 (XREF_FIG).\|Inhibition of Cdk5 activity by DN Cdk5 and roscovitine increases the Sox6 expression in primary cortical neurons.	SIGNOR-279365
P30304	Q15208	0	phosphorylation	down-regulates quantity	0.247	Here, we demonstrate that the depletion of serine-threonine kinase 38 (STK38) prevents the DNA-damage-induced degradation of CDC25A and subsequent G2 arrest, and that STK38 directly phosphorylates CDC25A at Ser-76, resulting in CDC25A's degradation.	SIGNOR-279488

O14757

Q06609

1

phosphorylation

up-regulates

0.843

We demonstrate that chk1 interacts with rad51, and that rad51 is phosphorylated on thr 309 in a chk1-dependent manner

SIGNOR-133375

P05412

Q8TD08

0

phosphorylation

up-regulates

0.428

Up-regulation of c-jun mrna in cardiac myocytes requires the extracellular signal-regulated kinase cascade, but c-jun n-terminal kinases are required for efficient up-regulation of c-jun protein. these data suggest that erks, rather than jnks, are required for c- jun up-regulation.

SIGNOR-91375

Q16539

O43257

1

phosphorylation

up-regulates

0.314

We show that the srcap subunit named znhit1 or p18(hamlet), which is a substrate of p38 mapk, is recruited to the myogenin promoter at the onset of muscle differentiation, in a p38 mapk-dependent manner. Furthermore, p18hamlet was phosphorylated during myoblast differentiation in a p38 mapk-dependent manner (dal testo pmc)

SIGNOR-165571

Q16611

P10415

2

binding

down-regulates

0.677

Bcl-2 bind to bax or five other pro-apoptotic relatives (bak, bad, bik, bid or bim)

SIGNOR-55546

P63000

Q96P48

0

gtpase-activating protein

down-regulates activity

0.455

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-260451

P24394

P23458

2

binding

up-regulates

0.716

IL-4Rα, γc, and IL-13Rα1 all contain proline-rich box-1 regions that bind jak1, jak3, and tyk2, respectively. Il-4 uses the type ii receptor, and IL-13R1 Binds tyk2. Il-13 results in activation of jak1 and tyk2 in hematopoietic and nonhematopoietic cells.

SIGNOR-100774

P41240

P13639

1

phosphorylation

down-regulates quantity

0.264

C-terminal Src kinase (Csk)-mediated phosphorylation of eukaryotic elongation factor 2 (eEF2) promotes proteolytic cleavage and nuclear translocation of eEF2.|In this report, we show that eukaryotic elongation factor 2 (eEF2) is a new protein substrate of Csk and could locate in the nucleus.

SIGNOR-279698

P08631

P19174

1

phosphorylation

up-regulates activity

0.681

The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors.

SIGNOR-249361

O14733

Q9NYL2

0

phosphorylation

up-regulates activity

0.2

We show here that members of the mixed-lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper kinase [DLK]) are expressed in neuronal cells and are likely to act between Rac1/Cdc42 and MKK4 and -7 in death signaling.

SIGNOR-243345

Q13489

Q9Y572

1

polyubiquitination

up-regulates activity

0.647

CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.

SIGNOR-272714

Q8WU20

P22681

0

ubiquitination

down-regulates

0.576

The experiments presented in this report illustrate that in response to fgf stimulation, cbl is recruited by grb2 binding to the frs2_ multiprotein complex, resulting in ubiquitination of frs2_ and fgfr. grb2 functions as a link between frs2_ and cbl;grb2 is bound to tyrosine-phosphorylated frs2_ by means of its sh2 domain and to a proline-rich region in the c terminus of cbl by means of its sh3 domains.

SIGNOR-87166

Q3KR16

P53350

0

phosphorylation

up-regulates

0.415

We reported previously that a guanine nucleotide exchange factor, myogef, localizes to the central spindle, activates rhoa, and is required for cytokinesis. In this study, we have found that plk1 (polo-like kinase 1) can phosphorylate myogef, thereby recruiting myogef to the central spindle as well as enhancing myogef activity toward rhoa. The in vitro kinase assay shows that plk1 can phosphorylate myogef on threonine 574.

SIGNOR-179954

P24941

P54198

1

phosphorylation

up-regulates activity

0.326

Hira bound to and was phosphorylated by cyclin a- and e-cdk2 in vitrohira became phosphorylated on threonine 555 in s phase when cyclin-cdk2 kinases are active.ectopic expression of hira in cells caused arrest in s phase and this is consistent with the notion that it is a cyclin-cdk2 substrate that has a role in control of the cell cycle.

SIGNOR-105548

Q9Y5H9

Q9Y5G4

2

binding

up-regulates activity

0.2

The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.

SIGNOR-265678

Q9Y5P4

P78368

0

phosphorylation

down-regulates

0.2

These results indicate that ckigamma2 hyperphosphorylates the serine-repeat motif of cert, thereby inactivating cert and down-regulating the synthesis of sphingomyelin.

SIGNOR-182160

P45983

P17275

1

phosphorylation

up-regulates activity

0.719

JunB-control of IL-4 expression is mediated by the phosphorylation of JunB at Thr102 and -104 by JNK MAP kinase. The synergy between c-Maf and JunB can be attributed to cooperative DNA binding, which is facilitated by JunB phosphorylation.

SIGNOR-250120

Q9UNH7

P08069

2

binding

down-regulates quantity

0.2

Here, we discovered that the binding between SNX-BARs and CI-MPR or IGF1R is mediated by the phox-homology (PX) domain of SNX5 or SNX6 and a bipartite motif, termed SNX-BAR-binding motif (SBM), in the cargoes. our studies establish that SNX-BARs function as a direct cargo-selecting module for a large set of transmembrane proteins transiting the endosome, in addition to their roles in phospholipid recognition and biogenesis of tubular structures.

SIGNOR-269445

Q6R327

P49840

0

phosphorylation

down-regulates quantity by destabilization

0.387

We show that this process is dependent on glycogen synthase kinase 3 (GSK3): GSK3 was associated with rictor and directly phosphorylated the Thr-1695 site in a putative CDC4 phospho-degron motif of rictor; mutation of this site impaired the interaction between rictor and FBXW7, decreased rictor ubiquitination, and increased rictor stability.

SIGNOR-276899

Q86TM6

P60604

0

ubiquitination

up-regulates activity

0.659

We show that human HRD1 is a non-glycosylated, stable ER protein with a cytosolic RING-H2 finger domain. In the presence of the ubiquitin-conjugating enzyme UBC7, the RING-H2 finger has in vitro ubiquitination activity for Lys(48)-specific polyubiquitin linkage, suggesting that human HRD1 is an E3 ubiquitin ligase involved in protein degradation.

SIGNOR-272593

P68400

P52655

1

phosphorylation

up-regulates activity

0.379

We now show that human TFIIA is phosphorylated in vivo on serine residues that are partially conserved between yeast and human TFIIA large subunits. Alanine substitution mutation of serine residues 316 and 321 in TFIIA alphabeta reduced TFIIA phosphorylation significantly in vivo. Additional alanine substitutions at serines 280 and 281 reduced phosphorylation to undetectable levels. Mutation of all four serine residues reduced the ability of TFIIA to stimulate transcription in transient transfection assays with various activators and promoters, indicating that TFIIA phosphorylation is required globally for optimal function.

SIGNOR-250877

Q13322

P27361

0

phosphorylation

up-regulates

0.298

Phosphorylation of grb10 by mitogen-activated protein kinase: identification of ser150 and ser476 of human grb10zeta as major phosphorylation sitesreplacing ser(150) and ser(476) with alanines reduced the inhibitory effect of human grb10zeta on insulin-stimulated irs1 tyrosine phosphorylation

SIGNOR-138171

Q12800

Q00526

0

phosphorylation

down-regulates

0.264

In vitro, lsf is phosphorylated by cyclin e/cyclin-dependent kinase 2 (cdk2), cyclin c/cdk2, and cyclin c/cdk3, predominantly on s309. Phosphorylation by cyclin c/cyclin-dependent kinase 2 following mitogenic stimulation of murine fibroblasts inhibits transcriptional activity of lsf during g1 progression

SIGNOR-184164

O94806

O96013

1

phosphorylation

up-regulates activity

0.252

PAK4 activity is regulated by an autoinhibitory domain that is released upon RhoGTPase binding as well as phosphorylation at Ser474 in the activation loop of the kinase domain. In the present study, we add another level of complexity to PAK4 regulation by showing that phosphorylation at Ser99 is required for its targeting to the leading edge. This phosphorylation is mediated by PKD1 (protein kinase D1)

SIGNOR-275931

P00533

2

phosphorylation

up-regulates activity

0.2

EGFR possesses three major and two minor tyrosine autophosphorylation sites located at Y1068, Y1148, Y1173, and at Y992 and Y1086 respectively. In addition, EGFR Y1114 is preceded by glutamic acid (Figure 1), which should be preferred by the EGFR kinase as indicated in previous work

SIGNOR-236527

Q14192

P10275

2

binding

up-regulates

0.522

Fhl2 contains a strong, autonomous transactivation function and binds specifically to the ar in vitro and in vivo.

SIGNOR-74703

P19419

Q99102

1

transcriptional regulation

up-regulates quantity by expression

0.2

Through promoter screening, overexpressing methods and luciferase reporter studies, we found that transcription factors CREB, Ets-1, Elk-1 and STAT1 can positively regulate MUC4 expression at the promoter and mRNA level.

SIGNOR-254096

Q13554

P49840

1

phosphorylation

down-regulates

0.291

Inhibitory phosphorylation of gsk-3 by camkii couples depolarization to neuronal survival.

SIGNOR-167962

P46531

O00548

2

binding

up-regulates activity

0.627

Notch signaling is a highly conserved pathway involved in cell fate choice during development with Delta and Jagged constituting the two evolutionary conserved families of Notch ligands. These ligands are transmembrane proteins with conserved biochemical structure that share their receptors and signal through a common mechanism. Upon ligand binding Notch receptors are proteoliticaly cleaved, the intracellular domain of Notch (NICD) is released and translocated to the nucleus, where it activates target genes. In mammals, four receptors and five ligands have been described. Delta-1, Delta-3 and Delta-4 are homologues to Drosophila Delta and Jagged-1 and Jagged-2 to Drosophila Serrate.

SIGNOR-209732

Q8N122

Q9UBE8

0

phosphorylation

down-regulates activity

0.327

NLK inhibits mTORC1 lysosomal localization and thereby suppresses mTORC1 activation. Mechanistically, NLK phosphorylates Raptor on S863 to disrupt its interaction with the Rag GTPase, which is important for mTORC1 lysosomal recruitment.

SIGNOR-273908

P10145

P25025

2

binding

up-regulates

0.86

Il-8 activates both the cxcr1 and the cxcr2 on microvascular endothelial cells, using different signal transduction cascades.

SIGNOR-107983

Q12851

Q9UQF2

2

binding

down-regulates

0.2

DLK mutants were used to demonstrate that a DLK leucine zipper-leucine zipper interaction is necessary for DLK dimerization and to show that DLK dimerization mediated by the leucine zipper domain is prerequisite for DLK activity and subsequent activation of stress-activated protein kinase (SAPK).

SIGNOR-75385

Q9UPW6

Q9C0K0

1

transcriptional regulation

down-regulates quantity

0.495

Satb2 represses the transcription of Nr4a2. The misexpression of Nr4a2 together with Ctip2 induces expression of SubC-specific genes in wild-type Rsp, and simultaneous knockdown of these two genes in Rsp Satb2-mutant cells prevents their fate transition to SubC identity. Thus, Satb2 serves as a determinant gene in the Rsp regionalization by repressing Nr4a2 and Ctip2 during cortical development

SIGNOR-268931

Q9NS23

O14965

0

phosphorylation

down-regulates

0.448

Aurora-a appears to phosphorylate rassf1a at threonine202 and/or serine203 that reside within the known microtubule-binding domain of rassf1a. Substitutions of these residues with glutamic acid at both positions, mimicking constitutive phosphorylation of rassf1a, disrupt rassf1a interactions with microtubules and abolish its ability to induce m-phase cell cycle arrest.

SIGNOR-155815

Q13547

Q99801

2

binding

down-regulates activity

0.369

NKX3.1 also binds HDAC1 and releases p53 from p53-MDM2-HDAC1 complex, promoting p53 acetylation and activity.

SIGNOR-251549

P12931

P42229

1

phosphorylation

up-regulates

0.75

Src can thus directly tyrosine-phosphorylate the activation site of stat5 (tyr 694 in stat5a), and src may contribute to epo-induced signal transduction via stat5.

SIGNOR-111078

Q9UQM7

O14490

1

phosphorylation

down-regulates quantity by destabilization

0.397

CaMKIIα activated by the NMDA receptor phosphorylates GKAP Ser54 to induce polyubiquitination of GKAP.

SIGNOR-276429

P06493

Q9UKX7

1

phosphorylation

down-regulates

0.421

These results suggest that both ERK and Cdk1 directly phosphorylate Nup50 at Ser221 in intact cells|Notably, erk phosphorylation of the fg repeat region of nup50 reduced its affinity for importin-beta family proteins, importin-beta and transportin.

SIGNOR-188061

Q9NQS5

P63096

2

binding

up-regulates activity

0.284

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-256704

P06241

P08575

0

dephosphorylation

up-regulates activity

0.73

On the membrane SKAP55, via its phosphorylated Tyr-271, further binds the SH2 domain of Fyn to replace the low-affinity bound inhibitory site of the kinase. Consequently, CD45 may have transiently disassociated with the Tyr-232 residue of SKAP55 through dephosphorylation and simultaneously interacted with the released the phosphorylated inhibitory tyrosine residue of Fyn for dephosphorylation, resulting in activation of the Src family kinase Fyn and initiation of TCR-engaged signal transduction.

SIGNOR-248352

P28562

Q16539

2

dephosphorylation

down-regulates activity

0.805

The activity of MAPKs can be also regulated by a family of DUSPs (dual-specificity phosphatases)/MKPs (MAPK phosphatases), which dephosphorylate both phosphotyrosine and phosphothreonine residues MKPs 1, 4, 5 and 7 can dephosphorylate p38_ and p38_ in addition to JNK MAPKs. Importantly, some MKPs are transcriptionally up-regulated by stimuli that activate MAPK signalling, and are thought to play an important role limiting the extent of MAPK activation

SIGNOR-166571

P17612

P54296

1

phosphorylation

down-regulates

0.2

This binding is regulated in vitro by phosphorylation of a single serine residue (ser76) in the immediately adjacent amino-terminal domain mp1. M-protein phosphorylation by camp-dependent kinase a inhibits binding to myosin lmm.

SIGNOR-56395

P24941

P06401

1

phosphorylation

down-regulates

0.441

Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26s proteasome

SIGNOR-74708

P78352

Q9P1A6

2

binding

up-regulates activity

0.705

SAPAPs are specifically expressed in neuronal cells and enriched in the PSD fraction. SAPAPs induce the enrichment of PSD-95/SAP90 to the plasma membrane in transfected cells. Thus, SAPAPs may have a potential activity to maintain the structure of PSD by concentrating its components to the membrane area.

SIGNOR-264210

P11274

Q8TBB1

0

ubiquitination

down-regulates quantity by destabilization

0.267

We used the Ligand of Numb protein X (LNX) family of E3s, a group of PDZ domain-containing RING-type E3 ubiquitin ligases, to demonstrate the feasibility of this strategy. Many potential substrates of LNX E3s were identified. Eight of the nine selected candidates were ubiquitinated in vitro, and two novel endogenous substrates, PDZ-binding kinase (PBK) and breakpoint cluster region protein (BCR), were confirmed in vivo.

SIGNOR-272903

Q14814

Q9UKX2

1

transcriptional regulation

up-regulates quantity by expression

0.327

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

SIGNOR-238712

P63092

Q01726

2

binding

up-regulates activity

0.481

The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins

SIGNOR-268697

Q9Y6D9

O43683

0

relocalization

up-regulates activity

0.727

Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity

SIGNOR-252017

P18846

P18146

1

transcriptional regulation

up-regulates quantity by expression

0.275

Phosphorylated CREB and ATF1 then bind to the CRE of the egr-1 promoter and cause a stress-dependent transcriptional activation of this gene.

SIGNOR-271686

P36956

P27361

0

phosphorylation

up-regulates activity

0.443

Map kinases erk1/2 phosphorylate sterol regulatory element-binding protein (srebp)-1a at serine 117 in vitro. mutation of serine 117 to alanine abolished erk2-mediated phosphorylation in vitro and the map kinase-related transcriptional activation of srebp-1a by insulin and platelet-derived growth factor in vivo.

SIGNOR-80096

Q05513

Q9GZQ8

1

phosphorylation

down-regulates activity

0.2

LC3B is phosphorylated at Thr-50 within the LDS by serine/threonine kinase (STK) 3 and STK4. Here, we identified LIR motifs in STK3 and atypical protein kinase Cζ (PKCζ) and never in mitosis A (NIMA)-related kinase 9 (NEK9). All three kinases phosphorylated LC3B Thr-50 in vitro A phospho-mimicking substitution of Thr-50 impaired binding of several LIR-containing proteins, such as ATG4B, FYVE, and coiled-coil domain-containing 1 (FYCO1), and autophagy cargo receptors p62/sequestosome 1 (SQSTM1) and neighbor of BRCA1 gene (NBR1).

SIGNOR-273906

P04637

P48730

0

phosphorylation

up-regulates

0.578

Here we show that the direct association between a p53 n-terminal peptide and mdm2 is disrupted by phosphorylation of the peptide on thr(18) but not by phosphorylation at other n-terminal sites, including ser(15) and ser(37). Thr(18) was phosphorylated in vitro by casein kinase (ck1).

SIGNOR-75889

Q5T3J3

Q96T88

0

ubiquitination

down-regulates activity

0.2

In our study, we found the UHRF1 is sufficient to suppress RIF1 accumulation at DSBs in S phase and CtIP functions as a negative regulator of RIF1 only in G2 phase (XREF_FIG; XREF_SUPPLEMENTARY).|UHRF1 ubiquitinates RIF1.

SIGNOR-278604

Q9Y5X2

O14920

2

binding

up-regulates activity

0.2

IFNγ induced JAK1-mediated phosphorylation of SNX8 at Tyr95 and Tyr126, which promoted the recruitment of IKKβ to the JAK1 complex.

SIGNOR-273646

Q9NYJ8

Q13546

2

binding

up-regulates activity

0.864

TNF_ induced the polyubiquitination of RIP and the association of polyubiquitinated RIP with TAB2.

SIGNOR-128406

P17542

P25800

2

binding

up-regulates

0.736

Transcriptional activity of tal1 in t cell acute lymphoblastic leukemia (t-all) requires rbtn1 or -2

SIGNOR-46114

O95644

Q13627

0

phosphorylation

up-regulates activity

0.429

DYRK1A phosphorylation of NFATc1 and alphaA at S261, S278, S403 and S409 interfered with NFATc1 ubiquitination and ubiquitin-proteasome degradation.|Here, we demonstrated that DYRK1A increased NFATc1 (NFATc1 and alphaA isoform) protein stability, in contrast to the decrease of NFATc2 protein stability by DYRK1A.

SIGNOR-278278

Q99835

P08754

2

binding

up-regulates

0.429

Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling.

SIGNOR-199165

Q13153

P17600

1

phosphorylation

up-regulates activity

0.349

Synapsin I is phosphorylated at Ser603 by p21-activated kinases. the Ser603 residue must be one of the pivotal sites for the release

SIGNOR-250235

P01116

Q8N431

2

binding

up-regulates

0.2

Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.

SIGNOR-161508

O95837

P41146

2

binding

up-regulates activity

0.353

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-257209

P22415

P78347

2

binding

up-regulates activity

0.489

TFII-I has been shown to interact with USF and to associate with either E-box elements or initiator sequences to activate gene transcription

SIGNOR-268538

P51955

Q8N137

1

phosphorylation

down-regulates activity

0.35

The opposite outcomes in NEK2- and centrobin-depleted cells suggest that NEK2 antagonizes biological functions of centrobin.|These results suggest that NEK2 phosphorylates specific sites of centrobin, which are distinct from the PLK1 phosphorylation sites.

SIGNOR-279545

P17861

P60900

2

binding

down-regulates quantity by destabilization

0.303

We saw preferential binding of XBP-1u to subunits _5, _6 and _7.2. We demonstrate that XBP-1u undergoes efficient degradation in vitro by 20S proteasomes in the absence of ubiquitination.

SIGNOR-239039

P25445

Q99683

2

binding

up-regulates

0.694

Ask1 binds fas

SIGNOR-109676

P78509

O15409

0

transcriptional regulation

up-regulates quantity by expression

0.365

By interacting with CASK, TBR1 regulates several ASD candidate genes, such as GRIN2B, AUTS2 and RELN—all of which are recurrently mutated in ASD. In areas of the brain with overlapping expression patterns, such as in glutamatergic layer 6 neurons, the TBR1–FOXP2 interaction may result in co-ordinated regulation of common downstream targets.

SIGNOR-266833

P29474

P07900

2

binding

up-regulates

0.76

The binding of hsp90 to enos enhances the activation of enos.

SIGNOR-57211

P04637

Q70YC5

1

transcriptional regulation

up-regulates quantity by expression

0.29

Here, analysis of p53-regulated genes activated in the setting of telomere dysfunction identified Zfp365 (ZNF365 in humans) as a direct p53 target that promotes genome stability| Our study identified ZNF365 as a necessary target whose activation by p53 in the presence of critically short telomeres contributes to genomic stability. We provide evidence that loss of ZNF365 leads to increased expression of CFS and dysfunctional telomeres, aberrant sister telomere recombination, and increased aneuploidy

SIGNOR-272476

Q8N5U6

P50222

2

binding

up-regulates activity

0.375

RFN10 co-immunoprecipitates with MEOX2. RNF10 potentiates MEOX2 transcriptional activation

SIGNOR-236968

Q9UK99

Q13501

2

binding

down-regulates quantity by destabilization

0.2

F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation. Here we show that another F-box protein Fbxo3, belonging to the FBXO type protein family, also interacts with and targets Smurf1 for poly-ubiquitination and proteasomal degradation. The SCF complex is composed of F-box protein, Skp1, Cullin1 (Cul1) and ROC1. Fbxo3, whose substrates are few, forms SCF Fbxo3 ubiquitin ligase and regulates the degradations of Fbxl2, p62, HIPK2 and p300 through the ubiquitin-proteasome pathway.

SIGNOR-272444

Q15208

O14980

1

phosphorylation

up-regulates activity

0.2

We further uncover that STK38 modulates XPO1 export activity by phosphorylating XPO1 on serine 1055, thus regulating its own nuclear exit.

SIGNOR-277483

Q01105

P48736

0

phosphorylation

up-regulates activity

0.336

We show that PI3Kgamma phosphorylates I2PP2A on serine 9 and 93 residues resulting in enhanced interaction of I2PP2A with PP2A.

SIGNOR-278320

P31749

O95988

2

binding

up-regulates

0.671

In vivo, tcl1 forms trimers, which associate with akt. Tcl1 facilitates the oligomerization and activation of akt. Our data show that tcl1 is a novel akt kinase coactivator, which promotes akt-induced cell survival and proliferation.

SIGNOR-81713

Q8IZP0

P06493

0

phosphorylation

down-regulates activity

0.419

We identified serine 216 of Abi1 as a target of CDK1/cyclin B kinase that is phosphorylated in cells at the onset of mitosis.|Bcr-Abl-induced actin polymerization requires the Abi1 pathway, as the blockade of the signal transduction from Bcr-Abl to Abi1 abolishes the F-actin assembly|serine phosphorylation of Abi1 by CDK1/cyclin B serves as a cell cycle-dependent regulatory mechanism that inhibits actin assembly

SIGNOR-264421

P16949

P45984

0

phosphorylation

down-regulates

0.256

Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. Here we show that in response to hyperosmotic stress, jnk phosphorylates a key cytoplasmic microtubule regulatory protein, stathmin (stmn), on conserved ser-25 and ser-38 residues. In in vitro biochemical studies, we identified stmn ser-38 as the critical residue required for efficient phosphorylation by jnk and identified a novel kinase interaction domain in stmn required for recognition by jnk. We revealed that jnk was required for microtubule stabilization in response to hyperosmotic stress.

SIGNOR-166698

P17612

O95295

1

phosphorylation

up-regulates activity

0.307

PKA-phosphorylation of Snapin significantly increases its binding to synaptosomal-associated protein-25 (SNAP-25). Mutation of Snapin serine 50 to aspartic acid (S50D) mimics this effect of PKA phosphorylation

SIGNOR-250053

Q05209

Q9Y6E0

0

phosphorylation

down-regulates activity

0.272

In addition, MST3 can phosphorylate PTP-PEST and inhibit the tyrosine phosphatase activity of PTP-PEST.|MST3 directly phosphorylates and inactivates protein tyrosine phosphatase PTP-PEST, which enhances cell migration by enhancing the tyrosine phosphorylation of paxillin Y31 and Y118 [ ].

SIGNOR-279127

P23769

P10827

2

binding

down-regulates activity

0.2

We found that the T3-bound TR inhibits this reporter construct driven by GATA2 alone, indicating that the target of T3-bound TR repression is GATA2.

SIGNOR-267257

Q92831

Q00987

0

ubiquitination

down-regulates quantity by destabilization

0.621

Consistently, overexpression of MDM2 in p53 null cells caused the reduction of the protein level of PCAF, but not the mRNA level.|MDM2 ubiquitinated PCAF in vitro and in cells.

SIGNOR-278825

Q9HC97

P63096

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-256717

Q9NRY6

Q05655

0

phosphorylation

up-regulates

0.457

Ad198-activated pkc-delta induces phosphorylation of mitochondrial pls3 at thr21;pls3 is a critical downstream effector of pkc-delta in ad198-induced apoptosis.

SIGNOR-140759

P28358

P09429

2

binding

up-regulates activity

0.292

We show that HMG1 interacts with proteins encoded by the HOX gene family by establishing protein-protein contacts between the HMG box domains and the HOX homeodomain. HMG1 enhances, in a dose-dependent fashion, the sequence-specific DNA binding activity in vitro, and the transcriptional activation in a co-transfection assay in vivo, of the HOXD9 protein.

SIGNOR-240556

Q96J02

Q7Z434

1

ubiquitination

down-regulates quantity by destabilization

0.646

These data collectively indicate that AIP4 is the E3 ligase for MAVS.|We generated single substitutions (K362A, K371A or K420A) and combined point substitutions of MAVS and tested their degradation. K371A or K420A MAVS showed partial resistance to PCBP2-induced degradation (data not shown), whereas MAVS with the combined substitutions K371A and K420A (KK-AA) completely withstood the degradation

SIGNOR-260362

P43405

Q8N884

1

phosphorylation

up-regulates activity

0.2

Mechanistically, viral infection or foreign DNA transfection triggers recruitment of the spleen tyrosine kinase (SYK) and cGAS to the endosomal vacuolar H+ pump (V-ATPase), where SYK is activated and then phosphorylates human cGASY214/215 (mouse cGasY200/201) to prime its activation.

SIGNOR-277844

Q9UQB3

P22223

2

binding

up-regulates quantity by stabilization

0.294

To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member.

SIGNOR-252130

P32238

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-257236

Q02156

Q9H9S0

1

phosphorylation

up-regulates activity

0.329

Taken together, our results demonstrate that PKC\u03b5-mediated phosphorylation at T200 and T280 enhances Nanog protein stability in head and neck squamous cell carcinoma.|These observations confirm that PKCepsilon modulates Nanog transcriptional activity and demonstrate that Nanog is phosphorylated by PKCepsilon at T200 and T280 in vivo.

SIGNOR-278203

Q14938

P54756

1

transcriptional regulation

up-regulates quantity

0.2

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

SIGNOR-268909

Q6UWZ7

Q13315

0

phosphorylation

up-regulates activity

0.2

In this study, we demonstrate that ionizing radiation (IR)-induces ATM-dependent phosphorylation of serine 404 (S404) next to the pSPxF motif. Crystal structures of BRCT/Abraxas show that phosphorylation of S404 is important for extensive interactions through the N-terminal sequence outside the pSPxF motif and leads to formation of a stable dimer.

SIGNOR-255587

Q14344

Q9Y2T6

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-256670

Q01726

P43250

0

phosphorylation

down-regulates activity

0.313

Overexpression of GRK6 Inhibits Agonist-Induced cAMP Production in HBL Human Melanoma Cells, without Affecting MC1R Gene Expression

SIGNOR-252389

Q9UKB1

Q9Y2X9

1

ubiquitination

down-regulates quantity by destabilization

0.2

E3 ligase the beta-transducin repeat-containing protein 2 (beta-TrCP2) governs the ubiquitination and degradation of ZNF281. In human CRC specimens, endogenous beta-TrCP2 were inversely correlated with ZNF281.

SIGNOR-264897

P49768

Q9NZ42

0

cleavage

up-regulates

0.959

Our data reveal a direct role of pen-2 in proteolytic cleavage of ps1 and a regulatory function of aph-1, in coordination with pen-2, in the biogenesis of the ps1 complex.

SIGNOR-97113

Q86UR1

A1X283

2

binding

up-regulates activity

0.347

Tks4 and Tks5 bind NoxA1 through their SH3 domains in a Rac-independent manner|NoxO1 is required for full Nox1 and Nox3 oxidase activity at least partially because of its role in the plasma membrane recruitment of the NoxA1 activator protein|Tks4 and Tks5 support Nox1- and Nox3-dependent ROS generation

SIGNOR-264707

P17612

P13807

1

phosphorylation

down-regulates activity

0.508

The results presented in this paper show that the phosphorylation of glycogen synthetase a by cyclic AMP-dependent protein kinase results in the phosphorylation of two distinct serines termed site-l and site-2, which account for 90% of the total phosphorylation

SIGNOR-253009

Q16665

Q9Y3V2

0

sumoylation

up-regulates

0.457

Rsume,_a small_rwd-containing protein, enhances sumo conjugation and stabilizes hif-1alpha during hypoxia

SIGNOR-158590

Q04912

P26927

2

binding

up-regulates

0.896

P185ron is a tyrosine kinase activated by msp

SIGNOR-31107

P24666

P29317

1

dephosphorylation

down-regulates activity

0.66

The SAM domain tyrosine Y960 which has been implicated in downstream PI3K signaling is dephosphorylated exclusively by HCPTP-B. The activation loop tyrosine (Y772) which directly controls kinase activity is dephosphorylated about six times faster by HCPTP-A. In contrast, the juxtamembrane tyrosines (Y575, Y588 and Y594) which are implicated in both control of kinase activity and downstream signaling are dephosphorylated by both variants with similar rates

SIGNOR-246023

P45984

P49768

1

phosphorylation

up-regulates

0.376

This jnk phosphorylation of ps1 at ser(319)thr(320) enhances the stability of the ps1 c-terminal fragment that is necessary for gamma-secretase activity.

SIGNOR-179676

Q00535

P35712

1

phosphorylation

down-regulates quantity

0.366

GST-Sox6 was phosphorylated in vitro by Cdk5 and p35 (XREF_FIG).|Inhibition of Cdk5 activity by DN Cdk5 and roscovitine increases the Sox6 expression in primary cortical neurons.

SIGNOR-279365

P30304

Q15208

0

phosphorylation

down-regulates quantity

0.247

Here, we demonstrate that the depletion of serine-threonine kinase 38 (STK38) prevents the DNA-damage-induced degradation of CDC25A and subsequent G2 arrest, and that STK38 directly phosphorylates CDC25A at Ser-76, resulting in CDC25A's degradation.

SIGNOR-279488