GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 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
Q9UHI6	P58012	1	binding	up-regulates	0.445	Dp103 further increased the cell killing effect induced by foxl2 probably due to the direct association of dp103 with foxl2 protein.	SIGNOR-140388
Q12955	O95166	1	binding	up-regulates activity	0.445	Importantly, the 480 kDa ankyrin-G isoform has also been shown to stabilize GABAergic synapses on the soma and AIS of excitatory pyramidal neurons by interacting with the GABAA receptor-associated protein (GABARAP) to inhibit GABAA receptor endocytosis	SIGNOR-266709
P52333	P35222	1	phosphorylation	up-regulates activity	0.444	Jak3 phosphorylates Tyr 30, Tyr 64, and Tyr 86 of beta-catenin in intestinal epithelial cells.	SIGNOR-278180
Q05209	P42768	1	dephosphorylation	down-regulates	0.444	Furthermore, we demonstrate that pstpip serves as a scaffold protein between ptp-pest and wasp and allows ptp-pest to dephosphorylate wasp. This finding suggests a possible mechanism for ptp-pest to directly modulate actin remodeling through the pstpip-wasp interaction.	SIGNOR-121136
Q9BYP7	Q9UHW9	1	phosphorylation	down-regulates activity	0.444	WNK3, which inhibits the activity of KCC3, promoted phosphorylation of Ser-96 as well as Thr-991 and Thr-1048.	SIGNOR-260912
Q9HC98	P52732	1	phosphorylation	up-regulates activity	0.444	Nek6 phosphorylated Eg5 at several sites in vitro and one of these sites, Ser1033, is phosphorylated in vivo during mitosis. Whereas CDK1 phosphorylates nearly all Eg5 at Thr926 during mitosis, Nek6 phosphorylates approximately 3% of Eg5, primarily at the spindle poles.	SIGNOR-273886
Q00987	P49757	2	ubiquitination	down-regulates	0.444	These data strongly suggest thatmdm2functions as the ubiquitin ligase toward hnumb and that it induces its degradation in intact cells.	SIGNOR-99497
Q8WY64	Q14114	1	ubiquitination	down-regulates quantity by destabilization	0.444	Here we demonstrate that Idol also targets two closely related LDLR family members, VLDLR and ApoE receptor 2 (ApoER2), proteins implicated in both neuronal development and lipid metabolism. Idol triggers ubiquitination of the VLDLR and ApoER2 on their cytoplasmic tails, leading to their degradation.	SIGNOR-271486
O15297	Q16539	1	dephosphorylation	down-regulates activity	0.444	Wip1 selectively inactivates p38 by specific dephosphorylation of its conserved threonine residue	SIGNOR-84793
Q15139	P22059	1	phosphorylation	down-regulates	0.444	Pkd attenuates the function of both cert and osbp by phosphorylation at their respective ser(132) and ser(240) residues (phosphorylation inhibition)	SIGNOR-171756
P35354	P05112	1	null	up-regulates	0.444	Cox2 Is a Direct Srf Target Gene and Controls Il4 Expression	SIGNOR-255967
P30968	P63092	1	binding	up-regulates activity	0.444	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 ‚â• -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 ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256792
P17612	O60825	1	phosphorylation	up-regulates activity	0.444	PFK-2 that was phosphorylated on Ser466, but not Ser483, by PKA did not bind to 14-3-3s‚	SIGNOR-250025
P12931	P15941	1	phosphorylation	up-regulates	0.444	The c-src tyrosine kinase regulates signaling of the human df3/muc1 carcinoma-associated antigen with gsk3 beta and betBeta-catenin c-src phosphorylates the muc1 cytoplasmic domain at a yekv motif c-src-mediated phosphorylation of muc1 increases binding of muc1 and betBeta-catenin	SIGNOR-85938
Q99933	O75807	1	null	down-regulates activity	0.444	Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions.\|BAG-1 negatively modulates GADD34-bound PP1 activity, and the expression of BAG-1 isoforms can also mask GADD34-mediated inhibition of colony formation and suppression of transcription. Our findings suggest that BAG-1 may function to suppress the GADD34-mediated cellular stress response and support a role for BAG-1 in the survival of cells undergoing stress.	SIGNOR-254117
P53350	Q6IBW4	1	phosphorylation	up-regulates activity	0.444	Plk1 phosphorylation of CAP-H2 at Ser288 is required for the accumulation of CAP-H2 and accurate chromosomal condensation during prophase.	SIGNOR-278419
P08311	P05546	1	cleavage	down-regulates activity	0.444	Amino acid sequence analysis led to the conclusion that both neutrophil elastase and cathepsin G cleave HC at Ile66, which does not affect HC activity, and at Val439, near the reactive site Leu444, which inactivates HC.	SIGNOR-256509
Q6N021	O15294	1	binding	up-regulates	0.444	Tet2 and tet3 associate with the o_glcnac transferase ogt / tet2 and tet3 promote ogt_mediated glcnacylation	SIGNOR-200695
P48546	P63092	1	binding	up-regulates activity	0.444	The GPCRs are allocated in five families where the GLP-1R and GIPR are found within the secretin family, also classified as class B [31,32]. Upon stimulation by an extracellular stimuli (ligand), GPCRs undergo conformational changes, and triggers downstream intracellular signals by coupling with G proteins (or other intracellular proteins such as arrestins), causing a wide range of both physiological and pathological processes.To stimulate insulin secretion, and in the presence of elevated blood glucose concentrations, GLP-1R activation in pancreatic beta cells promote recruitment and activation of Gαs protein leading to adenylate cyclase-mediated cAMP production, elevation of Ca2+, and ERK1/2 phosphorylation (Fig. 3)	SIGNOR-278138
P34969	P38405	1	binding	up-regulates activity	0.444	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-256926
P49757	Q00987	2	binding	down-regulates	0.444	Numb interacts with mdm2, and inhibits its ubiquitin-ligase function on tp53 (which in itself is inhibitory for tp53), thus numb activates (b) tp53	SIGNOR-168454
O95376	Q96P20	1	ubiquitination	up-regulates activity	0.444	ARIH2 can ubiquitinate NLRP3 via the NACHT domain of NLRP3, and the RING2 domain of ARIH2 is required for NLRP3 ubiquitination 65.\|Overexpression of ARIH2 promotes NLRP3 ubiquitination and inhibits NLRP3 inflammasome activation 65.	SIGNOR-278686
P53779	Q93045	1	phosphorylation	down-regulates	0.444	We demonstrate that purified scg10 can be phosphorylated by two subclasses of mitogen-activated protein (map) kinases, c-jun n-terminal/stress-activated protein kinase (jnk/sapk) and p38 map kinase;jnk3/sapkbeta phosphorylation occurs at ser-62 and ser-73, residues that result in reduced microtubule-destabilizing activity for scg10.	SIGNOR-112114
P49841	P48436	1	phosphorylation	down-regulates activity	0.444	(E) The SOX9 K2 domain is phosphorylated by GSK3\u03b2 at T236.\|Based on our findings that inhibition of GSK3\u03b2 prevents DNA damage-induced SOX9 degradation, and that FBW7 targets SOX9 for degradation after DNA damage, we reasoned that phosphorylation of SOX9 by GSK3\u03b2 is required for FBW7-mediated SOX9 degradation.	SIGNOR-279725
Q8IXJ9	P10276	1	binding	up-regulates activity	0.444	Therefore, ASXL1, a vertebrate PcG/TrxG protein, may mediate RA-regulated cell growth by modulating RAR activity.Finally, the ASXL1-induced accumulation of acetylated H3 may enhance the RAR-mediated transcriptional activity. In this study, we demonstrate that mammalian ASXL1 interacts with the AF-2 AD core of RAR (and RXR) through a novel, promiscuous NR box (LVMQLL) and enhances transcriptional activity of the receptors in certain cells.	SIGNOR-255910
O15297	Q13950	1	dephosphorylation	up-regulates activity	0.444	Activating dephosphorylation of RUNX2 by Wip1 increases its transcriptional activity on the Bax promoter.	SIGNOR-277110
P53350	Q00613	1	phosphorylation	down-regulates	0.444	Hsf1 was phosphorylated by plk1 at ser(216) of the dsgxxs motif during the timing of mitosis and a phospho-defective mutant form of hsf1 inhibited mitotic progression. Phosphorylated hsf1 during spindle pole localization underwent ubiquitin degradation through the scf(beta-trcp) pathway.	SIGNOR-180915
P62136	P27361	1	dephosphorylation	down-regulates	0.444	P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3). the dual specificity phosphatases that specifically dephosphorylate and inactivate the p-erk1/2 are called mapk phosphatases	SIGNOR-103155
Q9Y577	Q07820	1	polyubiquitination	down-regulates quantity by destabilization	0.444	Here, we identified Trim17 as a novel E3 ubiquitin-ligase for Mcl-1. Indeed, Trim17 co-immunoprecipitated with Mcl-1. Trim17 ubiquitinated Mcl-1 in vitro. Overexpression of Trim17 decreased the protein level of Mcl-1 in a phosphorylation- and proteasome-dependent manner. Finally, knock down of Trim17 expression reduced both ubiquitination and degradation of Mcl-1 in neurons.	SIGNOR-272032
O14559	P63000	1	gtpase-activating protein	down-regulates activity	0.444	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-260491
Q92630	O14746	1	phosphorylation	down-regulates activity	0.444	Dyrk2 phosphorylates TERT protein, a catalytic subunit of telomerase.\|In this study, we found that dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 2 (Dyrk2) negatively regulates telomerase activity.	SIGNOR-279611
Q00526	P05412	1	phosphorylation	up-regulates	0.443	Egf-induced cdk3 activation caused c-jun phosphorylation at ser63 and ser73, resulting in increased ap-1 transactivation.	SIGNOR-183013
Q13315	O75150	1	phosphorylation	up-regulates	0.443	E3 ubiquitin ligase, a heterodimeric complex of the ringfinger rfn20/rfn40 is phosphorylated by atm.	SIGNOR-175003
P18031	Q16539	1	dephosphorylation	down-regulates activity	0.443	Here, we show that PTP1B regulates CD40 and BAFF-R signaling and dephosphorylates the mitogen-activated protein kinase p38.\|Specifically, PTP1B counteracts p38 mitogen-activated protein kinase activation by directly dephosphorylating Tyr182 of this kinase.	SIGNOR-277167
Q8TF42	P22681	1	binding	down-regulates	0.443	Sts-1 and sts-2 contain sh3 domains that interacted with cbl, ub-associated domains, which bound directly to mono-ub or to the egfr/ub chimera as well as phosphoglycerate mutase domains that mediated oligomerization of sts-1/2. Ligand-induced recruitment of sts-1/sts-2 into activated egfr complexes led to inhibition of receptor internalization, reduction in the number of egfr-containing endocytic vesicles, and subsequent block of receptor degradation followed by prolonged activation of mitogenic signaling pathways.	SIGNOR-124897
P68400	Q04206	1	phosphorylation	up-regulates activity	0.443	We demonstrate that casein kinase II (CKII) interacts with p65 in vivo and can phosphorylate p65 at serine 529 in vitro. A CKII inhibitor (PD144795) inhibited TNFalpha-induced p65 phosphorylation in vivo. Furthermore, our results indicate that the association between IkappaBalpha and p65 inhibits p65 phosphorylation by CKII and that degradation of IkappaBalpha allows CKII to phosphorylate p65 to increase NF-kappaB transactivation potential.	SIGNOR-250942
Q00526	P06400	1	phosphorylation	down-regulates	0.443	The active form of prb is underphosphorylated. Cdk3/cyclin-c-mediated phosphorylation at ser-807 and ser-811 is required for g0-g1 transition.	SIGNOR-124212
P15976	P23769	1	transcriptional regulation	down-regulates quantity by repression	0.443	GATA-2 induces the expression of GATA-1, which first activates its cofactor FOG-1, and then downregulates GATA-2 cooperatively with FOG-1.	SIGNOR-256060
P04637	P35232	1	binding	up-regulates activity	0.443	Our previous studies have shown that prohibitin physically interacts with the marked-box domain of E2F family members and represses their transcriptional activity; in contrast, prohibitin could bind to and enhance the transcriptional activity of p53.	SIGNOR-268978
P14618	P40763	1	phosphorylation	up-regulates activity	0.443	PKM2 activates transcription of MEK5 by phosphorylating stat3 at Y705. In vitro phosphorylation assays show that PKM2 is a protein kinase using PEP as a phosphate donor	SIGNOR-267716
O15084	P36873	1	binding	up-regulates activity	0.443	Phosphatase Interactor Targeting K protein (PITK) was previously identified as a novel PP1 targeting subunit implicated in modulating the phosphorylation of the transcriptional regulator heterogeneous nuclear ribonucleoprotein K (hnRNP K)	SIGNOR-264794
Q6ZMQ8	Q15078	1	binding	up-regulates	0.443	Apoptosis-associated tyrosine kinase is a cdk5 activator p35 binding protein.	SIGNOR-118403
Q9UKB1	O14920	1	binding	down-regulates quantity by destabilization	0.443	We identified a human F-box/WD40 repeats protein (HOS), which is homologous to Slimb/h betaTrCP. Being a part of SCF complex with Skp1 and Cullin1, HOS specifically interacted with the phosphorylated IkappaB and beta-catenin, targeting these proteins for proteasome-dependent degradation in vivo.	SIGNOR-272544
Q00535	Q13224	1	phosphorylation	down-regulates quantity	0.443	Cdk5 phosphorylates NR2B at Ser1116 and controls surface level expression.\|Reduction in Cdk5 activity, as well as disruption of Cdk5-NR2B interactions consistently increased NR2B surface levels and facilitated NMDA mediated synaptic function.	SIGNOR-278265
O43151	O15294	1	binding	up-regulates	0.443	Tet2 and tet3 associate with the o_glcnac transferase ogt / tet2 and tet3 promote ogt_mediated glcnacylation	SIGNOR-200729
P12931	Q13936	1	phosphorylation	up-regulates activity	0.443	Cotransfection of human embryonic kidney (HEK)-293 cells with hCa(v)1.2b and c-Src resulted in tyrosine phosphorylation of the calcium channel, which was prevented by nitration of tyrosine residues by peroxynitrite. Whole cell calcium currents were reduced by 58 + 5% by the Src kinase inhibitor PP2 and 64 + 6% by peroxynitrite.	SIGNOR-276081
P27361	P36956	1	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
P29323	Q13224	1	phosphorylation	up-regulates quantity	0.443	In addition, EPHB2 signaling leads to phosphorylation of GluN2B at tyrosine residue 1472 preventing clathrin dependent endocytosis, and increasing the surface retention of GluN2B containing NMDARs.	SIGNOR-279710
P54646	O60825	1	phosphorylation	up-regulates activity	0.443	AMPK phosphorylates and activates heart PFK-2 in vitro and in intact cells. activation of PFK-2 was due to the phosphorylation of Ser466	SIGNOR-250323
Q96Q27	P21333	1	polyubiquitination	down-regulates quantity by destabilization	0.442	ASB2 is the specificity subunit of an E3 ubiquitin ligase complex and is proposed to exert its effects by regulating the turnover of specific proteins; however, no ASB2 substrates had been identified. Here, we report that ASB2 targets the actin-binding proteins filamin A and B for proteasomal degradation.	SIGNOR-271740
P68400	P08575	1	phosphorylation	up-regulates	0.442	Mutational analysis of ck2 consensus sites showed that the target for ck2 was in an acidic insert of 19 amino acids in the d2 domain, and ser to ala mutations at amino acids 965, 968, 969, and 973 abrogated ck2 phosphorylation of cd45. Ck2 phosphorylation increased cd45 activity 3-fold toward phosphorylated myelin basic protein,	SIGNOR-65277
P06213	P60484	1	phosphorylation	down-regulates activity	0.442	Our results show that the kinase region of IRβ subunit physically binds to PTEN and phosphorylates on Y27 and Y174. In the current study, we discovered that IR also downregulates PTEN through tyrosine phosphorylation and suggest that Y27 and 174 are the two key tyrosines.	SIGNOR-276470
P62324	P17482	1	binding	up-regulates activity	0.442	The leukemia-associated protein Btg1 and the p53-regulated protein Btg2 interact with the homeoprotein Hoxb9 and enhance its transcriptional activation.	SIGNOR-221019
P17252	P19086	1	phosphorylation	up-regulates	0.442	Functional role of amino-terminal serine16 and serine27 of g alphaz in receptor and effector coupling.	SIGNOR-48681
Q96BR1	P49841	1	phosphorylation	down-regulates activity	0.442	Phosphorylation of GSK3 by PKB or SGK1 inhibits GSK3 activity\|estern blotting using an antibody specific for the PKB/SGK1 consensus phosphorylation site in GSK3a/beta (serine 21 and 9 respectively) revealed an increase in GSK3a/beta phosphorylation in human embryonic kidney 293 (HEK293) cells overexpressing wild type SGK1, constitutively active SGK1, but not catalytically inactive SGK1.\|The effect of SGK1 was mimicked by PKB and SGK3.	SIGNOR-249167
Q8IYK4	P02452	1	glycosylation	up-regulates activity	0.442	Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.	SIGNOR-261156
P05186	P10451	1	dephosphorylation	down-regulates activity	0.442	This result suggests that endogenous mouse TNAP dephosphorylates OPN in osteoblasts and that overexpressed human TNAP dephosphorylates OPN, compensating for the lack of endogenous TNAP in [Col1a1-Tnap +/\u2212 ;Alpl \u2212/\u2212 ] cells.	SIGNOR-277045
P68871	Q86VB7	1	binding	up-regulates activity	0.442	These data suggest that hemoglobin may mediate a stimulatory effect on erythropoiesis through the activation of CD163 on hematopoietic progenitor cells.	SIGNOR-251746
P04626	P49327	1	phosphorylation	up-regulates activity	0.442	Conversely, HER2 directly phosphorylates and activates FASN, while it also promotes FASN gene expression ( xref ; xref ).\|Conversely, HER2 directly phosphorylates and activates FASN, while it also promotes FASN gene expression.	SIGNOR-278399
Q12923	P25963	1	dephosphorylation	up-regulates quantity by stabilization	0.442	Identification of IkappaBalpha as a substrate of Fas-associated phosphatase-1\|A full-length FAP-1 protein preferentially dephosphorylates Tyr-42 of IkBa\|Moreover, other studies have shown that tyrosine phosphorylation of IkBa on Tyr-42 (which occurs with Fas ligand binging) protected against inducible degradation both in vitro [30] and in vivo [38]	SIGNOR-248712
O14965	Q9UPY8	1	phosphorylation	up-regulates	0.442	Aurora-a and aurora-b phosphorylate eb3 at ser-176 in a spatial and cell cycle-specific manner, respectively during mitosis two kinases, aurora-a and aurora-b, phosphorylate eb3 at ser-176, and the resulting phosphorylation disrupts the eb3-siah-1 complex. Indeed, eb3 is stabilized during mitosis and facilitates cell cycle progression.	SIGNOR-187657
P01148	P18146	1	binding	up-regulates activity	0.442	EGR1 bound to two binding sites on the LHB promoter and this binding was increased by GNRH1. Mutation of either site or knockdown of endogenous EGR1 decreased basal and/or GNRH1-regulated promoter activity.	SIGNOR-254918
P19419	P17252	1	transcriptional regulation	up-regulates quantity by expression	0.442	The luciferase reporter assay results revealed that the presence of both MZF-1 and Elk-1 significantly contributed to the upregulation of PKCα gene transcription activity.	SIGNOR-256336
O15013	P63000	1	guanine nucleotide exchange factor	up-regulates activity	0.442	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-260536
O95071	Q8IYW5	1	ubiquitination	down-regulates quantity	0.442	Here, we show that TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage. We find that RNF168 can be saturated by increasing amounts of DSBs. Depletion of TRIP12 and UBR5 allows accumulation of RNF168 to supraphysiological levels, followed by massive spreading of ubiquitin conjugates and hyperaccumulation of ubiquitin-regulated genome caretakers such as 53BP1 and BRCA1.	SIGNOR-266782
P54821	P11831	1	binding	up-regulates	0.442	The human homeodomain proteinphox1interacts functionally with serum response factor (srf) to impart serum responsive transcriptional activity to srf-binding sites in a hela cell cotransfection assay.	SIGNOR-52657
Q9Y6E0	Q9Y2H1	1	phosphorylation	up-regulates	0.441	Ndr1/ndr2 protein kinase is activated by phosphorylation on the activation loop phosphorylation site ser281/ser282 and the hydrophobic motif phosphorylation site thr444/thr442. Autophosphorylation of ndr is responsible for phosphorylation on ser281/ser282, whereas thr444/thr442 is targeted by an upstream kinase. Here we show that mst3, a mammalian ste20-like protein kinase, is able to phosphorylate ndr protein kinase at thr444/thr442. In vitro, mst3 selectively phosphorylated thr442 of ndr2, resulting in a 10-fold stimulation of ndr activity.	SIGNOR-142510
O00255	Q9BXW9	1	binding	up-regulates	0.441	Menin interacts with fancd2 / loss of menin expression in mouse embryonic fibroblasts leads to increased sensitivity to dna damage. Furthermore, menin is localized to chromatin and nuclear matrix, and the association with nuclear matrix is enhanced by gamma-irradiation. Together, these results suggest that menin plays a critical role in repair of dna damage in concert with fancd2.	SIGNOR-103947
Q14164	Q9NQC7	1	phosphorylation	down-regulates activity	0.441	CYLD is phosphorylated by IKK\u03b5 at Ser418.\|Together, these observations demonstrate that I\u03baB kinase\u03b5-mediated phosphorylation of CYLD at Ser418 inhibits CYLD deubiquitinase activity.	SIGNOR-278311
P53350	P36956	1	phosphorylation	up-regulates activity	0.441	As illustrated in , the turnover of nuclear SREBP1a was attenuated in the presence of Plk1, confirming that Plk1 stabilizes nuclear SREBP1 by reducing its degradation.\|Figure 2.Plk1 phosphorylates threonine 424, serine 467 and serine 486 in nuclear SREBP1 during mitosis. (A) In vitro kinase assay with recombinant nuclear SREBP1a and Plk1.	SIGNOR-279382
P28482	P07101	1	phosphorylation	up-regulates	0.441	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 hydroxylase in vitro at comparable rates to other proteins thought to be physiological substrates of these protein kinases.The effect on activity of phosphorylating both ser31 and ser40 was not additive. The possible roles of mapkap kinase-1, mapkap kinase-2 and map kinase in the regulation of tyrosine hydroxylase in vivo are discussed.	SIGNOR-34674
Q9UK97	Q9Y4R8	1	binding	down-regulates quantity by destabilization	0.441	Here we report that Tel2 and Tti1 are targeted for degradation within mTORC1 by the SCFFbxo9 ubiquitin ligase to adjust mTOR signalling to growth factor availability. The interaction between Tel2/Tti1 and Fbxo9 identified by mass spectrometry suggests that SCFFbxo9 is probably the ubiquitin ligase that mediates degradation of both proteins.	SIGNOR-271996
P38398	Q03468	1	polyubiquitination	down-regulates quantity by destabilization	0.441	BRCA1 polyubiquitinates CSB and this polyubiquitination and subsequent degradation of CSB occur following UV irradiation, even in the absence of Cockayne syndrome A (CSA) protein.	SIGNOR-272754
P60484	Q99801	1	dephosphorylation	up-regulates quantity by stabilization	0.441	Loss of PTEN Accelerates NKX3.1 Degradation to Promote Prostate Cancer Progression.\|PTEN was also able to dephosphorylate NKX3.1 at threonine 179, a target of protein kinase C, but not threonine residues 89 and 93, targeted by casein kinase 2 .	SIGNOR-277026
Q9UKB1	O15111	1	binding	down-regulates quantity by destabilization	0.441	We identified a human F-box/WD40 repeats protein (HOS), which is homologous to Slimb/h betaTrCP. Being a part of SCF complex with Skp1 and Cullin1, HOS specifically interacted with the phosphorylated IkappaB and beta-catenin, targeting these proteins for proteasome-dependent degradation in vivo.	SIGNOR-272545
P05771	P14679	1	phosphorylation	up-regulates	0.441	We conclude that pkc-beta activates tyrosinase directly by phosphorylating serine residues at positions 505 and 509 in the cytoplasmic domain of this melanosome-associated protein. our results strongly suggest that direct phosphorylation of tyrosinase by pkc-_ leads to its activation.	SIGNOR-67870
O14519	P24941	1	binding	down-regulates activity	0.441	The ubiquitously expressed CDK2AP1 protein is the only known specific inhibitor of CDK2, making it an important component of cell cycle regulation during G1-to-S phase transition.	SIGNOR-264781
Q96EB6	O15105	1	deacetylation	down-regulates	0.441	Sirt1 reversed acetyl-transferase (p300)-mediated acetylation of two lysine residues (lys-64 and -70) on smad7. sirt1-mediated deacetylation of smad7 enhanced smad ubiquitination regulatory factor 1 (smurf1)-mediated ubiquitin proteasome degradation, which contributed to the low expression of smad7 in sirt1-overexpressing mesangial cells.	SIGNOR-150595
Q03164	P17947	1	methylation	up-regulates quantity by expression	0.441	Furthermore, we show that both MLL and AML1/CBFβ are required for maintaining the H3K4-me3 mark at the PU.1 upstream regulatory element (URE) and promoter region, and for full PU.1 gene expression.	SIGNOR-255874
P17252	Q15139	1	phosphorylation	up-regulates	0.441	These results provide direct evidence that pkd becomes activated in vivo as a consequence of pkc-mediated phosphorylation of serines 744 and 748.	SIGNOR-66666
Q9UNE7	P54253	1	ubiquitination	down-regulates quantity by destabilization	0.441	CHIP protects from the neurotoxicity of expanded and wild-type ataxin-1 and promotes their ubiquitination and degradation\|Interestingly, CHIP also interacts with and ubiquitinates unexpanded ataxin-1	SIGNOR-278666
P19484	P11279	1	transcriptional regulation	up-regulates quantity by expression	0.441	Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy\|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1\|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants	SIGNOR-276555
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
P00519	P78352	1	phosphorylation	up-regulates activity	0.441	Moreover, c-Abl phosphorylates PSD-95 at tyrosine 533.\|c-Abl modulates the synaptic contact number and PSD-95 clustering.	SIGNOR-278391
P60484	P23528	1	dephosphorylation	up-regulates activity	0.441	Unexpectedly, cofilin-1 activation by PGE 2 was mediated by the protein phosphatase activity of PTEN (phosphatase and tensin homolog deleted on chromosome 10), with which it directly associated.\|Unexpectedly, cofilin-1 dephosphorylation and activation in our model was mediated by the protein phosphatase activity of PTEN.	SIGNOR-276980
O00253	Q01718	1	binding	down-regulates activity	0.441	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 α, β, and γ melanocyte–stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins	SIGNOR-268696
P00533	O00750	1	phosphorylation	up-regulates	0.44	The n-terminal region of pi3k-c2beta was found to selectively interact with the egf receptor in vitro, suggesting that it mediates the association of this pi3k with the receptor.	SIGNOR-77195
Q96CN5	Q5TZA2	1	binding	up-regulates activity	0.44	Here, we show that LRRC45 is a centrosome linker that localizes at the proximal ends of the centrioles and forms fiber-like structures between them. Depletion of LRRC45 results in centrosome splitting during interphase. LRRC45 interacts with C-Nap1 and rootletin	SIGNOR-273704
Q02156	P17302	1	phosphorylation	down-regulates activity	0.44	Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication.\|These data strongly suggest that PKC directly phosphorylates Cx43 on S368 in vivo, which results in a change in single channel behavior that contributes to a decrease in intercellular communication.	SIGNOR-144465
Q9UM73	Q92529	1	phosphorylation	up-regulates	0.44	Anaplastic lymphoma kinase (alk), which turned out to be one of these phosphoproteins, was constitutively activated and associated with the ptb domain of shcc in three neuroblastoma cells. In vitro kinase assay revealed that shcc is a potent substrate of the activated alk kinase. The alk gene locus was significantly amplified in both of these cell lines, suggesting that gene amplification leads to constitutive activation of the alk kinase, which results in hyperphosphorylation of shcc.	SIGNOR-91537
Q9BY84	Q9UQF2	1	binding	up-regulates	0.44	Here we report that jip-1 also binds the dual-specificity phosphatases mkp7 and m3/6 via a region independent of its jnk binding domain. when mkp7 is bound to jip-1 it reduces jnk activation leading to reduced phosphorylation of the jnk target c-jun	SIGNOR-97173
O00222	P63092	1	binding	up-regulates activity	0.44	MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.	SIGNOR-264081
P47901	P63092	1	binding	up-regulates activity	0.44	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 ‚â• -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 ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256791
P31749	O75030	1	phosphorylation	down-regulates quantity by destabilization	0.44	We found that AKT phosphorylates MITF at S510. Phosphorylated MITF S510 enhances its affinity to TP53 and promotes CDKN1A expression. Phosphorylation of MITF by AKT induces its degradation	SIGNOR-277281
O00253	Q01726	1	binding	down-regulates activity	0.44	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-268699
O43353	O14733	1	phosphorylation	up-regulates activity	0.44	Collectively, the results suggest that RIPK2 binds to and activates MKK7.\|Radioactive in vitro kinase assay showed that RIPK2 can directly phosphorylate kinase-dead (K149A) MKK7 (Fig.\u00a0 xref ).	SIGNOR-280105
O15294	Q8NFU7	1	glycosylation	up-regulates activity	0.44	The DNA demethylation enzyme Tet1 interacts with Ogt and is O-GlcNAcylated. Tet1 protein stability is positively regulated by O-GlcNAcylation, and its repression function on targeting genes is dependent on Ogt.	SIGNOR-259184
P53701	P99999	1	chemical modification	up-regulates activity	0.44	Cytochrome c oxidase catalyzes the reduction of molecular oxygen to water, a process in which four electrons, four protons, and one molecule of oxygen are consumed. The reaction is coupled to the pumping of four additional protons across the membrane. According to the currently accepted concept, the pumping of all four protons occurs after the binding of oxygen to the reduced enzyme and is exclusively coupled to the last two electron transfer steps.	SIGNOR-280296
P53350	Q76N32	1	phosphorylation	down-regulates quantity by destabilization	0.44	We show that the intercentrosomal linker protein Cep68 is degraded in prometaphase through the SCF(βTrCP) (Skp1-Cul1-F-box protein) ubiquitin ligase complex. Cep68 degradation is initiated by PLK1 phosphorylation of Cep68 on Ser 332, allowing recognition by βTrCP.	SIGNOR-275621
Q00535	P56817	1	phosphorylation	up-regulates activity	0.44	BACE1 is phosphorylated by p25 and Cdk5 at Thr252.\|Our finding that p25/Cdk5 stimulates BACE1 activity supports that p25/Cdk5 may represent a promising target for the development of drugs to treat Alzheimer's disease.	SIGNOR-278249

Q9UHI6

P58012

1

binding

up-regulates

0.445

Dp103 further increased the cell killing effect induced by foxl2 probably due to the direct association of dp103 with foxl2 protein.

SIGNOR-140388

Q12955

O95166

1

binding

up-regulates activity

0.445

Importantly, the 480 kDa ankyrin-G isoform has also been shown to stabilize GABAergic synapses on the soma and AIS of excitatory pyramidal neurons by interacting with the GABAA receptor-associated protein (GABARAP) to inhibit GABAA receptor endocytosis

SIGNOR-266709

P52333

P35222

1

phosphorylation

up-regulates activity

0.444

Jak3 phosphorylates Tyr 30, Tyr 64, and Tyr 86 of beta-catenin in intestinal epithelial cells.

SIGNOR-278180

Q05209

P42768

1

dephosphorylation

down-regulates

0.444

Furthermore, we demonstrate that pstpip serves as a scaffold protein between ptp-pest and wasp and allows ptp-pest to dephosphorylate wasp. This finding suggests a possible mechanism for ptp-pest to directly modulate actin remodeling through the pstpip-wasp interaction.

SIGNOR-121136

Q9BYP7

Q9UHW9

1

phosphorylation

down-regulates activity

0.444

WNK3, which inhibits the activity of KCC3, promoted phosphorylation of Ser-96 as well as Thr-991 and Thr-1048.

SIGNOR-260912

Q9HC98

P52732

1

phosphorylation

up-regulates activity

0.444

Nek6 phosphorylated Eg5 at several sites in vitro and one of these sites, Ser1033, is phosphorylated in vivo during mitosis. Whereas CDK1 phosphorylates nearly all Eg5 at Thr926 during mitosis, Nek6 phosphorylates approximately 3% of Eg5, primarily at the spindle poles.

SIGNOR-273886

Q00987

P49757

2

ubiquitination

down-regulates

0.444

These data strongly suggest thatmdm2functions as the ubiquitin ligase toward hnumb and that it induces its degradation in intact cells.

SIGNOR-99497

Q8WY64

Q14114

1

ubiquitination

down-regulates quantity by destabilization

0.444

Here we demonstrate that Idol also targets two closely related LDLR family members, VLDLR and ApoE receptor 2 (ApoER2), proteins implicated in both neuronal development and lipid metabolism. Idol triggers ubiquitination of the VLDLR and ApoER2 on their cytoplasmic tails, leading to their degradation.

SIGNOR-271486

O15297

Q16539

1

dephosphorylation

down-regulates activity

0.444

Wip1 selectively inactivates p38 by specific dephosphorylation of its conserved threonine residue

SIGNOR-84793

Q15139

P22059

1

phosphorylation

down-regulates

0.444

Pkd attenuates the function of both cert and osbp by phosphorylation at their respective ser(132) and ser(240) residues (phosphorylation inhibition)

SIGNOR-171756

P35354

P05112

1

null

up-regulates

0.444

Cox2 Is a Direct Srf Target Gene and Controls Il4 Expression

SIGNOR-255967

P30968

P63092

1

binding

up-regulates activity

0.444

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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256792

P17612

O60825

1

phosphorylation

up-regulates activity

0.444

PFK-2 that was phosphorylated on Ser466, but not Ser483, by PKA did not bind to 14-3-3s‚

SIGNOR-250025

P12931

P15941

1

phosphorylation

up-regulates

0.444

The c-src tyrosine kinase regulates signaling of the human df3/muc1 carcinoma-associated antigen with gsk3 beta and betBeta-catenin c-src phosphorylates the muc1 cytoplasmic domain at a yekv motif c-src-mediated phosphorylation of muc1 increases binding of muc1 and betBeta-catenin

SIGNOR-85938

Q99933

O75807

1

null

down-regulates activity

0.444

Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions.|BAG-1 negatively modulates GADD34-bound PP1 activity, and the expression of BAG-1 isoforms can also mask GADD34-mediated inhibition of colony formation and suppression of transcription. Our findings suggest that BAG-1 may function to suppress the GADD34-mediated cellular stress response and support a role for BAG-1 in the survival of cells undergoing stress.

SIGNOR-254117

P53350

Q6IBW4

1

phosphorylation

up-regulates activity

0.444

Plk1 phosphorylation of CAP-H2 at Ser288 is required for the accumulation of CAP-H2 and accurate chromosomal condensation during prophase.

SIGNOR-278419

P08311

P05546

1

cleavage

down-regulates activity

0.444

Amino acid sequence analysis led to the conclusion that both neutrophil elastase and cathepsin G cleave HC at Ile66, which does not affect HC activity, and at Val439, near the reactive site Leu444, which inactivates HC.

SIGNOR-256509

Q6N021

O15294

1

binding

up-regulates

0.444

Tet2 and tet3 associate with the o_glcnac transferase ogt / tet2 and tet3 promote ogt_mediated glcnacylation

SIGNOR-200695

P48546

P63092

1

binding

up-regulates activity

0.444

The GPCRs are allocated in five families where the GLP-1R and GIPR are found within the secretin family, also classified as class B [31,32]. Upon stimulation by an extracellular stimuli (ligand), GPCRs undergo conformational changes, and triggers downstream intracellular signals by coupling with G proteins (or other intracellular proteins such as arrestins), causing a wide range of both physiological and pathological processes.To stimulate insulin secretion, and in the presence of elevated blood glucose concentrations, GLP-1R activation in pancreatic beta cells promote recruitment and activation of Gαs protein leading to adenylate cyclase-mediated cAMP production, elevation of Ca2+, and ERK1/2 phosphorylation (Fig. 3)

SIGNOR-278138

P34969

P38405

1

binding

up-regulates activity

0.444

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-256926

P49757

Q00987

2

binding

down-regulates

0.444

Numb interacts with mdm2, and inhibits its ubiquitin-ligase function on tp53 (which in itself is inhibitory for tp53), thus numb activates (b) tp53

SIGNOR-168454

O95376

Q96P20

1

ubiquitination

up-regulates activity

0.444

ARIH2 can ubiquitinate NLRP3 via the NACHT domain of NLRP3, and the RING2 domain of ARIH2 is required for NLRP3 ubiquitination 65.|Overexpression of ARIH2 promotes NLRP3 ubiquitination and inhibits NLRP3 inflammasome activation 65.

SIGNOR-278686

P53779

Q93045

1

phosphorylation

down-regulates

0.444

We demonstrate that purified scg10 can be phosphorylated by two subclasses of mitogen-activated protein (map) kinases, c-jun n-terminal/stress-activated protein kinase (jnk/sapk) and p38 map kinase;jnk3/sapkbeta phosphorylation occurs at ser-62 and ser-73, residues that result in reduced microtubule-destabilizing activity for scg10.

SIGNOR-112114

P49841

P48436

1

phosphorylation

down-regulates activity

0.444

(E) The SOX9 K2 domain is phosphorylated by GSK3\u03b2 at T236.|Based on our findings that inhibition of GSK3\u03b2 prevents DNA damage-induced SOX9 degradation, and that FBW7 targets SOX9 for degradation after DNA damage, we reasoned that phosphorylation of SOX9 by GSK3\u03b2 is required for FBW7-mediated SOX9 degradation.

SIGNOR-279725

Q8IXJ9

P10276

1

binding

up-regulates activity

0.444

Therefore, ASXL1, a vertebrate PcG/TrxG protein, may mediate RA-regulated cell growth by modulating RAR activity.Finally, the ASXL1-induced accumulation of acetylated H3 may enhance the RAR-mediated transcriptional activity. In this study, we demonstrate that mammalian ASXL1 interacts with the AF-2 AD core of RAR (and RXR) through a novel, promiscuous NR box (LVMQLL) and enhances transcriptional activity of the receptors in certain cells.

SIGNOR-255910

O15297

Q13950

1

dephosphorylation

up-regulates activity

0.444

Activating dephosphorylation of RUNX2 by Wip1 increases its transcriptional activity on the Bax promoter.

SIGNOR-277110

P53350

Q00613

1

phosphorylation

down-regulates

0.444

Hsf1 was phosphorylated by plk1 at ser(216) of the dsgxxs motif during the timing of mitosis and a phospho-defective mutant form of hsf1 inhibited mitotic progression. Phosphorylated hsf1 during spindle pole localization underwent ubiquitin degradation through the scf(beta-trcp) pathway.

SIGNOR-180915

P62136

P27361

1

dephosphorylation

down-regulates

0.444

P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3). the dual specificity phosphatases that specifically dephosphorylate and inactivate the p-erk1/2 are called mapk phosphatases

SIGNOR-103155

Q9Y577

Q07820

1

polyubiquitination

down-regulates quantity by destabilization

0.444

Here, we identified Trim17 as a novel E3 ubiquitin-ligase for Mcl-1. Indeed, Trim17 co-immunoprecipitated with Mcl-1. Trim17 ubiquitinated Mcl-1 in vitro. Overexpression of Trim17 decreased the protein level of Mcl-1 in a phosphorylation- and proteasome-dependent manner. Finally, knock down of Trim17 expression reduced both ubiquitination and degradation of Mcl-1 in neurons.

SIGNOR-272032

O14559

P63000

1

gtpase-activating protein

down-regulates activity

0.444

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-260491

Q92630

O14746

1

phosphorylation

down-regulates activity

0.444

Dyrk2 phosphorylates TERT protein, a catalytic subunit of telomerase.|In this study, we found that dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 2 (Dyrk2) negatively regulates telomerase activity.

SIGNOR-279611

Q00526

P05412

1

phosphorylation

up-regulates

0.443

Egf-induced cdk3 activation caused c-jun phosphorylation at ser63 and ser73, resulting in increased ap-1 transactivation.

SIGNOR-183013

Q13315

O75150

1

phosphorylation

up-regulates

0.443

E3 ubiquitin ligase, a heterodimeric complex of the ringfinger rfn20/rfn40 is phosphorylated by atm.

SIGNOR-175003

P18031

Q16539

1

dephosphorylation

down-regulates activity

0.443

Here, we show that PTP1B regulates CD40 and BAFF-R signaling and dephosphorylates the mitogen-activated protein kinase p38.|Specifically, PTP1B counteracts p38 mitogen-activated protein kinase activation by directly dephosphorylating Tyr182 of this kinase.

SIGNOR-277167

Q8TF42

P22681

1

binding

down-regulates

0.443

Sts-1 and sts-2 contain sh3 domains that interacted with cbl, ub-associated domains, which bound directly to mono-ub or to the egfr/ub chimera as well as phosphoglycerate mutase domains that mediated oligomerization of sts-1/2. Ligand-induced recruitment of sts-1/sts-2 into activated egfr complexes led to inhibition of receptor internalization, reduction in the number of egfr-containing endocytic vesicles, and subsequent block of receptor degradation followed by prolonged activation of mitogenic signaling pathways.

SIGNOR-124897

P68400

Q04206

1

phosphorylation

up-regulates activity

0.443

We demonstrate that casein kinase II (CKII) interacts with p65 in vivo and can phosphorylate p65 at serine 529 in vitro. A CKII inhibitor (PD144795) inhibited TNFalpha-induced p65 phosphorylation in vivo. Furthermore, our results indicate that the association between IkappaBalpha and p65 inhibits p65 phosphorylation by CKII and that degradation of IkappaBalpha allows CKII to phosphorylate p65 to increase NF-kappaB transactivation potential.

SIGNOR-250942

Q00526

P06400

1

phosphorylation

down-regulates

0.443

The active form of prb is underphosphorylated. Cdk3/cyclin-c-mediated phosphorylation at ser-807 and ser-811 is required for g0-g1 transition.

SIGNOR-124212

P15976

P23769

1

transcriptional regulation

down-regulates quantity by repression

0.443

GATA-2 induces the expression of GATA-1, which first activates its cofactor FOG-1, and then downregulates GATA-2 cooperatively with FOG-1.

SIGNOR-256060

P04637

P35232

1

binding

up-regulates activity

0.443

Our previous studies have shown that prohibitin physically interacts with the marked-box domain of E2F family members and represses their transcriptional activity; in contrast, prohibitin could bind to and enhance the transcriptional activity of p53.

SIGNOR-268978

P14618

P40763

1

phosphorylation

up-regulates activity

0.443

PKM2 activates transcription of MEK5 by phosphorylating stat3 at Y705. In vitro phosphorylation assays show that PKM2 is a protein kinase using PEP as a phosphate donor

SIGNOR-267716

O15084

P36873

1

binding

up-regulates activity

0.443

Phosphatase Interactor Targeting K protein (PITK) was previously identified as a novel PP1 targeting subunit implicated in modulating the phosphorylation of the transcriptional regulator heterogeneous nuclear ribonucleoprotein K (hnRNP K)

SIGNOR-264794

Q6ZMQ8

Q15078

1

binding

up-regulates

0.443

Apoptosis-associated tyrosine kinase is a cdk5 activator p35 binding protein.

SIGNOR-118403

Q9UKB1

O14920

1

binding

down-regulates quantity by destabilization

0.443

We identified a human F-box/WD40 repeats protein (HOS), which is homologous to Slimb/h betaTrCP. Being a part of SCF complex with Skp1 and Cullin1, HOS specifically interacted with the phosphorylated IkappaB and beta-catenin, targeting these proteins for proteasome-dependent degradation in vivo.

SIGNOR-272544

Q00535

Q13224

1

phosphorylation

down-regulates quantity

0.443

Cdk5 phosphorylates NR2B at Ser1116 and controls surface level expression.|Reduction in Cdk5 activity, as well as disruption of Cdk5-NR2B interactions consistently increased NR2B surface levels and facilitated NMDA mediated synaptic function.

SIGNOR-278265

O43151

O15294

1

binding

up-regulates

0.443

Tet2 and tet3 associate with the o_glcnac transferase ogt / tet2 and tet3 promote ogt_mediated glcnacylation

SIGNOR-200729

P12931

Q13936

1

phosphorylation

up-regulates activity

0.443

Cotransfection of human embryonic kidney (HEK)-293 cells with hCa(v)1.2b and c-Src resulted in tyrosine phosphorylation of the calcium channel, which was prevented by nitration of tyrosine residues by peroxynitrite. Whole cell calcium currents were reduced by 58 + 5% by the Src kinase inhibitor PP2 and 64 + 6% by peroxynitrite.

SIGNOR-276081

P27361

P36956

1

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

P29323

Q13224

1

phosphorylation

up-regulates quantity

0.443

In addition, EPHB2 signaling leads to phosphorylation of GluN2B at tyrosine residue 1472 preventing clathrin dependent endocytosis, and increasing the surface retention of GluN2B containing NMDARs.

SIGNOR-279710

P54646

O60825

1

phosphorylation

up-regulates activity

0.443

AMPK phosphorylates and activates heart PFK-2 in vitro and in intact cells. activation of PFK-2 was due to the phosphorylation of Ser466

SIGNOR-250323

Q96Q27

P21333

1

polyubiquitination

down-regulates quantity by destabilization

0.442

ASB2 is the specificity subunit of an E3 ubiquitin ligase complex and is proposed to exert its effects by regulating the turnover of specific proteins; however, no ASB2 substrates had been identified. Here, we report that ASB2 targets the actin-binding proteins filamin A and B for proteasomal degradation.

SIGNOR-271740

P68400

P08575

1

phosphorylation

up-regulates

0.442

Mutational analysis of ck2 consensus sites showed that the target for ck2 was in an acidic insert of 19 amino acids in the d2 domain, and ser to ala mutations at amino acids 965, 968, 969, and 973 abrogated ck2 phosphorylation of cd45. Ck2 phosphorylation increased cd45 activity 3-fold toward phosphorylated myelin basic protein,

SIGNOR-65277

P06213

P60484

1

phosphorylation

down-regulates activity

0.442

Our results show that the kinase region of IRβ subunit physically binds to PTEN and phosphorylates on Y27 and Y174. In the current study, we discovered that IR also downregulates PTEN through tyrosine phosphorylation and suggest that Y27 and 174 are the two key tyrosines.

SIGNOR-276470

P62324

P17482

1

binding

up-regulates activity

0.442

The leukemia-associated protein Btg1 and the p53-regulated protein Btg2 interact with the homeoprotein Hoxb9 and enhance its transcriptional activation.

SIGNOR-221019

P17252

P19086

1

phosphorylation

up-regulates

0.442

Functional role of amino-terminal serine16 and serine27 of g alphaz in receptor and effector coupling.

SIGNOR-48681

Q96BR1

P49841

1

phosphorylation

down-regulates activity

0.442

Phosphorylation of GSK3 by PKB or SGK1 inhibits GSK3 activity|estern blotting using an antibody specific for the PKB/SGK1 consensus phosphorylation site in GSK3a/beta (serine 21 and 9 respectively) revealed an increase in GSK3a/beta phosphorylation in human embryonic kidney 293 (HEK293) cells overexpressing wild type SGK1, constitutively active SGK1, but not catalytically inactive SGK1.|The effect of SGK1 was mimicked by PKB and SGK3.

SIGNOR-249167

Q8IYK4

P02452

1

glycosylation

up-regulates activity

0.442

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

SIGNOR-261156

P05186

P10451

1

dephosphorylation

down-regulates activity

0.442

This result suggests that endogenous mouse TNAP dephosphorylates OPN in osteoblasts and that overexpressed human TNAP dephosphorylates OPN, compensating for the lack of endogenous TNAP in [Col1a1-Tnap +/\u2212 ;Alpl \u2212/\u2212 ] cells.

SIGNOR-277045

P68871

Q86VB7

1

binding

up-regulates activity

0.442

These data suggest that hemoglobin may mediate a stimulatory effect on erythropoiesis through the activation of CD163 on hematopoietic progenitor cells.

SIGNOR-251746

P04626

P49327

1

phosphorylation

up-regulates activity

0.442

Conversely, HER2 directly phosphorylates and activates FASN, while it also promotes FASN gene expression ( xref ; xref ).|Conversely, HER2 directly phosphorylates and activates FASN, while it also promotes FASN gene expression.

SIGNOR-278399

Q12923

P25963

1

dephosphorylation

up-regulates quantity by stabilization

0.442

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

SIGNOR-248712

O14965

Q9UPY8

1

phosphorylation

up-regulates

0.442

Aurora-a and aurora-b phosphorylate eb3 at ser-176 in a spatial and cell cycle-specific manner, respectively during mitosis two kinases, aurora-a and aurora-b, phosphorylate eb3 at ser-176, and the resulting phosphorylation disrupts the eb3-siah-1 complex. Indeed, eb3 is stabilized during mitosis and facilitates cell cycle progression.

SIGNOR-187657

P01148

P18146

1

binding

up-regulates activity

0.442

EGR1 bound to two binding sites on the LHB promoter and this binding was increased by GNRH1. Mutation of either site or knockdown of endogenous EGR1 decreased basal and/or GNRH1-regulated promoter activity.

SIGNOR-254918

P19419

P17252

1

transcriptional regulation

up-regulates quantity by expression

0.442

The luciferase reporter assay results revealed that the presence of both MZF-1 and Elk-1 significantly contributed to the upregulation of PKCα gene transcription activity.

SIGNOR-256336

O15013

P63000

1

guanine nucleotide exchange factor

up-regulates activity

0.442

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-260536

O95071

Q8IYW5

1

ubiquitination

down-regulates quantity

0.442

Here, we show that TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage. We find that RNF168 can be saturated by increasing amounts of DSBs. Depletion of TRIP12 and UBR5 allows accumulation of RNF168 to supraphysiological levels, followed by massive spreading of ubiquitin conjugates and hyperaccumulation of ubiquitin-regulated genome caretakers such as 53BP1 and BRCA1.

SIGNOR-266782

P54821

P11831

1

binding

up-regulates

0.442

The human homeodomain proteinphox1interacts functionally with serum response factor (srf) to impart serum responsive transcriptional activity to srf-binding sites in a hela cell cotransfection assay.

SIGNOR-52657

Q9Y6E0

Q9Y2H1

1

phosphorylation

up-regulates

0.441

Ndr1/ndr2 protein kinase is activated by phosphorylation on the activation loop phosphorylation site ser281/ser282 and the hydrophobic motif phosphorylation site thr444/thr442. Autophosphorylation of ndr is responsible for phosphorylation on ser281/ser282, whereas thr444/thr442 is targeted by an upstream kinase. Here we show that mst3, a mammalian ste20-like protein kinase, is able to phosphorylate ndr protein kinase at thr444/thr442. In vitro, mst3 selectively phosphorylated thr442 of ndr2, resulting in a 10-fold stimulation of ndr activity.

SIGNOR-142510

O00255

Q9BXW9

1

binding

up-regulates

0.441

Menin interacts with fancd2 / loss of menin expression in mouse embryonic fibroblasts leads to increased sensitivity to dna damage. Furthermore, menin is localized to chromatin and nuclear matrix, and the association with nuclear matrix is enhanced by gamma-irradiation. Together, these results suggest that menin plays a critical role in repair of dna damage in concert with fancd2.

SIGNOR-103947

Q14164

Q9NQC7

1

phosphorylation

down-regulates activity

0.441

CYLD is phosphorylated by IKK\u03b5 at Ser418.|Together, these observations demonstrate that I\u03baB kinase\u03b5-mediated phosphorylation of CYLD at Ser418 inhibits CYLD deubiquitinase activity.

SIGNOR-278311

P53350

P36956

1

phosphorylation

up-regulates activity

0.441

As illustrated in , the turnover of nuclear SREBP1a was attenuated in the presence of Plk1, confirming that Plk1 stabilizes nuclear SREBP1 by reducing its degradation.|Figure 2.Plk1 phosphorylates threonine 424, serine 467 and serine 486 in nuclear SREBP1 during mitosis. (A) In vitro kinase assay with recombinant nuclear SREBP1a and Plk1.

SIGNOR-279382

P28482

P07101

1

phosphorylation

up-regulates

0.441

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 hydroxylase in vitro at comparable rates to other proteins thought to be physiological substrates of these protein kinases.The effect on activity of phosphorylating both ser31 and ser40 was not additive. The possible roles of mapkap kinase-1, mapkap kinase-2 and map kinase in the regulation of tyrosine hydroxylase in vivo are discussed.

SIGNOR-34674

Q9UK97

Q9Y4R8

1

binding

down-regulates quantity by destabilization

0.441

Here we report that Tel2 and Tti1 are targeted for degradation within mTORC1 by the SCFFbxo9 ubiquitin ligase to adjust mTOR signalling to growth factor availability. The interaction between Tel2/Tti1 and Fbxo9 identified by mass spectrometry suggests that SCFFbxo9 is probably the ubiquitin ligase that mediates degradation of both proteins.

SIGNOR-271996

P38398

Q03468

1

polyubiquitination

down-regulates quantity by destabilization

0.441

BRCA1 polyubiquitinates CSB and this polyubiquitination and subsequent degradation of CSB occur following UV irradiation, even in the absence of Cockayne syndrome A (CSA) protein.

SIGNOR-272754

P60484

Q99801

1

dephosphorylation

up-regulates quantity by stabilization

0.441

Loss of PTEN Accelerates NKX3.1 Degradation to Promote Prostate Cancer Progression.|PTEN was also able to dephosphorylate NKX3.1 at threonine 179, a target of protein kinase C, but not threonine residues 89 and 93, targeted by casein kinase 2 .

SIGNOR-277026

Q9UKB1

O15111

1

binding

down-regulates quantity by destabilization

0.441

We identified a human F-box/WD40 repeats protein (HOS), which is homologous to Slimb/h betaTrCP. Being a part of SCF complex with Skp1 and Cullin1, HOS specifically interacted with the phosphorylated IkappaB and beta-catenin, targeting these proteins for proteasome-dependent degradation in vivo.

SIGNOR-272545

P05771

P14679

1

phosphorylation

up-regulates

0.441

We conclude that pkc-beta activates tyrosinase directly by phosphorylating serine residues at positions 505 and 509 in the cytoplasmic domain of this melanosome-associated protein. our results strongly suggest that direct phosphorylation of tyrosinase by pkc-_ leads to its activation.

SIGNOR-67870

O14519

P24941

1

binding

down-regulates activity

0.441

The ubiquitously expressed CDK2AP1 protein is the only known specific inhibitor of CDK2, making it an important component of cell cycle regulation during G1-to-S phase transition.

SIGNOR-264781

Q96EB6

O15105

1

deacetylation

down-regulates

0.441

Sirt1 reversed acetyl-transferase (p300)-mediated acetylation of two lysine residues (lys-64 and -70) on smad7. sirt1-mediated deacetylation of smad7 enhanced smad ubiquitination regulatory factor 1 (smurf1)-mediated ubiquitin proteasome degradation, which contributed to the low expression of smad7 in sirt1-overexpressing mesangial cells.

SIGNOR-150595

Q03164

P17947

1

methylation

up-regulates quantity by expression

0.441

Furthermore, we show that both MLL and AML1/CBFβ are required for maintaining the H3K4-me3 mark at the PU.1 upstream regulatory element (URE) and promoter region, and for full PU.1 gene expression.

SIGNOR-255874

P17252

Q15139

1

phosphorylation

up-regulates

0.441

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

SIGNOR-66666

Q9UNE7

P54253

1

ubiquitination

down-regulates quantity by destabilization

0.441

CHIP protects from the neurotoxicity of expanded and wild-type ataxin-1 and promotes their ubiquitination and degradation|Interestingly, CHIP also interacts with and ubiquitinates unexpanded ataxin-1

SIGNOR-278666

P19484

P11279

1

transcriptional regulation

up-regulates quantity by expression

0.441

Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants

SIGNOR-276555

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

P00519

P78352

1

phosphorylation

up-regulates activity

0.441

Moreover, c-Abl phosphorylates PSD-95 at tyrosine 533.|c-Abl modulates the synaptic contact number and PSD-95 clustering.

SIGNOR-278391

P60484

P23528

1

dephosphorylation

up-regulates activity

0.441

Unexpectedly, cofilin-1 activation by PGE 2 was mediated by the protein phosphatase activity of PTEN (phosphatase and tensin homolog deleted on chromosome 10), with which it directly associated.|Unexpectedly, cofilin-1 dephosphorylation and activation in our model was mediated by the protein phosphatase activity of PTEN.

SIGNOR-276980

O00253

Q01718

1

binding

down-regulates activity

0.441

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 α, β, and γ melanocyte–stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins

SIGNOR-268696

P00533

O00750

1

phosphorylation

up-regulates

0.44

The n-terminal region of pi3k-c2beta was found to selectively interact with the egf receptor in vitro, suggesting that it mediates the association of this pi3k with the receptor.

SIGNOR-77195

Q96CN5

Q5TZA2

1

binding

up-regulates activity

0.44

Here, we show that LRRC45 is a centrosome linker that localizes at the proximal ends of the centrioles and forms fiber-like structures between them. Depletion of LRRC45 results in centrosome splitting during interphase. LRRC45 interacts with C-Nap1 and rootletin

SIGNOR-273704

Q02156

P17302

1

phosphorylation

down-regulates activity

0.44

Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication.|These data strongly suggest that PKC directly phosphorylates Cx43 on S368 in vivo, which results in a change in single channel behavior that contributes to a decrease in intercellular communication.

SIGNOR-144465

Q9UM73

Q92529

1

phosphorylation

up-regulates

0.44

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

SIGNOR-91537

Q9BY84

Q9UQF2

1

binding

up-regulates

0.44

Here we report that jip-1 also binds the dual-specificity phosphatases mkp7 and m3/6 via a region independent of its jnk binding domain. when mkp7 is bound to jip-1 it reduces jnk activation leading to reduced phosphorylation of the jnk target c-jun

SIGNOR-97173

O00222

P63092

1

binding

up-regulates activity

0.44

MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.

SIGNOR-264081

P47901

P63092

1

binding

up-regulates activity

0.44

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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256791

P31749

O75030

1

phosphorylation

down-regulates quantity by destabilization

0.44

We found that AKT phosphorylates MITF at S510. Phosphorylated MITF S510 enhances its affinity to TP53 and promotes CDKN1A expression. Phosphorylation of MITF by AKT induces its degradation

SIGNOR-277281

O00253

Q01726

1

binding

down-regulates activity

0.44

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-268699

O43353

O14733

1

phosphorylation

up-regulates activity

0.44

Collectively, the results suggest that RIPK2 binds to and activates MKK7.|Radioactive in vitro kinase assay showed that RIPK2 can directly phosphorylate kinase-dead (K149A) MKK7 (Fig.\u00a0 xref ).

SIGNOR-280105

O15294

Q8NFU7

1

glycosylation

up-regulates activity

0.44

The DNA demethylation enzyme Tet1 interacts with Ogt and is O-GlcNAcylated. Tet1 protein stability is positively regulated by O-GlcNAcylation, and its repression function on targeting genes is dependent on Ogt.

SIGNOR-259184

P53701

P99999

1

chemical modification

up-regulates activity

0.44

Cytochrome c oxidase catalyzes the reduction of molecular oxygen to water, a process in which four electrons, four protons, and one molecule of oxygen are consumed. The reaction is coupled to the pumping of four additional protons across the membrane. According to the currently accepted concept, the pumping of all four protons occurs after the binding of oxygen to the reduced enzyme and is exclusively coupled to the last two electron transfer steps.

SIGNOR-280296

P53350

Q76N32

1

phosphorylation

down-regulates quantity by destabilization

0.44

We show that the intercentrosomal linker protein Cep68 is degraded in prometaphase through the SCF(βTrCP) (Skp1-Cul1-F-box protein) ubiquitin ligase complex. Cep68 degradation is initiated by PLK1 phosphorylation of Cep68 on Ser 332, allowing recognition by βTrCP.

SIGNOR-275621

Q00535

P56817

1

phosphorylation

up-regulates activity

0.44

BACE1 is phosphorylated by p25 and Cdk5 at Thr252.|Our finding that p25/Cdk5 stimulates BACE1 activity supports that p25/Cdk5 may represent a promising target for the development of drugs to treat Alzheimer's disease.

SIGNOR-278249