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
P20336	Q92696	0	lipidation	up-regulates activity	0.569	Prenylation (or geranylgeranylation) of Rab GTPases is catalysed by RGGT (Rab geranylgeranyl transferase) and requires REP (Rab escort protein). In the classical pathway, REP associates first with unprenylated Rab, which is then prenylated by RGGT. In the alternative pathway, REP associates first with RGGT; this complex then binds and prenylates Rab proteins. Rab GTPases need to be geranylgeranylated on either one or two cysteine residues in their Ctermini in order to localize to the correct intracellular membrane and be functional	SIGNOR-265574
Q92793	Q9NR30	1	acetylation	down-regulates activity	0.245	Significantly, the activity of DDX21 is regulated by acetylation. Acetylation by CBP inhibits DDX21 activity, while deacetylation by SIRT7 augments helicase activity and overcomes R-loop-mediated stalling of RNA polymerases.\|acetylation of K18, K137, and K600 impairs the helicase activity of DDX21.	SIGNOR-275904
Q8TD19	Q8TDX7	1	phosphorylation	up-regulates activity	0.715	Nercc1 catalyzes the phosphorylation of nek6 (ser206) and the equivalent site on nek7 (ser195), resulting in a 20-25-fold activation of nek6/7 kinase activity	SIGNOR-103030
Q99075	P78536	0	cleavage	up-regulates activity	0.591	ADAM17 is involved in the release and activation of several growth factors and cytokine receptor ligands. Among the growth factors activated by ADAM17 are TGF-alpha, amphiregulin, epiregulin and HB-EGF	SIGNOR-259844
P17612	Q9UD71	1	phosphorylation	up-regulates activity	0.504	DARPP-32 (dopamine and cyclic AMP-regulated phospho-protein, relative molecular mass 32,000) is converted into an inhibitor of protein phosphatase 1 when it is phosphorylated by protein kinase A (PKA) at threonine 34.‚	SIGNOR-250031
P52948	Q08211	2	binding	up-regulates activity	0.356	Here we report on the identification of the DExH/D-box helicase DHX9 as an intranuclear Nup98 binding partner. Various results, including in vitro assays, show that the FG/GLFG region of Nup98 binds to N- and C-terminal regions of DHX9 in an RNA facilitated manner. Importantly, binding of Nup98 stimulates the ATPase activity of DHX9, and a transcriptional reporter assay suggests Nup98 supports DHX9-stimulated transcription.	SIGNOR-260954
Q8TDZ2	P00519	0	phosphorylation	up-regulates activity	0.312	Biochemical assays revealed Abl phosphorylates Mical to directly amplify Mical Redox-mediated F-actin disassembly.\|We now find that the Abl non receptor protein tyrosine kinase and oncoprotein signaling pathway activates Mical to direct multiple cellular effects - including extending and shaping cellular processes, guiding axons, and orchestrating cancer cell invasion, colony formation, and survival.	SIGNOR-279674
P15173	Q12857	0	transcriptional regulation	up-regulates quantity by expression	0.2	NFIA binds to and activates the brown-fat-specific enhancers even before differentiation and later facilitates the binding of PPARgamma\|NFIA has at least three functions on the transcriptional regulation of brown fat [2]. First, NFIA activates adipogenesis per se, through activating the transcription of Pparg, which encodes PPARgamma. Second, NFIA also activates the brown-fat-specific gene expression (such as Ucp1 and Ppargc1a) independent of the degree of adipocyte differentiation, through facilitating the binding of PPARgamma to the brown-fat-specific enhancers. Third, NFIA represses myogenesis through suppression of myogenic transcription factors such as Myod1 as well as Myog,	SIGNOR-263983
Q13950	Q16539	0	phosphorylation	up-regulates activity	0.367	Mechanistic analysis revealed that the TAK1–MKK3/6–p38 MAPK axis phosphorylated Runx2, promoting its association with the coactivator CREB-binding protein (CBP), which was required to regulate osteoblast genetic programs. These findings reveal an in vivo function for p38β and establish that MAPK signaling is essential for bone formation in vivo.	SIGNOR-255777
Q01130	Q00987	1	transcriptional regulation	up-regulates quantity by expression	0.279	Using MDM2 P1 and P2 promoter-reporter systems, we screened clones regulating MDM2 transcriptions in a p53-independent manner by overexpression. Nine clones from the screening library showed enhanced MDM2 promoter activity and MDM2 expression in p53-deficient HCT116 cells. Among them, six clones, including NTRK2, GNA15, SFRS2, EIF5A, ELAVL1, and YWHAB mediated MAPK signaling for expressing MDM2.	SIGNOR-260076
P08123	Q8NBJ5	0	glycosylation	up-regulates activity	0.429	Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.	SIGNOR-261153
Q8N122	P42345	0	phosphorylation	up-regulates activity	0.989	The phosphorylation of raptor is stimulated by insulin and inhibited by rapamycin. Importantly, the site-directed mutation of raptor at one phosphorylation site, Ser(863), reduced mTORC1 activity both in vitro and in vivo.	SIGNOR-184959
P43403	P29353	1	phosphorylation	up-regulates	0.677	The syk-family kinases (syk and zap-70) were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site on shc1 (iso2).	SIGNOR-59659
P63000	P98171	0	gtpase-activating protein	down-regulates activity	0.479	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-260460
Q13469	P16298	0	dephosphorylation	up-regulates	0.614	Calcineurin dephosphorylates members of the nuclear factor of activated T cells (NFAT)2 transcription factor family, allowing NFAT to translocate to the nucleus where it cooperates with other transcription factors to induce transcription of target genes.	SIGNOR-233438
O14920	Q92934	1	phosphorylation	down-regulates	0.263	Ikk phosphorylates bad at serine-26 (ser26) and primes it for inactivation.	SIGNOR-192614
Q9BV47	P04637	1	dephosphorylation	down-regulates activity	0.366	Dual-specificity phosphatase 26 is a novel p53 phosphatase and inhibits p53 tumor suppressor functions in human neuroblastoma\|Inhibiting DUSP26 expression in the IMR-32 neuroblastoma cell line enhanced doxorubicin-induced p53 phosphorylation at Ser20 and Ser37, p21, Puma, Bax expression as well as apoptosis	SIGNOR-248765
O43561	Q9Y4K3	0	ubiquitination	up-regulates activity	0.345	Interestingly, this study has demonstrated that the membrane-proximal region of linker for activation of T cells preceding tyrosine-132 mediates its association with TRAF6, which promotes the ubiquitination of linker for activation of T cells and, in turn, the phosphorylation of tyrosine residues on linker for activation of T cells.\|Moreover, LAT was ubiquitinated at Lysine 88 by TRAF6 via K63 linked chain.	SIGNOR-278675
Q15910	Q13315	0	phosphorylation	down-regulates quantity	0.458	Enhancer of zeste homolog 2 (EZH2), a core catalytic component of polycomb repressive complex 2, is a new ATM kinase target, and ATM-mediated phosphorylation of EZH2 on Ser734 reduces protein stability.\|We verified that S734 is the predominant ATM site on EZH2 by performing ATM in vitro kinase assays using GST-EZH2 fusion proteins as substrates (Fig. 2b). The phosphorylation signal was nearly lost when the EZH2-S734A mutant was used as substrate	SIGNOR-279586
Q16539	Q13950	1	phosphorylation	up-regulates activity	0.367	Mechanistic analysis revealed that the TAK1–MKK3/6–p38 MAPK axis phosphorylated Runx2, promoting its association with the coactivator CREB-binding protein (CBP), which was required to regulate osteoblast genetic programs. These findings reveal an in vivo function for p38β and establish that MAPK signaling is essential for bone formation in vivo.	SIGNOR-255777
Q9UQD0	Q13557	0	phosphorylation	up-regulates activity	0.281	CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability\|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.	SIGNOR-275792
Q5VZV1	P55072	1	methylation	up-regulates activity	0.308	We reveal that METTL21C trimethylates p97 on the Lys315 residue and found that loss of this modification reduced p97 hexamer formation and ATPase activity in vivo.	SIGNOR-255918
Q9NRD5	Q01954	1	relocalization	up-regulates activity	0.307	we found that the PDZ domain-containing protein PICK1 (protein interacting with C kinase) interacts specifically with the C-termini of BNC1 and ASIC. Our studies showing association of recombinant PICK1 with ASIC and BNC1, and the presence of both PICK1 and ASIC in the synaptosomal fraction	SIGNOR-223414
Q8WXH5	Q93034	2	binding	up-regulates activity	0.493	SOCS7 promotes Dab1 polyubiquitylation and degradation. SOCS7-CRL5 complexes stimulate the ubiquitylation and turnover of Dab1. SOCS7, a CRL5 substrate adaptor protein, is also required for neocortical layering. SOCS7-CRL5 complexes stimulate the ubiquitylation and turnover of Dab1.	SIGNOR-272141
Q8N103	P63000	1	gtpase-activating protein	down-regulates activity	0.402	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-260524
P49137	P27815	1	phosphorylation	down-regulates activity	0.347	Phosphorylation of cAMP-specific PDE4A5 (phosphodiesterase-4A5) by MK2 (MAPKAPK2) attenuates its activation through protein kinase A phosphorylation. In the present study, we show that PDE4A5 is phosphorylated at Ser147, within the regulatory UCR1 (ultraconserved region 1) domain conserved among PDE4 long isoforms, by MK2 (MAPK-activated protein kinase 2, also called MAPKAPK2). Phosphorylation by MK2, although not altering PDE4A5 activity, markedly attenuates PDE4A5 activation through phosphorylation by protein kinase A. This modification confers the amplification of intracellular cAMP accumulation in response to adenylate cyclase activation by attenuating a major desensitization system to cAMP.	SIGNOR-263078
P27708	P23443	0	phosphorylation	up-regulates activity	0.372	CAD as a direct substrate of S6K1. mTORC1 signaling posttranslationally regulated this metabolic pathway via its downstream target ribosomal protein S6 kinase 1 (S6K1), which directly phosphorylates S1859 on CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase), the enzyme that catalyzes the first three steps of de novo pyrimidine synthesis. The direct regulation of CAD by S6K1 serves as a mechanism to increase the pool of nucleotides available for the RNA and DNA synthesis that accompanies cell growth.	SIGNOR-267443
Q92783	P40818	2	binding	up-regulates quantity	0.535	Stability of the UBPY binding partner STAM is dramatically compromised in UBPY knockdown cells.	SIGNOR-266904
P17612	Q14847	1	phosphorylation	down-regulates activity	0.306	Lasp-1 binds to non-muscle filamentous (F) actin in vitro in a phosphorylation-dependent manner. Phosphorylation of recombinant lasp-1 with recombinant PKA increased the Kd and decreased the Bmax for lasp-1 binding to F-actin. PKA-dependent phosphorylation sites in rabbit lasp-1 to S99 and S146	SIGNOR-250074
O15530	Q9HBY8	1	phosphorylation	up-regulates activity	0.596	SGK2 and SGK3 are activated in vitro by PDK1, albeit more slowly than SGK1, and their activation is accompanied by the phosphorylation of Thr(193) and Thr(253) respectively. The PDK1-catalysed phosphorylation and activation of SGK2 and SGK3, like SGK1, is greatly potentiated by mutating Ser(356) and Ser(419) respectively to Asp, these residues being equivalent to the C-terminal phosphorylation site of PKB.	SIGNOR-250277
O75581	Q9ULT6	0	ubiquitination	down-regulates quantity	0.656	Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6.	SIGNOR-260112
P30679	P34981	2	binding	up-regulates activity	0.487	Ga16 is phosphorylated in vivo by PMA and by TRH receptor stimulation	SIGNOR-278132
Q9NRD1	Q96HE7	2	binding	down-regulates quantity by destabilization	0.2	Ero1L is a ubiquitination substrate of FBXO6. FBXO6 mediates the degradation of Ero1L through a ubiquitylation-dependent pathway. Overexpression of FBXO6 increased the polyubiquitination and decreased the stability of Ero1L, whereas inhibition of FBXO6 prolonged the half-life of Ero1L. FBXO6 is the substrate recognition component of a Skp1-Cullin1-F-box protein (SCF) ubiquitin E3 ligase complex	SIGNOR-272326
P68400	P61244	1	phosphorylation	down-regulates	0.361	Here, we have mapped the nh2-terminal in vivo phosphorylation sites of max to ser2 and ser11[...]	SIGNOR-35772
P63104	P45983	0	phosphorylation	down-regulates	0.371	Jnk phosphorylated 14-3-3 at ser-184 and 14-3-3 at ser-186 both in vitro and in vivo, and such phosphorylation reduced the affinity of 14-3-3 proteins for bax	SIGNOR-124020
P13569	P11142	2	binding	down-regulates quantity	0.672	JB12 cooperates with cytosolic Hsc70 and the ubiquitin ligase RMA1 to target CFTR and CFTRΔF508 for degradation. JB12 drives Hsc70 to associate with CFTR and the RMA1 E3 complex	SIGNOR-271492
P11387	P78527	0	phosphorylation	down-regulates quantity by destabilization	0.448	Here, we show that the Ku70/Ku80 heterodimer binds with topoI, and that the DNA-dependent protein kinase (DNA-PKcs) phosphorylates topoI on serine 10 (topoI-pS10), which is subsequently ubiquitinated by BRCA1.	SIGNOR-277352
P17947	Q02556	2	binding	up-regulates activity	0.594	We found that tyrosine phosphorylated ICSBP activates CYBB and NCF2 transcription, during late myeloid differentiation, by interacting with PU.1, IRF1 and CBP.	SIGNOR-222880
Q9Y608	Q92997	2	binding	up-regulates	0.387	In particular, a previously unrecognized activator, lrrfip2 (leucine-rich repeat in flightless interaction protein 2), was found that interacts with dvl to increase the cellular levels of _-catenin and activate _-catenin/lef/tcf-dependent transcriptional activity	SIGNOR-133429
P52948	P78406	2	binding	up-regulates activity	0.882	Nup98 is a major interacting partner of Rae1 and known to beinvolved in mRNA export.	SIGNOR-260868
Q92974	P27361	0	phosphorylation	up-regulates	0.29	Activates rhoa and as a result regulates actin assembly.	SIGNOR-160420
P03372	P11511	1	transcriptional regulation	down-regulates quantity by repression	0.516	By binding to S1, ERalpha down-regulates the aromatase promoter activity.	SIGNOR-271683
Q15418	P25963	1	phosphorylation	up-regulates activity	0.386	Mitogen activated ribosomal S6 kinase (p90 rsk1) phosphorylates IkappaBalpha at S32, binds IkappaBalpha in vivo, and overexpression of dominant negative p90 rsk1 inhibits degradation of IkappaBalpha in response to TPA.	SIGNOR-279311
Q16821	Q15418	0	phosphorylation	up-regulates activity	0.43	The protein G(M), which targets protein phosphatase 1 (PP1) to the glycogen particles and sarcoplasmic reticulum (SR) of striated muscles, is known to be phosphorylated at Ser48 and Ser67 in vitro by adenosine 3',5' cyclic monophosphate-dependent protein kinase (PKA) and at Ser48 by MAP kinase-activated protein kinase-1 (MAPKAP-K1, also called p90 RSK). The phosphorylation of Ser48 increases the rate at which the glycogen-associated PP1.G(M) complex dephosphorylates (activates) glycogen synthase, but the phosphorylation of Ser67 has the opposite effect, suppressing the activity of PP1 toward glycogen-bound substrates.	SIGNOR-249036
P46527	Q04917	2	binding	down-regulates	0.502	14-3-3_, 14-3-3_, and 14-3-3_ (but not 14-3-3_ and 14-3-3_) could form a complex with p27kip1 / we discovered that akt-mediated p27kip1phosphorylation directly induces p27kip1binding to 14-3-3 and cytoplasmic localization through phosphorylating the newly identified thr198residue.	SIGNOR-109771
O95644	P11309	0	phosphorylation	up-regulates activity	0.643	Phosphorylation of NFATC1 at PIM1 target sites is essential for its ability to promote prostate cancer cell migration and invasion. Here we have identified ten PIM1 target sites in NFATC1 and found that prevention of their phosphorylation significantly decreases the transcriptional activity as well as the pro-migratory and pro-invasive effects of NFATC1 in prostate cancer cells.	SIGNOR-276775
O95786	Q8NG06	0	ubiquitination	up-regulates activity	0.2	Specifically, the ubiquitin E3 ligase TRIM25 ubiquitinates K172 in the CARD2 of RIG-I, which is essential for the efficient interaction of RIG-I with MAVS and thereby for antiviral signal transduction	SIGNOR-264582
P62140	P04637	1	dephosphorylation	down-regulates activity	0.286	Protein serine/threonine phosphatase-1 dephosphorylates p53 at Ser-15 and Ser-37 to modulate its transcriptional and apoptotic activities\|In addition, our results reveal that one of the molecular mechanisms by which PP-1 promotes cell survival is to dephosphorylate p53, and thus negatively regulate p53-dependent death pathway.	SIGNOR-248572
Q6ZMQ8	Q15078	2	binding	up-regulates	0.443	Apoptosis-associated tyrosine kinase is a cdk5 activator p35 binding protein.	SIGNOR-118403
Q96SD1	Q13315	0	phosphorylation	up-regulates	0.619	The artemis nuclease is defective in radiosensitive severe combined immunodeficiency patients and is required for the repair of a subset of ionising radiation induced dna double-strand breaks (dsbs) in an atm and dna-pk dependent process. Here, we show that artemis phosphorylation by atm and dna-pk in vitro is primarily attributable to s503, s516 and s645 and demonstrate atm dependent phosphorylation at serine 645 in vivo	SIGNOR-148315
O96006	P46783	1	transcriptional regulation	up-regulates quantity by expression	0.2	HDRE-like sequences act as positive regulatory elements for RP gene promoter activities in vivo. \| Cotransfection of a plasmid expressing hDREF increased luciferase expression directed by each RP gene promoter more than 30% compared with the values obtained without the hDREF-expressing plasmid.	SIGNOR-266083
Q9H6Z4	Q15418	0	phosphorylation	up-regulates quantity	0.319	RSK phosphorylates RanBP3 at Serine 58 residue in vitro and in vivo.RanBP3 phosphorylation increases its affinity towards Ran	SIGNOR-276149
Q12834	P24941	0	phosphorylation	down-regulates activity	0.684	Here we show that cyclin A2-Cdk2 binds and phosphorylates Cdc20 in interphase and this inhibits APC/C-Cdc20 activity.\|Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry.	SIGNOR-279322
Q13309	O00755	2	binding	down-regulates activity	0.2	These findings suggested that Wnt7a upregulated P21 and P27 by inactivating SKP2.	SIGNOR-278876
P63092	P08631	2	binding	up-regulates activity	0.2	Galphas and Galphai similarly modulate Hck, another member of Src-family tyrosine kinases.	SIGNOR-256529
P49757	Q6PML9	0	ubiquitination	down-regulates quantity by destabilization	0.2	Lnx functions as a ring type e3 ubiquitin ligase that targets the cell fate determinant numb for ubiquitin-dependent degradation.	SIGNOR-113704
P12694	O14874	0	phosphorylation	down-regulates	0.609	Phosphorylation sites and inactivation of branched-chain alpha-ketoacid dehydrogenase isolated from rat heart, bovine kidney, and rabbit liver, kidney, heart, brain, and skeletal muscle.	SIGNOR-25084
P20962	P04150	1	transcriptional regulation	up-regulates quantity by expression	0.328	Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner	SIGNOR-268460
Q9Y613	P12931	0	phosphorylation	up-regulates activity	0.306	Our results show that only Src can efficiently phosphorylate FHOD1 at Y99 to enable the downstream activation by ROCK.	SIGNOR-276612
Q05209	Q14289	1	dephosphorylation	down-regulates activity	0.544	Inhibition of the catalytic activity of cell adhesion kinase beta by protein-tyrosine phosphatase-pest-mediated dephosphorylation. / dephosphorylation of tyr402 and tyr579/580 by ptp-pest	SIGNOR-107502
P18031	Q14247	1	dephosphorylation	up-regulates activity	0.516	We conclude that Mena INV promotes invadopodium maturation by inhibiting normal dephosphorylation of cortactin at tyrosine 421 by the phosphatase PTP1B.	SIGNOR-277027
P05067	Q9NYY3	0	phosphorylation	up-regulates activity	0.348	Here we show that Polo-like kinase 2 (Plk2), an activity-inducible regulator of homeostatic plasticity, directly binds and phosphorylates threonine-668 and serine-675 of APP in\u00a0vitro and associates with APP in\u00a0vivo.\|Plk2 was necessary and sufficient to induce BACE-1-mediated APP amyloidogenic processing following overexcitation, associated intimately with APP, and directly phosphorylated the APP C-terminus.	SIGNOR-279424
P31751	P15336	1	phosphorylation	up-regulates activity	0.426	Taken together, these data suggest that AMPK regulates EC migration through phosphorylation of AKT2, which promotes ATF2 transactivation of MMP-2 during EC migration.\|Within this subgroup, we chose AKT2 for analysis because AKT2 phosphorylates activating transcription factor 2 (ATF2) [ xref , xref ].	SIGNOR-280178
P21796	Q07812	2	binding	up-regulates activity	0.584	The recombinant pro-apoptotic proteins Bax and Bak accelerate the opening of VDAC	SIGNOR-249613
Q03001	P10914	0	transcriptional regulation	down-regulates quantity by repression	0.2	Transient transfection studies with BPAG1 promoter-luciferase reporter gene plasmids and IRF1 and IRF2 expression plasmids revealed that IRF1 and IRF2 directly down-regulated BPAG1 gene transcription in cultured normal human epidermal keratinocytes.	SIGNOR-254492
P51587	Q9Y253	2	binding	up-regulates	0.553	Palb2 and brca2 interact with pol_ and are required to sustain the recruitment of pol_ at blocked replication forks. Palb2 and brca2 stimulate pol_-dependent dna synthesis on d loop substrates	SIGNOR-204538
P62993	P04626	0	relocalization	up-regulates	0.85	All erbb ligands and receptors couple to activation of the ras-mapk pathway, either directly through sh2 domain-mediated recruitment of grb-2 or indirectly through ptb domain-mediated binding of the shc adaptor	SIGNOR-121968
P52907	Q6JBY9	2	binding	up-regulates	0.667	An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B). Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.	SIGNOR-263088
Q96SB3	Q13009	2	binding	up-regulates quantity	0.422	Spinophilin binding promotes the plasma membrane localization of Tiam1 and enhances the ability of Tiam1 to activate p70 S6 kinase.	SIGNOR-269175
P0DP24	Q8N5S9	2	binding	up-regulates	0.488	The binding of Ca2+/CaM to CaM-KK is absolutely required for its activation and efficient phosphorylation of target protein kinases	SIGNOR-266328
P00519	Q7Z434	1	phosphorylation	up-regulates activity	0.453	A phosphotyrosine specific antibody indicated that MAVS was phosphorylated by c-Abl.	SIGNOR-279673
P29474	P31749	0	phosphorylation	up-regulates	0.877	Recently many investigators have shown that protein phosphorylation of enos by several serine/threonine kinases is a critical control step for no production by endothelial cells. Phosphorylation by amp kinase, akt (or protein kinase b), or protein kinase a on serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no.	SIGNOR-112363
P06400	Q00526	0	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
P30305	P68400	0	phosphorylation	up-regulates activity	0.338	Mass spectrometry analysis demonstrates that at least two serine residues, Ser-186 and Ser-187, are phosphorylated in vivo. \| Finally, we demonstrate that phosphorylation of CDC25B by protein kinase CK2 increases the catalytic activity of the phosphatase in vitro as well as in vivo.	SIGNOR-250836
P31751	O60346	0	dephosphorylation	down-regulates activity	0.621	The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.\|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells.	SIGNOR-248328
Q8N2M8	P00519	0	phosphorylation	up-regulates activity	0.2	In biochemical assays and in Xenopus growth cones we find that Abl kinase activity enhances the association or co-localization of CLASP2 and F-actin, consistent with previous reports of CLASP binding to actin [Tsvetkov et al., ].\|In vitro, Abl phosphorylates CLASP with a Km of 1.89 \u00b5M, indicating that CLASP is a bona fide substrate.	SIGNOR-280166
P24941	O94986	0	relocalization	up-regulates activity	0.278	Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome.	SIGNOR-271724
P31644	Q8TAB3	2	binding	up-regulates quantity by stabilization	0.258	Here, we found that PCDH19 binds the alpha subunits of GABAAR and regulates its surface availability and currents in cultured hippocampal neurons. The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated. Here, we identified a new interaction between PCDH19 and GABAA receptor (GABAAR) alpha subunits in the rat brain. PCDH19 shRNA-mediated downregulation reduces GABAAR surface expression and affects the frequency and kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in cultured hippocampal neurons.	SIGNOR-267219
P15531	P15531	2	phosphorylation	up-regulates activity	0.2	An acid-stable (nonhistidine) phosphorylation was identified on autophosphorylated purified recombinant Nm23 proteins and [32P]orthophosphate-labeled human breast carcinoma and murine melanoma Nm23. Phosphoamino acid analysis identified serine as the acid-stable phosphorylation and serine 44 as the major site of phosphorylation. The biological relevance of the novel phosphorylation identified herein is suggested by the direct correlation of in vivo Nm23 acid-stable phosphorylation levels, but not Nm23 NDPK activity, with suppression of tumor metastatic potential among control and nm23-1 transfected murine melanoma cells.	SIGNOR-250303
Q9H3D4	Q6ZMZ3	1	transcriptional regulation	up-regulates quantity by expression	0.2	Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by a marked decrease in expression of several nuclear envelope-associated components (Lamin B1, Lamin A/C, Sun1, Nesprin-3, Plectin) compared with controls. Furthermore, chromatin immunoprecipitation-quantitative PCR assay showed enrichment of p63 on Sun1, Syne3, and Plec promoters, suggesting them as p63 targets.	SIGNOR-263280
O43318	P67775	0	dephosphorylation	down-regulates	0.329	Our results demonstrate that pp6 specifically down-regulates tak1 through dephosphorylation of thr-187 in the activation loop, which is likely important for suppressing inflammatory responses via tak1 signaling pathways.	SIGNOR-150369
P19086	P41145	2	binding	up-regulates activity	0.313	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-257105
Q99708	P38398	2	relocalization	up-regulates activity	0.842	DNA damage activates ATM and CHK2 kinases, which mediate phosphorylation of CtIP and BRCA1. Phosphorylated CtIP associates with BRCA1 and with the MRN complex leading to the recruitment of the BRCC complex at the site of DNA damage where HR is initiated.	SIGNOR-263203
P50148	Q5NUL3	2	binding	up-regulates activity	0.449	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-257371
P42345	P30622	1	phosphorylation	up-regulates activity	0.567	By contrast to the phosphorylation of p150 Glued by PKA, inhibition of mTOR by rapamycin inhibited the ability of CLIP-170 to bind to microtubules, suggesting that phosphorylation by mTOR promotes CLIP-170 microtubule binding.\|The new study confirms this physical interaction in animal cells and suggests that mTOR phosphorylates CLIP-170 on some, but not all, of the sites that are phosphorylated in vivo.	SIGNOR-279231
O43791	Q9Y6Q9	2	binding	down-regulates quantity by destabilization	0.479	Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations.	SIGNOR-272827
P31751	Q15365	1	phosphorylation	down-regulates activity	0.429	We show that heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) binds a structural, 33-nucleotide TGF-beta-activated translation (BAT) element in the 3' untranslated region of disabled-2 (Dab2) and interleukin-like EMT inducer (ILEI) transcripts, and represses their translation.TGF-beta activation leads to phosphorylation at Ser 43 of hnRNP E1 by protein kinase Bbeta/Akt2, inducing its release from the BAT element and translational activation of Dab2 and ILEI messenger RNAs.	SIGNOR-262625
Q99759	O43379	2	binding	up-regulates quantity by stabilization	0.2	Specifically, we demonstrate that MEKK3 interacts with WDR62 to stabilize WDR62 and regulates JNK activity in a synergic way. On the other hand, JNK activity also regulates the phosphorylation of WDR62 at T1053 in a feedback loop which facilities the recruitment of FBW7 degradation of WDR62	SIGNOR-271714
P60510	P53350	1	dephosphorylation	down-regulates activity	0.416	PPP4C dephosphorylated PLK1 at the S137 site, negatively regulating its activity in the DSB response in early embryonic cells.	SIGNOR-277076
P00519	Q96MU7	1	phosphorylation	down-regulates	0.305	We show that yt521-b is tyrosine phosphorylated by c-abl in the nucleus.We propose that tyrosine phosphorylation causes sequestration of YT521-B in an insoluble nuclear form, which abolishes the ability of YT521-B to change alternative splice sites.	SIGNOR-125167
P13861	P13861	2	phosphorylation	up-regulates activity	0.2	RII subunit containing the 'autophosphorylation' site (Ser-95)	SIGNOR-250073
Q16512	Q92974	1	phosphorylation	down-regulates	0.291	Here we identify a region in the carboxyl terminus of gef-h1 that is important for suppression of its guanine nucleotide exchange activity by microtubules. This portion of the protein includes a coiled-coil motif, a proline-rich motif that may interact with src homology 3 domain-containing proteins, and a potential binding site for 14-3-3 proteins. We show that phosphorylation of gef-h1 at ser(885) by pak1 induces 14-3-3 binding to the exchange factor and relocation of 14-3-3 to microtubules.	SIGNOR-122191
P51955	Q68D86	1	phosphorylation	down-regulates activity	0.2	CCDC102B is recruited to the centrosome by C-Nap1 (also known as CEP250) and interacts with the centrosome linker components rootletin and LRRC45. CCDC102B decorates and facilitates the formation of rootletin filaments. Furthermore, CCDC102B is phosphorylated by Nek2A (an isoform encoded by NEK2) and is disassociated from the centrosome at the onset of mitosis.	SIGNOR-275626
P30968	P50148	2	binding	up-regulates activity	0.474	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-257265
P00533	P46108	1	phosphorylation	down-regulates activity	0.74	To address these questions, we have developed an antibody that specifically recognizes the CrkII protein phosphorylated on Tyr221, and we found that the EGF receptor directly phosphorylates CrkII on Tyr221. Furthermore, we observed that the phosphorylation of Tyr221 of CrkII correlated with its dissociation from the EGF receptor, implicating the phosphorylation of Tyr221 in the negative feedback of binding to the EGF receptor.	SIGNOR-251091
Q4VCS5	O95835	0	phosphorylation	up-regulates quantity by stabilization	0.523	Here low serum and high LATS1 activity are found to enhance the levels of the 130-kDa isoform of angiomotin (Amot130) through phosphorylation by LATS1/2 at serine 175, which then forms a binding site for 14-3-3. Such phosphorylation, in turn, enables the ubiquitin ligase atrophin-1 interacting protein (AIP)4 to bind, ubiquitinate, and stabilize Amot130	SIGNOR-275843
Q9Y6K9	O43318	2	binding	up-regulates activity	0.815	This result suggests that ikkgamma/nemo binds to the polyubiquitinated tak1.	SIGNOR-162634
Q96J02	O15350	1	ubiquitination	down-regulates quantity by destabilization	0.566	Collectively, our present findings suggest that MDM2 promotes Itch-mediated degradation of p73 through the interaction with Itch in HeLa cells	SIGNOR-278699
Q9HBW0	P63096	2	binding	up-regulates	0.625	Lysophosphatidic acid (lpa), a major g protein coupled receptor (gpcr)-activating ligand present in serum, elicits growth factor like responses by stimulating specific gpcrs coupled to heterotrimeric g proteins such as g(i), g(q), and g12/13. lpa2 also can couple to the gi/o, g12/13, and gqfamilies.	SIGNOR-84559
P51955	Q99501	1	phosphorylation	up-regulates activity	0.2	Nek2A mediates G2/M phosphorylation of GAS2L1. GAS2L1 and its Ser352 phosphorylation are required for proper spindle organization and chromosome segregation.	SIGNOR-273683

P20336

Q92696

0

lipidation

up-regulates activity

0.569

Prenylation (or geranylgeranylation) of Rab GTPases is catalysed by RGGT (Rab geranylgeranyl transferase) and requires REP (Rab escort protein). In the classical pathway, REP associates first with unprenylated Rab, which is then prenylated by RGGT. In the alternative pathway, REP associates first with RGGT; this complex then binds and prenylates Rab proteins. Rab GTPases need to be geranylgeranylated on either one or two cysteine residues in their Ctermini in order to localize to the correct intracellular membrane and be functional

SIGNOR-265574

Q92793

Q9NR30

1

acetylation

down-regulates activity

0.245

Significantly, the activity of DDX21 is regulated by acetylation. Acetylation by CBP inhibits DDX21 activity, while deacetylation by SIRT7 augments helicase activity and overcomes R-loop-mediated stalling of RNA polymerases.|acetylation of K18, K137, and K600 impairs the helicase activity of DDX21.

SIGNOR-275904

Q8TD19

Q8TDX7

1

phosphorylation

up-regulates activity

0.715

Nercc1 catalyzes the phosphorylation of nek6 (ser206) and the equivalent site on nek7 (ser195), resulting in a 20-25-fold activation of nek6/7 kinase activity

SIGNOR-103030

Q99075

P78536

0

cleavage

up-regulates activity

0.591

ADAM17 is involved in the release and activation of several growth factors and cytokine receptor ligands. Among the growth factors activated by ADAM17 are TGF-alpha, amphiregulin, epiregulin and HB-EGF

SIGNOR-259844

P17612

Q9UD71

1

phosphorylation

up-regulates activity

0.504

DARPP-32 (dopamine and cyclic AMP-regulated phospho-protein, relative molecular mass 32,000) is converted into an inhibitor of protein phosphatase 1 when it is phosphorylated by protein kinase A (PKA) at threonine 34.‚

SIGNOR-250031

P52948

Q08211

2

binding

up-regulates activity

0.356

Here we report on the identification of the DExH/D-box helicase DHX9 as an intranuclear Nup98 binding partner. Various results, including in vitro assays, show that the FG/GLFG region of Nup98 binds to N- and C-terminal regions of DHX9 in an RNA facilitated manner. Importantly, binding of Nup98 stimulates the ATPase activity of DHX9, and a transcriptional reporter assay suggests Nup98 supports DHX9-stimulated transcription.

SIGNOR-260954

Q8TDZ2

P00519

0

phosphorylation

up-regulates activity

0.312

Biochemical assays revealed Abl phosphorylates Mical to directly amplify Mical Redox-mediated F-actin disassembly.|We now find that the Abl non receptor protein tyrosine kinase and oncoprotein signaling pathway activates Mical to direct multiple cellular effects - including extending and shaping cellular processes, guiding axons, and orchestrating cancer cell invasion, colony formation, and survival.

SIGNOR-279674

P15173

Q12857

0

transcriptional regulation

up-regulates quantity by expression

0.2

NFIA binds to and activates the brown-fat-specific enhancers even before differentiation and later facilitates the binding of PPARgamma|NFIA has at least three functions on the transcriptional regulation of brown fat [2]. First, NFIA activates adipogenesis per se, through activating the transcription of Pparg, which encodes PPARgamma. Second, NFIA also activates the brown-fat-specific gene expression (such as Ucp1 and Ppargc1a) independent of the degree of adipocyte differentiation, through facilitating the binding of PPARgamma to the brown-fat-specific enhancers. Third, NFIA represses myogenesis through suppression of myogenic transcription factors such as Myod1 as well as Myog,

SIGNOR-263983

Q13950

Q16539

0

phosphorylation

up-regulates activity

0.367

Mechanistic analysis revealed that the TAK1–MKK3/6–p38 MAPK axis phosphorylated Runx2, promoting its association with the coactivator CREB-binding protein (CBP), which was required to regulate osteoblast genetic programs. These findings reveal an in vivo function for p38β and establish that MAPK signaling is essential for bone formation in vivo.

SIGNOR-255777

Q01130

Q00987

1

transcriptional regulation

up-regulates quantity by expression

0.279

Using MDM2 P1 and P2 promoter-reporter systems, we screened clones regulating MDM2 transcriptions in a p53-independent manner by overexpression. Nine clones from the screening library showed enhanced MDM2 promoter activity and MDM2 expression in p53-deficient HCT116 cells. Among them, six clones, including NTRK2, GNA15, SFRS2, EIF5A, ELAVL1, and YWHAB mediated MAPK signaling for expressing MDM2.

SIGNOR-260076

P08123

Q8NBJ5

0

glycosylation

up-regulates activity

0.429

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

SIGNOR-261153

Q8N122

P42345

0

phosphorylation

up-regulates activity

0.989

The phosphorylation of raptor is stimulated by insulin and inhibited by rapamycin. Importantly, the site-directed mutation of raptor at one phosphorylation site, Ser(863), reduced mTORC1 activity both in vitro and in vivo.

SIGNOR-184959

P43403

P29353

1

phosphorylation

up-regulates

0.677

The syk-family kinases (syk and zap-70) were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site on shc1 (iso2).

SIGNOR-59659

P63000

P98171

0

gtpase-activating protein

down-regulates activity

0.479

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-260460

Q13469

P16298

0

dephosphorylation

up-regulates

0.614

Calcineurin dephosphorylates members of the nuclear factor of activated T cells (NFAT)2 transcription factor family, allowing NFAT to translocate to the nucleus where it cooperates with other transcription factors to induce transcription of target genes.

SIGNOR-233438

O14920

Q92934

1

phosphorylation

down-regulates

0.263

Ikk phosphorylates bad at serine-26 (ser26) and primes it for inactivation.

SIGNOR-192614

Q9BV47

P04637

1

dephosphorylation

down-regulates activity

0.366

Dual-specificity phosphatase 26 is a novel p53 phosphatase and inhibits p53 tumor suppressor functions in human neuroblastoma|Inhibiting DUSP26 expression in the IMR-32 neuroblastoma cell line enhanced doxorubicin-induced p53 phosphorylation at Ser20 and Ser37, p21, Puma, Bax expression as well as apoptosis

SIGNOR-248765

O43561

Q9Y4K3

0

ubiquitination

up-regulates activity

0.345

Interestingly, this study has demonstrated that the membrane-proximal region of linker for activation of T cells preceding tyrosine-132 mediates its association with TRAF6, which promotes the ubiquitination of linker for activation of T cells and, in turn, the phosphorylation of tyrosine residues on linker for activation of T cells.|Moreover, LAT was ubiquitinated at Lysine 88 by TRAF6 via K63 linked chain.

SIGNOR-278675

Q15910

Q13315

0

phosphorylation

down-regulates quantity

0.458

Enhancer of zeste homolog 2 (EZH2), a core catalytic component of polycomb repressive complex 2, is a new ATM kinase target, and ATM-mediated phosphorylation of EZH2 on Ser734 reduces protein stability.|We verified that S734 is the predominant ATM site on EZH2 by performing ATM in vitro kinase assays using GST-EZH2 fusion proteins as substrates (Fig. 2b). The phosphorylation signal was nearly lost when the EZH2-S734A mutant was used as substrate

SIGNOR-279586

Q16539

Q13950

1

phosphorylation

up-regulates activity

0.367

Mechanistic analysis revealed that the TAK1–MKK3/6–p38 MAPK axis phosphorylated Runx2, promoting its association with the coactivator CREB-binding protein (CBP), which was required to regulate osteoblast genetic programs. These findings reveal an in vivo function for p38β and establish that MAPK signaling is essential for bone formation in vivo.

SIGNOR-255777

Q9UQD0

Q13557

0

phosphorylation

up-regulates activity

0.281

CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.

SIGNOR-275792

Q5VZV1

P55072

1

methylation

up-regulates activity

0.308

We reveal that METTL21C trimethylates p97 on the Lys315 residue and found that loss of this modification reduced p97 hexamer formation and ATPase activity in vivo.

SIGNOR-255918

Q9NRD5

Q01954

1

relocalization

up-regulates activity

0.307

we found that the PDZ domain-containing protein PICK1 (protein interacting with C kinase) interacts specifically with the C-termini of BNC1 and ASIC. Our studies showing association of recombinant PICK1 with ASIC and BNC1, and the presence of both PICK1 and ASIC in the synaptosomal fraction

SIGNOR-223414

Q8WXH5

Q93034

2

binding

up-regulates activity

0.493

SOCS7 promotes Dab1 polyubiquitylation and degradation. SOCS7-CRL5 complexes stimulate the ubiquitylation and turnover of Dab1. SOCS7, a CRL5 substrate adaptor protein, is also required for neocortical layering. SOCS7-CRL5 complexes stimulate the ubiquitylation and turnover of Dab1.

SIGNOR-272141

Q8N103

P63000

1

gtpase-activating protein

down-regulates activity

0.402

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-260524

P49137

P27815

1

phosphorylation

down-regulates activity

0.347

Phosphorylation of cAMP-specific PDE4A5 (phosphodiesterase-4A5) by MK2 (MAPKAPK2) attenuates its activation through protein kinase A phosphorylation. In the present study, we show that PDE4A5 is phosphorylated at Ser147, within the regulatory UCR1 (ultraconserved region 1) domain conserved among PDE4 long isoforms, by MK2 (MAPK-activated protein kinase 2, also called MAPKAPK2). Phosphorylation by MK2, although not altering PDE4A5 activity, markedly attenuates PDE4A5 activation through phosphorylation by protein kinase A. This modification confers the amplification of intracellular cAMP accumulation in response to adenylate cyclase activation by attenuating a major desensitization system to cAMP.

SIGNOR-263078

P27708

P23443

0

phosphorylation

up-regulates activity

0.372

CAD as a direct substrate of S6K1. mTORC1 signaling posttranslationally regulated this metabolic pathway via its downstream target ribosomal protein S6 kinase 1 (S6K1), which directly phosphorylates S1859 on CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase), the enzyme that catalyzes the first three steps of de novo pyrimidine synthesis. The direct regulation of CAD by S6K1 serves as a mechanism to increase the pool of nucleotides available for the RNA and DNA synthesis that accompanies cell growth.

SIGNOR-267443

Q92783

P40818

2

binding

up-regulates quantity

0.535

Stability of the UBPY binding partner STAM is dramatically compromised in UBPY knockdown cells.

SIGNOR-266904

P17612

Q14847

1

phosphorylation

down-regulates activity

0.306

Lasp-1 binds to non-muscle filamentous (F) actin in vitro in a phosphorylation-dependent manner. Phosphorylation of recombinant lasp-1 with recombinant PKA increased the Kd and decreased the Bmax for lasp-1 binding to F-actin. PKA-dependent phosphorylation sites in rabbit lasp-1 to S99 and S146

SIGNOR-250074

O15530

Q9HBY8

1

phosphorylation

up-regulates activity

0.596

SGK2 and SGK3 are activated in vitro by PDK1, albeit more slowly than SGK1, and their activation is accompanied by the phosphorylation of Thr(193) and Thr(253) respectively. The PDK1-catalysed phosphorylation and activation of SGK2 and SGK3, like SGK1, is greatly potentiated by mutating Ser(356) and Ser(419) respectively to Asp, these residues being equivalent to the C-terminal phosphorylation site of PKB.

SIGNOR-250277

O75581

Q9ULT6

0

ubiquitination

down-regulates quantity

0.656

Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6.

SIGNOR-260112

P30679

P34981

2

binding

up-regulates activity

0.487

Ga16 is phosphorylated in vivo by PMA and by TRH receptor stimulation

SIGNOR-278132

Q9NRD1

Q96HE7

2

binding

down-regulates quantity by destabilization

0.2

Ero1L is a ubiquitination substrate of FBXO6. FBXO6 mediates the degradation of Ero1L through a ubiquitylation-dependent pathway. Overexpression of FBXO6 increased the polyubiquitination and decreased the stability of Ero1L, whereas inhibition of FBXO6 prolonged the half-life of Ero1L. FBXO6 is the substrate recognition component of a Skp1-Cullin1-F-box protein (SCF) ubiquitin E3 ligase complex

SIGNOR-272326

P68400

P61244

1

phosphorylation

down-regulates

0.361

Here, we have mapped the nh2-terminal in vivo phosphorylation sites of max to ser2 and ser11[...]

SIGNOR-35772

P63104

P45983

0

phosphorylation

down-regulates

0.371

Jnk phosphorylated 14-3-3 at ser-184 and 14-3-3 at ser-186 both in vitro and in vivo, and such phosphorylation reduced the affinity of 14-3-3 proteins for bax

SIGNOR-124020

P13569

P11142

2

binding

down-regulates quantity

0.672

JB12 cooperates with cytosolic Hsc70 and the ubiquitin ligase RMA1 to target CFTR and CFTRΔF508 for degradation. JB12 drives Hsc70 to associate with CFTR and the RMA1 E3 complex

SIGNOR-271492

P11387

P78527

0

phosphorylation

down-regulates quantity by destabilization

0.448

Here, we show that the Ku70/Ku80 heterodimer binds with topoI, and that the DNA-dependent protein kinase (DNA-PKcs) phosphorylates topoI on serine 10 (topoI-pS10), which is subsequently ubiquitinated by BRCA1.

SIGNOR-277352

P17947

Q02556

2

binding

up-regulates activity

0.594

We found that tyrosine phosphorylated ICSBP activates CYBB and NCF2 transcription, during late myeloid differentiation, by interacting with PU.1, IRF1 and CBP.

SIGNOR-222880

Q9Y608

Q92997

2

binding

up-regulates

0.387

In particular, a previously unrecognized activator, lrrfip2 (leucine-rich repeat in flightless interaction protein 2), was found that interacts with dvl to increase the cellular levels of _-catenin and activate _-catenin/lef/tcf-dependent transcriptional activity

SIGNOR-133429

P52948

P78406

2

binding

up-regulates activity

0.882

Nup98 is a major interacting partner of Rae1 and known to beinvolved in mRNA export.

SIGNOR-260868

Q92974

P27361

0

phosphorylation

up-regulates

0.29

Activates rhoa and as a result regulates actin assembly.

SIGNOR-160420

P03372

P11511

1

transcriptional regulation

down-regulates quantity by repression

0.516

By binding to S1, ERalpha down-regulates the aromatase promoter activity.

SIGNOR-271683

Q15418

P25963

1

phosphorylation

up-regulates activity

0.386

Mitogen activated ribosomal S6 kinase (p90 rsk1) phosphorylates IkappaBalpha at S32, binds IkappaBalpha in vivo, and overexpression of dominant negative p90 rsk1 inhibits degradation of IkappaBalpha in response to TPA.

SIGNOR-279311

Q16821

Q15418

0

phosphorylation

up-regulates activity

0.43

The protein G(M), which targets protein phosphatase 1 (PP1) to the glycogen particles and sarcoplasmic reticulum (SR) of striated muscles, is known to be phosphorylated at Ser48 and Ser67 in vitro by adenosine 3',5' cyclic monophosphate-dependent protein kinase (PKA) and at Ser48 by MAP kinase-activated protein kinase-1 (MAPKAP-K1, also called p90 RSK). The phosphorylation of Ser48 increases the rate at which the glycogen-associated PP1.G(M) complex dephosphorylates (activates) glycogen synthase, but the phosphorylation of Ser67 has the opposite effect, suppressing the activity of PP1 toward glycogen-bound substrates.

SIGNOR-249036

P46527

Q04917

2

binding

down-regulates

0.502

14-3-3_, 14-3-3_, and 14-3-3_ (but not 14-3-3_ and 14-3-3_) could form a complex with p27kip1 / we discovered that akt-mediated p27kip1phosphorylation directly induces p27kip1binding to 14-3-3 and cytoplasmic localization through phosphorylating the newly identified thr198residue.

SIGNOR-109771

O95644

P11309

0

phosphorylation

up-regulates activity

0.643

Phosphorylation of NFATC1 at PIM1 target sites is essential for its ability to promote prostate cancer cell migration and invasion. Here we have identified ten PIM1 target sites in NFATC1 and found that prevention of their phosphorylation significantly decreases the transcriptional activity as well as the pro-migratory and pro-invasive effects of NFATC1 in prostate cancer cells.

SIGNOR-276775

O95786

Q8NG06

0

ubiquitination

up-regulates activity

0.2

Specifically, the ubiquitin E3 ligase TRIM25 ubiquitinates K172 in the CARD2 of RIG-I, which is essential for the efficient interaction of RIG-I with MAVS and thereby for antiviral signal transduction

SIGNOR-264582

P62140

P04637

1

dephosphorylation

down-regulates activity

0.286

Protein serine/threonine phosphatase-1 dephosphorylates p53 at Ser-15 and Ser-37 to modulate its transcriptional and apoptotic activities|In addition, our results reveal that one of the molecular mechanisms by which PP-1 promotes cell survival is to dephosphorylate p53, and thus negatively regulate p53-dependent death pathway.

SIGNOR-248572

Q6ZMQ8

Q15078

2

binding

up-regulates

0.443

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

SIGNOR-118403

Q96SD1

Q13315

0

phosphorylation

up-regulates

0.619

The artemis nuclease is defective in radiosensitive severe combined immunodeficiency patients and is required for the repair of a subset of ionising radiation induced dna double-strand breaks (dsbs) in an atm and dna-pk dependent process. Here, we show that artemis phosphorylation by atm and dna-pk in vitro is primarily attributable to s503, s516 and s645 and demonstrate atm dependent phosphorylation at serine 645 in vivo

SIGNOR-148315

O96006

P46783

1

transcriptional regulation

up-regulates quantity by expression

0.2

HDRE-like sequences act as positive regulatory elements for RP gene promoter activities in vivo. | Cotransfection of a plasmid expressing hDREF increased luciferase expression directed by each RP gene promoter more than 30% compared with the values obtained without the hDREF-expressing plasmid.

SIGNOR-266083

Q9H6Z4

Q15418

0

phosphorylation

up-regulates quantity

0.319

RSK phosphorylates RanBP3 at Serine 58 residue in vitro and in vivo.RanBP3 phosphorylation increases its affinity towards Ran

SIGNOR-276149

Q12834

P24941

0

phosphorylation

down-regulates activity

0.684

Here we show that cyclin A2-Cdk2 binds and phosphorylates Cdc20 in interphase and this inhibits APC/C-Cdc20 activity.|Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry.

SIGNOR-279322

Q13309

O00755

2

binding

down-regulates activity

0.2

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

SIGNOR-278876

P63092

P08631

2

binding

up-regulates activity

0.2

Galphas and Galphai similarly modulate Hck, another member of Src-family tyrosine kinases.

SIGNOR-256529

P49757

Q6PML9

0

ubiquitination

down-regulates quantity by destabilization

0.2

Lnx functions as a ring type e3 ubiquitin ligase that targets the cell fate determinant numb for ubiquitin-dependent degradation.

SIGNOR-113704

P12694

O14874

0

phosphorylation

down-regulates

0.609

Phosphorylation sites and inactivation of branched-chain alpha-ketoacid dehydrogenase isolated from rat heart, bovine kidney, and rabbit liver, kidney, heart, brain, and skeletal muscle.

SIGNOR-25084

P20962

P04150

1

transcriptional regulation

up-regulates quantity by expression

0.328

Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner

SIGNOR-268460

Q9Y613

P12931

0

phosphorylation

up-regulates activity

0.306

Our results show that only Src can efficiently phosphorylate FHOD1 at Y99 to enable the downstream activation by ROCK.

SIGNOR-276612

Q05209

Q14289

1

dephosphorylation

down-regulates activity

0.544

Inhibition of the catalytic activity of cell adhesion kinase beta by protein-tyrosine phosphatase-pest-mediated dephosphorylation. / dephosphorylation of tyr402 and tyr579/580 by ptp-pest

SIGNOR-107502

P18031

Q14247

1

dephosphorylation

up-regulates activity

0.516

We conclude that Mena INV promotes invadopodium maturation by inhibiting normal dephosphorylation of cortactin at tyrosine 421 by the phosphatase PTP1B.

SIGNOR-277027

P05067

Q9NYY3

0

phosphorylation

up-regulates activity

0.348

Here we show that Polo-like kinase 2 (Plk2), an activity-inducible regulator of homeostatic plasticity, directly binds and phosphorylates threonine-668 and serine-675 of APP in\u00a0vitro and associates with APP in\u00a0vivo.|Plk2 was necessary and sufficient to induce BACE-1-mediated APP amyloidogenic processing following overexcitation, associated intimately with APP, and directly phosphorylated the APP C-terminus.

SIGNOR-279424

P31751

P15336

1

phosphorylation

up-regulates activity

0.426

Taken together, these data suggest that AMPK regulates EC migration through phosphorylation of AKT2, which promotes ATF2 transactivation of MMP-2 during EC migration.|Within this subgroup, we chose AKT2 for analysis because AKT2 phosphorylates activating transcription factor 2 (ATF2) [ xref , xref ].

SIGNOR-280178

P21796

Q07812

2

binding

up-regulates activity

0.584

The recombinant pro-apoptotic proteins Bax and Bak accelerate the opening of VDAC

SIGNOR-249613

Q03001

P10914

0

transcriptional regulation

down-regulates quantity by repression

0.2

Transient transfection studies with BPAG1 promoter-luciferase reporter gene plasmids and IRF1 and IRF2 expression plasmids revealed that IRF1 and IRF2 directly down-regulated BPAG1 gene transcription in cultured normal human epidermal keratinocytes.

SIGNOR-254492

P51587

Q9Y253

2

binding

up-regulates

0.553

Palb2 and brca2 interact with pol_ and are required to sustain the recruitment of pol_ at blocked replication forks. Palb2 and brca2 stimulate pol_-dependent dna synthesis on d loop substrates

SIGNOR-204538

P62993

P04626

0

relocalization

up-regulates

0.85

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

SIGNOR-121968

P52907

Q6JBY9

2

binding

up-regulates

0.667

An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B). Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.

SIGNOR-263088

Q96SB3

Q13009

2

binding

up-regulates quantity

0.422

Spinophilin binding promotes the plasma membrane localization of Tiam1 and enhances the ability of Tiam1 to activate p70 S6 kinase.

SIGNOR-269175

P0DP24

Q8N5S9

2

binding

up-regulates

0.488

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

SIGNOR-266328

P00519

Q7Z434

1

phosphorylation

up-regulates activity

0.453

A phosphotyrosine specific antibody indicated that MAVS was phosphorylated by c-Abl.

SIGNOR-279673

P29474

P31749

0

phosphorylation

up-regulates

0.877

Recently many investigators have shown that protein phosphorylation of enos by several serine/threonine kinases is a critical control step for no production by endothelial cells. Phosphorylation by amp kinase, akt (or protein kinase b), or protein kinase a on serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no.

SIGNOR-112363

P06400

Q00526

0

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

P30305

P68400

0

phosphorylation

up-regulates activity

0.338

Mass spectrometry analysis demonstrates that at least two serine residues, Ser-186 and Ser-187, are phosphorylated in vivo. | Finally, we demonstrate that phosphorylation of CDC25B by protein kinase CK2 increases the catalytic activity of the phosphatase in vitro as well as in vivo.

SIGNOR-250836

P31751

O60346

0

dephosphorylation

down-regulates activity

0.621

The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells.

SIGNOR-248328

Q8N2M8

P00519

0

phosphorylation

up-regulates activity

0.2

In biochemical assays and in Xenopus growth cones we find that Abl kinase activity enhances the association or co-localization of CLASP2 and F-actin, consistent with previous reports of CLASP binding to actin [Tsvetkov et al., ].|In vitro, Abl phosphorylates CLASP with a Km of 1.89 \u00b5M, indicating that CLASP is a bona fide substrate.

SIGNOR-280166

P24941

O94986

0

relocalization

up-regulates activity

0.278

Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome.

SIGNOR-271724

P31644

Q8TAB3

2

binding

up-regulates quantity by stabilization

0.258

Here, we found that PCDH19 binds the alpha subunits of GABAAR and regulates its surface availability and currents in cultured hippocampal neurons. The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated. Here, we identified a new interaction between PCDH19 and GABAA receptor (GABAAR) alpha subunits in the rat brain. PCDH19 shRNA-mediated downregulation reduces GABAAR surface expression and affects the frequency and kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in cultured hippocampal neurons.

SIGNOR-267219

P15531

2

phosphorylation

up-regulates activity

0.2

An acid-stable (nonhistidine) phosphorylation was identified on autophosphorylated purified recombinant Nm23 proteins and [32P]orthophosphate-labeled human breast carcinoma and murine melanoma Nm23. Phosphoamino acid analysis identified serine as the acid-stable phosphorylation and serine 44 as the major site of phosphorylation. The biological relevance of the novel phosphorylation identified herein is suggested by the direct correlation of in vivo Nm23 acid-stable phosphorylation levels, but not Nm23 NDPK activity, with suppression of tumor metastatic potential among control and nm23-1 transfected murine melanoma cells.

SIGNOR-250303

Q9H3D4

Q6ZMZ3

1

transcriptional regulation

up-regulates quantity by expression

0.2

Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by a marked decrease in expression of several nuclear envelope-associated components (Lamin B1, Lamin A/C, Sun1, Nesprin-3, Plectin) compared with controls. Furthermore, chromatin immunoprecipitation-quantitative PCR assay showed enrichment of p63 on Sun1, Syne3, and Plec promoters, suggesting them as p63 targets.

SIGNOR-263280

O43318

P67775

0

dephosphorylation

down-regulates

0.329

Our results demonstrate that pp6 specifically down-regulates tak1 through dephosphorylation of thr-187 in the activation loop, which is likely important for suppressing inflammatory responses via tak1 signaling pathways.

SIGNOR-150369

P19086

P41145

2

binding

up-regulates activity

0.313

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-257105

Q99708

P38398

2

relocalization

up-regulates activity

0.842

DNA damage activates ATM and CHK2 kinases, which mediate phosphorylation of CtIP and BRCA1. Phosphorylated CtIP associates with BRCA1 and with the MRN complex leading to the recruitment of the BRCC complex at the site of DNA damage where HR is initiated.

SIGNOR-263203

P50148

Q5NUL3

2

binding

up-regulates activity

0.449

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-257371

P42345

P30622

1

phosphorylation

up-regulates activity

0.567

By contrast to the phosphorylation of p150 Glued by PKA, inhibition of mTOR by rapamycin inhibited the ability of CLIP-170 to bind to microtubules, suggesting that phosphorylation by mTOR promotes CLIP-170 microtubule binding.|The new study confirms this physical interaction in animal cells and suggests that mTOR phosphorylates CLIP-170 on some, but not all, of the sites that are phosphorylated in vivo.

SIGNOR-279231

O43791

Q9Y6Q9

2

binding

down-regulates quantity by destabilization

0.479

Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations.

SIGNOR-272827

P31751

Q15365

1

phosphorylation

down-regulates activity

0.429

We show that heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) binds a structural, 33-nucleotide TGF-beta-activated translation (BAT) element in the 3' untranslated region of disabled-2 (Dab2) and interleukin-like EMT inducer (ILEI) transcripts, and represses their translation.TGF-beta activation leads to phosphorylation at Ser 43 of hnRNP E1 by protein kinase Bbeta/Akt2, inducing its release from the BAT element and translational activation of Dab2 and ILEI messenger RNAs.

SIGNOR-262625

Q99759

O43379

2

binding

up-regulates quantity by stabilization

0.2

Specifically, we demonstrate that MEKK3 interacts with WDR62 to stabilize WDR62 and regulates JNK activity in a synergic way. On the other hand, JNK activity also regulates the phosphorylation of WDR62 at T1053 in a feedback loop which facilities the recruitment of FBW7 degradation of WDR62

SIGNOR-271714

P60510

P53350

1

dephosphorylation

down-regulates activity

0.416

PPP4C dephosphorylated PLK1 at the S137 site, negatively regulating its activity in the DSB response in early embryonic cells.

SIGNOR-277076

P00519

Q96MU7

1

phosphorylation

down-regulates

0.305

We show that yt521-b is tyrosine phosphorylated by c-abl in the nucleus.We propose that tyrosine phosphorylation causes sequestration of YT521-B in an insoluble nuclear form, which abolishes the ability of YT521-B to change alternative splice sites.

SIGNOR-125167

P13861

2

phosphorylation

up-regulates activity

0.2

RII subunit containing the 'autophosphorylation' site (Ser-95)

SIGNOR-250073

Q16512

Q92974

1

phosphorylation

down-regulates

0.291

Here we identify a region in the carboxyl terminus of gef-h1 that is important for suppression of its guanine nucleotide exchange activity by microtubules. This portion of the protein includes a coiled-coil motif, a proline-rich motif that may interact with src homology 3 domain-containing proteins, and a potential binding site for 14-3-3 proteins. We show that phosphorylation of gef-h1 at ser(885) by pak1 induces 14-3-3 binding to the exchange factor and relocation of 14-3-3 to microtubules.

SIGNOR-122191

P51955

Q68D86

1

phosphorylation

down-regulates activity

0.2

CCDC102B is recruited to the centrosome by C-Nap1 (also known as CEP250) and interacts with the centrosome linker components rootletin and LRRC45. CCDC102B decorates and facilitates the formation of rootletin filaments. Furthermore, CCDC102B is phosphorylated by Nek2A (an isoform encoded by NEK2) and is disassociated from the centrosome at the onset of mitosis.

SIGNOR-275626

P30968

P50148

2

binding

up-regulates activity

0.474

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-257265

P00533

P46108

1

phosphorylation

down-regulates activity

0.74

To address these questions, we have developed an antibody that specifically recognizes the CrkII protein phosphorylated on Tyr221, and we found that the EGF receptor directly phosphorylates CrkII on Tyr221. Furthermore, we observed that the phosphorylation of Tyr221 of CrkII correlated with its dissociation from the EGF receptor, implicating the phosphorylation of Tyr221 in the negative feedback of binding to the EGF receptor.

SIGNOR-251091

Q4VCS5

O95835

0

phosphorylation

up-regulates quantity by stabilization

0.523

Here low serum and high LATS1 activity are found to enhance the levels of the 130-kDa isoform of angiomotin (Amot130) through phosphorylation by LATS1/2 at serine 175, which then forms a binding site for 14-3-3. Such phosphorylation, in turn, enables the ubiquitin ligase atrophin-1 interacting protein (AIP)4 to bind, ubiquitinate, and stabilize Amot130

SIGNOR-275843

Q9Y6K9

O43318

2

binding

up-regulates activity

0.815

This result suggests that ikkgamma/nemo binds to the polyubiquitinated tak1.

SIGNOR-162634

Q96J02

O15350

1

ubiquitination

down-regulates quantity by destabilization

0.566

Collectively, our present findings suggest that MDM2 promotes Itch-mediated degradation of p73 through the interaction with Itch in HeLa cells

SIGNOR-278699

Q9HBW0

P63096

2

binding

up-regulates

0.625

Lysophosphatidic acid (lpa), a major g protein coupled receptor (gpcr)-activating ligand present in serum, elicits growth factor like responses by stimulating specific gpcrs coupled to heterotrimeric g proteins such as g(i), g(q), and g12/13. lpa2 also can couple to the gi/o, g12/13, and gqfamilies.

SIGNOR-84559

P51955

Q99501

1

phosphorylation

up-regulates activity

0.2

Nek2A mediates G2/M phosphorylation of GAS2L1. GAS2L1 and its Ser352 phosphorylation are required for proper spindle organization and chromosome segregation.

SIGNOR-273683