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
O96017	P30304	1	phosphorylation	down-regulates quantity by destabilization	0.843	We show that IR-induced destruction of Cdc25A requires both ATM and the Chk2-mediated phosphorylation of Cdc25A on serine 123.	SIGNOR-106808
Q13315	P04637	1	phosphorylation	up-regulates quantity by stabilization	0.843	In response to ionizing radiation (ir), atm, the gene product mutated in ataxia telangiectasia, stabilizes and activates p53 through phosphorylation of ser15 and (indirectly) ser20. Here we show that phosphorylation of p53 on ser46, a residue important for p53 apoptotic activity, as well as on ser9, in response to ir also is dependent on the atm protein kinase. one pathway involves the phosphorylation of p53 and its negative regulator mdm2 by ataxia telangiectasia mutated (atm) and chk2 causing p53 activation and stabilization.	SIGNOR-115348
P15692	P17948	1	binding	up-regulates	0.843	Vegf exerts its action by binding to vegfr-1 and vegfr-2.	SIGNOR-121132
P43034	Q9GZM8	1	binding	up-regulates activity	0.843	We demonstrate that LIS1 directly interacts with the cytoplasmic dynein heavy chain (CDHC) and NUDEL. LIS1 is required for the proper distribution of NUDEL and cellular components regulated by CDHC function. Reduction of LIS1 leads to mislocalization of NUDEL, CDHC, β-tubulin, and the Golgi complex	SIGNOR-252157
O14757	Q06609	1	phosphorylation	up-regulates	0.843	We demonstrate that chk1 interacts with rad51, and that rad51 is phosphorylated on thr 309 in a chk1-dependent manner	SIGNOR-133375
Q06643	P36941	1	binding	up-regulates activity	0.843	These experiments point toward the lt-alpha 1/beta 2 complex as the predominant membrane form of lt on the lymphocyte surface, and this complex is the primary ligand for the lt-beta receptor.	SIGNOR-35759
P38398	Q99708	2	ubiquitination	up-regulates	0.842	In conclusion, our data show that ctip is a physiological substrate of the brca1 e3 ligase. Brca1 recruits ctip through its c-terminal brct domains and promotes ctip ubiquitination through its n-terminal ring domain. The ubiquitinated ctip is not targeted for degradation. Instead, ubiquitinated ctip binds to chromatin following dna damage and is likely to be involved in dna damage checkpoint control.	SIGNOR-147711
Q9NW38	Q9NVI1	1	ubiquitination	up-regulates activity	0.842	Phosphorylation of FANCD2 and Fanconi anemia core components (broken pink circles) affects the efficiency of, but is not essential for, ID ubiquitination by the FA core complex, together with E1 and UBE2T. Analogously, ubiquitination of FANCD2 (solid orange ovals) is essential for DNA repair, activating the ID complex for chromatin binding	SIGNOR-263266
P49674	O15534	1	phosphorylation	down-regulates quantity by destabilization	0.842	We show here that mPer proteins, negative limbs of the autoregulatory loop, are specific substrates for CKIepsilon and CKIdelta. The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway.	SIGNOR-267997
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
P06493	P30304	2	phosphorylation	up-regulates	0.842	Mitotic stabilization of cdc25a reflects its phosphorylation on ser17 and ser115 by cyclin b-cdk1, modifications required to uncouple cdc25a from its ubiquitin-proteasome-mediated turnover.	SIGNOR-95260
P30304	P06493	2	dephosphorylation	up-regulates activity	0.842	Phosphatase activity of Cdc25A is critical for its activating capacity (data not shown). In this context, it should also be mentioned that Cdc25A is able to activate cyclin B-Cdk1 in vitro	SIGNOR-248480
Q07817	O14727	1	binding	down-regulates activity	0.842	These experiments demonstrate that bcl-xl associates with caspase-9 and apaf-1, and show that bcl-xl inhibits the maturation of caspase-9 mediated by apaf-1.	SIGNOR-56399
P00533	P19174	1	phosphorylation	up-regulates	0.841	We have identified the sites phosphorylated in vitro by epidermal growth factor (egf) receptor kinase in bovine brain phospholipase c-gamma (plc-gamma). They are tyrosine residues 472, 771, 783, and 1254. we propose, therefore, that the phosphorylation of plc-gamma by egf receptor kinase alters its interaction with putative inhibitory proteins and leads to its activation.	SIGNOR-20984
Q99683	Q9UER7	2	phosphorylation	up-regulates	0.841	Our data demonstrated that ask1 controls the cytoplasmic localization of daxx (fig.1). our results indicate that daxx not only activates ask1 but also is a downstream target of ask1 and that accumulated daxx further activates ask1. Thus, the daxx-ask1 positive feedback loop amplifying jnk/p38 signaling plays an important role in the cell-killing effects of stressors, such as tnfalpha.	SIGNOR-188321
Q05513	Q9NPB6	1	phosphorylation	up-regulates quantity by stabilization	0.841	APKC associates and phosphorylates Par6 on S345. aPKC expression stabilizes Par6 protein levels. We show that the aPKC, PKCι, interacts with TGF-β receptors through Par6 and that these proteins localize to the leading edge of migrating cells. Furthermore, Par6 phosphorylation on serine 345 by TGF-β receptors is enhanced in the presence of aPKC. aPKC kinase activity, as well as an association with Par6, were found to be important for Par6 phosphorylation.	SIGNOR-276433
Q9UER7	Q99683	2	binding	up-regulates	0.841	Daxx was found to activate the jnk kinase kinase ask1, and overexpression of a kinase-deficient ask1 mutant inhibited fas- and daxx-induced apoptosis and jnk activation.	SIGNOR-60164
Q13144	P05198	1	guanine nucleotide exchange factor	up-regulates activity	0.84	EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.	SIGNOR-269123
P53350	O60566	1	phosphorylation	up-regulates	0.84	We identify s676 as a plk1-specific phosphorylation site on bubr1. These findings describe the first in vivo verified phosphorylation site for human bubr1, identify plk1 as the kinase responsible for causing the characteristic mitotic bubr1 upshift, and attribute a kt-specific function to the hyperphosphorylated form of bubr1 in the stabilization of kt-mt interactions.	SIGNOR-157646
O60763	Q14789	1	binding	up-regulates activity	0.84	The “cis-golgin tether” is one of the most well-characterized golgin tether complexes. It is composed of the COPI vesicle-associated golgin giantin linked to Golgi membrane-associated GM130 via p115. GM130 is in turn linked to GRASP65 via a PDZ-like domain. GRASP65 is anchored to the Golgi membrane through N-terminal myristoylation as well as through binding to other Golgi proteins [10]. Together, these proteins appear to mediate vesicle tethering at the cis-Golgi membrane.	SIGNOR-261237
Q8N2Q7	P58400	1	binding	up-regulates activity	0.84	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264149
Q9Y2T1	P25054	1	binding	up-regulates	0.84	It has been found that a multiprotein complex assembled by the cytoplasmic component conductin induces degradation of cytoplasmic beta-catenin. The complex includes apc, the serine/threonine kinase gsk3 beta, and beta-catenin, which bind to conductin at distinct domains.	SIGNOR-79944
Q8N2Q7	Q9ULB1	1	binding	up-regulates activity	0.84	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264144
Q9NZ94	Q9ULB1	1	binding	up-regulates activity	0.84	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264142
O95835	P46937	1	phosphorylation	down-regulates quantity by destabilization	0.84	We show that YAP is phosphorylated by Lats on Ser 381 in one of the HXRXXS motifs, and this phosphorylation provides the priming signal for CK1delta/epsilon to phosphorylate a phosphodegron in YAP. The phosphorylated phosphodegron recruits beta-TRCP, leading to YAP ubiquitination and degradation under conditions of elevated Hippo pathway activity, such as cell contact inhibition	SIGNOR-218034
P31749	P38936	1	phosphorylation	up-regulates quantity by stabilization	0.84	Pim-1, PKC, and Akt1 kinases phosphorylate Thr-145 and Ser-146 sites on p21 protein. Phosphorylation at Thr-145 promotes cytoplasmic translocation and stability of p21. Ser-146 phosphorylation mediated by Akt1 enhances p21 stabilization and promotes cell survival.	SIGNOR-157790
Q9NZ94	P58400	1	binding	up-regulates activity	0.84	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264147
Q15596	P04150	1	binding	up-regulates activity	0.839	Here we report that GRIP1 loss in macrophages attenuates glucocorticoid induction of several anti-inflammatory targets, and that GC treatment of quiescent macrophages globally directs GRIP1 toward GR binding sites dominated by palindromic GC response elements (GRE), suggesting a non-redundant GRIP1 function as a GR coactivator.	SIGNOR-256095
P21860	P62993	1	binding	up-regulates	0.839	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. In this study, we identify grb2 as a specific binding partner to tyrosines y1199 and y1268 of erbb3.	SIGNOR-121971
Q14623	Q13635	1	binding	down-regulates activity	0.838	Biochemical analysis of ptch and ptch2 shows that they both bind to all hedgehog family members with similar affinity and that they can form a complex with smo.Current models suggest that binding of Shh to PTCH prevents the normal inhibition of the seven-transmembrane-protein Smoothened (SMO) by PTCH.	SIGNOR-61311
Q15768	P54764	1	binding	up-regulates	0.838	Receptors of the epha group preferentially interact with glycosylphosphatidylinositol (gpi)-linked ligands (of the ephrin-a subclass, which comprises five ligands), while receptors of the ephb group preferentially interact with transmembrane ligands (of the ephrin-b subclass, which comprises three ligands) (table 1). In either case, binding of a ligand results in eph receptor autophosphorylation on tyrosine residues and activation of the kinase activity of the eph receptor	SIGNOR-52621
P15498	P43403	2	binding	up-regulates activity	0.838	In summary, we demonstrate here that Y315 in ZAP-70 is required to interact with the Vav SH2 domain, and is critical for ZAP-70–mediated gene activation.	SIGNOR-274150
P01112	P10398	1	binding	up-regulates	0.838	The raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases.	SIGNOR-175183
P43403	P15498	2	phosphorylation	up-regulates activity	0.838	These results suggest that CBAP may serve as an adaptor or scaffold in the integrin \u03b21/CBAP/ZAP70-containing complex that, upon chemokine treatment, would allow Vav1 or ZAP70 (or both) to adopt an optimal conformation(s) for ZAP70 to phosphorylate Vav1.\|Together, these results suggested that CBAP is an important component in ZAP70 dependent activation of the Vav1 and Rac1 signaling axis.	SIGNOR-278390
Q06124	P04626	1	dephosphorylation	down-regulates	0.838	...which in turn suggests the importance SHP2 dephosphorylation of pTyr992 in EGFR and pTyr1023 in HER2 to mediate signaling.\|More specifically, we show that acidic residues N-terminal to the substrate pTyr in EGFR and HER2 mediate specific binding by the SHP2 active site, leading to blockade of RasGAP binding and optimal signaling by the two receptors.	SIGNOR-262957
Q15746	P24844	1	phosphorylation	up-regulates	0.838	More than a dozen kinases have been reported to phosphorylate the rlcs of nm ii (fig. 2), including myosin light chain kinase (mlck;also known as mylk), rho-associated, coiled coil-containing kinase (rock), citron kinase, leucine zipper interacting kinase (zipk;also known as dapk3) and myotonic dystrophy kinase-related cdc42-binding kinase (mrck;also known as cdc42bp)6,34,45,46. These kinases phosphorylate rlcs on ser19, thr18 or both, to relieve the inhibition imposed on the myosin molecule by unphosphorylated rlcs and the head_head interaction outlined above.	SIGNOR-188797
O94907	Q96MU8	1	binding	up-regulates	0.838	Dkk1 has been shown to inhibitwnt by binding to and antagonizing lrp5/6. Here we show that the transmembrane proteins kremen1 and kremen2 are high-affinity dkk1 receptors that functionally cooperate with dkk1 to blockwnt/betBeta-catenin. Kremen2 forms a ternary complex with dkk1 and lrp6, and induces rapid endocytosis and removal of thewntreceptor lrp6 from the plasma membrane.	SIGNOR-88838
Q9GZQ8	Q13501	1	binding	up-regulates	0.837	Sqstm1/p62 (named a170 in the mouse;hereafter p62) is the first proposed example of such proteins (bj_?_?Rk_?_?Y et al.,2005). It binds polyubiquitinated protein aggregates via its uba domain and interacts with lc3 on the autophagosome/ this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguishable from p62 inclusion bodies and that p62 is required for their formation.	SIGNOR-184255
O43521	Q16611	1	binding	up-regulates	0.837	Bim, and puma bind with high affinity to all pro-survival proteins	SIGNOR-196932
P45983	Q12968	1	phosphorylation	down-regulates	0.837	Jnks directly phosphorylate nuclear factor of activated t-cell (nfat) transcription factors, thus antagonizing the effects of calcium-regulated signaling through the protein phosphatase calcineurin	SIGNOR-118220
Q5VWQ8	Q99683	1	binding	up-regulates activity	0.837	DAB2IP also mediates recruitment of PP2A to ASK1, binding both proteins through its C2 domain; this favors removal of the inhibitory S967 phosphorylation and further activation of ASK1	SIGNOR-254748
Q00987	O15350	1	binding	down-regulates activity	0.837	Since HDM2, a key negative regulator of p53, also binds to and inhibits p73, we asked whether p73 could mediate Nutlin-3-induced apoptosis.	SIGNOR-255470
P01303	P49146	1	binding	up-regulates	0.837	Analogs of npy and pyy have been synthesized that contain a proline residue in position 34 of the molecule, i.e., [leu31, pro34]npy (fuhlendorff et al., 1990) or [pro34]pyy (grandt et al., 1994b), and are much more potent at y1 than y2receptors.	SIGNOR-56568
P47736	P62834	1	binding	down-regulates activity	0.837	Overexpression of Rap1GAP significantly inhibited Rap1 activation, ERK and Akt phosphorylation of HUVECs compared with pcDNA transfection controls	SIGNOR-278054
P01138	P08138	1	binding	up-regulates	0.836	The low affinity neurotrophin receptor p75ntr can mediate cell survival as well as cell death of neural cells by ngf and other neurotrophins.	SIGNOR-76832
Q86VW2	P61586	1	guanine nucleotide exchange factor	up-regulates activity	0.835	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-260544
Q13315	O96017	1	phosphorylation	up-regulates activity	0.835	Phosphorylation and activation of chk2 are ataxia telangiectasia-mutated (atm) dependent in response to ir	SIGNOR-81403
Q96EB6	Q09472	1	deacetylation	down-regulates	0.835	Sirt1 induces deacetylation and repression of p300 itself (81). Mutational analysis demonstrated that sirt1 repression of p300 involves both lysine 1020 and lysine 1024	SIGNOR-182511
Q14116	Q13478	1	binding	up-regulates	0.835	Acpl was required for il-18 responsiveness in terms of nf?B Induction and jnk activation	SIGNOR-60991
O75581	O15169	1	relocalization	down-regulates activity	0.835	The phosphorylation of lrp6 generates a docking site for axin and recruits it to the plasma membrane, where axin is inactivated and/or targeted for degradation by an unknown mechanism.	SIGNOR-148668
P01111	P10398	1	binding	up-regulates	0.835	The raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases.	SIGNOR-175216
Q9GZQ8	Q9NT62	1	binding	up-regulates	0.835	Lc3-i is activated by the same atg7 involved in atg12 conjugation, transferred to atg3, a second e2-like enzyme, and finally conjugated to pe.	SIGNOR-191549
Q14676	O60934	1	binding	up-regulates	0.834	Mdc1 also undergoes phosphorylation by ck2 after dna damage to generate a phospho-motif on mdc1, which binds directly to nbs1.	SIGNOR-184141
P42345	Q9UBS0	1	phosphorylation	up-regulates	0.834	In response to insulin and nutrients, mtorc1, consisting of mtor, raptor (regulatory-associated protein of mtor), and mlst8, is activated and phosphorylates eukaryotic initiation factor 4e-binding protein (4ebp) and p70 s6 kinase to promote protein synthesis and cell size.	SIGNOR-154821
O43307	P60953	1	guanine nucleotide exchange factor	up-regulates activity	0.834	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-260534
P78317	P61956	1	polyubiquitination	down-regulates quantity by destabilization	0.834	Here we demonstrate that the RING-domain-containing ubiquitin E3 ligase, RNF4 (also known as SNURF), targets poly-SUMO-modified proteins for degradation mediated by ubiquitin. RNF4 depletion or proteasome inhibition led to accumulation of mixed, polyubiquitinated, poly-SUMO chains. PML protein accumulated in RNF4-depleted cells and was ubiquitinated by RNF4 in a SUMO-dependent fashion in vitro.RNF4 preferentially binds to and ubiquitinates SUMO-2 polymers over SUMO-2 monomers in vitro	SIGNOR-272640
Q9H4B6	Q13188	2	binding	up-regulates	0.834	Mst is activated by binding of salvador (sav1, sav in drosophila), which is, in turn, also phosphorylated by mst.	SIGNOR-169829
Q92918	O75791	1	phosphorylation	down-regulates activity	0.834	Serine/threonine phosphorylation of the T cell adaptor proteins SLP76 and GADS by HPK1 induces their release from signaling microclusters and subsequent termination of the T cell response.	SIGNOR-279421
Q13188	Q9H4B6	2	phosphorylation	up-regulates	0.834	In vitro phosphorylation experiments indicate that the phosphorylation of Sav by Mst is direct. The stabilizing effect of Mst was much greater on N-terminally truncated hSav mutants, as long as they retained the ability to bind Mst. Mst mutants that lacked the C-terminal coiled-coil domain and were unable to bind to hSav, also failed to stabilize or phosphorylate hSav	SIGNOR-230716
P61586	Q16513	1	binding	up-regulates activity	0.833	PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome.	SIGNOR-275466
Q9NR50	P05198	1	guanine nucleotide exchange factor	up-regulates activity	0.833	EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.	SIGNOR-269126
Q03591	P01024	1	binding	up-regulates activity	0.833	Finally, we have been able to establish that CFHR1 can sterically inhibit the interaction that CFH/CFHL-1 SCR1-4 makes with C3b.\|CFH regulates the alternative pathway of complement in both the fluid phase and on self-surfaces: It competes with complement factor B (CFB) for binding to C3b and C3(H2O) thereby blocking the formation of the pro-convertase complexes, C3bB and C3(H2O)B. It also accelerates the decay of any existing C3bBb or C3(H2O)Bb. \|these data have allowed us to consolidate one possible model of CFHR1-mediated deregulation of CFH/CFHL-1 on an activating surface in which CFHR1 directly competes with or blocks both CFH-binding sites on C3b	SIGNOR-263475
Q8N5C8	O43318	1	binding	up-regulates activity	0.833	We have identified a new binding partner of the tgfbeta (transforming growth factor-beta)-activated protein kinase (tak1), termed tab.two distinct tak1 complexes are present in cells. One comprises tak1 complexed with tab1 and tab2, and the other tak1 complexed with tab1 and tab3 (tak1-binding protein-3). Both complexes are activated in response to tumour necrosis factor-alpha or interleukin-1.	SIGNOR-120325
O43521	Q07812	1	binding	up-regulates activity	0.832	We have shown that the interaction of the bims and bimad isoforms with bax leads to a conformational change in this protein analogous to that triggered by the bh3-only protein bid.We find short peptides representing the alpha-helical bh3 domains of bid or bim are capable of inducing oligomerization of bak and bax to release cytochrome.	SIGNOR-87280
Q9Y2T1	P49841	1	binding	up-regulates activity	0.832	It has been found that a multiprotein complex assembled by the cytoplasmic component conductin induces degradation of cytoplasmic beta-catenin. The complex includes apc, the serine/threonine kinase gsk3 beta, and beta-catenin, which bind to conductin at distinct domains.	SIGNOR-79950
P41221	Q13467	1	binding	up-regulates	0.832	These results identify hfz5 as a receptor for wnt-5a.	SIGNOR-46897
P19438	Q12933	1	null	up-regulates	0.832	We found that TNF-R1-mediated IKK activation requires both RIP and TRAF2 proteins. Although TRAF2 or RIP can be independently recruited to the TNF-R1 complex, neither one of them alone is capable of transducing the TNF signal that leads to IKK activation	SIGNOR-256251
O95631	O95185	1	binding	up-regulates	0.832	We provide evidence that netrin-1 triggers the formation of a receptor complex of dcc and unc5 proteins and simultaneously derepresses the interaction between their cytoplasmic domains, thereby converting dcc-mediated attraction to unc5/dcc-mediated repulsion.	SIGNOR-69047
Q7Z628	P61586	1	guanine nucleotide exchange factor	up-regulates activity	0.832	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-260561
Q7Z434	Q14164	1	binding	up-regulates activity	0.832	After ligand binding, cGAS and RIG-I signal through respective adaptor proteins STING and MAVS to recruit the kinases IKK and TBK1, which then activate the transcription factors NF-κB and interferon regulatory factor 3 (IRF3), respectively.	SIGNOR-260144
P30307	P14635	1	dephosphorylation	up-regulates activity	0.832	Cdc25C is an activator of Cdc2 kinase and dephosphorylates and activates the CyclinB-Cdc2 complex shortly before the entry into the mitosis.	SIGNOR-277099
Q92888	P61586	1	guanine nucleotide exchange factor	up-regulates activity	0.831	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-260528
O00220	Q13158	1	binding	up-regulates	0.831	Fadd binds to ligated trailr1 or trail-r2	SIGNOR-97869
O43541	Q9HCE7	2	binding	up-regulates activity	0.831	Smad6 mediates Tbx6 ubiquitination and proteasomal degradation. Tbx6 forms a ternary complex with Smad6 and Smurf1. Here, we report that Tbx6 interacts directly with Smad6, an inhibitory Smad that antagonizes the BMP signal. This interaction is mediated through the Mad homology 2 (MH2) domain of Smad6 and residues 90-180 of Tbx6. We demonstrate that Smad6 facilitates the degradation of Tbx6 protein through recruitment of Smurf1, a ubiquitin E3 ligase.	SIGNOR-272786
O43683	Q02224	1	relocalization	up-regulates activity	0.831	Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity	SIGNOR-252016
Q9HCE7	O43541	2	relocalization	down-regulates activity	0.831	Smurf1, with its WW domain, specifically binds to the PY motif of Smad6 and transports Smad6 into the cytoplasm.	SIGNOR-105931
Q13315	Q9UQ84	1	phosphorylation	up-regulates	0.83	The phosphorylation of exo1 by atm appears to regulate the activity of exo1 following resection, allowing optimal rad51 loading and the completion of hr repair.	SIGNOR-162304
P30304	P24941	2	dephosphorylation	up-regulates activity	0.83	The phosphatase activity of Cdc25A is necessary for Cdk2 activation, most likely due to dephosphorylation on Tyr-15 and Thr-14 of Cdk2.	SIGNOR-248481
O94921	Q8ND76	2	phosphorylation	down-regulates quantity by destabilization	0.83	Phosphorylation of cyclin Y by CDK14 induces its ubiquitination and degradation\|Phosphorylation of CCNY at Serines 71 and 73 creates a putative phospho-degron that controls its association with an SCF complex	SIGNOR-273007
P24941	P30304	2	phosphorylation	down-regulates	0.83	We show here that dna-responsive checkpoints activate pp2a/b56delta phosphatase complexes to dephosphorylate cdc25 at a site distinct from ser287 (t138), the phosphorylation of which is required for 14-3-3 release.	SIGNOR-150839
Q9Y4K3	Q8IUC6	1	polyubiquitination	up-regulates	0.83	Here, we show that the TRAF family proteins directly bind TICAM-1 and demonstrate that TRAF2 and TRAF6 bind different sites of the N-terminal TICAM-1 and accelerate its polyubiquitination. we speculate that polyubiquitination of TICAM-1 by TRAF2 and TRAF6 is required for TICAM-1 to induce IRF-3 and NF-κB activation. This is supported by the observation that polyubiquitination of TICAM-1 was required for TRAF3-binding to TICAM-1	SIGNOR-271428
Q8ND76	O94921	2	binding	up-regulates	0.83	L63 and its vertebrate homolog pftk are regulated by the membrane tethered g2/m cyclin, cyclin y, which mediates binding to and phosphorylation of lrp6.	SIGNOR-162920
Q15303	P62993	1	binding	up-regulates	0.83	Egfr and erbb4 had several docking sites for grb2, while erbb3 was characterized by six binding sites for pi3k. Egfr has six binding sites for the adapter protein grb2, and erbb4 has five, each with different binding strength.	SIGNOR-146876
P0DP23	Q96RR4	1	binding	up-regulates	0.83	The ca2+-calmodulin-dependent protein kinase (cam kinase) cascade includes three kinases: cam-kinase kinase (camkk);and the cam kinases camki and camkiv, which are phosphorylated and activated by camkk.	SIGNOR-61922
P20827	P21709	1	binding	up-regulates	0.83	The eph family receptors and ligands.	SIGNOR-51932
Q9NZ94	P58401	1	binding	up-regulates activity	0.83	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264157
Q9NZ94	Q9P2S2	1	binding	up-regulates activity	0.83	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264152
O75197	O15169	1	relocalization	down-regulates quantity	0.83	Axin is a protein that interacts with the intracellular domain of LRP-5. LRP-5 active form bind Axin and induce LEF-1 activation by destabilizing Axin and stabilizing beta-catenin.	SIGNOR-236997
P24394	P31785	1	binding	up-regulates	0.83	Il-2r gamma was demonstrated to be a component of the il-4 receptor on the basis of chemical cross-linking data, the ability of il-2r gamma to augment il-4 binding affinity, and the requirement for il-2r gamma in il-4-mediated phosphorylation of insulin receptor substrate-1.	SIGNOR-37362
Q14232	P05198	1	guanine nucleotide exchange factor	up-regulates activity	0.83	EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.	SIGNOR-269124
P30305	P06493	2	dephosphorylation	up-regulates activity	0.829	CDC25B facilitates dephosphorylation of the key cell cycle regulator CDC2 (also called CDK1) at Tyr15 or Thr14, thereby initiating the G 2 /M transition ( xref ).\|CDC25B facilitates dephosphorylation of the key cell cycle regulator CDC2 (also called CDK1) at Tyr15 or Thr14, thereby initiating the G2/M transition ( ).	SIGNOR-276969
P00533	P51692	1	phosphorylation	up-regulates	0.829	Novel activation of stat5b in response to epidermal growth factor. novel activation of stat5b in response to epidermal growth factor.	SIGNOR-113393
Q8N2Q7	Q9Y4C0	1	binding	up-regulates activity	0.829	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264164
Q9P2S2	Q8NFZ4	2	binding	up-regulates activity	0.829	The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites	SIGNOR-265454
P06493	P30305	2	phosphorylation	up-regulates	0.829	Ser(321) is phosphorylated in mitosis by cdk1. The mitotic phosphorylation of ser(321) acts to maintain full activation of cdc25b by disrupting 14-3-3 binding to ser(323) and enhancing the dephosphorylation of ser(323) to block 14-3-3 binding to this site.	SIGNOR-167641
P58401	Q8NFZ4	2	binding	up-regulates activity	0.829	The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites	SIGNOR-265455
Q8NFZ4	P58401	2	binding	up-regulates activity	0.829	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264161
P51148	Q15075	1	binding	up-regulates activity	0.829	The Rab5 effector early endosome antigen 1 (EEA1) is a parallel coiled coil homodimer with an N-terminal C(2)H(2) Zn(2+) finger and a C-terminal FYVE domain. Rab5 binds to independent sites at the N and C terminus of EEA1.\|The results demonstrate that the C(2)H(2) Zn(2+) finger is both essential and sufficient for the N-terminal interaction with Rab5.	SIGNOR-261266
Q8NFZ4	Q9P2S2	2	binding	up-regulates activity	0.829	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264156
Q8N2Q7	P58401	1	binding	up-regulates activity	0.829	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264159

O96017

P30304

1

phosphorylation

down-regulates quantity by destabilization

0.843

We show that IR-induced destruction of Cdc25A requires both ATM and the Chk2-mediated phosphorylation of Cdc25A on serine 123.

SIGNOR-106808

Q13315

P04637

1

phosphorylation

up-regulates quantity by stabilization

0.843

In response to ionizing radiation (ir), atm, the gene product mutated in ataxia telangiectasia, stabilizes and activates p53 through phosphorylation of ser15 and (indirectly) ser20. Here we show that phosphorylation of p53 on ser46, a residue important for p53 apoptotic activity, as well as on ser9, in response to ir also is dependent on the atm protein kinase. one pathway involves the phosphorylation of p53 and its negative regulator mdm2 by ataxia telangiectasia mutated (atm) and chk2 causing p53 activation and stabilization.

SIGNOR-115348

P15692

P17948

1

binding

up-regulates

0.843

Vegf exerts its action by binding to vegfr-1 and vegfr-2.

SIGNOR-121132

P43034

Q9GZM8

1

binding

up-regulates activity

0.843

We demonstrate that LIS1 directly interacts with the cytoplasmic dynein heavy chain (CDHC) and NUDEL. LIS1 is required for the proper distribution of NUDEL and cellular components regulated by CDHC function. Reduction of LIS1 leads to mislocalization of NUDEL, CDHC, β-tubulin, and the Golgi complex

SIGNOR-252157

O14757

Q06609

1

phosphorylation

up-regulates

0.843

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

SIGNOR-133375

Q06643

P36941

1

binding

up-regulates activity

0.843

These experiments point toward the lt-alpha 1/beta 2 complex as the predominant membrane form of lt on the lymphocyte surface, and this complex is the primary ligand for the lt-beta receptor.

SIGNOR-35759

P38398

Q99708

2

ubiquitination

up-regulates

0.842

In conclusion, our data show that ctip is a physiological substrate of the brca1 e3 ligase. Brca1 recruits ctip through its c-terminal brct domains and promotes ctip ubiquitination through its n-terminal ring domain. The ubiquitinated ctip is not targeted for degradation. Instead, ubiquitinated ctip binds to chromatin following dna damage and is likely to be involved in dna damage checkpoint control.

SIGNOR-147711

Q9NW38

Q9NVI1

1

ubiquitination

up-regulates activity

0.842

Phosphorylation of FANCD2 and Fanconi anemia core components (broken pink circles) affects the efficiency of, but is not essential for, ID ubiquitination by the FA core complex, together with E1 and UBE2T. Analogously, ubiquitination of FANCD2 (solid orange ovals) is essential for DNA repair, activating the ID complex for chromatin binding

SIGNOR-263266

P49674

O15534

1

phosphorylation

down-regulates quantity by destabilization

0.842

We show here that mPer proteins, negative limbs of the autoregulatory loop, are specific substrates for CKIepsilon and CKIdelta. The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway.

SIGNOR-267997

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

P06493

P30304

2

phosphorylation

up-regulates

0.842

Mitotic stabilization of cdc25a reflects its phosphorylation on ser17 and ser115 by cyclin b-cdk1, modifications required to uncouple cdc25a from its ubiquitin-proteasome-mediated turnover.

SIGNOR-95260

P30304

P06493

2

dephosphorylation

up-regulates activity

0.842

Phosphatase activity of Cdc25A is critical for its activating capacity (data not shown). In this context, it should also be mentioned that Cdc25A is able to activate cyclin B-Cdk1 in vitro

SIGNOR-248480

Q07817

O14727

1

binding

down-regulates activity

0.842

These experiments demonstrate that bcl-xl associates with caspase-9 and apaf-1, and show that bcl-xl inhibits the maturation of caspase-9 mediated by apaf-1.

SIGNOR-56399

P00533

P19174

1

phosphorylation

up-regulates

0.841

We have identified the sites phosphorylated in vitro by epidermal growth factor (egf) receptor kinase in bovine brain phospholipase c-gamma (plc-gamma). They are tyrosine residues 472, 771, 783, and 1254. we propose, therefore, that the phosphorylation of plc-gamma by egf receptor kinase alters its interaction with putative inhibitory proteins and leads to its activation.

SIGNOR-20984

Q99683

Q9UER7

2

phosphorylation

up-regulates

0.841

Our data demonstrated that ask1 controls the cytoplasmic localization of daxx (fig.1). our results indicate that daxx not only activates ask1 but also is a downstream target of ask1 and that accumulated daxx further activates ask1. Thus, the daxx-ask1 positive feedback loop amplifying jnk/p38 signaling plays an important role in the cell-killing effects of stressors, such as tnfalpha.

SIGNOR-188321

Q05513

Q9NPB6

1

phosphorylation

up-regulates quantity by stabilization

0.841

APKC associates and phosphorylates Par6 on S345. aPKC expression stabilizes Par6 protein levels. We show that the aPKC, PKCι, interacts with TGF-β receptors through Par6 and that these proteins localize to the leading edge of migrating cells. Furthermore, Par6 phosphorylation on serine 345 by TGF-β receptors is enhanced in the presence of aPKC. aPKC kinase activity, as well as an association with Par6, were found to be important for Par6 phosphorylation.

SIGNOR-276433

Q9UER7

Q99683

2

binding

up-regulates

0.841

Daxx was found to activate the jnk kinase kinase ask1, and overexpression of a kinase-deficient ask1 mutant inhibited fas- and daxx-induced apoptosis and jnk activation.

SIGNOR-60164

Q13144

P05198

1

guanine nucleotide exchange factor

up-regulates activity

0.84

EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.

SIGNOR-269123

P53350

O60566

1

phosphorylation

up-regulates

0.84

We identify s676 as a plk1-specific phosphorylation site on bubr1. These findings describe the first in vivo verified phosphorylation site for human bubr1, identify plk1 as the kinase responsible for causing the characteristic mitotic bubr1 upshift, and attribute a kt-specific function to the hyperphosphorylated form of bubr1 in the stabilization of kt-mt interactions.

SIGNOR-157646

O60763

Q14789

1

binding

up-regulates activity

0.84

The “cis-golgin tether” is one of the most well-characterized golgin tether complexes. It is composed of the COPI vesicle-associated golgin giantin linked to Golgi membrane-associated GM130 via p115. GM130 is in turn linked to GRASP65 via a PDZ-like domain. GRASP65 is anchored to the Golgi membrane through N-terminal myristoylation as well as through binding to other Golgi proteins [10]. Together, these proteins appear to mediate vesicle tethering at the cis-Golgi membrane.

SIGNOR-261237

Q8N2Q7

P58400

1

binding

up-regulates activity

0.84

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264149

Q9Y2T1

P25054

1

binding

up-regulates

0.84

It has been found that a multiprotein complex assembled by the cytoplasmic component conductin induces degradation of cytoplasmic beta-catenin. The complex includes apc, the serine/threonine kinase gsk3 beta, and beta-catenin, which bind to conductin at distinct domains.

SIGNOR-79944

Q8N2Q7

Q9ULB1

1

binding

up-regulates activity

0.84

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264144

Q9NZ94

Q9ULB1

1

binding

up-regulates activity

0.84

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264142

O95835

P46937

1

phosphorylation

down-regulates quantity by destabilization

0.84

We show that YAP is phosphorylated by Lats on Ser 381 in one of the HXRXXS motifs, and this phosphorylation provides the priming signal for CK1delta/epsilon to phosphorylate a phosphodegron in YAP. The phosphorylated phosphodegron recruits beta-TRCP, leading to YAP ubiquitination and degradation under conditions of elevated Hippo pathway activity, such as cell contact inhibition

SIGNOR-218034

P31749

P38936

1

phosphorylation

up-regulates quantity by stabilization

0.84

Pim-1, PKC, and Akt1 kinases phosphorylate Thr-145 and Ser-146 sites on p21 protein. Phosphorylation at Thr-145 promotes cytoplasmic translocation and stability of p21. Ser-146 phosphorylation mediated by Akt1 enhances p21 stabilization and promotes cell survival.

SIGNOR-157790

Q9NZ94

P58400

1

binding

up-regulates activity

0.84

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264147

Q15596

P04150

1

binding

up-regulates activity

0.839

Here we report that GRIP1 loss in macrophages attenuates glucocorticoid induction of several anti-inflammatory targets, and that GC treatment of quiescent macrophages globally directs GRIP1 toward GR binding sites dominated by palindromic GC response elements (GRE), suggesting a non-redundant GRIP1 function as a GR coactivator.

SIGNOR-256095

P21860

P62993

1

binding

up-regulates

0.839

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. In this study, we identify grb2 as a specific binding partner to tyrosines y1199 and y1268 of erbb3.

SIGNOR-121971

Q14623

Q13635

1

binding

down-regulates activity

0.838

Biochemical analysis of ptch and ptch2 shows that they both bind to all hedgehog family members with similar affinity and that they can form a complex with smo.Current models suggest that binding of Shh to PTCH prevents the normal inhibition of the seven-transmembrane-protein Smoothened (SMO) by PTCH.

SIGNOR-61311

Q15768

P54764

1

binding

up-regulates

0.838

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

SIGNOR-52621

P15498

P43403

2

binding

up-regulates activity

0.838

In summary, we demonstrate here that Y315 in ZAP-70 is required to interact with the Vav SH2 domain, and is critical for ZAP-70–mediated gene activation.

SIGNOR-274150

P01112

P10398

1

binding

up-regulates

0.838

The raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases.

SIGNOR-175183

P43403

P15498

2

phosphorylation

up-regulates activity

0.838

These results suggest that CBAP may serve as an adaptor or scaffold in the integrin \u03b21/CBAP/ZAP70-containing complex that, upon chemokine treatment, would allow Vav1 or ZAP70 (or both) to adopt an optimal conformation(s) for ZAP70 to phosphorylate Vav1.|Together, these results suggested that CBAP is an important component in ZAP70 dependent activation of the Vav1 and Rac1 signaling axis.

SIGNOR-278390

Q06124

P04626

1

dephosphorylation

down-regulates

0.838

...which in turn suggests the importance SHP2 dephosphorylation of pTyr992 in EGFR and pTyr1023 in HER2 to mediate signaling.|More specifically, we show that acidic residues N-terminal to the substrate pTyr in EGFR and HER2 mediate specific binding by the SHP2 active site, leading to blockade of RasGAP binding and optimal signaling by the two receptors.

SIGNOR-262957

Q15746

P24844

1

phosphorylation

up-regulates

0.838

More than a dozen kinases have been reported to phosphorylate the rlcs of nm ii (fig. 2), including myosin light chain kinase (mlck;also known as mylk), rho-associated, coiled coil-containing kinase (rock), citron kinase, leucine zipper interacting kinase (zipk;also known as dapk3) and myotonic dystrophy kinase-related cdc42-binding kinase (mrck;also known as cdc42bp)6,34,45,46. These kinases phosphorylate rlcs on ser19, thr18 or both, to relieve the inhibition imposed on the myosin molecule by unphosphorylated rlcs and the head_head interaction outlined above.

SIGNOR-188797

O94907

Q96MU8

1

binding

up-regulates

0.838

Dkk1 has been shown to inhibitwnt by binding to and antagonizing lrp5/6. Here we show that the transmembrane proteins kremen1 and kremen2 are high-affinity dkk1 receptors that functionally cooperate with dkk1 to blockwnt/betBeta-catenin. Kremen2 forms a ternary complex with dkk1 and lrp6, and induces rapid endocytosis and removal of thewntreceptor lrp6 from the plasma membrane.

SIGNOR-88838

Q9GZQ8

Q13501

1

binding

up-regulates

0.837

Sqstm1/p62 (named a170 in the mouse;hereafter p62) is the first proposed example of such proteins (bj_?_?Rk_?_?Y et al.,2005). It binds polyubiquitinated protein aggregates via its uba domain and interacts with lc3 on the autophagosome/ this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguishable from p62 inclusion bodies and that p62 is required for their formation.

SIGNOR-184255

O43521

Q16611

1

binding

up-regulates

0.837

Bim, and puma bind with high affinity to all pro-survival proteins

SIGNOR-196932

P45983

Q12968

1

phosphorylation

down-regulates

0.837

Jnks directly phosphorylate nuclear factor of activated t-cell (nfat) transcription factors, thus antagonizing the effects of calcium-regulated signaling through the protein phosphatase calcineurin

SIGNOR-118220

Q5VWQ8

Q99683

1

binding

up-regulates activity

0.837

DAB2IP also mediates recruitment of PP2A to ASK1, binding both proteins through its C2 domain; this favors removal of the inhibitory S967 phosphorylation and further activation of ASK1

SIGNOR-254748

Q00987

O15350

1

binding

down-regulates activity

0.837

Since HDM2, a key negative regulator of p53, also binds to and inhibits p73, we asked whether p73 could mediate Nutlin-3-induced apoptosis.

SIGNOR-255470

P01303

P49146

1

binding

up-regulates

0.837

Analogs of npy and pyy have been synthesized that contain a proline residue in position 34 of the molecule, i.e., [leu31, pro34]npy (fuhlendorff et al., 1990) or [pro34]pyy (grandt et al., 1994b), and are much more potent at y1 than y2receptors.

SIGNOR-56568

P47736

P62834

1

binding

down-regulates activity

0.837

Overexpression of Rap1GAP significantly inhibited Rap1 activation, ERK and Akt phosphorylation of HUVECs compared with pcDNA transfection controls

SIGNOR-278054

P01138

P08138

1

binding

up-regulates

0.836

The low affinity neurotrophin receptor p75ntr can mediate cell survival as well as cell death of neural cells by ngf and other neurotrophins.

SIGNOR-76832

Q86VW2

P61586

1

guanine nucleotide exchange factor

up-regulates activity

0.835

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-260544

Q13315

O96017

1

phosphorylation

up-regulates activity

0.835

Phosphorylation and activation of chk2 are ataxia telangiectasia-mutated (atm) dependent in response to ir

SIGNOR-81403

Q96EB6

Q09472

1

deacetylation

down-regulates

0.835

Sirt1 induces deacetylation and repression of p300 itself (81). Mutational analysis demonstrated that sirt1 repression of p300 involves both lysine 1020 and lysine 1024

SIGNOR-182511

Q14116

Q13478

1

binding

up-regulates

0.835

Acpl was required for il-18 responsiveness in terms of nf?B Induction and jnk activation

SIGNOR-60991

O75581

O15169

1

relocalization

down-regulates activity

0.835

The phosphorylation of lrp6 generates a docking site for axin and recruits it to the plasma membrane, where axin is inactivated and/or targeted for degradation by an unknown mechanism.

SIGNOR-148668

P01111

P10398

1

binding

up-regulates

0.835

The raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases.

SIGNOR-175216

Q9GZQ8

Q9NT62

1

binding

up-regulates

0.835

Lc3-i is activated by the same atg7 involved in atg12 conjugation, transferred to atg3, a second e2-like enzyme, and finally conjugated to pe.

SIGNOR-191549

Q14676

O60934

1

binding

up-regulates

0.834

Mdc1 also undergoes phosphorylation by ck2 after dna damage to generate a phospho-motif on mdc1, which binds directly to nbs1.

SIGNOR-184141

P42345

Q9UBS0

1

phosphorylation

up-regulates

0.834

In response to insulin and nutrients, mtorc1, consisting of mtor, raptor (regulatory-associated protein of mtor), and mlst8, is activated and phosphorylates eukaryotic initiation factor 4e-binding protein (4ebp) and p70 s6 kinase to promote protein synthesis and cell size.

SIGNOR-154821

O43307

P60953

1

guanine nucleotide exchange factor

up-regulates activity

0.834

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-260534

P78317

P61956

1

polyubiquitination

down-regulates quantity by destabilization

0.834

Here we demonstrate that the RING-domain-containing ubiquitin E3 ligase, RNF4 (also known as SNURF), targets poly-SUMO-modified proteins for degradation mediated by ubiquitin. RNF4 depletion or proteasome inhibition led to accumulation of mixed, polyubiquitinated, poly-SUMO chains. PML protein accumulated in RNF4-depleted cells and was ubiquitinated by RNF4 in a SUMO-dependent fashion in vitro.RNF4 preferentially binds to and ubiquitinates SUMO-2 polymers over SUMO-2 monomers in vitro

SIGNOR-272640

Q9H4B6

Q13188

2

binding

up-regulates

0.834

Mst is activated by binding of salvador (sav1, sav in drosophila), which is, in turn, also phosphorylated by mst.

SIGNOR-169829

Q92918

O75791

1

phosphorylation

down-regulates activity

0.834

Serine/threonine phosphorylation of the T cell adaptor proteins SLP76 and GADS by HPK1 induces their release from signaling microclusters and subsequent termination of the T cell response.

SIGNOR-279421

Q13188

Q9H4B6

2

phosphorylation

up-regulates

0.834

In vitro phosphorylation experiments indicate that the phosphorylation of Sav by Mst is direct. The stabilizing effect of Mst was much greater on N-terminally truncated hSav mutants, as long as they retained the ability to bind Mst. Mst mutants that lacked the C-terminal coiled-coil domain and were unable to bind to hSav, also failed to stabilize or phosphorylate hSav

SIGNOR-230716

P61586

Q16513

1

binding

up-regulates activity

0.833

PKNs bind to human pyrin and phosphorylate S208 and S242. Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome.

SIGNOR-275466

Q9NR50

P05198

1

guanine nucleotide exchange factor

up-regulates activity

0.833

EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.

SIGNOR-269126

Q03591

P01024

1

binding

up-regulates activity

0.833

Finally, we have been able to establish that CFHR1 can sterically inhibit the interaction that CFH/CFHL-1 SCR1-4 makes with C3b.|CFH regulates the alternative pathway of complement in both the fluid phase and on self-surfaces: It competes with complement factor B (CFB) for binding to C3b and C3(H2O) thereby blocking the formation of the pro-convertase complexes, C3bB and C3(H2O)B. It also accelerates the decay of any existing C3bBb or C3(H2O)Bb. |these data have allowed us to consolidate one possible model of CFHR1-mediated deregulation of CFH/CFHL-1 on an activating surface in which CFHR1 directly competes with or blocks both CFH-binding sites on C3b

SIGNOR-263475

Q8N5C8

O43318

1

binding

up-regulates activity

0.833

We have identified a new binding partner of the tgfbeta (transforming growth factor-beta)-activated protein kinase (tak1), termed tab.two distinct tak1 complexes are present in cells. One comprises tak1 complexed with tab1 and tab2, and the other tak1 complexed with tab1 and tab3 (tak1-binding protein-3). Both complexes are activated in response to tumour necrosis factor-alpha or interleukin-1.

SIGNOR-120325

O43521

Q07812

1

binding

up-regulates activity

0.832

We have shown that the interaction of the bims and bimad isoforms with bax leads to a conformational change in this protein analogous to that triggered by the bh3-only protein bid.We find short peptides representing the alpha-helical bh3 domains of bid or bim are capable of inducing oligomerization of bak and bax to release cytochrome.

SIGNOR-87280

Q9Y2T1

P49841

1

binding

up-regulates activity

0.832

It has been found that a multiprotein complex assembled by the cytoplasmic component conductin induces degradation of cytoplasmic beta-catenin. The complex includes apc, the serine/threonine kinase gsk3 beta, and beta-catenin, which bind to conductin at distinct domains.

SIGNOR-79950

P41221

Q13467

1

binding

up-regulates

0.832

These results identify hfz5 as a receptor for wnt-5a.

SIGNOR-46897

P19438

Q12933

1

null

up-regulates

0.832

We found that TNF-R1-mediated IKK activation requires both RIP and TRAF2 proteins. Although TRAF2 or RIP can be independently recruited to the TNF-R1 complex, neither one of them alone is capable of transducing the TNF signal that leads to IKK activation

SIGNOR-256251

O95631

O95185

1

binding

up-regulates

0.832

We provide evidence that netrin-1 triggers the formation of a receptor complex of dcc and unc5 proteins and simultaneously derepresses the interaction between their cytoplasmic domains, thereby converting dcc-mediated attraction to unc5/dcc-mediated repulsion.

SIGNOR-69047

Q7Z628

P61586

1

guanine nucleotide exchange factor

up-regulates activity

0.832

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-260561

Q7Z434

Q14164

1

binding

up-regulates activity

0.832

After ligand binding, cGAS and RIG-I signal through respective adaptor proteins STING and MAVS to recruit the kinases IKK and TBK1, which then activate the transcription factors NF-κB and interferon regulatory factor 3 (IRF3), respectively.

SIGNOR-260144

P30307

P14635

1

dephosphorylation

up-regulates activity

0.832

Cdc25C is an activator of Cdc2 kinase and dephosphorylates and activates the CyclinB-Cdc2 complex shortly before the entry into the mitosis.

SIGNOR-277099

Q92888

P61586

1

guanine nucleotide exchange factor

up-regulates activity

0.831

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-260528

O00220

Q13158

1

binding

up-regulates

0.831

Fadd binds to ligated trailr1 or trail-r2

SIGNOR-97869

O43541

Q9HCE7

2

binding

up-regulates activity

0.831

Smad6 mediates Tbx6 ubiquitination and proteasomal degradation. Tbx6 forms a ternary complex with Smad6 and Smurf1. Here, we report that Tbx6 interacts directly with Smad6, an inhibitory Smad that antagonizes the BMP signal. This interaction is mediated through the Mad homology 2 (MH2) domain of Smad6 and residues 90-180 of Tbx6. We demonstrate that Smad6 facilitates the degradation of Tbx6 protein through recruitment of Smurf1, a ubiquitin E3 ligase.

SIGNOR-272786

O43683

Q02224

1

relocalization

up-regulates activity

0.831

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

SIGNOR-252016

Q9HCE7

O43541

2

relocalization

down-regulates activity

0.831

Smurf1, with its WW domain, specifically binds to the PY motif of Smad6 and transports Smad6 into the cytoplasm.

SIGNOR-105931

Q13315

Q9UQ84

1

phosphorylation

up-regulates

0.83

The phosphorylation of exo1 by atm appears to regulate the activity of exo1 following resection, allowing optimal rad51 loading and the completion of hr repair.

SIGNOR-162304

P30304

P24941

2

dephosphorylation

up-regulates activity

0.83

The phosphatase activity of Cdc25A is necessary for Cdk2 activation, most likely due to dephosphorylation on Tyr-15 and Thr-14 of Cdk2.

SIGNOR-248481

O94921

Q8ND76

2

phosphorylation

down-regulates quantity by destabilization

0.83

Phosphorylation of cyclin Y by CDK14 induces its ubiquitination and degradation|Phosphorylation of CCNY at Serines 71 and 73 creates a putative phospho-degron that controls its association with an SCF complex

SIGNOR-273007

P24941

P30304

2

phosphorylation

down-regulates

0.83

We show here that dna-responsive checkpoints activate pp2a/b56delta phosphatase complexes to dephosphorylate cdc25 at a site distinct from ser287 (t138), the phosphorylation of which is required for 14-3-3 release.

SIGNOR-150839

Q9Y4K3

Q8IUC6

1

polyubiquitination

up-regulates

0.83

Here, we show that the TRAF family proteins directly bind TICAM-1 and demonstrate that TRAF2 and TRAF6 bind different sites of the N-terminal TICAM-1 and accelerate its polyubiquitination. we speculate that polyubiquitination of TICAM-1 by TRAF2 and TRAF6 is required for TICAM-1 to induce IRF-3 and NF-κB activation. This is supported by the observation that polyubiquitination of TICAM-1 was required for TRAF3-binding to TICAM-1

SIGNOR-271428

Q8ND76

O94921

2

binding

up-regulates

0.83

L63 and its vertebrate homolog pftk are regulated by the membrane tethered g2/m cyclin, cyclin y, which mediates binding to and phosphorylation of lrp6.

SIGNOR-162920

Q15303

P62993

1

binding

up-regulates

0.83

Egfr and erbb4 had several docking sites for grb2, while erbb3 was characterized by six binding sites for pi3k. Egfr has six binding sites for the adapter protein grb2, and erbb4 has five, each with different binding strength.

SIGNOR-146876

P0DP23

Q96RR4

1

binding

up-regulates

0.83

The ca2+-calmodulin-dependent protein kinase (cam kinase) cascade includes three kinases: cam-kinase kinase (camkk);and the cam kinases camki and camkiv, which are phosphorylated and activated by camkk.

SIGNOR-61922

P20827

P21709

1

binding

up-regulates

0.83

The eph family receptors and ligands.

SIGNOR-51932

Q9NZ94

P58401

1

binding

up-regulates activity

0.83

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264157

Q9NZ94

Q9P2S2

1

binding

up-regulates activity

0.83

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264152

O75197

O15169

1

relocalization

down-regulates quantity

0.83

Axin is a protein that interacts with the intracellular domain of LRP-5. LRP-5 active form bind Axin and induce LEF-1 activation by destabilizing Axin and stabilizing beta-catenin.

SIGNOR-236997

P24394

P31785

1

binding

up-regulates

0.83

Il-2r gamma was demonstrated to be a component of the il-4 receptor on the basis of chemical cross-linking data, the ability of il-2r gamma to augment il-4 binding affinity, and the requirement for il-2r gamma in il-4-mediated phosphorylation of insulin receptor substrate-1.

SIGNOR-37362

Q14232

P05198

1

guanine nucleotide exchange factor

up-regulates activity

0.83

EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.

SIGNOR-269124

P30305

P06493

2

dephosphorylation

up-regulates activity

0.829

CDC25B facilitates dephosphorylation of the key cell cycle regulator CDC2 (also called CDK1) at Tyr15 or Thr14, thereby initiating the G 2 /M transition ( xref ).|CDC25B facilitates dephosphorylation of the key cell cycle regulator CDC2 (also called CDK1) at Tyr15 or Thr14, thereby initiating the G2/M transition ( ).

SIGNOR-276969

P00533

P51692

1

phosphorylation

up-regulates

0.829

Novel activation of stat5b in response to epidermal growth factor. novel activation of stat5b in response to epidermal growth factor.

SIGNOR-113393

Q8N2Q7

Q9Y4C0

1

binding

up-regulates activity

0.829

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264164

Q9P2S2

Q8NFZ4

2

binding

up-regulates activity

0.829

The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites

SIGNOR-265454

P06493

P30305

2

phosphorylation

up-regulates

0.829

Ser(321) is phosphorylated in mitosis by cdk1. The mitotic phosphorylation of ser(321) acts to maintain full activation of cdc25b by disrupting 14-3-3 binding to ser(323) and enhancing the dephosphorylation of ser(323) to block 14-3-3 binding to this site.

SIGNOR-167641

P58401

Q8NFZ4

2

binding

up-regulates activity

0.829

The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites

SIGNOR-265455

Q8NFZ4

P58401

2

binding

up-regulates activity

0.829

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264161

P51148

Q15075

1

binding

up-regulates activity

0.829

The Rab5 effector early endosome antigen 1 (EEA1) is a parallel coiled coil homodimer with an N-terminal C(2)H(2) Zn(2+) finger and a C-terminal FYVE domain. Rab5 binds to independent sites at the N and C terminus of EEA1.|The results demonstrate that the C(2)H(2) Zn(2+) finger is both essential and sufficient for the N-terminal interaction with Rab5.

SIGNOR-261266

Q8NFZ4

Q9P2S2

2

binding

up-regulates activity

0.829

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264156

Q8N2Q7

P58401

1

binding

up-regulates activity

0.829

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264159