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
Q08211	Q9BRS8	2	binding	up-regulates activity	0.41	La ribonucleoprotein domain family member 6 (LARP6) is the protein that binds 5' SL with high affinity and specificity and coordinates their translation. Here we show that RNA helicase A (RHA) is tethered to the 5' SL of collagen mRNAs by interaction with the C-terminal domain of LARP6.	SIGNOR-273500
Q9BYP7	P55011	1	phosphorylation	up-regulates activity	0.525	We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities\|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs	SIGNOR-264625
Q13188	Q9UL54	0	phosphorylation	up-regulates	0.274	In addition, the thousand-and-one (tao) amino acids kinase or taok13 has been shown to directly phosphorylate and activate hpo or mst1/2.	SIGNOR-201327
P06241	Q16620	2	binding	up-regulates	0.381	All these data suggest the involvement of fyn in the neurotrophin signal transduction pathways downstream of trkb. We investigated whether fyn is involved in the trk-dependent signal transduction pathways of neurotrophin. The fyn-src homology domain 2 (sh2) was observed to associate in vitro with the intracellular domain of trkb (icd-trkb).	SIGNOR-58424
O14757	O15151	1	phosphorylation	down-regulates activity	0.52	MDMX is a direct substrate for Chk1 and Chk2 in vitro. Phosphorylation of MDMX leads to increased binding to MDM2 and more efficient ubiquitination, providing an explanation for the enhanced degradation of MDMX after DNA damage. \| Western blot showed that Chk1 modified S342 and S367, but with strong preference for S342.	SIGNOR-250770
Q92538	P68400	0	phosphorylation	down-regulates quantity by destabilization	0.2	We show that, in mitosis, GBF1 is phosphorylated on Ser292 and Ser297 by casein kinase-2 allowing recognition by the F-box protein βTrCP. GBF1 interaction with βTrCP recruits GBF1 to the SCFβTrCP ubiquitin ligase complex, triggering its degradation.	SIGNOR-277398
Q9BZL4	P54646	0	phosphorylation	down-regulates	0.259	Ampk-induced phosphorylation is necessary for ppp1r12c interaction with 14-3-3 and phosphorylation of myosin regulatory light chain. Both ampk activity and ppp1r12c phosphorylation are increased in mitotic cells and are important for mitosis completion. The interaction between ppp1r12c and 14-3-3_ may inactivate the ppp1r12c-containing phosphatase complex in vivo.	SIGNOR-195148
P05412	P98066	1	transcriptional regulation	up-regulates quantity by expression	0.308	Tumor necrosis factor (TNF)-stimulated gene 6 (TSG-6) encodes a protein expressed during inflammation. We have previously shown that transcription factors of the NF-IL6 and AP-1 families cooperatively modulate activation of the TSG-6 gene by TNF or interleukin 1 (IL-1) through a promoter region that contains an NF-IL6 site (-106 to -114) and an AP-1 element	SIGNOR-254052
P78352	Q9HCJ2	2	binding	up-regulates activity	0.365	A possible function for the NGL–PSD-95 interaction is to couple trans-synaptic adhesion events to the recruitment of PSD-95 and other PSD-95-associated postsynaptic proteins. PSD-95 and liprin-α may be key synaptic scaffolding proteins that couple trans-synaptic adhesions to the assembly of synaptic proteins/vesicles	SIGNOR-264050
P11473	O60315	0	transcriptional regulation	up-regulates quantity by expression	0.2	ZEB, a Krüppel-type transcription factor known to repress the transcription of several genes, binds to two sites within the VDR promoter and activates the transcription of this receptor in a cell-specific manner. Transfection of ZEB into SW620 colon carcinoma cells results in an up-regulation of the expression of endogenous VDR, confirming the role of ZEB in the transcriptional activation of the VDR gene.	SIGNOR-268954
P08754	P30556	2	binding	up-regulates activity	0.25	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256881
Q13144	P68400	0	phosphorylation	up-regulates activity	0.386	Two conserved sites (Ser712/713) are phosphorylated by casein kinase 2. They lie at the extreme C-terminus and are required for the interaction of eIF2Bepsilon with its substrate, eIF2, in vivo and for eIF2B activity in vitro.	SIGNOR-250859
P0C2W1	O15350	2	binding	down-regulates quantity by destabilization	0.597	The F-box protein FBXO45 promotes the proteasome-dependent degradation of p73.Importantly, SCFFBXO45 ubiquitylates p73 both in vivo and in vitro. Expression of Cul1 dominant negative mutant, but not Cul2, Cul3, Cul4 and Cul5 dominant negative mutants, increased p73 levels (Figure 1c) to an extent similar to that observed in the ts41 cell line at not permissive temperature, suggesting that a Cul1-associated activity is required for p73 protein stability.	SIGNOR-271876
P31269	O00470	2	binding	up-regulates activity	0.62	We now show that the Hoxa-9 protein physically interacts with Meis1 proteins. Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.	SIGNOR-241162
Q12888	P06493	0	phosphorylation	down-regulates activity	0.599	Nuclear import of 53BP1 is required for proper localization of 53BP1 and maintenance of genome integrity. 53BP1 has a classical bipartite nuclear localization signal (NLS) of sequence 1666-GKRKLITSEEERSPAKRGRKS-1686. Ser1678 within the 53BP1 NLS can be phosphorylated by CDK1/cyclin B, and a phosphomimetic substitution of Ser1678 with aspartate has been shown to negatively regulate nuclear import of 53BP1.	SIGNOR-264412
P63000	P36897	0	null	up-regulates activity	0.28	Thus, TGF-_1 rapidly stimulates activity of both RhoA and Rac1 and this activation requires ALK5/T_RI kinase activity.	SIGNOR-227496
P17931	P42684	0	phosphorylation	up-regulates	0.2	The sh (src homology)3 domains of c-abl/arg bind to a p(80)gppsgp motif of gal3, and tyr79 and tyr118 are the major tyrosine phosphorylation sites. A consequence of this interaction and phosphorylation is the significant impairment of chaperone-mediated autophagy of gal3.	SIGNOR-163747
Q13464	Q14457	1	phosphorylation	up-regulates activity	0.415	Beclin1 is phosphorylated by ROCK1 at T119.	SIGNOR-278198
P11387	P06493	0	phosphorylation	up-regulates activity	0.349	In vitro kinase assays demonstrated that Ser(10) can be phosphorylated by casein kinase II, Ser(21) can be phosphorylated by protein kinase Calpha, and Ser(112) and Ser(394) can be phosphorylated by Cdk1.Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells.	SIGNOR-276157
Q9UHD2	A7MCY6	0	relocalization	up-regulates activity	0.603	TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation	SIGNOR-272469
Q04724	Q9UJU2	2	binding	down-regulates activity	0.689	Our data shows that Groucho/TLE repression requires two sites of interaction in LEF-1 and that a central, conserved amino acid sequence within the primary region (F S/T/P/xx y I/L/V) is critical.	SIGNOR-260109
Q14934	Q08209	0	dephosphorylation	up-regulates	0.566	Calcineurin directly dephosphorylates nfat resulting in the nuclear import of nfat.	SIGNOR-176379
Q16611	P99999	1	relocalization	up-regulates	0.566	Allosteric activation of bak induces its intramembranous oligomerization into a proposed pore for cytochrome c efflux	SIGNOR-105206
O14595	P84022	1	dephosphorylation	up-regulates activity	0.424	Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3\|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity	SIGNOR-248293
P27361	P04049	1	phosphorylation	down-regulates activity	0.637	Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. \| Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.\|FLAG-Raf-1 phosphorylated by activated ERK2	SIGNOR-143688
Q05513	P47712	1	phosphorylation	up-regulates activity	0.327	To further evaluate cPLA2 as a candidate substrate for PKCζ, we developed a custom antibody recognizing the cPLA2 T376 phosphorylation site. Specificity was validated in both serum starved/stimulated samples	SIGNOR-277518
P20908	P13497	0	cleavage	up-regulates activity	0.623	BMP-1 Can Efficiently Cleave Pro-α1(V) N-propeptides and Pro-α2(V) C-propeptides and Less Efficiently Cleave Pro-α1(V) C-propeptides in Vitro.NH2-terminal sequencing of an ∼35-kDa band in the BMP-1-treated material (N-α1(V), Fig. 3 B,lanes 2 and 3) showed it to correspond to the NH2-terminal portion of the pro-α1(V) N-propeptide previously shown to be cleaved in pro-α1(V)3 homotrimers by BMP-1 (39), whereas NH2-terminal sequencing of an ∼38-kDa band (C-α1(V)BMP-1, Fig. 3 B,lanes 2 and 3) showed it to correspond to pro-α1(V) C-propeptides cleaved between Asp-1594 and Asp-1595.	SIGNOR-256344
Q13347	P37173	2	binding	up-regulates	0.324	Another receptor-associated protein is trip-1, which interacts with and is phosphorylated by tbrii and contains five wd-40 repeats. The association of wd-40 repeat proteins may then allow them to play a role in signaling by the serine/threonine kinase receptors.	SIGNOR-60700
P61006	O43318	0	phosphorylation	up-regulates activity	0.252	In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. \|Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.\|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease	SIGNOR-260266
O15519	Q16539	0	phosphorylation	up-regulates	0.373	Here we demonstrate that m. tuberculosis?induced Tnf triggered reactive oxygen species?dependent Activation of ask1 and the tyrosine kinase c-abl (a000161) in mouse macrophages and that flips was phosphorylated on tyr211 and ser4 by c-abl and p38, respectively.	SIGNOR-187001
Q9NR28	O15392	2	binding	down-regulates	0.569	Diablo seem to function as a general iaps neutralizer by binding to these protein. Diablo promotes casp9 activation by binding to inhibitor of apoptosis proteins, iaps, and removing their inhibitory activity. mitochondrial survivin associated with smac/diablo, delaying its release.	SIGNOR-80212
Q8WV28	P43405	0	phosphorylation	up-regulates	0.806	The phosphorylation of multiple tyrosine residues not only amplifies plcgamma-mediated signaling but also supports 'cis'-mediated interaction between distinct signaling effectors within a large molecular complex.	SIGNOR-96044
Q6PIL6	Q9NZV8	1	relocalization	up-regulates activity	0.773	KChIP4 increased the current amplitude of Kv4.2, decelerated the inactivation, and accelerated the recovery from inactivation of Kv4.2. KChIP.is known to promote the translocation of Kv4.2 from the endoplasmic reticulum or Golgi to the cell surface	SIGNOR-269004
Q92786	P54646	0	phosphorylation	down-regulates quantity by destabilization	0.2	Furthermore, the Ser79 phosphorylation of PROX1 by AMPK enhances the recruitment of CUL4-DDB1 ubiquitin ligase to promote PROX1 degradation.	SIGNOR-277608
P42768	P60953	2	binding	up-regulates activity	0.957	Cdc42 can induce Arp2/3-mediated filopodia formation through the activation of WASp (Wiskott-Aldrich syndrome proteins) and neuronal N-WASp (Rohatgi et al., 1999). Similarly, Rac1-enhanced lamellipodia formation is related to Arp2/3 activation by the WAVE (WASP-family verprolin-homologous) complex	SIGNOR-261869
O14965	P06730	1	phosphorylation	up-regulates activity	0.278	In this study, we demonstrated for the first time that AURKA can phosphorylate and activate EIF4E.	SIGNOR-279495
Q96NX5	O43432	1	phosphorylation	up-regulates	0.2	Here we report that activity-dependent translational initiation in cultured rat hippocampal neurons is enhanced by camki-mediated phosphorylation of ser1156 in eukaryotic initiation factor eif4gii (4gii).	SIGNOR-197149
P04637	O96017	0	phosphorylation	up-regulates quantity by stabilization	0.791	Chk1/chk2 and atm/atr also phosphorylate the effector p53, increasing its stability.We Have demonstrated that the human homologs of the checkpoint kinases, chk1 and chk2/hcds1, phosphorylate at least three dna damage-inducible phosphorylation sites in p53.	SIGNOR-74831
P49760	P31749	0	phosphorylation	up-regulates	0.39	Akt directly binds to and phosphorylates clk2 on serine 34 and threonine 127, in vitro and in vivo.Our results suggest that akt activation controls cell survival to ionizing radiation by phosphorylating clk2, revealing an important regulatory mechanism required for promoting cell surviva	SIGNOR-167340
P63092	O14842	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256799
Q07960	P61586	1	gtpase-activating protein	down-regulates activity	0.864	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-260458
P06239	P20138	1	phosphorylation	up-regulates	0.271	Human cd33 has two tyrosine residues in its cytoplasmic domain (y340 and y358). When phosphorylated, these tyrosines could function as docking sites for the phosphatases, shp-1 and/or shp-2, enabling cd33 to function as an inhibitory receptor. Lck is effective at phosphorylating y340	SIGNOR-78960
P28482	P19634	1	phosphorylation	up-regulates	0.669	We have demonstrated that the map kinases extracellular signal-regulated kinases 1 and 2 (erk1/2) are implicated in growth factor activation of nhe1. / our results suggest that amino acids ser770 and ser771 mediate erk-dependent activation of the na+/h+ exchanger in vivo.	SIGNOR-151925
P0DP24	P00533	0	phosphorylation	down-regulates	0.345	Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.	SIGNOR-266319
Q9P2B4	Q14247	2	binding	up-regulates activity	0.357	CTTNBP2NL interacts with cortactin and targets cortactin to stress fibers.	SIGNOR-261695
P49683	P09471	2	binding	up-regulates activity	0.306	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-256973
O96017	Q96GD4	1	phosphorylation	up-regulates activity	0.324	Because Chk1 and Chk2 can share substrates ( ), we investigated whether Chk2 phosphorylates Aurora B-B-serine 331 in nocodazole.\|In addition, Chk2 promotes proper chromosome alignment through Aurora B-B-serine 331 phosphorylation.	SIGNOR-278906
P24666	P14618	1	dephosphorylation	up-regulates activity	0.279	Indeed, it is evident that LMW-PTP, hydrolyzing phosphotyrosine residues, contributes to maintain PKM2 in its active form.\|We speculate that this effect is in large part due to LMW-PTP inhibition, which leads a fast PKM2 phosphorylation and inactivation.\|we demonstrate that in melanoma cells the overexpression of LMW-PTP is functional to maintain PKM2 in its dephosphorylate status – the tetrameric, “full active” form - which is retained in the cytoplasm	SIGNOR-277134
P17612	Q92837	1	phosphorylation	down-regulates	0.2	Phosphorylation of ser188 by pka inhibited the ability of frat1 to activate beta-catenin-dependent transcription.	SIGNOR-149689
P01111	P42336	2	binding	up-regulates activity	0.844	Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner./lysine residue 227 is essential for the interaction of ras with pi3k	SIGNOR-175222
Q93045	P53779	0	phosphorylation	down-regulates	0.444	We demonstrate that purified scg10 can be phosphorylated by two subclasses of mitogen-activated protein (map) kinases, c-jun n-terminal/stress-activated protein kinase (jnk/sapk) and p38 map kinase;jnk3/sapkbeta phosphorylation occurs at ser-62 and ser-73, residues that result in reduced microtubule-destabilizing activity for scg10.	SIGNOR-112114
Q9Y6X2	P40763	1	sumoylation	down-regulates	0.731	Stat3 mediated signaling pathways can be inhibited by pias3 (protein inhibitor of activated stat3), which was recently found to regulate protein stability and function by its sumo (small-ubiquitin like modifiers) ligase activity in promoting sumoylation of important nuclear proteins.	SIGNOR-124723
P28482	Q15746	1	phosphorylation	up-regulates activity	0.478	Inhibition of ERK2 impaired phosphorylation of MLCK and insulin stimulated glucose uptake.\|These findings suggest that ERK2 activates MLCK which then mediates the phosphorylation of RLC of MyoIIA.	SIGNOR-279226
Q66LE6	P56211	2	binding	down-regulates activity	0.694	We identified cyclic adenosine monophosphateregulated phosphoprotein 19 (Arpp19) and -Endosulfine as two substrates of Gwl that, when phosphorylated by this kinase, associate with and inhibit PP2A, thus promoting mitotic entry.	SIGNOR-243731
O95837	O43603	2	binding	up-regulates activity	0.311	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-257136
P67775	P31749	1	dephosphorylation	down-regulates activity	0.893	Protein phosphatase 2A negatively regulates insulin's metabolic signaling pathway by inhibiting Akt (protein kinase B) activity in 3T3-L1 adipocytes	SIGNOR-252614
Q08881	Q08881	2	phosphorylation	up-regulates activity	0.2	In this study, we present evidence for another mode of regulation for itk, the autophosphorylation of tyr-180 in the src homology 3 (sh3) domain.	SIGNOR-103170
Q9NS75	P19086	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256889
Q8N726	Q9HCX3	0	transcriptional regulation	down-regulates quantity by repression	0.302	Finally, we show that ZNF304 also directs transcriptional silencing of INK4-ARF in human embryonic stem cells.	SIGNOR-266098
P98082	Q05655	0	phosphorylation	down-regulates	0.296	Mutational analysis revealed that a dab2 ser(24) phosphorylation mutant (s24a) abrogated the inhibitory function of dab2.	SIGNOR-127198
Q14980	P11171	0	relocalization	up-regulates activity	0.533	These results indicate that 4.1 proteins recruit NuMA and dynein to the anaphase cell cortex through their conserved CTD (Figure 2I).	SIGNOR-266012
Q9HC98	O00141	1	phosphorylation	up-regulates activity	0.338	The present study is the first report of a protein kinase (NEK6) capable of phosphorylating the hydrophobic motif of SGK1, although our data suggest that NEK6 may not mediate this reaction in cells. Nevertheless, the phosphorylation of the hydrophobic motif of SGK1in vitro, coupled with the phosphorylation of the T-loop with PDK1, may be a useful way of generating fully active wild type SGK1. Ser377 and Ser422of SGK1, and the CDK7 T-loop peptide, which are phosphorylated by NEK6.	SIGNOR-250297
P18850	P18850	2	binding	up-regulates activity	0.2	E4BP4, ATF-6, OASIS, and XBP-1 all formed strong homodimeric associations on the array Transcription factor dimerization can increase the selectivity of protein-DNA interactions and generate a large amount of DNA binding diversity from a relatively small number of proteins	SIGNOR-224202
Q8NG66	O14757	0	phosphorylation	up-regulates	0.264	We demonstrate that chk1 (checkpoint kinase 1) directly activates nek11 by phosphorylating it on ser 273	SIGNOR-187863
P57058	O43736	1	phosphorylation	up-regulates activity	0.2	ITM2A is phosphorylated at T35 and the phosphorylation status of ITM2A contributes to breast cancer proliferation. Moreover, we found that ITM2A was phosphorylated at T35 by HUNK, a serine/threonine kinase significantly correlated with human breast cancer overall survival and HER2-induced mammary tumorigenesis.	SIGNOR-273640
Q9Y4K3	Q15750	2	binding	up-regulates activity	0.865	The irak1/traf6 complex can also activate jnk and p38 signalling through assembly of a catalytically active tab2-tab3-tak1 complex.	SIGNOR-205455
Q9Y5I2	O60330	2	binding	up-regulates activity	0.2	The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.	SIGNOR-265698
P29323	P29323	2	phosphorylation	up-regulates activity	0.2	Our results demonstrate that autophosphorylation tyrosine 611 in the juxtamembrane region of chicken EphB2 is critical for the association of the Src SH2 domain.	SIGNOR-251124
P67775	P36507	1	dephosphorylation	down-regulates	0.493	In particular, p38 mapk activity stimulates the physical association between ppa2 and mkk1/2- erk1/2 complex, leading to mkk1/2 dephosphorilation by pp2a.	SIGNOR-166652
P56750	Q8TBB1	0	ubiquitination	down-regulates quantity by destabilization	0.294	We used the Ligand of Numb protein X (LNX) family of E3s, a group of PDZ domain-containing RING-type E3 ubiquitin ligases, to demonstrate the feasibility of this strategy. Many potential substrates of LNX E3s were identified. Eight of the nine selected candidates were ubiquitinated in vitro, and two novel endogenous substrates, PDZ-binding kinase (PBK) and breakpoint cluster region protein (BCR), were confirmed in vivo.	SIGNOR-272900
P51681	P13236	2	binding	up-regulates activity	0.862	The investigators showed that myoblasts constitutively express receptors for CCL2 (CCR2), CCL3 (CCR1 and CCR5), and CCL4 (CCR5), and that stimulation with either CCL2 or CCL4 was sufficient to promote myoblast proliferation.	SIGNOR-255116
Q99814	O94953	1	transcriptional regulation	up-regulates quantity by expression	0.2	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271584
Q92785	P11474	2	binding	down-regulates activity	0.2	DPF2 directly bound to ERRalpha and suppressed the transactivation function of nuclear receptors such as androgen receptor. DPF2 was recruited to ERR target gene promoters in myoblast cells, and knockdown of DPF2 derepressed the level of mRNA expressed by target genes of ERRalpha. These results show that DPF2 acts as a nuclear receptor-selective co-repressor for ERRalpha by associating with both acetylated histone H3 and HDAC1.	SIGNOR-239539
Q13976	P26678	1	phosphorylation	up-regulates activity	0.409	Phosphorylation of PLB by PKA or cGKI at Ser 16 relieves the inhibition of SERCA2a and results in increased contractility through enhanced Ca 2+ i reuptake into the SR.	SIGNOR-279269
Q8TDI7	Q96QU1	2	binding	up-regulates activity	0.436	Although several studies show that the tip links, composed of PCDH15 and CDH23, are required for normal mechanotransduction, it is unclear how they are coupled to the transduction machinery. Likewise, it has been demonstrated that the transmembrane channel-like proteins TMC1 and TMC2 are required for mechanosensitive responses in hair cells, but how they interact with other components of the mechanotransduction complex is not known. Here, we show that TMC1 and TMC2 can interact with PCDH15, thereby establishing a critical connection between the tip link and these putative components of the mechanotransduction channel in hair cells.	SIGNOR-262583
O76050	P78504	1	ubiquitination	down-regulates quantity by destabilization	0.707	We find that NEDD4 targets an RNA-binding protein, NANOS2, in spermatogonia to destabilize it, leading to cell differentiation.\|Jagged1 is also regulated by the E3 ligase Neuralized-like1 (Neurl1), which induces the monoubiquitination of membrane tethered Jagged1 in the C-terminal region.	SIGNOR-278772
P12931	P09327	1	phosphorylation	up-regulates activity	0.363	These data suggest that phosphorylation of villin by c-src is involved in the actin cytoskeleton remodeling necessary for cell migration.To further investigate the role of tyrosine phosphorylated villin in cell migration, we used phosphorylation site mutants (tyrosine to phenylalanine or tyrosine to glutamic acid) in HeLa cells. We determined that tyrosine phosphorylation at residues 60, 81, and 256 of human villin played an essential role in cell migration as well as in the reorganization of the actin cytoskeleton	SIGNOR-247441
P31323	P17612	2	binding	down-regulates activity	0.881	Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets	SIGNOR-258754
P54274	O95271	0	ADP-ribosylation	down-regulates activity	0.803	Tankyrase 1 ADP-ribosylates TRF1, inhibiting its binding to telomeric DNA.	SIGNOR-263377
Q5VU43	P10644	2	binding	up-regulates	0.315	Mmgl acts as a dual-specific akap by anchoring pka regulatory isoforms r1a and r2a.	SIGNOR-173769
Q96GD4	O95229	1	phosphorylation	up-regulates activity	0.651	Zwint-1 is a novel Aurora B substrate required for the assembly of a dynein-binding platform on kinetochores\|During prometaphase, AurB phosphorylation of zwint-1 is required for recruitment of ZW10-, pT89 dynein-, and RZZ-dependent proteins to kinetochores. This is defective after AurB inhibition or after expression of the triple-A zwint-1 mutant. Triple-E mutant zwint-1 mimics phospho–zwint-1 in RZZ recruitment, even after AurB inhibition	SIGNOR-265010
Q13263	Q00987	2	binding	up-regulates activity	0.598	we present evidence that MDM2 interacts with the nuclear corepressor KAP1. MDM2 interaction with nuclear corepressor KAP1 contributes to p53 inactivation.	SIGNOR-240405
P06493	Q02952	1	phosphorylation	up-regulates activity	0.322	Mass spectrometry, molecular, and cellular approaches show that CDK1/Cyclin B1 phosphorylates Gravin on threonine 766 to prime the recruitment of the polo-like kinase Plk1 at defined phases of mitosis.	SIGNOR-271839
P50148	Q99527	2	binding	up-regulates	0.2	However, grpr preferentially couples to galfaq proteins.	SIGNOR-195320
P09471	P28566	2	binding	up-regulates activity	0.378	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-256984
O15552	P63092	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256803
Q04760	P54756	0	phosphorylation	up-regulates activity	0.2	We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).	SIGNOR-276183
O75084	P56703	2	binding	up-regulates activity	0.743	These experiments suggest that activation of the Wnt/β-catenin pathway by Wnt3 is mediated in part through FZD7 in HCC cells.	SIGNOR-280437
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
P21802	P11487	2	binding	up-regulates	0.767	Using fgf 1 as an internal standard we have determined the relative activity of all the other members of the fgf family. These data should serve as a biochemical foundation for determining developmental, physiological, and pathophysiological processes that involve fgf signaling pathways	SIGNOR-42374
Q9UL15	P0DMV8	2	binding	down-regulates activity	0.753	Here, we show that BAG5, a BAG domain-containing family member, interacts with both Hsp70 and parkin with deleterious functional consequences. Through these interactions, BAG5 inhibits Hsp70 chaperone activity and parkin E3 ubiquitin ligase activity; Thus, BAG5 interacts with Hsp70 in vitro and in vivo, and substitution of select residues within the BAG domains is sufficient to abolish this interaction.	SIGNOR-261196
Q14693	P12931	0	phosphorylation	up-regulates activity	0.2	Obesity-associated microenvironmental factors and other Src-activating growth factors, including the epidermal growth factor, activate Src and promote Src-mediated lipin-1 phosphorylation on Tyr398, Tyr413 and Tyr795 residues. The tyrosine phosphorylation of lipin-1 markedly increases its PAP activity, accelerating the synthesis of glycerophospholipids and triglyceride.	SIGNOR-277291
Q13535	Q9UIF7	2	binding	up-regulates	0.25	Binding of myh directly participates in atr and topbp1 activation in dna damage signaling, leading to apoptosis.	SIGNOR-173966
P31751	Q15672	1	phosphorylation	up-regulates activity	0.398	AKT2 phosphorylates Twist1 at S42 to enhance Twist1 mediated E-cadherin suppression.	SIGNOR-279137
Q13164	Q13164	2	phosphorylation	up-regulates activity	0.2	Activated ERK5 undergoes autophosphorylation on its C-terminal half, necessary for maximal activation of ERK5 transcriptional activation. The Ser731 and Thr733 sites were previously shown to be ERK5 autophosphorylation sites in vitro and also in ERK5-overexpressing cells.Our data coincide with a recent study examining whole protein phosphorylation in HeLa cells arrested in G1 and mitotic phases [37] reported that Ser731 and Thr733, as well as Ser720, are phosphorylated in ERK5 during mitosis. We also identified two unreported ERK5 phosphorylation sites, Ser567 and Ser803.	SIGNOR-259826
P14138	P23276	0	cleavage	up-regulates activity	0.676	These data demonstrate that the Kell blood group protein is a proteolytic enzyme that processes big ET-3, generating ET-3, a potent bioactive peptide with multiple biological roles.	SIGNOR-256354
Q9Y4H2	P08069	0	phosphorylation	up-regulates	0.802	Our results reveal that igf-1 receptors promote beta-cell development and survival through the irs-2 signalling pathway.	SIGNOR-70477
O76039	O76039	2	phosphorylation	up-regulates activity	0.2	Furthermore, we show that CDKL5 can self-associate and mediate the phosphorylation of its own TEY (Thr-Glu-Tyr) motif.	SIGNOR-262289
Q8NFU7	O94813	1	transcriptional regulation	up-regulates quantity by expression	0.2	Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9.	SIGNOR-259093
Q92974	Q14012	0	phosphorylation	up-regulates activity	0.389	In this study, we found that CaMKI phosphorylated GEF-H1 at Thr103, which is located close to the C1 domain.	SIGNOR-279359

Q08211

Q9BRS8

2

binding

up-regulates activity

0.41

La ribonucleoprotein domain family member 6 (LARP6) is the protein that binds 5' SL with high affinity and specificity and coordinates their translation. Here we show that RNA helicase A (RHA) is tethered to the 5' SL of collagen mRNAs by interaction with the C-terminal domain of LARP6.

SIGNOR-273500

Q9BYP7

P55011

1

phosphorylation

up-regulates activity

0.525

We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs

SIGNOR-264625

Q13188

Q9UL54

0

phosphorylation

up-regulates

0.274

In addition, the thousand-and-one (tao) amino acids kinase or taok13 has been shown to directly phosphorylate and activate hpo or mst1/2.

SIGNOR-201327

P06241

Q16620

2

binding

up-regulates

0.381

All these data suggest the involvement of fyn in the neurotrophin signal transduction pathways downstream of trkb. We investigated whether fyn is involved in the trk-dependent signal transduction pathways of neurotrophin. The fyn-src homology domain 2 (sh2) was observed to associate in vitro with the intracellular domain of trkb (icd-trkb).

SIGNOR-58424

O14757

O15151

1

phosphorylation

down-regulates activity

0.52

MDMX is a direct substrate for Chk1 and Chk2 in vitro. Phosphorylation of MDMX leads to increased binding to MDM2 and more efficient ubiquitination, providing an explanation for the enhanced degradation of MDMX after DNA damage. | Western blot showed that Chk1 modified S342 and S367, but with strong preference for S342.

SIGNOR-250770

Q92538

P68400

0

phosphorylation

down-regulates quantity by destabilization

0.2

We show that, in mitosis, GBF1 is phosphorylated on Ser292 and Ser297 by casein kinase-2 allowing recognition by the F-box protein βTrCP. GBF1 interaction with βTrCP recruits GBF1 to the SCFβTrCP ubiquitin ligase complex, triggering its degradation.

SIGNOR-277398

Q9BZL4

P54646

0

phosphorylation

down-regulates

0.259

Ampk-induced phosphorylation is necessary for ppp1r12c interaction with 14-3-3 and phosphorylation of myosin regulatory light chain. Both ampk activity and ppp1r12c phosphorylation are increased in mitotic cells and are important for mitosis completion. The interaction between ppp1r12c and 14-3-3_ may inactivate the ppp1r12c-containing phosphatase complex in vivo.

SIGNOR-195148

P05412

P98066

1

transcriptional regulation

up-regulates quantity by expression

0.308

Tumor necrosis factor (TNF)-stimulated gene 6 (TSG-6) encodes a protein expressed during inflammation. We have previously shown that transcription factors of the NF-IL6 and AP-1 families cooperatively modulate activation of the TSG-6 gene by TNF or interleukin 1 (IL-1) through a promoter region that contains an NF-IL6 site (-106 to -114) and an AP-1 element

SIGNOR-254052

P78352

Q9HCJ2

2

binding

up-regulates activity

0.365

A possible function for the NGL–PSD-95 interaction is to couple trans-synaptic adhesion events to the recruitment of PSD-95 and other PSD-95-associated postsynaptic proteins. PSD-95 and liprin-α may be key synaptic scaffolding proteins that couple trans-synaptic adhesions to the assembly of synaptic proteins/vesicles

SIGNOR-264050

P11473

O60315

0

transcriptional regulation

up-regulates quantity by expression

0.2

ZEB, a Krüppel-type transcription factor known to repress the transcription of several genes, binds to two sites within the VDR promoter and activates the transcription of this receptor in a cell-specific manner. Transfection of ZEB into SW620 colon carcinoma cells results in an up-regulation of the expression of endogenous VDR, confirming the role of ZEB in the transcriptional activation of the VDR gene.

SIGNOR-268954

P08754

P30556

2

binding

up-regulates activity

0.25

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256881

Q13144

P68400

0

phosphorylation

up-regulates activity

0.386

Two conserved sites (Ser712/713) are phosphorylated by casein kinase 2. They lie at the extreme C-terminus and are required for the interaction of eIF2Bepsilon with its substrate, eIF2, in vivo and for eIF2B activity in vitro.

SIGNOR-250859

P0C2W1

O15350

2

binding

down-regulates quantity by destabilization

0.597

The F-box protein FBXO45 promotes the proteasome-dependent degradation of p73.Importantly, SCFFBXO45 ubiquitylates p73 both in vivo and in vitro. Expression of Cul1 dominant negative mutant, but not Cul2, Cul3, Cul4 and Cul5 dominant negative mutants, increased p73 levels (Figure 1c) to an extent similar to that observed in the ts41 cell line at not permissive temperature, suggesting that a Cul1-associated activity is required for p73 protein stability.

SIGNOR-271876

P31269

O00470

2

binding

up-regulates activity

0.62

We now show that the Hoxa-9 protein physically interacts with Meis1 proteins. Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.

SIGNOR-241162

Q12888

P06493

0

phosphorylation

down-regulates activity

0.599

Nuclear import of 53BP1 is required for proper localization of 53BP1 and maintenance of genome integrity. 53BP1 has a classical bipartite nuclear localization signal (NLS) of sequence 1666-GKRKLITSEEERSPAKRGRKS-1686. Ser1678 within the 53BP1 NLS can be phosphorylated by CDK1/cyclin B, and a phosphomimetic substitution of Ser1678 with aspartate has been shown to negatively regulate nuclear import of 53BP1.

SIGNOR-264412

P63000

P36897

0

null

up-regulates activity

0.28

Thus, TGF-_1 rapidly stimulates activity of both RhoA and Rac1 and this activation requires ALK5/T_RI kinase activity.

SIGNOR-227496

P17931

P42684

0

phosphorylation

up-regulates

0.2

The sh (src homology)3 domains of c-abl/arg bind to a p(80)gppsgp motif of gal3, and tyr79 and tyr118 are the major tyrosine phosphorylation sites. A consequence of this interaction and phosphorylation is the significant impairment of chaperone-mediated autophagy of gal3.

SIGNOR-163747

Q13464

Q14457

1

phosphorylation

up-regulates activity

0.415

Beclin1 is phosphorylated by ROCK1 at T119.

SIGNOR-278198

P11387

P06493

0

phosphorylation

up-regulates activity

0.349

In vitro kinase assays demonstrated that Ser(10) can be phosphorylated by casein kinase II, Ser(21) can be phosphorylated by protein kinase Calpha, and Ser(112) and Ser(394) can be phosphorylated by Cdk1.Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells.

SIGNOR-276157

Q9UHD2

A7MCY6

0

relocalization

up-regulates activity

0.603

TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation

SIGNOR-272469

Q04724

Q9UJU2

2

binding

down-regulates activity

0.689

Our data shows that Groucho/TLE repression requires two sites of interaction in LEF-1 and that a central, conserved amino acid sequence within the primary region (F S/T/P/xx y I/L/V) is critical.

SIGNOR-260109

Q14934

Q08209

0

dephosphorylation

up-regulates

0.566

Calcineurin directly dephosphorylates nfat resulting in the nuclear import of nfat.

SIGNOR-176379

Q16611

P99999

1

relocalization

up-regulates

0.566

Allosteric activation of bak induces its intramembranous oligomerization into a proposed pore for cytochrome c efflux

SIGNOR-105206

O14595

P84022

1

dephosphorylation

up-regulates activity

0.424

Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity

SIGNOR-248293

P27361

P04049

1

phosphorylation

down-regulates activity

0.637

Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2

SIGNOR-143688

Q05513

P47712

1

phosphorylation

up-regulates activity

0.327

To further evaluate cPLA2 as a candidate substrate for PKCζ, we developed a custom antibody recognizing the cPLA2 T376 phosphorylation site. Specificity was validated in both serum starved/stimulated samples

SIGNOR-277518

P20908

P13497

0

cleavage

up-regulates activity

0.623

BMP-1 Can Efficiently Cleave Pro-α1(V) N-propeptides and Pro-α2(V) C-propeptides and Less Efficiently Cleave Pro-α1(V) C-propeptides in Vitro.NH2-terminal sequencing of an ∼35-kDa band in the BMP-1-treated material (N-α1(V), Fig. 3 B,lanes 2 and 3) showed it to correspond to the NH2-terminal portion of the pro-α1(V) N-propeptide previously shown to be cleaved in pro-α1(V)3 homotrimers by BMP-1 (39), whereas NH2-terminal sequencing of an ∼38-kDa band (C-α1(V)BMP-1, Fig. 3 B,lanes 2 and 3) showed it to correspond to pro-α1(V) C-propeptides cleaved between Asp-1594 and Asp-1595.

SIGNOR-256344

Q13347

P37173

2

binding

up-regulates

0.324

Another receptor-associated protein is trip-1, which interacts with and is phosphorylated by tbrii and contains five wd-40 repeats. The association of wd-40 repeat proteins may then allow them to play a role in signaling by the serine/threonine kinase receptors.

SIGNOR-60700

P61006

O43318

0

phosphorylation

up-regulates activity

0.252

In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. |Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease

SIGNOR-260266

O15519

Q16539

0

phosphorylation

up-regulates

0.373

Here we demonstrate that m. tuberculosis?induced Tnf triggered reactive oxygen species?dependent Activation of ask1 and the tyrosine kinase c-abl (a000161) in mouse macrophages and that flips was phosphorylated on tyr211 and ser4 by c-abl and p38, respectively.

SIGNOR-187001

Q9NR28

O15392

2

binding

down-regulates

0.569

Diablo seem to function as a general iaps neutralizer by binding to these protein. Diablo promotes casp9 activation by binding to inhibitor of apoptosis proteins, iaps, and removing their inhibitory activity. mitochondrial survivin associated with smac/diablo, delaying its release.

SIGNOR-80212

Q8WV28

P43405

0

phosphorylation

up-regulates

0.806

The phosphorylation of multiple tyrosine residues not only amplifies plcgamma-mediated signaling but also supports 'cis'-mediated interaction between distinct signaling effectors within a large molecular complex.

SIGNOR-96044

Q6PIL6

Q9NZV8

1

relocalization

up-regulates activity

0.773

KChIP4 increased the current amplitude of Kv4.2, decelerated the inactivation, and accelerated the recovery from inactivation of Kv4.2. KChIP.is known to promote the translocation of Kv4.2 from the endoplasmic reticulum or Golgi to the cell surface

SIGNOR-269004

Q92786

P54646

0

phosphorylation

down-regulates quantity by destabilization

0.2

Furthermore, the Ser79 phosphorylation of PROX1 by AMPK enhances the recruitment of CUL4-DDB1 ubiquitin ligase to promote PROX1 degradation.

SIGNOR-277608

P42768

P60953

2

binding

up-regulates activity

0.957

Cdc42 can induce Arp2/3-mediated filopodia formation through the activation of WASp (Wiskott-Aldrich syndrome proteins) and neuronal N-WASp (Rohatgi et al., 1999). Similarly, Rac1-enhanced lamellipodia formation is related to Arp2/3 activation by the WAVE (WASP-family verprolin-homologous) complex

SIGNOR-261869

O14965

P06730

1

phosphorylation

up-regulates activity

0.278

In this study, we demonstrated for the first time that AURKA can phosphorylate and activate EIF4E.

SIGNOR-279495

Q96NX5

O43432

1

phosphorylation

up-regulates

0.2

Here we report that activity-dependent translational initiation in cultured rat hippocampal neurons is enhanced by camki-mediated phosphorylation of ser1156 in eukaryotic initiation factor eif4gii (4gii).

SIGNOR-197149

P04637

O96017

0

phosphorylation

up-regulates quantity by stabilization

0.791

Chk1/chk2 and atm/atr also phosphorylate the effector p53, increasing its stability.We Have demonstrated that the human homologs of the checkpoint kinases, chk1 and chk2/hcds1, phosphorylate at least three dna damage-inducible phosphorylation sites in p53.

SIGNOR-74831

P49760

P31749

0

phosphorylation

up-regulates

0.39

Akt directly binds to and phosphorylates clk2 on serine 34 and threonine 127, in vitro and in vivo.Our results suggest that akt activation controls cell survival to ionizing radiation by phosphorylating clk2, revealing an important regulatory mechanism required for promoting cell surviva

SIGNOR-167340

P63092

O14842

2

binding

up-regulates activity

0.2

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256799

Q07960

P61586

1

gtpase-activating protein

down-regulates activity

0.864

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-260458

P06239

P20138

1

phosphorylation

up-regulates

0.271

Human cd33 has two tyrosine residues in its cytoplasmic domain (y340 and y358). When phosphorylated, these tyrosines could function as docking sites for the phosphatases, shp-1 and/or shp-2, enabling cd33 to function as an inhibitory receptor. Lck is effective at phosphorylating y340

SIGNOR-78960

P28482

P19634

1

phosphorylation

up-regulates

0.669

We have demonstrated that the map kinases extracellular signal-regulated kinases 1 and 2 (erk1/2) are implicated in growth factor activation of nhe1. / our results suggest that amino acids ser770 and ser771 mediate erk-dependent activation of the na+/h+ exchanger in vivo.

SIGNOR-151925

P0DP24

P00533

0

phosphorylation

down-regulates

0.345

Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.

SIGNOR-266319

Q9P2B4

Q14247

2

binding

up-regulates activity

0.357

CTTNBP2NL interacts with cortactin and targets cortactin to stress fibers.

SIGNOR-261695

P49683

P09471

2

binding

up-regulates activity

0.306

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-256973

O96017

Q96GD4

1

phosphorylation

up-regulates activity

0.324

Because Chk1 and Chk2 can share substrates ( ), we investigated whether Chk2 phosphorylates Aurora B-B-serine 331 in nocodazole.|In addition, Chk2 promotes proper chromosome alignment through Aurora B-B-serine 331 phosphorylation.

SIGNOR-278906

P24666

P14618

1

dephosphorylation

up-regulates activity

0.279

Indeed, it is evident that LMW-PTP, hydrolyzing phosphotyrosine residues, contributes to maintain PKM2 in its active form.|We speculate that this effect is in large part due to LMW-PTP inhibition, which leads a fast PKM2 phosphorylation and inactivation.|we demonstrate that in melanoma cells the overexpression of LMW-PTP is functional to maintain PKM2 in its dephosphorylate status – the tetrameric, “full active” form - which is retained in the cytoplasm

SIGNOR-277134

P17612

Q92837

1

phosphorylation

down-regulates

0.2

Phosphorylation of ser188 by pka inhibited the ability of frat1 to activate beta-catenin-dependent transcription.

SIGNOR-149689

P01111

P42336

2

binding

up-regulates activity

0.844

Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner./lysine residue 227 is essential for the interaction of ras with pi3k

SIGNOR-175222

Q93045

P53779

0

phosphorylation

down-regulates

0.444

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

SIGNOR-112114

Q9Y6X2

P40763

1

sumoylation

down-regulates

0.731

Stat3 mediated signaling pathways can be inhibited by pias3 (protein inhibitor of activated stat3), which was recently found to regulate protein stability and function by its sumo (small-ubiquitin like modifiers) ligase activity in promoting sumoylation of important nuclear proteins.

SIGNOR-124723

P28482

Q15746

1

phosphorylation

up-regulates activity

0.478

Inhibition of ERK2 impaired phosphorylation of MLCK and insulin stimulated glucose uptake.|These findings suggest that ERK2 activates MLCK which then mediates the phosphorylation of RLC of MyoIIA.

SIGNOR-279226

Q66LE6

P56211

2

binding

down-regulates activity

0.694

We identified cyclic adenosine monophosphateregulated phosphoprotein 19 (Arpp19) and -Endosulfine as two substrates of Gwl that, when phosphorylated by this kinase, associate with and inhibit PP2A, thus promoting mitotic entry.

SIGNOR-243731

O95837

O43603

2

binding

up-regulates activity

0.311

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-257136

P67775

P31749

1

dephosphorylation

down-regulates activity

0.893

Protein phosphatase 2A negatively regulates insulin's metabolic signaling pathway by inhibiting Akt (protein kinase B) activity in 3T3-L1 adipocytes

SIGNOR-252614

Q08881

2

phosphorylation

up-regulates activity

0.2

In this study, we present evidence for another mode of regulation for itk, the autophosphorylation of tyr-180 in the src homology 3 (sh3) domain.

SIGNOR-103170

Q9NS75

P19086

2

binding

up-regulates activity

0.2

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256889

Q8N726

Q9HCX3

0

transcriptional regulation

down-regulates quantity by repression

0.302

Finally, we show that ZNF304 also directs transcriptional silencing of INK4-ARF in human embryonic stem cells.

SIGNOR-266098

P98082

Q05655

0

phosphorylation

down-regulates

0.296

Mutational analysis revealed that a dab2 ser(24) phosphorylation mutant (s24a) abrogated the inhibitory function of dab2.

SIGNOR-127198

Q14980

P11171

0

relocalization

up-regulates activity

0.533

These results indicate that 4.1 proteins recruit NuMA and dynein to the anaphase cell cortex through their conserved CTD (Figure 2I).

SIGNOR-266012

Q9HC98

O00141

1

phosphorylation

up-regulates activity

0.338

The present study is the first report of a protein kinase (NEK6) capable of phosphorylating the hydrophobic motif of SGK1, although our data suggest that NEK6 may not mediate this reaction in cells. Nevertheless, the phosphorylation of the hydrophobic motif of SGK1in vitro, coupled with the phosphorylation of the T-loop with PDK1, may be a useful way of generating fully active wild type SGK1. Ser377 and Ser422of SGK1, and the CDK7 T-loop peptide, which are phosphorylated by NEK6.

SIGNOR-250297

P18850

2

binding

up-regulates activity

0.2

E4BP4, ATF-6, OASIS, and XBP-1 all formed strong homodimeric associations on the array Transcription factor dimerization can increase the selectivity of protein-DNA interactions and generate a large amount of DNA binding diversity from a relatively small number of proteins

SIGNOR-224202

Q8NG66

O14757

0

phosphorylation

up-regulates

0.264

We demonstrate that chk1 (checkpoint kinase 1) directly activates nek11 by phosphorylating it on ser 273

SIGNOR-187863

P57058

O43736

1

phosphorylation

up-regulates activity

0.2

ITM2A is phosphorylated at T35 and the phosphorylation status of ITM2A contributes to breast cancer proliferation. Moreover, we found that ITM2A was phosphorylated at T35 by HUNK, a serine/threonine kinase significantly correlated with human breast cancer overall survival and HER2-induced mammary tumorigenesis.

SIGNOR-273640

Q9Y4K3

Q15750

2

binding

up-regulates activity

0.865

The irak1/traf6 complex can also activate jnk and p38 signalling through assembly of a catalytically active tab2-tab3-tak1 complex.

SIGNOR-205455

Q9Y5I2

O60330

2

binding

up-regulates activity

0.2

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

SIGNOR-265698

P29323

2

phosphorylation

up-regulates activity

0.2

Our results demonstrate that autophosphorylation tyrosine 611 in the juxtamembrane region of chicken EphB2 is critical for the association of the Src SH2 domain.

SIGNOR-251124

P67775

P36507

1

dephosphorylation

down-regulates

0.493

In particular, p38 mapk activity stimulates the physical association between ppa2 and mkk1/2- erk1/2 complex, leading to mkk1/2 dephosphorilation by pp2a.

SIGNOR-166652

P56750

Q8TBB1

0

ubiquitination

down-regulates quantity by destabilization

0.294

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

SIGNOR-272900

P51681

P13236

2

binding

up-regulates activity

0.862

The investigators showed that myoblasts constitutively express receptors for CCL2 (CCR2), CCL3 (CCR1 and CCR5), and CCL4 (CCR5), and that stimulation with either CCL2 or CCL4 was sufficient to promote myoblast proliferation.

SIGNOR-255116

Q99814

O94953

1

transcriptional regulation

up-regulates quantity by expression

0.2

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271584

Q92785

P11474

2

binding

down-regulates activity

0.2

DPF2 directly bound to ERRalpha and suppressed the transactivation function of nuclear receptors such as androgen receptor. DPF2 was recruited to ERR target gene promoters in myoblast cells, and knockdown of DPF2 derepressed the level of mRNA expressed by target genes of ERRalpha. These results show that DPF2 acts as a nuclear receptor-selective co-repressor for ERRalpha by associating with both acetylated histone H3 and HDAC1.

SIGNOR-239539

Q13976

P26678

1

phosphorylation

up-regulates activity

0.409

Phosphorylation of PLB by PKA or cGKI at Ser 16 relieves the inhibition of SERCA2a and results in increased contractility through enhanced Ca 2+ i reuptake into the SR.

SIGNOR-279269

Q8TDI7

Q96QU1

2

binding

up-regulates activity

0.436

Although several studies show that the tip links, composed of PCDH15 and CDH23, are required for normal mechanotransduction, it is unclear how they are coupled to the transduction machinery. Likewise, it has been demonstrated that the transmembrane channel-like proteins TMC1 and TMC2 are required for mechanosensitive responses in hair cells, but how they interact with other components of the mechanotransduction complex is not known. Here, we show that TMC1 and TMC2 can interact with PCDH15, thereby establishing a critical connection between the tip link and these putative components of the mechanotransduction channel in hair cells.

SIGNOR-262583

O76050

P78504

1

ubiquitination

down-regulates quantity by destabilization

0.707

We find that NEDD4 targets an RNA-binding protein, NANOS2, in spermatogonia to destabilize it, leading to cell differentiation.|Jagged1 is also regulated by the E3 ligase Neuralized-like1 (Neurl1), which induces the monoubiquitination of membrane tethered Jagged1 in the C-terminal region.

SIGNOR-278772

P12931

P09327

1

phosphorylation

up-regulates activity

0.363

These data suggest that phosphorylation of villin by c-src is involved in the actin cytoskeleton remodeling necessary for cell migration.To further investigate the role of tyrosine phosphorylated villin in cell migration, we used phosphorylation site mutants (tyrosine to phenylalanine or tyrosine to glutamic acid) in HeLa cells. We determined that tyrosine phosphorylation at residues 60, 81, and 256 of human villin played an essential role in cell migration as well as in the reorganization of the actin cytoskeleton

SIGNOR-247441

P31323

P17612

2

binding

down-regulates activity

0.881

Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets

SIGNOR-258754

P54274

O95271

0

ADP-ribosylation

down-regulates activity

0.803

Tankyrase 1 ADP-ribosylates TRF1, inhibiting its binding to telomeric DNA.

SIGNOR-263377

Q5VU43

P10644

2

binding

up-regulates

0.315

Mmgl acts as a dual-specific akap by anchoring pka regulatory isoforms r1a and r2a.

SIGNOR-173769

Q96GD4

O95229

1

phosphorylation

up-regulates activity

0.651

Zwint-1 is a novel Aurora B substrate required for the assembly of a dynein-binding platform on kinetochores|During prometaphase, AurB phosphorylation of zwint-1 is required for recruitment of ZW10-, pT89 dynein-, and RZZ-dependent proteins to kinetochores. This is defective after AurB inhibition or after expression of the triple-A zwint-1 mutant. Triple-E mutant zwint-1 mimics phospho–zwint-1 in RZZ recruitment, even after AurB inhibition

SIGNOR-265010

Q13263

Q00987

2

binding

up-regulates activity

0.598

we present evidence that MDM2 interacts with the nuclear corepressor KAP1. MDM2 interaction with nuclear corepressor KAP1 contributes to p53 inactivation.

SIGNOR-240405

P06493

Q02952

1

phosphorylation

up-regulates activity

0.322

Mass spectrometry, molecular, and cellular approaches show that CDK1/Cyclin B1 phosphorylates Gravin on threonine 766 to prime the recruitment of the polo-like kinase Plk1 at defined phases of mitosis.

SIGNOR-271839

P50148

Q99527

2

binding

up-regulates

0.2

However, grpr preferentially couples to galfaq proteins.

SIGNOR-195320

P09471

P28566

2

binding

up-regulates activity

0.378

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-256984

O15552

P63092

2

binding

up-regulates activity

0.2

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256803

Q04760

P54756

0

phosphorylation

up-regulates activity

0.2

We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).

SIGNOR-276183

O75084

P56703

2

binding

up-regulates activity

0.743

These experiments suggest that activation of the Wnt/β-catenin pathway by Wnt3 is mediated in part through FZD7 in HCC cells.

SIGNOR-280437

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

P21802

P11487

2

binding

up-regulates

0.767

Using fgf 1 as an internal standard we have determined the relative activity of all the other members of the fgf family. These data should serve as a biochemical foundation for determining developmental, physiological, and pathophysiological processes that involve fgf signaling pathways

SIGNOR-42374

Q9UL15

P0DMV8

2

binding

down-regulates activity

0.753

Here, we show that BAG5, a BAG domain-containing family member, interacts with both Hsp70 and parkin with deleterious functional consequences. Through these interactions, BAG5 inhibits Hsp70 chaperone activity and parkin E3 ubiquitin ligase activity; Thus, BAG5 interacts with Hsp70 in vitro and in vivo, and substitution of select residues within the BAG domains is sufficient to abolish this interaction.

SIGNOR-261196

Q14693

P12931

0

phosphorylation

up-regulates activity

0.2

Obesity-associated microenvironmental factors and other Src-activating growth factors, including the epidermal growth factor, activate Src and promote Src-mediated lipin-1 phosphorylation on Tyr398, Tyr413 and Tyr795 residues. The tyrosine phosphorylation of lipin-1 markedly increases its PAP activity, accelerating the synthesis of glycerophospholipids and triglyceride.

SIGNOR-277291

Q13535

Q9UIF7

2

binding

up-regulates

0.25

Binding of myh directly participates in atr and topbp1 activation in dna damage signaling, leading to apoptosis.

SIGNOR-173966

P31751

Q15672

1

phosphorylation

up-regulates activity

0.398

AKT2 phosphorylates Twist1 at S42 to enhance Twist1 mediated E-cadherin suppression.

SIGNOR-279137

Q13164

2

phosphorylation

up-regulates activity

0.2

Activated ERK5 undergoes autophosphorylation on its C-terminal half, necessary for maximal activation of ERK5 transcriptional activation. The Ser731 and Thr733 sites were previously shown to be ERK5 autophosphorylation sites in vitro and also in ERK5-overexpressing cells.Our data coincide with a recent study examining whole protein phosphorylation in HeLa cells arrested in G1 and mitotic phases [37] reported that Ser731 and Thr733, as well as Ser720, are phosphorylated in ERK5 during mitosis. We also identified two unreported ERK5 phosphorylation sites, Ser567 and Ser803.

SIGNOR-259826

P14138

P23276

0

cleavage

up-regulates activity

0.676

These data demonstrate that the Kell blood group protein is a proteolytic enzyme that processes big ET-3, generating ET-3, a potent bioactive peptide with multiple biological roles.

SIGNOR-256354

Q9Y4H2

P08069

0

phosphorylation

up-regulates

0.802

Our results reveal that igf-1 receptors promote beta-cell development and survival through the irs-2 signalling pathway.

SIGNOR-70477

O76039

2

phosphorylation

up-regulates activity

0.2

Furthermore, we show that CDKL5 can self-associate and mediate the phosphorylation of its own TEY (Thr-Glu-Tyr) motif.

SIGNOR-262289

Q8NFU7

O94813

1

transcriptional regulation

up-regulates quantity by expression

0.2

Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9.

SIGNOR-259093

Q92974

Q14012

0

phosphorylation

up-regulates activity

0.389

In this study, we found that CaMKI phosphorylated GEF-H1 at Thr103, which is located close to the C1 domain.

SIGNOR-279359