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
O60674	P28482	0	phosphorylation	down-regulates	0.513	We hypothesize that phosphorylation of ser523 in jak2 by erks 1 and/or 2 or other as-yet-unidentified kinases acts in a negative feedback manner	SIGNOR-236331
Q9BUB5	P47712	1	phosphorylation	up-regulates activity	0.577	The results suggest that MNK1 or a closely related kinase is responsible for in vivo phosphorylation of cPLA2 on Ser-727.	SIGNOR-226633
Q99619	P60321	2	binding	down-regulates quantity by destabilization	0.2	We have identified SPRY domain-containing SOCS (suppressor of cytokine signaling) box protein 2 (SPSB2) as a novel negative regulator that recruits an E3 ubiquitin ligase complex to polyubiquitinate iNOS, resulting in its proteasomal degradation. A cell-free ubiquitination assay was established to demonstrate SPSB2-dependent ubiquitination of iNOS. LPS/IFN-γ–stimulated macrophage lysates from Spsb2−/− mice were used as a source of iNOS and incubated with ubiquitin and a trimeric SPSB2/elongin BC complex in the presence of E1 and E2 (UbcH5a) enzymes, Rbx2, and Cullin5 for various times.	SIGNOR-271901
P00519	O60260	1	phosphorylation	down-regulates	0.2	Here we show that the nonreceptor tyrosine kinase c-abl phosphorylates tyrosine 143 of parkin, inhibiting parkin's ubiquitin e3 ligase activity and protective function.	SIGNOR-167853
P46531	Q92630	0	phosphorylation	down-regulates quantity by destabilization	0.288	We demonstrate that DYRK2 phosphorylates Notch1-IC in response to chemotherapeutic agents and facilitates its proteasomal degradation by FBXW7 ubiquitin ligase through a Thr-2512 phosphorylation-dependent mechanism.	SIGNOR-279035
Q9Y5Y9	Q92914	2	binding	down-regulates activity	0.2	Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.	SIGNOR-253442
Q13153	Q9UQ88	0	phosphorylation	up-regulates activity	0.384	CDK11p58 phosphorylation of PAK1 Ser174 promotes DLC2 binding and roles on cell cycle progression\|We show that PAK1 is a substrate of CDK11p58 and can be strongly activated upon phosphorylation.	SIGNOR-273026
Q15796	Q6ZNA4	0	ubiquitination	down-regulates quantity by destabilization	0.685	Arkadia represses the expression of myoblast differentiation markers through degradation of ski and the ski-bound smad complex in c2c12 myoblastsarkadia bound smad2/3 via ski to induce the ubiquitination of smad2/3. These results suggest that arkadia targets ski-bound, inactive phospho-smad2/3 to regulate positively myostatin/tgf-beta signaling.	SIGNOR-236873
P10636	Q13627	0	phosphorylation	down-regulates	0.427	Dyrk1a phosphorylates tau at least at s202, t212 and s404, but t212 phosphorylation is known to initiate tau hyperphosphorylation by gsk3b (ryoo et al., 2007;woods et al., 2001) and has been demonstrated to have a role in alternative splicing of taumrna	SIGNOR-171030
O43541	Q96FA3	2	binding	up-regulates	0.332	Mad6-pellino-1 interaction abrogated signaling mediated by a complex of irak1.	SIGNOR-185128
P0C0S8	P46736	0	deubiquitination	down-regulates	0.2	Brcc36 regulates the abundance of lys(63)-linked ubiquitin chains at chromatin and that one of its substrates is diubiquitinated histone h2a	SIGNOR-167142
Q9Y5I4	P05556	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.	SIGNOR-269033
P58417	P58400	2	binding	up-regulates	0.548	Purification of neurexin ialpha revealed that it is tightly complexed to a secreted glycoprotein called neurexophilin 1	SIGNOR-62699
P17612	P55211	1	phosphorylation	down-regulates	0.2	We show that protein kinase a inhibits activation of caspase-9 and caspase-3 downstream of cytochrome c in xenopus egg extracts and in a human cell-free system. Protein kinase a directly phosphorylates human caspase-9 at serines 99, 183, and 195.	SIGNOR-133884
P09471	Q9HC97	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-256996
P43088	P50148	2	binding	up-regulates activity	0.45	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-257082
P59768	Q99527	2	binding	up-regulates activity	0.385	GPCRs transduce their signal via G-protein heterotrimers (αβγ) that dissociate in free Gα-subunit protein and Gβγ-subunit protein complexes following ligand stimulation; GNG2 stands for the subunit γ, which dissociates from the receptor after the binding of GTP on α-subunit.	SIGNOR-251104
P46527	Q13616	0	ubiquitination	down-regulates quantity by destabilization	0.642	Furthermore, c-myc activation can also promote the degradation of p27kip1 protein by directly activating the cul1 gene, which encodes a critical component of the ubiquitin ligase scfskp2	SIGNOR-102725
P11142	Q9NXW2	2	binding	up-regulates activity	0.509	JB12 cooperates with cytosolic Hsc70 and the ubiquitin ligase RMA1 to target CFTR and CFTRΔF508 for degradation. JB12 drives Hsc70 to associate with CFTR and the RMA1 E3 complex	SIGNOR-271491
Q05655	P14598	1	phosphorylation	up-regulates	0.447	Pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation. The use of p47phox mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc?, ???, And ?.	SIGNOR-89229
Q15759	Q8IW41	1	phosphorylation	up-regulates	0.619	Prak activity was regulated by p38alpha and p38beta both in vitro and in vivo and thr182 was shown to be the regulatory phosphorylation site.	SIGNOR-58131
Q9H6Y7	Q15836	1	ubiquitination	down-regulates quantity by destabilization	0.328	Here, we show that Godzilla/RNF167 regulates endosome recycling by the ubiquitylation of VAMP3 on Lys66, Lys68 and Lys77; namely, two adjacent Lys residues on the both sides of the critical interface of SNARE complex are ubiquitylated. In agreement with VAMP3 being a target for Goliath family ubiquitin ligases, we show that recycling endosome trafficking is abrogated in response to their activity. While we observed ubiquitylation of VAMP3 by Godzilla, we are unable to describe the nature of this ubiquitination, be it mono-ubiquitin or extended ubiquitin chains.	SIGNOR-272093
Q7KZI7	P10636-2	1	phosphorylation	down-regulates activity	0.707	We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.	SIGNOR-275437
Q92830	Q6NXT2	1	acetylation	down-regulates activity	0.2	The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.	SIGNOR-269608
P45983	P63000	2	binding	up-regulates	0.659	The mechanism by which pak1 induced cancer growth might involve activation of jnk in the non-canonical wnt pathway, frizzled uses galfaq or galfai and gbetagamma dimers to activate phospholipase c (plc), resulting in protein kinase c (pkc) activation and calcium mobilization that regulates the transcription factor nfat, and frizzled also signals through the small gtpases rho and rac to c-jun n-terminal kinase (jnk), which activates the ap1 transcription factor.	SIGNOR-152808
Q9BYB0	P42263	2	binding	up-regulates quantity	0.2	SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).	SIGNOR-264603
O15344	Q9P0W2	1	polyubiquitination	down-regulates quantity by destabilization	0.244	The E3 ubiquitin ligase MID1/TRIM18 promotes atypical ubiquitination of the BRCA2-associated factor 35, BRAF35. MID1 is implicated in BRAF35 ubiquitination promoting atypical poly-ubiquitination via K6-, K27- and K29-linkages. We found that MID1 depletion alters BRAF35 localization in these structures and increases BRAF35 stability affecting its cytoplasmic abundance	SIGNOR-272317
P06400	P17480	2	binding	down-regulates activity	0.376	Activity of RNA polymerase I transcription factor UBF blocked by Rb gene product	SIGNOR-262589
O15391	P01100	1	transcriptional regulation	up-regulates quantity by expression	0.392	YY2 activated the p53 promoter. However, in contrast to YY1, which represses the activity of c-Fos, YY2 increased the activity of the c-Fos promoter.	SIGNOR-266212
Q9UJW0	Q01484	0	relocalization	up-regulates quantity	0.625	We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4.	SIGNOR-266713
Q92481	Q15139	0	phosphorylation	down-regulates activity	0.295	Mechanistically, we observed that PKD phosphorylates AP2\u03b2 at Ser-258 and Ser-277 and suppresses its nuclear accumulation.\|Using ChIP analyses, here we found that PKD knockdown in HUVECs increases binding of AP2beta to the VEGFR-2 promoter.	SIGNOR-279267
P43003	Q03135	2	binding	down-regulates activity	0.2	EAAT3 has previously been shown to form complexes with caveolin-1, a major component of caveolae, which participate in the regulation of transport proteins. The present study explored the impact of caveolin-1 on electrogenic transport by excitatory amino acid transporter isoforms EAAT1-4. caveolin-1 is a powerful negative regulator of the excitatory glutamate transporters EAAT1, EAAT2, EAAT3, and EAAT4. Caveolin-1 has been shown to form complexes with the excitatory amino acid transporter EAAT3 (EAAC1) (Gonzalez et al. 2007) and may thus modify the EAAT isoforms by direct interaction with the carriers.	SIGNOR-264808
P54760	P29474	1	phosphorylation	up-regulates activity	0.311	These results suggest that activation of Eph-B4 with Ephrin-B2/Fc stimulates eNOS phosphorylation in vitro (XREF_FIG), eg, eNOS may be a downstream mediator of Eph-B4 signaling in endothelial cells.	SIGNOR-279172
Q14012	Q9Y570	1	phosphorylation	up-regulates activity	0.395	CaMKI Is the Upstream Kinase for Phosphorylation of PME-1/Ser15	SIGNOR-277827
O60674	P48357	2	phosphorylation	up-regulates activity	0.774	LRb signaling is initiated by leptin binding to the extracellular domain of the LRb dimer, leading to Jak2 transphosphorylation and activation. Activated Jak2 mediates the tyrosine phosphorylation of Tyr985 and Tyr1138of LRb. These phosphotyrosine residues immediately function as binding sites (double-ended lines) for SHP-2 and STAT3, both of which quickly become tyrosine-phosphorylated by Jak2.	SIGNOR-263494
P42684	P17931	1	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
P23469	P28482	1	dephosphorylation	down-regulates activity	0.39	The effect of PTP epsilon on ERKs is at least in part indirect because phosphorylation of the threonine residue in the ERK activation loop is reduced in the presence of PTP epsilon. Nonetheless, PTP epsilon is present in a molecular complex with ERK, providing PTP epsilon with opportunity to act on ERK proteins also directly. We conclude that PTP epsilon is a physiological inhibitor of ERK signaling\|These enzymes are joined by the large family of dual-specificity phosphatases, which are structurally similar to tyrosine phosphatases but which can dephosphorylate both residues of the activation loop	SIGNOR-248448
Q8TAM6	O95096	0	transcriptional regulation	up-regulates quantity by expression	0.249	Further study revealed that Nkx2.2 could bind JN promoter and its overexpression increase the promoter activity of JN.	SIGNOR-268965
Q9Y2N7	Q9BXM7	0	phosphorylation	down-regulates activity	0.347	Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ubiquitination to occur.	SIGNOR-263090
P02751	P31431	2	binding	up-regulates activity	0.711	Sdc4 is a high affinity receptor for fibronectin (FN) […] Therefore, we conclude that Sdc4 binds FN on activated satellite cells.	SIGNOR-255846
P53350	O43683	2	phosphorylation	up-regulates activity	0.864	Note that PLK1 phosphorylates and activates BUB1 to localize it to the kinetochore, phosphorylates and inhibits the negative regulator PKMYTI and interacts with the G1/S kinase Cdc7p to target it to initiation complexes late in G1.	SIGNOR-279251
Q9NQA5	P17252	0	phosphorylation	up-regulates activity	0.2	A cell permeable analog of DAG increased TRPV5 activity within 30 min via protein kinase C activation of the channel since mutation of TRPV5 at the putative PKC phosphorylation sites S299 and S654 prevented the stimulatory effect of TK.	SIGNOR-149948
P27986	P63092	2	binding	up-regulates	0.294	Notably, the fzd7 receptor complex was associated with g_?(s) and pi(3)k and these components were required for wnt7a to activate the akt/mtor growth pathway in myotubes. These data led us to hypothesize that g_?s Mediates the activation of pi3kinase following wnt7a binding to fzd7.	SIGNOR-191561
P19544	P00797	1	transcriptional regulation	down-regulates quantity by repression	0.421	Here, we show that a splice variant of the Wilms' tumor protein lacking three amino acids WT1(-KTS) suppresses renin gene transcription	SIGNOR-252296
P06493	P24522	2	binding	down-regulates	0.71	Gadd45 has now been found to directly inhibit the activity of cdc2/cyclin b1 complex	SIGNOR-68221
O60885	Q09472	2	binding	up-regulates activity	0.426	In this study, we explored the role of Brd4 and its interaction with the p300 acetyltransferase in the regulation of Nox4 and the in vivo efficacy of a BET inhibitor to reverse established age-associated lung fibrosis. \|Together, these studies suggest that Brd4 enhances p300-mediated histone acetylation.	SIGNOR-262064
Q03933	Q13618	0	ubiquitination	down-regulates quantity by destabilization	0.326	Here we show that the PEST sequences of a short-lived protein called HSF2 interact with Cullin3, a subunit of a Cullin-RING E3 ubiquitin ligase, and that this interaction mediates the Cul3-dependent ubiquitination and degradation of HSF2	SIGNOR-239129
P55036	O60260	0	polyubiquitination	down-regulates quantity by destabilization	0.2	S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s.	SIGNOR-272749
P62258	P20226	2	binding	up-regulates activity	0.347	The in vitro binding with general transcription factors TBP and TFIIB together with its nuclear location provide evidence supporting a role for 14-3-3 proteins as transcriptional activators or coactivators when part of a DNA binding complex.	SIGNOR-262834
O95628	P41229	1	ubiquitination	down-regulates quantity by destabilization	0.545	In our study, we show that the protein level of the yeast histone H3 Lys 4 (H3 K4) demethylase Jhd2/Kdm5 is modulated through polyubiquitination by the E3 ubiquitin ligase Not4 and turnover by the proteasome. Finally, we show that human NOT4 can polyubiquitinate human JARID1C/SMCX, a homolog of Jhd2, suggesting that this is likely a conserved mechanism. We propose that Not4 is an E3 ubiquitin ligase that monitors and controls a precise amount of Jhd2 protein so that the proper balance between histone demethylase and histone methyltransferase activities occur in the cell, ensuring appropriate levels of H3 K4 trimethylation and gene expression.	SIGNOR-271468
Q04206	P18146	2	binding	up-regulates	0.433	The early growth response transcription factor egr-1 can also interact with rela in vitro and regulate nf-kappab transcriptional activity in vivo	SIGNOR-75001
Q96R06	Q9UJV3	0	ubiquitination	down-regulates quantity by destabilization	0.309	These data indicated that Mid2 was ubiquitinating Astrin at K409 and targeting Astrin for degradation during cytokinesis.	SIGNOR-278549
Q92688	P68400	0	phosphorylation	up-regulates	0.234	Here, we are able to report that casein kinase 2 (ck2) phosphorylates april on residue threonine244 (thr(244)) and demonstrate that the ck2-specific inhibitor 4,5,6,7-tetrabromo-2-azabenzimidazole abolishes cd83 expression in activated jurkat t cells by interfering with the nucleocytoplasmic translocation of cd83 mrna	SIGNOR-183158
Q86YJ5	O60486	1	ubiquitination	down-regulates quantity by destabilization	0.2	MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.	SIGNOR-271532
P10275	P31749	0	phosphorylation	down-regulates activity	0.586	Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor. Here, we demonstrate that akt phosphorylates the androgen receptor (ar) at ser-210 and ser-790	SIGNOR-108508
O95071	P35558	1	ubiquitination	down-regulates quantity by destabilization	0.308	Acetylation Regulates Gluconeogenesis by Promoting PEPCK1 Degradation via Recruiting the UBR5 Ubiquitin Ligase \|UBR5 ubiquitinates the acetylated PEPCK1	SIGNOR-267600
Q8NG68	Q9BQE3	1	tyrosination	down-regulates	0.473	Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization	SIGNOR-176918
O15519	Q14790	2	binding	down-regulates activity	0.771	Flip can be incorporated into the disc complex and blocks processing and activation of pro-caspase8	SIGNOR-96402
Q9GZQ8	Q9NT62	2	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
P52292	Q13131	0	phosphorylation	up-regulates	0.2	Ampk phosphorylated importin alpha1 on ser(105). Accordingly, expression of importin alpha1 proteins bearing k22r or s105a mutations failed to mediate the nuclear import of hur in intact cells. Our results point to importin alpha1 as a critical downstream target of ampk and key mediator of ampk-triggered hur nuclear import.	SIGNOR-128629
Q13131	O00418	1	phosphorylation	down-regulates activity	0.492	AMPK can phosphorylate three sites in eEF2 kinase in vitro. Of these, Ser-398 appears to be more efficiently phosphorylated than either Ser-78 or Ser-366. Ser-78 and Ser-366 do not appear to be phosphorylated by AMPK within cells. Ser-366 serves to decrease the activity of eEF2 kinase	SIGNOR-250314
Q8IVA1	P35398	0	transcriptional regulation	up-regulates quantity by expression	0.2	RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.	SIGNOR-266849
Q96E09	O14757	0	phosphorylation	down-regulates activity	0.2	Knockout of FAM122A results in activation of PP2A-B55α, a phosphatase that dephosphorylates the WEE1 protein and rescues WEE1 from ubiquitin-mediated degradation. in tumor cells with oncogene-driven replication stress, CHK1 can directly phosphorylate FAM122A, leading to activation of the PP2A-B55α phosphatase and increased WEE1 expression.	SIGNOR-266380
Q13177	P08670	1	phosphorylation	down-regulates activity	0.307	In vitro analyses revealed that vimentin served as an excellent substrate for PAK. This phosphorylated vimentin lost the potential to form 10 nm filaments. We identified Ser25, Ser38, Ser50, Ser65 and Ser72 in the amino-terminal head domain as the major phosphorylation sites on vimentin for PAK.	SIGNOR-250243
Q9NZJ5	Q15084	0	null	down-regulates activity	0.2	Protein disulfide isomerase A6 (PDIA6) interacts with protein kinase RNA-like endoplasmic reticulum kinase (PERK) and inositol requiring enzyme (IRE)-1 and inhibits their unfolded protein response signaling.	SIGNOR-256537
P53350	P04049	1	phosphorylation	up-regulates activity	0.289	An in vitro kinase assay demonstrated that PLK1 directly phosphorylated CRAF at S338 and S339, but not at S621 (XREF_FIG).\|These results demonstrate that PLK1 increases the stability of CRAF protein by preventing proteasome degradation.	SIGNOR-278190
P78504	Q8NES3	2	binding	down-regulates	0.486	Although jagged1-induced signaling was suppressed by lfng and mfng	SIGNOR-131560
Q9BRQ8	P04637	0	transcriptional regulation	up-regulates quantity by expression	0.503	The p53 tumor suppressor protein induces cell cycle arrest or apoptosis in response to cellular stresses. We have identified PRG3 (p53-responsive gene 3), which is induced specifically under p53-dependent apoptotic conditions in human colon cancer cells, and encodes a novel polypeptide of 373 amino acids with a predicted molecular mass of 40.5 kDa. these results support the hypothesis that the expression of the PRG3 gene in cells undergoing p53‐dependent apoptosis involves direct activation of its promoter by p53.	SIGNOR-261808
P35222	Q01860	2	binding	up-regulates activity	0.575	We provide evidence suggesting that Beta-catenins interaction with the pluripotency regulator Oct-4 at least partially underlies its effects on sustaining pluripotency.	SIGNOR-241981
P49715	P17947	1	transcriptional regulation	up-regulates quantity by expression	0.528	Activation of C/EBPα induces PU.1 expression, cell cycle arrest, and differentiation in 32D cells expressing FLT3/ITD	SIGNOR-261531
Q99640	P45983	0	phosphorylation	up-regulates	0.336	A kinase assay using gst-myt1 revealed that active jnk1 or jnk3, but not jnk2, phosphorylated myt1 in vitro.	SIGNOR-183899
P23443	O60825	1	phosphorylation	up-regulates activity	0.247	Heart 6-phosphofructo-2-kinase activation by insulin results from ser-466 and ser-483 phosphorylation and requires 3-phosphoinositide-dependent kinase-1, but not protein kinase b.	SIGNOR-49371
P62136	P31749	1	dephosphorylation	down-regulates activity	0.426	Here, we identify PP1 as a serine/threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells\|The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells	SIGNOR-252603
P38405	Q13258	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-256898
P08247	P63027	2	binding	up-regulates quantity	0.6	Synaptophysin I interacts with VAMP2 and controls its subcellular distribution. On the SV membrane, VAMP2 is engaged in a complex with synaptophysin I, which is mutually exclusive with the formation of fusogenic SNARE complexes. This model implicates synaptophysin I in escorting VAMP2 to the sites where exocytosis must take place exclusively after the arrival of the appropriate stimulus. We show that, at early stages along the secretory pathway, synaptophysin I directs sorting of VAMP2 to vesicles exhibiting limited availability for constitutive exocytosis.	SIGNOR-264102
Q14160	P35222	2	binding	up-regulates activity	0.434	Cadherins mediate the localization of vesicles to presynaptic compartments through multiple mechanisms. Cadherin-bound β-catenin then recruits scribble (Scrib) which acts as a scaffold for the further recruitment of proteins that mediate the localization of SVs.	SIGNOR-265826
O14920	Q13148	1	phosphorylation	down-regulates quantity by destabilization	0.2	IκB kinase phosphorylates cytoplasmic TDP-43 and promotes its proteasome degradation. Furthermore, we identified IKKβ-induced phosphorylation sites of TDP-43 and found that phosphorylation at Thr8 and Ser92 is important for the reduction of TDP-43 by IKK.	SIGNOR-277860
Q04206	P67775	0	dephosphorylation	down-regulates	0.483	Rela was dephosphorylated by a purified pp2a core enzyme, a heterodimer formed by the catalytic subunit of pp2a (pp2ac) and pr65, in a concentration-dependent manner.These data suggest that the constitutive activation of rela in melanoma cells could be due, at least in part, to the deficiency of pp2a, which exhibits decreased dephosphorylation of nf-kappa b/rela.	SIGNOR-110959
P00558	P00558	2	phosphorylation	up-regulates activity	0.2	PGK1 functions not only as a glycolytic enzyme but also as a protein kinase intermolecularly autophosphorylating itself at Y324 for activation.	SIGNOR-277482
O75093	Q14938	0	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268906
Q99250	Q92914	2	binding	down-regulates activity	0.252	Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.	SIGNOR-253430
P42768	Q06187	0	phosphorylation	up-regulates activity	0.743	These results demonstrate that WASP, under this experimental condition, can be tyrosine-phosphorylated by the kinase activity of Btk and that the direct interaction between WASP and the SH3 domain of Btk is required for this phosphorylation to occur.	SIGNOR-273958
Q05655	Q05655	2	phosphorylation	up-regulates	0.2	This study identifies novel in vitro pkcdelta autophosphorylation sites at thr(141) adjacent to the pseudosubstrate domain, thr(218) in the c1a-c1b interdomain, ser(295), ser(302), and ser(304) in the hinge region, and ser(503) adjacent to thr(505) in the activation loop. studies reported herein show that a t505a substitution reduces pkcdelta-thr(295) autophosphorylation	SIGNOR-185287
P49841	P49768	1	phosphorylation	down-regulates activity	0.586	We demonstrate that phosphorylation of serines 353 and 357 by glycogen synthase kinase-3beta (gsk3beta) induces a structural change of the hydrophilic loop of ps1the structural change of ps1 reduces the interaction with beta-catenin leading to decreased phosphorylation and ubiquitination of beta-catenin.	SIGNOR-153627
O15550	P31270	1	transcriptional regulation	up-regulates quantity by expression	0.263	Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.	SIGNOR-260021
P02818	P07858	0	cleavage	down-regulates quantity by destabilization	0.33	This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42.	SIGNOR-256318
Q96T49	P17252	0	phosphorylation	down-regulates activity	0.2	PKCα phosphorylated the full length recombinant TIMAP in in vitro kinase assay and Ser331 of TIMAP was shown to be phosphorylated by PKC. Phosphorylation of TIMAP upon PKC activation in endothelial cells results in enrichment of TIMAP in the membrane, but no such change can be observed in PKC depleted cells. Phosphorylation state of TIMAP, through affecting PP1 activity, has a remarkable effect on endothelial barrier function.	SIGNOR-273802
Q9BRS2	Q9HBM1	2	binding	up-regulates activity	0.2	This study demonstrates that SPC25 acts as a molecular scaffold, mediating SPC25/RIOK1/MYH9 complex formation and triggering the RIOK1‐mediated phosphorylation of MYH9 at Ser1943.Taken together, these results suggested that SPC25 increases MYH9 phosphorylation at Ser1943, enhancing the nuclear accumulation of MYH9 and consequently modulating the transcription of CTNNB1.	SIGNOR-278893
P27361	P46527	1	phosphorylation	down-regulates	0.376	These data suggest that increased signaling by erbb receptors up-regulates mapk activity, which, in turn, phosphorylates and destabilizes p27, thus contributing to dysregulated cell cycle progression.	SIGNOR-80234
P0C0L5	P48740	0	cleavage	up-regulates activity	0.676	The classical complement activation pathway, like the MELinitiated pathway, involves the generation of a C3-converting complex, C4b2b, through enzymatic activation of C4 and C2. In the C1 complex (C1qr2s2), this specific protease activity is exhibited by C1s after activation of this enzyme by C1r. When C4 is activated, its reactive thiol ester is exposed and C4b binds covalently to nearby amino or hydroxyl groups. The C4-activating abilities of MASP-1 and MASP-2 were compared.\|Activation of C4 by Ct sand MASP-2 on western blots.	SIGNOR-263426
P01100	P26439	1	transcriptional regulation	up-regulates quantity by expression	0.2	We found that both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters.	SIGNOR-254877
P46734	O15264	1	phosphorylation	up-regulates activity	0.607	p38-δ is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7. we investigated whether this Thr180-Gly-Tyr182 motif was essential for p38-δ activation. Taken together, these results suggest that the dual phosphorylation TGY motif is required for p38-δ activation.	SIGNOR-273950
P17302	Q13164	0	phosphorylation	down-regulates activity	0.54	Activated BMK1 selectively phosphorylates Cx43 on Ser-255 in vitro and in vivo. These data demonstrate that BMK1 kinase activity alone is both a necessary and sufficient component in the mediation of EGF-induced Cx43 Ser-255 phosphorylation and subsequent inhibition of GJC.	SIGNOR-250115
P12757	Q9UM11	2	binding	down-regulates quantity by destabilization	0.385	We demonstrate that the anaphase-promoting complex (APC) is a ubiquitin ligase required for the destruction of SnoN and that the APC pathway is regulated by TGF-beta. The destruction box of SnoN is required for its degradation in response to TGF-beta signaling. Furthermore, the APC activator CDH1 and Smad3 synergistically regulate SnoN degradation. Under these circumstances, CDH1 forms a quaternary complex with SnoN, Smad3, and APC.	SIGNOR-272621
P01111	P10398	2	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
P17302	Q02156	0	phosphorylation	down-regulates activity	0.44	Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication.\|These data strongly suggest that PKC directly phosphorylates Cx43 on S368 in vivo, which results in a change in single channel behavior that contributes to a decrease in intercellular communication.	SIGNOR-144465
Q13480	P28482	0	phosphorylation	up-regulates activity	0.602	Our results demonstrate that ERK1/2 phosphorylate Gab1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) in consensus motifs for MAP kinase phosphorylation. \|serine and threonine phosphorylation are capable of modulating the initial signal	SIGNOR-249395
Q5S007	P35241	1	phosphorylation	up-regulates activity	0.364	LRRK2 also phosphorylated ezrin and radixin, which are related to moesin, at the residue equivalent to Thr558, as well as a peptide (LRRKtide: RLGRDKYKTLRQIRQ) encompassing Thr558.	SIGNOR-279203
P15056	Q8NC42	0	polyubiquitination	down-regulates quantity by destabilization	0.337	We showed that RNF149 bound directly to the C-terminal kinase-containing domain of wild-type BRAF and induced ubiquitination, followed by proteasome-dependent degradation, of the latter protein. Functionally, RNF149 attenuated the increase in cell growth induced by wild-type BRAF.	SIGNOR-272043
Q13131	Q8IWQ3	0	phosphorylation	up-regulates	0.291	Ampka1 activators increased phosphorylation level and cytoplasmic localization (reduced nuclear/cytoplasmic ratio). Ampka1 activators reduced rna synthesis in the nucleoli.	SIGNOR-176594

O60674

P28482

0

phosphorylation

down-regulates

0.513

We hypothesize that phosphorylation of ser523 in jak2 by erks 1 and/or 2 or other as-yet-unidentified kinases acts in a negative feedback manner

SIGNOR-236331

Q9BUB5

P47712

1

phosphorylation

up-regulates activity

0.577

The results suggest that MNK1 or a closely related kinase is responsible for in vivo phosphorylation of cPLA2 on Ser-727.

SIGNOR-226633

Q99619

P60321

2

binding

down-regulates quantity by destabilization

0.2

We have identified SPRY domain-containing SOCS (suppressor of cytokine signaling) box protein 2 (SPSB2) as a novel negative regulator that recruits an E3 ubiquitin ligase complex to polyubiquitinate iNOS, resulting in its proteasomal degradation. A cell-free ubiquitination assay was established to demonstrate SPSB2-dependent ubiquitination of iNOS. LPS/IFN-γ–stimulated macrophage lysates from Spsb2−/− mice were used as a source of iNOS and incubated with ubiquitin and a trimeric SPSB2/elongin BC complex in the presence of E1 and E2 (UbcH5a) enzymes, Rbx2, and Cullin5 for various times.

SIGNOR-271901

P00519

O60260

1

phosphorylation

down-regulates

0.2

Here we show that the nonreceptor tyrosine kinase c-abl phosphorylates tyrosine 143 of parkin, inhibiting parkin's ubiquitin e3 ligase activity and protective function.

SIGNOR-167853

P46531

Q92630

0

phosphorylation

down-regulates quantity by destabilization

0.288

We demonstrate that DYRK2 phosphorylates Notch1-IC in response to chemotherapeutic agents and facilitates its proteasomal degradation by FBXW7 ubiquitin ligase through a Thr-2512 phosphorylation-dependent mechanism.

SIGNOR-279035

Q9Y5Y9

Q92914

2

binding

down-regulates activity

0.2

Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.

SIGNOR-253442

Q13153

Q9UQ88

0

phosphorylation

up-regulates activity

0.384

CDK11p58 phosphorylation of PAK1 Ser174 promotes DLC2 binding and roles on cell cycle progression|We show that PAK1 is a substrate of CDK11p58 and can be strongly activated upon phosphorylation.

SIGNOR-273026

Q15796

Q6ZNA4

0

ubiquitination

down-regulates quantity by destabilization

0.685

Arkadia represses the expression of myoblast differentiation markers through degradation of ski and the ski-bound smad complex in c2c12 myoblastsarkadia bound smad2/3 via ski to induce the ubiquitination of smad2/3. These results suggest that arkadia targets ski-bound, inactive phospho-smad2/3 to regulate positively myostatin/tgf-beta signaling.

SIGNOR-236873

P10636

Q13627

0

phosphorylation

down-regulates

0.427

Dyrk1a phosphorylates tau at least at s202, t212 and s404, but t212 phosphorylation is known to initiate tau hyperphosphorylation by gsk3b (ryoo et al., 2007;woods et al., 2001) and has been demonstrated to have a role in alternative splicing of taumrna

SIGNOR-171030

O43541

Q96FA3

2

binding

up-regulates

0.332

Mad6-pellino-1 interaction abrogated signaling mediated by a complex of irak1.

SIGNOR-185128

P0C0S8

P46736

0

deubiquitination

down-regulates

0.2

Brcc36 regulates the abundance of lys(63)-linked ubiquitin chains at chromatin and that one of its substrates is diubiquitinated histone h2a

SIGNOR-167142

Q9Y5I4

P05556

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.

SIGNOR-269033

P58417

P58400

2

binding

up-regulates

0.548

Purification of neurexin ialpha revealed that it is tightly complexed to a secreted glycoprotein called neurexophilin 1

SIGNOR-62699

P17612

P55211

1

phosphorylation

down-regulates

0.2

We show that protein kinase a inhibits activation of caspase-9 and caspase-3 downstream of cytochrome c in xenopus egg extracts and in a human cell-free system. Protein kinase a directly phosphorylates human caspase-9 at serines 99, 183, and 195.

SIGNOR-133884

P09471

Q9HC97

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-256996

P43088

P50148

2

binding

up-regulates activity

0.45

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-257082

P59768

Q99527

2

binding

up-regulates activity

0.385

GPCRs transduce their signal via G-protein heterotrimers (αβγ) that dissociate in free Gα-subunit protein and Gβγ-subunit protein complexes following ligand stimulation; GNG2 stands for the subunit γ, which dissociates from the receptor after the binding of GTP on α-subunit.

SIGNOR-251104

P46527

Q13616

0

ubiquitination

down-regulates quantity by destabilization

0.642

Furthermore, c-myc activation can also promote the degradation of p27kip1 protein by directly activating the cul1 gene, which encodes a critical component of the ubiquitin ligase scfskp2

SIGNOR-102725

P11142

Q9NXW2

2

binding

up-regulates activity

0.509

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

SIGNOR-271491

Q05655

P14598

1

phosphorylation

up-regulates

0.447

Pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation. The use of p47phox mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc?, ???, And ?.

SIGNOR-89229

Q15759

Q8IW41

1

phosphorylation

up-regulates

0.619

Prak activity was regulated by p38alpha and p38beta both in vitro and in vivo and thr182 was shown to be the regulatory phosphorylation site.

SIGNOR-58131

Q9H6Y7

Q15836

1

ubiquitination

down-regulates quantity by destabilization

0.328

Here, we show that Godzilla/RNF167 regulates endosome recycling by the ubiquitylation of VAMP3 on Lys66, Lys68 and Lys77; namely, two adjacent Lys residues on the both sides of the critical interface of SNARE complex are ubiquitylated. In agreement with VAMP3 being a target for Goliath family ubiquitin ligases, we show that recycling endosome trafficking is abrogated in response to their activity. While we observed ubiquitylation of VAMP3 by Godzilla, we are unable to describe the nature of this ubiquitination, be it mono-ubiquitin or extended ubiquitin chains.

SIGNOR-272093

Q7KZI7

P10636-2

1

phosphorylation

down-regulates activity

0.707

We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.

SIGNOR-275437

Q92830

Q6NXT2

1

acetylation

down-regulates activity

0.2

The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.

SIGNOR-269608

P45983

P63000

2

binding

up-regulates

0.659

The mechanism by which pak1 induced cancer growth might involve activation of jnk in the non-canonical wnt pathway, frizzled uses galfaq or galfai and gbetagamma dimers to activate phospholipase c (plc), resulting in protein kinase c (pkc) activation and calcium mobilization that regulates the transcription factor nfat, and frizzled also signals through the small gtpases rho and rac to c-jun n-terminal kinase (jnk), which activates the ap1 transcription factor.

SIGNOR-152808

Q9BYB0

P42263

2

binding

up-regulates quantity

0.2

SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).

SIGNOR-264603

O15344

Q9P0W2

1

polyubiquitination

down-regulates quantity by destabilization

0.244

The E3 ubiquitin ligase MID1/TRIM18 promotes atypical ubiquitination of the BRCA2-associated factor 35, BRAF35. MID1 is implicated in BRAF35 ubiquitination promoting atypical poly-ubiquitination via K6-, K27- and K29-linkages. We found that MID1 depletion alters BRAF35 localization in these structures and increases BRAF35 stability affecting its cytoplasmic abundance

SIGNOR-272317

P06400

P17480

2

binding

down-regulates activity

0.376

Activity of RNA polymerase I transcription factor UBF blocked by Rb gene product

SIGNOR-262589

O15391

P01100

1

transcriptional regulation

up-regulates quantity by expression

0.392

YY2 activated the p53 promoter. However, in contrast to YY1, which represses the activity of c-Fos, YY2 increased the activity of the c-Fos promoter.

SIGNOR-266212

Q9UJW0

Q01484

0

relocalization

up-regulates quantity

0.625

We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4.

SIGNOR-266713

Q92481

Q15139

0

phosphorylation

down-regulates activity

0.295

Mechanistically, we observed that PKD phosphorylates AP2\u03b2 at Ser-258 and Ser-277 and suppresses its nuclear accumulation.|Using ChIP analyses, here we found that PKD knockdown in HUVECs increases binding of AP2beta to the VEGFR-2 promoter.

SIGNOR-279267

P43003

Q03135

2

binding

down-regulates activity

0.2

EAAT3 has previously been shown to form complexes with caveolin-1, a major component of caveolae, which participate in the regulation of transport proteins. The present study explored the impact of caveolin-1 on electrogenic transport by excitatory amino acid transporter isoforms EAAT1-4. caveolin-1 is a powerful negative regulator of the excitatory glutamate transporters EAAT1, EAAT2, EAAT3, and EAAT4. Caveolin-1 has been shown to form complexes with the excitatory amino acid transporter EAAT3 (EAAC1) (Gonzalez et al. 2007) and may thus modify the EAAT isoforms by direct interaction with the carriers.

SIGNOR-264808

P54760

P29474

1

phosphorylation

up-regulates activity

0.311

These results suggest that activation of Eph-B4 with Ephrin-B2/Fc stimulates eNOS phosphorylation in vitro (XREF_FIG), eg, eNOS may be a downstream mediator of Eph-B4 signaling in endothelial cells.

SIGNOR-279172

Q14012

Q9Y570

1

phosphorylation

up-regulates activity

0.395

CaMKI Is the Upstream Kinase for Phosphorylation of PME-1/Ser15

SIGNOR-277827

O60674

P48357

2

phosphorylation

up-regulates activity

0.774

LRb signaling is initiated by leptin binding to the extracellular domain of the LRb dimer, leading to Jak2 transphosphorylation and activation. Activated Jak2 mediates the tyrosine phosphorylation of Tyr985 and Tyr1138of LRb. These phosphotyrosine residues immediately function as binding sites (double-ended lines) for SHP-2 and STAT3, both of which quickly become tyrosine-phosphorylated by Jak2.

SIGNOR-263494

P42684

P17931

1

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

P23469

P28482

1

dephosphorylation

down-regulates activity

0.39

The effect of PTP epsilon on ERKs is at least in part indirect because phosphorylation of the threonine residue in the ERK activation loop is reduced in the presence of PTP epsilon. Nonetheless, PTP epsilon is present in a molecular complex with ERK, providing PTP epsilon with opportunity to act on ERK proteins also directly. We conclude that PTP epsilon is a physiological inhibitor of ERK signaling|These enzymes are joined by the large family of dual-specificity phosphatases, which are structurally similar to tyrosine phosphatases but which can dephosphorylate both residues of the activation loop

SIGNOR-248448

Q8TAM6

O95096

0

transcriptional regulation

up-regulates quantity by expression

0.249

Further study revealed that Nkx2.2 could bind JN promoter and its overexpression increase the promoter activity of JN.

SIGNOR-268965

Q9Y2N7

Q9BXM7

0

phosphorylation

down-regulates activity

0.347

Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ubiquitination to occur.

SIGNOR-263090

P02751

P31431

2

binding

up-regulates activity

0.711

Sdc4 is a high affinity receptor for fibronectin (FN) […] Therefore, we conclude that Sdc4 binds FN on activated satellite cells.

SIGNOR-255846

P53350

O43683

2

phosphorylation

up-regulates activity

0.864

Note that PLK1 phosphorylates and activates BUB1 to localize it to the kinetochore, phosphorylates and inhibits the negative regulator PKMYTI and interacts with the G1/S kinase Cdc7p to target it to initiation complexes late in G1.

SIGNOR-279251

Q9NQA5

P17252

0

phosphorylation

up-regulates activity

0.2

A cell permeable analog of DAG increased TRPV5 activity within 30 min via protein kinase C activation of the channel since mutation of TRPV5 at the putative PKC phosphorylation sites S299 and S654 prevented the stimulatory effect of TK.

SIGNOR-149948

P27986

P63092

2

binding

up-regulates

0.294

Notably, the fzd7 receptor complex was associated with g_?(s) and pi(3)k and these components were required for wnt7a to activate the akt/mtor growth pathway in myotubes. These data led us to hypothesize that g_?s Mediates the activation of pi3kinase following wnt7a binding to fzd7.

SIGNOR-191561

P19544

P00797

1

transcriptional regulation

down-regulates quantity by repression

0.421

Here, we show that a splice variant of the Wilms' tumor protein lacking three amino acids WT1(-KTS) suppresses renin gene transcription

SIGNOR-252296

P06493

P24522

2

binding

down-regulates

0.71

Gadd45 has now been found to directly inhibit the activity of cdc2/cyclin b1 complex

SIGNOR-68221

O60885

Q09472

2

binding

up-regulates activity

0.426

In this study, we explored the role of Brd4 and its interaction with the p300 acetyltransferase in the regulation of Nox4 and the in vivo efficacy of a BET inhibitor to reverse established age-associated lung fibrosis. |Together, these studies suggest that Brd4 enhances p300-mediated histone acetylation.

SIGNOR-262064

Q03933

Q13618

0

ubiquitination

down-regulates quantity by destabilization

0.326

Here we show that the PEST sequences of a short-lived protein called HSF2 interact with Cullin3, a subunit of a Cullin-RING E3 ubiquitin ligase, and that this interaction mediates the Cul3-dependent ubiquitination and degradation of HSF2

SIGNOR-239129

P55036

O60260

0

polyubiquitination

down-regulates quantity by destabilization

0.2

S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s.

SIGNOR-272749

P62258

P20226

2

binding

up-regulates activity

0.347

The in vitro binding with general transcription factors TBP and TFIIB together with its nuclear location provide evidence supporting a role for 14-3-3 proteins as transcriptional activators or coactivators when part of a DNA binding complex.

SIGNOR-262834

O95628

P41229

1

ubiquitination

down-regulates quantity by destabilization

0.545

In our study, we show that the protein level of the yeast histone H3 Lys 4 (H3 K4) demethylase Jhd2/Kdm5 is modulated through polyubiquitination by the E3 ubiquitin ligase Not4 and turnover by the proteasome. Finally, we show that human NOT4 can polyubiquitinate human JARID1C/SMCX, a homolog of Jhd2, suggesting that this is likely a conserved mechanism. We propose that Not4 is an E3 ubiquitin ligase that monitors and controls a precise amount of Jhd2 protein so that the proper balance between histone demethylase and histone methyltransferase activities occur in the cell, ensuring appropriate levels of H3 K4 trimethylation and gene expression.

SIGNOR-271468

Q04206

P18146

2

binding

up-regulates

0.433

The early growth response transcription factor egr-1 can also interact with rela in vitro and regulate nf-kappab transcriptional activity in vivo

SIGNOR-75001

Q96R06

Q9UJV3

0

ubiquitination

down-regulates quantity by destabilization

0.309

These data indicated that Mid2 was ubiquitinating Astrin at K409 and targeting Astrin for degradation during cytokinesis.

SIGNOR-278549

Q92688

P68400

0

phosphorylation

up-regulates

0.234

Here, we are able to report that casein kinase 2 (ck2) phosphorylates april on residue threonine244 (thr(244)) and demonstrate that the ck2-specific inhibitor 4,5,6,7-tetrabromo-2-azabenzimidazole abolishes cd83 expression in activated jurkat t cells by interfering with the nucleocytoplasmic translocation of cd83 mrna

SIGNOR-183158

Q86YJ5

O60486

1

ubiquitination

down-regulates quantity by destabilization

0.2

MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.

SIGNOR-271532

P10275

P31749

0

phosphorylation

down-regulates activity

0.586

Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor. Here, we demonstrate that akt phosphorylates the androgen receptor (ar) at ser-210 and ser-790

SIGNOR-108508

O95071

P35558

1

ubiquitination

down-regulates quantity by destabilization

0.308

Acetylation Regulates Gluconeogenesis by Promoting PEPCK1 Degradation via Recruiting the UBR5 Ubiquitin Ligase |UBR5 ubiquitinates the acetylated PEPCK1

SIGNOR-267600

Q8NG68

Q9BQE3

1

tyrosination

down-regulates

0.473

Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization

SIGNOR-176918

O15519

Q14790

2

binding

down-regulates activity

0.771

Flip can be incorporated into the disc complex and blocks processing and activation of pro-caspase8

SIGNOR-96402

Q9GZQ8

Q9NT62

2

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

P52292

Q13131

0

phosphorylation

up-regulates

0.2

Ampk phosphorylated importin alpha1 on ser(105). Accordingly, expression of importin alpha1 proteins bearing k22r or s105a mutations failed to mediate the nuclear import of hur in intact cells. Our results point to importin alpha1 as a critical downstream target of ampk and key mediator of ampk-triggered hur nuclear import.

SIGNOR-128629

Q13131

O00418

1

phosphorylation

down-regulates activity

0.492

AMPK can phosphorylate three sites in eEF2 kinase in vitro. Of these, Ser-398 appears to be more efficiently phosphorylated than either Ser-78 or Ser-366. Ser-78 and Ser-366 do not appear to be phosphorylated by AMPK within cells. Ser-366 serves to decrease the activity of eEF2 kinase

SIGNOR-250314

Q8IVA1

P35398

0

transcriptional regulation

up-regulates quantity by expression

0.2

RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.

SIGNOR-266849

Q96E09

O14757

0

phosphorylation

down-regulates activity

0.2

Knockout of FAM122A results in activation of PP2A-B55α, a phosphatase that dephosphorylates the WEE1 protein and rescues WEE1 from ubiquitin-mediated degradation. in tumor cells with oncogene-driven replication stress, CHK1 can directly phosphorylate FAM122A, leading to activation of the PP2A-B55α phosphatase and increased WEE1 expression.

SIGNOR-266380

Q13177

P08670

1

phosphorylation

down-regulates activity

0.307

In vitro analyses revealed that vimentin served as an excellent substrate for PAK. This phosphorylated vimentin lost the potential to form 10 nm filaments. We identified Ser25, Ser38, Ser50, Ser65 and Ser72 in the amino-terminal head domain as the major phosphorylation sites on vimentin for PAK.

SIGNOR-250243

Q9NZJ5

Q15084

0

null

down-regulates activity

0.2

Protein disulfide isomerase A6 (PDIA6) interacts with protein kinase RNA-like endoplasmic reticulum kinase (PERK) and inositol requiring enzyme (IRE)-1 and inhibits their unfolded protein response signaling.

SIGNOR-256537

P53350

P04049

1

phosphorylation

up-regulates activity

0.289

An in vitro kinase assay demonstrated that PLK1 directly phosphorylated CRAF at S338 and S339, but not at S621 (XREF_FIG).|These results demonstrate that PLK1 increases the stability of CRAF protein by preventing proteasome degradation.

SIGNOR-278190

P78504

Q8NES3

2

binding

down-regulates

0.486

Although jagged1-induced signaling was suppressed by lfng and mfng

SIGNOR-131560

Q9BRQ8

P04637

0

transcriptional regulation

up-regulates quantity by expression

0.503

The p53 tumor suppressor protein induces cell cycle arrest or apoptosis in response to cellular stresses. We have identified PRG3 (p53-responsive gene 3), which is induced specifically under p53-dependent apoptotic conditions in human colon cancer cells, and encodes a novel polypeptide of 373 amino acids with a predicted molecular mass of 40.5 kDa. these results support the hypothesis that the expression of the PRG3 gene in cells undergoing p53‐dependent apoptosis involves direct activation of its promoter by p53.

SIGNOR-261808

P35222

Q01860

2

binding

up-regulates activity

0.575

We provide evidence suggesting that Beta-catenins interaction with the pluripotency regulator Oct-4 at least partially underlies its effects on sustaining pluripotency.

SIGNOR-241981

P49715

P17947

1

transcriptional regulation

up-regulates quantity by expression

0.528

Activation of C/EBPα induces PU.1 expression, cell cycle arrest, and differentiation in 32D cells expressing FLT3/ITD

SIGNOR-261531

Q99640

P45983

0

phosphorylation

up-regulates

0.336

A kinase assay using gst-myt1 revealed that active jnk1 or jnk3, but not jnk2, phosphorylated myt1 in vitro.

SIGNOR-183899

P23443

O60825

1

phosphorylation

up-regulates activity

0.247

Heart 6-phosphofructo-2-kinase activation by insulin results from ser-466 and ser-483 phosphorylation and requires 3-phosphoinositide-dependent kinase-1, but not protein kinase b.

SIGNOR-49371

P62136

P31749

1

dephosphorylation

down-regulates activity

0.426

Here, we identify PP1 as a serine/threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells|The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells

SIGNOR-252603

P38405

Q13258

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-256898

P08247

P63027

2

binding

up-regulates quantity

0.6

Synaptophysin I interacts with VAMP2 and controls its subcellular distribution. On the SV membrane, VAMP2 is engaged in a complex with synaptophysin I, which is mutually exclusive with the formation of fusogenic SNARE complexes. This model implicates synaptophysin I in escorting VAMP2 to the sites where exocytosis must take place exclusively after the arrival of the appropriate stimulus. We show that, at early stages along the secretory pathway, synaptophysin I directs sorting of VAMP2 to vesicles exhibiting limited availability for constitutive exocytosis.

SIGNOR-264102

Q14160

P35222

2

binding

up-regulates activity

0.434

Cadherins mediate the localization of vesicles to presynaptic compartments through multiple mechanisms. Cadherin-bound β-catenin then recruits scribble (Scrib) which acts as a scaffold for the further recruitment of proteins that mediate the localization of SVs.

SIGNOR-265826

O14920

Q13148

1

phosphorylation

down-regulates quantity by destabilization

0.2

IκB kinase phosphorylates cytoplasmic TDP-43 and promotes its proteasome degradation. Furthermore, we identified IKKβ-induced phosphorylation sites of TDP-43 and found that phosphorylation at Thr8 and Ser92 is important for the reduction of TDP-43 by IKK.

SIGNOR-277860

Q04206

P67775

0

dephosphorylation

down-regulates

0.483

Rela was dephosphorylated by a purified pp2a core enzyme, a heterodimer formed by the catalytic subunit of pp2a (pp2ac) and pr65, in a concentration-dependent manner.These data suggest that the constitutive activation of rela in melanoma cells could be due, at least in part, to the deficiency of pp2a, which exhibits decreased dephosphorylation of nf-kappa b/rela.

SIGNOR-110959

P00558

2

phosphorylation

up-regulates activity

0.2

PGK1 functions not only as a glycolytic enzyme but also as a protein kinase intermolecularly autophosphorylating itself at Y324 for activation.

SIGNOR-277482

O75093

Q14938

0

transcriptional regulation

up-regulates quantity

0.2

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

SIGNOR-268906

Q99250

Q92914

2

binding

down-regulates activity

0.252

Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.

SIGNOR-253430

P42768

Q06187

0

phosphorylation

up-regulates activity

0.743

These results demonstrate that WASP, under this experimental condition, can be tyrosine-phosphorylated by the kinase activity of Btk and that the direct interaction between WASP and the SH3 domain of Btk is required for this phosphorylation to occur.

SIGNOR-273958

Q05655

2

phosphorylation

up-regulates

0.2

This study identifies novel in vitro pkcdelta autophosphorylation sites at thr(141) adjacent to the pseudosubstrate domain, thr(218) in the c1a-c1b interdomain, ser(295), ser(302), and ser(304) in the hinge region, and ser(503) adjacent to thr(505) in the activation loop. studies reported herein show that a t505a substitution reduces pkcdelta-thr(295) autophosphorylation

SIGNOR-185287

P49841

P49768

1

phosphorylation

down-regulates activity

0.586

We demonstrate that phosphorylation of serines 353 and 357 by glycogen synthase kinase-3beta (gsk3beta) induces a structural change of the hydrophilic loop of ps1the structural change of ps1 reduces the interaction with beta-catenin leading to decreased phosphorylation and ubiquitination of beta-catenin.

SIGNOR-153627

O15550

P31270

1

transcriptional regulation

up-regulates quantity by expression

0.263

Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.

SIGNOR-260021

P02818

P07858

0

cleavage

down-regulates quantity by destabilization

0.33

This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42.

SIGNOR-256318

Q96T49

P17252

0

phosphorylation

down-regulates activity

0.2

PKCα phosphorylated the full length recombinant TIMAP in in vitro kinase assay and Ser331 of TIMAP was shown to be phosphorylated by PKC. Phosphorylation of TIMAP upon PKC activation in endothelial cells results in enrichment of TIMAP in the membrane, but no such change can be observed in PKC depleted cells. Phosphorylation state of TIMAP, through affecting PP1 activity, has a remarkable effect on endothelial barrier function.

SIGNOR-273802

Q9BRS2

Q9HBM1

2

binding

up-regulates activity

0.2

This study demonstrates that SPC25 acts as a molecular scaffold, mediating SPC25/RIOK1/MYH9 complex formation and triggering the RIOK1‐mediated phosphorylation of MYH9 at Ser1943.Taken together, these results suggested that SPC25 increases MYH9 phosphorylation at Ser1943, enhancing the nuclear accumulation of MYH9 and consequently modulating the transcription of CTNNB1.

SIGNOR-278893

P27361

P46527

1

phosphorylation

down-regulates

0.376

These data suggest that increased signaling by erbb receptors up-regulates mapk activity, which, in turn, phosphorylates and destabilizes p27, thus contributing to dysregulated cell cycle progression.

SIGNOR-80234

P0C0L5

P48740

0

cleavage

up-regulates activity

0.676

The classical complement activation pathway, like the MELinitiated pathway, involves the generation of a C3-converting complex, C4b2b, through enzymatic activation of C4 and C2. In the C1 complex (C1qr2s2), this specific protease activity is exhibited by C1s after activation of this enzyme by C1r. When C4 is activated, its reactive thiol ester is exposed and C4b binds covalently to nearby amino or hydroxyl groups. The C4-activating abilities of MASP-1 and MASP-2 were compared.|Activation of C4 by Ct sand MASP-2 on western blots.

SIGNOR-263426

P01100

P26439

1

transcriptional regulation

up-regulates quantity by expression

0.2

We found that both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters.

SIGNOR-254877

P46734

O15264

1

phosphorylation

up-regulates activity

0.607

p38-δ is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7. we investigated whether this Thr180-Gly-Tyr182 motif was essential for p38-δ activation. Taken together, these results suggest that the dual phosphorylation TGY motif is required for p38-δ activation.

SIGNOR-273950

P17302

Q13164

0

phosphorylation

down-regulates activity

0.54

Activated BMK1 selectively phosphorylates Cx43 on Ser-255 in vitro and in vivo. These data demonstrate that BMK1 kinase activity alone is both a necessary and sufficient component in the mediation of EGF-induced Cx43 Ser-255 phosphorylation and subsequent inhibition of GJC.

SIGNOR-250115

P12757

Q9UM11

2

binding

down-regulates quantity by destabilization

0.385

We demonstrate that the anaphase-promoting complex (APC) is a ubiquitin ligase required for the destruction of SnoN and that the APC pathway is regulated by TGF-beta. The destruction box of SnoN is required for its degradation in response to TGF-beta signaling. Furthermore, the APC activator CDH1 and Smad3 synergistically regulate SnoN degradation. Under these circumstances, CDH1 forms a quaternary complex with SnoN, Smad3, and APC.

SIGNOR-272621

P01111

P10398

2

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

P17302

Q02156

0

phosphorylation

down-regulates activity

0.44

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

SIGNOR-144465

Q13480

P28482

0

phosphorylation

up-regulates activity

0.602

Our results demonstrate that ERK1/2 phosphorylate Gab1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) in consensus motifs for MAP kinase phosphorylation. |serine and threonine phosphorylation are capable of modulating the initial signal

SIGNOR-249395

Q5S007

P35241

1

phosphorylation

up-regulates activity

0.364

LRRK2 also phosphorylated ezrin and radixin, which are related to moesin, at the residue equivalent to Thr558, as well as a peptide (LRRKtide: RLGRDKYKTLRQIRQ) encompassing Thr558.

SIGNOR-279203

P15056

Q8NC42

0

polyubiquitination

down-regulates quantity by destabilization

0.337

We showed that RNF149 bound directly to the C-terminal kinase-containing domain of wild-type BRAF and induced ubiquitination, followed by proteasome-dependent degradation, of the latter protein. Functionally, RNF149 attenuated the increase in cell growth induced by wild-type BRAF.

SIGNOR-272043

Q13131

Q8IWQ3

0

phosphorylation

up-regulates

0.291

Ampka1 activators increased phosphorylation level and cytoplasmic localization (reduced nuclear/cytoplasmic ratio). Ampka1 activators reduced rna synthesis in the nucleoli.

SIGNOR-176594