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
Q9Y4H2	P42336	2	binding	up-regulates activity	0.685	These results strongly suggest that the IGF2–IGF1R–IRS2 axis signals to PI3K in CRC and imply that therapeutic targeting of the pathway could act to block PI3K activity in this subset of patients.	SIGNOR-251492
Q14761	P68400	0	phosphorylation	up-regulates quantity by stabilization	0.2	We demonstrated for the first time that LPAP is a substrate for protein kinase CK2 that phosphorylates it at Ser153, presumably ensuring LPAP resistance to degradation.	SIGNOR-273629
P45983	P04150	1	phosphorylation	down-regulates	0.638	Taken together, these findings suggest that jnk-mediated phosphorylation of the gr-ser226 enhances gr nuclear export and may contribute to termination of gr-mediated transcription.	SIGNOR-93558
Q8TAT6	P55072	2	binding	up-regulates activity	0.946	These findings ascribe specific functions to each of the components of the VCP-UFD1L-NPL4 complex in Vpu-mediated CD4 degradation: VCP energizes the process through ATP binding and hydrolysis, UFD1L binds ubiquitinated CD4 through recognition of K48 Ub chains, and NPL4 stabilizes UFD1L. VCP is thus likely to provide the energy required for extraction of CD4 from membranes.	SIGNOR-252423
P43405	P15311	1	phosphorylation	up-regulates activity	0.447	Phospho-SYK has also been shown to specifically activate ezrin upon CD81 engagement.\|We found that the activated SYK led to a time dependent phosphorylation of ezrin (pY354 and pThr567) and radixin (pThr564) (XREF_FIG).	SIGNOR-279129
P17542	Q9UNE7	0	ubiquitination	down-regulates quantity by destabilization	0.356	Ubiquitination and degradation of Tal1/SCL are induced by notch signaling and depend on Skp2 and CHIP. CHIP promoted Tal1 degradation with both chaperone binding and ubiquitin ligase activities, which are mediated by its TPR domain and U box, respectively.	SIGNOR-271393
P31939	P50552	0	phosphorylation	up-regulates activity	0.342	ATIC and VASP phosphorylation is dependent on NPM-ALK kinase activity.	SIGNOR-276172
P29353	P00533	2	binding	up-regulates activity	0.913	Adaptors such as Shc, Grb2, Crk or the recently characterised Dok-R protein (Jones Dumont 1999) show a modular structure containing protein protein interaction domains and putative phosphorylation sites and act as signalling platforms which extend the receptors repertoire of activated intracellular pathways.	SIGNOR-107712
P42830	P25025	2	binding	up-regulates activity	0.752	CXCL5 is another ELR+ CXC chemokine and, thus, also potently attracts neutrophils. Just like CXCL1, CXCL5 also signals through CXCR2, explaining why, often, CXCL5 and CXCL1 are seen to function in parallel in PDAC. CXCL5 was increased in human pancreatic tissue compared to the normal pancreas, and the knockdown of CXCL5 in pancreatic cancer cell lines reduced the proliferation and migration ability of cells	SIGNOR-277730
P27361	O75581	1	phosphorylation	up-regulates	0.313	We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6.	SIGNOR-169004
Q92997	P49674	2	binding	up-regulates	0.669	Ckiepsilon was in a complex with axin and other downstream components of the wnt pathway, including dishevelled.	SIGNOR-71759
Q12800	P28482	0	phosphorylation	down-regulates	0.335	We previously established that phosphorylation of lsf in early g1 at ser-291 and ser-309 inhibits its transcriptional activity and that dephosphorylation later in g1 is required for its reactivation. At the peak activities of erk and cyclin c/cdk2 in early g1, lsf is efficiently phosphorylated on ser-291 and ser-309.	SIGNOR-184168
O94817	Q9H0Y0	2	binding	up-regulates	0.878	Analogous to ubiquitination, atg12 is conjugated to atg5 by atg7--an e1-like protein--and atg10--an e2-like protein.	SIGNOR-180129
Q02556	Q09161	2	binding	up-regulates activity	0.2	we found that tyrosine phosphorylated ICSBP activates CYBB and NCF2 transcription, during late myeloid differentiation, by interacting with PU.1, IRF1 and CBP.	SIGNOR-222939
Q9Y219	Q04721	2	binding	up-regulates	0.635	Binding of delta1, jagged1, and jagged2 to notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of notch2	SIGNOR-81367
P09651	P17252	0	phosphorylation	down-regulates	0.2	A survey of seven protein kinases showed that a1 was heavily phosphorylated by protein kinase c (pkc) and also was phosphorylated by casein kinase iiamino acid sequencing revealed that these sites were ser95, ser192, and ser199;phosphorylation at ser192 was more abundant than at ser95 and ser199. Phosphorylation by pkc inhibited the strand annealing activity of a1.	SIGNOR-32291
P32243	P14651	0	transcriptional regulation	up-regulates quantity by expression	0.2	Transactivation of the mouse OTX2 Luc constructs by the human HOXB1, HOXB2, and HOXB3 proteins. \| Likewise, the construct pOTX2LucΔ−710 showed an 8-, 12-, and 6-fold increase in transcriptional activity if co-transfected with pSG-HOXB1, -HOXB2, and -HOXB3, respectively	SIGNOR-261635
Q15797	P12757	2	binding	down-regulates	0.482	Ski also represses bmp signaling through interactions with smad4 and bmp-specific r-smads, smad1 or smad7	SIGNOR-195636
O00548	Q04721	2	binding	up-regulates	0.636	In this study, we demonstrate that dll1 can activate notch signaling mostly through notch2 receptor and can contribute to drug resistance to bortezomib, both in murine and human mm cells.	SIGNOR-199320
Q05397	P18031	0	dephosphorylation	down-regulates activity	0.346	The focal adhesion kinase (FAK) is a key regulator of cell migration. Phosphorylation at Tyr-397 activates FAK \|The dephosphorylation at Tyr-397 in FAK triggered by wild-type alpha-actinin and PTP 1B caused a significant increase in cell migration.	SIGNOR-248431
Q99626	O00330	2	binding	down-regulates activity	0.2	In the heterologous cell line BHK-21, Pdx1 inhibited by 60 to 80% the activation of the alpha-cell specific element G1 conferred by Pax-6 and/or Cdx-2/3. Although Pdx1 could bind three AT-rich motifs within G1, two of which are binding sites for Pax-6 and Cdx-2/3, the affinity of Pdx1 for G1 was much lower as compared to Pax-6. In addition, Pdx1 inhibited Pax-6 mediated activation through G3, to which Pdx1 was unable to bind. Moreover, a mutation impairing DNA binding of Pdx1 had no effect on its inhibition on Cdx-2/3. Since Pdx1 interacts directly with Pax-6 and Cdx-2/3 forming heterodimers, we suggest that Pdx1 inhibits glucagon gene transcription through protein to protein interactions with Pax-6 and Cdx-2/3.	SIGNOR-254904
P78347	P28482	0	phosphorylation	up-regulates	0.364	Tfii-i can be phosphorylated in vitro by erk and mutation of consensus map kinase substrate sites at serines 627 and 633 impairs the phosphorylation of tfii-i by erk and its activity on the c-fos promoter. These results suggest that erk regulates the activity of tfii-i by direct phosphorylation.	SIGNOR-74296
P30304	Q8NG66	0	phosphorylation	down-regulates	0.417	Nek11 regulates cdc25a degradation and the ir-induced g2/m checkpointincubation of wild-type cdc25a with nek11 led to a marked increase in phosphorylation of ser 82 and 88 as detected with the phosphospecific antibody recognizing these sites	SIGNOR-187867
Q03113	Q15722	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-257196
P42224	Q16539	0	phosphorylation	up-regulates activity	0.72	All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below).	SIGNOR-154779
Q14258	Q7Z434	1	polyubiquitination	down-regulates quantity by destabilization	0.77	We report here that RLR activation triggers MAVS ubiquitination on lysine 7 and 10 by the E3 ubiquitin ligase TRIM25 and marks it for proteasomal degradation concomitantly with downstream signaling.	SIGNOR-272042
Q8N4C8	Q15797	1	phosphorylation	down-regulates activity	0.2	Msn kinases directly phosphorylate α-helix 1 of Smad. we have identified Misshapen (Msn) and the mammalian orthologs TNIK, MINK1, and MAP4K4 as the kinases responsible for α-helix 1 phosphorylation.	SIGNOR-276336
P50542	O00623	0	ubiquitination	up-regulates activity	0.653	Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle.	SIGNOR-253020
P49190	Q96A98	2	binding	up-regulates	0.763	Subsequent efforts led to the isolation and definition of the primary structure of a novel peptide, referred to as tip39, from bovine hypothalamus and the synthetic peptide was shown to efficiently activate human, rat, and zebrafish pth2 receptors	SIGNOR-115124
Q9Y5U4	P28324	0	transcriptional regulation	up-regulates quantity by expression	0.2	Under these conditions, a significant reduction in INSIG2 expression was only observed when SAP1a siRNA was used. These observations provide supporting evidence that SAP1a may be one of the transactivators of the human INSIG2 promoter.	SIGNOR-261592
P18031	P00519	1	dephosphorylation	down-regulates	0.612	These results illustrate selectivity in the effects of ptps in a cellular context and suggest that ptp1b may function as a specific, negative regulator of p210 bcr-abl signalling in vivo.	SIGNOR-56815
P99999	P55211	2	binding	up-regulates activity	0.879	Caspase-9 and apaf-1 bind to each other via their respective nh2-terminal ced-3 homologous domains in the presence of cytochrome c and datp, an event that leads to caspase-9 activation.	SIGNOR-53585
Q8IX03	P51812	0	phosphorylation	up-regulates	0.2	Moreover, we found that rsk1/2 specifically phosphorylates kibra at two highly conserved sites (thr(929) and ser(947)) in vitro and in cells. Rsk-mediated phosphorylation is required for kibra binding to rsk1, but not rsk2.	SIGNOR-203302
Q14247	P29350	0	dephosphorylation	down-regulates activity	0.2	Shp1 interacts with cortactin and reduces cortactin phosphorylation at tyrosine 421; 3.\|induction of Shp1-cortactin complex formation impairs cortactin scaffolding-activity and negatively affects invadopodia behaviour; 4.	SIGNOR-277003
P52564	P53779	1	phosphorylation	up-regulates	0.464	A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subgroups of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase)	SIGNOR-45363
P27348	P48729	0	phosphorylation	down-regulates activity	0.516	This protein kinase has been identified as casein kinase Ialpha (CKIalpha) by peptide mapping analysis and sequencing. Among mammalian 14-3-3, only 14-3-3 tau possesses a phosphorylatable residue at the same position (Ser-233), and we show that this residue is also phosphorylated by CKI. In addition, we show that 14-3-3 zeta is exclusively phosphorylated on Thr-233 in human embryonic kidney 293 cells. The residue 233 is located within a region shown to be important for the association of 14-3-3 to target proteins.	SIGNOR-250795
Q16566	P56524	1	phosphorylation	down-regulates activity	0.62	CaMKIV phosphorylates HDAC4 in vitro and promotes its nuclear-cytoplasmic shuttling in vivo. \| Thus, CaMKIV can phosphorylate HDAC4 at Ser-467 and/or Ser-632 in vitro. \| Collectively, our results suggest that CaMKIV reverses the transcriptional repression activity of HDAC4 by stimulating the mobilization of HDAC4 out of the nucleus.	SIGNOR-250712
P69905	P15289	0	acetylation	up-regulates activity	0.2	ASA acetylates hemoglobin. Purified acetylated hemoglobin had a slightly increased oxygen affinity and decreased heme-heme interaction.	SIGNOR-251773
Q9Y314	P67775	1	ubiquitination	down-regulates quantity by destabilization	0.338	NOSIP mediates the monoubiquitination of the PP2A catalytic subunit and the loss of NOSIP results in an increase in PP2A activity in craniofacial tissue in NOSIP knockout mice.	SIGNOR-271498
Q14118	Q12955	0	relocalization	up-regulates quantity	0.259	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-266714
P30874	P15884	0	transcriptional regulation	up-regulates quantity by expression	0.358	Activation of somatostatin receptor II expression by transcription factors MIBP1 and SEF-2 in the murine brain.	SIGNOR-261618
Q92794	Q13950	2	binding	up-regulates	0.307	Moz and morf both interact with runx2 / while morf does not acetylate runx2, its sm domain potentiates runx2-dependent transcriptional activation.	SIGNOR-117332
P46531	Q8NFT8	2	binding	up-regulates	0.462	Dner binds to notch1 at cell-cell contacts and activates notch signaling in vitro.	SIGNOR-138346
P25098	P37840	1	phosphorylation	down-regulates activity	0.2	We found that grk-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and pld2. These findings suggest that gpcrs may be able to indirectly stimulate pld2 activity via their ability to regulate grk-promoted phosphorylation of synuclein.	SIGNOR-78333
O14733	P35568	1	phosphorylation	down-regulates activity	0.369	Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223 Ser312 can be phosphorylated by kinases, such as c-jun NH2-terminal kinase and inhibitor of _B kinase	SIGNOR-217920
Q92847	P08754	2	binding	up-regulates activity	0.373	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-257167
P31260	O43189	0	transcriptional regulation	down-regulates quantity by repression	0.285	These data support the proposed regulatory impact of particular PRC2-proteins in expression of HOXA9 and HOXA10 in NK/T-cells. In mammalian cells knockdown of PRC2 components EZH2 or PHF1 led to upregulated HOXA gene expression.	SIGNOR-260071
Q8N752	Q6ZRV2	2	binding	up-regulates quantity	0.2	We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.	SIGNOR-273755
P08754	Q5NUL3	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-257158
Q13501	P48729	0	phosphorylation	up-regulates activity	0.391	Mechanistically, CSNK1A1 interacted with STING1 upon the CGAS-STING1 pathway activation and promoted STING1 autophagic degradation by enhancing the phosphorylation of SQSTM1/p62 at serine 351 (serine 349 in human), which was critical for SQSTM1-mediated STING1 autophagic degradation.	SIGNOR-273769
P10415	P17252	0	phosphorylation	up-regulates	0.349	Purified pkca can efficiently and directly phosphorylate bcl2 at serine 70	SIGNOR-60120
Q02548	Q04727	2	binding	down-regulates activity	0.563	Grg4 efficiently represses the transcriptional activity of Pax5 in an octapeptide-dependent manner. Similar protein interactions resulting in transcriptional repression were also observed between distantly related members of both the Pax2/5/8 and Groucho protein families	SIGNOR-269083
P32239	P06307	2	binding	up-regulates	0.871	Cck8 interacts with nanomolar affinities with two different receptors designated cck-a and cck-b	SIGNOR-66339
O60271	Q16539	2	binding	up-regulates activity	0.561	Cdo, jlp, and p38alpha/beta form complexes in differentiating myoblasts, and cdo and jlp cooperate to enhance levels of active p38alpha/beta in transfectants.	SIGNOR-149979
P04040	Q16236	0	transcriptional regulation	up-regulates quantity by expression	0.426	BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2	SIGNOR-254651
P49759	P18031	1	phosphorylation	up-regulates activity	0.347	The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B. \| although CLK1 and CLK2 directly phosphorylate PTP-1B on both Ser50 and Ser242/Ser243, the preferred CLK phosphorylation site is Ser50, as it is preferentially phosphorylated at an approximate ratio of 9:1 over the Ser242/Ser243 site.	SIGNOR-250773
P49841	P17812	1	phosphorylation	down-regulates activity	0.2	We found that low serum conditions increased phosphorylation of endogenous CTPS1 and this phosphorylation was inhibited by the glycogen synthase kinase 3 (GSK3) inhibitor indirubin-3'-monoxime and GSK3beta short interfering RNAs, demonstrating the involvement of GSK3 in phosphorylation of endogenous human CTPS1. Separating tryptic peptides from [(32)P]orthophosphate-labeled cells and analyzing the phosphopeptides by mass spectrometry identified Ser-574 and Ser-575 as phosphorylated residues. Incubation with an alkaline phosphatase increased CTPS1 activity in a time-dependent manner, demonstrating that phosphorylation inhibits CTPS1 activity.	SIGNOR-276069
Q9NZV8	Q8N608	0	relocalization	up-regulates activity	0.533	Coexpression of DPP10 changes the subcellular localization of Kv4.2 expressed in COS-7 cells by promoting surface trafficking.DPP10 accelerates Kv4.2 inactivation at high and low voltages	SIGNOR-269006
O14640	P49674	0	phosphorylation	up-regulates activity	0.637	Phenotypic analysis of mutant mDvl-1 indicates that phosphorylation of these sites stimulates the Dvl-activated beta-catenin-dependent Wnt signaling pathway in both cell culture and in Xenopus development.	SIGNOR-217849
P05771	P62714	0	dephosphorylation	down-regulates activity	0.469	Specifically, the threonine at position 500 (T500) on the activation loop, and T641 and S660 on the carboxyl terminus of protein kinase C beta II are phosphorylated in vivo. T500 and S660 are selectively dephosphorylated in vitro by protein phosphatase 2A to yield an enzyme that is still capable of lipid-dependent activation, whereas all three residues are dephosphorylated by protein phosphatase 1 to yield an inactive enzyme.	SIGNOR-248585
P00533	Q96J02	0	polyubiquitination	down-regulates quantity by destabilization	0.48	In summary, we have shown that CBLC and AIP4 can interact and that these two E3 ligases could contribute to down-regulate EGFR signaling by ubiquitination.	SIGNOR-272604
P15498	P15391	2	binding	up-regulates activity	0.724	CD19 has an extracellular region containing two C2-type Ig-like domains and a cytoplasmic region of ~240 amino acids with 9 conserved tyrosine residues24. Lyn, a Src-family protein tyrosine kinase member, is the dominant kinase that phosphorylates CD19 upon stimulation. Once tyrosyl-phosphorylated, CD19 serves as a membrane-bound adaptor protein for Src homology 2-containing signaling molecules such as Lyn, Vav, and phosphatidylinositol 3-kinase, which further mediate downstream activation cascades.	SIGNOR-242897
Q08722	P35442	2	binding	up-regulates	0.592	We report here that iap is a receptor for the ts1 cbd and its vvm-containing peptides and that a function-blocking anti-iap mab inhibits the chemotactic response to ts1 and its cbd peptides in endothelial cells.	SIGNOR-39749
Q96QF0	P31749	0	phosphorylation	up-regulates activity	0.2	Rabin8 is phosphorylated and activated by Akt in cells grown on stiff ECM.	SIGNOR-277802
Q9Y6W5	P68400	0	phosphorylation	down-regulates	0.2	Here we identify five casein kinase 2 (ck2) phosphorylation sites within the vca domain of wave2, serines 482, 484, 488, 489, and 497. Phosphorylation of these sites is required for a high affinity interaction with the arp2/3 complex;we and show that their mutation to non-phosphorylatable alanine residues inhibits wave2 function in vivo.	SIGNOR-182350
P05129	P61764	1	phosphorylation	down-regulates activity	0.386	Munc18a is essential for neurotransmitter release by exocytosis and can be phosphorylated by PKC in vitro on Ser-306 and Ser-313. We demonstrate that it is phosphorylated on Ser-313 in response to phorbol ester treatment in adrenal chromaffin cells. Mutation of both phosphorylation sites to glutamate reduces its affinity for syntaxin and so acts as a phosphomimetic mutation.	SIGNOR-249187
P15056	Q13164	1	phosphorylation	up-regulates quantity	0.292	Our data indicate that oncogenic BRAF increases ERK5 protein level, phosphorylation at several residues and kinase activity.\|Overexpression of oncogenic BRAF induced ERK5 phosphorylation at Thr218 and Tyr220, although to a lower level than that induced by MEK5DD.	SIGNOR-278353
Q8NCW0	O94907	2	binding	up-regulates	0.605	Dkk1 has been shown to inhibitwnt by binding to and antagonizing lrp5/6. Here we show that the transmembrane proteins kremen1 and kremen2 are high-affinity dkk1 receptors that functionally cooperate with dkk1 to blockwnt/beta-catenin . Kremen2 forms a ternary complex with dkk1 and lrp6, and induces rapid endocytosis and removal of thewntreceptor lrp6 from the plasma membranekremen2 forms a ternary complex with dkk1 and lrp6, and induces rapid endocytosis and removal of the wnt receptor lrp6 from the plasma membrane	SIGNOR-88882
Q96F81	Q15465	2	binding	up-regulates activity	0.729	We show that the vertebrate homologue, dispatched-a (dispa) interacts with human sonic hedgehog (hshh) via its cholesterol anchor, and that this interaction is necessary for hshh secretion. binding to dispa is necessary but not sufficient for hshh secretion	SIGNOR-191888
O94992	P06748	2	binding	down-regulates activity	0.385	We identified NPM as a novel HEXIM1-binding protein. NPM functioned as a negative regulator of HEXIM1. cytoplasmic localization of endogenous HEXIM1 is detected in an acute myeloid leukemia (AML) cell line containing the NPMc+ mutation, suggesting the physiological importance of HEXIM1-NPMc+ interaction.	SIGNOR-260134
Q02447	P14210	1	transcriptional regulation	up-regulates quantity by expression	0.2	Furthermore, in transient cotransfection assays, overexpression of Sp1 and/or Sp3 stimulated HGF promoter activity independently and additively through binding to the Sp1 binding site in the HGF gene promoter region.	SIGNOR-251741
P22888	P49116	0	transcriptional regulation	up-regulates quantity by expression	0.2	Functional analysis showed that EAR2 and EAR3/COUP-TFI repressed the hLHR promoter activity, whereas TR4 activated hLHR gene transcription.	SIGNOR-266217
P45985	Q9Y6R4	0	phosphorylation	up-regulates activity	0.568	When truncated mapkkk4 (deltamapkkk4) was overexpressed in hek293 cells, it was constitutively activeco-expressed map kinase kinase (mkk)-1, mkk-4, mkk-3 and mkk-6 were activated in vivo by deltamapkkk4. All of the above mkks purified from escherichia coli were phosphorylated and activated by deltamapkkk4 immunoprecipitates in vitro.	SIGNOR-62369
Q6UUV7	P20749	2	binding	up-regulates	0.36	The ankyrin repeat domain of bcl3 interacted with torc3 / we determined that bcl3 inhibited transcription from the htlv-1 ltr in a manner dependent on torc3	SIGNOR-156950
O95835	O60285	0	phosphorylation	down-regulates	0.389	Moreover, we show that nuak1 phosphorylates lats1 at s464 and this has a role in controlling its stabilitycells that constitutively express nuak1 suffer gross aneuploidies and show diminished expression of the genomic stability regulator lats1	SIGNOR-161792
P19484	P11279	1	transcriptional regulation	up-regulates quantity by expression	0.441	Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy\|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1\|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants	SIGNOR-276555
P48047	P30405	2	binding	up-regulates activity	0.2	We here hypothesized that CypD phosphorylation on its residue S191 induces its translocation and binding to the OSCP to favor mPTP opening.	SIGNOR-264881
P21554	P09471	2	binding	up-regulates activity	0.464	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-257003
O60674	Q13651	0	phosphorylation	up-regulates activity	0.432	IL10R2 recruits cytoplasmic protein Jak1 followed by phosphorylation of tyrosine at position 705 in the STAT3 (705Y-STAT3) molecule. Phosphorylated STAT3 forms a homodimer, which is then translocated to the nucleus to facilitate transcriptional regulation of target genes.	SIGNOR-249545
P24941	O75688	0	dephosphorylation	down-regulates activity	0.362	CDK2 can be dephosphorylated and inactivated by protein phosphatase type 2C beta isoform long (PP2Cbetal), a unique phosphatase that was originally cloned from human liver.	SIGNOR-277153
P35568	Q8WWQ0	2	binding	up-regulates activity	0.512	We have recently reported the isolation of a PH domain-interacting protein, PHIP, which selectively binds to the IRS-1 PH domain and is stably associated with IRS-1 in mammalian cells. Here we demonstrate that overexpression of PHIP in fibroblasts enhances insulin-induced transcriptional responses in a mitogen-activated protein kinase-dependent manner.	SIGNOR-266962
P31751	O00327	1	phosphorylation	down-regulates activity	0.358	Consistent with mass spectrometry results, constitutive active Akt2 (Akt2-CA) induced wild-type (WT) Bmal1 protein phosphorylation, which was abolished by a serine to alanine mutation at Ser42 residue (S42A) but not a S422A/S513A double mutation, as shown by immunoblot assay with phospho-Akt substrate antiserum ( xref ).\|In line with the in vivo results, overexpression of Akt2-CA strikingly lowered Bmal1 protein abundance in the nucleus in primary hepatocytes (XREF_FIG and XREF_SUPPLEMENTARY).	SIGNOR-280177
P25024	Q00765	2	binding	up-regulates activity	0.324	In this study, we found that CXCR1 interacted with REEP5 and REEP6, but CXCR2 did not. Overexpression of REEP5 and REEP6 enhanced IL-8-stimulated cellular responses through CXCR1, whereas depletion of the proteins led to the downregulation of the responses.	SIGNOR-261366
P55055	P28702	2	binding	up-regulates	0.696	We provide genetic and molecular evidence that cholesterol homeostasis in scs does not require pparalpha and beta, but depends upon the tif2 coactivator and rxrbeta/lxrbeta heterodimers, in which rxrbeta af-2 is transcriptionally active.	SIGNOR-123094
O96013	P62826	1	phosphorylation	up-regulates	0.308	We show that ran is a substrate for p21-activated kinase 4 (pak4) and that its phosphorylation on serine-135 increases during mitosis.Altogether, our findings strongly suggest that pak4-mediated phosphorylation of gdp- or gtp-bound ran modulates the assembly of complexes that are required at specific subcellular localizations for ran to carry out its functions during mitotic progression.	SIGNOR-167667
Q06187	Q13422	1	phosphorylation	up-regulates activity	0.432	We demonstrate that BTK phosphorylates Ikaros at unique phosphorylation sites S214 and S215 in the close vicinity of its zinc finger 4 (ZF4) within the DNA binding domain, thereby augmenting its nuclear localization and sequence-specific DNA binding activity.	SIGNOR-279442
Q96PU5	Q96BR1	0	phosphorylation	down-regulates activity	0.445	Moreover, S422DSGK1, SGK1, and SGK3 also phosphorylated Nedd4-2 and thereby inhibited Nedd4-2 binding to its target.	SIGNOR-280125
P55087	P68400	0	phosphorylation	down-regulates activity	0.416	We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. AQP4 phosphorylation by CKII may thus provide a mechanism that regulates AQP4 cell surface expression. \| To determine whether Ser276 is an actual CKII substrate, we used GST–AQP4-Cter proteins in which only one out of the three C-terminal CKII consensus sites was sequentially conserved (Ser276, Ser285 and Ser315, respectively). Figure 7B (right panel) shows that the three serine residues, including Ser276, were indeed efficiently phosphorylated by CKII.	SIGNOR-250827
Q13536	P01100	1	transcriptional regulation	up-regulates quantity by expression	0.2	CROC-4: a novel brain specific transcriptional activator of c-fos expressed from proliferation through to maturation of multiple neuronal cell types.	SIGNOR-261569
Q9GZV5	P48730	0	phosphorylation	down-regulates	0.366	LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP)	SIGNOR-234438
O95999	Q9Y6K9	2	binding	up-regulates	0.827	Here, we show that bcl10 undergoes k63-linked polyubiquitination in response to t cell activation and subsequently binds nemo, the regulatory subunit of ikk.	SIGNOR-160967
P16157	O00533	0	relocalization	up-regulates quantity	0.532	Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.	SIGNOR-266724
P49841	Q04206	1	phosphorylation	up-regulates	0.357	Rela is phosphorylated at: ser276 by the catalytic subunit of protein kinase a (pkac), msk1 and msk2; at ser311 by the atypical pkczeta; at ser468 by ikkbeta, ikkepsilon and glycogen-synthase kinase-3beta (gsk3beta); at ser529 by ck2; and at ser536 by ikkbeta, ikkalfa, ikkepsilon, nf-kb activating kinase (nak, also known as tank-binding kinase-1 tbk1)) and rsk1 (also known as p90 ribosomal protein s6 kinase (p90s6k) .	SIGNOR-151422
P55085	P24158	0	cleavage	down-regulates activity	0.373	PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases \| The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II\|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.\|Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3	SIGNOR-263601
Q9NTG7	P48735	1	deacetylation	up-regulates	0.657	Site-specific, genetic incorporation of n(_)-acetyllysine into position 413 of idh2 revealed that acetylated idh2 displays a dramatic 44-fold loss in activity. Deacetylation by sirt3 fully restored maximum idh2 activity.	SIGNOR-196617
P26583	P14859	2	binding	up-regulates activity	0.307	HMG2 and Oct2 interact via their HMG domains and POU homeodomains, respectively. This interaction is not restricted to Oct2, as other members of the octamer transcription factor family like Oct1 and Oct6 also interact with HMG2. The interaction with HMG2 results in a marked increase in the sequence-specific DNA binding activity of the Oct proteins	SIGNOR-240151
Q9UBN7	P00533	0	phosphorylation	down-regulates	0.44	A negative feedback loop consisting of egfr-mediated phosphorylation of hdac6 tyr(570) resulted in reduced deacetylase activity and increased acetylation of alpha-tubulin.	SIGNOR-162431
O94925	P05412	0	transcriptional regulation	up-regulates quantity by expression	0.35	The transcription factor c-Jun can directly bind to the GLS gene promoter and enhance expression	SIGNOR-268035
Q96SN8	Q76N32	0	relocalization	up-regulates activity	0.452	We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. \|Retention of Cep68 or PCNT in late mitosis prevents the removal of Cep215	SIGNOR-275624
P19086	Q9UNW8	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-257275

Q9Y4H2

P42336

2

binding

up-regulates activity

0.685

These results strongly suggest that the IGF2–IGF1R–IRS2 axis signals to PI3K in CRC and imply that therapeutic targeting of the pathway could act to block PI3K activity in this subset of patients.

SIGNOR-251492

Q14761

P68400

0

phosphorylation

up-regulates quantity by stabilization

0.2

We demonstrated for the first time that LPAP is a substrate for protein kinase CK2 that phosphorylates it at Ser153, presumably ensuring LPAP resistance to degradation.

SIGNOR-273629

P45983

P04150

1

phosphorylation

down-regulates

0.638

Taken together, these findings suggest that jnk-mediated phosphorylation of the gr-ser226 enhances gr nuclear export and may contribute to termination of gr-mediated transcription.

SIGNOR-93558

Q8TAT6

P55072

2

binding

up-regulates activity

0.946

These findings ascribe specific functions to each of the components of the VCP-UFD1L-NPL4 complex in Vpu-mediated CD4 degradation: VCP energizes the process through ATP binding and hydrolysis, UFD1L binds ubiquitinated CD4 through recognition of K48 Ub chains, and NPL4 stabilizes UFD1L. VCP is thus likely to provide the energy required for extraction of CD4 from membranes.

SIGNOR-252423

P43405

P15311

1

phosphorylation

up-regulates activity

0.447

Phospho-SYK has also been shown to specifically activate ezrin upon CD81 engagement.|We found that the activated SYK led to a time dependent phosphorylation of ezrin (pY354 and pThr567) and radixin (pThr564) (XREF_FIG).

SIGNOR-279129

P17542

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.356

Ubiquitination and degradation of Tal1/SCL are induced by notch signaling and depend on Skp2 and CHIP. CHIP promoted Tal1 degradation with both chaperone binding and ubiquitin ligase activities, which are mediated by its TPR domain and U box, respectively.

SIGNOR-271393

P31939

P50552

0

phosphorylation

up-regulates activity

0.342

ATIC and VASP phosphorylation is dependent on NPM-ALK kinase activity.

SIGNOR-276172

P29353

P00533

2

binding

up-regulates activity

0.913

Adaptors such as Shc, Grb2, Crk or the recently characterised Dok-R protein (Jones Dumont 1999) show a modular structure containing protein protein interaction domains and putative phosphorylation sites and act as signalling platforms which extend the receptors repertoire of activated intracellular pathways.

SIGNOR-107712

P42830

P25025

2

binding

up-regulates activity

0.752

CXCL5 is another ELR+ CXC chemokine and, thus, also potently attracts neutrophils. Just like CXCL1, CXCL5 also signals through CXCR2, explaining why, often, CXCL5 and CXCL1 are seen to function in parallel in PDAC. CXCL5 was increased in human pancreatic tissue compared to the normal pancreas, and the knockdown of CXCL5 in pancreatic cancer cell lines reduced the proliferation and migration ability of cells

SIGNOR-277730

P27361

O75581

1

phosphorylation

up-regulates

0.313

We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6.

SIGNOR-169004

Q92997

P49674

2

binding

up-regulates

0.669

Ckiepsilon was in a complex with axin and other downstream components of the wnt pathway, including dishevelled.

SIGNOR-71759

Q12800

P28482

0

phosphorylation

down-regulates

0.335

We previously established that phosphorylation of lsf in early g1 at ser-291 and ser-309 inhibits its transcriptional activity and that dephosphorylation later in g1 is required for its reactivation. At the peak activities of erk and cyclin c/cdk2 in early g1, lsf is efficiently phosphorylated on ser-291 and ser-309.

SIGNOR-184168

O94817

Q9H0Y0

2

binding

up-regulates

0.878

Analogous to ubiquitination, atg12 is conjugated to atg5 by atg7--an e1-like protein--and atg10--an e2-like protein.

SIGNOR-180129

Q02556

Q09161

2

binding

up-regulates activity

0.2

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

SIGNOR-222939

Q9Y219

Q04721

2

binding

up-regulates

0.635

Binding of delta1, jagged1, and jagged2 to notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of notch2

SIGNOR-81367

P09651

P17252

0

phosphorylation

down-regulates

0.2

A survey of seven protein kinases showed that a1 was heavily phosphorylated by protein kinase c (pkc) and also was phosphorylated by casein kinase iiamino acid sequencing revealed that these sites were ser95, ser192, and ser199;phosphorylation at ser192 was more abundant than at ser95 and ser199. Phosphorylation by pkc inhibited the strand annealing activity of a1.

SIGNOR-32291

P32243

P14651

0

transcriptional regulation

up-regulates quantity by expression

0.2

Transactivation of the mouse OTX2 Luc constructs by the human HOXB1, HOXB2, and HOXB3 proteins. | Likewise, the construct pOTX2LucΔ−710 showed an 8-, 12-, and 6-fold increase in transcriptional activity if co-transfected with pSG-HOXB1, -HOXB2, and -HOXB3, respectively

SIGNOR-261635

Q15797

P12757

2

binding

down-regulates

0.482

Ski also represses bmp signaling through interactions with smad4 and bmp-specific r-smads, smad1 or smad7

SIGNOR-195636

O00548

Q04721

2

binding

up-regulates

0.636

In this study, we demonstrate that dll1 can activate notch signaling mostly through notch2 receptor and can contribute to drug resistance to bortezomib, both in murine and human mm cells.

SIGNOR-199320

Q05397

P18031

0

dephosphorylation

down-regulates activity

0.346

The focal adhesion kinase (FAK) is a key regulator of cell migration. Phosphorylation at Tyr-397 activates FAK |The dephosphorylation at Tyr-397 in FAK triggered by wild-type alpha-actinin and PTP 1B caused a significant increase in cell migration.

SIGNOR-248431

Q99626

O00330

2

binding

down-regulates activity

0.2

In the heterologous cell line BHK-21, Pdx1 inhibited by 60 to 80% the activation of the alpha-cell specific element G1 conferred by Pax-6 and/or Cdx-2/3. Although Pdx1 could bind three AT-rich motifs within G1, two of which are binding sites for Pax-6 and Cdx-2/3, the affinity of Pdx1 for G1 was much lower as compared to Pax-6. In addition, Pdx1 inhibited Pax-6 mediated activation through G3, to which Pdx1 was unable to bind. Moreover, a mutation impairing DNA binding of Pdx1 had no effect on its inhibition on Cdx-2/3. Since Pdx1 interacts directly with Pax-6 and Cdx-2/3 forming heterodimers, we suggest that Pdx1 inhibits glucagon gene transcription through protein to protein interactions with Pax-6 and Cdx-2/3.

SIGNOR-254904

P78347

P28482

0

phosphorylation

up-regulates

0.364

Tfii-i can be phosphorylated in vitro by erk and mutation of consensus map kinase substrate sites at serines 627 and 633 impairs the phosphorylation of tfii-i by erk and its activity on the c-fos promoter. These results suggest that erk regulates the activity of tfii-i by direct phosphorylation.

SIGNOR-74296

P30304

Q8NG66

0

phosphorylation

down-regulates

0.417

Nek11 regulates cdc25a degradation and the ir-induced g2/m checkpointincubation of wild-type cdc25a with nek11 led to a marked increase in phosphorylation of ser 82 and 88 as detected with the phosphospecific antibody recognizing these sites

SIGNOR-187867

Q03113

Q15722

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-257196

P42224

Q16539

0

phosphorylation

up-regulates activity

0.72

All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below).

SIGNOR-154779

Q14258

Q7Z434

1

polyubiquitination

down-regulates quantity by destabilization

0.77

We report here that RLR activation triggers MAVS ubiquitination on lysine 7 and 10 by the E3 ubiquitin ligase TRIM25 and marks it for proteasomal degradation concomitantly with downstream signaling.

SIGNOR-272042

Q8N4C8

Q15797

1

phosphorylation

down-regulates activity

0.2

Msn kinases directly phosphorylate α-helix 1 of Smad. we have identified Misshapen (Msn) and the mammalian orthologs TNIK, MINK1, and MAP4K4 as the kinases responsible for α-helix 1 phosphorylation.

SIGNOR-276336

P50542

O00623

0

ubiquitination

up-regulates activity

0.653

Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle.

SIGNOR-253020

P49190

Q96A98

2

binding

up-regulates

0.763

Subsequent efforts led to the isolation and definition of the primary structure of a novel peptide, referred to as tip39, from bovine hypothalamus and the synthetic peptide was shown to efficiently activate human, rat, and zebrafish pth2 receptors

SIGNOR-115124

Q9Y5U4

P28324

0

transcriptional regulation

up-regulates quantity by expression

0.2

Under these conditions, a significant reduction in INSIG2 expression was only observed when SAP1a siRNA was used. These observations provide supporting evidence that SAP1a may be one of the transactivators of the human INSIG2 promoter.

SIGNOR-261592

P18031

P00519

1

dephosphorylation

down-regulates

0.612

These results illustrate selectivity in the effects of ptps in a cellular context and suggest that ptp1b may function as a specific, negative regulator of p210 bcr-abl signalling in vivo.

SIGNOR-56815

P99999

P55211

2

binding

up-regulates activity

0.879

Caspase-9 and apaf-1 bind to each other via their respective nh2-terminal ced-3 homologous domains in the presence of cytochrome c and datp, an event that leads to caspase-9 activation.

SIGNOR-53585

Q8IX03

P51812

0

phosphorylation

up-regulates

0.2

Moreover, we found that rsk1/2 specifically phosphorylates kibra at two highly conserved sites (thr(929) and ser(947)) in vitro and in cells. Rsk-mediated phosphorylation is required for kibra binding to rsk1, but not rsk2.

SIGNOR-203302

Q14247

P29350

0

dephosphorylation

down-regulates activity

0.2

Shp1 interacts with cortactin and reduces cortactin phosphorylation at tyrosine 421; 3.|induction of Shp1-cortactin complex formation impairs cortactin scaffolding-activity and negatively affects invadopodia behaviour; 4.

SIGNOR-277003

P52564

P53779

1

phosphorylation

up-regulates

0.464

A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subgroups of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase)

SIGNOR-45363

P27348

P48729

0

phosphorylation

down-regulates activity

0.516

This protein kinase has been identified as casein kinase Ialpha (CKIalpha) by peptide mapping analysis and sequencing. Among mammalian 14-3-3, only 14-3-3 tau possesses a phosphorylatable residue at the same position (Ser-233), and we show that this residue is also phosphorylated by CKI. In addition, we show that 14-3-3 zeta is exclusively phosphorylated on Thr-233 in human embryonic kidney 293 cells. The residue 233 is located within a region shown to be important for the association of 14-3-3 to target proteins.

SIGNOR-250795

Q16566

P56524

1

phosphorylation

down-regulates activity

0.62

CaMKIV phosphorylates HDAC4 in vitro and promotes its nuclear-cytoplasmic shuttling in vivo. | Thus, CaMKIV can phosphorylate HDAC4 at Ser-467 and/or Ser-632 in vitro. | Collectively, our results suggest that CaMKIV reverses the transcriptional repression activity of HDAC4 by stimulating the mobilization of HDAC4 out of the nucleus.

SIGNOR-250712

P69905

P15289

0

acetylation

up-regulates activity

0.2

ASA acetylates hemoglobin. Purified acetylated hemoglobin had a slightly increased oxygen affinity and decreased heme-heme interaction.

SIGNOR-251773

Q9Y314

P67775

1

ubiquitination

down-regulates quantity by destabilization

0.338

NOSIP mediates the monoubiquitination of the PP2A catalytic subunit and the loss of NOSIP results in an increase in PP2A activity in craniofacial tissue in NOSIP knockout mice.

SIGNOR-271498

Q14118

Q12955

0

relocalization

up-regulates quantity

0.259

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-266714

P30874

P15884

0

transcriptional regulation

up-regulates quantity by expression

0.358

Activation of somatostatin receptor II expression by transcription factors MIBP1 and SEF-2 in the murine brain.

SIGNOR-261618

Q92794

Q13950

2

binding

up-regulates

0.307

Moz and morf both interact with runx2 / while morf does not acetylate runx2, its sm domain potentiates runx2-dependent transcriptional activation.

SIGNOR-117332

P46531

Q8NFT8

2

binding

up-regulates

0.462

Dner binds to notch1 at cell-cell contacts and activates notch signaling in vitro.

SIGNOR-138346

P25098

P37840

1

phosphorylation

down-regulates activity

0.2

We found that grk-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and pld2. These findings suggest that gpcrs may be able to indirectly stimulate pld2 activity via their ability to regulate grk-promoted phosphorylation of synuclein.

SIGNOR-78333

O14733

P35568

1

phosphorylation

down-regulates activity

0.369

Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223 Ser312 can be phosphorylated by kinases, such as c-jun NH2-terminal kinase and inhibitor of _B kinase

SIGNOR-217920

Q92847

P08754

2

binding

up-regulates activity

0.373

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-257167

P31260

O43189

0

transcriptional regulation

down-regulates quantity by repression

0.285

These data support the proposed regulatory impact of particular PRC2-proteins in expression of HOXA9 and HOXA10 in NK/T-cells. In mammalian cells knockdown of PRC2 components EZH2 or PHF1 led to upregulated HOXA gene expression.

SIGNOR-260071

Q8N752

Q6ZRV2

2

binding

up-regulates quantity

0.2

We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.

SIGNOR-273755

P08754

Q5NUL3

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-257158

Q13501

P48729

0

phosphorylation

up-regulates activity

0.391

Mechanistically, CSNK1A1 interacted with STING1 upon the CGAS-STING1 pathway activation and promoted STING1 autophagic degradation by enhancing the phosphorylation of SQSTM1/p62 at serine 351 (serine 349 in human), which was critical for SQSTM1-mediated STING1 autophagic degradation.

SIGNOR-273769

P10415

P17252

0

phosphorylation

up-regulates

0.349

Purified pkca can efficiently and directly phosphorylate bcl2 at serine 70

SIGNOR-60120

Q02548

Q04727

2

binding

down-regulates activity

0.563

Grg4 efficiently represses the transcriptional activity of Pax5 in an octapeptide-dependent manner. Similar protein interactions resulting in transcriptional repression were also observed between distantly related members of both the Pax2/5/8 and Groucho protein families

SIGNOR-269083

P32239

P06307

2

binding

up-regulates

0.871

Cck8 interacts with nanomolar affinities with two different receptors designated cck-a and cck-b

SIGNOR-66339

O60271

Q16539

2

binding

up-regulates activity

0.561

Cdo, jlp, and p38alpha/beta form complexes in differentiating myoblasts, and cdo and jlp cooperate to enhance levels of active p38alpha/beta in transfectants.

SIGNOR-149979

P04040

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.426

BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2

SIGNOR-254651

P49759

P18031

1

phosphorylation

up-regulates activity

0.347

The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B. | although CLK1 and CLK2 directly phosphorylate PTP-1B on both Ser50 and Ser242/Ser243, the preferred CLK phosphorylation site is Ser50, as it is preferentially phosphorylated at an approximate ratio of 9:1 over the Ser242/Ser243 site.

SIGNOR-250773

P49841

P17812

1

phosphorylation

down-regulates activity

0.2

We found that low serum conditions increased phosphorylation of endogenous CTPS1 and this phosphorylation was inhibited by the glycogen synthase kinase 3 (GSK3) inhibitor indirubin-3'-monoxime and GSK3beta short interfering RNAs, demonstrating the involvement of GSK3 in phosphorylation of endogenous human CTPS1. Separating tryptic peptides from [(32)P]orthophosphate-labeled cells and analyzing the phosphopeptides by mass spectrometry identified Ser-574 and Ser-575 as phosphorylated residues. Incubation with an alkaline phosphatase increased CTPS1 activity in a time-dependent manner, demonstrating that phosphorylation inhibits CTPS1 activity.

SIGNOR-276069

Q9NZV8

Q8N608

0

relocalization

up-regulates activity

0.533

Coexpression of DPP10 changes the subcellular localization of Kv4.2 expressed in COS-7 cells by promoting surface trafficking.DPP10 accelerates Kv4.2 inactivation at high and low voltages

SIGNOR-269006

O14640

P49674

0

phosphorylation

up-regulates activity

0.637

Phenotypic analysis of mutant mDvl-1 indicates that phosphorylation of these sites stimulates the Dvl-activated beta-catenin-dependent Wnt signaling pathway in both cell culture and in Xenopus development.

SIGNOR-217849

P05771

P62714

0

dephosphorylation

down-regulates activity

0.469

Specifically, the threonine at position 500 (T500) on the activation loop, and T641 and S660 on the carboxyl terminus of protein kinase C beta II are phosphorylated in vivo. T500 and S660 are selectively dephosphorylated in vitro by protein phosphatase 2A to yield an enzyme that is still capable of lipid-dependent activation, whereas all three residues are dephosphorylated by protein phosphatase 1 to yield an inactive enzyme.

SIGNOR-248585

P00533

Q96J02

0

polyubiquitination

down-regulates quantity by destabilization

0.48

In summary, we have shown that CBLC and AIP4 can interact and that these two E3 ligases could contribute to down-regulate EGFR signaling by ubiquitination.

SIGNOR-272604

P15498

P15391

2

binding

up-regulates activity

0.724

CD19 has an extracellular region containing two C2-type Ig-like domains and a cytoplasmic region of ~240 amino acids with 9 conserved tyrosine residues24. Lyn, a Src-family protein tyrosine kinase member, is the dominant kinase that phosphorylates CD19 upon stimulation. Once tyrosyl-phosphorylated, CD19 serves as a membrane-bound adaptor protein for Src homology 2-containing signaling molecules such as Lyn, Vav, and phosphatidylinositol 3-kinase, which further mediate downstream activation cascades.

SIGNOR-242897

Q08722

P35442

2

binding

up-regulates

0.592

We report here that iap is a receptor for the ts1 cbd and its vvm-containing peptides and that a function-blocking anti-iap mab inhibits the chemotactic response to ts1 and its cbd peptides in endothelial cells.

SIGNOR-39749

Q96QF0

P31749

0

phosphorylation

up-regulates activity

0.2

Rabin8 is phosphorylated and activated by Akt in cells grown on stiff ECM.

SIGNOR-277802

Q9Y6W5

P68400

0

phosphorylation

down-regulates

0.2

Here we identify five casein kinase 2 (ck2) phosphorylation sites within the vca domain of wave2, serines 482, 484, 488, 489, and 497. Phosphorylation of these sites is required for a high affinity interaction with the arp2/3 complex;we and show that their mutation to non-phosphorylatable alanine residues inhibits wave2 function in vivo.

SIGNOR-182350

P05129

P61764

1

phosphorylation

down-regulates activity

0.386

Munc18a is essential for neurotransmitter release by exocytosis and can be phosphorylated by PKC in vitro on Ser-306 and Ser-313. We demonstrate that it is phosphorylated on Ser-313 in response to phorbol ester treatment in adrenal chromaffin cells. Mutation of both phosphorylation sites to glutamate reduces its affinity for syntaxin and so acts as a phosphomimetic mutation.

SIGNOR-249187

P15056

Q13164

1

phosphorylation

up-regulates quantity

0.292

Our data indicate that oncogenic BRAF increases ERK5 protein level, phosphorylation at several residues and kinase activity.|Overexpression of oncogenic BRAF induced ERK5 phosphorylation at Thr218 and Tyr220, although to a lower level than that induced by MEK5DD.

SIGNOR-278353

Q8NCW0

O94907

2

binding

up-regulates

0.605

Dkk1 has been shown to inhibitwnt by binding to and antagonizing lrp5/6. Here we show that the transmembrane proteins kremen1 and kremen2 are high-affinity dkk1 receptors that functionally cooperate with dkk1 to blockwnt/beta-catenin . Kremen2 forms a ternary complex with dkk1 and lrp6, and induces rapid endocytosis and removal of thewntreceptor lrp6 from the plasma membranekremen2 forms a ternary complex with dkk1 and lrp6, and induces rapid endocytosis and removal of the wnt receptor lrp6 from the plasma membrane

SIGNOR-88882

Q96F81

Q15465

2

binding

up-regulates activity

0.729

We show that the vertebrate homologue, dispatched-a (dispa) interacts with human sonic hedgehog (hshh) via its cholesterol anchor, and that this interaction is necessary for hshh secretion. binding to dispa is necessary but not sufficient for hshh secretion

SIGNOR-191888

O94992

P06748

2

binding

down-regulates activity

0.385

We identified NPM as a novel HEXIM1-binding protein. NPM functioned as a negative regulator of HEXIM1. cytoplasmic localization of endogenous HEXIM1 is detected in an acute myeloid leukemia (AML) cell line containing the NPMc+ mutation, suggesting the physiological importance of HEXIM1-NPMc+ interaction.

SIGNOR-260134

Q02447

P14210

1

transcriptional regulation

up-regulates quantity by expression

0.2

Furthermore, in transient cotransfection assays, overexpression of Sp1 and/or Sp3 stimulated HGF promoter activity independently and additively through binding to the Sp1 binding site in the HGF gene promoter region.

SIGNOR-251741

P22888

P49116

0

transcriptional regulation

up-regulates quantity by expression

0.2

Functional analysis showed that EAR2 and EAR3/COUP-TFI repressed the hLHR promoter activity, whereas TR4 activated hLHR gene transcription.

SIGNOR-266217

P45985

Q9Y6R4

0

phosphorylation

up-regulates activity

0.568

When truncated mapkkk4 (deltamapkkk4) was overexpressed in hek293 cells, it was constitutively activeco-expressed map kinase kinase (mkk)-1, mkk-4, mkk-3 and mkk-6 were activated in vivo by deltamapkkk4. All of the above mkks purified from escherichia coli were phosphorylated and activated by deltamapkkk4 immunoprecipitates in vitro.

SIGNOR-62369

Q6UUV7

P20749

2

binding

up-regulates

0.36

The ankyrin repeat domain of bcl3 interacted with torc3 / we determined that bcl3 inhibited transcription from the htlv-1 ltr in a manner dependent on torc3

SIGNOR-156950

O95835

O60285

0

phosphorylation

down-regulates

0.389

Moreover, we show that nuak1 phosphorylates lats1 at s464 and this has a role in controlling its stabilitycells that constitutively express nuak1 suffer gross aneuploidies and show diminished expression of the genomic stability regulator lats1

SIGNOR-161792

P19484

P11279

1

transcriptional regulation

up-regulates quantity by expression

0.441

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

SIGNOR-276555

P48047

P30405

2

binding

up-regulates activity

0.2

We here hypothesized that CypD phosphorylation on its residue S191 induces its translocation and binding to the OSCP to favor mPTP opening.

SIGNOR-264881

P21554

P09471

2

binding

up-regulates activity

0.464

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-257003

O60674

Q13651

0

phosphorylation

up-regulates activity

0.432

IL10R2 recruits cytoplasmic protein Jak1 followed by phosphorylation of tyrosine at position 705 in the STAT3 (705Y-STAT3) molecule. Phosphorylated STAT3 forms a homodimer, which is then translocated to the nucleus to facilitate transcriptional regulation of target genes.

SIGNOR-249545

P24941

O75688

0

dephosphorylation

down-regulates activity

0.362

CDK2 can be dephosphorylated and inactivated by protein phosphatase type 2C beta isoform long (PP2Cbetal), a unique phosphatase that was originally cloned from human liver.

SIGNOR-277153

P35568

Q8WWQ0

2

binding

up-regulates activity

0.512

We have recently reported the isolation of a PH domain-interacting protein, PHIP, which selectively binds to the IRS-1 PH domain and is stably associated with IRS-1 in mammalian cells. Here we demonstrate that overexpression of PHIP in fibroblasts enhances insulin-induced transcriptional responses in a mitogen-activated protein kinase-dependent manner.

SIGNOR-266962

P31751

O00327

1

phosphorylation

down-regulates activity

0.358

Consistent with mass spectrometry results, constitutive active Akt2 (Akt2-CA) induced wild-type (WT) Bmal1 protein phosphorylation, which was abolished by a serine to alanine mutation at Ser42 residue (S42A) but not a S422A/S513A double mutation, as shown by immunoblot assay with phospho-Akt substrate antiserum ( xref ).|In line with the in vivo results, overexpression of Akt2-CA strikingly lowered Bmal1 protein abundance in the nucleus in primary hepatocytes (XREF_FIG and XREF_SUPPLEMENTARY).

SIGNOR-280177

P25024

Q00765

2

binding

up-regulates activity

0.324

In this study, we found that CXCR1 interacted with REEP5 and REEP6, but CXCR2 did not. Overexpression of REEP5 and REEP6 enhanced IL-8-stimulated cellular responses through CXCR1, whereas depletion of the proteins led to the downregulation of the responses.

SIGNOR-261366

P55055

P28702

2

binding

up-regulates

0.696

We provide genetic and molecular evidence that cholesterol homeostasis in scs does not require pparalpha and beta, but depends upon the tif2 coactivator and rxrbeta/lxrbeta heterodimers, in which rxrbeta af-2 is transcriptionally active.

SIGNOR-123094

O96013

P62826

1

phosphorylation

up-regulates

0.308

We show that ran is a substrate for p21-activated kinase 4 (pak4) and that its phosphorylation on serine-135 increases during mitosis.Altogether, our findings strongly suggest that pak4-mediated phosphorylation of gdp- or gtp-bound ran modulates the assembly of complexes that are required at specific subcellular localizations for ran to carry out its functions during mitotic progression.

SIGNOR-167667

Q06187

Q13422

1

phosphorylation

up-regulates activity

0.432

We demonstrate that BTK phosphorylates Ikaros at unique phosphorylation sites S214 and S215 in the close vicinity of its zinc finger 4 (ZF4) within the DNA binding domain, thereby augmenting its nuclear localization and sequence-specific DNA binding activity.

SIGNOR-279442

Q96PU5

Q96BR1

0

phosphorylation

down-regulates activity

0.445

Moreover, S422DSGK1, SGK1, and SGK3 also phosphorylated Nedd4-2 and thereby inhibited Nedd4-2 binding to its target.

SIGNOR-280125

P55087

P68400

0

phosphorylation

down-regulates activity

0.416

We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. AQP4 phosphorylation by CKII may thus provide a mechanism that regulates AQP4 cell surface expression. | To determine whether Ser276 is an actual CKII substrate, we used GST–AQP4-Cter proteins in which only one out of the three C-terminal CKII consensus sites was sequentially conserved (Ser276, Ser285 and Ser315, respectively). Figure 7B (right panel) shows that the three serine residues, including Ser276, were indeed efficiently phosphorylated by CKII.

SIGNOR-250827

Q13536

P01100

1

transcriptional regulation

up-regulates quantity by expression

0.2

CROC-4: a novel brain specific transcriptional activator of c-fos expressed from proliferation through to maturation of multiple neuronal cell types.

SIGNOR-261569

Q9GZV5

P48730

0

phosphorylation

down-regulates

0.366

LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP)

SIGNOR-234438

O95999

Q9Y6K9

2

binding

up-regulates

0.827

Here, we show that bcl10 undergoes k63-linked polyubiquitination in response to t cell activation and subsequently binds nemo, the regulatory subunit of ikk.

SIGNOR-160967

P16157

O00533

0

relocalization

up-regulates quantity

0.532

Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.

SIGNOR-266724

P49841

Q04206

1

phosphorylation

up-regulates

0.357

Rela is phosphorylated at: ser276 by the catalytic subunit of protein kinase a (pkac), msk1 and msk2; at ser311 by the atypical pkczeta; at ser468 by ikkbeta, ikkepsilon and glycogen-synthase kinase-3beta (gsk3beta); at ser529 by ck2; and at ser536 by ikkbeta, ikkalfa, ikkepsilon, nf-kb activating kinase (nak, also known as tank-binding kinase-1 tbk1)) and rsk1 (also known as p90 ribosomal protein s6 kinase (p90s6k) .

SIGNOR-151422

P55085

P24158

0

cleavage

down-regulates activity

0.373

PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3

SIGNOR-263601

Q9NTG7

P48735

1

deacetylation

up-regulates

0.657

Site-specific, genetic incorporation of n(_)-acetyllysine into position 413 of idh2 revealed that acetylated idh2 displays a dramatic 44-fold loss in activity. Deacetylation by sirt3 fully restored maximum idh2 activity.

SIGNOR-196617

P26583

P14859

2

binding

up-regulates activity

0.307

HMG2 and Oct2 interact via their HMG domains and POU homeodomains, respectively. This interaction is not restricted to Oct2, as other members of the octamer transcription factor family like Oct1 and Oct6 also interact with HMG2. The interaction with HMG2 results in a marked increase in the sequence-specific DNA binding activity of the Oct proteins

SIGNOR-240151

Q9UBN7

P00533

0

phosphorylation

down-regulates

0.44

A negative feedback loop consisting of egfr-mediated phosphorylation of hdac6 tyr(570) resulted in reduced deacetylase activity and increased acetylation of alpha-tubulin.

SIGNOR-162431

O94925

P05412

0

transcriptional regulation

up-regulates quantity by expression

0.35

The transcription factor c-Jun can directly bind to the GLS gene promoter and enhance expression

SIGNOR-268035

Q96SN8

Q76N32

0

relocalization

up-regulates activity

0.452

We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. |Retention of Cep68 or PCNT in late mitosis prevents the removal of Cep215

SIGNOR-275624

P19086

Q9UNW8

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-257275