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
Q99836	Q9NWZ3	2	binding	up-regulates activity	0.946	Signaling between MyD88 and TRAF6 is mediated by members of the IL-1R-associated kinase (IRAK) family; however, the exact function of each IRAK protein remains controversial. IRAK-1 is required for the optimal transduction of IL-1R- and TLR-mediated signals, but IRAK-1 can be replaced by other IRAKs. Surprisingly, gene targeting studies show that the newest IRAK protein, IRAK-4, has an essential role in mediating signals initiated by IL-1R and TLR engagement.	SIGNOR-252097
Q15438	P06241	0	phosphorylation	up-regulates activity	0.394	Fyn directly binds, phosphorylates, and activates cytohesin-1.	SIGNOR-280015
O14543	Q9Y286	2	binding	down-regulates quantity by destabilization	0.372	SOCS proteins can act as E3 ligases by forming a complex with Elongin B/C and Cul5/Rbx1/2.SOCS3 targets Siglec 7 for degradation	SIGNOR-272642
P46527	Q9UBF6	0	ubiquitination	down-regulates activity	0.348	SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.	SIGNOR-271447
P49137	Q00613	1	phosphorylation	down-regulates activity	0.519	A potential mechanism for MK2-induced HSF1 inactivation is suggested by the findings that phosphorylation of serine 121 enhances HSF1 binding to HSP90, a major repressor of HSF1.\|Phosphorylation of HSF1 by MAPK activated protein kinase 2 on serine 121, inhibits transcriptional activity and promotes HSP90 binding.	SIGNOR-279541
P63000	Q05397	0	phosphorylation	up-regulates activity	0.574	Both Src and FAK phosphorylate Rac1 at tyrosine 64.\|Our investigations of direct interactions between Rac1, Src, and FAK were motivated by our previous insights into FAK augmentation of Rac1 activation during cell spreading, and the Cerione lab 's work on the interactions between Src and Cdc42 , .	SIGNOR-279652
P61244	P50539	2	binding	up-regulates activity	0.558	The role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences.	SIGNOR-240314
P48740	O75636	2	binding	up-regulates activity	0.672	H-ficolin binds to PSA, a polysaccharide produced by Aerococcus viridans. C4 was activated by H-ficolin preparations bound to PSA which had been coated on ELISA plates. These results indicate that H-ficolin is a second ficolin which is associated with MASPs and sMAP, and which activates the lectin pathway\|Proteolytic activation of complement components by H-ficolin-MASP.	SIGNOR-263410
O00470	P35452	2	binding	up-regulates activity	0.422	We now show that the Hoxa-9 protein physically interacts with Meis1 proteins. Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.	SIGNOR-241232
P28482	Q05682	1	phosphorylation	down-regulates	0.539	Extracellular signal-regulated kinases (erks) phosphorylate the high molecular mass isoform of the actin-binding protein caldesmon (h-cad) at two sites (ser(759) and ser(789)) during smooth muscle stimulation. Nmr spectroscopy shows that the actin binding properties of the minimal inhibitory region of caldesmon, residues 750-779, alter upon map kinase phosphorylation of ser-759, a residue not involved in actin binding. This phosphorylation leads to markedly diminished actin affinity as a result of the loss of interaction at one of the two sites that bind to f-actin.	SIGNOR-71037
P00738	P68871	2	binding	down-regulates quantity	0.774	Haptoglobin forms a complex of extremely high affinity with Hb via a well-characterized globin site. Our results show that upon Hb-haptoglobin binding, the globin radical, loses its ability to be terminated by forming globin dimers.	SIGNOR-251815
Q9UPC5	P63096	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-256688
Q96RL1	P38398	2	binding	up-regulates	0.91	Rap80 specifically recruits brca1 to dna damage sites and functions with brca1 in g2/m checkpoint control	SIGNOR-155201
P19544	Q05066	2	binding	up-regulates	0.2	Here we report that wt1 binds to and acts synergistically with sry to activate transcription from a promoter containing sry-binding sites	SIGNOR-100345
O60858	P04234	1	polyubiquitination	down-regulates quantity by destabilization	0.2	RFP2, a gene frequently lost in various malignancies, encodes a protein with RING finger, B-box, and coiled-coil domains that belongs to the RBCC/TRIM family of proteins.Rfp2 Regulates the Stability of the ERAD Substrate CD3-δ. In summary, these experiments demonstrate that Rfp2 functions as a RING-dependent ERAD E3 ubiquitin ligase and regulates the degradation of the ER substrate, CD3-δ.	SIGNOR-271644
O43312	P08151	2	binding	up-regulates	0.543	Mim is a shh-responsive gene that can potentiate gli transcriptional activity.MIM Appears to regulate target gene expression through its association with the gli complex	SIGNOR-157650
P10242	P09488	1	transcriptional regulation	up-regulates quantity by expression	0.2	Functional analysis of the GSTM1 promoter using reporter assays indicated that both the DNA binding and transactivation domains of Myb were required for transcriptional activation	SIGNOR-253975
P33981	P27816	1	phosphorylation	down-regulates quantity by destabilization	0.2	We further uncovered that Mps1 is a kinase of MAP4, and E7-MAP4 binding blocks Mps1 phosphorylation of MAP4, thereby interrupting phosphorylation-dependent MAP4 degradation.	SIGNOR-277458
P41594	P05771	0	phosphorylation	up-regulates activity	0.354	Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.	SIGNOR-249286
P63092	P29275	2	binding	up-regulates activity	0.516	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256767
P84022	P78368	0	phosphorylation	down-regulates	0.337	Cki?2 Directly phosphorylates smad3 at ser418, leading to the increased ubiquitination and proteasomal degradation of activated smad3 following tgf-? Treatment.	SIGNOR-181069
Q9Y4D8	Q8TEK3	0	transcriptional regulation	down-regulates quantity by repression	0.2	Overexpression of DOT1L decreased the expression of HECTD4 and MYCBP2 in LNCaP, C42B, and 22rv1 cells (Supplementary Fig. 5c), suggesting that DOT1L plays a role in repressing these targets either directly or indirectly.	SIGNOR-267150
P60484	Q15831	0	phosphorylation	down-regulates activity	0.604	The C-terminal tail of PTEN is also the target of mutations in tumors. As mentioned, this region contains the main phosphorylation sites mapped to residues Ser362, Thr366, Ser370, Ser380, Thr382, Thr383, and Ser385, and the kinases involved are casein kinase 2 (CK2), GSK3_, LKB1, and MAST.84,97-101 The phosphorylation of the tail has been shown to enhance PTEN stability but at the same time decrease its phosphatase activity	SIGNOR-161118
Q00535	Q99958	1	phosphorylation	up-regulates activity	0.35	Cdk5 phosphorylates Foxc2 and activates Foxc2 dependent transcription.	SIGNOR-279156
Q9HBA0	P17252	0	phosphorylation	up-regulates activity	0.38	We conclude that the serine/threonine kinases PKC and PKA enhance activation of the TRPV4 ion channel by phosphorylation at specific sites and that phosphorylation depends on assembly of PKC and PKA by AKAP79 into a signaling complex with TRPV4.	SIGNOR-260882
P10415	Q16611	2	binding	down-regulates	0.677	Bcl-2 bind to bax or five other pro-apoptotic relatives (bak, bad, bik, bid or bim)	SIGNOR-55546
Q5MNZ9	Q676U5	2	binding	up-regulates quantity	0.606	WIPI1 assists WIPI2 in recruiting ATG16L for LC3 lipidation. WIPI1-WIPI2 heterodimer may function more efficiently in ATG16L complex recruitment.	SIGNOR-268477
P46937	P31947	0	relocalization	down-regulates activity	0.461	Verteporfin increases the level of 14-3-3σ, which promotes the translocation of YAP from nucleus to cytoplasm.	SIGNOR-278130
P35247	P17676	0	transcriptional regulation	up-regulates quantity by expression	0.251	Cotransfection of C/EBPalpha, C/EBPbeta, or C/EBPdelta cDNA in H441 lung adenocarcinoma cells significantly increased the luciferase activity of a wild-type SP-D promoter construct containing 698 bp of upstream sequence (SS698). Transfection of C/EBP also increased the level of endogenous SP-D mRNA in H441 cells\| Thus, interactions among C/EBP elements in the near-distal promoter can modulate the promoter activity of SP-D.	SIGNOR-254045
Q96GD4	P68431	1	phosphorylation	down-regulates activity	0.2	Histone code pathway involving h3 s28 phosphorylation and k27 acetylation activates transcription and antagonizes polycomb silencingaurora-b phosphorylates histone h3 at serine28 with regard to the mitotic chromosome condensation	SIGNOR-171717
P04637	Q05655	0	phosphorylation	up-regulates	0.677	Here, we show that the pro-apoptotic kinase, protein kinase c delta (pkcdelta), is involved in phosphorylation of p53 on ser(46). pkcdelta potentiates p53-dependent apoptosis by ser(46) phosphorylation in response to genotoxic stress.	SIGNOR-143382
P04637	P12931	0	phosphorylation	down-regulates quantity by destabilization	0.524	We recently found that ISGylation of the p53 tumor suppressor is an important novel mechanism to control its stability. Here we identified that Isg15-dependent regulation of p53 can be enhanced by different oncogenes. We further show that the Src-mediated phosphorylation of p53 on Tyr126 and Tyr220 has a positive effect on p53 ISGylation by enhancing Herc5 binding.	SIGNOR-276668
P27361	O75030	1	phosphorylation	down-regulates quantity by destabilization	0.542	More interestingly, ERK-dependent phosphorylation of MITF at Ser 73 is essential for MITF ubiquitinilation and degradation (87). Putting together all these findings, it can be proposed that MAPK activation inhibits melanogenesis due to an increased MITF degradation which is dependent on the MAPK-induced MITF phosphorylation and ubiquitinilation. In summary, although the phosphorylation of MITF at Ser73 increases its intrinsic transcriptional activity, this phosphorylation also targets MITF to the proteasome for its degradation. Consequently, the decrease in MITF levels leads to a down-regulation of melanogenic enzymes expression and to an inhibition of melanogenesis.	SIGNOR-249620
Q9BXM7	O43318	1	phosphorylation	up-regulates activity	0.33	PINK1 also enhances the association between TRAF6 and TAK1, phosphorylates TAK1, and stimulates polyubiquitination of TAK1.	SIGNOR-279644
Q8IXQ5	Q9H6E5	2	binding	down-regulates quantity by destabilization	0.2	Kelch-like protein 7 (KLHL7) is a component of Cul3-based Cullin-RING ubiquitin ligase. In this study, we report that KLHL7 increases terminal uridylyl transferase 1 (TUT1) ubiquitination involved in nucleolar integrity.	SIGNOR-272318
Q14934	P51812	0	phosphorylation	up-regulates	0.385	The results indicated that rsk2 phosphorylated two additional sites at ser289 (peptide 2) and ser344 (peptide 3)rsk2 induced nuclear localization of nfat3. Rsk2 phosphorylated nfat3 in vitro (km=3.559 microm), and activation of nfat3 by rsk2 enhanced the promoter activity of nfat3 downstream target genes in vivo.	SIGNOR-234473
Q08209	Q9NZJ5	0	phosphorylation	down-regulates activity	0.2	CN becomes phosphorylated by PERK, decreasing its activity.\|Finally, evidence is presented that PERK phosphorylates CN-A at low resting levels of Ca 2+.	SIGNOR-278933
Q13309	P10244	1	polyubiquitination	down-regulates quantity by destabilization	0.378	P19Skp1 and Cul-1 bind to the F-box protein p45Skp2 to form a complex (SCF) that functions as E3 ubiquitin ligase.We show that B-Myb physically and functionally interacts with components of the Cdc34-SCFp45Skp2 ubiquitin pathway and propose that B-Myb degradation may be required for controlling the correct alternation of events during progression through the cell division cycle.	SIGNOR-272572
P25025	P14174	2	binding	up-regulates activity	0.382	We identify the chemokine receptors CXCR2 and CXCR4 as functional receptors for MIF [] By activating both CXCR2 and CXCR4, MIF displays chemokine-like functions and acts as a major regulator of inflammatory cell recruitment and atherogenesis.	SIGNOR-252061
P17252	P43629	1	phosphorylation	down-regulates activity	0.2	Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of Ser(394) by protein kinase C slightly suppresses KIR3DL1 inhibitory function, and reduces receptor internalization and turnover.Both CKII and PKC phosphorylate KIR3DL1 in vitro. Ser364 can be phosphorylated after phosphorylation of Ser367 by CKII.	SIGNOR-276080
P10828	P23769	2	binding	down-regulates activity	0.2	We found that the T3-bound TR inhibits this reporter construct driven by GATA2 alone, indicating that the target of T3-bound TR repression is GATA2.	SIGNOR-267256
O15344	Q13153	0	phosphorylation	up-regulates activity	0.2	Pak1 phosphorylates the N-terminus of Mid1 to promote its association with cortical nodes.\|Pak1 promotes Mid1 localization to cortical nodes.	SIGNOR-279307
Q13555	Q15746	1	phosphorylation	down-regulates activity	0.331	Phosphorylation of MLC kinase by CaM protein kinase II increased the dissociation constant of MLC kinase for calmodulin about 10 times without changing the Vmax. The location of the phosphorylation sites was identified by isolating and sequencing the tryptic phosphopeptides of MLC kinase. The preferred site was identified as serine 512 and the second site as serine 525. These sites are the same as the sites phosphorylated by cAMP-dependent protein kinase.	SIGNOR-250700
Q9H2X6	Q9UK99	2	binding	down-regulates quantity by destabilization	0.404	O clarify the role of PML in transcription regulation, we purified the PML complex and identified Fbxo3 (Fbx3), Skp1, and Cullin1 as novel components of this complex. Fbx3 formed SCF(Fbx3) ubiquitin ligase and promoted the degradation of HIPK2 and p300 by the ubiquitin-proteasome pathway.	SIGNOR-271741
P06493	P38398	1	phosphorylation	up-regulates	0.497	However, shrna-mediated depletion of cdk1 alone or small molecule cdk1 inhibition abrogated s phase cell-cycle arrest and the phosphorylation of a subset of atr/atm targets after dna damage. Loss of dna damage-induced checkpoint control was caused by a reduction in formation of brca1-containing foci. Mutation of brca1 at s1497 and s1189/s1191 resulted in loss of cdk1-mediated phosphorylation and also compromised formation of brca1-containing foci.	SIGNOR-72087
Q16584	P45985	1	phosphorylation	up-regulates	0.625	These data suggest that mlk-3 phosphorylates sek1 directly and that it does so specifically on those residues known to activate sek1 in vivo.	SIGNOR-75836
O14559	P06241	0	phosphorylation	down-regulates	0.461	Tcgap interacted with fyn and was phosphorylated by fyn, with tyr-406 in the gap domain as a major fyn-mediated phosphorylation site. Fyn suppressed the gap activity of wild-type tcgap	SIGNOR-147156
P50406	Q00535	0	phosphorylation	down-regulates activity	0.374	Cdk5 phosphorylates the 5-HT6R on serine 350 (Ser350)\|This suggests that the 5-HT6R is unable to interact with GPRIN1 when it is phosphorylated by Cdk5.	SIGNOR-264407
P35222	Q9NQU5	0	phosphorylation	down-regulates quantity	0.2	Moreover, we find that \u03b2-catenin is also localized with PAK6 in cell-cell junctions and is a novel PAK6 substrate.\|PAK6 binds to and phosphorylates beta-catenin.	SIGNOR-279546
Q16206	Q05655	0	phosphorylation	up-regulates	0.2	Tnox is phosphorylated by protein kinase c_ (pkc_) both in vitro and in vivo. Replacement of serine-504 with alanine significantly reduces phosphorylation by pkc_. C. overexpression of the s504a tnox mutant leads to diminished cell proliferation and migration, reflecting reduced stability of the unphosphorylatable tnox mutant protein.	SIGNOR-197706
Q9GZV5	Q99594	2	binding	up-regulates	0.699	When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead14.	SIGNOR-201415
Q14344	P50406	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-257443
P40189	O14543	2	binding	down-regulates activity	0.652	SOCS3 binds specific receptor-JAK complexes to control cytokine signaling by direct kinase inhibition. The inhibitory protein SOCS3 plays a key part in the immune and hematopoietic systems by regulating signaling induced by specific cytokines. SOCS3 functions by inhibiting the catalytic activity of Janus kinases (JAKs) that initiate signaling within the cell.	SIGNOR-255328
O60462	Q99985	2	binding	up-regulates	0.585	Our experiments establish that small peptides containing the consensus decd sequence of sperm fertilinbeta bind specifically to an alpha6beta1 integrin receptor on the egg membrane. We conclude that fertilinbeta binds directly to the alpha6beta1 integrin on the egg surface and this partnership mediates sperm-egg fusion.	SIGNOR-147564
Q92997	P31431	2	binding	up-regulates	0.247	Like other wnt co-receptors, syndecan 4 directly interacts with dvl during pcp 1.	SIGNOR-199638
P16885	P43405	0	phosphorylation	up-regulates activity	0.753	Syk in turn phosphorylates and activates the B cell linker protein (BLNK), phosphoinositide 3-kinase (PI3K) and phospholipase C\u03b32 (PLC\u03b32).\|Syk in turn phosphorylates and activates the B cell linker protein (BLNK), phosphoinositide 3-kinase (PI3K) and phospholipase Cgamma2 (PLCgamma2).	SIGNOR-278995
P28482	P49841	1	phosphorylation	down-regulates activity	0.383	We demonstrate that insulin-mediated activation of ERK1/2 results in phosphorylation of GSK3β at S9 independently of Akt/mTORC1 activity in Tsc2 null mouse embryonic fibroblasts. In addition, we show that inhibition of ERK1/2 rescues GSK3β activity and restores protein synthesis in Tsc2 −/− MEFs to normal levels	SIGNOR-262524
P35968	Q12913	0	dephosphorylation	down-regulates	0.699	The autoactivation residues y1054 and y1059 are targeted by dep-1 and this results in the inhibition of kinase activity and the consequent general dephosphorylation of vegfr2.	SIGNOR-181672
O15530	P05129	1	phosphorylation	up-regulates	0.2	One of the most studiedevents controlled by ptdins(3,4,5)p3, comprises the activation of aof agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum- and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated.	SIGNOR-126072
Q9Y5X1	P50570	2	binding	up-regulates	0.812	Snx9 binds directly to bothdynamin-1 anddynamin-2. Moreover by stimulatingdynaminassembly, snx9 stimulatesdynamin's basal gtpase activity and potentiates assembly-stimulated gtpase activity on liposomes.	SIGNOR-133976
P63092	O15169	2	binding	up-regulates	0.381	We show that pge2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (g protein) coupled receptor, ep2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase akt by free g protein bg subunits and the direct association of the g protein as subunit with the regulator of g protein signaling (rgs) domain of axin.	SIGNOR-141789
Q12772	P04035	1	transcriptional regulation	up-regulates quantity by expression	0.492	The processed SREBP2, designated nuclear SREBP2 (nSREBP2), then enters the nucleus as a homodimer, binds to the sterol regulatory element (SRE) sequence in the promoters of target genes, including HMGCR and SQLE (encoding squalene monooxygenase), and upregulates their transcription	SIGNOR-265161
P28482	Q9UPP1	1	phosphorylation	down-regulates activity	0.2	Upon IFNgamma treatment, PHF8 is phosphorylated by ERK2 and evicted from the promoters, which correlates with an increase in H4K20me1 and H3K4me3 levels.	SIGNOR-279745
Q7Z6Z7	P20226	1	ubiquitination	down-regulates quantity	0.337	Having established that Huwe1 mediates TBP ubiquitination in vitro, we then asked which E2 conjugating enzymes work best with Huwe1 in this reaction.\|Upregulation of Huwe1 expression during myogenesis induces TBP degradation and myotube differentiation.	SIGNOR-278696
Q16236	P04179	1	transcriptional regulation	up-regulates quantity by expression	0.45	BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2	SIGNOR-254652
Q99990	P51812	0	phosphorylation	down-regulates activity	0.2	Site-directed mutagenesis and immunoprecipitation experiments revealed that RSK2 phosphorylated VGLL1 at S84 in the presence of TGF-β. Mutation of VGLL1 at S84 suppressed VGLL1-TEAD4 binding and the subsequent transcriptional activation of matrix metalloprotease 9 (MMP9).	SIGNOR-273842
P19525	P40763	1	phosphorylation	up-regulates activity	0.612	Silencing PKR gene expression in HepG2 cells with siRNA reduced STAT3 phosphorylation at Tyr705 and Ser727 (XREF_FIG).\|The results also revealed that PKR activates STAT3, a transcription factor associated with primary liver tumors, which is suggested to promote tumor cell proliferation.	SIGNOR-279613
P06493	Q9BW19	1	phosphorylation	up-regulates quantity by stabilization	0.458	We confirmed that CDK1 phosphorylates Ser6 (Supplementary Fig S5B) and demonstrated that KIFC1 displays CDK1-mediated resistance to ubiquitination by the APC/C (Fig S5C).	SIGNOR-277294
P38398	Q13363	0	transcriptional regulation	down-regulates quantity by repression	0.603	Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor with oncogenic potential. We found CtBP1 was recruited to the promoter regions of Brca1 and E-cadherin genes in breast cancer cells.	SIGNOR-259196
Q8NEV9	Q6UWB1	2	binding	up-regulates	0.711	Wsx-1 and glycoprotein 130 constitute a signal-transducing receptor for il-27.	SIGNOR-121799
Q9Y448	Q8N4N8	1	relocalization	down-regulates activity	0.407	The protein astrin has been shown to remove Kif2b from kinetochores in metaphase through competitive binding of CLASP1 (Manning et al., 2010 blue right-pointing triangle). During prometaphase, Aurora B kinase activity prevents astrin from localizing to kinetochores (Manning et al., 2010 blue right-pointing triangle; Schmidt et al., 2010 blue right-pointing triangle). This permits Kif2b to localize to kinetochores to destabilize k-MT attachments to execute error correction through Plk1-dependent recruitment and activation.	SIGNOR-252053
O43852	P38435	2	binding	down-regulates activity	0.401	Results are presented that demonstrate that the endoplasmic reticulum chaperone protein calumenin is associated with gamma-carboxylase and inhibits its activity.	SIGNOR-265910
Q13618	Q9Y4X5	2	binding	up-regulates activity	0.314	Here, we provide evidence that Ariadne RBR E3 ubiquitin ligases such as TRIAD1 and HHARI can bind and be activated by CRL complexes. Whereas TRIAD1 specifically associates with CUL5–RBX2, HHARI is more promiscuous towards cullin types and associates with RBX1-associated cullins 1, 2, 3, and 4A. Interestingly, both TRIAD1 and HHARI show a strong preference for binding the neddylated form of the cullin. Our data suggest a novel function of NEDD8 in directing specific CRLs to Ariadne RBR ligases, which in turn exert influence on the levels of their cognate neddylated cullin.	SIGNOR-268846
P07339	P05067	1	cleavage	down-regulates quantity by destabilization	0.489	The precise cathepsin D cleavage sites within these recombinant betaAPP substrates were identified using this technique. Both recombinant substrates were cleaved at the following sites: Leu49-Val50, Asp68-Ala69, Phe93-Phe94. \| two additional cleavage sites near the amino terminus of betaA4, Glu-3-Val-2 and Glu3-Phe4, were observed, indicating that cathepsin D cleavage of betaAPP is influenced by the structural integrity of the substrate. Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism.	SIGNOR-261767
P19174	Q9UJZ1	2	binding	up-regulates activity	0.2	In these studies, we also found that SLP-2 interacted with Lck, ZAP70, LAT, and PLC-gamma1 during the 30-min period following stimulation in vitro\|The SLP-2-associated pool of these molecules became phosphorylated/activated in a sequential manner, a profile compatible with their temporal involvement in early TCR signalling.	SIGNOR-260378
O14746	P12931	0	phosphorylation	down-regulates	0.418	Hydrogen peroxide triggers nuclear export of telomerase reverse transcriptase via src kinase family-dependent phosphorylation of tyrosine 707	SIGNOR-102097
Q16659	P06493	0	phosphorylation	up-regulates	0.484	Using ms analysis, we identified four novel phosphorylation sites, ser684, ser688, thr698 and ser705, located at the extreme c-terminus of erk3. All four sites are followed by a proline residue. We have shown that purified cyclin b-cdk1 (cyclindependent kinase 1) phosphorylates these sitesalanine substitution of the four c-terminal phosphorylation sites markedly decreased the half-life of erk3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase.	SIGNOR-164499
O76074	O94844	2	binding	down-regulates quantity by destabilization	0.2	RhoBTB1 augmented the cGMP response to nitric oxide by restraining the activity of phosphodiesterase 5 (PDE5) by acting as a substrate adaptor delivering PDE5 to the Cullin-3 E3 Ring ubiquitin ligase complex for ubiquitination inhibiting PDE5.	SIGNOR-272312
Q9UPN4	P49137	0	phosphorylation	down-regulates quantity	0.291	We identify CEP131 as a major Centriolar satellites-associated substrate of p38-dependent, MK2-mediated phosphorylation on two defined residues and show that these modifications promote binding to 14-3-3 proteins, in turn leading to cytoplasmic sequestration of CEP131 and associated Centriolar satellites factors.\|We therefore conclude that MK2 dependent phosphorylation of CEP131 at S47 and S78 and the ensuing binding of 14-3-3 proteins play an essential role in triggering stress induced remodelling of CS.	SIGNOR-278181
Q9Y6D9	P12270	2	binding	up-regulates	0.486	Tpr directly binds to mad1 and mad2. / depletion of tpr decreases the levels of mad1 at kinetochores during prometaphase, correlating with the inability of mad1 to activate mad2, which is required for inhibiting apc(cdc20).	SIGNOR-181918
P46020	Q16816	2	binding	down-regulates activity	0.691	Phk is among the most complex of the protein kinases so far elucidated. It has one catalytic (gamma) subunit and three different regulatory (alpha, beta, and delta) subunits, a molecular mass of 1.3 X 106 daltons, and each holoenzyme molecule is presumed to contain four molecules of each subunit. The three regulatory subunits inhibit the phosphotransferase activity of the gamma subunit.	SIGNOR-267405
Q99250	P68400	0	phosphorylation	up-regulates activity	0.2	We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. \| inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G.	SIGNOR-275761
P46527	P12931	0	phosphorylation	down-regulates	0.496	Src regulates p27 stability through phosphorylation of p27 at tyrosine 74 and tyrosine 88. Our data indicate that phosphorylation by src impairs the cdk2 inhibitory action of p27	SIGNOR-152839
Q13158	P25445	2	binding	up-regulates activity	0.91	Aggregation-induced conformational changes in fas lead to the formation of the death-inducing signalling complex (disc) which involves recruitment of the adaptor protein fadd/mort1 through a homotypic interaction of death domains, present in both the intracellular region of fas and the c-terminus of fadd.	SIGNOR-176651
P49116	P22888	1	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
P31749	Q13882	0	phosphorylation	up-regulates	0.476	Here we demonstrate that AKT is a direct substrate of PTK6 and that AKT tyrosine residues 315 and 326 are phosphorylated by PTK6.	SIGNOR-252622
Q05513	Q8N2W9	1	phosphorylation	down-regulates quantity by destabilization	0.519	In this study, we discovered a new protein isoform encoded by KIAA0317, termed fibrosis-inducing E3 ligase 1 (FIEL1), which potently stimulates the TGFbeta signaling pathway through the site-specific ubiquitination of PIAS4.FIEL1 targets PIAS4 using a double locking mechanism that is facilitated by the kinases PKCzeta and GSK3beta. Specifically, PKCzeta phosphorylation of PIAS4 and GSK3beta phosphorylation of FIEL1 are both essential for the degradation of PIAS4.\|These experiments suggested that PKCzeta is an authentic regulator of PIAS4 protein stability; Q21 and phosphorylated S18 of PIAS4 are both required for FIEL1 interaction.	SIGNOR-275513
Q9UMX1	P08151	2	binding	down-regulates activity	0.949	Here we characterize structural and functional determinants of Su(fu) required for Gli regulation and show that Su(fu) contains at least two distinct domains: a highly conserved carboxy-terminal region required for binding to the amino-terminal ends of the Gli proteins and a unique amino-terminal domain that binds the carboxy-terminal tail of Gli1. While each domain is capable of binding to different Gli1 regions independently, interactions between Su(fu) and Gli1 at both sites are required for cytoplasmic tethering and repression of Gli1	SIGNOR-249591
Q9P2R6	Q07812	1	relocalization	up-regulates activity	0.2	We detected RERE protein mainly in the nucleus, where it colocalizes with the promyelocytic leukemia protein in promyelocytic leukemia oncogenic domains (PODs). Overexpression of RERE recruits a fraction of the proapoptotic protein BAX to PODS: This observation correlates with RERE-induced apoptosis, which occurs in a caspase-dependent manner.	SIGNOR-264485
Q00535	P16220	1	phosphorylation	up-regulates activity	0.374	CDK5 Activates the Self-Renewal Regulator CREB1 in GSCs.\|Our data indicate that CDK5, which has previously been shown to activate CREB1 through cAMP and PKA in dopamine neurons present in the ventral tegmental area, can directly bind with and phosphorylate CREB1 in a PKA and cAMP independent manner, at least in GSCs.	SIGNOR-279682
P35658	Q13485	2	binding	up-regulates	0.561	We demonstrate that smad3 and smad4 are capable of interaction with the nucleoporin can/nup214, and this interaction is required for nuclear import	SIGNOR-117647
P10082	P50391	2	binding	up-regulates	0.669	Human y4 bound human pp family members in i-pyy membrane binding assays with a distinctive rank order (table 1): pp > pyy > npy > npy free acid.	SIGNOR-29767
Q14524	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-253418
Q06187	P05771	0	phosphorylation	down-regulates activity	0.382	We provide direct evidence that PKCbeta acts as a feedback loop inhibitor of Btk activation. Inhibition of PKCbeta results in a dramatic increase in B-cell receptor (BCR)-mediated Ca2+ signaling. We identified a highly conserved PKCbeta serine phosphorylation site in a short linker within the Tec homology domain of Btk. Mutation of this phosphorylation site led to enhanced tyrosine phosphorylation and membrane association of Btk, and augmented BCR and FcepsilonRI-mediated signaling in B and mast cells, respectively. \| This deductive analysis indicated that PKCbeta phosphorylates S180 in the region bisecting the Btk motif (BM) and the PRR of the TH domain.	SIGNOR-249110
Q96T60	P78527	0	phosphorylation	up-regulates	0.649	We demonstrate that pnkp is phosphorylated by the dna-dependent protein kinase (dna-pk) and ataxia-telangiectasia mutated (atm) in vitro. The major phosphorylation site for both kinases was serine 114, with serine 126 being a minor site. Purified pnkp protein with mutation of serines 114 and 126 had decreased dna kinase and dna phosphatase activities and reduced affinity for dna in vitro.	SIGNOR-176020
Q7Z6J0	Q02779	2	binding	up-regulates	0.355	Taken together, these findings support a model in which apoptotic stimuli or posh overexpression induce direct association between posh and inactive mlks.	SIGNOR-97003
Q6ZMT4	Q16665	0	transcriptional regulation	up-regulates quantity by expression	0.2	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271572
P11802	P19532	1	phosphorylation	up-regulates activity	0.2	CDK4 and CDK6 interact with TFEB and TFE3 in the nucleus We next investigated how CDK4 and CDK6 activate TFEB and TFE3 .\|We found that CDK4 and CDK6 interact with and phosphorylate nuclear TFEB and TFE3, thereby promoting their shuttling to the cytoplasm.	SIGNOR-279514
P27540	Q16665	2	binding	up-regulates activity	0.787	The functional transcription factor exists as a heterodimeric complex consisting of HIF-1alpha and the aryl hydrocarbon receptor nuclear translocator (ARNT). Association of HIF-1 with ARNT is required for its activity; however, no other role has been ascribed to this interaction.	SIGNOR-253720
P28482	Q96EP5	1	phosphorylation	down-regulates activity	0.2	Further experiments showed that DAZAP1 was phosphorylated stoichiometrically in vitro by ERK2 (extracellular-signal-regulated protein kinase 2) at two Thr-Pro sequences (Thr269 and Thr315), and that both sites became phosphorylated in HEK-293 (human embryonic kidney 293) cells in response to PMA or EGF (epidermal growth factor), or RAW 264.7 macrophages in response to LPS. Phosphorylation of the ARE-binding protein DAZAP1 by ERK2 induces its dissociation from DAZ	SIGNOR-262970

Q99836

Q9NWZ3

2

binding

up-regulates activity

0.946

Signaling between MyD88 and TRAF6 is mediated by members of the IL-1R-associated kinase (IRAK) family; however, the exact function of each IRAK protein remains controversial. IRAK-1 is required for the optimal transduction of IL-1R- and TLR-mediated signals, but IRAK-1 can be replaced by other IRAKs. Surprisingly, gene targeting studies show that the newest IRAK protein, IRAK-4, has an essential role in mediating signals initiated by IL-1R and TLR engagement.

SIGNOR-252097

Q15438

P06241

0

phosphorylation

up-regulates activity

0.394

Fyn directly binds, phosphorylates, and activates cytohesin-1.

SIGNOR-280015

O14543

Q9Y286

2

binding

down-regulates quantity by destabilization

0.372

SOCS proteins can act as E3 ligases by forming a complex with Elongin B/C and Cul5/Rbx1/2.SOCS3 targets Siglec 7 for degradation

SIGNOR-272642

P46527

Q9UBF6

0

ubiquitination

down-regulates activity

0.348

SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.

SIGNOR-271447

P49137

Q00613

1

phosphorylation

down-regulates activity

0.519

A potential mechanism for MK2-induced HSF1 inactivation is suggested by the findings that phosphorylation of serine 121 enhances HSF1 binding to HSP90, a major repressor of HSF1.|Phosphorylation of HSF1 by MAPK activated protein kinase 2 on serine 121, inhibits transcriptional activity and promotes HSP90 binding.

SIGNOR-279541

P63000

Q05397

0

phosphorylation

up-regulates activity

0.574

Both Src and FAK phosphorylate Rac1 at tyrosine 64.|Our investigations of direct interactions between Rac1, Src, and FAK were motivated by our previous insights into FAK augmentation of Rac1 activation during cell spreading, and the Cerione lab 's work on the interactions between Src and Cdc42 , .

SIGNOR-279652

P61244

P50539

2

binding

up-regulates activity

0.558

The role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences.

SIGNOR-240314

P48740

O75636

2

binding

up-regulates activity

0.672

H-ficolin binds to PSA, a polysaccharide produced by Aerococcus viridans. C4 was activated by H-ficolin preparations bound to PSA which had been coated on ELISA plates. These results indicate that H-ficolin is a second ficolin which is associated with MASPs and sMAP, and which activates the lectin pathway|Proteolytic activation of complement components by H-ficolin-MASP.

SIGNOR-263410

O00470

P35452

2

binding

up-regulates activity

0.422

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

SIGNOR-241232

P28482

Q05682

1

phosphorylation

down-regulates

0.539

Extracellular signal-regulated kinases (erks) phosphorylate the high molecular mass isoform of the actin-binding protein caldesmon (h-cad) at two sites (ser(759) and ser(789)) during smooth muscle stimulation. Nmr spectroscopy shows that the actin binding properties of the minimal inhibitory region of caldesmon, residues 750-779, alter upon map kinase phosphorylation of ser-759, a residue not involved in actin binding. This phosphorylation leads to markedly diminished actin affinity as a result of the loss of interaction at one of the two sites that bind to f-actin.

SIGNOR-71037

P00738

P68871

2

binding

down-regulates quantity

0.774

Haptoglobin forms a complex of extremely high affinity with Hb via a well-characterized globin site. Our results show that upon Hb-haptoglobin binding, the globin radical, loses its ability to be terminated by forming globin dimers.

SIGNOR-251815

Q9UPC5

P63096

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-256688

Q96RL1

P38398

2

binding

up-regulates

0.91

Rap80 specifically recruits brca1 to dna damage sites and functions with brca1 in g2/m checkpoint control

SIGNOR-155201

P19544

Q05066

2

binding

up-regulates

0.2

Here we report that wt1 binds to and acts synergistically with sry to activate transcription from a promoter containing sry-binding sites

SIGNOR-100345

O60858

P04234

1

polyubiquitination

down-regulates quantity by destabilization

0.2

RFP2, a gene frequently lost in various malignancies, encodes a protein with RING finger, B-box, and coiled-coil domains that belongs to the RBCC/TRIM family of proteins.Rfp2 Regulates the Stability of the ERAD Substrate CD3-δ. In summary, these experiments demonstrate that Rfp2 functions as a RING-dependent ERAD E3 ubiquitin ligase and regulates the degradation of the ER substrate, CD3-δ.

SIGNOR-271644

O43312

P08151

2

binding

up-regulates

0.543

Mim is a shh-responsive gene that can potentiate gli transcriptional activity.MIM Appears to regulate target gene expression through its association with the gli complex

SIGNOR-157650

P10242

P09488

1

transcriptional regulation

up-regulates quantity by expression

0.2

Functional analysis of the GSTM1 promoter using reporter assays indicated that both the DNA binding and transactivation domains of Myb were required for transcriptional activation

SIGNOR-253975

P33981

P27816

1

phosphorylation

down-regulates quantity by destabilization

0.2

We further uncovered that Mps1 is a kinase of MAP4, and E7-MAP4 binding blocks Mps1 phosphorylation of MAP4, thereby interrupting phosphorylation-dependent MAP4 degradation.

SIGNOR-277458

P41594

P05771

0

phosphorylation

up-regulates activity

0.354

Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.

SIGNOR-249286

P63092

P29275

2

binding

up-regulates activity

0.516

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

SIGNOR-256767

P84022

P78368

0

phosphorylation

down-regulates

0.337

Cki?2 Directly phosphorylates smad3 at ser418, leading to the increased ubiquitination and proteasomal degradation of activated smad3 following tgf-? Treatment.

SIGNOR-181069

Q9Y4D8

Q8TEK3

0

transcriptional regulation

down-regulates quantity by repression

0.2

Overexpression of DOT1L decreased the expression of HECTD4 and MYCBP2 in LNCaP, C42B, and 22rv1 cells (Supplementary Fig. 5c), suggesting that DOT1L plays a role in repressing these targets either directly or indirectly.

SIGNOR-267150

P60484

Q15831

0

phosphorylation

down-regulates activity

0.604

The C-terminal tail of PTEN is also the target of mutations in tumors. As mentioned, this region contains the main phosphorylation sites mapped to residues Ser362, Thr366, Ser370, Ser380, Thr382, Thr383, and Ser385, and the kinases involved are casein kinase 2 (CK2), GSK3_, LKB1, and MAST.84,97-101 The phosphorylation of the tail has been shown to enhance PTEN stability but at the same time decrease its phosphatase activity

SIGNOR-161118

Q00535

Q99958

1

phosphorylation

up-regulates activity

0.35

Cdk5 phosphorylates Foxc2 and activates Foxc2 dependent transcription.

SIGNOR-279156

Q9HBA0

P17252

0

phosphorylation

up-regulates activity

0.38

We conclude that the serine/threonine kinases PKC and PKA enhance activation of the TRPV4 ion channel by phosphorylation at specific sites and that phosphorylation depends on assembly of PKC and PKA by AKAP79 into a signaling complex with TRPV4.

SIGNOR-260882

P10415

Q16611

2

binding

down-regulates

0.677

Bcl-2 bind to bax or five other pro-apoptotic relatives (bak, bad, bik, bid or bim)

SIGNOR-55546

Q5MNZ9

Q676U5

2

binding

up-regulates quantity

0.606

WIPI1 assists WIPI2 in recruiting ATG16L for LC3 lipidation. WIPI1-WIPI2 heterodimer may function more efficiently in ATG16L complex recruitment.

SIGNOR-268477

P46937

P31947

0

relocalization

down-regulates activity

0.461

Verteporfin increases the level of 14-3-3σ, which promotes the translocation of YAP from nucleus to cytoplasm.

SIGNOR-278130

P35247

P17676

0

transcriptional regulation

up-regulates quantity by expression

0.251

Cotransfection of C/EBPalpha, C/EBPbeta, or C/EBPdelta cDNA in H441 lung adenocarcinoma cells significantly increased the luciferase activity of a wild-type SP-D promoter construct containing 698 bp of upstream sequence (SS698). Transfection of C/EBP also increased the level of endogenous SP-D mRNA in H441 cells| Thus, interactions among C/EBP elements in the near-distal promoter can modulate the promoter activity of SP-D.

SIGNOR-254045

Q96GD4

P68431

1

phosphorylation

down-regulates activity

0.2

Histone code pathway involving h3 s28 phosphorylation and k27 acetylation activates transcription and antagonizes polycomb silencingaurora-b phosphorylates histone h3 at serine28 with regard to the mitotic chromosome condensation

SIGNOR-171717

P04637

Q05655

0

phosphorylation

up-regulates

0.677

Here, we show that the pro-apoptotic kinase, protein kinase c delta (pkcdelta), is involved in phosphorylation of p53 on ser(46). pkcdelta potentiates p53-dependent apoptosis by ser(46) phosphorylation in response to genotoxic stress.

SIGNOR-143382

P04637

P12931

0

phosphorylation

down-regulates quantity by destabilization

0.524

We recently found that ISGylation of the p53 tumor suppressor is an important novel mechanism to control its stability. Here we identified that Isg15-dependent regulation of p53 can be enhanced by different oncogenes. We further show that the Src-mediated phosphorylation of p53 on Tyr126 and Tyr220 has a positive effect on p53 ISGylation by enhancing Herc5 binding.

SIGNOR-276668

P27361

O75030

1

phosphorylation

down-regulates quantity by destabilization

0.542

More interestingly, ERK-dependent phosphorylation of MITF at Ser 73 is essential for MITF ubiquitinilation and degradation (87). Putting together all these findings, it can be proposed that MAPK activation inhibits melanogenesis due to an increased MITF degradation which is dependent on the MAPK-induced MITF phosphorylation and ubiquitinilation. In summary, although the phosphorylation of MITF at Ser73 increases its intrinsic transcriptional activity, this phosphorylation also targets MITF to the proteasome for its degradation. Consequently, the decrease in MITF levels leads to a down-regulation of melanogenic enzymes expression and to an inhibition of melanogenesis.

SIGNOR-249620

Q9BXM7

O43318

1

phosphorylation

up-regulates activity

0.33

PINK1 also enhances the association between TRAF6 and TAK1, phosphorylates TAK1, and stimulates polyubiquitination of TAK1.

SIGNOR-279644

Q8IXQ5

Q9H6E5

2

binding

down-regulates quantity by destabilization

0.2

Kelch-like protein 7 (KLHL7) is a component of Cul3-based Cullin-RING ubiquitin ligase. In this study, we report that KLHL7 increases terminal uridylyl transferase 1 (TUT1) ubiquitination involved in nucleolar integrity.

SIGNOR-272318

Q14934

P51812

0

phosphorylation

up-regulates

0.385

The results indicated that rsk2 phosphorylated two additional sites at ser289 (peptide 2) and ser344 (peptide 3)rsk2 induced nuclear localization of nfat3. Rsk2 phosphorylated nfat3 in vitro (km=3.559 microm), and activation of nfat3 by rsk2 enhanced the promoter activity of nfat3 downstream target genes in vivo.

SIGNOR-234473

Q08209

Q9NZJ5

0

phosphorylation

down-regulates activity

0.2

CN becomes phosphorylated by PERK, decreasing its activity.|Finally, evidence is presented that PERK phosphorylates CN-A at low resting levels of Ca 2+.

SIGNOR-278933

Q13309

P10244

1

polyubiquitination

down-regulates quantity by destabilization

0.378

P19Skp1 and Cul-1 bind to the F-box protein p45Skp2 to form a complex (SCF) that functions as E3 ubiquitin ligase.We show that B-Myb physically and functionally interacts with components of the Cdc34-SCFp45Skp2 ubiquitin pathway and propose that B-Myb degradation may be required for controlling the correct alternation of events during progression through the cell division cycle.

SIGNOR-272572

P25025

P14174

2

binding

up-regulates activity

0.382

We identify the chemokine receptors CXCR2 and CXCR4 as functional receptors for MIF [] By activating both CXCR2 and CXCR4, MIF displays chemokine-like functions and acts as a major regulator of inflammatory cell recruitment and atherogenesis.

SIGNOR-252061

P17252

P43629

1

phosphorylation

down-regulates activity

0.2

Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of Ser(394) by protein kinase C slightly suppresses KIR3DL1 inhibitory function, and reduces receptor internalization and turnover.Both CKII and PKC phosphorylate KIR3DL1 in vitro. Ser364 can be phosphorylated after phosphorylation of Ser367 by CKII.

SIGNOR-276080

P10828

P23769

2

binding

down-regulates activity

0.2

We found that the T3-bound TR inhibits this reporter construct driven by GATA2 alone, indicating that the target of T3-bound TR repression is GATA2.

SIGNOR-267256

O15344

Q13153

0

phosphorylation

up-regulates activity

0.2

Pak1 phosphorylates the N-terminus of Mid1 to promote its association with cortical nodes.|Pak1 promotes Mid1 localization to cortical nodes.

SIGNOR-279307

Q13555

Q15746

1

phosphorylation

down-regulates activity

0.331

Phosphorylation of MLC kinase by CaM protein kinase II increased the dissociation constant of MLC kinase for calmodulin about 10 times without changing the Vmax. The location of the phosphorylation sites was identified by isolating and sequencing the tryptic phosphopeptides of MLC kinase. The preferred site was identified as serine 512 and the second site as serine 525. These sites are the same as the sites phosphorylated by cAMP-dependent protein kinase.

SIGNOR-250700

Q9H2X6

Q9UK99

2

binding

down-regulates quantity by destabilization

0.404

O clarify the role of PML in transcription regulation, we purified the PML complex and identified Fbxo3 (Fbx3), Skp1, and Cullin1 as novel components of this complex. Fbx3 formed SCF(Fbx3) ubiquitin ligase and promoted the degradation of HIPK2 and p300 by the ubiquitin-proteasome pathway.

SIGNOR-271741

P06493

P38398

1

phosphorylation

up-regulates

0.497

However, shrna-mediated depletion of cdk1 alone or small molecule cdk1 inhibition abrogated s phase cell-cycle arrest and the phosphorylation of a subset of atr/atm targets after dna damage. Loss of dna damage-induced checkpoint control was caused by a reduction in formation of brca1-containing foci. Mutation of brca1 at s1497 and s1189/s1191 resulted in loss of cdk1-mediated phosphorylation and also compromised formation of brca1-containing foci.

SIGNOR-72087

Q16584

P45985

1

phosphorylation

up-regulates

0.625

These data suggest that mlk-3 phosphorylates sek1 directly and that it does so specifically on those residues known to activate sek1 in vivo.

SIGNOR-75836

O14559

P06241

0

phosphorylation

down-regulates

0.461

Tcgap interacted with fyn and was phosphorylated by fyn, with tyr-406 in the gap domain as a major fyn-mediated phosphorylation site. Fyn suppressed the gap activity of wild-type tcgap

SIGNOR-147156

P50406

Q00535

0

phosphorylation

down-regulates activity

0.374

Cdk5 phosphorylates the 5-HT6R on serine 350 (Ser350)|This suggests that the 5-HT6R is unable to interact with GPRIN1 when it is phosphorylated by Cdk5.

SIGNOR-264407

P35222

Q9NQU5

0

phosphorylation

down-regulates quantity

0.2

Moreover, we find that \u03b2-catenin is also localized with PAK6 in cell-cell junctions and is a novel PAK6 substrate.|PAK6 binds to and phosphorylates beta-catenin.

SIGNOR-279546

Q16206

Q05655

0

phosphorylation

up-regulates

0.2

Tnox is phosphorylated by protein kinase c_ (pkc_) both in vitro and in vivo. Replacement of serine-504 with alanine significantly reduces phosphorylation by pkc_. C. overexpression of the s504a tnox mutant leads to diminished cell proliferation and migration, reflecting reduced stability of the unphosphorylatable tnox mutant protein.

SIGNOR-197706

Q9GZV5

Q99594

2

binding

up-regulates

0.699

When dephosphorylated, yap/taz enter nuclei and induce gene transcription by interacting with transcription factors tead14.

SIGNOR-201415

Q14344

P50406

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-257443

P40189

O14543

2

binding

down-regulates activity

0.652

SOCS3 binds specific receptor-JAK complexes to control cytokine signaling by direct kinase inhibition. The inhibitory protein SOCS3 plays a key part in the immune and hematopoietic systems by regulating signaling induced by specific cytokines. SOCS3 functions by inhibiting the catalytic activity of Janus kinases (JAKs) that initiate signaling within the cell.

SIGNOR-255328

O60462

Q99985

2

binding

up-regulates

0.585

Our experiments establish that small peptides containing the consensus decd sequence of sperm fertilinbeta bind specifically to an alpha6beta1 integrin receptor on the egg membrane. We conclude that fertilinbeta binds directly to the alpha6beta1 integrin on the egg surface and this partnership mediates sperm-egg fusion.

SIGNOR-147564

Q92997

P31431

2

binding

up-regulates

0.247

Like other wnt co-receptors, syndecan 4 directly interacts with dvl during pcp 1.

SIGNOR-199638

P16885

P43405

0

phosphorylation

up-regulates activity

0.753

Syk in turn phosphorylates and activates the B cell linker protein (BLNK), phosphoinositide 3-kinase (PI3K) and phospholipase C\u03b32 (PLC\u03b32).|Syk in turn phosphorylates and activates the B cell linker protein (BLNK), phosphoinositide 3-kinase (PI3K) and phospholipase Cgamma2 (PLCgamma2).

SIGNOR-278995

P28482

P49841

1

phosphorylation

down-regulates activity

0.383

We demonstrate that insulin-mediated activation of ERK1/2 results in phosphorylation of GSK3β at S9 independently of Akt/mTORC1 activity in Tsc2 null mouse embryonic fibroblasts. In addition, we show that inhibition of ERK1/2 rescues GSK3β activity and restores protein synthesis in Tsc2 −/− MEFs to normal levels

SIGNOR-262524

P35968

Q12913

0

dephosphorylation

down-regulates

0.699

The autoactivation residues y1054 and y1059 are targeted by dep-1 and this results in the inhibition of kinase activity and the consequent general dephosphorylation of vegfr2.

SIGNOR-181672

O15530

P05129

1

phosphorylation

up-regulates

0.2

One of the most studiedevents controlled by ptdins(3,4,5)p3, comprises the activation of aof agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum- and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated.

SIGNOR-126072

Q9Y5X1

P50570

2

binding

up-regulates

0.812

Snx9 binds directly to bothdynamin-1 anddynamin-2. Moreover by stimulatingdynaminassembly, snx9 stimulatesdynamin's basal gtpase activity and potentiates assembly-stimulated gtpase activity on liposomes.

SIGNOR-133976

P63092

O15169

2

binding

up-regulates

0.381

We show that pge2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (g protein) coupled receptor, ep2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase akt by free g protein bg subunits and the direct association of the g protein as subunit with the regulator of g protein signaling (rgs) domain of axin.

SIGNOR-141789

Q12772

P04035

1

transcriptional regulation

up-regulates quantity by expression

0.492

The processed SREBP2, designated nuclear SREBP2 (nSREBP2), then enters the nucleus as a homodimer, binds to the sterol regulatory element (SRE) sequence in the promoters of target genes, including HMGCR and SQLE (encoding squalene monooxygenase), and upregulates their transcription

SIGNOR-265161

P28482

Q9UPP1

1

phosphorylation

down-regulates activity

0.2

Upon IFNgamma treatment, PHF8 is phosphorylated by ERK2 and evicted from the promoters, which correlates with an increase in H4K20me1 and H3K4me3 levels.

SIGNOR-279745

Q7Z6Z7

P20226

1

ubiquitination

down-regulates quantity

0.337

Having established that Huwe1 mediates TBP ubiquitination in vitro, we then asked which E2 conjugating enzymes work best with Huwe1 in this reaction.|Upregulation of Huwe1 expression during myogenesis induces TBP degradation and myotube differentiation.

SIGNOR-278696

Q16236

P04179

1

transcriptional regulation

up-regulates quantity by expression

0.45

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

SIGNOR-254652

Q99990

P51812

0

phosphorylation

down-regulates activity

0.2

Site-directed mutagenesis and immunoprecipitation experiments revealed that RSK2 phosphorylated VGLL1 at S84 in the presence of TGF-β. Mutation of VGLL1 at S84 suppressed VGLL1-TEAD4 binding and the subsequent transcriptional activation of matrix metalloprotease 9 (MMP9).

SIGNOR-273842

P19525

P40763

1

phosphorylation

up-regulates activity

0.612

Silencing PKR gene expression in HepG2 cells with siRNA reduced STAT3 phosphorylation at Tyr705 and Ser727 (XREF_FIG).|The results also revealed that PKR activates STAT3, a transcription factor associated with primary liver tumors, which is suggested to promote tumor cell proliferation.

SIGNOR-279613

P06493

Q9BW19

1

phosphorylation

up-regulates quantity by stabilization

0.458

We confirmed that CDK1 phosphorylates Ser6 (Supplementary Fig S5B) and demonstrated that KIFC1 displays CDK1-mediated resistance to ubiquitination by the APC/C (Fig S5C).

SIGNOR-277294

P38398

Q13363

0

transcriptional regulation

down-regulates quantity by repression

0.603

Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor with oncogenic potential. We found CtBP1 was recruited to the promoter regions of Brca1 and E-cadherin genes in breast cancer cells.

SIGNOR-259196

Q8NEV9

Q6UWB1

2

binding

up-regulates

0.711

Wsx-1 and glycoprotein 130 constitute a signal-transducing receptor for il-27.

SIGNOR-121799

Q9Y448

Q8N4N8

1

relocalization

down-regulates activity

0.407

The protein astrin has been shown to remove Kif2b from kinetochores in metaphase through competitive binding of CLASP1 (Manning et al., 2010 blue right-pointing triangle). During prometaphase, Aurora B kinase activity prevents astrin from localizing to kinetochores (Manning et al., 2010 blue right-pointing triangle; Schmidt et al., 2010 blue right-pointing triangle). This permits Kif2b to localize to kinetochores to destabilize k-MT attachments to execute error correction through Plk1-dependent recruitment and activation.

SIGNOR-252053

O43852

P38435

2

binding

down-regulates activity

0.401

Results are presented that demonstrate that the endoplasmic reticulum chaperone protein calumenin is associated with gamma-carboxylase and inhibits its activity.

SIGNOR-265910

Q13618

Q9Y4X5

2

binding

up-regulates activity

0.314

Here, we provide evidence that Ariadne RBR E3 ubiquitin ligases such as TRIAD1 and HHARI can bind and be activated by CRL complexes. Whereas TRIAD1 specifically associates with CUL5–RBX2, HHARI is more promiscuous towards cullin types and associates with RBX1-associated cullins 1, 2, 3, and 4A. Interestingly, both TRIAD1 and HHARI show a strong preference for binding the neddylated form of the cullin. Our data suggest a novel function of NEDD8 in directing specific CRLs to Ariadne RBR ligases, which in turn exert influence on the levels of their cognate neddylated cullin.

SIGNOR-268846

P07339

P05067

1

cleavage

down-regulates quantity by destabilization

0.489

The precise cathepsin D cleavage sites within these recombinant betaAPP substrates were identified using this technique. Both recombinant substrates were cleaved at the following sites: Leu49-Val50, Asp68-Ala69, Phe93-Phe94. | two additional cleavage sites near the amino terminus of betaA4, Glu-3-Val-2 and Glu3-Phe4, were observed, indicating that cathepsin D cleavage of betaAPP is influenced by the structural integrity of the substrate. Taken together, these results indicate that in vitro, cathepsin D is unlikely to function as gamma-secretase; however, the ability of this enzyme to efficiently cleave betaAPP substrates at nonamyloidogenic sites within the molecule may reflect a role in betaAPP catabolism.

SIGNOR-261767

P19174

Q9UJZ1

2

binding

up-regulates activity

0.2

In these studies, we also found that SLP-2 interacted with Lck, ZAP70, LAT, and PLC-gamma1 during the 30-min period following stimulation in vitro|The SLP-2-associated pool of these molecules became phosphorylated/activated in a sequential manner, a profile compatible with their temporal involvement in early TCR signalling.

SIGNOR-260378

O14746

P12931

0

phosphorylation

down-regulates

0.418

Hydrogen peroxide triggers nuclear export of telomerase reverse transcriptase via src kinase family-dependent phosphorylation of tyrosine 707

SIGNOR-102097

Q16659

P06493

0

phosphorylation

up-regulates

0.484

Using ms analysis, we identified four novel phosphorylation sites, ser684, ser688, thr698 and ser705, located at the extreme c-terminus of erk3. All four sites are followed by a proline residue. We have shown that purified cyclin b-cdk1 (cyclindependent kinase 1) phosphorylates these sitesalanine substitution of the four c-terminal phosphorylation sites markedly decreased the half-life of erk3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase.

SIGNOR-164499

O76074

O94844

2

binding

down-regulates quantity by destabilization

0.2

RhoBTB1 augmented the cGMP response to nitric oxide by restraining the activity of phosphodiesterase 5 (PDE5) by acting as a substrate adaptor delivering PDE5 to the Cullin-3 E3 Ring ubiquitin ligase complex for ubiquitination inhibiting PDE5.

SIGNOR-272312

Q9UPN4

P49137

0

phosphorylation

down-regulates quantity

0.291

We identify CEP131 as a major Centriolar satellites-associated substrate of p38-dependent, MK2-mediated phosphorylation on two defined residues and show that these modifications promote binding to 14-3-3 proteins, in turn leading to cytoplasmic sequestration of CEP131 and associated Centriolar satellites factors.|We therefore conclude that MK2 dependent phosphorylation of CEP131 at S47 and S78 and the ensuing binding of 14-3-3 proteins play an essential role in triggering stress induced remodelling of CS.

SIGNOR-278181

Q9Y6D9

P12270

2

binding

up-regulates

0.486

Tpr directly binds to mad1 and mad2. / depletion of tpr decreases the levels of mad1 at kinetochores during prometaphase, correlating with the inability of mad1 to activate mad2, which is required for inhibiting apc(cdc20).

SIGNOR-181918

P46020

Q16816

2

binding

down-regulates activity

0.691

Phk is among the most complex of the protein kinases so far elucidated. It has one catalytic (gamma) subunit and three different regulatory (alpha, beta, and delta) subunits, a molecular mass of 1.3 X 106 daltons, and each holoenzyme molecule is presumed to contain four molecules of each subunit. The three regulatory subunits inhibit the phosphotransferase activity of the gamma subunit.

SIGNOR-267405

Q99250

P68400

0

phosphorylation

up-regulates activity

0.2

We found that the ankyrin-binding motif of Na(v)1.2 that determines channel concentration at the AIS depends on a glutamate residue (E1111), but also on several serine residues (S1112, S1124, and S1126). We showed that phosphorylation of these residues by protein kinase CK2 (CK2) regulates Na(v) channel interaction with ankyrins. | inhibition of CK2 activity reduced sodium channel accumulation at the AIS of neurons. In conclusion, CK2 contributes to sodium channel organization by regulating their interaction with ankyrin G.

SIGNOR-275761

P46527

P12931

0

phosphorylation

down-regulates

0.496

Src regulates p27 stability through phosphorylation of p27 at tyrosine 74 and tyrosine 88. Our data indicate that phosphorylation by src impairs the cdk2 inhibitory action of p27

SIGNOR-152839

Q13158

P25445

2

binding

up-regulates activity

0.91

Aggregation-induced conformational changes in fas lead to the formation of the death-inducing signalling complex (disc) which involves recruitment of the adaptor protein fadd/mort1 through a homotypic interaction of death domains, present in both the intracellular region of fas and the c-terminus of fadd.

SIGNOR-176651

P49116

P22888

1

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

P31749

Q13882

0

phosphorylation

up-regulates

0.476

Here we demonstrate that AKT is a direct substrate of PTK6 and that AKT tyrosine residues 315 and 326 are phosphorylated by PTK6.

SIGNOR-252622

Q05513

Q8N2W9

1

phosphorylation

down-regulates quantity by destabilization

0.519

In this study, we discovered a new protein isoform encoded by KIAA0317, termed fibrosis-inducing E3 ligase 1 (FIEL1), which potently stimulates the TGFbeta signaling pathway through the site-specific ubiquitination of PIAS4.FIEL1 targets PIAS4 using a double locking mechanism that is facilitated by the kinases PKCzeta and GSK3beta. Specifically, PKCzeta phosphorylation of PIAS4 and GSK3beta phosphorylation of FIEL1 are both essential for the degradation of PIAS4.|These experiments suggested that PKCzeta is an authentic regulator of PIAS4 protein stability; Q21 and phosphorylated S18 of PIAS4 are both required for FIEL1 interaction.

SIGNOR-275513

Q9UMX1

P08151

2

binding

down-regulates activity

0.949

Here we characterize structural and functional determinants of Su(fu) required for Gli regulation and show that Su(fu) contains at least two distinct domains: a highly conserved carboxy-terminal region required for binding to the amino-terminal ends of the Gli proteins and a unique amino-terminal domain that binds the carboxy-terminal tail of Gli1. While each domain is capable of binding to different Gli1 regions independently, interactions between Su(fu) and Gli1 at both sites are required for cytoplasmic tethering and repression of Gli1

SIGNOR-249591

Q9P2R6

Q07812

1

relocalization

up-regulates activity

0.2

We detected RERE protein mainly in the nucleus, where it colocalizes with the promyelocytic leukemia protein in promyelocytic leukemia oncogenic domains (PODs). Overexpression of RERE recruits a fraction of the proapoptotic protein BAX to PODS: This observation correlates with RERE-induced apoptosis, which occurs in a caspase-dependent manner.

SIGNOR-264485

Q00535

P16220

1

phosphorylation

up-regulates activity

0.374

CDK5 Activates the Self-Renewal Regulator CREB1 in GSCs.|Our data indicate that CDK5, which has previously been shown to activate CREB1 through cAMP and PKA in dopamine neurons present in the ventral tegmental area, can directly bind with and phosphorylate CREB1 in a PKA and cAMP independent manner, at least in GSCs.

SIGNOR-279682

P35658

Q13485

2

binding

up-regulates

0.561

We demonstrate that smad3 and smad4 are capable of interaction with the nucleoporin can/nup214, and this interaction is required for nuclear import

SIGNOR-117647

P10082

P50391

2

binding

up-regulates

0.669

Human y4 bound human pp family members in i-pyy membrane binding assays with a distinctive rank order (table 1): pp > pyy > npy > npy free acid.

SIGNOR-29767

Q14524

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-253418

Q06187

P05771

0

phosphorylation

down-regulates activity

0.382

We provide direct evidence that PKCbeta acts as a feedback loop inhibitor of Btk activation. Inhibition of PKCbeta results in a dramatic increase in B-cell receptor (BCR)-mediated Ca2+ signaling. We identified a highly conserved PKCbeta serine phosphorylation site in a short linker within the Tec homology domain of Btk. Mutation of this phosphorylation site led to enhanced tyrosine phosphorylation and membrane association of Btk, and augmented BCR and FcepsilonRI-mediated signaling in B and mast cells, respectively. | This deductive analysis indicated that PKCbeta phosphorylates S180 in the region bisecting the Btk motif (BM) and the PRR of the TH domain.

SIGNOR-249110

Q96T60

P78527

0

phosphorylation

up-regulates

0.649

We demonstrate that pnkp is phosphorylated by the dna-dependent protein kinase (dna-pk) and ataxia-telangiectasia mutated (atm) in vitro. The major phosphorylation site for both kinases was serine 114, with serine 126 being a minor site. Purified pnkp protein with mutation of serines 114 and 126 had decreased dna kinase and dna phosphatase activities and reduced affinity for dna in vitro.

SIGNOR-176020

Q7Z6J0

Q02779

2

binding

up-regulates

0.355

Taken together, these findings support a model in which apoptotic stimuli or posh overexpression induce direct association between posh and inactive mlks.

SIGNOR-97003

Q6ZMT4

Q16665

0

transcriptional regulation

up-regulates quantity by expression

0.2

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

SIGNOR-271572

P11802

P19532

1

phosphorylation

up-regulates activity

0.2

CDK4 and CDK6 interact with TFEB and TFE3 in the nucleus We next investigated how CDK4 and CDK6 activate TFEB and TFE3 .|We found that CDK4 and CDK6 interact with and phosphorylate nuclear TFEB and TFE3, thereby promoting their shuttling to the cytoplasm.

SIGNOR-279514

P27540

Q16665

2

binding

up-regulates activity

0.787

The functional transcription factor exists as a heterodimeric complex consisting of HIF-1alpha and the aryl hydrocarbon receptor nuclear translocator (ARNT). Association of HIF-1 with ARNT is required for its activity; however, no other role has been ascribed to this interaction.

SIGNOR-253720

P28482

Q96EP5

1

phosphorylation

down-regulates activity

0.2

Further experiments showed that DAZAP1 was phosphorylated stoichiometrically in vitro by ERK2 (extracellular-signal-regulated protein kinase 2) at two Thr-Pro sequences (Thr269 and Thr315), and that both sites became phosphorylated in HEK-293 (human embryonic kidney 293) cells in response to PMA or EGF (epidermal growth factor), or RAW 264.7 macrophages in response to LPS. Phosphorylation of the ARE-binding protein DAZAP1 by ERK2 induces its dissociation from DAZ

SIGNOR-262970