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
P05106	P49758	2	binding	down-regulates	0.2	Numb binds to integrin-betas and localizes to clathrin-coated structures	SIGNOR-156762
P48730	P51532	1	phosphorylation	down-regulates quantity by destabilization	0.2	We reveal that CK1δ phosphorylates Brg1 at Ser31/Ser35 residues to facilitate the binding of Brg1 to FBW7, leading to ubiquitination-mediated degradation.	SIGNOR-277407
P54646	Q96RR4	0	phosphorylation	up-regulates	0.619	These data indicate that the camkks function in intact cells as ampkks, predicting wider roles for these kinases in regulating ampk activity in vivo.	SIGNOR-138364
P45983	O95140	1	phosphorylation	down-regulates quantity	0.428	We demonstrate that a critical component of the mitochondrial fusion apparatus, the mitofusin Mfn2, is a target for phosphorylation in response to a variety of cellular stresses. We provide direct evidence that JNK mediates this phosphorylation.	SIGNOR-274138
Q13315	Q13535	0	phosphorylation	up-regulates activity	0.747	Atr-dependent phosphorylation and activation of atm in response to uv treatment or replication fork stalling. Here, we show that atm phosphorylation at ser1981, a characterised autophosphorylation site, is atr-dependent and atm-independent following replication fork stalling or uv treatment	SIGNOR-150870
Q9UKP6	P50148	2	binding	up-regulates activity	0.435	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-257377
P63000	O94988	0	gtpase-activating protein	down-regulates activity	0.435	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260502
O95644	Q14164	0	phosphorylation	up-regulates activity	0.2	Phosphorylation of NFATC1 at PIM1 target sites is essential for its ability to promote prostate cancer cell migration and invasion. Here we have identified ten PIM1 target sites in NFATC1 and found that prevention of their phosphorylation significantly decreases the transcriptional activity as well as the pro-migratory and pro-invasive effects of NFATC1 in prostate cancer cells.	SIGNOR-276778
P42568	O00141	0	phosphorylation	down-regulates activity	0.509	In addition to Nedd4-2, Sgk1 also phosphorylates Af9, forkhead like transcription factor FOXO3a and several other substrates.\|Sgk1 impairs the ability of Af9 to interact with Dot1a at these subregions without impacting Af9 DNA binding activity, leading to targeted histone H3 K79 hypomethylation.	SIGNOR-279111
Q9BY66	P68431	1	demethylation	up-regulates activity	0.2	KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.	SIGNOR-264308
O75914	P04049	1	phosphorylation	up-regulates	0.556	The protein kinase pak3 positively regulates raf-1 activity through phosphorylation of serine 338.	SIGNOR-62043
Q9NRD1	O14757	2	binding	down-regulates quantity by destabilization	0.496	Here, we report that DNA damage not only activates Chk1, but also exposes a degron-like region at the carboxyl terminus of Chk1 to an Fbx6-containing SCF (Skp1-Cul1-F box) E3 ligase, which mediates the ubiquitination and degradation of Chk1 and, in turn, terminates the checkpoint.	SIGNOR-271879
Q14938	P23352	1	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268884
P25101	P08754	2	binding	up-regulates activity	0.434	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-257165
Q93097	O75197	2	binding	up-regulates	0.588	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors andinitiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-131780
O14965	Q9UNN5	1	phosphorylation	down-regulates activity	0.2	This study reports that aurora-a (aur-a) phosphorylates fas-associated factor-1 (faf1) at ser-289 and ser-29 our findings support the negative feedback regulation of aur-a via phosphorylation of the death-promoting protein, faf1	SIGNOR-180891
O15182	O43303	2	binding	up-regulates activity	0.418	We report that CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo. our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis.	SIGNOR-265968
O96018	P61764	2	binding	up-regulates activity	0.501	Munc18-1 is a neuronal protein that interacts with syntaxin 1 and is required for synaptic vesicle exocytosis. We have now identified two Munc18-1-interacting proteins called Mint1 and Mint2 that may mediate the function of Munc18-1.	SIGNOR-264036
Q9BWP8	P48740	2	binding	up-regulates activity	0.622	On the basis of the significant concentration of CL-11 in circulation and CL-11's interaction with various microorganisms and MASP-1 and/or MASP-3, it is conceivable that CL-11 plays a role in activation of the complement system and in the defense against invading microorganisms.	SIGNOR-263409
P60520	Q13501	2	binding	up-regulates activity	0.862	P62 binds both to lc3a and -b and the related gabarap family proteins/this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguisha	SIGNOR-156307
Q99541	P35790	0	phosphorylation	down-regulates quantity by destabilization	0.2	In addition, as a protein kinase, CHKalpha2 phosphorylates PLIN2 at Tyrosine 232 and PLIN3 at Tyrosine 251. Phosphorylated PLIN2 and PLIN3 are separated from lipid droplets and degraded by Hsc70-mediated autophagy, thereby promoting lipid droplet lipolysis, fatty acid oxidation and glioblastoma growth	SIGNOR-267649
P41145	P01213	2	binding	up-regulates activity	0.668	We recently cloned a human kappa opioid receptor and stably expressed it in Chinese hamster ovary (CHO) cells. In this study, the effects of activation of the human kappa receptor by agonists on [35S]GTPgammaS binding to CHO cell membranes were examined.. The rank order of potencies of opioid ligands tested in stimulating [35S]GTPgammaS binding was dynorphin A 1-17 > (+/-)-ethylketocyclazocine > beta-funaltrexamine, (-)-U50,488H, tifluadom > nalorphine > pentazocine, nalbuphine > buprenorphine.	SIGNOR-258411
P08172	P63096	2	binding	up-regulates activity	0.511	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-256685
O75385	Q9Y2H1	0	phosphorylation	down-regulates quantity	0.2	STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination	SIGNOR-270348
P00519	Q13148	1	phosphorylation	up-regulates quantity	0.2	The phosphorylation of tyrosine 43 of TDP-43 by c-Abl led to increased TDP-43 levels in the cytoplasm and increased the formation of G3BP1-positive stress granules in SH-SY5Y cells.	SIGNOR-279135
Q8NFH5	P53350	0	phosphorylation	down-regulates activity	0.415	Collectively, these data show that mitotic hyperphosphorylation of Nup53 by CDK1 and PLK1 contributes to its removal from NPCs.\|The combined mutation of the CDK1 and PLK1 sites to phosphomimetic residues almost completely abolished NPC integration of Nup53, indicating that hyperphosphorylation of Nup53 might be incompatible with its NPC association.	SIGNOR-279252
Q9NZI6	P06493	0	phosphorylation	up-regulates activity	0.2	In addition, overexpression of TFCP2L1 and CDK1 in T24 cells increased clonogenic activity in a clonogenic limiting dilution assay (Fig\u00a05H), confirming the importance of CDK1\u2010TFCP2L1 pathways for the stemness features of BC cells.High levels of co\u2010expression of p\u2010TFCP2L1 and CDK1 were associated with distant metastasis in our cohort of BC patients (Table\u00a01).\|Tfcp2l1 Thr177 phosphorylation by CDK1 is essential for proliferation and cell cycle progression of ESCs.\|Tfcp2l1 is phosphorylated at Thr177 by CDK1.	SIGNOR-278472
Q8N2Q7	Q9P2S2	2	binding	up-regulates activity	0.829	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264154
Q92793	Q00978	1	acetylation	up-regulates activity	0.361	CBP was also the most effective one among the acetyltransferases tested for catalyzing IRF9 acetylation in 293T cells. [²] Figure 5 (F) K81 acetylation is required for IRF9 dimerization between the N-terminal 1-118 and the C-terminal 340-393 regions. In the left panel, Myc-DBD (1- 118) of IRF9 was cotransfected with 118-393, 118-339, or 1-393 (FL) of IRF9 in 293T cells. Anti-IRF9 (C-terminal region) precipitates were analyzed with anti-Myc or anti-IRF9. Anti-IRF9 precipitates, prepared from 293T cells cotransfected with the C-terminal fragment 118-393 of IRF9 and Myctagged DBD of different forms, were analyzed with anti-Myc or anti-IRF9 (right panel).	SIGNOR-217787
Q04206	Q9Y618	1	relocalization	down-regulates activity	0.404	Furthermore, overexpression of Flt3-ITD led to a partial relocalization of SMRT protein from the nucleus to the cytoplasm. This indicates that shuttling of p65 was necessary for Flt3-ITD-mediated SMRT nuclear export.	SIGNOR-261539
Q5TCY1	P10636	1	phosphorylation	down-regulates	0.451	Direct tau phosphorylation by ttbk1 at ser198, ser199, ser202 and ser422, which are also phosphorylated in phfs. Ttbk1 also induces tau aggregation in human neuronal cells in a dose-dependent manner. We conclude that ttbk1 is a neuron-specific dual kinase involved in tau phosphorylation at ad-related sites and is also associated with tau aggregation.	SIGNOR-148970
O00744	Q14332	2	binding	up-regulates	0.64	Inhibition of adipogenesis by wnt10b is likely mediated by wnt receptors, frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor-related proteins 5 and 7	SIGNOR-89137
Q96M98	O60260	0	polyubiquitination	down-regulates quantity by destabilization	0.2	In this study, we found that CHIP promotes Parkin-mediated Pael-R ubiquitination and subsequent degradation. In vitro ubiquitination assays suggested that only a combination of both Parkin and its cofactor CHIP function as a ubiquitin ligase, which is able to sufficiently ubiquitinate Pael-R in vivo (Figure 6).	SIGNOR-272889
Q14432	P17252	0	phosphorylation	up-regulates	0.2	Protein kinase c-mediated phosphorylation and activation of pde3a regulate camp levels in human platelets. together, these results demonstrate that platelet activation stimulates pkc-dependent phosphorylation of pde3a on ser(312), ser(428), ser(438), ser(465), and ser(492) leading to a subsequent increase in camp hydrolysis and 14-3-3 binding.	SIGNOR-184452
Q15759	P10636	1	phosphorylation	down-regulates activity	0.341	Phosphorylation of tau by SAPK3 and SAPK4 resulted in a marked reduction in its ability to promote microtubule assembly.\|Tau phosphorylated by SAPK2b and SAPK2a also reacted with AT8, whereas AT8 failed to recognise tau phosphorylated by SAPK1gamma.	SIGNOR-279637
P49810	Q96BI3	2	binding	up-regulates	0.923	Gamma secretase subunit. Leads to ps1/ps2 eterodimer complex stabilisation. By using co-immunoprecipitation and nickel affinity pull-down approaches, we now show that mammalian aph-1 (maph-1), a conserved multipass membrane protein, physically associates with nicastrin and the heterodimers of the presenilin amino- and carboxyl-terminal fragments in human cell lines and in rat brain.	SIGNOR-93265
O94768	Q15139	0	phosphorylation	up-regulates activity	0.252	Coexpression of DRAK2 and a constitutively active PKD mutant (CA-PKD1; PKD1-S738/742E) were sufficient to greatly enhance DRAK2 autophosphorylation, supporting the hypothesis that PKD catalytic activity promotes DRAK2 function.\|We note that PKD was able to phosphorylate DRAK2 outside of its C terminus, suggesting that PKD mediated phosphorylation occurs on a site in the 1-290 fragment of DRAK2.	SIGNOR-279753
Q9UGL1	O00257	2	binding	up-regulates activity	0.399	Our results clearly showed that the PcG protein hPc2 interacted with the N-terminus of JARID1B both in vivo and in vitro. It is interesting that the C-terminus of hPc2 was essential for the interaction and transcriptional co-repression.	SIGNOR-226447
Q05655	Q01995	1	phosphorylation	down-regulates activity	0.327	Of the three consensus protein kinase C or casein kinase II phosphorylation sites in SM22, only Ser-181 was readily phosphorylated by protein kinase C in vitro, and such phosphorylation greatly decreased actin binding.	SIGNOR-249061
P53041	Q969Q6	2	binding	up-regulates activity	0.346	Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and function	SIGNOR-272480
Q8WZ64	P61586	1	gtpase-activating protein	down-regulates activity	0.514	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260453
P29597	Q13118	1	phosphorylation	down-regulates activity	0.438	These data strongly supported that Tyk2 phosphorylates TIEG1.\|Tyrosine kinase Tyk2-mediated phosphorylation of TIEG1 at Tyr179 promoted noncanonical K-27-linked polyubiquitination, which inhibited TIEG1 nuclear translocation.	SIGNOR-279575
Q6ZNA4	O15105	1	ubiquitination	down-regulates	0.736	Axin is a scaffold protein in tgf-beta signaling that promotes degradation of smad7 by arkadia	SIGNOR-119666
Q13263	Q9UBF1	2	binding	up-regulates activity	0.505	In this study, we demonstrated that the tripartite motif-containing protein 28 (TRIM28) binds directly to and promotes FBP1 for ubiquitination and degradation. MAGE-A3 and MAGE-C2, which are known to be overexpressed in HCC, can enhance TRIM28-dependent degradation of FBP1 by forming ubiquitin ligase complexes with TRIM28.	SIGNOR-267593
Q04759	P15407	1	phosphorylation	up-regulates activity	0.2	PKCθ-induced phosphorylations, in part at T217 and T227 residues, strongly and specifically increased Fra-1 transcriptional activity through the stimulation of Fra-1 transactivation domain, without affecting JUN factors.	SIGNOR-260879
P42768	P06241	0	phosphorylation	up-regulates activity	0.561	As shown in XREF_FIG F, Fyn immunoprecipitates from activated T cells induced the tyrosine phosphorylation of WASp, but neither WASpDeltaPro nor WASpY291F mutant proteins were phosphorylated in this assay.	SIGNOR-279333
Q13546	Q6GQQ9	0	deubiquitination	down-regulates activity	0.538	NF-kappaB Suppression by the Deubiquitinating Enzyme Cezanne\|Our study provides several lines of evidence to suggest that Cezanne suppresses TNFR signaling to NF-κB by targeting RIP1 for deubiquitination.	SIGNOR-268411
P46531	Q06330	2	binding	up-regulates	0.95	The intracellular part of the notch receptor is cleaved off and translocates to the nucleus, where it binds to the transcription factor rbp-j.	SIGNOR-183510
P23760	P50221	2	binding	up-regulates activity	0.422	We show that Mox1 and Mox2 proteins are capable of interacting with Pax1 and Pax3. We propose that the Mox family of homeodomain proteins participates in the molecular signaling network regulating the diverse events of somite development through the physical interaction with the Pax1 and Pax3 members of the Pax family.	SIGNOR-222235
P49674	Q9UJU2	1	phosphorylation	down-regulates	0.268	Here, we identify ck1 and ck2 as major kinases that directly bind to and phosphorylate lef-1 inducing distinct, kinase-specific changes in the lef-1/dna complex.CK1-dependent phosphorylation inhibits, whereas ck2 activates lef-1/beta-catenin transcriptional activity in reporter gene assays.	SIGNOR-134497
Q8NHG7	Q9Y468	2	binding	down-regulates activity	0.2	In response to DNA damage, VCP/p97, an ATPase which unfolds proteins, removes L3MBTL1 from H4K20me2, creating free H4K20me2 for 53BP1 to bind to (Fig. 3b).	SIGNOR-262060
P55085	P35030	0	cleavage	up-regulates activity	0.388	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-263604
Q00535	P12830	1	phosphorylation	down-regulates activity	0.298	Using both the Cdk inhibitor roscovitine and an RNA interference strategy, it was also demonstrated that Cdh1 was phosphorylated by Cdk5, an enzyme that can be persistently activated when bound to p25 [ xref ], the proteolytic product of p35 that has previously been shown to accumulate in the neurons of patients with Alzheimer\u2019s disease [ xref ].	SIGNOR-279679
Q99835	P00450	2	binding	down-regulates	0.2	Genetic and biochemical studies imply that smo can adopt an active conformation but that it is normally repressed by patched (ptch), a 12-transmembrane protein considered the receptor for hh	SIGNOR-148451
Q96Q42	P51149	2	binding	down-regulates activity	0.305	The absence of active Rab7 prolongs ALS2presence and Rab5 activation on macropinosomes, indicating that activeRab7 is necessary for Rab5 inactivation through ALS2 dissociation and playskey roles in the Rab switch on macropinosomes. Taken together, active Rab7is necessary for Rab5 down-regulation through ALS2dissociation, thereby acting as a central component inthe Rab5-to-Rab7 switch in macropinocytosis	SIGNOR-277778
P43378	P46459	1	dephosphorylation	down-regulates	0.413	Our results suggest that the molecular mechanism by which ptp-meg2 promotes secretory vesicle fusion involves the local release of nsf from a tyrosine-phosphorylated, inactive state.	SIGNOR-128348
P01019	P12821	0	cleavage	up-regulates activity	0.782	Angiotensin I-converting enzyme is a zinc metallopeptidase that plays an important role in blood pressure regulation by cleaving the inactive decapeptide angiotensin I to angiotensin II, a potent vasopressor octapeptide.	SIGNOR-253326
O96013	P18084	1	phosphorylation	up-regulates	0.451	Pak4 specifically phosphorylated the integrin beta5 subunit at ser-759 and ser-762 within the beta5-sers-motif. Point mutation of these two serine residues abolished the pak4-induced cell migration, indicating a functional role for these phosphorylations in migration.	SIGNOR-165702
P07333	P09603	2	binding	up-regulates activity	0.938	The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34)	SIGNOR-255568
Q9UJD0	Q9UFD9	2	binding	down-regulates activity	0.285	SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.	SIGNOR-264370
P27361	P06239	2	phosphorylation	up-regulates activity	0.566	Phosphorylation at Ser-59 (or alternatively, its mutation to Glu) reverses the inhibition and allows interaction of the p56lck SH2 domain with p62.\|phosphotyrosine-independent binding of p62 to the p56lck SH2 domain appears to provide an alternative pathway for p56lck signaling that is regulated by Ser-59 phosphorylation.	SIGNOR-249469
O95835	Q9H093	0	phosphorylation	down-regulates	0.307	Phosphorylation at ser-464 by nuak1 and nuak2 leads to decreased protein level and is required to regulate cellular senescence and cellular ploidy	SIGNOR-161796
P49841	P13807	1	phosphorylation	down-regulates activity	0.686	Glycogen synthase kinase-3 phosphorylates three serine residues on glycogen synthase (sites 3a, 3b and 3c) which are all located in the same nine-amino-acid segment of the polypeptide chain. The sequence in this region is: Arg-Tyr-Pro-Arg-Pro-Ala-Ser(P)-Val-Pro-Pro-Ser(P)-Pro-Ser-Leu-Ser(P)-Arg-.	SIGNOR-253007
Q9UHD9	P51991	2	binding	up-regulates quantity by stabilization	0.447	We screened a yeast two-hybrid library using the central domain of ubiquilin-2 hoping to identify proteins whose binding is affected by the UBQLN2 mutations.\|\|Additionally, our evidence that ubiquilin-2 is in- volved in stabilizing hnRNPA1 protein	SIGNOR-262272
Q14289	P49023	1	phosphorylation	down-regulates quantity by destabilization	0.94	P130Cas and paxillin can be phosphorylated by Fak or Pyk2, and bind directly to these kinases.	SIGNOR-279272
Q13283	Q14444	2	binding	up-regulates activity	0.588	Caprin-1 and G3BP-1 were directly or indirectly associated in a stable complex. The Caprin-1/G3BP-1 complex occurs in cytoplasmic RNA granules	SIGNOR-260982
P52630	Q00978	2	binding	up-regulates activity	0.921	Coimmunoprecipitation assays demonstrate p48 association with STAT2 but not STAT1.The studies demonstrate the in vivo existence of a STAT2.p48 complex and a distinct STAT2.STAT1 complex after IFN-alpha stimulation. Data suggest that distinct bipartite complexes STAT2.p48 and STAT2.STAT1 translocate to the nucleus and associate on the DNA target site as ISGF3.	SIGNOR-217806
P40189	P26441	2	binding	up-regulates	0.682	Stimulation of cells with the interleukin-6 family of cytokines triggers homo- or hetero-dimerization of gp130. The dimerization of gp130 leads to activation of associated cytoplasmic tyrosine kinases and subsequent modification of transcription factors. Some of these biological activities of il-6 are also often exerted by other cytokines, i.e. Il-11, lif, osm, cntf, and ct-2.	SIGNOR-47991
Q9HBW0	Q14344	2	binding	up-regulates	0.402	Lysophosphatidic acid (lpa), a major g protein coupled receptor (gpcr)-activating ligand present in serum, elicits growth factor like responses by stimulating specific gpcrs coupled to heterotrimeric g proteins such as g(i), g(q), and g12/13.	SIGNOR-135837
P53041	P48730	0	phosphorylation	up-regulates activity	0.333	Here, we show an "on/off switch" mechanism for PP5 regulation. The casein kinase 1δ (CK1δ) phosphorylates T362 in the catalytic domain of PP5, which activates and enhances phosphatase activity independent of Hsp90.	SIGNOR-277373
P21731-2	P17252	0	phosphorylation	down-regulates activity	0.521	These data suggest a model whereby agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling, profoundly desensitizing signalling, and promotes beta-arrestin association and, in turn, facilitates TPbeta internalization.	SIGNOR-274092
Q92995	Q86U44	0	post transcriptional regulation	up-regulates quantity by stabilization	0.2	Furthermore, N6-methyladenosine methyltransferase-like 3 (METTL3) mediated stabilization of USP13 mRNA that required the m6A reader IGF2BP2.	SIGNOR-275839
P49841	Q15418	0	phosphorylation	down-regulates	0.359	S6k then phosphorylates the same serine residue on gsk3 that is targeted by pkb/akt (fig. 1), thereby inhibiting its activity.	SIGNOR-110917
Q9UJU2	Q04725	2	binding	down-regulates	0.638	Mapping studies reveal that groucho/tle binds two regions in lef-1.	SIGNOR-185736
Q9UM11	P30304	1	ubiquitination	down-regulates quantity by destabilization	0.464	We found that Cdc25 A degradation during mitotic exit and in early G(1) is mediated by the anaphase-promoting complex or cyclosome (APC/C)(Cdh1) ligase, and that a KEN-box motif in the N-terminus of the protein is required for its targeted degradation.	SIGNOR-271388
O15360	Q13131	0	phosphorylation	up-regulates activity	0.332	FANCA was phosphorylated by AMPK at S347 and phosphorylation increased with MMC treatment. MMC-induced FANCD2 monoubiquitination and nuclear foci formation were compromised in a U2OS cell line that stably overexpressed the S347A mutant form of FANCA compared to wild-type FANCA-overexpressing cells, indicating a requirement for FANCA phosphorylation at S347 for proper activation of the FA/BRCA pathway.	SIGNOR-277264
P10636	Q16816	0	phosphorylation	down-regulates activity	0.313	Muscle phosphorylase kinase phosphorylates Ser237, Ser262, Ser285, Ser305, and Ser352 of human tau. in vitro phosphorylation of tau on Ser262 alone strongly reduced the ability of tau to bind microtubules whereas the phosphorylation of many Ser/Thr-Pro motif sites of tau showed moderate effects on the binding of tau to microtubules	SIGNOR-250285
Q9Y463	Q99801	1	phosphorylation	down-regulates quantity by destabilization	0.332	In addition, an in vitro kinase assay showed that DYRK1B phosphorylated NKX3.1 at serine 185, a residue critical for NKX3.1 steady-state turnover.	SIGNOR-279610
P27361	Q16204	1	phosphorylation	up-regulates activity	0.367	We have characterized the H4(D10S170) gene product, showing that it is a ubiquitously expressed 55 KDa nuclear and cytosolic protein that is phosphorylated following serum stimulation. This phosphorylation was found to depend on mitogen-activated protein kinase (MAPK) Erk1/2 activity and to be associated to the relocation of H4(D10S170) from the nucleus to the cytosol. S244 is the major target residue of ERK1	SIGNOR-276003
O60934	Q13535	0	phosphorylation	up-regulates	0.785	We demonstrate that mrn and atr/atr-interacting protein (trip) interact with each other, and the forkhead-associated/breast cancer c-terminal domains (fha/brct) of nbs1 play a significant role in mediating this interaction. Mutations in the fha/brct domains do not prevent atr activation but specifically impair atr-mediated nbs1 phosphorylation at ser-343, which results in a defect in the s-phase checkpoint.	SIGNOR-155214
Q99250	Q92913	2	binding	down-regulates activity	0.269	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-253427
Q9UKT4	P53350	0	phosphorylation	down-regulates	0.783	We propose that the balance of evi5 and polo-like kinase activities determines the timely accumulation of emi1 and cyclin, ensuring mitotic fidelity.	SIGNOR-142949
Q9UQD0	Q92913	2	binding	down-regulates activity	0.406	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-253411
Q9ULB1	P61764	2	binding	up-regulates activity	0.527	We propose that all these neurexin complexes can interact with Munc18. Both Mint1 and Mint2 could function as direct adaptors of Munc18 to neurexins, whereas Mint1 in addition could recruit Munc18 to CASK-neurexin (Fig. 5 B).	SIGNOR-264040
P04275	P09958	0	cleavage	up-regulates activity	0.481	Like PACE,PACE4 was able to process pro-vWF to its mature form, and efficient cleavage required both the P4 arginine and the P2 lysine	SIGNOR-260368
P41229	Q16665	0	transcriptional regulation	up-regulates quantity by expression	0.259	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-271564
Q99814	P29375	1	transcriptional regulation	up-regulates quantity by expression	0.265	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-271580
Q9GZT5	O75581	2	binding	up-regulates	0.56	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-131622
P12931	P55210	1	phosphorylation	up-regulates activity	0.395	Src enhances caspase-7 activity in vitro and in cells.\|When all four sites were mutated to phenylalanine, the in vitro kinase assay results showed that phosphorylation of the Mut-caspase-7 protein by Src decreased dramatically compared with Wt-caspase-7, suggesting that these four sites, Tyr58, Tyr151, Tyr229 and Tyr230, are the most important sites of caspase-7 to be phosphorylated by Src (XREF_FIG).	SIGNOR-278455
Q9Y4H4	P63096	2	binding	down-regulates activity	0.492	GPSM3 acts through its two GoLoco motifs to exert GDP dissociation inhibitor activity over Galpha(i) subunits\|interactions between GPSM3 and Galphai1 or Gbeta1 (20) was assayed by BRET.	SIGNOR-264864
P31749	P78527	0	phosphorylation	up-regulates activity	0.754	DNA-PK phosphorylates HM Ser473 of PKB. However, we also noted similar patterns in T loop Thr308 phosphorylation after _-IR []his function is apparently restricted to the PKBalpha isoform	SIGNOR-252431
Q12913	P40198	1	dephosphorylation	down-regulates activity	0.387	We also determined that recombinant PTPRJ directly dephosphorylates the cytoplasmic tyrosine residues of purified full-length CEACAM3 and recognizes synthetic CEACAM3-derived phospho-peptides as substrates.\|We show depletion of PTPRJ results in a gain-of-function phenotype, while overexpression of a constitutively active PTPRJ phosphatase strongly reduces bacterial uptake via CEACAM3.	SIGNOR-277091
O15297	O15151	1	dephosphorylation	up-regulates quantity by stabilization	0.431	PPM1D also inhibits p53 activity by dephosphorylating Ser395 and stabilizing MDM2 and by dephosphorylating Ser403 on MDMX	SIGNOR-275491
Q7LG56	P23921	2	binding	up-regulates activity	0.935	Taken together, we conclude that UV-induced activation of p53R2 transcription and binding of p53R2 to hRRM1 to form RR holoenzyme are impaired in the p53-mutant cell line PC3.	SIGNOR-259366
Q13976	Q13976	2	phosphorylation	up-regulates	0.2	Serines 64 and 79 are homologous residues that are juxtaposed to the autoinhibitory pseudosubstrate site in cgmp-dependent protein kinase type ialpha and type ibeta (pkg-ialpha and pkg-ibeta), respectively. Autophosphorylation of this residue is associated with activation of type i pkgs.	SIGNOR-89839
Q5BJH7	P08908	1	relocalization	up-regulates activity	0.399	Together, our results provide strong evidence that Yif1B is a member of the ER/Golgi trafficking machinery, which plays a key role in specific targeting of 5-HT(1A)R to the neuronal dendrites. This finding opens up new pathways for the study of 5-HT(1A)R regulation by partner proteins and for the development of novel antidepressant drugs.\|We confirmed 5-HT(1A)R-Yif1B interaction by glutathione S-transferase pull-down experiments using rat brain extracts and transfected cell lines.	SIGNOR-268299
P78317	P23511	2	binding	up-regulates activity	0.2	Coactivator RNF4 is involved in the GCH gene expression. Through serial deletion and mutagenesis studies of the GCH promoter, we defined the RNF4-responsive element on GCH proximal promoter as a CCAAT box. RNF4 did not possess specific DNA binding activity toward this CCAAT box, which suggests that RNF4 may be a coactivator of the CCAAT boxbinding protein nuclear factor Y (NF-Y). RNF4 is a coactivator for nuclear factor Y on GTP cyclohydrolase I proximal promoter.	SIGNOR-252229
P24941	P31749	0	phosphorylation	up-regulates	0.328	Akt phosphorylates cdk2 at threonine 39 residue both in vitro and in vivo. Although cdk2 threonine 39 phosphorylation mediated by akt enhances cyclin-a binding, it is dispensable for its basal binding and the kinase activity.	SIGNOR-178058
P55957	Q07812	2	binding	up-regulates	0.825	Bid, a bh3-domain-only protein which interacts with bax, was able to trigger a conformational change in bax.	SIGNOR-73902
P05112	P24394	2	binding	up-regulates	0.942	IL-4R Is a 140-kd protein that binds il-4 with high affinity	SIGNOR-100762

P05106

P49758

2

binding

down-regulates

0.2

Numb binds to integrin-betas and localizes to clathrin-coated structures

SIGNOR-156762

P48730

P51532

1

phosphorylation

down-regulates quantity by destabilization

0.2

We reveal that CK1δ phosphorylates Brg1 at Ser31/Ser35 residues to facilitate the binding of Brg1 to FBW7, leading to ubiquitination-mediated degradation.

SIGNOR-277407

P54646

Q96RR4

0

phosphorylation

up-regulates

0.619

These data indicate that the camkks function in intact cells as ampkks, predicting wider roles for these kinases in regulating ampk activity in vivo.

SIGNOR-138364

P45983

O95140

1

phosphorylation

down-regulates quantity

0.428

We demonstrate that a critical component of the mitochondrial fusion apparatus, the mitofusin Mfn2, is a target for phosphorylation in response to a variety of cellular stresses. We provide direct evidence that JNK mediates this phosphorylation.

SIGNOR-274138

Q13315

Q13535

0

phosphorylation

up-regulates activity

0.747

Atr-dependent phosphorylation and activation of atm in response to uv treatment or replication fork stalling. Here, we show that atm phosphorylation at ser1981, a characterised autophosphorylation site, is atr-dependent and atm-independent following replication fork stalling or uv treatment

SIGNOR-150870

Q9UKP6

P50148

2

binding

up-regulates activity

0.435

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-257377

P63000

O94988

0

gtpase-activating protein

down-regulates activity

0.435

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260502

O95644

Q14164

0

phosphorylation

up-regulates activity

0.2

Phosphorylation of NFATC1 at PIM1 target sites is essential for its ability to promote prostate cancer cell migration and invasion. Here we have identified ten PIM1 target sites in NFATC1 and found that prevention of their phosphorylation significantly decreases the transcriptional activity as well as the pro-migratory and pro-invasive effects of NFATC1 in prostate cancer cells.

SIGNOR-276778

P42568

O00141

0

phosphorylation

down-regulates activity

0.509

In addition to Nedd4-2, Sgk1 also phosphorylates Af9, forkhead like transcription factor FOXO3a and several other substrates.|Sgk1 impairs the ability of Af9 to interact with Dot1a at these subregions without impacting Af9 DNA binding activity, leading to targeted histone H3 K79 hypomethylation.

SIGNOR-279111

Q9BY66

P68431

1

demethylation

up-regulates activity

0.2

KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.

SIGNOR-264308

O75914

P04049

1

phosphorylation

up-regulates

0.556

The protein kinase pak3 positively regulates raf-1 activity through phosphorylation of serine 338.

SIGNOR-62043

Q9NRD1

O14757

2

binding

down-regulates quantity by destabilization

0.496

Here, we report that DNA damage not only activates Chk1, but also exposes a degron-like region at the carboxyl terminus of Chk1 to an Fbx6-containing SCF (Skp1-Cul1-F box) E3 ligase, which mediates the ubiquitination and degradation of Chk1 and, in turn, terminates the checkpoint.

SIGNOR-271879

Q14938

P23352

1

transcriptional regulation

down-regulates quantity

0.2

By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development

SIGNOR-268884

P25101

P08754

2

binding

up-regulates activity

0.434

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-257165

Q93097

O75197

2

binding

up-regulates

0.588

Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors andinitiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.

SIGNOR-131780

O14965

Q9UNN5

1

phosphorylation

down-regulates activity

0.2

This study reports that aurora-a (aur-a) phosphorylates fas-associated factor-1 (faf1) at ser-289 and ser-29 our findings support the negative feedback regulation of aur-a via phosphorylation of the death-promoting protein, faf1

SIGNOR-180891

O15182

O43303

2

binding

up-regulates activity

0.418

We report that CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo. our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis.

SIGNOR-265968

O96018

P61764

2

binding

up-regulates activity

0.501

Munc18-1 is a neuronal protein that interacts with syntaxin 1 and is required for synaptic vesicle exocytosis. We have now identified two Munc18-1-interacting proteins called Mint1 and Mint2 that may mediate the function of Munc18-1.

SIGNOR-264036

Q9BWP8

P48740

2

binding

up-regulates activity

0.622

On the basis of the significant concentration of CL-11 in circulation and CL-11's interaction with various microorganisms and MASP-1 and/or MASP-3, it is conceivable that CL-11 plays a role in activation of the complement system and in the defense against invading microorganisms.

SIGNOR-263409

P60520

Q13501

2

binding

up-regulates activity

0.862

P62 binds both to lc3a and -b and the related gabarap family proteins/this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguisha

SIGNOR-156307

Q99541

P35790

0

phosphorylation

down-regulates quantity by destabilization

0.2

In addition, as a protein kinase, CHKalpha2 phosphorylates PLIN2 at Tyrosine 232 and PLIN3 at Tyrosine 251. Phosphorylated PLIN2 and PLIN3 are separated from lipid droplets and degraded by Hsc70-mediated autophagy, thereby promoting lipid droplet lipolysis, fatty acid oxidation and glioblastoma growth

SIGNOR-267649

P41145

P01213

2

binding

up-regulates activity

0.668

We recently cloned a human kappa opioid receptor and stably expressed it in Chinese hamster ovary (CHO) cells. In this study, the effects of activation of the human kappa receptor by agonists on [35S]GTPgammaS binding to CHO cell membranes were examined.. The rank order of potencies of opioid ligands tested in stimulating [35S]GTPgammaS binding was dynorphin A 1-17 > (+/-)-ethylketocyclazocine > beta-funaltrexamine, (-)-U50,488H, tifluadom > nalorphine > pentazocine, nalbuphine > buprenorphine.

SIGNOR-258411

P08172

P63096

2

binding

up-regulates activity

0.511

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-256685

O75385

Q9Y2H1

0

phosphorylation

down-regulates quantity

0.2

STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination

SIGNOR-270348

P00519

Q13148

1

phosphorylation

up-regulates quantity

0.2

The phosphorylation of tyrosine 43 of TDP-43 by c-Abl led to increased TDP-43 levels in the cytoplasm and increased the formation of G3BP1-positive stress granules in SH-SY5Y cells.

SIGNOR-279135

Q8NFH5

P53350

0

phosphorylation

down-regulates activity

0.415

Collectively, these data show that mitotic hyperphosphorylation of Nup53 by CDK1 and PLK1 contributes to its removal from NPCs.|The combined mutation of the CDK1 and PLK1 sites to phosphomimetic residues almost completely abolished NPC integration of Nup53, indicating that hyperphosphorylation of Nup53 might be incompatible with its NPC association.

SIGNOR-279252

Q9NZI6

P06493

0

phosphorylation

up-regulates activity

0.2

In addition, overexpression of TFCP2L1 and CDK1 in T24 cells increased clonogenic activity in a clonogenic limiting dilution assay (Fig\u00a05H), confirming the importance of CDK1\u2010TFCP2L1 pathways for the stemness features of BC cells.High levels of co\u2010expression of p\u2010TFCP2L1 and CDK1 were associated with distant metastasis in our cohort of BC patients (Table\u00a01).|Tfcp2l1 Thr177 phosphorylation by CDK1 is essential for proliferation and cell cycle progression of ESCs.|Tfcp2l1 is phosphorylated at Thr177 by CDK1.

SIGNOR-278472

Q8N2Q7

Q9P2S2

2

binding

up-regulates activity

0.829

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

SIGNOR-264154

Q92793

Q00978

1

acetylation

up-regulates activity

0.361

CBP was also the most effective one among the acetyltransferases tested for catalyzing IRF9 acetylation in 293T cells. [²] Figure 5 (F) K81 acetylation is required for IRF9 dimerization between the N-terminal 1-118 and the C-terminal 340-393 regions. In the left panel, Myc-DBD (1- 118) of IRF9 was cotransfected with 118-393, 118-339, or 1-393 (FL) of IRF9 in 293T cells. Anti-IRF9 (C-terminal region) precipitates were analyzed with anti-Myc or anti-IRF9. Anti-IRF9 precipitates, prepared from 293T cells cotransfected with the C-terminal fragment 118-393 of IRF9 and Myctagged DBD of different forms, were analyzed with anti-Myc or anti-IRF9 (right panel).

SIGNOR-217787

Q04206

Q9Y618

1

relocalization

down-regulates activity

0.404

Furthermore, overexpression of Flt3-ITD led to a partial relocalization of SMRT protein from the nucleus to the cytoplasm. This indicates that shuttling of p65 was necessary for Flt3-ITD-mediated SMRT nuclear export.

SIGNOR-261539

Q5TCY1

P10636

1

phosphorylation

down-regulates

0.451

Direct tau phosphorylation by ttbk1 at ser198, ser199, ser202 and ser422, which are also phosphorylated in phfs. Ttbk1 also induces tau aggregation in human neuronal cells in a dose-dependent manner. We conclude that ttbk1 is a neuron-specific dual kinase involved in tau phosphorylation at ad-related sites and is also associated with tau aggregation.

SIGNOR-148970

O00744

Q14332

2

binding

up-regulates

0.64

Inhibition of adipogenesis by wnt10b is likely mediated by wnt receptors, frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor-related proteins 5 and 7

SIGNOR-89137

Q96M98

O60260

0

polyubiquitination

down-regulates quantity by destabilization

0.2

In this study, we found that CHIP promotes Parkin-mediated Pael-R ubiquitination and subsequent degradation. In vitro ubiquitination assays suggested that only a combination of both Parkin and its cofactor CHIP function as a ubiquitin ligase, which is able to sufficiently ubiquitinate Pael-R in vivo (Figure 6).

SIGNOR-272889

Q14432

P17252

0

phosphorylation

up-regulates

0.2

Protein kinase c-mediated phosphorylation and activation of pde3a regulate camp levels in human platelets. together, these results demonstrate that platelet activation stimulates pkc-dependent phosphorylation of pde3a on ser(312), ser(428), ser(438), ser(465), and ser(492) leading to a subsequent increase in camp hydrolysis and 14-3-3 binding.

SIGNOR-184452

Q15759

P10636

1

phosphorylation

down-regulates activity

0.341

Phosphorylation of tau by SAPK3 and SAPK4 resulted in a marked reduction in its ability to promote microtubule assembly.|Tau phosphorylated by SAPK2b and SAPK2a also reacted with AT8, whereas AT8 failed to recognise tau phosphorylated by SAPK1gamma.

SIGNOR-279637

P49810

Q96BI3

2

binding

up-regulates

0.923

Gamma secretase subunit. Leads to ps1/ps2 eterodimer complex stabilisation. By using co-immunoprecipitation and nickel affinity pull-down approaches, we now show that mammalian aph-1 (maph-1), a conserved multipass membrane protein, physically associates with nicastrin and the heterodimers of the presenilin amino- and carboxyl-terminal fragments in human cell lines and in rat brain.

SIGNOR-93265

O94768

Q15139

0

phosphorylation

up-regulates activity

0.252

Coexpression of DRAK2 and a constitutively active PKD mutant (CA-PKD1; PKD1-S738/742E) were sufficient to greatly enhance DRAK2 autophosphorylation, supporting the hypothesis that PKD catalytic activity promotes DRAK2 function.|We note that PKD was able to phosphorylate DRAK2 outside of its C terminus, suggesting that PKD mediated phosphorylation occurs on a site in the 1-290 fragment of DRAK2.

SIGNOR-279753

Q9UGL1

O00257

2

binding

up-regulates activity

0.399

Our results clearly showed that the PcG protein hPc2 interacted with the N-terminus of JARID1B both in vivo and in vitro. It is interesting that the C-terminus of hPc2 was essential for the interaction and transcriptional co-repression.

SIGNOR-226447

Q05655

Q01995

1

phosphorylation

down-regulates activity

0.327

Of the three consensus protein kinase C or casein kinase II phosphorylation sites in SM22, only Ser-181 was readily phosphorylated by protein kinase C in vitro, and such phosphorylation greatly decreased actin binding.

SIGNOR-249061

P53041

Q969Q6

2

binding

up-regulates activity

0.346

Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and function

SIGNOR-272480

Q8WZ64

P61586

1

gtpase-activating protein

down-regulates activity

0.514

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260453

P29597

Q13118

1

phosphorylation

down-regulates activity

0.438

These data strongly supported that Tyk2 phosphorylates TIEG1.|Tyrosine kinase Tyk2-mediated phosphorylation of TIEG1 at Tyr179 promoted noncanonical K-27-linked polyubiquitination, which inhibited TIEG1 nuclear translocation.

SIGNOR-279575

Q6ZNA4

O15105

1

ubiquitination

down-regulates

0.736

Axin is a scaffold protein in tgf-beta signaling that promotes degradation of smad7 by arkadia

SIGNOR-119666

Q13263

Q9UBF1

2

binding

up-regulates activity

0.505

In this study, we demonstrated that the tripartite motif-containing protein 28 (TRIM28) binds directly to and promotes FBP1 for ubiquitination and degradation. MAGE-A3 and MAGE-C2, which are known to be overexpressed in HCC, can enhance TRIM28-dependent degradation of FBP1 by forming ubiquitin ligase complexes with TRIM28.

SIGNOR-267593

Q04759

P15407

1

phosphorylation

up-regulates activity

0.2

PKCθ-induced phosphorylations, in part at T217 and T227 residues, strongly and specifically increased Fra-1 transcriptional activity through the stimulation of Fra-1 transactivation domain, without affecting JUN factors.

SIGNOR-260879

P42768

P06241

0

phosphorylation

up-regulates activity

0.561

As shown in XREF_FIG F, Fyn immunoprecipitates from activated T cells induced the tyrosine phosphorylation of WASp, but neither WASpDeltaPro nor WASpY291F mutant proteins were phosphorylated in this assay.

SIGNOR-279333

Q13546

Q6GQQ9

0

deubiquitination

down-regulates activity

0.538

NF-kappaB Suppression by the Deubiquitinating Enzyme Cezanne|Our study provides several lines of evidence to suggest that Cezanne suppresses TNFR signaling to NF-κB by targeting RIP1 for deubiquitination.

SIGNOR-268411

P46531

Q06330

2

binding

up-regulates

0.95

The intracellular part of the notch receptor is cleaved off and translocates to the nucleus, where it binds to the transcription factor rbp-j.

SIGNOR-183510

P23760

P50221

2

binding

up-regulates activity

0.422

We show that Mox1 and Mox2 proteins are capable of interacting with Pax1 and Pax3. We propose that the Mox family of homeodomain proteins participates in the molecular signaling network regulating the diverse events of somite development through the physical interaction with the Pax1 and Pax3 members of the Pax family.

SIGNOR-222235

P49674

Q9UJU2

1

phosphorylation

down-regulates

0.268

Here, we identify ck1 and ck2 as major kinases that directly bind to and phosphorylate lef-1 inducing distinct, kinase-specific changes in the lef-1/dna complex.CK1-dependent phosphorylation inhibits, whereas ck2 activates lef-1/beta-catenin transcriptional activity in reporter gene assays.

SIGNOR-134497

Q8NHG7

Q9Y468

2

binding

down-regulates activity

0.2

In response to DNA damage, VCP/p97, an ATPase which unfolds proteins, removes L3MBTL1 from H4K20me2, creating free H4K20me2 for 53BP1 to bind to (Fig. 3b).

SIGNOR-262060

P55085

P35030

0

cleavage

up-regulates activity

0.388

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-263604

Q00535

P12830

1

phosphorylation

down-regulates activity

0.298

Using both the Cdk inhibitor roscovitine and an RNA interference strategy, it was also demonstrated that Cdh1 was phosphorylated by Cdk5, an enzyme that can be persistently activated when bound to p25 [ xref ], the proteolytic product of p35 that has previously been shown to accumulate in the neurons of patients with Alzheimer\u2019s disease [ xref ].

SIGNOR-279679

Q99835

P00450

2

binding

down-regulates

0.2

Genetic and biochemical studies imply that smo can adopt an active conformation but that it is normally repressed by patched (ptch), a 12-transmembrane protein considered the receptor for hh

SIGNOR-148451

Q96Q42

P51149

2

binding

down-regulates activity

0.305

The absence of active Rab7 prolongs ALS2presence and Rab5 activation on macropinosomes, indicating that activeRab7 is necessary for Rab5 inactivation through ALS2 dissociation and playskey roles in the Rab switch on macropinosomes. Taken together, active Rab7is necessary for Rab5 down-regulation through ALS2dissociation, thereby acting as a central component inthe Rab5-to-Rab7 switch in macropinocytosis

SIGNOR-277778

P43378

P46459

1

dephosphorylation

down-regulates

0.413

Our results suggest that the molecular mechanism by which ptp-meg2 promotes secretory vesicle fusion involves the local release of nsf from a tyrosine-phosphorylated, inactive state.

SIGNOR-128348

P01019

P12821

0

cleavage

up-regulates activity

0.782

Angiotensin I-converting enzyme is a zinc metallopeptidase that plays an important role in blood pressure regulation by cleaving the inactive decapeptide angiotensin I to angiotensin II, a potent vasopressor octapeptide.

SIGNOR-253326

O96013

P18084

1

phosphorylation

up-regulates

0.451

Pak4 specifically phosphorylated the integrin beta5 subunit at ser-759 and ser-762 within the beta5-sers-motif. Point mutation of these two serine residues abolished the pak4-induced cell migration, indicating a functional role for these phosphorylations in migration.

SIGNOR-165702

P07333

P09603

2

binding

up-regulates activity

0.938

The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34)

SIGNOR-255568

Q9UJD0

Q9UFD9

2

binding

down-regulates activity

0.285

SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.

SIGNOR-264370

P27361

P06239

2

phosphorylation

up-regulates activity

0.566

Phosphorylation at Ser-59 (or alternatively, its mutation to Glu) reverses the inhibition and allows interaction of the p56lck SH2 domain with p62.|phosphotyrosine-independent binding of p62 to the p56lck SH2 domain appears to provide an alternative pathway for p56lck signaling that is regulated by Ser-59 phosphorylation.

SIGNOR-249469

O95835

Q9H093

0

phosphorylation

down-regulates

0.307

Phosphorylation at ser-464 by nuak1 and nuak2 leads to decreased protein level and is required to regulate cellular senescence and cellular ploidy

SIGNOR-161796

P49841

P13807

1

phosphorylation

down-regulates activity

0.686

Glycogen synthase kinase-3 phosphorylates three serine residues on glycogen synthase (sites 3a, 3b and 3c) which are all located in the same nine-amino-acid segment of the polypeptide chain. The sequence in this region is: Arg-Tyr-Pro-Arg-Pro-Ala-Ser(P)-Val-Pro-Pro-Ser(P)-Pro-Ser-Leu-Ser(P)-Arg-.

SIGNOR-253007

Q9UHD9

P51991

2

binding

up-regulates quantity by stabilization

0.447

We screened a yeast two-hybrid library using the central domain of ubiquilin-2 hoping to identify proteins whose binding is affected by the UBQLN2 mutations.||Additionally, our evidence that ubiquilin-2 is in- volved in stabilizing hnRNPA1 protein

SIGNOR-262272

Q14289

P49023

1

phosphorylation

down-regulates quantity by destabilization

0.94

P130Cas and paxillin can be phosphorylated by Fak or Pyk2, and bind directly to these kinases.

SIGNOR-279272

Q13283

Q14444

2

binding

up-regulates activity

0.588

Caprin-1 and G3BP-1 were directly or indirectly associated in a stable complex. The Caprin-1/G3BP-1 complex occurs in cytoplasmic RNA granules

SIGNOR-260982

P52630

Q00978

2

binding

up-regulates activity

0.921

Coimmunoprecipitation assays demonstrate p48 association with STAT2 but not STAT1.The studies demonstrate the in vivo existence of a STAT2.p48 complex and a distinct STAT2.STAT1 complex after IFN-alpha stimulation. Data suggest that distinct bipartite complexes STAT2.p48 and STAT2.STAT1 translocate to the nucleus and associate on the DNA target site as ISGF3.

SIGNOR-217806

P40189

P26441

2

binding

up-regulates

0.682

Stimulation of cells with the interleukin-6 family of cytokines triggers homo- or hetero-dimerization of gp130. The dimerization of gp130 leads to activation of associated cytoplasmic tyrosine kinases and subsequent modification of transcription factors. Some of these biological activities of il-6 are also often exerted by other cytokines, i.e. Il-11, lif, osm, cntf, and ct-2.

SIGNOR-47991

Q9HBW0

Q14344

2

binding

up-regulates

0.402

Lysophosphatidic acid (lpa), a major g protein coupled receptor (gpcr)-activating ligand present in serum, elicits growth factor like responses by stimulating specific gpcrs coupled to heterotrimeric g proteins such as g(i), g(q), and g12/13.

SIGNOR-135837

P53041

P48730

0

phosphorylation

up-regulates activity

0.333

Here, we show an "on/off switch" mechanism for PP5 regulation. The casein kinase 1δ (CK1δ) phosphorylates T362 in the catalytic domain of PP5, which activates and enhances phosphatase activity independent of Hsp90.

SIGNOR-277373

P21731-2

P17252

0

phosphorylation

down-regulates activity

0.521

These data suggest a model whereby agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling, profoundly desensitizing signalling, and promotes beta-arrestin association and, in turn, facilitates TPbeta internalization.

SIGNOR-274092

Q92995

Q86U44

0

post transcriptional regulation

up-regulates quantity by stabilization

0.2

Furthermore, N6-methyladenosine methyltransferase-like 3 (METTL3) mediated stabilization of USP13 mRNA that required the m6A reader IGF2BP2.

SIGNOR-275839

P49841

Q15418

0

phosphorylation

down-regulates

0.359

S6k then phosphorylates the same serine residue on gsk3 that is targeted by pkb/akt (fig. 1), thereby inhibiting its activity.

SIGNOR-110917

Q9UJU2

Q04725

2

binding

down-regulates

0.638

Mapping studies reveal that groucho/tle binds two regions in lef-1.

SIGNOR-185736

Q9UM11

P30304

1

ubiquitination

down-regulates quantity by destabilization

0.464

We found that Cdc25 A degradation during mitotic exit and in early G(1) is mediated by the anaphase-promoting complex or cyclosome (APC/C)(Cdh1) ligase, and that a KEN-box motif in the N-terminus of the protein is required for its targeted degradation.

SIGNOR-271388

O15360

Q13131

0

phosphorylation

up-regulates activity

0.332

FANCA was phosphorylated by AMPK at S347 and phosphorylation increased with MMC treatment. MMC-induced FANCD2 monoubiquitination and nuclear foci formation were compromised in a U2OS cell line that stably overexpressed the S347A mutant form of FANCA compared to wild-type FANCA-overexpressing cells, indicating a requirement for FANCA phosphorylation at S347 for proper activation of the FA/BRCA pathway.

SIGNOR-277264

P10636

Q16816

0

phosphorylation

down-regulates activity

0.313

Muscle phosphorylase kinase phosphorylates Ser237, Ser262, Ser285, Ser305, and Ser352 of human tau. in vitro phosphorylation of tau on Ser262 alone strongly reduced the ability of tau to bind microtubules whereas the phosphorylation of many Ser/Thr-Pro motif sites of tau showed moderate effects on the binding of tau to microtubules

SIGNOR-250285

Q9Y463

Q99801

1

phosphorylation

down-regulates quantity by destabilization

0.332

In addition, an in vitro kinase assay showed that DYRK1B phosphorylated NKX3.1 at serine 185, a residue critical for NKX3.1 steady-state turnover.

SIGNOR-279610

P27361

Q16204

1

phosphorylation

up-regulates activity

0.367

We have characterized the H4(D10S170) gene product, showing that it is a ubiquitously expressed 55 KDa nuclear and cytosolic protein that is phosphorylated following serum stimulation. This phosphorylation was found to depend on mitogen-activated protein kinase (MAPK) Erk1/2 activity and to be associated to the relocation of H4(D10S170) from the nucleus to the cytosol. S244 is the major target residue of ERK1

SIGNOR-276003

O60934

Q13535

0

phosphorylation

up-regulates

0.785

We demonstrate that mrn and atr/atr-interacting protein (trip) interact with each other, and the forkhead-associated/breast cancer c-terminal domains (fha/brct) of nbs1 play a significant role in mediating this interaction. Mutations in the fha/brct domains do not prevent atr activation but specifically impair atr-mediated nbs1 phosphorylation at ser-343, which results in a defect in the s-phase checkpoint.

SIGNOR-155214

Q99250

Q92913

2

binding

down-regulates activity

0.269

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-253427

Q9UKT4

P53350

0

phosphorylation

down-regulates

0.783

We propose that the balance of evi5 and polo-like kinase activities determines the timely accumulation of emi1 and cyclin, ensuring mitotic fidelity.

SIGNOR-142949

Q9UQD0

Q92913

2

binding

down-regulates activity

0.406

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-253411

Q9ULB1

P61764

2

binding

up-regulates activity

0.527

We propose that all these neurexin complexes can interact with Munc18. Both Mint1 and Mint2 could function as direct adaptors of Munc18 to neurexins, whereas Mint1 in addition could recruit Munc18 to CASK-neurexin (Fig. 5 B).

SIGNOR-264040

P04275

P09958

0

cleavage

up-regulates activity

0.481

Like PACE,PACE4 was able to process pro-vWF to its mature form, and efficient cleavage required both the P4 arginine and the P2 lysine

SIGNOR-260368

P41229

Q16665

0

transcriptional regulation

up-regulates quantity by expression

0.259

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-271564

Q99814

P29375

1

transcriptional regulation

up-regulates quantity by expression

0.265

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-271580

Q9GZT5

O75581

2

binding

up-regulates

0.56

Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.

SIGNOR-131622

P12931

P55210

1

phosphorylation

up-regulates activity

0.395

Src enhances caspase-7 activity in vitro and in cells.|When all four sites were mutated to phenylalanine, the in vitro kinase assay results showed that phosphorylation of the Mut-caspase-7 protein by Src decreased dramatically compared with Wt-caspase-7, suggesting that these four sites, Tyr58, Tyr151, Tyr229 and Tyr230, are the most important sites of caspase-7 to be phosphorylated by Src (XREF_FIG).

SIGNOR-278455

Q9Y4H4

P63096

2

binding

down-regulates activity

0.492

GPSM3 acts through its two GoLoco motifs to exert GDP dissociation inhibitor activity over Galpha(i) subunits|interactions between GPSM3 and Galphai1 or Gbeta1 (20) was assayed by BRET.

SIGNOR-264864

P31749

P78527

0

phosphorylation

up-regulates activity

0.754

DNA-PK phosphorylates HM Ser473 of PKB. However, we also noted similar patterns in T loop Thr308 phosphorylation after _-IR []his function is apparently restricted to the PKBalpha isoform

SIGNOR-252431

Q12913

P40198

1

dephosphorylation

down-regulates activity

0.387

We also determined that recombinant PTPRJ directly dephosphorylates the cytoplasmic tyrosine residues of purified full-length CEACAM3 and recognizes synthetic CEACAM3-derived phospho-peptides as substrates.|We show depletion of PTPRJ results in a gain-of-function phenotype, while overexpression of a constitutively active PTPRJ phosphatase strongly reduces bacterial uptake via CEACAM3.

SIGNOR-277091

O15297

O15151

1

dephosphorylation

up-regulates quantity by stabilization

0.431

PPM1D also inhibits p53 activity by dephosphorylating Ser395 and stabilizing MDM2 and by dephosphorylating Ser403 on MDMX

SIGNOR-275491

Q7LG56

P23921

2

binding

up-regulates activity

0.935

Taken together, we conclude that UV-induced activation of p53R2 transcription and binding of p53R2 to hRRM1 to form RR holoenzyme are impaired in the p53-mutant cell line PC3.

SIGNOR-259366

Q13976

2

phosphorylation

up-regulates

0.2

Serines 64 and 79 are homologous residues that are juxtaposed to the autoinhibitory pseudosubstrate site in cgmp-dependent protein kinase type ialpha and type ibeta (pkg-ialpha and pkg-ibeta), respectively. Autophosphorylation of this residue is associated with activation of type i pkgs.

SIGNOR-89839

Q5BJH7

P08908

1

relocalization

up-regulates activity

0.399

Together, our results provide strong evidence that Yif1B is a member of the ER/Golgi trafficking machinery, which plays a key role in specific targeting of 5-HT(1A)R to the neuronal dendrites. This finding opens up new pathways for the study of 5-HT(1A)R regulation by partner proteins and for the development of novel antidepressant drugs.|We confirmed 5-HT(1A)R-Yif1B interaction by glutathione S-transferase pull-down experiments using rat brain extracts and transfected cell lines.

SIGNOR-268299

P78317

P23511

2

binding

up-regulates activity

0.2

Coactivator RNF4 is involved in the GCH gene expression. Through serial deletion and mutagenesis studies of the GCH promoter, we defined the RNF4-responsive element on GCH proximal promoter as a CCAAT box. RNF4 did not possess specific DNA binding activity toward this CCAAT box, which suggests that RNF4 may be a coactivator of the CCAAT boxbinding protein nuclear factor Y (NF-Y). RNF4 is a coactivator for nuclear factor Y on GTP cyclohydrolase I proximal promoter.

SIGNOR-252229

P24941

P31749

0

phosphorylation

up-regulates

0.328

Akt phosphorylates cdk2 at threonine 39 residue both in vitro and in vivo. Although cdk2 threonine 39 phosphorylation mediated by akt enhances cyclin-a binding, it is dispensable for its basal binding and the kinase activity.

SIGNOR-178058

P55957

Q07812

2

binding

up-regulates

0.825

Bid, a bh3-domain-only protein which interacts with bax, was able to trigger a conformational change in bax.

SIGNOR-73902

P05112

P24394

2

binding

up-regulates

0.942

IL-4R Is a 140-kd protein that binds il-4 with high affinity

SIGNOR-100762