GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P05114	P68400	phosphorylation	down-regulates	0.2	Protein kinases that phosphorylate hmg-14 17 at the major sites have been implicated from previous in vitro studies. Protein kinase c and a similar calcium phospholipid-dependent kinase have been reported to phosphorylate both proteins in vitro, where the phosphorylation of hmg-17 occurs predominantly at ser24 and to a lesser degree at ser28. Phosphorylation of hmg-14 at ser6 by camp- or cgmp-dependent kinases has also been reported. Thus, other kinases may contribute to phosphorylation at ser6 in response to oa. Ser88 and ser98 on hmg-14 are also phosphorylated by casein kinase ii in vitro. we conclude that the correlation we observe reflects a causal relationship, in which phosphorylation somehow facilitates the redistribution of hmg-14 and -17 toward non-nuclear pools.	SIGNOR-76274
Q9H0Z9	P49841	phosphorylation	down-regulates	0.2	Here, we showed that rnpc1 is phosphorylated at ser195 by glycogen synthase kinase 3 (gsk3). We also provided evidence that ser195 phosphorylation converts rnpc1 from a repressor to an activator of p53.	SIGNOR-203011
P31995	P07948	phosphorylation	up-regulates activity	0.2	Fyn and Blk definitely phosphorylate Y-282 in the ITAM of FcgRIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addition to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation	SIGNOR-262676
P09488	P10242	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
P35568	P17612	phosphorylation	down-regulates quantity by destabilization	0.2	Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223	SIGNOR-235675
Q96F46	P49840	phosphorylation	down-regulates quantity by destabilization	0.2	Glycogen synthase kinase 3 (GSK3) constitutively bound to and phosphorylated IL-17RA at T780, leading to ubiquitination and proteasome-mediated degradation of IL-17RA, thus inhibiting IL-17-mediated inflammation.	SIGNOR-277206
O95644	Q14164	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
P49959	Q9NRR5	binding	up-regulates activity	0.2	These data suggest that MRE11 is one of probably many UBQLN4 interaction partners. >Particularly HRR is dependent on ATM activity (Dietlein et al., 2014). Here, we showed that UBQLN4 is an ATM substrate and that DSB sealing is markedly impaired in UBQLN4-depleted cells. HRR depends on a 5′-3′ DSB end resection, which is initiated by the MRE11 nuclease	SIGNOR-265077
P46937	Q01538	transcriptional regulation	down-regulates quantity by repression	0.2	Myt1 and Myt1l transcription factors limit proliferation in GBM cells by repressing YAP1 expression. Examination of the gene expression changes in cells expressing Myt1 or Myt1l suggests that both repress expression of the YAP1 transcriptional coactivator, which functions primarily in the Hippo signaling pathway. Expression of YAP1 and its target genes is reduced in Myt-expressing cells, and there is an inverse correlation between YAP1 and MYT1/MYT1L expression in human brain cancer datasets. Together, our data suggest that Myt1 and Myt1l directly repress expression of YAP1, a protein which promotes proliferation and GBM growth.	SIGNOR-266777
O14649	Q13464	phosphorylation	down-regulates	0.2	Task1 channels contain two putative rho kinase phosphorylation sites, ser(336) and ser(393) . Mutation of ser(393) rendered task1 channels insensitive to et(a) - or et(b)-mediated current inhibition. In contrast, removal of ser(336) selectively attenuated et(a) -dependent task1 regulation without affecting the et(b) pathway.	SIGNOR-176025
P53539	P59595	transcriptional regulation	up-regulates quantity by expression	0.2	The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well	SIGNOR-260728
P17931	P42684	phosphorylation	up-regulates	0.2	The sh (src homology)3 domains of c-abl/arg bind to a p(80)gppsgp motif of gal3, and tyr79 and tyr118 are the major tyrosine phosphorylation sites. A consequence of this interaction and phosphorylation is the significant impairment of chaperone-mediated autophagy of gal3.	SIGNOR-163747
A2RUS2	Q8IYT8	phosphorylation	up-regulates activity	0.2	ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12.	SIGNOR-264733
P84243	Q9NRC8	deacetylation	up-regulates activity	0.2	SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation.\|Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression.	SIGNOR-275872
Q96QV6	Q14493	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265401
Q6FI13	Q86Y13	monoubiquitination	up-regulates activity	0.2	2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.	SIGNOR-271755
Q9BU19	Q13131	phosphorylation	down-regulates	0.2	Arebp is phosphorylated at ser(470) by ampk. Phosphorylation reduces the dna-binding activity of arebp.	SIGNOR-150590
P20671	Q86Y13	monoubiquitination	up-regulates activity	0.2	2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.	SIGNOR-271753
P84103	O15355	dephosphorylation	down-regulates activity	0.2	Here, we found that the PPM1G regulated SRSF3, and high levels of PPM1G decreased SRSF3 activity in HCC cells.\|PPM1G interacted with SRSF3 and dephosphorylated SRSF3.	SIGNOR-277048
P04062	Q9NR19	transcriptional regulation	up-regulates quantity by expression	0.2	Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy\|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1\|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants	SIGNOR-276552
P43629	P68400	phosphorylation	up-regulates quantity by stabilization	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. It seems that phosphorylation of 3DL1 by CK does not significantly affect receptor inhibitory function or turnover, at least in the assays that we have used so far.	SIGNOR-276077
P09471	P08912	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257009
P52948	P59634	binding	down-regulates activity	0.2	Orf6 of SARS-CoV antagonizes host interferon signaling by perturbing nuclear transport, and the NUP98-RAE1 interaction with Orf6 may perform the same function for SARS-CoV-2.	SIGNOR-260976
Q96T58	Q13153	phosphorylation	down-regulates activity	0.2	Pak1 phosphorylation sites in SHARP were mapped to Ser3486 and Thr3568 within the SHARP repression domain.	SIGNOR-278968
Q9Y618	Q9UQM7	phosphorylation	down-regulates	0.2	We demonstrated that camkii directly bound and phosphorylated smrt at ser-1407, thereby facilitating smrt translocation from the nucleus to the cytoplasm and proteasome-dependent degradation.	SIGNOR-191773
O43251	O14920	phosphorylation	up-regulates activity	0.2	Phosphorylation of RTA by IKKbeta increases RTA transcriptional activity and consequently viral mRNA production.	SIGNOR-279336
P63092	P25103	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256776
Q8WUI4	O94806	phosphorylation	up-regulates activity	0.2	Histone deacetylase (HDAC) 5 and 7, two members of the class II of classical HDAC [62], are in vivo substrates of PKD3 and PKD [63]. In response to a variety of signals, including phorbol esters, T cell receptor engagement, vascular endothelial growth factor and angiotensin stimulation, the activity of HDAC5 and 7 are regulated by a mechanism that involves PKD3 and PKD-mediated phosphorylation of the highly conserved Ser259 and Ser498 residues that are located in N-terminus of class II HDACs [63–67].	SIGNOR-275934
Q96PD2	P00519	phosphorylation	up-regulates activity	0.2	SFKs and Abl differentially phosphorylate DCBLD1 and DCBLD2 at distinct tyrosine phosphorylation sites.\|We report that Src family kinases and Abl differentially promote the interaction between the CRKL-SH2 domain and DCBLD1 and DCBLD2, and while Src family kinases and Abl each promote DCBLD1 and DCBLD2 binding to the CRKL-SH2 domain, the effect of Abl is more pronounced for DCBLD1. 45999997={Domain=45999998 LikeProtein=1399} 45999998="sh2 domain" 45999999="sh2 domain"}	SIGNOR-280167
P08754	Q9HC97	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256860
Q00987	Q96GD0	dephosphorylation	down-regulates activity	0.2	Considering the roles of NF2 in actin dynamics and Mdm2 regulation - , , , it is noteworthy to elucidate whether interaction of PLPP and CIN with NF2 modulates actin dynamics and Mdm2 degradation in neuronal excitability.\|Recently, we have reported that PLPP and CIN dephosphorylates Mdm2 at S166 site in activity dependent manners, which inhibits Mdm2 mediated PSD95 degradation by facilitating Mdm2 ubiquitination 38.	SIGNOR-277151
Q0VAM2	Q8TBJ4	binding	up-regulates activity	0.2	Oncogenic effects of imbalanced PRG3 are mediated via PRG3-RasGEF1 interaction and Ras activation. PRG3 interacts with RasGEF1 in vivo.We could further show that PRG3 executes the binding to RasGEF1 predominantly via its C-terminal domain (CT) and in the consequence causes Ras activation.	SIGNOR-261806
O15054	Q99814	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-271586
Q16695	Q92830	acetylation	down-regulates activity	0.2	The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.	SIGNOR-269604
P61587	P17252	phosphorylation	down-regulates activity	0.2	PKCalpha dependent Rnd3 phosphorylation downregulates Rnd3 inhibitory activity and leads to increased signaling through the Rho-ROCK pathway.\|We further show that PKC\u03b1 directly phosphorylates Rnd3 in an in vitro kinase assay.	SIGNOR-279557
O75385	P17252	phosphorylation	down-regulates activity	0.2	ULK1 is phosphorylated by PKCalpha at S423 in vivo and in vitro.\|PKC\u03b1 phosphorylation of ULK1 does not change its kinase activity	SIGNOR-279558
P48995	Q05655	phosphorylation	up-regulates activity	0.2	Taken together, these results indicate that store depletion induces interactions between TRPC1 and PKC\u03b4 in VSMCs, and that these interactions cause PKC\u03b4\u2010dependent phosphorylation of TRPC1.	SIGNOR-279559
P12755	O14965	phosphorylation	down-regulates quantity by destabilization	0.2	Here we show that AURKA phosphorylates in vitro the transcripcional co-repressor Ski on aminoacids Ser326 and Ser383. Phosphorylations on these aminoacids decreased Ski protein half-life	SIGNOR-276917
P07766	Q9UJZ1	binding	up-regulates activity	0.2	We observed that SLP-2 steadily associated with the CD3-epsilon chain of the TCR complex under resting conditions and during the 60 min of stimulation\|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-260375
Q8IVS8	Q9UNE7	ubiquitination	down-regulates quantity by destabilization	0.2	Mechanistically, glucose deprivation-activated ERK1 phosphorylates GLYCTK2 at serine 220 directly, which prevents STUB1 (ubiquitin E3 ligase) binding, thereby abrogating the ubiquitination and degradation of GLYCTK2. ERK1 phosphorylates GLYCTK2 at S220 to promotes its stability	SIGNOR-280258
P17252	Q13043	phosphorylation	up-regulates activity	0.2	Mst1 and Mst2 activate PKC\u03b1 to disrupt the LyGDI-Rac complex.\|Thus, the phosphorylation of PKC\u03b1 at Ser226 and Thr228 by Mst1 and Mst2 is required for the optimal activation of PKC\u03b1.	SIGNOR-280146
Q9UMX1	Q8TBB1	ubiquitination	down-regulates quantity	0.2	Indeed, they target different lysine residues in the SuFu protein, as LNX1 ubiquitinates SuFu at K59 and K470, and SCF Fbxl17 acts at K257, while Itch ubiquitinates at K321 and K457.\|XREF_FIG, ectopic LNX1 expression reduced SuFu protein levels in HEK-293T cells, while shRNA mediated knockdown of LNX1 increased these levels.	SIGNOR-278626
Q8N884	P51451	phosphorylation	down-regulates activity	0.2	DNA damage induces nuclear translocation of cGAS in a manner that is dependent on importin-α, and the phosphorylation of cGAS at tyrosine 215-mediated by B-lymphoid tyrosine kinase-facilitates the cytosolic retention of cGAS.	SIGNOR-275844
Q9Y5G1	Q9Y5I2	binding	up-regulates activity	0.2	The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.	SIGNOR-265707
P35236	P24723	phosphorylation	up-regulates activity	0.2	HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.	SIGNOR-276049
P07711	Q9UNZ2	binding	down-regulates activity	0.2	The SEP domain of p47 acts as a reversible competitive inhibitor of cathepsin L.	SIGNOR-265043
P19532	Q00534	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 .\|CDK4 and CDK6 phosphorylate TFEB and TFE3.	SIGNOR-279517
Q04206	Q9P286	phosphorylation	up-regulates activity	0.2	PAK5-mediated phosphorylation and nuclear translocation of NF-κB-p65 promotes breast cancer cell proliferation in vitro and in vivo\|We characterized that PAK5 could promote the phosphorylation and the nuclear translocation of p65 subunit of nuclear factor-kappaB, and demonstrated that p65 could directly bind to the promoter of Cyclin D1	SIGNOR-275657
Q9BYB0	P28482	phosphorylation	down-regulates activity	0.2	Interestingly, we discovered that several kinases in the MEK and ERK2 pathway destabilize Shank3 and that genetic deletion and pharmacological inhibition of ERK2 increases Shank3 abundance in vivo.\|We also determined that phosphorylation of Shank3 by ERK2 at selective residues promotes its ubiquitination and degradation.	SIGNOR-279538
Q12791	P17252	phosphorylation	up-regulates	0.2	Results showed that mutating s1076 altered the effect of pkc activation on bk(ca) channels in hek-293 cells	SIGNOR-186755
Q13470	Q7KZI7	phosphorylation	down-regulates activity	0.2	We also discover a MARK-mediated phosphorylation on TNK1 at S502 that promotes an interaction between TNK1 and 14-3-3, which sequesters TNK1 and inhibits its kinase activity.Phosphorylation of TNK1 at S502 within the proline rich domain is required for TNK1 binding to 14-3-3.MARKs mediate phosphorylation at S502 and 14-3-3 binding to TNK1, which restrains the movement of TNK1 into heavy membrane-associated clusters.	SIGNOR-273867
P35222	Q9NQU5	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
P10588	Q05655	phosphorylation	down-regulates	0.2	Ser-83 on recombinant nr2f6is a pkc substrate site;mutation of ser-83 (but not ser-89) to alanine strongly reduced pkc-mediated nr2f6 phosphorylation, confirming ser-83 as the major pkc phosphorylation site in nr2f6;the dna-binding capacity of nr2f6 is antagonized by a (p)ser-83 switch on nr2f6.	SIGNOR-180017
Q9NWD9	P53350	phosphorylation	up-regulates activity	0.2	In addition, the inhibition of PLK1 activity by BI2536 treatment sharply reduced BEX4 protein, which was localized at the centrosomes in the HeLa cells or the GFP-BEX4 stable cell lines.\|PLK1 directly phosphorylates BEX4 at T107 and contributes to BEX4-induced aneuploidy.	SIGNOR-279550
P35916	O43915	binding	up-regulates	0.2	Vegf-d is a ligand for both vegf receptors (vegfrs) vegfr-2 (flk1) and vegfr-3 (flt4) and can activate these receptors.	SIGNOR-55065
Q15054	P17612	phosphorylation	down-regulates	0.2	In this study, we identified s458, located in the pcna-interacting protein (pip-box) motif of p68, as a phosphorylation site for pka. Phosphomimetic mutation of s458 resulted in a decrease in p68 affinity for pcna as well as the processivity of pol _.	SIGNOR-195203
P19532	P11802	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
Q04760	P12931	phosphorylation	up-regulates activity	0.2	We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).	SIGNOR-276189
Q587J8	Q13315	phosphorylation	up-regulates activity	0.2	Notably, we identified two critical residues, Thr145 and Thr156, whose phosphorylation by Ataxia-telangiectasia mutated (ATM) is essential for KHDC3L's functions.	SIGNOR-273505
Q7Z2W7	P17612	phosphorylation	up-regulates activity	0.2	Using specific pharmacological and molecular tools combined with patch-clamp current recordings, we found that in heterologously expressed HEK-293 (human embryonic kidney) cells, TRPM8 channel is inhibited by the G(i) protein/adenylate cyclase (AC)/cAMP/protein kinase A (PKA) signaling cascade. We further identified the TRPM8 S9 and T17 as two key PKA phosphorylation sites regulating TRPM8 channel activity. the intracellular serine/threonine protein phosphatase 2A (PP2A) dephosphorylates TRPM8 Ser-9 and Thr-17 inhibiting the channel activity.	SIGNOR-273791
P38405	Q99500	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256933
P63092	P55085	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256752
P19086	Q15391	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257118
P17096	Q13315	phosphorylation	up-regulates activity	0.2	21 As shown in Fig. 2 b, ATM was able to phosphorylate in vitro the C-terminal peptide of HMGA1.	SIGNOR-279493
P27707	Q13535	phosphorylation	up-regulates activity	0.2	Since activation of dCK by IR was not prevented by KU-60019 at longer times, but could be suppressed if the ATR inhibitor was combined with the ATM inhibitor, we propose that dCK is activated by ATR when ATM is inhibited.\|Taken together, these data indicate that ATR, like ATM [15], can directly phosphorylate dCK at Ser 74 in vitro and thereby increase its activity.Most dCK activators share the feature of inducing DNA damage followed by DNA damage response, a complex signaling network aimed to preserve genome integrity.	SIGNOR-279494
P02671	P50281	cleavage	down-regulates quantity by destabilization	0.2	Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII\| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.\|MMP-14 27YVATRDN g-chain\| 105XDAATLKSR g-chain \| 92LTYNPDES g-chain \|105LTTNIXEXL a-chain\|433LVTSKGDKE a-chain\| 117FXSANNRD a-chain	SIGNOR-263620
Q86WV6	Q9C029	ubiquitination	down-regulates quantity by destabilization	0.2	RNF90 promoted K48-linked ubiquitination of MITA and its proteasome-dependent degradation.\|Finally, in vitro ubiquitination assays suggested that RNF90 promoted the ubiquitination of MITA directly (Fig 5E and 5F).	SIGNOR-278678
Q96A54	P25098	phosphorylation	down-regulates activity	0.2	AdipoR1 is Directly Phosphorylated by GRK2.\|In summary, our study demonstrates for the first time that cardiometabolic-regulatory, anti-inflammatory, and cardioprotective functions of APN are significantly impaired by GRK2 mediated AdipoR1 phosphorylative desensitization during a critical period of post-MI HF development.	SIGNOR-279463
P68431	Q9NRC8	deacetylation	up-regulates activity	0.2	SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation.\|Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression.	SIGNOR-275874
P38398	Q00341	binding	up-regulates activity	0.2	We show that vigilin interacts with the DNA damage response (DDR) proteins RAD51 and BRCA1, and vigilin depletion impairs their recruitment to DSB sites.	SIGNOR-266698
Q969R2	P48729	phosphorylation	up-regulates activity	0.2	CK1a1, JNK1 and CDK1 had the highest site-specific activity for ORP4L, while CDK1, GSK3a, CK1a1 and GSK3b showed the highest specificity for the site when corrected for background activity with ORP4L-S4A. Because of the complexity of the serine/proline-rich site, we did not determine which serine(s) in ORP4L were phosphorylated by candidate kinases.\|We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes.	SIGNOR-264877
P05230	Q05655	phosphorylation	up-regulates quantity	0.2	Translocated FGF1 can be phosphorylated by PKC\u03b4 on serine 130.	SIGNOR-278451
Q9Y4G8	P48729	phosphorylation	down-regulates quantity by destabilization	0.2	Here, we report that in response to factors that promote cell motility, the Rap guanine exchange factor RAPGEF2 is rapidly phosphorylated by I-kappa-B-kinase-β and casein kinase-1α and consequently degraded by the proteasome via the SCF(βTrCP) ubiquitin ligase.	SIGNOR-276604
Q9H2S1	P17612	phosphorylation	down-regulates	0.2	Mutagenesis and mass spectrometry studies identified four pka phosphorylation sites: ser465 (minor site) and three amino acid residues ser568, ser569, and ser570 (major sites) within the carboxyl-terminal region. pka activation decreased sk2 surface localization	SIGNOR-145040
O95379	P63096	binding	up-regulates activity	0.2	TNFAIP8: a new effector for Galpha(i) coupling to reduce cell death and induce cell transformation	SIGNOR-256491
P35236	Q02156	phosphorylation	up-regulates activity	0.2	HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.	SIGNOR-276050
P07355	P07947	phosphorylation	up-regulates activity	0.2	Activated YES1 interacts with ANXA2 andphosphorylates ANXA2 at Tyr24 site that induces ANXA2 activation and increases ANXA2 nuclear distribution , leading to activation of the tumorpromoting transcription factors ( such as Myc , Stat3 , Stat6 ) that promotes GC invasion and metastasis .\|YES1 phosphorylates ANXA2 at Tyr24 site that leads to ANXA2 activation and increased ANXA2 nuclear distribution.	SIGNOR-279435
Q15121	Q9UQM7	phosphorylation	up-regulates	0.2	Pea-15 is a phosphoprotein containing a ser-104 phosphorylated by protein kinase c and a ser-116 phosphorylated by camkii (calcium/calmodulin-dependent protein kinase ii) or akt. Phosphorylation of ser-104 is implicated in the regulation of glucose metabolism, while phosphorylation at ser-116 is required for pea-15 recruitment to the disc (death-initiation signalling complex)	SIGNOR-137614
Q8WUX9	P06493	phosphorylation	down-regulates activity	0.2	We found that recombinant CHMP7 could be directly phosphorylated by CDK1/CCNB1 in vitro and that CDK1-phosphorylation reduced the capacity of CHMP7 to sediment (Figure 4A and B).\|We identified direct CDK1 phosphorylation of CHMP7 at Ser3 and Ser441 as a suppressor of both CHMP7\u2019s ability to interact with LEM2 and its ability to assemble, as judged by sedimentation assays.	SIGNOR-279445
Q9UKT5	P49841	phosphorylation	up-regulates	0.2	Gsk3beta-mediated phosphorylation of fbx4 ser12 during the g1/s transition regulates fbx4 dimerization, which in turn governs fbx4-driven e3 ligase activity.	SIGNOR-171648
Q13200	Q9P1W9	phosphorylation	up-regulates activity	0.2	Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B).	SIGNOR-273896
P51608	O15111	phosphorylation	up-regulates activity	0.2	Representative confocal micrographs of 4th day differentiating cultures are shown. (C) IKK\u03b1 promotes MeCP2-dependent BDNF expression.\|The characterization of IKK\u03b1-mediated phosphorylation of MeCP2 at Ser421 and other residues and their effects on the activity of MeCP2 is a topic of current work in our laboratory.	SIGNOR-279459
P63215	Q99835	binding	up-regulates	0.2	Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling.	SIGNOR-148598
O75420	Q92600	binding	up-regulates activity	0.2	Through interaction analysis of RQCD1 with full-length or partial proteins of GIGYF1 and GIGYF2, segments corresponding to 620-665th and 667-712th amino acids were identified as potential interacting regions on GIGYF1 and GIGYF2, respectively, with RQCD1. we found that RQCD1 was required for enhancement of the interaction of Grb10 with GIGYF1 and GIGYF2	SIGNOR-260059
Q93096	P30291	phosphorylation	down-regulates activity	0.2	In this study , we found that WEE1 phosphorylates PRL1 and promotes PRL1 degradation .\|In this study, we demonstrated that WEE1 phosphorylates and inhibits PRL1 to regulate alternative splicing of CYCD1;1 and CYCD3;1 , which may represent a new cell cycle control mechanism.	SIGNOR-278434
Q8NER1	Q00535	phosphorylation	up-regulates activity	0.2	TNF-alpha overexpression increased Cdk5-mediated phosphorylation of TRPV1 at T407.\|These results suggest that the activation of Cdk5 by p35 enhances the response of TRPV1 to capsaicin, probably by phosphorylation of the channel [34].	SIGNOR-278437
O43236	O15033	ubiquitination	down-regulates quantity by destabilization	0.2	Furthermore, the ubiquitination and degradation of SMAC, HtrA2, and ARTS were significantly enhanced in AREL1-expressing cells following apoptotic stimulation, indicating that AREL1 binds to and ubiquitinates cytosolic but not mitochondria-associated forms of IAP antagonists	SIGNOR-267670
P51398	Q05655	phosphorylation	up-regulates	0.2	Dap3 is phosphorylated by protein kinase cdelta on thr237. Dap3 was originally identified as a pro-apoptotic protein. The mutation of the phosphorylation site thr237 to alanine reversed the cell death caused by the wild-type dap3	SIGNOR-160488
P35240	Q9UKE5	phosphorylation	up-regulates activity	0.2	Consistently with TNIK modulating Merlin, we also observed reduced YAP levels following TNIK knockdown in LK2 and NCI-H520 cells (Supplementary Fig. S7B).\|Using in vitro kinase assays followed by phosphopeptide mapping, and mass spectrometry analysis on Merlin isolated from cells co-expressing TNIK and Merlin, we determined that TNIK could phosphorylate Merlin at S13, T272, S315, and T576 (Fig. 4B, Supplementary Fig. S4D, and Supplementary Table S3).	SIGNOR-278386
Q8NF50	P17252	phosphorylation	down-regulates activity	0.2	In response to chemokine stimulation, PKC\u03b1 phosphorylates DOCK8 at its three serine sites, promoting DOCK8 separation from LRCH1 and translocation to the leading edge to guide T cell migration.\|Taken our data together, we suggest that PKC\u03b1 phosphorylates DOCK8 at the Ser2077/2082/2087 sites to promote T cell migration.	SIGNOR-279384
P08913	P25098	phosphorylation	down-regulates activity	0.2	The alpha 2A-adrenergic receptor (alpha 2AAR) undergoes rapid functional desensitization caused by phosphorylation of the receptor by the beta-adrenergic receptor kinase (beta ARK). beta ARK-mediated phosphorylation of alpha 2C10 occurs at Ser-296-299 in the third intracellular loop, and this represents the critical step in rapid agonist-promoted desensitization.	SIGNOR-251440
Q9HD90	O00712	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268898
P05556	Q9Y5I3	binding	up-regulates activity	0.2	The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion.	SIGNOR-265663
P67775	Q9UBY8	binding	up-regulates activity	0.2	CLN8 interacts with ceramide binding proteins PP2A and I2PP2A. We showed that the phosphorylation levels of several substrates of PP2A, namely Akt, S6 kinase, and GSK3β, were decreased in CLN8 disease patient fibroblasts. This reduction can be reversed by inhibiting PP2A phosphatase activity with cantharidin, suggesting a higher PP2A activity in CLN8-deficient cells. The phosphorylation levels of PP2A substrates are decreased in the absence of CLN8.	SIGNOR-265583
P16104	P51812	phosphorylation	up-regulates activity	0.2	Herein, we found that ribosomal S6 kinase 2 (RSK2) directly phosphorylates histone H2AX at Ser139 and also at a newly discovered site, Ser16.\|Phosphorylated RSK2 and histone H2AX colocalized in the nucleus following EGF treatment, and the phosphorylation of histone H2AX by RSK2 enhanced the stability of histone H2AX and prevented cell transformation induced by EGF.	SIGNOR-279349
Q9UGM6	Q2TAL8	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269411
P61160	O95390	binding	up-regulates	0.2	Here we demonstrate using genetic and biochemical studies that actriib and its subfamily receptor, actriia, cooperatively mediate the gdf11 signal in patterning the axial vertebrae, and that gdf11 binds to both actriia and actriib, and induces phosphorylation of smad2.	SIGNOR-144147
Q96PE2	P33981	phosphorylation	down-regulates activity	0.2	Because Mps1 also phosphorylates ARHGEF17, the Mps1\u2013ARHGEF17 complex is short lived and promotes its own dissociation, which in turn releases Mps1 and ARHGEF17 from the kinetochore.\|ARHGEF17 and Mps1 interact during mitosis and Mps1 phosphorylates ARHGEF17.	SIGNOR-279352
Q15038	Q9H2X6	phosphorylation	down-regulates activity	0.2	In response to DNA damage, HIPK2 phosphorylates DAZAP2 at several Ser/Thr residues including Ser77, which inhibits its HIPK2-degrading function and targets it to the cell nucleus.	SIGNOR-279335
Q99835	O00141	binding	down-regulates	0.2	SGK1 is known to inhibit another intrinsic pathway, the Hedgehog pathway, through downregulation of SMO and the GLI transcription factor family	SIGNOR-251673

P05114

P68400

0

phosphorylation

down-regulates

0.2

Protein kinases that phosphorylate hmg-14 17 at the major sites have been implicated from previous in vitro studies. Protein kinase c and a similar calcium phospholipid-dependent kinase have been reported to phosphorylate both proteins in vitro, where the phosphorylation of hmg-17 occurs predominantly at ser24 and to a lesser degree at ser28. Phosphorylation of hmg-14 at ser6 by camp- or cgmp-dependent kinases has also been reported. Thus, other kinases may contribute to phosphorylation at ser6 in response to oa. Ser88 and ser98 on hmg-14 are also phosphorylated by casein kinase ii in vitro. we conclude that the correlation we observe reflects a causal relationship, in which phosphorylation somehow facilitates the redistribution of hmg-14 and -17 toward non-nuclear pools.

SIGNOR-76274

Q9H0Z9

P49841

0

phosphorylation

down-regulates

0.2

Here, we showed that rnpc1 is phosphorylated at ser195 by glycogen synthase kinase 3 (gsk3). We also provided evidence that ser195 phosphorylation converts rnpc1 from a repressor to an activator of p53.

SIGNOR-203011

P31995

P07948

0

phosphorylation

up-regulates activity

0.2

Fyn and Blk definitely phosphorylate Y-282 in the ITAM of FcgRIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addition to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation

SIGNOR-262676

P09488

P10242

0

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

P35568

P17612

0

phosphorylation

down-regulates quantity by destabilization

0.2

Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223

SIGNOR-235675

Q96F46

P49840

0

phosphorylation

down-regulates quantity by destabilization

0.2

Glycogen synthase kinase 3 (GSK3) constitutively bound to and phosphorylated IL-17RA at T780, leading to ubiquitination and proteasome-mediated degradation of IL-17RA, thus inhibiting IL-17-mediated inflammation.

SIGNOR-277206

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

P49959

Q9NRR5

0

binding

up-regulates activity

0.2

These data suggest that MRE11 is one of probably many UBQLN4 interaction partners. >Particularly HRR is dependent on ATM activity (Dietlein et al., 2014). Here, we showed that UBQLN4 is an ATM substrate and that DSB sealing is markedly impaired in UBQLN4-depleted cells. HRR depends on a 5′-3′ DSB end resection, which is initiated by the MRE11 nuclease

SIGNOR-265077

P46937

Q01538

0

transcriptional regulation

down-regulates quantity by repression

0.2

Myt1 and Myt1l transcription factors limit proliferation in GBM cells by repressing YAP1 expression. Examination of the gene expression changes in cells expressing Myt1 or Myt1l suggests that both repress expression of the YAP1 transcriptional coactivator, which functions primarily in the Hippo signaling pathway. Expression of YAP1 and its target genes is reduced in Myt-expressing cells, and there is an inverse correlation between YAP1 and MYT1/MYT1L expression in human brain cancer datasets. Together, our data suggest that Myt1 and Myt1l directly repress expression of YAP1, a protein which promotes proliferation and GBM growth.

SIGNOR-266777

O14649

Q13464

0

phosphorylation

down-regulates

0.2

Task1 channels contain two putative rho kinase phosphorylation sites, ser(336) and ser(393) . Mutation of ser(393) rendered task1 channels insensitive to et(a) - or et(b)-mediated current inhibition. In contrast, removal of ser(336) selectively attenuated et(a) -dependent task1 regulation without affecting the et(b) pathway.

SIGNOR-176025

P53539

P59595

0

transcriptional regulation

up-regulates quantity by expression

0.2

The transcription factors c-Fos, FosB, CREB-1, and ATF2 were all activated by the addition of SARS-CoV N protein to the sample well

SIGNOR-260728

P17931

P42684

0

phosphorylation

up-regulates

0.2

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

SIGNOR-163747

A2RUS2

Q8IYT8

0

phosphorylation

up-regulates activity

0.2

ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12.

SIGNOR-264733

P84243

Q9NRC8

0

deacetylation

up-regulates activity

0.2

SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation.|Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression.

SIGNOR-275872

Q96QV6

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.

SIGNOR-265401

Q6FI13

Q86Y13

0

monoubiquitination

up-regulates activity

0.2

2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.

SIGNOR-271755

Q9BU19

Q13131

0

phosphorylation

down-regulates

0.2

Arebp is phosphorylated at ser(470) by ampk. Phosphorylation reduces the dna-binding activity of arebp.

SIGNOR-150590

P20671

Q86Y13

0

monoubiquitination

up-regulates activity

0.2

2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.

SIGNOR-271753

P84103

O15355

0

dephosphorylation

down-regulates activity

0.2

Here, we found that the PPM1G regulated SRSF3, and high levels of PPM1G decreased SRSF3 activity in HCC cells.|PPM1G interacted with SRSF3 and dephosphorylated SRSF3.

SIGNOR-277048

P04062

Q9NR19

0

transcriptional regulation

up-regulates quantity by expression

0.2

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

SIGNOR-276552

P43629

P68400

0

phosphorylation

up-regulates quantity by stabilization

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. It seems that phosphorylation of 3DL1 by CK does not significantly affect receptor inhibitory function or turnover, at least in the assays that we have used so far.

SIGNOR-276077

P09471

P08912

0

binding

up-regulates activity

0.2

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

SIGNOR-257009

P52948

P59634

0

binding

down-regulates activity

0.2

Orf6 of SARS-CoV antagonizes host interferon signaling by perturbing nuclear transport, and the NUP98-RAE1 interaction with Orf6 may perform the same function for SARS-CoV-2.

SIGNOR-260976

Q96T58

Q13153

0

phosphorylation

down-regulates activity

0.2

Pak1 phosphorylation sites in SHARP were mapped to Ser3486 and Thr3568 within the SHARP repression domain.

SIGNOR-278968

Q9Y618

Q9UQM7

0

phosphorylation

down-regulates

0.2

We demonstrated that camkii directly bound and phosphorylated smrt at ser-1407, thereby facilitating smrt translocation from the nucleus to the cytoplasm and proteasome-dependent degradation.

SIGNOR-191773

O43251

O14920

0

phosphorylation

up-regulates activity

0.2

Phosphorylation of RTA by IKKbeta increases RTA transcriptional activity and consequently viral mRNA production.

SIGNOR-279336

P63092

P25103

0

binding

up-regulates activity

0.2

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

SIGNOR-256776

Q8WUI4

O94806

0

phosphorylation

up-regulates activity

0.2

Histone deacetylase (HDAC) 5 and 7, two members of the class II of classical HDAC [62], are in vivo substrates of PKD3 and PKD [63]. In response to a variety of signals, including phorbol esters, T cell receptor engagement, vascular endothelial growth factor and angiotensin stimulation, the activity of HDAC5 and 7 are regulated by a mechanism that involves PKD3 and PKD-mediated phosphorylation of the highly conserved Ser259 and Ser498 residues that are located in N-terminus of class II HDACs [63–67].

SIGNOR-275934

Q96PD2

P00519

0

phosphorylation

up-regulates activity

0.2

SFKs and Abl differentially phosphorylate DCBLD1 and DCBLD2 at distinct tyrosine phosphorylation sites.|We report that Src family kinases and Abl differentially promote the interaction between the CRKL-SH2 domain and DCBLD1 and DCBLD2, and while Src family kinases and Abl each promote DCBLD1 and DCBLD2 binding to the CRKL-SH2 domain, the effect of Abl is more pronounced for DCBLD1. 45999997={Domain=45999998 LikeProtein=1399} 45999998="sh2 domain" 45999999="sh2 domain"}

SIGNOR-280167

P08754

Q9HC97

0

binding

up-regulates activity

0.2

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

SIGNOR-256860

Q00987

Q96GD0

0

dephosphorylation

down-regulates activity

0.2

Considering the roles of NF2 in actin dynamics and Mdm2 regulation - , , , it is noteworthy to elucidate whether interaction of PLPP and CIN with NF2 modulates actin dynamics and Mdm2 degradation in neuronal excitability.|Recently, we have reported that PLPP and CIN dephosphorylates Mdm2 at S166 site in activity dependent manners, which inhibits Mdm2 mediated PSD95 degradation by facilitating Mdm2 ubiquitination 38.

SIGNOR-277151

Q0VAM2

Q8TBJ4

0

binding

up-regulates activity

0.2

Oncogenic effects of imbalanced PRG3 are mediated via PRG3-RasGEF1 interaction and Ras activation. PRG3 interacts with RasGEF1 in vivo.We could further show that PRG3 executes the binding to RasGEF1 predominantly via its C-terminal domain (CT) and in the consequence causes Ras activation.

SIGNOR-261806

O15054

Q99814

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-271586

Q16695

Q92830

0

acetylation

down-regulates activity

0.2

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

SIGNOR-269604

P61587

P17252

0

phosphorylation

down-regulates activity

0.2

PKCalpha dependent Rnd3 phosphorylation downregulates Rnd3 inhibitory activity and leads to increased signaling through the Rho-ROCK pathway.|We further show that PKC\u03b1 directly phosphorylates Rnd3 in an in vitro kinase assay.

SIGNOR-279557

O75385

P17252

0

phosphorylation

down-regulates activity

0.2

ULK1 is phosphorylated by PKCalpha at S423 in vivo and in vitro.|PKC\u03b1 phosphorylation of ULK1 does not change its kinase activity

SIGNOR-279558

P48995

Q05655

0

phosphorylation

up-regulates activity

0.2

Taken together, these results indicate that store depletion induces interactions between TRPC1 and PKC\u03b4 in VSMCs, and that these interactions cause PKC\u03b4\u2010dependent phosphorylation of TRPC1.

SIGNOR-279559

P12755

O14965

0

phosphorylation

down-regulates quantity by destabilization

0.2

Here we show that AURKA phosphorylates in vitro the transcripcional co-repressor Ski on aminoacids Ser326 and Ser383. Phosphorylations on these aminoacids decreased Ski protein half-life

SIGNOR-276917

P07766

Q9UJZ1

0

binding

up-regulates activity

0.2

We observed that SLP-2 steadily associated with the CD3-epsilon chain of the TCR complex under resting conditions and during the 60 min of stimulation|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-260375

Q8IVS8

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.2

Mechanistically, glucose deprivation-activated ERK1 phosphorylates GLYCTK2 at serine 220 directly, which prevents STUB1 (ubiquitin E3 ligase) binding, thereby abrogating the ubiquitination and degradation of GLYCTK2. ERK1 phosphorylates GLYCTK2 at S220 to promotes its stability

SIGNOR-280258

P17252

Q13043

0

phosphorylation

up-regulates activity

0.2

Mst1 and Mst2 activate PKC\u03b1 to disrupt the LyGDI-Rac complex.|Thus, the phosphorylation of PKC\u03b1 at Ser226 and Thr228 by Mst1 and Mst2 is required for the optimal activation of PKC\u03b1.

SIGNOR-280146

Q9UMX1

Q8TBB1

0

ubiquitination

down-regulates quantity

0.2

Indeed, they target different lysine residues in the SuFu protein, as LNX1 ubiquitinates SuFu at K59 and K470, and SCF Fbxl17 acts at K257, while Itch ubiquitinates at K321 and K457.|XREF_FIG, ectopic LNX1 expression reduced SuFu protein levels in HEK-293T cells, while shRNA mediated knockdown of LNX1 increased these levels.

SIGNOR-278626

Q8N884

P51451

0

phosphorylation

down-regulates activity

0.2

DNA damage induces nuclear translocation of cGAS in a manner that is dependent on importin-α, and the phosphorylation of cGAS at tyrosine 215-mediated by B-lymphoid tyrosine kinase-facilitates the cytosolic retention of cGAS.

SIGNOR-275844

Q9Y5G1

Q9Y5I2

0

binding

up-regulates activity

0.2

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

SIGNOR-265707

P35236

P24723

0

phosphorylation

up-regulates activity

0.2

HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.

SIGNOR-276049

P07711

Q9UNZ2

0

binding

down-regulates activity

0.2

The SEP domain of p47 acts as a reversible competitive inhibitor of cathepsin L.

SIGNOR-265043

P19532

Q00534

0

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 .|CDK4 and CDK6 phosphorylate TFEB and TFE3.

SIGNOR-279517

Q04206

Q9P286

0

phosphorylation

up-regulates activity

0.2

PAK5-mediated phosphorylation and nuclear translocation of NF-κB-p65 promotes breast cancer cell proliferation in vitro and in vivo|We characterized that PAK5 could promote the phosphorylation and the nuclear translocation of p65 subunit of nuclear factor-kappaB, and demonstrated that p65 could directly bind to the promoter of Cyclin D1

SIGNOR-275657

Q9BYB0

P28482

0

phosphorylation

down-regulates activity

0.2

Interestingly, we discovered that several kinases in the MEK and ERK2 pathway destabilize Shank3 and that genetic deletion and pharmacological inhibition of ERK2 increases Shank3 abundance in vivo.|We also determined that phosphorylation of Shank3 by ERK2 at selective residues promotes its ubiquitination and degradation.

SIGNOR-279538

Q12791

P17252

0

phosphorylation

up-regulates

0.2

Results showed that mutating s1076 altered the effect of pkc activation on bk(ca) channels in hek-293 cells

SIGNOR-186755

Q13470

Q7KZI7

0

phosphorylation

down-regulates activity

0.2

We also discover a MARK-mediated phosphorylation on TNK1 at S502 that promotes an interaction between TNK1 and 14-3-3, which sequesters TNK1 and inhibits its kinase activity.Phosphorylation of TNK1 at S502 within the proline rich domain is required for TNK1 binding to 14-3-3.MARKs mediate phosphorylation at S502 and 14-3-3 binding to TNK1, which restrains the movement of TNK1 into heavy membrane-associated clusters.

SIGNOR-273867

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

P10588

Q05655

0

phosphorylation

down-regulates

0.2

Ser-83 on recombinant nr2f6is a pkc substrate site;mutation of ser-83 (but not ser-89) to alanine strongly reduced pkc-mediated nr2f6 phosphorylation, confirming ser-83 as the major pkc phosphorylation site in nr2f6;the dna-binding capacity of nr2f6 is antagonized by a (p)ser-83 switch on nr2f6.

SIGNOR-180017

Q9NWD9

P53350

0

phosphorylation

up-regulates activity

0.2

In addition, the inhibition of PLK1 activity by BI2536 treatment sharply reduced BEX4 protein, which was localized at the centrosomes in the HeLa cells or the GFP-BEX4 stable cell lines.|PLK1 directly phosphorylates BEX4 at T107 and contributes to BEX4-induced aneuploidy.

SIGNOR-279550

P35916

O43915

0

binding

up-regulates

0.2

Vegf-d is a ligand for both vegf receptors (vegfrs) vegfr-2 (flk1) and vegfr-3 (flt4) and can activate these receptors.

SIGNOR-55065

Q15054

P17612

0

phosphorylation

down-regulates

0.2

In this study, we identified s458, located in the pcna-interacting protein (pip-box) motif of p68, as a phosphorylation site for pka. Phosphomimetic mutation of s458 resulted in a decrease in p68 affinity for pcna as well as the processivity of pol _.

SIGNOR-195203

P19532

P11802

0

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

Q04760

P12931

0

phosphorylation

up-regulates activity

0.2

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

SIGNOR-276189

Q587J8

Q13315

0

phosphorylation

up-regulates activity

0.2

Notably, we identified two critical residues, Thr145 and Thr156, whose phosphorylation by Ataxia-telangiectasia mutated (ATM) is essential for KHDC3L's functions.

SIGNOR-273505

Q7Z2W7

P17612

0

phosphorylation

up-regulates activity

0.2

Using specific pharmacological and molecular tools combined with patch-clamp current recordings, we found that in heterologously expressed HEK-293 (human embryonic kidney) cells, TRPM8 channel is inhibited by the G(i) protein/adenylate cyclase (AC)/cAMP/protein kinase A (PKA) signaling cascade. We further identified the TRPM8 S9 and T17 as two key PKA phosphorylation sites regulating TRPM8 channel activity. the intracellular serine/threonine protein phosphatase 2A (PP2A) dephosphorylates TRPM8 Ser-9 and Thr-17 inhibiting the channel activity.

SIGNOR-273791

P38405

Q99500

0

binding

up-regulates activity

0.2

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

SIGNOR-256933

P63092

P55085

0

binding

up-regulates activity

0.2

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

SIGNOR-256752

P19086

Q15391

0

binding

up-regulates activity

0.2

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

SIGNOR-257118

P17096

Q13315

0

phosphorylation

up-regulates activity

0.2

21 As shown in Fig. 2 b, ATM was able to phosphorylate in vitro the C-terminal peptide of HMGA1.

SIGNOR-279493

P27707

Q13535

0

phosphorylation

up-regulates activity

0.2

Since activation of dCK by IR was not prevented by KU-60019 at longer times, but could be suppressed if the ATR inhibitor was combined with the ATM inhibitor, we propose that dCK is activated by ATR when ATM is inhibited.|Taken together, these data indicate that ATR, like ATM [15], can directly phosphorylate dCK at Ser 74 in vitro and thereby increase its activity.Most dCK activators share the feature of inducing DNA damage followed by DNA damage response, a complex signaling network aimed to preserve genome integrity.

SIGNOR-279494

P02671

P50281

0

cleavage

down-regulates quantity by destabilization

0.2

Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.|MMP-14 27YVATRDN g-chain| 105XDAATLKSR g-chain | 92LTYNPDES g-chain |105LTTNIXEXL a-chain|433LVTSKGDKE a-chain| 117FXSANNRD a-chain

SIGNOR-263620

Q86WV6

Q9C029

0

ubiquitination

down-regulates quantity by destabilization

0.2

RNF90 promoted K48-linked ubiquitination of MITA and its proteasome-dependent degradation.|Finally, in vitro ubiquitination assays suggested that RNF90 promoted the ubiquitination of MITA directly (Fig 5E and 5F).

SIGNOR-278678

Q96A54

P25098

0

phosphorylation

down-regulates activity

0.2

AdipoR1 is Directly Phosphorylated by GRK2.|In summary, our study demonstrates for the first time that cardiometabolic-regulatory, anti-inflammatory, and cardioprotective functions of APN are significantly impaired by GRK2 mediated AdipoR1 phosphorylative desensitization during a critical period of post-MI HF development.

SIGNOR-279463

P68431

Q9NRC8

0

deacetylation

up-regulates activity

0.2

SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation.|Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression.

SIGNOR-275874

P38398

Q00341

0

binding

up-regulates activity

0.2

We show that vigilin interacts with the DNA damage response (DDR) proteins RAD51 and BRCA1, and vigilin depletion impairs their recruitment to DSB sites.

SIGNOR-266698

Q969R2

P48729

0

phosphorylation

up-regulates activity

0.2

CK1a1, JNK1 and CDK1 had the highest site-specific activity for ORP4L, while CDK1, GSK3a, CK1a1 and GSK3b showed the highest specificity for the site when corrected for background activity with ORP4L-S4A. Because of the complexity of the serine/proline-rich site, we did not determine which serine(s) in ORP4L were phosphorylated by candidate kinases.|We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes.

SIGNOR-264877

P05230

Q05655

0

phosphorylation

up-regulates quantity

0.2

Translocated FGF1 can be phosphorylated by PKC\u03b4 on serine 130.

SIGNOR-278451

Q9Y4G8

P48729

0

phosphorylation

down-regulates quantity by destabilization

0.2

Here, we report that in response to factors that promote cell motility, the Rap guanine exchange factor RAPGEF2 is rapidly phosphorylated by I-kappa-B-kinase-β and casein kinase-1α and consequently degraded by the proteasome via the SCF(βTrCP) ubiquitin ligase.

SIGNOR-276604

Q9H2S1

P17612

0

phosphorylation

down-regulates

0.2

Mutagenesis and mass spectrometry studies identified four pka phosphorylation sites: ser465 (minor site) and three amino acid residues ser568, ser569, and ser570 (major sites) within the carboxyl-terminal region. pka activation decreased sk2 surface localization

SIGNOR-145040

O95379

P63096

0

binding

up-regulates activity

0.2

TNFAIP8: a new effector for Galpha(i) coupling to reduce cell death and induce cell transformation

SIGNOR-256491

P35236

Q02156

0

phosphorylation

up-regulates activity

0.2

HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.

SIGNOR-276050

P07355

P07947

0

phosphorylation

up-regulates activity

0.2

Activated YES1 interacts with ANXA2 andphosphorylates ANXA2 at Tyr24 site that induces ANXA2 activation and increases ANXA2 nuclear distribution , leading to activation of the tumorpromoting transcription factors ( such as Myc , Stat3 , Stat6 ) that promotes GC invasion and metastasis .|YES1 phosphorylates ANXA2 at Tyr24 site that leads to ANXA2 activation and increased ANXA2 nuclear distribution.

SIGNOR-279435

Q15121

Q9UQM7

0

phosphorylation

up-regulates

0.2

Pea-15 is a phosphoprotein containing a ser-104 phosphorylated by protein kinase c and a ser-116 phosphorylated by camkii (calcium/calmodulin-dependent protein kinase ii) or akt. Phosphorylation of ser-104 is implicated in the regulation of glucose metabolism, while phosphorylation at ser-116 is required for pea-15 recruitment to the disc (death-initiation signalling complex)

SIGNOR-137614

Q8WUX9

P06493

0

phosphorylation

down-regulates activity

0.2

We found that recombinant CHMP7 could be directly phosphorylated by CDK1/CCNB1 in vitro and that CDK1-phosphorylation reduced the capacity of CHMP7 to sediment (Figure 4A and B).|We identified direct CDK1 phosphorylation of CHMP7 at Ser3 and Ser441 as a suppressor of both CHMP7\u2019s ability to interact with LEM2 and its ability to assemble, as judged by sedimentation assays.

SIGNOR-279445

Q9UKT5

P49841

0

phosphorylation

up-regulates

0.2

Gsk3beta-mediated phosphorylation of fbx4 ser12 during the g1/s transition regulates fbx4 dimerization, which in turn governs fbx4-driven e3 ligase activity.

SIGNOR-171648

Q13200

Q9P1W9

0

phosphorylation

up-regulates activity

0.2

Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B).

SIGNOR-273896

P51608

O15111

0

phosphorylation

up-regulates activity

0.2

Representative confocal micrographs of 4th day differentiating cultures are shown. (C) IKK\u03b1 promotes MeCP2-dependent BDNF expression.|The characterization of IKK\u03b1-mediated phosphorylation of MeCP2 at Ser421 and other residues and their effects on the activity of MeCP2 is a topic of current work in our laboratory.

SIGNOR-279459

P63215

Q99835

0

binding

up-regulates

0.2

Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling.

SIGNOR-148598

O75420

Q92600

0

binding

up-regulates activity

0.2

Through interaction analysis of RQCD1 with full-length or partial proteins of GIGYF1 and GIGYF2, segments corresponding to 620-665th and 667-712th amino acids were identified as potential interacting regions on GIGYF1 and GIGYF2, respectively, with RQCD1. we found that RQCD1 was required for enhancement of the interaction of Grb10 with GIGYF1 and GIGYF2

SIGNOR-260059

Q93096

P30291

0

phosphorylation

down-regulates activity

0.2

In this study , we found that WEE1 phosphorylates PRL1 and promotes PRL1 degradation .|In this study, we demonstrated that WEE1 phosphorylates and inhibits PRL1 to regulate alternative splicing of CYCD1;1 and CYCD3;1 , which may represent a new cell cycle control mechanism.

SIGNOR-278434

Q8NER1

Q00535

0

phosphorylation

up-regulates activity

0.2

TNF-alpha overexpression increased Cdk5-mediated phosphorylation of TRPV1 at T407.|These results suggest that the activation of Cdk5 by p35 enhances the response of TRPV1 to capsaicin, probably by phosphorylation of the channel [34].

SIGNOR-278437

O43236

O15033

0

ubiquitination

down-regulates quantity by destabilization

0.2

Furthermore, the ubiquitination and degradation of SMAC, HtrA2, and ARTS were significantly enhanced in AREL1-expressing cells following apoptotic stimulation, indicating that AREL1 binds to and ubiquitinates cytosolic but not mitochondria-associated forms of IAP antagonists

SIGNOR-267670

P51398

Q05655

0

phosphorylation

up-regulates

0.2

Dap3 is phosphorylated by protein kinase cdelta on thr237. Dap3 was originally identified as a pro-apoptotic protein. The mutation of the phosphorylation site thr237 to alanine reversed the cell death caused by the wild-type dap3

SIGNOR-160488

P35240

Q9UKE5

0

phosphorylation

up-regulates activity

0.2

Consistently with TNIK modulating Merlin, we also observed reduced YAP levels following TNIK knockdown in LK2 and NCI-H520 cells (Supplementary Fig. S7B).|Using in vitro kinase assays followed by phosphopeptide mapping, and mass spectrometry analysis on Merlin isolated from cells co-expressing TNIK and Merlin, we determined that TNIK could phosphorylate Merlin at S13, T272, S315, and T576 (Fig. 4B, Supplementary Fig. S4D, and Supplementary Table S3).

SIGNOR-278386

Q8NF50

P17252

0

phosphorylation

down-regulates activity

0.2

In response to chemokine stimulation, PKC\u03b1 phosphorylates DOCK8 at its three serine sites, promoting DOCK8 separation from LRCH1 and translocation to the leading edge to guide T cell migration.|Taken our data together, we suggest that PKC\u03b1 phosphorylates DOCK8 at the Ser2077/2082/2087 sites to promote T cell migration.

SIGNOR-279384

P08913

P25098

0

phosphorylation

down-regulates activity

0.2

The alpha 2A-adrenergic receptor (alpha 2AAR) undergoes rapid functional desensitization caused by phosphorylation of the receptor by the beta-adrenergic receptor kinase (beta ARK). beta ARK-mediated phosphorylation of alpha 2C10 occurs at Ser-296-299 in the third intracellular loop, and this represents the critical step in rapid agonist-promoted desensitization.

SIGNOR-251440

Q9HD90

O00712

0

transcriptional regulation

up-regulates quantity

0.2

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

SIGNOR-268898

P05556

Q9Y5I3

0

binding

up-regulates activity

0.2

The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion.

SIGNOR-265663

P67775

Q9UBY8

0

binding

up-regulates activity

0.2

CLN8 interacts with ceramide binding proteins PP2A and I2PP2A. We showed that the phosphorylation levels of several substrates of PP2A, namely Akt, S6 kinase, and GSK3β, were decreased in CLN8 disease patient fibroblasts. This reduction can be reversed by inhibiting PP2A phosphatase activity with cantharidin, suggesting a higher PP2A activity in CLN8-deficient cells. The phosphorylation levels of PP2A substrates are decreased in the absence of CLN8.

SIGNOR-265583

P16104

P51812

0

phosphorylation

up-regulates activity

0.2

Herein, we found that ribosomal S6 kinase 2 (RSK2) directly phosphorylates histone H2AX at Ser139 and also at a newly discovered site, Ser16.|Phosphorylated RSK2 and histone H2AX colocalized in the nucleus following EGF treatment, and the phosphorylation of histone H2AX by RSK2 enhanced the stability of histone H2AX and prevented cell transformation induced by EGF.

SIGNOR-279349

Q9UGM6

Q2TAL8

0

transcriptional regulation

up-regulates quantity by expression

0.2

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269411

P61160

O95390

0

binding

up-regulates

0.2

Here we demonstrate using genetic and biochemical studies that actriib and its subfamily receptor, actriia, cooperatively mediate the gdf11 signal in patterning the axial vertebrae, and that gdf11 binds to both actriia and actriib, and induces phosphorylation of smad2.

SIGNOR-144147

Q96PE2

P33981

0

phosphorylation

down-regulates activity

0.2

Because Mps1 also phosphorylates ARHGEF17, the Mps1\u2013ARHGEF17 complex is short lived and promotes its own dissociation, which in turn releases Mps1 and ARHGEF17 from the kinetochore.|ARHGEF17 and Mps1 interact during mitosis and Mps1 phosphorylates ARHGEF17.

SIGNOR-279352

Q15038

Q9H2X6

0

phosphorylation

down-regulates activity

0.2

In response to DNA damage, HIPK2 phosphorylates DAZAP2 at several Ser/Thr residues including Ser77, which inhibits its HIPK2-degrading function and targets it to the cell nucleus.

SIGNOR-279335

Q99835

O00141

0

binding

down-regulates

0.2

SGK1 is known to inhibit another intrinsic pathway, the Hedgehog pathway, through downregulation of SMO and the GLI transcription factor family

SIGNOR-251673