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
O75461	O14757	0	phosphorylation	down-regulates activity	0.574	the checkpoint kinase Chk1 phosphorylates E2F6 leading to its dissociation from promoters.	SIGNOR-266371
P41279	Q02750	1	phosphorylation	up-regulates	0.574	Activation of mek family kinases requires phosphorylation of two conserved ser/thr residues.Phosphopeptide analysis demonstrated that serine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf	SIGNOR-36453
P20749	O15379	2	binding	up-regulates	0.348	We show that bcl-3 is a substrate for the protein kinase gsk3 and that gsk3-mediated bcl-3 phosphorylation, which is inhibited by akt activation, targets its degradation through the proteasome pathway. This phosphorylation modulates its association with hdac1, 3 and 6.	SIGNOR-129804
P06493	P55211	1	phosphorylation	down-regulates	0.429	Here, we show that the apoptotic initiator protease caspase-9 is regulated during the cell cycle through periodic phosphorylation at an inhibitory site, thr125. This site is phosphorylated by cdk1/cyclin b1 during mitosis and in response to microtubule poisons that arrest cells at this stage of the cell cycle.	SIGNOR-141621
P53350	O00139	1	phosphorylation	up-regulates activity	0.684	Taken together, KIF2A is phosphorylated at T554 by PLK1 in the subdistal appendages of the mother centriole, which enhances MT depolymerization to disassemble primary cilia in a growth-signal-dependent manner.\|Thus, PLK1 and APC/C mediated dual regulation connect the MT depolymerizing activity of KIF2A to a physiological primary cilia disassembly during the proliferative phase.	SIGNOR-278380
O00327	P49841	0	phosphorylation	down-regulates	0.382	Gsk3beta phosphorylates bmal1 specifically on ser 17 and thr 21 and primes it for ubiquitylation. In the absence of gsk3beta-mediated phosphorylation, bmal1 becomes stabilized and bmal1 dependent circadian gene expression is dampened.	SIGNOR-162786
Q14934	Q9Y625	1	transcriptional regulation	up-regulates quantity by expression	0.2	NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype.	SIGNOR-264023
Q8N6U8	O75386	0	relocalization	up-regulates activity	0.608	Upon knockdown of Tulp3 using siRNA in IMCD3 cells, ciliary localization of Gpr161 was severely reduced	SIGNOR-259938
Q6PIY7	P22694	0	phosphorylation	down-regulates activity	0.2	We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition.	SIGNOR-259403
O43293	O14950	1	phosphorylation	up-regulates	0.511	Hzipk phosphorylated the regulatory light chain of myosin ii (mrlc) at both ser19 and thr18 in vitro. Phosphorylation of mrlc is required to generate the driving force in the migration of the cells but not necessary for localization of myosin ii at the leading edge.	SIGNOR-16043
P35222	P15884	2	binding	up-regulates activity	0.69	beta-catenin interacts with the TCF/Lef family transcription factors.	SIGNOR-178042
Q13261	P40933	2	binding	up-regulates	0.868	Interleukin-15 specificity and high affinity binding are conferred by the IL-5-specific but nonsignaling IL-15R alpha subunit, which is structurally similar (but not homologous) to the alpha receptor subunit of IL-2	SIGNOR-157415
Q9HBY8	O15530	0	phosphorylation	up-regulates activity	0.596	SGK2 and SGK3 are activated in vitro by PDK1, albeit more slowly than SGK1, and their activation is accompanied by the phosphorylation of Thr(193) and Thr(253) respectively. The PDK1-catalysed phosphorylation and activation of SGK2 and SGK3, like SGK1, is greatly potentiated by mutating Ser(356) and Ser(419) respectively to Asp, these residues being equivalent to the C-terminal phosphorylation site of PKB.	SIGNOR-250277
P49841	P22415	1	phosphorylation	up-regulates activity	0.286	Both MITF and USF1 were activated by glycogen synthase kinase (GSK) 3, with GSK3 phosphorylation sites on USF1 identified as the previously described activating site threonine 153 as well as serine 186.	SIGNOR-276355
P68400	P78344	1	phosphorylation	up-regulates activity	0.226	DAP5(S902) is phosphorylated by CK2α. Phosphorylation of DAP5(S902) by CK2α is required for eIF2β binding.	SIGNOR-266384
Q16254	O15392	1	transcriptional regulation	down-regulates quantity by repression	0.334	This TGF-beta response is triggered through a Smad2/3-dependent hypophosphorylation of Rb and the subsequent association of the Rb/E2F4 repressive complex to CDE/CHR elements in the proximal region of the survivin promoter.	SIGNOR-271678
Q6DKK2	Q9H1H9	2	binding	up-regulates activity	0.432	We show that PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26), and its binding partner TTC19, which in turn interacts with CHMP4B, an endosomal sorting complex required for transport (ESCRT)-III subunit implicated in the abscission step of cytokinesis. On the basis of these data and the high-content microscopy described above, we propose that PtdIns(3)P controls the KIF13A-dependent recruitment of FYVE-CENT and TTC19 to the midbody, and that TTC19 is the most downstream effector of the three, possibly controlling the function of CHMP4B.	SIGNOR-265540
Q13153	O95863	1	phosphorylation	up-regulates	0.4	Pak1 regulates the repressor activity of snail by phosphorylating on ser(246). Pak1 phosphorylation of snail supports snail's accumulation in the nucleus as well as its repressor functions.	SIGNOR-135605
Q9UNH5	P30305	1	dephosphorylation	down-regulates activity	0.56	Cdc14A inhibits Cdc25A and Cdc25B activity, the latter through direct binding and dephosphorylation ( ).\|Together, these data indicate that Cdc14A dephosphorylates Cdc25B, inhibiting its catalytic activity.	SIGNOR-276968
Q6ZUM4	P63000	1	gtpase-activating protein	down-regulates activity	0.589	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-260482
P11802	P30304	0	dephosphorylation	up-regulates activity	0.705	Invalidation of CDK4 has no impact by itself on the cell proliferation, but invalidation of CDC25A prevents the dephosphorylation of CDK6 (Y24) and CDK4 (Y17) residues, and impedes their association with CCNDs.	SIGNOR-267568
Q13315	Q15911	1	phosphorylation	up-regulates activity	0.346	Indeed, ATM phosphorylates ATBF1 at Ser1180 in HEK293T cells exposed to 10-Gy radiation [ xref ].\|We also found in this study that ATBF1 mediated neuronal death is dependent on ATM signals because the blockage of ATM by treatment with ATM inhibitors, caffeine and KU55933, abolished ATBF1 functions in neuronal death.	SIGNOR-279138
Q05639	P15056	0	phosphorylation	down-regulates quantity by destabilization	0.326	Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B- and C-Raf.	SIGNOR-276406
Q96B36	P31749	0	phosphorylation	down-regulates activity	0.782	Treatment of these cells with 4-hydroxytamoxifen stimulated the phosphorylation of wt PRAS40 but not the mutant PRAS40 in which Thr-246 was mutated. These results demonstrate that activation of Akt alone is sufficient to induce phosphorylation of PRAS40	SIGNOR-252544
P07948	Q96P20	1	phosphorylation	down-regulates	0.29	Lyn phosphorylates NLRP3 at Tyr 918 and controls NLRP3 ubiquitination.\|Therefore, our data collectively indicate that Lyn inhibits the NLRP3 inflammasome in vivo.	SIGNOR-278485
Q96S53	P23528	1	phosphorylation	down-regulates activity	0.503	Like tesk1, tesk2 phosphorylated cofilin specifically at ser-3 and induced formation of actin stress fibers and focal adhesions.	SIGNOR-108753
P04637	O15111	0	phosphorylation	up-regulates activity	0.429	In the nucleus, IKKalpha enhances p53 mediated GADD45 and BAD gene expressions by phosphorylating p53 at Ser20 and stabilizing p53 protein levels , leading to the induction of apoptosis in response to ROS exposure.\|PKC-activated nuclear I\u03baB kinase\u03b1 promotes the stability of p53 protein and mediates reactive oxygen species-induced apoptosis [ ].	SIGNOR-280231
P55957	P68400	0	phosphorylation	up-regulates activity	0.286	Here we report that Bid is phosphorylated by casein kinase I (CKI) and casein kinase II (CKII). Inhibition of CKI and CKII accelerated Fas-mediated apoptosis and Bid cleavage, whereas hyperactivity of the kinases delayed apoptosis. \| These results suggest that residues S61, S64, and to a much lesser extent T58 are sites of phosphorylation of Bid.	SIGNOR-250831
P49840	P31751	0	phosphorylation	down-regulates	0.557	Activated pi3k/akt pathway results in inhibitory phosphorylation of gsk3	SIGNOR-138179
P06493	P51003	1	phosphorylation	up-regulates activity	0.258	Once an oocyte resumes meiosis, activated CDK1 and ERK1/2 cooperatively mediate the phosphorylation of three serine residues of PAPalpha, 537, 545 and 558, thereby leading to increased activity.	SIGNOR-268338
P46695	Q13362	2	binding	down-regulates	0.542	Iex-1 binds to b56 subunits and perk independently, enhances b56 phosphorylation by erk at a conserved ser/pro site in this complex and triggers dissociation from the catalytic subunit.	SIGNOR-144309
Q4V328	P42574	0	cleavage	up-regulates activity	0.414	These results suggest that the region of GRASP‐1 downstream of the Caspase‐3‐cleavage site is capable of activating the JNK signaling pathway by enhancing the phosphorylation of JNK. these results suggest that full length GRASP‐1 does not enhance JNK pathway activity, possibly due to the inhibitory effect of the N‐terminal fragment on the C‐terminal fragment. In contrast, Caspase‐3 cleavage of GRASP‐1 releases the C‐terminal fragment, which in turn activates JNK signaling by serving as a scaffold protein.	SIGNOR-260641
Q96DT5	Q96M91	2	binding	up-regulates activity	0.2	CFAP53 likely facilitates the transport of TTC25 and the dyneins into cilia. CFAP53 at the centriolar satellites may form a complex with TTC25 and ODAs, including DNAH5 and DNAH11, and regulate their trafficking into the cilium (Fig 10B).	SIGNOR-265545
Q86UX7	P05106	2	binding	up-regulates activity	0.65	Mechanistically, Kindlin-3 can directly bind to regions of beta-integrin tails distinct from those of Talin and trigger integrin activation. We have therefore identified Kindlin-3 as a novel and essential element for platelet integrin activation in hemostasis and thrombosis\|Kindlin-3 was also able to interact with the wild-type beta1 and beta3 integrin tails (Fig. 3c), in the presence and absence of Talin1 (Supplementary Fig. 3 online), and the F3 subdomain of Kindlin-3 was sufficient for this interaction and this interaction occurred in a direct manner	SIGNOR-266066
P48169	Q8TAB3	2	binding	up-regulates quantity by stabilization	0.2	Here, we found that PCDH19 binds the alpha subunits of GABAAR and regulates its surface availability and currents in cultured hippocampal neurons. The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated. Here, we identified a new interaction between PCDH19 and GABAA receptor (GABAAR) alpha subunits in the rat brain. PCDH19 shRNA-mediated downregulation reduces GABAAR surface expression and affects the frequency and kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in cultured hippocampal neurons.	SIGNOR-267220
Q86U70	Q9NVW2	0	polyubiquitination	down-regulates quantity by destabilization	0.566	Here we identify RLIM as a ubiquitin protein ligase that is able to target CLIM cofactors for degradation through the 26S proteasome pathway.	SIGNOR-272617
P25116	O95837	2	binding	up-regulates activity	0.439	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-257293
Q16665	Q96KS0	0	hydroxylation	down-regulates quantity by destabilization	0.856	There are three EglN family members in humans and mice (EglN1, EglN2, and EglN3). Their enzymatic activity requires oxygen, ascorbic acid, iron, and α-ketoglutarate (α-KG). Under hypoxic conditions, EglNs lose their activity and fail to hydroxylate HIFα, which leads to HIFα stabilization	SIGNOR-261999
Q9P2P5	O15350	1	ubiquitination	up-regulates quantity by stabilization	0.37	P73 was efficiently ubiquitinated but stabilized in a NEDL2-dependent manner. Accordingly, p73 decayed at faster rates in the absence of NEDL2 than in its presence. Consistent with the NEDL2-mediated stabilization of p73, NEDL2 enhanced the p73-dependent transcriptional activation. Thus, our results suggest that NEDL2 activates the function of p73 by increasing its stability.	SIGNOR-269457
P11309	Q96T88	1	phosphorylation	down-regulates quantity by destabilization	0.2	Here we report that UHRF1 is a novel substrate of PIM1 kinase, which could be phosphorylated at Ser311 and therefore promoted to degradation.	SIGNOR-277349
P27361	Q07820	1	phosphorylation	up-regulates	0.436	We then showed that erk could phosphorylate mcl-1 at two consensus residues, thr 92 and 163, which is required for the association of mcl-1 and pin1, resulting in stabilization of mcl-1.	SIGNOR-179812
P06493	P08670	1	phosphorylation	down-regulates	0.362	These results strongly suggest that cdc2 kinase is the kinase which phosphorylates vimentin ser55 in the entire cytoplasm during mitosis and that the appearance of immunoreactivities with antibody 4a4 in cell staining indeed reflect the vimentin phosphorylation by cdc2 kinase. immunofluorescent evidence using antibody 4a4 and biochemical analysis using vimentin ser55 peptide showed that the degree of disassembly of vimentin filament of various cell types at early mitotic phase correlated well with the amount of mitotically activated cdc2 kinase.	SIGNOR-35492
P19086	P55085	2	binding	up-regulates activity	0.334	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-257232
P23443	O00418	1	phosphorylation	down-regulates activity	0.736	We show that two such kinases, p70 s6 kinase (regulated via mtor) and p90(rsk1) (activated by erk), phosphorylate eef2k at a conserved serine and inhibit its activity	SIGNOR-109712
O00308	P11161	1	ubiquitination	down-regulates quantity	0.372	The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-induced T-cell death by catalyzing EGR2 ubiquitination\|AIP2 interacts with and promotes ubiquitin-mediated degradation of EGR2, a zinc finger transcription factor that has been found to regulate Fas ligand (FasL) expression during activation-induced T-cell death.	SIGNOR-268849
P01106	P17480	1	transcriptional regulation	up-regulates quantity by expression	0.356	MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation\|MAD1 repressed and c-MYC activated rDNA transcription in nuclear run-on assays. Repression of rDNA transcription by MAD1 was associated with its ability to interact directly with the promoter of upstream binding factor (UBF), an rDNA regulatory factor. Conversely, c-MYC activated transcription from the UBF promoter.	SIGNOR-269644
Q14344	O43614	2	binding	up-regulates activity	0.25	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257350
Q13470	Q96L34	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-273865
P68400	Q92598	1	phosphorylation	down-regulates activity	0.329	Protein kinase CK2 phosphorylates Hsp105 alpha at Ser509 and modulates its function. \| the phosphorylation of Hsp105 alpha at Ser(509) abolished the inhibitory activity of Hsp105 alpha in vitro.	SIGNOR-250901
O00631	O14983	2	binding	down-regulates activity	0.55	These results suggest that sAnk1 interacts with SLN both directly and in complex with SERCA1 and reduces SLN's inhibitory effect on SERCA1 activity.	SIGNOR-265929
P06493	Q9Y2I6	1	phosphorylation	down-regulates quantity by destabilization	0.422	In this study, we show that Nlp can be phosphorylated by cell cycle protein kinase Cdc2/cyclin B1. The phosphorylation sites of Nlp are mapped at Ser185 and Ser589. the phosphorylation at the site Ser589 by Cdc2/cyclin B1 plays an important role in Nlp protein stability probably due to its effect on protein degradation.	SIGNOR-259831
P31749	Q16584	1	phosphorylation	down-regulates	0.4	Negative regulation of mixed lineage kinase 3 by protein kinase b/akt leads to cell survivalthe expression of activated akt1 inhibits mlk3-mediated cell death in a manner dependent on serine 674 phosphorylation.	SIGNOR-252592
O15355	P84103	1	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
P09471	P25101	2	binding	up-regulates activity	0.272	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-257253
Q12923	P06213	1	dephosphorylation	down-regulates	0.26	We demonstrate that ptpl1, like ptp1b, interacts with and dephosphorylates a bis-phosphorylated insulin receptor peptide more efficiently than monophosphorylated peptides, indicating that ptpl1 may down-regulate the phosphatidylinositol 3-kinase pathway, by dephosphorylating insulin or growth factor receptors that contain tandem phosphotyrosines.	SIGNOR-132555
P06730	Q9UDX5	1	translation regulation	up-regulates activity	0.2	In this study, we demonstrate that mTORC1 stimulates mitochondrial fission via 4E-BP-mediated translational regulation of the mitochondrial fission factor MTFP1. Suppression of mTORC1 activity by pharmacological or genetic means causes mitochondrial hyperfusion, branching, and circularization. This is a consequence of downregulation of MTFP1 levels via the mTORC1/4E-BP pathway, thereby eliciting changes in phosphorylation and localization of the mitochondrial fission factor DRP1	SIGNOR-275429
Q9UBE8	P46937	1	phosphorylation	up-regulates activity	0.2	Here, we report that osmotic stress stimulates transient YAP nuclear localization and increases YAP activity even when YAP Ser127 is phosphorylated. Osmotic stress acts via the NLK kinase to induce YAP Ser128 phosphorylation. Phosphorylation of YAP at Ser128 interferes with its ability to bind to 14-3-3, resulting in YAP nuclear accumulation and induction of downstream target gene expression.	SIGNOR-273909
Q8IU57	P23458	2	binding	up-regulates	0.78	Each r1-type chain (il-10r1, il-20r1, il-22r1, ifn-_r1 and ifn-_r1) is associated with jak1 tyrosine kinase and mediates recruitment of a variety of signaling molecules after being phosphorylated on its intracellular domain.	SIGNOR-124480
O00470	P28358	2	binding	up-regulates activity	0.375	We now show that the Hoxa-9 protein physically interacts with Meis1 proteins. Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.	SIGNOR-241226
Q8IZP0	P28482	0	phosphorylation	up-regulates	0.445	Our mass spectrometry also identified abi1 s183 and s225 on abi1 (numbering corresponds to abi1 isoform 1) as sites phosphorylated on endogenous protein and in the wildtype erk-dependent in vitro phosphorylated sample. these data indicate erk phosphorylation of abi1 is required for basal and egf-induced wrc interaction with the wrp2/3 complex.	SIGNOR-172873
P02533	Q15628	2	binding	down-regulates activity	0.346	TRADD specifically bound K18 and K14, type I (acidic) keratins. it is possible that epidermal K14 may function as an inhibitor of TNF–TNFR1 signaling through an association with TRADD.	SIGNOR-251907
P12931	Q14258	1	phosphorylation	up-regulates activity	0.271	Here, we demonstrated that TRIM25 interacted with c-Src and underwent tyrosine phosphorylation by c-Src kinase upon viral infection and the phosphorylation is required for the complete activation of RIG-I signaling. Analysis using a c-Src inhibitor and TRIM25 mutant, in which tyrosine 278 is substituted by phenylalanine (Y278F), suggested that the phosphorylation positively regulates K63-linked polyubiquitination of RIG-I and subsequent antiviral signaling.	SIGNOR-277405
Q13129	Q13671	2	binding	up-regulates activity	0.2	Rit and Rin were found to interact with the known Ras binding proteins RalGDS, Rlf, and AF-6/Canoe. These interactions were GTP and effector domain dependent and suggest that RalGDS, Rlf, and AF-6 are Rit and Rin effectors.	SIGNOR-220920
P23458	Q06124	1	phosphorylation	up-regulates activity	0.768	Tyrosine residues 304 and 327 in shp-2 are phosphorylated by jaks, and phosphorylated shp-2 can associate with the downstream adapter protein grb2	SIGNOR-236274
P18848	Q9BW92	1	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-269428
Q9NY46	Q92915	2	binding	down-regulates activity	0.244	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-253445
P63027	Q8WXE9	2	binding	up-regulates quantity	0.564	the monomeric adaptor proteins AP180/CALM and stonin-2 are required for the efficient retrieval of synaptobrevin II (sybII) and synaptotagmin-1 respectively. Furthermore, recent studies have revealed that sybII and synaptotagmin-1 interact with other SV cargoes to ensure a high fidelity of retrieval.	SIGNOR-264113
O14986	P43405	0	phosphorylation	down-regulates activity	0.2	We identified spleen tyrosine kinase (Syk), which is activated by oxidants, as a candidate PIP5Kbeta kinase in this pathway, and mapped the oxidant-sensitive tyrosine phosphorylation site to residue 105. The PIP5KbetaY105E phosphomimetic is catalytically inactive and cytosolic, whereas the Y105F non-phosphorylatable mutant has higher intrinsic lipid kinase activity and is much more membrane associated than wild type PIP5Kbeta.	SIGNOR-276227
P11274	P01106	0	transcriptional regulation	up-regulates quantity by expression	0.362	In the present study we demonstrate that MYC and its partner MAX bind to the BCR promoter, leading to up-regulation of BCR and BCR/ABL1 at both transcriptional and protein levels.\|Here we describe a regulatory pathway modulating BCR and BCR/ABL1 expression, showing that the BCR promoter is under the transcriptional control of the MYC/MAX heterodimer.	SIGNOR-272144
Q15075	Q16539	0	phosphorylation	up-regulates activity	0.458	We found that p38alpha can phosphorylate the rab5 effectors eea1 and rabenosyn-5 on thr-1392 and ser-215, respectively, and these phosphorylation events regulate the recruitment of eea1 and rabenosyn-5 to membranes	SIGNOR-140082
Q96PU5	P35499	1	ubiquitination	down-regulates quantity by destabilization	0.279	The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).	SIGNOR-253460
Q92835	P29353	2	binding	up-regulates	0.696	The results indicate that ship, shc, and grb2 form a ternary complex in stimulated b cells, with grb2 stabilizing the interaction between shc and ship. The interactions between shc, grb2, and ship are therefore analogous to the interactions between shc, grb2, and sos. Shc and grb2 may help to localize ship to the cell membrane, regulating ship's inhibitory function following bcr stimulation.	SIGNOR-66949
Q9Y625	Q13635	2	binding	up-regulates activity	0.35	Based on results from in vitro experiments, we had previously proposed that GPC6 stimulates Hh signaling by interacting with Hh and Patched1 (Ptc1), and facilitating/stabilizing their interaction.	SIGNOR-264031
P04637	Q9BY41	0	deacetylation	down-regulates activity	0.456	HDAC8 mediates CM-induced deacetylation of p53.Collectively, these results indicate that although binding to p53 and HDAC8 occurs through distinct regions of the CM protein, simultaneous interaction with HDAC8 and p53 is required for aberrant deacetylation and inactivation of p53.	SIGNOR-255738
Q00535	O94811	1	phosphorylation	down-regulates activity	0.403	Here we show that TPPP induces tubulin self-assembly into intact frequently bundled microtubules, and that the phosphorylation of specific sites distinctly affects the function of TPPP. The phosphorylation sites Thr(14), Ser(18), Ser(160) for Cdk5; Ser(18), Ser(160) for ERK2, and Ser(32) for PKA were identified by mass spectrometry. The phosphorylation by ERK2 or Cdk5 resulted in the loss of microtubule-assembling activity of TPPP.	SIGNOR-262931
Q9NQS5	P09471	2	binding	up-regulates activity	0.25	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256983
Q9Y2A7	Q6T4R5	2	binding	up-regulates activity	0.2	We show that the WHD of NHS interacts with the Abi family of proteins, HSPC300, Nap1 and Sra1, and is important for the localization of NHS to the leading edge.	SIGNOR-253576
P05771	P16949	1	phosphorylation	down-regulates	0.2	Op18 is multisite phosphorylated on four ser residues during mitosis;two of these ser residues, ser-25 and ser-38, are targets for cyclin-dependent protein kinases. our findings suggest that stathmin phosphorylation in reh6 cells could be in part mediated by pkc activation.	SIGNOR-50598
Q07666	Q92793	2	binding	down-regulates activity	0.379	These results suggest that Sam68 and CBP interact in vivo in a manner dependent on the FXE/DXXXL motif. Sam68 Represses CBP-dependent Transcriptional Activation	SIGNOR-266202
Q96EV8	Q9Y6W5	2	binding	up-regulates activity	0.343	Dysbindin-1, WAVE2 and Abi-1 form a complex that regulates dendritic spine formation. Although dysbindin-1, WAVE2 and Abi-1 form a ternary complex, dysbindin-1 promoted the binding of WAVE2 to Abi-1.	SIGNOR-265659
O60716	P28827	0	dephosphorylation	down-regulates quantity	0.541	Specifically, RPTP\u03bc dephosphorylated p120 catenin, subsequently leading to a lower level of cytoplasmic protein compared with that observed with the vector control and RPTP\u03bc-CS.	SIGNOR-277042
P62837	P50542	1	ubiquitination	down-regulates quantity by destabilization	0.416	Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle.	SIGNOR-253023
Q7L804	Q7KZI7	0	phosphorylation	up-regulates	0.42	We identified the kinase that phosphorylated rab11-fip2 as mark2/emk1/par-1balpha (mark2), and recombinant mark2 phosphorylated rab11-fip2 only on serine 227. In calcium switch assays, cells expressing rab11-fip2(s227a) showed a defect in the timely reestablishment of p120-containing junctional complexes.	SIGNOR-147118
P17612	O43665	1	phosphorylation	down-regulates activity	0.334	We report in this study the acute functional regulation of rgs10 thru the specific and inducible phosphorylation of rgs10 protein at serine 168 by camp-dependent kinase a. This phosphorylation nullifies the rgs10 activity at the plasma membrane, which controls the g protein-dependent activation of the inwardly rectifying potassium channel.	SIGNOR-109173
P59594	P11226	2	binding	down-regulates activity	0.2	We have demonstrated that MBL selectively binds to SARS-S pseudotyped virus and can inhibit SARS-CoV infection in susceptible cell lines. Our results identified a single N-linked glycosylation site, N330, on S glycoprotein as the target for the specific interactions between MBL and SARS-CoV and provide evidence that the viral interaction with MBL did not affect its interaction with the ACE2 receptor. Binding to MBL did not affect SARS-S interactions with the ACE2 receptor. Furthermore, MBL-mediated inhibition occurred at a step prior to CTSL-mediated activation of SARS-S fusion. Thus, we suggest that the binding of the MBL may interfere with the induction of conformational changes within the S glycoprotein and thus prevent an early, postreceptor-binding event.	SIGNOR-260285
P11142	P13569	2	binding	down-regulates quantity	0.672	JB12 cooperates with cytosolic Hsc70 and the ubiquitin ligase RMA1 to target CFTR and CFTRΔF508 for degradation. JB12 drives Hsc70 to associate with CFTR and the RMA1 E3 complex	SIGNOR-271492
O94901	P49790	2	binding	up-regulates activity	0.43	The NXF1:NXT1 complex and NUP153 interact with the amino terminus of SUN1 \|In analogy to a proposal made by Chang et al.4, Nesprins could help anchoring SUN1 near the NPC to enable it to fulfill its task in mRNA export.	SIGNOR-263294
Q96T68	P68431	1	methylation	up-regulates activity	0.2	Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression.	SIGNOR-263896
P35222	P49789	2	binding	down-regulates	0.509	Fhit interacts with _-catenin in vitro and in vivo / the tumor suppressor fhit acts as a repressor of _-catenin transcriptional activity	SIGNOR-159873
Q8NI17	P23458	2	binding	up-regulates	0.497	Il-31 can activate janus kinase (jak) 1 and jak2 signaling molecules after binding to its receptor complex.	SIGNOR-161342
Q14653	P13288	0	phosphorylation	down-regulates activity	0.2	BGLF4 kinase interacts physically with and phosphorylates IRF3, which is the initial activator of transcription in the innate immune response. BGLF4 suppresses IRF3-dependent transcriptional activation. Data here suggest that Ser123, Ser173, and Thr180 contribute additively to the BGLF4-mediated repression of the IRF3 transactivation activity.	SIGNOR-266647
P10588	P22888	1	transcriptional regulation	down-regulates quantity by repression	0.302	Functional analysis showed that EAR2 and EAR3/COUP-TFI repressed the hLHR promoter activity, whereas TR4 activated hLHR gene transcription.	SIGNOR-266216
P14317	P43405	0	phosphorylation	up-regulates	0.667	Here, we show that bcr-associated tyrosine kinases lyn and syk synergistically phosphorylate hs1, and that tyr-378 and tyr-397 of hs1 are the critical residues for its bcr-induced phosphorylation. once the two tyrosine residues are both phosphorylated, processive phosphorylation of hs1 by lyn and the other src family kinases would take place, producing hyperphosphorylated form of hs1. Finally, it is this hyperphosphorylated form of hs1 that translocates to the nucleus and activates b cell apoptosis.	SIGNOR-47342
P53396	O14874	0	phosphorylation	up-regulates activity	0.2	BCKDK can activate ACLY and promote the cleavage of citric acid into acetyl-CoA, and oxaloacetate.\|BCKDK can phosphorylate BCKDHA and ATP citrate lyase (ACLY), exerting opposing effects on both.	SIGNOR-280194
O00459	Q13191	0	ubiquitination	down-regulates activity	0.499	Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells. it can be postulated that Cbl-b, as an E3 Ub ligase, may play a general role in functional regulation of its target proteins through ubiquitination in a protein degradation-independent manner.	SIGNOR-271424
P53350	P00519	0	phosphorylation	up-regulates activity	0.29	C-ABL can directly phosphorylate PLK1 and activate PLK1. \| The above results indicate that c-ABL–mediated PLK1 Y425 phosphorylation regulates PLK1 ubiquitination and stability.	SIGNOR-260935
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
Q13451	P04150	2	binding	down-regulates	0.745	When not associated with glucocorticoids, glucocorticoid receptors are predominantly found in the cytoplasm as part of a multimeric molecular chaperone complex that includes several heat shock proteins (HSPs), such as HSP70 and HSP90, the HSP90_binding protein p23 (also known as PTGES3) and proteins that help to bind HSP90 such as FK506_binding protein 5 (FKBP5).	SIGNOR-251666
Q96ST3	Q13886	2	binding	up-regulates activity	0.445	detailed biochemical and functional analyses have demonstrated that the TIEG2 _-HRM domain interacts specifically with the PAH2 domain of mSin3A to repress transcription. our data suggest the presence of a conserved _-helical repression motif (_-HRM) in the TIEG and BTEB subfamilies of Sp1-like proteins that mediates transcriptional repression activity through interaction with the corepressor mSin3A.	SIGNOR-222434
P60953	O60890	0	gtpase-activating protein	up-regulates activity	0.637	OPHN-1 colocalized with the actin cytoskeleton in neuronal and glial cells. We have previously shown that OPHN1 stimulates GTPases activity of RhoA, Cdc42, and Rac1 in vitro	SIGNOR-268398

O75461

O14757

0

phosphorylation

down-regulates activity

0.574

the checkpoint kinase Chk1 phosphorylates E2F6 leading to its dissociation from promoters.

SIGNOR-266371

P41279

Q02750

1

phosphorylation

up-regulates

0.574

Activation of mek family kinases requires phosphorylation of two conserved ser/thr residues.Phosphopeptide analysis demonstrated that serine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf

SIGNOR-36453

P20749

O15379

2

binding

up-regulates

0.348

We show that bcl-3 is a substrate for the protein kinase gsk3 and that gsk3-mediated bcl-3 phosphorylation, which is inhibited by akt activation, targets its degradation through the proteasome pathway. This phosphorylation modulates its association with hdac1, 3 and 6.

SIGNOR-129804

P06493

P55211

1

phosphorylation

down-regulates

0.429

Here, we show that the apoptotic initiator protease caspase-9 is regulated during the cell cycle through periodic phosphorylation at an inhibitory site, thr125. This site is phosphorylated by cdk1/cyclin b1 during mitosis and in response to microtubule poisons that arrest cells at this stage of the cell cycle.

SIGNOR-141621

P53350

O00139

1

phosphorylation

up-regulates activity

0.684

Taken together, KIF2A is phosphorylated at T554 by PLK1 in the subdistal appendages of the mother centriole, which enhances MT depolymerization to disassemble primary cilia in a growth-signal-dependent manner.|Thus, PLK1 and APC/C mediated dual regulation connect the MT depolymerizing activity of KIF2A to a physiological primary cilia disassembly during the proliferative phase.

SIGNOR-278380

O00327

P49841

0

phosphorylation

down-regulates

0.382

Gsk3beta phosphorylates bmal1 specifically on ser 17 and thr 21 and primes it for ubiquitylation. In the absence of gsk3beta-mediated phosphorylation, bmal1 becomes stabilized and bmal1 dependent circadian gene expression is dampened.

SIGNOR-162786

Q14934

Q9Y625

1

transcriptional regulation

up-regulates quantity by expression

0.2

NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype.

SIGNOR-264023

Q8N6U8

O75386

0

relocalization

up-regulates activity

0.608

Upon knockdown of Tulp3 using siRNA in IMCD3 cells, ciliary localization of Gpr161 was severely reduced

SIGNOR-259938

Q6PIY7

P22694

0

phosphorylation

down-regulates activity

0.2

We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition.

SIGNOR-259403

O43293

O14950

1

phosphorylation

up-regulates

0.511

Hzipk phosphorylated the regulatory light chain of myosin ii (mrlc) at both ser19 and thr18 in vitro. Phosphorylation of mrlc is required to generate the driving force in the migration of the cells but not necessary for localization of myosin ii at the leading edge.

SIGNOR-16043

P35222

P15884

2

binding

up-regulates activity

0.69

beta-catenin interacts with the TCF/Lef family transcription factors.

SIGNOR-178042

Q13261

P40933

2

binding

up-regulates

0.868

Interleukin-15 specificity and high affinity binding are conferred by the IL-5-specific but nonsignaling IL-15R alpha subunit, which is structurally similar (but not homologous) to the alpha receptor subunit of IL-2

SIGNOR-157415

Q9HBY8

O15530

0

phosphorylation

up-regulates activity

0.596

SGK2 and SGK3 are activated in vitro by PDK1, albeit more slowly than SGK1, and their activation is accompanied by the phosphorylation of Thr(193) and Thr(253) respectively. The PDK1-catalysed phosphorylation and activation of SGK2 and SGK3, like SGK1, is greatly potentiated by mutating Ser(356) and Ser(419) respectively to Asp, these residues being equivalent to the C-terminal phosphorylation site of PKB.

SIGNOR-250277

P49841

P22415

1

phosphorylation

up-regulates activity

0.286

Both MITF and USF1 were activated by glycogen synthase kinase (GSK) 3, with GSK3 phosphorylation sites on USF1 identified as the previously described activating site threonine 153 as well as serine 186.

SIGNOR-276355

P68400

P78344

1

phosphorylation

up-regulates activity

0.226

DAP5(S902) is phosphorylated by CK2α. Phosphorylation of DAP5(S902) by CK2α is required for eIF2β binding.

SIGNOR-266384

Q16254

O15392

1

transcriptional regulation

down-regulates quantity by repression

0.334

This TGF-beta response is triggered through a Smad2/3-dependent hypophosphorylation of Rb and the subsequent association of the Rb/E2F4 repressive complex to CDE/CHR elements in the proximal region of the survivin promoter.

SIGNOR-271678

Q6DKK2

Q9H1H9

2

binding

up-regulates activity

0.432

We show that PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26), and its binding partner TTC19, which in turn interacts with CHMP4B, an endosomal sorting complex required for transport (ESCRT)-III subunit implicated in the abscission step of cytokinesis. On the basis of these data and the high-content microscopy described above, we propose that PtdIns(3)P controls the KIF13A-dependent recruitment of FYVE-CENT and TTC19 to the midbody, and that TTC19 is the most downstream effector of the three, possibly controlling the function of CHMP4B.

SIGNOR-265540

Q13153

O95863

1

phosphorylation

up-regulates

0.4

Pak1 regulates the repressor activity of snail by phosphorylating on ser(246). Pak1 phosphorylation of snail supports snail's accumulation in the nucleus as well as its repressor functions.

SIGNOR-135605

Q9UNH5

P30305

1

dephosphorylation

down-regulates activity

0.56

Cdc14A inhibits Cdc25A and Cdc25B activity, the latter through direct binding and dephosphorylation ( ).|Together, these data indicate that Cdc14A dephosphorylates Cdc25B, inhibiting its catalytic activity.

SIGNOR-276968

Q6ZUM4

P63000

1

gtpase-activating protein

down-regulates activity

0.589

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-260482

P11802

P30304

0

dephosphorylation

up-regulates activity

0.705

Invalidation of CDK4 has no impact by itself on the cell proliferation, but invalidation of CDC25A prevents the dephosphorylation of CDK6 (Y24) and CDK4 (Y17) residues, and impedes their association with CCNDs.

SIGNOR-267568

Q13315

Q15911

1

phosphorylation

up-regulates activity

0.346

Indeed, ATM phosphorylates ATBF1 at Ser1180 in HEK293T cells exposed to 10-Gy radiation [ xref ].|We also found in this study that ATBF1 mediated neuronal death is dependent on ATM signals because the blockage of ATM by treatment with ATM inhibitors, caffeine and KU55933, abolished ATBF1 functions in neuronal death.

SIGNOR-279138

Q05639

P15056

0

phosphorylation

down-regulates quantity by destabilization

0.326

Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B- and C-Raf.

SIGNOR-276406

Q96B36

P31749

0

phosphorylation

down-regulates activity

0.782

Treatment of these cells with 4-hydroxytamoxifen stimulated the phosphorylation of wt PRAS40 but not the mutant PRAS40 in which Thr-246 was mutated. These results demonstrate that activation of Akt alone is sufficient to induce phosphorylation of PRAS40

SIGNOR-252544

P07948

Q96P20

1

phosphorylation

down-regulates

0.29

Lyn phosphorylates NLRP3 at Tyr 918 and controls NLRP3 ubiquitination.|Therefore, our data collectively indicate that Lyn inhibits the NLRP3 inflammasome in vivo.

SIGNOR-278485

Q96S53

P23528

1

phosphorylation

down-regulates activity

0.503

Like tesk1, tesk2 phosphorylated cofilin specifically at ser-3 and induced formation of actin stress fibers and focal adhesions.

SIGNOR-108753

P04637

O15111

0

phosphorylation

up-regulates activity

0.429

In the nucleus, IKKalpha enhances p53 mediated GADD45 and BAD gene expressions by phosphorylating p53 at Ser20 and stabilizing p53 protein levels , leading to the induction of apoptosis in response to ROS exposure.|PKC-activated nuclear I\u03baB kinase\u03b1 promotes the stability of p53 protein and mediates reactive oxygen species-induced apoptosis [ ].

SIGNOR-280231

P55957

P68400

0

phosphorylation

up-regulates activity

0.286

Here we report that Bid is phosphorylated by casein kinase I (CKI) and casein kinase II (CKII). Inhibition of CKI and CKII accelerated Fas-mediated apoptosis and Bid cleavage, whereas hyperactivity of the kinases delayed apoptosis. | These results suggest that residues S61, S64, and to a much lesser extent T58 are sites of phosphorylation of Bid.

SIGNOR-250831

P49840

P31751

0

phosphorylation

down-regulates

0.557

Activated pi3k/akt pathway results in inhibitory phosphorylation of gsk3

SIGNOR-138179

P06493

P51003

1

phosphorylation

up-regulates activity

0.258

Once an oocyte resumes meiosis, activated CDK1 and ERK1/2 cooperatively mediate the phosphorylation of three serine residues of PAPalpha, 537, 545 and 558, thereby leading to increased activity.

SIGNOR-268338

P46695

Q13362

2

binding

down-regulates

0.542

Iex-1 binds to b56 subunits and perk independently, enhances b56 phosphorylation by erk at a conserved ser/pro site in this complex and triggers dissociation from the catalytic subunit.

SIGNOR-144309

Q4V328

P42574

0

cleavage

up-regulates activity

0.414

These results suggest that the region of GRASP‐1 downstream of the Caspase‐3‐cleavage site is capable of activating the JNK signaling pathway by enhancing the phosphorylation of JNK. these results suggest that full length GRASP‐1 does not enhance JNK pathway activity, possibly due to the inhibitory effect of the N‐terminal fragment on the C‐terminal fragment. In contrast, Caspase‐3 cleavage of GRASP‐1 releases the C‐terminal fragment, which in turn activates JNK signaling by serving as a scaffold protein.

SIGNOR-260641

Q96DT5

Q96M91

2

binding

up-regulates activity

0.2

CFAP53 likely facilitates the transport of TTC25 and the dyneins into cilia. CFAP53 at the centriolar satellites may form a complex with TTC25 and ODAs, including DNAH5 and DNAH11, and regulate their trafficking into the cilium (Fig 10B).

SIGNOR-265545

Q86UX7

P05106

2

binding

up-regulates activity

0.65

Mechanistically, Kindlin-3 can directly bind to regions of beta-integrin tails distinct from those of Talin and trigger integrin activation. We have therefore identified Kindlin-3 as a novel and essential element for platelet integrin activation in hemostasis and thrombosis|Kindlin-3 was also able to interact with the wild-type beta1 and beta3 integrin tails (Fig. 3c), in the presence and absence of Talin1 (Supplementary Fig. 3 online), and the F3 subdomain of Kindlin-3 was sufficient for this interaction and this interaction occurred in a direct manner

SIGNOR-266066

P48169

Q8TAB3

2

binding

up-regulates quantity by stabilization

0.2

Here, we found that PCDH19 binds the alpha subunits of GABAAR and regulates its surface availability and currents in cultured hippocampal neurons. The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated. Here, we identified a new interaction between PCDH19 and GABAA receptor (GABAAR) alpha subunits in the rat brain. PCDH19 shRNA-mediated downregulation reduces GABAAR surface expression and affects the frequency and kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in cultured hippocampal neurons.

SIGNOR-267220

Q86U70

Q9NVW2

0

polyubiquitination

down-regulates quantity by destabilization

0.566

Here we identify RLIM as a ubiquitin protein ligase that is able to target CLIM cofactors for degradation through the 26S proteasome pathway.

SIGNOR-272617

P25116

O95837

2

binding

up-regulates activity

0.439

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-257293

Q16665

Q96KS0

0

hydroxylation

down-regulates quantity by destabilization

0.856

There are three EglN family members in humans and mice (EglN1, EglN2, and EglN3). Their enzymatic activity requires oxygen, ascorbic acid, iron, and α-ketoglutarate (α-KG). Under hypoxic conditions, EglNs lose their activity and fail to hydroxylate HIFα, which leads to HIFα stabilization

SIGNOR-261999

Q9P2P5

O15350

1

ubiquitination

up-regulates quantity by stabilization

0.37

P73 was efficiently ubiquitinated but stabilized in a NEDL2-dependent manner. Accordingly, p73 decayed at faster rates in the absence of NEDL2 than in its presence. Consistent with the NEDL2-mediated stabilization of p73, NEDL2 enhanced the p73-dependent transcriptional activation. Thus, our results suggest that NEDL2 activates the function of p73 by increasing its stability.

SIGNOR-269457

P11309

Q96T88

1

phosphorylation

down-regulates quantity by destabilization

0.2

Here we report that UHRF1 is a novel substrate of PIM1 kinase, which could be phosphorylated at Ser311 and therefore promoted to degradation.

SIGNOR-277349

P27361

Q07820

1

phosphorylation

up-regulates

0.436

We then showed that erk could phosphorylate mcl-1 at two consensus residues, thr 92 and 163, which is required for the association of mcl-1 and pin1, resulting in stabilization of mcl-1.

SIGNOR-179812

P06493

P08670

1

phosphorylation

down-regulates

0.362

These results strongly suggest that cdc2 kinase is the kinase which phosphorylates vimentin ser55 in the entire cytoplasm during mitosis and that the appearance of immunoreactivities with antibody 4a4 in cell staining indeed reflect the vimentin phosphorylation by cdc2 kinase. immunofluorescent evidence using antibody 4a4 and biochemical analysis using vimentin ser55 peptide showed that the degree of disassembly of vimentin filament of various cell types at early mitotic phase correlated well with the amount of mitotically activated cdc2 kinase.

SIGNOR-35492

P19086

P55085

2

binding

up-regulates activity

0.334

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-257232

P23443

O00418

1

phosphorylation

down-regulates activity

0.736

We show that two such kinases, p70 s6 kinase (regulated via mtor) and p90(rsk1) (activated by erk), phosphorylate eef2k at a conserved serine and inhibit its activity

SIGNOR-109712

O00308

P11161

1

ubiquitination

down-regulates quantity

0.372

The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-induced T-cell death by catalyzing EGR2 ubiquitination|AIP2 interacts with and promotes ubiquitin-mediated degradation of EGR2, a zinc finger transcription factor that has been found to regulate Fas ligand (FasL) expression during activation-induced T-cell death.

SIGNOR-268849

P01106

P17480

1

transcriptional regulation

up-regulates quantity by expression

0.356

MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation|MAD1 repressed and c-MYC activated rDNA transcription in nuclear run-on assays. Repression of rDNA transcription by MAD1 was associated with its ability to interact directly with the promoter of upstream binding factor (UBF), an rDNA regulatory factor. Conversely, c-MYC activated transcription from the UBF promoter.

SIGNOR-269644

Q14344

O43614

2

binding

up-regulates activity

0.25

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

SIGNOR-257350

Q13470

Q96L34

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-273865

P68400

Q92598

1

phosphorylation

down-regulates activity

0.329

Protein kinase CK2 phosphorylates Hsp105 alpha at Ser509 and modulates its function. | the phosphorylation of Hsp105 alpha at Ser(509) abolished the inhibitory activity of Hsp105 alpha in vitro.

SIGNOR-250901

O00631

O14983

2

binding

down-regulates activity

0.55

These results suggest that sAnk1 interacts with SLN both directly and in complex with SERCA1 and reduces SLN's inhibitory effect on SERCA1 activity.

SIGNOR-265929

P06493

Q9Y2I6

1

phosphorylation

down-regulates quantity by destabilization

0.422

In this study, we show that Nlp can be phosphorylated by cell cycle protein kinase Cdc2/cyclin B1. The phosphorylation sites of Nlp are mapped at Ser185 and Ser589. the phosphorylation at the site Ser589 by Cdc2/cyclin B1 plays an important role in Nlp protein stability probably due to its effect on protein degradation.

SIGNOR-259831

P31749

Q16584

1

phosphorylation

down-regulates

0.4

Negative regulation of mixed lineage kinase 3 by protein kinase b/akt leads to cell survivalthe expression of activated akt1 inhibits mlk3-mediated cell death in a manner dependent on serine 674 phosphorylation.

SIGNOR-252592

O15355

P84103

1

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

P09471

P25101

2

binding

up-regulates activity

0.272

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-257253

Q12923

P06213

1

dephosphorylation

down-regulates

0.26

We demonstrate that ptpl1, like ptp1b, interacts with and dephosphorylates a bis-phosphorylated insulin receptor peptide more efficiently than monophosphorylated peptides, indicating that ptpl1 may down-regulate the phosphatidylinositol 3-kinase pathway, by dephosphorylating insulin or growth factor receptors that contain tandem phosphotyrosines.

SIGNOR-132555

P06730

Q9UDX5

1

translation regulation

up-regulates activity

0.2

In this study, we demonstrate that mTORC1 stimulates mitochondrial fission via 4E-BP-mediated translational regulation of the mitochondrial fission factor MTFP1. Suppression of mTORC1 activity by pharmacological or genetic means causes mitochondrial hyperfusion, branching, and circularization. This is a consequence of downregulation of MTFP1 levels via the mTORC1/4E-BP pathway, thereby eliciting changes in phosphorylation and localization of the mitochondrial fission factor DRP1

SIGNOR-275429

Q9UBE8

P46937

1

phosphorylation

up-regulates activity

0.2

Here, we report that osmotic stress stimulates transient YAP nuclear localization and increases YAP activity even when YAP Ser127 is phosphorylated. Osmotic stress acts via the NLK kinase to induce YAP Ser128 phosphorylation. Phosphorylation of YAP at Ser128 interferes with its ability to bind to 14-3-3, resulting in YAP nuclear accumulation and induction of downstream target gene expression.

SIGNOR-273909

Q8IU57

P23458

2

binding

up-regulates

0.78

Each r1-type chain (il-10r1, il-20r1, il-22r1, ifn-_r1 and ifn-_r1) is associated with jak1 tyrosine kinase and mediates recruitment of a variety of signaling molecules after being phosphorylated on its intracellular domain.

SIGNOR-124480

O00470

P28358

2

binding

up-regulates activity

0.375

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

SIGNOR-241226

Q8IZP0

P28482

0

phosphorylation

up-regulates

0.445

Our mass spectrometry also identified abi1 s183 and s225 on abi1 (numbering corresponds to abi1 isoform 1) as sites phosphorylated on endogenous protein and in the wildtype erk-dependent in vitro phosphorylated sample. these data indicate erk phosphorylation of abi1 is required for basal and egf-induced wrc interaction with the wrp2/3 complex.

SIGNOR-172873

P02533

Q15628

2

binding

down-regulates activity

0.346

TRADD specifically bound K18 and K14, type I (acidic) keratins. it is possible that epidermal K14 may function as an inhibitor of TNF–TNFR1 signaling through an association with TRADD.

SIGNOR-251907

P12931

Q14258

1

phosphorylation

up-regulates activity

0.271

Here, we demonstrated that TRIM25 interacted with c-Src and underwent tyrosine phosphorylation by c-Src kinase upon viral infection and the phosphorylation is required for the complete activation of RIG-I signaling. Analysis using a c-Src inhibitor and TRIM25 mutant, in which tyrosine 278 is substituted by phenylalanine (Y278F), suggested that the phosphorylation positively regulates K63-linked polyubiquitination of RIG-I and subsequent antiviral signaling.

SIGNOR-277405

Q13129

Q13671

2

binding

up-regulates activity

0.2

Rit and Rin were found to interact with the known Ras binding proteins RalGDS, Rlf, and AF-6/Canoe. These interactions were GTP and effector domain dependent and suggest that RalGDS, Rlf, and AF-6 are Rit and Rin effectors.

SIGNOR-220920

P23458

Q06124

1

phosphorylation

up-regulates activity

0.768

Tyrosine residues 304 and 327 in shp-2 are phosphorylated by jaks, and phosphorylated shp-2 can associate with the downstream adapter protein grb2

SIGNOR-236274

P18848

Q9BW92

1

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-269428

Q9NY46

Q92915

2

binding

down-regulates activity

0.244

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-253445

P63027

Q8WXE9

2

binding

up-regulates quantity

0.564

the monomeric adaptor proteins AP180/CALM and stonin-2 are required for the efficient retrieval of synaptobrevin II (sybII) and synaptotagmin-1 respectively. Furthermore, recent studies have revealed that sybII and synaptotagmin-1 interact with other SV cargoes to ensure a high fidelity of retrieval.

SIGNOR-264113

O14986

P43405

0

phosphorylation

down-regulates activity

0.2

We identified spleen tyrosine kinase (Syk), which is activated by oxidants, as a candidate PIP5Kbeta kinase in this pathway, and mapped the oxidant-sensitive tyrosine phosphorylation site to residue 105. The PIP5KbetaY105E phosphomimetic is catalytically inactive and cytosolic, whereas the Y105F non-phosphorylatable mutant has higher intrinsic lipid kinase activity and is much more membrane associated than wild type PIP5Kbeta.

SIGNOR-276227

P11274

P01106

0

transcriptional regulation

up-regulates quantity by expression

0.362

In the present study we demonstrate that MYC and its partner MAX bind to the BCR promoter, leading to up-regulation of BCR and BCR/ABL1 at both transcriptional and protein levels.|Here we describe a regulatory pathway modulating BCR and BCR/ABL1 expression, showing that the BCR promoter is under the transcriptional control of the MYC/MAX heterodimer.

SIGNOR-272144

Q15075

Q16539

0

phosphorylation

up-regulates activity

0.458

We found that p38alpha can phosphorylate the rab5 effectors eea1 and rabenosyn-5 on thr-1392 and ser-215, respectively, and these phosphorylation events regulate the recruitment of eea1 and rabenosyn-5 to membranes

SIGNOR-140082

Q96PU5

P35499

1

ubiquitination

down-regulates quantity by destabilization

0.279

The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).

SIGNOR-253460

Q92835

P29353

2

binding

up-regulates

0.696

The results indicate that ship, shc, and grb2 form a ternary complex in stimulated b cells, with grb2 stabilizing the interaction between shc and ship. The interactions between shc, grb2, and ship are therefore analogous to the interactions between shc, grb2, and sos. Shc and grb2 may help to localize ship to the cell membrane, regulating ship's inhibitory function following bcr stimulation.

SIGNOR-66949

Q9Y625

Q13635

2

binding

up-regulates activity

0.35

Based on results from in vitro experiments, we had previously proposed that GPC6 stimulates Hh signaling by interacting with Hh and Patched1 (Ptc1), and facilitating/stabilizing their interaction.

SIGNOR-264031

P04637

Q9BY41

0

deacetylation

down-regulates activity

0.456

HDAC8 mediates CM-induced deacetylation of p53.Collectively, these results indicate that although binding to p53 and HDAC8 occurs through distinct regions of the CM protein, simultaneous interaction with HDAC8 and p53 is required for aberrant deacetylation and inactivation of p53.

SIGNOR-255738

Q00535

O94811

1

phosphorylation

down-regulates activity

0.403

Here we show that TPPP induces tubulin self-assembly into intact frequently bundled microtubules, and that the phosphorylation of specific sites distinctly affects the function of TPPP. The phosphorylation sites Thr(14), Ser(18), Ser(160) for Cdk5; Ser(18), Ser(160) for ERK2, and Ser(32) for PKA were identified by mass spectrometry. The phosphorylation by ERK2 or Cdk5 resulted in the loss of microtubule-assembling activity of TPPP.

SIGNOR-262931

Q9NQS5

P09471

2

binding

up-regulates activity

0.25

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

SIGNOR-256983

Q9Y2A7

Q6T4R5

2

binding

up-regulates activity

0.2

We show that the WHD of NHS interacts with the Abi family of proteins, HSPC300, Nap1 and Sra1, and is important for the localization of NHS to the leading edge.

SIGNOR-253576

P05771

P16949

1

phosphorylation

down-regulates

0.2

Op18 is multisite phosphorylated on four ser residues during mitosis;two of these ser residues, ser-25 and ser-38, are targets for cyclin-dependent protein kinases. our findings suggest that stathmin phosphorylation in reh6 cells could be in part mediated by pkc activation.

SIGNOR-50598

Q07666

Q92793

2

binding

down-regulates activity

0.379

These results suggest that Sam68 and CBP interact in vivo in a manner dependent on the FXE/DXXXL motif. Sam68 Represses CBP-dependent Transcriptional Activation

SIGNOR-266202

Q96EV8

Q9Y6W5

2

binding

up-regulates activity

0.343

Dysbindin-1, WAVE2 and Abi-1 form a complex that regulates dendritic spine formation. Although dysbindin-1, WAVE2 and Abi-1 form a ternary complex, dysbindin-1 promoted the binding of WAVE2 to Abi-1.

SIGNOR-265659

O60716

P28827

0

dephosphorylation

down-regulates quantity

0.541

Specifically, RPTP\u03bc dephosphorylated p120 catenin, subsequently leading to a lower level of cytoplasmic protein compared with that observed with the vector control and RPTP\u03bc-CS.

SIGNOR-277042

P62837

P50542

1

ubiquitination

down-regulates quantity by destabilization

0.416

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

SIGNOR-253023

Q7L804

Q7KZI7

0

phosphorylation

up-regulates

0.42

We identified the kinase that phosphorylated rab11-fip2 as mark2/emk1/par-1balpha (mark2), and recombinant mark2 phosphorylated rab11-fip2 only on serine 227. In calcium switch assays, cells expressing rab11-fip2(s227a) showed a defect in the timely reestablishment of p120-containing junctional complexes.

SIGNOR-147118

P17612

O43665

1

phosphorylation

down-regulates activity

0.334

We report in this study the acute functional regulation of rgs10 thru the specific and inducible phosphorylation of rgs10 protein at serine 168 by camp-dependent kinase a. This phosphorylation nullifies the rgs10 activity at the plasma membrane, which controls the g protein-dependent activation of the inwardly rectifying potassium channel.

SIGNOR-109173

P59594

P11226

2

binding

down-regulates activity

0.2

We have demonstrated that MBL selectively binds to SARS-S pseudotyped virus and can inhibit SARS-CoV infection in susceptible cell lines. Our results identified a single N-linked glycosylation site, N330, on S glycoprotein as the target for the specific interactions between MBL and SARS-CoV and provide evidence that the viral interaction with MBL did not affect its interaction with the ACE2 receptor. Binding to MBL did not affect SARS-S interactions with the ACE2 receptor. Furthermore, MBL-mediated inhibition occurred at a step prior to CTSL-mediated activation of SARS-S fusion. Thus, we suggest that the binding of the MBL may interfere with the induction of conformational changes within the S glycoprotein and thus prevent an early, postreceptor-binding event.

SIGNOR-260285

P11142

P13569

2

binding

down-regulates quantity

0.672

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

SIGNOR-271492

O94901

P49790

2

binding

up-regulates activity

0.43

The NXF1:NXT1 complex and NUP153 interact with the amino terminus of SUN1 |In analogy to a proposal made by Chang et al.4, Nesprins could help anchoring SUN1 near the NPC to enable it to fulfill its task in mRNA export.

SIGNOR-263294

Q96T68

P68431

1

methylation

up-regulates activity

0.2

Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression.

SIGNOR-263896

P35222

P49789

2

binding

down-regulates

0.509

Fhit interacts with _-catenin in vitro and in vivo / the tumor suppressor fhit acts as a repressor of _-catenin transcriptional activity

SIGNOR-159873

Q8NI17

P23458

2

binding

up-regulates

0.497

Il-31 can activate janus kinase (jak) 1 and jak2 signaling molecules after binding to its receptor complex.

SIGNOR-161342

Q14653

P13288

0

phosphorylation

down-regulates activity

0.2

BGLF4 kinase interacts physically with and phosphorylates IRF3, which is the initial activator of transcription in the innate immune response. BGLF4 suppresses IRF3-dependent transcriptional activation. Data here suggest that Ser123, Ser173, and Thr180 contribute additively to the BGLF4-mediated repression of the IRF3 transactivation activity.

SIGNOR-266647

P10588

P22888

1

transcriptional regulation

down-regulates quantity by repression

0.302

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

SIGNOR-266216

P14317

P43405

0

phosphorylation

up-regulates

0.667

Here, we show that bcr-associated tyrosine kinases lyn and syk synergistically phosphorylate hs1, and that tyr-378 and tyr-397 of hs1 are the critical residues for its bcr-induced phosphorylation. once the two tyrosine residues are both phosphorylated, processive phosphorylation of hs1 by lyn and the other src family kinases would take place, producing hyperphosphorylated form of hs1. Finally, it is this hyperphosphorylated form of hs1 that translocates to the nucleus and activates b cell apoptosis.

SIGNOR-47342

P53396

O14874

0

phosphorylation

up-regulates activity

0.2

BCKDK can activate ACLY and promote the cleavage of citric acid into acetyl-CoA, and oxaloacetate.|BCKDK can phosphorylate BCKDHA and ATP citrate lyase (ACLY), exerting opposing effects on both.

SIGNOR-280194

O00459

Q13191

0

ubiquitination

down-regulates activity

0.499

Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells. it can be postulated that Cbl-b, as an E3 Ub ligase, may play a general role in functional regulation of its target proteins through ubiquitination in a protein degradation-independent manner.

SIGNOR-271424

P53350

P00519

0

phosphorylation

up-regulates activity

0.29

C-ABL can directly phosphorylate PLK1 and activate PLK1. | The above results indicate that c-ABL–mediated PLK1 Y425 phosphorylation regulates PLK1 ubiquitination and stability.

SIGNOR-260935

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

Q13451

P04150

2

binding

down-regulates

0.745

When not associated with glucocorticoids, glucocorticoid receptors are predominantly found in the cytoplasm as part of a multimeric molecular chaperone complex that includes several heat shock proteins (HSPs), such as HSP70 and HSP90, the HSP90_binding protein p23 (also known as PTGES3) and proteins that help to bind HSP90 such as FK506_binding protein 5 (FKBP5).

SIGNOR-251666

Q96ST3

Q13886

2

binding

up-regulates activity

0.445

detailed biochemical and functional analyses have demonstrated that the TIEG2 _-HRM domain interacts specifically with the PAH2 domain of mSin3A to repress transcription. our data suggest the presence of a conserved _-helical repression motif (_-HRM) in the TIEG and BTEB subfamilies of Sp1-like proteins that mediates transcriptional repression activity through interaction with the corepressor mSin3A.

SIGNOR-222434

P60953

O60890

0

gtpase-activating protein

up-regulates activity

0.637

OPHN-1 colocalized with the actin cytoskeleton in neuronal and glial cells. We have previously shown that OPHN1 stimulates GTPases activity of RhoA, Cdc42, and Rac1 in vitro

SIGNOR-268398