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
O95817	Q00535	0	phosphorylation	down-regulates quantity by destabilization	0.2	CDK5-mediated phosphorylation on S297 promotes BAG3 degradation.	SIGNOR-277502
P17252	Q86UR1	1	phosphorylation	down-regulates	0.29	Phosphorylation of nadph oxidase activator 1 (noxa1) on serine 282 by map kinases and on serine 172 by protein kinase c and protein kinase a prevents nox1 hyperactivation.	SIGNOR-163667
P30260	P06493	0	phosphorylation	up-regulates	0.704	Apc activation is thought to depend on apc phosphorylation and cdc20 binding. We have identified 43 phospho_sites on apc of which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts of apc1 and the tetratricopeptide repeat (tpr) subunits cdc27, cdc16, cdc23 and apc7. In vitro, at least 15 of the mitotic phospho_sites can be generated by cyclin_dependent kinase 1 (cdk1), and 3 by polo_like kinase 1 (plk1). Apc phosphorylation by cdk1, but not by plk1, is sufficient for increased cdc20 binding and apc activation	SIGNOR-119873
P04637	Q93009	0	deubiquitination	up-regulates	0.741	Hausp counteracts the destabilizing effect of mdm2 by direct deubiquitination of p53.	SIGNOR-139456
P23468	P40763	1	dephosphorylation	down-regulates activity	0.517	Transfection of wild-type PTPRD resulted in the specific dephosphorylation of STAT3 at tyrosine 705, a residue that must be phosphorylated for STAT3 to be active	SIGNOR-248442
O60229	Q8IW41	0	phosphorylation	up-regulates activity	0.385	The brain-specific nucleotide exchange factor kalirin-7 (Kal7) was identified as an MK5 interaction partner and substrate protein. The MK5 substrate Kal7, a Rho GEF and known activator of Rac GTPases, further contributes to PAK activation and actin filament reorganization. Thus, the coordinated phosphorylation of Borg proteins and Kal7 by ERK3 and MK5 constitute a novel signaling cascade involving feed-forward circuits, multiple GTPases, and cytoskeletal elements. The fragment SR3-6, but not the mutated fragment SR3-6-S487A, is phosphorylated by MK5.	SIGNOR-263093
P24723	P09211	1	phosphorylation	up-regulates activity	0.2	Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently	SIGNOR-276014
O95837	Q99677	2	binding	up-regulates activity	0.385	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-257432
P29317	P52797	2	binding	up-regulates	0.814	The eph family of receptors.	SIGNOR-52309
O95600	Q13351	0	transcriptional regulation	up-regulates quantity by expression	0.25	Here we report that Klf8 is repressed by Klf3 in vivo and is up-regulated by Klf1. Transcript analysis indicates that Klf8 has two promoters, both containing multiple CACCC elements. Transactivation assays and chromatin immunoprecipitation experiments indicate that Klf3 represses Klf8 directly and that Klf1 activates Klf8 directly.	SIGNOR-266050
Q15788	P27361	0	phosphorylation	up-regulates	0.268	Mapk also directly phosphorylates src-1 at thr1179 and ser1185. Phosphorylation of src-1 by mitogen-activated protein kinase (mapk) is required for optimal progesterone receptor-dependent transcription and for functional cooperation with camp response element-binding protein-binding protein	SIGNOR-91143
P10275	Q07912	0	phosphorylation	up-regulates activity	0.545	Ack1 interacted with and phosphorylated AR protein at Tyr 267 and Ack1 was shown to be required for optimal AR target gene expression and AR recruitment.\|Two intracellular tyrosine kinases, Ack1 (activated cdc42 associated kinase) and Src, phosphorylate and enhance AR activity and promote prostate xenograft tumor growth in castrated animals.	SIGNOR-278194
P23468	Q96NI6	2	binding	up-regulates activity	0.277	SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development. we identified LAR-RPTPs as novel ligands of SALM5 that mediates SALM5-dependent presynaptic differentiation in a splicing-dependent manner. Our data indicate that SALM5 interacts with all three known LAR-RPTPs—LAR, PTPδ, and PTPσ (Fig. 1).	SIGNOR-264086
Q9ULA0	Q13107	1	cleavage	down-regulates quantity by destabilization	0.2	A further analysis showed that the hydrolysis pathway contributes to DNPEP-mediated degradation of USP4 (Supporting Information Figs. S3A–S3F). The interaction between USP4 and DNPEP was confirmed by coIP assays	SIGNOR-275652
P06744	P68400	0	phosphorylation	down-regulates activity	0.333	It is known that human PGI/AMF is phosphorylated at Ser(185) by protein kinase CK2 (CK2) \| These results demonstrate that phosphorylation affects the allosteric kinetic properties of the enzyme, resulting in a less active form of PGI, whereas non-phosphorylated protein species retain cytokine activity.	SIGNOR-250869
O14654	Q8WYL5	2	binding	up-regulates activity	0.311	Insulin Receptor Substrate-4 Binds to Slingshot-1 Phosphatase and Promotes Cofilin Dephosphorylation. In addition, IRS4 co-localized with SSH1 in F-actin-rich membrane protrusions in insulin-stimulated cells, which suggests that the association of IRS4 with SSH1 contributes to localized activation of cofilin in membrane protrusions.	SIGNOR-277617
P31751	P49841	1	phosphorylation	down-regulates activity	0.623	Active AKT, a common mediator of cell survival signals induced by radiation through multiple intracellular signaling pathways,11, 12 suppresses apoptosis. AKT positively regulates cyclin D1 expression through inactivation of glycogen synthase kinase 3_ (GSK3_). The AKT-mediated phosphorylation of glycogen synthase kinase 3_ on serine9 decreases its kinase activity for Thr286 of cyclin D1, which inhibits the nuclear export and the cytoplasmic proteasomal degradation of cyclin D1	SIGNOR-245420
P15923	P49137	0	phosphorylation	up-regulates	0.52	Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2	SIGNOR-166643
P02461	P03956	0	cleavage	down-regulates quantity by destabilization	0.35	In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775–Ile776 or Gly775–Lys776 in native type I, II or III collagen molecules3,4.	SIGNOR-272339
P63000	Q92997	2	binding	up-regulates	0.467	Wnt/fz activation of rac and rho is inhibited by rac-n17 and rho-n19, respectively (figs. _(figs.1d,1d, _d,5c,d;5c,d;habas et al. 2001), and requires different dvl domains wnt signaling induces complex formation between dvl and rac.	SIGNOR-97409
P04150	Q13887	1	transcriptional regulation	up-regulates quantity by expression	0.292	We show that in addition, DEX-bound GR directly promotes the expression of adipogenic TFs, including C/EBPβ, Klf5, Klf9, and C/EBPα	SIGNOR-256118
Q6PHR2	Q6PHR2	2	phosphorylation	up-regulates activity	0.2	We show that ULK3 autophosphorylation occurs at four serine residues (Ser-300, Ser-350, Ser-384, and Ser-464) situated outside of the KD \| Thus, autophosphorylation of ULK3 may involve conformational changes resulted in exposure of CTD to KD and consequently in generation of the catalytically active kinase.	SIGNOR-260794
P17655	P49841	1	cleavage	up-regulates activity	0.285	Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase	SIGNOR-251613
P05129	P43629	1	phosphorylation	down-regulates	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.	SIGNOR-158133
P10275	Q00535	0	phosphorylation	up-regulates	0.371	Cdk5 enables phosphorylation of ar at ser-81 site through direct biochemical interaction and, therefore, results in the stabilization of ar proteins	SIGNOR-175696
P51114	Q13153	0	phosphorylation	up-regulates activity	0.271	Identification of Ser420 in FXR1 as a PAK1 Kinase Target. During zebrafish muscle development, FXR1 Ser420 phosphorylation is needed for protein function.	SIGNOR-273713
Q01860	Q96GD4	0	phosphorylation	down-regulates activity	0.38	Aurkb phosphorylates Oct4(S229) during G2/M phase, leading to the dissociation of Oct4 from chromatin, whereas PP1 binds Oct4 and dephosphorylates Oct4(S229) during M/G1 transition, which resets Oct4-driven transcription for pluripotency and the cell cycle.	SIGNOR-279592
Q14500	P17612	0	phosphorylation	down-regulates activity	0.283	Phosphorylation of the Kir2.2 C terminus by protein kinase A inhibited the association with SAP97.‚	SIGNOR-249998
P38646	P53602	2	binding	down-regulates activity	0.342	Mortalin binds to mevalonate pyrophosphate decarboxyl ase in mammalian cell. Mot-2 inactivates MPD resulting in decreased amounts of the steady state Ras protein.	SIGNOR-265890
Q4VCS5	P46937	1	relocalization	down-regulates	0.734	Yap/taz and angiomotin (amot) family proteins were shown to interact, resulting in yap/taz localization to tight junctions and inhibition through phosphorylation-dependent and -independent mechanisms.	SIGNOR-175779
P98170	O15294	1	ubiquitination	down-regulates quantity	0.2	These results demonstrate that XIAP acts as an E3 ubiquitin ligase and ubiquitinates OGT in HCT116 colon cancer cells.\|XIAP promotes the ubiquitin-dependent proteasomal degradation of OGT.	SIGNOR-278800
Q92831	P0DPK5	1	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-269615
Q99835	P48729	0	phosphorylation	up-regulates	0.521	We demonstrate that mammalian Smo (mSmo) is activated through multi-site phosphorylation of its carboxyl-terminal tail by CK1α and GRK2. Phosphorylation of mSmo induces its active conformation and simultaneously promotes its ciliary accumulation.	SIGNOR-174542
Q9UKA1	Q9BQ15	2	binding	down-regulates quantity by destabilization	0.344	Here, we report that hSSB1 is the bona fide substrate for an Fbxl5-containing SCF (Skp1-Cul1-F box) E3 ligase. Fbxl5 interacts with and targets hSSB1 for ubiquitination and degradation, which could be prevented by ATM-mediated hSSB1 T117 phosphorylation.	SIGNOR-271655
P01236	P16471	2	binding	up-regulates	0.924	Prolactin-dependent signaling occurs as the result of ligand-induced dimerization of the prolactin receptor (prlr).	SIGNOR-72810
Q5TG30	P61586	1	gtpase-activating protein	down-regulates activity	0.432	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-260496
P11362	Q8WU20	1	phosphorylation	up-regulates activity	0.867	As shown in xref , wild type FGFR1c phosphorylated FRS2\u03b1 on tyrosine 196 whereas the V429E mutant did not.	SIGNOR-280013
Q9NRD0	P62330	2	binding	down-regulates quantity by destabilization	0.71	Fbx8 Is a Component of the SCF Complex and Mediates Ubiquitination of Arf6. We first examined whether Fbx8 makes a complex with Cul1, through its binding to Skp1. We expressed GST-tagged Fbx8 together with FLAG-tagged Skp1 and Myc-tagged Cul1 in Cos-7 cells and found that Myc-Cul1 is coprecipitated with GST-Fbx8 in the presence of FLAG-Skp1 (Figure 1A).	SIGNOR-271764
Q96ME1	P19447	2	binding	down-regulates quantity by destabilization	0.2	These results led us to propose a model that spironolactone may trigger the phosphorylation of XPB at Ser90 by CDK7, which promotes the recognition and polyubiquitination of XPB by SCFFBXL18 for proteasomal degradation.	SIGNOR-277434
P06241	Q16236	1	phosphorylation	down-regulates quantity	0.4	Fyn phosphorylates Nrf2 Y568, resulting in nuclear export and degradation of Nrf2.\|Fyn phosphorylates Nrf2Y568 resulting in nuclear export and degradation of Nrf2.	SIGNOR-278358
Q9NR19	P04062	1	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
P48729	Q13501	1	phosphorylation	up-regulates activity	0.391	Mechanistically, CSNK1A1 interacted with STING1 upon the CGAS-STING1 pathway activation and promoted STING1 autophagic degradation by enhancing the phosphorylation of SQSTM1/p62 at serine 351 (serine 349 in human), which was critical for SQSTM1-mediated STING1 autophagic degradation.	SIGNOR-273769
P33076	P27361	0	phosphorylation	up-regulates	0.341	We found that in these cells, lipopolysaccharide stimulates the expression of mhc ii genes via the activation of erk1/2, which is mediated by toll-like receptor 4. Erk1/2 then phosphorylates the serine at position 357, which is located in a degron of ciita isoform 1 that leads to its monoubiquitylation.	SIGNOR-150545
P17252	O14986	1	phosphorylation	down-regulates	0.2	Collaboration of ampk and pkc to induce phosphorylation of ser413 on pip5k1b resulting in decreased kinase activity and reduced ptdins(4,5)p2 synthesis in response to oxidative stress and energy restriction. we demonstrate that pkc can directly phosphorylate ser413 in vitro	SIGNOR-194820
Q15596	P10276	2	binding	up-regulates	0.631	Transcriptional coactivator for steroid receptors and nuclear receptors.nteracts with casp8ap2 and ttll5/stamp. Interacts with esr1, rara and rxra.	SIGNOR-96827
O75385	Q96KB5	0	phosphorylation	down-regulates activity	0.2	We found that TOPK could directly bind with and phosphorylate ULK1 at Ser469, Ser495, and Ser533. The phosphorylation of ULK1 at Ser469, Ser495, and Ser533 by TOPK decreased the activity and stability of ULK1.	SIGNOR-277473
Q15848	Q96A54	2	binding	up-regulates	0.677	Two adiponectin receptors, adipor1 and adipor2, have recently been identified.	SIGNOR-146170
P49759	Q96I25	1	phosphorylation	up-regulates activity	0.317	In this work, we show that Cdc2-like kinase 1 (Clk1) phosphorylates SPF45 on eight serine residues.	SIGNOR-262710
P12931	Q9ULV8	1	phosphorylation	up-regulates	0.537	Phosphorylation of a critical tyrosine (tyr-341) in the linker region of cbl-c by src or a phosphomimetic mutation of this tyrosine (y341e) is sufficient to increase the e3 activity of cbl-c.	SIGNOR-165862
P61586	Q5T5U3	0	gtpase-activating protein	down-regulates activity	0.628	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-260475
Q14847	P12931	0	phosphorylation	up-regulates activity	0.253	Integrin-dependent translocation of LASP-1 to the cytoskeleton of activated platelets correlates with LASP-1 phosphorylation at tyrosine 171 by Src-kinase	SIGNOR-271706
O43683	Q13257	1	relocalization	up-regulates activity	0.96	Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity	SIGNOR-252018
O95837	P25105	2	binding	up-regulates activity	0.413	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-257436
P23470	O60496	1	dephosphorylation	up-regulates activity	0.2	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254698
P67775	Q70Z35	1	dephosphorylation	up-regulates activity	0.2	PREX2 is dephosphorylated by PP1α and PP2A.PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ.	SIGNOR-277184
Q9H7Z6	Q03164	2	binding	up-regulates	0.488	Mll1 and mof can form a stable complex in vivo / given that an interaction of dmof with msl1 through its zinc finger is essential for correct targeting of mof to the male x chromosome	SIGNOR-138245
Q07666	O15111	0	phosphorylation	up-regulates activity	0.2	Sam68 is phosphorylated by IKK\u03b1 in the nucleus.	SIGNOR-278439
O00555	P43146	0	null	up-regulates activity	0.2	DCC activation by a netrin-1 gradient creates a high-level [Ca2+]i gradient by triggering LCC activity and by stimulating the cAMP–PKA pathway, which further activates LCC in the plasma membrane (PM) and Ca2+ channels in the ER.	SIGNOR-268293
O76039	P49418	1	phosphorylation	down-regulates activity	0.36	This 120-kDa protein was identified as amphiphysin 1 (Amph1) by LC-MS/MS analysis, and the site of phosphorylation by CDKL5 was determined to be Ser-293.\| The phosphorylation mimic mutants, Amph1(S293E) and Amph1(S293D), showed significantly reduced affinity for endophilin, a protein involved in synaptic vesicle endocytosis	SIGNOR-245881
P45983	P05787	1	phosphorylation	up-regulates	0.375	Kinase assays showed that c-jun n-terminal kinase (jnk) was also activated with activation kinetics corresponding to that of k8 phosphorylation. Furthermore, k8 was also phosphorylated on ser-73 by jnk in vitro. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis.	SIGNOR-113645
P10721	P17252	0	phosphorylation	down-regulates	0.531	Phosphorylation of kit/scfr by pkc-_ in vitro: identification of ser-741 and ser-746 as the major phosphorylation sites for pkc / pkc, which acts in an scf-stimulated feedback loop, that negatively controls kit/scfr kinase activity	SIGNOR-28605
Q9Y239	Q676U5	2	binding	up-regulates activity	0.681	By a mechanism independent of the adaptor RIP2 and transcription factor NF-kappaB, Nod1 and Nod2 recruited the autophagy protein ATG16L1 to the plasma membrane at the bacterial entry site. Our results link bacterial sensing by Nod proteins to the induction of autophagy and provide a functional link between Nod2 and ATG16L1, which are encoded by two of the most important genes associated with Crohn's disease.	SIGNOR-252406
P32754	A6NLP5	2	binding	up-regulates quantity by stabilization	0.27	Decreased expression of 4-hydroxyphenylpyruvic acid dioxygenase (HPD), a key enzyme for tyrosine metabolism, is a cause of human tyrosinemia. However, the regulation of HPD expression remains largely unknown. Here, we demonstrate that molecular chaperone TTC36, which is highly expressed in liver, is associated with HPD and reduces the binding of protein kinase STK33 to HPD, thereby inhibiting STK33-mediated HPD T382 phosphorylation. The reduction of HPD T382 phosphorylation results in impaired recruitment of FHA domain-containing PELI1 and PELI1-mediated HPD polyubiquitylation and degradation.	SIGNOR-272960
P40763	P07948	0	phosphorylation	up-regulates activity	0.659	An in vitro phosphorylation assay showed that Lyn directly phosphorylates STAT3.	SIGNOR-279062
Q9UKT7	Q49AN0	2	binding	down-regulates quantity by destabilization	0.769	We found that both Cry1 and Cry2 proteins are ubiquitinated and degraded via the SCF(Fbxl3) ubiquitin ligase complex. This regulation by SCF(Fbxl3) is a prerequisite for the efficient and timely reactivation of Clock-Bmal1 and the consequent expression of Per1 and Per2, two regulators of the circadian clock that display tumor suppressor activity. HEK293T cells were transfected with Cry2, Skp1, Cul1, and Roc1 in the absence or presence of either FLAG-tagged Fbxl3 or a FLAG-tagged Fbxl3(ΔF-box) mutant. Fbxl3, but not an inactive Fbxl3(ΔF-box) mutant (4), induced the ubiquitination of Cry2 (Fig. 2D), which supports the notion that the effect of Fbxl3 on Cry2 is direct.	SIGNOR-271648
P46527	P49336	0	phosphorylation	down-regulates	0.289	As a consequence, CDK8 overexpression promoted p27 degradation, whereas CDK8 knockdown reduced it.\|We also show that CDK8 promotes phosphorylation of p27 at T187 and then induces p27 ubiquitination and degradation in a Skp2-dependent manner.	SIGNOR-278513
P01137	Q14766	2	binding	up-regulates activity	0.638	Together these data form strong support for the hypothesis that the LTBP plays an essential role in the activation of latent TGF-b in heterotypic cultures.	SIGNOR-235754
P12931	P49279	1	phosphorylation	up-regulates activity	0.281	In this study, we provide evidence that SLC11A1 is phosphorylated by Src family kinases at tyrosine 15 present in a conserved tyrosine-based motif (YGSI) among all species.	SIGNOR-278500
P04637	P34947	0	phosphorylation	down-regulates	0.37	Grk5, but not grk2 or grk6, phosphorylates p53 at thr-55, which promotes the degradation of p53, leading to inhibition of p53-dependent apoptotic response to genotoxic damage.	SIGNOR-163707
P37840	P00519	0	phosphorylation	up-regulates quantity	0.424	C-Abl interacts with alpha-synuclein and phosphorylates alpha-synuclein at Y39 (XREF_FIG) .	SIGNOR-279582
Q93008	O60729	0	dephosphorylation	down-regulates quantity by destabilization	0.2	Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis.	SIGNOR-275613
Q5S007	Q5S007	2	phosphorylation	up-regulates	0.2	Three putative autophosphorylation sites (thr-2031, ser-2032, and thr-2035) have been identified within the activation segment of the lrrk2 kinase domain based on sequence homology to mixed-lineage kinases. Phosphorylation at one or more of these sites is critical for the kinase activity of lrrk2.	SIGNOR-166470
O60674	Q15910	1	phosphorylation	down-regulates	0.534	Oncogenic y641 mutations in ezh2 prevent jak2/beta-trcp-mediated degradationbeta-trcp ubiquitinates ezh2 and jak2-mediated phosphorylation on y641 directs beta-trcp-mediated ezh2 degradation.	SIGNOR-202711
P29474	P22612	0	phosphorylation	up-regulates	0.2	Recently many investigators have shown that protein phosphorylation of enos by several serine/threonine kinases is a critical control step for no production by endothelial cells. Phosphorylation by amp kinase, akt (or protein kinase b), or protein kinase a on serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no.	SIGNOR-112375
P17544	O00268	2	binding	down-regulates activity	0.397	These results not only demonstrate an interaction between ATF7 and TAF4 but also indicate, as in the case of TAF12 (see Figure 3e), that no additional cellular component is required for this binding. They also suggest that TAF4 may interfere with the formation of ATF7TAF12 subcomplexes, thereby inhibiting ATF7-induced transactivation.	SIGNOR-225300
P49841	Q5JTC6	0	relocalization	up-regulates activity	0.419	Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.	SIGNOR-171892
Q9NY65	Q5SQI0	0	acetylation	up-regulates quantity by stabilization	0.244	Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.\|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules	SIGNOR-272250
Q13555	P42261	1	phosphorylation	up-regulates activity	0.63	In this study, CaM-kinase II enhanced kainate currents of expressed glutamate receptor 6 in 293 cells and of wild-type glutamate receptor 1, but not the Ser-627 to Ala mutant, in Xenopus oocytes. \| This CaM-kinase II regulatory phosphorylation site is conserved in all AMPA/kainate-type glutamate receptors, and its phosphorylation may be important in enhancing postsynaptic responsiveness as occurs during synaptic plasticity.	SIGNOR-250697
Q14156	P01116	2	binding	up-regulates quantity	0.2	EFR3A directly binds to active KRAS through its C-terminus. EFR3A promotes the localization and nanoclustering of KRAS at the plasma membrane.	SIGNOR-269094
Q8WZ74	Q9BYB0	2	binding	up-regulates activity	0.2	Synaptopathy, a key feature of autism spectrum disorders (ASD), is likely relevant to the impaired phase separation and/or transition of ASD-linked synaptic proteins. Here, we report that LLPS and zinc-induced liquid-to-gel phase transition regulate the synaptic distribution and protein-protein interaction of cortactin-binding protein 2 (CTTNBP2), an ASD-linked protein. CTTNBP2 forms self-assembled condensates through its C-terminal intrinsically disordered region and facilitates SHANK3 co-condensation at dendritic spines.	SIGNOR-269702
Q96HN2	P51003	2	binding	down-regulates activity	0.2	Inositol 1,4,5-triphosphate receptor-binding protein released with inositol 1,4,5-triphosphate (IRBIT) associates with components of the mRNA 3' processing machinery in a phosphorylation-dependent manner and inhibits polyadenylation\|In addition to CPSF, IRBIT interacted in vitro with poly(A) polymerase (PAP), which is the enzyme recruited by CPSF to elongate the poly(A) tail, and inhibited PAP activity in a phosphorylation-dependent manner.	SIGNOR-268330
Q13049	P01106	1	ubiquitination	down-regulates quantity by destabilization	0.456	TRIM32 ubiquitinates and degrades the transcription factor c-Myc but also binds Argonaute-1 and thereby increases the activity of specific microRNAs.	SIGNOR-278676
P46734	Q99759	0	phosphorylation	up-regulates activity	0.558	These data indicate that mkk3 is preferentially activated by mekk3, whereas mkk4 is activated both by mekk2 and mekk3.	SIGNOR-48625
O95837	P20309	2	binding	up-regulates activity	0.411	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-257134
O43462	Q96BA8	1	cleavage	up-regulates	0.568	Cleavage of oasis by site-1 and site-2 proteases / oasis is cleaved at the membrane under er stress conditions and that its cleaved n-terminal domain translocates into the nucleus;and then activates transcription of target genes	SIGNOR-143820
Q8N6T7	P36956	2	binding	up-regulates activity	0.371	SIRT6 directs chromatin recruitment of CLOCK:BMAL1 and SREBP1.Importantly, SIRT6 also controls SREBP-1 recruitment to target promoters, such as Fasn, and helps maintain proper cyclic transcription. In fact, circadian metabolomics analyses reveal that SIRT6 controls lipid metabolism, contributing to the regulation of pathways involved in fatty acid synthesis and beta oxidation, triglyceride storage, signaling, and cellular membrane lipids.	SIGNOR-268158
P21860	P00533	0	phosphorylation	up-regulates	0.67	The erbb3 protein which possesses little or no intrinsic protein tyrosine kinase activiity is phosphorylated by the activated egf receptor protein tyrosine kinase on tyrosine residues within the yxxm sequence motif. These phosphorylated tyrosine residues interact with the p85 regulatory subunit of pi 3-kinase, which could result in the activation of the p110 catalytic subunit via a conformational mechanism.	SIGNOR-34748
Q9H4B4	Q14790	1	phosphorylation	up-regulates activity	0.338	Furthermore, we identify caspase-8 as a new substrate for Plk3. Phosphorylation occurs on T273 and results in stimulation of caspase-8 proapoptotic function.	SIGNOR-272995
Q13976	Q13507-3	1	phosphorylation	down-regulates	0.408	The present study demonstrates that human trpc3 expressed in hek293 cells forms store-operated ca2+ influx channels, the activity of which is inhibited by pkg. The inhibition is due to a direct phosphorylation of pkg on trpc3 channels at position t11 and s263.	SIGNOR-142957
O00141	P46527	1	phosphorylation	down-regulates	0.469	Activated sgk1 and p27 phosphorylation at t157, and both were inhibited by short-term rapamycin treatment and by sgk1 shrna.	SIGNOR-179117
P55283	P07737	0	null	up-regulates activity	0.335	Taken together, data obtained from MCF10A cells were consistent with the idea that Rho signaling to Dia1 and profilin-1 was essential for R-cadherin adherens junction formation.	SIGNOR-253111
P53667	P23470	0	dephosphorylation	down-regulates activity	0.26	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254711
O94916	Q8N752	0	phosphorylation	up-regulates activity	0.2	However, the siRNA knockdown of CK1α1L significantly reduced the nuclear export of OREBP/TonEBP under hypotonic conditions (Fig. 5F). Taken together, these data suggest that CK1α1L is the kinase that phosphorylates Ser-158 in the regulation of OREBP/TonEBP export.	SIGNOR-274111
Q13614	O95248	2	binding	up-regulates activity	0.635	We also demonstrate that MTMR2 interacts with MTMR5 via its coiled-coil domain and that mutations in the coiled-coil domain of either MTMR2 or MTMR5 abrogate this interaction. Through this interaction, MTMR5 increases the enzymatic activity of MTMR2 and dictates its subcellular localization.	SIGNOR-269803
Q9H171	Q9Y572	2	binding	up-regulates activity	0.637	ZBP1 initiates RIPK3-driven cell death by sensing IAV RNA and activating RIPK3. Here, we show that replicating IAV generates Z-RNAs, which activate ZBP1 in the nucleus of infected cells. ZBP1 then initiates RIPK3-mediated MLKL activation in the nucleus, resulting in nuclear envelope disruption, leakage of DNA into the cytosol, and eventual necroptosis.	SIGNOR-266430
P63092	P43088	2	binding	up-regulates activity	0.373	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚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-256810
Q02086	P10914	2	binding	up-regulates activity	0.339	Sp2 could be also able to interact with IRF-1 and this interaction is also observed on DNA indicating that by this way Sp2 is able to modulate IRF-1 transcriptional activity.	SIGNOR-226478
Q15835	Q13009	1	phosphorylation	down-regulates activity	0.2	For example, RhoK phosphorylates and inhibits TIAM1, STEF, and PAR3; disrupts the polarity complex; and prevents Rac activation ( xref ).	SIGNOR-279995
Q16539	P13726	1	phosphorylation	down-regulates	0.291	We previously showed that the phosphorylation of ser253 within the cytoplasmic domain of human tissue factor (tf) initiates the incorporation and release of this protein into cell-derived microparticles. Furthermore, subsequent phosphorylation of ser258 terminates this process. Our current study has identified p38_ as a major kinase, responsible for the phosphorylation of ser258 within the cytoplasmic domain of tf	SIGNOR-199868
P31943	Q9UKA9	2	binding	up-regulates activity	0.389	Splicing of the c-src N1 exon in neuronal cells depends in part on an intronic cluster of RNA regulatory elements called the downstream control sequence (DCS). \|nPTB binds more stably to the DCS RNA than PTB does but is a weaker repressor of splicing in vitro. nPTB also greatly enhances the binding of two other proteins, hnRNP H and KSRP, to the DCS RNA.	SIGNOR-261269

O95817

Q00535

0

phosphorylation

down-regulates quantity by destabilization

0.2

CDK5-mediated phosphorylation on S297 promotes BAG3 degradation.

SIGNOR-277502

P17252

Q86UR1

1

phosphorylation

down-regulates

0.29

Phosphorylation of nadph oxidase activator 1 (noxa1) on serine 282 by map kinases and on serine 172 by protein kinase c and protein kinase a prevents nox1 hyperactivation.

SIGNOR-163667

P30260

P06493

0

phosphorylation

up-regulates

0.704

Apc activation is thought to depend on apc phosphorylation and cdc20 binding. We have identified 43 phospho_sites on apc of which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts of apc1 and the tetratricopeptide repeat (tpr) subunits cdc27, cdc16, cdc23 and apc7. In vitro, at least 15 of the mitotic phospho_sites can be generated by cyclin_dependent kinase 1 (cdk1), and 3 by polo_like kinase 1 (plk1). Apc phosphorylation by cdk1, but not by plk1, is sufficient for increased cdc20 binding and apc activation

SIGNOR-119873

P04637

Q93009

0

deubiquitination

up-regulates

0.741

Hausp counteracts the destabilizing effect of mdm2 by direct deubiquitination of p53.

SIGNOR-139456

P23468

P40763

1

dephosphorylation

down-regulates activity

0.517

Transfection of wild-type PTPRD resulted in the specific dephosphorylation of STAT3 at tyrosine 705, a residue that must be phosphorylated for STAT3 to be active

SIGNOR-248442

O60229

Q8IW41

0

phosphorylation

up-regulates activity

0.385

The brain-specific nucleotide exchange factor kalirin-7 (Kal7) was identified as an MK5 interaction partner and substrate protein. The MK5 substrate Kal7, a Rho GEF and known activator of Rac GTPases, further contributes to PAK activation and actin filament reorganization. Thus, the coordinated phosphorylation of Borg proteins and Kal7 by ERK3 and MK5 constitute a novel signaling cascade involving feed-forward circuits, multiple GTPases, and cytoskeletal elements. The fragment SR3-6, but not the mutated fragment SR3-6-S487A, is phosphorylated by MK5.

SIGNOR-263093

P24723

P09211

1

phosphorylation

up-regulates activity

0.2

Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently

SIGNOR-276014

O95837

Q99677

2

binding

up-regulates activity

0.385

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-257432

P29317

P52797

2

binding

up-regulates

0.814

The eph family of receptors.

SIGNOR-52309

O95600

Q13351

0

transcriptional regulation

up-regulates quantity by expression

0.25

Here we report that Klf8 is repressed by Klf3 in vivo and is up-regulated by Klf1. Transcript analysis indicates that Klf8 has two promoters, both containing multiple CACCC elements. Transactivation assays and chromatin immunoprecipitation experiments indicate that Klf3 represses Klf8 directly and that Klf1 activates Klf8 directly.

SIGNOR-266050

Q15788

P27361

0

phosphorylation

up-regulates

0.268

Mapk also directly phosphorylates src-1 at thr1179 and ser1185. Phosphorylation of src-1 by mitogen-activated protein kinase (mapk) is required for optimal progesterone receptor-dependent transcription and for functional cooperation with camp response element-binding protein-binding protein

SIGNOR-91143

P10275

Q07912

0

phosphorylation

up-regulates activity

0.545

Ack1 interacted with and phosphorylated AR protein at Tyr 267 and Ack1 was shown to be required for optimal AR target gene expression and AR recruitment.|Two intracellular tyrosine kinases, Ack1 (activated cdc42 associated kinase) and Src, phosphorylate and enhance AR activity and promote prostate xenograft tumor growth in castrated animals.

SIGNOR-278194

P23468

Q96NI6

2

binding

up-regulates activity

0.277

SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development. we identified LAR-RPTPs as novel ligands of SALM5 that mediates SALM5-dependent presynaptic differentiation in a splicing-dependent manner. Our data indicate that SALM5 interacts with all three known LAR-RPTPs—LAR, PTPδ, and PTPσ (Fig. 1).

SIGNOR-264086

Q9ULA0

Q13107

1

cleavage

down-regulates quantity by destabilization

0.2

A further analysis showed that the hydrolysis pathway contributes to DNPEP-mediated degradation of USP4 (Supporting Information Figs. S3A–S3F). The interaction between USP4 and DNPEP was confirmed by coIP assays

SIGNOR-275652

P06744

P68400

0

phosphorylation

down-regulates activity

0.333

It is known that human PGI/AMF is phosphorylated at Ser(185) by protein kinase CK2 (CK2) | These results demonstrate that phosphorylation affects the allosteric kinetic properties of the enzyme, resulting in a less active form of PGI, whereas non-phosphorylated protein species retain cytokine activity.

SIGNOR-250869

O14654

Q8WYL5

2

binding

up-regulates activity

0.311

Insulin Receptor Substrate-4 Binds to Slingshot-1 Phosphatase and Promotes Cofilin Dephosphorylation. In addition, IRS4 co-localized with SSH1 in F-actin-rich membrane protrusions in insulin-stimulated cells, which suggests that the association of IRS4 with SSH1 contributes to localized activation of cofilin in membrane protrusions.

SIGNOR-277617

P31751

P49841

1

phosphorylation

down-regulates activity

0.623

Active AKT, a common mediator of cell survival signals induced by radiation through multiple intracellular signaling pathways,11, 12 suppresses apoptosis. AKT positively regulates cyclin D1 expression through inactivation of glycogen synthase kinase 3_ (GSK3_). The AKT-mediated phosphorylation of glycogen synthase kinase 3_ on serine9 decreases its kinase activity for Thr286 of cyclin D1, which inhibits the nuclear export and the cytoplasmic proteasomal degradation of cyclin D1

SIGNOR-245420

P15923

P49137

0

phosphorylation

up-regulates

0.52

Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2

SIGNOR-166643

P02461

P03956

0

cleavage

down-regulates quantity by destabilization

0.35

In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775–Ile776 or Gly775–Lys776 in native type I, II or III collagen molecules3,4.

SIGNOR-272339

P63000

Q92997

2

binding

up-regulates

0.467

Wnt/fz activation of rac and rho is inhibited by rac-n17 and rho-n19, respectively (figs. _(figs.1d,1d, _d,5c,d;5c,d;habas et al. 2001), and requires different dvl domains wnt signaling induces complex formation between dvl and rac.

SIGNOR-97409

P04150

Q13887

1

transcriptional regulation

up-regulates quantity by expression

0.292

We show that in addition, DEX-bound GR directly promotes the expression of adipogenic TFs, including C/EBPβ, Klf5, Klf9, and C/EBPα

SIGNOR-256118

Q6PHR2

2

phosphorylation

up-regulates activity

0.2

We show that ULK3 autophosphorylation occurs at four serine residues (Ser-300, Ser-350, Ser-384, and Ser-464) situated outside of the KD | Thus, autophosphorylation of ULK3 may involve conformational changes resulted in exposure of CTD to KD and consequently in generation of the catalytically active kinase.

SIGNOR-260794

P17655

P49841

1

cleavage

up-regulates activity

0.285

Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase

SIGNOR-251613

P05129

P43629

1

phosphorylation

down-regulates

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.

SIGNOR-158133

P10275

Q00535

0

phosphorylation

up-regulates

0.371

Cdk5 enables phosphorylation of ar at ser-81 site through direct biochemical interaction and, therefore, results in the stabilization of ar proteins

SIGNOR-175696

P51114

Q13153

0

phosphorylation

up-regulates activity

0.271

Identification of Ser420 in FXR1 as a PAK1 Kinase Target. During zebrafish muscle development, FXR1 Ser420 phosphorylation is needed for protein function.

SIGNOR-273713

Q01860

Q96GD4

0

phosphorylation

down-regulates activity

0.38

Aurkb phosphorylates Oct4(S229) during G2/M phase, leading to the dissociation of Oct4 from chromatin, whereas PP1 binds Oct4 and dephosphorylates Oct4(S229) during M/G1 transition, which resets Oct4-driven transcription for pluripotency and the cell cycle.

SIGNOR-279592

Q14500

P17612

0

phosphorylation

down-regulates activity

0.283

Phosphorylation of the Kir2.2 C terminus by protein kinase A inhibited the association with SAP97.‚

SIGNOR-249998

P38646

P53602

2

binding

down-regulates activity

0.342

Mortalin binds to mevalonate pyrophosphate decarboxyl ase in mammalian cell. Mot-2 inactivates MPD resulting in decreased amounts of the steady state Ras protein.

SIGNOR-265890

Q4VCS5

P46937

1

relocalization

down-regulates

0.734

Yap/taz and angiomotin (amot) family proteins were shown to interact, resulting in yap/taz localization to tight junctions and inhibition through phosphorylation-dependent and -independent mechanisms.

SIGNOR-175779

P98170

O15294

1

ubiquitination

down-regulates quantity

0.2

These results demonstrate that XIAP acts as an E3 ubiquitin ligase and ubiquitinates OGT in HCT116 colon cancer cells.|XIAP promotes the ubiquitin-dependent proteasomal degradation of OGT.

SIGNOR-278800

Q92831

P0DPK5

1

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-269615

Q99835

P48729

0

phosphorylation

up-regulates

0.521

We demonstrate that mammalian Smo (mSmo) is activated through multi-site phosphorylation of its carboxyl-terminal tail by CK1α and GRK2. Phosphorylation of mSmo induces its active conformation and simultaneously promotes its ciliary accumulation.

SIGNOR-174542

Q9UKA1

Q9BQ15

2

binding

down-regulates quantity by destabilization

0.344

Here, we report that hSSB1 is the bona fide substrate for an Fbxl5-containing SCF (Skp1-Cul1-F box) E3 ligase. Fbxl5 interacts with and targets hSSB1 for ubiquitination and degradation, which could be prevented by ATM-mediated hSSB1 T117 phosphorylation.

SIGNOR-271655

P01236

P16471

2

binding

up-regulates

0.924

Prolactin-dependent signaling occurs as the result of ligand-induced dimerization of the prolactin receptor (prlr).

SIGNOR-72810

Q5TG30

P61586

1

gtpase-activating protein

down-regulates activity

0.432

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-260496

P11362

Q8WU20

1

phosphorylation

up-regulates activity

0.867

As shown in xref , wild type FGFR1c phosphorylated FRS2\u03b1 on tyrosine 196 whereas the V429E mutant did not.

SIGNOR-280013

Q9NRD0

P62330

2

binding

down-regulates quantity by destabilization

0.71

Fbx8 Is a Component of the SCF Complex and Mediates Ubiquitination of Arf6. We first examined whether Fbx8 makes a complex with Cul1, through its binding to Skp1. We expressed GST-tagged Fbx8 together with FLAG-tagged Skp1 and Myc-tagged Cul1 in Cos-7 cells and found that Myc-Cul1 is coprecipitated with GST-Fbx8 in the presence of FLAG-Skp1 (Figure 1A).

SIGNOR-271764

Q96ME1

P19447

2

binding

down-regulates quantity by destabilization

0.2

These results led us to propose a model that spironolactone may trigger the phosphorylation of XPB at Ser90 by CDK7, which promotes the recognition and polyubiquitination of XPB by SCFFBXL18 for proteasomal degradation.

SIGNOR-277434

P06241

Q16236

1

phosphorylation

down-regulates quantity

0.4

Fyn phosphorylates Nrf2 Y568, resulting in nuclear export and degradation of Nrf2.|Fyn phosphorylates Nrf2Y568 resulting in nuclear export and degradation of Nrf2.

SIGNOR-278358

Q9NR19

P04062

1

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

P48729

Q13501

1

phosphorylation

up-regulates activity

0.391

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

SIGNOR-273769

P33076

P27361

0

phosphorylation

up-regulates

0.341

We found that in these cells, lipopolysaccharide stimulates the expression of mhc ii genes via the activation of erk1/2, which is mediated by toll-like receptor 4. Erk1/2 then phosphorylates the serine at position 357, which is located in a degron of ciita isoform 1 that leads to its monoubiquitylation.

SIGNOR-150545

P17252

O14986

1

phosphorylation

down-regulates

0.2

Collaboration of ampk and pkc to induce phosphorylation of ser413 on pip5k1b resulting in decreased kinase activity and reduced ptdins(4,5)p2 synthesis in response to oxidative stress and energy restriction. we demonstrate that pkc can directly phosphorylate ser413 in vitro

SIGNOR-194820

Q15596

P10276

2

binding

up-regulates

0.631

Transcriptional coactivator for steroid receptors and nuclear receptors.nteracts with casp8ap2 and ttll5/stamp. Interacts with esr1, rara and rxra.

SIGNOR-96827

O75385

Q96KB5

0

phosphorylation

down-regulates activity

0.2

We found that TOPK could directly bind with and phosphorylate ULK1 at Ser469, Ser495, and Ser533. The phosphorylation of ULK1 at Ser469, Ser495, and Ser533 by TOPK decreased the activity and stability of ULK1.

SIGNOR-277473

Q15848

Q96A54

2

binding

up-regulates

0.677

Two adiponectin receptors, adipor1 and adipor2, have recently been identified.

SIGNOR-146170

P49759

Q96I25

1

phosphorylation

up-regulates activity

0.317

In this work, we show that Cdc2-like kinase 1 (Clk1) phosphorylates SPF45 on eight serine residues.

SIGNOR-262710

P12931

Q9ULV8

1

phosphorylation

up-regulates

0.537

Phosphorylation of a critical tyrosine (tyr-341) in the linker region of cbl-c by src or a phosphomimetic mutation of this tyrosine (y341e) is sufficient to increase the e3 activity of cbl-c.

SIGNOR-165862

P61586

Q5T5U3

0

gtpase-activating protein

down-regulates activity

0.628

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-260475

Q14847

P12931

0

phosphorylation

up-regulates activity

0.253

Integrin-dependent translocation of LASP-1 to the cytoskeleton of activated platelets correlates with LASP-1 phosphorylation at tyrosine 171 by Src-kinase

SIGNOR-271706

O43683

Q13257

1

relocalization

up-regulates activity

0.96

Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity

SIGNOR-252018

O95837

P25105

2

binding

up-regulates activity

0.413

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-257436

P23470

O60496

1

dephosphorylation

up-regulates activity

0.2

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254698

P67775

Q70Z35

1

dephosphorylation

up-regulates activity

0.2

PREX2 is dephosphorylated by PP1α and PP2A.PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ.

SIGNOR-277184

Q9H7Z6

Q03164

2

binding

up-regulates

0.488

Mll1 and mof can form a stable complex in vivo / given that an interaction of dmof with msl1 through its zinc finger is essential for correct targeting of mof to the male x chromosome

SIGNOR-138245

Q07666

O15111

0

phosphorylation

up-regulates activity

0.2

Sam68 is phosphorylated by IKK\u03b1 in the nucleus.

SIGNOR-278439

O00555

P43146

0

null

up-regulates activity

0.2

DCC activation by a netrin-1 gradient creates a high-level [Ca2+]i gradient by triggering LCC activity and by stimulating the cAMP–PKA pathway, which further activates LCC in the plasma membrane (PM) and Ca2+ channels in the ER.

SIGNOR-268293

O76039

P49418

1

phosphorylation

down-regulates activity

0.36

This 120-kDa protein was identified as amphiphysin 1 (Amph1) by LC-MS/MS analysis, and the site of phosphorylation by CDKL5 was determined to be Ser-293.| The phosphorylation mimic mutants, Amph1(S293E) and Amph1(S293D), showed significantly reduced affinity for endophilin, a protein involved in synaptic vesicle endocytosis

SIGNOR-245881

P45983

P05787

1

phosphorylation

up-regulates

0.375

Kinase assays showed that c-jun n-terminal kinase (jnk) was also activated with activation kinetics corresponding to that of k8 phosphorylation. Furthermore, k8 was also phosphorylated on ser-73 by jnk in vitro. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis.

SIGNOR-113645

P10721

P17252

0

phosphorylation

down-regulates

0.531

Phosphorylation of kit/scfr by pkc-_ in vitro: identification of ser-741 and ser-746 as the major phosphorylation sites for pkc / pkc, which acts in an scf-stimulated feedback loop, that negatively controls kit/scfr kinase activity

SIGNOR-28605

Q9Y239

Q676U5

2

binding

up-regulates activity

0.681

By a mechanism independent of the adaptor RIP2 and transcription factor NF-kappaB, Nod1 and Nod2 recruited the autophagy protein ATG16L1 to the plasma membrane at the bacterial entry site. Our results link bacterial sensing by Nod proteins to the induction of autophagy and provide a functional link between Nod2 and ATG16L1, which are encoded by two of the most important genes associated with Crohn's disease.

SIGNOR-252406

P32754

A6NLP5

2

binding

up-regulates quantity by stabilization

0.27

Decreased expression of 4-hydroxyphenylpyruvic acid dioxygenase (HPD), a key enzyme for tyrosine metabolism, is a cause of human tyrosinemia. However, the regulation of HPD expression remains largely unknown. Here, we demonstrate that molecular chaperone TTC36, which is highly expressed in liver, is associated with HPD and reduces the binding of protein kinase STK33 to HPD, thereby inhibiting STK33-mediated HPD T382 phosphorylation. The reduction of HPD T382 phosphorylation results in impaired recruitment of FHA domain-containing PELI1 and PELI1-mediated HPD polyubiquitylation and degradation.

SIGNOR-272960

P40763

P07948

0

phosphorylation

up-regulates activity

0.659

An in vitro phosphorylation assay showed that Lyn directly phosphorylates STAT3.

SIGNOR-279062

Q9UKT7

Q49AN0

2

binding

down-regulates quantity by destabilization

0.769

We found that both Cry1 and Cry2 proteins are ubiquitinated and degraded via the SCF(Fbxl3) ubiquitin ligase complex. This regulation by SCF(Fbxl3) is a prerequisite for the efficient and timely reactivation of Clock-Bmal1 and the consequent expression of Per1 and Per2, two regulators of the circadian clock that display tumor suppressor activity. HEK293T cells were transfected with Cry2, Skp1, Cul1, and Roc1 in the absence or presence of either FLAG-tagged Fbxl3 or a FLAG-tagged Fbxl3(ΔF-box) mutant. Fbxl3, but not an inactive Fbxl3(ΔF-box) mutant (4), induced the ubiquitination of Cry2 (Fig. 2D), which supports the notion that the effect of Fbxl3 on Cry2 is direct.

SIGNOR-271648

P46527

P49336

0

phosphorylation

down-regulates

0.289

As a consequence, CDK8 overexpression promoted p27 degradation, whereas CDK8 knockdown reduced it.|We also show that CDK8 promotes phosphorylation of p27 at T187 and then induces p27 ubiquitination and degradation in a Skp2-dependent manner.

SIGNOR-278513

P01137

Q14766

2

binding

up-regulates activity

0.638

Together these data form strong support for the hypothesis that the LTBP plays an essential role in the activation of latent TGF-b in heterotypic cultures.

SIGNOR-235754

P12931

P49279

1

phosphorylation

up-regulates activity

0.281

In this study, we provide evidence that SLC11A1 is phosphorylated by Src family kinases at tyrosine 15 present in a conserved tyrosine-based motif (YGSI) among all species.

SIGNOR-278500

P04637

P34947

0

phosphorylation

down-regulates

0.37

Grk5, but not grk2 or grk6, phosphorylates p53 at thr-55, which promotes the degradation of p53, leading to inhibition of p53-dependent apoptotic response to genotoxic damage.

SIGNOR-163707

P37840

P00519

0

phosphorylation

up-regulates quantity

0.424

C-Abl interacts with alpha-synuclein and phosphorylates alpha-synuclein at Y39 (XREF_FIG) .

SIGNOR-279582

Q93008

O60729

0

dephosphorylation

down-regulates quantity by destabilization

0.2

Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis.

SIGNOR-275613

Q5S007

2

phosphorylation

up-regulates

0.2

Three putative autophosphorylation sites (thr-2031, ser-2032, and thr-2035) have been identified within the activation segment of the lrrk2 kinase domain based on sequence homology to mixed-lineage kinases. Phosphorylation at one or more of these sites is critical for the kinase activity of lrrk2.

SIGNOR-166470

O60674

Q15910

1

phosphorylation

down-regulates

0.534

Oncogenic y641 mutations in ezh2 prevent jak2/beta-trcp-mediated degradationbeta-trcp ubiquitinates ezh2 and jak2-mediated phosphorylation on y641 directs beta-trcp-mediated ezh2 degradation.

SIGNOR-202711

P29474

P22612

0

phosphorylation

up-regulates

0.2

Recently many investigators have shown that protein phosphorylation of enos by several serine/threonine kinases is a critical control step for no production by endothelial cells. Phosphorylation by amp kinase, akt (or protein kinase b), or protein kinase a on serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no.

SIGNOR-112375

P17544

O00268

2

binding

down-regulates activity

0.397

These results not only demonstrate an interaction between ATF7 and TAF4 but also indicate, as in the case of TAF12 (see Figure 3e), that no additional cellular component is required for this binding. They also suggest that TAF4 may interfere with the formation of ATF7TAF12 subcomplexes, thereby inhibiting ATF7-induced transactivation.

SIGNOR-225300

P49841

Q5JTC6

0

relocalization

up-regulates activity

0.419

Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.

SIGNOR-171892

Q9NY65

Q5SQI0

0

acetylation

up-regulates quantity by stabilization

0.244

Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules

SIGNOR-272250

Q13555

P42261

1

phosphorylation

up-regulates activity

0.63

In this study, CaM-kinase II enhanced kainate currents of expressed glutamate receptor 6 in 293 cells and of wild-type glutamate receptor 1, but not the Ser-627 to Ala mutant, in Xenopus oocytes. | This CaM-kinase II regulatory phosphorylation site is conserved in all AMPA/kainate-type glutamate receptors, and its phosphorylation may be important in enhancing postsynaptic responsiveness as occurs during synaptic plasticity.

SIGNOR-250697

Q14156

P01116

2

binding

up-regulates quantity

0.2

EFR3A directly binds to active KRAS through its C-terminus. EFR3A promotes the localization and nanoclustering of KRAS at the plasma membrane.

SIGNOR-269094

Q8WZ74

Q9BYB0

2

binding

up-regulates activity

0.2

Synaptopathy, a key feature of autism spectrum disorders (ASD), is likely relevant to the impaired phase separation and/or transition of ASD-linked synaptic proteins. Here, we report that LLPS and zinc-induced liquid-to-gel phase transition regulate the synaptic distribution and protein-protein interaction of cortactin-binding protein 2 (CTTNBP2), an ASD-linked protein. CTTNBP2 forms self-assembled condensates through its C-terminal intrinsically disordered region and facilitates SHANK3 co-condensation at dendritic spines.

SIGNOR-269702

Q96HN2

P51003

2

binding

down-regulates activity

0.2

Inositol 1,4,5-triphosphate receptor-binding protein released with inositol 1,4,5-triphosphate (IRBIT) associates with components of the mRNA 3' processing machinery in a phosphorylation-dependent manner and inhibits polyadenylation|In addition to CPSF, IRBIT interacted in vitro with poly(A) polymerase (PAP), which is the enzyme recruited by CPSF to elongate the poly(A) tail, and inhibited PAP activity in a phosphorylation-dependent manner.

SIGNOR-268330

Q13049

P01106

1

ubiquitination

down-regulates quantity by destabilization

0.456

TRIM32 ubiquitinates and degrades the transcription factor c-Myc but also binds Argonaute-1 and thereby increases the activity of specific microRNAs.

SIGNOR-278676

P46734

Q99759

0

phosphorylation

up-regulates activity

0.558

These data indicate that mkk3 is preferentially activated by mekk3, whereas mkk4 is activated both by mekk2 and mekk3.

SIGNOR-48625

O95837

P20309

2

binding

up-regulates activity

0.411

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-257134

O43462

Q96BA8

1

cleavage

up-regulates

0.568

Cleavage of oasis by site-1 and site-2 proteases / oasis is cleaved at the membrane under er stress conditions and that its cleaved n-terminal domain translocates into the nucleus;and then activates transcription of target genes

SIGNOR-143820

Q8N6T7

P36956

2

binding

up-regulates activity

0.371

SIRT6 directs chromatin recruitment of CLOCK:BMAL1 and SREBP1.Importantly, SIRT6 also controls SREBP-1 recruitment to target promoters, such as Fasn, and helps maintain proper cyclic transcription. In fact, circadian metabolomics analyses reveal that SIRT6 controls lipid metabolism, contributing to the regulation of pathways involved in fatty acid synthesis and beta oxidation, triglyceride storage, signaling, and cellular membrane lipids.

SIGNOR-268158

P21860

P00533

0

phosphorylation

up-regulates

0.67

The erbb3 protein which possesses little or no intrinsic protein tyrosine kinase activiity is phosphorylated by the activated egf receptor protein tyrosine kinase on tyrosine residues within the yxxm sequence motif. These phosphorylated tyrosine residues interact with the p85 regulatory subunit of pi 3-kinase, which could result in the activation of the p110 catalytic subunit via a conformational mechanism.

SIGNOR-34748

Q9H4B4

Q14790

1

phosphorylation

up-regulates activity

0.338

Furthermore, we identify caspase-8 as a new substrate for Plk3. Phosphorylation occurs on T273 and results in stimulation of caspase-8 proapoptotic function.

SIGNOR-272995

Q13976

Q13507-3

1

phosphorylation

down-regulates

0.408

The present study demonstrates that human trpc3 expressed in hek293 cells forms store-operated ca2+ influx channels, the activity of which is inhibited by pkg. The inhibition is due to a direct phosphorylation of pkg on trpc3 channels at position t11 and s263.

SIGNOR-142957

O00141

P46527

1

phosphorylation

down-regulates

0.469

Activated sgk1 and p27 phosphorylation at t157, and both were inhibited by short-term rapamycin treatment and by sgk1 shrna.

SIGNOR-179117

P55283

P07737

0

null

up-regulates activity

0.335

Taken together, data obtained from MCF10A cells were consistent with the idea that Rho signaling to Dia1 and profilin-1 was essential for R-cadherin adherens junction formation.

SIGNOR-253111

P53667

P23470

0

dephosphorylation

down-regulates activity

0.26

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254711

O94916

Q8N752

0

phosphorylation

up-regulates activity

0.2

However, the siRNA knockdown of CK1α1L significantly reduced the nuclear export of OREBP/TonEBP under hypotonic conditions (Fig. 5F). Taken together, these data suggest that CK1α1L is the kinase that phosphorylates Ser-158 in the regulation of OREBP/TonEBP export.

SIGNOR-274111

Q13614

O95248

2

binding

up-regulates activity

0.635

We also demonstrate that MTMR2 interacts with MTMR5 via its coiled-coil domain and that mutations in the coiled-coil domain of either MTMR2 or MTMR5 abrogate this interaction. Through this interaction, MTMR5 increases the enzymatic activity of MTMR2 and dictates its subcellular localization.

SIGNOR-269803

Q9H171

Q9Y572

2

binding

up-regulates activity

0.637

ZBP1 initiates RIPK3-driven cell death by sensing IAV RNA and activating RIPK3. Here, we show that replicating IAV generates Z-RNAs, which activate ZBP1 in the nucleus of infected cells. ZBP1 then initiates RIPK3-mediated MLKL activation in the nucleus, resulting in nuclear envelope disruption, leakage of DNA into the cytosol, and eventual necroptosis.

SIGNOR-266430

P63092

P43088

2

binding

up-regulates activity

0.373

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚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-256810

Q02086

P10914

2

binding

up-regulates activity

0.339

Sp2 could be also able to interact with IRF-1 and this interaction is also observed on DNA indicating that by this way Sp2 is able to modulate IRF-1 transcriptional activity.

SIGNOR-226478

Q15835

Q13009

1

phosphorylation

down-regulates activity

0.2

For example, RhoK phosphorylates and inhibits TIAM1, STEF, and PAR3; disrupts the polarity complex; and prevents Rac activation ( xref ).

SIGNOR-279995

Q16539

P13726

1

phosphorylation

down-regulates

0.291

We previously showed that the phosphorylation of ser253 within the cytoplasmic domain of human tissue factor (tf) initiates the incorporation and release of this protein into cell-derived microparticles. Furthermore, subsequent phosphorylation of ser258 terminates this process. Our current study has identified p38_ as a major kinase, responsible for the phosphorylation of ser258 within the cytoplasmic domain of tf

SIGNOR-199868

P31943

Q9UKA9

2

binding

up-regulates activity

0.389

Splicing of the c-src N1 exon in neuronal cells depends in part on an intronic cluster of RNA regulatory elements called the downstream control sequence (DCS). |nPTB binds more stably to the DCS RNA than PTB does but is a weaker repressor of splicing in vitro. nPTB also greatly enhances the binding of two other proteins, hnRNP H and KSRP, to the DCS RNA.

SIGNOR-261269