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
P30989	P30990	2	binding	up-regulates	0.93	The rat neurotensin receptor cdna sequence was transfected in chinese hamster ovary cells and cellular clones which stably express the corresponding protein were isolated and characterized. The scatchard analysis of the specific binding of [3h]neurotensin indicated a kd value of 0.45 +/- 0.08 nm and a bmax value of 3.27 +/- 0.29 pmol/mg of protein. ...Neurotensin Stimulated the phosphoinositides hydrolysis	SIGNOR-17369
O43623	Q9ULU4	0	transcriptional regulation	down-regulates quantity by repression	0.2	Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported	SIGNOR-262038
Q9Y4R8	P68400	0	phosphorylation	down-regulates	0.2	Here we report that tel2 and tti1 are targeted for degradation within mtorc1 by the scffbxo9 ubiquitin ligase to adjust mtor signalling to growth factor availability. This process is primed by ck2, which translocates to the cytoplasm to mediate mtorc1-specific phosphorylation of tel2/tti1. ere, we show that tel2 is constitutively phosphorylated on conserved serines 487 and 491 by casein kinase 2 (ck2)	SIGNOR-200202
Q9HC29	P08238	2	binding	up-regulates quantity by stabilization	0.321	Nod2 is constitutively associated with a chaperone protein, Hsp90, which is required for Nod2 stability and protects Nod2 from degradation.	SIGNOR-252415
P08151	Q13547	0	deacetylation	up-regulates activity	0.594	Here, we identify a mechanism whereby Hh signalling is regulated, in which acetylation of Gli1 at Lys 518 represents a transcriptional inhibitory switch, while its HDAC1-mediated deacetylation is responsible for transcriptional activation.	SIGNOR-253544
P04049	P30304	0	dephosphorylation	down-regulates	0.395	Cdc25a can act on substrates other than cdks, since it dephosphorylates the homeodomain transcription factor cut and interacts with and dephosphorylates the proto-oncogene raf-1, resulting in a significant decrease in raf-1 kinase activity	SIGNOR-32548
Q9UNH5	P04637	1	dephosphorylation	down-regulates activity	0.401	The human Cdc14 phosphatases interact with and dephosphorylate the tumor suppressor protein p53\|. Furthermore, the hCdc14 phosphatases were found to dephosphorylate p53 specifically at the p34Cdc2/clb phosphorylation site (p53-phosphor-Ser315)\|Earlier studies showed that Ser315 phosphorylation increases the sequence-specific DNA binding capacity of p53, suggesting that Ser315 phosphorylation is an activating modification	SIGNOR-248828
Q99490	P31749	0	phosphorylation	up-regulates	0.497	In addition, we have found that activated akt can bind and phosphorylate ggap2 at serine 629, which enhances gtp binding by ggap2.	SIGNOR-183543
P62136	Q9C0D0	2	binding	up-regulates activity	0.537	Phactr-1 was previously identified as protein phosphatase 1 (PP1) α-interacting protein that possesses actin-binding domains. We showed that Phactr-1 depletion decreased PP1 activity, disrupted the fine-tuning of actin polymerization and impaired lamellipodial dynamics. Taken together our results strongly suggest that Phactr-1 is a key component in the angiogenic process.	SIGNOR-260062
P09619	Q12913	0	dephosphorylation	down-regulates activity	0.582	Primary sequence determinants responsible for site-selective dephosphorylation of the PDGF beta-receptor by the receptor-like protein tyrosine phosphatase DEP-1\|DEP-1 dephosphorylation of original and chimeric phospho-peptides spanning the preferred pY1021	SIGNOR-248704
Q9H2X6	Q06413	1	phosphorylation	down-regulates activity	0.399	HIPK2 associates with the MEF2C\u2013HDAC4 complex and phosphorylates MEF2C.	SIGNOR-279192
P04637	Q00536	0	phosphorylation	down-regulates activity	0.386	In this study, we demonstrated that CDK16 phosphorylates p53 at Ser315 and promotes ubiquitination and subsequent degradation of p53.\|Together, these results suggest that CDK16 negatively regulates p53 stability at the post-translational level.	SIGNOR-278354
P07333	P07333	2	phosphorylation	down-regulates	0.2	Csf-1-mediated wild-type (wt)-csf-1r phosphorylation was not markedly affected by sfk inhibition, indicating that lack of sfk binding is not responsible for diminished y559f phosphorylation. Unexpectedly, cells expressing y559f were hyperproliferative in response to csf-1. Hyperproliferation correlated with prolonged activation of akt, erk, and stat5 in the y559f mutant. Consistent with a defect in receptor negative regulation, c-cbl tyrosine phosphorylation and csf-1r/c-cbl co-association were almost undetectable in the y559f mutant. Furthermore, y559f underwent reduced multiubiquitination and delayed receptor internalization and degradation. In conclusion, we propose that tyr559 is a switch residue that functions in kinase regulation, signal transduction and, indirectly, receptor down-regulation.	SIGNOR-127622
O75444	P49841	0	phosphorylation	down-regulates	0.26	We showed that c-maf and mafb, like mafa, are indeed phosphorylated by gsk-3/ we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity.	SIGNOR-159438
Q5H9F3	P56524	2	binding	up-regulates activity	0.427	BCoR-L1 interacts with Class II HDACs, HDAC4, HDAC5, and HDAC7, suggesting that they are involved in its function as transcriptional corepressor.	SIGNOR-259112
P53778	P04637	1	phosphorylation	up-regulates activity	0.474	Furthermore, upon activation by oncogenic ras, p38gamma stimulated the transcriptional activity of p53 by phosphorylating p53 at Ser(33), suggesting that the ability of p38gamma to mediate senescence is at least partly achieved through p53.	SIGNOR-280026
P30304	Q15418	0	phosphorylation	down-regulates	0.366	Rsk promotes g2/m transition through activating phosphorylation of cdc25a and cdc25b rsk is likely to be more active in mitotic cells than in interphase cells, as evidenced by the phosphorylation status of t359/s363 in rsk. Together, these findings indicate that rsk promotes g2/m transition in mammalian cells through activating phosphorylation of cdc25a and cdc25b.	SIGNOR-202117
Q06124	P01112	1	dephosphorylation	up-regulates activity	0.681	Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling.	SIGNOR-252094
P09471	O14842	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257184
Q7KZI7	Q7L804	1	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
Q00535	Q02078	1	phosphorylation	down-regulates activity	0.506	Cdk5-mediated inhibition of the protective effects of transcription factor mef2 in neurotoxicity-induced apoptosis.We have identified the prosurvival transcription factor mef2 as a direct nuclear target of cdk5. Cdk5 phosphorylates mef2 at a distinct serine in its transactivation domain to inhibit mef2 activity.	SIGNOR-100574
Q13434	Q8IVH8	1	ubiquitination	down-regulates quantity	0.2	MKRN4 ubiquitinated GLK at Lys650 residue.\|Remarkably, MKRN4 overexpression induced GLK protein degradation in HEK293T cells and Jurkat T cells (figure 5A and B).	SIGNOR-278658
P17252	P11831	1	phosphorylation	up-regulates	0.245	Myotonic dystrophy protein kinase (DMPK), a muscle- and neuron-restricted kinase, enhanced SRF-mediated promoter activity of the skeletal and cardiac alpha-actin genes in C2C12 myoblasts as well as in nonmyogenic cells. \| Threonine 159 in the MADS box alphaI coil was a specific phosphorylation target in vitro as well as in vivo of both DMPK and protein kinase C-alpha.	SIGNOR-188181
O43189	P31269	1	transcriptional regulation	down-regulates quantity by repression	0.286	These data support the proposed regulatory impact of particular PRC2-proteins in expression of HOXA9 and HOXA10 in NK/T-cells. In mammalian cells knockdown of PRC2 components EZH2 or PHF1 led to upregulated HOXA gene expression.	SIGNOR-260069
Q9ULW0	P52732	2	binding	down-regulates activity	0.499	Dimeric, but not monomeric, Eg5 was differentially inhibited by full-length and truncated TPX2, demonstrating that dimerization or residues in the neck region are important for the interaction of TPX2 with Eg5.	SIGNOR-265097
P46937	Q4VCS5	0	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
P30086	P05129	0	phosphorylation	up-regulates activity	0.381	Here we report that one mechanism involves dissociation of Raf kinase inhibitory protein (RKIP) from Raf-1. Classic and atypical but not novel PKC isoforms phosphorylate RKIP at serine 153 (Ser-153). RKIP Ser-153 phosphorylation by PKC either in vitro or in response to 12-O-tetradecanoylphorbol-13-acetate or epidermal growth factor causes release of RKIP from Raf-1, whereas mutant RKIP (S153V or S153E) remains bound. I	SIGNOR-249190
P00533	P04626	2	phosphorylation	up-regulates activity	0.613	Induction of cancer cell migration by epidermal growth factor is initiated by specific phosphorylation of tyrosine 1248 of c-erbB-2 receptor via EGFR. \| In summary, c-erbB-2 up-regulation switches on the cell migration program by modulating the time course of PLC-gamma1 activation.	SIGNOR-251094
P09874	Q96EP1	0	polyubiquitination	down-regulates quantity by destabilization	0.427	Here, we show that checkpoint with Forkhead-associated (FHA) and RING finger domain protein (CHFR), an E3 ubiquitin ligase, is recruited to DSBs by poly(ADP-ribose) (PAR). Moreover, CHFR ubiquitinates PAR polymerase 1 (PARP1) and regulates chromatin-associated PARP1 in vivo. Moreover, the poly-ubiquitin chain on PARP1 could be recognized by both anti-K48 and K63-linked poly-ubiquitin chain antibodies, suggesting that CHFR mediates a mixed poly-ubiquitin chain linkage on PARP1. With MG132 treatment, ubiquitinated PARP1 was significantly accumulated (Figure 4D), suggesting that the ubiquitination of PARP1 is likely involved in protein degradation. Consistently, we found that following DNA damage, PARP1 quickly dissociated from the chromatin in the wild-type cells (Figure 4F). However, in the Chfr−/− cells, the dissociation of PARP1 from the chromatin was significantly delayed.	SIGNOR-271470
Q00535	Q96PV0	1	phosphorylation	up-regulates activity	0.383	CDK5 increases recombinant SYNGAP1 activity on Ras-GAP by 98% and its Rap-GAP activity by 20%.\|Interestingly, phosphorylation of SYNGAP1 by CDK5 and CaMKII increases overall SYNGAP1 activity, but also alters the ratio of its GAP activity towards Ras- and Rap-GTPases.	SIGNOR-279157
Q96JA1	Q9ULV8	2	binding	up-regulates	0.2	Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation	SIGNOR-127301
Q16143	Q9H4B4	0	phosphorylation	down-regulates activity	0.38	Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation.	SIGNOR-189057
P51617	Q9Y4K3	2	binding	up-regulates activity	0.913	Il-1 treatment of 293 cells induces the association of traf6 with irak.	SIGNOR-44234
Q9UQR1	Q13315	0	phosphorylation	up-regulates	0.36	Here we found that zbp-89 is phosphorylated by atm kinase in vitro and in vivo. Disruption of the atm phosphorylation motif (202)sq within the zinc finger domain of zbp-89 attenuated its ability to enhance p21(waf1) activation by butyrate. Moreover, disruption of the atm phosphorylation site abrogated the ability of zbp-89 to potentiate butyrate induction of endogenous p21(waf1) expression.	SIGNOR-155634
P24941	Q13118	1	phosphorylation	up-regulates quantity	0.329	In this study we have shown that CDK2 phosphorylates KLF10 at residue Ser 206 in vivo and in vitro .\|In this study, we have shown that KLF10 protein has tightly controlled expression and that the expression level varies in a cell cycle dependent manner whereby CDK2 up-regulates activity the protein level of KLF10 through interference with the protein 's association with SIAH1.	SIGNOR-278394
P36894	O95393	2	binding	up-regulates	0.632	We showed that three orphan ligands known to be important for joint and cartilage formation (gdf6) (10), interneuron, sensory neurons, and seminal vesicle formation (gdf7) (11_13), and heart development (bmp10) (14) used the type i receptors alk3 or alk6 and the type ii receptors bmprii or actriia to activate the smad1/5/8 proteins.	SIGNOR-139052
P27987	P17252	0	null	down-regulates activity	0.359	However, when assayed in the presence of calcium/calmodulin, the activity of the B isoform was decreased following phosphorylation by either protein kinase.	SIGNOR-248990
P01112	P50148	2	binding	up-regulates	0.641	Galfaq/11 subunits also activate p21ras	SIGNOR-50104
P08754	P30550	2	binding	up-regulates activity	0.268	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-257159
Q14451	P07949	2	binding	up-regulates	0.571	Grb7 and grb10, likely relay signals emanating from ret to other, as yet, unidentified targets within the cell	SIGNOR-41765
P35968	Q05397	1	null	up-regulates activity	0.496	Here we show that genetic or pharmacological FAK inhibition in ECs prevents VEGF-stimulated permeability downstream of VEGF receptor or Src tyrosine kinase activation in vivo. VEGF promotes tension-independent FAK activation	SIGNOR-261945
Q9NYY3	P37840	1	phosphorylation	down-regulates activity	0.478	Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation. Pathological serine 129 phosphorylation regulates membrane accumulation of mutant alpha-synuclein.	SIGNOR-182155
P17612	P41240	1	phosphorylation	up-regulates activity	0.338	Activation of the cooh-terminal src kinase (csk) by camp-dependent protein kinase inhibits signaling through the t cell receptor.Pka phosphorylates csk at s364 in vitro and in vivo leading to a two- to fourfold increase in csk activity that is necessary for camp-mediated inhibition of tcr-induced interleukin 2 secretion.	SIGNOR-105229
P0DTD1-PRO_0000449630	Q9UHD2	2	binding	down-regulates activity	0.2	We use unbiased screening to identify SARS-CoV-2 proteins that antagonize type I interferon (IFN-I) response. We found three proteins that antagonize IFN-I production via distinct mechanisms: nonstructural protein 6 (nsp6) binds TANK binding kinase 1 (TBK1) to suppress interferon regulatory factor 3 (IRF3) phosphorylation, nsp13 binds and blocks TBK1 phosphorylation, and open reading frame 6 (ORF6) binds importin Karyopherin α 2 (KPNA2) to inhibit IRF3 nuclear translocation. the results indicate that (1) nsp6 binds to TBK1 without affecting TBK1 phosphorylation, but the nsp6/TBK1 interaction decreases IRF3 phosphorylation, which leads to reduced IFN-β production; and (2) nsp13 binds and inhibits TBK1 phosphorylation, resulting in decreased IRF3 activation and IFN-β production (Figure 2F).	SIGNOR-262512
P20936	P09619	2	binding	up-regulates	0.58	The gtpase activating protein (gap) of ras binds only to beta-receptors / we have previously shown that the binding site for gtpase activating protein of ras (rasgap) in the pdgf beta-receptor, tyr771, is phosphorylated to a much lower extent in the heterodimeric configuration of pdgf alpha- and beta-receptors, compared to the pdgf beta-receptor homodimer. / the decreased recruitment of the rasgap to the receptor leads to prolonged activation of the ras/map kinase pathway	SIGNOR-115843
Q15637	Q8TAS1	0	phosphorylation	up-regulates	0.406	Sf1 is phosphorylated on serines 80 and 82 in vitro and in vivo. Kis can phosphorylate sf1f on serine 80 and 82 with a high efficiency that particularly relies on the anchoring of its uhm domain to sf1. Serine phosphorylation of a conserved ser80-pro81-ser82-pro83 motif rigidifies a long unstructured linker in the sf1 helix hairpin and slightly enhances rna binding.	SIGNOR-199797
Q8IXJ9	P19793	2	binding	up-regulates activity	0.284	In this study, we demonstrate that mammalian ASXL1 interacts with the AF-2 AD core of RAR (and RXR) through a novel, promiscuous NR box (LVMQLL) and enhances transcriptional activity of the receptors in certain cells.	SIGNOR-255911
P49841	P03372	1	phosphorylation	up-regulates	0.34	The gsk-3 inhibitor lithium chloride was used to determine the role of gsk-3 in phosphorylation of ser-102, -104, and -106 and ser-118 in vivo and to explore the role of these serines in the regulation of eralpha function. Treatment of cells with lithium chloride resulted in dephosphorylation of ser-104 and -106 and ser-118, which suggests these serine residues as targets for gsk-3 in vivo. Our results further suggest that eralpha phosphorylation by gsk-3 stabilizes eralpha under resting conditions and modulates eralpha transcriptional activity upon ligand binding. Estradiol and phorbol ester cause phosphorylation of serine 118 in the human estrogen receptor. Potentiation of human estrogen receptor alpha transcriptional activation through phosphorylation of serines 104 and 106 by the cyclin a-cdk2 complex.	SIGNOR-139316
P10636	Q9H992	0	ubiquitination	down-regulates activity	0.2	We have identified and characterized axotrophin, a protein that binds and preferentially mono-ubiquitinates tau protein.	SIGNOR-278655
O60825	Q13131	0	phosphorylation	up-regulates activity	0.464	Heart 6-phosphofructo-2-kinase activation by insulin results from ser-466 and ser-483 phosphorylation and requires 3-phosphoinositide-dependent kinase-1, but not protein kinase b.	SIGNOR-84061
P24941	P28324	1	phosphorylation	up-regulates activity	0.363	Phosphorylation of ELK4 at Thr194 and Ser387 by CDK2 is required for EGF-induced cell transformation.	SIGNOR-278210
P55075	P19622	0	transcriptional regulation	down-regulates quantity by repression	0.416	Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression.	SIGNOR-265801
P18075	Q13873	2	binding	up-regulates	0.804	In transfected cos-1 cells, osteogenic protein (op)-1/bmp-7, and less efficiently bmp-4, bound to bmpr-ii. Bmpr-ii bound ligands only weakly alone, but the binding was facilitated by the presence of previously identified type i receptors for bmps. Binding of op-1/bmp-7 to bmpr-ii was also observed in nontransfected cell lines. Moreover, a transcriptional activation signal was transduced by bmpr-ii in the presence of type i receptors after stimulation by op-1/bmp-7.	SIGNOR-30512
Q16665	Q9P0U3	0	desumoylation	up-regulates	0.325	Sumo-specific protease 1 is essential for stabilization of hif1alpha during hypoxia / our results support a model in which sumoylated hif1_ is unstable but can be stabilized when sumo is removed by senp1	SIGNOR-158891
Q9UHD2	Q96CV9	2	phosphorylation	up-regulates activity	0.789	Given that TBK1 can phosphorylate OPTN on S177, S473 and S513 in response to mitochondrial depolarization, we explored the function of these events in vivo.\|Phosphorylation of OPTN on S473 and S513 promotes TBK1 activation and recruitment of OPTN to depolarized mitochondria.	SIGNOR-278170
O14737	O14829	0	dephosphorylation	down-regulates quantity by destabilization	0.349	Here, we report that the serine/threonine phosphatase PPEF-1 interacts with and dephosphorylates PDCD5 at Ser 119, which leads to PDCD5 destabilization.\|These results demonstrate that PPEF-1 reduces PDCD5 stability via PDCD5 dephosphorylation.	SIGNOR-277008
Q5JWF2	P32245	0	null	up-regulates activity	0.521	We hypothesize that XLŒ±s may be involved in this regulatory loop by coupling to melanocortin receptors 3 and 4 in the hypothalamus.	SIGNOR-253067
Q00535	Q96KR7	1	phosphorylation	down-regulates quantity	0.2	We show that scapinin is phosphorylated at a highly conserved site in the central region of the protein (Ser-277) by Cdk5 in vitro. Expression of a scapinin phospho-mimetic mutant (S277D) restored normal axon elongation without affecting actin binding. Instead, phosphorylated scapinin was sequestered in the cytoplasm of neurons and away from the axon.	SIGNOR-273607
P28482	Q96PH1	1	phosphorylation	up-regulates	0.325	These results suggest that the mek/erk1/2 pathway is necessary but not sufficient to regulate the pma-dependent activation of nox5.	SIGNOR-171847
O60610	P55283	1	null	up-regulates activity	0.2	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-253110
P29317	P29353	2	binding	up-regulates	0.616	We also show that the interaction of epha2 with grb2 is indirect and mediated by shc and that this complex is necessary for epha2-mediated activation of erk kinases.	SIGNOR-94804
Q00987	Q9NQU5	0	phosphorylation	up-regulates activity	0.2	We also showed that PAK6 phosphorylates Mdm2 on Thr-158 and Ser-186, which is critical for AR ubiquitin-mediated degradation.	SIGNOR-276428
Q96JH7	P06493	0	phosphorylation	down-regulates activity	0.537	We clarified that VCIP135, an essential factor in both p97 membrane fusion pathways, is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis and that this phosphorylated VCIP135 does not bind to p97.	SIGNOR-265038
P18848	Q9UGM6	1	transcriptional regulation	up-regulates quantity by expression	0.246	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-269430
Q9Y286	O14543	2	binding	down-regulates quantity by destabilization	0.372	SOCS proteins can act as E3 ligases by forming a complex with Elongin B/C and Cul5/Rbx1/2.SOCS3 targets Siglec 7 for degradation	SIGNOR-272642
Q9NP71	P25445	1	transcriptional regulation	up-regulates quantity by expression	0.2	The present study provides evidence for a direct and dominant role of ChREBP in the glucose regulation of two key liver lipogenic enzymes, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS)	SIGNOR-267947
P03952	P01042	1	cleavage	up-regulates activity	0.779	Bradykinin is a nonapeptide composed of the sequence Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg and functions as an inflammatory mediator. BK is the product of the kallikrein–kinin system following activation of FXII. FXIIa leads to proteolysis of PK, and the resulting PKa cleaves HK to generate BK (Figure 1).	SIGNOR-263548
P04626	Q02297	2	binding	up-regulates	0.792	Direct interaction between heregulin and the two proteins was demonstrated by chemical cross-linking experiments using 125i-heregulin followed by immunoprecipitation with antibodies specific for erbb2 or erbb3.	SIGNOR-26875
Q8N2W9	P84022	2	binding	down-regulates	0.648	Piasy binds most strongly with smad3 and also associates with other receptor-regulated smads and smad4. smad3, smad4, and piasy can form a ternary complex. Piasy does not inhibit smad complex binding to dna, but it represses smad transcriptional activity.	SIGNOR-104538
P68400	Q13351	1	phosphorylation	up-regulates activity	0.344	Regulation of erythroid Krppel-like factor (EKLF) transcriptional activity by phosphorylation of a protein kinase casein kinase II site within its interaction domain. the transactivation capability of EKLF is augmented by co-transfection of CKIIalpha. in vitro assays demonstrate that CKIIalpha interacts with EKLF, and that the EKLF interaction domain is phosphorylated by CKII only at Thr-41	SIGNOR-241361
P53350	Q13158	1	phosphorylation	down-regulates activity	0.459	Fas-associated death domain-containing protein (FADD) was first identified as an adapter molecule involved in formation of a death-inducing signaling complex upon Fas stimulation\| Plk1 phosphorylates fadd at ser-194 in response to treatment with taxol Phosphorylation by polo-like kinase 1 induces the tumor-suppressing activity of FADD	SIGNOR-168204
Q9UQ88	P24522	2	binding	down-regulates activity	0.2	GADD45alpha inhibits CDK11p58 kinase activity\|We identified CDK11p58 as an interaction partner of GADD45α by co-immunoprecipitation analysis. We corroborated these data by co-immunoprecipitation in vitro translation assays, showing that all three members of the GADD45 family interact with CDK11p58.	SIGNOR-273023
P05106	Q15118	0	phosphorylation	down-regulates activity	0.306	PDK1 specifically phosphorylates Thr-753 in 3. Our data argue that phosphorylation of Thr-753, which is conserved in many subunits, reduces the ability of PTB-containing proteins to bind the NXX(pY) motif in 3.	SIGNOR-250264
Q96EP1	P51532	1	polyubiquitination	down-regulates quantity by destabilization	0.333	Here we report that CHFR interacts with BRG1, SNF5, and BAF60a of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and that SRG3/mBAF155 stabilizes these components by blocking their interaction with CHFR. These results suggest that CHFR enhances the degradation of the components of the SWI/SNF-like BAF complex by inducing their poly-ubiquitination.	SIGNOR-271457
Q14457	Q13464	0	phosphorylation	up-regulates activity	0.415	Beclin1 is phosphorylated by ROCK1 at T119.	SIGNOR-278198
P06401	Q9Y618	0	acetylation	down-regulates	0.588	In this study we assessed the effect of smrt and dax-1 on ar and pr activity in the presence of both agonists and partial antagonists. We show that smrt and dax-1 repress agonist-dependent activity of both receptors, and the mechanism of repression includes disruption of the receptor dimer interactions rather than recruitment of histone deacetylases.	SIGNOR-101289
P07948	P11912	1	phosphorylation	up-regulates activity	0.738	Y182 of CD79a appears to be the initial and preferred site of Ag receptor phosphorylation by Src family kinases. In vitro, Src family Lyn and Fyn predominantly phosphorylate this residue in CD79a, and Y195 does so in CD79b. phosphorylation of Y182 alone can lead to further kinase activation and/or effector focusing necessary for phosphorylation of certain downstream targets, such as p62, p110, and Shc, but not others, such as Vav.	SIGNOR-251397
P15311	P25098	0	phosphorylation	up-regulates	0.2	Grk2 phosphorylates glutathione s-transferase (gst)-ezrin, but not an ezrin fusion protein lacking threonine 567 (t567), in vitro. These results suggest that t567, the regulatory phosphorylation site responsible for maintaining ezrin in its active conformation, represents the principle site of grk2-mediated phosphorylation.	SIGNOR-135622
Q92585	Q9UM47	2	binding	up-regulates	0.79	Maml1 binds to the ankyrin repeat domain of all four mammalian notch receptors, forms a dna-binding complex with icn and rbp-jkappa, and amplifies notch-induced transcription of hes1.	SIGNOR-84838
Q9UBY8	P67775	2	binding	up-regulates activity	0.2	CLN8 interacts with ceramide binding proteins PP2A and I2PP2A. We showed that the phosphorylation levels of several substrates of PP2A, namely Akt, S6 kinase, and GSK3β, were decreased in CLN8 disease patient fibroblasts. This reduction can be reversed by inhibiting PP2A phosphatase activity with cantharidin, suggesting a higher PP2A activity in CLN8-deficient cells. The phosphorylation levels of PP2A substrates are decreased in the absence of CLN8.	SIGNOR-265583
Q86YS7	P31751	0	phosphorylation	up-regulates activity	0.513	MS analysis of an HA-CDP138 sample from the in vitro kinase assay revealed that active Akt2 induces CDP138 phosphorylation at serine (Ser)197, which lies within a consensus Akt substrate motif RQRLIS 197 ( xref ).	SIGNOR-279585
Q9UQD0	P49841	0	phosphorylation	up-regulates activity	0.2	In vivo genetic manipulations demonstrate that GSK3β and Nav1.6 are molecular determinants of MSN excitability and that silencing of GSK3β prevents maladaptive plasticity of IC MSNs. In vitro studies reveal direct interaction of GSK3β with Nav1.6 and phosphorylation at Nav1.6T1936 by GSK3β. A GSK3β-Nav1.6T1936 competing peptide reduces MSNs excitability in IC, but not EC rats. These results identify GSK3β regulation of Nav1.6 as a biosignature of MSNs maladaptive plasticity.	SIGNOR-275763
P08069	P01344	2	binding	up-regulates activity	0.821	These results strongly suggest that the IGF2–IGF1R–IRS2 axis signals to PI3K in CRC and imply that therapeutic targeting of the pathway could act to block PI3K activity in this subset of patients.	SIGNOR-251495
P19793	P45985	0	phosphorylation	down-regulates	0.2	Phosphorylation by mkk4/sek1 had profound effects on the biochemical properties of rxr, inhibiting the expression of genes activated by rxr-retinoic acid receptor complexes. Tyr-249 in the rxr de region was required for the inhibitory effect of mkk4/sek1.	SIGNOR-80619
Q05513	Q9Y243	1	phosphorylation	up-regulates activity	0.546	Full activation of the PKB enzyme requires phosphorylation of a threonine in the activation	SIGNOR-249153
P07359	P78536	0	cleavage	down-regulates activity	0.284	GPIbα is shed by metalloproteases such as ADAM17, a process that releases a soluble GPIbα fragment termed glycocalicin. ADAM17 cleaves within the GPIbα-based peptide (LRGV465LK) through a mechanism that is only partially understood [42]. GPIbα shedding has been shown to be constitutive but it can be increased by activation of protein kinases C (PKC) or inhibition of calmodulin [42, 43]. Shedding leads to decreased receptor density	SIGNOR-261861
Q9BXY4	O75473	2	binding	up-regulates	0.657	Here we demonstrate that lgr4 and lgr5 bind the r-spondins with high affinity and mediate the potentiation of wnt/betBeta-catenin signaling by enhancing wnt-induced lrp6 phosphorylation	SIGNOR-174535
P01112	P42336	2	binding	up-regulates	0.924	In vivo, dominant negative ras mutant n17 inhibits growth factor induced production of 3' phosphorylated phosphoinositides in pc12 cells, and transfection of ras, but not raf, into cos cells results in a large elevation in the level of these lipids. Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85. it was also described that ras interacts with pi3k in a direct manner. lysine residue 227 is essential for the interaction of ras with pi3k	SIGNOR-35878
O14994	P27361	0	phosphorylation	up-regulates	0.2	A rare, missense polymorphism, s470n, was identified in the synapsin iii gene and appeared more frequently in individuals with schizophrenia than in controls. Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action.	SIGNOR-121402
P56945	Q6P5Z2	2	binding	up-regulates activity	0.2	Taken together, the data suggest that p130Cas expression induces PKN3 activation and this activation is independent of p130Cas–PKN3 interaction.	SIGNOR-264573
Q9H492	Q8IXH6	2	binding	up-regulates	0.408	Tp53inp2 is a scaffold protein that recruits lc3 and/or lc3-related proteins to the autophagosome membrane by interacting with the transmembrane protein vmp1	SIGNOR-182614
Q9H0X6	P08670	1	ubiquitination	down-regulates quantity by destabilization	0.2	Here, we show that RING finger protein 208 (RNF208) decreases the stability of soluble Vimentin protein through a polyubiquitin-mediated proteasomal degradation pathway, thereby suppressing metastasis of TNBC cells	SIGNOR-269051
Q9NP59	Q16236	0	transcriptional regulation	up-regulates quantity by expression	0.257	NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. SLC40A1 is a target gene of NFE2L2, with a putative ARE identified approximately -7 kb upstream of the SLC40A1 core promoter.	SIGNOR-279863
O75385	Q9Y2M5	2	binding	down-regulates quantity by destabilization	0.249	Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination. KLHL20 promotes ubiquitination of phagophore-residing VPS34 and Beclin-1	SIGNOR-272413
Q9ULB1	Q8NFZ4	2	binding	up-regulates activity	0.825	The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites.	SIGNOR-265452
P09471	P28336	2	binding	up-regulates activity	0.268	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-257248
P06493	O75154	1	phosphorylation	up-regulates quantity	0.2	FIP3 is phosphorylated on S102 in a cell cycle-dependent manner. We identify four sites of phosphorylation of FIP3 in vivo, S-102, S-280, S-347 and S-450 and identify S-102 as a target for Cdk1-cyclin B in vitro. Of these, we show that S-102 is phosphorylated in metaphase and is dephosphorylated as cells enter telophase.	SIGNOR-273588
P61328	P35499	2	binding	down-regulates activity	0.255	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-253432
Q13049	Q9H9R9	1	ubiquitination	down-regulates quantity by destabilization	0.2	TRIM32 is an E3 ubiquitin ligase for dysbindin. TRIM32 targets dysbindin for degradation.	SIGNOR-271422
Q14940	P68400	0	phosphorylation	down-regulates activity	0.2	CK2 phosphorylation of an acidic Ser/Thr di-isoleucine motif in the Na+/H+ exchanger NHE5 isoform promotes association with beta-arrestin2 and endocytosis	SIGNOR-276250

P30989

P30990

2

binding

up-regulates

0.93

The rat neurotensin receptor cdna sequence was transfected in chinese hamster ovary cells and cellular clones which stably express the corresponding protein were isolated and characterized. The scatchard analysis of the specific binding of [3h]neurotensin indicated a kd value of 0.45 +/- 0.08 nm and a bmax value of 3.27 +/- 0.29 pmol/mg of protein. ...Neurotensin Stimulated the phosphoinositides hydrolysis

SIGNOR-17369

O43623

Q9ULU4

0

transcriptional regulation

down-regulates quantity by repression

0.2

Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported

SIGNOR-262038

Q9Y4R8

P68400

0

phosphorylation

down-regulates

0.2

Here we report that tel2 and tti1 are targeted for degradation within mtorc1 by the scffbxo9 ubiquitin ligase to adjust mtor signalling to growth factor availability. This process is primed by ck2, which translocates to the cytoplasm to mediate mtorc1-specific phosphorylation of tel2/tti1. ere, we show that tel2 is constitutively phosphorylated on conserved serines 487 and 491 by casein kinase 2 (ck2)

SIGNOR-200202

Q9HC29

P08238

2

binding

up-regulates quantity by stabilization

0.321

Nod2 is constitutively associated with a chaperone protein, Hsp90, which is required for Nod2 stability and protects Nod2 from degradation.

SIGNOR-252415

P08151

Q13547

0

deacetylation

up-regulates activity

0.594

Here, we identify a mechanism whereby Hh signalling is regulated, in which acetylation of Gli1 at Lys 518 represents a transcriptional inhibitory switch, while its HDAC1-mediated deacetylation is responsible for transcriptional activation.

SIGNOR-253544

P04049

P30304

0

dephosphorylation

down-regulates

0.395

Cdc25a can act on substrates other than cdks, since it dephosphorylates the homeodomain transcription factor cut and interacts with and dephosphorylates the proto-oncogene raf-1, resulting in a significant decrease in raf-1 kinase activity

SIGNOR-32548

Q9UNH5

P04637

1

dephosphorylation

down-regulates activity

0.401

The human Cdc14 phosphatases interact with and dephosphorylate the tumor suppressor protein p53|. Furthermore, the hCdc14 phosphatases were found to dephosphorylate p53 specifically at the p34Cdc2/clb phosphorylation site (p53-phosphor-Ser315)|Earlier studies showed that Ser315 phosphorylation increases the sequence-specific DNA binding capacity of p53, suggesting that Ser315 phosphorylation is an activating modification

SIGNOR-248828

Q99490

P31749

0

phosphorylation

up-regulates

0.497

In addition, we have found that activated akt can bind and phosphorylate ggap2 at serine 629, which enhances gtp binding by ggap2.

SIGNOR-183543

P62136

Q9C0D0

2

binding

up-regulates activity

0.537

Phactr-1 was previously identified as protein phosphatase 1 (PP1) α-interacting protein that possesses actin-binding domains. We showed that Phactr-1 depletion decreased PP1 activity, disrupted the fine-tuning of actin polymerization and impaired lamellipodial dynamics. Taken together our results strongly suggest that Phactr-1 is a key component in the angiogenic process.

SIGNOR-260062

P09619

Q12913

0

dephosphorylation

down-regulates activity

0.582

Primary sequence determinants responsible for site-selective dephosphorylation of the PDGF beta-receptor by the receptor-like protein tyrosine phosphatase DEP-1|DEP-1 dephosphorylation of original and chimeric phospho-peptides spanning the preferred pY1021

SIGNOR-248704

Q9H2X6

Q06413

1

phosphorylation

down-regulates activity

0.399

HIPK2 associates with the MEF2C\u2013HDAC4 complex and phosphorylates MEF2C.

SIGNOR-279192

P04637

Q00536

0

phosphorylation

down-regulates activity

0.386

In this study, we demonstrated that CDK16 phosphorylates p53 at Ser315 and promotes ubiquitination and subsequent degradation of p53.|Together, these results suggest that CDK16 negatively regulates p53 stability at the post-translational level.

SIGNOR-278354

P07333

2

phosphorylation

down-regulates

0.2

Csf-1-mediated wild-type (wt)-csf-1r phosphorylation was not markedly affected by sfk inhibition, indicating that lack of sfk binding is not responsible for diminished y559f phosphorylation. Unexpectedly, cells expressing y559f were hyperproliferative in response to csf-1. Hyperproliferation correlated with prolonged activation of akt, erk, and stat5 in the y559f mutant. Consistent with a defect in receptor negative regulation, c-cbl tyrosine phosphorylation and csf-1r/c-cbl co-association were almost undetectable in the y559f mutant. Furthermore, y559f underwent reduced multiubiquitination and delayed receptor internalization and degradation. In conclusion, we propose that tyr559 is a switch residue that functions in kinase regulation, signal transduction and, indirectly, receptor down-regulation.

SIGNOR-127622

O75444

P49841

0

phosphorylation

down-regulates

0.26

We showed that c-maf and mafb, like mafa, are indeed phosphorylated by gsk-3/ we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity.

SIGNOR-159438

Q5H9F3

P56524

2

binding

up-regulates activity

0.427

BCoR-L1 interacts with Class II HDACs, HDAC4, HDAC5, and HDAC7, suggesting that they are involved in its function as transcriptional corepressor.

SIGNOR-259112

P53778

P04637

1

phosphorylation

up-regulates activity

0.474

Furthermore, upon activation by oncogenic ras, p38gamma stimulated the transcriptional activity of p53 by phosphorylating p53 at Ser(33), suggesting that the ability of p38gamma to mediate senescence is at least partly achieved through p53.

SIGNOR-280026

P30304

Q15418

0

phosphorylation

down-regulates

0.366

Rsk promotes g2/m transition through activating phosphorylation of cdc25a and cdc25b rsk is likely to be more active in mitotic cells than in interphase cells, as evidenced by the phosphorylation status of t359/s363 in rsk. Together, these findings indicate that rsk promotes g2/m transition in mammalian cells through activating phosphorylation of cdc25a and cdc25b.

SIGNOR-202117

Q06124

P01112

1

dephosphorylation

up-regulates activity

0.681

Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling.

SIGNOR-252094

P09471

O14842

2

binding

up-regulates activity

0.2

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

SIGNOR-257184

Q7KZI7

Q7L804

1

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

Q00535

Q02078

1

phosphorylation

down-regulates activity

0.506

Cdk5-mediated inhibition of the protective effects of transcription factor mef2 in neurotoxicity-induced apoptosis.We have identified the prosurvival transcription factor mef2 as a direct nuclear target of cdk5. Cdk5 phosphorylates mef2 at a distinct serine in its transactivation domain to inhibit mef2 activity.

SIGNOR-100574

Q13434

Q8IVH8

1

ubiquitination

down-regulates quantity

0.2

MKRN4 ubiquitinated GLK at Lys650 residue.|Remarkably, MKRN4 overexpression induced GLK protein degradation in HEK293T cells and Jurkat T cells (figure 5A and B).

SIGNOR-278658

P17252

P11831

1

phosphorylation

up-regulates

0.245

Myotonic dystrophy protein kinase (DMPK), a muscle- and neuron-restricted kinase, enhanced SRF-mediated promoter activity of the skeletal and cardiac alpha-actin genes in C2C12 myoblasts as well as in nonmyogenic cells. | Threonine 159 in the MADS box alphaI coil was a specific phosphorylation target in vitro as well as in vivo of both DMPK and protein kinase C-alpha.

SIGNOR-188181

O43189

P31269

1

transcriptional regulation

down-regulates quantity by repression

0.286

These data support the proposed regulatory impact of particular PRC2-proteins in expression of HOXA9 and HOXA10 in NK/T-cells. In mammalian cells knockdown of PRC2 components EZH2 or PHF1 led to upregulated HOXA gene expression.

SIGNOR-260069

Q9ULW0

P52732

2

binding

down-regulates activity

0.499

Dimeric, but not monomeric, Eg5 was differentially inhibited by full-length and truncated TPX2, demonstrating that dimerization or residues in the neck region are important for the interaction of TPX2 with Eg5.

SIGNOR-265097

P46937

Q4VCS5

0

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

P30086

P05129

0

phosphorylation

up-regulates activity

0.381

Here we report that one mechanism involves dissociation of Raf kinase inhibitory protein (RKIP) from Raf-1. Classic and atypical but not novel PKC isoforms phosphorylate RKIP at serine 153 (Ser-153). RKIP Ser-153 phosphorylation by PKC either in vitro or in response to 12-O-tetradecanoylphorbol-13-acetate or epidermal growth factor causes release of RKIP from Raf-1, whereas mutant RKIP (S153V or S153E) remains bound. I

SIGNOR-249190

P00533

P04626

2

phosphorylation

up-regulates activity

0.613

Induction of cancer cell migration by epidermal growth factor is initiated by specific phosphorylation of tyrosine 1248 of c-erbB-2 receptor via EGFR. | In summary, c-erbB-2 up-regulation switches on the cell migration program by modulating the time course of PLC-gamma1 activation.

SIGNOR-251094

P09874

Q96EP1

0

polyubiquitination

down-regulates quantity by destabilization

0.427

Here, we show that checkpoint with Forkhead-associated (FHA) and RING finger domain protein (CHFR), an E3 ubiquitin ligase, is recruited to DSBs by poly(ADP-ribose) (PAR). Moreover, CHFR ubiquitinates PAR polymerase 1 (PARP1) and regulates chromatin-associated PARP1 in vivo. Moreover, the poly-ubiquitin chain on PARP1 could be recognized by both anti-K48 and K63-linked poly-ubiquitin chain antibodies, suggesting that CHFR mediates a mixed poly-ubiquitin chain linkage on PARP1. With MG132 treatment, ubiquitinated PARP1 was significantly accumulated (Figure 4D), suggesting that the ubiquitination of PARP1 is likely involved in protein degradation. Consistently, we found that following DNA damage, PARP1 quickly dissociated from the chromatin in the wild-type cells (Figure 4F). However, in the Chfr−/− cells, the dissociation of PARP1 from the chromatin was significantly delayed.

SIGNOR-271470

Q00535

Q96PV0

1

phosphorylation

up-regulates activity

0.383

CDK5 increases recombinant SYNGAP1 activity on Ras-GAP by 98% and its Rap-GAP activity by 20%.|Interestingly, phosphorylation of SYNGAP1 by CDK5 and CaMKII increases overall SYNGAP1 activity, but also alters the ratio of its GAP activity towards Ras- and Rap-GTPases.

SIGNOR-279157

Q96JA1

Q9ULV8

2

binding

up-regulates

0.2

Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation

SIGNOR-127301

Q16143

Q9H4B4

0

phosphorylation

down-regulates activity

0.38

Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation.

SIGNOR-189057

P51617

Q9Y4K3

2

binding

up-regulates activity

0.913

Il-1 treatment of 293 cells induces the association of traf6 with irak.

SIGNOR-44234

Q9UQR1

Q13315

0

phosphorylation

up-regulates

0.36

Here we found that zbp-89 is phosphorylated by atm kinase in vitro and in vivo. Disruption of the atm phosphorylation motif (202)sq within the zinc finger domain of zbp-89 attenuated its ability to enhance p21(waf1) activation by butyrate. Moreover, disruption of the atm phosphorylation site abrogated the ability of zbp-89 to potentiate butyrate induction of endogenous p21(waf1) expression.

SIGNOR-155634

P24941

Q13118

1

phosphorylation

up-regulates quantity

0.329

In this study we have shown that CDK2 phosphorylates KLF10 at residue Ser 206 in vivo and in vitro .|In this study, we have shown that KLF10 protein has tightly controlled expression and that the expression level varies in a cell cycle dependent manner whereby CDK2 up-regulates activity the protein level of KLF10 through interference with the protein 's association with SIAH1.

SIGNOR-278394

P36894

O95393

2

binding

up-regulates

0.632

We showed that three orphan ligands known to be important for joint and cartilage formation (gdf6) (10), interneuron, sensory neurons, and seminal vesicle formation (gdf7) (11_13), and heart development (bmp10) (14) used the type i receptors alk3 or alk6 and the type ii receptors bmprii or actriia to activate the smad1/5/8 proteins.

SIGNOR-139052

P27987

P17252

0

null

down-regulates activity

0.359

However, when assayed in the presence of calcium/calmodulin, the activity of the B isoform was decreased following phosphorylation by either protein kinase.

SIGNOR-248990

P01112

P50148

2

binding

up-regulates

0.641

Galfaq/11 subunits also activate p21ras

SIGNOR-50104

P08754

P30550

2

binding

up-regulates activity

0.268

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-257159

Q14451

P07949

2

binding

up-regulates

0.571

Grb7 and grb10, likely relay signals emanating from ret to other, as yet, unidentified targets within the cell

SIGNOR-41765

P35968

Q05397

1

null

up-regulates activity

0.496

Here we show that genetic or pharmacological FAK inhibition in ECs prevents VEGF-stimulated permeability downstream of VEGF receptor or Src tyrosine kinase activation in vivo. VEGF promotes tension-independent FAK activation

SIGNOR-261945

Q9NYY3

P37840

1

phosphorylation

down-regulates activity

0.478

Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation. Pathological serine 129 phosphorylation regulates membrane accumulation of mutant alpha-synuclein.

SIGNOR-182155

P17612

P41240

1

phosphorylation

up-regulates activity

0.338

Activation of the cooh-terminal src kinase (csk) by camp-dependent protein kinase inhibits signaling through the t cell receptor.Pka phosphorylates csk at s364 in vitro and in vivo leading to a two- to fourfold increase in csk activity that is necessary for camp-mediated inhibition of tcr-induced interleukin 2 secretion.

SIGNOR-105229

P0DTD1-PRO_0000449630

Q9UHD2

2

binding

down-regulates activity

0.2

We use unbiased screening to identify SARS-CoV-2 proteins that antagonize type I interferon (IFN-I) response. We found three proteins that antagonize IFN-I production via distinct mechanisms: nonstructural protein 6 (nsp6) binds TANK binding kinase 1 (TBK1) to suppress interferon regulatory factor 3 (IRF3) phosphorylation, nsp13 binds and blocks TBK1 phosphorylation, and open reading frame 6 (ORF6) binds importin Karyopherin α 2 (KPNA2) to inhibit IRF3 nuclear translocation. the results indicate that (1) nsp6 binds to TBK1 without affecting TBK1 phosphorylation, but the nsp6/TBK1 interaction decreases IRF3 phosphorylation, which leads to reduced IFN-β production; and (2) nsp13 binds and inhibits TBK1 phosphorylation, resulting in decreased IRF3 activation and IFN-β production (Figure 2F).

SIGNOR-262512

P20936

P09619

2

binding

up-regulates

0.58

The gtpase activating protein (gap) of ras binds only to beta-receptors / we have previously shown that the binding site for gtpase activating protein of ras (rasgap) in the pdgf beta-receptor, tyr771, is phosphorylated to a much lower extent in the heterodimeric configuration of pdgf alpha- and beta-receptors, compared to the pdgf beta-receptor homodimer. / the decreased recruitment of the rasgap to the receptor leads to prolonged activation of the ras/map kinase pathway

SIGNOR-115843

Q15637

Q8TAS1

0

phosphorylation

up-regulates

0.406

Sf1 is phosphorylated on serines 80 and 82 in vitro and in vivo. Kis can phosphorylate sf1f on serine 80 and 82 with a high efficiency that particularly relies on the anchoring of its uhm domain to sf1. Serine phosphorylation of a conserved ser80-pro81-ser82-pro83 motif rigidifies a long unstructured linker in the sf1 helix hairpin and slightly enhances rna binding.

SIGNOR-199797

Q8IXJ9

P19793

2

binding

up-regulates activity

0.284

In this study, we demonstrate that mammalian ASXL1 interacts with the AF-2 AD core of RAR (and RXR) through a novel, promiscuous NR box (LVMQLL) and enhances transcriptional activity of the receptors in certain cells.

SIGNOR-255911

P49841

P03372

1

phosphorylation

up-regulates

0.34

The gsk-3 inhibitor lithium chloride was used to determine the role of gsk-3 in phosphorylation of ser-102, -104, and -106 and ser-118 in vivo and to explore the role of these serines in the regulation of eralpha function. Treatment of cells with lithium chloride resulted in dephosphorylation of ser-104 and -106 and ser-118, which suggests these serine residues as targets for gsk-3 in vivo. Our results further suggest that eralpha phosphorylation by gsk-3 stabilizes eralpha under resting conditions and modulates eralpha transcriptional activity upon ligand binding. Estradiol and phorbol ester cause phosphorylation of serine 118 in the human estrogen receptor. Potentiation of human estrogen receptor alpha transcriptional activation through phosphorylation of serines 104 and 106 by the cyclin a-cdk2 complex.

SIGNOR-139316

P10636

Q9H992

0

ubiquitination

down-regulates activity

0.2

We have identified and characterized axotrophin, a protein that binds and preferentially mono-ubiquitinates tau protein.

SIGNOR-278655

O60825

Q13131

0

phosphorylation

up-regulates activity

0.464

Heart 6-phosphofructo-2-kinase activation by insulin results from ser-466 and ser-483 phosphorylation and requires 3-phosphoinositide-dependent kinase-1, but not protein kinase b.

SIGNOR-84061

P24941

P28324

1

phosphorylation

up-regulates activity

0.363

Phosphorylation of ELK4 at Thr194 and Ser387 by CDK2 is required for EGF-induced cell transformation.

SIGNOR-278210

P55075

P19622

0

transcriptional regulation

down-regulates quantity by repression

0.416

Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression.

SIGNOR-265801

P18075

Q13873

2

binding

up-regulates

0.804

In transfected cos-1 cells, osteogenic protein (op)-1/bmp-7, and less efficiently bmp-4, bound to bmpr-ii. Bmpr-ii bound ligands only weakly alone, but the binding was facilitated by the presence of previously identified type i receptors for bmps. Binding of op-1/bmp-7 to bmpr-ii was also observed in nontransfected cell lines. Moreover, a transcriptional activation signal was transduced by bmpr-ii in the presence of type i receptors after stimulation by op-1/bmp-7.

SIGNOR-30512

Q16665

Q9P0U3

0

desumoylation

up-regulates

0.325

Sumo-specific protease 1 is essential for stabilization of hif1alpha during hypoxia / our results support a model in which sumoylated hif1_ is unstable but can be stabilized when sumo is removed by senp1

SIGNOR-158891

Q9UHD2

Q96CV9

2

phosphorylation

up-regulates activity

0.789

Given that TBK1 can phosphorylate OPTN on S177, S473 and S513 in response to mitochondrial depolarization, we explored the function of these events in vivo.|Phosphorylation of OPTN on S473 and S513 promotes TBK1 activation and recruitment of OPTN to depolarized mitochondria.

SIGNOR-278170

O14737

O14829

0

dephosphorylation

down-regulates quantity by destabilization

0.349

Here, we report that the serine/threonine phosphatase PPEF-1 interacts with and dephosphorylates PDCD5 at Ser 119, which leads to PDCD5 destabilization.|These results demonstrate that PPEF-1 reduces PDCD5 stability via PDCD5 dephosphorylation.

SIGNOR-277008

Q5JWF2

P32245

0

null

up-regulates activity

0.521

We hypothesize that XLŒ±s may be involved in this regulatory loop by coupling to melanocortin receptors 3 and 4 in the hypothalamus.

SIGNOR-253067

Q00535

Q96KR7

1

phosphorylation

down-regulates quantity

0.2

We show that scapinin is phosphorylated at a highly conserved site in the central region of the protein (Ser-277) by Cdk5 in vitro. Expression of a scapinin phospho-mimetic mutant (S277D) restored normal axon elongation without affecting actin binding. Instead, phosphorylated scapinin was sequestered in the cytoplasm of neurons and away from the axon.

SIGNOR-273607

P28482

Q96PH1

1

phosphorylation

up-regulates

0.325

These results suggest that the mek/erk1/2 pathway is necessary but not sufficient to regulate the pma-dependent activation of nox5.

SIGNOR-171847

O60610

P55283

1

null

up-regulates activity

0.2

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-253110

P29317

P29353

2

binding

up-regulates

0.616

We also show that the interaction of epha2 with grb2 is indirect and mediated by shc and that this complex is necessary for epha2-mediated activation of erk kinases.

SIGNOR-94804

Q00987

Q9NQU5

0

phosphorylation

up-regulates activity

0.2

We also showed that PAK6 phosphorylates Mdm2 on Thr-158 and Ser-186, which is critical for AR ubiquitin-mediated degradation.

SIGNOR-276428

Q96JH7

P06493

0

phosphorylation

down-regulates activity

0.537

We clarified that VCIP135, an essential factor in both p97 membrane fusion pathways, is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis and that this phosphorylated VCIP135 does not bind to p97.

SIGNOR-265038

P18848

Q9UGM6

1

transcriptional regulation

up-regulates quantity by expression

0.246

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-269430

Q9Y286

O14543

2

binding

down-regulates quantity by destabilization

0.372

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

SIGNOR-272642

Q9NP71

P25445

1

transcriptional regulation

up-regulates quantity by expression

0.2

The present study provides evidence for a direct and dominant role of ChREBP in the glucose regulation of two key liver lipogenic enzymes, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS)

SIGNOR-267947

P03952

P01042

1

cleavage

up-regulates activity

0.779

Bradykinin is a nonapeptide composed of the sequence Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg and functions as an inflammatory mediator. BK is the product of the kallikrein–kinin system following activation of FXII. FXIIa leads to proteolysis of PK, and the resulting PKa cleaves HK to generate BK (Figure 1).

SIGNOR-263548

P04626

Q02297

2

binding

up-regulates

0.792

Direct interaction between heregulin and the two proteins was demonstrated by chemical cross-linking experiments using 125i-heregulin followed by immunoprecipitation with antibodies specific for erbb2 or erbb3.

SIGNOR-26875

Q8N2W9

P84022

2

binding

down-regulates

0.648

Piasy binds most strongly with smad3 and also associates with other receptor-regulated smads and smad4. smad3, smad4, and piasy can form a ternary complex. Piasy does not inhibit smad complex binding to dna, but it represses smad transcriptional activity.

SIGNOR-104538

P68400

Q13351

1

phosphorylation

up-regulates activity

0.344

Regulation of erythroid Krppel-like factor (EKLF) transcriptional activity by phosphorylation of a protein kinase casein kinase II site within its interaction domain. the transactivation capability of EKLF is augmented by co-transfection of CKIIalpha. in vitro assays demonstrate that CKIIalpha interacts with EKLF, and that the EKLF interaction domain is phosphorylated by CKII only at Thr-41

SIGNOR-241361

P53350

Q13158

1

phosphorylation

down-regulates activity

0.459

Fas-associated death domain-containing protein (FADD) was first identified as an adapter molecule involved in formation of a death-inducing signaling complex upon Fas stimulation| Plk1 phosphorylates fadd at ser-194 in response to treatment with taxol Phosphorylation by polo-like kinase 1 induces the tumor-suppressing activity of FADD

SIGNOR-168204

Q9UQ88

P24522

2

binding

down-regulates activity

0.2

GADD45alpha inhibits CDK11p58 kinase activity|We identified CDK11p58 as an interaction partner of GADD45α by co-immunoprecipitation analysis. We corroborated these data by co-immunoprecipitation in vitro translation assays, showing that all three members of the GADD45 family interact with CDK11p58.

SIGNOR-273023

P05106

Q15118

0

phosphorylation

down-regulates activity

0.306

PDK1 specifically phosphorylates Thr-753 in 3. Our data argue that phosphorylation of Thr-753, which is conserved in many subunits, reduces the ability of PTB-containing proteins to bind the NXX(pY) motif in 3.

SIGNOR-250264

Q96EP1

P51532

1

polyubiquitination

down-regulates quantity by destabilization

0.333

Here we report that CHFR interacts with BRG1, SNF5, and BAF60a of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and that SRG3/mBAF155 stabilizes these components by blocking their interaction with CHFR. These results suggest that CHFR enhances the degradation of the components of the SWI/SNF-like BAF complex by inducing their poly-ubiquitination.

SIGNOR-271457

Q14457

Q13464

0

phosphorylation

up-regulates activity

0.415

Beclin1 is phosphorylated by ROCK1 at T119.

SIGNOR-278198

P06401

Q9Y618

0

acetylation

down-regulates

0.588

In this study we assessed the effect of smrt and dax-1 on ar and pr activity in the presence of both agonists and partial antagonists. We show that smrt and dax-1 repress agonist-dependent activity of both receptors, and the mechanism of repression includes disruption of the receptor dimer interactions rather than recruitment of histone deacetylases.

SIGNOR-101289

P07948

P11912

1

phosphorylation

up-regulates activity

0.738

Y182 of CD79a appears to be the initial and preferred site of Ag receptor phosphorylation by Src family kinases. In vitro, Src family Lyn and Fyn predominantly phosphorylate this residue in CD79a, and Y195 does so in CD79b. phosphorylation of Y182 alone can lead to further kinase activation and/or effector focusing necessary for phosphorylation of certain downstream targets, such as p62, p110, and Shc, but not others, such as Vav.

SIGNOR-251397

P15311

P25098

0

phosphorylation

up-regulates

0.2

Grk2 phosphorylates glutathione s-transferase (gst)-ezrin, but not an ezrin fusion protein lacking threonine 567 (t567), in vitro. These results suggest that t567, the regulatory phosphorylation site responsible for maintaining ezrin in its active conformation, represents the principle site of grk2-mediated phosphorylation.

SIGNOR-135622

Q92585

Q9UM47

2

binding

up-regulates

0.79

Maml1 binds to the ankyrin repeat domain of all four mammalian notch receptors, forms a dna-binding complex with icn and rbp-jkappa, and amplifies notch-induced transcription of hes1.

SIGNOR-84838

Q9UBY8

P67775

2

binding

up-regulates activity

0.2

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

SIGNOR-265583

Q86YS7

P31751

0

phosphorylation

up-regulates activity

0.513

MS analysis of an HA-CDP138 sample from the in vitro kinase assay revealed that active Akt2 induces CDP138 phosphorylation at serine (Ser)197, which lies within a consensus Akt substrate motif RQRLIS 197 ( xref ).

SIGNOR-279585

Q9UQD0

P49841

0

phosphorylation

up-regulates activity

0.2

In vivo genetic manipulations demonstrate that GSK3β and Nav1.6 are molecular determinants of MSN excitability and that silencing of GSK3β prevents maladaptive plasticity of IC MSNs. In vitro studies reveal direct interaction of GSK3β with Nav1.6 and phosphorylation at Nav1.6T1936 by GSK3β. A GSK3β-Nav1.6T1936 competing peptide reduces MSNs excitability in IC, but not EC rats. These results identify GSK3β regulation of Nav1.6 as a biosignature of MSNs maladaptive plasticity.

SIGNOR-275763

P08069

P01344

2

binding

up-regulates activity

0.821

These results strongly suggest that the IGF2–IGF1R–IRS2 axis signals to PI3K in CRC and imply that therapeutic targeting of the pathway could act to block PI3K activity in this subset of patients.

SIGNOR-251495

P19793

P45985

0

phosphorylation

down-regulates

0.2

Phosphorylation by mkk4/sek1 had profound effects on the biochemical properties of rxr, inhibiting the expression of genes activated by rxr-retinoic acid receptor complexes. Tyr-249 in the rxr de region was required for the inhibitory effect of mkk4/sek1.

SIGNOR-80619

Q05513

Q9Y243

1

phosphorylation

up-regulates activity

0.546

Full activation of the PKB enzyme requires phosphorylation of a threonine in the activation

SIGNOR-249153

P07359

P78536

0

cleavage

down-regulates activity

0.284

GPIbα is shed by metalloproteases such as ADAM17, a process that releases a soluble GPIbα fragment termed glycocalicin. ADAM17 cleaves within the GPIbα-based peptide (LRGV465LK) through a mechanism that is only partially understood [42]. GPIbα shedding has been shown to be constitutive but it can be increased by activation of protein kinases C (PKC) or inhibition of calmodulin [42, 43]. Shedding leads to decreased receptor density

SIGNOR-261861

Q9BXY4

O75473

2

binding

up-regulates

0.657

Here we demonstrate that lgr4 and lgr5 bind the r-spondins with high affinity and mediate the potentiation of wnt/betBeta-catenin signaling by enhancing wnt-induced lrp6 phosphorylation

SIGNOR-174535

P01112

P42336

2

binding

up-regulates

0.924

In vivo, dominant negative ras mutant n17 inhibits growth factor induced production of 3' phosphorylated phosphoinositides in pc12 cells, and transfection of ras, but not raf, into cos cells results in a large elevation in the level of these lipids. Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85. it was also described that ras interacts with pi3k in a direct manner. lysine residue 227 is essential for the interaction of ras with pi3k

SIGNOR-35878

O14994

P27361

0

phosphorylation

up-regulates

0.2

A rare, missense polymorphism, s470n, was identified in the synapsin iii gene and appeared more frequently in individuals with schizophrenia than in controls. Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action.

SIGNOR-121402

P56945

Q6P5Z2

2

binding

up-regulates activity

0.2

Taken together, the data suggest that p130Cas expression induces PKN3 activation and this activation is independent of p130Cas–PKN3 interaction.

SIGNOR-264573

Q9H492

Q8IXH6

2

binding

up-regulates

0.408

Tp53inp2 is a scaffold protein that recruits lc3 and/or lc3-related proteins to the autophagosome membrane by interacting with the transmembrane protein vmp1

SIGNOR-182614

Q9H0X6

P08670

1

ubiquitination

down-regulates quantity by destabilization

0.2

Here, we show that RING finger protein 208 (RNF208) decreases the stability of soluble Vimentin protein through a polyubiquitin-mediated proteasomal degradation pathway, thereby suppressing metastasis of TNBC cells

SIGNOR-269051

Q9NP59

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.257

NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. SLC40A1 is a target gene of NFE2L2, with a putative ARE identified approximately -7 kb upstream of the SLC40A1 core promoter.

SIGNOR-279863

O75385

Q9Y2M5

2

binding

down-regulates quantity by destabilization

0.249

Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination. KLHL20 promotes ubiquitination of phagophore-residing VPS34 and Beclin-1

SIGNOR-272413

Q9ULB1

Q8NFZ4

2

binding

up-regulates activity

0.825

The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites.

SIGNOR-265452

P09471

P28336

2

binding

up-regulates activity

0.268

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-257248

P06493

O75154

1

phosphorylation

up-regulates quantity

0.2

FIP3 is phosphorylated on S102 in a cell cycle-dependent manner. We identify four sites of phosphorylation of FIP3 in vivo, S-102, S-280, S-347 and S-450 and identify S-102 as a target for Cdk1-cyclin B in vitro. Of these, we show that S-102 is phosphorylated in metaphase and is dephosphorylated as cells enter telophase.

SIGNOR-273588

P61328

P35499

2

binding

down-regulates activity

0.255

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-253432

Q13049

Q9H9R9

1

ubiquitination

down-regulates quantity by destabilization

0.2

TRIM32 is an E3 ubiquitin ligase for dysbindin. TRIM32 targets dysbindin for degradation.

SIGNOR-271422

Q14940

P68400

0

phosphorylation

down-regulates activity

0.2

CK2 phosphorylation of an acidic Ser/Thr di-isoleucine motif in the Na+/H+ exchanger NHE5 isoform promotes association with beta-arrestin2 and endocytosis

SIGNOR-276250