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
P07384	P20810	2	binding	down-regulates activity	0.915	In addition to Ca2+, calpastatin has a key role in the regulation of calpain. Calpastatin, a heat-stable protein ranging from ~70 to ~140 kDa of apparent molecular weight depending on the cell type, is considered a specific endogenous inhibitor of calpains\|The calpastatin molecule contains four inhibitory units [75–77]. Each of these units binds to one calpain molecule [75–77]. Therefore, the ratio calpain/calpastatin plays a key role in the regulation of calpain activity [78–80]. The inhibitory effect of calpastatin requires Ca2+-dependent high-affinity binding to three sites of calpain	SIGNOR-251582
Q01718	P01189-PRO_0000024969	2	binding	up-regulates activity	0.2	Here, we show that, whereas MRAP was essential for activation of MC2R signaling, MRAP2 was an endogenous inhibitor that competed with MRAP for binding to MC2R and decreased the potency of adrenocorticotropic hormone (ACTH), the endogenous agonist for MC2Rs, in stimulating the production of adenosine 3',5'-monophosphate (cAMP).	SIGNOR-268616
Q92934	P04049	0	phosphorylation	down-regulates	0.66	The activation of several major anti-apoptotic signaling pathways correlates with an increase in the phosphorylation of bad on ser-112, ser-136, and ser-155. These phosphorylation events result in bad inactivation through sequestration by 14-3-3 proteins	SIGNOR-155293
O14713	P16144	2	binding	down-regulates activity	0.349	Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation	SIGNOR-257658
P42771	Q00534	2	binding	down-regulates	0.871	In addition, cytoplasmic p16 bound cyclin dependent kinase (cdk)4/6, potentially indicating that p16 could have a function in the cytoplasm.	SIGNOR-140412
O43683	Q96GD4	0	phosphorylation	up-regulates activity	0.749	Although our analysis identified only one of the 15 sites implicated in Bub1-Mad1 interaction, it suggests that following its rapamycin-induced dimerization, Ipl1 phosphorylates Bub1, and potentially Mad1, to drive eSAC signaling.	SIGNOR-279010
Q6NXT1	Q05655	0	phosphorylation	up-regulates activity	0.2	The mechanism by which phosphorylation of Ankrd54 by PKC\u03b4 enhances cytoplasmic accumulation of Ankrd54 and its interaction with Lyn remains to be determined.\|This revealed, in agreement with the biochemical analysis, that PKCdelta significantly promotes cytoplasmic accumulation of Ankrd54.	SIGNOR-279259
P41594	Q04759	0	phosphorylation	up-regulates activity	0.291	Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.	SIGNOR-249290
Q04206	Q96L73	0	methylation	up-regulates	0.463	Fbxl11 and nsd1 have opposite effects on nf-kb; both bind to p65 subunit after activation of nf-kb. / nsd1 activates nf-kb and reverses the inhibitory effect of fbxl11 / these data confirm that fbxl11 and nsd1 constitute an enzyme pair that methylates and demethylates p65 on k218 and 221 in response to cytokine stimulation.	SIGNOR-163454
O00254	Q15835	0	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-279993
Q92945	P12931	1	post transcriptional regulation	up-regulates quantity by expression	0.271	We show here that this component of the DCS complex is hnRNP H and that, like hnRNP F and KSRP, hnRNP H is needed for src N1 splicing in vitro.	SIGNOR-261274
Q14774	P05412	1	transcriptional regulation	up-regulates quantity by expression	0.2	In this study, we have identified cell cycle regulatory genes as downstream targets of the homeobox gene HLX in cultured trophoblast cells, namely RB1, MYC, EGR1, CDKN1C, ELK1, CCNB1, and JUN. RB1 and MYC mRNA expression was increased with HLX inactivation, whereas EGR1, CDKN1C, ELK1, CCNB1, and JUN mRNA expression was decreased compared with mock-transfected control cells.	SIGNOR-261623
P46531	Q9NR61	2	binding	up-regulates activity	0.644	Expression analysis of known notch ligands suggests that dll4 is the only ligand that exhibits spatial and temporal expression consistent with the activation of notch1 and notch4 during vascular development. The identification of dll4 reveals a candidate ligand for notch receptors involved in blood vessel biology	SIGNOR-112649
P27361	Q8IVS8	1	phosphorylation	up-regulates quantity by stabilization	0.2	Mechanistically, glucose deprivation-activated ERK1 phosphorylates GLYCTK2 at serine 220 directly, which prevents STUB1 (ubiquitin E3 ligase) binding, thereby abrogating the ubiquitination and degradation of GLYCTK2. ERK1 phosphorylates GLYCTK2 at S220 to promotes its stability	SIGNOR-280257
Q15831	P54646	1	phosphorylation	up-regulates	0.627	We demonstrated that lkb1 phosphorylates ampk on the activation loop threonine (thr172) within the catalytic subunit and activates ampk in vitro. Here, we have investigated whether lkb1 corresponds to the major ampkk activity present in cell extracts. Ampkk purified from rat liver corresponds to lkb1, and blocking lkb1 activity in cells abolishes ampk activation in response to different stimuli	SIGNOR-122725
Q9H2X6	P51608	1	phosphorylation	up-regulates activity	0.478	Here, we identify the homeodomain-interacting protein kinase 2 (HIPK2) as a kinase that binds MeCP2 and phosphorylates it at Ser 80 in vitro and in vivo.	SIGNOR-264549
P05556	Q9H158	2	binding	up-regulates activity	0.2	The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion.	SIGNOR-269032
P31269	Q15910	0	transcriptional regulation	down-regulates quantity by repression	0.396	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-260068
P43354	P28702	2	binding	up-regulates	0.417	The recent discovery that the nuclear transcription factor, nurr1, in heterodimeric tandem with rxr, is unequivocally necessary for the expression of dopaminergic neurons	SIGNOR-58309
Q99683	P38936	1	phosphorylation	up-regulates	0.589	P21cip1 is phosphorylated in vitro by both ask1 and jnk1 at s98. /phosphorylation of p21cip1 at s98, which in vivo appears to be regulated by ask1, may therefore mediate negative feedback in the ask1 signaling pathway.	SIGNOR-153440
P48039	P08754	2	binding	up-regulates activity	0.498	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-256849
Q05209	P56945	1	dephosphorylation	down-regulates	0.546	Ptp-pest is an efficient negative regulator of lymphocyte activation. This function correlated with the ability of ptp-pest to induce dephosphorylation of shc, pyk2, fak and cas, and inactivate the ras pathway.	SIGNOR-109032
P45983	Q96J02	1	phosphorylation	up-regulates activity	0.654	Itch undergoes JNK1-mediated phosphorylation that greatly enhances its enzymatic activity. To investigate how phosphorylation activates an E3 Ub ligase we have identified the JNK1 phosphorylation sites within Itch as S199, S232, and T222	SIGNOR-245323
Q15910	Q9Y297	0	ubiquitination	down-regulates	0.376	_-trcp ubiquitinates ezh2 and jak2-mediated phosphorylation on y641 directs _-trcp-mediated ezh2 degradation.	SIGNOR-204481
Q9UHD2	A5D8V6	1	phosphorylation	down-regulates activity	0.366	We have identified that TBK1 may target and phosphorylate VPS37C, a structural component of ESCRT-I complex, and serve as a ratelimiting factor in the control of PTAP-dependent (HIV-1, MLV/p6, and EIAV/PTAP), but not PPPY-dependent (MLV, EIAV/PPPY) retrovirus budding, independent of its role in IFN-I signaling.	SIGNOR-279768
P00533	P25098	1	phosphorylation	up-regulates activity	0.2	Previous studies showed that EGFR activation results in association of GRK2 with the EGFR and subsequent phosphorylation of GRK2 at three tyrosine residues (Tyr 13, -86, and -92), resulting in activation of GRK2.\|We propose that GRK2 activation by EGFR leads to GRK2 phosphorylation of Mst2 at these sites, which, in turn, regulates the Mst2-Nek2A-PP1\u03b3 complex ( xref ).	SIGNOR-279368
O96020	Q969H0	2	binding	down-regulates quantity by destabilization	0.436	Cdk2 (S384) and GSK3 (T380) prime cyclin E for destruction. The hyper-phosphorylated T380/S384 degron has high affinity for monomeric Fbw7α, which engages the remainder of the SCF to initiate cyclin E's ubiquitination by an E2 enzyme	SIGNOR-271642
P35222	P49841	0	phosphorylation	down-regulates activity	0.86	Wnt regulation of beta-catenin degradation is essential for development and carcinogenesis. beta-catenin degradation is initiated upon amino-terminal serine/threonine phosphorylation, which is believed to be performed by glycogen synthase kinase-3 (GSK-3) in complex with tumor suppressor proteins Axin and adnomatous polyposis coli (APC).	SIGNOR-116528
Q00987	P25098	1	ubiquitination	down-regulates quantity by destabilization	0.2	Our findings show that the signals enabling activity of the GRK2/MST2/Nek2A axis for separation also switches on Mdm2 degradation of GRK2 to ensure accurate centrosome dynamics and proper mitotic spindle functionality.\|Our results show now that EGF-induced phosphorylation of GRK2 on S670 is a key event in initiating centrosome separation and also a relevant clue for limiting centrosome separation, as this event simultaneously triggers the Mdm2-dependent ubiquitination and degradation of GRK2 ( xref ).	SIGNOR-278629
P16410	O60674	0	phosphorylation	up-regulates quantity by stabilization	0.445	Janus Kinase 2 (Jak2) was directly associated with a box 1-like motif in the cytoplasmic tail of CTLA-4 molecule. Jak2 phosphorylated Y-165 residue in the cytoplasmic region of CTLA-4. It has been reported that phosphorylation and dephosphorylation of tyrosine residue Y-165 in the cytoplasmic region of CTLA-4 play an important role in its negative signaling and cell surface expression. Some signaling molecules such as Src homology 2 protein tyrosine phosphatase 2 (SHP-2) and the p85 subunit of phosphatidylinositol 3 kinase (PI3 kinase) associate with phosphorylated tyrosine residue Y-165, through Src homology 2 (SH2) domains. On the other hand, the adapter complex proteins, AP-2 and AP-50 interact with the same tyrosine residue when unphosphorylated, resulting in clathrin-mediated endocytosis of CTLA-4 molecules.	SIGNOR-251346
P01135	Q969F2	2	binding	up-regulates quantity by stabilization	0.449	Here, we show that Naked2 is a short-lived protein with a half-life of 60 min caused by its rapid ubiquitin-mediated proteasomal degradation. Overexpression of TGF-alpha stabilizes Naked2 protein in an EGF receptor (EGFR)-independent manner; a physical interaction between the cytoplasmic tail of TGF-alpha and Naked2 is necessary and sufficient for this protection. We have identified a RING finger protein, AO7/RNF25, as a ubiquitin ligase for Naked2, and we have shown that overexpression of TGF-alpha reduces binding of AO7 to Naked2.	SIGNOR-271739
P42685	P46937	1	phosphorylation	down-regulates quantity by destabilization	0.275	Mechanistically, FRK interacted with and phosphorylated YAP on Tyr391/407/444, which recruited the classical E3 ubiquitin ligase Siah1 to catalyze ubiquitination and eventually degradation of YAP.	SIGNOR-275456
P42229	O14508	1	transcriptional regulation	up-regulates quantity by expression	0.668	We have also found SOCS2 and SOCS3 specifically induced in 32D/Flt3-ITD, both of which are STAT3/5 target genes and known negative regulators of receptor signaling	SIGNOR-261547
P10415	Q5S007	0	phosphorylation	up-regulates activity	0.329	Thus, we propose that Thr56 phosphorylation of Bcl-2 by LRRK2 G2019S might be a crucial step of mitochondrial disorder, which initiates the subsequent cellular damage in the context of PD relevant to G2019S.\|We found that LRRK2 G2019S induced loss of the MMP was recovered in both GFP-Bcl-2 and GFP-M-Bcl-2 stable cells (XREF_FIG -lower panel).	SIGNOR-279531
P19474	P34897	1	ubiquitination	down-regulates quantity	0.2	The expression of TRIM21, but not the expression of the ligase-dead (LD) mutant TRIM21 (C16A, C31A and H33W) 36, increased SHMT2 ubiquitylation, which suggests that TRIM21 is the E3 ligase for SHMT2 and that the E3 ligase activity of TRIM21 is required for SHMT2 ubiquitylation.\|We found that the overexpression of TRIM21 increased the degradation of SHMT2 in high glucose conditions by binding more K63-ubiquitin.	SIGNOR-278792
P29323	Q92823	1	phosphorylation	up-regulates activity	0.298	EphB receptors were found to induce phosphorylation of NrCAM on the tyrosine residue within the FIGQY ankyrin binding motif, inhibiting ankyrin recruitment. Furthermore, NrCAM phospho-FIGQY levels in the SC were decreased in EphB1/3 and EphB1/2/3 null mice and increased in mutant mice overexpressing constitutively active EphB2 kinase.	SIGNOR-262863
P27361	Q15256	1	phosphorylation	up-regulates activity	0.67	Specifically, the complex formation between PTP-SL and ERK2 involves an unusual interaction leading to the phosphorylation of PTP-SL by ERK2 at Thr253 and the inactivating dephosphorylation of ERK2 by PTP-SL.	SIGNOR-249477
Q6VVB1	Q86XI6	1	ubiquitination	down-regulates quantity by destabilization	0.398	Here, we show that the laforin-malin complex downregulates PTG-induced glycogen synthesis in FTO2B hepatoma cells through a mechanism involving ubiquitination and degradation of PTG. We show here that laforin and malin play a crucial role in the regulation of glycogen biosynthesis in FTO2B hepatoma cells. In these cells, the laforin–malin complex counteracts the glycogenic effect of PTG because it promotes its ubiquitination and degradation.	SIGNOR-271728
Q01638	P51617	2	binding	up-regulates activity	0.604	As shown in Figure 3D, MyD88, IRAK, IRAK4, and TRAF6 are all recruited to ST2 upon IL-33 stimulation.	SIGNOR-277706
Q5S007	P30048	1	phosphorylation	down-regulates activity	0.413	Here, we show that LRRK2 interacts with human peroxiredoxin 3 (PRDX3), a mitochondrial member of the antioxidant family of thioredoxin (Trx) peroxidases. Importantly, mutations in the LRRK2 kinase domain significantly increased phosphorylation of PRDX3 compared to wild-type. The increase in PRDX3 phosphorylation was associated with decreased peroxidase activity and increased death in LRRK2-expressing but not in LRRK2-depleted or vector-transfected neuronal cells.	SIGNOR-262891
Q76N32	P51955	0	phosphorylation	down-regulates quantity by destabilization	0.251	In this study we show phosphorylation of Cep68 by Nek2 creates a potential phosphodegron that directs Cep68 destruction through the activity of SCF-beta-Trcp.\|Our above results showed that Nek2 promoted mitotic degradation of Cep68.	SIGNOR-279471
P29474	P54760	0	phosphorylation	up-regulates activity	0.311	These results suggest that activation of Eph-B4 with Ephrin-B2/Fc stimulates eNOS phosphorylation in vitro (XREF_FIG), eg, eNOS may be a downstream mediator of Eph-B4 signaling in endothelial cells.	SIGNOR-279172
P07949	Q13322	2	binding	up-regulates	0.543	Grb7 and grb10, likely relay signals emanating from ret to other, as yet, unidentified targets within the cell	SIGNOR-41699
P36507	P37231	2	binding	up-regulates	0.2	The genomic activity of ppargamma is modulated, in addition to ligand binding, by phosphorylation of a serine residue by mapks, such as extracellular signal-regulated protein kinases-1/2 (erk-1/2), or by nucleocytoplasmic compartmentalization through the erk activators mapk kinases-1/2 (mek-1/2). These mapks phosphorylate (in humans) ser 84 in the ppargamma1 and ser 114 in ppargamma2 isoform.	SIGNOR-179393
Q00987	Q16665	1	ubiquitination	down-regulates quantity by destabilization	0.643	We find that p53 promotes Mdm2-mediated ubiquitination and proteasomal degradation of the HIF-1alpha subunit of hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that regulates cellular energy metabolism and angiogenesis in response to oxygen deprivation.	SIGNOR-271385
Q15436	Q9Y6Y8	2	binding	up-regulates activity	0.572	The results showed that the N-terminal region of p125 is important for the interaction with Sec23p. We confirmed the interaction between the two proteins by a yeast two-hybrid assay. Overexpression of p125, like that of mammalian Sec23p, caused disorganization of the endoplasmic reticulum-Golgi intermediate compartment and Golgi apparatus, suggesting its role in the early secretory pathway.	SIGNOR-265307
O75886	P18031	0	dephosphorylation	up-regulates quantity by stabilization	0.472	Together, the results presented here demonstrate that PTP1B can influence RTK signaling in a previously unrecognized manner. We show that PTP1B directly targets STAM2, part of the ESCRT-0 endosomal sorting complex, and we provide the first evidence that tyrosine phosphorylation affects STAM localization and function. This regulatory mechanism could impact signaling downstream of numerous cell surface receptors that are ubiquitinated and recognized by this conserved sorting machinery.	SIGNOR-248406
P17252	Q15672	1	phosphorylation	up-regulates quantity by stabilization	0.2	Because most of these sites were predicted to be phosphorylated by protein kinase C (PKC), we overexpressed PKCα in several cell lines and found that it phosphorylates Twist1 on Ser-144. we observed that PKCα-mediated Twist1 phosphorylation at Ser-144 inhibits Twist1 ubiquitination and consequently stabilizes it.	SIGNOR-277429
Q8IYA7	Q7RTU7	1	transcriptional regulation	up-regulates quantity by expression	0.415	MKX is a meniscus-enriched transcription factor. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2).	SIGNOR-267213
P08754	P14416	2	binding	up-regulates activity	0.557	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-256844
P11309	Q15796	1	phosphorylation	up-regulates activity	0.2	We further showed that PIM1 could interact with and phosphorylate Smad2 or Smad3 in the nucleus to induce transcription factor (ZEB1, ZEB2, Snail1, Snail2 and Twist) expression and EMT.	SIGNOR-279090
Q5XUX0	Q00987	2	binding	down-regulates quantity by destabilization	0.324	FBXO31 serves as the substrate-recognition component of the SKP/Cullin/F-box protein class of E3 ubiquitin ligases and has been shown to direct degradation of pivotal cell-cycle regulatory proteins including cyclin D1 and the p53 antagonist MDM2.	SIGNOR-277380
Q15811	Q96CN9	0	relocalization	up-regulates activity	0.2	GFP-GCC88 was immunoprecipitated by both the short and long form of ITSN-1 but not with FLAG-Rheb (Figure 4A). These data demonstrate that both GCC88 and ITSN-1 are part of a complex. We propose that GCC88 recruits ITSN-1-L to the TGN, which in turn activates Cdc42 at the trans-face of the Golgi (Figure 9A).	SIGNOR-260600
P04406	Q86Y07	0	phosphorylation	up-regulates activity	0.2	Mechanistically, FBXW10 promotes GAPDH polyubiquitination and activation; VRK2-dependent phosphorylation of GAPDH Ser151 residue is critical for GAPDH ubiquitination and activation.	SIGNOR-277840
P36897	P07900	2	binding	up-regulates	0.415	The data in fig. 5 suggest that hsp90 specifically interacts with t?RI And t?RII In vitro and in vivo. Coupled with our data showing that loss of hsp90 function decreases t?R Levels and blocks tgf?-Induced smad2/3 activation and transcription, this result suggests that hsp90 controls tgf? Signaling as an essential component for stabilizing t?Rs.	SIGNOR-179268
P42338	P21860	2	binding	up-regulates	0.521	Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4.	SIGNOR-146864
Q13634	P35222	2	binding	up-regulates activity	0.576	At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin	SIGNOR-265857
P30411	Q05655	0	phosphorylation	down-regulates activity	0.301	In addition, we found a protein kinase C-dependent phosphorylation of Ser(346) that was mutually exclusive with the basal phosphorylation at Ser(348) and therefore may be implicated in differential regulation of B2 receptor activation. Functional analysis of receptor mutants revealed that a low phosphorylation stoichiometry is sufficient to initiate receptor sequestration while a clustered phosphorylation around Ser(346) is necessary for desensitization of the B2 receptor-induced phospholipase C activation.	SIGNOR-249108
P04628	Q92765	2	binding	down-regulates	0.517	We and others demonstrated that fzb-1 blocks wnt-1 and xwnt-8 signaling in xenopus embryos,	SIGNOR-51762
P29992	P34981	2	binding	up-regulates activity	0.485	Binding of TRH to TRH-R1 receptor, which is coupled to Gq/11 protein, activates phospholipase C, mobilizes calcium and activates protein kinase C.	SIGNOR-267201
O14543	P42229	0	transcriptional regulation	up-regulates quantity by expression	0.637	We have also found SOCS2 and SOCS3 specifically induced in 32D/Flt3-ITD, both of which are STAT3/5 target genes and known negative regulators of receptor signaling	SIGNOR-261548
P68431	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265413
Q15672	P31751	0	phosphorylation	up-regulates activity	0.398	AKT2 phosphorylates Twist1 at S42 to enhance Twist1 mediated E-cadherin suppression.	SIGNOR-279137
P22694	P46020	1	phosphorylation	down-regulates activity	0.325	Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.	SIGNOR-267413
Q7Z570	P35638	1	transcriptional regulation	up-regulates quantity by expression	0.2	ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3).	SIGNOR-269464
P21918	P09471	2	binding	up-regulates activity	0.356	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-257244
Q86UR5	Q9UFD9	2	binding	down-regulates activity	0.341	SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.	SIGNOR-264360
P84022	P84022	2	binding	up-regulates activity	0.2	Smad2 and Smad3 form homo-oligomers upon phosphorylation by the constitutively active TGF-beta type I receptor, and this oligomerization does not require Smad4	SIGNOR-217227
Q9Y468	Q12888	2	binding	down-regulates activity	0.404	L3MBTL1, a tumor suppressor with high affinity for H4K20me2, can block 53BP1 binding at DSBs	SIGNOR-262059
O43193	P12872	2	binding	up-regulates	0.77	A heterotrimeric guanosine triphosphate-binding protein (g protein)-coupled receptor for motilin was isolated from human stomach	SIGNOR-68721
P16615	P26678	2	binding	down-regulates activity	0.751	Heart failure can be traced, in part, to alterations in the activity of the sarcoplasmic reticulum Ca2+ pump that are induced by its interactions with phospholamban, a reversible inhibitor.	SIGNOR-252031
P27361	O95644	1	phosphorylation	down-regulates	0.532	We show that jnk, erk, and p38 physically associate with the nfatc n-terminal regulatory domain and can directly phosphorylate functionally important residues involved in regulating nfatc subcellular localization, namely ser(172) and the conserved nfatc ser-pro repeats.	SIGNOR-74564
Q15569	Q15569	2	phosphorylation	up-regulates activity	0.2	Site-directed mutagenesis analyses revealed that Ser-215 within the activation loop of the kinase domain is the site of serine autophosphorylation of TESK1. Replacement of Ser-215 by alanine almost completely abolished serine autophosphorylation and histone H3 kinase activities.	SIGNOR-246667
P00519	Q13535	1	phosphorylation	up-regulates	0.599	C-abl can phosphorylate atr on y291 and y310 and this phosphorylation appears to have a positive role in atr activation under genotoxic stress.	SIGNOR-167632
P08581	P51608	0	post transcriptional regulation	down-regulates quantity by repression	0.27	MeCP2 binding enhances MET expression in the presence of the rs1858830 C allele, but MET transcription is attenuated by RTT-specific mutations in MeCP2	SIGNOR-264683
Q969V1	P30679	2	binding	up-regulates activity	0.435	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257390
P20393	Q13901	2	binding	up-regulates activity	0.314	SUN-CoR is a protein involved in transcriptional repression by nuclear hormone receptors. The C terminus of SUN-CoR interacts with TR and RevErb in vitro and associates with RevErb in cells, SUN-CoR potentiates repression by both receptors in cells, and the N terminus of SUN-CoR contains an intrinsic repression domain.	SIGNOR-241272
Q00534	P14618	1	phosphorylation	down-regulates activity	0.259	Here, using human cancer cells and patient-derived xenografts in mice, we show that the cyclin D3-CDK6 kinase phosphorylates and inhibits the catalytic activity of two key enzymes in the glycolytic pathway, 6-phosphofructokinase and pyruvate kinase M2.	SIGNOR-279158
O14974	O43293	0	phosphorylation	down-regulates activity	0.547	We conclude from our results Par-4 operates through a "padlock" model in which binding of Par-4 to MYPT1 activates MP by blocking access to the inhibitory phosphorylation sites, and inhibitory phosphorylation of MYPT1 by ZIPK requires "unlocking" of Par-4 by phosphorylation and displacement of Par-4 from the MP complex.\|We have also demonstrated that Par-4 is required for agonist induced, ZIPK mediated inhibition of MYPT1 and thus is an important amplifier of inputs to MP.	SIGNOR-279030
P09429	P09630	2	binding	up-regulates activity	0.298	We show that HMG1 interacts with proteins encoded by the HOX gene family by establishing protein-protein contacts between the HMG box domains and the HOX homeodomain. The functional role of these interactions was studied using the transcriptional activity of the human HOXD9 protein as a model. HMG1 enhances, in a dose-dependent fashion, the sequence-specific DNA binding activity in vitro, and the transcriptional activation in a co-transfection assay in vivo, of the HOXD9 protein.	SIGNOR-219937
Q9C0C7	P63167	2	binding	down-regulates	0.551	The beclin 1vps34 complex is tethered to the cytoskeleton through an interaction between the beclin 1interacting protein ambra1 and dynein light chains 1/2.	SIGNOR-168255
Q01726	Q96G30	2	binding	down-regulates activity	0.491	We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression of MC4R and also the signaling of this receptor. we observed a significant decrease in the cell-surface expression of MC4R and MC5R in the presence of MRAP and MRAP2. It is interesting that MRAP and MRAP2 have opposite effects in the modulation of different MCR family members.	SIGNOR-252365
P32121	Q02750	0	phosphorylation	up-regulates activity	0.587	Here, we show that activation of serotonin 5-HT2C receptors, which engage Erk1/2 pathway via a _-arrestin-dependent mechanism, promotes MEK-dependent _-arrestin2 phosphorylation at Thr383	SIGNOR-252027
Q8WZA2	P62834	2	binding	up-regulates quantity	0.794	The SUR1 subunit of KATP channels recruits Epac2 to the plasma membrane where a signaling complex comprised of Epac2, Rap1 and PLC-ε is formed. Rap1 is activated by Epac2, and the activated form of Rap1 binds to and activates PLC-ε.	SIGNOR-278143
O43559	Q16620	0	phosphorylation	up-regulates activity	0.602	The tyrosine phosphoryla tion of FRS2/SNT2 was stimulated dependently on the TrkB activation. to explore the possibility that tyrosine residues 417 and 455 on FRS2/SNT2 function as the binding sites for Shp2, we coexpressed Y417F or Y455F phenylalanine mutants and the Y417/455F double phenylalanine mutant of Myc/Histagged FRS2/SNT2 with TrkB. The active TrkB induced somewhat reduced tyrosine phosphorylation of all of the phenylalanine mutants of FRS2/SNT2 in comparison with tyrosine phosphorylation of the wild type	SIGNOR-250202
Q92963	Q13129	2	binding	up-regulates activity	0.309	Rit and Rin were found to interact with the known Ras binding proteins RalGDS, Rlf, and AF-6/Canoe. These interactions were GTP and effector domain dependent and suggest that RalGDS, Rlf, and AF-6 are Rit and Rin effectors.	SIGNOR-220799
Q9Y446	P12931	0	phosphorylation	up-regulates activity	0.306	We have discovered that reactive oxygen species (ROS) trigger the c-Src kinase-mediated tyrosine (Tyr)-195 phosphorylation of PKP3. This modification is associated with a change in the subcellular distribution of the protein. Specifically, PKP3 bearing phospho-Tyr-195 is released from the desmosomes, suggesting that phospho-Tyr-195 is relevant for the control of desmosome disassembly and function, at least in cells exposed to ROS.	SIGNOR-273807
P51955	Q5FBB7	1	phosphorylation	up-regulates	0.2	Here we show that nek2a phosphorylates human sgo1 and such phosphorylation is essential for faithful chromosome congression in mitosis. phosphorylation sites were mapped to ser(14) and ser(507)	SIGNOR-156882
Q02446	O43186	2	binding	up-regulates activity	0.388	Sp4 directly binds Crx. Sp4 and Sp1 produce much higher levels of transcriptional activation when co-transfected with Crx, they may additionally act by directly increasing the rate of transcriptional initiation by the general transcriptional apparatus through their activation domains.	SIGNOR-225333
O00562	P28482	0	phosphorylation	up-regulates	0.2	Both cdk1 and erk2 induced phosphorylation of the wild-type nir2. Substitution of t794 by alanine reduced the phosphorylation by erk2, whereas the double mutations t794/1223a completely abolished it. The requirement of multiple nir2 phosphorylation sites for plk1 binding may provide a mechanism that sets a threshold for the nir2-plk1 interaction during mitosis.	SIGNOR-124646
P78352	Q12879	1	relocalization	up-regulates activity	0.811	The PDZ domains of PSD-95 and related proteins interact with the COOH-terminal sequences of K+channels and NMDA2 receptors (3). By these interactions, PSD-95 may mediate the clustering of K+ channels and NMDA receptors at synapses.	SIGNOR-264194
O15409	P78509	1	transcriptional regulation	up-regulates quantity by expression	0.365	By interacting with CASK, TBR1 regulates several ASD candidate genes, such as GRIN2B, AUTS2 and RELN—all of which are recurrently mutated in ASD. In areas of the brain with overlapping expression patterns, such as in glutamatergic layer 6 neurons, the TBR1–FOXP2 interaction may result in co-ordinated regulation of common downstream targets.	SIGNOR-266833
P61244	Q16539	0	phosphorylation	down-regulates	0.627	Mxi2 phosphorylates max both in vitro and in vivo. Phosphorylation by mxi2 may affect the ability of max to oligomerize with itself and its partners, bind dna, or regulate gene expression.	SIGNOR-26511
P84022	Q9BZS1	1	null	up-regulates	0.523	The TCR, IL-2R, and TbetaR must all be stimulated to induce Foxp3 + Tregs. Failure to engage any one of these receptors prevents the generation of Foxp3 + Tregs	SIGNOR-254363
P28482	Q96KB5	2	phosphorylation	up-regulates activity	0.283	In the present study, Ser32 was revealed to be a novel phosphorylated site on TOPK that could be activated by ERK2.\|TOPK/PBK is phosphorylated by ERK2 at serine 32, promotes tumorigenesis and is involved in sorafenib resistance in RCC.	SIGNOR-279744
P51617	P51617	2	phosphorylation	up-regulates activity	0.2	In vitro the IRAK-1 activation loop is a good substrate for IRAK-4, and that T387 and S376 are the main sites of phosphorylation by both IRAK-1 and IRAK-4.	SIGNOR-251330
Q13443	P50281	0	cleavage	down-regulates quantity by destabilization	0.341	Here we show that MT1-MMP forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9\|Western blotting using antibodies against ectodomain of ADAM9 detected a fragment (around 26 kDa) of ADAM9 in the conditioned culture medium from cells cotransfected with wild-type MT1-MMP, but not in that with catalytic activity-dead MT1-MMP (Figure 6A, top).	SIGNOR-260301
P27986	P35568	2	binding	up-regulates activity	0.813	Phosphorylated irs then acts as docking site to recruit and activate phosphatidylinositol-3-kinase (pi3k) which phosphorylates membrane phospholipids, generating phosphoinositide-3,4,5-triphosphate (pip3) from phosphoinositide-4,5-biphosphate (pip2).	SIGNOR-175668
Q7L9L4	Q13188	0	phosphorylation	up-regulates	0.817	Mob1, when phosphorylated by MST1/2, binds to the autoinhibitory motif in Lats1/2, which in turn leads to the phosphorylation of the Lats activation loop (Lats1 S909 and Lats2 S872) and thereby an increase of their kinase activity	SIGNOR-201290
O95405	P84022	2	binding	up-regulates activity	0.861	We now identify SARA (for Smad anchor for receptor activation), a FYVE domain protein that interacts directly with Smad2 and Smad3. SARA functions to recruit Smad2 to the TGFbeta receptor by controlling the subcellular localization of Smad2 and by interacting with the TGFbeta receptor complex.	SIGNOR-62874

P07384

P20810

2

binding

down-regulates activity

0.915

In addition to Ca2+, calpastatin has a key role in the regulation of calpain. Calpastatin, a heat-stable protein ranging from ~70 to ~140 kDa of apparent molecular weight depending on the cell type, is considered a specific endogenous inhibitor of calpains|The calpastatin molecule contains four inhibitory units [75–77]. Each of these units binds to one calpain molecule [75–77]. Therefore, the ratio calpain/calpastatin plays a key role in the regulation of calpain activity [78–80]. The inhibitory effect of calpastatin requires Ca2+-dependent high-affinity binding to three sites of calpain

SIGNOR-251582

Q01718

P01189-PRO_0000024969

2

binding

up-regulates activity

0.2

Here, we show that, whereas MRAP was essential for activation of MC2R signaling, MRAP2 was an endogenous inhibitor that competed with MRAP for binding to MC2R and decreased the potency of adrenocorticotropic hormone (ACTH), the endogenous agonist for MC2Rs, in stimulating the production of adenosine 3',5'-monophosphate (cAMP).

SIGNOR-268616

Q92934

P04049

0

phosphorylation

down-regulates

0.66

The activation of several major anti-apoptotic signaling pathways correlates with an increase in the phosphorylation of bad on ser-112, ser-136, and ser-155. These phosphorylation events result in bad inactivation through sequestration by 14-3-3 proteins

SIGNOR-155293

O14713

P16144

2

binding

down-regulates activity

0.349

Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation

SIGNOR-257658

P42771

Q00534

2

binding

down-regulates

0.871

In addition, cytoplasmic p16 bound cyclin dependent kinase (cdk)4/6, potentially indicating that p16 could have a function in the cytoplasm.

SIGNOR-140412

O43683

Q96GD4

0

phosphorylation

up-regulates activity

0.749

Although our analysis identified only one of the 15 sites implicated in Bub1-Mad1 interaction, it suggests that following its rapamycin-induced dimerization, Ipl1 phosphorylates Bub1, and potentially Mad1, to drive eSAC signaling.

SIGNOR-279010

Q6NXT1

Q05655

0

phosphorylation

up-regulates activity

0.2

The mechanism by which phosphorylation of Ankrd54 by PKC\u03b4 enhances cytoplasmic accumulation of Ankrd54 and its interaction with Lyn remains to be determined.|This revealed, in agreement with the biochemical analysis, that PKCdelta significantly promotes cytoplasmic accumulation of Ankrd54.

SIGNOR-279259

P41594

Q04759

0

phosphorylation

up-regulates activity

0.291

Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.

SIGNOR-249290

Q04206

Q96L73

0

methylation

up-regulates

0.463

Fbxl11 and nsd1 have opposite effects on nf-kb; both bind to p65 subunit after activation of nf-kb. / nsd1 activates nf-kb and reverses the inhibitory effect of fbxl11 / these data confirm that fbxl11 and nsd1 constitute an enzyme pair that methylates and demethylates p65 on k218 and 221 in response to cytokine stimulation.

SIGNOR-163454

O00254

Q15835

0

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-279993

Q92945

P12931

1

post transcriptional regulation

up-regulates quantity by expression

0.271

We show here that this component of the DCS complex is hnRNP H and that, like hnRNP F and KSRP, hnRNP H is needed for src N1 splicing in vitro.

SIGNOR-261274

Q14774

P05412

1

transcriptional regulation

up-regulates quantity by expression

0.2

In this study, we have identified cell cycle regulatory genes as downstream targets of the homeobox gene HLX in cultured trophoblast cells, namely RB1, MYC, EGR1, CDKN1C, ELK1, CCNB1, and JUN. RB1 and MYC mRNA expression was increased with HLX inactivation, whereas EGR1, CDKN1C, ELK1, CCNB1, and JUN mRNA expression was decreased compared with mock-transfected control cells.

SIGNOR-261623

P46531

Q9NR61

2

binding

up-regulates activity

0.644

Expression analysis of known notch ligands suggests that dll4 is the only ligand that exhibits spatial and temporal expression consistent with the activation of notch1 and notch4 during vascular development. The identification of dll4 reveals a candidate ligand for notch receptors involved in blood vessel biology

SIGNOR-112649

P27361

Q8IVS8

1

phosphorylation

up-regulates quantity by stabilization

0.2

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

SIGNOR-280257

Q15831

P54646

1

phosphorylation

up-regulates

0.627

We demonstrated that lkb1 phosphorylates ampk on the activation loop threonine (thr172) within the catalytic subunit and activates ampk in vitro. Here, we have investigated whether lkb1 corresponds to the major ampkk activity present in cell extracts. Ampkk purified from rat liver corresponds to lkb1, and blocking lkb1 activity in cells abolishes ampk activation in response to different stimuli

SIGNOR-122725

Q9H2X6

P51608

1

phosphorylation

up-regulates activity

0.478

Here, we identify the homeodomain-interacting protein kinase 2 (HIPK2) as a kinase that binds MeCP2 and phosphorylates it at Ser 80 in vitro and in vivo.

SIGNOR-264549

P05556

Q9H158

2

binding

up-regulates activity

0.2

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

SIGNOR-269032

P31269

Q15910

0

transcriptional regulation

down-regulates quantity by repression

0.396

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-260068

P43354

P28702

2

binding

up-regulates

0.417

The recent discovery that the nuclear transcription factor, nurr1, in heterodimeric tandem with rxr, is unequivocally necessary for the expression of dopaminergic neurons

SIGNOR-58309

Q99683

P38936

1

phosphorylation

up-regulates

0.589

P21cip1 is phosphorylated in vitro by both ask1 and jnk1 at s98. /phosphorylation of p21cip1 at s98, which in vivo appears to be regulated by ask1, may therefore mediate negative feedback in the ask1 signaling pathway.

SIGNOR-153440

P48039

P08754

2

binding

up-regulates activity

0.498

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-256849

Q05209

P56945

1

dephosphorylation

down-regulates

0.546

Ptp-pest is an efficient negative regulator of lymphocyte activation. This function correlated with the ability of ptp-pest to induce dephosphorylation of shc, pyk2, fak and cas, and inactivate the ras pathway.

SIGNOR-109032

P45983

Q96J02

1

phosphorylation

up-regulates activity

0.654

Itch undergoes JNK1-mediated phosphorylation that greatly enhances its enzymatic activity. To investigate how phosphorylation activates an E3 Ub ligase we have identified the JNK1 phosphorylation sites within Itch as S199, S232, and T222

SIGNOR-245323

Q15910

Q9Y297

0

ubiquitination

down-regulates

0.376

_-trcp ubiquitinates ezh2 and jak2-mediated phosphorylation on y641 directs _-trcp-mediated ezh2 degradation.

SIGNOR-204481

Q9UHD2

A5D8V6

1

phosphorylation

down-regulates activity

0.366

We have identified that TBK1 may target and phosphorylate VPS37C, a structural component of ESCRT-I complex, and serve as a ratelimiting factor in the control of PTAP-dependent (HIV-1, MLV/p6, and EIAV/PTAP), but not PPPY-dependent (MLV, EIAV/PPPY) retrovirus budding, independent of its role in IFN-I signaling.

SIGNOR-279768

P00533

P25098

1

phosphorylation

up-regulates activity

0.2

Previous studies showed that EGFR activation results in association of GRK2 with the EGFR and subsequent phosphorylation of GRK2 at three tyrosine residues (Tyr 13, -86, and -92), resulting in activation of GRK2.|We propose that GRK2 activation by EGFR leads to GRK2 phosphorylation of Mst2 at these sites, which, in turn, regulates the Mst2-Nek2A-PP1\u03b3 complex ( xref ).

SIGNOR-279368

O96020

Q969H0

2

binding

down-regulates quantity by destabilization

0.436

Cdk2 (S384) and GSK3 (T380) prime cyclin E for destruction. The hyper-phosphorylated T380/S384 degron has high affinity for monomeric Fbw7α, which engages the remainder of the SCF to initiate cyclin E's ubiquitination by an E2 enzyme

SIGNOR-271642

P35222

P49841

0

phosphorylation

down-regulates activity

0.86

Wnt regulation of beta-catenin degradation is essential for development and carcinogenesis. beta-catenin degradation is initiated upon amino-terminal serine/threonine phosphorylation, which is believed to be performed by glycogen synthase kinase-3 (GSK-3) in complex with tumor suppressor proteins Axin and adnomatous polyposis coli (APC).

SIGNOR-116528

Q00987

P25098

1

ubiquitination

down-regulates quantity by destabilization

0.2

Our findings show that the signals enabling activity of the GRK2/MST2/Nek2A axis for separation also switches on Mdm2 degradation of GRK2 to ensure accurate centrosome dynamics and proper mitotic spindle functionality.|Our results show now that EGF-induced phosphorylation of GRK2 on S670 is a key event in initiating centrosome separation and also a relevant clue for limiting centrosome separation, as this event simultaneously triggers the Mdm2-dependent ubiquitination and degradation of GRK2 ( xref ).

SIGNOR-278629

P16410

O60674

0

phosphorylation

up-regulates quantity by stabilization

0.445

Janus Kinase 2 (Jak2) was directly associated with a box 1-like motif in the cytoplasmic tail of CTLA-4 molecule. Jak2 phosphorylated Y-165 residue in the cytoplasmic region of CTLA-4. It has been reported that phosphorylation and dephosphorylation of tyrosine residue Y-165 in the cytoplasmic region of CTLA-4 play an important role in its negative signaling and cell surface expression. Some signaling molecules such as Src homology 2 protein tyrosine phosphatase 2 (SHP-2) and the p85 subunit of phosphatidylinositol 3 kinase (PI3 kinase) associate with phosphorylated tyrosine residue Y-165, through Src homology 2 (SH2) domains. On the other hand, the adapter complex proteins, AP-2 and AP-50 interact with the same tyrosine residue when unphosphorylated, resulting in clathrin-mediated endocytosis of CTLA-4 molecules.

SIGNOR-251346

P01135

Q969F2

2

binding

up-regulates quantity by stabilization

0.449

Here, we show that Naked2 is a short-lived protein with a half-life of 60 min caused by its rapid ubiquitin-mediated proteasomal degradation. Overexpression of TGF-alpha stabilizes Naked2 protein in an EGF receptor (EGFR)-independent manner; a physical interaction between the cytoplasmic tail of TGF-alpha and Naked2 is necessary and sufficient for this protection. We have identified a RING finger protein, AO7/RNF25, as a ubiquitin ligase for Naked2, and we have shown that overexpression of TGF-alpha reduces binding of AO7 to Naked2.

SIGNOR-271739

P42685

P46937

1

phosphorylation

down-regulates quantity by destabilization

0.275

Mechanistically, FRK interacted with and phosphorylated YAP on Tyr391/407/444, which recruited the classical E3 ubiquitin ligase Siah1 to catalyze ubiquitination and eventually degradation of YAP.

SIGNOR-275456

P42229

O14508

1

transcriptional regulation

up-regulates quantity by expression

0.668

We have also found SOCS2 and SOCS3 specifically induced in 32D/Flt3-ITD, both of which are STAT3/5 target genes and known negative regulators of receptor signaling

SIGNOR-261547

P10415

Q5S007

0

phosphorylation

up-regulates activity

0.329

Thus, we propose that Thr56 phosphorylation of Bcl-2 by LRRK2 G2019S might be a crucial step of mitochondrial disorder, which initiates the subsequent cellular damage in the context of PD relevant to G2019S.|We found that LRRK2 G2019S induced loss of the MMP was recovered in both GFP-Bcl-2 and GFP-M-Bcl-2 stable cells (XREF_FIG -lower panel).

SIGNOR-279531

P19474

P34897

1

ubiquitination

down-regulates quantity

0.2

The expression of TRIM21, but not the expression of the ligase-dead (LD) mutant TRIM21 (C16A, C31A and H33W) 36, increased SHMT2 ubiquitylation, which suggests that TRIM21 is the E3 ligase for SHMT2 and that the E3 ligase activity of TRIM21 is required for SHMT2 ubiquitylation.|We found that the overexpression of TRIM21 increased the degradation of SHMT2 in high glucose conditions by binding more K63-ubiquitin.

SIGNOR-278792

P29323

Q92823

1

phosphorylation

up-regulates activity

0.298

EphB receptors were found to induce phosphorylation of NrCAM on the tyrosine residue within the FIGQY ankyrin binding motif, inhibiting ankyrin recruitment. Furthermore, NrCAM phospho-FIGQY levels in the SC were decreased in EphB1/3 and EphB1/2/3 null mice and increased in mutant mice overexpressing constitutively active EphB2 kinase.

SIGNOR-262863

P27361

Q15256

1

phosphorylation

up-regulates activity

0.67

Specifically, the complex formation between PTP-SL and ERK2 involves an unusual interaction leading to the phosphorylation of PTP-SL by ERK2 at Thr253 and the inactivating dephosphorylation of ERK2 by PTP-SL.

SIGNOR-249477

Q6VVB1

Q86XI6

1

ubiquitination

down-regulates quantity by destabilization

0.398

Here, we show that the laforin-malin complex downregulates PTG-induced glycogen synthesis in FTO2B hepatoma cells through a mechanism involving ubiquitination and degradation of PTG. We show here that laforin and malin play a crucial role in the regulation of glycogen biosynthesis in FTO2B hepatoma cells. In these cells, the laforin–malin complex counteracts the glycogenic effect of PTG because it promotes its ubiquitination and degradation.

SIGNOR-271728

Q01638

P51617

2

binding

up-regulates activity

0.604

As shown in Figure 3D, MyD88, IRAK, IRAK4, and TRAF6 are all recruited to ST2 upon IL-33 stimulation.

SIGNOR-277706

Q5S007

P30048

1

phosphorylation

down-regulates activity

0.413

Here, we show that LRRK2 interacts with human peroxiredoxin 3 (PRDX3), a mitochondrial member of the antioxidant family of thioredoxin (Trx) peroxidases. Importantly, mutations in the LRRK2 kinase domain significantly increased phosphorylation of PRDX3 compared to wild-type. The increase in PRDX3 phosphorylation was associated with decreased peroxidase activity and increased death in LRRK2-expressing but not in LRRK2-depleted or vector-transfected neuronal cells.

SIGNOR-262891

Q76N32

P51955

0

phosphorylation

down-regulates quantity by destabilization

0.251

In this study we show phosphorylation of Cep68 by Nek2 creates a potential phosphodegron that directs Cep68 destruction through the activity of SCF-beta-Trcp.|Our above results showed that Nek2 promoted mitotic degradation of Cep68.

SIGNOR-279471

P29474

P54760

0

phosphorylation

up-regulates activity

0.311

These results suggest that activation of Eph-B4 with Ephrin-B2/Fc stimulates eNOS phosphorylation in vitro (XREF_FIG), eg, eNOS may be a downstream mediator of Eph-B4 signaling in endothelial cells.

SIGNOR-279172

P07949

Q13322

2

binding

up-regulates

0.543

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

SIGNOR-41699

P36507

P37231

2

binding

up-regulates

0.2

The genomic activity of ppargamma is modulated, in addition to ligand binding, by phosphorylation of a serine residue by mapks, such as extracellular signal-regulated protein kinases-1/2 (erk-1/2), or by nucleocytoplasmic compartmentalization through the erk activators mapk kinases-1/2 (mek-1/2). These mapks phosphorylate (in humans) ser 84 in the ppargamma1 and ser 114 in ppargamma2 isoform.

SIGNOR-179393

Q00987

Q16665

1

ubiquitination

down-regulates quantity by destabilization

0.643

We find that p53 promotes Mdm2-mediated ubiquitination and proteasomal degradation of the HIF-1alpha subunit of hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that regulates cellular energy metabolism and angiogenesis in response to oxygen deprivation.

SIGNOR-271385

Q15436

Q9Y6Y8

2

binding

up-regulates activity

0.572

The results showed that the N-terminal region of p125 is important for the interaction with Sec23p. We confirmed the interaction between the two proteins by a yeast two-hybrid assay. Overexpression of p125, like that of mammalian Sec23p, caused disorganization of the endoplasmic reticulum-Golgi intermediate compartment and Golgi apparatus, suggesting its role in the early secretory pathway.

SIGNOR-265307

O75886

P18031

0

dephosphorylation

up-regulates quantity by stabilization

0.472

Together, the results presented here demonstrate that PTP1B can influence RTK signaling in a previously unrecognized manner. We show that PTP1B directly targets STAM2, part of the ESCRT-0 endosomal sorting complex, and we provide the first evidence that tyrosine phosphorylation affects STAM localization and function. This regulatory mechanism could impact signaling downstream of numerous cell surface receptors that are ubiquitinated and recognized by this conserved sorting machinery.

SIGNOR-248406

P17252

Q15672

1

phosphorylation

up-regulates quantity by stabilization

0.2

Because most of these sites were predicted to be phosphorylated by protein kinase C (PKC), we overexpressed PKCα in several cell lines and found that it phosphorylates Twist1 on Ser-144. we observed that PKCα-mediated Twist1 phosphorylation at Ser-144 inhibits Twist1 ubiquitination and consequently stabilizes it.

SIGNOR-277429

Q8IYA7

Q7RTU7

1

transcriptional regulation

up-regulates quantity by expression

0.415

MKX is a meniscus-enriched transcription factor. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2).

SIGNOR-267213

P08754

P14416

2

binding

up-regulates activity

0.557

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-256844

P11309

Q15796

1

phosphorylation

up-regulates activity

0.2

We further showed that PIM1 could interact with and phosphorylate Smad2 or Smad3 in the nucleus to induce transcription factor (ZEB1, ZEB2, Snail1, Snail2 and Twist) expression and EMT.

SIGNOR-279090

Q5XUX0

Q00987

2

binding

down-regulates quantity by destabilization

0.324

FBXO31 serves as the substrate-recognition component of the SKP/Cullin/F-box protein class of E3 ubiquitin ligases and has been shown to direct degradation of pivotal cell-cycle regulatory proteins including cyclin D1 and the p53 antagonist MDM2.

SIGNOR-277380

Q15811

Q96CN9

0

relocalization

up-regulates activity

0.2

GFP-GCC88 was immunoprecipitated by both the short and long form of ITSN-1 but not with FLAG-Rheb (Figure 4A). These data demonstrate that both GCC88 and ITSN-1 are part of a complex. We propose that GCC88 recruits ITSN-1-L to the TGN, which in turn activates Cdc42 at the trans-face of the Golgi (Figure 9A).

SIGNOR-260600

P04406

Q86Y07

0

phosphorylation

up-regulates activity

0.2

Mechanistically, FBXW10 promotes GAPDH polyubiquitination and activation; VRK2-dependent phosphorylation of GAPDH Ser151 residue is critical for GAPDH ubiquitination and activation.

SIGNOR-277840

P36897

P07900

2

binding

up-regulates

0.415

The data in fig. 5 suggest that hsp90 specifically interacts with t?RI And t?RII In vitro and in vivo. Coupled with our data showing that loss of hsp90 function decreases t?R Levels and blocks tgf?-Induced smad2/3 activation and transcription, this result suggests that hsp90 controls tgf? Signaling as an essential component for stabilizing t?Rs.

SIGNOR-179268

P42338

P21860

2

binding

up-regulates

0.521

Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4.

SIGNOR-146864

Q13634

P35222

2

binding

up-regulates activity

0.576

At its C-terminus, cadherin interacts with Î²-catenin, which dynamically associates with Î±-catenin, a direct binding partner of filamentous actin

SIGNOR-265857

P30411

Q05655

0

phosphorylation

down-regulates activity

0.301

In addition, we found a protein kinase C-dependent phosphorylation of Ser(346) that was mutually exclusive with the basal phosphorylation at Ser(348) and therefore may be implicated in differential regulation of B2 receptor activation. Functional analysis of receptor mutants revealed that a low phosphorylation stoichiometry is sufficient to initiate receptor sequestration while a clustered phosphorylation around Ser(346) is necessary for desensitization of the B2 receptor-induced phospholipase C activation.

SIGNOR-249108

P04628

Q92765

2

binding

down-regulates

0.517

We and others demonstrated that fzb-1 blocks wnt-1 and xwnt-8 signaling in xenopus embryos,

SIGNOR-51762

P29992

P34981

2

binding

up-regulates activity

0.485

Binding of TRH to TRH-R1 receptor, which is coupled to Gq/11 protein, activates phospholipase C, mobilizes calcium and activates protein kinase C.

SIGNOR-267201

O14543

P42229

0

transcriptional regulation

up-regulates quantity by expression

0.637

We have also found SOCS2 and SOCS3 specifically induced in 32D/Flt3-ITD, both of which are STAT3/5 target genes and known negative regulators of receptor signaling

SIGNOR-261548

P68431

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265413

Q15672

P31751

0

phosphorylation

up-regulates activity

0.398

AKT2 phosphorylates Twist1 at S42 to enhance Twist1 mediated E-cadherin suppression.

SIGNOR-279137

P22694

P46020

1

phosphorylation

down-regulates activity

0.325

Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.

SIGNOR-267413

Q7Z570

P35638

1

transcriptional regulation

up-regulates quantity by expression

0.2

ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3).

SIGNOR-269464

P21918

P09471

2

binding

up-regulates activity

0.356

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-257244

Q86UR5

Q9UFD9

2

binding

down-regulates activity

0.341

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

SIGNOR-264360

P84022

2

binding

up-regulates activity

0.2

Smad2 and Smad3 form homo-oligomers upon phosphorylation by the constitutively active TGF-beta type I receptor, and this oligomerization does not require Smad4

SIGNOR-217227

Q9Y468

Q12888

2

binding

down-regulates activity

0.404

L3MBTL1, a tumor suppressor with high affinity for H4K20me2, can block 53BP1 binding at DSBs

SIGNOR-262059

O43193

P12872

2

binding

up-regulates

0.77

A heterotrimeric guanosine triphosphate-binding protein (g protein)-coupled receptor for motilin was isolated from human stomach

SIGNOR-68721

P16615

P26678

2

binding

down-regulates activity

0.751

Heart failure can be traced, in part, to alterations in the activity of the sarcoplasmic reticulum Ca2+ pump that are induced by its interactions with phospholamban, a reversible inhibitor.

SIGNOR-252031

P27361

O95644

1

phosphorylation

down-regulates

0.532

We show that jnk, erk, and p38 physically associate with the nfatc n-terminal regulatory domain and can directly phosphorylate functionally important residues involved in regulating nfatc subcellular localization, namely ser(172) and the conserved nfatc ser-pro repeats.

SIGNOR-74564

Q15569

2

phosphorylation

up-regulates activity

0.2

Site-directed mutagenesis analyses revealed that Ser-215 within the activation loop of the kinase domain is the site of serine autophosphorylation of TESK1. Replacement of Ser-215 by alanine almost completely abolished serine autophosphorylation and histone H3 kinase activities.

SIGNOR-246667

P00519

Q13535

1

phosphorylation

up-regulates

0.599

C-abl can phosphorylate atr on y291 and y310 and this phosphorylation appears to have a positive role in atr activation under genotoxic stress.

SIGNOR-167632

P08581

P51608

0

post transcriptional regulation

down-regulates quantity by repression

0.27

MeCP2 binding enhances MET expression in the presence of the rs1858830 C allele, but MET transcription is attenuated by RTT-specific mutations in MeCP2

SIGNOR-264683

Q969V1

P30679

2

binding

up-regulates activity

0.435

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

SIGNOR-257390

P20393

Q13901

2

binding

up-regulates activity

0.314

SUN-CoR is a protein involved in transcriptional repression by nuclear hormone receptors. The C terminus of SUN-CoR interacts with TR and RevErb in vitro and associates with RevErb in cells, SUN-CoR potentiates repression by both receptors in cells, and the N terminus of SUN-CoR contains an intrinsic repression domain.

SIGNOR-241272

Q00534

P14618

1

phosphorylation

down-regulates activity

0.259

Here, using human cancer cells and patient-derived xenografts in mice, we show that the cyclin D3-CDK6 kinase phosphorylates and inhibits the catalytic activity of two key enzymes in the glycolytic pathway, 6-phosphofructokinase and pyruvate kinase M2.

SIGNOR-279158

O14974

O43293

0

phosphorylation

down-regulates activity

0.547

We conclude from our results Par-4 operates through a "padlock" model in which binding of Par-4 to MYPT1 activates MP by blocking access to the inhibitory phosphorylation sites, and inhibitory phosphorylation of MYPT1 by ZIPK requires "unlocking" of Par-4 by phosphorylation and displacement of Par-4 from the MP complex.|We have also demonstrated that Par-4 is required for agonist induced, ZIPK mediated inhibition of MYPT1 and thus is an important amplifier of inputs to MP.

SIGNOR-279030

P09429

P09630

2

binding

up-regulates activity

0.298

We show that HMG1 interacts with proteins encoded by the HOX gene family by establishing protein-protein contacts between the HMG box domains and the HOX homeodomain. The functional role of these interactions was studied using the transcriptional activity of the human HOXD9 protein as a model. HMG1 enhances, in a dose-dependent fashion, the sequence-specific DNA binding activity in vitro, and the transcriptional activation in a co-transfection assay in vivo, of the HOXD9 protein.

SIGNOR-219937

Q9C0C7

P63167

2

binding

down-regulates

0.551

The beclin 1vps34 complex is tethered to the cytoskeleton through an interaction between the beclin 1interacting protein ambra1 and dynein light chains 1/2.

SIGNOR-168255

Q01726

Q96G30

2

binding

down-regulates activity

0.491

We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression of MC4R and also the signaling of this receptor. we observed a significant decrease in the cell-surface expression of MC4R and MC5R in the presence of MRAP and MRAP2. It is interesting that MRAP and MRAP2 have opposite effects in the modulation of different MCR family members.

SIGNOR-252365

P32121

Q02750

0

phosphorylation

up-regulates activity

0.587

Here, we show that activation of serotonin 5-HT2C receptors, which engage Erk1/2 pathway via a _-arrestin-dependent mechanism, promotes MEK-dependent _-arrestin2 phosphorylation at Thr383

SIGNOR-252027

Q8WZA2

P62834

2

binding

up-regulates quantity

0.794

The SUR1 subunit of KATP channels recruits Epac2 to the plasma membrane where a signaling complex comprised of Epac2, Rap1 and PLC-ε is formed. Rap1 is activated by Epac2, and the activated form of Rap1 binds to and activates PLC-ε.

SIGNOR-278143

O43559

Q16620

0

phosphorylation

up-regulates activity

0.602

The tyrosine phosphoryla tion of FRS2/SNT2 was stimulated dependently on the TrkB activation. to explore the possibility that tyrosine residues 417 and 455 on FRS2/SNT2 function as the binding sites for Shp2, we coexpressed Y417F or Y455F phenylalanine mutants and the Y417/455F double phenylalanine mutant of Myc/Histagged FRS2/SNT2 with TrkB. The active TrkB induced somewhat reduced tyrosine phosphorylation of all of the phenylalanine mutants of FRS2/SNT2 in comparison with tyrosine phosphorylation of the wild type

SIGNOR-250202

Q92963

Q13129

2

binding

up-regulates activity

0.309

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

SIGNOR-220799

Q9Y446

P12931

0

phosphorylation

up-regulates activity

0.306

We have discovered that reactive oxygen species (ROS) trigger the c-Src kinase-mediated tyrosine (Tyr)-195 phosphorylation of PKP3. This modification is associated with a change in the subcellular distribution of the protein. Specifically, PKP3 bearing phospho-Tyr-195 is released from the desmosomes, suggesting that phospho-Tyr-195 is relevant for the control of desmosome disassembly and function, at least in cells exposed to ROS.

SIGNOR-273807

P51955

Q5FBB7

1

phosphorylation

up-regulates

0.2

Here we show that nek2a phosphorylates human sgo1 and such phosphorylation is essential for faithful chromosome congression in mitosis. phosphorylation sites were mapped to ser(14) and ser(507)

SIGNOR-156882

Q02446

O43186

2

binding

up-regulates activity

0.388

Sp4 directly binds Crx. Sp4 and Sp1 produce much higher levels of transcriptional activation when co-transfected with Crx, they may additionally act by directly increasing the rate of transcriptional initiation by the general transcriptional apparatus through their activation domains.

SIGNOR-225333

O00562

P28482

0

phosphorylation

up-regulates

0.2

Both cdk1 and erk2 induced phosphorylation of the wild-type nir2. Substitution of t794 by alanine reduced the phosphorylation by erk2, whereas the double mutations t794/1223a completely abolished it. The requirement of multiple nir2 phosphorylation sites for plk1 binding may provide a mechanism that sets a threshold for the nir2-plk1 interaction during mitosis.

SIGNOR-124646

P78352

Q12879

1

relocalization

up-regulates activity

0.811

The PDZ domains of PSD-95 and related proteins interact with the COOH-terminal sequences of K+channels and NMDA2 receptors (3). By these interactions, PSD-95 may mediate the clustering of K+ channels and NMDA receptors at synapses.

SIGNOR-264194

O15409

P78509

1

transcriptional regulation

up-regulates quantity by expression

0.365

By interacting with CASK, TBR1 regulates several ASD candidate genes, such as GRIN2B, AUTS2 and RELN—all of which are recurrently mutated in ASD. In areas of the brain with overlapping expression patterns, such as in glutamatergic layer 6 neurons, the TBR1–FOXP2 interaction may result in co-ordinated regulation of common downstream targets.

SIGNOR-266833

P61244

Q16539

0

phosphorylation

down-regulates

0.627

Mxi2 phosphorylates max both in vitro and in vivo. Phosphorylation by mxi2 may affect the ability of max to oligomerize with itself and its partners, bind dna, or regulate gene expression.

SIGNOR-26511

P84022

Q9BZS1

1

null

up-regulates

0.523

The TCR, IL-2R, and TbetaR must all be stimulated to induce Foxp3 + Tregs. Failure to engage any one of these receptors prevents the generation of Foxp3 + Tregs

SIGNOR-254363

P28482

Q96KB5

2

phosphorylation

up-regulates activity

0.283

In the present study, Ser32 was revealed to be a novel phosphorylated site on TOPK that could be activated by ERK2.|TOPK/PBK is phosphorylated by ERK2 at serine 32, promotes tumorigenesis and is involved in sorafenib resistance in RCC.

SIGNOR-279744

P51617

2

phosphorylation

up-regulates activity

0.2

In vitro the IRAK-1 activation loop is a good substrate for IRAK-4, and that T387 and S376 are the main sites of phosphorylation by both IRAK-1 and IRAK-4.

SIGNOR-251330

Q13443

P50281

0

cleavage

down-regulates quantity by destabilization

0.341

Here we show that MT1-MMP forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9|Western blotting using antibodies against ectodomain of ADAM9 detected a fragment (around 26 kDa) of ADAM9 in the conditioned culture medium from cells cotransfected with wild-type MT1-MMP, but not in that with catalytic activity-dead MT1-MMP (Figure 6A, top).

SIGNOR-260301

P27986

P35568

2

binding

up-regulates activity

0.813

Phosphorylated irs then acts as docking site to recruit and activate phosphatidylinositol-3-kinase (pi3k) which phosphorylates membrane phospholipids, generating phosphoinositide-3,4,5-triphosphate (pip3) from phosphoinositide-4,5-biphosphate (pip2).

SIGNOR-175668

Q7L9L4

Q13188

0

phosphorylation

up-regulates

0.817

Mob1, when phosphorylated by MST1/2, binds to the autoinhibitory motif in Lats1/2, which in turn leads to the phosphorylation of the Lats activation loop (Lats1 S909 and Lats2 S872) and thereby an increase of their kinase activity

SIGNOR-201290

O95405

P84022

2

binding

up-regulates activity

0.861

We now identify SARA (for Smad anchor for receptor activation), a FYVE domain protein that interacts directly with Smad2 and Smad3. SARA functions to recruit Smad2 to the TGFbeta receptor by controlling the subcellular localization of Smad2 and by interacting with the TGFbeta receptor complex.

SIGNOR-62874