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
P06493	P08047	1	phosphorylation	up-regulates	0.463	Moreover, we showed that sp1 is a novel mitotic substrate of cdk1/cyclin b1 and is phosphorylated by it at thr 739 before the onset of mitosis.	SIGNOR-163738
Q12972	P17612	0	phosphorylation	down-regulates activity	0.484	NIPP-1 is the RNA-binding subunit of a major species of protein phosphatase-1 in the nucleus. The purified recombinant protein was a potent (Ki = 9.9 +/- 0.3 pM) and specific inhibitor of protein phosphatase-1 and was stoichiometrically phosphorylated by protein kinases A and CK2. At physiological ionic strength, phosphorylation by these protein kinases drastically decreased the inhibitory potency of free NIPP-1. Sequencing and phosphoamino acid analysis of tryptic phosphopeptides enabled us to identify Ser178 and Ser199 as the phosphorylation sites of protein kinase A	SIGNOR-250033
P11226	O00187	2	binding	up-regulates activity	0.74	The results (Fig. 3A) show that the anti-MBL antibody, in addition to binding MBL captures both MASP-1 and MASP-2\|Our results emphasize the similarity between complement activation through the MBL, or 'MBLectin' pathway of the innate immune system and the classical pathway of complement activation (Fig. 5).	SIGNOR-263415
Q9UJD0	Q96E17	1	relocalization	up-regulates activity	0.26	N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle	SIGNOR-264380
P29350	Q14289	1	dephosphorylation	down-regulates	0.359	Raftk binds constitutively to the protein tyrosine phosphatase shptp1.SHPTP1 Plays a negative role in pyk2/raftk signaling by dephosphorylating raftk on tyr-402, thereby inhibiting the interaction of the sh2 domain of c-src with raftk	SIGNOR-71414
P46934	P37231	1	ubiquitination	up-regulates activity	0.386	First, NEDD4 interacts with and ubiquitinates PPARgamma.\|NEDD4 increases PPARgamma stability through the inhibition of its proteasomal degradation.	SIGNOR-278540
Q9HCE7	P36897	1	polyubiquitination	down-regulates quantity by destabilization	0.694	Here we show that Smurf1, an E3 ubiquitin ligase for bone morphogenetic protein-specific Smads, also interacts with Smad7 and induces Smad7 ubiquitination and translocation into the cytoplasm. In addition, Smurf1 associates with TbetaR-I via Smad7, with subsequent enhancement of turnover of TbetaR-I and Smad7.	SIGNOR-272943
Q9NPG1	P09341	2	binding	up-regulates	0.2	In the non-canonical wnt pathway, frizzled uses galfaq or galfai and gbetagamma dimers to activate phospholipase c (plc), resulting in protein kinase c (pkc) activation and calcium mobilization that regulates the transcription factor nfat, and frizzled also signals through the small gtpases rho and rac to c-jun n-terminal kinase (jnk), which activates the ap1 transcription factor gpcrs signal through four relatively small families of galfa proteins (galfas, galfai/o, galfaq, and galfa12/13), and if fzd receptors are classic gpcrs, they should signal through one of these four galfa families.	SIGNOR-152597
P28482	P15923	1	phosphorylation	down-regulates quantity by destabilization	0.36	Notch-induced degradation requires phosphorylation of E47 by p42/p44 MAP kinases. \|Wild_type E47 but not the Mm mutant reacted to the antibodies, suggesting that E47 is at least phosphorylated at the M2 site (Figure 3A)\|anti_phospho_M2 peptide (SSPSpTPVGSPQG)	SIGNOR-249451
Q05586	P05129	0	phosphorylation	up-regulates activity	0.351	Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms. The results show that PKC alpha phosphorylates preferentially S896 and PKC gamma preferentially S890.	SIGNOR-263176
P24385	Q92769	2	binding	up-regulates	0.469	Cyclin d1 bound hdac in vivo and preferentially physically associated with hdac1, hdac2, hdac3, and hdac5.	SIGNOR-134053
Q9NTX7	O15234	1	ubiquitination	down-regulates quantity by destabilization	0.262	Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.	SIGNOR-263339
Q15256	P17612	0	phosphorylation	down-regulates activity	0.343	The PKA phosphorylation site on PTP-SL was identified as the Ser(231) residue. treatment of COS-7 cells with PKA activators, or overexpression of the Calpha catalytic subunit of PKA, inhibited the cytoplasmic retention of ERK2 and p38alpha by wild-type PTP-SL, but not by a PTP-SL S231A mutant.‚	SIGNOR-250038
P40189	P15018	2	binding	up-regulates	0.79	Stimulation of cells with the interleukin-6 family of cytokines triggers homo- or hetero-dimerization of gp130. The dimerization of gp130 leads to activation of associated cytoplasmic tyrosine kinases and subsequent modification of transcription factors.Some Of these biological activities of il-6 are also often exerted by other cytokines, i.e. Il-11, lif, osm, cntf, and ct-2	SIGNOR-48108
P11309	Q13761	1	phosphorylation	up-regulates quantity	0.353	Inhibition of Pim1 kinase prevents peanut allergy by enhancing Runx3 expression and suppressing T (H) 2 and T (H) 17 T-cell differentiation.\|Pim1 kinase phosphorylates and stabilizes Runx3 and alters its subcellular localization.	SIGNOR-279547
P26358	Q00535	0	phosphorylation	up-regulates	0.358	We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5	SIGNOR-173685
P49841	Q9UI10	2	binding	down-regulates	0.2	Akt also promotes protein synthesis by phosphorylating and inactivating gsk3b, thus releasing the gsk3b-dependent inhibition of the eukariotic translation initiation factor 2b (eif2b).	SIGNOR-175572
Q14344	P21731	2	binding	up-regulates activity	0.574	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-257139
P41732	P14416	2	binding	down-regulates quantity	0.252	Tetraspanin-7 (TSPAN7) is expressed to variable degrees in different tissues, with the highest level in the brain, and multiple mutations in TSPAN7 have been implicated in intellectual disability. Our results showed that TSPAN7 was associated with DRD2 and reduced its surface expression by enhancing DRD2 internalization.Finally, TSPAN7 negatively affects DRD2-mediated signaling.	SIGNOR-265557
Q15118	P31749	2	phosphorylation	up-regulates activity	0.601	Since both AKT-1, AKT-2, and SGK-1 are phosphorylated by PDK-1 and are themselves capable of phosphorylating DAF-16, their direct contact may reflect a temporary, regulatory interaction.\|This demonstrates that functional PDK-1 is required to activate AKT-1, AKT-2, and SGK-1 in vivo.	SIGNOR-278973
Q15554	P55795	0	post transcriptional regulation	down-regulates quantity	0.332	During neuronal differentiation, use of an alternative splice site on the rat telomere repeat-binding factor 2 (TRF2) mRNA generates a short TRF2 protein isoform (TRF2-S) capable of derepressing neuronal genes. However, the RNA-binding proteins (RBPs) controlling this splicing event are unknown. Here, using affinity pull-down analysis, we identified heterogeneous nuclear ribonucleoproteins H1 and H2(HNRNPH) as RBPs specifically capable of interacting with the spliced RNA segment (exon 7) of Trf2 pre-mRNA. HNRNPH proteins prevent the production of the short isoform of Trf2 mRNA, as HNRNPH silencing selectively elevates TRF2-S levels.	SIGNOR-266806
P04114	O60216	0	transcriptional regulation	down-regulates quantity	0.2	The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector.	SIGNOR-259974
P12268	P31749	0	phosphorylation	up-regulates activity	0.386	Further, we have demonstrated an in vivo association of IMPDH and PKB/Akt by co‐immunoprecipitation from COS cells expressing a constitutively active form of PKB/Akt. Finally, we were able to show that this constitutively active PKB/Akt could phosphorylate IMPDH in vitro. Thus, the interplay between PKB/Akt and IMPDH reported here could suggest that PKB/Akt activation leads to IMPDH type II activation which in turn prepares the cell for entry into S phase.	SIGNOR-261262
O43236	P98170	2	binding	down-regulates quantity	0.2	The mitochondrial ARTS protein promotes apoptosis through targeting XIAP.\|Binding of ARTS to XIAP is direct, as recombinant ARTS and XIAP proteins can bind to each other in vitro. ARTS binding to XIAP is specific and related to its pro-apoptotic function, as mutant forms of ARTS (or related septins) that fail to bind XIAP failed to induce apoptosis. ARTS leads to decreased XIAP protein levels and caspase activation. Our data suggest that ARTS induces apoptosis by antagonizing IAPs.	SIGNOR-267671
P17612	Q8N752	1	phosphorylation	up-regulates	0.39	Mutation of either the three pka sites or pka-primed cki sites prevents phosphorylation of ci by cki in vitro and blocks ci cleavage in embryos	SIGNOR-144557
Q9NVI1	Q9NW38	0	ubiquitination	up-regulates activity	0.842	Phosphorylation of FANCD2 and Fanconi anemia core components (broken pink circles) affects the efficiency of, but is not essential for, ID ubiquitination by the FA core complex, together with E1 and UBE2T. Analogously, ubiquitination of FANCD2 (solid orange ovals) is essential for DNA repair, activating the ID complex for chromatin binding	SIGNOR-263266
Q9GZQ8	Q13501	2	binding	up-regulates	0.837	Sqstm1/p62 (named a170 in the mouse;hereafter p62) is the first proposed example of such proteins (bj_?_?Rk_?_?Y et al.,2005). It binds polyubiquitinated protein aggregates via its uba domain and interacts with lc3 on the autophagosome/ this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguishable from p62 inclusion bodies and that p62 is required for their formation.	SIGNOR-184255
Q01954	Q9NRD5	0	relocalization	up-regulates activity	0.307	we found that the PDZ domain-containing protein PICK1 (protein interacting with C kinase) interacts specifically with the C-termini of BNC1 and ASIC. Our studies showing association of recombinant PICK1 with ASIC and BNC1, and the presence of both PICK1 and ASIC in the synaptosomal fraction	SIGNOR-223414
P35462	P08754	2	binding	up-regulates activity	0.455	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-256845
P31751	Q96B36	1	phosphorylation	down-regulates	0.674	Insulin-stimulated phosphorylation of pras40 by akt/pkb suppresses its mtorc1 inhibitory activity.	SIGNOR-153931
Q5SQI0	P68363	1	acetylation	up-regulates quantity by stabilization	0.252	Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.\|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules	SIGNOR-272245
P01270	Q03431	2	binding	up-regulates	0.772	Here we show that binding of pth to its receptor pth1r induced association of lrp6, a coreceptor of wnt, with pth1r. The formation of the ternary complex containing pth, pth1r, and lrp6 promoted rapid phosphorylation of lrp6, which resulted in the recruitment of axin to lrp6, and stabilization of beta-catenin.	SIGNOR-182039
P17181	P05000	2	binding	up-regulates	0.728	Ifn-alpha, ifn-beta, and ifn-omega, induce somewhat different cellular effects but act through a common receptor complex, ifnar, composed of subunits ifnar-1 and ifnar-2.	SIGNOR-105979
Q9Y4C0	P58417	2	binding	up-regulates	0.375	We show that neurexophilins 1 and 3 but not 4 (neurexophilin 2 is not expressed in rodents) bind to a single individual lns domain, the second overall lns domain in all three alpha-neurexins.	SIGNOR-60643
P13807	Q86XI6	2	binding	up-regulates	0.714	In the liver, PTG and PPP1R3B(GL)are expressed at roughly equivalent levels [55], and they jointly promote hepatic glycogen mobilization and storage. PTG overexpression significantly increased glycogen content, mainly due to its ability to promote the redistribution of PP1 and glycogen synthase to glycogen granules, significantly increasing GS activity and glycogen synthesis (Figure 2)	SIGNOR-271734
Q14832	P63092	2	binding	up-regulates activity	0.35	MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.	SIGNOR-264083
Q92831	Q06413	2	binding	up-regulates	0.573	The cofactors grip-1, cbp/p300 and pcaf have hat activity and function as co-activators for mef-2c during myogenesis.	SIGNOR-84032
P62805	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-265376
Q9UQL6	Q9Y463	0	phosphorylation	down-regulates activity	0.372	Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent mannermirk phosphorylates hdac5 at ser-279	SIGNOR-235809
Q13202	Q16539	1	dephosphorylation	down-regulates	0.591	M3/6 (dusp8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of jnk and, to a lesser extent, p38 mapk	SIGNOR-199695
Q9UHC7	Q8N726	1	polyubiquitination	down-regulates quantity by destabilization	0.366	Biochemical analyses confirmed that MKRN1 targets p14ARF for ubiquitination and subsequent proteasome-dependent degradation.The Skp1-Cul1-F-box-protein44 (SCF(FBXO44)) complex ubiquitinates full-length BRCA1 in vitro.	SIGNOR-272036
Q14152	Q9Y6E2	2	binding	up-regulates activity	0.324	BZW2, as an evolutionary highly conserved protein, interacts with eIF2 and eIF3 and promotes ternary complex formation in vitro	SIGNOR-261221
Q13315	Q9H981	1	phosphorylation	down-regulates activity	0.2	These findings indicate that ATM dependent phosphorylation on ARP8-S412 reduces ARP8 INO80 interaction.\|These findings raised the possibility that ATM negatively regulates the interaction of ARP8 with INO80 after etoposide treatment.	SIGNOR-279437
P21860	Q9H4P4	0	polyubiquitination	down-regulates quantity by destabilization	0.691	Nrdp1/FLRF is a ubiquitin ligase promoting ubiquitination and degradation of the epidermal growth factor receptor family member, ErbB3	SIGNOR-272599
P51813	P12931	0	phosphorylation	up-regulates	0.535	Coexpression of v-src and etk led to a transphosphorylation on tyrosine 566 of etk and subsequent autophosphorylation. These events correlated with a substantial increase in the kinase activity of etk.	SIGNOR-75330
Q9NRR5	Q13315	0	phosphorylation	up-regulates activity	0.2	These results suggest that UBQLN4 phosphorylation on S318 is functionally important for its role in the DSB response.>Particularly HRR is dependent on ATM activity (Dietlein et al., 2014). Here, we showed that UBQLN4 is an ATM substrate and that DSB sealing is markedly impaired in UBQLN4-depleted cells. HRR depends on a 5′-3′ DSB end resection, which is initiated by the MRE11 nuclease	SIGNOR-265076
P16104	Q14676	2	binding	up-regulates	0.2	Here, we demonstrate that mammalian mdc1/nfbd1 directly binds to phospho-h2ax (gammah2ax) by specifically interacting with the phosphoepitope at the gammah2ax carboxyl terminus.	SIGNOR-143377
Q02750	Q9UHA4	2	binding	up-regulates	0.615	We analyzed the ability of mp1 to bind to mek1, erk1, and to itself, and the regulation of these interactions. Gel filtration of cell lysates revealed two major mp1 peaks: a broad high molecular weight peak and a 28 kda complex. An mp1 mutant that lost mek1 binding no longer enhanced rasv12-stimulated erk1 activity, and functioned as a dominant negative, consistent with the concept that mp1 function depends on facilitating these oligomerizations.	SIGNOR-130924
Q9UIG0	P16104	1	phosphorylation	up-regulates	0.2	We show that wstf phosphorylates tyr 142 of h2a.x, and that wstf activity has an important role in regulating several events that are critical for the dna damage response	SIGNOR-182831
Q9HCK8	P35716	1	transcriptional regulation	down-regulates quantity	0.2	Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells	SIGNOR-268923
O14920	Q9Y6Q9	1	phosphorylation	up-regulates activity	0.378	We demonstrated the in vitro phosphorylation of SRC-3 by the two catalytic subunits of the IKK complex, IKKα and IKKβ. IKK kinase activity is required for synergistic activation with SRC-3	SIGNOR-251298
P22612	Q92934	1	phosphorylation	down-regulates	0.434	Ser-155 is the major phosphoacceptor site for pka on bad, but that pka also phosphorylates ser-112 and ser-136. Phosphorylated bad appears to be the inactive moiety. These results implicate pkac as the candidate kinase for s112 phosphorylation in vivo.	SIGNOR-81153
P51532	P37275	2	binding	up-regulates	0.404	Zeb1 represses e-cadherin transcription / we reported that brg1 binds to the ntr of zeb1 acting as its co-repressor in the regulation of the e-cadherin promoter.	SIGNOR-165017
Q04206	Q06187	0	phosphorylation	up-regulates activity	0.403	Btk induces the phosphorylation of NF-\u03baB p65 which can be induced by the expression of inflammation cytokines [ ].\|Btk induces the phosphorylation of NF-\u03baB p65 which can be induced by the expression of inflammation cytokines [ xref ].	SIGNOR-280197
P16473	P63092	2	binding	up-regulates activity	0.663	The primary signal transduction pathway for TSH receptor is activation of adenylate cyclase via a Gαs G protein-coupled receptor.	SIGNOR-267136
Q8N4X5	P07949	0	phosphorylation	up-regulates activity	0.33	RET/PTC induced robust tyrosine phosphorylation of XB130, which promoted its subsequent association with the p85alpha subunit of phosphatidylinositol 3-kinase (PI 3-kinase). We identified tyrosine 54 of XB130 as the major target of RET/PTC-mediated phosphorylation and a critical binding site for the SH2 domains of p85alpha.	SIGNOR-263192
Q9NW38	Q9NVI1	1	ubiquitination	up-regulates activity	0.842	Phosphorylation of FANCD2 and Fanconi anemia core components (broken pink circles) affects the efficiency of, but is not essential for, ID ubiquitination by the FA core complex, together with E1 and UBE2T. Analogously, ubiquitination of FANCD2 (solid orange ovals) is essential for DNA repair, activating the ID complex for chromatin binding	SIGNOR-263266
O43164	P31323	1	polyubiquitination	down-regulates quantity by destabilization	0.2	Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits	SIGNOR-271858
Q9C040	P07196	1	ubiquitination	down-regulates quantity by destabilization	0.43	Here, we show that TRIM RING finger protein TRIM2, highly expressed in the nervous system, is an UbcH5a-dependent ubiquitin ligase. We further demonstrate that TRIM2 binds to neurofilament light subunit (NF-L) and regulates NF-L ubiquitination.	SIGNOR-271776
Q14289	Q02535	1	phosphorylation	up-regulates quantity	0.2	Taken together these findings demonstrated that Pyk2 mediates the expression of ID3 protein.\|Together these findings from the combined MS+MS/MS data confirm that Flag tagged ID3 is phosphorylated by active recombinant Pyk2 kinase; and support the phospho-Tyr band that was detected at the corresponding MW ~ 13 kDA for Flag-ID3 by immunoblot.	SIGNOR-278496
P55347	P40424	2	binding	up-regulates activity	0.745	we show that Pbx proteins exist as stable heterodimers with a novel homeodomain protein, Prep1. Here we show that Prep1-Pbx interaction presents novel structural features: it is independent of DNA binding and of the integrity of their respective homeodomains, and requires sequences in the N-terminal portions of both proteins. The Prep1-Pbx protein-protein interaction is essential for DNA-binding activity.	SIGNOR-241212
P49715	P22415	2	binding	up-regulates activity	0.317	Our studies show that the human C/EBPa protein stimulates USF to bind to a USF consensus element within C/EBPa promoter and activates it by two- to threefold.The mechanism by which C/EBPa enhances USF binding and transactivation is currently under study.	SIGNOR-255701
Q5T9L3	P56704	1	relocalization	up-regulates activity	0.641	WNT secretion requires its binding to the carrier protein wntless (WLS);	SIGNOR-256599
Q00535	Q05682	1	phosphorylation	down-regulates quantity by destabilization	0.341	Together, these data demonstrate that phosphorylation of caldesmon on Ser527 by Cdk5 serves to down regulate its stability.	SIGNOR-280215
Q9Y271	P50148	2	binding	up-regulates activity	0.385	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257019
Q15796	P16220	2	binding	up-regulates	0.325	We demonstrate that human smad2 and smad4, two essential smad proteins involved in mediating tgf-beta transcriptional responses in endothelial and other cell types, can functionally interact with the transcriptional coactivator creb binding protein (cbp). This interaction is specific in that it requires ligand (tgf-beta) activation and is mediated by the transcriptional activation domains of the smad proteins.	SIGNOR-59462
P42574	Q9NR09	2	binding	down-regulates	0.464	Bruce binds and thereby inhibits caspases, in particular effector caspase-3.	SIGNOR-125956
Q7Z419	P06748	1	ubiquitination	down-regulates quantity by destabilization	0.2	NPMc degradation was mediated by the ubiquitin-proteasome pathway involving the IBR-type RING-finger E3 ubiquitin ligase IBRDC2, and genetic correction of FA-A or FA-C lymphoblasts prevented NPMc ubiquitination. As shown in Fig. 4C, knockdown of IBRDC2, an IBR-type RING-finger E3 ubiquitin ligase (21), significantly reduced NPMc ubiquitination and restored NPMc stability in FA-A cells	SIGNOR-271490
Q6A1A2	O00141	1	phosphorylation	up-regulates	0.2	Our results are consistent with a model in which activation of sgk by igf-1 or hydrogen peroxide is initiated by a ptdins(3,4, 5)p3-dependent activation of pdk2, which phosphorylates ser422.	SIGNOR-66234
Q9NPA2	P08253	1	cleavage	up-regulates activity	0.375	Direct activation of pro-matrix metalloproteinase-2 by leukolysin/membrane-type 6 matrix metalloproteinase/matrix metalloproteinase 25 at the asn(109)-Tyr bond. Leukolysin Cleaves ProMMP-2 at Asn66-Leu and Asn109-Tyr.	SIGNOR-256345
Q9HCE7	Q92519	1	ubiquitination	down-regulates quantity by destabilization	0.41	In this study, we found that TRIB2 was up-regulated and exhibited high stability in liver cancer cells compared with other cells. We performed a structure-function analysis of TRIB2 and identified a domain (amino acids 1-5) at the N terminus that interacted with the E3 ubiquitin ligase Smurf1 and was critical for protein stability. Deletion of this domain extended TRIB2 half-life time accompanied with a more significant malignant property compared with wild type TRIB2.	SIGNOR-275432
Q9BY11	Q9NQU5	0	phosphorylation	up-regulates activity	0.2	We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo.	SIGNOR-263021
Q96HP0	P67775	0	phosphorylation	down-regulates activity	0.2	Akt and PP2A reciprocally regulate the guanine nucleotide exchange factor Dock6 to control axon growth of sensory neurons\|At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser(1194). \| In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, whereas reintroduction of Dock6 with a phosphomimetic S1194E mutation resulted in premature branching	SIGNOR-275669
P36873	P42575	1	dephosphorylation	up-regulates activity	0.2	nutrient-replete oocytes inhibit C2 via S135 phosphorylation catalyzed by calcium/calmodulin-dependent protein kinase II. We now show that C2 phosphorylated at S135 binds 14-3-3zeta, thus preventing C2 dephosphorylation. Moreover, we determined that S135 dephosphorylation is catalyzed by protein phosphatase-1 (PP1), which directly binds C2.	SIGNOR-248503
P25963	P18031	0	dephosphorylation	down-regulates	0.354	Ptp1b is able to dephosphorylate phosphorylated-tyr-42 on ikappabalpha	SIGNOR-45004
P30307	P27348	0	relocalization	down-regulates	0.575	Cdc25c: nuclear exclusion/cytoplasmic sequestration via binding to 14-3-3 proteins.	SIGNOR-163237
Q12778	O15021	0	phosphorylation	down-regulates activity	0.334	MAST4 phosphorylation of FOXO1 regulates RTKN2 expression.	SIGNOR-279079
P28702	P13631	2	binding	up-regulates	0.714	Here we report that the transcriptional activity of rar and rxr can be reciprocally modulated by direct interactions between the two proteins.	SIGNOR-16683
Q92997	Q9UP38	2	binding	up-regulates activity	0.657	Upon ligand binding, DVL proteins are recruited to Frizzled receptors at the plasma membrane and co-recruit cytoplasmic transducers, such as Axin, CK1 and GSK3 binding protein (GBP), presumably along with their partners, to promote ?-catenin-dependent signalling.	SIGNOR-258953
P16220	P98177	2	binding	down-regulates activity	0.308	We provide evidence that the acetyltransferase creb-binding protein (cbp) binds foxo resulting in acetylation of foxo. This acetylation inhibits foxo transcriptional activity	SIGNOR-124711
Q13153	Q16584	0	phosphorylation	up-regulates activity	0.304	Although, MLK3 can phosphorylate PAK1 on Ser133 and Ser204 sites, PAK1S133A mutant is constitutively active, whereas, PAK1S204A is not activated by MLK3.\|MLK3 was able to directly phosphorylate PAK1 on two Serine residues of which Ser204 is critical for MLK3-induced PAK1 activation and downstream functions.	SIGNOR-279418
P22681	P62993	0	relocalization	up-regulates	0.904	The underlying mechanism seems to involve recruitment of a grb2 c-cbl complex to grb2-specific docking sites of egfr, and concurrent acceleration of receptor ubiquitylation and desensitization.	SIGNOR-114704
P51955	Q9NZQ7	1	phosphorylation	up-regulates quantity by stabilization	0.2	NEK2 interacts with PD-L1, phosphorylating the T194/T210 residues and preventing ubiquitin-proteasome pathway-mediated degradation of PD-L1 in ER lumen.	SIGNOR-277314
O60346	P31751	1	dephosphorylation	down-regulates activity	0.621	The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.\|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells.	SIGNOR-248328
Q9NYA1	Q96S38	2	binding	up-regulates activity	0.384	The PSK2 domain of RPK118 is required for binding to SPHK1 as demonstrated by the results from immunoprecipitation analyses (Fig. 6) as well as yeast two-hybrid screening (Fig. 1A). The overexpression of RPK118 in COS7 cells did not cause any change in the intracellular content of SPP with repeated experiments, and RPK118 binding to SPHK1 did not alter the enzymatic activity of SPHK1 in vitro (data not shown), suggesting that RPK118 may function only as an adaptor molecule for SPHK1	SIGNOR-273744
Q96BN8	P0CG48	1	cleavage	up-regulates quantity	0.717	Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.	SIGNOR-270820
P01303	P50391	2	binding	up-regulates	0.692	Human y4 bound human pp family members in i-pyy membrane binding assays with a distinctive rank order (table 1): pp > pyy > npy > npy free acid.	SIGNOR-29633
P08238	Q9P278	2	binding	down-regulates activity	0.263	FNIP1 and FNIP2 facilitate FLCN binding to Hsp90 chaperone. Our results suggest that FNIP1 is a potent inhibitor of Hsp90 ATPase activity, as 200 nM of FNIP1 inhibits Hsp90 ATPase activity by 50-fold. FNIP2 also has shown inhibitory activity towards Hsp90; however, it required 1.6 μM of FNIP2 to inhibit the ATPase activity by eightfold. Although we use the term ‘inhibition' here, FNIPs seem only to be slowing the chaperone cycle.	SIGNOR-261416
P53350	Q8IWB6	1	phosphorylation	down-regulates quantity by destabilization	0.354	We show that phosphorylation of Tex14 by Plk1 during metaphase is required for proteosome dependent degradation of Tex14 and transition from metaphase to anaphase. Phosphorylation of Tex14 Ser431 by Plk1 promotes Tex14 depletion.	SIGNOR-273529
Q9UQM7	P48058	1	phosphorylation	up-regulates	0.592	Receptor internalization, altered;intracellular localization	SIGNOR-97546
P68400	P60484	1	phosphorylation	down-regulates activity	0.68	The C-terminal tail of PTEN is also the target of mutations in tumors. As mentioned, this region contains the main phosphorylation sites mapped to residues Ser362, Thr366, Ser370, Ser380, Thr382, Thr383, and Ser385, and the kinases involved are casein kinase 2 (CK2), GSK3_, LKB1, and MAST.84,97-101 The phosphorylation of the tail has been shown to enhance PTEN stability but at the same time decrease its phosphatase activity	SIGNOR-89830
O75925	Q99608	2	binding	down-regulates quantity by destabilization	0.297	Necdin bound to PIAS1 central domains that are highly conserved among PIAS family proteins and suppressed PIAS1-dependent sumoylation of the substrates STAT1 and PML (promyelocytic leukemia protein). Remarkably, necdin promoted degradation of PIAS1 via the ubiquitin-proteasome pathway. In transfected HEK293A cells, amino- and carboxyl-terminally truncated mutants of PIAS1 bound to necdin but failed to undergo necdin-dependent ubiquitination.	SIGNOR-253387
Q9Y5X5	P08754	2	binding	up-regulates activity	0.25	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256852
P63092	P16473	2	binding	up-regulates activity	0.663	The primary signal transduction pathway for TSH receptor is activation of adenylate cyclase via a Gαs G protein-coupled receptor.	SIGNOR-267136
Q9GZX6	Q8N6P7	2	binding	up-regulates	0.893	In addition, il-22 mediates inflammation and binds class ii cytokine receptor heterodimers il-22 ra1/crf2-4.	SIGNOR-86340
P27169	Q12772	0	transcriptional regulation	up-regulates quantity by expression	0.297	we conclude that quercetin exhibits its antiatherogenic property by eliciting the translocation of the mature SREBP2 from endoplasmic reticulum to the nucleus, where it binds to SRE-like sequence in the PON1 promoter and up-regulates PON1 gene transcription and PON1 activity.	SIGNOR-255224
Q92542	Q96BI3	2	binding	up-regulates	0.967	We show that mammalian aph-1 (maph-1), a conserved multipass membrane protein, physically associates with nicastrin and the heterodimers of the presenilin amino- and carboxyl-terminal fragments in human cell lines and in rat brain. Similar to the loss of presenilin or nicastrin, the inactivation of endogenous maph-1 using small interfering rnas results in the decrease of presenilin levels, accumulation of gamma-secretase substrates (app carboxyl-terminal fragments), and reduction of gamma-secretase products (amyloid-beta peptides and the intracellular domains of app and notch).	SIGNOR-103611
Q96JC1	Q13485	1	relocalization	down-regulates activity	0.318	The data demonstrating binding of TLP to TGF-β and activin type II receptors and selective inhibition of Smad3/Smad4 complex formation by deregulated TLP suggest that TLP is involved in localizing these receptors and Smad4 to specific intracellular compartments, where it regulates formation of Smad3/Smad4 but not Smad2/Smad4 complexes.	SIGNOR-261377
P12004	P00533	0	phosphorylation	up-regulates	0.341	Here, we show that the chromatin-bound pcna protein is phosphorylated on tyr 211, which is required for maintaining its function on chromatin and is dependent on the tyrosine kinase activity of egf receptor (egfr) in the nucleus. Phosphorylation on tyr 211 by egfr stabilizes chromatin-bound pcna protein and associated functions.	SIGNOR-150852
P42338	Q6ZUJ8	2	binding	up-regulates	0.418	This accumulation of tyrosine-phosphorylated bcap at the membrane with its associated pi3k would then allow for the catalysis of ptd ins p2 to ptd ins p3 and downstream pi3k-dependent signals. Therefore, bcap is an essential activator of the pi3k pathway downstream of tlr signaling, providing a brake to limit potentially pathogenic excessive tlr responses.	SIGNOR-191667

P06493

P08047

1

phosphorylation

up-regulates

0.463

Moreover, we showed that sp1 is a novel mitotic substrate of cdk1/cyclin b1 and is phosphorylated by it at thr 739 before the onset of mitosis.

SIGNOR-163738

Q12972

P17612

0

phosphorylation

down-regulates activity

0.484

NIPP-1 is the RNA-binding subunit of a major species of protein phosphatase-1 in the nucleus. The purified recombinant protein was a potent (Ki = 9.9 +/- 0.3 pM) and specific inhibitor of protein phosphatase-1 and was stoichiometrically phosphorylated by protein kinases A and CK2. At physiological ionic strength, phosphorylation by these protein kinases drastically decreased the inhibitory potency of free NIPP-1. Sequencing and phosphoamino acid analysis of tryptic phosphopeptides enabled us to identify Ser178 and Ser199 as the phosphorylation sites of protein kinase A

SIGNOR-250033

P11226

O00187

2

binding

up-regulates activity

0.74

The results (Fig. 3A) show that the anti-MBL antibody, in addition to binding MBL captures both MASP-1 and MASP-2|Our results emphasize the similarity between complement activation through the MBL, or 'MBLectin' pathway of the innate immune system and the classical pathway of complement activation (Fig. 5).

SIGNOR-263415

Q9UJD0

Q96E17

1

relocalization

up-regulates activity

0.26

N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle

SIGNOR-264380

P29350

Q14289

1

dephosphorylation

down-regulates

0.359

Raftk binds constitutively to the protein tyrosine phosphatase shptp1.SHPTP1 Plays a negative role in pyk2/raftk signaling by dephosphorylating raftk on tyr-402, thereby inhibiting the interaction of the sh2 domain of c-src with raftk

SIGNOR-71414

P46934

P37231

1

ubiquitination

up-regulates activity

0.386

First, NEDD4 interacts with and ubiquitinates PPARgamma.|NEDD4 increases PPARgamma stability through the inhibition of its proteasomal degradation.

SIGNOR-278540

Q9HCE7

P36897

1

polyubiquitination

down-regulates quantity by destabilization

0.694

Here we show that Smurf1, an E3 ubiquitin ligase for bone morphogenetic protein-specific Smads, also interacts with Smad7 and induces Smad7 ubiquitination and translocation into the cytoplasm. In addition, Smurf1 associates with TbetaR-I via Smad7, with subsequent enhancement of turnover of TbetaR-I and Smad7.

SIGNOR-272943

Q9NPG1

P09341

2

binding

up-regulates

0.2

In the non-canonical wnt pathway, frizzled uses galfaq or galfai and gbetagamma dimers to activate phospholipase c (plc), resulting in protein kinase c (pkc) activation and calcium mobilization that regulates the transcription factor nfat, and frizzled also signals through the small gtpases rho and rac to c-jun n-terminal kinase (jnk), which activates the ap1 transcription factor gpcrs signal through four relatively small families of galfa proteins (galfas, galfai/o, galfaq, and galfa12/13), and if fzd receptors are classic gpcrs, they should signal through one of these four galfa families.

SIGNOR-152597

P28482

P15923

1

phosphorylation

down-regulates quantity by destabilization

0.36

Notch-induced degradation requires phosphorylation of E47 by p42/p44 MAP kinases. |Wild_type E47 but not the Mm mutant reacted to the antibodies, suggesting that E47 is at least phosphorylated at the M2 site (Figure 3A)|anti_phospho_M2 peptide (SSPSpTPVGSPQG)

SIGNOR-249451

Q05586

P05129

0

phosphorylation

up-regulates activity

0.351

Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms. The results show that PKC alpha phosphorylates preferentially S896 and PKC gamma preferentially S890.

SIGNOR-263176

P24385

Q92769

2

binding

up-regulates

0.469

Cyclin d1 bound hdac in vivo and preferentially physically associated with hdac1, hdac2, hdac3, and hdac5.

SIGNOR-134053

Q9NTX7

O15234

1

ubiquitination

down-regulates quantity by destabilization

0.262

Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.

SIGNOR-263339

Q15256

P17612

0

phosphorylation

down-regulates activity

0.343

The PKA phosphorylation site on PTP-SL was identified as the Ser(231) residue. treatment of COS-7 cells with PKA activators, or overexpression of the Calpha catalytic subunit of PKA, inhibited the cytoplasmic retention of ERK2 and p38alpha by wild-type PTP-SL, but not by a PTP-SL S231A mutant.‚

SIGNOR-250038

P40189

P15018

2

binding

up-regulates

0.79

Stimulation of cells with the interleukin-6 family of cytokines triggers homo- or hetero-dimerization of gp130. The dimerization of gp130 leads to activation of associated cytoplasmic tyrosine kinases and subsequent modification of transcription factors.Some Of these biological activities of il-6 are also often exerted by other cytokines, i.e. Il-11, lif, osm, cntf, and ct-2

SIGNOR-48108

P11309

Q13761

1

phosphorylation

up-regulates quantity

0.353

Inhibition of Pim1 kinase prevents peanut allergy by enhancing Runx3 expression and suppressing T (H) 2 and T (H) 17 T-cell differentiation.|Pim1 kinase phosphorylates and stabilizes Runx3 and alters its subcellular localization.

SIGNOR-279547

P26358

Q00535

0

phosphorylation

up-regulates

0.358

We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5

SIGNOR-173685

P49841

Q9UI10

2

binding

down-regulates

0.2

Akt also promotes protein synthesis by phosphorylating and inactivating gsk3b, thus releasing the gsk3b-dependent inhibition of the eukariotic translation initiation factor 2b (eif2b).

SIGNOR-175572

Q14344

P21731

2

binding

up-regulates activity

0.574

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-257139

P41732

P14416

2

binding

down-regulates quantity

0.252

Tetraspanin-7 (TSPAN7) is expressed to variable degrees in different tissues, with the highest level in the brain, and multiple mutations in TSPAN7 have been implicated in intellectual disability. Our results showed that TSPAN7 was associated with DRD2 and reduced its surface expression by enhancing DRD2 internalization.Finally, TSPAN7 negatively affects DRD2-mediated signaling.

SIGNOR-265557

Q15118

P31749

2

phosphorylation

up-regulates activity

0.601

Since both AKT-1, AKT-2, and SGK-1 are phosphorylated by PDK-1 and are themselves capable of phosphorylating DAF-16, their direct contact may reflect a temporary, regulatory interaction.|This demonstrates that functional PDK-1 is required to activate AKT-1, AKT-2, and SGK-1 in vivo.

SIGNOR-278973

Q15554

P55795

0

post transcriptional regulation

down-regulates quantity

0.332

During neuronal differentiation, use of an alternative splice site on the rat telomere repeat-binding factor 2 (TRF2) mRNA generates a short TRF2 protein isoform (TRF2-S) capable of derepressing neuronal genes. However, the RNA-binding proteins (RBPs) controlling this splicing event are unknown. Here, using affinity pull-down analysis, we identified heterogeneous nuclear ribonucleoproteins H1 and H2(HNRNPH) as RBPs specifically capable of interacting with the spliced RNA segment (exon 7) of Trf2 pre-mRNA. HNRNPH proteins prevent the production of the short isoform of Trf2 mRNA, as HNRNPH silencing selectively elevates TRF2-S levels.

SIGNOR-266806

P04114

O60216

0

transcriptional regulation

down-regulates quantity

0.2

The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector.

SIGNOR-259974

P12268

P31749

0

phosphorylation

up-regulates activity

0.386

Further, we have demonstrated an in vivo association of IMPDH and PKB/Akt by co‐immunoprecipitation from COS cells expressing a constitutively active form of PKB/Akt. Finally, we were able to show that this constitutively active PKB/Akt could phosphorylate IMPDH in vitro. Thus, the interplay between PKB/Akt and IMPDH reported here could suggest that PKB/Akt activation leads to IMPDH type II activation which in turn prepares the cell for entry into S phase.

SIGNOR-261262

O43236

P98170

2

binding

down-regulates quantity

0.2

The mitochondrial ARTS protein promotes apoptosis through targeting XIAP.|Binding of ARTS to XIAP is direct, as recombinant ARTS and XIAP proteins can bind to each other in vitro. ARTS binding to XIAP is specific and related to its pro-apoptotic function, as mutant forms of ARTS (or related septins) that fail to bind XIAP failed to induce apoptosis. ARTS leads to decreased XIAP protein levels and caspase activation. Our data suggest that ARTS induces apoptosis by antagonizing IAPs.

SIGNOR-267671

P17612

Q8N752

1

phosphorylation

up-regulates

0.39

Mutation of either the three pka sites or pka-primed cki sites prevents phosphorylation of ci by cki in vitro and blocks ci cleavage in embryos

SIGNOR-144557

Q9NVI1

Q9NW38

0

ubiquitination

up-regulates activity

0.842

Phosphorylation of FANCD2 and Fanconi anemia core components (broken pink circles) affects the efficiency of, but is not essential for, ID ubiquitination by the FA core complex, together with E1 and UBE2T. Analogously, ubiquitination of FANCD2 (solid orange ovals) is essential for DNA repair, activating the ID complex for chromatin binding

SIGNOR-263266

Q9GZQ8

Q13501

2

binding

up-regulates

0.837

Sqstm1/p62 (named a170 in the mouse;hereafter p62) is the first proposed example of such proteins (bj_?_?Rk_?_?Y et al.,2005). It binds polyubiquitinated protein aggregates via its uba domain and interacts with lc3 on the autophagosome/ this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguishable from p62 inclusion bodies and that p62 is required for their formation.

SIGNOR-184255

Q01954

Q9NRD5

0

relocalization

up-regulates activity

0.307

we found that the PDZ domain-containing protein PICK1 (protein interacting with C kinase) interacts specifically with the C-termini of BNC1 and ASIC. Our studies showing association of recombinant PICK1 with ASIC and BNC1, and the presence of both PICK1 and ASIC in the synaptosomal fraction

SIGNOR-223414

P35462

P08754

2

binding

up-regulates activity

0.455

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-256845

P31751

Q96B36

1

phosphorylation

down-regulates

0.674

Insulin-stimulated phosphorylation of pras40 by akt/pkb suppresses its mtorc1 inhibitory activity.

SIGNOR-153931

Q5SQI0

P68363

1

acetylation

up-regulates quantity by stabilization

0.252

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

SIGNOR-272245

P01270

Q03431

2

binding

up-regulates

0.772

Here we show that binding of pth to its receptor pth1r induced association of lrp6, a coreceptor of wnt, with pth1r. The formation of the ternary complex containing pth, pth1r, and lrp6 promoted rapid phosphorylation of lrp6, which resulted in the recruitment of axin to lrp6, and stabilization of beta-catenin.

SIGNOR-182039

P17181

P05000

2

binding

up-regulates

0.728

Ifn-alpha, ifn-beta, and ifn-omega, induce somewhat different cellular effects but act through a common receptor complex, ifnar, composed of subunits ifnar-1 and ifnar-2.

SIGNOR-105979

Q9Y4C0

P58417

2

binding

up-regulates

0.375

We show that neurexophilins 1 and 3 but not 4 (neurexophilin 2 is not expressed in rodents) bind to a single individual lns domain, the second overall lns domain in all three alpha-neurexins.

SIGNOR-60643

P13807

Q86XI6

2

binding

up-regulates

0.714

In the liver, PTG and PPP1R3B(GL)are expressed at roughly equivalent levels [55], and they jointly promote hepatic glycogen mobilization and storage. PTG overexpression significantly increased glycogen content, mainly due to its ability to promote the redistribution of PP1 and glycogen synthase to glycogen granules, significantly increasing GS activity and glycogen synthesis (Figure 2)

SIGNOR-271734

Q14832

P63092

2

binding

up-regulates activity

0.35

MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.

SIGNOR-264083

Q92831

Q06413

2

binding

up-regulates

0.573

The cofactors grip-1, cbp/p300 and pcaf have hat activity and function as co-activators for mef-2c during myogenesis.

SIGNOR-84032

P62805

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-265376

Q9UQL6

Q9Y463

0

phosphorylation

down-regulates activity

0.372

Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent mannermirk phosphorylates hdac5 at ser-279

SIGNOR-235809

Q13202

Q16539

1

dephosphorylation

down-regulates

0.591

M3/6 (dusp8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of jnk and, to a lesser extent, p38 mapk

SIGNOR-199695

Q9UHC7

Q8N726

1

polyubiquitination

down-regulates quantity by destabilization

0.366

Biochemical analyses confirmed that MKRN1 targets p14ARF for ubiquitination and subsequent proteasome-dependent degradation.The Skp1-Cul1-F-box-protein44 (SCF(FBXO44)) complex ubiquitinates full-length BRCA1 in vitro.

SIGNOR-272036

Q14152

Q9Y6E2

2

binding

up-regulates activity

0.324

BZW2, as an evolutionary highly conserved protein, interacts with eIF2 and eIF3 and promotes ternary complex formation in vitro

SIGNOR-261221

Q13315

Q9H981

1

phosphorylation

down-regulates activity

0.2

These findings indicate that ATM dependent phosphorylation on ARP8-S412 reduces ARP8 INO80 interaction.|These findings raised the possibility that ATM negatively regulates the interaction of ARP8 with INO80 after etoposide treatment.

SIGNOR-279437

P21860

Q9H4P4

0

polyubiquitination

down-regulates quantity by destabilization

0.691

Nrdp1/FLRF is a ubiquitin ligase promoting ubiquitination and degradation of the epidermal growth factor receptor family member, ErbB3

SIGNOR-272599

P51813

P12931

0

phosphorylation

up-regulates

0.535

Coexpression of v-src and etk led to a transphosphorylation on tyrosine 566 of etk and subsequent autophosphorylation. These events correlated with a substantial increase in the kinase activity of etk.

SIGNOR-75330

Q9NRR5

Q13315

0

phosphorylation

up-regulates activity

0.2

These results suggest that UBQLN4 phosphorylation on S318 is functionally important for its role in the DSB response.>Particularly HRR is dependent on ATM activity (Dietlein et al., 2014). Here, we showed that UBQLN4 is an ATM substrate and that DSB sealing is markedly impaired in UBQLN4-depleted cells. HRR depends on a 5′-3′ DSB end resection, which is initiated by the MRE11 nuclease

SIGNOR-265076

P16104

Q14676

2

binding

up-regulates

0.2

Here, we demonstrate that mammalian mdc1/nfbd1 directly binds to phospho-h2ax (gammah2ax) by specifically interacting with the phosphoepitope at the gammah2ax carboxyl terminus.

SIGNOR-143377

Q02750

Q9UHA4

2

binding

up-regulates

0.615

We analyzed the ability of mp1 to bind to mek1, erk1, and to itself, and the regulation of these interactions. Gel filtration of cell lysates revealed two major mp1 peaks: a broad high molecular weight peak and a 28 kda complex. An mp1 mutant that lost mek1 binding no longer enhanced rasv12-stimulated erk1 activity, and functioned as a dominant negative, consistent with the concept that mp1 function depends on facilitating these oligomerizations.

SIGNOR-130924

Q9UIG0

P16104

1

phosphorylation

up-regulates

0.2

We show that wstf phosphorylates tyr 142 of h2a.x, and that wstf activity has an important role in regulating several events that are critical for the dna damage response

SIGNOR-182831

Q9HCK8

P35716

1

transcriptional regulation

down-regulates quantity

0.2

Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells

SIGNOR-268923

O14920

Q9Y6Q9

1

phosphorylation

up-regulates activity

0.378

We demonstrated the in vitro phosphorylation of SRC-3 by the two catalytic subunits of the IKK complex, IKKα and IKKβ. IKK kinase activity is required for synergistic activation with SRC-3

SIGNOR-251298

P22612

Q92934

1

phosphorylation

down-regulates

0.434

Ser-155 is the major phosphoacceptor site for pka on bad, but that pka also phosphorylates ser-112 and ser-136. Phosphorylated bad appears to be the inactive moiety. These results implicate pkac as the candidate kinase for s112 phosphorylation in vivo.

SIGNOR-81153

P51532

P37275

2

binding

up-regulates

0.404

Zeb1 represses e-cadherin transcription / we reported that brg1 binds to the ntr of zeb1 acting as its co-repressor in the regulation of the e-cadherin promoter.

SIGNOR-165017

Q04206

Q06187

0

phosphorylation

up-regulates activity

0.403

Btk induces the phosphorylation of NF-\u03baB p65 which can be induced by the expression of inflammation cytokines [ ].|Btk induces the phosphorylation of NF-\u03baB p65 which can be induced by the expression of inflammation cytokines [ xref ].

SIGNOR-280197

P16473

P63092

2

binding

up-regulates activity

0.663

The primary signal transduction pathway for TSH receptor is activation of adenylate cyclase via a Gαs G protein-coupled receptor.

SIGNOR-267136

Q8N4X5

P07949

0

phosphorylation

up-regulates activity

0.33

RET/PTC induced robust tyrosine phosphorylation of XB130, which promoted its subsequent association with the p85alpha subunit of phosphatidylinositol 3-kinase (PI 3-kinase). We identified tyrosine 54 of XB130 as the major target of RET/PTC-mediated phosphorylation and a critical binding site for the SH2 domains of p85alpha.

SIGNOR-263192

Q9NW38

Q9NVI1

1

ubiquitination

up-regulates activity

0.842

Phosphorylation of FANCD2 and Fanconi anemia core components (broken pink circles) affects the efficiency of, but is not essential for, ID ubiquitination by the FA core complex, together with E1 and UBE2T. Analogously, ubiquitination of FANCD2 (solid orange ovals) is essential for DNA repair, activating the ID complex for chromatin binding

SIGNOR-263266

O43164

P31323

1

polyubiquitination

down-regulates quantity by destabilization

0.2

Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits

SIGNOR-271858

Q9C040

P07196

1

ubiquitination

down-regulates quantity by destabilization

0.43

Here, we show that TRIM RING finger protein TRIM2, highly expressed in the nervous system, is an UbcH5a-dependent ubiquitin ligase. We further demonstrate that TRIM2 binds to neurofilament light subunit (NF-L) and regulates NF-L ubiquitination.

SIGNOR-271776

Q14289

Q02535

1

phosphorylation

up-regulates quantity

0.2

Taken together these findings demonstrated that Pyk2 mediates the expression of ID3 protein.|Together these findings from the combined MS+MS/MS data confirm that Flag tagged ID3 is phosphorylated by active recombinant Pyk2 kinase; and support the phospho-Tyr band that was detected at the corresponding MW ~ 13 kDA for Flag-ID3 by immunoblot.

SIGNOR-278496

P55347

P40424

2

binding

up-regulates activity

0.745

we show that Pbx proteins exist as stable heterodimers with a novel homeodomain protein, Prep1. Here we show that Prep1-Pbx interaction presents novel structural features: it is independent of DNA binding and of the integrity of their respective homeodomains, and requires sequences in the N-terminal portions of both proteins. The Prep1-Pbx protein-protein interaction is essential for DNA-binding activity.

SIGNOR-241212

P49715

P22415

2

binding

up-regulates activity

0.317

Our studies show that the human C/EBPa protein stimulates USF to bind to a USF consensus element within C/EBPa promoter and activates it by two- to threefold.The mechanism by which C/EBPa enhances USF binding and transactivation is currently under study.

SIGNOR-255701

Q5T9L3

P56704

1

relocalization

up-regulates activity

0.641

WNT secretion requires its binding to the carrier protein wntless (WLS);

SIGNOR-256599

Q00535

Q05682

1

phosphorylation

down-regulates quantity by destabilization

0.341

Together, these data demonstrate that phosphorylation of caldesmon on Ser527 by Cdk5 serves to down regulate its stability.

SIGNOR-280215

Q9Y271

P50148

2

binding

up-regulates activity

0.385

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

SIGNOR-257019

Q15796

P16220

2

binding

up-regulates

0.325

We demonstrate that human smad2 and smad4, two essential smad proteins involved in mediating tgf-beta transcriptional responses in endothelial and other cell types, can functionally interact with the transcriptional coactivator creb binding protein (cbp). This interaction is specific in that it requires ligand (tgf-beta) activation and is mediated by the transcriptional activation domains of the smad proteins.

SIGNOR-59462

P42574

Q9NR09

2

binding

down-regulates

0.464

Bruce binds and thereby inhibits caspases, in particular effector caspase-3.

SIGNOR-125956

Q7Z419

P06748

1

ubiquitination

down-regulates quantity by destabilization

0.2

NPMc degradation was mediated by the ubiquitin-proteasome pathway involving the IBR-type RING-finger E3 ubiquitin ligase IBRDC2, and genetic correction of FA-A or FA-C lymphoblasts prevented NPMc ubiquitination. As shown in Fig. 4C, knockdown of IBRDC2, an IBR-type RING-finger E3 ubiquitin ligase (21), significantly reduced NPMc ubiquitination and restored NPMc stability in FA-A cells

SIGNOR-271490

Q6A1A2

O00141

1

phosphorylation

up-regulates

0.2

Our results are consistent with a model in which activation of sgk by igf-1 or hydrogen peroxide is initiated by a ptdins(3,4, 5)p3-dependent activation of pdk2, which phosphorylates ser422.

SIGNOR-66234

Q9NPA2

P08253

1

cleavage

up-regulates activity

0.375

Direct activation of pro-matrix metalloproteinase-2 by leukolysin/membrane-type 6 matrix metalloproteinase/matrix metalloproteinase 25 at the asn(109)-Tyr bond. Leukolysin Cleaves ProMMP-2 at Asn66-Leu and Asn109-Tyr.

SIGNOR-256345

Q9HCE7

Q92519

1

ubiquitination

down-regulates quantity by destabilization

0.41

In this study, we found that TRIB2 was up-regulated and exhibited high stability in liver cancer cells compared with other cells. We performed a structure-function analysis of TRIB2 and identified a domain (amino acids 1-5) at the N terminus that interacted with the E3 ubiquitin ligase Smurf1 and was critical for protein stability. Deletion of this domain extended TRIB2 half-life time accompanied with a more significant malignant property compared with wild type TRIB2.

SIGNOR-275432

Q9BY11

Q9NQU5

0

phosphorylation

up-regulates activity

0.2

We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo.

SIGNOR-263021

Q96HP0

P67775

0

phosphorylation

down-regulates activity

0.2

Akt and PP2A reciprocally regulate the guanine nucleotide exchange factor Dock6 to control axon growth of sensory neurons|At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser(1194). | In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, whereas reintroduction of Dock6 with a phosphomimetic S1194E mutation resulted in premature branching

SIGNOR-275669

P36873

P42575

1

dephosphorylation

up-regulates activity

0.2

nutrient-replete oocytes inhibit C2 via S135 phosphorylation catalyzed by calcium/calmodulin-dependent protein kinase II. We now show that C2 phosphorylated at S135 binds 14-3-3zeta, thus preventing C2 dephosphorylation. Moreover, we determined that S135 dephosphorylation is catalyzed by protein phosphatase-1 (PP1), which directly binds C2.

SIGNOR-248503

P25963

P18031

0

dephosphorylation

down-regulates

0.354

Ptp1b is able to dephosphorylate phosphorylated-tyr-42 on ikappabalpha

SIGNOR-45004

P30307

P27348

0

relocalization

down-regulates

0.575

Cdc25c: nuclear exclusion/cytoplasmic sequestration via binding to 14-3-3 proteins.

SIGNOR-163237

Q12778

O15021

0

phosphorylation

down-regulates activity

0.334

MAST4 phosphorylation of FOXO1 regulates RTKN2 expression.

SIGNOR-279079

P28702

P13631

2

binding

up-regulates

0.714

Here we report that the transcriptional activity of rar and rxr can be reciprocally modulated by direct interactions between the two proteins.

SIGNOR-16683

Q92997

Q9UP38

2

binding

up-regulates activity

0.657

Upon ligand binding, DVL proteins are recruited to Frizzled receptors at the plasma membrane and co-recruit cytoplasmic transducers, such as Axin, CK1 and GSK3 binding protein (GBP), presumably along with their partners, to promote ?-catenin-dependent signalling.

SIGNOR-258953

P16220

P98177

2

binding

down-regulates activity

0.308

We provide evidence that the acetyltransferase creb-binding protein (cbp) binds foxo resulting in acetylation of foxo. This acetylation inhibits foxo transcriptional activity

SIGNOR-124711

Q13153

Q16584

0

phosphorylation

up-regulates activity

0.304

Although, MLK3 can phosphorylate PAK1 on Ser133 and Ser204 sites, PAK1S133A mutant is constitutively active, whereas, PAK1S204A is not activated by MLK3.|MLK3 was able to directly phosphorylate PAK1 on two Serine residues of which Ser204 is critical for MLK3-induced PAK1 activation and downstream functions.

SIGNOR-279418

P22681

P62993

0

relocalization

up-regulates

0.904

The underlying mechanism seems to involve recruitment of a grb2 c-cbl complex to grb2-specific docking sites of egfr, and concurrent acceleration of receptor ubiquitylation and desensitization.

SIGNOR-114704

P51955

Q9NZQ7

1

phosphorylation

up-regulates quantity by stabilization

0.2

NEK2 interacts with PD-L1, phosphorylating the T194/T210 residues and preventing ubiquitin-proteasome pathway-mediated degradation of PD-L1 in ER lumen.

SIGNOR-277314

O60346

P31751

1

dephosphorylation

down-regulates activity

0.621

The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells.

SIGNOR-248328

Q9NYA1

Q96S38

2

binding

up-regulates activity

0.384

The PSK2 domain of RPK118 is required for binding to SPHK1 as demonstrated by the results from immunoprecipitation analyses (Fig. 6) as well as yeast two-hybrid screening (Fig. 1A). The overexpression of RPK118 in COS7 cells did not cause any change in the intracellular content of SPP with repeated experiments, and RPK118 binding to SPHK1 did not alter the enzymatic activity of SPHK1 in vitro (data not shown), suggesting that RPK118 may function only as an adaptor molecule for SPHK1

SIGNOR-273744

Q96BN8

P0CG48

1

cleavage

up-regulates quantity

0.717

Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.

SIGNOR-270820

P01303

P50391

2

binding

up-regulates

0.692

Human y4 bound human pp family members in i-pyy membrane binding assays with a distinctive rank order (table 1): pp > pyy > npy > npy free acid.

SIGNOR-29633

P08238

Q9P278

2

binding

down-regulates activity

0.263

FNIP1 and FNIP2 facilitate FLCN binding to Hsp90 chaperone. Our results suggest that FNIP1 is a potent inhibitor of Hsp90 ATPase activity, as 200 nM of FNIP1 inhibits Hsp90 ATPase activity by 50-fold. FNIP2 also has shown inhibitory activity towards Hsp90; however, it required 1.6 μM of FNIP2 to inhibit the ATPase activity by eightfold. Although we use the term ‘inhibition' here, FNIPs seem only to be slowing the chaperone cycle.

SIGNOR-261416

P53350

Q8IWB6

1

phosphorylation

down-regulates quantity by destabilization

0.354

We show that phosphorylation of Tex14 by Plk1 during metaphase is required for proteosome dependent degradation of Tex14 and transition from metaphase to anaphase. Phosphorylation of Tex14 Ser431 by Plk1 promotes Tex14 depletion.

SIGNOR-273529

Q9UQM7

P48058

1

phosphorylation

up-regulates

0.592

Receptor internalization, altered;intracellular localization

SIGNOR-97546

P68400

P60484

1

phosphorylation

down-regulates activity

0.68

The C-terminal tail of PTEN is also the target of mutations in tumors. As mentioned, this region contains the main phosphorylation sites mapped to residues Ser362, Thr366, Ser370, Ser380, Thr382, Thr383, and Ser385, and the kinases involved are casein kinase 2 (CK2), GSK3_, LKB1, and MAST.84,97-101 The phosphorylation of the tail has been shown to enhance PTEN stability but at the same time decrease its phosphatase activity

SIGNOR-89830

O75925

Q99608

2

binding

down-regulates quantity by destabilization

0.297

Necdin bound to PIAS1 central domains that are highly conserved among PIAS family proteins and suppressed PIAS1-dependent sumoylation of the substrates STAT1 and PML (promyelocytic leukemia protein). Remarkably, necdin promoted degradation of PIAS1 via the ubiquitin-proteasome pathway. In transfected HEK293A cells, amino- and carboxyl-terminally truncated mutants of PIAS1 bound to necdin but failed to undergo necdin-dependent ubiquitination.

SIGNOR-253387

Q9Y5X5

P08754

2

binding

up-regulates activity

0.25

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

SIGNOR-256852

P63092

P16473

2

binding

up-regulates activity

0.663

The primary signal transduction pathway for TSH receptor is activation of adenylate cyclase via a Gαs G protein-coupled receptor.

SIGNOR-267136

Q9GZX6

Q8N6P7

2

binding

up-regulates

0.893

In addition, il-22 mediates inflammation and binds class ii cytokine receptor heterodimers il-22 ra1/crf2-4.

SIGNOR-86340

P27169

Q12772

0

transcriptional regulation

up-regulates quantity by expression

0.297

we conclude that quercetin exhibits its antiatherogenic property by eliciting the translocation of the mature SREBP2 from endoplasmic reticulum to the nucleus, where it binds to SRE-like sequence in the PON1 promoter and up-regulates PON1 gene transcription and PON1 activity.

SIGNOR-255224

Q92542

Q96BI3

2

binding

up-regulates

0.967

We show that mammalian aph-1 (maph-1), a conserved multipass membrane protein, physically associates with nicastrin and the heterodimers of the presenilin amino- and carboxyl-terminal fragments in human cell lines and in rat brain. Similar to the loss of presenilin or nicastrin, the inactivation of endogenous maph-1 using small interfering rnas results in the decrease of presenilin levels, accumulation of gamma-secretase substrates (app carboxyl-terminal fragments), and reduction of gamma-secretase products (amyloid-beta peptides and the intracellular domains of app and notch).

SIGNOR-103611

Q96JC1

Q13485

1

relocalization

down-regulates activity

0.318

The data demonstrating binding of TLP to TGF-β and activin type II receptors and selective inhibition of Smad3/Smad4 complex formation by deregulated TLP suggest that TLP is involved in localizing these receptors and Smad4 to specific intracellular compartments, where it regulates formation of Smad3/Smad4 but not Smad2/Smad4 complexes.

SIGNOR-261377

P12004

P00533

0

phosphorylation

up-regulates

0.341

Here, we show that the chromatin-bound pcna protein is phosphorylated on tyr 211, which is required for maintaining its function on chromatin and is dependent on the tyrosine kinase activity of egf receptor (egfr) in the nucleus. Phosphorylation on tyr 211 by egfr stabilizes chromatin-bound pcna protein and associated functions.

SIGNOR-150852

P42338

Q6ZUJ8

2

binding

up-regulates

0.418

This accumulation of tyrosine-phosphorylated bcap at the membrane with its associated pi3k would then allow for the catalysis of ptd ins p2 to ptd ins p3 and downstream pi3k-dependent signals. Therefore, bcap is an essential activator of the pi3k pathway downstream of tlr signaling, providing a brake to limit potentially pathogenic excessive tlr responses.

SIGNOR-191667