GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 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
O00141	P46527	1	phosphorylation	down-regulates	0.469	Activated sgk1 and p27 phosphorylation at t157, and both were inhibited by short-term rapamycin treatment and by sgk1 shrna.	SIGNOR-179117
P41240	P08575	1	phosphorylation	up-regulates	0.469	Tyrosine phosphorylation of cd45 phosphotyrosine phosphatase by p50csk kinase creates a binding site for p56lck tyrosine kinase and activates the phosphatase.	SIGNOR-26785
P00519	P01106	1	phosphorylation	up-regulates activity	0.469	Altogether, our data demonstrate that Pin1 and Abl cooperate to enhance the interaction of Myc with p300 and its resulting acetylation.\|These experiments confirmed that Myc Y74 is phosphorylated by Abl, and provided us with a reagent to detect this form of Myc in cells (see below).	SIGNOR-278196
P51955	P35222	1	phosphorylation	down-regulates quantity	0.469	NEK2 silencing reduced the phosphorylation of beta-catenin at Ser33 and Ser37, but did not decrease the level of total beta-catenin.\|NEK2 slightly decreased the level of total beta-catenin (XREF_FIG).	SIGNOR-278173
Q16665	Q15118	1	transcriptional regulation	up-regulates quantity by expression	0.469	Activation of glycolytic genes by HIF-1 is considered critical for metabolic adaptation to hypoxia through increased conversion of glucose to pyruvate and subsequently to lactate. We found that HIF-1 also actively suppresses metabolism through the tricarboxylic acid cycle (TCA) by directly trans-activating the gene encoding pyruvate dehydrogenase kinase 1 (PDK1). PDK1 inactivates the TCA cycle enzyme, pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA.	SIGNOR-267444
P32121	P08588	1	binding	down-regulates activity	0.469	The protein, termed beta-arrestin, was expressed and partially purified. It inhibited the signaling function of beta ARK-phosphorylated beta-adrenergic receptors by more than 75 percent, but not that of rhodopsin. It is proposed that beta-arrestin in concert with beta ARK effects homologous desensitization of beta-adrenergic receptors	SIGNOR-256502
Q13315	Q9H7Z6	1	phosphorylation	up-regulates activity	0.469	In this study we present evidence that MOF is phosphorylated at the threonine 392 residue (pT392-MOF) by ATM subsequent to IR induced DNA damage.\|Interestingly, ATM dependent-MOF phosphorylation increases MOF retention on DNA post-irradiation in S/G2-phase cells.	SIGNOR-278350
O95198	Q9H4A3	1	binding	down-regulates quantity by destabilization	0.469	We found that KLHL2, as well as KLHL3, was co-immunoprecipitated with all four WNK isoforms. The direct interaction of KLHL2 with WNKs was confirmed on fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3 and WNK4 within HEK293T cells, and a significant increase of WNK4 ubiquitination by KLHL2 and Cullin3 was observed both in HEK293T cells and in an in vitro ubiquitination assay. These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body.	SIGNOR-272119
P62714	P05771	1	dephosphorylation	down-regulates activity	0.469	Specifically, the threonine at position 500 (T500) on the activation loop, and T641 and S660 on the carboxyl terminus of protein kinase C beta II are phosphorylated in vivo. T500 and S660 are selectively dephosphorylated in vitro by protein phosphatase 2A to yield an enzyme that is still capable of lipid-dependent activation, whereas all three residues are dephosphorylated by protein phosphatase 1 to yield an inactive enzyme.	SIGNOR-248585
P36873	P36897	1	dephosphorylation	down-regulates	0.469	We found smad7 interacts with growth arrest and dna damage protein, gadd34, a regulatory subunit of the protein phosphatase 1 (pp1) holoenzyme, which subsequently recruits catalytic subunit of pp1 (pp1c) to dephosphorylate t?RI.	SIGNOR-121277
P17612	P10071	1	phosphorylation	down-regulates quantity	0.468	Ci/gli zinc finger proteins mediate the transcriptional effects of hedgehog protein signals. In drosophila, ci action as transcriptional repressor or activator is contingent upon hedgehog-regulated, pka-dependent proteolytic processingall six pka phosphorylation sites are required for processing of gli3.	SIGNOR-75359
O95837	Q9NQ66	1	binding	up-regulates activity	0.468	This suggests that both Gal4 and Gal6 can activate PLC b1.	SIGNOR-278119
P50461	P15172	1	binding	up-regulates activity	0.468	we found that nuclear MLP functions through a physical interaction with the muscle basic helix-loop-helix (bHLH) transcription factors MyoD, MRF4, and myogenin. we propose that it serves as a cofactor for the myogenic bHLH proteins by increasing their interaction with specific DNA regulatory elements.	SIGNOR-241116
P17612	P10070	1	phosphorylation	down-regulates	0.468	In the absence of hh ligands, cubitus interruptus (in drosophila) and gli2 and gli3 (in vertebrates) are phosphorylated by protein kinase a and glycogen synthase kinase-3beta and are proteolytically processed in vertebrates, pka-mediated phosphorylation of gli2 and gli3 initiates a phosphorylation cascade that leads to processing into repressors of transcription or frank degradation	SIGNOR-154273
Q9P0U3	Q9NP62	1	desumoylation	up-regulates activity	0.468	We show that Epac1 and Rap1, in response to cAMP, activate CaMKI to phosphorylate Ser47 in GCM1. This phosphorylation facilitates the interaction between GCM1 and the desumoylating enzyme SENP1 and thereby leads to GCM1 desumoylation and activation.	SIGNOR-262681
Q96EP1	P53350	1	polyubiquitination	down-regulates quantity by destabilization	0.468	Chfr, a mitotic stress checkpoint, plays an important role in cell cycle progression, tumor suppression and the processes that require the E3 ubiquitin ligase activity mediated by the RING finger domain. Chfr stimulates the formation of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins including Plk1 and Aurora A.	SIGNOR-271464
Q8WZ73	Q13546	1	ubiquitination	down-regulates quantity by destabilization	0.468	We report that CARP-2, a RING domain-containing ubiquitin protein ligase (E3), is a negative regulator of TNF-induced NF-kappaB activation. By virtue of its phospholipid-binding FYVE domain, CARP-2 localized to endocytic vesicles, where it interacted with internalized TNF-receptor complex, resulting in RIP ubiquitination and degradation.	SIGNOR-271482
P12931	O95297	1	phosphorylation	up-regulates	0.468	Indeed, our studies indicated that cross-linking of pzr by cona lead to activation of c-src, which may be responsible for phosphorylation of pzr and possibly other proteins. Phosphorylation of pzr in turn recruits shp-2, which by itself is an essential signal transducertyrosine residues 241 and 263 embedded in the itims are responsible for the tyrosine phosphorylation of pzr	SIGNOR-113410
O14730	Q9BYX4	1	phosphorylation	down-regulates activity	0.468	RIOK3 mediates phosphorylation of MDA5 Ser-828\|RIOK3-mediated phosphorylation of MDA5 interferes with its assembly and attenuates the innate immune response	SIGNOR-264576
Q00987	Q13547	1	ubiquitination	down-regulates quantity by destabilization	0.468	MDM2 induces ubiquitination of HDAC1 in VSMCs.\|Under calcification inducing conditions, proteasomal degradation of HDAC1 precedes VC and it is mediated by MDM2 E3 ubiquitin ligase that initiates HDAC1 K74 ubiquitination.	SIGNOR-278761
Q13490	Q14249	1	ubiquitination	up-regulates activity	0.468	Alternatively, cIAP1 may mediate a vital function of EndoG other than cell death.\|Cellular inhibitor of apoptosis protein 1 ubiquitinates endonuclease G but does not affect endonuclease G-mediated cell death.	SIGNOR-278605
Q99986	P48431	1	phosphorylation	up-regulates activity	0.468	VRK1, but not kinase-dead VRK1 (K179E), phosphorylated Sox2 (XREF_FIG).	SIGNOR-279578
P34972	P63096	1	binding	up-regulates activity	0.468	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-256700
Q14994	P19793	1	binding	up-regulates	0.468	Therefore, both car-rxr heterodimers and car monomers can contribute to the gene activating function of pbrems in car target genes.	SIGNOR-104441
Q13315	O95999	1	phosphorylation	up-regulates activity	0.468	Upon DNA damage, ATM phosphorylates the residue T91 of BCL10, promoting binding of BCL10 to RNF8 and simultaneously presenting UBC13 to RNF8.\|When cells were pre-treated with different PIKK inhibitors, the ATM specific inhibitor KU55933 efficiently reduced etoposide induced focus formation of BCL10, whereas pretreatment of cells with NU6027, an ATR specific inhibitor, or NU7026, a DNA-PKcs-specific inhibitor, did not compromise etoposide induced focus formation of BCL10 (XREF_FIG).	SIGNOR-278392
Q9BZS1	Q9NZQ7	1	transcriptional regulation	up-regulates quantity by expression	0.468	FOXP3 expression additionally increased programmed death ligand 1 (PD-L1) expression, which, when inhibited with CCL5, decreased the tumor burden and Treg infiltration in orthotopic murine, Pan-02 PDAC tumors	SIGNOR-277728
Q06187	P42229	1	phosphorylation	up-regulates activity	0.467	Ectopically expressed BTK kinase domain was capable of tyrosine-phosphorylating STAT5A both in vitro and in vivo. BTK-mediated tyrosine phosphorylation of ectopically expressed wild type (but not Tyr(694) mutant) STAT5A enhanced its DNA binding activity.	SIGNOR-250603
P28222	P63096	1	binding	up-regulates activity	0.467	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-256720
Q5S007	Q99961	1	phosphorylation	down-regulates	0.467	We show that lrrk2 affects synaptic endocytosis by phosphorylating endoa at s75, a residue in the bar domain / our work uncovers a regulatory mechanism that indicates that reduced lrrk2 kinase activity facilitates endoa membrane association, while increased kinase activity inhibits membrane association.	SIGNOR-192068
P45983	Q14934	1	phosphorylation	up-regulates activity	0.467	Here, we showed that the nuclear factor of activated T3 (NFAT3) is phosphorylated by JNK1 or JNK2 at Ser(213) and Ser(217), which are located in the conserved SP motif.\|Moreover, a 3xNFAT-luc reporter gene assay indicated that NFAT3 transcriptional activity was increased in a dose dependent manner by JNK1 or JNK2.	SIGNOR-280033
P61244	Q9BW11	1	binding	up-regulates activity	0.467	the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences.	SIGNOR-240393
P17612	Q9UMX1	1	phosphorylation	up-regulates quantity by stabilization	0.467	We report that Sufu is phosphorylated at Ser-342 and Ser-346 by GSK3? and cAMP-dependent protein kinase A (PKA), respectively, and phosphorylation at this dual site stabilizes Sufu against Shh signaling-induced degradation	SIGNOR-172003
Q14995	O00327	1	transcriptional regulation	down-regulates quantity by repression	0.467	A retinoic acid receptor-related orphan receptor (ROR) response element within the BMAL1 promoter is responsive to both ROR and REV-ERB (encoded by the genes NR1D1 and NR1D2); ROR activates the transcription of BMAL1, whereas REV-ERB suppresses its transcription.	SIGNOR-268006
P53350	Q92574	1	phosphorylation	down-regulates quantity by destabilization	0.467	The Hsp90 client Plk1 phosphorylates Sgt1, which had a positive impact on Sgt1 function, whereas phosphorylation of Tsc1 by Plk1 led to its ubiquitination and degradation.	SIGNOR-280072
Q9Y618	Q96T58	1	binding	up-regulates	0.467	Sharp is a potent transcriptional repressor whose repression domain (rd) interacts directly with smrt	SIGNOR-107260
P06241	Q99490	1	phosphorylation	up-regulates	0.467	We demonstrate that fyn is essential for phosphorylating pike-a and protects it from apoptotic cleavage. Active but not kinase-dead fyn interacts with pike-a and phosphorylates it on both y682 and y774 residues. Tyrosine phosphorylation in pike-a is required for its association with active fyn but not for akt. Mutation of d into a in pike-a protects it from caspase cleavage and promotes cell survival.	SIGNOR-147936
Q92843	Q16611	1	binding	down-regulates	0.467	Bax is held in check by mcl1, bcl-2, and either bcl2l1 or bcl2l2, or by all four. They bind a primed conformer of bak or bax.	SIGNOR-152989
O14965	O15360	1	phosphorylation	up-regulates activity	0.467	E detected interactions between Aurora A kinase and FANCA protein, one of the components of the FA nuclear core complex. These results suggest that S165 phosphorylation by Aurora A kinase is required for proper activation of the FA/BRCA pathway in response to DNA damage.	SIGNOR-277263
P53350	O95239	1	phosphorylation	down-regulates activity	0.467	Moreover, phosphorylation of KIF4 and condensin I by Aurora B and polo like kinase 1 (Plk1) is important for KIF4 and condensin I localization to the chromosome.\|These results suggest that Plk1 negatively regulates the loading of both KIF4 and condensin to the chromosome.	SIGNOR-280069
Q9UBY5	Q03113	1	binding	up-regulates	0.467	Serum-borne lysophosphatidic acid (lpa) and sphingosine 1-phosphophate (s1p) act through g12/13-coupled receptors to inhibit the hippo pathway kinases lats1/2 thereby activating yap and taz transcription co-activators, which are oncoproteins repressed by lats1/2.	SIGNOR-198544
P19086	Q08828	1	binding	down-regulates activity	0.467	Activated a z inhibits the activity of type I and type V adenylyl cyclases.	SIGNOR-278044
P31749	P13631	1	phosphorylation	up-regulates activity	0.467	S379 of RARγ is indispensable for the CLDN6-triggered cellular events. The most important finding of the present study is that the CLDN6/SFK/PI3K/AKT signaling controls the RARγ and ERα activities (Fig. 6).	SIGNOR-277492
P28482	Q14247	1	phosphorylation	up-regulates	0.467	Cortactin is regulated by multiple phosphorylation events, including phosphorylation of s405 and s418 by extracellular regulated kinases (erk)1/2. Erk1/2 phosphorylation of cortactin has emerged as an important positive regulatory modification, enabling cortactin to bind and activate the arp2/3 regulator neuronal wiskott-aldrich syndrome protein (n-wasp), promoting actin polymerization and enhancing tumor cell movement.	SIGNOR-165200
P31314	P14921	1	binding	down-regulates activity	0.467	We show that the cortical thymic maturation arrest in T-lineage ALLs that overexpress TLX1 or TLX3 is due to binding of TLX1/TLX3 to ETS1, leading to repression of T cell receptor (TCR) α enhanceosome activity and blocked TCR-Jα rearrangement.	SIGNOR-259097
O15550	P09017	1	transcriptional regulation	up-regulates quantity by expression	0.467	Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.	SIGNOR-260030
Q92997	P63000	1	binding	up-regulates	0.467	Wnt/fz activation of rac and rho is inhibited by rac-n17 and rho-n19, respectively (figs. _(figs.1d,1d, _d,5c,d;5c,d;habas et al. 2001), and requires different dvl domains wnt signaling induces complex formation between dvl and rac.	SIGNOR-97409
Q9UK97	O43156	1	binding	down-regulates quantity by destabilization	0.467	Here we report that Tel2 and Tti1 are targeted for degradation within mTORC1 by the SCFFbxo9 ubiquitin ligase to adjust mTOR signalling to growth factor availability. The interaction between Tel2/Tti1 and Fbxo9 identified by mass spectrometry suggests that SCFFbxo9 is probably the ubiquitin ligase that mediates degradation of both proteins.	SIGNOR-271997
P78527	Q9UGP5	1	phosphorylation	up-regulates activity	0.467	We show that Polλ is efficiently phosphorylated by DNA-PKcs in vitro and predominantly by ATM after DSB induction with ionizing radiation (IR) in vivo. We identify threonine 204 (T204) as a main target for ATM/DNA-PKcs phosphorylation on human Polλ, and establish that its phosphorylation may facilitate the repair of a subset of IR-induced DSBs and the efficient Polλ-mediated gap-filling during NHEJ.	SIGNOR-273835
O43765	P46379	1	binding	up-regulates activity	0.467	USP13 and gp78 control ubiquitination of Ubl4A.These data suggest that USP13 and gp78 play antagonizing roles in regulation of Ubl4A ubiquitination: While gp78 assembles ubiquitin chains on Ubl4A, USP13 antagonizes this activity to limit Ubl4A ubiquitination.Ubiquitination of Ubl4A preferentially occurs on Lys48. We identify the Bag6 cofactor Ubl4A as a shared substrate of gp78 and USP13. USP13 depletion is associated with hyper-ubiquitination of Ubl4A and altered interaction between the Bag6 complex and its co-chaperone SGTA. Because the interaction of Ubl4A with SGTA is mediated by positively-charged residues in Ubl4A including Lys48 (Chartron et al., 2012; Xu et al., 2012), which happens to be the major ubiquitination site, the simplest model to explain reduced Bag6-SGTA interaction in USP13 knockdown cells is that ubiquitin conjugates on Ubl4A sterically hinder SGTA binding.	SIGNOR-272859
P37173	Q9NPB6	1	phosphorylation	up-regulates	0.466	We demonstrate that Par6, a regulator of epithelial cell polarity and tight-junction assembly, interacts with TGFbeta receptors and is a substrate of the type II receptor, TbetaRII. [...] These data suggest that T_RII phosphorylates Par6 at its penultimate residue, Ser345.	SIGNOR-227484
P46934	Q00987	1	ubiquitination	up-regulates quantity by stabilization	0.466	NEDD4 promotes MDM2 ubiquitination in a dose- and time-dependent manner, whereas depletion of NEDD4 reduced the half-life of endogenous MDM2 [ xref ].	SIGNOR-278769
Q9UNE7	Q9Y4K3	1	ubiquitination	down-regulates quantity by destabilization	0.466	CHIP promotes TRAF6 ubiquitination and degradation.\|These results suggest that CHIP negatively regulates the stability of TRAF6.	SIGNOR-278670
Q9H093	O14974	1	phosphorylation	down-regulates activity	0.466	NUAK2 phosphorylates and inhibits MYPT1, the regulatory subunit of MLC phosphatase, stabilizing actin filaments and mediating contraction of smooth muscle cells ( xref ).	SIGNOR-279081
P06493	O00429	1	phosphorylation	up-regulates activity	0.466	Drp1 is phosphorylated at the Ser616 position and activated predominantly by CDK1.	SIGNOR-279394
P43405	P10636	1	phosphorylation	down-regulates	0.466	We established that tyrosine 18 was the primary residue in tau phosphorylated by sykphosphorylation of tau by syk could be involved in neurite outgrowth.	SIGNOR-159648
O95835	Q8NHZ8	1	phosphorylation	up-regulates activity	0.466	LATS1 and LATS2 phosphorylate CDC26 to modulate assembly of the tetratricopeptide repeat subcomplex of APC/C\|Overall, these results suggest that LATS1/2 are novel kinases involved in APC/C phosphorylation and indicate a direct regulatory link between LATS1/2 and APC/C\|Here, we demonstrate that LATS1 phosphorylates the Thr7 (T7) residue of the APC/C component CDC26 directly	SIGNOR-275472
P28482	Q09472	1	phosphorylation	up-regulates	0.466	Erk2-mediated c-terminal serine phosphorylation of p300 (ser-2279, ser-2315, and ser-2366) is vital to the regulation of epidermal growth factor-induced keratin 16 gene expression.	SIGNOR-156891
P12931	P49789	1	phosphorylation	up-regulates activity	0.466	The human tumor suppressor Fhit is a homodimeric histidine triad (HIT) protein of 147 amino acids which has Ap3A hydrolase activity. We have recently discovered that Fhit is phosphorylated in vivo and is phosphorylated in vitro by Src kinaseMALDI-TOF and HPLC-ESI tandem mass spectrometry of intact Fhit and proteolytic peptides of Fhit demonstrated that Fhit is phosphorylated on Y114 on either one or both subunitsThe decreases in the values of Km and kcat for the phosphorylated forms in comparison to those of unphosphorylated Fhit favor the formation and lifetime of the Fhit_Ap3A complex, which may enhance the tumor suppressor activity of Fhit.	SIGNOR-247134
P09919	P15509	1	binding	up-regulates	0.466	Granulocyte-macrophage colony-stimulating factor (gm-csf) is an important hematopoietic cytokine that exerts its effects by interaction with the gm-csf receptor (gmr) on the surface of responsive cells. The gm-csf receptor consists of two subunits: gmralpha, which binds gm-csf with low affinity, and gmrbeta, which lacks intrinsic ligand-binding capability but complexes with gmralpha to form a high-affinity receptor (gmralpha/beta).	SIGNOR-72511
Q9Y478	Q8N122	1	phosphorylation	down-regulates	0.466	Ampk in turn inactivates mtorc1 directly by phosphorylating raptor and indirectly by phosphorylating tsc2.	SIGNOR-173041
Q15139	O95863	1	phosphorylation	down-regulates activity	0.466	Pkd1 phosphorylates ser(11) (s11) on transcription factor snail, a master emt regulator and repressor of e-cadherin expression, triggering nuclear export of snail via 14-3-3_ binding. Pkd1 regulates the expression of e-cadherin at the promoter level through direct phosphorylation of the transcriptional repressor snai1. Pkd1-mediated phosphorylation of snai1 occurs in the nucleus and generates a nuclear, inactive dna/snai1 complex that shows decreased interaction with its co-repressor ajuba.	SIGNOR-168537
O43613	P50148	1	binding	up-regulates activity	0.466	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-257220
Q8N6D2	P27449	1	polyubiquitination	down-regulates quantity by destabilization	0.466	The data indicated that RNF182 targeted ATP6V0C for degradation by the ubiquitin-proteosome pathway.	SIGNOR-271771
O43184	P31431	1	binding	up-regulates	0.466	The adam12 cysteine-rich domain (radam12-cys) supports cell attachment using syndecan-4 as a primary cell surface receptor that subsequently triggers beta(1) integrin-dependent cell spreading, stress fiber assembly, and focal adhesion formation.	SIGNOR-96931
Q92993	Q01130	1	acetylation	down-regulates	0.466	In this study, we provide the first evidence that the acetyltransferase tip60 acetylates srsf2 on its lysine 52 residue inside the rna recognition motif, and promotes its proteasomal degradation.	SIGNOR-170594
Q86VP1	Q13114	1	binding	down-regulates activity	0.466	ABIN1 interacted with the A20 regulatory molecule TAX1BP1 and was essential for the recruitment of TAX1BP1 and A20 to the noncanonical IkappaB kinases TBK1 and IKKi in response to poly(I:C) transfection. ABIN1 and TAX1BP1 together disrupted the interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKKi to attenuate lysine 63-linked polyubiquitination of TBK1/IKKi.	SIGNOR-275737
Q96GF1	O14641	1	polyubiquitination	down-regulates quantity by destabilization	0.466	The E3 ligase RNF185 negatively regulates osteogenic differentiation by targeting Dvl2 for degradation. Overexpression of RNF185 decreases the exogenous and endogenous level of Dvl2, promotes the ubiquitination and degradation of Dvl2	SIGNOR-272173
Q02535	Q99081	1	binding	down-regulates activity	0.466	All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo.	SIGNOR-241152
P07948	P78527	1	phosphorylation	down-regulates activity	0.466	The interaction between Lyn and DNA-PKcs inhibits DNA-PKcs activity and the ability of DNA-PKcs to form a complex with Ku/DNA.\|We also show that Lyn phosphorylates DNA-PKcs but not Ku in vitro.	SIGNOR-279061
P51608	P06850	1	transcriptional regulation	down-regulates quantity by repression	0.466	Collectively, these results point to a specific association between WT MeCP2 and the methylated promoter region of Crh in vivo. In contrast, the MeCP2308 protein was not detected at the Crh promoter. \| Thus, the results of seqChIP indicate that MeCP2 preferentially associates with a transcriptionally inactive, dimethyl-histone H3 Lys-9-rich form of the Crh promoter in mice.	SIGNOR-264548
P31749	O15519	1	phosphorylation	down-regulates quantity	0.466	TNFalpha enhanced FLIP(L) serine phosphorylation, which was increased by activated Akt-1. Serine 273, a putative Akt-1 phosphorylation site in FLIP(L), was critical for the activation-induced reduction of FLIP(L). Thus, these observations document a novel mechanism where by TNFalpha facilitates the reduction of FLIP(L) protein, which is dependent on the phosphatidylinositol 3-kinase/Akt signaling.	SIGNOR-252548
P42574	Q06609	1	cleavage	down-regulates quantity by destabilization	0.466	The RAD51 protein has been shown to be a substrate for caspase-3\|he activated caspase-3 fragments (19 kDa and 17 kDa) and caspase-3 cleaved RAD51 fragment (∼23 kDa) was detected by Western analysis (Figure 3E). Activation of caspase-3 and the signature proteolytic degradation product of RAD51 only occurred in parental 32Dcl3 cells after treatment with cisplatin	SIGNOR-271709
Q9UQC2	P42336	1	binding	up-regulates	0.466	The signaling mechanism utilizes an adaptor protein, shc, which binds to a phosphotyrosine residue on the il-2/15r?, Resulting in activation of grb2 and onto akt via the shc-grb2-gab2-pi3k-akt signaling pathway to increase cell proliferation and/or survival	SIGNOR-204966
Q12923	P35568	1	dephosphorylation	down-regulates activity	0.466	Finally, we report that PTPL1 expression is sufficient to block the IRS-1/phosphatidylinositol 3-kinase/Akt signaling pathway, to inhibit the insulin-like growth factor-I effect on cell survival, and to induce apoptosis.\|We first show by complementary approaches that PTPL1 specifically dephosphorylates insulin receptor substrate-1 (IRS-1) in vitro and in cellulo.	SIGNOR-277053
O00192	P19022	1	binding	up-regulates quantity by stabilization	0.466	To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member.	SIGNOR-252128
P32238	P50148	1	binding	up-regulates activity	0.465	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-257303
Q12772	Q8NBP7	1	transcriptional regulation	up-regulates quantity by expression	0.465	Recent studies have demonstrated that PCSK9 mRNA expression was upregulated to a greater extent than that of the LDL receptor in human hepatocytes in primary culture. Our findings also support the role of SREBP-2 as a transcriptional regulator of both the LDL receptor and PCSK9 in human enterocytes.	SIGNOR-254459
P16519	P10997	1	cleavage	up-regulates activity	0.465	The processing of proinsulin to insulin occurs in the secretory granules at the C-terminal end of pairs of basic amino acids, Arg31-Arg32 and Lys64-Arg65 [9,10]. Following cleavage, by the prohormone convertases, PC3 (also known as PC1) and PC2, the pair of basic amino acids are removed rapidly by carboxypeptidase E (CPE) to produce the mature insulin molecule	SIGNOR-261791
P17612	P48436	1	phosphorylation	up-regulates	0.465	We find that activation of camp-dependent protein kinase a (pka) induces phosphorylation of sox9 on its two s64 and s181 pka sites, and its nuclear localization by enhancing sox9 binding to the nucleocytoplasmic transport protein importin beta.	SIGNOR-137085
P49841	P54252	1	phosphorylation	up-regulates quantity by stabilization	0.465	Phosphorylation of ataxin-3 by glycogen synthase kinase 3beta at serine 256 regulates the aggregation of ataxin-3\|	SIGNOR-264821
P31749	Q13107	1	phosphorylation	up-regulates quantity by stabilization	0.465	AKT-mediated phosphorylation relocates nuclear USP4 to the cytoplasm and membrane and is required for maintaining its protein stability.	SIGNOR-273482
P06493	O00562	1	phosphorylation	up-regulates	0.465	T287 is phosphorylated by cdk1 during mitosis. Phosphorylation of nir2 by cdk1 facilitates its dissociation from the golgi apparatus, and phospho-nir2(ps382) is localized in the cleavage furrow and midbody during cytokinesis.	SIGNOR-124642
Q96R06	Q96SN8	1	relocalization	up-regulates activity	0.465	By bringing CDK5RAP2 to the centrosome, the centriolar satellite proteins CEP72 and SPAG5 are required for the centrosomal localization of the other three MCPH proteins despite not interacting with them biochemically.	SIGNOR-271719
P31749	P78362	1	phosphorylation	up-regulates	0.465	Here we show that srpk2, a protein kinase specific for the serine/arginine (sr) family of splicing factors, triggers cell cycle progression in neurons and induces apoptosis through regulation of nuclear cyclin d1. Akt phosphorylates srpk2 on thr-492 and promotes its nuclear translocation leading to cyclin d1 up-regulation, cell cycle reentry, and neuronal apoptosis.	SIGNOR-186760
P0DP23	O00418	1	binding	up-regulates	0.465	The calmodulin-binding region is located between amino acids 51 and 96	SIGNOR-82505
P12931	Q12774	1	phosphorylation	up-regulates activity	0.465	Arhgef5 was tyrosine-phosphorylated by Src and bound to Src to positively regulate its activity.\|Using an inducible system for Src activation, we found that Src induced podosome formation depends upon the Src SH3 domain, and identified Arhgef5 as a Src SH3 binding protein.	SIGNOR-279571
Q4KMG0	Q16539	1	binding	up-regulates activity	0.465	During myoblast differentiation, the promyogenic cell surface receptor cdo binds to the p38alpha/beta pathway scaffold protein jlp and, via jlp, p38alpha/beta itself	SIGNOR-179867
P53350	Q00987	1	phosphorylation	up-regulates	0.465	Here we show that the oncogenic and cell cycle-regulatory protein kinase, polo-like kinase-1 (plk1), phosphorylates mdm2 at one of these residues, ser260, and stimulates mdm2-mediated turnover of p53. These data are consistent with the idea that deregulation of plk1 during tumourigenesis may help suppress p53 function.	SIGNOR-94272
P53350	O14641	1	phosphorylation	up-regulates	0.465	Dvl2 bound to and was phosphorylated at thr206 by a mitotic kinase, polo-like kinase 1 (plk1), and this phosphorylation was required for spindle orientation and stable microtubule (mt)-kt attachment	SIGNOR-167858
P24941	Q96EB6	1	phosphorylation	up-regulates activity	0.465	Sirt1 is in turn phosphorylated by Cdk2, which may further regulate its activity.\|Taken together, these data demonstrate that Cdk2 deletion does not decrease Hif1\u03b1 expression induced by HX, and strongly suggests that the phosphorylation of Sirt1 at Ser47 by Cdk2 requires Sirt1 deacetylase activity.	SIGNOR-279513
O15297	O60341	1	dephosphorylation	down-regulates activity	0.465	We demonstrated here that phosphorylation and dephosphorylation of LSD1 at S131 and S137 was mediated by casein kinase 2 (CK2) and wild-type p53-induced phosphatase 1 (WIP1), respectively. LSD1, RNF168 and 53BP1 interacted with each other directly. CK2-mediated phosphorylation of LSD1 exhibited no impact on its interaction with 53BP1, but promoted its interaction with RNF168 and RNF168-dependent 53BP1 ubiquitination and subsequent recruitment to the DNA damage sites.	SIGNOR-276905
Q00987	O94992	1	ubiquitination	up-regulates activity	0.465	Here we report that human double minute-2 protein (HDM2), a p53-specific E3 ubiquitin ligase, specifically ubiquitinates HEXIM1 through the lysine residues located within the basic region of HEXIM1.\|However, the HDM2-induced HEXIM1 ubiquitination does not lead to proteasome-mediated protein degradation.	SIGNOR-278701
Q14669	Q8IYW5	1	ubiquitination	down-regulates activity	0.465	Here, we show that TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage. We find that RNF168 can be saturated by increasing amounts of DSBs. Depletion of TRIP12 and UBR5 allows accumulation of RNF168 to supraphysiological levels, followed by massive spreading of ubiquitin conjugates and hyperaccumulation of ubiquitin-regulated genome caretakers such as 53BP1 and BRCA1.	SIGNOR-266783
Q92794	Q01196	1	binding	up-regulates	0.465	The activation domain of aml1 is required for its interaction with moz / moz activates aml1_mediated transcription	SIGNOR-113056
P35462	P09471	1	binding	up-regulates activity	0.465	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-256981
P31749	Q99497	1	phosphorylation	up-regulates activity	0.465	Using a proteomic approach, we identified on DJ-1 a novel threonine phosphorylation (T125) that was found, by the in-silico tool scansite 4, as part of a putative Akt consensus. \|Deglycase activity of DJ-1 on histones proteins, investigated by coupling 2D tau gel with LC-MS/MS and 2D-TAU (Triton-Acid-Urea)-Western blot, was found correlated with its phosphorylation status that, in turn, depends from Akt activation.	SIGNOR-275582
P22415	P15407	1	binding	down-regulates activity	0.465	USF specifically interacts with Fra1. USF was repressing this modest Fra1 transactivation	SIGNOR-240975
P31749	P99999	1	phosphorylation	down-regulates activity	0.465	Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain.	SIGNOR-277237
P68400	P18146	1	phosphorylation	down-regulates activity	0.464	Casein kinase II associates with Egr-1 and acts as a negative modulator of its DNA binding and transcription activities in NIH 3T3 cells. \| There are three CKII recognition sites (S376XXD, T389XE, and T516XXXD) in fragment 10.	SIGNOR-250858
Q9BVJ7	Q9NP62	1	dephosphorylation	up-regulates quantity by stabilization	0.464	DUSP23 prevents GCM1 from ubiquitination and prolongs the half-life of GCM1.\|Second, DUSP23 is able to dephosphorylate Ser322 in GCM1 in vitro and in a stable cell line expressing HA-GCM1.	SIGNOR-276982

O00141

P46527

1

phosphorylation

down-regulates

0.469

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

SIGNOR-179117

P41240

P08575

1

phosphorylation

up-regulates

0.469

Tyrosine phosphorylation of cd45 phosphotyrosine phosphatase by p50csk kinase creates a binding site for p56lck tyrosine kinase and activates the phosphatase.

SIGNOR-26785

P00519

P01106

1

phosphorylation

up-regulates activity

0.469

Altogether, our data demonstrate that Pin1 and Abl cooperate to enhance the interaction of Myc with p300 and its resulting acetylation.|These experiments confirmed that Myc Y74 is phosphorylated by Abl, and provided us with a reagent to detect this form of Myc in cells (see below).

SIGNOR-278196

P51955

P35222

1

phosphorylation

down-regulates quantity

0.469

NEK2 silencing reduced the phosphorylation of beta-catenin at Ser33 and Ser37, but did not decrease the level of total beta-catenin.|NEK2 slightly decreased the level of total beta-catenin (XREF_FIG).

SIGNOR-278173

Q16665

Q15118

1

transcriptional regulation

up-regulates quantity by expression

0.469

Activation of glycolytic genes by HIF-1 is considered critical for metabolic adaptation to hypoxia through increased conversion of glucose to pyruvate and subsequently to lactate. We found that HIF-1 also actively suppresses metabolism through the tricarboxylic acid cycle (TCA) by directly trans-activating the gene encoding pyruvate dehydrogenase kinase 1 (PDK1). PDK1 inactivates the TCA cycle enzyme, pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA.

SIGNOR-267444

P32121

P08588

1

binding

down-regulates activity

0.469

The protein, termed beta-arrestin, was expressed and partially purified. It inhibited the signaling function of beta ARK-phosphorylated beta-adrenergic receptors by more than 75 percent, but not that of rhodopsin. It is proposed that beta-arrestin in concert with beta ARK effects homologous desensitization of beta-adrenergic receptors

SIGNOR-256502

Q13315

Q9H7Z6

1

phosphorylation

up-regulates activity

0.469

In this study we present evidence that MOF is phosphorylated at the threonine 392 residue (pT392-MOF) by ATM subsequent to IR induced DNA damage.|Interestingly, ATM dependent-MOF phosphorylation increases MOF retention on DNA post-irradiation in S/G2-phase cells.

SIGNOR-278350

O95198

Q9H4A3

1

binding

down-regulates quantity by destabilization

0.469

We found that KLHL2, as well as KLHL3, was co-immunoprecipitated with all four WNK isoforms. The direct interaction of KLHL2 with WNKs was confirmed on fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3 and WNK4 within HEK293T cells, and a significant increase of WNK4 ubiquitination by KLHL2 and Cullin3 was observed both in HEK293T cells and in an in vitro ubiquitination assay. These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body.

SIGNOR-272119

P62714

P05771

1

dephosphorylation

down-regulates activity

0.469

Specifically, the threonine at position 500 (T500) on the activation loop, and T641 and S660 on the carboxyl terminus of protein kinase C beta II are phosphorylated in vivo. T500 and S660 are selectively dephosphorylated in vitro by protein phosphatase 2A to yield an enzyme that is still capable of lipid-dependent activation, whereas all three residues are dephosphorylated by protein phosphatase 1 to yield an inactive enzyme.

SIGNOR-248585

P36873

P36897

1

dephosphorylation

down-regulates

0.469

We found smad7 interacts with growth arrest and dna damage protein, gadd34, a regulatory subunit of the protein phosphatase 1 (pp1) holoenzyme, which subsequently recruits catalytic subunit of pp1 (pp1c) to dephosphorylate t?RI.

SIGNOR-121277

P17612

P10071

1

phosphorylation

down-regulates quantity

0.468

Ci/gli zinc finger proteins mediate the transcriptional effects of hedgehog protein signals. In drosophila, ci action as transcriptional repressor or activator is contingent upon hedgehog-regulated, pka-dependent proteolytic processingall six pka phosphorylation sites are required for processing of gli3.

SIGNOR-75359

O95837

Q9NQ66

1

binding

up-regulates activity

0.468

This suggests that both Gal4 and Gal6 can activate PLC b1.

SIGNOR-278119

P50461

P15172

1

binding

up-regulates activity

0.468

we found that nuclear MLP functions through a physical interaction with the muscle basic helix-loop-helix (bHLH) transcription factors MyoD, MRF4, and myogenin. we propose that it serves as a cofactor for the myogenic bHLH proteins by increasing their interaction with specific DNA regulatory elements.

SIGNOR-241116

P17612

P10070

1

phosphorylation

down-regulates

0.468

In the absence of hh ligands, cubitus interruptus (in drosophila) and gli2 and gli3 (in vertebrates) are phosphorylated by protein kinase a and glycogen synthase kinase-3beta and are proteolytically processed in vertebrates, pka-mediated phosphorylation of gli2 and gli3 initiates a phosphorylation cascade that leads to processing into repressors of transcription or frank degradation

SIGNOR-154273

Q9P0U3

Q9NP62

1

desumoylation

up-regulates activity

0.468

We show that Epac1 and Rap1, in response to cAMP, activate CaMKI to phosphorylate Ser47 in GCM1. This phosphorylation facilitates the interaction between GCM1 and the desumoylating enzyme SENP1 and thereby leads to GCM1 desumoylation and activation.

SIGNOR-262681

Q96EP1

P53350

1

polyubiquitination

down-regulates quantity by destabilization

0.468

Chfr, a mitotic stress checkpoint, plays an important role in cell cycle progression, tumor suppression and the processes that require the E3 ubiquitin ligase activity mediated by the RING finger domain. Chfr stimulates the formation of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins including Plk1 and Aurora A.

SIGNOR-271464

Q8WZ73

Q13546

1

ubiquitination

down-regulates quantity by destabilization

0.468

We report that CARP-2, a RING domain-containing ubiquitin protein ligase (E3), is a negative regulator of TNF-induced NF-kappaB activation. By virtue of its phospholipid-binding FYVE domain, CARP-2 localized to endocytic vesicles, where it interacted with internalized TNF-receptor complex, resulting in RIP ubiquitination and degradation.

SIGNOR-271482

P12931

O95297

1

phosphorylation

up-regulates

0.468

Indeed, our studies indicated that cross-linking of pzr by cona lead to activation of c-src, which may be responsible for phosphorylation of pzr and possibly other proteins. Phosphorylation of pzr in turn recruits shp-2, which by itself is an essential signal transducertyrosine residues 241 and 263 embedded in the itims are responsible for the tyrosine phosphorylation of pzr

SIGNOR-113410

O14730

Q9BYX4

1

phosphorylation

down-regulates activity

0.468

RIOK3 mediates phosphorylation of MDA5 Ser-828|RIOK3-mediated phosphorylation of MDA5 interferes with its assembly and attenuates the innate immune response

SIGNOR-264576

Q00987

Q13547

1

ubiquitination

down-regulates quantity by destabilization

0.468

MDM2 induces ubiquitination of HDAC1 in VSMCs.|Under calcification inducing conditions, proteasomal degradation of HDAC1 precedes VC and it is mediated by MDM2 E3 ubiquitin ligase that initiates HDAC1 K74 ubiquitination.

SIGNOR-278761

Q13490

Q14249

1

ubiquitination

up-regulates activity

0.468

Alternatively, cIAP1 may mediate a vital function of EndoG other than cell death.|Cellular inhibitor of apoptosis protein 1 ubiquitinates endonuclease G but does not affect endonuclease G-mediated cell death.

SIGNOR-278605

Q99986

P48431

1

phosphorylation

up-regulates activity

0.468

VRK1, but not kinase-dead VRK1 (K179E), phosphorylated Sox2 (XREF_FIG).

SIGNOR-279578

P34972

P63096

1

binding

up-regulates activity

0.468

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-256700

Q14994

P19793

1

binding

up-regulates

0.468

Therefore, both car-rxr heterodimers and car monomers can contribute to the gene activating function of pbrems in car target genes.

SIGNOR-104441

Q13315

O95999

1

phosphorylation

up-regulates activity

0.468

Upon DNA damage, ATM phosphorylates the residue T91 of BCL10, promoting binding of BCL10 to RNF8 and simultaneously presenting UBC13 to RNF8.|When cells were pre-treated with different PIKK inhibitors, the ATM specific inhibitor KU55933 efficiently reduced etoposide induced focus formation of BCL10, whereas pretreatment of cells with NU6027, an ATR specific inhibitor, or NU7026, a DNA-PKcs-specific inhibitor, did not compromise etoposide induced focus formation of BCL10 (XREF_FIG).

SIGNOR-278392

Q9BZS1

Q9NZQ7

1

transcriptional regulation

up-regulates quantity by expression

0.468

FOXP3 expression additionally increased programmed death ligand 1 (PD-L1) expression, which, when inhibited with CCL5, decreased the tumor burden and Treg infiltration in orthotopic murine, Pan-02 PDAC tumors

SIGNOR-277728

Q06187

P42229

1

phosphorylation

up-regulates activity

0.467

Ectopically expressed BTK kinase domain was capable of tyrosine-phosphorylating STAT5A both in vitro and in vivo. BTK-mediated tyrosine phosphorylation of ectopically expressed wild type (but not Tyr(694) mutant) STAT5A enhanced its DNA binding activity.

SIGNOR-250603

P28222

P63096

1

binding

up-regulates activity

0.467

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-256720

Q5S007

Q99961

1

phosphorylation

down-regulates

0.467

We show that lrrk2 affects synaptic endocytosis by phosphorylating endoa at s75, a residue in the bar domain / our work uncovers a regulatory mechanism that indicates that reduced lrrk2 kinase activity facilitates endoa membrane association, while increased kinase activity inhibits membrane association.

SIGNOR-192068

P45983

Q14934

1

phosphorylation

up-regulates activity

0.467

Here, we showed that the nuclear factor of activated T3 (NFAT3) is phosphorylated by JNK1 or JNK2 at Ser(213) and Ser(217), which are located in the conserved SP motif.|Moreover, a 3xNFAT-luc reporter gene assay indicated that NFAT3 transcriptional activity was increased in a dose dependent manner by JNK1 or JNK2.

SIGNOR-280033

P61244

Q9BW11

1

binding

up-regulates activity

0.467

the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences.

SIGNOR-240393

P17612

Q9UMX1

1

phosphorylation

up-regulates quantity by stabilization

0.467

We report that Sufu is phosphorylated at Ser-342 and Ser-346 by GSK3? and cAMP-dependent protein kinase A (PKA), respectively, and phosphorylation at this dual site stabilizes Sufu against Shh signaling-induced degradation

SIGNOR-172003

Q14995

O00327

1

transcriptional regulation

down-regulates quantity by repression

0.467

A retinoic acid receptor-related orphan receptor (ROR) response element within the BMAL1 promoter is responsive to both ROR and REV-ERB (encoded by the genes NR1D1 and NR1D2); ROR activates the transcription of BMAL1, whereas REV-ERB suppresses its transcription.

SIGNOR-268006

P53350

Q92574

1

phosphorylation

down-regulates quantity by destabilization

0.467

The Hsp90 client Plk1 phosphorylates Sgt1, which had a positive impact on Sgt1 function, whereas phosphorylation of Tsc1 by Plk1 led to its ubiquitination and degradation.

SIGNOR-280072

Q9Y618

Q96T58

1

binding

up-regulates

0.467

Sharp is a potent transcriptional repressor whose repression domain (rd) interacts directly with smrt

SIGNOR-107260

P06241

Q99490

1

phosphorylation

up-regulates

0.467

We demonstrate that fyn is essential for phosphorylating pike-a and protects it from apoptotic cleavage. Active but not kinase-dead fyn interacts with pike-a and phosphorylates it on both y682 and y774 residues. Tyrosine phosphorylation in pike-a is required for its association with active fyn but not for akt. Mutation of d into a in pike-a protects it from caspase cleavage and promotes cell survival.

SIGNOR-147936

Q92843

Q16611

1

binding

down-regulates

0.467

Bax is held in check by mcl1, bcl-2, and either bcl2l1 or bcl2l2, or by all four. They bind a primed conformer of bak or bax.

SIGNOR-152989

O14965

O15360

1

phosphorylation

up-regulates activity

0.467

E detected interactions between Aurora A kinase and FANCA protein, one of the components of the FA nuclear core complex. These results suggest that S165 phosphorylation by Aurora A kinase is required for proper activation of the FA/BRCA pathway in response to DNA damage.

SIGNOR-277263

P53350

O95239

1

phosphorylation

down-regulates activity

0.467

Moreover, phosphorylation of KIF4 and condensin I by Aurora B and polo like kinase 1 (Plk1) is important for KIF4 and condensin I localization to the chromosome.|These results suggest that Plk1 negatively regulates the loading of both KIF4 and condensin to the chromosome.

SIGNOR-280069

Q9UBY5

Q03113

1

binding

up-regulates

0.467

Serum-borne lysophosphatidic acid (lpa) and sphingosine 1-phosphophate (s1p) act through g12/13-coupled receptors to inhibit the hippo pathway kinases lats1/2 thereby activating yap and taz transcription co-activators, which are oncoproteins repressed by lats1/2.

SIGNOR-198544

P19086

Q08828

1

binding

down-regulates activity

0.467

Activated a z inhibits the activity of type I and type V adenylyl cyclases.

SIGNOR-278044

P31749

P13631

1

phosphorylation

up-regulates activity

0.467

S379 of RARγ is indispensable for the CLDN6-triggered cellular events. The most important finding of the present study is that the CLDN6/SFK/PI3K/AKT signaling controls the RARγ and ERα activities (Fig. 6).

SIGNOR-277492

P28482

Q14247

1

phosphorylation

up-regulates

0.467

Cortactin is regulated by multiple phosphorylation events, including phosphorylation of s405 and s418 by extracellular regulated kinases (erk)1/2. Erk1/2 phosphorylation of cortactin has emerged as an important positive regulatory modification, enabling cortactin to bind and activate the arp2/3 regulator neuronal wiskott-aldrich syndrome protein (n-wasp), promoting actin polymerization and enhancing tumor cell movement.

SIGNOR-165200

P31314

P14921

1

binding

down-regulates activity

0.467

We show that the cortical thymic maturation arrest in T-lineage ALLs that overexpress TLX1 or TLX3 is due to binding of TLX1/TLX3 to ETS1, leading to repression of T cell receptor (TCR) α enhanceosome activity and blocked TCR-Jα rearrangement.

SIGNOR-259097

O15550

P09017

1

transcriptional regulation

up-regulates quantity by expression

0.467

Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.

SIGNOR-260030

Q92997

P63000

1

binding

up-regulates

0.467

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

SIGNOR-97409

Q9UK97

O43156

1

binding

down-regulates quantity by destabilization

0.467

Here we report that Tel2 and Tti1 are targeted for degradation within mTORC1 by the SCFFbxo9 ubiquitin ligase to adjust mTOR signalling to growth factor availability. The interaction between Tel2/Tti1 and Fbxo9 identified by mass spectrometry suggests that SCFFbxo9 is probably the ubiquitin ligase that mediates degradation of both proteins.

SIGNOR-271997

P78527

Q9UGP5

1

phosphorylation

up-regulates activity

0.467

We show that Polλ is efficiently phosphorylated by DNA-PKcs in vitro and predominantly by ATM after DSB induction with ionizing radiation (IR) in vivo. We identify threonine 204 (T204) as a main target for ATM/DNA-PKcs phosphorylation on human Polλ, and establish that its phosphorylation may facilitate the repair of a subset of IR-induced DSBs and the efficient Polλ-mediated gap-filling during NHEJ.

SIGNOR-273835

O43765

P46379

1

binding

up-regulates activity

0.467

USP13 and gp78 control ubiquitination of Ubl4A.These data suggest that USP13 and gp78 play antagonizing roles in regulation of Ubl4A ubiquitination: While gp78 assembles ubiquitin chains on Ubl4A, USP13 antagonizes this activity to limit Ubl4A ubiquitination.Ubiquitination of Ubl4A preferentially occurs on Lys48. We identify the Bag6 cofactor Ubl4A as a shared substrate of gp78 and USP13. USP13 depletion is associated with hyper-ubiquitination of Ubl4A and altered interaction between the Bag6 complex and its co-chaperone SGTA. Because the interaction of Ubl4A with SGTA is mediated by positively-charged residues in Ubl4A including Lys48 (Chartron et al., 2012; Xu et al., 2012), which happens to be the major ubiquitination site, the simplest model to explain reduced Bag6-SGTA interaction in USP13 knockdown cells is that ubiquitin conjugates on Ubl4A sterically hinder SGTA binding.

SIGNOR-272859

P37173

Q9NPB6

1

phosphorylation

up-regulates

0.466

We demonstrate that Par6, a regulator of epithelial cell polarity and tight-junction assembly, interacts with TGFbeta receptors and is a substrate of the type II receptor, TbetaRII. [...] These data suggest that T_RII phosphorylates Par6 at its penultimate residue, Ser345.

SIGNOR-227484

P46934

Q00987

1

ubiquitination

up-regulates quantity by stabilization

0.466

NEDD4 promotes MDM2 ubiquitination in a dose- and time-dependent manner, whereas depletion of NEDD4 reduced the half-life of endogenous MDM2 [ xref ].

SIGNOR-278769

Q9UNE7

Q9Y4K3

1

ubiquitination

down-regulates quantity by destabilization

0.466

CHIP promotes TRAF6 ubiquitination and degradation.|These results suggest that CHIP negatively regulates the stability of TRAF6.

SIGNOR-278670

Q9H093

O14974

1

phosphorylation

down-regulates activity

0.466

NUAK2 phosphorylates and inhibits MYPT1, the regulatory subunit of MLC phosphatase, stabilizing actin filaments and mediating contraction of smooth muscle cells ( xref ).

SIGNOR-279081

P06493

O00429

1

phosphorylation

up-regulates activity

0.466

Drp1 is phosphorylated at the Ser616 position and activated predominantly by CDK1.

SIGNOR-279394

P43405

P10636

1

phosphorylation

down-regulates

0.466

We established that tyrosine 18 was the primary residue in tau phosphorylated by sykphosphorylation of tau by syk could be involved in neurite outgrowth.

SIGNOR-159648

O95835

Q8NHZ8

1

phosphorylation

up-regulates activity

0.466

LATS1 and LATS2 phosphorylate CDC26 to modulate assembly of the tetratricopeptide repeat subcomplex of APC/C|Overall, these results suggest that LATS1/2 are novel kinases involved in APC/C phosphorylation and indicate a direct regulatory link between LATS1/2 and APC/C|Here, we demonstrate that LATS1 phosphorylates the Thr7 (T7) residue of the APC/C component CDC26 directly

SIGNOR-275472

P28482

Q09472

1

phosphorylation

up-regulates

0.466

Erk2-mediated c-terminal serine phosphorylation of p300 (ser-2279, ser-2315, and ser-2366) is vital to the regulation of epidermal growth factor-induced keratin 16 gene expression.

SIGNOR-156891

P12931

P49789

1

phosphorylation

up-regulates activity

0.466

The human tumor suppressor Fhit is a homodimeric histidine triad (HIT) protein of 147 amino acids which has Ap3A hydrolase activity. We have recently discovered that Fhit is phosphorylated in vivo and is phosphorylated in vitro by Src kinaseMALDI-TOF and HPLC-ESI tandem mass spectrometry of intact Fhit and proteolytic peptides of Fhit demonstrated that Fhit is phosphorylated on Y114 on either one or both subunitsThe decreases in the values of Km and kcat for the phosphorylated forms in comparison to those of unphosphorylated Fhit favor the formation and lifetime of the Fhit_Ap3A complex, which may enhance the tumor suppressor activity of Fhit.

SIGNOR-247134

P09919

P15509

1

binding

up-regulates

0.466

Granulocyte-macrophage colony-stimulating factor (gm-csf) is an important hematopoietic cytokine that exerts its effects by interaction with the gm-csf receptor (gmr) on the surface of responsive cells. The gm-csf receptor consists of two subunits: gmralpha, which binds gm-csf with low affinity, and gmrbeta, which lacks intrinsic ligand-binding capability but complexes with gmralpha to form a high-affinity receptor (gmralpha/beta).

SIGNOR-72511

Q9Y478

Q8N122

1

phosphorylation

down-regulates

0.466

Ampk in turn inactivates mtorc1 directly by phosphorylating raptor and indirectly by phosphorylating tsc2.

SIGNOR-173041

Q15139

O95863

1

phosphorylation

down-regulates activity

0.466

Pkd1 phosphorylates ser(11) (s11) on transcription factor snail, a master emt regulator and repressor of e-cadherin expression, triggering nuclear export of snail via 14-3-3_ binding. Pkd1 regulates the expression of e-cadherin at the promoter level through direct phosphorylation of the transcriptional repressor snai1. Pkd1-mediated phosphorylation of snai1 occurs in the nucleus and generates a nuclear, inactive dna/snai1 complex that shows decreased interaction with its co-repressor ajuba.

SIGNOR-168537

O43613

P50148

1

binding

up-regulates activity

0.466

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-257220

Q8N6D2

P27449

1

polyubiquitination

down-regulates quantity by destabilization

0.466

The data indicated that RNF182 targeted ATP6V0C for degradation by the ubiquitin-proteosome pathway.

SIGNOR-271771

O43184

P31431

1

binding

up-regulates

0.466

The adam12 cysteine-rich domain (radam12-cys) supports cell attachment using syndecan-4 as a primary cell surface receptor that subsequently triggers beta(1) integrin-dependent cell spreading, stress fiber assembly, and focal adhesion formation.

SIGNOR-96931

Q92993

Q01130

1

acetylation

down-regulates

0.466

In this study, we provide the first evidence that the acetyltransferase tip60 acetylates srsf2 on its lysine 52 residue inside the rna recognition motif, and promotes its proteasomal degradation.

SIGNOR-170594

Q86VP1

Q13114

1

binding

down-regulates activity

0.466

ABIN1 interacted with the A20 regulatory molecule TAX1BP1 and was essential for the recruitment of TAX1BP1 and A20 to the noncanonical IkappaB kinases TBK1 and IKKi in response to poly(I:C) transfection. ABIN1 and TAX1BP1 together disrupted the interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKKi to attenuate lysine 63-linked polyubiquitination of TBK1/IKKi.

SIGNOR-275737

Q96GF1

O14641

1

polyubiquitination

down-regulates quantity by destabilization

0.466

The E3 ligase RNF185 negatively regulates osteogenic differentiation by targeting Dvl2 for degradation. Overexpression of RNF185 decreases the exogenous and endogenous level of Dvl2, promotes the ubiquitination and degradation of Dvl2

SIGNOR-272173

Q02535

Q99081

1

binding

down-regulates activity

0.466

All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo.

SIGNOR-241152

P07948

P78527

1

phosphorylation

down-regulates activity

0.466

The interaction between Lyn and DNA-PKcs inhibits DNA-PKcs activity and the ability of DNA-PKcs to form a complex with Ku/DNA.|We also show that Lyn phosphorylates DNA-PKcs but not Ku in vitro.

SIGNOR-279061

P51608

P06850

1

transcriptional regulation

down-regulates quantity by repression

0.466

Collectively, these results point to a specific association between WT MeCP2 and the methylated promoter region of Crh in vivo. In contrast, the MeCP2308 protein was not detected at the Crh promoter. | Thus, the results of seqChIP indicate that MeCP2 preferentially associates with a transcriptionally inactive, dimethyl-histone H3 Lys-9-rich form of the Crh promoter in mice.

SIGNOR-264548

P31749

O15519

1

phosphorylation

down-regulates quantity

0.466

TNFalpha enhanced FLIP(L) serine phosphorylation, which was increased by activated Akt-1. Serine 273, a putative Akt-1 phosphorylation site in FLIP(L), was critical for the activation-induced reduction of FLIP(L). Thus, these observations document a novel mechanism where by TNFalpha facilitates the reduction of FLIP(L) protein, which is dependent on the phosphatidylinositol 3-kinase/Akt signaling.

SIGNOR-252548

P42574

Q06609

1

cleavage

down-regulates quantity by destabilization

0.466

The RAD51 protein has been shown to be a substrate for caspase-3|he activated caspase-3 fragments (19 kDa and 17 kDa) and caspase-3 cleaved RAD51 fragment (∼23 kDa) was detected by Western analysis (Figure 3E). Activation of caspase-3 and the signature proteolytic degradation product of RAD51 only occurred in parental 32Dcl3 cells after treatment with cisplatin

SIGNOR-271709

Q9UQC2

P42336

1

binding

up-regulates

0.466

The signaling mechanism utilizes an adaptor protein, shc, which binds to a phosphotyrosine residue on the il-2/15r?, Resulting in activation of grb2 and onto akt via the shc-grb2-gab2-pi3k-akt signaling pathway to increase cell proliferation and/or survival

SIGNOR-204966

Q12923

P35568

1

dephosphorylation

down-regulates activity

0.466

Finally, we report that PTPL1 expression is sufficient to block the IRS-1/phosphatidylinositol 3-kinase/Akt signaling pathway, to inhibit the insulin-like growth factor-I effect on cell survival, and to induce apoptosis.|We first show by complementary approaches that PTPL1 specifically dephosphorylates insulin receptor substrate-1 (IRS-1) in vitro and in cellulo.

SIGNOR-277053

O00192

P19022

1

binding

up-regulates quantity by stabilization

0.466

To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member.

SIGNOR-252128

P32238

P50148

1

binding

up-regulates activity

0.465

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-257303

Q12772

Q8NBP7

1

transcriptional regulation

up-regulates quantity by expression

0.465

Recent studies have demonstrated that PCSK9 mRNA expression was upregulated to a greater extent than that of the LDL receptor in human hepatocytes in primary culture. Our findings also support the role of SREBP-2 as a transcriptional regulator of both the LDL receptor and PCSK9 in human enterocytes.

SIGNOR-254459

P16519

P10997

1

cleavage

up-regulates activity

0.465

The processing of proinsulin to insulin occurs in the secretory granules at the C-terminal end of pairs of basic amino acids, Arg31-Arg32 and Lys64-Arg65 [9,10]. Following cleavage, by the prohormone convertases, PC3 (also known as PC1) and PC2, the pair of basic amino acids are removed rapidly by carboxypeptidase E (CPE) to produce the mature insulin molecule

SIGNOR-261791

P17612

P48436

1

phosphorylation

up-regulates

0.465

We find that activation of camp-dependent protein kinase a (pka) induces phosphorylation of sox9 on its two s64 and s181 pka sites, and its nuclear localization by enhancing sox9 binding to the nucleocytoplasmic transport protein importin beta.

SIGNOR-137085

P49841

P54252

1

phosphorylation

up-regulates quantity by stabilization

0.465

Phosphorylation of ataxin-3 by glycogen synthase kinase 3beta at serine 256 regulates the aggregation of ataxin-3|

SIGNOR-264821

P31749

Q13107

1

phosphorylation

up-regulates quantity by stabilization

0.465

AKT-mediated phosphorylation relocates nuclear USP4 to the cytoplasm and membrane and is required for maintaining its protein stability.

SIGNOR-273482

P06493

O00562

1

phosphorylation

up-regulates

0.465

T287 is phosphorylated by cdk1 during mitosis. Phosphorylation of nir2 by cdk1 facilitates its dissociation from the golgi apparatus, and phospho-nir2(ps382) is localized in the cleavage furrow and midbody during cytokinesis.

SIGNOR-124642

Q96R06

Q96SN8

1

relocalization

up-regulates activity

0.465

By bringing CDK5RAP2 to the centrosome, the centriolar satellite proteins CEP72 and SPAG5 are required for the centrosomal localization of the other three MCPH proteins despite not interacting with them biochemically.

SIGNOR-271719

P31749

P78362

1

phosphorylation

up-regulates

0.465

Here we show that srpk2, a protein kinase specific for the serine/arginine (sr) family of splicing factors, triggers cell cycle progression in neurons and induces apoptosis through regulation of nuclear cyclin d1. Akt phosphorylates srpk2 on thr-492 and promotes its nuclear translocation leading to cyclin d1 up-regulation, cell cycle reentry, and neuronal apoptosis.

SIGNOR-186760

P0DP23

O00418

1

binding

up-regulates

0.465

The calmodulin-binding region is located between amino acids 51 and 96

SIGNOR-82505

P12931

Q12774

1

phosphorylation

up-regulates activity

0.465

Arhgef5 was tyrosine-phosphorylated by Src and bound to Src to positively regulate its activity.|Using an inducible system for Src activation, we found that Src induced podosome formation depends upon the Src SH3 domain, and identified Arhgef5 as a Src SH3 binding protein.

SIGNOR-279571

Q4KMG0

Q16539

1

binding

up-regulates activity

0.465

During myoblast differentiation, the promyogenic cell surface receptor cdo binds to the p38alpha/beta pathway scaffold protein jlp and, via jlp, p38alpha/beta itself

SIGNOR-179867

P53350

Q00987

1

phosphorylation

up-regulates

0.465

Here we show that the oncogenic and cell cycle-regulatory protein kinase, polo-like kinase-1 (plk1), phosphorylates mdm2 at one of these residues, ser260, and stimulates mdm2-mediated turnover of p53. These data are consistent with the idea that deregulation of plk1 during tumourigenesis may help suppress p53 function.

SIGNOR-94272

P53350

O14641

1

phosphorylation

up-regulates

0.465

Dvl2 bound to and was phosphorylated at thr206 by a mitotic kinase, polo-like kinase 1 (plk1), and this phosphorylation was required for spindle orientation and stable microtubule (mt)-kt attachment

SIGNOR-167858

P24941

Q96EB6

1

phosphorylation

up-regulates activity

0.465

Sirt1 is in turn phosphorylated by Cdk2, which may further regulate its activity.|Taken together, these data demonstrate that Cdk2 deletion does not decrease Hif1\u03b1 expression induced by HX, and strongly suggests that the phosphorylation of Sirt1 at Ser47 by Cdk2 requires Sirt1 deacetylase activity.

SIGNOR-279513

O15297

O60341

1

dephosphorylation

down-regulates activity

0.465

We demonstrated here that phosphorylation and dephosphorylation of LSD1 at S131 and S137 was mediated by casein kinase 2 (CK2) and wild-type p53-induced phosphatase 1 (WIP1), respectively. LSD1, RNF168 and 53BP1 interacted with each other directly. CK2-mediated phosphorylation of LSD1 exhibited no impact on its interaction with 53BP1, but promoted its interaction with RNF168 and RNF168-dependent 53BP1 ubiquitination and subsequent recruitment to the DNA damage sites.

SIGNOR-276905

Q00987

O94992

1

ubiquitination

up-regulates activity

0.465

Here we report that human double minute-2 protein (HDM2), a p53-specific E3 ubiquitin ligase, specifically ubiquitinates HEXIM1 through the lysine residues located within the basic region of HEXIM1.|However, the HDM2-induced HEXIM1 ubiquitination does not lead to proteasome-mediated protein degradation.

SIGNOR-278701

Q14669

Q8IYW5

1

ubiquitination

down-regulates activity

0.465

Here, we show that TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage. We find that RNF168 can be saturated by increasing amounts of DSBs. Depletion of TRIP12 and UBR5 allows accumulation of RNF168 to supraphysiological levels, followed by massive spreading of ubiquitin conjugates and hyperaccumulation of ubiquitin-regulated genome caretakers such as 53BP1 and BRCA1.

SIGNOR-266783

Q92794

Q01196

1

binding

up-regulates

0.465

The activation domain of aml1 is required for its interaction with moz / moz activates aml1_mediated transcription

SIGNOR-113056

P35462

P09471

1

binding

up-regulates activity

0.465

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-256981

P31749

Q99497

1

phosphorylation

up-regulates activity

0.465

Using a proteomic approach, we identified on DJ-1 a novel threonine phosphorylation (T125) that was found, by the in-silico tool scansite 4, as part of a putative Akt consensus. |Deglycase activity of DJ-1 on histones proteins, investigated by coupling 2D tau gel with LC-MS/MS and 2D-TAU (Triton-Acid-Urea)-Western blot, was found correlated with its phosphorylation status that, in turn, depends from Akt activation.

SIGNOR-275582

P22415

P15407

1

binding

down-regulates activity

0.465

USF specifically interacts with Fra1. USF was repressing this modest Fra1 transactivation

SIGNOR-240975

P31749

P99999

1

phosphorylation

down-regulates activity

0.465

Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain.

SIGNOR-277237

P68400

P18146

1

phosphorylation

down-regulates activity

0.464

Casein kinase II associates with Egr-1 and acts as a negative modulator of its DNA binding and transcription activities in NIH 3T3 cells. | There are three CKII recognition sites (S376XXD, T389XE, and T516XXXD) in fragment 10.

SIGNOR-250858

Q9BVJ7

Q9NP62

1

dephosphorylation

up-regulates quantity by stabilization

0.464

DUSP23 prevents GCM1 from ubiquitination and prolongs the half-life of GCM1.|Second, DUSP23 is able to dephosphorylate Ser322 in GCM1 in vitro and in a stable cell line expressing HA-GCM1.

SIGNOR-276982