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
P27361	Q9NQ66	1	phosphorylation	up-regulates activity	0.412	Plc beta1 could be efficiently phosphorylated by activated mitogen-activated protein kinase but not by pka. The erk phosphorylation site was mapped to serine 982	SIGNOR-106565
P06493	Q8IXJ6	1	phosphorylation	down-regulates	0.412	Here, we demonstrate that sirt2 is phosphorylated both in vitro and in vivo on serine 368 by the cell-cycle regulator, cyclin-dependent kinase 1. Overexpression of sirt2 mediates a delay in cellular proliferation that is dependent on serine 368 phosphorylation.	SIGNOR-154681
P58294	Q8TCW9	1	binding	up-regulates	0.412	The present study demonstrates that eg-vegf/prokineticin 1 and a peptide closely related to eg-vegf, prokineticin 2, are cognate ligands of two orphan g-protein-coupled receptors designated zaq (=eg-vegf/pk-r1) and i5e (=eg-vegf/pk-r2)	SIGNOR-89084
Q9UBI6	P31751	1	binding	up-regulates	0.412	We show that pge2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (g protein) coupled receptor, ep2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase akt by free g protein bg subunits and the direct association of the g protein as subunit with the regulator of g protein signaling (rgs) domain of axin. This leads to the inactivation and release of glycogen synthase kinase 3b from its complex with axin, thereby relieving the inhibitory phosphorylation of b-catenin and activating its signaling pathway.	SIGNOR-141792
P04637	P52789	1	transcriptional regulation	down-regulates quantity by repression	0.412	P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway.	SIGNOR-267466
P52292	O43148	1	binding	down-regulates activity	0.412	KPNA2 Inhibits RNMT Activity\|We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor.	SIGNOR-265502
P12931	Q01196	1	phosphorylation	up-regulates activity	0.412	Src phosphorylates Runx1 on one central and four C-terminal tyrosines.\|We find that activated Src synergizes with Runx1 to activate a Runx1 luciferase reporter.	SIGNOR-279656
P10523	Q93034	1	binding	up-regulates quantity by stabilization	0.412	Here we report that NEDD4-1, a HECT domain-containing E3 ubiquitin ligase, binds via its HECT domain directly with SAG's C-terminal RING domain and ubiquitylates SAG for proteasome-mediated. We also found that SAG bridges NEDD4-1 via its C-terminus and CUL-5 via its N-terminus to form a NEDD4-1/SAG/CUL-5 tri-complex. Biologically, NEDD4-1 overexpression sensitizes cancer cells to etoposide-induced apoptosis by reducing SAG levels through targeted degradation. Thus, SAG is added to a growing list of NEDD4-1 substrates and mediates its biological function. degradation.	SIGNOR-272844
P00519	O60504	1	phosphorylation	up-regulates activity	0.412	Abl kinase interacts with and phosphorylates vinexin.	SIGNOR-280172
Q13557	Q08289	1	phosphorylation	up-regulates	0.412	We recently identified ca(v)1.2 beta(2a) residues critical for camkii phosphorylation (thr 498) beta(2a) thr 498 and leu 493 are required for ca(v)1.2 activation by camkii in native cells.	SIGNOR-164067
O00533	Q12955	1	relocalization	up-regulates quantity	0.412	Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.	SIGNOR-266723
P42345	Q13322	1	phosphorylation	up-regulates	0.412	The adaptor protein grb10 was identified as an mtorc1 substrate that mediates the phosphoinositide 3-kinase.	SIGNOR-174071
P31749	P09651	1	phosphorylation	down-regulates	0.412	Our data also suggest that akt negatively regulates hnrnp a1-mediated ires activity via phosphorylation at ser199.	SIGNOR-252519
P49841	P41236	1	phosphorylation	up-regulates activity	0.412	Protein phosphatase 1 (PP1) is complexed with inhibitor 2 (I-2) in the cytosol. In rabbit muscle extract PP1.I-2 is activated upon preincubation with ATP/Mg. This activation is caused by phosphorylation of I-2 on Thr(72) by glycogen synthase kinase 3 (GSK3).	SIGNOR-251257
P01106	P06733	2	transcriptional regulation	up-regulates quantity	0.411	C-Myc directly transactivates genes encoding GLUT1, phosphofructokinase, and enolase and increases glucose uptake in Rat1 fibroblasts. Nuclear run-on studies confirmed that the GLUT1 transcriptional rate is elevated by c-Myc. Our findings suggest that overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway.	SIGNOR-259989
P12931	Q15139	1	phosphorylation	up-regulates	0.411	Critical for the regulation of pkd1 activity in response to oxidative stress are src- and abl-mediated tyrosine phosphorylations that eventually lead to protein kinase cdelta (pkcdelta)-mediated activation of pkd1. our data suggest that pkd1 phosphorylation at tyr95 generates a binding motif for pkcdelta, and that oxidative stress-mediated pkcdelta/pkd interaction results in pkd1 activation loop phosphorylation and activation.	SIGNOR-157716
P20309	O95837	1	binding	up-regulates activity	0.411	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257134
Q13627	Q14814	1	phosphorylation	down-regulates activity	0.411	DYRK1A phosphorylates MEF2D and decreases its transcriptional activity	SIGNOR-277901
Q9Y2K2	P56524	1	phosphorylation	down-regulates activity	0.411	They find that SIK3 phosphorylates and inhibits HDAC4 during feeding states.\|They find that SIK3 phosphorylates and inhibits HDAC4 during feeding\nstates.	SIGNOR-279430
P43657	P50148	1	binding	up-regulates	0.411	Lysophosphatidic acid (lpa), a major g protein coupled receptor (gpcr)-activating ligand present in serum, elicits growth factor like responses by stimulating specific gpcrs coupled to heterotrimeric g proteins such as g(i), g(q), and g12/13.	SIGNOR-135822
P31629	P30874	1	transcriptional regulation	up-regulates quantity by expression	0.411	Activation of somatostatin receptor II expression by transcription factors MIBP1 and SEF-2 in the murine brain.	SIGNOR-261617
O96017	Q13263	1	phosphorylation	down-regulates activity	0.411	In particular, Chk2 phosphorylates KAP1 on Ser473 decreasing the interaction between KAP1 and HP1 proteins: this post translational modification promotes HP1\u03b2 mobilization and the reorganization of chromatin structure favoring the repair of DNA breaks inside heterochromatin [ , ].\|Of note, phosphorylation of S473 by Chk2 decreases the interaction between KAP1 and HP1 proteins and is necessary for HP1\u03b2 mobilization, a key event for DNA repair in the heterochromatin [ - ].	SIGNOR-279730
P06733	P01106	2	transcriptional regulation	down-regulates quantity by repression	0.411	This result suggests that MBP-1 in vivo acts as a sequence-specific repressor.	SIGNOR-261594
P35240	Q13043	1	binding	up-regulates activity	0.411	NF2 is activated by oxidative stress in cardiomyocytes and mouse myocardium and facilitates apoptosis. NF2 promotes I/R injury through activation of Mst1 and inhibition of Yap, thereby regulating Hippo signaling in the adult heart.	SIGNOR-261956
Q96Q15	P04637	1	phosphorylation	up-regulates	0.411	Hsmg-1 is a stress-activated kinase that phosphorylates p53 and hupf1 in vitrothe observation that hsmg-1 exhibits p53 (ser-15) kinase activity in vitro suggested that this pikk might be involved in genotoxic stress-induced p53 phosphorylation and stabilization in intact cells.	SIGNOR-125135
P49840	P13807	1	phosphorylation	down-regulates	0.411	Glycogen synthase kinase-3 (gsk-3) phosphorylates four serine residues in the cooh terminus of glycogen synthase. Phosphorylation of one of these residues, ser640 (site 3a), causes strong inactivation of glycogen synthase	SIGNOR-118927
Q5S007	P15311	1	phosphorylation	up-regulates activity	0.411	LRRK2 also phosphorylated ezrin and radixin, which are related to moesin, at the residue equivalent to Thr558, as well as a peptide (LRRKtide: RLGRDKYKTLRQIRQ) encompassing Thr558.	SIGNOR-279202
P24941	P33981	1	phosphorylation	up-regulates quantity by stabilization	0.411	Cdk2 phosphorylates Mps1 at T468, attenuating the function of a degradation signal found in amino acids 420\u2013507 (encoded by exons 12 and 13) and allowing the accumulation of a centrosomal pool of Mps1 that represents no more than 10% of total cellular Mps1 ( xref ).	SIGNOR-279398
Q15011	P11021	1	relocalization	up-regulates quantity by stabilization	0.411	A key inhibitor of the turnover and Nt-arginylation of BiP was HERP (homocysteine-responsive ER protein), a 43-kDa ER membrane-integrated protein that is an essential component of ER-associated protein degradation.	SIGNOR-261346
Q9P278	P07900	1	binding	down-regulates activity	0.411	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-261414
P54762	Q92823	1	phosphorylation	up-regulates activity	0.411	EphB receptors were found to induce phosphorylation of NrCAM on the tyrosine residue within the FIGQY ankyrin binding motif, inhibiting ankyrin recruitment. Furthermore, NrCAM phospho-FIGQY levels in the SC were decreased in EphB1/3 and EphB1/2/3 null mice and increased in mutant mice overexpressing constitutively active EphB2 kinase.	SIGNOR-262862
Q13315	Q02880	1	phosphorylation	down-regulates quantity by destabilization	0.411	Specifically, DNA damage signal, triggered by teniposide (VM-26) treatment, activates ATM, cooperating with CK1 to phosphorylate TOP2β on Ser1134 and Ser1130, respectively, in a canonical degron motif to facilitate β-TrCP binding and subsequent degradation.ATM binds with and phosphorylates TOP2β at Ser1134 to promote its degradation by VM-26.	SIGNOR-277510
P31749	P54253	1	phosphorylation	up-regulates quantity by stabilization	0.411	Interaction of Ataxin-1 and 14-3-3 Requires Akt Phosphorylation at S776. 14-3-3 protein, a multifunctional regulatory molecule, mediates the neurotoxicity of ataxin-1 by binding to and stabilizing ataxin-1, thereby slowing its normal degradation.	SIGNOR-252561
P45983	Q16621	1	phosphorylation	down-regulates quantity by destabilization	0.411	Through use of different approaches including nano-scale proteomics, we show that activated-JNK, or Phospho-JNK (P-JNK), physically interacts with p45/NF-E2 and phosphorylates its Ser157 residue. This reaction leads to the poly-ubiquitination of p45/NF-E2 at one or more of six Lys residues, one of which being also a sumoylation site, and its degradation through the proteasome pathway.	SIGNOR-275552
Q8TAP4	Q02577	1	binding	up-regulates activity	0.411	Here we found that LMO3 forms a complex with HEN2 and acts as an upstream mediator for transcription of Mash1 in neuroblastoma.	SIGNOR-254827
P06493	O14757	1	phosphorylation	up-regulates	0.411	Chk1 itself is also subject to cdk-mediated phosphorylation at serines 286 and 301 (s286 and 301). We show that chk1 s301 phosphorylation increases as cells progress through s and g2 and that both cdk1 and cdk2 are likely to contribute to this modification in vivo. We also find that substitution of s286 and s301 with non-phosphorylatable alanine residues strongly attenuates dna damage-induced chk1 activation and g2 checkpoint proficiency	SIGNOR-175071
Q13304	P63096	1	binding	up-regulates activity	0.411	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256692
Q96J02	Q13571	1	polyubiquitination	down-regulates quantity by destabilization	0.411	Here, we found that the level of LAPTM5 protein is regulated negatively by the degradation through ubiquitination by ITCH, an E3 ubiquitin ligase. ITCH directly binds to the PPxY motif of LAPTM5 via its WW domains and promotes ubiquitination through a HECT-type ligase domain.	SIGNOR-272721
P45983	P30307	1	phosphorylation	down-regulates	0.411	Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset.	SIGNOR-164089
P45983	Q9H2B2	1	phosphorylation	up-regulates activity	0.411	JNK phosphorylates Syt 4 at Ser135 in vitro and in vivo.	SIGNOR-273673
P06241	P06239	1	phosphorylation	down-regulates activity	0.411	In nonactivated T cells, CCR7 triggering induced a Fyn dependent phosphorylation of the inhibitory Tyr505 of Lck.\|Inhibiting Fyn in these nonactivated T cells prevented the negative regulation of Lck and facilitated high CCR7 driven T cell chemotaxis.	SIGNOR-279986
Q9BRS8	Q08211	1	binding	up-regulates activity	0.41	La ribonucleoprotein domain family member 6 (LARP6) is the protein that binds 5' SL with high affinity and specificity and coordinates their translation. Here we show that RNA helicase A (RHA) is tethered to the 5' SL of collagen mRNAs by interaction with the C-terminal domain of LARP6.	SIGNOR-273500
Q6ZRS2	P10275	1	binding	up-regulates activity	0.41	The SNF2-related CBP activator protein (SRCAP) serves as a coactivator for several nuclear receptors including the androgen receptor (AR). SRCAP is an ATPase that is the core subunit of a large multiprotein complex and was shown to incorporate the histone variant H2A.Z into nucleosomes. In this report, we demonstrate that SRCAP is expressed in the epithelium of normal prostate and in prostate carcinoma cells, and is associated with AR in the nucleus	SIGNOR-255221
P58753	Q15109	1	binding	up-regulates activity	0.41	These results indicate that TIRAP functions as an essential adaptor protein for RAGE, binding to ligand-activated phosphorylated RAGE and transducing a signal from it.	SIGNOR-280459
Q5TG30	P60953	1	gtpase-activating protein	down-regulates activity	0.41	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260497
P00519	O60674	1	phosphorylation	up-regulates activity	0.41	Jak2 peptide substrate studies indicated that the Bcr-Abl and Abl tyrosine kinases specifically phosphorylated Y1007 of Jak2 but only poorly phosphorylated Y1008. Phosphorylation of Y1007 of Jak2 is known to be critical for its tyrosine kinase activation.	SIGNOR-245365
Q92630	O43255	1	phosphorylation	up-regulates	0.41	In the present study, we identify the serine/threonine kinase dyrk2 as siah2 interaction partner that phosphorylates siah2 at five residues (ser16, thr26, ser28, ser68, and thr119). accordingly, phosphorylated siah2 is more active than the wild-type e3 ligase and shows an increased ability to trigger the hif-1?-Mediated transcriptional response and angiogenesis.	SIGNOR-198729
Q15669	P63000	1	relocalization	down-regulates activity	0.41	Therefore, RhoH functions as a Rac1 antagonist by inhibiting Rac1 translocation to the cell plasma membrane in the regulation of cell migration and F-actin assembly of HPCs	SIGNOR-259085
P42229	Q9P1W9	1	transcriptional regulation	up-regulates quantity by expression	0.41	The results of 2 microarray experiments demonstrated that the aberrant activation of STAT proteins by Flt3-ITDs resulted in the up-regulation of several STAT5-responsive genes, such as Pim-1, Pim-2, and members of the SOCS (suppressor of cytokine signaling) protein family. These results are particularly interesting because recent data point to an important role of Pim kinases in the antiapoptosis of hematopoietic cells.	SIGNOR-249622
P17676	P36956	1	transcriptional regulation	up-regulates quantity	0.41	These results show that GSK3β is involved in regulating phosphorylation and activation of C/EBPβ and that this transcription factor is required to transactivate srebf1a expression, leading to the early steps of adipogenesis	SIGNOR-251645
P35813	Q9UHD2	1	dephosphorylation	down-regulates activity	0.41	Furthermore, PPM1A, but not PPM1B, serves as an efficient phosphatase to dephosphorylate Ser 172 residue of both TBK1 and IKKepsilon kinases, which is critical for their kinase activities.\|In a similar in vitro phosphatase assay, incubation of PPM1A also eliminated TBK1 and IKKepsilon phosphorylation at Ser 172 residue, evidenced by phospho-S172 immunoblotting (XREF_FIG, F and G).\|These observations suggest that PPM1A may block kinase activities of TBK1 and IKKepsilon.	SIGNOR-276966
P00519	Q14191	1	phosphorylation	up-regulates	0.41	We thus hypothesized that wrn may interact with the abl tyrosine kinase in the dna damage response. Here, we provide evidence for a functional and physical interaction between wrn and c-abl, including wrn relocalization in response to dna damage, suggesting that this protein-protein interaction participates in a shared pathway of genome surveillance.	SIGNOR-86497
Q9Y463	P24385	1	phosphorylation	down-regulates	0.41	Further, we found that not only gsk-3beta but also dyrk1b modulates cyclin d1 subcellular localization by the phosphorylation of thr(288). These results suggest that dif-3 induces degradation of cyclin d1 through the gsk-3beta- and dyrk1b-mediated threonine phosphorylation in hela cells	SIGNOR-150126
O15516	P04150	1	transcriptional regulation	down-regulates quantity by repression	0.41	We recently reported that the basic helix-loop- helix transcription factor Clock, which is a histone acetyltransferase and a central component of the self-oscillating transcription factor loop that generates circadian rhythms, represses GR transcriptional activity by acetylating lysine residues within the 'lysine cluster' located in the hinge region of the receptor. This Clock-mediated repression of GR transcriptional activity oscillates in inverse phase to the HPA axis, acting as a target tissue counter-regulatory mechanism to the diurnally fluctuating circulating glucocorticoids.	SIGNOR-253699
Q15831	Q9P0L2	1	phosphorylation	up-regulates	0.41	Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold	SIGNOR-122545
P40424	P15172	1	binding	up-regulates activity	0.41	These domains are necessary for the stable binding of myod to the myogenin promoter through an interaction with an adjacent protein complex containing the homeodomain protein pbx, which appears to be constitutively bound at this site	SIGNOR-124834
P31749	Q92879	1	phosphorylation	up-regulates activity	0.41	In normal myoblasts, Akt kinase phosphorylates CUGBP1 at Ser28 and increases interactions of CUGBP1 with cyclin D1 mRNA.	SIGNOR-280173
P12931	P06733	1	phosphorylation	up-regulates	0.41	The present finding suggested that the tyrosine residue at position 44 in chicken alpha-enolase is the phosphorylation site by the tyrosine kinase. Our data suggest that eno1 was upregulated by caga protein through activating the src and mek/erk signal pathways	SIGNOR-205092
Q13131	Q05469	1	phosphorylation	down-regulates	0.41	Phosphorylation of bovine hormone-sensitive lipase by the amp-activated protein kinase.	SIGNOR-58255
Q15418	O75030	1	phosphorylation	down-regulates	0.41	The current study reveals that c-kit signaling triggers two phosphorylation events on mi, which up-regulate transactivation potential yet simultaneously target mi for ubiquitin-dependent proteolysis. The specific activation/degradation signals derive from mapk/erk targeting of serine 73, whereas serine 409 serves as a substrate for p90 rsk-1. An unphosphorylatable double mutant at these two residues is at once profoundly stable and transcriptionally inert.	SIGNOR-174760
P53350	Q15013	1	phosphorylation	down-regulates activity	0.41	Purified Plk1 bound to p31comet and phosphorylated it, resulting in the suppression of its activity (with TRIP13) to disassemble checkpoint complexes. We conclude that Plk1 phosphorylates p31 on S102 and on five additional sites. The phosphorylation of the additional sites was possibly not detectable in HeLa cell extracts due to the opposing action of protein phosphatases.	SIGNOR-265970
P06493	Q96Q89	1	phosphorylation	up-regulates activity	0.41	Here we report the identification of a novel KRP, termed KRMP1, which undergoes in vivo phosphorylation. The carboxyl-terminal globular tail domain is strongly phosphorylated by mitotic kinase activities almost attributed to cdc2 kinase, which is responsible for phosphorylation on residue Thr-1604 of KRMP1.	SIGNOR-262695
Q13153	Q13418	1	phosphorylation	up-regulates	0.41	We found that pak1 phosphorylates ilk at threonine-173 and serine-246 in vitro and in vivo. together, these results suggest that ilk is a pak1 substrate, undergoes phosphorylation-dependent shuttling between the cell nucleus and cytoplasm, and interacts with gene-regulatory chromatin.	SIGNOR-154303
Q6ZMI3	Q12955	1	relocalization	up-regulates quantity	0.41	Ankyrin-G is recruited to the nodes of Ranvier by gliomedin, which is produced by Schwann cells and accumulates in the perinodal extracellular matrix. As a ligand for neurofascin-186, gliomedin causes the nodal clustering of this cell adhesion molecule, which in turn recruits to the nodal plasma membrane an ankyrin-G protein network consisting of voltage-gated sodium or potassium channels (KCNQ2/3) and β4-spectrin.	SIGNOR-266725
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
P31749	Q969H0	1	phosphorylation	up-regulates activity	0.41	A reciprocal immunoprecipiation with anti-phospho-Akt substrate antibody followed by immunoblotting with anti-FLAG antibodies confirmed these findings (Fig. 1C). We concluded that Fbw7 is phosphorylated at S227 in vivo. Phosphorylation of Fbw7 is required for its biological activity.	SIGNOR-276328
Q9H4B4	O15350	1	phosphorylation	down-regulates activity	0.41	In this study, we found that Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation.\|Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation.	SIGNOR-279647
Q92913	Q14524	1	binding	down-regulates activity	0.41	Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.	SIGNOR-253415
Q8NBJ5	P02452	1	glycosylation	up-regulates activity	0.41	Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.	SIGNOR-261152
P27361	Q03060	1	phosphorylation	down-regulates quantity by destabilization	0.41	The MAPKs extracellular signal-regulated kinases 1 and 2 physically interact with ICER and mediated the phosphorylation of ICER on a critical serine residue (Ser-41). A mutant form of ICER in which Ser-41 was substituted by alanine had a half-life 4-5 h longer than its wild-type counterpart. This alteration in stability was due to the inability of the Ser-41-mutant ICER to be efficiently ubiquitinated and degraded via the ubiquitin-proteasome pathway.	SIGNOR-275978
P49841	Q6R327	1	phosphorylation	down-regulates quantity by destabilization	0.409	We show that this process is dependent on glycogen synthase kinase 3 (GSK3): GSK3 was associated with rictor and directly phosphorylated the Thr-1695 site in a putative CDC4 phospho-degron motif of rictor; mutation of this site impaired the interaction between rictor and FBXW7, decreased rictor ubiquitination, and increased rictor stability.	SIGNOR-276898
P19544	O00592	1	transcriptional regulation	up-regulates quantity by expression	0.409	Binding of WT1 to conserved elements within the Podocalyxin gene promoter results in potent transcriptional activation, and the specific expression pattern of Podocalyxin in the developing kidney mirrors that of WT1 itself.	SIGNOR-252300
Q5TCZ1	Q86UR1	1	binding	up-regulates activity	0.409	Tks4 and Tks5 bind NoxA1 through their SH3 domains in a Rac-independent manner\|NoxO1 is required for full Nox1 and Nox3 oxidase activity at least partially because of its role in the plasma membrane recruitment of the NoxA1 activator protein\|Tks4 and Tks5 support Nox1- and Nox3-dependent ROS generation	SIGNOR-264708
Q13469	Q02078	1	binding	up-regulates	0.409	Upon dephosphorylation by calcineurin, nfatc2, also referred to as nfatp/nfat1, translocates to the nucleus where it directly associates with mef2a and -d. Nfatc2 stimulates mef2-dependent transcription by facilitating recruitment of the p300 coactivator to mef2-response elements.	SIGNOR-117586
P10275	Q13285	1	binding	up-regulates	0.409	Ar suppresses transcription of the lhbeta subunit by interacting with steroidogenic factor-1.	SIGNOR-109996
O43896	P20340	1	relocalization	up-regulates quantity	0.409	Here, we identify Bicaudal-D-related protein 1 (BICDR-1) as an effector of the small GTPase Rab6 and key component of the molecular machinery that controls secretory vesicle transport in developing neurons. BICDR-1 interacts with kinesin motor Kif1C, the dynein/dynactin retrograde motor complex, regulates the pericentrosomal localization of Rab6-positive secretory vesicles and is required for neural development in zebrafish. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation.	SIGNOR-266877
Q13464	P04637	1	phosphorylation	up-regulates quantity	0.409	Besides, ROCK1 phosphorylated p53 at ser15 to up-regulate its protein level.	SIGNOR-280108
Q9NXA8	P48735	1	catalytic activity	up-regulates activity	0.409	Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose-6-phosphate dehydrogenase (G6PD), respectively, and thus activates both NADPH-producing enzymes.	SIGNOR-261212
P15863	P50222	1	binding	up-regulates activity	0.409	We show that Mox1 and Mox2 proteins are capable of interacting with Pax1 and Pax3. We propose that the Mox family of homeodomain proteins participates in the molecular signaling network regulating the diverse events of somite development through the physical interaction with the Pax1 and Pax3 members of the Pax family.	SIGNOR-222232
P36888	P35222	1	phosphorylation	up-regulates activity	0.409	Endogenous beta-catenin co-immunoprecipitated with endogenous activated FLT3, and recombinant activated FLT3 directly phosphorylated recombinant beta-catenin. Finally, FLT3 inhibitor decreased tyrosine phosphorylation of beta-catenin in leukemia cells obtained from FLT3-ITD-positive AML patients. These data demonstrate that FLT3 activation induces beta-catenin tyrosine phosphorylation and nuclear localization, and thus suggest a mechanism for the association of FLT3 activation and beta-catenin oncogeneic signaling in AML.	SIGNOR-260124
Q06124	O43609	1	dephosphorylation	down-regulates	0.409	These results identify sprouty proteins as in vivo targets of corkscrew/shp-2 tyrosine phosphatases and show how corkscrew/shp-2 proteins can promote rtk signaling by inactivating a feedback inhibitor.	SIGNOR-144547
P63211	P19174	1	binding	up-regulates	0.409	Furthermore, this work suggested that the gbetagamma subunits released upon gi activation activated phospholipase c-gamma (plc-gamma) to produce inositol 3 phosphate (ip3) which would subsequently increase intracellular ca2+ abundance.	SIGNOR-199144
Q9NTX7	Q9H2G9	1	ubiquitination	down-regulates quantity by destabilization	0.409	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-263340
P07948	Q7L591	1	phosphorylation	up-regulates activity	0.409	An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling.	SIGNOR-268447
P11802	Q9NS23	1	phosphorylation	down-regulates	0.409	This skp2-dependent destruction of rassf1a requires phosphorylation of the latter on serine-203 by cyclin d-cyclin-dependent kinase 4.	SIGNOR-159849
O00533	Q01484	1	relocalization	up-regulates quantity	0.409	Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.	SIGNOR-266722
P42685	P00533	1	phosphorylation	down-regulates activity	0.409	Furthermore, Rak/Frk inhibited mutant EGFR phosphorylation at an activating site and dramatically decreased the levels of EGFR\u0394747-749/A750P from the plasma membrane.\|Taken together, the results suggest that Rak and Frk inhibits EGFR signaling in cancer cells and has elevated activity against EGFR exon 19 mutants.	SIGNOR-279177
Q96GD4	Q12888	1	phosphorylation	up-regulates activity	0.409	Here we report for the first time that tumor suppressor p53-binding protein 1 (53BP1) is phosphorylated at serine 1342 (S1342) by Aurora kinase B both in vitro and in human cells, which is required for optimal recruitment of 53BP1 at kinetochores.	SIGNOR-264411
P19484	Q14457	1	transcriptional regulation	up-regulates quantity by expression	0.409	As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;	SIGNOR-276558
Q9Y4I1	P60709	1	binding	up-regulates activity	0.409	Myosin Va regulates exocytosis of large dense-core vesicles (LDCVs). interestingly, inhibition of myosin Va potentiates LDCV exocytosis to the same extent as F-actin depolymerization does, suggesting that myosin Va cooperates with the actin cytoskeleton to impede or control LDCV exocytosis	SIGNOR-269280
P68400	Q9Y365	1	phosphorylation	down-regulates	0.409	Interestingly, hypotonic extracts prepared from hek293t cells expressing the serine to alanine mutant exhibited increased lipid transfer activity compared with those from wild-type stard10-expressing cells, suggesting that, in a cellular context, phosphorylation on serine 284 negatively regulates stard10 activity	SIGNOR-155740
Q13976	P26678	1	phosphorylation	up-regulates activity	0.409	Phosphorylation of PLB by PKA or cGKI at Ser 16 relieves the inhibition of SERCA2a and results in increased contractility through enhanced Ca 2+ i reuptake into the SR.	SIGNOR-279269
P12931	Q68CZ2	1	phosphorylation	up-regulates	0.408	Tyrosines in the sh2 domain contribute to the biological activity of tensin-3, and phosphorylation of these tyrosines can regulate ligand binding. tensin-3 is a src substrate	SIGNOR-187843
P42345	Q9P2Y5	1	phosphorylation	up-regulates activity	0.408	MTOR phosphorylates UVRAG at serine 550 and serine 571	SIGNOR-276919
P48454	Q13469	1	dephosphorylation	up-regulates activity	0.408	NFAT1 is phosphorylated on fourteen conserved phosphoserine residues in its regulatory domain, thirteen of which are dephosphorylated upon stimulation. Dephosphorylation of all thirteen residues is required to mask a nuclear export signal (NES), cause full exposure of a nuclear localization signal (NLS), and promote transcriptional activity	SIGNOR-248512
Q13976	Q13507	1	phosphorylation	down-regulates	0.408	The present study demonstrates that human trpc3 expressed in hek293 cells forms store-operated ca2+ influx channels, the activity of which is inhibited by pkg. The inhibition is due to a direct phosphorylation of pkg on trpc3 channels at position t11 and s263.	SIGNOR-142961
Q13976	Q13507-3	1	phosphorylation	down-regulates	0.408	The present study demonstrates that human trpc3 expressed in hek293 cells forms store-operated ca2+ influx channels, the activity of which is inhibited by pkg. The inhibition is due to a direct phosphorylation of pkg on trpc3 channels at position t11 and s263.	SIGNOR-142957
P12931	Q86UR1	1	phosphorylation	up-regulates	0.408	Here, we show that the interaction of noxa1 and tks proteins is dependent on src activity. Interestingly, the abolishment of src-mediated phosphorylation of tyr110 on noxa1 and of tyr508 on tks4 blocks their binding and decreases nox1-dependent ros generation.	SIGNOR-168545
Q00535	P07101	1	phosphorylation	up-regulates activity	0.408	In addition, we demonstrate that co-expression of cdk5 and its regulatory activator p35 with TH increases the stability of TH.\|We show that cdk5 phosphorylates TH at serine 31 and that this phosphorylation is associated with an increase in total TH activity.	SIGNOR-279022
Q9H0H3	Q13541	1	binding	down-regulates quantity by destabilization	0.408	We identified the KLHL25-CUL3 complex as the E3 ubiquitin ligase, which targets hypophosphorylated 4E-BP1. Thus, the activity of eIF4E is under homeostatic control via the regulation of the levels of its repressor protein 4E-BP1 through ubiquitination.	SIGNOR-272049

P27361

Q9NQ66

1

phosphorylation

up-regulates activity

0.412

Plc beta1 could be efficiently phosphorylated by activated mitogen-activated protein kinase but not by pka. The erk phosphorylation site was mapped to serine 982

SIGNOR-106565

P06493

Q8IXJ6

1

phosphorylation

down-regulates

0.412

Here, we demonstrate that sirt2 is phosphorylated both in vitro and in vivo on serine 368 by the cell-cycle regulator, cyclin-dependent kinase 1. Overexpression of sirt2 mediates a delay in cellular proliferation that is dependent on serine 368 phosphorylation.

SIGNOR-154681

P58294

Q8TCW9

1

binding

up-regulates

0.412

The present study demonstrates that eg-vegf/prokineticin 1 and a peptide closely related to eg-vegf, prokineticin 2, are cognate ligands of two orphan g-protein-coupled receptors designated zaq (=eg-vegf/pk-r1) and i5e (=eg-vegf/pk-r2)

SIGNOR-89084

Q9UBI6

P31751

1

binding

up-regulates

0.412

We show that pge2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (g protein) coupled receptor, ep2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase akt by free g protein bg subunits and the direct association of the g protein as subunit with the regulator of g protein signaling (rgs) domain of axin. This leads to the inactivation and release of glycogen synthase kinase 3b from its complex with axin, thereby relieving the inhibitory phosphorylation of b-catenin and activating its signaling pathway.

SIGNOR-141792

P04637

P52789

1

transcriptional regulation

down-regulates quantity by repression

0.412

P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway.

SIGNOR-267466

P52292

O43148

1

binding

down-regulates activity

0.412

KPNA2 Inhibits RNMT Activity|We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor.

SIGNOR-265502

P12931

Q01196

1

phosphorylation

up-regulates activity

0.412

Src phosphorylates Runx1 on one central and four C-terminal tyrosines.|We find that activated Src synergizes with Runx1 to activate a Runx1 luciferase reporter.

SIGNOR-279656

P10523

Q93034

1

binding

up-regulates quantity by stabilization

0.412

Here we report that NEDD4-1, a HECT domain-containing E3 ubiquitin ligase, binds via its HECT domain directly with SAG's C-terminal RING domain and ubiquitylates SAG for proteasome-mediated. We also found that SAG bridges NEDD4-1 via its C-terminus and CUL-5 via its N-terminus to form a NEDD4-1/SAG/CUL-5 tri-complex. Biologically, NEDD4-1 overexpression sensitizes cancer cells to etoposide-induced apoptosis by reducing SAG levels through targeted degradation. Thus, SAG is added to a growing list of NEDD4-1 substrates and mediates its biological function. degradation.

SIGNOR-272844

P00519

O60504

1

phosphorylation

up-regulates activity

0.412

Abl kinase interacts with and phosphorylates vinexin.

SIGNOR-280172

Q13557

Q08289

1

phosphorylation

up-regulates

0.412

We recently identified ca(v)1.2 beta(2a) residues critical for camkii phosphorylation (thr 498) beta(2a) thr 498 and leu 493 are required for ca(v)1.2 activation by camkii in native cells.

SIGNOR-164067

O00533

Q12955

1

relocalization

up-regulates quantity

0.412

Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.

SIGNOR-266723

P42345

Q13322

1

phosphorylation

up-regulates

0.412

The adaptor protein grb10 was identified as an mtorc1 substrate that mediates the phosphoinositide 3-kinase.

SIGNOR-174071

P31749

P09651

1

phosphorylation

down-regulates

0.412

Our data also suggest that akt negatively regulates hnrnp a1-mediated ires activity via phosphorylation at ser199.

SIGNOR-252519

P49841

P41236

1

phosphorylation

up-regulates activity

0.412

Protein phosphatase 1 (PP1) is complexed with inhibitor 2 (I-2) in the cytosol. In rabbit muscle extract PP1.I-2 is activated upon preincubation with ATP/Mg. This activation is caused by phosphorylation of I-2 on Thr(72) by glycogen synthase kinase 3 (GSK3).

SIGNOR-251257

P01106

P06733

2

transcriptional regulation

up-regulates quantity

0.411

C-Myc directly transactivates genes encoding GLUT1, phosphofructokinase, and enolase and increases glucose uptake in Rat1 fibroblasts. Nuclear run-on studies confirmed that the GLUT1 transcriptional rate is elevated by c-Myc. Our findings suggest that overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway.

SIGNOR-259989

P12931

Q15139

1

phosphorylation

up-regulates

0.411

Critical for the regulation of pkd1 activity in response to oxidative stress are src- and abl-mediated tyrosine phosphorylations that eventually lead to protein kinase cdelta (pkcdelta)-mediated activation of pkd1. our data suggest that pkd1 phosphorylation at tyr95 generates a binding motif for pkcdelta, and that oxidative stress-mediated pkcdelta/pkd interaction results in pkd1 activation loop phosphorylation and activation.

SIGNOR-157716

P20309

O95837

1

binding

up-regulates activity

0.411

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

SIGNOR-257134

Q13627

Q14814

1

phosphorylation

down-regulates activity

0.411

DYRK1A phosphorylates MEF2D and decreases its transcriptional activity

SIGNOR-277901

Q9Y2K2

P56524

1

phosphorylation

down-regulates activity

0.411

They find that SIK3 phosphorylates and inhibits HDAC4 during feeding states.|They find that SIK3 phosphorylates and inhibits HDAC4 during feeding\nstates.

SIGNOR-279430

P43657

P50148

1

binding

up-regulates

0.411

Lysophosphatidic acid (lpa), a major g protein coupled receptor (gpcr)-activating ligand present in serum, elicits growth factor like responses by stimulating specific gpcrs coupled to heterotrimeric g proteins such as g(i), g(q), and g12/13.

SIGNOR-135822

P31629

P30874

1

transcriptional regulation

up-regulates quantity by expression

0.411

Activation of somatostatin receptor II expression by transcription factors MIBP1 and SEF-2 in the murine brain.

SIGNOR-261617

O96017

Q13263

1

phosphorylation

down-regulates activity

0.411

In particular, Chk2 phosphorylates KAP1 on Ser473 decreasing the interaction between KAP1 and HP1 proteins: this post translational modification promotes HP1\u03b2 mobilization and the reorganization of chromatin structure favoring the repair of DNA breaks inside heterochromatin [ , ].|Of note, phosphorylation of S473 by Chk2 decreases the interaction between KAP1 and HP1 proteins and is necessary for HP1\u03b2 mobilization, a key event for DNA repair in the heterochromatin [ - ].

SIGNOR-279730

P06733

P01106

2

transcriptional regulation

down-regulates quantity by repression

0.411

This result suggests that MBP-1 in vivo acts as a sequence-specific repressor.

SIGNOR-261594

P35240

Q13043

1

binding

up-regulates activity

0.411

NF2 is activated by oxidative stress in cardiomyocytes and mouse myocardium and facilitates apoptosis. NF2 promotes I/R injury through activation of Mst1 and inhibition of Yap, thereby regulating Hippo signaling in the adult heart.

SIGNOR-261956

Q96Q15

P04637

1

phosphorylation

up-regulates

0.411

Hsmg-1 is a stress-activated kinase that phosphorylates p53 and hupf1 in vitrothe observation that hsmg-1 exhibits p53 (ser-15) kinase activity in vitro suggested that this pikk might be involved in genotoxic stress-induced p53 phosphorylation and stabilization in intact cells.

SIGNOR-125135

P49840

P13807

1

phosphorylation

down-regulates

0.411

Glycogen synthase kinase-3 (gsk-3) phosphorylates four serine residues in the cooh terminus of glycogen synthase. Phosphorylation of one of these residues, ser640 (site 3a), causes strong inactivation of glycogen synthase

SIGNOR-118927

Q5S007

P15311

1

phosphorylation

up-regulates activity

0.411

LRRK2 also phosphorylated ezrin and radixin, which are related to moesin, at the residue equivalent to Thr558, as well as a peptide (LRRKtide: RLGRDKYKTLRQIRQ) encompassing Thr558.

SIGNOR-279202

P24941

P33981

1

phosphorylation

up-regulates quantity by stabilization

0.411

Cdk2 phosphorylates Mps1 at T468, attenuating the function of a degradation signal found in amino acids 420\u2013507 (encoded by exons 12 and 13) and allowing the accumulation of a centrosomal pool of Mps1 that represents no more than 10% of total cellular Mps1 ( xref ).

SIGNOR-279398

Q15011

P11021

1

relocalization

up-regulates quantity by stabilization

0.411

A key inhibitor of the turnover and Nt-arginylation of BiP was HERP (homocysteine-responsive ER protein), a 43-kDa ER membrane-integrated protein that is an essential component of ER-associated protein degradation.

SIGNOR-261346

Q9P278

P07900

1

binding

down-regulates activity

0.411

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-261414

P54762

Q92823

1

phosphorylation

up-regulates activity

0.411

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

SIGNOR-262862

Q13315

Q02880

1

phosphorylation

down-regulates quantity by destabilization

0.411

Specifically, DNA damage signal, triggered by teniposide (VM-26) treatment, activates ATM, cooperating with CK1 to phosphorylate TOP2β on Ser1134 and Ser1130, respectively, in a canonical degron motif to facilitate β-TrCP binding and subsequent degradation.ATM binds with and phosphorylates TOP2β at Ser1134 to promote its degradation by VM-26.

SIGNOR-277510

P31749

P54253

1

phosphorylation

up-regulates quantity by stabilization

0.411

Interaction of Ataxin-1 and 14-3-3 Requires Akt Phosphorylation at S776. 14-3-3 protein, a multifunctional regulatory molecule, mediates the neurotoxicity of ataxin-1 by binding to and stabilizing ataxin-1, thereby slowing its normal degradation.

SIGNOR-252561

P45983

Q16621

1

phosphorylation

down-regulates quantity by destabilization

0.411

Through use of different approaches including nano-scale proteomics, we show that activated-JNK, or Phospho-JNK (P-JNK), physically interacts with p45/NF-E2 and phosphorylates its Ser157 residue. This reaction leads to the poly-ubiquitination of p45/NF-E2 at one or more of six Lys residues, one of which being also a sumoylation site, and its degradation through the proteasome pathway.

SIGNOR-275552

Q8TAP4

Q02577

1

binding

up-regulates activity

0.411

Here we found that LMO3 forms a complex with HEN2 and acts as an upstream mediator for transcription of Mash1 in neuroblastoma.

SIGNOR-254827

P06493

O14757

1

phosphorylation

up-regulates

0.411

Chk1 itself is also subject to cdk-mediated phosphorylation at serines 286 and 301 (s286 and 301). We show that chk1 s301 phosphorylation increases as cells progress through s and g2 and that both cdk1 and cdk2 are likely to contribute to this modification in vivo. We also find that substitution of s286 and s301 with non-phosphorylatable alanine residues strongly attenuates dna damage-induced chk1 activation and g2 checkpoint proficiency

SIGNOR-175071

Q13304

P63096

1

binding

up-regulates activity

0.411

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

SIGNOR-256692

Q96J02

Q13571

1

polyubiquitination

down-regulates quantity by destabilization

0.411

Here, we found that the level of LAPTM5 protein is regulated negatively by the degradation through ubiquitination by ITCH, an E3 ubiquitin ligase. ITCH directly binds to the PPxY motif of LAPTM5 via its WW domains and promotes ubiquitination through a HECT-type ligase domain.

SIGNOR-272721

P45983

P30307

1

phosphorylation

down-regulates

0.411

Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset.

SIGNOR-164089

P45983

Q9H2B2

1

phosphorylation

up-regulates activity

0.411

JNK phosphorylates Syt 4 at Ser135 in vitro and in vivo.

SIGNOR-273673

P06241

P06239

1

phosphorylation

down-regulates activity

0.411

In nonactivated T cells, CCR7 triggering induced a Fyn dependent phosphorylation of the inhibitory Tyr505 of Lck.|Inhibiting Fyn in these nonactivated T cells prevented the negative regulation of Lck and facilitated high CCR7 driven T cell chemotaxis.

SIGNOR-279986

Q9BRS8

Q08211

1

binding

up-regulates activity

0.41

La ribonucleoprotein domain family member 6 (LARP6) is the protein that binds 5' SL with high affinity and specificity and coordinates their translation. Here we show that RNA helicase A (RHA) is tethered to the 5' SL of collagen mRNAs by interaction with the C-terminal domain of LARP6.

SIGNOR-273500

Q6ZRS2

P10275

1

binding

up-regulates activity

0.41

The SNF2-related CBP activator protein (SRCAP) serves as a coactivator for several nuclear receptors including the androgen receptor (AR). SRCAP is an ATPase that is the core subunit of a large multiprotein complex and was shown to incorporate the histone variant H2A.Z into nucleosomes. In this report, we demonstrate that SRCAP is expressed in the epithelium of normal prostate and in prostate carcinoma cells, and is associated with AR in the nucleus

SIGNOR-255221

P58753

Q15109

1

binding

up-regulates activity

0.41

These results indicate that TIRAP functions as an essential adaptor protein for RAGE, binding to ligand-activated phosphorylated RAGE and transducing a signal from it.

SIGNOR-280459

Q5TG30

P60953

1

gtpase-activating protein

down-regulates activity

0.41

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260497

P00519

O60674

1

phosphorylation

up-regulates activity

0.41

Jak2 peptide substrate studies indicated that the Bcr-Abl and Abl tyrosine kinases specifically phosphorylated Y1007 of Jak2 but only poorly phosphorylated Y1008. Phosphorylation of Y1007 of Jak2 is known to be critical for its tyrosine kinase activation.

SIGNOR-245365

Q92630

O43255

1

phosphorylation

up-regulates

0.41

In the present study, we identify the serine/threonine kinase dyrk2 as siah2 interaction partner that phosphorylates siah2 at five residues (ser16, thr26, ser28, ser68, and thr119). accordingly, phosphorylated siah2 is more active than the wild-type e3 ligase and shows an increased ability to trigger the hif-1?-Mediated transcriptional response and angiogenesis.

SIGNOR-198729

Q15669

P63000

1

relocalization

down-regulates activity

0.41

Therefore, RhoH functions as a Rac1 antagonist by inhibiting Rac1 translocation to the cell plasma membrane in the regulation of cell migration and F-actin assembly of HPCs

SIGNOR-259085

P42229

Q9P1W9

1

transcriptional regulation

up-regulates quantity by expression

0.41

The results of 2 microarray experiments demonstrated that the aberrant activation of STAT proteins by Flt3-ITDs resulted in the up-regulation of several STAT5-responsive genes, such as Pim-1, Pim-2, and members of the SOCS (suppressor of cytokine signaling) protein family. These results are particularly interesting because recent data point to an important role of Pim kinases in the antiapoptosis of hematopoietic cells.

SIGNOR-249622

P17676

P36956

1

transcriptional regulation

up-regulates quantity

0.41

These results show that GSK3β is involved in regulating phosphorylation and activation of C/EBPβ and that this transcription factor is required to transactivate srebf1a expression, leading to the early steps of adipogenesis

SIGNOR-251645

P35813

Q9UHD2

1

dephosphorylation

down-regulates activity

0.41

Furthermore, PPM1A, but not PPM1B, serves as an efficient phosphatase to dephosphorylate Ser 172 residue of both TBK1 and IKKepsilon kinases, which is critical for their kinase activities.|In a similar in vitro phosphatase assay, incubation of PPM1A also eliminated TBK1 and IKKepsilon phosphorylation at Ser 172 residue, evidenced by phospho-S172 immunoblotting (XREF_FIG, F and G).|These observations suggest that PPM1A may block kinase activities of TBK1 and IKKepsilon.

SIGNOR-276966

P00519

Q14191

1

phosphorylation

up-regulates

0.41

We thus hypothesized that wrn may interact with the abl tyrosine kinase in the dna damage response. Here, we provide evidence for a functional and physical interaction between wrn and c-abl, including wrn relocalization in response to dna damage, suggesting that this protein-protein interaction participates in a shared pathway of genome surveillance.

SIGNOR-86497

Q9Y463

P24385

1

phosphorylation

down-regulates

0.41

Further, we found that not only gsk-3beta but also dyrk1b modulates cyclin d1 subcellular localization by the phosphorylation of thr(288). These results suggest that dif-3 induces degradation of cyclin d1 through the gsk-3beta- and dyrk1b-mediated threonine phosphorylation in hela cells

SIGNOR-150126

O15516

P04150

1

transcriptional regulation

down-regulates quantity by repression

0.41

We recently reported that the basic helix-loop- helix transcription factor Clock, which is a histone acetyltransferase and a central component of the self-oscillating transcription factor loop that generates circadian rhythms, represses GR transcriptional activity by acetylating lysine residues within the 'lysine cluster' located in the hinge region of the receptor. This Clock-mediated repression of GR transcriptional activity oscillates in inverse phase to the HPA axis, acting as a target tissue counter-regulatory mechanism to the diurnally fluctuating circulating glucocorticoids.

SIGNOR-253699

Q15831

Q9P0L2

1

phosphorylation

up-regulates

0.41

Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold

SIGNOR-122545

P40424

P15172

1

binding

up-regulates activity

0.41

These domains are necessary for the stable binding of myod to the myogenin promoter through an interaction with an adjacent protein complex containing the homeodomain protein pbx, which appears to be constitutively bound at this site

SIGNOR-124834

P31749

Q92879

1

phosphorylation

up-regulates activity

0.41

In normal myoblasts, Akt kinase phosphorylates CUGBP1 at Ser28 and increases interactions of CUGBP1 with cyclin D1 mRNA.

SIGNOR-280173

P12931

P06733

1

phosphorylation

up-regulates

0.41

The present finding suggested that the tyrosine residue at position 44 in chicken alpha-enolase is the phosphorylation site by the tyrosine kinase. Our data suggest that eno1 was upregulated by caga protein through activating the src and mek/erk signal pathways

SIGNOR-205092

Q13131

Q05469

1

phosphorylation

down-regulates

0.41

Phosphorylation of bovine hormone-sensitive lipase by the amp-activated protein kinase.

SIGNOR-58255

Q15418

O75030

1

phosphorylation

down-regulates

0.41

The current study reveals that c-kit signaling triggers two phosphorylation events on mi, which up-regulate transactivation potential yet simultaneously target mi for ubiquitin-dependent proteolysis. The specific activation/degradation signals derive from mapk/erk targeting of serine 73, whereas serine 409 serves as a substrate for p90 rsk-1. An unphosphorylatable double mutant at these two residues is at once profoundly stable and transcriptionally inert.

SIGNOR-174760

P53350

Q15013

1

phosphorylation

down-regulates activity

0.41

Purified Plk1 bound to p31comet and phosphorylated it, resulting in the suppression of its activity (with TRIP13) to disassemble checkpoint complexes. We conclude that Plk1 phosphorylates p31 on S102 and on five additional sites. The phosphorylation of the additional sites was possibly not detectable in HeLa cell extracts due to the opposing action of protein phosphatases.

SIGNOR-265970

P06493

Q96Q89

1

phosphorylation

up-regulates activity

0.41

Here we report the identification of a novel KRP, termed KRMP1, which undergoes in vivo phosphorylation. The carboxyl-terminal globular tail domain is strongly phosphorylated by mitotic kinase activities almost attributed to cdc2 kinase, which is responsible for phosphorylation on residue Thr-1604 of KRMP1.

SIGNOR-262695

Q13153

Q13418

1

phosphorylation

up-regulates

0.41

We found that pak1 phosphorylates ilk at threonine-173 and serine-246 in vitro and in vivo. together, these results suggest that ilk is a pak1 substrate, undergoes phosphorylation-dependent shuttling between the cell nucleus and cytoplasm, and interacts with gene-regulatory chromatin.

SIGNOR-154303

Q6ZMI3

Q12955

1

relocalization

up-regulates quantity

0.41

Ankyrin-G is recruited to the nodes of Ranvier by gliomedin, which is produced by Schwann cells and accumulates in the perinodal extracellular matrix. As a ligand for neurofascin-186, gliomedin causes the nodal clustering of this cell adhesion molecule, which in turn recruits to the nodal plasma membrane an ankyrin-G protein network consisting of voltage-gated sodium or potassium channels (KCNQ2/3) and β4-spectrin.

SIGNOR-266725

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

P31749

Q969H0

1

phosphorylation

up-regulates activity

0.41

A reciprocal immunoprecipiation with anti-phospho-Akt substrate antibody followed by immunoblotting with anti-FLAG antibodies confirmed these findings (Fig. 1C). We concluded that Fbw7 is phosphorylated at S227 in vivo. Phosphorylation of Fbw7 is required for its biological activity.

SIGNOR-276328

Q9H4B4

O15350

1

phosphorylation

down-regulates activity

0.41

In this study, we found that Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation.|Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation.

SIGNOR-279647

Q92913

Q14524

1

binding

down-regulates activity

0.41

Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.

SIGNOR-253415

Q8NBJ5

P02452

1

glycosylation

up-regulates activity

0.41

Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.

SIGNOR-261152

P27361

Q03060

1

phosphorylation

down-regulates quantity by destabilization

0.41

The MAPKs extracellular signal-regulated kinases 1 and 2 physically interact with ICER and mediated the phosphorylation of ICER on a critical serine residue (Ser-41). A mutant form of ICER in which Ser-41 was substituted by alanine had a half-life 4-5 h longer than its wild-type counterpart. This alteration in stability was due to the inability of the Ser-41-mutant ICER to be efficiently ubiquitinated and degraded via the ubiquitin-proteasome pathway.

SIGNOR-275978

P49841

Q6R327

1

phosphorylation

down-regulates quantity by destabilization

0.409

We show that this process is dependent on glycogen synthase kinase 3 (GSK3): GSK3 was associated with rictor and directly phosphorylated the Thr-1695 site in a putative CDC4 phospho-degron motif of rictor; mutation of this site impaired the interaction between rictor and FBXW7, decreased rictor ubiquitination, and increased rictor stability.

SIGNOR-276898

P19544

O00592

1

transcriptional regulation

up-regulates quantity by expression

0.409

Binding of WT1 to conserved elements within the Podocalyxin gene promoter results in potent transcriptional activation, and the specific expression pattern of Podocalyxin in the developing kidney mirrors that of WT1 itself.

SIGNOR-252300

Q5TCZ1

Q86UR1

1

binding

up-regulates activity

0.409

Tks4 and Tks5 bind NoxA1 through their SH3 domains in a Rac-independent manner|NoxO1 is required for full Nox1 and Nox3 oxidase activity at least partially because of its role in the plasma membrane recruitment of the NoxA1 activator protein|Tks4 and Tks5 support Nox1- and Nox3-dependent ROS generation

SIGNOR-264708

Q13469

Q02078

1

binding

up-regulates

0.409

Upon dephosphorylation by calcineurin, nfatc2, also referred to as nfatp/nfat1, translocates to the nucleus where it directly associates with mef2a and -d. Nfatc2 stimulates mef2-dependent transcription by facilitating recruitment of the p300 coactivator to mef2-response elements.

SIGNOR-117586

P10275

Q13285

1

binding

up-regulates

0.409

Ar suppresses transcription of the lhbeta subunit by interacting with steroidogenic factor-1.

SIGNOR-109996

O43896

P20340

1

relocalization

up-regulates quantity

0.409

Here, we identify Bicaudal-D-related protein 1 (BICDR-1) as an effector of the small GTPase Rab6 and key component of the molecular machinery that controls secretory vesicle transport in developing neurons. BICDR-1 interacts with kinesin motor Kif1C, the dynein/dynactin retrograde motor complex, regulates the pericentrosomal localization of Rab6-positive secretory vesicles and is required for neural development in zebrafish. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation.

SIGNOR-266877

Q13464

P04637

1

phosphorylation

up-regulates quantity

0.409

Besides, ROCK1 phosphorylated p53 at ser15 to up-regulate its protein level.

SIGNOR-280108

Q9NXA8

P48735

1

catalytic activity

up-regulates activity

0.409

Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose-6-phosphate dehydrogenase (G6PD), respectively, and thus activates both NADPH-producing enzymes.

SIGNOR-261212

P15863

P50222

1

binding

up-regulates activity

0.409

We show that Mox1 and Mox2 proteins are capable of interacting with Pax1 and Pax3. We propose that the Mox family of homeodomain proteins participates in the molecular signaling network regulating the diverse events of somite development through the physical interaction with the Pax1 and Pax3 members of the Pax family.

SIGNOR-222232

P36888

P35222

1

phosphorylation

up-regulates activity

0.409

Endogenous beta-catenin co-immunoprecipitated with endogenous activated FLT3, and recombinant activated FLT3 directly phosphorylated recombinant beta-catenin. Finally, FLT3 inhibitor decreased tyrosine phosphorylation of beta-catenin in leukemia cells obtained from FLT3-ITD-positive AML patients. These data demonstrate that FLT3 activation induces beta-catenin tyrosine phosphorylation and nuclear localization, and thus suggest a mechanism for the association of FLT3 activation and beta-catenin oncogeneic signaling in AML.

SIGNOR-260124

Q06124

O43609

1

dephosphorylation

down-regulates

0.409

These results identify sprouty proteins as in vivo targets of corkscrew/shp-2 tyrosine phosphatases and show how corkscrew/shp-2 proteins can promote rtk signaling by inactivating a feedback inhibitor.

SIGNOR-144547

P63211

P19174

1

binding

up-regulates

0.409

Furthermore, this work suggested that the gbetagamma subunits released upon gi activation activated phospholipase c-gamma (plc-gamma) to produce inositol 3 phosphate (ip3) which would subsequently increase intracellular ca2+ abundance.

SIGNOR-199144

Q9NTX7

Q9H2G9

1

ubiquitination

down-regulates quantity by destabilization

0.409

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-263340

P07948

Q7L591

1

phosphorylation

up-regulates activity

0.409

An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling.

SIGNOR-268447

P11802

Q9NS23

1

phosphorylation

down-regulates

0.409

This skp2-dependent destruction of rassf1a requires phosphorylation of the latter on serine-203 by cyclin d-cyclin-dependent kinase 4.

SIGNOR-159849

O00533

Q01484

1

relocalization

up-regulates quantity

0.409

Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.

SIGNOR-266722

P42685

P00533

1

phosphorylation

down-regulates activity

0.409

Furthermore, Rak/Frk inhibited mutant EGFR phosphorylation at an activating site and dramatically decreased the levels of EGFR\u0394747-749/A750P from the plasma membrane.|Taken together, the results suggest that Rak and Frk inhibits EGFR signaling in cancer cells and has elevated activity against EGFR exon 19 mutants.

SIGNOR-279177

Q96GD4

Q12888

1

phosphorylation

up-regulates activity

0.409

Here we report for the first time that tumor suppressor p53-binding protein 1 (53BP1) is phosphorylated at serine 1342 (S1342) by Aurora kinase B both in vitro and in human cells, which is required for optimal recruitment of 53BP1 at kinetochores.

SIGNOR-264411

P19484

Q14457

1

transcriptional regulation

up-regulates quantity by expression

0.409

As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;

SIGNOR-276558

Q9Y4I1

P60709

1

binding

up-regulates activity

0.409

Myosin Va regulates exocytosis of large dense-core vesicles (LDCVs). interestingly, inhibition of myosin Va potentiates LDCV exocytosis to the same extent as F-actin depolymerization does, suggesting that myosin Va cooperates with the actin cytoskeleton to impede or control LDCV exocytosis

SIGNOR-269280

P68400

Q9Y365

1

phosphorylation

down-regulates

0.409

Interestingly, hypotonic extracts prepared from hek293t cells expressing the serine to alanine mutant exhibited increased lipid transfer activity compared with those from wild-type stard10-expressing cells, suggesting that, in a cellular context, phosphorylation on serine 284 negatively regulates stard10 activity

SIGNOR-155740

Q13976

P26678

1

phosphorylation

up-regulates activity

0.409

Phosphorylation of PLB by PKA or cGKI at Ser 16 relieves the inhibition of SERCA2a and results in increased contractility through enhanced Ca 2+ i reuptake into the SR.

SIGNOR-279269

P12931

Q68CZ2

1

phosphorylation

up-regulates

0.408

Tyrosines in the sh2 domain contribute to the biological activity of tensin-3, and phosphorylation of these tyrosines can regulate ligand binding. tensin-3 is a src substrate

SIGNOR-187843

P42345

Q9P2Y5

1

phosphorylation

up-regulates activity

0.408

MTOR phosphorylates UVRAG at serine 550 and serine 571

SIGNOR-276919

P48454

Q13469

1

dephosphorylation

up-regulates activity

0.408

NFAT1 is phosphorylated on fourteen conserved phosphoserine residues in its regulatory domain, thirteen of which are dephosphorylated upon stimulation. Dephosphorylation of all thirteen residues is required to mask a nuclear export signal (NES), cause full exposure of a nuclear localization signal (NLS), and promote transcriptional activity

SIGNOR-248512

Q13976

Q13507

1

phosphorylation

down-regulates

0.408

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

SIGNOR-142961

Q13976

Q13507-3

1

phosphorylation

down-regulates

0.408

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

SIGNOR-142957

P12931

Q86UR1

1

phosphorylation

up-regulates

0.408

Here, we show that the interaction of noxa1 and tks proteins is dependent on src activity. Interestingly, the abolishment of src-mediated phosphorylation of tyr110 on noxa1 and of tyr508 on tks4 blocks their binding and decreases nox1-dependent ros generation.

SIGNOR-168545

Q00535

P07101

1

phosphorylation

up-regulates activity

0.408

In addition, we demonstrate that co-expression of cdk5 and its regulatory activator p35 with TH increases the stability of TH.|We show that cdk5 phosphorylates TH at serine 31 and that this phosphorylation is associated with an increase in total TH activity.

SIGNOR-279022

Q9H0H3

Q13541

1

binding

down-regulates quantity by destabilization

0.408

We identified the KLHL25-CUL3 complex as the E3 ubiquitin ligase, which targets hypophosphorylated 4E-BP1. Thus, the activity of eIF4E is under homeostatic control via the regulation of the levels of its repressor protein 4E-BP1 through ubiquitination.

SIGNOR-272049