GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P43403	Q9UQQ2	1	phosphorylation	up-regulates	0.363	In vitro tyrosine phosphorylation of lnk by lck and zap-70. Tyrosine 297 would appear to be an attractive target for phosphorylation within the c-terminal domain. Our studies suggest that although lnk may participate in tcr signaling, its functions are in no way limiting during t cell development or activation.	SIGNOR-48854
P00742	P01008	0	cleavage	down-regulates activity	0.877	Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1	SIGNOR-264138
P07585	P08254	0	cleavage	down-regulates quantity by destabilization	0.673	Degradation of decorin by matrix metalloproteinases. These data indicate proteolytic degradation of DCN by MMP-2, MMP-3 and MMP-7, and suggest the possibility that, under pathophysiological conditions, the digestion by the MMPs may induce tissue reactions mediated by TGF-beta1 released from DCN in the connective tissues.	SIGNOR-256353
P54646	Q13085	1	phosphorylation	down-regulates	0.697	Significant negative linear correlations between phospho-acc and acc activity were observed in all models (p < 0.01). The decline in acc activity was related to the decrease in pcr and the rise in amp. A relationship between phospho-ampk (threonine 172) and activity of ampk immunoprecipitated with anti-alpha(2) subunit antibody preparation was also observed.	SIGNOR-87583
P55212	P49768	1	cleavage	up-regulates activity	0.372	Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.	SIGNOR-261753
Q6A1A2	P31749	1	phosphorylation	up-regulates	0.2	Akt to the plasma membrane where it is phosphorylated and activated by phosphoinositide-dependent kinase (pdk) 1 and pdk2.	SIGNOR-252628
Q14289	O43294	1	phosphorylation	up-regulates activity	0.71	Hic-5 is a CAKbeta-binding protein localized at focal adhesions. Here we show that overexpression of CAKbeta or Fyn, but not FAK, enhanced the tyrosine phosphorylation of coexpressed Hic-5 in COS-7 cells. The Y60F mutant of Hic-5 was not phosphorylated, and Hic-5 phosphorylated on tyrosine 60 was bound specifically to the SH2 domain of Csk. Specific phosphorylation of Hic-5 by CAKbeta and Fyn may activate a signaling pathway mediated by Hic-5.	SIGNOR-262876
O75604	P37173	0	phosphorylation	up-regulates activity	0.2	Here, we report the role of USP2a in promoting metastasis by facilitating TGF-β-triggered signaling. USP2a interacts with TGFBR1 and TGFBR2 upon TGF-β stimulation and removes K33-linked polyubiquitin chains from Lys502 of TGFBR1, promoting the recruitment of SMAD2/3. Simultaneously, TGFBR2 phosphorylates Ser207/Ser225 of USP2a, leading to the disassociation of SMAD2/3 from TGFBR1.	SIGNOR-273604
Q9H9S0	P27361	0	phosphorylation	down-regulates	0.492	We found that activation of ERK1 signaling inhibited transactivation activity of Nanog.\|We showed the direct phosphorylation of Nanog by ERK1 and clearly showed that Ser52 is the major phosphorylation site and Ser65 is weakly phosphorylated by ERK1.	SIGNOR-278487
P23771	Q9UI32	1	transcriptional regulation	up-regulates quantity by expression	0.332	Thus, GATA3 contributes to the elevated expression of GLS2 in luminal-subtype breast cancers.	SIGNOR-268034
P42224	P33076	1	transcriptional regulation	up-regulates	0.539	When IFN-γ binds to its receptor, the receptor-associated protein tyrosine kinases Janus kinase I (JAK1) and JAK2 are activated (37). This leads to the phosphorylation of STAT1, which then dimerizes, translocates to the nucleus, and activates its target promoters, including the pIV promoter of Ciita	SIGNOR-256249
Q13485	Q9UNE7	0	polyubiquitination	down-regulates quantity by destabilization	0.396	We demonstrate that the coexpression of Smad1 and Smad4 with the CHIP protein results in the degradation of the Smad proteins through a ubiquitin-mediated process.	SIGNOR-272947
P49841	Q9BYG3	1	phosphorylation	up-regulates activity	0.2	The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. phosphorylation of Thr234 by GSK3 proceeds only after Thr238 is already phosphorylated by CDK1.	SIGNOR-262698
P11274	P01106	0	transcriptional regulation	up-regulates quantity by expression	0.362	In the present study we demonstrate that MYC and its partner MAX bind to the BCR promoter, leading to up-regulation of BCR and BCR/ABL1 at both transcriptional and protein levels.\|Here we describe a regulatory pathway modulating BCR and BCR/ABL1 expression, showing that the BCR promoter is under the transcriptional control of the MYC/MAX heterodimer.	SIGNOR-272144
O60566	O14757	0	phosphorylation	up-regulates activity	0.447	Nonetheless, in our experimental system a Chk1-dependent BubR1 phosphorylation was also observed after Noc treatment.\|Possible requirement of Chk1 in U2OS cells to activate the mitotic spindle checkpoint proteins Mad2 and BubR1.	SIGNOR-280223
P09629	P68400	0	phosphorylation	down-regulates activity	0.344	Thus, we concluded that CKII can phosphorylate HOXB7 in vitro and that this phosphorylation occurs at both of the CKII target sites, S133 and T204. \| Wild-type HOXB7 inhibited the differentiation of 32D cells, whereas mutations in the Pbx-binding pentapeptide motif or the DNA-binding homeodomain, as well as internal deletions of the N-terminal unique region, blocked this effect. Interestingly, mutations eliminating two target sites for casein kinase II, the glutamate-rich C terminus, or the first 14 amino acids of HOXB7, led to enhanced 32D differentiation.	SIGNOR-250896
P45983	Q5JR12	1	phosphorylation	down-regulates	0.344	Specific phosphorylation of pp2czeta at ser (92) by stress-activated jnk attenuates its phosphatase activity in cells.	SIGNOR-178930
Q96BR1	P49815	1	phosphorylation	up-regulates activity	0.434	SGK3 phosphorylates six sites on TSC2 to activate mTORC1 in an AKT-independent manner.	SIGNOR-279284
O00429	Q9BXM7	0	phosphorylation	up-regulates activity	0.6	We here demonstrate that PINK1 directly phosphorylates Drp1 on S616.	SIGNOR-279548
Q13144	P05198	1	guanine nucleotide exchange factor	up-regulates activity	0.84	EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.	SIGNOR-269123
Q9ULV8	P07949	1	ubiquitination	down-regulates quantity by destabilization	0.368	Here we show that Cbl-c binds wild-type and MEN2A isoforms of the receptor tyrosine kinase, RET, and that Cbl-c enhances ubiquitination and degradation of activated RET.\|We show that Cbl-c negatively regulates RET by ubiquitinating and downregulating the activated RTK while Enigma positively regulates activated RET by preventing Cbl-c binding to RET and thus preventing RET ubiquitination and degradation while promoting RET mitogenic signaling.	SIGNOR-278674
Q14790	Q7Z434	0	relocalization	up-regulates	0.587	Another protein suggested to play a role in caspase-8 translocation to mitochondria is the mitochondrial membrane protein cardif	SIGNOR-143572
Q13705	P36896	1	phosphorylation	up-regulates activity	0.691	Activin binds directly to ActR-IIB, and this complex associates with ActR-IB, which does not bind ligand on its own. In the resulting complex, ActR-IB becomes hyperphosphorylated, and this requires the kinase activity of ActR-IIB.	SIGNOR-235146
Q9H0H5	P63000	1	gtpase-activating protein	down-regulates activity	0.586	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-260512
P17612	O00141	1	phosphorylation	up-regulates activity	0.297	In this publication, we demonstrate that cAMP can activate Sgk and that this effect is mediated by PKA, which directly phosphorylates Thr369 in Sgk.	SIGNOR-275972
Q9UHD2	O15379	1	phosphorylation	up-regulates activity	0.2	The feedback of activation of HDAC3 by TBK1 was able to further enhance IFN production and IFN-STAT activation.\|We found that HDAC3 could be phosphorylated by TBK1.	SIGNOR-279662
P28482	P08235	1	phosphorylation	down-regulates quantity by destabilization	0.286	Taken together, these data suggest that ERK1/2 directly phosphorylates the MR on several serine residues present in its NTD, that the upward shift of MR is mainly due to receptor phosphorylation, and finally that these sites represent the major aldosterone-inducible targets for MR phosphorylation.MR phosphorylation limits the transcriptional activity.Taken together, these results provide evidence that MR phosphorylation plays a role in aldosterone-mediated ubiquitylation and degradation.	SIGNOR-276101
Q8TDR2	Q05D32	0	dephosphorylation	up-regulates quantity by stabilization	0.282	We found that peptides corresponding to phosphoserines 194 and 216 of PDIK1L (S385 and S413 of STK35) were efficiently dephosphorylated by SCP4, whereas no activity was detected for the other two phosphopeptides (Figure 6D).	SIGNOR-273775
P34947	P08235	1	phosphorylation	down-regulates	0.26	We report that GRK5 phosphorylates and inhibits the cardiac MR whereas GRK2 phosphorylates and desensitizes GPER.	SIGNOR-278478
P35222	P23471	0	dephosphorylation	up-regulates activity	0.378	PTPRZ1 constitutively promotes the tyrosine dephosphorylation of \u03b2-catenin, and thus \u03b2-catenin participation in TCF-mediated transcription.	SIGNOR-277044
P28482	Q13586	1	phosphorylation	up-regulates	0.351	The netrin-2-mediated nfatc3 activation was coincident with robust interactions between cdo and stim1 in myoblasts and the erk-mediated stim1 phosphorylation at serine 575	SIGNOR-192788
P52789	P04637	0	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
P68400	P54274	1	phosphorylation	up-regulates	0.2	Regulation of telomeric repeat binding factor 1 binding to telomeres by casein kinase 2-mediated phosphorylation. Mapping of the ck2 target site identified threonine 122 as a substrate in trf1. A threonine to alanine change at this position led to a diminished dna binding due to reduced dimerization of trf1.	SIGNOR-178034
O95243	P04626	0	phosphorylation	up-regulates activity	0.2	Importantly, we found that overexpression of HER2 alone is sufficient to induce MED1 phosphorylation at Thr (1032), a key site that is known to be critical for its functions, whereas blockage of HER2 or its downstream MAP kinase diminishes its phosphor ylation levels in these cells.	SIGNOR-279408
Q9NQU5	Q9BY11	1	phosphorylation	up-regulates activity	0.2	We identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo.	SIGNOR-263021
Q9NVI1	Q9NW38	0	ubiquitination	up-regulates activity	0.842	Phosphorylation of FANCD2 and Fanconi anemia core components (broken pink circles) affects the efficiency of, but is not essential for, ID ubiquitination by the FA core complex, together with E1 and UBE2T. Analogously, ubiquitination of FANCD2 (solid orange ovals) is essential for DNA repair, activating the ID complex for chromatin binding	SIGNOR-263266
Q96BH1	Q969F2	1	polyubiquitination	down-regulates quantity by destabilization	0.451	Here, we show that Naked2 is a short-lived protein with a half-life of 60 min caused by its rapid ubiquitin-mediated proteasomal degradation. Overexpression of TGF-alpha stabilizes Naked2 protein in an EGF receptor (EGFR)-independent manner; a physical interaction between the cytoplasmic tail of TGF-alpha and Naked2 is necessary and sufficient for this protection. We have identified a RING finger protein, AO7/RNF25, as a ubiquitin ligase for Naked2, and we have shown that overexpression of TGF-alpha reduces binding of AO7 to Naked2.	SIGNOR-271738
Q12864	P20823	0	transcriptional regulation	up-regulates quantity by expression	0.313	The present study aims to identify the transcription factors which interact and regulate CDH17 promoter activity that might contribute to the up-regulation of CDH17 gene in human HCC\|we identified hepatic nuclear factor 1α (HNF1α) and caudal-related homeobox 2 (CDX2) binding sites at the proximal promoter region which modulate the CDH17 promoter activities in two HCC cell lines (Hep3B and MHCC97L)	SIGNOR-253970
Q13464	O43293	1	phosphorylation	up-regulates activity	0.306	ROCK1 phosphorylates and activates ZIPK suggesting that at least some of these physiological functions may require both enzymes.	SIGNOR-279102
Q9ULA0	Q13107	1	cleavage	down-regulates quantity by destabilization	0.2	A further analysis showed that the hydrolysis pathway contributes to DNPEP-mediated degradation of USP4 (Supporting Information Figs. S3A–S3F). The interaction between USP4 and DNPEP was confirmed by coIP assays	SIGNOR-275652
P53779	P54259	1	phosphorylation	down-regulates activity	0.2	Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-jun nh2-terminal kinase. serine 734 of the drpla protein is a phospho-acceptor site by jnk. The phosphorylation may be coupled to the activation of a protease. The molecular size of drpla protein detected in the rat brain with the specific phosphopeptide antibody was 150_kda, which was slightly smaller than that expected from the sequence and the results with the human protein. The phosphorylated forms of ha-tagged human drpla gradually disappeared after osmotic treatment,	SIGNOR-102394
P46734	Q16584	0	phosphorylation	up-regulates activity	0.492	Immunoprecipitated mlk-3 catalyzed the phosphorylation of sek1 in vitro, and co-transfected mlk-3 induced phosphorylation of sek1 and mkk3 at sites required for activation, suggesting direct regulation of these protein kinases.	SIGNOR-45788
P20339	P53611	0	lipidation	up-regulates activity	0.491	Prenylation (or geranylgeranylation) of Rab GTPases is catalysed by RGGT (Rab geranylgeranyl transferase) and requires REP (Rab escort protein). In the classical pathway, REP associates first with unprenylated Rab, which is then prenylated by RGGT. In the alternative pathway, REP associates first with RGGT; this complex then binds and prenylates Rab proteins. Rab GTPases need to be geranylgeranylated on either one or two cysteine residues in their Ctermini in order to localize to the correct intracellular membrane and be functional	SIGNOR-265573
P23352	O00712	0	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268878
P00519	P55211	1	phosphorylation	up-regulates	0.513	C-abl phosphorylates casp9 on tyr-153 in vitro and in vivo in response to dna damage.The Present results demonstrate that c-abl binds directly to casp9.	SIGNOR-133260
P29317	P12931	0	phosphorylation	up-regulates activity	0.454	SRC phosphorylates EPHA2 on Tyr594\|. It is therefore likely that this phosphorylation site is included in the binding motif of an additional signalling molecule required for cell transformation.	SIGNOR-246104
Q86YT6	O00548	1	ubiquitination	up-regulates activity	0.743	Mib physically interacts with Delta and promotes its ubiquitination and internalization [66], which have been shown to up-regulate Notch activity.	SIGNOR-209750
P45984	Q12968	1	relocalization	down-regulates	0.711	Jnks directly phosphorylate nuclear factor of activated t-cell (nfat) transcription factors, thus antagonizing the effects of calcium-regulated signaling through the protein phosphatase calcineurin.	SIGNOR-103360
Q96EB6	Q04206	1	deacetylation	down-regulates activity	0.722	SIRT1 physically interacts with the RelA/p65 subunit of NF-kappaB and inhibits transcription by deacetylating RelA/p65 at lysine 310.	SIGNOR-238817
Q969H0	P46531	1	ubiquitination	down-regulates quantity by destabilization	0.613	Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo.	SIGNOR-130706
P04049	Q92934	1	phosphorylation	down-regulates	0.66	The activation of several major anti-apoptotic signaling pathways correlates with an increase in the phosphorylation of bad on ser-112, ser-136, and ser-155. These phosphorylation events result in bad inactivation through sequestration by 14-3-3 proteins	SIGNOR-155293
P42224	Q06124	0	dephosphorylation	down-regulates activity	0.743	SHP-2 is a dual-specificity phosphatase involved in Stat1 dephosphorylation at both tyrosine and serine residues in nuclei\|In SHP-2-/- mouse fibroblast cells, Stat1 phosphorylation at both the tyrosine residue Tyr(701) and the serine residue Ser(727) \|Overexpression of SHP-2 in 293T cells inhibited IFNgamma-dependent Stat1 phosphorylation and suppressed Stat1-dependent induction of luciferase activity.	SIGNOR-248673
O95243	P17252	0	phosphorylation	up-regulates activity	0.2	Phosphorylation of MBD4 promotes 5-meC glycosylase activity Further evidence emerged to support the involvement of MBD4 in active demethylation. Protein-kinase C phosphorylation of MBD4 at two specific serine residues (165 and 262) following parathyroid hormone stimulation was shown to promote demethylation within the CYP27B1 gene promoter [12]	SIGNOR-275672
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
O15297	P16104	1	dephosphorylation	down-regulates	0.2	Wild-type p53-induced phosphatase 1 dephosphorylates histone variant gamma-h2ax and suppresses dna double strand break repair. Here, we demonstrate that the wild-type p53-induced phosphatase 1 (wip1) also dephosphorylates gamma-h2ax at serine 139 in vitro and in vivo.	SIGNOR-163693
P29350	Q14247	1	dephosphorylation	down-regulates activity	0.2	Shp1 interacts with cortactin and reduces cortactin phosphorylation at tyrosine 421; 3.\|induction of Shp1-cortactin complex formation impairs cortactin scaffolding-activity and negatively affects invadopodia behaviour; 4.	SIGNOR-277003
P0DP24	P00533	0	phosphorylation	down-regulates	0.345	Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.	SIGNOR-266319
P12931	O15530	1	phosphorylation	up-regulates activity	0.585	Using site-directed mutants, we show that, although phosphorylation on tyr-373/376 is important for pdk1 activity, phosphorylation on tyr-9 has no effect on the activity of the kinase. Both of these residues can be phosphorylated by v-src tyrosine kinase in vitro, and co-expression of v-src leads to tyrosine phosphorylation and activation of pdk1.	SIGNOR-109533
Q99986	Q96GD4	1	phosphorylation	up-regulates activity	0.429	In the VRK1 overexpression of experiment, VRK1 caused a significant stabilization of AURKB, with no change in level after 24h, which is consistent with protection of AURKB against its known degradation by ubiquitylation .\|The phosphorylation of AURKB by VRK1 and VRK1 by AURKB was tested using a kinase-dead form as substrate.	SIGNOR-280160
Q9NZQ7	Q8NEZ4	0	transcriptional regulation	up-regulates quantity by expression	0.2	MLL3 enhances the transcription of PD-L1 and regulates anti-tumor immunity. We found that MLL3 bound to the enhancer of PD-L1.	SIGNOR-260040
O75385	P42345	0	phosphorylation	down-regulates activity	0.849	mTORC1, which is often referred to as the gatekeeper to autophagy, is a key regulator of the Ulk1-Atg13-FIP200 kinase complex.11,14,25 Under nutrient-rich conditions, active mTORC1 associates with and inactivates the Ulk1-Atg13-FIP200 complex by phosphorylating Ulk1 and Atg13.	SIGNOR-183903
P18206	P00519	0	phosphorylation	up-regulates activity	0.38	Abl is the tyrosine kinase that phosphorylates vinculin Y822.\|Finally we show that Abl inhibition prevents vinculin actions in cadherin containing complexes, resulting in defects in cell stiffening.	SIGNOR-278464
P17612	P29474	1	phosphorylation	up-regulates	0.399	Recently many investigators have shown that protein phosphorylation of enos by several serine/threonine kinases is a critical control step for no production by endothelial cells. Phosphorylation by amp kinase, akt (or protein kinase b), or protein kinase aon serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no.	SIGNOR-112371
Q9H4A3	Q9H2X9	1	phosphorylation	down-regulates activity	0.461	The activity of the neuronal specific KCC2 had recently been shown to be regulated by the WNK1 kinase, where phosphorylation decreased KCC2 activation .\|WNK1 phosphorylation of KCC2 occurs in immature neurons but is absent in adult neurons , , emphasizing a developmental role.	SIGNOR-280163
Q96GD4	O15392	1	phosphorylation	down-regulates	0.795	Phosphorylation by aurora-b negatively regulates survivin function . hat survivin is phosphorylated at t117 during mitosis, and once phosphorylated, dephosphorylation is crucial for chromosome congression and progression into anaphaseduring mitosis	SIGNOR-154569
Q8IW41	P47712	1	phosphorylation	up-regulates activity	0.334	The p38-activated protein kinases MNK1, MSK1, and PRAK1 phosphorylate cPLA2 in vitro uniquely on Ser-727. By using Chinese hamster ovary, HeLa, and HEK293 cells stably transfected with wild type and phosphorylation site mutant forms of cPLA2, we show that phosphorylation of cPLA2 at both Ser-505 and Ser-727 and elevation of Ca(2+) leads to its activation in agonist-stimulated cells.	SIGNOR-250162
Q9NXV6	Q00987	0	ubiquitination	down-regulates	0.37	Carf interacts with hdm2 and is ubiquitinated and negatively regulated by hdm2 by proteasome-dependent degradation.	SIGNOR-160974
Q05655	Q9BZK7	1	phosphorylation	up-regulates activity	0.2	In addition, we describe that the functions and the specificity of these two highly- related exchange factors is tightly regulated by signal-induced phosphorylation events at the level of target gene promoters, as exemplified by the role of TBLR1 phosphorylation at Ser 123 by PKCδ upon retinoic acid or estrogen stimulation.	SIGNOR-260903
Q01813	P31749	0	phosphorylation	up-regulates quantity	0.564	A reduction in AKT expression as a result of AKT1 shRNA expression or MK-2206 treatment decreased the half-life of endogenous PFKP, while the expression of active Myr-AKT1 prolonged the half-life of PFKP.\|In addition, depletion of endogenous PFKP and reconstitution of RNAi resistant WT Flag-rPFKP or Flag-rPFKP S386A expression in U251 or U87 and EGFRvIII cells revealed that the S386A mutation abolished PFKP phosphorylation induced by EGF, constitutively active Myr-AKT1, and EGFRvIII.	SIGNOR-279788
Q96T88	P11309	0	phosphorylation	down-regulates quantity by destabilization	0.2	Here we report that UHRF1 is a novel substrate of PIM1 kinase, which could be phosphorylated at Ser311 and therefore promoted to degradation.	SIGNOR-277349
Q12772	P01130	1	transcriptional regulation	up-regulates quantity by expression	0.772	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-254453
P05771	Q01844	1	phosphorylation	down-regulates activity	0.275	Here we report thatews, a nuclearrna-bindingprooncoprotein, contains an iq domain, is phosphorylated byproteinkinase c, and interacts with calmodulin. Interestingly, pkc phosphorylation of ews inhibits its binding to rna homopolymers, and conversely,rna binding to ews interferes with pkc phosphorylation./ these data indicate that ews contains an iq domain with ser266 acting as the primary site for pkc phosphorylation.	SIGNOR-52854
Q9UBK2	P20393	1	transcriptional regulation	up-regulates quantity by expression	0.522	Transcriptional coactivator PGC-1α integrates the mammalian clock and energy metabolism. Here we show that PGC-1alpha (Ppargc1a), a transcriptional coactivator that regulates energy metabolism, is rhythmically expressed in the liver and skeletal muscle of mice. PGC-1alpha stimulates the expression of clock genes, notably Bmal1 (Arntl) and Rev-erbalpha (Nr1d1), through coactivation of the ROR family of orphan nuclear receptors. Chromatin immunoprecipitation (ChIP) assays in HepG2 cells indicate that PGC-1α is present near RORE on the proximal Bmal1 promoter.These results indicate that PGC-1α activates Bmal1 transcription by altering the local chromatin environment from a repressive to an active state.	SIGNOR-268030
P27361	P23396	1	phosphorylation	up-regulates	0.351	Erk phosphorylates threonine 42 residue of ribosomal protein s3.	SIGNOR-137175
Q96HP0	P31749	0	phosphorylation	up-regulates activity	0.372	Akt and PP2A reciprocally regulate the guanine nucleotide exchange factor Dock6 to control axon growth of sensory neurons\|At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser(1194). \| In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, whereas reintroduction of Dock6 with a phosphomimetic S1194E mutation resulted in premature branching	SIGNOR-275666
P98170	P60484	1	ubiquitination	down-regulates quantity	0.691	Finally, we found that XIAP can directly ubiquitinate PTEN in vitro.\|Overexpression of XIAP induces polyubiquitination of PTEN and proteasome dependent decrease of PTEN protein levels.	SIGNOR-278751
Q6PJ69	P51668	0	ubiquitination	up-regulates activity	0.298	Ubiquitination assays demonstrate that TRIM65 is an ubiquitin E3 ligase for TNRC6 proteins. The combination of overexpression and knockdown studies establishes that TRIM65 relieves miRNA-driven suppression of mRNA expression through ubiquitination and subsequent degradation of TNRC6. TRIM65 regulates ubiquitination and stability of TNRC6. (A) In vitro ubiquitination of TNRC6A by TRIM65 plus E1, E2 (UBCH5A, also known as UBE2D1), ATP, and HA-Ub. GST-tagged TRIM65 and mutant TRIM65 were purified from bacteria. TRIM65 regulates ubiquitination and stability of TNRC6. (A) In vitro ubiquitination of TNRC6A by TRIM65 plus E1, E2 (UBCH5A, also known as UBE2D1), ATP, and HA-Ub. GST-tagged TRIM65 and mutant TRIM65 were purified from bacteria.	SIGNOR-272175
P68400	Q8TEA8	1	phosphorylation	up-regulates activity	0.285	Here we show that DUE-B is de-phosphorylated in M phase and phosphorylated in G1/S phase. Phosphorylated DUE-B forms homodimers, whereas de-phosphorylated DUE-B interacts with the Mcm2–7 complex and aminoacyl-tRNA synthetases. We find that CKII can prime DUE-B for Cdc7 phosphorylation. Confirming the importance of DUE-B phosphorylation in replication initiation, a C-terminal Ser/Thr to Ala mutant blocks Cdc45 and RPA loading on sperm chromatin and inhibits DNA replication. DUE-B C-terminal phosphorylation sites (serine 179, 181, 182, 194, 196, 197, 204, 205, and threonine 187) were mutated to unphosphorylatable alanine (DUE-B(S/T)-A) or phosphomimic aspartic acid (DUE-B(S/T)-D).	SIGNOR-273970
Q15173	P31749	1	dephosphorylation	down-regulates	0.661	Activation of pp2a is the intermediate step between the abeta-ceramide cascade and the subsequent inactivation of akt.	SIGNOR-252615
Q02779	P45985	1	phosphorylation	up-regulates activity	0.445	MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of c-Jun N-terminal kinase/stress-activated protein kinase.	SIGNOR-278954
P27361	Q13950	1	phosphorylation	up-regulates	0.565	In this study, we identified two phosphorylation sites in runx2 at ser301 and ser319 that are required for mapk-dependent activation of runx2 transcriptional activity and osteoblast differentiation.	SIGNOR-188347
P40763	O43293	0	phosphorylation	up-regulates activity	0.401	ZIPK phosphorylated STAT3 on serine 727 (Ser727) and enhanced STAT3 transcriptional activity.	SIGNOR-279702
P17612	P36382	1	phosphorylation	up-regulates activity	0.307	Gap junction channels formed of Cx40 are modulated by protein-kinase-A-mediated phosphorylation. Macroscopic conductance and permeability of Cx40 gap junctions is strongly increased by cAMP. two serine residues that can be phosphorylated by PKA, S120 and S345	SIGNOR-249982
P06400	O15194	0	dephosphorylation	up-regulates activity	0.298	ppRB (RB phosphorylated at Ser-807/811\|Possible Mechanisms of HYA22 Action in Tumorigenesis: Dephosphorylation of RB by Transient Expression of HYA22 Isoforms.	SIGNOR-248304
P29597	P52630	1	phosphorylation	up-regulates activity	0.789	JAK1 and TYK2 will phosphorylate and activate STAT1 and STAT2 respectively, leading to the formation of the ternary interferon-stimulated gene factor 3 (ISGF3) complex, composed of STAT1, STAT2 and interferon regulatory factor 9 (IRF9).	SIGNOR-279133
Q15759	Q8IW41	1	phosphorylation	up-regulates	0.619	Prak activity was regulated by p38alpha and p38beta both in vitro and in vivo and thr182 was shown to be the regulatory phosphorylation site.	SIGNOR-58131
Q6ZVD8	Q9Y243	1	dephosphorylation	down-regulates activity	0.683	The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.\|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells.	SIGNOR-248731
Q76N32	P51955	0	phosphorylation	down-regulates quantity by destabilization	0.251	In this study we show phosphorylation of Cep68 by Nek2 creates a potential phosphodegron that directs Cep68 destruction through the activity of SCF-beta-Trcp.\|Our above results showed that Nek2 promoted mitotic degradation of Cep68.	SIGNOR-279471
Q6VAB6	P48454	0	dephosphorylation	up-regulates activity	0.259	These findings indicate that calcineurin modulates the phosphorylation state of KSR2, but not KSR1, and identifies S198, T287, and the S310 14-3-3 binding site as the KSR2 residues targeted by calcineurin.\|the negative regulators 14-3-3	SIGNOR-248527
P35638	P18848	0	transcriptional regulation	up-regulates quantity by expression	0.816	ATF4 also induces another bZIP protein C/EBP-homologous protein (CHOP), which is responsible for triggering apoptosis in cells under prolonged ER stress. ATF4 and CHOP further induce growth arrest and DNA damage–inducible protein 34 (GADD34),a regulatory subunit of protein phosphatase 1 (PP1) that dephosphorylates eIF2α. This negative feedback mechanism enables protein synthesis to resume after resolution of ER stress.	SIGNOR-260170
P38936	O60260	0	ubiquitination	down-regulates quantity by destabilization	0.2	Next, we defined whether pJNK is involved in parkin mediated p21 degradation.\|Parkin ubiquitinates p21 in vivo and in vitro in an E3 ligase-substrate dependent manner.	SIGNOR-278640
P35398	Q14643	1	transcriptional regulation	up-regulates quantity by expression	0.242	RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.	SIGNOR-266847
P49356	O14807	1	null	up-regulates activity	0.273	Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials.	SIGNOR-242562
P07355	Q5T6F2	0	ubiquitination	down-regulates quantity	0.341	UBAP2 formed a complex with Annexin A2 and promoted the degradation of Annexin A2 protein by ubiquitination	SIGNOR-261314
Q15797	Q9HAU4	0	polyubiquitination	down-regulates quantity by destabilization	0.725	Here, we report the identification of Smurf2, a new member of the Hect family of E3 ubiquitin ligases. Smurf2 selectively interacts with receptor-regulated Smads and preferentially targets Smad1 for ubiquitination and proteasome-mediated degradation. At higher expression levels, Smurf2 also decreases the protein levels of Smad2, but not Smad3.	SIGNOR-272936
P68400	P35659	1	phosphorylation	up-regulates	0.35	Dek is phosphorylated by the protein kinase ck2 in vitro and in vivo on ser32	SIGNOR-125912
Q8N122	P54646	0	phosphorylation	down-regulates activity	0.693	These results suggest that AMPK activation can induce phosphorylation of both serine 722 and serine 792.\|Raptor phosphorylation is required for inhibition of mTORC1 by AMPK	SIGNOR-163463
P16157	O94856	0	relocalization	up-regulates quantity	0.685	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-266718
P67775	O43318	1	dephosphorylation	down-regulates	0.329	Our results demonstrate that pp6 specifically down-regulates tak1 through dephosphorylation of thr-187 in the activation loop, which is likely important for suppressing inflammatory responses via tak1 signaling pathways.	SIGNOR-150369
P07359	P78536	0	cleavage	down-regulates activity	0.284	GPIbα is shed by metalloproteases such as ADAM17, a process that releases a soluble GPIbα fragment termed glycocalicin. ADAM17 cleaves within the GPIbα-based peptide (LRGV465LK) through a mechanism that is only partially understood [42]. GPIbα shedding has been shown to be constitutive but it can be increased by activation of protein kinases C (PKC) or inhibition of calmodulin [42, 43]. Shedding leads to decreased receptor density	SIGNOR-261861

P43403

Q9UQQ2

1

phosphorylation

up-regulates

0.363

In vitro tyrosine phosphorylation of lnk by lck and zap-70. Tyrosine 297 would appear to be an attractive target for phosphorylation within the c-terminal domain. Our studies suggest that although lnk may participate in tcr signaling, its functions are in no way limiting during t cell development or activation.

SIGNOR-48854

P00742

P01008

0

cleavage

down-regulates activity

0.877

Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1

SIGNOR-264138

P07585

P08254

0

cleavage

down-regulates quantity by destabilization

0.673

Degradation of decorin by matrix metalloproteinases. These data indicate proteolytic degradation of DCN by MMP-2, MMP-3 and MMP-7, and suggest the possibility that, under pathophysiological conditions, the digestion by the MMPs may induce tissue reactions mediated by TGF-beta1 released from DCN in the connective tissues.

SIGNOR-256353

P54646

Q13085

1

phosphorylation

down-regulates

0.697

Significant negative linear correlations between phospho-acc and acc activity were observed in all models (p < 0.01). The decline in acc activity was related to the decrease in pcr and the rise in amp. A relationship between phospho-ampk (threonine 172) and activity of ampk immunoprecipitated with anti-alpha(2) subunit antibody preparation was also observed.

SIGNOR-87583

P55212

P49768

1

cleavage

up-regulates activity

0.372

Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.

SIGNOR-261753

Q6A1A2

P31749

1

phosphorylation

up-regulates

0.2

Akt to the plasma membrane where it is phosphorylated and activated by phosphoinositide-dependent kinase (pdk) 1 and pdk2.

SIGNOR-252628

Q14289

O43294

1

phosphorylation

up-regulates activity

0.71

Hic-5 is a CAKbeta-binding protein localized at focal adhesions. Here we show that overexpression of CAKbeta or Fyn, but not FAK, enhanced the tyrosine phosphorylation of coexpressed Hic-5 in COS-7 cells. The Y60F mutant of Hic-5 was not phosphorylated, and Hic-5 phosphorylated on tyrosine 60 was bound specifically to the SH2 domain of Csk. Specific phosphorylation of Hic-5 by CAKbeta and Fyn may activate a signaling pathway mediated by Hic-5.

SIGNOR-262876

O75604

P37173

0

phosphorylation

up-regulates activity

0.2

Here, we report the role of USP2a in promoting metastasis by facilitating TGF-β-triggered signaling. USP2a interacts with TGFBR1 and TGFBR2 upon TGF-β stimulation and removes K33-linked polyubiquitin chains from Lys502 of TGFBR1, promoting the recruitment of SMAD2/3. Simultaneously, TGFBR2 phosphorylates Ser207/Ser225 of USP2a, leading to the disassociation of SMAD2/3 from TGFBR1.

SIGNOR-273604

Q9H9S0

P27361

0

phosphorylation

down-regulates

0.492

We found that activation of ERK1 signaling inhibited transactivation activity of Nanog.|We showed the direct phosphorylation of Nanog by ERK1 and clearly showed that Ser52 is the major phosphorylation site and Ser65 is weakly phosphorylated by ERK1.

SIGNOR-278487

P23771

Q9UI32

1

transcriptional regulation

up-regulates quantity by expression

0.332

Thus, GATA3 contributes to the elevated expression of GLS2 in luminal-subtype breast cancers.

SIGNOR-268034

P42224

P33076

1

transcriptional regulation

up-regulates

0.539

When IFN-γ binds to its receptor, the receptor-associated protein tyrosine kinases Janus kinase I (JAK1) and JAK2 are activated (37). This leads to the phosphorylation of STAT1, which then dimerizes, translocates to the nucleus, and activates its target promoters, including the pIV promoter of Ciita

SIGNOR-256249

Q13485

Q9UNE7

0

polyubiquitination

down-regulates quantity by destabilization

0.396

We demonstrate that the coexpression of Smad1 and Smad4 with the CHIP protein results in the degradation of the Smad proteins through a ubiquitin-mediated process.

SIGNOR-272947

P49841

Q9BYG3

1

phosphorylation

up-regulates activity

0.2

The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK226-269, phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. phosphorylation of Thr234 by GSK3 proceeds only after Thr238 is already phosphorylated by CDK1.

SIGNOR-262698

P11274

P01106

0

transcriptional regulation

up-regulates quantity by expression

0.362

In the present study we demonstrate that MYC and its partner MAX bind to the BCR promoter, leading to up-regulation of BCR and BCR/ABL1 at both transcriptional and protein levels.|Here we describe a regulatory pathway modulating BCR and BCR/ABL1 expression, showing that the BCR promoter is under the transcriptional control of the MYC/MAX heterodimer.

SIGNOR-272144

O60566

O14757

0

phosphorylation

up-regulates activity

0.447

Nonetheless, in our experimental system a Chk1-dependent BubR1 phosphorylation was also observed after Noc treatment.|Possible requirement of Chk1 in U2OS cells to activate the mitotic spindle checkpoint proteins Mad2 and BubR1.

SIGNOR-280223

P09629

P68400

0

phosphorylation

down-regulates activity

0.344

Thus, we concluded that CKII can phosphorylate HOXB7 in vitro and that this phosphorylation occurs at both of the CKII target sites, S133 and T204. | Wild-type HOXB7 inhibited the differentiation of 32D cells, whereas mutations in the Pbx-binding pentapeptide motif or the DNA-binding homeodomain, as well as internal deletions of the N-terminal unique region, blocked this effect. Interestingly, mutations eliminating two target sites for casein kinase II, the glutamate-rich C terminus, or the first 14 amino acids of HOXB7, led to enhanced 32D differentiation.

SIGNOR-250896

P45983

Q5JR12

1

phosphorylation

down-regulates

0.344

Specific phosphorylation of pp2czeta at ser (92) by stress-activated jnk attenuates its phosphatase activity in cells.

SIGNOR-178930

Q96BR1

P49815

1

phosphorylation

up-regulates activity

0.434

SGK3 phosphorylates six sites on TSC2 to activate mTORC1 in an AKT-independent manner.

SIGNOR-279284

O00429

Q9BXM7

0

phosphorylation

up-regulates activity

0.6

We here demonstrate that PINK1 directly phosphorylates Drp1 on S616.

SIGNOR-279548

Q13144

P05198

1

guanine nucleotide exchange factor

up-regulates activity

0.84

EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.

SIGNOR-269123

Q9ULV8

P07949

1

ubiquitination

down-regulates quantity by destabilization

0.368

Here we show that Cbl-c binds wild-type and MEN2A isoforms of the receptor tyrosine kinase, RET, and that Cbl-c enhances ubiquitination and degradation of activated RET.|We show that Cbl-c negatively regulates RET by ubiquitinating and downregulating the activated RTK while Enigma positively regulates activated RET by preventing Cbl-c binding to RET and thus preventing RET ubiquitination and degradation while promoting RET mitogenic signaling.

SIGNOR-278674

Q14790

Q7Z434

0

relocalization

up-regulates

0.587

Another protein suggested to play a role in caspase-8 translocation to mitochondria is the mitochondrial membrane protein cardif

SIGNOR-143572

Q13705

P36896

1

phosphorylation

up-regulates activity

0.691

Activin binds directly to ActR-IIB, and this complex associates with ActR-IB, which does not bind ligand on its own. In the resulting complex, ActR-IB becomes hyperphosphorylated, and this requires the kinase activity of ActR-IIB.

SIGNOR-235146

Q9H0H5

P63000

1

gtpase-activating protein

down-regulates activity

0.586

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-260512

P17612

O00141

1

phosphorylation

up-regulates activity

0.297

In this publication, we demonstrate that cAMP can activate Sgk and that this effect is mediated by PKA, which directly phosphorylates Thr369 in Sgk.

SIGNOR-275972

Q9UHD2

O15379

1

phosphorylation

up-regulates activity

0.2

The feedback of activation of HDAC3 by TBK1 was able to further enhance IFN production and IFN-STAT activation.|We found that HDAC3 could be phosphorylated by TBK1.

SIGNOR-279662

P28482

P08235

1

phosphorylation

down-regulates quantity by destabilization

0.286

Taken together, these data suggest that ERK1/2 directly phosphorylates the MR on several serine residues present in its NTD, that the upward shift of MR is mainly due to receptor phosphorylation, and finally that these sites represent the major aldosterone-inducible targets for MR phosphorylation.MR phosphorylation limits the transcriptional activity.Taken together, these results provide evidence that MR phosphorylation plays a role in aldosterone-mediated ubiquitylation and degradation.

SIGNOR-276101

Q8TDR2

Q05D32

0

dephosphorylation

up-regulates quantity by stabilization

0.282

We found that peptides corresponding to phosphoserines 194 and 216 of PDIK1L (S385 and S413 of STK35) were efficiently dephosphorylated by SCP4, whereas no activity was detected for the other two phosphopeptides (Figure 6D).

SIGNOR-273775

P34947

P08235

1

phosphorylation

down-regulates

0.26

We report that GRK5 phosphorylates and inhibits the cardiac MR whereas GRK2 phosphorylates and desensitizes GPER.

SIGNOR-278478

P35222

P23471

0

dephosphorylation

up-regulates activity

0.378

PTPRZ1 constitutively promotes the tyrosine dephosphorylation of \u03b2-catenin, and thus \u03b2-catenin participation in TCF-mediated transcription.

SIGNOR-277044

P28482

Q13586

1

phosphorylation

up-regulates

0.351

The netrin-2-mediated nfatc3 activation was coincident with robust interactions between cdo and stim1 in myoblasts and the erk-mediated stim1 phosphorylation at serine 575

SIGNOR-192788

P52789

P04637

0

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

P68400

P54274

1

phosphorylation

up-regulates

0.2

Regulation of telomeric repeat binding factor 1 binding to telomeres by casein kinase 2-mediated phosphorylation. Mapping of the ck2 target site identified threonine 122 as a substrate in trf1. A threonine to alanine change at this position led to a diminished dna binding due to reduced dimerization of trf1.

SIGNOR-178034

O95243

P04626

0

phosphorylation

up-regulates activity

0.2

Importantly, we found that overexpression of HER2 alone is sufficient to induce MED1 phosphorylation at Thr (1032), a key site that is known to be critical for its functions, whereas blockage of HER2 or its downstream MAP kinase diminishes its phosphor ylation levels in these cells.

SIGNOR-279408

Q9NQU5

Q9BY11

1

phosphorylation

up-regulates activity

0.2

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

SIGNOR-263021

Q9NVI1

Q9NW38

0

ubiquitination

up-regulates activity

0.842

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

SIGNOR-263266

Q96BH1

Q969F2

1

polyubiquitination

down-regulates quantity by destabilization

0.451

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

SIGNOR-271738

Q12864

P20823

0

transcriptional regulation

up-regulates quantity by expression

0.313

The present study aims to identify the transcription factors which interact and regulate CDH17 promoter activity that might contribute to the up-regulation of CDH17 gene in human HCC|we identified hepatic nuclear factor 1α (HNF1α) and caudal-related homeobox 2 (CDX2) binding sites at the proximal promoter region which modulate the CDH17 promoter activities in two HCC cell lines (Hep3B and MHCC97L)

SIGNOR-253970

Q13464

O43293

1

phosphorylation

up-regulates activity

0.306

ROCK1 phosphorylates and activates ZIPK suggesting that at least some of these physiological functions may require both enzymes.

SIGNOR-279102

Q9ULA0

Q13107

1

cleavage

down-regulates quantity by destabilization

0.2

A further analysis showed that the hydrolysis pathway contributes to DNPEP-mediated degradation of USP4 (Supporting Information Figs. S3A–S3F). The interaction between USP4 and DNPEP was confirmed by coIP assays

SIGNOR-275652

P53779

P54259

1

phosphorylation

down-regulates activity

0.2

Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-jun nh2-terminal kinase. serine 734 of the drpla protein is a phospho-acceptor site by jnk. The phosphorylation may be coupled to the activation of a protease. The molecular size of drpla protein detected in the rat brain with the specific phosphopeptide antibody was 150_kda, which was slightly smaller than that expected from the sequence and the results with the human protein. The phosphorylated forms of ha-tagged human drpla gradually disappeared after osmotic treatment,

SIGNOR-102394

P46734

Q16584

0

phosphorylation

up-regulates activity

0.492

Immunoprecipitated mlk-3 catalyzed the phosphorylation of sek1 in vitro, and co-transfected mlk-3 induced phosphorylation of sek1 and mkk3 at sites required for activation, suggesting direct regulation of these protein kinases.

SIGNOR-45788

P20339

P53611

0

lipidation

up-regulates activity

0.491

Prenylation (or geranylgeranylation) of Rab GTPases is catalysed by RGGT (Rab geranylgeranyl transferase) and requires REP (Rab escort protein). In the classical pathway, REP associates first with unprenylated Rab, which is then prenylated by RGGT. In the alternative pathway, REP associates first with RGGT; this complex then binds and prenylates Rab proteins. Rab GTPases need to be geranylgeranylated on either one or two cysteine residues in their Ctermini in order to localize to the correct intracellular membrane and be functional

SIGNOR-265573

P23352

O00712

0

transcriptional regulation

down-regulates quantity

0.2

By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development

SIGNOR-268878

P00519

P55211

1

phosphorylation

up-regulates

0.513

C-abl phosphorylates casp9 on tyr-153 in vitro and in vivo in response to dna damage.The Present results demonstrate that c-abl binds directly to casp9.

SIGNOR-133260

P29317

P12931

0

phosphorylation

up-regulates activity

0.454

SRC phosphorylates EPHA2 on Tyr594|. It is therefore likely that this phosphorylation site is included in the binding motif of an additional signalling molecule required for cell transformation.

SIGNOR-246104

Q86YT6

O00548

1

ubiquitination

up-regulates activity

0.743

Mib physically interacts with Delta and promotes its ubiquitination and internalization [66], which have been shown to up-regulate Notch activity.

SIGNOR-209750

P45984

Q12968

1

relocalization

down-regulates

0.711

Jnks directly phosphorylate nuclear factor of activated t-cell (nfat) transcription factors, thus antagonizing the effects of calcium-regulated signaling through the protein phosphatase calcineurin.

SIGNOR-103360

Q96EB6

Q04206

1

deacetylation

down-regulates activity

0.722

SIRT1 physically interacts with the RelA/p65 subunit of NF-kappaB and inhibits transcription by deacetylating RelA/p65 at lysine 310.

SIGNOR-238817

Q969H0

P46531

1

ubiquitination

down-regulates quantity by destabilization

0.613

Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo.

SIGNOR-130706

P04049

Q92934

1

phosphorylation

down-regulates

0.66

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

SIGNOR-155293

P42224

Q06124

0

dephosphorylation

down-regulates activity

0.743

SHP-2 is a dual-specificity phosphatase involved in Stat1 dephosphorylation at both tyrosine and serine residues in nuclei|In SHP-2-/- mouse fibroblast cells, Stat1 phosphorylation at both the tyrosine residue Tyr(701) and the serine residue Ser(727) |Overexpression of SHP-2 in 293T cells inhibited IFNgamma-dependent Stat1 phosphorylation and suppressed Stat1-dependent induction of luciferase activity.

SIGNOR-248673

O95243

P17252

0

phosphorylation

up-regulates activity

0.2

Phosphorylation of MBD4 promotes 5-meC glycosylase activity Further evidence emerged to support the involvement of MBD4 in active demethylation. Protein-kinase C phosphorylation of MBD4 at two specific serine residues (165 and 262) following parathyroid hormone stimulation was shown to promote demethylation within the CYP27B1 gene promoter [12]

SIGNOR-275672

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

O15297

P16104

1

dephosphorylation

down-regulates

0.2

Wild-type p53-induced phosphatase 1 dephosphorylates histone variant gamma-h2ax and suppresses dna double strand break repair. Here, we demonstrate that the wild-type p53-induced phosphatase 1 (wip1) also dephosphorylates gamma-h2ax at serine 139 in vitro and in vivo.

SIGNOR-163693

P29350

Q14247

1

dephosphorylation

down-regulates activity

0.2

Shp1 interacts with cortactin and reduces cortactin phosphorylation at tyrosine 421; 3.|induction of Shp1-cortactin complex formation impairs cortactin scaffolding-activity and negatively affects invadopodia behaviour; 4.

SIGNOR-277003

P0DP24

P00533

0

phosphorylation

down-regulates

0.345

Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.

SIGNOR-266319

P12931

O15530

1

phosphorylation

up-regulates activity

0.585

Using site-directed mutants, we show that, although phosphorylation on tyr-373/376 is important for pdk1 activity, phosphorylation on tyr-9 has no effect on the activity of the kinase. Both of these residues can be phosphorylated by v-src tyrosine kinase in vitro, and co-expression of v-src leads to tyrosine phosphorylation and activation of pdk1.

SIGNOR-109533

Q99986

Q96GD4

1

phosphorylation

up-regulates activity

0.429

In the VRK1 overexpression of experiment, VRK1 caused a significant stabilization of AURKB, with no change in level after 24h, which is consistent with protection of AURKB against its known degradation by ubiquitylation .|The phosphorylation of AURKB by VRK1 and VRK1 by AURKB was tested using a kinase-dead form as substrate.

SIGNOR-280160

Q9NZQ7

Q8NEZ4

0

transcriptional regulation

up-regulates quantity by expression

0.2

MLL3 enhances the transcription of PD-L1 and regulates anti-tumor immunity. We found that MLL3 bound to the enhancer of PD-L1.

SIGNOR-260040

O75385

P42345

0

phosphorylation

down-regulates activity

0.849

mTORC1, which is often referred to as the gatekeeper to autophagy, is a key regulator of the Ulk1-Atg13-FIP200 kinase complex.11,14,25 Under nutrient-rich conditions, active mTORC1 associates with and inactivates the Ulk1-Atg13-FIP200 complex by phosphorylating Ulk1 and Atg13.

SIGNOR-183903

P18206

P00519

0

phosphorylation

up-regulates activity

0.38

Abl is the tyrosine kinase that phosphorylates vinculin Y822.|Finally we show that Abl inhibition prevents vinculin actions in cadherin containing complexes, resulting in defects in cell stiffening.

SIGNOR-278464

P17612

P29474

1

phosphorylation

up-regulates

0.399

Recently many investigators have shown that protein phosphorylation of enos by several serine/threonine kinases is a critical control step for no production by endothelial cells. Phosphorylation by amp kinase, akt (or protein kinase b), or protein kinase aon serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no.

SIGNOR-112371

Q9H4A3

Q9H2X9

1

phosphorylation

down-regulates activity

0.461

The activity of the neuronal specific KCC2 had recently been shown to be regulated by the WNK1 kinase, where phosphorylation decreased KCC2 activation .|WNK1 phosphorylation of KCC2 occurs in immature neurons but is absent in adult neurons , , emphasizing a developmental role.

SIGNOR-280163

Q96GD4

O15392

1

phosphorylation

down-regulates

0.795

Phosphorylation by aurora-b negatively regulates survivin function . hat survivin is phosphorylated at t117 during mitosis, and once phosphorylated, dephosphorylation is crucial for chromosome congression and progression into anaphaseduring mitosis

SIGNOR-154569

Q8IW41

P47712

1

phosphorylation

up-regulates activity

0.334

The p38-activated protein kinases MNK1, MSK1, and PRAK1 phosphorylate cPLA2 in vitro uniquely on Ser-727. By using Chinese hamster ovary, HeLa, and HEK293 cells stably transfected with wild type and phosphorylation site mutant forms of cPLA2, we show that phosphorylation of cPLA2 at both Ser-505 and Ser-727 and elevation of Ca(2+) leads to its activation in agonist-stimulated cells.

SIGNOR-250162

Q9NXV6

Q00987

0

ubiquitination

down-regulates

0.37

Carf interacts with hdm2 and is ubiquitinated and negatively regulated by hdm2 by proteasome-dependent degradation.

SIGNOR-160974

Q05655

Q9BZK7

1

phosphorylation

up-regulates activity

0.2

In addition, we describe that the functions and the specificity of these two highly- related exchange factors is tightly regulated by signal-induced phosphorylation events at the level of target gene promoters, as exemplified by the role of TBLR1 phosphorylation at Ser 123 by PKCδ upon retinoic acid or estrogen stimulation.

SIGNOR-260903

Q01813

P31749

0

phosphorylation

up-regulates quantity

0.564

A reduction in AKT expression as a result of AKT1 shRNA expression or MK-2206 treatment decreased the half-life of endogenous PFKP, while the expression of active Myr-AKT1 prolonged the half-life of PFKP.|In addition, depletion of endogenous PFKP and reconstitution of RNAi resistant WT Flag-rPFKP or Flag-rPFKP S386A expression in U251 or U87 and EGFRvIII cells revealed that the S386A mutation abolished PFKP phosphorylation induced by EGF, constitutively active Myr-AKT1, and EGFRvIII.

SIGNOR-279788

Q96T88

P11309

0

phosphorylation

down-regulates quantity by destabilization

0.2

Here we report that UHRF1 is a novel substrate of PIM1 kinase, which could be phosphorylated at Ser311 and therefore promoted to degradation.

SIGNOR-277349

Q12772

P01130

1

transcriptional regulation

up-regulates quantity by expression

0.772

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-254453

P05771

Q01844

1

phosphorylation

down-regulates activity

0.275

Here we report thatews, a nuclearrna-bindingprooncoprotein, contains an iq domain, is phosphorylated byproteinkinase c, and interacts with calmodulin. Interestingly, pkc phosphorylation of ews inhibits its binding to rna homopolymers, and conversely,rna binding to ews interferes with pkc phosphorylation./ these data indicate that ews contains an iq domain with ser266 acting as the primary site for pkc phosphorylation.

SIGNOR-52854

Q9UBK2

P20393

1

transcriptional regulation

up-regulates quantity by expression

0.522

Transcriptional coactivator PGC-1α integrates the mammalian clock and energy metabolism. Here we show that PGC-1alpha (Ppargc1a), a transcriptional coactivator that regulates energy metabolism, is rhythmically expressed in the liver and skeletal muscle of mice. PGC-1alpha stimulates the expression of clock genes, notably Bmal1 (Arntl) and Rev-erbalpha (Nr1d1), through coactivation of the ROR family of orphan nuclear receptors. Chromatin immunoprecipitation (ChIP) assays in HepG2 cells indicate that PGC-1α is present near RORE on the proximal Bmal1 promoter.These results indicate that PGC-1α activates Bmal1 transcription by altering the local chromatin environment from a repressive to an active state.

SIGNOR-268030

P27361

P23396

1

phosphorylation

up-regulates

0.351

Erk phosphorylates threonine 42 residue of ribosomal protein s3.

SIGNOR-137175

Q96HP0

P31749

0

phosphorylation

up-regulates activity

0.372

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

SIGNOR-275666

P98170

P60484

1

ubiquitination

down-regulates quantity

0.691

Finally, we found that XIAP can directly ubiquitinate PTEN in vitro.|Overexpression of XIAP induces polyubiquitination of PTEN and proteasome dependent decrease of PTEN protein levels.

SIGNOR-278751

Q6PJ69

P51668

0

ubiquitination

up-regulates activity

0.298

Ubiquitination assays demonstrate that TRIM65 is an ubiquitin E3 ligase for TNRC6 proteins. The combination of overexpression and knockdown studies establishes that TRIM65 relieves miRNA-driven suppression of mRNA expression through ubiquitination and subsequent degradation of TNRC6. TRIM65 regulates ubiquitination and stability of TNRC6. (A) In vitro ubiquitination of TNRC6A by TRIM65 plus E1, E2 (UBCH5A, also known as UBE2D1), ATP, and HA-Ub. GST-tagged TRIM65 and mutant TRIM65 were purified from bacteria. TRIM65 regulates ubiquitination and stability of TNRC6. (A) In vitro ubiquitination of TNRC6A by TRIM65 plus E1, E2 (UBCH5A, also known as UBE2D1), ATP, and HA-Ub. GST-tagged TRIM65 and mutant TRIM65 were purified from bacteria.

SIGNOR-272175

P68400

Q8TEA8

1

phosphorylation

up-regulates activity

0.285

Here we show that DUE-B is de-phosphorylated in M phase and phosphorylated in G1/S phase. Phosphorylated DUE-B forms homodimers, whereas de-phosphorylated DUE-B interacts with the Mcm2–7 complex and aminoacyl-tRNA synthetases. We find that CKII can prime DUE-B for Cdc7 phosphorylation. Confirming the importance of DUE-B phosphorylation in replication initiation, a C-terminal Ser/Thr to Ala mutant blocks Cdc45 and RPA loading on sperm chromatin and inhibits DNA replication. DUE-B C-terminal phosphorylation sites (serine 179, 181, 182, 194, 196, 197, 204, 205, and threonine 187) were mutated to unphosphorylatable alanine (DUE-B(S/T)-A) or phosphomimic aspartic acid (DUE-B(S/T)-D).

SIGNOR-273970

Q15173

P31749

1

dephosphorylation

down-regulates

0.661

Activation of pp2a is the intermediate step between the abeta-ceramide cascade and the subsequent inactivation of akt.

SIGNOR-252615

Q02779

P45985

1

phosphorylation

up-regulates activity

0.445

MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of c-Jun N-terminal kinase/stress-activated protein kinase.

SIGNOR-278954

P27361

Q13950

1

phosphorylation

up-regulates

0.565

In this study, we identified two phosphorylation sites in runx2 at ser301 and ser319 that are required for mapk-dependent activation of runx2 transcriptional activity and osteoblast differentiation.

SIGNOR-188347

P40763

O43293

0

phosphorylation

up-regulates activity

0.401

ZIPK phosphorylated STAT3 on serine 727 (Ser727) and enhanced STAT3 transcriptional activity.

SIGNOR-279702

P17612

P36382

1

phosphorylation

up-regulates activity

0.307

Gap junction channels formed of Cx40 are modulated by protein-kinase-A-mediated phosphorylation. Macroscopic conductance and permeability of Cx40 gap junctions is strongly increased by cAMP. two serine residues that can be phosphorylated by PKA, S120 and S345

SIGNOR-249982

P06400

O15194

0

dephosphorylation

up-regulates activity

0.298

ppRB (RB phosphorylated at Ser-807/811|Possible Mechanisms of HYA22 Action in Tumorigenesis: Dephosphorylation of RB by Transient Expression of HYA22 Isoforms.

SIGNOR-248304

P29597

P52630

1

phosphorylation

up-regulates activity

0.789

JAK1 and TYK2 will phosphorylate and activate STAT1 and STAT2 respectively, leading to the formation of the ternary interferon-stimulated gene factor 3 (ISGF3) complex, composed of STAT1, STAT2 and interferon regulatory factor 9 (IRF9).

SIGNOR-279133

Q15759

Q8IW41

1

phosphorylation

up-regulates

0.619

Prak activity was regulated by p38alpha and p38beta both in vitro and in vivo and thr182 was shown to be the regulatory phosphorylation site.

SIGNOR-58131

Q6ZVD8

Q9Y243

1

dephosphorylation

down-regulates activity

0.683

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

SIGNOR-248731

Q76N32

P51955

0

phosphorylation

down-regulates quantity by destabilization

0.251

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

SIGNOR-279471

Q6VAB6

P48454

0

dephosphorylation

up-regulates activity

0.259

These findings indicate that calcineurin modulates the phosphorylation state of KSR2, but not KSR1, and identifies S198, T287, and the S310 14-3-3 binding site as the KSR2 residues targeted by calcineurin.|the negative regulators 14-3-3

SIGNOR-248527

P35638

P18848

0

transcriptional regulation

up-regulates quantity by expression

0.816

ATF4 also induces another bZIP protein C/EBP-homologous protein (CHOP), which is responsible for triggering apoptosis in cells under prolonged ER stress. ATF4 and CHOP further induce growth arrest and DNA damage–inducible protein 34 (GADD34),a regulatory subunit of protein phosphatase 1 (PP1) that dephosphorylates eIF2α. This negative feedback mechanism enables protein synthesis to resume after resolution of ER stress.

SIGNOR-260170

P38936

O60260

0

ubiquitination

down-regulates quantity by destabilization

0.2

Next, we defined whether pJNK is involved in parkin mediated p21 degradation.|Parkin ubiquitinates p21 in vivo and in vitro in an E3 ligase-substrate dependent manner.

SIGNOR-278640

P35398

Q14643

1

transcriptional regulation

up-regulates quantity by expression

0.242

RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.

SIGNOR-266847

P49356

O14807

1

null

up-regulates activity

0.273

Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials.

SIGNOR-242562

P07355

Q5T6F2

0

ubiquitination

down-regulates quantity

0.341

UBAP2 formed a complex with Annexin A2 and promoted the degradation of Annexin A2 protein by ubiquitination

SIGNOR-261314

Q15797

Q9HAU4

0

polyubiquitination

down-regulates quantity by destabilization

0.725

Here, we report the identification of Smurf2, a new member of the Hect family of E3 ubiquitin ligases. Smurf2 selectively interacts with receptor-regulated Smads and preferentially targets Smad1 for ubiquitination and proteasome-mediated degradation. At higher expression levels, Smurf2 also decreases the protein levels of Smad2, but not Smad3.

SIGNOR-272936

P68400

P35659

1

phosphorylation

up-regulates

0.35

Dek is phosphorylated by the protein kinase ck2 in vitro and in vivo on ser32

SIGNOR-125912

Q8N122

P54646

0

phosphorylation

down-regulates activity

0.693

These results suggest that AMPK activation can induce phosphorylation of both serine 722 and serine 792.|Raptor phosphorylation is required for inhibition of mTORC1 by AMPK

SIGNOR-163463

P16157

O94856

0

relocalization

up-regulates quantity

0.685

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-266718

P67775

O43318

1

dephosphorylation

down-regulates

0.329

Our results demonstrate that pp6 specifically down-regulates tak1 through dephosphorylation of thr-187 in the activation loop, which is likely important for suppressing inflammatory responses via tak1 signaling pathways.

SIGNOR-150369

P07359

P78536

0

cleavage

down-regulates activity

0.284

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

SIGNOR-261861