GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P16949	P28482	0	phosphorylation	down-regulates	0.452	Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. The kinases involved in phosphorylating stmn ser-16 and ser-63 include camp-dependent protein kinase (pka) and pak1, whereas stmn ser-25 and ser-38 have been shown to be targets for proline-directed serine/threonine kinases such as cyclin-dependent kinases, erk1/2, and members of the p38 mapk subfamily.	SIGNOR-166686
O43318	Q15653	1	phosphorylation	down-regulates	0.515	Overexpression oftak1together with its activator protein,tak1binding protein 1 (tab1), induced thenucleartranslocation of nf-kappa b p50/p65 heterodimer accompanied by the degradation of i kappa b alpha and i kappa b beta, and the expression of kappa b-dependent reporter gene.	SIGNOR-55719
P67809	P78527	0	phosphorylation	up-regulates activity	0.338	The DNA-PK subunits and YB-1 phosphorylated at T89 were found colocalized suggesting their in vivo interaction.DNA-PK directly phosphorylates YB-1 and, this way, modulates YB-1 function. Point mutation of YB-1 at this residue abrogated the translocation of YB-1 into the nucleus.	SIGNOR-277611
P31943	P12931	1	post transcriptional regulation	up-regulates quantity by expression	0.291	HnRNP H is a component of a splicing enhancer complex that activates a c-src alternative exon in neuronal cells.	SIGNOR-261273
P28482	Q9BQQ3	1	phosphorylation	down-regulates activity	0.27	Here we show that GRASP65 is phosphorylated on serine 277 in interphase cells, and this is strongly enhanced in response to the addition of serum or epidermal growth factor. This is directly mediated by ERK suggesting that GRASP65 has some role in growth factor signal transduction. These results argue against Ser-277 phosphorylation alone causing the dissolution of GRASP65 oligomers and cisternal unstacking, although it may make a significant contribution to these events.	SIGNOR-262841
Q03112	Q00526	0	phosphorylation	up-regulates activity	0.2	The motif harbouring S436 is a target of CDK2 and CDK3 kinases, which interacted with EVI1-WT. The methyltransferase DNMT3A bound preferentially to EVI1-WT compared with EVI1-S436A, and a hypomethylated cell population associated by EVI1-WT expression in murine haematopoietic progenitors is not maintained with EVI1-S436A.	SIGNOR-273431
P06241	Q05655	1	phosphorylation	up-regulates activity	0.597	In conclusion, our in vitro data and previous report ( xref ) demonstrate that Fyn phosphorylation of Y311 on PKC\u03b4 activates the apoptotic signaling cascade in DAergic neurons in response to neurotoxic insults.	SIGNOR-279737
O15350	O15111	0	phosphorylation	up-regulates activity	0.336	IKK-alpha had an ability to stabilize p73 by inhibiting its polyubiquitination, and enhanced p73 mediated transcriptional activation as well as proapoptotic activity.\|In addition, IKK-alpha phosphorylated the NH 2 -terminal portion of p73 and a kinase deficient mutant form of IKK-alpha had undetectable effect on p73.	SIGNOR-279697
Q96QF0	Q15208	0	phosphorylation	up-regulates activity	0.366	We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation.	SIGNOR-263036
P19174	P17612	0	phosphorylation	down-regulates	0.2	The observation that pka also phosphorylates plc-yl on serine 1248 suggests that phosphorylation of this residue may be a common mechanism by which pkc and pka inhibit plc-yl.	SIGNOR-17901
P10636-2	P17252	0	phosphorylation	down-regulates activity	0.265	We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.	SIGNOR-275441
P07196	P17612	0	phosphorylation	down-regulates activity	0.2	Phosphorylation of neurofilament-L protein (NF-L) by the catalytic subunit of cAMP-dependent protein kinase (A-kinase) inhibits the reassembly of NF-L and disassembles filamentous NF-L.	SIGNOR-252401
P07225	P38435	0	carboxylation	up-regulates activity	0.613	Gamma-carboxylation is essential in the activation and proper functioning of multiple VK-dependent proteins (VKDP), the most well-known of which are involved in blood clotting, including coagulation factors (FII, FVII, FIX and FX) and natural anti-clotting agents (protein C, protein S (ProS; OMIM*176880) and protein Z	SIGNOR-265924
P17676	P35247	1	transcriptional regulation	up-regulates quantity by expression	0.251	Cotransfection of C/EBPalpha, C/EBPbeta, or C/EBPdelta cDNA in H441 lung adenocarcinoma cells significantly increased the luciferase activity of a wild-type SP-D promoter construct containing 698 bp of upstream sequence (SS698). Transfection of C/EBP also increased the level of endogenous SP-D mRNA in H441 cells\| Thus, interactions among C/EBP elements in the near-distal promoter can modulate the promoter activity of SP-D.	SIGNOR-254045
Q16827	P07948	1	dephosphorylation	down-regulates activity	0.325	Both Lyn and ZAP70 were dephosphorylated by wild-type PTPROt, but not by its catalytic site mutant.\|Lyn kinase and ZAP70 are substrates of PTPROt in B-cells: Lyn inactivation by PTPROt sensitizes leukemia cells to VEGF-R inhibitor pazopanib.	SIGNOR-277144
P68400	P08047	1	phosphorylation	down-regulates activity	0.34	Casein kinase II-mediated phosphorylation of the C terminus of Sp1 decreases its DNA binding activity. \| Mutation of a consensus CKII site at amino acid 579, within the second zinc finger, eliminates phosphorylation of this site and the CKII-mediated inhibition of Sp1 binding.	SIGNOR-250954
O75365	P05787	1	dephosphorylation	down-regulates activity	0.272	the cytoskeletal intermediate filament keratin 8 (KRT8) was identified as a physiological PRL-3-interacting protein. Indeed, treatment with the PRL-3 inhibitor effectively suppressed the phosphorylation of KRT8 at S73 and S431	SIGNOR-248341
P40763	P01189	1	transcriptional regulation	up-regulates quantity by expression	0.638	We show that phospho-STAT3 activates POMC promoter in response to leptin signaling through a mechanism that requires an SP1-binding site in the POMC promoter.	SIGNOR-263497
Q9P0L2	P11137	1	phosphorylation	down-regulates activity	0.418	Here we show that p110mark phosphorylates analogous KXGS sites in the microtubule binding domains of the neuronal MAP2 and the ubiquitous MAP4. Phosphorylation in vitro leads to the dissociation of MAP2 and MAP4 from microtubules and to a pronounced increase in dynamic instability.	SIGNOR-250166
P29353	P17706	0	dephosphorylation	down-regulates activity	0.572	However, TC45 inhibited the EGF-induced association of p52Shc with Grb2, which was attributed to the ability of the PTP to recognize specifically p52Shc phosphorylated on Y239. These results indicate that TC45 recognizes not only selected substrates in a cellular context but also specific sites within substrates and thus may regulate discrete signaling events.	SIGNOR-248397
P0C5Z0	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265407
P35222	P51955	0	phosphorylation	down-regulates quantity	0.469	NEK2 silencing reduced the phosphorylation of beta-catenin at Ser33 and Ser37, but did not decrease the level of total beta-catenin.\|NEK2 slightly decreased the level of total beta-catenin (XREF_FIG).	SIGNOR-278173
Q96GF1	O14641	1	polyubiquitination	down-regulates quantity by destabilization	0.466	The E3 ligase RNF185 negatively regulates osteogenic differentiation by targeting Dvl2 for degradation. Overexpression of RNF185 decreases the exogenous and endogenous level of Dvl2, promotes the ubiquitination and degradation of Dvl2	SIGNOR-272173
P68431	Q9UQB9	0	phosphorylation	up-regulates activity	0.2	Phosphorylation at ser-11 (h3s10ph) by aurkb is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. Phosphorylation at ser-11 (h3s10ph) by aurkb is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis.	SIGNOR-118898
Q12959	Q9UQM7	0	phosphorylation	down-regulates activity	0.649	Synapse-associated protein 97 (SAP97), a member of membrane-associated guanylate kinase protein family, has been implicated in the processes of targeting ionotropic glutamate receptors at postsynaptic sites. \| We show here that SAP97 is directly associated with NR2A through its PDZ1 domain, and CaMKII-dependent phosphorylation of SAP97-Ser-232 disrupts NR2A interaction both in an in vitro pull-out assay and in transfected COS-7 cells. Moreover, expression of SAP97(S232D) mutant has effects similar to those observed upon constitutively activating CaMKII.	SIGNOR-250618
O14757	Q06609	1	phosphorylation	up-regulates	0.843	We demonstrate that chk1 interacts with rad51, and that rad51 is phosphorylated on thr 309 in a chk1-dependent manner	SIGNOR-133375
P35637	P57678	1	relocalization	up-regulates activity	0.2	Here, we report that FUS associates with the SMN complex, mediated by U1 snRNP and by direct interactions between FUS and SMN.\|The FUS IP and pulldown revealed that FUS also associates with components of the SMN complex, including SMN and Gemins 4 and 6 \|Remarkably, the number of SMN-stained nuclear bodies was dramatically reduced in the FUS knockdown cells	SIGNOR-262105
P11802	P30304	0	dephosphorylation	up-regulates activity	0.705	Invalidation of CDK4 has no impact by itself on the cell proliferation, but invalidation of CDC25A prevents the dephosphorylation of CDK6 (Y24) and CDK4 (Y17) residues, and impedes their association with CCNDs.	SIGNOR-267568
P52564	Q14765	1	phosphorylation	up-regulates activity	0.342	MKK6, phosphorylate STAT4 on serine 721. IL-12 induces STAT4 phosphorylation on serine 721 and that mutation of serine 721 interferes with STAT4 transcriptional activity.	SIGNOR-251425
O75534	P01100	1	post transcriptional regulation	down-regulates quantity	0.295	By testing different classes of mammalian poly(A) nucleases, we identified CCR4 as a poly(A) nuclease involved in the mCRD-mediated rapid deadenylation in viv	SIGNOR-261145
P11309	P31269	0	transcriptional regulation	up-regulates quantity by expression	0.2	Thus Pim1 appears to be a direct transcriptional target of HOXA9 and a mediator of its antiapoptotic and proproliferative effects in early cells.	SIGNOR-261632
Q6AZZ1	Q92734	1	ubiquitination	down-regulates quantity by destabilization	0.451	Our results suggest that TRIM68 degrades TFG at a point of pathway convergence in which downstream events lead to the activation of both NF-kappaB and IRF3.\|TRIM68 polyubiquitinates TFG leading to its degradation via its RING domain which also plays an important role in TRIM68 negative inhibition on IFN-beta production.	SIGNOR-278737
P17252	P41594	1	phosphorylation	up-regulates activity	0.416	Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.	SIGNOR-249278
Q5VT25	Q9BZL4	1	phosphorylation	down-regulates activity	0.558	Identification of the Phosphorylation Site of p85 on Threonine 560 by MRCKα-CAT \| Wild-type p85 but not the mutant p85AA, when phosphorylated in vitro with MRCKα-CAT, showed significant reduction in the rate of MLC2 dephosphorylation. These results confirm a similar observation with MBS130 where phosphorylation of a conserved threonine 695 within a highly conserved motif was essential for the inhibition of phosphatase catalytic activity	SIGNOR-250724
P05204	P51812	0	phosphorylation	down-regulates activity	0.29	We report here that the NBD of the HMGN1 and -N2 protein family is highly and specifically phosphorylated during mitosis and that this phosphorylation has a major functional consequence: it abolishes the interaction of the proteins with its chromatin targets.	SIGNOR-249102
P11142	O75061	0	relocalization	up-regulates activity	0.883	Hsc70, recruited by the J-domain protein auxilin, mediates clathrin uncoating and release of a free vesicle, primed to fuse with a target membrane.	SIGNOR-260719
P37231	Q9UBK2	1	transcriptional regulation	up-regulates quantity by expression	0.903	NFIA binds to and activates the brown-fat-specific enhancers even before differentiation and later facilitates the binding of PPARgamma\|NFIA has at least three functions on the transcriptional regulation of brown fat [2]. First, NFIA activates adipogenesis per se, through activating the transcription of Pparg, which encodes PPARgamma. Second, NFIA also activates the brown-fat-specific gene expression (such as Ucp1 and Ppargc1a) independent of the degree of adipocyte differentiation, through facilitating the binding of PPARgamma to the brown-fat-specific enhancers. Third, NFIA represses myogenesis through suppression of myogenic transcription factors such as Myod1 as well as Myog,	SIGNOR-263984
Q13490	Q13546	1	polyubiquitination	up-regulates activity	0.768	CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.	SIGNOR-272710
A1A4S6	P61586	1	gtpase-activating protein	down-regulates activity	0.668	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-260465
Q09013	P26678	1	phosphorylation	up-regulates	0.54	Coimmunoprecipitation studies showed that dmpk and pln can physically associate. Furthermore, purified wild-type dmpk, but not a kinase-deficient mutant (k110a dmpk), phosphorylates pln in vitro	SIGNOR-131371
P06493	Q9Y6I3	1	phosphorylation	down-regulates activity	0.323	Phosphorylation of POB1 and Epsin by p34cdc2 kinase. Their phosphorylation sites (Ser411 of POB1 and Ser357 of Epsin) were determined. Phosphorylated Epsin and EpsinS357D formed a complex with α-adaptin less efficiently than wild type Epsin.	SIGNOR-262723
P28482	Q9Y463	1	phosphorylation	up-regulates activity	0.369	S421 resides within a Ser-Pro phosphoacceptor motif that is typical for ERK1/2 and recombinant ERK2 phosphorylated DYRK1B at S421 in vitro.	SIGNOR-276937
P00533	O60674	0	phosphorylation	up-regulates activity	0.612	Tyrosine at residue 1,068 of the EGFR is proposed to be one of the principal phosphorylation sites and Grb2-binding sites stimulated by growth hormone via Jak2. Our results indicate that the role of EGFR in signalling by growth hormone is to be phosphorylated by Jak2, thereby providing docking sites for Grb2 and activating MAP kinases and gene expression, independently of the intrinsic tyrosine kinase activity of EGFR.¬†	SIGNOR-251347
P45983	P45985	0	phosphorylation	up-regulates activity	0.752	Stress-activated protein kinase 1 (SAPK1), also called c-Jun N-terminal kinase (JNK), becomes activated in vivo in response to pro-inflammatory cytokines or cellular stresses. Its full activation requires the phosphorylation of a threonine and a tyrosine residue in a Thr-Pro-Tyr motif, which can be catalysed by the protein kinases mitogen-activated protein kinase kinase (MKK)4 and MKK7. Here we report that MKK4 shows a striking preference for the tyrosine residue (Tyr-185), and MKK7 a striking preference for the threonine residue (Thr-183) in three SAPK1/JNK1 isoforms tested (JNK1 alpha 1, JNK2 alpha 2 and JNK3 alpha 1).	SIGNOR-251419
O15355	P84103	1	dephosphorylation	down-regulates activity	0.2	Here, we found that the PPM1G regulated SRSF3, and high levels of PPM1G decreased SRSF3 activity in HCC cells.\|PPM1G interacted with SRSF3 and dephosphorylated SRSF3.	SIGNOR-277048
O75496	O43791	0	ubiquitination	down-regulates activity	0.2	SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. This poly-ubiquitination of Geminin prevents DNA replication over-firing by indirectly blocking the association of Cdt1 with the MCM protein complex, an interaction required for DNA unwinding and replication.	SIGNOR-268926
P55212	O60285	0	phosphorylation	down-regulates activity	0.483	ARK5 negatively regulates procaspase-6 by phosphorylation at Ser257, leading to resistance to the FasL/Fas system.	SIGNOR-250209
Q9ULK5	Q01974	0	phosphorylation	down-regulates activity	0.59	In support of this, ror2 mutants abolish Vangl2 activity gradient and localization, and ror2; vangl2 double mutants phenocopy the wnt5a limb phenotype (Gao et al., 2011).4.6.\|This process is mediated by its receptor Ror2, which in turn phosphorylates Vangl2 and induces asymmetric localization of Vangl2, propagating an activity gradient of Vangl2 in the proximal direction (Gao et al., 2011).	SIGNOR-280111
P49137	P27361	0	phosphorylation	up-regulates	0.475	Erk phosphorylates multiple cytoplasmatic and cytoskeletal proteins, including mapk-activated protein kinases and the ribosomal p70-s6 kinase	SIGNOR-201687
P17405	Q05655	0	phosphorylation	up-regulates	0.256	Activation of acid sphingomyelinase by protein kinase cdelta-mediated phosphorylation. Phosphorylation of ser(508) proved to be an indispensable step for asmase activation and membrane translocation in response to pma	SIGNOR-153276
P04637	O43474	0	transcriptional regulation	down-regulates quantity by repression	0.56	Previous work has shown that the Kruppel-like factor 4 (KLF4) transcription factor represses p53 transcription by binding to the PE21 element.	SIGNOR-270544
P48426	Q15139	0	phosphorylation	down-regulates	0.2	We conclude that the type ii pip kinases are physiological targets for pkd phosphorylation, and that this modification is likely to regulate inositol lipid turnover by inhibition of these lipid kinases.	SIGNOR-145370
Q02548	P28482	0	phosphorylation	down-regulates activity	0.351	In this study, we demonstrated that PAX5 was phosphorylated by ERK1/2 in vitro and in vivo at serines 189 and 283. This phosphorylation attenuated the transcriptional repression of BLIMP1 by PAX5.	SIGNOR-269087
Q9BXF3	Q9UJQ4	0	transcriptional regulation	up-regulates quantity by expression	0.2	SALL4 activates Cecr2 by directly binging to its promotor region and CECR2 in turn promotes reprogramming through forming a SMARCA1-contained chromatin remodeling complex with its DTT domain.	SIGNOR-263893
O75925	P17844	1	sumoylation	up-regulates	0.546	We demonstrate that the sumo e3 ligase pias1 interacts with p68 and enhances its sumo modification in vivo / sumo modification enhances p68 transcriptional repression activity and inhibits the ability of p68 to function as a coactivator of p53.	SIGNOR-153719
O75116	P05067	1	phosphorylation	up-regulates quantity	0.386	Moreover, SR3677 blocked ROCK2 phosphorylation of APP at threonine 654 (T654); in neurons, T654 was critical for APP processing to Abeta.\|These observations suggest that ROCK2 inhibition reduces Abeta levels through independent mechanisms.	SIGNOR-280109
Q13469	P49841	0	phosphorylation	down-regulates	0.561	Gsk3 was previously shown to directly phosphorylate the n-terminal regulatory domain of nfatc1, thus antagonizing the action of calcineurin and inhibiting nuclear shuttling of nfat.	SIGNOR-179784
Q9Y4K3	P04637	1	ubiquitination	up-regulates activity	0.61	Here, we show that TRAF6 E3 ligase is a crucial factor to restrict mitochondrial translocation of p53 and spontaneous apoptosis by promoting K63-linked ubiquitination of p53 at K24 in cytosol, and such ubiquitination limits the interaction between p53 and MCL-1/BAK.\|We mutated every conserved lysine (K) residue on p53 and found that TRAF6 preferentially ubiquitinates p53 at K24 in the in vivo ubiquitination assay (XREF_FIG, XREF_SUPPLEMENTARY, XREF_SUPPLEMENTARY and XREF_SUPPLEMENTARY).	SIGNOR-278728
P01024	P17676	0	transcriptional regulation	up-regulates quantity by expression	0.259	CCAAT/enhancer binding protein β directly regulates the expression of the complement component 3 gene in neural cells: implications for the pro-inflammatory effects of this transcription factor	SIGNOR-261927
Q3MIX3	P48436	1	phosphorylation	up-regulates activity	0.2	Here we investigated the mechanism of ADCK5 involved in regulating invasion and migration of lung cancer cells, and showed that ADCK5 might regulate the expression of tumor oncogene human pituitary tumor transforming gene-1 (PTTG1) by phosphorylating transcription factor SOX9\|Mutagenesis of potential serine phosphorylation sites on SOX9 indicated that serine 181 might be required to maintain transcription activation of SOX9 as well as increase PTTG1 levels.	SIGNOR-264567
Q13153	P17600	1	phosphorylation	up-regulates activity	0.349	Synapsin I is phosphorylated at Ser603 by p21-activated kinases. the Ser603 residue must be one of the pivotal sites for the release	SIGNOR-250235
O95816	P49137	0	phosphorylation	up-regulates	0.366	We provided definite evidence that mapkapk2 phosphorylates bag2 at ser 20 in vitro and in vivo. These results demonstrate that bag2 is a novel component of the p38 mapk signaling pathways.	SIGNOR-126953
P60953	P12931	0	phosphorylation	up-regulates	0.695	Epidermal growth factor-dependent regulation of cdc42 is mediated by the src tyrosine kinaseegf signaling through src appears to have dual regulatory effects on cdc42: 1). it leads to the activation of cdc42 as mediated by the vav2 guanine nucleotide exchange factor, and 2). it results in the phosphorylation of cdc42, which stimulates the binding of rhogdi, perhaps to direct the movement of cdc42 to a specific cellular site to trigger a signaling response, because cdc42-rhogdi interactions are essential for cdc42-induced cellular transformation.	SIGNOR-118206
P16885	P08631	0	phosphorylation	up-regulates activity	0.552	The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors.	SIGNOR-249364
Q05513	P28329	1	phosphorylation	up-regulates	0.288	Finally, basal chat phosphorylation in neurons is mediated predominantly by pkc at ser-476, with pkc activation increasing phosphorylation at ser-440 and enhancing chat activity.	SIGNOR-129340
O75385	P14373	0	ubiquitination	down-regulates quantity	0.2	STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination	SIGNOR-270349
Q13043	P22455	0	phosphorylation	down-regulates activity	0.2	FGFR4 phosphorylates MST1 to confer breast cancer cells resistance to MST1/2 dependent apoptosis.\|We provide evidence suggesting that by Y433-MST1 phosphorylation , FGFR4 inhibits MST1 / 2 activation .	SIGNOR-279714
P29466	P49810	1	cleavage	up-regulates activity	0.32	In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329.	SIGNOR-261748
P43354	P28482	0	phosphorylation	up-regulates	0.395	We have shown that erk2 is a kinase to phosphorylate nurr1 on multiple sites. S126 and t132, which are located near af1 core of nurr1, are dominant sites phosphorylated by erk2. reporter gene assays show that nurr1delta124-133/t185a, an erk2 phospho-site mutant form, could not further increase its transcriptional activity on th promoter, suggesting that nurr1 phosphorylation by erk2 may regulate its transcriptional activity on th promoter.	SIGNOR-157167
P36507	P55211	1	phosphorylation	down-regulates activity	0.347	Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK\|The opposing protein kinase activity is overcome by treatment with the broad-specificity kinase inhibitor staurosporine or with inhibitors of MEK1/2	SIGNOR-249386
Q9BYW2	P68363	1	methylation	up-regulates activity	0.244	The histone methyltransferase SET-domain-containing 2 (SETD2), which is responsible for H3 lysine 36 trimethylation (H3K36me3) of histones, also methylates α-tubulin at lysine 40, the same lysine that is marked by acetylation on microtubules. Methylation of microtubules occurs during mitosis and cytokinesis and can be ablated by SETD2 deletion, which causes mitotic spindle and cytokinesis defects, micronuclei, and polyploidy	SIGNOR-269090
P49354	O14807	1	null	up-regulates activity	0.2	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-242553
Q13813	O15287	0	null	up-regulates quantity by stabilization	0.367	In FA cells, deficiencies in FA proteins lead to decreased stability of alphaRIISp \|These results demonstrate that one of the FA proteins, FANCG, contains a motif that interacts directly with the SH3 domain of alphaIISp. We propose that this binding of FANCG to alphaIISp may be important for the stability of alphaIISp in cells and the role alphaIISp plays in the DNA repair process.\|	SIGNOR-263275
O00459	P22681	0	ubiquitination	down-regulates	0.606	Cbl-b, a ring-type e3 ubiquitin protein ligase, is implicated in setting the threshold of t lymphocyte activation. The p85 regulatory subunit of phosphatidylinositol 3 kinase (pi3k) was identified as a substrate for cbl-b. We have shown that cbl-b negatively regulated p85 in a proteolysis-independent manner.	SIGNOR-110063
Q16665	Q9Y4C1	1	transcriptional regulation	up-regulates quantity by expression	0.415	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271568
P56524	Q13131	0	phosphorylation	down-regulates	0.272	We show here that in liver, class iia hdacs (hdac4, 5, and 7) are phosphorylated and excluded from the nucleus by ampk family kinases.	SIGNOR-173689
Q13043	P42336	1	phosphorylation	down-regulates activity	0.2	MST1/2 and HGK inhibit catalytic activity of p110α through phosphorylation at T1061	SIGNOR-277920
P12931	O75553	1	phosphorylation	up-regulates activity	0.42	Dab1 is rapidly phosphorylated when neurons isolated from embryonic brains are stimulated with Reelin, and several tyrosines have been implicated in this response. Mice with phenylalanine substitutions of all five tyrosines (Tyr(185), Tyr(198), Tyr(200), Tyr(220), and Tyr(232)) exhibit a reeler phenotype, implying that tyrosine phosphorylation is critical for Dab1 function. Here we report that, although Src can phosphorylate all five tyrosines in vitro, Tyr(198) and Tyr(220) represent the major sites of Reelin-induced Dab1 phosphorylation in embryonic neurons.	SIGNOR-247080
P78352	Q5JU85	0	relocalization	up-regulates activity	0.472	Here, we characterized IQ-ArfGEF/BRAG1, a guanine nucleotide exchange factor (GEF) for Arf6, in the mouse brain. In vivo Arf pull down assay demonstrated that IQ-ArfGEF/BRAG1 activated Arf6 more potently than Arf1.IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses. Taken together, IQ-ArfGEF/BRAG1 forms a postsynaptic protein complex containing PSD-95 and NMDA receptors at excitatory synapses, where it may function as a GEF for Arf6.	SIGNOR-264907
P60484	P06239	0	phosphorylation	up-regulates	0.374	Thus, y240a and y315a are involved in the ability of mmac/pten to dephosphorylate ptdins and regulate tumor cell growth in vitro and in vivo.	SIGNOR-116499
P53671	Q15672	1	phosphorylation	up-regulates quantity	0.2	LIMK2 directly phosphorylated TWIST1, indicating that LIMK2 also regulates TWIST1 post-translationally (XREF_FIG).\|LIMK2 positively regulates TWIST1 protein levels.	SIGNOR-278952
O43379	Q9Y3I1	0	ubiquitination	down-regulates quantity by destabilization	0.2	WDR62 is also negatively regulated by T1053 phosphorylation, leading to the recruitment of F-box and WD repeat domain-containing protein 7 (FBW7) and proteasomal degradation. \|JNK1 can induce the phosphorylation of WDR62 T1053	SIGNOR-271711
Q9BR76	Q8WYL5	0	dephosphorylation	up-regulates	0.446	Coronin 1b inhibits filament nucleation by arp2/3 complex and this inhibition is attenuated by phosphorylation of coronin 1b at serine 2, a site targeted by ssh1l.	SIGNOR-153604
P12931	Q07954	1	phosphorylation	up-regulates activity	0.394	We recently observed that the ldl receptor-related protein 1 (lrp-1) is tyrosine phosphorylated in v-src-transformed cells.Of the four tyrosine residues present in the cytoplasmic domain of lrp-1, only tyr 63 is phosphorylated by v-src in vivo or in vitro. Using fibroblasts deficient in src, yes and fyn, we were able to show that there are multiple kinases present in the cell that can phosphorylate lrp-1. Tyrosine-phosphorylated lrp-1 associates with shc, a ptb and sh2 domain containing signaling protein that is involved in the activation of ras	SIGNOR-101535
Q15306	O75116	0	phosphorylation	up-regulates	0.417	Carock2 phosphorylated irf4 at either of 2 distinct phosphorylation sites, s446 and s447 / rock2-mediated phosphorylation of irf4 regulated the synthesis of il-17 and il-21 and the differentiation of th17 cells.	SIGNOR-167471
Q9UQM7	O95997	1	phosphorylation	down-regulates quantity by destabilization	0.309	CaMKII phosphorylates securin at PP2A substrate site(s).Securin is destabilized by phosphorylation and stabilized by PP2A-dependent dephosphorylation on separase	SIGNOR-276381
Q07869	Q7Z6Z7	0	ubiquitination	down-regulates quantity by destabilization	0.2	Furthermore, the E3 ubiquitin ligase HUWE1 was identified to mediate PPARalpha polyubiquitination.\|This notion is also supported by our finding that Huwe1 knockdown up-regulated the expression of PPARalpha target genes at the cellular level.	SIGNOR-278814
Q96CG3	Q96QP1	0	phosphorylation	up-regulates activity	0.247	The authors proposed that binding of ADP-Hep caused a conformational change exposing the catalytic cleft and allowing for ALPK1 to phosphorylate and activate TIFA leading to downstream NF-kB activation.	SIGNOR-279789
Q07912	O00401	1	phosphorylation	up-regulates activity	0.307	Because TNK2 phosphorylation of WASL increases its actin nucleation activity ( xref ), we reasoned that it might be possible to complement the TNK2 deficiency by overexpression of WASL.\|For NCK1, based on its reported binding to WASL and TNK2, we hypothesized that its function is to recruit WASL to TNK2, which could then activate WASL via phosphorylation ( xref ; xref ).	SIGNOR-280155
P46934	P07948	1	polyubiquitination	down-regulates quantity by destabilization	0.459	These findings suggest that LMP2A recruits Nedd4-like ubiquitin-protein ligases and B-cell signal transduction molecules, resulting in the degradation of LMP2A and Lyn by a ubiquitin-dependent mechanism.	SIGNOR-272558
Q13315	Q4G0J3	1	phosphorylation	down-regulates quantity by destabilization	0.2	Altogether, the results suggest that ATM-mediated T440 phosphorylation enhances LARP7-BARD1 interaction and facilitates BRCA1/BARD1-mediated LARP7 ubiquitination and degradation.	SIGNOR-275580
P17252	P04049	1	phosphorylation	down-regulates	0.558	Pka can inhibit raf-1 function directly via phosphorylation of the raf-1 kinase domain	SIGNOR-34761
P61224	P17612	0	phosphorylation	up-regulates	0.522	These results provide a mechanistic explanation for the differential effects of rap1 phosphorylation by pka on effector protein interaction. camp is one among several pathways leading to rap1 activation	SIGNOR-187410
P22459	Q8TBB1	0	ubiquitination	down-regulates quantity by destabilization	0.283	We used the Ligand of Numb protein X (LNX) family of E3s, a group of PDZ domain-containing RING-type E3 ubiquitin ligases, to demonstrate the feasibility of this strategy. Many potential substrates of LNX E3s were identified. Eight of the nine selected candidates were ubiquitinated in vitro, and two novel endogenous substrates, PDZ-binding kinase (PBK) and breakpoint cluster region protein (BCR), were confirmed in vivo.The C-terminal LNX1 PDZ1-binding motifs of the ATP-binding cassette, subfamily A member 1 (ABC-1), PBK, glutamate receptor, ionotropic, N-methyl d-aspartate 1 (GRIN1), and Claudin-17 significantly promoted the ubiquitination of the corresponding artificial degrons by LNX1ΔPDZ234.	SIGNOR-272899
P01106	Q13627	0	phosphorylation	down-regulates quantity	0.374	We also found that DYRK1A phosphorylated c-Myc on Ser62, priming phosphorylation on Thr58 by GSK3\u03b2 and subsequent degradation.\|c-Myc expression is down-regulated by DYRK1A.	SIGNOR-279609
Q92574	P54646	0	phosphorylation	up-regulates	0.551	Under energy starvation conditions, the amp-activated protein kinase (ampk) phosphorylates tsc2 and enhances its activity.	SIGNOR-119541
P16519	P01189-PRO_0000024969	1	cleavage	up-regulates quantity	0.2	POMC is post-translationally cleaved by prohormone convertase enzymes 1 and 2 (PC1, PC2) into ACTH, an N-terminal glycopeptide	SIGNOR-268725
O60341	Q16695	1	demethylation	up-regulates activity	0.2	Here, we provide evidence that LSD1 (KIAA0601), a nuclear homolog of amine oxidases, functions as a histone demethylase and transcriptional corepressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription.	SIGNOR-264508
Q04206	O14920	0	phosphorylation	up-regulates activity	0.886	Rela is phosphorylated at ser536 by ikkbeta, ikkalfa, ikkepsilon, nf-kb activating kinase (nak, also known as tank-binding kinase-1 tbk1) and rsk1 (also known as p90 ribosomal protein s6 kinase (p90s6k). We now present evidence that suggests that the upstream kinase ikkbeta plays an important role in tax-induced p53 inhibition through phosphorylation of p65/rela at ser-536. Ikkbeta plays an important role in tax-induced p53 inhibition through phosphorylation of p65/rela at ser-536.	SIGNOR-138903
Q05513	P52565	1	phosphorylation	up-regulates activity	0.246	Hence, it may be reasonable to deduce that N-formyl-methionyl-leucyl-phenylalanine binds its receptors to activate protein kinase C\u03b6 to generate superoxide, which in turn stimulates the motility in an autocrine manner via the protein kinase C\u03b6-RhoGDI-1-RhoGTPase pathway.\|In these cells, protein kinase C zeta was activated to phosphorylate RhoGDI-1, which liberated RhoGTPases, leading to their activation.	SIGNOR-280089

P16949

P28482

0

phosphorylation

down-regulates

0.452

Involved in the regulation of the microtubule (mt) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. The kinases involved in phosphorylating stmn ser-16 and ser-63 include camp-dependent protein kinase (pka) and pak1, whereas stmn ser-25 and ser-38 have been shown to be targets for proline-directed serine/threonine kinases such as cyclin-dependent kinases, erk1/2, and members of the p38 mapk subfamily.

SIGNOR-166686

O43318

Q15653

1

phosphorylation

down-regulates

0.515

Overexpression oftak1together with its activator protein,tak1binding protein 1 (tab1), induced thenucleartranslocation of nf-kappa b p50/p65 heterodimer accompanied by the degradation of i kappa b alpha and i kappa b beta, and the expression of kappa b-dependent reporter gene.

SIGNOR-55719

P67809

P78527

0

phosphorylation

up-regulates activity

0.338

The DNA-PK subunits and YB-1 phosphorylated at T89 were found colocalized suggesting their in vivo interaction.DNA-PK directly phosphorylates YB-1 and, this way, modulates YB-1 function. Point mutation of YB-1 at this residue abrogated the translocation of YB-1 into the nucleus.

SIGNOR-277611

P31943

P12931

1

post transcriptional regulation

up-regulates quantity by expression

0.291

HnRNP H is a component of a splicing enhancer complex that activates a c-src alternative exon in neuronal cells.

SIGNOR-261273

P28482

Q9BQQ3

1

phosphorylation

down-regulates activity

0.27

Here we show that GRASP65 is phosphorylated on serine 277 in interphase cells, and this is strongly enhanced in response to the addition of serum or epidermal growth factor. This is directly mediated by ERK suggesting that GRASP65 has some role in growth factor signal transduction. These results argue against Ser-277 phosphorylation alone causing the dissolution of GRASP65 oligomers and cisternal unstacking, although it may make a significant contribution to these events.

SIGNOR-262841

Q03112

Q00526

0

phosphorylation

up-regulates activity

0.2

The motif harbouring S436 is a target of CDK2 and CDK3 kinases, which interacted with EVI1-WT. The methyltransferase DNMT3A bound preferentially to EVI1-WT compared with EVI1-S436A, and a hypomethylated cell population associated by EVI1-WT expression in murine haematopoietic progenitors is not maintained with EVI1-S436A.

SIGNOR-273431

P06241

Q05655

1

phosphorylation

up-regulates activity

0.597

In conclusion, our in vitro data and previous report ( xref ) demonstrate that Fyn phosphorylation of Y311 on PKC\u03b4 activates the apoptotic signaling cascade in DAergic neurons in response to neurotoxic insults.

SIGNOR-279737

O15350

O15111

0

phosphorylation

up-regulates activity

0.336

IKK-alpha had an ability to stabilize p73 by inhibiting its polyubiquitination, and enhanced p73 mediated transcriptional activation as well as proapoptotic activity.|In addition, IKK-alpha phosphorylated the NH 2 -terminal portion of p73 and a kinase deficient mutant form of IKK-alpha had undetectable effect on p73.

SIGNOR-279697

Q96QF0

Q15208

0

phosphorylation

up-regulates activity

0.366

We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation.

SIGNOR-263036

P19174

P17612

0

phosphorylation

down-regulates

0.2

The observation that pka also phosphorylates plc-yl on serine 1248 suggests that phosphorylation of this residue may be a common mechanism by which pkc and pka inhibit plc-yl.

SIGNOR-17901

P10636-2

P17252

0

phosphorylation

down-regulates activity

0.265

We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.

SIGNOR-275441

P07196

P17612

0

phosphorylation

down-regulates activity

0.2

Phosphorylation of neurofilament-L protein (NF-L) by the catalytic subunit of cAMP-dependent protein kinase (A-kinase) inhibits the reassembly of NF-L and disassembles filamentous NF-L.

SIGNOR-252401

P07225

P38435

0

carboxylation

up-regulates activity

0.613

Gamma-carboxylation is essential in the activation and proper functioning of multiple VK-dependent proteins (VKDP), the most well-known of which are involved in blood clotting, including coagulation factors (FII, FVII, FIX and FX) and natural anti-clotting agents (protein C, protein S (ProS; OMIM*176880) and protein Z

SIGNOR-265924

P17676

P35247

1

transcriptional regulation

up-regulates quantity by expression

0.251

Cotransfection of C/EBPalpha, C/EBPbeta, or C/EBPdelta cDNA in H441 lung adenocarcinoma cells significantly increased the luciferase activity of a wild-type SP-D promoter construct containing 698 bp of upstream sequence (SS698). Transfection of C/EBP also increased the level of endogenous SP-D mRNA in H441 cells| Thus, interactions among C/EBP elements in the near-distal promoter can modulate the promoter activity of SP-D.

SIGNOR-254045

Q16827

P07948

1

dephosphorylation

down-regulates activity

0.325

Both Lyn and ZAP70 were dephosphorylated by wild-type PTPROt, but not by its catalytic site mutant.|Lyn kinase and ZAP70 are substrates of PTPROt in B-cells: Lyn inactivation by PTPROt sensitizes leukemia cells to VEGF-R inhibitor pazopanib.

SIGNOR-277144

P68400

P08047

1

phosphorylation

down-regulates activity

0.34

Casein kinase II-mediated phosphorylation of the C terminus of Sp1 decreases its DNA binding activity. | Mutation of a consensus CKII site at amino acid 579, within the second zinc finger, eliminates phosphorylation of this site and the CKII-mediated inhibition of Sp1 binding.

SIGNOR-250954

O75365

P05787

1

dephosphorylation

down-regulates activity

0.272

the cytoskeletal intermediate filament keratin 8 (KRT8) was identified as a physiological PRL-3-interacting protein. Indeed, treatment with the PRL-3 inhibitor effectively suppressed the phosphorylation of KRT8 at S73 and S431

SIGNOR-248341

P40763

P01189

1

transcriptional regulation

up-regulates quantity by expression

0.638

We show that phospho-STAT3 activates POMC promoter in response to leptin signaling through a mechanism that requires an SP1-binding site in the POMC promoter.

SIGNOR-263497

Q9P0L2

P11137

1

phosphorylation

down-regulates activity

0.418

Here we show that p110mark phosphorylates analogous KXGS sites in the microtubule binding domains of the neuronal MAP2 and the ubiquitous MAP4. Phosphorylation in vitro leads to the dissociation of MAP2 and MAP4 from microtubules and to a pronounced increase in dynamic instability.

SIGNOR-250166

P29353

P17706

0

dephosphorylation

down-regulates activity

0.572

However, TC45 inhibited the EGF-induced association of p52Shc with Grb2, which was attributed to the ability of the PTP to recognize specifically p52Shc phosphorylated on Y239. These results indicate that TC45 recognizes not only selected substrates in a cellular context but also specific sites within substrates and thus may regulate discrete signaling events.

SIGNOR-248397

P0C5Z0

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265407

P35222

P51955

0

phosphorylation

down-regulates quantity

0.469

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

SIGNOR-278173

Q96GF1

O14641

1

polyubiquitination

down-regulates quantity by destabilization

0.466

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

SIGNOR-272173

P68431

Q9UQB9

0

phosphorylation

up-regulates activity

0.2

Phosphorylation at ser-11 (h3s10ph) by aurkb is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. Phosphorylation at ser-11 (h3s10ph) by aurkb is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis.

SIGNOR-118898

Q12959

Q9UQM7

0

phosphorylation

down-regulates activity

0.649

Synapse-associated protein 97 (SAP97), a member of membrane-associated guanylate kinase protein family, has been implicated in the processes of targeting ionotropic glutamate receptors at postsynaptic sites. | We show here that SAP97 is directly associated with NR2A through its PDZ1 domain, and CaMKII-dependent phosphorylation of SAP97-Ser-232 disrupts NR2A interaction both in an in vitro pull-out assay and in transfected COS-7 cells. Moreover, expression of SAP97(S232D) mutant has effects similar to those observed upon constitutively activating CaMKII.

SIGNOR-250618

O14757

Q06609

1

phosphorylation

up-regulates

0.843

We demonstrate that chk1 interacts with rad51, and that rad51 is phosphorylated on thr 309 in a chk1-dependent manner

SIGNOR-133375

P35637

P57678

1

relocalization

up-regulates activity

0.2

Here, we report that FUS associates with the SMN complex, mediated by U1 snRNP and by direct interactions between FUS and SMN.|The FUS IP and pulldown revealed that FUS also associates with components of the SMN complex, including SMN and Gemins 4 and 6 |Remarkably, the number of SMN-stained nuclear bodies was dramatically reduced in the FUS knockdown cells

SIGNOR-262105

P11802

P30304

0

dephosphorylation

up-regulates activity

0.705

Invalidation of CDK4 has no impact by itself on the cell proliferation, but invalidation of CDC25A prevents the dephosphorylation of CDK6 (Y24) and CDK4 (Y17) residues, and impedes their association with CCNDs.

SIGNOR-267568

P52564

Q14765

1

phosphorylation

up-regulates activity

0.342

MKK6, phosphorylate STAT4 on serine 721. IL-12 induces STAT4 phosphorylation on serine 721 and that mutation of serine 721 interferes with STAT4 transcriptional activity.

SIGNOR-251425

O75534

P01100

1

post transcriptional regulation

down-regulates quantity

0.295

By testing different classes of mammalian poly(A) nucleases, we identified CCR4 as a poly(A) nuclease involved in the mCRD-mediated rapid deadenylation in viv

SIGNOR-261145

P11309

P31269

0

transcriptional regulation

up-regulates quantity by expression

0.2

Thus Pim1 appears to be a direct transcriptional target of HOXA9 and a mediator of its antiapoptotic and proproliferative effects in early cells.

SIGNOR-261632

Q6AZZ1

Q92734

1

ubiquitination

down-regulates quantity by destabilization

0.451

Our results suggest that TRIM68 degrades TFG at a point of pathway convergence in which downstream events lead to the activation of both NF-kappaB and IRF3.|TRIM68 polyubiquitinates TFG leading to its degradation via its RING domain which also plays an important role in TRIM68 negative inhibition on IFN-beta production.

SIGNOR-278737

P17252

P41594

1

phosphorylation

up-regulates activity

0.416

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

SIGNOR-249278

Q5VT25

Q9BZL4

1

phosphorylation

down-regulates activity

0.558

Identification of the Phosphorylation Site of p85 on Threonine 560 by MRCKα-CAT | Wild-type p85 but not the mutant p85AA, when phosphorylated in vitro with MRCKα-CAT, showed significant reduction in the rate of MLC2 dephosphorylation. These results confirm a similar observation with MBS130 where phosphorylation of a conserved threonine 695 within a highly conserved motif was essential for the inhibition of phosphatase catalytic activity

SIGNOR-250724

P05204

P51812

0

phosphorylation

down-regulates activity

0.29

We report here that the NBD of the HMGN1 and -N2 protein family is highly and specifically phosphorylated during mitosis and that this phosphorylation has a major functional consequence: it abolishes the interaction of the proteins with its chromatin targets.

SIGNOR-249102

P11142

O75061

0

relocalization

up-regulates activity

0.883

Hsc70, recruited by the J-domain protein auxilin, mediates clathrin uncoating and release of a free vesicle, primed to fuse with a target membrane.

SIGNOR-260719

P37231

Q9UBK2

1

transcriptional regulation

up-regulates quantity by expression

0.903

NFIA binds to and activates the brown-fat-specific enhancers even before differentiation and later facilitates the binding of PPARgamma|NFIA has at least three functions on the transcriptional regulation of brown fat [2]. First, NFIA activates adipogenesis per se, through activating the transcription of Pparg, which encodes PPARgamma. Second, NFIA also activates the brown-fat-specific gene expression (such as Ucp1 and Ppargc1a) independent of the degree of adipocyte differentiation, through facilitating the binding of PPARgamma to the brown-fat-specific enhancers. Third, NFIA represses myogenesis through suppression of myogenic transcription factors such as Myod1 as well as Myog,

SIGNOR-263984

Q13490

Q13546

1

polyubiquitination

up-regulates activity

0.768

CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.

SIGNOR-272710

A1A4S6

P61586

1

gtpase-activating protein

down-regulates activity

0.668

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-260465

Q09013

P26678

1

phosphorylation

up-regulates

0.54

Coimmunoprecipitation studies showed that dmpk and pln can physically associate. Furthermore, purified wild-type dmpk, but not a kinase-deficient mutant (k110a dmpk), phosphorylates pln in vitro

SIGNOR-131371

P06493

Q9Y6I3

1

phosphorylation

down-regulates activity

0.323

Phosphorylation of POB1 and Epsin by p34cdc2 kinase. Their phosphorylation sites (Ser411 of POB1 and Ser357 of Epsin) were determined. Phosphorylated Epsin and EpsinS357D formed a complex with α-adaptin less efficiently than wild type Epsin.

SIGNOR-262723

P28482

Q9Y463

1

phosphorylation

up-regulates activity

0.369

S421 resides within a Ser-Pro phosphoacceptor motif that is typical for ERK1/2 and recombinant ERK2 phosphorylated DYRK1B at S421 in vitro.

SIGNOR-276937

P00533

O60674

0

phosphorylation

up-regulates activity

0.612

Tyrosine at residue 1,068 of the EGFR is proposed to be one of the principal phosphorylation sites and Grb2-binding sites stimulated by growth hormone via Jak2. Our results indicate that the role of EGFR in signalling by growth hormone is to be phosphorylated by Jak2, thereby providing docking sites for Grb2 and activating MAP kinases and gene expression, independently of the intrinsic tyrosine kinase activity of EGFR.¬†

SIGNOR-251347

P45983

P45985

0

phosphorylation

up-regulates activity

0.752

Stress-activated protein kinase 1 (SAPK1), also called c-Jun N-terminal kinase (JNK), becomes activated in vivo in response to pro-inflammatory cytokines or cellular stresses. Its full activation requires the phosphorylation of a threonine and a tyrosine residue in a Thr-Pro-Tyr motif, which can be catalysed by the protein kinases mitogen-activated protein kinase kinase (MKK)4 and MKK7. Here we report that MKK4 shows a striking preference for the tyrosine residue (Tyr-185), and MKK7 a striking preference for the threonine residue (Thr-183) in three SAPK1/JNK1 isoforms tested (JNK1 alpha 1, JNK2 alpha 2 and JNK3 alpha 1).

SIGNOR-251419

O15355

P84103

1

dephosphorylation

down-regulates activity

0.2

Here, we found that the PPM1G regulated SRSF3, and high levels of PPM1G decreased SRSF3 activity in HCC cells.|PPM1G interacted with SRSF3 and dephosphorylated SRSF3.

SIGNOR-277048

O75496

O43791

0

ubiquitination

down-regulates activity

0.2

SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. This poly-ubiquitination of Geminin prevents DNA replication over-firing by indirectly blocking the association of Cdt1 with the MCM protein complex, an interaction required for DNA unwinding and replication.

SIGNOR-268926

P55212

O60285

0

phosphorylation

down-regulates activity

0.483

ARK5 negatively regulates procaspase-6 by phosphorylation at Ser257, leading to resistance to the FasL/Fas system.

SIGNOR-250209

Q9ULK5

Q01974

0

phosphorylation

down-regulates activity

0.59

In support of this, ror2 mutants abolish Vangl2 activity gradient and localization, and ror2; vangl2 double mutants phenocopy the wnt5a limb phenotype (Gao et al., 2011).4.6.|This process is mediated by its receptor Ror2, which in turn phosphorylates Vangl2 and induces asymmetric localization of Vangl2, propagating an activity gradient of Vangl2 in the proximal direction (Gao et al., 2011).

SIGNOR-280111

P49137

P27361

0

phosphorylation

up-regulates

0.475

Erk phosphorylates multiple cytoplasmatic and cytoskeletal proteins, including mapk-activated protein kinases and the ribosomal p70-s6 kinase

SIGNOR-201687

P17405

Q05655

0

phosphorylation

up-regulates

0.256

Activation of acid sphingomyelinase by protein kinase cdelta-mediated phosphorylation. Phosphorylation of ser(508) proved to be an indispensable step for asmase activation and membrane translocation in response to pma

SIGNOR-153276

P04637

O43474

0

transcriptional regulation

down-regulates quantity by repression

0.56

Previous work has shown that the Kruppel-like factor 4 (KLF4) transcription factor represses p53 transcription by binding to the PE21 element.

SIGNOR-270544

P48426

Q15139

0

phosphorylation

down-regulates

0.2

We conclude that the type ii pip kinases are physiological targets for pkd phosphorylation, and that this modification is likely to regulate inositol lipid turnover by inhibition of these lipid kinases.

SIGNOR-145370

Q02548

P28482

0

phosphorylation

down-regulates activity

0.351

In this study, we demonstrated that PAX5 was phosphorylated by ERK1/2 in vitro and in vivo at serines 189 and 283. This phosphorylation attenuated the transcriptional repression of BLIMP1 by PAX5.

SIGNOR-269087

Q9BXF3

Q9UJQ4

0

transcriptional regulation

up-regulates quantity by expression

0.2

SALL4 activates Cecr2 by directly binging to its promotor region and CECR2 in turn promotes reprogramming through forming a SMARCA1-contained chromatin remodeling complex with its DTT domain.

SIGNOR-263893

O75925

P17844

1

sumoylation

up-regulates

0.546

We demonstrate that the sumo e3 ligase pias1 interacts with p68 and enhances its sumo modification in vivo / sumo modification enhances p68 transcriptional repression activity and inhibits the ability of p68 to function as a coactivator of p53.

SIGNOR-153719

O75116

P05067

1

phosphorylation

up-regulates quantity

0.386

Moreover, SR3677 blocked ROCK2 phosphorylation of APP at threonine 654 (T654); in neurons, T654 was critical for APP processing to Abeta.|These observations suggest that ROCK2 inhibition reduces Abeta levels through independent mechanisms.

SIGNOR-280109

Q13469

P49841

0

phosphorylation

down-regulates

0.561

Gsk3 was previously shown to directly phosphorylate the n-terminal regulatory domain of nfatc1, thus antagonizing the action of calcineurin and inhibiting nuclear shuttling of nfat.

SIGNOR-179784

Q9Y4K3

P04637

1

ubiquitination

up-regulates activity

0.61

Here, we show that TRAF6 E3 ligase is a crucial factor to restrict mitochondrial translocation of p53 and spontaneous apoptosis by promoting K63-linked ubiquitination of p53 at K24 in cytosol, and such ubiquitination limits the interaction between p53 and MCL-1/BAK.|We mutated every conserved lysine (K) residue on p53 and found that TRAF6 preferentially ubiquitinates p53 at K24 in the in vivo ubiquitination assay (XREF_FIG, XREF_SUPPLEMENTARY, XREF_SUPPLEMENTARY and XREF_SUPPLEMENTARY).

SIGNOR-278728

P01024

P17676

0

transcriptional regulation

up-regulates quantity by expression

0.259

CCAAT/enhancer binding protein β directly regulates the expression of the complement component 3 gene in neural cells: implications for the pro-inflammatory effects of this transcription factor

SIGNOR-261927

Q3MIX3

P48436

1

phosphorylation

up-regulates activity

0.2

Here we investigated the mechanism of ADCK5 involved in regulating invasion and migration of lung cancer cells, and showed that ADCK5 might regulate the expression of tumor oncogene human pituitary tumor transforming gene-1 (PTTG1) by phosphorylating transcription factor SOX9|Mutagenesis of potential serine phosphorylation sites on SOX9 indicated that serine 181 might be required to maintain transcription activation of SOX9 as well as increase PTTG1 levels.

SIGNOR-264567

Q13153

P17600

1

phosphorylation

up-regulates activity

0.349

Synapsin I is phosphorylated at Ser603 by p21-activated kinases. the Ser603 residue must be one of the pivotal sites for the release

SIGNOR-250235

O95816

P49137

0

phosphorylation

up-regulates

0.366

We provided definite evidence that mapkapk2 phosphorylates bag2 at ser 20 in vitro and in vivo. These results demonstrate that bag2 is a novel component of the p38 mapk signaling pathways.

SIGNOR-126953

P60953

P12931

0

phosphorylation

up-regulates

0.695

Epidermal growth factor-dependent regulation of cdc42 is mediated by the src tyrosine kinaseegf signaling through src appears to have dual regulatory effects on cdc42: 1). it leads to the activation of cdc42 as mediated by the vav2 guanine nucleotide exchange factor, and 2). it results in the phosphorylation of cdc42, which stimulates the binding of rhogdi, perhaps to direct the movement of cdc42 to a specific cellular site to trigger a signaling response, because cdc42-rhogdi interactions are essential for cdc42-induced cellular transformation.

SIGNOR-118206

P16885

P08631

0

phosphorylation

up-regulates activity

0.552

The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors.

SIGNOR-249364

Q05513

P28329

1

phosphorylation

up-regulates

0.288

Finally, basal chat phosphorylation in neurons is mediated predominantly by pkc at ser-476, with pkc activation increasing phosphorylation at ser-440 and enhancing chat activity.

SIGNOR-129340

O75385

P14373

0

ubiquitination

down-regulates quantity

0.2

STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination

SIGNOR-270349

Q13043

P22455

0

phosphorylation

down-regulates activity

0.2

FGFR4 phosphorylates MST1 to confer breast cancer cells resistance to MST1/2 dependent apoptosis.|We provide evidence suggesting that by Y433-MST1 phosphorylation , FGFR4 inhibits MST1 / 2 activation .

SIGNOR-279714

P29466

P49810

1

cleavage

up-regulates activity

0.32

In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329.

SIGNOR-261748

P43354

P28482

0

phosphorylation

up-regulates

0.395

We have shown that erk2 is a kinase to phosphorylate nurr1 on multiple sites. S126 and t132, which are located near af1 core of nurr1, are dominant sites phosphorylated by erk2. reporter gene assays show that nurr1delta124-133/t185a, an erk2 phospho-site mutant form, could not further increase its transcriptional activity on th promoter, suggesting that nurr1 phosphorylation by erk2 may regulate its transcriptional activity on th promoter.

SIGNOR-157167

P36507

P55211

1

phosphorylation

down-regulates activity

0.347

Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK|The opposing protein kinase activity is overcome by treatment with the broad-specificity kinase inhibitor staurosporine or with inhibitors of MEK1/2

SIGNOR-249386

Q9BYW2

P68363

1

methylation

up-regulates activity

0.244

The histone methyltransferase SET-domain-containing 2 (SETD2), which is responsible for H3 lysine 36 trimethylation (H3K36me3) of histones, also methylates α-tubulin at lysine 40, the same lysine that is marked by acetylation on microtubules. Methylation of microtubules occurs during mitosis and cytokinesis and can be ablated by SETD2 deletion, which causes mitotic spindle and cytokinesis defects, micronuclei, and polyploidy

SIGNOR-269090

P49354

O14807

1

null

up-regulates activity

0.2

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-242553

Q13813

O15287

0

null

up-regulates quantity by stabilization

0.367

In FA cells, deficiencies in FA proteins lead to decreased stability of alphaRIISp |These results demonstrate that one of the FA proteins, FANCG, contains a motif that interacts directly with the SH3 domain of alphaIISp. We propose that this binding of FANCG to alphaIISp may be important for the stability of alphaIISp in cells and the role alphaIISp plays in the DNA repair process.|

SIGNOR-263275

O00459

P22681

0

ubiquitination

down-regulates

0.606

Cbl-b, a ring-type e3 ubiquitin protein ligase, is implicated in setting the threshold of t lymphocyte activation. The p85 regulatory subunit of phosphatidylinositol 3 kinase (pi3k) was identified as a substrate for cbl-b. We have shown that cbl-b negatively regulated p85 in a proteolysis-independent manner.

SIGNOR-110063

Q16665

Q9Y4C1

1

transcriptional regulation

up-regulates quantity by expression

0.415

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271568

P56524

Q13131

0

phosphorylation

down-regulates

0.272

We show here that in liver, class iia hdacs (hdac4, 5, and 7) are phosphorylated and excluded from the nucleus by ampk family kinases.

SIGNOR-173689

Q13043

P42336

1

phosphorylation

down-regulates activity

0.2

MST1/2 and HGK inhibit catalytic activity of p110α through phosphorylation at T1061

SIGNOR-277920

P12931

O75553

1

phosphorylation

up-regulates activity

0.42

Dab1 is rapidly phosphorylated when neurons isolated from embryonic brains are stimulated with Reelin, and several tyrosines have been implicated in this response. Mice with phenylalanine substitutions of all five tyrosines (Tyr(185), Tyr(198), Tyr(200), Tyr(220), and Tyr(232)) exhibit a reeler phenotype, implying that tyrosine phosphorylation is critical for Dab1 function. Here we report that, although Src can phosphorylate all five tyrosines in vitro, Tyr(198) and Tyr(220) represent the major sites of Reelin-induced Dab1 phosphorylation in embryonic neurons.

SIGNOR-247080

P78352

Q5JU85

0

relocalization

up-regulates activity

0.472

Here, we characterized IQ-ArfGEF/BRAG1, a guanine nucleotide exchange factor (GEF) for Arf6, in the mouse brain. In vivo Arf pull down assay demonstrated that IQ-ArfGEF/BRAG1 activated Arf6 more potently than Arf1.IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses. Taken together, IQ-ArfGEF/BRAG1 forms a postsynaptic protein complex containing PSD-95 and NMDA receptors at excitatory synapses, where it may function as a GEF for Arf6.

SIGNOR-264907

P60484

P06239

0

phosphorylation

up-regulates

0.374

Thus, y240a and y315a are involved in the ability of mmac/pten to dephosphorylate ptdins and regulate tumor cell growth in vitro and in vivo.

SIGNOR-116499

P53671

Q15672

1

phosphorylation

up-regulates quantity

0.2

LIMK2 directly phosphorylated TWIST1, indicating that LIMK2 also regulates TWIST1 post-translationally (XREF_FIG).|LIMK2 positively regulates TWIST1 protein levels.

SIGNOR-278952

O43379

Q9Y3I1

0

ubiquitination

down-regulates quantity by destabilization

0.2

WDR62 is also negatively regulated by T1053 phosphorylation, leading to the recruitment of F-box and WD repeat domain-containing protein 7 (FBW7) and proteasomal degradation. |JNK1 can induce the phosphorylation of WDR62 T1053

SIGNOR-271711

Q9BR76

Q8WYL5

0

dephosphorylation

up-regulates

0.446

Coronin 1b inhibits filament nucleation by arp2/3 complex and this inhibition is attenuated by phosphorylation of coronin 1b at serine 2, a site targeted by ssh1l.

SIGNOR-153604

P12931

Q07954

1

phosphorylation

up-regulates activity

0.394

We recently observed that the ldl receptor-related protein 1 (lrp-1) is tyrosine phosphorylated in v-src-transformed cells.Of the four tyrosine residues present in the cytoplasmic domain of lrp-1, only tyr 63 is phosphorylated by v-src in vivo or in vitro. Using fibroblasts deficient in src, yes and fyn, we were able to show that there are multiple kinases present in the cell that can phosphorylate lrp-1. Tyrosine-phosphorylated lrp-1 associates with shc, a ptb and sh2 domain containing signaling protein that is involved in the activation of ras

SIGNOR-101535

Q15306

O75116

0

phosphorylation

up-regulates

0.417

Carock2 phosphorylated irf4 at either of 2 distinct phosphorylation sites, s446 and s447 / rock2-mediated phosphorylation of irf4 regulated the synthesis of il-17 and il-21 and the differentiation of th17 cells.

SIGNOR-167471

Q9UQM7

O95997

1

phosphorylation

down-regulates quantity by destabilization

0.309

CaMKII phosphorylates securin at PP2A substrate site(s).Securin is destabilized by phosphorylation and stabilized by PP2A-dependent dephosphorylation on separase

SIGNOR-276381

Q07869

Q7Z6Z7

0

ubiquitination

down-regulates quantity by destabilization

0.2

Furthermore, the E3 ubiquitin ligase HUWE1 was identified to mediate PPARalpha polyubiquitination.|This notion is also supported by our finding that Huwe1 knockdown up-regulated the expression of PPARalpha target genes at the cellular level.

SIGNOR-278814

Q96CG3

Q96QP1

0

phosphorylation

up-regulates activity

0.247

The authors proposed that binding of ADP-Hep caused a conformational change exposing the catalytic cleft and allowing for ALPK1 to phosphorylate and activate TIFA leading to downstream NF-kB activation.

SIGNOR-279789

Q07912

O00401

1

phosphorylation

up-regulates activity

0.307

Because TNK2 phosphorylation of WASL increases its actin nucleation activity ( xref ), we reasoned that it might be possible to complement the TNK2 deficiency by overexpression of WASL.|For NCK1, based on its reported binding to WASL and TNK2, we hypothesized that its function is to recruit WASL to TNK2, which could then activate WASL via phosphorylation ( xref ; xref ).

SIGNOR-280155

P46934

P07948

1

polyubiquitination

down-regulates quantity by destabilization

0.459

These findings suggest that LMP2A recruits Nedd4-like ubiquitin-protein ligases and B-cell signal transduction molecules, resulting in the degradation of LMP2A and Lyn by a ubiquitin-dependent mechanism.

SIGNOR-272558

Q13315

Q4G0J3

1

phosphorylation

down-regulates quantity by destabilization

0.2

Altogether, the results suggest that ATM-mediated T440 phosphorylation enhances LARP7-BARD1 interaction and facilitates BRCA1/BARD1-mediated LARP7 ubiquitination and degradation.

SIGNOR-275580

P17252

P04049

1

phosphorylation

down-regulates

0.558

Pka can inhibit raf-1 function directly via phosphorylation of the raf-1 kinase domain

SIGNOR-34761

P61224

P17612

0

phosphorylation

up-regulates

0.522

These results provide a mechanistic explanation for the differential effects of rap1 phosphorylation by pka on effector protein interaction. camp is one among several pathways leading to rap1 activation

SIGNOR-187410

P22459

Q8TBB1

0

ubiquitination

down-regulates quantity by destabilization

0.283

We used the Ligand of Numb protein X (LNX) family of E3s, a group of PDZ domain-containing RING-type E3 ubiquitin ligases, to demonstrate the feasibility of this strategy. Many potential substrates of LNX E3s were identified. Eight of the nine selected candidates were ubiquitinated in vitro, and two novel endogenous substrates, PDZ-binding kinase (PBK) and breakpoint cluster region protein (BCR), were confirmed in vivo.The C-terminal LNX1 PDZ1-binding motifs of the ATP-binding cassette, subfamily A member 1 (ABC-1), PBK, glutamate receptor, ionotropic, N-methyl d-aspartate 1 (GRIN1), and Claudin-17 significantly promoted the ubiquitination of the corresponding artificial degrons by LNX1ΔPDZ234.

SIGNOR-272899

P01106

Q13627

0

phosphorylation

down-regulates quantity

0.374

We also found that DYRK1A phosphorylated c-Myc on Ser62, priming phosphorylation on Thr58 by GSK3\u03b2 and subsequent degradation.|c-Myc expression is down-regulated by DYRK1A.

SIGNOR-279609

Q92574

P54646

0

phosphorylation

up-regulates

0.551

Under energy starvation conditions, the amp-activated protein kinase (ampk) phosphorylates tsc2 and enhances its activity.

SIGNOR-119541

P16519

P01189-PRO_0000024969

1

cleavage

up-regulates quantity

0.2

POMC is post-translationally cleaved by prohormone convertase enzymes 1 and 2 (PC1, PC2) into ACTH, an N-terminal glycopeptide

SIGNOR-268725

O60341

Q16695

1

demethylation

up-regulates activity

0.2

Here, we provide evidence that LSD1 (KIAA0601), a nuclear homolog of amine oxidases, functions as a histone demethylase and transcriptional corepressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription.

SIGNOR-264508

Q04206

O14920

0

phosphorylation

up-regulates activity

0.886

Rela is phosphorylated at ser536 by ikkbeta, ikkalfa, ikkepsilon, nf-kb activating kinase (nak, also known as tank-binding kinase-1 tbk1) and rsk1 (also known as p90 ribosomal protein s6 kinase (p90s6k). We now present evidence that suggests that the upstream kinase ikkbeta plays an important role in tax-induced p53 inhibition through phosphorylation of p65/rela at ser-536. Ikkbeta plays an important role in tax-induced p53 inhibition through phosphorylation of p65/rela at ser-536.

SIGNOR-138903

Q05513

P52565

1

phosphorylation

up-regulates activity

0.246

Hence, it may be reasonable to deduce that N-formyl-methionyl-leucyl-phenylalanine binds its receptors to activate protein kinase C\u03b6 to generate superoxide, which in turn stimulates the motility in an autocrine manner via the protein kinase C\u03b6-RhoGDI-1-RhoGTPase pathway.|In these cells, protein kinase C zeta was activated to phosphorylate RhoGDI-1, which liberated RhoGTPases, leading to their activation.

SIGNOR-280089