GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q15418	Q16821	1	phosphorylation	up-regulates activity	0.43	The protein G(M), which targets protein phosphatase 1 (PP1) to the glycogen particles and sarcoplasmic reticulum (SR) of striated muscles, is known to be phosphorylated at Ser48 and Ser67 in vitro by adenosine 3',5' cyclic monophosphate-dependent protein kinase (PKA) and at Ser48 by MAP kinase-activated protein kinase-1 (MAPKAP-K1, also called p90 RSK). The phosphorylation of Ser48 increases the rate at which the glycogen-associated PP1.G(M) complex dephosphorylates (activates) glycogen synthase, but the phosphorylation of Ser67 has the opposite effect, suppressing the activity of PP1 toward glycogen-bound substrates.	SIGNOR-249036
P49840	P10636	1	phosphorylation	down-regulates	0.429	Tau is phosphorylated by gsk-3 at several sites found in alzheimer disease and its biological activity markedly inhibited only after it is prephosphorylated by a-kinase.	SIGNOR-60651
P24941	P38432	1	phosphorylation	up-regulates	0.381	In particular, we have recently found that the cdk2/cyclin e complex can phosphorylate coilin in vitro . there is but a single consensus cdk2/cyclin e phosphorylation site in coilin, located at serine 184. when serine 184 was mutated to an alanine (s184a), mimicking a dephosphorylated state, a nucleolar mislocalization similar to that of gfp-coilin(1_248) was observed	SIGNOR-84949
Q9Y297	Q13485	1	ubiquitination	down-regulates	0.388	Here we show that beta-trcp1, a f-box protein in the scf e3 ligase complex, interacts with smad4 and induces the degradation of smad4	SIGNOR-123057
P22736	P31749	0	phosphorylation	down-regulates activity	0.729	We show that akt interacts with nur77 and inactivates nur77 by phosphorylation at ser-350	SIGNOR-252466
Q8NHY2	Q13315	0	phosphorylation	down-regulates	0.2	Atm engages autodegradation of the e3 ubiquitin ligase cop1 after dna damage. We observed that in response to dna damage, atm phosphorylated cop1 on ser(387) and stimulated a rapid autodegradation mechanism	SIGNOR-149082
P10912	P23467	0	dephosphorylation	down-regulates	0.295	Inally, mrna tissue distribution of these ptps by rt-pcr analysis and coexpression of the wild-type ptps to test their ability to dephosphorylate ligand-activated ghr suggest ptp-h1 and ptp1b as potential candidates involved in ghr signaling.	SIGNOR-104580
Q9Y3L3	P63000	1	gtpase-activating protein	down-regulates activity	0.38	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-260514
P42345	Q9H063	1	phosphorylation	down-regulates	0.712	The protein is phosphorylated mainly on residues s60, s68, and s75, and this inhibits its pol iii repression function. The responsible kinase is mtorc1, which phosphorylates maf1 directly.	SIGNOR-165795
Q9UHC7	P46783	1	ubiquitination	up-regulates activity	0.2	We show that MKRN1 directly binds to the cytoplasmic poly(A)-binding protein (PABPC1) and associates with polysomes. MKRN1 is positioned upstream of poly(A) tails in mRNAs in a PABPC1-dependent manner. Ubiquitin remnant profiling and in vitro ubiquitylation assays uncover PABPC1 and ribosomal protein RPS10 as direct ubiquitylation substrates of MKRN1.Our data show that MKRN1 associates with polysomes and ubiquitylates RPS10, indicating a role in translational control. We hypothesize that ribosomes encountering the MKRN1-PABPC1 complex are stalled, possibly via ubiquitylation of RPS10 on K107 and other MKRN1 substrates.	SIGNOR-272216
P04062	P19484	0	transcriptional regulation	up-regulates quantity by expression	0.325	Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy\|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1\|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants	SIGNOR-276551
P42574	Q14790	0	cleavage	up-regulates activity	0.726	Triggering of the DISC leads to caspase-8 activation. Active caspase-8 cleaves caspase-3 which, in type I cells, leads to cell death induction.	SIGNOR-171767
Q8IWU2	P62136	1	phosphorylation	down-regulates activity	0.57	Kpi-2 kinase domain phosphorylated protein phosphatase-1 (pp1c) at thr(320), which attenuated pp1c activity.	SIGNOR-94631
P49137	P16220	1	phosphorylation	up-regulates activity	0.691	Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2.	SIGNOR-166619
P17612	O15554	1	phosphorylation	down-regulates activity	0.2	Mutating the single PKA site (S334A) in human KCa3.1 abolished the PKA-dependent regulation. CaM-affinity chromatography showed that CaM binding to KCa3.1 was decreased by PKA-dependent phosphorylation of S334, and this regulation was absent in the S334A mutant.The results above indicate that PKA activation led to a phosphorylation event that inhibited KCa3.1 channel activity	SIGNOR-276855
P25116	Q15831	0	phosphorylation	up-regulates activity	0.2	LKB1 phosphorylates PAR-1 at the T408 site xref .\|LKB1 thus positively regulates PAR-1 at the postsynapse.	SIGNOR-278992
Q13224	P12931	0	phosphorylation	up-regulates activity	0.559	We have investigated the tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B by exogenous Src Phosphorylation-site specific antibodies identified NR2B Tyr1472 as a phosphorylation site for intrinsic PSD tyrosine kinases	SIGNOR-247180
Q9HAW4	O00311	0	phosphorylation	up-regulates activity	0.742	Cdc7 phosphorylates Claspin in a manner dependent on AP and inhibits N\u2013C interaction.\|Thus, Cdc7-ASK may activate DNA and PCNA bindings of Claspin through AP-mediated phosphorylation.	SIGNOR-279360
Q13882	P60484	0	dephosphorylation	down-regulates activity	0.416	PTEN inhibits PTK6 activity and downstream signaling in prostate cancer cells.\|Using an in vitro phosphatase assay, we observed that PTEN was able to dephosphorylate PTK6 at tyrosine residue 342 in a dose dependent manner.	SIGNOR-276975
P28482	P23443	1	phosphorylation	up-regulates	0.596	Erk phosphorylates multiple cytoplasmatic and cytoskeletal proteins, including mapk-activated protein kinases and the ribosomal p70-s6 kinase	SIGNOR-28800
P15311	P00533	0	phosphorylation	up-regulates	0.529	Ezrin was initially identified as a substrate for tyrosine phosphorylation by egfr (bretscher, 1989) and phosphorylation of residues y145 and y353 were detected to high stoichiometry after egf treatment . Phosphorylation of ezrin at y353 has been delineated to signal survival during epithelial cell differentiation via the phosphatidylinositol 3-kinase (pi3k)/akt pathway.	SIGNOR-133215
P16949	Q13153	0	phosphorylation	down-regulates	0.374	The hgf-induced wave2 transport, lamellipodia formation, stathmin/op18 phosphorylation at ser38 and binding to kinesin-wave2 complex, but not stathmin/op18 phosphorylation at ser25 and microtubule growth, were abrogated by pak1 inhibitor ipa-3	SIGNOR-183503
Q07812	P31749	0	phosphorylation	down-regulates activity	0.486	Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophilsWe suggest that Bax is regulated by phosphorylation of Ser(184) in an Akt-dependent manner and that phosphorylation inhibits Bax effects on the mitochondria by maintaining the protein in the cytoplasm, heterodimerized with antiapoptotic Bcl-2 family members	SIGNOR-252538
Q13131	Q8WUI4	1	phosphorylation	down-regulates	0.273	Another recently described set of transcriptional regulators targeted by ampk and its related family members across a range of eukaryotes are the class iia family of histone deacetylases (hdacs).	SIGNOR-176491
Q92696	P20339	1	lipidation	up-regulates activity	0.625	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-265572
Q9H093	Q15831	0	phosphorylation	up-regulates	0.273	A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold.	SIGNOR-122717
Q13191	P42226	1	ubiquitination	down-regulates quantity	0.2	Having shown that Cbl-b negatively regulates Stat6, we further investigated the mechanism of this regulation by determining whether Cbl-b associates with Stat6.\|Our data demonstrate that Stat6 is ubiquitinated at K108 and K398 by Cbl-b, and that Stat6 ubiquitination is a critical post-translational regulatory mechanism for Stat6.	SIGNOR-278806
Q13547	Q00987	0	ubiquitination	down-regulates quantity by destabilization	0.468	MDM2 induces ubiquitination of HDAC1 in VSMCs.\|Under calcification inducing conditions, proteasomal degradation of HDAC1 precedes VC and it is mediated by MDM2 E3 ubiquitin ligase that initiates HDAC1 K74 ubiquitination.	SIGNOR-278761
P27987	P17612	0	phosphorylation	down-regulates activity	0.351	Two isoforms of the inositol 1,4,5-trisphosphate 3-kinase have been identified, the A form and the B form. phosphorylation of isoform A by the cyclic AMP-dependent protein kinase increased activity 1.5-fold, whereas phosphorylation of isoform B decreased activity by 45%. major phosphorylation sites in the protein are Ser119 for PKA. Ser119 in the A isoform is conserved in the B isoform as Ser328	SIGNOR-249995
Q6UB99	Q16620	1	transcriptional regulation	up-regulates quantity by expression	0.2	Ankrd11 knockdown decreases the levels of bdnf and Trkb mRNAs. Next, we examine whether ANKRD11 accesses the Trkb promoter in cortical neurons. We performed the chromatin immunoprecipitation assay (ChIP) using an ANKRD11 antibody followed by PCR to amplify the Trkb promoter region. We found that ANKRD11 binds to the Trkb promoter (Fig. 6E). As expected, the level of ANKRD11 binding was decreased in the Ankrd11 knockdown condition.	SIGNOR-266731
P07948	P20273	1	phosphorylation	down-regulates activity	0.743	LYN is a BCR-associated SRC kinase involved in the positive regulation of BCR, but it also functions as a negative regulator by phosphorylating the immunoreceptor tyrosine-based inhibitory motifs (ITIMs) of CD22.	SIGNOR-268443
O60674	P02647	1	null	up-regulates activity	0.298	ApoA-I interactions with ABCA1 and lipid efflux to apoA-I were substantially impaired by inhibiting or abolishing JAK2, whereas ABCA1 protein levels were unaffected, and ABCA1 cholesterol translocase activity was only slightly reduced. The most likely explanation for these findings is that JAK2 promotes apolipoprotein interactions with ABCA1 or a closely proximal site, and this facilitates the removal of cellular lipids. the interaction of apolipoproteins with ABCA1-expressing cells activates JAK2, which in turn activates a process that enhances apolipoprotein interactions with ABCA1 and lipid removal from cells	SIGNOR-252107
Q14653	P05231	1	transcriptional regulation	up-regulates quantity by expression	0.406	Recent reports show that in mice the microbiome, comprising commensal microorganisms that colonize body surfaces, promotes a partial and low-grade M1-like phenotype in macrophages throughout the body, including those in lymphoid organs (119, 120). This M1-like priming of macrophages induces chromatin remodeling with increased H3K4me3 marks at Ifnb, Il6, and Tnf promoters, which is associated with increased binding of NF-κB p65, IRF3, and Pol II upon cell stimulation	SIGNOR-251721
P28482	Q96LC9	1	phosphorylation	up-regulates	0.253	Phosphomimetic mutation of this site (s74d) moderately enhanced bmf apoptotic activity in vivo.22 here, we demonstrate a previously unrecognized mode of regulation of bmf. We show that b-raf-mek-erk2 signaling regulates bmf phosphorylation at serine 74 and serine 77. Phosphorylation of serine 77 downregulates the pro-apoptotic activity of bmf.	SIGNOR-195475
Q5T0T0	P01903	1	polyubiquitination	down-regulates quantity by destabilization	0.2	Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination.	SIGNOR-271411
P45974	P0CG48	1	cleavage	up-regulates quantity	0.847	Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.	SIGNOR-270822
P23508	Q13535	0	phosphorylation	up-regulates activity	0.2	MCC is phosphorylated at the ATM/ATR consensus sites Ser118 and Ser120. Finally, mutation of S118/120 to alanine did not affect MCC nuclear shuttling following UV but did impair MCC G2/M checkpoint activity.	SIGNOR-273514
Q96J02	Q9UBN4	1	ubiquitination	down-regulates activity	0.35	Ubiquitination of TRPV4 is dramatically increased by the HECT (homologous to E6-AP carboxyl terminus)-family ubiquitin ligase AIP4 without inducing degradation of this channel. Instead, AIP4 promotes the endocytosis of TRPV4 and decreases its amount at the plasma membrane.	SIGNOR-272624
P51452	P04626	1	dephosphorylation	down-regulates activity	0.268	Expression of VHR inhibited the activation of phospholipase Cγ and protein kinase C, both downstream effectors of Tyr-992 phosphorylation of EGFR. \| We found that VHR decreased ErbB2 phosphorylation in vitro and in a cellular context, and the dephosphorylation of ErbB2 was more evident at Tyr-877 and Tyr-1221 than those at Tyr-1139 and Tyr-1248 (supplemental Fig. S1). Our data indicated that VHR was a cellular PTP against EGFR and ErbB2.	SIGNOR-248533
Q01130	Q92993	0	acetylation	down-regulates	0.466	In this study, we provide the first evidence that the acetyltransferase tip60 acetylates srsf2 on its lysine 52 residue inside the rna recognition motif, and promotes its proteasomal degradation.	SIGNOR-170594
O15354	O60260	0	ubiquitination	down-regulates quantity by destabilization	0.2	Parkin is a protein of 465 amino acids, and its structure includes a ubiquitin homologous domain in its N terminus and two RING finger domains in its C terminus. Molecular studies have determined that parkin is an E3 ubiquitin ligase function, implicating parkin in the ubiquitin-proteasome system, and raising the possibility that mutations in the gene lead to loss or diminished function. Three substrates for the ubiquitin-ligase function of parkin have been identified to date.1. A 22kDa glycosolated form of alpha-synuclei\|2. Parkin-associated endothelin receptor-like receptor (Pael-R).	SIGNOR-249706
P54764	O00712	0	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268901
O00429	P49841	0	phosphorylation	up-regulates activity	0.388	We identified glycogen synthase kinase (GSK)3β-dependent Drp1 phosphorylation at Ser(40) and Ser(44), which increases Drp1 GTPase activity and its mitochondrial distribution and could induce mitochondrial fragmentation.	SIGNOR-276849
Q13535	Q8WXE1	1	phosphorylation	up-regulates	0.878	When dna is damaged, the atr-atrip complex is recruited to chromatin and is activated to transduce the checkpoint signal, but the precise kinase activation mechanism remains unknown. Here, we show that atrip is phosphorylated in an atr-dependent manner after genotoxic stimuli. The serine 68 and 72 residues are important for the phosphorylation in vivo and are required exclusively for direct modification by atr in vitro.	SIGNOR-129473
Q9NR48	Q9ULB1	1	transcriptional regulation	down-regulates quantity by repression	0.259	Our results reveal that a novel process of activity-dependent transcriptional repression exists in neurons and that Ash1L mediates the long-term repression of nrxn1α, thus implicating an important role for epigenetic modification in brain functioning.	SIGNOR-269056
O95865	Q9UHD2	0	phosphorylation	down-regulates activity	0.2	TANK-binding kinase 1 (TBK1), a kinase downstream of MAVS, inhibited DDAH2 by phosphorylating DDAH2 at multiple sites. \|The T203D, T211D, S245D, and S253D mutations significantly reduced the inhibitory effect of DDAH2 on RLR signaling, suggesting that phosphorylation of these residues was critical for DDAH2 to inhibit activation o	SIGNOR-275648
Q9UQB9	P68431	1	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
P13612	P17612	0	phosphorylation	up-regulates activity	0.494	PKA phosphorylationin vitro blocks the binding of the alpha4 tail to paxillin. A mutation that mimics alpha4 phosphorylation disrupts paxillin binding and promotes cell spreading	SIGNOR-110119
P16104	Q13535	0	phosphorylation	up-regulates activity	0.2	ATR and ATM also phosphorylate histone H2AX at Ser 139 (gammaH2AX) in response to DNA double-strand breaks (DSBs), which spreads along the DNA up to 200-400 kb and helps in the recruitment of proteins involved in DNA damage repair and checkpoint activation .	SIGNOR-279356
Q05655	P19429	1	phosphorylation	up-regulates activity	0.272	Src phosphorylates pkcdelta at tyr311 and tyr332 leading to enhanced pkcdelta autophosphorylation at thr505 (its activation loop) and pkcdelta-dependent ctni phosphorylation at both ser23/ser24 and thr144.	SIGNOR-178880
P31749	P29474	1	phosphorylation	up-regulates	0.877	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 a on serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no.	SIGNOR-112363
P24941	Q96EB6	1	phosphorylation	up-regulates activity	0.465	Sirt1 is in turn phosphorylated by Cdk2, which may further regulate its activity.\|Taken together, these data demonstrate that Cdk2 deletion does not decrease Hif1\u03b1 expression induced by HX, and strongly suggests that the phosphorylation of Sirt1 at Ser47 by Cdk2 requires Sirt1 deacetylase activity.	SIGNOR-279513
Q66PJ3	Q96BR1	0	phosphorylation	down-regulates activity	0.2	AIP4 is phosphorylated by CISK in vitro on WW domain residues, which may impact its ability to interact with and ubiquitinate substrate proteins.\|Expression of a constitutively active CISK inhibits CXCR4 degradation, possibly by attenuating CXCR4 binding to and ubiquitination by AIP4 and/or modulating the action of AIP4 on a protein involved in CXCR4 endosomal sorting .	SIGNOR-280124
Q13043	Q9Y243	0	phosphorylation	down-regulates	0.261	Full activation of mst1 requires an activation cleavage that is prevented by the phosphorylation of thr-387 by akt.	SIGNOR-201129
Q8IXW5	P24928	1	dephosphorylation	up-regulates activity	0.738	In addition, we show that RPAP2 is a CTD Ser5 phosphatase. Taken together, our results indicate that during transcription of snRNA genes, Ser7 phosphorylation facilitates recruitment of RPAP2, which in turn both recruits Integrator and dephosphorylates Ser5.\|The Pol II CTD is first phosphorylated on Ser5 and then on Ser7 by CDK7. RPAP2 associates with the Pol II CTD after Ser7 phosphorylation and tethers a subcomplex of Integrator to snRNA genes. RPAP2 dephosphorylates Ser5P of the CTD, facilitating transcription and the subsequent recruitment of the Int11 catalytic subunit of Integrator	SIGNOR-248748
O15164	P04637	1	ubiquitination	down-regulates	0.532	New ring-domain e3-ubiquitin ligase trim24 that targets p53 for degradation	SIGNOR-188726
P32243	P14651	0	transcriptional regulation	up-regulates quantity by expression	0.2	Transactivation of the mouse OTX2 Luc constructs by the human HOXB1, HOXB2, and HOXB3 proteins. \| Likewise, the construct pOTX2LucΔ−710 showed an 8-, 12-, and 6-fold increase in transcriptional activity if co-transfected with pSG-HOXB1, -HOXB2, and -HOXB3, respectively	SIGNOR-261635
P27695	Q92911	1	transcriptional regulation	up-regulates quantity by expression	0.2	These data demonstrate a role for APE/Ref-1 protein in the transcriptional regulation of NIS gene expression by itself and in cooperation with PAX8.	SIGNOR-261564
P67775	P23443	1	dephosphorylation	down-regulates	0.72	Protein phosphatase 2a inactivates the mitogen-stimulated s6 kinase from swiss mouse 3t3 cells	SIGNOR-23575
Q05397	Q9UQM7	0	phosphorylation	up-regulates	0.272	Furthermore, activated camkii directly phosphorylated the recombinant cooh-terminal region of fak at a residue equivalent to ser-843.	SIGNOR-135631
P23470	O60496	1	dephosphorylation	up-regulates activity	0.2	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254698
Q14493	Q99877	1	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-265392
Q13322	P12931	0	phosphorylation	down-regulates	0.447	Grb10 tyrosine phosphorylation was stimulated by expression of constitutively active src or fyn in cells and by incubation with purified src or fyn in vitro. The insulin stimulated or src/fyn-mediated tyrosine phosphorylation in vivo was significantly reduced when grb10 tyrosine 67 was changed to glycine. This mutant form of grb10 bound with higher affinity to the ir in cells than that of the wild-type protein, suggesting that tyrosine phosphorylation of grb10 may normally negatively regulate its binding to the ir.	SIGNOR-78706
P13569	Q99942	0	ubiquitination	down-regulates quantity by destabilization	0.665	JB12 cooperates with cytosolic Hsc70 and the ubiquitin ligase RMA1 to target CFTR and CFTRΔF508 for degradation.	SIGNOR-271494
O43561	P27361	0	phosphorylation	down-regulates	0.304	Lat, an adapter protein essential for t-cell signaling, is phosphorylated at its thr 155 by erk in response to t-cell receptor stimulation. Thr 155 phosphorylation reduces the ability of lat to recruit plcgamma1 and slp76, leading to attenuation of subsequent downstream events such as [ca2+]i mobilization and activation of the erk pathway.	SIGNOR-125770
Q149N8	P12004	1	ubiquitination	up-regulates	0.553	We provide evidence that similar to rad5, shprh physically interacts with the human rad6rad18 and mms2ubc13 protein complexes, and importantly, we show that it exhibits an ubiquitin ligase activity and mediates mms2ubc13-dependent polyubiquitylation of pcna. Thus, shprh is a functional homolog of rad5.	SIGNOR-187757
Q13618	Q03933	1	ubiquitination	down-regulates quantity by destabilization	0.326	Here we show that the PEST sequences of a short-lived protein called HSF2 interact with Cullin3, a subunit of a Cullin-RING E3 ubiquitin ligase, and that this interaction mediates the Cul3-dependent ubiquitination and degradation of HSF2	SIGNOR-239129
Q9H165	P69891	1	transcriptional regulation	down-regulates quantity by repression	0.446	Our findings reveal that direct γ-globin gene promoter repression by BCL11A underlies hemoglobin switching.	SIGNOR-269067
Q99717	O95257	1	transcriptional regulation	up-regulates quantity	0.2	Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation	SIGNOR-268942
O43315	Q05513	0	phosphorylation	up-regulates	0.2	Wt-pkc_-mediated phosphorylation of wt aqp9 in vitro. In the experiments, substitution of ser11 to ala markedly inhibited phosphorylation. the s11a mutation in fibroblasts caused a smoother cell periphery with fewer aqp9-induced filopodia	SIGNOR-176278
P03372	P11511	1	transcriptional regulation	down-regulates quantity by repression	0.516	By binding to S1, ERalpha down-regulates the aromatase promoter activity.	SIGNOR-271683
P48729	Q12968	1	phosphorylation	down-regulates activity	0.59	Dominant-negative cki alpha Induces nuclear import of nf-at4 these results demonstrated that the cki alpha Phosphorylation sites identified in vitro were also specifically phosphorylated by cki alpha In vivo, and that these residues were crucial for the masking of the nls of nf-at4.	SIGNOR-109781
P06239	Q9NRW4	0	dephosphorylation	down-regulates activity	0.273	Because JKAP dephosphorylates and inactivates Lck in T cells [ xref ], we studied whether JKAP downregulation results in Lck activation in SLE T cells.	SIGNOR-277148
P10636	P43405	0	phosphorylation	down-regulates	0.466	We established that tyrosine 18 was the primary residue in tau phosphorylated by sykphosphorylation of tau by syk could be involved in neurite outgrowth.	SIGNOR-159648
Q9UGL1	P78317	0	sumoylation	down-regulates quantity by destabilization	0.3	Hendriks and coworkers showed that, in response to alkylation damage by methyl methanesulfonate (MMS), SUMOylated JARID1B (KDM5B) is ubiquitylated by the SUMOtargeted ubiquitin ligase RNF4 and degraded by the proteasome, whereas JARID1C (KDM5C) is SUMOylated and recruited to the chromatin to demethylate histone H3K4 (Hendriks et al., 2015).	SIGNOR-271575
P62979	Q93008	0	cleavage	up-regulates quantity	0.504	Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.	SIGNOR-270826
P51608	O15111	0	phosphorylation	up-regulates activity	0.2	Representative confocal micrographs of 4th day differentiating cultures are shown. (C) IKK\u03b1 promotes MeCP2-dependent BDNF expression.\|The characterization of IKK\u03b1-mediated phosphorylation of MeCP2 at Ser421 and other residues and their effects on the activity of MeCP2 is a topic of current work in our laboratory.	SIGNOR-279459
P35558	Q8IXJ6	0	deacetylation	up-regulates quantity by stabilization	0.426	Conversely, SIRT2 deacetylates and stabilizes PEPCK1.\|Furthermore, coexpression of P300 increased acetylation levels of wild-type PEPCK1, but not PEPCK13K/R, indicating that P300 acts on these lysine residues of PEPCK1	SIGNOR-267599
P31749	Q07352	1	phosphorylation	down-regulates	0.657	Here we report that protein kinase b (pkb/akt) stabilizes are transcripts by phosphorylating brf1 at serine 92 (s92). Recombinant brf1 promoted in vitro decay of are-containing mrna (are-mrna), yet phosphorylation by pkb impaired this activity.	SIGNOR-130376
P12931	P30411	1	phosphorylation	up-regulates	0.262	Here we demonstrate that egf is capable of inducing src-mediated phosphorylation of the tyrosine residues 177 and 347 of bkr. Their replacement by phenylalanine led to bkr mutants which are unable to activate the camp pathway.	SIGNOR-141103
Q12955	Q6ZMI3	0	relocalization	up-regulates quantity	0.41	Ankyrin-G is recruited to the nodes of Ranvier by gliomedin, which is produced by Schwann cells and accumulates in the perinodal extracellular matrix. As a ligand for neurofascin-186, gliomedin causes the nodal clustering of this cell adhesion molecule, which in turn recruits to the nodal plasma membrane an ankyrin-G protein network consisting of voltage-gated sodium or potassium channels (KCNQ2/3) and β4-spectrin.	SIGNOR-266725
P42224	Q07912	0	phosphorylation	up-regulates activity	0.357	Hence, ACK1 activates STAT1 through its kinase activity.\|We found that wild-type ACK1 and to a larger extent constitutively active ACK1 increased the phosphorylation of cytoplasmic STAT1 at Y701.	SIGNOR-278348
Q16666	P68400	0	phosphorylation	up-regulates activity	0.321	Here we examine the functionality of the interferon-induced factor 16 (IFI 16) CcN motif, demonstrating its ability to target a heterologous protein to the nucleus, and to be phosphorylated specifically by the CcN-motif-phosphorylating protein kinase CK2 (CK2). \| Specific phosphorylation of IFI 16 Ser132 in HeLa cell extracts and by purified CK2 in vitro	SIGNOR-250902
P53350	Q9NYZ3	1	phosphorylation	up-regulates	0.736	In this study, we show that g2 and s-phase-expressed 1 (gtse1) protein, a negative regulator of p53, is required for g2 checkpoint recovery and that plk1 phosphorylation of gtse1 at ser 435 promotes its nuclear localization, and thus shuttles p53 out of the nucleus to lead to its degradation during the recovery.	SIGNOR-166417
P46527	P28482	0	phosphorylation	up-regulates	0.346	Phosphorylation on ser-10 of kip1 is the major site of phosphorylation in resting cells, takes place at the g(0)-g1 phase and leads to protein stability.	SIGNOR-77651
P25054	P49841	0	phosphorylation	up-regulates	0.758	Gsk-3beta-dependent phosphorylation of apc.	SIGNOR-75366
O75030	P16220	0	transcriptional regulation	up-regulates quantity by expression	0.633	Therefore, the molecular steps linking cAMPto melanogenesis up-regulation appear currently better elucidated. cAMP activates PKA, and PKA phosphorylates and activates CREB which, when activated, binds to the CRE domain present in the microphthalmia promoter,thereby up-regulating its transcription.	SIGNOR-249619
Q08209	O95644	1	dephosphorylation	up-regulates	0.825	Calcineurin directly dephosphorylates nfat resulting in the nuclear import of nfat.	SIGNOR-176370
P05771	P41594	1	phosphorylation	up-regulates activity	0.354	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-249286
Q9NX09	O60260	0	ubiquitination	down-regulates quantity by destabilization	0.2	In conclusion, our work in cellular and animal models and in human samples strongly indicates that RTP801 is a substrate of parkin and that RTP801 elevation due to parkin loss of function in both AR-JP and sporadic Parkinson's disease may contribute to neurodegeneration.\|We showed that parkin poly-ubiquitinates RTP801, both in vitro and in vivo.	SIGNOR-278560
P31270	P01236	1	transcriptional regulation	up-regulates quantity by expression	0.351	HoxA-11 enhanced upregulation of PRL only in differentiated cells.	SIGNOR-261630
Q14493	P0C5Z0	1	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
Q9UPN4	P49137	0	phosphorylation	down-regulates quantity	0.291	We identify CEP131 as a major Centriolar satellites-associated substrate of p38-dependent, MK2-mediated phosphorylation on two defined residues and show that these modifications promote binding to 14-3-3 proteins, in turn leading to cytoplasmic sequestration of CEP131 and associated Centriolar satellites factors.\|We therefore conclude that MK2 dependent phosphorylation of CEP131 at S47 and S78 and the ensuing binding of 14-3-3 proteins play an essential role in triggering stress induced remodelling of CS.	SIGNOR-278181
Q06330	Q16539	0	phosphorylation	down-regulates quantity by destabilization	0.247	P38 MAPK phosphorylates RBP-Jk at Thr339 by physical binding, which subsequently induces the degradation and ubiquitylation of the RBP-Jk protein.	SIGNOR-276403
Q9UKT6	P49841	0	phosphorylation	up-regulates activity	0.2	GSK-3beta phosphorylates FBXL21 and TCAP to activate FBXL21-mediated, phosphodegron-dependent TCAP degradation.\|These results show direct GSK-3beta phosphorylation of TCAP S157 and FBXL21 T33 sites.	SIGNOR-264851
Q96RR4	P49840	0	phosphorylation	down-regulates	0.269	Cdk5 and gsk3 phosphorylate ser-129, ser-133, and ser-137. Mutation of ser-129, ser-133, and ser-137 increases autonomous activity with little change in ca2 /cam-dependent activity.	SIGNOR-198122
P04629	Q9BV47	0	dephosphorylation	down-regulates activity	0.371	NEAP and DUSP26 dephosphorylated TrkA and FGFR1 directly.\|We found that NEAP, but not its phosphatase-defective mutant, suppressed nerve growth factor (NGF) receptor TrkA and fibroblast growth factor receptor 1 (FGFR1) activation in PC12 cells	SIGNOR-277105
P52333	O95644	1	phosphorylation	up-regulates activity	0.383	Here we found that IL-7-Jak3 signals activated the transcription factor NFATc1 in DN thymocytes by phosphorylating Tyr371 in the regulatory region of NFATc1.	SIGNOR-276435
P61006	Q5S007	0	phosphorylation	up-regulates activity	0.33	In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. \|Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.\|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease	SIGNOR-260267
P78536	P15941	1	cleavage	down-regulates	0.308	These characteristics along with studies conducted with cell lines genetically deficient in various adams (for a disintegrin and metalloprotease) identified tumor necrosis factor-alpha converting enzyme (tace)/adam 17 as a muc1 sheddase.	SIGNOR-95630

Q15418

Q16821

1

phosphorylation

up-regulates activity

0.43

The protein G(M), which targets protein phosphatase 1 (PP1) to the glycogen particles and sarcoplasmic reticulum (SR) of striated muscles, is known to be phosphorylated at Ser48 and Ser67 in vitro by adenosine 3',5' cyclic monophosphate-dependent protein kinase (PKA) and at Ser48 by MAP kinase-activated protein kinase-1 (MAPKAP-K1, also called p90 RSK). The phosphorylation of Ser48 increases the rate at which the glycogen-associated PP1.G(M) complex dephosphorylates (activates) glycogen synthase, but the phosphorylation of Ser67 has the opposite effect, suppressing the activity of PP1 toward glycogen-bound substrates.

SIGNOR-249036

P49840

P10636

1

phosphorylation

down-regulates

0.429

Tau is phosphorylated by gsk-3 at several sites found in alzheimer disease and its biological activity markedly inhibited only after it is prephosphorylated by a-kinase.

SIGNOR-60651

P24941

P38432

1

phosphorylation

up-regulates

0.381

In particular, we have recently found that the cdk2/cyclin e complex can phosphorylate coilin in vitro . there is but a single consensus cdk2/cyclin e phosphorylation site in coilin, located at serine 184. when serine 184 was mutated to an alanine (s184a), mimicking a dephosphorylated state, a nucleolar mislocalization similar to that of gfp-coilin(1_248) was observed

SIGNOR-84949

Q9Y297

Q13485

1

ubiquitination

down-regulates

0.388

Here we show that beta-trcp1, a f-box protein in the scf e3 ligase complex, interacts with smad4 and induces the degradation of smad4

SIGNOR-123057

P22736

P31749

0

phosphorylation

down-regulates activity

0.729

We show that akt interacts with nur77 and inactivates nur77 by phosphorylation at ser-350

SIGNOR-252466

Q8NHY2

Q13315

0

phosphorylation

down-regulates

0.2

Atm engages autodegradation of the e3 ubiquitin ligase cop1 after dna damage. We observed that in response to dna damage, atm phosphorylated cop1 on ser(387) and stimulated a rapid autodegradation mechanism

SIGNOR-149082

P10912

P23467

0

dephosphorylation

down-regulates

0.295

Inally, mrna tissue distribution of these ptps by rt-pcr analysis and coexpression of the wild-type ptps to test their ability to dephosphorylate ligand-activated ghr suggest ptp-h1 and ptp1b as potential candidates involved in ghr signaling.

SIGNOR-104580

Q9Y3L3

P63000

1

gtpase-activating protein

down-regulates activity

0.38

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-260514

P42345

Q9H063

1

phosphorylation

down-regulates

0.712

The protein is phosphorylated mainly on residues s60, s68, and s75, and this inhibits its pol iii repression function. The responsible kinase is mtorc1, which phosphorylates maf1 directly.

SIGNOR-165795

Q9UHC7

P46783

1

ubiquitination

up-regulates activity

0.2

We show that MKRN1 directly binds to the cytoplasmic poly(A)-binding protein (PABPC1) and associates with polysomes. MKRN1 is positioned upstream of poly(A) tails in mRNAs in a PABPC1-dependent manner. Ubiquitin remnant profiling and in vitro ubiquitylation assays uncover PABPC1 and ribosomal protein RPS10 as direct ubiquitylation substrates of MKRN1.Our data show that MKRN1 associates with polysomes and ubiquitylates RPS10, indicating a role in translational control. We hypothesize that ribosomes encountering the MKRN1-PABPC1 complex are stalled, possibly via ubiquitylation of RPS10 on K107 and other MKRN1 substrates.

SIGNOR-272216

P04062

P19484

0

transcriptional regulation

up-regulates quantity by expression

0.325

Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants

SIGNOR-276551

P42574

Q14790

0

cleavage

up-regulates activity

0.726

Triggering of the DISC leads to caspase-8 activation. Active caspase-8 cleaves caspase-3 which, in type I cells, leads to cell death induction.

SIGNOR-171767

Q8IWU2

P62136

1

phosphorylation

down-regulates activity

0.57

Kpi-2 kinase domain phosphorylated protein phosphatase-1 (pp1c) at thr(320), which attenuated pp1c activity.

SIGNOR-94631

P49137

P16220

1

phosphorylation

up-regulates activity

0.691

Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2.

SIGNOR-166619

P17612

O15554

1

phosphorylation

down-regulates activity

0.2

Mutating the single PKA site (S334A) in human KCa3.1 abolished the PKA-dependent regulation. CaM-affinity chromatography showed that CaM binding to KCa3.1 was decreased by PKA-dependent phosphorylation of S334, and this regulation was absent in the S334A mutant.The results above indicate that PKA activation led to a phosphorylation event that inhibited KCa3.1 channel activity

SIGNOR-276855

P25116

Q15831

0

phosphorylation

up-regulates activity

0.2

LKB1 phosphorylates PAR-1 at the T408 site xref .|LKB1 thus positively regulates PAR-1 at the postsynapse.

SIGNOR-278992

Q13224

P12931

0

phosphorylation

up-regulates activity

0.559

We have investigated the tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B by exogenous Src Phosphorylation-site specific antibodies identified NR2B Tyr1472 as a phosphorylation site for intrinsic PSD tyrosine kinases

SIGNOR-247180

Q9HAW4

O00311

0

phosphorylation

up-regulates activity

0.742

Cdc7 phosphorylates Claspin in a manner dependent on AP and inhibits N\u2013C interaction.|Thus, Cdc7-ASK may activate DNA and PCNA bindings of Claspin through AP-mediated phosphorylation.

SIGNOR-279360

Q13882

P60484

0

dephosphorylation

down-regulates activity

0.416

PTEN inhibits PTK6 activity and downstream signaling in prostate cancer cells.|Using an in vitro phosphatase assay, we observed that PTEN was able to dephosphorylate PTK6 at tyrosine residue 342 in a dose dependent manner.

SIGNOR-276975

P28482

P23443

1

phosphorylation

up-regulates

0.596

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

SIGNOR-28800

P15311

P00533

0

phosphorylation

up-regulates

0.529

Ezrin was initially identified as a substrate for tyrosine phosphorylation by egfr (bretscher, 1989) and phosphorylation of residues y145 and y353 were detected to high stoichiometry after egf treatment . Phosphorylation of ezrin at y353 has been delineated to signal survival during epithelial cell differentiation via the phosphatidylinositol 3-kinase (pi3k)/akt pathway.

SIGNOR-133215

P16949

Q13153

0

phosphorylation

down-regulates

0.374

The hgf-induced wave2 transport, lamellipodia formation, stathmin/op18 phosphorylation at ser38 and binding to kinesin-wave2 complex, but not stathmin/op18 phosphorylation at ser25 and microtubule growth, were abrogated by pak1 inhibitor ipa-3

SIGNOR-183503

Q07812

P31749

0

phosphorylation

down-regulates activity

0.486

Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophilsWe suggest that Bax is regulated by phosphorylation of Ser(184) in an Akt-dependent manner and that phosphorylation inhibits Bax effects on the mitochondria by maintaining the protein in the cytoplasm, heterodimerized with antiapoptotic Bcl-2 family members

SIGNOR-252538

Q13131

Q8WUI4

1

phosphorylation

down-regulates

0.273

Another recently described set of transcriptional regulators targeted by ampk and its related family members across a range of eukaryotes are the class iia family of histone deacetylases (hdacs).

SIGNOR-176491

Q92696

P20339

1

lipidation

up-regulates activity

0.625

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-265572

Q9H093

Q15831

0

phosphorylation

up-regulates

0.273

A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold.

SIGNOR-122717

Q13191

P42226

1

ubiquitination

down-regulates quantity

0.2

Having shown that Cbl-b negatively regulates Stat6, we further investigated the mechanism of this regulation by determining whether Cbl-b associates with Stat6.|Our data demonstrate that Stat6 is ubiquitinated at K108 and K398 by Cbl-b, and that Stat6 ubiquitination is a critical post-translational regulatory mechanism for Stat6.

SIGNOR-278806

Q13547

Q00987

0

ubiquitination

down-regulates quantity by destabilization

0.468

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

SIGNOR-278761

P27987

P17612

0

phosphorylation

down-regulates activity

0.351

Two isoforms of the inositol 1,4,5-trisphosphate 3-kinase have been identified, the A form and the B form. phosphorylation of isoform A by the cyclic AMP-dependent protein kinase increased activity 1.5-fold, whereas phosphorylation of isoform B decreased activity by 45%. major phosphorylation sites in the protein are Ser119 for PKA. Ser119 in the A isoform is conserved in the B isoform as Ser328

SIGNOR-249995

Q6UB99

Q16620

1

transcriptional regulation

up-regulates quantity by expression

0.2

Ankrd11 knockdown decreases the levels of bdnf and Trkb mRNAs. Next, we examine whether ANKRD11 accesses the Trkb promoter in cortical neurons. We performed the chromatin immunoprecipitation assay (ChIP) using an ANKRD11 antibody followed by PCR to amplify the Trkb promoter region. We found that ANKRD11 binds to the Trkb promoter (Fig. 6E). As expected, the level of ANKRD11 binding was decreased in the Ankrd11 knockdown condition.

SIGNOR-266731

P07948

P20273

1

phosphorylation

down-regulates activity

0.743

LYN is a BCR-associated SRC kinase involved in the positive regulation of BCR, but it also functions as a negative regulator by phosphorylating the immunoreceptor tyrosine-based inhibitory motifs (ITIMs) of CD22.

SIGNOR-268443

O60674

P02647

1

null

up-regulates activity

0.298

ApoA-I interactions with ABCA1 and lipid efflux to apoA-I were substantially impaired by inhibiting or abolishing JAK2, whereas ABCA1 protein levels were unaffected, and ABCA1 cholesterol translocase activity was only slightly reduced. The most likely explanation for these findings is that JAK2 promotes apolipoprotein interactions with ABCA1 or a closely proximal site, and this facilitates the removal of cellular lipids. the interaction of apolipoproteins with ABCA1-expressing cells activates JAK2, which in turn activates a process that enhances apolipoprotein interactions with ABCA1 and lipid removal from cells

SIGNOR-252107

Q14653

P05231

1

transcriptional regulation

up-regulates quantity by expression

0.406

Recent reports show that in mice the microbiome, comprising commensal microorganisms that colonize body surfaces, promotes a partial and low-grade M1-like phenotype in macrophages throughout the body, including those in lymphoid organs (119, 120). This M1-like priming of macrophages induces chromatin remodeling with increased H3K4me3 marks at Ifnb, Il6, and Tnf promoters, which is associated with increased binding of NF-κB p65, IRF3, and Pol II upon cell stimulation

SIGNOR-251721

P28482

Q96LC9

1

phosphorylation

up-regulates

0.253

Phosphomimetic mutation of this site (s74d) moderately enhanced bmf apoptotic activity in vivo.22 here, we demonstrate a previously unrecognized mode of regulation of bmf. We show that b-raf-mek-erk2 signaling regulates bmf phosphorylation at serine 74 and serine 77. Phosphorylation of serine 77 downregulates the pro-apoptotic activity of bmf.

SIGNOR-195475

Q5T0T0

P01903

1

polyubiquitination

down-regulates quantity by destabilization

0.2

Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination.

SIGNOR-271411

P45974

P0CG48

1

cleavage

up-regulates quantity

0.847

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

SIGNOR-270822

P23508

Q13535

0

phosphorylation

up-regulates activity

0.2

MCC is phosphorylated at the ATM/ATR consensus sites Ser118 and Ser120. Finally, mutation of S118/120 to alanine did not affect MCC nuclear shuttling following UV but did impair MCC G2/M checkpoint activity.

SIGNOR-273514

Q96J02

Q9UBN4

1

ubiquitination

down-regulates activity

0.35

Ubiquitination of TRPV4 is dramatically increased by the HECT (homologous to E6-AP carboxyl terminus)-family ubiquitin ligase AIP4 without inducing degradation of this channel. Instead, AIP4 promotes the endocytosis of TRPV4 and decreases its amount at the plasma membrane.

SIGNOR-272624

P51452

P04626

1

dephosphorylation

down-regulates activity

0.268

Expression of VHR inhibited the activation of phospholipase Cγ and protein kinase C, both downstream effectors of Tyr-992 phosphorylation of EGFR. | We found that VHR decreased ErbB2 phosphorylation in vitro and in a cellular context, and the dephosphorylation of ErbB2 was more evident at Tyr-877 and Tyr-1221 than those at Tyr-1139 and Tyr-1248 (supplemental Fig. S1). Our data indicated that VHR was a cellular PTP against EGFR and ErbB2.

SIGNOR-248533

Q01130

Q92993

0

acetylation

down-regulates

0.466

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

SIGNOR-170594

O15354

O60260

0

ubiquitination

down-regulates quantity by destabilization

0.2

Parkin is a protein of 465 amino acids, and its structure includes a ubiquitin homologous domain in its N terminus and two RING finger domains in its C terminus. Molecular studies have determined that parkin is an E3 ubiquitin ligase function, implicating parkin in the ubiquitin-proteasome system, and raising the possibility that mutations in the gene lead to loss or diminished function. Three substrates for the ubiquitin-ligase function of parkin have been identified to date.1. A 22kDa glycosolated form of alpha-synuclei|2. Parkin-associated endothelin receptor-like receptor (Pael-R).

SIGNOR-249706

P54764

O00712

0

transcriptional regulation

up-regulates quantity

0.2

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268901

O00429

P49841

0

phosphorylation

up-regulates activity

0.388

We identified glycogen synthase kinase (GSK)3β-dependent Drp1 phosphorylation at Ser(40) and Ser(44), which increases Drp1 GTPase activity and its mitochondrial distribution and could induce mitochondrial fragmentation.

SIGNOR-276849

Q13535

Q8WXE1

1

phosphorylation

up-regulates

0.878

When dna is damaged, the atr-atrip complex is recruited to chromatin and is activated to transduce the checkpoint signal, but the precise kinase activation mechanism remains unknown. Here, we show that atrip is phosphorylated in an atr-dependent manner after genotoxic stimuli. The serine 68 and 72 residues are important for the phosphorylation in vivo and are required exclusively for direct modification by atr in vitro.

SIGNOR-129473

Q9NR48

Q9ULB1

1

transcriptional regulation

down-regulates quantity by repression

0.259

Our results reveal that a novel process of activity-dependent transcriptional repression exists in neurons and that Ash1L mediates the long-term repression of nrxn1α, thus implicating an important role for epigenetic modification in brain functioning.

SIGNOR-269056

O95865

Q9UHD2

0

phosphorylation

down-regulates activity

0.2

TANK-binding kinase 1 (TBK1), a kinase downstream of MAVS, inhibited DDAH2 by phosphorylating DDAH2 at multiple sites. |The T203D, T211D, S245D, and S253D mutations significantly reduced the inhibitory effect of DDAH2 on RLR signaling, suggesting that phosphorylation of these residues was critical for DDAH2 to inhibit activation o

SIGNOR-275648

Q9UQB9

P68431

1

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

P13612

P17612

0

phosphorylation

up-regulates activity

0.494

PKA phosphorylationin vitro blocks the binding of the alpha4 tail to paxillin. A mutation that mimics alpha4 phosphorylation disrupts paxillin binding and promotes cell spreading

SIGNOR-110119

P16104

Q13535

0

phosphorylation

up-regulates activity

0.2

ATR and ATM also phosphorylate histone H2AX at Ser 139 (gammaH2AX) in response to DNA double-strand breaks (DSBs), which spreads along the DNA up to 200-400 kb and helps in the recruitment of proteins involved in DNA damage repair and checkpoint activation .

SIGNOR-279356

Q05655

P19429

1

phosphorylation

up-regulates activity

0.272

Src phosphorylates pkcdelta at tyr311 and tyr332 leading to enhanced pkcdelta autophosphorylation at thr505 (its activation loop) and pkcdelta-dependent ctni phosphorylation at both ser23/ser24 and thr144.

SIGNOR-178880

P31749

P29474

1

phosphorylation

up-regulates

0.877

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 a on serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no.

SIGNOR-112363

P24941

Q96EB6

1

phosphorylation

up-regulates activity

0.465

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

SIGNOR-279513

Q66PJ3

Q96BR1

0

phosphorylation

down-regulates activity

0.2

AIP4 is phosphorylated by CISK in vitro on WW domain residues, which may impact its ability to interact with and ubiquitinate substrate proteins.|Expression of a constitutively active CISK inhibits CXCR4 degradation, possibly by attenuating CXCR4 binding to and ubiquitination by AIP4 and/or modulating the action of AIP4 on a protein involved in CXCR4 endosomal sorting .

SIGNOR-280124

Q13043

Q9Y243

0

phosphorylation

down-regulates

0.261

Full activation of mst1 requires an activation cleavage that is prevented by the phosphorylation of thr-387 by akt.

SIGNOR-201129

Q8IXW5

P24928

1

dephosphorylation

up-regulates activity

0.738

In addition, we show that RPAP2 is a CTD Ser5 phosphatase. Taken together, our results indicate that during transcription of snRNA genes, Ser7 phosphorylation facilitates recruitment of RPAP2, which in turn both recruits Integrator and dephosphorylates Ser5.|The Pol II CTD is first phosphorylated on Ser5 and then on Ser7 by CDK7. RPAP2 associates with the Pol II CTD after Ser7 phosphorylation and tethers a subcomplex of Integrator to snRNA genes. RPAP2 dephosphorylates Ser5P of the CTD, facilitating transcription and the subsequent recruitment of the Int11 catalytic subunit of Integrator

SIGNOR-248748

O15164

P04637

1

ubiquitination

down-regulates

0.532

New ring-domain e3-ubiquitin ligase trim24 that targets p53 for degradation

SIGNOR-188726

P32243

P14651

0

transcriptional regulation

up-regulates quantity by expression

0.2

Transactivation of the mouse OTX2 Luc constructs by the human HOXB1, HOXB2, and HOXB3 proteins. | Likewise, the construct pOTX2LucΔ−710 showed an 8-, 12-, and 6-fold increase in transcriptional activity if co-transfected with pSG-HOXB1, -HOXB2, and -HOXB3, respectively

SIGNOR-261635

P27695

Q92911

1

transcriptional regulation

up-regulates quantity by expression

0.2

These data demonstrate a role for APE/Ref-1 protein in the transcriptional regulation of NIS gene expression by itself and in cooperation with PAX8.

SIGNOR-261564

P67775

P23443

1

dephosphorylation

down-regulates

0.72

Protein phosphatase 2a inactivates the mitogen-stimulated s6 kinase from swiss mouse 3t3 cells

SIGNOR-23575

Q05397

Q9UQM7

0

phosphorylation

up-regulates

0.272

Furthermore, activated camkii directly phosphorylated the recombinant cooh-terminal region of fak at a residue equivalent to ser-843.

SIGNOR-135631

P23470

O60496

1

dephosphorylation

up-regulates activity

0.2

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254698

Q14493

Q99877

1

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-265392

Q13322

P12931

0

phosphorylation

down-regulates

0.447

Grb10 tyrosine phosphorylation was stimulated by expression of constitutively active src or fyn in cells and by incubation with purified src or fyn in vitro. The insulin stimulated or src/fyn-mediated tyrosine phosphorylation in vivo was significantly reduced when grb10 tyrosine 67 was changed to glycine. This mutant form of grb10 bound with higher affinity to the ir in cells than that of the wild-type protein, suggesting that tyrosine phosphorylation of grb10 may normally negatively regulate its binding to the ir.

SIGNOR-78706

P13569

Q99942

0

ubiquitination

down-regulates quantity by destabilization

0.665

JB12 cooperates with cytosolic Hsc70 and the ubiquitin ligase RMA1 to target CFTR and CFTRΔF508 for degradation.

SIGNOR-271494

O43561

P27361

0

phosphorylation

down-regulates

0.304

Lat, an adapter protein essential for t-cell signaling, is phosphorylated at its thr 155 by erk in response to t-cell receptor stimulation. Thr 155 phosphorylation reduces the ability of lat to recruit plcgamma1 and slp76, leading to attenuation of subsequent downstream events such as [ca2+]i mobilization and activation of the erk pathway.

SIGNOR-125770

Q149N8

P12004

1

ubiquitination

up-regulates

0.553

We provide evidence that similar to rad5, shprh physically interacts with the human rad6rad18 and mms2ubc13 protein complexes, and importantly, we show that it exhibits an ubiquitin ligase activity and mediates mms2ubc13-dependent polyubiquitylation of pcna. Thus, shprh is a functional homolog of rad5.

SIGNOR-187757

Q13618

Q03933

1

ubiquitination

down-regulates quantity by destabilization

0.326

Here we show that the PEST sequences of a short-lived protein called HSF2 interact with Cullin3, a subunit of a Cullin-RING E3 ubiquitin ligase, and that this interaction mediates the Cul3-dependent ubiquitination and degradation of HSF2

SIGNOR-239129

Q9H165

P69891

1

transcriptional regulation

down-regulates quantity by repression

0.446

Our findings reveal that direct γ-globin gene promoter repression by BCL11A underlies hemoglobin switching.

SIGNOR-269067

Q99717

O95257

1

transcriptional regulation

up-regulates quantity

0.2

Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation

SIGNOR-268942

O43315

Q05513

0

phosphorylation

up-regulates

0.2

Wt-pkc_-mediated phosphorylation of wt aqp9 in vitro. In the experiments, substitution of ser11 to ala markedly inhibited phosphorylation. the s11a mutation in fibroblasts caused a smoother cell periphery with fewer aqp9-induced filopodia

SIGNOR-176278

P03372

P11511

1

transcriptional regulation

down-regulates quantity by repression

0.516

By binding to S1, ERalpha down-regulates the aromatase promoter activity.

SIGNOR-271683

P48729

Q12968

1

phosphorylation

down-regulates activity

0.59

Dominant-negative cki alpha Induces nuclear import of nf-at4 these results demonstrated that the cki alpha Phosphorylation sites identified in vitro were also specifically phosphorylated by cki alpha In vivo, and that these residues were crucial for the masking of the nls of nf-at4.

SIGNOR-109781

P06239

Q9NRW4

0

dephosphorylation

down-regulates activity

0.273

Because JKAP dephosphorylates and inactivates Lck in T cells [ xref ], we studied whether JKAP downregulation results in Lck activation in SLE T cells.

SIGNOR-277148

P10636

P43405

0

phosphorylation

down-regulates

0.466

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

SIGNOR-159648

Q9UGL1

P78317

0

sumoylation

down-regulates quantity by destabilization

0.3

Hendriks and coworkers showed that, in response to alkylation damage by methyl methanesulfonate (MMS), SUMOylated JARID1B (KDM5B) is ubiquitylated by the SUMOtargeted ubiquitin ligase RNF4 and degraded by the proteasome, whereas JARID1C (KDM5C) is SUMOylated and recruited to the chromatin to demethylate histone H3K4 (Hendriks et al., 2015).

SIGNOR-271575

P62979

Q93008

0

cleavage

up-regulates quantity

0.504

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

SIGNOR-270826

P51608

O15111

0

phosphorylation

up-regulates activity

0.2

Representative confocal micrographs of 4th day differentiating cultures are shown. (C) IKK\u03b1 promotes MeCP2-dependent BDNF expression.|The characterization of IKK\u03b1-mediated phosphorylation of MeCP2 at Ser421 and other residues and their effects on the activity of MeCP2 is a topic of current work in our laboratory.

SIGNOR-279459

P35558

Q8IXJ6

0

deacetylation

up-regulates quantity by stabilization

0.426

Conversely, SIRT2 deacetylates and stabilizes PEPCK1.|Furthermore, coexpression of P300 increased acetylation levels of wild-type PEPCK1, but not PEPCK13K/R, indicating that P300 acts on these lysine residues of PEPCK1

SIGNOR-267599

P31749

Q07352

1

phosphorylation

down-regulates

0.657

Here we report that protein kinase b (pkb/akt) stabilizes are transcripts by phosphorylating brf1 at serine 92 (s92). Recombinant brf1 promoted in vitro decay of are-containing mrna (are-mrna), yet phosphorylation by pkb impaired this activity.

SIGNOR-130376

P12931

P30411

1

phosphorylation

up-regulates

0.262

Here we demonstrate that egf is capable of inducing src-mediated phosphorylation of the tyrosine residues 177 and 347 of bkr. Their replacement by phenylalanine led to bkr mutants which are unable to activate the camp pathway.

SIGNOR-141103

Q12955

Q6ZMI3

0

relocalization

up-regulates quantity

0.41

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

SIGNOR-266725

P42224

Q07912

0

phosphorylation

up-regulates activity

0.357

Hence, ACK1 activates STAT1 through its kinase activity.|We found that wild-type ACK1 and to a larger extent constitutively active ACK1 increased the phosphorylation of cytoplasmic STAT1 at Y701.

SIGNOR-278348

Q16666

P68400

0

phosphorylation

up-regulates activity

0.321

Here we examine the functionality of the interferon-induced factor 16 (IFI 16) CcN motif, demonstrating its ability to target a heterologous protein to the nucleus, and to be phosphorylated specifically by the CcN-motif-phosphorylating protein kinase CK2 (CK2). | Specific phosphorylation of IFI 16 Ser132 in HeLa cell extracts and by purified CK2 in vitro

SIGNOR-250902

P53350

Q9NYZ3

1

phosphorylation

up-regulates

0.736

In this study, we show that g2 and s-phase-expressed 1 (gtse1) protein, a negative regulator of p53, is required for g2 checkpoint recovery and that plk1 phosphorylation of gtse1 at ser 435 promotes its nuclear localization, and thus shuttles p53 out of the nucleus to lead to its degradation during the recovery.

SIGNOR-166417

P46527

P28482

0

phosphorylation

up-regulates

0.346

Phosphorylation on ser-10 of kip1 is the major site of phosphorylation in resting cells, takes place at the g(0)-g1 phase and leads to protein stability.

SIGNOR-77651

P25054

P49841

0

phosphorylation

up-regulates

0.758

Gsk-3beta-dependent phosphorylation of apc.

SIGNOR-75366

O75030

P16220

0

transcriptional regulation

up-regulates quantity by expression

0.633

Therefore, the molecular steps linking cAMPto melanogenesis up-regulation appear currently better elucidated. cAMP activates PKA, and PKA phosphorylates and activates CREB which, when activated, binds to the CRE domain present in the microphthalmia promoter,thereby up-regulating its transcription.

SIGNOR-249619

Q08209

O95644

1

dephosphorylation

up-regulates

0.825

Calcineurin directly dephosphorylates nfat resulting in the nuclear import of nfat.

SIGNOR-176370

P05771

P41594

1

phosphorylation

up-regulates activity

0.354

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-249286

Q9NX09

O60260

0

ubiquitination

down-regulates quantity by destabilization

0.2

In conclusion, our work in cellular and animal models and in human samples strongly indicates that RTP801 is a substrate of parkin and that RTP801 elevation due to parkin loss of function in both AR-JP and sporadic Parkinson's disease may contribute to neurodegeneration.|We showed that parkin poly-ubiquitinates RTP801, both in vitro and in vivo.

SIGNOR-278560

P31270

P01236

1

transcriptional regulation

up-regulates quantity by expression

0.351

HoxA-11 enhanced upregulation of PRL only in differentiated cells.

SIGNOR-261630

Q14493

P0C5Z0

1

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

Q9UPN4

P49137

0

phosphorylation

down-regulates quantity

0.291

We identify CEP131 as a major Centriolar satellites-associated substrate of p38-dependent, MK2-mediated phosphorylation on two defined residues and show that these modifications promote binding to 14-3-3 proteins, in turn leading to cytoplasmic sequestration of CEP131 and associated Centriolar satellites factors.|We therefore conclude that MK2 dependent phosphorylation of CEP131 at S47 and S78 and the ensuing binding of 14-3-3 proteins play an essential role in triggering stress induced remodelling of CS.

SIGNOR-278181

Q06330

Q16539

0

phosphorylation

down-regulates quantity by destabilization

0.247

P38 MAPK phosphorylates RBP-Jk at Thr339 by physical binding, which subsequently induces the degradation and ubiquitylation of the RBP-Jk protein.

SIGNOR-276403

Q9UKT6

P49841

0

phosphorylation

up-regulates activity

0.2

GSK-3beta phosphorylates FBXL21 and TCAP to activate FBXL21-mediated, phosphodegron-dependent TCAP degradation.|These results show direct GSK-3beta phosphorylation of TCAP S157 and FBXL21 T33 sites.

SIGNOR-264851

Q96RR4

P49840

0

phosphorylation

down-regulates

0.269

Cdk5 and gsk3 phosphorylate ser-129, ser-133, and ser-137. Mutation of ser-129, ser-133, and ser-137 increases autonomous activity with little change in ca2 /cam-dependent activity.

SIGNOR-198122

P04629

Q9BV47

0

dephosphorylation

down-regulates activity

0.371

NEAP and DUSP26 dephosphorylated TrkA and FGFR1 directly.|We found that NEAP, but not its phosphatase-defective mutant, suppressed nerve growth factor (NGF) receptor TrkA and fibroblast growth factor receptor 1 (FGFR1) activation in PC12 cells

SIGNOR-277105

P52333

O95644

1

phosphorylation

up-regulates activity

0.383

Here we found that IL-7-Jak3 signals activated the transcription factor NFATc1 in DN thymocytes by phosphorylating Tyr371 in the regulatory region of NFATc1.

SIGNOR-276435

P61006

Q5S007

0

phosphorylation

up-regulates activity

0.33

In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. |Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease

SIGNOR-260267

P78536

P15941

1

cleavage

down-regulates

0.308

These characteristics along with studies conducted with cell lines genetically deficient in various adams (for a disintegrin and metalloprotease) identified tumor necrosis factor-alpha converting enzyme (tace)/adam 17 as a muc1 sheddase.

SIGNOR-95630