GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P25963	Q9HC78	0	transcriptional regulation	down-regulates quantity by repression	0.259	ChIP and next generation high-throughput DNA sequencing assay showed that ZBTB20 specifically bound to IκBα gene promoter (+1 to +60 region) after TLR activation. ZBTB20 could inhibit IκBα gene transcription, govern IκBα protein expression, and then promote NF-κB activation. Therefore, transcriptional repressor ZBTB20 is needed to promote full activation of TLR signaling and TLR-triggered innate immune response by selectively suppressing the suppressor IκBα gene transcription.	SIGNOR-266868
P61586	Q02156	0	phosphorylation	up-regulates activity	0.439	Our laboratory reported that PKCepsilon modulates RhoA activity in HNSCC presumably through posttranslation phosphorylation .\|Phosphopeptide mapping revealed that PKCepsilon phosphorylates RhoA at T127 and S188.	SIGNOR-279478
Q15561	P29279	1	transcriptional regulation	up-regulates quantity by expression	0.2	The multifunctional cytokine TGF-β has been identified as a potent inducer of CTGF expression, activating CTGF transcription through the canonical Smad signaling pathway. It is worth noting that TGF-β synergizes with Hippo–Yes-associated protein (YAP) signaling, a key regulator of tumorigenesis, to induce the expression of CTGF by the formation of a YAP-TEAD4-Smad3-p300 complex on the CTGF promoter	SIGNOR-277686
P53350	P67809	1	phosphorylation	up-regulates quantity	0.253	Here we identify that PLK1 inhibition can induce apoptosis and DNA damage of GSCs, we have also delineat the possible underlying molecular mechanisms: PLK1 interacts with YBX1 and directly phosphorylates serine 174 and serine 176 of YBX1.\|Inhibition of PLK1 reduces the phosphorylation level of YBX1, and decreased phosphorylation of YBX1 prevents its nuclear translocation, thereby inducing apoptosis and DNA damage of GSCs.	SIGNOR-279255
Q9UQC2	O60674	0	phosphorylation	up-regulates	0.515	In vitro, activated jak2 directly phosphorylated specific gab2 tyrosine residues. Mutagenesis studies revealed that gab2 tyrosine 643 (y643) was a major target of jak2 in vitro, and a key residue for jak2-dependent phosphorylation in intact cells. Mutation of gab2 y643 inhibited g-csf-stimulated erk1/2 activation and shp2 binding to gab2.	SIGNOR-179488
P18507	Q02156	0	phosphorylation	down-regulates activity	0.233	Protein kinase C epsilon regulates gamma-aminobutyrate type A receptor sensitivity to ethanol and benzodiazepines through phosphorylation of gamma2 subunits. Our findings indicate that PKCepsilon phosphorylation of gamma2 regulates the response of GABA(A) receptors to specific allosteric modulators, and, in particular, PKCepsilon inhibition renders these receptors sensitive to low intoxicating concentrations of ethanol.	SIGNOR-263174
P17612	P24390	1	phosphorylation	up-regulates	0.309	We conclude that pka phosphorylation of serine 209 is required for the retrograde transport of the kdel receptor from the golgi complex to the er from which the retrieval of proteins bearing the kdel signal depends.	SIGNOR-118257
Q12791	P17252	0	phosphorylation	up-regulates	0.2	Results showed that mutating s1076 altered the effect of pkc activation on bk(ca) channels in hek-293 cells	SIGNOR-186755
P17612	Q01082	1	phosphorylation	down-regulates activity	0.331	Short C-terminal splice variant of betaII-spectrin (betaIISigma2) is a substrate for phosphorylation. protein kinase A phosphorylates Thr-2159. Mammalian alphaII- and betaII-spectrin subunits form dimers that associate head to head with high affinity to form tetramers In vitro, protein kinase A phosphorylation of an active fragment of betaIISigma2 greatly reduced its interaction with alphaII-spectrin at the tetramerization site.	SIGNOR-250054
P23025	O95714	0	ubiquitination	down-regulates	0.385	Herc2 may ubiquitinate xpa and thus target it for proteolytic degradation	SIGNOR-164595
Q13698	P67870	0	phosphorylation	up-regulates activity	0.2	To identify the regulatory sites of phosphorylation under physiologically relevant conditions, Ca(V)1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac Ca(V)1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that Ca(V)1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas Ca(V)1.1-T1579 is a substrate for casein kinase 2.	SIGNOR-263115
O43819	P04637	0	transcriptional regulation	up-regulates quantity by expression	0.64	P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway.	SIGNOR-267463
O43684	Q13315	0	phosphorylation	up-regulates activity	0.312	Taken together, we highlight the functional significance of the crosstalk between the kinetochore-oriented signal and double-strand break repair pathways via ATM phosphorylation of Bub3 on Ser135.	SIGNOR-277582
P14091	P01023	1	cleavage	down-regulates quantity by destabilization	0.38	Disruption of structural and functional integrity of alpha 2-macroglobulin by cathepsin E\|Analysis of the N-terminal amino-acid sequences of these proteins revealed that alpha 2M was selectively cleaved at the Phe811-Leu812 bond in about 100mer downstream of the bait region.	SIGNOR-266977
P30530	Q63HR2	1	phosphorylation	up-regulates quantity	0.2	In this study, however, we demonstrate for the first time that Axl directly binds to and phosphorylates TNS2 at Y483.\|Overall these results suggest that Axl positively regulates TNS2 expression.	SIGNOR-278471
Q12955	O94856	0	relocalization	up-regulates quantity	0.745	Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.	SIGNOR-266717
P06493	P19525	0	phosphorylation	down-regulates	0.328	Our findings demonstrate that (i) pkr, ser/thr kinase, phosphorylates its new substrate cdc2 at the tyr 4 residue, (ii) pkr-mediated tyr 4-phosphorylation facilitates cdc2 ubiquitination and proteosomal degradation	SIGNOR-164809
Q92769	P67775	0	dephosphorylation	down-regulates activity	0.281	In contrast, in the present work, PPP2CA reduced HDAC2 S394 phosphorylation.\|We postulated that PPP2CA would negatively regulate phospho dependent HDAC2 activity.	SIGNOR-277049
Q9BY41	P04637	1	deacetylation	down-regulates activity	0.456	HDAC8 mediates CM-induced deacetylation of p53.Collectively, these results indicate that although binding to p53 and HDAC8 occurs through distinct regions of the CM protein, simultaneous interaction with HDAC8 and p53 is required for aberrant deacetylation and inactivation of p53.	SIGNOR-255738
Q13541	P19784	0	phosphorylation	down-regulates activity	0.333	The kinase is quite distinct from casein kinase 2, which also phosphorylates Ser-111 of 4E-BP1. The possible importance of these kinases in the phosphorylation of 4E-BP1 in fat cells is discussed. It is suggested that the phosphorylation of Ser-111 might be a priming event that facilitates the subsequent phosphorylation of Thr-36, Thr-45, Ser-64 and Thr69 by a rapamycin-sensitive process that initiates the dissociation of 4E-BP1 from eIF4E and hence the formation of the eIF4F complex.	SIGNOR-249334
Q13315	P54646	1	phosphorylation	up-regulates activity	0.264	ATM phosphorylates AMPKalpha2 to induce inhibitory phosphorylation of HIPK2\|	SIGNOR-275488
Q9BYF1	P01019	1	cleavage	up-regulates activity	0.759	The ACE2 hydrolytic activity is dependent on the C terminus sequence of the substrate, which is evident from the data with the angiotensin peptides. After 2 h, ACE2 hydrolyzes Ang I partially and Ang II completely, although there is no hydrolysis of angiotensin 1–9, angiotensin 1–7, and angiotensin 1–5, which possess the same N terminus.	SIGNOR-256315
P40692	P00519	0	phosphorylation	up-regulates quantity by stabilization	0.344	We also observed phosphorylation of MLH1 by ABL1 in an in vitro kinase assay with purified recombinant ABL1 and MLH1, confirming there is a direct phosphorylation between ABL1 and the MLH1 component of the MLH1-PMS2 heterodimer.\|we propose that ABL1 prevents MLH1 from being targeted for degradation by the chaperone Hsp70 and that in the absence of ABL1 activity at least a portion of MLH1 is degraded.	SIGNOR-279581
Q13535	P16104	1	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
P35712	P63279	0	sumoylation	down-regulates activity	0.367	We show that SOX6 is modified in vitro and in vivo by small ubiquitin‐related modifier (SUMO) on two distinct sites. Mutation of both sites abolished SOX6 sumoylation and increased SOX6 transcriptional activity. SUMO dependent repression of SOX6 transcription was promoted by UBC9 whereas siRNA to UBC9, cotransfection of inactive UBC9 or a SUMO protease increased SOX6 transcriptional activity.	SIGNOR-256130
Q99728	P24941	0	phosphorylation	down-regulates activity	0.609	CDK2-cyclin A1/E1 and CDK1-cyclin B1 phosphorylate BARD1 on its NH(2) terminus in vivo and in vitro. 44999999="E1" 45999998="terminus"}\|Here we show that the ubiquitin ligase activity of BRCA1-BARD1 is down-regulated by CDK2.	SIGNOR-280211
Q06187	P78347	1	phosphorylation	up-regulates activity	0.517	These residues, tyr248, tyr357, and tyr462, were also found to be the major sites for btk-dependent phosphorylation of bap/tfii-i in vivo. Residues tyr357 and tyr462 are contained within the loop regions of adjacent helix-loop-helix-like repeats within bap/tfii-i. Mutation of either tyr248, tyr357, or tyr462 to phenylalanine reduced transcription from a c-fos promoter relative to wild-type bap/tfii-i in transfected cos-7 cells, consistent with the interpretation that phosphorylation at these sites contributes to transcriptional activation.	SIGNOR-108346
Q92911	P27695	0	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
Q9Y618	P06401	1	acetylation	down-regulates	0.588	In this study we assessed the effect of smrt and dax-1 on ar and pr activity in the presence of both agonists and partial antagonists. We show that smrt and dax-1 repress agonist-dependent activity of both receptors, and the mechanism of repression includes disruption of the receptor dimer interactions rather than recruitment of histone deacetylases.	SIGNOR-101289
Q9H1B7	P01210	1	transcriptional regulation	down-regulates quantity by repression	0.307	EAP1 encoded a nuclear protein expressed in neurons involved in the inhibitory and facilitatory control of reproduction. EAP1 transactivated genes required for reproductive function, such as GNRH1, and repressed inhibitory genes, such as preproenkephalin. It contained a RING finger domain of the C3HC4 subclass required for this dual transcriptional activity.These results suggest that EAP1 is a transcriptional regulator that, acting within the neuroendocrine brain, contributes to controlling female reproductive function.	SIGNOR-267155
P53779	P04637	1	phosphorylation	up-regulates	0.628	The targets of jnk include the transcription factors p53. P75ntr-mediated apoptosis was shown to be dependent of p53	SIGNOR-120552
P47712	O75582	0	phosphorylation	up-regulates activity	0.352	Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases.	SIGNOR-249051
P19174	P16234	0	phosphorylation	up-regulates	0.65	Tyrosine phosphorylation has been shown to increase the enzymatic activity of plc-? / we show that the human pdgf ?- And ?-Receptors differ quantitatively in their abilities to associate with and phosphorylate plc-? And to stimulate inositol phosphate production.	SIGNOR-28176
Q05655	P35236	1	phosphorylation	up-regulates activity	0.2	HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.	SIGNOR-276048
O14672	P22415	0	transcriptional regulation	up-regulates quantity by expression	0.27	The promoter region of ADAM10 contains several transcription factor binding sites that can stimulate its transcription. These include binding sites for transcription factors SP1 and USF, and the spliced form of the X-box binding protein (XBP)-1 as well as a retinoic acid-responsive element	SIGNOR-259837
P04070	P38435	0	carboxylation	up-regulates activity	0.572	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-265925
Q9UMX1	P51955	0	phosphorylation	up-regulates activity	0.2	Intriguingly, Nek2A is found to stabilize SuFu at least partly depending on its kinase activity, thereby triggering phosphorylation of the SuFu protein.\|Nek2A phosphorylates and stabilizes SuFu: A new strategy of Gli2/Hedgehog signaling regulatory mechanism.	SIGNOR-279235
P04637	Q15831	0	phosphorylation	up-regulates	0.756	We show that lkb1 physically associates with p53 in the nucleus and directly or indirectly phosphorylates p53 ser15 (previously shown to be phosphorylated by amp-dependent kinase) and p53 ser392	SIGNOR-150830
P49841	P98170	1	phosphorylation	up-regulates activity	0.394	We now demonstrate that XIAP is phosphorylated by GSK3 at threonine 180, and that an alanine mutant (XIAPT180A) exhibits decreased Wnt activity compared to wild-type XIAP in cultured human cells and in Xenopus embryos.	SIGNOR-277390
Q68DV7	P04637	1	ubiquitination	down-regulates quantity by destabilization	0.451	Moreover, RNF43 polyubiquitinates p53 which further leads to its destabilization resulting in a decrease in induction of the p53 apoptotic pathway, a hitherto unknown process targeted by NP for p53 stabilization and accumulation.	SIGNOR-278714
P36888	P48735	1	phosphorylation	down-regulates activity	0.421	FLT3 promotes mIDH2 acetylation through Y107 phosphorylation of mIDH2 that enhances ACAT1 recruitment,	SIGNOR-267632
P31749	P62140	0	dephosphorylation	down-regulates activity	0.386	Here, we identify PP1 as a serine/threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells\|The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells	SIGNOR-252604
P48431	P24941	0	phosphorylation	up-regulates activity	0.394	Cdk2 physically interacts with Sox2 and phosphorylates Sox2 at Ser 39 and Ser 253 in vitro.	SIGNOR-279448
P10586	P19174	1	dephosphorylation	down-regulates	0.2	Here we show that lar reduces the constitutive tyrosine autophosphorylation and kinase activity of ret-men2a but not ret-men2b, accompanying a significant decrease of phosphorylation of phospholipase cgamma, akt, and erk1/2.	SIGNOR-85166
P0DP91	P00519	0	phosphorylation	up-regulates activity	0.271	These data raise the possibility that tyrosine phosphorylation of CSB by c-Abl promotes redistribution of CSB in the nucleus and enrichment of CSB in the nucleolus in response to oxidative stress	SIGNOR-279317
P84243	O14757	0	phosphorylation	down-regulates activity	0.2	We identify chk1 as the kinase responsible for h3-t11 phosphorylation. H3-t11 phosphorylation occurs throughout the cell cycle and is chk1 dependent in vivo.Phosphorylation at thr-12 (h3t11ph) by pkn1 is a specific tag for epigenetic transcriptional activation that promotes demethylation of lys-10 (h3k9me) by kdm4c/jmjd2c.	SIGNOR-160557
P28482	Q9UKX7	1	phosphorylation	down-regulates activity	0.2	Erk phosphorylates nup50 at ser221 and ser315 erk phosphorylation of the fg repeat region of nup50 reduced its affinity for importin-beta family proteins, importin-beta and transportin.	SIGNOR-188135
P30281	Q15759	0	phosphorylation	down-regulates quantity by destabilization	0.2	P38SAPK2 phosphorylates cyclin D3 at Thr-283 and targets it for proteasomal degradation.	SIGNOR-280023
P04637	P67775	0	dephosphorylation	down-regulates activity	0.59	Phosphorylation of p53 at serine 37 is important for transcriptional activity and regulation in response to DNA damage\| Furthermore, in vitro phosphatase assays show that PP2A dephosphorylates p53 at S37.	SIGNOR-248619
P45983	P16104	1	phosphorylation	up-regulates	0.2	The stress-response kinase jnk1, activated by dna damage and initiating a pro-apoptotic program, has been recently shown to translocate into the nucleus upon activation where it phosphorylates substrates including h2ax s139, an event critical for dna degradation mediated by caspase-activated dnase (cad) in apoptotic cells	SIGNOR-184146
Q9NRM7	P00519	1	phosphorylation	down-regulates activity	0.362	Inhibition of c-Abl by Lats2 was mediated through Lats2 interaction with and phosphorylation of c-Abl. Lats2 phosphorylates c-Abl at Thr197 in vitro.	SIGNOR-276497
P61586	O94989	0	guanine nucleotide exchange factor	up-regulates activity	0.571	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-260540
P11137	Q76NI1	0	phosphorylation	up-regulates activity	0.369	V-KIND enhances Thr phosphorylation of MAP2.	SIGNOR-278950
P78536	P07359	1	cleavage	down-regulates activity	0.284	GPIbα is shed by metalloproteases such as ADAM17, a process that releases a soluble GPIbα fragment termed glycocalicin. ADAM17 cleaves within the GPIbα-based peptide (LRGV465LK) through a mechanism that is only partially understood [42]. GPIbα shedding has been shown to be constitutive but it can be increased by activation of protein kinases C (PKC) or inhibition of calmodulin [42, 43]. Shedding leads to decreased receptor density	SIGNOR-261861
O00141	Q969H0	1	phosphorylation	up-regulates	0.291	Here, we report that the serum- and glucocorticoid-inducible protein kinase sgk1 remarkably reduced the protein stability of the active form of notch1 through fbw7activated sgk1 phosphorylated fbw7 at serine 227	SIGNOR-170404
P06241	P52757	1	phosphorylation	down-regulates	0.2	Ere we report that beta2-chimaerin is tyrosine-phosphorylated by src-family kinases (sfks) upon cell stimulation with epidermal growth factor (egf). these results suggest tyr-21 phosphorylation as a novel, sfk-dependent mechanism that negatively regulates beta2-chimaerin rac-gap activity.	SIGNOR-155709
Q03112	Q13315	0	phosphorylation	up-regulates activity	0.2	To investigate to what extent EVI1 function might be regulated by post-translational modifications we carried out mass spectrometry- and antibody-based analyses and uncovered an ATM-mediated double phosphorylation of EVI1 at the carboxy-terminal S858/S860 SQS motif.	SIGNOR-273433
P68431	P51812	0	phosphorylation	down-regulates activity	0.2	Phosphorylation at ser-11 (h3s10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or uv irradiation and result in the activation of genes, such as c-fos and c-jun.	SIGNOR-119229
P17302	P78415	0	transcriptional regulation	down-regulates quantity by repression	0.278	Irx3 directly represses Cx43 transcription	SIGNOR-266044
P30530	P07947	1	phosphorylation	up-regulates activity	0.2	Here, we show that EphA2, YES1, and ANXA2 form a signal axis, in which YES1 activated by EphA2 phosphorylates ANXA2 at Tyr24 site, leading to ANXA2 activation and increased ANXA2 nuclear distribution in gastric cancer (GC) cells.	SIGNOR-277555
Q8N5B7	P68400	0	phosphorylation	up-regulates activity	0.2	Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue.	SIGNOR-273987
Q13887	Q05655	0	phosphorylation	up-regulates activity	0.335	Phosphorylation of Kruppel-like factor 5 (KLF5/IKLF) at the CBP interaction region enhances its transactivation function. \| Inhibition of protein kinase activity by H7 or calphostin C blocked both full-length and N-terminal fragment (amino acids 1-238) KLF5 activities. Mutation at a potential protein kinase C phosphorylation site within the CBP interaction domain of KLF5 reduces its transactivation function. Furthermore, using the GST pull-down approach, we showed that phosphorylation of KLF5 enhances its interaction with CBP. The results of the present study provide a mechanism for KLF5 transactivation function. \| We found that KLF5s activity was reduced to half when the serine in the potential PKC phosphorylation site was mutated to alanine (Fig. 6B, S153A) Nonetheless, the S153A mutant still retains significant transactivation activity.	SIGNOR-249206
P42224	Q05655	0	phosphorylation	up-regulates	0.589	All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below).	SIGNOR-154791
Q9NZC9	Q13535	0	phosphorylation	down-regulates activity	0.538	ATR phosphorylates SMARCAL1 on S652, thereby limiting its fork regression activities and preventing aberrant fork processing. Thus, phosphorylation of SMARCAL1 is one mechanism by which ATR prevents fork collapse, promotes the completion of DNA replication, and maintains genome integrity.	SIGNOR-273516
Q13043	O95835	1	phosphorylation	up-regulates	0.623	We show that Mst2 and hWW45 interact with each other in human cells and that both Mst2 and Mst1 are able to phosphorylate Lats1 and Lats2, thereby stimulating Lats kinase activity.	SIGNOR-133551
P49137	Q6JBY9	1	phosphorylation	down-regulates activity	0.477	Human CapZIP was phosphorylated at Ser-179 and Ser-244 by MAPKAP-K2 (mitogen-activated protein kinase-activated protein kinase 2) or MAPKAP-K3 in vitro. In the present paper we have identified CapZIP as a protein that is phosphorylated exceptionally rapidly by several SAPKs in vitro (Figure 4), and which is expressed in muscles and immune cells. Both MAPKAP-K2 and MAPKAP-K3 phosphorylated CapZIP at Ser-179 in vitro. An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.	SIGNOR-263080
Q9BV68	P00533	1	polyubiquitination	down-regulates quantity by destabilization	0.328	RNF126 and Rabring7 associate with the EGFR through a ubiquitin-binding zinc finger domain and both E3 ubiquitin ligases promote ubiquitylation of EGFR. In HeLa cells depleted of either RNF126 or Rabring7 the EGFR is retained in a late endocytic compartment and is inefficiently degraded.	SIGNOR-272103
Q9BXW9	P68400	0	phosphorylation	down-regulates activity	0.2	Here, we report a cluster of phosphosites on FANCD2 whose phosphorylation by CK2 inhibits both FANCD2 recruitment to ICLs and its monoubiquitination in vitro and in vivo. We have found that phosphorylated FANCD2 possesses reduced DNA binding activity, explaining the previous observations.	SIGNOR-276730
Q9BXW4	Q9Y4P1	0	cleavage	up-regulates activity	0.757	Human atg4 homologues cleave the carboxyl termini of the three human atg8 homologues, microtubule-associated protein light chain 3 (lc3), gabarap, and gate-16.	SIGNOR-125489
P42681	Q13094	1	phosphorylation	up-regulates	0.728	Resting lymphocyte kinase (rlk/txk) targets lymphoid adaptor slp-76 in the cooperative activation of interleukin-2 transcription in t-cells. In this study, we report that rlk phosphorylates slp-76 at its n-terminal yesp/yepp sites. A third tyrosine within the amino-terminal region (y145) appears to be the most important for optimal slp-76 function	SIGNOR-44669
Q00535	Q96RR4	1	phosphorylation	down-regulates	0.2	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-198111
P17612	Q93045	1	phosphorylation	down-regulates activity	0.309	Using in vitro phosphorylated recombinant protein, four phosphorylation sites were identified in the SCG10 sequence. Ser-50 and Ser-97 were the target sites for protein kinase A. phosphorylation negatively regulates the microtubule-depolymerizing activity of SCG10 and that all four sites participate in this regulation	SIGNOR-250056
P60484	Q9UDY6	0	ubiquitination	down-regulates quantity	0.2	Collectively, these results indicate that TRIM10 may lead to ubiquitination and degradation of PTEN, which could be an underlying reason for AKT signalling inhibition in cardiac hypertrophy processes (Figure\u00a05D).4\n\nDISCUSSION.\|In addition, we found that the effect regulated by TRIM10 was mediated by interactions with phosphatase and tensin homolog (PTEN); specifically, TRIM10 promoted PTEN ubiquitination, thus leading to AKT signalling activation.\|The results showed that TRIM10 overexpression decreased PTEN expression, and MG132 reversed the reduction in PTEN (Figure\u00a05C).	SIGNOR-278729
Q9UBF6	P68400	0	phosphorylation	up-regulates	0.457	Ckbbp1 is phosphorylated in vivo and threonine to alanine mutation at residue 10 abrogates the phosphorylation of ckbbp1 observed in vivo, indicating that ckii is a major kinase that is responsible for in vivo phosphorylation of ckbbp1. As compared with the wild-type ckbbp1 or ckbbp1t10e (in which threonine 10 is replaced by glutamate), overexpression of nonphosphorylatable ckbbp1 (ckbbp1t10a) results in accumulation of ikappabalpha and p27kip1.	SIGNOR-101187
P08670	P31749	0	phosphorylation	up-regulates quantity by stabilization	0.647	The binding of akt (tail region) to vim (head region) results in vim ser39 phosphorylation enhancing the ability of vim to induce motility and invasion while protecting vim from caspase-induced proteolysis.	SIGNOR-252511
P49917	P78527	0	phosphorylation	down-regulates	0.808	Using tandem mass spectrometry, we identified a dna-pk phosphorylation site at thr-650 in human lig4 and a potential second phosphorylation site at ser-668 or ser-672. Phosphorylation of lig4 per se was not required for lig4 dna end joining activity. Substitution of these amino acids with alanine, individually or in combination, led to changes in lig4 protein stability of mouse lig4. The phosphomimetic mutation s650d returned lig4 stability to that of the wild-type protein. Furthermore dna-pk was found to negatively regulate lig4 protein stability.	SIGNOR-125877
O15379	P60510	0	dephosphorylation	down-regulates activity	0.379	Here we demonstrate that, in addition to protein-protein interactions with NCoR/SMRT, the activity of HDAC3 is regulated by both phosphorylation and dephosphorylation. A protein kinase CK2 phosphoacceptor site in the HDAC3 protein was identified at position Ser424, which is a nonconserved residue among the class I HDACs. Mutation of this residue was found to reduce deacetylase activity.\|Significantly, both overexpression and siRNA knock-down approaches, and analysis of cells devoid of PP4c, unequivocally show that HDAC3 activity is inversely proportional to the cellular abundance of PP4(c).	SIGNOR-248548
P18848	P07814	1	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269419
Q9HCE7	Q13950	1	ubiquitination	down-regulates activity	0.504	Recently we have found that smurf1 mediates the protein degradation of the osteoblast-specific transcription factor runx2/cbfa1.	SIGNOR-95233
P06493	O15287	1	phosphorylation	up-regulates	0.355	S387a mutant abolished fancg fusion protein phosphorylation by cdc2.	SIGNOR-129061
Q14493	Q16777	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-265398
Q16623	P53355	0	phosphorylation	down-regulates activity	0.339	Syntaxin-1A phosphorylation by DAP kinase or its S188D mutant, which mimics a state of complete phosphorylation, significantly decreases syntaxin binding to Munc18-1, a syntaxin-binding protein that regulates SNARE complex formation and is required for synaptic vesicle docking.	SIGNOR-251083
P61586	O60610	1	null	up-regulates activity	0.785	We find that the small GTPase Rho regulates R-cadherin adherens junction formation via Dia1 (also known as p140mDia) and profilin-1-mediated signaling pathway. The role played by Rho in regulating R-cadherin is underscored by the fact that constitutively active RhoA(Q63L) induces R-cadherin junction formation in MDA-MB-231 cells.\|Data presented thus far demonstrated that Rho, Dia1, and profilin-1 were required for R-cadherin junction formation in N480 cells.	SIGNOR-253108
Q9P1W9	Q16875	1	phosphorylation	up-regulates quantity by stabilization	0.2	We used biochemical methods to determine that PIM2 can directly bind and change the phosphorylation of PFKFB3 at Ser478 to enhance PFKFB3 protein stability through the ubiquitin-proteasome pathway.	SIGNOR-277554
P06493	P05787	1	phosphorylation	up-regulates	0.248	With regard to k8 phosphorylation at ser-431, it increases dramatically upon stimulation of cells with epidermal growth factor (egf) or after mitotic arrest and is the major k8 phosphorylated residue after incubating k8 immunoprecipitates with mitogen-activated protein or cdc2 kinases.	SIGNOR-56054
P53350	P30307	1	phosphorylation	up-regulates	0.804	The nuclear accumulation of active m-phase promoting factor (mpf) during prophase is thought to be essential for coordinating m-phase events in vertebrate cells. The protein phosphatase cdc25c, an activator of mpf, enters the nucleus to keep mpf active in the nucleus during prophase. these results suggest that plk1 phosphorylates cdc25c on ser198 and regulates nuclear translocation of cdc25c during prophase.	SIGNOR-115993
P23443	P67775	0	dephosphorylation	down-regulates	0.72	Protein phosphatase 2a inactivates the mitogen-stimulated s6 kinase from swiss mouse 3t3 cells	SIGNOR-23575
Q99743	P20393	0	transcriptional regulation	down-regulates quantity by repression	0.631	In this study, we found that NPAS2, like BMAL1, is a direct target gene of RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding.	SIGNOR-267981
P00519	Q14653	1	phosphorylation	up-regulates activity	0.2	The data in this study show that IRF3 is physically associated with c-Abl in vivo and directly binds to c-Abl in vitro. IRF3 is phosphorylated by c-Abl and c-Abl-related kinase, Arg, mainly at Y292.	SIGNOR-277440
P61978	Q05655	0	phosphorylation	down-regulates	0.344	Ser302 is a major k protein site phosphorylated by pkcdelta in vitrothe ability of pkc_ to inducibly bind and phosphorylate k protein may serve not only to alter the activity of k protein itself, but k protein may also provide an avenue for pkc_ to engage in a cross-talk with other k protein molecular partners in response to specific changes in the extracellular environment	SIGNOR-67515
O43896	Q9NRW1	1	relocalization	up-regulates quantity	0.2	Here, we identify Bicaudal-D-related protein 1 (BICDR-1) as an effector of the small GTPase Rab6 and key component of the molecular machinery that controls secretory vesicle transport in developing neurons. BICDR-1 interacts with kinesin motor Kif1C, the dynein/dynactin retrograde motor complex, regulates the pericentrosomal localization of Rab6-positive secretory vesicles and is required for neural development in zebrafish. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation.	SIGNOR-266878
Q96RR4	P49841	0	phosphorylation	down-regulates	0.272	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-198134
Q92997	Q9NQ66	1	null	up-regulates activity	0.347	Dsh through PLC activates IP3, which leads to release of intracellular Ca2+, which in turn activates CamK11 and calcineurin	SIGNOR-258980
O95260	P11021	1	post transcriptional regulation	down-regulates quantity by destabilization	0.295	We showed that the molecular chaperone BiP (also known as GRP78) was short-lived under basal conditions and ER stress. The turnover of BiP was in part driven by its amino-terminal arginylation (Nt-arginylation) by the arginyltransferase ATE1, which generated an autophagic N-degron of the N-end rule pathway.	SIGNOR-261345
P12931	P42681	1	phosphorylation	up-regulates activity	0.348	We further demonstrate that Rlk can be phosphorylated and activated by Src kinases, leading to a decrease in its half-life. A specific tyrosine in the activation loop of Rlk, Y420, is required for phosphorylation and activation, as well as for decreased stability, but is not required for lipid RAFT association.	SIGNOR-247346
P12931	O00401	1	phosphorylation	up-regulates activity	0.759	An Src family tyrosine kinase, v-Src, phosphorylates and activates N-WASP.	SIGNOR-279487
P43405	Q13261	1	phosphorylation	up-regulates activity	0.329	Mutation of a defined region of the intracellular signaling portion of IL-15Ralpha (Tyr227) abrogates both the IL-15Ralpha/Syk association and IL-15Ralpha phosphorylation. Taken together, this suggests that Syk kinase physically and functionally associates with the IL-15Ralpha chain in B cells and that Syk plays a key role in mediating IL-15-induced signal transduction, thus accounting for the distinct functional consequences of IL-15 vs IL-2 binding to B cells	SIGNOR-246556
Q96G74	Q13114	1	deubiquitination	down-regulates activity	0.775	TRAF3 is an E3 ubiquitin ligase that preferentially assembled lysine-63-linked polyubiquitin chains. DUBA selectively cleaved the lysine-63-linked polyubiquitin chains on TRAF3, resulting in its dissociation from the downstream signaling complex containing TANK-binding kinase 1.	SIGNOR-265873
O00548	P51608	0	transcriptional regulation	down-regulates quantity by repression	0.2	As the first step to reveal how MeCP2 phosphorylation may regulate Notch signaling, we conducted chromatin immunoprecipitation (ChIP) experiment to determine whether the phosphor-mutant MeCP2 protein has altered promoter occupancy at the promoters of Dll1 and Notch1. We found increased binding of the phosphor-mutant protein at the promoters of both Dll1 and Notch1	SIGNOR-264674
P10412	Q96GD4	0	phosphorylation	up-regulates quantity by stabilization	0.2	we showed previously that phosphorylation of S27 in human histone H1.4 (H1.4S27-P), prevents binding of heterochromatin protein 1 (HP1) family members (officially known as chromobox protein homologs) to the neighboring dimethylated K26. Here, we present the first functional characterization of H1.4S27-P in vivo and in vitro. We show that H1.4S27 phosphorylation is cell-cycle-regulated and its levels peak on metaphase chromosomes. We identify further Aurora B as the kinase phosphorylating H1.4S27.	SIGNOR-262658

P25963

Q9HC78

0

transcriptional regulation

down-regulates quantity by repression

0.259

ChIP and next generation high-throughput DNA sequencing assay showed that ZBTB20 specifically bound to IκBα gene promoter (+1 to +60 region) after TLR activation. ZBTB20 could inhibit IκBα gene transcription, govern IκBα protein expression, and then promote NF-κB activation. Therefore, transcriptional repressor ZBTB20 is needed to promote full activation of TLR signaling and TLR-triggered innate immune response by selectively suppressing the suppressor IκBα gene transcription.

SIGNOR-266868

P61586

Q02156

0

phosphorylation

up-regulates activity

0.439

Our laboratory reported that PKCepsilon modulates RhoA activity in HNSCC presumably through posttranslation phosphorylation .|Phosphopeptide mapping revealed that PKCepsilon phosphorylates RhoA at T127 and S188.

SIGNOR-279478

Q15561

P29279

1

transcriptional regulation

up-regulates quantity by expression

0.2

The multifunctional cytokine TGF-β has been identified as a potent inducer of CTGF expression, activating CTGF transcription through the canonical Smad signaling pathway. It is worth noting that TGF-β synergizes with Hippo–Yes-associated protein (YAP) signaling, a key regulator of tumorigenesis, to induce the expression of CTGF by the formation of a YAP-TEAD4-Smad3-p300 complex on the CTGF promoter

SIGNOR-277686

P53350

P67809

1

phosphorylation

up-regulates quantity

0.253

Here we identify that PLK1 inhibition can induce apoptosis and DNA damage of GSCs, we have also delineat the possible underlying molecular mechanisms: PLK1 interacts with YBX1 and directly phosphorylates serine 174 and serine 176 of YBX1.|Inhibition of PLK1 reduces the phosphorylation level of YBX1, and decreased phosphorylation of YBX1 prevents its nuclear translocation, thereby inducing apoptosis and DNA damage of GSCs.

SIGNOR-279255

Q9UQC2

O60674

0

phosphorylation

up-regulates

0.515

In vitro, activated jak2 directly phosphorylated specific gab2 tyrosine residues. Mutagenesis studies revealed that gab2 tyrosine 643 (y643) was a major target of jak2 in vitro, and a key residue for jak2-dependent phosphorylation in intact cells. Mutation of gab2 y643 inhibited g-csf-stimulated erk1/2 activation and shp2 binding to gab2.

SIGNOR-179488

P18507

Q02156

0

phosphorylation

down-regulates activity

0.233

Protein kinase C epsilon regulates gamma-aminobutyrate type A receptor sensitivity to ethanol and benzodiazepines through phosphorylation of gamma2 subunits. Our findings indicate that PKCepsilon phosphorylation of gamma2 regulates the response of GABA(A) receptors to specific allosteric modulators, and, in particular, PKCepsilon inhibition renders these receptors sensitive to low intoxicating concentrations of ethanol.

SIGNOR-263174

P17612

P24390

1

phosphorylation

up-regulates

0.309

We conclude that pka phosphorylation of serine 209 is required for the retrograde transport of the kdel receptor from the golgi complex to the er from which the retrieval of proteins bearing the kdel signal depends.

SIGNOR-118257

Q12791

P17252

0

phosphorylation

up-regulates

0.2

Results showed that mutating s1076 altered the effect of pkc activation on bk(ca) channels in hek-293 cells

SIGNOR-186755

P17612

Q01082

1

phosphorylation

down-regulates activity

0.331

Short C-terminal splice variant of betaII-spectrin (betaIISigma2) is a substrate for phosphorylation. protein kinase A phosphorylates Thr-2159. Mammalian alphaII- and betaII-spectrin subunits form dimers that associate head to head with high affinity to form tetramers In vitro, protein kinase A phosphorylation of an active fragment of betaIISigma2 greatly reduced its interaction with alphaII-spectrin at the tetramerization site.

SIGNOR-250054

P23025

O95714

0

ubiquitination

down-regulates

0.385

Herc2 may ubiquitinate xpa and thus target it for proteolytic degradation

SIGNOR-164595

Q13698

P67870

0

phosphorylation

up-regulates activity

0.2

To identify the regulatory sites of phosphorylation under physiologically relevant conditions, Ca(V)1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac Ca(V)1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that Ca(V)1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas Ca(V)1.1-T1579 is a substrate for casein kinase 2.

SIGNOR-263115

O43819

P04637

0

transcriptional regulation

up-regulates quantity by expression

0.64

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

SIGNOR-267463

O43684

Q13315

0

phosphorylation

up-regulates activity

0.312

Taken together, we highlight the functional significance of the crosstalk between the kinetochore-oriented signal and double-strand break repair pathways via ATM phosphorylation of Bub3 on Ser135.

SIGNOR-277582

P14091

P01023

1

cleavage

down-regulates quantity by destabilization

0.38

Disruption of structural and functional integrity of alpha 2-macroglobulin by cathepsin E|Analysis of the N-terminal amino-acid sequences of these proteins revealed that alpha 2M was selectively cleaved at the Phe811-Leu812 bond in about 100mer downstream of the bait region.

SIGNOR-266977

P30530

Q63HR2

1

phosphorylation

up-regulates quantity

0.2

In this study, however, we demonstrate for the first time that Axl directly binds to and phosphorylates TNS2 at Y483.|Overall these results suggest that Axl positively regulates TNS2 expression.

SIGNOR-278471

Q12955

O94856

0

relocalization

up-regulates quantity

0.745

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

SIGNOR-266717

P06493

P19525

0

phosphorylation

down-regulates

0.328

Our findings demonstrate that (i) pkr, ser/thr kinase, phosphorylates its new substrate cdc2 at the tyr 4 residue, (ii) pkr-mediated tyr 4-phosphorylation facilitates cdc2 ubiquitination and proteosomal degradation

SIGNOR-164809

Q92769

P67775

0

dephosphorylation

down-regulates activity

0.281

In contrast, in the present work, PPP2CA reduced HDAC2 S394 phosphorylation.|We postulated that PPP2CA would negatively regulate phospho dependent HDAC2 activity.

SIGNOR-277049

Q9BY41

P04637

1

deacetylation

down-regulates activity

0.456

HDAC8 mediates CM-induced deacetylation of p53.Collectively, these results indicate that although binding to p53 and HDAC8 occurs through distinct regions of the CM protein, simultaneous interaction with HDAC8 and p53 is required for aberrant deacetylation and inactivation of p53.

SIGNOR-255738

Q13541

P19784

0

phosphorylation

down-regulates activity

0.333

The kinase is quite distinct from casein kinase 2, which also phosphorylates Ser-111 of 4E-BP1. The possible importance of these kinases in the phosphorylation of 4E-BP1 in fat cells is discussed. It is suggested that the phosphorylation of Ser-111 might be a priming event that facilitates the subsequent phosphorylation of Thr-36, Thr-45, Ser-64 and Thr69 by a rapamycin-sensitive process that initiates the dissociation of 4E-BP1 from eIF4E and hence the formation of the eIF4F complex.

SIGNOR-249334

Q13315

P54646

1

phosphorylation

up-regulates activity

0.264

ATM phosphorylates AMPKalpha2 to induce inhibitory phosphorylation of HIPK2|

SIGNOR-275488

Q9BYF1

P01019

1

cleavage

up-regulates activity

0.759

The ACE2 hydrolytic activity is dependent on the C terminus sequence of the substrate, which is evident from the data with the angiotensin peptides. After 2 h, ACE2 hydrolyzes Ang I partially and Ang II completely, although there is no hydrolysis of angiotensin 1–9, angiotensin 1–7, and angiotensin 1–5, which possess the same N terminus.

SIGNOR-256315

P40692

P00519

0

phosphorylation

up-regulates quantity by stabilization

0.344

We also observed phosphorylation of MLH1 by ABL1 in an in vitro kinase assay with purified recombinant ABL1 and MLH1, confirming there is a direct phosphorylation between ABL1 and the MLH1 component of the MLH1-PMS2 heterodimer.|we propose that ABL1 prevents MLH1 from being targeted for degradation by the chaperone Hsp70 and that in the absence of ABL1 activity at least a portion of MLH1 is degraded.

SIGNOR-279581

Q13535

P16104

1

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

P35712

P63279

0

sumoylation

down-regulates activity

0.367

We show that SOX6 is modified in vitro and in vivo by small ubiquitin‐related modifier (SUMO) on two distinct sites. Mutation of both sites abolished SOX6 sumoylation and increased SOX6 transcriptional activity. SUMO dependent repression of SOX6 transcription was promoted by UBC9 whereas siRNA to UBC9, cotransfection of inactive UBC9 or a SUMO protease increased SOX6 transcriptional activity.

SIGNOR-256130

Q99728

P24941

0

phosphorylation

down-regulates activity

0.609

CDK2-cyclin A1/E1 and CDK1-cyclin B1 phosphorylate BARD1 on its NH(2) terminus in vivo and in vitro. 44999999="E1" 45999998="terminus"}|Here we show that the ubiquitin ligase activity of BRCA1-BARD1 is down-regulated by CDK2.

SIGNOR-280211

Q06187

P78347

1

phosphorylation

up-regulates activity

0.517

These residues, tyr248, tyr357, and tyr462, were also found to be the major sites for btk-dependent phosphorylation of bap/tfii-i in vivo. Residues tyr357 and tyr462 are contained within the loop regions of adjacent helix-loop-helix-like repeats within bap/tfii-i. Mutation of either tyr248, tyr357, or tyr462 to phenylalanine reduced transcription from a c-fos promoter relative to wild-type bap/tfii-i in transfected cos-7 cells, consistent with the interpretation that phosphorylation at these sites contributes to transcriptional activation.

SIGNOR-108346

Q92911

P27695

0

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

Q9Y618

P06401

1

acetylation

down-regulates

0.588

In this study we assessed the effect of smrt and dax-1 on ar and pr activity in the presence of both agonists and partial antagonists. We show that smrt and dax-1 repress agonist-dependent activity of both receptors, and the mechanism of repression includes disruption of the receptor dimer interactions rather than recruitment of histone deacetylases.

SIGNOR-101289

Q9H1B7

P01210

1

transcriptional regulation

down-regulates quantity by repression

0.307

EAP1 encoded a nuclear protein expressed in neurons involved in the inhibitory and facilitatory control of reproduction. EAP1 transactivated genes required for reproductive function, such as GNRH1, and repressed inhibitory genes, such as preproenkephalin. It contained a RING finger domain of the C3HC4 subclass required for this dual transcriptional activity.These results suggest that EAP1 is a transcriptional regulator that, acting within the neuroendocrine brain, contributes to controlling female reproductive function.

SIGNOR-267155

P53779

P04637

1

phosphorylation

up-regulates

0.628

The targets of jnk include the transcription factors p53. P75ntr-mediated apoptosis was shown to be dependent of p53

SIGNOR-120552

P47712

O75582

0

phosphorylation

up-regulates activity

0.352

Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases.

SIGNOR-249051

P19174

P16234

0

phosphorylation

up-regulates

0.65

Tyrosine phosphorylation has been shown to increase the enzymatic activity of plc-? / we show that the human pdgf ?- And ?-Receptors differ quantitatively in their abilities to associate with and phosphorylate plc-? And to stimulate inositol phosphate production.

SIGNOR-28176

Q05655

P35236

1

phosphorylation

up-regulates activity

0.2

HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.

SIGNOR-276048

O14672

P22415

0

transcriptional regulation

up-regulates quantity by expression

0.27

The promoter region of ADAM10 contains several transcription factor binding sites that can stimulate its transcription. These include binding sites for transcription factors SP1 and USF, and the spliced form of the X-box binding protein (XBP)-1 as well as a retinoic acid-responsive element

SIGNOR-259837

P04070

P38435

0

carboxylation

up-regulates activity

0.572

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-265925

Q9UMX1

P51955

0

phosphorylation

up-regulates activity

0.2

Intriguingly, Nek2A is found to stabilize SuFu at least partly depending on its kinase activity, thereby triggering phosphorylation of the SuFu protein.|Nek2A phosphorylates and stabilizes SuFu: A new strategy of Gli2/Hedgehog signaling regulatory mechanism.

SIGNOR-279235

P04637

Q15831

0

phosphorylation

up-regulates

0.756

We show that lkb1 physically associates with p53 in the nucleus and directly or indirectly phosphorylates p53 ser15 (previously shown to be phosphorylated by amp-dependent kinase) and p53 ser392

SIGNOR-150830

P49841

P98170

1

phosphorylation

up-regulates activity

0.394

We now demonstrate that XIAP is phosphorylated by GSK3 at threonine 180, and that an alanine mutant (XIAPT180A) exhibits decreased Wnt activity compared to wild-type XIAP in cultured human cells and in Xenopus embryos.

SIGNOR-277390

Q68DV7

P04637

1

ubiquitination

down-regulates quantity by destabilization

0.451

Moreover, RNF43 polyubiquitinates p53 which further leads to its destabilization resulting in a decrease in induction of the p53 apoptotic pathway, a hitherto unknown process targeted by NP for p53 stabilization and accumulation.

SIGNOR-278714

P36888

P48735

1

phosphorylation

down-regulates activity

0.421

FLT3 promotes mIDH2 acetylation through Y107 phosphorylation of mIDH2 that enhances ACAT1 recruitment,

SIGNOR-267632

P31749

P62140

0

dephosphorylation

down-regulates activity

0.386

Here, we identify PP1 as a serine/threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells|The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells

SIGNOR-252604

P48431

P24941

0

phosphorylation

up-regulates activity

0.394

Cdk2 physically interacts with Sox2 and phosphorylates Sox2 at Ser 39 and Ser 253 in vitro.

SIGNOR-279448

P10586

P19174

1

dephosphorylation

down-regulates

0.2

Here we show that lar reduces the constitutive tyrosine autophosphorylation and kinase activity of ret-men2a but not ret-men2b, accompanying a significant decrease of phosphorylation of phospholipase cgamma, akt, and erk1/2.

SIGNOR-85166

P0DP91

P00519

0

phosphorylation

up-regulates activity

0.271

These data raise the possibility that tyrosine phosphorylation of CSB by c-Abl promotes redistribution of CSB in the nucleus and enrichment of CSB in the nucleolus in response to oxidative stress

SIGNOR-279317

P84243

O14757

0

phosphorylation

down-regulates activity

0.2

We identify chk1 as the kinase responsible for h3-t11 phosphorylation. H3-t11 phosphorylation occurs throughout the cell cycle and is chk1 dependent in vivo.Phosphorylation at thr-12 (h3t11ph) by pkn1 is a specific tag for epigenetic transcriptional activation that promotes demethylation of lys-10 (h3k9me) by kdm4c/jmjd2c.

SIGNOR-160557

P28482

Q9UKX7

1

phosphorylation

down-regulates activity

0.2

Erk phosphorylates nup50 at ser221 and ser315 erk phosphorylation of the fg repeat region of nup50 reduced its affinity for importin-beta family proteins, importin-beta and transportin.

SIGNOR-188135

P30281

Q15759

0

phosphorylation

down-regulates quantity by destabilization

0.2

P38SAPK2 phosphorylates cyclin D3 at Thr-283 and targets it for proteasomal degradation.

SIGNOR-280023

P04637

P67775

0

dephosphorylation

down-regulates activity

0.59

Phosphorylation of p53 at serine 37 is important for transcriptional activity and regulation in response to DNA damage| Furthermore, in vitro phosphatase assays show that PP2A dephosphorylates p53 at S37.

SIGNOR-248619

P45983

P16104

1

phosphorylation

up-regulates

0.2

The stress-response kinase jnk1, activated by dna damage and initiating a pro-apoptotic program, has been recently shown to translocate into the nucleus upon activation where it phosphorylates substrates including h2ax s139, an event critical for dna degradation mediated by caspase-activated dnase (cad) in apoptotic cells

SIGNOR-184146

Q9NRM7

P00519

1

phosphorylation

down-regulates activity

0.362

Inhibition of c-Abl by Lats2 was mediated through Lats2 interaction with and phosphorylation of c-Abl. Lats2 phosphorylates c-Abl at Thr197 in vitro.

SIGNOR-276497

P61586

O94989

0

guanine nucleotide exchange factor

up-regulates activity

0.571

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-260540

P11137

Q76NI1

0

phosphorylation

up-regulates activity

0.369

V-KIND enhances Thr phosphorylation of MAP2.

SIGNOR-278950

P78536

P07359

1

cleavage

down-regulates activity

0.284

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

SIGNOR-261861

O00141

Q969H0

1

phosphorylation

up-regulates

0.291

Here, we report that the serum- and glucocorticoid-inducible protein kinase sgk1 remarkably reduced the protein stability of the active form of notch1 through fbw7activated sgk1 phosphorylated fbw7 at serine 227

SIGNOR-170404

P06241

P52757

1

phosphorylation

down-regulates

0.2

Ere we report that beta2-chimaerin is tyrosine-phosphorylated by src-family kinases (sfks) upon cell stimulation with epidermal growth factor (egf). these results suggest tyr-21 phosphorylation as a novel, sfk-dependent mechanism that negatively regulates beta2-chimaerin rac-gap activity.

SIGNOR-155709

Q03112

Q13315

0

phosphorylation

up-regulates activity

0.2

To investigate to what extent EVI1 function might be regulated by post-translational modifications we carried out mass spectrometry- and antibody-based analyses and uncovered an ATM-mediated double phosphorylation of EVI1 at the carboxy-terminal S858/S860 SQS motif.

SIGNOR-273433

P68431

P51812

0

phosphorylation

down-regulates activity

0.2

Phosphorylation at ser-11 (h3s10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or uv irradiation and result in the activation of genes, such as c-fos and c-jun.

SIGNOR-119229

P17302

P78415

0

transcriptional regulation

down-regulates quantity by repression

0.278

Irx3 directly represses Cx43 transcription

SIGNOR-266044

P30530

P07947

1

phosphorylation

up-regulates activity

0.2

Here, we show that EphA2, YES1, and ANXA2 form a signal axis, in which YES1 activated by EphA2 phosphorylates ANXA2 at Tyr24 site, leading to ANXA2 activation and increased ANXA2 nuclear distribution in gastric cancer (GC) cells.

SIGNOR-277555

Q8N5B7

P68400

0

phosphorylation

up-regulates activity

0.2

Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue.

SIGNOR-273987

Q13887

Q05655

0

phosphorylation

up-regulates activity

0.335

Phosphorylation of Kruppel-like factor 5 (KLF5/IKLF) at the CBP interaction region enhances its transactivation function. | Inhibition of protein kinase activity by H7 or calphostin C blocked both full-length and N-terminal fragment (amino acids 1-238) KLF5 activities. Mutation at a potential protein kinase C phosphorylation site within the CBP interaction domain of KLF5 reduces its transactivation function. Furthermore, using the GST pull-down approach, we showed that phosphorylation of KLF5 enhances its interaction with CBP. The results of the present study provide a mechanism for KLF5 transactivation function. | We found that KLF5s activity was reduced to half when the serine in the potential PKC phosphorylation site was mutated to alanine (Fig. 6B, S153A) Nonetheless, the S153A mutant still retains significant transactivation activity.

SIGNOR-249206

P42224

Q05655

0

phosphorylation

up-regulates

0.589

All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below).

SIGNOR-154791

Q9NZC9

Q13535

0

phosphorylation

down-regulates activity

0.538

ATR phosphorylates SMARCAL1 on S652, thereby limiting its fork regression activities and preventing aberrant fork processing. Thus, phosphorylation of SMARCAL1 is one mechanism by which ATR prevents fork collapse, promotes the completion of DNA replication, and maintains genome integrity.

SIGNOR-273516

Q13043

O95835

1

phosphorylation

up-regulates

0.623

We show that Mst2 and hWW45 interact with each other in human cells and that both Mst2 and Mst1 are able to phosphorylate Lats1 and Lats2, thereby stimulating Lats kinase activity.

SIGNOR-133551

P49137

Q6JBY9

1

phosphorylation

down-regulates activity

0.477

Human CapZIP was phosphorylated at Ser-179 and Ser-244 by MAPKAP-K2 (mitogen-activated protein kinase-activated protein kinase 2) or MAPKAP-K3 in vitro. In the present paper we have identified CapZIP as a protein that is phosphorylated exceptionally rapidly by several SAPKs in vitro (Figure 4), and which is expressed in muscles and immune cells. Both MAPKAP-K2 and MAPKAP-K3 phosphorylated CapZIP at Ser-179 in vitro. An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.

SIGNOR-263080

Q9BV68

P00533

1

polyubiquitination

down-regulates quantity by destabilization

0.328

RNF126 and Rabring7 associate with the EGFR through a ubiquitin-binding zinc finger domain and both E3 ubiquitin ligases promote ubiquitylation of EGFR. In HeLa cells depleted of either RNF126 or Rabring7 the EGFR is retained in a late endocytic compartment and is inefficiently degraded.

SIGNOR-272103

Q9BXW9

P68400

0

phosphorylation

down-regulates activity

0.2

Here, we report a cluster of phosphosites on FANCD2 whose phosphorylation by CK2 inhibits both FANCD2 recruitment to ICLs and its monoubiquitination in vitro and in vivo. We have found that phosphorylated FANCD2 possesses reduced DNA binding activity, explaining the previous observations.

SIGNOR-276730

Q9BXW4

Q9Y4P1

0

cleavage

up-regulates activity

0.757

Human atg4 homologues cleave the carboxyl termini of the three human atg8 homologues, microtubule-associated protein light chain 3 (lc3), gabarap, and gate-16.

SIGNOR-125489

P42681

Q13094

1

phosphorylation

up-regulates

0.728

Resting lymphocyte kinase (rlk/txk) targets lymphoid adaptor slp-76 in the cooperative activation of interleukin-2 transcription in t-cells. In this study, we report that rlk phosphorylates slp-76 at its n-terminal yesp/yepp sites. A third tyrosine within the amino-terminal region (y145) appears to be the most important for optimal slp-76 function

SIGNOR-44669

Q00535

Q96RR4

1

phosphorylation

down-regulates

0.2

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-198111

P17612

Q93045

1

phosphorylation

down-regulates activity

0.309

Using in vitro phosphorylated recombinant protein, four phosphorylation sites were identified in the SCG10 sequence. Ser-50 and Ser-97 were the target sites for protein kinase A. phosphorylation negatively regulates the microtubule-depolymerizing activity of SCG10 and that all four sites participate in this regulation

SIGNOR-250056

P60484

Q9UDY6

0

ubiquitination

down-regulates quantity

0.2

Collectively, these results indicate that TRIM10 may lead to ubiquitination and degradation of PTEN, which could be an underlying reason for AKT signalling inhibition in cardiac hypertrophy processes (Figure\u00a05D).4\n\nDISCUSSION.|In addition, we found that the effect regulated by TRIM10 was mediated by interactions with phosphatase and tensin homolog (PTEN); specifically, TRIM10 promoted PTEN ubiquitination, thus leading to AKT signalling activation.|The results showed that TRIM10 overexpression decreased PTEN expression, and MG132 reversed the reduction in PTEN (Figure\u00a05C).

SIGNOR-278729

Q9UBF6

P68400

0

phosphorylation

up-regulates

0.457

Ckbbp1 is phosphorylated in vivo and threonine to alanine mutation at residue 10 abrogates the phosphorylation of ckbbp1 observed in vivo, indicating that ckii is a major kinase that is responsible for in vivo phosphorylation of ckbbp1. As compared with the wild-type ckbbp1 or ckbbp1t10e (in which threonine 10 is replaced by glutamate), overexpression of nonphosphorylatable ckbbp1 (ckbbp1t10a) results in accumulation of ikappabalpha and p27kip1.

SIGNOR-101187

P08670

P31749

0

phosphorylation

up-regulates quantity by stabilization

0.647

The binding of akt (tail region) to vim (head region) results in vim ser39 phosphorylation enhancing the ability of vim to induce motility and invasion while protecting vim from caspase-induced proteolysis.

SIGNOR-252511

P49917

P78527

0

phosphorylation

down-regulates

0.808

Using tandem mass spectrometry, we identified a dna-pk phosphorylation site at thr-650 in human lig4 and a potential second phosphorylation site at ser-668 or ser-672. Phosphorylation of lig4 per se was not required for lig4 dna end joining activity. Substitution of these amino acids with alanine, individually or in combination, led to changes in lig4 protein stability of mouse lig4. The phosphomimetic mutation s650d returned lig4 stability to that of the wild-type protein. Furthermore dna-pk was found to negatively regulate lig4 protein stability.

SIGNOR-125877

O15379

P60510

0

dephosphorylation

down-regulates activity

0.379

Here we demonstrate that, in addition to protein-protein interactions with NCoR/SMRT, the activity of HDAC3 is regulated by both phosphorylation and dephosphorylation. A protein kinase CK2 phosphoacceptor site in the HDAC3 protein was identified at position Ser424, which is a nonconserved residue among the class I HDACs. Mutation of this residue was found to reduce deacetylase activity.|Significantly, both overexpression and siRNA knock-down approaches, and analysis of cells devoid of PP4c, unequivocally show that HDAC3 activity is inversely proportional to the cellular abundance of PP4(c).

SIGNOR-248548

P18848

P07814

1

transcriptional regulation

up-regulates quantity by expression

0.2

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269419

Q9HCE7

Q13950

1

ubiquitination

down-regulates activity

0.504

Recently we have found that smurf1 mediates the protein degradation of the osteoblast-specific transcription factor runx2/cbfa1.

SIGNOR-95233

P06493

O15287

1

phosphorylation

up-regulates

0.355

S387a mutant abolished fancg fusion protein phosphorylation by cdc2.

SIGNOR-129061

Q14493

Q16777

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-265398

Q16623

P53355

0

phosphorylation

down-regulates activity

0.339

Syntaxin-1A phosphorylation by DAP kinase or its S188D mutant, which mimics a state of complete phosphorylation, significantly decreases syntaxin binding to Munc18-1, a syntaxin-binding protein that regulates SNARE complex formation and is required for synaptic vesicle docking.

SIGNOR-251083

P61586

O60610

1

null

up-regulates activity

0.785

We find that the small GTPase Rho regulates R-cadherin adherens junction formation via Dia1 (also known as p140mDia) and profilin-1-mediated signaling pathway. The role played by Rho in regulating R-cadherin is underscored by the fact that constitutively active RhoA(Q63L) induces R-cadherin junction formation in MDA-MB-231 cells.|Data presented thus far demonstrated that Rho, Dia1, and profilin-1 were required for R-cadherin junction formation in N480 cells.

SIGNOR-253108

Q9P1W9

Q16875

1

phosphorylation

up-regulates quantity by stabilization

0.2

We used biochemical methods to determine that PIM2 can directly bind and change the phosphorylation of PFKFB3 at Ser478 to enhance PFKFB3 protein stability through the ubiquitin-proteasome pathway.

SIGNOR-277554

P06493

P05787

1

phosphorylation

up-regulates

0.248

With regard to k8 phosphorylation at ser-431, it increases dramatically upon stimulation of cells with epidermal growth factor (egf) or after mitotic arrest and is the major k8 phosphorylated residue after incubating k8 immunoprecipitates with mitogen-activated protein or cdc2 kinases.

SIGNOR-56054

P53350

P30307

1

phosphorylation

up-regulates

0.804

The nuclear accumulation of active m-phase promoting factor (mpf) during prophase is thought to be essential for coordinating m-phase events in vertebrate cells. The protein phosphatase cdc25c, an activator of mpf, enters the nucleus to keep mpf active in the nucleus during prophase. these results suggest that plk1 phosphorylates cdc25c on ser198 and regulates nuclear translocation of cdc25c during prophase.

SIGNOR-115993

P23443

P67775

0

dephosphorylation

down-regulates

0.72

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

SIGNOR-23575

Q99743

P20393

0

transcriptional regulation

down-regulates quantity by repression

0.631

In this study, we found that NPAS2, like BMAL1, is a direct target gene of RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding.

SIGNOR-267981

P00519

Q14653

1

phosphorylation

up-regulates activity

0.2

The data in this study show that IRF3 is physically associated with c-Abl in vivo and directly binds to c-Abl in vitro. IRF3 is phosphorylated by c-Abl and c-Abl-related kinase, Arg, mainly at Y292.

SIGNOR-277440

P61978

Q05655

0

phosphorylation

down-regulates

0.344

Ser302 is a major k protein site phosphorylated by pkcdelta in vitrothe ability of pkc_ to inducibly bind and phosphorylate k protein may serve not only to alter the activity of k protein itself, but k protein may also provide an avenue for pkc_ to engage in a cross-talk with other k protein molecular partners in response to specific changes in the extracellular environment

SIGNOR-67515

O43896

Q9NRW1

1

relocalization

up-regulates quantity

0.2

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

SIGNOR-266878

Q96RR4

P49841

0

phosphorylation

down-regulates

0.272

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-198134

Q92997

Q9NQ66

1

null

up-regulates activity

0.347

Dsh through PLC activates IP3, which leads to release of intracellular Ca2+, which in turn activates CamK11 and calcineurin

SIGNOR-258980

O95260

P11021

1

post transcriptional regulation

down-regulates quantity by destabilization

0.295

We showed that the molecular chaperone BiP (also known as GRP78) was short-lived under basal conditions and ER stress. The turnover of BiP was in part driven by its amino-terminal arginylation (Nt-arginylation) by the arginyltransferase ATE1, which generated an autophagic N-degron of the N-end rule pathway.

SIGNOR-261345

P12931

P42681

1

phosphorylation

up-regulates activity

0.348

We further demonstrate that Rlk can be phosphorylated and activated by Src kinases, leading to a decrease in its half-life. A specific tyrosine in the activation loop of Rlk, Y420, is required for phosphorylation and activation, as well as for decreased stability, but is not required for lipid RAFT association.

SIGNOR-247346

P12931

O00401

1

phosphorylation

up-regulates activity

0.759

An Src family tyrosine kinase, v-Src, phosphorylates and activates N-WASP.

SIGNOR-279487

P43405

Q13261

1

phosphorylation

up-regulates activity

0.329

Mutation of a defined region of the intracellular signaling portion of IL-15Ralpha (Tyr227) abrogates both the IL-15Ralpha/Syk association and IL-15Ralpha phosphorylation. Taken together, this suggests that Syk kinase physically and functionally associates with the IL-15Ralpha chain in B cells and that Syk plays a key role in mediating IL-15-induced signal transduction, thus accounting for the distinct functional consequences of IL-15 vs IL-2 binding to B cells

SIGNOR-246556

Q96G74

Q13114

1

deubiquitination

down-regulates activity

0.775

TRAF3 is an E3 ubiquitin ligase that preferentially assembled lysine-63-linked polyubiquitin chains. DUBA selectively cleaved the lysine-63-linked polyubiquitin chains on TRAF3, resulting in its dissociation from the downstream signaling complex containing TANK-binding kinase 1.

SIGNOR-265873

O00548

P51608

0

transcriptional regulation

down-regulates quantity by repression

0.2

As the first step to reveal how MeCP2 phosphorylation may regulate Notch signaling, we conducted chromatin immunoprecipitation (ChIP) experiment to determine whether the phosphor-mutant MeCP2 protein has altered promoter occupancy at the promoters of Dll1 and Notch1. We found increased binding of the phosphor-mutant protein at the promoters of both Dll1 and Notch1

SIGNOR-264674

P10412

Q96GD4

0

phosphorylation

up-regulates quantity by stabilization

0.2

we showed previously that phosphorylation of S27 in human histone H1.4 (H1.4S27-P), prevents binding of heterochromatin protein 1 (HP1) family members (officially known as chromobox protein homologs) to the neighboring dimethylated K26. Here, we present the first functional characterization of H1.4S27-P in vivo and in vitro. We show that H1.4S27 phosphorylation is cell-cycle-regulated and its levels peak on metaphase chromosomes. We identify further Aurora B as the kinase phosphorylating H1.4S27.

SIGNOR-262658