GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q92858	O60674	phosphorylation	up-regulates quantity	0.339	We discovered tyrosine 78 of Atoh1 is phosphorylated by a Jak2-mediated pathway only in tumor-initiating cells and in human SHH-type medulloblastoma. Phosphorylation of tyrosine 78 stabilizes Atoh1, increases Atoh1’s transcriptional activity, and is independent of canonical Jak2 signaling.	SIGNOR-262201
P06127	P17252	phosphorylation	up-regulates	0.339	Cd5 is a good pkc substrate. Phosphorylation of cd5 is necessary for cd5-mediated lipid second messenger generation.	SIGNOR-85179
P29590	P27361	phosphorylation	up-regulates	0.339	Phosphorylation of pml by mitogen-activated protein kinases plays a key role in arsenic trioxide-mediated apoptosis.	SIGNOR-124317
P10915	P08253	cleavage	down-regulates quantity by destabilization	0.339	Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix.	SIGNOR-256333
P61978	P53779	phosphorylation	up-regulates activity	0.339	JNK Phosphorylation of HnRNP K Increases Its Transcriptional Activity. the primary site for JNK phosphorylation consists of serines 216 and 353 on the K protein.	SIGNOR-250083
P78344	P06493	phosphorylation	up-regulates activity	0.339	To test whether CDK1 phosphorylates T508, Flag-DAP5 was purified from dox-induced HEK293 cells and incubated with active recombinant JNK2 or CDK1 in the presence of ATP (Fig. 3G). DAP5(T508) was phosphorylated only upon incubation with CDK1 (Fig. 3G).	SIGNOR-266387
Q9BXM7	O75439	cleavage	down-regulates quantity by destabilization	0.339	Using an unbiased RNA-mediated interference (RNAi)-based screen, we identified four mitochondrial proteases, mitochondrial processing peptidase (MPP), presenilin-associated rhomboid-like protease (PARL), m-AAA and ClpXP, involved in PINK1 degradation. We find that PINK1 turnover is particularly sensitive to even modest reductions in MPP levels. Moreover, PINK1 cleavage by MPP is coupled to import such that reducing MPP activity induces PINK1 accumulation at the mitochondrial surface, leading to Parkin recruitment and mitophagy.	SIGNOR-261363
Q9NX09	P49841	phosphorylation	down-regulates quantity by destabilization	0.339	It has been reported that GSK3beta phosphorylates REDD1 at residues Thr23 and Thr25, resulting in REDD1 recruitment to the Cullin 4a-beta-Trcp E3 ligase complex.	SIGNOR-279526
Q9UPP1	Q12834	binding	down-regulates quantity by destabilization	0.339	We showed that PHF8 interacts with the CDC20-containing APC (APC(cdc20)) primarily during mitosis. we demonstrate that mutations of the LXPKXLF motif abrogate polyubiquitylation of PHF8 by the APC. APC substrates are typically cell cycle regulators, and consistent with this, the loss of PHF8 leads to prolonged G2 phase and defective mitosis.	SIGNOR-272879
Q16623	P53355	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
P27707	P48730	phosphorylation	up-regulates activity	0.339	Site-directed mutagenesis demonstrated that only Ser-74 phosphorylation was involved in Deoxycytidine kinase activation by CKI delta, strengthening the key role of this residue in the control of Deoxycytidine kinase activity.\|We showed that recombinant CKI delta phosphorylated several residues of bacterially overexpressed Deoxycytidine kinase: Ser-74, but also Ser-11, Ser-15, and Thr-72.	SIGNOR-280233
O75164	Q8NEZ5	ubiquitination	down-regulates quantity by destabilization	0.339	SCF(FBXO22) regulates histone H3 lysine 9 and 36 methylation levels by targeting histone demethylase KDM4A for ubiquitin-mediated proteasomal degradation	SIGNOR-273442
P56945	P10586	dephosphorylation	down-regulates quantity by destabilization	0.339	LAR specifically dephosphorylates and destabilizes p130Cas and may play a role in regulating cell adhesion-mediated cell survival.\|Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130Cas.	SIGNOR-276998
P25440	Q96DB2	binding	down-regulates activity	0.339	Ex vivo and cell-based assays revealed that HDAC11 catalytic activity suppresses the BAT transcriptional program, in both the basal state and in response to β-adrenergic receptor signaling, through a mechanism that is dependent on physical association with BRD2, a bromodomain and extraterminal (BET) acetyl-histone-binding protein.	SIGNOR-262058
P35568	P19525	phosphorylation	down-regulates activity	0.339	First, PKR induces phosphorylation of IRS1 at Ser312 and suppresses tyrosine phosphorylation of IRS1, mediated by the insulin receptor substrates kinases, JNK and I\u03baB kinase.\|These results suggest that PKR induces the inhibitory phosphorylation of IRS1 at Ser312 in HepG2 cells, thereby suppressing the phosphorylation at Tyr941.	SIGNOR-278310
O43603	Q9BT56	binding	up-regulates activity	0.339	Coevolution of the spexin/galanin/kisspeptin family: Spexin activates galanin receptor type II and III.	SIGNOR-268574
Q14315	P17252	phosphorylation	up-regulates quantity by stabilization	0.338	We identified the extended basophilic phosphosite motif RxRxxp[S/T]xxp[S/T] in various proteins including filamin-C (FLNc). Importantly, this extended motif, located in a unique insert in Ig-like domain 20 of FLNc, is doubly phosphorylated. The protein kinases responsible for this dual-site phosphorylation are Akt and PKCα. Proximity proteomics and interaction analysis identified filamin A-interacting protein 1 (FILIP1) as direct FLNc binding partner. FILIP1 binding induces filamin degradation, thereby negatively regulating its function. Here, dual-site phosphorylation of FLNc not only reduces FILIP1 binding, providing a mechanism to shield FLNc from FILIP1-mediated degradation, but also enables fast dynamics of FLNc necessary for its function as signaling adaptor in cross-striated muscle cells. In vitro kinase assays combined with LC-MS confirmed hFLNc-S2233 as a substrate of Akt, whereas PKCα preferentially targeted S2236.	SIGNOR-262617
Q8NEG5	P51965	binding	up-regulates activity	0.338	MEX can act as an E3, Ub (ubiquitin) ligase, through the E2, Ub-conjugating enzymes UbcH5a, UbcH5c or UbcH6. A region of MEX that contains the RING fingers and the ZZ zinc finger was required for interaction with UbcH5a and MEX self-association, whereas the SWIM domain was critical for MEX ubiquitination. The expression of MEX promoted apoptosis that was induced through Fas, DR (death receptor) 3 and DR4 signalling, but not that mediated by the BH3 (Bcl-2 homology 3)-only protein BimEL or the chemotherapeutic drug adriamycin.	SIGNOR-271555
P31947	P45983	phosphorylation	down-regulates	0.338	Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-187.	SIGNOR-124016
O95786	Q13283	binding	down-regulates activity	0.338	G3BP1 binds RIG-I and that this interaction involves the C-terminal RGG domain of G3BP1, G3BP1 significantly enhances RIG-I-induced ifn-b mRNA synthesis.	SIGNOR-260980
O00141	Q9HC98	phosphorylation	up-regulates activity	0.338	The present study is the first report of a protein kinase (NEK6) capable of phosphorylating the hydrophobic motif of SGK1, although our data suggest that NEK6 may not mediate this reaction in cells. Nevertheless, the phosphorylation of the hydrophobic motif of SGK1in vitro, coupled with the phosphorylation of the T-loop with PDK1, may be a useful way of generating fully active wild type SGK1. Ser377 and Ser422of SGK1, and the CDK7 T-loop peptide, which are phosphorylated by NEK6.	SIGNOR-250297
P17936	P68400	phosphorylation	up-regulates quantity by stabilization	0.338	The importance of Ser111 and Ser113 as targets for CK2 has also been shown in our laboratory, as mutation of either residue to alanine caused a major decrease in IGFBP-3 phosphorylation by this enzyme in vitro \| These results indicate that IGFBP-3 interaction with acid-labile subunit and with the cell surface, both of which involve basic carboxyl-terminal residues, may be modulated by phosphorylation. Relative resistance to proteolysis and poor binding to cells suggest that CK2-phospho-IGFBP-3 may be a significant inhibitor of IGF activity in the extracellular environment.	SIGNOR-250903
P15559	Q9Y4A8	transcriptional regulation	down-regulates quantity by repression	0.338	Deletion mutation analysis revealed that Nrf3 repression of NQO1 gene expression required heterodimerization and DNA binding domains but not transcriptional activation domain of Nrf3.	SIGNOR-268976
Q16513	Q15118	phosphorylation	up-regulates activity	0.338	PDK1 phosphorylates the PRKs at their conserved activation loop threonines (Thr-774 and Thr-816 for PRK1 and PRK2, respectively) both in vitro and in vivo.	SIGNOR-250265
O43566	P17612	phosphorylation	up-regulates activity	0.338	RGS14 is phosphorylated in vitro at Ser258 and Thr494 by PKA. cAMP-induced phosphorylation as an important modulator of RGS14 function since phosphorylation could enhance RGS14 binding to Galpha(i)-GDP	SIGNOR-250045
P12931	O14757	phosphorylation	up-regulates activity	0.338	In this study, we show that Chk1 phosphorylates human Src at the newly identified site serine 51 to fully induce Src kinase activity.	SIGNOR-278332
P67809	P78527	phosphorylation	up-regulates activity	0.338	The DNA-PK subunits and YB-1 phosphorylated at T89 were found colocalized suggesting their in vivo interaction.DNA-PK directly phosphorylates YB-1 and, this way, modulates YB-1 function. Point mutation of YB-1 at this residue abrogated the translocation of YB-1 into the nucleus.	SIGNOR-277611
P55087	P19784	phosphorylation	down-regulates activity	0.338	We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. \| To determine whether Ser276 is an actual CKII substrate, we used GST–AQP4‐Cter proteins in which only one out of the three C‐terminal CKII consensus sites was sequentially conserved (Ser276, Ser285 and Ser315, respectively). Figure 7B (right panel) shows that the three serine residues, including Ser276, were indeed efficiently phosphorylated by CKII.	SIGNOR-250976
Q9HB09	P49841	phosphorylation	up-regulates	0.338	Gsk3b phosphorylates bcl2l12 at s156. Ectopic expression of gfp-fused bcl2l12 or bcl2l12a in u87mg cells leads to repression of apoptotic markers and protects against staurosporine (sts) insults, indicating an antiapoptotic role for both bcl2l12 and bcl2l12a. In contrast, no anti-apoptotic ability was seen in bcl2l12(s156a)	SIGNOR-195512
Q712K3	P68400	phosphorylation	up-regulates activity	0.338	Ck2-dependent phosphorylation of the e2 ubiquitin conjugating enzyme ubc3b induces its interaction with beta-trcp and enhances beta-catenin degradation	SIGNOR-88050
P48426	P62330	null	up-regulates activity	0.338	Effects of ARF6 upon Axonogenesis Are Mediated by Phosphatidyl-inositol-4-phosphate 5-Kinase α. activated ARF6 stimulates the lipid-modifying enzyme PI(4)P 5-Kinase, leading to local increases in plasma membrane PIP2 and changes in actin dynamics. Alternatively, activation of Rac1 by upstream Rac1 activators or indirectly by ARF6-GTP results in stimulation of actin polymerization.	SIGNOR-264911
P05783	P06493	phosphorylation	up-regulates	0.338	We identified k18 ser33 as an interphase phosphorylation site, which increases its phosphorylation during mitosis in cultured cells and regenerating liver, and as an in vitro cdc2 kinase phosphorylation site. K18 ser33 phosphorylation dictates binding to 14_3_3 proteins	SIGNOR-55994
P30305	P68400	phosphorylation	up-regulates activity	0.338	Mass spectrometry analysis demonstrates that at least two serine residues, Ser-186 and Ser-187, are phosphorylated in vivo. \| Finally, we demonstrate that phosphorylation of CDC25B by protein kinase CK2 increases the catalytic activity of the phosphatase in vitro as well as in vivo.	SIGNOR-250836
O15525	P54821	binding	down-regulates activity	0.338	Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.	SIGNOR-221961
Q14790	Q9H4B4	phosphorylation	up-regulates activity	0.338	Furthermore, we identify caspase-8 as a new substrate for Plk3. Phosphorylation occurs on T273 and results in stimulation of caspase-8 proapoptotic function.	SIGNOR-272995
P67775	Q9Y314	ubiquitination	down-regulates quantity by destabilization	0.338	NOSIP mediates the monoubiquitination of the PP2A catalytic subunit and the loss of NOSIP results in an increase in PP2A activity in craniofacial tissue in NOSIP knockout mice.	SIGNOR-271498
P04637	Q8NEZ5	ubiquitination	down-regulates quantity by destabilization	0.338	We demonstrate here that SCFFbxo22-KDM4A is a senescence-associated E3 ligase targeting methylated p53 for degradation. We find that Fbxo22 is highly expressed in senescent cells in a p53-dependent manner, and that SCFFbxo22 ubiquitylated p53 and formed a complex with a lysine demethylase, KDM4A. \|SCFFbxo22 forms a ternary complex with p53 and KDM4A that targets methylated p53 for degradation.	SIGNOR-273448
O15266	P68400	phosphorylation	up-regulates	0.338	We show also that casein kinase ii phosphorylates shox on serine 106 efficiently in vitro. S106a shox mutant, defective in phosphorylation, does not activate transcription and fails to induce cell-cycle arrest and apoptosis	SIGNOR-142875
P17600	P17612	phosphorylation	down-regulates activity	0.338	Synapsin phosphorylation in the A domain, at the only phosphorylation site shared by all synapsins, dissociates synapsins from synaptic vesicles.This site is located in the N-terminal A domain and is a substrate for both PKA and CaM Kinase I	SIGNOR-250058
Q99623	Q16566	phosphorylation	down-regulates	0.338	Here we show that calcium/calmodulin-dependent kinase iv (camk iv) specifically binds to the c terminus of phb2 and phosphorylates phb2 at serine 91. Camk iv effectively decreased phb2-mediated repression of mef2 activity through phosphorylation	SIGNOR-174437
Q9BWT1	P31749	phosphorylation	down-regulates	0.338	The prosurvival kinase akt phosphorylates cdca7 at threonine 163, promoting binding to 14-3-3, dissociation from myc, and sequestration to the cytoplasm. we have mapped the domains of interaction and have discovered that akt phosphorylates cdca7 near this contact region, leading to loss of its association with myc, binding to 14-3-3 proteins, and exclusion from the nucleus.	SIGNOR-252533
P46937	O43318	phosphorylation	down-regulates activity	0.338	TAK1 inhibits YAP activity through beta-TRCP.\|Thus, our data indicate that TAK1 directly phosphorylates YAP at multiple sites.\|These observations prompted us to test whether TAK1 phosphorylates YAP at S127.	SIGNOR-278956
P09619	P23470	dephosphorylation	down-regulates activity	0.338	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-254715
P35125	P63000	relocalization	up-regulates	0.338	In quiescent cells, tre17 is localized to intracellular filamentous and punctate structures in the cytoplasm, folded in an inactive conformation. Upon growth factor addition, cdc42 and rac1 become activated and recruit tre17 to the plasma membrane. Stable membrane localization of tre17 also requires polymerized actin. This recruitment process leads to a conformational change in tre17, such that the n-terminal portion of the molecule further stimulates the accumulation of cortical actin.	SIGNOR-98938
Q06413	Q5JVS0	binding	down-regulates activity	0.338	MEF2C DNA-binding activity is inhibited through its interaction with the regulatory protein Ki-1/57.	SIGNOR-238283
P41240	P17612	phosphorylation	up-regulates activity	0.338	Activation of the cooh-terminal src kinase (csk) by camp-dependent protein kinase inhibits signaling through the t cell receptor.Pka phosphorylates csk at s364 in vitro and in vivo leading to a two- to fourfold increase in csk activity that is necessary for camp-mediated inhibition of tcr-induced interleukin 2 secretion.	SIGNOR-105229
P51790	Q9UQM7	phosphorylation	up-regulates activity	0.337	Identification of an N-terminal amino acid of the CLC-3 chloride channel critical in phosphorylation-dependent activation of a CaMKII-activated chloride current\|The N-terminus of CLC-3, which contains a CaMKII consensus sequence, was phosphorylated by CaMKII in vitro, and mutation of the serine at position 109 (S109A) abolished the CaMKII-dependent Cl(-) conductance, indicating that this residue is important in the gating of CLC-3 at the plasma membrane.	SIGNOR-275863
Q92542	O00141	phosphorylation	down-regulates quantity	0.337	Furthermore, SGK1 directly bound to and phosphorylated Nicastrin on Ser437, thereby promoting protein degradation.\|We showed that SGK1 downregulates Nicastrin protein levels.	SIGNOR-280122
Q9UK17	P12931	phosphorylation	up-regulates activity	0.337	These results indicate that Y108 (for Src-family kinases) and Y136 (for EGFR kinase) are involved in the tyrosine phosphorylation of hKv4.3 channels.	SIGNOR-276393
P15056	Q8NC42	polyubiquitination	down-regulates quantity by destabilization	0.337	We showed that RNF149 bound directly to the C-terminal kinase-containing domain of wild-type BRAF and induced ubiquitination, followed by proteasome-dependent degradation, of the latter protein. Functionally, RNF149 attenuated the increase in cell growth induced by wild-type BRAF.	SIGNOR-272043
Q13153	P35813	dephosphorylation	down-regulates activity	0.337	Purified PP2Cα protein efficiently dephosphorylated PAK1 in vitro (Fig. 1, D and E). We previously assessed the time course of phospho-PAK1 dephosphorylation assessed using specific antibodies against either Ser(P)198/203 or Thr(P)422 sites in the PAK1 activation loop.	SIGNOR-248492
P54132	O76064	ubiquitination	up-regulates activity	0.337	Here, we demonstrate that the ubiquitin/SUMO-dependent DNA damage response (UbS-DDR), controlled by the E3 ligases RNF8/RNF168, triggers BLM recruitment to sites of replication fork stalling via ubiquitylation in the N-terminal region of BLM and subsequent BLM binding to the ubiquitin-interacting motifs of .	SIGNOR-272115
Q92819	Q14541	transcriptional regulation	up-regulates quantity by expression	0.337	Transcription was activated by HNF4G in reporter assays using the promoter/enhancer region of the HAS2 gene. The endogenous expression of the HAS2 gene was suppressed by knockdown of HNF4G.	SIGNOR-261626
P05455	P68400	phosphorylation	up-regulates	0.337	Prior studies indicate that hla is activated by phosphorylation of serine-366 by protein kinase ck2, neutralizing a negative effect of a short basic motif (sbm)	SIGNOR-160761
P49768	Q05513	phosphorylation	up-regulates activity	0.337	A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis.	SIGNOR-249239
O75509	P01375	binding	up-regulates	0.337	We report the identification and initial characterization of dr6, a new member of the tnf receptor family possessing a cytoplasmic death domain.	SIGNOR-59745
O15164	O43791	binding	down-regulates quantity by destabilization	0.337	Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations.	SIGNOR-272825
O75581	Q03431	binding	up-regulates	0.337	Parathyroid hormone (pth) binding to its receptor pth1r induces association of the pthpth1r complex with lrp6and phosphorylation of pppsp sites by protein kinase_ a, which in turn triggers wnt.	SIGNOR-199533
Q92186	Q7Z6R9	transcriptional regulation	up-regulates quantity by expression	0.337	We use chromatin immunoprecipitation and gel shift assays to demonstrate direct interaction between AP-2 and the ST8SIA2 promoter.\|We show that ST8SIA2 is induced by AP-2δ overexpression in chick retina. We use chromatin immunoprecipitation and gel shift assays to demonstrate direct interaction between AP-2δ and the ST8SIA2 promoter.	SIGNOR-268992
Q15796	Q92830	binding	up-regulates	0.337	Gcn5 functions like pcaf, in that it binds to tgf-beta-specific r-smads, and enhances transcriptional activity induced by tgf-beta. In addition, gcn5, but not pcaf, interacts with r-smads for bone morphogenetic protein (bmp) signalling pathways, and enhances bmp-induced transcriptional activity, suggesting that gcn5 and pcaf have distinct physiological functions in vivo.	SIGNOR-123315
Q96MM3	Q9NVW2	ubiquitination	down-regulates quantity by destabilization	0.337	RNF12 causes ubiquitination and proteasomal degradation of REX1, and Rnf12 knockout embryonic stem cells show an increased level of REX1.	SIGNOR-269002
Q2M1Z3	P49840	phosphorylation	up-regulates activity	0.337	We show that GSK-3alpha and -beta interact with CdGAP in mammalian cells. We also demonstrate that GSK-3 phosphorylates CdGAP both in vitro and in vivo on Thr-776, which we have previously shown to be an ERK 1/2 phosphorylation site involved in CdGAP regulation.	SIGNOR-262878
P04637	Q9H0A0	acetylation	up-regulates quantity by stabilization	0.337	NAT10 acetylates p53 at K120 and stabilizes p53 by counteracting Mdm2 action. In addition, NAT10 promotes Mdm2 degradation with its intrinsic E3 ligase activity.	SIGNOR-272406
P07101	O75582	phosphorylation	up-regulates	0.337	Recombinant human tyrosine hydroxylase (hth1) was found to be phosphorylated by mitogen and stress-activated protein kinase 1 (msk1) at ser40 and by p38 regulated/activated kinase (prak) on ser19. Phosphorylation by msk1 induced an increase in vmax. studies on th from several species suggest that ser40 is the main site involved in direct activation of th	SIGNOR-95491
Q9BUR4	Q13315	phosphorylation	up-regulates activity	0.337	Here, we show that in response to various types of DNA damage, including IR and UV, WRAP53β is phosphorylated on serine residue 64 by ATM with a time-course that parallels its accumulation at DNA lesions. Interestingly, recruitment of phosphorylated WRAP53β (pWRAP53βS64) to sites of such DNA damage promotes its interaction with γH2AX at these locations.	SIGNOR-273511
P01106	Q01196	transcriptional regulation	down-regulates quantity by repression	0.337	RUNX1 represses MYC expression through direct binding at three downstream enhancer elements	SIGNOR-260093
P01236	Q13177	phosphorylation	up-regulates	0.337	Phosphorylated form of prolactin has a higher affinity for heparin.	SIGNOR-186211
P04818	P01106	transcriptional regulation	up-regulates quantity by expression	0.337	Analysis of in vivo C-MYC interactions with TS, IMPDH2 and PRPS2 genes confirmed that they are direct C-MYC targets. C-MYC depletion did not significantly affect levels of E2F1 protein reported to regulate expression of many S-phase specific genes, but resulted in the repression of several genes encoding enzymes rate-limiting for dNTP metabolism. These included thymidylate synthase (TS), inosine monophosphate dehydrogenase 2 (IMPDH2) and phosphoribosyl pyrophosphate synthetase 2 (PRPS2). C-MYC depletion also resulted in reduction in the amounts of deoxyribonucleoside triphosphates (dNTPs) and inhibition of proliferation.	SIGNOR-267374
P20226	Q7Z6Z7	ubiquitination	down-regulates quantity	0.337	Having established that Huwe1 mediates TBP ubiquitination in vitro, we then asked which E2 conjugating enzymes work best with Huwe1 in this reaction.\|Upregulation of Huwe1 expression during myogenesis induces TBP degradation and myotube differentiation.	SIGNOR-278696
Q8N752	A6ND36	binding	up-regulates quantity	0.337	We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.	SIGNOR-273753
P30086	Q00535	phosphorylation	down-regulates quantity by destabilization	0.337	Here, we demonstrate that RKIP is a substrate of cyclin-dependent kinase 5 (CDK5) in neurons and that the phosphorylation of RKIP at T42 causes the release of Raf-1. Moreover, T42 phosphorylation promotes the exposure and recognition of the target motif "KLYEQ" in the C-terminus of RKIP by chaperone Hsc70 and the subsequent degradation of RKIP via chaperone-mediated autophagy (CMA).	SIGNOR-276672
P12755	P31749	phosphorylation	down-regulates	0.337	The phosphorylation of ski at threonine 458 is induced by akt pathway activators including insulin, insulin-like growth factor-1, and hepatocyte growth factor. The phosphorylation of ski causes its destabilization and reduces ski-mediated inhibition of expression of another negative regulator of tgf-beta, smad7	SIGNOR-252527
P48775	P04150	transcriptional regulation	down-regulates quantity by repression	0.337	Repression of GR-mediated expression of the tryptophan oxygenase gene by the SWI/SNF complex during liver development.	SIGNOR-268995
P84022	P78368	phosphorylation	down-regulates	0.337	Cki?2 Directly phosphorylates smad3 at ser418, leading to the increased ubiquitination and proteasomal degradation of activated smad3 following tgf-? Treatment.	SIGNOR-181069
Q15078	P15882	binding	up-regulates	0.337	_-chimaerin was identified to interact with the p35 activator of cdk5. The complex of _-chimaerin, cdk5 and p35 is enzymatically functional	SIGNOR-123439
Q9UNH5	Q7Z569	polyubiquitination	up-regulates activity	0.337	Brap2 promotes Lys-63 linked ubiquitination of HsCdc14A. Collectively, these results support the idea that Brap2 facilitates Lys-63 linked ubiquitin modification of HsCdc14A, which may not be targeted for degradation, but mainly for protein–protein interactions or other regulatory functions.	SIGNOR-271777
Q13153	P27361	phosphorylation	down-regulates	0.337	Activated erk can phosphorylate t292 in the prs, and this blocks the ability of pak to phosphorylate s298 and of rac-pak signaling to enhance mek1-erk complex formation.	SIGNOR-123074
P15509	P09603	binding	up-regulates	0.337	Granulocyte-macrophage colony-stimulating factor (gm-csf) is an important hematopoietic cytokine that exerts its effects by interaction with the gm-csf receptor (gmr) on the surface of responsive cells. The gm-csf receptor consists of two subunits: gmralpha, which binds gm-csf with low affinity, and gmrbeta, which lacks intrinsic ligand-binding capability but complexes with gmralpha to form a high-affinity receptor (gmralpha/beta).	SIGNOR-72455
Q16584	P49841	phosphorylation	up-regulates activity	0.336	Further, investigation revealed that MLK3 was phosphorylated at two residues Ser789 and Ser793 by GSK3\u03b2 ( xref ).\|When, these two sites on MLK3 were mutated to non-phosphorable Ala, the activation of MLK3 by GSK3\u03b2 was blocked, and neuronal cell death upon NGF withdrawal also prevented ( xref ).	SIGNOR-279615
Q99640	P45983	phosphorylation	up-regulates	0.336	A kinase assay using gst-myt1 revealed that active jnk1 or jnk3, but not jnk2, phosphorylated myt1 in vitro.	SIGNOR-183899
P78357	P12931	phosphorylation	down-regulates activity	0.336	If that is the case, then our genetic results support the notion that p190 is negatively regulated by both Src and integrin.\|The Src family of tyrosine kinases phosphorylate mammalian p190.	SIGNOR-279572
Q9UQ80	P35637	sumoylation	up-regulates activity	0.336	Here, we show that Ebp1 p42 isoform can be sumoylated on both K93 and K298 residues, which mediate its nuclear translocation and are required for its anti-proliferative activity .. Hence, TLS-mediated sumoylation is required for Ebp1 transcriptional repressive activity.	SIGNOR-236904
P01584	Q16665	transcriptional regulation	up-regulates quantity by expression	0.336	We finally confirmed that in the absence of HIF-1α there was a significant reduction at the protein level in pro-caspase-1, activated caspase-1, pro-IL-1β, and ultimately active IL-1β (Fig. 4g and h). These data show that adenosine induced up-regulation of IL-1β is dependent on a CREB/HIF-1α pathway which is distinct from the NF-kB pathway used for initial production of IL-1β in response to LPS.	SIGNOR-251718
Q9BT92	Q8N5Z5	binding	down-regulates quantity by destabilization	0.336	We have identified KCTD17 as a substrate-adaptor for Cul3-RING E3 ligases (CRL3s) that polyubiquitylates trichoplein. Depletion of KCTD17 specifically arrests ciliogenesis at the initial step of axoneme extension through aberrant trichoplein-Aurora-A activity. Thus, CRL3-KCTD17 targets trichoplein to proteolysis to initiate the axoneme extension during ciliogenesis.	SIGNOR-272463
P00533	P10586	dephosphorylation	down-regulates activity	0.336	Some 10 years ago, Hashimoto et al. (87) had shown that the LAR catalytic domain can dephosphorylate the EGFR receptor in vitro, and more recently, Kulas and colleagues (88) have demonstrated that the antisense mediated suppression of LAR can enhance the growth factor induced activation of EGFR in rat hepatoma cells.\|These data indicate that LAR and RPTPsigma may have a significant role in GPCR induced EGFR signalling.Whereas in A431 cells LAR and RPTPsigma may act to suppress the EGFR in response to GPCR activation, it is possible that the converse may also be true in other cell types.	SIGNOR-277029
O15350	O15111	phosphorylation	up-regulates activity	0.336	IKK-alpha had an ability to stabilize p73 by inhibiting its polyubiquitination, and enhanced p73 mediated transcriptional activation as well as proapoptotic activity.\|In addition, IKK-alpha phosphorylated the NH 2 -terminal portion of p73 and a kinase deficient mutant form of IKK-alpha had undetectable effect on p73.	SIGNOR-279697
Q01094	Q13490	ubiquitination	up-regulates activity	0.336	The ability of cIAP1 to promote wt E2F1 transcriptional activity was retained by all E2F1 mutants, except the K161R/164R mutant for which cIAP1 was completely inactive and the K185R whose basal transactivation activity was weakly enhanced by cIAP1 (XREF_FIG).\|Here, we demonstrated that the E3-ubiquitin ligase cellular inhibitor of apoptosis 1 (cIAP1) increases E2F1 K63-poly-ubiquitination on the lysine residue 161/164 cluster, which is associated with the transcriptional factor stability and activity.	SIGNOR-278688
Q14790	Q5T447	polyubiquitination	down-regulates activity	0.336	HECTD3, a new E3 ubiquitin ligase, interacts with caspase-8 death effector domains and ubiquitinates caspase-8 with K63-linked polyubiquitin chains that do not target caspase-8 for degradation but decrease the caspase-8 activation. HECTD3 ubiquitinates caspase-8 with K63-linked polyubiquitin chains at K215.	SIGNOR-272077
P04637	P51812	phosphorylation	up-regulates activity	0.336	Here we show that ribosomal S6 kinase 2 (RSK2) activates and phosphorylates p53 (Ser15) in vitro and in vivo and colocalizes with p53 in the nucleus.	SIGNOR-279567
Q04721	Q4G148	binding	up-regulates	0.336	We have previously identified two human genes, gxylt1 and gxylt2, encoding glucoside xylosyltransferases responsible for the transfer of xylose to o-linked glucose. The identity of the enzyme further elongating the glycan to generate the final trisaccharide xylose-xylose-glucose, however, remained unknown. Here, we describe that the human gene c3orf21 encodes a udp-xylose:alfa-xyloside alfa1,3-xylosyltransferase, acting on xylose-alfa1,3-glucosebeta1-containing acceptor structures. We have, therefore, renamed it xxylt1 (xyloside xylosyltransferase 1). Xxylt1 cannot act on a synthetic acceptor containing an alfa-linked xylose alone, but requires the presence of the underlying glucose. Activity on notch egf repeats was proven by in vitro xylosylation of a mouse notch1 fragment recombinantly produced in sf9 insect cells, a bacterially expressed egf repeat from mouse notch2 modified in vitro by rumi and gxylt2 and in vivo by co-expression of the enzyme with the notch1 fragment. The enzyme was shown to be a typical type ii membrane-bound glycosyltransferase localized in the endoplasmic reticulum.	SIGNOR-177694
P11473	P68400	phosphorylation	up-regulates	0.336	Casein kinase ii (ckii) phosphorylates vdr both in vitro and in vivo at serine 208 within the hinge domain. This phosphorylation does not affect the ability of vdr to bind dna, but increases its ability to transactivate target promoters	SIGNOR-153711
P01112	Q8TEU7	guanine nucleotide exchange factor	up-regulates	0.336	Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.	SIGNOR-183796
P50148	P07550	binding	up-regulates activity	0.336	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257081
Q8IXH7	P12931	phosphorylation	down-regulates activity	0.336	Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of TH1 at Tyr-6 in vivo and in vitro. Phosphorylation of TH1 decreases its association with A-Raf and PAK1.	SIGNOR-276402
Q9UM54	O75914	phosphorylation	up-regulates activity	0.336	P21-activated kinase 3 phosphorylated myosin VI, and the site was identified as Thr(406). The phosphorylation of myosin VI significantly facilitated the actin-translocating activity of myosin VI.	SIGNOR-250244
P15941	Q05655	phosphorylation	up-regulates	0.336	We show that phosphorylation of muc1 by pkcdelta increases binding of muc1 and beta-catenin in vitro and in vivo. The functional significance of the muc1-pkcdelta interaction is further supported by the demonstration that mutation of the pkcdelta phosphorylation site abrogates muc1-mediated decreases in binding of beta-catenin to e-cadherin	SIGNOR-115501
O43504	Q13315	phosphorylation	up-regulates activity	0.336	Strikingly, we found that the kinase ataxia telangiectasia mutated (ATM) phosphorylated HBXIP at Ser (108).\|The knockdown of ATM by siRNA remarkably decreased the levels of serine phosphorylation and blocked the nuclear import of HBXIP.	SIGNOR-279791
Q01105	P48736	phosphorylation	up-regulates activity	0.336	We show that PI3Kgamma phosphorylates I2PP2A on serine 9 and 93 residues resulting in enhanced interaction of I2PP2A with PP2A.	SIGNOR-278320
Q9UM11	Q86T82	binding	down-regulates activity	0.336	Here we show that USP37 binds the APC/C coactivator CDH1\|Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry	SIGNOR-265054
P06400	Q00535	phosphorylation	down-regulates	0.336	Phosphorylation was observed 6 hours after p25 induction and was abolished in the presence of a cdk5 inhibitor, roscovitine, which does not inhibit the usual rb cyclin-d kinases cdk4 and cdk6. Furthermore, analyses of levels and subcellular localization of cdk-related cyclins did not reveal any change following cdk5 activation, arguing for a direct effect of cdk5 activity on rb protein. Rb phosphorylation was visualized using phosphorylation-dependent antibodies (p-rbser795 and p-rbser807/811).	SIGNOR-134468

Q92858

O60674

0

phosphorylation

up-regulates quantity

0.339

We discovered tyrosine 78 of Atoh1 is phosphorylated by a Jak2-mediated pathway only in tumor-initiating cells and in human SHH-type medulloblastoma. Phosphorylation of tyrosine 78 stabilizes Atoh1, increases Atoh1’s transcriptional activity, and is independent of canonical Jak2 signaling.

SIGNOR-262201

P06127

P17252

0

phosphorylation

up-regulates

0.339

Cd5 is a good pkc substrate. Phosphorylation of cd5 is necessary for cd5-mediated lipid second messenger generation.

SIGNOR-85179

P29590

P27361

0

phosphorylation

up-regulates

0.339

Phosphorylation of pml by mitogen-activated protein kinases plays a key role in arsenic trioxide-mediated apoptosis.

SIGNOR-124317

P10915

P08253

0

cleavage

down-regulates quantity by destabilization

0.339

Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix.

SIGNOR-256333

P61978

P53779

0

phosphorylation

up-regulates activity

0.339

JNK Phosphorylation of HnRNP K Increases Its Transcriptional Activity. the primary site for JNK phosphorylation consists of serines 216 and 353 on the K protein.

SIGNOR-250083

P78344

P06493

0

phosphorylation

up-regulates activity

0.339

To test whether CDK1 phosphorylates T508, Flag-DAP5 was purified from dox-induced HEK293 cells and incubated with active recombinant JNK2 or CDK1 in the presence of ATP (Fig. 3G). DAP5(T508) was phosphorylated only upon incubation with CDK1 (Fig. 3G).

SIGNOR-266387

Q9BXM7

O75439

0

cleavage

down-regulates quantity by destabilization

0.339

Using an unbiased RNA-mediated interference (RNAi)-based screen, we identified four mitochondrial proteases, mitochondrial processing peptidase (MPP), presenilin-associated rhomboid-like protease (PARL), m-AAA and ClpXP, involved in PINK1 degradation. We find that PINK1 turnover is particularly sensitive to even modest reductions in MPP levels. Moreover, PINK1 cleavage by MPP is coupled to import such that reducing MPP activity induces PINK1 accumulation at the mitochondrial surface, leading to Parkin recruitment and mitophagy.

SIGNOR-261363

Q9NX09

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.339

It has been reported that GSK3beta phosphorylates REDD1 at residues Thr23 and Thr25, resulting in REDD1 recruitment to the Cullin 4a-beta-Trcp E3 ligase complex.

SIGNOR-279526

Q9UPP1

Q12834

0

binding

down-regulates quantity by destabilization

0.339

We showed that PHF8 interacts with the CDC20-containing APC (APC(cdc20)) primarily during mitosis. we demonstrate that mutations of the LXPKXLF motif abrogate polyubiquitylation of PHF8 by the APC. APC substrates are typically cell cycle regulators, and consistent with this, the loss of PHF8 leads to prolonged G2 phase and defective mitosis.

SIGNOR-272879

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

P27707

P48730

0

phosphorylation

up-regulates activity

0.339

Site-directed mutagenesis demonstrated that only Ser-74 phosphorylation was involved in Deoxycytidine kinase activation by CKI delta, strengthening the key role of this residue in the control of Deoxycytidine kinase activity.|We showed that recombinant CKI delta phosphorylated several residues of bacterially overexpressed Deoxycytidine kinase: Ser-74, but also Ser-11, Ser-15, and Thr-72.

SIGNOR-280233

O75164

Q8NEZ5

0

ubiquitination

down-regulates quantity by destabilization

0.339

SCF(FBXO22) regulates histone H3 lysine 9 and 36 methylation levels by targeting histone demethylase KDM4A for ubiquitin-mediated proteasomal degradation

SIGNOR-273442

P56945

P10586

0

dephosphorylation

down-regulates quantity by destabilization

0.339

LAR specifically dephosphorylates and destabilizes p130Cas and may play a role in regulating cell adhesion-mediated cell survival.|Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130Cas.

SIGNOR-276998

P25440

Q96DB2

0

binding

down-regulates activity

0.339

Ex vivo and cell-based assays revealed that HDAC11 catalytic activity suppresses the BAT transcriptional program, in both the basal state and in response to β-adrenergic receptor signaling, through a mechanism that is dependent on physical association with BRD2, a bromodomain and extraterminal (BET) acetyl-histone-binding protein.

SIGNOR-262058

P35568

P19525

0

phosphorylation

down-regulates activity

0.339

First, PKR induces phosphorylation of IRS1 at Ser312 and suppresses tyrosine phosphorylation of IRS1, mediated by the insulin receptor substrates kinases, JNK and I\u03baB kinase.|These results suggest that PKR induces the inhibitory phosphorylation of IRS1 at Ser312 in HepG2 cells, thereby suppressing the phosphorylation at Tyr941.

SIGNOR-278310

O43603

Q9BT56

0

binding

up-regulates activity

0.339

Coevolution of the spexin/galanin/kisspeptin family: Spexin activates galanin receptor type II and III.

SIGNOR-268574

Q14315

P17252

0

phosphorylation

up-regulates quantity by stabilization

0.338

We identified the extended basophilic phosphosite motif RxRxxp[S/T]xxp[S/T] in various proteins including filamin-C (FLNc). Importantly, this extended motif, located in a unique insert in Ig-like domain 20 of FLNc, is doubly phosphorylated. The protein kinases responsible for this dual-site phosphorylation are Akt and PKCα. Proximity proteomics and interaction analysis identified filamin A-interacting protein 1 (FILIP1) as direct FLNc binding partner. FILIP1 binding induces filamin degradation, thereby negatively regulating its function. Here, dual-site phosphorylation of FLNc not only reduces FILIP1 binding, providing a mechanism to shield FLNc from FILIP1-mediated degradation, but also enables fast dynamics of FLNc necessary for its function as signaling adaptor in cross-striated muscle cells. In vitro kinase assays combined with LC-MS confirmed hFLNc-S2233 as a substrate of Akt, whereas PKCα preferentially targeted S2236.

SIGNOR-262617

Q8NEG5

P51965

0

binding

up-regulates activity

0.338

MEX can act as an E3, Ub (ubiquitin) ligase, through the E2, Ub-conjugating enzymes UbcH5a, UbcH5c or UbcH6. A region of MEX that contains the RING fingers and the ZZ zinc finger was required for interaction with UbcH5a and MEX self-association, whereas the SWIM domain was critical for MEX ubiquitination. The expression of MEX promoted apoptosis that was induced through Fas, DR (death receptor) 3 and DR4 signalling, but not that mediated by the BH3 (Bcl-2 homology 3)-only protein BimEL or the chemotherapeutic drug adriamycin.

SIGNOR-271555

P31947

P45983

0

phosphorylation

down-regulates

0.338

Jnk phosphorylates 14-3-3zeta_ at ser-184 and 14-3-3sigma_ at ser-187.

SIGNOR-124016

O95786

Q13283

0

binding

down-regulates activity

0.338

G3BP1 binds RIG-I and that this interaction involves the C-terminal RGG domain of G3BP1, G3BP1 significantly enhances RIG-I-induced ifn-b mRNA synthesis.

SIGNOR-260980

O00141

Q9HC98

0

phosphorylation

up-regulates activity

0.338

The present study is the first report of a protein kinase (NEK6) capable of phosphorylating the hydrophobic motif of SGK1, although our data suggest that NEK6 may not mediate this reaction in cells. Nevertheless, the phosphorylation of the hydrophobic motif of SGK1in vitro, coupled with the phosphorylation of the T-loop with PDK1, may be a useful way of generating fully active wild type SGK1. Ser377 and Ser422of SGK1, and the CDK7 T-loop peptide, which are phosphorylated by NEK6.

SIGNOR-250297

P17936

P68400

0

phosphorylation

up-regulates quantity by stabilization

0.338

The importance of Ser111 and Ser113 as targets for CK2 has also been shown in our laboratory, as mutation of either residue to alanine caused a major decrease in IGFBP-3 phosphorylation by this enzyme in vitro | These results indicate that IGFBP-3 interaction with acid-labile subunit and with the cell surface, both of which involve basic carboxyl-terminal residues, may be modulated by phosphorylation. Relative resistance to proteolysis and poor binding to cells suggest that CK2-phospho-IGFBP-3 may be a significant inhibitor of IGF activity in the extracellular environment.

SIGNOR-250903

P15559

Q9Y4A8

0

transcriptional regulation

down-regulates quantity by repression

0.338

Deletion mutation analysis revealed that Nrf3 repression of NQO1 gene expression required heterodimerization and DNA binding domains but not transcriptional activation domain of Nrf3.

SIGNOR-268976

Q16513

Q15118

0

phosphorylation

up-regulates activity

0.338

PDK1 phosphorylates the PRKs at their conserved activation loop threonines (Thr-774 and Thr-816 for PRK1 and PRK2, respectively) both in vitro and in vivo.

SIGNOR-250265

O43566

P17612

0

phosphorylation

up-regulates activity

0.338

RGS14 is phosphorylated in vitro at Ser258 and Thr494 by PKA. cAMP-induced phosphorylation as an important modulator of RGS14 function since phosphorylation could enhance RGS14 binding to Galpha(i)-GDP

SIGNOR-250045

P12931

O14757

0

phosphorylation

up-regulates activity

0.338

In this study, we show that Chk1 phosphorylates human Src at the newly identified site serine 51 to fully induce Src kinase activity.

SIGNOR-278332

P67809

P78527

0

phosphorylation

up-regulates activity

0.338

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

SIGNOR-277611

P55087

P19784

0

phosphorylation

down-regulates activity

0.338

We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. | To determine whether Ser276 is an actual CKII substrate, we used GST–AQP4‐Cter proteins in which only one out of the three C‐terminal CKII consensus sites was sequentially conserved (Ser276, Ser285 and Ser315, respectively). Figure 7B (right panel) shows that the three serine residues, including Ser276, were indeed efficiently phosphorylated by CKII.

SIGNOR-250976

Q9HB09

P49841

0

phosphorylation

up-regulates

0.338

Gsk3b phosphorylates bcl2l12 at s156. Ectopic expression of gfp-fused bcl2l12 or bcl2l12a in u87mg cells leads to repression of apoptotic markers and protects against staurosporine (sts) insults, indicating an antiapoptotic role for both bcl2l12 and bcl2l12a. In contrast, no anti-apoptotic ability was seen in bcl2l12(s156a)

SIGNOR-195512

Q712K3

P68400

0

phosphorylation

up-regulates activity

0.338

Ck2-dependent phosphorylation of the e2 ubiquitin conjugating enzyme ubc3b induces its interaction with beta-trcp and enhances beta-catenin degradation

SIGNOR-88050

P48426

P62330

0

null

up-regulates activity

0.338

Effects of ARF6 upon Axonogenesis Are Mediated by Phosphatidyl-inositol-4-phosphate 5-Kinase α. activated ARF6 stimulates the lipid-modifying enzyme PI(4)P 5-Kinase, leading to local increases in plasma membrane PIP2 and changes in actin dynamics. Alternatively, activation of Rac1 by upstream Rac1 activators or indirectly by ARF6-GTP results in stimulation of actin polymerization.

SIGNOR-264911

P05783

P06493

0

phosphorylation

up-regulates

0.338

We identified k18 ser33 as an interphase phosphorylation site, which increases its phosphorylation during mitosis in cultured cells and regenerating liver, and as an in vitro cdc2 kinase phosphorylation site. K18 ser33 phosphorylation dictates binding to 14_3_3 proteins

SIGNOR-55994

P30305

P68400

0

phosphorylation

up-regulates activity

0.338

Mass spectrometry analysis demonstrates that at least two serine residues, Ser-186 and Ser-187, are phosphorylated in vivo. | Finally, we demonstrate that phosphorylation of CDC25B by protein kinase CK2 increases the catalytic activity of the phosphatase in vitro as well as in vivo.

SIGNOR-250836

O15525

P54821

0

binding

down-regulates activity

0.338

Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.

SIGNOR-221961

Q14790

Q9H4B4

0

phosphorylation

up-regulates activity

0.338

Furthermore, we identify caspase-8 as a new substrate for Plk3. Phosphorylation occurs on T273 and results in stimulation of caspase-8 proapoptotic function.

SIGNOR-272995

P67775

Q9Y314

0

ubiquitination

down-regulates quantity by destabilization

0.338

NOSIP mediates the monoubiquitination of the PP2A catalytic subunit and the loss of NOSIP results in an increase in PP2A activity in craniofacial tissue in NOSIP knockout mice.

SIGNOR-271498

P04637

Q8NEZ5

0

ubiquitination

down-regulates quantity by destabilization

0.338

We demonstrate here that SCFFbxo22-KDM4A is a senescence-associated E3 ligase targeting methylated p53 for degradation. We find that Fbxo22 is highly expressed in senescent cells in a p53-dependent manner, and that SCFFbxo22 ubiquitylated p53 and formed a complex with a lysine demethylase, KDM4A. |SCFFbxo22 forms a ternary complex with p53 and KDM4A that targets methylated p53 for degradation.

SIGNOR-273448

O15266

P68400

0

phosphorylation

up-regulates

0.338

We show also that casein kinase ii phosphorylates shox on serine 106 efficiently in vitro. S106a shox mutant, defective in phosphorylation, does not activate transcription and fails to induce cell-cycle arrest and apoptosis

SIGNOR-142875

P17600

P17612

0

phosphorylation

down-regulates activity

0.338

Synapsin phosphorylation in the A domain, at the only phosphorylation site shared by all synapsins, dissociates synapsins from synaptic vesicles.This site is located in the N-terminal A domain and is a substrate for both PKA and CaM Kinase I

SIGNOR-250058

Q99623

Q16566

0

phosphorylation

down-regulates

0.338

Here we show that calcium/calmodulin-dependent kinase iv (camk iv) specifically binds to the c terminus of phb2 and phosphorylates phb2 at serine 91. Camk iv effectively decreased phb2-mediated repression of mef2 activity through phosphorylation

SIGNOR-174437

Q9BWT1

P31749

0

phosphorylation

down-regulates

0.338

The prosurvival kinase akt phosphorylates cdca7 at threonine 163, promoting binding to 14-3-3, dissociation from myc, and sequestration to the cytoplasm. we have mapped the domains of interaction and have discovered that akt phosphorylates cdca7 near this contact region, leading to loss of its association with myc, binding to 14-3-3 proteins, and exclusion from the nucleus.

SIGNOR-252533

P46937

O43318

0

phosphorylation

down-regulates activity

0.338

TAK1 inhibits YAP activity through beta-TRCP.|Thus, our data indicate that TAK1 directly phosphorylates YAP at multiple sites.|These observations prompted us to test whether TAK1 phosphorylates YAP at S127.

SIGNOR-278956

P09619

P23470

0

dephosphorylation

down-regulates activity

0.338

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-254715

P35125

P63000

0

relocalization

up-regulates

0.338

In quiescent cells, tre17 is localized to intracellular filamentous and punctate structures in the cytoplasm, folded in an inactive conformation. Upon growth factor addition, cdc42 and rac1 become activated and recruit tre17 to the plasma membrane. Stable membrane localization of tre17 also requires polymerized actin. This recruitment process leads to a conformational change in tre17, such that the n-terminal portion of the molecule further stimulates the accumulation of cortical actin.

SIGNOR-98938

Q06413

Q5JVS0

0

binding

down-regulates activity

0.338

MEF2C DNA-binding activity is inhibited through its interaction with the regulatory protein Ki-1/57.

SIGNOR-238283

P41240

P17612

0

phosphorylation

up-regulates activity

0.338

Activation of the cooh-terminal src kinase (csk) by camp-dependent protein kinase inhibits signaling through the t cell receptor.Pka phosphorylates csk at s364 in vitro and in vivo leading to a two- to fourfold increase in csk activity that is necessary for camp-mediated inhibition of tcr-induced interleukin 2 secretion.

SIGNOR-105229

P51790

Q9UQM7

0

phosphorylation

up-regulates activity

0.337

Identification of an N-terminal amino acid of the CLC-3 chloride channel critical in phosphorylation-dependent activation of a CaMKII-activated chloride current|The N-terminus of CLC-3, which contains a CaMKII consensus sequence, was phosphorylated by CaMKII in vitro, and mutation of the serine at position 109 (S109A) abolished the CaMKII-dependent Cl(-) conductance, indicating that this residue is important in the gating of CLC-3 at the plasma membrane.

SIGNOR-275863

Q92542

O00141

0

phosphorylation

down-regulates quantity

0.337

Furthermore, SGK1 directly bound to and phosphorylated Nicastrin on Ser437, thereby promoting protein degradation.|We showed that SGK1 downregulates Nicastrin protein levels.

SIGNOR-280122

Q9UK17

P12931

0

phosphorylation

up-regulates activity

0.337

These results indicate that Y108 (for Src-family kinases) and Y136 (for EGFR kinase) are involved in the tyrosine phosphorylation of hKv4.3 channels.

SIGNOR-276393

P15056

Q8NC42

0

polyubiquitination

down-regulates quantity by destabilization

0.337

We showed that RNF149 bound directly to the C-terminal kinase-containing domain of wild-type BRAF and induced ubiquitination, followed by proteasome-dependent degradation, of the latter protein. Functionally, RNF149 attenuated the increase in cell growth induced by wild-type BRAF.

SIGNOR-272043

Q13153

P35813

0

dephosphorylation

down-regulates activity

0.337

Purified PP2Cα protein efficiently dephosphorylated PAK1 in vitro (Fig. 1, D and E). We previously assessed the time course of phospho-PAK1 dephosphorylation assessed using specific antibodies against either Ser(P)198/203 or Thr(P)422 sites in the PAK1 activation loop.

SIGNOR-248492

P54132

O76064

0

ubiquitination

up-regulates activity

0.337

Here, we demonstrate that the ubiquitin/SUMO-dependent DNA damage response (UbS-DDR), controlled by the E3 ligases RNF8/RNF168, triggers BLM recruitment to sites of replication fork stalling via ubiquitylation in the N-terminal region of BLM and subsequent BLM binding to the ubiquitin-interacting motifs of .

SIGNOR-272115

Q92819

Q14541

0

transcriptional regulation

up-regulates quantity by expression

0.337

Transcription was activated by HNF4G in reporter assays using the promoter/enhancer region of the HAS2 gene. The endogenous expression of the HAS2 gene was suppressed by knockdown of HNF4G.

SIGNOR-261626

P05455

P68400

0

phosphorylation

up-regulates

0.337

Prior studies indicate that hla is activated by phosphorylation of serine-366 by protein kinase ck2, neutralizing a negative effect of a short basic motif (sbm)

SIGNOR-160761

P49768

Q05513

0

phosphorylation

up-regulates activity

0.337

A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis.

SIGNOR-249239

O75509

P01375

0

binding

up-regulates

0.337

We report the identification and initial characterization of dr6, a new member of the tnf receptor family possessing a cytoplasmic death domain.

SIGNOR-59745

O15164

O43791

0

binding

down-regulates quantity by destabilization

0.337

Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations.

SIGNOR-272825

O75581

Q03431

0

binding

up-regulates

0.337

Parathyroid hormone (pth) binding to its receptor pth1r induces association of the pthpth1r complex with lrp6and phosphorylation of pppsp sites by protein kinase_ a, which in turn triggers wnt.

SIGNOR-199533

Q92186

Q7Z6R9

0

transcriptional regulation

up-regulates quantity by expression

0.337

We use chromatin immunoprecipitation and gel shift assays to demonstrate direct interaction between AP-2 and the ST8SIA2 promoter.|We show that ST8SIA2 is induced by AP-2δ overexpression in chick retina. We use chromatin immunoprecipitation and gel shift assays to demonstrate direct interaction between AP-2δ and the ST8SIA2 promoter.

SIGNOR-268992

Q15796

Q92830

0

binding

up-regulates

0.337

Gcn5 functions like pcaf, in that it binds to tgf-beta-specific r-smads, and enhances transcriptional activity induced by tgf-beta. In addition, gcn5, but not pcaf, interacts with r-smads for bone morphogenetic protein (bmp) signalling pathways, and enhances bmp-induced transcriptional activity, suggesting that gcn5 and pcaf have distinct physiological functions in vivo.

SIGNOR-123315

Q96MM3

Q9NVW2

0

ubiquitination

down-regulates quantity by destabilization

0.337

RNF12 causes ubiquitination and proteasomal degradation of REX1, and Rnf12 knockout embryonic stem cells show an increased level of REX1.

SIGNOR-269002

Q2M1Z3

P49840

0

phosphorylation

up-regulates activity

0.337

We show that GSK-3alpha and -beta interact with CdGAP in mammalian cells. We also demonstrate that GSK-3 phosphorylates CdGAP both in vitro and in vivo on Thr-776, which we have previously shown to be an ERK 1/2 phosphorylation site involved in CdGAP regulation.

SIGNOR-262878

P04637

Q9H0A0

0

acetylation

up-regulates quantity by stabilization

0.337

NAT10 acetylates p53 at K120 and stabilizes p53 by counteracting Mdm2 action. In addition, NAT10 promotes Mdm2 degradation with its intrinsic E3 ligase activity.

SIGNOR-272406

P07101

O75582

0

phosphorylation

up-regulates

0.337

Recombinant human tyrosine hydroxylase (hth1) was found to be phosphorylated by mitogen and stress-activated protein kinase 1 (msk1) at ser40 and by p38 regulated/activated kinase (prak) on ser19. Phosphorylation by msk1 induced an increase in vmax. studies on th from several species suggest that ser40 is the main site involved in direct activation of th

SIGNOR-95491

Q9BUR4

Q13315

0

phosphorylation

up-regulates activity

0.337

Here, we show that in response to various types of DNA damage, including IR and UV, WRAP53β is phosphorylated on serine residue 64 by ATM with a time-course that parallels its accumulation at DNA lesions. Interestingly, recruitment of phosphorylated WRAP53β (pWRAP53βS64) to sites of such DNA damage promotes its interaction with γH2AX at these locations.

SIGNOR-273511

P01106

Q01196

0

transcriptional regulation

down-regulates quantity by repression

0.337

RUNX1 represses MYC expression through direct binding at three downstream enhancer elements

SIGNOR-260093

P01236

Q13177

0

phosphorylation

up-regulates

0.337

Phosphorylated form of prolactin has a higher affinity for heparin.

SIGNOR-186211

P04818

P01106

0

transcriptional regulation

up-regulates quantity by expression

0.337

Analysis of in vivo C-MYC interactions with TS, IMPDH2 and PRPS2 genes confirmed that they are direct C-MYC targets. C-MYC depletion did not significantly affect levels of E2F1 protein reported to regulate expression of many S-phase specific genes, but resulted in the repression of several genes encoding enzymes rate-limiting for dNTP metabolism. These included thymidylate synthase (TS), inosine monophosphate dehydrogenase 2 (IMPDH2) and phosphoribosyl pyrophosphate synthetase 2 (PRPS2). C-MYC depletion also resulted in reduction in the amounts of deoxyribonucleoside triphosphates (dNTPs) and inhibition of proliferation.

SIGNOR-267374

P20226

Q7Z6Z7

0

ubiquitination

down-regulates quantity

0.337

Having established that Huwe1 mediates TBP ubiquitination in vitro, we then asked which E2 conjugating enzymes work best with Huwe1 in this reaction.|Upregulation of Huwe1 expression during myogenesis induces TBP degradation and myotube differentiation.

SIGNOR-278696

Q8N752

A6ND36

0

binding

up-regulates quantity

0.337

We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.

SIGNOR-273753

P30086

Q00535

0

phosphorylation

down-regulates quantity by destabilization

0.337

Here, we demonstrate that RKIP is a substrate of cyclin-dependent kinase 5 (CDK5) in neurons and that the phosphorylation of RKIP at T42 causes the release of Raf-1. Moreover, T42 phosphorylation promotes the exposure and recognition of the target motif "KLYEQ" in the C-terminus of RKIP by chaperone Hsc70 and the subsequent degradation of RKIP via chaperone-mediated autophagy (CMA).

SIGNOR-276672

P12755

P31749

0

phosphorylation

down-regulates

0.337

The phosphorylation of ski at threonine 458 is induced by akt pathway activators including insulin, insulin-like growth factor-1, and hepatocyte growth factor. The phosphorylation of ski causes its destabilization and reduces ski-mediated inhibition of expression of another negative regulator of tgf-beta, smad7

SIGNOR-252527

P48775

P04150

0

transcriptional regulation

down-regulates quantity by repression

0.337

Repression of GR-mediated expression of the tryptophan oxygenase gene by the SWI/SNF complex during liver development.

SIGNOR-268995

P84022

P78368

0

phosphorylation

down-regulates

0.337

Cki?2 Directly phosphorylates smad3 at ser418, leading to the increased ubiquitination and proteasomal degradation of activated smad3 following tgf-? Treatment.

SIGNOR-181069

Q15078

P15882

0

binding

up-regulates

0.337

_-chimaerin was identified to interact with the p35 activator of cdk5. The complex of _-chimaerin, cdk5 and p35 is enzymatically functional

SIGNOR-123439

Q9UNH5

Q7Z569

0

polyubiquitination

up-regulates activity

0.337

Brap2 promotes Lys-63 linked ubiquitination of HsCdc14A. Collectively, these results support the idea that Brap2 facilitates Lys-63 linked ubiquitin modification of HsCdc14A, which may not be targeted for degradation, but mainly for protein–protein interactions or other regulatory functions.

SIGNOR-271777

Q13153

P27361

0

phosphorylation

down-regulates

0.337

Activated erk can phosphorylate t292 in the prs, and this blocks the ability of pak to phosphorylate s298 and of rac-pak signaling to enhance mek1-erk complex formation.

SIGNOR-123074

P15509

P09603

0

binding

up-regulates

0.337

Granulocyte-macrophage colony-stimulating factor (gm-csf) is an important hematopoietic cytokine that exerts its effects by interaction with the gm-csf receptor (gmr) on the surface of responsive cells. The gm-csf receptor consists of two subunits: gmralpha, which binds gm-csf with low affinity, and gmrbeta, which lacks intrinsic ligand-binding capability but complexes with gmralpha to form a high-affinity receptor (gmralpha/beta).

SIGNOR-72455

Q16584

P49841

0

phosphorylation

up-regulates activity

0.336

Further, investigation revealed that MLK3 was phosphorylated at two residues Ser789 and Ser793 by GSK3\u03b2 ( xref ).|When, these two sites on MLK3 were mutated to non-phosphorable Ala, the activation of MLK3 by GSK3\u03b2 was blocked, and neuronal cell death upon NGF withdrawal also prevented ( xref ).

SIGNOR-279615

Q99640

P45983

0

phosphorylation

up-regulates

0.336

A kinase assay using gst-myt1 revealed that active jnk1 or jnk3, but not jnk2, phosphorylated myt1 in vitro.

SIGNOR-183899

P78357

P12931

0

phosphorylation

down-regulates activity

0.336

If that is the case, then our genetic results support the notion that p190 is negatively regulated by both Src and integrin.|The Src family of tyrosine kinases phosphorylate mammalian p190.

SIGNOR-279572

Q9UQ80

P35637

0

sumoylation

up-regulates activity

0.336

Here, we show that Ebp1 p42 isoform can be sumoylated on both K93 and K298 residues, which mediate its nuclear translocation and are required for its anti-proliferative activity .. Hence, TLS-mediated sumoylation is required for Ebp1 transcriptional repressive activity.

SIGNOR-236904

P01584

Q16665

0

transcriptional regulation

up-regulates quantity by expression

0.336

We finally confirmed that in the absence of HIF-1α there was a significant reduction at the protein level in pro-caspase-1, activated caspase-1, pro-IL-1β, and ultimately active IL-1β (Fig. 4g and h). These data show that adenosine induced up-regulation of IL-1β is dependent on a CREB/HIF-1α pathway which is distinct from the NF-kB pathway used for initial production of IL-1β in response to LPS.

SIGNOR-251718

Q9BT92

Q8N5Z5

0

binding

down-regulates quantity by destabilization

0.336

We have identified KCTD17 as a substrate-adaptor for Cul3-RING E3 ligases (CRL3s) that polyubiquitylates trichoplein. Depletion of KCTD17 specifically arrests ciliogenesis at the initial step of axoneme extension through aberrant trichoplein-Aurora-A activity. Thus, CRL3-KCTD17 targets trichoplein to proteolysis to initiate the axoneme extension during ciliogenesis.

SIGNOR-272463

P00533

P10586

0

dephosphorylation

down-regulates activity

0.336

Some 10 years ago, Hashimoto et al. (87) had shown that the LAR catalytic domain can dephosphorylate the EGFR receptor in vitro, and more recently, Kulas and colleagues (88) have demonstrated that the antisense mediated suppression of LAR can enhance the growth factor induced activation of EGFR in rat hepatoma cells.|These data indicate that LAR and RPTPsigma may have a significant role in GPCR induced EGFR signalling.Whereas in A431 cells LAR and RPTPsigma may act to suppress the EGFR in response to GPCR activation, it is possible that the converse may also be true in other cell types.

SIGNOR-277029

O15350

O15111

0

phosphorylation

up-regulates activity

0.336

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

SIGNOR-279697

Q01094

Q13490

0

ubiquitination

up-regulates activity

0.336

The ability of cIAP1 to promote wt E2F1 transcriptional activity was retained by all E2F1 mutants, except the K161R/164R mutant for which cIAP1 was completely inactive and the K185R whose basal transactivation activity was weakly enhanced by cIAP1 (XREF_FIG).|Here, we demonstrated that the E3-ubiquitin ligase cellular inhibitor of apoptosis 1 (cIAP1) increases E2F1 K63-poly-ubiquitination on the lysine residue 161/164 cluster, which is associated with the transcriptional factor stability and activity.

SIGNOR-278688

Q14790

Q5T447

0

polyubiquitination

down-regulates activity

0.336

HECTD3, a new E3 ubiquitin ligase, interacts with caspase-8 death effector domains and ubiquitinates caspase-8 with K63-linked polyubiquitin chains that do not target caspase-8 for degradation but decrease the caspase-8 activation. HECTD3 ubiquitinates caspase-8 with K63-linked polyubiquitin chains at K215.

SIGNOR-272077

P04637

P51812

0

phosphorylation

up-regulates activity

0.336

Here we show that ribosomal S6 kinase 2 (RSK2) activates and phosphorylates p53 (Ser15) in vitro and in vivo and colocalizes with p53 in the nucleus.

SIGNOR-279567

Q04721

Q4G148

0

binding

up-regulates

0.336

We have previously identified two human genes, gxylt1 and gxylt2, encoding glucoside xylosyltransferases responsible for the transfer of xylose to o-linked glucose. The identity of the enzyme further elongating the glycan to generate the final trisaccharide xylose-xylose-glucose, however, remained unknown. Here, we describe that the human gene c3orf21 encodes a udp-xylose:alfa-xyloside alfa1,3-xylosyltransferase, acting on xylose-alfa1,3-glucosebeta1-containing acceptor structures. We have, therefore, renamed it xxylt1 (xyloside xylosyltransferase 1). Xxylt1 cannot act on a synthetic acceptor containing an alfa-linked xylose alone, but requires the presence of the underlying glucose. Activity on notch egf repeats was proven by in vitro xylosylation of a mouse notch1 fragment recombinantly produced in sf9 insect cells, a bacterially expressed egf repeat from mouse notch2 modified in vitro by rumi and gxylt2 and in vivo by co-expression of the enzyme with the notch1 fragment. The enzyme was shown to be a typical type ii membrane-bound glycosyltransferase localized in the endoplasmic reticulum.

SIGNOR-177694

P11473

P68400

0

phosphorylation

up-regulates

0.336

Casein kinase ii (ckii) phosphorylates vdr both in vitro and in vivo at serine 208 within the hinge domain. This phosphorylation does not affect the ability of vdr to bind dna, but increases its ability to transactivate target promoters

SIGNOR-153711

P01112

Q8TEU7

0

guanine nucleotide exchange factor

up-regulates

0.336

Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.

SIGNOR-183796

P50148

P07550

0

binding

up-regulates activity

0.336

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

SIGNOR-257081

Q8IXH7

P12931

0

phosphorylation

down-regulates activity

0.336

Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of TH1 at Tyr-6 in vivo and in vitro. Phosphorylation of TH1 decreases its association with A-Raf and PAK1.

SIGNOR-276402

Q9UM54

O75914

0

phosphorylation

up-regulates activity

0.336

P21-activated kinase 3 phosphorylated myosin VI, and the site was identified as Thr(406). The phosphorylation of myosin VI significantly facilitated the actin-translocating activity of myosin VI.

SIGNOR-250244

P15941

Q05655

0

phosphorylation

up-regulates

0.336

We show that phosphorylation of muc1 by pkcdelta increases binding of muc1 and beta-catenin in vitro and in vivo. The functional significance of the muc1-pkcdelta interaction is further supported by the demonstration that mutation of the pkcdelta phosphorylation site abrogates muc1-mediated decreases in binding of beta-catenin to e-cadherin

SIGNOR-115501

O43504

Q13315

0

phosphorylation

up-regulates activity

0.336

Strikingly, we found that the kinase ataxia telangiectasia mutated (ATM) phosphorylated HBXIP at Ser (108).|The knockdown of ATM by siRNA remarkably decreased the levels of serine phosphorylation and blocked the nuclear import of HBXIP.

SIGNOR-279791

Q01105

P48736

0

phosphorylation

up-regulates activity

0.336

We show that PI3Kgamma phosphorylates I2PP2A on serine 9 and 93 residues resulting in enhanced interaction of I2PP2A with PP2A.

SIGNOR-278320

Q9UM11

Q86T82

0

binding

down-regulates activity

0.336

Here we show that USP37 binds the APC/C coactivator CDH1|Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry

SIGNOR-265054

P06400

Q00535

0

phosphorylation

down-regulates

0.336

Phosphorylation was observed 6 hours after p25 induction and was abolished in the presence of a cdk5 inhibitor, roscovitine, which does not inhibit the usual rb cyclin-d kinases cdk4 and cdk6. Furthermore, analyses of levels and subcellular localization of cdk-related cyclins did not reveal any change following cdk5 activation, arguing for a direct effect of cdk5 activity on rb protein. Rb phosphorylation was visualized using phosphorylation-dependent antibodies (p-rbser795 and p-rbser807/811).

SIGNOR-134468