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
Q13526	P53355	phosphorylation	down-regulates activity	0.369	DAPK1 inhibits Pin1 nuclear localization and cellular function.\|DAPK1 interacts with and phosphorylates Pin1 on Ser71 in vitro and in vivo.	SIGNOR-278160
O00192	Q9UDY2	relocalization	down-regulates activity	0.369	We identified ARVCF as a binding partner of ZO-1 and ZO-2 and characterized the role of PDZ-domain proteins in plasma membrane and nuclear localization of ARVCF. ZO-2, in contrast, relocated to the nucleus with ARVCF, and, given the interaction between the ZO-2 PDZ domains and ARVCF, raised the possibility that ZO-2 may play a role in nuclear localization of ARVCF. Such a role for ZO-2 is indeed supported by the ability of the ZO-2 PDZ domain to efficiently relocate ARVCF from the plasma membrane to the nucleus in a process that required the ability of the two proteins to interact and the presence of a functional NLS in the ZO-2 PDZ domains. Thus, ZO-2 could be involved in nuclear translocation and/or retention of ARVCF and play a role in regulating postulated functions of ARVCF in gene expression	SIGNOR-252122
Q9Y463	P28482	phosphorylation	up-regulates activity	0.369	S421 resides within a Ser-Pro phosphoacceptor motif that is typical for ERK1/2 and recombinant ERK2 phosphorylated DYRK1B at S421 in vitro.	SIGNOR-276937
P53778	Q13884	binding	down-regulates	0.368	Basal localization of the p38g/p-Carm1 complex in muscle stem cells occurs via binding to the dystrophin-glycoprotein complex (DGC) through b1-syntrophin. In dystrophin-deficient muscle stem cells undergoing asymmetric division, p38g/b1-syntrophin interactions are abrogated, resulting in enhanced Carm1 phosphorylation	SIGNOR-255901
P31946	Q05513	phosphorylation	down-regulates activity	0.368	Our results with the 14-3-3 mutants indirectly imply a new phosphorylation site, 130Ser (and to a lesser extent 141Thr), in 14-3-3b that regulates the association}dissociation of 14-3-3b and PKC-f.	SIGNOR-249035
P12036	P28482	phosphorylation	up-regulates activity	0.368	The fraction containing Erk2, as well as bacterially expressed Erk1 and Erk2, phosphorylated all types of KSP motifs in peptides (KSPXK, KSPXXK, KSPXXXK, and KSPXXXXK) derived from NF-M and NF-H. They also phosphorylated an expressed 24 KSPXXXK repeat NF-H polypeptide, an expressed NF-H as well as dephosphorylated native rat NF-H, and NF-M proteins with accompanying decreases in their respective electrophoretic mobilities. \|Our data on primary hippocampal cells also showed an inhibition of neurite outgrowth by the drug that was accompanied by inhibition of MAP, NF-H, and NF-M phosphorylation.	SIGNOR-249424
O00418	P06493	phosphorylation	down-regulates	0.368	Phosphorylation at ser359 inhibits eef2k activity even at high calcium concentrations. we demonstrate that cdc2 contributes to controlling eef2 phosphorylation in cells. inactivation of eef2k by cdc2 may serve to keep eef2 active during mitosis	SIGNOR-177982
Q96GG9	P46934	monoubiquitination	up-regulates quantity	0.368	Here we revealed a previously unknown mechanism that regulates hDCNL1. In cultured mammalian cells ectopically expressed hDCNL1 was mono-ubiquitinated predominantly at K143, K149, and K171. Using a classical chromatographic purification strategy, we identified Nedd4-1 as an E3 ligase that can catalyze mono-ubiquitination of hDCNL1 in a reconstituted ubiquitination system.Taken together, these results suggest a mono-ubiquitination-mediated mechanism that governs nuclear-cytoplasmic trafficking of hDCNL1,	SIGNOR-272719
Q92900	Q13535	phosphorylation	up-regulates activity	0.368	Phosphorylation of UPF1 by the PIKKs SMG1, ATM and ATR is stimulated in response to DNA damage.	SIGNOR-278911
Q13144	P49840	phosphorylation	down-regulates activity	0.368	We identify multiple phosphorylation sites in the largest, catalytic, subunit (epsilon) of mammalian eIF2B. Glycogen synthase kinase 3 (GSK3) is responsible for phosphorylating Ser535. This regulatory phosphorylation event requires both the fourth site (Ser539) and a distal region, which acts to recruit GSK3 to eIF2Bepsilon in vivo. eIF2Bϵ from mammals or insects is a substrate for glycogen synthase kinase 3 (GSK3), and this inhibits the activity of eIF2B	SIGNOR-251215
O43524	Q13547	deacetylation	up-regulates activity	0.368	The ability of HDAC1 to cause muscle atrophy required its deacetylase activity and was linked to the induction of several atrophy genes by HDAC1, including atrogin-1, which required deacetylation of FoxO3a	SIGNOR-256486
Q13043	Q7L7X3	phosphorylation	up-regulates	0.368	In addition, the thousand-and-one (tao) amino acids kinase or taok13 has been shown to directly phosphorylate and activate hpo or mst1/2.	SIGNOR-201324
Q6STE5	Q16539	phosphorylation	up-regulates activity	0.368	P38 phosphorylates the baf60 subunit of the swi-snf chromatin remodelling complex, and p38 recruits this complex to differentiation-specific loci.	SIGNOR-176557
Q9H211	P45983	phosphorylation	up-regulates quantity by stabilization	0.368	We discovered that human Cdt1, an essential origin licensing protein whose activity must be restricted to G(1) phase, is a substrate of the stress-activated mitogen-activated protein (MAP) kinases p38 and c-Jun N-terminal kinase (JNK). These MAP kinases phosphorylate Cdt1 both during unperturbed G(2) phase and during an acute stress response. Phosphorylation renders Cdt1 resistant to ubiquitin-mediated degradation during S phase and after DNA damage by blocking Cdt1 binding to the Cul4 adaptor, Cdt2.	SIGNOR-276361
P08922	P29350	dephosphorylation	down-regulates	0.368	Overexpression of shp-1 results in ros dephosphorylation and effectively downregulates ros-dependent proliferation and transformation. We propose that shp-1 is an important downstream regulator of ros signaling.	SIGNOR-105922
P17612	O00408	binding	down-regulates activity	0.368	We show that caffeine, by inhibiting PDE2, enhances PKA phosphorylation leading to mitochondrial NCLX activation, thereby reducing neuronal excitotoxicity and enhancing learning in mice.	SIGNOR-275730
O14965	O94889	binding	up-regulates activity	0.368	We identify Aurora-A as a KLHL18-interacting partner. Overexpression of KLHL18 and CUL3 promotes Aurora-A ubiquitylation in vivo, and the CUL3-KLHL18-ROC1 ligase ubiquitylates Aurora-A in vitro. Our study reveals that the CUL3-KLHL18 ligase is required for timely entry into mitosis, as well as for the activation of Aurora-A at centrosomes.We also noticed that overexpression of both CUL3 and KLHL18 stimulated mono-ubiquitylation of Aurora-A as well (Fig. 8A,B).	SIGNOR-272021
P45973	P68400	phosphorylation	up-regulates	0.368	Hp1_ was multiply phosphorylated at n-terminal serine residues (s11-14) in human and mouse cells and that this phosphorylation enhanced hp1_'s affinity for h3k9me. Unphosphorylatable mutant hp1_ exhibited severe heterochromatin localization defects in vivo, and its prolonged expression led to increased chromosomal instability.	SIGNOR-171707
Q9Y6Q9	P06493	phosphorylation	down-regulates	0.368	We demonstrate that aib1 is phosphorylated on ser728 and ser867 by cdk1/cyclin b at the onset of mitosis and remains phosphorylated until exit from m phase.	SIGNOR-195233
P60880	Q9ULU8	binding	up-regulates activity	0.368	CAPS interacted independently with either syntaxin-1 or SNAP-25 suggesting that CAPS might promote QaQbc-SNARE heterodimer formation. CAPS binding to syntaxin-1 was mediated by the membrane-proximal C-terminal SNARE motif (H3) and membrane linker domain sequences of syntaxin-1	SIGNOR-264338
P48736	P10747	binding	up-regulates	0.368	Cd28 can bind directly to pi3k by a well-characterized ymnm binding motif in its cytoplasmic domain.	SIGNOR-159322
P07101	P17612	phosphorylation	up-regulates activity	0.368	HTH1 was phosphorylated at Ser40 by PKA. Tyrosine hydroxylase (TH) has been reported to require binding of 14-3-3 proteins for optimal activation by phosphorylation. phosphorylationof hTH1‚4 at Ser40, to a stoichiometry of up to 1.0 molphosphate per mol TH subunit, dramatically increases their binding to 14-3-3 proteins.	SIGNOR-250061
P62633	Q99873	methylation	down-regulates	0.368	Cnbp interacts with protein arginine methyltransferase prmt1 / r25 or r27 appear to be the major methylation sites in cnbp /arginine methylation of cnbp impedes rna binding	SIGNOR-204958
O15525	P27361	phosphorylation	up-regulates quantity	0.368	By contrast, MAFG-S124A was not phosphorylated, indicating that ERK1 phosphorylates MAFG at S124.\|Notably, cotransfection of ERK1 increased total levels of wild-type MAFG and MAFG-T3A but not MAFG-S124A, indicating that phosphorylation increased MAFG stability.	SIGNOR-280027
P12931	Q8WTV0	binding	up-regulates activity	0.368	Importantly, coimmunoprecipitation of SR-BI and Src demonstrated that the two proteins are directly associated in WT macrophages (Fig. 7B), suggesting that SR-BI plays a direct role in activation of Src in macrophages.	SIGNOR-260314
P11274	P07332	phosphorylation	down-regulates activity	0.368	In the present study, we demonstrate that BCR Tyr-246 and at least one of the closely spaced tyrosine residues, Tyr-279, Tyr-283, and Tyr-289 (3Y cluster), are phosphorylated by FES both in vitro and in 32Pi-labeled cells. Co-expression of BCR and FES in human 293T cells stimulated the tyrosine autophosphorylation of FES. By contrast, tyrosine phosphorylation of BCR by FES suppressed BCR serine/threonine kinase activity toward the 14-3-3 protein and BCR substrate, BAP-1.	SIGNOR-251137
Q96FE7	P39880	transcriptional regulation	down-regulates quantity by repression	0.368	We demonstrate that CUX1 deficiency activates phosphoinositide 3-kinase (PI3K) signaling through direct transcriptional downregulation of the PI3K inhibitor PIK3IP1 (phosphoinositide-3-kinase interacting protein 1), leading to increased tumor growth and susceptibility to PI3K-AKT inhibition.	SIGNOR-260072
P49768	Q14790	cleavage	up-regulates activity	0.368	Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.	SIGNOR-261760
Q9UI46	Q92949	transcriptional regulation	up-regulates quantity by expression	0.368	FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).	SIGNOR-266932
P25490	Q96GD4	phosphorylation	up-regulates	0.368	Aurora b kinase phosphorylates yy1 on serine 184 and to a lesser extent serine 180 at the g2/m stage of the cell cycle (fig. 7). We show that yy1 is rapidly dephosphorylated as the cells exit mitosis, likely by pp1. Also, our data indicates that phosphorylation at serine 180 and serine 184 can affect the dna binding activity of yy1	SIGNOR-200079
P00533	Q05655	phosphorylation	down-regulates activity	0.368	These data indicate that activation of protein kinase C and subsequent phosphorylation of the EGF receptor at T654 lead to rapid physiological attenuation of EGF receptor signaling.	SIGNOR-248858
Q13887	P49841	phosphorylation	down-regulates	0.368	Stability of the klf5 is mediated by proteasomal degradation via phosphorylation by glycogen synthase kinase 3_ (gsk3_) and recognition by f-box and wd repeat domain-containing 7 (fbw7) of a phosphodegron sequence surrounding serine 303 in klf5	SIGNOR-203627
P11831	O43474	binding	down-regulates	0.368	Klf4 antagonizes contractile gene expression through diverse mechanisms including (i) inhibiting the binding of srf-myocd or srf-mrtfs to the carg box by direct association with srf.	SIGNOR-174258
P25963	P51812	phosphorylation	down-regulates quantity by destabilization	0.368	Here, we show that RSK2 is activated by treatment with tumor necrosis factor-alpha (TNF-alpha) and directly phosphorylates IkappaBalpha at Ser 32, leading to IkappaBalpha degradation.	SIGNOR-279108
P15498	P12931	phosphorylation	up-regulates activity	0.368	These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module.\|These interactions are required for SRC-induced tyrosine phosphorylation and activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module ( xref ).	SIGNOR-279124
Q05469	P28482	phosphorylation	up-regulates activity	0.368	Thus, activation of the ERK pathway appears to be able to regulate adipocyte lipolysis by phosphorylating HSL on Ser(600) and increasing the activity of HSL.	SIGNOR-249413
O14939	Q00535	phosphorylation	up-regulates activity	0.368	In this study, we suggest that the phosphorylation and activation of PLD2 by cyclin-dependent kinase 5 (Cdk5) is critical for EGF-dependent insulin secretion.\|We determined that Cdk5 phosphorylates PLD2 at Ser 134 of PLD2 and that this phosphorylation was suggested to be important for EGF-dependent insulin secretion.	SIGNOR-278395
P12830	P06493	phosphorylation	up-regulates activity	0.368	We show that adequate accumulation of Cin8 and Kip1 requires inactivation of the anaphase promoting complex-activator Cdh1 through sequential phosphorylation by Cdk1 and polo kinase.\|We show that adequate accumulation of Cin8 and Kip1 requires inactivation of the anaphase-promoting complex-activator Cdh1 through sequential phosphorylation by Cdk1 and polo kinase.	SIGNOR-280204
P23396	P31749	phosphorylation	up-regulates activity	0.368	Here, we show that human RPS3 is a physiological target of Akt kinase and a novel mediator of neuronal apoptosis. NGF stimulation resulted in phosphorylation of threonine 70 of RPS3 by Akt, and this phosphorylation was required for Akt binding to RPS3.our experiment demonstrated that Akt up-regulates the endonuclease activity of RPS3 via phosphorylation and led us to believe that Akt phosphorylation of RPS3 after DNA damage is an antiapoptotic signal or a molecular switch that extends the life of a cell after DNA damage.	SIGNOR-259815
P07949	Q9ULV8	ubiquitination	down-regulates quantity by destabilization	0.368	Here we show that Cbl-c binds wild-type and MEN2A isoforms of the receptor tyrosine kinase, RET, and that Cbl-c enhances ubiquitination and degradation of activated RET.\|We show that Cbl-c negatively regulates RET by ubiquitinating and downregulating the activated RTK while Enigma positively regulates activated RET by preventing Cbl-c binding to RET and thus preventing RET ubiquitination and degradation while promoting RET mitogenic signaling.	SIGNOR-278674
Q6P1J9	Q13882	phosphorylation	down-regulates activity	0.368	PTK6 impairs the coactivator function of parafibromin.\|To study the functional consequence of parafibromin phosphorylation by PTK6, we examined the effect of PTK6 inhibition on Wnt signal activation.	SIGNOR-279273
Q13332	Q96NI6	binding	up-regulates activity	0.368	SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development. we identified LAR-RPTPs as novel ligands of SALM5 that mediates SALM5-dependent presynaptic differentiation in a splicing-dependent manner. Our data indicate that SALM5 interacts with all three known LAR-RPTPs—LAR, PTPδ, and PTPσ (Fig. 1).	SIGNOR-264088
P46527	Q8TAS1	phosphorylation	up-regulates	0.367	Hkis is a nuclear protein that binds the c-terminal domain of p27(kip1) and phosphorylates it on s10 in vitro and in vivo, promoting its nuclear export to the cytoplasm.Phosphorylation at serine 10, a major phosphorylation site of p27(kip1), increases its protein stability	SIGNOR-90274
Q99683	Q06124	dephosphorylation	up-regulates	0.367	Previously we have shown that tyrosine 718 of ask1 when phosphorylated is critical for socs1 binding and socs1-mediated degradation of ask1we identified jak2 and shp2 as a tyr-718-specific kinase and phosphatase, respectively.	SIGNOR-184604
Q13813	O15287	null	up-regulates quantity by stabilization	0.367	In FA cells, deficiencies in FA proteins lead to decreased stability of alphaRIISp \|These results demonstrate that one of the FA proteins, FANCG, contains a motif that interacts directly with the SH3 domain of alphaIISp. We propose that this binding of FANCG to alphaIISp may be important for the stability of alphaIISp in cells and the role alphaIISp plays in the DNA repair process.\|	SIGNOR-263275
Q15700	P06241	phosphorylation	up-regulates activity	0.367	Recombinant PSD-93 was phosphorylated by Fyn in vitro, and Tyr-384 was identified as a major phosphorylation site. In COS7 cells, exogenously expressed PSD-93 was phosphorylated, dependent on its membrane localization. In addition, tyrosine-phosphorylated PSD-93 was able to bind to Csk, a negative regulator of Src family kinases, in vitro as well as in a brain lysate.	SIGNOR-262874
Q9NZV8	P28482	phosphorylation	up-regulates activity	0.367	We determined that the Kv4.2 C-terminal cytoplasmic domain is an effective ERK2 substrate, and that it is phosphorylated at three sites: Thr(602), Thr(607), and Ser(616). Phosphorylation of the Kv4.2 channel by ERK during LTP induction may lead to increased excitability and membrane depolarization of neurons, which would increase the magnitude of the calcium influx and the probability of triggering LTP.	SIGNOR-262935
P63000	Q8IYU2	ubiquitination	down-regulates quantity by destabilization	0.367	The CNF1 toxin of pathogenic Escherichia coli addresses Rac1 to ubiquitin-proteasome system (UPS). We report the essential role of the tumor suppressor HACE1, a HECT-domain containing E3 ubiquitin-ligase, in the targeting of Rac1 to UPS. HACE1 binds preferentially GTP-bound Rac1 and catalyzes its polyubiquitylation	SIGNOR-255538
Q9UK53	P12931	phosphorylation	down-regulates activity	0.367	Src Decreases the Stability and Level of ING1.\|This study, as well as a previous report identifying Ser-126 of ING1 as a kinase target, confirm that ING1 stability is also regulated by phosphorylation. However, the mechanism may be complex since phosphorylation of Ser-126 stabilizes the protein while phosphorylation by Src reduces ING1 stability and causes a relocalization of ING1 from the nucleus to the cytoplasm.	SIGNOR-279760
P46459	Q5S007	phosphorylation	up-regulates activity	0.367	LRRK2 phosphorylates full-length NSF at threonine 645 in the ATP binding pocket of D2 domain. Functionally, NSF phosphorylated by LRRK2 displays enhanced ATPase activity and increased rate of SNARE complex disassembling.	SIGNOR-277196
P40763	Q14526	binding	down-regulates quantity by repression	0.367	HIC1 interacts with the DNA binding domain of STAT3 and suppresses the binding of STAT3 to its target gene promoters. HIC1 C-terminal domain binds to STAT3. HIC1 mutant defective in STAT3 interaction reduced its repressive effect on STAT3 DNA binding activity, the reporter activity and gene expression of the VEGF and c-Myc genes, and cell growth in MDA-MB 231 cells.	SIGNOR-254246
Q12906	P31749	phosphorylation	up-regulates activity	0.367	Upon T cell activation, NF90 translocates from the nucleus into the cytoplasm, where it binds to the AU-rich element-containing 3' untranslated regions of IL-2 mRNA and stabilizes it.\|Our previous work showed that CD28 costimulation of T cells activated AKT to phosphorylate NF90 at Ser647 and caused NF90 to undergo nuclear export and stabilize IL-2 mRNA.	SIGNOR-252512
Q01094	Q92466	binding	up-regulates	0.367	We show that ddb, a putative dna repair protein, associates with the activation domain of e2f1 / expression of ddb specifically stimulated e2f1-activated transcription	SIGNOR-54102
Q9Y6R4	P49841	binding	down-regulates	0.367	Gsk3beta binding to mekk4 blocks mekk4 dimerization that is required for mekk4 activation, effectively inhibiting mekk4 stimulation of the jnk and p38 mapk pathways	SIGNOR-157541
P22736	Q15349	phosphorylation	down-regulates activity	0.367	Phosphorylation of a residue in the DNA-binding region (Ser-350 of NGFI-B and 354 of Nur77) has been described in detail to have effect on the transcriptional function of the protein [11, 24]. Growth-related kinase pp90rsk, but not ERK1 (pp44mapk), was shown to phosphorylate recombinant Nur77 in vitro in the DNA binding domain, but not the amino-terminus, using an immune complex kinase as- say [11].	SIGNOR-249429
Q13501	Q05655	phosphorylation	up-regulates activity	0.367	Data presented here suggested that Vps34 stimulates tumor development mainly through PKC-\u03b4- activation of p62.\|In conclusion, elevation of Vps34 results in tumor progression via the PKC-\u03b4-phosphorylation of p62 at S349 and PKC-\u03b4 involved phosphorylation of Raf 1 at Y340/341.\|Vps34 induces PKC-\u03b4-dependent phosphorylation of p62.	SIGNOR-280086
P15173	Q96NX9	transcriptional regulation	down-regulates quantity by repression	0.367	We confirmed Dach2 is a Mgn transcriptional repressor that mediates HDAC-dependent regulation by (i) overexpressing Dach2 in myotubes harboring the 133-bp Mgn promoter and (ii) rescuing TSA-mediated Mgn repression by Dach2 knockdown.	SIGNOR-261579
P23443	Q9HC98	phosphorylation	up-regulates activity	0.367	Here we demonstrate that in addition to phosphorylating S6K1 and SGK1 at their hydrophobic motif, NEK6 also phosphorylates S6K1 at two other sites and phosphorylates SGK1 at one other site in vitro. Analysis of the peptides phosphorylated by NEK6 (Fig 2), performed in the present study has confirmed this, and identified two novel sites on S6K1 (Ser53 and Ser403) as major sites of NEK6 phosphorylation.	SIGNOR-262953
Q92993	P49841	phosphorylation	up-regulates	0.367	We demonstrate that gsk-3 phosphorylates serine 86 of the p53-acetyltransferase tip60. A tip60(s86a) mutant was less active to induce p53 k120 acetylation, histone 4 acetylation, and expression of puma	SIGNOR-174049
P41235	P54646	phosphorylation	down-regulates quantity by destabilization	0.367	AMPK directly phosphorylates HNF4alpha and represses its transcriptional activity. AMPK-mediated phosphorylation of HNF4alpha on serine 304 had a 2-fold effect, reducing the ability of the transcription factor to form homodimers and bind DNA and increasing its degradation rate in vivo. Phosphorylation of HNF4α on Ser-304 reduces protein stability.	SIGNOR-250322
Q99683	O60674	phosphorylation	down-regulates quantity by destabilization	0.367	Furthermore, JAK2, but not JAK1, directly bound to and phosphorylated ASK1 at Tyr-718, leading to an enhanced association of ASK1 with SOCS1 and subsequent ASK1 degradation.	SIGNOR-276145
Q13043	P67775	dephosphorylation	down-regulates	0.367	Rassf1a apparently protects mst1/2 against inactivation by pp2a , the phosphatases that dephosphorylate the stimulatory thr-183 and thr-180 of mst1 andmst2, respectively.	SIGNOR-201270
P35712	P63279	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
O75444	P35452	binding	down-regulates activity	0.367	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-221887
P46531	Q13233	phosphorylation	down-regulates activity	0.367	As a result, MEKK1 suppresses the Notch1 intracellular domain protein stability and transcriptional activity.\|We confirmed that MEKK1 binds to Notch1 intracellular domain and phosphorylates the Notch1 intracellular domain Threonine 2512 residue.	SIGNOR-279628
Q70Z35	Q13153	phosphorylation	down-regulates activity	0.367	P21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase. PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ.	SIGNOR-277181
Q16204	Q969H0	binding	down-regulates	0.367	Fbxw7 interacts with and targets ccdc6 for ubiquitin-mediated proteasomal degradation	SIGNOR-199279
Q8IZL8	P24941	phosphorylation	up-regulates	0.367	We identified ser(477) and ser(991) of pelp1 as cdk phosphorylation sites. we conclude that pelp1 is a novel substrate of interphase cdks and that its phosphorylation is important for the proper function of pelp1 in modulating hormone-driven cell cycle progression and also for optimal e2f transactivation function.	SIGNOR-167766
Q9NRH2	Q15831	phosphorylation	up-regulates activity	0.367	We demonstrate that LKB1 activates SNRK by phosphorylating the T‐loop residue (Thr173)	SIGNOR-260824
Q9BXM7	Q7KZI7	phosphorylation	up-regulates activity	0.367	MARK2 phosphorylated and activated the cleaved form of PINK1 (DeltaN-PINK1	SIGNOR-278975
Q13950	Q16539	phosphorylation	up-regulates activity	0.367	Mechanistic analysis revealed that the TAK1–MKK3/6–p38 MAPK axis phosphorylated Runx2, promoting its association with the coactivator CREB-binding protein (CBP), which was required to regulate osteoblast genetic programs. These findings reveal an in vivo function for p38β and establish that MAPK signaling is essential for bone formation in vivo.	SIGNOR-255777
P08670	Q13464	phosphorylation	down-regulates activity	0.367	We found that vimentin, the most widely expressed intermediate filament protein, served as an excellent substrate for Rho-associated kinase (Rho-kinase) and that vimentin phosphorylated by Rho-kinase lost its ability to form filaments in vitro. Two amino-terminal sites on vimentin, Ser38 and Ser71, were identified as the major phosphorylation sites for Rho-kinase, and Ser71 was the most favored and unique phosphorylation site for Rho-kinase in vitro.	SIGNOR-248998
Q53EZ4	P28482	phosphorylation	down-regulates	0.367	Upon mitotic entry, centrosome dissociation of cep55 is triggered by erk2/cdk1-dependent phosphorylation at s425 and s428. S425/428 phosphorylation is required for interaction with plk1, enabling phosphorylation of cep55 at s436. enabling it to relocate to the midbody to function in mitotic exit and cytokinesis.	SIGNOR-140890
P11532	Q12955	relocalization	up-regulates quantity	0.367	We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4.	SIGNOR-266715
Q16204	P27361	phosphorylation	up-regulates activity	0.367	We have characterized the H4(D10S170) gene product, showing that it is a ubiquitously expressed 55 KDa nuclear and cytosolic protein that is phosphorylated following serum stimulation. This phosphorylation was found to depend on mitogen-activated protein kinase (MAPK) Erk1/2 activity and to be associated to the relocation of H4(D10S170) from the nucleus to the cytosol. S244 is the major target residue of ERK1	SIGNOR-276003
P12259	P08246	cleavage	up-regulates activity	0.366	Human neutrophil elastase activates human factor V but inactivates thrombin-activated human factor V\|NH2-terminal sequence analysis of F.V treated with HNE indicated cleavage at Ile819 and Ile1484 under conditions during which the procofactor expressed enhanced cofactor activity in the prothrombinase complex.	SIGNOR-263637
P30304	Q15418	phosphorylation	down-regulates	0.366	Rsk promotes g2/m transition through activating phosphorylation of cdc25a and cdc25b rsk is likely to be more active in mitotic cells than in interphase cells, as evidenced by the phosphorylation status of t359/s363 in rsk. Together, these findings indicate that rsk promotes g2/m transition in mammalian cells through activating phosphorylation of cdc25a and cdc25b.	SIGNOR-202117
P14136	P17252	phosphorylation	down-regulates activity	0.366	Glial fibrillary acidic protein (GFAP), the intermediate filament component of astroglial cells, can serve as an excellent substrate for both cAMP-dependent protein kinase and protein kinase C, in vitro. GFAP phosphorylated by each protein kinase does not polymerize, and the filaments that do polymerize tend to depolymerize after phosphorylation. Dephosphorylation of phospho-GFAP by phosphatase led to a recovery of the polymerization competence of GFAP. Most of the phosphorylation sites for cAMP-dependent protein kinase and protein kinase C on GFAP are the same, Ser-8, Ser-13, and Ser-34. cAMP-dependent protein kinase has one additional phosphorylation site, Thr-7.	SIGNOR-248862
Q96QF0	Q15208	phosphorylation	up-regulates activity	0.366	We identified 5 potential NDR1 substrates in the mouse brain and chose two for functional validation. We show that one NDR1 substrate is another kinase, AP-2 associated kinase-1 (AAK1) which regulates dendritic branching as a result of NDR1 phosphorylation. Another substrate is the Rab8 guanine nucleotide exchange factor (GEF) Rabin8 (a Sec2p homolog) which we find is involved in spine synapse formation.	SIGNOR-263036
Q16760	P17252	phosphorylation	down-regulates activity	0.366	The plasma membrane translocation of diacylglycerol kinase delta1 is negatively regulated by conventional protein kinase C-dependent phosphorylation at Ser-22 and Ser-26 within the pleckstrin homology domain.	SIGNOR-249265
Q13285	P50613	phosphorylation	up-regulates	0.366	In conclusion, our results indicate that cdk7, as part of the cak complex and tfiih, phosphorylates sf1 at s203 followed by increased transcriptional activity of sf1	SIGNOR-157952
P00338	P11362	phosphorylation	up-regulates	0.366	We found that the oncogenic receptor tyrosine kinase fgfr1 directly phosphorylates ldh-a. Phosphorylation at y10 and y83 enhances ldh-a activity by enhancing the formation of active, tetrameric ldh-a and the binding of ldh-a substrate nadh, respectively.	SIGNOR-176730
P04637	Q9BV47	dephosphorylation	down-regulates activity	0.366	Dual-specificity phosphatase 26 is a novel p53 phosphatase and inhibits p53 tumor suppressor functions in human neuroblastoma\|Inhibiting DUSP26 expression in the IMR-32 neuroblastoma cell line enhanced doxorubicin-induced p53 phosphorylation at Ser20 and Ser37, p21, Puma, Bax expression as well as apoptosis	SIGNOR-248765
O95816	P49137	phosphorylation	up-regulates	0.366	We provided definite evidence that mapkapk2 phosphorylates bag2 at ser 20 in vitro and in vivo. These results demonstrate that bag2 is a novel component of the p38 mapk signaling pathways.	SIGNOR-126953
Q13233	P01116	binding	up-regulates	0.366	Mitogen-activated protein kinase kinase kinase (mekk1) is a serine-threonine kinase that regulates sequential protein kinase pathways involving stress-activated protein kinases and mitogen-activated protein kinases. Mekk1 is activated in response to growth factor stimulation of cells and by expression of activated ras. mekk1 directly binds ras.GTP. Thus, ras interacts with protein kinases of both the raf and mekk families.	SIGNOR-32620
P35712	Q00535	phosphorylation	down-regulates quantity	0.366	GST-Sox6 was phosphorylated in vitro by Cdk5 and p35 (XREF_FIG).\|Inhibition of Cdk5 activity by DN Cdk5 and roscovitine increases the Sox6 expression in primary cortical neurons.	SIGNOR-279365
P61204	Q9Y6D6	guanine nucleotide exchange factor	up-regulates activity	0.366	Brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) is an approximately 200-kDa brefeldin A-inhibited guanine nucleotide-exchange protein that preferentially activates ADP-ribosylation factor 1 (ARF1) and ARF3.	SIGNOR-272148
Q13224	Q96AX9	ubiquitination	down-regulates quantity	0.366	Mib2 is localized to the PSD of dendrites in hippocampal neurons and directly ubiquitinates GluN2B in a manner dependent on the non receptor tyrosine kinase Fyn.\|These findings suggest that Mib2 mediates proteasome dependent degradation of GluN2B subunits, which may provide a reciprocal mechanism to SCF Fbx2 regulation of GluN2A.	SIGNOR-278762
Q6UXI9	Q5H8C1	transcriptional regulation	up-regulates quantity by expression	0.366	The loss of QBRICK significantly diminished the expression of nephronectin, an integrin α8β1 ligand necessary for renal development. In vivo, nephronectin associated with QBRICK and localized at the sublamina densa region, where QBRICK was also located. Collectively, these findings indicate that QBRICK facilitates the integrin α8β1-dependent interactions of cells with basement membranes by regulating the basement membrane assembly of nephronectin and explain why renal defects occur in Fraser syndrome.	SIGNOR-253308
Q9GZV5	P48730	phosphorylation	down-regulates	0.366	LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP)	SIGNOR-234438
Q16623	P68400	phosphorylation	up-regulates	0.366	In this report, we show that syntaxin-1a is phosphorylated in vitro by cki on thr21. Casein kinase ii (ckii) has been shown previously to phosphorylate syntaxin-1a in vitro and we have identified ser14 as the ckii phosphorylation site. the phosphorylation of syntaxin-1a by ckii enhances its capacity to associate with synaptotagmin [21]. Therefore, phosphorylation of ser14 by ckii suggests an important role for this residue in regulating the interaction between syntaxin-1a and synaptotagmin	SIGNOR-114840
A5D8V6	Q9UHD2	phosphorylation	down-regulates activity	0.366	We have identified that TBK1 may target and phosphorylate VPS37C, a structural component of ESCRT-I complex, and serve as a ratelimiting factor in the control of PTAP-dependent (HIV-1, MLV/p6, and EIAV/PTAP), but not PPPY-dependent (MLV, EIAV/PPPY) retrovirus budding, independent of its role in IFN-I signaling.	SIGNOR-279768
Q13158	Q9BV47	dephosphorylation	down-regulates activity	0.366	This multi-functionality of fadd may depend primarily on its subcellular location. Fadd shuttles between the cytosol and the nucleus and this signal is unclear;however, fadd trafficking requires phosphorylation of the protein on ser194dusp26 suppresses cell proliferation by fadd dephosphorylation	SIGNOR-204559
Q09472	Q05655	phosphorylation	down-regulates	0.366	Inhibition of histone acetyltransferase function of p300 by pkcdeltawe found that pkcdelta but not classical pkc, specifically phosphorylates p300 at serine 89 in vitro and in vivo. This phosphorylation causes inhibition of p300 intrinsic hat activity.	SIGNOR-94263
P54274	Q96GD4	phosphorylation	up-regulates activity	0.366	Our data indicate that AURKB can phosphorylate the integral telomere DNA-binding Shelterin protein TERF1 at S404 (within the DNA-binding domain) in vitro .	SIGNOR-279440
Q9Y6X9	Q13153	phosphorylation	up-regulates activity	0.366	We demonstrate that PAK1-mediated MORC2 phosphorylation promotes cell cycle progression, defective phosphorylation of MORC2-S677A results in attenuated cell proliferation and tumorigenicity of gastric cancer cells, which is significantly enhanced in overexpression of phospho-mimic MORC2-S677E form, suggesting the importance of MORC2 phosphorylation in tumorigenesis.	SIGNOR-273714
Q8N726	Q9UHC7	polyubiquitination	down-regulates quantity by destabilization	0.366	Biochemical analyses confirmed that MKRN1 targets p14ARF for ubiquitination and subsequent proteasome-dependent degradation.The Skp1-Cul1-F-box-protein44 (SCF(FBXO44)) complex ubiquitinates full-length BRCA1 in vitro.	SIGNOR-272036
Q96J02	P06241	phosphorylation	down-regulates activity	0.366	Tyrosine phosphorylation of Itch appears to reduce its interaction with its substrate JunB. The turnover of JunB is accelerated in Fyn-deficient T cells, which is further reconstituted by Itch Tyr371 mutation	SIGNOR-245332
Q12913	P06241	phosphorylation	up-regulates activity	0.366	We demonstrate here that DEP-1 is phosphorylated in a Src- and Fyn-dependent manner on Y1311 and Y1320, which bind the Src SH2 domain. This allows DEP-1-catalyzed dephosphorylation of Src inhibitory Y529 and favors the VEGF-induced phosphorylation of Src substrates VE-cadherin and Cortactin.	SIGNOR-276372
Q9UDY8	Q5T447	polyubiquitination	up-regulates quantity by stabilization	0.366	HECTD3 promotes MALT1 ubiquitination with nondegradative polyubiquitin chains by direct interacting with the MALT1 through its N-terminal destruction of cyclin domain. HECTD3 does not target MALT1 for degradation but stabilize it.	SIGNOR-272096

Q13526

P53355

0

phosphorylation

down-regulates activity

0.369

DAPK1 inhibits Pin1 nuclear localization and cellular function.|DAPK1 interacts with and phosphorylates Pin1 on Ser71 in vitro and in vivo.

SIGNOR-278160

O00192

Q9UDY2

0

relocalization

down-regulates activity

0.369

We identified ARVCF as a binding partner of ZO-1 and ZO-2 and characterized the role of PDZ-domain proteins in plasma membrane and nuclear localization of ARVCF. ZO-2, in contrast, relocated to the nucleus with ARVCF, and, given the interaction between the ZO-2 PDZ domains and ARVCF, raised the possibility that ZO-2 may play a role in nuclear localization of ARVCF. Such a role for ZO-2 is indeed supported by the ability of the ZO-2 PDZ domain to efficiently relocate ARVCF from the plasma membrane to the nucleus in a process that required the ability of the two proteins to interact and the presence of a functional NLS in the ZO-2 PDZ domains. Thus, ZO-2 could be involved in nuclear translocation and/or retention of ARVCF and play a role in regulating postulated functions of ARVCF in gene expression

SIGNOR-252122

Q9Y463

P28482

0

phosphorylation

up-regulates activity

0.369

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

SIGNOR-276937

P53778

Q13884

0

binding

down-regulates

0.368

Basal localization of the p38g/p-Carm1 complex in muscle stem cells occurs via binding to the dystrophin-glycoprotein complex (DGC) through b1-syntrophin. In dystrophin-deficient muscle stem cells undergoing asymmetric division, p38g/b1-syntrophin interactions are abrogated, resulting in enhanced Carm1 phosphorylation

SIGNOR-255901

P31946

Q05513

0

phosphorylation

down-regulates activity

0.368

Our results with the 14-3-3 mutants indirectly imply a new phosphorylation site, 130Ser (and to a lesser extent 141Thr), in 14-3-3b that regulates the association}dissociation of 14-3-3b and PKC-f.

SIGNOR-249035

P12036

P28482

0

phosphorylation

up-regulates activity

0.368

The fraction containing Erk2, as well as bacterially expressed Erk1 and Erk2, phosphorylated all types of KSP motifs in peptides (KSPXK, KSPXXK, KSPXXXK, and KSPXXXXK) derived from NF-M and NF-H. They also phosphorylated an expressed 24 KSPXXXK repeat NF-H polypeptide, an expressed NF-H as well as dephosphorylated native rat NF-H, and NF-M proteins with accompanying decreases in their respective electrophoretic mobilities. |Our data on primary hippocampal cells also showed an inhibition of neurite outgrowth by the drug that was accompanied by inhibition of MAP, NF-H, and NF-M phosphorylation.

SIGNOR-249424

O00418

P06493

0

phosphorylation

down-regulates

0.368

Phosphorylation at ser359 inhibits eef2k activity even at high calcium concentrations. we demonstrate that cdc2 contributes to controlling eef2 phosphorylation in cells. inactivation of eef2k by cdc2 may serve to keep eef2 active during mitosis

SIGNOR-177982

Q96GG9

P46934

0

monoubiquitination

up-regulates quantity

0.368

Here we revealed a previously unknown mechanism that regulates hDCNL1. In cultured mammalian cells ectopically expressed hDCNL1 was mono-ubiquitinated predominantly at K143, K149, and K171. Using a classical chromatographic purification strategy, we identified Nedd4-1 as an E3 ligase that can catalyze mono-ubiquitination of hDCNL1 in a reconstituted ubiquitination system.Taken together, these results suggest a mono-ubiquitination-mediated mechanism that governs nuclear-cytoplasmic trafficking of hDCNL1,

SIGNOR-272719

Q92900

Q13535

0

phosphorylation

up-regulates activity

0.368

Phosphorylation of UPF1 by the PIKKs SMG1, ATM and ATR is stimulated in response to DNA damage.

SIGNOR-278911

Q13144

P49840

0

phosphorylation

down-regulates activity

0.368

We identify multiple phosphorylation sites in the largest, catalytic, subunit (epsilon) of mammalian eIF2B. Glycogen synthase kinase 3 (GSK3) is responsible for phosphorylating Ser535. This regulatory phosphorylation event requires both the fourth site (Ser539) and a distal region, which acts to recruit GSK3 to eIF2Bepsilon in vivo. eIF2Bϵ from mammals or insects is a substrate for glycogen synthase kinase 3 (GSK3), and this inhibits the activity of eIF2B

SIGNOR-251215

O43524

Q13547

0

deacetylation

up-regulates activity

0.368

The ability of HDAC1 to cause muscle atrophy required its deacetylase activity and was linked to the induction of several atrophy genes by HDAC1, including atrogin-1, which required deacetylation of FoxO3a

SIGNOR-256486

Q13043

Q7L7X3

0

phosphorylation

up-regulates

0.368

In addition, the thousand-and-one (tao) amino acids kinase or taok13 has been shown to directly phosphorylate and activate hpo or mst1/2.

SIGNOR-201324

Q6STE5

Q16539

0

phosphorylation

up-regulates activity

0.368

P38 phosphorylates the baf60 subunit of the swi-snf chromatin remodelling complex, and p38 recruits this complex to differentiation-specific loci.

SIGNOR-176557

Q9H211

P45983

0

phosphorylation

up-regulates quantity by stabilization

0.368

We discovered that human Cdt1, an essential origin licensing protein whose activity must be restricted to G(1) phase, is a substrate of the stress-activated mitogen-activated protein (MAP) kinases p38 and c-Jun N-terminal kinase (JNK). These MAP kinases phosphorylate Cdt1 both during unperturbed G(2) phase and during an acute stress response. Phosphorylation renders Cdt1 resistant to ubiquitin-mediated degradation during S phase and after DNA damage by blocking Cdt1 binding to the Cul4 adaptor, Cdt2.

SIGNOR-276361

P08922

P29350

0

dephosphorylation

down-regulates

0.368

Overexpression of shp-1 results in ros dephosphorylation and effectively downregulates ros-dependent proliferation and transformation. We propose that shp-1 is an important downstream regulator of ros signaling.

SIGNOR-105922

P17612

O00408

0

binding

down-regulates activity

0.368

We show that caffeine, by inhibiting PDE2, enhances PKA phosphorylation leading to mitochondrial NCLX activation, thereby reducing neuronal excitotoxicity and enhancing learning in mice.

SIGNOR-275730

O14965

O94889

0

binding

up-regulates activity

0.368

We identify Aurora-A as a KLHL18-interacting partner. Overexpression of KLHL18 and CUL3 promotes Aurora-A ubiquitylation in vivo, and the CUL3-KLHL18-ROC1 ligase ubiquitylates Aurora-A in vitro. Our study reveals that the CUL3-KLHL18 ligase is required for timely entry into mitosis, as well as for the activation of Aurora-A at centrosomes.We also noticed that overexpression of both CUL3 and KLHL18 stimulated mono-ubiquitylation of Aurora-A as well (Fig. 8A,B).

SIGNOR-272021

P45973

P68400

0

phosphorylation

up-regulates

0.368

Hp1_ was multiply phosphorylated at n-terminal serine residues (s11-14) in human and mouse cells and that this phosphorylation enhanced hp1_'s affinity for h3k9me. Unphosphorylatable mutant hp1_ exhibited severe heterochromatin localization defects in vivo, and its prolonged expression led to increased chromosomal instability.

SIGNOR-171707

Q9Y6Q9

P06493

0

phosphorylation

down-regulates

0.368

We demonstrate that aib1 is phosphorylated on ser728 and ser867 by cdk1/cyclin b at the onset of mitosis and remains phosphorylated until exit from m phase.

SIGNOR-195233

P60880

Q9ULU8

0

binding

up-regulates activity

0.368

CAPS interacted independently with either syntaxin-1 or SNAP-25 suggesting that CAPS might promote QaQbc-SNARE heterodimer formation. CAPS binding to syntaxin-1 was mediated by the membrane-proximal C-terminal SNARE motif (H3) and membrane linker domain sequences of syntaxin-1

SIGNOR-264338

P48736

P10747

0

binding

up-regulates

0.368

Cd28 can bind directly to pi3k by a well-characterized ymnm binding motif in its cytoplasmic domain.

SIGNOR-159322

P07101

P17612

0

phosphorylation

up-regulates activity

0.368

HTH1 was phosphorylated at Ser40 by PKA. Tyrosine hydroxylase (TH) has been reported to require binding of 14-3-3 proteins for optimal activation by phosphorylation. phosphorylationof hTH1‚4 at Ser40, to a stoichiometry of up to 1.0 molphosphate per mol TH subunit, dramatically increases their binding to 14-3-3 proteins.

SIGNOR-250061

P62633

Q99873

0

methylation

down-regulates

0.368

Cnbp interacts with protein arginine methyltransferase prmt1 / r25 or r27 appear to be the major methylation sites in cnbp /arginine methylation of cnbp impedes rna binding

SIGNOR-204958

O15525

P27361

0

phosphorylation

up-regulates quantity

0.368

By contrast, MAFG-S124A was not phosphorylated, indicating that ERK1 phosphorylates MAFG at S124.|Notably, cotransfection of ERK1 increased total levels of wild-type MAFG and MAFG-T3A but not MAFG-S124A, indicating that phosphorylation increased MAFG stability.

SIGNOR-280027

P12931

Q8WTV0

0

binding

up-regulates activity

0.368

Importantly, coimmunoprecipitation of SR-BI and Src demonstrated that the two proteins are directly associated in WT macrophages (Fig. 7B), suggesting that SR-BI plays a direct role in activation of Src in macrophages.

SIGNOR-260314

P11274

P07332

0

phosphorylation

down-regulates activity

0.368

In the present study, we demonstrate that BCR Tyr-246 and at least one of the closely spaced tyrosine residues, Tyr-279, Tyr-283, and Tyr-289 (3Y cluster), are phosphorylated by FES both in vitro and in 32Pi-labeled cells. Co-expression of BCR and FES in human 293T cells stimulated the tyrosine autophosphorylation of FES. By contrast, tyrosine phosphorylation of BCR by FES suppressed BCR serine/threonine kinase activity toward the 14-3-3 protein and BCR substrate, BAP-1.

SIGNOR-251137

Q96FE7

P39880

0

transcriptional regulation

down-regulates quantity by repression

0.368

We demonstrate that CUX1 deficiency activates phosphoinositide 3-kinase (PI3K) signaling through direct transcriptional downregulation of the PI3K inhibitor PIK3IP1 (phosphoinositide-3-kinase interacting protein 1), leading to increased tumor growth and susceptibility to PI3K-AKT inhibition.

SIGNOR-260072

P49768

Q14790

0

cleavage

up-regulates activity

0.368

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

SIGNOR-261760

Q9UI46

Q92949

0

transcriptional regulation

up-regulates quantity by expression

0.368

FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).

SIGNOR-266932

P25490

Q96GD4

0

phosphorylation

up-regulates

0.368

Aurora b kinase phosphorylates yy1 on serine 184 and to a lesser extent serine 180 at the g2/m stage of the cell cycle (fig. 7). We show that yy1 is rapidly dephosphorylated as the cells exit mitosis, likely by pp1. Also, our data indicates that phosphorylation at serine 180 and serine 184 can affect the dna binding activity of yy1

SIGNOR-200079

P00533

Q05655

0

phosphorylation

down-regulates activity

0.368

These data indicate that activation of protein kinase C and subsequent phosphorylation of the EGF receptor at T654 lead to rapid physiological attenuation of EGF receptor signaling.

SIGNOR-248858

Q13887

P49841

0

phosphorylation

down-regulates

0.368

Stability of the klf5 is mediated by proteasomal degradation via phosphorylation by glycogen synthase kinase 3_ (gsk3_) and recognition by f-box and wd repeat domain-containing 7 (fbw7) of a phosphodegron sequence surrounding serine 303 in klf5

SIGNOR-203627

P11831

O43474

0

binding

down-regulates

0.368

Klf4 antagonizes contractile gene expression through diverse mechanisms including (i) inhibiting the binding of srf-myocd or srf-mrtfs to the carg box by direct association with srf.

SIGNOR-174258

P25963

P51812

0

phosphorylation

down-regulates quantity by destabilization

0.368

Here, we show that RSK2 is activated by treatment with tumor necrosis factor-alpha (TNF-alpha) and directly phosphorylates IkappaBalpha at Ser 32, leading to IkappaBalpha degradation.

SIGNOR-279108

P15498

P12931

0

phosphorylation

up-regulates activity

0.368

These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module.|These interactions are required for SRC-induced tyrosine phosphorylation and activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module ( xref ).

SIGNOR-279124

Q05469

P28482

0

phosphorylation

up-regulates activity

0.368

Thus, activation of the ERK pathway appears to be able to regulate adipocyte lipolysis by phosphorylating HSL on Ser(600) and increasing the activity of HSL.

SIGNOR-249413

O14939

Q00535

0

phosphorylation

up-regulates activity

0.368

In this study, we suggest that the phosphorylation and activation of PLD2 by cyclin-dependent kinase 5 (Cdk5) is critical for EGF-dependent insulin secretion.|We determined that Cdk5 phosphorylates PLD2 at Ser 134 of PLD2 and that this phosphorylation was suggested to be important for EGF-dependent insulin secretion.

SIGNOR-278395

P12830

P06493

0

phosphorylation

up-regulates activity

0.368

We show that adequate accumulation of Cin8 and Kip1 requires inactivation of the anaphase promoting complex-activator Cdh1 through sequential phosphorylation by Cdk1 and polo kinase.|We show that adequate accumulation of Cin8 and Kip1 requires inactivation of the anaphase-promoting complex-activator Cdh1 through sequential phosphorylation by Cdk1 and polo kinase.

SIGNOR-280204

P23396

P31749

0

phosphorylation

up-regulates activity

0.368

Here, we show that human RPS3 is a physiological target of Akt kinase and a novel mediator of neuronal apoptosis. NGF stimulation resulted in phosphorylation of threonine 70 of RPS3 by Akt, and this phosphorylation was required for Akt binding to RPS3.our experiment demonstrated that Akt up-regulates the endonuclease activity of RPS3 via phosphorylation and led us to believe that Akt phosphorylation of RPS3 after DNA damage is an antiapoptotic signal or a molecular switch that extends the life of a cell after DNA damage.

SIGNOR-259815

P07949

Q9ULV8

0

ubiquitination

down-regulates quantity by destabilization

0.368

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

SIGNOR-278674

Q6P1J9

Q13882

0

phosphorylation

down-regulates activity

0.368

PTK6 impairs the coactivator function of parafibromin.|To study the functional consequence of parafibromin phosphorylation by PTK6, we examined the effect of PTK6 inhibition on Wnt signal activation.

SIGNOR-279273

Q13332

Q96NI6

0

binding

up-regulates activity

0.368

SALM5 trans-synaptically interacts with LAR-RPTPs in a splicing-dependent manner to regulate synapse development. we identified LAR-RPTPs as novel ligands of SALM5 that mediates SALM5-dependent presynaptic differentiation in a splicing-dependent manner. Our data indicate that SALM5 interacts with all three known LAR-RPTPs—LAR, PTPδ, and PTPσ (Fig. 1).

SIGNOR-264088

P46527

Q8TAS1

0

phosphorylation

up-regulates

0.367

Hkis is a nuclear protein that binds the c-terminal domain of p27(kip1) and phosphorylates it on s10 in vitro and in vivo, promoting its nuclear export to the cytoplasm.Phosphorylation at serine 10, a major phosphorylation site of p27(kip1), increases its protein stability

SIGNOR-90274

Q99683

Q06124

0

dephosphorylation

up-regulates

0.367

Previously we have shown that tyrosine 718 of ask1 when phosphorylated is critical for socs1 binding and socs1-mediated degradation of ask1we identified jak2 and shp2 as a tyr-718-specific kinase and phosphatase, respectively.

SIGNOR-184604

Q13813

O15287

0

null

up-regulates quantity by stabilization

0.367

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

SIGNOR-263275

Q15700

P06241

0

phosphorylation

up-regulates activity

0.367

Recombinant PSD-93 was phosphorylated by Fyn in vitro, and Tyr-384 was identified as a major phosphorylation site. In COS7 cells, exogenously expressed PSD-93 was phosphorylated, dependent on its membrane localization. In addition, tyrosine-phosphorylated PSD-93 was able to bind to Csk, a negative regulator of Src family kinases, in vitro as well as in a brain lysate.

SIGNOR-262874

Q9NZV8

P28482

0

phosphorylation

up-regulates activity

0.367

We determined that the Kv4.2 C-terminal cytoplasmic domain is an effective ERK2 substrate, and that it is phosphorylated at three sites: Thr(602), Thr(607), and Ser(616). Phosphorylation of the Kv4.2 channel by ERK during LTP induction may lead to increased excitability and membrane depolarization of neurons, which would increase the magnitude of the calcium influx and the probability of triggering LTP.

SIGNOR-262935

P63000

Q8IYU2

0

ubiquitination

down-regulates quantity by destabilization

0.367

The CNF1 toxin of pathogenic Escherichia coli addresses Rac1 to ubiquitin-proteasome system (UPS). We report the essential role of the tumor suppressor HACE1, a HECT-domain containing E3 ubiquitin-ligase, in the targeting of Rac1 to UPS. HACE1 binds preferentially GTP-bound Rac1 and catalyzes its polyubiquitylation

SIGNOR-255538

Q9UK53

P12931

0

phosphorylation

down-regulates activity

0.367

Src Decreases the Stability and Level of ING1.|This study, as well as a previous report identifying Ser-126 of ING1 as a kinase target, confirm that ING1 stability is also regulated by phosphorylation. However, the mechanism may be complex since phosphorylation of Ser-126 stabilizes the protein while phosphorylation by Src reduces ING1 stability and causes a relocalization of ING1 from the nucleus to the cytoplasm.

SIGNOR-279760

P46459

Q5S007

0

phosphorylation

up-regulates activity

0.367

LRRK2 phosphorylates full-length NSF at threonine 645 in the ATP binding pocket of D2 domain. Functionally, NSF phosphorylated by LRRK2 displays enhanced ATPase activity and increased rate of SNARE complex disassembling.

SIGNOR-277196

P40763

Q14526

0

binding

down-regulates quantity by repression

0.367

HIC1 interacts with the DNA binding domain of STAT3 and suppresses the binding of STAT3 to its target gene promoters. HIC1 C-terminal domain binds to STAT3. HIC1 mutant defective in STAT3 interaction reduced its repressive effect on STAT3 DNA binding activity, the reporter activity and gene expression of the VEGF and c-Myc genes, and cell growth in MDA-MB 231 cells.

SIGNOR-254246

Q12906

P31749

0

phosphorylation

up-regulates activity

0.367

Upon T cell activation, NF90 translocates from the nucleus into the cytoplasm, where it binds to the AU-rich element-containing 3' untranslated regions of IL-2 mRNA and stabilizes it.|Our previous work showed that CD28 costimulation of T cells activated AKT to phosphorylate NF90 at Ser647 and caused NF90 to undergo nuclear export and stabilize IL-2 mRNA.

SIGNOR-252512

Q01094

Q92466

0

binding

up-regulates

0.367

We show that ddb, a putative dna repair protein, associates with the activation domain of e2f1 / expression of ddb specifically stimulated e2f1-activated transcription

SIGNOR-54102

Q9Y6R4

P49841

0

binding

down-regulates

0.367

Gsk3beta binding to mekk4 blocks mekk4 dimerization that is required for mekk4 activation, effectively inhibiting mekk4 stimulation of the jnk and p38 mapk pathways

SIGNOR-157541

P22736

Q15349

0

phosphorylation

down-regulates activity

0.367

Phosphorylation of a residue in the DNA-binding region (Ser-350 of NGFI-B and 354 of Nur77) has been described in detail to have effect on the transcriptional function of the protein [11, 24]. Growth-related kinase pp90rsk, but not ERK1 (pp44mapk), was shown to phosphorylate recombinant Nur77 in vitro in the DNA binding domain, but not the amino-terminus, using an immune complex kinase as- say [11].

SIGNOR-249429

Q13501

Q05655

0

phosphorylation

up-regulates activity

0.367

Data presented here suggested that Vps34 stimulates tumor development mainly through PKC-\u03b4- activation of p62.|In conclusion, elevation of Vps34 results in tumor progression via the PKC-\u03b4-phosphorylation of p62 at S349 and PKC-\u03b4 involved phosphorylation of Raf 1 at Y340/341.|Vps34 induces PKC-\u03b4-dependent phosphorylation of p62.

SIGNOR-280086

P15173

Q96NX9

0

transcriptional regulation

down-regulates quantity by repression

0.367

We confirmed Dach2 is a Mgn transcriptional repressor that mediates HDAC-dependent regulation by (i) overexpressing Dach2 in myotubes harboring the 133-bp Mgn promoter and (ii) rescuing TSA-mediated Mgn repression by Dach2 knockdown.

SIGNOR-261579

P23443

Q9HC98

0

phosphorylation

up-regulates activity

0.367

Here we demonstrate that in addition to phosphorylating S6K1 and SGK1 at their hydrophobic motif, NEK6 also phosphorylates S6K1 at two other sites and phosphorylates SGK1 at one other site in vitro. Analysis of the peptides phosphorylated by NEK6 (Fig 2), performed in the present study has confirmed this, and identified two novel sites on S6K1 (Ser53 and Ser403) as major sites of NEK6 phosphorylation.

SIGNOR-262953

Q92993

P49841

0

phosphorylation

up-regulates

0.367

We demonstrate that gsk-3 phosphorylates serine 86 of the p53-acetyltransferase tip60. A tip60(s86a) mutant was less active to induce p53 k120 acetylation, histone 4 acetylation, and expression of puma

SIGNOR-174049

P41235

P54646

0

phosphorylation

down-regulates quantity by destabilization

0.367

AMPK directly phosphorylates HNF4alpha and represses its transcriptional activity. AMPK-mediated phosphorylation of HNF4alpha on serine 304 had a 2-fold effect, reducing the ability of the transcription factor to form homodimers and bind DNA and increasing its degradation rate in vivo. Phosphorylation of HNF4α on Ser-304 reduces protein stability.

SIGNOR-250322

Q99683

O60674

0

phosphorylation

down-regulates quantity by destabilization

0.367

Furthermore, JAK2, but not JAK1, directly bound to and phosphorylated ASK1 at Tyr-718, leading to an enhanced association of ASK1 with SOCS1 and subsequent ASK1 degradation.

SIGNOR-276145

Q13043

P67775

0

dephosphorylation

down-regulates

0.367

Rassf1a apparently protects mst1/2 against inactivation by pp2a , the phosphatases that dephosphorylate the stimulatory thr-183 and thr-180 of mst1 andmst2, respectively.

SIGNOR-201270

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

O75444

P35452

0

binding

down-regulates activity

0.367

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-221887

P46531

Q13233

0

phosphorylation

down-regulates activity

0.367

As a result, MEKK1 suppresses the Notch1 intracellular domain protein stability and transcriptional activity.|We confirmed that MEKK1 binds to Notch1 intracellular domain and phosphorylates the Notch1 intracellular domain Threonine 2512 residue.

SIGNOR-279628

Q70Z35

Q13153

0

phosphorylation

down-regulates activity

0.367

P21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase. PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ.

SIGNOR-277181

Q16204

Q969H0

0

binding

down-regulates

0.367

Fbxw7 interacts with and targets ccdc6 for ubiquitin-mediated proteasomal degradation

SIGNOR-199279

Q8IZL8

P24941

0

phosphorylation

up-regulates

0.367

We identified ser(477) and ser(991) of pelp1 as cdk phosphorylation sites. we conclude that pelp1 is a novel substrate of interphase cdks and that its phosphorylation is important for the proper function of pelp1 in modulating hormone-driven cell cycle progression and also for optimal e2f transactivation function.

SIGNOR-167766

Q9NRH2

Q15831

0

phosphorylation

up-regulates activity

0.367

We demonstrate that LKB1 activates SNRK by phosphorylating the T‐loop residue (Thr173)

SIGNOR-260824

Q9BXM7

Q7KZI7

0

phosphorylation

up-regulates activity

0.367

MARK2 phosphorylated and activated the cleaved form of PINK1 (DeltaN-PINK1

SIGNOR-278975

Q13950

Q16539

0

phosphorylation

up-regulates activity

0.367

Mechanistic analysis revealed that the TAK1–MKK3/6–p38 MAPK axis phosphorylated Runx2, promoting its association with the coactivator CREB-binding protein (CBP), which was required to regulate osteoblast genetic programs. These findings reveal an in vivo function for p38β and establish that MAPK signaling is essential for bone formation in vivo.

SIGNOR-255777

P08670

Q13464

0

phosphorylation

down-regulates activity

0.367

We found that vimentin, the most widely expressed intermediate filament protein, served as an excellent substrate for Rho-associated kinase (Rho-kinase) and that vimentin phosphorylated by Rho-kinase lost its ability to form filaments in vitro. Two amino-terminal sites on vimentin, Ser38 and Ser71, were identified as the major phosphorylation sites for Rho-kinase, and Ser71 was the most favored and unique phosphorylation site for Rho-kinase in vitro.

SIGNOR-248998

Q53EZ4

P28482

0

phosphorylation

down-regulates

0.367

Upon mitotic entry, centrosome dissociation of cep55 is triggered by erk2/cdk1-dependent phosphorylation at s425 and s428. S425/428 phosphorylation is required for interaction with plk1, enabling phosphorylation of cep55 at s436. enabling it to relocate to the midbody to function in mitotic exit and cytokinesis.

SIGNOR-140890

P11532

Q12955

0

relocalization

up-regulates quantity

0.367

We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4.

SIGNOR-266715

Q16204

P27361

0

phosphorylation

up-regulates activity

0.367

We have characterized the H4(D10S170) gene product, showing that it is a ubiquitously expressed 55 KDa nuclear and cytosolic protein that is phosphorylated following serum stimulation. This phosphorylation was found to depend on mitogen-activated protein kinase (MAPK) Erk1/2 activity and to be associated to the relocation of H4(D10S170) from the nucleus to the cytosol. S244 is the major target residue of ERK1

SIGNOR-276003

P12259

P08246

0

cleavage

up-regulates activity

0.366

Human neutrophil elastase activates human factor V but inactivates thrombin-activated human factor V|NH2-terminal sequence analysis of F.V treated with HNE indicated cleavage at Ile819 and Ile1484 under conditions during which the procofactor expressed enhanced cofactor activity in the prothrombinase complex.

SIGNOR-263637

P30304

Q15418

0

phosphorylation

down-regulates

0.366

Rsk promotes g2/m transition through activating phosphorylation of cdc25a and cdc25b rsk is likely to be more active in mitotic cells than in interphase cells, as evidenced by the phosphorylation status of t359/s363 in rsk. Together, these findings indicate that rsk promotes g2/m transition in mammalian cells through activating phosphorylation of cdc25a and cdc25b.

SIGNOR-202117

P14136

P17252

0

phosphorylation

down-regulates activity

0.366

Glial fibrillary acidic protein (GFAP), the intermediate filament component of astroglial cells, can serve as an excellent substrate for both cAMP-dependent protein kinase and protein kinase C, in vitro. GFAP phosphorylated by each protein kinase does not polymerize, and the filaments that do polymerize tend to depolymerize after phosphorylation. Dephosphorylation of phospho-GFAP by phosphatase led to a recovery of the polymerization competence of GFAP. Most of the phosphorylation sites for cAMP-dependent protein kinase and protein kinase C on GFAP are the same, Ser-8, Ser-13, and Ser-34. cAMP-dependent protein kinase has one additional phosphorylation site, Thr-7.

SIGNOR-248862

Q96QF0

Q15208

0

phosphorylation

up-regulates activity

0.366

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

SIGNOR-263036

Q16760

P17252

0

phosphorylation

down-regulates activity

0.366

The plasma membrane translocation of diacylglycerol kinase delta1 is negatively regulated by conventional protein kinase C-dependent phosphorylation at Ser-22 and Ser-26 within the pleckstrin homology domain.

SIGNOR-249265

Q13285

P50613

0

phosphorylation

up-regulates

0.366

In conclusion, our results indicate that cdk7, as part of the cak complex and tfiih, phosphorylates sf1 at s203 followed by increased transcriptional activity of sf1

SIGNOR-157952

P00338

P11362

0

phosphorylation

up-regulates

0.366

We found that the oncogenic receptor tyrosine kinase fgfr1 directly phosphorylates ldh-a. Phosphorylation at y10 and y83 enhances ldh-a activity by enhancing the formation of active, tetrameric ldh-a and the binding of ldh-a substrate nadh, respectively.

SIGNOR-176730

P04637

Q9BV47

0

dephosphorylation

down-regulates activity

0.366

Dual-specificity phosphatase 26 is a novel p53 phosphatase and inhibits p53 tumor suppressor functions in human neuroblastoma|Inhibiting DUSP26 expression in the IMR-32 neuroblastoma cell line enhanced doxorubicin-induced p53 phosphorylation at Ser20 and Ser37, p21, Puma, Bax expression as well as apoptosis

SIGNOR-248765

O95816

P49137

0

phosphorylation

up-regulates

0.366

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

SIGNOR-126953

Q13233

P01116

0

binding

up-regulates

0.366

Mitogen-activated protein kinase kinase kinase (mekk1) is a serine-threonine kinase that regulates sequential protein kinase pathways involving stress-activated protein kinases and mitogen-activated protein kinases. Mekk1 is activated in response to growth factor stimulation of cells and by expression of activated ras. mekk1 directly binds ras.GTP. Thus, ras interacts with protein kinases of both the raf and mekk families.

SIGNOR-32620

P35712

Q00535

0

phosphorylation

down-regulates quantity

0.366

GST-Sox6 was phosphorylated in vitro by Cdk5 and p35 (XREF_FIG).|Inhibition of Cdk5 activity by DN Cdk5 and roscovitine increases the Sox6 expression in primary cortical neurons.

SIGNOR-279365

P61204

Q9Y6D6

0

guanine nucleotide exchange factor

up-regulates activity

0.366

Brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) is an approximately 200-kDa brefeldin A-inhibited guanine nucleotide-exchange protein that preferentially activates ADP-ribosylation factor 1 (ARF1) and ARF3.

SIGNOR-272148

Q13224

Q96AX9

0

ubiquitination

down-regulates quantity

0.366

Mib2 is localized to the PSD of dendrites in hippocampal neurons and directly ubiquitinates GluN2B in a manner dependent on the non receptor tyrosine kinase Fyn.|These findings suggest that Mib2 mediates proteasome dependent degradation of GluN2B subunits, which may provide a reciprocal mechanism to SCF Fbx2 regulation of GluN2A.

SIGNOR-278762

Q6UXI9

Q5H8C1

0

transcriptional regulation

up-regulates quantity by expression

0.366

The loss of QBRICK significantly diminished the expression of nephronectin, an integrin α8β1 ligand necessary for renal development. In vivo, nephronectin associated with QBRICK and localized at the sublamina densa region, where QBRICK was also located. Collectively, these findings indicate that QBRICK facilitates the integrin α8β1-dependent interactions of cells with basement membranes by regulating the basement membrane assembly of nephronectin and explain why renal defects occur in Fraser syndrome.

SIGNOR-253308

Q9GZV5

P48730

0

phosphorylation

down-regulates

0.366

LATS1/2-mediated phosphorylation of a conserved serine in this region (Ser311 in human TAZ; Ser397 in human YAP) primes for further phosphorylation by CK1_/_ kinases (Ser314 on human TAZ; Ser400/403 in human YAP)

SIGNOR-234438

Q16623

P68400

0

phosphorylation

up-regulates

0.366

In this report, we show that syntaxin-1a is phosphorylated in vitro by cki on thr21. Casein kinase ii (ckii) has been shown previously to phosphorylate syntaxin-1a in vitro and we have identified ser14 as the ckii phosphorylation site. the phosphorylation of syntaxin-1a by ckii enhances its capacity to associate with synaptotagmin [21]. Therefore, phosphorylation of ser14 by ckii suggests an important role for this residue in regulating the interaction between syntaxin-1a and synaptotagmin

SIGNOR-114840

A5D8V6

Q9UHD2

0

phosphorylation

down-regulates activity

0.366

We have identified that TBK1 may target and phosphorylate VPS37C, a structural component of ESCRT-I complex, and serve as a ratelimiting factor in the control of PTAP-dependent (HIV-1, MLV/p6, and EIAV/PTAP), but not PPPY-dependent (MLV, EIAV/PPPY) retrovirus budding, independent of its role in IFN-I signaling.

SIGNOR-279768

Q13158

Q9BV47

0

dephosphorylation

down-regulates activity

0.366

This multi-functionality of fadd may depend primarily on its subcellular location. Fadd shuttles between the cytosol and the nucleus and this signal is unclear;however, fadd trafficking requires phosphorylation of the protein on ser194dusp26 suppresses cell proliferation by fadd dephosphorylation

SIGNOR-204559

Q09472

Q05655

0

phosphorylation

down-regulates

0.366

Inhibition of histone acetyltransferase function of p300 by pkcdeltawe found that pkcdelta but not classical pkc, specifically phosphorylates p300 at serine 89 in vitro and in vivo. This phosphorylation causes inhibition of p300 intrinsic hat activity.

SIGNOR-94263

P54274

Q96GD4

0

phosphorylation

up-regulates activity

0.366

Our data indicate that AURKB can phosphorylate the integral telomere DNA-binding Shelterin protein TERF1 at S404 (within the DNA-binding domain) in vitro .

SIGNOR-279440

Q9Y6X9

Q13153

0

phosphorylation

up-regulates activity

0.366

We demonstrate that PAK1-mediated MORC2 phosphorylation promotes cell cycle progression, defective phosphorylation of MORC2-S677A results in attenuated cell proliferation and tumorigenicity of gastric cancer cells, which is significantly enhanced in overexpression of phospho-mimic MORC2-S677E form, suggesting the importance of MORC2 phosphorylation in tumorigenesis.

SIGNOR-273714

Q8N726

Q9UHC7

0

polyubiquitination

down-regulates quantity by destabilization

0.366

Biochemical analyses confirmed that MKRN1 targets p14ARF for ubiquitination and subsequent proteasome-dependent degradation.The Skp1-Cul1-F-box-protein44 (SCF(FBXO44)) complex ubiquitinates full-length BRCA1 in vitro.

SIGNOR-272036

Q96J02

P06241

0

phosphorylation

down-regulates activity

0.366

Tyrosine phosphorylation of Itch appears to reduce its interaction with its substrate JunB. The turnover of JunB is accelerated in Fyn-deficient T cells, which is further reconstituted by Itch Tyr371 mutation

SIGNOR-245332

Q12913

P06241

0

phosphorylation

up-regulates activity

0.366

We demonstrate here that DEP-1 is phosphorylated in a Src- and Fyn-dependent manner on Y1311 and Y1320, which bind the Src SH2 domain. This allows DEP-1-catalyzed dephosphorylation of Src inhibitory Y529 and favors the VEGF-induced phosphorylation of Src substrates VE-cadherin and Cortactin.

SIGNOR-276372

Q9UDY8

Q5T447

0

polyubiquitination

up-regulates quantity by stabilization

0.366

HECTD3 promotes MALT1 ubiquitination with nondegradative polyubiquitin chains by direct interacting with the MALT1 through its N-terminal destruction of cyclin domain. HECTD3 does not target MALT1 for degradation but stabilize it.

SIGNOR-272096