GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P01137	P01137	2	binding	up-regulates activity	0.2	The active form of TGF-beta is a dimer stabilized by hydrophobic interactions and usually further strengthened by an intersubunit disulfide bridge.	SIGNOR-148605
P46020	P46020	2	phosphorylation	up-regulates activity	0.2	Phk is activated in vitro by autophosphorylation. Ser1018 and at least three of the other six serine residues (Ser972, -985, and -1007) can be phosphorylated in vitro by Phk itself (autophosphorylation)	SIGNOR-250282
Q13627	Q13627	2	phosphorylation	up-regulates	0.2	Mirk kinase is activated by autophosphorylation on tyrosine at the y271/y273 site	SIGNOR-79760
P43405	P43405	2	phosphorylation	up-regulates activity	0.2	These represented sites of tyrosine phosphorylation previously identified from the study of in vitro autophosphorylated Syk. Phosphorylation was observed on peptides corresponding to Tyr130, Tyr317, Tyr342, Tyr346, Tyr519, and Tyr520	SIGNOR-246621
Q15831	Q15831	2	phosphorylation	up-regulates activity	0.2	It was shown that thr336 and thr366 are the major autophosphorylation sites of mouse lkb1 (sapkota et al., 2002). We confirmed these data on the human orthologues thr336 and thr363. Moreover, the enhanced stoichiometry of lkb1 autophosphorylation by strad enabled us to identify two novel sites: thr185 and thr402. We show that increased lkb1 autophosphorylation of all sites correlates with the activation of its catalytic activity.	SIGNOR-101844
Q9NYL2	Q9NYL2	2	phosphorylation	up-regulates	0.2	Ionizing radiation induces mrk autophosphorylation and activation. Within the mrk kinase loop between the dfg (subdomain vii) and ape (subdomain viii) residues, there are three conserved threonine/serine residues (thr161, thr162, and ser165) that are important for activation.	SIGNOR-128581
P29466	Q96EP0	2	polyubiquitination	up-regulates activity	0.2	HOIP forms a constitutive interaction with caspase-1 and mediates the linear ubiquitination of the CARD pro-domain. Upon engagement of apoptosis, caspase-1 and caspase-8 cleave HOIP at Asp-348 and Asp-387, limiting the ability of LUBAC to ubiquitinate substrates.	SIGNOR-272191
P15056	P15056	2	phosphorylation	down-regulates activity	0.2	We previously identified that BRAFWT can autophosphorylate its P-loop (Ser-465/Ser-467) to inactivate itself in the absence of native substrate MEK	SIGNOR-277498
O96017	O96017	2	phosphorylation	up-regulates activity	0.2	Thus, activation of chk2 in irradiated cells may occur through oligomerization of chk2 via binding of the thr-68-phosphorylated region of one chk2 to the fha domain of another. Oligomerization of chk2 may therefore increase the efficiency of trans-autophosphorylation resulting in the release of active chk2 monomers that proceed to enforce checkpoint control in irradiated cells.	SIGNOR-116135
Q05513	Q05513	2	phosphorylation	up-regulates	0.2	Our findings suggest that insulin, via pip(3), provokes increases in pkc-zeta enzyme activity through (a) pdk-1-dependent t410 loop phosphorylation, (b) t560 autophosphorylation	SIGNOR-85505
Q96SB4	Q96SB4	2	phosphorylation	up-regulates	0.2	We found that activated akt binds and induces srpk1 autophosphorylation because akt-mediated phosphorylation depends on the kinase activity of srpk1	SIGNOR-197989
O43353	O43353	2	phosphorylation	up-regulates activity	0.2	In summary, our results indicate that s176 is a regulatory autophosphorylation site for rip2 and that s176 phosphorylation can be used to monitor the activation state of rip2.	SIGNOR-229701
P30530	P30530	2	phosphorylation	up-regulates activity	0.2	Our data showed that various receptor substrates are at least associated with the C-terminal tyrosine pY821. Two additional potential autophosphorylation sites (pY866 and pY779) may play a minor role in binding of eector proteins	SIGNOR-250593
Q16611	Q16611	2	binding	up-regulates	0.2	Allosteric activation of bak induces its intramembranous oligomerization into a proposed pore for cytochrome c efflux	SIGNOR-105203
P35269	P35269	2	phosphorylation	down-regulates	0.2	We show that tfiifalpha possesses a serine/threonine kinase activity, allowing an autophosphorylation of the two residues at position serine 385 and threonine 389. Mutation analysis strongly suggests that autophosphorylation of both sites regulates the transcription elongation process.	SIGNOR-69767
P37173	P37173	2	phosphorylation	down-regulates activity	0.2	Ser213, in the membrane-proximal segment outside the kinase domain, undergoes intra-molecular autophosphorylation which is essential for the activation of TbetaRII kinase activity, activation of TbetaRI and TGF-beta-induced growth inhibition. In contrast, phosphorylation of Ser409 and Ser416, located in a segment corresponding to the substrate recognition T-loop region in a three-dimensional structural model of protein kinases, is enhanced by receptor dimerization and can occur via an intermolecular mechanism. Phosphorylation of Ser409 is essential for TbetaRII kinase signaling, while phosphorylation of Ser416 inhibits receptor function.	SIGNOR-246737
Q15759	Q15759	2	phosphorylation	up-regulates activity	0.2	P38β Mitogen-Activated Protein Kinase Modulates Its Own Basal Activity by Autophosphorylation of the Activating Residue Thr180 and the Inhibitory Residues Thr241 and Ser261	SIGNOR-277216
Q13882	Q13882	2	phosphorylation	up-regulates	0.2	Autophosphorylation increases enzyme activity of wild-type brk but not of a y342a mutant form of brk.	SIGNOR-90604
Q15418	Q15418	2	phosphorylation	up-regulates activity	0.2	Herein, we demonstrate that the n-terminal kinase domain (ntk) of rsk1 is necessary for interactions with pkarialpha. Substitution of the activation loop phosphorylation site (ser-221) in the ntk with the negatively charged asp residue abrogated the association between rsk1 and pkarialpha.	SIGNOR-162681
Q13239	P10721	2	phosphorylation	down-regulates activity	0.2	Oncogenic c-Kit-D816V phosphorylates SLAP on residues Y120, Y258 and Y273. Mutation of the SLAP tyrosine phosphorylation sites rescues its activity	SIGNOR-263141
O60674	O60674	2	phosphorylation	up-regulates	0.2	Autophosphorylation of jak2 on tyrosines 221 and 570 regulates its activity with phosphorylation of tyrosine 221 increasing kinase activity	SIGNOR-236506
Q13546	Q13546	2	phosphorylation	up-regulates activity	0.2	These data suggest that Ser14/15, Ser20, Ser161 and Ser166 represent autophosphorylation sites in vitro, detected in the RIP1 kinase assay (Fig. 1)	SIGNOR-276159
Q8TD19	Q8TD19	2	phosphorylation	up-regulates	0.2	We find that the interaction of lc8 with nek9 depends on a (k/r)xtqt motif adjacent to the nek9 c-terminal coiled coil motif, results in nek9 multimerization, and increases the rate of nek9 autoactivation. Lc8 binding to nek9 is regulated by nek9 activity through the autophosphorylation of ser(944), a residue immediately n-terminal to the (k/r)xtqt motif.	SIGNOR-173026
P54764	P54764	2	phosphorylation	up-regulates activity	0.2	Two dimensional phosphopeptide mapping and site-directed mutagenesis defined juxtamembrane residue Y602 as a major site of in vitro autophosphorylation in Sek, whilst Y596 was phosphorylated to a lower stoichiometry.	SIGNOR-251118
Q9H4A3	Q9H4A3	2	phosphorylation	up-regulates	0.2	We demonstrate that wnk1 is rapidly activated and phosphorylated at multiple residues after exposure of cells to hyperosmotic conditions and that activation is mediated by the phosphorylation of its t-loop ser382 residue, possibly triggered by a transautophosphorylation reaction.	SIGNOR-160850
Q9H9S0	Q9H9S0	2	transcriptional regulation	up-regulates quantity by expression	0.2	We conclude that the Nanog enhancer activity is regulated by both Sall4 and Nanog.	SIGNOR-266080
O14757	O14757	2	phosphorylation	up-regulates activity	0.2	This suggests that Ser296 is probably one of the sites autophosphorylated when Chk1 is fully activated [21], despite the sequence surrounding Ser296 (FSKHIQS296NL) being only weakly related to the optimal Chk1-recognition motif (M/I/L/V)-X-(R/K)-X-X-(S/T), where (S/T) is the phosphorylated residue	SIGNOR-219240
P22607	P22607	2	phosphorylation	up-regulates activity	0.2	Ligand stimulation leads to autophosphorylation of fgfr3 the absence of y577 (3y-577f) or y760 (3y-760f) resulted in a modest decrease in activity.	SIGNOR-106726
P00533	P00533	2	phosphorylation	up-regulates activity	0.2	EGFR possesses three major and two minor tyrosine autophosphorylation sites located at Y1068, Y1148, Y1173, and at Y992 and Y1086 respectively. In addition, EGFR Y1114 is preceded by glutamic acid (Figure 1), which should be preferred by the EGFR kinase as indicated in previous work	SIGNOR-236527
P36888	P36888	2	phosphorylation	up-regulates	0.2	Previously we reported that flt3 with itd (flt3/itd) formed a homodimer and was autophosphorylated on tyrosine residuewe examined the role of tyr residues (y589, y591, y597 and y599) in the jm domain in the activation of flt3. In wt-flt3, these tyr residues were important for the fl-dependent activation	SIGNOR-117575
Q9Y653	Q9Y653	2	cleavage	up-regulates activity	0.2	Like many other adhesion GPCRs, GPR56 is cleaved via a GPCR autoproteolysis-inducing (GAIN) domain into N- and C-terminal fragments (GPR56N and GPR56C); \| We demonstrate that ligand binding releases GPR56N from the membrane-bound GPR56C and triggers the association of GPR56C with lipid rafts and RhoA activation.	SIGNOR-253980
Q16649	Q16649	2	binding	up-regulates activity	0.2	E4BP4, ATF-6, OASIS, and XBP-1 all formed strong homodimeric associations on the array Transcription factor dimerization can increase the selectivity of protein-DNA interactions and generate a large amount of DNA binding diversity from a relatively small number of proteins	SIGNOR-224248
P60484	P60484	2	dephosphorylation	up-regulates activity	0.2	Overall, our results suggest that PTEN autodephosphorylation may be a critical event in this process; thus a major protein substrate for PTEN may be PTEN itself.\|Various studies have demonstrated that PTEN is itself a phosphoprotein, and that the major sites of phosphorylation are found in an acidic stretch (DHYRYSDTTDSDPENE) near the C-terminus [1]. This prompted us to consider whether PTEN may autodephosphorylate these sites	SIGNOR-248545
P07947	P07947	2	phosphorylation	up-regulates activity	0.2	Autophosphorylation of Src and Yes blocks their inactivation by Csk phosphorylation	SIGNOR-247014
P08069	P08069	2	phosphorylation	up-regulates activity	0.2	Insulin and insulin-like growth factor (igf-i) receptors are heterotetrameric proteins consisting of two alpha-and two beta-subunits and members of the transmembrane tyrosine kinase receptors. Specific ligand binding to the receptor triggers a cascade of intracellular events, which begins with autophosphorylation of several tyrosine residues of the beta-subunit of the receptor.	SIGNOR-26582
P45985	P45985	2	phosphorylation	up-regulates activity	0.2	Ser221 and, to a lesser extent, Thr225 in MKK4 as necessary sites for basal and MEKK-induced autophosphorylation and activation of MKK4.	SIGNOR-251420
Q13188	Q13188	2	phosphorylation	up-regulates	0.2	Consistent with previous studies, sts alone induces mst2 cleavage and autophosphorylation of thr180, an indicator of mst2 activation, as well as apoptosis.	SIGNOR-164310
P13861	P13861	2	phosphorylation	up-regulates activity	0.2	RII subunit containing the 'autophosphorylation' site (Ser-95)	SIGNOR-250073
P01019-PRO_0000032457	Q9BYF1	2	cleavage	up-regulates activity	0.2	The ACE2 hydrolytic activity is dependent on the C terminus sequence of the substrate, which is evident from the data with the angiotensin peptides. After 2 h, ACE2 hydrolyzes Ang I partially and Ang II completely, although there is no hydrolysis of angiotensin 1â€“9, angiotensin 1â€“7, and angiotensin 1â€“5, which possess the same N terminus.	SIGNOR-260222
P27361	P27361	2	phosphorylation	up-regulates activity	0.2	Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation.\|	SIGNOR-249471
O15169	O15169	2	binding	up-regulates activity	0.2	The axin dix domain has a novel structural fold largely composed of beta-strands that engage in head-to-tail self-interaction to form filaments in the crystal	SIGNOR-155218
O43318	O43318	2	phosphorylation	up-regulates activity	0.2	Analyses of phosphorylation site mutants of the activation segment indicate that autophosphorylation of Ser-192 precedes TAB1 phosphorylation and is followed by sequential phosphorylation of Thr-178, Thr-187, and finally Thr-184. Finally, we present a model for the chronological order of events governing TAB1-induced TAK1 autoactivation.	SIGNOR-227544
P53350	Q8TF76	2	binding	up-regulates activity	0.2	Phosphorylation by Cyclin B-Cdk1 allows Haspin to bind Plk1-PBD. Phosphorylation of Haspin at T128 and Plk1 target sites is required for full H3T3ph generation and normal Aurora B localization in mitosis.	SIGNOR-275420
P11362	P11362	2	phosphorylation	up-regulates	0.2	Fgfr signaling is under the control of tyrosine phosphorylation to elicit activation of cellular signaling cascades. Ligand binding induces receptor dimerization and transphosphorylation. Fgfr1 contains eleven tyrosine residues (tyr154, tyr280, tyr307, tyr463, tyr585, tyr605, tyr653, tyr654, tyr730 and tyr766), some of which are directly involved regulating the activity of the receptor and others bind to activate substrates leading to the activation of various transduction pathways.	SIGNOR-98626
Q99683	Q99683	2	phosphorylation	up-regulates activity	0.2	Reporter gene assays showed that all three identified in vitro autophosphorylation sites (thr813, thr838, thr842) regulate ask1 signalingmutation of thr838 drastically reduced reporter gene activity when compared to unstimulated control levels. Interestingly, mutation of the other two sites also provided a significant reduction in ask1 function (figure 6a), suggesting that autophosphorylation at the residues thr842 and thr813 regulates ask1 signaling.	SIGNOR-158431
P08631	P08631	2	phosphorylation	up-regulates activity	0.2	Hck transiently expressed in human embryonic kidney 293T cells was found to be phosphorylated at Tyr-29 and Tyr-388, proving that Hck can also undergo autophosphorylation at both sites in vivo. autophosphorylation of Tyr-29 contributes significantly to the activation of Hck.	SIGNOR-251266
P35968	P35968	2	phosphorylation	up-regulates	0.2	Binding of vegf to the receptor induces dimerisation and autophosphorylation of specific intracellular tyrosine residues. Activation of intracellular cascades results in proliferation, migration, survival and increased permeability.	SIGNOR-157093
O95382	O95382	2	phosphorylation	up-regulates activity	0.2	These results suggested that the induction of ASK2 phosphorylation in the presence of ASK1 is the consequence of autophosphorylation of ASK2. ASK1 thus appears to not only support the effective protein expression but also confer the kinase activity to ASK2.	SIGNOR-260774
P19525	P19525	2	phosphorylation	up-regulates activity	0.2	PKR autophosphorylates on Y101, Y162, and Y293 in vitro. Site-specific tyrosine phosphorylation is essential for efficient dsRNA-binding, dimerization, kinase activation and eIF2alpha phosphorylation of PKR.	SIGNOR-260784
P54762	P54762	2	phosphorylation	up-regulates activity	0.2	Co-immunoprecipitation was used to confirm the interaction of Grb7 with the cytoplasmic domain of EphB1 as well as the full-length receptor in intact cells. This interaction is mediated by the SH2 domain of Grb7 and requires tyrosine autophosphorylation of EphB1. We also found that EphB1 could phosphorylate Grb7 and mutation of either Tyr-928 or Tyr-594 to Phe decreased this activity.	SIGNOR-251123
P43320	P43320	2	binding	up-regulates activity	0.2	βB2-crystallin is the major component of β-crystallin and is a dimer at low concentrations. At high concentrations or in the lens, βB2-crystallin forms hetero-oligomers with other β-crystallins. These oligomeric β-crystallins further participate in the formation of a supramolecular assembly that is important in lens function-lens transparency.	SIGNOR-252154
P49840	P49840	2	phosphorylation	up-regulates	0.2	Gsk3a is activated by phosphorylation at tyr-279.	SIGNOR-180035
P49674	P49674	2	phosphorylation	down-regulates activity	0.2	Amino acids Ser-323, Thr-325, Thr-334, Thr-337, Ser-368, Ser-405, Thr-407, and Ser-408 in the carboxyl-terminal tail of CKIepsilon were identified as probable in vivo autophosphorylation sites. A recombinant CKIepsilon protein with serine and threonine to alanine mutations eliminating these autophosphorylation sites was 8-fold more active than wild-type CKIepsilon using IkappaBalpha as a substrate. T	SIGNOR-250813
O75582	O75582	2	phosphorylation	up-regulates activity	0.2	Msk1 can autophosphorylate on at least six sites: ser-212, ser-376, ser-381, ser-750, ser-752 and ser-758. Of these sites, the n-terminal t-loop residue ser-212 and the 'hydrophobic motif' ser-376 are phosphorylated by the c-terminal kinase domain of msk1, and their phosphorylation is essential for the catalytic activity of the n-terminal kinase domain of msk1 and therefore for the phosphorylation of msk1 substrates in vitro.	SIGNOR-131395
P18075	P18075	2	binding	up-regulates	0.2	Bmps are dimeric proteins with a single inter-chain disulfide bond. The dimeric conformation is an absolute requirement for the biological action and interac- tion with receptors	SIGNOR-236172
Q13153	Q13153	2	phosphorylation	up-regulates activity	0.2	Cdc42 and Rac1 cause alpha-PAK autophosphorylation and kinase activation.	SIGNOR-250219
Q9UPZ9	Q9UPZ9	2	phosphorylation	up-regulates	0.2	Ick is activated by dual phosphorylation of the tdy motif. Phosphorylation of tyr-159 in the tdy motif requires ick autokinase activity	SIGNOR-138424
Q9NX47	Q9NX47	2	polyubiquitination	down-regulates quantity by destabilization	0.2	Rapid degradation of MITOL by autoubiquitination activity. Taken together, these results suggested that MITOL strictly controls its protein expression level by rapid degradation of MITOL through the PHD-dependent autoubiquitination activity.	SIGNOR-271895
Q02952	P17612	2	phosphorylation	up-regulates activity	0.2	Following receptor activation, gravin binding to the receptor increases, a process dependent upon PKA-catalyzed phosphorylation of two canonical PKA sites (Ser696–698 and Ser772) located within the AKAP domain of gravin.	SIGNOR-271844
O76039	O76039	2	phosphorylation	up-regulates activity	0.2	Furthermore, we show that CDKL5 can self-associate and mediate the phosphorylation of its own TEY (Thr-Glu-Tyr) motif.	SIGNOR-262289
Q9P286	Q9P286	2	phosphorylation	up-regulates activity	0.2	Active form of Cdc42, but not Rac1 and Rho, protein was able to activate the purified GST-Pak5 autophosphorylation and kinase activity. Mutations of Pak5, which disrupted the interaction of Cdc42 and Pak5, also abolished the induction of autophosphorylation. The H19L/H22L mutant of Pak5 was insensitive to the Cdc42-induced autophosphorylation.	SIGNOR-250248
P41162	P41162	2	transcriptional regulation	down-regulates quantity by repression	0.2	ETV3 target genes including etv3, ddx20, and dusp6 provide negative feedback regulation of ETV3 production and activity. Negative feedback along with constitutive instability may serve to tightly regulate ETV3 abundance. Our date suggest that phosphorylation by ERK2 relieves repression by ETV3, allowing activation of cell cycle control genes including myc, components of the NF-κB pathway, and genes required form RNA processing and translation.	SIGNOR-262778
Q99759	O43379	2	relocalization	up-regulates activity	0.2	In the WT brain, the WDR62 scaffold organizes a protein complex including MEKK3, MKK4/7, and JNK1 to control NPC development during corticogenesis	SIGNOR-271717
P17948	P17948	2	phosphorylation	up-regulates	0.2	Receptor tyrosine phosphorylation is crucial for signal transduction by creating high affinity binding sites for src homology 2 domain-containing molecules. By expressing the intracellular domain of flt-1/vascular endothelial growth factor receptor-1 in the baculosystem, we identified two major tyrosine phosphorylation sites at tyr-1213 and tyr-1242 and two minor tyrosine phosphorylation sites at tyr-1327 and tyr-1333 in this receptor.	SIGNOR-59762
P07332	P07332	2	phosphorylation	up-regulates	0.2	Substitution of kinase domain tyrosine residues 713 or 811 with phenylalanine resulted in a loss of the 10- and 4-kda phosphopeptides, respectively, identifying these tyrosines as in vitro autophosphorylation sites. Cnbr cleavage analysis of fes isolated from 32po4-labeled 293t cells showed that tyr-713 and tyr-811 are also autophosphorylated in vivo. . Mutagenesis of tyr-713 reduced both autophosphorylation of tyr-811 and transphosphorylation of bcr, a recently identified fes substrate, supporting a major regulatory role for tyr-713.	SIGNOR-42655
P28482	P28482	2	phosphorylation	up-regulates activity	0.2	Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation.\|	SIGNOR-249415
P00558	P00558	2	phosphorylation	up-regulates activity	0.2	PGK1 functions not only as a glycolytic enzyme but also as a protein kinase intermolecularly autophosphorylating itself at Y324 for activation.	SIGNOR-277482
P29317	P29317	2	phosphorylation	up-regulates	0.2	The binding of ephrin ligands to eph receptors induces the transphosphorylation of the cytoplasmic domains and initiates kinase activity.Taken together, these results suggest that tyr587, tyr593, tyr771, and tyr734 are likely to be autophospho-rylated in vascular endothelial cells.	SIGNOR-178169
Q9UQM7	Q9UQM7	2	phosphorylation	down-regulates	0.2	After removal of ca2+/calmodulin, the autonomous kinase undergoes a burst of inhibitory autophosphorylation at sites distinct from the autonomy site. Ca(2+)-independent autophosphorylation occurs within the calmodulin binding domain at thr305, thr306, and ser314	SIGNOR-17312
P25445	P25445	2	binding	up-regulates activity	0.2	The fas receptor, upon binding to the fasl, trimerizes	SIGNOR-85991
P43403	P43403	2	phosphorylation	up-regulates activity	0.2	Zap-70 is modified by auto-phosphorylation of various tyrosine residues and is activated by specific phosphorylation of the tyrosine residue y-493	SIGNOR-139098
Q8NEV4	Q8NEV4	2	phosphorylation	down-regulates activity	0.2	We demonstrate by mass spectrometry that Thr-178 and Thr-184 in the kinase domain activation loop and two threonines in the loop 2 region of the motor domain are autophosphorylated (Thr-908 and Thr-919) \| Thus, the phosphorylation sites in loop 2 (Thr-908 and Thr-919) are likely responsible for the down-regulation of MYO3A motor activity observed in our current and previous work	SIGNOR-260923
P42338	P42338	2	phosphorylation	down-regulates activity	0.2	Autophosphorylation sites of both pi3k isoforms were mapped to c-terminal serine residues of the catalytic p110 subunit (i.e. serine 1070 of p110 beta and serine 1101 of p110 gamma). autophosphorylation of p110 beta On serine 1070 results in down-regulation of the lipid kinase activity of pi3k beta	SIGNOR-96776
Q9H211	Q9H211	2	binding	up-regulates activity	0.2	We further show that Cdc6 physically associates with Cdt1 via its N-terminal noncatalytic domain, a region we had previously shown to be essential for Cdc6 function.	SIGNOR-261682
Q96RR4	Q96RR4	2	phosphorylation	up-regulates	0.2	It has been proposed that a major consequence of relief from autoinhibition is autophosphorylation of thr-482, a post-translational change that likely contributes to the increased autonomous activity of camkk2	SIGNOR-198107
Q9NZJ5	Q9NZJ5	2	phosphorylation	up-regulates	0.2	We show that perk is capable of autophosphorylating on tyrosine residues in vitro and in vivo. We further show that tyrosine 615, which is embedded in a highly conserved region of the kinase domain of perk, is essential for autocatalytic activity.	SIGNOR-159156
Q15208	Q15208	2	phosphorylation	up-regulates	0.2	We found that ndr1 autophosphorylates in vitro predominantly on ser-281 and to a lesser extent on thr-74 and thr-444. All of these residues proved to be crucial also for ndr1 activity in vivo	SIGNOR-96687
Q9NWZ3	Q9NWZ3	2	phosphorylation	up-regulates activity	0.2	We show irak4 autophosphorylation occurs by an intermolecular reaction and that autophosphorylation is required for full catalytic activity of the kinase. Phosphorylation of any two of the residues thr-342, thr-345, and ser-346 is required for full activity	SIGNOR-204657
Q08881	Q08881	2	phosphorylation	up-regulates activity	0.2	In this study, we present evidence for another mode of regulation for itk, the autophosphorylation of tyr-180 in the src homology 3 (sh3) domain.	SIGNOR-103170
P05556	Q12809	2	binding	up-regulates activity	0.2	One such mechanism is operant in colorectal cancer (CRC) cells. On integrin-dependent CRC cell adhesion, the Kv11.1/β1 integrin complex recruits the PI3K p85 subunit, which stimulates AKT phosphorylation and thus regulates autophagy	SIGNOR-277613
P08581	P08581	2	phosphorylation	up-regulates	0.2	Previous work has shown that autophosphorylation of p190met enhances its enzymatic activity and that the major phosphorylation site is tyr1235, located in the catalytic domainonly the replacement of both tyr1234 and tyr1235 yielded a mutant which completely lost the ability to be activated by autophosphorylation	SIGNOR-37727
P18031	P18031	2	dephosphorylation	down-regulates activity	0.2	Tyrosine residues 66, 152 and/or 153 of PTP1B are phosphorylated by the activated insulin receptor and are also necessary for formation of the PTP1B:insulin receptor complex\| Furthermore, tyrosine phosphorylation of PTP1B by the insulin receptor tyrosine kinase increases the catalytic activity of PTP1B\|These results suggest that PTP1B can dephosphorylate itself under in vitro conditions.	SIGNOR-248423
P35916	P35916	2	phosphorylation	up-regulates activity	0.2	Trans-phosphorylation of activated, dimerized receptor tyrosine kinases is known to be critical for the regulation of kinase activity and for receptor interaction with signal transduction molecules. In this study, we have identified five tyrosyl phosphorylation sites in the vegfr-3 carboxyl-terminal tail.	SIGNOR-104088
Q8IVH8	Q8IVH8	2	phosphorylation	up-regulates	0.2	We identify a transautophosphorylation site in the map4k3 kinase activation segment (ser170) that is required for map4k3 activity and its activation of mtorc1 signaling.	SIGNOR-164103
Q9BX84	Q9BX84	2	phosphorylation	down-regulates activity	0.2	Autophosphorylation of Threonine1851 in the Kinase Domain Is Essential for the Inhibitory Effect of RACK1	SIGNOR-260922
P51617	P51617	2	phosphorylation	up-regulates activity	0.2	In vitro the IRAK-1 activation loop is a good substrate for IRAK-4, and that T387 and S376 are the main sites of phosphorylation by both IRAK-1 and IRAK-4.	SIGNOR-251330
P31749	P31749	2	phosphorylation	up-regulates activity	0.2	Autophosphorylation of Akt on Thr-72 and Ser-246 appeared to require prior phosphorylation of Akt on Thr-308 and Ser-473. Compared with wild-type Akt, Akt/T72A/S246A mutant exhibited markedly reduced basal Akt kinase activity and response to cellular stimulation by insulin-like growth factor-1, and also conferred less cellular resistance to doxorubicin-induced apoptosis.	SIGNOR-276055
Q05397	Q05397	2	phosphorylation	up-regulates	0.2	Fak autophosphorylation site, tyr397. / extracellular matrix (ecm)-induced autophosphorylation of fak on tyr397 creates a high affinity binding site for the sh2 domain of c-src, and mutation (tyr to phe) of this residue inhibits association	SIGNOR-77434
Q07912	Q07912	2	phosphorylation	up-regulates	0.2	Purified ack1 undergoes autophosphorylation, and autophosphorylation enhances kinase activity. We identified tyr284 in the activation loop of ack1 as the primary autophosphorylation site using mass spectrometry.	SIGNOR-118201
P00519	P00519	2	phosphorylation	up-regulates activity	0.2	We demonstrate here that autophosphorylation of ABL1 is intermolecular and stimulates Abl catalytic activity.	SIGNOR-260781
Q9H2X6	Q9H2X6	2	phosphorylation	up-regulates activity	0.2	Here, we deciphered the molecular mechanism of HIPK2 activation and show its relevance for DNA damage-induced apoptosis in cellulo and in vivo. HIPK2 autointeracts and site-specifically autophosphorylates upon DNA damage at Thr880/Ser882. Autophosphorylation regulates HIPK2 activity and mutation of the phosphorylation-acceptor sites deregulates p53 Ser46 phosphorylation and apoptosis in cellulo.	SIGNOR-276601
Q8NHY2	Q8NHY2	2	polyubiquitination	down-regulates quantity by destabilization	0.2	MTA1 destabilizes COP1 by promoting its autoubiquitination. in addition to polyubiquitination of its substrates, COP1 also catalyzes its autoubiquitination for degradation as a part of an autoregulatory mechanism	SIGNOR-271893
Q8NER1	P05771	2	phosphorylation	up-regulates activity	0.2	PKCβII causes the downregulation of TRPV1 by phosphorylating the channel. The increased threonine phosphorylation was substantially reduced by mutating Thr705, showing that Thr705 is indeed a major PKCβII phosphorylation site.	SIGNOR-276638
Q8WY64	Q8WY64	2	ubiquitination	down-regulates quantity by destabilization	0.2	MIR contains, beside the ERM domain, a RING zinc finger region. The present study shows that the ubiquitin ligase activity of the RING can also be directed towards the protein itself indicating that the degradation of MIR can be regulated by autoubiquitination.	SIGNOR-271480
O43293	O43293	2	phosphorylation	up-regulates	0.2	Mutational analysis showed that phosphorylation of thr180 in the kinase activation t-loop, thr225 in the substrate-binding groove, and thr265 in kinase subdomain x is essential for full zipk autophosphorylation and activity toward exogenous substrates.	SIGNOR-132463
Q6PHR2	Q6PHR2	2	phosphorylation	up-regulates activity	0.2	We show that ULK3 autophosphorylation occurs at four serine residues (Ser-300, Ser-350, Ser-384, and Ser-464) situated outside of the KD \| Thus, autophosphorylation of ULK3 may involve conformational changes resulted in exposure of CTD to KD and consequently in generation of the catalytically active kinase.	SIGNOR-260794
P35226	P35226	2	transcriptional regulation	up-regulates quantity by expression	0.2	Here, we report that BMI1 autoactivates its own promoter via an E-box present in its promoter.	SIGNOR-245344
Q9Y6R4	Q9Y6R4	2	phosphorylation	up-regulates activity	0.2	Gadd45 binding also induced mtk1 dimerization via a dimerization domain containing a coiled-coil motif, which is essential for the trans autophosphorylation of mtk1 at thr-1493 in the kinase activation loop.	SIGNOR-152408
P01106	Q9Y4D8	2	ubiquitination	down-regulates quantity by destabilization	0.2	We identified several E3 ligases as strong candidates responsible for AR and MYC protein loss as HECTD4, MYCBP2, and TRIM49. HECTD4 and MYCBP2 target AR and MYC for degradation while TRIM49 appears to promote AR and MYC stability. We have shown that these E3 ligases in turn are directly regulated by MYC. MYC in turn represses the expression of ubiquitin ligases, HECTD4 and MYCBP2 that promote AR and MYC protein degradation, further suppressing MYC and AR in a feed forward loop.	SIGNOR-267146
O43683	O43683	2	phosphorylation	up-regulates activity	0.2	Conversely, Bub1 is an active kinase regulated by intra-molecular phosphorylation at the P+1 loop.	SIGNOR-277186

P01137

2

binding

up-regulates activity

0.2

The active form of TGF-beta is a dimer stabilized by hydrophobic interactions and usually further strengthened by an intersubunit disulfide bridge.

SIGNOR-148605

P46020

2

phosphorylation

up-regulates activity

0.2

Phk is activated in vitro by autophosphorylation. Ser1018 and at least three of the other six serine residues (Ser972, -985, and -1007) can be phosphorylated in vitro by Phk itself (autophosphorylation)

SIGNOR-250282

Q13627

2

phosphorylation

up-regulates

0.2

Mirk kinase is activated by autophosphorylation on tyrosine at the y271/y273 site

SIGNOR-79760

P43405

2

phosphorylation

up-regulates activity

0.2

These represented sites of tyrosine phosphorylation previously identified from the study of in vitro autophosphorylated Syk. Phosphorylation was observed on peptides corresponding to Tyr130, Tyr317, Tyr342, Tyr346, Tyr519, and Tyr520

SIGNOR-246621

Q15831

2

phosphorylation

up-regulates activity

0.2

It was shown that thr336 and thr366 are the major autophosphorylation sites of mouse lkb1 (sapkota et al., 2002). We confirmed these data on the human orthologues thr336 and thr363. Moreover, the enhanced stoichiometry of lkb1 autophosphorylation by strad enabled us to identify two novel sites: thr185 and thr402. We show that increased lkb1 autophosphorylation of all sites correlates with the activation of its catalytic activity.

SIGNOR-101844

Q9NYL2

2

phosphorylation

up-regulates

0.2

Ionizing radiation induces mrk autophosphorylation and activation. Within the mrk kinase loop between the dfg (subdomain vii) and ape (subdomain viii) residues, there are three conserved threonine/serine residues (thr161, thr162, and ser165) that are important for activation.

SIGNOR-128581

P29466

Q96EP0

2

polyubiquitination

up-regulates activity

0.2

HOIP forms a constitutive interaction with caspase-1 and mediates the linear ubiquitination of the CARD pro-domain. Upon engagement of apoptosis, caspase-1 and caspase-8 cleave HOIP at Asp-348 and Asp-387, limiting the ability of LUBAC to ubiquitinate substrates.

SIGNOR-272191

P15056

2

phosphorylation

down-regulates activity

0.2

We previously identified that BRAFWT can autophosphorylate its P-loop (Ser-465/Ser-467) to inactivate itself in the absence of native substrate MEK

SIGNOR-277498

O96017

2

phosphorylation

up-regulates activity

0.2

Thus, activation of chk2 in irradiated cells may occur through oligomerization of chk2 via binding of the thr-68-phosphorylated region of one chk2 to the fha domain of another. Oligomerization of chk2 may therefore increase the efficiency of trans-autophosphorylation resulting in the release of active chk2 monomers that proceed to enforce checkpoint control in irradiated cells.

SIGNOR-116135

Q05513

2

phosphorylation

up-regulates

0.2

Our findings suggest that insulin, via pip(3), provokes increases in pkc-zeta enzyme activity through (a) pdk-1-dependent t410 loop phosphorylation, (b) t560 autophosphorylation

SIGNOR-85505

Q96SB4

2

phosphorylation

up-regulates

0.2

We found that activated akt binds and induces srpk1 autophosphorylation because akt-mediated phosphorylation depends on the kinase activity of srpk1

SIGNOR-197989

O43353

2

phosphorylation

up-regulates activity

0.2

In summary, our results indicate that s176 is a regulatory autophosphorylation site for rip2 and that s176 phosphorylation can be used to monitor the activation state of rip2.

SIGNOR-229701

P30530

2

phosphorylation

up-regulates activity

0.2

Our data showed that various receptor substrates are at least associated with the C-terminal tyrosine pY821. Two additional potential autophosphorylation sites (pY866 and pY779) may play a minor role in binding of eector proteins

SIGNOR-250593

Q16611

2

binding

up-regulates

0.2

Allosteric activation of bak induces its intramembranous oligomerization into a proposed pore for cytochrome c efflux

SIGNOR-105203

P35269

2

phosphorylation

down-regulates

0.2

We show that tfiifalpha possesses a serine/threonine kinase activity, allowing an autophosphorylation of the two residues at position serine 385 and threonine 389. Mutation analysis strongly suggests that autophosphorylation of both sites regulates the transcription elongation process.

SIGNOR-69767

P37173

2

phosphorylation

down-regulates activity

0.2

Ser213, in the membrane-proximal segment outside the kinase domain, undergoes intra-molecular autophosphorylation which is essential for the activation of TbetaRII kinase activity, activation of TbetaRI and TGF-beta-induced growth inhibition. In contrast, phosphorylation of Ser409 and Ser416, located in a segment corresponding to the substrate recognition T-loop region in a three-dimensional structural model of protein kinases, is enhanced by receptor dimerization and can occur via an intermolecular mechanism. Phosphorylation of Ser409 is essential for TbetaRII kinase signaling, while phosphorylation of Ser416 inhibits receptor function.

SIGNOR-246737

Q15759

2

phosphorylation

up-regulates activity

0.2

P38β Mitogen-Activated Protein Kinase Modulates Its Own Basal Activity by Autophosphorylation of the Activating Residue Thr180 and the Inhibitory Residues Thr241 and Ser261

SIGNOR-277216

Q13882

2

phosphorylation

up-regulates

0.2

Autophosphorylation increases enzyme activity of wild-type brk but not of a y342a mutant form of brk.

SIGNOR-90604

Q15418

2

phosphorylation

up-regulates activity

0.2

Herein, we demonstrate that the n-terminal kinase domain (ntk) of rsk1 is necessary for interactions with pkarialpha. Substitution of the activation loop phosphorylation site (ser-221) in the ntk with the negatively charged asp residue abrogated the association between rsk1 and pkarialpha.

SIGNOR-162681

Q13239

P10721

2

phosphorylation

down-regulates activity

0.2

Oncogenic c-Kit-D816V phosphorylates SLAP on residues Y120, Y258 and Y273. Mutation of the SLAP tyrosine phosphorylation sites rescues its activity

SIGNOR-263141

O60674

2

phosphorylation

up-regulates

0.2

Autophosphorylation of jak2 on tyrosines 221 and 570 regulates its activity with phosphorylation of tyrosine 221 increasing kinase activity

SIGNOR-236506

Q13546

2

phosphorylation

up-regulates activity

0.2

These data suggest that Ser14/15, Ser20, Ser161 and Ser166 represent autophosphorylation sites in vitro, detected in the RIP1 kinase assay (Fig. 1)

SIGNOR-276159

Q8TD19

2

phosphorylation

up-regulates

0.2

We find that the interaction of lc8 with nek9 depends on a (k/r)xtqt motif adjacent to the nek9 c-terminal coiled coil motif, results in nek9 multimerization, and increases the rate of nek9 autoactivation. Lc8 binding to nek9 is regulated by nek9 activity through the autophosphorylation of ser(944), a residue immediately n-terminal to the (k/r)xtqt motif.

SIGNOR-173026

P54764

2

phosphorylation

up-regulates activity

0.2

Two dimensional phosphopeptide mapping and site-directed mutagenesis defined juxtamembrane residue Y602 as a major site of in vitro autophosphorylation in Sek, whilst Y596 was phosphorylated to a lower stoichiometry.

SIGNOR-251118

Q9H4A3

2

phosphorylation

up-regulates

0.2

We demonstrate that wnk1 is rapidly activated and phosphorylated at multiple residues after exposure of cells to hyperosmotic conditions and that activation is mediated by the phosphorylation of its t-loop ser382 residue, possibly triggered by a transautophosphorylation reaction.

SIGNOR-160850

Q9H9S0

2

transcriptional regulation

up-regulates quantity by expression

0.2

We conclude that the Nanog enhancer activity is regulated by both Sall4 and Nanog.

SIGNOR-266080

O14757

2

phosphorylation

up-regulates activity

0.2

This suggests that Ser296 is probably one of the sites autophosphorylated when Chk1 is fully activated [21], despite the sequence surrounding Ser296 (FSKHIQS296NL) being only weakly related to the optimal Chk1-recognition motif (M/I/L/V)-X-(R/K)-X-X-(S/T), where (S/T) is the phosphorylated residue

SIGNOR-219240

P22607

2

phosphorylation

up-regulates activity

0.2

Ligand stimulation leads to autophosphorylation of fgfr3 the absence of y577 (3y-577f) or y760 (3y-760f) resulted in a modest decrease in activity.

SIGNOR-106726

P00533

2

phosphorylation

up-regulates activity

0.2

EGFR possesses three major and two minor tyrosine autophosphorylation sites located at Y1068, Y1148, Y1173, and at Y992 and Y1086 respectively. In addition, EGFR Y1114 is preceded by glutamic acid (Figure 1), which should be preferred by the EGFR kinase as indicated in previous work

SIGNOR-236527

P36888

2

phosphorylation

up-regulates

0.2

Previously we reported that flt3 with itd (flt3/itd) formed a homodimer and was autophosphorylated on tyrosine residuewe examined the role of tyr residues (y589, y591, y597 and y599) in the jm domain in the activation of flt3. In wt-flt3, these tyr residues were important for the fl-dependent activation

SIGNOR-117575

Q9Y653

2

cleavage

up-regulates activity

0.2

Like many other adhesion GPCRs, GPR56 is cleaved via a GPCR autoproteolysis-inducing (GAIN) domain into N- and C-terminal fragments (GPR56N and GPR56C); | We demonstrate that ligand binding releases GPR56N from the membrane-bound GPR56C and triggers the association of GPR56C with lipid rafts and RhoA activation.

SIGNOR-253980

Q16649

2

binding

up-regulates activity

0.2

E4BP4, ATF-6, OASIS, and XBP-1 all formed strong homodimeric associations on the array Transcription factor dimerization can increase the selectivity of protein-DNA interactions and generate a large amount of DNA binding diversity from a relatively small number of proteins

SIGNOR-224248

P60484

2

dephosphorylation

up-regulates activity

0.2

Overall, our results suggest that PTEN autodephosphorylation may be a critical event in this process; thus a major protein substrate for PTEN may be PTEN itself.|Various studies have demonstrated that PTEN is itself a phosphoprotein, and that the major sites of phosphorylation are found in an acidic stretch (DHYRYSDTTDSDPENE) near the C-terminus [1]. This prompted us to consider whether PTEN may autodephosphorylate these sites

SIGNOR-248545

P07947

2

phosphorylation

up-regulates activity

0.2

Autophosphorylation of Src and Yes blocks their inactivation by Csk phosphorylation

SIGNOR-247014

P08069

2

phosphorylation

up-regulates activity

0.2

Insulin and insulin-like growth factor (igf-i) receptors are heterotetrameric proteins consisting of two alpha-and two beta-subunits and members of the transmembrane tyrosine kinase receptors. Specific ligand binding to the receptor triggers a cascade of intracellular events, which begins with autophosphorylation of several tyrosine residues of the beta-subunit of the receptor.

SIGNOR-26582

P45985

2

phosphorylation

up-regulates activity

0.2

Ser221 and, to a lesser extent, Thr225 in MKK4 as necessary sites for basal and MEKK-induced autophosphorylation and activation of MKK4.

SIGNOR-251420

Q13188

2

phosphorylation

up-regulates

0.2

Consistent with previous studies, sts alone induces mst2 cleavage and autophosphorylation of thr180, an indicator of mst2 activation, as well as apoptosis.

SIGNOR-164310

P13861

2

phosphorylation

up-regulates activity

0.2

RII subunit containing the 'autophosphorylation' site (Ser-95)

SIGNOR-250073

P01019-PRO_0000032457

Q9BYF1

2

cleavage

up-regulates activity

0.2

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

SIGNOR-260222

P27361

2

phosphorylation

up-regulates activity

0.2

Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation.|

SIGNOR-249471

O15169

2

binding

up-regulates activity

0.2

The axin dix domain has a novel structural fold largely composed of beta-strands that engage in head-to-tail self-interaction to form filaments in the crystal

SIGNOR-155218

O43318

2

phosphorylation

up-regulates activity

0.2

Analyses of phosphorylation site mutants of the activation segment indicate that autophosphorylation of Ser-192 precedes TAB1 phosphorylation and is followed by sequential phosphorylation of Thr-178, Thr-187, and finally Thr-184. Finally, we present a model for the chronological order of events governing TAB1-induced TAK1 autoactivation.

SIGNOR-227544

P53350

Q8TF76

2

binding

up-regulates activity

0.2

Phosphorylation by Cyclin B-Cdk1 allows Haspin to bind Plk1-PBD. Phosphorylation of Haspin at T128 and Plk1 target sites is required for full H3T3ph generation and normal Aurora B localization in mitosis.

SIGNOR-275420

P11362

2

phosphorylation

up-regulates

0.2

Fgfr signaling is under the control of tyrosine phosphorylation to elicit activation of cellular signaling cascades. Ligand binding induces receptor dimerization and transphosphorylation. Fgfr1 contains eleven tyrosine residues (tyr154, tyr280, tyr307, tyr463, tyr585, tyr605, tyr653, tyr654, tyr730 and tyr766), some of which are directly involved regulating the activity of the receptor and others bind to activate substrates leading to the activation of various transduction pathways.

SIGNOR-98626

Q99683

2

phosphorylation

up-regulates activity

0.2

Reporter gene assays showed that all three identified in vitro autophosphorylation sites (thr813, thr838, thr842) regulate ask1 signalingmutation of thr838 drastically reduced reporter gene activity when compared to unstimulated control levels. Interestingly, mutation of the other two sites also provided a significant reduction in ask1 function (figure 6a), suggesting that autophosphorylation at the residues thr842 and thr813 regulates ask1 signaling.

SIGNOR-158431

P08631

2

phosphorylation

up-regulates activity

0.2

Hck transiently expressed in human embryonic kidney 293T cells was found to be phosphorylated at Tyr-29 and Tyr-388, proving that Hck can also undergo autophosphorylation at both sites in vivo. autophosphorylation of Tyr-29 contributes significantly to the activation of Hck.

SIGNOR-251266

P35968

2

phosphorylation

up-regulates

0.2

Binding of vegf to the receptor induces dimerisation and autophosphorylation of specific intracellular tyrosine residues. Activation of intracellular cascades results in proliferation, migration, survival and increased permeability.

SIGNOR-157093

O95382

2

phosphorylation

up-regulates activity

0.2

These results suggested that the induction of ASK2 phosphorylation in the presence of ASK1 is the consequence of autophosphorylation of ASK2. ASK1 thus appears to not only support the effective protein expression but also confer the kinase activity to ASK2.

SIGNOR-260774

P19525

2

phosphorylation

up-regulates activity

0.2

PKR autophosphorylates on Y101, Y162, and Y293 in vitro. Site-specific tyrosine phosphorylation is essential for efficient dsRNA-binding, dimerization, kinase activation and eIF2alpha phosphorylation of PKR.

SIGNOR-260784

P54762

2

phosphorylation

up-regulates activity

0.2

Co-immunoprecipitation was used to confirm the interaction of Grb7 with the cytoplasmic domain of EphB1 as well as the full-length receptor in intact cells. This interaction is mediated by the SH2 domain of Grb7 and requires tyrosine autophosphorylation of EphB1. We also found that EphB1 could phosphorylate Grb7 and mutation of either Tyr-928 or Tyr-594 to Phe decreased this activity.

SIGNOR-251123

P43320

2

binding

up-regulates activity

0.2

βB2-crystallin is the major component of β-crystallin and is a dimer at low concentrations. At high concentrations or in the lens, βB2-crystallin forms hetero-oligomers with other β-crystallins. These oligomeric β-crystallins further participate in the formation of a supramolecular assembly that is important in lens function-lens transparency.

SIGNOR-252154

P49840

2

phosphorylation

up-regulates

0.2

Gsk3a is activated by phosphorylation at tyr-279.

SIGNOR-180035

P49674

2

phosphorylation

down-regulates activity

0.2

Amino acids Ser-323, Thr-325, Thr-334, Thr-337, Ser-368, Ser-405, Thr-407, and Ser-408 in the carboxyl-terminal tail of CKIepsilon were identified as probable in vivo autophosphorylation sites. A recombinant CKIepsilon protein with serine and threonine to alanine mutations eliminating these autophosphorylation sites was 8-fold more active than wild-type CKIepsilon using IkappaBalpha as a substrate. T

SIGNOR-250813

O75582

2

phosphorylation

up-regulates activity

0.2

Msk1 can autophosphorylate on at least six sites: ser-212, ser-376, ser-381, ser-750, ser-752 and ser-758. Of these sites, the n-terminal t-loop residue ser-212 and the 'hydrophobic motif' ser-376 are phosphorylated by the c-terminal kinase domain of msk1, and their phosphorylation is essential for the catalytic activity of the n-terminal kinase domain of msk1 and therefore for the phosphorylation of msk1 substrates in vitro.

SIGNOR-131395

P18075

2

binding

up-regulates

0.2

Bmps are dimeric proteins with a single inter-chain disulfide bond. The dimeric conformation is an absolute requirement for the biological action and interac- tion with receptors

SIGNOR-236172

Q13153

2

phosphorylation

up-regulates activity

0.2

Cdc42 and Rac1 cause alpha-PAK autophosphorylation and kinase activation.

SIGNOR-250219

Q9UPZ9

2

phosphorylation

up-regulates

0.2

Ick is activated by dual phosphorylation of the tdy motif. Phosphorylation of tyr-159 in the tdy motif requires ick autokinase activity

SIGNOR-138424

Q9NX47

2

polyubiquitination

down-regulates quantity by destabilization

0.2

Rapid degradation of MITOL by autoubiquitination activity. Taken together, these results suggested that MITOL strictly controls its protein expression level by rapid degradation of MITOL through the PHD-dependent autoubiquitination activity.

SIGNOR-271895

Q02952

P17612

2

phosphorylation

up-regulates activity

0.2

Following receptor activation, gravin binding to the receptor increases, a process dependent upon PKA-catalyzed phosphorylation of two canonical PKA sites (Ser696–698 and Ser772) located within the AKAP domain of gravin.

SIGNOR-271844

O76039

2

phosphorylation

up-regulates activity

0.2

Furthermore, we show that CDKL5 can self-associate and mediate the phosphorylation of its own TEY (Thr-Glu-Tyr) motif.

SIGNOR-262289

Q9P286

2

phosphorylation

up-regulates activity

0.2

Active form of Cdc42, but not Rac1 and Rho, protein was able to activate the purified GST-Pak5 autophosphorylation and kinase activity. Mutations of Pak5, which disrupted the interaction of Cdc42 and Pak5, also abolished the induction of autophosphorylation. The H19L/H22L mutant of Pak5 was insensitive to the Cdc42-induced autophosphorylation.

SIGNOR-250248

P41162

2

transcriptional regulation

down-regulates quantity by repression

0.2

ETV3 target genes including etv3, ddx20, and dusp6 provide negative feedback regulation of ETV3 production and activity. Negative feedback along with constitutive instability may serve to tightly regulate ETV3 abundance. Our date suggest that phosphorylation by ERK2 relieves repression by ETV3, allowing activation of cell cycle control genes including myc, components of the NF-κB pathway, and genes required form RNA processing and translation.

SIGNOR-262778

Q99759

O43379

2

relocalization

up-regulates activity

0.2

In the WT brain, the WDR62 scaffold organizes a protein complex including MEKK3, MKK4/7, and JNK1 to control NPC development during corticogenesis

SIGNOR-271717

P17948

2

phosphorylation

up-regulates

0.2

Receptor tyrosine phosphorylation is crucial for signal transduction by creating high affinity binding sites for src homology 2 domain-containing molecules. By expressing the intracellular domain of flt-1/vascular endothelial growth factor receptor-1 in the baculosystem, we identified two major tyrosine phosphorylation sites at tyr-1213 and tyr-1242 and two minor tyrosine phosphorylation sites at tyr-1327 and tyr-1333 in this receptor.

SIGNOR-59762

P07332

2

phosphorylation

up-regulates

0.2

Substitution of kinase domain tyrosine residues 713 or 811 with phenylalanine resulted in a loss of the 10- and 4-kda phosphopeptides, respectively, identifying these tyrosines as in vitro autophosphorylation sites. Cnbr cleavage analysis of fes isolated from 32po4-labeled 293t cells showed that tyr-713 and tyr-811 are also autophosphorylated in vivo. . Mutagenesis of tyr-713 reduced both autophosphorylation of tyr-811 and transphosphorylation of bcr, a recently identified fes substrate, supporting a major regulatory role for tyr-713.

SIGNOR-42655

P28482

2

phosphorylation

up-regulates activity

0.2

Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation.|

SIGNOR-249415

P00558

2

phosphorylation

up-regulates activity

0.2

PGK1 functions not only as a glycolytic enzyme but also as a protein kinase intermolecularly autophosphorylating itself at Y324 for activation.

SIGNOR-277482

P29317

2

phosphorylation

up-regulates

0.2

The binding of ephrin ligands to eph receptors induces the transphosphorylation of the cytoplasmic domains and initiates kinase activity.Taken together, these results suggest that tyr587, tyr593, tyr771, and tyr734 are likely to be autophospho-rylated in vascular endothelial cells.

SIGNOR-178169

Q9UQM7

2

phosphorylation

down-regulates

0.2

After removal of ca2+/calmodulin, the autonomous kinase undergoes a burst of inhibitory autophosphorylation at sites distinct from the autonomy site. Ca(2+)-independent autophosphorylation occurs within the calmodulin binding domain at thr305, thr306, and ser314

SIGNOR-17312

P25445

2

binding

up-regulates activity

0.2

The fas receptor, upon binding to the fasl, trimerizes

SIGNOR-85991

P43403

2

phosphorylation

up-regulates activity

0.2

Zap-70 is modified by auto-phosphorylation of various tyrosine residues and is activated by specific phosphorylation of the tyrosine residue y-493

SIGNOR-139098

Q8NEV4

2

phosphorylation

down-regulates activity

0.2

We demonstrate by mass spectrometry that Thr-178 and Thr-184 in the kinase domain activation loop and two threonines in the loop 2 region of the motor domain are autophosphorylated (Thr-908 and Thr-919) | Thus, the phosphorylation sites in loop 2 (Thr-908 and Thr-919) are likely responsible for the down-regulation of MYO3A motor activity observed in our current and previous work

SIGNOR-260923

P42338

2

phosphorylation

down-regulates activity

0.2

Autophosphorylation sites of both pi3k isoforms were mapped to c-terminal serine residues of the catalytic p110 subunit (i.e. serine 1070 of p110 beta and serine 1101 of p110 gamma). autophosphorylation of p110 beta On serine 1070 results in down-regulation of the lipid kinase activity of pi3k beta

SIGNOR-96776

Q9H211

2

binding

up-regulates activity

0.2

We further show that Cdc6 physically associates with Cdt1 via its N-terminal noncatalytic domain, a region we had previously shown to be essential for Cdc6 function.

SIGNOR-261682

Q96RR4

2

phosphorylation

up-regulates

0.2

It has been proposed that a major consequence of relief from autoinhibition is autophosphorylation of thr-482, a post-translational change that likely contributes to the increased autonomous activity of camkk2

SIGNOR-198107

Q9NZJ5

2

phosphorylation

up-regulates

0.2

We show that perk is capable of autophosphorylating on tyrosine residues in vitro and in vivo. We further show that tyrosine 615, which is embedded in a highly conserved region of the kinase domain of perk, is essential for autocatalytic activity.

SIGNOR-159156

Q15208

2

phosphorylation

up-regulates

0.2

We found that ndr1 autophosphorylates in vitro predominantly on ser-281 and to a lesser extent on thr-74 and thr-444. All of these residues proved to be crucial also for ndr1 activity in vivo

SIGNOR-96687

Q9NWZ3

2

phosphorylation

up-regulates activity

0.2

We show irak4 autophosphorylation occurs by an intermolecular reaction and that autophosphorylation is required for full catalytic activity of the kinase. Phosphorylation of any two of the residues thr-342, thr-345, and ser-346 is required for full activity

SIGNOR-204657

Q08881

2

phosphorylation

up-regulates activity

0.2

In this study, we present evidence for another mode of regulation for itk, the autophosphorylation of tyr-180 in the src homology 3 (sh3) domain.

SIGNOR-103170

P05556

Q12809

2

binding

up-regulates activity

0.2

One such mechanism is operant in colorectal cancer (CRC) cells. On integrin-dependent CRC cell adhesion, the Kv11.1/β1 integrin complex recruits the PI3K p85 subunit, which stimulates AKT phosphorylation and thus regulates autophagy

SIGNOR-277613

P08581

2

phosphorylation

up-regulates

0.2

Previous work has shown that autophosphorylation of p190met enhances its enzymatic activity and that the major phosphorylation site is tyr1235, located in the catalytic domainonly the replacement of both tyr1234 and tyr1235 yielded a mutant which completely lost the ability to be activated by autophosphorylation

SIGNOR-37727

P18031

2

dephosphorylation

down-regulates activity

0.2

Tyrosine residues 66, 152 and/or 153 of PTP1B are phosphorylated by the activated insulin receptor and are also necessary for formation of the PTP1B:insulin receptor complex| Furthermore, tyrosine phosphorylation of PTP1B by the insulin receptor tyrosine kinase increases the catalytic activity of PTP1B|These results suggest that PTP1B can dephosphorylate itself under in vitro conditions.

SIGNOR-248423

P35916

2

phosphorylation

up-regulates activity

0.2

Trans-phosphorylation of activated, dimerized receptor tyrosine kinases is known to be critical for the regulation of kinase activity and for receptor interaction with signal transduction molecules. In this study, we have identified five tyrosyl phosphorylation sites in the vegfr-3 carboxyl-terminal tail.

SIGNOR-104088

Q8IVH8

2

phosphorylation

up-regulates

0.2

We identify a transautophosphorylation site in the map4k3 kinase activation segment (ser170) that is required for map4k3 activity and its activation of mtorc1 signaling.

SIGNOR-164103

Q9BX84

2

phosphorylation

down-regulates activity

0.2

Autophosphorylation of Threonine1851 in the Kinase Domain Is Essential for the Inhibitory Effect of RACK1

SIGNOR-260922

P51617

2

phosphorylation

up-regulates activity

0.2

In vitro the IRAK-1 activation loop is a good substrate for IRAK-4, and that T387 and S376 are the main sites of phosphorylation by both IRAK-1 and IRAK-4.

SIGNOR-251330

P31749

2

phosphorylation

up-regulates activity

0.2

Autophosphorylation of Akt on Thr-72 and Ser-246 appeared to require prior phosphorylation of Akt on Thr-308 and Ser-473. Compared with wild-type Akt, Akt/T72A/S246A mutant exhibited markedly reduced basal Akt kinase activity and response to cellular stimulation by insulin-like growth factor-1, and also conferred less cellular resistance to doxorubicin-induced apoptosis.

SIGNOR-276055

Q05397

2

phosphorylation

up-regulates

0.2

Fak autophosphorylation site, tyr397. / extracellular matrix (ecm)-induced autophosphorylation of fak on tyr397 creates a high affinity binding site for the sh2 domain of c-src, and mutation (tyr to phe) of this residue inhibits association

SIGNOR-77434

Q07912

2

phosphorylation

up-regulates

0.2

Purified ack1 undergoes autophosphorylation, and autophosphorylation enhances kinase activity. We identified tyr284 in the activation loop of ack1 as the primary autophosphorylation site using mass spectrometry.

SIGNOR-118201

P00519

2

phosphorylation

up-regulates activity

0.2

We demonstrate here that autophosphorylation of ABL1 is intermolecular and stimulates Abl catalytic activity.

SIGNOR-260781

Q9H2X6

2

phosphorylation

up-regulates activity

0.2

Here, we deciphered the molecular mechanism of HIPK2 activation and show its relevance for DNA damage-induced apoptosis in cellulo and in vivo. HIPK2 autointeracts and site-specifically autophosphorylates upon DNA damage at Thr880/Ser882. Autophosphorylation regulates HIPK2 activity and mutation of the phosphorylation-acceptor sites deregulates p53 Ser46 phosphorylation and apoptosis in cellulo.

SIGNOR-276601

Q8NHY2

2

polyubiquitination

down-regulates quantity by destabilization

0.2

MTA1 destabilizes COP1 by promoting its autoubiquitination. in addition to polyubiquitination of its substrates, COP1 also catalyzes its autoubiquitination for degradation as a part of an autoregulatory mechanism

SIGNOR-271893

Q8NER1

P05771

2

phosphorylation

up-regulates activity

0.2

PKCβII causes the downregulation of TRPV1 by phosphorylating the channel. The increased threonine phosphorylation was substantially reduced by mutating Thr705, showing that Thr705 is indeed a major PKCβII phosphorylation site.

SIGNOR-276638

Q8WY64

2

ubiquitination

down-regulates quantity by destabilization

0.2

MIR contains, beside the ERM domain, a RING zinc finger region. The present study shows that the ubiquitin ligase activity of the RING can also be directed towards the protein itself indicating that the degradation of MIR can be regulated by autoubiquitination.

SIGNOR-271480

O43293

2

phosphorylation

up-regulates

0.2

Mutational analysis showed that phosphorylation of thr180 in the kinase activation t-loop, thr225 in the substrate-binding groove, and thr265 in kinase subdomain x is essential for full zipk autophosphorylation and activity toward exogenous substrates.

SIGNOR-132463

Q6PHR2

2

phosphorylation

up-regulates activity

0.2

We show that ULK3 autophosphorylation occurs at four serine residues (Ser-300, Ser-350, Ser-384, and Ser-464) situated outside of the KD | Thus, autophosphorylation of ULK3 may involve conformational changes resulted in exposure of CTD to KD and consequently in generation of the catalytically active kinase.

SIGNOR-260794

P35226

2

transcriptional regulation

up-regulates quantity by expression

0.2

Here, we report that BMI1 autoactivates its own promoter via an E-box present in its promoter.

SIGNOR-245344

Q9Y6R4

2

phosphorylation

up-regulates activity

0.2

Gadd45 binding also induced mtk1 dimerization via a dimerization domain containing a coiled-coil motif, which is essential for the trans autophosphorylation of mtk1 at thr-1493 in the kinase activation loop.

SIGNOR-152408

P01106

Q9Y4D8

2

ubiquitination

down-regulates quantity by destabilization

0.2

We identified several E3 ligases as strong candidates responsible for AR and MYC protein loss as HECTD4, MYCBP2, and TRIM49. HECTD4 and MYCBP2 target AR and MYC for degradation while TRIM49 appears to promote AR and MYC stability. We have shown that these E3 ligases in turn are directly regulated by MYC. MYC in turn represses the expression of ubiquitin ligases, HECTD4 and MYCBP2 that promote AR and MYC protein degradation, further suppressing MYC and AR in a feed forward loop.

SIGNOR-267146

O43683

2

phosphorylation

up-regulates activity

0.2

Conversely, Bub1 is an active kinase regulated by intra-molecular phosphorylation at the P+1 loop.

SIGNOR-277186