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
Q96RG2	Q96RG2	2	phosphorylation	up-regulates activity	0.2	We present evidence that the activity of pask is regulated by two mechanisms. Autophosphorylation at two threonine residues located within the activation loop significantly increases catalytic activity.	SIGNOR-109481
P01024	P01024	2	cleavage	up-regulates activity	0.2	C3 autoactivates in a process known as “tick-over,” which is characterized by spontaneous hydrolysis of a reactive thiol-ester to generate C3(H2O). Although C3(H2O)Bb produces only relatively small amounts of C3b compared to the other C3 convertases, it nevertheless generates enough C3b to set the C3 convertase amplification loop in motion.	SIGNOR-263483
Q9ULU4	Q9ULU4	2	binding	up-regulates activity	0.2	We identified ZMYND8 as a transcriptional corepressor of the H3K4 demethylase JARID1D\|Co-immunoprecipitation between ectopically expressed FLAG-tagged JARID1D and endogenous ZMYND8 protein.	SIGNOR-262037
P06241	P06241	2	phosphorylation	up-regulates activity	0.2	Activated Fyn furthermore undergoes autophosphorylation on Tyr30, Tyr39 and Tyr420. Tyr28 This site is also a Fyn autophosphorylation site When Fyn mutants with Tyr28, Tyr30 or Tyr39 replaced with phenylalanine residues were transfected into NIH3T3 cells a decreased activation after PDGF stimulation was seen, suggesting a functional importance of the N-terminal tyrosine phosphorylation of Fyn.	SIGNOR-251167
Q05086	Q05086	2	ubiquitination	down-regulates quantity by destabilization	0.2	We show here that HPV16 E6 promotes the ubiquitination and degradation of E6AP itself.	SIGNOR-271398
P23771	P23771	2	null	up-regulates	0.2	Experimental data indeed supports the existence of a positive circuit involvingGATA-3 that excludes IL-4 and STAT-6, specifically in mouse cells	SIGNOR-254300
Q15139	Q15139	2	phosphorylation	up-regulates	0.2	Activation of the serine/threonine kinase, protein kinase d (pkd/pkc mu) via a phorbol ester/pkc-dependent pathway involves phosphorylation events. the second autophosphorylation site (ser(203)) lies in that region of the regulatory domain	SIGNOR-78676
O94972	O94972	2	polyubiquitination	down-regulates quantity by destabilization	0.2	In this paper, we present data showing that TRIM37, a member of the TRIM subfamily of RING finger proteins, is autoubiquitinated in a RING domain-dependent manner. However, we feel tempted to speculate that the most likely mechanism, in which TRIM37-mediated ubiquitination could be involved, is proteasomal degradation of a target protein and, possibly, its own turnover.	SIGNOR-271503
P11678	P11678	2	post translational modification	up-regulates activity	0.2	Human eosinophils are bone marrow-derived, non-dividing granulocytes of the innate immune system, which store the highly cationic proteins eosinophil peroxidase (EPO), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP) in secondary granules. we demonstrated that Tyr nitration of the eosinophil granule proteins is exclusively mediated by EPO, in the presence of functional NADPH oxidase and minute amounts of NOx. EPO appears to nitrate itself via an autocatalytic mechanism.	SIGNOR-261706
Q13164	Q13164	2	phosphorylation	up-regulates activity	0.2	Activated ERK5 undergoes autophosphorylation on its C-terminal half, necessary for maximal activation of ERK5 transcriptional activation. The Ser731 and Thr733 sites were previously shown to be ERK5 autophosphorylation sites in vitro and also in ERK5-overexpressing cells.Our data coincide with a recent study examining whole protein phosphorylation in HeLa cells arrested in G1 and mitotic phases [37] reported that Ser731 and Thr733, as well as Ser720, are phosphorylated in ERK5 during mitosis. We also identified two unreported ERK5 phosphorylation sites, Ser567 and Ser803.	SIGNOR-259826
Q09472	Q09472	2	acetylation	up-regulates activity	0.2	Brd3 interacts with both IRF3 and p300, increases p300-mediated acetylation of IRF3, and enhances the association of IRF3 with p300 upon virus infection.\|Brd3 enhances p300-mediated acetylation of IRF3\|Importantly, Brd3 promotes the recruitment of IRF3/p300 complex to the promoter of Ifnb1, and increases the acetylation of histone3/histone4 within the Ifnb1 promoter, leading to the enhancement of type I interferon production.	SIGNOR-262045
P53355	P53355	2	phosphorylation	down-regulates activity	0.2	The pro-apoptotic function of death-associated protein kinase is controlled by a unique inhibitory autophosphorylation-based mechanism.These results are consistent with a molecular model in which phosphorylation on ser(308) stabilizes a locked conformation of the cam-regulatory domain within the catalytic cleft and simultaneously also interferes with cam binding.	SIGNOR-110807
P05771	Q8NER1	2	binding	up-regulates activity	0.2	In the present study, we report that the sensitivity of TRPV1 channels is determined by PKCβII. TRPV1 binds directly to PKCβII and subsequently activates PKCβII. Activated PKCβII then enhances the responsiveness of TRPV1 to thermal and chemical stimuli through a phosphorylation-dependent mechanism.	SIGNOR-276639
P42345	P42345	2	phosphorylation	up-regulates activity	0.2	We have found that in HEK293 cells and 3T3-L1 adipocytes, insulin promotes both raptor- and rictor-associated mTOR Ser(P)-2481 in a wortmannin-sensitive manner. Thus, insulin signals via PI3K to promote both mTORC1- and mTORC2-associated mTOR Ser-2481 autophosphorylation.	SIGNOR-235427
Q96GD4	Q96GD4	2	phosphorylation	up-regulates	0.2	We report here that human aurora-b is phosphorylated at thr-232 through interaction with the inner centromere protein (incenp) in vivo. The phosphorylation of thr-232 occurs by means of an autophosphorylation mechanism, which is indispensable for the aurora-b kinase activity.	SIGNOR-121340
P84022	P84022	2	binding	up-regulates activity	0.2	Smad2 and Smad3 form homo-oligomers upon phosphorylation by the constitutively active TGF-beta type I receptor, and this oligomerization does not require Smad4	SIGNOR-217227
Q15569	Q15569	2	phosphorylation	up-regulates activity	0.2	Site-directed mutagenesis analyses revealed that Ser-215 within the activation loop of the kinase domain is the site of serine autophosphorylation of TESK1. Replacement of Ser-215 by alanine almost completely abolished serine autophosphorylation and histone H3 kinase activities.	SIGNOR-246667
P18850	P18850	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-224202
Q13043	Q13043	2	phosphorylation	up-regulates activity	0.2	Mapping of MST1 kinase sites of phosphorylation. Activation and autophosphorylationWe define Thr(183) in subdomain VIII as a primary site of phosphoactivation. Thr(187) is also critical for kinase activity.	SIGNOR-247581
Q15835	Q15835	2	phosphorylation	down-regulates activity	0.2	The major autophosphorylation site yielded the following sequence: DVGAFS488T489VKGVAFEK, where Ser488 and Thr489 are phosphorylated. Additionally, a minor autophosphorylation site was identified at Ser21. we speculate that autophosphorylation of RK may lower the affinity of the enzyme for Rho* via repulsion between phosphorylated sites on Rho* and the kinase.	SIGNOR-251187
O15409	O15409	2	binding	up-regulates activity	0.2	Our studies also reveal that the FOXP2 forkhead domain can form a domain-swapped dimer. The most surprising finding from these studies is that the FOXP2 forkhead domain can form a domain-swapped dimer. Disease-related mutations, sequence comparison, and biochemical analyses argue strongly that this domain swapping is a physiologically relevant function evolved in the P branch of FOX proteins.	SIGNOR-225738
Q9BVG3	Q9BVG3	2	polyubiquitination	down-regulates quantity by destabilization	0.2	A ubiquitination assay performed in HEK293T cells further confirmed the E3 ubiquitin ligase activity and self-ubiquitination activity of TRIM62 and the requirement of the RING finger domain. Importantly, the treatment of HEK293T cells with a proteasome inhibitor stabilized poly-ubiquitinated TRIM62, indicating that self-ubiquitination promoted the proteasomal degradation of TRIM62.	SIGNOR-272102
Q16512	Q16512	2	phosphorylation	up-regulates activity	0.2	Autophosphorylation of wild-type PKN increased the protein kinase activity, however, substitution of Thr64, Ser374, or Thr531 in the regulatory region of PKN with alanine, abolished this effect.	SIGNOR-249020
Q13315	Q13315	2	phosphorylation	up-regulates activity	0.2	In human cells, the activation process involves autophosphorylation on three sites (ser367, ser1893, and ser1981) and acetylation on lys3016. We now describe the identification of a new atm phosphorylation site, thr(p)1885 and an additional autophosphorylation site, ser(p)2996, that is highly dna damage-inducible.	SIGNOR-170477
Q13418	Q13418	2	phosphorylation	up-regulates activity	0.2	Although ilk has been shown to autophosphorylate serine 343 (s343) is in the hydrophobic motif fsf within the activation loop of the kinase domain and has previously been suggested to be the target of autophosphorylation (9). Mutation of serine 343 to alanine (s343a) resulted in the inability of ilk to stimulate phosphorylation of pkb/akt in cos cells (9).	SIGNOR-106838
O14965	O14965	2	phosphorylation	up-regulates	0.2	The upstream pak1 kinase can phosphorylate aurora a at t288, autophosphorylation appears to be the essential mode of activation. Our experiments suggest that phosphorylation of t288 is important for regulation of the aurora2 kinase both for its activity and its stability	SIGNOR-205106
Q16584	Q16584	2	phosphorylation	up-regulates	0.2	These residues within the activation loop are critical for mlk-3 autophosphorylation and activation. In addition, when the thr277 and ser281 residues were mutated to negatively charged glutamic acid to mimic phosphorylated serine/threonine residues, the resulting mutants were fully functional, implying that these two residues may serve as the autophosphorylation sites.	SIGNOR-83407
Q8TD08	Q8TD08	2	phosphorylation	up-regulates	0.2	Erk8 (extracellular-signal-regulated protein kinase 8) expressed in escherichia coli or insect cells was catalytically active and phosphorylated at both residues of the thr-glu-tyr motif.Our results suggest that the activity of erk8 in transfected hek-293 cells depends on the relative rates of erk8 autophosphorylation	SIGNOR-142969
P42684	P42684	2	phosphorylation	up-regulates quantity by stabilization	0.2	The results show that Arg is stabilized in response to 0.1 mM H2O2 by autophosphorylation of Y-261, consistent with involvement of the Arg kinase function in regulating Arg levels. The results further demonstrate that c-Abl-mediated phosphorylation of Arg on Y-261 similarly confers Arg stabilization.. These findings indicate that abrogation of the Arg kinase function by the Y261F mutation is dependent on phosphorylation of the Y-439 site.	SIGNOR-276033
Q9Y2H1	Q9Y2H1	2	phosphorylation	up-regulates	0.2	Ndr1/ndr2 protein kinase is activated by phosphorylation on the activation loop phosphorylation site ser281/ser282 and the hydrophobic motif phosphorylation site thr444/thr442. Autophosphorylation of ndr is responsible for phosphorylation on ser281/ser282, whereas thr444/thr442 is targeted by an upstream kinase. Here we show that mst3, a mammalian ste20-like protein kinase, is able to phosphorylate ndr protein kinase at thr444/thr442. In vitro, mst3 selectively phosphorylated thr442 of ndr2, resulting in a 10-fold stimulation of ndr activity.	SIGNOR-142518
Q9Y463	Q9Y463	2	phosphorylation	up-regulates	0.2	Mirk kinase is activated by autophosphorylation on tyrosine at the y271/y273 site	SIGNOR-79810
P04629	P04629	2	phosphorylation	up-regulates	0.2	In vitro studies indicate that trka autophosphorylates at tyrosines 490, 670, 674, 675, and 785	SIGNOR-47171
P16234	P16234	2	phosphorylation	up-regulates activity	0.2	We have identified two autophosphorylation sites, Tyr-988 and Tyr-1018, in the platelet-derived growth factor (PDGF) alpha-receptor carboxyl-terminal tail, which are involved in binding of phospholipase C-gamma (PLC-gamma). We conclude that phosphorylated Tyr-988 and Tyr-1018 in the PDGF α-receptor carboxyl-terminal tail bind PLC-γ, but this association leads to only a relatively low level of tyrosine phosphorylation and activation of PLC-γ.	SIGNOR-250252
Q9UIK4	Q9UIK4	2	phosphorylation	down-regulates activity	0.2	Autophosphorylation restrains the apoptotic activity of DRP-1 kinase by controlling dimerization and calmodulin binding. \| It comprises a single autophosphorylation event mapped to Ser308 within the CaM regulatory domain.	SIGNOR-251084
Q96BA8	Q96BA8	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-224205
P22455	P22455	2	phosphorylation	up-regulates	0.2	Binding of fgf to fgf receptors leads to receptor dimerization and subsequent tyrosine autophosphorylation and phosphorylation of target substrates. Autophosphorylation on tyrosine is considered to have at least two functions. One such function is the stimulation of the intrinsic protein tyrosine kinase activity by an allosteric mechanismthis antibody specifically recognizes tyr642/643 in fgfr-4.	SIGNOR-179776
Q9H2K8	Q9H2K8	2	phosphorylation	up-regulates activity	0.2	These data indicate that JIK is indeed the protein kinase present in the immune complex responsible for autophosphorylation and for the phosphorylation of the exogenous substrate. Moreover, our observations suggest that JIK (A181F183) acts as the catalytically inactive mutant of JIK, which is no longer able to potently undergo autophosphorylation and dramatically phosphorylate MBP, as compared with the wild type JIK.	SIGNOR-246302
Q5VT25	Q5VT25	2	phosphorylation	up-regulates activity	0.2	N terminus-mediated dimerization and transautophosphorylation are essential for MRCKα catalytic activity. Three mutations, S234A, T240A, and T403A, strongly affected the in vitro autophosphorylation activity of FLAG-MRCKα-CAT1–473 (Fig. (Fig.5D).5D).	SIGNOR-275974
O00329	O00329	2	phosphorylation	down-regulates	0.2	Autophosphorylation of p110delta phosphoinositide 3-kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo in vitro autophosphorylation of p110delta completely down-regulates its lipid kinase activity.	SIGNOR-65186
P42681	P42681	2	phosphorylation	up-regulates	0.2	Evidence of autophosphorylation in txk: y91 is an autophosphorylation site. the results suggest that phosphorylated txk is an active form to promote ifn-gamma synthesis	SIGNOR-89844
Q9NR20	Q9NR20	2	phosphorylation	up-regulates activity	0.2	Autophosphorylation of DYRK4 in the Activation Loop Is Required for Kinase Activity	SIGNOR-260827
P29320	P29320	2	phosphorylation	up-regulates activity	0.2	Eph receptor activation leads to tyrosine phosphorylation of three major autophosphorylation sites. these residues function to regulate kinase activity, their phosphorylation being required for full intrinsic enzyme activity. these tyrosines (EphA3 Y596, Y602 and Y779) as the prominent autophosphorylation sites of EphA3	SIGNOR-251115
P22392	P22392	2	phosphorylation	up-regulates activity	0.2	Using site-directed mutagenesis of the cDNA encoding NM23-H2, we have created a mutant substituting for the amino acid histidine 118, the presumed site of phosphorylation in the formation of the phosphoenzyme intermediate, the nonphosphorylatable amino acid phenylalanine. The H118F mutant protein is shown to be catalytically inactive	SIGNOR-250304
Q99558	Q99558	2	phosphorylation	up-regulates activity	0.2	As nik levels increase, nik presumably becomes activated by autophosphorylation (p).	SIGNOR-167063
Q16665	Q9H3R0	2	binding	up-regulates activity	0.2	In hypoxia, HIF-1α dimerizes with HIF-1β to form active HIF-1 complex. JMJD2C interacts with HIF-1α and promotes the transcriptional activation of HIF-1 targeting genes via demethylating di- and trimethylated H3K9.	SIGNOR-263873
O00635	O00635	2	polyubiquitination	down-regulates quantity by destabilization	0.2	Our study shows that, similar to other TRIM family members, TRIM38 is localized in the cytoplasm. TRIM38 increases ubiquitination of other cellular proteins and catalyzes self-ubiquitination. TRIM38 also promotes K63- and K48-linked ubiquitination of cellular proteins. An intact RING domain is important for the functions of TRIM38. In addition, enterovirus 71 infection induces TRIM38 degradation.	SIGNOR-271906
P49760	P49760	2	phosphorylation	up-regulates	0.2	Clk2 was reported to regulate its nuclear localization by autophosphorylating serine 141	SIGNOR-167344
P15531	P15531	2	phosphorylation	up-regulates activity	0.2	An acid-stable (nonhistidine) phosphorylation was identified on autophosphorylated purified recombinant Nm23 proteins and [32P]orthophosphate-labeled human breast carcinoma and murine melanoma Nm23. Phosphoamino acid analysis identified serine as the acid-stable phosphorylation and serine 44 as the major site of phosphorylation. The biological relevance of the novel phosphorylation identified herein is suggested by the direct correlation of in vivo Nm23 acid-stable phosphorylation levels, but not Nm23 NDPK activity, with suppression of tumor metastatic potential among control and nm23-1 transfected murine melanoma cells.	SIGNOR-250303
Q9UMX1	Q9UMX1	2	binding	up-regulates	0.2	Hsu(fu) associated with itself / homo- or heterodimers of hsu(fu) might function to bring together other effector proteins	SIGNOR-72311
Q9BXA7	Q9BXA7	2	phosphorylation	up-regulates activity	0.2	Electrospray Q‐TOF2 mass spectroscopy analysis of a trypsin digested TSSK1 purified from E. coli, revealed that it was phosphorylated at its T‐loop residue (Fig. 2D), indicating that TSSK1 as was previously shown for MELK [18], can autophosphorylate its T‐loop Thr residue.	SIGNOR-260823
O96013	O96013	2	phosphorylation	up-regulates	0.2	Intracellular localization;enzymatic activity, induced;cell growth, altered;	SIGNOR-168301
Q13330	Q8NHY2	2	polyubiquitination	down-regulates quantity by destabilization	0.2	Here we report that MTA1 is an ubiquitinated protein and targeted by the RING-finger E3 ubiquitin-protein ligase constitutive photomorphogenesis protein 1 (COP1) for degradation via the ubiquitin-proteasome pathway.	SIGNOR-271891
P21802	P21802	2	phosphorylation	up-regulates activity	0.2	Our data also show that tyrosine 769 is not involved in the regulation of the endocytic process of KGFR.Following ligand binding, KGFR is rapidly autophosphorylated on specific tyrosine residues	SIGNOR-276026
Q05655	Q05655	2	phosphorylation	up-regulates	0.2	This study identifies novel in vitro pkcdelta autophosphorylation sites at thr(141) adjacent to the pseudosubstrate domain, thr(218) in the c1a-c1b interdomain, ser(295), ser(302), and ser(304) in the hinge region, and ser(503) adjacent to thr(505) in the activation loop. studies reported herein show that a t505a substitution reduces pkcdelta-thr(295) autophosphorylation	SIGNOR-185287
Q9UK32	Q9UK32	2	phosphorylation	up-regulates activity	0.2	These mutants had minimal kinase activity and showed profoundly decreased phosphorylation at Ser232 compared with wild-type RSK4 (Fig 10B), suggesting that RSK4 can autophosphorylate at Ser232.	SIGNOR-275797
P00558	O15530	2	phosphorylation	up-regulates activity	0.2	PDPK1 Phosphorylates PGK1 T243. Macrophages increase PGK1 pT243 to reduce the 3-PG affinity of PGK1, which alters the equilibrium of the PGK1-catalyzed reaction toward glycolysis, promoting tumor cell proliferation.	SIGNOR-277402
P52564	P52564	2	phosphorylation	up-regulates activity	0.2	However, the autocatalytic activities of both mkk6 and mkk7 were enhanced by their coexpression with either mekk3 or mekk2.	SIGNOR-236122
Q92630	P30304	2	dephosphorylation	down-regulates activity	0.2	Finally, DYRK2 is dephosphorylated by CDC25A, suggesting a feedback regulatory loop.\|Notably, the co-expression of CDC25A inhibited the DYRK2 pro-apoptotic effect (Fig.\u00a06D), concurring with a possible inhibitory role on DYRK2 activity and further suggesting that the effect of DYRK2 was dependent on CDC25A.	SIGNOR-277098
Q99759	Q99759	2	phosphorylation	up-regulates	0.2	Phosphorylation of serine 526 is required for mekk3 activity, and association with 14-3-3 blocks dephosphorylationautophosphorylation of mekk3 at ser526	SIGNOR-143647
Q9Y4D8	P01106	2	transcriptional regulation	down-regulates quantity by repression	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-267144
Q13976	Q13976	2	phosphorylation	up-regulates	0.2	Serines 64 and 79 are homologous residues that are juxtaposed to the autoinhibitory pseudosubstrate site in cgmp-dependent protein kinase type ialpha and type ibeta (pkg-ialpha and pkg-ibeta), respectively. Autophosphorylation of this residue is associated with activation of type i pkgs.	SIGNOR-89839
P31323	P31323	2	phosphorylation	up-regulates activity	0.2	Ser114 (the autophosphorylation site) of human RII beta. Point mutation of the autophosphorylation site or in the nuclear location signal causes protein kinase A RII beta regulatory subunit to lose its ability to revert transformed fibroblasts.	SIGNOR-250076
Q9UHD2	Q86WV6	2	binding	up-regulates activity	0.2	MAVS also interacts with STING that locates at the ER (endoplasmic reticulum), and induces the ubiquitination and dimerization of STING. The activated STING recruits TBK1 and IRF3 and contributes to the phosphorylation of IRF3 mediated by TBK1.	SIGNOR-260153
Q9Y6E0	Q9Y6E0	2	phosphorylation	up-regulates	0.2	Inhibition of cell migration by autophosphorylated mammalian sterile 20-like kinase 3 (mst3) involves paxillin and protein-tyrosine phosphatase-pest.	SIGNOR-150131
Q9H0K1	Q9H0K1	2	phosphorylation	up-regulates activity	0.2	SIK2 S358 Autophosphorylation Is a Marker of SIK2 Activity	SIGNOR-277268
P34947	P34947	2	phosphorylation	up-regulates activity	0.2	Autophosphorylation of GRK5 occurs primarily at residues Ser-484 and Thr-485. Phospholipid-stimulated autophosphorylation activates the G protein-coupled receptor kinase GRK5.	SIGNOR-251201
O75460	O75460	2	phosphorylation	up-regulates activity	0.2	IRE1 transduces the unfolded protein response by splicing XBP1 through its C-terminal cytoplasmic kinase-RNase region. IRE1 autophosphorylation is coupled to RNase activity through formation of a back-to-back dimer, although the conservation of the underlying molecular mechanism is not clear from existing structures.	SIGNOR-275417
P18433	P18433	2	dephosphorylation	down-regulates activity	0.2	Transient overexpression of c-Src together with RPTP alpha in human embryonic kidney 293 cells increased phosphorylation of Tyr789, suggesting that c-Src may phosphorylate RPTP alpha in vivo. RPTP alpha had autodephosphorylation activity in vitro. When expressed in 293 cells the level of Tyr789 phosphorylation was higher in a non-functional mutant of RPTP alpha than in wild type RPTP alpha, indicating that RPTP alpha may have autodephosphorylation activity in vivo as well.\|We show that RPTP alpha, but not a mutant of RPTP alpha with a Tyr-->Phe mutation at position 789, bound to GRB2 in vitro.	SIGNOR-248439
P12931	P12931	2	phosphorylation	down-regulates activity	0.2	Rapid digestion of pp60c-src tyrosine kinase (src TK) in combination with electrospray ionization mass spectrometry enabled the determination of the time course for autophosphorylation of three tyrosine sites (Y338, Y419, and Y530) and a correlation with src TK activity. Here, conditions were identified which promoted essentially complete autophosphorylation of y530. Phosphorylation of y530 was directly correlated to a decrease in tyrosine kinase activity	SIGNOR-43315
Q9BYT3	Q9BYT3	2	phosphorylation	up-regulates activity	0.2	Our results show that the serine/threonine kinase Stk33 phosphorylates the intermediate filament protein vimentin in vitro specifically in the vimentin head domain. Stk33 undergoes obligatory autophosphorylation, which might be a prerequisite for its kinasing activity.	SIGNOR-272957
Q13490	Q13490	2	ubiquitination	down-regulates quantity by destabilization	0.2	Ciap1 and ciap2 undergo autoubiquitination and degradation upon binding to the iap antagonist second mitochondrial activator of caspases (smac)/direct iap-binding protein with low pi (diablo), which is released from the mitochondria.	SIGNOR-121877
O14641	O14641	2	binding	up-regulates activity	0.2	Dix domain of dvl2 mediates dynamic polymerization, which is essential for the signaling activity of dvl2.	SIGNOR-155224
Q96PN8	Q96PN8	2	phosphorylation	up-regulates activity	0.2	We elucidated the mechanism of regulation of TSSK3 activity showing that autophosphorylation and PDK1 phosphorylation in the ‘activation loop’ are necessary for activation.	SIGNOR-260785
P42224	P42224	2	binding	up-regulates activity	0.2	Each STAT1 monomer becomes tyrosine phosphorylated at tyrosine 701 by the JAKs, dissociates from the receptor to form a STAT1-STAT1 homodimer which translocates to the nucleus	SIGNOR-249495
Q16236	O00625	2	binding	up-regulates activity	0.2	In contrast, the depletion of PIR initiates HMGB1-dependent autophagy by binding to BECN1, and subsequently promotes ferroptosis by activating ACSL4.	SIGNOR-279852
Q13315	P49959	2	binding	up-regulates	0.2	One of the earliest events is recruitment and activation of the atm at the damaged dna sites through the mre11rad50nbs1 (mrn) sensor complex. the mre11/rad50/nbs1 (mrn) complex maintains genomic stability by bridging dna ends and initiating dna damage signaling through activation of the atm kinase.	SIGNOR-175006
O43379	Q99759	2	binding	up-regulates quantity by stabilization	0.2	Specifically, we demonstrate that MEKK3 interacts with WDR62 to stabilize WDR62 and regulates JNK activity in a synergic way. On the other hand, JNK activity also regulates the phosphorylation of WDR62 at T1053 in a feedback loop which facilities the recruitment of FBW7 degradation of WDR62	SIGNOR-271714
Q8TF76	P53350	2	phosphorylation	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-275421
P40189	P40189	2	phosphorylation	up-regulates activity	0.2	The biological functions of interleukin-6 (IL-6) are mediated through a signal-transducing component of the IL-6 receptor, gp130, which is associated with the ligand-occupied IL-6 receptor (IL-6R) protein. Binding of IL-6 to IL-6R induced disulfide-linked homodimerization of gp130. Tyrosine kinase activity was associated with dimerized but not monomeric gp130 protein. Substitution of serine for proline residues 656 and 658 in the cytoplasmic motif abolished tyrosine kinase activation and cellular responses but not homodimerization of gp130.	SIGNOR-238625
Q16659	Q16659	2	phosphorylation	up-regulates	0.2	Ser189 of erk3, which corresponds to thr183, one of the activating phosphorylation sites of erk2, is autophosphorylated in vitro and phosphorylated in vivo.	SIGNOR-40097
P29323	P29323	2	phosphorylation	up-regulates activity	0.2	Our results demonstrate that autophosphorylation tyrosine 611 in the juxtamembrane region of chicken EphB2 is critical for the association of the Src SH2 domain.	SIGNOR-251124
Q96J92	Q96J92	2	phosphorylation	down-regulates activity	0.2	Elimination of the catalytic activity (D321A or D321K-K186D) or the autophosphorylation site (S335A) in mutant WNK4-L322F abrogated the positive effect on NCC.	SIGNOR-276871
Q7Z569	Q7Z569	2	ubiquitination	down-regulates quantity by destabilization	0.2	Here we report on a novel interaction between the E3 ligase BRAP (also referred to as IMP), a negative regulator of the MAPK scaffold protein KSR, and two closely related deubiquitylases, USP15 and USP4. USP15 as well as USP4 oppose the autoubiquitylation of BRAP, whereas BRAP promotes the ubiquitylation of USP15.	SIGNOR-272027
Q86WV6	Q9UHD2	2	phosphorylation	up-regulates activity	0.2	MITA was phosphorylated by TBK1, which is required for MITA-mediated activation of IRF3. Our results suggest that MITA is a critical mediator of virus-triggered IRF3 activation and IFN expression and further demonstrate the importance of certain mitochondrial proteins in innate antiviral immunity. Consistent with its inability to activate IRF-E, the mutation of S358 to alanine impaired the ability of MITA to interact with TBK1 and to enhance the interaction between TBK1 and IRF3	SIGNOR-263136
Q13470	Q13470	2	phosphorylation	up-regulates activity	0.2	We found a similar reduction in the levels of phosphorylation of Tyr277, which corresponds to the predicted major site of autophosphorylation within the activation loop of Tnk1 (Fig. 3C).	SIGNOR-274126
P09619	P25098	2	phosphorylation	down-regulates activity	0.2	In 293 cells, GRK2 overexpression reduced PDGFRbeta/NHERF association by 60%.	SIGNOR-278379
Q9BZL6	Q9BZL6	2	phosphorylation	up-regulates	0.2	The addition of phorbol 12,13-dibutyrate in the presence of dioleoylphosphatidylserine stimulated the autophosphorylation of pkd2 in a synergistic fashion.In addition, we could identify the c-terminal ser(876) residue as an in vivo phosphorylation site within pkd2. Phosphorylation of ser(876) of pkd2 correlated with the activation status of the kinase.	SIGNOR-83834
P23470	P23470	2	binding	down-regulates activity	0.2	The main regulatory mechanism of RPTP activity consists of the reversible transition from a homodimeric inactive form to a monomeric active form. PTPRG is constitutively expressed on monocyte plasma membrane as a homodimer with the WD involved in catalytic domain blockade.	SIGNOR-254737
O75914	O75914	2	phosphorylation	up-regulates activity	0.2	Both in vivo and in vitro analyses demonstrate that, although most phosphorylation events in the PAK N-terminal regulatory domain play no direct role in activation, a phosphorylation of alphaPAK serine 144 or betaPAK serine 139, which lie in the kinase inhibitory domain, significantly contribute to activation.	SIGNOR-250245
P20794	P20794	2	phosphorylation	up-regulates activity	0.2	We conclude that dual phosphorylation on the TDY motif is crucial for MAK activity, and that the autokinase activity is required for this phosphorylation	SIGNOR-260779
P29322	P29322	2	phosphorylation	up-regulates activity	0.2	Tyr-615 and Tyr-838 are major autophosphorylation sites of the EphA8 receptor. phosphorylation of Tyr-615 is critical for determining the association with Fyn whereas the integrity of Tyr-838 phosphorylation is required for efficient phosphorylation at Tyr-615 as well as other major sites.	SIGNOR-251121
Q9H3R0	Q16665	2	transcriptional regulation	up-regulates quantity by expression	0.2	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271570
P17612	Q02952	2	relocalization	up-regulates activity	0.2	A-kinase-anchoring protein 250 (AKAP250; gravin) acts as a scaffold that binds protein kinase A (PKA), protein kinase C and protein phosphatases, associating reversibly with the beta(2)-adrenergic receptor.	SIGNOR-271835
P49841	P49841	2	phosphorylation	up-regulates activity	0.2	Phosphorylation of the residue Tyrosine in 216 position results in the constitutive activity of GSK-3beta and believed to be important target for signal transduction.	SIGNOR-217865
O00418	O00418	2	phosphorylation	down-regulates	0.2	The combination of eef2k autophosphorylation (targeting ser445) and a yet to be identified kinase (targeting ser441) would be needed to generate the eef2k phosphodegron specifically in response to dna damage.	SIGNOR-197725
Q15796	Q15796	2	binding	up-regulates activity	0.2	Smad2 and Smad3 form homo-oligomers upon phosphorylation by the constitutively active TGF-beta type I receptor, and this oligomerization does not require Smad4	SIGNOR-232149
P12644	P12644	2	binding	up-regulates	0.2	Bmps are dimeric proteins with a single inter-chain disulfide bond. The dimeric conformation is anabsolute requirement for the biological action and interaction with receptors	SIGNOR-236169
P09769	P09769	2	phosphorylation	up-regulates activity	0.2	Autophosphorylation of c-Fgr under basal conditions involves Tyr-400 (homologous of c-Src Tyr-416) but not, to any appreciable extent, Tyr-511. Both Tyr-511 and Tyr-400, however, incorporate phosphate if autophosphorylation is performed in the presence of polycationic peptides, such as polylysine, histones H1 and protamines. Such a double phosphorylation induced by polylysine gives rise to an upshifted form of c-Fgr on SDS-PAGE and correlates with a stimulation of catalytic activity instead of a down-regulation	SIGNOR-251143
P17252	P17252	2	phosphorylation	up-regulates	0.2	Pkc is frequently autophosphorylated on two c-terminal sites, the turn motif (thr- 638 in human pkc) and the hydrophobic site (ser-657 in human pkc). Thus, it is becoming clear that autophosphorylation of pkc can be a regulated event and that it has significant impact on pkc function	SIGNOR-127253
O75676	O75676	2	phosphorylation	up-regulates activity	0.2	Here we report that the CK2 protein kinase, which contributes to NF-kappaB activation following UV radiation in a p38-dependent manner, physically interacts with MSK2 but not MSK1 and that CK2 inhibition specifically impairs UV-induced MSK2 kinase activation. A putative site of CK2 phosphorylation was mapped to MSK2 residue Ser(324) and when substituted to alanine (S324A) also compromised MSK2 activity.Serine 324 is required for UV-induced MSK2 activation and for autophosphorylation at MSK2-Ser196.	SIGNOR-276269

Q96RG2

2

phosphorylation

up-regulates activity

0.2

We present evidence that the activity of pask is regulated by two mechanisms. Autophosphorylation at two threonine residues located within the activation loop significantly increases catalytic activity.

SIGNOR-109481

P01024

2

cleavage

up-regulates activity

0.2

C3 autoactivates in a process known as “tick-over,” which is characterized by spontaneous hydrolysis of a reactive thiol-ester to generate C3(H2O). Although C3(H2O)Bb produces only relatively small amounts of C3b compared to the other C3 convertases, it nevertheless generates enough C3b to set the C3 convertase amplification loop in motion.

SIGNOR-263483

Q9ULU4

2

binding

up-regulates activity

0.2

We identified ZMYND8 as a transcriptional corepressor of the H3K4 demethylase JARID1D|Co-immunoprecipitation between ectopically expressed FLAG-tagged JARID1D and endogenous ZMYND8 protein.

SIGNOR-262037

P06241

2

phosphorylation

up-regulates activity

0.2

Activated Fyn furthermore undergoes autophosphorylation on Tyr30, Tyr39 and Tyr420. Tyr28 This site is also a Fyn autophosphorylation site When Fyn mutants with Tyr28, Tyr30 or Tyr39 replaced with phenylalanine residues were transfected into NIH3T3 cells a decreased activation after PDGF stimulation was seen, suggesting a functional importance of the N-terminal tyrosine phosphorylation of Fyn.

SIGNOR-251167

Q05086

2

ubiquitination

down-regulates quantity by destabilization

0.2

We show here that HPV16 E6 promotes the ubiquitination and degradation of E6AP itself.

SIGNOR-271398

P23771

2

null

up-regulates

0.2

Experimental data indeed supports the existence of a positive circuit involvingGATA-3 that excludes IL-4 and STAT-6, specifically in mouse cells

SIGNOR-254300

Q15139

2

phosphorylation

up-regulates

0.2

Activation of the serine/threonine kinase, protein kinase d (pkd/pkc mu) via a phorbol ester/pkc-dependent pathway involves phosphorylation events. the second autophosphorylation site (ser(203)) lies in that region of the regulatory domain

SIGNOR-78676

O94972

2

polyubiquitination

down-regulates quantity by destabilization

0.2

In this paper, we present data showing that TRIM37, a member of the TRIM subfamily of RING finger proteins, is autoubiquitinated in a RING domain-dependent manner. However, we feel tempted to speculate that the most likely mechanism, in which TRIM37-mediated ubiquitination could be involved, is proteasomal degradation of a target protein and, possibly, its own turnover.

SIGNOR-271503

P11678

2

post translational modification

up-regulates activity

0.2

Human eosinophils are bone marrow-derived, non-dividing granulocytes of the innate immune system, which store the highly cationic proteins eosinophil peroxidase (EPO), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP) in secondary granules. we demonstrated that Tyr nitration of the eosinophil granule proteins is exclusively mediated by EPO, in the presence of functional NADPH oxidase and minute amounts of NOx. EPO appears to nitrate itself via an autocatalytic mechanism.

SIGNOR-261706

Q13164

2

phosphorylation

up-regulates activity

0.2

Activated ERK5 undergoes autophosphorylation on its C-terminal half, necessary for maximal activation of ERK5 transcriptional activation. The Ser731 and Thr733 sites were previously shown to be ERK5 autophosphorylation sites in vitro and also in ERK5-overexpressing cells.Our data coincide with a recent study examining whole protein phosphorylation in HeLa cells arrested in G1 and mitotic phases [37] reported that Ser731 and Thr733, as well as Ser720, are phosphorylated in ERK5 during mitosis. We also identified two unreported ERK5 phosphorylation sites, Ser567 and Ser803.

SIGNOR-259826

Q09472

2

acetylation

up-regulates activity

0.2

Brd3 interacts with both IRF3 and p300, increases p300-mediated acetylation of IRF3, and enhances the association of IRF3 with p300 upon virus infection.|Brd3 enhances p300-mediated acetylation of IRF3|Importantly, Brd3 promotes the recruitment of IRF3/p300 complex to the promoter of Ifnb1, and increases the acetylation of histone3/histone4 within the Ifnb1 promoter, leading to the enhancement of type I interferon production.

SIGNOR-262045

P53355

2

phosphorylation

down-regulates activity

0.2

The pro-apoptotic function of death-associated protein kinase is controlled by a unique inhibitory autophosphorylation-based mechanism.These results are consistent with a molecular model in which phosphorylation on ser(308) stabilizes a locked conformation of the cam-regulatory domain within the catalytic cleft and simultaneously also interferes with cam binding.

SIGNOR-110807

P05771

Q8NER1

2

binding

up-regulates activity

0.2

In the present study, we report that the sensitivity of TRPV1 channels is determined by PKCβII. TRPV1 binds directly to PKCβII and subsequently activates PKCβII. Activated PKCβII then enhances the responsiveness of TRPV1 to thermal and chemical stimuli through a phosphorylation-dependent mechanism.

SIGNOR-276639

P42345

2

phosphorylation

up-regulates activity

0.2

We have found that in HEK293 cells and 3T3-L1 adipocytes, insulin promotes both raptor- and rictor-associated mTOR Ser(P)-2481 in a wortmannin-sensitive manner. Thus, insulin signals via PI3K to promote both mTORC1- and mTORC2-associated mTOR Ser-2481 autophosphorylation.

SIGNOR-235427

Q96GD4

2

phosphorylation

up-regulates

0.2

We report here that human aurora-b is phosphorylated at thr-232 through interaction with the inner centromere protein (incenp) in vivo. The phosphorylation of thr-232 occurs by means of an autophosphorylation mechanism, which is indispensable for the aurora-b kinase activity.

SIGNOR-121340

P84022

2

binding

up-regulates activity

0.2

Smad2 and Smad3 form homo-oligomers upon phosphorylation by the constitutively active TGF-beta type I receptor, and this oligomerization does not require Smad4

SIGNOR-217227

Q15569

2

phosphorylation

up-regulates activity

0.2

Site-directed mutagenesis analyses revealed that Ser-215 within the activation loop of the kinase domain is the site of serine autophosphorylation of TESK1. Replacement of Ser-215 by alanine almost completely abolished serine autophosphorylation and histone H3 kinase activities.

SIGNOR-246667

P18850

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-224202

Q13043

2

phosphorylation

up-regulates activity

0.2

Mapping of MST1 kinase sites of phosphorylation. Activation and autophosphorylationWe define Thr(183) in subdomain VIII as a primary site of phosphoactivation. Thr(187) is also critical for kinase activity.

SIGNOR-247581

Q15835

2

phosphorylation

down-regulates activity

0.2

The major autophosphorylation site yielded the following sequence: DVGAFS488T489VKGVAFEK, where Ser488 and Thr489 are phosphorylated. Additionally, a minor autophosphorylation site was identified at Ser21. we speculate that autophosphorylation of RK may lower the affinity of the enzyme for Rho* via repulsion between phosphorylated sites on Rho* and the kinase.

SIGNOR-251187

O15409

2

binding

up-regulates activity

0.2

Our studies also reveal that the FOXP2 forkhead domain can form a domain-swapped dimer. The most surprising finding from these studies is that the FOXP2 forkhead domain can form a domain-swapped dimer. Disease-related mutations, sequence comparison, and biochemical analyses argue strongly that this domain swapping is a physiologically relevant function evolved in the P branch of FOX proteins.

SIGNOR-225738

Q9BVG3

2

polyubiquitination

down-regulates quantity by destabilization

0.2

A ubiquitination assay performed in HEK293T cells further confirmed the E3 ubiquitin ligase activity and self-ubiquitination activity of TRIM62 and the requirement of the RING finger domain. Importantly, the treatment of HEK293T cells with a proteasome inhibitor stabilized poly-ubiquitinated TRIM62, indicating that self-ubiquitination promoted the proteasomal degradation of TRIM62.

SIGNOR-272102

Q16512

2

phosphorylation

up-regulates activity

0.2

Autophosphorylation of wild-type PKN increased the protein kinase activity, however, substitution of Thr64, Ser374, or Thr531 in the regulatory region of PKN with alanine, abolished this effect.

SIGNOR-249020

Q13315

2

phosphorylation

up-regulates activity

0.2

In human cells, the activation process involves autophosphorylation on three sites (ser367, ser1893, and ser1981) and acetylation on lys3016. We now describe the identification of a new atm phosphorylation site, thr(p)1885 and an additional autophosphorylation site, ser(p)2996, that is highly dna damage-inducible.

SIGNOR-170477

Q13418

2

phosphorylation

up-regulates activity

0.2

Although ilk has been shown to autophosphorylate serine 343 (s343) is in the hydrophobic motif fsf within the activation loop of the kinase domain and has previously been suggested to be the target of autophosphorylation (9). Mutation of serine 343 to alanine (s343a) resulted in the inability of ilk to stimulate phosphorylation of pkb/akt in cos cells (9).

SIGNOR-106838

O14965

2

phosphorylation

up-regulates

0.2

The upstream pak1 kinase can phosphorylate aurora a at t288, autophosphorylation appears to be the essential mode of activation. Our experiments suggest that phosphorylation of t288 is important for regulation of the aurora2 kinase both for its activity and its stability

SIGNOR-205106

Q16584

2

phosphorylation

up-regulates

0.2

These residues within the activation loop are critical for mlk-3 autophosphorylation and activation. In addition, when the thr277 and ser281 residues were mutated to negatively charged glutamic acid to mimic phosphorylated serine/threonine residues, the resulting mutants were fully functional, implying that these two residues may serve as the autophosphorylation sites.

SIGNOR-83407

Q8TD08

2

phosphorylation

up-regulates

0.2

Erk8 (extracellular-signal-regulated protein kinase 8) expressed in escherichia coli or insect cells was catalytically active and phosphorylated at both residues of the thr-glu-tyr motif.Our results suggest that the activity of erk8 in transfected hek-293 cells depends on the relative rates of erk8 autophosphorylation

SIGNOR-142969

P42684

2

phosphorylation

up-regulates quantity by stabilization

0.2

The results show that Arg is stabilized in response to 0.1 mM H2O2 by autophosphorylation of Y-261, consistent with involvement of the Arg kinase function in regulating Arg levels. The results further demonstrate that c-Abl-mediated phosphorylation of Arg on Y-261 similarly confers Arg stabilization.. These findings indicate that abrogation of the Arg kinase function by the Y261F mutation is dependent on phosphorylation of the Y-439 site.

SIGNOR-276033

Q9Y2H1

2

phosphorylation

up-regulates

0.2

Ndr1/ndr2 protein kinase is activated by phosphorylation on the activation loop phosphorylation site ser281/ser282 and the hydrophobic motif phosphorylation site thr444/thr442. Autophosphorylation of ndr is responsible for phosphorylation on ser281/ser282, whereas thr444/thr442 is targeted by an upstream kinase. Here we show that mst3, a mammalian ste20-like protein kinase, is able to phosphorylate ndr protein kinase at thr444/thr442. In vitro, mst3 selectively phosphorylated thr442 of ndr2, resulting in a 10-fold stimulation of ndr activity.

SIGNOR-142518

Q9Y463

2

phosphorylation

up-regulates

0.2

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

SIGNOR-79810

P04629

2

phosphorylation

up-regulates

0.2

In vitro studies indicate that trka autophosphorylates at tyrosines 490, 670, 674, 675, and 785

SIGNOR-47171

P16234

2

phosphorylation

up-regulates activity

0.2

We have identified two autophosphorylation sites, Tyr-988 and Tyr-1018, in the platelet-derived growth factor (PDGF) alpha-receptor carboxyl-terminal tail, which are involved in binding of phospholipase C-gamma (PLC-gamma). We conclude that phosphorylated Tyr-988 and Tyr-1018 in the PDGF α-receptor carboxyl-terminal tail bind PLC-γ, but this association leads to only a relatively low level of tyrosine phosphorylation and activation of PLC-γ.

SIGNOR-250252

Q9UIK4

2

phosphorylation

down-regulates activity

0.2

Autophosphorylation restrains the apoptotic activity of DRP-1 kinase by controlling dimerization and calmodulin binding. | It comprises a single autophosphorylation event mapped to Ser308 within the CaM regulatory domain.

SIGNOR-251084

Q96BA8

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-224205

P22455

2

phosphorylation

up-regulates

0.2

Binding of fgf to fgf receptors leads to receptor dimerization and subsequent tyrosine autophosphorylation and phosphorylation of target substrates. Autophosphorylation on tyrosine is considered to have at least two functions. One such function is the stimulation of the intrinsic protein tyrosine kinase activity by an allosteric mechanismthis antibody specifically recognizes tyr642/643 in fgfr-4.

SIGNOR-179776

Q9H2K8

2

phosphorylation

up-regulates activity

0.2

These data indicate that JIK is indeed the protein kinase present in the immune complex responsible for autophosphorylation and for the phosphorylation of the exogenous substrate. Moreover, our observations suggest that JIK (A181F183) acts as the catalytically inactive mutant of JIK, which is no longer able to potently undergo autophosphorylation and dramatically phosphorylate MBP, as compared with the wild type JIK.

SIGNOR-246302

Q5VT25

2

phosphorylation

up-regulates activity

0.2

N terminus-mediated dimerization and transautophosphorylation are essential for MRCKα catalytic activity. Three mutations, S234A, T240A, and T403A, strongly affected the in vitro autophosphorylation activity of FLAG-MRCKα-CAT1–473 (Fig. (Fig.5D).5D).

SIGNOR-275974

O00329

2

phosphorylation

down-regulates

0.2

Autophosphorylation of p110delta phosphoinositide 3-kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo in vitro autophosphorylation of p110delta completely down-regulates its lipid kinase activity.

SIGNOR-65186

P42681

2

phosphorylation

up-regulates

0.2

Evidence of autophosphorylation in txk: y91 is an autophosphorylation site. the results suggest that phosphorylated txk is an active form to promote ifn-gamma synthesis

SIGNOR-89844

Q9NR20

2

phosphorylation

up-regulates activity

0.2

Autophosphorylation of DYRK4 in the Activation Loop Is Required for Kinase Activity

SIGNOR-260827

P29320

2

phosphorylation

up-regulates activity

0.2

Eph receptor activation leads to tyrosine phosphorylation of three major autophosphorylation sites. these residues function to regulate kinase activity, their phosphorylation being required for full intrinsic enzyme activity. these tyrosines (EphA3 Y596, Y602 and Y779) as the prominent autophosphorylation sites of EphA3

SIGNOR-251115

P22392

2

phosphorylation

up-regulates activity

0.2

Using site-directed mutagenesis of the cDNA encoding NM23-H2, we have created a mutant substituting for the amino acid histidine 118, the presumed site of phosphorylation in the formation of the phosphoenzyme intermediate, the nonphosphorylatable amino acid phenylalanine. The H118F mutant protein is shown to be catalytically inactive

SIGNOR-250304

Q99558

2

phosphorylation

up-regulates activity

0.2

As nik levels increase, nik presumably becomes activated by autophosphorylation (p).

SIGNOR-167063

Q16665

Q9H3R0

2

binding

up-regulates activity

0.2

In hypoxia, HIF-1α dimerizes with HIF-1β to form active HIF-1 complex. JMJD2C interacts with HIF-1α and promotes the transcriptional activation of HIF-1 targeting genes via demethylating di- and trimethylated H3K9.

SIGNOR-263873

O00635

2

polyubiquitination

down-regulates quantity by destabilization

0.2

Our study shows that, similar to other TRIM family members, TRIM38 is localized in the cytoplasm. TRIM38 increases ubiquitination of other cellular proteins and catalyzes self-ubiquitination. TRIM38 also promotes K63- and K48-linked ubiquitination of cellular proteins. An intact RING domain is important for the functions of TRIM38. In addition, enterovirus 71 infection induces TRIM38 degradation.

SIGNOR-271906

P49760

2

phosphorylation

up-regulates

0.2

Clk2 was reported to regulate its nuclear localization by autophosphorylating serine 141

SIGNOR-167344

P15531

2

phosphorylation

up-regulates activity

0.2

An acid-stable (nonhistidine) phosphorylation was identified on autophosphorylated purified recombinant Nm23 proteins and [32P]orthophosphate-labeled human breast carcinoma and murine melanoma Nm23. Phosphoamino acid analysis identified serine as the acid-stable phosphorylation and serine 44 as the major site of phosphorylation. The biological relevance of the novel phosphorylation identified herein is suggested by the direct correlation of in vivo Nm23 acid-stable phosphorylation levels, but not Nm23 NDPK activity, with suppression of tumor metastatic potential among control and nm23-1 transfected murine melanoma cells.

SIGNOR-250303

Q9UMX1

2

binding

up-regulates

0.2

Hsu(fu) associated with itself / homo- or heterodimers of hsu(fu) might function to bring together other effector proteins

SIGNOR-72311

Q9BXA7

2

phosphorylation

up-regulates activity

0.2

Electrospray Q‐TOF2 mass spectroscopy analysis of a trypsin digested TSSK1 purified from E. coli, revealed that it was phosphorylated at its T‐loop residue (Fig. 2D), indicating that TSSK1 as was previously shown for MELK [18], can autophosphorylate its T‐loop Thr residue.

SIGNOR-260823

O96013

2

phosphorylation

up-regulates

0.2

Intracellular localization;enzymatic activity, induced;cell growth, altered;

SIGNOR-168301

Q13330

Q8NHY2

2

polyubiquitination

down-regulates quantity by destabilization

0.2

Here we report that MTA1 is an ubiquitinated protein and targeted by the RING-finger E3 ubiquitin-protein ligase constitutive photomorphogenesis protein 1 (COP1) for degradation via the ubiquitin-proteasome pathway.

SIGNOR-271891

P21802

2

phosphorylation

up-regulates activity

0.2

Our data also show that tyrosine 769 is not involved in the regulation of the endocytic process of KGFR.Following ligand binding, KGFR is rapidly autophosphorylated on specific tyrosine residues

SIGNOR-276026

Q05655

2

phosphorylation

up-regulates

0.2

This study identifies novel in vitro pkcdelta autophosphorylation sites at thr(141) adjacent to the pseudosubstrate domain, thr(218) in the c1a-c1b interdomain, ser(295), ser(302), and ser(304) in the hinge region, and ser(503) adjacent to thr(505) in the activation loop. studies reported herein show that a t505a substitution reduces pkcdelta-thr(295) autophosphorylation

SIGNOR-185287

Q9UK32

2

phosphorylation

up-regulates activity

0.2

These mutants had minimal kinase activity and showed profoundly decreased phosphorylation at Ser232 compared with wild-type RSK4 (Fig 10B), suggesting that RSK4 can autophosphorylate at Ser232.

SIGNOR-275797

P00558

O15530

2

phosphorylation

up-regulates activity

0.2

PDPK1 Phosphorylates PGK1 T243. Macrophages increase PGK1 pT243 to reduce the 3-PG affinity of PGK1, which alters the equilibrium of the PGK1-catalyzed reaction toward glycolysis, promoting tumor cell proliferation.

SIGNOR-277402

P52564

2

phosphorylation

up-regulates activity

0.2

However, the autocatalytic activities of both mkk6 and mkk7 were enhanced by their coexpression with either mekk3 or mekk2.

SIGNOR-236122

Q92630

P30304

2

dephosphorylation

down-regulates activity

0.2

Finally, DYRK2 is dephosphorylated by CDC25A, suggesting a feedback regulatory loop.|Notably, the co-expression of CDC25A inhibited the DYRK2 pro-apoptotic effect (Fig.\u00a06D), concurring with a possible inhibitory role on DYRK2 activity and further suggesting that the effect of DYRK2 was dependent on CDC25A.

SIGNOR-277098

Q99759

2

phosphorylation

up-regulates

0.2

Phosphorylation of serine 526 is required for mekk3 activity, and association with 14-3-3 blocks dephosphorylationautophosphorylation of mekk3 at ser526

SIGNOR-143647

Q9Y4D8

P01106

2

transcriptional regulation

down-regulates quantity by repression

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-267144

Q13976

2

phosphorylation

up-regulates

0.2

Serines 64 and 79 are homologous residues that are juxtaposed to the autoinhibitory pseudosubstrate site in cgmp-dependent protein kinase type ialpha and type ibeta (pkg-ialpha and pkg-ibeta), respectively. Autophosphorylation of this residue is associated with activation of type i pkgs.

SIGNOR-89839

P31323

2

phosphorylation

up-regulates activity

0.2

Ser114 (the autophosphorylation site) of human RII beta. Point mutation of the autophosphorylation site or in the nuclear location signal causes protein kinase A RII beta regulatory subunit to lose its ability to revert transformed fibroblasts.

SIGNOR-250076

Q9UHD2

Q86WV6

2

binding

up-regulates activity

0.2

MAVS also interacts with STING that locates at the ER (endoplasmic reticulum), and induces the ubiquitination and dimerization of STING. The activated STING recruits TBK1 and IRF3 and contributes to the phosphorylation of IRF3 mediated by TBK1.

SIGNOR-260153

Q9Y6E0

2

phosphorylation

up-regulates

0.2

Inhibition of cell migration by autophosphorylated mammalian sterile 20-like kinase 3 (mst3) involves paxillin and protein-tyrosine phosphatase-pest.

SIGNOR-150131

Q9H0K1

2

phosphorylation

up-regulates activity

0.2

SIK2 S358 Autophosphorylation Is a Marker of SIK2 Activity

SIGNOR-277268

P34947

2

phosphorylation

up-regulates activity

0.2

Autophosphorylation of GRK5 occurs primarily at residues Ser-484 and Thr-485. Phospholipid-stimulated autophosphorylation activates the G protein-coupled receptor kinase GRK5.

SIGNOR-251201

O75460

2

phosphorylation

up-regulates activity

0.2

IRE1 transduces the unfolded protein response by splicing XBP1 through its C-terminal cytoplasmic kinase-RNase region. IRE1 autophosphorylation is coupled to RNase activity through formation of a back-to-back dimer, although the conservation of the underlying molecular mechanism is not clear from existing structures.

SIGNOR-275417

P18433

2

dephosphorylation

down-regulates activity

0.2

Transient overexpression of c-Src together with RPTP alpha in human embryonic kidney 293 cells increased phosphorylation of Tyr789, suggesting that c-Src may phosphorylate RPTP alpha in vivo. RPTP alpha had autodephosphorylation activity in vitro. When expressed in 293 cells the level of Tyr789 phosphorylation was higher in a non-functional mutant of RPTP alpha than in wild type RPTP alpha, indicating that RPTP alpha may have autodephosphorylation activity in vivo as well.|We show that RPTP alpha, but not a mutant of RPTP alpha with a Tyr-->Phe mutation at position 789, bound to GRB2 in vitro.

SIGNOR-248439

P12931

2

phosphorylation

down-regulates activity

0.2

Rapid digestion of pp60c-src tyrosine kinase (src TK) in combination with electrospray ionization mass spectrometry enabled the determination of the time course for autophosphorylation of three tyrosine sites (Y338, Y419, and Y530) and a correlation with src TK activity. Here, conditions were identified which promoted essentially complete autophosphorylation of y530. Phosphorylation of y530 was directly correlated to a decrease in tyrosine kinase activity

SIGNOR-43315

Q9BYT3

2

phosphorylation

up-regulates activity

0.2

Our results show that the serine/threonine kinase Stk33 phosphorylates the intermediate filament protein vimentin in vitro specifically in the vimentin head domain. Stk33 undergoes obligatory autophosphorylation, which might be a prerequisite for its kinasing activity.

SIGNOR-272957

Q13490

2

ubiquitination

down-regulates quantity by destabilization

0.2

Ciap1 and ciap2 undergo autoubiquitination and degradation upon binding to the iap antagonist second mitochondrial activator of caspases (smac)/direct iap-binding protein with low pi (diablo), which is released from the mitochondria.

SIGNOR-121877

O14641

2

binding

up-regulates activity

0.2

Dix domain of dvl2 mediates dynamic polymerization, which is essential for the signaling activity of dvl2.

SIGNOR-155224

Q96PN8

2

phosphorylation

up-regulates activity

0.2

We elucidated the mechanism of regulation of TSSK3 activity showing that autophosphorylation and PDK1 phosphorylation in the ‘activation loop’ are necessary for activation.

SIGNOR-260785

P42224

2

binding

up-regulates activity

0.2

Each STAT1 monomer becomes tyrosine phosphorylated at tyrosine 701 by the JAKs, dissociates from the receptor to form a STAT1-STAT1 homodimer which translocates to the nucleus

SIGNOR-249495

Q16236

O00625

2

binding

up-regulates activity

0.2

In contrast, the depletion of PIR initiates HMGB1-dependent autophagy by binding to BECN1, and subsequently promotes ferroptosis by activating ACSL4.

SIGNOR-279852

Q13315

P49959

2

binding

up-regulates

0.2

One of the earliest events is recruitment and activation of the atm at the damaged dna sites through the mre11rad50nbs1 (mrn) sensor complex. the mre11/rad50/nbs1 (mrn) complex maintains genomic stability by bridging dna ends and initiating dna damage signaling through activation of the atm kinase.

SIGNOR-175006

O43379

Q99759

2

binding

up-regulates quantity by stabilization

0.2

Specifically, we demonstrate that MEKK3 interacts with WDR62 to stabilize WDR62 and regulates JNK activity in a synergic way. On the other hand, JNK activity also regulates the phosphorylation of WDR62 at T1053 in a feedback loop which facilities the recruitment of FBW7 degradation of WDR62

SIGNOR-271714

Q8TF76

P53350

2

phosphorylation

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-275421

P40189

2

phosphorylation

up-regulates activity

0.2

The biological functions of interleukin-6 (IL-6) are mediated through a signal-transducing component of the IL-6 receptor, gp130, which is associated with the ligand-occupied IL-6 receptor (IL-6R) protein. Binding of IL-6 to IL-6R induced disulfide-linked homodimerization of gp130. Tyrosine kinase activity was associated with dimerized but not monomeric gp130 protein. Substitution of serine for proline residues 656 and 658 in the cytoplasmic motif abolished tyrosine kinase activation and cellular responses but not homodimerization of gp130.

SIGNOR-238625

Q16659

2

phosphorylation

up-regulates

0.2

Ser189 of erk3, which corresponds to thr183, one of the activating phosphorylation sites of erk2, is autophosphorylated in vitro and phosphorylated in vivo.

SIGNOR-40097

P29323

2

phosphorylation

up-regulates activity

0.2

Our results demonstrate that autophosphorylation tyrosine 611 in the juxtamembrane region of chicken EphB2 is critical for the association of the Src SH2 domain.

SIGNOR-251124

Q96J92

2

phosphorylation

down-regulates activity

0.2

Elimination of the catalytic activity (D321A or D321K-K186D) or the autophosphorylation site (S335A) in mutant WNK4-L322F abrogated the positive effect on NCC.

SIGNOR-276871

Q7Z569

2

ubiquitination

down-regulates quantity by destabilization

0.2

Here we report on a novel interaction between the E3 ligase BRAP (also referred to as IMP), a negative regulator of the MAPK scaffold protein KSR, and two closely related deubiquitylases, USP15 and USP4. USP15 as well as USP4 oppose the autoubiquitylation of BRAP, whereas BRAP promotes the ubiquitylation of USP15.

SIGNOR-272027

Q86WV6

Q9UHD2

2

phosphorylation

up-regulates activity

0.2

MITA was phosphorylated by TBK1, which is required for MITA-mediated activation of IRF3. Our results suggest that MITA is a critical mediator of virus-triggered IRF3 activation and IFN expression and further demonstrate the importance of certain mitochondrial proteins in innate antiviral immunity. Consistent with its inability to activate IRF-E, the mutation of S358 to alanine impaired the ability of MITA to interact with TBK1 and to enhance the interaction between TBK1 and IRF3

SIGNOR-263136

Q13470

2

phosphorylation

up-regulates activity

0.2

We found a similar reduction in the levels of phosphorylation of Tyr277, which corresponds to the predicted major site of autophosphorylation within the activation loop of Tnk1 (Fig. 3C).

SIGNOR-274126

P09619

P25098

2

phosphorylation

down-regulates activity

0.2

In 293 cells, GRK2 overexpression reduced PDGFRbeta/NHERF association by 60%.

SIGNOR-278379

Q9BZL6

2

phosphorylation

up-regulates

0.2

The addition of phorbol 12,13-dibutyrate in the presence of dioleoylphosphatidylserine stimulated the autophosphorylation of pkd2 in a synergistic fashion.In addition, we could identify the c-terminal ser(876) residue as an in vivo phosphorylation site within pkd2. Phosphorylation of ser(876) of pkd2 correlated with the activation status of the kinase.

SIGNOR-83834

P23470

2

binding

down-regulates activity

0.2

The main regulatory mechanism of RPTP activity consists of the reversible transition from a homodimeric inactive form to a monomeric active form. PTPRG is constitutively expressed on monocyte plasma membrane as a homodimer with the WD involved in catalytic domain blockade.

SIGNOR-254737

O75914

2

phosphorylation

up-regulates activity

0.2

Both in vivo and in vitro analyses demonstrate that, although most phosphorylation events in the PAK N-terminal regulatory domain play no direct role in activation, a phosphorylation of alphaPAK serine 144 or betaPAK serine 139, which lie in the kinase inhibitory domain, significantly contribute to activation.

SIGNOR-250245

P20794

2

phosphorylation

up-regulates activity

0.2

We conclude that dual phosphorylation on the TDY motif is crucial for MAK activity, and that the autokinase activity is required for this phosphorylation

SIGNOR-260779

P29322

2

phosphorylation

up-regulates activity

0.2

Tyr-615 and Tyr-838 are major autophosphorylation sites of the EphA8 receptor. phosphorylation of Tyr-615 is critical for determining the association with Fyn whereas the integrity of Tyr-838 phosphorylation is required for efficient phosphorylation at Tyr-615 as well as other major sites.

SIGNOR-251121

Q9H3R0

Q16665

2

transcriptional regulation

up-regulates quantity by expression

0.2

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271570

P17612

Q02952

2

relocalization

up-regulates activity

0.2

A-kinase-anchoring protein 250 (AKAP250; gravin) acts as a scaffold that binds protein kinase A (PKA), protein kinase C and protein phosphatases, associating reversibly with the beta(2)-adrenergic receptor.

SIGNOR-271835

P49841

2

phosphorylation

up-regulates activity

0.2

Phosphorylation of the residue Tyrosine in 216 position results in the constitutive activity of GSK-3beta and believed to be important target for signal transduction.

SIGNOR-217865

O00418

2

phosphorylation

down-regulates

0.2

The combination of eef2k autophosphorylation (targeting ser445) and a yet to be identified kinase (targeting ser441) would be needed to generate the eef2k phosphodegron specifically in response to dna damage.

SIGNOR-197725

Q15796

2

binding

up-regulates activity

0.2

Smad2 and Smad3 form homo-oligomers upon phosphorylation by the constitutively active TGF-beta type I receptor, and this oligomerization does not require Smad4

SIGNOR-232149

P12644

2

binding

up-regulates

0.2

Bmps are dimeric proteins with a single inter-chain disulfide bond. The dimeric conformation is anabsolute requirement for the biological action and interaction with receptors

SIGNOR-236169

P09769

2

phosphorylation

up-regulates activity

0.2

Autophosphorylation of c-Fgr under basal conditions involves Tyr-400 (homologous of c-Src Tyr-416) but not, to any appreciable extent, Tyr-511. Both Tyr-511 and Tyr-400, however, incorporate phosphate if autophosphorylation is performed in the presence of polycationic peptides, such as polylysine, histones H1 and protamines. Such a double phosphorylation induced by polylysine gives rise to an upshifted form of c-Fgr on SDS-PAGE and correlates with a stimulation of catalytic activity instead of a down-regulation

SIGNOR-251143

P17252

2

phosphorylation

up-regulates

0.2

Pkc is frequently autophosphorylated on two c-terminal sites, the turn motif (thr- 638 in human pkc) and the hydrophobic site (ser-657 in human pkc). Thus, it is becoming clear that autophosphorylation of pkc can be a regulated event and that it has significant impact on pkc function

SIGNOR-127253

O75676

2

phosphorylation

up-regulates activity

0.2

Here we report that the CK2 protein kinase, which contributes to NF-kappaB activation following UV radiation in a p38-dependent manner, physically interacts with MSK2 but not MSK1 and that CK2 inhibition specifically impairs UV-induced MSK2 kinase activation. A putative site of CK2 phosphorylation was mapped to MSK2 residue Ser(324) and when substituted to alanine (S324A) also compromised MSK2 activity.Serine 324 is required for UV-induced MSK2 activation and for autophosphorylation at MSK2-Ser196.

SIGNOR-276269