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Substrate SpecificityTyrosineMolecular Sequence DataAmino Acid SequenceKineticsSensitivity and SpecificityProtein Tyrosine PhosphatasesBinding SitesPhosphorylationModels, MolecularRecombinant ProteinsCatalysisSequence Homology, Amino AcidBase SequenceTyrosine 3-MonooxygenaseCatalytic DomainProtein BindingEscherichia coliMutagenesis, Site-DirectedHydrolysisProtein Structure, TertiaryCloning, MolecularCrystallography, X-RayMutationHydrogen-Ion ConcentrationProtein ConformationSequence AlignmentStructure-Activity RelationshipCell LineSignal TransductionEnzyme ActivationPhosphotyrosineIsoenzymesBacterial ProteinsMolecular WeightElectrophoresis, Polyacrylamide GelRecombinant Fusion ProteinsSpecies SpecificityAmino AcidsAntibody SpecificityPeptidesAmino Acid SubstitutionEnzyme InhibitorsProtein Tyrosine Phosphatase, Non-Receptor Type 11Molecular StructureDNA PrimersPhosphoproteinsEnzyme StabilityOligopeptidesReceptor Protein-Tyrosine KinasesProtein Tyrosine Phosphatase, Non-Receptor Type 6TransfectionCells, CulturedChromatography, High Pressure LiquidCattleAmino Acid MotifsTemperatureDNA, ComplementaryProtein Structure, SecondaryStereoisomerismOxidation-ReductionSerine EndopeptidasesEndopeptidasesDNAProtein KinasesCarrier ProteinsModels, ChemicalSaccharomyces cerevisiaeAlcohol OxidoreductasesProtein Tyrosine Phosphatase, Non-Receptor Type 1ProteinsMembrane ProteinsEscherichia coli ProteinsLiverPhenylalanineChromatography, GelPhylogenyCarbohydrate SequenceProtein EngineeringBiological Transportsrc Homology DomainsPeptide FragmentsProto-Oncogene ProteinsAdenosine TriphosphateIntracellular Signaling Peptides and ProteinsAcyltransferasesCell MembraneBlotting, WesternProtein Processing, Post-TranslationalCOS CellsModels, BiologicalVanadatesPlasmidsPeptide LibraryTime FactorsOxidoreductasesOligosaccharidesGlycoside HydrolasesConserved SequenceMutagenesis

KinasesPhosphorylationKinaseResiduesPhosphataseSignal transductionEnzymePhosphatasesMammalianEnzymesMechanismBiochemicalAromaticIntracellularStructuralBiosynthesisPhenylalanineResidueDecarboxylaseConformational changeProteinsCharacteristicsRecognitionRecognizesEffectorEthylReactionTemperatureCatalyzesAminoCompoundsDeterminesFamilyActivityActive site

Kinases30

• TNK2 gene encodes a non-receptor tyrosine kinase, ACK1, that binds to multiple receptor tyrosine kinases e.g. (wikipedia.org)
• Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. (embl.de)
• Dual specificity protein kinases (e.g. (embl.de)
• The specificity of tyrosine kinases is attributed predominantly to localization effects dictated by non-catalytic domains. (escholarship.org)
• We developed a method to profile the specificities of tyrosine kinases by combining bacterial surface-display of peptide libraries with next-generation sequencing. (escholarship.org)
• Using this approach, we find a difference in the electrostatic recognition of substrates between the closely related Src-family kinases Lck and c-Src. (escholarship.org)
• Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. (rcsb.org)
• This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. (rcsb.org)
• It does not include the catalytic domain of dual specificity kinases. (rcsb.org)
• Protein tyrosine kinases are key enzymes of mammalian signal transduction. (johnshopkins.edu)
• Substrate specificity is a fundamental property that determines the specificity and fidelity of signaling by protein tyrosine kinases. (johnshopkins.edu)
• However, how protein tyrosine kinases recognize the protein substrates is not well understood. (johnshopkins.edu)
• Although both Csk and MAP kinases used docking sites for substrate recognition, their docking sites consisted of different substructures in the catalytic domain. (johnshopkins.edu)
• This model may provide a framework for understanding substrate recognition and specificity of other protein tyrosine kinases. (johnshopkins.edu)
• I also examined the substrate specificities of more than 200 human protein kinases with peptide microarrays populated with semi-optimal substrate sequences. (dissertation.com)
• Homeodomain-interacting protein kinases (HIPKs) belong to the CMGC kinase family and are closely related to dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs). (nature.com)
• HIPKs belong to the CMGC group of serine/threonine kinases and are part of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. (nature.com)
• Dual specificity phosphatase 3 (DUSP3), a suppressor of multiple protein tyrosine (Tyr) kinases, is decreased in lung cancer tissues. (biomedcentral.com)
• DUSP3/VHR, related to the vaccinia virus phosphatase VH1, is initially found to be a phosphatase that dephosphorylates multiple protein tyrosine kinases (PTKs) in vitro [ 21 ]. (biomedcentral.com)
• Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. (nih.gov)
• The receptor tyrosine kinases were the 1st mammalian receptors shown to be ubiquitinated inside a ligand-dependent manner (7, 8). (oaxacalibre.net)
• Two of the introns in HB5 are not found in other genes of this family, suggesting an evolutionary split between MKPs displaying specificity toward different MAP kinases. (ox.ac.uk)
• We have previously examined the specificities of 28 commercially available compounds, reported to be relatively selective inhibitors of particular serine/threonine-specific protein kinases [Davies, Reddy, Caivano and Cohen (2000) Biochem. (nih.gov)
• Our results suggest that the combined use of Roscovitine and Kenpaullone may be useful for identifying substrates and physiological roles of cyclin-dependent protein kinases, whereas the combined use of Kenpaullone and LiCl may be useful for identifying substrates and physiological roles of glycogen synthase kinase 3. (nih.gov)
• The substrate specificities of the ERK1 and ERK2 protein kinases are very similar. (proteinkinase.biz)
• Gonzalez FA, Raden DL, Davis RJ (1991) "Identification of substrate recognition determinants for human ERK1 and ERK2 protein kinases" J. Biol. (proteinkinase.biz)
• 1996) "A structural basis for substrate specificities of protein Ser/Thr kinases: primary sequence preference of casein kinases I and II, NIMA, phosphorylase kinase, calmodulin-dependent kinase II, CDK5, and Erk1" Mol Cell Biol. (proteinkinase.biz)
• The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases. (umbc.edu)
• DYRK2 (also known as dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 2) belongs to a family of protein kinases whose members are presumed to be involved in cellular growth and/or development and is defined by structural similarity of their kinase domains and their capability to autophosphorylate on tyrosine residues. (signalchem.com)
• 1. Becker, W. et.al: Sequence characteristics, subcellular localization, and substrate specificity of DYRK-related kinases, a novel family of dual specificity protein kinases. (signalchem.com)

Phosphorylation9

• The protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation signal transduction pathway. (wikipedia.org)
• ACK1 interaction with its substrates resulted in their phosphorylation at specific tyrosine residues. (wikipedia.org)
• Protein tyrosine (pTyr) phosphorylation is a common post-translational modification which can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. (embl.de)
• Consequently, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. (embl.de)
• 2016). Here, we expand this high-throughput platform to analyze the intrinsic specificity of any tyrosine kinase domain against thousands of peptides derived from human tyrosine phosphorylation sites. (escholarship.org)
• They regulate all cellular processes by transducing inter- and intracellular signals via the phosphorylation of specific protein substrates. (dissertation.com)
• DUSP3 regulated OCLN ubiquitination and degradation through decreasing OCLN tyrosine phosphorylation directly or through suppressing focal adhesion kinase, the OCLN kinase. (biomedcentral.com)
• Microbial infection) Acts as a receptor for human cytomegalovirus protein UL11 and mediates binding of UL11 to T-cells, leading to reduced induction of tyrosine phosphorylation of multiple signaling proteins upon T-cell receptor stimulation and impaired T-cell proliferation. (neobiotechnologies.com)
• DYRK2 expressed in E. coli demonstrated tyrosine autophosphorylation and catalyzed phosphorylation of histones H3 and H2B in vitro (1). (signalchem.com)

Kinase12

• Biochemical properties of the Cdc42-associated tyrosine kinase ACK1. (wikipedia.org)
• Using this, we showed that the tyrosine kinase ZAP-70, which is critical for T cell signaling, discriminates substrates through an electrostatic selection mechanism encoded within its catalytic domain (Shah et al. (escholarship.org)
• These results point to the importance of direct recognition at the kinase active site in fine-tuning specificity. (escholarship.org)
• The resultant data were used to expand the training datasets for development of next generation protein kinase substrate predictive algorithms. (dissertation.com)
• For the class II DYRK ortholog from D. melanogaster it was demonstrated that the critical tyrosine is cis -auto-phosphorylated by the nascent kinase in a transitory intermediate state during maturation at the ribosome 3 . (nature.com)
• Upon ligand binding the receptor tyrosine kinase is definitely autophosphorylated, leading to recruitment of Cbl, a RING-type E3 ligase, which results in receptor ubiquitination, internalization, and lysosomal degradation. (oaxacalibre.net)
• Suitable as substrate for kinase activity assays and for western blot analyses. (proteinkinase.biz)
• They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. (umbc.edu)
• B) dCK kinase assay using CHOC6 nuclear ABT-888 (Veliparib) and cytoplasmic fraction lysates, [3H]-dC as substrate and performed 2 hours after exposure to 3 Gy (*, P? (biomasswars.com)
• D) dCK kinase assay using L1210 nuclear and cytoplasmic fraction lysates, [3H]-dC as substrate and performed 2 hours after exposure to 3 Gy (*, P? (biomasswars.com)
• Insulin-stimulated glucose transport in isolated skeletal muscle was reduced 47% in obese versus lean rats, with a parallel 42% reduction in tyrosine-associated PI 3-kinase activity. (diabetesjournals.org)
• This most likely occurs from defects in postreceptor insulin signal transduction at the level of insulin receptor substrate-1 and phosphoinositide (PI) 3-kinase ( 6 - 9 ) as well as defects in trafficking and/or function of GLUT4 ( 10 , 11 ), the major insulin-regulated GLUT isoform expressed in skeletal muscle ( 12 ). (diabetesjournals.org)

Residues6

• ACK1 has been shown to directly phosphorylate AKT at tyrosine 176, AR at Tyrosine 267 and 363, and WWOX at tyrosine 287 residues, respectively. (wikipedia.org)
• Those which bind phosphorylated tyrosine residues may recruit multi-phosphorylated substrates for the adjacent active domains and are more conserved, while the other class have accumulated several variable amino acid substitutions and have a complete loss of tyrosine binding capability. (embl.de)
• A shallow active site pocket in VHR allows for the hydrolysis of phosphorylated serine, threonine, or tyrosine protein residues, whereas the deeper active site of protein tyrosine phosphatases (PTPs) restricts substrate specificity to only phosphotyrosine. (rcsb.org)
• Positively charged crevices near the active site may explain the enzyme's preference for substrates with two phosphorylated residues. (rcsb.org)
• however, dGTPase residues at the end of the substrate-binding pocket mimic Watson Crick interactions providing Guanine base specificity, while a 7 Å cleft separates SAMHD1 residues from dNTP bases, abolishing nucleotide-type discrimination. (biorxiv.org)
• DYRKs are named after their characteristic dual-specificity, as they auto-phosphorylate a conserved tyrosine in their activation loop, but phosphorylate substrates on serine and threonine residues 2 . (nature.com)

Phosphatase7

• The catalytic domain of this dual-specificity phosphatase has recently been mapped to the 180 most C-terminal amino acids. (embl.de)
• CD45R functions as a phosphor-tyrosine phosphatase. (neobiotechnologies.com)
• Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor. (neobiotechnologies.com)
• The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. (nih.gov)
• DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases. (nih.gov)
• Expression of Dual-Specificity Phosphatase 9 in Placenta and Its Relationship with Gestational Diabetes Mellitus. (nih.gov)
• In this work, it is show that two unrelated domains, a VSD from voltage dependent ion channels and a lipid PD homologous to protein tyrosine phosphatases evolved a tight mechanism of allosteric regulation that transduces fluctuations in membrane potential into changes in the enzyme selectivity of a novel lipid phosphatase. (escholarship.org)

Signal transduction1

• Dual specificity protein phosphatases (DSPs) regulate mitogenic signal transduction and control the cell cycle. (rcsb.org)

Enzyme6

• EC 3.1.3.48 ) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. (embl.de)
• The enzyme showed broad substrate specificity toward natural and synthetic l-amino acids. (unipr.it)
• A structural mechanism for enzyme catalysis and substrate specificity is proposed, in which a helix dipole and a hydrogen bond triad of Y216, S150 and E15 assist the binding of two D-alanine substrates. (uconn.edu)
• Molecular dynamics simulations using the crystal structures of Trypanosoma cruzi TAT and human TAT provided further insight regarding the substrate-enzyme interactions and substrate specificity. (rhea-db.org)
• Using a pair of new PIP sensors to monitor enzyme activity and voltage clamp fluorometry to monitor conformational changes in the VSD, it becomes clear the Ciona intestinalis VSP (Ci-VSP) has two distinct voltage regulated enzyme active states: a faster low-voltage state with substrate preference for PIP3 and a slower high-voltage state with preference for PIP2. (escholarship.org)
• This novel 2-step allosteric switch for enzyme specificity enables membrane potential to function as an allosteric effector that dynamically regulates PIP concentration. (escholarship.org)

Phosphatases1

• This entry represents the PTPase domain found in several tyrosine-specific protein phosphatases (PTPases). (embl.de)

Mammalian1

• Intensive studies have characterized the effective of PLP-binding and the substrate specificity of mammalian 3,4-dihydroxyphenyl-L-alanine (Dopa) decarboxylases, a member of group II PLP-dependent decarboxylase. (hokudai.ac.jp)

Enzymes3

• The last distinct group of AA5_2 enzymes based on substrate specificity are the raffinose-specific oxidases ( EC 1.3.3.- ). (cazypedia.org)
• Although plant and animal enzymes share extensive amino acid similarity, they display striking differences in their substrate specificities. (unipr.it)
• PIP concentrations are controlled by enzymes, including VSP, which has broad specificity for a diverse class of PIPs. (escholarship.org)

Mechanism2

• These results helped establish a docking-based substrate recognition mechanism for Csk. (johnshopkins.edu)
• Furthermore, the structures sheds light into the mechanism by which long distance binding (25 Å) of single stranded DNA in an allosteric site primes the active site by conformationally "opening" a tyrosine gate allowing enhanced substrate binding. (biorxiv.org)

Biochemical2

• Tyrosine aminotransferase: biochemical and structural properties and molecular dynamics simulations. (rhea-db.org)
• The objective of this study is to investigate its biochemical and structural characteristics and substrate specificity in order to provide insight regarding its involvement in these diseases. (rhea-db.org)

Aromatic1

• Tyrosine aminotransferase (TAT) catalyzes the transamination of tyrosine and other aromatic amino acids. (rhea-db.org)

Intracellular1

• Activation of dCK shifts its substrate specificity toward deoxycytidine, increases intracellular dCTP pools post IR, and enhances the rate of DNA repair. (biomasswars.com)

Structural1

• From this structural information and a sequence comparison, it is proposed that a DD-ligase-like structure without a 'molecular filter' is responsible for the broadened specificity of D-Ala:D-Lac ligase (VanA) found in vancomycin-resistant strains of Enterococcus. (uconn.edu)

Biosynthesis1

• Wang R, Han X, Xu S, Xia B, Jiang Y, Xue Y, Wang RR (2019) Cloning and characterization of a tyrosine decarboxylase involved in the biosynthesis of galanthamine in Lycoris aurea PeerJ 7 e6729. (unipr.it)

Phenylalanine2

• We obtained ancestral phenylalanine/tyrosine ammonia-lyases with substantially enhanced thermostability and long-term stability in Paper III and ancestral iduronate-2-sulfatases with increased activity in Paper IV . (kth.se)
• Here, we found that this strategy produced low-efficiency Ma PylRSs for encoding three structurally diverse ncAAs: acridonyl-alanine (Acd), 3-nitro-tyrosine, and m-methyl-tetrazinyl-phenylalanine (Tet3.0-Me). (oregonstate.edu)

Residue1

• It also leads to a qualitative explanation for the thermodynamic data on sugar-binding to the lectin, with special emphasis on the role of a tyrosyl residue in the variable loop in the sugar-binding region in generating the carbohydrate specificity of WBAII. (unboundmedicine.com)

Decarboxylase3

• Plant tyrosine decarboxylase (TyrDC) is a group II pyridoxal 5'-phosphate (PLP)-dependent decarboxylase that mainly catalyzes the decarboxylation of tyrosine to tyramine. (hokudai.ac.jp)
• Kalb D, Gressler J, Hoffmeister D (2016) Active-Site Engineering Expands the Substrate Profile of the Basidiomycete L-Tryptophan Decarboxylase CsTDC Chembiochem 17 132-6. (unipr.it)
• Lehmann T, Pollmann S (2009) Gene expression and characterization of a stress-induced tyrosine decarboxylase from Arabidopsis thaliana FEBS Lett. (unipr.it)

Conformational change1

• TY - JOUR T1 - Carbohydrate specificity and salt-bridge mediated conformational change in acidic winged bean agglutinin. (unboundmedicine.com)

Proteins3

• Additionally, I describe a novel method to produce a more unbiased polyclonal generic phosphotyrosine antibody than the monoclonal antibodies that are commonly used to enrich and track tyrosine-phosphorylated proteins. (dissertation.com)
• The conjugation of ubiquitin to a receptor prospects to the recruitment of ubiquitin-binding proteins, adaptors that mediate transport of the substrate to the proteasome or lysosome for degradation. (oaxacalibre.net)
• In contrast, substrates of the 11 cellular MARCH proteins remain only partially characterized (11), but two MARCH proteins, MARCH1 and MARCH8, down-regulate MHC class II molecules as well as CD86 indicated on antigen-presenting cells including dendritic cells and B cells. (oaxacalibre.net)

Characteristics2

• However, the characteristics of PLP binding and substrate specificity of plant TyrDCs remain unknown. (hokudai.ac.jp)
• Such characteristics of PLP binding may be required by its catalytic reaction and substrate binding. (hokudai.ac.jp)

Recognition2

• A "recognition region," connecting helix alpha1 to strand beta1, may determine differences in substrate specificity between VHR, the PTPs, and other DSPs. (rcsb.org)
• In the current study, we identified the docking determinants in Src recognized by the Csk substrate-docking site and demonstrated an interaction between the docking determinants of Src and the Csk substrate-docking site for this recognition. (johnshopkins.edu)

Recognizes1

• We have previously determined that Csk recognizes Src using a substrate-docking site away from the active site. (johnshopkins.edu)

Effector1

• This regulation of active site specificity in the PD by an allosteric effector domain represents a significant advancement in our understanding of allosteric regulation, which has previously been restricted to control of activity on only one type of substrate. (escholarship.org)

Ethyl2

• The analysis of the results indicated that the protease could hydrolyze N-Acetyl L-tyrosine ethyl ester but had no detectable activity on Succinyl tri-LAlanyl p-nitroanilide and L-N-BenzoylDZ arginine p-nitroanilide. (envirobiotechjournals.com)
• After incubation with LSD synthetic substrates, extracts are cleaned using liquid-liquid extraction with ethyl acetate or protein precipitation using acetonitrile (ACN). (cdc.gov)

Reaction1

• This last reaction is definitely catalyzed by one of around 400 ubiquitin E3 ligases that associate with the substrate and thus confer specificity to the ubiquitin reaction (6). (oaxacalibre.net)

Temperature2

• Fn-TPL was found to be a tetramer, and the optimal temperature and pH for α, β-elimination of l-tyrosine was 60 C and pH 8.5, respectively. (unipr.it)
• The protease produced by this organism was further tested for substrate specificity, temperature and pH stability studies. (envirobiotechjournals.com)

Catalyzes1

• Tyrosine phenol-lyase (TPL) catalyzes the reversible cleavage of l-tyrosine to phenol, pyruvate and ammonia. (unipr.it)

Amino1

• The recombinant mTAT is able to catalyze the transamination of tyrosine using α-ketoglutaric acid as an amino group acceptor at neutral pH. (rhea-db.org)

Compounds1

• The AA5_1 members are generally known as glyoxal oxidases ( EC 1.2.3.15 ), characterized members of which typically accept a range of simple aldehydes, α-hydroxycarbonyl, and α-dicarbonyl compounds as substrates, with the highest activities observed on glyoxal, methylglyoxal and glycolaldehyde [ 1 , 14 , 18 , 19 , 20 ]. (cazypedia.org)

Determines1

• The notion of a 'molecular filter' of tyrosine is introduced, which determines the substrate linkage specificity. (uconn.edu)

Family2

• Substrate specificity in glycoside hydrolase family 10. (dsmz.de)
• The combined use of SU 6656 and either PP1 or PP2 may be useful for identifying substrates of Src family members. (nih.gov)

Activity2

• The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. (neobiotechnologies.com)
• In Paper I , we established the utility of this method in a model system and obtained ancestral terpene cyclases with increased activity, stability and substrate scope. (kth.se)

Active site3

• The structure features a highly dynamic active site where conformational changes are coupled to substrate (dGTP), but not inhibitor binding, since GTP locks dGTPase in its apo form. (biorxiv.org)
• Tyrosine 87 and leucine 314 play a pivotal role in discriminating between glucose and xylose binding in the proximal active site of Pseudomonas cellulosa xylanase 10A. (dsmz.de)
• Prior work focused on "transplanting" ncAA substrate specificity by reconstructing the same active site mutations found in functional Mm/Mb PylRSs in Ma PylRS. (oregonstate.edu)