ReceptorPhosphorylationProteinsBindsIncrease in intracellularResiduesReceptorsSignal transductionTyrosine kinaseGuanylyl cyclaseSubfamilyActivitySubstratesHighly conservedEukaryoticKinase domainTransmembrane V0 domainSubunitProtein Tyrosine PhATPaseGranulesAmino acidKinesinDual-specificityMutationsPTKcRTKsShown to bind phospholipidsMembraneSegmentStructuralMembranesPathwayRegulationEnzymeClostridiumMechanismRegulatory domainsPathwaysRegionBindStructuresConcentrationsBacteriaMoleculeConformationFunctionOrganelles
Receptor27
- They are all cell surface receptors and designated: guanylyl cyclase-A (GC-A) also known as natriuretic peptide receptor-A (NPRA/ANPA) or NPR1 guanylyl cyclase-B (GC-B) also known as natriuretic peptide receptor-B (NPRB/ANPB) or NPR2 natriuretic peptide clearance receptor (NPRC/ANPC) or NPR3 NPR-A and NPR-B have a single membrane-spanning segment with an extracellular domain that binds the ligand. (wikipedia.org)
- RET consists of 3 domains, including a cysteine-rich extracellular receptor domain, a hydrophobic transmembrane domain, and an intracellular tyrosine kinase catalytic domain. (medscape.com)
- Unlike other members of the tumor necrosis factor receptor superfamily of transmembrane proteins, CD271 has unique intracellular domain structure (lacks catalytic activity) and downstream signaling partners. (exbio.cz)
- The proteases involved are of different origins and types: (i) present as precursor in plasma, (ii) secreted into the plasma by activated platelets or other blood cells, or (iii) intracellularly activated and cleaving cytosolic receptor domains. (frontiersin.org)
- Structurally, all known receptor PTPases, are made up of a variable length extracellular domain, followed by a transmembrane region and a C-terminal catalytic cytoplasmic domain. (embl.de)
- Some of the receptor PTPases contain fibronectin type III (FN-III) repeats, immunoglobulin-like domains, MAM domains or carbonic anhydrase-like domains in their extracellular region. (embl.de)
- NMR structure of the death domain of the p75 neurotrophin receptor. (embl-heidelberg.de)
- The intracellular domain of the p75 neurotrophin receptor (p75ICD) lacks catalytic activity but contains a motif similar to death domains found in the cytoplasmic regions of members of the tumor necrosis factor receptor family and their downstream targets. (embl-heidelberg.de)
- Unlike the death domains involved in signaling by the TNF receptor and Fas, p75ICD does not self-associate in solution. (embl-heidelberg.de)
- An antagonist decoy receptor and a death domain-containing receptor for TRAIL. (embl-heidelberg.de)
- TRAIL, also called Apo2L, is a cytotoxic protein that induces apoptosis of many transformed cell lines but not of normal tissues, even though its death domain-containing receptor, DR4, is expressed on both cell types. (embl-heidelberg.de)
- An antagonist decoy receptor (designated as TRID for TRAIL receptor without an intracellular domain) that may explain the resistant phenotype of normal tissues was identified. (embl-heidelberg.de)
- Extracellularly the receptor is made up of five immunoglobulin-like domains. (creation.com)
- The receptor makes a single pass through the cell membrane and contains an intracellular kinase catalytic region divided by a hydrophilic insert. (creation.com)
- V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, and receptor-mediated endocytosis. (nih.gov)
- Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. (unl.edu)
- Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. (unl.edu)
- Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta. (umbc.edu)
- PDGFR beta is a receptor tyr kinase (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. (umbc.edu)
- The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. (umbc.edu)
- To look for the structural basis for HER3 signaling through heterodimerization using a catalytically energetic HER receptor we resolved the crystal framework from the heterodimeric complicated formed with the isolated kinase domains of Meclofenoxate HCl EGFR and HER3. (bio-biz-navi.com)
- Launch Receptor tyrosine kinases play a significant role along the way of converting different extracellular cues in to the activation of distinctive intracellular signaling systems. (bio-biz-navi.com)
- Activation from the HER category of receptors takes place upon binding of extracellular ligands that Meclofenoxate HCl promote receptor oligomerization and catalytic activation from the intracellular kinase domains. (bio-biz-navi.com)
- The kinase domains of HER3 includes many inactivating substitutions that bring about an almost comprehensive lack of catalytic activity and HER3 is normally thus denoted being a pseudokinase receptor. (bio-biz-navi.com)
- Over the years multiple mechanisms of regulation of GC-C activity has been identified including allosteric controlled by various domains in the receptor and phosphorylation-mediated regulation of guanylyl cyclase activity. (iisc.ac.in)
- This acidification process is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. (nih.gov)
- The heavy chain is responsible for both receptor some species of the genus Clostridium, in particular, Clostridium binding via its C-terminal (CT) binding domain [4,5] (HC) and botulinum, C. butyricum, C. baratii, and C. argentinense. (cdc.gov)
Phosphorylation5
- They regulate all cellular processes by transducing inter- and intracellular signals via the phosphorylation of specific protein substrates. (dissertation.com)
- They all share a conserved catalytic core for their phosphotransferase function and often a common activation mechanism by phosphorylation of a variable segment known as the activation T-loop. (dissertation.com)
- This has led to the development of a range of ERK1/2 inhibitors (ERKi) that either inhibit kinase catalytic activity (catERKi) or additionally prevent the activating pT-E-pY dual phosphorylation of ERK1/2 by MEK1/2 (dual-mechanism or dmERKi). (babraham.ac.uk)
- BACKGROUND: Control of intracellular events by protein phosphorylation is promoted by specific protein kinases. (ox.ac.uk)
- Following phosphorylation of intracellular parts of the receptors triggers activation and recruitment of downstream components initiating signaling cascades. (bio-biz-navi.com)
Proteins16
- The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. (nih.gov)
- The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. (nih.gov)
- A majority of PX domain containing proteins binds phosphatidylinositol-3-phosphate (PI3P) at this site. (nih.gov)
- There are 37989 PTPc domains in 29134 proteins in SMART's nrdb database. (embl.de)
- Taxonomic distribution of proteins containing PTPc domain. (embl.de)
- The complete taxonomic breakdown of all proteins with PTPc domain is also avaliable . (embl.de)
- Click on the protein counts, or double click on taxonomic names to display all proteins containing PTPc domain in the selected taxonomic class. (embl.de)
- DEATH domain, found in proteins involved in cell death (apoptosis). (embl-heidelberg.de)
- Alpha-helical domain present in a variety of proteins with apoptotic functions. (embl-heidelberg.de)
- There are 10756 DEATH domains in 10503 proteins in SMART's nrdb database. (embl-heidelberg.de)
- This domain occurred 45 times on human genes ( 89 proteins). (umbc.edu)
- The proteasome complex is a broad spectrum protease present in all eukaryotes, which functions to carry out selective, efficient and progressive hydrolysis of intracellular target proteins. (tocris.com)
- Family members have conserved ligand-binding, catalytic (guanylyl cyclase) and regulatory domains with the exception of NPR-C which has an extracellular binding domain homologous to that of other NPRs, but with a truncated intracellular domain which appears to couple, via the G i/o family of G proteins, to activation of phospholipase C, inwardly-rectifying potassium channels and inhibition of adenylyl cyclase activity [ 19 ]. (guidetopharmacology.org)
- C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. (utsouthwestern.edu)
- This domain occurred 101 times on human genes ( 255 proteins). (umbc.edu)
- This protein belongs to the ROCO (ROC and COR domain) protein family and is made up of five characteristic functional domains: leucine-rich repeats (LRR domain), Rasp of complex proteins (ROC domain), C-terminal of Roc (COR domain), mitogen activated protein kinase kinase kinase (MAPKKK domain), and the WD40 domain. (biomedcentral.com)
Binds5
- Omecamtiv mecarbil is a novel, selective cardiac myosin activator, also known as a cardiac myotrope, 2 that binds to the catalytic domain of myosin. (amgen.com)
- upon elevation of Ca2+ and IP4 concentrations, the PH domain binds to IP4 thereby stimulating catalytic activity, while at the same time the C2a domain takes over the role of membrane tether. (sdbonline.org)
- Displacement of the ATP that binds to the JH2 pseudokinase domain allosterically disrupts TYK2 catalytic activity, in a mechanism that appears to stablise the kinase in an auto-inhibitory conformation. (guidetopharmacology.org)
- then this catalytic domain binds to and cleaves a nerve-cell protein, making it impossible for the nerve cell to "fire," or send signals. (bnl.gov)
- This study looked specifically at how the catalytic domain of one type of neurotoxin, neurotoxin F, recognizes and binds to its target nerve-cell protein to perform this final, paralyzing step," said Brookhaven Lab biologist Subramanyam Swaminathan, who led the research team. (bnl.gov)
Increase in intracellular2
- Cullen, 1997), suggesting that an increase in intracellular IP4 levels leads to the release of the PH domain from the membrane. (sdbonline.org)
- Activation of GC-C by these ligands results in an increase in intracellular cGMP levels, which then activates cGMP-dependent protein kinase and cross-activates protein kinase A. In turn, these activated kinases phosphorylate and active the cystic fibrosis transmembrane conductance regulator (CFTR), resulting in chloride and water secretion into the intestine lumen, thus regulating salt and water homeostasis in the intestine. (iisc.ac.in)
Residues3
- 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 surface area devoid of charged residues in the p75ICD death domain may indicate a potential site of interaction with downstream targets. (embl-heidelberg.de)
- Although the localisation of VEGFR-2 was independent of the catalytic and intracellular domain of MT1-MMP, intracellular signalling dependent on VEGFR-2 activity leading to VEGF-A transcription still required the MT1-MMP catalytic and intracellular domain, including residues Y573, C574 and DKV582. (uea.ac.uk)
Receptors4
- Various cytokines and their receptors mediate intracellular signalling through pairs of Janus kinase family enzymes. (guidetopharmacology.org)
- Current structural knowledge of the molecular system root catalytic activation of HER category of receptors. (bio-biz-navi.com)
- Recently, several novel agents targeting growth factor receptors, angiogenic pathways, adhesion molecules and mediators of intracellular signal transduction have been clinically explored. (docksci.com)
- In mammals, there are seven isoforms of receptors guanylyl cyclase, GC-A through GC-G. These recptors have a highly conseved modular domin organization with an N-terminal extracellular domain, a single transmembrane domain and a C- terminal intra cellular regions. (iisc.ac.in)
Signal transduction1
- Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. (lu.se)
Tyrosine kinase2
- Tyrosine kinase, catalytic domain. (unl.edu)
- Protein Tyrosine Kinase (PTK) family, catalytic domain. (unl.edu)
Guanylyl cyclase1
- The intracellular region contains a juxtamembrane domain followed by a protein-kinase domain, a linker region and a catalytic guanylyl cyclase domain. (iisc.ac.in)
Subfamily1
- Members of this subfamily contain PX and Pleckstrin Homology (PH) domains in addition to the catalytic domain. (nih.gov)
Activity12
- PLD activity has been detected in viruses, bacteria, yeast, plants, and mammals, but the PX domain is not present in PLDs from viruses and bacteria. (nih.gov)
- The Gap1 catalytic domain alone is insufficient for in vivo activity of Gap1, indicating a requirement for the additional domains. (sdbonline.org)
- An inositol-1,3,4,5-tetrakisphosphate (IP4)-sensitive extended PH domain is essential for Gap1 activity, while Ca2+-sensitive C2 domains and a glutamine-rich region contribute equally to full activity in vivo. (sdbonline.org)
- We discovered that MT1-MMP regulates VEGFR-2 cell surface localisation and forms a complex with VEGFR-2 and Src that is dependent on the MT1-MMP hemopexin domain and independent of its catalytic activity. (uea.ac.uk)
- However, there was redundancy in the function of the catalytic activity of MT1-MMP, as this could be substituted with MMP-2 or MMP-7 in cells expressing inactive MT1-MMP. (uea.ac.uk)
- however, it is devoid of enzymatic activity due to amino acid substitutions in the catalytic triad. (spandidos-publications.com)
- Both substitutions affect highly conserved amino acids located in the regulatory GAF-B domain, which, by binding to cAMP, stimulates the activity of the PDE10A catalytic domain. (northwestern.edu)
- In vitro functional studies showed that neither substitution affects the basal PDE10A activity, but they severely disrupt the stimulatory effect mediated by cAMP binding to the GAF-B domain. (northwestern.edu)
- To assess the importance of this carbohydrate-active enzyme in the feeding act of Orciraptor , we recombinantly produced its catalytic domain and studied the enzymatic activity, cellular localisation and function. (megazyme.com)
- Results: The GH5_5 catalytic domain from Orciraptor showed pronounced activity on soluble cellulose derivatives and mixed-linkage glucans, with reaction optima comparable to known GH5_5 representatives. (megazyme.com)
- Among the mAbs, there were significant differences in extraction efficiency, ability to extract BoNT/A subtypes, and inhibitory effect on BoNT catalytic activity. (cdc.gov)
- However, the biochemical basis for the combined enzyme deficiency is a loss of a protective protein that interacts with both enzymes to produce catalytic activity. (medscape.com)
Substrates1
- The structure exhibits an essentially 'closed' conformation of the domains which is similar to that of cAPK complexed with substrates. (ox.ac.uk)
Highly conserved1
- The primary sequences of ePK catalytic domains are highly conserved, indicating a common ancestry. (dissertation.com)
Eukaryotic2
Kinase domain1
- However, recent studies have suggested that BRAFi/MEKi and ERK1/2i resistance can arise through activation of a parallel signalling pathway leading to activation of ERK5, an unusual protein kinase that contains both a kinase domain and a transcriptional transactivation domain. (babraham.ac.uk)
Transmembrane V0 domain2
Subunit2
- Each subunit has a region called a motor domain (also known as its 'head') that can bind to the microtubule and to a molecule called ATP, which provides the energy required for the motor to step forward. (elifesciences.org)
- In the F-ATPase from Geobacillus stearothermophilus, conformational changes in the ε-subunit are influenced by intracellular ATP concentration and membrane potential. (rcsb.org)
Protein Tyrosine Ph1
- CD45 is a member of the Protein Tyrosine Phosphatase (PTP) family: its intracellular (COOH-terminal) region contains two PTP catalytic domains, and the extracellular region is highly variable due to alternative splicing of exons 4, 5, and 6 (designated A, B, and C, respectively), plus differing levels of glycosylation. (bdbiosciences.com)
ATPase1
- The crystal structure has been determined of the F1-catalytic domain of the F-ATPase from Caldalkalibacillus thermarum, which hydrolyzes adenosine triphosphate (ATP) poorly. (rcsb.org)
Granules2
- The preprohormone is activated via post-translational modification that involves cleavage of the 25 amino acid signal sequence to produce proANP, a 126 amino acid peptide that is the major form of ANP stored in intracellular granules of the atria. (wikipedia.org)
- Immunocytochemistry with a polyclonal antibody raised against the GH5_5 domain revealed that the native endocellulase localises to the contact zone of Orciraptor and the algal cell wall (= perforation zone) and to intracellular granules, which were enriched during attack. (megazyme.com)
Amino acid1
- Each predicted domain is represented by a colored rectangle with corresponding amino acid numbers shown below. (jneurosci.org)
Kinesin2
- This protein is a catalytic kinesin motor with coiled-coil and Smc domains. (biolegend.com)
- Kinesin motor, catalytic domain. (umbc.edu)
Dual-specificity2
- The catalytic domain of this dual-specificity phosphatase has recently been mapped to the 180 most C-terminal amino acids. (embl.de)
- It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. (ayassbioscience.com)
Mutations5
- The histograms below the weblogo indicate mutations found on the domain. (umbc.edu)
- To comprehend the consequences of cancer-associated HER3 mutations on the molecular level we resolved the buildings of two HER3 kinase mutants each within a heterodimeric complicated using the kinase domains of EGFR. (bio-biz-navi.com)
- Oddly enough the Meclofenoxate HCl missense mutations situated in the catalytically inactive HER3 kinase domains are the most powerful gain-of-function substitutions ( 19 ). (bio-biz-navi.com)
- This review summarizes the cellular function and pathophysiology of LRRK2 ROCO domain mutations in PD and the perspective of therapeutic approaches. (biomedcentral.com)
- Structure of the functional domain of the LRRK2 protein and the pathogenic mutations associated with PD. (biomedcentral.com)
PTKc1
- This PTKc family is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). (unl.edu)
RTKs1
- RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. (unl.edu)
Shown to bind phospholipids2
- The N-terminal C2a domain has been shown to bind phospholipids in a Ca2+-dependent manner (Fukuda, 1996 and Fukuda, 1997), while the role of the C2b domain remains unclear. (sdbonline.org)
- The C2 domain of this protein was shown to bind phospholipids but not Ca2+, which suggests that this enzyme may function in a calcium-independent manner. (utsouthwestern.edu)
Membrane2
- Upon prolonged high intracellular rises in Ca 2+ , platelets develop a procoagulant phenotype that is characterized by the surface membrane exposure of phosphatidylserine and by the inactivation of integrin α IIb β 3 (procoagulant platelet population) ( 5 ). (frontiersin.org)
- Fukuda, 1996), implying that release of the PH domain from the membrane is accompanied by activation of the catalytic domain. (sdbonline.org)
Segment1
- The polypeptide segment connecting the transmembrane and death domains as well as the serine/threonine-rich C-terminal end are highly flexible in p75ICD. (embl-heidelberg.de)
Structural2
- Most of the 10 exons coding the intracellular portion correspond to specific structural elements, such as α-helices or β-sheets. (creation.com)
- The discovery process of Akt inhibitors has evolved from adenosine triphosphate (ATP)‑competitive agents to alternative approaches employing allosteric sites in order to overcome the high degree of structural similarity between Akt isoforms in the catalytic domain, and considerable structural analogy to the AGC kinase family. (spandidos-publications.com)
Membranes1
- PLD1 is located mainly in intracellular membranes while PLD2 is associated with plasma membranes. (nih.gov)
Pathway2
- It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. (ayassbioscience.com)
- The process of cell death involves several signaling pathways, including the autophagic-lysosomal pathway, intracellular trafficking, mitochondrial dysfunction, and the ubiquitin-proteasome system. (biomedcentral.com)
Regulation1
- PDE10A contributes to the regulation of the intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). (northwestern.edu)
Enzyme2
- Furthermore, a strong positive genetic interaction occurs between Gap1 and phospholipase Cgamma (PLCgamma), an enzyme that generates inositol-1,4,5-trisphosphate, a precursor for IP4 and a second messenger for intracellular Ca2+ release. (sdbonline.org)
- Lysosomal enzyme tripeptidyl peptidase 1 destabilizes fibrillar Aβ by multiple endoproteolytic cleavages within the β-sheet domain. (uni-bielefeld.de)
Clostridium1
- The catalytic domain of Clostridium botulinum neurotoxin type F (represented as a molecular surface, gray) bound to an inhibitor molecule (colored ribbon) designed to mimic the nerve-cell protein the toxin cleaves. (bnl.gov)
Mechanism2
- By analyzing the single-molecule properties of engineered motors, we demonstrate that the non-catalytic domain has a key role in the motility mechanism by acting as a 'foothold' that allows Kar3 to bias translocation towards the minus end. (elifesciences.org)
- The assembly mechanism of the 19S domain is poorly understood, but Hsp90 is thought to play a role. (tocris.com)
Regulatory domains1
- Functional diversity between PTPases is endowed by regulatory domains and subunits. (embl.de)
Pathways2
- This review summarizes the intracellular functions of Akt as a pivotal point of converging signaling pathways involved in cell growth, proliferation, apoptotis and neo‑angiogenesis, and focuses on the drug design strategies to develop potent anticancer agents targeting Akt. (spandidos-publications.com)
- PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. (utsouthwestern.edu)
Region1
- when ATP is scarce, the α-helices are proposed to inhibit ATP hydrolysis by assuming an "up" state, where the α-helices, devoid of ATP, enter the α3β3-catalytic region. (rcsb.org)
Bind1
- They then allowed each to bind to the catalytic domain of the toxin, and analyzed the structures using high-intensity x-rays at Brookhaven's National Synchrotron Light Source (NSLS). (bnl.gov)
Structures1
- Two structures of the catalytic domain of phosphorylase kinase: an active protein kinase complexed with substrate analogue and product. (ox.ac.uk)
Concentrations1
Bacteria1
- Lateral phage transfer in obligate intracellular bacteria (wolbachia): verification from natural populations. (mbl.edu)
Molecule3
- However, although the βE-catalytic site is in the usual "open" conformation, it is occupied by the unique combination of an ADP molecule with no magnesium ion and a phosphate ion. (rcsb.org)
- Apart from the catalytic domain in the middle of the molecule, all Gap1 family members share two N-terminal C2 domains and a C-terminal extended PH domain. (sdbonline.org)
- One possibility would be to add a transmembrane sequence or some other means of intracellular transport to the inhibitor molecule. (bnl.gov)
Conformation1
- The phosphorylated residue that is located at the domain interface in many protein kinases and that is believed to stabilize an active conformation is substituted by a glutamate in Phk gamma trnc. (ox.ac.uk)
Function3
- The second class shows a release of evolutionary constraint for the sites around the catalytic centre, which emphasises a difference in function from the first group. (embl.de)
- However, the physiological relevance of any of these domains for Gap1 in vivo function has not been established. (sdbonline.org)
- Gap1 transgenes containing only the catalytic domain ( sevGapM ) fail to rescue either the partial or complete loss-of-function phenotype of Gap1 . (sdbonline.org)
Organelles1
- Microtubule-dependent molecular motors that play important roles in intracellular transport of organelles and in cell division. (umbc.edu)