• In addition, we performed a detailed structural and functional study of this domain in which we identified key residues required for its activity. (ox.ac.uk)
  • We discuss structural features that produce this novel binding motif, including the role of the CaMBD peptide residues Arg-408, Val-409, and Phe-410, which work to provide rigidity to the otherwise flexible central CaM helix joining the N- and C-lobes, ultimately keeping these lobes apart and forcing "head-to-tail" dimerization to attain the requisite N- and C-lobe pairing for CaMBD binding. (rcsb.org)
  • With the conserved Zn(2+)-binding motifs HEXXH and NEXFA as well as the N-terminal substrate-anchoring glutamate residues, F3 together with the leukotriene A4 hydrolase, represents a novel gluzincin subfamily of aminoproteases. (rcsb.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)
  • There are no totally invariant residues within the PH domain. (embl.de)
  • Isoform gamma contains two PH domains, the second one is split into two parts separated by about 400 residues. (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)
  • These 55 kDa proteins have highly diverse N-terminal regions (approximately residues 1-90) but conserved catalytic domains (approximately from residue 91 to the C-termini). (elsevierpure.com)
  • The mTORC1 (3.0 Å) and RHEB-mTORC1 (3.4 Å) structures showed that RHEB bound mTOR away from the active kinase site and caused a global conformational change (including conformation changes within the FAT domain) that realigned the active site residues for an allosteric catalytic acceleration, providing a structural mechanism by which RHEB activates mTORC1. (aacrjournals.org)
  • The method, named Predikin, identifies key conserved substrate-determining residues in the kinase catalytic domain that contact the substrate in the region of the phosphorylation site and so determine the sequence surrounding the phosphorylation site. (biomedcentral.com)
  • The second factor, termed peptide specificity, describes the interaction between amino acid residues in the catalytic domain of the protein kinase and the substrate residues that surround the phosphorylated residue. (biomedcentral.com)
  • Crystal structures of protein kinases with bound substrate peptides show that substrate residues at positions -3 to +3 relative to the phosphorylated serine, threonine or tyrosine residue adopt an extended conformation and bind to a pocket in the catalytic domain of the protein kinase [ 8 ]. (biomedcentral.com)
  • The heptapeptide sequence from -3 to +3 that best binds to the pocket is determined by the physicochemical nature of the residues in the catalytic domain that line the pocket and contact the substrate. (biomedcentral.com)
  • Catalytically active TR mART domains hallmark catalytic residues in the active site. (expasy.org)
  • A deep pocket with a narrow entrance between the two domains, containing strictly conserved residues primarily contributed by the catalytic domain, is identified as a potential 3-dehydroshikimate binding pocket. (ox.ac.uk)
  • The selectivity of an individual SH2 domain is not sharply defined, and a range of residues is typically tolerated at each site following the phosphotyrosine. (lu.se)
  • It contains one GTPase binding domain (aa 75-105) plus a protein kinase catalytic region (aa 250-521). (rndsystems.com)
  • Although the role of modular protein-protein interaction domains in kinase and phosphatase signaling has been well characterized, it is becoming clear that many kinases and phosphatases utilize docking interactions - recognition of a short peptide motif in target partners by a groove on the catalytic domain that is separate from the active site. (nih.gov)
  • Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. (embl.de)
  • Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. (embl.de)
  • Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase. (umbc.edu)
  • Serine/threonine kinases (STKs), p21-activated kinase (PAK) subfamily, catalytic (c) domain. (umbc.edu)
  • The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. (umbc.edu)
  • 1998). The Src SH2 domain has been shown to bind a phosphorylated tyrosine at the C-terminus of the same molecule resulting inactivation of enzyme activity by rearrangement of catalytic center in the kinase domain (reviewed in Hubbard et al. (lu.se)
  • Pol δ is anchored to one of the three PCNA monomers through the C-terminal domain of the catalytic subunit. (nature.com)
  • Mammalian Pol δ consists of a catalytic subunit and three regulatory subunits (Fig. 1a ). (nature.com)
  • The catalytic subunit (p125) harbours the polymerase and exonuclease activities, and a metal-binding C-terminal domain (CTD). (nature.com)
  • The activity of the protein phosphatase calcineurin (CN) is regulated by an autoinhibition mechanism wherein several domains from its catalytic A subunit, including the calmodulin binding domain (CaMBD), block access to its active site. (rcsb.org)
  • 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)
  • OXR1 contains the Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic (TLDc) domain, a motif present in a family of proteins including TBC1 domain family member 24 (TBC1D24), a protein mutated in a range of disorders characterized by seizures, hearing loss, and neurodegeneration. (ox.ac.uk)
  • To understand the role of this domain in the stress response, we carried out systematic analysis of all mammalian TLDc domain-containing proteins, investigating their expression and neuroprotective properties in parallel. (ox.ac.uk)
  • Our data demonstrate that the integrity of the TLDc domain is essential for conferring neuroprotection, an important step in understanding the functional significance of all TLDc domain-containing proteins in the cellular stress response and disease. (ox.ac.uk)
  • TIM barrels appear to have evolved through gene duplication and domain fusion events of half-barrel proteins, with a majority of TIM barrels originating from a common ancestor. (wikipedia.org)
  • Successful TIM barrel designs include both domain fusions of existing proteins and de novo designs. (wikipedia.org)
  • 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)
  • Domain commonly found in eukaryotic signalling proteins. (embl.de)
  • The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. (embl.de)
  • Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. (embl.de)
  • Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways. (embl.de)
  • Pleckstrin is one of the rare proteins to contains two PH domains. (embl.de)
  • Regulators of small G-proteins like guanine nucleotide releasing factor GNRP (Ras-GRF) (which contains 2 PH domains), guanine nucleotide exchange proteins like vav, dbl, SoS and Saccharomyces cerevisiae CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr. (embl.de)
  • Cytoskeletal proteins such as dynamin (see IPR001401 ), Caenorhabditis elegans kinesin-like protein unc-104 (see IPR001752 ), spectrin beta-chain, syntrophin (2 PH domains) and S. cerevisiae nuclear migration protein NUM1. (embl.de)
  • There are 196127 PH domains in 171590 proteins in SMART's nrdb database. (embl.de)
  • PAWS1 is a member of the poorly characterised FAM83 family of proteins that are linked through the conserved DUF1669 domain of unknown function, which possesses a pseudo-Phospholipase D catalytic motif. (dundee.ac.uk)
  • We aim to understand how the DUF1669 domain controls the function of the FAM83 family of proteins in their potentially diverse cellular roles. (dundee.ac.uk)
  • 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)
  • The HAD domain-containing proteins catalyze hydrolase or phosphohydrolase reactions. (aocs.org)
  • This domain occurred 446 times on human genes ( 1027 proteins). (umbc.edu)
  • Tyrosine phosphorylated regions in proteins function as specific binding sites for the SH2 domains containing cellular signalling proteins. (lu.se)
  • In this system, the endonuclease Cas9 generates double strand breaks in DNA upon RNA-guided recognition of a complementary DNA sequence, which strictly requires the presence of a protospacer adjacent motif (PAM) next to the target site. (nih.gov)
  • Following crRNA and tracrRNA hybridization, SpCas9 is targeted to genomic loci matching a 20-nt guide sequence within the crRNA, immediately upstream of a required 5′-NGG protospacer adjacent motif (PAM) 11 . (cdc.gov)
  • a Domain organization of the four subunits of human Pol δ and amino acid sequence of PCNA-interacting (PIP-box) motifs. (nature.com)
  • The PAP activities of the lipins depend on a conserved C-terminus domain with sequence homology to the haloacid dehalogenase or HAD-like domain [1]. (aocs.org)
  • The DxDxT catalytic motif is present in all HAD-like domains, along with a characteristic and conserved sequence of α-helices and β-sheets [3]. (aocs.org)
  • RAPTOR binds to a TOR signaling sequence (TOS) motif in substrates including the S6K1 substrate, which had previously been suggested to be recruited by the mTOR FRB domain. (aacrjournals.org)
  • The enzyme contains a unique glycine-rich P-loop with a conserved sequence motif, GAGGXX, that results in NADPH adopting a nonstandard binding mode with the nicotinamide and ribose moieties disordered in the binary complex. (ox.ac.uk)
  • 1993). Based on these results, together with structural analyses of different ligand-binding models, it is apparent that SH2 domains bind distinct but overlapping sequence motifs. (lu.se)
  • 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)
  • It has two domains, one that binds protective antigen and another that has ADP-ribosyltransferase activity [ 5 ]. (expasy.org)
  • A loop from the N-terminal SH2 domain binds to the catalytic cleft of the phosphatase domain in the same SHP-2 molecule leading to an autoinhibited configuration (Hof et al. (lu.se)
  • 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)
  • We discuss the functional implications of these structures with respect to the underlying catalytic mechanism, substrate recognition and processing, and possible component interactions. (rcsb.org)
  • This arrangement allows PCNA to thread and stabilize the DNA exiting the catalytic cleft and recruit FEN1 to one unoccupied monomer in a toolbelt fashion. (nature.com)
  • Structural inserts ranging from extended loops to independent protein domains may be inserted in place of these loops or at the N-terminus/C-terminals. (wikipedia.org)
  • All TIM barrel enzymes possess catalytic sites at the C-terminal end of the β-barrel, and structural inserts present close to this end may aid in catalytic activity. (wikipedia.org)
  • This revealed the active site of this ribozyme to contain two catalytic metal ions coordinated by a conserved RNA structural motif called domain 5. (ucsd.edu)
  • Crystal structure and novel recognition motif of rho ADP-ribosylating C3 exoenzyme from Clostridium botulinum: structural insights for recognition specificity and catalysis. (expasy.org)
  • Toor N, Robart AR, Christianson J, Zimmerly S, "Self-splicing of a group IIC intron: 5' exon recognition and alternative 5' splicing events implicate the stem-loop motif of a transcriptional terminator. (ucsd.edu)
  • 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)
  • In order to determine the acyltransferases responsible for the modification of Spike, researchers have individually depleted the 23 conserved zinc-finger domains with a DHHC motif in their catalytic sites (ZDHHCs) by RNA interference in Hela cells. (news-medical.net)
  • All five members of this family (SMYD1-5) contain a conserved catalytic SET domain and a zinc-finger MYND motif. (thesgc.org)
  • Determination of the 1.75 Å FRB-S6K1 crystal structure confirmed that the FRB domain is a substrate recruitment site. (aacrjournals.org)
  • The RAPTOR-PRAS40 (3.35 Å) structure revealed that PRAS40 blocked the mTOR FKBP12-rapamycin-binding (FRB) substrate-recruitment site as well as RAPTOR binding to the TOS motif. (aacrjournals.org)
  • A model of Cdc25 phosphatase catalytic domain and Cdk-interaction surface based on the presence of a rhodanese homology domain. (embl.de)
  • The catalytic domain of this dual-specificity phosphatase has recently been mapped to the 180 most C-terminal amino acids. (embl.de)
  • The TLDc domain is highly conserved across species, although the structure-function relationship is unknown. (ox.ac.uk)
  • No pairwise interactions are available for this conserved domain. (umbc.edu)
  • In addition to their role in assembling activated complexes, particular SH2 domains also form intramolecular interactions that regulate enzyme activity. (lu.se)
  • 1998). In both examples, the high affinity ligands can compete with the intramolecular interactions and release the catalytic domains for their in vivo targets. (lu.se)
  • Upon binding of Ca2+ and calmodulin (Ca2+/CaM) to CaMBD, the autoinhibitory domains dissociate from the catalytic groove, thus activating the enzyme. (rcsb.org)
  • Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). (umbc.edu)
  • 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)
  • The molecule contains two domains, a catalytic domain with a novel open twisted α/β motif and an NADPH binding domain with a typical Rossmann fold. (ox.ac.uk)
  • XopAI uses an altered mART domain to bind its own N-terminal peptide containing a conserved Arg residue [ 8 ]. (expasy.org)
  • Structures of a significant number of SH2 domains both in isolation and bound to various target molecules have been determined by X-ray crystallography and NMR spectroscopy. (lu.se)
  • A) Structure superposition of the modeled structure of YycG HATPase_c domain of S. epidermidis (blue) with the NMR structure of the homologous domain of EnvZ in E. coli (yellow). (biomedcentral.com)
  • Functional diversity between PTPases is endowed by regulatory domains and subunits. (embl.de)
  • The mART domain adopts a mixed α/β-fold with a characteristic β-sandwich structure. (expasy.org)
  • TRID is a distinct gene product with an extracellular TRAIL-binding domain and a transmembrane domain but no intracellular signaling domain. (embl-heidelberg.de)
  • The co-transcriptional regulatory binding site on the lipins is a conserved LxxIL motif, which is distinct from the active site. (aocs.org)
  • Finally, we present a new mouse insertional mutant of Oxr1, confirming that specific disruption of the TLDc domain in vivo is sufficient to cause neurodegeneration. (ox.ac.uk)
  • 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)
  • However, the physiological relevance of any of these domains for Gap1 in vivo function has not been established. (sdbonline.org)
  • Binding of SH2 domains to their in vivo targets recruits the SH2 domain-containing protein to its proper signalling complex and thereby initiates or regulates downstream signalling cascades (reviewed in Schlessinger and Lemmon, 2003). (lu.se)
  • Supporting these findings, different SH2 domains have been shown to compete for same binding target in vivo (e.g. (lu.se)
  • 1.Brown MA, Sims RJ 3rd, Gottlieb PD, Tucker PW (2006) Identification and characterization of Smyd2: a split SET/MYND domain-containing histone H3 lysine 36-specific methyltransferase that interacts with the Sin3 histone deacetylase complex . (thesgc.org)
  • Each predicted domain is represented by a colored rectangle with corresponding amino acid numbers shown below. (jneurosci.org)
  • 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)
  • PAM acts as an allosteric effector and triggers the interdependent conformational dynamics of the Cas9 catalytic domains (HNH and RuvC), responsible for concerted cleavage of the two DNA strands. (nih.gov)
  • 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)
  • Nearly the entire pool of PI4KIIα behaves as an integral membrane protein, in spite of a lack of a transmembrane domain. (elsevierpure.com)
  • Four high conserved motifs, N-box (Asn499~Tyr507), G1-box (Ile53~Ile538), F-box (Asp544~Phe547), G2-box (Gly563~Gly567), around the catalytic domain of the HPK encompasses the active ATP-binding pocket and a long loop from Asp548 to Ala574 drifts outside the pocket. (biomedcentral.com)
  • The latter enzyme, called Sc LPMO10D, and most of the enzymes found in this subclade are unique, not only because of variation in the catalytic domain, but also as their C-terminus contains a cell wall sorting signal (CWSS), which flags the LPMO for covalent anchoring to the cell wall. (nature.com)
  • The cytoplasmic region generally contains two copies of the PTPase domain. (embl.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)
  • Conserved motif and gene structure analysis revealed high levels of conservation within and between phylogenetic subfamilies. (figshare.com)
  • Loops at the C-terminal ends of the β-barrel are responsible for catalytic activity while N-terminal end loops are important for the stability of the TIM-barrels. (wikipedia.org)
  • Tissue inhibitors of matrix metallo-proteinases (TIMPs) are known to have the ability to inhibit the catalytic activity of MMPs. (biomedcentral.com)
  • 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)
  • NMR structure of the death domain of the p75 neurotrophin receptor. (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)
  • 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)
  • and an alpha-helical C-terminal domain, the latter forming a deep cavity at the active site. (rcsb.org)
  • This entry represents the PTPase domain found in several tyrosine-specific protein phosphatases (PTPases). (embl.de)
  • The inactive domains of tandem phosphatases can be divided into two classes. (embl.de)
  • The death domain of p75ICD consists of two perpendicular sets of three helices packed into a globular structure. (embl-heidelberg.de)
  • N-glycosylation, also occur on their luminal domains and S-acylation on the cytosolic domains. (news-medical.net)
  • We aim to assign the biochemical role to this domain, through proteomic, biochemical, cellular and biophysical approaches. (dundee.ac.uk)
  • The catalytic core sits on top of PCNA in an open configuration while the regulatory subunits project laterally. (nature.com)
  • This integral association with membranes is due to palmitoylation of a cysteine-rich motif, CCPCC, located within the catalytic domain. (elsevierpure.com)
  • Although the CCPCC motif is conserved in PI4KIIβ, only 50 % of PI4KIIβ is membrane-associated, and approximately half of this pool is only peripherally attached to the membranes. (elsevierpure.com)
  • There are five SH3-binding motifs. (rndsystems.com)
  • CTD C-terminal domain, OB oligonucleotide binding domain, PDE phosphodiesterase domain. (nature.com)
  • This structure revealed a novel CaM binding motif. (rcsb.org)
  • Thus, it validates the existence of this novel CaM binding motif. (rcsb.org)
  • Some enzymatically inactive mART domains, for example, the N-terminal domains of C2 and VIP2 toxins, have acquired a new, protein-binding function. (expasy.org)
  • Domain fusions experiments have resulted in many successful designs, whereas de novo designs only yielded successes after 28 years of incremental development. (wikipedia.org)
  • Cullen, 1997), suggesting that an increase in intracellular IP4 levels leads to the release of the PH domain from the membrane. (sdbonline.org)
  • Chan RT, Robart AR, Rajashankar KR, Pyle AM, Toor N, "Crystal structure of a group II intron in the pre-catalytic state. (ucsd.edu)
  • Keating KS, Toor N, Pyle AM, "The GANC tetraloop: a novel motif in the group IIC intron structure. (ucsd.edu)
  • The modeled structure of the YycG HATPase_c domain of S. epidermidis . (biomedcentral.com)
  • B) The solid ribbon representation of the structure model of the YycG HATPase_c domain. (biomedcentral.com)
  • The YycG HATPase_c domain of S. epidermidis folds into a two-layer sandwich structure. (biomedcentral.com)
  • SET and MYND domain-containing protein 2 (SMYD2) is a member of the SMYD family of protein methyltransferases. (thesgc.org)
  • A third protease, α-secretase, cuts APP within the Aβ domain, thus precluding Aβ formation. (jneurosci.org)