Domains phosphotyrosine. Medical search. Frequent questions

Unexpectedly, the interaction between DLC-1 and the cten SH2 domain is independent of tyrosine phosphorylation of DLC-1. (rupress.org)
BTK, a TEC-family tyrosine kinase activated by the B-cell antigen receptor, contains a variety of regulatory domains and it is subject to complex regulation by membrane phospholipids, protein ligands, phosphorylation, and dimerization. (elifesciences.org)
On binding of insulinlike growth factors to the receptor, adaptor proteins, such as insulin-receptor substrate-1 (IRS-1) and IRS-2, are recruited to the phosphorylation site of the cytoplasmic domain ( 19 - 21 ). (snmjournals.org)
Subsequent studies have shown that, while binding of SH2 domains to their target proteins is strictly regulated by tyrosine phosphorylation, most PTB domains actually bind to their (nonphosphorylated) targets constitutively. (chemdiv.com)
Upon tyrosine phosphorylation, insulin receptor substrate proteins interact with specific SH2 DOMAIN containing proteins that are involved in insulin receptor signaling. (bvsalud.org)

Tensin is a multi-domain protein that binds to actin filaments and functions as a focal-adhesion molecule (focal adhesions are regions of plasma membrane through which cells attach to the extracellular matrix). (wikipedia.org)
We report that cten binds to another tumor suppressor, deleted in liver cancer 1 (DLC-1), and the SH2 domain of cten is responsible for the interaction. (rupress.org)
The Tir protein of EPEC binds NCK1/NCK2 SH2 domains through a high affinity pYDEV motif ( Frese,2006 ). (eu.org)
In the proposed "zinc finger" DNA-binding motif, each repeat unit binds a zinc metal ion through invariant Cys and His residues and this drives the folding of each 30-residue unit into an independent nucleic acid-binding domain. (embl.de)
The chromo-domain binds histone H3 tails methylated on lysine 9. (cipsm.de)
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)

The PTB domain interacts with the cytoplasmic tails of beta integrin by binding to an NPXY motif. (wikipedia.org)
Numb-associated kinase interacts with the phosphotyrosine binding domain of Numb and antagonizes the function of Numb in vivo. (sdbonline.org)
The proteins share an N-terminal PLECKSTRIN HOMOLOGY DOMAIN, a phosphotyrosine-binding domain that interacts with the phosphorylated INSULIN RECEPTOR, and a C-terminal TYROSINE-rich domain. (bvsalud.org)

AFAP1L1 intersects several invadopodia pathway components through its multiple domains and motifs, including the following (i) pleckstrin homology domains that bind phospholipids generated at the plasma membrane by phosphoinositide 3-kinase, (ii) a direct filamentous-actin binding domain and (iii) phospho-tyrosine motifs (pY136 and pY566) that specifically bind Vav2 and Nck2 SH2 domains, respectively. (nature.com)
These phosphotyrosine motifs are essential for AFAP1L1-mediated cytoskeleton regulation. (nature.com)
Several different binding motifs are known, for example: pYEEI (Src-family SH2 domains), pY [IV]. (eu.org)
The C-terminal half of the SH2 domain exhibits greater structural variability and provides a platform for accommodating different kinds of SH2-binding motifs. (eu.org)
Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. (embl-heidelberg.de)
It does not share significant sequence homology with other subtypes of small G-protein GEF motifs such as the Cdc25 domain and the Sec7 domain, which specifically interact with Ras and ARF family small GTPases, respectively, nor with other Rho protein interactive motifs, indicating that the Dbl family proteins are evolutionarily unique. (embl-heidelberg.de)
The CCM2 phosphotyrosine binding (PTB) domain is necessary for a canonical interaction with NPxY motifs within CCM1. (unc.edu)
It contains one PH (pleckstrin homology) domain (aa 16-144), followed by a PTB (phosphotyrosine-binding)domain (aa 194-298) and seven YxxM (Tyr/x/x/Met) motifs (aa 540-1075). (rndsystems.com)
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)

Two arginines in this domain are responsible for hydrogen bonding phosphotyrosine residues on an Ac-LYASSNPApY-NH2 peptide in the juxtamembrane region of the insulin receptor. (wikipedia.org)
Different families of SH2 domains may have different binding specificity, which is usually determined by a few residues C-terminal with respect to the pY (positions +1 to +4). (eu.org)
The residue at pY+2 does not make direct side chain interactions with the SH2 domain, but aromatic residues are not allowed. (eu.org)
Positively charged residues are disfavoured at pY-1 and pY-2 due to the positively charged SH2 domain surface, but are tolerated when pY+1 and pY+3 are strong residues. (eu.org)
The proteins encoded by members of the Dbl family share a common domain, presented in this entry, of about 200 residues (designated the Dbl homology or DH domain) that has been shown to encode a GEF activity specific for a number of Rho family members. (embl-heidelberg.de)
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)
Residues from αB-helix and the EF and BG-loops are involved in binding of side chains C-terminal to phosphotyrosine in the ligand. (lu.se)

Structural basis for phosphotyrosine recognition by the Src homology-2 domains of the adapter proteins SH2-B and APS. (genscript.com)
This PTP contains two tandem Src homology-2 domains, which function as phospho-tyrosine binding domains and mediate the interaction of this PTP with its substrates. (antikoerper-online.de)

SH2 domains are phosphotyrosine recognition domains, often mediating transient interactions with target proteins. (eu.org)
Our results suggest that a screening approach using protein crystallography is particularly useful to identify universal fragments for the conserved hydrophilic recognition sites found in target families such as SH2 domains, phosphatases, kinases, proteases, and esterases. (rcsb.org)
Multiple modes of peptide recognition by the PTB domain of the cell fate determinant Numb. (sdbonline.org)

Together, these data provide the first structural elucidation of full-length BTK and allow a deeper understanding of allosteric control over the BTK kinase domain during distinct stages of activation. (elifesciences.org)
To obtain structural information, we synthesized single and double zinc finger peptides from the yeast transcription activator ADR1, and assessed the metal-binding and DNA-binding properties of these peptides, as well as the solution structure of the metal-stabilized domains, with the use of a variety of spectroscopic techniques. (embl.de)
The PH domain is invariably located immediately C-terminal to the DH domain and this invariant topography suggests a functional interdependence between these two structural modules. (embl-heidelberg.de)
Furthermore, structural analysis of particular TM domains suggested locations for phenoxybenzamine covalent interactions. (pharmacology2000.com)

Receptor dimerization and autophosphorylation attracts proteins containing Src homology 2 (SH2) or phosphotyrosine binding (PTB) domains including adaptor proteins like FRS2 and GRB2. (springer.com)
The VEE is a heterogeneous compartment containing the Adaptor Protein Phosphotyrosine Interacting with Pleckstrin homology Domain and Leucine Zipper 1 (APPL1) with distinct functions in regulating endosomal Gαs/cAMP signaling and rapid recycling. (frontiersin.org)

The human NCK1 (Nckα) and NCK2 (Nckβ/GRB4) SH2 domains show a degree of partner specificity but share the same mode of ligand binding ( Frese,2006 ) and belong to the class IA family which contains an aromatic residue (Phe) at the specificity-determining βD5 position ( Kaneko,2010 ). (eu.org)
The binding affinity of an SH2 domain to a pTyr containing ligand is moderate, with the typical affinity range between 0.1 µМ to 10 µМ for equilibrium dissociation constant values (Kd) ( Kaneko,2012 ). (eu.org)
The spacing of the cysteines in such a domain is C-x(2)-C-x(9 to 39)-C-x(1 to 3)-H-x(2 to 3)-C-x(2)-C-x(4 to 48)-C-x(2)-C. Metal ligand pairs one and three co-ordinate to bind one zinc ion, whilst pairs two and four bind the second. (embl-heidelberg.de)
The α-adrenergic receptor is described by seven α-helical transmembrane (TM) domains which form a 'crevice' for ligand binding. (pharmacology2000.com)

The 3D structure of the zinc ligation system is unique to the RING domain and is referred to as the 'cross-brace' motif. (embl-heidelberg.de)

On the way to activation, disassembly of the SH3-SH2- kinase core opens a new autoinhibitory site on the kinase domain for PHTH domain binding that is ultimately released upon interaction of PHTH with PIP3. (elifesciences.org)
Membrane-induced dimerization activates BTK and we present here a crystal structure of an activation loop swapped BTK kinase domain dimer that likely represents the conformational state leading to trans-autophosphorylation. (elifesciences.org)
The TEC and SRC kinases share the SH3-SH2-kinase domain arrangement (the 'Src module') ( Fig. 1a ). (elifesciences.org)
Structures of the autoinhibited SRC family kinases were solved in 1997 revealing, for the first time, the compact arrangement of the SH3 and SH2 domains assembled onto the distal side of the catalytic kinase domain [ 4 ]. (elifesciences.org)
Was this a function of differences in receptor primary sequence, their locations in the cell, or, possibly, the specificity of the protein kinase domain of the receptor? (the-scientist.com)
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)

Non-phosphorylated peptides do not bind to the SH2 domains. (eu.org)
Adam Kashishian (Fred Hutchinson Cancer Research Center, Seattle): "The question of the specificity of Src homology 2 (SH2) domain/phosphotyrosine interactions has been an important one since the ability of the SH2 domains to bind phosphotyrosine- containing peptides was first shown. (the-scientist.com)
The protease not only releases small peptides, such as the amyloid-β peptide, which drives Alzheimer's disease pathogenesis, but also intracellular domains, which can have critical functions in nuclear signaling. (cipsm.de)

The phosphotyrosine-binding domain (PTB, also phosphotyrosine-interaction or PI domain) in the protein tensin tends to be found at the C-terminus. (wikipedia.org)
Human tensin has actin-binding sites, an SH2 (Pfam PF00017) domain and a region similar to the tumour suppressor PTEN. (wikipedia.org)
The phosphotyrosine-binding domain of insulin receptor substrate-1 is not related to the phosphotyrosine-binding domain of tensin. (wikipedia.org)
The tensin family member cten (C-terminal tensin like) is an Src homology 2 (SH2) and phosphotyrosine binding domain-containing focal adhesion molecule that may function as a tumor suppressor. (rupress.org)

In molecular biology, Phosphotyrosine-binding domains are protein domains which bind to phosphotyrosine. (wikipedia.org)
TLN2 SH2 domains also bind phosphorylated tyrosines McCleverty CJ, Lin DC, Liddington RC (June 2007). (wikipedia.org)
The ECM proteins bind to the extracellular domains of integrin heterodimers, whereas the actin stress fibers link to integrin cytoplasmic tails via large molecular complexes. (rupress.org)
Different growth factor receptors were known to bind different constellations of SH2 domain-containing proteins. (the-scientist.com)

Insulin receptor substrate-1 proteins contain both a pleckstrin homology domain and a phosphotyrosine binding (PTB) domain. (wikipedia.org)
Precisely how the BTK N-terminal domains (the Pleckstrin homology/Tec homology (PHTH) domain and proline-rich regions (PRR) contain linker) contribute to BTK regulation remains unclear. (elifesciences.org)
Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin homology domain of protein kinase B induces a conformational change. (cathdb.info)

Three loops surround the peptide binding pocket and are important for specificity: Because these loops can be flexible, considerable variation in peptide binding can apply for any given SH2 domain. (eu.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)

The RING domain is a protein interaction domain that has been implicated in a range of diverse biological processes. (embl-heidelberg.de)

c) Structure of the BTK PHTH domain bound to IP4 (PDB: 1B55) [ 8 ]. (elifesciences.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)

The cytoplasmic portion contains two phospho-tyrosine-phosphatase domains. (beckman.com)
The screen for new phospho-tyrosine mimics binding to the SH2 domain of (pp60)src was initiated because of the limited cell penetration of phosphates. (rcsb.org)

In NCK SH2 domains, the EF loop is positioned away from the BG loop, exposing the pY+3 binding pocket where the side chain of Val forms tight interactions. (eu.org)
SH2 (Src homology region 2) and PTB (phosphotyrosine-binding) domains are small protein modules that mediate protein-protein interactions involved in many signal transduction pathways. (chemdiv.com)
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)

Phosphotyrosine acts as a docking site in protein regulation by stimulating interaction between tyrosine-phosphorylated proteins and phosphotyrosine domains of other proteins. (sigmaaldrich.com)
Biochemical data have established the role of the conserved DH domain in Rho GTPase interaction and activation, and the role of the tandem PH domain in intracellular targeting and/or regulation of DH domain function. (embl-heidelberg.de)

The PTB domains facilitate interaction with the activated tyrosine-phosphorylated insulin receptor. (wikipedia.org)

The DH domain of Dbl has been shown to mediate oligomerisation that is mostly homophilic in nature. (embl-heidelberg.de)

These proteins contain two related domains known as the chromo- and the chromoshadow-domain. (cipsm.de)

Linker regions and domains are labeled, residue numbering shows BTK domain boundaries. (elifesciences.org)
For example, if a particular cysteine residue located in the TM3 domain was changed to valine (by mutation), the receptor becomes resistant to phenoxybenzamine inactivation. (pharmacology2000.com)

Znf domains are often found in clusters, where fingers can have different binding specificities. (embl-heidelberg.de)

This entry represents RING-type zinc finger domains. (embl-heidelberg.de)
This entry represents the classical C2H2 zinc finger domain. (embl.de)

Click on the protein counts, or double click on taxonomic names to display all proteins containing RING domain in the selected taxonomic class. (embl-heidelberg.de)

Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. (embl-heidelberg.de)
5 ]. The three domains (SH3, SH2, kinase), the SH2-kinase linker, the activation loop and the active site are labeled. (elifesciences.org)

Both domains were initially identified as modules that recognize phosphorylated tyrosines in receptor tyrosine kinases and other signaling proteins. (chemdiv.com)
Las proteínas comparten un DOMINIO DE HOMOLOGÍA PLECKSTRIN, un dominio de unión a fosfotirosina que interacciona con el RECEPTOR DE INSULINA fosforilado y un dominio C-terminal rico en TIROSINA. (bvsalud.org)
Tras la fosforilación de la tirosina, las proteínas sustrato del receptor de insulina interaccionan con proteínas específicas que contienen el DOMINIO SH2 y que participan en la señalización del receptor de insulina. (bvsalud.org)

Trio and its homologue UNC-73 are unique within the Dbl family insomuch as they encode two distinct DH/PH domain modules. (embl-heidelberg.de)

Mutations identified in many SH2 domain-containing proteins as well as the SH2 domain itself are associated with human diseases ranging from cancers, diabetes, to immunodeficiencies. (eu.org)

The functions of SH2 and PTB domains include targeting of their host proteins to different cellular compartments, assembly of key components of signaling pathways in response to extracellular signals, and the control of autoinhibition, activation and dimerization of their host proteins. (chemdiv.com)
As the main component, extracellular structure contains some cysteine-rich repeats domains marked as D1-D2-D3 in GFRα1-3, and D2-D3 in GFRα4 ( Figure 1 a ). (medsci.org)

From studies of APP trafficking and metabolism, the following pathways have emerged: in the first, a fraction of APP molecules residing on the cell surface are processed by ADAM/TACE "sheddases" N-terminal to the ectodomain-transmembrane domain to generate an 83 aa membrane-tethered stub, termed α-CTF. (jneurosci.org)
alternatively, APP molecules that are subject to endocytosis are proteolyzed by BACE1 at a site further N-terminal to the membrane domain to generate a 99 aa membrane-tethered stub, termed β-CTF. (jneurosci.org)
Through a novel CCM2 PTB domain - Smurf1 HECT domain interaction, CCM2 recruits Smurf1 to specific locations at the plasma membrane where it specifically degrades RhoA. (unc.edu)

CryoEM reconstructions support conformational heterogeneity in the PHTH-PRR region wherein the globular PHTH domain adopts a range of states arrayed around the autoinhibited SH3-SH2-kinase core. (elifesciences.org)

Tyrosine phosphorylated regions in proteins function as specific binding sites for the SH2 domains containing cellular signalling proteins. (lu.se)

The Src Homology 2 (SH2) domain is a major protein interaction module that is central to tyrosine kinase signaling. (eu.org)

that is, of the 182 amino acids defining the TM domains of the human α 2A -adrenergic receptors, about 40% are identical with the human β 2 -adrenergic receptors. (pharmacology2000.com)

the E-value for the ZnF_C2H2 domain shown below is 1.92e-2. (embl.de)
the E-value for the ZnF_C2H2 domain shown below is 1.28e-3. (embl.de)
Supporting these findings, different SH2 domains have been shown to compete for same binding target in vivo (e.g. (lu.se)

All the analysed SH2 domains have a typical SH2 domain fold consisting of a large anti-parallel β-sheet sandwiched between two α-helices The central β-sheet divides the domain into two functionally separate sides. (lu.se)

Here we report the selection of camelid-derived single-domain antibodies (nanobodies) that modulate the conformation and spectral properties of the green fluorescent protein (GFP). (cipsm.de)

Anatomy20

Organisms11

Diseases2

Chemicals and Drugs128

Analytical, Diagnostic and Therapeutic Techniques and Equipment31

Phenomena and Processes61

Information Science4

Health Care1

Phosphorylation5

Binds6

Interacts3

Motifs9

Residues7

Homology-2 domains2

Recognition3

Structural4

Adaptor2

Ligand4

Motif1

Kinase domain6

Peptides3

Tensin4

Bind4

Pleckstrin homology3

Peptide1

Regulates1

Interaction domain1

Bound2

Phospho-tyrosine2

Interactions4

Regulation2

Insulin1

Mediate1

Proteins contain1

Residue2

Clusters1

Zinc finger2

Taxonomic class1

Linker2

Receptor3

Distinct1

Mutations1

Extracellular2

Membrane3

Conformational1

Cellular1

Protein interaction1

Amino acids1

Shown3

Fold1

Conformation1