Sequence functional src homology 3 domain. Medical search. Frequent questions

STAT3 binds to these sites via its SH2 (Src homology 2) domain, and is, in turn, tyrosine-phosphorylated by the receptor-associated JAKs. (nih.gov)
The Tir protein of EPEC binds NCK1/NCK2 SH2 domains through a high affinity pYDEV motif ( Frese,2006 ). (eu.org)
The PX domain of Vam7p selectively binds PtdIns-3-P, while the PX domain of the CPK PI-3 kinase selectively binds PtdIns-4,5-P(2). (embl.de)
Physiologically, the N-terminal domain of p126 binds the Src-homology 3 (SH3) domain of c-Abl, leading to activation of the MAPK/ERK2 kinase. (molcells.org)
PIP3 binds to the pleckstrin homology (PH) domains of PKB, recruits it to the membrane where it is phosphorylated and converted to its activated form. (justia.com)
The chromo-domain binds histone H3 tails methylated on lysine 9. (cipsm.de)
We have generated a high affinity and selective humanized monoclonal IgG4 antibody, TSR-033, which binds human LAG-3 and serves as a functional antagonist, enhancing in vitro T-cell activation both in mixed lymphocyte reactions and staphylococcal enterotoxin B-driven stimulation assays. (aacrjournals.org)

Therefore, the causal genes and pathways are still not well known and additional genomic functional analyses are required to elucidate the biological mechanism between genetic variants and the risk of cervical cancer [ 12 , 13 ]. (jcancer.org)
Future research will focus on comparative viral genomic sequencing with the goals of identifying potential sources of FCoV infection and identifying features that may have contributed to the development of FIP in this species. (bvsalud.org)
Now, the genomic sequencing of organisms promises to be a major contributor to this field. (rupress.org)

Based on primary sequence comparisons, β subunits are predicted to be modular structures composed of five domains (A-E) that are related to the large family of membrane-associated guanylate kinase proteins. (jneurosci.org)
Because induction of collagen synthesis is associated with phosphatidylinositol 3-kinase (PI3K) activation, we designed a FAP-targeted PI3K inhibitor that selectively targets FAP-expressing human IPF lung fibroblasts and potently inhibited collagen synthesis. (bvsalud.org)
The Src Homology 2 (SH2) domain is a major protein interaction module that is central to tyrosine kinase signaling. (eu.org)
To address the possibility that activation of phosphatidylinositol-3-kinase (PI3K) and the mammalian target of rapamycin (mTOR/FRAP), represents one of these pathways, we have examined the effect of simultaneous inhibition of the Ras-MAPK and PI3K-mTOR pathways on transformation of CEF by v-Src. (embl.de)
The enzyme is activated by the second messenger PIP3 produced by PI′-3-kinase. (justia.com)
Since PKB activation is PI′-3-kinase dependent, the persistent activation of certain protein tyrosine kinases, such as IGF−1 receptor, EGF receptor, PDGF receptor, pp60c-Src, and the like, leads to the persistent activation of PKB which is indeed encountered in many tumors. (justia.com)
The primary Ly-49D signaling for IFN-γ production is predominately mediated through Src kinase pathways involving membrane proximal events, whereas MIP1α and MIP1β gene induction is more complex and may involve multiple biochemical pathways. (aai.org)

These Ly-49 inhibitory receptors, as well as inhibitory KIRs, contain cytoplasmic immune receptor tyrosine-based inhibitory motifs (ITIMs) that are phosphorylated upon stimulation, leading to the recruitment of Src homology 2 domain-containing protein tyrosine phosphatase (SHP-1) and attenuation of intracellular signals ( 1 , 4 , 5 ). (aai.org)
In contrast, the predicted amino acid sequences for the activating receptors, Ly-49D and Ly-49H, do not contain any ITIMs in their cytoplasmic domains, confirming that these are not inhibitory receptors ( 6 , 7 , 8 , 9 ). (aai.org)

So far, common variants in the SHANK1 gene were reported to be associated with reduced auditory working memory in SCZ 36 and a rare de novo loss-of-function mutation affecting SHANK1 was recently found in a large-scale exome-sequencing study. (nature.com)
Thus, the ability of IL-10 to inhibit gene expression in monocytes is associated with its ability to rapidly induce synthesis of SOCS-3. (nih.gov)
We have identified new isoform of DLG2 gene, which contains 3'-end exons of the known DLG2 gene along with the hypothetical gene FLJ37266. (biomedcentral.com)
We discovered a very large uncharacterized gene containing WD40 and SH3 domains ( AHI1 ), and extended the annotation of four previously characterized genes ( MYB , ALDH8A1 , HBS1L and PDE7B ). (biomedcentral.com)
The N-terminal A domain differs among the four subtypes of Ca 2+ channel β subunits (β 1 -β 4 ) primarily as the result of two duplications of an ancestral gene containing multiple alternatively spliced exons. (jneurosci.org)
You can find over 440 noted mutations within the calpain 3 gene up to now, included in this 212 (50%) are missense mutations, a lot of which alter its catalytic activity (22). (exposed-skin-care.net)
The protein encoded by this gene is an unusual orphan receptor that contains a putative ligand-binding domain but lacks a conventional DNA-binding domain. (cancerindex.org)
This gene is highly expressed in fetal brain and encodes a protein of relative molecular mass 91K, named oligophrenin-1, which contains a domain typical of a Rho-GTPase-activating protein (rhoGAP). (embl-heidelberg.de)
Comparisons of the domain distributions in eukaryotes and prokaryotes enabled distinctions to be made between the domains originating prior to the last common ancestor of all known life forms and those apparently originating as consequences of horizontal gene transfer events. (embl.de)
A variety of approaches, including biochemical purification, gene isolation by homology, and genetic screens, have been successfully used for the identification of putative protein kinases and phosphatases. (rupress.org)
Lymphocyte activation gene-3 (LAG-3) is a coinhibitory receptor associated with impaired T-cell function and is frequently coexpressed with programmed cell death protein-1 (PD-1) in the context of human cancers. (aacrjournals.org)
The postsynaptic protein Shank3 (SH3 and multiple ankyrin repeat domains) is of particular interest, as the loss of a single allele of the SHANK3 gene is sufficient to cause profound cognitive symptoms in children. (jneurosci.org)

East-Asian-type- cagA has a higher binding affinity for the Src homology-2 domain-containing phosphatase 2 (SHP2), resulting in a higher risk of peptic ulcer and/or gastric cancer than Western-type- cagA [ 4 - 7 ]. (biomedcentral.com)

Src Homology 2 (SH2) domains are small modular domains found within a great number of proteins involved in different signalling pathways. (eu.org)
Transformation by v-Src: Ras-MAPK and PI3K-mTOR mediate parallel pathways. (embl.de)
This suggests that other Ras-independent pathways contribute to transformation by v-Src. (embl.de)
Moreover, genetic and simple obesity share similar structural and functional features of dysbiosis, such as higher production of toxins with known potential to induce metabolic deteriorations (e.g. trimethylamine-N-oxide and indoxyl sulphate), higher abundance of genomes containing genes coding enzymes involved in the production of these toxic co-metabolites and higher abundance of pathways for biosynthesis of bacterial antigens (such as endotoxin) [13-15]. (deepdyve.com)

SH2 domains are phosphotyrosine recognition domains, often mediating transient interactions with target proteins. (eu.org)
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)

All NSP proteins contain an NH 2 -terminal SH2 (Src homology domain 2) domain, a central proline/serine-rich domain, and a COOH-terminal domain with modest homology to Ras subfamily GDP-exchange factors (GEFs). (molvis.org)
Members of a subfamily of these enzymes share a specific domain that was first identified in the yeast Sac1 protein [1]. (embl.de)

Owing to the generation of vast amounts of sequencing data by using cost-effective, high-throughput sequencing technologies with improved computational approaches, many putative proteins have been discovered after assembly and structural annotation. (genominfo.org)
Putative proteins are typically annotated using a functional annotation system that uses extant databases, but the expansive size of these databases often causes a bottleneck for rapid functional annotation. (genominfo.org)
We developed SFannotation, a simple and fast functional annotation system that rapidly annotates putative proteins against four extant databases, Swiss-Prot, TIGRFAMs, Pfam, and the non-redundant sequence database, by using a best-hit approach with BLASTP and HMMSEARCH. (genominfo.org)
Since large numbers of putative proteins were discovered from a vast amount of sequencing data generated using high-throughput sequencing technologies, including those of the next and third generation, many automated functional annotation systems have contributed greatly to the annotation of them with minimal manual effort [ 2 ]. (genominfo.org)
However, their runtime performance of functional annotation against large extant databases often causes a bottleneck, and especially, standalone tools, such as AutoFACT [ 3 ] and BLANNOTOR [ 4 ], demand high-performance hardware resources for fast annotation from users. (genominfo.org)
As best-hit approaches, especially bidirectional best-hit [ 12 ], have been widely utilized in searching reliable homologous protein sequences, such as orthologs, as well as functional annotation systems [ 13 , 14 , 15 , 16 ], SFannotation can reliably annotate putative proteins. (genominfo.org)

Calpain 3 provides 54 and 51% series homology towards the 80 kDa subunits of - and m-calpains, respectively, and stocks similar properties with one of these ubiquitously portrayed calpains such as for example Ca2+- reliant activation and maximal activity at natural pH (1). (exposed-skin-care.net)
The proposed VWA domains in integrin beta subunits have recently been substantiated using sequence-based methods. (embl.de)

pp60c-src has less affinity for the detergent-insoluble cellular matrix than do pp60v-src and other viral protein-tyrosine kinases. (wikidata.org)

To address if SHANK2 variants are associated with SCZ, we sequenced SHANK2 in 481 patients and 659 unaffected individuals. (nature.com)
Four out of fifteen non-synonymous variants identified in the SCZ cohort (S610Y, R958S, P1119T and A1731S) were selected for functional analysis. (nature.com)
All four variants revealed functional impairment to various degrees, as a consequence of alterations in spine volume and clustering at synapses and an overall loss of presynaptic contacts. (nature.com)
pp60c-src variants containing lesions that affect phosphorylation at tyrosines 416 and 527. (wikidata.org)
Although genome-wide association studies (GWAS) have successfully identified multiple genetic variants associated with cervical cancer, the functional role of those variants is not well understood. (jcancer.org)

An increase in the level of active, GTP-bound Ras is not necessary for transformation of chicken embryo fibroblasts (CEF) by v-Src. (embl.de)

Functional IL-10 receptor (IL-10R) complexes are tetramers consisting of two IL-10R1 polypeptide chains and two IL-10R2 chains. (nih.gov)
Binding of IL-10 to the extracellular domain of IL-10R1 activates phosphorylation of the receptor-associated Janus tyrosine kinases, JAK1 and Tyk2. (nih.gov)
The FH1 domain is also a binding site for diverse SH3-domain containing proteins like Src-like non-receptor tyrosine kinases, WISH (WASP-interacting SH3 protein) and IRSp53 (insulin receptor substrate) in mammals, and Hof1p in yeast [ 6 ]. (biomedcentral.com)
Insulin receptor substrate-1 (IRS-1) and Golgi phosphoprotein 3 (GOLPH3) were overexpressed in ESCC. (spandidos-publications.com)
The binding of a growth factor brings the multiple monomeric receptor chains into close proximity resulting into the trans-phosphorylation of their cytoplamic domains, which consequently activates downstream signaling cascades. (openrheumatologyjournal.com)

30 Mutations of all three SHANK family members, SHANK1-3, have already been associated to neurodevelopmental disorders like autism spectrum disorders (ASDs) or intellectual disability (ID). (nature.com)
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)
A number of human diseases arise from mutations in VWA domains. (embl.de)
Mutations in K + channel sequences can lead to a variety of clinical disorders exemplifying their physiological importance [ 3 ]. (ersjournals.com)

The domain is composed of seven alpha helices. (embl-heidelberg.de)

C-terminal PTS1 [(SAC)-(KRH)-(LM)] and N-terminal PTS2 [(RK)-(LIV)-X 5 -(HQ)-(LA)] targeting sequences are recognized by Pex5p and Pex7p, respectively, which may shuttle with the substrate protein to the peroxisomal lumen. (tcdb.org)
In addition, ST5 enhanced activation of Src and Syk, a Src substrate, in response to RANKL. (molcells.org)

A Disintegrin and Metalloproteases (ADAM), originally named metalloproteinases disintegrin cystein-rich (MDC), are membrane-anchored cell surface proteins containing both disintegrin and metalloproteinase domains. (frontiersin.org)
Protein modules such as FVYE domains and PH domains that bind specifically to PtdIns 3-phosphate (PtdIns-3-P) and polyphosphoinositides, respectively, can direct such membrane targeting. (embl.de)
In addition, the double mutant (Y42A/L48Q) of the PX domain of Vam7p, reported to cause vacuolar trafficking defects in yeast, has a dramatically decreased level of binding to PtdIns-3-P. These data reveal that the membrane targeting function of the Vam7p PX domain is based on its ability to associate with PtdIns-3-P, analogous to the function of FYVE domains. (embl.de)
In yeast, Arp2/3-mediated actin filament assembly drives endocytic membrane invagination and vesicle scission. (elifesciences.org)

We also identified several genes that do not appear to be protein coding, and generated 17 kb of novel transcript sequence data from re-sequencing 97 EST clones. (biomedcentral.com)

Based on the amino acid sequence homology and biological activity in macrophages, Shimamoto et al ( 15 ) identified that HLP was identical to MSP ( 15 ). (spandidos-publications.com)

Over 120 SH2 domains are predicted in the human genome ( Liu,2011 ). (eu.org)

Formins are multidomain proteins defined by a conserved FH2 (formin homology 2) domain with actin nucleation activity preceded by a proline-rich FH1 (formin homology 1) domain. (biomedcentral.com)
Our results demonstrate that SH3 (Src homology 3) domain-PRM (proline-rich motif) interactions involving multivalent linker proteins play central roles in concentrating NPFs at endocytic sites. (elifesciences.org)
For example, a region of WASP known as the proline-rich domain can bind to proteins that contain an "SH3" domain. (elifesciences.org)

It encodes the inactive pre-pro-HGF, a single chain of 728 amino acids (83 kDa), which includes a signal sequence ( 1 - 31 ), a heavy α chain (69 kDa), and a light β chain (34 kDa). (spandidos-publications.com)

Then, using BLASTP and HMMSEARCH, SFannotation searches homologous proteins and domains in each refined database using a default threshold (≤10 -5 E-value) and selects the highest-scoring homolog to annotate putative proteins as the best-hit approach, such as single best hit and bidirectional best hit [ 12 , 16 ]. (genominfo.org)

EPIYT sequences were more prevalent than EPIYA sequences (P = 0.01) in the EPIYA-B motif of all types of cagA. (biomedcentral.com)

In vitro, the FH2 domain competes with barbed-end capping proteins and is necessary and sufficient to nucleate actin polymerization, but the FH1 domain, which interacts with profilin-actin, funnels actin to the nucleation vicinity and confers full activity to the molecule [ 1 ]. (biomedcentral.com)
Nck-associated protein 1 (NAP1/NCKAP1), a protein that associates with the Src homology 3 (SH3) domain of NCK protein both in vitro and in intact cells, was found to localize along the lamellipodia and to mediate contact-dependent cell migration [ 4 ]. (biomedcentral.com)

Val and Pro confer high-affinity binding at pY+3 - Ala and Ile are tolerated but confer weaker binding. (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)

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)

The inhibitory Ly-49 receptors, Ly-49A, C, G, and I, inhibit NK cell function upon binding of class I ligands on target cells ( 1 , 2 , 3 ). (aai.org)

Actin-related protein 2/3 (Arp2/3) complex activation by nucleation promoting factors (NPFs) such as WASP, plays an important role in many actin-mediated cellular processes. (elifesciences.org)

Once phosphorylated, these tyrosine residues (and their flanking peptide sequences) serve as temporary docking sites for the latent transcription factor, STAT3 (signal transducer and activator of transcription-3). (nih.gov)
Emerging evidence provided insight into the role of signal transducer and activator of transcription 3 (STAT3) in energy metabolism. (biomedcentral.com)

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

Moreover, the ability of IL-10 to induce de novo synthesis of SOCS-3 in monocytes correlates with its ability to inhibit expression of many genes in these cells, including endotoxin-inducible cytokines such as tumor necrosis factor-alpha (TNF-alpha) and IL-1. (nih.gov)

To establish the relationship between formins of Dictyostelium and other organisms we constructed a phylogenetic tree based on the alignment of FH2 domains. (biomedcentral.com)

Taken together, these findings provide the first evidence of ST5 involvement in positive regulation of osteoclastogenesis via Src/Syk/calcium signaling. (molcells.org)
Our insights demonstrate the importance and functional regulation of the HSP90-NAP1 protein complex in cancer metastatic signaling, which spur new avenues to target this interaction as a novel approach to block NSCLC metastasis. (biomedcentral.com)

The power of the thiol proteinases to cleave a multitude of substrates in response to calcium mineral activation allows their involvement in a variety of cell processes offering cell motility, sign transduction, apoptosis, cell differentiation and legislation of the cytoskeleton (3). (exposed-skin-care.net)

These kinases then phosphorylate specific tyrosine residues (Y446 and Y496) on the intracellular domain of the IL-10R1 chain. (nih.gov)
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)
Inspection of known binders reveals that weak residues are tolerated at pY+3 when pY+1 is strong and vice-versa, but are not tolerated at both positions. (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)

VWA domains in extracellular eukaryotic proteins mediate adhesion via metal ion-dependent adhesion sites (MIDAS). (embl.de)

This domain is also known as the breakpoint cluster region-homology (BH) domain. (embl-heidelberg.de)
The sequence of the second repeat region was found to differ considerably between East-Asian-type- cagA and Western-type- cagA . (biomedcentral.com)

With the exception of ForI and ForC all other formins conform to the domain structure GBD/FH3-FH1-FH2-DAD, where DAD is the Diaphanous autoinhibition domain and GBD/FH3 is the Rho GTPase-binding domain/formin homology 3 domain that we propose to represent a single domain. (biomedcentral.com)
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 other two positions important for binding are pY+3 and pY+1. (eu.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)
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)
In contrast, the PX domain of Vps5p displays no binding to any PtdInsPs that were tested. (embl.de)
Agrin-like glycoproteins and proteins with sugar-binding domains are also predominant. (biomedcentral.com)

The protein contains both SH2 and SH3 domains which are often found in intracellular kinases. (nih.gov)
Intracellular VWA domains and homologues in prokaryotes have recently been identified. (embl.de)
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)

Analogous studies in a murine syngeneic tumor model using surrogate antibodies demonstrated significant synergy between LAG-3 and PD-1 blockade-combination treatment led to a marked improvement in therapeutic efficacy, increased T-cell proliferation, IFNγ production, and elicited durable immunologic memory upon tumor rechallenge. (aacrjournals.org)
Tumor persistence leads to sustained exposure of T cells to neoantigens-this results in repeated cycles of activation which culminate in a state of severe T-cell dysfunction or exhaustion, characterized by distinct epigenetic and transcriptional profiles ( 1-3 ). (aacrjournals.org)

AND-34/BCAR3 (Breast Cancer Anti-Estrogen Resistance 3) associates with the focal adhesion adaptor protein, p130CAS/BCAR1. (molvis.org)

Here we demonstrate that PSRP1 is not a bona fide ribosomal protein, but rather a functional homologue of the Escherichia coli cold-shock protein pY. (cipsm.de)

Non-phosphorylated peptides do not bind to the SH2 domains. (eu.org)
Phox homology domains specifically bind phosphatidylinositol phosphates. (embl.de)
Here we show that two representative Phox homology (PX) domains selectively bind to specific phosphatidylinositol phosphates. (embl.de)

Also, PKB is overexpressed in 15% of ovarian cancers, 12% of pancreatic cancers and 3% of breast cancers, and was shown to produce a survival signal that protects cells from apoptosis thus contributing to resistance to chemotherapy. (justia.com)

For physiological or pathological understanding of bone disease caused by abnormal behavior of osteoclasts (OCs), functional studies of molecules that regulate the generation and action of OCs are required. (molcells.org)

Activation of the oncogenic potential of the avian cellular src protein by specific structural alteration of the carboxy terminus. (wikidata.org)
A major difference was found between the distributions of enzyme families that are typically found in all three divisions of cellular life and non-enzymatic domain families that are usually eukaryote-specific. (embl.de)

The A1731S variant was identified in four unrelated SCZ patients (0.83%) but not in any of the sequenced controls and public databases ( P =4.6 × 10 −5 ). (nature.com)

The interaction between SH2 domains and their substrates is however dependent also on cooperative contacts of other surface regions. (eu.org)

Taken together, the pharmacologic activity of TSR-033 demonstrates that it is a potent anti-LAG-3 therapeutic antibody and supports its clinical investigation in cancer patients. (aacrjournals.org)
3) T cell deficiencies result usually in combined immunodeficiencies (CIDs), where both T cells and antibody production are defective. (lu.se)

CAPN3 provides some exclusive domains including its NH2-terminal domains I which has 20C30 additional proteins not within - and m-calpains and two exclusive insertion sequences' of 62 and 77 proteins on the COOH-terminal parts of domains II (known as Is normally1) and domains III (known as IS2). (exposed-skin-care.net)

Comparison of the mechanisms that govern the production of calcium carbonate (CaCO 3 ) biominerals in hexacorallians (scleractinians) and octocorallians is thus expected to shed light on the conservation of the protein toolkit used by these organisms for making their biocalcification. (biomedcentral.com)

Anatomy22

Organisms11

Diseases1

Chemicals and Drugs121

Analytical, Diagnostic and Therapeutic Techniques and Equipment31

Phenomena and Processes68

Information Science4

Binds7

Genomic3

Kinase7

Cytoplasmic2

Gene12

Shp21

Pathways4

Phosphotyrosine2

Subfamily2

Annotation6

Subunits2

Protein-tyrosin1

Variants5

Chicken embryo fibroblasts1

Receptor5

Mutations4

Alpha helices1

Substrate2

Membrane4

Transcript1

Biological1

Human genome1

Proline-rich3

Amino1

Putative1

Motif1

Vitro2

Affinity2

Motifs2

Ligands1

Arp21

STAT32

Proteins contain1

Induce1

Alignment1

Regulation2

Cytoskeleton1

Residues5

Mediate1

Region2

Binding7

Intracellular3

Tumor2

Adaptor1

Demonstrate1

Bind3

Cancers1

Regulate1

Cellular2

0.831

Substrates1

Antibody2

Insertion1

Calcium1