Src homology 3 domain src homology 1 domain. Medical search. Frequent questions

Several G-protein coupled receptors, such as the beta1-adrenergic receptor (beta1-AR), contain polyproline motifs within their intracellular domains. (duke.edu)
Crk is mainly composed of Src homology 2 (SH2) and Src homology 3 (SH3) domains, which serve as docking sites for signalling proteins, including various receptors, cytoplasmic kinases, and GTPase regulators. (rndsystems.com)
Chronic T-cell exhaustion is marked by the progressive upregulation of coinhibitory receptors, PD-1 being one of the most prominent, but also other coregulated receptors such as LAG-3 ( 4, 5 ). (aacrjournals.org)
BTK interacts with SRC homology 3 domains of FYN, LYN and HCK that are activated upon stimulation of B- and T-cell receptors (1).Defects in the BTK gene cause Agammaglobulinemia, an X-linked immunodeficiency characterized by failure to produce mature B lymphocyte cells and associated with a failure of Ig heavy chain rearrangement. (signalchem.com)
Direct Phosphorylation of SRC Homology 3 Domains by Tyrosine Kinase Receptors Disassembles Ligand-Induced Signaling Networks Molecular Cell , vol. 70 , nº 6. (inrs.ca)

This domain interacts with adaptor molecules and activates a cascade which regulates the inflammatory status in cells [12]. (fortunejournals.com)

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)
Covalent modifications of Src mainly include phosphorylation and oxidization. (xcessbio.com)

PAG3 encodes a multidomain protein containing an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology (PH) domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal Src homology 3 (SH3) domain. (novusbio.com)
Pleckstrin homology domain. (embl.de)
Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. (embl.de)
Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. (embl.de)
Pleckstrin is one of the rare proteins to contains two PH domains. (embl.de)
They usually appear in multidomain proteins, together with catalytic domains, or other protein binding modules, such as Src homology 3 (SH3), phosphotyrosine binding (PTB) or pleckstrin homology (PH) domains. (lu.se)

For example, a region of WASP known as the proline-rich domain can bind to proteins that contain an "SH3" domain. (elifesciences.org)
Signal transducing adaptor proteins that contain SRC HOMOLOGY DOMAINS and play a role in CYTOSKELETON reorganization. (bvsalud.org)

In response to insulin stimulation, this complex bound to tyrosine-phosphorylated IRS-1 (insulin receptor substrate-1) and Shc. (nih.gov)
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)

In terms of initiating the cell cycle when growth factor signals are present, "Src homology domains" are found on Grb2 proteins, allowing them to bind Receptor Tyrosine Kinases (RTKs), and also on SOS proteins allowing them to interact with Grb2. (wikipedia.org)
Here, we show that insulin-induced activation of ERKs was enhanced by stable overexpression of growth factor receptor-bound protein 2 (GRB2) but not by overexpression of GRB2 proteins with point mutations in the Src homology 2 and 3 domains. (nih.gov)
In contrast to the activated epidermal growth factor receptor that binds the GRB2-Sos complex directly, activation of the insulin receptor results in the interaction of GRB2-Sos with IRS-1 and Shc, thus linking the insulin receptor to Ras signaling pathways. (nih.gov)
Endophilin-A2, SH3 domain protein 2B or SH3 Domain-Containing GRB2-Like Protein 1 is encoded by the gene Sh3gl1 and a member of the endophilin family of Src homology 3 domain-containing proteins. (antibodiesinc.com)

MacDonald, SM & Vonakis, BM 2002, ' Association of the Src homology 2 domain-containing inositol 5′ phosphatase (SHIP) to releasability in human basophils ', Molecular Immunology , vol. 38, no. 16-18, pp. 1323-1327. (johnshopkins.edu)
The inositol trisphosphate (IP 3 ) generated by PI-PLC mobilizes Ca 2+ from internal stores ([Ca 2+ ] i ). (jneurosci.org)
The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. (embl.de)

The genome-wide search for disease-causing variations in the SH2 domains revealed eight genes: Bruton tyrosine kinase (BTK), SH2 domain-containing protein 1A (SH2D1A), Ras GTPase activating protein (RasGAP), tyrosine protein kinase Zap-70, SHP-2, the p85α subunit of the PIP3 kinase (PI3-K), signal transducer and activator of transcription 1α/β (STAT1) and STAT5B. (lu.se)

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)
ADAM binding protein Eve-1 is required for ectodomain shedding of epidermal growth factor receptor ligands. (atlasgeneticsoncology.org)
Insulin receptor substrate-1 (IRS-1) and Golgi phosphoprotein 3 (GOLPH3) were overexpressed in ESCC. (spandidos-publications.com)
Smurf2, a member of the HECT domain E3 ligase family, is well known for its role as a negative regulator of TGF-β signaling by targeting Smads and TGF-β receptor. (molcells.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)
OBJECTIVE -Coinhibitory signals mediated via programmed death 1 (PD-1) receptor play a critical role in downregulating immune responses and in maintaining peripheral tolerance. (diabetesjournals.org)
Insulin Receptor Substrate 1 (IRS-1). (embl.de)
AAA peroxins are involved in the export from peroxisomes of Pex5p, the PTS1 (peroxisome-targeting signal type 1) receptor. (tcdb.org)
The GDNF family ligands (GFLs) function through a glycosyl-phosphatidylinositol-(GPI) anchored coreceptor, GDNF family receptor alpha (GFRα), and rearranged during transfection (RET), a well-known receptor tyrosine kinase involved in kidney development, spermatogonial stem cell maintenance, and the development and maintenance of the sympathetic, parasympathetic, and enteric nervous systems [ 1 , 2 ]. (medsci.org)
On the other hand, the C-terminal which is the cytoplasmic domain of TLRs has a homology with interleukin type-1 receptor (IL-1R), known as Toll 1L-1R receptor (TIR) domain [11]. (fortunejournals.com)

The Src-homology 3 (SH3) region is a protein domain consisting of approximately 60 residues. (rcsb.org)
The comparison between the crystal structures of Fyn and spectrin SH3 domains shows that a conserved surface patch, consisting mainly of aromatic residues, is flanked by two hairpin-like loops (residues 94-104 and 114-118 in Fyn). (rcsb.org)
These kinases then phosphorylate specific tyrosine residues (Y446 and Y496) on the intracellular domain of the IL-10R1 chain. (nih.gov)
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)
The Bin1 SH3 domain and the NS5A fragment containing residues 191 to 340 (NS5A(191-340)) were expressed recombinantly as GST-fusions and purified. (biomedcentral.com)
Binding site 1 (B1) comprises NS5A residues 200 to 228 whereas binding site 2 (B2) includes residues 295 to 320. (biomedcentral.com)
Unexpectedly, the α-helical structure was not selected by the SH3 domain, but a disordered one, as the SSP scores in segment B1 dropped down to almost zero, while for B2, they are significantly reduced (although no 13 C chemical shifts could be measured for residues 214-217 and 302-309 due to extensive line broadening). (biomedcentral.com)
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)
The Src homology 2 (SH2) domains are about 100 residues in length with an average of 28% pairwise residue identity (Pfam code PF00017). (lu.se)
SH2 domains mediate intramolecular recognition and intermolecular protein-protein association almost invariably by binding to phosphorylated tyrosine (pY) residues in specific sequence contexts. (lu.se)

Moreover, this interaction is mediated by the C-terminal SH3 domain of SH3p4. (duke.edu)
1. Cheng, G. et al: Binding of Bruton's tyrosine kinase to Fyn, Lyn, or Hck through a Src homology 3 domain-mediated interaction. (signalchem.com)
This interaction appears to be mediated by binding of its SH3 domain to the C-terminal proline-rich domain of PYK2. (novusbio.com)
To study the interaction of Bin1 SH3 domain with NS5A via non-canonical binding sites, we used an NS5A fragment lacking the high-affinity SH3 binding site (PxxP motif). (biomedcentral.com)
Binding of the Bin1 SH3 domain affects the helical segments H1 and H3, which are part of the interaction regions B1 and B2, respectively. (biomedcentral.com)
We identified SLAP2 and ABL2 as potent interaction partners of FLT3 through their SH2 domain. (lu.se)

Both approaches identified SH3p4/p8/p13 (also referred to as endophilin 1/2/3), a SH3 domain-containing protein family, as binding partners for the beta1-AR. (duke.edu)

Such motifs in other proteins are known to mediate protein-protein interactions such as with Src homology (SH)3 domains. (duke.edu)
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)
SH3 domains mediate protein-protein interactions, often via binding to polyproline II helices. (biomedcentral.com)

PD-1 has two cytoplasmic tyrosine motifs: one an immunoreceptor tyrosine-based inhibition motif and the other an immunoreceptor tyrosine-based switch motif (ITSM). (diabetesjournals.org)
The LCS-II connecting D2 and D3 contains two directly neighbored class II PxxP-motifs, which are important for interactions with Src homology 3 (SH3) domains. (biomedcentral.com)

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)
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)

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)
Programmed death 1 (PD-1) is an immunoreceptor of the CD28/CTLA-4 family whose expression is induced in activated T- and B-cells and in macrophages ( 1 , 2 ). (diabetesjournals.org)

The SH3 domain is a 60 amino acids segment shared by diverse structural and signaling proteins [ 6 ]. (oncotarget.com)
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)

The tyrosine kinase Src is activated in a large number of human malignancies and plays significant roles in the development of cancers. (xcessbio.com)
Activation of Src in human cancers employs a variety of mechanisms mainly including covalent modification, allosteric regulation, gene mutation. (xcessbio.com)
Expression of the suppressor of cytokine signaling-1 (SOCS1) is inactivated in hematopoietic and solid cancers by promoter methylation, miRNA-mediated silencing, and mutations. (aacrjournals.org)

Lasp1 (LIM and SH3 domain protein 1) promotes tumor proliferation and invasion in multiple cancer entities including non-small cell lung cancer (NSCLC). (oncotarget.com)
Overexpression of IRS-1 was associated with cell differentiation, whereas GOLPH3 was related to lymph node metastasis, tumor invasion in-depth and TNM stage in ESCC patients. (spandidos-publications.com)
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)
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)
Nck-associated protein 1 (NAP1/NCKAP1) is highly expressed in primary non-small-cell lung cancer (NSCLC) when compared with adjacent normal lung tissues, and its expression levels are strongly associated with the histologic tumor grade, metastasis and poor survival rate of NSCLC patients. (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)

Mol Cancer Ther (2019) 18 (3): 632-641. (aacrjournals.org)

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. (oncotarget.com)
25(1): 193-201, 2022 Dec. (bvsalud.org)

PF cells were found to express regulatory (p85) and catalytic (p110α and p110β) subunits of phosphatidylinositol 3′-kinase (PI3′-kinase). (jneurosci.org)
Two types of phosphatidylinositol 3-kinase from bovine thymus. (wikidata.org)

In biology, a Src homology domain is one of the two small protein binding domains found in the Src oncoprotein. (wikipedia.org)
In contrast, cyclin A binding to E2F-1 impedes PRMT1 methylation and augments PRMT5 methylation, thus ensuring that E2F-1 is locked into its cell-cycle progression mode. (embl.de)
The Tudor domain protein p100-TSN reads the symmetric methylation mark, and binding of p100-TSN downregulates E2F-1 apoptotic activity. (embl.de)
The LIM domain is composed of two sequential zinc-binding modules, which are responsible for binding with DNA [ 5 ]. (oncotarget.com)
The N-terminal domain of TLRs is associated with ligand binding. (fortunejournals.com)

SOS acts as a Guanosine exchange factor (GEF) for Ras, activating Ras to cleave a phosphate group from Raf, causing it to release the 14-3-3 proteins that are keeping it inactive, which through a downstream signalling cascade allows the release of E2F and thus, progression through the Restriction point (R point) in G1 phase of the cell cycle. (wikipedia.org)
IRS-1 and GOLPH3 are downstream targets of miR-126 at the post-transcriptional level in ESCC. (spandidos-publications.com)
In addition, it functions as a substrate and downstream target for PYK2 and SRC, a pathway that may be involved in the regulation of vesicular transport. (novusbio.com)

A protein domain which has the same topology as SH3 is present in the prokaryotic regulatory enzyme BirA. (rcsb.org)

It contains an N-terminal LIM domain and a C-terminal SRC homology region 3 (SH3) domain [ 2 - 4 ]. (oncotarget.com)
[ 4 ] The genetic defect appears to be a region of the gene encoding the KRT14 nonhelical head (E1/V1) domain located between the microsatellite markers D17S798 and D17S957, which are separated by approximately 26.97 cM. (medscape.com)
A nonsense mutation in a corresponding region of KRT5 has been found in Dowling-Degos disease and a missense mutation in the V1 domain of KRT5 has been described in patients with epidermolysis bullosa with mottled pigmentation. (medscape.com)

We describe the residue-specific methylation of E2F-1 by the asymmetric dimethylating protein arginine methyltransferase 1 (PRMT1) and symmetric dimethylating PRMT5 and relate the marks to different functional consequences of E2F-1 activity. (embl.de)
Five friends of methylated chromatin target of protein-arginine-methyltransferase[prmt]-1 (chtop), a complex linking arginine methylation to desumoylation. (embl.de)

The mechanisms that underlie and dictate the different biological outcomes of E2F-1 activity have yet to be elucidated. (embl.de)
Our results define an exquisite level of precision in the reader-writer interplay that governs the biological outcome of E2F-1 activity. (embl.de)
Biological assembly 1 assigned by authors. (rcsb.org)

The Src homology 1 domain was an early name of the protein kinase domain. (wikipedia.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)
Here we report the crystal structure of the SH3 domain of Fyn (a Src family tyrosine kinase) at 1.9 A resolution. (rcsb.org)
These loops are different in tyrosine kinase and spectrin SH3 domains. (rcsb.org)
Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. (embl.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)
In a humanized mouse non-small cell lung carcinoma model, TSR-033 boosted the antitumor efficacy of PD-1 monotherapy, with a concomitant increase in immune activation. (aacrjournals.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)

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)

Primary Antibody diluted 1:1000. (novusbio.com)

To test our hypothesis that histone H4R3 and H3R17 methylation regulates ferritin transcription, H4R3 and H3R17 protein arginine (R) methyltransferases 1 and 4 (PRMT1 and PRMT4) were investigated. (embl.de)

Basophils from these donors released histamne to HrHRF, IL-3 and D 2 O. While there has been a significant amount of work elucidating signal transduction events in human basophils, the reason for this hyperreleasable phenotype remained illusive. (johnshopkins.edu)

Western Blot: PAG3 Antibody [NBP2-24614] - Analysis of ASAP2 in human brain lysate using 1) preimmune sera at 1:5000 and 2) protein A purified this antibody. (novusbio.com)
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)
More than 100 different human SH2 domains have been identified or predicted. (lu.se)
This concern was depicted in 4-tier Human Development Index (HDI) of the United Nation [3]. (fortunejournals.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)
HGF forms a family with HGF-like protein (HLP), a unique protein with a domain structure similar to that of HGF ( 12 ). (spandidos-publications.com)
One of these genes, SOCS-3 (Suppressor of Cytokine Signaling-3) is a member of a newly identified family of genes that inhibit JAK/STAT-dependent signaling. (nih.gov)

Lasp1 (LIM and SH3 domain protein 1), localized on chromosome 17q11-21.3, was first identified in 1995 [ 1 ]. (oncotarget.com)

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)

In yeast, Arp2/3-mediated actin filament assembly drives endocytic membrane invagination and vesicle scission. (elifesciences.org)

Methylation by PRMT1 hinders methylation by PRMT5, which augments E2F-1-dependent apoptosis, whereas PRMT5-dependent methylation favors proliferation by antagonizing methylation by PRMT1. (embl.de)
miR-126 mimics downregulated the expression of IRS-1 and GOLPH3 protein and suppressed the proliferation, migration and invasion of ESCC cells, whereas miR-126 inhibitors led to the opposite results. (spandidos-publications.com)

The ability of E2F-1 to prompt apoptosis in DNA damaged cells coincides with enhanced PRMT1 methylation. (embl.de)

Anatomy22

Organisms11

Diseases1

Chemicals and Drugs121

Analytical, Diagnostic and Therapeutic Techniques and Equipment31

Phenomena and Processes68

Information Science4

Receptors5

Interacts1

Phosphorylation2

Pleckstrin6

Proteins that contain2

Tyrosine-phosphorylated2

Grb24

Inositol3

Subunit1

Receptor10

Residues11

Interaction6

Endophilin1

Mediate3

Motifs2

Interactions2

Macrophages2

Amino2

Cancers3

Tumor6

Characterized genes1

20191

20222

Phosphatidylinositol 3-Kina2

Binding5

Downstream3

Regulatory1

Region3

Protein-arginine-methyltransferase2

Biological3

Kinase5

Activation3

Cysteine-rich1

Primary Antibody1

Transcription1

Signal1

Human4

Family3

Chromosome1

Antibody1

Arp21

Proliferation2

Apoptosis1