sh3

Adapter protein involved in invadopodia and podosome formation, extracellular matrix degradation and invasiveness of some cancer cells. Binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an organizer protein that allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and ROS localization. In association with ADAM12, mediates the neurotoxic effect of amyloid-beta peptide.

SH3BGRL Protein, Human, Recombinant (GST & His) is expressed in E. coli.

SH3YL1 Protein, Human, Recombinant (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 41.1 kDa and the accession number is Q96HL8.

UBASH3A is a member of the T-cell ubiquitin ligand (TULA) family. This family consists of two members. Both of them can negatively regulate T-cell signaling. UBASH3A can facilitate growth factor withdrawal-induced apoptosis in T cells, which may occur via its interaction with AIF, an apoptosis-inducing factor. Alternative splicing of UBASH3A gene results in multiple transcript variants. It interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases. UBASH3A promotes accumulation of activated target receptors, such as T-cell receptors, EGFR and PDGFRB, on the cell surface. UBASH3A also exhibits negligigle protein tyrosine phosphatase activity at neutral pH. It may act as a dominant-negative regulator of UBASH3B-dependent dephosphorylation. It may also inhibit dynamin-dependent endocytic pathways by functionally sequestering dynamin via its SH3 domain.

NCKIPSD is localized exclusively in the cell nucleus. It plays a role in signal transduction and may function in the maintenance of sarcomeres and the assembly of myofibrils into sarcomeres. NCKIPSD also plays an important role in stress fiber formation. NCKIPSD gene is involved in therapy-related leukemia by a chromosomal translocation t(3;11)(p21;q23) that involves this gene and the myeloid lymphoid leukemia gene. Alternative splicing occurs in this locus and two transcript variants encoding distinct isoforms have been identified. NCKIPSD is an SH3 domain protein. Fas ligand is a cytotoxic effector molecule of T and NK cells which is characterized by an intracellular N-terminal polyproline region that serves as a docking site for SH3 and WW domain proteins. Several previously described Fas ligand-interacting SH3 domain proteins turned out to be crucial for the regulation of storage, expression, and function of the death factor. Recent observations, however, indicate that Fas ligand is also subject to posttranslational modifications including shedding and intramembrane proteolysis.

As an adaptor protein, Growth Factor Receptor-Bound Protein 2 (GRB2) is involved in siganl transduction and consists of a central SH2 domain flanked by two SH3 domains. GRB2 associates with activated Tyr-phosphorylated EGF receptor EGFR and PDGF receptors via its SH2 domain, stimulating GTP binding to Ras, which in turn activates MAPK and other signaling pathway.It also associates to other cellular Tyr-phosphorylated proteins such as SIT1, IRS1, IRS4, SHC and LNK. probably via the concerted action of both its SH2 and SH3 domains.

Cytoplasmic Protein NCK1 (NCK1) is a cytoplasmic protein that contains one SH2 domain and three SH3 domains. NCK1 is a member of the adapter family, which associates with tyrosine-phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. NCK1 maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. NCK1 plays a role in the DNA damage response, but not in the detection of the damage by ATM ATR. It is also involved in transducing signals from receptor tyrosine kinases to downstream signal recipients, such as ELK1-dependent transcriptional activation in response to activated Ras signaling.

LASP1 Protein, Human, Recombinant (His) is expressed in yeast with C-6xHis tag. The predicted molecular weight is 31.2 kDa; 43 kDa, reducing conditions and the accession number is Q14847.

UBASH3B contains a ubiquitin associated domain at the N-terminus, an SH3 domain, and a C-terminal domain with similarities to the catalytic motif of phosphoglycerate mutase. UBASH3B was found to inhibit endocytosis of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor. UBASH3B interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases. It promotes accumulation of activated target receptors, such as T-cell receptors and EGFR, on the cell surface. UBASH3B exhibits tyrosine phosphatase activity toward several substrates including EGFR, FAK, SYK, and ZAP7. Down-regulates proteins that are dually modified by both protein tyrosine phosphorylation and ubiquitination.

Implicated in endocytosis. May recruit other proteins to membranes with high curvature.

G3BP1 Protein, Human, Recombinant (His) is expressed in E. coli.

Adapter protein that plays a role in the assembling of signaling complexes, being a link between ABL kinases and actin cytoskeleton. Can form complex with ABL1 and CBL, thus promoting ubiquitination and degradation of ABL1. May play a role in the regulation of pancreatic cell adhesion, possibly by acting on WASF1 phosphorylation, enhancing phosphorylation by ABL1, as well as dephosphorylation by PTPN12. Isoform 6 increases water and sodium absorption in the intestine and gall-bladder. SORBS2 Protein, Human, Recombinant (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 33.1 kDa and the accession number is O94875.

Neutrophil cytosol factor 1( NCF1) is a 47 kDa cytosolic subunit of neutrophil NADPH oxidase. This oxidase is characterized as a multicomponent enzyme which is activated to produce superoxide anion. NCF2, NCF1, and a membrane bound cytochrome b558 are required for the activation of the latent NADPH oxidase. The human NCF1 gene encodes a 390 amino acids protein without a signal peptide. The NCF1 gene interacts with other subunits of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) and plays an important role in innate immunity, producing reactive oxygen species and reducing the severity and duration of parasitic infection and autoimmune disease. NCF1 also has a role in T cell activation.

ACK1 (also known as ACK, TNK2, or activated Cdc42 kinase) is a structurally unique non-receptor tyrosine kinase that is expressed in diverse cell types. This downstream effector of CDC42 mediates CDC42-dependent cell migration via phosphorylation of BCAR1. The ACK1 protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation signal transduction pathway. ACK1 integrates signals from plethora of ligand-activated receptor tyrosine kinases (RTKs), for example, MERTK, EGFR, HER2 and PDGFR to initiate intracellular signaling cascades. It binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR. ACK1 transduces extracellular signals to cytosolic and nuclear effectors such as the protein kinase AKT PKB and androgen receptor (AR), to promote cell survival and growth. ACK1 participates in tumorigenesis, cell survival, and migration. Gene amplification and overexpression of ACK1 were found in many cancer types such as those of the lung and prostate. Recently, four somatic missense mutations of ACK1, which occur in the N-terminal region, the C-lobe of the kinase domain, and the SH3 domain, were identified in cancer tissue samples.

Tyrosine-Protein Kinase Blk (BLK) contains one protein kinase domain, one SH2 domain and one SH3 domain. BLK is a non-receptor tyrosine kinase, which is involved in B-lymphocyte development, differentiation and signaling. B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors. Signaling through BLK plays an important role in transmitting signals through surface immunoglobulines and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor. Defects in BLK are a cause of maturity-onset diabetes of the young type 11 (MODY11).

Disks large homolog 4(DLG4) is a cell membrane protein and it is a member of the membrane-associated guanylate kinase (MAGUK) family. The protein contains 1 guanylate kinase-like domain，3 PDZ (DHR) domains and 1 SH3 domain. With PSD-93 it is recruited into the same NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. DLG4 is the best studied member of the MAGUK-family of PDZ domain-containing proteins. Like all MAGUK-family proteins, its basic structure includes three PDZ domains, an SH3 domain, and a guanylate kinase-like domain (GK) connected by disordered linker regions. It is almost exclusively located in the post synaptic density of neurons, and is involved in anchoring synaptic proteins. Its direct and indirect binding partners include neuroligin, NMDA receptors, AMPA receptors, and potassium channels.

Proto-oncogene tyrosine-protein kinase Yes, also known as Proto-oncogene c-Yes, p61-Yes and YES1, is a cytoplasm protein that belongs to the protein kinase superfamily, Tyr protein kinase family and SRC subfamily. YES1 c-Yes contains one protein kinase domain, one SH2 domain and one SH3 domain. It is thought that the subcellular distribution of Src-family tyrosine kinases, including c-Yes binding to the cellular membrane, is membranous and or cytoplasmic. YES1 c-Yes protein tyrosine kinase is known to be related to malignant transformation. YES1 c-Yes and c-Src are the two most closely related members of the Src family of nonreceptor tyrosine kinases. Although there is much evidence to support redundancy in signaling between these two kinases. YES1 c-Yes promotes the formation of the tight junction by phosphorylating occludin, while c-Src signaling downregulates occludin formation in a Raf-1 dependent manner. YES1 c-Yes has tyrosine kinase activity. It promotes infectivity of Neisseria gonorrhoeae in epithelial cells by phosphorylating MCP CD46.

Melanoma Inhibitory Activity Protein (MIA) is an autocrine growth regulatory protein secreted from chondrocytes and malignant melanoma cells, which was the first discovered member of a family of secreted cytokines termed the MIA OTOR family. The four known members of this family: MIA, MIA2, OTOR and TANGO each contain a Src homology-3 (SH3)-like domain. MIA acts as a potent tumor cell growth inhibitor for malignant melanoma cells and some other neuroectodermal tumors, including gliomas, in an autocrine fashion and promotes melanoma metastasis by binding competitively to fibronectin and laminin in a manner that results in melanoma cell detachment from the extracellular matrix in vivo. The protein MIA has been shown to represent a very sensitive and specific serum marker for systemic malignant melanoma that might be useful for staging of primary melanomas, detection of progression from localized to metastatic disease during follow-up, and monitoring therapy of advanced melanomas. Elevated levels of MIA may represent a clinically useful marker for diagnosis of melanoma metastasis as well as a potential marker for rheumatoid arthritis.

Protein Kinase C and Casein Kinase Substrate in Neurons Protein 1 (PACSIN1) belongs to the PACSIN family. PACSIN1 contains one FCH domain and one SH3 domain. PACSIN1 is highly expressed in the brain and at lower leves in the heart, pancreas, and liver. PACSIN1 may play a role in vesicle formation and transport. PACSIN1 has been shown to interact with DNM1, PACSIN3, Huntingtin, and PACSIN2. In addition, PACSIN1 is phosphorylated by casein kinase 2 (CK2) and protein kinase C (PKC).

Protein Kinase C and Casein Kinase Substrate in Neurons Protein 2 (PACSIN2) is a member of the PACSIN family. PACSIN2 is localized to the plasma membrane via its coiled-coil domain. PACSIN2 is widely expressed and contains one FCH domain and one SH3 domain. PACSIN2 forms homo- and hetero-aggregates with other PACSINs. PACSIN2 may play a role in vesicle formation and transport. In addition, PACSIN2 is involved in linking the actin cytoskeleton with vesicle formation by regulating tubulin polymerization.

CBL proteins, such as Cbl-c, are phosphorylated upon activation of a variety of receptors that signal via protein tyrosine kinases. Through interactions with proteins containing SRC homology-2 (SH2) and SH3 domains, CBL proteins modulate downstream cell signaling. Cbl-c is a member of the Cbl family of E3 ubiquitin ligases. Expression of Cbl-c gene may be restricted to epithelial cells, and alternatively spliced transcript variants encoding multiple isoforms have been observed for Cbl-c gene.