20% off purchase of 3 or more products* | Learn More >>

Product listing: EAAT3 (E1E6M) Rabbit mAb, UniProt ID P43005 #14501 to Integrin α5 (D7B7G) Rabbit mAb, UniProt ID P08648 #98204

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunofluorescence (Frozen), Immunoprecipitation, Western Blotting

Background: During neurotransmission, glutamate is released from vesicles of the presynaptic cell, and glutamate receptors (e.g., NMDA Receptor, AMPA Receptor) bind glutamate for activation at the opposing postsynaptic cell. Excitatory amino acid transporters (EAATs) regulate and maintain extracellular glutamate concentrations below excitotoxic levels (1,2). In addition, glutamate transporters may limit the duration of synaptic excitation by an electrogenic process in which the transmitter is cotransported with three sodium ions and one proton, followed by countertransport of a potassium ion (1,2). Five EAATs (EAAT1-5) have been identified. EAAT1 and EAAT2 are expressed mainly in glia, while EAAT3, EAAT4, and EAAT5 are considered to be neuronal transporters (2). EAAT3 is found in the perisynaptic areas and cell bodies of glutamatergic and GABAergic neurons (3). Research studies have implicated abnormal EAAT3 expression in the pathophysiology of Schizophrenia (4,5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunofluorescence (Immunocytochemistry), Immunoprecipitation, Western Blotting

Background: Nucleotide excision repair (NER) is a process by which cells identify and repair DNA lesions resulting from chemical or radiation exposure (1). XPC forms a complex with HR23B (2) that acts as a damage sensor due to its high affinity for geometry distorting DNA lesions. This complex localizes to sites of DNA damage and recruits the remaining members of the preincision complex necessary for initiation of NER (3). XPC is one of eight NER proteins (XPA-G, XPV) where defects result in Xeroderma pigmentosum, a disease characterized by sunlight sensitivity, a predisposition to cancer of exposed tissue, and, in some instances, neurological defects (4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: B cell maturation antigen (BCMA/TNFRSF17/CD269) is a transmembrane glycoprotein and member of the TNFR superfamily (1). BCMA expression is largely restricted to the B-cell lineage. Pro-survival signaling through this receptor plays a pivotal role in humoral immunity by regulating B-cell maturation and plasma cell differentiation upon binding its ligands, BAFF and APRIL (2-6). BCMA is expressed in a number B-cell malignancies and has garnered much attention as a novel therapeutic target for the treatment of multiple myeloma due to its selective and elevated expression on the cell surface of malignant plasma cells (7-10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Western Blotting

Background: MEK1 and MEK2, also called MAPK or Erk kinases, are dual-specificity protein kinases that function in a mitogen activated protein kinase cascade controlling cell growth and differentiation (1-3). Activation of MEK1 and MEK2 occurs through phosphorylation of two serine residues at positions 217 and 221, located in the activation loop of subdomain VIII, by Raf-like molecules. MEK1/2 is activated by a wide variety of growth factors and cytokines and also by membrane depolarization and calcium influx (1-4). Constitutively active forms of MEK1/2 are sufficient for the transformation of NIH/3T3 cells or the differentiation of PC-12 cells (4). MEK activates p44 and p42 MAP kinase by phosphorylating both threonine and tyrosine residues at sites located within the activation loop of kinase subdomain VIII.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: XPB and XPD are ATPase/helicase subunits of the TFIIH complex that are involved in nucleotide excision repair (NER) to remove lesions and photoproducts generated by UV light (1). XPB and XPD are 3’-5’ and 5’-3’ DNA helicases, respectively, that play a role in opening of the DNA damage site to facilitate repair (2,3). XPB and XPD both play an important role in maintaining genomic stability, and researchers have linked mutations of these proteins to Xeroderma Pigmentosum (XP) and Trichothiodystrophy (TTD). XP patients have abnormalities in skin pigmentation and are highly susceptible to skin cancers, while TTD patients exhibit symptoms such as brittle hair, neurological abnormalities, and mild photosensitivity (4). In addition to their role in NER, XPB and XPD are involved in transcription initiation as part of the TFIIH core complex (5). The helicase activity of XPB unwinds DNA around the transcription start site to facilitate RNA polymerase II promoter clearance and initiation of transcription (6). XPD plays a structural role linking core TFIIH components with the cdk-activating kinase (CAK) complex that phosphorylates the C-terminus of the largest subunit of RNA polymerase II, leading to transcription initiation (7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Immunoprecipitation, Western Blotting

Background: SHank-Associated RH domain-interacting ProteIN (Sharpin), also known as SIPL1, is a highly conserved gene among many mammalian species and is ubiquitously expressed in various types of cells and tissues. Sharpin harbors multiple functional motifs including an amino terminal coiled-coil (CC) domain, which has been shown to mediate the interaction between sharpin and the scaffold protein shank (1). The other two domains, ubiquitin-like domain (UBL) and NPL4 zinc finger domain (NZF), facilitate ubiquitin-mediated protein recognition and degradation (2). Recent studies have shown that both UBL and NZF domains are essential for sharpin to exert its function in part through ubiquitin-mediated mechanisms (3-5). Although sharpin was initially identified as a scaffold protein within the postsynaptic density of neurons (1), recent studies have identified sharpin as a novel modulator of immune and inflammatory diseases. An emerging mechanistic model suggests that sharpin functions as an important adaptor component of the linear ubiquitin chain assembly complex (LUBAC) that modulates activation of the canonical NF-κB signaling pathway (3,4,6,7), thereby regulating cell survival and apoptosis, cytokine production, and development of lymphoid tissues. Indeed, mice with spontaneous mutations in the Sharpin gene develop chronic proliferative dermatitis that is characterized by eosinophilic inflammation of the skin and dysregulated development of lymphoid tissues (8).

$122
20 µl
$303
100 µl
APPLICATIONS
REACTIVITY
Mouse

Application Methods: Western Blotting

Background: Platelet derived growth factor (PDGF) family proteins exist as several disulphide-bonded, dimeric isoforms (PDGF AA, PDGF AB, PDGF BB, PDGF CC, and PDGF DD) that bind in a specific pattern to two closely related receptor tyrosine kinases, PDGF receptor α (PDGFRα) and PDGF receptor β (PDGFRβ). PDGFRα and PDGFRβ share 75% to 85% sequence homology between their two intracellular kinase domains, while the kinase insert and carboxy-terminal tail regions display a lower level (27% to 28%) of homology (1). PDGFRα homodimers bind all PDGF isoforms except those containing PDGF D. PDGFRβ homodimers bind PDGF BB and DD isoforms, as well as the PDGF AB heterodimer. The heteromeric PDGF receptor α/β binds PDGF B, C, and D homodimers, as well as the PDGF AB heterodimer (2). PDGFRα and PDGFRβ can each form heterodimers with EGFR, which is also activated by PDGF (3). Various cells differ in the total number of receptors present and in the receptor subunit composition, which may account for responsive differences among cell types to PDGF binding (4). Ligand binding induces receptor dimerization and autophosphorylation, followed by binding and activation of cytoplasmic SH2 domain-containing signal transduction molecules, such as GRB2, Src, GAP, PI3 kinase, PLCγ, and NCK. A number of different signaling pathways are initiated by activated PDGF receptors and lead to control of cell growth, actin reorganization, migration, and differentiation (5). Tyr751 in the kinase-insert region of PDGFRβ is the docking site for PI3 kinase (6). Phosphorylated pentapeptides derived from Tyr751 of PDGFRβ (pTyr751-Val-Pro-Met-Leu) inhibit the association of the carboxy-terminal SH2 domain of the p85 subunit of PI3 kinase with PDGFRβ (7). Tyr740 is also required for PDGFRβ-mediated PI3 kinase activation (8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse

Application Methods: Western Blotting

Background: The kindlin family of focal adhesion proteins is involved in multiple biological processes, including integrin signaling, adhesion, migration, angiogenesis, differentiation, and mitotic spindle formation (1,2). Kindlin family members 1, 2, and 3 (FERM1, FERM2, and URP2) are differentially expressed in tissues. Kindlin-1 is primarily expressed in epithelial cells, kindlin-2 is ubiquitously expressed, and kindlin-3 expression is restricted to the hematopoietic system (3).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Western Blotting

Background: La-related protein 1 (LARP1) is a ubiquitously expressed RNA binding protein that promotes both global and specific mRNA translation in cells (1). LARP1 belongs to the La-related protein family and contains two RNA binding domains, a La motif (LAM), and a neighboring RNA recognition motif-like (RRM-L) domain (1). Research studies indicate that LARP1 acts downstream of mTORC1 to facilitate cell proliferation and growth by promoting global mRNA translation and translation of mRNAs containing a 5'Terminal Oligo-Pyrimidine (5'TOP) motif, which code for translational machinery components (2,3). At the molecular level, LARP1 associates with 5'TOP mRNAs and multiple translation machinery components to positively regulate translation (2,4). Additional studies show that LARP1 expression is upregulated in hepatocellular carcinoma (HCC) patients and that high LARP1 expression in HCC negatively correlates with survival rate (5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Immunoprecipitation, Western Blotting

Background: TRIBBLES proteins belong to a small family of serine-threonine kinase-like proteins characterized by the presence of a variant protein kinase motif (lacking a canonical ATP binding site), a MEK-1 binding site, and a C-terminal COP1 site that binds ubiquitin ligase. The tribbles gene was first identified and characterized in Drosophila genetic screens for genes that regulate cell division, gastrulation and oogenesis (1-3). Research studies in Drosophila suggested that Tribbles functions to coordinate cell division by regulating turnover of the cell cycle protein String/cdc25. In contrast to the Drosophila genome, which contains a single tribbles gene, the genomes of mice and humans encode three known TRIBBLES proteins (TRIB1-3), which exhibit both distinct and overlapping patterns of expression and functions (4). For example, TRIB1 and TRIB2, but not TRIB3, were reported to promote degradation of the basic region-leucine zipper transcription factor C/EBPα, a function that appears to be conserved from flies to humans (5,6). TRIB2 is overexpressed in a subset of human AML patient samples, down-regulated in leukemic cells undergoing proliferation arrest (7), and positively regulated by the NOTCH signaling pathway in T cells (8), while retroviral-mediated overexpression of Trib2 in mice was shown to induce transplantable leukemia (7). These finding collectively suggest that TRIB2 functions as an oncogene in the mammalian hematopoietic system (9).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Western Blotting

Background: The DYRK family includes several dual-specificity tyrosine-phosphorylated and regulated kinases capable of phosphorylating proteins at both Tyr and Ser/Thr residues (1). The DYRK family was identified based on homology to the yeast Yak1 (2) and the Drosophila minibrain (mnb) kinases (3). Seven mammalian isoforms have been discovered, including DYRK1A, DYRK1B, DYRK1C, DYRK2, DYRK3, DYRK4, and DYRK4B. Differences in substrate specificity, expression, and subcellular localization are seen across the DYRK family (4,5). All DYRK proteins have a Tyr-X-Tyr motif in the catalytic domain activation loop; phosphorylation of the second Tyr residue (e.g. Tyr312 of DYRK1A) is necessary for kinase activity. DYRKs typically autophosphorylate the Tyr residue within their activation loop, but phosphorylate substrates at Ser and Thr residues (1,6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: The sequences encoding antigen receptors are split into multiple germline segments which are then combined by a process called V(D)J recombination during immune cells development. A variable (V) segment is combined with a joining (J) segment, and in some cases a D (Diversity) segment, to create the antigen-binding portion of the receptor. The recombined V(D)J segment is then spliced into exons that encode the constant region to produce mature mRNA (1,2). This essential process required for the development of functional immune T and B cells creates a vast diversity in these receptors (3,4). Initiation of this process follows binding of RAG1 (recombination activating gene 1) and RAG2 to the conserved recombination signal sequences (RSS) and the introduction of a double-strand break between the RSS and the coding sequence (5,6). RAG1 and RAG2 genes are located immediately adjacent to each other in the genome and lack introns in their coding regions in many species. RAG1 and RAG2 are coexpressed only in the B and T cell lineages and both are required for cleavage activity (7). RAG1 and RAG2 can also function as transposases, contributing to chromosomal translocations and lymphoid malignancy (8,9). Mutations in the RAG genes are associated with a spectrum of combined immune deficiencies in humans (10,11).

$262
50-100 transfections
300 µl
SignalSilence® c-Myc siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit c-Myc expression by RNA interference, a method whereby gene expression can be selectively silenced through the delivery of double stranded RNA molecules into the cell. All SignalSilence® siRNA products from CST are rigorously tested in-house and have been shown to reduce target protein expression by western analysis.
REACTIVITY
Human

Background: Members of the Myc/Max/Mad network function as transcriptional regulators with roles in various aspects of cell behavior including proliferation, differentiation and apoptosis (1). These proteins share a common basic-helix-loop-helix leucine zipper (bHLH-ZIP) motif required for dimerization and DNA-binding. Max was originally discovered based on its ability to associate with c-Myc and found to be required for the ability of Myc to bind DNA and activate transcription (2). Subsequently, Max has been viewed as a central component of the transcriptional network, forming homodimers as well as heterodimers with other members of the Myc and Mad families (1). The association between Max and either Myc or Mad can have opposing effects on transcriptional regulation and cell behavior (1). The Mad family consists of four related proteins; Mad1, Mad2 (Mxi1), Mad3 and Mad4, and the more distantly related members of the bHLH-ZIP family, Mnt and Mga. Like Myc, the Mad proteins are tightly regulated with short half-lives. In general, Mad family members interfere with Myc-mediated processes such as proliferation, transformation and prevention of apoptosis by inhibiting transcription (3,4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Insulin-like growth factor-II mRNA-binding proteins (IMPs) belong to a family of zipcode-binding proteins (1,2). Three members of this family, IMP1, IMP2, and IMP3, have been identified (1,2). They contain two RNA recognition motifs, four K homology domains, and were found to function in mRNA localization, turnover, and translation control (1,2). Research studies have implicated these proteins in a variety of physiological and pathological processes, such as growth and development (3), testicular neoplasia (4), and melanocytic neoplasia (5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Protein ubiquitination is an important posttranslational modification that regulates protein function and fate (1). Ubiquitin (Ub) can be conjugated to target proteins in either monomeric or polymeric forms. There are several different lysine residues within Ub that can be used as conjugation sites for poly-Ub chain formation. Different poly-Ub linkages mediate different functions of the target protein ranging from alterations in protein function to degradation (2). UBE2N/Ubc13 is a ubiquitin-E2-conjugating enzyme that catalyzes K63-linked poly-Ub chain formation (1,2). UBE2N forms a heterodimer with MMS2 or Uev1A to exert its E2 ligase function. The UBE2N/MMS2 and UBE2N/Uev1A heterodimers catalyze different modes of target protein ubiquitination to mediate various signaling pathways (3-5) including: DNA damage and recombination, p53 and check point control, the cell cycle (6-10), immunoreceptor signaling (11,12), and endocytosis (13). Most recently, UBE2N was shown to play an important role in inflammatory signaling by promoting K63-linked ubiquitination and activation of IKK downstream of the IL-1β receptor (14). Furthermore, interaction of UBE2N with the Triad1 E3 protein-ubiquitin ligase was shown to play an important role in myelopoiesis (15).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunofluorescence (Frozen), Immunohistochemistry (Paraffin)

Background: T-box, brain, 1 (TBR1) is a transcription factor important in vertebrate embryo development. As a member of T-Box family of transcription factors, TBR1 is expressed in postmitotic glutamatergic projection neurons (1). During cortical neurogenesis, sequential expression of transcription factors Pax6, TBR2, and TBR1 regulates discrete steps in projection neuron differentiation (2). TBR1 is enriched in layer 6 of the developing cortex. In the absence of TBR1, TBR1 mutants exhibit profound defects in frontal cortex and layer 6 differentiation, suggesting that TBR1 regulates regional and laminar identity of postmitotic cortical neurons (3). Therefore, TBR1 expression can be used as a marker for postmitotic glutamatergic neurons and cortical laminar specificity.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunofluorescence (Immunocytochemistry), Immunoprecipitation, Western Blotting

Background: The COP9 Signalosome (CSN) is a ubiquitously expressed multiprotein complex that is involved in a vast array of cellular and developmental processes, which is thought to be attributed to its control over the ubiquitin-proteasome pathway. Typically, the CSN is composed of eight highly conserved subunits (CSN1-CSN8), each of which is homologous to one of the eight subunits that form the lid of the 26S proteasome particle, suggesting that these complexes have a common evolutionary ancestor (1). CSN was first identified in Arabidopsis thaliana mutants with a light-grown seedling phenotype when grown in the dark (2-4). The subsequent cloning of the constitutive morphogenesis 9 (cop9) mutant from Arabidopsis thaliana was soon followed by the biochemical purification of the COP9-containing multiprotein complex (4). It is now widely accepted that the CSN directly interacts with cullin-RING ligase (CRL) families of ubiquitin E3 complexes, and that CSN is required for their proper function (5). In addition, CSN may also regulate protein homeostasis through its association with protein kinases and deubiquitinating enzymes. Collectively, these activities position the CSN as a pivotal regulator of the DNA-damage response, cell-cycle control, and gene expression (1).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Bone morphogenetic proteins (BMPs) were first identified as molecules that can induce ectopic bone and cartilage formation (1,2). BMPs belong to the TGF-β superfamily, playing many diverse functions during development (3). BMPs are synthesized as precursor proteins and then processed by cleavage to release the C-terminal mature BMP. BMPs initiate signaling by binding to a receptor complex containing type I and type II serine/threonine receptor kinases that then phosphorylate Smad (mainly Smad1, 5, and 8), resulting in the translocation of Smad into the nucleus. BMP was also reported to activate MAPK pathways in some systems (3,4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Chromatin IP, Immunoprecipitation, Western Blotting

Background: The modulation of chromatin structure is an essential component in the regulation of transcriptional activation and repression. Modifications can be made by at least two evolutionarily conserved strategies, through the disruption of histone-DNA contacts by ATP-dependent chromatin remodelers, or by histone tail modifications including methylation and acetylation. One of the four classes of ATP-dependent histone remodelers is the SWI/SNF complex, the central catalytic subunit of which is Brg1 or the highly related protein hBRM (1). This SWI/SNF complex contains varying subunits but its association with either Brg1 or hBRM remains constant (1). SWI/SNF complexes have been shown to regulate gene activation, cell growth, the cell cycle and differentiation (1). Brg1/hBRM have been shown to regulate transcription through enhancing transcriptional activation of glucocorticoid receptors (2). Although usually associated with transcriptional activation, Brg1/hBRM have also been found in complexes associated with transcriptional repression including HDACs, Rb and Tif1β (3-5). Brg1/hBRM plays a vital role in the regulation of gene transcription during early mammalian embryogenesis. In addition, Brg1/hBRM also plays a role as a tumor suppressor and Brg1 is mutated in several tumor cell lines (6-8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Topoisomerase II Binding Protein 1 (TopBP1) contains eight BRCT domains, which facilitate interaction with various proteins, phosphopeptides, and DNA. Through these interactions, TopBP1 functions in the regulation of DNA replication, DNA repair, checkpoint control, and transcription (1). TopBP1 contacts the checkpoint kinase ATR and its binding partner ATRIP, and induces ATR and Chk1 activation in collaboration with claspin (2,3). Activation of ATR is dependent on recruitment of TopBP1 through the MRN (MRE11-RAD50-NBS1) complex, and the 911 (RAD9-RAD1-HUS1) complex is required for full activation (4). TopBP1 stabilizes Bloom syndrome helicase (BLM) during S phase of the cell cycle to suppress sister chromatin exchange and maintain genome stability (5).TopBP1 also regulates initiation of DNA replication along with the DNA replication factor treslin (6,7). TopBP1 has been shown to prevent replication associated DNA damage during neurogenesis (8), and to interact with mutant p53, mediating mutant p53 gain-of-function activity such as growth promotion and resistance to chemotherapeutic drugs (9). Phosphorylation of TopBP1 at Ser1159 by Akt regulates TopBP1 oligomerization and function in E2F1-dependent transcriptional regulation (10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Western Blotting

Background: Phosphorylation of the eukaryotic initiation factor 2 (eIF2) α subunit is a well-documented mechanism to downregulate protein synthesis under a variety of stress conditions. eIF2 binds GTP and Met-tRNAi and transfers Met-tRNA to the 40S subunit to form the 43S preinitiation complex (1,2). eIF2 promotes a new round of translation initiation by exchanging GDP for GTP, a reaction catalyzed by eIF2B (1,2). Kinases that are activated by viral infection (PKR), endoplasmic reticulum stress (PERK/PEK), amino acid deprivation (GCN2), or heme deficiency (HRI) can phosphorylate the α subunit of eIF2 (3,4). This phosphorylation stabilizes the eIF2-GDP-eIF2B complex and inhibits the turnover of eIF2B. Induction of PKR by IFN-γ and TNF-α induces potent phosphorylation of eIF2α at Ser51 (5,6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Divalent metal-ion transporter 1 (DMT1, SLC11A2, NRAMP2) is a transmembrane metal ion transport protein that plays critical roles in non-heme iron absorption in the intestine and iron acquisition by erythroid precursor cells (1,2). Following the cellular uptake of iron, DMT1 transfers ferric iron from the endosomes to the cytoplasm (3,4). The DMT1 protein can transport up to eight different metals, including iron, manganese, cobalt, and cadmium (5). Four mammalian DMT1 isoforms are expressed in various tissues and are differentially regulated at both the transcriptional and post-translational level (6,7). Mutations in the corresponding SLC11A2 gene can result in hypochromic microcytic anemia and iron overload. Aberrant iron transport in these individuals results in erythroid hyperplasia, high serum iron, and impaired liver function (8-10). Research studies show elevated DMT1 levels and iron accumulation in the substantia nigra of Parkinson's disease patients and the corresponding animal model (11,12).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Histone cell cycle regulation defective homolog A (HIRA), also known as TUP1-like enhancer of split protein 1 (TUPLE1), is the mammalian homolog of the yeast HIR1 and HIR2 transcriptional repressor proteins (1). HIRA interacts with UBN1, CABIN, and ASF1A in the cell nucleus to form the evolutionarily conserved HUCA histone chaperone complex that deposits the variant histone H3.3 into chromatin in a DNA-replication independent manner (2). HIRA is required for deposition of histone H3.3 at the transcription start sites of genes, where incorporation of histone H3.3 facilitates nucleosome destabilization and contributes to transcriptional activation (3-5). Histone H3.3 is also linked to gene silencing and is incorporated into regions of the genome thought to be transcriptionally inactive (5-7). While some incorporation of H3.3 into heterochromatin is facilitated by a different histone chaperone complex that contains ATRX and DAXX (ie. telomeric incorporation of H3.3), HIRA is required for incorporation of histone H3.3 and formation of senescence-associated heterochromatin foci (SAHF) during cellular senescence (5-8). HIRA is ubiquitously expressed during mouse embryonic development (9). In the adult mouse, HIRA is expressed at high levels in the kidney, skeletal muscle, and pancreas, but it is expressed at lower levels in the heart, lung, placenta, brain, and liver (9). A missing copy of the HIRA gene on human chromosome region 22q11.2 is a common characteristic of DiGeorge syndrome patients and insufficient production of the HIRA protein may disrupt normal embryonic development (9).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: NCAM (neural cell adhesion molecule, CD56) is an adhesion glycoprotein with five extracellular immunoglobulin-like domains followed by two fibronectin type III repeats. Structural diversity is introduced by alternative splicing resulting in different cytoplasmic domains (1). NCAM mediates neuronal attachment, neurite extension and cell-cell interactions through homo and heterophilic interactions. PSA (polysialic acid) post-translationally modifies NCAM and increases the metastatic potential of small cell lung carcinoma, Wilms+ tumor, neuroblastoma and rhabdomyosarcoma (2). CD56 and CD16 are commonly used to identify NK cells although some cells with the T cell markers CD3 and CD4 also express CD56 (3).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Aquaporin 2 (AQP2) is a water transport protein that forms water channels in kidney tubules and plays a predominant role in controlling organism water homeostasis (1). Members of the aquaporin family are multiple pass transmembrane proteins that form homotetramers to facilitate the flow of water across the plasma membrane. At least thirteen aquaporins have been indentified to date (AQP0 through AQP12) and together this family of small, hydrophobic proteins plays a role in an array of biological processes that include urine formation, cell motility, fertilization, cell junction formation and regulation of overall water homeostasis (2). AQP2 tetramers form water channels that facilitate water transport and excretion in the kidney (3). This transport protein is localized to the plasma membrane is response to endocrine signaling. Posterior pituitary hormones arginine vasopressin (AVP) and ADH regulate osmotic water cell permeability by triggering phosphorylation and subsequent exocytosis of AQP2 (1,4). Mutations in the corresponding AQP2 gene cause a rare form of diabetes known as nephrogenic diabetes insipidus. This autosomal dominant disorder is characterized by abnormal water reabsorption by kidney tubules due, in part, to either nonfunctional or mislocalized AQP2 protein (5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: The 26S proteasome is a highly abundant proteolytic complex involved in the degradation of ubiquitinated substrate proteins. It consists largely of two sub-complexes, the 20S catalytic core particle (CP) and the 19S/PA700 regulatory particle (RP) that can cap either end of the CP. The CP consists of two stacked heteroheptameric β-rings (β1-7) that contain three catalytic β-subunits and are flanked on either side by two heteroheptameric α-rings (α1-7). The RP includes a base and a lid, each having multiple subunits. The base, in part, is composed of a heterohexameric ring of ATPase subunits belonging to the AAA (ATPases Associated with diverse cellular Activities) family. The ATPase subunits function to unfold the substrate and open the gate formed by the α-subunits, thus exposing the unfolded substrate to the catalytic β-subunits. The lid consists of ubiquitin receptors and DUBs that function in recruitment of ubiquitinated substrates and modification of ubiquitin chain topology (1,2). Other modulators of proteasome activity, such as PA28/11S REG, can also bind to the end of the 20S CP and activate it (1,2).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Immunoprecipitation, Western Blotting

Background: Protein ubiquitination and deubiquitination are reversible processes catalyzed by ubiquitinating enzymes and deubiquitinating enzymes respectively (1,2). Deubiquitinating enzymes (DUBS) are categorized into five subfamilies based on catalytic domain structure: USP, UCH, OTU, MJD, and JAMM. The deubiquitinase cellular zinc-finger anti-NF-κB (Cezanne-1, OTUD7B) is an OTU family deubiquitinase that contains amino-terminal catalytic and ubiquitin-associated (UBA) domains, and a carboxy-terminal A20-like zinc finger (A20-ZnF) that is involved in ubiquitin binding (3,4). Research studies demonstrate that Cezanne-1 negatively regulates canonical NF-κB signaling induced by TNF receptor signaling by removing K63-linked ubiquitin chains from the RIP1 adaptor protein (5,6). Cezanne-1 negatively regulates non-canonical NF-κB signaling through the deubiquitination and stabilization of the TRAF3 signal transduction protein (7). Additional research suggests that Cezanne-1 is a breast cancer oncogene as the corresponding OTUD7B gene is amplified in a subset of breast cancers and enhances EGFR signaling through a mechanism involving receptor stabilization (8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunohistochemistry (Paraffin), Western Blotting

Background: T cell Ig- and mucin-domain-containing molecules (TIMs) are a family of transmembrane proteins expressed by various immune cells. TIM-1 (HAVCR1 (hepatitis A virus cellular receptor 1), KIM-1 (kidney injury molecule-1) was originally identified as a receptor for hepatitis A virus (1). TIM-1 also acts as a costimulatory receptor on T cells and following activation, associates with the TCR complex to upregulate signaling and cytokine production (2-5). Another TIM family member, TIM-4, is expressed by antigen presenting cells and is a ligand for TIM-1 (6). TIM-1 expressed by Th1 and Th17 cells was also recently shown to interact with P-selectin to mediate T cell trafficking during inflammation and autoimmune disease (7). NKT cells also express TIM-1, and engagement of TIM-1 on NKT cells leads to increased production of IL-4, but decreased production of IFN-gamma (8). TIM-1 is also a receptor for phosphatidylserine exposed by cells undergoing apoptosis. Detection of phosphatidylserine by TIM-1 expressed on NKT cells results in activation, proliferation, and cytokine production (9). Expression of TIM-1 on regulatory B cells is required for optimal production of IL-10. Mice lacking the TIM-1 mucin domain have decreased production of IL-10 by regulatory B cells, hyperactive T cells, increased levels of inflammatory cytokines, and enhanced severity of autoimmune disease (10,11). In addition, TIM-1 polymorphisms are associated with susceptibility to atopic diseases including asthma (12,13). Finally, expression of TIM-1 is increased in renal tubular epithelial cells following kidney injury (14).

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

Background: Tight junctions, or zona occludens, form a continuous barrier to fluids across the epithelium and endothelium. They function in regulation of paracellular permeability and in the maintenance of cell polarity, blocking the movement of transmembrane proteins between the apical and the basolateral cell surfaces (reviewed in 1). Zona occludens proteins ZO-1, -2, and -3 (also known as TJP1, 2, and 3) are peripheral membrane adaptor proteins that link junctional transmembrane proteins such as occludin and claudin to the actin cytoskeleton (reviewed in 2). ZO-1 and -2 are required for tight junction formation and function (3,4). In subconfluent proliferating cells, ZO-1 and ZO-2 have been shown to colocalize to the nucleus and play a role in transcriptional regulation, possibly through facilitating nuclear import/export of transcriptional regulators (5-7). The ZO-2 gene is transcribed from two promoters, generating the ZO-2A and ZO-2C isoforms. ZO-2C lacks a 23 amino acid amino-terminal sequence found in other ZO-2 isoforms. While both isoforms appear to be widely expressed, abnormal regulation of the ZO-2 gene may be correlated with development of ductal cancer (8).

$260
100 µl
APPLICATIONS
REACTIVITY
Hamster, Human, Monkey, Mouse, Rat

Application Methods: Western Blotting

Background: Integrins are α/β heterodimeric cell surface receptors that play a pivotal role in cell adhesion and migration, as well as in growth and survival (1,2). The integrin family contains at least 18 α and 8 β subunits that form 24 known integrins with distinct tissue distribution and overlapping ligand specificities (3). Integrins not only transmit signals to cells in response to the extracellular environment (outside-in signaling), but also sense intracellular cues to alter their interaction with the extracellular environment (inside-out signaling) (1,2).Integrin α5/β1 is involved in multiple biological processes including embryonic development, angiogenesis and tumor metastasis (4,5). By interaction with its fibronectin ligand, α5/β1 transduces signals that regulate cell adhesion, migration, matrix assembly and cytoskeletal organization (6).