943 Results for: "AbFrontier"

Supplier: AbFrontier

ζ-chain associated protein kinase, ZAP70, is a 70 kDa member of the Syk family kinase predominantly involved in T cell receptor (TCR) signaling. It is structurally homologous to Syk, a PTK that is involved in proximal BCR signaling. ZAP-70 is a key signaling molecule in T cell activation and also plays a role in apoptosis and cell migration.
SYK family tyrosine kinases contain a C-terminal kinase domain and tandem N-terminal SH2 domains that bind phosphorylated ITAMs (immunoreceptor tyrosine-based activation motif). Linker region that contains multiple tyrosines separates the SH2 domains from the kinase domain. Phosphorylated tyrosines act as docking sites for phospholipase Cγ1 (PLCγ1).
ZAP-70 and Syk are functionally homologous in antigen receptor signaling. Expression of ZAP-70 in Syk− B cells reconstitutes SCR function. Reconstitution requires the presence of functional Src homology 2 (SH2) and catalytic domains of ZAP-70.
Expression of ZAP-70 is an important negative prognostic factor in chronic lymphocytic leukemia (CLL) with more rapid disease progression and shorter survival.

Supplier: AbFrontier

The mitochondrial protein Smac/DIABLO(second mitochondria-derived activator) performs a critical function in apoptosis by eliminating the inhibitory effect of IAPs (inhibitor of apoptosis proteins) on caspases. The newly synthesized Smac protein contains 239 amino acids. Its N-terminal 55 residues encode the mitochondrial-targeting sequence and are proteolytically removed in the mature Smac protein. In the intrinsic cell death pathway, the key event leading to the activation of caspases is the release of several pro-apoptotic proteins such as Smac/DIABLO from the intermembrane space of mitochondria into the cytosol. During apoptosis, Smac is released from mitochondria and re-activates the processed initiator and effector caspases by relieving IAP-mediated inhibition. Furthermore, Smac/DIABLO plays an important regulatory role in the sensitization of cancer cells to both immune-and drug-induced apoptosis.

Supplier: AbFrontier

A growing body of evidence relates selenium to cancer prevention, immune system function, male fertility, cardiovascular disorder, control of the aging and neurodiseases process. Selenoproteins are thought to be responsible for the majority of these biomedical effects of selenium. Approximately 17 selenoproteins have been identified until now. Although the function of many selenoproteins are unknown, some play important roles in anti-oxidant mechanisms. It has been also implicated in the regulation of  signaling pathways through catalysis of thiol/ disulfide exchange.
Selenoprotein M(SelM) is especially expressed in a mammalian brain and is localized to the perinuclear structures (Golgi/ER). The roles of selM have not been clearly identified until present time.

Supplier: AbFrontier

Peroxiredoxin (Prx) is a growing peroxidase family, whose mammalian members have been known to connect with cell proliferation, differentiation, and apoptosis.
Many isoforms (about 50 proteins), collected in accordance to the amino acid sequence homology, particularly amino-terminal region containing active site cysteine residue, and the thiol-specific antioxidant activity, distribute throughout all the kingdoms. Among them, mammalian Prx consists of 6 different members grouped into typical 2-Cys, atypical 2-Cys Prx, and 1-Cys Prx. Except Prx VI belonging to 1-Cys Prx subgroup, the other five 2-Cys Prx isotypes have the thioredoxin-dependent peroxidase (TPx) activity utilizing thioredoxin, thioredoxin reductase, and NADPH as a reducing system. Mammalian Prxs are 20 – 30 kilodalton in molecular size and vary in subcellular localization: Prx I, II, and VI in cytosol, Prx III in mitochondria, Prx IV in ER and secretion, Prx V showing complicated distribution including peroxisome, mitochondria and cytosol.

Supplier: AbFrontier

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, with a prevalence of 1–2% in population aged 65 years or older. PD is a complex, multifactorial disorder that typically manifests after the age of 50 years.
The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. α-synuclein and parkin are thought to be firmly associated with PD.
The exact biological function of the DJ-1 protein is currently unknown. It may play a role in the oxidative stress response, and this function could be important in preventing the onset of PD. Defects in PARK7 are the cause of autosomal recessive early-onset Parkinson disease 7 (PARK7).
The human DJ-1 protein contains 189 amino acid residues. DJ-1 may possess an active site and could also be a protease/hydrolase similar to the PfpI proteases.
The DJ-1 gene has been highly conserved in evolution. The structures of the mouse and human DJ-1 genes are similar, and human and mouse DJ-1 proteins display 90% amino acid identity.

Supplier: AbFrontier

p53 is a transcription factor that regulates the cell cycle and hence functions as a tumor suppressor. p53 has been described as "the guardian of the genome", referring to its role in conserving stability by preventing genome mutation. p53 has many anti-cancer mechanisms: activating DNA repair proteins when DNA has sustained damage, holding the cell cycle at the G1/S regulation point on DNA damage recognition, initiating apoptosis if the DNA damage proves to be irrepairable. Human p53 is 393 amino acids long and has three domains: N-terminal transcription-activation domain (TAD), which activates transcription factors. 2) central DNA-binding core domain (DBD) 3) C-terminal homo-oligomerisation domain (OD); tetramerization greatly increases the activity of p53 in vivo. Mutations that deactivate p53 in cancer usually occur in the DBD and most of these mutations destroy the ability of the protein to bind to its target DNA sequences.

Supplier: AbFrontier

Peroxiredoxin (Prx) is a growing peroxidase family, whose mammalian members have been known to connect with cell proliferation, differentiation, and apoptosis.
Many isoforms (about 50 proteins), collected in accordance to the amino acid sequence homology, particularly amino-terminal region containing active site cysteine residue, and the thiol-specific antioxidant activity, distribute throughout all the kingdoms. Among them, mammalian Prx consists of 6 different members grouped into typical 2-Cys, atypical 2-Cys Prx, and 1-Cys Prx. Except Prx VI belonging to 1-Cys Prx subgroup, the other five 2-Cys Prx isotypes have the thioredoxin-dependent peroxidase (TPx) activity utilizing thioredoxin, thioredoxin reductase, and NADPH as a reducing system. Mammalian Prxs are 20 – 30 kilodalton in molecular size and vary in subcellular localization: Prx I, II, and VI in cytosol, Prx III in mitochondria, Prx IV in ER and secretion, Prx V showing complicated distribution including peroxisome, mitochondria and cytosol (1).

Supplier: AbFrontier

Ezrin, radixin and moesin (ERM) proteins are widely distributed proteins located in the cellular cortex, in microvilli and adherens junctions. They are mediate linkage of actin cytoskeleton to plasma membrane in many cells. ERM proteins contain an N-terminal FERM (4.1/ezrin/radixin/moesin)
domain that binds to phosphatidylinositol-(4,5)phosphate and cellular membrane proteins. The ERM, particularly ezrin, is important for reconstructing cell-surface architecture during T cell activation. Despite the high degree of homology, the three proteins exhibit a distinct receptor-specific pattern of phosphorylation. ERM activity is regulated in part by phosphorylation at a C-terminal threonine(ezrin-Thr567, radixin-Thr564, moesin-Thr558).

Supplier: AbFrontier

The His tag antibody was generated by immunization with highly purified His-tagged proteins produced in E.coli. This antibody reacts with polypeptides which include a 6-His tag.

Supplier: AbFrontier

The Ras superfamily of small GTPases includes the Ras, Rho, Arf, Rab, and Ran families. Ras-regulated signal pathways control such as actin cytoskeletal integrity, proliferation, differentiation, cell adhesion, apoptosis, and cell migration. These GTPases function as molecular switches that control eukaryotic cell function by cycling between two interconvertible forms, a GDP-bound inactive form and a GTP-bound active form. The binding of GTP leads to a conformational change in the downstream effector-binding domain of the G-protein.
The small GTPases are monomeric G-proteins with molecular masses over the range 20–30 kDa. Ras is attached to the cell membrane by prenylation.
Mutations in the Ras family of proto-oncogenes (comprising H-Ras, N-Ras and K-Ras) are very common, being found in 20% to 30% of all human tumours. The frequency of RAS mutations is among the highest for any gene in human cancer. K-ras mutations occur frequently in non-small-cell lung, colorectal, and pancreatic carcinomas; H-ras mutations are common in bladder, kidney, and thyroid carcinomas; N-ras mutations are found in melanoma, hepatocellular carcinoma, and hematologic malignancies.

Supplier: AbFrontier

Receptor protein tyrosine phosphatase rho (RPTPρ/PTPRT) is a transmembrane protein that is highly expressed in the developing and adult central nervous system. It is a member of the RPTP R2B subfamily, which includes PTPκ, PTPμ and PCP-2. The R2B phosphatases are known to interact with members of the cadherin/catenin complex.
These four RPTPs share the same domain structure: an extracelluar domain, a juxtamembrane region, and two phosphatase domains. The extracellular domain of PTPR mediates cell-cell aggregation and that mutational inactivation of this phosphatase could promote tumor migration and metastasis. PTPRT is the most frequently mutated PTP in human cancers. STAT3 is a substrate of PTPRT. Phosphorylation of a tyrosine at 705 is essential for the function of STAT3, and PTPRT specifically dephosphorylated STAT3 at this position.

Supplier: AbFrontier

Caspase-activated DNase (CAD) cleaves chromosomal DNA during apoptosis. Apoptosis which is a cell death process removing toxic and/or useless cells during mammalian development can be induced by a variety of stimuli, including the death factors of the tumor necrosis factor family,  or UV irradiation, anticancer drugs, and survival factor deprivation. The apoptotic process is accompanied by shrinkage and fragmentation of the cells and nuclei and degradation of the chromosomal DNA into nucleosomal units.
CAD, which can be activated by caspases, exists as a complex with its inhibitor, inhibitor of CAD (ICAD). ICAD helps correct folding of CAD and remains complexed with CAD to inhibit the DNase activity of CAD. Caspase, which is activated during the apoptotic process, cleaves ICAD, and the CAD released from ICAD enters the nuclei to cleave the chromosomal DNA. Internal as well as external signals can activate caspases and this is under the control of the balance between pro-and anti-apoptotic proteins of the Bcl-2 family, heat shock proteins, and inhibitors of apoptosis proteins (IAPs). Currently, fourteen members of the caspase family have been identified, of which seven mediate apoptosis.

Supplier: AbFrontier

Diazepam Binding Inhibitor(DBI) is a highly conserved 10 kDa polypeptide which is expressed in various species range from yeast to mammals. As an inverse agonist for benzodiazepine receptors, DBI downregulates inhibitory effects of GABA. It also has potential to induce anxiety. Found in central and peripheral tissues, DBI also participates in metabolism of steroids, which has been known to partially modify GABAA receptor function in the CNS. In peripheral tissues, DBI plays regulatory roles in steroidogenesis. DBI levels have been reported to be decreased in the cerebrospinal fluid obtained from patients with Alzheimer disease.

Supplier: AbFrontier

Ubiquitin(Ub) is a small protein that is composed of 76 amino acids. Ub is found only in eukaryotic organisms and is highly conserved. Ub can exist either in free form or as part of a complex with other proteins. In the latter case, Ub is attached(conjugated) to proteins through a covalent bond between the glycine at the C-terminal end of Ub and the side chains of lysine on the proteins; Ubiquitination.  Ub functions to regulate protein turnover in a cell by closely regulating the degradation of specific proteins. Ubiquitin has been immunohistochemically localized to a number of pathological inclusions, including ; Lewy bodies of Parkinson’s disease,neurofibrillary of Alzheimer’s disease, Pick bodies of Pick’s disease.

Supplier: AbFrontier

The mammalian thioredoxin reductases (TrxRs) are a family of selenocysteine-containing pyridine nucleotide-disulfide oxidoreductases. All the mammalian TrxRs are homologous to glutathione reductase with respect to primary structure including the conserved redox catalytic site (-Cys-Val-Asn-Val-Gly-Cys-) but distinctively with a C-terminal extension containing a catalytically active penultimate selenocysteine (SeCys) residue in the conserved sequence(-Gly-Cys-SeCys-Gly). TrxR is homodimeric protein in which each monomer includes an FAD prosthetic group, a NADPH binding site and a redox catalytic site. Electrons are transferred from NADPH via FAD and the active-site disulfide to C-terminal SeCys-containing redox center, which then reduces the substrate like thioredoxin. The members of TrxR family are 55 - 58 kilodalton in molecular size and composed of three isoforms including cytosolic TrxR1, mitochondrial TrxR2, and TrxR3, known as Trx and GSSG reductase (TGR). TrxR plays a key role in protection of cells against oxidative stress and redox-regulatory mechanism of transcription factors and various biological phenomena (1).

Supplier: AbFrontier

Glutamine Synthetase(GS) catalyzes the conversion of ammonia and glutamate to glutamine. This reaction consumes a molecule of ATP:
Glutamate + NH4+ + ATP
 Glutamine + ADP + Pi
GS is found in astrocytes as an octamer of identical 45kDa subunits. Most well known function of GS is the detoxification of brain ammonia. It also has an important role in controlling metabolic regulations of neurotransmitter glutamate. Because of the multiple functions and importance of GS in cellular metabolism, both catalytic activities and synthesis are highly regulated. The activity of GS is controlled by adenylylation. Its activity is decreased in the cerebral cortex of brains affected by Alzheimer’s disease, particularly in the vicinity of senile plaques. It is also decreased under conditions of glucose deprivation. On the other hands, the level of expression of GS is increased during ischemia in vivo or hypoxia in culture.

Supplier: AbFrontier

Peroxiredoxin (Prx) is a growing peroxidase family, whose mammalian members have been known to connect with cell proliferation, differentiation, and apoptosis. Many isoforms (about 50 proteins), collected in accordance to the amino acid sequence homology, particularly amino-terminal region containing active site cysteine residue, and the thiol-specific antioxidant activity, distribute throughout all the kingdoms. Among them, mammalian Prx consists of 6 different members grouped into typical 2-Cys, atypical 2-Cys Prx, and 1-Cys Prx. Except Prx VI belonging to 1-Cys Prx subgroup, the other five 2-Cys Prx isotypes have the thioredoxin-dependent peroxidase (TPx) activity utilizing thioredoxin, thioredoxin reductase, and NADPH as a reducing system. Mammalian Prxs are 20 – 30 kilodalton in molecular size and vary in subcellular localization: Prx I, II, and VI in cytosol, Prx III in mitochondria, Prx IV in ER and secretion, Prx V showing complicated distribution including peroxisome, mitochondria and cytosol.

Supplier: AbFrontier

Check point kinase 1 (Chk1) is a serine / threonine protein kinase and a key mediator in the DNA damage-induced checkpoint network. Chk1 is an evolutionarily conserved protein kinase that functions to ensure genomic integrity upon genotoxic stress. When the G2 or S checkpoint is abrogated
by the inhibition of Chk1, p53-deficient cancer cells undergo mitotic catastrophe and eventually apoptosis, whereas normal cells are still arrested in the G1 phase. Thus, Chk1 inhibitors can preferentially
potentiate the efficacy of DNA damaging agents in cancer cells, and Chk1 is an attractive therapeutic target for cancer treatment, especially since approximately 50% of all human cancers are p53-deficient.

Supplier: AbFrontier

Plasminogen, a 92kDa glycoprotein, is produced by the liver and is present in plasma and extracellular fluids. Plasminogen is the inactive precursor of plasmin, a potent serine protease involved in the dissolution of fibrin blood clots. Plasminogen can be converted into the active plasmin by plasminogen activators urokinase (uPA), tissue plasminogen activator (tPA), factor XII-dependent components. The plasmin system has been implicated in a variety of physiological and pathological processes such as fibrinolysis, tissue remodeling, cell migration, inflammation, and tumor invasion and metastasis. Hereditary defects of plasminogen is a predisposing risk factor for thromboembolic disease.

Supplier: AbFrontier

ubiquitously expressed proteins which catalyze the reduction of hydrogen peroxides and organic hydroperoxides by glutathione. There are several isoforms which differ in their primary structure and localization. The classical cytosolic/mitochondrial GPx1 (cGPx) is a selenium-dependent enzyme, first of the GPx family to be discovered. GPx2, also known as gastrointestinal GPx (GI-GPx), is an intracellular enzyme expressed only at the epithelium of the gastrointestinal tract (1). Extracellular plasma GPx (pGPx or GPx3) is mainly expressed by the kidney from where it is released into the blood circulation (2). Phospholipid hydroperoxide GPx4 (PH-GPx) expressed in most tissues, can reduce many hydroperoxides including hydroperoxides integrated in membranes, hydroperoxy lipids in low density lipoprotein or thymine (3). All mammalian GPx family members, except for the recently described Cys containing GPx3 and epididymis-specific secretory GPx (eGPx or GPx5) isoforms, possess selenocysteine at the active site (4-5).

Supplier: AbFrontier

Enolase (2-phosphogly-cerate hydrolyase or phosphopyruvate hydrates) is a glycolytic enzyme that catalyzes the dehydration and conversion of 2-phosphoglycerate to phosphoenolpyruvate. It comprises three distinct subunits, alpha, beta and gamma. Non Neuronal Enolase(ENO1) is an isoform of mammalian enolase and is composed of 2 alpha subunits. The gene for ENO1 also encodes a shorter monomeric structural lens protein, tau-crystallin.
Multifunctional enzyme that, as well as its role in glycolysis, plays a part in various processes such as growth control, hypoxia tolerance and allergic responses. May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons. Stimulates immunoglobulin production.
Used as a diagnostic marker for many tumors and, in the heterodimeric form, alpha/gamma, as a marker for hypoxic brain injury after cardiac arrest. Also marker for endometriosis. Antibodies against alpha-enolase are present in sera from patients with cancer-associated retinopathy syndrome (CAR), a progressive blinding disease which occurs in the presence of systemic tumor growth, primarily small-cell carcinoma of the lung and other malignancies. Is identified as an autoantigen in Hashimoto encephalopathy (HE) a rare autoimmune disease associated with Hashimoto thyroiditis (HT). HT is a disorder in which destructive processes overcome the potential capacity of thyroid replacement leading to hypothyroidism

Supplier: AbFrontier

p38 MAPK cascade regulates a variety of cellular responses to stress, inflammation and other signals. p38 MAPK is relatively inactive in the non-phosphorylated form and becomes rapidly activated by dual phosphorylation of a Thr-Gly-Tyr motifs. There are four isoforms of p38 MAPK, , ,  and , which differ in their tissue expression and affinity for upstream activators and downstream effectors.
When cells are exposed to tumor necrosis factor-, interleukin-1, heat shock, or other activating stimuli, activation of MAPK kinase-3 and –6 occurs by phosphorylation. Activated MAPK kinase-3/6 phosphorylate each residue of Thr180 and Tyr182 in p38 MAPK. Phospho-p38 MAPK activates ATF-2, CHOP-1, MEF-2 and other transcription factors through phosphorylation.

Supplier: AbFrontier

IκBα is the major IκB protein member of IκB family that function to inhibit the NF-κB transcription factor. IκBs have an N-terminal regulatory domain, followed by six or more ankyrin repeats and a PEST domain near their C terminus. IκBα inhibits NF-κB by masking the nuclear localization signals (NLS) of NF-κB proteins and keeping them in an inactive state in the cytoplasm. In addition, IκBα blocks the ability of NF-κB transcription factors to bind to DNA, which is required for NF-κB's proper functioning.
Upon stimulation by the proinflammatory cytokine tumor necrosis factor (TNF), signaling pathways lead to activation of the subunit of the IκB kinase (IKK) complex, which then phosphorylates IκB proteins on two N-terminal serine residues. The IKK is an unusual kinase in that it contains two related kinases, IKKα and IKKβ, and a regulatory subunit, NEMO (NF-κB essential modifier). The primary role of NF-κB is to maintain normal cellular functions that range from cell-to-cell communication to cell motility, cell cycle progression, and cell lineage development.

Supplier: AbFrontier

Mitogen-activated protein kinases (MAPKs) are activated by various extracellular signals, such as growth factors, stresses, and cytokines, and play crucial roles in the determination of cell fate through proliferation, differentiation, survival, and apoptosis.
Mnk1(MAP kinase-interacting serine/threonine-protein kinase 1) and Mnk2 are protein kinases that are directly phosphorylated and activated by extracellular signal-regulated kinase (ERK) or p38 mitogen-activated protein (MAP) kinases which phosphorylate at least two threonine residues (Thr197 and Thr202 of the mouse Mnk1) located in the activation loop. Mnks are implicated in the regulation of protein synthesis through their phosphorylation of eukaryotic translation initiation factor 4E (eIF4E), also known as cap-binding protein.
The initiation step of translation is rate-limiting and represents a major target for translational control. The formation of the cap-binding complex eIF4F, which is a multiprotein factor responsible for the recruitment of the 40S ribosomal subunit to the mRNA 5′ end, is a key regulatory step. Mnk1 is physically associated with eIF4F and directly phosphorylate eIF4E, a component of the eIF4F complex. eIF4E specifically binds the 5′ m7GpppN cap structure found in all eukaryotic mRNAs and plays a critical role in cap-dependent translation initiation as a central component of the eIF4F complex, which also contains eIF4A and eIF4G.

Supplier: AbFrontier

Bcl-2 (B-cell lymphoma 2) family govern mitochondrial outer membrane permeabilization (MOMP) and can be either pro-apoptotic (Bax, BAD, Bak, Bid and Bok) or anti-apoptotic (Bcl-2, Bcl-xL, and Bcl-w). Mitochondrial membrane permeabilization and subsequent release of apoptotic factors are key mechanisms during this process.
The members of the Bcl-2 family share one or more of the four characteristic domains of homology entitled the Bcl-2 homology (BH) domains (named BH1, BH2, BH3 and BH4).
Bid consists of only one Bcl-2 homology domain, BH3. Bid cleavage to tBid (truncated Bid) activates apoptotic pathway at the mitochondrial level. Cleavage of cytosolic Bid and subsequent mitochondrial translocation have been detected in neuronal cell death related to acute or chronic neurodegeneration. Pharmacological inhibition of Bid can be a promising therapeutic strategy in neurological diseases where programmed cell death is prominent.
After Bid activation and mitochondrial translocation, the most prominent downstream mechanisms of Bid-dependent neuronal apoptosis involve disruption of mitochondrial membrane integrity and intracellular calcium homoeostasis and the release of pro-apoptotic mitochondrial factors such as cytochrome c.

Supplier: AbFrontier

The Smad family of proteins are functioning in the transmission of extracellular signals in the TGF-β signaling pathway. Binding of a TGF-β superfamily ligands to extracellular receptors triggers phosphorylation of Smad2 at a Serine-Serine-Methionine-Serine (SSMS) motif at its C-terminus. Phosphorylated Smad2 is then able to form a complex with Smad4. These complexes accumulate in the cell nucleus, where they are directly participating in the regulation of gene expression.
In mammals, eight Smad proteins have been identified to date. The Smad family of proteins can be divided into three functional groups: the receptor-activated Smads (R-Smads), common mediator Smads (Co-Smads), and the inhibitory Smads (I-Smads). The R-Smads are directly phosphorylated by the activated type I receptors on their C-terminal Ser-Ser-X-Ser (SSXS) motif and include Smad1, Smad2, Smad3, Smad5, and Smad8. Smad2 and Smad3 are phosphorylated in response to TGF-β and activin, whereas Smad1, Smad5, and Smad8 are phosphorylated in response to BMP (Bone Morphogenetic Protein). This C-terminal phosphorylation allows R-Smad binding to Co-Smad, Smad4, and translocation to the nucleus where they regulate TGF-β target genes. Smad6 and Smad7 belong to the I-Smad which bind to the type I receptor or Smad4 and block their interaction with R-Smads.
The Smads share sequence similarities, most notably in the N-terminal and carboxy-terminal regions, referred to as the MH1 (Mad Homology 1) and MH2 domains respectively. Smad2 and Smad3 have 66% amino acid sequence identity between their MH1 domains and 96% amino acid sequence identity between their MH2 domains.

Supplier: AbFrontier

The complement system is a part of the larger immune system and three biochemical pathways are present: the classical complement pathway, the alternative pathway, and the mannose-binding lectin pathway.
Human complement factor C6 is one of five components (C5b, C6, C7, C8, and C9) that interact to form the cytolytic membrane attack complex (MAC) which is the cytolytic end product of the complement cascade. MAC is typically formed on the surface of intruding pathogenic bacterial as a result of the activation of the complement system, and it is one of the ultimate weapons of the immune system.
The sixth component of complement, C6, is a 913 amino acid single polypeptide chain serum glycoprotein. Homology study suggests that C6 could contain two domains, an amino-terminal region that is related to complement C8 and C9, and a carboxyl-terminal region that has partial homology to the complement regulatory proteins factor H and factor I.
Genetic deficiencies of terminal complement components lead to markedly increased susceptibility to only one particular Gram-negative genus, the Neisseria. The susceptibility is attributable to the major role played by complement-mediated killing in host defense against the pathogen.

Supplier: AbFrontier

Btk (Bruton's tyrosine kinase) is a member of the Tec family of protein tyrosine kinases (PTKs) and plays a modulatory role in many cellular processes, such as proliferation, development, differentiation, survival, and apoptosis. The Tec kinases are the second largest family of non-receptor tyrosine kinases and include Tec, Btk, Bmx, Itk, and TXK/Rlk. Mutations of Btk gene cause a primary immunodeficiency disease in humans, X-linked aγglobulinemia (XLA) which is characterized by a lack of circulating B lymphocytes and an absence of immunoglobulins as a result of defects in B cell maturation and function. Btk is found in all hematopoietic cells, with the exception of T lymphocytes and plasma cells. Btk contains amino-terminal PH (pleckstrin homology) domain which binds phosphatidylinositol (3,4,5)-trisphosphate (PIP3) helping membrane translocation upon PI3 kinase activation. The Tec kinases have similar structure of N-terminal PH domains followed by Tec homology (TH), Src homology 3 (SH3), Src homology 2 (SH2), and kinase domains. Autophosphorylation of Tyr223 in SH3 domain is necessary for full activation of Btk. Various binding proteins have been reported to interact with different domains of Btk.

Supplier: AbFrontier

IκB kinase α (IKKα) is a component of a multiprotein kinase complex that regulates the activity of the transcription factor NF-κB. Activation of the IKK complex via upstream stimuli leads to phosphorylation and degradation of NF-κB bound IκB(Inhibitor of κB). Subsequently, free NF-κB dimers enter the nucleus and regulate the transcription of a variety of target genes involved in cell proliferation and differentiation, apoptosis, and inflammation, etc. The IKK complex consists of 2 highly homologous kinase subunits, IKKα and IKKβ, and a nonenzymatic regulatory component, IKKγ/NEMO. The relative contributions of IKKα and IKKβ to the signalling complex vary according to the requirements of the cell. IKKβ plays a predominant role in immune responses, while IKKα alone appears to be sufficient for at least some developmental systems. Recently, IKK/NF-κB signaling pathway was studied as therapeutic targets in cancer.

Supplier: AbFrontier

The Smad family of proteins are functioning in the transmission of extracellular signals in the TGF-β signaling pathway. Binding of a TGF-β superfamily ligands to extracellular receptors triggers phosphorylation of Smad2 at a Serine-Serine-Methionine-Serine (SSMS) motif at its C-terminus. Phosphorylated Smad2 is then able to form a complex with Smad4. These complexes accumulate in the cell nucleus, where they are directly participating in the regulation of gene expression.
In mammals, eight Smad proteins have been identified to date. The Smad family of proteins can be divided into three functional groups: the receptor-activated Smads (R-Smads), common mediator Smads (Co-Smads), and the inhibitory Smads (I-Smads). The R-Smads are directly phosphorylated by the activated type I receptors on their C-terminal Ser-Ser-X-Ser (SSXS) motif and include Smad1, Smad2, Smad3, Smad5, and Smad8. Smad2 and Smad3 are phosphorylated in response to TGF-β and activin, whereas Smad1, Smad5, and Smad8 are phosphorylated in response to BMP (Bone Morphogenetic Protein). This C-terminal phosphorylation allows R-Smad binding to Co-Smad, Smad4, and translocation to the nucleus where they regulate TGF-β target genes. Smad6 and Smad7 belong to the I-Smad which bind to the type I receptor or Smad4 and block their interaction with R-Smads.