204129 Results for: "Amberlite\u00AE+HPR4200+(Cl)&pageNo=50"

Supplier: Bioss

ADAM11 was first described as MDC (Metalloproteinase-like disintergin-like cysteine-rich protein) from analysis of human brain libraries, in search of brain-specific proteins. Two splice variants with different carboxyterminal ends were described. The message was found only in the brain in this publication. Another group identified ADAM11 in the human brain, where ADAM11 was thought to be involved in cell migration and spatial patterning. ADAM11 was mapped to 17q21.3, a region of interest for breast cancer, and mutations in ADAM11 are associated with some breast cancers. Retinoic acid caused a doubling in ADAM11 message levels over 24 hours in NT2/D1 cells, a human embryonic carcinoma cell line. ADAM11 null mutant mice have deficits in spatial learning and motor coordination, although they did have normal cell migration and differentiation during development. ADAM11 is a member of the ADAMs family (A Disintegrin And Metalloproteinase), but does not contain the canonical HExxHxxxxH zinc-binding metalloproteinase catalytic site. The domain structure of the full-length ADAM11 includes a signal sequence, propeptide domain, metalloproteinase-like domain, disintegrin-like domain, cys-rich domain, EGF-like domain, a spacer region, then the transmembrane domain and a short cytoplasmic domain.

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ErbB3 is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. ErbB3 is a membrane-bound protein which has a neuregulin binding domain but not an active kinase domain. It can therefore bind this ligand but cannot convey a signal into the cell via protein phosphorylation. However it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers including prostate, bladder and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. Isoform 2 lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported but they have not been thoroughly characterized. Defects in ERBB3 are the cause of lethal congenital contracture syndrome type 2 (LCCS2); also called Israeli Bedouin multiple contracture syndrome type A. LCCS2 is an autosomal recessive neurogenic form of a neonatally lethal arthrogryposis that is associated with atrophy of the anterior horn of the spinal cord.

Supplier: Bioss

DNA methylation, or the addition of methyl groups to cytosine bases in the dinucleotide CpG, is imperative to proper development and regulates gene expression. The methylation pattern involves the enzymatic processes of methylation and demethylation. The demethylation enzyme was recently found to be a mammalian protein, which exhibits demethylase activity associated to a methyl-CpG-binding domain (MBD). The enzyme is able to revert methylated cytosine bases to cytosines within the particular dinucleotide sequence mdCpdG by catalyzing the cleaving of the methyl group as methanol. MeCP2 and MBD1 (PCM1) are first found to repress transcription by binding specifically to methylated DNA. MBD2 and MBD4 (also known as MED1) were later found to colocalize with foci of heavily methylated satellite DNA and believed to mediate the biological functions of the methylation signal. Surprisingly, MBD3 does not bind methylated DNA both in vivo and in vitro. MBD1, MBD2, MBD3, and MBD4 are found to be expressed in somatic tissues, but the expression of MBD1 and MBD2 is reduced or absent in embryonic stem cells, which are known to be deficient in MeCP1 activity. MBD4 have homology to bacterial base excision repair DNA N-glycosylases/lyases. In some microsatellite unstable tumors MBD4 is mutated at an exonic polynucleotide tract.

Supplier: Bioss

This gene encodes a member of the estrogen receptor-related receptor (ESRR) family, which belongs to the nuclear hormone receptor superfamily. All members of the ESRR family share an almost identical DNA binding domain, which is composed of two C4-type zinc finger motifs. The ESRR members are orphan nuclear receptors; they bind to the estrogen response element and steroidogenic factor 1 response element, and activate genes controlled by both response elements in the absence of any ligands. The ESRR family is closely related to the estrogen receptor (ER) family. They share target genes, co-regulators and promoters, and by targeting the same set of genes, the ESRRs seem to interfere with the ER-mediated estrogen response in various ways. It has been reported that the family member encoded by this gene functions as a transcriptional activator of DNA cytosine-5-methyltransferases 1 (Dnmt1) expression by direct binding to its response elements in the DNMT1 promoters, modulates cell proliferation and estrogen signaling in breast cancer, and negatively regulates bone morphogenetic protein 2-induced osteoblast differentiation and bone formation. Multiple alternatively spliced transcript variants have been identified, which mainly differ at the 5' end and some of which encode protein isoforms differing in the N-terminal region.

Supplier: Bioss

As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates, that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism. Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage. In the cellular response to DNA damage, the RPA complex controls DNA repair and DNA damage checkpoint activation. Through recruitment of ATRIP activates the ATR kinase a master regulator of the DNA damage response. It is required for the recruitment of the DNA double-strand break repair factors RAD51 and RAD52 to chromatin in response to DNA damage. Also recruits to sites of DNA damage proteins like XPA and XPG that are involved in nucleotide excision repair and is required for this mechanism of DNA repair. Plays also a role in base excision repair (BER) probably through interaction with UNG. Through RFWD3 may activate CHEK1 and play a role in replication checkpoint control. Also recruits SMARCAL1/HARP, which is involved in replication fork restart, to sites of DNA damage. May also play a role in telomere maintenance.

Supplier: Bioss

ErbB3 is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. ErbB3 is a membrane-bound protein which has a neuregulin binding domain but not an active kinase domain. It can therefore bind this ligand but cannot convey a signal into the cell via protein phosphorylation. However it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers including prostate, bladder and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. Isoform 2 lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported but they have not been thoroughly characterized. Defects in ERBB3 are the cause of lethal congenital contracture syndrome type 2 (LCCS2); also called Israeli Bedouin multiple contracture syndrome type A. LCCS2 is an autosomal recessive neurogenic form of a neonatally lethal arthrogryposis that is associated with atrophy of the anterior horn of the spinal cord.

Supplier: Bioss

ErbB3 is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. ErbB3 is a membrane-bound protein which has a neuregulin binding domain but not an active kinase domain. It can therefore bind this ligand but cannot convey a signal into the cell via protein phosphorylation. However it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers including prostate, bladder and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. Isoform 2 lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported but they have not been thoroughly characterized. Defects in ERBB3 are the cause of lethal congenital contracture syndrome type 2 (LCCS2); also called Israeli Bedouin multiple contracture syndrome type A. LCCS2 is an autosomal recessive neurogenic form of a neonatally lethal arthrogryposis that is associated with atrophy of the anterior horn of the spinal cord.

Supplier: Bioss

ErbB3 is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. ErbB3 is a membrane-bound protein which has a neuregulin binding domain but not an active kinase domain. It can therefore bind this ligand but cannot convey a signal into the cell via protein phosphorylation. However it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers including prostate, bladder and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. Isoform 2 lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported but they have not been thoroughly characterized. Defects in ERBB3 are the cause of lethal congenital contracture syndrome type 2 (LCCS2); also called Israeli Bedouin multiple contracture syndrome type A. LCCS2 is an autosomal recessive neurogenic form of a neonatally lethal arthrogryposis that is associated with atrophy of the anterior horn of the spinal cord.

Supplier: Bioss

Neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase. Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK.

Supplier: Bioss

DNA methylation, or the addition of methyl groups to cytosine bases in the dinucleotide CpG, is imperative to proper development and regulates gene expression. The methylation pattern involves the enzymatic processes of methylation and demethylation. The demethylation enzyme was recently found to be a mammalian protein, which exhibits demethylase activity associated to a methyl-CpG-binding domain (MBD). The enzyme is able to revert methylated cytosine bases to cytosines within the particular dinucleotide sequence mdCpdG by catalyzing the cleaving of the methyl group as methanol. MeCP2 and MBD1 (PCM1) are first found to repress transcription by binding specifically to methylated DNA. MBD2 and MBD4 (also known as MED1) were later found to colocalize with foci of heavily methylated satellite DNA and believed to mediate the biological functions of the methylation signal. Surprisingly, MBD3 does not bind methylated DNA both in vivo and in vitro. MBD1, MBD2, MBD3, and MBD4 are found to be expressed in somatic tissues, but the expression of MBD1 and MBD2 is reduced or absent in embryonic stem cells, which are known to be deficient in MeCP1 activity. MBD4 have homology to bacterial base excision repair DNA N-glycosylases/lyases. In some microsatellite unstable tumors MBD4 is mutated at an exonic polynucleotide tract.

Supplier: Bioss

The leucine-rich (LRR) repeat is a 20-30 amino acid motif that forms a hydrophobic å/∫ horseshoe fold, allowing it to accommodate several leucine residues within a tightly packed core. All LRR repeats contain a variable segment and a highly conserved segment, the latter of which accounts for 11 or 12 residues of the entire LRR motif. SLITRK5 (SLIT and NTRK-like family, member 5), also known as LRRC11 (leucine-rich repeat-containing protein 11), is a 958 amino acid single-pass type I membrane protein that contains 16 LRR repeats and belongs to the SLITRK family. Expressed at high levels in the cerebral cortex, but also present in areas of the spinal cord and medulla, SLITRK5 functions to suppress neurite outgrowth, thereby playing a regulatory role in neuronal function. The gene encoding SLITRK5 maps to human chromosome 13, which houses over 400 genes, such as BRCA2 and RB1, and comprises nearly 4% of the human genome. Trisomy 13, also known as Patau syndrome, is deadly and the few who survive past one year suffer from permanent neurologic defects, difficulty eating and vulnerability to serious respiratory infections.

Supplier: Bioss

Superoxide dismutase (SOD) is an antioxidant enzyme involved in the defense system against reactive oxygen species (ROS). SOD catalyzes the dismutation reaction of superoxide radical anion (O2-) to hydrogen peroxide, which is then catalyzed to innocuous O2 and H2O by glutathione peroxidase and catalase. Several classes of SOD have been identified. These include intracellular copper, zinc SOD (Cu, Zn-SOD/SOD-1), mitochondrial manganese SOD (Mn-SOD/SOD-2) and extracellular Cu, Zn-SOD (EC-SOD/SOD-3). SOD1 is found in all eukaryotic species as a homodimeric 32 kDa enzyme containing one each of Cu and Zn ion per subunit. The manganese containing 80 kDa tetrameric enzyme SOD2, is located in the mitochondrial matrix in close proximity to a primary endogenous source of superoxide, the mitochondrial respiratory chain. SOD3 is a heparin-binding multimer of disulfide-linked dimers, primarily expressed in human lungs, vessel walls and airways. SOD4 is a copper chaperone for superoxide dismutase (CCS), which specifically delivers Cu to copper/zinc superoxide dismutase. CCS may activate copper/zinc superoxide dismutase through direct insertion of the Cu cofactor.

Supplier: Bioss

Fanconi anemia (FA) is an autosomal recessive disorder characterized by bone marrow failure, birth defects and chromosomal instability. At the cellular level, FA is characterized by spontaneous chromosomal breakage and a unique hypersensitivity to DNA cross-linking agents. At least eight complementation groups (A-G) have been identified and six FA genes (for subtypes A, C, D2, E, F and G) have been cloned. The FA proteins lack sequence homologies or motifs that could point to a molecular function. The cellular accumulation of FA proteins, including FANCA and FANCG, is subject to regulation by TNF alpha signaling. Phosphorylation of FANC (Fanconi anemia complementation group) proteins is thought to be important for the function of the FA pathway. FANCA, also known as FACA and FANCH, associates with the Brm-related gene 1 (BRG1) product, a subunit of the SWI/SNF complex which remodels chromatin structure through a DNA-dependent ATPase activity. FANCA is mainly expressed in lymphoid tissues, testis and ovary. The amino-terminal region of the FANCA protein is required for FANCG binding, FANCC binding, nuclear localization and functional activity of the complex. The human FANCA gene maps to chromosome 16q24.3 and encodes a 1,455 amino acid protein.

Supplier: Bioss

Immunoglobulins belong to a group of related glyco proteins which make up 20% of serum proteins. Antigens and immunoglobulins react to confer immunity to individuals. Immunoglobulins have similar structures of two identical heavy chains and two identical light chains. Both the heavy chains and the light chains are divided into constant and variable regions. The constant regions have the same amino acid sequences between all the immunoglobulin classes. The variable regions have approximately 110 amino acids with high sequence variability. The amino acid sequence of the heavy chain determines the class of an immunoglobulin. The five types of immunoglobulin heavy chains are known as: IgG, IgA, IgM, IgD, and IgE. IgG is divided into four subclasses, and IgA is divided into two subclasses. In serum IgA and IgG are monomers with a single 4 polypeptide unit; while, IgM is a pen tamer. IgA may also form polymers. Kappa light chain antibody can be used for the identification of leukemias, plasmacytomas and certain non Hodgkin's lymphomas. Kappa light chain contains one immunoglobulin like domain. The EU sequence has the INV allotypic marker, Ala 45 and Val 83. The ROY sequence has the INV allotypic marker, Ala 45 and Leu 83.

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The Lyl1 gene encodes a basic helix–loop–helix transcription factor involved in T-cell acute lymphoblastic leukemia. The expression of Lyl1 is at higher levels in the majority of cases of acute myeloblastic leukemia (AML) or myelodysplastic syndrome when compared to normal bone marrow. Lyl1 is highly expressed in most AML cell lines.Lyl-1, TAL1 and TAL2 are part of a family of basic helix-loop-helix (bHLH) proteins implicated in T cell acute leukemia. TAL1, also designated SCL, is a serine phosphoprotein and basic helix-loop-helix transcription factor known to regulate embryonic hematopoiesis. TAL2 is a protein involved in T cell acute lymphoblastic leukemia through a chromosomal translocation involving TAL2 and T cell receptor ∫ chain genes. TAL2 includes a helix-loop-helix protein dimerization and DNA-binding domain that is homologous to TAL1 and Lyl-1 proto-oncogenes. Lyl-1 (lymphoblastic leukemia-derived sequence 1) is a nuclear protein. Endogenous Lyl-1 exists in complex with E2å proteins. Lyl-1 and E2å protein can form heterodimeric complexes with distinctive DNA-binding properties in hematolymphoid cells. Lyl-1 is involved in a chromosomal aberration which causes a form of T cell acute lymphoblastic leukemia (T-ALL).

Supplier: Bioss

ATF2 is a member of the ATF/CREB family of basic region leucine zipper DNA binding proteins that regulates transcription by binding to a consensus cAMP response element (CRE) in the promoter of various viral and cellular genes. Many of these genes are important in cell growth and differentiation, and in stress and immune responses. ATF2 is a nuclear protein that binds DNA as a dimer and can form dimers with members of the ATF/CREB and Jun/Fos families. It is a stronger activator as a heterodimer with cJun than as a homodimer. Several isoforms of ATF2 arise by differential splicing. The stable native full length ATF2 is transcriptionally inactive as a result of an inhibitory direct intramolecular interaction of its carboxy terminal DNA binding domain with the amino terminal transactivation domain. Following dimerization ATF2 becomes a short lived protein that undergoes ubiquitination and proteolysis, seemingly in a protein phosphatase-dependent mechanism. Stimulation of the transcriptional activity of ATF2 occurs following cellular stress induced by several genotoxic agents, inflammatory cytokines, and UV irradiation. This activation requires phosphorylation of two threonine residues in ATF2 by both JNK/SAP kinase and p38 MAP kinase. ATF2 is abundantly expressed in brain.

Supplier: Bioss

Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, ALX binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TENC1. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response. In case of filovirus infection, seems to function as a cell entry factor.

Supplier: Bioss

Superoxide dismutase (SOD) is an antioxidant enzyme involved in the defense system against reactive oxygen species (ROS). SOD catalyzes the dismutation reaction of superoxide radical anion (O2-) to hydrogen peroxide, which is then catalyzed to innocuous O2 and H2O by glutathione peroxidase and catalase. Several classes of SOD have been identified. These include intracellular copper, zinc SOD (Cu, Zn-SOD/SOD-1), mitochondrial manganese SOD (Mn-SOD/SOD-2) and extracellular Cu, Zn-SOD (EC-SOD/SOD-3). SOD1 is found in all eukaryotic species as a homodimeric 32 kDa enzyme containing one each of Cu and Zn ion per subunit. The manganese containing 80 kDa tetrameric enzyme SOD2, is located in the mitochondrial matrix in close proximity to a primary endogenous source of superoxide, the mitochondrial respiratory chain. SOD3 is a heparin-binding multimer of disulfide-linked dimers, primarily expressed in human lungs, vessel walls and airways. SOD4 is a copper chaperone for superoxide dismutase (CCS), which specifically delivers Cu to copper/zinc superoxide dismutase. CCS may activate copper/zinc superoxide dismutase through direct insertion of the Cu cofactor.

Supplier: Bioss

Guanylate cyclases belong to the adenylyl cyclase class-4/guanylyl cyclase family. There are two forms of guanylate cyclase. The soluble form, known as GCS or sGC, act as receptors for nitric oxide (NO). The membrane-bound receptor form, known as GC, are peptide hormone receptors. GCS is a cGMP-synthesizing enzyme, which is the major receptor for the neurotransmitter nitric oxide. It plays a crucial role in smooth muscle contractility, platelet reactivity and neurotransmission. GCS is a heme-containing heterodimer, consisting of one alpha subunit and one beta subunit. The heme moeity mediates NO activation, and this heme group also binds carbon monoxide (CO), which weakly stimulates the enzyme. Both NO and CO stimulation are enhanced by the allosteric activator 3-(5'-hydroxymethyl-2'furyl)-benzyl-indazole, YC-1. YC-1 can also stimulate GCS in a NO-independent manner. Both alpha and beta subunits are required for cGMP generation, and at least two isoforms exist for each subunit. Heterodimers consisting of alpha-1/beta-1 and alpha-2/beta-1 have been identified, and both display similar enzymatic activity. The distribution of the beta-2 subunit seems to be much more restricted than the beta-1 subunit, with predominant expression in kidney and liver.

Supplier: Bioss

HSPC300 (hematopoietic stem cell protein 300) is also known as probable protein BRICK1 or C3orf10 (chromosome 3 open reading frame 10) and is a 75 amino acid protein that is expressed as two isoforms and localizes to both the cytoplasm and the cytoskeleton. HSPC300 is thought to regulate cytoskeletal organization and Actin polymerization. Free HSPC300 exists as homotrimers prior to its incorporation into the WAVE complex. The WAVE complex includes five proteins, one of which is HSPC300, that regulate the ARC (Arp2/3 complex) which is responsible for Actin nucleation and is Rac 1-dependent. Because HSPC300 is a highly conserved subunit of the WAVE complex across many species, it is thought to have the same or similar functions in many different organisms. In Drosophila, the WAVE/ARC pathway may affect the development of the nervous system. HSPC300 is thought to localize to axons of the central nervous system of Drosophila embryos and thus may also be involved in axonogenesis. In addition, HSPC300 is thought to be necessary for synaptic morphogenesis by motoneurons. In mice, the knockout of the WAVE complex leads to learning and memory defects, and it is therefore hypothesized that HSPC300 may also be involved in cognitive functions. Genetic depletion of HSPC300 results in cytoskeletal abnormalities and prevents cytokinesis of cells, suggesting that decreased levels of HSPC300 may be associated with tumor suppression.

Supplier: Bioss

Superoxide dismutase (SOD) is an antioxidant enzyme involved in the defense system against reactive oxygen species (ROS). SOD catalyzes the dismutation reaction of superoxide radical anion (O2-) to hydrogen peroxide, which is then catalyzed to innocuous O2 and H2O by glutathione peroxidase and catalase. Several classes of SOD have been identified. These include intracellular copper, zinc SOD (Cu, Zn-SOD/SOD-1), mitochondrial manganese SOD (Mn-SOD/SOD-2) and extracellular Cu, Zn-SOD (EC-SOD/SOD-3). SOD1 is found in all eukaryotic species as a homodimeric 32 kDa enzyme containing one each of Cu and Zn ion per subunit. The manganese containing 80 kDa tetrameric enzyme SOD2, is located in the mitochondrial matrix in close proximity to a primary endogenous source of superoxide, the mitochondrial respiratory chain. SOD3 is a heparin-binding multimer of disulfide-linked dimers, primarily expressed in human lungs, vessel walls and airways. SOD4 is a copper chaperone for superoxide dismutase (CCS), which specifically delivers Cu to copper/zinc superoxide dismutase. CCS may activate copper/zinc superoxide dismutase through direct insertion of the Cu cofactor.

Supplier: Bioss

Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. Acts as coreceptor with CXCR4 for a restricted number of HIV isolates.

Supplier: Bioss

The autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the `pure' cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. ADCA is caused by the expansion of the CAG repeats, producing an elongated polyglutamine tract in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive generations. The function of the ataxins is not known. This locus has been mapped to chromosome 6, and it has been determined that the diseased allele contains41-81 CAG repeats, compared to 6-39 in the normal allele, and is associated with spinocerebellar ataxia type 1 (SCA1). At least two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq].

Supplier: Bioss

Cell surface protein involved in cell-cell-interactions, exocytosis of secretory granules and regulation of signal transmission. Function is isoform-specific. Alpha-type isoforms have a long N-terminus with six laminin G-like domains and play an important role in synaptic signal transmission. Alpha-type isoforms play a role in the regulation of calcium channel activity and Ca(2+)-triggered neurotransmitter release at synapses and at neuromuscular junctions. They play an important role in Ca(2+)-triggered exocytosis of secretory granules in pituitary gland. They may effect their functions at synapses and in endocrine cells via their interactions with proteins from the exocytotic machinery. Likewise, alpha-type isoforms play a role in regulating the activity of postsynaptic NMDA receptors, a subtype of glutamate-gated ion channels. Both alpha-type and beta-type isoforms may play a role in the formation or maintenance of synaptic junctions via their calcium-dependent interactions (via the extracellular domains) with neuroligin family members, CBLN1 or CBLN2. In vitro, triggers the de novo formation of presynaptic structures. May be involved in specification of excitatory synapses. Alpha-type isoforms were first identified as receptors for alpha-latrotoxin from spider venom (By similarity).

Supplier: Bioss

Ran (ras-related nuclear protein) is a small GTP binding protein belonging to the RAS superfamily that is essential for the translocation of RNA and proteins through the nuclear pore complex. The Ran protein is also involved in control of DNA synthesis and cell cycle progression. Nuclear localization of Ran requires the presence of regulator of chromosome condensation 1 (RCC1). Mutations in Ran disrupt DNA synthesis. Because of its many functions, it is likely that Ran interacts with several other proteins. Ran regulates formation and organization of the microtubule network independently of its role in the nucleus-cytosol exchange of macromolecules. Ran could be a key signaling molecule regulating microtubule polymerization during mitosis. RCC1 generates a high local concentration of Ran-GTP around chromatin which, in turn, induces the local nucleation of microtubules. Ran is an androgen receptor (AR) coactivator that binds differentially with different lengths of polyglutamine within the androgen receptor. Polyglutamine repeat expansion in the AR is linked to Kennedy's disease (X-linked spinal and bulbar muscular atrophy). Ran coactivation of the AR diminishes with polyglutamine expansion within the AR, and this weak coactivation may lead to partial androgen insensitivity during the development of Kennedy's disease.

Supplier: Bioss

Guanylate cyclases belong to the adenylyl cyclase class-4/guanylyl cyclase family. There are two forms of guanylate cyclase. The soluble form, known as GCS or sGC, act as receptors for nitric oxide (NO). The membrane-bound receptor form, known as GC, are peptide hormone receptors. GCS is a cGMP-synthesizing enzyme, which is the major receptor for the neurotransmitter nitric oxide. It plays a crucial role in smooth muscle contractility, platelet reactivity and neurotransmission. GCS is a heme-containing heterodimer, consisting of one alpha subunit and one beta subunit. The heme moeity mediates NO activation, and this heme group also binds carbon monoxide (CO), which weakly stimulates the enzyme. Both NO and CO stimulation are enhanced by the allosteric activator 3-(5'-hydroxymethyl-2'furyl)-benzyl-indazole, YC-1. YC-1 can also stimulate GCS in a NO-independent manner. Both alpha and beta subunits are required for cGMP generation, and at least two isoforms exist for each subunit. Heterodimers consisting of alpha-1/beta-1 and alpha-2/beta-1 have been identified, and both display similar enzymatic activity. The distribution of the beta-2 subunit seems to be much more restricted than the beta-1 subunit, with predominant expression in kidney and liver.

Supplier: Bioss

ATF2 is a member of the ATF/CREB family of basic region leucine zipper DNA binding proteins that regulates transcription by binding to a consensus cAMP response element (CRE) in the promoter of various viral and cellular genes. Many of these genes are important in cell growth and differentiation, and in stress and immune responses. ATF2 is a nuclear protein that binds DNA as a dimer and can form dimers with members of the ATF/CREB and Jun/Fos families. It is a stronger activator as a heterodimer with cJun than as a homodimer. Several isoforms of ATF2 arise by differential splicing. The stable native full length ATF2 is transcriptionally inactive as a result of an inhibitory direct intramolecular interaction of its carboxy terminal DNA binding domain with the amino terminal transactivation domain. Following dimerization ATF2 becomes a short lived protein that undergoes ubiquitination and proteolysis, seemingly in a protein phosphatase-dependent mechanism. Stimulation of the transcriptional activity of ATF2 occurs following cellular stress induced by several genotoxic agents, inflammatory cytokines, and UV irradiation. This activation requires phosphorylation of two threonine residues in ATF2 by both JNK/SAP kinase and p38 MAP kinase. ATF2 is abundantly expressed in brain.

Supplier: Bioss

ErbB3 is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. ErbB3 is a membrane-bound protein which has a neuregulin binding domain but not an active kinase domain. It can therefore bind this ligand but cannot convey a signal into the cell via protein phosphorylation. However it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers including prostate, bladder and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. Isoform 2 lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported but they have not been thoroughly characterized. Defects in ERBB3 are the cause of lethal congenital contracture syndrome type 2 (LCCS2); also called Israeli Bedouin multiple contracture syndrome type A. LCCS2 is an autosomal recessive neurogenic form of a neonatally lethal arthrogryposis that is associated with atrophy of the anterior horn of the spinal cord.

Supplier: Bioss

The Lyl1 gene encodes a basic helix–loop–helix transcription factor involved in T-cell acute lymphoblastic leukemia. The expression of Lyl1 is at higher levels in the majority of cases of acute myeloblastic leukemia (AML) or myelodysplastic syndrome when compared to normal bone marrow. Lyl1 is highly expressed in most AML cell lines.Lyl-1, TAL1 and TAL2 are part of a family of basic helix-loop-helix (bHLH) proteins implicated in T cell acute leukemia. TAL1, also designated SCL, is a serine phosphoprotein and basic helix-loop-helix transcription factor known to regulate embryonic hematopoiesis. TAL2 is a protein involved in T cell acute lymphoblastic leukemia through a chromosomal translocation involving TAL2 and T cell receptor ∫ chain genes. TAL2 includes a helix-loop-helix protein dimerization and DNA-binding domain that is homologous to TAL1 and Lyl-1 proto-oncogenes. Lyl-1 (lymphoblastic leukemia-derived sequence 1) is a nuclear protein. Endogenous Lyl-1 exists in complex with E2å proteins. Lyl-1 and E2å protein can form heterodimeric complexes with distinctive DNA-binding properties in hematolymphoid cells. Lyl-1 is involved in a chromosomal aberration which causes a form of T cell acute lymphoblastic leukemia (T-ALL).

Supplier: Bioss

As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates, that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism. Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage. In the cellular response to DNA damage, the RPA complex controls DNA repair and DNA damage checkpoint activation. Through recruitment of ATRIP activates the ATR kinase a master regulator of the DNA damage response. It is required for the recruitment of the DNA double-strand break repair factors RAD51 and RAD52 to chromatin in response to DNA damage. Also recruits to sites of DNA damage proteins like XPA and XPG that are involved in nucleotide excision repair and is required for this mechanism of DNA repair. Plays also a role in base excision repair (BER) probably through interaction with UNG. Through RFWD3 may activate CHEK1 and play a role in replication checkpoint control. Also recruits SMARCAL1/HARP, which is involved in replication fork restart, to sites of DNA damage. May also play a role in telomere maintenance.