204133 Results for: "Zinc+formate&pageNo=50"

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RNA-binding protein implicated in numerous RNA metabolic processes. Catalyzes the phosphorolysis of single-stranded polyribonucleotides processively in the 3'-to-5' direction. Mitochondrial intermembrane factor with RNA-processing exoribonulease activity. Component of the mitochondrial degradosome (mtEXO) complex, that degrades 3' overhang double-stranded RNA with a 3'-to-5' directionality in an ATP-dependent manner. Required for correct processing and polyadenylation of mitochondrial mRNAs. Plays a role as a cytoplasmic RNA import factor that mediates the translocation of small RNA components, like the 5S RNA, the RNA subunit of ribonuclease P and the mitochondrial RNA-processing (MRP) RNA, into the mitochondrial matrix. Plays a role in mitochondrial morphogenesis and respiration; regulates the expression of the electron transport chain (ETC) components at the mRNA and protein levels. In the cytoplasm, shows a 3'-to-5' exoribonuclease mediating mRNA degradation activity; degrades c-myc mRNA upon treatment with IFNB1/IFN-beta, resulting in a growth arrest in melanoma cells. Regulates the stability of specific mature miRNAs in melanoma cells; specifically and selectively degrades miR-221, preferentially. Plays also a role in RNA cell surveillance by cleaning up oxidized RNAs. Binds to the RNA subunit of ribonuclease P, MRP RNA and miR-221 microRNA.

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Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteosomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors.

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Kallikrein 9, also known as Kallikrein-Like 3 (KLK-L3), is a chymotrypsin-like serine proteinase. Kallikrein 9 was discovered as the locus for kallikreins on chromosome 19 was more fully mapped and found by similarity to the other tissue kallikreins. Kallikrein 9 has been found in the ovary, thymus, testis, prostate, skin, breast and neuronal tissues and is made by many cell lines in culture. Kallikrein 9 levels in breast cancer and uterine cancer patients have been reported to drop as the disease progresses, thus hK9 might be considered a favorable prognostic marker. Different splice variants of hK9 have been reported, although it is not yet known if they produce functional proteins. The full length Kallikrein 9 encodes for a 250 amino acid protein, with a predicted mass of 27.5 kDa and a pI of 7.53. The 234 amino acid form predicts a protein of 26 kDa with a pI of 9.76 and this quite basic pI might give the shorter form a very different function or localization. The shorter sequence also diverges before the catalytic serine residue, making it unlikely to be proteolytically active. Pre-pro-kallikrein 9 has the 17 amino acid signal sequence is removed before secretion, and the Pro-kallikrein 9 is activated to Kallikrein 9 by removal of the 5 amino acid propeptide domain.

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The caspase family of cysteine proteases play a key role in apoptosis. Caspase 3 is the most extensively studied apoptotic protein among caspase family members. Caspase 3 is synthesized as inactive pro enzyme that is processed in cells undergoing apoptosis by self proteolysis and/or cleavage by other upstream proteases (e.g. Caspases 8, 9 and 10). The processed form of Caspase 3 consists of large (17kDa) and small (12kDa) subunits which associate to form an active enzyme. Caspase 3 is cleaved at Asp28 Ser29 and Asp175 Ser176. The active Caspase 3 proteolytically cleaves and activates other caspases (e.g. Caspases 6, 7 and 9), as well as relevant targets in the cells (e.g. PARP and DFF). Alternative splicing of this gene results in two transcript variants which encode the same protein. In immunohistochemical studies Caspase 3 expression has been shown to be widespread but not present in all cell types (e.g. commonly reported in epithelial cells of skin, renal proximal tubules and collecting ducts). Differences in the level of Caspase 3 have been reported in cells of short lived nature (eg germinal centre B cells) and those that are long lived (eg mantle zone B cells). Caspase 3 is the predominant caspase involved in the cleavage of amyloid beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease.

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C16orf63, also known as FLJ31153 or DKFZp686N1651, is a 174 amino acid protein that contains one LisH domain. The gene that encodes C16orf63 maps to human chromosome 16. Chromosome 16 encodes over 900 genes in approximately 90 million base pairs, makes up nearly 3% of human cellular DNA and is associated with a variety of genetic disorders. The GAN gene is located on chromosome 16 and, with mutation, may lead to giant axonal neuropathy, a nervous system disorder characterized by increasing malfunction with growth. The rare disorder Rubinstein-Taybi syndrome is also associated with chromosome 16, though through the CREBBP gene which encodes a critical CREB binding protein. Signs of Rubinstein-Taybi include mental retardation and predisposition to tumor growth and white blood cell neoplasias. Crohn's disease is a gastrointestinal inflammatory condition associated with chromosome 16 through the NOD2 gene. An association with systemic lupus erythematosis and a number of other autoimmune disorders with the pericentromeric region of chromosome 16 has led to the identification of SLC5A11 as a potential autoimmune modifier. The C16orf63 gene product has been provisionally designated C16orf63 pending further characterization.

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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.

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Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis.

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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.

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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.

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ATF1 (Activating Transcription Factor 1, TREB-36) is a member of the ATF/CREB family of basic region leucine-zipper (bZip) 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. The activation function of CRE-binding proteins may be modulated by phosphorylation of several kinases and is mediated by coactivators such as CREB-binding protein (CBP) and p300. ATF1 is a nuclear protein that binds DNA as a homodimer or as heterodimers with the inducible transcription factors CREB1 or CREM. Heterodimers appear to be stronger transcriptional activators than the homodimers. Tissue expression of ATF1 mRNA is widespread. Several isoforms of ATF1 arise by differential splicing. ATF1 mediates both Ca2+ and cAMP responses at several levels. It binds to the Tax-responsive element (TRE1) of the human T-cell lymphotropic virus type-I (HTLV1). ATF1 is detectable in metastatic melanoma cells and seems to contribute to their survival. A chimeric protein composed of the N-terminal domain of EWS (Ewing sarcoma oncogene) linked to the bZip domain of ATF1 is implicated in the rare malignant clear cell sarcoma of tendon sheath and aponeuroses (malignant melanoma of soft parts).

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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.

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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.

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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.

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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

Key regulator in endo-lysosomal trafficking. Governs early-to-late endosomal maturation, microtubule minus-end as well as plus-end directed endosomal migration and positioning, and endosome-lysosome transport through different protein-protein interaction cascades. Plays a central role, not only in endosomal traffic, but also in many other cellular and physiological events, such as growth-factor-mediated cell signaling, nutrient-transportor mediated nutrient uptake, neurotrophin transport in the axons of neurons and lipid metabolism. Also involved in regulation of some specialized endosomal membrane trafficking, such as maturation of melanosomes, pathogen-induced phagosomes (or vacuoles) and autophagosomes. Plays a role in the maturation and acidification of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis. Plays a role in the fusion of phagosomes with lysosomes. Plays important roles in microbial pathogen infection and survival, as well as in participating in the life cycle of viruses. Microbial pathogens possess survival strategies governed by RAB7A, sometimes by employing RAB7A function (e.g. Salmonella) and sometimes by excluding RAB7A function (e.g. Mycobacterium). In concert with RAC1, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. Controls the endosomal trafficking and neurite outgrowth signaling of NTRK1/TRKA. Regulates the endocytic trafficking of the EGF-EGFR complex by regulating its lysosomal degradation.

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Src (also known as pp60src) is a non receptor Tyrosine Kinase involved in signal transduction in many biological systems and implicated in the development of human tumors. There are two critical phosphorylation sites of tyrosine on Src, tyrosine 418 and tyrosine 529 (referring to human Src sequence). The tyrosine 418 is located in the catalytic domain and is one of the autophosphorylation sites. Full catalytic activity of Src requires phosphorylation of tyrosine 418. The tyrosine 529 is located near the carboxyl terminus of Src and acts as a negative regulator, in that Src is held in the inactive form through an intramolecular interaction between the SH2 domain and the carboxyl terminus when tyrosine 529 is phosphorylated by Csk. This conformation blocks phosphorylation of tyrosine 418 at the catalytic domain, thereby preventing Src activation. When tyrosine 529 is dephosphorylated, tyrosine 418 can be maximally phosphorylated and Src becomes active. Src is a proto oncogene that may play a role in the regulation of embryonic development and cell growth. Mutations in this gene could be involved in the malignant progression of colon cancer. Immunogen: Synthetic peptide (Human) derived from the region of Src that contains tyrosine 529, based on the human sequence. The sequence is conserved in mouse (tyrosine 534), chicken (tyrosine 527) and frog (tyrosine 525).

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Chemoattractant active on T-lymphocytes, monocytes, but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. SDF-1-beta(3-72) and SDF-1-alpha(3-67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on local sites. Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Inhibits CXCR4-mediated infection by T-cell line-adapted HIV-1. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of ACKR3 expressed in various cells. Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation.

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Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seem to have to effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis.

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Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play distinct roles in cells. The protein encoded by this gene is one of the PKC family members. There have been at least 12 different PKC isoforms identified in humans to date including alpha, beta I, beta II, gamma, delta, epsilon, zeta, eta, theta, iota, lambda, and mu. PKC gamma is expressed solely in the brain and spinal cord and its localization is restricted to neurons. It has been demonstrated that several neuronal functions, including long term potentiation (LTP) and long term depression (LTD), specifically require this kinase. Knockout studies in mice also suggest that this kinase may be involved in neuropathic pain development. Defects in this protein have been associated with neurodegenerative disorder spinocerebellar ataxia-14 (SCA14).

Supplier: Bioss

Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Plays an important role in defining SGOL1 localization and thereby affects sister chromatid cohesion. Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis.

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

Kallikrein 9, also known as Kallikrein-Like 3 (KLK-L3), is a chymotrypsin-like serine proteinase. Kallikrein 9 was discovered as the locus for kallikreins on chromosome 19 was more fully mapped and found by similarity to the other tissue kallikreins. Kallikrein 9 has been found in the ovary, thymus, testis, prostate, skin, breast and neuronal tissues and is made by many cell lines in culture. Kallikrein 9 levels in breast cancer and uterine cancer patients have been reported to drop as the disease progresses, thus hK9 might be considered a favorable prognostic marker. Different splice variants of hK9 have been reported, although it is not yet known if they produce functional proteins. The full length Kallikrein 9 encodes for a 250 amino acid protein, with a predicted mass of 27.5 kDa and a pI of 7.53. The 234 amino acid form predicts a protein of 26 kDa with a pI of 9.76 and this quite basic pI might give the shorter form a very different function or localization. The shorter sequence also diverges before the catalytic serine residue, making it unlikely to be proteolytically active. Pre-pro-kallikrein 9 has the 17 amino acid signal sequence is removed before secretion, and the Pro-kallikrein 9 is activated to Kallikrein 9 by removal of the 5 amino acid propeptide domain.

Supplier: Bioss

Cyclic nucleotide-gated (CNG) cation channels are heteromeric complexes made up of principal alpha and modulatory beta subunits (1,2). The alpha subunits consist of CNG1-3 and form functional cation channels by themselves (1,2). The beta subunits consist of CNG4-6 and, unlike the alpha subunits, do not form functional channels, but rather modify the properties of channels (1,2). CNG channels are essential components of olfactory and visual transduction (1,2). In olfactory neurons, CNG2, CNG4.3 and CNG5 form Ca2+ permeable channels, which open and depolarize the cell in response to cAMP (1-3). In rod photoreceptors, CNG1 and CNG4.1 combine to form Ca ion permeable channels, which give rise to a current in response to cGMP (1-3). CNG3 and CNG6 are expressed in cone receptors and may combine to form a native cGMP-activated channel (2,3). CNG channels have been implicated in other areas (4-6). CNG1 is also expressed in medium-sized and small-sized arteries, suggesting a role for CNG in the regulation of arterial blood pressure and of blood supply to different regions (4). CNG1, CNG4.1 and CNG4.2 have been detected in the rat pineal gland (5). CNG2, CNG4.3 and CNG5 are present in GT1 cell lines and may play a role in the secretion of gonadotropin-releasing hormone (6).

Supplier: Bioss

Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seem to have to effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis.

Supplier: Bioss

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease characterized by loss of motor neurons in the spinal cord. SMA is caused by deletion or loss-of-function mutations of SMN (survival of motor neuron) gene. SMN, also known as Gemin1, SMN1, SMNT and BCD541, exists as four isoforms produced by alternative splicing. SMN is oligomeric and forms a complex with Gemin2 (formerly SIP1), Gemin3 (a DEAD box RNA helicase), Gemin4, Gemin5 and Gemin6, as well as several spliceosomal snRNP proteins. The SMN complex plays an essential role in splicesomal snRNP assembly in the cytoplasm and is required for pre-mRNA splicing of the nucleus. The SMN complex is found in both the cytoplasm and the nucleus. The nuclear form is concentrated in subnuclear bodies called gems (gemini of the coiled bodies). Cytoplasmic SMN interacts with spliceosomal Sm proteins and facilitates their assembly onto U snRNAs, and nuclear SMN mediates recycling of pre-mRNA splicing factors. Nearly identical telomeric and centromeric forms of SMN encode the same protein; however, only mutations in the telomeric form are associated with the disease-state SMA. SMN is expresed in a wide variety of tissues including brain, kidney, liver, spinal cord and moderately in skeletal and cardiac muscle.

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Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC.

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Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation in breast cancer cells through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. Has also serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS.

Supplier: Bioss

Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC.

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 eight members of the recently identified Suppressor of Cytokines Signaling (SOCS) family are SOCS1, SOCS2, SOCS3, SOCS4, SOCS5, SOCS6, SOCS7, and CIS. Structurally the SOCS proteins are composed of an N- terminal region of variable length and amino acid composition, a central SH2 domain, and a C-terminal motif called the SOCS box. The SOCS proteins appear to form part of a classical negative feedback loop that regulates cytokine signal transduction. Transcription of each of the SOCS genes occurs rapidly in vitro and in vivo in response to cytokines, and once produced, the various members of the SOCS family appear to inhibit signaling in different ways. During Th1 differentiation a reduction in the association of Jak1 with the IL4 Receptor correlated with the appearance of SOCS5. SOCS5 protein was preferentially expressed in committed Th1 cells and interacted with the cytoplasmic region of the IL4 Receptor alpha chain irrespective of receptor tyrosine phosphorylation. This unconventional interaction of SOCS5 protein with IL4 Receptor resulted in the inhibition of IL4-mediated signal transducer and activator of transcription-6 activation. T cells from transgenic mice constitutively expressing SOCS5 exhibited a significant reduction of IL4-mediated Th2 development. Therefore, the induced SOCS5 protein in Th1 differentiation environment may play an important role by regulating Th1 and Th2 balance.