Search results

Prohibitin (PHB) is an evolutionarily conserved gene that is ubiquitously expressed and which Mutations have been linked to sporadic breast cancer. PHB is thought to be a negative regulator of cell proliferation and may be a tumor suppressor. Prohibitin is expressed as two transcripts with changeable lengths of 3' untranslated region. The longer transcript is present at higher levels in proliferating tissues and cells, proposing that this longer 3' untranslated region functions as a trans-acting regulatory RNA.

Hexokinases phosphorylate glucose to produce glucose-6-phosphate, thus committing glucose to the glycolytic pathway. Alternative splicing of Glucokinase results in three tissue-specific forms of glucokinase, one found in pancreatic islet beta cells and two found in liver. The protein localizes to the outer membrane of mitochondria. In contrast to other forms of hexokinase, HK4 is not inhibited by its product glucose-6-phosphate but remains active while glucose is abundant. Mutations in this gene have been associated with non-insulin dependent diabetes mellitus (NIDDM), maturity onset diabetes of the young, type 2 (MODY2) and persistent hyperinsulinemic hypoglycemia of infancy (PHHI).

PRRX1 is part of the paired family of homeobox proteins. PRRX1 functions as a transcription co-activator, enhancing the DNA-binding activity of serum response factor, a protein required for the induction of genes by growth and differentiation factors. PRRX1 also regulates muscle creatine kinase, and therefore has a part in the establishment of diverse mesodermal muscle types. The protein binds to an A/T-rich element in the muscle creatine enhancer. Among the diseases associated with PRRX1 are agnathia-otocephaly complex, and pleomorphic liposarcoma.

Guanine Nucleotide Binding Protein Gamma Transducing 1, also known as GNGT1 is amember of the G protein gamma family. GNGT1 is implicated in various transmembrane signaling systems as a modulator or transducer. In addition GNGT1 (beta & gamma chains) is required for the GTPase activity, for replacement of GDP by GTP, and for G protein- effector interaction.

Glycerol-3-phosphate dehydrogenase 1-like protein (GPD1L) converts sn-glycerol 3-phosphate to glycerone phosphate. GPD1L is found in the cytoplasm, associated with the plasma membrane, where it binds the sodium channel, voltage-gated, type V, alpha subunit (SCN5A). Mutations in the GPD1L gene are the cause of SIDS (sudden infant death syndrome) and Brugada syndrome type 2 (an autosomal dominant tachyarrhythmia).

RING1- and YY1-binding protein (RYBP) belongs to the polycomb group (PcG). RYBP interacts with MDM2 and decreases MDM2-mediated p53 ubiquitination, which leads to stabilization of p53 and an increase in p53 activity. RYBP causes cell-cycle arrest and is involved in the p53 response to DNA damage. RYBP interacts with RING1, YY1, Caspase 10, E2F3, E2F2, Mdm2, Abl gene and CBX2. RYBP inhibits ubiquitination and subsequent degradation of TP53, and thus has a role in regulating transcription of TP53 target genes. RYBP may also be involved in the regulation of the transcription as a repressor of the transcriptional activity of E4TF1. RYBP may bind to DNA, and promote apoptosis.

Major Histocompatibility Complex Class II DR Beta 1 also known as HLA-DRB1 ia a member of the HLA class II beta chain paralogs. Molecule class II is a heterodimer consisting of an alpha (DRA) and a beta chain (DRB), both anchored in the membrane. HLA-DRB1 takes an essential part in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). Furthermore, the beta chain is approximately 26- 28 kDa. It is encoded by 6 exons. While exon one encodes the leader peptide; exons 2 and 3 encode the two extracellular domains; exon 4 encodes the transmembrane domain; and exon 5 encodes the cytoplasmic tail.

FGF-23 is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGF-23 inhibits renal tubular phosphate transport. This gene was identified by its mutations associated with autosomal dominant hypophosphatemic rickets (ADHR), an inherited phosphate wasting disorder. Abnormally high level expression of FGF23 was found in oncogenic hypophosphatemic osteomalacia (OHO), a phenotypically similar disease caused by abnormal phosphate metabolism. Mutations FGF23 have also been shown to cause familial tumoral calcinosis with hyperphosphatemia.

Neuregulin/Heregulin is a family of structurally related polypeptide growth factors which are stemmed from alternatively spliced genes (NRG1, NRG2, NRG3 and NRG4). Thus far, there are more than 14 soluble and transmembrane proteins derived from the NRG1 gene. Proteolytic processing of the extracellular domain of the transmembrane NRG1 isoforms release soluble growth factors. HRG1-b1 is comprised of an Ig domain and an EGF-like domain which is necessary for direct binding to receptor tyrosine kinases erb3 and erb4. This binding stimulates erb3 and erb4 heterodimerization with erb2, promoting intrinsic kinase activity, which results in tyrosine phosphorylation. Even though HRG1-b1 biological effects are still unclear, it has been discovered to advance motility and invasiveness of breast cancer cells which in addition might entail up-regulation of expression and function of the autocrine motility-promoting factor (AMF).

BMP2 belongs to the transforming growth factor-beta (TGFB) superfamily. Bone morphogenic protein induces bone formation. BMP2 is a candidate gene for the autosomal dominant disease of fibrodysplasia (myositis) ossificans progressiva.

Canopy FGF Signaling Regulator 4 (CNPY4) is a part of the canopy family which owns one saposin B-type domain. CNPY4 takes part in the regulation process of the cell surface expression of TLR4.

HB-EGF is an EGF related growth factor which signals via the EGF receptor, and stimulates the proliferation of SMC (smooth muscle cells), fibroblasts, epithelial cells and keratinocytes. HB-EGF is expressed in various cell types and tissues, including vascular endothelial cells and SMC, macrophages, skeletal muscle, keratinocytes and particular tumor cells. HB-EGF’s ability to explicitly bind sulfate proteoglycans is dissimilar from other EGF-like molecules, and might be related to the enhanced mitogenic activity, relative to EGF, that HB-EGF exerts on smooth muscle cells.

IGFBP1 is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein binds both insulin-like growth factors (IGFs) I and II and circulates in the plasma. Binding of this protein prolongs the half-life of the IGFs and alters their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

GARS is an (alpha)2 dimer which is a member of the class II family of tRNA synthetases. GARS is a glycyl-tRNA synthetase, one of the aminoacyl-tRNA synthetases which charge tRNAs with their cognate amino acids. GARS catalyzes the attachment of glycine to tRNA(Gly). In addition, GARS is able to produce diadenosine tetraphosphate (Ap4A), which is a universal pleiotropic signaling molecule required for cell regulation pathways, by direct condensation of two ATPs. GARS has been demonstrated to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis.

Peroxisome proliferators are non-genotoxic carcinogens which are purported to exert their effect on cells through their interaction with members of the nuclear hormone receptor family termed peroxisome proliferators activated receptors (PPARs). Nuclear hormone receptors are ligand-dependent intracellular proteins that stimulate transcription of specific genes by binding to specific DNA sequences following activation by the appropriate ligand. Studies indicate that PPARs are activated by peroxisome proliferators such as clofibric acid, nafenopin, and WY-14,643, as well as by some fatty acids.

Tumor necrosis factor receptor superfamily member 16 (NGFR) BELONGS TO the tumor necrosis factor receptor superfamily with an extensive pattern of expression in tissues such as the brain, liver, lung, and muscle. NGFR has a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, possibly by regulating RAB31 activity, and thus contributes to the regulation of insulin-dependent glucose uptake. NGFRs are low affinity receptors which can bind to NGF, BDNF, NT-3, and NT-4. NGFR mediates cell survival as well as cell death of neural cells.

Fibroblast growth factors (FGFs) comprise a family of at least eighteen structurally related proteins that are involved in a multitude of physiological and pathological cellular processes, including cell growth, differentiation, angiogenesis, wound healing and tumorgenesis. The biological activities of the FGFs are mediated by a family of type I transmembrane tyrosine kinases which undergo dimerization and autophosphorylation after ligand binding. Four distinct genes encoding closely related FGF receptors, FGF R1 - 4, are known. All four genes for FGF Rs encode proteins with an N-terminal signal peptide, three immunoglobulin (Ig)-like domains, an acid-box region containing a run of acidic residues between the IgI and IgII domains, a transmembrane domain and the split tyrosine-kinase domain. Multiple forms of FGF R1 - 3 are generated by alternative splicing of the mRNAs. A frequent splicing event involving FGF R1 and 2 results in receptors containing all three Ig domains, referred to as the a isoform, or only IgII and IgIII, referred to as the b isoform. Only the a isoform has been identified for FGF R3 and FGF R4. Additional splicing events for FGF R1 - 3, involving the C-terminal half of the IgIII domain encoded by two mutually exclusive alternative exons, generate FGF receptors with alternative IgIII domains (IIIb and IIIc). A IIIa isoform which is a secreted FGF binding protein containing only the N-terminal half of the IgIII domain plus some intron sequences has also been reported for FGF R1. Mutations in FGF R1 - 3 have been found in patients with birth defects involving craniosynostosis. The complex patterns of expression of these receptors as well as the specificity of their interactions with the various FGF ligand family members are under investigation.

Gastrokine-2 (GKN2) is expressed in the gastric mucosa. GKN2 forms a heterodimer with TFF1- disulfide linked. GKN2 interacts with TFF2.

Adiponectin is an adipocyte specific secreted protein that circulates in the plasma. It is induced during adipocyte differentiation and its secretion is stimulated by insulin. Mouse adiponectin shares about 83% amino acid identity with that human. Adiponectin plays a role in various physiological processes such as energy homeostasis and obesity. Adiponectin is reduced in obese humans, and decreased level is associated with insulin resistance and hyperinsulinemia.

Hepatocyte Growth Factor (HGF) is a multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. HGF synergizes with Interleukin-3 and GM-CSF to stimulate colony formation of hematopoietic progenitor cells in vitro and may, therefore, also modulate hematopoiesis.

SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3) which is located on chromosome 1p34.3-35, encodes for a small 93 amino acids protein. SH3BGRL3 is the newest member of thioredoxin super family, whose posttranslational altered form was recognized as TNF-alpha inhibitory protein. SH3BGRL3 may act as a regulator in all-trans retinoic acid-induced pathway and also as a modulator of glutaredoxin biological activity.

GCSF is a cytokine that controls the production, differentiation, and function of granulocytes. The active protein is found extracellularly. Three transcript variants encoding three different isoforms have been found for the GCSF gene. Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. This csf induces granulocytes.

BDNF promotes the survival of neuronal populations that are all located either in the central nervous system or directly connected to it. BDNF is a major regulator of synaptic transmission and plasticity at adult synapses in many regions of the cns. The versatility of BDNF is emphasized by its contribution to a range of adaptive neuronal responses including long-term potentiation (ltp), long-term depression (ltd), certain forms of short-term synaptic plasticity, as well as homeostatic regulation of intrinsic neuronal excitability.

Glycophorins A & B (GYPA &GYPB) are the main sialoglycoproteins of the human erythrocyte membrane which carry the antigenic determinants for the MN and Ss blood groups. Along with the M or N and S or s antigens which normally occur in all populations, approximately 40 related variant phenotypes were identified. These variants comprise all the variants of the Miltenberger complex and some isoforms of Sta, as well as Dantu, Sat, He, Mg, and deletion variants Ena, S-s-U- and Mk. GYPA is significant for the function of SLC4A1 and is necessary for high activity of SLC4A1. GYPA is involved in translocation of SLC4A1 to the plasma membrane. GYPA is also a receptor for: the influenza virus, Plasmodium falciparum erythrocyte-binding antigen 175 (EBA-175); binding of EBA-175 is dependent on sialic acid residues of the O-linked glycans and is also a receptor for Hepatitis A virus (HAV).