Disease relevance of RNF5

• Our findings further define the range of resident cells of the CNS that can express NG2 and indicate that expression of NG2 by endothelial cells is not restricted to proliferating CNS endothelial cells or to endothelial cells found in brain tumors [1].
• Competitive ELISA indicated that the antiserum reacted with this peptide but that it showed minimal ability to recognize peptides which represent the equivalent regions of the pertussis toxin-insensitive G-proteins, Gq + G11, G12, G15 + G16, GL1 (also called G14) as Gz, and well as other G-proteins [2].
• CONCLUSION: Stereotactic hematoma evacuation is clearly of value from the medicoeconomical point of view in selected patients with spontaneous putuminal hemorrhage, whose eyes are closed but open to weak stimuli (NG2) or strong stimuli (NG3) on admission [3].
• As compared with group II, group I revealed lower costs at 1 year after hemorrhage in NG2 patients, probably reflecting reduced neurologic deficits brought about by the SHE, and approximately the same costs in NG3 patients [3].
• A cDNA encoding G16 alpha, the alpha subunit of a heterotrimeric guanine nucleotide-binding protein, was expressed in Sf9 cells using recombinant baculovirus [4].
• These results indicate that RNF5 is a novel regulator of breast cancer progression through its effect on actin cytoskeletal alterations, which also affect sensitivity of breast cancer cells to cytoskeletal targeting antineoplastic agents [5].

High impact information on RNF5

• Two thymine T10 rings from different molecules stack between the C1-G16 ends of a third and a fourth hairpin helix, in a manner that suggests T-T base 'pairing' and simulates a long, 13-base-pair helix [6].
• Four monoclonal antibodies reacting with distinct human Ia antigenic determinants have been used to demonstrate the coexpression of four distinct subsets, NG1, NG2, H40+-3/4+, and DC1 H40--3/4+, in the Ia pool of DR heterozygous or homozygous B cell lines [7].
• Interaction of the NG2 chondroitin sulfate proteoglycan with type VI collagen [8].
• Immunofluorescence double labeling in frozen sections of embryonic rat shows that NG2 and type VI collagen are colocalized in structures such as the intervertebral discs and arteries of the spinal column [8].
• From some cell lines, the antibodies coprecipitate NG2 and type VI collagen, the latter appearing on SDS-PAGE as components of 140 and 250 kD under reducing conditions [8].

Chemical compound and disease context of RNF5

• The highly conserved A15-G16 dipeptide may play a role in the function of fusion domain of HIV-1 envelope glycoprotein [9].
• The mu-opioid receptor has recently been shown to stimulate phosphoinositide-specific phospholipase C via the pertussis toxin-sensitive G16 protein [10].
• Characterization of retinaldehyde dehydrogenase-2 induction in NG2-positive glia after spinal cord contusion injury [11].
• OBJECTIVES: To investigate whether a substitution of glutamine by glutamic acid at amino acid position 27 (Q/E27) and an arginine to glycine transition at amino acid 16 (R/G16) in the beta2-adrenoceptor gene are associated with lipid and lipoprotein disturbances and/or increased body weight in men [12].
• Interestingly, while the stem cell marker CD133 is expressed in these primitive neuroectodermal tumours (PNETs), the chondroitin sulphate proteoglycan neuronal/glial 2 (NG2), which appears to denote increased proliferative, but reduced migratory activity in adult gliomas, is rarely expressed [13].

Biological context of RNF5

• Concomitantly, RNF5 expression results in inhibition of cell motility [14].
• RNF5 is a RING finger protein found to be important in the growth and development of Caenorhabditis elegans [14].
• The RNF5 gene was mapped by fluorescence in situ hybridization to chromosome 6p21.31 [15].
• Cloning, expression and mapping of a novel RING-finger gene (RNF5), a human homologue of a putative zinc-finger gene from Caenorhabditis elegans [15].
• Radiation hybrid mapping further assigned RNF5 to a region proximal to the major histocompatibility complex (MHC) on chromosome 6 [15].

Anatomical context of RNF5

• Expression of RNF5 increases the cytoplasmic distribution of paxillin while decreasing its localization within focal adhesions, where it is primarily seen under normal growth [14].
• We show that fusion proteins between maltose binding protein (MBP) and human or Arabidopsis Rma1 are polyubiquitinated, when incubated with the rabbit reticulocyte or the wheat germ lysate, respectively [16].
• NG2 immunoreactivity on human brain endothelial cells [1].
• In this study, we evaluated the expression of NG2 on human brain endothelial cells derived from temporal lobe tissue resected as a treatment for intractable epilepsy [1].
• Two monoclonal antibodies, D1-12 and BT 2.2, recognizing two distinct subsets of human Ia molecules, NG1 and NG2, respectively, present in all individuals irrespective of their HLA-DR phenotype, have been used to immunoselect cell variants from the lymphoblastoid cell line Raji [17].

Associations of RNF5 with chemical compounds

• The NG2 chondroitin sulfate proteoglycan is a membrane-associated molecule of approximately 500 kD with a core glycoprotein of 300 kD [8].
• The guanosine 5'-[gamma-thio]triphosphate-activated form of G16 alpha was purified from cholate extracts of membranes from cells expressing G16 alpha, and the G-protein beta 2 and gamma 2 subunits [4].
• On poly-L-lysine-coated dishes, cell surface NG2 is associated with radial processes extending from the cell periphery [18].
• The results show that NG2/HMPG modulates integrin-mediated interactions of normal HACs with type VI collagen [19].
• These findings reveal major changes in G protein-mediated signal transduction during megakaryocytopoiesis and indicate that G16 alpha couples the thromboxane receptor to phospholipase C beta [20].

Other interactions of RNF5

• Here we demonstrate that the human homologue of RNF5 associates with the amino-terminal domain of paxillin, resulting in its ubiquitination [14].
• Coupling to both Gz and G16 was expected because close relatives of the ORL1 receptor, the opioid receptors, are known to couple productively to these G proteins [21].
• In contrast, the corresponding Co(II)-desferal conjugate directed the cleavage specific to only G sites (G12, G16, G17 and G19) [22].
• The mu, delta and kappa receptors are all capable of interacting with the pertussis toxin-sensitive G-protein alpha-subunits Gi1, Gi2, Gi3, Go1, Go2 and the pertussis toxin-insensitive Gz and G16 [23].

Analytical, diagnostic and therapeutic context of RNF5

• Using dissociated cell cultures, we found expression of NG2 on both proliferating and non-proliferating cells, at the mRNA level by reverse transcription-polymerase chain reaction analyses, and at the protein level by immunocytochemistry and immunoblotting [1].
• Two distinct subsets of human Ia molecules, called NG1 and NG2, present in all individuals irrespective of their HLA-DR phenotype, which were previously defined by their reactivity with two monoclonal hybridoma antibodies, D1--12 and D4--22, were analyzed by two-dimensional peptide mapping techniques [24].
• The degree of neurologic severity was defined on admission according to the neurologic grades (NGs) ranging from NG1 to NG5, adopted by the Japanese Cooperative Study on Stroke Surgery. The NG2 and 3 patients were randomized into 2 groups with different treatment protocols (group I, SHE; group II, conservative treatment) [3].
• The immunoprecipitation of type VI collagen does not seem to be due to recognition of the collagen by the antibodies, but rather to binding of the collagen to NG2 [8].
• Electron microscopy after rotary shadowing of native NG2 molecules indicates that this extended nonglobular domain provides a flexible connection joining the two N- and C-terminal globular regions of NG2 [25].

References