Disease relevance of Pitpnm1

• While expression of either murine RdgB homolog restored the defective light response and prevented retinal degeneration in rdgB mutant flies, expressing zebrafish pl-RdgB in Drosophila rdgB2 null mutants slowed retinal degeneration without restoring the electrophysiological light response [1].

High impact information on Pitpnm1

• Here we show that RdgB protein and RdgB homologs from Saccharomyces cerevisiae, mouse, and human all possess deoxyribonucleoside triphosphate pyrophosphohydrolase activity and that all four RdgB homologs have high specificity for dHAPTP and deoxyinosine triphosphate compared with the four canonical dNTPs and several other noncanonical (d)NTPs [2].
• We hypothesized that the RdgB protein is active on 2'-deoxy-N-6-hydroxylaminopurine triphosphate (dHAPTP) as well as deoxyinosine triphosphate [2].
• Substrate Specificity of RdgB Protein, a Deoxyribonucleoside Triphosphate Pyrophosphohydrolase [2].
• Our data support a preemptive role for the RdgB homologs in excluding endogenous and exogenous modified purine dNTPs from incorporation into DNA [2].
• At the amino terminus regions of 1-372 amino acids, PITPnm formed a complex with type III PtdIns 4-kinase [3].

Biological context of Pitpnm1

• The function of RdgB is not fully understood, but the presence of a phosphatidylinositol transfer protein domain suggests a possible role in phosphatidylinositol metabolism and signaling [4].
• DRES9 encodes a phosphatidylinositol-transfer protein, suggesting that phosphatidylinositol may have a role as an intracellular messenger in vertebrate phototransduction [5].
• Because transgenic expression of M-RdgB2 does not restore the wild-type phenotype to rdgB2 mutant flies to the same extent as M-RdgB1, functional differences likely exist between the two M-RdgB homologs [6].

Anatomical context of Pitpnm1

• The transmembrane and carboxyl-terminal portions (residues 418-1242) functioned to retain the PITPnm in the Golgi vacuole [3].
• Involvement of PITPnm, a mammalian homologue of Drosophila rdgB, in phosphoinositide synthesis on Golgi membranes [3].
• PITPnm is an integral membrane protein that largely localized in close association with membranes of Golgi vacuoles and the endoplasmic reticulum (ER) [3].
• While M-RdgB1 is widely expressed, M-RdgB2 is found primarily in the retina and the dentate gyrus [4].
• RNA in situ hybridization studies performed on mouse-embryo tissue sections at various developmental stages revealed that Dres9 is expressed at very high levels in the neural retina and in the central nervous system (CNS), similar to its Drosophila counterpart [5].

Associations of Pitpnm1 with chemical compounds

• Here we report the subcellular localization of PITPnm protein and provide evidence for its involvement in phosphatidylinositol 4-phosphate (PtdIns 4-P) synthesis [3].
• Analogous to M-RdgB2, pl-RdgB protein is extracted from a retinal homogenate by guanidine and not by Triton X-100 [1].
• In the lipopolysaccharide injection model, the fluorescence signal intensity of NIR2-folate (n = 12) and of free NIR2 (n = 5) was compared between lipopolysaccharide-treated and control joints [7].

Other interactions of Pitpnm1

• Two mammalian homologs, M-RdgB1 and M-RdgB2, are known [4].

References