Disease relevance of LMOD1

• Screening 10(6) plaque-forming units from a lambda gt11 human thyroid cDNA library with a pool of 10 sera from patients with Hashimoto's thyroiditis resulted in the isolation of a clone, D1, of 292 basepairs with an open reading frame of 97 amino acids which did not share significant similarity with any known protein [1].
• The recombinant fusion protein from the original D1 clone was recognized in dot blot or Western blot assays by 4 of 19 patients with Hashimoto's thyroiditis, 3 of 9 patients with Graves' disease, and 1 of 6 patients with idiopathic myxedema; all other sera (12), including that from normal subjects, were negative [1].
• The 64kD human autoantigen D1 is expressed in slow fibers of extraocular and sternothyroid muscles as a component of myofibrils, and is not upregulated in conditions of hyperthyroidism [2].
• To evaluate the tissue-specific expression pattern of the 64kD human autoantigen D1, a tropomodulin-related protein that may be involved in thyroid-associated ophthalmopathy [2].
• We studied 26 cases of mantle cell lymphoma (MCL) for the expression of cyclins D1 and D3 [3].

Psychiatry related information on LMOD1

• Both the number of cells expressing D1 mRNA and the amount of expression per cell were measured in 15 schizophrenic, 15 bipolar disorder, and 15 normal control subjects [4].
• METHODS: Ten male soldiers were tested on days 1 (D1), 3 (D3), and 4 (D4) of a control and an experimental week that included prolonged physical work (total daily energy expenditure approximately 4,500 kcal x d(-1)), underfeeding (approximately 1,600 kcal x d(-1)), and sleep deprivation (approximately 2 h x d(-1)) [5].

High impact information on LMOD1

• Receptors for dopamine have been classified into two functional types, D1 and D2 [6].
• The presence of a D1 receptor gene restriction fragment length polymorphism will be helpful for future disease linkage studies [6].
• D2 receptors inhibit adenylyl cyclase, but D1 receptors stimulate adenylyl cyclase and activate cyclic AMP-dependent protein kinases [6].
• The goal of this review is to place the exciting advances that have occurred in our understanding of the molecular biology of the types 1, 2, and 3 (D1, D2, and D3, respectively) iodothyronine deiodinases into a biochemical and physiological context [7].
• A protein, D1, lacking the collagen-like extracellular domains of BP180 polarizes normally in 804G epithelial cells and colocalizes with other hemidesmosomal components in the plane of the basal cell surface [8].

Chemical compound and disease context of LMOD1

• Here, we constructed a mutant having D1 in which D1-Ala-344 was replaced with glycine (Gly) in cyanobacterium Synechocystis sp. PCC 6803 [9].
• No alteration in integrin beta 1D protein was observed in terms of expression level or distribution pattern, indicating that the postnatal development of cardiac hypertrophy and cardiomyopathy in these mice is unlikely associated with the stability of sarcolemmal DGC and integrin complexes [10].
• In response to all-trans-retinoic acid (RA) treatment, the human embryonal carcinoma cell line NT2/D1 exhibits a progressive decline in cyclin D1 expression beginning when the cells are committed to differentiate, but before onset of terminal neuronal differentiation [11].
• OBJECTIVE: To investigate whether polymorphisms in the genes for dopamine receptors D1 and D2 are associated with the risk of developing peak-dose dyskinesias in PD [12].
• The rhesus D1 receptor coding region was inserted into the cytomegalovirus promoter-driven expression vector pcDNA-1, and the recombinant (pcDNA-D1) was cotransfected with the selectable marker pRSVneo, conferring G418 resistance, into D1 receptor-deficient C6 glioma cells [13].

Biological context of LMOD1

• The dog equivalent of D1 cDNA was isolated by screening 10(6) plaque-forming units from a dog thyroid cDNA library using clone D1 [1].
• Human C-Lmod is located near the hypertrophic cardiomyopathy locus CMH6 on human chromosome 7q3, potentially implicating it in this disease [14].
• Biogenesis of the chloroplast-encoded D1 protein: regulation of translation elongation, insertion, and assembly into photosystem II [15].
• The D3 protein is homologous to the human D1 protein, showing an overall amino acid sequence identity of 29%, including two regions with over 60% identity [16].
• Cotransfection of a reporter gene under the control of the D1 promoter, together with the Rb gene, into Rb-deficient cell lines demonstrates stimulation of the D1 promoter by Rb, which parallels the stimulation of endogenous cyclin D1 gene expression [17].

Anatomical context of LMOD1

• Using D1 as a probe in a Northern blot revealed 3.9-kilobase (kb) transcripts in poly(A)+ RNA from normal human thyroid and extraocular muscle, but not skeletal muscle [1].
• Localization of the human 64kD autoantigen D1 to myofibrils in a subset of extraocular muscle fibers [2].
• Anti-64kD human autoantigen D1 antibodies recognize specifically a approximately 70kD polypeptide in western blots of extraocular muscle, sternothyroid muscle, and smooth muscle [2].
• The level of 1D transcript expression in these tissues decreased in the following order: thyroid (5 pg/mg total RNA) > eye muscle (3.2 pg/mg) > skeletal muscle (2.4 pg/mg) > ovary (2 pg/mg) > cerebellum (0.4 pg/mg), kidney (0.33 pg/mg), pancreas (0.27 pg/mg), spleen (0.22 pg/mg), and thymus (0.19 pg/microgram) > retina (0.016 pg/mg) [18].
• Furthermore, there was an excellent correlation between the loss of PSII activity and the loss of the D1 protein from thylakoid membranes under low light [19].

Associations of LMOD1 with chemical compounds

• Cloning and expression of the homologous domains of the receptor-like tyrosine phosphatase HPTP alpha shows that both domain 1 (D1) and domain 2 (D2) are enzymatically active [20].
• Moreover, D1 protein coprecipitates with alpha 6 integrin from extracts of HT1080 transfectants [8].
• However, deletion of a stretch of 36 amino acids located at the NH2 terminus of D1 induces an apical polarization of the protein (D1-36N) in the cell surface of 804G cells [8].
• Activities of D1 and D2 are inhibited by zinc, vanadate and EDTA and differentially susceptible to inhibition by heparin and poly(Glu4:Tyr1) [20].
• Cotranslational and post-translational assembly steps of D1 into PSII reaction center and core complexes occurred independently of photosynthetic electron transfer or trans-thylakoid proton gradient but were strongly affected by the thiol reactants DTT, NEM, and IBZ [15].

Other interactions of LMOD1

• Transcripts encoding the novel Lmod gene are present exclusively in fetal and adult heart and adult skeletal muscle, and it is here named cardiac Leiomodin (C-Lmod; HGMW-approved symbol LMOD2) [14].
• It is concluded that the D1 cDNA clone encodes an autoantigen shared by the thyroid and eye muscle [1].

Analytical, diagnostic and therapeutic context of LMOD1

• Immunofluorescence staining demonstrates that the 64kD human autoantigen D1 localizes to myofibrils in slow fibers from rat extraocular and sternothyroid muscle [2].
• We have developed a competitive reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the quantitation of 1D mRNA, which encodes a 64-kDa protein associated with thyroid-associated ophthalmopathy, in preparations of total RNA from a variety of human tissues [18].
• Molecular cloning and expression of the gene for a human D1 dopamine receptor [21].
• By immunocytochemistry, D1 and D2 had similar regional distributions in rat, monkey, and human brain, with the most intense staining in striatum, olfactory bulb, and substantia nigra [22].
• Electron microscopy demonstrated that D1 and D2 also had highly selective subcellular distributions [22].

References