Disease relevance of DOCK3

• PBP 10, an antibacterial, cell membrane-permeant rhodamine B-conjugated peptide derived from the polyphosphoinositide binding site of gelsolin, interacts selectively with both lipopolysaccharides (LPS) and lipoteichoic acid (LTA), the distinct components of gram-negative and gram-positive bacteria, respectively [1].
• BtuF is the periplasmic binding protein (PBP) in the vitamin B(12) uptake system in Escherichia coli where it is associated with the ABC transporter BtuCD [2].
• In animal studies, MDA has induced thyroid and liver neoplasms while exposure to MOCA resulted in a variety of tumors including those of the liver, mammary gland and bladder [3].
• MOCA appears to be of modest value in the treatment of bronchogenic carcinoma, particularly of the small cell type [4].
• Surprisingly, MOCAP exposure showed symptoms of neurotoxicity coupled with serum chemistry changes in the absence of any significant genomic DNA damage or brain pathology [5].

Psychiatry related information on DOCK3

• MOCA is associated with Alzheimer's disease tangles and regulates the accumulation of amyloid precursor protein and beta-amyloid [6].

High impact information on DOCK3

• Ring/methylene carbon-oxidation of MOCA accounted for 6-19% of total oxidation products in the case of the human microsomal preparations, whereas ring-oxidation of ABP accounted for less than 7% of total oxidation [7].
• These data indicate that specific inducible and constitutive cytochromes P-450 are involved in the metabolic activation and detoxification of the carcinogens ABP and MOCA [7].
• Two arylamines with known human exposure, 4-aminobiphenyl (ABP) and 4,4'-methylene-bis(2-chloroaniline) (MOCA), have been examined as substrates for 10 different purified rat hepatic cytochromes P-450 and for human liver microsomal preparations from 22 individuals [7].
• Comparison of ttGBP and MBP provides a clear example of structural adaptations by which the size of ligand binding sites can be controlled in the PBP super family [8].
• One of these is annotated as a glucose binding protein (GBP) based on its genetic linkage to genes that are homologous to an ATP-binding cassette glucose transport system, although the PBP sequence is homologous to periplasmic maltose binding proteins (MBPs) [8].

Biological context of DOCK3

• RESULTS: The amplification products were subsequently sequenced to reveal that the breakpoints lay within an intron of the dedicator of cytokinesis 3 (DOCK3) gene at the p arm breakpoint, and an intron of a novel member of the solute carrier family 9 (sodium/hydrogen exchanger) isoform 9 (SLC9A9) at the q arm [9].
• Disruption of a novel member of a sodium/hydrogen exchanger family and DOCK3 is associated with an attention deficit hyperactivity disorder-like phenotype [9].
• The modeled active sites of the L. major cpB and cpL were used to screen the Available Chemicals Directory (a database of about 150,000 commercially available compounds) for potential cysteine protease inhibitors, using DOCK3 [10].
• 4,4'-Methylenebis(2-chloroaniline) (MOCA) has considerable human occupational exposure and it induces urinary bladder tumors in the dog, a species that has been often used as a model for aromatic amine-induced urinary bladder carcinogenesis in humans [11].
• In CD rats, where MOCA is a hepatocarcinogen, less than or equal to 0.2% of an oral dose of [14C]MOCA was recovered unchanged in the urine; enzymatic hydrolysis and extraction of urinary radioactivity indicated the presence of glucuronide and sulfate conjugates [12].

Anatomical context of DOCK3

• MOCA accumulates during neuronal differentiation, and its expression enhances NGF-induced neurite outgrowth and morphological complexity [6].
• Human liver microsomes were fractionated and MOCA N-oxidation activity was monitored through the procedure [13].
• The hemolytic activities of the PBP 10 and LL37 peptides significantly increase when RBCs are osmotically swollen in hypotonic solution, indicating that these antibacterial peptides may take advantage of the more extended form of bacterial membranes in exerting their killing activities [1].
• Interaction of the gelsolin-derived antibacterial PBP 10 peptide with lipid bilayers and cell membranes [1].
• MOCA-DNA adducts have also been detected in vivo in treated rats and in exfoliated urothelium of a worker accidentally exposed to MOCA [11].

Associations of DOCK3 with chemical compounds

• Thus, the aim of this study was to detect and quantify DNA adducts in the urinary bladder of dogs exposed to MOCA and thereby provide data that could be useful for risk assessment after human exposure to MOCA [11].
• Gestodene and troleandomycin inhibited up to half of the microsomal MOCA N-hydroxylation activity but 7,8-benzoflavone showed only slight inhibition [13].
• Levels of marker activities of both P450 3A4 (nifedipine oxidation) and P450 2A6 (coumarin 7-hydroxylation) were measured in a set of human liver microsomes and both were correlated with MOCA N-oxidation rates [13].
• Castration inhibited PBP protein expression, but did not affect the expression of luminal-cell cytokeratin (CK 18) protein [14].
• Transformants containing low-affinity penicillin-binding proteins (PBP) 2x, 1a and 2b exhibited stepwise resistance to cefotaxime and penicillin [15].

Co-localisations of DOCK3

• MOCA colocalizes with N-cadherin and actin in areas of cell-cell and cell substratum contact and is expressed in neuronal processes [6].

Regulatory relationships of DOCK3

• We conclude that MOCA regulates N-cadherin-mediated cell-cell adhesion and neurite outgrowth [6].

Analytical, diagnostic and therapeutic context of DOCK3

• In addition, prophylactic cranial irradiation was administered concurrently with thoracic irradiation to 194 patients receiving CAML-HC, VCAM, or MOCA [16].
• After dermal administration of MOCA the major portion of the dose, 86.2%, remained at the application site throughout the study [17].
• The effect of multiple oral administration of MOCA, a suspect human carcinogen, was studied in the adult male rat [18].
• The nebulizer output and size distributions of aerosols of 4,4'-methylenebis(2-chloroaniline) (MOCA), benzidine, and 3,3'-dichlorobenzidine are given [19].
• Determination of benzidine, 3,3'-dimethoxybenzidine, 4-aminobiphenyl, 3,3'-dichlorobenzidine, and 4,4'-methylene-bis (2-chloroaniline) [MOCA] in soil samples surface water and groundwater by liquid chromatography with electrochemical detection [20].

References