Disease relevance of TCN2

• Effect of TCN2 776C>G on vitamin B12 cellular availability in end-stage renal disease patients [1].
• The MTHFD1 R653Q, SLC19A1 R27H, and TCN2 P259R polymorphisms showed no significant association with omphalocele [2].
• In genetic disorders that are characterized by congenital deficiency of TCII, intracellular Cbl deficiency occurs, resulting in an early onset of megaloblastic anemia that is sometimes accompanied by a neurologic disorder [3].
• Functional human transcobalamin II isoproteins are secreted by insect cells using the baculovirus expression system [4].
• One consensus and two atypical motifs for the c-myc ligand are located downstream and upstream, respectively, of the GC box, and this could explain the elevated plasma TCII observed in some patients with multiple myeloma, as the c-myc product is overexpressed in some myeloma cells [3].

Psychiatry related information on TCN2

• Whether his mild hypersegmentation of neutrophils and neuropathy were related to the R binder deficiency or, more likely, arose from coexisting folate deficiency and alcohol abuse, the overall picture contrasts dramatically with the severe clinical sequelae of TC II deficiency [5].
• This study compared homeless mentally ill chemical abuser (MICA) clients (n = 342), male and female, sequentially assigned to either of two modified therapeutic community programs (TC1 and TC2) and to a treatment-as-usual (TAU) control group [6].
• 20 variables were tested, 11 of them were selected as statistically significant for the prediction of total mortality: systolic blood pressure, heart rate, coronary heart disease (CHD) status (P < 0.0001), total cholesterol (TC), TC2, body mass index (BMI), BMI2, education, smoking, alcohol consumption (P < 0.01), marital status (P < 0.05) [7].

High impact information on TCN2

• Hereditary abnormal transcobalamin II previously diagnosed as congenital dihydrofolate reductase deficiency [8].
• Studies of a patient with megaloblastic anemia and an abnormal transcobalamin II [9].
• Rates of regeneration of transcobalamin II were similar in control subjects and patients with liver disease [10].
• Thirty minutes after injection of cyanocobalamin (200 ng per kilogram of body weight), total transcobalamin II (unsaturated plus cobalamin bound) declined in all 20 subjects to levels that averaged (+/- S.E.) 53.5 +/- 4.6 per cent of initial values [10].
• Increased circulating levels of transcobalamin ii in gaucher's disease [11].

Chemical compound and disease context of TCN2

• Interestingly, cycloheximide, but not TPA treatment, could induce the activity of both the TC-II and H-2Kb enhansons in F9 embryonal carcinoma cells, suggesting that these cells lack some component(s) of the protein kinase C signal transduction pathway [12].
• Also, none of the SNPs were associated with risk in subgroups of dietary methyl status or were jointly associated with colorectal cancer risk in combination with another SNP, except possibly SNPs in methionine synthase and transcobalamin II [13].
• Simultaneous addition of uniform latex particles derivatized with transferrin (0.532 micron) and transcobalamin II (0.345 micron) to leukemia L1210 cells resulted in segregated binding to individual microvilli as demonstrated by scanning electron microscopy [14].
• Small variations in TC-II affinity were recently linked to a high homocysteine level and increased frequency of neural tube defects [15].
• As 17 patients with azotemia had elevated serum TCII levels while other 3 patients with normal BUN and creatinine concentrations had serum TCII levels within the normal limits [16].

Biological context of TCN2

• METHODS: In a cross-sectional study of 732 kidney allograft recipients, patients were categorized by TCN2 776C>G genotype [17].
• BACKGROUND: Controversy exists regarding the possible associations between a single nucleotide polymorphism of the transcobalamin II encoding gene (TCN2 776C>G) and plasma levels of vitamin B(12), folate, or total homocysteine [17].
• RESULTS: The allele frequency for TCN2 776C>G was 0.46 [17].
• Small positive lod scores (Z < 1.5) were found to the following markers: ITIH1, JK and TCN2 [18].
• Transcobalamin II (TCII) is a plasma protein that binds vitamin B12 (cobalamin; Cbl) and facilitates the cellular uptake of the vitamin by receptor-mediated endocytosis [3].

Anatomical context of TCN2

• TCII did not accumulate in the SF9 cells and seemed to be constitutively secreted as observed previously in cultured human endothelial cells [4].
• The recombinant TCII cross-reacts with an antiserum to native human TCII, binds Cbl and facilitates the uptake of Cbl in eukaryotic cells by binding to the receptor for TCII-Cbl on the plasma membrane of K562 cells [4].
• RESULTS: Holo-transcobalamin II levels were normal or supranormal in all patients and showed a linear association with albumin (r = 0.205, P = 0.025) and with vitamin B12 (r = 0.778, P = 0.001), but not with age, creatinine, body mass index, tHcy, ln-tHcy, vitamin B6, plasma folate, and red blood cell folate concentration [1].
• The enhancer activity of the oligomerized SV40 TC-I and TC-II sequences has been investigated in lymphoid and non-lymphoid cell lines [12].
• This TC-II enhanson, which is identical to the kappa B motif from the kappa chain enhancer, was active in both lymphoid and non-lymphoid cells, which contrasts with the previously reported lymphoid cell specificity of the kappa B motif [12].

Associations of TCN2 with chemical compounds

• CONCLUSION: We conclude from this largest study on the subject thus far that there are no associations between allelic variants of TCN2 776C>G and plasma vitamin B(12), folate, or total homocysteine plasma levels in kidney transplant patients [17].
• Effects of TCN2 776C>G on vitamin B, folate, and total homocysteine levels in kidney transplant patients [17].
• For all study participants, total TC was associated with holoTC and number of TCN2 766C alleles; in female participants only, total TC was also associated with age, homocysteine, and cysteine [19].
• However, in contrast to the TC-II enhanson, the H-2Kb enhanson exhibits a very low activity in HeLa cells, but can be strongly induced by TPA and/or cycloheximide treatments which suggests that its cognate factor is inactivated (repressed) by an inhibitor protein [12].
• Furthermore, complex formation between the TC-IIA protein and the TC-II enhanson was efficiently competed by the kappa B motif from the kappa chain enhancer, indicating that TC-IIA is the NF-kappa B factor or a closely related protein [20].

Physical interactions of TCN2

• Transcobalamin II receptor interacts with megalin in the renal apical brush border membrane [21].
• IF-mediated import of Cbl is limited to the apical membranes of epithelial cells; it occurs via a multipurpose receptor recently termed "cubilin," and the imported Cbl is usually exported out of these cells bound to endogenous TC II [22].

Other interactions of TCN2

• A number of the exon/intron splice junctions of human TCII, TCI, and IF genes are located in homologous regions of these proteins, providing evidence that these genes have evolved by duplication of an ancestral gene [3].
• The TC2 group, which showed extra copies of the CCND1 locus and no IGH translocations or the chromosome 13q deletion, was characterized by the overexpression of genes involved in protein biosynthesis at the translational level [23].
• Stimulation with anti-CD3/CD28 antibodies increased the percentage of TC2 cells and decreased the percentage of TH2 cells [24].
• Increased TCII levels found in ACD may be explained by the higher degree of RA activity in these patients, and could also be viewed as a compensatory reaction to anaemia or reduced vitamin B12 levels [25].
• These results suggest that megalin contains a distinct single high-affinity binding site for TC II-R and their association in the native renal BBM is important for tubular reabsorption of many proteins, including TC II [21].

Analytical, diagnostic and therapeutic context of TCN2

• The purified recombinant TCII has the same molecular weight by SDS-PAGE as purified human TCII [4].
• The mean contamination of the R fraction by TC II was 14% as evaluated by gel filtration [26].
• By means of Southern blotting and sequence analysis of TC II cDNA amplified from fibroblasts of an affected child and his parents, we have identified two mutant TC II alleles, one with a gross deletion and the other with a 4 nucleotide deletion [27].
• Transcobalamin II (TCII) has been purified from Cohn fraction III of human plasma by batchwise binding to and then elution from carboxymethyl-Sephadex, affinity chromatography using photo-labile aminopropyl cobalamin coupled to activated Sephacryl S-200, and finally chromatography through carboxymethyl cellulose [28].
• TCN-1 and TCN-2 recognized Ag in tissue culture trypomastigotes but not in the amastigotes, epimastigotes, or metacyclic trypomastigotes using immunoblot assays and immunofluorescence [29].

References