Disease relevance of 1810073H04Rik

• Mice bearing the Asp mutation in the serine 191 phosphorylation site are runted and anemic and display splenomegaly [1].
• Mastocytosis is often associated with a somatic point mutation in the Kit protooncogene leading to an Asp/Val substitution at position 816 in the kinase domain of this receptor [2].
• We have analyzed how the immune system generates antibodies that are specific for analogues of an epitope on the influenza virus hemagglutinin (HA) that differ solely by the presence of Asp or Gly at amino acid 225 [3].
• In contrast, poly(Arg, Gly, Asp), in which three amino acids are randomly arranged, showed neither inhibition of lung metastases nor any adhesive ability to attach to tumor cells [4].
• In longitudinal analyses, among subjects in the upper tertile of change in percent body fat, those with Asp/Asp had a larger increase in fasting and postprandial glycemia and basal EGP and a larger decrease in M and AIR than subjects with X/Gly, independent of change in obesity (all P < 0.05) [5].

Psychiatry related information on 1810073H04Rik

• In a functional presenilin-1 variant (carrying a deletion in exon 9) that is associated with familial Alzheimer's disease and which does not require this cleavage, the Asp 385 --> Ala mutation still inhibited gamma-secretase activity [6].

High impact information on 1810073H04Rik

• We have previously demonstrated that the pentapeptide Asp/Glu-Trp-Asp/Glu-Tyr-Ser/Gly is a molecular mimic of double-stranded DNA [7].
• The molecular basis for the little (lit) mouse phenotype, characterized by a hypoplastic anterior pituitary gland, is the mutation of a single nucleotide that alters Asp 60 to Gly in the growth hormone releasing factor receptor [8].
• The NOD mouse does not express I-E owing to a deletion in the promoter region of the I-E alpha-chain gene, and the sequence of NOD I-A beta-chain in the first external domain is unique with His 56 and Ser 57 replacing Pro and Asp, respectively, at these positions [9].
• The major excitatory amino acids, glutamate (Glu) and aspartate (Asp), are thought to act at three receptor subtypes in the mammalian central nervous system (CNS) [10].
• The active site "charge-relay" residues (His57, Asp102, and Ser195 of the chymotrypsin numbering system) are conserved, as well as the trypsin-specific Asp (position 189 in trypsin) [11].

Chemical compound and disease context of 1810073H04Rik

• Substitution of valine (Val) for aspartic acid (Asp) at codon 814 constitutively activates murine c-kit receptor tyrosine kinase (KIT), and Asp816Val mutation, corresponding to murine Asp814Val mutation, is found in patients with mastocytosis and acute myelocytic leukemia [12].
• This diamine- and gadolinium-substituted derivative of Abeta is shown to have enhanced in vitro binding to Alzheimer's disease (AD) amyloid plaques and increased in vivo permeability at the blood-brain barrier because of the unique Asp/Glu substitutions [13].

Biological context of 1810073H04Rik

• Taken together, these data suggest that ACF plays a crucial role, which is independent of apobec-1 expression, in cell survival, particularly during early embryonic development [14].
• Thr308 and/or Ser473 were mutated to Ala or Asp and activities of mutant PKBalpha molecules were analysed after transfection into 293 cells [15].
• Similar to other skeletal alpha-actin genes, the nucleotide sequence codes for two amino acids, Met-Cys, preceding the known N-terminal Asp of the mature protein [16].
• Lunasin is a unique 43-amino acid soybean peptide that contains at its carboxyl end: (a) nine Asp (D) residues; (b) an Arg-Gly-Asp (RGD) cell adhesion motif; and (c) a predicted helix with structural homology to a conserved region of chromatin-binding proteins [17].
• The transgenes (integrated copy number, 5-6) in the tumors developed in 55 of 56 affected transgenic mice (98%) contained at least 1 copy of the transgene that was activated by somatic point mutation at the 12th codon, from GGC (Gly) to GAC (Asp) [18].

Anatomical context of 1810073H04Rik

• Mutant acf(-)(/)(-) embryos were detectable only until the blastocyst (embryonic day 3.5 [E3.5]) stage [14].
• To examine T cell reactivity to Af antigens, T cell clones (TCC) specific to the Asp f 1 antigen, an 18-kD protein of Af, were established from the peripheral blood of three ABPA patients [19].
• Furthermore, a mutated recombinant entactin, altered to contain a Glu in place of Asp at the RGD site, provided no trophoblast cell adhesive activity [20].
• When various amino acid beta-naphthylamides were used as substrates, the preference of the secretory granule enzyme was Ala greater than Leu greater than Phe much greater than Arg much greater than Asp = Tyr [21].
• In support of these results, COS cell transfection experiments show that phosphomimetic mutation Thr-35 --> Asp or induced cellular PKC caused increased CYP1A1 targeting to MT and correspondingly lower levels to the endoplasmic reticulum [22].

Associations of 1810073H04Rik with chemical compounds

• Two independent lines of evidence demonstrate that at least two of these acidic residues are directly involved in coordinating a divalent metal ion: The substitution of Cys for Asp allows rescue of some catalytic function, whereas an alanine substitution is no longer subject to iron-induced hydroxyl radical cleavage [23].
• The proprotein convertases are all dependent on calcium for activity and all possess highly conserved subtilisin-like domains with the characteristic catalytic triad of this serine protease (ordered Asp, His, and Ser along the polypeptide chain) [24].
• The majority of TCC isolated from ABPA patients, and specific for the Asp f 1 allergen of Af, are IL-4 producing CD4+ cells of the Th2 phenotype [19].
• A human phosphorylcholine-binding myeloma protien also had Phe, Tyr, and Met at positions 32, 33, and 34, but had Asp instead of Glu at position 35 and showed a lower binding constant [25].
• One allele had a single nucleotide substitution of A to G in the NH2-terminal domain, which altered Asp to Ser at amino acid 363 [26].

Other interactions of 1810073H04Rik

• Hepatic apobec-1 complementation factor mRNA and protein abundance were significantly decreased, whereas apobec-1 mRNA and protein abundance remained unchanged [27].

Analytical, diagnostic and therapeutic context of 1810073H04Rik

• Using site-directed mutagenesis, we constructed a mutant mouse lung carbonyl reductase in which Thr-38 was replaced by Asp (T38D), and we compared kinetic properties of the mutant and wild-type enzymes in both forward and reverse reactions [28].
• Sequence analysis showed that Dub-1A encodes a 468-amino acid protein that has a molecular mass of approximately 51 kDa and that contains a putative catalytic domain (Cys, His, and Asp) conserved among DUB proteins [29].
• One mutant, M1, at position 97 (Asp to Ala) in CDR3 of the heavy chain, resulted in an 8- to 10-fold improvement in Ag binding, as assessed by ELISA [30].
• 6. In cross-sectional analyses, subjects homozygous for the Asp1057 allele (Asp/Asp) had a higher prevalence of type 2 diabetes than heterozygote individuals and subjects homozygous for the Gly1057 allele (X/Gly, P = 0.04) [5].
• Five murine IgG MAbs and two IgM MAbs were raised against the 2M fraction, and immunoprecipitation with the IgG MAb demonstrated two distinct antigens within the 2M fraction, Asp f I, and a 16 kd antigen [31].

References